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Biomedical subjects

M Besser

Publications and source records attributed to M Besser.

At least 19 recordsLinked to original sources
PubMed1997

Competency-based learning in traumatology.

BACKGROUND: A multidisciplinary, competency-based trauma teaching program was introduced for final year medical students (n = 67) at Royal Prince Alfred Hospital (RPAH) in 1994 to complement the surgical clerkship. METHODS: The method involved small groups rotating through a series of teaching stations each structured to address a predetermined competency. Four 3-hour sessions were held on the subject areas of resuscitation, plastic, orthopedic, and neurotrauma. Performance in the trauma section of a summative Objective Structured Clinical Examination (OSCE), 6 months after the teaching, was compared with that of a control group (n = 127) from other campuses where trauma was taught by a series of discipline-based lectures. Three trauma OSCE stations were designed to test psychomotor skills while five addressed aspects of the cognitive domain. Checklists were used to ensure standardization of scoring in a range of questions asked for skills tested at each station. RESULTS: The marks of the RPAH students (mean 78% +/- SD 9%) were significantly higher (P < 0.0005) than the controls (mean 70% +/- SD 9%) in the 8 trauma questions. There was no significant difference (P = 0.8) in marks obtained by the study group (mean 61% +/- SD 8%) and controls (mean 63% +/- SD 7%) in 22 questions sampling a wide spectrum of nontrauma subject areas. The study group performed significantly better in one of the three skills stations and three of the five problem-solving stations when compared with the control group. CONCLUSION: The innovation has the potential to fulfill a need for an integrated trauma program in the undergraduate core curriculum.

Australia↗
PubMed1997

Acromegaly, colonic polyps and carcinoma.

OBJECTIVE: It has been suggested that patients with acromegaly may be at risk of developing colorectal carcinoma. In order to clarify this issue, we have evaluated the prevalence of carcinoma, premalignant tubulovillous adenomas and hyperplastic colonic polyps in a large cohort of patients with acromegaly. DESIGN: Prospective colonoscopic examination by a single operator. PATIENTS: One hundred and twenty-nine patients with biochemically proven acromegaly. RESULTS: At least one lesion was visualized in 63 patients. Adenocarcinoma was present in six patients (5%), but only two had symptoms; all lesions were endoscopically obvious. Compared with a normal group, the odds ratio of colorectal cancer is increased at 13.5 (95% confidence intervals (c.i.) 3.1-75). One or more tubulovillous adenoma was found in 34 patients (26%) and this prevalence was age-dependent, occurring in 39% of patients aged 70 years or over. Comparing the prevalence of left-sided colonic adenomas with that in a normal group, there is a higher prevalence among patients over 49 years with an odds ratio of 4.2 (95% c.i. 2.5-6.8). Patients with acromegaly who had an adenoma were significantly older than unaffected patients (61.9 vs 54.1 years; P < 0.001) but had similar GH and IGF-1 levels and duration of disease. CONCLUSIONS: Patients with acromegaly have an increased risk of developing colorectal cancer and a significantly higher prevalence of tubulovillous adenomas compared with normal subjects. Routine surveillance colonoscopy is indicated in this group of patients.

Acromegaly↗
PubMed1997

Pheochromocytoma: effect of nonionic contrast medium in CT on circulating catecholamine levels.

PURPOSE: To study the catecholamine-releasing effect of peripheral intravenous administration of the nonionic contrast medium iohexol in patients with pheochromocytomas. MATERIALS AND METHODS: Ten patients (eight women, two men; mean age, 44 years; age range, 25-70 years) with pheochromocytomas and related tumors and six healthy volunteers (five men, one woman; mean age, 31 years; age range, 27-35 years) were examined. Plasma catecholamine levels were measured at intervals for 60 minutes after the injection of 0.9% saline or iohexol on 2 separate days. All 10 patients intravenously received the specific alpha-adrenergic blocker phenoxybenzamine hydrochloride (0.5 mg/kg in 250 mL of 5% dextrose infused over 2 hours) 24 hours before iohexol-enhanced computed tomography. RESULTS: There was no statistically significant increase in epinephrine or norepinephrine levels in the patients or the control subjects. CONCLUSION: While it may be prudent to administer oral alpha- and beta-adrenoceptor antagonists in all patients with a biochemically proved pheochromocytoma to control their symptoms and to prevent a spontaneous adrenergic crisis, specific blockade may not be required before contrast medium-enhanced scanning with iohexol. Although the sample size of this study is relatively small, the results do suggest that in an incidentally detected, clinically silent adrenal mass that may or may not be hypersecreting, the nonionic contrast medium iohexol may be used for scanning without blockade.

Adrenal Gland Neoplasms↗
PubMed1997

A combined test using desmopressin and corticotropin-releasing hormone in the differential diagnosis of Cushing's syndrome.

To assess the ability of desmopressin to differentiate between pituitary and ectopic ACTH-dependent Cushing's syndrome and to determine whether diagnostic accuracy could be improved by administering it together with human sequence CRH, we examined its effects on cortisol and ACTH secretion when given alone or in combination with CRH in patients with Cushing's syndrome of varied etiology and compared these data to the results of a standard CRH test in the same individuals. Each patient was studied on three occasions, in random order, separated by at least 48 h. At 0900 h, via an indwelling forearm cannula, 10 micrograms desmopressin, 100 micrograms CRH, or a combination of the two were given as an iv bolus; thereafter, blood was drawn every 15 min for 2 h. The responses to the individual agents were determined according to the timing and calculation criteria suggested by Nieman et al. (1993). A total of 25 patients with Cushing's syndrome were studied: 17 patients with pituitary-dependent Cushing's syndrome, Cushing's disease (CD); 5 patients with occult ectopic ACTH secretion (EC); and 3 patients with primary adrenal (ACTH-independent) Cushing's syndrome. In this series, the best discrimination among ACTH-dependent patient groups was achieved using the combined test. Using the responses of plasma cortisol, all 17 patients with CD showed a rise greater than any of the 5 patients with EC, whereas 1 patient with CD showed a plasma ACTH response within the range seen in the patients with EC. Plasma cortisol responses to desmopressin alone were seen in 14 of 17 patients with CD and 1 of 5 patients with EC and, after CRH alone, in 15 of 17 patients with CD but in no patient with EC. In contrast, plasma ACTH responses after CRH alone were seen in 14 of 17 patients with CD and 2 of 5 patients with EC and, after desmopressin alone, in 12 of 17 with CD and 3 of 5 with EC, thus indicating overlapping responses between the groups and poorer discrimination. No responses were seen in the ACTH-independent group. These data indicate that desmopressin causes the secretion of ACTH and cortisol in patients with ACTH-dependent Cushing's syndrome, and that in combination with CRH, it may provide an improvement over the standard CRH test in the differential diagnosis of ACTH-dependent Cushing's syndrome. Furthermore, these data suggest that there may be abnormalities in vasopressin receptor function or number in ACTH-secreting tumors.

ACTH Syndrome, Ectopic↗
PubMed1996

The acute cardiovascular actions of intravenous thyrotrophin releasing hormone (TRH) in man are mediated by non-catecholaminergic mechanisms.

1. Intravenous bolus doses of thyrotrophin releasing hormone (TRH, 50-1000 micrograms) caused statistically significant, non-dose dependent and transient rises in blood pressure, heart rate and plasma catecholamines in healthy young males. 2. Mean peak incremental rises in systolic blood pressure (mean +/- s.e. mean) following 50, 200 and 500 micrograms TRH were 14.3 +/- 2.9 mmHg, 15.7 +/- 3.2 mmHg and 17.1 +/- 3.9 mmHg respectively (all P < 0.05 vs placebo). Mean incremental rises in heart rate for the three doses of TRH were 8.2 +/- 2.2 beats min-1, 7.1 +/- 1.8 beats min-1, and 10.7 +/- 2.9 beats min-1 respectively (all P < 0.05 vs placebo). 3. Following the 50 micrograms and 1000 micrograms doses of TRH, plasma noradrenaline and adrenaline rose significantly (P < 0.05) between 4 and 8 min. Mean +/- s.e. mean incremental plasma noradrenaline rise following 50, 200 and 100 micrograms TRH were 0.4 +/- 0.13 nmol 1(-1), 0.37 +/- 0.21 nmol 1(-1) and 0.41 +/- 0.18 nmol 1(-1) respectively. Mean +/- s.e. mean incremental rise in adrenaline for the 50, 200 and 1000 micrograms dose were 0.13 +/- 0.04 nmol 1(-), 0.08 +/- 0.03 nmol 1(-1), and 0.11 +/- 0.05 nmol 1(-1) respectively. 4. Following administration of the ganglion blocking drug pentolinium (5 mg) the incremental systolic blood pressure and heart rate rises following 500 micrograms TRH alone 16.6 +/- 2.8 mmHg and 10.4 + 3.1 beats min-1 respectively. 5. The rises in plasma noradrenaline and adrenaline following TRH were attenuated by prior ganglion blockade. 6. alpha-Adrenoceptor blockade with thymoxamine (0.3 mg kg-1 bolus + 0.3 mg kg-1 h-1 infusion), singly and combined with intravenous propranolol (10 mg i.v. over 10 min), did not alter the pressor or tachycardic effects of 500 micrograms TRH. 7. In conclusion, although plasma noradrenaline rises following i.v. TRH, suggesting activation of the sympathetic nervous system, this effect is not responsible for the pressor response to TRH, which appears to be due to either a direct vasoconstrictive effect on the peripheral resistance vessels or a direct inotropic/chronotropic effect on the heart.

Adrenergic Antagonists↗
PubMed1996

Assessment of cure after transsphenoidal surgery for Cushing's disease.

The best long-term results of transsphenoidal surgery appear to be in those patients who have unmeasurable serum cortisol levels in the immediate post-operative period. This appears to be due to isolated ACTH deficiency in the remaining normal pituitary gland. In our experience, however, long-term clinical remission may be possible with measurable serum cortisol levels post-operatively. The cortisol response to ACTH or CRF appears to provide no greater discrimination than basal measurements and is possibly less helpful than dexamethasone suppression. The prolonged clinical remission that we have seen in some patients with early measurable but low cortisol levels, together with the possible operative morbidity and partial success of repeat surgery, suggests careful assessment before a recommendation is made of an immediate second operation in these patients. The possibility of cyclical secretion of cortisol must be considered both pre and post-operatively. Finally, as experience with transsphenoidal surgery is still relatively short, all these patients need continuing endocrine follow-up in centres with adequate experience of the condition. For the individual patient we recommend that decisions regarding further therapy are based on 0800-0900 h serum cortisol levels, an index of cortisol production (serum cortisol day profiles or 24 hour urinary free cortisol), and the response to low dose dexamethasone suppression in the early post-operative period.

Cushing Syndrome↗
PubMed1996

Diagnosis of growth hormone deficiency in adults.

The potential effects of growth hormone (GH) deficiency in adults and the importance of GH secretion in adult life have only been recognized and documented recently. It has been suggested that GH-deficient adults may have premature mortality, abnormalities in body composition and bone density with impaired physical performance and psychological well-being, which are sometimes improved by GH replacement. It is essential, therefore, to establish reliable standards to define GH deficiency in adults. Patients with possible GH deficiency often have primary pituitary or hypothalamic disorders or have undergone surgery or radiotherapy, and thus show evidence of a failure of one of the other pituitary hormones. Several biochemical approaches have been studied to define GH deficiency in the adult and no universal consensus has yet been reached. The most widely established criterion is the peak serum GH concentration achieved during a provocative test, usually the insulin tolerance test (ITT), or following other pharmacological stimuli (e.g. glucagon, arginine, clonidine or GH-releasing factor) but, alternatively, a more physiological stimulus (such as sleep, fasting or exercise) has been used. Spontaneous circulating levels of hormones of the GH axis [24-hour integrated GH concentration, serum insulin-like growth factor I (IGF-I) or IGF-binding protein-3] have been used in the diagnosis of childhood GH deficiency. They have been tested in adults as well but seem to have a more limited role. There are several factors complicating the evaluation of these results. Basal and stimulated GH and IGF-I levels decline with age and with obesity, levels tend to be higher in females and are dependent on nutritional and physical status. The ITT potentially has some risk attached, e.g. in the presence of ischaemic heart disease, but it has proved to be safe in general when used in specialized departments. Other tests are less reliable; releasing hormone tests only assess the readily releasable stores within the pituitary and not the physiological secretory status. The 'cut-off' point for the definition of subnormal responses ideally needs to be set for each provocative test, for each age group, for each degree of obesity and for both sexes. There is considerable variability in GH assays among different laboratories, which makes it difficult to compare hormone levels. The reproducibility of provocative tests can also be variable. An advantage of the hypoglycaemia and glucagon tests is that they allow simultaneous assessment of the adrenocorticotropic hormone reserve.

Adult↗
PubMed1996

L-arginine is unlikely to exert neuroendocrine effects in humans via the generation of nitric oxide.

There is now considerable evidence that nitric oxide is an important neuroregulatory agent, but there has been very little investigation of its possible role in neuroendocrine mechanisms in humans. We have investigated the effects of two nitric oxide precursors, L-arginine and molsidomine, under basal conditions on the pituitary hormones growth hormone (GH), prolactin, luteinizing hormone, follicle-stimulating hormone, thyrotrophin, adrenocorticotrophin (ACTH) and vasopressin, and also on serum cortisol; we have also studied the effect of L-arginine on circulating prolactin, ACTH and cortisol in normal human subjects under hypoglycaemic stress. L-Arginine stimulated both GH and prolactin release under basal conditions but had no effect on the other hormones studied, while the nitric oxide donor molsidomine showed no effect on any hormone studied. L-Arginine potentiated the hypoglycaemia-stimulated release of ACTH but did not influence the rise in GH. The current studies suggest that the effects of L-arginine on the stimulation of GH and prolactin release are unlikely to be mediated via the generation of nitric oxide.

Adrenocorticotropic Hormone↗
PubMed1995

A single sleeping midnight cortisol has 100% sensitivity for the diagnosis of Cushing's syndrome.

OBJECTIVE: The diagnosis of Cushing's syndrome remains a major challenge in clinical endocrinology. Various screening tests are commonly used to support a biochemical diagnosis in the context of clinical suspicion. The aim of this study was to compare the sensitivity in the diagnosis of Cushing's syndrome of a single in-patient sleeping midnight cortisol to a standard 48-hour in-patient low-dose dexamethasone suppression test (LDDST) during the same admission. DESIGN: A retrospective analysis was performed on 150 patients investigated in our department between the years 1970 and 1994 with a confirmed diagnosis of Cushing's syndrome. PATIENTS: One hundred and fifty patients with a diagnosis of Cushing's syndrome were analysed: 110 with Cushing's disease; 12 with tumours with ectopic ACTH secretion; 8 with ACTH dependent Cushing's syndrome of so far undetermined origin; 17 with cortisol secreting adrenal tumours; 3 with adrenocortical nodular hyperplasia. Twenty normal volunteers and nine patients with non-endocrine conditions were also investigated as controls. MEASUREMENTS: Plasma cortisol was measured by radioimmunoassay (RIA) in the 122 patients presenting after 1980, and by fluorimetry prior to this date. RESULTS: In all the control subjects the sleeping midnight cortisol was < 50 nmol/l, below the lowest standard of the routine in-house RIA. In every patient with Cushing's syndrome the sleeping midnight cortisol was detectable with a value greater than 50 nmol/l, with a range of 70-2000 nmol/l. In contrast, in three cases, all of whom had proven Cushing's disease on histology, there was uncharacteristic complete suppression of plasma cortisol to < 50 nmol/l following the LDDST. CONCLUSION: In this series of 150 cases, a single in-patient sleeping midnight cortisol above 50 nmol/l had a 100% sensitivity for the diagnosis of Cushing's syndrome, clearly different from normal subjects. In contrast, the low-dose dexamethasone suppression test had a sensitivity of 98% even when the drug was administered as an in-patient. We recommend that a low-dose dexamethasone suppression test should not be used alone for confirmation of Cushing's syndrome since it may miss 2% of cases.

Adolescent↗
PubMed1995

Outcome of patients with neurotrauma: the effect of a regionalized trauma system.

A system of regionalized trauma care was introduced to Sydney in early 1992. This study was carried out to assess the effect of regionalization on the outcome of patients suffering major head injury within the central Sydney area. A prospective before and after study extending over 3 years and centred on the time of designation of Royal Prince Alfred Hospital (RPAH) as a trauma centre, was the methodology used. The study group consisted of all patients admitted with head injury (Glasgow Coma Score < 9; admission systolic blood pressure > 90 mmHg; Injury Severity Score > 15) to RPAH from the central Sydney area. Outcome criteria include survival rates, transfer numbers, and time to definitive neurosurgical care. Fifty patients were entered during the first 18 months of the study, and 38 during the second 18 months. Fifteen in the first group required evacuation of intracranial mass lesions, as did nine in the second group. The overall mortality fell from 42 to 26% (P = 0.13). During the study period there were 77 primary retrievals and 20 required evacuation of mass lesions. The median time from injury to commencement of operation in these patients was 2 h 13 min (range 1 h 3 min-5 h 35 min). There were 11 transfers, four requiring craniotomy. The median time from injury to surgery was 7 h 24 min (range 3 h 2 min-10 h 25 min; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Cushing's syndrome. Therapy directed at the adrenal glands.

Establishing the exact etiologic diagnosis of Cushing's syndrome is fundamental to the management of the disease. It allows for specific therapy, such as pituitary microsurgery. In cases where the adrenal gland is the cause, treatment can be either surgical or medical. This article explores both types of treatment and their respective results.

Adenoma↗
PubMed1993

Nitric oxide modulates the release of corticotropin-releasing hormone from the rat hypothalamus in vitro.

There is now considerable evidence that nitric oxide (NO) is an important neuroregulatory agent, but there has been very little investigation of the possible role of NO in neuroendocrine mechanisms. We have previously shown that acute rat hypothalamic explants can be used to study the regulation of hypothalamic neuropeptide release, and we have now utilised this experimental approach to investigate the putative involvement of NO in the control of the principal corticotropin-releasing hormone, CRH. We studied the direct effects of the NO precursor L-arginine (L-ARG), as well as the NO donors molsidomine and sodium nitroprusside, on both the basal and stimulated release of CRH; the stimuli used were non-specific depolarisation with potassium chloride (KCl) and the specific cytokine, interleukin-1 beta (IL-1 beta; 100 U/ml). L-ARG was tested in each experimental condition with and without contemporaneous addition of its competitive antagonist NG-monomethyl-L-arginine (L-NMMA). IL-1 beta-induced CRH release was also investigated in the presence of D-arginine (D-ARG), which is not active as a precursor to NO, and ferrous hemoglobin (Hb), a substance which is a potent inactivator of NO. None of the NO precursors (L-ARG, molsidomine, sodium nitroprusside) or antagonists (L-NMMA or Hb) was able to affect basal CRH release. However, L-ARG 10 and 100 microM were found to significantly inhibit the release of CRH induced by 40 mM KCl; CRH fell to 45% of its stimulated level at the higher dose of L-ARG. This effect was attenuated in the presence of L-NMMA at a ten-fold higher dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Criteria for medical as opposed to surgical treatment of prolactinomas.

The treatments for both true and pseudoprolactinomas are reviewed. True prolactinomas, usually characterized by pituitary lesions and circulating levels of prolactin in excess of 2 U/l (100 micrograms/l), are best treated with a dopamine agonist such as bromocriptine. Administration of 50 mg of a repeatable bromocriptine depot preparation (Parlodel-LAR, Sandoz, Basel, Switzerland), results in a prompt reduction of circulating prolactin levels to within normal limits over 48 h in a patient with macroadenoma. Bromocriptine treatment results in a reduction of circulating prolactin in 80% of patients and tumour shrinkage in about two-thirds. Patients with macroadenomas treated successfully with dopamine agonists should be given pituitary radiotherapy to provide long-term ablation of the prolactin-secreting cells and facilitate a gradual cessation of drug. Tumours which are not responsive to dopamine agonists should undergo trans-sphenoidal surgery. Pseudoprolactinomas usually associated with circulating prolactin levels < 2 U/l (100 micrograms/l) are caused by a peripituitary tumour which obstructs the flow of dopamine into the pituitary. Treatment with dopamine agonists reduces prolactin levels but does not result in tumour shrinkage and so the treatment of choice is trans-sphenoidal surgery. Surgery is also indicated in patients with intolerance to dopamine agonists.

Dopamine Agents↗
PubMed1992

Pseudotumor syndrome in treated arachnoid cysts.

We report three patients with arachnoid cysts treated by cyst-peritoneal shunting in whom intracranial hypertension occurred during episodes of shunt malfunction. In one case this was associated with re-expansion of the arachnoid cyst, whilst in the other two cases this did not occur. The similarities between these two cases and patients with pseudotumor cerebri suggest a common pathogenic mechanism--specifically, a disturbance of the cerebrospinal fluid circulation.

Arachnoid Cysts↗