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Biomedical subjects

E D Wolff

Publications and source records attributed to E D Wolff.

At least 19 recordsLinked to original sources

Pediatric renal transplantation in the Netherlands.

In the Netherlands, pediatric kidney transplantation programs are available in four centers. We retrospectively analyzed the results obtained over the past decade. Between 1985 and 1995, 231 patients (139 boys) received 269 transplants, including 61 repeat. The recipients were aged 1.9-21.8 yrs (mean 10.9), the donors 0.3-63.3 yrs (median 11.4, mean 19.7). Immunosuppression consisted of corticosteroids, cyclosporin A and azathioprine, in various combinations and dosages. The patient survival during follow-up was 97%. The overall graft survival was 73% at 1 yr and 60% at 5 yrs after transplantation. Major causes of graft loss were acute rejection (21%), thrombosis (12%) and chronic rejection (28%). Acute rejection episodes were noted in 74% of all grafts. First acute rejection episodes had a moderate predictive value for graft loss (relative risk (RR), compared to rejection-free grafts, 5.9). First rejection episodes occurring later than 3 months after transplantation were considerably more predictive (RR 18.3) than early ones. Grafts from living related donors (n = 35) yielded a superior 5-yr graft survival (77%) and remained free of rejection more often than grafts from adult cadaveric donors(43% vs. 25%). The results of pre-emptive transplants were excellent (n = 13, 5-yr survival 100%). Repeat transplants had the same results as primary transplants. Recipients younger than 4 yrs showed a poor 5-yr graft survival of 38% (n = 13). Single kidney grafts from donors younger than 4 yrs (n = 35) had a 5-yr graft survival of 44%. In contrast, kidneys from these young donors did well if transplanted en bloc (n = 10, 5-yr graft survival 89%). These overall results are in line with those of others. The results may be improved by expansion of immunosuppressive therapy in the first year and by thrombosis prophylaxis in high-risk patient-donor combinations. Better results may be expected from more extensive use of living related donations, pre-emptive transplantation and en bloc transplantation instead of single kidneys of young donors.

Adolescent↗

Primary hyperoxaluria type I: renal ultrasound before and after treatment.

Three patients with primary hyperoxaluria type I received therapy consisting of vitamin B6, magnesium oxide, and high oral fluid intake. Sonographic follow-up showed a variable response to treatment, ranging from normalization of renal tissue to no change at all. However, there is evidence of a correlation between laboratory findings and ultrasound findings during treatment.

Child↗

Intracellular amino acid concentrations in children with chronic renal insufficiency.

We studied amino acid concentrations in granulocytes and plasma of 24 children with chronic renal failure and 15 healthy children. Granulocytes were isolated from 10 ml of blood using a dextran-Ficoll-Hypaque procedure. Intracellular levels of leucine, isoleucine, methionine, phenylalanine, lysine, histidine, tyrosine, and arginine were significantly lower in children with chronic renal failure than healthy children. There were no significant differences in intracellular and plasma amino acid concentrations between children with chronic renal failure on a well-balanced protein-restricted diet and children with chronic renal failure with a normal protein intake.

Adolescent↗

Verocytotoxin-producing Escherichia coli infection in hemolytic uremic syndrome in part of western Europe.

UNLABELLED: From September 1989 until September 1993, stool specimens and sera from 113 children with diarrhoea-associated haemolytic uraemic syndrome (HUS) from the Netherlands, two university hospitals in Belgium and one university hospital in Germany were examined for the presence of verocytotoxin-producing Escherichia coli (VTEC) infection. Evidence for VTEC infection was observed in 88 (78%) patients with HUS compared to 2 (3%) of the 65 children with acute gastro-enteritis Serotype O157 was the causative agent in 76 (86%) of these 88 patients with VTEC-associated HUS and verocytotoxin-2 (VT-2) was the most frequent toxin produced. Serological testing for antibodies to O157 O-antigen yielded the highest number of positive results compared to the other test methods. Antibodies to O157 were found in sera of 71 (65%) of 110 patients with HUS and one control serum. Stool and sera examination for VTEC in 95 family contacts of 28 patients with HUS demonstrated an evidence for VTEC infection 33 (35%). In contrast, in patients with HUS serological antibodies to O157 O-antigen were found in only 3 (4%) of 85 family contacts. CONCLUSION: In this part of Western Europe, VT2-producing Escherichia coli, mainly those belonging to serogroup O157, are the major cause of HUS in childhood.

Bacterial Toxins↗

A placebo-controlled, double-blind trial of growth hormone treatment in prepubertal children after renal transplant.

Sustained growth retardation in spite of a successful renal transplantation (RTx) is a serious problem for many pediatric allograft recipients. Biosynthetic growth hormone (GH) was given to 11 prepubertal children with severe growth retardation after RTx in a placebo-controlled double-blind study, assessing its effect on height velocity (HV), bone maturation, renal function, plasma IGF-I and IGF-II, serum IGF-binding proteins (IGFBP), and lipid and carbohydrate metabolism. Six months of GH (4 IU/m2/day s.c.) was either preceded or followed by six months of placebo. The patients underwent a full examination every three months. All children completed the study. Mean HV improved significantly with GH therapy (P < 0.0001), but there was also some improvement with placebo (P = 0.06). The GH-induced HV increment exceeded that of placebo by 2.9 cm/six months. Bone maturation was not accelerated. Acute renal graft rejection did not occur in any of the patients. 125I-thalamate and 131I-hippuran tests showed that mean glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) did not change significantly during GH therapy. GH caused a significant increase in IGF-I (P < 0.0001), which was far greater than the insignificant increase in serum IGFBP-3 levels (P = 0.16). Mean serum levels of total cholesterol, low density lipoprotein, apolipoprotein-A1 and -B, which are elevated at the start of the study compared with that of controls, did not change significantly during GH therapy. GH induced a significant increase in mean integrated plasma insulin levels during oral glucose tolerance test, without changing plasma glucose levels. Serum fructosamine and parathyroid hormone levels remained constant. Impressive HV increment can be achieved with GH therapy in children with growth retardation after RTx, without significant changes in renal function. Bone maturation appears unaffected, suggesting an improve final height.

Adolescent↗

Four cases of hemolytic uremic syndrome--source contaminated swimming water?

In June '93, 4 children, aged 1.5-3.5 years, all living in one town, were admitted to our hospital with the diagnosis hemolytic uremic syndrome (HUS) within one week. In cooperation with the local health authorities a common source was searched for. Questionnaires indicated that the single condition shared by all patients was swimming water. The patients were not acquainted, visited different daycares, and had no food resources in common. All 4 patients bathed in the same, shallow, recreational lake within a period of 5 days. During this time the air temperature was high according to Dutch standards (around 27 degrees C), and many people visited the lake, estimated several hundreds a day. The water level was lower than normal. Diarrhea followed 3-11 days after swimming and the first clinical symptoms of HUS developed 6-7 days after the onset of diarrhea. The lake was closed for swimming when the fourth HUS patient was diagnosed and the possibility of transmission by way of the lake was mentioned. E. coli O157: H7 was demonstrated in the fecal samples of 2 index patients. The samples were taken 9-20 days after the start of diarrhea. Antibodies to O157 and verotoxin 2 were strongly positive in all patients. A local outbreak of diarrheal illness was not registered. Of 16 family members who also swam in the same lake, 7 developed symptoms of enteritis, 3 had positive cultures of their fecal samples and 5 had positive serology. Pulsed-field gel electrophoresis of the E. coli isolates of the patients and family members showed an identical pattern. No O157: H7-DNA could be detected in filter concentrated lake water samples using polymerase chain reaction (PCR) enhancement. These samples were, however, taken 16 days after the latest possible date of contamination of our patients, 15 days after decrease of the air temperature to 15-17 degrees C, and 14 days after the inlet from water from the environment. It could thus very well be that the microorganism was no longer present. This third report of swimming water associated HUS should direct environmental surveys in similar cases of local HUS outbreaks.

Antibodies, Bacterial↗

Use of recombinant human growth hormone (rhGH) in pubertal patients with CRI/dialysis/post-transplant: Dutch data. Dutch Study Group on Growth in Children with Chronic Renal Disease.

In the intermediate term, recombinant human growth hormone (rhGH) therapy in a dose of 28-30 i.u./m2/week accelerates growth significantly in most pubertal patients with growth retardation secondary to chronic renal insufficiency (CRI), dialysis and after renal transplantation (RTx), without evidence of adverse effects or acceleration of bone maturation. Therefore, rhGH therapy may well improve the final height of these patients.

Adolescent↗

Whole mouth microbiota effects following subgingival delivery of sanguinarium.

An increased incidence of antibiotic-resistant bacteria and yeast overgrowth has been reported following various periodontal treatments. The objective of this study was to detect possible overgrowth of opportunistic bacteria and fungi as well as changes in normal microbiota after application of a biodegradable delivery system containing 5% sanguinarium (ABDS-S) to one quadrant in a split-mouth study. An oral hygiene quadrant served as a control. The ABDS-S treated and control periodontal sites as well as the saliva of 17 subjects were sampled prior to treatment, immediately after ABDS-S removal at 7 days, and again at 30 and 60 days. At Day 7 sanguinarium-resistant bacteria increased in both control and ABDS-S periodontal sites as well as in the saliva. Enteric Gram-negative bacilli in both control and ABDS-S periodontal sites were 2.2 to 3.4 log colony forming units higher at Day 7 compared to baseline. This overgrowth was transient in that levels became undetectable at Days 30 and 60. No such overgrowth was observed for C. albicans or other fungi, or for S. aureus or other staphylococci in any periodontal sites. Levels of Actinomyces increased at Days 30 and 60 in both control and ABDS-S sites as well as saliva. These changes strongly suggest that a 7 day ABDS-S treatment in one quadrant of the mouth led to significant microbiota changes in the treated and control quadrants as well as in the saliva. Future microbial studies involving antimicrobials delivered by local delivery systems must consider the crossover effects of treatment inherent in the split-mouth design.

Adult↗

Growth hormone treatment in growth-retarded adolescents after renal transplant.

Growth failure is a psychosocial problem for many patients who have undergone renal transplantation. 18 adolescents (mean age 15.6, range 11.3-19.5) with severe growth retardation after renal transplantation were treated with biosynthetic growth hormone (GH) for 2 years. All received prednisone, administered daily or on alternate days, with azathioprine and/or cyclosporin A. 16 were blindly assigned to one of two GH doses (4 vs 8 IU per m2 per day). Growth, bone maturation, renal graft function, plasma insulin-like growth factors, serum binding proteins, and other biochemical parameters were checked regularly. Glomerular filtration rate and effective renal plasma flow were tested with 125I-Thalamate and 131I-Hippuran. Data on growth and glomerular filtration rate during GH treatment were also compared with those of matched non-GH-treated controls. Mean (standard deviation) increment in height after 2 years of GH was 15.7 (5.1) cm, significantly greater (p < 0.0001) than in matched controls, 5.8 (3.4) cm. Results were similar for the two GH dosage groups. Bone maturation was not accelerated. Glomerular filtration rate and effective renal plasma flow did not change significantly. The incidence of a > 25% reduction in glomerular filtration rate over 2 years was not significantly higher in GH-treated patients than in non-GH-treated controls (39% vs 32%, p = 0.97). Although a few patients had deterioration of graft function, we could not find a relation with GH treatment. Our results show that sustained improvement of height can be achieved with GH in severely growth-retarded adolescents after renal transplantation.

Adolescent↗

Growth after renal transplantation in prepubertal children: impact of various treatment modalities.

A retrospective study evaluated posttransplant growth of 70 prepubertal children during the first 2 y after renal transplantation (RTx). Immunosuppressive treatment consisted of prednisone administered either daily or on alternate days in combination with either azathioprine or cyclosporin A. The increment in height standard deviation score for chronologic age during the first 2 y after RTx was less than 0.5 SD for 70% of the study population. The predictive factors for posttransplant growth were determined by evaluating several factors and treatment modalities singly and simultaneously in a multiple regression analysis. Patients with the most severe growth retardation at RTx appeared to have the most pronounced growth spurt after RTx, but even they never had complete catch-up growth, and 2 y after RTx they were still shorter than those with less severe growth retardation at RTx. Alternate-day instead of daily prednisone administration had a significantly positive influence, whereas a high cumulative dose of prednisone, azathioprine instead of cyclosporin A therapy, and a persistently reduced GFR (GFR < 50 mL/min/1.73 m2) had a significantly negative influence on catch-up growth during the 2 y after RTx. Other factors, such as gender, chronologic and bone age at RTx, primary renal disease, duration of initial dialysis, repeat RTx, and target height SD score for chronologic age, whether evaluated singly or simultaneously with other significant factors, appeared to have no significant influence on post-RTx growth. Thus, 70% of the prepubertal children do not experience appreciable catch-up growth during the first 2 y after RTx. Optimization of pretransplant height appears very important. Immunosuppressive treatment with cyclosporin therapy in combination with a minimal dose of alternate-day prednisone would then result in optimal post-transplant growth, particularly if the GFR remains above 50 mL/min/1.73 m2).

Azathioprine↗

Final height and its predictive factors after renal transplantation in childhood.

A retrospective study is reported assessing final height (FH) and its predictive factors in 52 patients (31 male, 21 female) who underwent renal transplantation (RTx) before the age of 15 y. They received prednisone daily or on alternate days as well as azathioprine. The study period covered 20 y. FH remained below the third height percentile [height standard deviation score for chronologic age (hSDSCA) < -1.88] for most of these patients (77% males, 71% females). Median (range) FH was 165.0 (143.0-176.8) cm in males and 153.0 (135.0-168.4) cm in females. Median difference between FH and target height was 15.0 and 15.4 cm for males and females, respectively. For both sexes, the median hSDSCA was already below -1.88 at the start of the first hemodialysis, after which it decreased significantly until the first RTx. After RTx, there was no significant improvement of hSDSCA. The predictive factors for FH were determined by evaluating various factors simultaneous in a multiple regression analysis. This analysis provided a regression equation for predicting FH. A higher hSDSCA at the time of the first RTx and alternate-day versus daily prednisone therapy both had a significantly positive influence on FH, whereas a longer duration of reduced GFR (< 50 mL/min/1.73 m2) had a significantly negative effect on FH. Other factors such as age or bone age at first RTx, primary renal disease, duration of initial dialysis, repeat RTx, and the cumulative dose of prednisone did not influence FH significantly. In conclusion, 71-77% of patients that received their first renal transplant before the age of 15 ended up with severely short adult stature. Optimization of the hSDSCA at first RTx appears very important. Long-term administration of prednisone on alternate days would then result in optimal FH, particularly if the GFR remains above 50 mL/min/1.73 m2.

Adolescent↗

Protein restriction in chronic renal failure.

The aim of the study was to investigate the effect of a protein restricted diet on renal function and growth of children with chronic renal failure. In a multicentre prospective study 56 children (aged 2-18 years) with chronic renal failure were randomly assigned to the protein restricted (0.8-1.1 g/kg/day) or the control group. All children were followed up by the same paediatrician and dietitian. After a follow up period of three years there was no significant difference in glomerular filtration rate between children on a protein restricted diet and children of the control group. There was no significant difference in weight with respect to height and height SD score between the protein restricted and the control group. Compliance with the protein restricted diet, as indicated by the prospective diet diaries and the serum urea:creatinine ratio, was good. This study shows that children with chronic renal failure do not benefit from a protein restricted diet.

Adolescent↗

Protein intake can not be estimated from urinary urea excretion.

We assessed the relationship between protein intake (calculated from a 3-day prospective dietary diary) and 24-h urinary urea excretion in 37 children with chronic renal failure. Protein intake was not restricted during the investigation period. The 24-h urinary urea excretion correlated poorly with the protein intake estimated from the dietary diary (r = 0.58). We conclude that although it is common practice to assess compliance with a protein-restricted diet in children with chronic renal failure with a dietary diary and 24-h urinary urea excretion, the value of this assessment is questionable.

Adolescent↗

Protein restriction affects fat intake and serum lipids in children with chronic renal failure.

Cardiovascular complications in patients with chronic renal failure have been associated with the hyperlipidemia present in many of these patients. Since a protein-restricted diet is often prescribed in an attempt to preserve renal function, we performed a randomized controlled study in children with chronic renal failure on the effect of a protein-restricted diet on fat intake and serum lipid profiles. Although total fat intake did not change, we found a lower cholesterol intake and a higher polyunsaturated/saturated fat ratio in the patients with the protein-restricted diet. This is probably caused by the restriction of animal protein which results in the replacement of animal fat by vegetable fat in the protein-restricted group. Moreover, we observed an increase of plasma cholesterol and low-density lipoprotein cholesterol in patients with a normal protein intake which was absent in the protein-restricted group. This suggests a favourable effect of the institution of a protein-restricted diet on lipid intake and plasma profile.

Adolescent↗

Placebo-controlled, double-blind, cross-over trial of growth hormone treatment in prepubertal children with chronic renal failure.

Stunted growth is a serious problem for children with chronic renal failure (CRF) despite normal endogenous growth hormone secretion and normal or elevated plasma concentrations of insulin-like growth factors (IGF) I and II. Biosynthetic growth hormone (GH) was given to 20 prepubertal children (eleven boys, nine girls; mean age 9.5 years, range 4-16) with CRF and severe growth retardation in a placebo-controlled, double-blind, cross-over trial. 6 months of subcutaneous injection of GH (4 IU/m2 per day) was either preceded or followed by 6 months of placebo injection. The patients had a full examination every 3 months. Sixteen children completed the study. Height velocity improved significantly with GH therapy (p less than 0.0001) and placebo (p less than 0.04), but the GH-induced height-velocity increase exceeded that of placebo by 2.9 cm per 6 months. There was a positive relationship between prestudy height velocity and height-velocity increase. Bone maturation was not affected. GH caused a significant increase in IGF-I and a moderate increase in IGF-II plasma concentrations. The pretreatment elevation of IGF-binding protein-1 decreased by almost 50% during GH therapy, while IGF-binding protein-3 increased significantly in concentration, although this increase was significantly smaller than the GH-induced increase in IGF-I. Fructosamine, lipid, and parathyroid concentrations remained constant. Renal function deterioration did not accelerate. Impressive height-velocity increase can be achieved with GH therapy in children with CRF and growth retardation without changes in renal function. Bone maturation appears unaffected suggesting improved final height. Treatment is best started before growth retardation becomes considerable.

Adolescent↗