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Biomedical subjects

A Shaw

Publications and source records attributed to A Shaw.

At least 73 records · Page 4Linked to original sources
PubMed1998

The Collaborative Randomised Amnioinfusion for Meconium Project (CRAMP): 1. South Africa.

OBJECTIVE: To evaluate transcervical amnioinfusion for meconium stained amniotic fluid during labout. DESIGN: Multicentre randomised controlled trial. SETTING: Four urban academic hospitals in South Africa. Obstetric surveillance included the use of electronic fetal heart rate monitoring in most cases. PARTICIPANTS: Women in labour at term with moderate or thick meconium staining of the amniotic fluid. INTERVENTIONS: Transcervical amnioinfusion of 800 mL saline at 15 mL per minute, followed by a maintenance infusion at 3 mL per minute. The control group received routine care. Blinding of the intervention was not possible. MAIN OUTCOME MEASURES: Caesarean section, meconium aspiration syndrome and perinatal mortality. RESULTS: Caesarean section rates were similar (amnioinfusion group 70/167 vs control group 68/159; RR 0.98, 95% CI 0.76-1.26). The incidence of meconium aspiration syndrome was lower than expected on the basis of previous studies (4/162 vs 6/163; RR 0.67, 95% CI 0.19-2.33). There were no perinatal deaths. There were no significant differences between any of the subsidiary outcomes. CONCLUSIONS: This study concurred with three previous trials which found no effect of amnioinfusion for meconium-stained amniotic fluid on caesarean section rate, though the pooled data from all identified trials to date show a significant reduction. The findings with respect to meconium aspiration syndrome were inconclusive in this study alone because of the small number of babies affected, but the point estimate of the relative risk was consistent with the finding of a significant reduction in previous studies and with the Zimbabwe arm (CRAMP 2) of this study. Pooled data clearly support the use of amnioinfusion for meconium stained amniotic fluid to reduce the incidence of meconium aspiration syndrome.

Amnion↗
PubMed1998

Can we trust the quality of routine hospital outpatient information in the UK? Validating outpatient data from the patient administration system (PAS).

BACKGROUND: A validation study of routine hospital outpatient data was carried out as part of a broader project focusing on outpatient re-attendance. The aim was to compare two patient administration system (PAS) data items with the same information collected directly from hospital clinicians. METHODS: A total of 140 cases from four specialties at four National Health Service hospitals was randomly selected for comparison. The specific data items compared were the grade of doctor seen and the management decision taken following an outpatient appointment. The proportion of cases in which there was agreement was calculated, together with kappa values and relevant statistics indicating the accuracy of the PAS data when compared with information compiled immediately after the consultation by the relevant clinician. RESULTS: There was agreement between the clinician's data and the PAS data in 118/140 (84.3%) cases for grade of doctor seen and in 105/139 (76.7%) cases for the management decision. There was complete agreement for both items in 88/139 (62.6%) cases. Kappa values indicated good agreement between the two data sources. However, 'sensitivity' statistics suggested that the likely accuracy of each data item varied. CONCLUSION: Although there was good agreement within individual categories between the two sources, 37% of patient computerised records held at least one inconsistency in this small study focusing on only two data items. Further systematic evaluation is needed to test the extent to which other items are similarly discrepant.

Data Collection↗
PubMed1998

Differential cell cycle checkpoint response in normal human keratinocytes and fibroblasts.

The incidence of DNA mutation and subsequent risk of transformation in different cell types may depend on cell type-specific variation in position and duration of cell cycle arrest after exposure to DNA-damaging agents. To determine whether cell type-specific checkpoints occur, normal human epidermal keratinocytes (HKs) and human dermal fibroblasts (HFs), isolated from the same tissue, were exposed to genotoxic agents. Following exposure, cell cycle arrest profiles, cell proliferation rates, and select protein levels and activities were analyzed and found to be cell type dependent. After exposure to either gamma-radiation or Adriamycin, HFs arrested primarily in G1, whereas HKs arrested predominantly in G2. The attenuated G1 arrest in the HKs correlated with less p53 protein accumulation, as compared to that observed in G1-arrested HFs. Although gamma-irradiated HFs were unable to reenter the cell cycle, HKs began proliferating 72 h posttreatment. Consistent with the cell cycle profiles observed, cyclin-dependent kinase activities were inhibited for a longer duration in HFs as compared to HKs after gamma-irradiation. The results indicate that cell cycle checkpoint response to genotoxic insult may vary according to cell type within any given tissue. The attenuated G1 arrest observed in HKs may be an important factor in the transforming events leading to skin neoplasia.

CDC2-CDC28 Kinases↗
PubMed1997

1,25-dihydroxyvitamin D3 regulates pp60c-src activity and expression of a pp60c-src activating phosphatase.

The nonreceptor tyrosine kinase, c-src, and the steroid hormone,1,25-dihydroxyvitamin D3(1,25(OH)2D3), are essential to development of the osteoclast phenotype. On the other hand, functional relationships between the activities of c-src and 1,25(OH)2D3 are as yet unknown. To determine if 1,25(OH)2D3 modulates c-src in osteoclastogenesis, we tested the steroid's effect on avian marrow-derived osteoclast precursors. We find c-src mRNA and immunoprecipitable c-src protein (pp60c-src) unaltered by 72 h exposure of these cells to 1,25(OH)2D3 (10(-11) to 10(-9) M). Despite no quantitative change in pp60c-src, in vitro kinase assay of the immune complex reveals 1,25(OH)2D3 dose-dependently accelerates the catalytic activity of pp60c-src, enhancing its autophosphorylation and phosphorylation of exogenous substrate. This observation represents the first documentation, in nontransformed cells, of humoral induction of pp60c-src kinase. Consistent with the fact pp60c-src is activated by dephosphorylation of tyrosine 527 (Y527), the phosphotyrosine content of the pp60c-src immunoprecipitate, measured by immunoblot, is decreased by 1,25(OH)2D3. Alternatively, mRNA and protein levels of c-src kinase (CSK), which inactivates pp60c-src by phosphorylating Y527, are not altered by the steroid. In contrast, 1,25(OH)2D3 enhances mRNA and especially protein levels of avian protein tyrosine phosphatase lambda (PTP lambda), an enzyme specifically activating pp60c-src by dephosphorylating Y527 [Fang et al. (1994): J Biol Chem 269:20194-20200]. Thus, treatment of avian osteoclast precursors with 1,25(OH)2D3 accelerates the catalytic activity of pp60c-src independent of protein expression. Activation of the kinase may occur via the Y527 dephosphorylating enzyme PTP, expression of which, we show for the first time, is regulated.

Animals↗
PubMed1997

Grip force scaling after hemispatial neglect.

Spatial neglect has been explained as an impairment in the representation of extrapersonal space. One account suggests that representations of extrapersonal space are spatially compressed following neglect. In support of this view it has been demonstrated that neglect patients systematically underestimate the size of stimuli presented in their left hemifield. In the current study we investigated this phenomena by obtaining an indirect measure of perceived object size - the scaling of grip force during prehension. We demonstrate for the first time that neglect patients show increased levels of grip force for objects presented in their left hemifield. This finding is discussed with reference to a proposed distinction between visual processing used for object recognition, and visual processing used to guide action.

Aged↗
PubMed1997

Orally active trifluoromethyl ketone inhibitors of human leukocyte elastase.

This paper describes the development a series of peptidyl trifluoromethyl ketone inhibitors of human leukocyte elastase which are found to have excellent pharmacological profiles. Methods have been developed that allow for the synthesis of these inhibitors in stereochemically pure form. Two of these compounds, 1k and 1l, have high levels of oral bioavailability in several species. Compound 1l has entered development as ZD8321 and is presently undergoing clinical evaluation. These compounds demonstrate that peptidyl trifluoromethyl ketone inhibitors can achieve high levels of oral activity and bioavailability, and therefore they may prove useful as therapeutic agents in the treatment of diseases in which elastase is implicated.

Administration, Oral↗
PubMed1997

Patients' perceptions of changes in their blood pressure.

OBJECTIVES: (1) To investigate patients' experience of changes in their blood pressure (BP) in an every day setting and the accuracy of patients' predictions; and (2) to examine what influences patients' belief that they can tell when their BP is up. SUBJECTS: A total of 102 hypertensive patients were recruited sequentially as they presented for routine BP checks. The setting was an inner city general practice. DESIGN: Patients attended for BP checks on a weekly basis. Before each check they were asked whether they thought their BP was higher, lower or the same as usual. Subjects were classified as predictors if they thought they could tell when their BP was up. On completing their series of BP checks each subject completed symptom and Hospital Anxiety and Depression questionnaires. MAIN OUTCOME MEASURES: Accuracy of BP predictions, BP levels and variability, number of symptoms reported and anxiety level. RESULTS: One hundred and two hypertensive patients entered the study of whom 51 patients were predictors. The majority (86%) of predictors could not accurately predict their BP. There were no significant differences in either BP or variability between predictors and non-predictors. Predictors were significantly more anxious and reported more symptoms than non-predictors. CONCLUSIONS: For the majority of predictors there is no significant relationship between predictions of BP and clinical measurements. Predictor status is associated with the reporting of more symptoms and higher levels of anxiety. Doctors should counsel patients against using subjective BP assessments to guide their use of antihypertensive medication.

Adult↗
PubMed1997

Analgesic effect of intra-articular bupivacaine or diamorphine after arthroscopic surgery of the knee joint in day-case patients.

A prospective, randomized, double-blind, controlled study was conducted to assess the efficacy of intra-articular bupivacaine and diamorphine. Ninety-six day-case patients were allocated randomly to receive intra-articular injections of either 20 mL 0.9% saline (control, n = 35), 20 mL 0.5% plain bupivacaine (n = 31), or 20 mL 0.9% saline with 5 mg diamorphine (n = 30) prior to tourniquet release. Visual analogue scales (VAS) were completed at 1 h, 3 h (discharge) and 24 h, and supplementary analgesia noted. Intra-articular analgesics conferred a noticeable improvement in patient comfort. First, the quantity of supplementary analgesia required prior to discharge was significantly reduced (P = 0.016); second, patients reported a less disturbed night's sleep (P = 0.034).

Adolescent↗
PubMed1997

Opportunities for optimizing resource utilization in ambulatory academic practices.

Growing emphasis on ambulatory service delivery in academic medical centers has heightened interest in improving operational efficiencies, while providing an optimal educational experience for medical students and residents. One significant challenge in the academic environment is maximizing resource utilization (both physical plant and personnel), through scheduling and operational effectiveness. This article examines how academic ambulatory practices can apply operational and scheduling process redesign methodologies to improve throughput and productivity, while enhancing the educational experience for students/residents.

Academic Medical Centers↗
PubMed1997

Inhibition of feline immunodeficiency virus infection by CD9 antibody operates after virus entry and is independent of virus tropism.

A monoclonal antibody which blocks infection with feline immunodeficiency virus (FIV) was found previously to react with the cell surface molecule CD9, implicating CD9 in the process of virus entry. We report here that inhibition by anti-CD9 antibody does not operate at the level of virus entry but at a subsequent stage in the virus life-cycle. Moreover, inhibition of infection is independent of the passage history of the virus or the virus subtype. Inhibition of FIV infection by anti-CD9 antibody does not operate in 3201 cells, which do not express this surface antigen. However, ectopic expression of CD9 on 3201 cells enhances infection with FIV, suggesting that the role of CD9 may be direct rather than via cellular signalling pathways. These results suggest a novel control point in the lentivirus life-cycle which might be susceptible to modulation by natural antagonists.

Animals↗
PubMed1997

Use of a fluorescent probe to assess the activities of candidate agents against intracellular forms of Encephalitozoon microsporidia.

Microsporidia are obligate intracellular protozoan parasites. Three species of the genus Encephalitozoon are among the microsporidia that infect immunodeficient humans. These species, Encephalitozoon cuniculi, Encephalitozoon hellem, and Encephalitozoon intestinalis, all develop in a parasitophorous vacuole within a host cell. The present study describes a method that uses the fluorescent probe calcein and confocal microscopy to detect drug-induced effects in Encephalitozoon-infected green monkey kidney cells. The effects were as follows: (i) changes in parasite organization within the parasitophorous vacuole; (ii) swelling and gross morphological changes of parasite developing stages in situ; (iii) killing of developing parasite stages in situ, detected by their uptake of the fluorescent probe; and (iv) reduction in the viability of the host cell population, assessed by the loss of the probe. Verapamil and itraconazole were used to increase the vital dye loading by both uninfected and infected cells. Agents with known antimicrosporidial activity, albendazole and fumagillin, caused all three types of parasite changes at concentrations that had no detectable effect on host cell viability. The effective doses of albendazole and fumagillin that caused swelling and disorganization of parasite developing stages were 5 x 10(-7) and 10(-6) M respectively. Killing of developing stages was detected at 10-fold-higher concentrations for these agents and at 10(-5) M for metronidazole. This method can be used to screen candidate antimicrosporidial agents in infected cultured cells.

Albendazole↗
PubMed1996

ATP-citrate lyase as a target for hypolipidemic intervention. Design and synthesis of 2-substituted butanedioic acids as novel, potent inhibitors of the enzyme.

ATP-citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. Inhibitors of the enzyme represent a potentially novel class of hypolipidemic agent, which are anticipated to have combined hypocholesterolemic and hypotriglyceridemic properties. A series of 2-substituted butanedioic acids have been designed and synthesized as inhibitors of the enzyme. The best compounds, 58, 68, 71, 74 have reversible Ki's in the 1-3 microM range against the isolated rat enzyme. As representative of this compound class, 58, has been shown to exert its inhibitory action through a mainly competitive mechanism with respect to citrate and a noncompetitive one with respect to CoA. None of the inhibitors were able to inhibit cholesterol and/or fatty acid synthesis in HepG2 cells. This has been attributed to the adverse physicochemical properties of the molecules leading to a lack of cell penetration. Despite this, a lead structural class of compound has been identified with the potential for modification into potent, cell-penetrant, and efficacious inhibitors of ATP-citrate lyase.

ATP Citrate (pro-S)-Lyase↗