The human atrial trabecula: effects of calcium and temperature

The human atrial trabecular preparation is an in vitro model which has been used to evaluate drugs and conditions to which cardiac muscle is exposed perioperatively. During its development, modifications have been made to this preparation. Two important components affecting myocardial muscle contraction are temperature and calcium concentration of the muscle bath medium. Previously, these parameters were determined independently of one another and found to be 34 degrees C and 2.5 mM calcium in a minimal Tyrode's buffer with glucose. This study was undertaken to define the optimal temperature and calcium concentration which would result in the highest yield of muscles that satisfied rigorous criteria for acceptability: developed force (DF) greater than 0.8 g, resting force (RF) less than 0.7 g, cross-sectional area less than or equal to 1.0 mm2). A total of 134 trabeculae were tested using a modified Krebs-Henseleit buffer, enriched with Eagles' medium and containing either 1.25 or 2.5 mM calcium at 34 or 37 degrees C. The trabeculae contracting in 2.5 mM calcium at 37 degrees C resulted in the highest yield of 26% while those maintained at 34 degrees C in either 1.25 or 2.5 mM calcium led to 20 and 15% useful preparations respectively (P = N.S.). Trabeculae contracting at 37 degrees C in 1.25 mM calcium resulted in the poorest yield of 8% (P = 0.002). There is a small (5 to 7%), but significant (P = 0.02), decrease in DF in 1 h when all groups were analyzed together. The exclusion criteria which are applied eliminate variability due to disease and/or treatment, therefore only 20 to 25% are acceptable for study. In summary, with well-defined and stringently applied criteria, the human right atrial trabecular preparation can be a reliable and reproducible model functioning at 37 degrees C and 2.5 mM calcium for a variety of studies.     

A prospective study comparing radiographer- and clinician-based localization for patients with metastatic spinal cord compression (MSCC) to assess the feasibility of a radiographer-led service

Objective:

To investigate whether there was parity between treatment fields localized by radiographers and clinicians, by comparing geographical variations and hence determining the feasibility of a radiographer-led service.

Methods:

23 patients with metastatic spinal cord compression (MSCC) were prospectively sampled. Four radiographers not involved in the original planning performed localization on each patient. The 92 localizations that they determined were compared with the clinician-approved fields. Agreement was defined as ≤0.5 cm between field length, width and three isocentre co-ordinates. To be feasible, agreement was required in a minimum of 97% of the cases. The potential time saved with a radiographer-led approach was also recorded.

Results:

Agreement between clinicians and radiographers was 97.8%. For all field parameters, the average differences were <0.3 cm and were significantly different from the 0.5-cm median (p < 0.0001) that would establish no agreement using Wilcoxon signed-rank test. The average (range) delay awaiting clinician approval was 54 min (4–141 min).

Conclusion:

Strong agreement between radiographer and clinician localizations was established. It was also highlighted that time could be saved in the patient''s pathway by removing the need to wait for clinician approval. We believe this supports a radiographer-led service.

Advances in knowledge:

This article is novel, as it is the first known comparison between clinicians and radiographers in the localization of MSCC radiotherapy. These data show the feasibility of introducing radiographer-led practice and a methodology that could be potentially transferred to investigate the localization parity for other treatment sites.     

Targeting Matrix Metalloproteinase Activity and Expression for the Treatment of Viral Myocarditis

Infectious agents including viruses can infect the heart muscle, resulting in the development of heart inflammation called myocarditis. Chronic myocarditis can lead to dilated cardiomyopathy (DCM). DCM develops from the extensive extracellular matrix (ECM) remodeling caused by myocarditis and may result in heart failure. Epidemiological data for viral myocarditis has long suggested a worse pathology in males, with more recent data demonstrating sex-dependent pathogenesis in DCM as well. Matrix metalloproteinases (MMPs), long known modulators of the extracellular matrix, have important roles in mediating heart inflammation and remodeling during disease and in convalescence. This ability of MMPs to control both the inflammatory response and ECM remodeling during myocarditis makes them potential drug targets. In this review, we analyze the role of MMPs in mediating myocarditis/DCM disease progression, their sex-dependent expression, and their potential as drug targets during viral myocarditis and DCM.     

A systematic review and meta-analysis of biological treatments targeting tumour necrosis factor α for sciatica

Purpose

Systematic review comparing biological agents, targeting tumour necrosis factor α, for sciatica with placebo and alternative interventions.

Methods

We searched 21 electronic databases and bibliographies of included studies. We included randomised controlled trials (RCTs), non-RCTs and controlled observational studies of adults who had sciatica treated by biological agents compared with placebo or alternative interventions.

Results

We pooled the results of six studies (five RCTs and one non-RCT) in meta-analyses. Compared with placebo biological agents had: better global effects in the short-term odds ratio (OR) 2.0 (95 % CI 0.7–6.0), medium-term OR 2.7 (95 % CI 1.0–7.1) and long-term OR 2.3 [95 % CI 0.5 to 9.7); improved leg pain intensity in the short-term weighted mean difference (WMD) −13.6 (95 % CI −26.8 to −0.4), medium-term WMD −7.0 (95 % CI −15.4 to 1.5), but not long-term WMD 0.2 (95 % CI −20.3 to 20.8); improved Oswestry Disability Index (ODI) in the short-term WMD −5.2 (95 % CI −14.1 to 3.7), medium-term WMD −8.2 (95 % CI −14.4 to −2.0), and long-term WMD −5.0 (95 % CI −11.8 to 1.8). There was heterogeneity in the leg pain intensity and ODI results and improvements were no longer statistically significant when studies were restricted to RCTs. There was a reduction in the need for discectomy, which was not statistically significant, and no difference in the number of adverse effects.

Conclusions

There was insufficient evidence to recommend these agents when treating sciatica, but sufficient evidence to suggest that larger RCTs are needed.

Electronic supplementary material

The online version of this article (doi:10.1007/s00586-013-2739-z) contains supplementary material, which is available to authorized users.     

Soluble Fas ligand activates the sphingomyelin pathway and induces apoptosis in luteal steroidogenic cells independently of stress-activated p38(MAPK)

Fas ligand (FasL) is implicated as a mediator of luteolysis. However, a gap exists in our understanding of the Fas-mediated signaling mechanisms that are involved in either the loss of progesterone production or the structural regression of the corpus luteum. In the present study we investigated the acute and chronic effects of FasL with respect to activation of cytokine/stress-induced signaling pathways and apoptosis in bovine steroidogenic cells. More specifically, we investigated soluble FasL (sFasL)-activated production of ceramide, a second messenger of the sphingomyelin pathway, and activation of p38(MAPK), a member of the MAPK family. sFasL activated the sphingomyelin pathway, as evidenced by a 2-fold increase (P < 0.05) in the production of ceramide. Pretreatment with imipramine (50 micro M), an inhibitor of acid sphingomyelinase activity, attenuated (75%; P < 0.05) sFasL-induced ceramide production, suggesting that the increase in ceramide was partially the result of acid sphingomyelinase-mediated hydrolysis of sphingomyelin. Treatment of luteal cells with sFasL or a cell-permeable ceramide analog (C8) for 24-48 h resulted in a significant increase (P < 0.05) in apoptosis. Western blot analysis revealed that sFasL had little effect on the activation of p38(MAPK) in primary bovine luteal steroidogenic cells. Furthermore, pretreatment with the p38(MAPK) inhibitor SB203580 failed (P > 0.05) to inhibit sFasL- or C8-induced death. Although sFasL did not alter basal progesterone levels detected in the culture medium, C8 caused a significant increase (P < 0.05) in progesterone concentrations within the medium. Collectively, these data suggest that the role of FasL in luteolysis may be to activate the stress-induced sphingomyelin pathway that, in turn, serves as a mediator of apoptosis.     

The Robustness of the Early and Late Start Typology of Criminal Behaviour in Major Mental Disorder: A Conceptual Replication

The purpose of this study was to examine whether the early and late start typology of criminal behaviour in major mental disorder can be generalized to different populations than evaluated to date and is replicable in two different countries. A Dutch forensic sample (Sample 1) consisted of 260 reports to the court with early start offenders (n = 62) and late start offenders (n = 198). A Canadian civil psychiatric sample (Sample 2) consisted of file information collected from 78 involuntarily hospitalized civil psychiatric patients with an early start group (n = 38) and a late start group (n = 40). In both samples, early and late starters were compared on different domains. Results showed that in general, early starters have a higher risk of having problems in different domains. There were also differences in the early and late start typology between the Dutch and Canadian samples. Our results partially support the early and late starter typology within two different samples. This study showed that early starters typically have a higher risk of problems in different domains. This highlights the importance of different risk management and treatment strategies for both the early start and the late start group.     

Hepatic decompensation in patients with cirrhosis during infection with influenza A

BACKGROUND: Patients with chronic liver disease can develop hepatic decompensation during systemic infections. Although gram-negative and gram-positive bacteria are well recognized as causes of decompensation, the effect of influenza virus infection on patients with chronic liver disease is poorly documented. METHODS: Retrospective analysis of patients with positive viral cultures who were seen at a liver transplantation clinic in a tertiary care referral center during the 1997-1998 influenza A (H3N2) epidemic in San Diego, Calif. RESULTS: Three patients with end-stage liver disease (1 with Wilson disease and 2 with alcoholic liver disease) developed hepatic decompensation and required hospitalization during infection with influenza A. Two patients had biochemical and clinical evidence of hepatic decompensation, including ascites, hepatic encephalopathy, and peripheral edema, and the third had acute hepatocellular damage, with elevated levels of aminotransferases. Viral hepatitis serologic test results, acetaminophen levels, drug and alcohol screening findings, and bacterial and fungal cultures were negative in all 3 patients. Hepatic decompensation resolved without the need for transplantation in the 2 patients with liver failure, and all patients recovered to their baseline liver function levels within 1 month of onset of acute illness. CONCLUSIONS: Influenza A infection can cause hepatic decompensation and hospitalization in patients having cirrhosis or who are awaiting liver transplantation. Effective prevention with vaccination and early recognition and treatment of influenza are strongly recommended in these individuals.