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Biomedical subjects

P Wilson

Publications and source records attributed to P Wilson.

At least 145 records · Page 8Linked to original sources
PubMed1997

Association of insulin-like growth factor-I with body composition, weight history, and past health behaviors in the very old: the Framingham Heart Study.

OBJECTIVES: We examined correlates of insulin-like growth factor-I (IGF-I), an indicator of growth hormone levels, to identify factors associated with higher levels of IGF-I in old age. DESIGN: Nested study of cross-sectional correlates and early-life predictors of IGF-I level. SETTING: A longitudinal cohort study, the Framingham Heart Study. PARTICIPANTS: A total of 790 men and women (mean age 78.5, range 72-94), who had weight, waist and hip circumferences measured at the time of IGF-I measurement. MEASUREMENTS: Association of IGF-I with weight, fat distribution, functional status, nutritional indicators, and past health behaviors was assessed. We also examined IGF-I in relation to body composition derived from dual energy X-ray absorptiometry. RESULTS: IGF-I levels declined with age in both men and women. However, low IGF-I did not show expected associations with low lean mass and increased body fat. Current functional status and grip strength were not associated with IGF-I Low IGF-I was associated with weight loss in men; the strongest associations were with indicators of poorer nutritional status in both men and women. Levels of IGF-I in old age did not vary by past health behaviors. CONCLUSION: Although IGF-I declined with age, these data from the Framingham Heart Study did not show expected cross-sectional associations of weight, body fat, and lean mass. The strongest associations were between IGF-I and nutritional indicators. These results suggest caution may be warranted with regard to use of IGF-I as an indicator of growth hormone.

Aged↗
PubMed1997

Dose equivalence and bronchoprotective effects of salmeterol and salbutamol in asthma.

BACKGROUND: Salbutamol is the most widely prescribed short acting beta 2 agonist and salmeterol is the first long acting inhaled beta 2 agonist. The dose equivalence of salmeterol and salbutamol is disputed. Estimates of weight-for-weight dose ratio have ranged from 1:2 to 1:16. A study was undertaken to clarify the true dose ratio. METHODS: The bronchoprotection afforded against repeated methacholine challenge by inhaled salmeterol 25 micrograms and 100 micrograms and salbutamol 100 micrograms and 400 micrograms was compared in a randomised, double blind, placebo controlled, crossover trial. Subjects were 16 stable asthmatics with a baseline forced expiratory volume in one second (FEV1) of > or = 65% predicted, screening concentration provoking a fall in FEV1 of 20% (PC20FEV1) of < or = 8mg/ml, and a shift in PC20FEV1 of more than two doubling concentration steps following inhalation of salbutamol 400 micrograms. On five separate occasions subjects underwent methacholine challenge before and 30 and 120 minutes after drug administration. PD20FEV1 was calculated for each challenge. FEV1 at 90 minutes after drug administration was also recorded. RESULTS: Bronchoprotection afforded by salmeterol was increased at 120 minutes compared with 30 minutes and protection by salbutamol was decreased. Protection by both doses of salmeterol was similar to salbutamol 100 micrograms at 30 minutes but significantly greater at 120 minutes. FEV1 at 90 minutes was significantly greater after salmeterol 100 micrograms than after placebo, but there were no other significant differences between treatments. Maximal observed protection was equivalent for salmeterol 100 micrograms and salbutamol 400 micrograms. CONCLUSIONS: The data are compatible with a weight-for-weight dose ratio for salmeterol:salbutamol of < or = 1:4.

Administration, Inhalation↗
PubMed1997

Genetic characterization of the role of the two HOX proteins, Proboscipedia and Sex Combs Reduced, in determination of adult antennal, tarsal, maxillary palp and proboscis identities in Drosophila melanogaster.

Both Proboscipedia (PB) and Sex Combs Reduced (SCR) activities are required for determination of proboscis identity. Here we show that simultaneous removal of PB and SCR activity results in a proboscis-to-antenna transformation. Dominant negative PB molecules inhibit the activity of SCR indicating that PB and SCR interact in a multimeric protein complex in determination of proboscis identity. These data suggest that the expression pattern of PB and SCR and the ability of PB and SCR to interact in a multimeric complex control the determination of four adult structures. The absence of PB and SCR expression leads to antennal identity; expression of only PB leads to maxillary palp identity; expression of only SCR leads to tarsus identity; and expression of both PB and SCR, which results in the formation of a PB-SCR-containing complex, leads to proboscis identity. However, the PB-SCR interaction is not detectable in vitro and is not detectable genetically in the head region during embryogenesis, indicating the PB-SCR interaction may be regulated and indirect. This regulation may also explain why ectopic expression of SCR(Q50K) and SCR do not result in the expected transformation of the maxillary palp to an antennae and proboscis, respectively. Previous analysis of the requirements of SCR activity for adult pattern formation has shown that ectopic expression of SCR results in an antenna-to-tarsus transformation, but removal of SCR activity in a clone of cells does not result in a tarsus-to-arista transformation. Here we show in five independent assays the reason for this apparent contradictory requirement of SCR activity in tarsus determination. SCR activity is required cell nonautonomously for tarsus determination. Specifically, we propose that SCR activity is required in the mesodermal adepithelial cells of all leg imaginal discs at late second/early third instar larval stage for the synthesis of a mesoderm-specific, tarsus-inducing, signaling factor, which after secretion from the adepithelial cells acts on the overlaying ectodermal cells determining tarsus identity. This study characterizes a combinatorial interaction between two HOX proteins; a mechanism that may have a major role in patterning the anterior-posterior axis of other animals.

Animals↗
PubMed1997

Our problem.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1997

The completeness and accuracy of patient record transfer between practices.

OBJECTIVES: In addition to the paper record, most general practitioners now use a parallel electronic record system on their practice computer. When a patient changes practice at present, the written records are transferred from the patient's previous practice to the next. An up to date computer generated summary or print out should also be sent. Our aim was determine the completeness and accuracy of this process of patient record transfer. DESIGN: A survey of an opportunistic sample of one hundred patient records in transit between general practices during a single week. Accuracy of information transferred was assessed by examining the records. Further analysis of discrepancies was conducted by one of the authors (FS) to assess their clinical significance. SETTING: September 1995, primary care department of Lanarkshire Health Board. RESULTS: Only 46% of practices transfer the complete record compared to the 85% of practices with computers which would have been expected to do so. Even in those which transferred a paper copy of the electronic record, a total of 51% showed discrepancies between the computer and manual format in recording of some or all of the following: diagnoses, prescribing data and the results of investigations. CONCLUSION: Practices should ensure all relevant data is transferred when a patient moves from one practice to another. The current arrangements do not ensure that this occurs.

Continuity of Patient Care↗
PubMed1997

Phase I and pharmacokinetic study of tirapazamine (SR 4233) administered every three weeks.

Tirapazamine (SR 4233; 3-amino-1,2,4-benzotriazine-1,4-di-N-oxide) is a bioreductive agent exhibiting up to 200 x greater toxicity for hypoxic cells as compared to oxygenated cells. In murine studies, a selective increase in tumor kill was observed when tirapazamine was coadministered with other agents, notably cisplatin. A Phase I study of single-agent tirapazamine administered i.v. every 3 weeks was conducted to determine the toxicity of a schedule for use with systemic chemotherapy. A total of 28 patients were given 50 courses of tirapazamine at doses ranging from 36-450 mg/m2. No tumor responses were observed. Reversible deafness and tinnitus were dose-limiting, with ototoxicity observed in 1 of 6 patients treated at 330 mg/m2, 1 of 4 patients treated at 390 mg/m2, and 3 of 3 patients treated at 450 mg/m2. Muscle cramps, nausea, and vomiting were also observed. Pharmacokinetic studies revealed a greater than dose-proportional increase in the area under the plasma concentration x time curve (AUCs) of the two major metabolites. Patients who developed ototoxicity generally showed higher plasma AUC values for the parent drug and metabolites. The mean plasma tirapazamine AUC at 330 mg/m2 was 1026.5 microgram/ml x min (range 863. 8-1252.3), but no pharmacokinetic data are available for the solitary patient who developed otoxicity at this dose level. These AUC values were in the (estimated) range required for therapeutic effect in murine studies. Ototoxicity was not observed when the AUC of tirapazamine was equal to or less than 1252 microgram/ml x min. The dose of 330 mg/m2 was therefore chosen as an appropriate level for combination chemotherapy studies.

Adult↗
PubMed1996

Hydrogen bonding and molecular surface shape complementarity as a basis for protein docking.

A geometric docking algorithm based upon correlation analysis for quantification of geometric complementarity between protein molecular surfaces in close interfacial contact has been developed by a detailed optimization of the conformational search of the algorithm. In order to reduce the entire conformation space search required by the method a physico-chemical pre-filter of conformation space has been developed based upon the a priori assumption that two or more intermolecular hydrogen bonds are intrinsic to the mechanism of binding within protein complexes. Donor sites are defined spatially and directionally by the positions of explicitly calculated donor hydrogen atoms, and the vector space within a defined range about the donor atom-hydrogen atom bond vector. Acceptor sites are represented spatially and directionally by the van der Waals molecular surface points having normal vectors within a predefined range of vector space about the acceptor atom covalent bond vector(s). Geometric conditions necessary for the simultaneous hydrogen bonding interaction between both sites of functionally congruent hydrogen bonding site pairs, located on the individual proteins, are then tested on the basis of a transformation invariant parameterization of the site pair spatial and directional properties. Sterically acceptable conformations defined by interaction of functionally, spatially, and directionally compatible site pairs are then refined to a maximum contact of complementary contact surfaces using the simplex method for the angular search and correlation techniques for the translational search. The utility of the spatial and directional properties of hydrogen bonding donor and acceptor sites for the identification of candidate docking conformations is demonstrated by the reliable preliminary reduction of conformation space, the improved geometric ranking of the minimum RMS conformations of some complexes and the overall reduction of CPU time obtained.

Algorithms↗
PubMed1996

Introducing an integrated nursing research programme.

The move towards evidence-based medicine, the standards being set by purchasers and the greater involvement of nurses in higher education have all led to an increasing interest in research among nurses. This paper describes how one NHS trust sought to develop a clinical nursing research programme and integrate this within its overall research strategy.

Clinical Nursing Research↗
PubMed1996

Plasticity of cutaneous primary afferent projections to the spinal dorsal horn.

Reorganization of the somatotopic map in the spinal dorsal horn may be elicited by a variety of deafferenting lesions, including transection of peripheral nerves or dorsal roots, or the application of neurotoxins. While such lesions give rise to a variety of neurochemical and morphological changes in the dorsal horn, collateral sprouting of intact primary afferents appears to be minimal. Recently, intraaxonal injection of neurobiotin has allowed visualization of the entire spinal arborization of single A beta primary afferent fibers in animals where the somatotopy of the relevant region of dorsal horn has also been mapped. In contrast to the somatotopic precision of the terminal fields of peripheral nerves suggested by transganglionic tracing, these studies have shown that afferents make connections many millimeters rostral and caudal to the region where their receptive field is represented in the somatotopic map. Intracellular recording from dorsal horn neurons has further shown that these long-ranging projections make functional, but weak, synaptic connections. Thus the functional somatotopic reorganization that follows nerve lesions in mature animals might be explained simply by an increased synaptic efficacy of these existing projections. In contrast to the negligible sprouting of intact A beta primary afferents, those undergoing axonal regeneration exhibit dense collateral sprouting into deafferented regions of the dorsal horn, particularly the superficial laminae, where the terminal arbors of many small (A delta and C) nociceptive afferent fibres degenerate following peripheral nerve lesions. The inappropriate connections made by these collateral sprouts may partly underlie the painful sequelae of nerve injury in man.

Animals↗
PubMed1996

Emotional support for cancer patients: what do patients really want?

For many cancer patients and their families the experience of cancer is an intensely stressful one. Emotional support is important for most cancer patients during their illness and can be gained from different people and services. This study evaluates patients' attitudes to different sources of support and rates their satisfaction with sources already used. A total of 431 patients completed a questionnaire covering the use of different sources, including individuals, support groups and information sources. The questionnaire also incorporated validated measurements of anxiety, depression and locus of control. The results revealed that the three most important sources of emotional support were senior registrars (73%) and family (73%), followed by consultants (63%). Patients would prefer doctor- and nurse-led support groups to patient only-led groups (26% vs 12%). Pamphlets, such as the BACUP booklets, proved the most important of the informational sources sought (50%). A total of 86% of patients were satisfied or very satisfied with the emotional support received. Patients who expressed dissatisfaction with their emotional support were significantly more likely to be anxious and depressed (P < 0.001). Patients who used information sources were more likely to have a higher locus of control over the course of their disease. These results show how important the doctor's role is in the provision of emotional support.

Adolescent↗
PubMed1996

Soluble CD23 protein in the peritoneal fluid of patients with endometriosis.

Activated B cells are known to produce soluble CD23 protein (sCD23) from their membranes. We recently showed a higher concentration of sCD23 in the serum of patients with endometriosis. As the commonest site of endometriosis is the peritoneal cavity, we sought to evaluate the concentration of sCD23 in the peritoneal fluid of 47 fertile symptomatic women with endometriosis and 35 fertile women without endometriosis. Endometriosis was diagnosed by laparoscopy and confirmed by histopathology. There was a statistically significant difference between the sCD23 concentrations in the endometriosis and control groups (P < 0.05). When endometriosis was defined based on the revised American Fertility Society (AFS) Score, patients with mild (AFS 1 and II) but not severe (AFS III and IV) endometriosis showed a higher and significant difference in the concentration of sCD23 when compared with the controls (P < 0.05). There was no significant correlation between the peritoneal fluid concentration of sCD23 and the phase of the menstrual cycle. We conclude that the concentration of sCD23 is higher in the peritoneal fluid of patients with endometriosis when compared with the controls, suggestive of B cell activation in patients with endometriosis. Furthermore, mild endometriosis is immunologically more active than severe endometriosis as defined by the current classification.

Ascitic Fluid↗