Targeting high risk groups. Neighborhood organization for pediatric asthma management in the Neighborhood Asthma Coalition.
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Biomedical subjects
Publications and source records attributed to D Harrison.
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The Nurse Executive Council at a 540-bed community teaching health center planned and implemented Shared Governance in a 10-bed Medical Intensive Care Unit (MICU). Paid time was provided for nurses to take part in one of four councils. After a pilot year resulting in satisfaction with job autonomy and input into decision-making, staff reaffirmed their commitment to shared governance as a permanent "way of life" in the MICU. During the second year, patient care assistants and unit clerks were integrated into the Councils and staff began serving as consultants to other units and institutions.
The structure of the Candida rugosa lipase determined at 2.06-A resolution reveals a conformation with a solvent-accessible active site. Comparison with the crystal structure of the homologous lipase from Geotrichum candidum, in which the active site is covered by surface loops and is inaccessible from the solvent, shows that the largest structural differences occur in the vicinity of the active site. Three loops in this region differ significantly in conformation, and the interfacial activation of these lipases is likely to be associated with conformational rearrangements of these loops. The "open" structure provides a new image of the substrate binding region and active site access, which is different from that inferred from the structure of the "closed" form of the G. candidum lipase.
Direct sequencing of polymerase chain reaction (PCR)-amplified genomic DNA from a patient with spondyloepiphyseal dysplasia and precocious osteoarthritis revealed a single-base change in exon 11 of the type II procollagen gene (COL2A1), which produces an Arg-->Cys mutation in one allele. The proband is a member of a large Chilean kindred presenting with chondrodysplasia of the hips, knees, shoulders, elbows, and spine associated with severe, early-onset osteoarthritis. All affected individuals exhibit mildly short stature; in addition, five out of seven affected family members display shortened metacarpals or metatarsals. DNA from affected and unaffected family members was PCR-amplified and analysis of restriction digests of the products determined that the mutation segregated with the disease with a lod score of 2.2 at zero recombination. The mutation, which resides in the triple-helical region of type II procollagen at amino acid position 75, is the second example of an Arg-->Cys mutation in the COL2A1 gene in heritable cartilaginous disease and is the first example of a point mutation in the amino terminal region of the alpha 1(II) chain, that results in a spondyloepiphyseal dysplastic phenotype.
The skin affords an excellent model of human carcinogenesis because a variety of lesions from benign tumours to invasive malignancy, with or without metastatic potential, are commonly found, and are accessible to biopsy. To date, few genetic alterations have been observed in skin neoplasia. In this study we have used a recently developed monoclonal antibody (DO7) to examine p53 protein expression in a wide variety of benign and malignant skin lesions. Benign skin lesions were negative, but a significant number of malignant epithelial lesions showed detectable p53; 56% of squamous carcinomas and 42% of basal cell carcinomas were positive. A smaller proportion of dysplastic epithelial lesions were positive (27%), and only 3.6% of malignant melanomas were positive. Thus, although detectable p53 protein is a common occurrence in malignant epithelial lesions, it does not correlate with the malignant phenotype or with metastatic potential. The finding of a lower proportion of positivity in dysplastic lesions, and absence of staining in benign tumours, suggests that p53 mutation may be involved in the progression towards invasive malignancy in human squamous skin lesions.
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Patterns of public sector health service utilisation in relation to severity and weekday or weekend occurrence were identified for children from Khayelitsha with diarrhoeal disease. The current organisation of local services is inappropriate for the provision of basic primary care for these children. Given the inadequate access to appropriate care, caregivers select their health service options rationally. This paper recommends that a 24-hour rehydration unit be established in Khayelitsha to improve the effectiveness and appropriateness of the management of these children.
The mobile nature of the population of Khayelitsha makes it imperative that opportunities for immunisation of children are exploited at every visit to health services. Previous studies have demonstrated a high incidence of missed opportunities for immunisation at curative health services. The occurrence of undetected opportunities for immunisation are compared at two primary care institutions: one in which curative and preventive services are provided separately, and one in which these functions are integrated. Far fewer opportunities for immunisation were missed at the integrated service, underscoring the urgency of integrating child health services throughout the country.
An analysis of the origins and outcome of the Gluckman Commission is relevant to the current health service debate in South Africa. Fundamental to the report's recommendations was the establishment of a unitary health service responsible for all health care functions within the Union of South Africa. On this proposal rested the success of the other key recommendations. The sequence of events following the publication of the report demonstrated that piecemeal restructuring, determined primarily by political considerations, failed. Unless policy-makers today are committed to a unitary health system with democratic control, current initiatives to restructure health services will probably remain parochial, contributing little to the improvement of health care for all South Africans.
A series of protocols were developed for a commercially available automated workstation to prepare samples for amplification of DNA by the polymerase chain reaction (PCR) on automated thermal cyclers, to load PCR products onto agarose electrophoretic gels and to carry out dideoxynucleotide sequencing of DNA templates. The protocols and the software programs developed reduced by two-thirds the time required to carry out the procedures manually. The programs and protocols also improved the quality and the consistency of both the PCR products and the sequencing reactions.
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Two genes encode the CD16 low affinity IgG FcR. CD16-I (Fc gamma RIII-1) is expressed on PMN as a phosphatidylinositol-glycan anchored glycoprotein. CD16-II (Fc gamma RIII-2) is expressed on NK cells and macrophages as a transmembrane glycoprotein associated with CD3 zeta or Fc epsilon RI-gamma. NK cells spontaneously release soluble CD16-II from the cell surface and this is enhanced by activation with phorbol ester. In this study, we demonstrate that a metalloprotease is involved in the spontaneous and PMA-induced release of CD16-II from NK cells. 1,10-phenanthroline, an inhibitor of Zn(2+)-dependent metalloproteases, efficiently inhibits CD16-II release. 1,7-phenanthroline, an inactive analogue that doesn't chelate Zn2+ or other divalent metal cations, and inhibitors of serine proteases do not affect spontaneous or PMA-induced release of CD16-II. Murine P815 mastocytoma cells transfected with human CD16-II cDNA shed membrane CD16, and 1,10-phenanthroline inhibits this process. P815 transfectants expressing CD16-II molecules with truncated cytoplasmic domains also release soluble receptors, indicating that the cytoplasmic segment of CD16-II is not required for interaction with the protease or the cytoskeleton. By contrast, 1,10-phenanthroline does not inhibit PMA-induced release of CD16-I glycoprotein from PMN, indicating a different mechanism of release for this phosphatidylinositol-glycan anchored molecule. Prior studies have demonstrated that NK cells are activated via the inositol phosphate pathway after engagement of CD16-II by immune complexes or Ig-coated tumor cell targets. A membrane metalloprotease with substrate specificity for CD16-II that is activated by PKC stimulation may provide a mechanism for releasing the immune complex or target from the effector cells and halting signal transduction.
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The effect of gastric surgery on the pharmacokinetics of ranitidine was studied in six dogs, all serving as their own controls. Prior to and after surgery, each dog received a single oral dose (5 mg/kg of body weight) of a ranitidine solution. The surgery consisted of partial gastrectomy (antrectomy) and truncal vagotomy. Ranitidine plasma and urine concentrations were measured by reversed-phase ion-pair liquid chromatography with UV detection. Pharmacokinetic parameters were estimated by noncompartmental data analysis techniques. Gastric surgery tended to slow the absorption of ranitidine as reflected by a slight increase of the time necessary to reach the peak plasma concentration. The maximum observed plasma concentration was slightly lowered. The amount of drug absorbed remained unchanged as reflected by no change in the AUCs. Other parameters such as mean residence time, elimination half-life, apparent oral clearance, and fraction excreted unchanged in the urine remained unchanged. However, due to the small number of animals and the considerable intersubject variability, none of these trends reached statistical significance.
The paper considers bone-marrow repopulation experiments with injected mixtures of two types, A and B, of genetically marked donor cells. The covariance of the proportions of type A erythrocytes and lymphocytes is analysed as the sum of two components, under a stratified binomial model allowing the proportions of type A cells to vary in postulated strata of the mixture and with the assumption that the genetic marker does not influence cell development. The ratio of the two components is not experimentally estimable, but each of them has an interesting "demographic" interpretation. Possible inferences about certain "two-cell probabilities" are derived, and the experimental findings that necessitated the stratified model are illustrated.