PubMed HealthSearch

Biomedical subjects

L Lazarus

Publications and source records attributed to L Lazarus.

At least 19 recordsLinked to original sources

The impact of recent advances in diagnostic technology on the clinical presentation of phaeochromocytoma.

OBJECTIVE: To examine the impact of recent advances in diagnostic technology on the spectrum of clinical and biochemical features of patients presenting with a new diagnosis of phaeochromocytoma. DESIGN: A retrospective review of the clinical and biochemical features of patients diagnosed by our laboratory as having phaeochromocytoma within a 27-month period up to December, 1990. Noradrenaline, adrenaline and dihydroxyphenylglycol were assayed in 24-hour urine specimens (19 patients) or plasma (1 anuric patient) by gas chromatography/mass spectrometry. SETTING: A tertiary level chemical pathology department. PATIENTS: Twenty patients with a new diagnosis of phaeochromocytoma. RESULTS: The classic, episodic adrenergic symptoms traditionally associated with phaeochromocytoma were absent in 9 of the 20 patients (45%). "Atypical" phaeochromocytoma presented as a mass on computed tomography imaging (6 patients, 30%), "phaeochromocytoma crisis" (4 patients, 20%) or family screening (1 patient, 5%). Excessive adrenaline production was found in 11 patients (55%) and six (30%) had predominantly adrenaline-secreting tumours. The urinary noradrenaline:dihydroxyphenylglycol ratio was raised in all nine patients with predominantly noradrenaline-secreting tumours but was not raised in nine out of ten patients with adrenaline-secreting phaeochromocytoma. Adrenaline excretion was significantly correlated with tumour size (r = 0.8; P less than 0.05). CONCLUSIONS: Advances in diagnostic technology, particularly specific adrenaline assays and computed tomography, have made possible the early diagnosis of patients with phaeochromocytoma presenting in ways previously thought to be uncommon. All patients with adrenal masses noted incidentally on CT scan should be investigated for phaeochromocytoma. Adrenaline-secreting tumours are common and both noradrenaline and adrenaline should be assayed in all patients investigated for phaeochromocytoma.

Adrenal Gland Neoplasms

Biochemical diagnosis of pheochromocytoma by simultaneous measurement of urinary excretion of epinephrine and norepinephrine.

The utility of specific assay of urinary catechols in pheochromocytoma diagnosis was examined by reviewing our data on the investigation of pheochromocytoma in a population of 2476 patients investigated over a six-year period. We used specific gas-chromatographic/mass-spectrometric (GC/MS) analysis for the simultaneous measurement of norepinephrine, dopamine, and the neuronal metabolites 3,4-dihydroxyphenylglycol (DHPG) and 3,4-dihydroxyphenylacetic acid (DOPAC) in all samples; the last two years of data collection (from 1101 patients) also included the specific GC/MS assay of epinephrine. The importance of assaying epinephrine as well as norepinephrine was shown by these latter data. During this latter period, 19 of 1101 patients were found to have pheochromocytoma; of these, nine had tumors that exclusively secreted norepinephrine, six had tumors that exclusively secreted epinephrine, and four exhibited excess production of both norepinephrine and epinephrine. Neither dopamine nor DOPAC was useful in the diagnosis of pheochromocytoma. A substantial proportion of patients may have uniquely epinephrine-secreting pheochromocytomas, previously considered a rarity. Thus we recommend that the biochemical testing for pheochromocytoma include the specific measurement of both norepinephrine and epinephrine.

3,4-Dihydroxyphenylacetic Acid

Acute effects of lithium on central dopamine and serotonin activity reflected by inhibition of prolactin and growth hormone secretion in the rat.

The acute administration of lithium chloride significantly inhibits both prolactin and growth hormone secretion in the rat. In terms of known neuroendocrine relationships this finding indicates that lithium administration alters both dopamine (DA) and serotonin (5-HT) activity in the hypothalamus. The data suggest that DA activity is increased (inhibiting prolactin release) and 5-HT activity is decreased (reducing growth hormone stimulation). The data are in agreement with fluorescent histological studies on the effects of chronic lithium administration and suggest that endocrine parameters may be used to provide neuropharmacological information about compounds which alter brain monoamine activity.

Animals

A simple procedure for the assay of brain biogenic amines by selected-ion monitoring: its application to the elucidation of the mechanism of prolactin release induced by 3-iodo-L-tyrosine.

A simple method for the assay of brain biogenic amines by selected-ion monitoring was applied to examination of the effects of 3-iodo-L-tyrosine on the hypothalamic-median eminence concentrations of dopamine, noradrenaline and serotonin in the rat. Thirty minutes after its administration iodotyrosine (50 mg/kg) caused a highly significant (P less than 0.0005) rise in serum prolactin and a highly significant (P less than 0.0025) fall in the concentration of dopamine in the hypothalamus and median eminence where the levels reached 50% of control levels. Less marked but significant falls were also observed in the hypothalamic (P less than 0.05) and median eminence (P less than 0.0025) concentrations of noradrenaline after iodotyrosine administration. Serotonin concentration was significantly reduced (P less than 0.025) in the median eminence but not in the hypothalamus after iodotyrosine administration. These findings suggest that iodotyrosine exerts its prolactin stimulating effect by blockage of dopamine synthesis rather than by receptor blockade.

Animals

Acromegaly.

Explore the source record for details and available documents.

Acromegaly

Immune complexes in diabetes mellitus.

Sera from 86 well controlled diabetics were examined for the presence of immune complexes. Thirty-six patients were receiving standard insulins, 19 monocomponent preparations, 24 oral hypoglycaemic agents and seven dietary restriction alone. Three methods were used to detect complexes: measurement of complement components, a Clq binding assay (BA) and the Raji cell radioimmunoassay (RIA). Complement components were normal in all patients. Eleven (31%) of the group on standard insulins had a positive Raji cell RIA; none had an abnormal Clq-BA. One patient on monocomponent therapy had a mildly positive Raji cell RIA; Clq-BA was negative in each patient of this group. Thirteen (54%) of the patients on oral hypoglycaemic agents were positive on one or both assays while one patient on diet alone was abnormal on both assays. These data show that immune complex production is common in both insulin-requiring and non-insulin-requiring diabetics and that this phenomenon is strikingly less frequent in patients on monocomponent insulins. Such observations could bear relevance to the pathogenesis of microvascular complications in diabetes.

Adolescent

Release of secretin--plasma levels reproduced by exogenous infusion.

Infusion of 0.1 M HCl (0.5 mmol/kg/hr over 20 minutes) into the duodenum of each of seven normal subjects led to a significant rise (P less than 0.05) in mean plasma secretion levels from 3.0 +/- 2.2 (SE) to 15 +/- 4.0 pmol/l. Intravenous infusion of secretin at a rate of 6.6 pmol/kg/hr (0.08 clinical units/kg/hr) reproduced the peak plasma levels of secretin observed during duodenal acidification. However, there was no detectable (2.5 pmol/l) change in plasma secretin after oral protein or glucose.

Duodenum

Development of a closed-loop artificial pancreas.

A closed-loop glucose controlled insulin infusion system was developed, consisting of elements for continuous blood glucose analysis, a computer control system, and infusion systems. Improvements include decreased size, cost reduction and better performance. The algorithm used was a piecewise linear representation of the sigmoidal curve commonly employed. The apparatus has been applied to simulation of the healthy beta cell and glucose clamp studies.

Artificial Organs

Circulating thyroid hormone levels and adequacy of dialysis.

In vitro thyroid function tests were performed in three groups of patients with chronic renal failure who were receiving, on average, 15, 18 and 27 hours of maintenance hemodialysis per week. Total thyroxine levels were low and total triiodothyronine levels low to normal in those receiving the least dialysis (15 hours), and were significantly higher in those receiving longer dialysis. Free thyroxine levels, as measured by the effective thyroxine ratio, were normal and similar in all three groups, as were serum thyrotrophin levels. All patients were clinically euthyroid. As total hormone levels showed a significant inverse relationship to both urea and creatinine, this study suggests that there is a dialyzable metabolite retained in uremia which competes with thyroid hormones for protein-binding sites.

Adult

Defective blood glucose counter-regulation in diabetics is a selective form of autonomic neuropathy.

Administration of a low-dose insulin infusion to normal subjects results in a mild drop in blood glucose concentration (1.1 mmol/1 (20 mg/100 ml)) and the resetting of the basal glucose at the lower concentration. Clinical hypoglycaemia does not develop, and there is a significant release of glucagon, growth hormone, and cortisol. A similar infusion in insulin-requiring diabetics results in hypoglycaemia accompanied by a release of growth hormone and cortisol but no significant release of glucagon. Subsequently giving arginine to these patients results in a significant release of glucagon, indicating that the alpha cell is intact and can respond to local, direct stimulation. In one patient the defect in glucagon response to impending hypoglycaemia developed after two years' insulin treatment. This type of dissociated response' of the alpha cell has been reported in animals after denervation of the pancreas, and insulin-requiring diabetics may develop a selective form of autonomic neuropathy affecting the vagal control of glucagon release.

Adult

Depressed lymphocyte function after bereavement.

During 1975 twenty-six bereaved spouses took part in a detailed prospective investigation of the effects of severe stress on the immune system. T and B cell numbers and function, and hormone concentrations were studied approximately 2 weeks after bereavement and 6 weeks thereafter. The response to phytohaemagglutinin was significantly depressed in the bereaved group on the second occasion, as was the response to concanavalin A at 6 weeks. There was no difference in T and B cell numbers, protein concentrations, the presence of autoantibodies and delayed hypersensitivity, and in cortisol, prolactin, growth hormone, and thyroid hormone assays between the bereaved group and the controls. This is the first time severe psychological stress has been shown to produce a measurable abnormality in immune function which is not obviously caused by hormonal changes.

Adult

Pituitary adenomas and dyspituitarism.

Recent studies of the structure and function of pituitary adenomas reveal that the majority are functional and that the commonest type is a prolactin secreting adenoma. Studies of hypothalamic-pituitary function provide evidence to suggest that the adenoma develops following prolonged hypothalamic stimulation of the pituitary gland, and that the clinical dyspituitarism is due to the hypothalamic-pituitary dysfunction and not to pituitary destruction by the adenoma. Pituitary adenomas may be classified into those due to a basic neuroendocrine dysfunction (prolactin secreting, acromegaly, Cushing's disease) and those arising secondary to end-organ failure (TSH and FSH secreting). The former group have APUD characteristics and may form part of a pluriglandular syndrome of apudomas. The persistence of a basic neuroendocrine dysfunction following the surgical removal of an adenoma explains the frequent recurrence of symptoms in patients and indicates a need for continued surveillance and long-term therapy.

Acromegaly

Effects of triiodothyronine administration in patients with chronic renal failure.

Clinically euthyroid patients with severe, chronic, non-thyroidal illnesses usually have decreased serum total and absolute free T3 concentrations. Since T3 is the metabolically more active of the two thyroid hormones, it has been suggested that these patients may be hypothyroid and thus may benefit from T3 therapy. To test this hypothesis, five patients with chronic renal failure requiring maintenance haemodialysis were treated with 5 microgram T3 eight hourly, increasing at three weekly intervals to 10 microgram eight hourly, 20 microgram eight hourly and finally 30 microgram eight hourly. The mean +/- SD serum T3 level did not change over the 12 week period (1.42 +/- 0.17 vs. 1.41 +/- 0.26 nmoll-1 whilst the mean serum T4 and TSH levels fell from 87.0 +/- 15.2 to 47.5 +/- 18.8 nmoll-1 and 1.9 +/- 0.9 to 1.3 +/- 1.6 mUl-1 respectively. Only the change in T4 levels was significant (P less than 0.005). A significant decrease in mean serum T4 levels was apparent even after the treatment period with 5 microgram T3 eight hourly (87.0 +/- 15.2 vs. 51.2 +/- 15.7; P less than 0.005). The mean fasting serum triglyceride level fell from 1.16 +/- 0.74 to 0.94 +/- 0.74 mmoll-1 (P less than 0.05) and the mean fasting serum cholesterol level fell from 6.06 +/- 1.13 to 4.69 +/- 1.10 mmoll-1 (P less than 0.05). There were no subjective improvements in any of the patients. From the marked changes in serum T4 levels during the administration of T3, it is concluded that, prior to treatment, the patients were biochemically euthyroid and not hypothyroid and thus did not require T3 therapy.

Adult

Control of blood glucose in diabetics using an artificial pancreas.

Studies have been performed using an on-line computer system programmed for blood gucose control of insulin and dextrose infusion (artificial pancreas). The aim of these studies was to test performance of the artificial pancreas and to suggest directions for future optimisation. Blood glucose stabilisation studies of diabetic volunteers were extended throughout the day and included three main meals and light exercise periods. Monitoring of blood glucose profiles of the same diabetics after depot insulin were performed on a separate occasion for comparison. The presence of insulin antibodies did not impair operation of the artificial pancreas. Most of the insulin infused by the artificial pancreas was to initially correct hyperglycaemia with relatively little required to subsequently maintian euglycaemia. The afternoon intra-meal average infusion rate was 0-9 U/hr. It is suggested that correction of fasting hyperglycaemia and maintenance of euglycaemia in diabetics be treated as separate control problems for the artificial pancreas. The overall ability of the artificial pancreas to control blood glucose to a degree not attainable by conventional insulin therapy is confirmed, in this case under conditions which include patient activity.

Adult