Search PubMed⌕ Search

Biomedical subjects

E Murray

Publications and source records attributed to E Murray.

At least 37 records · Page 2Linked to original sources
PubMed1999

Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer.

PURPOSE: This phase III study compared docetaxel and doxorubicin in patients with metastatic breast cancer who had received previous alkylating agent-containing chemotherapy. PATIENTS AND METHODS: Patients were randomized to receive an intravenous infusion of docetaxel 100 mg/m(2) or doxorubicin 75 mg/m(2) every 3 weeks for a maximum of seven treatment cycles. RESULTS: A total of 326 patients were randomized, 165 to receive doxorubicin and 161 to receive docetaxel. Overall, docetaxel produced a significantly higher rate of objective response than did doxorubicin (47.8% v 33.3%; P =.008). Docetaxel was also significantly more active than doxorubicin in patients with negative prognostic factors, such as visceral metastases (objective response, 46% v 29%) and resistance to prior chemotherapy (47% v 25%). Median time to progression was longer in the docetaxel group (26 weeks v 21 weeks; difference not significant). Median overall survival was similar in the two groups (docetaxel, 15 months; doxorubicin, 14 months). There was one death due to infection in each group, and an additional four deaths due to cardiotoxicity in the doxorubicin group. Although neutropenia was similar in both groups, febrile neutropenia and severe infection occurred more frequently in the doxorubicin group. For severe nonhematologic toxicity, the incidences of cardiac toxicity, nausea, vomiting, and stomatitis were higher among patients receiving doxorubicin, whereas diarrhea, neuropathy, fluid retention, and skin and nail changes were higher among patients receiving docetaxel. CONCLUSION: The observed differences in activity and toxicity profiles provide a basis for therapy choice and confirms the rationale for combination studies in early breast cancer.

Adult↗
PubMed1999

Adenocarcinoma of the uterine cervix in Ireland and Sweden: human papillomavirus infection and biologic alterations.

Paraffin-embedded samples from cervical adenocarcinomas, 19 cases from Irish patients and 19 cases from Swedish patients, were analyzed by polymerase chain reaction for the presence of infection with human papillomavirus (HPV). The results were compared with DNA ploidy, proliferation activity, and p53 and p21/WAF1 expression. The studies were performed to discover whether high-risk HPV infection in adenocarcinomas of the uterine cervix is associated with an increased proliferative activity and genomic instability. The results show that the majority (84.6%) of patients 59 years of age or younger showed HPV infection. The overall prevalence of HPV DNA was 60.5%, with the high-risk types, 16 and 18, the most frequent. HPV-16 had a prevalence of 23.7% (9 of 38), and HPV-18 had a prevalence of 26.3% (10 of 38). The HPV-positive tumors predominantly showed a tetraploid DNA distribution pattern, whereas HPV-negative tumors more frequently showed highly scattered aneuploid DNA profiles. Both HPV-positive and HPV-negative cases displayed high proliferative activity, as indicated by high Ki-67 and cyclin A immunoreactivity. Tumor suppressor gene analysis detected low p53 expression and high p21/WAF1 expression in HPV-positive patients and high p53 expression without simultaneously increased p21/WAF1 (indicative of mutated p53) in HPV-negative cases in the groups of women older than 59 years of age.

Adenocarcinoma↗
PubMed1999

Community-based teaching: the challenges.

The amount of undergraduate medical education delivered in general practice is expanding rapidly, both in the United Kingdom and internationally. There are a number of challenges facing general practice as well as medical schools, health authorities and primary care groups, which must be met for this development to be sustainable. These include: impact on service general practice; resources; difficulties with integrating basic sciences with clinical teaching; recruitment, training and maintenance of GP tutors; quality control; impact on academic departments of primary care; and the importance of rigorous evaluation of educational initiatives. Possible solutions are discussed, such as development of university linked practices and the move toward a culture of 'evidence-based education', where all medical education is scrutinized for effectiveness.

Burnout, Professional↗
PubMed1998

Assessment of particle size distributions of health-relevant aerosol exposures of primary lead smelter workers.

Experiments were conducted at a primary lead smelter to investigate the particle size distributions of lead-containing aerosol to which workers were exposed, using personal inhalable dust spectrometers (PIDS) in specific smelter process areas. A total of 46 PIDS samples were evaluated, taken from the ore storage/mill, sinter plant, blast furnace and dross furnace process areas. Continuous particle size distributions were derived from the raw PIDS data employing a recently-developed optimisation routine, enabling determination of the percentages of inhalable, thoracic and respirable aerosol (in terms of lead content) as fractions of total lead aerosol. In addition, the mass ratios thoracic/inhalable and respirable/inhalable were also determined. Although the parameters of the measured particle size distributions ranged widely, some clear trends emerged. Firstly, the aerosols were coarser than had been expected based on measurements of previously reported workplace particle size distributions. This is thought to be due to the fact that the PIDS collects larger particles more efficiently than other instruments which have been used for such measurements. Secondly, there were significant differences in particle size distribution between process areas, in particular that the aerosol in the blast furnace area was generally finer than in the sinter plant. Such results may be used to support the results of workplace studies (reported elsewhere) into the differences between exposures to inhalable and 'total' aerosol as measured using different sampling instruments, especially when they are used together with knowledge of the physical processes governing the performances of such instruments.

Analysis of Variance↗
PubMed1998

Sequence analysis of the GntII (subsidiary) system for gluconate metabolism reveals a novel pathway for L-idonic acid catabolism in Escherichia coli.

The presence of two systems in Escherichia coli for gluconate transport and phosphorylation is puzzling. The main system, GntI, is well characterized, while the subsidiary system, GntII, is poorly understood. Genomic sequence analysis of the region known to contain genes of the GntII system led to a hypothesis which was tested biochemically and confirmed: the GntII system encodes a pathway for catabolism of L-idonic acid in which D-gluconate is an intermediate. The genes have been named accordingly: the idnK gene, encoding a thermosensitive gluconate kinase, is monocistronic and transcribed divergently from the idnD-idnO-idnT-idnR operon, which encodes L-idonate 5-dehydrogenase, 5-keto-D-gluconate 5-reductase, an L-idonate transporter, and an L-idonate regulatory protein, respectively. The metabolic sequence is as follows: IdnT allows uptake of L-idonate; IdnD catalyzes a reversible oxidation of L-idonate to form 5-ketogluconate; IdnO catalyzes a reversible reduction of 5-ketogluconate to form D-gluconate; IdnK catalyzes an ATP-dependent phosphorylation of D-gluconate to form 6-phosphogluconate, which is metabolized further via the Entner-Doudoroff pathway; and IdnR appears to act as a positive regulator of the IdnR regulon, with L-idonate or 5-ketogluconate serving as the true inducer of the pathway. The L-idonate 5-dehydrogenase and 5-keto-D-gluconate 5-reductase reactions were characterized both chemically and biochemically by using crude cell extracts, and it was firmly established that these two enzymes allow for the redox-coupled interconversion of L-idonate and D-gluconate via the intermediate 5-ketogluconate. E. coli K-12 strains are able to utilize L-idonate as the sole carbon and energy source, and as predicted, the ability of idnD, idnK, idnR, and edd mutants to grow on L-idonate is altered.

Biological Transport↗
PubMed1997

Can students learn clinical method in general practice? A randomised crossover trial based on objective structured clinical examinations.

OBJECTIVE: To determine whether students acquired clinical skills as well in general practice as in hospital and whether there was any difference in the acquisition of specific skills in the two environments. DESIGN: Randomised crossover trial. SUBJECTS AND SETTING: Annual intake of first year clinical students at one medical school. INTERVENTION: A 10 week block of general internal medicine, one half taught in general practice, the other in hospital. Students started at random in one location and crossed over after five weeks. OUTCOME MEASURES: Students' performance in two equivalent nine station objective structured clinical examinations administered at the mid and end points of the block: a direct comparison of the two groups' performance at five weeks; analysis of covariance, using their first examination scores as a covariate, to determine students' relative improvement over the second five weeks of their attachment. RESULTS: 225 students rotated through the block; all took at least one examination and 208 (92%) took both. For the first half of the year there was no significant difference in the students' acquisition of clinical skills in the two environments; later, however, students taught in general practice improved slightly more than those taught in hospital (P = 0.007). CONCLUSIONS: Students can learn clinical skills as well in general practice as in hospital; more work is needed to clarify where specific skills, knowledge, and attitudes are best learnt to allow rational planning of the undergraduate curriculum.

Clinical Competence↗
PubMed1997

Comparison of two methods of screening for genital chlamydial infection in women attending in general practice: cross sectional survey.

OBJECTIVES: To estimate the prevalence of Chlamydia trachomatis in asymptomatic women attending general practice: to assess the potential of the ligase chain reaction as a screening tool; and to evaluate selective screening criteria. DESIGN: Cross sectional survey. SETTING: Four general practices in northeast London. SUBJECTS: 890 women aged 18-35 years attending general practice for a cervical smear or a "young well woman" check between October 1994 and January 1996. The women were tested for C trachomatis with confirmed enzyme immunoassay (endocervical specimens) and ligase chain reaction assay on urine specimens. MAIN OUTCOME MEASURES: Prevalence of C trachomatis infection in women aged 18-35 on the basis of each test; sensitivity and specificity of both tests in this population. RESULTS: Prevalence of confirmed infection was 2.6% (95% confidence interval 1.6% to 3.6%) in all women. Prevalence on the basis of enzyme immunoassay was 1.6% (0.8% to 2.7%), with a sensitivity of 60% and a specificity of 100%. Prevalence on the basis of ligase chain reaction was 2.5% (1.5% to 3.9%), with 90% sensitivity and 99.8% specificity. Screening all women aged < or = 25 and all women who had had two or more partners in the past year would have detected 87% (20/23) of infections. CONCLUSION: Ligase chain reaction on urine samples performs at least as well as enzyme immunoassay on cervical specimens in this low prevalence population. It offers potential as a non-invasive screening tool. A simple selective screening strategy might be appropriate and would be able to detect most cases of infection. However, a rigorous economic evaluation of possible screening strategies is needed first.

Adult↗
PubMed1997

Characterization of a novel transporter family that includes multiple Escherichia coli gluconate transporters and their homologues.

The nucleotide sequences of seven Escherichia coli genes that encode members of the gluconate permease (GntP) family have recently become available. These genes include gntP, gntU, gntW, ORf449, dsdX, and ORFo454. The deduced amino acid sequences of all seven E. coli genes are homologous to the gntP gene products from Bacillus subtilis and B. licheniformis as well as two additional gene products from Haemophilus influenzae. These 11 proteins are not demonstrably homologous to members of the major facilitator superfamily or other recognized permease families. Four of the E. coli gluconate transporter genes have been cloned and shown to encode gluconate transporters with apparent affinities ranging from 6 to 212 microM. These studies serve to characterize a novel family of bacterial permeases.

Bacillus↗
PubMed1997

Can general internal medicine be taught in general practice? An evaluation of the University College London model.

There is national and international interest in increasing the community-based component of undergraduate medical education, but more research is needed on its potential, practicability and effectiveness. The objective of the study was to examine the feasibility and efficacy of general practitioners teaching basic clinical skills to first year clinical medical students in the community. The structure and methods of evaluation of the programme are described. Evaluation tools included semistructured interviews of general practitioner tutors; student questionnaires; assessment of student performance; and costs of the programme. The great majority of the students found the programme enjoyable (81 out of 81, 100%) and educational (79 out of 81, 97%). Students' performance in the end of rotation Objective Structured Clinical Examination suggested that clinical skills are acquired at least as well in the community as in the hospital. Tutors identified the personal benefits of this teaching as development of their own clinical skills and the stimulation of teaching. The programme has been successfully expanded from 24 students to 230 students annually and has demonstrated that community-based teaching can usefully contribute to undergraduate medical education in the area of clinical skills teaching. Key practical issues for schools contemplating similar initiatives are presented.

Adult↗
PubMed1997

Pulsatile and nonpulsatile extracorporeal circulation using Capiox E terumo oxygenator: a comparison study with Ultrox and Maxima membrane oxygenators.

An open randomised, prospective study was undertaken on 90 patients who underwent routine myocardial revascularization. The aim of the study was to demonstrate that the Capiox E polypropylene fiber membrane oxygenator with a conventional single pulsatile/nonpulsatile blood pump for cardiopulmonary bypass (CPB) was comparable in performance to that of the Maxima and the Ultrox membrane oxygenators using a double pump system. The patients were divided into six groups according to perfusion mode and oxygenator type. Laboratory parameters, fluid balance and oxygenation was examined at set times before during and after cardiopulmonary bypass. Net fluid input was lower in the Capiox E groups regardless of perfusion mode: 2932 +/- 562 ml (Capiox E), compared to 3646 +/- 531 ml (Ultrox) and 3593 +/- 582 ml (Maxima). Net fluid balance 1288 +/- 534 ml was lowest in the Capiox/NP group, compared to 1604 +/- 460 ml (Ultrox/NP) and 1881 +/- 594 ml (Maxima/NP), (p < 0.05). The higher net fluid balance in the Capiox E/PP group 1649 +/- 580 ml compared to 1592 +/- 583 ml (Ultrox E/PP) and 1494 +/- 542 ml (Maxima/PP) was attributed to a technicality whereby the recommended priming volume of the Capiox E oxygenator was exceeded for safety reasons. The values of plasma free Hb were slightly higher in the PP than NP groups: Maxima/PP 80 mg/dl, /NP 50 mg/dl; Ultrox/PP 62 mg/dl, /NP 48 mg/dl; Capiox E/PP 55 mg/dl, /NP 48 mg/dl. The FiO2 was higher in the Capiox E groups 0.77 (PP) and 0.88 (NP) compared to Maxima/PP (0.66), /NP (0.65) and Ultrox/PP (0.64), /NP (0.63). Reciprocally, the venous saturation was higher in the Ultrox and Maxima groups compared to Capiox E at end of CPB. The study demonstrated that the CapioxE oxygenator with a single blood pump system can compare to the Maxima and Ultrox oxygenators with a double blood pump for CPB with regard to blood handling, oxygenation and fluid balance in routine cardiac surgery.

Blood Gas Analysis↗
PubMed1996

Cloning and sequencing of human gp330, a Ca(2+)-binding receptor with potential intracellular signaling properties.

We present here the complete primary structure of human gp330, the human variant of the principal kidney autoantigen causing Heymann membranous glomerulonephritis in rats. The deduced 4655 amino acid residues give a calculated molecular mass of 519636 Da for the mature protein and consists of a probable 25-amino-acid N-terminal signal peptide sequence, an extracellular region of 4398 amino acids, a single transmembrane-spanning domain of 23 amino acids, and an intracellular C-terminal region of 209 amino acid residues. Three types of cysteine-rich repeats characteristic of the low density lipoprotein receptor (LDLR) superfamily are present in human gp330. In the extracellular region, there are a total of 36 LDLR ligand-binding repeats, comprising four distinct domains, 16 growth factor repeats separated by eight YWTD spacer regions, and one epidermal growth factor-like repeat. No consensus cleavage sequence for the processing endoprotease furin is detected in human gp330. The intracellular tail contains not only two copies of the F(X)NPXY coated-pit mediated internalization signal characteristic of LDLR superfamily members, but also intriguing and potentially functional motifs including several Src-homology 3 recognition motifs, one Src-homology 2 recognition motif for the p85 regulatory subunit of phosphatidylinositol 3-kinase, and additional sites for protein kinase C, casein kinase II and cAMP-/cGMP-dependent protein kinase. There is approximately 77% amino acid identity between human and rat gp330 with minor differences between the extracellular and intracellular regions. Recently gp330 has been implicated in Ca2+ regulation in the parathyroid, the placenta, and the renal tubule, but its overall physiological and pathological role still remains uncertain.

Amino Acid Sequence↗
PubMed1996

Low insertion of hepatic segmental duct VII-VIII is an important cause of major biliary injury or misdiagnosis.

BACKGROUND: The importance of variant anatomy is only mentioned generally in most articles in this era of laparoscopic cholecystectomy. We report a series of 14 patients in whom a seemingly low insertion of hepatic segmental duct VII-VIII was clinically important. METHODS: The patients were managed at Duke University Medical Center. Two intraoperative videotapes of injury were reviewed. RESULTS: Three categories of patients were identified: 6 patients who had injury in association with another major injury to the biliary system, 7 patients who had an isolated VII-VIII system injury, and 1 patient with a Klatskin tumor in whom the unobstructed variant duct was stented. After appropriate evaluation, all patients were successfully treated. Several lawsuits resulted, even when the injury was seemingly minor. Symptoms developed in all patients who filed lawsuits, but none in those who did not. CONCLUSION: Appreciation of the VII-VIII biliary variant can lead to avoidance of injury or to a successful repair. The injury can easily occur despite "normal" cholangiography. Successful clinical outcome does not necessarily correlate with freedom from lawsuits.

Bile Duct Neoplasms↗
PubMed1996

Disposition of a novel recombinant antithrombotic agent, RG 12986, in cynomolgus monkeys.

RG 12986, a novel antagonist of platelet aggregation, is a recombinant peptide based on the sequence in von Willebrand factor, which contains the GP1b binding site. Disposition of the peptide in cynomolgus monkeys was determined using nonlabeled and 35S-labeled product. After iv administration, the peptide underwent a triphasic decay in the plasma. The first phase of elimination, after distribution, had a t1/2 (approximately 20 min) similar to that observed for inhibition of platelet aggregation (approximately 25 min). The correlation between the logarithm of the plasma peptide concentration and activity was r = 0.9989. The effective duration of pharmacological activity was approximately 2 hr. After this period, a slower terminal phase of plasma elimination was observed (t1/2 approximately 2 hr). Plasma clearance (7-15 ml/min/kg) and volume of distribution at steady-state (0.4-0.9 L/kg) estimates appeared to have a slight dose dependency, but the scope of the investigation did not allow this to be verified. There was a linear correlation between dose and AUC (r2 = 0.9998), but for each 4-fold increase in dose there was a greater than 4-fold increase in AUC. Immediately after iv administration, significant fragmentation of the peptide was observed with polyacrylamide gel electrophoresis analysis of the plasma. This initial rate of metabolism was subsequently slowed to t1/2 estimates of 2 hr, followed by a very long terminal half-life of plasma radioactivity of 12 days. It is likely that this terminal half-life represents metabolic recycling of 35S. Elimination of the label was primarily via the kidneys.

Animals↗