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Biomedical subjects

J I Scheinman

Publications and source records attributed to J I Scheinman.

At least 19 recordsLinked to original sources
PubMed1997

IgA nephropathy: to treat or not to treat?

IgA nephropathy (Berger's disease) is thought to be the most common primary glomerulonephritis in the world. Characteristically, it presents with intermittent macroscopic hematuria in association with upper respiratory infections. The diagnosis is established by demonstrating predominant IgA deposits in the glomerular mesangium. One third of the cases progress slowly over 25 years to glomerulosclerosis and end-stage renal disease. This rate of disease progression has not been altered by any known treatment, including the use of corticosteroids or cyclosporine. The pathogenesis of this disease is unknown; however, recent data implicated oxygen free radicals in the development of IgA nephropathy. The recent controlled, double-blind, 2-year study from the Mayo Clinic showed that fish oil slowed the progression of IgA nephropathy. This contrasts with the previous studies where the use of fish oil either accelerated the rate of deterioration of renal function in patients with IgA nephropathy or showed no change compared to untreated subjects. Furthermore, in experimental uremia, marked renal functional deterioration with fish oil administration has been reported. Experimental models of IgA nephropathy have been developed in the past few years. In addition, molecular biology offers an unique opportunity to study kidney tissue obtained from patients and animals with IgA nephropathy. These advances will enable the identification of the critical sequence of events that result in renal injury and provide new insight into the pathogenesis and progression of IgA nephropathy. This will help clarify the role of free oxygen radical release on disease progression, and an understanding on the mechanisms of antioxidants, such as vitamin E, in preventing such renal injury.

Animals↗
PubMed1997

Neonatal edema.

Edema develops in the neonate from diverse clinical conditions; sometimes it heralds serious underlying disorders. In this review, we discuss the diagnosis and treatment of edema in the neonate.

Edema↗
PubMed1996

Effects of uremia on growth in children.

Growth failure is a major complication of uremia in infancy and childhood. The influence of the primary renal disease leading to uremic growth retardation in children, the contributing factors leading to growth failure, such as metabolic acidosis, renal osteodystrophy, hyperparathyroidism, nutrition-endocrine and developmental disorders, are reviewed to update nephrologists on the complex issue of growth failure in children with uremia. The collaboration between endocrinologists and nephrologists in treating children with growth retardation is highlighted by a recently completed National Institutes of Health (NIH)-funded clinical trial on renal osteodystrophy plus the use of recombinant human growth hormone and insulin-like growth factor. Finally, this article concludes with a brief summary of an approach to reverse the effects of uremia on growth, including conservative nutritional management, treatment of anemia with erythropoietin, and selected aspects of growth and development after renal transplantation.

Acidosis↗
PubMed1995

The kidney in acid-base balance.

The practitioner's approach to the pediatric patient with metabolic acidosis begins with calculation of the serum anion gap, which allows the clinician to place the patient in one of two categories of acid-base disturbance: a normal anion gap acidosis or high anion gap acidosis. Likewise, the patient with metabolic alkalosis can be categorized by urinary chloride concentration and the response to chloride replenishment as either chloride-responsive or chloride-resistant. The disease states associated with each category are reviewed in this article.

Acid-Base Equilibrium↗
PubMed1995

Transplantation for primary hyperoxaluria in the USA.

US data were sought for transplantation in primary hyperoxaluria (PH). The USRDS recorded 194 patients since 1974. By lifetable analysis, survival was better for transplanted than for non-transplanted patients (P < 0.001), even after trimming data for age < 55 and end-stage renal disease since 1985 (63 patients, 39 transplanted, 24 not transplanted). Transplant survival was longer for living related donor (21) vs cadaveric (17) transplants. Twenty-nine kidney transplants in 22 children were registered in NAPRTCS. Interview data with physicians showed that eight of 17 living related donor kidneys functioned well, three were borderline and six were lost. All six cadaver kidneys were lost. Four of six kidney-liver transplants functioned, and two died. United Network for Organ Sharing recorded 13 kidney-liver transplants in 11 patients. Six initially functioned well; two were retransplanted. Ultimately seven lived and four died. Overall, transplant is better than no transplant; cadaver donation results are poor; living related kidney donation can succeed; and kidney-liver transplant is still problematic in the US, and rarely follows appropriate investigation. Until more cooperative effort can be achieved, isolated kidney living related donor transplant is preferable, and does not preclude kidney-liver transplant later.

Adolescent↗
PubMed1995

Selection of transplantation procedures and perioperative management in primary hyperoxaluria type 1.

This paper outlines the different options of transplant procedures in patients with primary hyperoxaluria type 1. Isolated kidney, isolated liver and combined liver-kidney grafting are discussed. Combined liver-kidney grafting appears to be the preferred treatment for patients already in end-stage renal failure. The potential value of the two other procedures is outlined. Guidelines for perioperative care are given. These involve fluid regime, pyridoxine supplementation, immunosuppression and administration of crystallization inhibitors such as phosphate and citrate. Special emphasis is put on selection of appropriate dialysis procedures and reasons why haemodialysis and continuous haemodiafiltration are the methods of choice.

Fluid Therapy↗
PubMed1994

Primary hyperoxaluria.

Primary hyperoxaluria (PH) is a rare inborn error of amino acid metabolism, now genetically defined, that results in excessive production and urinary excretion of oxalate. It serves as a model of severe nephrolithiasis that requires management of urinary supersaturation to prevent the common outcome of renal failure, which can be the presenting finding: the continued oxalate excess than causes progressive systemic oxalosis (deposition). Routine kidney transplantation almost invariably fails, but a (live donor) protocol that reduces danger of the accumulated load of oxalate can reduce the risk of recurrence. The attractive (and curative) option of combined kidney/liver transplant has considerably greater risk of mortality (in the US), although the European experience is considerably better, often employed earlier in the course. Key to appropriate decisions are early recognition, certain diagnosis, testing for vitamin B6 response, and immediate planning for definitive therapy when renal function is failing. PH provides one example of the absolute need for workup of the metabolic causes of stone disease.

Europe↗
PubMed1993

Enzymological and mutational analysis of a complex primary hyperoxaluria type 1 phenotype involving alanine:glyoxylate aminotransferase peroxisome-to-mitochondrion mistargeting and intraperoxisomal aggregation.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disease caused by a deficiency of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). Three unrelated PH1 patients, who possess a novel complex phenotype, are described. At the enzymological level, this phenotype is characterized by a complete, or nearly complete, absence of AGT catalytic activity and reduced AGT immunoreactivity. Unlike normal individuals in whom the AGT is confined to the peroxisomal matrix, the immunoreactive AGT in these three patients was distributed approximately equally between the peroxisomes and mitochondria. The peroxisomal AGT appeared to be aggregated into amorphous core-like structures in which no other peroxisomal enzymes could be identified. Mutational analysis of the AGT gene showed that two of the three patients were compound heterozygotes for two previously unrecognized point mutations which caused Gly41-->Arg and Phe152-->Iso amino acid substitutions. The third patient was shown to be a compound heterozygote for the Gly41-->Arg mutation and a previously recognized Gly170-->Arg mutation. All three patients were homozygous for the Pro11-->Leu polymorphism that had been found previously with a high allelic frequency in normal populations. It is suggested that the Phe152-->Iso and Gly170-->Arg substitutions, which are only eighteen residues apart and located in the same highly conserved internal region of 58 amino acids, might be involved in the inhibition of peroxisomal targeting and/or import of AGT and, in combination with the Pro11-->Leu polymorphism, be responsible for its aberrant mitochondrial compartmentalization. On the other hand, the Gly41-->Arg substitution, either in combination with the Pro11-->Leu polymorphism or by itself, is predicted to be responsible for the intraperoxisomal aggregation of the AGT protein.

Adult↗
PubMed1992

Success of kidney transplantation in oxalosis is unrelated to residual hepatic enzyme activity.

We evaluated hepatic alanine glyoxylate aminotransferase (AGT) activity in percutaneous hepatic biopsy material obtained from four children with long-term renal allograft function following transplantation for primary hyperoxaluria type 1 (PH 1). The study was performed to determine whether these successes had occurred because relatively high residual levels of AGT activity had introduced a selection bias. The children ranged from seven months to eight years at transplant and are currently well 7 to 11 years later, with no oxalate deposition on repeated allograft biopsies and creatinine clearances of 80 to 128 ml/min/1.73 m2. AGT activity ranged from 0 to 13.8%, and in two of three patients with detectable levels the AGT was in mitochondria rather than peroxisomes. These results indicate that long-term renal allograft success can occur in spite of severe AGT deficiency. Thus, the therapeutic choice of kidney alone versus combined kidney-liver transplant cannot currently be made by measuring residual hepatic AGT in PH 1. Kidney transplant alone remains a reasonable initial therapeutic alternative for patients with recent onset of renal insufficiency due to PH 1.

Adolescent↗
PubMed1992

Specialized collagen mRNA and secreted collagens in human glomerular epithelial, mesangial, and tubular cells.

Isolated glomeruli and cultured cells were examined under nonmitogenic conditions by Northern hybridization of steady-state mRNA levels for procollagens alpha 1(I), alpha 1(III), alpha 1(IV), alpha 2(IV), beta-actin, and fibronectin. Procollagens concurrently secreted from these cells were characterized after limited pepsin digestion. Poly(A)-mRNA from freshly isolated whole porcine glomeruli was primarily type IV. For cultured glomerular and tubular epithelial cells, the collagen mRNA species were almost exclusively alpha 1(IV) and alpha 2(IV). Correspondingly, the secreted collagen was almost entirely type IV. The mRNA signals for collagens in glomerular mesangial cells included alpha 1(I), alpha 1(IV), alpha 2(IV), and less alpha 1(III). The secreted collagens were also types I and IV, with less types III and V. There were similar patterns of mRNA signal levels for the two type IV collagens and similar patterns of expression of alpha 1(I) and alpha 1(III). In situ hybridization showed the fibroblast and epithelial cell populations homogeneous in expressing the same mRNA signals seen by Northern hybridization. These findings establish the correlation of collagen mRNA and protein expression of collagens in differentiated glomerular cells in culture, under resting nonmitotic conditions.

Animals↗
PubMed1991

Hyperglycaemia associated with lactic acidaemia in a renal allograft recipient with type I glycogen storage disease.

Renal disease is a frequent and serious complication of type I glycogen storage disease. A type I glycogen storage disease patient with focal segmental glomerulosclerosis and progressive renal insufficiency underwent a renal allograft transplantation. Despite the same cornstarch therapy, the post-transplantation course was complicated by worsening of the metabolic control manifested by exacerbated lactic acidaemia and hyperlipidaemia. This lactic acidaemia was remarkable for its association with hyperglycaemia. Hyperglycaemia accompanied by lactic acidaemia is strikingly unusual in type I glycogen storage disease, since this is a disease characterized by hypoglycaemia and an inverse relationship between blood glucose concentration and lactate levels. Both fasting insulin and C-peptide levels in the patient were greater than similar age-matched type I glycogen storage disease controls, indicating hyperinsulinaemia. The most likely mechanism responsible for the combined hyperglycaemia and lactic acidaemia was insulin resistance due to glucocorticoid treatment, instituted for immunosuppression. The hyperglycaemia associated with the lactic acidaemia was transient and resolved with steroid tapering. The exacerbated hyperlipidaemia, however, persisted after renal transplantation. Type I glycogen storage disease patients may be prone to glucocorticoid-induced insulin resistance, since the cellular metabolism in these patients may already be compromised with ineffective insulin action and/or reduced insulin output.

Acidosis, Lactic↗
PubMed1988

Renal disease in type I glycogen storage disease.

Although kidney enlargement occurs in Type I glycogen storage disease, renal disease has not been considered a major problem. Death from renal failure in three patients known to us prompted a study of renal function in this disorder. Of the 38 patients with Type I glycogen storage disease under our care, the 18 children under 10 years old had normal renal function. Fourteen of the 20 older patients (13 to 47 years) had disturbed renal function, manifested by persistent proteinuria; many also had hypertension, hematuria, or altered creatinine clearance. Progressive renal insufficiency developed in 6 of these 14 patients, leading to three deaths from renal failure. At the onset of proteinuria, creatinine clearance was increased in seven patients (3.05 +/- 0.68 ml per second per 1.73 m2 of body-surface area; range, 2.47 to 4.13 [normal range, 1.33 to 2.33 ml per second per 1.73 m2]). Renal biopsies were performed in three patients after an average of 10 years of proteinuria. All three biopsies demonstrated focal segmental glomerulosclerosis in various stages of progression. Our data suggest that chronic renal disease is a frequent and potentially serious complication of Type I glycogen storage disease. In addition to treating hypoglycemia vigorously, physicians should monitor renal function carefully in patients with this disorder.

Adolescent↗
PubMed1986

Immunochemistry of urinary calcium oxalate crystal growth inhibitor (CGI).

Calcium oxalate crystal growth inhibitor (CGI) was isolated from human urine in monomeric form (14,000 daltons). Antibody was elicited and purified to monospecificity by affinity chromatography. Tamm-Horsfall protein was isolated from human urine and an antibody to Tamm-Horsfall protein compared to anti-CGI. The anti-CGI reacted with its antigen on immunodiffusion, by ELISA and by Western Blotting of polyacrylamide gel electrophoresis-separated antigen. Immunofluorescent localization of CGI was found in distal renal tubules. This was precisely the localization of Tamm-Horsfall protein. Isolated Tamm-Horsfall protein was found to bind CGI which could only be partially removed with EDTA. While anti-CGI is suitable to assay CGI in human urine by ELISA techniques, it will also detect CGI that is complexed to THP. While the CGI found in human urine possesses 90% of the urinary macromolecular crystal growth inhibitor activity, THP is without effect on crystal growth, in spite of bound CGI. The balance between free CGI and that bound to Tamm-Horsfall protein may be important in the overall balance of urinary macromolecules that affect calcium oxalate nephrolithiasis.

Calcium Oxalate↗
PubMed1986

Radiological aspects of primary hyperoxaluria.

Primary hyperoxaluria is a rare metabolic disorder characterized by excessive synthesis and urinary excretion of oxalate. Nephrocalcinosis with or without calcium oxalate nephrolithiasis leads to renal failure in infancy through young adulthood. Oxalosis is the condition in which the highly insoluble calcium oxalate crystals are deposited in extrarenal tissues including bone, blood vessels, heart, and the male urogenital system. The radiographic abnormalities in 14 patients with primary hyperoxaluria are described. These abnormalities include nephrolithiasis, nephrocalcinosis, dense vascular calcifications, abnormal bone density, and characteristic metaphyseal abnormalities. Changes of renal osteodystrophy and pathologic fractures are common. Radiographic bone abnormalities are dependent on the age of the patient when renal failure occurred and the degree of success of renal transplantation. Characteristic skeletal changes are present in six of seven patients who developed renal failure when less than 7 years of age.

Adolescent↗
PubMed1986

Acute cellular rejection and cyclosporine nephrotoxicity monitored by biopsy in a renal allograft recipient. The differentiation of drug nephrotoxicity from rejection by phenotyping of cellular infiltrates.

Serial allograft biopsies were performed on a renal transplant patient who experienced recurrent episodes of acute cellular rejection as well as cyclosporine nephrotoxicity. Five biopsies were performed after acute elevations of the serum creatinine level (15, 46, 155, 244, and 324 days after transplant). Each specimen was evaluated by routine histologic techniques as well as by immunofluorescence analysis and by monoclonal antibody labeling for determination of the cell phenotype of the mononuclear cell infiltrates within each specimen. The first and third specimens disclosed significant T-cell infiltrates with an equal number of T-cytotoxic-suppressor (Leu 2a) and T-helper-inducer (Leu 3a) cells in a diffuse cortical pattern, while the second biopsy showed a slightly milder infiltrate with a marked elevation (7:1) in the Leu 3a:Leu 2a ratio in the cortical-diffuse pattern. Clinically, the patient responded dramatically to cyclosporine dosage reduction following the second biopsy, and bolus steroid antirejection therapy following the first and third biopsies. These findings suggest that phenotypic cell marker analysis within the context of histologic pattern is a useful adjunct to the routine histologic evaluation of renal allograft biopsy specimens and may provide a means of differentiating rejection from cyclosporine nephrotoxicity.

Child, Preschool↗