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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
October 15, 2011

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Cialis Approved for Benign Prostatic Hyperplasia
NSAID Use Can Decrease Hemoglobin Level
Sublingual Tablets Alleviate Grass Allergy Symptoms
More Data on Hormone Therapy and the Timing Hypothesis
Healthier Maternal Diet Linked to Lower Risk for Certain Birth Defects in Offspring
Prolonged Bottle Use Is Associated with Increased Risk for Childhood Obesity
Polycystic Ovary Syndrome Linked to Adverse Pregnancy Outcomes, Regardless of
   Fertility Treatment
FDA Approves First Combination Drug to Treat Type 2 Diabetes and High Cholesterol
Inhaled Corticosteroids Raise Fracture Risk in COPD Patients
Drug Resellers Marking up Short-supply Medications 80-fold Being Probed
PHARMA Spent $4.7M on Lobbying in Second Quarter 2011
Last Tax Holiday Shows U.S. Firms Cut Thousands of Jobs
Time Trends for Mortality Among Patients with Early- vs. Late-Onset Type 1 Diabetes
Depression Is Less Common in Women Who Drink Coffee
Relation Between Barrett's Esophagus and Adenocarcinoma Questioned
Research finds that spices may reduce insulin, triglyceride response
Studies have found cherries to be an inexpensive natural pain
Food for Thought: The Effects of Race, Ancestry, and Environment on Food Allergies
Vitamin E Associated with Increased Prostate Cancer Risk
Folic Acid Use Early in Pregnancy Might Protect Against Language Delay in Offspring
Another Helping of Flaxseed for Breast Cancer?
Women with Restless Legs Syndrome More Likely to Have Hypertension
Coronary Disease Prevalence Declines in Most Areas of the U.S.
No Association Found Between Urinary BPA and Type 2 Diabetes
α-Lipoic Acid Is Ineffective for Diabetic Neuropathy
Intrauterine Devices Might Prevent More Than Pregnancy
Estradiol Vaginal Ring vs. Oral Oxybutynin for Overactive Bladder
Key Obstetric Risk Factors for Cerebral Palsy
Vitamin D Fights TB
Erectile Function After Prostate Cancer Therapy
Why Was the 1918 Influenza Pandemic So Lethal?
Omega-3s Deemed Helpful in ADHD
Cancer Patients Lacked Vitamin D
Breast Cancer in Women Younger Than 25

MM: Talk about marketing opportunities. Insurance coverage of ED drugs is typically very limited. Imagine an opportunity to dominate a market through outside support. Let’s wait and see how the insurance industry follows up on this one.
Cialis Approved for Benign Prostatic Hyperplasia
     The erectile dysfunction drug tadalafil (Cialis) has been approved to treat benign prostatic hyperplasia, either alone or when it occurs along with erectile dysfunction, the FDA announced on Thursday.
     Approval was based on two trials in which men taking 5 mg daily of tadalafil had significant improvements in BPH symptoms compared with those taking placebo. A third placebo-controlled trial showed that the drug simultaneously improved symptoms of both BPH and erectile dysfunction.
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Aliment Pharmacol Ther 2011 Oct; 34:808
NSAID Use Can Decrease Hemoglobin Level
Data summarized from two separate randomized trials showed drops of ≥2 g/dL in hemoglobin in celecoxib and diclofenac users.
     Upper gastrointestinal (GI) bleeding is a common complication of using nonsteroidal anti-inflammatory drugs (NSAIDs). This risk can be reduced by using a selective NSAID such as cyclooxygenase (COX)-2 inhibitors (coxibs) or by using cotherapy with a proton-pump inhibitor (PPI). However, the effects of NSAIDs are not limited to the upper GI tract but can also result in increased intestinal permeability, intestinal ulcerations, and blood loss by other mechanisms.
     To examine the effects of NSAIDs on total intestinal blood loss, researchers conducted an industry-funded investigation of whether hemoglobin (Hb) levels decreased by ≥2 g/dL in patients who took diclofenac or celecoxib in two previous large randomized trials, CLASS (JAMA 2000; 284:1247) and CONDOR (Lancet 2010; 376:173). After 6 months, a small percentage of patients in each trial who received these NSAIDs experienced a drop in Hb of 2 g/dL. These decreases in Hb occurred more often in diclofenac recipients than celecoxib recipients (3.3% vs. 1.9% in the CLASS trial, and 5.7% vs. 2.0% in the CONDOR trial).
     Comment: The authors conclude that meaningful decreases in hemoglobin occur in patients taking NSAIDs over time. Although the recognition of a drop in Hb with NSAID therapy is not novel, the authors emphasize that the finding is persistent despite differences in the two trial designs (e.g., inclusion of participants with Helicobacter pylori virus infection and users of low-dose aspirin in CLASS but not CONDOR), and, therefore, implies a clinically significant NSAID effect that warrants future investigation.
David J. Bjorkman, MD, MSPH (HSA), SM (Epid.) Published in Journal Watch Gastroenterology October 7, 2011
     Citation(s): Goldstein JL et al. Haemoglobin decreases in NSAID users over time: An analysis of two large outcome trials. Aliment Pharmacol Ther 2011 Oct; 34:808. (http://dx.doi.org/10.1111/j.1365-2036.2011.04790.x)
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J Allergy Clin Immunol 2011 Sep; 128:559
Sublingual Tablets Alleviate Grass Allergy Symptoms
Will a grass-pollen tablet lessen the need for allergy shots?
     Allergic rhinitis affects nearly one quarter of people in westernized countries. Treatment consists of allergen avoidance, pharmacotherapy, and specific subcutaneous immunotherapy (SCIT). Only SCIT has a disease-modifying effect, but it carries the burden of several years of injections and possible systemic reactions. The regulatory agencies in several European countries have approved sublingual immunotherapy (SLIT) preparations, including a freeze-dried 5-grass-pollen tablet (Oralair).
     In an industry-sponsored, randomized study, 633 European patients were treated for 3 years with placebo or SLIT therapy starting either 2 months before or 4 months before — and continuing through — the grass-pollen season. Mean symptom scores in the active-treatment group began improving during the first year and were 36% better than placebo scores at year 3; no additional benefit was noted for 4-month (compared with 2-month) preseason administration.
     Comment: Oralair likely will be the first FDA-approved SLIT product, perhaps to be followed by products containing ragweed and dust mite extracts. Systemic reactions are very rare, so therapy can be given at home — and for only about 5 months annually. Several questions about SLIT likely will be answered with long-term widespread use: Is it as effective, and will it convey the same long-lasting disease-modifying effect of SCIT? Will it be marketed to primary care physicians? Will U.S. allergists embrace it, given the potential loss of revenue when SLIT replaces in-office allergy shots?
     — David J. Amrol, MD Dr. Amrol is an Associate Professor of Clinical Internal Medicine and Director of the Division of Allergy and Immunology at the University of South Carolina School of Medicine in Columbia.
     Published in Journal Watch General Medicine September 27, 2011
     Citation(s): Didier A et al. Sustained 3-year efficacy of pre- and coseasonal 5-grass-pollen sublingual immunotherapy tablets in patients with grass pollen–induced rhinoconjunctivitis. J Allergy Clin Immunol 2011 Sep; 128:559. (http://dx.doi.org/10.1016/j.jaci.2011.06.022)
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MM: This data is no surprise. I have been saying for years that it’s not just the right hormone, but the right hormone and amount for the individual patient. There are many benefits to BHRT (Bio-Identical Hormone Replacement Therapy) but it’s important that the BHRT is right for the individual. Mark Drugs has worked with men, women and their doctors to design and deliver the right combination to get the greatest possible benefits from BHRT with the least amount of risk. Please contact us for more information or for a clinician referral to guide and treat your unique needs.
Menopause 2011 Sep; 18:943.
More Data on Hormone Therapy and the Timing Hypothesis
Results of an angiogram-based study reinforce the theory that HT use by recently menopausal women prevents coronary artery disease.
     Recent reports (JW Womens Health Mar 31 2011 and JW Womens Health Apr 5 2011) have strengthened the hypothesis that use of hormone therapy (HT) by recently menopausal women can prevent coronary artery disease (CAD). Now, in a study of 654 women (83% white) who underwent coronary angiography for suspected cardiac ischemia, investigators assessed prevalent CAD and then followed participants for cardiovascular disease (CVD) events for a median of 6 years to evaluate associations between HT use and CAD. Overall, 20% of participants had undergone surgical menopause and 44% were current HT users (75% estrogen-only HT).
     Mean age was 66 in the 167 women with CAD at baseline and 61 in the 487 women without prevalent CAD. Compared with never users, ever users of HT were 60% less likely to have prevalent CAD (P<0.0001), and current HT users were 50% less likely to have CAD (P=0.0007). Among 509 women who experienced natural menopause, those who initiated HT before age 55 had significantly milder CAD severity than did HT never users (P<0.0001). In contrast, CAD severity in naturally menopausal women who initiated HT at age ≥55 did not differ from that in never users. Such differences in CAD severity were not noted for surgically menopausal women. Prospective analysis revealed a trend toward lower incidence of CVD events in ever users with natural menopause (hazard ratio, 0.72; P<0.08) but not in those with surgical menopause.
     Comment: Menopausal women who undergo evaluation with coronary angiography certainly do not represent the overall population — and the observational nature of this report does not allow causality to be determined. Furthermore, the small number of surgically menopausal women who did not use hormone therapy limited statistical power for analyses of this subgroup. Nonetheless, these findings add further support to the premise that HT is safe when prescribed to recently menopausal women with bothersome vasomotor symptoms or other indications.
Andrew M. Kaunitz, MD Published in Journal Watch Women's Health October 6, 2011
     Citation(s): Shufelt CL et al. Timing of hormone therapy, type of menopause, and coronary disease in women: Data from the National Heart, Lung, and Blood Institute–sponsored Women's Ischemia Syndrome Evaluation. Menopause 2011 Sep; 18:943.
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Healthier Maternal Diet Linked to Lower Risk for Certain Birth Defects
in Offspring

Neural tube defects and orofacial clefts are less common among the offspring of women who follow a healthy diet before pregnancy, according to a case-control study in the Archives of Pediatrics and Adolescent Medicine.
     Some 3400 women with pregnancies marked by anencephaly, spina bifida, cleft lip, or cleft palate, and 6100 women who had infants without birth defects, completed postnatal questionnaires about their dietary habits in the year before they became pregnant. The women's diets were then scored according to how closely they mirrored a Mediterranean diet or a diet based on the USDA's food pyramid.
     Overall, the highest quartile score for either type of diet was significantly associated with reduced risks for birth defects, compared with the lowest quartile. In particular, the highest food pyramid scores were associated with about a 50% reduction in anencephaly risk and 35% reduction in cleft palate risk, while the highest Mediterranean diet scores conferred reductions of 35% and 25%, respectively.
Editorialists conclude that the study's lesson "is an important one: people, including women of childbearing age, should eat good food."
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J Pediatr 2011 Sep; 159:431
Prolonged Bottle Use Is Associated with Increased Risk for Childhood Obesity
Bottle use at 24 months predicted body-mass index ≥95th percentile at age 5.5 years.
     An early intervention for prevention of obesity is badly needed. Investigators reviewed longitudinal data from a national birth cohort of 6750 children born in 2001 to determine if bottle use at 24 months was associated with obesity (BMI >95th percentile) at age 5.5 years. Overall, 22% of the children were bottle users at 24 months (18.9% at bedtime and 10.5% during the day), and 17% were obese at 5.5 years.
     Obesity prevalence was higher in children who used bottles at 24 months than in children who did not use them at 24 months (23% vs. 16%). When adjusted for multiple confounding variables, risk for obesity was 1.3 times higher for prolonged bottle users (95% confidence interval, 1.05–1.68) than for non–bottle users at 24 months. No significant differences were found in risk for obesity between daytime and bedtime bottle users. The association between obesity and prolonged bottle use was not affected by weight at 9 months or maternal obesity.
     Comment: These results suggest that prolonged bottle use might be a modifiable risk factor for early obesity and that parents should be advised to avoid bottle use in children after age 12 months, especially children for whom we have concerns for overweight. Early experience with a cup, which can begin in most infants at age 6 months, will enhance later weaning from the breast or bottle. In addition, parents should be encouraged to use bedtime soothing methods other than nursing or drinking milk from a bottle.
F. Bruder Stapleton, MD, and Martin T. Stein, MD Published in Journal Watch Pediatrics and Adolescent Medicine October 5, 2011
     Citation(s):Gooze RA et al. Prolonged bottle use and obesity at 5.5 years of age in US Children. J Pediatr 2011 Sep; 159:431.
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Polycystic Ovary Syndrome Linked to Adverse Pregnancy Outcomes,
Regardless of Fertility Treatment

     Women with polycystic ovary syndrome (PCOS) face increased risk for adverse pregnancy and neonatal outcomes, regardless of whether they've undergone assisted reproductive technology, a BMJ study finds.
     Using Sweden's national birth register, researchers compared outcomes in some 3800 singleton births in which the mother had PCOS and nearly 1.2 million in which the mother did not. After adjustment for maternal age, BMI, and use of assisted reproductive technology, women with PCOS were significantly more likely to experience gestational diabetes (odds ratio, 2.3), preeclampsia (OR, 1.5), cesarean delivery (OR, 1.2), and preterm birth. They were also more likely to give birth to babies who were large for gestational age, aspirated meconium, and had low Apgar scores.
     An editorialist writes: "The clinical implications are clear. Pregnant women with polycystic ovary syndrome should be considered at increased risk of perinatal complications, should be monitored accordingly, and should have their babies delivered in hospital."
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MM: Ok, its time to rant. How can a drug that has been shown to increase the risk of diabetes at higher doses be allowed to be included in a diabetes lowering combination? This makes NO SENSE!! Again, we see who is paying the bills and who is responding to a paycheck at the FDA
FDA Approves First Combination Drug to Treat Type 2 Diabetes and
High Cholesterol

     A sitagliptin–simvastatin drug combination (brand name, Juvisync) has been approved for treating adults with both type 2 diabetes and high cholesterol, the FDA announced late last week.
     The fixed-dose tablet has been approved in three different strengths: 100 mg sitagliptin/10 mg simvastatin, 100 mg/20 mg, and 100 mg/40 mg. Availability of tablets with 50-mg sitagliptin is pending; in the meantime, patients who require this dose should continue taking the single-ingredient pill.
     The FDA noted that it has "recently become aware" of a small risk that statins can increase blood sugar levels in patients with type 2 diabetes. Accordingly, Juvisync's prescribing information will warn about this potential adverse reaction. In addition, patients will receive a medication guide when filling their prescriptions.
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Thorax 2011 Aug; 66:699
Inhaled Corticosteroids Raise Fracture Risk in COPD Patients
Results should not deter ICS use in patients with moderate-to-severe chronic obstructive pulmonary disease.
     Patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) often are treated with inhaled corticosteroids (ICS) to decrease the frequency of exacerbations. Systemic absorption clearly occurs at high doses, but whether such absorption results in lower bone density and elevated fracture risk remains unclear.
     A meta-analysis of 16 randomized controlled trials (RCTs) involved 9143 ICS users and 8370 controls; fluticasone or budesonide were used in all but one of the RCTs. Most patients had severe COPD, and older men predominated. All studies included long-term follow-up (mean duration, 90 weeks), but individual studies varied widely. Fracture risk rose significantly with ICS use — 180 fractures occurred in ICS recipients, and 141 occurred in controls (odds ratio, 1.27; P=0.04). None of the RCTs was actually designed to look at bone density or fractures, and the data were largely from unpublished company reports. The authors also analyzed seven controlled observational studies that involved 69,000 patients and found a similar rise in fracture risk with ICS (OR, 1.21; P<0.001).
     Comment: This meta-analysis strongly suggests an elevated risk for fracture with ICS use. The study does not clearly define a dose or duration of use that puts a patient at risk. Providers should not be deterred from adding ICS to long-acting bronchodilators in patients with moderate-to-severe COPD and frequent flares but should use caution in prescribing these medications for patients with milder disease, rare exacerbations, or elevated fracture risk.
Patricia Kritek, MD Published in Journal Watch General Medicine September 13, 2011
     Citation(s):Loke YK et al. Risk of fractures with inhaled corticosteroids in COPD: Systematic review and meta-analysis of randomised controlled trials and observational studies. Thorax 2011 Aug; 66:699. (http://dx.doi.org/10.1136/thx.2011.160028)
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MM: In this time of drug shortages Mark Derugs is stepping up. We are able to make many of these medications that are in short supply for physicians and hospitals at very reasonable prices. Call us for more information.
Drug Resellers Marking up Short-supply Medications 80-fold Being Probed
     With the number of drug shortages tripling in the past five years, gray-market companies that buy up critical drugs in short supply and resell them to hospitals and pharmacies at a markup of as much as 80 times their price are under investigation.
     Representative Elijah Cummings (Democrat, Maryland) has launched the investigation as the U.S. faces record drug shortages. Some hospitals have changed medical practices and in some cases, use less-effective medicines. Cummings said one reseller charged a hospital 80 times the typical price for cytarabine.
     "Price gouging for drugs that treat cancer in children is simply unconscionable," said Cummings; "We want to know where these companies are getting these drugs, and how much they are making in profits."
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PHARMA Spent $4.7M on Lobbying in Second Quarter 2011
     PHARMA lobbied on implementation of aspects of the 2010 healthcare overhaul, including prices and rebates for drugs purchased through the Medicare program, strengthening Medicare anti-fraud measures, and eliminating an independent payment advisory board meant to hold down Medicare spending. The amount is an increase over the $4.65 million it spent a year earlier and the $4.54 million it spent in this year's first quarter.
     PHARMA's efforts are on legislation that would bar the marketing of authorized generic drugs, which allow makers of brand-name drugs to partner with a generic company to retain more revenue after their patents expire. Also the target of their lobbying activities are reforms concerning patent lawsuits and on other patent rules, and for the protection of intellectual property in foreign countries.
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Last Tax Holiday Shows U.S. Firms Cut Thousands of Jobs
     As many of the large corporations push for a tax holiday on more than one trillion dollars of overseas profits, a new survey has revealed that the last time such a measure was tried it ended in the loss of hundreds of thousands of jobs.
     The group has employed over 160 lobbyists to push its agenda, claiming that the companies will use the tax break to bring back money overseas and invest it in building new facilities and creating jobs.
     However, a report that studied the last time such a move was carried out, which was in 2004, allowed 843 firms to cut their tax rate on repatriating overseas profits from 35% to 5%. These firms brought home $312 billion dollars and avoided paying $92 billion dollars in government taxes in return for a promise to create jobs. The measure was called the American Job Creation Act.
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BMJ 2011 Sep 8; 343:d5364.
Time Trends for Mortality Among Patients with Early- vs. Late-Onset
Type 1 Diabetes

Early-onset patients are faring better, but late-onset patients are doing worse.
     In this population-based, nationwide cohort study of Finnish patients with type 1 diabetes, investigators examined time trends for mortality among 10,500 patients who developed early-onset disease (age range, 0–14 years) and 6800 who developed late-onset disease (age range, 15–29) between 1970 and 1999. Mean follow-up was 21.4 years.
     Excess mortality was higher in the early-onset group than in the late-onset group (standardized mortality ratio [SMR], 3.6 for early-onset and 2.8 for late-onset vs. the general population). At 20 years' duration of diabetes, SMRs for the early-onset group were lower in patients whose diagnoses were made in 1985–1989 than in patients with diagnoses in 1970–1974, whereas SMRs in the late-onset group were higher in patients whose diagnoses occurred at later dates. Mortality caused by chronic complications of diabetes decreased over time in the early-onset group but not in the late-onset group. Mortality caused by acute complications of diabetes and alcohol- and drug-related causes increased over time in the late-onset group.
     Comment: Mortality among patients with early-onset type 1 diabetes decreased over time, primarily because chronic complications of the disease became less prevalent. In contrast, mortality among patients with late-onset diabetes has increased over time, primarily because acute complications of the disease, which could be alcohol- or drug-related for many patients, have become more prevalent. Whether similar results are found in other populations remains to be seen.
Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine October 6, 2011
     Citation(s):Harjutsalo V et al. Time trends in mortality in patients with type 1 diabetes: Nationwide population based cohort study. BMJ 2011 Sep 8; 343:d5364.
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Arch Intern Med 2011 Sep 26; 171:1571
Depression Is Less Common in Women Who Drink Coffee
Four or more cups daily seemed to protect against developing depression.
     One prospective study involving men showed a reduced risk for depression with increased coffee consumption (Public Health Nutr 2010; 13:1215), and several studies have shown an association between increased coffee consumption and decreased risk for suicide. Using data from the Nurses' Health Study, investigators studied about 50,000 women who were free of depression at baseline; coffee consumption and new diagnoses of depression were documented during 10 years of follow-up.
     In analyses adjusted for numerous clinical and demographic variables, risk for depression in women who drank four or more cups of coffee daily was 20% lower than in women who drank one cup or less weekly. No association was observed between risk for depression and consumption of either decaffeinated coffee or caffeine from other sources (e.g., tea, chocolate); however, noncoffee sources probably contributed too little caffeine for meaningful assessment.
     Comment: These results are biologically plausible, because caffeine affects dopaminergic transmission as an adenosine-receptor antagonist. The finding that decaffeinated coffee doesn't lower risk for depression suggests that caffeine is the active component. However, confirmatory data from randomized trials would be preferable before we use these findings to make clinical recommendations.
Thomas L. Schwenk, MD Published in Journal Watch General Medicine October 6, 2011
     Citation(s):Lucas M et al. Coffee, caffeine, and risk of depression among women. Arch Intern Med 2011 Sep 26; 171:1571. (http://dx.doi.org/10.1001/archinternmed.2011.393)
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Relation Between Barrett's Esophagus and Adenocarcinoma Questioned
     The risk that Barrett's esophagus will lead to esophageal adenocarcinoma is about one quarter of previous estimates, according to a New England Journal of Medicine study. The finding calls into question current surveillance approaches for patients with the condition.
     Using the Danish national pathology registry, researchers identified some 11,000 patients who had Barrett's esophagus with or without dysplasia. They then looked for the later appearance of those patients in the Danish cancer registry.
     After a median follow-up of 5 years, the incidence rate for esophageal adenocarcinoma in patients with Barrett's esophagus was 1.2 cases per 1000 person-years (previous estimates hovered around 5.5). The relative risk for adenocarcinoma after a finding of Barrett's was some 11 times the risk in the general population — again, a several-fold decrease from previous estimates. Low-grade dysplasia at initial biopsy was associated with higher risk.
     The authors conclude that the risk "is so minor that in the absence of dysplasia, routine surveillance ... is of doubtful value."
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Research finds that spices may reduce insulin, triglyceride response
     New research published in the Journal of Nutrition have indicated that the addition of spices to a meal can help reduce insulin and triglyceride response. The small study consisted of six overweight yet healthy men, age range from 30 to 65 years. Led by Sheila West of Pennsylvania State University, the research found that when they added two tablespoons of culinary spices (combination of oregano, rosemary, black pepper, turmeric, garlic powder, cloves and paprika), compared with eating a meal without the spice additive, the subjects experienced an insulin response reduction of 21% and a 31% reduction in triglyceride response. West was quoted to say "Normally, when you eat a high-fat meal, you end up with high levels of triglycerides, a type of fat, in your blood. If this happens too frequently, or if triglyceride levels are raised too much, your risk of heart disease is increased. We found that adding spices to a high-fat meal reduced triglyceride response by abou t 30%, compared to a similar meal with no spices added."
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Studies have found cherries to be an inexpensive natural pain remedy
     An article in NaturalNews is bringing to light the benefits of cherries. There have been multiple studies done on the effect of pain reduction using cherries. Research published at the 2004 John Hopkins University, rats were injected with either a solution containing tart cherries or a prescription non-steroidal anti-inflammatory drug (NSAID) with exposure to either a heated surface or an inflammatory agent. The tart cherries significantly reduced pain sensitivity and at the highest dosage were as effective as the drug. The authors of the study concluded that tart cherries may have a beneficial role in reducing inflammatory pain. In a 2001 study at Michigan State University, the focus on the anthocyanins in cherries was found to be equivalent to two common over-the-counter painkillers (also NSAIDs) for inhibiting the COX-1 and COX-2 enzymes associated with inflammation. Every year, Oregon has the Hood to Coast 197 mile relay race, involving 1,000 relay teams. In 2009, scientists from Oregon's Health and Science University did a study on the impact of tart cherry juice on pain that athletes experienced while participating in the race. Participants drank 10.5 ounces of tart cherry juice twice daily for a week prior to the actual race and then every 8 hours during the race. At the end of the race itself, the cherry drinkers had less pain and faster muscle recovery. NSAIDs are often associated with side effects that are not experienced with cherries.
     In 2003, researchers at USDA's Agricultural Research Service were investigating the painful problem of gout. Gout is a type of arthritis caused by uric acid build up in the joints, specifically the toes. Their study involved ten healthy female volunteers that experienced gout. The test subjects ate 45 Bing cherries for breakfast every day. The researchers evaluated the urate levels, with are a precursor to uric acid, in blood plasma and in the urine. Within 5 hours of eating the cherries, urate decreased in blood plasma levels and increased in the urine. Two other areas of research involved evaluating C-reactive protein and nitric oxide, two inflammation markers. These also decreased after ingestion of cherries. The Oregon Health and Science Center conducted a recent study on women with fibromyalgia. 14 women were evaluated for muscle pain and weakness after exercising. Of the participan ts, half were given cherry juice and half a placebo for a ten day period. The results indicated that the subset given the cherry juice had a significant reduction in overall pain. Research overall suggests that cherries can be effective for different pain conditions. Both tart and sweet cherries contain anthocyanins, tart cherries have a higher content as well as a lower glycemic index. Tart cherries are also one of the few food sources that contain melatonin, which can be helpful for those that experience interruption of sleep due to pain.
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Pediatrics 2011 Oct; 128:e821
Food for Thought: The Effects of Race, Ancestry, and Environment on
Food Allergies

Black children were more likely than other children to have multiple food allergies, and African ancestry was associated with peanut sensitization.
     To explore associations between genetic ancestry and food allergen sensitization, researchers in Boston studied an urban birth cohort of 1104 children (mean age, 2.7 years) who were enrolled in the Children's Health Study. Parents self-categorized their infants as black (61%), Hispanic (22%), white (6%), or other (11%); 49% of households reported annual income of <US$30,000.
     Food sensitization was defined as detectable levels of specific IgE antibodies against any of eight common food allergens (egg white, cow's milk, peanut, soy, shrimp, walnut, wheat, and cod). Global genetic ancestry (African, European, and Asian) was determined by genotyping. Of interest, with each quartile of increasing African ancestry, a corresponding increase in peanut sensitization was noted. No association was found between self-reported black race and measures of peanut sensitization; however, black children were more likely to exhibit sensitization to three or more foods.
     Comment: The pathophysiology of food allergies is complicated and multifactorial. The authors admit that their findings might be attributable to environmental factors (e.g., early-life dietary patterns influenced by culture). I'm intrigued by a growing body of literature showing that environmental factors play a key role in food allergy: In a 2008 paper (J Allergy Clin Immunol 2008; 122:984), researchers reported that the prevalence of peanut allergy among Jewish schoolchildren in the U.K. was 10 times higher than among an age-matched cohort in Israel. This could not be accounted for by differences in genetic background. However, by 9 months of age, 69% of Israeli infants were eating peanuts, compared with only 10% of U.K. infants. Stay tuned: Our recommendation for dietary avoidance of certain foods — such as peanuts — during pregnancy, breast-feeding, and early infancy might need rethinking.
Louis M. Bell, MD Published in Journal Watch Pediatrics and Adolescent Medicine
October 12, 2011
     Citation(s):  Kumar R et al. Race, ancestry, and development of food-allergen sensitization in early childhood. Pediatrics 2011 Oct; 128:e821.
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Vitamin E Associated with Increased Prostate Cancer Risk
     Vitamin E supplements may significantly increase the risk for prostate cancer, according to a JAMA follow-up to a 2008 study.
     To test the efficacy of dietary supplements in preventing prostate cancer, researchers originally randomized over 35,000 relatively healthy men to one of four daily regimens: vitamin E (400 IU), selenium, both, or placebo. When no apparent benefit for prostate cancer risk was found, the data monitoring committee recommended stopping the study supplements. The researchers continued following the participants, however, and after roughly 7 years' total follow-up, men randomized to vitamin E alone showed a 17% relative increase in cancer risk over those on placebo (absolute risk with vitamin E vs. placebo: 10.9 vs. 9.3 cancers per 1000 person-years).
     The authors find no apparent biological explanation for the increased risk, and express concern about the widespread use of high-dose vitamin E in the U.S.
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Folic Acid Use Early in Pregnancy Might Protect Against Language Delay
in Offspring

     Children whose mothers took folic acid supplements early in pregnancy are at reduced risk for severe language delay, according to a JAMA study.
     Researchers in Norway (where foods are not fortified with folic acid) enrolled women around their 17th week of pregnancy and had them complete questionnaires about their use of supplements during the 4 weeks before and 8 weeks after conception. In addition, the women answered questions about their children's language development at 3 years of age.
     Of nearly 39,000 children included, 0.5% had severe language delay (defined as only 1-word or unintelligible utterances). After adjustment for confounders such as maternal education, children whose mothers had used folic acid supplements were 45% less likely to have severe language delay, compared with those whose mothers had not used any supplements.
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J Clin Oncol 2011 Oct 1; 29:3730.
Another Helping of Flaxseed for Breast Cancer?
High levels of serum enterolactone were associated with lower risk for death during follow-up in women with hormone receptor–negative tumors.
     The idea of using lifestyle changes to manipulate tumor behavior (and, by extension, breast cancer prognosis) is empowering in that it allows patients to play an active role in their own care. However, many strategies involving dietary alterations have yielded conflicting results, leaving patients and clinicians with less than robust data upon which to make decisions. Lignans — plant-derived substances found in flaxseed, sesame seeds, whole grains, vegetables, and fruits — are among the major sources of phytoestrogens in Western diets, and reportedly have anticancer properties. Lignans are metabolized by gut microflora into enterolactone (the principal metabolite). Epidemiologic studies have suggested that diets rich in lignans can lower incidence of postmenopausal breast cancer; however, dietary surveys have limitations, and two such studies came to opposing conclusions.
     To circumvent the shortcomings of dietary recall studies, German investigators assessed serum enterolactone levels in relation to clinical and pathologic prognostic factors and survival in 1140 postmenopausal women with breast cancer (age range, 50–74; stage I–IV and in situ cancers). At a median 6.1 years after diagnosis, women with hormone receptor–negative tumors who were in the highest quartile of serum enterolactone levels had significantly lower risk for death than did women in the lowest quartile (hazard ratio, 0.27). This effect was not seen in women with hormone receptor–positive tumors.
     Comment: The methodology for assessing enterolactone levels was rigorously vetted to ensure consistent results, but these results represent just one point in time; thus, whether raising enterolactone levels will improve clinical outcomes in the long term remains to be seen. Previous studies of β-carotene supplementation in patients with lung cancer showed that this dietary manipulation failed to improve outcomes, and might have worsened them. As noted by an editorialist, many factors can influence the bioavailability of lignans in individual patients; these include gut flora composition, alcohol intake, smoking, and the influence of other hormones on lignan metabolism. At present, the data still are insufficient to recommend a specific target intake of lignans.
William J. Gradishar, MD Published in Journal Watch Oncology and Hematology October 11, 2011
     Citation(s): Buck K et al. Serum enterolactone and prognosis of postmenopausal breast cancer. J Clin Oncol 2011 Oct 1; 29:3730.
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Women with Restless Legs Syndrome More Likely to Have Hypertension
     Women with frequent symptoms of restless legs syndrome (RLS) are significantly more likely to have hypertension than those without RLS, according to a cross-sectional study in Hypertension.
     More than 65,000 women (average age, 50) participating in the Nurses' Health Study II self-reported their RLS and hypertension status. Overall, 6% had RLS (defined as symptoms at least 5 times per month). The more often women experienced RLS symptoms, the more likely they were to have hypertension. In multivariable-adjusted analyses, women reporting RLS symptoms at least 15 times per month were 41% more likely to have hypertension than those with no RLS symptoms.
     Among the potential underlying mechanisms, the authors point out that most patients with RLS have periodic limb movements during sleep, which cause elevations in both heart rate and blood pressure at night and might lead to hypertension during the day.
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Coronary Disease Prevalence Declines in Most Areas of the U.S.
The age-adjusted prevalence of coronary heart disease in the U.S. has declined by roughly 10% in relative terms — from 6.7% in 2006 to 6.0% in 2010 — according to an MMWR report.
     Based on self-reports from national telephone interviews, the estimates show notably significant relative declines of over 20% in West Virginia and Missouri. Some states showed actual increases in prevalence (among them, Maine with 14% and New Mexico with 11%), but these did not achieve statistical significance.
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MM: At the risk of being a skeptic, it would seem that Chinese manufacturers have exhibited a lack of concern for the general welfare for those outside of China and when a study comes out that is diametrically opposed to information coming from the rest of the scientific community one must pause to ponder, “Is this true”. Only time and more study will tell.
Ann Intern Med 2011 Sep 20; 155:368.
No Association Found Between Urinary BPA and Type 2 Diabetes
New study calms some concerns about bisphenol A, widely used in plastic and metal containers for food and drink.
     Bisphenol A (BPA), a chemical component of hard plastic containers and linings of metal cans since the 1960s, has been detected in the urine of more than 90% of children and adults in CDC studies. In recent years, high urinary BPA concentrations have been associated with adverse health outcomes, including elevated risk for diabetes. In a cross-sectional study conducted in 2008 and 2009, Chinese researchers evaluated the relation between urinary BPA levels and impaired glucose tolerance and type 2 diabetes among nearly 3500 people in China. Glucose tolerance was assessed by measuring fasting glucose concentrations and performing oral glucose tolerance tests.
     After adjustment for multiple risk factors (e.g., age, family history of diabetes, waist circumference), no significant association was observed between urinary BPA level and the presence of impaired fasting glucose or diabetes.
     Comment: Much attention has been focused on the potential health risks of BPA. Earlier studies have shown a potential link between urinary BPA levels and disruption of pancreatic β-cell function, thyroid hormone alterations, and promotion of obesity. However, in this cross-sectional study, no association was found between BPA and diabetes.
Jamaluddin Moloo, MD, MPH Published in Journal Watch General Medicine October 13, 2011
     Citation(s): Ning G et al. Relationship of urinary bisphenol A concentration to risk for prevalent type 2 diabetes in Chinese adults: A cross-sectional analysis. Ann Intern Med 2011 Sep 20; 155:368. (http://www.annals.org/content/155/6/368.full)
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Diabetes Care 2011 Sep; 34:2054
α-Lipoic Acid Is Ineffective for Diabetic Neuropathy
Objective improvement was borderline, and symptom relief was nil.
     In small short-term trials, the antioxidant α-lipoic acid (ALA) — which is available without a prescription — provided some symptom relief in patients with diabetic neuropathy. Now, researchers have performed a long-term international industry-supported trial that involved 460 diabetic patients with mild-to-moderate distal sensorimotor neuropathy who were randomized to either daily ALA (600 mg) or placebo for 4 years.
     The primary endpoint was a standardized composite neuropathy score that reflected findings of both clinical neurological examination and nerve conduction studies of the lower extremities. Mean scores improved slightly in the ALA group and declined slightly in the placebo group, but the difference was not significant (P=0.1). Several secondary endpoints for changes in the neurological examination favored ALA (with P values in the 0.03 to 0.05 range). However, nerve conduction results and total symptom scores (for pain, burning, paresthesias, and numbness) were similar in the ALA and placebo groups at 2 and 4 years.
     Comment: In a previous 5-week study that focused on short-term symptom relief in patients with diabetic neuropathy, α-lipoic acid was significantly better than placebo (JW Gen Med Dec 12 2006). In this new 4-year trial, results were borderline for objective measurements, and ALA provided no symptom relief compared with placebo. These results do not support long-term use of ALA for patients with diabetic neuropathy.
Allan S. Brett, MD Published in Journal Watch General Medicine October 13, 2011
     Citation(s): Ziegler D et al. Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: The NATHAN 1 Trial. Diabetes Care 2011 Sep; 34:2054. (http://dx.doi.org/10.2337/dc11-0503)
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Lancet Oncol 2011 Oct; 12:1023
Intrauterine Devices Might Prevent More Than Pregnancy
Meta-analysis shows that IUDs provide protection against cervical cancer.
     Because intrauterine devices (IUDs) pass through the cervix, concern has been raised that use of these highly effective reversible contraceptives might affect risk for cervical cancer. To explore the possible associations between IUD use, cervical cancer risk, and presence of cervical human papillomavirus (HPV) DNA, researchers pooled international data from 10 case-control studies of cervical cancer and 16 survey studies of HPV prevalence. Information on IUD use was obtained via interviews, and HPV status was determined with polymerase chain reaction–based assays. The case-control studies involved 2205 women with cervical cancer and 2214 matched controls without cervical cancer; an additional 15,272 healthy women participated in the HPV prevalence studies.
     In meta-analyses adjusted for factors such as number of previous Pap smears, cervical HPV DNA status, and age at sexual debut, a protective association was found between ever use of an IUD and cervical cancer (odds ratio, 0.55; P<0.0001), whether squamous-cell carcinoma (OR, 0.56; P<0.0001) or combined adenocarcinoma and adenosquamous carcinoma (OR, 0.46; P=0.035). This benefit was not related to duration of IUD use. Among women without cervical cancer, IUD use was not associated with detection of cervical HPV DNA.
     Comment: The mechanisms by which intrauterine device use might lower the rate at which human papillomavirus infection progresses to cervical cancer remain unclear. The authors hypothesize that IUDs might exert this protective effect by inducing a chronic, low-grade, sterile inflammatory response in the endocervical canal that could modify the course of HPV infection. Alternatively, preinvasive cervical lesions might be removed when the device is placed or removed. Although the authors controlled for many confounders, the possibility remains that screening bias led to residual confounding. Although types of IUDs were not specified in this analysis, in the countries where these studies were conducted, few women use hormone-releasing IUDs; thus, future work should be aimed at examining whether levonorgestrel-releasing IUDs prevent cervical cancer.
Eleanor Bimla Schwarz, MD, MS Published in Journal Watch Women's Health October 13, 2011
     Citation(s): Castellsagué X et al. Intrauterine device use, cervical infection with human papillomavirus, and risk of cervical cancer: A pooled analysis of 26 epidemiological studies. Lancet Oncol 2011 Oct; 12:1023. (http://dx.doi.org/10.1016/S1470-2045(11)70223-6)
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MM: We have seen positive results with the use of intravaginal estriol, estradiol and testosterone for urinary incontinence, vaginal dryness, hot flashes, night sweats and libido. Acciording to the literature, this is a very safe delivery system and should be considered for women experiencing these symptoms. Call Mark Drugs for more information.
Menopause 2011 Sep; 18:962
Estradiol Vaginal Ring vs. Oral Oxybutynin for Overactive Bladder
Both treatments were equally effective at diminishing urinary frequency.
     Overactive bladder (urinary urgency and frequency with or without urge incontinence) affects as many as 40% of postmenopausal women. Behavior modification, pelvic floor exercises, and anticholinergic agents (e.g., oxybutynin chloride) are among first-line therapies; however, because side effects are common with such agents, topical estrogens are sometimes prescribed instead. In a manufacturer-funded, 12-week, randomized study, 59 postmenopausal women with urgency and frequency received either the ultralow-dose estradiol vaginal ring (Estring; 7.5 µg 17β-estradiol released daily) or oral oxybutynin (5 mg twice daily).
     Women in both groups had similar decreases in number of voids during a 24-hour period (from a mean of 14.9 to 10.4 for the vaginal ring [P<0.001] and from a mean of 14.7 to 11.7 for oxybutynin [P=0.003]) and similar significant improvements in quality of life. Therapy was discontinued by four vaginal ring recipients because of difficulty retaining the rings, and by four oxybutynin recipients because of adverse effects. At trial's end, 85% of ring users and 59% of oxybutynin users reported wanting to continue their assigned therapies (P=0.035).
     Comment: This study documents the effectiveness of the ultralow-dose estradiol vaginal ring for treating women with overactive bladder. Because the ring lacks the side effects of anticholinergic agents — and is inserted just once every 12 weeks — this treatment could appeal to many women. As noted by an editorialist, the vaginal ring is more expensive than either oxybutynin or estradiol vaginal cream, but some women might consider the higher cost to be worth it.
Robert W. Rebar, MD Published in Journal Watch Women's Health October 13, 2011
     Citation(s):Nelken RS et al. Randomized trial of estradiol vaginal ring versus oral oxybutynin for the treatment of overactive bladder. Menopause 2011 Sep; 18:962.
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Obstet Gynecol 2011 Sep; 118:576
Key Obstetric Risk Factors for Cerebral Palsy
Upper respiratory and gastrointestinal infections were not among the maternal infections associated with CP.
     In an analysis of epidemiologic risk factors for cerebral palsy (CP), Australian researchers used nationwide information from perinatal databases, CP registries, and maternal questionnaires to estimate the relative influences of various risk factors in a cohort of 587 children and adolescents (age range, 5–18) with CP and in 1154 controls.
     Certain maternal infections (particularly those that occurred during gestational weeks 21–40 and that caused fever) were associated with CP (41.4% of cases vs. 31.3% of controls; odds ratio, 1.6; P<0.001). However, common upper respiratory tract and gastrointestinal infections were not associated with CP. Other significant risk factors included birthweight <3rd percentile (OR, 11.8), gestational age <32 weeks (OR, 59.2), and twin birth (OR, 6.6). Factors not associated with CP included forceps- or vacuum-assisted birth, maternal age, diabetes, body-mass index outside the normal range, hypertension, alcohol consumption, anemia, and hypothyroidism.
     Comment: Because all study participants were white and of Australian descent, the ability to generalize these findings to other populations is limited. Nonetheless, because the authors used maternal questionnaires to supplement national data, the results provide additional details about certain cerebral palsy risk factors (possible recall bias notwithstanding). These findings confirm the four primary risk factors for CP (preterm birth, intrauterine growth restriction, perinatal infection, and multiple birth) while reassuring women who contract common upper respiratory and gastrointestinal infections during pregnancy that such infections do not raise risk for CP in their offspring.
Diane J. Angelini, EdD, CNM, FACNM, FAAN, NEA-BC Published in Journal Watch Women's Health September 29, 2011
     Citation(s): O'Callaghan ME et al. Epidemiologic associations with cerebral palsy. Obstet Gynecol 2011 Sep; 118:576.
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October 13, 2011
Vitamin D Fights TB
Findings reveal how vitamin D helps to fight tuberculosis, via a newly discovered immune response; study authors call for clinical trials
by Craig Weatherby
     You may have heard that vitamin D plays an essential role in the body's fight against infections. That proposition enjoys plenty of evidence, and just gained more support from a landmark tuberculosis study by researchers from the University of California, Los Angeles (UCLA) and Germany’s University of Cologne. As the authors concluded, “The present findings underscore the importance of adequate amounts of vitamin D in all human populations for sustaining immunity against infection.” (Fabri M et al. 2011) Vitamin D is proven essential for bone development … with lab, clinical and epidemiological evidence suggesting that it may help ameliorate or deter cancer and autoimmune diseases.
     We’ve reported on some of this research … see the “Vitamin D & Immunity” section of our news archive. Last year, the results of several studies greatly advanced the understanding of vitamin D’s role in the immune response to infections:

     The innate immune system is a relatively blunt weapon that babies use to fight infections while their adaptive immune system gradually develops defenses against specific bugs. Though the innate system appears less “sophisticated”, we still need it throughout life because the adaptive immune system can’t and doesn’t do it all.Now, the UCLA-German team reports that vitamin D plays an essential role in activating a full immune response to the bacteria behind tuberculosis (TB). This could be a hugely significant finding, since tuberculosis kills almost two million people yearly … and it’s been on the rise.
UCLA-German study finds that D fights TB
     Confirming the Danish and OSU findings from 2010, the new study shows that vitamin D – when present in adequate levels – fights TB by helping the innate and adaptive immune systems work together to fight the infection. It also fits with the well known fact that people with darker skin suffer increased susceptibility to tuberculosis, and areas of Africa have the highest TB rates … a vulnerability partly linked to higher levels of the skin pigment melanin. Melanin is more abundant in darker skin, which more effectively blocks absorption of the UV sunrays that burn skin but also trigger vitamin D production in the skin. 
What the study found
     The team found that T cells – which play a key role in immunity – release a protein called interferon-G that directs infected immune cells to attack the invading tuberculosis bacteria. However, this activation requires sufficient levels of vitamin D in order for the body to fight the tuberculosis bacteria effectively. Researchers next tested blood samples from healthy people who had higher or lower levels of vitamin D ... and the immune response was not triggered in the blood with lower vitamin D levels. But when adequate vitamin D was added to this deficient blood, the immune response got activated quite effectively. Scientists found that there was an 85 percent drop in colony-forming tuberculosis bacteria in human macrophage (immune system) cells that were effectively treated with interferon-G in the presence of sufficient vitamin D. 
Findings explain historical links between D and infections
     Dr. Mario Fabri from the University of Cologne put the team’s findings into context:
“Over the centuries, vitamin D has intrinsically been used to treat tuberculosis. Sanatoriums dedicated to tuberculosis patients were traditionally placed in sunny locations that seemed to help patients — but no one knew why this worked.” (UCLA 2011) As he said, “Our findings suggest that increasing vitamin D levels through supplementation may improve the immune response to infections such as tuberculosis.” (UCLA 2011) The team noted that vitamin D may help both innate and adaptive immunity, two systems that work synergistically to fight infections. Previous research by the UCLA-German team found that vitamin D played a key role in the production of a molecule called cathelicidin, which helps the innate immune system kill the tuberculosis bacteria. The current research demonstrates that vitamin D is also critical for the action of T cells, key players in adaptive immunity, a highly specialized system that humans acquire over time as they encounter different pathogens. “The findings of our previous research with innate immunity provided us with a new opportunity to take a look at the effects and role of vitamin D with acquired immunity, both critical systems of human defense,” said senior investigator Dr. Robert Modlin, from UCLA’s School of Medicine (UCLA 2011).
Both immune systems need vitamin D to fight TB
     Surprisingly, researchers found that although both the innate and acquired immune systems start out by using different receptors to trigger a complex chain reaction in infected cells to kill the tuberculosis bacteria, both converge early on to follow the same pathway that utilizes vitamin D.  Specifically, the researchers discovered that T cells released interferon-G, which not only activated the infected cells called macrophages to generate cathelicidin and other proteins to kill tuberculosis but, like a honing device, also ensured that these proteins were delivered to the compartment of the cell where the bacteria resides. The cells then gobbled up the infectious areas containing bacteria. “These current findings provide the first credible mechanistic explanation for how vitamin D critically contributes to acquired T cell immunity that protects us from infections, particularly tuberculosis,” said Dr. Modlin (UCLA 2011). Dr. Fabri noted that most people who test positive for tuberculosis display no symptoms, perhaps because they have enough vitamin D to keep the infection from developing into active disease. “At a time when drug-resistant forms of tuberculosis are emerging, understanding how to enhance natural innate and acquired immunity through vitamin D may be very helpful,” said co-author Barry Bloom, from the Harvard University School of Public Health (UCLA 2011). The UCLA-German researchers say the next step is to conduct clinical trials, to see whether vitamin D supplements can enhance the body’s resistance to tuberculosis and other infections. 
     Sources: Adams JS, Ren S, Liu PT, Chun RF, Lagishetty V, Gombart AF, Borregaard N, Modlin RL, Hewison M. Vitamin D-directed rheostatic regulation of monocyte antibacterial responses. J Immunol. 2009 Apr 1;182(7):4289-95. Copenhagen University (CU). Vitamin D crucial to activating immune defenses. March 3, 2010. Accessed at http://news.ku.dk/all_news/2010/2010.3/d_vitamin/. Fabri M et al. Vitamin D Is Required for IFN-γ–Mediated Antimicrobial Activity of Human Macrophages. Sci Transl Med 12 October 2011 3:104ra102. Gombart AF, Bhan I, Borregaard N, Tamez H, Camargo CA Jr, Koeffler HP, Thadhani R. Low plasma level of cathelicidin antimicrobial peptide (hCAP18) predicts increased infectious disease mortality in patients undergoing hemodialysis. Clin Infect Dis. 2009 Feb 15;48(4):418-24. Gombart AF, Saito T, Koeffler HP. Exaptation of an ancient Alu short interspersed element provides a highly conserved vitamin D-mediated innate immune response in humans and primates. BMC Genomics. 2009 Jul 16;10:321. Gombart AF. The vitamin D-antimicrobial peptide pathway and its role in protection against infection. Future Microbiol. 2009 Nov;4:1151-65. Review. Marina Rode von Essen, Martin Kongsbak, Peter Schjerling, Klaus Olgaard, Niels Ødum & Carsten Geisler. Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Published online: March 7, 2010 / doi:10.1038/ni.1851 Oregon State University (OSU). Key feature of immune system survived in humans, other primates for 60 million years. August 18, 2009. Accessed at http://www.eurekalert.org/pub_releases/2009-08/osu-kfo081809.php University of California, Los Angeles (UCLA). Scientists find vitamin D is crucial in human immune response to tuberculosis. Octo12, 2011ber
JAMA 2011 Sep 21; 306:1205

JAMA 2011 Sep 21; 306:1205
Erectile Function After Prostate Cancer Therapy
Two years after treatment, functional erections were reported by 48% of men with function before treatment.
     Men with newly diagnosed, low-risk prostate cancer face complicated decisions regarding treatment. Curative-intent therapy options include radical prostatectomy, external beam radiotherapy (EBRT), and brachytherapy, all of which provide high rates of disease control but can cause health-related quality-of-life (HRQOL) complications such as erectile dysfunction. However, a means to help patients predict risk for this impairment is lacking.
     To develop such a tool, investigators conducted a prospective, longitudinal, multicenter study of 1027 men with previously untreated clinical stage T1–T2 prostate cancer who had elected prostatectomy, EBRT, or brachytherapy as primary treatment from 2003 to 2006. Baseline characteristics, treatment details, and patient-reported outcomes were assessed before treatment and at 2, 6, 12, and 24 months after therapy. A multivariable model was internally validated using bootstrap resampling and externally validated using prostate cancer registry.
     In the cohort used for predictive-model development, which excluded men with unknown erection quality, results were as follows:

     Comment: As an editorialist notes, this was an observational study, which limits its utility. However, these results provide patients and physicians with better outcome data on posttreatment erectile dysfunction than has been previously available.
Robert Dreicer, MD, MS, FACP Published in Journal Watch Oncology and Hematology October 11, 2011
     Citation(s): Alemozaffar M et al. Prediction of erectile function following treatment for prostate cancer. JAMA 2011 Sep 21; 306:1205.
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Proc Natl Acad Sci U S A 2011 Sep 27; 108:16416.
Why Was the 1918 Influenza Pandemic So Lethal?
In a case series of influenza-related deaths during and just before the pandemic, all 68 cases had histopathological evidence of severe bacterial pneumonia.
     The worldwide influenza epidemic in 1918–1919 caused about 50 million deaths. In an effort to understand why the mortality rate was so high, investigators reexamined preserved lung tissue, stained slides, and records from 68 soldiers stationed at U.S. Army training camps who had died from probable influenza between May and October 1918.
     The men had a median age of 27 (range, 18–32), and nine of them had died during the 4 months before the pandemic was identified. Pneumonia or bronchopneumonia with or without influenza had been diagnosed in all 59 men for whom medical records were available.
     The 68 cases showed a spectrum of histopathological changes, including features of bronchitis (4/4 with available bronchial tissue), bronchiolitis (39/68), primary influenza viral pneumonia with diffuse alveolar damage (36/68), acute edema (41/68), acute hemorrhage (27/68). In addition, all 68 cases had evidence of severe acute bacterial pneumonia, and bacteria — predominantly gram-positive organisms morphologically consistent with Streptococcus pneumoniae, Streptococcus pyogenes, or Staphylococcus aureus — were found in recut tissue specimens from 63 of 67 cases. These results were concordant with bacterial lung-culture results recorded in 1918 for 44 of the cases. Influenza viral antigens were identified in alveolar lining cells, apical cells of bronchial epithelium, and hyaline membrane material, with no difference between prepandemic and pandemic cases. Analysis of influenza viral RNA from a subset of cases showed a shift from mixed "avian-like" and "human-like" glycan binding specificity in prepandemic cases to "human-like" specificity in pandemic cases.
     Comment: These data provide several key insights. First, the pandemic virus was circulating in the U.S. for at least 4 months before the pandemic was recognized. Second, the overall characteristics of influenza infection in the cases studied here were quite similar to those seen in fatal 2009 H1N1 influenza cases and were not suggestive of more-severe viral disease. Finally, mortality was universally associated with concurrent severe bacterial pneumonia, which today should be preventable with immunization or treatable with readily available antibiotics.
Richard T. Ellison III, MD Published in Journal Watch Infectious Diseases October 5, 2011
     Citation(s):Sheng Z-M et al. Autopsy series of 68 cases dying before and during the 1918 influenza pandemic peak. Proc Natl Acad Sci U S A 2011 Sep 27; 108:16416.
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October 3, 2011
Omega-3s Deemed Helpful in ADHD
Yale team finds that omega-3s add significant support for healthy attention and behavior  
by Craig Weatherby
     Parents of children – mostly boys – with attention-deficit/hyperactivity disorder (ADHD) may fear for their child’s educational and social progress, and happiness. ADHD may be triggered by diet in some kids, while a diagnosis of mild ADHD may represent the “medicalization” of one among many patterns of child development. Both questions remain unanswered, and the subject of debate.
     Recently, researchers from Yale University’s Child Study Center reviewed the existing clinical evidence and reported an encouraging finding: “Omega-3 fatty acid supplementation demonstrated a small but significant effect in improving ADHD symptoms.” (Bloch MH, Qawasmi A 2011). Before we look at their review in more depth (see “Yale team sees promising signs”, below), let’s review the ADHD landscape, and the history of omega-3s and childhood attention/behavior disorders to date.
Does diet cause ADHD? Can natural remedies replace drugs?
     Food additives and diets high in refined carbohydrates and sugar have been blamed for some ADHD cases. To date, the evidence supporting that hypothesis seems compelling but remains inconclusive: see “Food Additives Trigger ADHD in Clinical Trial” and “Attention Deficit Risks Raised by American Diet”. If a child is diagnosed correctly, given the right prescription, and monitored carefully, ADHD drugs can work well, with minimal or no adverse side effects. Still, it’s easy to understand why many parents remain reluctant to give children with relatively mild ADHD symptoms powerful brain-modifying drugs … whose modes of action are not fully understood. Parents should pay attention to the clinical evidence on drug alternatives, and well-documented links between diet and brain chemistry. It makes to search and scrutinize evidence for (and against) safe, biologically plausible nutritional supports for healthy development and behavior. They will find sometimes extravagant claims for alternative therapies, in the absence of good evidence for significant efficacy. So, doctors and parents alike should note the conclusion of an evidence review from Yale University … namely, that omega-3s from fish significantly promote improved attention and behavior.
Omega-3s and ADHD: Some background
     Kids with ADHD typically have lower omega-3 blood levels than their non-ADHD peers, and higher levels of omega-6 and saturated fats (Antalis CJ et al. 2006). And we’ve reported on several clinical trials that suggest omega-3s from fish may help ease ADHD symptoms in mild-to-moderate cases. Considered alone, none of the existing trials has possessed the statistical power needed to gain FDA approval for ADHD-related treatment claims for omega-3s. But evidence for the hypothesis that omega-3s can ameliorate ADHD continues to grow and enjoys plausible biological explanations. The evidence in favor of omega-3 fish fats cannot be responsibly ignored by people responsible for kids’ developmental health … especially boys, who constitute most ADHD cases.
For some background, see “Boys' Brains Sparked (and Calmed) by Omega-3 DHA”, “Kids' Attention Deficits Curbed by Omega-3s”, and “Fish Oil and ADHD: The New York Times Runs a Balanced Report”, which contains links to other reports on research in this realm. To bring the evidentiary picture up to date, researchers from Yale University performed a “meta-analysis” of the available clinical evidence, to gauge its quality and implications (Bloch MH, Qawasmi A 2011). 
Yale team sees promising signs in the existing evidence
     The Yale scientists’ meta-analysis included 10 randomized placebo-controlled clinical trials in which researchers tested omega-3 fish oil supplements among children diagnosed with ADHD. In all 10 trials – involving a total of 699 children – the efficacy of omega-3 fish oil supplements was measured by comparing children’s scores on standard tests of ADHD severity, before and after. The various trials used different fish oils containing varying amount of total omega-3s and varying proportions of the two key omega-3s – EPA and DHA – which share extensive evidence of exerting positive brain-health effects. As the researchers wrote, “Omega-3 fatty acid supplementation, particularly with higher doses of eicosapentaenoic acid [EPA], was modestly effective in the treatment of ADHD … compared with currently available pharmacotherapies [drug treatments] …” (Bloch MH, Qawasmi A 2011). In other words, they found that all fish oil improved ADHD symptoms, while fish oils providing the highest levels of EPA performed best. They went on to make an important point about omega-3s’ balance of clear safety and significant, albeit lesser efficacy:
“… given its relatively benign side-effect profile and evidence of modest efficacy, it may be reasonable to use omega-3 fatty supplementation to augment traditional pharmacologic [drug] interventions or for families who decline other psychopharmacologic options.” (Bloch MH, Qawasmi A 2011)
     Sources: Antalis CJ, Stevens LJ, Campbell M, Pazdro R, Ericson K, Burgess JR. Omega-3 fatty acid status in attention-deficit/hyperactivity disorder. Prostaglandins Leukot Essent Fatty Acids. 2006 Oct-Nov;75(4-5):299-308. Epub 2006 Sep 8. Bloch MH, Qawasmi  A. Omega-3 Fatty Acid Supplementation for the Treatment of Children With Attention-Deficit/Hyperactivity Disorder Symptomatology: Systematic Review and Meta-Analysis. J Am Acad Child Adolesc Psychiatry. Volume 50, Issue 10, Pages 991-1000, October 2011. Published online August 16, 2011. Accessed online at http://www.jaacap.com/article/S0890-8567(11)00484-9/abstract. Germano M, Meleleo D, Montorfano G, Adorni L, Negroni M, Berra B, Rizzo AM. Plasma, red blood cells phospholipids and clinical evaluation after long chain omega-3 supplementation in children with attention deficit hyperactivity disorder (ADHD). Nutr Neurosci. 2007 Feb-Apr;10(1-2):1-9. McNamara RK, Carlson SE. Role of omega-3 fatty acids in brain development and function: potential implications for the pathogenesis and prevention of psychopathology. Prostaglandins Leukot Essent Fatty Acids. 2006 Oct-Nov;75(4-5):329-49. Epub 2006 Sep 1. Review. Raz R, Gabis L. Essential fatty acids and attention-deficit-hyperactivity disorder: a systematic review. Dev Med Child Neurol. 2009;51:580–592 Richardson AJ. Omega-3 fatty acids in ADHD and related neurodevelopmental disorders. Int Rev Psychiatry. 2006 Apr;18(2):155-72. Review
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Article from Vital Choices Newsletter
October 3, 2011
Cancer Patients Lacked Vitamin D
Deficiency found common in cancer patients; Lowest levels linked to advanced tumors
by Craig Weatherby
     We’ve reported on some of the many epidemiological studies that link low vitamin D levels to increased cancer risks. While the sheer bulk of this non-clinical evidence suggests – very strongly – that vitamin D protects against common cancers, it cannot prove this hypothesis. For some background, peruse related articles in the “Vitamin D & Immunity” section of our news archive. A new study revealed that more than three in four of the participating cancer patients had “insufficient” levels of vitamin D. And it found the lowest levels among those in the most advanced stages of various cancers. It was not possible to tell whether the patients’ notably low vitamin D levels helped to cause their cancer or resulted from having cancer.
     The findings came from a study presented at the 53rd Annual Meeting of the American Society for Radiation Oncology.
     Lead author Thomas Churilla affirmed that many studies suggest a link between vitamin D and cancer risk or prognosis:
     “… there are various levels of evidence to support that vitamin D has a role in either the prevention or the prediction of outcome of cancer.” (ASTRO 2011)
 Cancer patients lacked vitamin D; Lowest levels linked to advanced tumors
     The study involved 80 men and 80 women (160 total; median age 64) at Northeast Radiation Oncology Center in Dunmore, Pennsylvania. Churilla’s team sought to determine whether the participants’ vitamin D levels could be linked to any types or aspects of cancer.  The five most common diagnoses were breast, prostate, lung, thyroid, and colorectal cancer. The analysis found low vitamin D levels in more than three in four (77 percent) of the patients, who had either deficient (less than 20 ng/mL) or sub-optimal (20-30 ng/mL) levels. Regardless of the age or sex of the patient, the lowest levels of vitamin D were seen in the patients experiencing the more advanced stages of their particular cancer.
Patients who were found to be vitamin D deficient were given vitamin D supplements, which increased their blood D levels by an average of 14.9 ng/mL. Churilla underlined the importance of pursuing the possibility that vitamin D deficiency may either promote cancer or worsen patient outcomes:
“Until recently, studies have not investigated whether vitamin D has an impact on the prognosis or course of cancer.” (ASTRO 2011)
 Accordingly, his team will follow the patients to see whether vitamin D supplementation has any impact on aspects of treatment or on survival.
 Cell study found vitamin D killed breast cancer
Last year, a team led by JoEllen Welsh of the State University of New York at Albany, treated human breast cancer cells with a potent form of vitamin D. Within a few days, half the cancer cells shriveled up and died. Welsh said the vitamin had the same effect as a drug used for breast cancer treatment. As she told ABC television’s Good Morning America, “What happens is that vitamin D enters the cells and triggers the cell death process. It's similar to what we see when we treat cells with Tamoxifen.” (Clarke S 2010) When her team tested vitamin D on breast cancer cells injected into mice, the tumors shrank by an average of more than 50 percent, and some vanished. (Similar results have been obtained in colon and prostate cancer tumors in mice.) Of course, studies on isolated human cancer cells and studies in animals often do not translate to positive clinical results in people. However, vitamin D’s role in the body’s immune response to infections was only discovered relatively recently. 
Clearly, much remains to be learned about the hormone-like “sunshine-and-seafood” nutrient’s role in fighting cancer.
Sources: American Society for Radiation Oncology  (ATRO). Vitamin D deficiency common in cancer patients; Predicts advanced disease. Presented on October 2, 2011, at the 53rd Annual Meeting of the American Society for Radiation Oncology (ASTRO). Accessed at http://www.astro.org/pressroom/presskit/AnnualMeeting/documents/ChurillaPR.pdf. Bischoff-Ferrari HA. Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes. Adv Exp Med Biol. 2008;624:55-71. Review. Clarke S. Vitamin D Shrinks Breast Cancer Cells. ABC News. Feb. 22, 2010. Accessed at http://abcnews.go.com/GMA/OnCall/study-vitamin-d-kills-cancer-cells/story?id=9904415. Costa JL, Eijk PP, van de Wiel MA, ten Berge D, Schmitt F, Narvaez CJ, Welsh J, Ylstra B. Anti-proliferative action of vitamin D in MCF7 is still active after siRNA-VDR knock-down. BMC Genomics. 2009 Oct 28;10:499. Grant WB, Holick MF. Benefits and requirements of vitamin D for optimal health: a review. Altern Med Rev. 2005 Jun;10(2):94-111. Review. Matthews D, LaPorta E, Zinser GM, Narvaez CJ, Welsh J. Genomic vitamin D signaling in breast cancer: Insights from animal models and human cells. J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):362-7. Epub 2010 Apr 20. Review. Vieth R. What is the optimal vitamin D status for health? Prog Biophys Mol Biol. 2006 Sep;92(1):26-32. Review.
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Obstet Gynecol 2011 Sep; 118:529
Breast Cancer in Women Younger Than 25
Although cancer is uncommon in this age group, all breast masses should be evaluated.
     Little published research addresses breast cancer in very young women. In a retrospective case series, investigators assessed diagnostic approaches, incidence, and outcomes in girls and women younger than 25 who received primary breast cancer diagnoses at Mayo Clinic between 1935 and 2005.
     Breast cancer was diagnosed in 12 women (age range, 18–24). Of 11 women with available clinical presentations and histories, 8 had self-detected breast masses, 1 noted bloody nipple discharge associated with constitutional symptoms, 1 had symptoms associated with disseminated malignancy, and 1 had an asymptomatic breast mass detected by a physician. Mean time between presentation and biopsy was 1.1 months (range, 0–16 months). Two women had strong family histories of breast cancer, six had weak family histories, and none were tested for BRCA mutations. Regional and local recurrences occurred in three women, and contralateral breast cancer occurred in two women (ovarian cancer was subsequently diagnosed in one). At the time of last follow-up (median, 25.5 months), four women had died from their breast malignancies, two were alive with disease, and five were alive with no evidence of disease.
     Comment: Because primary breast cancer in adolescents and young women is unusual (and benign breast conditions are relatively common), low suspicion of malignancy can delay diagnosis. In addition, breast malignancies in young women typically are more aggressive than those in older women. Thus, breast cancer survival is relatively poor in young women. The infrequency of malignancies in very young women should not prevent clinicians from evaluating breast masses in this age group. At minimum, assessment should include palpation and ultrasound imaging. Some clinicians believe that standard evaluation of breast masses in young women should include biopsy; however, the authors propose that tissue diagnosis should be reserved for women with clinical features that meet certain criteria. Lastly, the prevalence of suspected hereditary breast cancer in this case series (taken together with other reports that 10% of women with breast cancer who are younger than 40 harbor BRCA1 or BRCA2 mutations) underscores the appropriateness of offering genetic testing to young women with breast cancer.
Andrew M. Kaunitz, MD Published in Journal Watch Women's Health September 15, 2011
     Citation(s):Simmons PS et al. Breast carcinoma in young women. Obstet Gynecol 2011 Sep; 118:529 http://www.ncbi.nlm.nih.gov/pubmed/21860280?dopt=Abstract

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