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Biomedical subjects

M Frölich

Publications and source records attributed to M Frölich.

At least 181 records · Page 10Linked to original sources

Direct and indirect measurement of urinary kallikrein excretion in patients with essential hypertension and normotensives: relation to age and plasma renin and aldosterone levels.

The relevance of age and activity of the renin-angiotensin-aldosterone system to the excretion of urinary kallikrein (Ukal) was studied in twenty-five patients with essential hypertension and forty normotensive controls. The age range for both study groups was 20-60 years. Ukal was measured by radioimmunoassay and by an amidolytic assay. Results of both assays correlated closely (r = 0.93, n = 65, P less than 0.001). For all hypertensives Ukal excretion was not significantly different from that of controls. However, older hypertensives (greater than 40 years, n = 13) had a significantly lower Ukal excretion than normotensives of the same age (n = 20) (radioimmunoassay 67.2 (SEM 7.2) v. 105.1 (SEM 8.4) micrograms (24 h)-1; and amidolytic method 0.84 (SEM 0.10) v. 1.13 (SEM 0.08) U (24 h)-1). No correlation was found between Ukal excretion and plasma renin or aldosterone. In fact, the aldosterone level was highest in older hypertensives. In conclusion, the lower Ukal excretion in hypertensives over 40 is likely to be secondary to the long-standing high blood pressure. Under basal conditions, Ukal excretion seems little influenced by the activity of the renin-angiotensin-aldosterone system.

Adult↗

Radioiodine in the treatment of hereditary medullary carcinoma of the thyroid.

The effect of 131I therapy as an adjunct to surgery in the management of patients with hereditary medullary carcinoma of the thyroid (MCT) was studied in 20 patients from 3 kindreds. Plasma calcitonin levels were measured before and after a dose of 131I sufficient to ablate postoperative thyroid remnants. In patients with residual biochemical MCT no significant reduction of the calcitonin levels was found after administration of radioiodine. In patients with normal postoperative calcitonin levels no (biochemical) recurrence developed 3 months to 2 yr subsequent to radioiodine therapy. It is concluded that 131I therapy as an adjunct to surgery is not indicated in the management of patients with residual hereditary MCT, although 131I may be of value in the prevention of tumor recurrence in patients with normal postoperative calcitonin values.

Adolescent↗

The influence of bromocriptine and transsphenoidal surgery on urinary androgen metabolite excretion in acromegaly.

The urinary excretion of the androgen metabolites aetiocholanolone (E) and androsterone (A) as well as DHEA, 11-hydroxy-androsterone and the cortisol metabolites 11-oxo-aetiocholanolone and 11-hydroxyaetiocholanolone in normoprolactinaemic and hyperprolactinaemic male and female acromegalics was studied and compared with that of appropriate control groups. In addition several plasma hormones were also measured. The growth hormone level in the patient group varied from 10-550 mU/l. The excretion of both 11-hydroxy-androsterone and DHEA was normal. The excretion of androsterone had decreased, while aetiocholanolone and cortisol metabolite excretion had increased. The ratio between aetiocholanolone and androsterone (E/A) excretion was significantly increased in all patient groups, but no correlation was found between the growth hormone level and the E/A ratio. Treatment with bromocriptine caused a decrease in the E/A ratio in patients with decreased growth hormone levels, but not in patients in whom the growth hormone level remained unchanged. After selective transsphenoidal removal of the pituitary adenoma the E/A ratio decreased significantly. The increased E/A ratio in untreated patients could not be attributed to eventual changes in plasma levels of cortisol, thyroxine, prolactin, testosterone or oestrogens. We therefore suggest that growth hormone is involved in androgen metabolism in acromegaly.

Acromegaly↗

Diurnal changes in serum triglycerides as related to changes in lipolytic enzymes, (apo) lipoproteins and hormones in normal subjects on a carbohydrate-rich diet.

Normal subjects in steady state on a carbohydrate-rich diet (three equivalent meals a day at 9.00, 13.00 and 17.00 h), show a wave-like serum triglyceride (TG) pattern with a peak at 14.00 h. Post-heparin lipoprotein lipase (LPL) activity increased from a mean value of 49 mU/ml +/- 13 (SD) in the fasting state to 127 mU/ml +/- 18 in the fed state (P less than 0.005). This was due to an increase in adipose tissue LPL activity which, at 16.30 and 21.30 h, was significantly higher than basal levels (128.3 +/- 81.5 and 87.7 +/- 23.2 v. 43.3 +/- 9.3 mU/g, P less than 0.05 and P less than 0.01, respectively). Skeletal muscle LPL activity was low (5.8 mU/g +/- 2.3, mean +/- SD) and showed no diurnal change. The observed changes in TG-hydrolysing capacity in the course of the day might explain the TG-pattern. High density lipoprotein (HDL) subfractions HDL2 and HDL3 were separated by density gradient ultracentrifugation and had mean hydrated densities of 1.088 and 1.135 g/ml, respectively. While HDL2 showed no diurnal change, HDL3-cholesterol and-phospholipid significantly increased during the day (P less than 0.005 and P less than 0.001 respectively), reaching their highest levels in the evening. Since te rise in HDL3-lipids follows the fall in serum TG, this provides further indication that the metabolism of these fractions in mutually related.

Adipose Tissue↗

Propranolol improves the impaired TSH response to TRH in patients with autonomously functioning euthyroid multinodular goitre.

Ten patients with autonomously functioning euthyroid multinodular goitre received propranolol (Inderal Retard 160 mg daily) for 4 weeks in order to investigate whether normalization of the TRH test or an increased TSH response to TRH could be obtained by decreasing serum T3 levels. Serum T3 decreased significantly after 2 and 4 weeks of propranolol administration. Serum T4 increased during this period, although the change was only significant after 4 weeks of propranolol. T3 resin uptake did not change. The TSH response to TRH increased significantly during the administration of propranolol. Mean delta TSH basally was 1.0, range 0-3.9 mU/l, and mean delta TSH after 4 weeks of propranolol was 2.4, range 0-9.3 mU/l. A strong correlation was found between the increase in delta TSH and the decrease in serum T3 after 4 weeks of propranolol. After withdrawal, delta TSH and T3 returned to premedication levels. Our data suggest that T3 is an important factor in the impairment of the TSH response to TRH in our patients. Normalization of the TRH test was, however, not obtained. These findings support the concept of subclinical hyperthyroidism in 'euthyroid' multinodular goitre with autonomous function.

Adult↗

Primary hypothyroidism as a complication after treatment of tumours of the head and neck.

In 100 successive patients treated for tumour in the head and neck region, the function of the thyroid gland was evaluated during follow-up by determination of the serum levels of thyroid stimulating hormone and thyroxine. Radiation therapy alone did not lead to hypothyroidism, 4 patients had no dysfunction after laryngectomy for recurrent tumour after irradiation. Ten of 17 (59%) patients treated with irradiation and surgery including hemithyroidectomy and with a follow-up period of more than one year developed functional disturbance; in the absence of hemithyroidectomy one of 10. In patients who underwent hemithyroidectomy and developed hypothyroidism, the interval between surgery and postoperative irradiation was shorter than in those who did not develop functional disturbance (31 versus 49 days).

Adult↗

A molecular mechanism of regulation for granulocyte macrophage colony stimulating factor from T lymphocytes.

We have partially purified a mitogenic factor, termed colony stimulating factor, which is secreted from a human T lymphocytic cell line, and which stimulates in vitro formation of colonies of macrophages and granulocytes by human bone marrow cells. Colony stimulating factor (CSF) produced by cells grown in serum supplemented media has a molecular weight of 60,000. It easily dissociates into a low (20,000) and a high (40,000) molecular weight component. The low molecular weight component, F I, initiates colony formation by a subset of the marrow cells. F II, the high molecular weight component, is inactive by itself, but reconstitution of F I with F II causes a dramatic increase in the number of target cells that form colonies. In serum-free media the T-cell line secretes only F I, which can be activated by F II. F II is only present when serum has been added to the medium, yet it is not present in the serum. Therefore, either the lymphocytes modify a component of the serum or they are stimulated to secrete F II by the serum. The molecular properties of this CSF suggest a possible mechanism of regulation of similar factors in that dissociation and reassociation may be physiologically important in determining which cell population is activated in hematopoiesis.

Blood↗

Diurnal levels of lipids, glucose and insulin in type IV hyperlipidemic patients on high carbohydrate and high fat diet: comparison with normals.

Diurnal levels of serum triglyceride (TG), cholesterol, free fatty acids (FFA), glucose and insulin were measured in three type IV hyperlipidemic patients on a fixed solid 65% carbohydrate and a 65% fat diet when in steady state conditions in a metabolic unit. The carbohydrate-rich food was divided into either three or eight equivalent portions, differently spaced over the day and night. The fat-rich food was given in three equivalent portions only. The diurnal TG profiles on these diets showed the same characteristics as those found in normals, but increments and mean levels were considerably higher. On the carbohydrate-rich diet, mean TG levels decreased during the study. This was not seen either on the fat-rich diet or in normals. In contrast to our findings in normals, chylomicrons formed the major contribution to the serum TG pattern. FFA levels were markedly higher on the high-fat than on the carbohydrate-rich diet, but not different from those in normals. Postprandial glucose responses did not differ significantly between the diets. Insulin responses were markedly higher on the carbohydrate-rich than on the fat-rich food. Glucose levels did not differ from those in normals. Insulin levels were significantly higher in the patients. Cholesterol showed minimal fluctuations, parallel to the TG pattern, which could be attributed to chylomicron cholesterol.

Adult↗

Effects of ethinyloestradiol on plasma levels of pituitary gonadotrophins, testicular steroids and sex hormone binding globulin in normal men.

Daily measurements of plasma FSH, LH, prolactin, testosterone, 17 beta-oestradiol and sex hormone binding globulin (SHBG) activity were made in eight healthy, normal men during treatment with oral ethinyloestradiol (EE2) in a dose of 30 micrograms/day for 5 days following a 5-day control period. No significant changes in plasma levels of FSH and prolactin during oestrogen treatment occurred. In contrast, plasma concentrations of both LH and testosterone showed a biphasic pattern. Following an initial suppression during the first 3 days of oestrogen treatment both LH and testosterone increased again to baseline values despite continuation of oestrogen administration. The secondary rise of both hormones was associated with (and probably resulted from) a nearly 100% increase in the plasma concentration of SHBG binding activity, and hence reduction of free testosterone index (FTI). Unlike testosterone, plasma 17 beta-oestradiol during EE2 administration did not show a biphasic pattern, but a progressive decline that was positively correlated with the fall in FTI. The rapidity of onset and magnitude of the observed rise in SHBG levels emphasizes the need for measurement of this binding protein (or the free testosterone fraction) in studies on feedback regulation of gonadotrophins employing exogenous EE2 in human males. The observed increase of SHBG to supraphysiological values suggests that currently employed EE2 doses in such studies may be less 'physiologic' than is often assumed.

Adult↗

The influence of bromocriptine on serum levels of growth hormone and other pituitary hormones and its metabolic effects in active acromegaly.

The effect of treatment with bromocriptine for 12--18 months on serum GH and metabolic responses was studied in sixteen patients with active acromegaly. Of this group ten patients showing a sustained GH reduction of more than 50% during an 8 h bromocriptine test, proved to be responsive to long-term therapy. In the responding patients GH levels decreased to 38% of the pretreatment level after 12 months of therapy. A dose higher than 10 mg did not produce a significantly greater effect. Prolactin and LH levels decreased in all patients, FSH levels showed a significant rise. Testosterone levels in the male patients increased significantly, indicating that the state of hypogonadism can at least be partially reversed. The GH levels became normal in only one patient. We conclude that the role of bromocriptine in acromagaly is limited and selective pituitary operation and/or irradiation is preferred as definitive treatment in most patients.

Acromegaly↗

Influence of meal frequency on diurnal lipid, glucose and insulin levels in normal subjects on a high fat diet; comparison with data obtained on a high carbohydrate diet.

Diurnal levels of serum triglyceride (TG) were measured in six normal persons consuming a fixed solid 65% fat diet under steady state conditions in a metabolic unit. The food was divided into either three or eight similar portions, differently spaced over the day and night. The diurnal TG-profiles on this diet were practically identical to those found under comparable conditions on a 65% carbohydrate diet [1]. Mean diurnal TG values did not significantly differ with varying meal frequency. Free fatty acid levels, however, were significantly higher on a high fat diet. Post-prandial glucose and insulin reponses did not significantly differ whether a high fat diet or a high carbohydrate diet was consumed. We conclude that the composition of the diet is of little importance in determining diurnal TG patterns when the diet consists of normal food stuffs, but that these patterns are dependent on meal frequency and distribution.

Blood Glucose↗

Sex hormone binding globulin: binding capacity and studies on the binding of cyproterone acetate and other steroids.

Sex hormone binding globulin in blood is quantitated by ammonium sulphate precipitation technique with two radioactive ligands, [3H]testosterone and [3H5dihydrotestosterone. Plasma levels in normal men, normal women, women taking oral contraceptives containing oestrogens, and pregnant women are presented, measured with both ligands. Binding experiments with these ligands and several competing steroids show marked differences in displacement ability. For cyproterone acetate 100-500 ng per tube is required to obtain even a slight displacement of the radioactive ligands.

Contraceptives, Oral, Hormonal↗