ABSTRACT:Sorafenib (Nexavar) is a novel oral Raf kinase and vascular endothelial growth factor receptor inhibitor. Most anticancer drugs are substrates for ATP-binding cassette efflux pumps especially for P-glycoprotein (P-gp). To evaluate the influence of P-gp on the pharmacokinetics of sorafenib substrate properties for this transporter were investigated. Therefore, permeability of sorafenib across Caco-2 and P-gp-overexpressing cells was determined. To determine the in vivo relevance of these in vitro findings, pharmacokinetics of sorafenib in mdr1a/1b(؊/؊) and wild-type (WT) mice was studied. Sorafenib is highly permeable and exhibits a slight efflux across Caco-2 cells. In P-gp-overexpressing cells, a small concentration-dependent efflux was observed, which was completely blocked by the addition of ivermectin. In mdr1a/1b(؊/؊) and WT mice, unchanged compound represented by far the majority of radioactivity in plasma. After intravenous and oral administration, brain/plasma concentration ratios in mdr1a/1b(؊/؊) mice were 1.3-to 1.5-fold higher than those in WT mice. However, after intravenous or oral administration, plasma concentrations were similar in both mouse strains. In conclusion, sorafenib is highly permeable and a weak P-gp substrate in vitro. These findings were confirmed by the small factor of 1.3 to 1.5 observed for the brain/plasma ratios in mdr1a/1b(؊/؊) versus WT mice in vivo. Based on these in vitro and in vivo results, it is unlikely that P-gp has a major effect on the plasma concentrations of sorafenib in humans. Because of the high permeability and low P-gp-mediated transport, sorafenib might be able to cross the blood-brain barrier and target tumors within the brain.
Many children and adolescents with mental health problems do not receive the treatment they need. Unmet need raises questions about specific barriers that may prevent service use, and/or the characteristics of children and families who are less likely to receive care. Brief interventions or single-session psychotherapy delivered in a highly accessible manner are methods of addressing the problems associated with waitlists and limited access to care. In the current study the authors offer an exploratory evaluation of the West End Walk-In Counseling Centre for children and youth with psychosocial problems. Children 4 to 18 years of age who accessed the Walk-In Counseling Centre and a comparison group of clients who accessed usual care were assessed at intake, post-treatment, and 3-month follow-up on demographic characteristics, behavioral/emotional adjustment and functioning, client satisfaction, and service use. Children in the walk-in group had more severe behavioral/emotional adjustment and functioning than usual care clients at baseline. At post-treatment, walk-in clients had lower scores on Total Mental Health Problems and Internalizing Behaviors, and exhibited fewer problems across all scales at follow-up. Walk-in clients found the wait time for service more reasonable and at follow-up, felt the service addressed concerns and had higher regard for counselor availability and cultural sensitivity of the service than usual care clients. Service utilization, assessed at post-treatment and 3-month follow-up, showed that both groups were more likely to access mental health and education services rather than health or child welfare services, and were more likely to have used services in the 12 months prior to service than the 3 months following service completion. Walk-in clients had steeper rates of improvement compared to usual care clients despite equivalence in psychosocial functioning at baseline. The walk-in model may be an effective alternative to usual care, particularly for those clients only willing to wait up to 2 weeks for service.
Between August 1980 and August 1981 a prospective randomised study was conducted at the Krankenhaus Nordwest , Dept. of OBGYN , Frankfurt, to investigate the efficacy of a short term prophylaxis using mezlocillin and oxacillin ( Optocillin ) in reducing infections after Caesarean section (6 gs Optocillin after clamping the umbilical cord and after 8 and 16 hours, respectively). Both the study group (sg) and the control group (cg) consisted of 50 patients each. Both groups were statistically homogeneous . Infections were significantly reduced by the prophylaxis: sg 26%/cg 64% - p less than 0,001, febrile morbidity: sg 10%/cg 38% - p less than 0,001, endometritis: sg 6%/cg 20% - p less than 0,08, UTI: sg 18%/cg 36% - p less than 0,05, wound infections: sg 2%/cg 18% - p less than 0,02. Severe infections, however, were seen in neither group. The duration of infections was shorter in the sg. The various postoperative infections were associated with different risk factors (rf) - endometritis: green amniotic fluid, operating time greater than 75 min; cervical dilatation less than 2 cm, UTI: PROM (greater than 6 hs), operating time less than 75 min, internal monitoring, cervical dilatation greater than 2 cm, wound infections: green amniotic fluid, internal monitoring, frequent vaginal examinations (greater than 6), cervical dilatation greater than 2 cm and operating time greater than 75 min. The prophylaxis was especially effective in the presence of the following rfs: green amniotic fluid, internal monitoring, frequent vaginal examinations (6), operating time greater than 75 min and when associated with combined rfs. The reduction of wound infections following the prophylaxis can be ascribed to the elimination of organisms (Staph. spec., enterococci,) at the site of operation.(ABSTRACT TRUNCATED AT 250 WORDS)
All tests for hypermobility and 23 tests for the stabilisation system are suitable for further evaluation. The broad range in test reliability might be explained by the differences in examiner skills demanded by each test. Therefore, dependent on their validity, some tests will be useful in specialized centres while others might be used in primary care.
In a primigravida with a fundal/anterior wall placenta, a successful cephalic version was noted at 39 weeks after repeated moxibustion of the point Zhiyin (bl 67). Since routine foetal heart rate monitoring showed a sinusoidal pattern with severe decelerations, immediate Caesarean section was performed. Foetomaternal macrotransfusion of about 300 ml of blood was found. In view of this complication, possible risks of the method are discussed. Moxibustion does not seem to be suitable as self-therapy without close medical follow-up.
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