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Biomedical subjects

F B Waldo

Publications and source records attributed to F B Waldo.

At least 19 recordsLinked to original sources

Therapy of focal and segmental glomerulosclerosis with methylprednisolone, cyclosporine A, and prednisone.

Patients with steroid-resistant focal and segmental glomerulosclerosis (FSGS) have a poor prognosis but may benefit from high-dose methylprednisolone or cyclosporine A therapy. Ten patients were treated with a protocol of methylprednisolone infusions for 8 weeks followed by a combination of cyclosporine A and alternate-day prednisone for maintenance of remission for 2 weeks. Eight of ten patients remitted the nephrotic syndrome within 8 weeks of beginning treatment. One patient remitted edema but remained proteinuric, and one did not respond. After observation for 12-24 months, seven patients maintained remission with normal glomerular filtration rate. One non-responder had renal insufficiency and one patient had secondary non-response and end-stage renal disease. No patients developed hypertension. One patient had the diagnosis of Hodgkin disease made after 10 months of therapy. Follow-up renal biopsy in four patients showed no evidence of progressive interstitial disease. There were no other major side effects. Steroid-resistant FSGS may be successfully treated with the described protocol. Additional studies will be needed to determine if this approach prevents progression of renal disease.

Adolescent↗

Effect of charcoal hemoperfusion on clearance of pentamidine isethionate after accidental overdose.

BACKGROUND: Pentamidine isethionate is an antimicrobial agent effective in the treatment of Pneumocystis carinii pneumonia, trypanosomiasis and leishmaniasis. Severe and fatal toxicity is reported with pentamidine use. CASE REPORT: A patient received an accidental overdose (40 times the prescribed dose) of intravenous pentamidine due to a pharmacy mixing error. Charcoal hemoperfusion was utilized to attempt to lower the serum concentration of pentamidine and lessen toxicity. RESULTS: Measurement of pentamidine concentrations in the patient's blood demonstrates a beneficial effect of hemoperfusion. CONCLUSIONS: Charcoal hemoperfusion may represent a useful modality in the management of pentamidine isethionate overdosage.

Antifungal Agents↗

The effect of rhGH in vitro on donor-specific hyporesponsiveness in pediatric transplantation.

Recombinant human growth hormone (rhGH) improves growth in children after renal transplantation, but may be associated with augmented immune responses. To understand the effect of rhGH in transplantation, we evaluated the role of rhGH in a mixed leukocyte culture (MLC) in vitro. We demonstrated that PBMC isolated from normal adult volunteers cultured in an MLC in the presence of rhGH develop an augmented proliferative (25-400%) and cytotoxic (50-600%) response. Using in situ hybridization (ISH), we demonstrated that the frequency of cells expressing mRNA for IFNgamma increased in the presence of rhGH (100-800%). In vitro responses of PBMC from adults in an MLC may only loosely reflect responses in vivo during pediatric transplantation. After transplantation, adults develop decreased responses to donor-specific antigens in an MLC (donor-specific hyporesponsiveness - DSH). We evaluated the donor-specific responses of 20 pediatric patients who had each received a renal allograft from one parent. Pediatric patients developed DSH similarly to adults; however, no correlation was seen between the amount of DSH and graft function. We also evaluated the expression/production of IFNgamma and IL4 in response to donor-specific alloantigens. Patients exhibit marked DSH of IFNgamma expression and production. However, IL4 production was seen in 8 out of 10 patients with normal renal function, but only 1 out of 7 patients with biopsy proven chronic rejection. Finally, we evaluated the effect of rhGH in vitro on DSH. Only 3 out of 20 patients developed augmented donor-specific responses in the presence of rhGH in vitro. rhGH augments proliferation, cytotoxicity and IFNgamma expression during an MLC. After renal transplantation, rhGH augments donor-specific responses during an MLC in some pediatric patients.

Adolescent↗

The effect of recombinant human growth hormone on responses to alloantigens in the pediatric transplant patient.

Recombinant human growth hormone (rhGH) improves growth in children after renal transplantation, but may be associated with augmented immune responses. We previously demonstrated that rhGH augments proliferative and cytotoxic responses and interferon-gamma (IFN-gamma) mRNA expression during a mixed leukocyte culture (MLC). In this study, we evaluated 12 pediatric patients after receiving a renal allograft from one of their parents. Peripheral blood mononuclear cells (PBMC) were isolated from patients and cultured with either donor or unrelated third-party PBMC in an MLC. Patients developed significant donor-specific hyporesponsiveness (DSH), however, no correlation was seen between the amount of DSH and graft function. Of the 12 patients, 2 developed augmented responses in the presence of rhGH. rhGH augments proliferation, cytotoxicity, and IFN-gamma expression during an MLC. Some patients develop increased responses to donor-specific alloantigens after renal transplantation. Further study is needed to better determine the significance of this finding.

Adolescent↗

Suppression of the immune response by nasal immunization.

Intranasal immunization results in both a mucosal and a systemic immune response in humans. Intranasal tetanus toxoid immunization in humans causes an increased serum IgA1 antibody response to tetanus toxoid following a subsequent intramuscular immunization. We hypothesized that intranasal priming with a novel protein antigen, keyhole limpet hemocyanin (KLH), would similarly result in an up-regulated systemic IgA response after a subsequent systemic immunization. To test this hypothesis, five healthy adults received a primary series of intranasal KLH immunizations followed 3 months later by a subcutaneous KLH immunizations Eight healthy adults received only a subcutaneous KLH immunization and served as controls. The nasal immunization resulted in a brisk and sustained serum IgM, IgA, and IgG antibody response and a mucosal IgA response. The subcutaneous immunization alone resulted in a serum antibody response and the development of delayed type hypersensitivity by skin testing. When the nasally primed subjects received a subsequent subcutaneous immunization there was a decline in the serum concentration of IgA and IgG antibodies to KLH. In addition, the nasally primed subjects failed to develop delayed type hypersensitivity to KLH following subcutaneous immunization. These data suggest that the nasal mucosa can induce a mucosal and systemic response; however, it may also suppress a subsequent immune response to systemic immunization.

Administration, Intranasal↗

Racial incidence of hemolytic uremic syndrome.

Hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in children and is caused by infection with verotoxin-producing Escherichia coli. There is no consensus on the relative incidence of HUS in blacks and whites. An equal racial incidence has been reported by two centers with small black populations. A series from Washington D.C. reported a low incidence in blacks. The population of Alabama is 32% black and 66% white. The Children's Hospital of Alabama admission rate has a similar racial distribution (35% black, 65% white). A record review from 1980-1992 identified 45 patients with HUS; 43 (96%) were white and only 2 (4%) were black. Based on census data for Alabama in 1980 and 1990, this gives an average annual incidence of HUS of 0.45 per 100,000 in whites and of 0.043 per 100,000 in blacks (P < 0.001, Fischer's exact test). Similar results were found in the group of patients with HUS and a history of diarrhea; whites 0.39 and blacks 0.02 (P < 0.001). However, in those with no history of diarrhea there was no significant racial difference: whites 0.05 and blacks 0.02. There were too few blacks to compare clinical course and outcome. We conclude that typical diarrhea-associated HUS is a relatively rare disease in blacks compared with whites. The reasons are unclear.

Adolescent↗

The effect of changes in dialysate volume on glucose and urea equilibration.

OBJECTIVES: To determine the effect of changing dialysate volume on urea and glucose equilibration curves and to determine, if dialysate volume is prescribed on the basis of body surface area, whether equilibrium curves will be consistent in patients of different sizes and ages. DESIGN: A prospective study wherein children with acute or chronic renal failure had peritoneal equilibrium studies done with dwell volumes of 30 mL/kg, 40 mL/kg, and 1200 mL/m2. PATIENT POPULATION: Twenty-two children: 7 under 3 years of age; 8 between 3 and 10 years of age; 7 older than 10 years of age. STATISTICS: Student's t-test. RESULTS: Urea and glucose equilibrated rapidly at dwell volumes of 30 mL/kg, slower at dwell volumes of 40 mL/kg, and slowest at dwell volumes of 1200 mL/m2. Equilibration curves were similar in children of different ages when dialysate volumes of 1200 mL/m2 were infused. CONCLUSION: Dialysate volumes of 1200 mL/m2 should be used when equilibration studies are being done to compare individuals of different ages and sizes.

Blood Glucose↗

Treatment of IgA nephropathy in children: efficacy of alternate-day oral prednisone.

We have previously reported our experience with the use of alternate-day prednisone in the treatment of 6 patients with IgA nephropathy who have clinical or pathological risk factors for disease progression. We have now treated a total of 13 patients and followed them from 4 to 10 years. Patients received an alternate-morning dose of prednisone for 2-4 years. Dosage began at 60 mg/m2 for 3 month, was reduced to 30 mg/m2 by 1 year and 15 mg/m2 by 2 years. At last observation, urinary protein excretion was normal in 12 patients and no patient had hematuria. Twelve patients had normal estimated glomerular filtration rate (GFR) and one had renal insufficiency (GFR = 38 ml/min per 1.73 m2). A renal biopsy was performed in 11 patients after 2 years of treatment. Activity score decreased from 5.2 to 4.3 (P = 0.03) and chronicity score increased from 2.2 to 2.8 (P = 0.12). There were no complications of treatment. When compared with a historical group, the treated patients had a significant improvement in urinalysis (P < 0.00001) and preservation of normal GFR (P = 0.03). We conclude that alternate-day prednisone therapy may benefit patients with IgA nephropathy. A large prospective controlled trial is needed.

Administration, Oral↗

Urine-to-blood carbon dioxide tension gradient and maximal depression of urinary pH to distinguish rate-dependent from classic distal renal tubular acidosis in children.

We determined the prevalence and clinical features of rate-dependent distal renal tubular acidosis (dRTA) in 31 children examined for possible renal tubular acidosis by measuring the urinary-minus-blood partial pressure of carbon dioxide (U-B PCO2) gradient, minimal urinary pH, and fractional excretion of bicarbonate. Of 20 patients with low U-B PCO2 gradients, nine could not lower urinary pH < or = 5.5, indicating classic dRTA, whereas 11 could lower urinary pH < or = 5.5, as described in rate-dependent dRTA. When patients with rate-dependent dRTA and classic (type I) dRTA were compared, there was no difference in the mean U-B PCO2 gradient or in clinical findings, including age, reason for referral, presence of nephrocalcinosis, or depression of linear growth. We conclude that children with rate-dependent dRTA are susceptible to at least some of the same sequelae as children with classic dRTA. Measurement of minimal urinary pH will not detect this subtle form of dRTA. Determination of the U-B PCO2 gradient should be considered a routine part of evaluation for suspected renal tubular acidosis in a child.

Acidosis, Renal Tubular↗

Treatment of growth failure in children after renal transplantation.

Growth failure continues to be a problem in the management of children with renal failure. Children have improved growth after successful renal transplantation, but seldom have "catch-up" growth, or normal adult height. In this study we report the findings of an open label pilot study to determine the safety and efficacy of the use of recombinant human growth hormone (rhGH) in children with growth failure after successful renal transplantation. Eleven children completing at least 1 year of treatment had a mean age of 11.5 years (+/- 3.3) and mean bone age of 8.4 years (+/- 2.4), and were significantly growth-retarded (mean standard deviation score of -3.18 [+1.1]). After receiving rhGH (0.05 mg/kg) subcutaneously each day the height velocity increased from 5.2 cm/year to 8.4 cm/year (P = 0.003), and the standard deviation score improved from -3.18 to -2.23 (P = 0.004). Treatment was associated with advancement in Tanner stage from 1 to 2.8 (P = 0.004), increased bone age from 8.4 years to 10.9 years (P = 0.0002), and although it was not at the point of statistical significance, moderate decrease in creatinine clearance from 75 ml/1.73m2/min to 60 ml/1.73m2/min (P = 0.1). The advancement in Tanner stage and bone age was not out of proportion to the advancement in height age. These data suggest that children with functioning renal allografts have improved growth with supraphysiologic doses of rhGH.

Adolescent↗

Pediatric renal transplantation at the University of Alabama at Birmingham, 1968 to 1993.

From May 5, 1968 through January 31, 1993, 272 renal allografts were performed in 233 children at the University of Alabama at Birmingham. Graft survival has improved since 1983 with the addition of cyclosporine. Acute and chronic rejections continue to be the major causes of graft failure. The use of living-related donor renal allografts optimizes long-term graft function, allows early transplantation, and minimizes potential long-term dialysis complications in children.

Academic Medical Centers↗

Growth hormone in the treatment of growth failure in children after renal transplantation.

Growth failure continues to be a problem in the management of children with renal failure. Children have improved growth after successful renal transplantation, but seldom have "catch-up" growth, or achieve normal adult height. Several investigators have reported the use of rhGH in children after renal transplantation and demonstrated improved height, growth velocity, and standard deviation score (SDS). We review the existing literature, present additional data from our center, and offer possible explanations.

Child Development↗

Methylprednisolone treatment of patients with steroid-resistant nephrotic syndrome.

Treatment with a combination of pulse methylprednisolone (MP) and an alkylating agent has been reported to induce long-term remission of proteinuria in patients with steroid-resistant nephrotic syndrome (SRNS). We have treated 13 patients with SRNS with a course of pulse MP. There were 8 black patients and 5 white; 10 had a biopsy diagnosis of focal segmental glomerulosclerosis (FSGS) and 3 nil lesion. Initially 5 patients responded and 2 partially responded. Of the responding patients, 5 relapsed while treated with alternate-week MP therapy. Of these relapsing patients, 3 received a second course of MP plus chlorambucil; 2 responded. The patients were observed for a mean of 47 months (range 4-64 months). When last seen only the 3 patients with a biopsy diagnosis of nil lesion were protein free. There were no complications of steroid therapy. Six patients currently have end-stage renal disease and 2 have renal insufficiency. All of the 6 patients with no response to treatment were black. These data suggest that a course of pulse MP therapy alone induces short-term remission of the nephrotic syndrome in some white patients with FSGS, but in almost no blacks. Patients who relapse may respond to retreatment, but addition of an alkylating agent does not appear to induce long-term remission in patients with FSGS.

Administration, Oral↗

Systemic immune response after mucosal immunization in patients with IgA nephropathy.

Increased IgA production has been proposed as a portion of the etiology of IgA nephropathy. Indirect human data suggest that IgG and complement may be equally important. We have immunized 17 patients with IgA nephropathy and 27 controls with tetanus toxoid. They were nasally immunized and, 2 weeks later, received an im booster immunization. This protocol has been shown to result in an increased serum IgA1 antibody response to tetanus toxin (TT). Patients had higher serum IgG antibodies to TT before and after the im immunization than did controls (pre, 42 vs 13 U; post, 155 vs 71 U; P = 0.004). Patients also had a greater increase in serum IgG antibodies (118 vs 58; P = 0.02). After the im TT, patients had lower levels of serum IgA1 antibody to TT (115 vs 180; P = 0.005) but the change in IgA1 antibodies was not significant. These data suggest that patients with IgA nephropathy may produce inappropriately large amounts of serum IgG antibodies to antigens encountered in the upper respiratory tree. Such antigens also induce a serum IgA1 response. Such a response could result in the formation of potentially nephritogenic immune complexes containing IgG, IgA1, and C3.

Administration, Inhalation↗