PubMed Health⌕ Search

Biomedical subjects

Stefan Wirth

Publications and source records attributed to Stefan Wirth.

At least 19 recordsLinked to original sources
PubMed2006

Prevalence of autoantibodies and the risk of autoimmune thyroid disease in children with chronic hepatitis C virus infection treated with interferon-alpha.

AIM: To evaluate the prevalence of autoantibodies in chronic hepatitis C virus (HCV)-infected children focusing on thyroid autoimmunity. METHODS: We investigated the prevalence of auto-antibodies in 123 chronic HCV-infected children before, during and after monotherapy with interferon-alpha (IFN-alpha) or combined treatment with interferon-alpha or peginterferon-alpha and ribavirin. Besides antibodies against smooth muscle (SMA), nuclei (ANA), and liver/kidney microsomes (LKM), the incidence of anti-thyroid peroxidase antibodies as well as thyroid function parameters (TSH, FT3 and FT4) were determined. RESULTS: We found that 8% of children had autoantibodies before treatment. During treatment, 18% of children were found positive for at least one autoantibody; 15.5% of children developed pathologic thyroid values during IFN-alpha treatment compared to only one child before therapy. Six children had to be substituted while developing laboratory signs of hypothyroidism. CONCLUSION: Our data indicate a strong correlation between interferon-alpha treatment and autoimmune phenomena, notably the emergence of thyroid antibodies. The fact that some children required hormone replacement underlines the need of close monitoring in particularly those who respond to therapy and have to be treated for more than 6 mo.

Adolescent↗
PubMed2006

Prevalence of hepatitis B virus precore stop codon mutations in chronically infected children.

AIM: To find out whether there is a significant difference in the prevalence of the precore stop codon mutation between HBeAg positive and anti-HBe positive children. METHODS: We investigated a large pediatric population of 155 European children (mean age 10.9 years) with chronic hepatitis B by PCR and direct sequencing. Ninety were HBeAg positive and 65 had seroconversion to anti-HBe. Additionally genotyping was performed. RESULTS: Seventy-four (48%) of the sequenced HBV strains were attributed to genotype D and 81 (52%) to genotype A. In the group of 90 HBeAg positive patients, 2 (2.2%) 1896-G-to-A transitions leading to precore stop codon mutation were found, and in the group of 65 anti-HBe positive children, 5 (7.7%) were identified harbouring HBeAg-minus mutants. The difference was not statistically significant (P = 0.13). CONCLUSIONS: HBeAg minus variants as predominant viral HB strains play a minor role in the course of chronic hepatitis B in European children.

Alanine Transaminase↗
PubMed2006

Comparison of different patient positioning strategies to minimize shoulder girdle artifacts in head and neck CT.

The purpose of this study was to analyze different patient positioning strategies for minimizing artifacts of the shoulder girdle in head and neck CT. Standardized CT examinations of three positioning groups were compared (P: patients pushed their shoulders downwards; D: similar optimization by a pulling device; N: no particular positioning optimization). Parameters analyzed were the length of the cervical spine not being superimposed by the shoulder girdle as well as noise in the supraclavicular space. In groups P and D, the portion of the cervical spine not superimposed was significantly larger than in group N (P: 10.4 cm; D: 10.6 cm; N: 8.5 cm). At the supraclavicular space, noise decreased significantly (P: 12.5 HU; D: 12.1 HU; N: 17.7 HU). No significant differences between the two position-optimized groups (P and D) were detected. Optimized shoulder positioning by the patient increases image quality in CT head and neck imaging. The use of a pulling device offers no additional advantages.

Artifacts↗
PubMed2006

Hard disk online caches in picture archiving and communication systems archives: how big is beautiful?

The objective of our study was to support algorithmic recommendations for the appropriate sizing of picture archiving and communication system (PACS) caches. For a large PACS installation, a detailed analysis of current radiographic (CR), CT and MRI studies (n=400 consecutive studies, respectively) was performed. In this process every available prior examination was also considered. A new algorithmic procedure for appropriate sizing of PACS caches was developed and applied to the given cache implementation. The number of all priors was 7.6+/-12.3. Of them, 61% were relevant priors with an average age of 203+/-385 days. A basic cache (BC) that covers 12 months of current imaging results in a pre-fetching quote of 15.4% (8.6% for 24 months). In the PACS installation examined, a minimal threefold increase in cache capacity was recommended. Studies that are retrieved, prior to viewing, from the long-term archive require additional space in the extended cache (EC). An intimate and mutual interaction between hospital information system (HIS), radiology information system (RIS) and PACS minimizes this requirement and increases the time during which actual image material from the BC is available online. A basic cache size covering actual imaging of 12 months up to 24 months is recommended. The parameters governing the individual dimensions of both cache spaces and a mathematical algorithm are demonstrated.

Algorithms↗
PubMed2006

Cobalt(II)-catalyzed cross-coupling between polyfunctional arylcopper reagents and aryl fluorides or tosylates.

[reaction: see text] Organocopper compounds prepared by the transmetalation of functionalized arylmagnesium halides with CuCN.2LiCl undergo smooth cross-coupling reactions with aryl fluorides and tosylates bearing a carbonyl function in the ortho position in the presence of Co(acac)(2) (7.5 mol %), Bu(4)NI (1 equiv), and 4-fluorostyrene (20 mol %) as promoters in DME/THF/DMPU leading to polyfunctional aromatics or heterocycles.

Journal Article↗
PubMed2006

Prevalence of hepatitis C virus infection in children admitted to an urban hospital.

BACKGROUND AND AIM: Hepatitis C infection is a global health problem affecting about 3% of the world's population. However, very little data exists on the prevalence of hepatitis C virus infection in childhood. METHODS: We performed a cross-sectional study in 2000 children and adolescents who were treated as in- or out patients in our hospital. Blood samples were collected between February 2002 and June 2004 and were tested for HCV antibodies (anti-HCV). Positive samples were further investigated by HCV specific PCR and Western blot assay. RESULTS: Mean age of children was 8.1 years. 908 (45%) were female and 1092 (55%) male. One thousand eight hundred and ninety-eight were Caucasian, 37 African, and 65 Asian. 16 (0.8%) tested positive for anti-HCV. HCV-RNA was detectable in one child (0.05%), and three were positive in the Western blot assay (0.15%). The HCV viremic child had received multiple blood transfusions after cardiac surgery. She was asymptomatic with normal transaminases. Seroprevalence of HCV antibodies were equally distributed among boys and girls. CONCLUSIONS: The prevalence of persistent hepatitis C in children from an urban hospital in Germany is low. Most patients with HCV antibodies are not infected. Therefore, although universal screening is not warranted, it should always be performed in risk groups such as transfused children because HCV infection in childhood is usually asymptomatic.

Adolescent↗
PubMed2006

Relationship between viral load and genotypes of hepatitis B virus in children with chronic hepatitis B.

OBJECTIVE: We evaluated the prevalence and clinical significance of hepatitis B virus (HBV) genotypes in children with chronic hepatitis B. METHODS: Hepatitis B virus genomes of 249 hepatitis Be antigen-positive chronic hepatitis B surface antigen carriers were genotyped based on restriction fragment length polymorphism. Genotypes were correlated with corresponding values for alanine aminotransferase levels, quantitative HBV DNA and histological findings. RESULTS: One hundred and sixty-two boys and 87 girls (mean age, 7.2 years) were studied. Ninety-six percent were attributed to HBV genotypes A (32.5%) or D (63.5%). The remaining were classified as genotypes B, C, E and F. There was no significant difference in both alanine aminotransferase levels and histological findings among different genotypes. However, there was a clear association between very high HBV DNA levels and individuals with genotype D (P = 0.006). Mean time follow-up of 3.6 years showed later anti-HBe seroconversion in patients with genotype D than in those with genotype A (58% vs 37%). CONCLUSIONS: Compared with children with genotype A, children with genotype D showed a significantly higher viral load. Inasmuch as a relationship exists between viral load and response to treatment in children infected through vertical transmission, children with genotype D have to be carefully monitored. Long-term studies are needed to determine whether these patients are at risk of a poorer outcome.

Adolescent↗
PubMed2006

Depiction of low-contrast detail in digital radiography: comparison of powder- and needle-structured storage phosphor systems.

PURPOSE: We sought to evaluate the low-contrast performance of a newly developed needle image plate/line scanner (NIP) computed radiography system in comparison with a standard powder image plate/flying-spot scanner (PIP) system. MATERIALS AND METHODS: A total of 36 images of a CDRAD phantom, simulating low-contrast structures with different drill holes of different diameters, were obtained with both imaging systems using 9 different exposure variables. All images had window and level set to generate consistent density and contrast. In addition, multiscale contrast-dependent contrast amplification was applied to some of the images. All images obtained were printed and presented to a total of 10 observers (5 radiologists, 5 engineers/physicists), who were blinded to both the image plate and parameter setting used. The smallest detectable drill hole depth (= contrast) correctly identified was recorded for each diameter. The median values observed were calculated and tested for statistical differences between PIP and NIP using Student t test for matched pairs (level of significance P < or = 0.05). RESULTS: At all but 2 settings of the variables, NIP images depicted significantly lower contrast levels (= lower depth of drill holes) compared with PIP images. The 2 settings also showed a trend towards better low contrast depiction with NIP. In no case was low contrast performance better using PIP images. CONCLUSION: Images obtained with needle image plate/line scanner provide superior low contrast performance compared with the images obtained with powder image plate/flying-spot scanner.

Observer Variation↗
PubMed2006

Long-term results after primary stenting of distal aortic stenosis.

PURPOSE: To review the long-term results of primary stent placement in the distal aorta above the bifurcation. METHODS: Fourteen patients (8 men; mean age 62 years, range 46-82) underwent primary stent implantation performed by an interdisciplinary radiosurgical team. In 10 patients, a long-term follow-up examination consisting of patient history, clinical examination, and duplex sonography was performed. The ankle-brachial index (ABI) for the posterior tibial artery was calculated on the basis of Doppler pressure measurements. RESULTS: The clinical success rate at the first follow-up examination (mean 2.9 months, range 2.1-4.4) was 100% (n = 14). The mean baseline ABI of 0.64 +/- 0.12 had risen to 1.02 +/- 0.10 (p < 0.0001). At midterm follow-up (mean 22.8 months, range 14-42) in 12 patients, the ABI was 0.96 +/- 0.12 (p < 0.0001 versus baseline). At a mean 86 months (range 51-119) after stent treatment, the ABI in 10 patients was 0.90 +/- 0.20 (p < 0.0001 versus baseline). Over the long term, the clinical success rate was 70%. Deterioration was due to the progression of atherosclerosis distal to the aorta; duplex sonography showed no aortic restenosis or occlusion. CONCLUSION: In view of the excellent long-term results in our small series, primary stent placement in focal abdominal aortic stenosis in properly selected patients is a durable treatment. In addition, the mortality and morbidity risks are markedly reduced compared with open surgery.

Aged↗
PubMed2005

Adrenal failure followed by status epilepticus and hemolytic anemia in primary antiphospholipid syndrome.

We report on a 14 year old boy who presented with the symptoms abdominal pain, fever and proteinuria. A hematoma in the region of the right pararenal space was diagnosed. Prothrombin time and activated partial thromboplastin time were prolonged, lupus anticoagulant and anticardiolipin antibodies were positive and serum cortisol was normal. Ten days after admission the boy suddenly suffered generalized seizures due to low serum sodium. As well, the patient developed hemolytic anemia, acute elevated liver enzymes, hematuria and increased proteinuria. At this time a second hemorrhage of the left adrenal gland was documented. Adrenal function tests revealed adrenal insufficiency. We suspected microthromboses in the adrenals and secondary bleeding and treated the boy with hydrocortisone, fludrocortisone and phenprocoumon. CONCLUSION: Adrenal failure is a rare complication of APS in children with only five cases reported to date. As shown in our patient, this syndrome can manifest in a diverse set of simultaneously occurring symptoms.

Journal Article↗
PubMed2005

Peginterferon alfa-2b plus ribavirin treatment in children and adolescents with chronic hepatitis C.

Peginterferon plus ribavirin is standard therapy for adults with chronic hepatitis C. As no data are available for children, the aim of the study was to evaluate the efficacy and tolerability of peginterferon alfa-2b in combination with ribavirin in chronically infected children. Genotypes, alanine aminotransferase levels, and different routes of viral transmission were considered. In an open-labeled, uncontrolled pilot study, 62 children and adolescents (range, 2-17 years) were treated with subcutaneous peginterferon alfa-2b at a dose of 1.5 microg/kg body weight once per week plus oral ribavirin (15 mg/kg x day) for 48 weeks. Sixty-one patients completed the study. Twenty-three children discontinued therapy after 6 months according to study protocol. Sustained viral response was documented in 22 (47.8%)of 46 patients with genotype 1, in 13 (100%) of 13 with genotype 2 or 3, in 1 of 2 with genotype 4, in 19 (70.4%) of 27 children with parenteral, in 12 (48%) of 25 with vertical, and in 5 of 9 with unknown route of infection. Overall, treatment was well tolerated. Nevertheless, some side effects were present in all treated patients. Eighty-three percent had leucopenia, but only 3 individuals required dose reduction and 10.3% developed thyroid autoantibodies and thyroid dysfunction. In conclusion, combination treatment of peginterferon alfa-2b with ribavirin showed encouraging results and was well tolerated in children and adolescents with chronic hepatitis C. Weekly dosing of peginterferon alfa-2b is a considerable advance for this age group. The treatment is not approved for children. Further controlled trials are needed.

Adolescent↗
PubMed2005

Complete hepatitis B virus genome analysis in chronically infected children before and during lamivudine treatment.

It is well established that during lamivudine treatment, mutations emerge within the polymerase gene but there is little information about the selection of other mutations in the whole hepatitis B virus (HBV) genome. The aim of this study was to investigate whether mutations outside this region are selected during lamivudine treatment. The complete HBV genomes of six HBsAg positive chronically infected children were isolated from the children's sera before, at the beginning and during lamivudine treatment, amplified and sequenced directly. A change in the mutation rate and type in periods with and without treatment for one and the same patient were examined longitudinally because blood samples were taken long before treatment started. During the testing period before treatment, 12 mutations occurred within 11.7 +/- 8.1 months in all genomes, resulting in a mutation rate of 1.1 x 10(-3) substitutions per site per year. During treatment with lamivudine, 20 mutations occurred in all patients within an average period of 7.6 +/- 1.2 months, giving an average mutation rate of 1.8 x 10(-3) substitutions per site per year. The 20 mutations observed during the treatment period occurred in only 4 of the patients and only 3 patients experienced nonsense mutations during lamivudine treatment. The mutations were spread across the entire genome with a non-significant cluster during treatment in the P-ORF (18 mutations vs. 7, P = 0.073) and S-ORF (11 vs. 2, P = 0.063). Mutations causing drug resistance did not emerge. This study describes the changes in the complete HBV genome in the spontaneous course of infection and during lamivudine treatment. An increased mutation rate and the occurrence of specific mutations could not be proven for the early phase of lamivudine treatment.

Amino Acid Substitution↗
PubMed2005

The nonviral episomal replicating vector pEPI-1 allows long-term inhibition of bcr-abl expression by shRNA.

The inhibition of gene expression by RNA interference harbors a high potential for application in the therapy of human diseases. However, while exogenous application of siRNAs efficiently inhibits gene expression, these effects are only transient in mammalian cells. We designed a short hairpin RNA-expression cassette to target the bcr-abl oncogene that was then introduced into the nonviral vector system pEPI-1, which replicates episomally in the absence of selection in the bcr-abl-positive cell line K562. Forty-two days after transfection the bcr-abl- but not the cytokine-dependent growth rate was found to be drastically reduced in K562 cells. Western analysis revealed a more than 90% reduction in the expression of the fusion protein bcr-abl while the expression of the bcr protein remained unaffected. In addition, we show that the level of bcr-abl mRNA was specifically reduced in these cells for more than 90%. These results demonstrate that the vector system pEPI-1 allows specific and efficient long term gene suppression by using a short hairpin RNA transcription unit.

Base Sequence↗
PubMed2005

Detecting adverse drug reactions on paediatric wards: intensified surveillance versus computerised screening of laboratory values.

BACKGROUND: Adverse drug reactions (ADRs) contribute significantly to patient morbidity and mortality, as well as to costs for healthcare systems. Our aim was to evaluate the type and incidence of ADRs in a paediatric hospital population, comparatively ascertained by two different methodological approaches. METHODS: Our prospective study enrolled all patients admitted to two of the general children wards (46 beds) and the paediatric intensive care unit (6 beds) at the HELIOS Klinikum Wuppertal teaching hospital in Germany, over the study period of 3 months. We used two methods to detect ADRs. The intensified surveillance system relied on a trained physician conducting ward rounds and assessing patient charts. The computer-assisted screening of pathological laboratory parameters used values slightly below or above the age-specific normal range as a trigger signal for a potential ADR, which was subsequently assessed by trained personnel. RESULTS: By applying both methods simultaneously we observed that 14.1% of children experienced an ADR while they were hospitalised and 2.7% of children were admitted to hospital because of the ADR. Intensified surveillance resulted in the detection of 101 ADRs in 11.9% of patients, predominantly presenting with gastrointestinal symptoms, skin and CNS disorders; computer-assisted screening identified 45 ADRs in 5.7% of patients, mainly with drug-induced blood dyscrasia and liver damage. Furthermore, the ADRs detected by the intensified method were more severe, affected younger children and showed a closer causal attributability to the reaction than the ADRs observed by the computerised method. The spectra of drugs involved were similar, with the anti-infectives being suspected most frequently. The sensitivities of the intensified surveillance system and the computerised surveillance screening came to 67.2% and 44.8%, respectively, with computer-assisted screening having a specificity of 72.8%. The mean positive predictive value of the pathological laboratory values under surveillance by computer-assisted screening was 18.6%. Approximately 25% of ADR-related drugs administered were used for off-label indications. CONCLUSION: Using the published literature for comparison, we found that ADRs occur as frequently in paediatric patients as in adult patients. Intensified surveillance and computerised surveillance applied in the paediatric setting show substantial differences in their detection specificities. A higher number of and more severe ADRs can be detected by intensified surveillance than by computerised surveillance, but require higher personnel resources.

Child↗
PubMed2004

Complete hepatitis B virus genome analysis in HBsAg positive mothers and their infants with fulminant hepatitis B.

BACKGROUND: After perinatal transmission of hepatitis B virus, infants of anti-HBe positive HBsAg carrier mothers may develop fulminant hepatitis B. Previously it has been suggested, that fulminant hepatitis B in adults was associated with specific mutations in the HBV-genome. The aim of this study was to investigate, whether specific viral variants are associated with fulminant hepatitis B in young infants. METHODS: The complete HBV-genomes of five mothers and their infants with fulminant hepatitis were isolated from the sera, amplified and directly sequenced. RESULTS: Between 6 and 43 base pair exchanges between the HBV genomes of the infants and their mothers were identified. The mutations spread over the entire virus genome. Nucleotide exchanges in the basic core promotor and precore region were identified in all cases. A heterogeneous virus population was detected in four mothers. CONCLUSIONS: Many new mutations were proved to emerge during fulminant hepatitis B in infants, who had been perinatally infected. HBeAg negative variants were the predominant population in all children, whereas these mutants could only be detected as subpopulations in four mothers. The data suggest that the selection of a specific HBeAg negative viral strain may be associated with the development of fulminant hepatitis B in children.

Adult↗
PubMed2004

3D imaging with an isocentric mobile C-arm comparison of image quality with spiral CT.

The purpose of this study was to evaluate the image quality of the new 3D imaging system (ISO-C-3D) for osteosyntheses of tibial condylar fractures in comparison with spiral CT (CT). Sixteen human cadaveric knees were examined with a C-arm 3D imaging system and spiral computed tomography. Various screws and plates of steel and titanium were used for osteosynthesis in these specimens. Image quality and clinical value of multiplanar (MP) reformatting of both methods were analyzed. In addition, five patients with tibial condylar fractures were examined for diagnosis and intra-operative control. The image quality of the C-arm 3D imaging system in the cadaveric study was rated as significantly worse than that of spiral CT with and without prostheses. After implantation of prostheses an increased incidence of artifacts was observed, but the diagnostic accuracy was not affected. Titanium implants caused the smallest number of artifacts. The image quality of ISO-C is inferior to CT, and metal artifacts were more prominent, but the clinical value was equal. ISO-C-3D can be useful in planning operative reconstructions and can verify the reconstruction of articular surfaces and the position of implants with diagnostic image quality.

Artifacts↗