The affinities, potencies and efficacies of some benzodiazepine-receptor agonists, antagonists and inverse-agonists at rat hippocampal GABAA-receptors.

The abilities of some benzodiazepine-receptor agonists, antagonists and inverse agonists to modulate the inhibitory potency of the gamma-aminobutyric acid (GABA)A-receptor agonist, isoguvacine, on the CA1 population spike recorded from slices of rat hippocampus, were determined. Concentration-response curves were constructed of the extent to which the benzodiazepine-receptor ligands shifted the isoguvacine concentration-response curve to the left or right. These were compared to their displacement curves of [3H]-Ro15-1788 binding to rat hippocampal membranes under near physiological assay conditions. The above comparisons suggest that the effect on the potency of isoguvacine produced by the benzodiazepine-receptor agonists, diazepam and flunitrazepam, and the partial agonists, Ro16-6028 and Ro17-1812, closely parallels their degree of benzodiazepine-receptor occupancy. Thus, the partial agonists, Ro16-6028 and Ro17-1812, were unable to produce as large a maximum response as the full agonists, diazepam and flunitrazepam. The maximum effects produced by diazepam, flunitrazepam, Ro16-6028, Ro17-1812, the antagonist, propyl-beta-carboline-3-carboxylate, and the inverse agonist, methyl-6, 7-dimethyl-4-ethyl-beta-carboline-3-carboxylate (DMCM), on the potency of isoguvacine in the hippocampal slice corresponded to the change in their affinities produced by the addition of GABA in the radioligand binding studies (GABA-shift). This suggests that the changes in affinity of benzodiazepine-receptor ligands produced by GABAA-receptor activation reflects their ability to modify GABAA-receptor function. The benzodiazepine-receptor antagonists, Ro15-1788 and CGS 8216, had apparent agonist and inverse agonist effects, respectively, on the potency of isoguvacine. These effects occurred at concentrations above those required for saturation of the benzodiazepine-receptor, as labelled by [3H]-Ro15-1788, and were not in agreement with the absence of any effect of GABAA-receptor stimulation in the GABA-shift experiments.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral amyloid angiopathy and spontaneous intracerebral haemorrhage. Report of a sporadic case in a young Chinese.

A 49-year-old Chinese male with spontaneous intracerebral haemorrhage due to cerebral amyloid angiopathy is presented. This is the first case reported in the Chinese population, and the youngest patient described without a family history or associated mental disorder.     

The pathogenicity of coagulase negative staphylococcus in the presence of silicone rubber implants

Coagulase negative staphylococci have long been thought to be harmless skin commensals. However they are now recognised as important pathogens in patients who have undergone insertion of prosthetic devices. We present three patients with infection following the insertion of silicone polymer prostheses, in whom a coagulase negative staphylococcus was the pathogen. All responded to antibiotic treatment. It is important to alert the bacteriologist to the presence of an implanted prosthesis when wound swabs are sent from an area showing clinical signs of infection. The coagulase negative staphylococci may otherwise be regarded falsely as merely skin contaminants.     

Altered cerebral blood flow and glucose metabolism in patients with liver disease and minimal encephalopathy

We measured CBF and the CMRglc in normal controls and in patients with severe liver disease and evidence for minimal hepatic encephalopathy using positron emission tomography. Regions were defined in frontal, temporal, parietal, and visual cortex; the thalamus; the caudate; the cerebellum; and the white matter along with a whole-slice value obtained at the level of the thalamus. There was no difference in whole-slice CBF and CMRglc values. Individual regional values were normalized to the whole-slice value and subjected to a two-way repeated measures analysis of variance. When normalized CBF and CMRglc values for regions were compared between groups, significant differences were demonstrated (F = 5.650, p = 0.00014 and F = 4.58, p = 0.0073, respectively). These pattern differences were due to higher CBF and CMRglc in the cerebellum, thalamus, and caudate in patients and lower values in the cortex. Standardized coefficients extracted from a discriminant function analysis permitted correct group assignment for 95.5% of the CBF studies and for 92.9% of the CMRglc studies. The similarity of the altered pattern of cerebral metabolism and flow in our patients to that seen in rats subjected to portacaval shunts or ammonia infusions suggests that this toxin may alter flow and metabolism and that this, in turn, causes the clinical expression of encephalopathy.     

Digital archive center: implementation for a radiology department.

OBJECTIVE. In this article, we describe the implementation of a digital archive center for a radiology department in a 700-bed teaching hospital. MATERIALS AND METHODS. The archive center consists of two identical archive systems, each comprising five components: an archive server, a data-base server, an optical disk library, a stand-alone optical disk drive, and a communication network. An image management system controls the image traffic from acquisition devices to display stations. A fault-tolerant mechanism was built into the archive center to achieve a 100% uptime. RESULTS. The center has been in operation for over 6 months. We have not experienced a single total system failure during this period. It currently archives all digital images from three MR units and four CT scanners and selected images from three computed radiographic systems and two laser film digitizers. The center archives between 1.5 and 2.0 gigabytes of images per workday. CONCLUSION. With its built-in fault-tolerant mechanism, we believe that the implemented archive center is very reliable and is suitable for a radiology department to archive its digital images.     

Delineating the sites and progression of in vivo atrophy in multiple system atrophy using fluid-registered MRI.

We describe the pattern and progression of atrophy delineated using fluid registration of serial magnetic resonance imaging scans in a case of multiple system atrophy (MSA). The in vivo findings were consistent with those found at postmortem, including significant supratentorial atrophy concurrent with an unusual degree of cognitive impairment for MSA.     

Adult-to-adult living donor liver transplantation using extended right lobe grafts.

OBJECTIVE: The authors report their experience with living donor liver transplantation (LDLT) using extended right lobe grafts for adult patients under high-urgency situations. SUMMARY BACKGROUND DATA: The efficacy of LDLT in the treatment of children has been established. The major limitation of adult-to-adult LDLT is the adequacy of the graft size. A left lobe graft from a relatively small volunteer donor will not meet the metabolic demand of a larger recipient. METHODS: From May 1996 to November 1996, seven LDLTs, using extended right lobe grafts, were performed under high-urgency situations. All recipients were in intensive care units before transplantation with five having acute renal failure, three on mechanical ventilation, and all with hepatic encephalopathy. The median body weight for the donors and recipients was 58 kg (range, 41-84 kg) and 65 kg (range, 53-90 kg), respectively. The body weights of four donors were less than those of the corresponding recipients, and the lowest donor-to-recipient body weight ratio was 0.62:1. The extended right lobe graft was chosen because the left lobe volume was <40% of the ideal liver mass of the recipient. RESULTS: Median blood loss for the donors was 900 mL (range, 700-1600 mL) and hospital stay was 19 days (range, 8-22 days). Homologous blood transfusion was not required. Two donors had complications (one incisional hernia and one bile duct stricture) requiring reoperation after discharge. All were well with normal liver function 5 to 10 months after surgery. The graft weight ranged from 490 g to 1140 g. All grafts showed immediate function with normalization of prothrombin time and recovery of conscious state of the recipients. There was no vascular complication, but six recipients required reoperation. One recipient died of systemic candidiasis 16 days after transplantation and 6 (86%) were alive with the original graft at a median follow-up of 6.5 months (range, 5-10 months). CONCLUSIONS: When performed by a team with experience in hepatectomy and transplantation, LDLT, using an extended right lobe graft, can achieve superior results. The technique extends the success of LDLT from pediatric recipients to adult recipients and opens a new donor pool for adults to receive a timely graft of adequate function.     

Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by L-dopa and ropinirole in the MPTP-lesioned marmoset.

Long-term dopamine replacement therapy of Parkinson's disease leads to the occurrence of dyskinesias. Altered firing patterns of neurons of the internal globus pallidus, involving a pathological synchronization/desynchronization process, may contribute significantly to the genesis of dyskinesia. Levetiracetam, an antiepileptic drug that counteracts neuronal (hyper)synchronization in animal models of epilepsy, was assessed in the MPTP-lesioned marmoset model of Parkinson's disease, after coadministration with (1) levodopa (L-dopa) or (2) ropinirole/L-dopa combination. Oral administration of levetiracetam (13-60 mg/kg) in combination with either L-dopa (12 mg/kg) alone or L-dopa (8 mg/kg)/ropinirole (1.25 mg/kg) treatments was associated with significantly less dyskinesia, in comparison to L-dopa monotherapy during the first hour after administration. Thus, new nondopaminergic treatment strategies targeting normalization of abnormal firing patterns in basal ganglia structures may prove useful as an adjunct to reduce dyskinesia induced by dopamine replacement therapy without affecting its antiparkinsonian action.