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Biomedical subjects

A L Friedman

Publications and source records attributed to A L Friedman.

At least 19 recordsLinked to original sources
PubMed1992

Prevention of autoimmune diabetes in the BB rat by intrathymic islet transplantation at birth.

Spontaneous diabetes in the BioBreeding (BB) rat, like human type I diabetes, results from the destruction of pancreatic islets by autoreactive T lymphocytes recognizing beta cell-specific antigens. T cell tolerance is in part mediated by interactions of maturing thymocytes with antigens expressed in the thymic microenvironment; islets were therefore implanted into the thymus of neonatal diabetes-prone BB rats to determine whether exposure of T cell precursors to beta cell antigens could influence the development of diabetes. This treatment completely prevented diabetes and insulitis in the native pancreas. The effect may be the result of specific modulation of diabetogenic T cells maturing in an islet-bearing thymus.

Animals↗
PubMed1992

A recent decrease in the time to development of monomorphous and polymorphous posttransplant lymphoproliferative disorder.

We have noted a decrease in the time to development of posttransplant lymphoproliferative disorder (PTLD) over the last two and one-half years in our multiorgan transplant program. From February 1965 until December 1990, 1622 transplants were performed including 1489 kidneys (KTxp), 87 livers (LTxp), and 46 pancreata. Between February 1965 and July 1988 (group 1), there were 1260 transplants performed and nine cases of either monomorphous PTLD (M-PTLD, n = 8) or polymorphous PTLD (P-PTLD, n = 1) were diagnosed. The mean time to development of PTLD was 163 +/- 128 weeks, all after KTxp. Five of these nine patients received haploidentical living-related grafts. All patients had presented with advanced disease, none had transplant nephrectomy, and all died of their disease. Between July 1988 and December 1990 (group 2), 362 transplants were performed, and four cases of M-PTLD and three cases of P-PTLD were recognized. Of the seven cases of PTLD in group 2, six developed within 90 days posttransplant (early PTLD). The mean time to development of PTLD was 11 +/- 16 weeks. This was significantly earlier than group 1 (P less than .01). Four of the five cases after KTxp had a 1 or 2 DR-matched donor. Five of these seven patients had serological evidence of recent Epstein-Barr Virus infection, and four of these five had received OKT3 and then developed early PTLD. In group 2, three patients are alive 7-15 months after KTxp nephrectomy, the remaining four have died. We hypothesize that risk factors for the development of PTLD may include heavy immunosuppression, including the use of OKT3, good DR matching, and active EBV infection. Treatment should include graft removal, if applicable, and reduction or cessation of immuno-suppression.

Herpesvirus 4, Human↗
PubMed1992

Vesicoureteric reflux in sibships.

A family with 4 of 6 siblings manifesting vesicoureteric reflux is presented. Reflux could not be demonstrated in preceding and succeeding generations in this family. Genetic analysis suggests that most instances of familial vesicoureteric reflux arise secondary to expression of autosomal dominant single genes with incomplete penetrance. Screening of sibships for reflux might be most appropriately carried out by urine analysis, culture and ultrasound imaging.

Child↗
PubMed1992

Effects of prolonged growth hormone administration in rats with chronic renal insufficiency.

Recombinant hGH (rhGH) augments short-term linear growth in experimental animals and children with chronic renal failure. Significant augmentation of final height, however, requires prolonged growth hormone therapy during years of growth. The effects of prolonged rhGH treatment on linear growth, progression of renal dysfunction, and longevity in the setting of renal insufficiency are unknown. We examined at 9, 15, and 25 wk growth in length and weight, glomerular filtration rate measured by inulin and creatinine clearance, food efficiency (g ingested/weight gained), and survival in treated (U-GH) and untreated (U) 75% nephrectomized uremic rats and in treated (S-GH) and untreated (S) sham-operated rats. We also measured kidney weight to body weight ratios at the time the rats were killed. Treatment was rhGH 1.0 mg s.c. three times a week during wks 4-12 of life. Length of U-GH rats was greater than that of U rats (p less than 0.05) at 15 and 25 wk (but not at 9 wk) and equal to that of S rats throughout the study. Length of S-GH rats exceeded that of S rats. At 9 wk, weight was diminished in both U and U-GH rats (p less than 0.05) versus S and S-GH rats; by 15 wk, U-GH rat weight was equal to S rat weight. Glomerular filtration rate measured by creatinine was markedly reduced in U and U-GH rats and did not increase in response to prolonged rhGH in either U-GH or S-GH rats. Diminished food efficiency of U rats versus S rats (p less than 0.05) was not improved significantly by rhGH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Renal transplantation at the University of Pennsylvania Medical Center: an update of results in the cyclosporine era.

This chapter presents a summary of living-related, living-unrelated, and cadaver renal transplantation performed at the University of Pennsylvania Medical Center between January 1984 and October 1992. Over the past 9 years, 895 patients (557 males, 338 females, mean age 42 yrs) received 942 renal transplants; 599 patients received kidneys from cadaver donors (n = 627) and 296 patients received kidneys (n = 315) from living donors of all types. During this period, 151 patients were retransplanted, sometimes more than once (159 total retransplants, 124 secondary grafts, and 35 third or more transplants). An analysis of patient ant graft survival rates (calculated by actuarial methods) for different categories of transplant recipients was performed. Black recipients, as a racial subcategory, had the poorest graft outcome, especially when followed over the long term. Graft survival rates for Black recipients who were retransplanted with cadaver grafts were even worse and were noted to be similar to the diabetic population that received cadaver retransplants (66% vs 62% at 1 yr and 32% vs 25% at 5 yrs). Diabetic recipients of living-donor transplants had excellent graft survival results, similar to nondiabetic, living-donor recipients (patient survival rates 98% and 92% vs 97% and 92% at 1 and 5 yrs; graft survival rates 92% and 82% vs 92% and 82% at 1 and 5 yrs). HLA-identical recipients of first cadaver grafts demonstrated the best outcome in the entire cadaver series (graft survival rates 91% and 83% at 1 and 5 yrs, respectively). HLA-identical recipients of second or more cadaver grafts had poorer results than expected (50% graft survival at 1 yr) despite a 100% patient survival rate. HLA-identical recipients of living-related grafts had the best graft survival rates (96% at 1 yr and 94% at 5 yrs) and superior graft survival rates for retransplanted grafts as well (100% at 1 and 5 yrs). We conclude that in the last decade, patient and graft survival rates for cadaveric and living-donor renal transplants have improved dramatically relative to the results obtained in the pre-CsA era. Long-term graft survival in Black recipients remains lower than in other races, suggesting the need to analyze other factors to explain poorer graft survival in this recipient population. Results in diabetic recipients continue to be excellent at our center, encouraging the continuation of our aggressive approach to try to transplant diabetics as early as possible, particularly when a living donor is available.

Academic Medical Centers↗
PubMed1991

Progressive renal insufficiency in methylmalonic acidemia.

Methylmalonic acidemia is a heterogeneous inborn error of propionate metabolism. Therapy frequently includes a low-protein diet to minimize precursors of methylmalonic acid (MMA) and reduce its concentration in body tissues. Renal dysfunction in these patients is increasingly recognized. Tubulointerstitial disease has been found in the small number of renal biopsy specimens from young children previously reported by others. We describe an 18-year-old patient with the mut- form of the disease who developed renal dysfunction despite the use of a low-protein diet. Tubulointerstitial injury was documented by renal biopsy. The patient had no risk factors associated with established causes of chronic tubulointerstitial nephropathy (CTIN). We postulate that methylmalonyl-CoA and/or its precursors (propionyl-CoA, odd-chain fatty acids), may be capable of producing CTIN. We speculate that prevention of renal injury may require lower tissue levels of MMA and its precursors than those required for prevention of ketoacidosis.

Adolescent↗
PubMed1991

Urinary tract malformations in identical twins.

We describe 3 sets of twins with discordance for urological malformations. Zygosity was documented by HLA and blood group typing. It is suggested that evaluation of the identical twin of an affected patient should include the entire urinary tract because of the potential for different lesions.

Blood Grouping and Crossmatching↗
PubMed1991

Renal insufficiency after bone marrow transplantation in children.

Between 1975 and 1988, 92 pediatric patients have undergone bone marrow transplantation (BMT) at our institution for malignant or immune deficiency disease. We evaluated in a retrospective fashion 64 of these patients who survived beyond the first 60 days post-BMT. The clinical course was divided into: less than 60 days post-BMT (early) and greater than 60 days post-BMT (late). The presence or absence of renal insufficiency was noted as well as all known potential factors predisposing to insufficiency. Step-wise regression analysis was then performed to determine which of the factors were most significantly associated with renal dysfunction during the two periods. The follow-up period was 2 months to 11 years (mean 17.5 months). The mean age of the patients was 7.6 years (1 month-18 years). Fifty percent of the patients had renal insufficiency during the early period and 28% of the patients had insufficiency after the initial 60 days. Three major predictors of renal insufficiency were discovered. Cyclosporin A or amphotericin B early or late post-BMT was independently predictive of developing insufficiency during the same period. Conditioning with total body irradiation was a predictor for insufficiency in both periods. Early insufficiency was not predictive of late insufficiency. Hypertension was present in 31% of patients during the early period and in 16% during the late period. Hypertension was strongly associated with cyclosporin use and renal insufficiency. Renal insufficiency is a frequent sequela in children following BMT and likely results from a combination of radiation injury and drug toxicity.

Adolescent↗
PubMed1990

Taurine depletion in very low birth weight infants receiving prolonged total parenteral nutrition: role of renal immaturity.

In a prospective, controlled study, plasma and urinary taurine concentrations were determined weekly, between postnatal weeks 3 and 18, in (1) seven sick infants (gestational age less than 28 weeks, birth weight less than or equal to 1000 gm) who received a taurine-free total parenteral nutrition solution for 32 to 49 days (group P) and who subsequently were formula fed and (2) eight sick infants matched by gestational age and birth weight, who received formula or human milk from day 3 to 4 of life (group E). Ten healthy full-term infants ranging in age from 1 to 18 weeks and fed with formula provided normal values (group C). Significantly lower mean plasma taurine values (range 1.59 to 3.43 mumol/dl) were found between postnatal weeks 3 and 7 in group P compared with group E (range 5.54 to 6.97 mumol/dl) and with group C (5.6 +/- 0.34 mumol/dl). After initiation of feeding, plasma taurine concentrations in group P increased to normal. Markedly elevated values of mean fractional excretion of taurine, 38% to 56%, were found between weeks 3 and 5 in group P and E compared with group C (15.5 +/- 3.2%). In contrast, during the same period, low urinary taurine values (4.9% to 6.7%) were found in two larger, older infants receiving total parenteral nutrition whose plasma taurine values were in the normal range. After week 5, urinary taurine values were in the control range in all groups. We conclude that the absence of taurine in total parenteral nutrition solutions administered to very low birth weight infants and the limited ability of the immature kidney to adapt to low taurine intake by "up-regulation" of tubular taurine reabsorption may result in depleted taurine body pools during the first weeks of life. This inability to conserve taurine by the immature nephron could potentially have a deleterious effect on the developing brain and retina in these infants, and indicates a possible need for taurine supplementation.

Enteral Nutrition↗
PubMed1990

Serum osteocalcin concentrations in children with chronic renal insufficiency who are not undergoing dialysis. Growth Failure in Children with Renal Diseases Study.

This report describes the serum osteocalcin values in children with mild to moderate, but relatively stable, renal dysfunction followed in the Growth Failure in Children With Renal Diseases Study. This report is derived from data obtained during the control period (6 months) before the initiation of vitamin D therapy. Up to three measurements per patient were obtained. Serum osteocalcin concentration was compared with creatinine clearance (glomerular filtration rate) calculated by the Schwartz formula; with serum concentrations of alkaline phosphatase, parathyroid hormone, and bicarbonate; and with the percentages of the recommended dietary allowances of calories and protein ingested. By standard correlation techniques, there appeared to be an inverse correlation between calculated creatinine clearance and serum osteocalcin concentration, and a direct correlation between serum osteocalcin and parathyroid hormone values. However, when we employed a statistical technique that takes into account repeated measures in the same patient, no correlation was found between calculated glomerular filtration rate and serum osteocalcin concentration, and no direct correlation was found between serum osteocalcin and parathyroid hormone values. The lack of a correlation between calculated glomerular filtration rate and serum osteocalcin values may be due to large fluctuations in the serum osteocalcin concentration, even though renal function is relatively stable.

Alkaline Phosphatase↗
PubMed1989

Two case studies from a family with primary Fanconi syndrome.

We report two cases from a family with primary Fanconi syndrome. A 39-year-old white woman with a history of frequent bone fractures developed hypophosphatemia, hypouricemia, hypokalemia, metabolic acidosis, and renal glycosuria. Her 15-year-old son had renal glycosuria without metabolic acidosis. Both had mildly to moderately impaired renal function. Determination of amino acids in 24-hour urine specimens confirmed the generalized nature of aminoaciduria. Acid-loading, bicarbonate-loading, and phosphate-loading tests revealed that the mother had proximal (type II) renal tubular acidosis and excessive renal loss of phosphate for her level of renal function. These tests for the son were normal or within normal limits of his renal function. Known causes of Fanconi syndrome, such as cystinosis and Wilson's disease, were excluded by slit-lamp eye examination and leukocyte cystine level determination. One unexpected finding in the son was the preseNce of nephrocalcinosis on x-rays; a percutaneous needle biopsy of the kidney showed tubular atrophy, interstitial fibrosis, and calcium oxalate crystal deposits. The two cases presented here represent a familial variety of the primary Fanconi syndrome, a rare entity with a limited number of cases reported in the literature.

Adolescent↗
PubMed1989

Benefit of moderate dietary protein restriction on growth in the young animal with experimental chronic renal insufficiency: importance of early growth.

Using a model of unilateral nephrectomy and contralateral heminephrectomy in weanling rats, we studied the effect of severe (6%) and moderate (14%) protein restriction on growth and renal function up to 24 wk of age. One-half the normal (N) and chronic renal insufficiency (CRI) rats underwent a cross-over protocol 6%----14% and 14%----6% at 10wk of age to analyze the contribution of early growth on ultimate wt and length. N or CRI fed a 6% protein diet were the smallest. Animals switched from 6%----14% protein diet did not catch up to their counterparts started on a 14% protein diet (N or CRI). However, N or CRI animals started on a 14% protein diet and switched to a 6% protein diet grew along a curve similar to animals fed a 14% protein diet. Creatinine clearances for CRI rats were not different among the groups. However, protein excretion was highest in those animals completing the study on a 14% protein diet. Growth failure caused by severe protein restriction occurred primarily in the early accelerated growth phase (3-10 wk). We conclude that moderate protein restriction during the early rapid growth phase maintains growth, whereas severe protein restriction is detrimental to growth. Switching to a more restrictive protein intake after the rapid growth phase did appear to offer more renal protection (lower urinary protein excretion) at the end of 24 wk. Severe protein restriction to preserve renal function is a poor strategy for the young rapidly growing individual with chronic renal disease.

Animals↗
PubMed1988

Hypomagnesemia masking the appearance of elevated parathyroid hormone concentrations in familial pseudohypoparathyroidism.

A 21-yr-old postpartum woman was found to be hypocalcemic and hypomagnesemic with a normal serum immunoreactive parathormone level (hypomagnesemic hypoparathyroidism). She was treated with calcitriol, calcium and magnesium. Two yr later the patient's son presented with tetany, hypocalcemia and the physical changes of pseudohypoparathyroidism. Subsequently, the patient's niece and nephew were also diagnosed with pseudohypoparathyroidism (low serum calcium, high serum phosphorus, high circulating immunoreactive parathormone). Re-evaluation of the patient on the above medical therapy showed a normal serum calcium, phosphorus and magnesium levels and an abnormally high serum immunoreactive parathormone level. The patient's magnesium supplementation was discontinued. No change in serum calcium, magnesium or parathormone levels resulted. We think that this patient demonstrates that hypomagnesemia can mask the laboratory presentation of pseudohypoparathyroidism by suppressing secretion of parathormone and further demonstrates that in pseudohypoparathyroidism the parathyroid gland retains its physiologic response to hypomagnesemia.

Adult↗
PubMed1988

Good outcome in prune-belly syndrome despite associated severe anomalies.

A boy aged 4.5 years with prune-belly syndrome and associated urethral stenosis, oligohydramnios, imperforate anus and vesicosigmoid fistula is described. In contrast to the anticipated poor prognosis, vesicostomy and divided transverse colostomy performed after birth followed by prophylaxis of infection and bicarbonate supplementation have resulted in a good outcome. The vesicosigmoid fistula might have served in utero as a "natural diversion" protecting from pressure-induced renal damage. It is suggested that the main determinant of prognosis in PBS is the presence and degree of kidney dysplasia at birth as reflected by the neonatal renal function after performance of an indicated urinary diversion procedure rather than the presence of severe associated anomalies.

Anus, Imperforate↗
PubMed1988

HPLC analysis of the phenylisothiocyanate (PITC) derivatives of taurine from physiologic samples.

Taurine is the major free intracellular amino acid. It has become the focus of study by many as a conjugator of bile and as a neurotransmitter and intracellular messenger. In this report we document a technique for measuring taurine in physiologic samples which is rapid, reproducible, and accurate. Any physiologic sample is first derivatized with phenylisothiocyanate (PITC) and separated by reverse phase HPLC, and then taurine is detected by UV at 254 nm. The advantages of this technique for the measurement of taurine are accuracy, small sample size, and reproducibility, and with an automated system many samples can be analyzed.

Amino Acids↗