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Biomedical subjects

R Edwards

Publications and source records attributed to R Edwards.

At least 163 records · Page 9Linked to original sources
PubMed1996

Mechanisms responsible for reduced susceptibility to imipenem in Bacteroides fragilis.

The mechanisms responsible for reduced susceptibility to imipenem (MIC 2-16 mg/L) were investigated in eight strains of Bacteroides fragilis. All the strains produced elevated levels of beta-lactamase. Four B. fragilis strains produced metallo-beta-lactamase capable of marked imipenem hydrolysis, and these enzymes were shown to be responsible for resistance. There was evidence, from testing susceptibility to imipenem in the presence of clavulanic acid, that increased resistance in two strains was associated with susceptibility to beta-lactamases other than metallo-enzymes. With the remaining two strains there was no evidence of enzymic breakdown of imipenem. Neither of these strains showed evidence of decreased permeability to nitrocefin as judged by a method which takes into account the substrate concentration in the periplasmic space. A low molecular weight PBP, that was not seen in fully sensitive strains of B. fragilis, was detected in four strains in which reduced susceptibility to imipenem was not associated with metallo-beta-lactamase activity.

Anti-Bacterial Agents↗
PubMed1996

Nosocomial outbreak of tuberculosis in an outpatient HIV treatment room.

OBJECTIVE: To investigate a possible outbreak of tuberculosis in an outpatient HIV treatment facility in Sydney, Australia. DESIGN: Following the diagnosis of pulmonary tuberculosis in an attendee, a prospective screening program was instituted to investigate the potential outbreak. METHODS: Screening of 89 potentially exposed patients included chest radiographs (n = 89), and sputum examination (n = 37) over a period of 23 weeks. RESULTS: No cases of tuberculosis were detected by the screening program. However, three (3.4%) of this cohort developed pulmonary tuberculosis between 8 and 10 weeks following diagnosis of the index case. The incidence of active tuberculosis during the following-up period (median, 7.4 months) was 5.3 per 100 person years and represents the lower limit of possible tuberculous infection, as both latent infection, and undiagnosed tuberculosis among those who died could not be excluded. Mycobacterium tuberculosis strains isolated from the index case and three subsequent cases were found to be identical by DNA typing. CONCLUSION: Nosocomial transmission of tuberculosis in an outpatient treatment setting has been demonstrated. The risk of nosocomial transmission of tuberculosis is significant in institutions caring for HIV-infected patients even in countries with a low prevalence of tuberculosis infection, and highlights the importance of adherence to tuberculosis control guidelines.

AIDS-Related Opportunistic Infections↗
PubMed1996

An enzyme immunoassay for 6-sulphatoxy-melatonin in human urine.

We describe a newly developed enzyme immunoassay (EIA) for the determination of 6-sulphatoxy-melatonin (aMT6s) in human urine, using a aMT6s-bovine serum albumin-horseradish peroxidase (aMt6s-BSA-HRP) conjugate as the enzyme label. The assay incorporates a highly specific antibody raised in rabbits. The EIA has a sensitivity of 2 pg/well (40 pg/ml) with intraassay coefficients of variation of 2.3-6.1% in the range of the assay. The material with the highest level of cross-reactivity was N-acetyl serotonin sulphate, with a relative potency of 0.000078%. One hundred thirty-four urine samples from children and adults at different time points were assayed and the results compared with those from an established radioimmunoassay (RIA) and with a newly developed RIA using the same antibody as the EIA. The correlation coefficient, r, comparing the two RIA's was 0.9869, and the regression equation was log (kit) = 0.9340 log (new) + 0.1213. The correlation coefficient, r, comparing the EIA with the newly developed RIA, was 0.9686, and regression equation log (new) = 0.9674 log (EIA) + 0.0600. The EIA for the measurement of aMT6s in urine represents a new approach in the investigation of pineal function.

Adolescent↗
PubMed1996

Acromegaly presenting with diabetic ketoacidosis.

Diabetes in acromegaly is usually non-insulin dependent and is secondary to insulin resistance caused by growth hormone excess. Diabetic ketoacidosis is a result of relative insulin deficiency and is a rare feature of acromegaly. We describe a case of acromegaly presenting with diabetic ketoacidosis. We demonstrate that growth hormone excess can cause diabetic ketoacidosis in the presence of relative, but not absolute insulin deficiency.

Acromegaly↗
PubMed1996

Short-term night-shift working mimics the pituitary-adrenocortical dysfunction in chronic fatigue syndrome.

The purpose of this study was to determine whether a short period (5 days) of night-shift work affected the pituitary-adrenal responses to CRH. Ten nurses (8 female and 2 male; age 28.1 +/- 1.7 yr: mean +/- SEM) working at the Royal Liverpool University Hospital, and who regularly undertook periods of night and day shift work were enrolled. Measurements were made of basal ACTH and cortisol concentrations, and their responses to iv ovine CRH (1 microgram.kg-1). Basal ACTH concentrations were higher during the night shift than during the day shift (12.9 +/- 5.1 pmol.L-1 vs. 4.7 +/- 1.2 pmol.L-1, P < 0.01) whereas cortisol concentrations were lower (551 +/- 48 nmol.L - 1 vs. 871 +/- 132 nmol.L - 1, P < 0.01). After CRH injection, ACTH concentrations remained consistently higher during the night shift, but the integrated increase in ACTH concentration was lower (P < 0.05) than during the day shift. Conversely, the increase in cortisol concentration was greater during the night shift than the day shift (283 +/- 53 nmol.L-1 vs. 134 +/- 41 nmol.L-1, P < 0.05). We conclude that the pituitary-adrenal responses to CRH are markedly disrupted after only 5 days of nighttime work. These abnormalities mimic those previously observed in patients with chronic fatigue syndrome. Neuroendocrine abnormalities reported to be characteristic of chronic fatigue syndrome may be merely the consequence of disrupted sleep and social routine.

Adrenal Cortex↗
PubMed1996

Concepts in risk-benefit assessment. A simple merit analysis of a medicine?

The term 'benefit-risk ratio' is often used as a general term linked to the use of a medicine. To balance risk and benefit is, however, a very complex exercise. For most medicines the benefits are limited to a few indications and for an individual patient there is usually only a single benefit sought but the potential risks are multiple. Perceptions of risks versus benefits are influenced to a great extent by the context in which they occur. Thus, perception of risk may be different to actual risk. In the end in any given situation, the acceptable risk-to-benefit balance is an individual judgement on the part of the patient or the prescriber. For newer medicines, where there is likely to be limited experience, conservative estimates of the overall merit seem preferable so that the prescriber will use the drug critically. Subsequently, re-evaluation of the risk-to-benefit balance is necessary as greater knowledge of efficacy and adverse effects is acquired. It is possible to provide a general 'principle of threes' structure for a merit assessment based upon the concepts of seriousness, duration and incidence as related to disease indication, disease amelioration by a medicine, and the adverse effects ascribed to the medicine. This allows a rapid first comparison of medicines for a given indication. In using this general conceptual model in a transparent fashion for a given hypothesis and context, it is possible to identify the essential data used and assumptions involved that make up a merit statement. The quality and value, particularly of risk data, is problematic. Risk perception is an issue that needs to be clearly identified alongside a merit analysis. A simple merit assessment should pave the way for more focused studies.

Drug Therapy↗
PubMed1995

Simultaneous resistance to metronidazole, co-amoxiclav, and imipenem in clinical isolate of Bacteroides fragilis.

A blood-culture isolate of Bacteroides fragilis, taken from a woman after elective laparotomy, was resistant to metronidazole and had reduced susceptibility to imipenem and co-amoxiclav. After treatment with imipenem, pus drained from the pleural cavity yielded an identical isolate that had become highly resistant to imipenem and co-amoxiclav. Emergence of full resistance to the beta-lactam antibiotics was accompanied by a tenfold rise in the specific activity of a metallo-beta-lactamase. Clinicians need to be alert to simultaneous resistance to metronidazole, co-amoxiclav, and imipenem and development of high-level resistance to imipenem in B fragilis during treatment with this agent.

Adult↗
PubMed1995

The role of uridylyltransferase in the control of Klebsiella pneumoniae nif gene regulation.

The glnD gene in enteric bacteria encodes a uridylyltransferase/uridylyl-removing enzyme which acts as the primary nitrogen sensor in the nitrogen regulation (Ntr) system. We have investigated the role of this enzyme in transcriptional regulation of nitrogen fixation genes in Klebsiella pneumoniae by cloning glnD from this organism and constructing a null mutant by insertional inactivation of the chromosomal gene using the omega interposon. K. pneumoniae glnD encodes a 102.3 kDa polypeptide which is highly homologous to the predicted products of both Escherichia coli glnD and Azotobacter vinelandii nfrX. The glnD-omega mutant was unable to uridylylate PII and was altered in adenylylation/deadenylylation of glutamine synthetase. Uridylyltransferase was required for derepression of ntr-regulated promoters such as glnAp2 and pnifL but was not involved in the nif-specific response to changes in nitrogen status mediated by the nifL product. We conclude that a separate, as yet uncharacterised, nitrogen control system may be responsible for nitrogen sensing by NifL.

Amino Acid Sequence↗
PubMed1995

Changes in protein methylation associated with the elicitation response in cell cultures of alfalfa (Medicago sativa L.).

The methylation of endogenous proteins increased in alfalfa cell suspension cultures following treatment with a fungal elicitor. Carboxyl methylation, a post-translational modification associated with controlling the localisation and longevity of proteins, was the dominant form of protein methylation in both elicited and unelicited cells. Protein methylation was restricted to a limited number of peptides prior to elicitor treatment but as elicitation progressed the number of endogenous substrates increased. Increases resulted from a combination of an elicitor-dependent increase in the activity of a protein carboxyl methyltransferase and the accumulation of preferred endogenous substrates in the latter stages of elicitation.

Cells, Cultured↗
PubMed1995

Epidemiology and practice of emergency medicine in a developing country.

STUDY OBJECTIVE: To analyze the emergency medicine system in a developing country and identify areas of need and potential collaboration. DESIGN: Convenience sample surveys of all emergency visits over a 2-week period, hospital admission and health department statistics, and interviews with government officials, health providers, and EMS managers. SETTING: Port of Spain General Hospital, Trinidad and Tobago. RESULTS: The ED has more than 100,000 visits per year. No records are kept. No physician in this study had emergency medicine training; only one had completed any residency. The survey included 3,710 patients: 40.5% were admitted, and .3% died. Injuries accounted for 41.6% of all visits, asthma 7.8%. The mean time elapsed before a patient was seen was .5 hour; mean time to discharge, 1.9 hours. In only 9% of patients were laboratory tests performed. Prehospital providers had limited equipment and training. CONCLUSION: The ED and prehospital systems provide high-volume and often high-acuteness care. Barriers to improved care include limited specialized training and lack of medical records.

Adolescent↗
PubMed1995

A comparison of the efficacy and tolerability of moclobemide given as a single daily dose or in three divided doses per day for the treatment of patients with a major depressive episode (DSM-III-R)

This was a prospective, double-blind, randomized, multicenter trial comparing moclobemide once daily (OD) with three times daily (TDS) dosing. The duration of the study was 6 weeks with the initial dose of moclobemide being 450 mg/day (either 450 mg in the morning or 150 mg three times daily). Placebo tablets were used to ensure that the study was double blind. After 2 weeks, the dose could be increased to 600 mg/day if tolerability was acceptable and efficacy was judged insufficient by the investigator. Patients were assessed at baseline and at days 3, 7, 14, 21, 28, and 42. Efficacy was primarily judged on the Hamilton Rating Scale for Depression (HAM-D) (17item). Patients had to score at least 17 to enter the study. Safety and tolerability were judged on reported adverse events, safety parameters, premature withdrawals, and a physicians' global tolerability rating. There were also three secondary efficacy parameters--the Hamilton Rating Scale for Anxiety, Visual Analogue Scales for pain and irritability, and physicians' Clinical Global Impression (CGI). A total of 130 evaluable patients were required to detect a difference of more than 20% (alpha = 0.05 and beta = 0.8) between groups. A total of 189 patients entered the study, and the standard analysis comprised 145 patients. The efficacies between the two dosing regimens as determined by the HAM-D score and from the CGI were found not to differ significantly. For the standard analysis population, there was a reduction in mean HAM-D of 73.8 and 72.9% for the OD and TDS groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Benzodiazepines attenuate the pituitary-adrenal responses to corticotrophin-releasing hormone in healthy volunteers, but not in patients with Cushing's syndrome.

OBJECTIVE: The corticotrophin-releasing hormone (CRH) stimulation test has become established as a powerful tool in differentiating the source of ACTH in patients with Cushing's syndrome. Psychiatric symptoms are common in patients with Cushing's syndrome, and many patients with psychiatric illnesses may show disturbances of function of the pituitary-adrenal axis; both of these groups of patients may be receiving benzodiazepine drugs when presenting for evaluation of their possible endocrine problems. Both animal and human studies suggest that interactions occur between benzodiazepines and the hypothalamo-pituitary-adrenal axis. We have therefore evaluated the effects of a benzodiazepine drug on the pituitary-adrenal response to CRH. DESIGN: We have investigated the effects of 20 mg oral temazepam or placebo on serum cortisol and plasma ACTH after the administration of 100 micrograms i.v. human CRH in 12 healthy volunteers and in 9 patients with Cushing's syndrome. RESULTS: Temazepam significantly inhibited the peak serum/plasma levels and area under the curve for circulating cortisol and ACTH in normal subjects after CRH, but there was no such difference after temazepam in patients with Cushing's syndrome. CONCLUSIONS: Our results have shown that temazepam inhibits the pituitary-adrenal responses to human CRH in normal subjects, but not in those with Cushing's syndrome. We believe that inhibition of endogenous AVP by temazepam is the most likely explanation for our findings in healthy volunteers: the hypercortisolaemia in Cushing's syndrome suppresses the release of both endogenous CRH and AVP in portal blood which then results in abolition of the temazepam induced reduction in the pituitary-adrenal response to exogenous CRH, as seen in our patients. These effects of benzodiazepines should clearly be taken into account in patients using these compounds while undergoing endocrine assessment.

Adrenocorticotropic Hormone↗