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J O'Dowd

Publications and source records attributed to J O'Dowd.

17 recordsLinked to original sources
PubMed2006

Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 reduces food intake and weight gain but maintains energy expenditure in diet-induced obese mice.

AIMS/HYPOTHESIS: The 11beta-hydroxysteroid dehydrogenase type-1 inhibitor BVT.2733 lowers blood glucose and insulin in mutant mouse models of obesity and diabetes. Its effects on energy balance and body composition, and their contribution to improved glucose homeostasis have received little attention. MATERIALS AND METHODS: BVT.2733 (100 mg/kg, orally) was given twice daily to lean and diet-induced obese mice for 16 or 17 days. A group of obese mice was pair-fed to the amounts consumed by BVT.2733-treated mice. RESULTS: In both obese and lean mice, BVT.2733 reduced food intake and weight gain, but increased water intake. Pair-feeding caused almost as great a decrease in body weight as BVT.2733. Energy expenditure was 38+/-8% higher in the BVT.2733-treated obese mice than in the pair-fed mice. Terminal plasma corticosterone was raised, lean body weight reduced and percentage fat unchanged in the pair-fed mice (control, 47.8+/-2.6%; pair-fed, 47.1+/-1.9%), whereas BVT.2733 did not reduce lean mass, but did reduce percentage fat (40.9+/-2.0%). BVT.2733 but not pair-feeding reduced both the glucose tolerance AUC and the plasma insulin concentration 30 min after giving glucose. CONCLUSIONS/INTERPRETATION: BVT.2733 reduced food intake but prevented a concomitant reduction in lean body mass and energy expenditure. The latter effects may have contributed to improved glucose tolerance.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2005

Analysis of an adult Duchenne muscular dystrophy population.

BACKGROUND: Advances in management have led to increasing numbers of patients with Duchenne muscular dystrophy (DMD) reaching adulthood. Older patients with DMD are necessarily severely disabled, and their management presents particular practical issues. AIM: To review the management of a late adolescent and adult DMD population, and to identify areas in which the present service provisions may be inadequate to their needs. DESIGN: Retrospective review. METHODS: We studied 25 patients with DMD referred to an adult neuromuscular clinic over a 7-year period. Clinical details were obtained retrospectively, from case notes or direct observations. RESULTS: There were 24 males and one symptomatic female carrier. Nine patients died during the observation period. There was no significant correlation between age of wheelchair confinement and age of death. Sixteen patients received non-invasive positive pressure support. Twelve attended mainstream schools and 12, residential special schools. All the patients lived at home for some or all of the time, when their main carers were either one or both of the parents. The most striking difficulties were with the provision of practical aids, including appropriate hoists and belts, feeding and toileting aids, and the conversion of accommodation. Patients rarely wished to discuss the later stages of their disease, and death was often more precipitate than expected. Death usually occurred outside hospital and the final cause was often difficult to establish. DISCUSSION: Adult patients with DMD develop progressive impairment, due to respiratory, orthopaedic and general medical factors. However, the particular areas of difficulty in this study often reflected inadequate and poorly directed social and medical support, illustrating the need for improvements in the structure, co-ordination and breadth of rehabilitation services for adult patients with DMD.

Adolescent↗
PubMed2004

Modulation of susceptibility to weight gain and insulin resistance in low birthweight rats by treatment of their mothers with leptin during pregnancy and lactation.

OBJECTIVES: To investigate whether administration of leptin to rats during pregnancy and lactation affects placental 11beta-hydroxysteroid dehydrogenase (11beta-HSD2) activity and the susceptibility of their offspring to weight gain and insulin resistance. DESIGN: Pregnant rats fed on a low-protein diet were administered leptin or saline by subcutaneous minipump from day 14 of gestation and throughout lactation. A further group was fed a normal diet and given saline. After weaning, the offspring of each group were fed on a normal diet until 6 weeks of age and then half of each group was transferred to a high-fat diet until 12 months of age. RESULTS: Plasma leptin levels were raised two-fold on days 16-18 of pregnancy in the leptin-treated dams, but, despite a constant rate of infusion, at parturition they dipped to control levels before rising again. The activity of placental 11beta-HSD2 was reduced by the low-protein diet; this reduction was prevented by treating the dams with leptin. The male offspring of the saline-treated dams gained more weight and had higher plasma leptin levels on the high fat than the chow diet, but the offspring of the leptin-treated dams did not. Fasting blood glucose and intraperitoneal glucose tolerance at 6 and 12 months of age was unaffected by the high-fat diet, but only the offspring of the leptin-treated dams achieved this control without raised insulin levels. CONCLUSIONS: The rate of leptin clearance appears to increase at parturition. The administration of leptin to rats during late pregnancy and lactation makes their male offspring less susceptible to high-fat-diet-induced weight gain and insulin resistance.

Animals↗
PubMed2003

Borderline nuclear change in cervical smears: five-year follow-up.

Borderline nuclear changes (BNC) account for 5-20% of cervical smears, and their outcome is unpredictable. Current management involves repeat smears at 6-mo intervals, for a further 12 mo with referral for colposcopy, if the changes persist. Given the uncertainty surrounding the natural history of BNC and the claim that many patients are further investigated unnecessarily and potentially "overtreated," the aim of this study was to determine the outcome for patients with a diagnosis of BNC to define whether the management protocol is appropriate for this patient group in our laboratory. A total of 808 patients with BNC were followed up. There was a 4.05% progression to high-grade dyskaryosis, and most of these were detected within the first year of follow-up. This at least justifies the early and intense follow-up of this patient group until a reliable "triage tool" is adopted to pre-select those patients with BNC who will progress or revert to negative.

Cell Nucleus↗
PubMed2001

Hexosamines and nutrient excess induce leptin production and leptin receptor activation in pancreatic islets and clonal beta-cells.

Activation of the hexosamine biosynthesis pathway leads to insulin resistance in muscle and adipose tissue. In these tissues leptin gene expression is increased by glucosamine. In the present study we found that glucosamine rapidly activates the production of leptin and OB-Rb, which encodes the functional leptin receptor, in both primary pancreatic islets and clonal beta-cells. Secretion of leptin from clonal beta-cells into the medium was detected readily. In addition, the level of the transcripts encoding signal transducer and activator of transcription-3 and -5, both implicated in leptin signal transduction in islet beta-cells, was increased by glucosamine, although to a lesser degree than mRNA levels of leptin and OB-Rb. High glucose (16.7 mM) induced leptin biosynthesis in primary pancreatic islet cells, and the addition of 1 mM palmitate caused an additional incremental effect. The hexosamine-mediated induction of the leptin system in clonal beta-cells was associated with increased responsiveness to leptin, as demonstrated by a 2.6 +/- 0.3-fold (P < 0.01) increase in tyrosine phosphorylation of signal transducer and activator of transcription-3. These findings are the first evidence of inducible leptin production in pancreatic islets and suggest that islet cells, like skeletal muscle, demonstrate a linkage between increased nutrient availability and both leptin expression and leptin responsiveness.

Animals↗
PubMed2000

The effects of rexinoids and rosiglitazone on body weight and uncoupling protein isoform expression in the Zucker fa/fa rat.

Agonists for the retinoid X receptor (RXR), the rexinoids, and the peroxisome proliferator-activated receptor gamma (PPARgamma), the thiazolidinediones, are effective in the treatment of insulin resistance in rodent models by enhancing insulin action and improving glycemic control. In the present study, we compared the effects of rexinoids and a thiazolidinedione on body weight and mitochondrial uncoupling protein (UCP) isoform mRNA expression in the obese Zucker fa/fa rat. Long-term (2 weeks) oral treatment with the rexinoids LG100268 and LG100324 reduced food intake and body weight gain, whereas rosiglitazone (BRL49653) tended to increase both food intake and weight gain. LG100268 and LG100324 increased brown adipose tissue (BAT) UCP-1 mRNA content by 2.7-fold (P < .002) and 3.1-fold (P < .001), respectively, while BRL49653 had no effect on BAT UCP-1 mRNA content. Neither the rexinoids nor the thiazolidinedione had any effect on the level of mRNA encoding UCP-2 and the recently described PPARgamma coactivator-1 (PGC-1). LG100324 increased UCP-3 mRNA content by 3.6-fold (P < .0005) in muscle and 4.3-fold (P < .0002) in white adipose tissue (WAT). LG100268 increased UCP-3 mRNA content in WAT by 2-fold (P < .005) but was without any effect on muscle UCP-3. BRL49653 increased UCP-3 mRNA content by 2.1-fold (P < .005) in muscle and 2.7-fold (P < .003) in WAT. Thus, the rexinoids, but not the thiazolidinedione, have an antiobesity action by reducing food intake, and the increase in UCP-1 mRNA content in BAT may reflect a stimulation of BAT UCP-1 activity.

Adipose Tissue, Brown↗
PubMed1998

Do first impressions count? A comparison of subjective and psychologic assessment of spinal patients.

Psychologic factors may have a major influence on the outcome of treatment for back pain. Psychologic disturbance is manifest as emotional distress and may be associated with inappropriate symptoms and signs. Few outcome studies describe the patient population in terms of their psychologic profile. Anecdotal evidence suggested that the routine use of psychologic screening tests in British spine practice was rare. An audit of the prevalent use of psychologic testing amongst a selected group of British spinal surgeons was conducted. This was followed by a prospective, double blind comparison of subjective evaluations of patients with formal psychologic tests. The principal aim was to determine how accurately treating physicians could identify psychologically distressed patients. A postal questionnaire was sent to all consultant members of the British Orthopaedic Spine Society. Details of their current practice and frequency of use of psychologic tests was obtained. In a subsequent study, 125 consecutive new patients attending a back pain clinic were initially evaluated by questionnaires and classified as either psychologically distressed or non-distressed. These patients were then interviewed and examined by treating physicians, who then allocated them to one of four psychologic categories, using predefined criteria. The two results were compared and sensitivity, specificity and predictive values for the subjective evaluations were calculated. Sixty-three percent of respondents to the postal survey either never or only occasionally used any form of psychologic testing in assessing back pain patients. The follow-up prospective study demonstrated that experienced spinal surgeons achieved only a 26% sensitivity when trying to identify distressed patients. The specificity for identifying non-distressed patients was 96%. The predictive value of a "distressed" evaluation was 69%. The predictive value for non-distressed patients was 77%. Subjective psychologic assessment of back pain patients has a low sensitivity and predictive value for distressed patients. Formal psychologic screening should be routinely included in the clinical decision making process.

Attitude of Health Personnel↗
PubMed1998

Osteoblastoma of the vertebral body of the third lumbar vertebra.

The case of a 22-year-old woman presenting with progressive low back pain as a result of a recurrent osteoblastoma of the body of L3, is reported. Total spondylectomy together with anterior and posterior fusion was carried out in a two-stage procedure. We highlight the rarity of the site of occurrence of osteoblastoma, the difficulty in diagnosis and the fact that a radical treatment needs to be performed.

Adult↗
PubMed1997

Mild abnormalities in liver histology associated with chronic hepatitis: distinction from normal liver histology.

BACKGROUND: Chronic hepatitis C virus infection associated with contaminated anti-D immunoglobulin has become an issue of recent concern. The clinical course of chronic hepatitis C infection is unpredictable and histological assessment is felt to be the most reliable means of assessing disease status. Semiquantitative scoring systems have been devised, which assess degree of necroinflammatory disease activity (grade) and extent of disease progression with fibrosis (stage) in chronic hepatitis. Often, using these systems, biopsies of anti-D associated chronic hepatitis C cases show mild changes only, with low scores. The significance of these low scores is uncertain. AIMS: To evaluate the significance of low scores in chronic hepatitis. METHODS: Liver biopsies were assessed from two groups of patients in whom liver histology would be expected to be normal: 30 cases of Gilbert's syndrome and 13 necropsy cases of young people (< 45 years) with no history or risk factors for liver disease. These biopsies were scored using the histological activity index of Knodell et al and its recent modification (separation of scores for grade and stage) by Ishak et al. RESULTS: Twenty of 30 cases of Gilbert's syndrome and 11 of the 13 necropsy cases had chronic hepatitis scores of 1 or 2, whereas only eight cases of Gilbert's and two necropsy cases had scores of 0. The remaining two Gilbert's cases had scores of 3 and 5. Similar results were found using both the histological activity index of Knodell et al and the method of Ishak et al. CONCLUSION: The finding of low but positive scores using these systems in people with normal liver histology questions the reliability and significance of finding such scores in patients with chronic hepatitis and is of particular concern in the evaluation of chronic hepatitis C infection.

Adult↗
PubMed1993

Assessing long term backache after childbirth.

OBJECTIVES: To investigate the factors associated with long term backache after childbirth, to assess all women reporting new onset long term backache, and to investigate any relation with pain relief in labour. DESIGN: Data collected from obstetric records and postal questionnaires or telephone interviews on morbidity after childbirth from all women delivering their first baby between March 1990 and February 1991, followed by analysis of data collected from outpatient consultations. SETTING: St Thomas's Hospital, London. SUBJECTS: Questionnaires were sent to 1615 women who had delivered their first baby in the defined period; 1015 either replied by post or were contacted by telephone. RESULTS: 299 women (29.5% of responders) reported backache lasting more than six months and of these 156 (15.4%) said they had had no back problems previously. Those women who had received epidural analgesia in labour were significantly more likely to report new onset backache (17.8%; 95% confidence interval 14.8% to 20.8%) than those who did not (11.7%; 8.6% to 14.8%). Younger women, unmarried women, and those reporting other antenatal symptoms were significantly more likely to report new long term backache. The 156 women reporting new backache were asked to attend an outpatient clinic and 36 (23%) did so. The majority had a postural backache which was not severe. Psychological factors were present in 14 women. CONCLUSIONS: Though new long term backache is reported more commonly after epidural analgesia in labour, it tends to be postural and not severe. There were no differences in the nature of the backache between those who had or had not received epidural analgesia in labour.

Adult↗
PubMed1993

Malignant pancreatic polypeptide secreting tumour of islet cells: a case for aggressive surgical palliation.

A case of a malignant pancreatic polypeptide secreting tumour is reported. The tumour was metastatic at presentation at which time it was excised. Pancreatic duct obstruction occurred 3 years after excision causing severe pain on eating. Major palliative surgery, in the form of a pancreatico-jejunostomy, cured the severe symptoms. The patient survives, largely symptom free, over six years after original excision. This case illustrates the need for aggressive management of symptoms in tumours in which long term survival is possible despite locally advanced or metastatic disease.

Adult↗
PubMed1990

Malignant sex cord-stromal tumour in a patient with the androgen insensitivity syndrome.

A malignant sex cord-stromal tumour that occurred in a 56-year-old patient with the androgen insensitivity syndrome is reported. Although hamartomas composed of sex cord cells are common in the testes of patients with this syndrome, unequivocal neoplasms of sex cord type are rare. The tumour described herein most closely resembled, but lacked the overall morphology of, a juvenile granulosa cell tumour, and Charcot-Böttcher filaments, indicative of Sertoli cell differentiation, were seen on electron microscopy. The features of the androgen insensitivity syndrome and the various tumours that have been reported in patients with this syndrome are briefly reviewed.

Androgen-Insensitivity Syndrome↗
PubMed1989

Acute mesenteric infarction in elderly patients.

The clinical features, the treatment given, the factors governing treatment selection, and the result of such treatment were analyzed in all patients aged 65 years and over in whom a tissue diagnosis of acute mesenteric infarction was made at a major teaching hospital. Thirty-two such patients, of mean age 78.5 years, were identified during the 8-year study period. Expected clinical features of bowel infarction were commonly absent; for example, there was no abdominal pain and no abdominal tenderness in 29% and 26% of patients, respectively. A sizeable minority of patients (29%) were acutely confused at presentation. All patients not undergoing surgery died shortly after admission to hospital. For those 20 patients (63%) who underwent abdominal surgery, half were discharged alive from hospital. Whether or not the patient survived was associated with the ward to which they were originally admitted. Those admitted to a surgical ward tended to be younger and had a more typical clinical presentation than their counterparts admitted to a medical ward. In particular they were more likely to have abdominal pain and distention and less likely to be confused. Surgical intervention was undertaken more often and earlier in those admitted to surgical wards and this may have accounted for the better outcome. It should be emphasized that acute mesenteric ischemia is a potentially correctable surgical condition even in very elderly people. A realization that the presentation is often atypical should increase the likelihood of early recognition and lead to improved patient survival.

Aged↗
PubMed1988

Progression of dermatofibrosarcoma protuberans to malignant fibrous histiocytoma: report of a case with implications for tumor histogenesis.

A 79-year-old woman required amputation of her left leg for the control of a rapidly growing malignant fibrous histiocytoma. This tumor had developed at the precise site of repeated recurrence of a previously diagnosed dermatofibrosarcoma protuberans. Biopsy specimens from the recurrences revealed a gradual change in appearance from dermatofibrosarcoma protuberans to malignant fibrous histiocytoma.

Aged↗
PubMed1979

The effect of ultrasound on genetic instability in diploids of Aspergillus nidulans.

Ultrasonication at 20 kHz and intensity of 59 W/cm2 of a diploid strain of Aspergillus nidulans was ound to lead to a significant increase in haploidization of germinating conidiospores. In a preliminary study ultrasound was found not to have an effect on the rate of reverse mutation in conidiospore suspensions of auxotrophic mutants.

Aspergillus nidulans↗