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Biomedical subjects

R Edwards

Publications and source records attributed to R Edwards.

At least 145 records · Page 8Linked to original sources
PubMed1997

Leptin levels do not change acutely with food administration in normal or obese subjects, but are negatively correlated with pituitary-adrenal activity.

BACKGROUND: Leptin is a peptide secreted by white adipose tissue which has been shown to have a major influence on body weight regulation, while animal studies have revealed widespread interconnections between leptin and other endocrine systems, especially with insulin. However, its acute regulation has been little studied in the human. We have therefore investigated the effect of a 1000 kcal meal and fasting on the levels of leptin, insulin and cortisol, in both normal and obese subjects. SUBJECTS AND DESIGN: We have studied the effect of food and fasting on circulating leptin levels in 20 subjects of normal body mass index (BMI range 18-25) and in a group of 12 moderately-severely obese subjects (BMI range 34-61). We also studied the effect of food and fasting in a patient both before and after the successful removal of a pancreatic insulinoma as a model of excess insulin secretion. RESULTS: Mean leptin levels were significantly higher in the obese than in the lean group (42.7 +/- 3.41 vs 5.35 +/- 1.55 micrograms/l, mean +/- SEM; P < 0.001), and showed a positive correlation with body mass index (r = +0.71; P < 0.001). Frequent (every 20 minutes) sampling for 3 hours after food did not show any acute changes in circulating leptin levels. On the fasting day we observed a small but significant fall in circulating leptin levels in the last 4 hours of a 20-hour fast in our subjects as a group (92 +/- 0.03% of basal, P = 0.03); however, in the lean subjects the fall was greater (86 +/- 0.04% of basal, P = 0.02) than in the obese, where it did not reach statistical significance (96 +/- 0.05% of basal). Pre-meal and peak insulin levels showed a positive correlation with circulating mean leptin levels (r = +0.65; P < 0.001 and r = +0.78; P < 0.001, respectively) in all subjects, while pre-meal and peak serum cortisol levels showed an inverse relation with leptin levels (r = -0.53; P = 0.002 and r = -0.41; P = 0.02, respectively); this effect was independent of BMI in the obese subjects. In the patient with the insulinoma the markedly elevated insulin and leptin levels measured before the operation returned to normal after removal of the tumour, in accord with reports of experimental animal data that long-term insulin excess per se is associated with increased circulating leptin concentrations. CONCLUSION: Leptin is a robust indicator of BMI and insulin levels, both basal and stimulated, but does not change acutely following food. Fasting causes a proportionately greater decline in leptin levels in lean subjects than in obese subjects. Circulating leptin is inversely correlated with the activity of the hypothalamo-pituitary-adrenal axis: whether this is a direct influence of leptin on hypothalamo-pituitary-adrenal activity, or whether both are indirect indicators of body fat stores, requires further investigation.

Adult↗
PubMed1997

Functional and genetic studies of the angiotensin II type 1 receptor in pre-eclamptic and normotensive pregnant women.

OBJECTIVE: To examine and compare angiotensin II type 1 receptor genotype and its relationship to platelet angiotensin II binding for pre-eclamptic and normotensive pregnant women. DESIGN: In a case-control study, 43 pre-eclamptic women and 83 normotensive women were genotyped at the angiotensin II type 1 receptor gene locus. Platelet angiotensin II binding was measured for a subset of 11 pre-eclamptic and 57 normotensive pregnant women. We genotyped 162 healthy blood donors also, to examine the allelic background and patterns of linkage disequilibrium in the Nottingham population. METHODS: Patients were recruited during pregnancy using a rigorous definition of pre-eclampsia. DNA was extracted from peripheral venous blood and genotyped at six previously described diallelic polymorphisms in the angiotensin II type 1 receptor gene, using competitive allele-specific oligonucleotide hybridization, and at a dinucleotide repeat polymorphism in the 3' flanking region of the gene. Platelet angiotensin II binding and plasma angiotensin II concentrations were determined for peripheral venous blood. RESULTS: Normotensive pregnant women homozygous for cytosine at nucleotide 573 had significantly higher levels of platelet angiotensin II binding than did heterozygous women and women homozygous for thymidine at this site. Pre-eclamptic women had significantly higher levels of platelet angiotensin II binding than did normotensive pregnant women. The frequencies of allelic variants did not differ significantly between normotensive and pre-eclamptic women. CONCLUSION: The physiological regulation of platelet angiotensin II type 1 receptor expression in normal pregnancy is determined in part by angiotensin II type 1 receptor genotype. There was no evidence that the polymorphisms in the angiotensin II type 1 receptor gene were associated with pre-eclampsia.

Adult↗
PubMed1997

Resistance to beta-lactam antibiotics in Bacteroides spp.

Bacteroides spp., particularly B. fragilis, are well-recognised bacterial pathogens. Production of the typical beta-lactamases of Bacteroides restricts the therapeutic use of beta-lactam agents mainly to the beta-lactamase inhibitor combinations and carbapenems. These compounds have the advantage of broad-spectrum activity and the ability to combat polymicrobial infections. Resistance of Bacteroides spp. to beta-lactam antibiotics appears to be increasing, largely because of an overall increase in beta-lactamase activity. There has been a rise in the prevalence of isolates showing high-level production of typical Bacteroides beta-lactamases and an increase in reports other potent beta-lactamase types. In the case of B. fragilis, metallo-enzymes are a particular threat to current therapeutic practice, as they are not inhibited by common beta-lactamase inhibitors and are able to hydrolyse carbapenems. The presence of permeability barriers may confer low-level beta-lactam resistance and supplement the effect of beta-lactamase activity. There are also sporadic reports of loss of beta-lactam activity because of reduced affinity of the penicillin-binding proteins.

Anti-Bacterial Agents↗
PubMed1997

Genetic differentiation of Australian isolates of Mycobacterium tuberculosis by pulsed-field gel electrophoresis.

As part of an epidemiological study of tuberculosis in Australia, 84 isolates of Mycobacterium tuberculosis from patients were analysed by pulsed-field gel electrophoresis (PFGE). The isolates were genetically heterogeneous, with 66 different DNA banding patterns obtained following digestion of genomic DNA with Dra1 and 53 patterns with Xba1. When the results were compared with those previously obtained in restriction fragment length polymorphism analysis (RFLP), in 87% of cases the results with Dra1 were consistent with those obtained with insertion sequence IS6110 as a probe in RFLP. However, PFGE was able to differentiate four of eight isolates which were identical with IS6110 typing. The high polymorphism amongst strains and the high average age of the patients (51 years) suggested that most organisms were cultured from patients who had reactivation of existing infections. Isolates with identical DNA patterns were found in different states of Australia, but no one strain predominated in any area. This suggests that tuberculosis has been introduced into Australia from various sources.

Adolescent↗
PubMed1997

The effect of zinc ions on the activity of metallo-beta-lactamases of Bacteroides fragilis.

The zinc supplement required to achieve the maximum activity of metallo-beta-lactamases from 12 Bacteroides fragilis isolates was investigated. Changes in absorbance of imipenem in a spectrophotometric assay with crude cell extracts were performed in the presence and absence of various concentrations of zinc sulphate. The greatest degree of imipenem hydrolysis was seen with the addition of between 50 and 500 microM zinc sulphate, and the degree of stimulation of enzyme activity in the strains tested varied six-fold. Increasing the zinc sulphate concentration resulted in inhibition of hydrolysis with extracts of low enzymic activity. These findings indicate the importance of determining the optimal zinc concentration for each strain tested in kinetic studies of metallo-beta-lactamases.

Bacteroides fragilis↗
PubMed1997

Development of a PCR assay for rapid diagnosis of Mycobacterium ulcerans infection.

The diagnosis of Mycobacterium ulcerans infection is hampered by the slow growth of the bacterium in culture, resulting in a delay of several months before a specific diagnosis can be obtained. In addition, M. ulcerans cannot be isolated from water even when there is convincing epidemiological evidence implicating this as the source of infection. The aim of the present study was to develop a PCR assay to circumvent the problems of delayed diagnosis and insensitivity of standard bacterial culture for M. ulcerans. For the PCR, we isolated an M. ulcerans-specific DNA fragment, 1,109 bp long, which is repeated at least 50 times throughout the genome. Use of this sequence as a target for PCR allowed us to detect as few as 2 molecules of genomic DNA in vitro. The PCR was used to detect M. ulcerans DNA in fresh tissue and paraffin-embedded sections from all seven patients with culture-confirmed cases of infection.

Base Sequence↗
PubMed1997

Development of enzyme immunoassay for endogenous ouabain-like compound in human plasma.

Widespread evidence supports the existence of an endogenous digitalis-like compound in mammals. We report here the development of a novel enzyme immunoassay for ouabain that, in conjunction with a detailed HPLC study, identifies a ouabain-like compound (OLC) in extracted human plasma. The assay is sensitive-minimum detection limit for OLC 37 pmol/L (11 pmol/L in plasma)-and has a working range (between-assay CV < 10%) of 180-10000 pmol/L (54-3000 pmol/L in plasma). Mean recoveries of ouabain added to plasma ranged from 90% to 100%, and plasma extracts diluted in parallel to the standard curve. Plasma OLC concentrations in 10 healthy volunteers averaged 92 pmol/L (range 55-168), assuming 100% cross-reactivity of OLC in the ouabain assay. HPLC analysis with two distinct chromatographic conditions demonstrated that endogenous human plasma OLC co-eluted with authentic ouabain. The enzyme immunoassay is rapid and easy to perform and will support further investigation of the nature of this controversial endogenous steroid.

Chromatography, High Pressure Liquid↗
PubMed1996

Expression of cytokine genes or proteins and signaling molecules in lymphocytes associated with human ovarian carcinoma.

We have reported that tumor-associated T or natural killer (NK) lymphocytes purified from ascites of women with ovarian carcinoma show defective expression and function of signaling proteins, including reduced expression of TcR-zeta chains and p56(lck). In this study, the cytokine profiles of both tumor cells and tumor-associated lymphocytes (TAL) recovered from the tumor milieu were examined. Expression of cytokine genes was studied by semi-quantitative RT-PCR and Southern hybridization, and the presence of intracellular cytokine proteins was confirmed by immunostaining. Levels of mRNA encoding the cytokine genes typically transcribed in activated T lymphocytes, including IFN-gamma, IL-2 and IL-4, were markedly reduced, as was expression of the corresponding proteins, in TAL-T or TAL-NK cells relative to normal PBL-T or PBL-NK cells, respectively. Levels of TGF-beta and IL-6 were unaltered, while those of IL-10 were up-regulated. Although both tumor cells and TALs contributed to the enhanced level of IL-10 expression, a higher proportion of TAL-T lymphocytes than normal PBL-T cells expressed IL-10 protein. The altered profile of cytokine genes and proteins in TALs, TAL-T or TAL-NK cells was associated with impaired expression and/or function of signaling molecules, zeta chain and p56(lck). Our data suggest that abnormalities in signal transduction commonly seen in lymphocytes obtained from the tumor micro-environment are related to the concomitantly observed altered patterns of expression of cytokine transcripts and proteins.

Adult↗
PubMed1996

Effect of smoking cessation on cervical lesion size.

BACKGROUND: Cigarette smoking has been postulated as a cofactor in the aetiology of cervical cancer, but a causal role is difficult to establish because of potential confounding by sexual behaviour. We have investigated the effect of cessation or reduction of cigarette smoking on the course of minor-grade cervical lesions. METHODS: In this intervention study 82 women volunteers with minor-grade lesions on colposcopy (cervical intraepithelial neoplasia grade 1 or less) attempted to give up smoking for 6 months. Smoking histories were taken at 3-monthly clinic visits and verified by measurement of salivary cotinine concentrations. At each clinic visit, a photograph of the cervix was taken; the image was digitised and computer-aided image analysis was used to assess lesion size, by investigators unaware of smoking status. FINDINGS: Of the 82 women, 17 stopped smoking completely for at least 6 months and 11 others reduced their smoking consumption by more than 75%. Of these 28 women, 23 (82%) showed a reduction in lesion size of at least 20% or 4 mm2 compared with 13 (28%) of the 47 non-quitters (odds ratio 12.0 [95% Cl 3.9-32.7]). The remaining seven women had unconfirmed smoking histories. There was a significant correlation between the extent of smoking reduction and the change in lesion size (chi2 for trend=31.55, p<0.0001). Adjustment for social class, method of contraception, and stage of menstrual cycle did not affect the results. INTERPRETATION: Our findings support a link between smoking and cervical disease and suggest that smoking cessation could have a beneficial effect on early cervical abnormalities.

Adult↗
PubMed1996

Nursing management and follow-up of the postoperative vascular patient in a clinic setting.

Patient follow-up after vascular surgery in a clinic setting provides prompt evaluation of patients, opportunity for education, and comprehensive care through direct patient and family teaching. These services are provided by a lead clinic RN experienced in medical/surgical care and a certified RN first assistant, who has specialized training and proficiency in perioperative nursing practice. Patients and their families depend on nurses in perioperative and outpatient settings to provide expertise, support, and understanding during the recovery process. This article presents a collaborative model of intervention, management, and follow-up by nurses in these settings.

Aftercare↗
PubMed1996

Ensenanzas en un gimnasio: an investigation of modeling and verbal rehearsal on the motor performance of Hispanic limited English proficient children.

This study investigated the effects of modeling and verbal rehearsal on the motor performance of English-speaking and limited English proficient (LEP) children. Children (N = 64) in 4th-grade classes were randomly assigned to conditions in a 2 x 2 x 2 x 2 (Gender x Primary Language x Model Type x Rehearsal) factorial design. Boys and girls whose primary language was English or Spanish were assigned to either a verbal model or no-model condition as well as to a verbal rehearsal or no-rehearsal condition of the motor skills required to be performed. Analysis of variance revealed a significant Model Type x Primary Language interaction as well as a significant Rehearsal x Primary Language interaction. Follow-up analyses revealed that English-speaking children provided with a verbal rehearsal strategy recalled significantly more skills than English-speaking children in the no-rehearsal condition; for LEP children, there were no differences due to rehearsal. Moreover, LEP children presented with a verbal model recalled significantly more skills than LEP children in the no-model condition; for English-speaking children, there were no differences attributed to model type. These results indicate that effective modeling conditions that are provided with verbal cues in English are related to children's primary language.

Child↗
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↗