Effects of a specific benzodiazepine antagonist (RO 15-1788) on cerebral blood flow

RO 15-1788, a specific benzodiazepine antagonist, although it effectively antagonizes the clinical effects of benzodiazepines (i.e., sedation and amnesia), can also induce subjective agonist effects such as sedation or inverse agonist effects such as anxiety. The purpose of this study was to investigate in seven healthy volunteers the effect of RO 15-1788 on cerebral blood flow when intravenously injected alone or with midazolam and to compare its effects with midazolam administered alone. Cerebral blood flow was measured with the 133xenon inhalation technique and the drugs were administered simultaneously in a double-blind, randomized fashion during the four following sessions: placebo-placebo; midazolam-placebo; RO 15-1788-placebo; midazolam-RO 15-1788. No difference in cerebral blood flow was noted between the placebo-placebo, the RO 15-1788-placebo, and the RO 15-1788-midazolam sessions--although midazolam injected alone decreased cerebral blood flow by 30%. The sedation, amnesia, and the electroencephalograph (EEG) and muscle tone changes observed with midazolam-placebo were not present during the RO 15-1788-placebo and RO 15-1788-midazolam sessions. This study demonstrates the absence of effects of RO 15-1788 on cerebral blood flow when injected alone and the efficacy of this new drug in antagonizing the depressant effects of midazolam on cerebral hemodynamics.     

Computed tomography of complications caused by manufacturing defects in synthetic grafts

Two unusual cases of delayed synthetic graft complications resulting from manufacturing defects of knitted Dacron are presented. Computed tomography appears to be a suitable noninvasive alternative examination to angiography in this condition.     

Locus ceruleus lesions and eosinophilic inclusions in MPTP-treated monkeys

Systemic administration of the recently discovered neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces severe clinical parkinsonism and degeneration of the substantia nigra in humans and monkeys. In previous studies, no convincing structural damage to nerve cells outside the substantia nigra could be demonstrated in subhuman primates. Using a protracted MPTP regimen and older animals, we now report locus ceruleus lesions and eosinophilic inclusion bodies in squirrel monkeys. The inclusions were seen only in areas where Lewy bodies are found in human Parkinson's disease. No such abnormalities were seen in control animals. These findings suggest that similarities between the neuropathology of MPTP-induced parkinsonism in the monkey and human Parkinson's disease are greater than first thought and increase the usefulness of the MPTP monkey model for research in Parkinson's disease.     

In Vitro Growth of Thymic Tumor Cell Lines from Xenopus

A spontaneous lymphoid thymus tumor was discovered in a male Xenopus of the MHC ff genotype. The tumor cell can be transplanted in histocompatible larval ff hosts, but not in ff adults unless irradiated (3000 rad). The tumor is rejected by allogeneic hosts. The tumor cells express neither markers of the B-cell lineage nor MHC encoded molecules; they express only markers of the T-cell lineage. Its lymphoid population is clonal as revealed by the existence of a stable rearrangement pattern of the immunoglobulin genes. Cell lines growing continuously in vitro have been derived from the tumor.     

Multiple digital fractures from automobile air bag inflation

Automobile air bag inflation-caused injuries to the chest, neck, and face, in particular the orbital contents, are infrequent but recognized. We report the occurrence of multiple digital fractures in the left hand of a 30-yearold male driver as a result of sudden air bag inflation. Continued monitoring of the potential hazards of this device is suggested.     

Estimated daily energy expenditure and blood lipids in adolescents: the Québec Family Study.

PURPOSE: To examine the association between estimated daily energy expenditure and blood lipids in a sample of adolescents. METHODS: The sample consisted of 415 males and 356 females aged 10-19 years, mainly French Canadian, recruited from the greater Quebec City area through the media as part of Phase I of the Quebec Family Study. Estimates of daily energy expenditure (DEE) were obtained with a 3-day physical activity record. Blood lipids were measured by standard procedures. The sample was stratified into three activity groups (least active, less than 25th percentile of DEE; moderately active, 25-74th percentile of DEE; and most active, 75th percentile or greater of DEE), and also by clinical cutpoints for blood lipids. Analysis of covariance, controlling for age and fatness, was conducted to compare blood lipids within gender across activity groups. Logistic regression analysis, controlling for age and fatness, was used to estimate the relative risk of being classified with an undesirable level of a blood lipid parameter on the basis of the DEE. RESULTS: Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were not significantly different across activity groups in males or females. High-density lipoprotein cholesterol (HDL-C) was significantly different across activity groups in males (p <.05) and females (p <.05), but the pattern of variation was different between genders. In males, the TC/HDL-C and LDL-C/HDL-C ratios decreased between the moderately active and most active groups (p <.05). Significant differences remained when subcutaneous fatness was considered as a covariate. The results from logistic regression analysis indicated that the odds ratios for low HDL-C levels was significant only in low DEE girls (odds ratio 2.83) compared with high DEE girls. CONCLUSIONS: The results suggest that increased energy expenditure and physical activity are associated with higher levels of HDL-C in adolescents of both sexes.     

Diffusion of piperacillin in the eye]

Intraocular diffusion of piperacillin was studied in 42 patients scheduled for cataract surgery (n = 35) or vitrectomy (n = 7). Piperacillin was administered intravenously (4 g/injection). Thirty-four patients were given a single dose and 8 were given two doses 12 hours apart. Peak piperacillin levels in the aqueous (7.3 mg/l) occurred one hour after the injection; levels in the vitreous were low (less than 0.6 mg/l). Intraocular diffusion of piperacillin was also studied in rabbits with an experimental Staphylococcus epidermidis infection of one eye; the other eye served as the control. In pigmented rabbits (6 Fauve de Bourgogne animals), increased diffusion and decreased elimination of piperacillin were seen in the aqueous, iris and cornea of the infected eyes, as compared with uninfected control eyes. In albino rabbits (6 New Zealand animals), results were less conclusive, with a difference between the infected and healthy eyes appearing only during the second hour following the injection. The good diffusion of piperacillin in the aqueous, especially in infected eyes (at least in rabbits), suggests that this drug may be useful for the treatment of ocular infections provided it is initiated early and given in combination with another antimicrobial exhibiting good intraocular diffusion.     

A novel pancreatic endocrine tumor suppressor gene locus on chromosome 3p with clinical prognostic implications.

The molecular pathogenesis of pancreatic endocrine tumors is largely unknown. Such tumors are more likely to develop in individuals with the von Hippel-Lindau (VHL) syndrome. We sought to determine whether allelic loss of the recently identified VHL tumor suppressor gene on chromosome 3p25-26 occurs in the more common sporadic forms of these tumors. Allelic loss on chromosome 3p was identified in 33% of 43 patients with endocrine tumors of the pancreas. The smallest common region of allelic loss, however, centered not at the VHL locus, but rather at 3p25, centromeric to VHL. Furthermore, no mutations of the VHL gene were identified in these tumors. Loss of alleles on chromosome 3p was associated with clinically malignant disease, whereas tumors with retained 3p alleles were more likely to be benign. Thus, the VHL gene does not appear to play a pathogenic role in the development of sporadic pancreatic endocrine tumors. Instead, a locus at chromosome 3p25 may harbor a novel pancreatic endocrine tumor suppressor gene, and allelic loss of this chromosomal region may serve as a molecular marker that helps distinguish benign from clinically malignant disease.     

A multicenter clinical trial of gadolite oral suspension as a contrast agent for MRI

The purpose of this study was to assess the effectiveness and safety of Gadolite Oral Suspension as a gastrointestinal (GI) contrast agent for MRI in a phase II and two phase III multicenter clinical trials. Gadolite was administered to 306 patients with known or suspected abdominal and/or pelvic disease. MRI with T1- and T2-weighted sequences was performed before and after ingestion. Efficacy was evaluated by having two masked readers rate the certainty of their MR diagnosis (0 = uncertain, 1 = probable, 2 = definite) on randomly presented pre- and post-Gadolite Oral Suspension enhanced images. Principal investigators also evaluated the images and established the final diagnosis. Vital signs, clinical chemistries, and adverse events were documented. Blood and urine samples were analyzed for gadolinium content to determine whether Gadolite Oral Suspension was absorbed systemically. Certainty in MR diagnosis increased significantly (P < .001) for both blinded readers between pre- and post-Gadolite images (.49–1.18 for reader 1; .46–1.53 for reader 2). Sensitivity, specificity, and accuracy also increased for both masked readers. No gadolinium was detected in blood or urine samples. There were no serious adverse events and no apparent drug-related trends in mean vital signs or laboratory values. Gadolite is a highly effective, safe, and well tolerated contrast agent for clinical use with MRI.