T-lymphocyte subsets in nephrotic syndrome.

T-lymphocyte subsets when measured in steroid responsive nephrotic syndrome (SRNS) have demonstrated significant variance from normal values. T-cell subsets were studied by using two-color flow cytometric analysis in 32 children (9.2 +/- 5 years of age) with SRNS. The children were divided into four groups: a) SRNS in acute relapse, on prednisone; b) SRNS in acute relapse, off prednisone; c) SRNS in long-term remission, off prednisone (nephrotic controls); d) patients in remission on long-term prednisone therapy; and e) 15 age-matched normal controls. Children suffering an acute relapse of SRNS showed an increase in Leu2a+/DR+ (CD8) activated lymphocytes (P less than 0.05), a decrease in Leu4a+ total T-lymphocytes (P = 0.01) and a decrease in Leu3a+ (CD4) helper T-cells (P less than 0.05) when compared to normal controls and nephrotic controls. Though some subset changes may represent a prednisone effect and the functional role of these lymphocytes in the disease process is unknown, this study provides additional evidence to support a role for abnormal T-cell subsets in the etiology of SRNS.

Increased circulating concentration of the N-terminus of the atrial natriuretic factor prohormone in persons with pheochromocytomas.

To investigate the possible relationship of hypertension and the N-terminus of the atrial natriuretic factor (ANF) prohormone which contains two peptides [i.e. pro ANF-(1-30) and pro-ANF-(31-67)] with blood pressure-lowering effects, we examined the circulating levels of the N-terminus of the ANF prohormone in three patients with pheochromocytomas before surgery, during an increase in their blood pressure with surgical manipulation of their tumors, and after surgery when their blood pressures returned to normal. The circulating levels of the whole N-terminus [amino acids 1-98; pro-ANF-(1-98)] and pro-ANF-(31-67) from the midportion of the N-terminus of the ANF prohormone were increased 2-fold in patients with both extraadrenal and intraadrenal pheochromocytomas. In both the intraadrenal and extraadrenal patients N-terminus [pro-ANF-(1-98)] and pro-ANF-(31-67) circulating levels increased further during surgical manipulation and returned to normal after surgical removal of their respective tumors. Each of these pheochromocytomas was found to have pro-ANF-(1-30) and -(31-67)-binding sites that were functional, since they could enhance the guanylate cyclase-cGMP system 2-fold in these pheochromocytomas. The entire 126 amino acids of the prohormone were present within each of the pheochromocytomas, since both the whole N-terminus and C-terminus (i.e. ANF) of the prohormone were present. Examination of the pheochromocytomas by electron microscopy revealed electron-dense granules similar to those in the heart, which have been associated with the synthesis and storage of the ANF prohormone. We conclude that 1) the whole N-terminus [pro-ANF-(1-98)] and pro-ANF-(31-67) of the ANF prohormone circulate at higher concentrations in persons with pheochromocytomas and return to normal with removal of the tumors; 2) pheochromocytomas contain specific binding sites for pro-ANF-(1-30) and -(31-67); 3) these binding sites are functional, since pro-ANF-(1-30) and -(31-67) could enhance the enzyme guanylate cyclase within these tumors; and 4) the entire 126 amino acids of the ANF prohormone are present within these tumors, which have electron-dense granules associated with polypeptide hormone synthesis, suggesting that the ANF prohormone is being synthesized within the pheochromocytomas.

Localization of adrenal and extra-adrenal pheochromocytomas by magnetic resonance imaging.

We found magnetic resonance imaging helpful in the localization of both an adrenal and an extra-adrenal pheochromocytoma, since these tumors produced a high-intensity "light bulb" image. MRI is an excellent method for localizing pheochromocytomas because it detects adrenal and extra-adrenal pheochromocytomas missed by computerized tomography and adrenal-renal ultrasonography, and because the high-intensity MRI signal generated by pheochromocytomas is useful in differentiating them from nonfunctioning adrenal masses in hypertensive patients.

Increased circulating concentration of atrial natriuretic factor in persons with pheochromocytomas.

To investigate the possible relationship of atrial natriuretic factor (ANF) to hypertension, we examined the circulating levels of ANF in 3 patients with pheochromocytomas before surgery, during increase of their blood pressure with surgical manipulation of their tumors, and after surgery when their blood pressures returned to normal. The circulating levels of ANF were increased 2-fold in patients with both extra-adrenal and intra-adrenal pheochromocytomas. In both the intra-adrenal and extra-adrenal patients their ANF levels increased further during surgical manipulation and returned to normal after surgical removal of their respective tumors. Each of these pheochromocytomas was examined and found to have atrial natriuretic receptors that were functional since ANF could enhance the guanylate cyclase - cyclic GMP system two-fold in these pheochromocytomas. We conclude that ANF circulates at higher concentrations in persons with pheochromocytomas and returns to normal with removal of the tumor. In addition, pheochromocytomas contain specific ANF receptors and ANF itself within these tumors.

Thrombotic thrombocytopenic purpura in an asplenic patient with hereditary spherocytosis: failure of plasmapheresis, antiplatelet therapy, and corticosteroids.

Thrombotic thrombocytopenic purpura (TTP) is a severe multisystem disorder characterized by microangiopathic hemolysis, central nervous system and renal dysfunction, and a very poor prognosis. Recently, however, plasma exchange or infusion therapy has proven effective in the majority of patients with TTP. We report a patient who developed TTP several years after splenectomy for hereditary spherocytosis. Despite aggressive therapy with plasmapheresis (PP), plasma infusion, antiplatelet drugs, and corticosteroids, the patient had progression of TTP that eventually resulted in his death. The occurrence of TTP in an asplenic patient with an intrinsic red cell disorder, a previously unreported association, may predict a poor prognosis.

Fanconi syndrome in a patient with a variant of isovaleric acidemia.

Fanconi syndrome with proximal renal tubular acidosis is caused by a variety of anatomic, functional and metabolic disorders. We report a patient with a variant of isovaleric acidosis who developed proximal tubular acidosis. This patient was able to acidify the urine during metabolic acidosis, developed a hyperchloremic metabolic acidosis, and needed 24 mEq/kg/day of bicarbonate to maintain normal serum bicarbonate. She had a FE Bicarbonate of 12 +/- 4% during bicarbonate infusion. Isovaleric acidosis may be another toxic cause of proximal RTA.

Ureteropelvic junction obstruction presenting with recurrent abdominal pain: diagnosis by ultrasound.

Three cases of ureteropelvic junction obstruction are presented in which the only symptom was recurrent abdominal pain. Results of physical examination and urinalysis were normal. Ultrasound established the correct diagnosis in the two patients in whom it was performed. Because it is safe, involves no radiation exposure, and is useful in evaluating the gallbladder, pancrease, and liver, as well as both kidneys, abdominal ultrasound should be performed prior to contrast radiography in the evaluation of children with recurrent abdominal pain.

Somatomedin in children with chronic renal insufficiency - relationship to growth rate and energy intake.

The relationship of energy intake, growth rate and serum concentration of somatomedin-A was evaluated in eighteen children with chronic renal insufficiency. Serum concentrations of somatomedin-A were found to be 0.84 micro/ml in normal children and were elevated to 3.06 micro/ml in children with chronic renal insufficiency prior to dialysis (p less than 0.01). Somatomedin-A concentrations increased during chronic hemodialysis to 5.81 micro/ml and decreased to 1.59 micro/ml following successful renal transplantation (p less than 0.01). Serum concentrations of somatomedin-A correlated with residual glomerular filtration rates (r = -0.5), serum creatinine concentration (r = 0.59), and blood urea nitrogen (r = 0.6). Growth rates correlated with energy intake (r = 0.58) and somatomedin-A concentrations (r = 0.4) in the children with chronic renal insufficiency. Both energy intake and somatomedin-A increased significantly after one year of nutritional supplementation. Our findings are consistent with the hypothesis that somatomedin, like other polypeptide hormones, is elevated in uremia and that increased energy intake may affect the growth of children with chronic renal insufficiency by increasing somatomedin levels.

Chronic camphor ingestion mimicking Reye's syndrome.

Camphor is a potentially dangerous drug which nevertheless remains popular as a home remedy. Because of its hepatoneurotoxic effects, camphor toxicity may clinically mimic Reye's syndrome. The differentiation between the two requires histologic examination of liver tissue, further emphasizing the need for a liver biopsy to establish the diagnosis of Reye's syndrome.

Growth impairment with elevated somatomedin levels in children with chronic renal insufficiency.

In children with chronic renal insufficiency serum levels of somatomedin measured by radioreceptor assay were found to be strikingly elevated and were in the same range as in acromegaly in spite of decreased growth. The serum somatomedin level was inversely correlated with renal function and children on haemodialysis had the highest values. The elevated somatomedin was most likely due to progressive destruction of the kidney, the primary catabolic site for somatomedin and other polypeptides. After successful transplantation the somatomedin values fell to slightly above normal even though growth was still impaired. Using a bioassay based on the mitogenic property of somatomedin, a lower than normal rather than an increased level was found in chronic renal insufficiency suggesting that in uraemia an inhibitor to somatomedin bioactivity was present. It is concluded that the cause of the growth failure in chronic renal insufficiency and after transplantation is not due to a lack of somatomedin, but an inhibitor to its action could be a factor. It would appear that a normal somatomedin may be necessary for normal growth, but it is not sufficient.