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Biomedical subjects

P Clark

Publications and source records attributed to P Clark.

At least 199 records · Page 11Linked to original sources

Phenotype analysis of lymphocyte subsets in normal human bone marrow.

T-lymphocyte subsets in marrow aspirates taken from normal donors were analyzed with the use of monoclonal antibodies and flow cytometry. Peripheral blood specimens from the same donors were analyzed concurrently and served as controls. Eighty-six percent of CD8-positive cells from marrow expressed the pan-T-cell markers CD2 and CD3, compared with 91% and 81%, respectively, of CD8-positive cells from peripheral blood. Virtually all CD8-positive marrow lymphocytes, however, were negative for CD11b as opposed to peripheral blood, where 18% exhibited positivity for this marker. Further, a higher percentage of marrow CD8-positive T-lymphocytes expressed HLA-DR (15.4%) than did those from peripheral blood (4%). Marrow CD4-positive subsets did not differ substantially from those of peripheral blood. These results support the concept of a selective homing of CD8-positive T-cells to the marrow and indicate that CD8-positive T-cells in the marrow are effector T-cells.

Antibodies, Monoclonal↗

Screening for aminoglycoside auditory toxicity in the old.

1. We have investigated 22 patients receiving gentamicin, mean (s.d.) age 78 (6) years for auditory toxicity, using a standard audiometric technique in a sound-treated room (Study 1). 2. Use of a portable audiometer might allow a larger and more representative proportion of patients treated with aminoglycosides to be screened for ototoxicity. A method for detecting high frequency loss suitable for use in the ward was evaluated in 12 volunteers aged 27 (4) years (Study 2). 3. The error inherent in taking hearing at the start of treatment as a reference point was measured in 16 patients, aged 81 (8) years, prescribed non-ototoxic antibacterials (Study 3). 4. A significant (P = 0.05) reduction in hearing threshold was detected in Study 1, although psychometric tests revealed unchanged or improved ability to co-operate. This occurred only at 4000 Hz, the highest frequency used. The magnitude of this loss, mean 2.5 dB, was similar to that of the improvement in threshold detected (P = 0.0004) early in the course of treatment in Study 3. Thus, underestimation of ototoxicity is likely. 5. If a change of threshold of 10 dB or more is taken arbitrarily to represent a real change in hearing, then there was a significant excess of patients in Study 1 with losses at 4000 Hz only (P = 0.032). The six with such losses at this frequency were older than the rest. However, there was a significant (P less than 0.02) positive correlation between log mean predose serum gentamicin concentration and age. Thus, it remains to be determined whether presbyacusis sensitizes those hair cells which it does not destroy to toxic damage. 6. The cumulative dose of gentamicin (for a course of the duration given) was calculated according to published prescribing aids. There was no systematic reduction in the ratio of the dose recommended by a given aid to the dose prescribed in the six with hearing losses as defined above. 7. In Study 2, thresholds obtained at 6000 Hz in the open ward were, on average, 0.9 dB higher than in the sound treated room, but the effect of venue did not reach statistical significance. In the morning thresholds were marginally, but significantly (P = 0.04), lower than in the afternoon. Precision, as measured by the standard deviation of replicate determination, was independent of test conditions. Using multiple (ten) threshold determinations appeared to improve resolution.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Topographical control of cell behaviour: II. Multiple grooved substrata.

Electronics miniaturization techniques have been used to fabricate substrata to study contact guidance of cells. Topographical guidance of three cell types (BHK, MDCK and chick embryo cerebral neurones) was examined on grooved substrata of varying dimensions (4-24 microns repeat, 0.2-1.9 microns depth). Alignment to within 10 degrees of groove direction was used as our criterion for guidance. It was found that repeat spacing had a small effect (alignment is inversely proportional to spacing) but that groove depth proved to be much more important in determining cell alignment, which increased with depth. Measurements of cell alignment and examination by scanning electron microscopy showed that BHK cells and MDCK cells interacted differently with grooved substrata, and also that the response of MDCK cells depended on whether or not the cells were isolated or part of an epithelial cell island. Guidance by a multiple topographical cue is greater than could be predicted from cells' reactions to a single cue (Clark et al. Development 99: 439-448, 1987). Substratum topography is considered to be an important cue in many developmental processes. Cellular properties such as cytoskeletal organisation, cell adhesion and the interaction with other cells are discussed as being factors determining a cells susceptibility to topography.

Animals↗

The importance of the toes in walking.

The importance of well-functioning toes has long been recognised but has not previously been assessed in biomechanical studies. We have examined the weight-bearing function of the foot in 160 normal subjects by use of the pedobarograph. The function of the toes was assessed by reference to the time they were in contact with the ground and the peak pressures they exerted individually in comparison with other parts of the foot. The toes were in contact for about three-quarters of the stance phase of gait and exerted peak pressures similar to those of the metatarsal region. When the foot was bearing the second peak of total force, the area in contact with the ground (the metatarsal heads and toes) was decreasing.

Adolescent↗

Links between passive smoking and disease: a best-evidence synthesis. A report of the Working Group on Passive Smoking.

We reviewed the toxicologic, clinical, and epidemiologic evidence on the health effects of environmental tobacco smoke (ETS). For each type of exposure to environmental tobacco smoke we have sought articles in the English language reporting studies of effects on human health. Formal criteria that stressed study design, quality of execution and generalizability of results were used to select 116 scientifically admissible reports from over 2,900 articles. We concluded that: (a) there is strong evidence of an association between residential exposure to environmental tobacco smoke and both respiratory illness and reduction of lung function, and also between maternal smoking and reduced birth weight; (b) the weight of evidence is compatible with an association between active maternal smoking during pregnancy and increased infant mortality, and also between residential exposure to environmental tobacco smoke (primarily spousal smoking) and the risk of lung cancer; (c) there is evidence consistent with a relationship between exposure to environmental tobacco smoke in the workplace and respiratory symptoms, (d) the evidence is insufficient to implicate residential exposure to environmental tobacco smoke in relation to other forms of malignant disease or congenital malformations; (e) there is no evidence in the literature of an association between nonresidential exposure to environmental tobacco smoke and any form of cancer. Further studies are required to address the effects of exposure to environmental tobacco smoke, especially nonresidential exposure, in carcinogenesis and as a risk factor for atherosclerosis. Further work is also needed to improve measurement of exposure in such studies and to assess the importance of confounding factors.

Adolescent↗

Rapid detection of vaginal colonization with group B streptococci by means of latex agglutination.

Latex agglutination testing for colonization of the vagina with group B streptococci was carried out in 1100 patients. Samples underwent latex testing after 8 to 12 hours of preincubation in selective growth medium. This technique allowed a sensitivity of 91.8% and specificity of 97.6%. This study demonstrates the usefulness of latex agglutination testing in the detection of vaginal colonization with group B streptococci.

Female↗

A genetic study of von Recklinghausen neurofibromatosis in south east Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity.

A population based study of von Recklinghausen neurofibromatosis in south east Wales (population 668,100) identified 69 families with 135 affected members (prevalence 1/4950 of the population). In these families penetrance of the NF-1 gene was 100% by the age of five years. The genetic fitness of NF-1 sufferers was found to be reduced to 0.47, the effect being more marked in males than females (f = 0.31 and 0.60, respectively). Forty-one of 135 cases were judged to represent new disease mutations and the mutation rate was estimated to lie between 3.1 x 10(-5) and 10.4 x 10(-5). A parental age effect for new mutations was not found, nor was a maternal effect on disease severity.

Adolescent↗

Rhabdomyolysis and listeria monocytogenes.

Non-traumatic rhabdomyolysis occurs as a complication of a wide variety of infections and is often discovered as a result of the associated renal failure. We report a case of meningitis due to Listeria monocytogenes, an uncommon cause of infection in adults which was associated with rhabdomyolysis. This confirms a recent first case report of this association.

Female↗

Effect of prostaglandin on indomethacin-induced increased intestinal permeability in man.

This study examines whether NSAID induced disruption of small intestinal integrity is preventable by concomitant prostaglandin administration, and whether prostaglandins themselves interfere with intestinal permeability and absorption. Twelve subjects underwent testing following treatment as indicated: baseline, no treatment rioprostil, 300 micrograms, at -9 and -1 h indomethacin, 75 mg and 50 mg, at -9 and -1 h respectively rioprostil plus indomethacin, regimen as above. At 0800 h (0 h) subjects drink a solution containing 51CrEDTA 100 microCi, L-rhamnose 0.5 g, D-xylose 0.5 g and 3-O-methyl-glucose 0.2 g; this is followed by a 5-h urine collection. The amount of test substance in the urine reflects non-mediated intercellular and transcellular permeability, and passive and active carrier mediated transport systems, respectively. Permeation of L-rhamnose, D-xylose and 3-O-methyl-glucose is unaffected by rioprostil and/or indomethacin. Indomethacin significantly increases intestinal permeability to 51CrEDTA; coadministration of rioprostil, however, significantly decreases this detrimental effect of indomethacin. These findings suggest that prostaglandins are essential for maintaining small intestinal integrity in man and lend further support to the suggestion that NSAIDs damage the small intestine by reducing mucosal prostaglandin synthesis.

3-O-Methylglucose↗

Axial involvement in the seronegative enthesopathy and arthropathy syndrome and its progression to ankylosing spondylitis.

We studied prospectively the clinical and radiographic features of sacroiliac and spinal involvement in 20 patients with seronegative enthesopathy and arthropathy. This group was compared with 25 patients with a polyarticular onset form of juvenile rheumatoid arthritis (JRA) and 28 with definite ankylosing spondylitis (AS) of juvenile onset. A significant increasing proportion of patients with seronegative enthesopathy and arthropathy developed back complaints and radiographic sacroiliitis fulfilling the diagnostic criteria for AS from the 3rd-5th year of disease (47.1-75.0%) and thereafter (92.3%). Back complaints were rarely seen in JRA and, furthermore, sacroiliitis of the AS type nerve occurring in this group. There were no significant differences between the group with seronegative enthesopathy and arthropathy and juvenile AS, either at onset or through the years. Clinical and radiographic assessment of axial involvement in children at risk should include a careful analysis of symptoms, periodical measurements of the spinal flexion and, starting from the 3rd year, radiographs of the pelvis.

Adolescent↗

Meta-analysis of injectable gold in rheumatoid arthritis.

A pooled estimate of the magnitude of the benefit and side effects of injectable gold salts in rheumatoid arthritis was computed using meta-analysis based upon available evidence in the literature. Active joint count, grip strength, functional capacity, hemoglobin concentration and erythrocyte sedimentation rate (ESR) were pooled. The change in percentage in favor of gold (adjusted for placebo) was as follows: active joint count 30.1%, (p less than 0.00001), grip strength 13.7% (p less than 0.013), functional capacity 13% (p less than 0.0005), hemoglobin concentration 5.3% (p less than 0.02), and ESR 19.6% (p less than 0.02). Pooling of side effects gave the following results: side effect withdrawals were 11% (p less than 0.01), dermatitis occurred in 15% and proteinuria in 0.7% more patients than in the placebo group.

Arthritis, Rheumatoid↗

Retinal pigment epithelial cells in culture produce retinal vascular mitogens.

Conditioned medium from human retinal pigment epithelial cells in culture significantly stimulated the proliferation of subcultured bovine retinal capillary endothelial cells, pericytes, and freshly isolated retinal microvessels. The vascular mitogenic activity enhanced that of retinal crude extract. No evidence emerged of an inhibitor of microvascular cellular proliferation produced by retinal pigment epithelial cells.

Animals↗