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Treatment Days (treatment + day)
Selected AbstractsEffects of buspirone and alprazolam treatment on the startle-potentiated startle responseDEPRESSION AND ANXIETY, Issue 3 2004Randall L. Commissaris Ph.D. Abstract The startle potentiated startle (SPS) paradigm has been reported to be an effective procedure for studying the conditioned enhancement of acoustic startle in the absence of electric shocks or extinction. This study examines the effects of two anxiolytic treatments, buspirone and alprazolam, on this SPS effect. Subjects were tested in the SPS paradigm 2 days a week (Monday and Thursday) for 10 weeks. Each startle test session consisted of 10 Noise Alone trials (115 dB acoustic noise burst presented for 40 ms) and 10 Light+Noise trials (115 dB acoustic stimuli presented during the latter 40 ms of a 3,540 ms period in which a 15-watt light was illuminated). Although there was no difference in startle amplitude on Noise Alone trials when compared to Light+Noise trials initially, by the end of the first test session and continuing throughout the duration of the experiment, startle amplitude on Light+Noise trials was significantly (approximately 50,75%) greater than on Noise Alone trials. After five control (i.e., no injection) SPS test sessions, once-weekly drug challenges were conducted over the course of 7 weeks. In these weekly drug challenges, subjects received acute treatment with various doses of the benzodiazepine anxiolytic alprazolam (0.25, 0.5, 1.0 mg/kg) or the novel anxiolytic buspirone (1.0, 2.0, 4.0 mg/kg); subjects also received vehicle treatment (0.5% methylcellulose) on one treatment day. All treatments were administered intraperitoneally (IP), 15 min before the start of startle testing. Consistent with previous reports, buspirone increased and alprazolam decreased startle amplitude on the Noise Alone trials; these effects were dose-related. Both agents reduced the magnitude of the SPS effect when it was expressed as the Light+Noise startle amplitude minus the Noise Alone startle amplitude. These findings are similar to the effects of these treatments in the traditional shock-based fear-potentiated startle paradigm. Depression and Anxiety 19:146,151, 2004. © 2004 Wiley-Liss, Inc. [source] Use of Chronic Epilepsy Models in Antiepileptic Drug Discovery: The Effect of Topiramate on Spontaneous Motor Seizures in Rats with Kainate-induced EpilepsyEPILEPSIA, Issue 1 2005Heidi L. Grabenstatter Summary:,Purpose: Potential antiepileptic drugs (AEDs) are typically screened on acute seizures in normal animals, such as those induced in the maximal electroshock and pentylenetet-razole models. As a proof-of-principle test, the present experiments used spontaneous epileptic seizures in kainate-treated rats to examine the efficacy of topiramate (TPM) with a repeated-measures, crossover protocol. Methods: Kainic acid was administered in repeated low doses (5 mg/kg) every hour until each Sprague,Dawley rat experienced convulsive status epilepticus for >3 h. Six 1-month trials (n = 6,10 rats) assessed the effects of 0.3,100 mg/kg TPM on spontaneous seizures. Each trial involved six pairs of TPM and saline-control treatments administered as intraperitoneal injections on alternate days with a recovery day between each treatment day. Data analysis included a log transformation to compensate for the asymmetric distribution of values and the heterogeneous variances, which appeared to arise from clustering of seizures. Results: A significant effect of TPM was observed for 12 h (i.e., two 6-h periods) after a 30-mg/kg injection, and full recovery from the drug effect was complete within 43 h. TPM exerted a significant effect at doses of 10, 30, and 100 mg/kg, and the effects of TPM (0.3,100 mg/kg) were dose dependent. Conclusions: These data suggest that animal models with spontaneous seizures, such as kainate- and pilocarpine-treated rats, can be used efficiently for rapid testing of AEDs with a repeated-measures, crossover protocol. Furthermore, the results indicate that this design allows both dose,effect and time-course-of-recovery studies. [source] A dose escalation study of YM150, an oral direct factor Xa inhibitor, in the prevention of venous thromboembolism in elective primary hip replacement surgeryJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2007B. I. ERIKSSON Summary.,Background:,YM150, a new oral direct factor Xa inhibitor is used as prophylaxis for venous thromboembolism (VTE), a well-known risk after orthopaedic surgery. Objectives:,To assess the safety and efficacy of thromboprophylaxis with YM150 in a dose escalation study. Patients/methods:,Patients (174) undergoing hip replacement surgery were randomized per cohort to oral once daily YM150 or subcutaneous enoxaparin (40 mg daily) in a 4:1 ratio for 7,10 days treatment. The YM150 doses were 3, 10, 30 and 60 mg by sequential four-dose escalation cohorts. The primary endpoint was major and/or clinically relevant non-major bleeding. The incidence of VTE was defined as a composite of verified symptomatic events and/or positive findings at bilateral venography on the last treatment day. An independent adjudication committee evaluated blindly the outcomes of the open-label study. Results:,No major and three clinically relevant non-major bleeds were reported, 1 (2.9%; 95% CI, 0.1,15.1) in the 3 mg and 2 (5.7%; 95% CI, 1.0,18.8) in the 10 mg YM150 dose groups. Of 147 patients (84%) with an evaluable venogram, VTE was observed in 51.9% (95% CI, 31.9,71.4), 38.7% (95% CI, 22.6,57.0), 22.6% (95% CI, 9.7,39.4), and 18.5% (95% CI, 7.5,36.5) in the YM150 dose groups 3, 10, 30 and 60 mg, respectively. A significant YM150 dose-related trend in VTE incidence was found (P=0.006). VTE with enoxaparin was 38.7% (95% CI, 22.6,57.0). Conclusions:,YM150, 10,60 mg daily, starting 6,10 h after primary hip replacement, was shown to be safe, well tolerated and effective. [source] The efficacy of dantrolene sodium in controlling exertional rhabdomyolysis in the Thoroughbred racehorseEQUINE VETERINARY JOURNAL, Issue 7 2003J. G. T. Edwards Summary Reasons for performing study: Dantrolene sodium (Dantrium) has been used extensively for the treatment of myopathies in man and anecdotal evidence suggests it is of clinical benefit in the control of exercise-induced rhabdomyolysis (ER) in racehorses, although data to support this are currently lacking. Objectives: To investigate the efficacy of oral dantrolene sodium in controlling ER in a randomised, double-blind, placebo-controlled crossover trial involving 77 Thoroughbred racehorses in Newmarket, UK. Methods: Horses were treated on 2 occasions 1 week apart, with treatment days coinciding with a return to exercise following 2 days box rest on each occasion. For the first treatment, each horse was randomly selected to receive either 800 mg dantrolene sodium or a colour- matched placebo administered orally 1 h before exercise. This was followed by crossover to the other treatment on the second occasion, with each horse thereby acting as its own control. Degree of ER was assessed using rising serum creatine kinase (CK) levels, by subtracting pre-exercise blood CK levels from those measured in 6 h post exercise blood samples. For each horse, the difference in change between pre- and post exercise CK values between placebo and dantrolene treatments was calculated, with positive values indicating a greater rise with placebo than with dantrolene sodium treatment. Results: The overall mean difference for all horses was +104.8 iu/l and the null hypothesis, that there was no true difference in non-normally distributed post exercise rises in CK values between placebo and dantrolene treatments, was rejected (P = 0.0013) using the nonparametric Wilcoxon signed rank test. Additionally, no horses given dantrolene sodium showed clinical signs of ER, whereas 3 horses given the placebo developed ER following exercise. The incidence of ER in the study was 4% (3/77). Conclusions: The results confirmed that oral administration of dantrolene sodium, 1 h before exercise, had a statistically significant effect on reducing the difference between pre - and post exercise plasma CK levels compared with a placebo in the same animals, and preventing clinical ER in susceptible individuals. Potential relevance: This study suggested that dantrolene sodium is of use in controlling ER in the Thoroughbred racehorse. Further investigation into pre- and post exercise myoplasmic calcium levels and the repeat of the study late in the season when horses receive a much higher energy ration and more strenuous exercise would appear to be warranted. [source] BRIEF COMMUNICATIONS: A quantity survey of intravenous administration of metronidazole in its different forms in a tertiary teaching hospitalINTERNAL MEDICINE JOURNAL, Issue 8 2010L. L. Lee Abstract The aim of this paper is to examine the prescribing patterns and cost of various formulations of metronidazole in a hospital setting over a 3-month period. Oral metronidazole has high bioavailability (98.9%) with peak plasma concentrations averaged at 2.3 h after dosing. Despite the high bioavailability of oral metronidazole, many patients continue to receive metronidazole intravenously when they are suitable for oral preparation. An audit of 120 consecutive patients prescribed metronidazole was conducted at the Liverpool Hospital, NSW, from March to July 2005. There were 65 men and 55 women (age 18,93). Of the 120 patients, 16 were on oral, 1 on rectal and 103 were on intravenous metronidazole. Treatment was initiated based on clinical diagnoses. Potential pathogens were subsequently identified on only 21 occasions. The use of metronidazole as an oral preparation was contraindicated in 27 patients (22.5%) who were nil-by-mouth. Of these, rectally administered metronidazole was contraindicated in only eight patients. The average course of intravenous metronidazole was 8.0 ± 9.7 days (mean ± SD). The total number of intravenous metronidazole treatment days was 824. Oral metronidazole would have been possible in 618 out of the 824 days. The estimated cost to administer each dose of oral, suppository and intravenous forms of metronidazole is $A0.11, $A1.34 and $A6.09 respectively. Thus, substantial savings could be achieved if oral metronidazole were to be administered whenever possible. The early use of oral or rectal metronidazole should be encouraged when there are no clinical contraindications. [source] Evaluation of Side Effects and Patients' Perceptions during Tooth BleachingJOURNAL OF ESTHETIC AND RESTORATIVE DENTISTRY, Issue 6 2007RALPH H. LEONARD JR. DDS ABSTRACT Objective:, The objective of this nightguard vital bleaching (NGVB) study was to compare tooth sensitivity (TS), gingival irritation (GIr), and other side effects, as well as patients' perceptions during tooth bleaching, from treatment with experimental 5 and 7% hydrogen peroxide (HP) bleaching solutions with those of a commercially available 10% carbamide peroxide (CP) product. Materials and Methods:, Sixty-one participants completed the study wearing a scalloped maxillary treatment tray without reservoirs with the different concentrations of bleaching gels for 30 minutes twice a day for 7 days. Parameters evaluated were changes in gingival index (GI), nonmarginal gingival index, nongingival oral mucosal index, and tooth vitality. Participants were seen pretreatment, after 7 treatment days, and 1 week post-treatment. A daily log form to record TS and GIr was completed by each participant as well as a sensitivity questionnaire at each appointment. Additionally, at 10 months post-treatment, a questionnaire was sent to the participants concerning TS and GIr relative to the treatment process. Results:, Data from end-of-treatment questionnaires, daily log forms, and clinical examination revealed a statistical difference (p, 0.05) in the patients' ranking of and days of TS and GIr between group S (7% HP) and group T (10% CP, control group) at the end of active treatment. There also existed a statistical clinical change in the GI levels for groups R and S compared with the control group T. There was no statistical difference (p > 0.05) in any of the parameters evaluated among the three products at 7 days or 10 months post-treatment. Conclusions:, Participants in group S reported significantly more TS, GIr, and days of each compared with the control. There also existed a significant clinical change in the GI levels for groups R and S compared with the control group T. There was no significant difference among the three products at 7 days post-treatment. After ending treatment, TS/GIr was resolved in 2 to 3 days and did not recur during the 10 months post-treatment. CLINICAL SIGNIFICANCE The experimental HP bleaching solutions, as described in this study, can be used in NGVB with no long-term side effects as evaluated in this study for up to 10 months post-treatment. (J Esthet Restor Dent 19:355,366, 2007) [source] Postoperative analgesic efficacy of meloxicam compared to tolfenamic acid in cats undergoing orthopaedic surgeryJOURNAL OF SMALL ANIMAL PRACTICE, Issue 10 2010P. J. Murison Objectives: To investigate the efficacy of meloxicam or tolfenamic acid administered preoperatively and postoperatively (five days in total) to cats undergoing surgical fracture repair. Methods: Eighty-eight otherwise healthy cats were matched according to fracture site and then randomly allocated to one of two groups, receiving 0·2 mg/kg meloxicam by subcutaneous injection (group M) or 1·5 to 3 mg/kg tolfenamic acid orally (group T) before anaesthesia. Analgesia was continued with 0.05 mg/kg oral meloxicam once daily or 1·5 to 3 mg/kg oral tolfenamic acid twice daily for four days postoperatively. Pain was assessed by a blinded observer using visual analogue scales and a functional limb score. The drug administrator assessed feed intake and palatability of the treatment. Results: Data from 66 cats were analysed. Visual analogue scale pain scores and functional limb scores decreased over time in both groups but were not significantly different between treatments. Feed intake was similar in both groups. Meloxicam was significantly more palatable than tolfenamic acid on all treatment days. Clinical Significance: Meloxicam and tolfenamic acid demonstrated comparable analgesia, without clinically observable side effects. Meloxicam may be associated with superior compliance in clinical practice due to the higher palatability and once daily treatment resulting in better ease of administration. [source] Blood concentrations, tolerability and efficacy of pimecrolimus cream 1% in Japanese infants and children with atopic dermatitisTHE JOURNAL OF DERMATOLOGY, Issue 4 2007Lawrence F. EICHENFIELD ABSTRACT Pimecrolimus cream 1% is a topical calcineurin inhibitor for the treatment of atopic dermatitis. Minimal systemic exposure to pimecrolimus has been previously observed in Caucasian pediatric patients treated with the cream twice daily for up to 1 year. The objective of this open-label, non-comparative, multicenter study was to assess the systemic exposure, tolerability and efficacy of pimecrolimus cream 1% when used twice daily for 3 weeks in pediatric patients of Japanese background. The patient cohort consisted of 17 Japanese infants and children (age range, 3.6 months to 11.6 years) with atopic dermatitis of at least mild severity affecting ,10% of the total body surface area (range, 10,48%). Pimecrolimus cream 1% was applied twice daily for 3 weeks. Blood levels of pimecrolimus were determined on days 1, 10 and 22. Safety and tolerability were evaluated by monitoring adverse events, laboratory parameters, physical condition and vital signs. Efficacy parameters included the Eczema Area and Severity Index, the Investigators' Global Assessment and the pruritus score. The median exposure to pimecrolimus cream 1% was 22 treatment days (range, 9,29 treatment days). Pimecrolimus blood concentrations were <0.5 ng/mL in 94% of samples on day 1, in 93% of samples on day 10 and in 100% of samples on day 22, with no indication of an increase with increasing body surface area treated (up to 48% of the total body surface area). No drug-related systemic adverse events or serious adverse events were reported. Treatment was effective according to all efficacy parameters. The findings of this study indicate that the use of pimecrolimus cream 1% results in minimal systemic absorption of the active ingredient in pediatric patients of Japanese background with extensive disease. [source] Treatment of Acute Renal Failure in the Intensive Care Unit: Lower Costs by Intermittent Dialysis Than Continuous Venovenous HemodiafiltrationARTIFICIAL ORGANS, Issue 8 2009Stefan Farese Abstract Intermittent and continuous renal replacement therapies (RRTs) are available for the treatment of acute renal failure (ARF) in the intensive care unit (ICU). Although at present there are no adequately powered survival studies, available data suggest that both methods are equal with respect to patient outcome. Therefore, cost comparison between techniques is important for selecting the modality. Expenditures were prospectively assessed as a secondary end point during a controlled, randomized trial comparing intermittent hemodialysis (IHD) with continuous venovenous hemodiafiltration (CVVHDF). The outcome of the primary end points of this trial, that is, ICU and in-hospital mortality, has been previously published. One hundred twenty-five patients from a Swiss university hospital ICU were randomized either to CVVHDF or IHD. Out of these, 42 (CVVHDF) and 34 (IHD) were available for cost analysis. Patients' characteristics, delivered dialysis dose, duration of stay in the ICU or hospital, mortality rates, and recovery of renal function were not different between the two groups. Detailed 24-h time and material consumption protocols were available for 369 (CVVHDF) and 195 (IHD) treatment days. The mean daily duration of CVVHDF was 19.5 ± 3.2 h/day, resulting in total expenditures of ,436 ± 21 (21% for human resources and 79% for technical devices). For IHD (mean 3.0 ± 0.4 h/treatment), the costs were lower (,268 ± 26), with a larger proportion for human resources (45%). Nursing time spent for CVVHDF was 113 ± 50 min, and 198 ± 63 min per IHD treatment. Total costs for RRT in ICU patients with ARF were lower when treated with IHD than with CVVHDF, and have to be taken into account for the selection of the method of RRT in ARF on the ICU. [source] Bioequivalence evaluation of two brands of ketoconazole tablets (Onofin-K® and Nizoral®) in a healthy female Mexican populationBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 5 2004G. Marcelín-Jiménez Abstract A randomized, crossover study was conducted in 24 healthy female volunteers to compare the bioavailability of two brands of ketoconazole (200 mg) tablets; Onofin-K® (Farmacéuticos Rayere S.A., México) as the test and NIZORAL® (Janssen-Cilag, México) as the reference products. The study was performed at the Clinical Pharmacology Research Center of the Hospital General de México in Mexico City. Two tablets (400 mg) were administered as a single dose with 250 ml of water after a 12 h overnight fast on two treatment days separated by a 1 week washout period. After dosing, serial blood samples were collected for a period of 12 h. Plasma harvested was analysed for ketoconazole by a modified and validated HPLC method with UV detection in the range 400,14000 ng/ml, using 200 µl of plasma in a full-run time of 2.5 min. The pharmacokinetic parameters AUC0,t, AUC0,,, Cmax, Tmax and t1/2 were determined from plasma concentrations of both formulations and the results discussed. AUC0,t, AUC0,, and Cmax were tested for bioequivalence after log transformation of data, and no significant differences were found either in 90% classic confidence interval or in the Anderson and Hauck test (p<0.05). Based on statistical analysis, it is concluded that Onofin-K® is bioequivalent to Nizoral®. Copyright © 2004 John Wiley & Sons, Ltd. [source] Bioequivalence assessment of Azomycin® (Julphar, UAE) as compared to Zithromax® (Pfizer, USA),two brands of azithromycin,in healthy human volunteersBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2001Naji M. Najib Abstract Two studies have been performed to assess the relative bioavailability of Azomycin® (Julphar, UAE) as compared with Zithromax® (Pfizer, USA) at the International Pharmaceutical Research Center (IPRC), Amman, Jordan. One study involved Azomycin® capsules and the other Azomycin® suspension. Each study enrolled 24 volunteers and in both studies, after an overnight fasting, the two brands of azithromycin were administered as single dose on two treatment days separated by a 2 weeks washout period. After dosing, serial blood samples were collected for a period of 192 h. Plasma harvested from blood, was analysed for azithromycin by HPLC coupled with electrochemical detection. Various pharmacokinetic parameters including AUC0,t, AUC0,,,Cmax, Tmax, T1/2 and Kelm were determined from plasma concentrations for both formulations and found to be in good agreement with the reported values. AUC0,t, AUC0,, and Cmax were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence intervals for the test/reference ratios of these parameters were found within the bioequivalence acceptance range of 80,125%. Based on these statistical inferences it was concluded that Azomycin® capsule is bioequivalent to Zithromax® capsule and Azomycin® suspension is bioequivalent to Zithromax® suspension. Copyright © 2001 John Wiley & Sons, Ltd. [source] | ||||||||||