The occurrence of amino acid substitutions D96N and S242N in VP7 of emergent G2P[4] rotaviruses in Nepal in 2004-2005: a global and evolutionary perspective

Rotavirus is the leading cause of severe diarrhea among children worldwide. Strains with G2P[4] have captured recent attention because of its abrupt increase or re-emergence in many locations in the world. In Nepal, G2P[4] strains were detected at a rate of 1% in 2003-2004, but increased to 33% in 2004-2005. Thus, the VP7 genes of 45 emergent G2 strains from Nepal were sequenced and analyzed together with a total of 339 G2VP7 sequences detected over the last 34 years that were compiled from the DNA database. We found that all Nepalese VP7 sequences had a substitution from aspartic acid to asparagine at residue 96 (D96N) that was the hallmark of the lineage termed sublineage IVa, which replaced virtually all globally circulating G2 strains during the last decade. Within sublineage IVa, further sublineages emerged, of which a sublineage termed IVa-3 was identified to have another amino acid substitution from serine to asparagine at 242 (S242N). This sublineage, to which all Nepalese sequences belonged, now became the most frequent G2 sequence globally. In conclusion, the G2VP7 gene evolved in a dynamic fashion such that new lineages emerged within the previously dominant lineage, one of which became subsequently dominant.     

Antihypertensive efficacy of metoprolol XL/Low dose chlorthalidone (6.25 mg) combination: a randomized,comparative study in Indian patients with mild-to-moderate essential hypertension

Objective

High blood pressure is one of the most important risk factors, directly responsible for increasing the cardiovascular morbidity and mortality. The primary objective was to evaluate the efficacy of metoprolol XL/chlorthalidone against metoprolol XL/hydrochlorothiazide with respect to mean fall in systolic and diastolic blood pressure. The secondary objective was to compare the response rates and to evaluate the tolerability of study medications in patients with mild-tomoderate essential hypertension.

Methods

Total 130 eligible patients (65: metoprolol XL 25 mg/chlorthalidone 6.25 mg; 65: metoprolol XL 25 mg/HCTZ 12.5 mg) were enrolled in this randomized, comparative, multicentric, 12-weeks study. Sixty-two patients from each group completed the study. After 4-weeks of treatment, non-responders from chlorthalidone 6.25 mg combination group were shifted to metoprolol XL 50 mg/chlorthalidone 12.5 mg and non-responders from HCTZ 12.5 mg combination group were escalated to metoprolol XL 50 mg/HCTZ 12.5 mg.

Results

The study treatment groups were comparable with respect to demography and baseline disease characteristics. Both the starting therapies were comparable with respect to mean fall in SBP (p = 0.788) and DBP (p = 0.939), and response rates (p = 1.0) after 4-weeks of therapy. Also both the step-up therapies showed similar mean fall in SBP (p = 0.277) and DBP (p = 0.507) at the end of 12-weeks. However, significantly more number of patients from chlorthalidone 12.5 mg/metoprolol XL 50 mg group responded to therapy as compared to that from HCTZ 12.5 mg/metoprolol XL 50 mg group (p = 0.045). All the reported adverse events were of mild-to-moderate intensity. There were no clinically significant trends in electrolytes (Na⁺, K⁺, Cl^-)and fasting blood sugar, evident across the treatment groups.

Conclusion

Chlorthalidone in combination with metoprolol XL is as effective and well tolerated as widely used combination of metoprolol XL/HCTZ, thus providing an alternative therapeutic option.     

Direct medical costs for patients seeking emergency care for losses of epilepsy control in a U.S. managed care setting

The objective of this retrospective claims database study was to compare the costs of care from a U.S. payer perspective before and after epilepsy treatment in emergent care settings and, secondarily, to describe the frequency of toxic effects and physical injuries occurring on the date of the emergent care. Nine and four-tenths percent of patients receiving emergent care for epilepsy (114/1213) had an injury or adverse antiepileptic drug effect on the same date. The majority of incidents were superficial injuries and contusions (28%), fractures (21%), open wounds or injury to blood vessels (19%), intracranial injury (10%), and/or medication toxicity (10%). Both non-epilepsy-related (US$12,745.56) and epilepsy-related (US$2013.62) direct medical costs of care pre-index were significantly different from those post-index (US$15,274.95 and US$7087.53, respectively). The cost of care for possible reestablishment of epilepsy control and treatment of co-occurring injuries is significant when compared with that for the period prior to seizure.     

Infused therapy and survival in older patients diagnosed with metastatic breast cancer who received trastuzumab

We used Surveillance, Epidemiology, and End Results-Medicare data (2000-2006) to describe treatment and survival in women diagnosed with metastatic breast cancer (MBC) who received trastuzumab. There were 610 patients with a mean age of 74 years. Overall, 32% received trastuzumab alone and 47% received trastuzumab plus a taxane. In multivariate analysis, trastuzumab plus chemotherapy was associated with a lower adjusted cancer mortality rate (Hazard Ratio [HR] 0.54; 95% Confidence Interval [CI] 0.39-0.74; p < .001) than trastuzumab alone among patients who received trastuzumab as part of first-line therapy. Adding chemotherapy to first-line trastuzumab for metastatic breast cancer is associated with improved cancer survival.     

Exploring the oral bacterial flora: current status and future directions

Oral Diseases (2010) 16 , 136–145 Objective: The oral cavity forms an indispensable part of the human microbiome, for its unique and diverse microflora distributed within various niches. While majority of these organisms exhibit commensalism, shifts in bacterial community dynamics cause pathological changes within oral cavity and distant sites. The aim of this review was to appraise the current and emerging methods of detecting bacteria of the oral cavity paying particular attention to the cultivation independent methods. Design: Literature pertaining to cultivation based and cultivation independent methods of oral bacterial identification was reviewed. Methods: The specific advantages and disadvantages of cultivation based, microscopic, immunological and metagenomic identification methods were appraised. Results: Because of their fastidious and exacting growth requirements, cultivation based studies grossly underestimate the extent of bacterial diversity in these polymicrobial infections. Culture independent methods deemed more sensitive in identifying difficult to culture and novel bacterial species. Conclusion: Apart from characterizing potentially novel bacterial species, the nucleic acid sequence data analyzed using various bioinformatics protocols have revealed that there are in excess of 700 bacterial species inhabiting the mouth. Moreover, the latest pyrosequencing based methods have further broadened the extent of bacterial diversity in oral niches.     

Does Vitamin D Modulate Asymmetric Dimethylarginine and C-Reactive Protein Concentrations?

Background

Vitamin D deficiency is associated with significant increases in the incidence of cardiovascular risk factors and mortality. However, the mechanisms underlying this association remain unclear. The current study evaluated the possible relationships among vitamin D status, endothelial dysfunction, and inflammation.

Methods

Plasma concentrations of 25-hydroxyvitamin D₃ were determined by radioimmunoassay in a normal population cohort (n = 253) aged 51 to 77 years (mean 63.4 ± 6 years). Asymmetric dimethylarginine, a marker/mediator of endothelial dysfunction, was assayed by high-performance liquid chromatography. High-sensitivity C-reactive protein levels were used as a marker of inflammatory activation.

Results

On univariate analyses, low 25-hydroxyvitamin D₃ levels were inversely correlated with asymmetric dimethylarginine concentrations, high-sensitivity C-reactive protein levels, and body mass index. Seasonal fluctuations in 25-hydroxyvitamin D₃ levels were associated with reciprocal asymmetric dimethylarginine concentration fluctuations. Hypertension and treatment with an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker also were associated with low 25-hydroxyvitamin D₃ levels. On multiple linear analysis, both asymmetric dimethylarginine (β = −0.19, P = .003) and high-sensitivity C-reactive protein (β = −0.14, P = .03) concentrations were inversely correlated with plasma 25-hydroxyvitamin D₃ concentrations; other significant correlates were male gender (β = 0.19, P = .003), calcium levels (β = 0.14, P = .03), and use of angiotensin-converting enzyme inhibitor (β = −0.17, P = .007).

Conclusion

Low 25-hydroxyvitamin D₃ levels are associated with markers of endothelial dysfunction and inflammatory activation, representing potential mechanisms for incremental coronary risk.     

Recombinant factor VIIa for intraoperative bleeding in a child with hepatoblastoma and review of recombinant activated factor VIIa use in children undergoing surgery

We report a case of a child with a large liver mass who underwent an open liver biopsy and had massive bleeding intraoperatively. Recombinant activated factor VII (rFVIIa) given intraoperatively was successful in stopping the bleeding. We also reviewed the literature on the use of rFVIIa in pediatric surgery.