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Biomedical subjects

A Grant

Publications and source records attributed to A Grant.

At least 91 records · Page 5Linked to original sources
PubMed1998

Characteristics of L-carnitine transport by lactating rat mammary tissue.

The transport of L-carnitine by lactating rat mammary tissue has been examined. L-carnitine uptake by rat mammary tissue explants isolated from lactating rats, 3-4 days post partum, was via both Na+-dependent and Na+-independent pathways. The Na+-dependent pathway, the predominant route for L-carnitine uptake, was a saturable process: the Km and Vmax were, respectively, 132 microM and 201 pmol/2 h/mg of intracellular water. The Na+-independent pathway, which was non-saturable, had a coefficient of 0.26 microl/mg of intracellular water/2 h. The Na+-dependent component of L-carnitine uptake by mammary tissue explants was cis-inhibited by D-carnitine and acetyl-L-carnitine, but not by choline or taurine. In contrast, the Na+-independent component of L-carnitine uptake was not affected by any of these compounds. The uptake of L-carnitine by mammary tissue isolated from lactating rats, 10-12 days post partum, was qualitatively similar to that by mammary tissue taken from rats during the early stage of lactation. However, L-carnitine uptake was quantitatively lower: this was attributable to a reduction in the Na+-dependent component of L-carnitine uptake. L-Carnitine efflux from rat mammary tissue taken from animals 3-4 days post partum, consisted of at least two components; a fast extracellular component and a slow membrane-limited component. Reversing the trans-membrane Na+-gradient did not stimulate L-carnitine efflux suggesting that the Na+-dependent L-carnitine carrier operates with asymmetrical kinetics. A hyposmotic shock, hence cell-swelling, increased L-carnitine efflux from mammary tissue explants.

Animals↗
PubMed1998

Measurement of autolysis in submerged batch cultures of Penicillium chrysogenum.

The process of cellular autolysis was studied in an industrial strain of Penicillium chrysogenum by a range of methods, including assessment of biomass decline, NH+4 release, changes in culture apparent viscosity, and by means of a quantitative assessment of changes in micromorphology using a computerized image analysis system. The pattern of total intracellular proteolytic and beta-1, 3-glucanolytic activity in the culture was also examined. The overall aim was to identify a suitable method, or methods, for examining the extent of autolysis in fungal cultures. Autolysis was studied in submerged batch processes, where DOT was maintained above 40% saturation (non-O2-limited), and, under O2-limited conditions. Both N and O2 limitation promoted extensive culture autolysis. Image analysis techniques were perhaps the most sensitive method of assessing the progress of autolysis in the culture. Autolytic regions within some hyphae were apparent even during growth phase, but became much more widespread as the process proceeded. The early stages of autolysis involved continued energy source consumption, increased carbon dioxide evolution rate, degradation of penicillin, and decreased broth filterability. Later stages involved widespread mycelial fragmentation, with some regrowth (cryptic growth) occurring in non-O2-limited cultures. Intracellular proteolytic activity showed two peaks, one during the growth phase, and the other during autolysis. Autolysis was also associated with a distinct peak in beta-1,3-glucanolytic activity, indicating that degradation of cell wall matrix polymers may be occurring during autolysis in this strain of P. chrysogenum.

Biomass↗
PubMed1998

Magnetic resonance imaging for the investigation of knee injuries: an investigation of preferences.

The conventional approach to the diagnosis and treatment of severe knee injuries is arthroscopy, a minimally invasive surgical procedure. Since arthroscopy is an invasive technique that carries risks, magnetic resonance imaging (MRI) is increasingly being used for diagnosis. MRI is potentially associated with diagnostic and therapeutic 'impacts', in that arthroscopy can be avoided. This paper reports a discrete choice conjoint analysis exercise that assessed the value placed on such 'impacts' by potential patients and investigated the degree to which respondents were willing to trade between process and outcome. The marginal rates of substitution between attributes were estimated. The results suggest that the diagnostic and therapeutic 'impacts' of MRI were valued by many respondents. The study has highlighted a number of important issues for the design and analysis of future health-related conjoint studies, including the use of treatment cost as an attribute, dealing with data from lexicographic respondents, and distinguishing between points of indifference and missing data.

Adult↗
PubMed1998

Analytical evaluation of the testosterone assay on the Bayer Immuno 1 system.

OBJECTIVES: To evaluate the analytical performance of the testosterone assay performed on the Bayer immuno 1 system from Bayer Corporation. DESIGN AND METHODS: The precision was measured using three Bayer TESTpoint Ligand controls, three Medical Decision Pools and the Bayer SETpoint Testosterone calibrators. The linearity was verified by diluting two serum samples containing high testosterone concentrations with the zero calibrator and the minimum detectable concentration determined by repetitive analysis of the zero calibrator. The assay was correlated with the Diagnostic Products Corporation (DPC) Total Testosterone assay using 342 serum samples. The reference values were determined using serum samples from 75 women and 60 men. RESULTS: The assay showed within-run coefficients of variation (CVs) varying from 1.1-8.4% and between-day CVs from 1.5-4.9% for testosterone concentrations varying from 1.77 to 66.96 nmol/L. The minimum detectable concentration was estimated at 0.11 nmol/L. The assay linearity proved excellent. A good correlation between the Bayer Immuno 1 and the DPC assays was observed with different categories of serum samples (Immuno 1 = 1.11 x DPC-0.32, r = 0.989, Sy[symbol: see text]x = 2.07 nmol/L). The reference values were estimated at 0.3-3.2 nmol/L for females and 9.3-35.6 nmol/L for males. CONCLUSIONS: The Bayer Immuno 1 Testosterone assay demonstrates the analytical characteristics required for its utilization in the clinical laboratory.

Adult↗
PubMed1998

A new form of complicated hereditary spastic paraplegia with cataracts, atretic ear canals and hypopigmentation.

A 16-year-old Hispanic boy born of consanguineous parents is described as having a history of cataracts, progressive lower-extremity spasticity and atrophy starting at 4 years of age, atretic ear canals with hearing dysfunction and diffuse patchy cutaneous hypopigmented areas. Clinical examination showed the typical signs of spastic paraplegia with increased tone, hyperreflexia, muscle atrophy and contractures. Sensation, autonomic and cerebellar functions were not disturbed. Neuroimaging studies were normal. Laboratory findings did not support a diagnosis of metabolic disturbance or infectious disease. This is considered a new form of complicated hereditary spastic paraplegia (HSP), transmitted presumably in an autosomal recessive pattern.

Adolescent↗
PubMed1998

Implementing early warning messages on emerging health technologies.

The purpose of this study was to determine how horizon-scanning organizations can encourage the implementation of recommendations contained in their early warning messages about emerging health technologies. We reviewed the conclusions of the EUR-ASSESS Project Subgroup report on dissemination and impact, an overview of systematic reviews of interventions to promote implementation of research findings by health care professionals, and various Cochrane Effective Practice and Organisation of Care Group protocols and reviews. The evidence on the effectiveness of different implementation strategies aimed at distinct target groups is of variable quality. There is some evidence from rigorous study designs on the effectiveness of strategies designed to influence the behavior of health care professionals; the quality of the evidence relating to policy makers and the general public is more limited. Horizon-scanning organizations can improve the likelihood of their recommendations being acted upon by developing active implementation strategies based on the best available evidence, establishing links with key groups, and directing early warning messages at specific target audiences. Given the relative lack of good quality evidence, it is important that implementation strategies be rigorously evaluated to determine their effectiveness.

Diffusion of Innovation↗
PubMed1998

Evaluation of a programme of workshops for promoting the teaching of critical appraisal skills.

The aim of this study was to assess the effectiveness of four training workshops at the inception of a programme to cascade critical appraisal skills training throughout Scotland. Data were collected from all participants and organizers at four commissioned critical appraisal skills training workshops in Scotland. The collection of data involved three components: a survey of workshop participants before and after each workshop to determine knowledge of the principles of clinical effectiveness; semi-structured interviews with organizers before, during and after the programme of commissioned workshops to assess views on the workshops; and a postal survey to determine involvement in critical appraisal activities following the initial workshops. The main outcome measures were 'change in knowledge' and subsequent involvement in teaching. An average of 41 people attended each workshop. Participants improved their scores on understanding of clinical effectiveness. Not all of the improvement can be ascribed to the workshops, however, because control item scores also improved, albeit to a lesser extent. The workshops were perceived as an acceptable way of acquiring critical appraisal skills, but doubts were expressed about whether participants would be able to roll out the programme on their own. Of the 32 (42%) attendees who were involved in CASP-style workshops after the initial workshops, 26 (34%) providing aspects of teaching, and a further six (8%) were participants. The evaluation of the CASP workshop technique suggests that it does improve knowledge of clinical effectiveness, but concerns remain about the viability and reliability of this approach as it rolls out training within Scotland.

Education, Medical, Continuing↗
PubMed1998

BipA: a tyrosine-phosphorylated GTPase that mediates interactions between enteropathogenic Escherichia coli (EPEC) and epithelial cells.

We report the functional characterization of BipA, a GTPase that undergoes tyrosine phosphorylation in an enteropathogenic Escherichia coli (EPEC) strain. BipA mutants adhere to cultured epithelial cells but fail to trigger the characteristic cytoskeletal rearrangements found in cells infected with wild-type EPEC. In contrast, increased expression of BipA enhances actin remodelling and results in the hyperformation of pseudopods. BipA appears to be the first example of a new class of virulence regulator, as it also controls flagella-mediated cell motility and resistance to the antibacterial effects of a human host defence protein. Its striking sequence similarity to ribosome-binding elongation factors suggests that it uses a novel mechanism to modulate gene expression.

Amino Acid Sequence↗
PubMed1998

Intra-umbilical vein injection and retained placenta: evidence from a collaborative large randomised controlled trial. Grupo Argentino de Estudio de Placenta Retenida.

OBJECTIVE: To determine whether intra-umbilical vein injection with saline solution, with or without oxytocin, reduces the need for manual removal of placenta compared with expectant management. DESIGN: Multicenter, randomised controlled trial. SETTING: Eleven hospitals in four cities of Argentina: Buenos Aires, Corrientes, Rosario, and Salta. PARTICIPANTS: Two hundred and ninety-one women showing no evidence of placental separation thirty minutes after vaginal delivery. INTERVENTIONS: Three different management strategies: 1. intra-umbilical vein injection of saline solution plus oxytocin; 2. intra-umbilical vein injection of saline solution alone; and 3. expectant management. MAIN OUTCOME MEASURES: Primary: manual removal of the placenta. Secondary: blood loss after trial entry, haemoglobin level at 24 to 48 hours and at 40 to 45 days after delivery, blood transfusion, curettage, infection, and days of hospital stay. RESULTS: Rates of subsequent manual removal were similar: intra-umbilical vein injection of saline solution plus oxytocin (58%; RR 0.92; 95% CI 0.73-1.15), or saline alone (63%; RR 1.00; 95% CI 0.80-1.24), compared with expectant management (63%). There were also no detectable effects of the active managements on any of the secondary measures of outcome. CONCLUSIONS: Based on evidence available from randomised controlled trials, including this trial, it is unlikely that intra-umbilical injection with or without oxytocin, is clinically useful. We recommend that this intervention should not be used in third stage management of labour.

Female↗
PubMed1998

Barbados Low Dose Aspirin Study in Pregnancy (BLASP): a randomised trial for the prevention of pre-eclampsia and its complications.

OBJECTIVE: To determine whether prophylactic, low dose controlled-release aspirin improves outcome for pregnant women and their babies in Barbados. DESIGN: Randomised placebo-controlled trial. SETTING: The Queen Elizabeth Hospital, Barbados. POPULATION: All women attending antenatal clinics between 12 and 32 weeks of gestation were eligible, if without specific contraindications to aspirin and unlikely to deliver immediately. METHODS: Randomisation was computer-generated in the antenatal clinic; 1822 women were allocated to receive 75 mg controlled-release aspirin and 1825 matching placebo. MAIN OUTCOME MEASURES: Proteinuric pre-eclampsia, other pregnancy-induced hypertension, pregnancy duration, birthweight, stillbirths and neonatal deaths, major neonatal events. RESULTS: All but three women from each group were followed up successfully. Forty-four percent were primigravid, and 8% had previous obstetric complications. There were no significant differences between the allocated treatment groups in the incidence of proteinuric pre-eclampsia (40 [2.2%] of those allocated aspirin, compared with 46 [2.5%] allocated placebo), of preterm delivery (255 [14.0%] vs 270 [14.8%]), of birthweight < 1500 g (32 [1.7%] vs 33 [1.8%]) or of stillbirth and neonatal death (44 [2.4%] vs 38 [2.1%]). Aspirin was not associated with excess risk of maternal or fetal bleeding. CONCLUSIONS: The results of this study in Barbados do not support the routine use of low dose aspirin for prevention of pre-eclampsia or its complications, confirming results of previous large trials in other settings.

Adult↗
PubMed1998

The Ipswich Childbirth Study: 1. A randomised evaluation of two stage postpartum perineal repair leaving the skin unsutured.

OBJECTIVE: To evaluate a policy of two stage postpartum perineal repair leaving the skin unsutured. DESIGN: A stratified randomised controlled trial using a 2 x 2 factorial design. SETTING: The maternity unit at Ipswich Hospital NHS Trust, a district general hospital, between 1992 and 1994. SAMPLE: 1780 women requiring surgical repair of episiotomy or first or second degree tear following a spontaneous or simple instrumental delivery. METHODS: A policy of two-stage perineal repair leaving skin unsutured was compared with a policy of three stage repair including skin closure with interrupted or subcuticular sutures. Both groups were assessed by a research midwife, blind to the allocation, completing questionnaires at 24 to 48 hours and 10 days postpartum, and by self-completed questionnaires at three months after birth. MAIN OUTCOME MEASURES: 1. 24 to 48 hours postpartum: perineal pain; healing; 2. 10 days postpartum: perineal pain, healing and removal of sutures; 3. three months postpartum: perineal pain, removal of sutures, resuturing, dyspareunia, and failure to resume pain-free intercourse. RESULTS: Completed questionnaires were returned for 99% of women at both 24 to 48 hours and ten days and by 93% of women three months postpartum. No differences were detected in perineal pain at 24 to 48 hours (62% vs 64%; RR 0.96, 95% CI 0.90-1.03; 2P = 0.3) and 10 days (25% vs 28%; RR 0.90, 95% CI 0.77-1.06; 2P = 0.2). Significantly fewer women allocated to two-stage repair reported tight stitches at ten days (14% vs 18%; RR 0.77, 95% CI 0.62-0.96, 2P = 0.02); similar numbers of repairs were judged to be breaking down (five compared with seven women). At three months postpartum fewer women allocated to the two-stage repair reported perineal pain and more had resumed pain-free intercourse. Amongst women who had resumed intercourse there was a significant difference in dyspareunia (15% vs 19%; RR 0.80, 95% CI 0.65-0.99; 2P = 0.04). Significantly fewer women in the two-stage repair group (7% vs 12%; RR 0.61, 95% CI 0.45-0.83; 2P = < 0.01) reported removal of suture material. Four women in the two-stage repair group had required resuturing, compared with nine allocated to the three-stage repair. CONCLUSIONS: Two-stage repair of perineal trauma leaving the skin unsutured appears to reduce pain and dyspareunia three months postpartum. There are no apparent disadvantages, in particular no evidence of an increased risk of breakdown of the repair and resuturing.

Adult↗
PubMed1998

The Ipswich Childbirth Study: 2. A randomised comparison of polyglactin 910 with chromic catgut for postpartum perineal repair.

OBJECTIVE: To compare polyglactin 910 sutures with chromic catgut sutures for postpartum perineal repair. DESIGN: A stratified randomised controlled trial, using a 2 x 2 factorial design. SETTING: The maternity unit at Ipswich Hospital NHS Trust, a district general hospital, between 1992 and 1994. SAMPLE: 1780 women who had sustained an episiotomy or first or second degree tear following a spontaneous or simple instrumental delivery. METHODS: Policies of repair with polyglactin 910 or chromic catgut were compared. Both groups were assessed by a research midwife completing questionnaires at 24 to 48 hours and at ten days postpartum, and by self-completed questionnaires at three months after birth. MAIN OUTCOME MEASURES: 1. 24 to 48 hours postpartum: perineal pain, healing; 2. ten days postpartum: perineal pain, healing and removal of sutures; 3. three months postpartum: perineal pain, removal of sutures, resuturing, dyspareunia, and failure to resume pain-free intercourse. RESULTS: Completed questionnaires were returned for 99% of women at both 24 to 48 hours and ten days and by 93% of women three months postpartum. The two groups were similar at trial entry. Significantly fewer women allocated to the polyglactin 910 reported pain in the previous 24 hours at both 24 to 48 hours (59% vs 67%; RR 0.89, 95% CI 0.83-0.95; 2P < 0.01), and ten days (24% vs 29%; RR 0.81, 95% CI 0.69-0.95; 2P = 0.01). At three months postpartum there was no clear difference between the groups in terms of perineal pain, dyspareunia or failure to resume pain-free intercourse. More women in the polyglactin 910 group reported that some suture material had been removed (12% vs 7%; RR 1.62, 95% CI 1.19-2.21; 2P < 0.01). Three women in the polyglactin 910 group had required resuturing compared with ten in the chromic catgut group (RR 0.30; 95% CI 0.08-1.09; 2P = 0.1). CONCLUSIONS: Using polyglactin 910 rather than chromic catgut for perineal repair leads to about one fewer women among every 20 having perineal pain and using analgesia ten days postpartum. Its only apparent disadvantage is that more women, again estimated as 1 in 20, report having material removed during healing. Data from this and other trials suggest that for every 100 women repaired with a polyglycolic acid-based material, about one fewer will require resuturing.

Adult↗
PubMed1998

Development of a scheme for genotyping Helicobacter pylori based on allelic variation in urease subunit genes.

Helicobacter pylori urease subunit genes in 383 isolates from 10 countries were investigated by PCR-restriction fragment length polymorphism (HaeIII) analysis. Eighty-two different ureAB profiles were documented by reference to known sequences. Variation among 51% of strains was accounted for by 10 predominant patterns, which provided a unique framework for categorizing isolates with geographically diverse origins.

Alleles↗
PubMed1998

The xenoestrogen bisphenol A induces growth, differentiation, and c-fos gene expression in the female reproductive tract.

The xenoestrogen bisphenol A (BPA) has been shown to mimic estrogen both in vivo and in vitro. BPA stimulates PRL secretion and the expression of a PRL regulating factor from the posterior pituitary in the estrogen-sensitive Fischer 344 rat (F344), but not in Sprague-Dawley (SD) rats. The goal of the present studies was to examine the in vivo actions of BPA on the reproductive tract. The specific objectives were 1) to characterize the short term effects of BPA on cell proliferation and c-fos expression in the uterus and vagina, and 2) to compare the effects of prolonged exposure to low doses of BPA on the reproductive tract of F344 and SD rats. Treatment with single high doses of BPA induced cell proliferation in the uterus and vagina of ovariectomized F344 rats, as determined by bromodeoxyuridine immunostaining. This proliferation was dose dependent (from 37.5-150 mg/kg) and followed a time course similar to that of estradiol (E2). Quantitative RT-PCR revealed that both BPA and E2 increased c-fos messenger RNA levels in the uterus 14- to 16-fold within 2 h, which returned to basal levels after 6 h. In the vagina, BPA-induced c-fos expression remained elevated for up to 6 h, compared with the transient increase caused by E2. Treatment of F344 rats for 3 days with continuous release capsules that supplied a much lower dose of BPA (approximately 0.3 mg/kg x day) resulted in hypertrophy, hyperplasia, and mucus secretion in the uterus and hyperplasia and cornification of the vaginal epithelium. The reproductive tract of SD rats did not respond to this treatment paradigm with BPA. These studies demonstrate that 1) the molecular and morphological alterations induced by BPA in the uterus and vagina are nearly identical to those induced by estradiol; 2) the vagina appears to be especially sensitive to the estrogenic actions of BPA; 3) the reproductive tract of the inbred F344 rat appears more sensitive to BPA than that of the outbred SD rat; and 4) continuous exposure to microgram levels of BPA is sufficient for exerting estrogenic actions.

Animals↗