The CCTTT pentanucleotide microsatellite in iNOS promoter influences the clinical outcome in <Emphasis Type="Italic">P. falciparum</Emphasis> infection

To assess the hypothesis that nitric oxide (NO) is critical in the pathogenesis of cerebral malaria, we analyzed those single nucleotide polymorphisms (SNPs) and microsatellite (MS) of the promoter region of inducible nitric oxide synthase (iNOS) gene which are known to enhance the NO production in vivo. A total of 428 (204 severe, 224 mild) adult patients living in the eastern part of India were analyzed. The single nucleotide substitutions −954G→C was found to be very rare, and −1173C→T was absent in this population. But interestingly, longer forms of MS were found to be significantly associated with severe malaria (OR = 2.89, 95% CI = 1.955–4.295, P < 0.0001), and the linear regression analysis revealed that the risk of severe malaria significantly increases as the summed repeat number in an individual increase (OR = 1.16, P = 0.0013). Further, the median plasma level of nitrate/nitrite (NOx) was observed to be high in mild patients compared to severe patients, and the level of parasitemia was significantly low among mild patients than severe ones. These findings suggest that the CCTTT repeats in iNOS may play a key role in the pathogenesis of severe malaria. Statement of authorship  G DhangdaMajhi: conducted laboratory analysis of samples and performed statistical analysis of the data, B N Mohaptra: selection and provision of treatment to the patients, S K Kar: clinicopathological analysis and interpretation of data, M R Ranjit: conception/design of the study, execution, and interpretation of the data and drafting the paper.     

An updated meta-analysis to assess the effectiveness of psychological interventions delivered by psychological specialists and generalist clinicians on glycaemic control and on psychological status

Objective

To update a meta-analysis and determine the effectiveness of psychological interventions on glycaemic control measured by HbA_1c and psychological status in type 2 diabetes and to compare effects when interventions are delivered by generalist clinicians compared to psychological specialists.

Methods

We used the original review protocol and searched the Cochrane central register of controlled trials, Medline, Embase, PsychLIT, and Google Scholar from February 2003 (end of previous review) to March 2007. We extracted data on the participants, interventions, delivery methods, comparison groups and outcome measures.

Results

35 trials were reviewed and meta-analysis of 19 trials (n = 1431), reporting HbA_1c found a reduction in HbA_1c by 0.54% (−0.32; 95% CI: −0.47 to −0.16). In nine trials (n = 832) interventions were delivered by diabetes or general clinicians reducing HbA_1c by 0.51% (−0.27; 95% CI: −0.50 to 0.04). In nine trials, interventions (n = 561) were delivered by psychological specialists reducing HbA_1c by 0.57% (−0.36; 95% CI: −0.61 to 0.12). Meta-analysis of 13 trials reporting psychological status found psychological status to be lower in the intervention groups −0.56 (95% CI: 1.00 to −0.13). Trial quality for the majority of studies remained poor.

Conclusion

Our findings suggest that psychological and general clinicians are similarly effective in delivering psychological interventions, however, effect sizes for all clinicians have reduced since the earlier review.

Practice implications

Psychological training opportunities for generalist clinicians could lead to wider availability of effective psychological care.     

The important role of radiation therapy in early-stage diffuse large B-cell lymphoma: time to review the evidence once again

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma in the USA, and approximately one-third of patients present with early stage, localized disease. While significant controversy still exists regarding the appropriate management of these patients, the overwhelming evidence from a wide range of studies over the last 40 years points to the superior efficacy of combined-modality therapy for this disease. The current standard of care for the vast majority of early-stage DLBCL cases now involves a combination of chemotherapy, immunotherapy and consolidation radiotherapy. Using this multimodality approach, very high rates of local control can be achieved, which will translate into significant survival benefits for patients with localized disease. The use of intensive immunochemotherapy without radiation therapy requires formal testing and validation in a randomized clinical trial before it can be used as an alternative treatment regimen for early-stage DLBCL. In this article, we discuss the results of the key randomized trials, critical retrospective studies and recent clinical trials, which collectively address the important role of radiotherapy in the treatment of early-stage DLBCL.     

Intermittent antegrade cardioplegia: isolated heart preservation with the Asporto heart preservation device

BACKGROUND: A major problem in procurement of donor hearts is the limited time a donor heart remains viable. After cardiectomy, ischemic hypoxia is the main cause of donor heart degradation. The global myocardial ischemia causes a cascade of oxygen radical formation that cumulates in an elevation in hydrogen ions (decrease in pH), irreversible cellular injury, and potential microvascular changes in perfusion. OBJECTIVE: To determine the changes of prolonged storage times on donor heart microvasculature and the effects of intermittent antegrade perfusion. MATERIALS AND METHODS: Using porcine hearts flushed with a Ribosol-based cardioplegic solution, we examined how storage time affects microvascular myocardial perfusion by using contrast-enhanced magnetic resonance imaging at a mean (SD) of 6.1 (0.6) hours (n = 13) or 15.6 (0.6) hours (n = 11) after cardiectomy. Finally, to determine if administration of cardioplegic solution affects pH and microvascular perfusion, isolated hearts (group 1, n = 9) given a single antegrade dose, were compared with hearts (group 2, n = 8) given intermittent antegrade cardioplegia (150 mL, every 30 min, 150 mL/min) by a heart preservation device. Khuri pH probes in left and right ventricular tissue continuously measured hydrogen ion levels, and perfusion intensity on magnetic resonance images was plotted against time. RESULTS: Myocardial perfusion measured via magnetic resonance imaging at 6.1 hours was significantly greater than at 15.6 hours (67% vs 30%, P = .00008). In group 1 hearts, the mean (SD) for pH at the end of 6 hours decreased to 6.2 (0.2). In group 2, hearts that received intermittent antegrade cardioplegia, pH at the end of 6 hours was higher at 6.7 (0.3) (P = .0005). Magnetic resonance imaging showed no significant differences between the 2 groups in contrast enhancement (group 1, 62%; group 2, 40%) or in the wet/dry weight ratio. CONCLUSION: Intermittent perfusion maintains a significantly higher myocardial pH than does a conventional single antegrade dose. This difference may translate into an improved quality of donor hearts procured for transplantation, allowing longer distance procurement, tissue matching, improved outcomes for transplant recipients, and ideally a decrease in transplant-related costs.     

The role of perceived norms in the stigmatization of mental illness

Background  Past research on stigmatization of the mentally ill has emphasized the importance of beliefs about mental illness in determining preferred social distance to those with such illnesses. In the current paper we examine the importance of perceived social norms in improving the prediction of social distance preferences. Methods  Two hundred university students completed scales measuring their beliefs about either depression or schizophrenia; their perception of relevant social norms and their preferred level of social distance to someone with schizophrenia or depression. Measures of social desirability bias were also completed. Results  The proportion of variance in preferred social distance was approximately doubled when perceived norms were added to beliefs about illness in a regression equation. Perceived norms were the most important predictor of social distance to an individual with either illness. A general preference for social distance towards a control, non-ill person was also an independent predictor of behavioral intentions toward someone with either schizophrenia or depression. Conclusions  Perceived social norms are an important contributor to an individual’s social distance to those with mental illness. Messages designed to influence perceived social norms may help reduce stigmatization of the mentally ill.     

Psychosocial factors and inflammation in the multi-ethnic study of atherosclerosis

BACKGROUND: Psychosocial factors are associated with the development and progress of cardiovascular disease, but the pathological mechanisms remain unclear. We examined the associations of psychosocial risk factors for cardiovascular disease with concentrations of inflammatory markers among healthy adults and assessed the extent to which these associations are mediated by behaviors, body mass index (BMI), and diabetes mellitus. METHODS: This cross-sectional study used data from the baseline examination of the Multi-Ethnic Study of Atherosclerosis, a multisite study of 6814 men and women aged 45 to 84 years. Regression analyses were used to estimate associations of cynical distrust, chronic stress, and depression with serum levels of C-reactive protein, IL-6, and fibrinogen before and after adjustment for socioeconomic position, behaviors, BMI, and diabetes. RESULTS: Higher levels of cynical distrust were associated with higher levels of inflammatory markers. The percentage differences (95% confidence intervals [CIs]) comparing the 80th and 20th percentiles of the scale were 7% (3%-11%) for IL-6; 9% (2%-16%) for C-reactive protein; and 1.3% (0.1%-2.4%) for fibrinogen. Higher levels of chronic stress were associated with higher concentrations of IL-6 and C-reactive protein. The percentage differences (95% CIs) comparing 2 and 0 ongoing stressful circumstances were 4% (1%-8%) for IL-6 and 5% (1%-11%) for C-reactive protein. Depression was positively associated with the level of IL-6 (percentage difference [95% CI] comparing the Center for Epidemiologic Studies-Depression Scale scores of >or=21 vs <21 was 7% [1%-14%]). Associations of psychosocial factors with inflammatory markers were reduced by 20% to 55% after adjustment for behavioral factors and by 45% to 100% after adjustment for BMI and diabetes, mostly owing to the effect of BMI. No associations remained after controlling for socioeconomic position, behaviors, BMI, and diabetes. CONCLUSIONS: Psychosocial factors are associated with higher levels of inflammatory markers, most consistently for cynical distrust. Results are compatible with a mediating role of BMI, behaviors, and diabetes.     

Long-term effects of a community intervention for early identification of first-episode psychosis

Objective: To assess whether an Early Case Identification Program (ECIP) for first‐episode psychosis (FEP), which showed no significant short‐term effects, has a delayed impact on duration of untreated psychosis (DUP). Method: Using a historical control design, FEP patients were assessed on clinical variables over three consecutive phases, 2 years prior, 2 years during and 3 years after implementation of the ECIP. Additional analyses were conducted on non‐affective and schizophrenia spectrum psychoses cases only. Results: There was no overall significant difference in DUP across the three phases. For cases treated within the first year of illness a nonsignificant reduction in DUP to less than 2 months observed during the active phase was sustained post‐ECIP. Conclusion: In some jurisdictions community‐wide early case detection may fail to have an immediate or delayed effect on DUP, especially for cases who normally present for treatment with DUP >1 year.     

Delusional parasitosis in ENT

Otolaryngologists in India often encounter patients with various insects presenting as foreign bodies in the ear and nose. However they overlook the possibility of the clinical entity that has come to be known as delusional parasitosis. Three patients presented in our OPD with this condition and their case reports are discussed.     

(Des-tyr1)-gamma-endorphin (DTγE) in the treatment of depression: Double-blind placebo-controlled trial

Preliminary evidence of a mood-elevating effect for the endogenous neuropeptide, (des-tyr¹)-gamma-endorphin, was further investigated in a double-blind placebo-controlled trial over a period of 2 weeks. There were 10 patients in each group. Between-group comparisons on the change in scores by day 14 were non-significant. There was, however, a significant reduction (p = 0.05, two-tailed) of scores on the Montgomery Asberg Depression Rating Scale and the anxious-depression subscale of the BPRS in the endorphin group. It is recommended that the trial be conducted in a larger sample for definitive results.