Scale-up of Adhesive Transdermal Drug Delivery Systems

Pharmaceutical Research -     

Early changes in hemoglobin and hematocrit levels after packed red cell transfusion in patients with acute anemia

BACKGROUND: Equilibration of hemoglobin concentration after transfusion has been estimated to take about 24 hours, but some studies have shown that earlier measurements reflect steady-state values in persons who have not bled recently. This study was aimed at assessing the changes over time in hemoglobin concentration after transfusion in acutely anemic patients because of recent bleeding. STUDY DESIGN AND METHODS: Thirty-two normovolemic patients recovering from an acute bleeding episode who were no longer thought to be bleeding and who received a 2- unit red cell transfusion were studied. At baseline and 15, 30, 60, and 120 minutes and 24 hours after transfusion, hemoglobin concentration and hematocrit values were measured. RESULTS: The administration of 2 units of packed red cells elicited a 24-hour increase of 22.4 +/− 6.8 g per L in hemoglobin concentration. Hemoglobin values were not different at any of the defined posttransfusion times. Hematocrit levels experienced similar changes over time. Agreement between 15-minute and 24-hour values was excellent, as only 6 percent of patients exhibited a clinically significant difference (> 6 g/L) between the hemoglobin measurements. CONCLUSION: Hemoglobin and hematocrit values rapidly equilibrate after transfusion in normovolemic patients who are recovering from an acute bleeding episode. This fact would allow a rapid assessment of the effects of transfusion and of the recurrence of bleeding in patients remaining at risk.     

L-arginine reverses the antinatriuretic effect of cyclosporin in renal transplant patients

BACKGROUND: Cyclosporin has been shown to facilitate renal vasoconstriction and to have an antinatriuretic effect. The existence of an interference of cyclosporin with the vasodilating properties of endothelium mediated by nitric oxide production could mediate these effects. On the other hand, the infusion of the nitric oxide precursor L-arginine has been shown to induce renal vasodilatation and to facilitate natriuresis in normal volunteers. We have investigated the renal effects of the administration of an infusion of L-arginine in renal transplant patients chronically treated with cyclosporin. To facilitate the analysis of the data the effects of the administration of a similar dose of cyclosporin on renal function during the infusion of a vehicle were also investigated during the administration of a vehicle of L-arginine. DESIGN: Ten male renal transplant patients, chronically treated with cyclosporin and with a stable renal function were studied during 2 consecutive days after the administration of the usual morning dose of cyclosporin. The first day they received an intravenous infusion of vehicle and the second the infusion of graded doses of L-arginine (50, 100, 150 mg/kg/h) during 3 consecutive h. RESULTS: The first day, after cyclosporin administration a significant fall (P < 0.01) was observed in natriuresis and kaliuresis in the absence of changes in renal plasma flow and glomerular filtration rate. After the administration of L-arginine significant (P < 0.01) increases of renal plasma flow, glomerular filtration rate, and natriuresis were seen. The increase in blood levels of cyclosporin after its administration did not differ between days 1 and 2. CONCLUSION: These results indicate that L-arginine facilitates renal vasodilatation and natriuresis in renal transplant patients. Furthermore, the observed increase in sodium excretion could indicate that L-arginine counteracts the antinatriuretic effect of cyclosporin.      

Evidence consistent with horizontal transfer of the gene (emm12) encoding serotype M12 protein between group A and group G pathogenic streptococci.

Human isolates of Lancefield group G streptococci harbor sequences homologous with the structural gene (emm) encoding M protein, a major virulence factor in Streptococcus pyogenes (a group A Streptococcus species). We used DNA-DNA hybridization, restriction endonuclease chromosomal profiling, and multilocus enzyme electrophoresis to examine genetic relationships between group A and group G streptococcal strains expressing homologous serologic type 12 M (M12) protein. All M12 group A strains studied had very similar restriction endonuclease genomic profiles and multilocus enzyme genotypes. In contrast, the restriction enzyme genomic profile and multilocus enzyme genotype of the M12 group G strain CS140 were strikingly different from those characterizing the M12 group A organisms. DNA-DNA hybridization studies revealed, on average, 57% genomic similarity between the M12 group A and group G strains. Taken together, our data demonstrate that a gene encoding M12 protein occurs in two highly divergent chromosomal backgrounds, a result suggesting that an episode of horizontal gene transfer and recombination has occurred between two streptococcal lineages.     

The Boston AIDS Survival Score (BASS): a multidimensional AIDS severity instrument.

OBJECTIVES: This study developed a new acquired immunodeficiency syndrome (AIDS) severity system by including diagnostic, physiological, functional, and sociodemographic factors predictive of survival. METHODS: Three-hundred five persons with AIDS in Boston were interviewed; their medical records were reviewed and vital status ascertained. RESULTS: Overall median (+/- SD) survival for the cohort from the first interview until death was 560 +/- 14.4 days. The best model for predicting survival, the Boston AIDS Survival Score, included the Justice score (stage 2 relative hazard [RH] = 1.25, 95% confidence interval [CI] = 0.80, 1.96; stage 3 RH = 1.76, 95% CI = 1.15, 2.70), a newly developed opportunistic disease score (Boston Opportunistic Disease Survival Score; stage 2 RH = 1.35, 95% CI = 0.90, 2.02; stage 3 RH = 2.10, 95% CI = 1.38, 3.18), and measures of activities of daily living (any intermediate limitations, RH = 1.84, 95% CI = 1.05, 3.21; any basic limitations, RH = 2.60, 95% CI = 1.44, 4.69). This model had substantially greater predictive power (R2 = .17, C statistic = .68) than the Justice score alone (R2 = .09, C statistic = .61). CONCLUSIONS: Incorporating data on clinically important events and functional status into a physiologically based system can improve the prediction of survival with AIDS.