Does physical exercise at the workplace have any effect on sick leave?

The objective of the study was to ascertain whether physical activity at the workplace reduces the amount of sick leave. The databases Medline and Spri-line, reference lists, and professional expertise were consulted for information on the subject. We included random controlled trials, and controlled trials studying the effect on sick leave of physical activity at the worksite. Four trials were identified, including one carried out in Norway. The small number of trials limits the value of any conclusions and highlights the need for more research. The results of the four trials do not indicate that physical activity at the workplace reduces sick leave.     

Paired human chorionic gonadotrophin determinations for the prediction of pregnancy outcome in assisted reproduction

The aim of this study was to determine the prognostic value of single and paired measurements of serum concentrations of human chorionic gonadotrophin (HCG) for successful pregnancy following in-vitro fertilization (IVF) and tubal embryo transfer (TET). We analysed serum HCG concentrations 15 and 22 days after IVF or TET in 198 conception cycles. Cut-off values of serum HCG were determined by a receiver operating characteristic (ROC) curve. On the basis of single HCG samples on day 15 (HCG15) after transfer, using a cut-off value of HCG15 = 150 mIU/ml, the sensitivity was 71% and the specificity was 77%. The positive predictive value (HCG15 > or = 150 mIU/ml indicating a normal pregnancy) was 89%, while the negative predictive rate (HCG15 < 150 mIU/ml indicating an abnormal pregnancy) was 51%. Patients with HCG15 < 150 mIU/ml but HCG22/HCG15 ratio > or = 15, still had a 90% chance of normal pregnancy. However, in patients with HCG15 < 150 mIU/ml and an HCG22/HCG15 ratio < 15, there was an 84% chance of an abnormal pregnancy. We conclude that a single HCG15 determination combined with the ratio of HCG22 to HCG15 has a higher diagnostic accuracy for prediction of pregnancy outcome than either analysis alone.     

Up-regulation of brain N-methyl-D-aspartate receptors following multiple intracerebroventricular injections of [D-Pen2, D-Pen5] enkephalin and [D-Ala2, Glu4]deltorphin II in mice

The effects of chronic administration of [D-Pen2, D-Pen5]enkephalin and [D-Ala2, Glu4]deltorphin II, the selective agonists of the delta 1- and delta 2-opioid receptors, on the binding of [3H]MK-801, a noncompetitive antagonist of the N-methyl-D-aspartate receptor, were determined in several brain regions of the mouse. Male Swiss-Webster mice were injected intracerebroventricularly (i.c.v.) with [D-Pen2, D-Pen5]enkephalin or [D-Ala2, Glu4]deltorphin II (20 micrograms/mouse) twice a day for 4 days. Vehicle injected mice served as controls. Previously we have shown that the above treatment results in the development of tolerance to their analgesic activity. The binding of [3H]MK-801 was determined in brain regions (cortex, midbrain, pons and medulla, hippocampus, striatum, hypothalamus and amygdala). At 5 nM-concentration, the binding of [3H]MK-801 was increased in cerebral cortex, hippocampus, and pons and medulla of [D-Pen2, D-Pen5]enkephalin treated mice. In [D-Ala2, Glu4]deltorphin II treated mice, the binding of [3H]MK-801 was increased in cerebral cortex and hippocampus. The changes in the binding were due to increases in the Bmax value of [3H]MK-801. It is concluded that tolerance to delta 1- and delta 2-opioid receptor agonists is associated with up-regulation of brain N-methyl-D-aspartate receptors, however, some brain areas affected differ with the two treatments. The results are consistent with the recent observation from this laboratory that N-methyl-D-aspartate receptors antagonists block tolerance to the analgesic action of delta 1- and delta 2-opioid receptor agonists.     

Development of male contraceptive vaccine--a perspective

Anti-disialoganglioside (GD2) monoclonal antibodies (MAbs) have been used in vivo for immunolocalization and in phase I and II trials to target disseminated neuroblastoma, the most common extracranial solid tumor in children. However, the efficacy of these first-generation MAbs is likely to be improved by using engineered anti-GD2 antibodies. The generation of single-chain antibody fragments (scFv) could be very helpful as these molecules can be further modified to produce recombinant molecules with pre-defined properties such as immunotoxins, chimeric, or bispecific antibodies. Thus, a scFv directed against GD2 (scFv 7A4) was cloned, sequenced, and expressed. Its binding properties were characterized and compared to that of the parental MAb 7A4. Nucleotide sequence analysis of the scFv 7A4 indicated that its VH region belongs to the V region IIID subgroup and the V kappa to the V region II subgroup. The scFv 7A4 bound to GD2+ neuroblastoma cell lines but not to GD2- cell lines or to GD2- cells isolated from peripheral blood. ELISA and thin-layer chromatography (TLC) indicated that it retained the anti-GD2 specificity, and exhibited a slight cross-reaction with GD3 as the parental MAb. This scFv makes it possible to develop new useful reagents through genetic engineering for adjuvant tumor therapy.     

The Dentin Disc surface: a plausible model for dentin physiology and dentin sensitivity evaluation

Dentin sensitivity (DS) is a painful clinical condition which may affect 8-35% of the population. Various treatment modalities have claimed success in relieving DS, although at present there does not appear to be a universally accepted desensitizing agent. Current opinion based on Br?nnstr?m's Hydrodynamic Theory would suggest that following exposure of the dentin surface (through attrition, abrasion, or erosion), the presence of open dentinal tubules, patent to the pulp, may be a prerequisite for DS. The concept of tubule occlusion as a method of dentin desensitization, therefore, is a logical conclusion from the hydrodynamic theory. The fact that many of the agents used clinically to desensitize dentin are also effective in reducing dentin permeability tends to support the hydrodynamic theory. This paper reviews the in vitro evaluation of desensitizing agents, the techniques used to characterize their effects on the prepared dentin surface, and the ability of these agents to reduce permeability through tubule occlusion, and presents recent findings from ongoing research based on the Pashley Dentin Disc model. It can be concluded that the use of this model to determine surface characteristics, and reductions in dentin permeability through tubule narrowing or occlusion, provides a useful screening method for evaluating potential desensitizing agents. Interpreting changes observed in vitro is difficult, and extrapolation to the clinical situation must be tempered with caution.     

Effects of tromethamine buffer on coagulation variables and ionized calcium concentration in dogs

OBJECTIVE: To evaluate coagulation variables in 2 groups of dogs after tromethamine administration. ANIMALS: 13 Beagles. PROCEDURES: Both groups of dogs received a 30-minute IV infusion of 10 ml of 0.3M tromethamine/kg of body weight. In unsedated dogs (group 1, n = 8), prothrombin time, activated partial thromboplastin time, normalized ionized calcium concentration, platelet numbers, and platelet function were measured prior to treatment, at the end of the infusion, and 1 hour after the infusion. In xylazine-sedated dogs (group 2, n = 5), buccal mucosal bleeding time and plasma percentage of von Willebrand factor antigen were measured before and 1 hour after infusion, and fibrin degradation products concentration was measured 1 hour after infusion. Platelet function was assessed by determining platelet aggregation and by measuring ATP release from the aggregating platelets over 6 minutes, using a whole blood aggregometer, with 20, 10, and 5 microM ADP and 5 and 10 micrograms of collagen/ml as platelet activation agonists. RESULTS: There was no significant change in any of the variables measured in either group of dogs, compared with baseline values. CONCLUSIONS AND CLINICAL RELEVANCE: When administered to healthy dogs, tromethamine does not change the coagulation indices measured.     

Suppression of human prostate carcinoma metastases in severe combined immunodeficient mice by interleukin 2 immunocytokine therapy

Immunocytokines are antibody-cytokine fusion proteins that combine the unique targeting ability of antibodies with the multifunctional activities of cytokines to activate effector cells in the tumor microenvironment. Here, we demonstrate the therapeutic efficacy of a tumor-specific immunocytokine, huKS1/4-IL2, which effectively inhibited growth and dissemination of lung and bone marrow metastases of human prostate carcinoma in severe combined immunodeficient mice. This antitumor effect was specific and highly effective, irrespective of reconstitution of these mice with human lymphokine-activated killer cells. Survival times of mice treated with huKS1/4-IL2 were increased 4-fold as compared with animals treated with a mixture of the corresponding antibody and recombinant human interleukin-2 (rhIL2). A persistent antitumor response after treatment with the huKS1/4-IL2 immunocytokine in B, T, and natural killer cell-deficient severe combined immuodeficient-BEIGE mice, depleted of granulocytes, implies a major role for macrophages in this treatment effect. Our data demonstrate that immunocytokine-directed interleukin-2 therapy to tumor sites is an immunotherapeutic approach with potent effects against disseminated metastases of human prostate carcinoma and suggest that this treatment could be effective in an adjuvant setting for patients with minimal residual disease.     

Effect of 7-nitroindazole on tolerance to morphine, U-50,488H and [D-Pen2, D-Pen5] enkephalin in mice

The effects of 7-nitroindazole (7-NI), an inhibitor of the neuronal nitric oxide synthase (nNOS) which does not increase blood pressure, on tolerance to the antinociceptive activity of mu-(morphine), kappa-(U-50,488H) and delta-([D-Pen2, D-Pen5]enkephalin, DPDPE) opioid receptor agonists were determined in mice. Male Swiss-Webster mice were made tolerant by twice daily injections of morphine (20 mg/kg, s.c.), U-50,488H (25 mg/kg, i.p.) or DPDPE (20 micrograms/mouse, i.c.v.) for 4 days. When tested on day 5, tolerance to their antinociceptive activity was evidenced by decreased response in chronic drug treated mice in comparison to vehicle-injected mice. Concurrent administration of 7-NI (20, 40 or 80 mg/kg, i.p.) with DPDPE did not modify the development of tolerance to the antinociceptive action of DPDPE. However, 7-NI (40 or 80 mg/kg, i.p.) inhibited the development of tolerance to the antinociceptive activity of morphine and U-50,488H but the lower dose of 7-NI (20 mg/kg, i.p.) was not effective. Chronic administration of 7-NI by itself did not modify the acute response to morphine, U-50,488H or DPDPE. It is concluded that a specific inhibitor of nNOS can inhibit tolerance to the antinociceptive activity of mu- and kappa- but not of delta-opioid receptor agonists in mice.     

Hemodynamic correlates of the third heart sound during the evolution of chronic heart failure

OBJECTIVES: The purpose of this study was to examine the temporal relation between the development of a third heart sound during the course of evolving heart failure and associated hemodynamic abnormalities. BACKGROUND: Although various theories have been proposed to explain the origin of the third heart sound, the exact origin of this sound remains unknown. METHODS: Studies were performed in seven dogs in which heart failure was produced by multiple sequential intracoronary micro-embolizations. Hemodynamic studies including ventriculography, pulsed wave Doppler echocardiography and intracardiac phonocardiography were performed at baseline, at the time at third heart sound was first heard and at 6 and 24 weeks after onset of the third heart sound. RESULTS: All dogs developed a third heart sound at 9 +/- 2 weeks after the initial embolization. The onset of the sound was accompanied by an increase in left ventricular chamber stiffness relative to the baseline value (0.25 +/- 0.03 vs. 0.14 +/- 0.01 mm Hg/ml) (p < 0.05) and mean deceleration of early mitral inflow velocity (1,040 +/- 90 vs. 590 +/- 40 cm/s per s) (p < 0.05). CONCLUSIONS: These data indicate that the onset of a third heart sound during the course of evolving heart failure occurs coincident with the development of increased left ventricular chamber stiffness and the manifestation of rapid deceleration of early mitral inflow velocity. These findings are consistent with a myocardial vibratory origin of this sound.     

Isolation of chromaffin cell thapsigargin-sensitive Ca2+ store in light microsomes from bovine adrenal medulla

1. A subcellular fractionation procedure for bovine adrenal glands was designed with the aim to study the biochemical properties of Ca2+ stores in chromaffin cells. 2. The thapsigargin-sensitive compartment of Ca2+ stores was found to be highly enriched in a light microsomal fraction (LMF) on a 15-30% linear sucrose gradient, and was found to be essentially devoid of contamination by plasma, mitochondrial or secretory granule membranes. 3. A Ca(2+)-pumping ATPase was identified in this LMF as a 97 kDa protein forming an acid-stable, Ca(2+)-dependent, thapsigargin-sensitive phosphorylated intermediate upon incubation with [gamma-32P]ATP, suggesting this protein to represent a SERCA-3 isoform of Ca2+ ATPases. 4. A major 162 kDa protein, previously demonstrated in the isolated chromaffin cells, was enriched in the LMF, distributing on sucrose gradients in parallel with the thapsigargin-sensitive Ca2+ uptake. 5. LMF appears to represent a part of the thapsigargin-sensitive Ca2+ store of chromaffin cells, and should be useful for further studies of the store properties at the subcellular and molecular level.