Syntheses and bioevaluation of substituted dihydropyridines for pregnancy-interceptive activity in hamsters

A number of 2,6-dimethyl-3,5-bis(methoxycarbonyl)-4-substituted-1,4- dihydropyridines were synthesized and evaluated for pregnancy-interceptive activity in mated hamsters. Out of 24 compounds, 12, 15, 21, 22, 28, and 34 caused a marked reduction in the number of implantations when administered on days 3-8 postcoitum. In an in vitro competition assay, none of the compounds exhibited noticeable binding affinity for uterine progesterone receptors. The results reported here have helped to identify new leads for developing pregnancy-interceptive agents and the active compounds do not seem to elicit their interceptive effect through receptor-mediated inhibition of progesterone action in hamster uterus.     

Acute renal failure due to rifampicin

A 23-year-old male patient with bacteriologically proven pulmonary tuberculosis was treated with the various regimens of antituberculosis drugs for nearly 15 months. Rifampicin was administered thrice as one of the 3-4 drug regimen and each time he developed untoward side effects like nausea, vomiting and fever with chills and rigors. The last such episode was of acute renal failure at which stage the patient was seen by the authors of this report. The patient, however, made a full recovery.     

Safety and efficacy of the argatroban therapy during the early post-cardiac surgery period

Heparin-induced thrombocytopenia (HIT) is associated with a high incidence of vein graft occlusion after cardiac surgery. When HIT is suspected during the post-operative period, current guideline recommends a direct thrombin inhibitor such as argatroban to be started immediately. The aim of this retrospective study was to evaluate the safety and efficacy of argatroban in the early period after cardiac surgery. All patients who received argatroban within 72 h after cardiac surgery from September 2005 to June 2009 from a single center were included. Patient demographics, pre-operative relevant history, intra-operative events and post-operative data were collected and analyzed. The primary endpoints were bleeding, thrombotic complication during or after argatroban administration, and in-hospital mortality. The study population comprised 31 patients administered argatroban within 72 h after cardiac surgery. Argatroban was started a mean of 1.7 days after surgery (median dose, 0.66 μg/kg/min; median duration, 5.9 days). Twenty patients (64.5%) experienced bleeding; episode driven entirely by the need for blood transfusion. No new thromboembolic complication occurred during or after argatroban infusion. One patient died from aspiration pneumonia. Compared to those without bleeding complications, patients who bled had longer operation times and increased use of intra-aortic balloon pump. However, argatroban therapy including the starting time, median dose, infusion duration, and activated partial thromboplastin times showed no difference between the two groups. In cardiac surgery patients with clinical suspicion of HIT, early postoperative use of argatroban seems well-tolerated and associated with a low risk of thrombotic events.     

Impact of cardiac intraoperative precursor events on adverse outcomes

BACKGROUND: Although extensive study has been directed at the influence of patient factors and comorbidities on cardiac surgical outcomes, less attention has been focused on process. We sought to examine the relationship between intraoperative precursor events (those events that precede and are requisite for the occurrence of an adverse event) and adverse outcomes themselves. METHODS: Anonymous, prospectively collected intraoperative data was merged with database outcomes for 450 patients undergoing major adult cardiac operations. Precursor events were categorized by type, person most affected, severity, and compensation. Number and categories of precursor events were analyzed as predictors of a composite outcome combining death or near miss complications (DNM), using logistic regression. RESULTS: Precursor events occurred more frequently in cases with a DNM outcome than in those with no adverse event (2.7 +/- 2.4 vs 2.0 +/- 2.3/procedure, P = .005). After adjustment for other patient characteristics, the number of precursor events remained an independent predictor of DNM (RR, 1.14 per event [1.04 to 1.24]). Of 990 events, 35.6% related to management, 28.8% were technical, and 22.8% were environment-related. The surgeon was most affected in 40.8%, and 16.5% were of major severity. When categories of precursor events were analyzed, major severity events and those most affecting the surgeon were independent predictors of DNM. CONCLUSIONS: More detailed study of process in complex operations may lead to improved quality of care and patient safety. Special attention must be paid particularly to high risk patients and high risk precursor events.     

Autonomic neuropathy as post-acute sequela of SARS-CoV-2 infection: a case report

Journal of NeuroVirology - Symptoms of autonomic dysfunction, particularly those of orthostatic intolerance, continue to represent a major component of the currently recognized post-acute sequelae...     

Subtype B and subtype C HIV type 1 recombinants in the northeastern state of Manipur, India

The predominant HIV-1 strain circulating in India is subtype C. However, subtype A and B strains of HIV-1 have also been reported in India. In 1999, the first A/C recombinant strain was reported from Pune in India. Intravenous drug users (IVDUs) from the northeastern region of India have a high HIV-1 seroprevalence. Studies carried out in intravenous drug users in the northeastern region of India have shown that HIV-1 subtype C is the predominant strain infecting IVDUs. Fourteen blood samples were collected from HIV-1-infected individuals from the northeastern region of India and screened by env and gag heteroduplex mobility assays (HMA). Where the env and gag HMA results from a sample yielded different subtypes, sequencing of env and gag PCR products was carried out to confirm the presence of HIV-1 recombinants. Of the 14 samples subtyped, nine samples belonged HIV-1 subtype C (gag C/env C), one to HIV-1 subtype B (gag B/env B), and the remaining were B/C recombinants (gag C/env B). This is the first report of HIV-1 B/C recombinants from India.     

The long-term stability of new hippocampal place fields requires new protein synthesis

The hippocampus is critical for formation of spatial memories. Hippocampal pyramidal neurons in freely behaving animals exhibit spatially selective firing patterns, which taken together form an internal representation of the environment. This representation is thought to contribute to the hippocampal spatial memory system. Behavioral long-term memories differ from short-term memories in requiring the synthesis of new proteins. Does the development of the internal hippocampal representation also require the synthesis of new proteins? We found that blocking protein synthesis in the brain of mice by 95% does not affect short-term stability of newly formed hippocampal place fields but abolishes stability in the long term. By contrast, inhibiting protein synthesis does not affect the retention and recall of previously established fields in a familiar environment, indicating that protein synthesis-dependent reconsolidation is not required for recall. Our results indicate that place fields parallel both behavioral memories and the late phase of long-term potentiation in requiring the synthesis of new proteins for consolidation.     

The use of cardiopulmonary bypass during resection of locally advanced thoracic malignancies: a 10-year two-center experience

The use of cardiopulmonary bypass (CPB) for locally advanced thoracic malignancies is highly controversial. The purpose of this study was to document the techniques and results of CPB to facilitate the resection of complex thoracic malignancies and to identify common themes that provided for successful outcomes. This was a retrospective study that took place from January 1992 to September 2002. Fourteen consecutive patients (median age, 59 years; age range, 18 to 69 years; seven men and seven women) underwent CPB during the resection of locally advanced thoracic malignancies at two Boston hospitals. CPB was planned in 8 of 14 patients (57%) with centrally located tumors, while 6 of 14 patients (43%) required emergent institution of CPB due to injury of the superior vena cava (2 patients), inferior vena cava (2 patients), or pulmonary artery (2 patients). Complete microscopic resection was achieved in 12 of 14 patients (86%). The operative mortality rate was 1 of 14 patients (7%) due to pulmonary embolism (ie, the elective group). The median ICU and hospital lengths of stay were 5 and 9 days, respectively. The overall 1-year, 3-year, and 5-year survival rates were 57%, 36%, and 21%, respectively. The planned use of CPB to facilitate complete resection of thoracic malignancies should be considered only after careful patient selection. The availability of CPB also provides a safety net in the event of injury to vascular structures during tumor resection.     

Childhood adherence to a potentially healthy and sustainable Nordic diet and later overweight: The Norwegian Mother,Father and Child Cohort Study (MoBa)

The New Nordic Diet (NND) is a potentially healthy and sustainable dietary pattern represented by locally available and traditionally consumed foods in the Northern countries. The diet has been commonly examined in adult populations, but less is known regarding its potential associations with overweight/obesity in children. We have previously developed child diet scores measuring compliance to the NND at child age 6 and 18 months and 3 and 7 years. In this study, we aimed to describe child and maternal characteristics and assess potential associations between the age‐specific diet scores and child overweight at 8 years. This study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa), including 14,989 mother–child pairs and uses data from the Medical Birth Registry of Norway (MBRN). The scores measured NND compliance as a total score and categorized into low, medium and high NND compliance at each age point. Using logistic regression models, we investigated the association between each age‐specific score and the odds of overweight at 8 years. In crude analyses, adherence to the NND at 6 months was inversely associated with odds of overweight at 8 years in the continuous score (odds ratio = 0.95, 95% CI [0.91, 0.98]) and when comparing high versus low NND adherence (odds ratio = 0.81, 95% CI [0.70, 0.94]). The association was almost entirely attenuated in the adjusted models. In conclusion, child NND adherence up to 7 years of age was not associated with odds of overweight at 8 years in adjusted analyses.