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Biomedical subjects

J Donovan

Publications and source records attributed to J Donovan.

At least 19 recordsLinked to original sources
PubMed2006

Hypothalamic mapping of orexigenic action and Fos-like immunoreactivity following relaxin-3 administration in male Wistar rats.

The insulin superfamily, characterized by common disulphide bonds, includes not only insulin but also insulin-like peptides such as relaxin-1 and relaxin-3. The actions of relaxin-3 are largely unknown, but recent work suggests a role in regulation of food intake. Relaxin-3 mRNA is highly expressed in the nucleus incertus, which has extensive projections to the hypothalamus, and relaxin immunoreactivity is present in several hypothalamic nuclei. In the rat, relaxin-3 binds and activates both relaxin family peptide receptor 1, which also binds relaxin-1, and a previously orphaned G protein-coupled receptor, RXFP3. These receptors are extensively expressed in the hypothalamus. The aims of these studies were twofold: 1) map the hypothalamic site(s) of the orexigenic action of relaxin-3 and 2) examine the site(s) of neuronal activation following central relaxin-3 administration. After microinjection into hypothalamic sites, human relaxin-3 (H3; 180 pmol) significantly stimulated 0- to 1-h food intake in the supraoptic nucleus (SON), arcuate nucleus (ARC), and the anterior preoptic area (APOA) [SON 0.4+/-0.2 (vehicle) vs. 2.9+/-0.5 g (H3), P<0.001; ARC 0.7+/-0.3 (vehicle) vs. 2.7+/-0.2 g (H3), P<0.05; and APOA 0.8+/-0.1 (vehicle) vs. 2.2+/-0.2 g (H3), P<0.05]. Cumulative food intake was significantly increased<or=8 h following administration into the SON and 4 h into the APOA. A significant increase in Fos-like immunoreactivity was seen in the SON following central relaxin-3 administration. Relaxin-3 stimulates feeding in several hypothalamic nuclei, and these studies provide additional support for relaxin-3 as an important peptide in appetite regulation.

Animals↗
PubMed2006

Relationship of vascular risk to the progression of Alzheimer disease.

OBJECTIVE: To test the hypothesis that patients with Alzheimer disease (AD) who have vascular risk factors have a worse prognosis over 18 months vs those without such risk factors. METHODS: A sample of 224 people with AD and their caregivers were recruited purposively to be representative of people with dementia in terms of cognition, sex, and living situations in a longitudinal study of AD. Standardized instruments measuring cognition, functional status, and neuropsychiatric symptoms were used to collect data. Physical examination and relevant blood tests were performed. RESULT: There was no difference in rate of deterioration between people with and without vascular risk factors, except in those who had a cerebrovascular accident (CVA) during the 18-month follow-up (p < 0.001). We considered possible confounders of outcome: sex, age, years of education, severity of dementia, depression, taking cholinesterase inhibitors (AChEIs), and whether those with vascular risk factors were more likely to die, but the results remained unchanged. Stopping AChEIs during the study was associated with cognitive and functional decline (p < 0.001). CONCLUSIONS: Vascular risk factors as measured clinically and biochemically do not significantly increase deterioration at 18 months in people with Alzheimer disease who have a low burden of cerebrovascular risk factors. However, cerebrovascular events are associated with more rapid decline. Vascular risk factors may contribute to the expression of Alzheimer disease initially but are not part of the underlying etiologic process.

Aged↗
PubMed2006

Effects of acute and chronic relaxin-3 on food intake and energy expenditure in rats.

The effects of acute and repeated intraparaventricular (iPVN) administration of human relaxin-3 (H3) were examined on food intake, energy expenditure, and the hypothalamo-pituitary thyroid axis in male Wistar rats. An acute high dose iPVN injection of H3 significantly increased food intake 1 h post-administration [0.4+/-0.1 g (vehicle) vs 1.6+/-0.5 g (180 pmol H3), 2.4+/-0.5 g (540 pmol H3) and 2.2+/-0.5 g (1,620 pmol H3), p<0.05 for all doses vs vehicle]. Repeated iPVN H3 injection (180 pmol/twice a day for 7 days) significantly increased cumulative food intake in ad libitum fed animals compared with vehicle [211.8+/-7.1 g (vehicle) vs 261.6+/-6.7 g (ad libitum fed H3), p<0.05]. Plasma leptin was increased in the H3 ad libitum fed group. Plasma thyroid stimulating hormone was significantly decreased after acute and repeated administration of H3. These data suggest H3 may play a role in long-term control of food intake.

Acute Disease↗
PubMed2006

Eosinophilic cystitis: successful long-term treatment with montelukast sodium.

We report a rare case of eosinophilic cystitis in a 6-year-old boy who presented with irritative voiding symptoms, peripheral eosinophilia, and a bladder mass initially visualized on ultrasonography. Cystoscopy and transurethral biopsy confirmed the diagnosis. Complete resolution of his symptoms occurred within 1 week of corticosteroid use and the x-ray findings improved within 6 weeks. At 6 months of follow-up, the patient continued to require a leukotriene receptor antagonist (montelukast sodium) despite several attempts to discontinue its use. We propose that eosinophilic cystitis in children who present with peripheral eosinophilia will often require long-term treatment.

Acetates↗
PubMed2006

Coronary calcification, homocysteine, C-reactive protein and the metabolic syndrome in Type 2 diabetes: the Prospective Evaluation of Diabetic Ischaemic Heart Disease by Coronary Tomography (PREDICT) Study.

AIMS: The PREDICT Study aims to determine: (i) the association between cardiovascular risk factors and coronary artery calcification score (CACS) obtained by electron beam tomography and (ii) the predictive value of CACS for coronary heart disease (CHD) events in Type 2 diabetes. METHODS: Having previously reported relationships between CACS and conventional risk factors, we have now studied the novel risk factors, plasma high-sensitivity C-reactive protein (CRP) and homocysteine, insulin resistance, serum apoprotein A1 and B concentrations, the serum triglyceride/high-density lipoprotein cholesterol ratio and metabolic syndrome (International Diabetes Federation definition) in 573 subjects of the PREDICT Type 2 diabetes cohort. RESULTS: In univariate analyses, the only significant positive novel correlate of CACS was homocysteine (P = 0.0004). CRP was increased in those with detectable calcification, but decreased with increasing calcification score (P = 0.006). In a multivariate model that included all significant univariate correlates, CACS was independently associated with age (P < 0.0001), waist-hip ratio (P < 0.02), male gender (P < 0.05) and duration of diabetes (P < 0.05), but the association with homocysteine was no longer significant. The negative association between CACS and CRP remained in multivariate analysis, and was independent of statin use. CONCLUSIONS: Age was the major factor influencing CACS in Type 2 diabetes, with weaker contributions from waist hip-ratio and duration of diabetes. Other novel cardiovascular risk factors appear to have little positive effect.

Adult↗
PubMed2006

Risk factors for graft survival after liver transplantation from donation after cardiac death donors: an analysis of OPTN/UNOS data.

Due to increasing use of allografts from donation after cardiac death (DCD) donors, we evaluated DCD liver transplants and impact of recipient and donor factors on graft survival. Liver transplants from DCD donors reported to UNOS were analyzed against donation after brain death (DBD) donor liver transplants performed between 1996 and 2003. We defined a recipient cumulative relative risk (RCRR) using significant risk factors identified from a Cox regression analysis: age; medical condition at transplantation; regraft status; dialysis received and serum creatinine. Graft survival from DCD donors (71% at 1 year and 60% at 3 years) were significantly inferior to DBD donors (80% at 1 year and 72% at 3 years, p < 0.001). Low-risk recipients (RCRR < or = 1.5) with low-risk DCD livers (DWIT < 30 min and CIT < 10 h, n = 226) achieved graft survival rates (81% and 67% at 1 and 3 years, respectively) not significantly different from recipients with DBD allografts (80% and 72% at 1 and 3 years, respectively, log-rank p = 0.23). Liver allografts from DCD donors may be used to increase the cadaveric donor pool, with favorable graft survival rates achieved when low-risk grafts are transplanted in a low-risk setting. Whether transplantation of these organs in low-risk recipients provides a survival benefit compared to the waiting list is unknown.

Cadaver↗
PubMed2005

Association between quality of life scores and short-term outcome after surgery for cancer of the oesophagus or gastric cardia.

BACKGROUND: Evidence suggests that baseline quality of life (QOL) scores are independently prognostic for survival in patients with cancer, but the role of QOL data in predicting short-term outcome after surgery is uncertain. This study assessed the association between QOL scores and short-term outcomes after surgery for oesophageal and gastric cancer. METHODS: Consecutive patients selected for oesophagectomy or total gastrectomy between November 2000 and May 2003 completed the European Organization for Research and Treatment of Cancer's quality of life questionnaire, QLQ-C30. Multivariable regression models, adjusting for known clinical risk factors, were used to investigate relationships between QOL scores, major morbidity, hospital stay and survival status at 6 months. RESULTS: Of 130 patients, 121 completed the questionnaire (response rate 93.1 per cent). There were 29 major complications (24.0 per cent) and 22 patients (18.2 per cent) died within 6 months of operation. QOL scores were not associated with major morbidity but were significantly related to survival status at 6 months after adjusting for known clinical risk factors. A worse fatigue score of 10 points (scale 0-100) corresponded to an increase in the odds of death within 6 months of surgery of 37.4 (95 per cent confidence interval (c.i.) 12.4 to 67.8) per cent (P = 0.002). Pretreatment social function scores were moderately associated with hospital stay (P = 0.021); a reduction in social function by 10 points corresponded to an increase in hospital stay of 0.93 (95 per cent c.i. 0.12 to 1.74) days. CONCLUSION: QOL scores supplement standard staging procedures for oesophageal and gastric cancer by providing prognostic information, but they do not contribute to perioperative risk assessment.

Adult↗
PubMed2003

Long-term effectiveness of operative procedures for Stanford type A aortic dissections.

BACKGROUND: To evaluate long-term effectiveness of strategies for managing the aortic root and distal aorta in type A dissections. METHODS: From 1990 to 1999, 50 patients (32 men, 64.07%; 18 women, 36.0%; mean age 57.4 y +/- 11.1) underwent operation for ascending aortic dissection. Surgical strategies included aortic root replacement with a composite graft (21/50; 42.0%), valve replacement with supracoronary ascending aortic graft (3/50, 6%), and valve preservation or repair (26/50; 52.0%). RESULTS: Overall hospital mortality rate was 18.0%. Follow-up was completed for 47 patients (94.0%) and ranged from 1 month to 10.5 years (mean 28.8 months). Actuarial survival for patients discharged from the hospital was 84% at 1 year, 75% at 5 years, and 66% at 10 years. There was no significant difference between the various procedures regarding mortality, neurological complications, long term survival and proximal re-operations. The ascending aorta alone was replaced in 8/50 patients (16%), ascending and hemiarch in 30/50 patients (60%) and arch and proximal descending aorta in 12/50 patients (24%) Hospital mortality (11.5, 20.0 and 16.7% respectively; p > 0.05) and 5- and 10-year survival (p > 0.05) were not statistically dependent on the extension of the resection distally. Residual distal dissection was not associated with a decrease in late survival. With regard to emergency surgery (36/50) there was no significant difference in hospital mortality (p > 0.05) and 5 year survival (p > 0.05) between those who had undergone coronary angiography (19/36; 52.8%) on the day of surgery with those who had not (17/36; 47.2%). CONCLUSIONS: Preservation or repair of the aortic valve can be recommended in the majority of patients with type A dissection. Distal extension of the resection does not increase surgical risk. Residual distal dissection does not decrease late survival. Preoperative coronary angiography may not affect survival in patients undergoing emergency surgery.

Adult↗
PubMed2003

Population requirement for primary knee replacement surgery: a cross-sectional study.

OBJECTIVES: To determine the population requirement for total knee replacement (TKR) in England. METHODS: Population-based study using an age/sex-stratified random sample of 28 080 individuals aged 35 yr and over. Incident disease was estimated from prevalence by statistical modelling. The New Zealand priority criteria for major joint replacement were used for case selection. RESULTS: Patients with knee disease were less likely than those with equally severe hip disease to have been referred to a specialist, to have consulted an orthopaedic surgeon or to be on a waiting list for joint replacement. The estimated annual requirement of TKRs in England, based on New Zealand Scores alone, was 55,800 (95% CI 40 700-70,900), contrasting sharply with an annual provision of 29,300 actually observed. However, in contrast to previously reported hip replacement data, when patient willingness to undergo surgery was considered, this estimate decreased considerably. CONCLUSIONS: There appears to be an underprovision of TKR in England. This may be due in part to differences in perception of disease severity and likely response to surgery between patients and general practitioners on one hand, and rheumatologists and orthopaedic surgeons on the other.

Adult↗
PubMed2002

Outcomes following quadriceps tendon ruptures.

Complete rupture of the quadriceps femoris tendon is a well-described injury. There is a scarcity of literature relating to the outcome of patients with this injury after surgery. We undertook a retrospective analysis of patients who had surgical repair of their ruptured quadriceps tendon at our institution over a seven year period-totalling 27 patients. Males were more commonly affected with a M:F ratio of 8:1. The peak incidence was in the sixth decade of life. The non-dominant limb was twice as likely to be affected. Assessment consisted of completion of a functional knee questionnaire, clinical examination and isokinetic testing on a Biodex dynanometer. Symptomatic outcome following surgical repair was excellent with a mean symptom score generated of 22.7 out of a maximum of 25. 18/19 patients returned to their premorbid level of activity on average 18.1 weeks following injury. There was no difference in quadriceps girth comparing affected and unaffected limbs. Less than 5 degrees deficit in range of motion existed between affected and unaffected limbs. Approximately two-thirds of patients were the same or better when comparing peak torque/body weight, average power, maximum average peak torque and total work/body weight in affected and unaffected limbs.

Adult↗
PubMed2002

Rates of cholesterol esterification and esterified cholesterol net mass transfer between high-density lipoproteins and apolipoprotein B-containing lipoproteins in Type 1 diabetes.

AIMS: Type 1 diabetes is associated with a high incidence of coronary heart disease (CHD) despite paradoxically normal or high high-density lipoprotein (HDL) cholesterol concentrations. Triglyceride (TG) concentrations have been shown to be important determinants of two aspects of HDL metabolism: cholesterol esterification rate and esterified cholesterol (EC) net mass transfer rate between HDL and the apolipoprotein B-containing lipoproteins. In order to try to explain the paradox, we aimed to assess the relationships between plasma TG and these two processes in Type 1 diabetic compared with non-diabetic subjects. METHODS: Rates of cholesterol esterification and EC net mass transfer between HDL and the apolipoprotein B-containing lipoproteins were assessed by incubating whole plasma at 37 degrees C; intra-assay coefficients of variation were 6% and 30%, respectively. RESULTS: Ten Type 1 diabetic and 10 non-diabetic subjects, with similar ages, sex distributions, body mass indices and total cholesterol and TG concentrations, were assessed. Apolipoprotein A1, HDL unesterified cholesterol, and HDL phospholipid concentrations were greater in the Type 1 diabetic subjects. There were no significant differences in the rates of cholesterol esterification or EC net mass transfer between the groups. There were strong associations between plasma TG and the rate of cholesterol esterification and between plasma TG and the rate of EC net mass transfer in Type 1 diabetic subjects (r = 0.83, P = 0.0027 and r = 0.88, P = 0.0009, respectively) and in non-diabetic subjects (r = 0.91, P = 0.0002 and r = 0.79, P = 0.0070, respectively). However, the slopes of the associations with plasma TG were significantly steeper in the Type 1 diabetic subjects (analyses of covariance P = 0.0053 and P = 0.0146, respectively). CONCLUSIONS: Increases in TG may therefore promote more EC enrichment of atherogenic apolipoprotein B-containing lipoproteins in Type 1 diabetes while also promoting more cholesterol esterification, thereby maintaining HDL cholesterol concentrations. This could contribute to the paradox of high CHD incidence despite normal or high HDL cholesterol concentrations in Type 1 diabetes.

Adult↗
PubMed2002

Relationship between the birth cohort pattern of Helicobacter pylori infection and the epidemiology of duodenal ulcer.

BACKGROUND: Helicobacter-pylori-related duodenal ulcer (DU) is an important cause of dyspepsia. AIM: To determine the relationship between the pattern of H. pylori infection and the epidemiology of duodenal ulcer in a single population. DESIGN: Prospective two-part study of (i) patients with DU referred for endoscopy because of dyspepsia, and (ii) the incidence of H. pylori infection in the general population of the same area. METHODS: Details of 533 DU patients were recorded, and related to the pattern of H. pylori infection among 10 537 adults in the same community, determined by the (13)C-urea breath test. RESULTS: In patients with DU, birth year was more important than age in determining the rate of presentation for endoscopy (the 'birth cohort' effect). H. pylori infection showed a similar birth cohort effect, and the prevalence decreased steadily in those born in successive years, from 28.8% in the 1930s to 3.5% in the 1970s. The proportion of dyspeptic patients who had duodenal ulcers also fell progressively, from 22.2% in 1979 to 5.7% in 1998. H. pylori prevalence and duodenal ulcer incidence were closely correlated at all ages. DISCUSSION: Duodenal ulcer prevalence (as judged by the rate of referral of duodenal ulcer patients for endoscopy) is determined principally by the distribution of H. pylori infection in the local population. The birth cohort effect seen in adult duodenal ulcer patients reflects the acquisition of H. pylori in childhood. In Bristol, H. pylori prevalence and duodenal ulcer incidence are both declining to very low levels.

Adult↗
PubMed2001

Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1.

Blood glucose levels are maintained by the balance between glucose uptake by peripheral tissues and glucose secretion by the liver. Gluconeogenesis is strongly stimulated during fasting and is aberrantly activated in diabetes mellitus. Here we show that the transcriptional coactivator PGC-1 is strongly induced in liver in fasting mice and in three mouse models of insulin action deficiency: streptozotocin-induced diabetes, ob/ob genotype and liver insulin-receptor knockout. PGC-1 is induced synergistically in primary liver cultures by cyclic AMP and glucocorticoids. Adenoviral-mediated expression of PGC-1 in hepatocytes in culture or in vivo strongly activates an entire programme of key gluconeogenic enzymes, including phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, leading to increased glucose output. Full transcriptional activation of the PEPCK promoter requires coactivation of the glucocorticoid receptor and the liver-enriched transcription factor HNF-4alpha (hepatic nuclear factor-4alpha) by PGC-1. These results implicate PGC-1 as a key modulator of hepatic gluconeogenesis and as a central target of the insulin-cAMP axis in liver.

3T3 Cells↗