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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
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

Macroscopic hematuria and proteinuria preceding renal IgA deposition in patients with IgA nephropathy.

Although the clinical onset of IgA nephropathy is frequently impossible to define, macroscopic hematuria apparently heralds the onset of the disease in some patients. We describe the clinical course and renal histologic findings of four adults with IgA nephropathy who were diagnosed by the characteristic immunohistologic features in a second renal biopsy specimen. IgA was not detected in the initial renal biopsy specimens obtained 9 months to 4 years earlier. The first renal biopsy had been performed to evaluate macroscopic hematuria (recurrent in three patients), accompanied by pathologic proteinuria in two patients. Our observations suggest that the pathognomonic immunohistologic findings of IgA nephropathy may follow the clinical onset and raise questions about the presumed pathogenetic role of IgA in the early stages of this disease.

Adult↗
PubMed1991

Nasal immunization with tetanus toxoid increases the subsequent systemic dimeric IgA1 antibody response to intramuscular immunization.

We have investigated the effects of nasal immunization with tetanus toxoid (TT) on the subsequent systemic IgA response. Healthy adult volunteers who had not had a TT boost for at least five years received either an intra-muscular (IM) TT immunization alone (n = 19) or first an intra-nasal and then two weeks later an IM immunization (n = 27). The serum and circulating B cell IgG and IgA1 antibody response to TT were measured. When compared to subjects who received only an IM immunization, those who were nasally primed had increased serum levels of dimeric IgA1 antibodies to TT and an increased number of B cells secreting IgA1 antibodies to TT. These data indicate that mucosal antigen exposure is one of the mechanisms involved in the induction of systemic serum IgA1 response.

Administration, Intranasal↗
PubMed1990

Role of IgA in IgA nephropathy.

IgA nephropathy (Berger disease) is defined by the dominant or codominant deposition of IgA in the renal mesangium. There is much evidence in vitro to suggest up-regulation of the IgA immune response in patients. Data from tonsillar and bone marrow-derived lymphocytes and from in vivo immunization studies indicate that the primary defect is an up-regulated systemic one, rather than mucosal IgA production. Several lines of evidence suggest that increased IgA production alone is inadequate to explain the pathogenesis of Berger disease. Murine models of IgA nephropathy indicate that local complement activation mediated by deposited IgG is essential for mesangial cell proliferation and subsequent renal injury. Circulating immune complexes from patients with Berger disease contain IgA and IgG within the same lattice. In vitro studies of model immune aggregates containing various mixtures of IgA and IgG indicate that the IgG is the site of complement activation and fixation. The IgA in the aggregate actually inhibits both complement activation and binding to erythrocyte complement receptor CR1. This effect of IgA may prevent effective immune complex clearance. In future studies, more emphasis should be placed on the roles of IgG and complement in the pathogenesis of IgA nephropathy.

Animals↗
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↗
PubMed1989

Mixed IgA-IgG aggregates as a model of immune complexes in IgA nephropathy.

Patients with IgA nephropathy have circulating immune complexes containing IgA, IgG, and C3. We have mixed human IgG and IgA1 and heated them to form mixed aggregate. On sucrose density gradients IgG aggregates were 11 to 19S whereas IgA aggregates were either 11S or greater than 19S. Mixed aggregates had both an 19 and 11 S peak. The isoelectric point of aggregates with only IgG was 7 to 9 and of only IgA 4.5 to 5.5. The isoelectric point of mixed aggregates decreased as the percent IgA increased. IgG aggregates mixed with normal human serum caused 30% C3 activation (20 min, 37 degrees C) whereas IgA aggregates causes no activation. There was a linear decrease in C3 activation as the percent IgA increased. Mixed aggregates that contained either radiolabeled IgG or IgA were mixed with normal human serum (1 h, 37 degrees C) and then solubilized, reduced, and separated by 10% SDS-PAGE. Heavy m.w. bands, consistent with covalent bonding of C3b and C3bi to Ig H chain were only seen in lanes with labeled IgG. This was confirmed by Western blot analysis. A human dimeric IgA1 myeloma protein with rheumatoid factor activity was also studied. It caused 15% alternative pathway C3 activation but did not fix C3 to its H chain. Binding of aggregates (+/- C3) to E was tested. Aggregates with IgG C3 bound but IgA (+/- C3) did not. Addition of greater than 10% IgA to an IgG-C3 aggregate inhibited E binding. We conclude that IgG in mixed aggregates is the site of C3 fixation. In contrast, IgA does not fix C3 but instead lowers the isoelectric point, increases the size and inhibits binding to E. These properties would inhibit clearance and promote mesangial deposition and local C activation.

Antigen-Antibody Complex↗
PubMed1989

Non-specific mesangial staining with antibodies against cytomegalovirus in immunoglobulin-A nephropathy.

The glomerular staining of a commercial polyclonal antiserum against cytomegalovirus (CMV) and of a mixture of 13 monoclonal anti-CMV antibodies in twelve patients with immunoglobulin-A (IgA) nephropathy was examined. The polyclonal antiserum stained the mesangium in all patients. The CMV staining coincided only partially with that of IgA in five patients and the staining distributions were discordant in six. The monoclonal antibodies stained mesangium in only one patient. Serum levels of IgA and IgG anti-CMV antibodies did not differ between patients and controls. In western blot analysis, the polyclonal antiserum reacted with three proteins in uninfected human fibroblasts. Absorption of the antiserum with uninfected fibroblasts reduced the reactivity on western blot analysis and eliminated glomerular staining in five of six renal biopsy samples. It is concluded that the previously reported binding of anti-CMV antibodies to glomeruli from patients with IgA nephropathy may be the result of contaminating antibodies to human antigens.

Antibodies, Monoclonal↗
PubMed1989

Zinc and copper balance in children on continuous ambulatory peritoneal dialysis.

We monitored serum zinc and copper levels for 4 months in six patients treated with continuous ambulatory peritoneal dialysis (CAPD). Zinc and copper fluxes were studied during a single dialysis exchange and over a 3-day period. Routine oral trace element supplements were then discontinued for 2 months. Serum zinc levels declined but serum copper levels remained unchanged. One month after oral supplements had been restarted, serum zinc levels returned to normal and serum copper levels rose above initial values. Zinc and copper concentrations in dialysis exchange indicated that the patients absorbed zinc and lost copper in significant amounts. The patients had poor dietary intakes of both minerals. These data suggest that patients treated with CAPD benefit from oral zinc supplementation.

Adolescent↗
PubMed1989

Alternate-day prednisone therapy in children with IgA-associated nephritis.

IgA nephropathy (IgAN) leads to renal failure in up to 30% of affected children and adults. There is currently no consensus on therapy in IgAN. Six patients with risk factors for disease progression were identified based on clinical or histologic findings. These patients were treated with alternate-day prednisone for 12 to 60 (mean, 36) months and followed for 28 to 60 (mean, 54) months. Follow-up biopsies were available in four patients. At last examination all treated patients had normal urinalysis and serum creatinine level. Follow-up biopsies showed stable or improved glomerular histology in three of four patients. One patient had a slight worsening of the interstitial disease. No steroid toxicity was observed. The outcome of these treated patients was compared with that of 15 comparable patients from another center who received no treatment and with patients from two published clinical pathology series. A normal urinalysis was found at follow-up in all treated patients, compared with one of 15 untreated patients (P = 0.003). None of the patients in the published series with comparable disease had normal urinalysis at follow-up. End-stage renal disease or renal insufficiency occurred in seven of 15 untreated and no treated patients (P = 0.19). The data strongly support the need for a prospective control trial of prednisone therapy in IgAN.

Adolescent↗
PubMed1989

Systemic immune response to oral polio immunization in patients with IgA nephropathy.

The systemic immune response to a booster dose of attenuated polio vaccine has been studied in a group of patients with IgA nephropathy, their parents and healthy unrelated controls. The serum IgA and IgG antibody response and the antibody response in cultured lymphocyte supernatants was quantitated by a sensitive radio-immunoassay. Three of eight patients and two of their parents had elevated serum IgA antibody to polio pre-immunization. There was no significant rise in serum IgA or IgG antibody to polio post-immunization in any group. However, the five subjects with elevated pre-immunization levels fell into the normal range post-immunization, suggesting IgA specific suppression. Total and antigen specific IgA rose post-immunization in culture supernatants in all groups. The rise did not differ among the groups. The patients and parents with high serum antibody also had high culture supernatant levels and these fell post-immunization. There was an increased antigen non-specific IgG response in four patients and three of their parents. The data provide additional in vivo evidence of an upregulated IgA immune response in patients with IgA nephropathy. In addition, the data provide the first in vivo evidence of aberrant immune responses in the first degree relatives of patients with IgA nephropathy. This appears to be one of perhaps several inherited traits which may predispose an individual to develop this common and progressive nephropathy.

Administration, Oral↗