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Biomedical subjects

R N Fine

Publications and source records attributed to R N Fine.

At least 73 records · Page 4Linked to original sources
PubMed1991

Long-term cyclosporine A treatment of steroid-resistant and steroid-dependent nephrotic syndrome.

Eighteen patients with steroid-resistant nephrotic syndrome (SRNS) and steroid-dependent nephrotic syndrome (SDNS) were treated with cyclosporine A (CyA) (6 mg/kg/d) for 2 to 29 months. CyA levels were monitored monthly and plasma levels by Abbott TDX (Therapeutic Drug Analyzer System) fluorescence polarization immunoassay were maintained at 100 to 150 ng/mL. The corticosteroid dosage administered at the time CyA therapy was initiated was variable and was continued following CyA therapy. Six of these patients (all with SDNS and minimal change nephrotic syndrome [MCNS]) had been treated with one or more courses of cytotoxic drug therapy, and all had clinical evidence of corticosteroid toxicity after receiving corticosteroid therapy for 26 to 120 months. The corticosteroid dosage was reduced by slow tapering and was ultimately discontinued in six patients. These patients were maintained on CyA monotherapy for 7 to 21 months at a dose of 3.2 to 6.7 mg/kg/d. Following 11 to 29 months of CyA therapy, seven patients underwent an elective renal biopsy, which showed nephrotoxicity in all seven. This led to discontinuation of CyA in four patients. Following discontinuation of CyA monotherapy, all four patients relapsed within 2 to 4 months. CyA therapy did not achieve a remission in 10 patients with SRNS regardless of the presence of focal segmental glomerulosclerosis (FSGS) or MCNS on renal biopsy. In conclusion, CyA has limited effectiveness in patients with SDNS who manifest corticosteroid toxicity; however, CyA should be used cautiously because of the potential for CyA nephrotoxicity and the failure to obtain a sustained remission following discontinuation of CyA monotherapy. CyA dependence is substituted for corticosteroid dependence.

Biopsy↗
PubMed1991

Growth hormone prevents steroid-induced growth depression in health and uremia.

Treatment with supraphysiological doses of corticosteroids results in protein wasting and impairment of growth, whereas exogenous growth hormone (GH) causes anabolism and improvement of growth. We wanted to know whether the growth depressing effects of methylprednisolone (MP) are more expressed in an organism which is chronically diseased and whether these effects can be counterbalanced by concomitant treatment with recombinant human growth hormone (rhGH). MP in doses from 1 to 9 mg/kg/day caused a dose dependent reduction of length gain, weight gain and weight gain/food intake ratio in 140 g healthy female Sprague-Dawley rats. Food intake was not affected by MP. This points to a change in food metabolism as a mechanism for growth impairment. In addition, treatment with MP inhibited endogenous GH secretion, documented by serum GH concentration profiles over seven hours, decreased IGF-1 serum concentration and disturbed growth cartilage plate architecture. Concomitant treatment with 2.5 to 20 IU/rhGH/kg/day prevented the negative effects of MP on growth in a dose dependent manner and normalized growth plate architecture. In uremic rats in which food efficiency and growth was already reduced, 6 mg MP/kg/day further decreased length gain and prevented weight gain completely by bringing the weight gain/food conversion ratio to the nadir. All effects of MP including reduction of muscle mass could be prevented by concomitant treatment with 10 IU rhGH/kg/day. The effects of MP and rhGH on food efficiency and growth in uremic animals were numerically nearly identical to those in pair fed ad libitum fed controls, but this may be more relevant in the diseased organism in which basal growth is already suppressed.

Animals↗
PubMed1991

Lipoproteins in children treated with continuous peritoneal dialysis.

Total lipids, lipoprotein-lipids, and apolipoproteins were studied in plasma of 20 patients, aged 13.9 +/- 3.4 y (mean +/- SD; range 7.4 to 19 y), who were treated with continuous peritoneal dialysis for a period of 2.1 +/- 1.2 (range 0.5 to 4.9) y. Measurements included total plasma cholesterol and triglycerides, triglycerides in the very low density fraction, and cholesterol in the very low density, low density, and high density fractions, as well as apo A-I and apo B. The results were compared with values in 17 healthy control subjects, aged 13.0 +/- 5.1 (range 5.1 to 19) y. The patients had significantly elevated levels of total plasma triglycerides, triglycerides in the very low density fraction, total plasma cholesterol, cholesterol in the very low density fraction, and cholesterol in the low density fraction, whereas levels of cholesterol in the high density fraction were normal. Plasma apo B levels were elevated, but apo A-I levels were not different from controls. In addition, the nutritional status of the patients was assessed and apo A-I and apo B concentrations were measured in the dialysate of 10 patients. The losses of apo A-I and apo B in dialysate averaged 13.4 +/- 7.4 and 2.1 +/- 3.1 mg/kg/d, respectively. Lipoprotein profiles were not correlated with nutritional status. We conclude that pediatric patients treated with continuous peritoneal dialysis have atherogenic lipoprotein profiles, cholesterol ratios, and apolipoprotein ratios, but normal cholesterol in the high density fraction and apo A-I levels despite considerable apo A-I losses in the dialysate.

Adolescent↗
PubMed1991

Growth hormone and the kidney: the use of recombinant human growth hormone (rhGH) in growth-retarded children with chronic renal insufficiency.

Hypothalamic production of growth hormone releasing hormone stimulates the anterior pituitary gland to release growth hormone (GH). The clinical manifestations of GH on tissues are either direct or are mediated by insulin-like growth factors (IGF). Both the somatic effects of GH and the renal manifestations of an increase in glomerular filtration rate and renal plasma flow are mediated by IGF. The increase in glomerular filtration rate/renal plasma flow that occurs with either exogenous or endogenous GH is not apparent in patients with chronic renal failure (CRF); therefore, it is unlikely that recombinant human growth hormone (rhGH) treatment of patients with CRF will result in glomerular hyperfiltration. Longitudinal studies are required to determine if the glomerulosclerosis and renal functional impairment occurring in GH and growth hormone releasing hormone transgenic mice occurs after rhGH treatment of growth-retarded uremic rats with GH resulted in an improvement in growth velocity. This led to preliminary studies in growth-retarded children with CRF by using rhGH. The acceleration of growth velocity was dramatic despite the fact that GH levels are elevated in uremia. The elevated IGF carrier proteins in uremic children may contribute to the growth retardation. Treatment with rhGH may be efficacious by stimulating a net increase in the free (unbound) IGF levels. Hyposecretion of GH may contribute to the failure to achieve optimal growth after successful renal transplantation. Treatment with rhGH may be efficacious in improving the growth velocity of renal allograft recipients.

Animals↗
PubMed1990

The 1989 report of the North American Pediatric Renal Transplant Cooperative Study.

This report of the North American Pediatric Transplant Cooperative Study summarizes data contributed by 57 participating centers on 754 children with 761 transplants from 1 January 1989 to 16 February 1989. Data collection was initiated in October 1987 and follow-up of all patients is ongoing. Transplant frequency increased with age; 24% of the patients were less than 5 years, with 7% being under 2 years. Common frequent diagnoses were: aplastic/dysplastic kidneys (18%), obstructive uropathy (16%), and focal segmental glomerulosclerosis (12%). Preemptive transplant, i.e., transplantation without prior maintenance dialysis, was performed in 21% of the patients. Dialytic modalities pretransplant were peritoneal dialysis in 42% and hemodialysis in 25%. Bilateral nephrectomy was reported in 29%. Live-donor sources accounted for 42% of the transplants. Among cadaveric donors, 41% of the donors were under 11 years old. During the first post-transplant month, maintenance therapy was used similarly for live-donor and cadaver source transplants, with prednisone, cyclosporine, and azathioprine used in 93%, 83%, and 81%, respectively. Triple therapy with prednisone, cyclosporine, and azathioprine was used in 78%, 75%, and 75% of functioning cadaver source transplants at 6 months, 12 months, and 18 months as opposed to 60%, 63%, and 54% for live-donor procedures, with single-drug therapy being uncommon. Rehospitalization during months 1-5 occurred in 62% of the patients, with treatment of rejection and infection being the main causes. Additionally, 9% were hospitalized for hypertension. During months 6-12 and 12-17, 30% and 28% of the patients with functioning grafts were rehospitalized. Times to first rejection differed significantly for cadaver and live-donor transplants. The median time to the first rejection was 36 days for cadaver transplants and 156 days for live-donor transplants. Overall, 57% of treated rejections were completely reversible although the complete reversal rate decreased to 37% for four or more rejections. One hundred and fifty-two graft failures had occurred at the time of writing, with a 1-year graft survival estimate of 0.88 for live-donor and 0.71 for cadaver source transplants. In addition to donor source, recipient age is a significant prognostic factor for graft survival. Among cadaver donors, decreasing donor age is associated with a decreasing probability of graft survival. Thirty-five deaths have occurred; 16 attributed to infection and 19 to other causes. The current 1-year survival estimate is 0.94. There have been 9 malignancies.

Adolescent↗
PubMed1990

Descriptions of the participating centers and patient population in the Growth Failure in Children with Renal Diseases Study.

The Growth Failure in Children With Renal Diseases Study, a double-blind, multicenter clinical trial with 108 children entered into the control period over 4.3 years of patient enrollment (December 1984 to April 1989), is being extended for 3 years (December 1988 to December 1991) to provide the time needed to accrue additional patients, aged between 1 1/2 and 10 years, with glomerular filtration rates of 20 to 75 ml/min/1.73 m2. The study design of randomization to two treatment arms (1,25-dihydroxyvitamin D vs dihydrotachysterol) requires a total of 108 patients with a minimum of 6 months of treatment to test the long-term effectiveness and safety of 1,25-dihydroxyvitamin D, an essential part of the therapeutic regimen for children with chronic renal insufficiency. The frequent longitudinal assessments of nutrition and growth in children with chronic renal insufficiency can better define the natural history of renal disease and its influence on growth. Similar data in the treatment period will define the impact of treatment with 1,25-dihydroxyvitamin D3 versus dihydrotachysterol on this natural history. Linear growth must be observed long enough (6 to 12 months minimum) to permit valid quantitation and comparison of the two vitamin D treatment arms, the multiple confounding variables that affect growth (e.g., steroid therapy, diabetes mellitus, prior vitamin D treatment) must be rigorously excluded or controlled, and the assignment of patients to the two groups must be random. These controls--sufficient study duration, sufficient patient numbers, and randomization--should eliminate extraneous sources of variation, including seasonal periodicity. This carefully developed, double-blind clinical trial with multiple participating centers and an effective organizational structure is coming close to achieving the goals of the study. An explosion of data regarding the natural history of chronic renal insufficiency and its treatment with vitamin D metabolites will be forthcoming at the conclusion of the study.

Child↗
PubMed1990

Technical factors contributing to successful kidney transplantation in small children.

Cadaveric renal transplantation in small children has not been as successful as either cadaver transplantation in older children, or adults, or living-related transplantation in small children. We report the results of cadaver renal transplantation in 17 children 6 years or younger with only 1 graft lost within 1 year after transplantation. The important technical factors that have enabled these improved results include careful intraoperative fluid management, use of adult kidneys with arterial anastomoses to the common iliac artery or aorta, and sequential immune suppression.

Child↗
PubMed1990

Pharmacokinetics of calcitriol in continuous ambulatory and cycling peritoneal dialysis patients.

Oral calcitriol is commonly used for the treatment of secondary hyperparathyroidism in patients undergoing long-term dialysis, but it has been suggested that intravenous (IV) or intraperitoneal (IP) administration enhances the therapeutic efficacy of the sterol. To examine potential mechanisms for this difference, the bioavailability of calcitriol was evaluated after single oral (PO), IV, and IP doses of 60 ng/kg in each of six adolescent patients with osteitis fibrosa undergoing continuous ambulatory peritoneal dialysis (CAPD) or continuous cycling peritoneal dialysis (CCPD). Serum calcitriol levels were 3.6 +/- 4.3, 8.2 +/- 7.5, and 2.5 +/- 3.0 pg/mL, respectively, before IV, PO, and IP doses of the sterol; these values increased to similar levels at 24 hours: 55.6 +/- 14.6 pg/mL after PO, 56.4 +/- 17.6 pg/mL after IV, and 53.8 +/- 20.1 pg/mL after IP. Serum calcitriol levels were higher 1, 3, and 6 hours after IV injections than after PO or IP doses; values thereafter did not differ among groups. The bioavailability of calcitriol, determined from the 24-hour area under the curve (AUC0-24) for the increase in serum calcitriol concentration above baseline values was 50% to 60% greater after IV, 2,340 +/- 523 pg.mL-1.h-1, than after PO, 1,442 +/- 467 pg.mL-1.h-1, or IP, 1,562 +/- 477 pg.mL-1.h1, dosages, P less than 0.05. These differences were due to higher values for AUC during the first 6 hours after calcitriol administration. Although IP calcitriol did not increase sterol bioavailability, radioisotope tracer studies indicated that 35% to 40% of the hormone adheres to plastic components of the peritoneal dialysate delivery system.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Effects of recombinant human erythropoietin on HLA sensitization and cell mediated immunity.

Highly presensitized patients wait longer for a renal allograft than unsensitized patients and have a poorer allograft survival rate. Repeated blood transfusions have been implicated in the induction and maintenance of sensitization. To determine the effect of recombinant human erythropoietin (rHuEPO) therapy on five transfusion dependent, highly sensitized adolescents on dialysis, we serially measured percentage panel reactive antibody (%PRA) levels, titers of identifiable discrete anti-HLA Class I antibody specificities, and non-specific indices of cellular immunity before and following initiation of rHuEPO therapy. Although four of the five patients had previously rejected at least one renal allograft, the removal of chronic antigenic stimulation from blood transfusions led to a marked reduction in anti-HLA antibody titers to recognizable private and public specificities (P less than 0.001) and a reduction of mean %PRA from 80% to 56% (P less than 0.05). Each patient demonstrated a reduction of two or more dilutions to at least two anti-HLA antibody specificities. A control group of five patients matched for age, transfusion dependence and sensitization status demonstrated no change during a comparable time interval. PHA responsiveness decreased significantly in the rHuEPO group whereas autologous and allogenic mixed lymphocyte response, spontaneous blastogenesis and T-cell subsets did not. These data indicate that in highly sensitized dialysis patients rHuEPO may lead to decreased sensitization, shorter waiting time on dialysis and possibly improved allograft survival rates.

Adolescent↗
PubMed1990

Recombinant human growth hormone treatment of children with chronic renal failure: update 1990.

Nine children with growth retardation due to chronic renal failure were treated with recombinant human growth hormone (rhGH) for 12-36 months. Results demonstrated a significant increase in height velocity at each 12-month interval compared with that achieved during the year prior to treatment. However, the increase in bone age was no greater than the increase in chronological age during the period of treatment. The mean calculated creatinine clearance did not decrease significantly during the 36 months of treatment; however, two patients required institution of dialysis at 18 and 30 months following initiation of rhGH treatment. There was no exacerbation of the glucose intolerance of uraemia following treatment. Currently, 6 of 7 patients who have been treated for more than 24 months have achieved sufficient acceleration in height velocity to attain an SDS of less than -2.00 and are above the 5th centile for chronological age on the growth curve. These updated data indicate that rhGH treatment of growth retarded children with chronic renal failure continues to result in accelerated height velocity during the second and third year of treatment, and demonstrate the potential for such children to achieve normal stature (+/- 2 SD) for chronological age despite the continued presence of chronic renal failure.

Adolescent↗
PubMed1990

Significance of the monocyte crossmatch in living-related transplantation.

It is claimed that antibodies to the vascular-endothelial (VEM) antigen system are responsible for early renal transplant rejection. To evaluate the significance of these anti-VEM antibodies, we performed a retrospective study in 16 patients aged 14.8 +/- 5 (SD) years, who received either a living-related HLA-identical (n = 5) or haplo-identical (n = 11) transplant between 4/79 and 3/84. All patients had been transfused prior to transplantation. Lymphocyte and monocyte complement dependent cytotoxic crossmatches were performed using pre- and posttransplant recipients' sera and donor lymphocytes and monocytes. Lymphocytes were isolated with Ficoll-Hypaque; monocytes by adherence to plastic Petri dishes. Of the 16 patients studied, only 1 had a positive pre- and posttransplant monocyte crossmatch. Crossmatches using recipients' T and B lymphocytes were uniformly negative, indicating the presence of anti-VEM antibodies in the absence of anti-HLA antibodies in this 1 patient. This patient rejected the transplant in the immediate posttransplant period. Of the remaining 15 patients, 4 lost their kidneys within 16 days posttransplant, whereas 11 have good graft function. We conclude that anti-VEM antibody occurs rarely pretransplant and is an unusual cause of immediate rejection in the living-related transplant situation. However, when anti-VEM antibody is identified, transplantation should be avoided because of the likelihood of immediate early rejection.

Adolescent↗
PubMed1990

Recombinant human growth hormone (rhGH) treatment of children undergoing peritoneal dialysis.

The authors studied the effect of recombinant growth hormone (rhGH) treatment on 5 growth retarded children, age 2 2/12 to 17 8/12 years, who had end-stage renal disease (ESRD) and were undergoing continuous cycling peritoneal dialysis (CCPD). Patients received 0.125 mg/kg of subcutaneous rhGH 3 times weekly. Accelerated height velocity compared to the previous year of CCPD was noted in 2 patients and improvement in the standard deviation score (SDS) as a parameter of improved growth velocity was noted in a third patient. This was associated with an increase in weight and improvement in the midarm muscle circumference (MAMC) suggesting an anabolic effect of rhGH treatment. Bone age advancement was consistent with the period of observation; no advancement greater than that expected for the increase in chronological age was observed. No significant side effects were attributable to rhGH therapy. These preliminary results indicate some growth retarded children without growth hormone deficiency with ESRD undergoing CCPD may respond to exogenous rhGH therapy with an acceleration in growth velocity: However, the failure to achieve uniform acceleration of height velocity indicates the need for controlled studies before rhGH can be recommended for all growth retarded children with ESRD undergoing peritoneal dialysis.

Adolescent↗