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Biomedical subjects

F Skrabal

Publications and source records attributed to F Skrabal.

At least 55 records · Page 3Linked to original sources
PubMed1989

[Changes in the catecholamine plasma level 3 months after aortocoronary bypass operation].

Plasma catecholamine levels were obtained during diagnostic heart catheterization from the pulmonary artery and aorta and, similarly, renin levels were determined in the pulmonary artery in 31 patients with coronary heart disease and 18 normal controls. 3 months after aorto-coronary bypass surgery the patients with coronary heart disease underwent repeat heart catheterization and the epinephrine, norepinephrine and renin levels were compared with those obtained before operation. Norepinephrine decreased in the aorta from (means +/- SEM) 475 +/- 57 pg/ml to 360 +/- 38 pg/ml (p less than 0.001) postoperatively (controls 225 +/- 21 pg/ml). Epinephrine decreased from 121 +/- 11 pg/ml to 108 +/- 16 pg/ml (p less than 0.001) postoperatively (controls 84 +/- 9 pg/ml). This shows that postoperative relief from myocardial ischemia is associated with normalization of the preoperatively elevated plasma catecholamine levels).

Adult↗
PubMed1989

Inverse regulation of alpha-2 and beta-2 adrenoceptors in salt-sensitive hypertension: an hypothesis.

A high salt diet leads to up-regulation of alpha-2 adrenoceptors and down-regulation of beta-2 adrenoceptors in normotensive subjects. Although the increase in blood pressure with a high salt diet is not related to the magnitude of the alpha-2 or beta-2 adrenoceptor changes alone, it is related to the increase in the ratio of the receptor changes (operative alpha/beta adrenoceptor ratio). An increase in the operative alpha/beta adrenoceptor ratio with a high salt intake results in vasoconstriction and reduced vasodilatation at resistance vessels, as well as increased renal proximal tubular sodium reabsorption. An influence of heredity on this relationship is supported by four lines of evidence: 1) salt-sensitivity of blood pressure occurs predominantly in subjects with a family history of hypertension; 2) studies in twin children document the influence of genetic variance on salt-sensitivity of blood pressure; 3) subjects with a family history of hypertension have a significantly lower salivary sodium concentration and an altered urinary sodium excretion after salt loading compared to subjects with no such history; 4) salt-sensitivity of blood pressure may be associated with specific genetic markers. On the basis of these observations, we propose the hypothesis that enhanced inverse alpha-beta-adrenoceptor regulation in response to a high salt intake may be responsible for salt sensitivity in the normal population, and may contribute to the development of essential hypertension in susceptible individuals. This alteration is likely to be genetically mediated.

Down-Regulation↗
PubMed1988

Genetic influences on the response to dietary salt reduction, acute salt loading, or salt depletion in humans.

The effect of heredity on blood pressure is established. However, not all genetically predisposed individuals develop an elevated blood pressure. Thus, an environmental factor may also be required for expression of this genetic predisposition. To elucidate this effect further, as well as to examine the relationship between inherited factors and the influence of salt intake, we conducted acute and chronic investigations in normal subjects. We present evidence that renal function, the renin-angiotensin-aldosterone system, and sympathetic nervous system are all influenced by genetic variance. We found that the blood pressure response to both acute changes in volume and changes in salt intake is normally distributed, supporting the notion of salt sensitivity and resistance of blood pressure. We identified phenotypes of haptoglobin as possibly useful indicators of salt sensitivity and resistance. We documented a parent-offspring resemblance in blood pressure and also a maternal-offspring resemblance in the change in blood pressure with salt reduction. We present evidence that suggests that salt-sensitive persons exhibit differences in renin-aldosterone relationships and natriuretic responses consistent with volume expansion compared to salt-resistant individuals. Finally, we identified a potential role for altered adrenoreceptors in the development of salt sensitivity. Our observations speak to the inherited nature of salt sensitivity and resistance of blood pressure. They may have mechanistic implications as well.

Diet, Sodium-Restricted↗
PubMed1987

Ectopic corticotrophin-releasing-factor and growth hormone releasing factor secretion: diagnosis using human pituitary cell culture.

Cell culture of human pituitary tissue has been used to diagnose a patient with Cushing's syndrome due to ectopic secretion of corticotrophin-releasing factor (CRF; case 1) and a case of acromegaly associated with ectopic secretion of a growth-hormone releasing factor (GRF; case 2). In both patients a pituitary tumour was not detected. Case 1 had a small cell carcinoma and symptoms of the ectopic ACTH syndrome, but in culture the carcinoma failed to secrete detectable ACTH. However, the culture medium used to maintain this carcinoma in vitro was found to contain a substance which stimulated ACTH secretion by human pituitary corticotrophs in cell culture. Radioimmunoassays and HPLC indicated that this substance had similar elution characteristics to human CRF and cross-reacted with antiserum to ovine CRF. Case 2 was found to have a lung tumour, the removal of which led to regression of her acromegalic symptoms. In culture, this tumour did not secrete GH, but did secrete a GRF. We conclude that the Cushing's syndrome and acromegaly, in cases 1 and 2, respectively, were due to ectopic secretion of CRF and GRF leading to hyperstimulation of the pituitary gland.

Acromegaly↗
PubMed1987

Adrenergic receptors and sodium reabsorption in normotensive subjects as related to salt sensitivity.

We have studied proximal tubular sodium reabsorption as measured by lithium clearance, alpha-2 and beta-2 adrenergic receptors on circulating platelets and lymphocytes, respectively, and urinary aldosterone after variations of sodium intake in 24 normotensive volunteers. Fractional lithium clearance was 14.8% +/- 2.64 under a high salt diet of 200 mmol per day. After a low salt diet of 50 mmol/d for two weeks fractional lithium clearance did not change significantly (13.3% +/- 3.35). There were no correlations between alpha-2 adrenergic receptors, beta-2 adrenergic receptors or the alpha-2/beta-2 ratio and fractional lithium clearance, irrespective of the high or low salt diet. In contrast, a significant correlation was found between urinary aldosterone excretion and alpha-2 receptor densities under low salt diet (r = -0.55, n = 17, p less than 0.02). There were no correlations between beta-2 adrenoceptor density, alpha-2/beta-2 ratio and urinary aldosterone during high or low salt diet. Whereas our results are inconclusive about the value of lithium clearance determinations as a measure of proximal tubular sodium reabsorption during variations of sodium intake, we conclude, that alpha-adrenoceptor density, as measured on circulating blood cells, may possibly be representative for alpha-adrenergic equipment of the kidney. The inverse correlation between urinary aldosterone excretion in subjects equilibrated on a low salt diet of 50 mmol/d and alpha-2 adrenoceptor densities could be interpreted as an indirect evidence, that those subjects with a high alpha-2 adrenoceptor equipment show a high proximal tubular sodium reabsorption and thus can afford a low rate of aldosterone mediated distal tubular sodium reabsorption to maintain sodium balance. Our results are thus in accord with our previous hypothesis, that different receptor equipment of individual subjects may cause marked differences in sodium handling by the kidney. These differences may be responsible, at least in part, for the degree of salt sensitivity in individual subjects.

Absorption↗
PubMed1987

Macroprolactinomas and functionless pituitary tumours. Immunostaining and effect of dopamine agonist therapy.

In 32 patients with macroprolactinomas or functionless pituitary macroadenomas biochemical and clinical data were correlated with PRL immunocytochemistry. Serum PRL levels revealed a positive correlation with tumour PRL content. Hyperprolactinaemia of 3000 mU/l or more was found only in patients with PRL-positive tumours. In 15 patients with borderline hyperprolactinaemia (below 3000 mU/l), 7 PRL-positive and 8 PRL-negative macroadenomas were found, and in 9 normoprolactinaemic patients 4 PRL-positive and 5 PRL-negative macroadenomas. Patients with PRL-immunostainable tumours had significantly higher median basal serum PRL (P less than or equal to 0.05) than patients with PRL-negative tumours. PRL stimulation after TRH, basal and GnRH-stimulated FSH and LH did not show significant differences between the two groups. A discriminant analysis using 6 biochemical variables was attempted to differentiate between PRL-negative and -positive tumours, which would be helpful in patients with borderline hyperprolactinaemia. Dopamine agonist therapy led to suppression of serum PRL with few exceptions in patients with PRL-positive and -negative tumours, whereas shrinkage was only observed in PRL-immunostainable tumours with high serum PRL levels (over 18,000 mU/l). All patients with PRL-negative tumours showed no change or even growth of the tumour despite dopamine agonist therapy. Our observations indicate that a pituitary macroadenoma associated with serum PRL of more than 3000 mU/l is most probably a prolactinoma (tumour immunostainable for PRL). Dopamine agonist therapy is effective in PRL suppression and tumour shrinkage in most of these patients. Macroadenomas without hormone hypersecretion or with borderline hyperprolactinaemia below 3000 mU/l may or may not contain PRL-immunostainable cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1986

Lactose absorption, milk consumption, and fasting blood glucose concentrations in women with idiopathic osteoporosis.

Lactose tolerance tests were performed in 33 women with osteoporosis and 33 control women matched for age. A questionnaire was used to elicit any history of milk intolerance and the subjects' daily intake of calcium derived from milk and dairy products. Eleven patients and four controls gave a history of milk intolerance (p less than 0.01); 13 patients had lactose malabsorption compared with four controls (p less than 0.01). The daily intake of calcium derived from milk was significantly lower in patients (125 (SEM 20) mg v 252 (43) mg; p less than 0.05). Curves of blood glucose concentrations during the lactose tolerance test in subjects with lactose malabsorption were significantly flatter in patients than controls (p less than 0.05). The fasting blood glucose concentration was higher (5.44 (0.17) mmol/l (98 (3) mg/100 ml) in the patients than the controls (4.88 (0.11) mmol/l (88 (2) mg/100 ml); p less than 0.05), although body weight was significantly lower (61.6 (2.2) kg v 66.3 (1.6) kg; p less than 0.05). Absorption of lactose is significantly impaired in women with "idiopathic" osteoporosis; this combined with low consumption of milk and a subclinical disorder of glucose metabolism may be a major factor in the development of idiopathic osteoporosis in women.

Adult↗
PubMed1986

Up-regulation of alpha 2 adrenoceptors and down-regulation of beta 2 adrenoceptors by high-salt diet in normotensive men: enhanced up-regulation of operative (alpha 2:beta 2) adrenoceptor ratio predicts salt sensitivity.

In 24 normotensive male volunteers (age 20-25 years) reduction of sodium intake from 200 to 50 mmol/day over 2 weeks resulted in a 14% fall of alpha 2-adrenoceptors of platelets from 209.5 to 179.4 fmol/mg (P less than 0.01) and in a 16% rise of beta 2-adrenoceptors of lymphocytes from 13.3 to 16.2 fmol/mg (P less than 0.05) which was reversible by 2 weeks of high sodium intake. In contrast to the comparatively minor changes of alpha 2- and beta 2-adrenoceptor density, the functionally probably more relevant 'operative (alpha 2:beta 2) adrenoceptor ratio' decreased by 53% from 22.9 to 14.9 (P less than 0.01) during the low-salt diet. Although neither the individual changes of alpha 2- and of beta 2-adrenoceptor densities correlated with individual blood pressure changes induced by variations in sodium intake, there was a highly significant positive correlation (r = 0.55, n = 33; P less than 0.01) between the rises of the 'operative adrenoceptor ratio' and the rises of blood pressure induced by high salt intake. We conclude that the 'operative adrenoceptor ratio', although only determined on alpha 2- and beta 2- and not on alpha 1- and beta 1-adrenoceptors, and only on circulating blood cells, may be representative for sympathetic resistance vessel tone, at least as a function of variations of salt intake. Enhanced up-regulation of the 'operative adrenoceptor ratio' in the salt-sensitive part of the population may be one important early step in the development of essential hypertension.

Adult↗
PubMed1985

[Hereditary salt sensitivity as a cause of essential hypertension: studies of membrane transport and intracellular electrolytes].

Based on oscillatory long-term blood pressure recordings and on biochemical findings in 62 normotensive and 54 untreated hypertensive subjects, who were investigated during their usual high sodium diet and after moderate salt restriction, we have developed a concept for the pathogenesis of essential hypertension, which differs from current concept proposed by others: We demonstrated that normotensive subjects with a positive family history of hypertension respond to sodium restriction from 200 to 50 mmol/day over 2 weeks with a minute fall of mean blood pressure of 2.9 +/- 0.7 mmHg (+/- SEM), whereas in subjects with a negative family history of hypertension blood pressure remained unchanged (-0.93 +/- 0.67 mmHg). This difference was only revealed by computing the "basal blood pressure average" from 240 heart beats, but not by conventional sphygmomanometric blood pressure measurements. Normotensives with heredity of hypertension or "salt sensitive" normotensive subjects were not different from subjects with a negative family history in the sodium pump, Na-K-cotransport or intracellular sodium and potassium of erythrocytes. In contrast, the former group had an increased sensitivity to infused noradrenaline, which might be responsible for enhanced tubular sodium reabsorption in subjects with a positive family history of hypertension (or "salt sensitive" subjects). We only found an increased K-permeability of red cells in established hypertension, which was compensated for by a an increased activity of the sodium pump. These cell membrane defects were more pronounced in more severe hypertension. In the course of essential hypertension a cell membrane defect may develop as a consequence rather than a cause of the disease.

Adult↗
PubMed1985

Multiple intracranial metastases from a prolactin secreting pituitary tumour.

A 28 year old man presented with partial hypopituitarism and signs of a pituitary tumour. A chromophobe adenoma was partially removed by right frontal craniotomy. Seven years later complete hypopituitarism and hyperprolactinaemia were documented, at which time there was no evidence of tumour recurrence of CT scan. The patient was treated with bromocriptine but the pituitary tumour redeveloped a year later. Nine years after the original operation the first metastasis was demonstrated together with very high prolactin levels. The intracranial metastasis, and the pituitary tumour were removed at a second craniotomy following which the prolactin concentration fell. Further metastases developed subsequently and the patient died 12 years after the initial diagnosis. At autopsy multiple metastases were found in the brain, tumour cells were present in the subarachnoid space and in cerebral veins. The pituitary tumour and secondaries were shown by immunocytochemistry to contain prolactin but not ACTH or growth hormone. This appears to be the third well documented case of a metastasizing, prolactin secreting pituitary tumour.

Adenoma, Chromophobe↗
PubMed1985

Salt sensitivity in normotensives with family history of hypertension: studies of membrane transport, intracellular electrolytes and alpha 2-adrenergic receptors.

Using long-term automatic blood pressure recording it has previously been shown that subjects with family history of hypertension show a minute fall of blood pressure during sodium restriction, which is reversible by high sodium intake. Thus normotensives with hypertensive antecedents as a group are salt-sensitive, whereas normotensives without heredity of hypertension as a group are salt-resistant. The present study compares intracellular sodium, potassium and calcium, sodium pump activity, NaK-cotransport of red blood cells and density and affinity of alpha 2-adrenergic receptors of platelets in normotensive subjects classified according to family history of hypertension and according to 'salt sensitivity' and 'salt resistance'. Neither the family history of hypertension nor salt sensitivity correlated with intracellular sodium, potassium, calcium, Na-pump activity and NaK-cotransport. Alpha 2-adrenergic density was higher in salt-sensitive than in salt-resistant subjects (P < 0.05) but similar in subjects with a positive and negative family history of hypertension. However, alpha 2-adrenergic receptor density decreased significantly during 2 weeks of moderate salt restriction from 169.6 +/- 34.2 to 142.6 +/- 30.8 (P < 0.01, paired t-test), which may explain the decreased pressor response to infused noradrenaline observed in a previous study during moderate salt restriction. It is concluded that in humans there is no association of genetic predisposition of hypertension or of salt sensitivity to an alteration of sodium pump activity, NaK-cotransport, intracellular sodium and calcium. Alpha 2-receptor density of platelets deserves further study as a possible predictor of salt sensitivity in normotensives.

Adult↗
PubMed1985

Raised sodium pump activity and a circulating sodium transport inhibitor demonstrated on red blood cells of patients with untreated essential hypertension: correlation of pump activity with potassium permeability.

We have studied sodium potassium ATPase activity, the effect of endogenous plasma on sodium pump activity, potassium permeability and intracellular sodium and potassium concentrations in normotensive subjects without (n = 36) and with (n = 33) a positive family history of hypertension, and in patients with untreated essential hypertension (n = 52). Sodium pump activity was studied as ouabain sensitive uptake of rubidium 86 in washed red blood cells, incubated in an artificial medium closely resembling the anorganic constituents of plasma. Any influence of endogenous plasma on sodium pump activity was investigated by re-incubating the washed red blood cells in their own plasma and comparing ouabain sensitive rubidium uptake in the two media. To correct for any possible differences in external potassium concentration, a function for the relation between extracellular potassium concentration and absolute transport rates was derived experimentally. From this, actual transport rates in plasma were corrected by computer to an extracellular potassium concentration of 4.0 mmol/l. Sodium pump activity, concentration of circulating sodium transport inhibitor, potassium permeability and intracellular electrolytes were not statistically different in subjects with and without a positive family history of hypertension. Hypertensives had significantly raised sodium pump activity in artificial medium, but not when red cells were re-incubated in their own plasma. Thus, endogenous plasma inhibited the sodium pump by between 12% and 15%. Hypertensives also had a significantly raised potassium permeability. Potassium permeability and sodium pump activity were correlated significantly. Intracellular sodium concentrations were similar in normotensives and hypertensives, but the later showed a significantly lower intracellular potassium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Salt sensitivity in normotensives with and salt resistance in normotensives without heredity of hypertension.

We have studied blood pressure responses to moderate sodium restriction from 200 to 50 mmol/day over 2 weeks in 62 normotensive subjects with and without a family history of hypertension by continuous automatic blood pressure recording. Based on the average of the blood pressure of 1 hour continuous monitoring under basal conditions, we have been able to demonstrate a significant fall of blood pressure in 28 young subjects with a heredity of hypertension after moderate sodium restriction from 200 to 50 mmol over 2 weeks (fall in systolic blood pressure 5.4 +/- 1.1, diastolic 2.5 +/- 0.8, mean blood pressure 2.9 +/- 0.7 mmHg, mean +/- SEM), whereas blood pressure remained unchanged in a group of 34 subjects without heredity of hypertension after moderate sodium restriction (change in systolic blood pressure -1.0 +/- 0.6, diastolic blood pressure -0.6 +/- 0.7 and mean blood pressure -0.93 +/- 0.67 mmHg). 29 of the subjects were studied a third time 2 weeks after having returned to their usual high sodium diet and in those in whom a blood pressure fall was observed during sodium restriction it returned to pre-intervention values. This demonstrates that normotensives with a heredity of hypertension are salt sensitive and adds further evidence that a high sodium intake may be of critical importance for the initiation of essential hypertension.

Adult↗
PubMed1984

Low-sodium diet versus low-sodium/high-potassium diet for treatment of hypertension.

In 21 patients with essential hypertension the effects of moderate sodium restriction from the usual 200 mmol Na/day to 80 mmol/day over 4 weeks were compared with the effects of a combined low-sodium/high-potassium intake (80 mmol Na/120 mmol K) which was also given over 4 weeks in an open crossover trial. Systolic blood pressure in nine untreated patients with essential hypertension decreased significantly by between 5 and 7 mm Hg during moderate sodium restriction; no further decrease of blood pressure occurred during the combined low-sodium/high-potassium diet. In 12 treated patients with essential hypertension moderate sodium restriction or the combined low-sodium/high-potassium diet enabled a marked reduction of anti-hypertensive therapy in eight patients without impairment of blood pressure control (beta-blockers by an average of 32%, saluretics by an average of 27% and vasodilators by an average of 24%). Here there were also no substantial differences between low-sodium intake and the combined low-sodium/high-potassium intake. It is concluded that sodium restriction to 80 mmol/day is effective in lowering systolic blood pressure but that a combined low-sodium/high-potassium diet does not further improve blood pressure control if the usual potassium intake is at least 80 mmol/day. Considerable reduction of anti-hypertensive therapy may be achieved by practical moderate sodium restriction.

Adult↗
PubMed1984

Inherited salt sensitivity in normotensive humans as a cause of essential hypertension: a new concept.

The following concept of the pathogenesis of essential hypertension is proposed: there may be a continuous spectrum of noradrenergic sensitivity in normal subjects which is not only inherited but also modified later by different levels of psychological stress or by different types of behavior. The higher the noradrenergic sensitivity in a given subject, the greater the salt sensitivity and the greater the likelihood that hypertension will develop in later life if the usual high sodium-low potassium diet is consumed. Noradrenergic hypersensitivity may be linked to salt sensitivity in that it causes enhanced proximal tubular sodium reabsorption which is compensated for by pressure natriuresis. Enhanced pressure natriuresis requires persistently elevated blood pressure which leads to hypertension if maintained for many years. The phenomenon of salt sensitivity does not become apparent with a sodium intake of less than 50 mmol/day. Although enhanced noradrenergic sensitivity also persists with this low-sodium intake, salt-sensitive subjects are able to compensate for the enhanced rate of proximal tubular sodium reabsorption by reabsorbing less sodium at the distal tubules as compared with that reabsorbed by salt-resistant subjects. Enhanced noradrenergic sensitivity and enhanced proximal tubular sodium reabsorption, however, cannot be compensated for by fine-tuning aldosterone secretion while on the usual high sodium diet containing greater than 100 mmol/day. Under these conditions aldosterone secretion is already suppressed to its basal rate and cannot be suppressed more in salt-sensitive than in salt-resistant subjects. Therefore with the usual high sodium diet the enhanced rate of proximal tubular sodium reabsorption in salt-sensitive subjects is compensated for by enhanced pressure natriuresis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗