Effect of hepatic dysfunction on oral cyclosporin pharmacokinetics in marrow transplant patients

The effect of hepatic dysfunction, defined as abnormal serum bilirubin level, on oral cyclosporin (CSP) pharmacokinetics was examined in 28 marrow transplant patients who received CSP for prophylaxis of graft-v- host disease. Serum CSP concentrations were measured by radioimmunoassay. Forty-one concentration-time courses were studied, divided among patients with no (less than 1.2 mg/dL), mild (1.2 to 2.0 mg/dL), and moderate (2.0 to 5.0 mg/dL) hepatic dysfunction. CSP elimination, as determined by elimination rate constant and clearance, was delayed in patients with moderate hepatic dysfunction compared to those with no hepatic dysfunction (P less than .05). The volume of distribution, lag time for absorption, maximum serum concentration, and time at which the maximum concentration was achieved was not affected by hepatic function. These data indicate that patients with moderate hepatic dysfunction have delayed CSP or CSP metabolite elimination and may be at higher risk for developing CSP-related toxicity.     

A monokine regulates colony-stimulating activity production by vascular endothelial cells

Human umbilical vein endothelial cells were cultured in supernatants of peripheral blood monocytes that had been cultured for 3 days with and without lactoferrin. Colony-stimulating activity (CSA) was measured in supernatants of the endothelial cell cultures and appropriate control cultures using normal, T-lymphocyte-depleted, phagocyte-depleted, low- density bone marrow cells in colony growth (CFU-GM) assays. Monocyte- conditioned medium contained a nondialyzable, heat labile factor that enhanced 4-15--fold the production of CSA by endothelial cells. The addition of lactoferrin to monocyte cultures reduced the activity of this monokine by 69%. Lactoferrin did not inhibit CSA production by monokine-stimulated endothelial cells. Therefore, vascular endothelial cells are potent sources of CSA, the production of CSA by these cells is regulated by a stimulatory monokine, and the production and/or release of the monokine is inhibited by lactoferrin, a neutrophil- derived putative feedback inhibitor of granulopoiesis. Inasmuch as a similar monokine is known to stimulate CSA production by fibroblasts and T lymphocytes, we suggest that mononuclear phagocytes play a pivotal role in the regulation of granulopoiesis by recruiting a variety of cell types to produce CSA.     

Health impacts of family planning

Among the many effects of family planning is the influence ithas on mortality and morbidity in women and children throughthe mechanism of changing the number and spacing of children.There is a complex set of relationships between mother's age,parity, birth spacing and infant and child mortality and morbidity.Much effort has been put into untangling this web in the hopeof identifying clear causal connections, but for the most parton the basis of inadequate data. Rather than attempt to establishthe relative importance of child spacing as a cause of decreasesin mortality, this paper takes as its starting point that thereis a connection, and presents some possible causal mechanismswhich explain how short birth intervals and child mortalitycould be related. In addition the most frequently cited hypotheses-maternaldepletion and sibling competition-a third is examined-birthcrowding which, it is suggested, influences the pattern of thetransmission of infectious diseases and, in turn, mortality. In the field of maternal mortality, the data which could beused to quantify the benefits of family planning are in evenshorter supply; however, the causal connections are rather moreeasily identified. The final section combines parity-specificdata on maternal mortality with evidence of changes in fertilitypatterns brought about by family planning to assess how successfulwe can hope to be in reducing through birth control the numberof women who die in childbirth.     

Translation, adaptation, and validation of the Brazilian version of the Marijuana Expectancy Questionnaire

This study presents the translation and validation of the Marijuana Expectancy Questionnaire (MEQ-Brazilian Adaptation), which evaluates the expectancy of results in marijuana use, important for treatment and prognosis related to addiction to this substance. The sample consisted of 400 subjects, 217 males and 183 females, of whom 147 were marijuana users and 253 were non-users. In the user group, 90 subjects were marijuana-dependent. Semantic validation of the MEQ-Brazilian Adaptation was confirmed after evaluation and suggestions by an expert review panel. In the Brazilian sample, 78 items were applied; however, the decision was made for a statistical analysis using the reduced scale (55 items), with similar psychometric properties. For both scales, an alpha = 0.89 was obtained. Discriminant validation of the reduced scale was statistically significant (p = 0.001). Temporal stability was examined using a 123-subject sample with a one-week interval between test and retest, indicating that the instrument obtains a consistent response pattern over time (r = 0.990). MEQ-Brazilian Adaptation presented good psychometric results and can be used in studies that aim to evaluate expectancy of results related to marijuana use.     

Acute silver toxicity in the euryhaline copepod Acartia tonsa: influence of salinity and food

The euryhaline copepod Acartia tonsa was exposed to silver (AgNO(3)) in either the absence or the presence of food (diatom Thalassiosira weissflogii; 2 x 10(4) cells/ml). Standard static-renewal toxicity tests that included a fixed photoperiod of 16: 8 h light:dark and temperature (20 degrees C) were run in three different salinities (5, 15, and 30 ppt) together with measurements of pH, ions (Na(+), Cl(-), K(+), SO(4)(2-), Mg(2+), and Ca(2+)), alkalinity, dissolved organic carbon, and total and dissolved (0.45 microm) silver concentrations in the experimental media. In the absence of food, the 48-h EC50 (concentration causing effect to 50% of the individuals tested) values based on total and dissolved silver concentrations were 11.6, 87.2, and 163.2 microg Ag/L and 7.1, 79.2, and 154.6 microg Ag/L at salinities 5, 15, and 30 ppt, respectively. In the presence of food, they were 62.1, 98.5, and 238.4 microg Ag/L and 48.4, 52.3, and 190.9 microg Ag/L, respectively. In all experimental conditions, most of the toxic silver fraction was in the dissolved phase, regardless of salinity or the presence of food in the water. In either the absence or the presence of food, acute silver toxicity was salinity dependent, decreasing as salinity increased. Data indicate that changes in water chemistry can account for the differences in acute silver toxicity in the absence of food, but not in the presence of food, suggesting that A. tonsa requires extra energy to cope with the stressful conditions imposed by acute silver exposure and ionoregulatory requirements in low salinities. These findings indicate the need for incorporation of both salinity and food (organic carbon) in a future biotic ligand model (BLM) version for estuarine and marine conditions, which could be validated and calibrated using the euryhaline copepod A. tonsa.