An atomic resolution description of folic acid using solid state NMR measurements

The chemical shift anisotropy tensor and site-specific spin-lattice relaxation time of folic acid were determined by a ¹³C 2DPASS CP-MAS NMR experiment and Torchia CP experiment respectively. The molecular correlation time at various carbon nuclei sites of folic acid was evaluated by assuming that the ¹³C spin-lattice relaxation mechanism is mainly governed by chemical shift anisotropy interaction and hetero-nuclear dipole–dipole coupling. CSA parameters are larger for the carbon nuclei residing at the heteroaromatic ring and aromatic ring, and those attached to double-bonded electronegative oxygen atoms. It is comparatively low for C9, C19, C21, and C22. The molecular correlation time is of the order of 10⁻⁴/10⁻⁵ s for C9, C19, C21 and C22 carbon nuclei, whereas it is of the order of 10⁻³ s for the rest of the carbon nuclei sites. Spin lattice relaxation time varies from 416 s to 816 s. For C23 and C14, the value is 816 s, and it is 416 s for C7 nuclei. The correlation between structure and dynamics on an atomic scale of such an important drug as folic acid can be visualized by these types of extensive spectroscopic measurements, which will help to develop an advanced drug for DNA replication.

The chemical shift anisotropy tensor and site specific spin-lattice relaxation time of folic acid were determined by a ¹³C 2DPASS CP-MAS NMR experiment and Torchia CP experiment respectively.     

Effectiveness of thoracoscopic truncal vagotomy in the treatment of marginal ulcers after laparoscopic Roux-en-Y gastric bypass

Marginal ulcer is a significant complication of laparoscopic Roux-en-Y gastric bypass (LRYGB). Most marginal ulcers resolve with medical management, but nonhealing ulcers may require revision of the gastrojejunostomy, a procedure with significant morbidity and mortality. Traditionally, surgical therapy for refractory peptic ulcers includes a vagotomy. The current study evaluates the effectiveness of thoracoscopic truncal vagotomy (TTV) in the management of refractory marginal ulcers. All patients at two institutions with an intractable marginal ulcer after LRYGB treated with TTV between 2003 and 2010 were reviewed. Data were collected from chart review and telephone interview. Seventeen patients (mean age, 39 ± 13 years; 16 females) were diagnosed with marginal ulceration a median of 18 months after LRYGB and proceeded to TTV at a mean of 39 ± 43 weeks (range, 1 to 114 weeks) after the diagnosis. The median operative time was 89 ± 65 minutes (range, 45 to 318 minutes). Four patients had a complication (sympathetic contralateral pleural effusion, pneumothorax, operative bleeding, and readmission for emesis). Eleven patients had follow-up of 3 months to 6 years (median, 7 months). Nine patients (82%) had symptomatic improvement and/or endoscopic resolution, whereas two (18%) did not. No patient had endoscopic evidence of persistent or recurrent marginal ulcer. TTV achieves symptomatic improvement and/or endoscopic resolution of intractable marginal ulcers in over 80 per cent of patients status post gastric bypass and therefore offers a less morbid alternative to revision of the gastrojejunostomy.     

Clinical,Immunological, and Molecular Findings of Patients with p47<Superscript>phox</Superscript> Defect Chronic Granulomatous Disease (CGD) in Indian Families

Chronic granulomatous disease (CGD) is a group of inherited disorder of phagocytes, resulting from mutations in the components of the NADPH oxidase complex. Reduced or absent oxygen radical synthesis seen in these patients leads to impaired killing of intracellular bacteria and fungi. CGD clinically presents with recurrent and life-threatening infections as well as granulomatous inflammatory responses. p47^phox encoded by the NCF1 gene is the most common autosomal recessive form of CGD which is often clinically milder. Here, we are presenting the data on clinical and immunological findings in 21 Indian patients with Del GT mutation in the NCF1 gene. Diagnosis of these patients was based on detailed clinical evaluation, measurement of respiratory burst activity by nitro blue tetrazolium and dihydrorhodamine-1,2,3 assay, expression of p47^phox by flow cytometry, and molecular confirmation by GeneScan method. Seventeen male and four female patients with median age of onset of 1 year ranging from 1.5 months to 6 years were included in the study. Sixty-two percent (13 out of 21) of patients belonged to a consanguineous marriage with only one family having a history of a previous sibling death. Significant variability in clinical presentation was observed in spite of identical genetic defect ranging from asymptomatic to very severe presentation leading to early death or requiring transplantation. However, none of these patients showed difference in immunological parameters to account for this variability. Thus, this study highlights the phenotypic heterogeneity seen in these patients with Del GT mutation in the NCF1 gene and its implication in management of these patients.     

Physical injury: a profile among the municipal primary school children of Siliguri, Darjeeling District

A cross sectional study was conducted from February - May 2009 with the objectives to find out profile of injuries among municipal primary school children in Siliguri, West Bengal and to identify the related factor associated with injury. 20% of total primary schools under municipal corporation of the town were selected and a pre-designed, pre-tested schedule was used to assess the profile of injury and associated factors. The Chi square test was usedto determine statistical significance at the 0.05 significance level. Out of 956 participants, a significantly higher injury was observed among males (68%). Open wound injuries were commonest (59.6%) occurring mainly at the extremities. Falls were mainly responsible for overall injuries. Injury at home (41.8%) was also found to be more. Mother education, number of siblings and presence of caregiver were significant related factors to injury.     

A comparative study of oral tramadol and ibuprofen in postoperative pain in operations of lower abdomen

The objective of this study was to assess efficacy and safety of oral tramadol in postoperative pain in operations of lower abdomen as compared to oral ibuprofen. Eighty patients undergoing operations in the lower abdomen under spinal anaesthesia were randomly assigned to two parallel groups--ibuprofen 400 mg thrice daily and tramadol 100 mg thrice daily, both orally after food. Treatment was given single-blind for 5 days in the postoperative period. Patient's perception of pain scored byvisual analogue scale (VAS) and wound tenderness assessed by a 3-point ordinal scale were the primary efficacy parameters. A steady decline in VAS pain score from baseline to study end (99.7 +/- 2.75 to 54.4 +/- 9.71 in the ibuprofen group and 97.3 +/- 3.14 to 52.5 +/- 9.95 in tramadol group) indicated good analgesic efficacy in both groups. Within groups, comparisons showed highly significant difference in VAS score between baseline and each of the subsequent assessment time points (p < 0.001). Between groups differences were not significant at any point. There were no intergroup differences in wound tenderness at baseline or at study end. Rescue medication was needed by 6 subjects on ibuprofen but none on tramadol (p = 0.011). Both regimens were well tolerated. It can be thus concluded that oral tramadol is safe, effective and comparable to ibuprofen as analgesic for relieving pain in the postoperative period in patients undergoing operations in the lower abdomen. The need for rescue medication for breakthrough pain may be less with tramadol.     

Nutritional effect of oral supplement enriched in beta-hydroxy-beta-methylbutyrate, glutamine and arginine on resting metabolic rate after laparoscopic gastric bypass

Background  

Weight regain that begins 12–18 months after laparoscopic gastric bypass has been attributed to changes in resting metabolic rate (RMR), which is largely determined by lean body mass (LBM). An oral supplement containing beta-hydroxy-beta-methylbutyrate, glutamine, and arginine (HMB/Glu/Arg) has helped to restore LBM in cachexia due to cancer and in critically ill trauma patients. The objective of this study was to evaluate the effect of oral HMB/Glu/Arg on LBM and RMR following laparoscopic gastric bypass (LGB).     

Patient-centered medical homes in the United States

The concept of a medical home is receiving increased attention as a potential means to improve care and reduce costs. This study describes the characteristics and capabilities of practices that have achieved recognition of National Committee for Quality Assurance as a "patient-centered medical home" (PCMH). Both small and large practices demonstrate capabilities related to the goals of PCMH of accessible, coordinated, and patient-centered care; however, practices affiliated with larger organizations achieve higher levels of PCMH recognition compared with unaffiliated small practices. Efforts to support practices to implement medical home capabilities are needed, particularly in the use of data for population management and patient self-management.     

The therapeutic potential of targeting endogenous inhibitors of nitric oxide synthesis

Asymmetric dimethylarginine (ADMA)--a naturally occurring amino acid that is a product of protein breakdown--is released into the cytoplasm following the post-translational methylation of arginine residues within proteins and the subsequent proteolysis of these arginine-methylated proteins. ADMA inhibits all three isoforms of nitric oxide synthase and therefore has the potential to produce diverse biological effects, particularly in the cardiovascular system. In addition to its renal clearance, endogenously produced ADMA is metabolized to L-citrulline and dimethylamine by the dimethylarginine dimethylaminohydrolase (DDAH) enzymes. Pharmacological modification of DDAH has therefore been proposed as a mechanism for manipulating endogenous ADMA concentrations and regulating the production of nitric oxide in situations where alterations in nitric oxide signalling have been shown to contribute to pathophysiology. This review describes the biology of ADMA and the potential therapeutic utility of manipulating DDAH activity.     

A double-blind, placebo-controlled pilot study of quetiapine for depressed adolescents with bipolar disorder

Objective: To conduct a pilot study comparing the effects of quetiapine and placebo for the treatment of depressive episodes in adolescents with bipolar I disorder. Method: Thirty‐two adolescents (ages 12–18 years) with a depressive episode associated with bipolar I disorder were randomized to eight weeks of double‐blind treatment with quetiapine, 300–600 mg/day, or placebo. This two‐site study was conducted from March 2006 through August 2007. The primary efficacy measure was change in Children’s Depression Rating Scale–Revised Version (CDRS‐R) scores from baseline to endpoint. Secondary efficacy measures included change in CDRS‐R scores over the eight‐week study period (PROC MIXED), changes from baseline to endpoint in Hamilton Anxiety Rating Scale (HAM‐A), Young Mania Rating Scale (YMRS), and Clinical Global Impression–Bipolar Version Severity (CGI‐BP‐S) scores, as well as response and remission rates. Safety and tolerability were assessed weekly. Results: There was no statistically significant treatment group difference in change in CDRS‐R scores from baseline to endpoint (p = 0.89, effect size =?0.05, 95% confidence interval: ?0.77–0.68), nor in the average rate of change over the eight weeks of the study (p = 0.95). Additionally, there were no statistically significant differences in response (placebo =67% versus quetiapine = 71%) or remission (placebo = 40% versus quetiapine = 35%) rates, or change in HAM‐A, YMRS, or CGI‐BP‐S scores (all p > 0.7) between treatment groups. Dizziness was more commonly reported in the quetiapine (41%) than in the placebo (7%) group (Fisher’s exact test, p = 0.04). Conclusions: The results suggest that quetiapine monotherapy is no more effective than placebo for the treatment of depression in adolescents with bipolar disorder. However, limitations of the study, including the high placebo response rate, may have contributed to our findings and should be considered in the design of future investigations of pharmacological interventions for this population.