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Additional Doses (additional + dose)
Selected AbstractsDecrease in Langerhans Cells and Increase in Lymph Node Dendritic Cells Following Chronic Exposure of Mice to Suberythemal Doses of Solar Simulated RadiationPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 5 2005Pauline McLoone ABSTRACT Exposure of certain strains of mice to ultraviolet radiation (UVR) causes suppression of some innate and adaptive immune responses. One such consequence of acute UVB exposure is a reduction in the number of Langerhans cells (LC) in the epidermis and an increase in dendritic cells (DC) in lymph nodes draining the irradiated skin sites. Exposure to chronic UVB irradiation also has effects on the immune system, but it is unknown what effects are caused by repeated doses of solar simulated radiation (SSR). Consequently, the main aims of the present study were to determine whether repeated exposure to low doses of SSR would lead to similar changes in these cell populations and whether chronic doses of SSR activate a protective photoadaptation mechanism. Groups of C3H/HeN mice were irradiated daily with 3.7 J/cm2 SSR from Cleo Natural lamps for 2, 10, 20, 30 or 60 days. Further groups of mice received an additional dose of 7.4 J/cm2 SSR on days 2, 10, 30 or 60 to test for photoadaptation. The numbers of LC in the epidermis and DC in the lymph nodes draining irradiated skin sites were counted 24 h after the final irradiation. With the exception of mice irradiated for only 2 days, LC were significantly reduced throughout the chronic irradiation protocol, and no recovery occurred. DC numbers were significantly increased in the draining lymph nodes of mice irradiated for 20 days and 60 days. [source] Immunization with an adjuvant hepatitis B vaccine after liver transplantation for hepatitis B-related diseaseHEPATOLOGY, Issue 4 2003Ulrich Bienzle M.D. Patients who undergo transplantation for hepatitis B virus (HBV)-related diseases are treated indefinitely with hepatitis B hyperimmunoglobulin (HBIG) to prevent endogenous HBV reinfection of the graft. Active immunization with standard hepatitis B vaccines in these patients has recently been reported with conflicting results. Two groups of 10 liver transplant recipients on continuous HBIG substitution who were hepatitis B surface antigen (HBsAg) positive and HBV DNA negative before transplantation were immunized in a phase I study with different concentrations of hepatitis B s antigen formulated with the new adjuvants 3-deacylated monophosphoryl lipid A (MPL) and Quillaja saponaria (QS21) (group I/vaccine A: 20 ,g HBsAg, 50 ,g MPL, 50 ,g QS21; group II/vaccine B: 100 ,g HBsAg, 100 ,g MPL, 100 ,g QS21). Participants remained on HBIG prophylaxis and were vaccinated at weeks 0, 2, 4, 16, and 18. They received 3 additional doses of vaccine B at bimonthly intervals if they did not reach an antibody titer against hepatitis B surface antigen (anti-HBs) greater than 500 IU/L. Sixteen (8 in each group) of 20 patients (80%) responded (group I: median, 7,293 IU/L; range, 721,45,811 IU/L anti-HBs; group II: median, 44,549 IU/L; range, 900,83, 121 IU/L anti-HBs) and discontinued HBIG. They were followed up for a median of 13.5 months (range, 6,22 months). The vaccine was well tolerated. In conclusion, most patients immunized with the new vaccine can stop HBIG immunoprophylaxis for a substantial, yet to be determined period of time. (Hepatology 2003;38:811,819). [source] Effect of Repeated Doses of Ethanol on Hepatic Mg2+ Homeostasis and MobilizationALCOHOLISM, Issue 7 2007Andrew Young The acute administration of a first dose of ethanol (EtOH) to rat liver cells reduces the amount of Mg2+ extruded by a second dose of EtOH or the subsequent addition of adrenergic agonists. In contrast, the Mg2+ extrusion normally elicited by the ,1 -adrenergic or , -adrenergic agonist does not impair the Mg2+ mobilization induced by the subsequent addition of EtOH. Inhibition of EtOH metabolism by 4-methylpyrazole abolishes almost completely the Mg2+ extrusion induced by the first dose of EtOH, and partially enlarges that elicited by the second dose of alcohol or the subsequent adrenergic stimulation. Ethanol-treated liver cells stimulated by the adrenergic agonist show a reduced level of membrane-bound G,s as well as a reduced cellular cAMP content. Analysis of cellular Mg2+ distribution indicates that EtOH administration decreases the Mg2+ content of the cytoplasm, mitochondria, and endoplasmic reticulum to a comparable extent. These data indicate that acute EtOH administration directly impairs cellular Mg2+ homeostasis and also prevents a further Mg2+ mobilization by additional doses of alcohol or ,1 -adrenoceptor and , -adrenoceptor agonist by decreasing cytosolic and intraorganelle Mg2+ content and by affecting G-protein membrane distribution/signaling. [source] Pharmacokinetics of oral doxycycline and concentrations in body fluids and bronchoalveolar cells of foalsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2007A. WOMBLE The objective of this study was to determine the disposition of orally administered doxycycline in foals. Six healthy 4- to 8-week-old foals were used. Doxycycline was administered to each foal via the intragastric (IG) route at dosages of 10 and 20 mg/kg, in a cross-over design. After the first 10 mg/kg dose, five additional doses were administered at 12-h intervals. A microbiological assay was used to measure doxycycline activity in serum, urine, peritoneal fluid, synovial fluid, cerebrospinal (CSF), pulmonary epithelial lining fluid (PELF), and bronchoalveolar (BAL) cells. Following administration at 10 mg/kg, mean ± SD time to peak serum doxycycline activity (tmax) was 3.0 ± 1.2 h, maximum serum activity (Cmax) was 2.54 ± 0.27 ,g/mL, and terminal half-life (t1/2) was 8.5 ± 2.8 h. Administration at a dose of 20 mg/kg resulted in a significantly longer tmax (5.5 ± 1.8 h) as well as a tendency toward higher Cmax (2.89 ± 0.33 ,g/mL) and longer t1/2 (11.9 ± 2.6 h). After multiple IG doses, doxycycline activity in CSF was significantly lower than concurrent serum activity, whereas peritoneal fluid, synovial fluid, and BAL cell doxycycline activity was similar to concurrent serum activity. Doxycycline activity in urine and PELF was significantly higher than that found at other sites. Oral administration at a dosage of 10 mg/kg every 12 h would maintain serum, PELF, and BAL cell activity above the minimum inhibitory concentrations of Rhodococcus equi, , -hemolytic streptococci, and other susceptible bacterial pathogens for the entire dosing interval. [source] A short course of BG9588 (anti,CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritisARTHRITIS & RHEUMATISM, Issue 3 2003Dimitrios T. Boumpas Objective CD40,CD40 ligand (CD40L) interactions play a significant role in the production of autoantibodies and tissue injury in lupus nephritis. We performed an open-label, multiple-dose study to evaluate the safety, efficacy, and pharmacokinetics of BG9588, a humanized anti-CD40L antibody, in patients with proliferative lupus nephritis. The primary outcome measure was 50% reduction in proteinuria without worsening of renal function. Methods Twenty-eight patients with active proliferative lupus nephritis were scheduled to receive 20 mg/kg of BG9588 at biweekly intervals for the first 3 doses and at monthly intervals for 4 additional doses. Safety evaluations were performed on all patients. Eighteen patients receiving at least 3 doses were evaluated for efficacy. Results The study was terminated prematurely because of thromboembolic events occurring in patients in this and other BG9588 protocols (2 myocardial infarctions in this study). Of the 18 patients for whom efficacy could be evaluated, 2 had a 50% reduction in proteinuria without worsening of renal function. Mean reductions of 38.9% (P < 0.005), 50.1% (P < 0.005), and 25.3% (P < 0.05) in anti,double-stranded DNA (anti-dsDNA) antibody titers were observed at 1, 2, and 3 months, respectively, after the last treatment. There was a significant increase in serum C3 concentrations at 1 month after the last dose (P < 0.005), and hematuria disappeared in all 5 patients with significant hematuria at baseline. There were no statistically significant reductions in lymphocyte count or serum immunoglobulin, anticardiolipin antibody, or rubella IgG antibody concentrations after therapy. Conclusion A short course of BG9588 treatment in patients with proliferative lupus nephritis reduces anti-dsDNA antibodies, increases C3 concentrations, and decreases hematuria, suggesting that the drug has immunomodulatory action. Additional studies will be needed to evaluate its long-term effects. [source] Pediatric Procedural Sedation with Ketamine: Time to Discharge after Intramuscular versus Intravenous AdministrationACADEMIC EMERGENCY MEDICINE, Issue 2 2009Preeti Ramaswamy MBBS Abstract Objectives:, Ketamine is an attractive agent for pediatric procedural sedation. There are limited data on time to discharge comparing intramuscular (IM) vs. intravenous (IV) ketamine. The authors set out to determine whether IM or IV ketamine leads to quicker discharge from the emergency department (ED) and how side effect profiles compare. Methods:, All patients who had received ketamine IM or IV at a tertiary children's hospital ED during the 3-year study period (2004,2007) were identified. Prospective sedation registry data, retrospective medical records, and administrative data were reviewed for drug dosages, use of additional agents, time of drug administration to discharge, total ED time (triage to discharge), and adverse events. A subgroup analysis for patients requiring five or fewer sutures (short suture group) was performed. Results:, A total of 229 patients were enrolled (60% male) with median age of 2.8 years (IQR =1.8,4.3 years) and median weight of 15.7 kg (range = 8.7,74 kg). Ketamine was most frequently employed for laceration repair (80%) and foreign body removal (9%). Overall, 48% received ketamine IM and 52% received it IV. In the short-suture subgroup, 52% received ketamine IM, while 48% received it IV. Multivariate linear regression analysis determined time from drug administration to patient discharge as 21 minutes shorter for IV compared with IM administration, adjusted for age and number of additional doses (R2 = ,0.35; 95% CI = ,0.5 to ,0.19; p < 0.001). Total time in the ED (triage to discharge) comparing IV versus IM administration, adjusting for age and gender and number of additional doses, was not significantly different (p = 0.16). In the short-suture subgroup, time to discharge from administration was also shorter in the IV ketamine group (R2 = ,0.454; 95%CI = ,0.66 to ,0.25; p < 0.001) but similar for total time in ED (p = 0.16). Overall, adverse events occurred in 35% (95% CI = 27% to 45%) of the IM group and 20% (95% CI = 13% to 28%) of the IV group (p = 0.01). Only one patient required brief bag-mask ventilation. Conclusions:, In this institution, time from drug injection to discharge was shorter in the IV compared to IM ketamine group, both overall and for the short-suture group. However, time from triage to discharge was similar. [source] | ||||||||||