Angiotensin-converting enzyme inhibition as a therapeutic principle in Bartter's syndrome.

The effect of captopril has been investigated in four patients with Bartter's syndrome treated for 12 weeks. Baseline biochemistry showed normal serum aldosterone (mean 347 pmol.l-1) and a mean serum renin of 217 mU-l-1, and a considerable increase in serum renin during captopril treatment. Serum aldosterone decreased gradually during the study period to about half its initial value. The patients presented with a mean serum potassium of 2.5 mmol.l-1, which rose to 3.4 mmol.l-1 on captopril. Lymphocytes showed a substantial captopril-induced increase in intracellular sodium (from 15 to 22.5 mmol.l-1 on average), but no change in the potassium content. Captopril was well-tolerated. It may be an alternative to potassium-sparing diuretics for maintaining normal serum potassium levels in patients with Bartter's syndrome.

Lymphocytic sodium and potassium pump function in Bartter's syndrome.

Bartter's syndrome is characterized by chronic hypokalaemia, activation of the renin-angiotensin system and normal blood pressure. To investigate whether a generalized disturbance of sodium-potassium pump function might be of pathogenetic importance, lymphocytic sodium-potassium homeostasis was examined in 5 patients suffering from Bartter's syndrome. Two of the patients were treated with potassium chloride supplementation, the others were without medical treatment when studied. All were severely hypokalemic (serum potassium 2.8 +/- 0.24 mmol/l, mean +/- SEM). Lymphocyte sodium and potassium concentration (14.4 +/- 0.37 and 94.4 +/- 7.7 mmol/l, respectively), ouabain sensitive 22Na-efflux rate constant (2.68 +/- 0.25 h), and absolute ouabain sensitive efflux rate (38.16 +/- 4.2 mmol l-1 h) did not differ from matched controls. Ouabain binding capacity was 126 900 +/- 23 500 sites/cell in patients vs 50 400 +/- 17 900 in controls (p less than 0.05). In conclusion, patients with Bartter's syndrome may have an intrinsic abnormal pump function, characterized by an increased pump density and a low cation turn-over rate per pump unit.

Volume, sodium content and sodium efflux of human mononucleated cells: characteristics and methodological problems.

New methods for determining the volume and sodium content of human mononucleated cells are presented and the kinetics of sodium efflux are characterized. Sodium efflux obeyed first-order kinetics with a half-life of about 9 min. The ouabain-sensitive sodium pump is responsible for about 60% of the total turnover of this cation. Reliable measurement of cell volume and sodium content requires pre-incubation at physiological conditions. Determination of sodium efflux should be based on the initial (less than 15 min) cellular delay of 22Na-activity in preloaded cells. In normal subjects (n = 34), mean cell volume was 635 +/- 138 nl/10(6) cells and sodium content averaged 14.6 +/- 2.8 mmol/l cell. Total and ouabain-sensitive efflux rate constants were 4.56 +/- 0.66 h-1 and 2.70 +/- 0.47 h-1. Corresponding absolute sodium efflux averaged 65.1 +/- 14.8 and 38.9 +/- 9.6 mmol/l/h, respectively.

Cell membrane handling of sodium in lymphocytes during salt restriction in normotensives.

Lymphocyte sodium content and sodium efflux were studied in 9 healthy normotensive males without history of essential hypertension before, during and after 5 weeks of severe sodium depletion. Sodium depletion caused a significant increase in sodium content and a slight but non-significant decrease in potassium content. Total and ouabain-sensitive sodium efflux rate constants decreased significantly during sodium depletion, while absolute sodium efflux, derived from cellular sodium concentration and the corresponding sodium efflux rate constants, remained unchanged. A significant reduction in arterial mean and diastolic blood pressure, measured by ambulatory as well as by home readings, was observed during salt restriction. Prolonged severe sodium depletion of normotensive subjects leads to changes in lymphocytic sodium homeostasis, probably due to a primary inhibition of the sodium pump and a secondary intralymphocytic sodium accumulation. The mechanism underlying these changes remains unclarified.

Sodium homeostasis in lymphocytes and blood pressure alterations before and during salt restriction in normotensives and in essential hypertensives.

Blood pressure, lymphocytic sodium content and sodium efflux were studied in hypertensive and normotensive subjects during salt restriction. Diastolic blood pressure decreased significantly in both groups. In essential hypertension the initial high lymphocyte sodium content decreased during salt depletion with a simultaneous decrease in absolute sodium efflux probably due to primary changes in sodium influx. Conversely intralymphocytic sodium content increased in normotensive subjects, which may be caused by an inhibition of the sodium, potassium pump. Our findings indicate that autoregulatory mechanisms with regard to lymphocyte sodium metabolism differs between hypertensive and normotensive subjects.

Effect of oral salt loading on blood pressure and lymphocyte sodium metabolism in borderline hypertension.

A randomized double-blind cross-over trial was performed to test the effects of oral salt loading (normal diet + 200 mmol NaCl/day for 4 weeks followed by normal diet + 400 mmol/day for 1 week) against placebo on blood pressure and lymphocyte sodium homeostasis in 10 young borderline hypertensive men, genetically predisposed for essential hypertension. Salt loading caused no significant changes in blood pressure levels, lymphocyte sodium content and efflux. In conclusion, our subjects seem insensitive to a few weeks of excessive salt intake.

Lymphocyte cell membrane handling of sodium and blood pressure control during salt restriction in normotensive subjects.

Intralymphocytic sodium and potassium concentrations, 22Na efflux rate constants (EFRC) and blood pressures (BPs) were studied in nine normotensive young males without a history of essential hypertension before, during and after 5 weeks of severe sodium depletion. Diastolic and median BPs decreased significantly as estimated by both ambulatory and home readings. A slight decrease in intralymphocytic potassium content and a significant increase in sodium content was found. Measurements of 22Na-EFRC were reduced by 15% in the ouabain-sensitive component of the sodium pump, while the absolute sodium efflux stayed constant during sodium depletion. These results are evidence of a primary inhibition of the sodium pump during salt restriction in normotensives.

The chest radiograph in chronic obstructive lung disease compared with measurements of single-breath nitrogen washout and spirometry.

Postero-anterior and lateral chest radiographs were taken in 56 patients with chronic obstructive lung disease in whom the forced expiratory volume (FEV1), total lung capacity (TLC), the residual volume (RV) and the slope of phase III (S3) on the single breath nitrogen washout test (SBN2) were known. The shape and the level of the diaphragm and the shape of the costophrenic sulci, were determined from the chest films and were found to correlate with S3 and FEV1 but not TLC or RV/TLC%.

Hypercalcemia due to primary hyperparathyroidism or malignant disease. Evaluated by means of biochemical tests and the steroid suppression test.

The cortisone suppression test and some biochemical tests were evaluated in 13 patients with hypercalcemia due to primary hyperparathyroidism (PHP) and in 10 with hypercalcemia due to a malignant disease. The biochemical tests revealed that serum chloride was significantly raised in patients with PHP compared to patients with malignant diseases, whereas no differences were observed with regard to the serum values of corrected calcium, serum phosphate, chloride/phosphate ratio, HCO3-. Although serum values of parathyroid hormone were higher in patients with PHP, a consider-able overlap was observed between values in the two patient groups. Corrected serum calcium values were significantly suppressed during cortisone administration in patients with malignant disease compared to patients wit PHP, whereas prednisolone had no suppressive effect. The positive predictive value of the test was 80.0% and the negative predictive value 66.7%. We conclude that there is still no entirely reliable method to distinguish between hypercalcemia due to PHP or malignant disease.

The diagnostic value of protein clearances in rejection of human renal allografts.

The relative clearances of transferrin, haptoglobin, IgG, and IgA were used as a diagnostic test for detection of acute rejection episodes after renal transplantation, using an automated immunoprecipitin reaction. Thirty-six out of 40 rejections were predicted by 0--5 days. The sensitivity and specificity were 90% and 98%, respectively. The predictive value of a positive diagnostic test was 86% and of a negative 99%. False positives caused by fever and urinary obstruction could probably be excluded by the finding of an increased urinary excretion of beta2-microglobulin prior to the increased relative clearance of transferrin, haptoglobin, IgG and IgA. This would improve the predictive value of a positive test to 95%. Daily or more frequent protein clearance determinations should be performed in renal transplant patients, since the method used was easy, rapid and suited for sequential analysis, and the procedure was without risk for the patient.

A human albumin of placental origin (albumin Rhodia) tested for tolerance.

Fifty infusions, each containing 125 ml 20% human albumin extracted from placental tissue, were tested in clinical practice. No effects such as changes in the patient's BP, pulse rate and rectal temperature were noted during the observation period, and no side-effects such as pain, dyspnoea, nasal symptoms, exanthema or thrombophlebitis, nor any other symptoms to suggest that the solution was not well tolerated.