Effects of passive cardiac containment on left ventricular structure and function: verification by volume and flow measurements.

BACKGROUND: The cardiac support device (CSD, Acorn) is a compliant, textile-mesh graft placed around the ventricles to prevent further dilatation and to improve function in congestive heart failure. The aim of this study was to verify post-operative changes in left ventricular volumes, ejection fraction, blood flow, and myocardial mass. METHODS: Fourteen patients underwent contrast-enhanced, electrocardiography-triggered electron-beam computerized tomography before and 6 to 9 months after CSD implantation. We measured volume and flow using the slice-summation method and the indicator-dilution technique. RESULTS: We found significant changes for the following parameters: end-diastolic volume decreased from 382.9 +/- 140.2 ml to 311.3 +/- 138.7 ml, end-systolic volume from 310.4 +/- 132.4 ml to 237.4 +/- 133.8 ml, end-diastolic diameter from 75.3 +/- 7.8 mm to 70.7 +/- 11.6 mm, end-systolic diameter from 65.8 +/- 7.8 mm to 60.0 +/- 14.0 mm, and myocardial mass from 298.6 +/- 79.6 g to 263.1 +/- 76.8 g. Ejection fraction increased from 20.3% +/- 6.4% to 27.8% +/- 13.1%. We found no significant differences for stroke volume (from 72.5 +/- 24.6 ml to 73.8 +/- 23.6 ml), heart rate (from 80.5 +/- 11.0 beats per minute to 76.5 +/- 6.8 beats per minute), and total cardiac output (from 5.8 +/- 1.9 liter/min to 5.6 +/- 1.8 liter/min). Mitral regurgitation fraction decreased from 30.5% +/- 15.5% to 15.6% +/- 12.8%, increasing antegrade cardiac output from 3.8 +/- 0.9 liter/min to 4.7+/-1.5 liter/min. For most parameters, pre- and post-operative values in these patients differed significantly from those in an age- and gender-matched control group. In each patient, we observed a small hyperdense stripe along the pericardium after surgery, but we observed no local complications. CONCLUSION: Three-dimensional structural and functional data obtained by computerized tomography volume and flow measurements confirm the safety and efficacy of CSD implantation.     

Basic extraction studies of benzylpenicillin and its determination by liquid chromatography with pre-column derivatisation

In order to develop a sensitive and precise chemical bioanalysis of benzylpenicillin in biological fluids, basic studies on benzylpenicillin are presented. These studies include pH dependent stability, extraction in aqueous ethylacetate systems in different pH and buffer compositions. A pre-column derivatisation LC method for the detection of benzylpenicillin also is described. The derivatisation of the sample is performed by the beta-lactam ring specific formation of the mercuric(II)mercaptide of the penicillenic acid in the presence of imidazole. The UV spectral properties of the derivative are utilised for detection. The chromatographic conditions are optimised with reference to the pH, the methanol, the imidazole and the mercury(II)chloride content of the mobile phase as well as the column temperature.     

Incidence and morphology of spontaneous thyroid tumours in different strains of rats

The incidence and morphology of thyroid neoplasms in different strains and stocks of rats are reported. The frequency of thyroid tumours varied to a great extent between different strains of rats. Low incidences were observed in DA/Han (0.85 per cent) and BDII/Han rats (1.25 per cent), while somewhat higher incidences occurred in Han:WIST rats (7.3 per cent). The highest number of thyroid tumour-bearing rats was found in the Han:SPRD stock (55.5 per cent). Thyroid neoplasms were classified histologically as polymorphofollicular adenomas, papillary adenomas, cystadenomas, polymorphofollicular carcinomas, papillary carcinomas, C-cell adenomas and C-cell carcinomas (medullary carcinomas). C-cell neoplasms were predominant in Han:SPRD rats (93.0 per cent), while the majority of tumour-bearing Han:WIST rats (61.4 per cent) had follicular tumours.     

Long-term stable fibrin gels for cartilage engineering

It is essential that hydrogel scaffold systems maintain long-term shape stability and mechanical integrity for applications in cartilage tissue engineering. Within this study, we aimed at the improvement of a commercially available fibrin gel in order to develop a long-term stable fibrin gel and, subsequently, investigated the suitability of the optimized gel for in vitro cartilage engineering. Only fibrin gels with a final fibrinogen concentration of 25mg/ml or higher, a Ca(2+) concentration of 20mm and a pH between 6.8 and 9 were transparent and stable for three weeks, the duration of the experiment. In contrast, when preparing fibrin gels with concentrations out of these ranges, turbid gels were obtained that shrank and completely dissolved within a few weeks. In rheological characterization experiments, the optimized gels showed a broad linear viscoelastic region and withstood mechanical loadings of up to 10,000 Pa. Bovine chondrocytes suspended in the optimized fibrin gels proliferated well and produced the extracellular matrix (ECM) components glycosaminoglycans and collagen type II. When initially seeding 3 million cells or more per construct (5mm diameter, 2mm thick), after 5 weeks of culture, a coherent cartilaginous ECM was obtained that was homogenously distributed throughout the whole construct. The developed fibrin gels are suggested also for other tissue engineering applications in which long-term stable hydrogels appear desirable.     

Phenotype of NK Cells Determined on the Basis of Selected Immunological Parameters in Children Treated due to Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is the most frequent pediatric malignancy. The chemotherapy for ALL is associated with a profound secondary immune deficiency.We evaluated the number and phenotype of natural killer (NK) cells at diagnosis, after the intensive chemotherapy and following the completion of the entire treatment for patients with ALL. The fraction, absolute number, and percentage of NK cells expressing interferon-γ were determined in full blood samples. The fraction of NK cells expressing CD158a, CD158b, perforin, A, B, and K granzymes was examined in isolated NK cells.We have shown that patients assessed at ALL diagnosis showed significantly lower values of the fraction of NK cells and percentage of NK cells with the granzyme A expression. Additionally, the absolute number of NK cells, the expression of CD158a, CD158b, perforin, and granzyme A were significantly lower in patients who completed intensive chemotherapy. Also, there was a significantly higher fraction of NK cells expressing granzyme K in patients who completed the therapy.Abnormalities of NK cells were found at all stages of the treatment; however, the most pronounced changes were found at the end of intensive chemotherapy.     

Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal antibody therapy for RAS wild-type metastatic colorectal cancer

Background:

Metastatic colorectal cancer (mCRC) that harbours a BRAF V600E mutation (BRAF MT) is associated with poorer outcomes. However, whether this mutation is predictive of treatment benefit from anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) is uncertain.

Methods:

We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) published up to July 2014 that evaluated the effect of BRAF MT on the treatment benefit from anti-EGFR mAbs for mCRC.

Results:

Seven RCTs met the inclusion criteria for assessment of overall survival (OS), whereas eight RCTs met the inclusion criteria for assessment of progression-free survival (PFS). For RAS WT/BRAF MT tumours, the hazard ratio for OS benefit with anti-EGFR mAbs was 0.97 (95% CI; 0.67–1.41), whereas the hazard ratio was 0.81 (95% CI; 0.70–0.95) for RAS WT/BRAF WT tumours. However, the test of interaction (P=0.43) was not statistically significant, highlighting that the observed differences in the effect of anti-EGFR mAbs on OS according to the BRAF mutation status may be due to chance alone. Regarding PFS benefit with anti-EGFR mAbs, the hazard ratio was 0.86 (95% CI; 0.61–1.21) for RAS WT/BRAF MT tumours as compared with 0.62 (95% CI; 0.50–0.77) for RAS WT/BRAF WT tumours (test of interaction, P=0.07).

Interpretation:

This meta-analysis demonstrates that there is insufficient evidence to definitively state that RAS WT/BRAF MT individuals attain a different treatment benefit from anti-EGFR mAbs for mCRC compared with RAS WT/BRAF WT individuals. As such, there are insufficient data to justify the exclusion of anti-EGFR mAb therapy for patients with RAS WT/BRAF MT mCRC.     

Significance of viral hepatitis in a dialysis center for patients and health personnel--a 5-year review

As a nosocomial infection the virus hepatitis is now as ever of importance in dialysis centres. In a 5-year study (1980-1985) in the dialysis centre of the County Hospital St. Georg Leipzig we found an annual incidence of 14 to 20% in patients and in 25 out of 26 members of the staff signs of an overcome infection could be proved. In these cases above all younger persons with an average age of 31 years were affected about 1.5 years after the beginning of work. For patients the entry into the transplant recipient register retarded by on an average 9.4 months, for patients already registered a transient reincorporation of 12.4 months was the result. Despite the active inoculation against the virus hepatitis B on account of the further existing endangering by the NANB hepatitis and possible inoculation eruptions in the immune-disturbed dialysis patients the observation of a strong hygiene regimen is necessary.