Persistent rat cytomegalovirus (RCMV) infection of the salivary glands contributes to the anti-RCMV humoral immune response

The salivary glands are the major sites of persistent replication of rat cytomegalovirus (RCMV). At several months post infection (pi), infectious RCMV is usually still produced in the salivary glands but not in any other organ or tissue of the rat. To investigate whether the persistence of RCMV in the salivary glands is crucial to the pathogenesis of viral infection, we monitored the progression of RCMV-induced disease in rats from which the salivary glands had been surgically removed (desalivated) as well as in sham-operated rats, both after a lethal and sublethal challenge with RCMV. Desalivation did not have a significant effect on either RCMV-induced morbidity or mortality. As expected, at 1 year pi, relatively high levels of infectious virus were detected in the salivary glands of sham-operated rats, whereas neither infectious virus nor RCMV DNA could be detected in liver, spleen and lungs of these animals. Infectious virus and viral DNA were also undetectable in organs from desalivated animals at 1 year pi. Surprisingly, a difference was found between desalivated and sham-operated rats in the titers of anti-RCMV IgG antibodies, which were significantly higher in sham-operated rats than in desalivated animals at 183, 295 and 365 days pi. This finding indicates that the persistence of RCMV in the salivary glands may contribute significantly to the anti-RCMV humoral immunity of infected rats.     

Patients' perceptions of outcomes of a Canadian hospitalization

Notes that with health care reform moving at tremendous speed throughout Canada, a great deal of interest in outcomes research has been generated. States that the research team consisted of 17 professional practice leaders from eight disciplines. Proposes, through the research, to identify from the perspective of former patients what results they hoped to achieve prior to discharge from hospital and what facilitated and hindered them in achieving these results. Reports that a representative sample was selected for the study. Forty-one former patients each participated in up to two focus groups, with a total of 16 focus groups conducted. Hierarchical analysis revealed themes that fell within the framework of structure, process and outcomes. The findings will assist in ensuring that more appropriate and effective care is offered to patients by a variety of disciplines.     

Maternal death reviews at a rural hospital in Malawi

ObjectiveTo analyze maternal deaths at Nkhoma Church of Central Africa Presbyterian (CCAP) Hospital and identify factors causing delays in care.MethodsMaternal death audits are performed after every maternal death at Nkhoma CCAP Hospital. Information regarding the care provided at the health facility, the referral process, and any delays in the community was collected by an audit team using a structured approach. Data from August 2007 to September 2011 were analyzed retrospectively.ResultsIn total, 61 maternal deaths occurred during the study period, of which 58 were analyzed. Most deaths were categorized as indirect (n = 34 [58.6%]). Non-pregnancy-related infections were the leading cause of indirect death (n = 22), with meningitis the most common (n = 13). Most patients experienced a delay in seeking care (n = 37 [63.8%]), a transport delay (n = 43 [74.1%]), or a delay in receiving adequate care (n = 34 [58.6%]).ConclusionMost maternal deaths had indirect causes and were associated with delays in all phases. An audit makes clear which part of the referral chain needs to be strengthened. Nkhoma CCAP Hospital has taken steps to address all phases of delay.     

Sandwich corrected standard errors in family-based genome-wide association studies

Given the availability of genotype and phenotype data collected in family members, the question arises which estimator ensures the most optimal use of such data in genome-wide scans. Using simulations, we compared the Unweighted Least Squares (ULS) and Maximum Likelihood (ML) procedures. The former is implemented in Plink and uses a sandwich correction to correct the standard errors for model misspecification of ignoring the clustering. The latter is implemented by fast linear mixed procedures and models explicitly the familial resemblance. However, as it commits to a background model limited to additive genetic and unshared environmental effects, it employs a misspecified model for traits with a shared environmental component. We considered the performance of the two procedures in terms of type I and type II error rates, with correct and incorrect model specification in ML. For traits characterized by moderate to large familial resemblance, using an ML procedure with a correctly specified model for the conditional familial covariance matrix should be the strategy of choice. The potential loss in power encountered by the sandwich corrected ULS procedure does not outweigh its computational convenience. Furthermore, the ML procedure was quite robust under model misspecification in the simulated settings and appreciably more powerful than the sandwich corrected ULS procedure. However, to correct for the effects of model misspecification in ML in circumstances other than those considered here, we propose to use a sandwich correction. We show that the sandwich correction can be formulated in terms of the fast ML method.     

Amiodarone versus sotalol for the treatment of atrial fibrillation after open heart surgery: the Reduction in Postoperative Cardiovascular Arrhythmic Events (REDUCE) trial

Objectives

This prospective, randomized, double-blind, placebo-controlled study compared the efficacy and safety of amiodarone and sotalol in the prevention of atrial fibrillation (AF) following open heart surgery.

Background

The incidence of supraventricular arrhythmias following open heart surgery ranges from 20% to 40%, with AF being the most common. Both amiodarone and sotalol have been shown to be effective in reducing postoperative arrhythmias, but no direct comparison of these agents has been conducted.

Methods

A total of 160 patients were randomized, of whom 134 underwent coronary artery bypass graft surgery (CABG) alone, 17 underwent CABG and concomitant aortic valve replacement surgery (AVR), 9 underwent AVR only, and 1 patient's surgery was canceled. Patients with signs or symptoms of congestive heart failure (CHF), ejection fraction ≤30%, estimated creatinine clearance <30 mL/min, or serum creatinine ≥2.5 mg/dL were excluded. Patients were randomized to receive either sotalol 80 mg 2 times per day (n = 76) or intravenous amiodarone 15 mg/kg over 24 hours followed by oral amiodarone 200 mg 3 times per day (n = 83). Study drug was started at the time of surgery and continued for 7 days or until discharge, whichever came first.

Results

AF occurred in 17% of patients randomized to amiodarone and 25% of the patients randomized to sotalol (P = .21). However, the duration of AF was significantly shorter in amiodarone-treated patients (169 ± 224 min) compared to sotalol treated patients (487 ± 505 min; P = .04). In a subgroup analysis, the incidence of AF in patients undergoing AVR or CABG with AVR was significantly less with amiodarone (1/15, 7%) compared to sotalol (9/11, 82%) (P < .001). Blood pressure was lower immediately after surgery with amiodarone but comparable to sotalol at 24 hours. Of the hemodynamic indices measured, only stroke volume was significantly lower in patients randomized to sotalol at 24 hours (P = .035).

Conclusions

Amiodarone and sotalol share similar efficacy and safety in reducing postoperative AF. Hemodynamic effects were similar between both drugs at 24 hours, with the exception that stroke volume was lower in sotalol-treated patients. In patients undergoing more complex surgery, postoperative AF occurred more frequently with sotalol than with amiodarone.     

Walker 256 tumour cells increase substance P immunoreactivity locally and modify the properties of the blood–brain barrier during extravasation and brain invasion

It is not yet known how tumour cells traverse the blood–brain barrier (BBB) to form brain metastases. Substance P (SP) release is a key component of neurogenic inflammation which has been recently shown to increase the permeability of the BBB following CNS insults, making it a possible candidate as a mediator of tumour cell extravasation into the brain. This study investigated the properties of the BBB in the early stages of tumour cell invasion into the brain, and the possible involvement of SP. Male Wistar rats were injected with Walker 256 breast carcinoma cells via the internal carotid artery and euthanised at 1, 3, 6 and 9 days post tumour inoculation. Culture medium-injected animals served as controls at 1 and 9 days. Evidence of tumour cell extravasation across the BBB was first observed at 3 days post-inoculation, which corresponded with significantly increased albumin (p < 0.05) and SP immunoreactivity (p < 0.01) and significantly reduced endothelial barrier antigen labelling of microvessels when compared to culture medium control animals (p < 0.001). By day 9 after tumour cell inoculation, 100 % of animals developed large intracranial neoplasms that had significantly increased albumin in the peri-tumoral area (p < 0.001). The increased SP immunoreactivity and altered BBB properties at 3 days post-inoculation that coincided with early tumour invasion may be indicative of a mechanism for tumour cell extravasation into the brain. Thus, extravasation of tumour cells into the brain to form cerebral metastases may be a SP-mediated process.