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Biomedical subjects

A Davis

Publications and source records attributed to A Davis.

At least 325 records · Page 18Linked to original sources

Amoebiasis and its control.

On a global scale, 480 million people were recently estimated to be infected with Entamoeba histolytica and some 48 million people suffer from invasive amoebiasis. The latter, in the intestinal and extra-intestinal forms, accounts for 40 000 to 110 000 deaths annually. In view of this considerable mortality and morbidity, more research is urgently needed so that more effective control strategies may be introduced.This Update article reviews the magnitude of the problem, clinical and laboratory diagnosis, present treatment and prevention measures, possible control strategies, and research priorities.

Amebiasis↗

Use of the EEA stapling device in anastomoses of the small intestine.

A technical modification is described for introducing the EEA stapler into the small intestinal lumen for anastomosis without creating an additional enterotomy. This method, which permits a more rapid formation of anastomoses, has been used to form Roux-en-Y jejunojejunostomies without extensive complications in six patients. Such a technique may have particular application when multiple anastomoses are contemplated in fragile patients with chronic disease.

Humans↗

Bacterial meningitis in Johannesburg--1980-1982.

A 2-year retrospective study of aetiology, age distribution, seasonal variation and antimicrobial sensitivity patterns of bacteria isolated from patients with meningitis in five Johannesburg hospitals for White, Black, Coloured and Asian patients was performed. Neisseria meningitidis was isolated most frequently, followed by Streptococcus pneumoniae, Haemophilus influenzae, Escherichia coli and Streptococcus group B. In the Black population 73% of the meningococcal infections occurred in patients over 3 years of age, and the majority of these infections were caused by serogroup A organisms. Virtually all (93%) of the H. influenzae infections occurred in children of less than 3 years of age. Of the isolates tested, 16% of the meningococci, 4,5% of the H. influenzae and 47% of the pneumococci were resistant to sulphadiazine, ampicillin and penicillin respectively.

Adolescent↗

Reconstitution of [3H]3-cyanoimipramine ([3H]Ro 11-2465) sites solubilised from human platelets.

[3H]3-Cyanoimipramine has been characterised as a pseudoirreversible ligand at imipramine binding sites making it useful for molecular characterisation studies. Using this ligand, I now report that it is possible to solubilise the binding site molecule with cholate. Gel permeation chromatography on a Sepharose 4B column equilibrated in 0.1% cholate revealed a micellar size of 4.1 nm. Subsequent removal of cholate (from an initial concentration of 2% to less than 0.02%) in the presence of Azolectin (soybean lipid extract) led to reconstituted material that could be retained on glass fibre filters. Electron microscopy revealed apparent micelles of approximately 1 micron diameter. Over 16% of the original, membrane-bound, binding sites were recovered in the reconstituted material along with a similar percentage of the protein. This reconstituted material was moderately stable for up to 3 days after its preparation.

Binding Sites↗

Temperature-sensitive conformational changes in [3H]imipramine binding sites and the involvement of sulphur-containing bonds.

Recently, a reversible, temperature-sensitive conformational change has been observed which alters [3H]imipramine binding parameters. I now report that the conformational change probably occurs within the binding site protein and is not due to allosteric interactions or altered ligand kinetics. Evidence comes from the identification of sulphur-containing bonds in the binding site molecule which are differentially exposed at different incubation temperatures. Binding of [3H]imipramine to outdated human platelets is maximal at 4 degrees C; when the incubation temperature is raised to 23 degrees C, a loss of affinity is observed. N-Ethylmaleimide, an alkylator of sulphydryl groups, could completely inhibit the binding at both temperatures but did so much faster at 23 degrees C than at 4 degrees C. Dithioerythritol (DTE) and beta-mercaptoethanol reduce disulphide bonds and were found to enhance [3H]imipramine binding. Again, these reagents were more potent at 23 degrees C than at 4 degrees C. None of these reagents caused these effects by interacting with the ligand. Simultaneous preincubation with excess fluoxetine could prevent the action of DTE on specific [3H]imipramine binding. It is concluded that sulphur-containing bonds are close to, or located at the [3H]imipramine binding site, and their conformation is sensitive to changing temperatures.

Blood Platelets↗

Life change and onset of cancer in identical twins.

The relationship of life change to the onset of cancer was studied in 22 pairs of HLA-identical siblings who were discordant for hematologic malignancies. The twin pairs were hospitalized for bone marrow transplantation. Life change was measured using a well-validated instrument, the Schedule of Recent Experiences (SRE). Contrary to our expectations, we were unable to document increased life changes in the sick twins. The timing of administration of the SRE with respect to the transplant did influence reporting of life events. However, regardless of timing of administration, in the period antedating the diagnosis of malignancy the healthy donor twins had increased or equivalent life changes when compared to their sick twins.

Adolescent↗

Detecting hearing-impairment in neonates--the statistical decision criterion for the Auditory Response Cradle.

The Auditory Response Cradle (ARC) has great potential for detecting severe hearing impairments in neonates. This article reviews the ARC's statistical decision algorithm and presents data that show its present efficiency is below the proposed criterion (Bennett and Wade, 1980) in a high proportion of cases. Two alternative decision rules are proposed for use in screening neonates with the ARC. The first uses a test of fixed length and the second uses a statistically more controlled method based on the sequential probability ratio test of Wald.

Audiometry↗

The effects of bilateral renal transplantation on pelvic hemodynamics and sexual function.

Sexual function and internal iliac artery (IIA) patency were determined in 24 patients who had received at least two renal transplants, one in each iliac fossa, at the University of Maryland and Johns Hopkins Hospitals from 1975 to 1979. The pelvic hemodynamics of each patient were assessed with a penile/brachial blood pressure index (PBI). The rate of sexual dysfunction, as determined by questionnaires and personal interviews, was 46% (11 of 24 patients) compared with only 21% (five of 24 patients) after a single transplant. Nine of the 11 patients who were impotent had bilateral IIA occlusion and four of these nine had a PBI less than 0.70. One of the four patients regained full sexual function after a revascularization procedure, which confirmed that this impotence had a vascular etiology. Results of this study show that vascular insufficiency, but not necessarily vasculogenic impotence, was present in at least four of the 11 patients who were impotent (36%) and may have been avoidable by sparing at least one IIA during renal transplant procedures.

Adult↗

Minimal requirements for planning control projects.

The different life cycles of trematodes causing the snail-transmitted infections, the complex interactions of the numerous groups of variables representing the five major areas of the epidemiology - human prevalence, incidence and intensity rates, parasite strains, intermediate hosts, ecological backgrounds and human behavioural factors - all combine to render control projects both area and parasite specific. Control must never be equated with eradication which is the complete and permanent cessation of transmission - and rarely, if ever, achievable. In medical and epidemiological terms, control means reduction of morbidity and mortality. Minimum requirements common to efficient planning for any control projects are: a community awareness of the problem; a community expression for the need of control; pathological, statistical and socio-economic evidence of morbidity/mortality produced and the associated economic loss to area, region or country, medical interest and governmental commitment to action as a priority in health policies; appropriate, simple, yet adequate diagnostic technology; appropriate control tools, which, for this group of infections, will rely heavily on population-based chemotherapy; a cadre of trained technicians, field workers and health educators; a programme for training trainers; a delivery system which can be used as an entry point to other health improvements, e.g. sanitation, nutrition, family planning; baseline demographic and epidemiologic information, a pre-tested system of data recording, collection, reduction and analysis; and, finally, funding support. These factors will be discussed.

Anthelmintics↗

Kinetic properties of [3H]2-nitroimipramine binding to human platelets.

2-Nitroimipramine has previously been reported to be a slowly dissociating ligand at [3H]imipramine binding sites in rat brain. This binding site has been tentatively identified as the recognition site for the serotonin transport mechanism. Since we have previously solubilized imipramine binding sites from platelets, the slowly dissociating nature of this compound was of interest in the continuance of our molecular characterisation studies. Association of [3H]2-nitroimipramine to human platelets was complete within 2 h and saturation analyses implied that the affinity of this ligand was similar to that of [3H]imipramine. Moreover, the ligand binding was inhibited by non-radioactive compounds in a manner consistent with reversible, competitive kinetics. However the dissociation rate, after only 20 min association, was slow (t1/2 = 8.3 h) as compared with [3H]imipramine. After prolonged incubation with membranes (16-20 h) the dissociation rate for [3H]imipramine was essentially unaltered whereas that for [3H]2-nitroimipramine decreased approximately three fold. I conclude that [3H]2-nitroimipramine gradually becomes more slowly reversible upon prolonged incubation, but following short incubation periods it behaves essentially like [3H]imipramine.

Blood Platelets↗

Temperature-sensitive reversible loss of [3H]imipramine binding sites: evidence suggesting different conformational states.

Previous studies have indicated that the tertiary tricyclic antidepressant imipramine binds with high affinity to a site related to the serotonin uptake mechanism. We have further characterized this site with regards to the effects of temperature, pH and calcium ions on both rat cerebral cortex homogenates and outdated human platelets. The binding of [3H]imipramine to these sites is maximal at 4 degrees C. When the assay temperature is increased to 23 degrees C, there is approximately a 50% decrease in the maximal number of binding sites (Bmax) with no apparent change in the affinity for the ligand. On further raising the temperature to 37 degrees C there is no further decrease in Bmax but there is an increase in the dissociation constant (KD). These temperature related changes are reversed when the assay temperature is again lowered to 4 degrees C. Decreasing the pH of the incubation mixture from 7.5 to 7 (which is the pH change also observed upon changing the temperature of the incubation mixture from 4 to 37 degrees C) decreased [3H]imipramine binding by 10-20%, an amount which does not account for the changes observed. Similarly, neither calcium nor EDTA altered these reversible changes. Irreversible loss of binding sites was observed on prolonged incubation at 23 or 37 degrees C. After 20 h preincubation at 23 or 37 degrees C, 15 or 30% of the binding respectively could not be restored by lowering the temperature to 4 degrees C. This permanent loss was enhanced by calcium and inhibited by EDTA. These results suggest that reversible conformational changes in the [3H]imipramine binding site can be observed.

Animals↗

Temperature-sensitive conformational changes in membrane-bound and solubilized [3H]imipramine binding sites.

[3H]Imipramine binding sites are located on serotonergic nerve terminals and on blood platelets. Previous studies on our laboratories have indicated temperature-sensitive conformational changes in [3H]imipramine binding sites in hippocampal and cerebral cortex membranes. We now report that similar changes are observed in both membrane-bound and digitonin-solubilized [3H]imipramine binding sites of human blood platelets. This may indicate integrity of the solubilized binding site.

Animals↗

Solubilization and assay of [3H]imipramine binding sites from human platelets.

[3H]Imipramine binding sites were characterized on outdated (72-96 h) human platelets. The binding site profile was very similar to that previously described for fresh platelets and for CNS membrane preparations. [3H]Imipramine binding sites are believed to represent the recognition site for the 5-hydroxytryptamine uptake system. In order to further investigate this molecular relationship, we solubilized [3H]imipramine binding sites using 1% digitonin and characterised them using a polyethylene glycol precipitation assay. Solubilization did not alter the pharmacological specificity or affinity of the [3H]imipramine binding site and recovery of sites was very high. It was concluded that the solubilization procedure left the binding site remarkably intact. The ready availability of platelets and the convenience of the binding assay makes this system amenable for further purification steps.

Binding Sites↗

Experiences with phrenic nerve pacing in children.

We report a series of four spinal cord-injured children with ventilator dependency who were implanted with radiofrequency phrenic nerve pacers. At injury, their ages ranged from 6 to 9 years. Implantation occurred from 15 to 47 months following injury. The longest term of pacing has been 59 months. One patient, who was being paced full-time, died suddenly at 32 months of a viral myocarditis. Two patients underwent bipolar phrenic implantation in the neck, while two other patients underwent bilateral thoracotomy with monopolar electrode implantation in the mediastinum. There have been no complications related to pacer dysfunction in the postoperative course. Selective pacing schedules have been developed to minimize problems related with external mechanical ventilation. Radiofrequency phrenic nerve pacing is of value in the complete rehabilitative management of these severely disabled children.

Adult↗