NAT positivity in seronegative voluntary blood donors from western India

Background and objectives

Prevalence and composition of Hepatitis B, Hepatitis C and HIV-1, NAT positive but seronegative voluntary blood donors from western part of India is yet to be documented.

Response to zolendronic acid in children with type III osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a common genetic disorder that manifests with intrauterine or pre- or postnatal fractures, blue sclera, and deafness. Various treatments for the management of OI have been tried, of which bisphosphonates (BPs) seem to have the maximum benefit in reducing fracture rate and improving bone density. Zolendronic acid is a newer BP tried for several bone diseases, mainly in adults. The objective of our analysis was to study the response to zolendronic acid in children with type III OI. The case records of subjects with type III OI receiving zolendronic acid in the past 3 years between February 2006 and March 2009 were analyzed. Relevant details were recorded on a predesigned chart. Subjective improvement, reduction in number of fractures, and the DEXA scan Z-score were used to judge improvement. Five OI type III cases were followed up in the Genetic clinic. Presentation was from neonatal period to 7 years of age; M:F ratio was 3:2. Average duration of therapy given was 20.4 months. Improvement was noted in all patients, in the form of reduction in frequency of fractures (P = 0.002) and increase in bone density on DEXA scan (P = 0.01). Side effects noted were flu-like symptoms and myalgia. No clinical problems due to hypocalcemia were noted in any of the patients. Thus, zolendronic acid is seen as a safe and effective BP in type III OI children. The exact dose for optimal benefit is yet to be determined. The long-term effects of newer BPs need further long-term trials.     

Aberrant expression of the polarity complex atypical PKC and non-muscle myosin IIA in active and inactive inflammatory bowel disease

Epithelial barrier function is contingent on appropriate polarization of key protein components. Work in intestinal epithelial cell cultures and animal models of bowel inflammation suggested that atypical PKC (aPKC), the kinase component of the Par3–Par6 polarity complex, is downregulated by pro-inflammatory signaling. Data from other laboratories showed the participation of myosin light chain kinase in intestinal inflammation, but there is paucity of evidence for assembly of its major target, non-muscle myosin II, in inflammatory bowel disease (IBD). In addition, we showed before that non-muscle myosin IIA (nmMyoIIA) is upregulated in intestinal inflammation in mice and TNFα-treated Caco-2 cells. Thus far, it is unknown if a similar phenomena occur in patients with IBD. Moreover, it is unclear whether aPKC downregulation is directly correlated with local mucosal inflammation or occurs in uninvolved areas. Frozen sections from colonoscopy material were stained for immunofluorescence with extensively validated specific antibodies against phosphorylated aPKC turn motif (active form) and nmMyoIIA. Inflammation was scored for the local area from where the material was obtained. We found a significant negative correlation between the expression of active aPKC and local inflammation, and a significant increase in the apical expression of nmMyoIIA in surface colon epithelia in inflamed areas, but not in non-inflamed mucosa even in the same patients. Changes in aPKC and nmMyoIIA expression are likely to participate in the pathogenesis of epithelial barrier function in response to local pro-inflammatory signals. These results provide a rationale for pursuing mechanistic studies on the regulation of these proteins.     

Perilipin deficiency and autosomal dominant partial lipodystrophy

Perilipin is the most abundant adipocyte-specific protein that coats lipid droplets, and it is required for optimal lipid incorporation and release from the droplet. We identified two heterozygous frameshift mutations in the perilipin gene (PLIN1) in three families with partial lipodystrophy, severe dyslipidemia, and insulin-resistant diabetes. Subcutaneous fat from the patients was characterized by smaller-than-normal adipocytes, macrophage infiltration, and fibrosis. In contrast to wild-type perilipin, mutant forms of the protein failed to increase triglyceride accumulation when expressed heterologously in preadipocytes. These findings define a novel dominant form of inherited lipodystrophy and highlight the serious metabolic consequences of a primary defect in the formation of lipid droplets in adipose tissue.     

Amiodarone therapy for atrial rhythm control: insights gained from a single center experience

Introduction: Amiodarone has been advocated as an effective "long-term" therapy for atrial rhythm control in patients with atrial fibrillation (AF). We sought to assess the sustainability of this therapeutic strategy.
Methods and Results: Retrospective analysis of a consecutive, single-center cohort (n = 168) with symptomatic AF who were treated with amiodarone and followed for 3 years. The incidence of amiodarone cessation was evaluated at 1, 2, and 3 years and attributed principally to drug inefficacy, intolerance, or toxicity. A gradual diminution in the number of patients on therapy was observed, such that by 3 years, only 45% remained. This was attributable to inefficacy (25%), intolerance (12%), or toxicity (18%). Pulmonary toxicity was surprisingly common, occurring in at least 7% of patients.
Conclusions: These data challenge the notion of amiodarone as a reasonable "destination" therapy for AF.     

Development of atropine sulphate nasal drops and its pharmacokinetic and safety evaluation in healthy human volunteers

IntroductionThe increased use of organophosphate (OP) insecticides and the ever increasing possibility of terror groups using nerve agents underscore the need to develop effective and safe antidotes against OP poisoning. While intramuscular administration of nerve gas antidotes like atropine sulphate has certain lacunae, intravenous route is neither practical nor feasible in the field conditions for mass casualties. The objective was to develop a novel atropine sulphate nasal drop formulation, evaluate and characterize it using scintigraphy and to carry out safety–efficacy study in human volunteers with a view to obtain early pharmacological effects in comparison to the existing options, particularly the conventional intramuscular route.MethodsPermeability studies were done using atropine sulphate solution containing variable amount of chitosan. Radiometric method was developed for scintigraphy studies while standard spectroscopy was used for the quantification of atropine sulphate in fluids. Concentration of atropine sulphate in nasal drops to produce therapeutic concentration in blood was calculated. Six volunteers (age range 18–53 years) were administered the formulation delivering 6 mg of atropine sulphate each. Bioavailability and atropinization were noted serially.ResultsBased on the results of in vitro, human scintigraphy and analytical data, 1% atropine sulphate–0.5% chitosan was chosen as the final nasal formulation. Human bioavailability curve was created which showed that the therapeutic concentration of the drug in blood was reached within 5 min with nasal drops suggesting that drug delivery through the nasal route is significantly better than the intramuscular route. Unpaired t-test between the means of baseline value of heart rate and that of each time interval showed that increase in heart rate of all the volunteers became significant at 15 min (P < 0.01) and extremely significant at 30 min (P < 0.001). Correlation was evident from 5 min (c > 0.7). Pupil diameter showed maximal increase at 30 min (P < 0.01).ConclusionsThis novel product, 1% atropine sulphate–0.5% chitosan nasal drops might be a safe and efficacious emergency treatment of organophosphorous poisoning with several advantages over the present management, including early atropinization and capability of mass treatment in least amount of time.     

Simultaneous spectrophotometric estimation of Hydrochlorothiazide, Atenolol and Losartan potassium in tablet dosage form

Two simple, accurate and reproducible spectrophotometric methods have been developed for the simultaneous estimation of Hydrochlorothiazide (Hctz), Atenolol (Atn) and Losartan potassium (Los) in combined tablet dosage forms. The first method involves determination using the simultaneous equation method, the sampling wavelengths selected are, 272.5 nm, 224 nm and 250 nm over the concentration ranges of 0.5-30 microg/ml, 1-50 microg/ ml and 1-60 microg/ml for Hctz, Atn and Los respectively. The second method is the First order derivative method, the sampling wavelengths selected for estimation of Hctz, Atn and Los are 280.5 nm, 233 nm and 244 nm with linearity in the concentration ranges of 0.5-30 microg/ ml, 1-50 microg/ml and 1-60 microg/ml respectively. The results of the analysis were validated statistically and recovery studies were carried out as per ICH guidelines.     

The cisterna chyli: enhancement on delayed phase MR images after intravenous administration of gadolinium chelate

PURPOSE: To retrospectively evaluate cisterna chyli (CC) enhancement on magnetic resonance (MR) images obtained after intravenous administration of a gadolinium-based contrast agent. MATERIALS AND METHODS: This retrospective HIPAA-compliant study of 1.5-T MR imaging findings was institutional review board approved; informed patient consent was waived. All MR examinations involved the acquisition of heavily T2-weighted single-shot fast spin-echo (SSFSE) images and three-dimensional (3D) gradient-echo images obtained before and during the arterial, venous, and 3-5-minute delayed phases after intravenous bolus injection of gadopentetate dimeglumine. Included were the data of 59 patients (37 men, 22 women; mean age, 59 years) who had a CC 4 mm or greater in transverse diameter, which was identified as a tubular structure with fluid signal intensity (SI) on SSFSE images. The SI of the CC relative to the spinal canal (SC) was noted and was measured on 3D gradient-echo images obtained during all phases. The Student t test was performed for statistical evaluations. RESULTS: Mean CC-SC SI ratios on nonenhanced, arterial phase, venous phase, and delayed phase images were 0.92, 0.98, 0.99, and 2.13, respectively. The CC had low SI on all 3D gradient-echo images obtained during the nonenhanced, arterial, and venous phases and high SI, similar to the azygos vein SI, on all delayed phase images. The CC-SC SI ratio during the delayed phase was significantly higher than that during the other phases (P<.001). CONCLUSION: The CC has minimal or no enhancement on arterial phase and venous phase images but intense enhancement--similar to the enhancement of veins--on delayed phase images. Comparison of delayed phase images with SSFSE and venous phase images may help to distinguish the CC seen on delayed phase images from lymph nodes, the azygos vein, or esophageal varices.     

Reasons and outcomes of laparoscopic revisional surgery after laparoscopic adjustable gastric banding for morbid obesity

BackgroundLaparoscopic adjustable gastric banding (LAGB) is a purely restrictive procedure that has been proved to be an effective tool in achieving weight loss. The low operative morbidity and reversibility are often seen as advantages of this procedure compared with other bariatric approaches. We have attempted to define the reasons for revisional surgery after LAGB and the outcomes.MethodsA retrospective review of a prospectively maintained database was performed from February 2001 to October 2008 at a center of excellence after institutional review board approval. The patients who had undergone revisional surgery after primary LAGB were evaluated.ResultsOf 343 patients who had undergone primary LAGB, 60 subsequently underwent a revisional procedure. In addition, 28 revisional procedures were performed on patients who had undergone primary LAGB at an outside institution. These procedures included 39 (44.3%) band removals alone, 12 (13.6%) band removals with conversion to sleeve gastrectomy, 13 (14.8%) band removals with conversion to Roux-en-Y gastric bypass, 9 (10.2%) band repositioning, and 2 (2.3%) band replacements. In addition, 13 (14.8%) port-related procedures (3 relocations, 6 reconnections, and 4 replacements/removals) were performed.ConclusionAlthough reversible and efficacious, LAGB appears to have a high incidence of complications requiring revisional surgery and/or band removal. The results of our study have shown that laparoscopic revisional surgery after primary LAGB is safe and can be performed with minimal morbidity.