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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
November 12, 2011

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Honey Isn't Honey Any More?
Public Health Group Wants Sodium Reduced
Lifestyle Drugs Increasing—But at What Price? Drug to Prevent Gray Hair Might
   Be Next in 'Lifestyle' Drug Pipeline
Dextrose Injections Have Osgood-Schlatter Disease on Its Knees
Ultraviolet Radiation Emitted by Tanning Beds Causes DNA Mutations
Mysterious Leg Lesions? Ask About Pedicures
Clinicians Don't Always Follow Guidelines for Osteoporosis
Compression Stockings for Obstructive Sleep Apnea?
Complications After Prostate Biopsies Are Rising
Chondroitin Sulfate Holds Promise for Hand Osteoarthritis
Serum Cholesterol Might Not Affect Mortality in Elders
Colonoscopy Protects Against Colorectal Cancer for as Long as 20 Years
Growing Hair with Botox
Intestinal Microflora Can Promote Viral Replication
B Vitamins or Meditation Ease Workers’ Stress
Mobile Phone Subscribers Don't Experience Higher Risks for Cancer –
   The Saga Continues…
Social Phobia Is Distinct from Shyness
Clopidogrel for Acute MI: 600 mg Beats 300 mg in a Randomized Trial
Transmission of Antibiotic-Resistance Genes by Bacteriophages
Omega-3s Boosted Fat, Sugar Metabolism in Mice

Honey Isn't Honey Any More?
     Most honey that is purchased in grocery stores today isn't "honey" according to the official definitions of honey. Honey must contain the bee pollen to be honey whereas today's honey is more purified. Most honey today is heated and forced at high pressure through very small filters to remove the pollen (which is the only foolproof method of identifying the actual source of the honey). Whereas most grocery stores sell the filtered honey, some of the natural stores and honey labeled "organic" honey usually still contains the pollen and is honey according to the official definition.
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Public Health Group Wants Sodium Reduced
     The American Public Health Association has passed a resolution calling for federal regulation of sodium in foods. Their goal is to reduce sodium in restaurant and processed foods by 75% in ten years through FDA regulation; this could be triggered by removing or changing the status of sodium from its current recognition of GRAS (generally recognized as safe).
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Lifestyle Drugs Increasing—But at What Price?
Drug to Prevent Gray Hair Might Be Next in 'Lifestyle' Drug Pipeline

     The lifestyle drug market is booming worldwide; it seems to pit problems of social or cosmetic nature against conditions threatening physical health or well-being. Some question whether or not vanity should assume equal importance pharmaceutically to authentic medical conditions.
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Pediatrics 2011 Nov; 128:e1121.
Dextrose Injections Have Osgood-Schlatter Disease on Its Knees
Three monthly injections of 12.5% dextrose/1% lidocaine significantly improved intractable knee pain in adolescent athletes.
     Osgood-Schlatter Disease (OSD) — a patellar tendon pathology with associated tibial tubercle apophysitis — is common in adolescents who compete in running and jumping sports. OSD can cause knee pain and affect activity for months to years and is treated primarily with rest. In a randomized double-blind study, researchers in Argentina compared treatment with 12.5% dextrose/1% lidocaine injections, 1% lidocaine injections, or usual care (exercises and 2 or more physical therapy appointments) in 54 athletes (age range, 10–17 years; 94% boys; 65 affected knees) with OSD. All participants had failed conservative treatment with 2 months of stretching/strengthening and played with pain for at least 3 months. In the dextrose/lidocaine and lidocaine-only groups, 0.5 mL of the solution was injected via a 27-gauge needle into the patellar tendon around its insertion on the tibia 3 to 6 times until pain during a single-leg squat disappeared. The assigned injection regimen was repeated in a blinded fashion each month for 3 months.
     After 3 months, pain severe enough to affect sports performance was significantly less common in the dextrose/lidocaine and lidocaine-only groups than in the usual-care group, (0%, 9%, and 41% of knees, respectively). Symptoms completely resolved significantly more often in the dextrose/lidocaine group than in the other two groups (66%, 23%, and 14%, respectively). Improvements persisted through 12 months of follow-up. Patients in the lidocaine-only and usual-care groups who did not improve after 3 months were offered open-label dextrose injections; by 6 months, improvement was equal to that in patients who received dextrose/lidocaine injections from the start. The injections were safe and well tolerated (10% of patients required acetaminophen for injection pain). Only patients in the usual-care group dropped out of their sport because of OSD.
     Comment: Dextrose injections have shown efficacy in other tendon and connective tissue conditions; they are thought to reduce neovascularity, pain-producing neuropeptides, or both. This study shows a promising option for adolescent athletes with stubborn OSD: either dextrose/lidocaine or lidocaine-only injections can help them play without performance-altering discomfort, and dextrose injections can help them play symptom free.
Cornelius W. Van Niel, MD Published in Journal Watch Pediatrics and Adolescent Medicine November 9, 2011
     Citation(s):Topol GA et al. Hyperosmolar dextrose injection for recalcitrant Osgood-Schlatter disease. Pediatrics 2011 Nov; 128:e1121.
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J Invest Dermatol 2011 Oct 6
Ultraviolet Radiation Emitted by Tanning Beds Causes DNA Mutations
UVA1 wavelengths, like UVB wavelengths, induce carcinogenic skin damage.
     In 2009, the World Health Organization declared tanning beds to be carcinogens (JW Dermatol Jul 30 2009), based largely on epidemiologic evidence. The tanning bed industry countered, using marketing practices remarkably like those employed by tobacco manufacturers (J Am Acad Dermatol 2010; 62:685). Solar-radiation–related mutation is primarily attributed to effects of ultraviolet B (UVB) radiation. The tanning industry claimed that the UVA1 wavelengths used in indoor tanning are safer. These investigators sought molecular evidence that the UVA1 radiation emitted by tanning beds also causes mutations in DNA.
     They exposed small areas of the skin of 12 healthy volunteers (Fitzpatrick sun-reactive skin types I and II) to UVA1 or UVB radiation at doses that produced comparable levels of erythema. In biopsy samples taken from the irradiated skin sites immediately after exposure, cyclobutane thymine dimers (which lead to UVB signature mutations in skin cancers) were present primarily in the basal layer of the epidermis in the UVA1-exposed sites, but primarily in the upper epidermis in UVB-irradiated sites. UVB produced more than 4 times as many cyclobutane thymine dimers as UVA1 and also produced 6-4 photoproducts, the other major type of DNA mutation observed after UV radiation. UVA1 irradiation did not produce 6-4 photoproducts. Both UVA1 and UVB activated repair mechanisms able to partially repair damaged DNA, with comparable repair rates.
     Comment: This evidence demonstrates that UVB and UVA1 have distinct effects on keratinocytes. Whereas the major site of UVB damage is the upper epidermis, most UVA1 damage showed up in the lower dermis — a particular concern because epidermal stem cells, which may be the targets cells of nonmelanoma skin cancers, are thought to reside in that location. These observations provide molecular evidence that the wavelengths of ultraviolet radiation emitted by tanning beds cause skin cancer, a finding we can use to counsel patients about the consequences of such devices. The findings also suggest that broad-spectrum sunscreens that protect against both UVA and UVB wavelengths will more effectively prevent skin cancer than those that block UVB alone.
Craig A. Elmets, MD Published in Journal Watch Dermatology November 4, 2011
     Citation(s):Tewari A et al. UVA1 induces cyclobutane pyrimidine dimers but not 6-4 photoproducts in human skin in vivo. J Invest Dermatol 2011 Oct 6; [e-pub ahead of print]. (http://dx.doi.org/10.1038/jid.2011.283).
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Clin Infect Dis 2011 Oct 15; 53:787
Mysterious Leg Lesions? Ask About Pedicures
Nail salon footbaths are implicated in furunculosis caused by atypical mycobacteria.
     Despite our near-constant exposure to rapidly growing nontuberculous mycobacteria (RGM), which are common colonizers of water supply systems, these organisms seldom make us sick. Or perhaps they do so more often than we recognize.
     Spurred by two local cases of RGM leg furunculosis apparently acquired in nail salons, North Carolina researchers combed public health records of two counties for additional cases during a 4-year period; they found 40 confirmed or probable cases in women and teenage girls, whose single or multiple leg lesions were caused most often by organisms in the Mycobacterium chelonae/abscessus group. The researchers visited some of the implicated nail salons, where they noted debris or visible biofilms in the footbaths more commonly than they did when they visited control salons without associated cases. However, footbath water samples yielded organisms in 15 of 24 salons, with no differences between case and control salons
     Comment: Women commonly shave their legs before pedicures; resulting nicks can provide a portal of entry for whatever organisms splash up from the footbath. Clinicians should keep this scenario in mind when patients with leg furunculosis fail to respond to standard empirical antistaphylococcal treatment.
Abigail Zuger, MD Published in Journal Watch General Medicine November 3, 2011
     Citation(s):Stout JE et al. Pedicure-associated rapidly growing mycobacterial infection: An endemic disease. Clin Infect Dis 2011 Oct 15; 53:787. (http://dx.doi.org/10.1093/cid/cir539)
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Menopause 2011 Oct; 18:1072
Clinicians Don't Always Follow Guidelines for Osteoporosis
Many women receive inappropriate screening and treatment.
     As the number of menopausal women continues to rise, osteoporosis screening and treatment assume greater importance. U.S. investigators conducted a study in women who had undergone dual x-ray absorptiometry from 2007 to 2009 to determine whether they met criteria for bone-mineral density (BMD) testing and subsequent treatment in accord with the 2006 North American Menopause Society (NAMS) guidelines. These guidelines specify that screening should not be initiated until age 65 (unless certain risk factors are present) and that treatment should be initiated only in osteoporotic women (or selected high-risk women with T scores between –2.5 and –2.0).
     Among 615 evaluable women (mean age, 62; 95% non-Latina white), 41% did not meet criteria for BMD assessment. In all, 22% of participants were using bisphosphonates, 11% were using hormone therapy, 3% were using raloxifene, and 1% were using calcitonin. Among 102 women with any indication for treatment, 35% were not using any of these pharmacologic therapies. Among 467 women who had no indications for treatment, 18% were receiving therapy with bisphosphonates, raloxifene, or calcitonin.
     Comment: These findings suggest that U.S. clinicians are inappropriately screening many women and are often failing to intervene appropriately when indications for treatment are present. The NAMS guidelines were updated in 2010 (JW Womens Health Feb 18 2010), and some clinicians might follow other guidelines; however, all current recommendations are similar. Educating patients about reasons that screening tests are not indicated can be challenging and time-consuming. Nonetheless, the heightened awareness of risks associated with long-term bisphosphonate use (JW Gen Med Dec 15 2009 and JW Gen Med Mar 3 2011) can facilitate conversations about why women at low risk generally do not need treatment.
Andrew M. Kaunitz, MD Published in Journal Watch Women's Health November 10, 2011
     Citation(s):Schnatz PF et al. Osteoporosis screening and treatment guidelines: Are they being followed? Menopause 2011 Oct; 18:1072
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MM: This may explain, at least in part why patients with sleep apnea who use the HCG weight loss protocol will typically see improvement in their sleep apnea while also seeing improvement in lower extremity edema and swelling.
Am J Respir Crit Care Med 2011 Nov 1; 184:1062
Compression Stockings for Obstructive Sleep Apnea?
This intervention seemed beneficial in patients with venous insufficiency.
     In recent years, studies have shown that overnight mobilization of fluid from the legs to the central circulation (also known as "nocturnal rostral fluid shift") can result in increased neck circumference and increased airway collapsibility. Could this phenomenon contribute to obstructive sleep apnea (OSA)? To find out, researchers in Paris conducted a randomized crossover trial involving 12 nonobese adults with known OSA and chronic venous insufficiency. Each person wore compression stockings during waking hours for 1 week and no compression stockings for 1 week. The hypothesis was that wearing compression stockings would prevent fluid accumulation in the legs during the day, resulting in less displacement of fluid into the neck while the patient was recumbent overnight.
     The mean number of apneas plus hypopneas during 1 week was significantly lower after the compression-stocking intervention than after the control period (31 vs. 48). As predicted, the mean overnight reduction in leg fluid volume and the mean overnight increase in neck circumference were significantly greater during the control period than during the compression-stocking period.
     Comment: In this small but provocative study, compression stockings reduced fluid accumulation in the legs during the day, resulting in less redistribution of fluid into the neck at night and improvement in OSA. If the findings can be corroborated, we might have a new adjunctive treatment for OSA — at least in patients with chronic venous insufficiency and perhaps in those with other causes of chronic leg edema.
Allan S. Brett, MD Published in Journal Watch General Medicine November 10, 2011
     Citation: Redolfi S et al. Attenuation of obstructive sleep apnea by compression stockings in subjects with venous insufficiency. Am J Respir Crit Care Med 2011 Nov 1; 184:1062. (http://dx.doi.org/10.1164/rccm.201102-0350OC)
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J Urol 2011 Nov; 186:1830
Complications After Prostate Biopsies Are Rising
A recent upsurge in infectious complications is worrisome.
     The rate of complications following prostate biopsy is relevant to the balance of benefits and harms from prostate cancer screening. Johns Hopkins urologists determined 30-day hospitalization rates after prostate biopsy in a random national sample of 17,000 Medicare participants who underwent biopsy procedures between 1991 and 2007.
     The 30-day hospitalization rate of 6.9% was significantly higher than the 2.9% rate among 135,000 randomly selected controls of similar age (for controls, a 30-day period was selected randomly). Exclusion of men with diagnosed prostate cancer — who might have been hospitalized for cancer treatment after positive biopsies — yielded a similarly elevated relative risk for hospitalization. Men in the biopsy group were at significantly higher risk than controls for hospitalizations with diagnostic codes for urinary or prostatic infection (0.4% vs. 0.2%) and for noninfectious complications such as hematuria or urinary retention (0.30% vs. 0.04%). The rate of hospitalizations for infectious complications rose significantly over time: It was consistently lower than 0.5% before the year 2000, but, more recently, it's been between 0.5% and 1.0%.
     Comment: The authors conclude that "there is a nontrivial risk of serious complications after prostate biopsy." These figures underestimate the total complication rates, given that some patients are treated in outpatient or emergency department settings. The authors also express concern that quinolone resistance might account for the temporal trend of increasing infection rates. Interestingly, a recent Canadian study also documented that the incidence of post-biopsy hospitalization for infection increased strikingly between 1996 and 2005 (J Urol 2010; 183:963).
Allan S. Brett, MD Published in Journal Watch General Medicine November 10, 2011
     Citation(s): Loeb S et al. Complications after prostate biopsy: Data from SEER-Medicare. J Urol 2011 Nov; 186:1830. (http://dx.doi.org/10.1016/j.juro.2011.06.057)
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Arthritis Rheum 2011 Nov; 63:3383
Chondroitin Sulfate Holds Promise for Hand Osteoarthritis
The drug conferred moderate symptom relief, compared with placebo.
     In randomized trials, chondroitin sulfate has not been much more effective than placebo for patients with hip or knee osteoarthritis (JW Gen Med Oct 7 2010). Now, Swiss researchers have examined whether chondroitin relieves pain in hand osteoarthritis; they randomized 162 patients with symptomatic and radiographically documented osteoarthritis of multiple hand joints to receive either chondroitin sulfate (800 mg daily) or placebo.
At 6 months, the mean reduction in pain on a 100-mm visual analog scale (mean baseline score, 54 mm) was 20 mm in the chondroitin group versus 11 mm in the placebo group — a significant difference. Improvement in a hand function score was also significantly greater with chondroitin than with placebo. Grip strength and use of rescue acetaminophen did not differ between groups.
     Comment: Chondroitin and its companion drug glucosamine have had a checkered history — with some successes and some failures — in randomized trials that involved patients with lower extremity osteoarthritis. According to the authors, this study is the first in which the effect of chondroitin on symptoms of hand osteoarthritis was examined. Clinicians can recommend the drug based on this trial, but corroborating studies would be ideal. The preparation used in this study consisted of chondroitins 4 and 6 sulfate of fish origin.
Allan S. Brett, MD Published in Journal Watch General Medicine November 8, 2011
     Citation(s):Gabay C et al. Symptomatic effects of chondroitin 4 and chondroitin 6 sulfate on hand osteoarthritis: A randomized, double-blind, placebo-controlled clinical trial at a single center. Arthritis Rheum 2011 Nov; 63:3383. (http://dx.doi.org/10.1002/art.30574)
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J Am Geriatr Soc 2011 Oct; 59:1779
Serum Cholesterol Might Not Affect Mortality in Elders
In healthy older persons, high cholesterol levels were associated with lower noncardiovascular-related mortality.
     Some studies suggest that high cholesterol levels in older people do not predict cardiovascular (CV) mortality (JW Gen Med Nov 15 1994) and, in fact, that they are associated with lower risk for non-CV death. Researchers in Rotterdam examined this issue in a population-based prospective study that involved 5750 older people (age range, 55–99; mean age, 69). At baseline, mean total and HDL cholesterol levels were 255 and 53 mg/dL, respectively.
     During median follow-up of 14 years, higher total cholesterol in those aged >65 was associated with lower non-CV–related mortality and lower cancer-related mortality in analyses adjusted for potential confounders. Moreover, no association was found between higher cholesterol and CV-related mortality in those aged 55 to 84; for those aged 85, the association again was inverse — higher cholesterol predicted lower CV-related mortality. When the researchers addressed "reverse causality" (the possibility that low baseline cholesterol was actually an effect of preterminal illness) by excluding participants who died during the first year of follow-up, results were similar.
     Comment: The possibility of a causal relation between very low cholesterol levels and higher noncardiovascular-related mortality in older people has been controversial for years; this study keeps the debate alive. The results also remind us that serum cholesterol as a predictor of CV-related death weakens as people age (although the complete lack of a positive association between total cholesterol and CV-related death in those aged 55–70 in this Dutch cohort is surprising). The clinical implication is that cholesterol-lowering drugs are unnecessary for elders at otherwise low coronary risk.
Allan S. Brett, MD Published in Journal Watch General Medicine November 8, 2011
     Citation(s): Newson RS et al. Association between serum cholesterol and noncardiovascular mortality in older age. J Am Geriatr Soc 2011 Oct; 59:1779.
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J Clin Oncol 2011 Oct 1; 29:3761
Colonoscopy Protects Against Colorectal Cancer for as Long as 20 Years
High-quality baseline colonoscopy, followed by colonoscopy at the recommended screening and surveillance intervals, is the most cost-effective strategy.
     A previous case-control study conducted in Germany showed that colonoscopy protects against colorectal cancer (CRC) for ≥10 years (JW Gastroenterol Oct 27 2006). Now, the same investigators have conducted a larger study involving 1692 patients with CRC and 1896 population controls recruited from 22 hospitals and population registers in Germany between 2003 and 2007. They used medical records and interviews to determine participants' history of colonoscopy.
     After a single negative colonoscopy, the age- and sex-adjusted odds ratios for CRC at the following intervals were 0.14 (1–2 years), 0.10 (3–4 years), 0.26 (5–9 years), 0.36 (10–19 years), and 0.41 (≥20 years). Risks were reduced similarly in men and women. Risks were also reduced in those with or without a family history of CRC in a first-degree relative, even though the risk reductions did not reach significance in the positive family history group after 4 years, possibly because of small numbers of patients. Risk reductions were seen for both right-sided and left-sided cancers, although the absolute reductions were greater for left-sided than right-sided cancers during the first 10 years after a negative colonoscopy. The only group without a substantial risk reduction over time was current smokers: Risk was clearly reduced for the first 4 years, but was less certain thereafter, with wide confidence intervals and few participants remaining in the study.
     Comment: A recent case-control study from this same research group in Germany (where colonoscopy is performed mainly by gastroenterologists) showed that colonoscopy within the preceding 10 years was associated with a 56% reduction in right-sided colon cancer and a >80% reduction in left-sided colon cancer (JW Gastroenterol Feb 4 2011). The current investigation shows that a negative colonoscopy is associated with substantial risk reductions in both right-sided and left-sided colon cancers. Recent studies in the U.S. have suggested that many average-risk Medicare patients undergo repeat colonoscopy at 5 years, even when the initial colonoscopy is negative (JW Gastroenterol Jun 10 2011). Although the present findings are unlikely to change recommendations in the U.S., they provide additional support for clinicians following the U.S. guidelines to perform colonoscopy at 10-year rather than 5-year intervals. The most cost-effective way to prevent CRC is with high-quality baseline colonoscopy, followed by colonoscopy at the recommended screening and surveillance intervals.
Douglas K. Rex, MD Published in Journal Watch Gastroenterology October 14, 2011
     Citation(s):Brenner H et al. Long-term risk of colorectal cancer after negative colonoscopy. J Clin Oncol 2011 Oct 1; 29:3761.
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Plast Reconstr Surg 2010 Nov; 126:246e
Growing Hair with Botox
Mean hair counts rose and mean hair loss slowed after injections of botulinum toxin A.
     Botulinum toxin A (BTX A) has been used for the treatment of wrinkles, hyperhidrosis, and headaches. Now, here comes an open-label pilot study from Canada of BTX A to treat androgenic alopecia. The study was supported by an educational grant from the manufacturer, and the authors hold intellectual property rights to the treatment process.
     Fifty males with Norwood/Hamilton alopecia classes II to IV had injections to the scalp muscles (divided equally to the frontalis, temporalis, periauricular, and occipitalis) of a total of 150 units of BTX A, followed by a second session 24 weeks later. Assessment included change in hair counts in a 2-cm scalp area, changes in hair loss counts collected by lint roller from the subject's pillow, and patient responses to a questionnaire. The 60-week study period consisted of a 12-week baseline lead-in period and two 24-week treatment periods following each BTX A treatment session.
     In the 40 patients who completed the study, mean hair counts increased 18% from baseline to 48 weeks after the initial injection, a statistically significant change. Hair loss was also significantly reduced, by a mean of 39%. The reduction in hair loss and increase in hair counts were not correlated. The treatment response rate was 75%. The subjects noted statistically significant increased hair growth. No adverse events were noted.
     Comment: The proposed mechanism for hair growth in androgenic alopecia after botulinum toxin A treatment is that paralysis of the scalp muscles enhances blood flow to the scalp by reducing the tension on the scalp skin. Because the conversion to dihydrotestosterone (DHT) is enhanced in a low-oxygen environment, oxygenated blood reduces this conversion and increases conversion to estradiol. This might be the same mechanism by which minoxidil affects androgenic alopecia. The 18% increase in hair count is similar to that achieved with finasteride. How injecting BTX A into scalp muscles could be protected as intellectual property is difficult to see.
George J. Hruza, MD Published in Journal Watch Dermatology November 10, 2011
     Citation(s):Freund BJ and Schwartz M. Treatment of male pattern baldness with botulinum toxin: A pilot study. Plast Reconstr Surg 2010 Nov; 126:246e.
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Science 2011 Oct 14; 334:249
Intestinal Microflora Can Promote Viral Replication
In mouse models, infection by certain retroviruses and enteric viruses is mediated by interaction with intestinal bacteria.
     Given that bacteria are universally present in the mammalian gastrointestinal tract, viruses that infect intestinal cells always do so in the presence of this microbiota. Two research teams have now determined that infection with certain viruses depends on the presence of these bacteria.
     In studies with a murine retrovirus (mouse mammary tumor virus [MMTV]), Kane and colleagues found that this pathogen could not readily infect either antibiotic-treated or germ-free mice. To elucidate this observation, they conducted a series of experiments involving multiple mouse strains and cell lines. They found that MMTV infection was dependent on the development of an immune-evasion pathway, which was driven by production of the immunoregulatory cytokine interleukin-10. Interleukin-10 production was induced by bacterial lipopolysaccharide that was bound to MMTV virions in the gut.
     Kuss and colleagues, using a mouse model of poliovirus infection, found that infection via the oral route was markedly suppressed by pretreatment of mice with antibiotics that eliminated gut flora, and that infection was enhanced by subsequent reintroduction of intestinal bacteria. In contrast, viral infection via intraperitoneal injection remained uninfluenced by the gut microflora. Antibiotics did not directly interfere with viral replication, and poliovirus infection was not influenced by antibiotics in mice that had had antibiotic-resistant intestinal microflora. Infection following oral inoculation with a mouse reovirus (an unrelated enteric virus) was similarly suppressed by pretreatment with antibiotics that eradicated gut flora. In in vitro studies, infectivity of poliovirus was enhanced by exposure to intestinal microflora or certain bacterial surface polysaccharides, including peptidoglycan and lipopolysaccharide.
    Comment: These observations suggest that several viruses use the intestinal microbiota to mediate host infection, contradicting the long-standing belief that antibiotic therapy has no effect on viral infection. A clinically relevant question arising from this work is whether antibiotic therapy might diminish the effectiveness of the oral polio vaccine. A whole new field of investigation has now emerged.
Richard T. Ellison III, MD Published in Journal Watch Infectious Diseases November 2, 2011
     Citation(s):Kuss SK et al. Intestinal microbiota promote enteric virus replication and systemic pathogenesis. Science 2011 Oct 14; 334:249.
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B Vitamins or Meditation Ease Workers’ Stress
Clinical trials show that either a high-dose B vitamin supplement or meditation can significantly reduce work-related stress
by Craig Weatherby
     The normal challenges of daily living keep us alert, and can actually improve mood and performance. However, excessive or chronic stress can lead to over-activity of the body's hormonal stress-response systems. When these systems are working normally, they normalize sleep, appetite, energy, and sex drive, and promote healthy mood.

Sustained stress elevates levels of cortisol, the so-called “death hormone”. This imbalance alters levels of neurotransmitters in the brain and literally shrinks the hippocampus region, which plays a key role in memory and emotion. Unhealthy personal and occupational stress is on the rise worldwide … as exemplified by an epidemic of suicides among bankrupt Indian farmers and over-worked Chinese tech factory employees. Less dramatically but equally important, direct connections have been found between excess stress and greater risk for heart disease and auto-immune disorders such as inflammatory bowel disease (Backé EM et al. 2011; Rampton DS 2011).

     Now, the results of a three-month trial from Australia’s Swinburne University of Technology suggest that increasing your B vitamin intakes could significantly reduce work-related stress. According to study leader Professor Con Stough, “Anything we can do to reduce work-related stress is a good thing,” he said. “By lowering stress, we also lower the risk of health problems such as cardiovascular disease, depression and anxiety. And from an organizational perspective, reducing your workers’ stress is likely to improve productivity.” (SUT 2011) Interestingly, Stough’s team published a separate trial this year, showing that a “mental silence” type of meditation – specifically, Sahaja Yoga meditation – also reduced workers’ stress and improved their mood (Manocha R et al. 2011).

Aussie study finds B vitamin complex effective
At the beginning of the three-month trial, the researchers assessed 60 participants on factors such as personality, work demands, mood, anxiety and strain, and then re-evaluated them at 30 and 90 days (Stough C et al. 2011). At the end of the trial, those in the vitamin B group reported much lower levels of work stress than they did at the beginning of the trial. In fact, the vitamin B group experienced an almost 20 percent drop in stress levels, while those in the placebo group showed no significant change. The results may have been muddied somewhat by the presence of two traditional relaxation herbs – oats (Avena sativa) and passion flower (Passiflora incarnata) – in the commercial supplement used in the trial.

Professor Con Stough said that this was the first study of its kind – an assertion borne out by our search of the medical literature. He opined that the results were not very surprising, given the important role that B vitamins play in cognitive function. As he said, “B vitamins, which are found in whole unprocessed foods such as meat, beans and whole grains, are integral to the synthesis of neurotransmitters critical to psychological wellbeing. But the reality is that many people don’t get enough B vitamins from their diet, so they are turning to vitamin supplementation.” (SUT 2011)

While the results of the study present a strong case for B vitamin supplementation, Professor Stough acknowledged the need for more research: “Ideally we’d like to conduct a larger trial with more participants that would investigate the effects of Vitamin B supplementation over two to three years.” (SUT 2011) The study was jointly funded by supplement maker Blackmores and Swinburne University of Technology’s Centre for Psychopharmacology.

The Blackmores supplement used in the trial (Executive B Stress Formula) contained these active ingredients:

Sources: Backé EM, Seidler A, Latza U, Rossnagel K, Schumann B. The role of psychosocial stress at work for the development of cardiovascular diseases: a systematic review. Int Arch Occup Environ Health. 2011 May 17. [Epub ahead of print] Manocha R, Black D, Sarris J, Stough C. A randomized, controlled trial of meditation for work stress, anxiety and depressed mood in full-time workers. Evid Based Complement Alternat Med. 2011;2011:960583. Epub 2011 Jun 7. Rampton DS. The influence of stress on the development and severity of immune-mediated diseases. J Rheumatol Suppl. 2011 Nov;88:43-7. Stough C, Scholey A, Lloyd J, Spong J, Myers S, Downey LA. The effect of 90 day administration of a high dose vitamin B-complex on work stress. Hum Psychopharmacol. 2011 Oct;26(7):470-6. doi: 10.1002/hup.1229. Epub 2011 Sep 8. Swinburne University of Technology (SUT). Vitamin B reduces work stress. November 9, 2011. Accessed at http://www.swinburne.edu.au/chancellery/mediacentre/media-centre/news/2011/11/vitamin-b-reduces-work-stress
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BMJ 2011 Oct 20; 343:d6387.
Mobile Phone Subscribers Don't Experience Higher Risks for Cancer – The Saga Continues…
A long-term follow-up report is reassuring.
     Whether mobile phone use is associated with cancer and central nervous system (CNS) tumors is unclear. In the only cohort study to date, mobile phone subscribers did not experience greater risk for any cancer or CNS tumors than nonsubscribers (J Natl Cancer Inst 2006; 98:1707). The same investigators now report long-term follow-up results.
     Mobile phone subscriber data were linked with the Danish National Cancer Register. Approximately 3.2 million Danes (age, ≥30) were categorized as subscribers (nearly 360,000 people) or nonsubscribers. Subscribers signed their first contracts between 1982 and 1995. During follow-up (1990–2007), more than 250,000 cancers and nearly 11,000 CNS tumors occurred. After adjustment for multiple factors, subscribers did not have elevated risk for all cancers, smoking-related cancers, or CNS tumors compared with nonsubscribers. Restricting analysis to people with the longest subscriptions (≥13 years), or analyzing data by CNS tumor type (e.g., glioma) and location (e.g., parietal lobe), did not affect the results.
     Comment: In this large nationwide cohort study, mobile phone subscribers did not experience higher risks for cancer or CNS tumors than nonsubscribers. A notable limitation of this study is that mobile phone subscription — rather than amount of time spent on the phone — was used as a measure of use. Nevertheless, these results should be reassuring for the billions of mobile phone users worldwide.
Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine November 10, 2011
     Citation(s):Frei P et al. Use of mobile phones and risk of brain tumours: Update of Danish cohort study. BMJ 2011 Oct 20; 343:d6387. (http://dx.doi.org/10.1136/bmj.d6387) http://www.ncbi.nlm.nih.gov/pubmed/22016439?dopt=Abstract
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Pediatrics 2011 Nov; 128:917
Social Phobia Is Distinct from Shyness
Teens who met criteria for social phobia reported greater impairment and were more likely to have psychiatric comorbidities than youth who rated themselves as shy.
     To determine if social phobia (a type of anxiety disorder) is a distinct entity or merely the "medicalization" of common human shyness, NIH investigators analyzed data from 10,123 adolescents (age range, 13–18 years) who participated in the nationally representative National Comorbidity Survey Replication Adolescent Supplement. Adolescents completed a structured diagnostic interview that assessed a broad range of mental health disorders. Those who met all eight lifetime DSM-IV criteria for social phobia, including one or more social fears, were classified as having social phobia, regardless of shyness. Adolescents were considered shy if they reported being "very" or "somewhat" shy around same-aged peers they did not know very well and did not meet social phobia criteria. Other assessments included impairments in the past year during chores, school/work, family relationships, and social life; prescribed psychiatric medication use; and lifetime treatment for anxiety disorders.
     Overall, 43% of males and 51% of females rated themselves as shy, but only 12% of these youth met criteria for social phobia. Five percent of youth who did not rate themselves as shy met social phobia criteria. The prevalence of social phobia increased with age (6.3% of 13- to 14-year-olds, 9.6% of 15- to 16-year-olds, and 10.4% of 17- to 18-year-olds). Compared with shy adolescents, those with social phobia were significantly more likely to have an anxiety disorder (odds ratio, 2.79), major depressive disorder (OR, 2.06), oppositional defiant disorder (OR, 1.99), or drug use disorder (OR, 3.27). They also had significantly greater impairment in school/work, family relationships, and social life. Only 23% of adolescents with social phobia sought professional treatment for anxiety, and just 12% received psychiatric medication.
     Comment: These results contradict the notion that social phobia is "medicalization" of a normal human emotion. The major distinction between social anxiety and shyness is that the anxiety associated with social phobia results in impairments that are significant enough to negatively impact one or more life areas (school, work, relations with friends or family). Few adolescents with social phobia ever sought treatment for anxiety or received psychiatric medication, which indicates that we need a better system for identifying these youth and helping them get the care they really need to treat the social phobia and other identified comorbidities. The SCARED screening tool is a standardized instrument to screen for child anxiety disorders in primary care and includes questions about shyness and specific anxieties.
Alain Joffe, MD, MPH, FAAP Published in Journal Watch Pediatrics and Adolescent Medicine November 9, 2011
     Citation(s):Burstein M et al. Shyness versus social phobia in US youth. Pediatrics 2011 Nov; 128:917.
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J Am Coll Cardiol 2011 Oct 4; 58:1592.
Clopidogrel for Acute MI: 600 mg Beats 300 mg in a Randomized Trial
In a randomized study underpowered for clinical endpoints, mean infarct size was significantly smaller with the higher loading dose.
     Guideline recommendations for a clopidogrel loading dose of 600 mg in patients with acute myocardial infarction (MI) are based on data from observational studies and extrapolated from randomized, controlled trial findings in patients undergoing nonurgent percutaneous coronary intervention (PCI). In this randomized, multicenter, European study, investigators compared a 600-mg loading dose of clopidogrel with a 300-mg dose in 201 patients undergoing primary PCI for ST-segment-elevation MI. Baseline patient and procedural characteristics were similar in the two dose groups.
     The primary endpoint — infarct size measured by biomarker levels — was significantly reduced with the higher clopidogrel dose: Median total creatine kinase-myocardial band mass over 72 hours was 2070 ng/mL in the high-dose group versus 3029 ng/mL in the low-dose group. Secondary endpoints favored the high-dose group as well, including a trend toward better Thrombolysis in MI flow grade and a slightly higher mean left ventricular ejection fraction at discharge (52.1% vs. 48.8%, P=0.026). The 30-day rate of adverse events (death, repeat MI, target-vessel revascularization, stroke) was also lower with the 600-mg dose than with the 300-mg dose (5.8% vs.15.0%, P=0.049). Rates of major and minor bleeding did not differ significantly between the two groups.
     Comment: The results of this small randomized study support the advantage of a 600-mg loading dose of clopidogrel before primary PCI and are consistent with the known action of the drug and with previously demonstrated benefits of antiplatelet therapy for acute MI. How this clopidogrel dose compares with other, more potent agents (prasugrel, ticagrelor) for this indication will require further study.
Howard C. Herrmann, MD Published in Journal Watch Cardiology November 9, 2011
     Citation(s):Patti G et al. Outcome comparison of 600- and 300-mg loading doses of clopidogrel in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: Results from the ARMYDA-6 MI (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Myocardial Infarction) randomized study. J Am Coll Cardiol 2011 Oct 4; 58:1592.
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Antimicrob Agents Chemother 2011 Oct; 55:4908.
Transmission of Antibiotic-Resistance Genes by Bacteriophages
Coliphage DNA isolated from cattle, pig, and poultry waste was found to harbor typical resistance genes in high concentrations.
     Bacteria can acquire antibiotic-resistance genes (ARGs) in several ways, including conjugative transfer of mobile elements, transformation by naked DNA, and transduction by bacteriophages. Recent studies have suggested that bacteriophages may be more important in this process than previously believed. To explore this issue, researchers examined the potential role of bacteriophages in spreading ARGs in animal environments.
     The study involved 71 fecal waste samples from various animals, collected in slaughterhouses and farms in Spain. Escherichia coli and other fecal coliform bacteria were determined to be present. Coliphage DNA was purified from the samples and tested for resistance genes by conventional and quantitative polymerase chain reaction. ARGs such as blaCTX-M, blaTEM, and mecA were detected in densities as high as 6 log10 gene copies per milliliter or gram of sample.
     Comment: The distribution of ARGs by bacteriophages has attracted little attention so far but likely is an important driving force in the spread of antibiotic resistance. Bacteriophages can transmit ARGs even in the absence of antibiotic pressure and are believed to serve as environmental vectors for them. As noted by the authors, phages persist better in aquatic environments (including human and animal wastewater) than their bacterial hosts or free DNA.
Thomas Glück, MD Published in Journal Watch Infectious Diseases November 9, 2011
     Citation(s): Colomer-Lluch M et al. Bacteriophages carrying antibiotic resistance genes in fecal waste from cattle, pigs, and poultry. Antimicrob Agents Chemother 2011 Oct; 55:4908.
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Omega-3s Boosted Fat, Sugar Metabolism in Mice
Fish fats improved metabolic functions common to mice and men and tied to diabetes and heart disease; human studies have been mixed but generally positive
by Craig Weatherby
     Most animal studies find that omega-3s reduce metabolic risk factors for diabetes and heart disease.  
The outcomes of human clinical trials are more mixed … especially with regard to insulin resistance ... a major metabolic risk factor for diabetes. That said, recent trials have yielded encouraging signs. To learn more, browse articles in the “Omega-3s & Metabolic Health” section of our news archive.

The short-chain “green” omega-3 in plant foods (ALA) generally exerts fewer, smaller effects in the body, compared with the long-chain “marine” omega-3s (EPA and DHA) found in fish fat and all human cells. However, some animal and human studies suggest that both types of omega-3s may help deter diabetes: see “Green & Marine Omega-3s May Deter Diabetes”. Now, the authors of a study in mice report that omega-3-rich diets may help to reduce the risk of diabetes and heart disease in these animals … and therefore, possibly in people.

Mouse study yields new evidence of omega-3s’ metabolic promise
The study was led by professor Bernhard Breier, Ph.D., of New Zealand’s Massey University, and included researchers from Germany and Australia (Nuernberg K et al. 2011). Dr. Breier noted that “omega-3s are especially beneficial for health in aging because they improve carbohydrate and fat metabolism”. (MU 2011) And he said that theirs is the first study to provide direct evidence of omega-3s’ ability to enhance the ways in which blood sugar and fat in our bodies are used. Overall, the results in these tiny rodents showed that a diet high in omega-3 fatty acids promoted the burning of stored body fat and sugar (glucose), and promoted a healthier fat-storage pattern. The benefits were smaller in chubby mice with genetic traits proven to predispose rodents and people to obesity and to metabolic disorders (diabetes and heart disease).

Omea-3 benefits prove strongest in leaner mice
The aim of the study was to test the effect of two high-fat diets on the fatty acid profiles in the animals’ tissues and organs, and on the “expression” of genes that control insulin levels. The scientists used two groups of mice:

The chubby mice displayed an “energy storage phenotype” characterized by high body weight, higher food intake, more body fat, higher liver weight, and higher blood levels of free fatty acids, leptin, and insulin. The term “phenotype” refers to an animal or person’s observable characteristics or traits, which result from genetic and environmental factors. Leptin is a hormone-like “signaling” protein that tells the brain the body has had enough to eat.

Obese people have high leptin (and body fat) levels, because they are resistant to its appetite-suppressing effects … just as people with type 2 diabetes have high insulin (and blood sugar) levels because they are resistant to insulin’s sugar-uptake effects.

In contrast, the lean, active mice displayed an “energy usage phenotype” characterized by lower body weight, less food intake, smaller body fat deposits, lower liver weight, and lower blood levels of free fatty acids, leptin, and insulin.

Outcomes show metabolic benefits from omega-3s
At 29 days of age, mice in both groups were divided into three groups and fed one of three diets for eight weeks:

The omega-3s fed to the mice were “long-chain” EPA and DHA from fish fat. After two months, the omega-3-rich diet lowered cholesterol levels and improved insulin action and fat metabolism in both groups of mice (chubby and lean).
However, the chubby, obesity-prone mice responded less well than the leaner variety, due no doubt to their genetic traits. The fatty acid composition of the animals’ muscle and liver tissues was affected differently by the two different high-fat diets:
Both high-fat diets caused leptin levels and body fat to rise in the chubby mice.

Professor Breier says this study has shown for the first time that the “insulin signaling cascade” becomes more active when diets are rich in omega-3 fatty acids. And as he noted, the results showed that “The omega-3 fatty acids in our diet can help how energy in our body is used.” (MU 2011) He went on to highlight the study’s implications for human health:
“These findings are important because the aging process is closely linked with a higher risk of developing metabolic syndrome – a clustering of risk factors for heart disease, diabetes and obesity.” (MU 2011) Fish fat can't prevent diabetes or cure it ... but much evidence indicates that the metabolic effects of omega-3s help delay or amelioerate diabetes and cardiovascular disease and blunt their mutually reinforcing effects.

So it seems important to get ample omega-3s ... especially to counteract the pro-inflammatory excess of omega-6 fats, which stems from Americans's huge intake of omega-6-rich vegetable oils and the many home, prepared, and packaged foods made with them.
Sources: Cottin SC, Sanders TA, Hall WL. The differential effects of EPA and DHA on cardiovascular risk factors. Proc Nutr Soc. 2011 May;70(2):215-31. Epub 2011 Feb 24. Review. Massey University. Omega-3 key in reducing diabetes and heart disease. Oct. 31, 2011. Accessed at:

Nuernberg K, Breier BH, Jayasinghe SN, Bergmann H, Thompson N, Nuernberg G, Dannenberger D, Schneider F, Renne U, Langhammer M, Huber K. Metabolic responses to high-fat diets rich in n-3 or n-6 long-chain polyunsaturated fatty acids in mice selected for either high body weight or leanness explain different health outcomes. Nutr Metab (Lond). 2011 Aug 11;8(1):56. doi:10.1186/1743-7075-8-56 Mustad VA, Demichele S, Huang YS, Mika A, Lubbers N, Berthiaume N, Polakowski J, Zinker B. Differential effects of n-3 polyunsaturated fatty acids on metabolic control and vascular reactivity in the type 2 diabetic ob/ob mouse. Metabolism. 2006 Oct;55(10):1365-74.

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