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Biomedical subjects

M W Brown

Publications and source records attributed to M W Brown.

At least 109 records · Page 6Linked to original sources

A comparison of the sequestration of cadmium and zinc in the tissues of rainbow trout (Salmo gairdneri) following exposure to the metals singly or in combination.

Rainbow trout were exposed to either cadmium (9 micrograms/l) or zinc (100 micrograms/l) in their aquarium water. They were then transferred to water containing concentrations of cadmium (54 micrograms/l) that would have otherwise proved fatal to the majority of the fish without the pretreatment. Most of the fish survived under both sets of conditions. However, two different mechanisms seem to be involved in the protection of the animals against the toxic manifestations of cadmium. In both cases, more than 99% of the total body load of cadmium was found in the liver, kidney and gills of the animals. Analysis of the metal-binding proteins in these organs was carried out. In the fish exposed to the two concentrations of cadmium, the toxic metal was found only in association with two low mol. wt specific binding proteins despite the presence of zinc- (and copper)-containing isometallothioneins in all three organs. On the other hand, cadmium was distributed between these binding-proteins and metallothioneins in the liver, kidney and gill of the trout pretreated with zinc before their exposure to cadmium.

Animals↗

Lumbosacral plexus stretch injury following the use of the modified lithotomy position.

The modified lithotomy position is used to provide simultaneous operative exposure to the abdomen and perineum. We report 3 lumbosacral plexus complications following use of this position. A mechanism involving stretch secondary to hyperabduction seems most likely. Electromyography is helpful in the diagnosis and the prognosis seems to be good.

Adolescent↗

Effect of ketoconazole on hepatic oxidative drug metabolism.

Several clinical reports have suggested (but not demonstrated) that ketoconazole, a broad-spectrum antifungal drug, may inhibit hepatic oxidative drug metabolism in man. We recently demonstrated that ketoconazole inhibits caffeine and aminopyrine oxidation in the rat; we now study the influence of ketoconazole on theophylline and chlordiazepoxide kinetics in man. These studies were performed before and after varying doses of ketoconazole within the currently accepted therapeutic range. Ketoconazole had no effect on theophylline clearance, whereas the drug impaired chlordiazepoxide clearance from plasma. After a single dose of ketoconazole, there was a 20% decrease in clearance and a 26% decrease in volume of distribution without evidence of inhibition of drug metabolism. These changes apparently were not related to ketoconazole dose. After repetitive dosing with ketoconazole, chlordiazepoxide clearance decreased by 38% and was associated with reduced concentrations of its first oxidative metabolite, N-desmethylchlordiazepoxide. We conclude that ketoconazole inhibits at least one subset of the hepatic mixed-function oxidase system, but is not as general an inhibitor of hepatic oxidative drug metabolism as cimetidine appears to be. For some coadministered drugs, ketoconazole may also have an effect on other kinetic parameters such as volume of distribution. Therefore, we caution that clinically important drug interactions may occur with the concurrent use of ketoconazole.

Adult↗

A note on the contamination of eye-drops following use by hospital out-patients.

Examination of 273 eye-drops, returned to a hospital pharmacy by out-patients showed that 27% were contaminated. Common contaminants included Bacillus spp, Staphylococcus albus and Sarcina spp. Those eye-drops containing the preservatives chlorbutol or thiomersal showed above average levels of contamination, thus questioning the suitability of these preservatives for ophthalmic preparations.

Bacteria↗

The distribution of Timm's stain in the nonsulphide-perfused human hippocampal formation.

A detailed description is given of the distribution of Timm's staining in the human hippocampal formation. In sections cut transverse to the long axis of the hippocampal formation the same pattern of staining is seen throughout almost all of the structure, i.e., through all the main body except the most caudal region and, following the medial bend made by the long axis, through most of the pes hippocampi. The staining typically filled almost the whole of the hilus of the dentate gyrus and the whole depth of the adjacent stratum pyramidale and stratum lucidum of subfield CA3. Rostrally, staining was traced into the tip of the uncus. Caudally, staining was traced to the inferior surface of the splenium at the apex of the caudal taper of the hippocampus. No staining was found in the gyrus fasciolaris, indusium griseum, or anterior hippocampal rudiment. Except in the medial part of the pes hippocampi, the Timm's staining did not reach the proximal border of the subfield CA1. In some sections of the main body of the hippocampus a narrow, infragranular stain-free zone was observed in the hilus. In the dentate gyrus of three older subjects, but not in those of three younger subjects, supragranular staining was found. It is argued that the Timm's staining described in this study is specific to the hippocampal mossy fibres. The distribution of the staining is discussed in relation to the boundaries of subfields CA3 and CA2 as delineated by other authors.

Aged↗

Modifiability of responsiveness in a visual projection area of the chick brain: visual experience is only one of several factors involved.

The effects of visual experience on neuronal responsiveness in the hyperstriatum accessorium, a visual projection area, were investigated in 4 groups of domestic chicks, each comprising dark-reared (total = 44) and visually experienced (total = 34) birds. Visually experienced birds were placed singly in running wheels facing a flashing red light for 3 h; wheel revolutions were used as a measure of the chicks' locomotor activity. At approximately equal to 48 h after hatching each chick was anaesthetized and a microelectrode advanced in 250 micron steps through the left Wulst. After each step the responsiveness of units to diffuse retinal illumination (light flashes) was tested. Each recording site at which responses greater than or equal to 5 successive flashes could be evoked was classified as a response site. In some chicks at least one site responding briskly to greater than or equal to 15 successive flashes was found deep to the hyperstriatum accessorium. The zone of markedly increased responsiveness is referred to as the visually responsive lamina. The effect of visual experience on the response of units in the hyperstriatum accessorium varied between the groups of chicks. Visual experience did not significantly effect neuronal responsiveness in this region for chicks without a visually responsive lamina. For chicks with a lamina there was an effect of visual experience, but the effect again varied between groups. When data from inactive, visually experienced chicks were excluded, the group-to-group variation ceased to be significant. Thus visual experience alone was not adequate consistently to bring about long-term changes in the responsiveness of neurones in the hyperstriatum accessorium. Such experience was likely to increase neuronal responsiveness provided the chicks: were behaviourally active; and possessed a visually responsive lamina.

Animals↗

Suboptimal results in full thickness skin graft urethroplasty using an extrapenile skin donor site.

We performed 22 full thickness skin graft urethroplasties for treatment of urethral stricture disease or hypospadias. Excellent results were achieved in 18 cases in which a penile skin donor site was used. Three failures occurred in 4 cases in which the full thickness graft was raised from the inner aspect of the upper arm. These results suggest caution when extrapenile skin is used for such repairs.

Humans↗

Initial experiences with percutaneous and transurethral ablation of postoperative ureteral strictures in children.

A transurethral or percutaneous procedure was used in 11 children and 1 young adult in an attempt to correct obstruction at the site of previous pyeloplasty, ureteroenterostomy or vesicoureteral reimplantation into the bladder. When a guide wire could be passed through the obstructed segment a balloon would always pass over the wire. The balloon could then be inflated to dilate the narrowed area. Five patients in whom the obstruction was detected and treated in this manner within a few months after the initial operation exhibited relief of obstruction and these good results have persisted. The exception to this generalization is a 5-year-old girl who did not experience durable improvement in obstruction when treated 3 months after ureteral implantation. Four additional children with ureteral strictures diagnosed 1 to 4 years postoperatively also were not improved by dilation, even when a post-dilation stent (usually a double-J catheter) was used for 6 to 8 weeks. Two boys with recurrent ureteropelvic junction obstruction after pyeloplasty underwent percutaneous resection of the ureteropelvic junction. In 1 boy the hook electrode and cautery were used and stenosis recurred, apparently due to thermal injury. In the other boy a sharpened hook electrode was used to incise the ureteropelvic junction, which has stayed open for 18 months, and he is our longest followup.

Adult↗

Cellular defense in critically ill surgical patients.

Cell-mediated immunity was examined using 4 recall antigens in 102 critically ill surgical patients treated in an ICU. There were 4 (14%) deaths in 28 patients with positive reactions (R), compared to 33 (45%) deaths in 74 nonreactors (NR) (p less than .01). Thirty-seven of the patients were admitted after trauma, and mortality in this group was not significantly different between R and NR patients. Repeat testing in 40 NR patients who remained in the ICU for more than 7 days showed that 30 remained NR (70% mortality) and 10 became R (20% mortality, p less than .001). Peripheral blood lymphocytes from the patients showed a reduced response to concanavalin A, but a normal response to phytohemagglutinin and pokeweed mitogen. Mononuclear cells and granulocytes both showed a small increase in chemotactic response to casein, suggesting that the reduced response to skin testing may be partly due to defective T-cell function, rather than impaired phagocyte chemotaxis.

Adolescent↗

Chemotherapy of squamous cell cancer of the head and neck.

Forty patients with advanced squamous cell cancer of the head and neck were treated with methotrexate, cisplatin, and bleomycin. Major regression of disease occurred in 69%; 30% of patients achieved complete remission. Fifteen patients received chemotherapy as the initial treatment, followed by either radiotherapy or surgery or both. Subsequent therapy was not prejudiced by this approach. The results demonstrate the marked sensitivity of these tumors to these three agents, and the need for further assessment of their use in optimal patient care.

Adolescent↗

Effects of lorazepam on rate of forgetting, on retrieval from semantic memory and on manual dexterity.

Using a double-blind procedure, 16 out of 32 volunteer subjects (students) each took 2.5 mg of lorazepam (Ativan) orally and the remainder took a placebo. To overcome the problem of wide variation in individual tolerance to the drug, impairment on a task unrelated to memory (a manual dexterity task) was used to divide drug subjects into a group appreciably affected by the drug, subgroup 1, and a group minimally affected, subgroup 2. Only subgroup 1 showed consistent impairment of episodic memory. Both subgroups showed some impairment in a semantic memory task (generation of words from a specified category), but this was confined to the rate at which the task was carried out. The main aim of the experiment was to examine the effect of lorazepam on the rate of forgetting of word lists when drug and control subjects' initial recall levels were equalized. There was no evidence that the drug affected rate of forgetting: this suggests that it does not affect retention. There was also no evidence that it affected retrieval, since there was no impairment in the recall of material presented before administration of the drug. Hence its locus of action is attributed to input, specifically to impaired encoding of contextual information.

Adult↗

Amnesia-producing drugs affect hippocampal frequency potentiation.

The effects of intravenous injections of lorazepam, scopolamine and propranolol upon hippocampal potentiation produced by commissural stimulation have been investigated in rats anaesthetized with urethane. Administration of 250 micrograms/kg or 500 micrograms/kg lorazepam significantly delayed the onset of secondary potentiation (frequency potentiation) of the population spikes recorded in subfields CA1 and CA3 of the dorsal hippocampus. Scopolamine also delayed the onset of frequency potentiation in CA1, but only at high dose (10 mg/kg). No other measured parameters of frequency potentiation, paired-pulse potentiation or post-tetanic potentiation were affected by any of the drugs. Lorazepam (greater than or equal to 250 micrograms/kg) and propranolol (3 mg/kg) reduced the severity of hippocampal after-discharge. Rhythmic entrainment of after-discharges was occasionally observed. The results are discussed in relation to the possible link between hippocampal potentiation and memory processes.

Amnesia↗

Multicentric glioma as a cause of multiple cerebral lesions.

Two new cases of multicentric glioblastoma are presented to re-emphasize the needs (a) to consider this diagnosis in patients with multiple intracerebral lesions suggesting metastases or abscesses and (b) to consider prompt biopsy of accessible lesions in these patients.

Brain↗