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Biomedical subjects

C H Schröder

Publications and source records attributed to C H Schröder.

At least 19 recordsLinked to original sources
PubMed2004

Children with chronic renal failure have reduced numbers of memory B cells.

Reduced serum IgG and subclass levels have been demonstrated in children with chronic renal failure. To study possible causes of this reduction, we analysed B cell subset composition, T helper cell frequencies and immunoglobulin (Ig) production capacity in vitro in children with chronic renal failure, with or without dialysis treatment. B cell subsets were characterized by determining CD27, IgM, IgD and CD5 expression within the CD19(+) population. Intracellular expression of interferon (IFN)-gamma, interleukin (IL)-2 and IL-4 in PMA/ionomycin-stimulated peripheral blood mononuclear cells (PBMC) was used to evaluate T helper frequencies. The capacity of B cells to secrete Ig in vitro was determined by measuring IgG(1), IgG(2) and IgM in culture supernatants of anti-CD2/CD28 monoclonal antibody (MoAb)- or SAC/IL-2-stimulated PBMC. Memory B cell numbers (identified as percentage or absolute number of CD19(+) IgM-IgD- or CD19(+)CD27(+) lymphocytes) were lower in children treated with haemodialysis (HD), peritoneal dialysis (PD) and children with chronic renal failure before starting dialysis treatment (CRF) compared to healthy controls (HC) (P < 0.05). Compared with HC, CD5(+) (naive) B cells were reduced in HD-treated patients but not for PD or for children with chronic renal failure before starting dialysis treatment (CRF). No significant differences in CD4(+) T helper cell subsets were found between the groups. However, CRF children had a higher percentage of IFN-gamma producing CD8(+) T lymphocytes compared to HC (P = 0.02). Finally, IgG(1), IgG(2) and IgM production in vitro was similar in the four groups. In conclusion, significantly lower numbers of memory type B cells were found in children with chronic renal failure compared to healthy controls. This reduction may contribute to the low Ig levels found in these children.

Adolescent↗
PubMed2003

Is biopsy required prior to cyclophosphamide in steroid-sensitive nephrotic syndrome?

AIM: The present studywas designed to retrospectively evaluate the use of renal biopsies prior to cyclophosphamide therapy. The aim of the study was to determine in how many cases histological outcome of the biopsies had subsequently changed the decision to treat or refrain from treatment. PATIENTS AND METHODS: Between January 1980 and September 2001, 85 children with steroid-sensitive nephrotic syndrome (SSNS) underwent a renal biopsy in the University Hospitals of Utrecht and Nijmegen before the start of an 8-week cyclophosphamide treatment. MCNS was suspected in all children because of the following criteria: edema, proteinuria, hypoalbuminemia, absence of macroscopic hematuria and in rare cases microscopic hematuria, no permanent hypertension, normal C3 serum level, a normal glomerular filtration rate as determined by creatinine clearance and age > 1 year. Cyclophosphamide therapy was indicated because of a frequently relapsing (FR) course of illness in 8 children, because of steroid dependence (SD) in 22 children and because of combined FR and SD in 55 children. Steroid-resistant children were excluded from this study. RESULTS: Histology confirmed the diagnosis MCNS in 84 out of 85 children. In addition to MCNS, IgA deposits were observed in renal specimens of 2 children. In 1 SD child, the initial diagnosis MCNS was changed 3 years later when a repeated biopsy showed progression into focal segmental glomerulosclerosis (FSGS). CONCLUSION: In summary, no renal biopsy is required prior to cytotoxic therapy in children with uncomplicated steroid-sensitive nephrotic syndrome.

Adolescent↗
PubMed2001

Peptide aptamers targeting the hepatitis B virus core protein: a new class of molecules with antiviral activity.

A substantial proportion of the worldwide liver cancer incidence is associated with chronic hepatitis B virus (HBV) infection. The therapeutic management of HBV infections is still problematic and novel antiviral strategies are urgently required. Using the peptide aptamer screening system, we aimed to isolate new molecules, which can block viral replication by interfering with capsid formation. Eight peptide aptamers were isolated from a randomized expression library, which specifically bound to the HBV core protein under intracellular conditions. One of them, named C1-1, efficiently inhibited viral capsid formation and, consequently, HBV replication and virion production. Hence, C1-1 is a novel model compound for inhibiting HBV replication by blocking capsid formation and provides a new basis for the development of therapeutic molecules with specific antiviral potential against HBV infections.

Amino Acid Sequence↗
PubMed2001

Hepatitis B virus nucleic acids circulating in the blood: distinct patterns in HBs carriers with hepatocellular carcinoma.

Circulating nucleic acids in serum and plasma are common in a variety of disease conditions. Here, we focus (i) on our approach for the detection of various hepatitis B virus (HBV)-related nucleic acids in liver tissue and in serum, (ii) on the progression of the chronic HBV infection, (iii) on the relation of HBV-specific nucleic acids circulating in the blood of patients with hepatocellular carcinoma, and in general (iv) on the diagnostic potential of circulating HBV nucleic acids.

Amino Acid Sequence↗
PubMed2001

Circulating hepatitis B virus nucleic acids in chronic infection : representation of differently polyadenylated viral transcripts during progression to nonreplicative stages.

PURPOSE: Beside the established maturation of hepatitis B virus (HBV) transcripts at a polyadenylation signal downstream of the HBV x protein open reading frame, maturation at an internal polyadenylation signal has been observed in the chronically infected liver. In the present study, it was the aim to identify the respective circulating full-length and truncated transcripts in plasma/serum of carriers. EXPERIMENTAL DESIGN: Nucleic acids extracted from sera were analyzed using established PCR and reverse transcription-PCR procedures targeted to HBV x protein gene regions. Amplification products were cloned and sequenced. RESULTS: Base substitution patterns were determined, which indicated infection stages advanced to different degrees regardless of the transcript type analyzed. HBV full-length RNA (fRNA) showed a high correlation with hepatitis B e antigen and viral DNA, indicative for a replicative infection. In contrast, truncated RNA (trRNA) appeared to be independent of hepatitis B e antigen and showed only a weak association with circulating viral DNA. No correlation was observed between the levels of trRNA and the apparent liver damage as reflected by alanine transaminase levels. An age-dependent representation of fRNA and trRNA was observed: fRNA decreased progressively to low levels, whereas trRNA remained at comparably high values. trRNA and RNA not polyadenylated at either of the two polyadenylation signals were detected even in the absence of any other conventional HBV seromarker, including viral DNA. This was shown for patients with cryptogenic cirrhosis and hepatitis C virus carriers. CONCLUSIONS: The identification of HBV RNA in human serum has a diagnostic potential for apparent and for inapparent infection stages.

Adolescent↗
PubMed2000

[Acute renal insufficiency caused by bilateral ureteral obstruction after appendectomy in a 6-year old boy].

A 6-year-old boy developed macroscopic haematuria on the 4th day after appendectomy for acute appendicitis, at which the appendix was found to be perforated. During the next few days the urine secretion decreased and malaise, pain in the lower abdomen, nausea and vomiting occurred. On a management of ample fluid administration, the urine secretion recovered and the symptoms subsided in a few days. In the early postoperative stage after appendectomy in children the possibility should be kept in mind of the development of acute renal insufficiency due to bilateral ureteral obstruction as a result of oedema of the posterior bladder wall, even if by means of ultrasonography only mild to moderate abnormalities are noted. Awaiting decompression by means of the introduction of bilateral ureteric stents, in order to prevent irreversible renal damage, supportive therapy with fluid administration depending on the diuresis seems indicated.

Acute Kidney Injury↗
PubMed2000

Clinical experience with icodextrin in children: ultrafiltration profiles and metabolism.

Icodextrin use in adults provides sustained ultrafiltration (UF) in long-term dwells. No information is available on UF and metabolism in children. In 11 children, a volume of 1,049+/-138 ml/m2 of the study fluid (1.36% glucose, 7.5% icodextrin, 3.86% glucose) was administered for 12 h. Net UF with icodextrin (339+/-147 ml/1.73 m2) did not differ from UF with 3.86% glucose (450+/-306 ml/1.73 m2, P=0.53) and was higher than UF with 1.36% glucose (-87+/-239 ml/1.73 m2, P=0.003). Icodextrin added 0.52+/-0.07 to the weekly Kt/V. Over 6 weeks, icodextrin was used for 12-h daytime dwell. Total icodextrin reached a steady-state level of 2.91+/-1.22 g/l at 2 weeks. The main icodextrin metabolites were maltose, maltotriose, and maltotetraose. After 2 weeks, steady state levels were 2.02+/-0.66 mmol/l, 1.46+/-0.35 mmol/l, and 0.45+/-0.12 mmol/l. No icodextrin or metabolites were detectable 4 weeks after the study. We conclude that 7.5% icodextrin is capable of maintaining UF during 12-h dwell in children and is comparable to UF obtained with 3.86% glucose. Steady-state levels of icodextrin and metabolites were reached at 2 weeks and disappeared after the study.

Adolescent↗
PubMed2000

Oral L-carnitine does not decrease erythropoietin requirement in pediatric dialysis.

The use of recombinant human erythropoietin (rhEPO) has greatly facilitated the treatment of anemia in children with chronic renal failure, but is expensive. Several reports on adult patients have shown that supplementation with L-carnitine can decrease the requirement for rhEPO. The objective of this study was to investigate the effect of oral supplementation with L-carnitine on the rhEPO requirement in children on dialysis. We investigated 16 children on dialysis (11 hemodialysis, 5 peritoneal dialysis) with a median age of 10.2 years. All children were stable on rhEPO treatment at least 3 months before study entrance. After obtaining baseline data, all children were supplemented with L-carnitine 20 mg/kg/day. Data were collected for 26 weeks. Follow-up was completed for 12 patients (8 hemodialysis, 4 peritoneal dialysis). At baseline free carnitine (32+/-18 micromol/l) and total carnitine levels (54+/-37 micromol/l) were normal. At the end of the study free carnitine levels had increased to 97+/-56 micromol/l (P<0.05) and total carnitine levels to 163+/-90 micromol/l (P<0.05). There was no significant change in rhEPO requirement. Hemoglobin level or hematocrit did not change significantly during the study. In conclusion we could not demonstrate a beneficial effect of supplementation with L-carnitine on rhEPO requirement in children on dialysis.

Administration, Oral↗
PubMed2000

Overexpression of p53 protein is not directly related to hepatitis B x protein expression and is associated with neoplastic progression in hepatocellular carcinomas rather than hepatic preneoplasia.

p53 mutations and binding of p53 to hepatitis B virus (HBV) x protein (HBx) have been suggested as alternative mechanisms of development of hepatocellular carcinomas (HCCs) in man, both processes resulting in intracellular accumulation of the protein which is detectable by immunohistochemical approaches. We have examined p53 expression in 149 explanted human livers, including 39 cases infected with HBV and 35 bearing HCC. p53 was demonstrated immunohistochemically in 51% of HCC samples (18/35), localized mainly in fast growing poorly differentiated areas. Accumulation of mutant p53 was verified by immunoprecipitation in most of the positive HCC samples (14/15), implying occurrence of p53 mutations. No cells positive for p53 were found in 354 preneoplastic hepatocellular lesions examined. This indicates that p53 mutation is associated with progression, rather than early development, of HCC in the low-aflatoxin B(1)-exposed region. The intracellular distribution patterns of p53 and HBx were different, with the former within nuclei and the latter confined to cytoplasmic compartment. HBx did not coimmunoprecipitate with p53. These data indicate that p53-HBx binding is infrequent, if it really occurs, in HBV-infected human liver, and that it cannot be a common mechanism of HBV-associated hepatocarcinogenesis. In addition, p53 accumulation was also observed in some parenchymal and ductular (oval) cells in cirrhotic livers and, more frequently, in fulminant hepatitis, being independent of HBx expression, and seemingly associated with the damage and/or regeneration of liver parenchyma, perhaps merely reflecting a cellular stress response.

Carcinoma, Hepatocellular↗
PubMed2000

Immunoglobulins in chronic renal failure of childhood: effects of dialysis modalities.

BACKGROUND: It is not clear whether low serum levels of IgG (subclasses), previously demonstrated in children on peritoneal dialysis (PD), are related to the PD procedure or to factors associated with chronic renal failure (CRF). The aim of our study was to analyze the effect of PD on serum and PD effluent (PDE) IgG and subclass levels in children with end-stage renal failure. METHODS: We measured albumin, IgG, IgA, IgM, and IgG subclasses in serum and PDE from children on PD (N = 40) and compared the serum values with those of children treated with hemodialysis (HD, N = 23) or presenting with CRF but not yet dialyzed (CRF; N = 63), and with a group of healthy controls (HCs; N = 67). Sixteen PD children could be followed sequentially from before starting PD and eight during a peritonitis episode. RESULTS: Forty percent of the PD children showed reduced serum IgG2 levels (P = 0.0003) compared with 35% in HD (P = 0.006), 33% in CRF (P = 0.001), and 9% in HC children. IgG1 deficiencies were observed in 25% of PD patients (P < 0.0001), 4% of HD (P = NS), 16% of CRF (P = 0.0005), and 0% of HC children. IgG3 and IgG4 deficiencies were observed less frequently. Peritoneal clearances were similar for total IgG, IgG1, IgG2, and IgG4, but were lower for IgG3 (P < 0.05). No relationships were found between clearances and age or duration of PD treatment. Total IgG (P = 0. 003) and IgG1 (P = 0.002) levels declined just after starting PD. Peritonitis was associated with temporarily increased peritoneal loss of Ig, while the serum concentrations were unaffected. No significant relationship was found between the peritonitis incidence and reduced IgG or subclasses. However, all children with two or more peritonitis episodes per year had a reduced Ig level. CONCLUSIONS: Although the mean serum concentrations of immunoglobulins were normal in all studied groups, a deficiency of one or more IgG subclasses was present in all groups with renal failure, suggesting inhibition of their synthesis by the uremic state. Ig deficiencies were more frequently found in PD, likely caused by protein loss in PDE. A high peritonitis incidence was associated with reduced serum Ig levels.

Acute Disease↗
PubMed2000

Autosomal dominant Alport syndrome caused by a COL4A3 splice site mutation.

BACKGROUND: Alport syndrome (AS) is a clinically and genetically heterogeneous renal disorder, predominantly affecting the type IV collagen alpha 3/alpha 4/alpha 5 network of the glomerular basement membrane (GBM). AS can be caused by mutations in any of the three genes encoding these type IV collagen chains. The majority of AS families (85%) are X-linked (XL-AS) involving mutations in the COL4A5 gene. Mutations in the COL4A3 and COL4A4 genes cause autosomal recessive AS (AR-AS), accounting for approximately 14% of the cases. Recently, autosomal dominant AS (AD-AS) was linked to the COL4A3/COL4A4 locus in a large family. METHODS: COL4A3 and COL4A4 cDNAs were generated by nested reverse transcription-polymerase chain reaction and were analyzed by DNA sequence analysis. Denaturating high-performance liquid chromatography (DHPLC) was used for mutation and segregation analysis at the genomic DNA level. RESULTS: In the AD-AS family, a splice site mutation resulting in skipping of exon 21 of the COL4A3 gene was detected. The mutation does not alter the reading frame and is predicted to result in a COL4A3 chain with an internal deletion. CONCLUSION: As the NC domain is intact, this chain may be incorporated and distort the collagen triple helix, thereby causing the dominant effect of the mutation. The finding of a specific COL4A3 mutation in AD-AS completes the spectrum of type IV collagen mutations in all genetic forms of AS.

Adult↗
PubMed1999

Ceftriaxone-associated nephrolithiasis and biliary pseudolithiasis.

Biliary pseudolithiasis has been reported in patients who received ceftriaxone therapy. In addition to biliary sludge formation occasional reports of ceftriaxone-induced nephrolithiasis have been published. In general, these adverse effects will develop after seven to ten days of treatment. We report on a seven-year-old boy with ceftriaxone-associated biliary pseudolithiasis and nephrolithiasis four days after initiation of treatment. Patients receiving a high dose of ceftriaxone and developing colicky abdominal pain should be considered for ultrasound and a change in antibiotic therapy if appropriate.

Bile Duct Diseases↗
PubMed1999

Intraperitoneal hypercoagulation and hypofibrinolysis is present in childhood peritonitis.

An increased rate of obstruction of peritoneal dialysis catheters is observed during peritonitis. Hypercoagulation and hypofibrinolysis may explain this increased occurrence. We studied plasminogen activator inhibitor type 1 antigen (PAI-1), tissue-type plasminogen activator antigen (t-PA), D-dimer (DD), plasmin-alpha2-antiplasmin complexes (PAP), and thrombin-antithrombin III complexes (TAT) in 7 children with peritonitis (group A) and 12 children during stable peritoneal dialysis (group B). Albumin, beta2-microglobulin, IgG, and alpha2-macroglobulin were measured for baseline transperitoneal protein transport. After a dwell of 6 h with 1.36% Dianeal, dialysate and serum samples were collected. Dialysate to plasma ratios of all proteins were calculated. During peritonitis (group A) TAT was higher: 34.7 versus 22.0 (P=0.01). PAI-1 was increased in group A: 76.5 versus 22.9 (P=0.004). PAP was decreased during peritonitis (group A): 24.9 versus 39.3 (P=0.01). In group A, DD were decreased. 10.8 versus 26.7 (P=0.002). t-PA was similar in both groups (23.7 in group A vs. 27.7 in group B; P=0.26). In both groups TAT, PAI-1, t-PA, PAP, and DD were significantly higher than in baseline transperitoneal transport, suggesting intraperitoneal production. Hypercoagulability and hypofibrinolysis were present during peritonitis compared with the control situation.

Adolescent↗
PubMed1999

Treatment of hyperhomocysteinemia in children on dialysis by folic acid.

Adult patients with renal failure have a high total homocysteine concentration in plasma. Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. Folic acid lowers the homocysteine concentrations in plasma in hyperhomocysteinemia. Whether this results in a reduced risk for cardiovascular diseases remains to be proven by intervention studies. In the present study we investigated: (1) if homocysteine concentrations are elevated in the plasma of children with renal failure and (2) the influence of folic acid administration on the plasma homocysteine concentration. The plasma homocysteine concentration was measured in 21 children, 9 on hemodialysis and 12 on peritoneal dialysis, before and 4 weeks after treatment with 2.5 mg folic acid daily. Healthy children (234) constituted the control group. In controls the median homocysteine concentration was 9.1 micromol/l (range 4.3-20.0 micromol/l). The median plasma homocysteine concentration in patients before folic acid treatment was 20.0 micromol/l (Q1-Q3 13.7-26.0; Q, quartile). After 4 weeks of folic acid treatment the median plasma homocysteine concentration was 12.0 micromol/l [Q1-Q3 9.8-14.3 (P<0.0001 Wilcoxon signed rank test)]. There was no significant difference between hemodialysis and peritoneal dialysis patients. Children with renal failure treated with hemodialysis or peritoneal dialysis have elevated plasma homocysteine concentrations, but this is significantly reduced after administration of 2.5 mg folic acid daily for 4 weeks. It is suggested that folic acid be added to the treatment of children with renal failure, although a beneficial effect still has to be proven. The required dose needs further study.

Child↗
PubMed1999

Identification of COL4A5 defects in Alport's syndrome by immunohistochemistry of skin.

BACKGROUND: The COL4A3-COL4A4-COL4A5 network in the glomerular basement membrane is affected in the inherited renal disorder Alport's syndrome (AS). Approximately 85% of the AS patients are expected to carry a mutation in the X-chromosomal COL4A5 gene and 15% in the autosomal COL4A3 and COL4A4 genes. The COL4A5 chain is also present in the epidermal basement membrane (EBM). It is predicted that approximately 70% of the COL4A5 mutations prevent incorporation of this chain in basement membranes. METHODS: We investigated whether or not COL4A5 defects could be detected by immunohistochemical analysis of the EBM. Punch skin biopsies were obtained from 22 patients out of 17 families and two biopsy specimens from healthy males were used as controls. RESULTS: In four cases with the COL4A5 frameshift or missense mutations, the COL4A5 chain was either lacking from the EBM (male) or showed a focally negative pattern (female). In three other patients with a COL4A5 missense mutation, a COL4A3 and a COL4A4 mutation, respectively, the COL4A5 staining was normal. A (focally) negative EBM-COL4A5 staining was found in three patients of six families with a diagnosis of AS and in one family of a group of four families with possible AS. CONCLUSIONS: The (focal) absence of COL4A5 in the EBM of skin biopsy specimens can be used for fast identification of COL4A5 defects. Combined with polymorphic COL4A5 markers, both postnatal and prenatal DNA diagnosis are possible in the family of the patient.

Antibodies, Monoclonal↗