Exposure to infant siblings during early life and risk of multiple sclerosis

Context  The "hygiene hypothesis" has implicated sibship as a marker of infection load during early life and suggests that exposure or reexposure to infections can influence the developing immune system. Viral infection has also been implicated in the pathogenesis of multiple sclerosis (MS). Objectives  To evaluate whether exposure to infant siblings in early life is associated with the risk of MS, and to explore the possible mechanism for any apparent protective effect, including altered Epstein-Barr virus (EBV) infection patterns. Design, Setting, and Patients  Population-based case-control study in Tasmania, Australia, from 1999 to 2001 based on 136 cases of magnetic resonance imaging–confirmed MS and 272 community controls, matched on sex and year of birth. Main Outcome Measure  Risk of MS by duration of contact with younger siblings aged less than 2 years in the first 6 years of life. Results  Increasing duration of contact with a younger sibling aged less than 2 years in the first 6 years of life was associated with reduced MS risk (adjusted odds ratios [AORs]: <1 infant-year, 1.00 [reference]; 1 to <3 infant-years, 0.57 [95% confidence interval {CI}, 0.33-0.98]; 3 to <5 infant-years, 0.40 [95% CI, 0.19-0.92]; 5 infant-years, 0.12 [95% CI, 0.02-0.88]; test for trend, P = .002). A history of exposure to infant siblings was associated with a reduced IgG response to EBV among controls. Controls with at least 1 infant-year contact had a reduced risk of infectious mononucleosis and a reduced risk of very high composite EBV IgG titers (AOR, 0.33; 95% CI, 0.11-0.98) compared with other controls. The inverse association between higher infant contact and MS was independent of EBV IgG titer. Conclusion  Higher infant sibling exposure in the first 6 years of life was associated with a reduced risk of MS, possibly by altering childhood infection patterns and related immune responses.      

Retrospective reports of college students' childhood problems

College students and a subsample of their mothers and fathers participated in a study examining their retrospective reports of childhood emotional and behavioral problems experienced by college students. College students and their mothers and fathers exhibited moderate correspondence in their recollection of internalizing and externalizing problems that college students experienced during their childhood. In contrast, college students tended to endorse significantly greater levels of both internalizing and externalizing problems relative to their mothers and fathers. Current psychological symptoms predicted the greater endorsement of childhood internalizing and externalizing problems by college students and the greater endorsement of college students' childhood internalizing problems by their mothers. Further, college students' current perceptions of their parents predicted their endorsement of childhood internalizing problems, and college students' current masculinity and femininity predicted their endorsement of childhood externalizing problems. Results of this study emphasized the importance of noting factors that may be related to retrospective reports.     

Colonoscopic polypectomy

Despite the frequency with which polypectomy is performed, there is a paucity of information on what technical aspects of polypectomy most effectively remove polyps and minimize complications. The practice of polypectomy is based largely on the observational experience of experts and what gastroenterology fellows have learned from their attending physicians and from experts in postgraduate courses. Moreover, polypectomy technique is not consistent across the United States. In this technique update, the author presents his own methods for treating and observing small, large pedunculated, and large sessile polyps and discusses the advantages, disadvantages, and complications of each technique.     

Heparin-induced hyponatremia

OBJECTIVE: To report a case of hyponatremia in a patient receiving systemic unfractionated heparin (UFH) therapy and parenteral nutrition. CASE SUMMARY: A 70-year-old African American woman was started on parenteral nutrition for postoperative ileus following an elective surgical procedure. Three days later, she was diagnosed with a pulmonary embolism and intravenous UFH therapy was initiated. During the 7-day course of UFH therapy, the patient's serum sodium concentration steadily declined and urine sodium concentration progressively increased. Physical examination revealed no signs or symptoms of hypo- or hypervolemia. The patient's serum potassium concentration increased modestly, although significant hyperkalemia was not observed. After discontinuation of UFH, serum concentrations of both sodium and potassium returned to baseline levels. DISCUSSION: Although heparin-induced hyperkalemia is well documented, cases associated with substantial hyponatremia have been reported less frequently. An objective causality assessment revealed that the adverse drug reaction was probable in this case. Hyponatremia and hyperkalemia result from the antagonism of aldosterone by UFH within the zona glomerulosa of the adrenal glands. CONCLUSIONS: The use of UFH may result in significant hyponatremia as well as hyperkalemia. Reversal of these electrolyte disturbances occurs after discontinuation of heparin.     

Off-pump myocardial revascularization is associated with less incidence of stroke in elderly patients

Several recent studies have highlighted the potential benefits of using off-pump coronary artery bypass (OPCAB) surgery, particularly in high-risk patients. The aim of this meta-analysis is to assess the effect of OPCAB on the incidence of stroke compared with coronary artery bypass grafting using cardiopulmonary bypass (CPB) in elderly patients. We performed a meta-analysis of all observational studies, published in MEDLINE between 1999 and 2002 and a comparison between the OPCAB and CPB techniques in elderly patients was performed with the outcome of interest being the incidence of stroke. Elderly patients were defined as those aged 70 years or older. Nine studies are included in the meta-analysis. The total number of subjects included was 4,475 patients, of which, 1,253 underwent OPCAB (28%) and 3,222 (72%) underwent CPB. The meta-analysis showed that the OPCAB technique was associated with significantly lower incidence of stroke in elderly patients compared with the CPB technique (1% vs 3%), with an odds ratio of 0.38% to 95% (CI, 0.22 to 0.65). We did not identify any significant heterogeneity and funnel plot asymmetry between the studies included in the meta-analysis. Meta-regression analysis including variables predicting stroke, mortality, and study characteristics did not show any associations affecting the calculated odds ratio of stroke. Despite the fact that this is a meta-analysis of observational studies and adjustment for differences in baseline risk factors between OPCAB and CPB patients was not possible, we believe that this study suggests that the OPCAB technique might be associated with reduced incidence of stroke in the elderly patients undergoing coronary artery bypass grafting.     

Simvastatin modulates angiotensin II signaling pathway by preventing Rac1-mediated upregulation of p27

Recent experimental observations have suggested that statins may exert modulatory effects on a number of pathobiological processes beyond their cholesterol-lowering properties. Some of the pleiotropic effects of statins seem to be mediated by their ability to block the synthesis of isoprenoid intermediates, which serve as important lipid attachments required for the proper function and activation of the small GTP-binding proteins. The current study explored the modulatory effects of simvastatin (SMV) on the angiotensin II (Ang II)-induced Rac1-mediated, upregulation of cyclin-dependent kinase inhibitor p27. Ang II (100 nM) stimulation of rat mesangial cells induced a significant increase in p27 protein expression. Co-treatment of cells with SMV (1 microM) inhibited Ang II-induced upregulation of p27 protein. Addition of mevalonate (200 microM) or geranylgeranyl pyrophosphate (5 microM) reversed the inhibitory effect of SMV on p27 protein expression, suggesting that the effect of SMV is geranylgeranyl dependent. This study also provides evidence for a sequential link between Ang II stimulation and downstream activation of Rac1, intracellular H2O2 production, and Akt kinase leading to upregulation of p27 protein in mesangial cells. It was also shown that SMV, by inhibiting Rac1 activity, reversed Ang II-induced increase in intracellular H2O2 production, Akt activation, and p27 protein expression. The data presented in this study not only elucidate Ang II-mediated signaling cascade in mesangial cells but also demonstrate for the first time the modulatory effects of SMV on Ang II-induced signaling pathway at the cell cycle level.     

Computed tomographic colonography (virtual colonoscopy): a multicenter comparison with standard colonoscopy for detection of colorectal neoplasia

Context  Conventional colonoscopy is the best available method for detection of colorectal cancer; however, it is invasive and not without risk. Computed tomographic colonography (CTC), also known as virtual colonoscopy, has been reported to be reasonably accurate in the diagnosis of colorectal neoplasia in studies performed at expert centers. Objective  To assess the accuracy of CTC in a large number of participants across multiple centers. Design, Setting, and Participants  A nonrandomized, evaluator-blinded, noninferiority study design of 615 participants aged 50 years or older who were referred for routine, clinically indicated colonoscopy in 9 major hospital centers between April 17, 2000, and October 3, 2001. The CTC was performed by using multislice scanners immediately before standard colonoscopy; findings at colonoscopy were reported before and after segmental unblinding to the CTC results. Main Outcome Measures  The sensitivity and specificity of CTC and conventional colonoscopy in detecting participants with lesions sized at least 6 mm. Secondary outcomes included detection of all lesions, detection of advanced lesions, possible technical confounders, participant preferences, and evidence for increasing accuracy with experience. Results  A total of 827 lesions were detected in 308 of 600 participants who underwent both procedures; 104 participants had lesions sized at least 6 mm. The sensitivity of CTC for detecting participants with 1 or more lesions sized at least 6 mm was 39.0% (95% confidence interval [CI], 29.6%-48.4%) and for lesions sized at least 10 mm, it was 55.0% (95% CI, 39.9%-70.0%). These results were significantly lower than those for conventional colonoscopy, with sensitivities of 99.0% (95% CI, 97.1%->99.9%) and 100%, respectively. A total of 496 participants were without any lesion sized at least 6 mm. The specificity of CTC and conventional colonoscopy for detecting participants without any lesion sized at least 6 mm was 90.5% (95% CI, 87.9%-93.1%) and 100%, respectively, and without lesions sized at least 10 mm, 96.0% (95% CI, 94.3%-97.6%) and 100%, respectively. Computed tomographic colonography missed 2 of 8 cancers. The accuracy of CTC varied considerably between centers and did not improve as the study progressed. Participants expressed no clear preference for either technique. Conclusions  Computed tomographic colonography by these methods is not yet ready for widespread clinical application. Techniques and training need to be improved.      

Anxiolytic-like profile in Wistar, but not Sprague–Dawley rats in the social interaction test

Rationale The social interaction test is a valuable behavioural model for testing anxiolytic drugs in rodents, quantifying the level of social behaviour between pairs of rats.Objective The aim of the present study was to assess the appropriateness of the social interaction test for use with a Sprague–Dawley rat line, because of increasing use of this strain in targeted mutagenesis research.Methods Sprague–Dawley and Wistar rats received either diazepam or mCPP or were exposed to different environmental conditions (lighting, social isolation prior testing, habituation, testing-time). General anxiety-related parameters measured were: duration of active social contact, frequency of active social contact, latency to first contact. Different forms of active social contact were recorded: number of crawls, follows and sniffs. Secondly, aversion-induced hippocampal serotonin release and serotonin content in brain regions were measured.Results In Wistar rats habituation to the test substantially increased the time of social contact, an effect comparable with treatment with diazepam (1 mg/kg), whereas changes in the lighting level had less impact. Latency to the first contact increased under anxiety-reducing conditions, the frequency of contacts did not change consistently. Sprague–Dawley rats behaviour did not change under varying environmental conditions, and treatment with diazepam had only sedating effects at higher doses (5 mg/kg). Anxiogenic doses of mCPP caused reduced social interaction in both strains. Serotonin release and serotonin content were higher in the anxious Wistar rats.Conclusions Different rat strains as well as differing test conditions have a major impact on the outcome of this animal test for anxiety.     

Antidepressant-like effect of nicotinamide adenine dinucleotide in the forced swim test in rats

Nicotinamide adenine dinucleotide (NADH), a cosubstrate for energy transfer in the oxidative phosphorylation, has supposedly beneficial effects on central nervous system (CNS)-related diseases, e.g., shown in an open study with depressive patients. To our knowledge there are no data concerning the efficacy of NADH in animal tests. Acute effects of NADH and the precursor nicotinamide, compared to controls and the antidepressants desipramine and fluoxetine, were examined in the forced swim test (FST) in Wistar rats. NADH, but not nicotinamide, reduced immobility and increased swimming behaviour in the FST, with a minimum effective dose of 5 mg/kg. NADH-induced behavioural profile was similar to fluoxetine, but different from desipramine. Since NADH did not induce hyperlocomotion but even decreased motor activity in the open field test, the antidepressant-like effect cannot be attributed to an increase in motor activity. These data support an antidepressant potential of NADH.