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Successful Daily Practices of Inclusion Teachers of Children with Down Syndrome
This study asked 230 regular education teachers about their educational practices in teaching students with Down syndrome within their mainstream classes. Teachers completed surveys that asked about background experience; preparation for inclusion and the transition process; classroom information (curriculum, class arrangement, therapies, and support services); and classroom management, instruction, and behavioral strategies. Analysis of data from 120 surveys indicated that most of the students with Down syndrome attended their neighborhood schools and received some type of related services. Most of the classes had an inclusion aide who also worked with other students. Teachers considered the inclusion of children with Down syndrome successful, though there was room for improvement. Teachers found the experience challenging, rewarding, and of great value to their general education students as well as the child with Down syndrome. They noted that extra work was necessary for preparing modified class assignments, homework, and evaluation procedures. The best learning arrangements were 1:1 and small group instruction, with peer tutors, computers, and team teaching was sometimes effective. Praise was the best behavior management strategy.
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Results on the Tongue Protrusion in Downs, Following an Aspecific Antistress Drug Therapy. An Investigation on 88 Subjects
This investigation started from a consecutive series of 510 Down, selected with the exclusion of psychotic subjects. Among the 141 subjects = 27.65 % of the whole sample, who during the first consultation showed protrusion of their tongue, 88 of them (62.41%) had checked the result on this symptom following antistress drug therapy. The investigation on this subsample had the following features: as for gender they were 40 F + 48 M, with M/F = 120; the year of birth ranged between 1973 and 1993; the age at the first examination (in months) was average 40.42 +/- 35.39, with 6-183 range; distribution of the chromosomal anomalies: Four mosaicisms = 4.54%; 3 translocations = 3.41%; 80 standard trisomy 21 = 90.91%; 1 only clinical diagnosis = 1.14%; presence of the tongue protrusion: irregular in 4 = 4.65%; Frequent in 84 = 95.45%. A therapy with antistress drugs lasting average 14.73 months with range: 6-36, got the following results: 72 disappearances of the lingual protrusion = 81.82%; 8 irregular presence = 9.09%; Not varied frequent presence = 9.09%. The result is highly significant (p < 0.0001). The gender comparison suggests that there are not any meaningful differences both before and after drug therapy.
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The Free Radicals Hypothesis in Causing Dementia: High Probability Refutation in Down's Syndrome Subjects
The reduced inactivation of oxygen's free radicals is one of the hypotheses put forward to account for the onset of Alzheimer's dementia. However scarce conclusive experimental data may be to support this theory regarding human species, its refutation has not been established with any certainty either. Subjects affected by Down's syndrome have a documented increase in the enzyme superoxide-dismutase-1 and about 30% increase in the enzyme glutathione-peroxidase, both scavengers of oxygen's free radicals. For this reason Down subjects, who are less prone to cerebral palsy from prematurity and low birthweight (Cocchi, 1987; Cocchi and Branchesi, 1988), should also show a retardation in the onset of dementia, compared to normal individuals. This is not however the case as on the contrary it is regularly found that Down subjects anticipate by an average of 15 years roughly the onset of an Alzheimer type of dementia.
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PASS?
PASS? Say What? Vol. 2, No. 6, June 15, 2005, Future Planning for Families with Special Needs. Waddell & Reed, Inc.
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Language Impairment Is Associated With Decreased Plasma Coenzyme Q10 Levels in Children With Down Syndrome
Objective: Coenzyme Q10 (CoQ10) is an important endogenous cofactor for oxidative phosphorylation and potent antioxidant. Children with Down syndrome (DS) have decreased plasma CoQ10 compared with healthy children. The current follow-up report describes a relationship between CoQ10 and language impairment in children with DS. Materials & Methods: Twenty-two children with trisomy 21 previously participated in a CoQ10 dosing study. In this post hoc analysis, baseline plasma CoQ10 and cholesterol test results from the dosing study [1] were related to language impairment. Preschool Language Score (PLS-3) results for 20 participants (10 males, mean 5.1 years, range 1.7-9.3 years) were collected from their clinical records (2 were missing). Data were stratified according to PLS-3, i.e. severe (PLS-3 <70) and mild-moderate (PLS-3 =70-84) language disorder groups. P-values =0.05 were considered significant. Results: Children with severe language disorders (n=14) have significantly lower cholesterol-adjusted CoQ10 levels than children with mild-moderate disorders (n=6), i.e. 0.19 vs. 0.25 umol CoQ10/mmol cholesterol, respectively (P=0.021, Mann Whitney U test). Also a weak correlation exists between CoQ10 levels and PLS-3 data (r=0.44, P=0.05). Conclusion: These preliminary findings suggest that language impairment in children with DS may be related to a CoQ10 deficiency. Because CoQ10 supplementation has been shown to provide functional and neuroprotective benefits in neurodegenerative diseases, we hypothesize that CoQ10 supplementation may improve language skills in some children with DS.
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He Has Up Syndrome Not Down Syndrome
Book excerpt, p.48-50.
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Down's Syndrome and Cancer
Down's syndrome is a genetic disorder that is caused by trisomy of chromosome 21. Individuals with Down's syndrome have an increase risk of leukemia (10-20 fold) and a decreased incidence of solid tumors. It has been speculated that the genes on chromosome 21 are responsible for this abnormal distribution of cancer. One of such genes is copper zinc superoxide dismutase which catalyzes the dismutation of superoxide into hydrogen peroxide. Endostatin, a potent angiogenesis inhibitor, is also upregulated by trisomy 21. The paper discusses the possible role of these two genes in the occurrence of cancer in Down's syndrome subjects.
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Puttin' For Down Syndrome
The Puttin' For Down Syndrome golf tournament raised $2,500 for the Down Syndrome Association and $2,500 for the Down Syndrome Center at St. Louis Children's Hospital. But the October event in Swansea, Ill., was priceless to a special group of kids who attended their own clinic during the tourney. More than a dozen children and young adults with Down syndrome took part in the clinic, courtesy of golf pro Dan Polites with the Clinton Hills Golf Club. Along with memories of perfecting their signature swing, each player got to take home his or her own personalized golf club.
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Visioning?
Visioning? Say What? Vol. 2, No. 7, July-August, 2005, Future Planning for Families with Special Needs. Waddell & Reed, Inc.
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Exploring the Neurobiological Basis for Cognitive Problems in Down Syndrome
The hypothesis that guides our work is that each cognitive abnormality in DS is due directly or indirectly to increased expression of a specific gene(s) on chromosome 21. By discovering the responsible gene(s) it may be possible to prevent or rescue the defect. Our studies place a particular emphasis on hippocampal circuits that mediate learning and memory. We examine mouse models of DS and define changes that recapitulate those seen in DS. The Ts65Dn mouse model has a third copy of a portion of mouse chromosome 16 which is very similar to human chromosome 21 in that it contains an extra copy of about 140 homologous genes. Importantly, these mice show abnormalities in cognitive tasks mediated by hippocampus, including defects in spatial learning and memory.
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Exploring the Neurobiological Basis for Cognitive Problems in Down Syndrome. Commentary
I would like to extend my thanks to Dr. Mobley's Stanford University Down Syndrome Research team. They are moving research into uncharted territory and uncovering positive discoveries for more treatment options. (Hippocampal Long-Term Potentiation Suppressed by Increased Inhibition in the Ts65Dn Mouse, a Genetic Model of Down Syndrome. J Neurosci. 2004 Sep 15; 24(37):8153-60) This is the most exciting time in the history of DS research with the advent of a genetically engineered DS mouse, this means to add or subtract a gene or genes to/from that mouse.
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The Five Goodbyes. Mothering My Child with Down Syndrome
Book excerpts: Prologue and Molly's First Day of Kindergarten.
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Taste of the Tier helps combat cystic fibrosis
I am always happy to tell people about an opportunity to have a great night out while helping a worthy cause -- this week it's Taste of the Tier, the annual benefit for the Cystic Fibrosis Foundation of Central ...
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Robbinsdale district educations lead the way on an upward climb
Taking steps toward a cure for cystic fibrosis has led to a friendship between two teachers with poignant stories, as well as the involvement of hundreds of their students.
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CF Raccoon Hunt Set This Weekend
The annual Raccoon Hunt and Dog Show benefiting the Cystic Fibrosis Foundation is set for Friday and Saturday in Atlanta, said Ashley Jamison, special events coordinator for the foundation's Tyler office.
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Norwich man receives award for advocacy of cystic fibrosis patients
NORWICH -- By his own account, Hal Soloff has been many things in his life; teacher, attorney, political activist and world-traveler, just to name a few.
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Cystic Fibrosis - Topix.net
News on Cystic Fibrosis continually updated from thousands of sources around the net.
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Cystic Fibrosis - Topix.net
News on Cystic Fibrosis continually updated from thousands of sources around the net.
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A night at The Bluebird
Tammy Cochran brought a taste of Nashville night life to the Geneva Veterans of Foreign Wars hall Friday night.
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Copernicus Therapeutics helps Parkinson's researcher
Categories: Breaking News University of Kentucky researcher David Yurek is using technology from Copernicus Therapeutics Inc.
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Phase II Cystic Fibrosis Study Closes Enrollment
SYDNEY, Australia, March 1 /Xinhua-PRNewswire-FirstCall/ -- Pharmaxis Ltd Array The study has entered 25 subjects.
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Cystic Fibrosis Leads Mother To Write Children's Book
Cystic fibrosis is an inherited disease and until the 1980s, most deaths occurred in children and teenagers.
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Cystic Fibrosis Program at New York-Presbyterian Among Nation's Best
The Cystic Fibrosis Program at NewYork-Presbyterian Hospital/Columbia University Medical Center and Morgan Stanley Children's Hospital of NewYork-Presbyterian is among the nation's best, according to an ...
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"physical medicine rehabilitation" - Yahoo! News Search Results
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Combo Treatment Helps Heal Overused, Aching Joints
In a recent study published in Physical Medicine & Rehabilitation, Mayo Clinic researchers reported that the combination of tenotomy and platelet rich plasma injections produced significant improvement in patients with long-standing tendon injuries.
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Combination of tenotomy and PRP injections can treat tendon disorders
Many athletes know the frustration of being sidelined by tendon disorders, like Achilles tendinitis and tennis elbow. In recent years, doctors have begun treating overused tendons with regenerative therapies that jump-start the body's own healing process. One technique, a tenotomy, uses repeated needlesticks to break up scar tissue in the tendon, prompting the body's own cells to begin the ...
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Sutter Health Salutes Physicians Named as Top Doctors in Marin and San Francisco
Almost 250 physicians at California Pacific Medical Center, Sutter Pacific Medical Foundation, and Novato Community Hospital - all part of the Sutter Health network - have been named on the prestigious list of [415] Top Doctors 2012 by Marin Magazine.
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The Methodist Hospital now offers advanced rehabilitation system for treatment of foot drop
The Methodist Hospital Outpatient Rehabilitation Center now offers an advanced rehabilitation system for the treatment of foot drop in people with mobility issues caused by stroke, traumatic brain injury, multiple sclerosis, cerebral palsy and spinal cord injury.
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Dr. Bruce E. Becker Appointed Director of Aquatic Health Benefit Research by National Swimming Pool Foundation
COLORADO SPRINGS, Colo. , Jan. 12, 2012 /PRNewswire/ -- The National Swimming Pool Foundation® (NSPF®) board of directors has appointed Bruce Erhart Becker, MD, MS as Director of Aquatic Health Benefit ...
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Colin Hoobler: You don't need a gym to work your hamstrings
Chondromalacia (softened bone) is a commonly used medical term to describe chronic knee pain associated with the front part of your knees, usually made worse with certain activities (negotiating stairs, kneeling, prolonged walking).
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The Methodist Hospital in Houston Is First to Offer New Device to Improve Walking
A new device help people with foot drop walk.
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Senior center dance coming Jan. 7
Here is your chance to take your turn on the floor! Waltz, tango or cha-cha the night away to music by The Old Smoothies. Socialize and enjoy refreshments provided by the National Charity League, Inc. Singles and couples welcome. Join us on Saturday,...
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Colin Hoobler: Deal with source of pain, not just the symptoms
Dear Colin: I've had chronic low back/leg pain for 10 years that has frustrated my doctor and others he's referred me to for help.
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Obesity is nationwide threat to health
There are 1 billion overweight individuals worldwide who add to society’s modern epidemic: obesity. The Centers for Disease Control and Prevention (CDC) has tracked the cumulative weight gain of our society by state.
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physiatrist - Yahoo! News Search Results
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Greenwich Docs Included in Castle Connolly New York Top Doctors Guide, 15th edition
12 Specialists from ONS included in New York Area Medical Guide BookGREENWICH, CT (PRWEB) January 27, 2012 Twelve physicians from Orthopaedic and Neurosurgery Specialists (ONS) on Valley Drive are included in the latest edition of Castle Connolly Top Doctors, New York Metro Area guidebook. The resource directory, which is in its fifteenth edition, is a guide to finding the top primary care and ...
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BUSINESS PLAYERS: Good Shepherd names medical director of neurosciences
Soofia Khan
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Region in a minute
ANDOVER - The last day for Andover residents to register to vote in the presidential primary is Feb. 15. The primary will be held Tuesday, March 6. Polling hours are from 7 a.m to 8:00 p.m. The town clerk's office will be open until 8 p.m. on Feb. 15 for voter registration. The last day to apply for an absentee ballot is noon March 5th. Absentee ballots are now available at the Town Clerk's ...
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Vycor Medical's VBAS Granted Regulatory Clearance in China; Opening Order of $170,000 Shipped
BOCA RATON, Fla. , Jan. 17, 2012 /PRNewswire/ -- Vycor Medical, Inc. (OTCBB: VYCO.OB - News) ("Vycor") today announced that its ViewSite Brain Access System ("VBAS") has received clearance from ...
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Experts torn on Penguins captain Crosby's injury
Concussion and spine experts don't know what to make of Penguins center Sidney Crosby's "soft tissue" neck injury.
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What is spinal stenosis, and how serious is it?
Spinal stenosis is a narrowing of the spinal canal that can — but does not always — cause pain in the legs and other problems.
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Dr. Bruce E. Becker Appointed Director of Aquatic Health Benefit Research by National Swimming Pool Foundation
COLORADO SPRINGS, Colo. , Jan. 12, 2012 /PRNewswire/ -- The National Swimming Pool Foundation® (NSPF®) board of directors has appointed Bruce Erhart Becker, MD, MS as Director of Aquatic Health Benefit ...
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Hiran sports brand new Macho look
Kolkata, Jan 17 : ‘Work is Worship’ is an idiom that now aptly fits Tollywood actor Hiran Chatterjee.
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Vycor Medical, Inc. Acquires Sight Science Limited, a Highly Complementary Business for NovaVision
BOCA RATON, Fla. , Jan. 10, 2012 /PRNewswire/ -- Vycor Medical, Inc. ("Vycor") (OTCBB: VYCO.OB - News) today announced that its wholly owned subsidiary, NovaVision Inc. ("NovaVision") has acquired ...
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New Year’s fitness hype may not last
by Sammy Caiola ... ;
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physiatry - Yahoo! News Search Results
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Diederich Healthcare Expands Medical Malpractice Coverage to New Jersey Physicians
Diederich Healthcare, a division of Diederich Insurance Agency, LLC, a leading provider of physician professional liability insurance, has announced that the agency has expanded its coverage area to include physicians practicing in the state of New Jersey.Carbondale, IL (PRWEB) February 02, 2012 Diederich Healthcare, a division of Diederich Insurance Agency, LLC, a leading provider of medical ...
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Diederich Healthcare Expands Med Mal Coverage to New Jersey
Diederich Healthcare has expanded its coverage area to include physicians practicing in New Jersey. The expansion offers additional coverage options to physicians in the state through Positive Physicians Insurance Exchange (PPIX), a fully admitted New Jersey carrier. “This expansion is …
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Greenwich Docs Included in Castle Connolly New York Top Doctors Guide, 15th edition
12 Specialists from ONS included in New York Area Medical Guide BookGREENWICH, CT (PRWEB) January 27, 2012 Twelve physicians from Orthopaedic and Neurosurgery Specialists (ONS) on Valley Drive are included in the latest edition of Castle Connolly Top Doctors, New York Metro Area guidebook. The resource directory, which is in its fifteenth edition, is a guide to finding the top primary care and ...
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Yahoo! Health News
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Dealing With Head Lice
SUNDAY, Feb. 5 (HealthDay News) -- Although there is a stigma associated with having head lice, infestations with these small insects are common and nothing to be ashamed of, according to Dr. Hannah Chow-Johnson, a pediatrician at Loyola Universit...
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Olympus to hold shareholder meeting on April 20
TOKYO (Reuters) - Japan's troubled Olympus Corp said on Sunday it will hold an extraordinary shareholders meeting on April 20, when it is expected to seek approval of a new management team. The maker of cameras and medical equipment is struggl...
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Safe Social Networking Tips for Teens
SUNDAY, Feb. 5 (HealthDay News) -- More than 60 percent of American teens have at least one profile on a social networking site, and many spend more than two hours a day on social networking sites, according to the American Academy of Child and Ad...
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Parents urge more tests as twitches spread at New York school
LE ROY, New York (Reuters) - State health officials have added three more names to a growing list of students in this working-class town who are experiencing mysterious tics and twitching, while authorities on Saturday sought to assure parents the...
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Cancer survivors line up as opponents in Super Bowl
INDIANAPOLIS (Reuters) - There can only be one winner in Sunday's Super Bowl but for two opposing players, a bigger battle has already been won, victory over cancer. New York Giants linebacker Mark Herzlich and New England Patriots offensive l...
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Some former Komen supporters can't forgive, forget
When Dorothy Twinney first saw a Race for the Cure walk for breast cancer — "a sea of pink" traveling through her hometown of Plymouth, Mich. — she was so moved she sat in her car and wept.
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Don't Fumble Your Diet on Super Bowl Sunday
SATURDAY, Feb. 4 (HealthDay News) -- All the food and beverages served at Super Bowl parties can make it a challenging day for people who made a New Year's resolution to lose weight.
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Winter Can Pose Hazards for Seniors
SATURDAY, Feb. 4 (HealthDay News) -- Winter weather can be challenging for some seniors, especially those with mobility or other health issues.
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Germany wages war against 'burnout'
Germany, holding up better than its eurozone partners in the current debt crisis, is battling the increasingly widespread phenomenon of "burnout" which it says is costing its economy billions of euros (dollars) each year.
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Breastfeeding tied to stronger lungs, less asthma
NEW YORK (Reuters Health) - Kids who were breastfed as babies may have better lung function, and a lower risk of asthma, than those who were formula-fed, two new reports suggest. Researchers said that past studies have found conflicting results wh...
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Allergan to rely less on U.S. for sales, Asia key
(Reuters) - Allergan Inc, maker of wrinkle treatment Botox, eye drops and obesity treatments, said it will rely less on the United States for revenue in coming years as its products gain wider acceptance in Asia, particularly China. The company on...
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Insight: In PIP implant scandal, a ragged safety net exposed
LONDON (Reuters) - In June 2000, when American medical regulators posted a warning letter on the Internet about problems at a breast-implant maker in southern France, French authorities didn't pay much attention. A U.S. Food and Drug Administr...
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Maine girl bouncing back after 6-organ transplant
A 9-year-old Maine girl is home from a Boston hospital healthy, active and with high hopes — and a new stomach, liver, spleen, small intestine, pancreas, and part of an esophagus to replace the ones that were being choked by a huge tumor.
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Health Tip: Prepare for Breast-feeding
(HealthDay News) -- Preparations for successful breast-feeding begin during pregnancy.
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Health Tip: Teach Your Toddler Good Behavior
(HealthDay News) -- Toddler tantrums can challenge even the most patient parent, but being firm and consistent can help you discipline your toddler in an effective, loving way.
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Walgreen sales hit by exit from Express Scripts
(Reuters) - Walgreen Co is being hit by its withdrawal from the Express Scripts Inc pharmacy network and by a much-weaker-than-expected flu season, leading it to temper its expectations for the number of prescriptions it will fill this year. Walgr...
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Malaria death toll possibly twice as high
Malaria may be killing around twice as many people as experts previously thought, and it could also be hitting older children and adults — long considered the least susceptible — a new study suggests.
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Bloomberg pledges $250,000 to Planned Parenthood
NEW YORK (Reuters) - Billionaire New York City Mayor Michael Bloomberg pledged on Thursday to give $250,000 of his own money to the Planned Parenthood Federation of America after breast cancer charity Susan G. Komen for the Cure withdrew funding f...
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Senators urge Komen to reconsider funding decision
WASHINGTON (Reuters) - Some two dozen Democrats in the Senate on Thursday called on breast cancer charity Susan G. Komen for the Cure to reconsider its decision to cut off funding to the Planned Parenthood Federation of America. Senators Frank Lau...
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Strong jobs report pushes Nasdaq to 11-year high
NEW YORK (Reuters) - U.S. stocks rose on Friday, propelling the Nasdaq index to an 11-year high, after January's U.S. employment report sailed past expectations, boosting hopes the world's largest economy has turned a corner. The broad-bas...
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New map pinpoints Lyme disease risk areas
Researchers who spent three years dragging sheets of fabric through the woods to snag ticks have created a detailed map they claim could improve prevention, diagnosis and treatment of Lyme disease.
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Nerve disorder does not recur after later vaccines: study
NEW YORK (Reuters Health) - Despite concerns by some that vaccines might cause a crippling nerve disorder called Guillain-Barré syndrome, a new study finds that people who receive vaccines after previously having been diagnosed with the condition ...
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Jobs strength lifts Nasdaq to 11-year high
NEW YORK (Reuters) - A surge in hiring last month lifted U.S. stocks on Friday, with the Nasdaq index hitting an 11-year high, as the data boosted hopes the world's largest economy has turned a corner. The broad-based gains also sent the Dow J...
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Breast cancer fund to restore funding after outcry
A major US breast cancer foundation Friday reversed its decision to stop funding Planned Parenthood after outcry over the move sparked a political and fundraising backlash by women's health advocates.
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Malaria kills twice as many as thought: study
LONDON (Reuters) - Malaria kills more than 1.2 million people worldwide a year, nearly twice as many as previously thought, according to new research published on Friday that questions years of assumptions about the mosquito-borne disease. Past st...
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Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
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Yahoo! Health News
|
-
Dealing With Head Lice
SUNDAY, Feb. 5 (HealthDay News) -- Although there is a stigma associated with having head lice, infestations with these small insects are common and nothing to be ashamed of, according to Dr. Hannah Chow-Johnson, a pediatrician at Loyola Universit...
-
Olympus to hold shareholder meeting on April 20
TOKYO (Reuters) - Japan's troubled Olympus Corp said on Sunday it will hold an extraordinary shareholders meeting on April 20, when it is expected to seek approval of a new management team. The maker of cameras and medical equipment is struggl...
-
Safe Social Networking Tips for Teens
SUNDAY, Feb. 5 (HealthDay News) -- More than 60 percent of American teens have at least one profile on a social networking site, and many spend more than two hours a day on social networking sites, according to the American Academy of Child and Ad...
-
Parents urge more tests as twitches spread at New York school
LE ROY, New York (Reuters) - State health officials have added three more names to a growing list of students in this working-class town who are experiencing mysterious tics and twitching, while authorities on Saturday sought to assure parents the...
-
Cancer survivors line up as opponents in Super Bowl
INDIANAPOLIS (Reuters) - There can only be one winner in Sunday's Super Bowl but for two opposing players, a bigger battle has already been won, victory over cancer. New York Giants linebacker Mark Herzlich and New England Patriots offensive l...
-
Some former Komen supporters can't forgive, forget
When Dorothy Twinney first saw a Race for the Cure walk for breast cancer — "a sea of pink" traveling through her hometown of Plymouth, Mich. — she was so moved she sat in her car and wept.
-
Don't Fumble Your Diet on Super Bowl Sunday
SATURDAY, Feb. 4 (HealthDay News) -- All the food and beverages served at Super Bowl parties can make it a challenging day for people who made a New Year's resolution to lose weight.
-
Winter Can Pose Hazards for Seniors
SATURDAY, Feb. 4 (HealthDay News) -- Winter weather can be challenging for some seniors, especially those with mobility or other health issues.
-
Germany wages war against 'burnout'
Germany, holding up better than its eurozone partners in the current debt crisis, is battling the increasingly widespread phenomenon of "burnout" which it says is costing its economy billions of euros (dollars) each year.
-
Breastfeeding tied to stronger lungs, less asthma
NEW YORK (Reuters Health) - Kids who were breastfed as babies may have better lung function, and a lower risk of asthma, than those who were formula-fed, two new reports suggest. Researchers said that past studies have found conflicting results wh...
-
Allergan to rely less on U.S. for sales, Asia key
(Reuters) - Allergan Inc, maker of wrinkle treatment Botox, eye drops and obesity treatments, said it will rely less on the United States for revenue in coming years as its products gain wider acceptance in Asia, particularly China. The company on...
-
Insight: In PIP implant scandal, a ragged safety net exposed
LONDON (Reuters) - In June 2000, when American medical regulators posted a warning letter on the Internet about problems at a breast-implant maker in southern France, French authorities didn't pay much attention. A U.S. Food and Drug Administr...
-
Maine girl bouncing back after 6-organ transplant
A 9-year-old Maine girl is home from a Boston hospital healthy, active and with high hopes — and a new stomach, liver, spleen, small intestine, pancreas, and part of an esophagus to replace the ones that were being choked by a huge tumor.
-
Health Tip: Prepare for Breast-feeding
(HealthDay News) -- Preparations for successful breast-feeding begin during pregnancy.
-
Health Tip: Teach Your Toddler Good Behavior
(HealthDay News) -- Toddler tantrums can challenge even the most patient parent, but being firm and consistent can help you discipline your toddler in an effective, loving way.
-
Walgreen sales hit by exit from Express Scripts
(Reuters) - Walgreen Co is being hit by its withdrawal from the Express Scripts Inc pharmacy network and by a much-weaker-than-expected flu season, leading it to temper its expectations for the number of prescriptions it will fill this year. Walgr...
-
Malaria death toll possibly twice as high
Malaria may be killing around twice as many people as experts previously thought, and it could also be hitting older children and adults — long considered the least susceptible — a new study suggests.
-
Bloomberg pledges $250,000 to Planned Parenthood
NEW YORK (Reuters) - Billionaire New York City Mayor Michael Bloomberg pledged on Thursday to give $250,000 of his own money to the Planned Parenthood Federation of America after breast cancer charity Susan G. Komen for the Cure withdrew funding f...
-
Senators urge Komen to reconsider funding decision
WASHINGTON (Reuters) - Some two dozen Democrats in the Senate on Thursday called on breast cancer charity Susan G. Komen for the Cure to reconsider its decision to cut off funding to the Planned Parenthood Federation of America. Senators Frank Lau...
-
Strong jobs report pushes Nasdaq to 11-year high
NEW YORK (Reuters) - U.S. stocks rose on Friday, propelling the Nasdaq index to an 11-year high, after January's U.S. employment report sailed past expectations, boosting hopes the world's largest economy has turned a corner. The broad-bas...
-
New map pinpoints Lyme disease risk areas
Researchers who spent three years dragging sheets of fabric through the woods to snag ticks have created a detailed map they claim could improve prevention, diagnosis and treatment of Lyme disease.
-
Nerve disorder does not recur after later vaccines: study
NEW YORK (Reuters Health) - Despite concerns by some that vaccines might cause a crippling nerve disorder called Guillain-Barré syndrome, a new study finds that people who receive vaccines after previously having been diagnosed with the condition ...
-
Jobs strength lifts Nasdaq to 11-year high
NEW YORK (Reuters) - A surge in hiring last month lifted U.S. stocks on Friday, with the Nasdaq index hitting an 11-year high, as the data boosted hopes the world's largest economy has turned a corner. The broad-based gains also sent the Dow J...
-
Breast cancer fund to restore funding after outcry
A major US breast cancer foundation Friday reversed its decision to stop funding Planned Parenthood after outcry over the move sparked a political and fundraising backlash by women's health advocates.
-
Malaria kills twice as many as thought: study
LONDON (Reuters) - Malaria kills more than 1.2 million people worldwide a year, nearly twice as many as previously thought, according to new research published on Friday that questions years of assumptions about the mosquito-borne disease. Past st...
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Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
|
Yahoo! Health News
|
-
Dealing With Head Lice
SUNDAY, Feb. 5 (HealthDay News) -- Although there is a stigma associated with having head lice, infestations with these small insects are common and nothing to be ashamed of, according to Dr. Hannah Chow-Johnson, a pediatrician at Loyola Universit...
-
Olympus to hold shareholder meeting on April 20
TOKYO (Reuters) - Japan's troubled Olympus Corp said on Sunday it will hold an extraordinary shareholders meeting on April 20, when it is expected to seek approval of a new management team. The maker of cameras and medical equipment is struggl...
-
Safe Social Networking Tips for Teens
SUNDAY, Feb. 5 (HealthDay News) -- More than 60 percent of American teens have at least one profile on a social networking site, and many spend more than two hours a day on social networking sites, according to the American Academy of Child and Ad...
-
Parents urge more tests as twitches spread at New York school
LE ROY, New York (Reuters) - State health officials have added three more names to a growing list of students in this working-class town who are experiencing mysterious tics and twitching, while authorities on Saturday sought to assure parents the...
-
Cancer survivors line up as opponents in Super Bowl
INDIANAPOLIS (Reuters) - There can only be one winner in Sunday's Super Bowl but for two opposing players, a bigger battle has already been won, victory over cancer. New York Giants linebacker Mark Herzlich and New England Patriots offensive l...
-
Some former Komen supporters can't forgive, forget
When Dorothy Twinney first saw a Race for the Cure walk for breast cancer — "a sea of pink" traveling through her hometown of Plymouth, Mich. — she was so moved she sat in her car and wept.
-
Don't Fumble Your Diet on Super Bowl Sunday
SATURDAY, Feb. 4 (HealthDay News) -- All the food and beverages served at Super Bowl parties can make it a challenging day for people who made a New Year's resolution to lose weight.
-
Winter Can Pose Hazards for Seniors
SATURDAY, Feb. 4 (HealthDay News) -- Winter weather can be challenging for some seniors, especially those with mobility or other health issues.
-
Germany wages war against 'burnout'
Germany, holding up better than its eurozone partners in the current debt crisis, is battling the increasingly widespread phenomenon of "burnout" which it says is costing its economy billions of euros (dollars) each year.
-
Breastfeeding tied to stronger lungs, less asthma
NEW YORK (Reuters Health) - Kids who were breastfed as babies may have better lung function, and a lower risk of asthma, than those who were formula-fed, two new reports suggest. Researchers said that past studies have found conflicting results wh...
-
Allergan to rely less on U.S. for sales, Asia key
(Reuters) - Allergan Inc, maker of wrinkle treatment Botox, eye drops and obesity treatments, said it will rely less on the United States for revenue in coming years as its products gain wider acceptance in Asia, particularly China. The company on...
-
Insight: In PIP implant scandal, a ragged safety net exposed
LONDON (Reuters) - In June 2000, when American medical regulators posted a warning letter on the Internet about problems at a breast-implant maker in southern France, French authorities didn't pay much attention. A U.S. Food and Drug Administr...
-
Maine girl bouncing back after 6-organ transplant
A 9-year-old Maine girl is home from a Boston hospital healthy, active and with high hopes — and a new stomach, liver, spleen, small intestine, pancreas, and part of an esophagus to replace the ones that were being choked by a huge tumor.
-
Health Tip: Prepare for Breast-feeding
(HealthDay News) -- Preparations for successful breast-feeding begin during pregnancy.
-
Health Tip: Teach Your Toddler Good Behavior
(HealthDay News) -- Toddler tantrums can challenge even the most patient parent, but being firm and consistent can help you discipline your toddler in an effective, loving way.
-
Walgreen sales hit by exit from Express Scripts
(Reuters) - Walgreen Co is being hit by its withdrawal from the Express Scripts Inc pharmacy network and by a much-weaker-than-expected flu season, leading it to temper its expectations for the number of prescriptions it will fill this year. Walgr...
-
Malaria death toll possibly twice as high
Malaria may be killing around twice as many people as experts previously thought, and it could also be hitting older children and adults — long considered the least susceptible — a new study suggests.
-
Bloomberg pledges $250,000 to Planned Parenthood
NEW YORK (Reuters) - Billionaire New York City Mayor Michael Bloomberg pledged on Thursday to give $250,000 of his own money to the Planned Parenthood Federation of America after breast cancer charity Susan G. Komen for the Cure withdrew funding f...
-
Senators urge Komen to reconsider funding decision
WASHINGTON (Reuters) - Some two dozen Democrats in the Senate on Thursday called on breast cancer charity Susan G. Komen for the Cure to reconsider its decision to cut off funding to the Planned Parenthood Federation of America. Senators Frank Lau...
-
Strong jobs report pushes Nasdaq to 11-year high
NEW YORK (Reuters) - U.S. stocks rose on Friday, propelling the Nasdaq index to an 11-year high, after January's U.S. employment report sailed past expectations, boosting hopes the world's largest economy has turned a corner. The broad-bas...
-
New map pinpoints Lyme disease risk areas
Researchers who spent three years dragging sheets of fabric through the woods to snag ticks have created a detailed map they claim could improve prevention, diagnosis and treatment of Lyme disease.
-
Nerve disorder does not recur after later vaccines: study
NEW YORK (Reuters Health) - Despite concerns by some that vaccines might cause a crippling nerve disorder called Guillain-Barré syndrome, a new study finds that people who receive vaccines after previously having been diagnosed with the condition ...
-
Jobs strength lifts Nasdaq to 11-year high
NEW YORK (Reuters) - A surge in hiring last month lifted U.S. stocks on Friday, with the Nasdaq index hitting an 11-year high, as the data boosted hopes the world's largest economy has turned a corner. The broad-based gains also sent the Dow J...
-
Breast cancer fund to restore funding after outcry
A major US breast cancer foundation Friday reversed its decision to stop funding Planned Parenthood after outcry over the move sparked a political and fundraising backlash by women's health advocates.
-
Malaria kills twice as many as thought: study
LONDON (Reuters) - Malaria kills more than 1.2 million people worldwide a year, nearly twice as many as previously thought, according to new research published on Friday that questions years of assumptions about the mosquito-borne disease. Past st...
|
|
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Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
|
Yahoo! Health News
|
-
Dealing With Head Lice
SUNDAY, Feb. 5 (HealthDay News) -- Although there is a stigma associated with having head lice, infestations with these small insects are common and nothing to be ashamed of, according to Dr. Hannah Chow-Johnson, a pediatrician at Loyola Universit...
-
Olympus to hold shareholder meeting on April 20
TOKYO (Reuters) - Japan's troubled Olympus Corp said on Sunday it will hold an extraordinary shareholders meeting on April 20, when it is expected to seek approval of a new management team. The maker of cameras and medical equipment is struggl...
-
Safe Social Networking Tips for Teens
SUNDAY, Feb. 5 (HealthDay News) -- More than 60 percent of American teens have at least one profile on a social networking site, and many spend more than two hours a day on social networking sites, according to the American Academy of Child and Ad...
-
Parents urge more tests as twitches spread at New York school
LE ROY, New York (Reuters) - State health officials have added three more names to a growing list of students in this working-class town who are experiencing mysterious tics and twitching, while authorities on Saturday sought to assure parents the...
-
Cancer survivors line up as opponents in Super Bowl
INDIANAPOLIS (Reuters) - There can only be one winner in Sunday's Super Bowl but for two opposing players, a bigger battle has already been won, victory over cancer. New York Giants linebacker Mark Herzlich and New England Patriots offensive l...
-
Some former Komen supporters can't forgive, forget
When Dorothy Twinney first saw a Race for the Cure walk for breast cancer — "a sea of pink" traveling through her hometown of Plymouth, Mich. — she was so moved she sat in her car and wept.
-
Don't Fumble Your Diet on Super Bowl Sunday
SATURDAY, Feb. 4 (HealthDay News) -- All the food and beverages served at Super Bowl parties can make it a challenging day for people who made a New Year's resolution to lose weight.
-
Winter Can Pose Hazards for Seniors
SATURDAY, Feb. 4 (HealthDay News) -- Winter weather can be challenging for some seniors, especially those with mobility or other health issues.
-
Germany wages war against 'burnout'
Germany, holding up better than its eurozone partners in the current debt crisis, is battling the increasingly widespread phenomenon of "burnout" which it says is costing its economy billions of euros (dollars) each year.
-
Breastfeeding tied to stronger lungs, less asthma
NEW YORK (Reuters Health) - Kids who were breastfed as babies may have better lung function, and a lower risk of asthma, than those who were formula-fed, two new reports suggest. Researchers said that past studies have found conflicting results wh...
-
Allergan to rely less on U.S. for sales, Asia key
(Reuters) - Allergan Inc, maker of wrinkle treatment Botox, eye drops and obesity treatments, said it will rely less on the United States for revenue in coming years as its products gain wider acceptance in Asia, particularly China. The company on...
-
Insight: In PIP implant scandal, a ragged safety net exposed
LONDON (Reuters) - In June 2000, when American medical regulators posted a warning letter on the Internet about problems at a breast-implant maker in southern France, French authorities didn't pay much attention. A U.S. Food and Drug Administr...
-
Maine girl bouncing back after 6-organ transplant
A 9-year-old Maine girl is home from a Boston hospital healthy, active and with high hopes — and a new stomach, liver, spleen, small intestine, pancreas, and part of an esophagus to replace the ones that were being choked by a huge tumor.
-
Health Tip: Prepare for Breast-feeding
(HealthDay News) -- Preparations for successful breast-feeding begin during pregnancy.
-
Health Tip: Teach Your Toddler Good Behavior
(HealthDay News) -- Toddler tantrums can challenge even the most patient parent, but being firm and consistent can help you discipline your toddler in an effective, loving way.
-
Walgreen sales hit by exit from Express Scripts
(Reuters) - Walgreen Co is being hit by its withdrawal from the Express Scripts Inc pharmacy network and by a much-weaker-than-expected flu season, leading it to temper its expectations for the number of prescriptions it will fill this year. Walgr...
-
Malaria death toll possibly twice as high
Malaria may be killing around twice as many people as experts previously thought, and it could also be hitting older children and adults — long considered the least susceptible — a new study suggests.
-
Bloomberg pledges $250,000 to Planned Parenthood
NEW YORK (Reuters) - Billionaire New York City Mayor Michael Bloomberg pledged on Thursday to give $250,000 of his own money to the Planned Parenthood Federation of America after breast cancer charity Susan G. Komen for the Cure withdrew funding f...
-
Senators urge Komen to reconsider funding decision
WASHINGTON (Reuters) - Some two dozen Democrats in the Senate on Thursday called on breast cancer charity Susan G. Komen for the Cure to reconsider its decision to cut off funding to the Planned Parenthood Federation of America. Senators Frank Lau...
-
Strong jobs report pushes Nasdaq to 11-year high
NEW YORK (Reuters) - U.S. stocks rose on Friday, propelling the Nasdaq index to an 11-year high, after January's U.S. employment report sailed past expectations, boosting hopes the world's largest economy has turned a corner. The broad-bas...
-
New map pinpoints Lyme disease risk areas
Researchers who spent three years dragging sheets of fabric through the woods to snag ticks have created a detailed map they claim could improve prevention, diagnosis and treatment of Lyme disease.
-
Nerve disorder does not recur after later vaccines: study
NEW YORK (Reuters Health) - Despite concerns by some that vaccines might cause a crippling nerve disorder called Guillain-Barré syndrome, a new study finds that people who receive vaccines after previously having been diagnosed with the condition ...
-
Jobs strength lifts Nasdaq to 11-year high
NEW YORK (Reuters) - A surge in hiring last month lifted U.S. stocks on Friday, with the Nasdaq index hitting an 11-year high, as the data boosted hopes the world's largest economy has turned a corner. The broad-based gains also sent the Dow J...
-
Breast cancer fund to restore funding after outcry
A major US breast cancer foundation Friday reversed its decision to stop funding Planned Parenthood after outcry over the move sparked a political and fundraising backlash by women's health advocates.
-
Malaria kills twice as many as thought: study
LONDON (Reuters) - Malaria kills more than 1.2 million people worldwide a year, nearly twice as many as previously thought, according to new research published on Friday that questions years of assumptions about the mosquito-borne disease. Past st...
|
|
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
|
Yahoo! Health News
|
-
Dealing With Head Lice
SUNDAY, Feb. 5 (HealthDay News) -- Although there is a stigma associated with having head lice, infestations with these small insects are common and nothing to be ashamed of, according to Dr. Hannah Chow-Johnson, a pediatrician at Loyola Universit...
-
Olympus to hold shareholder meeting on April 20
TOKYO (Reuters) - Japan's troubled Olympus Corp said on Sunday it will hold an extraordinary shareholders meeting on April 20, when it is expected to seek approval of a new management team. The maker of cameras and medical equipment is struggl...
-
Safe Social Networking Tips for Teens
SUNDAY, Feb. 5 (HealthDay News) -- More than 60 percent of American teens have at least one profile on a social networking site, and many spend more than two hours a day on social networking sites, according to the American Academy of Child and Ad...
-
Parents urge more tests as twitches spread at New York school
LE ROY, New York (Reuters) - State health officials have added three more names to a growing list of students in this working-class town who are experiencing mysterious tics and twitching, while authorities on Saturday sought to assure parents the...
-
Cancer survivors line up as opponents in Super Bowl
INDIANAPOLIS (Reuters) - There can only be one winner in Sunday's Super Bowl but for two opposing players, a bigger battle has already been won, victory over cancer. New York Giants linebacker Mark Herzlich and New England Patriots offensive l...
-
Some former Komen supporters can't forgive, forget
When Dorothy Twinney first saw a Race for the Cure walk for breast cancer — "a sea of pink" traveling through her hometown of Plymouth, Mich. — she was so moved she sat in her car and wept.
-
Don't Fumble Your Diet on Super Bowl Sunday
SATURDAY, Feb. 4 (HealthDay News) -- All the food and beverages served at Super Bowl parties can make it a challenging day for people who made a New Year's resolution to lose weight.
-
Winter Can Pose Hazards for Seniors
SATURDAY, Feb. 4 (HealthDay News) -- Winter weather can be challenging for some seniors, especially those with mobility or other health issues.
-
Germany wages war against 'burnout'
Germany, holding up better than its eurozone partners in the current debt crisis, is battling the increasingly widespread phenomenon of "burnout" which it says is costing its economy billions of euros (dollars) each year.
-
Breastfeeding tied to stronger lungs, less asthma
NEW YORK (Reuters Health) - Kids who were breastfed as babies may have better lung function, and a lower risk of asthma, than those who were formula-fed, two new reports suggest. Researchers said that past studies have found conflicting results wh...
-
Allergan to rely less on U.S. for sales, Asia key
(Reuters) - Allergan Inc, maker of wrinkle treatment Botox, eye drops and obesity treatments, said it will rely less on the United States for revenue in coming years as its products gain wider acceptance in Asia, particularly China. The company on...
-
Insight: In PIP implant scandal, a ragged safety net exposed
LONDON (Reuters) - In June 2000, when American medical regulators posted a warning letter on the Internet about problems at a breast-implant maker in southern France, French authorities didn't pay much attention. A U.S. Food and Drug Administr...
-
Maine girl bouncing back after 6-organ transplant
A 9-year-old Maine girl is home from a Boston hospital healthy, active and with high hopes — and a new stomach, liver, spleen, small intestine, pancreas, and part of an esophagus to replace the ones that were being choked by a huge tumor.
-
Health Tip: Prepare for Breast-feeding
(HealthDay News) -- Preparations for successful breast-feeding begin during pregnancy.
-
Health Tip: Teach Your Toddler Good Behavior
(HealthDay News) -- Toddler tantrums can challenge even the most patient parent, but being firm and consistent can help you discipline your toddler in an effective, loving way.
-
Walgreen sales hit by exit from Express Scripts
(Reuters) - Walgreen Co is being hit by its withdrawal from the Express Scripts Inc pharmacy network and by a much-weaker-than-expected flu season, leading it to temper its expectations for the number of prescriptions it will fill this year. Walgr...
-
Malaria death toll possibly twice as high
Malaria may be killing around twice as many people as experts previously thought, and it could also be hitting older children and adults — long considered the least susceptible — a new study suggests.
-
Bloomberg pledges $250,000 to Planned Parenthood
NEW YORK (Reuters) - Billionaire New York City Mayor Michael Bloomberg pledged on Thursday to give $250,000 of his own money to the Planned Parenthood Federation of America after breast cancer charity Susan G. Komen for the Cure withdrew funding f...
-
Senators urge Komen to reconsider funding decision
WASHINGTON (Reuters) - Some two dozen Democrats in the Senate on Thursday called on breast cancer charity Susan G. Komen for the Cure to reconsider its decision to cut off funding to the Planned Parenthood Federation of America. Senators Frank Lau...
-
Strong jobs report pushes Nasdaq to 11-year high
NEW YORK (Reuters) - U.S. stocks rose on Friday, propelling the Nasdaq index to an 11-year high, after January's U.S. employment report sailed past expectations, boosting hopes the world's largest economy has turned a corner. The broad-bas...
-
New map pinpoints Lyme disease risk areas
Researchers who spent three years dragging sheets of fabric through the woods to snag ticks have created a detailed map they claim could improve prevention, diagnosis and treatment of Lyme disease.
-
Nerve disorder does not recur after later vaccines: study
NEW YORK (Reuters Health) - Despite concerns by some that vaccines might cause a crippling nerve disorder called Guillain-Barré syndrome, a new study finds that people who receive vaccines after previously having been diagnosed with the condition ...
-
Jobs strength lifts Nasdaq to 11-year high
NEW YORK (Reuters) - A surge in hiring last month lifted U.S. stocks on Friday, with the Nasdaq index hitting an 11-year high, as the data boosted hopes the world's largest economy has turned a corner. The broad-based gains also sent the Dow J...
-
Breast cancer fund to restore funding after outcry
A major US breast cancer foundation Friday reversed its decision to stop funding Planned Parenthood after outcry over the move sparked a political and fundraising backlash by women's health advocates.
-
Malaria kills twice as many as thought: study
LONDON (Reuters) - Malaria kills more than 1.2 million people worldwide a year, nearly twice as many as previously thought, according to new research published on Friday that questions years of assumptions about the mosquito-borne disease. Past st...
|
|
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
Notice: Only variable references should be returned by reference in /var/www/vhosts/pmandr.com/httpdocs/includes/domit/xml_domit_nodemaps.php on line 166
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Fluids and Barriers of the CNS - Latest Articles
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Temporal course of cerebrospinal fluid dynamics and amyloid accumulation in the aging rat brain from three to thirty months
Background:
Amyloid accumulation in the brain parenchyma is a hallmark of Alzheimer's disease (AD) and is seen in normal aging. Alterations in cerebrospinal fluid (CSF) dynamics are also associated with normal aging and AD. This study analyzed CSF volume, production and turnover rate in relation to amyloid-beta peptide (Abeta) accumulation in the aging rat brain. Methods: Aging Fischer 344/Brown-Norway hybrid rats at 3, 12, 20, and 30 months were studied. CSF production was measured by ventriculo-cisternal perfusion with blue dextran in artificial CSF; CSF volume by MRI; and CSF turnover rate by dividing the CSF production rate by the volume of the CSF space. Abeta40 and Abeta42 concentrations in the cortex and hippocampus were measured by ELISA. Results: There was a significant linear increase in total cranial CSF volume with age: 3-20 months (p<0.01); 3-30 months (p<0.001). CSF production rate increased from 3-12 months (p<0.01) and decreased from 12-30 months (p<0.05). CSF turnover showed an initial increase from 3 months (9.40 day-1) to 12 months (11.30 day-1) and then a decrease to 20 months (10.23 day-1) and 30 months (6.62 day-1). Abeta40 and Abeta42 concentrations in brain increased from 3-30 months (p<0.001). Both Abeta42 and Abeta40 concentrations approached a steady state level by 30 months. Conclusions: In young rats there is no correlation between CSF turnover and Abeta brain concentrations. After 12 months, CSF turnover decreases as brain Abeta continues to accumulate. This decrease in CSF turnover rate may be one of several clearance pathway alterations that influence age-related accumulation of brain amyloid.
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Intrastriatal convection-enhanced delivery results in widespread perivascular distribution in a pre-clinical model
Background:
Convection-enhanced delivery (CED), a direct method for drug delivery to the brain through intraparenchymal microcatheters, is a promising strategy for intracerebral pharmacological therapy. By establishing a pressure gradient at the tip of the catheter, drugs can be delivered in uniform concentration throughout a large volume of interstitial fluid. However, the variables affecting perivascular distribution of drugs delivered by CED are not fully understood. The aim of this study was to determine whether the perivascular distribution of solutes delivered by CED into the striatum of rats is affected by the molecular weight of the infused agent, by co-infusion of vasodilator, alteration of infusion rates or use of a ramping regime. We also wanted to make a preliminary comparison of the distribution of solutes with that of nanoparticles.
Methods:
We analysed the perivascular distribution of 4, 10, 20, 70, 150kDa fluorescein-labelled dextran and fluorescent nanoparticles at 10 min and 3h following CED into rat striatum. We investigated the effect of local vasodilatation, slow infusion rates and ramping on the perivascular distribution of solutes. Co-localisation with perivascular basement membranes and vascular endothelial cells was identified by immunohistochemistry. The uptake of infusates by perivascular macrophages was quantified using stereological methods.
Results:
Widespread perivascular distribution and macrophage uptake of fluorescein-labelled dextran was visible 10 min after cessation of CED irrespective of molecular weight. However, a significantly higher proportion of perivascular macrophages had taken up 4, 10 and 20kDa fluorescein-labelled dextran than 150kDa dextran (p <0.05, ANOVA). Co-infusion with vasodilator, slow infusion rates and use of a ramping regime did not alter the perivascular distribution. CED of fluorescent nanoparticles indicated that particles co-localise with perivascular basement membranes throughout the striatum but, unlike soluble dextrans, are not taken up by perivascular macrophages after 3h.
Conclusions:
This study suggests that widespread perivascular distribution and interaction with perivascular macrophages is likely to be an inevitable consequence of CED of solutes. The potential consequences of perivascular distribution of therapeutic agents, and in particular cytotoxic chemotherapies, delivered by CED must be carefully considered to ensure safe and effective translation to clinical trials.
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The value of cerebrospinal fluid tap test for predicting shunt effectiveness in idiopathic normal pressure hydrocephalus
Background The cerebrospinal fluid (CSF) tap test (TT) has been regarded as an important test for the prediction of shunt effectiveness in patients with suspected idiopathic normal pressure hydrocephalus (iNPH). Although its specificity and sensitivity are reportedly high, there remains some disagreement over this point. Herein, the TT as a test for predicting shunt effectiveness was investigated in our multicenter prospective study named SINPHONI and strategies to increase its predictability were examined.Methods One hundred suspected iNPH patients with the following entry criteria were enrolled in the study: (1) 60 to 85 years old, (2) one or more of the NPH triad signs, (3) ventriculomegaly (Evans index > 0.3), (4) high convexity tightness in coronal-section MRI, and (5) no antecedent disorders. Changes in NPH triad symptoms were assessed using the iNPH grading scale and other measures before and after removal of 30ml lumbar CSF. A positive response to TT was pre-defined by specific improvements on the grading and other scales. A ventriculoperitoneal shunt was performed with a programmable valve. The sensitivity and specificity of the TT was calculated with a contingency table. A decision tree analysis was performed to increase the predictability of the TT.Results Among 100 patients, 80 were shunt responders. A statistically-significant variable between shunt responders and non-responders was CSF pressure. The changes in single variables in the iNPH grading scale after TT showed high specificity with low sensitivity. In contrast, change of the total score in the iNPH grading scale showed a relatively high sensitivity of 71.3% with specificity of 65%. A decision tree analysis revealed that using the iNPH grading scale total score and pre-shunt CSF pressure [greater than or equal to]15 cmH20, sensitivity increased to 82.5%, without a decrease in specificity.Conclusions The sensitivity and specificity of the TT for predicting shunt responsiveness were optimum when improvement on any iNPH grading scale was combined with CSF pressure [greater than or equal to]15 cmH20. To increase the sensitivity of the TT, further effort is necessary. This study is registered with ClinicalTrials.gov, with the number NCT00221091.
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Choroid plexus transport: gene deletion studies
This review examines the use of transporter knockout (KO) animals to evaluate transporter function at the choroid plexus (the blood-CSF barrier; BCSFB). Compared to the blood-brain barrier, there have been few such studies on choroid plexus (CP) function. These have primarily focused on Pept2 (an oligopeptide transporter), ATP-binding cassette (ABC) transporters, Oat3 (an organic anion transporter), Svct2 (an ascorbic acid transporter), transthyretin, ion transporters, and ion and water channels. This review focuses on the knowledge gained from such studies, both with respect to specific transporters and in general to the role of the CP and its impact on brain parenchyma. It also discusses the pros and cons of using KO animals in such studies and the technical approaches that can be used.
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Fibrinogen is not elevated in the cerebrospinal fluid of patients with multiple sclerosis
Background:
Elevated plasma fibrinogen levels are a well known finding in acute infectious diseases, acute stroke and myocardial infarction. However its role in the cerebrospinal fluid (CSF) of acute and chronic central (CNS) and peripheral nervous system (PNS) diseases is unclear.FindingsWe analyzed CSF and plasma fibrinogen levels together with routine parameters in patients with multiple sclerosis (MS), acute inflammatory diseases of the CNS (bacterial and viral meningoencephalitis, BM and VM) and PNS (Guillain-Barré syndrome; GBS), as well as in non-inflammatory neurological controls (OND) in a total of 103 patients. Additionally, MS patients underwent cerebral MRI scans at time of lumbar puncture.CSF and plasma fibrinogen levels were significantly lower in patients with MS and OND patients as compared to patients with BM, VM and GBS. There was a close correlation between fibrinogen levels and albumin quotient (rho = 0.769, p < 0.001) which strongly suggests passive transfer of fibrinogen through the blood-CSF-barrier during acute inflammation. Hence, in MS, the prototype of chronic neuroinflammation, CSF fibrinogen levels were not elevated and could not be correlated to clinical and neuroradiological outcome parameters.
Conclusions:
Although previous work has shown clear evidence of the involvement of fibrinogen in MS pathogenesis, this is not accompanied by increased fibrinogen in the CSF compartment.
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Attenuation of prostaglandin E2 elimination across the mouse blood-brain barrier in lipopolysaccharide-induced inflammation and additive inhibitory effect of cefmetazole
Background:
Peripheral administration of lipopolysaccharide (LPS) induces inflammation and increases cerebral prostaglandin E2 (PGE2) concentration. PGE2 is eliminated from brain across the blood-brain barrier (BBB) in mice, and this process is inhibited by intracerebral or intravenous pre-administration of anti-inflammatory drugs and antibiotics such as cefmetazole and cefazolin that inhibit multidrug resistance-associated protein 4 (Mrp4/Abcc4)-mediated PGE2 transport. The purpose of this study was to examine the effect of LPS-induced inflammation on PGE2 elimination from brain, and whether antibiotics further inhibit PGE2 elimination in LPS-treated mice.
Methods:
[3H]PGE2 elimination across the BBB of intraperitoneally LPS-treated mice was assessed by the brain efflux index (BEI) method. Transporter protein amounts in brain capillaries were quantified by liquid chromatography-tandem mass spectrometry.
Results:
The apparent elimination rate of [3H]PGE2 from brain was lower by 87%, in LPS-treated mice compared with saline-treated mice. The Mrp4 protein amount was unchanged in brain capillaries of LPS-treated mice compared with saline-treated mice, while the protein amounts of organic anion transporter 3 (Oat3/Slc22a8) and organic anion transporting polypeptide 1a4 (Oatp1a4/Slco1a4) were decreased by 26% and 39%, respectively. Either intracerebral or intravenous pre-administration of cefmetazole further inhibited PGE2 elimination in LPS-treated mice. However, intracerebral or intravenous pre-administration of cefazolin had little effect on PGE2 elimination in LPS-treated mice, or in LPS-untreated mice given Oat3 and Oatp1a4 inhibitors. These results indicate that peripheral administration of cefmetazole inhibits PGE2 elimination across the BBB in LPS-treated mice.
Conclusion:
PGE2 elimination across the BBB is attenuated in an LPS-induced mouse model of inflammation. Peripheral administration of cefmetazole further inhibits PGE2 elimination in LPS-treated mice.
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Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and diesel exhaust particles in rat brain microvessels
Background:
AhR activates the transcription of several target genes including CYP1B1. Recently, we showed CYP1B1 as the major cytochrome P450 (CYP) enzyme expressed in human brain microvessels. Here, we studied the effect of AhR activation by environmental pollutants on the expression of Cyp1b1 in rat brain microvessels.
Methods:
Expression of AhR and Cyp1b1 was detected in isolated rat brain microvessels. AhR was immunovisualised in brain microvessel endothelial cells. The effect of AhR ligands on Cyp1b1 expression was studied using isolated brain microvessels after ex vivo and/or in vivo exposure to TCDD, heavy hydrocarbons containing diesel exhaust particles (DEP) or Δ9-tetrahydrocannabinol (Δ9-THC).
Results:
After ex vivo exposure to TCDD (a highly potent AhR ligand) for 3 h, Cyp1b1 expression was significantly increased by 2.3-fold in brain microvessels. A single i.p. dose of TCDD also increased Cyp1b1 transcripts (22-fold) and Cyp1b1 protein (2-fold) in rat brain microvessels at 72 h after TCDD. Likewise, DEP treatment (in vivo and ex vivo) strongly induced Cyp1b1 protein in brain microvessels. DEP-mediated Cyp1b1 induction was inhibited by actinomycin D, cycloheximide, or by an AhR antagonist. In contrast, a sub-chronic in vivo treatment with Δ9-THC once daily for 7 seven days had no effect on Cyp1b1 expression
Conclusions:
Our results show that TCDD and DEP strongly induced Cyp1b1 in rat brain microvessels, likely through AhR activation.
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Magnetic resonance imaging indicators of blood-brain barrier and brain water changes in young rats with kaolin-induced hydrocephalus.
Background:
Hydrocephalus is associated with enlargement of cerebral ventricles. We hypothesized that magnetic resonance (MR) imaging parameters known to be influenced by tissue water content would change in parallel with ventricle size in young rats and that changes in blood-brain barrier (BBB) permeability would be detected.
Methods:
Hydrocephalus was induced by injection of kaolin into the cisterna magna of 4-week-old rats, which were studied 1 or 3 weeks later. MR was used to measure longitudinal and transverse relaxation times (T1 and T2) and apparent diffusion coefficients in several regions. Brain tissue water content was measured by the wet-dry weight method, and tissue density was measured in Percoll gradient columns. BBB permeability was measured by quantitative imaging of changes on T1-weighted images following injection of gadolinium diethylenetriamine penta-acetate (Gd-DTPA) tracer and microscopically by detection of fluorescent dextran conjugates.
Results:
In nonhydrocephalic rats, water content decreased progressively from age 3 to 7 weeks. T1 and T2 and apparent diffusion coefficients did not exhibit parallel changes and there was no evidence of BBB permeability to tracers. The cerebral ventricles enlarged progressively in the weeks following kaolin injection. In hydrocephalic rats, the dorsal cortex was more dense and the white matter less so, indicating that the increased water content was largely confined to white matter. Hydrocephalus was associated with transient elevation of T1 in gray and white matter and persistent elevation of T2 in white matter. Changes in the apparent diffusion coefficients were significant only in white matter. Ventricle size correlated significantly with dorsal water content, T1, T2, and apparent diffusion coefficients. MR imaging showed evidence of Gd-DTPA leakage in periventricular tissue foci but not diffusely. These correlated with microscopic leak of larger dextran tracers.
Conclusions:
MR characteristics cannot be used as direct surrogates for water content in the immature rat model of hydrocephalus, probably because they are also influenced by other changes in tissue composition that occur during brain maturation. There is no evidence for widespread persistent opening of BBB as a consequence of hydrocephalus in young rats. However, increase in focal BBB permeability suggests that periventricular blood vessels may be disrupted.
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Amyloid-beta transporter expression at the blood-CSF barrier is age-dependent
Background:
Age is the major risk factor for many neurodegenerative diseases, including Alzheimer's disease (AD). There is an accumulation of amyloid-beta peptides (Aβ) in both the AD brain and the normal aging brain. Clearance of Aβ from the brain occurs via active transport at the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). With increasing age, the expression of the Aβ efflux transporters is decreased and the Aβ influx transporter expression is increased at the BBB, adding to the amyloid burden in the brain. Expression of the Aβ transporters at the choroid plexus (CP) epithelium as a function of aging was the subject of this study.
Methods:
This project investigated the changes in expression of the Aβ transporters, the low density lipoprotein receptor-related protein-1 (LRP-1), P-glycoprotein (P-gp), LRP-2 (megalin) and the receptor for advanced glycation end-products (RAGE) at the BCSFB in Brown-Norway/Fischer rats at ages 3, 6, 9, 12, 20, 30 and 36 months, using real time RT-PCR to measure transporter mRNA expression, and immunohistochemistry (IHC) to measure transporter protein in isolated rat CP.
Results:
There was an increase in the transcription of the Aβ efflux transporters, LRP-1 and P-gp, no change in RAGE expression and a decrease in LRP-2, the CP epithelium influx transporter, at the BCSFB with aging. Decreased Aβ42 concentration in the CP, as measured by quantitative IHC, was associated with these Aβ transporter alterations.
Conclusions:
Age-dependent alterations in the CP Aβ transporters are associated with a decrease in Aβ42 accumulation in the CP, and are reciprocal to the changes seen in these transporters at the BBB, suggesting a possible compensatory role for the BCSFB in Aβ clearance in aging.
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1α,25-Dihydroxyvitamin D3 enhances cerebral clearance of human amyloid-β peptide(1-40) from mouse brain across the blood-brain barrier
Background:
Cerebrovascular dysfunction has been considered to cause impairment of cerebral amyloid-β peptide (Aβ) clearance across the blood-brain barrier (BBB). Further, low levels of vitamin D are associated with increased risk of Alzheimer's disease, as well as vascular dysfunction. The purpose of the present study was to investigate the effect of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), an active form of vitamin D, on cerebral Aβ clearance from mouse brain.
Methods:
The elimination of [125I]hAβ(1-40) from mouse brain was examined by using the Brain Efflux Index method to determine the remaining amount of [125I]hAβ(1-40) radioactivity after injection into the cerebral cortex. [125I]hAβ(1-40) internalization was analyzed using conditionally immortalized mouse brain capillary endothelial cells (TM-BBB4).
Results:
Twenty-four hours after intraperitoneal injection of 1,25(OH)2D3 (1 μg/mouse), [125I]hAβ(1-40) elimination from mouse brain was increased 1.3-fold, and the level of endogenous Aβ(1-40) in mouse brain was reduced. These effects were observed at 24 h after i.p. injection of 1,25(OH)2D3, while no significant effect was observed at 48 or 72 h. Vitamin D receptor (VDR) mRNA was detected in mouse brain capillaries, suggesting that 1,25(OH)2D3 has a VDR-mediated genomic action. Furthermore, forskolin, which activates mitogen-activated protein kinase kinase (MEK), enhanced [125I]hAβ(1-40) elimination from mouse brain. Forskolin also enhanced [125I]hAβ(1-40) internalization in TM-BBB4 cells, and this enhancement was inhibited by a MEK inhibitor, suggesting involvement of non-genomic action.
Conclusions:
The active form of vitamin D, 1,25(OH)2D3, appears to enhance brain-to-blood Aβ(1-40) efflux transport at the BBB through both genomic and non-genomic actions. Compounds activating these pathways may be candidate agents for modulating Aβ(1-40) elimination at the BBB.
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Cough - Latest Articles
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An observational study on cough in children: epidemiology, impact on quality of sleep and treatment outcome
Background:
Cough is one of the most frequent symptoms in children and is the most common symptom for which children visit a health care provider.
Methods:
This is an observational study on acute cough associated with upper respiratory tract infection (URTI) in children. The study evaluates the epidemiology and impact of cough on quality of sleep and children's activities, and the outcome of cough with antitussive treatments in pediatric routine clinical practice. Study assessments were performed through a pediatric cough questionnaire (PCQ), developed by the Italian Society of Cough Study. A total of 433 children visited by family care pediatricians for acute cough due to an URTI were enrolled in this study, with mean age of 6.1 years (SD 3.6). Cough type, duration, severity and frequency, cough impact on sleep disturbances of children and parents and on school and sport activities were assessed at baseline. In a subset of 241 children who were either treated with antitussive drugs (levodropropizine n=101, central antitussives n=60) or received no treatment (n=80), the outcome of cough after 6 days was analyzed in terms of resolution, improvement, no change, or worsening. Descriptive analysis, chi sq, and multivariate analysis with stepwise logistic regression were performed.
Results:
Cough disturbed sleep in 88% of children and 72% of parents. In children treated with cough suppressants, the duration, type, intensity, and frequency cough were similar at baseline in the two groups respectively treated with levodropropizine and central antitussives (cloperastine and codeine). Both levodropropizine and central drugs reduced cough intensity and frequency. However, percentage of cough resolution was higher with levodropropizine than with central antitussives (47% vs. 28% respectively, p=0.0012).
Conclusions:
Acute cough disturbs sleep in most children and their parents. Both levodropropizine and central antitussives reduced cough intensity, with levodropropizine producing a higher cough resolution rate.
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The objective assessment of cough frequency: accuracy of the LR102 device.
Background:
The measurement of cough frequency is problematic and most often based on subjective assessment. The aim of the study was to assess the accuracy of the automatic identification of cough episodes by LR102, a cough frequency meter based on electromyography and audio sensors.
Methods:
Ten adult patients complaining of cough were recruited in primary care and hospital settings. Participants were asked to wear LR102 for 4 consecutive hours during which they were also filmed.
Results:
Measures of cough frequency by LR102 and manual counting were closely correlated (r = 0.87 for number of cough episodes per hour; r = 0.89 for number of single coughs per hour) but LR102 overestimated cough frequency. Bland-Altman plots indicate that differences between the two measurements were not influenced by cough frequency.
Conclusions:
LR102 offers a useful estimate of cough frequency in adults in their own environment, while significantly reducing the time required for analysis.
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Perspective on the human cough reflex
This review dissects the complex human cough reflex and suggests hypotheses about the evolutionary basis for the reflex. A mechanosensory-induced cough reflex conveys through branches of myelinated Aδ nerve fibers is not chemically reactive (i.e., capsaicin, bradykinin); possibly, its evolution is to prevent the harmful effects of aspiration of gastric or particulate contents into the lungs. This became necessary as the larynx moves closer to the opening of the esophagus as human ancestors adapt phonation over olfaction beginning less than 10 million years ago. The second type of cough reflex, a chemosensory type, is carried by unmyelinated C fibers. Supposedly, its origin dates back when prehistoric humans began living in close proximity to each other and were at risk for infectious respiratory diseases or irritant-induced lung injury. The mechanism for the latter type of cough is analogous to induced pain after tissue injury; and, it is controlled by the identical transient receptor potential vanilloid cation channel (TRPV1). The airways do not normally manifest nociceptive pain from a stimulus but the only consistent response that capsaicin and lung inflammation provoke in healthy human airways is cough. TRPA1, another excitatory ion channel, has been referred to as the "irritant receptor" and its activation also induces cough. For both types of cough, the motor responses are identical and via coordinated, precisely-timed and sequential respiratory events orchestrated by complex neuromuscular networking of the diaphragm, chest and abdominal respiratory muscles, the glottis and parts of the brain.
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Posture influences patient cough rate, sedative requirement and comfort during bronchoscopy: An observational cohort study.
ObjectivesTo investigate differences between semi-recumbent and supine postures in terms of cough rate, oxygen desaturation, sedative use, and patient comfort during the initial phase of bronchoscopy.
Methods:
Consecutive bronchoscopy patients (n = 69) participated in this observational cohort study. Posture was determined by the bronchoscopist's usual practice. Patient demographics, spirometry, pulse, and SpO2 were recorded. The initial phase was defined as the time from bronchoscopy insertion to visualisation of both distal main bronchi. Cough rate, peak pulse, nadir SpO2, oxygen supplementation, and sedative use during the initial phase were recorded. A post-procedure questionnaire was administered to the patient and the attending nurse.
Results:
36 patients had bronchoscopy in the semi-recumbent posture, 33 in the supine posture. 3 of 5 bronchoscopists performed in both postures. There were no differences in baseline parameters between the groups. The semi-recumbent posture resulted in significantly less cough (mean (SD) 3.6 (2.3) vs. 6.1 (4.5) coughs/min, p = 0.007) and less fentanyl use (70 (29) vs. 88 (28) mcg, p = 0.011) in the initial phase. There were no significant differences in the nadir SpO2, fall in SpO2, oxygen supplementation, or increase in pulse rate between the groups. On 100 mm visual analogue scale, nurse perception of patient discomfort was lower in the semi-recumbent position (23 (21) vs. 39 (28) mm, p = 0.01), and there was a trend towards less patient perceived cough in the semi-recumbent group (28 (25) vs. 40 (28) mm, p = 0.06).
Conclusions:
Bronchoscopy performed in the semi-recumbent posture results in less cough and sedative requirement, and may improve patient comfort.
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Cough response to isocapnic hyperpnoea of dry air and hypertonic saline are interrelated
Background:
Mechanisms behind asthmatic cough are largely unknown. It is known that hyperosmolar challenges provoke cough in asthmatic but not in the healthy subjects. It has been postulated that isocapnic hyperpnea of dry air (IHDA) and hypertonic aerosols act via similar mechanisms in asthma to cause bronchoconstriction. We investigated whether there is an association between cough response induced by IHDA and hypertonic saline (HS) challenges.
Methods:
Thirty-six asthmatic and 14 healthy subjects inhaled HS solutions with increasing osmolalities administered via ultrasonic nebuliser until 15 cumulative coughs were recorded. The IHDA consisted of three three-minute ventilation steps: 30%, 60% and 100% of maximal voluntary ventilation with an end-point of 30 cumulative coughs. The challenges were performed on separate days at least 48 hours between them and within one week. Inhaled salbutamol (400 mcg) was administered before the challenges to prevent bronchoconstriction. The cough response was expressed as the cough-to-dose ratio (CDR) which is the total number of coughs divided by the maximal osmolality inhaled or the maximal ventilation achieved.
Results:
Cough response to IHDA correlated with the HS challenge (Rs = 0.59, p < 0.001). Cough response to IHDA was at its strongest during the first minute after the challenge. IHDA induced more cough among asthmatic than healthy subjects CDR being (mean ± SD) 0.464 ± 0.514 and 0.011 ± 0.024 coughs/MVV%, p < 0.001, respectively. Salbutamol effectively prevented bronchoconstriction to both challenges.
Conclusions:
Asthmatic patients are hypersensitive to the cough-provoking effect of hyperpnoea, as they are to hypertonicity. Cough response induced by IHDA and HS correlated well suggesting similar mechanisms behind the responses.
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Cough management: a practical approach
Cough is one of the most common symptoms for which patients seek medical attention from primary care physicians and pulmonologists. Cough is an important defensive reflex that enhances the clearance of secretions and particles from the airways and protects the lower airways from the aspiration of foreign materials. Therapeutic suppression of cough may be either disease-specific or symptom related. The potential benefits of an early treatment of cough could include the prevention of the vicious cycle of cough. There has been a long tradition in acute cough, which is frequently due to upper respiratory tract infections, to use symptom-related anti-tussives. Suppression of cough (during chronic cough) may be achieved by disease-specific therapies, but in many patients it is often necessary to use symptomatic anti-tussives, too. According to the current guidelines of the American College of Chest Physician on "Cough Suppressants and Pharmacologic Protussive Therapy" and additional clinical trials on the most frequent anti-tussive drugs, it should be possible to diagnose and treat cough successfully in a majority of cases. Among drugs used for the symptomatic treatment of cough, peripherally acting anti-tussives such as levodropropizine and moguisteine show the highest level of benefit and should be recommended especially in children. By improving our understanding of the specific effects of these anti-tussive agents, the therapeutic use of these drugs may be refined. The present review provides a summary of the most clinically relevant anti-tussive drugs in addition to their potential mechanism of action.
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Symptoms induced by environmental irritants and health-related quality of life in patients with chronic cough - a cross-sectional study
Background:
Chronic cough is a common condition, but some patients have no evident medical explanation for their symptoms. A group of patients has been identified, characterized by upper and lower airway symptoms triggered by chemicals and scents, and heightened cough sensitivity to inhaled capsaicin. Chronic cough is usually a prominent symptom in these patients, and it has been suggested that they suffer from sensory hyperreactivity.Our main aim was to analyse, in a group of patients with chronic cough, the presence of symptoms induced by environmental factors such as chemicals, scents, and cold air, and to measure the social and emotional influences of these symptoms in relation to quality of life. A second aim was to pilot-test a Swedish translation of a cough-specific questionnaire.
Methods:
A total of 119 patients with chronic cough were asked to answer three different questionnaires: a local symptom questionnaire, the Chemical Sensitivity Scale for Sensory Hyperreactivity (CSS-SHR), and the Nottingham Health Profile (NHP). In addition, a Swedish version of the Hull Airway Reflux Questionnaire (HARQ) was developed and answered by a subgroup of patients and healthy controls.
Results:
Sixty-two patients (52%) with mean cough duration of 10.6 years answered the local symptom questionnaire, the CSS-SHR, and the NHP. Of these, 39 (63%) claimed to have cough and other symptoms induced by chemicals and scents. Compared to population-based findings, the patients scored higher on the CSS-SHR, and the CSS-SHR score was significantly higher among chemical-sensitive individuals (p < 0.001). The NHP showed that the patients had a significantly reduced quality of life, which was most pronounced among chemical-sensitive individuals. The 31 patients who answered the HARQ had significantly higher scores (p < 0.0001) than 59 healthy controls.
Conclusions:
Among patients with chronic cough, a majority claimed that environmental factors induced coughing. Both the CSS-SHR and the HARQ score systems seem to be valuable instruments in the mapping of cough patients, supporting the novel paradigm of a cough hypersensitivity syndrome. Our results emphasize that cough is a substantial burden to the patient, influencing daily living and quality of life.
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Involvement of nitric oxide (NO) in cough reflex sensitivity between non-sensitized and OVA-sensitized guinea pigs
Background:
Exhaled nitric oxide (ENO) is elevated in bronchial asthma patients, and inhaled corticosteroid therapy lowers the elevated ENO levels in such patients. ENO appears to be an inflammatory marker, but its role in the pathophysiology of cough remains unclear. This study aimed to elucidate the relationship between NO and increased cough reflex sensitivity induced by allergic airway reactions.
Methods:
Cough reflex sensitivity to inhaled capsaicin was observed under NO depletion caused by NO synthase (NOS) inhibitors in non-sensitized and ovalbumin (OVA)-sensitized guinea pigs. The bronchoalveolar lavage fluid (BALF) was analyzed in an NO depletion setting using the inducible NOS (iNOS) inhibitor ONO1714 in OVA-sensitized guinea pigs.
Results:
NO depletion by the non-selective NOS inhibitor L-NAME suppressed cough reflex sensitivity in non-sensitized guinea pigs and OVA-induced increase in cough reflex sensitivity in sensitized guinea pigs; however, iNOS inhibition caused by ONO1714 partially suppressed the OVA-induced increase in cough reflex sensitivity, but not the normal cough response in non-sensitized guinea pigs. ONO1714 did not change BAL cell components in OVA-sensitized guinea pigs.
Conclusions:
The results suggest that NO may be involved not only in the normal cough reflex circuit, but also in the OVA-induced increase in cough reflex sensitivity, possibly via a different mechanism of action. Further studies are needed to clarify the precise mechanism.
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The assessment of quality of life in acute cough with the Leicester Cough Questionnaire (LCQ-acute)
IntroductionAcute cough has a significant impact on physical and psychosocial health and is associated with an impaired quality of life (QOL). The Leicester Cough Questionnaire (LCQ) is a validated cough-related health status questionnaire designed for patients with chronic cough. The purpose of this study was to validate the LCQ for the assessment of health related QOL in patients with acute cough and determine the clinical minimal important difference (MID).
Methods:
10 subjects with cough due to acute upper respiratory tract infection underwent focused interviews to investigate the face validity of the LCQ. The LCQ was also evaluated by a multidisciplinary team. 30 subjects completed the revised LCQ-acute and a cough visual analogue score (VAS: 0-100 mm) within one week of onset of cough and again <2 weeks later and at resolution of cough. The concurrent validity, internal reliability, repeatability and responsiveness of the LCQ-acute were also assessed. Patients also completed a Global Rating of Change Questionnaire that assessed the change in cough severity between visits. The MID was calculated as the change in LCQ-acute score for patients responding to GRCQ category representing the smallest change in health status that patients found worthwhile.
Results:
Health status was severely impaired at baseline affecting all domains; median (interquartile range) total LCQ-acute score 13.0 (3.4). All subjects found the LCQ-acute questionnaire acceptable for assessing their cough. Internal reliability of the LCQ-acute was good for all domains and total score, Cronbach's α coefficients >0.9. There was a significant correlation between LCQ-acute and VAS (ρ = -0.48, p = 0.007). The LCQ-acute and its domains were highly responsive to change; effect sizes 1.7-2.3. The MID for total LCQ and VAS were 2.5 and 13 mm respectively.
Conclusion:
The LCQ-acute is a brief, simple and valid instrument to assess cough specific health related QOL in patients with acute cough. It is a highly responsive tool suggesting that it will be particularly useful to assess the effect of antitussive therapy.
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Aging deteriorated perception of urge-to-cough without changing cough reflex threshold to citric acid in female never-smokers
Background:
The effect of aging on the cognitive aspect of cough has not been studied yet. The purpose of this study is to investigate the aging effect on the perception of urge-to-cough in healthy individuals.
Methods:
Fourteen young, female, healthy never-smokers were recruited via public postings. Twelve elderly female healthy never-smokers were recruited from a nursing home residence. The cough reflex threshold and the urge-to-cough were evaluated by inhalation of citric acid. The cough reflex sensitivities were defined as the lowest concentration of citric acid that elicited two or more coughs (C2) and five or more coughs (C5). The urge-to-cough was evaluated using a modified the Borg scale.
Results:
There was no significant difference in the cough reflex threshold to citric acid between young and elderly subjects. The urge-to-cough scores at the concentration of C2 and C5 were significantly smaller in the elderly than young subjects. The urge-to-cough log-log slope in elderly subjects (0.73 ± 0.71 point · L/g) was significantly gentler than those of young subjects (1.35 ± 0.53 point · L/g, p < 0.01). There were no significant differences in the urge-to-cough threshold estimated between young and elderly subjects.
Conclusions:
The cough reflex threshold did not differ between young and elderly subjects whereas cognition of urge-to-cough was significantly decreased in elderly subjects in female never-smokers. Objective monitoring of cough might be important in the elderly people.
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Critical Care - Latest Articles
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Clinical experience with power injectable peripherally inserted central catheters in intensive care patients
IntroductionIn intensive care units (ICU), peripherally inserted central catheters (PICC) may be an alternative option to standard central venous catheters, particularly in patients with coagulation disorders or at high risk for infection. Some limits of PICCs (such as low flow rates) may be overcome by the use of power-injectable catheters.MethodWe have retrospectively reviewed all the power injectable PICCs inserted in adult and pediatric patients in the ICU during a 12-month period, focusing on the rate of complications at insertion and during maintenance.
Results:
We have collected 89 power injectable PICCs (in adults and in children), both multiple and single lumen. All insertions were successful. There were no major complications at insertion and no episodes of catheter-related blood stream infection. Non-infective complications during management were not clinically significant. There was one episode of symptomatic thrombosis during the stay in ICU and one episode after transfer of the patient in a non-intensive ward.
Conclusions:
Power injectable PICCs have many advantages in the ICU: they can be used as multi-purpose central lines for any type of infusion including high flow infusion, for hemodynamic monitoring, and for high-pressure injection of contrast media during radiological procedures. Their insertion is successful in 100% of cases and is not associated with significant risks, even in patients with coagulation disorders. Their maintenance is associated with an extremely low rate of infective and non-infective complications.
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A prospective randomized open-label crossover trial of regional citrate anticoagulation vs. anticoagulation free
liver dialysis by the Molecular Adsorbents Recirculating System
IntroductionThe Molecular Adsorbent Recycling System (MARS) is used to treat patients with liver failure. Observational data suggest that citrate anticoagulation during MARS is feasible. Comparative studies on the optimal anticoagulation regimen during MARS are lacking. The aim of the current study was to evaluate two heparin-free anticoagulation regimens.
Methods:
We performed a prospective randomized open-label crossover study of regional citrate anticoagulation against no anticoagulation. Ten patients (age 55 +/- 11 years) with liver failure undergoing MARS treatment were included. The primary endpoint was completion of MARS sessions. Secondary endpoints included treatment efficacy and safety. Longevity of MARS treatment was plotted as a Kaplan-Meier estimate. Fisher's exact test was used for contingency table analysis.
Results:
Of a total of 27 6-hour sessions, four sessions had to be terminated prematurely, three due to occlusive clotting of the extracorporeal circuit and one due to uncontrollable bleeding from the vascular access site. All four events occurred in the group without anticoagulation. Between group comparison demonstrated citrate anticoagulation to significantly increase the likelihood of completed MARS treatment (Fisher's exact test, P 0.04). This translates into higher bilirubin reduction ratios when citrate was applied (reduction ratio 0.25 vs. 0.15, P 0.02). Systemic ionized calcium concentrations were significantly reduced during citrate anticoagulation (P<0.001) but remained within a safe range. We observed no major adverse events.
Conclusions:
Regional citrate anticoagulation in patients with liver failure is feasible. Citrate anticoagulation provides superior patency of the extracorporeal circuit. Avoidance of anticoagulation during MARS results in significant loss of treatment efficacy, due to treatment downtime. Additional studies are required to identify the optimal anticoagulation regimen for extracorporeal circulation in patients with liver failure.
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Age of blood and recipient factors determine the severity of transfusion-related acute lung injury (TRALI)
IntroductionCritical care patients frequently receive blood transfusions. Some reports show an association between aged or stored blood and increased morbidity and mortality, including the development of transfusion-related acute lung injury (TRALI). However, the existence of conflicting data endorses the need for research to either reject this association, or to confirm it and elucidate the underlying mechanisms.
Methods:
Twenty-eight sheep were randomised into two groups-- receiving saline or lipopolysaccharide (LPS). Sheep were further randomised to also receive transfusion of pooled and heat-inactivated supernatant from fresh (day 1) or stored (day 42) non-leucoreduced human packed red blood cells (PRBC) or infusion of saline. TRALI was defined by hypoxaemia during or within 2 hours of transfusion and histological evidence of pulmonary oedema. Regression modelling compared physiology between groups, and to a previous study using stored platelet concentrates (PLT). Samples of the transfused blood products also underwent cytokine array and biochemical analyses, and their neutrophil priming ability was measured in vitro.
Results:
TRALI did not develop in sheep that first received saline-infusion. In contrast, 80% of sheep that first received LPS-infusion developed TRALI following transfusion with "stored PRBC." The decreased mean arterial pressure and cardiac output as well as increased central venous pressure and body temperature were more severe for TRALI induced by "stored PRBC" than by "stored PLT." Storage-related accumulation of several factors was demonstrated in both "stored PRBC" and "stored PLT", and was associated with increased in vitro neutrophil priming. Concentrations of several factors were higher in the "stored PRBC" than in the "stored PLT," however there was no difference to neutrophil priming in vitro.
Conclusions:
In this in vivo ovine model, both recipient and blood product factors contributed to the development of TRALI. Sick (LPS infused) sheep rather than healthy (saline infused) sheep predominantly developed TRALI when transfused with supernatant from stored but not fresh PRBC. "Stored PRBC" induced a more severe injury than "stored PLT" and had a different storage lesion profile, suggesting that these outcomes may be associated with storage lesion factors unique to each blood product type. Therefore, the transfusion of fresh rather than stored PRBC may minimise the risk of TRALI.
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Pragmatic fluid optimization in high risk surgery patients: when pragmatism dilutes the benefits
There is increasing evidence that hemodynamic optimization by fluid loading, particularly when performed in the early phase of surgery, is beneficial in high-risk surgery patients: it leads to a reduction in postoperative complications and even to improved long-term outcome. However, it is also true that goal- directed strategies of fluid optimization focusing on cardiac output optimization have not been applied in the clinical routine of many institutions. Reasons are manifold: disbelief in the level of evidence and on the accuracy and practicability of the required monitoring systems, and economics. The FOCCUS trial examined perioperative fluid optimization with a very basic approach: a standardized volume load with 25 ml/kg crystalloids over 6 hours immediately prior to scheduled surgery in high-risk patients. The hypothesis was that this intervention would lead to a compensation of preoperative fluid deficit caused by overnight fasting, and would result in improved perioperative fluid homeostasis with less postoperative complications and earlier hospital discharge. However, the primary study endpoints did not improve significantly. This observation points towards the facts that: firstly, the differentiation between interstitial fluid deficit caused by fasting and intravascular volume loss due to acute blood loss must be recognized in treatment strategies; secondly, the type of fluid replacement may play an important role; and thirdly, protocolized treatment strategies should also always be tailored to suit the patients' individual needs in every individual clinical situation.
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Effect of acute hyperventilation on the venous-arterial PCO2 difference
I read with great interest the article by Morel et al. [1], suggesting that acute changes in the arterial partial pressure of carbon dioxide (PaCO2) can affect the venous-arterial difference in carbon dioxide tension ([increment]CO2). Ten ventilated and hemodynamically stable patients were included after elective cardiac surgery. Hypocapnia was induced by increasing of respiratory rate. The authors found that a decrease of PaCO2 was associated with a significant increase in [increment]CO2. This was explained by the fact that acute hypocapnia resulted in systemic vasoconstriction, thus decreasing the elimination of the total CO2 produced by the peripheral tissues, and therefore increased the gap. However, as all patients were monitored with a pulmonary artery catheter (PAC), the authors should have shown if there were any increase in systemic vascular resistance to support their hypothesize. Furthermore, there is a possible another explanation of the increase of [increment]CO2 induced by the decrease in PaCO2. Indeed, acute respiratory alkalosis has been shown to increase systemic oxygen consumption and CO2 production [2,3]. Thus, for a given venous blood flow the increase of tissue CO2 production should increase the PCO2 gap.On the other hand, it is unclear why the authors have used the central venous sample to calculate [increment]CO2 instead of the mixed venous sample (PAC), which is the gold standard. If a PAC is in place, even though the mixed and central PCO2 difference showed a good agreement [4], the clinical utility of an alternative method of measurement is diminished. Nevertheless, I agree that acute hyperventilation could be a potential limitation of clinical application of the [increment]CO2.
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Low doses of esmolol and phenylephrine act as diuretics during intravenous anesthesia
IntroductionThe renal clearance of infused crystalloid fluid is very low during anaesthesia and surgery, but experiments in conscious sheep indicate that the renal fluid clearance might approach a normal rate when the adrenergic balance is modified.
Methods:
60 females (mean age, 32 years) undergoing laparoscopic gynecological surgery were randomized to control group and received only the conventional anesthetic drugs and 20 ml/kg of lactated Ringer's over 30 mins. The others were also given an infusion of 50 ug/kg/min of esmolol (beta1-receptor blocker) or 0.01 ug/kg/min of phenylephrine (alpha1-adrenergic agonist) over 3 hours. The distribution and elimination of infused fluid was studied by volume kinetic analysis based on urinary excretion and blood hemoglobin level.
Results:
Both drugs significantly increased urinary excretion while heart rate and arterial pressure remained largely unaffected. The urine flow during non-surgery was 43, 147, and 176 ml in the control, esmolol, and phenylephrine groups, respectively (medians, P<0.03). When surgery had started the corresponding values were 34, 65 and 61 ml (P<0.04). At 3 hours, an average of 9%, 20%, and 25% of the infused volume had been excreted in the three groups (P<0.01). The kinetic analyses indicated that both treatments slowed down the distribution of fluid from the plasma to the interstitial fluid space, thereby preventing hypovolemia.
Conclusions:
Esmolol doubled and phenylephrine almost tripled urinary excretion during anesthesia-induced depression of renal fluid clearance.
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Use of carperitide infusion for acutely decompensated heart failure
In our retrospective observational study, carperitide had higher improvement rate of functional class, though some reports have been against the use of nesiritide in acute heart failure patients. Also, the use of carperitide was not associated with death or heart failure admission after adjustment. Carperitide compares favorably to nesiritide in several ways; it has a shorter half-life, does not mandate bolus infusion, and used mostly as a single agent. We surmise that these unique pharmacological profiles may be part of the reasons for the difference in outcomes and the use of carperitide should be judiciously evaluated in prospective trials.Key words: carperitide, nesiritide, acute heart failure
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Passive immunotherapy of sepsis with intravenous immune globulin: not all IVIg preparations are created equal
Normal intravenous immunoglobulin (IVIg) preparations are potentially promising drugs for the adjunctive treatment of sepsis as the pool of IgG antibodies neutralizes a wide array of pathogens plus their virulence factors and in addition possesses broad anti-inflammatory and immunomodulating activities. However, several high quality clinical studies have failed to show an effect of IVIg therapy on survival of sepsis patients. The reason behind this lack of success could be that the wrong immunoglobulin preparations have been used so far. We review evidence from experimental sepsis studies proving that licensed IVIg with additionally enhanced antigen-binding polyspecificity have significant beneficial effects in all sepsis models used.
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A critique of fluid bolus resuscitation in severe sepsis
Resuscitation of septic patients by means of one or more fluid boluses is recommended by guidelines from multiple relevant organizations and as a component of surviving sepsis campaigns. The technique is considered a key and life-saving intervention during the initial treatment of severe sepsis in children and adults. Such recommendations, however, are only based on expert opinion and lack adequate experimental or controlled human evidence. Despite these limitations, fluid bolus therapy (20 to 40 ml/kg) is widely practiced and is currently considered a cornerstone of the management of sepsis. In this pointof-view critique, we will argue that such therapy has weak physiological support, has limited experimental support, and is at odds with emerging observational data in several subgroups of critically ill patients or those having major abdominal surgery. Finally, we will argue that this paradigm is now challenged by the findings of a large randomized controlled trial in septic children. In the present article, we contend that the concept of large fluid bolus resuscitation in sepsis needs to be investigated further.
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Descending aortic calcification increases renal dysfunction and in-hospital mortality in cardiac surgery patients with intraaortic balloon pump counterpulsation placed perioperatively: a case control study
IntroductionAcute kidney injury (AKI) after cardiac surgery increases length of hospital stay and in-hospital mortality. A significant number of patients undergoing cardiac surgical procedures require perioperative intra-aortic balloon pump (IABP) support. Use of an IABP has been linked to an increased incidence of perioperative renal dysfunction and death. This might be due to dislodgement of atherosclerotic material in the descending thoracic aorta (DTA). Therefore, we retrospectively studied the correlation between DTA atheroma, AKI and in hospital mortality.
Methods:
454 patients were retrospectively matched to one of four groups: -IABP/-DTA atheroma, +IABP/-DTA atheroma, -IABP/+DTA atheroma, +IABP/+DTA atheroma. Patients were then matched according to presence/absence of DTA atheroma, presence /absence of IABP, performed surgical procedure, age, gender and left ventricular ejection fraction (LVEF). DTA atheroma was assessed through standard transesophageal echocardiography (TEE) imaging studies of the descending thoracic aorta.
Results:
Basic patient characteristics, except for age and gender, did not differ between groups. Perioperative AKI in patients with -DTA atheroma/+IABP was 5.1% vs. 1.7 % in patients with -DTA atheroma/-IABP. In patients with +DTA atheroma/+IABP the incidence of AKI was 12.6% vs. 5.1% in patients with +DTA atheroma/-IABP. In-hospital mortality in patients with +DTA atheroma/-IABP was 3.4% vs. 8.4% with +DTA atheroma/+IABP. In patients with +DTA atheroma/+IABP in hospital mortality was 20.2% vs. 6.4% with +DTA atheroma/-IABP. Multivariable logistic regression identified DTA atheroma > 1mm (P = *0.002, OR= 4.13, CI= 1.66 to 10.30), as well as IABP support (P = *0.015, OR= 3.04,CI= 1.24 to 7.45) as independent predictors of perioperative AKI and increased in-hospital mortality. DTA atheroma in conjunction with IABP significantly increased the risk of developing acute kidney injury (P = 0.0016) and in-hospital mortality (P = 0.0001) when compared to control subjects without IABP and without DTA atheroma.
Conclusions:
Perioperative IABP and DTA atheroma are independent predictors of perioperative AKI and in-hospital mortality. Whether adding an IABP in patients with severe DTA calcification increases their risk of developing AKI and mortality postoperatively cannot be clearly answered in this study. Nevertheless, when IABP and DTA are combined, patients are more likely to develop AKI and to die postoperatively in comparison to patients without IABP and DTA atheroma.
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Diagnostic Pathology - Latest Articles
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EGFR, CD10 and proliferation marker Ki67 expression in Ameloblastoma: possible role in local recurrence
Background:
Ameloblastoma is an odontogenic neoplasm characterized by local invasiveness and tendency towards recurrence.AimsStudying the role played by EGFR, CD10 and Ki67 in the recurrence of ameloblastoma.
Methods:
This study was carried out on 22 retrospective cases of mandibular ameloblastoma from the period from Jan 2002 to Jan 2008 with follow up period until Jan 2011 (minimal 3 years follow up). Archival materials were obtained from pathology department, Mansoura university. Paraffin sections of tumor tissue from all cases were submitted for routine H&E stains and immunohistochemistry using EGFR, CD10 and Ki67 monoclonal antibodies.Statistical analysis using of clinical data for all patients, tumor type, EGFR, CD10 and Ki67 expression in relation to recurrence were evaluated.
Results:
Among the 22 cases, 10 cases were males and 12 were females with sex ratio 1:1.2. Age ranged from 30 to 60 years old with a mean age 48 year. Five cases showed local recurrence within studied period and proved by biopsy. No statistically significant relation was found between local recurrence and patient age, tumor size, tumor type, EGFR expression. There was a significant relation between CD10 expression as well as Ki67 labelling index and recurrence (P value =0.003, 0.000 respectively).
Conclusion:
Evaluation of CD10 and Ki67 status together with conventional histological evaluation can help in providing more information about the biologic behavior of the tumor, while EGFR could be a target of an expanding class of anticancer therapies.Since ameloblastomas are EGFR-positive tumors, anti-EGFR agents could be considered to reduce the size of large tumors and to treat unresectable tumors that are in close proximity to vital structures.
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Worldwide variations in EGFR somatic mutations: a challenge for personalized medicine
Two studies recently reported around 10% of EGFR activating mutations in triple negative breast cancers from Asian patients. However, we did not find any EGFR activating mutation in a series of 229 breast tumor samples from European patients. Like in lung cancer, the EGFR mutation profiles seem to be related to the ethnical origin of patients. This is an important point that should be considered when developing anti-EGFR therapies.
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CD163 Versus CD68 in Tumor Associated Macrophages of Classical Hodgkin Lymphoma
Classical Hodgkin lymphoma (CHL) is a B-cell lymphoproliferative disorder with a relatively good prognosis. A small but significant percentage of patients, however, will respond poorly to therapy. A recent gene expression profiling study has identified a macrophage signature which has been correlated with primary treatment failure, and immunohistochemical tissue microarray for CD68 was shown to reflect the gene signature as a potentially clinically useful marker to predict adverse prognosis.We examined 44 cases of CHL, mostly nodular sclerosis subtype, in which the immunohistochemical stains for the histiocytic markers CD68 and CD163 were performed. The staining intensity was graded for each stain (<5, 5-25, and >25 percent of cells positive in the Hodgkin cell (HC) rich nodules) and background staining characteristics were recorded.CD163 staining was lower than CD68 in HC rich nodules, with lower background staining (p 0.03). There was no significant difference between either CD68 or CD163 and disease recurrence in a subset (N=41) of cases.In conclusion, we demonstrate that CD163 staining is lower than CD68, with less non-specific staining of background inflammatory cells and Hodgkin cells, therefore is a better marker for tumor associated macrophages. However, we did not identify a correlation between staining for CD68 or CD163 and recurrence of disease.Virtual slidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1460518258831620
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Brain MRI and biological diagnosis in five Tunisians MLD patients
Metachromatic leukodystrophy (MLD) is a recessive autosomal disease which is characterized by an accumulation of sulfatides in the central and peripheral nervous system. It is due to the enzyme deficiency of the sulfatide sulfatase i.e. arylsulfatase A (ASA).we studied 5/200 cases of MLD and clearly distinguished three clinical forms. One of them presented the juvenile form; two presented the late infantile form; and two other presented the adult form. The Magnetic Resonance Imaging (MRI) of these patients showed a diffuse, bilateral and symmetrical demyelination. The biochemical diagnosis of MLD patients evidencing the low activity of ASA and sulfatide accumulation.Keys words: arylsulfatase A, urinary sulfatide, sulfatide, demylinisation, metachromatic leukodystrophy.Patients and methods: We studied 5/200 MLD patients addressed to us for behavioral abnormalities and progressive mental deterioration. All of them were diagnosed at first by brain MRI evidencing a bilateral demyelination, then the measurement of ASA activity using P-nitrocathecol sulfate as substrate, finally the sulfatiduria was performed using thin-layer chromatography using alpha-naphtol reagent.
Results:
In this study, from 200 patients presenting behavioral abnormalities and a progressive mental deterioration, we reported just 2patients were diagnosed as late-infantile form of MLD. Only1 case presented as the juvenile form; and 2 patients with the adult-type of MLD. The brain magnetic resonance imaging (MRI) of all patients showed characteristic lesions of MLD with extensive demyelination. Biochemical investigations of these patients detected a low level of ASA activity at 0degreesC and 37degreesC; the excess of sulfatide in sulfatiduria.
Conclusion:
MRI is required to orient the diagnosis of MLD patients; the latter must be confirmed by the biochemical investigations which is based on the measurement of ASA activity and the excess of sulfatide showed in the sulfatiduria.Virtual slides:The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1791578262610232
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Carcinoma involving the gallbladder: A retrospective review of 23 cases - pitfalls in diagnosis of gallbladder carcinoma
Background:
Carcinoma of the gallbladder (GBC) clinically mimics benign gallbladder diseases and often escapes detection until advanced stage. Despite the frequency of cholecystectomy, diagnosis of GBC remains problematic in many situations. We sought to identify pathologic features that contribute to the difficulty in recognition of GBC.
Methods:
We identified 23 patients (ranged from 45 to 86 years, male to female ratio 1:4.5) with carcinoma involving the gallbladder referred to an academic medical center over a period of 10 years for study. This includes 10 cases of primary GBC, 6 cases of metastatic tumor to gallbladder, 6 cases of directly invasive adenocarcinoma arising elsewhere in the biliary tree, and one case of unidentified origin adenocarcinoma. Primary tumors include adenocarcinoma not otherwise specified (NOS) in 6 cases, papillary adenocarcinoma in 2 cases, and single cases of undifferentiated carcinoma and combined adenocarcinoma and neuroendocrine carcinoma (NEC). Metastatic tumors to gallbladder were from a wide range of primary sites, predominantly the gastrointestinal tract.
Results:
These cases illustrate seven potential pitfalls which can be encountered. These include: 1) mistakenly making a diagnosis of adenocarcinoma of gallbladder when only benign lesions such as deeply penetrating Rokitansky-Aschoff sinuses are present (overdiagnosis), 2) misdiagnosing well-differentiated invasive carcinoma with minimal disease as benign disease (underdiagnosis), 3) differentiating between primary NEC of gallbladder and metastasis, 4) confusing primary mucinous adenocarcinoma of gallbladder with pseudomyxoma peritonei from a low grade appendiceal neoplasm disseminated to gallbladder, 5) confusing gangrenous necrosis related to cholecystitis with geographic tumoral necrosis, 6) undersampling early, grossly occult disease, and 7) misinterpreting extracellular mucin pools.
Conclusions:
Clinical history and a high index of suspicion are prerequisite to detecting GBC. Detection of GBC at an early stage is difficult because the symptoms mimic benign gallbladder diseases. Misinterpretation of subtle microscopic abnormalities contributes diagnostic failures in early cases. Careful attention to any evidence of mural thickening, thorough sampling, particularly in older patients, and close examination of any deeply situated glandular structures are critical. Correlations with radiographic and clinical findings are important helps to avoid misdiagnosis in this commonly resected organ.
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The value of CDX2 and cytokeratins 7 and 20 expression in differentiating colorectal adenocarcinomas from extraintestinal gastrointestinal adenocarcinomas: cytokeratin 7/20+ phenotype is more spesific than CDX2 antibody
Background/Objective: Metastatic adenocarcinoma from an unknown primary site is a common clinical problem. Determining the cytokeratin (CK) 7/CK20 pattern of tumors is one of the most helpful procedures for this purpose since the CK7/CK20+ pattern is typical of colorectal adenocarcinomas. CDX2, a critical nuclear transcription factor for intestinal development, is expressed in intestinal epithelium and adenocarcinomas. In the present study, we compared the sensitivity and specificity of CDX2 expression and the CK7/CK20+ phenotype in differentiating colorectal adenocarcinomas from pancreatic and gastric adenocarcinomas.
Methods:
CK7/CK20 staining pattern and CDX2 expression were evaluated in 118 cases of colorectal, 59 cases of gastric, and 32 cases of pancreatic adenocarcinomas. The sensitivity, specificity, and positive and negative predictive values of the CK7/CK20+ phenotype and of CDX2 expression were analyzed.
Results:
The CK7/CK20+ immunophenotype was expressed by 75 of 118 (64%) colorectal and 3 of 59 (5%) gastric tumors and was not observed in any pancreatic adenocarcinomas. The CK7+/CK20+ immunophenotype was expressed in 24/118 (20%) of colon, 28/59 (48%) of gastric and 7/32 (22%) of pancreatic adenocarcinomas. The CK7+/CK20 expression pattern was observed in only 2% (2 of 118) of colorectal carcinomas. CDX2 was expressed in 114 of 118 (97%) colorectal, 36 of 59 (61%) gastric, and 5 of 32(16%) pancreatic adenocarcinomas. There was no significant association between CDX2 expression and tumor differentiation in colorectal carcinomas. In gastric carcinomas, CDX2 expression was more common in intestinal type tumors than in diffuse type carcinomas. The CK7/CK20+ phenotype showed a specificity of 96.7% in predicting colorectal adenocarcinomas, which was superior to that of CDX2 expression. CDX2 expression at both cut-off levels (5% and 50%) had a higher sensitivity (96.6% and 78%) than the CK phenotype.
Conclusions:
Both the CK7/CK20+ phenotype and expression of the antibody CDX2 are highly specific and sensitive markers of colorectal origin. CDX2 expression should be a useful adjunct for the diagnosis of intestinal adenocarcinomas, particularly when better established markers such as CK7 and CK20 yield equivocal results. The CK7/CK20+ phenotype is superior in its specificity and positive predictive value and might be preferred.Virtual slides:The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/4851011866354821
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Concurrent hypermethylation of DNMT1, MGMT and EGFR genes in progression of gliomas
Background:
Gliomas are the most common neoplasm of the brain. High-grade gliomas often resist treatment even with aggressive surgical resection and adjuvant radiation and chemotherapy. Despite the combined treatment, they frequently recur with the same or higher-grade histology. Genetic instability is commonly associated with inactivation of the normal DNA repair function and tumour suppressor genes as well as activation of oncogenes resulting from alterations of promoter hypermethylation, but the molecular mechanisms of the histological and clinical progression of gliomas are still poorly understood.
Methods:
This study involved longitudinal analysis samples of primary and recurrent gliomas to determine whether the progression of low- and high-grade gliomas is associated with the promoter methylation of the DNMT1, MGMT and EGFR genes by PCR-based restriction enzyme assay. Epigenetic inactivation of these three important glioma-associated genes was analyzed in paired biopsy samples from 18 patients with tumour recurrence.
Results:
The methylation analysis of the CpG sites in the DNA methyltransferase (DNMT1) promoter revealed a total of 6 hypermethylations (6/18), the methylguanine-DNA methyltransferase (MGMT) promoter revealed a total of 10 hypermethylations (10/18) and the epithelial grow factor receptor (EGFR) promoter revealed a total of 12 (12/18) hypermethylations respectively in recurrent gliomas. The results demonstrated that DNMT1 promoter hypermethylation does not occur in low-grade gliomas, it was mainly observed in secondary glioblastomas. Additionally, the MGMT and EGFR promoter was hypermethylated in both low- and high-grade GLs and their corresponding histological transformed GLs.
Conclusion:
This study has provided further evidence that the histological transformation and progression of gliomas may be associated with the inactivation of the EGFR and MGMT genes. It seems that EGFR and MGMT promoter hypermethylations are early events in the clonal evolution of gliomas and this gene inactivation has proved to be stable even in tumour recurrence. However, the DNMT hypermethylation is a late part of glioma progression.Virtual slides: The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1935054011612460
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Secondary cutaneous Epstein-Barr virus-associated diffuse large B-cell lymphoma in a patient with angioimmunoblastic T-cell lymphoma: a case report and review of literature
Only a few cases of extranodal Epstein-Barr virus (EBV)-associated B-cell lymphomas arising from patients with angioimmunoblastic T-cell lymphoma (AITL) have been described. We report a case of AITL of which secondary cutaneous EBV-associated diffuse large B-cell lymphoma (DLBCL) developed after the initial diagnosis of AITL. A 65-year-old Chinese male patient was diagnosed as AITL based on typical histological and immunohistochemical characteristics in biopsy of the enlarged right inguinal lymph nodes. The patient initially received 6 cycles of chemotherapy with CHOP regimen (cyclophosphamide, vincristine, adriamycin, prednisone), but his symptoms did not disappear. Nineteen months after initial diagnosis of AITL, the patient was hospitalized again because of multiple plaques and nodules on the skin. The skin biopsy was performed, but this time the tumor was composed of large, polymorphous population of lymphocytes with CD20 and CD79a positive on immunohistochemical staining. The tumor cells were strong positive for EBER by in situ hybridization. The findings of skin biopsy were compatible with EBV-associated DLBCL. CHOP-R chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab) was then administered, resulting in partial response of the disease with pancytopenia and suppression of cellular immunity. To our knowledge, this is the first case of cutaneous EBV-associated DLBCL originated from AITL in Chinese pepole. We suggest the patients with AITL should perform lymph node and skin biopsies regularly in the course of the disease to detect the progression of secondary lymphomas.Virtual slidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1197421158639299
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Mechanisms of Cyst Formation in Metastatic Lymph Nodes of Head
and Neck Squamous Cell Carcinoma
Cystic change in metastatic lymph nodes occurs in certain types of tumors and mostly in squamous cell carcinoma of the head and neck. In the majority of cases, psuedocystic change is the mechanism of cyst formation. However, sometimes a true cyst cavity is formed. This occurrence is unexplained and some theories are introduced to explain it. In this paper, related articles and introduced concepts are reviewed and the best conclusions of present hypotheses are provided. Cystic SCC in cervical lymph node is now considered as a typical presentation of metastatic SCC arising in the oro/nasopharynx. True cystic cavities have eosinophilic fluid content and present active transport mechanism across the epithelium; Cytokeratin7 is also expressed in the lining of these cysts, which is an accepted marker of ductal differentiation. These are all strong evidences that show salivary gland type cells are present among tumor cells. In fact, some squamous cell carcinomas, especially those arising in Waldeyer's ring, originate from minor salivary glands. The other probability is that these tumors are cancers of transitional type and arise from transformed keratinocytes, which have intrinsic property for cyst formation. These malignant cells in lymph nodes, rather than primary sites, found the opportunity to express their parental property.Virtual slides: The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/6838476096250792
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Expression of GSK-3beta in Renal Allograft Tissue and Its Significance in Pathogenesis of Chronic Allograft Dysfunction
ObjectiveTo explore the expression of Glycogen synthase kinase 3 beta (GSK-3beta) in renal allograft tissue and its significance in the pathogenesis of chronic allograft dysfunction.
Methods:
Renal allograft biopsy was performed in all of the renal allograft recipients with proteinuria or increased serum creatinine level who came into our hospital from January 2007 to December 2009. Among them 28 cases was diagnosed as chronic allograft dysfunction based on pahtological observation, including 21 males with a mean age of 45+/-10 years old and 7 females with a mean age of 42+/-9 years old. The time from kidney transplantation to biopsy were 1-9 (3.5) years. Their serum creatinine level were 206+/-122 umol/L. Immunohistochemical assay and computer-assisted genuine color image analysis system (imagepro-plus 6.0) were used to detect the expression of GSK-3beta in the renal allografts of 28 cases of recipients with chronic allograft dysfunction. Mean area and mean integrated optical density of GSK-3beta expression were calculated. The relationship between expression level of GSK-3beta and either the grade of inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft was analyzed. Five specimens of healthy renal tissue were used as controls.
Results:
The expression level of the GSK-3beta was significantly increased in the renal allograft tissue of recipients with chronic allograft dysfunction, compared to normal renal tissues, and GSK-3beta expression became stronger along with the increasing of the grade of either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft tissue.
Conclusion:
There might be a positive correlation between either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy and high GSK-3beta expression in renal allograft tissue.Virtual slides: The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/9924478946162998
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Emerging Themes in Epidemiology - Latest Articles
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Using Geographical Information Systems Mapping to Identify Areas Presenting High Risk for Traumatic Brain Injury
Background:
The aim of this study is to show how geographical information systems (GIS) can be used to track and compare hospitalization rates for traumatic brain injury (TBI) over time and across a large geographical area using population based data.Results & DiscussionData on TBI hospitalizations, and geographic and demographic variables, came from the Ontario Trauma Registry Minimum Data Set for the fiscal years 1993-1994 and 2001-2002. Various visualization techniques, exploratory data analysis and spatial analysis were employed to map and analyze these data. Both the raw and standardized rates by age/gender of the geographical unit were studied. Data analyses revealed persistent high rates of hospitalization for TBI resulting from any injury mechanism between two time periods in specific geographic locations.
Conclusions:
This study shows how geographic information systems can be successfully used to investigate hospitalizaton rates for traumatic brain injury using a range of tools and techniques; findings can be used for local planning of both injury prevention and post discharge services, including rehabilitation.
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What do we have to know from migrants' past exposures to understand their health status? A life course approach
Empirical findings show that morbidity and mortality risks of migrants can differ considerably from those of populations in the host countries. However, while several explanatory models have been developed, most migrant studies still do not consider explicitly the situation of migrants before migration. Here, we discuss an extended approach to understand migrant health comprising a life course epidemiology perspective.The incorporation of a life course perspective into a conceptual framework of migrant health enables the consideration of risk factors and disease outcomes over the different life phases of migrants, which is necessary to understand the health situation of migrants and their offspring. Comparison populations need to be carefully selected depending on the study questions under consideration within the life course framework.Migrant health research will benefit from an approach using a life course perspective. A critique of the theoretical foundations of migrant health research is essential for further developing both the theoretical framework of migrant health and related empirical studies.
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Assessing causal relationships in genomics:
From Bradford-Hill criteria to complex gene-environment interactions and directed acyclic graphs
Observational studies of human health and disease (basic, clinical and epidemiological) are vulnerable to methodological problems -such as selection bias and confounding- that make causal inferences problematic. Gene-disease associations are no exception, as they are commonly investigated using observational designs. A rich body of knowledge exists in medicine and epidemiology on the assessment of causal relationships involving personal and environmental causes of disease; it includes seminal causal criteria developed by Austin Bradford Hill and more recently applied directed acyclic graphs (DAGs). However, such knowledge has seldom been applied to assess causal relationships in clinical genetics and genomics, even in studies aimed at making inferences relevant for human health. Conversely, incorporating genetic causal knowledge into clinical and epidemiological causal reasoning is still a largely unexplored area.As the contribution of genetics to the understanding of disease aetiology becomes more important, causal assessment of genetic and genomic evidence becomes fundamental. The method we develop in this paper provides a simple and rigorous first step towards this goal. The present paper is an example of integrative research, i.e., research that integrates knowledge, data, methods, techniques, and reasoning from multiple disciplines, approaches and levels of analysis to generate knowledge that no discipline alone may achieve.
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Defining neurotrauma in administrative data using the International Classification of Diseases Tenth Revision
Background:
It is essential to use a definition that is precise and accurate for the surveillance of traumatic brain injuries (TBI) and spinal cord injuries (SCI). This paper reviews the International Classification of Diseases 10th revision (ICD-10) definitions used internationally to inform the definition for neurotrauma surveillance using administrative data in Ontario, Canada.
Methods:
PubMed, Web of Science, Medline and the grey literature were searched for keywords "spinal cord injuries" or "brain injuries" and "international classification of diseases". All papers and reports that used an ICD-10 definition were included. To determine the ICD-10 codes for inclusion consensus across papers and additional evidence were sought to look at the correlation between the condition and brain or spinal injuries.
Results:
Twenty-four articles and reports were identified; 15 unique definitions for TBI and 7 for SCI were found. The definitions recommended for use in Ontario by this paper are F07.2, S02.0, S02.1, S02.3, S02.7, S02.8, S02.9, S06, S07.1, T90.2, and T90.5 for traumatic brain injuries and S14.0, S14.1, S24.0, S24.1, S34.1, S34.0, S34.3, T06.0, T06.1 and T91.3 for spinal cord injuries.
Conclusions:
Internationally, inconsistent definitions are used to define brain and spinal cord injuries. An abstraction study of data would be an asset in understanding the effects of inclusion and exclusion of codes in the definition. This paper offers a definition of neurotrauma for surveillance in Ontario, but the definition could be applied to other countries that have mandated administrative data collection.
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Relative survival: a useful tool to assess generalisability in longitudinal studies of health in older persons
Background:
Generalisability of longitudinal studies is threatened by issues such as choice of sampling frame, representativeness of the initial sample, and attrition. To determine representativeness, cohorts are often compared with the population of interest at baseline on demographic and health characteristics. This study illustrates the use of relative survival as a tool for assessing generalisability of results from a cohort of older people among whom death is a potential threat to generalisability.
Methods:
The authors used data from the 1921-26 cohort (n = 12,416, aged 70-75 in 1996) of the Australian Longitudinal Study on Women's Health (ALSWH). Vital status was determined by linkage to the National Death Index, and expected deaths were derived using Australian life tables. Relative survival was estimated using observed survival in the cohort divided by expected survival among women of the same age and State or Territory.
Results:
Overall, the ALSWH women showed relative survival 9.5% above the general population. Within States and Territories, the relative survival advantage varied from 6% to 23%. The interval-specific relative survival remained relatively constant over the 12 years (1996-2008) under review, indicating that the survival advantage of the cohort has not diminished over time.
Conclusion:
This study demonstrates that relative survival can be a useful measure of generalisability in a longitudinal study of the health of the general population, particularly when participants are older.
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Conceptualizing population health: from mechanistic thinking to complexity science
The mechanistic interpretation of reality can be traced to the influential work by René Descartes and Sir Isaac Newton. Their theories were able to accurately predict most physical phenomena relating to motion, optics and gravity. This paradigm had at least three principles and approaches: reductionism, linearity and hierarchy. These ideas appear to have influenced social scientists and the discourse on population health. In contrast, Complexity Science takes a more holistic view of systems. It views natural systems as being 'open', with fuzzy borders, constantly adapting to cope with pressures from the environment. These are called Complex Adaptive Systems (CAS). The sub-systems within it lack stable hierarchies, and the roles of agency keep changing. The interactions with the environment and among sub-systems are non-linear interactions and lead to self-organisation and emergent properties. Theoretical frameworks such as epi+demos+cracy and the ecosocial approach to health have implicitly used some of these concepts of interacting dynamic sub-systems. Using Complexity Science we can view population health outcomes as an emergent property of CAS, which has numerous dynamic non-linear interactions among its interconnected sub-systems or agents. In order to appreciate these sub-systems and determinants, one should acquire a basic knowledge of diverse disciplines and interact with experts from different disciplines. Strategies to improve health should be multi-pronged, and take into account the diversity of actors, determinants and contexts. The dynamic nature of the system requires that the interventions are constantly monitored to provide early feedback to a flexible system that takes quick corrections.
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The democratic fallacy in matters of clinical opinion: implications for analysing cause-of-death data
Arriving at a consensus between multiple clinical opinions concerning a particular case is a complex issue - and may give rise to manifestations of the democratic fallacy, whereby a majority opinion is misconstrued to represent some kind of "truth" and minority opinions are somehow "wrong". Procedures for handling multiple clinical opinions in epidemiological research are not well established, and care is needed to avoid logical errors. How to handle physicians' opinions on cause of death is one important domain of concern in this respect. Whether multiple opinions are a legal requirement, for example ahead of cremating a body, or used for supposedly greater rigour, for example in verbal autopsy interpretation, it is important to have a clear understanding of what unanimity or disagreement in findings might imply, and of how to aggregate case data accordingly.In many settings where multiple physicians have interpreted verbal autopsy material, an over-riding goal of arriving at a single cause of death per case has been applied. In many instances this desire to constrain findings to a single cause per case has led to methodologically awkward devices such as "TB/AIDS" as a single cause. This has also usually meant that no sense of disagreements or uncertainties at the case level is taken forward into aggregated data analyses, and in many cases an "indeterminate" cause may be recorded which actually reflects a lack of agreement rather than a lack of data on possible cause(s).In preparing verbal autopsy material for epidemiological analyses and public health interpretations, the possibility of multiple causes of death per case, and some sense of any disagreement or uncertainty encountered in interpretation at the case level, need to be captured and incorporated into overall findings, if evidence is not to be lost along the way. Similar considerations may apply in other epidemiological domains.
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Comparison of two approaches for measuring household wealth via an asset-based index in rural and peri-urban settings of Hunan province, People's Republic of China
Background:
There are growing concerns regarding inequities in health, with poverty being an important determinant of health as well as a product of health status. Within the People's Republic of China (P.R. China), disparities in socio-economic position are apparent, with the rural-urban gap of particular concern. Our aim was to compare direct and proxy methods of estimating household wealth in a rural and a peri-urban setting of Hunan province, P.R. China.
Methods:
We collected data on ownership of household durable assets, housing characteristics, and utility and sanitation variables in two village-wide surveys in Hunan province. We employed principal components analysis (PCA) and principal axis factoring (PAF) to generate household asset-based proxy wealth indices. Households were grouped into quartiles, from 'most wealthy' to 'most poor'. We compared the estimated household wealth for each approach. Asset-based proxy wealth indices were compared to those based on self-reported average annual income and savings at the household level.
Results:
Spearman's rank correlation analysis revealed that PCA and PAF yielded similar results, indicating that either approach may be used for estimating household wealth. In both settings investigated, the two indices were significantly associated with self-reported average annual income and combined income and savings, but not with savings alone. However, low correlation coefficients between the proxy and direct measures of wealth indicated that they are not complementary. We found wide disparities in ownership of household durable assets, and utility and sanitation variables, within and between settings.
Conclusion:
PCA and PAF yielded almost identical results and generated robust proxy wealth indices and categories. Pooled data from the rural and peri-urban settings highlighted structural differences in wealth, most likely a result of localized urbanization and modernization. Further research is needed to improve measurements of wealth in low-income and transitional country contexts.
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Effect of an armed conflict on relative socioeconomic position of rural households: case study from western Cote d'Ivoire
Background:
Current conceptual frameworks on the interrelationship between armed conflict and poverty are based primarily on aggregated macro-level data and/or qualitative evidence and usually focus on adherents of warring factions. In contrast, there is a paucity of quantitative studies about the socioeconomic consequences of armed conflict at the micro-level, i.e., noncommitted local households and civilians.
Methods:
We conducted a secondary analysis of data pertaining to risk factors for malaria and neglected tropical diseases. Standardized questionnaires were administered to 182 households in a rural part of western Côte d'Ivoire in August 2002 and again in early 2004. Between the two surveys, the area was subject to intensive fighting in the Ivorian civil war. Principal component analysis was applied at the two time points for constructing an asset-based wealth-index and categorizing the households in wealth quintiles. Based on quintile changes, the households were labeled as 'worse-off', 'even' or 'better-off'. Statistical analysis tested for significant associations between the socioeconomic fates of households and head of household characteristics, household composition, village characteristics and self-reported events associated with the armed conflict. Most-poor/least-poor ratios and concentration indices were calculated to assess equity changes in households' asset possession.
Results:
Of 203 households initially included in the first survey, 21 were lost to follow-up. The population in the remaining 182 households shrunk from 1,749 to 1,625 persons due to migration and natural population changes. However, only weak socioeconomic dynamics were observed; every seventh household was defined as 'worse-off' or 'better-off' despite the war-time circumstances. Analysis of other reported demographic and economic characteristics did not clearly identify more or less resilient households, and only subtle equity shifts were noted.However, the results indicate significant changes in livelihood strategies with a significant return to agricultural production and a decrease in the diversity of socioeconomic activities.
Conclusion:
Situational constraints and methodological obstacles are inherent in conflict settings and hamper conflict-related socioeconomic research. Furthermore, sensitive methods to assess and meaningfully interpret longitudinal micro-level wealth data from low-income countries are lacking. Despite compelling evidence of socioeconomic dynamics triggered by armed conflicts at the macro-level, we could not identify similar effects at the micro-level. A deeper understanding of household profiles that are more resilient to armed conflict could help to better prevent and/or alleviate adverse conflict-related and increasingly civilian-borne socioeconomic effects.
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Sampling strategies to measure the prevalence of common recurrent infections in longitudinal studies
Background:
Measuring recurrent infections such as diarrhoea or respiratory infections in epidemiological studies is a methodological challenge. Problems in measuring the incidence of recurrent infections include the episode definition, recall error, and the logistics of close follow up. Longitudinal prevalence (LP), the proportion-of-time-ill estimated by repeated prevalence measurements, is an alternative measure to incidence of recurrent infections. In contrast to incidence which usually requires continuous sampling, LP can be measured at intervals. This study explored how many more participants are needed for infrequent sampling to achieve the same study power as frequent sampling.
Methods:
We developed a set of four empirical simulation models representing low and high risk settings with short or long episode durations. The model was used to evaluate different sampling strategies with different assumptions on recall period and recall error.
Results:
The model identified three major factors that influence sampling strategies: (1) the clustering of episodes in individuals; (2) the duration of episodes; (3) the positive correlation between an individual's disease incidence and episode duration. Intermittent sampling (e.g. 12 times per year) often requires only a slightly larger sample size compared to continuous sampling, especially in cluster-randomized trials. The collection of period prevalence data can lead to highly biased effect estimates if the exposure variable is associated with episode duration. To maximize study power, recall periods of 3 to 7 days may be preferable over shorter periods, even if this leads to inaccuracy in the prevalence estimates.
Conclusion:
Choosing the optimal approach to measure recurrent infections in epidemiological studies depends on the setting, the study objectives, study design and budget constraints. Sampling at intervals can contribute to making epidemiological studies and trials more efficient, valid and cost-effective.
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Environmental Health - Latest Articles
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Prostate cancer and toxicity from critical use exemptions of methyl bromide: Environmental protection helps protect against human health risks
Background:
Although ozone-depleting methyl bromide was destined for phase-out by 2005, it is still widely applied as a consequence of various critical-use-exemptions and mandatory international regulations aiming to restrict the spread of pests and alien species (e.g. in globalized transport and storage). The withdrawal of methyl bromide because of its environmental risk could fortuitously help in the containment of its human toxicity.
Methods:
We performed a systematic review of the literature, including in vitro toxicological and epidemiological studies of occupational and community exposure to the halogenated hydrocarbon pesticide methyl bromide. We focused on toxic (especially chronic) or carcinogenic effects from the use of methyl bromide, on biomonitoring data and reference values. Eligible epidemiological studies were subjected to meta-analysis.
Results:
Out of the 542 peer reviewed publications between 1990 and 2011, we found only 91 referring to toxicity of methyl bromide and 29 using the term "carcinogenic", "neoplastic" or "mutagenic". Several studies provide new additional data pertaining to the mechanistic aspects of methyl bromide toxicity. Few studies have performed a detailed exposure assessment including biomonitoring. Three evaluated epidemiological studies assessed a possible association between cancer and methyl bromide. Overall, exposure to methyl bromide is associated with an increased risk of prostate cancer OR, 1.21; 95% CI (0,98-1.49), P = 0.076. Two epidemiological studies have analyzed environmental, non-occupational exposure to methyl bromide providing evidence for its health risk to the general public. None of the epidemiological studies addressed its use as a fumigant in freight containers, although recent field and case reports do refer to its toxic effects associated with its use in shipping and storage.
Conclusions:
Both the epidemiological evidence and toxicological data suggest a possible link between methyl bromide exposure and serious health problems, including prostate cancer risk from occupational and community exposure. The environmental risks of methyl bromide are not in doubt, but also its health risks, especially for genetically predisposed subjects, should not be underestimated.
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An ecological quantification of the relationships between water, sanitation and infant, child, and maternal mortality
Background:
Water and sanitation access are known to be related to newborn, child, and maternal health. Our study attempts to quantify these relationships globally using country-level data: How much does improving access to water and sanitation influence infant, child, and maternal mortality?
Methods:
Data for 193 countries were abstracted from global databases (World Bank, WHO, and UNICEF). Linear regression was used for the outcomes of under-five mortality rate and infant mortality rate (IMR). These results are presented as events per 1000 live births. Ordinal logistic regression was used to compute odds ratios for the outcome of maternal mortality ratio (MMR).
Results:
Under-five mortality rate decreased by 1.17 (95%CI 1.08-1.26) deaths per 1000, p < 0.001, for every quartile increase in population water access after adjustments for confounders. There was a similar relationship between quartile increase of sanitation access and under-five mortality rate, with a decrease of 1.66 (95%CI 1.11-1.32) deaths per 1000, p < 0.001. Improved water access was also related to IMR, with the IMR decreasing by 1.14 (95%CI 1.05-1.23) deaths per 1000, p < 0.001, with increasing quartile of access to improved water source. The significance of this relationship was retained with quartile improvement in sanitation access, where the decrease in IMR was 1.66 (95%CI 1.11-1.32) deaths per 1000, p < 0.001. The estimated odds ratio that increased quartile of water access was significantly associated with increased quartile of MMR was 0.58 (95%CI 0.39-0.86), p = 0.008. The corresponding odds ratio for sanitation was 0.52 (95%CI 0.32-0.85), p = 0.009, both suggesting that better water and sanitation were associated with decreased MMR.
Conclusions:
Our analyses suggest that access to water and sanitation independently contribute to child and maternal mortality outcomes. If the world is to seriously address the Millennium Development Goals of reducing child and maternal mortality, then improved water and sanitation accesses are key strategies.
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Emergency department visits, ambulance calls, and mortality associated with an exceptional heat wave in Sydney, Australia, 2011: a time-series analysis
Background:
From January 30-February 6, 2011, New South Wales was affected by an exceptional heat wave, which broke numerous records. Near real-time Emergency Department (ED) and ambulance surveillance allowed rapid detection of an increase in the number of heat-related ED visits and ambulance calls during this period. The purpose of this study was to quantify the excess heat-related and all-cause ED visits and ambulance calls, and excess all-cause mortality, associated with the heat wave.
Methods:
ED and ambulance data were obtained from surveillance and administrative databases, while mortality data were obtained from the state death registry. The observed counts were compared with the average counts from the same period from 2006/07 through 2009/10, and a Poisson regression model was constructed to calculate the number of excess ED visits, ambulance calls and deaths after adjusting for calendar and lag effects.
Results:
During the heat wave there were 104 and 236 ED visits for heat effects and dehydration respectively, and 116 ambulance calls for heat exposure. From the regression model, all-cause ED visits increased by 2% (95% CI 1.01-1.03), all-cause ambulance calls increased by 14% (95% CI 1.11-1.16), and all-cause mortality increased by 13% (95% CI 1.06-1.22). Those aged 75 years and older had the highest excess rates of all outcomes.
Conclusions:
The 2011 heat wave resulted in an increase in the number of ED visits and ambulance calls, especially in older persons, as well as an increase in all-cause mortality. Rapid surveillance systems provide markers of heat wave impacts that have fatal outcomes.
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Occurrence of mental illness following prenatal and early childhood exposure to tetrachloroethylene (PCE)-contaminated drinking water: a retrospective cohort study
Background:
While many studies of adults with solvent exposure have shown increased risks of anxiety and depressive disorders, there is little information on the impact of prenatal and early childhood exposure on the subsequent risk of mental illness. This retrospective cohort study examined whether early life exposure to tetrachloroethylene (PCE)-contaminated drinking water influenced the occurrence of depression, bipolar disorder, post-traumatic stress disorder, and schizophrenia among adults from Cape Cod, Massachusetts.
Methods:
A total of 1,512 subjects born between 1969 and 1983 were studied, including 831 subjects with both prenatal and early childhood PCE exposure and 547 unexposed subjects. Participants completed questionnaires to gather information on mental illnesses, demographic and medical characteristics, other sources of solvent exposure, and residences from birth through 1990. PCE exposure originating from the vinyl-liner of water distribution pipes was assessed using water distribution system modeling software that incorporated a leaching and transport algorithm.
Results:
No meaningful increases in risk ratios (RR) for depression were observed among subjects with prenatal and early childhood exposure (RR: 1.1, 95% CI: 0.9-1.4). However, subjects with prenatal and early childhood exposure had a 1.8-fold increased risk of bipolar disorder (N=36 exposed cases, 95% CI: 0.9-1.4), a 1.5-fold increased risk post-traumatic stress disorder (N=47 exposed cases, 95% CI: 0.9-2.5), and a 2.1-fold increased risk of schizophrenia (N=3 exposed cases, 95% CI: 0.2-20.0). Further increases in the risk ratio were observed for bipolar disorder (N=18 exposed cases, RR; 2.7, 95% CI: 1.3-5.6) and post-traumatic stress disorder (N=18 exposed cases, RR: 1.7, 95% CI: 0.9-3.2) among subjects with the highest exposure levels.
Conclusions:
The results of this study provide evidence against an impact of early life exposure to PCE on the risk of depression. In contrast, the results provide support for an impact of early life exposure on the risk of bipolar disorder and post-traumatic stress disorder. The number of schizophrenia cases was too small to draw reliable conclusions. These findings should be confirmed in investigations of other similarly exposed populations.
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Households' Perception of Climate Change and Human Health Risks: A community perspective
Background:
Bangladesh has been identified as one of the most vulnerable countries in the world concerning the adverse effects of climate change (CC). However, little is known about the perception of CC from the community, which is important for developing adaptation strategies.
Methods:
The study was a cross-sectional survey of respondents from two villages--one from the northern part and the other from the southern part of Bangladesh. A total of 450 households were selected randomly through multistage sampling completed a semi-structure questionnaire. This was supplemented with 12 focus group discussions (FGDs) and 15 key informant interviews (KIIs).
Results:
Over 95 percent of the respondents reported that the heat during the summers had increased and 80.2 percent reported that rainfall had decreased, compared to their previous experiences. Approximately 65 percent reported that winters were warmer than in previous years but they still experienced very erratic and severe cold during the winter for about 5-7 days, which restricted their activities with very destructive effect on agricultural production, everyday life and the health of people. FGDs and KIIs also reported that overall winters were warmer. Eighty point two percent, 72.5 percent and 54.7 percent survey respondents perceived that the frequency of water, heat and cold related diseases/health problems, respectively, had increased compared to five to ten years ago. FGDs and KIIs respondents were also reported the same.
Conclusions:
Respondents had clear perceptions about changes in heat, cold and rainfall that had occurred over the last five to ten years. Local perceptions of climate variability (CV) included increased heat, overall warmer winters, reduced rainfall and fewer floods. The effects of CV were mostly negative in terms of means of living, human health, agriculture and overall livelihoods. Most local perceptions on CV are consistent with the evidence regarding the vulnerability of Bangladesh to CC. Such findings can be used to formulate appropriate sector programs and interventions. The systematic collection of such information will allow scientists, researchers and policy makers to design and implement appropriate adaptation strategies for CC in countries that are especially vulnerable.
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Impact of tubewell access and tubewell depth on childhood diarrhea in Matlab, Bangladesh
Background:
During the past three decades in Bangladesh, millions of tubewells have been installed to reduce the prevalence of diarrheal disease. This study evaluates the impacts of tubewell access and tubewell depth on childhood diarrhea in rural Bangladesh.
Methods:
A total of 59,796 cases of diarrhea in children under 5 were recorded in 142 villages of Matlab, Bangladesh during monthly community health surveys between 2000 and 2006. The location and depth of 12,018 tubewells were surveyed in 2002-04 and integrated with diarrhea and other data in a geographic information system. A proxy for tubewell access was developed by calculating the local density of tubewells around households. Logistic regression models were built to examine the relationship between childhood diarrhea, tubewell density and tubewell depth. Wealth, adult female education, flood control, population density and the child's age were considered as potential confounders.
Results:
Baris (patrilineally-related clusters of households) with greater tubewell density were associated with significantly less diarrhea (OR (odds ratio)=0.87, 95% confidence interval (CI): 0.85-0.89). Tubewell density had a greater influence on childhood diarrhea in areas that were not protected from flooding. Baris using intermediate depth tubewells (140-300 feet) were associated with more childhood diarrhea (OR=1.24, 95% CI: 1.19-1.29) than those using shallow wells (10-140 feet). Baris using deep wells (300-990 feet) had less diarrheal disease than those using shallow wells, however, the difference was significant only when population density was low (<1000 person/km2) or children were at the age of 13-24 months.
Conclusions:
Increased access to tubewells is associated with a lower risk of childhood diarrhea. Intermediate- depth wells are associated with more childhood diarrhea compared to shallower or deeper wells. These findings may have implications for on-going efforts to reduce exposure to elevated levels of arsenic contained in groundwater that is pumped in this study area primarily from shallow tubewells.
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Effects of Particulate Air Pollution on Blood Pressure in a Highly Exposed Population in Beijing, China: A repeated-measure study
Background:
Particulate Matter (PM) exposure is critical in Beijing due to high population density and rapid increase in vehicular traffic. PM effects on blood pressure (BP) have been investigated as a mechanism mediating cardiovascular risks, but results are still inconsistent. The purpose of our study is to determine the effects of ambient and personal PM exposure on BP.
Methods:
Before the 2008 Olympic Games (June 15-July 27), we examined 60 truck drivers and 60 office workers on two days, 1-2 weeks apart (n=240). We obtained standardized measures of post-work BP. Exposure assessment included personal PM2.5 and Elemental Carbon (EC, a tracer of traffic particles) measured using portable monitors during work hours; and ambient PM10 averaged over 1-8 days pre-examination. We examined associations of exposures (exposure group, personal PM2.5/EC, ambient PM10) with BP controlling for multiple covariates.
Results:
Mean personal PM2.5 was 94.6 ug/m3 (SD=64.9) in office workers and 126.8 (SD=68.8) in truck drivers (p-value<0.001). In all participants combined, a 10 mug/m3 increase in 8-day ambient PM10 was associated with BP increments of 0.98 (95%CI 0.34; 1.61; p-value=0.003), 0.71 (95%CI 0.18; 1.24; p-value=0.01), and 0.81 (95%CI 0.31; 1.30; p-value=0.002) mmHg for systolic, diastolic, and mean BP, respectively. BP was not significantly different between the two groups (p-value>0.14). Personal PM2.5 and EC during work hours were not associated with increased BP.
Conclusions:
Our results indicate delayed effects of ambient PM10 on BP. Lack of associations with exposure groups and personal PM2.5/EC indicates that PM effects are related to background levels of pollution in Beijing, and not specifically to work-related exposure.
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Data sharing: not as simple as it seems
In recent years there has been a major change on the part of funders, particularly in North America, so that data sharing is now considered to be the norm rather than the exception. We believe that data sharing is a good idea. However, we also believe that it is inappropriate to prescribe exactly when or how researchers should preserve and share data, since these issues are highly specific to each study, the nature of the data collected, who is requesting it, and what they intend to do with it. The level of ethical concern will vary according to the nature of the information, and the way in which it is collected - analyses of anonymised hospital admission records may carry a quite different ethical burden than analyses of potentially identifiable health information collected directly from the study participants. It is striking that most discussions about data sharing focus almost exclusively on issues of ownership (by the researchers or the funders) and efficiency (on the part of the funders). There is usually little discussion of the ethical issues involved in data sharing, and its implications for the study participants. Obtaining prior informed consent from the participants does not solve this problem, unless the informed consent process makes it completely clear what is being proposed, in which case most study participants would not agree. Thus, the undoubted benefits of data sharing does not remove the obligations and responsibilities that the original investigators hold for the people they invited to participate in the study.
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Childhood brain tumour risk and its association with wireless phones: a commentary
Case-control studies on adults point to an increased risk of brain tumours (glioma and acoustic neuroma) associated with the long-term use of mobile phones. Recently, the first study on mobile phone use and the risk of brain tumours in children and adolescents, CEFALO, was published. It has been claimed that this relatively small study yielded reassuring results of no increased risk. We do not agree. We consider that the data contain several indications of increased risk, despite low exposure, short latency period, and limitations in the study design, analyses and interpretation. The information certainly cannot be used as reassuring evidence against an association, for reasons that we discuss in this commentary.
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Relation between dietary cadmium intake and biomarkers of cadmium exposure in premenopausal women accounting for body iron stores
Background:
Cadmium is a widespread environmental pollutant with adverse effects on kidneys and bone, but with insufficiently elucidated public health consequences such as risk of end-stage renal diseases, fractures and cancer. Urinary cadmium is considered a valid biomarker of lifetime kidney accumulation from overall cadmium exposure and thus used in the assessment of cadmium-induced health effects. We aimed to assess the relationship between dietary cadmium intake assessed by analyses of duplicate food portions and cadmium concentrations in urine and blood, taking the toxicokinetics of cadmium into consideration.
Methods:
In a sample of 57 non-smoking Swedish women aged 20-50 years, we assessed Pearson's correlation coefficients between: 1) Dietary intake of cadmium assessed by analyses of cadmium in duplicate food portions collected during four consecutive days and cadmium concentrations in urine, 2) Partial correlations between the duplicate food portions and urinary and blood cadmium concentrations, respectively, and 3) Model-predicted urinary cadmium concentration predicted from the dietary intake using a one-compartment toxicokinetic model (with individual data on age, weight and gastrointestinal cadmium absorption) and urinary cadmium concentration.
Results:
The mean concentration of cadmium in urine was 0.18 (+/- s.d.0.12) μg/g creatinine and the model-predicted urinary cadmium concentration was 0.19 (+/- s.d.0.15) μg/g creatinine. The partial Pearson correlations between analyzed dietary cadmium intake and urinary cadmium or blood concentrations were r = 0.43 and 0.42, respectively. The correlation between diet and urinary cadmium increased to r = 0.54 when using a one-compartment model with individual gastrointestinal cadmium absorption coefficients based on the women's iron status.
Conclusions:
Our results indicate that measured dietary cadmium intake can reasonably well predict biomarkers of both long-term kidney accumulation (urine) and short-term exposure (blood). The predictions are improved when taking data on the iron status into account.
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Epidemiologic Perspectives & Innovations - Latest Articles
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Social network analysis and agent-based modeling in social epidemiology
The past five years have seen a growth in the interest in systems approaches in epidemiologic research. These approaches may be particularly appropriate for social epidemiology. Social network analysis and agent-based models (ABMs) are two approaches that have been used in the epidemiologic literature. Social network analysis involves the characterization of social networks to yield inference about how network structures may influence risk exposures among those in the network. ABMs can promote population-level inference from explicitly programmed, micro-level rules in simulated populations over time and space. In this paper, we discuss the implementation of these models in social epidemiologic research, highlighting the strengths and weaknesses of each approach. Network analysis may be ideal for understanding social contagion, as well as the influences of social interaction on population health. However, network analysis requires network data, which may sacrifice generalizability, and causal inference from current network analytic methods is limited. ABMs are uniquely suited for the assessment of health determinants at multiple levels of influence that may couple with social interaction to produce population health. ABMs allow for the exploration of feedback and reciprocity between exposures and outcomes in the etiology of complex diseases. They may also provide the opportunity for counterfactual simulation. However, appropriate implementation of ABMs requires a balance between mechanistic rigor and model parsimony, and the precision of output from complex models is limited. Social network and agent-based approaches are promising in social epidemiology, but continued development of each approach is needed.
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The use of complete-case and multiple imputation-based analyses in molecular epidemiology studies that assess interaction effects
Background:
In molecular epidemiology studies biospecimen data are collected, often with the purpose of evaluating the synergistic role between a biomarker and another feature on an outcome. Typically, biomarker data are collected on only a proportion of subjects eligible for study, leading to a missing data problem. Missing data methods, however, are not customarily incorporated into analyses. Instead, complete-case (CC) analyses are performed, which can result in biased and inefficient estimates.
Methods:
Through simulations, we characterized the performance of CC methods when interaction effects are estimated. We also investigated whether standard multiple imputation (MI) could improve estimation over CC methods when the data are not missing at random (NMAR) and auxiliary information may or may not exist.
Results:
CC analyses were shown to result in considerable bias and efficiency loss. While MI reduced bias and increased efficiency over CC methods under specific conditions, it too resulted in biased estimates depending on the strength of the auxiliary data available and the nature of the missingness. In particular, CC performed better than MI when extreme values of the covariate were more likely to be missing, while MI outperformed CC when missingness of the covariate related to both the covariate and outcome. MI always improved performance when strong auxiliary data were available. In a real study, MI estimates of interaction effects were attenuated relative to those from a CC approach.
Conclusions:
Our findings suggest the importance of incorporating missing data methods into the analysis. If the data are MAR, standard MI is a reasonable method. Auxiliary variables may make this assumption more reasonable even if the data are NMAR. Under NMAR we emphasize caution when using standard MI and recommend it over CC only when strong auxiliary data are available. MI, with the missing data mechanism specified, is an alternative when the data are NMAR. In all cases, it is recommended to take advantage of MI's ability to account for the uncertainty of these assumptions.
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Attributing the burden of cancer at work: three areas of concern when examining the example of shift-work
This commentary intends to instigate discussions about epidemiologic estimates and their interpretation of attributable fractions (AFs) and the burden of disease (BOD) of cancers due to factors at workplaces. By examining recent work that aims to estimate the number of cancers attributable to shift-work in Britain, we suggest that (i) causal, (ii) practical and (iii) methodological areas of concern may deter us from attributable caseload estimations of cancers at this point in time. Regarding (i), such calculations may have to be avoided as long as we lack established causality between shift-work and the development of internal cancers. Regarding (ii), such calculations may have to be avoided as long as we can neither abandon shift-work nor identify personnel that may be unaffected by shift-work factors. Regarding (iii), there are at least four methodological pitfalls which are likely to make AF calculations uninterpretable at this stage. The four pitfalls are: (1) The use of Levin's 1953 formula in case of adjusted relative risks; (2) The use of broad definitions of exposure in calculations of AFs; (3) The non-additivity of AFs across different levels of exposure and covariables; (4) The fact that excess mortality counts are misleading due to the fact that a human being dies exactly once - a death may occur earlier or later, but a death cannot occur more than once nor can it be avoided altogether for any given individual. Overall, causal, practical and methodological areas of concern should be diligently considered when performing and interpreting AF or BOD computations which - at least at the present time - may not be defensible.
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Clustering Based on Adherence Data
Adherence to a medical treatment means the extent to which a patient follows the instructions or recommendations by health professionals. There are direct and indirect ways to measure adherence which have been used for clinical management and research. Typically adherence measures are monitored over a long follow-up or treatment period, and some measurements may be missing due to death or other reasons. A natural question then is how to describe adherence behavior over the whole period in a simple way. In the literature, measurements over a period are usually combined just by using averages like percentages of compliant days or percentages of doses taken. In the paper we adapt an approach where patient adherence measures are seen as a stochastic process. Repeated measures are then analyzed as a Markov chain with finite number of states rather than as independent and identically distributed observations, and the transition probabilities between the states are assumed to fully describe the behavior of a patient. The patients can then be clustered or classified using their estimated transition probabilities. These natural clusters can be used to describe the adherence of the patients, to find predictors for adherence, and to predict the future events. The new approach is illustrated and shown to be useful with a simple analysis of a data set from the DART (Development of AntiRetroviral Therapy in Africa) trial in Uganda and Zimbabwe.
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Disease-specific prospective family study cohorts enriched for familial risk
Most common diseases demonstrate familial aggregation; the ratio of the risk for relatives of affected people to the risk for relatives of unaffected people (the familial risk ratio)) > 1. This implies there are underlying genetic and/or environmental risk factors shared by relatives. The risk gradient across this underlying 'familial risk profile', which can be predicted from family history and measured familial risk factors, is typically strong. Under a multiplicative model, the ratio of the risk for people in the upper 25% of familial risk to the risk for those in the lower 25% (the inter-quartile risk gradient) is an order of magnitude greater than the familial risk ratio. If familial risk ratio = 2 for first-degree relatives, in terms of familial risk profile: (a) people in the upper quartile will be at more than 20 times the risk of those in the lower quartile; and (b) about 90% of disease will occur in people above the median. Historically, therefore, epidemiology has compared cases with controls dissimilar for underlying familial risk profile. Were gene-environment and gene-gene interactions to exist, environmental and genetic effects could be stronger for people with increased familial risk profile. Studies in which controls are better matched to cases for familial risk profile might be more informative, especially if both cases and controls are over-sampled for increased familial risk. Prospective family study cohort (ProF-SC) designs involving people across a range of familial risk profile provide such a resource for epidemiological, genetic, behavioural, psycho-social and health utilisation research. The prospective aspect gives credibility to risk estimates. The familial aspect allows family-based designs, matching for unmeasured factors, adjusting for underlying familial risk profile, and enhanced cohort maintenance.
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WINPEPI updated: computer programs for epidemiologists, and their teaching potential
Background:
The WINPEPI computer programs for epidemiologists are designed for use in practice and research in the health field and as learning or teaching aids. The programs are free, and can be downloaded from the Internet. Numerous additions have been made in recent years.ImplementationThere are now seven WINPEPI programs: DESCRIBE, for use in descriptive epidemiology; COMPARE2, for use in comparisons of two independent groups or samples; PAIRSetc, for use in comparisons of paired and other matched observations; LOGISTIC, for logistic regression analysis; POISSON, for Poisson regression analysis; WHATIS, a "ready reckoner" utility program; and ETCETERA, for miscellaneous other procedures. The programs now contain 122 modules, each of which provides a number, sometimes a large number, of statistical procedures. The programs are accompanied by a Finder that indicates which modules are appropriate for different purposes. The manuals explain the uses, limitations and applicability of the procedures, and furnish formulae and references.
Conclusions:
WINPEPI is a handy resource for a wide variety of statistical routines used by epidemiologists. Because of its ready availability, portability, ease of use, and versatility, WINPEPI has a considerable potential as a learning and teaching aid, both with respect to practical procedures in the planning and analysis of epidemiological studies, and with respect to important epidemiological concepts. It can also be used as an aid in the teaching of general basic statistics.
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Reporting errors in infectious disease outbreaks, with an application to Pandemic Influenza A/H1N1
Background:
Effectively responding to infectious disease outbreaks requires a well-informed response. Quantitative methods for analyzing outbreak data and estimating key parameters to characterize the spread of the outbreak, including the reproductive number and the serial interval, often assume that the data collected is complete. In reality reporting delays, undetected cases or lack of sensitive and specific tests to diagnose disease lead to reporting errors in the case counts. Here we provide insight on the impact that such reporting errors might have on the estimation of these key parameters.
Results:
We show that when the proportion of cases reported is changing through the study period, the estimates of key epidemiological parameters are biased. Using data from the Influenza A/H1N1 outbreak in La Gloria, Mexico, we provide estimates of these parameters, accounting for possible reporting errors, and show that they can be biased by as much as 33%, if reporting issues are not accounted for.
Conclusions:
Failure to account for missing data can lead to misleading and inaccurate estimates of epidemic parameters.
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Shift work, cancer and "white-box" epidemiology:
Association and causation
This commentary intends to instigate discussions about upcoming epidemiologic research, and its interpretation, into putative links between shift work, involving circadian disruption or chronodisruption [CD], and the development of internal cancers.In 2007, the International Agency for Research on Cancer (IARC) convened an expert group to examine the carcinogenicity of shift work, inter alia characterized by light exposures at unusual times. After a critical review of published data, the following was stated: "There is sufficient evidence in experimental animals for the carcinogenicity of light during the daily dark period (biological night)". However, in view of limited epidemiological evidence, it was overall concluded: "Shiftwork that involves circadian disruption is probably carcinogenic to humans (Group 2A)".Remarkably, the scenario around shift work, CD and internal cancers provides a unique case for "white-box" epidemiology: Research at many levels - from sub-cellular biochemistry, to whole cells, to organs, to organisms, including animals and humans - has suggested a series of quite precise and partly related causal mechanisms. This is in stark contrast to instances of "black box" or "stabs in the dark" epidemiology where causal mechanisms are neither known nor hypothesized or only poorly defined. The overriding theme that an adequate chronobiological organization of physiology can be critical for the protection against cancer builds the cornerstone of biological plausibility in this case.We can now benefit from biological plausibility in two ways: First, epidemiology should use biologically plausible insights into putative chains of causation between shift work and cancer to design future investigations. Second, when significant new data were to become available in coming years, IARC will re-evaluate cancer hazards associated with shift work. Biological plausibility may then be a key viewpoint to consider and, ultimately, to decide whether (or not) to pass from statistical associations, possibly detected in observational studies by then, to a verdict of causation.In the meantime, biological plausibility should not be invoked to facilitate publication of epidemiological research of inappropriate quality. Specific recommendations as to how to design, report and interpret epidemiological research into biologically plausible links between shift work and cancer are provided.Epidemiology is certainly a poor toolfor learning about the mechanismby which a disease is produced,but it has the tremendous advantagethat it focuses on the diseases and the deathsthat actually occur,and experience has shown that it continues to be second to none asa means of discovering linksin the chain of causationthat are capable of being broken.-Sir Richard Doll
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Carcinogen metabolism, cigarette smoking, and breast cancer risk: A Bayes Model Averaging approach
Background:
Standard logistic regression with or without stepwise selection has the disadvantage of not incorporating model uncertainty and the dependency of estimates on the underlying model into the final inference. We explore the use of a Bayes Model Averaging approach as an alternative to analyze the influence of genetic variants, environmental effects and their interactions on disease.
Methods:
Logistic regression with and without stepwise selection and Bayes Model Averaging were applied to a population-based case-control study exploring the association of genetic variants in tobacco smoke-related carcinogen pathways with breast cancer.
Results:
Both regression and Bayes Model Averaging highlighted a significant effect of NAT1*10 on breast cancer, while regression analysis also suggested a significant effect for packyears and for the interaction of packyears and NAT2.
Conclusions:
Bayes Model Averaging allows incorporation of model uncertainty, helps reduce dimensionality and avoids the problem of multiple comparisons. It can be used to incorporate biological information, such as pathway data, into the analysis. As with all Bayesian analysis methods, careful consideration must be given to prior specification.
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Categorisation of continuous risk factors in epidemiological publications: a survey of current practice
Background:
Reports of observational epidemiological studies often categorise (group) continuous risk factor (exposure) variables. However, there has been little systematic assessment of how categorisation is practiced or reported in the literature and no extended guidelines for the practice have been identified. Thus, we assessed the nature of such practice in the epidemiological literature. Two months (December 2007 and January 2008) of five epidemiological and five general medical journals were reviewed. All articles that examined the relationship between continuous risk factors and health outcomes were surveyed using a standard proforma, with the focus on the primary risk factor. Using the survey results we provide illustrative examples and, combined with ideas from the broader literature and from experience, we offer guidelines for good practice.
Results:
Of the 254 articles reviewed, 58 were included in our survey. Categorisation occurred in 50 (86%) of them. Of those, 42% also analysed the variable continuously and 24% considered alternative groupings. Most (78%) used 3 to 5 groups. No articles relied solely on dichotomisation, although it did feature prominently in 3 articles. The choice of group boundaries varied: 34% used quantiles, 18% equally spaced categories, 12% external criteria, 34% other approaches and 2% did not describe the approach used. Categorical risk estimates were most commonly (66%) presented as pairwise comparisons to a reference group, usually the highest or lowest (79%). Reporting of categorical analysis was mostly in tables; only 20% in figures.
Conclusions:
Categorical analyses of continuous risk factors are common. Accordingly, we provide recommendations for good practice. Key issues include pre-defining appropriate choice of groupings and analysis strategies, clear presentation of grouped findings in tables and figures, and drawing valid conclusions from categorical analyses, avoiding injudicious use of multiple alternative analyses.
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Frontiers in Zoology - Latest Articles
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Landscape requirements of a primate population in a human-dominated environment
IntroductionAs urban and rural land development become widespread features of the global landscape so an understanding of the landscape requirements of displaced and isolated wildlife species becomes increasingly important for conservation planning. In the Cape Peninsula, South Africa, rapid human population growth, and the associated urban and rural land transformation, threatens the sustainability of the local chacma baboon population. Here we analyse spatial data collected from nine of the 12 extant troops to determine their population-level landscape requirements. We use hurdle models to ascertain the key landscape features influencing baboon occurrence and abundance patterns on two hierarchical spatial scales.
Results:
Both spatial scales produced similar results that were ecologically reliable and interpretable. The models indicated that baboons were more likely to occur, and be more abundant, at low altitudes, on steep slopes and in human-modified habitats. The combination of these landscape variables provides baboons with access to the best quality natural and anthropogenic food sources in close proximity to one another and suitable sleeping sites. Surface water did not emerge as an influential landscape feature presumably as the area is not water stressed.
Conclusions:
The model results indicate that land development in the Cape Peninsula has pushed baboons into increasingly marginal natural habitat while simultaneously providing them with predictable and easily accessible food sources in human-modified habitats. The resultant spatial competition between humans and baboons explains the high levels of human-baboon conflict and further erosion of the remaining land fragments is predicted to exacerbate competition. This study demonstrates how the quantification of animal landscape requirements can provide a mechanism for identifying priority conservation areas at the human-wildlife interface.
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An Intermediate in the evolution of superfast sonic muscles
Abstract
Background:
Intermediate forms in the evolution of new adaptations such as transitions from water to land and the evolution of flight are often poorly understood. Similarly, the evolution of superfast sonic muscles in fishes, often considered the fastest muscles in vertebrates, has been a mystery because slow bladder movement does not generate sound. Slow muscles that stretch the swimbladder and then produce sound during recoil have recently been discovered in ophidiiform fishes. Here we describe the disturbance call (produced when fish are held) and sonic mechanism in an unrelated perciform pearl perch (Glaucosomatidae) that represents an intermediate condition in the evolution of super-fast sonic muscles.
Results:
The pearl perch disturbance call is a two-part sound produced by a fast sonic muscle that rapidly stretches the bladder and an antagonistic tendon-smooth muscle combination (part 1) causing the tendon and bladder to snap back (part 2) generating a higher-frequency and greater-amplitude pulse. The smooth muscle is confirmed by electron microscopy and protein analysis. To our knowledge smooth muscle attachment to a tendon is unknown in animals.
Conclusion:
The pearl perch, an advanced perciform teleost unrelated to ophidiiform fishes, uses a slow type mechanism to produce the major portion of the sound pulse during recoil, but the swimbladder is stretched by a fast muscle. Similarities between the two unrelated lineages, suggest independent and convergent evolution of sonic muscles and indicate intermediate forms in the evolution of superfast muscles.
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Control of social monogamy through aggression in a hermaphroditic shrimp
IntroductionSex allocation theory predicts that in small mating groups simultaneous hermaphroditism is the optimal form of gender expression. Under these conditions, male allocation is predicted to be very low and overall per-capita reproductive output maximal. This is particularly true for individuals that live in pairs, but monogamy is highly susceptible to cheating by both partners. However, certain conditions favour social monogamy in hermaphrodites. This study addresses the influence of group size on group stability and moulting cycles in singles, pairs, triplets and quartets of the socially monogamous shrimp Lysmata amboinensis, a protandric simultaneous hermaphrodite.
Results:
The effect of group size was very strong: Exactly one individual in each triplet and exactly two individuals in each quartet were killed in aggressive interactions, resulting in group sizes of two individuals. All killed individuals had just moulted. No mortality occurred in single and pair treatments. The number of moults in the surviving shrimp increased significantly after changing from triplets and quartets to pairs.
Conclusion:
Social monogamy in L. amboinensis is reinforced by aggressive expulsion of supernumerous individuals. We suggest that the high risk of mortality in triplets and quartets results in suppression of moulting in groups larger than two individuals and that the feeding ecology of L. amboinensis favours social monogamy.
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Does age matter in song bird vocal interactions? Results from interactive playback experiments.
The song of oscines provides an extensively studied model of age-dependent behaviour changes. Male and female receivers might use song characteristics to obtain information about the age of a signaller, which is often related to its quality. Whereas most of the age-dependent song changes have been studied in solo singing, the role of age in vocal interactions is less well understood. We addressed this issue in a playback study with common nightingales (Luscinia megarhynchos). Previous studies showed that male nightingales had smaller repertoires in their first year than older males and males adjusted their repertoire towards the most common songs in the breeding population. We now compared vocal interaction patterns in a playback study in 12 one year old and 12 older nightingales (cross-sectional approach). Five of these males were tested both in their first and second breeding season (longitudinal approach). Song duration and latency to respond did not differ between males of different ages in either approach. In the cross-sectional approach, one year old nightingales matched song types twice as often as did older birds. Similarly, in the longitudinal approach all except one bird reduced the number of song type matches in their second season. Individuals tended to overlap songs at higher rates in their second breeding season than in their first. The higher levels of song type matches in the first year and song overlapping by birds in their second year suggest that these are communicative strategies to establish relationships with competing males and/or choosy females.
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Prior contest experience exerts a long-term influence on subsequent winner and loser effects
IntroductionAnimals are capable of using information from recent experiences to modify subsequent behavioral responses. Animals' ability or propensity to modify their behavior in the light of new information has repeatedly been shown to correlate with, or be influenced by, either their intrinsic competitive ability or their dominance experience - an influence which can be long-lasting. Using a mangrove killifish, Kryptolebias marmoratus, as the study organism, we investigated whether and if so how the effect of a winning or a losing experience one day prior to a dyadic contest was modulated by both competitive ability measured two months previously and a winning or losing experience forced on the contestants one month previously.
Results:
Winning/losing experience forced on the fish one month previously affected how they utilized information from their winning/losing experience one day before Test Day: Individuals that were randomly assigned a losing experience one month previously were more susceptible to the influence of their 1-day winning/losing experience than those assigned a winning experience. Competitive ability measured two months previously, winning/losing experience from one month previously and the winning/losing experience received one day previously all significantly influenced the fish's contest behaviors on Test Day, although only 2-month competitive ability significantly influenced escalation duration, indicating that it was still a good index for the fish's competitive ability two months later.
Conclusions:
These results suggest that the value to the fish of information from a recent win or loss depends on the outcome of their past contests and show that contest experience has a long-term effect on contest behavior.
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Easier detection of invertebrate "identification-key characters" with light of different wavelengths
The marine α-taxonomist often encounters two problems. Firstly, the "environmental dirt" that is frequently present on the specimens and secondly the difficulty in distinguishing key-features due to the uniform colours which fixed animals often adopt.Here we show that illuminating animals with deep-blue or ultraviolet light instead of the normal white-light abrogates both difficulties; dirt disappears and important details become clearly visible. This light regime has also two other advantages. It allows easy detection of very small, normally invisible, animals (0.1 μm range). And as these light wavelengths can induce fluorescence, new identification markers may be discovered by this approach.
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Prevalence of blood parasites in seabirds- a review
IntroductionWhile blood parasites are common in many birds in the wild, some groups seem to be much less affected. Seabirds, in particular, have often been reported free from blood parasites, even in the presence of potential vectors.
Results:
From a literature review of hemosporidian prevalence in seabirds, we collated a dataset of 60 species, in which at least 15 individuals had been examined. These data were included in phylogenetically controlled statistical analyses of hemosporidian prevalence in relation to ecological and life-history parameters. Haemoproteus parasites were common in frigatebirds and gulls, while Hepatozoon occurred in albatrosses and storm petrels, and Plasmodium mainly in penguins. The prevalence of Haemoproteus showed a geographical signal, being lower in species with distribution towards polar environments. Interspecific differences in Plasmodium prevalence were explained by variables that relate to the exposure to parasites, suggesting that prevalence is higher in burrow nesters with long fledgling periods. Measures of Plasmodium, but not Haemoproteus prevalences were influenced by the method, with PCR-based data resulting in higher prevalence estimates.
Conclusions:
Our analyses suggest that, as in other avian taxa, phylogenetic, ecological and life-history parameters determine the prevalence of hemosporidian parasites in seabirds. We discuss how these relationships should be further explored in future studies.
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The taxonomist - an endangered race. A practical proposal for its survival
Background:
Taxonomy or biological systematics is the basic scientific discipline of biology, postulating hypotheses of identity and relationships, on which all other natural sciences dealing with organisms relies. However, the scientific contributions of taxonomists have been largely neglected when using species names in scientific publications by not citing the authority on which they are based.DiscussionConsequences of this neglect is reduced recognition of the importance of taxonomy, which in turn results in diminished funding, lower interest from journals in publishing taxonomic research, and a reduced number of young scientists entering the field. This has lead to the so-called taxonomic impediment at a time when biodiversity studies are of critical importance.Here we emphasize a practical and obvious solution to this dilemma. We propose that whenever a species name is used, the author(s) of the species hypothesis be included and the original literature source cited, including taxonomic revisions and identification literature - nothing more than what is done for every other hypothesis or assumption included in a scientific publication. In addition, we postulate that journals primarily publishing taxonomic studies should be indexed in ISISM.SummaryThe proposal outlined above would make visible the true contribution of taxonomists within the scientific community, and would provide a more accurate assessment for funding agencies impact and importance of taxonomy, and help in the recruitment of young scientists into the field, thus helping to alleviate the taxonomic impediment. In addition, it would also make much of the biological literature more robust by reducing or alleviating taxonomic uncertainty.
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Maternal effects mediated by egg quality in the Yellow-legged Gull Larus michahellis in relation to laying order and embryo sex
Background:
Maternal effects mediated by egg size and quality may profoundly affect offspring development and performance, and mothers may adjust egg traits according to environmental or social influences. In avian species, context-dependency of maternal effects may result in variation in egg composition, as well as in differential patterns of covariation among selected egg components, according to, for example, position in the laying sequence or offspring sex. We investigated variation in major classes of egg yolk components (carotenoids, vitamins and steroid hormones) in relation to egg size, position in the laying sequence and embryo sex in clutches of the Yellow-legged Gull (Larus michahellis). We also investigated their covariation, to highlight mutual adjustments, maternal constraints or trade-offs in egg allocation.
Results:
Laying sequence-specific patterns of allocation emerged: concentration of carotenoids and vitamin E decreased, while concentrations of androgens increased. Vitamin A, estradiol and corticosterone did not show any change. There was no evidence of sex-specific allocation or covariation of yolk components. Concentrations of carotenoids and vitamins were positively correlated. Egg mass decreased along the laying sequence, and this decrease was negatively correlated with the mean concentrations of carotenoids in clutches, suggesting that nutritionally constrained females lay low quality clutches in terms of carotenoid content. Finally, clutches with smaller decline in antioxidants between first- and last-laid eggs had a larger increase in yolk corticosterone, suggesting that a smaller antioxidant depletion along the laying sequence may entail a cost for laying females in terms of increased stress levels.
Conclusions:
Since some of the analyzed yolk components (e.g. testosterone and lutein) are known to exert sex-specific phenotypic effects on the progeny in this species, the lack of sex-specific egg allocation by mothers may either result from trade-offs between contrasting effects of different egg components on male and female offspring, or indicate that sex-specific traits are controlled primarily by mechanisms of sexual differentiation, including endogenous hormone production or metabolism of exogenous antioxidants, during embryonic development.
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Sex-inducing effect of a hydrophilic fraction on reproductive switching in the planarian Dugesia ryukyuensis (Seriata, Tricladida)
Background:
The mechanisms underlying the switching from an asexual to a sexual mode of reproduction, and vice versa, remain unknown in metazoans. In planarians, asexual worms acquire cryptic sexuality when fed with sexual worms, indicating that sexual worms contain a sex-inducing substance. Although such a chemical compound will provide clues about the mechanisms underlying the switching, information on the sex-inducing substance is poor. In order to identify this substance, we have established an assay system for sexual induction in asexual worms of Dugesia ryukyuensis by feeding them with sexual worms. Here, we carried out an isolation study on the sex-inducing substance using this assay system.
Results:
After centrifugation of sexual worms homogenised in saline solution, we found that not only did the precipitate have a sex-inducing effect on the asexual worms, which has been shown previously, but the cytosolic fraction did as well. We confirmed that the sex-inducing activity in the cytosolic fraction was recovered in a hydrophilic fraction separated on an octadecylsilane (ODS) column. We showed that the sex-inducing substance in the hydrophilic fraction is papain-resistant and a putative low-molecular-weight compound of less than 500. We also suggest the presence of an enhancer of sexual induction with a molecular weight (MW) of more than 5 K in the hydrophilic fraction.
Conclusion:
Our experiments showed the existence of a sex-inducing substance and an enhancer of sex-induction in a hydrophilic fraction, and a putative hydrophobic sex-inducing substance in the precipitate. Sexual induction in the asexual worms might be triggered by additive or synergistic effects of these chemical compounds.
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Genetic Vaccines and Therapy - Latest Articles
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Molecular Relationship between Field and Vaccine Strain of Measles Virus and its Persistence in Pakistan
Background:
Countrywide 5.9 million, 0-11 Month old children are immunized annually by EPI (Expended Program on Immunization) against 8 vaccine preventable diseases including measles and so on. Unfortunately the basic immunity centers are not uniform throughout the country. Each center provides services to about 27000 people which is inadequate. The purpose of this study was to explore the development of EPI Pakistan in terms of immunization of measles.
Methods:
Nucleotide sequences were analyzed by neighbor joining method (bootstrap test) using Bio- edit and MEGA-5 software to find evolutionary relationship between wild type measles strain and vaccine strain (Edmonston strain) used in Pakistan. For statistical analysis of data SPSS 16 was used.
Results:
Currently 1.3 vaccinators are working at each U C (union council) which according to national EPI policy should be at least 2. About 56% and 44% children of age 0-11 months did not received second dose of measles in the last two years respectively. Out of these 4231 cases which were reported last year, 1370 have received their first dose of measles vaccine.
Conclusion:
Seroconversion and seroprevalence study of the vaccine and field strain of measles virus is needed to confirm whether its failure is due to service unavailability or vaccine in-affectivity.Key words: Measles, EPI, Outbreaks, Immunization, vaccines, Pakistan.
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HCV entry receptor as potential targets for siRNA based inhibition of HCV
Background:
Hepatitis C virus (HCV) is a major health concern with almost 3% of the world's population (350 million individuals) and 10% of the Pakistani population chronically infected with this viral pathogen. The current therapy of interferon-α and ribavirin against HCV has limited efficiency, so alternative options are desperately needed. RNA interference (RNAi), which results in a sequence-specific degradation of HCV RNA has potential as a powerful alternative molecular therapeutic approach. Concerning viral entry, the HCV structural gene E2 is mainly involved in virus attachment to the host cell surface receptors i.e., CD81 tetraspanin, scavenger receptor class B type 1 (SR-B1), low density lipoprotein receptor (LDLR) and claudin1 (CLDN1).
Results:
In this report, we studied the relationship of the HCV receptors CD81, LDL, CLDN1 and SR-B1to HCV infection. The potential of siRNAs to inhibit HCV-3a replication in serum-infected Huh-7 cells was demonstrated by treatment with siRNAs against HCV receptors, which resulted in a significant decrease in HCV viral copy number.
Conclusions:
Our data clearly demonstrate that the RNAi-mediated silencing of HCV receptors is among the first of its type for the development of an effective siRNA-based therapeutic option against HCV-3a. These findings will shed further light on the possible role of receptors in inhibition of HCV-3a viral titre through siRNA mediated silencing.
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Occult HCV or delayed viral clearance from lymphocytes of Chronic HCV genotype 3 patients after interferon therapy
Background:
A recently discovered occult HCV entity reported by various investigators seems to be highly controversial. Especially, the clinical significance of these findings remains uncertain. For optimal outcome of antiviral therapy, investigation of occult HCV needs a broad-based probe in order to investigate the results of viral therapy and its host/viral interaction. The current study was aimed at determining the prevalence of occult HCV in peripheral blood lymphocytes of predominantly genotype 3 HCV-infected patients after completion of antiviral therapy and to investigate long term outcomes in the presence or absence of PBMC positivity.MethodA total of 151 chronic, antiHCV and serum RNA-positive patients were enrolled in the study. Patients with a complete virological response at the end of treatment were screened for the presence of viral RNA in their PBMCs and were followed for up to one year for the presence of serum and PBMC viral genomic RNA.
Results:
Out of 151 patients, 104 (70%) responded to the prescribed interferon treatment and showed viral-clearance from serum. These were screened for the presence of genomic RNA in their PBMCs. Sixteen samples were PBMC-positive for viral RNA at the end of treatment (EOT). All these patients had also cleared the virus from peripheral blood cells after the 6-12 month follow-up study.
Conclusion:
True occult hepatitis C virus does not exist in our cohort. Residual viremia at the EOT stage merely reflects a difference in viral kinetics in various compartments that remains a target of immune response even after the end of antiviral therapy and is eventually cleared out at the sustained viral response (SVR).
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Biodistribution and blood clearance of plasmid DNA administered in arginine peptide complexes
Background:
Peptide/DNA complexes have great potential as non-viral methods for gene delivery. Despite promising results for peptide-mediated gene delivery technology, an effective systemic peptide-based gene delivery system has not yet been developed.
Methods:
This study used pCMV-Luc as a model gene to investigate the biodistribution and the in vivo efficacy of arginine peptide-mediated gene delivery by polymerase chain reaction (PCR).
Results:
Plasmid DNA was detected in all organs tested 1 h after intraperitoneal administration of arginine/DNA complexes, indicating that the arginine/DNA complexes disseminated widely through the body. The plasmid was primarily detected in the spleen, kidney, and diaphragm 24 h post administration. The mRNA expression of plasmid DNA was noted in the spleen, kidney, and diaphragm for up to 2 weeks, and in the other major organs, for at least 1 week. Blood clearance studies showed that injected DNA was found in the blood as long as 6 h after injection.
Conclusions:
Taken together, our results demonstrated that arginine/DNA complexes are stable in blood and are effective for in vivo gene delivery. These findings suggest that intraperitoneal administration of arginine/DNA complexes is a promising tool in gene therapy.
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Establishment of stable Huh-7 cell lines expressing various hepatitis C virus genotype 3a protein: an in-vitro testing system for novel anti-HCV drugs
Background:
Hepatitis C virus (HCV) infection is the leading cause of chronic hepatitis which progresses to hepatocellular carcinoma (HCC) afflicting > 170 million people worldwide. HCV 3a is the most common genotype (about 70% of all genotypes) circulating in Pakistan. Expression of HCV individual gene of 3a would facilitate therapeutic and vaccines strategies against chronic HCV and liver Cirrhosis. The aim of the present study was the establishment of stable Huh-7 cell lines expressing structural and non structural proteins of HCV Genotype 3a Pakistani isolate obtained from chronic HCV patients.
Methods:
Blood samples were obtained from chronic HCV-3a positive patients. HCV individual genes were amplified using PCR with gene specific primers having restriction sites. These gene amplicons were cloned in mammalian expression vector PcDNA3.1+. Huh-7 cell lines were transfected with these constructed plasmids having structural or non-structural HCV genes in confluent cells with lipofectamine. Positive clones were selected with G418 and then confirmed by genome PCR. Subsequently, transcription and expression of the integrated genes were demonstrated by RT-PCR, sequencing and Western blot analysis.
Results:
We successfully cloned and express five HCV-3a genes in PcDNA3.1+ mammalian expression vector. Results of western blot and sequencing PCR confirmed the stable expression of these five genes.
Conclusion:
The stable cell-lines expressing HCV-3a individual genes would be a useful tool to investigate the role of various HCV proteins on HCV disease outcome and testing of new therapeutic strategies against HCV.
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Antiviral drugs against Hepatitis C Virus
Hepatitis C virus (HCV) infection is a major worldwide problem causes acute and chronic HCV infection. Current treatment of HCV includes pegylated interferon-α (PEG IFN- α) plus ribavirin (RBV) which has significant side effects depending upon the type of genotype. Currently, there is a need to develop antiviral agents, both from synthetic chemistry and Herbal sources. In the last decade, various novel HCV replication, helicase and entry inhibitors have been synthesized and some of which have been entered in different phases of clinical trials. Successful results have been acquired by executing combinational therapy of compounds with standard regime in different HCV replicons. Even though, diverse groups of compounds have been described as antiviral targets against HCV via Specifically Targeted Antiviral Therapy for hepatitis C (STAT-C) approach (in which compounds are designed to directly block HCV or host proteins concerned in HCV replication), still there is a need to improve the properties of existing antiviral compounds. In this review, we sum up potent antiviral compounds against entry, unwinding and replication of HCV and discussed their activity in combination with standard therapy. Conclusively, further innovative research on chemical compounds will lead to consistent standard therapy with fewer side effects.
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Comparative analysis of macrophage associated vectors for use in genetic vaccine.
Background:
Antigen presentation by non professional antigen presenting cells (APC) can lead to anergy. In genetic vaccines, targeting the macrophages and APC for efficient antigen presentation might lead to balanced immune response. One such approach is to incorporate APC specific promoter in the vector to be used.
Methods:
Three promoters known to be active in macrophage were selected and cloned in mammalian expressing vector (pAcGFP1-N1) to reconstruct (pAcGFP-MS), (pAcGFP-EMR) and (pAcGFP-B5I) with macrosialin, EmrI and Beta-5 Integrin promoters respectively. As a positive control (pAcGFP-CMV) was used with CMV promoter and promoterless vector (pAcGFP-NIX) which served as a negative control. GFP gene was used as readout under the control of each of the promoter. The expression of GFP was analyzed on macrophage and non-macrophage cell lines using Flow cytometry and qRT-PCR with TaqMan probe chemistries.
Results:
All the promoters in question were dominant to macrophage lineage cell lines as observed by fluorescence, Western blot and quantitative RT-PCR. The activity of macrosialin was significantly higher than other macrophage promoters. CMV promoter showed 1.83 times higher activity in macrophage cell lines. The expression of GFP driven by macrosialin promoter after 24 hours was 4.40 times higher in macrophage derived cell lines in comparison with non macrophage cell lines.
Conclusions:
Based on this study, macrosialin promoter can be utilized for targeting macrophage dominant expression. In vivo study needs to be carried out for its utility as a vaccine candidate.
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A comparison of multiple shRNA expression methods for combinatorial RNAi
RNAi gene therapies for HIV-1 will likely need to employ multiple shRNAs to counter resistant strains. We evaluated 3 shRNA co-expression methods to determine their suitability for present use; multiple expression vectors, multiple expression cassettes and single transcripts comprised of several dsRNA units (aka domains) with each being designed to a different target. Though the multiple vector strategy was effective with 2 shRNAs, the increasing number of vectors required is a major shortcoming. With single transcript configurations we only saw adequate activity from 1 of 10 variants tested, the variants being comprised of 2 - 3 different target domains. Whilst single transcript configurations have the most advantages on paper, these configurations can not yet be rapidly and reliably re-configured for new targets. However, our multiple cassette combinations of 2, 3 and 4 (29 bp) shRNAs were all successful, with suitable activity maintained in all positions and net activities comparable to that of the corresponding single shRNAs. We conclude that the multiple cassette strategy is the most suitably developed for present use as it is easy to design, assemble, is directly compatible with pre-existing shRNA and can be easily expanded.
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Altering alpha-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism
Background:
The envelope glycoprotein of lymphocytic choriomeningitis virus (LCMV) can efficiently pseudotype lentiviral vectors. Some strains of LCMV exploit high affinity interactions with α-dystroglycan (α-DG) to bind to cell surfaces and subsequently fuse in low pH endosomes. LCMV strains with low α-DG affinity utilize an unknown receptor and display unique tissue tropisms. We pseudotyped non-primate feline immunodeficiency virus (FIV) vectors using LCMV derived glycoproteins with high or low affinity to α-DG and evaluated their properties in vitro and in vivo.
Methods:
We pseudotyped FIV with the LCMV WE54 strain envelope glycoprotein and also engineered a point mutation in the WE54 envelope glycoprotein (L260F) to diminish α-DG affinity and direct binding to alternate receptors. We hypothesized that this change would alter in vivo tissue tropism and enhance gene transfer to neonatal animals.
Results:
In mice, hepatic α- and β-DG expression was greatest at the late gestational and neonatal time points. When displayed on the surface of the FIV lentivirus the WE54 L260F mutant glycoprotein bound weakly to immobilized α-DG. Additionally, LCMV WE54 pseudotyped FIV vector transduction was neutralized by pre-incubation with soluble α-DG, while the mutant glycoprotein pseudotyped vector was not. In vivo gene transfer in adult mice with either envelope yielded low transduction efficiencies in hepatocytes following intravenous delivery. In marked contrast, neonatal gene transfer with the LCMV envelopes, and notably with the FIV-L260F vector, conferred abundant liver and lower level cardiomyocyte transduction as detected by luciferase assays, bioluminescent imaging, and β-galactosidase staining.
Conclusions:
These results suggest that a developmentally regulated receptor for LCMV is expressed abundantly in neonatal mice. LCMV pseudotyped vectors may have applications for neonatal gene transfer.AbbreviationsArmstrong 53b (Arm53b); baculovirus Autographa californica GP64 (GP64); charge-coupled device (CCD); dystroglycan (DG); feline immunodeficiency virus (FIV); glycoprotein precursor (GP-C); firefly luciferase (Luc); lymphocytic choriomeningitis virus (LCMV); nuclear targeted β-galactosidase (ntLacZ); optical density (OD); PBS/0.1% (w/v) Tween-20 (PBST); relative light units (RLU); Rous sarcoma virus (RSV); transducing units per milliliter (TU/ml); vesicular stomatitis virus (VSV-G); wheat germ agglutinin (WGA); 50% reduction in binding (C50).
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In-vitro model systems to study Hepatitis C Virus
Hepatitis C virus (HCV) is a major cause of chronic liver diseases including steatosis, cirrhosis and hepatocellular carcinoma. Currently, there is no vaccine available for prevention of HCV infection due to high degree of strain variation. The current treatment of care, Pegylated interferon α in combination with ribavirin is costly, has significant side effects and fails to cure about half of all infections. The development of in-vitro models such as HCV infection system, HCV sub-genomic replicon, HCV producing pseudoparticles (HCVpp) and infectious HCV virion provide an important tool to develop new antiviral drugs of different targets against HCV. These models also play an important role to study virus lifecycle such as virus entry, endocytosis, replication, release and HCV induced pathogenesis. This review summarizes the most important in-vitro models currently used to study future HCV research as well as drug design.
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Geochemical Transactions - Latest Articles
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Geochemically induced shifts in catabolic energy yields explain past ecological changes of diffuse vents in the East Pacific Rise 9 degrees 50'N area
The East Pacific Rise (EPR) at 9 degrees 50'N hosts a hydrothermal vent field (Bio9) where the change in fluid chemistry is believed to have caused the demise of a tubeworm colony. We test this hypothesis and expand on it by providing a thermodynamic perspective in calculating free energies for a range of catabolic reactions from published compositional data. The energy calculations show that there was excess H2S in the fluids and that oxygen was the limiting reactant from 1991 to 1997. Energy levels are generally high, although they declined in that time span. In 1997, sulfide availability decreased substantially and H2S was the limiting reactant. Energy availability dropped by a factor of 10 to 20 from what it had been between 1991 and 1995. The perishing of the tubeworm colonies began in 1995 and coincided with the timing of energy decrease for sulfide oxidizers. In the same time interval, energy availability for iron oxidizers increased by a factor of 6 to 8, and, in 1997, there was 25 times more energy per transferred electron in iron oxidation than in sulfide oxidation. This change coincides with a massive spread of red staining (putative colonization by Fe-oxidizing bacteria) between 1995 and 1997.For a different cluster of vents from the EPR 9 degrees 50'N area (Tube Worm Pillar), thermodynamic modeling is used to examine changes in subseafloor catabolic metabolism between 1992 and 2000. These reactions are deduced from deviations in diffuse fluid compositions from conservative behavior of redox-sensitive species. We show that hydrogen is significantly reduced relative to values expected from conservative mixing. While H2 concentrations of the hydrothermal endmember fluids were constant between 1992 and 1995, the affinities for hydrogenotrophic reactions in the diffuse fluids decreased by a factor of 15 and then remained constant between 1995 and 2000. Previously, these fluids have been shown to support subseafloor methanogenesis. Our calculation results corroborate these findings and indicate that the 1992-1995 period was one of active growth of hydrogenotrophic communities, while the system was more or less at steady state between 1995 and 2000.
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The Effect of the CO3^(2-) to Ca^(2+) Ion Activity Ratio on Calcite Precipitation Kinetics and Sr^(2+) partitioning
Background:
A proposed strategy for immobilizing trace metals in the subsurface is to stimulate calcium carbonate precipitation and incorporate contaminants by co-precipitation. Such an approach will require injecting chemical amendments into the subsurface to generate supersaturated conditions that promote mineral precipitation. However, the formation of reactant mixing zones will create gradients in both the saturation state and ion activity ratios (i.e.,a_(CO_3^(2-) )a_(Ca^(2+) ) ). To better understand the effect of ion activity ratios on CaCO3 precipitation kinetics and Sr2+ co-precipitation, experiments were conducted under constant composition conditions where the supersaturation state (Omega) for calcite was held constant at 9.4, but the ion activity ratio (r= a_(CO_3^(2-) )a_(Ca^(2+) ) ) was varied between 0.0032 and 4.15.
Results:
Calcite was the only phase observed, by XRD, at the end of the experiments. Precipitation rates increased from 41.3+/-3.4 mumol m-2 min-1 at r = 0.0315 to a maximum rate of 74.5+/-4.8 mumol m-2 min-1 at r = 0.306 followed by a decrease to 46.3+/-9.6 mumol m-2 min-1 at r = 1.822. The trend was simulated using a simple mass transfer model for solute uptake at the calcite surface. However, precipitation rates at fixed saturation states also evolved with time. Precipitation rates accelerated for low r values but slowed for high r values. These trends may be related to changes in effective reactive surface area. The a_(CO_3^(2-) )a_(Ca^(2+) ) ratios did not affect the distribution coefficient for Sr in calcite (DPSr2+), apart from the indirect effect associated with the established positive correlation between DPSr2+ and calcite precipitation rate.
Conclusion:
At a constant supersaturation state (Omega = 9.4), varying the ion activity ratio affects the calcite precipitation rate. This behavior is not predicted by affinity-based rate models. Furthermore, at the highest ion ratio tested, no precipitation was observed, while at the lowest ion ratio precipitation occurred immediately and valid rate measurements could not be made. The maximum measured precipitation rate was 2-fold greater than the minima, and occurred at a carbonate to calcium ion activity ratio of 0.306. These findings have implications for predicting the progress and cost of remediation operations involving enhanced calcite precipitation where mineral precipitation rates, and the spatial/temporal distribution of those rates, can have significant impacts on the mobility of contaminants.
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Experimental Study of Cement-Sandstone/Shale-Brine-CO2 Interactions
Background:
Reactive-transport simulation is a tool that is being used to estimate long-term trapping of CO2, and wellbore and cap rock integrity for geologic CO2 storage. We reacted end member components of a heterolithic sandstone and shale unit that forms the upper section of the In Salah Gas Project carbon storage reservoir in Krechba, Algeria with supercritical CO2, brine, and with/without cement at reservoir conditions to develop experimentally constrained geochemical models for use in reactive transport simulations.
Results:
We observe marked changes in solution composition when CO2 reacted with cement, sandstone, and shale components at reservoir conditions. The geochemical model for the reaction of sandstone and shale with CO2 and brine is a simple one in which albite, chlorite, illite and carbonate minerals partially dissolve and boehmite, smectite, and amorphous silica precipitate. The geochemical model for the wellbore environment is also fairly simple, in which alkaline cements and rock react with CO2-rich brines to form an Fe containing calcite, amorphous silica, smectite and boehmite or amorphous Al(OH)3.
Conclusions:
Our research shows that relatively simple geochemical models can describe the dominant reactions that are likely to occur when CO2 is stored in deep saline aquifers sealed with overlying shale cap rocks, as well as the dominant reactions for cement carbonation at the wellbore interface.
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Inducing mineral precipitation in groundwater by addition of phosphate
Background:
Induced precipitation of phosphate minerals to scavenge trace elements from groundwater is a potential remediation approach for contaminated aquifers. The success of engineered precipitation schemes depends on the particular phases generated, their rates of formation, and their long term stability. The purpose of this study was to examine the precipitation of calcium phosphate minerals under conditions representative of a natural groundwater. Because microorganisms are present in groundwater, and because some proposed schemes for phosphate mineral precipitation rely on stimulation of native microbial populations, we also tested the effect of bacterial cells (initial densities of 105 and 107 mL-1) added to the precipitation medium. In addition, we tested the effect of a trace mixture of propionic, isovaleric, formic and butyric acids (total concentration 0.035 mM).
Results:
The general progression of mineral precipitation was similar under all of the study conditions, with initial formation of amorphous calcium phosphate, and transformation to poorly crystalline hydroxylapatite (HAP) within one week. The presence of the bacterial cells appeared to delay precipitation, although by the end of the experiments the overall extent of precipitation was similar for all treatments. The stoichiometry of the final precipitates as well as Rietveld structure refinement using x-ray diffraction data indicated that the presence of organic acids and bacterial cells resulted in an increasing a and decreasing c lattice parameter, with the higher concentration of cells resulting in the greatest distortion. Uptake of Sr into the solids was decreased in the treatments with cells and organic acids, compared to the control.
Conclusions:
Our results suggest that the minerals formed initially during an engineered precipitation application for trace element sequestration may not be the ones that control long-term immobilization of the contaminants. In addition, the presence of bacterial cells appears to be associated with delayed HAP precipitation, changes in the lattice parameters, and reduced incorporation of trace elements as compared to cell-free systems. Schemes to remediate groundwater contaminated with trace metals that are based on enhanced phosphate mineral precipitation may need to account for these phenomena, particularly if the remediation approach relies on enhancement of in situ microbial populations.
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Geophysical monitoring and reactive transport modeling of ureolytically-driven calcium carbonate precipitation
Ureolytically-driven calcium carbonate precipitation is the basis for a promising in-situ remediation method for sequestration of divalent radionuclide and trace metal ions. It has also been proposed for use in geotechnical engineering for soil strengthening applications. Monitoring the occurrence, spatial distribution, and temporal evolution of calcium carbonate precipitation in the subsurface is critical for evaluating the performance of this technology and for developing the predictive models needed for engineering application. In this study, we conducted laboratory column experiments using natural sediment and groundwater to evaluate the utility of geophysical (complex resistivity and seismic) sensing methods, dynamic synchrotron x-ray computed tomography (micro-CT), and reactive transport modeling for tracking ureolytically-driven calcium carbonate precipitation processes under site relevant conditions. Reactive transport modeling with TOUGHREACT successfully simulated the changes of the major chemical components during urea hydrolysis. Even at the relatively low level of urea hydrolysis observed in the experiments, the simulations predicted an enhanced calcium carbonate precipitation rate that was 3-4 times greater than the baseline level. Reactive transport modeling results, geophysical monitoring data and micro-CT imaging correlated well with reaction processes validated by geochemical data. In particular, increases in ionic strength of the pore fluid during urea hydrolysis predicted by geochemical modeling were successfully captured by electrical conductivity measurements and confirmed by geochemical data. The low level of urea hydrolysis and calcium carbonate precipitation suggested by the model and geochemical data was corroborated by minor changes in seismic P-wave velocity measurements and micro-CT imaging; the latter provided direct evidence of sparsely distributed calcium carbonate precipitation. Ion exchange processes promoted through NH4
+ production during urea hydrolysis were incorporated in the model and captured critical changes in the major metal species. The electrical phase increases were potentially due to ion exchange processes that modified charge structure at mineral/water interfaces. Our study revealed the potential of geophysical monitoring for geochemical changes during urea hydrolysis and the advantages of combining multiple approaches to understand complex biogeochemical processes in the subsurface.
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Formation of H2 and CH4 by weathering of olivine at temperatures between 30 and 70 degrees C
Hydrocarbons such as CH4 are known to be formed through the Fischer-Tropsch or Sabatier type reactions in hydrothermal systems usually at temperatures above 100°C. Weathering of olivine is sometimes suggested to account for abiotic formation of CH4 through its redox lowering and water splitting properties. Knowledge about the CH4 and H2 formation processes at low temperatures is important for the research about the origin and cause of early Earth and Martian CH4 and for CO2 sequestration. We have conducted a series of low temperature, long-term weathering experiments in which we have tested the CH4 and H2 formation potential of forsteritic olivine.The results show low temperature CH4 production that is probably influenced by chromite and magnetite as catalysts. Extensive analyses of a potential CH4 source trapped in the crystal structure of the olivine showed no signs of incorporated CH4. Also, the available sources of organic carbon were not enough to support the total amount of CH4 detected in our experiments. There was also a linear relationship between silica release into solution and the net CH4 accumulation into the incubation bottle headspaces suggesting that CH4 formation under these conditions could be a qualitative indicator of olivine dissolution.It is likely that minerals such as magnetite, chromite and other metal-rich minerals found on the olivine surface catalyze the formation of CH4, because of the low temperature of the system. This may expand the range of environments plausible for abiotic CH4 formation both on Earth and on other terrestrial bodies.
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Chromite oxidation by manganese oxides in subseafloor basalts and the presence of putative fossilized microorganisms
Chromite is a mineral with low solubility and is thus resistant to dissolution. The exception is when manganese oxides are available, since they are the only known naturally occurring oxidants for chromite. In the presence of Mn(IV) oxides, Cr(III) will oxidise to Cr(VI), which is more soluble than Cr(III), and thus easier to be removed. Here we report of chromite phenocrysts that are replaced by rhodochrosite (Mn(II) carbonate) in subseafloor basalts from the Koko Seamount, Pacific Ocean, that were drilled and collected during the Ocean Drilling Program (ODP) Leg 197. The mineral succession chromite-rhodochrosite-saponite in the phenocrysts is interpreted as the result of chromite oxidation by manganese oxides. Putative fossilized microorganisms are abundant in the rhodochrosite and we suggest that the oxidation of chromite has been mediated by microbial activity. It has previously been shown in soils and in laboratory experiments that chromium oxidation is indirectly mediated by microbial formation of manganese oxides. Here we suggest a similar process in subseafloor basalts.
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A 50-year record of NOx and SO2 sources in precipitation in the Northern Rocky Mountains, USA
Ice-core samples from Upper Fremont Glacier (UFG), Wyoming, were used as proxy records for the chemical composition of atmospheric deposition. Results of analysis of the ice-core samples for stable isotopes of nitrogen (δ15N, ) and sulfur (δ34S, ), as well as and deposition rates from the late-1940s thru the early-1990s, were used to enhance and extend existing National Atmospheric Deposition Program/National Trends Network (NADP/NTN) data in western Wyoming. The most enriched δ34S value in the UFG ice-core samples coincided with snow deposited during the 1980 eruption of Mt. St. Helens, Washington. The remaining δ34S values were similar to the isotopic composition of coal from southern Wyoming. The δ15N values in ice-core samples representing a similar period of snow deposition were negative, ranging from -5.9 to -3.2 ‰ and all fall within the δ15N values expected from vehicle emissions. Ice-core nitrate and sulfate deposition data reflect the sharply increasing U.S. emissions data from 1950 to the mid-1970s.
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A demonstration of an affinity between pyrite and organic matter in a hydrothermal setting
One of the key-principles of the iron-sulphur world theory is to bring organic molecules close enough to interact with each other, using the surface of pyrite as a substrate in a hydrothermal setting. The present paper explores the relationship of pyrite and organic matter in a hydrothermal setting from the geological record; in hydrothermal calcite veins from Carboniferous limestones in central Ireland. Here, the organic matter is accumulated as coatings around, and through, pyrite grains. Most of the pyrite grains are euhedral-subhedral crystals, ranging in size from ca 0.1-0.5 mm in diameter, and they are scattered throughout the matrix of the vein calcite. The organic matter was deposited from a hydrothermal fluid at a temperature of at least 200°C, and gives a Raman signature of disordered carbon. This study points to an example from a hydrothermal setting in the geological record, demonstrating that pyrite can have a high potential for the concentration and accumulation of organic materials.
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Isolation and purification of Cu-free methanobactin from Methylosinus trichosporium OB3b
Background:
The isolation of highly pure copper-free methanobactin is a prerequisite for the investigation of the biogeochemical functions of this chalkophore molecule produced by methane oxidizing bacteria. Here, we report a purification method for methanobactin from Methylosinus trichosporium OB3b cultures based on reversed-phase HPLC fractionation used in combination with a previously reported resin extraction. HPLC eluent fractions of the resin extracted product were collected and characterized with UV-vis, FT-IR, and C-1s NEXAFS spectroscopy, as well as with elemental analysis and ESI-MS.
Results:
The results showed that numerous compounds other than methanobactin were present in the isolate obtained with resin extraction. Molar C/N ratios, mass spectrometry measurements, and UV-vis spectra indicated that methanobactin was only present in one of the HPLC fractions. On a mass basis, methanobactin carbon contributed only 32% to the total organic carbon isolated with resin extraction. Our spectroscopic results implied that besides methanobactin, the organic compounds in the resin extract comprised breakdown products of methanobactin as well as polysaccharide-like substances.
Conclusion:
Our results demonstrate that a purification step is indispensable in addition to resin extraction in order to obtain pure methanobactin. The proposed HPLC purification procedure is suitable for semi-preparative work and provides copper-free methanobactin.
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Globalization and Health - Latest Articles
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A Comparative Study of Allowable Pesticide Residue Levels on Produce in the United States
Background:
The U.S. imports a substantial and increasing portion of its fruits and vegetables. The U.S. Food and Drug Administration currently inspects less than one percent of import shipments. While countries exporting to the U.S. are expected to comply with U.S. tolerances, including allowable pesticide residue levels, there is a low rate of import inspections and few other incentives for compliance.
Methods:
This analysis estimates the quantity of excess pesticide residue that could enter the U.S. if exporters followed originating country requirements but not U.S. pesticide tolerances, for the top 20 imported produce items based on quantities imported and U.S. consumption levels. Pesticide health effects data are also shown.
Results:
The model estimates that for the identified items, 120 439 kg of pesticides in excess of U.S. tolerances could potentially be imported to the U.S., in cases where U.S. regulations are more protective than those of originating countries. This figure is in addition to residues allowed on domestic produce. In the modeling, the top produce item, market, and pesticide of concern were oranges, Chile, and Zeta-Cypermethrin. Pesticides in this review are associated with health effects on 13 body systems, and some are associated with carcinogenic effects.
Conclusions:
There is a critical information gap regarding pesticide residues on produce imported to the U.S. Without a more thorough sampling program, it is not possible accurately to characterize risks introduced by produce importation. The scenario presented herein relies on assumptions, and should be considered illustrative. The analysis highlights the need for additional investigation and resources for monitoring, enforcement, and other interventions, to improve import food safety and reduce pesticide exposures in originating countries.
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Descriptive Review and Evaluation of the Functioning of the International Health Regulations (IHR) Annex 2
Background:
The International Health Regulations (IHRs) (2005) was developed with the aim of governing international responses to public health risks and emergencies. The document requires all 194 World Health Organization (WHO) Member States to detect, assess, notify and report any potential public health emergency of international concern (PHEIC) under specific timelines. Annex 2 of the IHR outlines decision-making criteria for State-appointed National Focal Points (NFP) to report potential PHEICs to the WHO, and is a critical component to the effective functioning of the IHRs.
Methods:
The aim of the study was to review and evaluate the functioning of Annex 2 across WHO-reporting States Parties. Specific objectives were to ascertain NFP awareness and knowledge of Annex 2, practical use of the tool, activities taken to implement it, its perceived usefulness and user-friendliness. Qualitative telephone interviews, followed by a quantitative online survey, were administered to NFPs between October, 2009 and February, 2010.
Results:
A total of 29 and 133 NFPs participated in the qualitative and quantitative studies, respectively. Qualitative interviews found most NFPs had a strong working knowledge of Annex 2; perceived the tool to be relevant and useful for guiding decisions; and had institutionalized management, legislation and communication systems to support it. NFPs also perceived Annex 2 as human and disease-centric, and emphasized its reduced applicability to potential PHEICs involving bioterrorist attacks, infectious diseases among animals, radio-nuclear and chemical spills, and water- or food-borne contamination. Among quantitative survey respondents, 88% reported having excellent/good knowledge of Annex 2; 77% reported always/usually using Annex 2 for assessing potential PHEICs; 76% indicated their country had some legal, regulatory or administrative provisions for using Annex 2; 95% indicated Annex 2 was always/usually useful for facilitating decisions regarding notifiability of potential PHEICs.
Conclusion:
This evaluation, including a large sample of WHO-reporting States Parties, found that the IHR's Annex 2 is perceived as useful for guiding decisions about notifiability of potential PHEICs. There is scope for the WHO to expand training and guidance on application of the IHR's Annex 2 to specific contexts. Continued monitoring and evaluation of the functioning of the IHR is imperative to promoting global health security.
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Multi-Country Analysis of Palm Oil Consumption and Cardiovascular Disease Mortality for Countries at Different Stages of Economic Development: 1980-1997
Background:
Cardiovascular diseases represent an increasing share of the global disease burden. There is concern that increased consumption of palm oil could exacerbate mortality from ischemic heart disease (IHD) and stroke, particularly in developing countries where it represents a major nutritional source of saturated fat.
Methods:
The study analyzed country-level data from 1980-1997 derived from the World Health Organization's Mortality Database, U.S. Department of Agriculture international estimates, and the World Bank (234 annual observations; 23 countries). Outcomes included mortality from IHD and stroke for adults aged 50 and older. Predictors included per-capita consumption of palm oil and cigarettes and per-capita Gross Domestic Product as well as time trends and an interaction between palm oil consumption and country economic development level. Analyses examined changes in country-level outcomes over time employing linear panel regressions with country-level fixed effects, population weighting, and robust standard errors clustered by country. Sensitivity analyses included further adjustment for other major dietary sources of saturated fat.
Results:
In developing countries, for every additional kilogram of palm oil consumed per-capita annually, IHD mortality rates increased by 68 deaths per 100,000 (95% CI [21-115]), whereas, in similar settings, stroke mortality rates increased by 19 deaths per 100,000 (95% CI [-12-49]) but were not significant. For historically high-income countries, changes in IHD and stroke mortality rates from palm oil consumption were smaller (IHD: 17 deaths per 100,000 (95% CI [5.3-29]); stroke: 5.1 deaths per 100,000 (95% CI [-1.2-11.0])). Inclusion of other major saturated fat sources including beef, pork, chicken, coconut oil, milk cheese, and butter did not substantially change the differentially higher relationship between palm oil and IHD mortality in developing countries.
Conclusions:
Increased palm oil consumption is related to higher IHD mortality rates in developing countries. Palm oil consumption represents a saturated fat source relevant for policies aimed at reducing cardiovascular disease burdens.
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Chronic Non-communicable Diseases in Cameroon- burden, determinants and current policies
Cameroon is experiencing an increase in the burden of chronic non-communicable diseases (NCDs), which accounted for 43% of all deaths in 2002. This article reviews the published literature to critically evaluate the evidence on the frequency, determinants and consequences of NCDs in Cameroon, and to identify research, intervention and policy gaps. The rising trends in NCDs have been documented for hypertension and diabetes, with a 2-5 and a 10-fold increase in their respective prevalence between 1994 and 2003. Magnitudes are much higher in urban settings, where increasing prevalence of overweight/obesity (by 54-82%) was observed over the same period. These changes largely result from the adoption of unfavorable eating habits, physical inactivity, and a probable increasing tobacco use. These behavioral changes are driven by the economic development and social mobility, which are part of the epidemiologic transition. There is still a dearth of information on chronic respiratory diseases and cancers, as well as on all NDCs and related risk factors in children and adolescents. More nationally representative data is needed to tract risk factors and consequences of NCDs. These conditions are increasingly been recognized as a priority, mainly through locally generated evidence. Thus, national-level prevention and control programs for chronic diseases (mainly diabetes and hypertension) have been established. However, the monitoring and evaluation of these programs is necessary. Budgetary allocations data by the ministry of health would be helpful, to evaluate the investment in NCDs prevention and control. Establishing more effective national-level tobacco control measures and food policies, as well as campaigns to promote healthy diets, physical activity and tobacco cessation would probably contribute to reducing the burden of NCDs.
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Social participation and healthy ageing: a neglected, significant protective factor for chronic non communicable conditions
Background:
Low and middle income countries are ageing at a much faster rate than richer countries, especially in Asia. This is happening at a time of globalisation, migration, urbanisation, and smaller families. Older people make significant contributions to their families and communities, but this is often undermined by chronic disease and preventable disability. Social participation can help to protect against morbidity and mortality. We argue that social participation deserves much greater attention as a protective factor, and that older people can play a useful role in the prevention and management of chronic conditions. We present, as an example, a low-cost, sustainable strategy that has increased social participation among elders in Sri Lanka.DiscussionCurrent international policy initiatives to address the increasing prevalence of non-communicable chronic diseases are focused on cardiovascular disease, diabetes, respiratory disease and cancers, responsible for much premature mortality. Interventions to modify their shared risk factors of high salt and fat diets, inactivity, smoking and alcohol use are advocated. But older people also suffer chronic conditions that primarily affect quality of life, and have a wider range of risk factors. There is strong epidemiological and physiological evidence that social isolation, in particular, is as important a risk factor for chronic diseases as the 'lifestyle' risk factors, yet it is currently neglected. There are useful experiences of inexpensive and sustainable strategies to improve social participation among older people in low and lower middle income countries. Our experience with forming Elders' Clubs with retired tea estate workers in Sri Lanka suggests many benefits, including social support and participation, inter-generational contact, a collective voice, and facilitated access to health promotion activities, and to health care and social welfare services.SummaryPolicies to address the increase in chronic non-communicable diseases should include consideration of healthy ageing, conditions that affect quality of life, and strategies to increase social participation. There are useful examples showing that it is feasible to catalyse the formation of Elders' Clubs or older people's associations which become self-sustaining, promote social participation, and improve health and well-being of elders and their families.
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Health system determinants of infant, child and maternal mortality: A cross-sectional study of UN member countries
ObjectiveFew studies have examined the link between health system strength and important public health outcomes across nations. We examined the association between health system indicators and mortality rates.
Methods:
We used mixed effects linear regression models to investigate the strength of association between outcome and explanatory variables, while accounting for geographic clustering of countries. We modelled infant mortality rate (IMR), child mortality rate (CMR), and maternal mortality rate (MMR) using 13 explanatory variables as outlined by the World Health Organization.
Results:
Significant protective health system determinants related to IMR included higher physician density (adjusted rate ratio [aRR] 0.81; 95% Confidence Interval [CI] 0.71-0.91), higher sustainable access to water and sanitation (aRR 0.85; 95% CI 0.78-0.93), and having a less corrupt government (aRR 0.57; 95% CI 0.40-0.80). Out-of-pocket expenditures on health (aRR 1.29; 95% CI 1.03-1.62) were a risk factor. The same four variables were significantly related to CMR after controlling for other variables. Protective determinants of MMR included access to water and sanitation (aRR 0.88; 95% CI 0.82-0.94), having a less corrupt government (aRR 0.49; 95%; CI 0.36-0.66), and higher total expenditures on health per capita (aRR 0.84; 95% CI 0.77-0.92). Higher fertility rates (aRR 2.85; 95% CI: 2.02-4.00) were found to be a significant risk factor for MMR.
Conclusion:
Several key measures of a health system predict mortality in infants, children, and maternal mortality rates at the national level. Improving access to water and sanitation and reducing corruption within the health sector should become priorities.
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The increasing chronicity of HIV in sub-Saharan Africa: Re-thinking "HIV as a long-wave event" in the era of widespread access to ART
HIV was first described as a "long-wave event" in 1990, well before the advent of antiretroviral therapy (ART). The pandemic was then seen as involving three curves: an HIV curve, an AIDS curve and a curve representing societal impact. Since the mid-2000's, free public delivery of life-saving ART has begun shifting HIV from a terminal disease to a chronic illness for those who can access and tolerate the medications. This increasing chronicity prompts revisiting HIV as a long-wave event. First, with widespread availability of ART, the HIV curve will be higher and last longer. Moreover, if patterns in sub-Saharan Africa mirror experiences in the North, people on ART will live far longer lives but with new experiences of disability. Disability, broadly defined, can result from HIV, its related conditions, and from side effects of medications. Individual experiences of disability will vary. At a population level, however, we anticipate that experiences of disability will become a common part of living with HIV and, furthermore, may be understood as a variation of the second curve. In the original conceptualization, the second curve represented the transition to AIDS; in the era of treatment, we can expect a transition from HIV infection to HIV-related disability for people on ART. Many such individuals may eventually develop AIDS as well, but after a potentially long life that includes fluctuating episodes of illness, wellness and disability. This shift toward chronicity has implications for health and social service delivery, and requires a parallel shift in thinking regarding HIV-related disability. A model providing guidance on such a broader understanding of disability is the World Health Organization's International Classification of Functioning, Disability and Health (ICF). In contrast to a biomedical approach concerned primarily with diagnoses, the ICF includes attention to the impact of these diagnoses on people's lives and livelihoods. The ICF also focuses on personal and environmental contextual factors. Locating disability as a new form of the second curve in the long-wave event calls attention to the new spectrum of needs that will face many people living with HIV in the years and decades ahead.
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Canadian medical tourism companies that have exited the marketplace: Content analysis of websites used to market transnational medical travel
Background:
Medical tourism companies play an important role in promoting transnational medical travel for elective, out-of-pocket medical procedures. Though researchers are paying increasing attention to the global phenomenon of medical tourism, to date websites of medical tourism companies have received limited scrutiny. This article analyzes websites of Canadian medical tourism companies that advertised international healthcare but ultimately exited the marketplace. Using content analysis of company websites as an investigative tool, the article provides a detailed account of medical tourism companies that were based in Canada but no longer send clients to international health care facilities.
Methods:
Internet searches, Google Alerts, searches on Google News Canada and ProQuest Newsstand, and searches of an Industry Canada database were used to locate medical tourism companies located in Canada. Once medical tourism companies were identified, the social science research method of content analysis was used to extract relevant information from company websites. Company websites were analyzed to determine: 1) where these businesses were based; 2) the destination countries and medical facilities that they promoted; 3) the health services they advertised; 4) core marketing messages; and 5) whether businesses marketed air travel, hotel accommodations, and holiday excursions in addition to medical procedures.
Results:
In total, 25 medical tourism companies that were based in Canada are now defunct. Given that an estimated 18 medical tourism companies and 7 regional, cross-border medical travel facilitators now operate in Canada, it appears that approximately half of all identifiable medical tourism companies in Canada are no longer in business. 13 of the previously operational companies were based in Ontario, 7 were located in British Columbia, 4 were situated in Quebec, and 1 was based in Alberta. 14 companies marketed medical procedures within a single country, 9 businesses marketed health care at 2 or more destination nations, and 2 companies did not specify particular health care destinations. 22 companies operated as "generalist" businesses marketing many different types of medical procedures. 3 medical tourism companies marketed "specialist" services restricted to dental procedures or organ transplants. In general, medical tourism companies marketed health services on the basis of access to affordable, timely, and high-quality care. 16 businesses offered to make travel arrangements, 20 companies offered to book hotel reservations, and 17 medical tourism companies advertised holiday excursions.
Conclusions:
This article provides a detailed empirical analysis of websites of medical tourism companies that were based in Canada but exited the marketplace and are now inoperative. The article identifies where these companies were located in Canada, what countries and health care facilities they selected as destination sites, the health services they advertised, how they marketed themselves in a competitive environment, and what travel-related services they promoted in addition to marketing health care. The paper reveals a fluid marketplace, with many medical tourism companies exiting this industry. In addition, by disclosing identities of companies, providing their websites, archiving these websites or print copies of websites for future studies, and analyzing content of medical tourism company websites, the article can serve as a useful resource for future studies. Citizens, health policy-makers, clinicians, and researchers can all benefit from increased insight into Canada's medical tourism industry.
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A win-win solution?: A critical analysis of tiered pricing to improve access to medicines in developing countries
Background:
Tiered pricing - the concept of selling drugs and vaccines in developing countries at prices systematically lower than in industrialized countries - has received widespread support from industry, policymakers, civil society, and academics as a way to improve access to medicines for the poor. We carried out case studies based on a review of international drug price developments for antiretrovirals, artemisinin combination therapies, drug-resistant tuberculosis medicines, liposomal amphotericin B (for visceral leishmaniasis), and pneumococcal vaccines.DiscussionWe found several critical shortcomings to tiered pricing: it is inferior to competition for achieving the lowest sustainable prices; it often involves arbitrary divisions between markets and/or countries, which can lead to very high prices for middle-income markets; and it leaves a disproportionate amount of decision-making power in the hands of sellers vis-à-vis consumers. In many developing countries, resources are often stretched so tight that affordability can only be approached by selling medicines at or near the cost of production. Policies that "de-link" the financing of R&D from the price of medicines merit further attention, since they can reward innovation while exploiting robust competition in production to generate the lowest sustainable prices. However, in special cases - such as when market volumes are very small or multi-source production capacity is lacking - tiered pricing may offer the only practical option to meet short-term needs for access to a product. In such cases, steps should be taken to ensure affordability and availability in the longer-term.SummaryTo ensure access to medicines for populations in need, alternate strategies should be explored that harness the power of competition, avoid arbitrary market segmentation, and/or recognize government responsibilities. Competition should generally be the default option for achieving affordability, as it has proven superior to tiered pricing for reliably achieving the lowest sustainable prices.
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The Growing Caseload of Chronic Life-Long Conditions Calls for a Move towards Full Self-Management in Low Income Countries
Background:
The growing caseload caused by patients with chronic life-long conditions leads to increased needs for health care providers and rising costs of health services, resulting in a heavy burden on health systems, populations and individuals. The professionalised health care for chronic patients common in high income countries is very labour-intensive and expensive. Moreover, the outcomes are often poor. In low-income countries, the scarce resources and the lack of quality and continuity of health care result in high health care expenditure and very poor health outcomes. The current proposals to improve care for chronic patients in low-income countries are still very much provider-centred.The aim of this paper is to show that present provider-centred models of chronic care are not adequate and to propose 'full self-management' as an alternative for low-income countries, facilitated by expert patient networks and smart phone technology.DiscussionPeople with chronic life-long conditions need to 'rebalance' their life in order to combine the needs related to their chronic condition with other elements of their life. They have a crucial role in the management of their condition and the opportunity to gain knowledge and expertise in their condition and its management. Therefore, people with chronic life-long conditions should be empowered so that they become the centre of management of their condition. In full self-management, patients become the hub of management of their own care and take full responsibility for their condition, supported by peers, professionals and information and communication tools.We will elaborate on two current trends that can enhance the capacity for self-management and coping: the emergence of peer support and expert-patient networks and the development and distribution of smart phone technology both drastically expand the possibilities for full self-management.
Conclusion:
Present provider-centred models of care for people with chronic life-long conditions are not adequate and we propose 'full self-management' as an alternative for low-income countries, supported by expert networks and smart phone technology.
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Harm Reduction Journal - Latest Articles
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Sex work involvement among women with long-term opioid injection drug dependence who enter opioid agonist treatment
Background:
Substitution with opioid-agonists (e.g., methadone) has shown to be an effective treatment for chronic long-term opioid dependency. Survival sex work, very common among injection drug users, has been associated with poor Opioid Agonist Treatment (OAT) engagement, retention and response. Therefore, this study was undertaken to determine factors associated with engaging in sex work among long-term opioid dependent women receiving OAT.
Methods:
Data from a randomized controlled trial, the North American Opiate Medication Initiative (NAOMI), conducted in Vancouver and Montreal (Canada) between 2005-2008, was analyzed. The NAOMI study compared the effectiveness of oral methadone to injectable diacetylmorphine or injectable hydromorphone, the last two on a double blind basis, over 12 months. A research team, independent of the clinic services, obtained outcome evaluations at baseline and follow-up (3, 6, 9, 12, 18 and 24 months).
Results:
A total of 53.6% of women reported engaging in sex work in at least one of the research visits. At treatment initiation, women who were younger and had fewer years of education were more likely to be engaged in sex work. The multivariate logistic generalized estimating equation regression analysis determined that psychological symptoms, and high illicit heroin and cocaine use correlated with women's involvement in sex work during the study period.
Conclusions:
After entering OAT, women using injection drugs and engaging in sex work represent a particularly vulnerable group showing poorer psychological health and a higher use of heroin and cocaine compared to women not engaging in sex work. These factors must be taken into consideration in the planning and provision of OAT in order to improve treatment outcomes.Trial Registration: NCT00175357
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Pharmacological interventions in the treatment of the acute effects of Cannabis: a systematic review of literature
Background:
Cannabis intoxication is related to a number of physical and mental health risks with ensuing social costs. However, little attention has been given to the investigation of possible pharmacological interactions in this condition. Objective: To review the available scientific literature concerning pharmacological interventions for the treatment of the acute effects of cannabis. Methods: A search was performed on the Pubmed, Lilacs, and Scielo online databases by combining the terms cannabis, intoxication, psychosis, anxiety, and treatment. The articles selected from this search had their reference lists checked for additional publications related to the topic of the review. Results: The reviewed articles consisted of case reports and controlled clinical trials and are presented according to interventions targeting the physiological, psychiatric, and cognitive symptoms provoked by cannabis. The pharmacological interventions reported in these studies include: beta-blockers, antiarrhythmic agents, antagonists of CB-1 and GABA-benzodiazepine receptors, antipsychotics, and cannabidiol. Conclusion: Although scarce, the evidence on pharmacological interventions for the management of cannabis intoxication suggests that propanolol and rimonabant are the most effective compounds currently available to treat the physiological and subjective effects of the drug. Further studies are necessary to establish the real effectiveness of these two medications, as well as the effectiveness of other candidate compounds to counteract the effects of cannabis intoxication, such as cannabidiol and flumazenil.
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Injecting drug use via femoral vein puncture: Preliminary findings of a point-of-care ultrasound service for opioid-dependent groin injectors in treatment
Background:
Within the UK, injecting in the femoral vein (FV), often called 'groin injecting', is a serious cause of risk and harm. This study aimed to use ultrasound scanning as a means to engage groin injectors (GIs), examine their femoral injecting sites and assess their venous health, with the intention of developing improved responses.
Methods:
Between September 2006 and March 2009, GIs attending a network of community drug treatment centres in South East England were invited to attend an ultrasound 'health-check' clinic. This paper provides a narrative account of the scanning procedure and operation of the service, with descriptive statistical analysis of GIs who attended. The analysis uses a structured, specially-developed clinical data set that incorporates a categorisation for the severity of FV damage. Case studies using ultrasound images and video are provided to illustrate the range of presentations encountered and the categorisations used for severity.
Results:
A total of 160 groin scans (76 bilateral and 8 unilateral) were performed in 84 GIs. The majority were men (69.0%) and the mean age of the sample was 36.8 years. The mean duration of drug use and injecting drug use was 19.7 years and 13.8 years, respectively. FV damage at the injecting site in the right groin was graded as minimal in 20 patients (25%), moderate in 27 (33.8%), severe in 16 (20.0%) and very-severe in 17 (21.3%). Corresponding figures for left FV were 24 (30.0%), 22 (27.5%), 18 (22.5%) and 16 (20.0%). Wide variation was observed in the time to the development of these grades of FV damage.
Conclusions:
Modern, portable ultrasound scanners make it possible to examine the venous health of GIs in community treatment settings. Ultrasound scanning identified extensive FV damage, much hitherto-unrecognised in this population. These findings should further alert clinicians, policy-makers and patients to the urgent need for effective harm reduction responses to GI behaviour. Images of damaged FV in this paper might prove to be a useful resource for discussions about GI risks.
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Implementation and Evaluation of a Harm-Reduction Model for Clinical Care of Substance Using Pregnant Women
Background:
Methamphetamine (MA) use during pregnancy is associated with many pregnancy complications, including preterm birth, small for gestational age, preeclampsia, and abruption. Hawaii has lead the nation in MA use for many years, yet prior to 2007, did not have a comprehensive plan to care for pregnant substance-using women. In 2006, the Hawaii State Legislature funded a pilot perinatal addiction clinic. The Perinatal Addiction Treatment Clinic of Hawaii was built on a harm-reduction model, encompassing perinatal care, transportation, child-care, social services, family planning, motivational incentives, and addiction medicine. We present the implementation model and results from our first one hundred three infants (103) seen over 3 years of operation of the program.
Methods:
Referrals came from community health centers, hospitals, addiction treatment facilities, private physician offices, homeless outreach services and self-referral through word-of-mouth and bus ads. Data to describe sample characteristics and outcome was obtained prospectively and retrospectively from chart abstraction and delivery data. Drug use data was obtained from the women's self-report and random urine toxicology during the pregnancy, as well as urine toxicology at the time of birth on mothers, and urine and meconium toxicology on the infants. Post-partum depression was measured in mothers with the Edinburgh Post-Partum depression scale. For comparison, data from Path clinic patients were compared with a representative cohort of women delivering at Kapiolani Medical Center for Women and Children during the same time frame, who were enrolled in another study of pregnancy outcomes. Ethical approval for this study was obtained through the University of Hawaii Committee for Human Studies.
Results:
Between April 2007 and August 2010, 213 women with a past or present history of addiction were seen, 132 were pregnant and 97 delivered during that time. 103 live-born infants were delivered. There were 3 first-trimester Spontaneous Abortions, two 28-week intrauterine fetal deaths, and two sets of twins and 4 repeat pregnancies. Over 50% of the women had lost custody of previous children due to substance use. The majority of women who delivered used methamphetamine (86%), either in the year before pregnancy or during pregnancy. Other drugs include marijuana (59.8%), cocaine (33%), opiates (9.6%), and alcohol (15.2%). Of the women served, 85% smoked cigarettes upon enrollment. Of the 97 women delivered during this period, all but 4 (96%) had negative urine toxicology at the time of delivery. Of the 103 infants, 13 (12.6%) were born preterm, equal to the state and national average, despite having many risk factors for prematurity, including poverty, poor diet, smoking and polysubstance use. Overwhelmingly, the women are parenting their children, >90% retained custody at 8 weeks. Long-term follow-up showed that women who maintained custody chose long-acting contraceptive methods; while those who lost custody had a very high (>50%) repeat pregnancy rate at 9 months post delivery.
Conclusion:
Methamphetamine use during pregnancy doesn't exist is isolation. It is often combined with a multitude of other adverse circumstances, including poverty, interpersonal violence, psychiatric comorbidity, polysubstance use, nutritional deficiencies, inadequate health care and stressful life experiences. A comprehensive harm reduction model of perinatal care, which aims to ameliorate some of these difficulties for substance-using women without mandating abstinence, provides exceptional birth outcomes and can be implemented with limited resources.
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Psychoactive substances and the political ecology of mental distress
The goal of this paper is to both understand and depathologize clinically significant mental distress related to criminalized contact with psychoactive biotic substances by employing a framework known as critical political ecology of health and disease from the subdiscipline of medical geography. The political ecology of disease framework joins disease ecology with the power-calculus of political economy and calls for situating health-related phenomena in their broad social and economic context, demonstrating how large-scale global processes are at work at the local level, and giving due attention to historical analysis in understanding the relevant human-environment relations. Critical approaches to the political ecology of health and disease have the potential to incorporate ever-broadening social, political, economic, and cultural factors to challenge traditional causes, definitions, and sociomedical understandings of disease. Inspired by the patient-centered medical diagnosis critiques in medical geography, this paper will use a critical political ecology of disease approach to challenge certain prevailing sociomedical interpretations of disease, or more specifically, mental disorder, found in the field of substance abuse diagnostics and the related American punitive public policy regimes of substance abuse prevention and control, with regards to the use of biotic substances. It will do this by first critically interrogating the concept of "substances" and grounding them in an ecological context, reviewing the history of both the development of modern substance control laws and modern substance abuse diagnostics, and understanding the biogeographic dimensions of such approaches. It closes with proposing a non-criminalizing public health approach for regulating human close contact with psychoactive substances using the example of cannabis use.
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The Nature of Methadone Diversion in England: A Merseyside case study
Background:
Methadone maintenance treatment (MMT) is a key element in treatment for opiate addiction; however concerns about the diversion of methadone remain. More current empirical data on methadone diversion are required. This research investigated the market for diverted methadone in Merseyside, UK, in order to provide a case study which can be transferred to other areas undertaking methadone maintenance treatment on a large scale. Methods: Questionnaires were completed (in interview format) with 886 past year users of methadone recruited both in and out of prescribing agencies. Topic areas covered included current prescribing, obtaining and providing methadone, reasons for using illicit methadone and other drug use. Results: Large proportions of participants had obtained illicit methadone for use in the past year with smaller proportions doing so in the past month. Proportions of participants buying and being given methadone were similar. Exchange of methadone primarily took place between friends and associates, with 'dealers' rarely involved. Gender, age, whether participant's methadone consumption was supervised and whether the aims of their treatment had been explained to them fully, influenced the extent to which participants were involved in diverting or using diverted methadone. Conclusion: Methadone diversion is widespread although drug users generally do not make use of illicit methadone regularly (every month). The degree of altruism involved in the exchange of methadone does not negate the potential role of this action in overdose or the possibility of criminal justice action against individuals. Treatment agencies need to emphasise these risks whilst ensuring that treatment aims are effectively shared with clients to ensure adherence to treatment.
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It Can't Hurt to Ask;
A Patient-Centered Quality of Service Assessment of Health Canada's Medical Cannabis Policy and Program
Background:
In 2001 Health Canada responded to a series of Ontario court decisions by creating the Marihuana Medical Access Division (MMAD) and the Marihuana Medical Access Regulations (MMAR). Although Health Canada has conducted a small number of stakeholder consultations, the federal government has never polled federally authorized cannabis patients. This study is an attempt to learn more about patient needs, challenges and experiences with the MMAD.
Methods:
Launched in the spring of 2007, Quality of Service Assessment of Health Canada's Medical Cannabis Policy and Program pairs a 50 question online survey addressing the personal experiences of patients in the federal cannabis program with 25 semi-guided interviews. Data gathering for this study took place from April 2007 to Jan. 2008, eventually garnering survey responses from 100 federally-authorized users, which at the time represented about 5% of the patients enrolled in Health Canada's program. This paper presents the results of the survey portion of the study.
Results:
8% of respondents report getting their cannabis from Health Canada, while 66% grow it for themselves. >50% report that they frequent compassion clubs or dispensaries, which remain illegal and unregulated in Canada. 81% of patients would chose certified organic methods of cultivation; >90% state that not all strains are equally effective at relieving symptoms, and 97% would prefer to obtain cannabis from a source where multiple strains are available. Of the 48 patients polled that had tried the Health Canada cannabis supply, >75% rank it as either "1" or "2" on a scale of 1-10 (with "1" being "very poor", and 10 being "excellent").Discussion72% of respondents report they are either "somewhat" or "totally unsatisfied" with Canada's medical cannabis program. These survey results and relevant court decisions suggest that the MMAR are not meeting the needs of most of the nation's medical cannabis patient community. It is hoped this research will help inform policy changes that will better address the needs of Canada's critically and chronically ill medical cannabis patient population, including the integration of community-based dispensaries into this novel healthcare delivery model.
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Prescribing Cannabis for Harm Reduction
Neuropathic pain affects between 5% and 10% of the US population and can be refractory to treatment. Opioids may be recommended as a second-line pharmacotherapy but have risks including overdose and death. Cannabis has been shown to be effective for treating nerve pain without the risk of fatal poisoning. The author suggests that physicians who treat neuropathic pain with opioids should evaluate their patients for a trial of cannabis and prescribe it when appropriate prior to using opioids. This harm reduction strategy may reduce the morbidity and mortality rates associated with prescription pain medications.
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The Soviet doctor and the treatment of drug addiction: "A difficult and most ungracious task"
This paper reviews the development of early Soviet drug treatment approaches by focusing on the struggle for disciplinary power between leading social and mental hygienists and clinical psychiatrists as a defining moment for Soviet drug treatment speciality that became known as "narcology." From this vantage point, I engage in the examination of the rise and fall of various treatment methods and conceptualizations of addiction in Russian metropolitan centres and look at how they were imported (or not) to other Soviet republics. As clinical psychiatrists appeared as undisputed victors from the battle with social and mental hygienists, the entire narcological arsenal was subdued in order to serve the needs of mainstream psychiatry. However, what that 'mainstream' would be, was not entirely clear. When, in 1934, Aleksandr Rapoport insisted on the need for re-working narcological knowledge in line with the Marxist approach, he could only raise questions and recognise that there were almost no "dialectically illuminated scientific data" to address these questions. The maintenance treatment of opiate users, which emerged as the most effective one based on the results of a six-year study published in 1936, was definitely not attuned to the political and ideological environment of the late 1930s. Maintenance was rather considered as a temporary solution, in the absence of radical therapeutic measures to free Soviet society from "narkomania." As the Great Terror swept across the Soviet Union, Stalin's regime achieved its objective of eliminating drug addiction from the surface of public life by driving opiate users deep underground and incarcerating many of them in prisons and the Gulag camps. In the final section, I briefly discuss the changing perceptions of drug use during the World War II and outline subsequent transformations in Soviet responses to the post-war opiate addiction.
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Non-medical use of opioids among HIV-infected opioid dependent individuals on opioid maintenance treatment: the need for a more comprehensive approach
Background:
Opioid maintenance treatment (OMT) has a positive impact on substance use and health outcomes among HIV-infected opioid dependent patients. The present study investigates non-medical use of opioids by HIV-infected opioid-dependent individuals treated with buprenorphine or methadone. Methods: The MANIF 2000 study is a longitudinal study that enrolled a cohort of 476 HIV-infected opioid-dependent individuals. Data were collected in outpatient hospital services delivering HIV care in France. The sample comprised all patients receiving OMT (either methadone or buprenorphine) who attended at least one follow-up visit with data on adherence to OMT (N=235 patients, 1056 visits). Non-medical use of opioids during OMT was defined as having reported use of opioids in a non-medical context, and/or the misuse of the prescribed oral OMT by an inappropriate route of administration (injection or sniffing). After adjusting for the non-random assignment of OMT type, a model based on GEE was then used to identify predictors of non-medical use of opioids. Results: Among the 235 patients, 144 (61.3%) and 91 (38.9%) patients were receiving buprenorphine and methadone, respectively, at baseline. Non-medical use of opioids was found in 41.6% of visits for 83% of individual patients. In the multivariate analysis, predictors of non-medical use of opioids were: cocaine, daily cannabis, and benzodiazepine use, experience of opioid withdrawal symptoms, and less time since OMT initiation. Conclusions: Non-medical use of opioids was found to be comparable in OMT patients receiving methadone or buprenorphine. The presence of opioid withdrawal symptoms was a determinant of non-medical use of opioids and may serve as a clinical indicator of inadequate dosage, medication, or type of follow-up. Sustainability and continuity of care with adequate monitoring of withdrawal symptoms and polydrug use may contribute to reduced harms from ongoing non-medical use of opioids.
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Head & Face Medicine - Latest Articles
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Movement of the external ear in human embryo
Background:
External ears, one of the major face components, show an interesting movement during craniofacial morphogenesis in human embryo. The present study was performed to see if movement of the external ears in a human embryo could be explained by differential growth.
Methods:
In all, 171 samples between Carnegie stage (CS) 17 and CS 23 were selected from MR image datasets of human embryos obtained from the Kyoto Collection of Human Embryos. The three-dimensional absolute position of 13 representative anatomical landmarks, including external and internal ears, from MRI data was traced to evaluate the movement between the different stages with identical magnification. Two different sets of reference axes were selected for evaluation and comparison of the movements.
Results:
When the pituitary gland and the first cervical vertebra were selected as a reference axis, the 13 anatomical landmarks of the face spread out within the same region as the embryo enlarged and changed shape. The external ear did move mainly laterally, but not cranially. The distance between the external and internal ear stayed approximately constant. Three-dimensionally, the external ear located in the caudal ventral parts of the internal ear in CS 17, moved mainly laterally until CS 23. When surface landmarks eyes and mouth were selected as a reference axis, external ears moved from the caudal lateral ventral region to the position between eyes and mouth during development.
Conclusion:
The results indicate that movement of all anatomical landmarks, including external and internal ears, can be explained by differential growth. Also, when the external ear is recognized as one of the facial landmarks and having a relative position to other landmarks such as the eyes and mouth, the external ears seem to move cranially.
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Magnetic resonance imaging, computed tomography, and 68Ga-DOTATOC positron emission tomography for imaging skull base meningiomas with infracranial extension treated with stereotactic radiotherapy - a case series
IntroductionMagnetic resonance imaging (MRI) and computed tomography (CT) with 68Ga-DOTATOC positron emission tomography (68Ga-DOTATOC-PET) were compared retrospectively for their ability to delineate infracranial extension of skull base (SB) meningiomas treated with fractionated stereotactic radiotherapy.
Methods:
Fifty patients with 56 meningiomas of the SB underwent MRI, CT, and 68Ga-DOTATOC PET/CT prior to fractionated stereotactic radiotherapy. The study group consisted of 16 patients who had infracranial meningioma extension, visible on MRI +/- CT (MRI/CT) or PET, and were evaluated further. The respective findings were reviewed independently, analyzed with respect to correlations, and compared with each other.
Results:
Within the study group, SB transgression was associated with bony changes visible by CT in 14 patients (81%). Tumorous changes of the foramen ovale and rotundum were evident in 13 and 8 cases, respectively, which were accompanied by skeletal muscular invasion in 8 lesions. We analysed six designated anatomical sites of the SB in each of the 16 patients. Of the 96 sites, 42 had infiltration that was delineable by MRI/CT and PET in 35 cases and by PET only in 7 cases. The mean infracranial volume that was delineable in PET was 10.1 +/- 10.6 cm3, which was somewhat larger than the volume detectable in MRI/CT (8.4 +/- 7.9 cm3).
Conclusions:
68Ga-DOTATOC-PET allows detection and assessment of the extent of infracranial meningioma invasion. This method seems to be useful for planning fractionated stereotactic radiation when used in addition to conventional imaging modalities that are often inconclusive in the SB region.
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Photographic Protocol for Image Acquisition in Craniofacial Microsomia
Craniofacial microsomia (CFM) is a congenital condition associated with orbital, mandibular, ear, nerve, and soft tissue anomalies. We present a standardized, two-dimensional, digitial photographic protocol designed to capture the common craniofacial features associated with CFM.
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Plasmacytoid myoepithelioma of minor salivary glands: report of case with emphasis in the immunohistochemical findings.
Myoepithelioma is a rare benign tumor of the salivary glands and is usually seen in the parotid gland and the minor salivary glands. It was once considered to be a type of pleomorphic adenoma (PA), but myoepitheliomas are today believed to be relatively aggressive tumors. Myoepitheliomas are most common in young adults between the ages of 30 and 50 and there are very few cases reported in individuals less than 18 years of age. We report a case of myoepithelioma located in the hard palate in a 15-year-old Brazilian male. The tumor was composed of plasmacytoid myoepithelial cells. An analysis of the immunohistochemical profile of the tumor cells showed positivity for vimentin, S-100 protein, and glial fibrillary acidic protein (GFAP), but not for smooth muscle actin (alpha-SMA) and cytokeratin 14 (CK14). We report this case because of the rarity of this tumor, especially in adolescents. We also discuss the histological parameters of the differential diagnosis of this tumor as well as its immunohistochemical profile.
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Effects of hypodontia on craniofacial structures and mandibular growth pattern
IntroductionThis study was performed to examine craniofacial structures in persons with hypodontia and to reveal any differences, that may occur, when agenetic teeth are only found in the maxilla, the mandible or in both jaws. The groups consistent of 50 children (33 girls, 17 boys) aged between 9 and 13.5 years were analyzed and assigned to three subgroups. Group 1 = upper jaw hypodontia. Group 2 = lower jaw hypodontia. Group 3 = hypodontia in both jaws.Materials and methodsEleven angular and three index measurements from lateral encephalographs and two linear measurements from dental blaster casts were calculated. All data was statistically analyzed, parameters with p < 5% were investigated for each subgroup respectively.
Results:
In comparison with standards the study group showed bimaxillary retrognathism and a reduction of the lower anterior facial height. Moreover both overbite and overjet significantly increased. Other values laid within the normal ranges. Evaluating results of the subgroups, differences in the means of SNA, SNB and overjet between the groups were observed.Analysis of the mandibular growth pattern revealed, that neither vertical nor horizontal patterns are dominant in hypodontia patients.
Conclusions:
In certain dentofacial parameters differences between persons with hypodontia and such with full dentition exist. According to our findings agenetic teeth may have a negative influence on the saggital development of a jaw and the lower face and may be responsible for increased overbites. This should receive attention in orthodontic treatment of hypodontia patients.
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Increase in periosteal angiogenesis through
heat shock conditioning
ObjectiveIt is widely known that stress conditioning can protect microcirculation and induce the release of vasoactive factors for a period of several hours. Little, however, is known about the long-term effects of stress conditioning on microcirculation, especially on the microcirculation of the periosteum of the calvaria. For this reason, we used intravital fluorescence microscopy to investigate the effects of heat shock priming on the microcirculation of the periosteum over a period of several days.
Methods:
Fifty-two Lewis rats were randomized into eight groups. Six groups underwent heat shock priming of the periosteum of the calvaria at 42.5°C, two of them (n = 8) for 15 minutes, two (n = 8) for 25 minutes and two (n = 8) for 35 minutes. After 24 hours, a periosteal chamber was implanted into the heads of the animals of one of each of the two groups mentioned above. Microcirculation and inflammatory responses were studied repeatedly over a period of 14 days using intravital fluorescence microscopy. The expression of heat shock protein (HSP) 70 was examined by immunohistochemistry in three further groups 24 hours after a 15-minute (n = 5), a 25-minute (n = 5) or a 35-minute (n = 5) heat shock treatment. Two groups that did not undergo priming were used as controls. One control group (n = 8) was investigated by intravital microscopy and the other (n = 5) by immunohistochemistry.
Results:
During the entire observation period of 14 days, the periosteal chambers revealed physiological microcirculation of the periosteum of the calvaria without perfusion failures. A significant (p < 0.05) and continuous increase in functional capillary density was noted from day 5 to day 14 after 25-minute heat shock priming. Whereas a 15-minute exposure did not lead to an increase in functional capillary density, 35-minute priming caused a significant but reversible perfusion failure in capillaries. Non-perfused capillaries in the 35-minute treatment group were reperfused by day 10. Immunohistochemistry demonstrated an increase in cytoprotective HSP70 expression in the periosteum after a 15-minute and a 35-minute heat shock pretreatment when compared with the control group. The level of HSP70 expression that was measured in the periosteum after 25 minutes of treatment was significantly higher than the levels observed after 15 or 35 minutes of heat shock exposure.
Conclusion:
A few days after heat shock priming over an appropriate period of time, a continuous increase in functional capillary density is seen in the periosteum of the calvaria. This increase in perfusion appears to be the result of the induction of angiogenesis.
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Reconstruction of defects of maxillary sinus wall after removal of a huge odontogenic lesion using prebended
3D titanium-mesh and CAD/CAM technique
- Methodology article -
A 63 year-old male with a huge odontogenic lesion of sinus maxillaris was treated with computer-assisted surgery. After resection of the odontogenic lesion, the sinus wall was reconstructed with a prebended 3D titanium-mesh using CAD/CAM technique. This work provides a new treatment device for maxillary reconstruction via rapid prototyping procedures.
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Piezoelectric-assisted removal of a benign fibrous histiocytoma of the mandible: An innovative technique for prevention of dentoalveolar nerve injury
In this article, we present our experience with a piezoelectric-assisted surgical device by resection of a benign fibrous histiocytoma of the mandible.A 41 year-old male was admitted to our hospital because of slowly progressive right buccal swelling. After further radiographic diagnosis surgical removal of the yellowish-white mass was performed. Histologic analysis showed proliferating histiocytic cells with foamy, granular cytoplasm and no signs of malignancy. The tumor was positive for CD68 and vimentin in immunohistochemical staining. Therefore the tumor was diagnosed as primary benign fibrous histio
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