The usefulness of an oral calcium tolerance test in the choice of management of patients with idiopathic hypercalciuria.

We studied 40 patients with calcium urolithiasis and idiopathic hypercalciuria in an attempt to identify patients with an absorptive or renal type of hypercalciuria. An oral calcium tolerance test was performed in all patients, resulting in a rise in serum calcium in all cases (2.35 +/- 0.09 mmol/l vs 2.49 +/- 0.09 mmol/l; P less than 0.001). This was also true for serum phosphate (0.96 +/- 0.17 mmol/l vs 1.09 +/- 0.18 mmol/l; P less than 0.001), TmPO4/GFR (0.95 +/- 0.19 mmol/l vs 1.20 +/- 0.25 mmol/l; P less than 0.001) and fasting calcium excretion (3.14 +/- 1.16 mmol/100 l GF vs 6.17 +/- 2.02 mmol/100 l GF; P less than 0.001). All patients showed a drop in nephrogenous cAMP excretion (1.33 +/- 0.95 nmol/dl GF vs 0.74 +/- 0.72 nmol/dl GF; P less than 0.001). iPTH levels declined significantly (2.70 +/- 1.50 pmol/l vs 2.11 +/- 1.19 pmol/l; P less than 0.001). However, discordant individual changes in suppression of nephrogenous cAMP excretion, and rises in fasting calcium excretion prohibited a distinction between the absorptive or renal type of hypercalciuria. It is concluded that an oral calcium tolerance test is not helpful in the choice of management of patients with idiopathic hypercalciuria.

[HIV-2 infection in a Portuguese woman with an AIDS-dementia complex living in The Netherlands]. / HIV-2-infectie bij een in Nederland wonende Portugese vrouw met een AIDS-dementiecomplex.

The case history is presented of the first patient with a fatal HIV-2 infection in The Netherlands, a Portuguese woman aged 51 yr. The infection resulted in AIDS, the AIDS-dementia complex and death. Her partner, a retired Cape Verde sailor, also proved to be infected with HIV-2. Epidemiology, virology and clinical manifestations of HIV-2 infection are discussed.

Aggravation of hypoglycemia in insulinoma patients by the long-acting somatostatin analogue octreotide (Sandostatin).

Recently somatostatin analogues were successfully used to control insulin-induced hypoglycemia in patients with insulinoma. We observed a transient decrease in glucose levels and symptomatic hypoglycemia after administration of the long-acting somatostatin-analogue octreotide (Sandostatin) in two insulinoma patients. We studied the acute effects of octreotide (administered before breakfast) on blood glucose and gluco-regulatory hormones in these patients. In one patient, we studied the effects of glucagon replacement and changing the time of breakfast (relative to octreotide administration) on octreotide-associated changes in blood glucose and glucoregulatory hormones. Compared with control levels, octreotide therapy reduced insulin levels. During hypoglycemia glucagon and growth hormone levels were suppressed, but cortisol levels appropriately increased. The increase in catecholamine levels was normal in one patient, but markedly attenuated in the other. A transient decrease in serum glucose after octreotide was absent after glucagon replacement, but present when breakfast was taken before administration of octreotide. We conclude that in patients with insulinoma, octreotide therapy may be associated with clinically important hypoglycemia, during which counterregulatory hormone secretion may be attenuated.

Acute pancreatitis in a case of Werner's syndrome with severe hyperlipidaemia.

A patient with Werner's syndrome and acute pancreatitis due to severe hyperlipidaemia is reported. Special attention is paid to early recognition of the syndrome and the prevention of complications of the several metabolic disorders that occur in this syndrome.

Abnormal responsiveness of nephrogenous cyclic AMP excretion following intravenously administered calcium in normocalcaemic squamous cell cancer patients.

The renal response to calcium infusion was compared in ten normocalcaemic patients with squamous cell cancer and in ten normocalcaemic patients with adenocarcinoma. Both groups were comparable with regard to tumour load, renal function, magnesium and 25-hydroxyvitamin D levels. After injection of 3 mg elementary Ca/kg BW nephrogenous cAMP excretion fell significantly in the group of adenocarcinoma patients (1.74 +/- 1.14 nmol/dl GF vs. 2.81 +/- 1.39 nmol/dl GF; P less than 0.01) and TmPO4/GFR rose significantly at 60 and 120 min. No fall in NcAMP excretion was observed in the group of squamous cell cancer patients (2.18 +/- 0.84 vs. 2.24 +/- 0.84 nmol/dl GF; NS) and TmPO4/GFR remained unchanged. Three of ten patients with squamous cell cancer showed a paradoxical rise in NcAMP excretion following calcium administration. The other seven patients with squamous cell cancer showed a decline in NcAMP excretion (delta NcAMP) which was significantly less than in the ten patients with adenocarcinoma (0.52 +/- 0.16 vs. 1.23 +/- 0.74 nmol/dl GF; P less than 0.05). Increased phosphaturia was observed in three of ten patients with squamous cell cancer after calcium was administered. This also occurred in the presence as well as in the absence of a paradoxical activation of the adenylate cyclase system. It is concluded that the abnormal NcAMP response to calcium-infusion in normocalcaemic squamous cell cancer patients might be due to the presence of a non-suppressible PTH-like substance in these patients.

The effect of age on the renal response to PTH infusion.

The renal responses to PTH infusion were compared in two age groups of healthy subjects. Basal nephrogenous cyclic AMP (NcAMP) was higher (1.68 +/- 0.74 vs. 0.97 +/- 0.50 nmol/dl GF; P less than 0.05) and TmPO4/GFR was lower (0.93 +/- 0.21 vs. 1.16 +/- 0.14 mmol/liter; P less than 0.025) in 10 elderly subjects compared with 12 young adults. Creatinine clearance was decreased in the elderly (84.8 +/- 25.7 vs. 144.7 +/- 43.2 ml/min; P less than 0.005) and serum iPTH tended to be increased (0.15 +/- 0.11 vs. 0.11 +/- 0.03 pmol/liter). Following the infusion of 3 IU bPTH/kg bodyweight, no significant differences in delta NcAMP and delta TmPO4/GFR were seen between the groups. When responses were expressed as percentual change of basal level, elderly subjects showed a % NcAMP of 1831 +/- 1200 which was comparable with 2038 +/- 1503% in young adults. However, the percentual change in TmPO4/GFR was significantly higher in elderly persons (24.2 +/- 11.9 vs. 11.9 +/- 8.0%; P less than 0.01). In young subjects, virtually absent TmPO4/GFR responses were found in 3 cases with a relatively low basal TmPO4/GFR (between 0.92 and 0.98 mmol/liter), but these cases showed normal increases in NcAMP. Elderly subjects retained a considerable delta TmPO4/GFR notwithstanding a basal TmPO4/GFR below 0.92 in seven out of 10 cases. These results confirm the existence of a slight increase in parathyroid activity in the elderly. In addition, they suggest an augmented sensitivity of the renal tubule concerning PO4 reabsorption in elderly subjects. It is speculated that this phenomenon is related to the fall in bone mineral retention in senescence and might reflect a defense mechanism against phosphate overload.

End-organ resistance to PTH infusion in hypercalcaemic and normocalcaemic patients with solid tumours.

Ten hypercalcaemic patients with solid tumours were studied to evaluate the renal response on PTH infusion as assessed by nephrogenous cAMP excretion and maximum tubular re-absorption of phosphate. In addition, 20 normocalcaemic patients, 11 with an adenocarcinoma and 9 with a squamous cell carcinoma, were studied. All cancer patients had moderately extensive disease. Results were compared with those of 9 patients with primary hyperparathyroidism and with 10 elderly controls. All groups studied had comparable renal function, magnesium and 25-hydroxy-vitamin D levels. Comparable results were obtained in patients with an adenocarcinoma and in controls. cAMP response (delta nephrogenous cAMP) was significantly lower in the hypercalcaemic patients with a solid tumour compared with the controls (8.13 +/- 4.68 nmol/100 ml glomerular filtrate vs 29.52 +/- 25.62 nmol/100 ml glomerular filtrate; P less than 0.005). In the group of patients with primary hyperparathyroidism delta nephrogenous cAMP was 13.41 +/- 7.54 nmol/100 ml glomerular filtrate (P less than 0.06 vs controls). The group of patients with a squamous cell cancer showed an intermediate value of 14.83 +/- 10.74 nmol/100 ml glomerular filtrate (P less than 0.025 vs the normocalcaemic adenocarcinoma patients, but NS vs controls). In two hypercalcaemic patients with a solid tumour in whom PTH infusion was repeated after normalization of serum calcium no influence on renal responsiveness was observed. Responses of maximum tubular re-absorption of phosphate were lowest in the group of hypercalcaemic patients with a solid tumour and in the patients with primary hyperparathyroidism compared with controls (0.11 +/- 0.10 vs 0.22 +/- 0.09 mmol/l and 0.09 +/- vs 0.22 +/- 0.09 mmol/l; P less than 0.025 and P less than 0.005, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of pharmacological doses of calcitonin on serum beta 2 microglobulin concentration.

The effect has been studied of continuous infusion of calcitonin in 14 hypercalcemic patients and 5 patients with Paget's disease of the bones. In all hypercalcemic patients but one, a good serum calcium lowering effect was obtained. In all subjects there was a significant decrease of serum beta 2 microglobulin concentration during calcitonin infusion (4.1 +/- 3.4 vs 2.9 +/- 2.5 mg . l-1; P less than 0.01). Especially in patients with an initial increased serum beta 2 microglobulin, a pronounced decrement of this serum beta 2 microglobulin was achieved. Moreover, a positive correlation was found between the drop in serum calcium concentration and the serum beta 2 microglobulin concentration before calcitonin infusion (r = 0.83; P less than or equal to 0.01). Urinary beta 2 microglobulin excretion did not change significantly during calcitonin infusion. These results led to the speculation that the serum calcium lowering effect of calcitonin is not only the result of the direct antiosteoclastic effect of this hormone but that some immunologic modulating effect of calcitonin on the monocyte macrophage system of the bones is contributory to this hypocalcemic effect of calcitonin.

Decreased renal clearance of digoxin in chronic congestive heart failure.

Renal digoxin clearance was compared in patients suffering from atrial fibrillation with well preserved cardiac function (n = 9; salt intake +/- 170 mmol daily) and patients with chronic congestive heart failure (n = 10; salt intake 50 mmol daily and maintenance treatment with diuretics). There was no difference between the groups concerning digoxin dosage, creatinine clearance, diuresis or sodium excretion in the urine. Digoxin clearance in chronic heart failure proved to be significantly lower than in atrial fibrillation (48 +/- 21 vs 71 +/- 36 ml X min-1, p less than 0.05), and Cdig/Ccreat was similarly reduced at 0.73 +/- 0.15 compared to 1.09 +/- 0.27 (p less than 0.005). Steady state serum digoxin concentration was significantly higher in patients with congestive heart failure (1.44 +/- 0.47 vs 0.87 +/- 0.33 micrograms X 1(-1), p less than 0.01). Chronic congestive heart failure is a state with reduced digoxin clearance by the kidney, which could lead to digoxin intoxication not explicable by overdose, reduced renal function or the effect of interacting drugs.

Exercise capacity with transdermal nitroglycerin in patients with stable angina pectoris.

Transdermally delivered nitroglycerin (TTS-NTG) through a rate-controlling membrane yields stable blood levels for 24 h. We studied the effect of TTS-NTG (25 mg per 10 cm2) on exercise induced angina in 10 patients with stable angina pectoris, all in NYHA class III, who were not under treatment with other cardiac drugs. In a pre-study exercise test, all patients had angina pectoris and more than one mm ST depression. The study was placebo controlled and double blind with a randomized cross-over. Exercise tests were carried out on a treadmill according to the Bruce-protocol, 12 to 16 h after administration of TTS-NTG or of an identical placebo. After a 48 h wash-out period, the procedure was repeated after application of a plaster with the alternative content. A significant improvement was seen on TTS nitroglycerin compared with placebo in the total duration of exercise (7.2 +/- 3.6 min (mean +/- SD) vs 6.2 +/- 3.8 min; P less than 0.002). In 7 patients, the time to onset of angina was extended by TTS nitroglycerin. Maximal ST depression (lead V4 and V6) was significantly lower on TTS nitroglycerin (1.85 +/- 1 mm) compared with placebo (2.2 +/- 1 mm; P less than 0.05). It is concluded that 12 to 16 h after administration, transdermally delivered nitroglycerin improves exercise capacity and reduces maximal ST depression in patients with stable angina.

Changes in nephrogenous cyclic AMP excretion and plasma cyclic AMP following treatment of hyperthyroidism.

Plasma cyclic AMP (PcAMP) concentration and the excretion of cyclic AMP/dl GF were estimated in 11 thyrotoxic patients before and after medical treatment. PcAMP concentrations were significantly higher during hyperthyroidism (2.30 +/- 0.69 vs 1.88 +/- 0.71 nmol/dl; P less than 0.05), and total urinary cyclic AMP (TcAMP) excretion showed no significant changes (3.24 +/- 0.64 vs 3.44 +/- 1.77 nmol/dl GF). Nephrogenous (NcAMP) excretion rose significantly (1.00 +/- 0.82 vs 1.68 +/- 1.31 mmol/dl GF; P less than 0.025). The increase in NcAMP excretion correlated significantly with the decrease in serum T3 levels (r = -0.46; P less than 0.05). Serum iPTH levels showed no significant change. Both the serum Ca, corrected for serum total protein and TmPO4/GFR declined after treatment (respectively 2.44 +/- 0.13 vs 2.33 +/- 0.08 mmol/l; P less than 0.05 and 1.18 +/- 0.29 vs 1.05 +/- 0.22 mmol/l; P less than 0.05). It is concluded that the rise in NcAMP excretion corroborates the concept of increasing parathyroid activity following the treatment of hyperthyroidism.

Histamine and parathyroid activity.

The effect of histamine on parathyroid function was studied in two patients. 2.75 mg histamine phosphate administered intravenously over 120 minutes induced the well known clinical effects such as facial flushing, fall in blood pressure and increase in heart rate. But the serum calcium concentration, serum immunoreactive parathormone concentration, urinary excretion of cAMP and tubular phosphate reabsorption did not change significantly. It is concluded that stimulation of histamine receptors does not play an important role in the regulation of parathyroid activity.

Renal clearance of digoxin in man after sodium loading or furosemide treatment.

To evaluate the influence of different types of natriuresis on the renal clearance of digoxin (Cldig) and the Cldig/Clcr ratio, studies were performed in which sodium-depleted patients were placed on a moderately high sodium diet for 6 days. In another group natriuresis was evoked by furosemide. In the first study, in 10 patients, there was a 10-fold increase in Na excretion and a small rise in diuresis (V) and Clcr, which was accompanied by an increase in Cldig from 57.5 +/- 32, and 60.7 +/- 27.3 (duplicate measurements) to 103.9 +/- 55.4 (p less than 0.01) and 103.8 +/- 46.5 ml min-1 (p less than 0.01). Cldig/Clcr rose from 0.60 +/- 0.24 and 0.61 +/- 0.16 to 0.91 +/- 0.31 and 0.91 +/- 0.21, respectively (both p less than 0.005). Serum digoxin concentration declined from 1.24 +/- 0.35 and 1.19 +/- 0.40 to 1.02 +/- 0.35 and 0.97 +/- 0.32 micrograms/l (both p less than 0.01) during the high sodium diet. In the furosemide-induced natriuresis (6 patients), changes in Na excretion and V were a multiple of those caused by Na loading, but the Cldig/Clcr ratio was not increased. The results are in accordance with the concept of digoxin backdiffusion in the proximal tubules, which is dependent on proximal Na reabsorption. In the more distal segments of the nephron, where the action of furosemide occurs, there does not appear to be any transtubular movement of digoxin.