Relationship between cortisol, Interleukin-6 and homocysteine in Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) is characterised by progressive cognitive decline due to neurodegeneration. Over activation of the hypothalamic-pituitary-adrenal axis, oxidative stress and inflammation potentially damage the neuronal system, affecting cognition. AIM: This study aimed to assess the relationship between serum cortisol, Interleukin-6 (IL-6) and homocysteine (Hcy) levels in AD. METHODS: Case-Control observational study consisting of 71 patients with AD and 70 healthy controls above 60 years of age. Serum samples were analysed for cortisol, IL-6 and Hcy levels using chemiluminescence immunoassay (Immulite 1000) technique. Cognitive functions were measured using the Mini-Mental State Examination (MMSE) Score. AD subjects were categorised based on the modified Kuppuswamy socioeconomic status scale. Statistical evaluation was conducted using SPSS Statistics software. Group data were analysed using a two-tailed Student's t-test, analysis of variance (ANOVA), the Mann-Whitney U test and Pearson's correlation test. RESULTS: Serum cortisol, IL-6 and Hcy levels were significantly increased (p < 0.01) in AD (cortisol: 19.69 ± 8.96 ug/dl; IL-6: 10.27 ± 2.76 pg/ml; Hcy: 23.29 ± 3.81 µmol/l), as compared with the controls (cortisol: 13.37 ± 5.59 ug/dl; IL-6: 3.37 ± 0.79 pg/ml; Hcy: 8.25 ± 2.36 µmol/l). MMSE scores in AD were negatively correlated with cortisol, IL-6 and Hcy levels. CONCLUSIONS: Serum cortisol, IL-6 and Hcy levels are independent biomarkers for AD progression. Hypercortisolaemia, hyperhomocysteinemia and inflammation play important roles in AD-related cognitive dysfunction and are interlinked.

Assessment of efficacy of palm polymerase chain reaction with microscopy, rapid diagnostic test and conventional polymerase chain reaction for diagnosis of malaria.

Purpose: Sensitive, specific, rapid and cost-effective technique for malaria diagnosis is need of the hour. Microscopy has been the gold standard for malaria diagnosis, but its interpersonnel variability and lack of sensitivity make it subjective test. Conventional polymerase chain reaction (cPCR) has proven to be sensitive technique, but costly and time-consuming. Considering these factors, we have compared microscopy and cPCR with newly derives ultra-fast, portable PCR machine called Palm PCR. Materials and Methods: Palm PCR is arranged with three heat blocks precisely made for three stages of PCR cycles with 34 min for 1100 bp Plasmodium genus outer primer to amplify and 10 min each for Plasmodium falciparum and Plasmodium vivax inner primers of 120 bp and 205 bp, respectively. A total of 191 suspected samples were processed and evaluated using receiver operating characteristic (ROC) curve analysis. Results: The area under ROC curve analysis for Palm PCR with reference standard microscopy for P. falciparum, P. vivax and Plasmodium was 0.8969, 0.9121 and 0.9116, respectively, and with reference standard cPCR was 1.0 for all of them. ROC curve area close of suggests that Palm PCR can be as significant as cPCR in malaria diagnosis. In fact, ultra-rapid amplification with same precision makes Palm PCR better technique than cPCR. Conclusion: Palm PCR is sensitive, rapid and works on battery with simple laboratory facility requirements. Portable electrophoresis and transilluminator combined with Palm PCR could be implemented as an important diagnostic tool in resource-limited and rural areas. Similar studies with wider parameters in rural areas will help us evaluate and maybe establish Palm PCR as PCR platform of choice for such specific set-ups.

Level of suboptimal adherence to first line antiretroviral treatment & its determinants among HIV positive people in India.

BACKGROUND & OBJECTIVES: National Anti-retroviral treatment (ART) programme in India was launched in 2004. Since then, there has been no published country representative estimate of suboptimal adherence among people living with HIV (PLHIV) on first line ART in public settings. Hence a multicentric study was undertaken in 15 States of India to assess the level of suboptimal adherence and its determinants among PLHIV. METHODS: Using a prospective observational study design, 3285 PLHIV were enrolled and followed up to six months across 30 ART centres in India. Adherence was assessed using pill count and self-reported recall method and determinants of suboptimal adherence were explored based on the responses to various issues as perceived by them. RESULTS: Suboptimal adherence was found in 24.5 per cent PLHIV. Determinants of suboptimal adherence were illiteracy (OR--1.341, CI--1.080-1.665), on ART for less than 6 months (OR--1.540, CI--1.280-1.853), male gender (OR for females--0.807, CI--0.662-0.982), tribals (OR--2.246, CI--1.134-4.447), on efavirenz (EFA) regimen (OR--1.479, CI--1.190-1.837), presence of anxiety (OR--1.375, CI--1.117-1.692), non-disclosure of HIV status to family (OR--1.549, CI--1.176-2.039), not motivated for treatment (OR--1.389, CI--1.093-1.756), neglect from friends (OR--1.368, CI--1.069-1.751), frequent change of residence (OR--3.373, CI--2.659-4.278), travel expenses (OR--1.364, CI--1.138-1.649), not meeting the PLHIV volunteer/community care coordinator at the ART center (OR--1.639, CI--1.330-2.019). INTERPRETATION & CONCLUSIONS: To enhance identification of PLHIV vulnerable to suboptimal adherence, the existing checklist to identify the barriers to adherence in the National ART Guidelines needs to be updated based on the study findings. Quality of comprehensive adherence support services needs to be improved coupled with vigilant monitoring of adherence measurement.

Role of thrombomodulin gene in Indian population with coronary artery disease.

CONTEXT: Thrombomodulin (TM), a natural anticoagulant have been implicated in the pathogenesis of coronary artery disease (CAD) thus emphasizing its potential role as a biomarker. OBJECTIVES: To investigate the role of the TM genetic variants and soluble TM (sTM) plasma levels in Indian population with CAD. MATERIALS AND METHODS: This case-control study involved genotyping of the entire TM gene and sTM levels estimation in 266 subjects. RESULTS: None of the four TM genetic variants identified significantly increased CAD risk in the study population. However, further subgroup analysis revealed that in subjects ≤49 years, C1418T variant (Ala455Val substitution) was significantly associated with CAD. CONCLUSION: The increased CAD risk in subjects ≤49 years due to TM Ala455Val substitution is a promising finding. Further validation on large Indian cohorts is required in order to screen asymptomatic young subjects for CAD risk and to establish the clinical utility of Ala455Val substitution.

Correlation of HLA B27 subtypes with clinical features of ankylosing spondylitis.

AIM: The aim of the present study was to identify the B*27 subtypes associated with ankylosing spondylitis (AS) in our population and correlate them with clinical features of AS. METHOD: Whole blood samples were collected from 81 HLA-B27 positive AS patients and 29 controls (asymptomatic healthy unrelated individuals) positive for HLA-B27. Clinical details of the patients were recorded which included history of inflammatory back pain, sacroiliitis, spine involvement, enthesitis, peripheral arthritis and uveitis. HLA-B27 subtypes were detected using commercially available techniques. Fisher's exact test was used for statistical analysis. RESULTS: The subtypes observed in AS patients were B*2705 (67.9%, 55/81), B*2704 (28.4%, 23/81), B*2707 (2/81) and B*2702 (1/81). Subtypes in the controls were B*2705 (62.07%, 18/29), B*2707 (27.59%, 8/29) and B*2704 (10.34%, 3/29). Uveitis was observed more in B*2704-positive AS patients (34.78%, 8/23) compared to B*2705-positive AS patients (16.36%, 9/55). However, the difference was not statistically significant (P = 0.130). No major differences were found between B*2705 and B*2704 for other clinical features. CONCLUSION: B*2705 was the main subtype observed in both patient and control groups. Frequency of B*2704 was more in AS patients compared to controls. Occurrence of AS-associated uveitis was more often in B*2704-positive AS patients compared to B*2705-positive ones.

Prevalence of metabolic syndrome in urban India.

Background. Metabolic syndrome (MS) is characterised by a constellation of individual risk factors of cardiovascular disease. Materials and Methods. The current study was a population-based survey of cohort of subjects in the metropolitan city of Mumbai. A total of 548 subjects, who attended the CARDIAC evaluation camp, were recruited in the study. Participants with complete fasting lipid profiles, blood glucose, and known cardiac risk markers were evaluated. Results. On applying modified NCEP ATP III, we found out that nearly 95% of the subjects had at least one abnormal parameter. We found the prevalence of MS in our study population to be 19.52%. The prevalence of MS in males was almost double than females (P = .008). The overall prevalence of BMI (>23 kg/m(2)) was 79.01%. Increased hypertriglyceridemia and decreased levels of HDL-C were found to be more in males (P < .0001). Conclusion. The low percentage of subjects with normal and controlled parameters suggests that there is a need for awareness programs and lifestyle interventions for the prevention and control of MS.

Prevalence and clinical course of Clostridium difficile infection in a tertiary-care hospital: a retrospective analysis.

The spectrum of Clostridium difficile-associated diarrhea (CDAD) is changing. Apart from antibiotic use, other risk factors such as use of proton pump inhibitors (PPI) and immunosuppressive agents, intensive care unit (ICU) stay and inflammatory bowel disease are being recognized. We retrospectively analyzed data on patients whose stool samples were tested for C. difficile toxin (CDT) by enzyme linked immunosorbent assay between June 2006 and May 2008. Demographic and clinical data, and risk factors (antibiotic use, underlying malignancy, chemotherapy, use of PPI, ICU stay) were noted. The details of treatment for CDAD, response, complication and follow up were recorded. Patients whose stool samples were CDT-positive were grouped as study subjects and those with negative stool samples were included in the control group. Of the 99 patients (mean age 46.7 years; 58 men) whose stool samples were tested during this period, 17 (17%) were positive for CDT. As compared with control subjects (n = 82), study subjects were more likely to have fever, prolonged ICU stay, underlying malignancy, and exposure to immunosuppressive and chemotherapeutic agents. On multivariate analysis, exposure to immunosuppressive agents was the only risk factor associated with CDAD. Fifteen patients were treated with metronidazole and two with vancomycin. Two patients did not respond to metronidazole but responded to vancomycin. No patient developed any complication. The prevalence of C. difficile toxin in diarrheal stools sent for C. difficile toxin testing was 17%. Exposure to immunosuppressive agents was a risk factor for the infection. Metronidazole was effective in a majority of patients.

Transrectal ultrasound-guided prostatic biopsy: midazolam, the ideal analgesic.

OBJECTIVES: Patients with raised serum prostate-specific antigen and/or an abnormal-feeling prostate were subjected to transrectal ultrasound-guided prostatic biopsy to rule out any prostatic malignancy. There are many methods for pain relief and to treat discomfort during the procedure but we compared the efficacy of intravenous (IV) midazolam for pain control. PATIENTS AND METHODS: This was a prospective study of 50 patients. All patients underwent a ten quadrant biopsy. The patients were divided into two groups: group 1 (study group) which included 25 patients who used 1 ml of IV midazolam and group 2 (control group) which included 25 patients who did not use IV midazolam. RESULTS: In group 1, of 25 patients only 1 patient had mild pain (VAS 2) during and after the procedure. In group 2, of 25 patients, 15 patients had pain during the procedure. CONCLUSION: Midazolam is a benzodiazepine derivative with an anxiolytic, sedative, amnestic and hypnotic action. Our study shows that using midazolam is a very simple technique which gives excellent analgesia and no other analgesia was required. No monitoring was needed, there was a very low incidence of complications and it did not require any technical expertise.

A comparative study on the safety and immunogenicity of Purified duck embryo vaccine [corrected] (PDEV, Vaxirab) with purified chick embryo cell vaccine (PCEC, Rabipur) and purifed vero cell rabies vaccine (PVRV, Verorab).

Rabies is a fatal but preventable disease. Cell culture vaccines (CCV) and purified duck embryo vaccines (PDEV) are currently recommended by WHO for post-exposure prophylaxis. In India, a PDEV (Vaxirab) is being manufactured and is in use since 2003. In the present study, we have evaluated the safety, immunogenicity and tolerance of this vaccine with two other WHO approved CCVs, viz., purified chick embryo cell vaccine (PCEC, Rabipur) and purified vero cell rabies vaccine (PVRV, Veroroab). This study was an open label, randomized phase IV comparative clinical trial. A total of 152 people bitten by dogs and other animals were recruited from 4 different centres from India. They were randomly assigned to receive one of the vaccines by Essen intramuscular regimen (52 subjects received Vaxirab and 50 each Rabipur and Verorab) and rabies immunoglobulin was also administered in all category III exposures. Their blood samples were collected on day 0 (prior to vaccination), 14, 28, 90 and 180. Side effects if any were monitored. The rabies neutralizing antibody titers in their blood samples were estimated by the rapid fluorescent focus inhibition test (RFFIT). Subjects in all three groups had neutralizing antibody titers by day 14 (>0.5 IU/mL) and geometric mean titers (GMT) observed for different vaccines on all days tested did not vary significantly (p>0.5). Side effects observed were minimal and did not vary significantly among the groups. The results of the present study indicate that PDEV (Vaxirab) is as safe, tolerable and immunogenic as both PCEC (Rabipur) and PVRV (Verorab). Thus this vaccine can be a good alternative to WHO approved CCVs for rabies post-exposure prophylaxis.