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Biomedical subjects

A Davis

Publications and source records attributed to A Davis.

At least 307 records · Page 17Linked to original sources
PubMed1987

Drug and vaccine development.

Some of the activities in chemotherapeutic research and vaccine development which WHO has initiated, participated, coordinated or funded are reviewed. WHO has interests in research, particularly, although by means exclusively, in all the communicable diseases and in applied vaccinology. Examples are given from various fields including progress in human trials of anti-sporozoite vaccines in malaria due to Plasmodium falciparum, chemotherapeutic studies on artemisine and halofantrine, pragmatic and systemic approaches to vaccination in leishmaniasis, recent work on the chemotherapy of leishmanial infections, African leishmaniasis and Chagas' disease, the anticipated impact of ivermectin in onchocerciasis control, studies on new macro- and microfilaricides, progress in the diarrhoeal diseases control programme, and the control of taeniasis/cysticercosis, ascariasis and hookworm through different delivery systems using population-based chemotherapy.

Animals↗
PubMed1987

Hair cell distributions in the normal human cochlea.

This supplement presents the results of a collaborative project between workers from several European nations. The study was started in order to provide data describing the distribution of the sensory hair cells in the normal human cochlea and to allow the evaluation of age-related changes in the hair cell density. Fifty-three cochleas (including nine from fetuses) were preserved by perilymphatic perfusion with fixative shortly after death. In the non-fetal material the hearing was clinically normal prior to death. Some subjects had audiograms available and these also had to be normal for their age for inclusion of the cochlea in the study. Dissection of cochleas permitted surface preparation techniques to be used to count the hair cells and allow the hair cell density to be described as inner or outer hair cells per mm. The total length in mm of each cochlea was also measured (Length). The location of each hair cell density count was defined as distance in mm from the base (Distance), distance in mm from the apex (Length minus Distance), or as a proportion of the total length of the cochlea when the location of that count was measured as distance from the base (Distance/Length). The material was allocated to one of six age bands. For each age band and at each point in the cochlea for which data existed the average hair cell density and its standard deviation were calculated. This allowed average cytocochleograms to be drawn for both inner and outer hair cells. The proportional method of representation of location within the cochlea gave the best fit of the available data and the proportional cytocochleograms are presented, although the data for all three methods are included in tabular form. The average cytocochleograms indicate a progressive age-related loss of outer hair cells. This loss was exacerbated at both the apical and basal ends of the cochlea. The overall loss was less marked for the inner hair cell population but was accentuated at the base, like that of the inner hair cells, although not at the apex. With the proportional datasets, and taking fetal age as zero, a model of hair cell loss was developed. A simple linear equation in the form: Hair cell density(i) = (Age in years X Age Coefficient(i)) + Constant(i) gave the best fit at each proportional location (i) for both inner and outer hair. The age coefficients and constants are given in tables for inner and outer hair cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Count↗
PubMed1986

Interactions between non-steroidal anti-inflammatory drugs and antihypertensives and diuretics.

Non-steroidal anti-inflammatory drugs (NSAIDs) may increase blood pressure and antagonise the effects of antihypertensive agents. They can cause salt and water retention and an increase in extracellular volume. NSAIDs also cause a decrease in prostaglandin synthesis in blood vessel walls which removes a direct vasodilatory influence and also increases the vascular response to vasoconstrictor stimuli. The hypotensive effects of frusemide and captopril are due in part to their stimulation of prostaglandin synthesis. Hence the antagonism of the hypotensive effect of these agents is probably due to NSAID-induced inhibition of prostaglandin synthesis. However, the interactions of NSAIDs with the other antihypertensive agents may not be related to inhibition of antihypertensive-induced release of prostaglandin but to independent and opposing actions of the NSAIDs on the various physiological mechanisms which regulate blood pressure. Clinicians should remain alert to these potential drug interactions.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1986

Multicentre clinical trials of benzimidazolecarbamates in human echinococcosis.

Studies coordinated by the World Health Organization were conducted in seven clinical centres on the chemotherapy of human echinococcosis with mebendazole, albendazole, and flubendazole. The first phase of these ended with the following conclusions.Treatment of 85 patients with mebendazole for cystic (Echinococcus granulosus) echinococcosis was successful in 8 patients and partially successful in 4 others. Flubendazole was effective in only one case of lung echinococcosis. Albendazole was successful in 5 of 30 patients treated and partially successful in 4 others. Further studies on new drugs or new formulations of existing benzimidazoles and on better forms of their application are needed. In the mean time, chemotherapy of human cystic echinococcosis should be restricted to inoperable cases.In 54 patients with E. multilocularis echinococcosis, it was confirmed that mebendazole therapy may arrest the development of the lesions. This treatment is therefore indicated in most cases of alveolar echinococcosis with or without surgery. However, further studies are needed to clarify the optimal regimen for mebendazole treatment and to explore the effectiveness of albendazole therapy.

Adolescent↗
PubMed1985

Manganese-phospholipid-stimulated protein kinase activity of human leukemic cells.

A protein kinase system with unusual characteristics was noted in extracts of HL-60 cells using endogenous proteins as substrates. This system exhibited a cation preference for manganese at an optimal concentration of 0.5 mM. Moderate activity was detectable with magnesium at an optimal concentration of 5.0 mM, but calcium was inactive. Activity was markedly stimulated by phospholipid, with phosphatidylglycerol and phosphatidylinositol exhibiting greater activity than phosphatidylserine. In isolated plasma membranes, the major substrate of this system was a 73-kDa protein, while cytoplasmic extracts exhibited larger amounts of a 42-kDa substrate. 73-kDa phosphorylating activity of membranes was comparably active at 0 and 31 degrees C, although in cytosol activity was greater at 31 degrees C. No 73-kDa protein phosphorylation was observed in the presence of Ca2+, Mg2+, and phosphatidylserine. Phosphoamino acid analysis of the 73-kD band revealed phosphothreonine and phosphoserine. The 42-kDa substrate was distinguishable from actin by two-dimensional gel electrophoresis, which disclosed that both major substrates were highly basic in the isoelectric focusing dimension. Protamine and histones (H2B greater than H1 greater than H3) exhibited phospholipid-stimulated phosphorylation in the presence of Mn2+, but phosvitin, casein, and vinculin were not substrates. High levels of phosphorylative activity involving the 73-kDa substrate were noted in nuclear extracts. Complex patterns of increase of this activity were noted in both cytosol and nuclear extracts following induction of differentiation with dimethyl sulfoxide, retinoic acid, or phorbol 12-myristate 13-acetate. This study thus demonstrated the presence of a previously undescribed type of protein kinase activity which exhibited alterations during leukemic cellular differentiation.

Cell Differentiation↗
PubMed1985

SCH 23390 may alter dopamine-mediated motor behaviour via striatal D-1 receptors.

SCH 23390 potently displaced the specific binding of 3H-piflutixol to D-1 sites in striatal membranes but haloperidol was only weakly effective. SCH 23390 weakly displaced specific 3H-spiperone binding to D-2 sites, but haloperidol was potent. SCH 23390 was more effective than haloperidol in inhibiting dopamine stimulated striatal adenylate cyclase activity. These results confirm the D-1 selectivity of SCH 23390. However, SCH 23390 inhibited apomorphine-induced stereotypy and climbing behaviour in rats with equal potency to haloperidol. Haloperidol dose-dependently increased striatal HVA and DOPAC concentrations without altering dopamine content. Low doses of SCH 23390 elevated striatal DOPAC concentrations but higher doses were without effect; striatal dopamine and HVA overall was unaffected by administration of SCH 23390. Haloperidol did not affect basal 3H-acetylcholine release from striatal slices but reversed the apomorphine-induced inhibition of 3H-acetylcholine release. SCH 23390 did not affect basal 3H-acetylcholine release nor did it reverse the apomorphine-induced inhibition of 3H-acetylcholine release. The ability of SCH 23390 to inhibit motor behaviour in the rat may be due to its action on D-1 receptors since the drug does not cause typical changes in parameters of striatal D-2 receptor function.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Partial characterization of solubilized platelet imipramine binding sites using a new probe, [3H]3-cyanoimipramine ([3H]Ro 11-2465).

Evidence suggests that [3H]imipramine labels the recognition site of the neuronal 5-hydroxytryptamine uptake mechanism. We are investigating the linkage between these binding sites and the carrier by biochemical characterization. [3H]Imipramine-labelled sites have been solubilized from outdated human platelets using the detergent digitonin. [3H]3-Cyanoimipramine binds persistently to these sites in the presence of Na+ at 4 degrees C. At higher temperatures, and in the absence of Na+, this ligand acts reversibly. We report the use of this pseudo-irreversible ligand in the initial molecular characterization of the recognition molecule. To confirm that this ligand occupies the [3H]imipramine-labelled sites, human platelets were prelabelled with 3-cyanoimipramine before incubating with [3H]imipramine. Only low affinity [3H]imipramine binding remained. The majority of the 3-cyanoimipramine was irreversibly bound under these conditions as shown by the use of the 3H compound. Gel permeation chromatography of [3H]3-cyanoimipramine-prelabelled platelet membranes solubilized with digitonin indicated a Stokes' radius of 6.3 nm. This is larger than values previously determined for cholate-solubilized sites. We conclude that [3H]3-cyanoimipramine will be useful for further purification and reconstitution studies.

Binding, Competitive↗
PubMed1985

Health peer outreach by high school students.

A health screening program was established in an inner-city New York public high school using the services of trained members of the student body as screeners. These students were trained to do a variety of health-related examinations and tests. Supervision and training were provided by a school health educator and members of a medical team from a nearby municipal hospital medical center. The primary goal was to reach, through peer involvement, those students who would be unlikely to interact with the routine health-care system. Of the 480 students receiving screening examinations, 291 were found to have abnormalities. In addition, a greater awareness of medical issues and available health-care facilities was seen among the student body. Through their training, the student screeners were exposed to various health-care fields, thus increasing their awareness of medical career potentials.

Adolescent↗
PubMed1985

Diagnosis of bone lesions by subtraction radiography.

Examiner diagnostic accuracy and response times were compared using subtraction and conventional radiography in a dog model. Osseous lesions were induced interproximally and through the mandibular buccal bone interradicularly and radicularly. Standardized preoperative and postoperative conventional radiographs of the induced lesions were compared to subtraction images of the same sites by 11 dentists. Examiners using the subtraction technique demonstrated improved diagnostic performance (P less than 0.001) and response times (P less than 0.001). Additionally, this method yielded a 30% reduction in equivocal diagnostic decisions. Data from this study suggest that subtraction radiography is a sensitive and accurate method to detect osseous lesions associated with periodontal diseases.

Alveolar Process↗
PubMed1985

Effect of praziquantel on hematuria and proteinuria in urinary schistosomiasis.

In five settlements on Lake Volta, Ghana, 230 persons infected with S. haematobium were treated with either 30 or 40 mg/kg of praziquantel. Both treatment regimes gave similar overall cure rates (60%) and reduction in geometric mean egg counts (92%) at a six-month follow-up. In this highly endemic area, 32% of the initial urine specimens were visibly bloody and only 4% remained bloody after treatment. Geometric mean egg counts of visibly bloody urine specimens were two to six times higher than normal appearing urine specimens. In children under 15 years of age, gross hematuria was reduced by 91% and hematuria as detected by reagent strips was reduced by 77% after treatment with praziquantel. Among adults, gross hematuria was reduced by 76% and hematuria as detected by reagent strips was reduced by 68%. Reduction was observed in 74% of all persons with 100 mg of protein/100 ml of urine or more prior to treatment. The cure rate with praziquantel was only 36.1% in children who had visibly bloody urine specimens associated with high geometric mean egg counts prior to treatment. The lowest cure rate (15.4%) was observed in persons with persistent hematuria and proteinuria after treatment although the geometric mean urinary egg count was reduced 84%. In infected individuals without hematuria or proteinuria prior to treatment, the cure rate was 96%. This study demonstrated that praziquantel reduced clinical signs due to S. haematobium infection as well as achieved a high cure rate and/or reduction of egg excretion. Conversely, individuals with clinical signs of hematuria and proteinuria had a lower cure rate with praziquantel than individuals without clinical signs.

Adolescent↗