Blood stream infection is associated with cerebrovascular accident in patients with left ventricular assist device: a systematic review and meta-analysis

Cerebrovascular accident (CVA) is one of the major complications and a leading cause of death in patients with a left ventricular assist device (LVAD). Multiple studies of have shown that patients with blood stream infection (BSI) are more likely to develop CVA compared to patients without BSI. However, there is no meta-analysis to confirm this association. Studies were systematically acquired from MEDLINE and EMBASE electronic databases. Included studies assessed patients with heart failure requiring LVAD and reported the number of patients who had BSI post LVAD, incidence of ischemic CVA, hemorrhagic CVA, or any CVA. Pooled effect size was calculated with a random-effect model, weighted for the inverse of variance. Heterogeneity was assessed with I². Six studies were analyzed. Participants with LVAD who developed BSI were more likely to have a CVA compared to participants without BSI (RR 3.43, 95% CI 2.49–4.72, I²?=?0). In four studies, there was an association between BSI and increased incidence of hemorrhagic CVA post LVAD (RR 5.28, 95% CI 2.65–10.53) with minimal heterogeneity (I²?=?30%). In three studies, participants with BSI were more likely to develop ischemic CVA (RR 2.18, 95% CI 1.23–3.84) compared to patients without BSI. This meta-analysis suggested that there maybe an association between blood stream infection and cerebrovascular accident in patients with LVAD.     

New mutant and congenic mouse stocks expressing the murine leukemia virus-associated thymocyte surface antigen G(IX)

For several reasons the G(IX) antigen (1) has a prominent place in current work on murine leukemia virus (MuLV): In the prototype G(IX+) mouse strain 129, the G(IX) trait is mendelian, and is expressed selectively (though not exclusively) on thymocytes. Thus, expression of this cell surface component is under the control of cellular genes and is subject to the controls governing the differentiation of T lymphocytes (2). Although the 129 mouse produces no demonstrable leukemia virus such as that found in the AKR strain, it was soon realized that G(IX) antigen must in some way be related to MuLV, because productive infection with MuLV is frequently associated with appearance of G(IX) antigen on cells that are genotypically G(IX-), most notably on MuLV-infected rat cells, or cells that belong to other differentiation pathways (1). The basis of this connection between G(IX) and MuLV has recently become clear from the demonstration that G(IX) is one of MuLV envelope. Therefore, our working hypothesis is that the presence of G(IX) is one of the antigens present on gp69/71 (3,4), the major glycoprotein component of the MuLV envelope. Therefore, our working hypothesis is that the presence of G(IX) antigen always denotes the presence of gp69/71 (though not all variants of gp69/71 need necessarily carry G(IX)). Study of the circumstances under which G(IX) is expressed on the cell surface is thus potentially a powerful approach to understanding how the expression of C-type viral genomes is controlled. Such studies are greatly facilitated by the availability of mutant and congenic strains of inbred mice which differ from the nonmutant or partner strains only with respect to one or another manifestation of the viral genome. It is for this reason that we record here (Table I) some details of two G(IX) mutant and two G(IX) congenic stocks derived in our colonies at Memorial Sloan-Kettering Cancer Center (MSKCC). In addition, to these four strains, Table I includes data for the three relevant partner strains, and for strain AKR, for comparison. These eight strains all differ from one another with respect to one or more MuLV-related traits.     

Alpha lipoic acid attenuates inflammatory response during extracorporeal circulation

Aim

Extracorporeal circulation (ECC) of blood during cardiopulmonary surgery has been shown to stimulate various pro-inflammatory molecules such as cytokines and chemokines. The biochemical oxidation/reduction pathways of a-lipoic acid suggest that it may have antioxidant properties.

Methods

In this study we aimed to evaluate only patients with coronary heart disease and those planned for coronary artery bypass graft operation. Blood samples were obtained from the patients before the operation (P1) and one (P2), four (P3), 24 (P4) and 48 hours (P5) after administration of a-lipoic acid (LA). The patients were divided into two groups, control and LA treatment group. Levels of interleukin-6 (IL-6) and -8 (IL-8), complement 3 (C3) and 4 (C4), anti-streptolysin (ASO), C-reactive protein (CRP) and haptoglobin were assessed in the blood samples.

Results

Cytokine IL-6 and IL-8 levels were significantly higher after surgery. Compared with the control groups, LA significantly decreased IL-6 and IL-8 levels in a time-dependent manner. CRP levels did not show significant variation in the first three time periods. CRP levels were higher after surgery, especially in the later periods. These results demonstrate that CRP formation depends on cytokine release. C3 and C4 levels were significantly higher after surgery than in the pre-operative period. LA treatment decreased C3 and C4 levels. Therefore, LA administration may be useful for the treatment of diseases and processes where excessive cytokine release could cause oxidative damage.

Conclusions

Our findings suggest a possible benefit of using LA during cardiac surgery to reduce cytokine levels.     

The occurrence of Helicobacter pylori in hydatid liver disease

Objective

To detect the prevalence of Helicobacter pylori (H. pylori) in hydatid liver disease.

Methods

A total of 58 patients with hydatid liver disease attending AL-Sadder Teaching Hospital in Al-Najaf and Al-Basrah governorate from February to August, 2008 were included in the study and served as group A. One hundred and twenty 1st degree relative patients (group B) and 20 normal persons including 10 male and 10 female (group C) as control were detected for the presence of H. pylori infection in general population. Chest X-ray was done for the above groups to exclude lung hydrated cyst. The patients were screened by ultrasound to obtain intra abdominal hydrated cyst and enzyme-linked immuno sorbent assay (ELISA) test was utilized to detect the H. pylori infection.

Results

Fifty eight patients from group A with hydatid liver disease, 30 male (51.7%) and 28 female (48.3%) were screened for the presence of H. pylori infection by using ELISA test. We found that 28 patients from group A had positive ELISA test including 19 male (32.8%) and 9 female (15.5%) (P<0.01). However, there were no positive results of H. pylori infection in group B and C by chest X-ray, ultrasound and ELISA test.

Conclusions

It can be concluded that there is a strong relationship between hydatid liver disease and presence of H. pylori.     

Sertraline inhibits the transport of PAT1 substrates in vivo and in vitro

Background and Purpose

Intestinal nutrient transporters may mediate the uptake of drugs. The aim of this study was to investigate whether sertraline interacts with the intestinal proton-coupled amino acid transporter 1 PAT1 (SLC36A1).

Experimental Approach

In vitro investigations of interactions between sertraline and human (h)PAT1, hSGLT1 (sodium-glucose linked transporter 1) and hPepT1 (proton-coupled di-/tri-peptide transporter 1) were conducted in Caco-2 cells using radiolabelled substrates. In vivo pharmacokinetic investigations were conducted in male Sprague–Dawley rats using gaboxadol (10 mg·kg⁻¹, p.o.) as a PAT1 substrate and sertraline (0–30.6 mg·kg⁻¹). Gaboxadol was quantified by hydrophilic interaction chromatography followed by MS/MS detection.

Key Results

Sertraline inhibited hPAT1-mediated L-[³H]-Pro uptake in Caco-2 cells. This interaction between sertraline and PAT1 appeared to be non-competitive. The uptake of the hSGLT1 substrate [¹⁴C]-α–methyl-D-glycopyranoside and the hPepT1 substrate [¹⁴C]-Gly-Sar in Caco-2 cells was also decreased in the presence of 0.3 mM sertraline. In rats, the administration of sertraline (0.1–10 mM, corresponding to 0.3–30.6 mg·kg⁻¹, p.o.) significantly reduced the maximal gaboxadol plasma concentration and AUC after its administration p.o.

Conclusions and Implications

Sertraline is an apparent non-competitive inhibitor of hPAT1-mediated transport in vitro. This inhibitory effect of sertraline is not specific to hPAT1 as substrate transport via hPepT1 and hSGLT1 was also reduced in the presence of sertraline. In vivo, sertraline reduced the amount of gaboxadol absorbed, suggesting that the inhibitory effect of sertraline on PAT1 occurs both in vitro and in vivo. Hence, sertraline could alter the bioavailability of drugs absorbed via PAT1.     

Physical exertion and working efficiency of reforestation workers

Background

The purpose of this study was to quantify the physical exertion during tree planting work and to examine the relationships between exertion, task efficiency, and productivity.

Methods

Heart rate (HR) was monitored on 34 tree planters while they worked. HR data was collected for a complete working day on 19 subjects and for shorter periods of time on 15 subjects. Video of work tasks was recorded on 22 subjects (video was recorded on 7 of the subjects for whom HR was monitored through a full working day) and analyzed for working pace and proportion of time spent on each task.

Results

HR during a full day (9.0 ± 1.2 hours) of tree planting work was 115.2 ± 8.8 beats.min^-1, and working HR was 128.2 ± 15.6 beats.min^-1 for 82.5 ± 6.8% of the work day. Mean work pace was 452 ± 174 trees.h^-1, and the proportion of time spent planting each tree was 53 ± 8% of the working time. Significant (P < 0.05) positive correlations were found between work pace and experience level, and between work pace and working HR, and a significant (P < 0.05) negative correlation was found between experience level and HR for a given work pace. No significant relationships were found between experience level or work pace and the proportion of time spent planting each tree.

Conclusions

Tree planters work at approximately 65% of age-predicted HR_max, and maintain HR at approximately 59% of HR_max throughout the entire working day. Productivity in these workers appears to be related to effort rather than to experience or task efficiency per se.     

Therapeutic approach to hormone-refractory prostate cancer

Over 60 years ago, Huggins and Hodges discovered androgen deprivation as an effective first-line therapy for metastatic prostate cancer. This leads to significant cancer control but in almost all men prostate cancer ultimately progresses to a hormone-refractory (HRPC) state resulting in significant morbidity and eventual death. In 2004, two landmark studies using docetaxel based chemotherapy demonstrated, for the first time, a survival advantage in HRPC. This has set a new standard of care for this disease. In addition, treatment with the bisphosphonate zoledronic acid has been shown to significantly reduce bone complications in metastatic HRPC. Building on these advances, several new docetaxel/zoledronic acid based combinations as well as new targeted therapies are under development. Introducing these effective therapies earlier in high risk patients is also under investigation to further improve outcomes.