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Biomedical subjects

R Shaw

Publications and source records attributed to R Shaw.

At least 55 records · Page 3Linked to original sources
PubMed1999

Spoligotyping in molecular epidemiology of tuberculosis in Ghana.

OBJECTIVES: Molecular epidemiological studies of Mycobacterium tuberculosis in high prevalence areas in sub-Saharan Africa are hampered by the difficulty of culturing organisms from clinical samples. This study aimed to evaluate for application in a developing country, a modification of a novel polymerase chain reaction (PCR) based molecular epidemiological typing method, termed spoligotyping. METHODS: DNA extraction from sputum was followed by PCR amplification of spacers between direct repeats in the M. tuberculosis genome, and hybridization to a range of the 53 known spacer sequences. RESULTS: Sputum from 175 patients in the Ashanti region of Ghana were collected, and satisfactory spoligotyping results were obtained in 159. A total of 100 different spoligotype patterns were observed with 84 patients having unique patterns and the remainder falling into 16 clusters. A number of epidemiologically linked cases were shown to be unrelated on the basis of different spoligotype patterns, but epidemiological links were not found to explain clusters. Comparison of spoligotyping of DNA extracted from sputum with restriction fragment length polymorphism (RFLP) from mycobacterial culture in a subset of 25 patients, indicated that spoligotyping was less discriminatory than RFLP, Sixteen spoligotype patterns were shown to comprise 2 3 different RFLP patterns. CONCLUSIONS: This study suggests that the PCR based technique of spoligotyping can be applied successfully to DNA extracted from sputum collected in the setting of a developing country, but that this is less discriminatory than RFLP. Spoligotyping is particularly useful when used to support conventional epidemiology since a proportion of false epidemiological associations can be identified.

Adult↗
PubMed1999

Impedance cardiography-derived hemodynamic responses during baroreceptor testing with amyl nitrite and phenylephrine: a validity and reliability study.

Baroreflex (BR) testing with phenylephrine (PE) and amyl nitrite (AN) provided an opportunity to evaluate the ability of impedance cardiography (IC) to track the rapid hemodynamic (HD) changes elicited by these drugs. The AN response was measured after inhalation and the PE response was measured after a bolus injection in 19 subjects on two occasions. High reliability was observed for all of the HD measures. Blood pressure (BP), peripheral resistance (PR), and preejection period (PEP) decreased significantly after administration of AN, whereas heart rate (HR) and cardiac output (Q) increased. BP and total PR increased significantly after administration of PE; HR and Q decreased and PEP did not change significantly. Stroke volume did not change significantly with either drug. The BR slope was reliably elicited with AN and PE. The IC and Finapres BP consistently detected short-term changes in HD responses to AN and PE. The pharmacological interventions demonstrated that IC measures followed the course predicted by the actions of the drugs. Change in PEP and dZ/dt reflected increased contractility. The BR sensitivity was also reproducible.

Adult↗
PubMed1999

Reduced tolerance to acute renal ischemia in mice with a targeted disruption of the osteopontin gene.

BACKGROUND: Mice with a targeted disruption of the osteopontin gene through homologous recombination in embryonic stem cells have recently been generated and shown to be characterized by unaltered fertility and normal embryonic and postnatal development, including renal development, but altered osteoclastogenesis from spleen progenitors. The lack of detectable pathological manifestations in kidneys of mice with the targeted disruption of the osteopontin gene (opn -/-) makes them an excellent model for studies of pathophysiological processes that are thought to be accompanied by changes in renal osteopontin expression. It has previously been suggested that osteopontin may play an important role in the pathophysiology of acute renal failure, thus prompting this study. METHODS: Wild-type and opn -/- mice were subjected to 30 minutes of renal ischemia and were studied 24 hours later. RESULTS: Control opn +/+ mice showed a significant retention of blood urea nitrogen and creatinine, which is indicative of the development of ischemic acute renal dysfunction. This was accompanied by a 2.7-fold increase in the immunodetectable osteopontin compared with sham-operated control. Animals with the disrupted osteopontin gene exhibited ischemia-induced renal dysfunction, which was twice as pronounced as that observed in mice with the intact osteopontin response to stress. In addition, the structural damage to the ischemic kidneys obtained from opn -/- mice was more pronounced than that observed in similarly treated wild-type mice. This was associated with the augmented expression of inducible nitric oxide synthase and the prevalence of nitrotyrosine residues in kidneys from opn -/- mice versus wild-type counterparts. In vitro studies with proximal tubular cells subjected to hypoxia in the presence of OPN, but not OPN with deleted arginine-glycine-aspartic acid (RGD) domain, resulted in cytoprotection. CONCLUSIONS: The comparative analysis of functional and morphological sequelae of acute renal ischemia in opn +/+ and opn -/- mice provides strong evidence of renoprotective action of osteopontin in acute ischemia.

Acute Disease↗
PubMed1999

New York 1 and Sin Nombre viruses are serotypically distinct viruses associated with hantavirus pulmonary syndrome.

New York 1 virus (NY-1) and Sin Nombre virus (SN) are associated with hantavirus pulmonary syndrome (HPS). NY-1 and SN are derived from unique mammalian hosts and geographic locations but have similar G1 and G2 surface proteins (93 and 97% identical, respectively). Focus reduction neutralization assays were used to define the serotypic relationship between NY-1 and SN. Sera from NY-1-positive Peromyscus leucopus neutralized NY-1 and SN at titers of >/=1/3,200 and </=1/400, respectively (n = 12). Conversely, SN-specific rodent sera neutralized NY-1 and SN at titers of <1/400 and 1/6,400, respectively (n = 13). Acute-phase serum from a New York HPS patient neutralized NY-1 (1/640) but not SN (<1/20), while sera from HPS patients from the southwestern United States had 4- to >16-fold-lower neutralizing titers to NY-1 than to SN. Reference sera to Hantaan, Seoul, and Prospect Hill viruses also failed to neutralize NY-1. These results indicate that SN and NY-1 define unique hantavirus serotypes and implicate the presence of additional HPS-associated hantavirus serotypes in the Americas.

Animals↗
PubMed1999

Rotavirus capsid protein VP5* permeabilizes membranes.

Proteolytic cleavage of the VP4 outer capsid spike protein into VP8* and VP5* proteins is required for rotavirus infectivity and for rotavirus-induced membrane permeability. In this study we addressed the function of the VP5* cleavage fragment in permeabilizing membranes. Expressed VP5* and truncated VP5* proteins were purified by nickel affinity chromatography and assayed for their ability to permeabilize large unilamellar vesicles (LUVs) preloaded with carboxyfluorescein (CF). VP5* and VP5* truncations, but not VP4 or VP8*, permeabilized LUVs as measured by fluorescence dequenching of released CF. Similar to virus-induced CF release, VP5*-induced CF release was concentration and temperature dependent, with a pH optimum of 7.35 at 37 degrees C, but independent of the presence of divalent cations or cholesterol. VP5*-induced permeability was completely inhibited by VP5*-specific neutralizing monoclonal antibodies (2G4, M2, or M7) which recognize conformational epitopes on VP5* but was not inhibited by VP8*-specific neutralizing antibodies. In addition, N-terminal and C-terminal VP5* truncations including residues 265 to 474 are capable of permeabilizing LUVs. These findings demonstrate that VP5* permeabilizes membranes in the absence of other rotavirus proteins and that membrane-permeabilizing VP5* truncations contain the putative fusion region within predicted virion surface domains. The ability of recombinant expressed VP5* to permeabilize membranes should permit us to functionally define requirements for VP5*-membrane interactions. These findings indicate that VP5* is a specific membrane-permeabilizing capsid protein which is likely to play a role in the cellular entry of rotaviruses.

Animals↗
PubMed1999

Use of bar code readers and programmable keypads to improve the speed and accuracy of manual data entry in the clinical microbiology laboratory: experience of two laboratories.

AIM: To assess the effect of the use of bar code readers and programmable keypads for entry of specimen details and results in two microbiology laboratories. METHODS: The solutions selected in each laboratory are described. The benefits resulting from the implementation were measured in two ways. The speed of data entry and error reduction were measured by observation. A questionnaire was completed by users of bar codes. RESULTS: There were savings in time and in reduced data entry errors. Average time to enter a report by keyboard was 21.1 s v 14.1 s for bar coded results entry. There were no observed errors with the bar code readers but 55 errors with keystroke entries. The laboratory staff of all grades found the system fast, easy to use, and less stressful than conventional keyboard entry. CONCLUSIONS: Indirect time savings should accrue from the observed reduction in incorrectly entered data. Any microbiology laboratory seeking to improve the accuracy and efficiency of data entry into their laboratory information systems should consider the adoption of this technology which can be readily interfaced to existing terminals.

Consumer Behavior↗
PubMed1999

Genetic medicine: an experiment in community-expert interaction.

This project tested a two-way model of communication between lay groups and experts about genetic medicine in Perth, Western Australia. Focus group discussion with community group participants was followed by a communication workshop between community group participants and experts. Four groups of concerns or themes emerged from discussion: clinical considerations; legislative concerns; research priorities, and ethical and wider considerations. Community group concerns are not always met by the actions of "experts". This is, in part, because of the differing life-worlds of each group. However, the communication workshop showed the potential of two-way communication for both lay and expert members in understanding the others' viewpoint. Further, the approach developed here offers one possible way for community groups to participate in a substantial way in policy formulation processes.

Attitude to Health↗
PubMed1999

Asthma management with HFA-BDP (Qvar).

This report reviews the role of hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP; Qvar, 3M, Laughborough) in the management of asthma, based on pharmacokinetic, efficacy and safety clinical trial data presented at a satellite symposium to the European Respiratory Society in 1998. Qvar provides equivalent efficacy and safety to chlorofluorocarbon-BDP at about half the dose.

Anti-Asthmatic Agents↗
PubMed1998

Anticoagulation is unnecessary after biological aortic valve replacement.

BACKGROUND: Opinion differs as to whether anticoagulation is beneficial in preventing ischemic stroke in the early postoperative period after biological aortic valve replacement (AVR). The purpose of this study was to determine whether early anticoagulation with heparin and warfarin confers any significant advantage for patients undergoing such replacement. METHODS AND RESULTS: Patients undergoing biological AVR between 1987 and 1996 were divided retrospectively into 2 groups based on their postoperative anticoagulation. Group A (109 patients) received heparin followed by warfarin for 3 months (prothrombin time, 20 to 25 seconds). Group B (76 patients) received no postoperative anticoagulation. Patients were followed for cerebral ischemic events, bleeding, repeat operation, hospital stay, and survival. There were 5 (4.6%), 3 (2.8%), and 12 (11%) postoperative cerebral ischemic events for group A at time points of < 24 hours, 24 hours to 3 months, and > 3 months, respectively; for group B patients, 3 (3.9%), 2 (2.6%), and 9 (11.8%) events were seen during the same respective time periods. There were no statistically significant differences for ischemic events during any of these time periods for the 2 groups. Bleeding complications occurred in 10 (9.2%) group A and 7 (9.2%) group B patients. Mean hospital stay was 12 days for both groups. Repeat operative AVR was required in 6 (5.5%) group A and 7 (9.2%) group B patients. A comparison of Kaplan-Meier survival rates between groups A and B (mean follow-up, 47 +/- 26 and 59 +/- 30 months, for groups A and B, respectively) was not statistically significant (P = 0.60). Survival rates were 93%, 84%, and 62% at 1, 5, and 7 years for group A and 87%, 74%, and 67% for group B, respectively. CONCLUSIONS: Early anticoagulation after AVR confers no advantage in the prevention of early cerebral ischemic events after biological AVR. No disadvantage in terms of bleeding or prolonged hospital stay was incurred by early anticoagulation. Long-term valve function and survival were not adversely affected by withholding early anticoagulation. We conclude that early anticoagulation after biological AVR is unnecessary.

Aged↗
PubMed1998

beta3 Integrins mediate the cellular entry of hantaviruses that cause respiratory failure.

Newly emerged hantaviruses replicate primarily in the pulmonary endothelium, cause acute platelet loss, and result in hantavirus pulmonary syndrome (HPS). We now report that specific integrins expressed on platelets and endothelial cells permit the cellular entry of HPS-associated hantaviruses. Infection with HPS-associated hantaviruses, NY-1 and Sin Nombre virus (SNV), is inhibited by antibodies to beta3 integrins and by the beta3-integrin ligand, vitronectin. In contrast, infection with the nonpathogenic (no associated human disease) Prospect Hill virus was inhibited by fibronectin and beta1-specific antibodies but not by beta3-specific antibodies or vitronectin. Transfection with recombinant alphaIIb beta3 or alphav beta3 integrins rendered cells permissive to NY-1 and SNV but not Prospect Hill virus infection, indicating that alphaIIb beta3 and alphav beta3 integrins mediate the entry of NY-1 and SNV hantaviruses. Furthermore, entry is divalent cation independent, not blocked by arginine-glycine-aspartic acid peptides and still mediated by, ligand-binding defective, alphaIIb beta3-integrin mutants. Hence, NY-1 and SNV entry is independent of beta3 integrin binding to physiologic ligands. These findings implicate integrins as cellular receptors for hantaviruses and indicate that hantavirus pathogenicity correlates with integrin usage.

Animals↗
PubMed1998

Vasopressin-induced disruption of actin cytoskeletal organization and canalicular function in isolated rat hepatocyte couplets: possible involvement of protein kinase C.

The effect of vasopressin (VP) on canalicular function and hepatocellular morphology, with particular regard to actin cytoskeletal organization and the concomitant plasma membrane bleb formation, was studied in isolated rat hepatocyte couplets. VP induced the concentration-dependent formation of multiple plasma membrane blebs as well as simultaneous impairment in both canalicular vacuolar accumulation (cVA) and retention (cVR) of the fluorescent bile acid, cholyl-lysyl-fluorescein (CLF), which evaluate couplet secretory function and tight-junction integrity, respectively. These effects were mimicked by the protein kinase C (PKC) activator, phorbol dibutyrate (PDB), but not by the protein kinase A (PKA) activator, dibutyryl-cAMP. VP-induced bleb formation and canalicular dysfunction were fully prevented by the protein kinase inhibitor, H-7, but not by the PKA inhibitor, KT5720, further suggesting a specific role of PKC. VP-induced alterations were also prevented by pretreatment with the Ca2+-buffering agent, BAPTA/AM, but not with the calmodulin-dependent protein kinase II antagonist, calmidazolium. Neither the Ca2+-activated neutral protease inhibitor, leupeptin, nor the antioxidants, alpha-tocopherol or deferoxamine, were able to prevent either VP-induced plasma membrane blebbing or canalicular dysfunction. The Ca2+-ionophore, A23187, mimicked the VP-induced alterations, but its harmful effects were completely prevented by H-7. Bleb formation induced by VP and PDB was accompanied by an extensive redistribution of filamentous actin from the pericanalicular area to the cell body, and this effect was fully prevented by H-7. These results suggest that VP-induced canalicular and cytoskeletal dysfunction is mediated by PKC and that classical (Ca2+-dependent) PKC appear to be involved because intracellular Ca2+ is required for VP to induce its harmful effects.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

Biologic pollution in infant bedding in New Zealand: high allergen exposure during a vulnerable period.

BACKGROUND: High exposure to house dust mite and cat allergens in early life predisposes to allergic sensitization and to the development and persistence of asthma. Prevalence and severity of asthma are high in New Zealand. OBJECTIVE: The objective of this study was to determine the concentrations of Der p 1 and Fel d 1 in infant bedding in Wellington, New Zealand. METHODS: Infants were visited at home at a mean age of 11 weeks and again at 15 months. The concentration (microgram/g fine dust) and content (microgram/m2) of Der p 1 (154 infants) and Fel d 1 (75 infants) were measured in dust samples taken from each infant's bed. RESULTS: At 11 weeks, geometric mean (95% confidence intervals) Der p 1 levels were 18.3 micrograms/g (13.8 to 24.1) and 3.51 micrograms/m2 (2.4 to 5.2). By 15 months, Der p 1 had risen significantly to 44.0 micrograms/g (35.0 to 55. 3) and 49.0 micrograms/m2 (36.0 to 66.8). Bedding that included a sheepskin was used by a third of the infants and contained higher concentrations (microgram/g) and content (microgram/m2) of Der p 1 than beds without sheepskins. Cat ownership was the major determinant of Fel d 1 levels, with 48% of infants living with cats. At the first visit, the mean concentration of Fel d 1 in bedding was 44.6 micrograms/g (23.5 to 84.9) for houses with cats and 3.0 micrograms/g (2.1 to 4.3) for those without cats, remaining essentially unchanged at the second visit. When expressed as micrograms per square meter, there was a significant increase between visits, from 8.1 (3.9 to 16. 6) to 39.6 (19.9 to 78.5) in the cat-inclusive households. CONCLUSIONS: Extremely high levels of house dust mite allergen have been found in these infants' environments, which, together with the high levels of cat allergen in almost half who kept cats, are likely to be a major determinant of asthma prevalence and severity in New Zealand.

Allergens↗
PubMed1998

Differences between African American and Caucasian men participating in a community-based prostate cancer screening program.

Prostate cancer is a major contributor to morbidity and mortality in the male population, but public awareness of the cancer has been reported as minimal. We evaluated the effectiveness of an educational prostate cancer screening program on 944 men in a midwest urban community. Digital rectal examinations and PSA blood tests were provided at no charge to participants with a grant from the Michigan Department of Community Health. An educational intervention that stressed the importance of prostate cancer early detection and treatment was conducted before screenings. A brief questionnaire administered before and after the videotape and screenings, targeted both knowledge and attitudes concerning prostate cancer. Pre-test results revealed that African American men were significantly (t = 3.7, P = .00) less likely then white men to correctly identify early symptoms of prostate cancer and the basic components of a prostate checkup. Following program involvement, scores significantly improved in all areas and differences were no longer significant between the races. Racial differences were also found for screening preferences and modes of reaching men to participate in screening. African American men were twice as likely as white men to choose private appointments over mass screening (OR = 2.2, P = .00). Radio reached the most African Americans (25%) while newspaper reached the most Caucasians (34%). The decreased level of knowledge among African Americans regarding prostate etiology and clinical factors highlights the need for educational programs to target minority populations. The need for discretion also applies by providing minority-favored access with screening through private appointments.

Adult↗
PubMed1997

Relation of operator volume and experience to procedural outcome of percutaneous coronary revascularization at hospitals with high interventional volumes.

BACKGROUND: Although an inverse relation between physician caseload and complications has been conclusively demonstrated for several surgical procedures, such data are lacking for percutaneous coronary intervention, and the ACC/AHA guidelines requiring > or = 75 cases per year for operator "competency" are considered by some physicians to be arbitrary. METHODS AND RESULTS: From quality-controlled databases at five high-volume centers, models predictive of death and the composite outcome of death, Q-wave infarction, or emergency bypass surgery were developed from 12,985 consecutively treated patients during 1993 through 1994. Models had moderate to high discriminative capacity (area under ROC curves, 0.65 to 0.85), were well calibrated, and were not overfitted by standard tests. These models were used for risk adjustment, and the relations between both yearly caseload and years of interventional experience and the two adverse outcome measures were explored for all 38 physicians with > or = 30 cases per year. The average physician performed a mean +/- SD of 163 +/- 24 cases per year and had been practicing angioplasty for 8 +/- 5 years. Risk-adjusted measures of both death and the composite adverse outcome were inversely related to the number of cases each operator performed annually but bore no relation to total years of experience. Both adverse outcomes were more closely related to the logarithm of caseload (for death, r = .37, P = .01; for death, Q-wave infarction, or bypass surgery, r = .58, P < .001) than to linear caseload. CONCLUSIONS: In this analysis, high-volume operators had a lower incidence of major complications than did lower-volume operators, but the difference was not consistent for all operators. If these data are validated, their implications for hospital, physician, and payer policy will require exploration.

Angioplasty, Balloon, Coronary↗
PubMed1997

Basic fibroblast growth factor prevents cAMP-induced apoptosis in cultured Schwann cells.

Peripheral nerve axotomy induces apoptosis in Schwann cell precursors; basic fibroblast growth factor (bFGF) protects these cells from axotomy-induced apoptosis (Jessen et al.: Neuron 12:509-527, 1994; Gavrilovic et al.: Eur J Neurosci 7:7-85, 1995). In this study, we investigate the effects of bFGF on apoptosis in neuron-free cultures of neonatal rat Schwann cells. Apoptotic cell death was induced in primary and secondary expanded Schwann cells by treatment with 1 mM concentrations of 8-bromoadenosine 3':5'-cyclic monophosphate (8-bromo-cAMP), a membrane-permeable analogue of cAMP which induces expression of galactocerebroside in the plasma membranes of Schwann cells. Treatment with bFGF reduced the percentage of galactocerebroside-bearing Schwann cells undergoing cAMP-induced DNA fragmentation. These findings suggest that bFGF can enhance the survival of terminally differentiated Schwann cells by preventing apoptosis.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1997

Progesterone levels on the day of human chorionic gonadotropin do not predict pregnancy outcome from the transfer of fresh or cryopreserved embryos from the same cohort.

OBJECTIVE: To analyze the differences in pregnancy rates (PRs) from the transfer of fresh and cryopreserved embryos from the same cohort of oocytes based on serum P levels on the day of hCG administration and the day after. DESIGN: Retrospective analysis. SETTING: Infertility patients stimulated for IVF-ET in an academic center. PATIENT(S): Three hundred thirty-three patients with fresh transfer and at least one transfer of cryopreserved embryos from the same cohort of recruited oocytes. All stimulations were down-regulated with a GnRH agonist in a long protocol before gonadotropin stimulation. MAIN OUTCOME MEASURE(S): Clinical PR. RESULT(S): The clinical PR in fresh cycles was 24% for the P < or = 0.9 ng/mL group (group A; conversion factor to SI unit, 3.18) and 34% for the P > 0.9 ng/mL group (group B). Group B patients were younger, received fewer ampules of gonadotropins, had higher peak E2 levels, and had more mature oocytes. There were no significant differences in the P levels on the day of hCG between patients who conceived in both fresh and cryopreserved cycles and any other combination of pregnancy outcome sequence. CONCLUSION(S): These findings suggest that serum P level cutoffs, on the day of hCG and the day after, as a means of making clinical decisions with respect to cancelling the fresh transfer and cryopreservation of all embryos for future transfer should be questioned.

Adult↗