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Biomedical subjects

M White

Publications and source records attributed to M White.

At least 271 records · Page 15Linked to original sources
PubMed1993

Maintaining continence in nursing home residents through the application of industrial quality control.

Supervisory nurses in seven nursing homes were taught how to implement a quality control management system that permitted the time-efficient assessment of how well a prompted voiding toileting program continued to be implemented by indigenous nursing aides. Random-hour wet checks taken during the 6-month management period revealed a reduction in wetness from 43% to 21% (p < .0001), which was sustained over the full 6-month period.

Aged↗
PubMed1993

Effective concentration 50 for propofol with and without 67% nitrous oxide.

The Effective Blood Concentration (EC) of propofol required to prevent response to surgical incision was determined in 65 ASA I or II female patients breathing either 100% oxygen or 67% N2O in oxygen. Propofol was administered via a microcomputer-controlled infusion system programmed to maintain the blood propofol concentration at predetermined target values. The blood propofol concentrations predicted by the micro-computer were validated by measurement of whole blood propofol concentration. Predicted and measured concentrations differed during infusion of propofol, but became similar after discontinuing the infusion for at least 90 s, suggesting that equilibration within the central compartment was incomplete during infusion. The response to the initial incision was observed and probit analysis used to determine the predicted blood concentration at which 50% of patients responded. The predicted EC50 for propofol/N2O/O2 and propofol/O2 was 4.5 micrograms ml-1 and 6.0 micrograms ml-1 respectively, and the measured EC50 propofol/N2O/O2 and propofol/O2 was 5.36 micrograms ml-1 and 8.1 micrograms ml-1, 67% nitrous oxide in oxygen reducing the predicted EC50 by 25% and the measured EC50 of propofol by 33%. The predicted EC may be more representative of the equilibrated concentration in the central compartment and thus reflective of tissue propofol concentrations.

Adolescent↗
PubMed1993

Synergistic combinations of Ro 11-8958 and other dihydrofolate reductase inhibitors with sulfamethoxazole and dapsone for therapy of experimental pneumocystosis.

We compared Ro 11-8958, an analog of trimethoprim (TMP) with improved antimicrobial and pharmacokinetic properties, other dihydrofolate reductase (DHFR) inhibitors, sulfamethoxazole (SMX), and dapsone (DAP) in the treatment of Pneumocystis carinii pneumonia in an immunosuppressed rat model. In contrast to previous reports, high dosages of the DHFR inhibitors were used in combination with fixed, low dosages of SMX (3 mg/kg of body weight per day) or DAP (25 mg/kg/day). When administered alone at these dosages, SMX and DAP reduced the median P. carinii cyst count about 5- to 15-fold. Ro 11-8958, TMP, and diaveridine used at a dosage of 20 mg/kg/day with SMX were only slightly more effective than SMX used alone. However, administration of these DHFR inhibitors at a dosage of 100 mg/kg/day with SMX lowered the cyst count about 500- to 1,000-fold, indicating a synergistic effect. Little or no synergism was found when other DHFR inhibitors (pyrimethamine, cycloguanil, and tetroxoprim) were combined with SMX. Regimens of Ro 11-8958 at a dosage of 20 mg/kg/day with DAP and of TMP or diaveridine used at a dosage of 100 mg/kg/day with DAP showed comparable anti-P. carinii activity, lowering the cyst count 100- to 200-fold. By contrast, Ro 11-8958 administered at a dosage of 100 mg/kg/day with DAP reduced the cyst count > 1,000-fold. Thus, the experimental approach used here enables the rat model of pneumocystosis to be used to compare synergistic combinations of antifolate drugs. The favorable results achieved with Ro 11-8958 indicate that it should be considered for clinical trials.

AIDS-Related Opportunistic Infections↗
PubMed1993

SH2 domains exhibit high-affinity binding to tyrosine-phosphorylated peptides yet also exhibit rapid dissociation and exchange.

src homology 2 (SH2) domains of intracellular signaling molecules such as phospholipase C-gamma and phosphatidylinositol 3'-kinase-associated protein p85 represent recognition motifs for specific phosphotyrosine-containing regions on activated growth factor receptors. The binding of SH2 domains to activated growth factor receptors controls the interaction with signaling molecules and the regulation of their activities. In this report, we describe the kinetic parameters and binding affinities of SH2 domains of p85 toward short phosphotyrosine-containing peptides with the amino acid sequence motif YMXM, derived from a major insulin receptor substrate, IRS-1, by using real time biospecific interaction analysis (BIAcore). Associations were specific and of very high affinity, with dissociation constants of 0.3 to 3 nM, between phosphopeptides and the two separate SH2 domains contained within p85. Nonphosphorylated peptides showed no measurable binding, and the interactions were specific for the primary sequence very close to the phosphotyrosine residue. Moreover, the interactions between phosphopeptides and SH2 domains of other signaling molecules were of much lower affinity. Interestingly, the binding of the SH2 domains to the tyrosine-phosphorylated peptides was of high affinity as a result of a very high on rate, of 3 x 10(7) to 40 x 10(7)/M/s; at the same time, the rate of dissociation, of 0.11 to 0.19/s, was rapid, allowing for rapid exchange of associating proteins with the tyrosine phosphorylation sites.

Amino Acid Sequence↗
PubMed1993

Overview of clinical trials in congestive heart failure.

Heart failure is the only cardiovascular disorder which is increasingly prevalent in North America. Several large clinical trials have emerged within the past 10 years. The results from some of these trials have had a significant impact on the way congestive heart failure is recognized and treated. The objective of this review is not to review exhaustively all recent clinical trials in heart failure but to present the most important ones selected because of their impact on how one understands and treats congestive heart failure in 1993. The results, as well as some important pathophysiological considerations related to these trials, will be addressed.

Clinical Trials as Topic↗
PubMed1993

Audit of public health medicine: the northern region's approach.

Public health doctors are required to audit their work, a principle endorsed by the Faculty of Public Health Medicine. Although general concepts of audit in clinical medicine are likely to apply to public health medicine, the practical problems are likely to be different. Public health medicine, therefore, needs to experiment with approaches to audit until general principles are established. The implementation of public health medicine audit in the Northern Region is reviewed here, highlighting the establishment of structures (e.g. a public health medicine audit promotion group and audit link-persons), processes (e.g. study days, exchange of information) and outcomes (e.g. audits undertaken and standards devised). The foundations for audit of public health medicine have been built upon wide debate and consultation, locally written documents detailing the arguments and making practical suggestions for change, ownership of policy-making decisions by a regional forum of public health doctors, day-to-day responsibility resting in an audit group, a heavy emphasis on communication including the gauging of opinions, attitudes and behaviour by survey, a perception that public health medicine has the same rights and obligations towards audit as other medical specialties, and the view that audit in our specialty will require time and patience to implement. The challenge remains of ensuring the implementation of cost-effective audit in the routine practice of public health medicine.

Data Collection↗
PubMed1993

Identification of P-glycoprotein/multidrug resistance genes from model organisms.

Using degenerate oligonucleotides from conserved portions of the ATP-binding domain of the active transporter genes, several new members of this gene superfamily have been cloned from Drosophila, Saccharomyces cerevisiae, and E. coli DNA. The Drosophila and E. coli genes contain two sets of transmembrane domains and two ATP-binding domains, whereas the yeast gene contains single transmembrane and ATP-binding domains. All three genes show a high degree of similarity to the mammalian P-glycoprotein/multidrug resistance (MDR) genes. The E. coli sequence is the only known transporter gene containing both ATP and transmembrane domains in a single open reading frame. While the function of these sequences has not been determined, they may prove to be useful for developing a model to study the function of P-glycoproteins.

Adenosine Triphosphate↗
PubMed1993

GP trainees and MMR immunisation.

Three months after the launch of the MMR programme in the United Kingdom and the Republic of Ireland, a postal questionnaire was sent to all GP scheme trainees in both Northern Ireland and the Republic of Ireland. The response rate was 81%. All trainees were enthusiastic about promoting MMR immunisation; with 27% favouring compulsory immunisation. 9% had never seen a patient with measles. This did not alter their attitude towards the beneficial effects of MMR immunisation. Of pre-practice year trainees 26% felt their level of knowledge of immunisation was inadequate, 59% claimed to have received no education on immunisation during their vocational training to date. This may reflects deficiencies in their medical curriculum to-date. 95% of third-year trainees indicated that their practice experience had been the source of at least some of their education on immunisation. Only 46% of trainees in the Republic of Ireland were aware of their Department of Health's aims in launching the MMR immunisation campaign.

Family Practice↗
PubMed1992

Amino terminus of the interleukin-8 receptor is a major determinant of receptor subtype specificity.

Interleukin-8 (IL-8) is a key mediator in the migration of neutrophils from the circulation to the site of inflammation in the tissue. IL-8 is secreted by many cell types in response to proinflammatory stimuli such as interleukin 1, tumor necrosis factor, and lipopolysaccharide and is a potent chemoattractant and activator of neutrophils. Neutrophil activating peptide-2 (NAP-2) and melanoma growth-stimulatory activity (MGSA/GRO) are structurally and functionally related to IL-8 and, like IL-8, bind to specific G protein-coupled receptors on neutrophils. In the present study two closely related cloned IL-8 receptor subtypes are characterized by expression of the cDNA clones in monkey kidney cells (COS-7) or chinese hamster ovary cells and analysis of their ligand binding profiles. Both receptor subtypes bind 125I-labeled IL-8 with similar high affinity, however, the F3R receptor binds IL-8 exclusively, while the 4Ab receptor binds both IL-8 and MGSA/GRO with high affinity and NAP-2 with lesser affinity. Furthermore, we demonstrate with the use of intersubtype chimeric receptors that the specificity of ligand binding to both IL-8 receptor subtypes is dictated by the heterogeneous NH2-terminal domain. The F3R receptor is representative of a restricted IL-8 receptor subtype, and 4Ab represents a nonrestricted receptor subtype. It is proposed that these subtypes be named IL-8 receptors alpha and beta, respectively.

Amino Acid Sequence↗
PubMed1992

Models of insulin action on metabolic and growth response genes.

In ongoing studies aimed at elucidating the mechanism of insulin action on the expression of genes that modulate glucose utilization and cell growth, we have focused on the inductive effect of insulin on transcription of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the early growth response gene, Egr-1. Insulin acutely stimulates the expression of both genes in 3T3 adipocytes; however, in primary adipocytes, chronic insulin exposure has opposing effects on the expression of these genes. GAPDH mRNA is decreased in the epididymal fat cells of diabetic animals and is increased over control levels when insulin is replaced, while Egr-1 mRNA levels are increased in diabetic animals. These observations, coupled with the finding that insulin-stimulated Egr-1 gene transcription is impaired in a Chinese hamster ovarian (CHO) cell line that displays normal metabolic responses but impaired ability to regulate DNA synthesis, support the conclusion that insulin regulation of Egr-1, a growth response gene, and GAPDH, a metabolic response gene, are mediated by distinct pathways. We present evidence that supports the role of protein phosphorylation in mediating the effect of insulin on activation of Egr-1 and GAPDH gene transcription.

3T3 Cells↗
PubMed1992

Characterization of the bovine peripheral lymph node homing receptor: a lectin cell adhesion molecule (LECAM).

The phenomenon of tissue-specific homing of lymphocyte populations has been most clearly shown in larger domestic animals, such as the sheep and cow, yet the molecular interactions which control these processes in these animals have not been defined. Here we tested the cross-reactivity of four anti-human peripheral lymph node homing receptor (LECAM-1) (also known as LAM-1, LEC-CAM-1, Leu-8, TQ-1, or human equivalent of gp90 MEL-14) antibodies on bovine lymphocytes. These antibodies stained all bovine neutrophils and monocytes, and variable numbers of peripheral blood lymphocytes, as determined by flow cytometry. In young calves (less than 1 month old) virtually all circulating lymphocytes expressed LECAM-1, whereas the percentage of positive lymphocytes in older animals (greater than 1 year) varied from 17%-67%. Bovine LECAM-1 was rapidly lost from the cell surface of PMA-activated and chymotrypsin-treated cells. Anti-LECAM-1 monoclonal antibody blocked greater than 80% of bovine lymphocyte binding to peripheral lymph node high endothelial venules (HEV). Since the lectin domain of LECAM-1 is thought to mediate lymphocyte-HEV adhesion, we sought to establish further the similarity of the bovine, mouse, and human molecules by comparing nucleotide sequences in this region of the molecule. The polymerase chain reaction (PCR) was used to specifically clone the bovine lectin domain from single-strand cDNA. Subsequent sequencing showed an identity of greater than 80% at the nucleotide level with the human and mouse molecules. The predicted amino acid sequences were also highly conserved. Though striking similarities were seen between the bovine, mouse and human molecule, indicating evolutionary conservation of this family of proteins, notable differences were detected. The nucleotide sequence of the bovine lectin domain predicts one additional N-linked glycosylation site compared to mouse and human. Preliminary analysis suggested a more tissue-restricted expression of LECAM-1 in the compared to the human and mouse, which correlates with a better separation of lymphocyte homing phenotypes seen in these larger animals. Virtually all peripheral lymph node lymphocytes in 6-month-old calves expressed LECAM-1, whereas, ileal Peyer's patch lymphocytes were predominantly negative. Finally, by testing anti-human LECAM-1 antibodies in a different species we have established the co-expression of antigenic epitopes on leucocyte LECAM-1 and a molecule(s) expressed by endothelial cells.

Amino Acid Sequence↗
PubMed1992

Transient expression of somatostatin peptide is a widespread feature of developing sensory and sympathetic neurons in the embryonic rat.

Previous studies from this and other laboratories demonstrated that many embryonic sensory ganglion cells in the rat transiently express the catecholamine synthesizing enzyme tyrosine hydroxylase (TH), a trait not expressed by most mature sensory neurons. We, therefore, sought to determine whether transient expression was uniquely associated with catecholaminergic traits, or, alternatively, whether embryonic ganglion cells transiently expressed peptidergic properties as well. Of the four peptides examined (somatostatin [somatotropin release inhibiting factor] (SRIF), galanin (Gal), calcitonin gene-related peptide (CGRP), and substance P (SP)), only SRIF was found to be transiently expressed during early stages of sensory gangliogenesis. Surprisingly, SRIF immunoreactivity was observed in virtually all cranial and spinal sensory ganglion cells on embryonic day (E) 12.5. In addition to perikaryal labeling, intense SRIF immunoreactivity was also observed in the central and peripheral processes of E12.5 sensory neurons, suggesting the peptide may be released from nerve endings. The time course of SRIF appearance in cranial ganglion cells paralleled that previously described for TH, and double-labeling studies revealed extensive co-localization of these two phenotypes. By E16.5, however, the number of neurons expressing SRIF had diminished markedly, indicating that SRIF is only transiently expressed by most sensory neurons during early stages of ganglion development. An unexpected finding was that transient expression of SRIF is also a prominent feature of sympathetic ganglion cells; however, the temporal pattern of staining in the sympathetic and sensory ganglia differed substantially. Whereas virtually no SRIF staining was observed in E12.5 sympathetics, the vast majority of cells in the E16.5 superior cervical ganglion (SCG) were labeled. This contrasted sharply with the adult SCG, in which only low levels of SRIF expression were found. These findings demonstrate that SRIF peptide is transiently expressed at high levels in peripheral sensory and sympathetic neurons during embryogenesis. The time course and widespread distribution of SRIF expression indicates that the peptide may play a role in early stages of ganglion cell growth and development. Moreover, these data, in conjunction with previous studies demonstrating SRIF immunoreactivity in developing central neurons, suggest that transient expression of this peptide is a common property of diverse neuronal cell types.

Animals↗
PubMed1992

Preconception and preimplantation diagnosis for cystic fibrosis.

Preimplantation diagnosis provides couples at high genetic risk the possibility of avoiding genetic disease without the need for prenatal diagnosis and selective abortion of the affected pregnancy. Following extensive background work on the reliability of genetic diagnosis in a single cell, we offered on a research basis preimplantation diagnosis to five couples at risk for offspring with the delta-F508 mutation (the major mutation causing cystic fibrosis). There was no detrimental effect from polar body removal on either fertilization or preimplantation development. Genetic analysis, undertaken in 22 polar bodies and 15 corresponding blastomeres, identified 21 embryos of which ten were transferred.

Biopsy↗
PubMed1992

Postoperative analgesia using a computerised infusion of alfentanil following aortic bifurcation graft surgery.

A Psion microcomputer controlled infusion system for alfentanil was assessed for the provision of post-operative analgesia in 14 patients who had undergone aortic bifurcation graft surgery. The system employed a pharmacokinetic model working in real time to deliver any selected target plasma concentration of alfentanil. The alfentanil infusion system was used for a mean time of 39 hours and for 96% of this time, patients were scored as having no pain or only mild pain. Severe pain was recorded for only 0.05% of the study time. The use of a pharmacokinetic delivery system may offer a convenient and simple method of providing postoperative analgesia with alfentanil.

Adult↗