• Gene for Vitamin D Metabolism Implicated in Multiple Sclerosis
• Prevalence of Knee Pain and Symptomatic Knee Osteoarthritis Rises
• Metabolic Syndrome in Obstructive Sleep Apnea
• PPIs and CAP, Revisited
• Acid Suppression Linked to Severe Clostridium difficile Infection
• Basis for Clinical Approval of Influenza Drugs Relenza and Tamiflu Questioned
• A New Four-Drug Regimen for H. pylori Infection?
• Add Parasites to the Causes of Postinfectious Irritable Bowel Syndrome!
• FDA Panelists Tied to Bayer
• Drug Approvals Hit a Seven-Year High in 2011
• 5% of Patients Account for Half of Healthcare Spending
• Vitamin D and UVB Radiation: How Much Is Necessary?
• Meta-Analysis Offers Advice on Monitoring During Lithium Therapy
• DSM-5 Set to Redefine Autism More Narrowly
• Autistic Children Have More Neurons
• FDA Approves Glucarpidase to Reduce Toxic Levels of Methotrexate
• Vitamin D May Aid Aging Eyes
MM: This landmark study may further explain the connection between not only MS bit other so called autoimmune diseases. Also, it shines more light on usable, potential treatments for MS that are economically and clinically appropriate.
Ann Neurol 2011 Dec; 70:881.
Gene for Vitamin D Metabolism Implicated in Multiple Sclerosis
Mutations that lead to altered vitamin D activation are identified as rare variants in familial MS.
To identify rare alleles associated with familial transmission of risk for multiple sclerosis (MS), investigators conducted genetic analyses in more than 12,000 people from a cohort of more than 30,000 families, including 43 families that had four or more individuals with MS.
By focusing on genetic regions associated with MS in a previous genome-wide association study, the researchers identified a single nucleotide polymorphism within the CYP27B1 gene that was present in all four individuals with MS from one genotyped family and was incompletely penetrant. Additional CYP27B1 mutations were found within 3046 trios of parents with an affected child and in 422 parent–affected sibling pairs.
The CYP27B1 mutation frequency was 0.9% in MS patients compared with 0.0% in 1873 healthy controls. CYP27B1 encodes the enzyme that converts 25-hydroxyvitamin D to biologically active vitamin D.
Comment: Whereas many sequencing studies involve finding major alleles by examining many individual cases, these investigators refined the search by focusing on strongly familial forms of MS. By identifying a rare mutation in a gene associated with vitamin D, this work contributes to understanding a potential mechanism underlying the associations between MS and serum vitamin D level (JW Neurol May 3 2011), ultraviolet exposure with latitude (JW Neurol Feb 7 2011), and late spring birth (BMJ 2005; 330:120). Trials of vitamin D supplementation in MS are now under way to determine whether this will alter relapse rates and magnetic resonance imaging lesions.
— Robert T. Naismith, MD Published in Journal Watch Neurology January 17, 2012
Citation(s): Ramagopalan SV et al. Rare variants in the CYP27B1 gene are associated with multiple sclerosis. Ann Neurol 2011 Dec; 70:881
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MM: That these researchers were unable to determine a statistical association between knee pain, obesity and an aging population seems almost ludicrous but figures do not lie. Is this only part of the picture? Could there be a dietary component attached to the increased incidence of osteoarthritis (OA) besides the rampant obesity that Americans suffer largely as a result of our Standard American Diet (SAD)? It certainly seems logical but we will undoubtedly need to look into this further. Although I am not a great proponent of “quick fixes” or “band-aid medicine”, we often times need just such a tool to deal with the here and now in order to simply live life. The problem that often arises is that the treatment may cause significant discomfort or additional problems to the patient being treated. For OA pain, Mark Drugs has a product that we have been recommending for almost a decade, All Flex Pro. This is a combination of half a dozen herbal and nutritional components that decrease inflammation and pain while causing no recorded side effects. Two (2) capsules, 2-3 times daily is the typical dose with no stomach upset and great results. Please call Mark Drugs (630)529-3400 or go to www.MarkDrugs.com for more information.
Ann Intern Med 2011 Dec 6; 155:725
Prevalence of Knee Pain and Symptomatic Knee Osteoarthritis Rises
Reports of knee pain are up and largely unexplained by age and weight.
An eightfold upsurge in knee replacements in recent decades has coincided with a growing obesity problem and an aging U.S. population. To evaluate whether age, obesity, and knee osteoarthritis (OA; defined radiologically with weight-bearing radiographs) are associated with temporal trends in knee pain and symptomatic OA (symptoms plus positive radiologic findings), researchers studied data from several thousand participants (age, 
60) in National Health and Nutrition Examination Surveys (NHANES; 1971–2004) and the Framingham Osteoarthritis Study (1983–2005).
After adjustments for age and body-mass index, the prevalence of knee pain in NHANES among non-Hispanic white or self-described Mexican American women increased from 13% in 1974 to 26% in 2004; rates for men increased from 9% to 20%. Similar trends were seen among self-described African Americans. In the Framingham cohorts, the prevalence of symptomatic knee OA rose from 10% to 17% among women and from 6% to 16% among men; however, the overall prevalence of radiologically defined knee OA did not rise.
Comment: The prevalence of knee pain has risen substantially during the past few decades, independent of age and body-mass index. Similarly, rates of symptomatic knee OA rose despite no change in the prevalence of radiologically defined OA. Whether these findings reflect an increase in non-OA causes of knee pain (e.g., meniscal injury, crystal disease), a lower threshold for patients to report pain, or other unidentified factors is unclear.
— Jamaluddin Moloo, MD, MPH Published in Journal Watch General Medicine January 17, 2012
Citation(s): Nguyen U-SDT et al. Increasing prevalence of knee pain and symptomatic knee osteoarthritis: Survey and cohort data. Ann Intern Med 2011 Dec 6; 155:725. (http://www.annals.org/content/155/11/725.full)
http://www.ncbi.nlm.nih.gov/pubmed/22147711?dopt=Abstract
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MM: There is no question in my mind that sleep apnea is a component of Metabolic Syndrome and that by improving sleep cycles other aspects of metabolic syndrome will improve. I think that it is ultimately necessary to address all aspects of this syndrome in order to show longitudinal beneficial results. Even better, life-changing results to maintain longitudinal motivation to establish lifelong life style changes are best.The big question, in the real world, is that people want a simple answer and they need visible results. In our practice, we have experienced that the approach that offers the greatest results and has the greatest success if weight loss and specificallt fat loss. We have found the most effective approach to this has been the HCG metabolic syndrome and weight maintenance program. Please call Mark Drugs (630)529-3400 or visit www.MarkDrugs.com for more information.
N Engl J Med 2011 Dec 15; 365:2277.
Metabolic Syndrome in Obstructive Sleep Apnea
Continuous positive airway pressure reversed metabolic syndrome in a small proportion of patients.
In patients with obstructive sleep apnea (OSA), continuous positive airway pressure (CPAP) can induce favorable changes in components of the metabolic syndrome. To quantitate these potential benefits, researchers in India conducted a double-blind, crossover trial: 86 patients with moderate-to-severe OSA received 3 months of CPAP and 3 months of sham CPAP, assigned in random order. Most participants were overweight middle-aged men. At baseline, 87% of participants met criteria for metabolic syndrome, but none were taking antihypertensive, lipid-lowering, or antidiabetic drugs.
Reversal of metabolic syndrome occurred in 11 patients during the CPAP phase, but in only 1 patient during the sham phase. Improvements in blood pressure, fasting glucose levels, and lipid levels were each responsible for several cases of metabolic syndrome reversal. However, in the study population overall, mean differences in these measurements between the CPAP and sham phases were modest –– a 4/2 mm Hg difference in systolic/diastolic blood pressure, a 10 mg/dL difference in LDL cholesterol levels, and no difference in HDL cholesterol levels, fasting glucose levels, or insulin resistance.
Comment: A relatively small proportion of patients experienced substantial improvement in cardiovascular risk factors after 3 months of CPAP. The most impressive result in this study was reduction in daytime sleepiness with CPAP –– an average decrease of 5 points in the 24-point Epworth Sleepiness Scale –– in contrast to no change with the sham intervention.
— Allan S. Brett, MD Published in Journal Watch General Medicine January 19, 2012
Citation(s):Sharma SK et al. CPAP for the metabolic syndrome in patients with obstructive sleep apnea. N Engl J Med 2011 Dec 15; 365:2277. (http://dx.doi.org/10.1056/NEJMoa1103944)
http://www.ncbi.nlm.nih.gov/pubmed/22168642?dopt=Abstract
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MM: Once again we see that PPI’s such as Prilosec, Nexium, Axid, etc., must be used cautiously if at all. But, what are the alternatives to chronic or even occasional GERD or reflux if one does not use these potentially detrimental products? Fortunately there is an alternative approach that has been shown to be clinically effective. Heart Burn AwayTM Chewable Tablets incorporates digestive enzymes, probiotics, stevia and the body’s own natural functions to combat GERD and provide relief. Please call Mark Drugs (630)529-3400 or visit us at www.MarkDrugs.com for more information.
Clin Infect Dis Clin Infect Dis 2012 Jan 1; 54:33
PPIs and CAP, Revisited
In a retrospective, nested case-control study, the risk for community-acquired pneumonia was 29% higher with current use of a proton-pump inhibitor than with past use.
Some researchers have postulated that, by facilitating bacterial colonization of the stomach and upper intestine, suppression of gastric acid increases the risk for community-acquired pneumonia (CAP). Proton-pump inhibitors (PPIs) are among the most potent suppressors of gastric-acid secretion and are commonly prescribed — often without clear indications. Attempts to prove an association between PPI exposure and CAP have yielded inconsistent results. Now, researchers have conducted a retrospective, nested case-control study to explore this issue further.
Analysis of linked pharmacy and administrative databases from the New England Veterans Healthcare System yielded 71,985 patients who were newly prescribed PPIs between October 1997 and September 2007. Within this group, 1544 patients developed CAP after PPI initiation. These case patients were matched by age and follow-up duration with 15,440 controls who received new PPI prescriptions during the same period but did not develop CAP. PPI use was categorized as current if the prescription end date was after the index CAP date and past if it preceded this date.
Cases were significantly more likely than controls to have one or more medical comorbidities (in addition to gastroesophageal reflux), to have been hospitalized 
90 days before the diagnosis of CAP, and to have been prescribed other medications possibly linked to CAP. The risk for developing CAP was higher in patients with current PPI use than in those with past use (adjusted odds ratio, 1.29; 95% confidence interval, 1.15–1.45). PPI prescription at a dose exceeding the standard daily dose (significantly more common in case patients than in controls) was also associated with CAP (P=0.012).
Comment: Because the study was retrospective and did not involve review of medical records, the results must be interpreted cautiously. However, the findings do suggest a modest effect of PPIs on the risk for CAP.
— Neil M. Ampel, MD Published in Journal Watch Infectious Diseases January 18, 2012
Citation(s):Hermos JA et al. Risk of community-acquired pneumonia in veteran patients to whom proton pump inhibitors were dispensed. Clin Infect Dis 2012 Jan 1; 54:33.
http://www.ncbi.nlm.nih.gov/pubmed/22100573?dopt=Abstract
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Clin Infect Dis 2011 Dec 15; 53:1173
Acid Suppression Linked to Severe Clostridium difficile Infection
Prescription use predicted both morbidity and mortality.
In several studies, acid suppression has been associated with risk for both Clostridium difficile infection (CDI) and recurrent infection (JW Gen Med Jun 8 2010 and JW Gen Med Oct 24 2006). Other studies have suggested a link between acid suppression and severity of disease.
Researchers reviewed 485 cases of laboratory-confirmed CDI among pediatric and adult patients at a single California medical center and associated outpatient clinics between 2004 and 2008. Of 47 patients with particularly severe CDI infections, 35 experienced complications (including intensive care unit admission), and 23 died. Patients receiving prescription proton-pump inhibitors, histamine-2 blockers, or both had nearly three times the risk for complications, compared with those who did not receive acid suppression; use of corticosteroids doubled risk. Multivariate analysis showed that both acid suppression and steroid use remained significant predictors of severe infection, as did age 
80 and hospital admission. In an analysis that was focused on mortality alone, only acid suppression and age 
80 were independent risk factors.
Comment: The biological plausibility of a link between acid suppression and CDI incidence and severity is strong, and the accumulating research is difficult to dismiss. Presumably, this study's findings could have been attenuated by widespread use of over-the-counter acid suppressants, but the results are enough in tune with other research that clinicians might reasonably discontinue acid suppressants in all proven or possible CDI patients who have no clear indications for continuing therapy.
— Abigail Zuger, MD Published in Journal Watch General Medicine January 17, 2012
Citation(s):Morrison RH et al. Risk factors associated with complications and mortality in patients with Clostridium difficile infection. Clin Infect Dis 2011 Dec 15; 53:1173. (http://dx.doi.org/10.1093/cid/cir668)
http://www.ncbi.nlm.nih.gov/pubmed/21976459?dopt=Abstract
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Basis for Clinical Approval of Influenza Drugs Relenza and Tamiflu Questioned
Patients may ask about a widely reported call from the Cochrane Collaboration for full disclosure of information about clinical studies leading to the approval of the neuraminidase inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza) used to treat influenza.
The reviewers point out that data on oseltamivir from 8 trials of a 10-trial meta-analysis remain unpublished and were not available either from the studies' authors or the manufacturer. That meta-analysis "has been the sole publication" cited by the CDC in support of its treatment guidelines.
On the basis of drug company data submitted to government agencies, the reviewers estimate that 60% of patient data from oseltamivir's phase III trials "have never been published." Using such "regulatory information" rather than published journal studies, the reviewers estimate that oseltamivir showed "no evidence of effect" on hospitalization rates; there was not enough information available to assess the drug's effects on complications or viral transmission.
Cochrane Collaboration Report (PDF):
http://click.jwatch.org/cts/click?q=227%3B67631003%3BVW9LkF%2FeZnnpYlMK%2Fv9qP
TimHT77mvbOBklZrNGu9l0%3D
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Am J Gastroenterol 2011 Nov; 106:1970
A New Four-Drug Regimen for H. pylori Infection?
Eradication was better than with standard triple therapy.
In developed countries, increasing antibiotic resistance has resulted in lower eradication rates for Helicobacter pylori. Thus, alternatives to the standard treatment regimens are badly needed. To evaluate a novel four-drug regimen, researchers at a U.S. medical center conducted an open-label, prospective, randomized trial involving 278 treatment-naive patients with H. pylori gastritis or peptic ulcer disease.
Patients received LOAD (levofloxacin, 250 mg at breakfast; omeprazole, 40 mg before breakfast; nitazoxanide 500 mg twice daily with meals; doxycycline, 100 mg at dinner) for 7 or 10 days or LAC (lansoprazole 30 mg; amoxicillin 1 g twice daily at breakfast and dinner; clarithromycin 500 mg, twice daily at breakfast and dinner) for 10 days. A 6-week washout period for any antibiotics or proton-pump inhibitors (PPIs) preceded the treatment. H. pylori eradication was determined by stool testing done at least 4 weeks after the end of treatment.
Eradication rates in the intent-to-treat population were 88.9% for 10-day LOAD, 90.0% for 7-day LOAD, and 73.3% for LAC. Both LOAD therapies were statistically superior to LAC. Adverse events were similar between LOAD and LAC recipients. The authors concluded that LOAD therapy is potentially more efficacious than the current standard of care for H. pylori gastritis and ulcers in treatment-naive patients.
Comment: Multiple new approaches are being evaluated to increase H. pylori eradication rates. To date, the 90% minimally acceptable cure rate established internationally has been achieved only in trials of bismuth-based quadruple therapy in the U.S. and Europe. Yet, sequential therapy has been effective in some studies (JW Gastroenterol Jan 13 2012). The present findings suggest that a combination involving three antibiotics and a PPI is superior to standard triple therapy. Quadruple-drug therapy has the disadvantages of being more expensive, which is particularly problematic for patients in developing countries, and of more-complicated dosing, which could lead to decreased compliance. Such a regimen might have a therapeutic role in developed countries, however, and merits additional studies in broader populations.
— David J. Bjorkman, MD, MSPH (HSA), SM (Epid.) Published in Journal Watch Gastroenterology January 13, 2012
Citation(s):Basu PP et al. A randomized study comparing levofloxacin, omeprazole, nitazoxanide, and doxycycline versus triple therapy for the eradication of Helicobacter pylori. Am J Gastroenterol 2011 Nov; 106:1970
http://www.ncbi.nlm.nih.gov/pubmed/21989146?dopt=Abstract
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Gut 2012 Feb; 61:214
Add Parasites to the Causes of Postinfectious Irritable Bowel Syndrome!
IBS and chronic fatigue were more common in patients who had previously contracted giardiasis than in population controls.
After a bout of infectious gastroenteritis, some patients develop irritable bowel syndrome (IBS), which can persist for years. Now, researchers have examined the prevalence of postinfectious IBS and chronic fatigue among patients who had contracted giardiasis during an outbreak in Norway.
Three years after the outbreak, questionnaires were sent to 1252 patients with verified Giardia lamblia infection and 3598 matched controls from the general population; responses were received from 65% and 31% of these two groups, respectively.
IBS was reported in a higher percentage of giardiasis patients than controls (46% vs. 14%; adjusted relative risk, 3.4), as was chronic fatigue (46% vs. 12%; ARR, 4.0), and the combination of IBS and chronic fatigue (29% vs. 5%; ARR, 6.8).
Comment: The mechanisms by which giardiasis and other infections can induce chronic illnesses that persist after apparent eradication of the infection are unclear. Nonetheless, this study reinforces evolving concepts about postinfectious irritable bowel syndrome and other long-term complications that develop after acute gastroenteritis.
— Douglas K. Rex, MD Published in Journal Watch Gastroenterology January 13, 2012
Citation(s):Wensaas K-A et al. Irritable bowel syndrome and chronic fatigue 3 years after acute giardiasis: Historic cohort study. Gut 2012 Feb; 61:214.
http://www.ncbi.nlm.nih.gov/pubmed/21911849?dopt=Abstract
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FDA Panelists Tied to Bayer
FDA advisers recently voted that the benefits of four popular Bayer AG birth-control products (Yaz, Yasmin, Bevaz, Safyral) outweigh the blood-clot risk. What was not disclosed was that three of the advisers have been tied to Bayer, serving as consultants, speakers, or researchers. The committee vote was 15 to 11 that the benefits outweighed the risks.
http://online.wsj.com/article/SB10001424052970203436904577153160177537828.html?mod
=dist_smartbrief
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Drug Approvals Hit a Seven-Year High in 2011
The FDA has approved 30 new treatments in 2011 compared with 21 last year. The new approvals may help the drug companies overcome a rash of patent expirations. At least 21 medicines will lose a combined $11.5 billion in revenue as a result of patent expirations in 2012, and they will generate more than $4 billion in 2012 from products that were introduced in 2010 and 2011.
http://www.bloomberg.com/news/2012-01-05/drug-approvals-in-u-s-reached-a-seven-year-high-in-2011-on-improved-data.html
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5% of Patients Account for Half of Healthcare Spending
According to a recent federal report, 1% of Americans accounted for 22% of healthcare costs in 2009 (about $90,000 a person), and 5% accounted for 50% of healthcare costs, about $36,000 each, the report said. The report may be used to predict which consumers are most likely to drive up healthcare costs and determine the best ways to save money.
http://www.pharmacynewsflash.com/opha/Story.nsp?story_id=167877595
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Br J Dermatol 2011 Oct 20
Vitamin D and UVB Radiation: How Much Is Necessary?
For individuals unable to benefit from supplements, ultraviolet B exposure every 2 weeks may be an alternative.
Adequate vitamin D levels are necessary for bone health and might prevent a variety of other diseases. Many individuals are able to maintain adequate circulating concentrations of this important molecule during the summer, when ambient ultraviolet B (UVB) from sunlight is greatest. However, during winter months, when terrestrial UVB is at its nadir, levels can drop precipitously, particularly in regions far from the equator. For most, vitamin D deficiency can be addressed by the administration of supplements. However, physician-monitored UVB treatments have been advocated as an alternative therapeutic approach (see JW Dermatol May 7 2010).
Investigators in Denmark assessed how much artificial UVB is necessary to maintain summertime vitamin D concentrations. Every 1, 2, or 4 weeks during a 16-week period between October and February, 55 subjects received one standard erythemal dose (equivalent to 10 minutes of summer noonday sun exposure) to about 88% of total body area from a broadband UVB light source; a control group received no UVB.
UVB administered every 2 weeks was sufficient to maintain summertime vitamin D levels. Smaller changes were observed in those with higher concentrations at baseline and in older subjects, and greater changes were seen in those with higher body mass index and total body surface area.
Comment: For individuals resistant to or unable to take supplements, ultraviolet B exposure every 2 weeks may be an alternative method for maintaining summertime levels of vitamin D in winter. Narrowband UVB might be a better choice than the broadband UVB used in this study, because it may have fewer long-term adverse effects. It is important to emphasize that tanning beds do not emit the appropriate wavelengths and have been linked to melanoma and nonmelanoma skin cancers. Increasing UV exposure is not necessarily healthier; higher baseline vitamin D levels correlated with smaller increases in vitamin D concentrations.
— Craig A. Elmets, MD Published in Journal Watch Dermatology January 13, 2012
Citation(s):Bogh MKB et al. A small suberythemal UVB dose every second week is sufficient to maintain summer vitamin D levels: A randomized controlled trial. Br J Dermatol 2011 Oct 20; [e-pub ahead of print]. (http://dx.doi.org/10.1111/j.1365-2133.2011.10697.x).
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Meta-Analysis Offers Advice on Monitoring During Lithium Therapy
Lithium's side effects should prompt regular clinical monitoring, but a meta-analysis in the Lancet "reaffirms its role as a treatment of choice for bipolar disorder," according to commentators.
Researchers examined some 385 studies, ranging from randomized controlled trials to case reports, to measure lithium's effects on renal, thyroid, and parathyroid function, weight gain, hair and skin disorders, and teratogenicity. Among the findings:
- Lithium's effects on glomerular filtration rates and urinary concentrating ability were small; data on renal failure were scarce, but the absolute risk was small.
- The rate of hypothyroidism was increased.
- Blood calcium levels and hyperparathyroidism were also increased with lithium.
- There was no increased risk for congenital malformations.
The authors recommend monitoring calcium levels before therapy and assessing renal and thyroid function and calcium levels annually. Regarding pregnancy, clinicians should counsel women about the uncertainty surrounding lithium and birth defects, taking into account the risks for mood instability if treatment is withdrawn.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61516-X/abstract
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DSM-5 Set to Redefine Autism More Narrowly
A new definition of autism, apparently under review for the next edition of the Diagnostic and Statistical Manual of Mental Disorders, could exclude many now diagnosed as having the condition, the New York Times reports.
The new criteria would consolidate three diagnoses — autism, Asperger syndrome, and pervasive developmental disorder, not otherwise specified — into a single category, autism spectrum disorder. To qualify for that new diagnosis, a person would have to show three deficits in social interaction and communication and at least two repetitive behaviors.
According to the Times report, an analysis using the new criteria estimated that under half of those currently diagnosed (and thus eligible for a range of social support services) would qualify.
Asked to comment, Dr. Peter Roy-Byrne, editor-in-chief of Journal Watch Psychiatry wrote: "This move will reduce the number of people in the category and confine the category to the most severe cases. But those left behind will still have disabling problems."
http://www.nytimes.com/2012/01/20/health/research/new-autism-definition-would-exclude-many-study-suggests.html?_r=1
http://www.dsm5.org/Pages/Default.aspx
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JAMA 2011 Nov 9; 306:2001
Autistic Children Have More Neurons
These findings support the hypothesis that autism is present at birth, even if not yet clinically evident.
Autistic children have macrocephaly (e.g., Neurology 2002; 59:175), but whether neuron and glia cell counts correspond with that finding has not been known. These researchers conducted a postmortem study of seven autistic boys and six normal boys (age range, 2–16 years). Dorsolateral and mesial prefrontal cortical (DLPFC and mPFC, respectively) areas in the brain specimens were suitable for stereological cell counts. Causes of death could not include diseases or conditions associated with increased brain size or neuronal cell counts. Autism severity ranged from intellectual disability to having functional speech, ascertained by postmortem standardized parent interviews (1 child was diagnosed with autism when alive). Analyses compared neuron and glia cell counts and brain weights between groups.
Mean neuron cell counts in the DLPFC and mPFC were 67% higher in the autism group (DLPFC, 79%; mPFC, 29%) than in the healthy comparison group. Compared with mean normal brain weights for age, brain weights were 17.6% higher in the autism group (a significant difference) and 0.2% higher in the comparison group. Only in controls were cell counts linearly associated with brain weight. Glia cell counts did not differ significantly between groups.
Comment: Because neuronal development is ordinarily complete in the first half of gestation, these findings support the hypothesis that autism is present at birth, even if not yet clinically evident. Therefore, they reinforce the need for the earliest possible interventions that might mitigate later impairments (JW Psychiatry Jun 21 2010) and for preventive efforts as environmental risk factors become known (JW Psychiatry Aug 15 2011 and Aug 29 2011). Future researchers can address how these findings relate to different clinical trajectories (worsening, regression, lack of development; JW Psychiatry Jun 27 2011).
— Barbara Geller, MD Published in Journal Watch Psychiatry December 5, 2011
Citation(s):Courchesne E et al. Neuron number and size in prefrontal cortex of children with autism. JAMA 2011 Nov 9; 306:2001.
http://www.ncbi.nlm.nih.gov/pubmed/22068992?dopt=Abstract
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FDA Approves Glucarpidase to Reduce Toxic Levels of Methotrexate
The FDA has approved glucarpidase (marketed as Voraxaze) to lower toxic levels of methotrexate related to kidney failure. Cancer patients may develop kidney failure when treated with high doses of methotrexate.
In a study of 22 patients receiving glucarpidase, 10 patients had methotrexate levels fall below a critical level within 15 minutes and stay low for 8 days. The drug eliminated 95% of methotrexate in all patients.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm287997.htm
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http://www.imakenews.com/eletra/mod_print_view.cfm?this_id=2328784&u=
&show_issue_date=F&issue_id=000569116&lid=bkyhh8n&uid=b1h1R7NC
Vitamin D May Aid Aging Eyes
Findings in mice hold implications for other degenerative conditions, such as Alzheimer’s and cardiovascular disease
by Craig Weatherby
Could salmon, sardines, tuna, and other fatty fish be good for aging eyes? And might sunlight – which in excess can damage eyes – have a vision-guarding upside in moderation? British researchers report that vitamin D – which abounds only in fatty fish, supplements, and (indirectly) in sunlight – reduced the effects of aging in mouse eyes, and improved the vision of older mice significantly. They expressed the hope that vitamin D supplements might help prevent or ameliorate age-related human eye diseases … especially age-related macular degeneration (AMD), which is the leading cause of blindness in people over 50 in the developed world. The research was carried out by a team from the Institute of Ophthalmology at University College London (Lee V et al. 2012).
Professor Glen Jeffery, who led the work, explained the basics behind the problem and their results:
“Cells in the retina detect light as it comes into the eyes and then send messages to the brain, which is how we see. The retina actually requires proportionally more energy than any other tissue in the body, so it has to have a good supply of blood. However, with ageing the high energy demand produces debris and there is progressive inflammation even in normal animals. In humans this can result in a decline of up to 30% in the numbers of light receptive cells in the eye by the time we are 70 and so lead to poorer vision.” (BBSRC 2012)
Vitamin D boosted rodent’s vision by cutting retinal debris and inflammation
The researchers found that when old mice were given vitamin D for just six weeks, inflammation was reduced, the debris partially removed, and tests showed that their vision was improved (Lee V et al. 2012).
The researchers identified two changes taking place in the eyes of the mice that they think accounted for this improvement:
- A damaging excess of immune-system cells called macrophages was cut considerably in the eyes of the mice given vitamin D, which also triggered the remaining macrophages to change to a different configuration, in which they curbed inflammation and cleared up debris.
- Mice given vitamin D enjoyed a reduction in deposits of a toxic protein called amyloid beta that accumulates with age. Inflammation and the accumulated amyloid beta contribute, in humans, to an increased risk of age-related macular degeneration (AMD).
Likewise, a recent study from Duke University Medical Center showed that clearing amyloid deposits from rodent’s eyes (using antibodies) helped heal the animals’ retinas (Ding JD et al. 2011). Based on their findings in mice, the Brits think that giving vitamin D supplements to people who are at risk of AMD might help prevent the disease. According to Professor Jeffery, their results hold implication for other degenerative conditions, such as Alzheimer’s and cardiovascular disease:
“People might have heard of amyloid beta as being linked to Alzheimer's disease and new evidence suggests that vitamin D could have a role in reducing its build up in the brain. So, when we saw this effect in the eyes as well, we immediately wondered where else these deposits might be being reduced.” (BBSRC 2012)
Indeed, when Dr. Jeffery’s team examined the blood vessels of mice given vitamin D supplements, those animals had significantly less amyloid beta built up in their blood vessels, including in the critical aorta, compared with the control mice. As he said, “Finding that amyloid deposits were reduced in the blood vessels of mice that had been given vitamin D supplements suggests that vitamin D could be useful in helping to prevent a range of age-related health problems, from deteriorating vision to heart disease.” (BBSRC 2012).
Professor Jeffery thinks that this link between vitamin D and a range of age-related diseases might be linked to our evolutionary history. For much of human history our ancestors lived in Africa, probably without clothes, and so were exposed to strong sunlight all year round. This would have triggered vitamin D production in the skin. Humans have only moved to less sunny parts of the world and adopted clothing relatively recently and so might not be well adapted to reduced exposure to the sun. Secondly, life expectancy in the developed world has increased greatly over the past few centuries, so reduced exposure to vitamin D is now coupled with exceptionally long lifespans.
Dr. Jeffery expressed cautious optimism about his team’s results:
“Researchers need to run full clinical trials in humans before we can say confidently that older people should start taking vitamin D supplements, but there is growing evidence that many of us in the Western world are deficient in vitamin D and this could be having significant health implications.” (BBSRC 2012)
Professor Douglas Kell, BBSRC Chief Executive, made an important point, saying, “Many people are living to an unprecedented old age in the developed world. If we are to have any hope of ensuring that more people can enjoy a healthy, productive retirement then we must learn more about the changes that take place as animals age. By studying the fundamental biology of one organ scientists can begin to draw links between a number of diseases in the hope of developing preventive strategies.” (BBSRC 2012).
You can say that again, old chap.
Sources: Biotechnology and Biological Sciences Research Council (BBSRC). Vitamin D could combat the effects of ageing in eyes. January 16, 2012. Accessed at http://www.bbsrc.ac.uk/news/health/2012/120116-pr-vit-d-combat-ageing-in-eyes.aspx. ; Ding JD, Johnson LV, Herrmann R, Farsiu S, Smith SG, Groelle M, Mace BE, Sullivan P, Jamison JA, Kelly U, Harrabi O, Bollini SS, Dilley J, Kobayashi D, Kuang B, Li W, Pons J, Lin JC, Bowes Rickman C. Anti-amyloid therapy protects against retinal pigmented epithelium damage and vision loss in a model of age-related macular degeneration. Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):E279-87. Epub 2011 Jun 20.; Hoh Kam J, Lenassi E, Jeffery G. Viewing ageing eyes: diverse sites of amyloid Beta accumulation in the ageing mouse retina and the up-regulation of macrophages. PLoS One. 2010 Oct 1;5(10). pii: e13127.; Johnson LV, Leitner WP, Rivest AJ, Staples MK, Radeke MJ, Anderson DH. The Alzheimer's A beta -peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration. Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11830-5. Epub 2002 Aug 20.; Lee V, Rekhi E, Kam JH, Jeffery G. Vitamin D rejuvenates aging eyes by reducing inflammation, clearing amyloid beta and improving visual function. Neurobiol Aging. 2012 Jan 2. [Epub ahead of print]
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