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Biomedical subjects

C Davis

Publications and source records attributed to C Davis.

At least 163 records · Page 9Linked to original sources

Project Solo: an independent practitioner initiative for confidential self-assessment of quality.

Project Solo, a grassroots organization of independent physicians, has developed a unique method of confidential self-assessment of quality. Participating physicians can use the data to improve their own practices and to have a strong, credible voice for retaining and promoting the strengths of independent practices in providing medical care. In a pilot project, 56 independent physicians in Project Solo were given bar-coded, postage-paid survey forms of patient satisfaction to distribute to 100 patients. The population for this pilot study was the 35 physicians with patients returning at least one survey. A total of 1858 surveys (53% of surveys given to physicians) were returned, representing a variety of rural and urban practices in 19 states. The mean percentage of responses rated "excellent" to survey items from Project Solo physicians is similar to the percentages reported for this survey in other studies. We conclude that Project Solo serves as an effective and efficient model for gathering patient satisfaction data and can be further developed as a tool for gathering clinical outcome and other quality measurement data in the solo and small group practice setting.

Demography↗

The Problem of Thrombocytopenia after Hematopoietic Stem Cell Transplantation.

Thrombocytopenia after hematopoietic stem cell transplantation (HSCT) is associated with an increased risk of bleeding and utilization of significant resources. This review presents an analysis of risk factors associated with delayed platelet engraftment. The retrospective analysis included 1,468 recipients of autologous or allogeneic transplants treated between January 1, 1990 and July 1, 1995. Risk factors associated with delayed platelet engraftment after autologous HSCT included use of marrow rather than peripheral blood as the source of stem cells, being transplanted for acute myeloid leukemia rather than other diseases, positive patient serology for cytomegalovirus and the presence of infection post-transplant before engraftment. Risk factors associated with delayed platelet engraftment after allogeneic marrow transplantation included unrelated as opposed to related donor transplants, being transplanted for diseases other than chronic myelogenous leukemia, increased age, onset of acute graft-versus-host disease (GVHD), male gender, the administration of methotrexate for GVHD prophylaxis and the presence of infection before engraftment. Delayed platelet recovery is associated with decreased survival after both autologous and allogeneic transplants. Management of delayed platelet recovery by transfusion of blood products requires significant medical resources and is of some risk to the patients. Further development of new strategies may safely reduce the need for blood products. These include peripheral blood stem cell transplants (allogeneic and autologous), new algorithms for administering routine platelet transfusions and investigative biological agents for stimulating megakaryocytopoiesis. Further studies may elucidate the cause of increased platelet consumption associated with infection and GVHD.

Journal Article↗

Chimeric synthetic peptides as antigens for detection of antibodies to HIV-1 and HIV-2.

Two chimeric peptides incorporating immunodominant sequences from both HIV-1 (LGIWGCSGKLICTT) and HIV-2 (LNSWGCAFRQVCHT) were synthesized. Peptides KS1-KS2 and KS2-KS1 represented sequences from the two viruses in both possible orders, separated by two glycine residues as spacers. These peptides were evaluated as antigens in an ELISA using a panel of specimens derived from HIV-1 (n = 25) and HIV-2 (n = 25) infected individuals and seronegative people (n = 38). The results were compared to plates coated with individual peptides KS1 and KS2 and to plates coated with two peptides (KS1 and KS2) together. Data demonstrated that individually, KS1 and KS2, are good antigens and can detect antibodies to their respective viruses quite efficiently. However, when coated together, their ability to detect antibodies to both HIV-1 and HIV-2 was reduced, as evidenced by a decrease in OD values obtained. The chimeric peptides KS1-KS2 and KS2-KS1 detected antibodies to HIV-1 and HIV-2; however, their sensitivity of detection was variable and dependent upon the order of their sequence. For both peptides, antibodies directed to the C-terminal portion were detected with higher sensitivity than those directed to the N-terminal part of the peptides. This may be related to peptide adsorption to the solid surface and epitope accessibility to the antibodies. Such chimeric antigens may be very useful for simultaneous detection of antibodies to HIV-1 and HIV-2.

AIDS Serodiagnosis↗

Interindividual and interspecies variation in hepatic microsomal epoxide hydrolase activity: studies with cis-stilbene oxide, carbamazepine 10, 11-epoxide and naphthalene.

Microsomal epoxide hydrolase (HYL1) is a single-gene enzyme responsible for the hydrolysis of epoxides derived from the oxidative metabolism of xenobiotics. Variation in HYL1, therefore, may be an important determinant of drug toxicity. We have investigated HYL1 enzyme kinetics in six different species including man, for which a liver bank genotyped for polymorphisms in exons 3 and 4 of the HYL1 gene was used. Activity was measured by radiochromatography with high specific activity radiolabeled substrates, cis-stilbene oxide (CSO) and carbamazepine 10,11-epoxide (CBZ-E). In addition, naphthalene was used to investigate the hydrolysis of an epoxide (naphthalene 1,2-epoxide [N-E] generated in situ. There was marked species variation in enzyme activity that was substrate dependent. CSO was rapidly hydrolyzed by microsomes from all species, the rank order of specific activity being human > rabbit > dog > rat > hamster > mouse. In contrast, hydrolysis of CBZ-E was only observed with human liver microsomes. CBZ-E was only a weak (IC50 = 1 mM) inhibitor of CSO hydrolysis. The hydrolysis of N-E, determined as the diol-to-total metabolite ratio, was human > rabbit > dog > hamster > mouse > rat. Intraspecies variation in man was 4-fold, 7-fold and 2-fold for CSO, CBZ-E and N-E, respectively: none of this variation could be directly accounted for by the HYL1 polymorphisms in exons 3 and 4. These data emphasize the need for careful toxicokinetic evaluation of species used in the safety evaluation of compounds likely to form epoxide intermediates in vivo.

Adult↗

Clinical trials: testing of adult chemical heating pad.

Chemical packs are recent innovations in the delivery of dry heat. Because these delivery systems do not have any mechanism for verifying temperature during application, research to determine their safety seems warranted. The purpose of this study was to measure the skin temperature of adults during a 30-minute application of the MediHeat adult heating pad (MH-AHP). Seventy-seven subjects received a 30-minute application of the MH-AHP to their backs while lying in both supine and prone positions. The mean skin temperature in both positions was 101 degrees F. There were significant differences, however, in minimum and maximum skin temperature between positions. Subjects in the prone position had significantly higher maximum skin temperature and significantly lower minimum skin temperature than subjects in the supine position. It is possible that the prone position allows for more air flow over the MH-AHP and that more heat was generated causing the higher maximum temperature. This explanation does not account for the lower minimum temperature. There were no significant differences in perception of heat between the positions at either 5 minutes or 30 minutes. Findings suggest that caution is necessary when applying heating devices that depend on air circulation for heat generation.

Adult↗

Characterization of a life-cycle-stage-regulated membrane protein tyrosine phosphatase in Trypanosoma brucei.

We report the first characterization of plasma-membrane-bound tyrosine phosphatase activity in the haemoprotozoan. Trypanosoma brucei. Several enzymic properties of the membrane fraction were identical to other protein tyrosine phosphatases (PTPases), such as (a) insensitivity to inhibitors of other protein phosphatases, including tetramisole, sodium tartrate and okadaic acid, (b) inhibition by sodium vanadate, and (c) activation by spermidine. Additionally, T. brucei PTPase activity presented two novel features, an acidic pH optimum at pH 4.0-5.0 and a very low Km value (2.5 nM) for the specific synthetic substrate, Tyr(P)Raytide. Higher Km values of 170 nM for Tyr(P)-RCML (RCML, reduced, carboxamidomethylated and maleylated lysozyme) and of 3 mM for the non-specific inorganic substrate p-nitrophenyl phosphate, suggested that the PTPase activity of T. brucei was substrate specific. Reconstitution experiments on bloodstream-stage membrane proteins revealed that three polypeptides of 148, 115 and 72 kDa contained vanadate-inhibitable PTPase activity. Modulator assays revealed that the 72-kDa protein was responsible for the observed spermidine stimulation, but indicated that the modulator profile of the 148-kDa protein was most similar to the whole membrane fraction. Furthermore, the PTPase activity of T. brucei was life-cycle-stage regulated. Neither the whole membrane fraction nor the reconstituted proteins of the procyclic insect stage dephosphorylated tyrosine residues.

Animals↗

Macromolecular arrangement in the aminoacyl-tRNA.elongation factor Tu.GTP ternary complex. A fluorescence energy transfer study.

The distance between the corner of the L-shaped transfer RNA and the GTP bound to elongation factor Tu (EF-Tu) in the aminoacyl-tRNA.EF-Tu.GTP ternary complex was measured using fluorescence energy transfer. The donor dye, fluorescein (Fl), was attached covalently to the 4-thiouridine base at position 8 of tRNAPhe, and aminoacylation yielded Phe-tRNAPhe-Fl8. The ribose of GTP was covalently modified at the 2'(3') position with the acceptor dye rhodamine (Rh) to form GTP-Rh. Formation of the Phe-tRNAPhe-Fl8.EF-Tu.GTP-Rh ternary complex was verified both by EF-Tu protection of the aminoacyl bond from chemical hydrolysis and by an EF-Tu.GTP-dependent increase in fluorescein intensity. Spectral analyses revealed that both the emission intensity and lifetime of fluorescein were greater in the Phe-tRNAPhe-Fl8.EF-Tu.GTP ternary complex than in the Phe-tRNAPhe-Fl8.EF-Tu.GTP-Rh ternary complex. These spectral differences disappeared when excess GTP was added to replace GTP-Rh in the latter ternary complex, thereby showing that excited-state energy was transferred from fluorescein to rhodamine in the ternary complex. The efficiency of singlet-singlet energy transfer was low (10-12%), corresponding to a distance between the donor and acceptor dyes in the ternary complex of 70 +/- 7 A, where the indicated uncertainty reflects the uncertainty in dye orientation. After correction for the lengths of the probe attachment tethers, the 2'(3')-oxygen of the GTP ribose and the sulfur in the s4U are separated by a minimum of 49 A. This large distance limits the possible arrangements of the EF-Tu and the tRNA in the ternary complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Energy Transfer↗

Relationship between evoked potentials and clinical status in spinal cord ischemia.

STUDY DESIGN AND METHODS: Sciatic neurogenic motor-evoked potentials, spinal evoked potentials, and somatosensory-evoked potentials were recorded in 12 anesthetized dogs that had arterial ischemia of the lumbar cord produced by ligation of segmental arteries. The presence or absence of the above-mentioned potentials was compared with the clinical status of repeated wake-up tests. RESULTS: Although these results were complicated, sciatic neurogenic motor-evoked potential was more sensitive to the spinal cord ischemia and was a better predictor of clinical outcome than spinal evoked potential and somatosensory-evoked potential. However, the presence was not a guarantee of normal function. The initial morphologic change of these potentials secondary to ischemia consisted of a decrease in amplitude and in the number of peaks without a shift of latency. CONCLUSIONS: The present study suggests that the peripheral neurogenic motor-evoked potential is a better warning system for spinal cord ischemia and that its adoption may contribute to the prevention of cord ischemia during spinal surgery, whereas somatosensory-evoked potential and spinal evoked potential cannot be indices.

Animals↗

Trypanosoma brucei and Trypanosoma cruzi: life cycle-regulated protein tyrosine phosphatase activity.

Recent evidence that Trypanosoma brucei synthesizes stage-regulated phosphotyrosine containing proteins and protein kinases stimulated us to assay bloodstream and insect stages of Trypanosoma cruzi and both pleomorphic and monomorphic clones of T. brucei for tyrosine phosphatase activity. Bloodstream and procyclic insect stages of T. brucei contained a 55-kDa protein that cross-reacted with monoclonal antibodies directed against the human placental tyrosine phosphatase PTP1B. Protein lysates of all life cycle stages of both trypanosomes dephosphorylated a nonspecific substrate, pNPP, and the specific substrate Tyr(P)Raytide. Dephosphorylation of Tyr(P)Raytide was effectively inhibited only by sodium vanadate, a specific phosphotyrosine phosphatase inhibitor, but pNPP activity was also inhibited by sodium fluoride (NaF) in lysates of T. brucei and by NaF and sodium tartrate in lysates of T. cruzi, suggesting that their respective lysates also contained serine/threonine and acid phosphatase activities. Fractionation studies revealed that most of this activity was in the cytosol. Stage regulation of tyrosine phosphatase activity in T. cruzi was strongly suggested by differences in the optimal pH for tyrosine phosphatase activity (7.0 for amastigotes and epimastigotes; 5.0 for trypomastigotes). We conclude that both species of trypanosomes synthesize tyrosine phosphatases and propose that identification and characterization of the enzymes responsible for this phosphatase activity could provide information about trypanosomal virulence or the regulation of trypanosomal growth and differentiation.

Animals↗

Obsessive compulsiveness and physical activity in anorexia nervosa and high-level exercising.

Although excessive physical activity and obsessive compulsiveness are both prevalent in anorexia nervosa (AN), to date, the association between these two factors has not been systematically investigated. The aim of the present study was to investigate the relationship between obsessive compulsiveness and both behavioral and psychological aspects of exercise in women with AN, and to compare them to a nonclinical sample of females classified as either moderate or high-level exercisers. Results indicated that obsessive compulsiveness, weight preoccupation, and pathological aspects of exercise were significantly related to the level of physical activity among the eating disorder patients. For the high-level exercisers, only obsessive compulsiveness was significantly related to the amount of physical activity. The findings are discussed in terms of a model in which physical activity, starvation, and obsessive compulsiveness are reciprocally and dynamically related, with each factor creating a destructive bidirectional loop that is resistant to change and difficult to break. We propose that this self-perpetuating loop may be a significant influence in the development and maintenance of eating disorders in a certain subgroup of women.

Adult↗

Activation of protein kinase C by the capsaicin analogue resiniferatoxin in sensory neurones.

Resiniferatoxin and capsaicin are sensory neurone-specific excitotoxins that operate a common cation channel in nociceptors. Resiniferatoxin is structurally similar to capsaicin and to phorbol esters. Specific [3H]-resiniferatoxin binding, which was detected in the membrane (KD value 1.8 +/- 0.2 nM) but not cytosolic fraction of rat dorsal root ganglia, could not be displaced by phorbol 12,13-dibutyrate. Conversely, resiniferatoxin did not displace [3H]phorbol 12,13-dibutyrate binding in either the cytosolic or membrane fraction. Resiniferatoxin and capsaicin both caused translocation of protein kinase C in dorsal root ganglion neurones (EC50 value 18 +/- 3 nM). This translocation was greatly reduced but not abolished, in the absence of external Ca2+, suggesting that it was secondary to Ca2+ entry. Resiniferatoxin also caused direct activation of a Ca(2+)- and lipid-dependent kinase (or kinases) in the cytosolic fraction of dorsal root ganglia, at concentrations (100 nM to 10 microM) higher than required for displacement of [3H]resiniferatoxin binding or translocation of protein kinase C. Capsaicin (up to 10 microM) was unable to mimic this effect. These data imply that although resiniferatoxin-induced translocation of protein kinase C in dorsal root ganglion neurones was mainly indirect, it also caused direct activation of a protein kinase C-like kinase in these cells.

Animals↗