Lorazepam for the prevention of recurrent seizures related to alcohol. (1/211)

BACKGROUND AND METHODS: Alcohol abuse is one of the most common causes of seizures in adults. In a randomized, double-blind study, we compared lorazepam with placebo for the prevention of recurrent seizures related to alcohol. Over a 21-month period, we studied consecutive patients with chronic alcohol abuse who were at least 21 years of age and who presented to the emergency departments of two hospitals in Boston after a witnessed, generalized seizure. The patients were randomly assigned to receive either 2 mg of lorazepam in 2 ml of normal saline or 4 ml of normal saline intravenously and then observed for six hours. The primary end point was the occurrence of a second seizure during the observation period. RESULTS: Of the 229 patients who were initially evaluated, 186 met the entry criteria. In the lorazepam group, 3 of 100 patients (3 percent) had a second seizure, as compared with 21 of 86 patients (24 percent) in the placebo group (odds ratio for seizure with the use of placebo, 10.4; 95 percent confidence interval, 3.6 to 30.2; P<0.001). Forty-two percent of the placebo group were admitted to the hospital, as compared with 29 percent of the lorazepam group (odds ratio for admission, 2.1; 95 percent confidence interval, 1.1 to 4.0; P=0.02). Seven patients in the placebo group and one in the lorazepam group were transported to an emergency department in Boston with a second seizure within 48 hours after hospital discharge. CONCLUSIONS: Treatment with intravenous lorazepam is associated with a significant reduction in the risk of recurrent seizures related to alcohol.  (+info)

Measuring reproducibility of regional brain metabolic responses to lorazepam using statistical parametric maps. (2/211)

Statistical parametric mapping (SPM) is a method for localizing differences in brain activation patterns without the need for anatomic predefined constraints. The purpose of this study was to assess the reproducibility of the patterns of activation obtained with SPM for baseline measures and for metabolic changes in response to lorazepam on a test-retest design. The results were compared with those we previously published using region-of-interest (ROI) methods. METHODS: Sixteen healthy right-handed men were scanned twice with PET and [18F]fluorodeoxyglucose (FDG): before placebo and before lorazepam (30 microg/kg). The same double FDG procedure was repeated 6-8 wk later to assess test-retest reproducibility. Image datasets were analyzed by using SPM95 software. Difference images between baseline and lorazepam were compared for the first and second evaluations, both for relative decreases as well as increases in metabolism. Significance level was systematically varied to P < 0.001, P < 0.01 and P < 0.05. RESULTS: There were no differences in the baseline SPM maps obtained for the first and second evaluations. SPM showed similar, although not identical, differences in response to lorazepam between the two evaluations. Both evaluations showed significant decreases in occipital cortex (9.7% and 10%) and significant relative increases in left temporal pole (6.8% and 10.4%). However, the second evaluation showed a decrease in the left frontal cortex (areas 6 and 8), which was not present in the first evaluation. The results were very similar to those we had obtained with ROI methods, except for the activation in the left temporal pole, which we had not observed with ROI analyses. CONCLUSION: Although the overall pattern of lorazepam-induced activation depicted by SPM was reproducible in pattern and magnitude, there were some differences that included a left frontal area of deactivation during the second but not the first evaluation. Results with SPM are similar to those with the ROI method, and, because it systematically analyses the whole brain, SPM can uncover patterns not seen with the ROI method.  (+info)

Drug discrimination analysis of partial agonists at the benzodiazepine site. I. Differential effects of U-78875 across training conditions in baboons and rats. (3/211)

The benzodiazepine receptor ligand U-78875 [3-(5-cyclopro pyl-1,2, 4-oxadiazol-3-yl)-5-(1-methylethyl)imidazol(1, 5-a)quinoxalin-4(5H)-o-ne] was studied in rats trained to discriminate i.p. 1.0 mg/kg lorazepam, 1.0 mg/kg diazepam, or 10 mg/kg pentobarbital, and baboons trained to discriminate oral 1.8 mg/kg lorazepam or 10 mg/kg pentobarbital. U-78875 doses were 0.01 to 10 mg/kg i.p. in rats and 0.32 to 56 mg/kg orally in baboons. U-78875 occasioned drug-appropriate responding in pentobarbital-trained (ED50 = 1.8 mg/kg) and diazepam-trained (ED50 = 0.056 mg/kg) rats, but it occurred in only one pentobarbital-trained baboon and not in the majority of lorazepam-trained baboons or rats. In baboons that generalized to U-78875, discriminative effects were antagonized by flumazenil. The interaction of U-78875 with pentobarbital, diazepam, and lorazepam revealed further differences in its behavioral effects. U-78875 potentiated the effects of pentobarbital, even in baboons that did not generalize to U-78875, but U-78875 had little effect in combination with diazepam. In lorazepam-trained animals that did not generalize to it, U-78875 antagonized lorazepam's effects, but U-78875 neither antagonized nor potentiated lorazepam in animals that did generalize to U-78875. Thus, although U-78875 generally functioned as a benzodiazepine agonist in pentobarbital- and diazepam-trained animals, its unique effects in lorazepam-trained animals appear to reflect its in vitro profile as a partial agonist.  (+info)

Effects of a benzodiazepine, lorazepam, on motion integration and segmentation: an effect on the processing of line-ends? (4/211)

Previous studies have shown that the perceptual integration of component motions distributed across space is inhibited whenever segmentation cues, such as line-ends, are salient. Herein, we investigate to what extent enhanced inhibition induced by lorazepam, a benzodiazepine facilitating the fixation of GABA on GABAA receptors, modifies the balance between motion integration and motion segmentation at the behavioural level. Motion integration was tested in 16 healthy volunteers taking a single and oral dose of either placebo or lorazepam (0.038 mg kg-1). The stimulus consisted of an outlined diamond presented behind four, otherwise invisible, apertures and translating along a circular trajectory (Lorenceau & Shiffrar (1992). Vision Research, 32, 263-273). Under these conditions, recovering the global diamond direction requires the integration of the component motions available within each aperture. The observers were asked to discriminate the global, clockwise or counter-clockwise, diamond direction under difficult--at high luminance contrasts--or easy--at low luminance contrasts--conditions. Overall, reaction times and error rates increased in the lorazepam group as compared to the placebo group, suggesting strong non-specific effects. However, the changes in performance in the lorazepam group are not homogeneous across conditions, suggesting that lorazepam also induces specific effects that modulate the integration/segmentation balance. Additional experiments performed with visible apertures or visible diamond vertices indicate that the effects of lorazepam are unlikely to reflect a deficit of motion processing or motion integration mechanisms since performance is only slightly impaired in the lorazepam as compared to the placebo group under these conditions. These results suggest that lorazepam might specifically modulate the saliency of line-ends, presumably because processing these features involves inhibitory mechanisms using GABA as a neuromediator, and in turn modify the balance between motion integration and segmentation.  (+info)

Modification of the pharmacokinetics of high-dose cyclophosphamide and cisplatin by antiemetics. (5/211)

Interpatient variability in exposure to certain chemotherapy agents can influence patient outcome, particularly with high-dose chemotherapy. We evaluated the possibility of a pharmacokinetic (PK) drug-drug interaction between the antiemetic agents and high-dose cyclophosphamide, cisplatin and BCNU (CPA/cDDP/BCNU). Twenty-three self-selected patients treated with high-dose CPA/cDDP/BCNU followed by autologous hematopoietic progenitor cell support (AHPCS) received ondansetron, lorazepam and diphenhydramine as antiemetics. PK parameters for each chemotherapeutic drug in the regimen were compared with those of 129 patients who received exactly the same chemotherapy but an antiemetic regimen substituting prochlorperazine for ondansetron. In addition, we performed a review of the English literature for reported drug-drug interactions between antiemetics and chemotherapy agents that led to modifications in any PK parameters of the chemotherapy agent. Our retrospective study showed that the mean area under the curve (AUC) for both cyclophosphamide (76,600 vs 90,600 microg/ml/min, P=0.001) and cisplatin (525 vs 648 microg/ml/min, P = 0.01) were significantly lower in the ondansetron group when compared with the prochlorperazine group. The AUC for BCNU was not significantly different in both groups (544 vs 677, P = 0.43). We found only one report of modifications of the PK parameters of high-dose chemotherapy agents due to drug-drug interactions with the most commonly used antiemetics in a review of the English literature between 1966 and 1995. We concluded that the AUC of high-dose cyclophosphamide and cisplatin are significantly lower when ondansetron, as opposed to prochlorperazine, is used as the antiemetic. The small sample size and heterogeneity of this group of patients precludes any outcome analysis of pharmacodynamic endpoints such as toxicity or antitumor effect. Nevertheless, the potential for interactions between antiemetics and chemotherapy agents should be taken into account when using different high-dose chemotherapy regimens.  (+info)

Safety and efficacy of a continuous infusion, patient controlled anti-emetic pump to facilitate outpatient administration of high-dose chemotherapy. (6/211)

We evaluated the combination of diphenhydramine, lorazepam, and dexamethasone delivered as a continuous i.v. infusion via an ambulatory infusion pump with patient-activated intermittent dosing (BAD pump) for prevention of acute and delayed nausea/vomiting in patients receiving high-dose chemotherapy (HDC) for peripheral blood progenitor cell (PBPC) mobilization (MOB) or prior to autologous PBPC rescue. The BAD pump was titrated to patient response and tolerance, and continued until the patient could tolerate oral anti-emetics. Forty-four patients utilized the BAD pump during 66 chemotherapy courses, 34 (52%) for MOB and 32 (48%) for HDC with autologous PBPC rescue. The median number of days on the BAD pump during MOB and HDC was 3 (1-6) and 9 (2-19) days, respectively. Complete overall or complete emesis control occurred on 94% of MOB and 89% of HDC treatment days during chemotherapy administration and 72% and 43%, respectively, following chemotherapy administration. Eighty-three percent of MOB and 55% of HDC treatment days were associated with no nausea. While on the BAD pump, no patient experienced severe toxicity or required hospitalization for management of nausea/vomiting. The BAD pump was safe and effective in minimizing nausea and vomiting associated with HDC, and thus, eliminated the need for hospitalization for management of chemotherapy-induced nausea and vomiting.  (+info)

Outpatient detoxification of the addicted or alcoholic patient. (7/211)

Outpatient detoxification of patients with alcohol or other drug addiction is being increasingly undertaken. This type of management is appropriate for patients in stage I or stage II of withdrawal who have no significant comorbid conditions and have a support person willing to monitor their progress. Adequate dosages of appropriate substitute medications are important for successful detoxification. In addition, comorbid psychiatric, personality and medical disorders must be managed, and social and environmental concerns need to be addressed. By providing supportive, nonjudgmental, yet assertive care, the family physician can facilitate the best possible chance for a patient's successful recovery.  (+info)

Effect of potential confounding factors on the thrombolysis in myocardial infarction (TIMI) trial frame count and its reproducibility. (8/211)

BACKGROUND: The potential factors that introduce variability into TIMI frame count (TFC) have not been systematically investigated. The goal of this study was to determine if nitrate use, dye injection rate, catheter size, the phase of the cardiac cycle in which dye is injected, or heart rate affect the TFC and to investigate the reproducibility of the TFC. METHODS AND RESULTS: The dye injection rate was increased 1 mL/s, and angiography was repeated. A coronary angiogram was taken first with an 8F catheter and then with a 6F catheter. After taking angiograms, intracoronary nitrate was given to the patient, and the second angiography was performed. Basal heart rate was increased 20 beats/min, and angiography was repeated. Dye injection was performed at the beginning of systole and diastole. The TFC was not significantly changed by increasing the dye injection rate (P=0.467) or by changing catheter size (P=0.693). Nitrate administration significantly increased the TFC from 26.4+/-11.9 to 32.8+/-13.3 frames (P<0.001). Dye injection at the beginning of diastole significantly decreased the TFC from 30.1+/-8.8 to 24.4+/-7.9 frames (P<0.001) for the left coronary artery and from 24.16+/-4.49 to 21. 24+/-4.45 frames (P<0.001) for the right coronary artery. Increasing heart rate significantly decreased the TFC from 30.4+/-6.1 to 25. 3+/-7.2 frames (P<0.001). Intraobserver and interobserver reproducibility of the TFC was good (mean difference, 1.33+/-1.24 and 2.57+/-1.72 frames, respectively). CONCLUSIONS: Nitrate use, heart rate, and the phase of the cardiac cycle in which dye is injected had significant effects on the TFC. Therefore, studies comparing TFC need to consider these factors, and the use of nitrates should be either standardized or randomized.  (+info)