The RECIST criteria compared to conventional response evaluation after peptide receptor radionuclide therapy in patients with neuroendocrine neoplasms

Annals of Nuclear Medicine - The Response Evaluation Criteria In Solid Tumors (RECIST) is the most used radiological method for evaluating response after peptide receptor radionuclide therapy...     

Curriculum factors influencing knowledge of communication skills among medical students

Background  

Communication training builds on the assumption that understanding of the concepts related to professional communication facilitates the training. We know little about whether students' knowledge of clinical communication skills is affected by their attendance of communication training courses, or to what degree other elements of the clinical training or curriculum design also play a role. The aim of this study was to determine which elements of the curriculum influence acquisition of knowledge regarding clinical communication skills by medical students.     

Moment-to-moment dynamics of ADHD behaviour in South African children

Background  

The behaviour of children with Attention-Deficit/Hyperactivity Disorder is characterized by low predictability of responding. Low behavioural predictability is one way of operationalizing intra-individual ADHD-related variability. ADHD-related variability may be caused by inefficient behavioural selection mechanisms linked to reinforcement and extinction, as suggested by the recently published dynamic developmental theory (DDT) of ADHD. DDT argues that ADHD is a basic neurobehavioural disorder, caused by dysfunctioning dopamine systems. For establishing ADHD as a neurobehavioural disorder, findings from studies conducted in Western countries should be replicated in other cultural populations. The present study replicated the study conducted in Norway, with children from the Limpopo province in the Republic of South Africa.     

Linomide,a novel immunomodulator that prevents death in four models of septic shock

Intravenous injections of 50 μ.g Staphylococcus aureus enterotoxin B (SEB) or bacterial lipopolysaccharide (LPS) are lethal, provided that mice are simultaneously sensitized with either N-galactosamine (GalN) or the anti-glucocorticoid RU-38486. Similar to the synthetic glucocorticoid (GC) receptor agonist dexamethasone, pharmacological doses of the immunomodulator linomide (quinoline-3-carboxamide) prevent death in all four models of lethal septic shock (LPS + GalN, LPS + RU-38486, SEB + GalN, and SEB + RU-38486) and inhibit the secretion of tumor necrosis factor, one of the major intermediate effector molecules of SEB and LPS toxicity. In this system, cyclosporine A (CsA), although effective in suppressing SEB toxicity, fails to counteract the lethal effect of LPS. This observation, together with the fact that linomide acts in the presence of excess amounts of GC receptor antagonist, indicates that linomide functions in a different way to that of known immunosuppressive agents like CsA and GC.     

The efficacy and efficiency of an in-vitro fertilization programme including embryo cryopreservation: a cohort study

A cohort of 485 couples starting their first in-vitro fertilization(IVF) attempt between January, 1989 and February, 1991 inclusive,were followed until June 1, 1992. A total of 1086 treatmentcycles were initiated (mean 2.2, range 1–6). Of these,235 (21.8%) cycles were cancelled, giving a total of 851 embryoreplacements (mean 1.7, range 1–5). After IVF treatment,189 women have either delivered or have an ongoing pregnancyin the second or third trimester. This gives a baby take-homerate of 17.4% per started cycle and 22.2% per embryo replacement.For 91 (18.6%) of the couples, the treatment was abandoned priorto completion of the three scheduled IVF attempts and 57 (11.7%)of these had no completed IVF cycles. In the group of coupleswith reduced sperm quality, the delivery rate was significantlylower than that of the other groups. A total of 193 women hadembryos cryopreserved in at least one IVF cycle; 124 of thesewomen started a frozen embryo replacement cycle and 88 had atleast one cycle with replacement of frozen/thawed embryos, resultingin 25 deliveries/ongoing pregnancies. Due to the Norwegian lawon assisted procreation 65 (33.7%) of the women have had theirfrozen embryos thawed and discarded after 12 months of storage.The cryopreservation programme, with the limitations of theNorwegian law, gives a 5.2% increase in the baby take-home ratefor women entering the IVF programme, an increase of 13.2% inthe number of ongoing pregnancies/deliveries and an 11.6% increasein number of children/viable fetuses. A total of 214 women havedelivered or have ongoing pregnancies in the second or thirdtrimester. This represents 44.1% of the 485 women accepted forIVF treatment, irrespective of whether they were treated ornot, and 50.0% of those couples who completed at least one IVFcycle.     

Lp(a) lipoprotein level predicts survival and major coronary events in the Scandinavian Simvastatin Survival Study

The Scandinavian Simvastatin Survival Study (4S) was a double-blind. randomized placebo-controlled multi-centre clinical trial of long-term Simvastatin therapy in patients with coronary heart disease who had total cholesterol levels between 5.5 and 8.0 mmol/1, comprising 4444 patients, equally distributed to a Simvastatin and a placebo group. Patients achieved a significant 30% relative reduction in overall mortality with Simvastatin therapy through a 42% relative reduction in coronary heart disease mortality. Lp(a) lipoprotein levels in Scandinavian coronary heart disease patients were strikingly higher than in healthy controls. Numbers of deaths in the Simvastatin group differed significantly between quartiles of Lp(a) lipoprotein levels, the reduction in deaths being most pronounced in the second (next to lowest) quartile. Subjects with major coronary events had significantly higher Lp(a) lipoprotein levels than subjects without such events, in all groups. The relationship between Lp(a) lipoprotein level and total mortality as well as between Lp(a) lipoprotein level and major coronary events was significantly different from zero, in logistic regression analyses. The findings show that Lp(a) lipoprotein predicts major coronary events as well as death in secondary prevention with Simvastatin. This prospective study provides independent confirmation that a high Lp(a) lipoprotein level is a significant coronary heart disease risk factor.     

Prostaglandin content in blood and lung tissue during alveolar hypoxia

The aim of the present work was to investigate whether prostaglandins (PGs) are synthetized and released from isolated blood-perfused rat and cat lungs secondary to vasoconstriction induced by alveolar hypoxia. The lungs were perfused with autologous blood with constant volume inflow via the pulmonary artery in a recirculating system. They were ventilated with constant volume positive pressure, and acute alveolar hypoxia was induced by ventilation with a gas containing 2% O₂. A superfusion bioassay technique was used to measure PG-like activity in the perfusate from the lungs, the blood being re-oxygenated before reaching the assay tissues. The oxygenator prevented the perfusate hypoxia induced by ventilation hypoxia to affect the bioassay tissues. The assay tissues were rat stomach strip, rat colon and chick rectum. They were sensitive to calibrating doses of 0.5–1 ng/ml PGE₂ and 1–2 ng/ml PGF_2α. In another series of experiments PGs of the F-series were measured in lung tissue from normoxic and hypoxic lungs with radioimmunoassay technique. No increase in PG-like activity could be detected in the venous effluent by means of bioassay during hypoxia, nor was the lung tissue content of immunoactive PGF increased by hypoxia. The present findings indicate that alveolar hypoxia does not stimulate PG-synthesis in lungs, refuting that PGs are important mediators of the pulmonary vasoconstrictor response to alveolar hypoxia. It is concluded that PGs play no significant role in producing the pressor response to alveolar hypoxia.     

The involvement of CD14 in stimulation of cytokine production by uronic acid polymers

In this study the molecular mechanisms behind the stimulatory activities of the uronic acid polymers poly mannuronic acid (poly M), high M alginate and oxidized cellulose (C60XY) were investigated and compared with lipopolysaccharide (LPS). The cytokine-inducing abilities of the uronic acid polymers and LPS were examined on CD14-positive human monocytes and CD14-negative U373 astrocytoma cells. It was found that LPS induced monocytes and U373 cells to produce tumor necrosis factor (TNF) and interleukin(IL)-6, respectively, by different mechanisms. The poly uronic acids induced monocytes to produce TNF, but with 100-1000 times less potency compared to LPS. On U373 cells, LPS at concentrations ? 32 ng/ml resulted in a dose-related IL-6 production, whereas the poly uronic acids had negligible effects even at 1 mg/ml. The binding data demonstrate that only the CD14-positive monocytes in the peripheral blood mononuclear cells population bound poly M. Furthermore, poly M was found to bind to CD14 in the presence of serum. Antibodies against CD14 also inhibited the TNF-inducing activity of the three uronic acid polymers tested. In conclusion, these results demonstrate that uronic acid polymers induce TNF production through mechanisms which involve CD 14.     

Binding of lipopeptide to CD14 induces physical proximity of CD14, TLR2 and TLR1

Lipoproteins or lipopeptides (LP) are bacterial cell wall components detected by the innate immune system. For LP, it has been shown that TLR2 is the essential receptor in cellular activation. However, molecular mechanisms of LP recognition are not yet clear. We used a FLAG-labeled derivative of the synthetic lipopeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R,S)-propyl]-(R)-cysteinyl-seryl-(lysyl)(3)-lysine (Pam(3)CSK(4)) to study the roles of CD14, TLR2 and TLR1 in binding and signaling of LP and their molecular interactions in human cells. The activity of Pam(3)CSK(4)-FLAG was TLR2 dependent, whereas the binding was enabled by CD14, as evaluated by flow cytometry and confocal microscopy. Using FRET and FRAP imaging techniques to study molecular associations, we could show that after Pam(3)CSK(4)-FLAG binding, CD14 and Pam(3)CSK(4)-FLAG associate with TLR2 and TLR1, and TLR2 is targeted to a low-mobility complex. Thus, LP binding to CD14 is the first step in the LP recognition, inducing physical proximity of CD14 and LP with TLR2/TLR1 and formation of the TLR2 signaling complex.