Averaging of strongly varying signals.

Forces acting at the hip joint during a given activity often vary much between trials and subjects. Large variations are also encountered in many other biomechanical signals. Arithmetic mean curves then lead to falsified results, especially if extreme values occur at very different times. A method was developed for calculating a typical curve from such varying, time dependent signals. All cycle times are first averaged and the signals are then more and more smoothed using Fourier series with decreasing numbers of harmonics. The remaining extrema are analysed to decide whether they are typical for all curves or not. This is done by systematically cutting off a varying number of extrema at the beginning or end of all curves. After this an equal number of extrema remains in all curves. These extrema are then shifted to average positions in time, i.e. the times between consecutive extrema are compressed or expanded, and the standard deviation of all curves is calculated. The combination of cut off extrema which results in the smallest standard deviation is then used further on. The same time distortions are applied to the original curves and their arithmetic mean finally results in the typical signal. This procedure is well suited for averaging hip contact forces and other varying signals as long as their complexity and variation is not extremely large.

Epstein-Barr virus in pediatric patients after renal transplantation.

BACKGROUND: Pediatric allograft recipients are at an increased risk for lymphotropic virus-associated disorders, particularly in association with primary EBV infection. PATIENTS AND METHODS: Twenty-nine children, adolescents and young adults after renal transplantation were studied in comparison with a healthy young adult control group for evidence of primary, reactivated or chronic active EBV infection at two different time points. RESULTS: Prevalence of antibodies against viral capsid antigen (VCA) was > or = 90% in both groups, whereas anti-Epstein-Barr nuclear antigen (EBNA) was detected only in 19 of 26 seropositive patients compared with seropositive controls (p = 0.01). Persistence of EBV DNA in leukocytes for > or = 6 months was observed in 11 seropositive patients (38%) and one control patient (p < 0.007) using nested polymerase chain reaction. In the transplant recipients, 3 cases of primary EBV infection and 3 cases of chronic active EBV infection were identified. One of these cases developed a non-Hodgkin lymphoma one year later. CONCLUSION: The results suggest that determination of pretransplant antibody status in recipients, rapid detection of EBV infection in seronegative symptomatic recipients, and regular screening for persistent EBV DNA in patients at risk to develop post-transplantation lymphoproliferative disease should be performed.

Dominant T cells in idiopathic nephrotic syndrome of childhood.

BACKGROUND: Because of several studies, idiopathic nephrotic syndrome (INS) of childhood is suspected to have an immunologic pathogenesis with T cells playing a major role. To investigate this hypothesis further, we studied the diversity of the CDR3 region of the T-cell receptor (TCR) beta-chain from peripheral T cells isolated from patients with INS. METHODS: The study was performed over a three-year period to obtain longitudinal data on the repertoire of peripheral T cells. mRNA from peripheral mononuclear cells (PBMCs) of seven INS patients and two healthy controls (NHD) was prepared and analyzed for CDR3 length polymorphism of TCR beta-chain by spectratyping. RESULTS: All INS patients presented individually skewed spectratype histograms in at least one Vbeta-family. Patients suffering from a frequent relapsing course of INS or a focal global sclerosis showed some alterations to persist in all samples isolated in the observation period (up to 3 years). In addition, sequence analyses of the beta-chain of the TCR CDR3 region confirmed clonal expansion of peripheral T cells in those patients who had displayed spectratype alterations. CONCLUSIONS: The data give strong evidence for an direct involvement of CD8+ T cells in the complicated course of INS.

Clinical outcome of Schönlein-Henoch purpura nephritis in children.

We studied the long-term outcome of 64 children with biopsy-proven Schönlein-Henoch purpura (SHP) nephritis over 1-23 years of follow-up. Overall renal survival 10 years after onset was 73%. Multivariate logistic regression analysis identified initial renal insufficiency (P=0.004), nephrotic syndrome (P=0.037), and the severity of histological alterations, as defined by the proportion of glomerular crescents (P=0.051), as significant independent predictors of progressive renal failure. Four patients followed for more than 19 years showed glomerular damage after transient recovery. Eight children with crescentic nephritis associated with a rapidly progressive course and/or persistent nephrotic syndrome were treated by at least seven sessions of plasma exchange (PE) within 16 weeks of onset of purpura. During treatment serum creatinine levels dropped in each patient from a mean of 2.3 to 1.1 mg/dl, followed by a rebound increase. Repeated courses of PE in 5 patients produced comparable responses. Four patients undergoing PE reached end-stage renal disease at 1.2.-3.7 years after onset, whilst 3 finally were in preterminal renal failure (creatinine 3.2-6.1 mg/dl after 7-13.5 years), and 1 patient reached a normal glomerular filtration rate. Our experience suggests that initial renal insufficiency is the best single predictor of the further clinical course in children with SHP nephritis. Early PE appears to delay the progression in some patients with severe, rapidly progressive forms of the disease.

Inverted ratio of m-fas/s-fas expression in early onset pauciarticular juvenile chronic arthritis.

The expression of m-fas/apo1 (CD95) and its soluble form (s-fas) was studied in patients with early onset pauciarticular (n = 23) and systemic juvenile chronic arthritis (n = 7). RNA was prepared from peripheral blood of patients and 22 healthy controls and from 23 samples derived from the synovial fluid of JCA patients. The ratio of m-fas/s-fas transcripts was calculated by densitometry of fas-specific RT-PCR products. An inverted ratio of m-fas/s-fas transcripts was found in PBMC and mononuclear cells from the joints of early onset pauciarticular JCA patients. The m-fas/s-fas ratios were similar in PBMC and mononuclear cells from synovial fluid. PBMC from patients with a systemic JCA showed the same m-fas/s-fas ratio as healthy controls, with an inverted ratio of both transcripts in cells from the synovial fluid. The data indicate a role of Fas/Apo1 regulated apoptosis in EOPA-JCA which is not limited to the affected joints.

Primary hyperoxaluria 1: catch up growth and normalization of oxaluria 6 years after hepatorenal transplantation in a prepubertal boy.

We present data on urinary oxalate (U(OX)), renal function, growth and bone age in a 10-year-old male with primary hyperoxaluria type 1. The patient had undergone combined liver-kidney transplantation at the age of 4.5 years. UOX increased up to 10(4) micromol/24 h after transplantation and declined to normal values thereafter. Excessive Uox concentrations after surgery might have been due to a bone pool of unsoluble oxalate and declined spontaneously. Creatinine clearance remained stable during observation period. The boy showed significant catch up growth. Height standard deviation score for chronological age improved from -2.4 before transplantation to -0.3 after 6 years. Radiological bone density improved at the same time. Hepatorenal transplantation should be performed in children with primary hyperoxaluria 1 before end-stage renal failure to normalize oxalate excretion and improve growth and bone mineralization.

Biocompatibility testing of a new silver-impregnated catheter in vivo.

The purpose of this investigation was to compare the local effects of polyurethane (Tecothane) and silicone tubes with or without silver impregnation in rats. Bacterial colonization or infection of the exit site and/or tunnel were documented and interpreted. All tubes were placed subcutaneously or percutaneously in the neck of 41 Sprague-Dawley rats and guided beneath the dorsal muscles into the peritoneal cavity. The incidence of bacterial abscesses along the implanted tubes was evaluated daily. After 90 days, or earlier if sepsis developed, the animals were killed painlessly and various organs and tissues from the entry site and the catheter tunnel examined histologically. In the group where polyurethane tubes were placed percutaneously, there was no difference in the frequency of abscesses between silver-impregnated and non-impregnated tubes (5/6 with and 5/7 without silver). The only difference noted was in the group with percutaneously placed silicone tubes between those with and without silver. Abscesses only occurred in 2/4 animals in the silver group and in 5/5 animals in the control group. Histological examination showed no difference in either group between infectious and foreign body reactions. Silver particles in subcutaneous, muscle and peritoneal tissue could not be demonstrated.

A comparative study of impact dynamics: wobbling mass model versus rigid body models.

We demonstrate that the results of inverse dynamics depend sensitively on the model used to simulate the human body. For this reason we produce "ideal" input data of the ground reaction force and the heel acceleration for a computer simulated drop jump with a wobbling mass model. Then we determine the internal torques and forces in the knee and hip joint via inverse dynamics by employing a rigid body model. It turns out that during the impact phase the analysis with the rigid body model yields completely incorrect internal torques and forces.

Successful percutaneous transluminal angioplasty for treatment of renovascular hypertension in a 15-month-old child.

UNLABELLED: In young children with renal artery stenosis the applicability of percutaneous transluminal angioplasty is limited by the small vessel size. We report our experience in a 15-month-old girl with severe hypertension, who underwent successful balloon dilatation of a tight renal artery stenosis caused by fibromuscular dysplasia. The procedure was performed using the guided co-axial balloon catheter technique with a 6 F right coronary Judkins catheter, a 0.014" guidewire and a 2 mm coronary artery balloon dilatation catheter. Antihypertensive medication was discontinued 6 weeks after the procedure. During a follow up period of 11 months, Doppler sonography revealed no evidence of recurrent renal artery stenosis. CONCLUSION: Percutaneous transluminal angioplasty of renal artery stenosis can be performed safely in young children using equipment originally designed for treatment of coronary artery stenosis in adults.

[Azathioprine ingestion with suicidal intent by an adolescent with chronic juvenile polyarthritis]. / Azathioprin-Ingestion in suizidaler Absicht bei einem Jugendlichen mit juveniler chronischer Polyarthritis.

We report on a 13 years 7 months old boy who ingested 650 mg azathioprine in a suicide attempt. His baseline medication was azathioprine and methotrexate for control of juvenile chronic polyarthritis. After the induction of vomiting by ipecacuanha sirup and administration of charcoal (1 g/kg), he was closely followed for haematological, hepatic, and renal side effects. During the following days, no serious adverse events were noted except that the thrombocyte (from 403,000 down to 199,000/microliter) and total leukocyte count decreased moderately (from 12,000 down to 7100/microliter). On the basis of this case report and the available literature, the potential acute toxicity of azathioprine and possible treatment modalities are discussed.

Continuous plasma resin perfusion for detoxification of methotrexate.

UNLABELLED: Acute renal failure is a rare but very severe side-effect of methotrexate (MTX) treatment requiring extracorporeal detoxification. A new detoxification regime, consisting of a haemodiafiltration (HDF) and continuous plasma resin perfusion (PRP) over anion exchange resin column with high affinity for MTX, was used for treatment of MTX-induced acute renal failure in a 2-year-old boy with medulloblastoma. More than 99% of MTX was removed from plasma by perfusion over the resin column resulting in a marked decrease of MTX plasma half-life. No haematological complications occurred. CONCLUSION: The use of PRP alone or in combination with HDF is a new and effective treatment strategy for extracorporeal detoxification of MTX.

Successful systemic low-dose lysis of a caval thrombus by rt-PA in a neonate with congenital nephrotic syndrome.

PURPOSE: Thrombotic complications in nephrotic syndrome due to renal loss of antithrombin III (AT III) are well known. With this case report, we want to demonstrate the possibility of achieving the lysis of such a thrombosis in the neonatal period with low-dose rt-PA. PATIENTS AND METHODS: We treated a 10-day-old newborn who had congenital nephrotic syndrome, who developed a caval thrombosis during the first days of his life. After a trial of heparin (up to 20 IU/kg/hour) over a period of 24 hours and treatment with AT III (2 x 250 IU/day) proved to be ineffective, we started systemic thrombolytic therapy with rt-PA. An initial bolus of 0.4 mg/kg during 1 hour was followed by an infusion of 0.5 mg/kg/d rt-PA over a period of 36 hours. Low-dose heparin (5 IU/kg/hour) was given simultaneously. Complete clot dissolution could be achieved this way. No adverse effects were observed, including no clinical signs of bleeding. CONCLUSION: It seems that low-dose rt-PA treatment is safe and effective in dissoluting large caval thromboses in neonates.

Proteinuria and other renal functions in Wilson's disease.

Renal lesions have repeatedly been described in Wilson's disease (WD). We investigated the excretion of total protein, albumin, low (LMW) and high molecular weight (HMW) proteins, N-acetyl-beta-D-glucosaminidase (NAG), and calcium, as well as creatinine clearance, in 24-h urine samples of 41 patients with WD aged 6-37 (mean 17) years who had been treated for a period of 0-15 (mean 4.5) years with D-penicillamine (900 mg/day). The amount of all protein excreted was significantly increased compared with controls, 39% of patients presenting with total proteinuria more than two standard deviations from the mean of controls. The changes in protein excretion depended on the duration of treatment. LMW proteinuria was elevated almost exclusively in the first 2 years after the start of treatment, indicating early tubular damage. This is supported by an initially high excretion of beta 2-microglobulin, NAG, and calcium. Increased excretion of HMW proteins, including albumin, persisted over longer periods, which suggests glomerular injury in some patients, possibly related to the use of D-penicillamine. Creatinine clearance remained roughly within normal limits. We propose that renal function should regularly be checked in patients with WD.

Prospective evaluation of pretransplant blood transfusions in cadaver kidney recipients.

BACKGROUND: A beneficial effect of pretransplant transfusions on graft survival was demonstrated in the early 1970s. In the mid-1980s, however, retrospective studies showed that transfusions had lost their graft-protective effect in the cyclosporine era. During the last 10 years, deliberate transfusion pretreatment of transplant patients has been discontinued. METHODS: Within a collaborative project of 14 transplant centers, prospective recipients of cadaver kidney grafts were randomized to receive either three pretransplant transfusions or transplants without transfusions. RESULTS; The graft survival rate was significantly higher in the 205 transfusion recipients than in the 218 patients who did not receive transfusions (at 1 year: 90+/-2% vs. 82+/-3%, P=0.020; at 5 years: 79+/-3% vs. 70+/-4%, P=0.025). Cox regression analysis showed that this effect was independent of age, gender, underlying disease, prophylaxis with antilymphocyte antibodies, and preformed lymphocytotoxins. CONCLUSIONS; Transfusion pretreatment improves the outcome of cadaver kidney transplants even with the use of modern immunosuppressive regimens.

Outbreak of Escherichia coli O157:H7 infection in a large family.

An outbreak of bloody and nonbloody diarrhoea caused by Escherichia coli O157:H7 including one case of haemolytic uraemic syndrome (HUS) and two cases of haemolytic anaemia, in five siblings (aged 2.5 to 11.3 years) and their playmate was investigated. Using sorbitol-MacConkey agar, colony blot hybridisation, and immunomagnetic separation, Shiga toxin 2-producing Escherichia coli O157:H7 was isolated from all children but the HUS patient; however, this patient had high immunoglobulin M antibody titres against Escherichia coli O157 lipopolysaccharide. Escherichia coli O157 isolates from all patients were indistinguishable in serotype, virulence properties, and genomic background, indicating that the same strain caused the infections. These data confirm the importance of person-to-person transmission.

HLA-DR7 predicts the response to alkylating agents in steroid-sensitive nephrotic syndrome.

There is a lack of reliable predictors of the response to alkylating agents in children with idiopathic nephrotic syndrome (NS). HLA-DR7 is strongly associated with the frequency of relapses in steroid-sensitive NS before cytostatic therapy. We therefore examined retrospectively the time to the first relapse and the incidence of subsequent relapses in 54 HLA-typed children with frequently relapsing NS, after treatment with cyclophosphamide (n = 49) or chlorambucil (n = 5) for 8 or 12 weeks; 38 patients were HLA-DR7 positive and 16 negative with 80% in both groups being steroid dependent. HLA typing was performed using serological or DNA typing methods. Renal biopsy showed minimal glomerular changes. A lower proportion of HLA-DR7 positive than negative patients remained in remission after 3 years (36% vs. 81%, P < 0.02) and 5 years (36% vs. 72%, P < 0.03). In the first 3 years after cytostatic therapy the mean number of prednisone-treated relapses was 1.3/patient per year in HLA-DR7-positive patients compared with 0.4 in negative patients (P < 0.025). There was no statistically significant difference in the proportion of relapse-free patients with and without steroid dependency. The HLA status predicts the response of NS patients to alkylating agents better than the rate of previous relapses.