Concurrent sickle-cell anemia and alpha-thalassemia: effect on severity of anemia

We studied 47 patients with sickle-cell anemia to determine the effect of alpha-thalassemia on the severity of their hemolytic anemia. We diagnosed alpha-thalassemia objectively by using alpha-globin-gene mapping to detect alpha-globin-gene deletions, studying 25 subjects with the normal four alpha-globin-genes, 18 with three, and four with two. The mean hemoglobin, hematocrit, and absolute reticulocyte levels (+/- S.D.) were 7.9 +/- 0.9 g per deciliter (4.9 +/- 0.6 mmol per liter), 22.9 +/- 2.9 per cent, and 501,000 +/- 126,000 per cubic millimeter, respectively, in the non-thalassemic group; 9.8 +/- 1.6 g per deciliter (6.1 +/- 1.0 mmol per liter), 29.0 +/- 5.0 per cent, and 361,000 +/- 51,000 per cubic millimeter in the group with three alpha-globin genes; and 9.2 +/- 1.0 g per deciliter (5.7 +/- 0.6 mmol per liter), 27.5 +/- 3.0 per cent, and 100,000 +/- 15,000 per cubic millimeter in the group with two alpha-globin genes. Deletion of alpha-globin genes was also accompanied by a decreased mean corpuscular hemoglobin concentration (MCHC) in post-reticulocyte erythrocytes and by increased hemoglobin F levels. The decreased intraerythrocytic hemoglobin S concentration and elevated hemoglobin F levels associated with alpha-thalassemia appear to diminish the degree of hemolytic anemia found in sickle-cell disease.     

Sustained effectiveness of converting-enzyme inhibition in patients with severe congestive heart failure

Eight patients with severe congestive heart failure refractory to conventional therapy, including vasodilators, were given captopril (seven patients) or teprotide (one patient). All had dyspnea, edema, elevated pulmonary wedge pressure (28.0 +/- 2.6 mm Hg), low cardiac index (1.6 +/- 0.1 liters per minute per square meter), and elevated levels of serum creatinine (2.3 +/- 0.2 mg per deciliter [203.3 +/- 17.7 mumol per liter]), blood urea nitrogen (48 +/- 5 mg per deciliter [17.1 +/- 1.8 mmol of urea per liter]), plasma renin activity (21 +/- 7 ng of angiotensin I per milliliter per hour), plasma angiotensin II (271 +/- 51 pg per milliliter), and plasma aldosterone (65 +/- 14 ng per deciliter). After one week of therapy, all indexes improved. Creatinine and p-aminohippurate clearances were also increased (P less than 0.01). Improvement was sustained (more than six months) and was associated with a statistically significant increase in the cardiac ejection fraction (12 +/- 3 to 26 +/- 7 per cent). With a mean follow-up of seven months, the New York Heart Association Functional Class has been reduced from IV to II, and the number of days of hospitalization to less than 10 per cent of that before captopril therapy. We conclude that captopril reduces afterload in advanced congestive heart failure and induces sustained improvements in clinical status and renal function.     

Ten-year survival after coronary bypass surgery for unstable angina

We have assessed the long-term results of coronary bypass surgery performed for unstable angina in 1282 patients from 1970 to 1982. The operative mortality was 1.8 per cent; in the first 4 years it was 2.5 per cent, and in the last 8 1/2 years it was 1.7 per cent. Using actuarial techniques, we determined that the 5-year and 10-year survival rates (mean +/- S.E.) were 92 +/- 1 per cent and 83 +/- 2 per cent, respectively, for the whole group. For patients with "normal" left ventricular function, they were 92 +/- 2 per cent and 86 +/- 3 per cent, and for patients with "abnormal" left ventricular function 91 +/- 2 per cent and 79 +/- 4 per cent (P = 0.14). No significant differences were observed in the long-term survival for any of the three clinical subgroups of patients with unstable angina--angina at rest, angina after recovery from acute myocardial infarction, and progressive angina of recent onset (P = 0.49). The reoperation rates at 5 and 10 years were 6 +/- per cent and 17 +/- 3 per cent. Currently, 61 per cent of the survivors have no angina; angina occurs on severe exertion in 20 per cent, on ordinary exertion in 14 per cent, and on mild exertion in 5 per cent. We conclude that coronary bypass surgery is an effective form of therapy (for up to 10 years) in patients with unstable angina.     

Plasma endothelin immunoreactivity in liver disease and the hepatorenal syndrome.

BACKGROUND. Severe renal vasoconstriction is central to the pathogenesis of renal failure in the hepatorenal syndrome. Endothelin-1 and endothelin-3 are potent, long-acting vasoconstrictors, and endothelin-1 has selective potency as a renal vasoconstrictor. These properties suggest a role for endothelins in the hepatorenal syndrome. METHODS. We measured plasma endothelin-1 and endothelin-3 concentrations using specific radioimmunoassays in subjects with hepatorenal syndrome, liver disease but normal renal function, chronic renal failure, acute renal failure, liver dysfunction and renal impairment, or normal liver and kidney function. RESULTS. The patients with the hepatorenal syndrome had markedly elevated mean (+/- SE) plasma concentrations of endothelin-1 (36 +/- 5 ng per liter [14.5 +/- 1.8 pmol per liter]) and endothelin-3 (43 +/- 3 ng per liter [16.3 +/- 1.0 pmol per liter]) as compared with the normal subjects (endothelin-1, 4 +/- 1 ng per liter [1.7 +/- 0.2 pmol per liter]; and endothelin-3, 18 +/- 1 ng per liter [6.8 +/- 0.4 pmol per liter]; P < 0.001) and with the patients in the other four groups (P < 0.001 to P < 0.05). The plasma endothelin-1, but not endothelin-3, concentrations in these four patient groups were significantly higher than in the normal subjects (P < 0.001 to P < 0.05). The concentrations of endothelin-1 in renal arterial plasma and renal venous plasma, measured in five patients with the hepatorenal syndrome and three with chronic liver disease and normal renal function, were 20 +/- 4 ng per liter (7.9 +/- 1.8 pmol per liter) and 24 +/- 4 ng per liter (9.5 +/- 1.5 pmol per liter), respectively (P < 0.05). CONCLUSIONS. The increase in plasma endothelin-1 and endothelin-3 concentrations in patients with the hepatorenal syndrome is consistent with the hypothesis that these substances have a role in the pathogenesis of the disease.     

The hyperlipidemia of the nephrotic syndrome. Relation to plasma albumin concentration, oncotic pressure, and viscosity

Although hyperlipidemia is a common feature of the nephrotic syndrome, the distribution of cholesterol among the plasma lipoproteins and the mechanism of the enhanced hepatic synthesis of lipoprotein lipids are not well understood. We studied the distribution of cholesterol among the plasma lipoproteins, as well as the relation between total cholesterol and plasma albumin concentration, oncotic pressure, and viscosity in 20 consecutive adult patients with uncomplicated nephrotic syndrome. The total plasma cholesterol (mean +/- S.D., 302 +/- 100 mg per deciliter [7.8 +/- 2.6 mmol per liter]) and low-density-lipoprotein cholesterol concentrations (215 +/- 89 mg per deciliter [5.6 +/- 2.3 mmol per liter]) were elevated in most patients, but the high-density-lipoprotein cholesterol level was normal or low (46 +/- 18 mg per deciliter [1.2 +/- 0.5 mmol per liter]) in 95 per cent of the patients. Thus, many hypercholesterolemic patients with unremitting nephrotic syndrome may be at increased risk for atherosclerotic heart disease. A significant inverse correlation was found between the total plasma cholesterol concentration and both the plasma albumin concentration (r = -0.528) and the plasma oncotic pressure (r = -0.674), but not the plasma viscosity (r = +0.319). Enhanced hepatic synthesis of lipoprotein lipids may be stimulated by a decreased plasma albumin concentration or oncotic pressure but does not appear to be due to changes in plasma viscosity.     

Effects of theophylline on erythropoietin production in normal subjects and in patients with erythrocytosis after renal transplantation

BACKGROUND. Erythrocytosis occurs in 10 to 15 percent of renal-transplant recipients, and there is in vitro evidence that the production of erythropoietin is modulated by adenosine. METHODS. We prospectively evaluated the effects of theophylline, a nonselective adenosine antagonist, in eight patients with erythrocytosis after renal transplantation and in five normal controls. RESULTS. After an eight-week course of theophylline treatment, the mean (+/- SEM) serum erythropoietin levels were significantly reduced in both the renal-transplant recipients (from 60 +/- 14 units per liter at base line to 9 +/- 7 units after treatment; P less than 0.05) and the normal subjects (from 6.9 +/- 0.8 units per liter at base line to 4.7 +/- 0.5 units per liter after treatment; P less than 0.05). Similarly, the hematocrits were reduced in both the transplant recipients (from 0.58 +/- 0.04 at base line to 0.46 +/- 0.03 after treatment; P less than 0.05) and the normal subjects (from 0.43 +/- 0.01 at base line to 0.39 +/- 0.01; P less than 0.05). In the renal-transplant recipients, red-cell mass was also reduced after eight weeks of theophylline (from 3197 +/- 82 ml at base line to 2273 +/- 69 ml after treatment; P less than 0.05). The previous requirement of weekly phlebotomy was eliminated in all recipients. Plasma and urinary cyclic AMP levels were not increased. These effects were reproducible when the subjects were rechallenged with theophylline after a recovery period. CONCLUSIONS. Theophylline attenuates the production of erythropoietin in both normal subjects and patients with erythrocytosis after renal transplantation and may be useful in the treatment of the latter condition.     

An inheritable anomaly of red-cell oxalate transport in "primary" calcium nephrolithiasis correctable with diuretics

We measured the rate of oxalate flux across the red-cell membrane in the steady state in 114 patients with a history of calcium oxalate kidney stones and in 25 controls. Of the patients, 98 had recurrent, "idiopathic" kidney stones, 8 had primary hyperparathyroidism, 7 had renal or urinary tract malformations, and 1 had primary hyperoxaluria. Oxalate exchange was significantly higher in the 98 patients with idiopathic stone formation than in the controls (-1.10 +/- 0.95 [SD] X 10(-2) min-1 vs. -0.31 +/- 0.12 X 10(-2); P less than 0.001); it was above the upper limits of normal in 78 of these patients. All 8 patients with hyperparathyroidism and the patient with primary hyperoxaluria had values in the normal range; 2 of the patients with renal or urinary tract malformation had values at the upper normal limit. A study of five families indicated that the abnormality is an autosomal monogenic dominant trait with complete penetrance and variable expressivity. Oxalate-tolerance tests were carried out in five pairs of brothers. One brother in each pair had the abnormality in oxalate flux, and had a significantly higher percentage of oxalate excretion at two hours after oxalate loading (18.09 +/- 3.07 [SD] vs. 10.37 +/- 3.08 percent; t = 3.97; P less than 0.005) and four hours (14.87 +/- 2.91 vs. 9.89 +/- 2.93 percent; t = 2.70; P less than 0.05). Treatment with oral hydrochlorothiazide (50 mg per day) or amiloride (5 mg per day) or both restored normal or nearly normal red-cell oxalate exchange in all of 33 patients who initially had increased rates. We conclude that an inherited cellular defect in oxalate transport may be a factor in "primary" calcium oxalate stone formation and that this defect may be corrected with diuretics.     

Effect of strict glycemic control on renal hemodynamic response to amino acids and renal enlargement in insulin-dependent diabetes mellitus

BACKGROUND. Many patients with insulin-dependent diabetes mellitus have an increase in the glomerular filtration rate and renal enlargement early in the course of their disease. Both these changes may be risk factors for the later development of diabetic nephropathy. Their cause is not known, but they could be due to augmented renal responses to the increase in plasma amino acid concentrations that occurs when dietary protein intake is high, a factor known to increase glomerular filtration and renal blood flow in normal subjects. METHODS. We measured the glomerular filtration rate and renal plasma flow after an overnight fast and during an infusion of amino acids in 12 patients with insulin-dependent diabetes mellitus and 9 normal subjects. The diabetic patients were studied when they were hyperglycemic, when they were euglycemic after an insulin infusion for 36 hours, and after intensive insulin therapy for 3 weeks. Kidney volume was measured by ultrasonography before and after the period of intensive insulin therapy. RESULTS. The glomerular filtration rate and renal plasma flow were normal after fasting when the patients were hyperglycemic (mean [+/- SE] fasting plasma glucose level, 11.5 +/- 0.7 mmol per liter). After the amino acid infusion, these values increased more in the patients (glomerular filtration rate, 2.65 +/- 0.07 ml per second per 1.73 m2 of body-surface area; renal plasma flow, 13.30 +/- 0.68 ml per second per 1.73 m2; P less than 0.05 for both) than in the normal subjects (2.25 +/- 0.08 and 11.20 +/- 0.65 ml per second per 1.73 m2, respectively). The 36-hour infusion of insulin in the diabetic patients did not alter the glomerular filtration rate or renal plasma flow either before or during the amino acid infusion. After three weeks of intensive insulin therapy (fasting plasma glucose level, 5.3 +/- 0.2 mmol per liter), the glomerular filtration rate and renal plasma flow after the amino acid infusion (2.33 +/- 0.03 and 11.30 +/- 0.43 ml per second per 1.73 m2, respectively) were similar to those in the normal subjects. The kidney volumes in the normal subjects and the patients with diabetes were 219 +/- 14 and 312 +/- 14 ml per 1.73 m2, respectively (P less than 0.01); the volume decreased to 267 +/- 22 ml per 1.73 m2 (P less than 0.001) in the diabetic patients after three weeks of intensive insulin therapy, which was not significantly different from the volume in the normal subjects (P = 0.1). CONCLUSIONS. Conventionally treated diabetic patients who have normal renal function while fasting have augmented renal hemodynamic responses to increased plasma amino acid concentrations. The concomitant decrease in these hemodynamic responses and in kidney size with strict glycemic control suggests that these phenomena are related and influenced by the metabolic state.     

Autoantibody to the gastrin receptor in pernicious anemia

We examined serum IgG fractions from 20 patients with pernicious anemia and 25 control subjects for their capacity to inhibit binding of [125I]15-leu human gastrin-17 to parietal-cell-enriched gastric mucosal cells. IgG fractions from six patients reduced gastrin binding by 45.6 +/- 12.2 per cent, as compared with a reduction of 1.8 +/- 0.7 per cent by fractions from the 25 controls. The fractions from these six patients also reduced gastrin-stimulated [14C]aminopyrine uptake by gastric cells (an index of gastric acid secretory activity in vitro) by 50.2 +/- 8.4 per cent (mean +/- S.D.), as compared with 9.2 +/- 4.1 per cent for the controls. IgG fractions from six other patients that did not reduce gastrin binding also inhibited gastrin-stimulated [14C]aminopyrine uptake, by 48.1 +/- 9.1 per cent. These reductions in gastrin binding and aminopyrine uptake were abolished by absorption of the IgG fractions with suspensions of viable gastric mucosal cells but not by absorption with liver or kidney cells. The IgG fractions did not inhibit [3H]histamine binding or histamine-stimulated [14C]aminopyrine uptake. These results suggest that serum IgG from some patients with pernicious anemia contains autoantibodies to the gastrin receptor.     

Determination of serum immunoreactive erythropoietin in the investigation of erythrocytosis

We assessed the diagnostic value of determinations of serum levels of immunoreactive erythropoietin in 90 patients referred for the investigation of a raised packed red-cell volume (hematocrit) and possible erythrocytosis (a red-cell volume greater than that predicted by weight, body-surface area, or both). The mean values for erythropoietin were 16 mIU per milliliter (range, 8 to 22) in patients with polycythemia rubra vera (n = 24), 30 mIU per milliliter (range, 14 to 123) in patients with secondary erythrocytosis (n = 12), 27 mIU per milliliter (range, 13 to greater than 400) in patients with erythrocytosis of unknown origin (n = 19), and 25 mIU per milliliter (range, 18 to 35) in normal controls (n = 25). The values in the patients with polycythemia rubra vera were lower than those in the other three groups (P less than 0.01, P less than 0.05, and P less than 0.0001, respectively). In subjects with an increased packed red-cell volume but without erythrocytosis (n = 35), the levels of serum erythropoietin were the same as those in normal controls. Among patients with erythrocytosis with an unknown cause, abnormally high serum erythropoietin levels were found in 3 of 19 subjects, and in 1 of these 3 the abnormality was intermittent. Thus, measurement of serum erythropoietin in a single sample may be misleading and may not have high discriminatory value in distinguishing between polycythemia rubra vera and secondary erythrocytosis. This assay is useful in identifying patients with secondary erythrocytosis who have inappropriate erythropoietin secretion.     

Anemia and growth in Congolese adolescents with homozygous sickle cell anemia at Central University Hospital of Brazzaville

The rate of hemoglobin of 71 homozygous sickle cell disease patients from 10 to 18 years was studied, as well as the mean cell volume for 61 of them. Their height, weight and bone age were compared. The rate of hemoglobin in steady state is 6.5 g/dl +/- 2.3 for girls against 7.9 g/dl +/- 1.5 for boys. There's no significant difference between the rate of hemoglobin on sexual maturation state for girls. But the boys from 14 to 18 years old with signs of sexual maturation had higher rate of hemoglobin than those had not (8.5 g/dl +/- 1.3 against 6.3 g/dl +/- 1.5). Eighteen per cent of patients with homozygous sickle cell disease had a MCV superior to 100 mu 3; 57% are between 80 to 100 mu 3 and 25% under 80 mu 3. Patients with higher MCV to 100 mu 3 had low weight and height than those with inferior MCV to 80 mu 3 or 80 and 100 mu 3. Their sexual maturation is delayed with very low bone age and elevated number of hospitalisation and transfusion. Their delay of maturation was very high too. The supplementation with folic acid can lead to reduction of MCV.     

Evidence for two subtypes of Cushing's disease based on the analysis of episodic cortisol secretion

To investigate the pathogenetic mechanisms of Cushing's syndrome, we studied variations in plasma cortisol levels (episodic variations, or pulses) over 24 hours in 51 normal subjects, 14 patients with adrenal adenoma, and 46 patients with Cushing's disease. Data were obtained both from our patients and from the literature. As compared with normal subjects, patients with adrenal adenoma had fewer spikes in cortisol levels (defined as an elevation of at least 10 per cent and no less than 1 microgram per deciliter), and the spikes were lower both in absolute terms (4.0 +/- 1.8 vs. 5.1 +/- 2.2 micrograms per deciliter, P less than 0.05) and in terms of the percentage of the preceding trough concentration (23 +/- 7 vs. 123 +/- 74 per cent, P less than 0.001). Patients with Cushing's disease seemed to fall into two groups: those with hypopulsatile and those with hyperpulsatile secretion. The hypopulsatile group had a normal number and absolute height of spikes, but their height relative to the preceding trough concentration was lower than in controls (42 +/- 16 vs. 123 +/- 74 per cent, P less than 0.005). In contrast, the hyperpulsatile group had a similar number of spikes as the hypopulsatile group, but their absolute and relative heights were twice as great (12.7 +/- 2.3 vs. 6.0 +/- 1.6 micrograms per deciliter and 84 +/- 40 vs. 42 +/- 16 per cent, respectively; P less than 0.001 for both). We hypothesize that the Cushing's disease in the second group of patients may have been caused by increased hypothalamic release of, or pituitary responsiveness to, corticotropin-releasing factor, whereas that in the first group may represent pituitary oversecretion of corticotropin that is relatively independent of corticotropin-releasing factor.     

Red-cell lithium-sodium countertransport and renal lithium clearance in hypertension

Red-cell lithium-sodium countertransport is increased in patients with essential hypertension. It has been proposed that sodium-hydrogen ion exchange in the brush border of the renal proximal tubules is analogous to red-cell countertransport. To investigate the rate of sodium reabsorption by the proximal renal tubules in hypertension, we measured lithium clearance (a measure of proximal tubular reabsorption of sodium), as well as red-cell countertransport, in 14 patients with untreated essential hypertension and in 31 controls. As a group, the hypertensive patients had a higher average (+/- SEM) rate of red-cell countertransport (0.378 +/- 0.030 mmol of lithium per liter of cells per hour, P less than 0.01) and a lower renal fractional lithium clearance (13.96 +/- 0.69 percent, P less than 0.01) than normotensive subjects (0.317 +/- 0.015 mmol of lithium per liter of cells per hour and 17.75 +/- 0.81 percent, respectively). Within the normotensive group, subjects with hypertension in at least one first-degree relative had significantly lower fractional lithium clearances than subjects with no hypertensive relatives (15.37 +/- 0.84 percent vs. 19.06 +/- 1.07 percent, P less than 0.05). We conclude that hypertensive patients have heightened proximal tubular reabsorption of sodium and that red-cell countertransport is a marker of the renal abnormality. Enhanced proximal tubular sodium reabsorption may precede the development of essential hypertension.     

Accentuated vascular and endocrine response to SQ 20881 in hypertension.

We assessed vascular and hormonal responses to inhibition of peptidyldipeptide hydrolase, which converts angiotensin I to angiotensin II (converting enzyme) and degrades bradykinin (kininase II), in subjects given 10 meq of sodium to activate both systems. In nine normal subjects a threshold dose of 30 MICROgram per kilogram of the inhibitor, SQ 20881, modestly influenced mean blood pressure (-5 +/- 1 mm Hg, P less than 0.05), and renal blood flow (+50+/-8 ml per 100 g per minute), plasma renin activity (+ 2.3 +/- 0.6 ng per milliliter per hour), and angiotensin II (-11 +/- 3 pg per milliliter) more strikingly (P less than 0.01). In six patients with essential hypertension the threshold inhibitor dose was reduced to 10 microgram per kilogram; 30 kilogram per kilogram had an enhanced (P less than 0.01) effect on mean blood pressure (-11 +/- 2 mm Hg), renal blood flow (137 +/- 20 ml per 100 g per minute), and angiotensin II concentration (-29 +/- 12 pg per milliliter). SQ 20881 elevated plasma bradykinin concentration (7.4 +/- 2.6 ng per milliliter, P less than 0.02) only in the hypertensive patients. Because both renin-angiotensin and kallikrein-bradykinin systems are influenced, vascular responses to SQ 20881 must be interpreted cautiously, but this agent has excellent antihypertensive characteristics.     

Increased insulin binding to erythrocytes in anorexia nervosa: restoration to normal with refeeding.

We studied [125I] insulin binding to circulating cells in patients with anorexia nervosa (eight females), in the basal cachectic state (seven patients) and after weight gain (eight patients) and compared the values to those obtained in 17 normal volunteers (eight females and nine males). Untreated patients showed increased insulin binding to receptors on erythrocytes (mean +/- S.E.M., 12.2 +/- 0.99 per cent of total); after weight gain, these increased levels returned to normal (6.8 +/- 0.42 vs 6.7 +/- 0.63 per cent of total). Increased binding was due to an increased number of receptors per cell, with little or no change in receptor affinity. In five patients (one untreated, four treated), results of [125I] insulin binding to erythrocytes correlated closely (r = 0.982) with results obtained with monocytes. We conclude that in patients with anorexia nervosa, insulin binding to receptors is altered and that the abnormality is corrected by restoration of normal food intake and body weight.     

Treatment of acute myelogenous leukemia in children and adults

We designed a protocol to address the problem of relapse from complete remission in acute myelogenous leukemia. Patients in remission were treated for 14 months; early and later intensification of chemotherapy, sequential drug combinations, and high-dose continuous infusions of cytarabine were included. Eighty-three consecutive patients under 50 years of age were entered into this study from February 1976 to October 1979. The rate of complete remission is 70 per cent. A Kaplan-Meier analysis predicts that 49 +/- 17 per cent of patients (mean +/- 2 S.D.) who entered complete remission will remain free of disease at two years. Durations of complete remission for patients in the 0 to 17-year and 18 to 50-year age groups are comparable.     

Increased growth after long-term oral 1alpha,25-vitamin D3 in childhood renal osteodystrophy.

We evaluated oral 1,25-vitamin D3 for as long as 26 months in six prepubescent children with renal osteodystrophy previously treated with vitamin D2. Therapy was given at 14 to 41 ng per kilogram per day to correct hypocalcemia and reverse bone disease. Serum levels of 1,25-vitamin D3 were initially reduced at 15 +/- 5 pg per milliliter (mean +/- S.E.M.) and after treatment rose to 54 +/- 13. Serum calcium rose from 7.5 +/- 1.6 mg per deciliter (mean +/- S.D.) to 9.8 +/- 0.6 after one month (P less than 0.02). Alkaline phosphatase activity fell from 536 +/- 298 to 208 +/- 91 IU per liter after 12 months (P less than 0.05). Serum immunoreactive parathyroid levels fell from 900 +/- 562 microliter eq per milliliter 411 +/- 377. Healing of rickets and subperiosteal erosions was found. Remineralization of bone was demonstrated by the photon absorption technic. In four patients growth velocity, evaluated for 12 months before and after therapy, increased from 2.6 +/- 0.8 to 8.0 +/- 3.2 cm per year. Growth velocity per year increased from less than third percentile in each to the 10th to 97th percentile after therapy. Height increment ranged from 27 to 113 per cent of that expected for change in chronologic age and 40 to 114 per cent expected for change in bone age after therapy. This trial demonstrates that oral 1,25-vitamin D3 can reverse renal bone disease and increase growth in uremic children.     

Idiopathic hyperaldosteronism. A possible role for aldosterone-stimulating factor

To test the hypothesis that idiopathic hyperaldosteronism is secondary to increased adrenal stimulation by aldosterone-stimulating factor, we measured the latter in seven patients with idiopathic hyperaldosteronism and in four patients who had undergone surgical removal of an aldosterone-producing adenoma. In the patients with hyperaldosteronism, plasma aldosterone concentrations (mean +/- 1 S.E.) were 38 +/- 10 and 78 +/- 19 ng per deciliter in the supine and upright position, respectively (P less than 0.01). Supine plasma aldosterone-stimulating factor was 81 +/- 5 ng per deciliter in 15 normal subjects and 185 +/- 10 (P less than 0.01) in the patients with idiopathic hyperaldosteronism. After removal of an aldosterone-producing adenoma, plasma aldosterone-stimulating factor was normal. The supine value in each patient with idiopathic hyperaldosteronism was above the normal range (61 to 91 ng per deciliter) and increased to 290 +/- 59 ng per deciliter after four hours of upright posture. Twenty-four hour urinary excretion of aldosterone-stimulating factor was 424 +/- 35 ng (normal, 145 +/- 3; P less than 0.01) by affinity chromatography and high-pressure liquid chromatography, and it was not suppressed after two days of treatment with dexamethasone (0.5 mg orally every six hours). At the end of 48 hours, plasma concentrations were 248 +/- 40 ng per deciliter. Plasma cortisol and ACTH concentrations were under 2 micrograms per deciliter and under 40 pg per milliliter, respectively. We conclude that increased secretion of aldosterone-stimulating factor may be the cause of idiopathic hyperaldosteronism.     

Nutritional requirement for taurine in patients receiving long-term parenteral nutrition

Animals fed diets lacking the amino acid taurine have low plasma and tissue levels of taurine and ultimately have retinal dysfunction. Since parenteral nutrition does not ordinarily provide taurine, we looked for evidence of taurine deficiency in 21 children and 23 adults undergoing long-term parenteral nutrition at home for an average of 27 +/- 23 (S.D.) months. The fasting plasma taurine level was reduced in children as compared with controls (26 +/- 13 vs. 57 +/- 16 mumol per liter, P less than 0.001). In adults with less than 25 per cent intestinal absorption of the recommended caloric intake, the plasma taurine level was also significantly reduced and correlated inversely with the duration of parenteral nutrition. Electroretinograms were abnormal in each of eight children who were examined. Addition of taurine to the intravenous solutions restored plasma levels to normal in four children; the electroretinograms of three of these children also became normal. The plasma taurine level became abnormally low again in two of three children one year after the intravenous taurine was discontinued. We conclude that children and possibly adults receiving long-term parenteral nutrition have a nutritional requirement for taurine.     

Soluble IL-2 receptor and tumour necrosis factor-alpha in plasma of haemophilia patients infected with HIV.

We measured plasma concentrations of soluble receptors for IL-2 (sIL-2R) and tumour necrosis factor-alpha (TNF-alpha) in 149 haemophilia patients. Soluble IL-2R levels were elevated in 37% of 62 HIV-seronegative patients (mean 570 +/- 27 U/ml versus 361 +/- 17 U/ml in the control group, P less than 0.0001), in 78% of 68 HIV-seropositive patients (928 +/- 49 U/ml, P less than 0.0001), and in 95% of 19 AIDS/ARC patients (1578 +/- 199 U/ml, P less than 0.0001 compared with controls and with HIV-seronegative patients; P less than 0.005 compared with HIV-seropositive asymptomatic patients). A negative correlation was observed between sIL-2R, relative and absolute numbers of CD4+ cells (P less than 0.0001), and CD4/CD8 ratios (P less than 0.0001). There was also a negative correlation between sIL-2R in plasma and the cellular expression of IL-2R (P less than 0.001). We found a significant association of sIL-2R and plasma neopterin (P less than 0.0001). With progression of the disease from HIV-seronegative to seropositive without symptoms and to full manifestation of AIDS/ARC, sIL-2R plasma levels increased. The highest levels were found at the time of diagnosis of AIDS/ARC, but the levels decreased again during the following 18 months. Eight per cent of HIV-seronegative patients, 32% of HIV-seropositive patients, and 24% of patients with AIDS/ARC had increased plasma TNF-alpha. We conclude that sIL-2R and TNF-alpha plasma levels are elevated in HIV-infected haemophilia patients and that sIL-2R is a marker for disease progression from asymptomatic HIV-seropositive to AIDS/ARC.