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Biomedical subjects

G Williams

Publications and source records attributed to G Williams.

At least 163 records · Page 9Linked to original sources
PubMed1999

The effect of moxonidine on feeding and body fat in obese Zucker rats: role of hypothalamic NPY neurones.

The antihypertensive agent moxonidine, an imidazoline Ii-receptor agonist, also induces hypophagia and lowers body weight in the obese spontaneously hypertensive rat, but the central mediation of this action and the neuronal pathways that moxonidine may interact with are not known. We studied whether moxonidine has anti-obesity effects in the genetically-obese and insulin-resistant fa/fa Zucker rat, and whether these are mediated through inhibition of the hypothalamic neuropeptide Y (NPY) neurones. Lean and obese Zucker rats were given moxonidine (3 mg kg(-1) day(-1)) or saline by gavage for 21 days. Moxonidine decreased food intake throughout by 20% in obese rats (P<0.001) and by 8% in lean rats (P<0.001), and reduced weight gain that final body weight was 15% lower in obese (P<0.001) and 7% lower in lean (P<0.01) rats than their untreated controls. Plasma insulin and leptin levels were decreased in moxonidine-treated obese rats (P<0.01 and P<0.05), but unchanged in treated lean rats. Uncoupling protein-1 gene expression in brown adipose tissue was stimulated by 40-50% (P< or =0.05) in both obese and lean animals given moxonidine. Obese animals given moxonidine showed a 37% reduction in hypothalamic NPY mRNA levels (P = 0.01), together with significantly increased NPY concentrations in the paraventricular nucleus (P<0.05), but no changes in the arcuate nucleus or other nuclei; this is consistent with reduced NPY synthesis in the arcuate nucleus and blocked release of NPY in the paraventricular nucleus. In lean animals, moxonidine did not affect NPY levels or NPY mRNA. The hypophagic, thermogenic and anti-obesity effects of moxonidine in obese Zucker rats may be partly due to inhibition of the NPY neurones, whose inappropriate overactivity may underlie obesity in this model.

Adipose Tissue↗
PubMed1999

Effect of synthetic triglycerides of myristic, palmitic, and stearic acid on serum lipoprotein metabolism.

OBJECTIVES: To determine relative effects of diets high in synthetic sources of myristic (14:0), palmitic (16:0) or stearic (18:0) acid on concentrations and metabolism of serum lipoproteins. DESIGN: Eighteen healthy women participated in a three-way cross-over study for five week periods separated by seven week washout periods, diets were assigned in random order. SUBJECTS: Premenopausal women, not on medication, were from three races (Caucasian, African-American, Asian) and four apolipoprotein E phenotype groups (3/3, 3/2, 4/3, and 4/2). INTERVENTION: During the first week the subjects consumed a baseline diet providing 11 energy (en)% saturated fat, 10en% polyunsaturated fat and 14en% monounsaturated fat. Followed by test diets with 19en% saturated fat (including 14en% test saturated fatty acid), 3en% polyunsaturated fat, and 14en% monounsaturated fat for four weeks. Synthetic fats (trimyristin, tripalmitin, and tristearin) were used in blends with natural fats and oils. RESULTS: Mean concentrations of serum total, esterified and LDL cholesterol were significantly lower after 18:0 than after 16:0 (n = 16-18, P < 0.01 for treatment effect). Myristic acid (14:0) had an intermediate effect. Receptor-mediated degradation of 125I-LDL in mononuclear cells obtained from the subjects was lower after 16:0 than after 14:0 and 18:0 (n = 16-18, P=0.05 for treatment effect). Differences in the digestibilities of the fats were not a major factor in the results. Strong cholesterolemic responses to the 16:0 diet were partly explained by apoE phenotype. CONCLUSIONS: As noted previously, stearic acid was neutral compared to 14:0 and 16:0. In contrast to studies involving natural fats, 14:0, fed as a synthetic triglyceride, was less cholesterolemic than 16:0 in a majority of subjects. ApoE phenotype influenced the cholesterolemic response particularly when diets high in 16:0 were eaten.

Adult↗
PubMed1999

Obesity and type 2 diabetes: a conflict of interests?

Obesity is a major risk factor for the development of type 2 diabetes and is an important obstacle to the management of this disease. The increasing incidence of both obesity and type 2 diabetes makes management of these related conditions particularly important. Conventional approaches to the management of type 2 diabetes that focus primarily on improving glycaemic control-notably insulin or sulphonylurea treatment-often lead to weight gain, which is particularly detrimental to patients with type 2 diabetes. By contrast, reducing body weight in such patients improves glycaemic control and other cardiovascular risk factors associated with the metabolic syndrome. This suggests that weight reduction is a rational option in the management of obese patients with type 2 diabetes. While reductions in body weight of approximately 10% have been achieved in some studies, this is difficult to achieve in real life, especially for patients with type 2 diabetes. Weight management agents such as sibutramine and orlistat, used as part of an integrated programme of diet, physical activity and behavioural therapy, are thus an attractive early option for the management of type 2 diabetes in obese patients.

Anti-Obesity Agents↗
PubMed1999

Altered sodium perception in essential hypertensive patients following rapid volume expansion.

We investigated sodium and volume-dependent mechanisms in the modulation of adrenal and renal vascular responsiveness to angiotensin II in hypertensive (n = 9) and normal subjects (n = 5) who demonstrated normal responses during steady-state salt balance (intact modulation). Adrenal and renal vascular responses to angiotensin II were assessed on four occasions. These studies were performed during steady-state high salt and low salt balance and later during non-steady state conditions, after acute volume expansion with normal saline or dextran infusions. The volume expansion studies were administered while study subjects were in low salt balance. In both the normal and hypertensive patients saline and dextran suppressed plasma renin activity and aldosterone release, induced renal vasodilation and enhanced the renal vascular response to angiotensin II, similar to that observed during high salt balance. Saline also reduced the adrenal response to angiotensin II in normal subjects but the adrenal response to angiotensin II in hypertensives remained enhanced. The slopes of regression lines relating angiotensin II and aldosterone following saline infusion were significantly different (P < 0.05) between normal subjects (21 +/- 6) and hypertensives (110 +/- 33). Volume expansion with dextran did not effect the normal or hypertensive adrenal response to angiotensin II. We have demonstrated that the renal vascular response to angiotensin II is rapidly modulated by volume expansion per se in normal subjects and hypertensive patients with intact steady-state renin-angiotensin-aldosterone system responses. However, hypertensives have a delay in resetting the adrenal responsiveness to angiotensin II suggesting that they have altered sodium perception during rapid changes in salt balance.

Adrenal Cortex↗
PubMed1999

Divergent effects of intracerebroventricular and peripheral leptin administration on feeding and hypothalamic neuropeptide Y in lean and obese (fa/fa) Zucker rats.

Leptin inhibits feeding and decreases body weight. It may act partly by inhibiting hypothalamic neurons that express neuropeptide Y, a powerful inducer of feeding and obesity. These neuropeptide Y neurons express the Ob-Rb leptin receptor and are overactive in the fatty (fa/fa) Zucker rat. The fa mutation affects the extracellular domain of the leptin receptor, but its impact on leptin action and neuropeptide Y neuronal activity is not fully known. We compared the effects of three doses of leptin given intracerebroventricularly and three doses of leptin injected intraperitoneally on food intake and hypothalamic neuropeptide Y mRNA, in lean and fatty Zucker rats. In lean rats, 4-h food intake was reduced in a dose-related fashion (P<0.01) by all intracerebroventricular leptin doses and by intraperitoneal doses of 300 and 600 microg/kg. Neuropeptide Y mRNA levels were reduced by 28% and 21% after the highest intracerebroventricular and intraperitoneal doses respectively (P<0. 01 for both). In fatty rats, only the highest intracerebroventricular leptin dose reduced food intake (by 22%; P<0. 01). Neuropeptide Y mRNA levels were 100% higher in fatty rats than in lean animals, and were reduced by 18% (P<0.01) after the highest intracerebroventricular leptin dose. Intraperitoneal injection had no effect on food intake and neuropeptide Y mRNA. The fa/fa Zucker rat is therefore less sensitive to leptin given intracerebroventricularly and particularly intraperitoneally, suggesting that the fa mutation interferes both with leptin's direct effects on neurons and its transport into the central nervous system. Obesity in the fa/fa Zucker rat may be partly due to the inability of leptin to inhibit hypothalamic neuropeptide Y neurons.

Animals↗
PubMed1999

Association between - 308 tumour necrosis factor promoter polymorphism and bronchial hyperreactivity in asthma.

BACKGROUND: Tumour necrosis factor (TNF) is a pivotal cytokine in the inflammation underlying asthma. The TNF gene is located in the polymorphic HLA class 3 region on chromosome 6p. Several polymorphisms in this region have been described and associated with alteration of TNF secretion in vitro. OBJECTIVE: In this study we tested the hypothesis that two such polymorphisms, lymphotoxin alpha NcoI B*1 and -308 TNF2 may be components of the genetic predisposition to asthma. METHODS: Five hundred and fifty-six random individuals were studied, comprising approximately equal numbers of asthmatic subjects, with or without atopy, and a nonatopic nonasthmatic control group. In addition, 355 subjects (172 asthmatics) from 60 multiplex families were typed at the LTalpha NcoI locus. RESULTS: There was an association between allele two of the -308 TNF polymorphism and bronchial hyperreactivity (OR 2.12, 95% CI 1.04-4.32, P = 0.036). However, there was no association with LTalpha NcoI alleles. To determine whether this was influenced by linkage disequilibrium within the MHC, 91 subjects with bronchial hyperreactivity and 85 control subjects were typed for class 2 and 3 alleles. Following identification of the extended TNF2 haplotype, we found no independent association of these alleles with BHR. CONCLUSIONS: We conclude that the -308 TNF2 promoter polymorphism may form a component of the genetic predisposition to BHR in asthma.

Adolescent↗
PubMed1999

Transurethral resection or incision of the prostate and other therapies: a survey of treatments for benign prostatic obstruction in the UK.

OBJECTIVE: To establish the current usage of transurethral incision of the prostate (TUIP) and other forms of treatment for benign prostatic obstruction (BPO). METHODS: The Prostate Trial Office (PROTO) sent a survey questionnaire to all 376 consultant urologists in the UK which asked for estimates of their clinical practice in treating BPO. The survey had three principle aims: to assess the role that the determination of prostate size has in clinical practice, to determine the nature and frequency of use of a range of therapies including TUIP, and to examine the feasibility of conducting a randomized controlled trial comparing transurethral resection of the prostate (TURP) and TUIP. RESULTS: Of the 376 urologists, 349 replied (response rate 93%); most respondents used prostate size as a determinant when deciding on therapy for BPO (60%). Of their patients with BPO who were treated, 38% received surgical treatment, 33% drug therapies and 29% conservative management. Of the types of surgical treatment, the most commonly used procedure was TURP, in 79% of patients, with only 15% undergoing TUIP. When compared with TURP, TUIP tended to be used for patients with a mean prostate volume of </=25 mL. Only 6% of surgical patients were treated using minimally invasive techniques. CONCLUSION: This survey provides some evidence that prostate size plays an important role in determining the treatment; TUIP appeared to be under-used and other minimally invasive techniques are rarely used in the UK.

Adult↗
PubMed1999

Regulation of neuropeptide Y release by neuropeptide Y receptor ligands and calcium channel antagonists in hypothalamic slices.

Neuropeptide Y (NPY) is an important regulator of energy balance in mammals through its orexigenic, antithermogenic, and insulin secretagogue actions. We investigated the regulation of endogenous NPY release from rat hypothalamic slices by NPY receptor ligands and calcium channel antagonists. High-potassium stimulation (60 mM) of the slices produced a calcium-dependent threefold increase in NPY release above basal release. The Y2 receptor agonists NPY(13-36) and N-acetyl[Leu28,Leu31]NPY(24-36), the Y4 agonist rat pancreatic polypeptide (rPP), and the Y4/Y5 agonist human pancreatic polypeptide (hPP) significantly reduced both basal and stimulated NPY release. NPY(13-36)-induced reduction of NPY release could be partially prevented in the presence of the weak Y2 antagonist T4-[NPY(33-36)]4, whereas the hPP- and rPP-induced inhibition of release was not affected by the Y5 antagonist CGP71683A or the Y1 antagonist BIBP3226. The selective Y1, Y2, and Y5 antagonists had no effect on either basal or potassium-stimulated release when administered alone. The calcium channel inhibitors omega-conotoxin GVIA (N-type), omega-agatoxin TK (P/Q-type), and omega-conotoxin MVIIC (Q-type) all significantly inhibited potassium-stimulated NPY release, without any effect on basal release, whereas nifedipine had no effect on either basal or stimulated release. Addition of both omega-conotoxin GVIA and omega-agatoxin TK together completely inhibited the potassium-stimulated release. In conclusion, we have demonstrated that NPY release from hypothalamic slices is calcium-dependent, involving N-, P-, and Q-type calcium channels. NPY release is also inhibited by Y2 agonists and rPP/hPP, suggesting that Y2 and Y4 receptors may act as autoreceptors on NPY-containing nerve terminals.

Agatoxins↗
PubMed1999

Decreased plasma leptin levels in lean and obese Zucker rats after treatment with the serotonin reuptake inhibitor fluoxetine.

Leptin inhibits feeding, stimulates thermogenesis and decreases body weight. Serotonin reduces food intake when injected into the hypothalamus and may interact with other neurotransmitters in the control of appetite. We therefore investigated the effects of the serotonergic drug fluoxetine, which inhibits serotonin reuptake, on food intake and plasma leptin levels in lean and obese Zucker rats. Fluoxetine significantly reduced food intake in lean and obese rats, both acutely after a single injection (10 mg/kg) and during continuous subcutaneous infusion (10 mg/kg/day for 7 days). Plasma leptin levels were reduced after both 4 hours and 7 days of fluoxetine administration in lean and after 7 days in fatty rats (all p<0.01). We have previously suggested that serotonin may decrease food intake by inhibiting neuropeptide Y neurones, and we further suggest that it also inhibits leptin, possibly by an effect on white adipose tissue.

Animals↗
PubMed1999

Intravesical administration of radiolabelled tumour-associated monoclonal antibody in bladder cancer.

Considerable progress has been made over the past decade in the use of tumour-associated monoclonal antibodies (mAbs) as carriers of cytotoxic agents in the management of several malignancies. In the present study we investigated the tumour localization and biodistribution of the mAb HMFG1 to bladder cancer following intravesical administration. HMFG1, which has been raised against the polymorphic epithelial mucin (PEM), was labelled with 125I and administered intravesically 2 h and 24 h before cystoscopy. During cystoscopy, biopsies were taken from the normal bladder and the malignant lesion. Tissue samples were tested for HMFG1 immunostaining and for radioactivity with the use of a gamma-counter. The mean ratio of tumour to normal uptake for 125I-HMFG1 was 5.81 +/- 1.23, at 2 h and 2.17 +/- 0.42 at 24 h. No radioactivity was detected in the blood. We conclude that HMFG1 could be used intravesically for the successful delivery of a cytotoxic agent.

Administration, Intravesical↗
PubMed1999

Towards evidence-based health promotion and service provision for new migrants to Australia.

OBJECTIVES: To examine patterns of health utilization and health information dissemination among immigrants to Australia in the first 6 months of immigration using data from the Longitudinal Study of Immigrants to Australia (LSIA). METHODS: The population for the LSIA consists of 5178 principal applicants making their first arrival to Australia on a migrant visa between 1 September 1993 and 31 August 1995, inclusive, and who are aged 15 years or over at the time (96% of all principal applicants). The influence of immigration category, country of birth, health status and age on the likelihood of receiving information about health, sources of health information and use of general practitioners were explored using separate logistic regressions for men and women. RESULTS: Women who received health information were older and less likely to have a chronic illness than women who did not. Men who received health information were older and more likely to be in the Business visa category. Younger women, those in Preferential Family visa categories and bilingual women were more likely than other women to have received health information from an NGO. For men, the only significant predictor of source of health information was being in the Independent visa category. Women who used health services were younger, more likely to have a chronic illness, be proficient in English and less likely to be in the Independent visa category than women who did not. Men who used health services were older, more likely to have a chronic condition and have limited English than men who did not. Men who used health services were more likely to be in the Humanitarian visa class and less likely to be in the Concessional Family or Business visa categories than men who did not use health services. They were also more likely to have been born in Oceania, Middle East and North Africa and Africa. CONCLUSIONS: The results of this study indicate that there are important differentials in knowledge of and use of the health system and these differences are unlikely to be captured by using measures based on ethnicity or country of origin alone. Predictors of health service utilization were different for men and women. In particular, age and lack of English proficiency appeared to be barriers to health service use for women. Visa category and country of birth were more important determinants of health service use for men.

Adult↗
PubMed1999

Delayed complications following Tenckhoff catheter removal.

BACKGROUND: Tenckhoff catheter placement is well established to facilitate continuous ambulatory peritoneal dialysis (CAPD) in the treatment of end-stage renal failure. Complications of these catheters while in situ are well documented. However, little information is available concerning post-removal complications. Many centres, including our own remove these catheters by traction resulting in retained cuffs, rather than by formal dissection. We have evaluated the outcome of such removal over a 2-year period. METHODS: Sixty-two patients underwent Tenckhoff catheter removal by traction over a 2-year period at our unit. Patients were evaluated retrospectively using case notes and operation records. RESULTS: The catheters were sited for a mean of 23 months and were most commonly removed because of persistent peritonitis (48.4%). Sixty-one per cent of all patients had experienced at least one episode of CAPD peritonitis while the catheter was in situ, but this did not correlate with those who developed local sepsis. Fifteen patients (24.2%) subsequently developed local infective complications after a mean of 5.7 months (range 1-17 months). The subcutaneous cuff was involved in all cases and the peritoneal cuff was involved in six cases. Thirty patients were identified as being immunosuppressed, but this was not a risk factor in the development of retained cuff infections. CONCLUSIONS: There is a significant risk of local sepsis with retained cuffs resulting from removal by traction and our data suggests that these catheters should be removed by dissection and excision of both cuffs.

Adult↗
PubMed1999

Generation and analysis of 25 Mb of genomic DNA from the pufferfish Fugu rubripes by sequence scanning.

We have generated and analyzed >50,000 shotgun clones from 1059 Fugu cosmid clones. All sequences have been minimally edited and searched against protein and DNA databases. These data are all displayed on a searchable, publicly available web site at. With an average of 50 reads per cosmid, this is virtually nonredundant sequence skimming, covering 30%-50% of each clone. This essentially random data set covers nearly 25 Mb (>6%) of the Fugu genome and forms the basis of a series of whole genome analyses which address questions regarding gene density and distribution in the Fugu genome and the similarity between Fugu and mammalian genes. The Fugu genome, with eight times less DNA but a similar gene repertoire, is ideally suited to this type of study because most cosmids contain more than one identifiable gene. General features of the genome are also discussed. We have made some estimation of the syntenic relationship between mammals and Fugu and looked at the efficacy of ORF prediction from short, unedited Fugu genomic sequences. Comparative DNA sequence analyses are an essential tool in the functional interpretation of complex vertebrate genomes. This project highlights the utility of using the Fugu genome in this kind of study.

Animals↗
PubMed1999

Crisis management to controlled recovery: the emergency planning response to the bombing of Manchester City Centre.

Fuelled by terrorist attacks on urban areas, emergency planning responses to manmade disasters is a growing area of critical debate within the field of urban management. The response of a major British city--Manchester--to the 1996 bombing of its commercial core, is examined in this paper. It focuses on the transformation of the emergency planning response from dealing with the immediate crisis during the first week, to a stage of controlled recovery that still continues. The response to the devastation caused by the bomb was co-ordinated by the city council, which developed a range of short- and long-term initiatives, but the re-opening of the city centre could not have happened so quickly had the council not worked in collaboration with other key organisations and agencies. Working partnerships were crucial to the immediate response and subsequent recovery, with such capacity for organisational learning built upon existing co-operative arrangements within the city, which had developed over the previous decade.

Crisis Intervention↗
PubMed1999

Molecular subtyping of Clostridium perfringens by pulsed-field gel electrophoresis to facilitate food-borne-disease outbreak investigations.

Clostridium perfringens is a common cause of food-borne illness. The illness is characterized by profuse diarrhea and acute abdominal pain. Since the illness is usually self-limiting, many cases are undiagnosed and/or not reported. Investigations are often pursued after an outbreak involving large numbers of people in institutions, at restaurants, or at catered meals. Serotyping has been used in the past to assist epidemiologic investigations of C. perfringens outbreaks. However, serotyping reagents are not widely available, and many isolates are often untypeable with existing reagents. We developed a pulsed-field gel electrophoresis (PFGE) method for molecular subtyping of C. perfringens isolates to aid in epidemiologic investigations of food-borne outbreaks. Six restriction endonucleases (SmaI, ApaI, FspI, MluI, KspI, and XbaI) were evaluated with a select panel of C. perfringens strains. SmaI was chosen for further studies because it produced 11 to 13 well-distributed bands of 40 to approximately 1,100 kb which provided good discrimination between isolates. Seventeen distinct patterns were obtained with 62 isolates from seven outbreak investigations or control strains. In general, multiple isolates from a single individual had indistinguishable PFGE patterns. Epidemiologically unrelated isolates (outbreak or control strains) had unique patterns; isolates from different individuals within an outbreak had similar, if not identical, patterns. PFGE identifies clonal relationships of isolates which will assist epidemiologic investigations of food-borne-disease outbreaks caused by C. perfringens.

Centers for Disease Control and Prevention, U.S.↗