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Biomedical subjects

B A Fivush

Publications and source records attributed to B A Fivush.

At least 37 records · Page 2Linked to original sources
PubMed1997

Varicella in the first year after renal transplantation: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

Prior reports document that children with renal transplants are at risk of severe varicella, with a 5-25% mortality rate. We have examined the current incidence and mortality of varicella requiring hospitalization in pediatric patients in the first year after kidney transplantation through a multi-center retrospective cohort study. Data from the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) for 2320 pediatric patients who received renal transplants between 1987 and 1993 and were followed until 1995 were examined. Varicella requiring hospitalization in the first post-transplant year occurred in 44 children. Characteristics of the patients who developed varicella were compared to the rest of the NAPRTCS cohort using chi-square analysis. Kaplan-Meier estimates of graft survival were used to compare graft survival in varicella patients and other NAPRTCS patients. Varicella patients tended to be younger (p=0.09) and more often male (p=0.07, chi-square) than other NAPRTCS patients. None of the 44 patients with varicella in their first post-transplant year died from this infection. The number of episodes of acute rejection per transplant and the time to first rejection was not different in patients with varicella compared to the other NAPRTCS patients. Five-year graft survival was not different for varicella cases when compared to other NAPRTCS patients with grafts surviving at least 6 months post-transplant. We conclude that the mortality rate of patients hospitalized with varicella in the first post-transplant year and the risk of subsequent graft dysfunction may be significantly lower than previously described. However, varicella remains a significant cause of potentially avoidable hospitalization in the first post-transplant year. Further study of the safety and efficacy of varicella vaccination in children with renal insufficiency and those post-transplant is warranted.

Adolescent↗
PubMed1997

Evaluation of neurotoxicity in pediatric renal transplant recipients treated with tacrolimus (FK506).

The presence of severe and mild neurotoxicity in our pediatric renal transplant recipients treated with tacrolimus was determined by chart review (severe neurotoxicity) and patient survey (mild neurotoxicity). 14 patients were studied (mean age 15 yr, 5 month, +/- 4.4 yr). 1 patient experienced seizures, felt to be related to malignant hypertension. No other episode of severe neurotoxicity was documented. Most patients (12/14) reported at least one mild neurologic symptom, and half stated their symptoms were present at least 'most of the time'. The most frequent complaints were myalgias (7/14, 50%) and tremors (7/14, 50%) followed by fatigue (5/14, 38%). Severe neurotoxicity may be relatively infrequent in pediatric renal transplant patients treated with tacrolimus. Milder neurologic complaints may be commonly seen in this population, but in general are not severe enough to cause discontinuation of tacrolimus.

Adolescent↗
PubMed1997

Antibody levels to diphtheria, tetanus, and rubella in infants vaccinated while on PD: a Study of the Pediatric Peritoneal Dialysis Study Consortium.

To determine whether infants who receive routine childhood immunizations while on chronic peritoneal dialysis (CPD) develop protective antibody levels/titers, we measured antibody levels/titers in infants vaccinated with diphtheria/tetanus/pertussis (DTP) and measles/mumps/rubella (MMR) while on CPD. Eight CPD patients (median age 19 months, range 9-39 months) had measurement of antibody to diphtheria and tetanus toxoids. Seven of the 8 (88%) had protective levels of IgG antibody to both toxoids. The single patient who did not have protective antibody to either diphtheria or tetanus had a low total serum IgG. However, 3 other patients who had low IgG had protective antibody levels. Serial measurements of antibody to tetanus and diphtheria were obtained in 3 of the 8 patients. All maintained protective levels to both diphtheria and tetanus toxoids for as long as 24 months postvaccination. Antibody to rubella was also measured in 5 CPD patients (median 29 months, range 19-39 months), and all had protective antibody titers despite the fact that 3 had low total serum levels. In conclusion, most but not all infants immunized while on CPD have protective antibody levels/titers to diphtherial, tetanus, rubella. Alteration of the routine schedule for immunizations does not appear to be necessary. However, periodic measurements of antibody may be indicated, particularly to live vial vaccines, prior to transplantation.

Antibodies, Bacterial↗
PubMed1996

Haemophilus influenzae type b immunization in infants on peritoneal dialysis. Pediatric Peritoneal Dialysis Study Consortium.

As part of a multi-center collaborative study, we measured antibody levels to Haemophilus influenzae type b (Hib) in ten chronic peritoneal dialysis (CPD) patients, aged 39 months or less, who were immunized while on CPD. Nine of the ten developed protective antibody levels to Hib. Four patients had serial measurements of antibody and all maintained protective levels, although the levels did decrease in two patients. Thus most, but not all, infants immunized with Hib vaccine while on CPD develop protective antibody levels. The factors responsible for vaccine failure are not clear. Whether patients maintain protective antibody over time needs to be determined.

Antibodies, Bacterial↗
PubMed1995

IgG subclass levels in pediatric patients on chronic peritoneal dialysis.

Patients maintained on chronic peritoneal dialysis (CPD) have been reported to have a variety of abnormalities of humoral immunity, including hypogammaglobulinemia, altered response to vaccination, and selective absence of IgG2. We measured serum immunoglobulin and IgG subclass levels in 22 pediatric CPD patients followed at our institution; 8 patients had low total IgG; 4 of these had low levels of IgG2 and 3 also had low IgG1, but IgG2 levels were detected in all patients. Thus, many pediatric CPD patients may have low IgG, and some may have low IgG1 and IgG2 as a reflection of low total IgG. However, we did not demonstrate a selective absence of IgG2 in these patients.

Adolescent↗
PubMed1995

Cytokine production by peripheral blood mononuclear cells from pediatric chronic peritoneal dialysis patients.

Previous reports have documented impaired cytokine production by peritoneal macrophages in chronic peritoneal dialysis (CPD) patients. To determine if this observed defect was a reflection of systemic mononuclear cell dysfunction, the function of peripheral blood mononuclear cells obtained from pediatric patients on CPD was assessed after stimulation with lipopolysaccharide (LPS). Levels of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) mRNA and protein were measured before and after stimulation with LPS. There was no significant difference in the response of mononuclear cells from CPD patients and normal controls in terms of increase in TNF-alpha mRNA [median stimulation index (SI) = 6.6 vs. 3.7, P = 0.35] or IL-1 beta mRNA (median SI = 6.2 vs. 6.5, P = 1.0). There was also no significant difference between the median increase in TNF-alpha protein secretion (median 372 pg/ml vs. 373 pg/ml, P = 0.60). These results suggest that systemic mononuclear cell function may be intact in CPD patients, and therefore this does not account for the dysfunction of peritoneal macrophages that has been previously reported.

Adolescent↗
PubMed1995

Renal proximal tubular epithelium from patients with nephropathic cystinosis: immortalized cell lines as in vitro model systems.

The renal proximal tubule is a major site of injury in a variety of congenital/metabolic diseases including nephropathic cystinosis, the most commonly known cause of renal Fanconi's syndrome. In this lysosomal storage disease there are defects in proximal tubule function within the first few months of life. While culture of renal tubular cells from the urine of these patients is possible, development of immortalized cell lines would insure large numbers of homogeneous cells for studies of renal epithelial cell morphology and pathophysiology in this disease. To develop immortalized cells, cystinotic and normal proximal tubular cells in culture were exposed to an immortalizing vector, containing pZiptsU19 with the temperature sensitive SV40 T-antigen allele tsA58U19 and a neomycin resistance gene, and neomycin-resistant tubular cells were selected for propagation. Ten clones from cystinotic patients have been developed and characterized. All clones express T-antigen at permissive temperature (33 degrees C). Immortalized cells have an epithelial morphology and grow to form confluent monolayers; doubling times vary from 31 to 86 hours. Cystinotic clones are keratin, MDR P-glycoprotein, and alpha-95 kD brush-border associated protein positive but Tamm-Horsfall protein negative by immunocytochemistry, as are normal proximal tubule cells immortalized with this vector. This is consistent with a proximal tubule origin of the cystinotic clones. The cystine content of the cystinotic cells is 70 to 160 times that of normal renal proximal tubular cells in culture, with most of the cystine sequestered in cell lysosomes, confirming that these cell lines express the storage defect.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Fractionation↗
PubMed1995

Immunizations in children on PD: current guidelines and recommendations.

Antibody responses to currently recommended immunizations in pediatric patients on chronic peritoneal dialysis (CPD) have been measured and the results have been variable. Although the incidence of vaccine-preventable disease in pediatric CPD patients is not known, it appears that protection from these diseases may be reduced. The explanation for the abnormal response to vaccines might include lower seroconversion rates in these patients, with lower antibody titers or levels. Also a rapid decline of antibody levels or titers may occur as a consequence of continuous peritoneal dialysis. Specific vaccines that may result in a less than optimal response in pediatric CPD patients include hepatitis B virus, hemophilus influenza type b, measles, mumps, rubella and pneumococcal vaccine. Patients who receive these immunizations should be monitored closely. Increased vaccine dosage, reinforced vaccination schedules, as well as concomitantly administered adjuvant immuno-modulators may play an important role in more effective vaccination of pediatric CPD patients. It is important that vaccine response be monitored in these patients by measuring specific antibody titers or levels to ensure adequate protection from vaccine-preventable illness.

Adolescent↗
PubMed1994

Neisseria sicca peritonitis in a patient maintained on chronic peritoneal dialysis.

Neisseria sicca, previously classified as a "nonpathogenic" organism, has now been recognized as a cause of many infections, including endocarditis and meningitis. However, it has not been reported as a cause of peritonitis. We present a case of documented N. sicca peritonitis immediately following an episode of Staphylococcus aureus peritonitis in a pediatric chronic peritoneal dialysis (CPD) patient. N. sicca should be considered as a possible pathogen in CPD-associated peritonitis.

Anti-Bacterial Agents↗
PubMed1993

Defective antibody response to Hemophilus influenzae type b immunization in children receiving peritoneal dialysis.

Pediatric end-stage renal disease patients, maintained on chronic peritoneal dialysis (CPD), may have a variety of immunological abnormalities, including hypogammaglobulinemia and poor responses to vaccines. We measured antibody levels to Hemophilus influenzae type b (Hib) in 24 CPD patients. Eight children received primary Hib immunization while undergoing CPD. Of these, 1 of 8 (12%) lacked protective levels of antibody. In another child, who had an initial protective response, antibody levels were undetectable 12 months after immunization. Sixteen of the patients had not been immunized with Hib vaccine because they were more than 5 years old when the vaccine was licensed. In this group, 5 of 16 (31%) lacked protective levels of anti-Hib antibody. Of those available for follow-up, 3 responded normally to Hib vaccine. It is not sufficient to provide childhood immunizations to CPD patients with the assumption that those immunizations will lead to long-lived immunity. Antibody levels should be measured within a month of immunization and at regular intervals thereafter to document immunity.

Adolescent↗
PubMed1993

Hypogammaglobulinemia and fatal sepsis in an infant maintained on peritoneal dialysis.

Chronic peritoneal dialysis (CPD) is a common form of renal replacement therapy in children. Recent studies suggest that immunological abnormalities, in particular hypogammaglobulinemia, may develop in children and infants on peritoneal dialysis. We report an infant maintained on CPD who died of gram-negative sepsis. At post-mortem examination, he was noted to have severe panhypogammaglobulinemia.

Agammaglobulinemia↗
PubMed1992

Cyclosporine in the treatment of azathioprine-induced red cell aplasia following renal transplantation.

Azathioprine, a well-known immunosuppressive agent, is used extensively in renal transplantation. There have been several case reports of pure red cell aplasia induced by this drug following a successful kidney transplant. Previous management of azathioprine-induced red cell aplasia included reduction of azathioprine dose, or treatment with cyclophosphamide. We propose the substitution of cyclosporine for azathioprine, in this clinical setting. Not only does cyclosporine allow recovery of bone marrow function, but it maintains a level of immunosuppression which stabilizes renal function in the post-transplant patient.

Adult↗
PubMed1992

Accelerated growth rates in children treated with growth hormone after renal transplantation.

To determine the usefulness of growth hormone treatment among children with renal allografts, we treated nine children with functioning renal transplants who were less than 16 years of age and had poor growth. The nine children, who were aged 12.6 +/- 4.0 years, had (1) heights greater than 2.5 SD less than the mean for age, (2) growth rates less than or equal to 5 cm/yr, and (3) additional growth potential, as assessed by bone age (8.9 +/- 2.8 year). Insulin-like growth factor I, thyrotropin, and thyroid hormone levels were normal for age in all children. Growth hormone treatment increased growth rates from 1.9 +/- 1.1 cm/yr to 7.2 +/- 1.8 cm/yr without accelerating skeletal maturation and without advancing pubertal status. During growth hormone treatment, serum creatinine concentration rose from 140 +/- 50 to 190 +/- 80 mumol/L (1.6 +/- 0.6 to 2.1 +/- 0.9 mg/dl) (p less than 0.05), and creatinine clearances decreased from 0.79 +/- 0.37 to 0.58 +/- 0.30 ml/sec per 1.73 m2 (47 +/- 22 to 35 +/- 18 ml/min per 1.73 m2) (p less than 0.05) but then remained stable. Growth rates of two patients returned to pretreatment rates when growth hormone treatment was discontinued after 5 and 7 months because of increased serum creatinine values. Growth hormone treatment may be useful as adjunctive therapy for increasing growth rates in selected children with renal allografts who have poor growth; however, serum creatinine concentrations should be closely monitored during such treatment.

Adolescent↗
PubMed1992

Acute tubular necrosis associated with Lowe's syndrome: possible role of rhabdomyolysis.

The oculo-cerebral-renal syndrome of Lowe is an X-linked recessive disorder characterized by severe mental retardation, congenital cataracts, renal tubular dysfunction, growth retardation, hypotonia, glaucoma, and rickets. Recently, it has been found that serum concentrations of the muscle enzymes are elevated, providing evidence that there is primary muscle involvement in this disorder. The renal functional abnormalities that occur have also been further delineated. Renal tubular dysfunction presents within the first year of life, followed by a serum creatinine level that increases with age. Renal failure generally occurs in the fourth decade of life. We report two patients with Lowe's syndrome who presented with new onset of acute renal failure (ARF). Workup of their ARF established the diagnosis of acute tubular necrosis with evidence of rhabdomyolysis in one case. These patients were treated aggressively with dialysis and had subsequent recovery of renal function to their baseline state. We suggest that patients with Lowe's syndrome who present with an acute change in their renal function should be treated early with vigorous hydration therapy. If dialysis is indicated, it should be initiated. Furthermore, these patients should be promptly evaluated for evidence of rhabdomyolysis with alkalinization of the urine if possible.

Biopsy↗
PubMed1991

Glucose tolerance in children with renal allografts and effect of growth hormone treatment.

We performed oral glucose tolerance tests (oGTTs) on 15 children who had functioning renal allografts received greater than or equal to 18 months previously, had adequate renal function, and had heights greater than 2.5 SD below the mean height for age. Three of the children had impaired glucose tolerance; their mean glucose levels during the last 2 hours of the oGTT were higher (p less than 0.05) than published control values. Integrated glucose concentrations correlated inversely with the prednisone dose on the first day of an alternate-day dosage schedule (R2 = 0.383) and directly with adiposity (partial R2 = 0.322). The integrated insulin concentration correlated directly with the prednisone dose on day 1 of an alternate-day regimen (R2 = 0.355) and with age (partial R2 = 0.163). In 10 children with renal transplants who had been treated with growth hormone for greater than or equal to 6 months, the mean fasting glucose concentration, integrated glucose concentration, and integrated insulin concentration during the oGTTs obtained after 6 months or 12 months of growth hormone treatment were not significantly different (p greater than 0.05) from values measured before the treatment. We conclude that increased integrated concentrations of both glucose and insulin during oGTTs in children with renal allografts correlate with the dose of prednisone administered on the first day of an alternate-day schedule, with age, and with adiposity index. Growth hormone treatment of children with renal allografts who are growing poorly does not significantly affect glucose metabolism as assessed by oGTT.

Adolescent↗
PubMed1991

Culture of renal tubular cells from the urine of patients with nephropathic cystinosis.

Nephropathic cystinosis represents a prototype for lysosomal storage diseases and is the most common cause of renal tubular Fanconi's syndrome. Mechanisms of the tubular transport defects in this disease have not been defined, however, in part because the cells readily cultured from affected patients, leukocytes and fibroblasts, do not express epithelial transport functions. Except for a single autopsy report, renal tubular cells from these patients have not been studied in vitro. In these studies, noninvasive harvesting and culture of renal tubular cells from the urine of patients with cystinosis is described. Cultures of renal tubular cells could be established from over 50% of the isolates which contained viable cells and which remained uncontaminated in vitro. Cells had an epithelial morphology in culture, and the majority of cultured cells expressed proximal tubular brush border marker enzyme. Cultured cells also expressed the storage defect in vitro, containing cystine levels up to 100 times those of normal cells. Cultured cells could be depleted of cystine by using the thiol cysteamine. This in vitro model system should be very useful for studying the mechanisms of renal tubular transport defects in this disease.

Cells, Cultured↗
PubMed1991

Dissociation of tubular cell detachment and tubular cell death in clinical and experimental "acute tubular necrosis".

"Acute tubular necrosis" in humans is often characterized histologically by tubular cell loss and nonreplacement rather than by frank cellular necrosis. It has been assumed that tubular cells detach from the tubular basement membrane after the occurrence of irreversible cell injury and/or cell death. We examined voided urine from patients with native kidney and transplant kidney "acute tubular necrosis" and found significant tubular cell shedding with up to 100% viability of voided tubular cells, as determined by exclusion of trypan blue. Histochemical stains for the brush border enzyme gamma-glutamyl transpeptidase and electron microscopy of cell isolates demonstrated that 30 to 100% of the voided cells were of proximal tubule origin. Moreover, epithelial cell cultures were readily established from noncontaminated voided specimens, and more than 80% of the cells in monolayers expressed gamma-glutamyl transpeptidase activity in vitro. Electron microscopy of cell monolayers confirmed proximal tubular differentiation in the majority of cells in the monolayer, with the remainder having an appearance more consistent with distal origin. In rabbit models of acute ischemic (pedicle clamp) and toxic (HgCl2 and glycerol-induced) injury, tubular cell shedding was also significant, with a mean of 25 to 30% of the voided cells viable. Epithelial cells were successfully cultured and passed from animals with ischemic renal injury. In vitro studies were carried out in cultured human proximal tubular cells to assess suitability of this system for more direct study of the phenomenon of cell detachment in response to injury. We found significant changes in cell shape in response to exposure to anoxia and HgCl2 in these cultures, with extensive cell rounding and retraction at times when cell viability remained high. This in vitro system could prove useful for defining mechanisms of renal tubular cell detachment in response to injury and for examining potential interventions to prevent epithelial disruption and loss of functional integrity. These strategies may ultimately have clinical relevance in patients with "acute tubular necrosis".

Acute Kidney Injury↗