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Biomedical subjects

M Besser

Publications and source records attributed to M Besser.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1992

Anaerobic osteomyelitis in patients with Gaucher's disease.

Bone involvement in patients with Gaucher's disease is common, and some of its clinical manifestations may resemble acute osteomyelitis. In addition, many studies have emphasized the high risk of secondary infection when surgical procedures are performed at the site of the involved bone. Nevertheless, these infections have never been well documented in the literature. Presentation of a patient with Gaucher's disease and osteomyelitis due to Prevotella (Bacteroides) melaninogenica provided us the opportunity to review 10 other similar case reports documented in the literature since 1966. This review suggests that acute hematogenic osteomyelitis is an uncommon complication of Gaucher's disease, but it is of interest that in most cases it is due to unusual organisms, particularly anaerobes.

Adult↗
PubMed1992

Controversies in the management of brainstem cavernous angioma: report of two cases.

Two cases of cavernous angioma involving the medulla oblongata are presented. Both cases underwent surgical excision with excellent outcome. The use of surgery via craniectomy is contrasted with stereotactic radiosurgery in light of the known natural history of the lesions. As a result, it is suggested that surgical excision provides immediate protection from the risks of recurrent haemorrhage, establishes a tissue diagnosis, allows complete removal at the primary intervention, avoids complications of radiation-induced damage and is performed more easily in these vascular anomalies due to the presence of a capsule with surrounding gliotic tissue. Additionally, it is implied that the natural history of lesions in this region is still unclear. For these reasons, it is suggested that surgical excision should be the primary therapeutic intervention for cavernous angiomata that involve the brainstem.

Adult↗
PubMed1992

Spinal cord compression in prostate cancer. A 10-year experience.

Of 478 patients treated at a single institution for prostate cancer, 29 developed spinal cord or cauda equina compression. In 5 patients, spinal cord compression was the first evidence of malignancy. Clinical features were predominantly pain, weakness, sensory and sphincter disturbance. The median duration of symptoms was 2 weeks, although the diagnosis was made rapidly at presentation. Clinical diagnosis correlated well with myelographic findings. Only 1 patient suffered neurological deterioration as a consequence of myelography. The functional outcome was dependent on the ability to walk prior to treatment. The median survival in those who were bedridden following treatment was 6 weeks (range 3.5-13) and 21 weeks (range 7-110+) in those who were ambulant following therapy.

Cauda Equina↗
PubMed1992

Interleukin-1 beta and interleukin-6 specifically increase the release of prostaglandin E2 from rat hypothalamic explants in vitro.

It has previously been shown that the cytokines interleukin-1 beta and interleukin-6 (IL-1 beta and IL-6) stimulate directly the release of corticotrophin-releasing-hormone-41 from the rat hypothalamus in vitro, while IL-1 beta can also stimulate the release of somatostatin. These effects can be antagonized by drugs which block prostaglandin (PG) synthesis. PGs are also involved in the control of hypothalamic neuropeptides by other neurotransmitters. In the present study, we have characterized the production of PGs from the rat hypothalamus in vitro, and investigated the effects of IL-1 beta and IL-6, as well as the neurotransmitters norepinephrine, acetylcholine and 5-hydroxytryptamine, on the acute release of PGs, using a well-validated acute hypothalamic incubation system. The rate of release of PGs [PGE2, PGF2 alpha, 6-keto-PGF1 alpha (6KPGF1 alpha) and thromboxane B2 (TXB2) in the medium was found to stabilize after 60 min of preincubation and thereafter remain constant, with TXB2 being the predominant species. Twenty-minute incubation in the presence of human recombinant IL-1 beta or IL-6, in the dose range 1-100 U/ml, had no effect on the release of PGF2 alpha, 6KPGF1 alpha or TXB2; however, the release of PGE2 was significantly increased by both IL-1 beta and IL-6. The effect of IL-1 beta was antagonized by both indomethacin and dexamethasone. None of the other neurotransmitters tested had any effect on the release of any of the PGs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Management of prolactinomas.

The management of prolactinomas requires a complex interaction of medical, surgical and radiotherapeutic intervention. With the judicious use of all these modalities, patients can usually be managed with great success and, perhaps more importantly, their presenting complaints (gonadal dysfunction and infertility) are usually completely corrected.

Bromocriptine↗
PubMed1991

Adrenergic stimulation of the human pituitary-adrenal axis is attenuated by an analog of met-enkephalin.

It has previously been suggested that endogenous opioid peptides may suppress the pituitary-adrenal axis in man by inhibiting an excitatory alpha 1-adrenoceptor input to neural mechanisms liberating corticotrophin-releasing factor or factors (CRFs). This hypothesis has been tested here by investigating the effect of the met-enkephalin analog, DAMME (FK-33,824), on the elevation in serum cortisol induced by the catecholamine-releasing agent d-amphetamine (10 and 25 mg p.o.) and the direct alpha 1-adrenoceptor agonist methoxamine (6 micrograms/kg/min i.v.) in two groups of 6 normal male subjects. In both studies, the rise in serum cortisol was significantly attenuated by the analog of met-enkephalin. These data suggest that exogenous opioids act as a site downstream to the alpha 1-adrenoceptor input to CRF release; it appears that opioids modulate adrenocorticotrophic hormone release in man at a minimum of two distinct and separate sites.

Adrenal Glands↗
PubMed1990

Cushing's disease cycling over ten years.

Cycles of excessive cortisol secretion have been reported interposed with phases of remission lasting from few days to several months. In this study we report a ten year follow up on a patient who had four episodes of hypercortisolism and Cushing's syndrome associated with hypokalemia and edema and three long lasting spontaneous remissions. This was all caused by corticotroph pituitary adenoma. She demonstrated the longest phase of remission yet recorded in this condition, 4.5 years. The precipitating factors for the recurrence in cyclical Cushing's syndrome are not well defined, but the last recurrence in our patient appeared two months after delivery. We have discussed the continuing uncertainty of the standard dynamic tests in the differential diagnosis of Cushing's syndrome.

Adenoma↗