ECG changes in patients with acute ethanol intoxication

Objectives. To assess how ethanol in potential lethal serum concentrations affects features of the ECG that may be associated with cardiac arrhythmias. Design. We included 84 patients, who were hospitalised with assumed acute ethanol intoxication. In the emergency room resting ECG was recorded and blood was collected for serum osmolality measurement used as a proxy for ethanol level. Thirty-two also had ECG recorded at discharge. Twenty-seven hospitalised patients without known alcohol ingestion served as controls. ECG segment durations were compared with controls and related to intoxication level. Results. In subjects with moderately elevated to high serum osmolality, the P wave and QTc intervals were prolonged compared with sober subjects. P wave, PR, QRS and QTc intervals were longer when the subjects had high blood ethanol levels (at admission) than at discharge (p-values: 0.0001, 0.0002, 0.010 and < 0.0001 for P wave, PR, QRS and QTc intervals. n = 32). Conclusions. Ethanol at high to very high blood concentration causes several changes in the ECG that might be associated with increased risk of arrhythmias.     

Comparison of the centrifugal and roller pump in elective coronary artery bypass surgery—a prospective,randomized study with special emphasis upon platelet activation

Objective—Evaluation of the centrifugal pump vs roller pump concerning effects upon platelet function, hemolysis and clinical outcome in elective coronary artery bypass surgery.

Design—Thirty‐four patients were randomized to centrifugal or roller pump. Platelet activation was studied by flow cytometry before, during and up to 3 days after bypass.

Results—Duration of bypass, ischemic period, peripheral anastomoses, hospital stay and mortality did not differ. In roller pump patients, platelet aggregates increased by 250% between end of bypass and 3?h postoperatively (p?<?0.001). A secondary, fivefold increase in number of platelet aggregates was found on the 3rd postoperative day (p?<?0.001). In the centrifugal pump group, these changes were not significant. Hemolysis increased (20%) at end of bypass and 3?h postoperatively (p?<?0.005), and decreased to preoperative levels the next day without group difference.

Conclusion—Platelet aggregation was significantly increased in roller compared with centrifugal pump patients, indicating higher susceptibility to postoperative thrombotic complications with the roller pump. Otherwise, there was no clinical evidence for superiority of the centrifugal pump.     

Expression of transforming growth factor-beta receptor type 1 and type 2 in human sporadic vestibular Schwannoma

Expression of the transforming growth factor-beta (TGF-beta) protein family in the peripheral nervous system is well established, but the role of their cognate receptors TGF-beta receptor type 1 (R1) and type 2 (R2) has been less well studied. TGF-beta plays an essential role in Schwann cell proliferation and differentiation, and is involved in neurotrophic effects of several neurotrophic substances. TGF-beta is also expressed in benign peripheral nervous system tumors such as vestibular schwannomas. In the present study, we aimed to detect TGF-beta R1 and R2 in a total of 40 sporadic vestibular schwannomas using immunohistochemistry, and correlated the findings to essential clinicopathologic data. TGF-beta, TGF-beta R1, and TGF-beta R2 mRNA was further analyzed by RT-PCR in six vestibular schwannomas. TGF-beta R1 immunoexpression was found in about 95% of the tumors. TGF-beta R1 was equally present in Antoni A and Antoni B areas of the tumors. TGF-beta R2 was found immunohistochemically in 77%. In addition, all tumors showed strong expression of TGF-beta. No correlation between TGF-beta R1 or R2 expression and clinicopathologic parameters such as age, sex, clinical symptoms, growth pattern, and proliferation acitivity as measured by Ki-67 (MIB-1) staining was found. Moreover, all schwannomas studied contained TGF-beta, TGF-beta R1, and TGF-beta R2 mRNA. Therefore, the TGF-beta/TGF-beta R1 and -R2 system is present in human schwannomas, but its biologic role for tumor development and growth remains unclear.     

Flexions- und Extensionsosteotomien der proximalen Tibia

Background

Isolated deviations in flexion and extension of the leg axis are rare. These deviations can be corrected if necessary by osteotomy and the range of motion (ROM) of the knee joint can be optimized. In addition to correction in the frontal plane, the tibial slope (i.e. inclination of the surface of the tibial joint) can also be influenced by osteotomy and therefore osteotomy can also be utilized to optimize the biomechanical stability of the knee joint.

Method

Careful planning taking all three spatial planes and torsion into consideration is the foundation of a successful operation. A controlled surgical technique based on careful planning and some basic principles allows the alteration of the three dimensional alignment of the tibia.     

Heart transplantation for end-stage heart failure caused by iron overload

Few reports exist concerning heart transplantation in recipients with end-stage myocardiopathy-associated heart failure caused by iron overload occurring with β-thalassaemia, Diamond-Blackfan syndrome or haemochromatosis. Seven potential transplant candidates (six male, one female, mean age 26 years) with such heart failure, following desferrioxamine application subcutaneously over a number of years, and intravenously during their hospitalization before transplantation, were retrospectively analysed. Five were New York Heart Association (NYHA) class IV, three experienced one or more resuscitations immediately before transplantation could be performed. Continuous, high-volume, veno-venous haemofiltration was necessary in two patients. One of these two candidates additionally had to be bridged, first with a right ventricular, then with a biventricular assist device. Five of the seven patients survived, two with haemochromatosis, one with β-thalassaemia major and one with Diamond-Blackfan syndrome following transplantation. One non-transplanted candidate with β-thalassaemia major has been recompensated for 5 years. Survival was 14–74 months. Our results demonstrate the feasibility and indication of transplantation in patients with such heart failure and the satisfying outcome of immunosuppression is described.     

GCK-MODY diabetes as a protein misfolding disease: The mutation R275C promotes protein misfolding,self-association and cellular degradation

GCK-MODY, dominantly inherited mild hyperglycemia, is associated with more than 600 mutations in the glucokinase gene. Different molecular mechanisms have been shown to explain GCK-MODY. Here, we report a Pakistani family harboring the glucokinase mutation c.823C > T (p.R275C). The recombinant and in cellulo expressed mutant pancreatic enzyme revealed slightly increased enzyme activity (k_cat) and normal affinity for α-D-glucose, and resistance to limited proteolysis by trypsin comparable with wild-type. When stably expressed in HEK293 cells and MIN6 β-cells (at different levels), the mutant protein appeared misfolded and unstable with a propensity to form dimers and aggregates. Its degradation rate was increased, involving the lysosomal and proteasomal quality control systems. On mutation, a hydrogen bond between the R275 side-chain and the carbonyl oxygen of D267 is broken, destabilizing the F260-L271 loop structure and the protein. This promotes the formation of dimers/aggregates and suggests that an increased cellular degradation is the molecular mechanism by which R275C causes GCK-MODY.