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Biomedical subjects

J V Conaglen

Publications and source records attributed to J V Conaglen.

At least 19 recordsLinked to original sources

An apparently sporadic paraganglioma with an SDHB gene germline mutation presenting at age 68 years.

Paragangliomas (PGLs) are rare tumours arising from parasympathetic-associated paraganglia (particularly of the head and neck) or from sympathetic-associated paraganglia such as in the adrenal medulla when they are termed phaeochromocytomas and at extra-adrenal sites in the abdomen and thorax. Recent reports have found frequent germline mutations of VHL, RET, SDHB or SDHD not only in familial cases but also in apparently sporadic cases of phaeochromocytoma. These germline mutations are particularly likely to be found if multifocal disease is present or if the phaeochromocytoma or PGL occurs at a young age. We report a germline splice site mutation in SDHB in a patient presenting with an incidental, apparently sporadic, abdominal sympathetic PGL at 68 years of age.

Abdominal Neoplasms↗

Burnout in physicians: a case for peer-support.

BACKGROUND: It is well documented that doctors experience a high level of stress in their profession, and that this can lead to physical, psychological, and emotional harm, in particular, burnout. Overseas (especially in the UK and USA), research investigating the levels of stress, burnout, and associated psychiatric morbidity in health professionals, across many specialties, has been carried out with a view to prevention of these adverse outcomes. AIMS: To assess the level of burnout in a sample of New Zealand physicians, the associated work and personal characteristics, and the need for development of a support peer supervision or support system. METHODS: Questionnaires that measured a number of work and personal characteristics, including the Maslach Burnout Inventory, the General Health Questionnaire, and additional questions regarding mistakes, and need for support, were sent to 83 physicians in the Waikato and Bay of Plenty areas. Analysis involved descriptive statistics, with t-tests for comparison with other studies, Pearson Product-Moment correlations between variables and analysis of variance where appropriate. RESULTS: Of the 50 respondents, 28% experienced high levels of two or three aspects of burnout (emotional exhaustion, depersonalization, low personal accomplishment). Emotional exhaustion correlated with a greater need for support. Most respondents favoured a one-to-one support system. CONCLUSION: This study highlights the presence of significant workplace difficulties for physicians and the need to develop a preventative support system for the protection of physicians and the patients in their care.

Adult↗

Cardiac IGF-I manipulation by growth hormone following myocardial infarction.

Evidence of a role for growth hormone (GH) in cardiac structure and function has been derived from studies of patients suffering either GH excess or deficiency, both of which may lead to reduced life expectancy. The role of GH in the ischaemic heart, however, is less than clear. We therefore investigated the effect of 30 days GH treatment in sheep with myocardial infarction. GH treatment significantly increased circulating IGF-I levels (P<0.01), heart weight (P<0.01), and cardiomyocyte cross-sectional area (P<0.001). IGF-I mRNA in peri-infarct cardiac tissue also increased significantly (P<0.05). We conclude that post-infarct GH treatment increases circulating and cardiac IGF-I levels, resulting in significant cardiomyocyte hypertrophy. This increase in cardiomyocyte size appears to correlate with local IGF-I expression rather than plasma IGF-I levels.

Animals↗

A prospective study of the psychological impact on patients of first diagnosis of human papillomavirus.

This study assessed the psychological impact of the first time diagnosis of human papillomavirus (HPV) in consecutive clients attending the Hamilton Sexual Health Clinic, and sought to determine whether this changed over time. Clients with a diagnosis other than HPV and those found to have no diagnosis were compared with HPV clients. All participants completed a battery of questionnaires following their initial visit and again at 4 weeks. The battery consisted of the General Health Questionnaire, Illness Attitude Scales, the International Index of Erectile Function or the Brief Index of Sexual Function for Women, and a 6-question test of the client's knowledge of HPV. One hundred and one participants completed the first questionnaires and 47 of those completed follow-up questionnaires. We found those diagnosed with first episode of HPV had considerable psychological difficulties. However these were no different to those associated with other sexually transmitted infections (STIs) or even those with no active diagnosis.

Adolescent↗

Non-functioning pituitary adenomas: indications for postoperative radiotherapy.

To determine the indications for postoperative radiotherapy after surgical resection of a nonfunctioning pituitary macroadenoma. A retrospective chart review of 72 patients with histologically proven chromophobe adenoma who presented for pituitary surgery between January 1985 and June 1998, with a minimum follow-up period of 12 months. The study endpoint was tumour recurrence or progression detected either by routine follow-up imaging or by clinical progression with subsequent confirmation by imaging. A proportional hazards model was used to determine independent prognostic factors. Mean follow-up was 64 months. In the radiotherapy group 13 of 50 recurred (or progressed) (26%), while in the nonradiotherapy group 10 of 22 recurred (46%), logrank test, P = 0.025. In patients assessed as having complete excision of tumour (n = 20) only two recurred (10%), both in patients without radiotherapy. No further treatment has been required in either case to date. In patients with residual tumour (n = 52), 41 had radiotherapy with 13 recurrences (32%), while 11 patients had no radiotherapy with eight subsequent recurrences (73%); logrank test, P = 0.007. Further treatment has been required in the majority of these cases. Cox's proportional hazards model analysis showed that only complete tumour removal and postoperative radiotherapy were independent favourable prognostic factors. The goal of surgery should be complete surgical excision where possible. The risk of recurrence in patients with no residual tumour on postoperative imaging is low enough to justify withholding routine postoperative radiotherapy in this group. In patients with residual tumour, conventional external beam radiotherapy administered within 12 months of surgery is effective at reducing recurrence or progression.

Adenoma, Chromophobe↗

Myostatin, a transforming growth factor-beta superfamily member, is expressed in heart muscle and is upregulated in cardiomyocytes after infarct.

Myostatin is a secreted growth and differentiating factor (GDF-8) that belongs to the transforming growth factor-beta (TGF-beta) superfamily. Targeted disruption of the myostatin gene in mice and a mutation in the third exon of the myostatin gene in double-muscled Belgian Blue cattle breed result in skeletal muscle hyperplasia. Hence, myostatin has been shown to be involved in the regulation of skeletal muscle mass in both mice and cattle. Previous published reports utilizing Northern hybridization had shown that myostatin expression was seen exclusively in skeletal muscle. A significantly lower level of myostatin mRNA was also reported in adipose tissue. Using a sensitive reverse transcription-polymerase chain reaction (RT-PCR) technique and Western blotting with anti-myostatin antibodies, we show that myostatin mRNA and protein are not restricted to skeletal muscle. We also show that myostatin expression is detected in the muscle of both fetal and adult hearts. Sequence analysis reveals that the Belgian Blue heart myostatin cDNA sequence contains an 11 nucleotide deletion in the third exon that causes a frameshift that eliminates virtually all of the mature, active region of the protein. Anti-myostatin immunostaining on heart sections also demonstrates that myostatin protein is localized in Purkinje fibers and cardiomyocytes in heart tissue. Furthermore, following myocardial infarction, myostatin expression is upregulated in the cardiomyocytes surrounding the infarct area. Given that myostatin is expressed in fetal and adult hearts and that myostatin expression is upregulated in cardiomyocytes after the infarction, myostatin could play an important role in cardiac development and physiology.

Animals↗

Changes in IGFs in cardiac tissue following myocardial infarction.

We have studied changes in the IGF axis in an ovine model of myocardial infarction (MI), in order to determine the relationship between time-based changes in post-infarct myocardium and IGF levels. IGF localization was studied by immunocytochemistry, production by in situ hybridization, and specific binding by radioligand studies. In surviving tissue, IGF-I peptide localized to cardiomyocytes, with strongest immunostaining at 1 and 2 days post-infarct in the immediate border area adjoining the infarct, where IGF-I mRNA also increased, reaching a maximum at 2 days. Binding of radiolabelled IGF-I in surviving tissue was initially lower than that seen in cardiomyocytes in control myocardium, subsequently increasing to become significantly greater by 6 days post-infarct. In necrotic tissue, IGF-I peptide was still detectable in cardiomyocytes at 0.5 days post-infarct, but had cleared from this area by 1 day, becoming detectable again at 6 days post-infarct in macrophages and fibroblasts infiltrating the repair zone. IGF-I mRNA was not detected in necrotic tissue until 6 days, when probe hybridized to macrophages and fibroblasts. Within the necrotic zone, high levels of radiolabelled IGF-I binding to a combination of receptors and binding proteins were observed in cardiomyocytes in islands of viable tissue located close to the border. Weak immunostaining for IGF-II was observed in cardiomyocytes of the surviving tissue. IGF-II mRNA was not detected in either surviving or necrotic areas. Binding of radiolabelled IGF-II was predominantly to macrophages in both surviving and infarct areas, although as with IGF-I, high levels of binding of radiolabelled IGF-II to a combination of receptors and binding proteins were observed in islands of viable tissue close to the border within the necrotic area. We conclude that, following MI, surviving cardiomyocytes at the infarct border show marked changes in IGF-I localization, production, and specific binding, indicating that the IGF axis is directly involved in post-infarct events, possibly in the maintenance of cardiac function by the induction of hypertrophy and in cell survival by decreasing apoptotic cell death, which has been demonstrated in other cell types.

Analysis of Variance↗

Iodine status of New Zealand residents as assessed by urinary iodide excretion and thyroid hormones.

The aims of this study were (1) to compare various measures of I status, and (2) to assess urinary I and thyroid hormone status of residents of two areas of New Zealand where, before the iodization of salt, goitre was endemic due to low soil I. A total of 189 subjects (102 males, eighty-seven females) were recruited from the Dunedin Blood Transfusion Centre, and 144 (sixty-seven males, seventy-seven females) from the Waikato Blood Transfusion Centre between November 1993 and June 1994. Blood was taken for thyroid hormone assays, and subjects collected a fasting overnight urine specimen, a double-voided fasting urine sample, and a complete 24 h specimen for iodide and creatinine analyses. Positive correlations (P < 0.0001) between daily iodide excretion and iodide concentrations in fasting and double-voided fasting urines, identical median values for iodide concentrations in the three samples, and similar numbers of subjects classified as at risk from I deficiency disorders according to the International Committee for the Control of Iodine Deficiency Disorders/World Health Organization categories (World Health Organization, 1994) confirmed indications from earlier studies that fasting urine samples were suitable for population studies. However 24 h urinary iodide excretion remains the recommended measure for individual I status. Waikato residents excreted more iodide in urine and all measures were significantly greater than for Otago residents. However median urinary iodide excretions for both areas (60 and 76 microgram/d for Otago and Waikato respectively) were considerably lower than those reported previously for New Zealand. Thyroid hormone concentrations were within normal ranges. Our findings suggest that I status of New Zealanders may no longer be considered adequate and may once again be approaching levels of intake associated with clinical I deficiency.

Adolescent↗

Laparoscopic retroperitoneal left adrenalectomy in a patient with Cushing's syndrome.

A technique for the extraperitoneal removal of the adrenal gland using laparoscopic instrumentation and insufflation is described. A case of Cushing's syndrome in a 42 year old female is presented with successful removal of her adrenal tumour using the laparoscopic method. This is the first report of laparoscopic adrenalectomy employing the extraperitoneal approach.

Adrenalectomy↗

Effect of long-term inhibition of gonadotrophin secretion by the gonadotrophin-releasing hormone agonist, buserelin, on sex steroid secretion and ovarian morphology in polycystic ovary syndrome.

In order to investigate the effect of long-term suppression of the gonadotrophin axis in polycystic ovary syndrome, eight affected subjects were given s.c. infusions of gonadotrophin-releasing hormone (GnRH) agonist buserelin for 12 weeks. Hormone measurement and ultrasound studies were carried out weekly, from 6 weeks before to 12 weeks after administration of buserelin. An overnight dexamethasone-suppression test was carried out before and after treatment. Maximal suppression of LH to below the lower limit of that in normal subjects occurred after 6 weeks of treatment with buserelin. Plasma testosterone and androstenedione fell to normal levels during the infusion but reached pretreatment levels during the follow-up period. There was no effect of buserelin on plasma dehydroepiandrosterone sulphate or sex hormone-binding globulin. Ovarian size decreased significantly during the infusion with the disappearance of cysts in six subjects. After cessation of buserelin therapy, there was rapid and spontaneous ovulation which occurred within 3 weeks in all subjects. The results suggest that treatment with this GnRH agonist facilitates ovulation in this condition.

Adult↗

Effect of melatonin on jet lag after long haul flights.

OBJECTIVE: To determine whether doses of the pineal hormone melatonin alleviate jet lag. DESIGN: Double blind, placebo controlled crossover trial. SETTING: Long haul return flights from Auckland, New Zealand, to London and back. SUBJECTS: Twenty volunteers with experience of transcontinental flights (eight women and 12 men aged 28 to 68). INTERVENTIONS: Melatonin (or placebo) 5 mg three days before flight, during flight, and once a day for three days after arrival. END POINT: Symptoms of jet lag. MEASUREMENTS AND MAIN RESULTS: Visual analogue scale for feelings of jet lag and tiredness; profile of moods states questionnaire for vigour-activity and fatigue-inertia; and retrospective ratings 10 days after arrival of sleep pattern, energy, and daytime tiredness. Feelings of jet lag were less for subjects taking melatonin (mean score 2.15 v 3.4); these subjects took fewer days than the placebo group to establish a normal sleep pattern (2.85 v 4.15), to not feel tired during the day (3.0 v 4.6), and to reach normal energy levels (3.25 v 4.7). Results for fatigue-inertia and vigour-activity were similar. For all subjects jet lag was more severe on the return (westward) than the outward (eastward) journey. CONCLUSIONS: Melatonin can alleviate jet lag and tiredness after long haul flights.

Adult↗

The effect of a high protein diet on leucine and alanine turnover in acid maltase deficiency.

Leucine and alanine production rate was measured in 5 patients with acid maltase deficiency in the postabsorptive state, following 6 months on a normal diet with placebo and 6 months on an isocaloric high protein diet (16-22% protein). Whole body leucine production rate, a measure of protein degradation, expressed in terms of lean body mass was significantly greater than in five control subjects. Following the high protein diet, leucine production rate was decreased in four of the five patients but this was not statistically significant. Alanine production rate expressed in terms of lean body mass was significantly greater than in control subjects. After the high protein diet, alanine production rate and concentration were significantly decreased (p less than 0.05). There were no significant improvements in any of the clinically relevant variables measured in these patients. It is possible that a larger increase in protein intake over a longer time period may have a clinical effect.

Adult↗

Effect of stilboestrol on sodium balance, cardiac state, and renin-angiotensin-aldosterone activity in prostatic carcinoma.

A prospective study examined the sequential effects of diethylstilboestrol (stilboestrol) on sodium balance, cardiac state, and renin-angiotensin-aldosterone activity in six patients with metastatic carcinoma of the prostate. Whereas metabolic balance studies did not show evidence of sodium retention during the first seven days of treatment, there was a significant and progressive increase in plasma volume after three months (mean increase 541 ml; p less than 0.01). Stilboestrol increased supine plasma renin and angiotensin II values but the response of renin-angiotensin-aldosterone activity to erect posture was progressively reduced during treatment. No significant changes in blood pressure or indices of cardiac function occurred during the three months of observation. The findings of increased basal renin-angiotensin-aldosterone activity and an increase in plasma volume suggest an important mechanism of the cardiac complications associated with oestrogen treatment.

Aged↗

Augmentation of the response to CRF in man: relative contributions of endogenous angiotensin and vasopressin.

The plasma ACTH response to corticotrophin releasing factor (CRF) was studied in seven normal individuals. Five subjects were restudied following 4 d of salt restriction which resulted in raised endogenous plasma angiotensin II secretion. In a third experiment six subjects were given CRF following pre-infusion of hypertonic saline which significantly increased endogenous plasma vasopressin (AVP) levels. We were unable to demonstrate that high endogenous plasma AII levels were associated with a significant change in the plasma ACTH or cortisol responses to CRF. However there was an almost three-fold increase in the ACTH response when endogenous plasma AVP was elevated by hypertonic saline. It is concluded that AVP is likely to be of physiological importance in potentiating the ACTH response to CRF and that AVP and CRF together may provide a better test of pituitary ACTH secretion than either peptide alone.

Adrenocorticotropic Hormone↗