A. Vishnu Moorthy

Increased Growth after Long-Term Oral 1α,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.

Prospective trial of warfarin and dipyridamole in patients with membranoproliferative glomerulonephritis

A prospective trial of warfarin and dipyridamole was performed in patients with membranoproliferative glomerulonephritis. Eighteen completed either a control or treatment year, and 13 completed both a control and treatment year. To obviate the bias of excluding control patients who had renal failure after one year, both an unpaired and a paired analysis were performed. The unpaired analysis compared 10 patients followed for an initial control year with eight patients receiving treatment first. Renal function remained stable over the year in the treated group, but worsened in the control group. Slopes of regression lines for reciprocal serum creatinine values were significantly different between groups (p less than 0.025). Urine protein excretion also decreased in the treated group. Four of 10 control patients had a two-fold increase in serum creatinine levels, but no treatment patient did. In the paired crossover analysis, significant differences in renal function were detected between control and treatment years in six patients whose renal function significantly changed over one of the years. In every instance, there was better preservation of renal function in the treatment year. Urinary protein also decreased significantly over the treatment year compared with the control year. Bleeding was the most frequent complication. These data suggest that warfarin and dipyridamole have a beneficial effect on renal function in membranoproliferative glomerulonephritis.

Inhibition of lymphocyte blastogenesis by plasma of patients with minimal-change nephrotic syndrome.

Plasma from 7 patients with minimal-change nephrotic syndrome (M.C.N.S.) (lipoid nephrosis) confirmed by renal biopsy inhibited the blastogenic response of lymphocytes to the mitogen phytohaemagglutinin (P.H.A.) and to allogeneic lymphocytes in mixed lymphocyte culture. Plasma from 14 patients with nephrotic syndrome due to other glomerular diseases did not have this effect. 5 of the 7 patients with M.C.N.S. achieved remission; 4 with prednisone and 1 spontaneously. While in remission, plasma from these 5 patients no longer inhibited the response of lymphocytes to P.H.A. These findings suggest a pathogenic relation between M.C.N.S. and cell-mediated immunity.

Wegener granulomatosis in childhood: prolonged survival following cytotoxic therapy.

1. Jones KL, and Smith DW: The Williams elfin facies syndrome, J PEDIATR 86:718, 1975. 2. Williams JCP, Barratt-Boyes BC, and Lowe JB: Supravalvular aortic stenosis, Circular 24:1311, 1961. 3. Wiltse HE, Goldbloom RB, Antia AU, Ottesen OE, Rowe RO, and Cooke RE: Infantile hypercalcemia syndrome in twins, N Engl J Med 275:1157, 1966. 4. Illig R, and Prader A: Kasuistische Beitrage zur Idiopathischen Hypercalcemie und Vitamin D Intoxication, Helv Paediatr Acta 14:618, 1959. 5. Forfar JO: Clinical and metabolic studies in idiopathic hypercalcemia of infancy, M.D. Thesis, Scotland, 1958, University of St. Andrews, p 78 (cited in reference 6). 6. Kenny FM, Aceto T Jr, Purisch M, Harrison HE, Harrison HC, and Blizzard RM: Metabolic studies in a patient with idiopathic hypercalcemia of infancy, J P~DIATR 62:531, 1963. 7. Antia AU, Wiltse HE, Rowe RD, Pitt EL, Levin S, Ottesen OE, and Cooke RE: Pathogenesis of the supravalvular aortic stenosis syndrome, J PEDIATR 61:431, 1967.

A Syndrome of Chronic Renal Failure and XY Gonadal Dysgenesis in Young Phenotypic Females Without Genital Ambiguity

A case of XY gonadal dysgenesis with renal failure is presented. Diagnosis was delayed four years post renal transplantation. A uterus, fallopian tubes, and vagina were present with a combined gonadoblastoma and dysgerminoma found in the right streak gonad. Six other similar cases have been reported, including concordance in a pair of monozygous twins. Because of the risk of gonadal malignancy, the serum FSH concentration should be determined in phenotypic females with primary amenorrhea and chronic renal disease. Due to a physiologic reduction in the serum FSH concentration in agonadal individuals between 5 and 11 years of age, a karyotype may be required to detect affected individuals during this interval. Gonadectomy should be performed in all cases of XY gonadal dysgenesis. A urinalysis and serum creatinine concentration should be obtained in girls presenting with XY gonadal dysgenesis. The serum FSH concentration and karyotype should be determined in females presenting with congenital nephrotic syndrome.

Idiopathic Acute Interstitial Nephritis: Characterization of the Infiltrating Cells in the Renal Interstitium as T Helper Lymphocytes

A previously healthy 39-year-old man presented with acute renal failure. There was no history of exposure to drugs nor was there any infection. Renal biopsy revealed interstitial nephritis with extensive acute degenerative changes in the tubules and extensive interstitial infiltration with mononuclear cells and no eosinophils. Monoclonal antibody staining studies identified the cells in the renal interstitium to be a helper/inducer subset of T lymphocytes. We suggest that a delayed hypersensitivity mechanism played a pathogenetic role in this patients idiopathic acute interstitial nephritis.

Minimal Change Glomerular Disease: A Paraneoplastic Syndrome in Two Patients With Bronchogenic Carcinoma

Glomerulonephritis has often been reported as a paraneoplastic syndrome. In patients with carcinoma, the most common glomerular disease is membranous glomerulonephritis mediated presumably by immune complexes. Minimal change glomerular disease has been hitherto reported, to our knowledge, in only one patient with carcinoma. We report two patients with bronchogenic carcinoma in whom the simultaneous development of the nephrotic syndrome was due to minimal change glomerular disease.

“Spontaneous” Atheroembolic Disease As a Cause of Renal Failure in the Elderly*

An 86‐year‐old man with previous normal renal function was hospitalized because of renal insufficiency. He had a long history of atherosclerotic heart disease, mild hypertension and pulmonary embolism, requiring anticoagulant therapy. In view of the normal‐sized kidneys and absence of casts in the urinary sediment, a diagnosis of atheroembolic renal disease was made. The patients renal function deteriorated, but he refused hemodialysis. Death occurred within a few weeks. At autopsy, severe aortic atherosclerosis was observed and atheroembolic renal disease was confirmed as the cause of renal failure. Occasionally, renal failure can be the sole manifestation of spontaneous atheroembolic disease. This possibility should be considered if the physician is called upon to establish the diagnosis when renal insufficiency develops in atherosclerotic patients.

Distribution studies of 111in-oxine-labeled peritoneal mononuclear cells in tumor-bearing rats☆

We studied the distribution of 111In-labeled peritoneal mononuclear cells (PMC) in Sprague-Dawley rats with carcinosarcoma (CS) tumor. We obtained PMC from normal rats and rats pretreated with BCG or irradiated CS cells as antigenic stimulant. PMC were labeled in-vitro with 111In-oxine and transferred by tail-vein injection to rats bearing CS tumor. Twenty-four, 48 and 72 h after PMC transfer, we measured the accumulation of these cells in the CS tumor as a percentage of dose radioactivity per gram of tumor using an external gamma-ray camera. PMC from normal and BCG treated donor rats accumulated 0.4% and 0.46% dose per gram of CS tumor respectively. PMC from donor rats given killed CS cells accumulated significantly greater concentrations of 111In (0.79% dose per gram of CS tumor, P less than 0.025). Thus killed CS cells were able to sensitize the PMC of normal rats. 111In-oxine-labeling is an elegant procedure to study the distribution of mononuclear cells in tumors.

Tocainide pharmacokinetics during continuous ambulatory peritoneal dialysis

Abstract Tocainide hydrochloride is a class IB antiarrhythmic agent that has a long duration of action and a narrow therapeutic to toxic ratio. Although tocainide resembles lidocaine structurally, it differs in potency, lipophilicity, metabolism and pharmacokinetic profile. Tocainide is almost completely absorbed after oral administration and has a bioavailability approaching 100%. 1 It is both metabolized and excreted unchanged by the kidney. The metabolites do not exert cardioprotective or cardiotoxic effects. 2 In patients with normal renal function, the biologic half-life of tocainide is about 15 hours. 1 However, in patients with end-stage renal disease, the half-life is prolonged to approximately 23 hours. 3 Hemodialysis removes about 25% of tocainide from the body, decreasing the half-life to about 5 hours. 3 Nonrenal elimination of tocainide in end-stage renal disease appears unaffected. 3 The effect of continuous ambulatory peritoneal dialysis (CAPD) on the elimination of tocainide is unknown. This study examined selected tocainide pharmacokinetic variables in patients undergoing routine CAPD.