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Biomedical subjects

B Hamberger

Publications and source records attributed to B Hamberger.

At least 73 records · Page 4Linked to original sources

Neuropeptide Y-like immunoreactivity in adrenaline cells of adrenal medulla and in tumors and plasma of pheochromocytoma patients.

The occurrence of neuropeptide Y (NPY)-like immunoreactivity (LI) in the adrenal gland of several species as well as in tumor tissue and plasma from pheochromocytoma patients was investigated. NPY-LI was present in chromaffin cells of the adrenaline type in all species investigated except in the pig, as demonstrated by a colocalization of NPY-LI and the adrenaline-synthetizing enzyme phenylethanolamine N-methyltransferase (PNMT). NPY-LI in the adrenaline cells of the cat was clearly separated from the neurotensin-LI in the noradrenaline dopamine-beta-hydroxylase-positive, PNMT-negative cells. NPY-LI seems to co-exist with enkephalin-like material in the chromaffin cells. In addition, NPY-LI was present in nerves both within the adrenal cortex and medulla. The highest levels of NPY-LI were found in mouse and cat, while only a very low amount of NPY-LI was present in the pig adrenal. Characterization of the adrenal NPY-LI by reversed-phase high-performance liquid chromatography revealed that the main peak was similar to porcine NPY. In addition, two minor peaks of NPY-LI were present. High levels of NPY-LI were found in plasma and tumors from the pheochromocytoma patients. During manipulation of the tumors upon surgical removal, there was a marked increase in plasma NPY-LI in parallel with the raise in catecholamines and in blood pressure. At least two forms of NPY-LI were present in plasma and tumor extracts from pheochromocytoma patients with the main peak corresponding to porcine NPY. Since NPY exerts vasoconstrictor effects, it may be postulated that NPY contributes to the adrenal cardiovascular response and to the hypertension seen in pheochromocytoma patients.

Adrenal Gland Neoplasms↗

The influence of abdominal surgical trauma on the exchange of blood-borne amino acids in the human leg.

Associated with surgical trauma is an increased release of gluconeogenic substrates from the periphery. The present study was undertaken to investigate the peripheral exchange of blood and plasma amino acids as well as some other gluconeogenic substrates (lactate and glycerol) in connection with abdominal surgery. Measurements of leg blood flow and femoral arterio-venous substrate differences were made before, during and immediately after elective cholecystectomy. Blood and plasma concentrations of most amino acids except alanine decreased during and immediately after surgery. Simultaneously there was an increased release of several of the amino acids as well as lactate and glycerol from the leg. The total release of plasma amino acids from one leg in the immediate postoperative period was about 2.5 times as high as before surgery. The turnover rates of amino acids as well as the changes in turnover rates were comparable whether the calculations were made from plasma or whole blood concentrations. At the end of surgery there was a high peripheral uptake of 3-hydroxybutyrate concomitant with a low release of amino acids.

Journal Article↗

The role of glucagon, catecholamines and cortisol in counterregulation of insulin-induced hypoglycemia in normal man.

To study the response of glucose counterregulation to insulin-induced hypoglycemia, six normals were given a 4-hour infusion of insulin (2.4 U/h) +/- somatostatin (50 micrograms/h). Supplementary glucagon (1.5 or 3.0 ng/kg/min) was given in additional experiments. In a separate study, glucagon was supplemented for 4 hours as a constant rate infusion (3.25 ng/kg/min) or at rates stepwise increasing from 1.5 to 5.0 ng/kg/min. Insulin decreased blood glucose by 1.5 mmol/l and simultaneous suppression of glucagon resulted in a more pronounced hypoglycemia enhancing the adrenaline and cortisol responses. The hyperglycemic effect of glucagon substitution (3 ng/kg/min) faded out after about 2 hours, whereafter exaggerated adrenaline and cortisol responses to hypoglycemia were seen. A comparison between the effects of steady state hyperglucagonemia and gradually appearing hyperglucagonemia on the counterregulation of hypoglycemia revealed no significant differences in glucose, adrenaline and cortisol responses to insulin. It is concluded that the glycemic effect of glucagon is transient in the hypoglycemic state. When the hepatic responsiveness to this hormone is decreased during hypoglycemia, adrenaline becomes the essential protective factor.

Adult↗

Increase in muscular strength following surgery for primary hyperparathyroidism.

The muscle strength of the quadriceps muscle was measured in a computerized modified Cybex II muscle dynamometer. The method used is easy and has an error of greater than 5%. A marked increase in muscular strength was found after successful surgery for primary hyperparathyroidism (PHPT) with normalization of serum calcium levels. The results support the opinion that all patients with PHPT, with or without muscle weakness, should be recommended an operation if no serious contra-indications exist.

Adult↗

Nutritional status and endocrine response to hemorrhage.

Hyperglycemia-inducing hyperosmolality has recently been proven beneficial in the maintenance of blood volume and extracellular fluid volume during early hemorrhagic hypotension. Fed animals benefitted from better plasma refill compared with starved ones when subjected to equal blood loss. Using lightly sedated fed and 24-30 h starved rats, hormones with relevance to glucose homeostasis were studied during 90 min of hemorrhagic hypotension of 70 mmHg (1 mmHg = 133.32 Pa). Marked differences in the overall hormonal developments were found between the two groups. In fed rats, insulin and glucagon responses were initially attenuated, while somatostatin increased to an early peak level at 30 min, returning to basal at 90 min. In starved rats, somatostatin increased gradually during the 90 min. Adrenaline release was massive in both groups. Corticosterone showed no increase from basal levels in the fed group during hemorrhage, while starved rats increased their basal level fourfold already at 30 min. These data are presented as evidence that changing nutritional status alters hormonal response to hypovolemic stress.

Animals↗

Counterregulation of insulin-induced hypoglycaemia in primary hypothyroidism.

Hypothyroidism has been alleged to modulate insulin action and influence the secretion of growth hormone and catecholamines. We recently investigated the influence of hypothyroidism on glucose counter-regulatory capacity and the hormonal responses to insulin-induced hypoglycaemia in 6 patients with primary hypothyroidism (age 32-52 years, TSH-values 66-200 mU/l). Hypoglycaemia was induced in the hypothyroid state and again when the subjects were euthyroid. After an overnight fast a constant rate infusion of insulin (2.4 U/h) was given for 4 h. Glucose was measured every 15 min and insulin. C-peptide, glucagon, epinephrine, norepinephrine, growth hormone and cortisol every 30 min for 5 h. During insulin infusion somewhat higher concentrations of the hormone were obtained in the hypothyroid state and simultaneously glucose levels were 0.5 mmol/l lower. As expected, basal norepinephrine levels were higher in hypothyroidism. However, no increase in circulating norepinephrine during hypoglycaemia was registered in the two experiments. The responses of counterregulatory hormones showed an enhanced response of cortisol, similar responses of growth hormone and epinephrine while the glucagon response was paradoxically impaired. Our findings suggest that hypothyroidism alters insulin metabolism, and that the glucagon response to hypoglycaemia is impaired in this condition.

Adult↗

Prognostic value of nuclear DNA content in follicular thyroid tumours.

The prognostic value of nuclear DNA content in follicular thyroid tumours was studied in 65 patients. Forty-six (20 with follicular carcinoma and 26 with follicular adenoma) were alive at least 10 years after diagnosis, and 19 had died of follicular thyroid carcinoma 2 months to 13 years after diagnosis. DNA was measured in morphologically identified single tumour cells either on material from fine-needle aspiration biopsy or on histologic sections from the primary tumours. Metastases or locally recurrent tumour were also examined in ten cases. The tumours from the surviving patients had cells with DNA content comparable to that in normal cells, whereas the tumours from the nonsurvivors showed higher DNA values. Primary tumours had essentially the same DNA content as metastases or local recurrence in eight of the ten studied cases. The data suggest that DNA measurement in follicular thyroid tumours offers a valuable addition to standard clinical and microscopic analysis.

Adenocarcinoma↗

Neuropeptide Y and sympathetic vascular control in man.

A parallel increase in systemic plasma levels of neuropeptide Y (NPY)-like immunoreactivity (LI) and noradrenaline (NA) was found during thoracotomy and surgery involving cardiopulmonary bypass in man. Thus, plasma levels of NPY-LI increased from 29 +/- 4 pmol/l before anaesthesia to 59 +/- 10 after thoracotomy and to 87 +/- 8 pmol/l upon cardiopulmonary bypass. The corresponding NA levels increased from 1.3 +/- 0.1 nmol/l before anaesthesia to 3.0 +/- 0.6 and 4.2 +/- 5 nmol/l after thoracotomy and cardiopulmonary bypass, respectively. A significant correlation was found between plasma levels of NPY-LI and NA during the operation but not between NPY-LI and adrenaline. The NPY-LI in human plasma was found to be similar to synthetic porcine NPY on reversed phase high performance liquid chromatography. Human submandibular arteries contained high levels of NPY-LI (24 +/- 3 pmol/g). In in vitro experiments on isolated human submandibular arteries, NPY in low concentrations (1000 pmol/l) was found to potentiate the contractile effects of NA or transmural nerve stimulation and to exert vasoconstrictor activity per se in higher concentrations. The calcium-entry antagonist nifedipine abolished both the NPY-induced contractions and the enhancement of NA-evoked contractions. NPY depressed the nerve stimulation-evoked 3H-NA release from human submandibular arteries via a prejunctional mechanism which was resistant to nifedipine. NPY contracted human mesenteric veins and renal arteries, but not mesenteric arteries. In conclusion, NPY seems to be co-released with NA upon sympathetic activation in man. Furthermore, NPY exerts both pre- and postjunctional effects on sympathetic control of human blood vessels.

Adult↗

Effect of improved glycemic control by continuous subcutaneous insulin infusion on hormonal responses to insulin-induced hypoglycemia in type 1 diabetics.

Glucose counter-regulatory capacity and the hormonal responses to insulin-induced hypoglycemia were studied in eight type 1 diabetics before and after improvement of metabolic control by continuous subcutaneous insulin infusion (CSII). The intensified treatment resulted in a decrease in mean glycosylated hemoglobin from 11.6 +/- 0.5 to 9.3 +/- 0.4% within a mean period of 14 weeks. During a constant rate infusion of insulin (2.4 U/h), steady state levels of glucose appeared in all subjects. The steady state glucose level was identical before and after CSII. The counter-regulatory hormonal responses showed significantly higher epinephrine levels, while glucagon, growth hormone, and cortisol were not influenced. In parallel with the heightened epinephrine response the pulse rate response was significantly enhanced. The restitution of blood glucose after insulin hypoglycemia was not modified. It is concluded that a more vigorous catecholaminergic response to hypoglycemia is achieved after improved metabolic control by CSII.

Adult↗

Cardiovascular responses and plasma catecholamines in old age.

Plasma catecholamines and haemodynamic responses to isometric handgrip, orthostatic body position and dynamic cycle exercise were studied in 10 healthy old men (mean age 71 years) and 10 healthy young men (mean age 26 years). At rest, plasma noradrenaline (NA) was significantly higher in the old age group. During handgrip there were greater increases in heart rate and blood-pressure in the young rather than in the old men, while forearm blood-flow increase was similar in the two age groups, and there was no increase in NA in either groups. In the orthostatic position heart rate increased in the young men only, and forearm blood-flow decreased more in the young than in the old men. NA concentration increased similarly in both age groups. During dynamic exercise the increases in both the heart rate and the blood-pressure, at similar relative submaximal as well as maximal loads, were smaller in the old men. At maximal work NA and adrenaline (A) concentrations were higher in the young men, while at the lowest load, NA concentration was higher in the old men. Similar increases in exercise heart rate, blood-pressure or rate of perceived exertion corresponded to lower increases in NA in the old men. It can be concluded that old men, compared with young men, have a reduced maximal capacity to release NA and A upon provocation. In addition, the sensitivity for catecholamines in the target organ is reduced with age, as suggested by the smaller increases in heart rate and blood-pressure for a given increase in NA during exercise. The higher basal NA level and the higher NA level, during moderate provocation, may suggest a compensatory increase in activity.

Adult↗

Anaemia in primary hyperparathyroidism--fantasy or reality.

Controversy exists as to whether primary hyperparathyroidism is associated with an anaemia. Records corresponding to 215 patients operated on at the Karolinska Hospital between 1972 and 1981 were reviewed. An incidence of 7.4% of anaemia was found, but in only 3% of these cases the anaemia could not be explained by any other known cause. The anaemic group was characteristic in presenting a normochromic and normocytic picture, with iron and serum transferrin values below the normal range. No renal or osseous pathology was observed. In these patients, the anaemia disappeared after the parathyroidectomy, and iron values remained below the normal range. In conclusion, a mild normochromic and normocytic anaemia that disappeared after parathyroid surgery was observed in six patients with PHPT (3%). Its mechanisms are obscure, but data available suggest that parathyroid disease could be of aetiological importance.

Anemia↗

Primary aldosteronism. Clinical management.

We retrospectively reviewed the clinical features, methods of diagnosis and localization, and results of treatment in 105 patients with primary aldosteronism seen between 1969 and 1981. Coincident with the use of computed tomography (CT), 131I-6-beta-iodomethyl norcholesterol scans (NP-59), and postural response studies, the study group was temporally divided into pre-1976 and post-1976 groups, and subdivided into groups with aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) due to bilateral adrenal hyperplasia. Our results indicate that aldosterone postural response studies and CT differentiate and localize APA and IHA reliably. Adrenalectomy is a safe and effective treatment for APA, whereas medical treatment alone is preferable for IHA.

Adenoma↗

Suckling in lactating women stimulates the secretion of insulin and prolactin without concomitant effects on gastrin, growth hormone, calcitonin, vasopressin or catecholamines.

The levels of growth hormone, vasopressin, prolactin, calcitonin, gastrin, insulin, epinephrine, norepinephrine and dopamine were measured in six lactating women during breast feeding. Prolactin levels increased in response to suckling as expected. In addition, insulin levels rose two-fold. No consistent changes were observed in the levels of the other hormones. It is suggested that the suckling related insulin release is either secondary to a reflexly induced activation of the vagal nerves or to the increased circulating levels of prolactin. Furthermore, it is suggested that the insulin release in response to suckling participates in the stimulation of milk production.

Adult↗

Plasma catecholamine and free fatty acid levels during infusion of lipid emulsion in critically ill patients.

The fractional elimination rate of exogenous fat, and fat-mobilizing lipolysis in relation to plasma catecholamine (CA) levels were studied in seven ventilator-treated ICU patients. Blood levels of CA, triglycerides, cholesterol and free fatty acids (FFA) were also analyzed before and during constant infusion of a soybean oil emulsion (Intralipid). Triglyceride concentrations rose significantly during the infusion. FFA levels also increased significantly within 30 min after the infusion was begun, reflecting fatty acids derived from Intralipid triglycerides. Plasma norepinephrine levels showed large interindividual variations and were inversely related to FFA concentrations. No correlation was found between plasma CA levels and the fractional removal rate of fat. These data suggest a deficiency of substrate in these critically ill patients.

Adult↗

Impaired counter regulation of hypoglycemia in a group of insulin-dependent diabetics with recurrent episodes of severe hypoglycemia.

The counterregulatory response to insulin-induced hypoglycemia was investigated in 22 insulin-dependent diabetics (IDD) with recurrent hypoglycemia and in 6 healthy volunteers. Hypoglycemia was induced by a constant rate infusion of insulin (2.4 U/h) up to four hours. Conventional insulin therapy was changed to an i.v. infusion of regular insulin 24 hours prior to the experiment. The presence of diabetic autonomic neuropathy was evaluated by respiratory sinus arrhythmia and Valsalva maneuver. In healthy subjects, blood glucose was decreased to 2.5 mmol, here reaching steady state level and giving rise to marked glucagon and growth hormone (GH) responses. The majority of IDD (group A) reached a slightly lower steady state glucose level and exhibited similar glucagon and GH responses while the epinephrine response was augmented. Six IDD (group B) showed a continuous decrease in blood glucose to 1.2 +/- 0.1 mmol/l at which level the infusion of insulin was discontinued due to neuroglucopenic symptoms. These subjects had no glucagon and epinephrine responses while their GH and cortisol responses were normal. A comparison of the diabetic groups revealed a longer duration of diabetes and a more impaired autonomic nervous function in group B while glycosylated hemoglobin was similar. It is concluded that most IDD have normal hormonal responses (epinephrine, glucagon, GH, cortisol) and normal counterregulartory capacity to hypoglycemia induced by a prolonged infusion of a moderate dose of insulin. Some patients with long-term diabetes and impaired capacity to counteract hypoglycemia exhibit deficient glucagon and epinephrine responses to hypoglycemia.

Adult↗

The possible role of circulating catecholamines in the control of gastric function in health and duodenal ulcer disease.

The relation between gastric acid secretion and plasma concentrations of adrenaline, noradrenaline, dopamine and gastrin was investigated in normal volunteers, adrenalectomized subjects and patients with duodenal ulcer (DU) during digestion and in response to insulin and modified sham feeding (MSF). Basal plasma noradrenaline concentrations were significantly higher in DU patients than in normals whereas basal plasma adrenaline and dopamine concentrations were low in both groups. Basal acid output was similar in the two groups. Insulin markedly increased plasma adrenaline in controls but had no discernible effect in adrenalectomized subjects. Still, there was no difference between acid secretion in the two groups. Insulin, but not MSF, caused a marked increase in plasma catecholamine concentrations in DU patients whereas the acid responses were the same. The significantly increased plasma noradrenaline concentration in DU patients was normalized 6 weeks after highly selective vagotomy but tended to return to the preoperative value 1 year postoperatively. Our results suggest that endogenously released adrenaline might affect gastric function only when present in extremely high plasma concentrations. The pathophysiological role of noradrenaline in DU disease remains obscure.

Catecholamines↗