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Biomedical subjects

U Querfeld

Publications and source records attributed to U Querfeld.

At least 19 recordsLinked to original sources

Uremia-related vascular calcification: more than apatite deposition.

In the present study, we characterized and compared the mineral phase deposited in the aortic wall of two different frequently used chronic renal failure rat models of vascular calcification. Vascular calcification was induced in rats by either a 4-week adenine treatment followed by a 10-week high-phosphate diet or 5/6 nephrectomy followed by 6 weeks of 0.25 microg/kg/day calcitriol treatment and a high-phosphate diet. Multi-element mapping for calcium and phosphate together with mineral identification was performed on several regions of aortic sections by means of synchrotron X-ray-mu-fluorescence and diffraction. Bulk calcium and magnesium content of the aorta was assessed using flame atomic absorption spectrometry. Based on the diffraction data the Von Kossa-positive precipitate in the aortic regions (N=38) could be classified into three groups: (1) amorphous precipitate (absence of any diffraction peak pattern, N=12); (2) apatite (N=16); (3) a combination of apatite and magnesium-containing whitlockite (N=10). The occurrence of these precipitates differed significantly between the two models. Furthermore, the combination of apatite and whitlockite was exclusively found in the calcitriol-treated animals. These data indicate that in adenine/phosphate-induced uremia-related vascular calcification, apatite is the main component of the mineral phase. The presence of magnesium-containing whitlockite found in addition to apatite in the vitamin D-treated rats, has to be seen in view of the well-known vitamin D-stimulated gastrointestinal absorption of magnesium.

Animals↗

Thoracic versus whole body bioimpedance measurements: the relation to hydration status and hypertension in peritoneal dialysis patients.

The whole body bioimpedance technique is a highly promising non-invasive, reproducible, fast and inexpensive bed-side method for monitoring hydration status. Using segmental bioimpedance measurements, it is possible to obtain information about the fluid change in each body segment (Song, Lee, Kim and Kim 1999 Perit. Dial. Int. 19 386-90). In this pilot study we have measured 25 male patients (30-65 yr, BMI 20-32 kg m(-2)) undergoing continuous ambulatory peritoneal dialysis (CAPD). Tetrapolar impedance measurements were obtained using the right-side technique (whole body), and a segmental impedance method focused in the thorax region. Blood pressure (BP) measurements were taken manually with a sphygmomanometer. Patients were classified as either stable (group 0) or unstable (group 1) using clinical parameters of overall cardiovascular risk. The Mahalanobis distance (dM2) was calculated for the mean blood pressure (BP(mean)), and the impedance parameter R normalized by body height H for the right-side (R(RS)/H) and the thorax segment (R(TH)/H). Differences between groups were significant (p < 0.0001) for R(TH)/H and for BP(mean), and less significant (p = 0.016) for R(RS)/H. Group 1 patients showed a small dM2 as compared with a reference patient (a critical patient with acute lung edema) with high BP(mean) and low values of R(TH)/H and R(RS)/H. Moreover, Group 0 patients showed a larger dM2 with respect to the reference patient, with lower BP(mean) and higher values of R(TH)/H and R(RS)/H. All patients classified as unstable by clinical assessment were correctly classified using R(TH)/H in conjunction with BP(mean) using dM2. Segmental-monofrequency non-invasive bioimpedance of the thoracic region could provide a simple, objective non-invasive method of support for facilitating the clinical assessment of CAPD patients.

Adult↗

[Kidney transplantation in childhood and adolescence].

The reasons for end-stage renal disease in pediatric patients differ from adults. The therapy of choice is renal transplantation. A total of 117 children and adolescents were treated with renal transplantation in 2003 in Germany. Immunosuppressive therapy and related comorbidities are the main problems in pediatric patients. The following article provides a summary of transplantation in children, preparation, and follow-up.

Adolescent↗

Severe parvovirus B19 encephalitis after renal transplantation.

Human parvovirus B19 is a common cause of benign erythema infectiosum (fifth disease) in otherwise healthy children. Immunocompromized patients are at risk of developing chronic infections leading to chronic hyporegenerative anemia. We report the case of a nine-year-old boy who presented five days after renal transplantation with seizures and signs of encephalitis on MRI. The clinical course was characterized by anemia and seroconversion for parvovirus B19 accompanied by a high viral load (>10(9) copies per milliliter). A transfusion of red blood cells that the patient required after transplantation was found to be negative for parvovirus B19, leaving the donated organ as the most likely source of infection. Reduction of the immunosuppressive regimen led to complete recovery of the patient with a stable RBC count upon discharge. Parvovirus B19 infections should be considered in the differential diagnosis of seizures after solid organ transplantation.

Anemia↗

Severe atherosclerosis of the aorta and development of peripheral T-cell lymphoma in an adolescent with angiolymphoid hyperplasia with eosinophilia.

We report an adolescent girl with a history of angiolymphoid hyperplasia with eosinophilia (ALHE) diagnosed at the age of 10 years. The patient also suffered from chronic persistent multiresistant herpes simplex virus infection. Atherosclerotic occlusive disease of the abdominal aorta and its major branches was observed at the age of 17 years, necessitating vascular surgical intervention 1 year later because of disease progression. Histological examination of the aorta disclosed widespread atherosclerosis and high levels of gene expression of both T-helper cell type (Th) 1- and Th2-derived cytokines. This suggests that a highly stimulated systemic immune response including increased production of both Th1- and Th2-derived cytokines such as interferon-gamma and interleukin-4 may result in severe atherosclerotic lesions at a very young age. In addition, the patient developed a peripheral T-cell lymphoma at the age of 18 years. Neither systemic atherosclerosis nor T-cell lymphoma has been reported in association with ALHE. It is suggested that a highly stimulated dysfunctional immune response may play a key role in persistent inflammatory disease and premature development of atherosclerosis as well as malignant transformation of T cells.

Adolescent↗

Type I IgE receptor, interleukin 4 receptor and interleukin 13 polymorphisms in children with nephrotic syndrome.

Polymorphisms in the genes encoding the high-affinity IgE receptor, the interleukin 4 (IL4) receptor and IL13 can be associated with the development of asthma and allergy. Although several studies have described an association between atopy and idiopathic childhood nephrotic syndrome (NS), it is not clear whether this association is of a causal nature. Furthermore, it is not known whether these polymorphisms are associated with the clinical course of NS. A total of 84 children (52 male and 32 female; mean age 12.1 years) with NS were included in the present study. Of these, 78 could be classified as either atopic or non-atopic. Atopy was defined by elevated IgE levels (>100 k-units/l) and/or a positive history of atopy (33 of 78 patients). DNA was extracted from blood collected in EDTA tubes, and polymorphisms at positions 50 and 551 of the IL4 receptor, position 110 of IL13 and position 181 of the high-affinity IgE receptor were investigated by sequence-specific PCR or direct sequencing. Although we noted a strong tendency towards a higher allele frequency of polymorphisms in children with atopy and NS compared with children with NS but without atopy (IL4 50, 30% compared with 18%; IL4 551, 39% compared with 31%; IL13 110, 45% compared with 33%; IgE 181, 12% compared with 13%), these differences did not reach statistical significance. There were no differences in the frequency of polymorphisms between the different clinical courses of NS (frequent relapsers, steroid-dependent or steroid-resistant NS). We conclude that polymorphisms in the IL4 receptor, the high-affinity IgE receptor and IL13 do not seem to predict the clinical course of NS, despite the fact that serum IgE elevations are more frequent in patients with NS than in normal control subjects. The investigated polymorphisms may contribute to the IgE switch in patients with NS.

Adolescent↗

Analysis of cognitive and motor functioning during pubertal development: a new approach.

We investigated cognitive-motor abilities in 303 (156 female) school children from Zagreb, Croatia, in the age span 10 to 14 years using a newly developed chronometrical reactionmeter system (CRD). The following tests were applied: CRD-311 (simple visual discrimination of signal location), CRD-324 (short-term memory actualisation), CRD-21 (simple convergent visual orientation), and CRD-11 (arithmetically conceptualised/operationalised convergent thinking). In both gender a statistically significant age related improvement of the performance for time related parameters (minimum time of test item solving (MT), total ballast (TB), and total time of test solving (TT) was observed. In contrast, the number of errors (NE), which was the only non-time related parameter tested, did not significantly change with age. Significant differences between boys and girls were observed for the time related parameters TB and MT. TB was significantly lower in girls, whereas boys tended to be faster in MT measurements. In TT as a composed measure of the mentioned parameters, no major differences were observed. We conclude that the CRD system is a new useful tool for investigating the complexity of cognitive-motor abilities in children. Our cross-sectional study demonstrated that the time-related parameters were significantly affected by age and gender during puberty.

Adolescent↗

Undertreatment of cardiac risk factors in adolescents with renal failure.

Cardiovascular disease (CVD) is the most common cause of death in adults with end-stage renal disease and after renal transplantation, and the relative excess of mortality is greatest in the young. The most likely explanation is the dramatic accumulation of both classical and uremic risk factors leading to atherosclerosis, uremic vasculopathy, and uremic cardiomyopathy. Prospective studies have established the significance of classical and uremic risk factors for the occurrence of CVD in the normal population and in the population with chronic renal disease alike. However, whether and to what degree modification of risk factors by therapeutic intervention can lower morbidity and mortality rates is as yet unknown.

Adolescent↗

Analysis of muscle strength and bone structure in children with renal disease.

Bone structure and muscular strength of 30 children with renal disease were investigated by peripheral computed tomography and grip strength. Sixteen children suffered from nephrotic syndrome (NS) and had previously been treated with corticosteroids. Fourteen children suffered from chronic renal failure (CRF) ranging from mild renal failure to end-stage renal disease. Six children had received kidney transplants and corticosteroids for immunosuppression. There was a significant decrease in grip strength of children with NS (SD -0.91+/-1.5; P=0.042) and children with CRF (SD -1.38+/-1.4; P<0.001) compared with normal children. Furthermore, there was a significant correlation between cortical area and grip strength in all children with renal disease (r=0.92; P<0.0001). Trabecular bone mineral density did not correlate well with grip strength. These findings resemble results found in healthy children. Trabecular bone mineral density was significantly elevated in children with CRF compared with normal children (SD 1.14+/-1.4; P=0.008). Grip strength as a marker of muscle mass and cortical area as a marker of bone strength correlate well in children with renal disease, similar to the correlation in healthy children. Grip strength is significantly lower in children with NS and CRF compared with normal children. These data suggest that muscular impairment could be involved in renal osteopathy.

Adolescent↗

A stepwise approach to the treatment of early onset nephrotic syndrome.

We have retrospectively reviewed our single-center experience of the treatment of early onset nephrotic syndrome (NS). From 1991 to 1998, ten children with NS were treated. Kidney biopsy showed focal sclerosis (n=1), diffuse mesangial sclerosis (n=7), and congenital NS of the Finnish type (n=2). Associated conditions included incomplete Drash syndrome (n=1), Galloway-Mowat syndrome (n=1), and severe mental and motor retardation of unknown origin (n=3). From 1991 to 1997, five children with NS were treated. Bilateral nephrectomy (NX) was performed in three, one patient with severe retardation died at 4 years and NX was not performed in one patient who showed satisfactory growth and development. Three of these children were dialyzed and two were successfully transplanted. One patient was transplanted without previous dialysis. From 1997 to 1998, five children were treated with a regimen that included captopril and indomethacin (CAPTO/INDO). CAPTO/ INDO was successful in increasing serum protein in all patients and producing growth and development in four patients. In two patients CAPTO/INDO was successful only after unilateral NX. Our experience indicates that CAPTO/INDO may be a valuable treatment in patients with early onset NS. An individualized stepwise approach including unilateral NX should be considered to achieve optimal results.

Age of Onset↗

MR cholangiography in children with autosomal recessive polycystic kidney disease.

BACKGROUND: Magnetic resonance cholangiography (MRC) is a relatively new, non-invasive imaging technique of the biliary tree that has shown good correlation with endoscopic retrograde cholangiopancreatography. The liver manifestation of autosomal recessive polycystic kidney disease (ARPKD) is congenital hepatic fibrosis (CHF). CHF may be accompanied by Caroli's disease, which is characterised by a non-obstructive dilation of the intrahepatic bile ducts. OBJECTIVE: A prospective study was conducted to determine the presence and extent of Caroli's disease in children with ARPKD. MATERIALS AND METHODS: Seven children with ARPKD aged from 3.0 to 10. 1 years were examined. CHF was confirmed in all biopsied cases (5 of 7). All children had been followed by repeated abdominal US examinations for many years. The MR examination included a morphological imaging study using a T2-weighted turbo spin-echo sequence and a heavily T2-weighted inversion-recovery turbo spin-echo sequence with three-dimensional maximum intensity projection (MIP) reconstructions for MRC. RESULTS: The diagnosis of Caroli's disease could be made in one case by US; in two other children Caroli's disease was suspected, but the differentiation from hepatic cysts was not possible. By MRC, Caroli's disease could be diagnosed in three of seven children. Furthermore, MRC with MIP reconstructions demonstrated the extent of the disease by showing the entire biliary tree from different angles. CONCLUSIONS: MRC is a valuable method to establish the diagnosis and demonstrate the extent of Caroli's disease.

Bile Ducts, Intrahepatic↗

Probucol for treatment of hyperlipidemia in persistent childhood nephrotic syndrome. Report of a prospective uncontrolled multicenter study.

In a prospective, uncontrolled multicenter study, we have evaluated the effects of probucol on hyperlipidemia, proteinuria, and glomerular filtration rate (GFR) in hyperlipidemic children with persistent nephrotic syndrome. Probucol was started for a total of 12 weeks in 8 children and for 24 weeks in 14 children. Lipoprotein profiles, serum malondialdehyde (MDA) levels, proteinuria, renal function, and electrocardiogram were monitored every 4 weeks. Side effects were recorded by questionnaire. Treatment was completed by 7 of 8 patients for 12 weeks and by 7 of 14 children for 24 weeks. After 12 weeks, the mean serum concentrations of triglycerides (-15%), total cholesterol (-25%), very low-density lipoprotein-cholesterol (-27%), low-density lipoprotein-cholesterol (-23%), and high-density lipoprotein-cholesterol (-24%), as well as apolipoprotein (apo) A-I (-19%), apo B (-21%), and MDA (-32%) were reduced. The positive effects of probucol on the lipoprotein profile persisted over 24 weeks; however, there was no significant effect on either proteinuria or GFR. In conclusion, probucol had beneficial effects on lipoproteins and lipid peroxidation, but improved neither proteinuria nor GFR. The drug was generally tolerated well, but had to be discontinued because of a prolonged QT interval in 4 of 22 patients.

Adolescent↗

Should hyperlipidemia in children with the nephrotic syndrome be treated?

The pathogenesis, clinical significance, and treatment options of the disturbances in lipid metabolism in children with persistent nephrotic syndrome are reviewed. The lipoprotein profile is characterized by elevations of total plasma cholesterol and often triglycerides, elevated very low-density lipoprotein and low-density lipoprotein cholesterol, whereas high-density lipoprotein-cholesterol levels are variable; plasma levels of the atherogenic and thrombogenic lipoprotein(a) are also elevated. The pathophysiology of nephrotic dyslipoproteinemia is multifactorial, including both an increased hepatic synthesis and a diminished plasma catabolism of lipoproteins. There is a rationale for treatment, since dyslipidemia may contribute to the development of atherosclerosis and the progression of chronic renal failure. However, the benefits of treatment with lipid-lowering drugs have not been proven. Short-term studies in adults with nephrotic syndrome have documented safety and efficacy of lipid-lowering drugs, including hydroxymethylglutaryl-CoA reductase inhibitors ("statins"), bile acid sequestrants, fibric acids, fish oil, and probucol. Statins are the most-effective mediation, resulting in a decrease of total cholesterol levels by about 30%-40%. Prospective controlled studies in children evaluating efficacy and safety of lipid-lowering drugs are needed.

Child↗

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.

Adolescent↗