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Biomedical subjects

S Wirth

Publications and source records attributed to S Wirth.

At least 37 records · Page 2Linked to original sources
PubMed1995

[Self-assessment of prescribing behavior of psychotropic drugs for children and adolescence. Results of a survey of established physicians].

All registered general practitioners, pediatricians, and neuropsychiatrists of lower franconia were asked to fill out a questionnaire regarding the ratio of 0-20 year old patients with psychiatric symptoms and their prescribing methods of psychopharmaca. Neuropsychiatrists treated less children and adolescents with psychiatric symptoms than pediatricians or general practitioners. Approximately 50% of the patients with psychiatric symptoms received psychopharmaca. The most frequently prescribed psychopharmaca were neuroleptics and antidepressants, followed by phytopharmaca with various ingredients, which were most frequently prescribed by general practitioners. The average duration of a psychopharmacotherapy was 9 weeks. A great deal of uncertainty regarding the prescription of psychopharmaca to children and adolescents has become evident. Despite the fact that an enuresis can not be diagnosed before the end of the 5th year, it was one of the most frequently treated symptom of the 2-5 year old children. On the other hand, approximately one third of all physicians principally do not treat children and adolescents with psychopharmaca.

Adolescent↗
PubMed1994

Class I-restricted cytotoxic T lymphocytes are directly cytopathic for their target cells in vivo.

Although CD8-positive, class I-restricted CTL play a critical role in viral clearance and immunopathology in many model systems, they have not been shown to directly kill their target cells in vivo at the single cell level. Using a hepatitis B surface Ag transgenic mouse model of class I-restricted, CTL-mediated liver disease, we now demonstrate that CD8-positive, Ld-restricted hepatitis B surface Ag-specific CTL bind and kill their target cells in vivo by triggering them to undergo degenerative cytologic changes compatible with apoptosis. Unexpectedly, the data also indicate that the pathologic consequences of this direct, Ag-specific CTL effect are much less severe than the cytodestructive, Ag-nonspecific inflammatory response that they induce when they are activated by Ag recognition.

Animals↗
PubMed1994

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: a severe fatty acid oxidation disorder.

3-Hydroxyacyl-CoA dehydrogenase deficiency is a newly recognised fatty acid oxidation disorder with a usually fatal outcome. We present a further patient who presented with hypoketotic hypoglycaemia, hepatopathy, secondary carnitine deficiency and increased plasma long-chain acylcarnitines. 3-Hydroxydicarboxylic aciduria was present and the diagnosis confirmed in cultured skin fibroblasts. Our patient is compared with those reported in the literature with respect to clinical symptoms, differential diagnosis and possible therapeutic regimens.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1994

Proinflammatory cytokines in serum of patients with acute cerebral ischemia: kinetics of secretion and relation to the extent of brain damage and outcome of disease.

The release of the proinflammatory cytokines IL-1 beta, IL-6, TNF-alpha and soluble TNF-receptors p55 and p75 in peripheral blood was serially determined in 19 patients with acute cerebral ischemia. Only patients admitted within 4 h following onset of symptoms were studied. In contrast to serum levels of IL-1 beta, TNF-alpha and TNF-receptors, which did not exhibit a significant response, IL-6 showed a significant increase of serum levels already within the first hours following onset of disease and reached a plateau at 10 h until day 3 and returned to baseline by day 7. The increase of levels of this cytokine was significantly (P < 0.05) correlated with increasing volumes of brain lesion and was also significantly (P < 0.005) associated with poor functional and neurological outcome. The increase of levels of IL-6 despite a considerable dilution in peripheral blood shown in this preliminary study suggests an early inflammatory response in ischemic brain lesion.

Activities of Daily Living↗
PubMed1993

Mechanisms of class I restricted immunopathology. A transgenic mouse model of fulminant hepatitis.

The molecular and cellular mechanisms responsible for cytotoxic T lymphocyte (CTL)-induced immunopathology are not well defined. Using a model in which hepatitis B surface antigen (HBsAg)-specific CTL cause an acute necroinflammatory liver disease in HBsAg transgenic mice, we demonstrate that class I-restricted disease pathogenesis is an orderly, multistep process that involves direct as well as indirect consequences of CTL activation. It begins (step 1) almost immediately as a direct antigen-specific CTL-target cell interaction that triggers the HBsAg-positive hepatocyte to undergo programmed cell death (apoptosis). It progresses (step 2) within hours to a focal inflammatory response in which antigen-nonspecific lymphocytes and neutrophils amplify the local cytopathic effect of the CTL. The most destructive pathogenetic function of the CTL, however, is to secrete interferon gamma when they encounter antigen in vivo, thereby activating the intrahepatic macrophage and inducing a delayed-type hypersensitivity response (step 3) that destroys the liver and kills the mouse. We propose that the principles illustrated in this study are generally applicable to other models of class I-restricted, CTL-induced immunopathology, and we suggest that they contribute to the immunopathogenesis of viral hepatitis during hepatitis B virus infection in humans.

Animals↗
PubMed1993

Low level virus replication in infants with vertically transmitted fulminant hepatitis and their anti-HBe positive mothers.

Perinatal transmission of hepatitis B virus (HBV) occurs in about 10%-20% of anti-HBe seropositive mothers. The babies are at risk of developing fulminant hepatitis. In most cases no viral DNA has been detected in the sera of mothers and children by conventional hybridisation techniques. Thus, the aim of our investigation was to demonstrate HBV DNA in three children with liver failure and their anti-HBe positive mothers by more sensitive molecular hybridisation techniques. The babies were healthy at birth and did not receive vaccination. At 3 months of age they developed acute liver failure and died from liver insufficiency. Only in one child serum HBV DNA was detected by dot blot hybridisation, but polymerase chain reaction (PCR)-detectable HBV DNA was present in all sera. The liver specimen was negative for HBV DNA by Southern blot hybridisation, but showed a focal distribution of viral sequences as determined by in situ hybridisation. This finding was confirmed by PCR. Our results prove that chronic anti-HBe positive HBsAg carrier mothers and their babies show a low level virus replication. Fulminant hepatitis is due to vertical transmission of very small amounts of viral DNA, only detectable by most sensitive techniques like PCR and in situ hybridisation. Our findings underline the necessity to vaccinate all babies of HBsAg positive mothers regardless of HBeAg/anti-HBe status.

Adolescent↗
PubMed1993

Interferon alfa-2b therapy in children with chronic hepatitis B.

Twenty nine children (mean age 8.3 years, 18 boys, 11 girls) who had biopsy proved chronic hepatitis B virus infection (HBV) with active viral replication were given a 16 week course of interferon alfa-2b treatment (9 million units (MU)/m2, thrice weekly). Fourteen children (48%) showed persistent loss of HBV-DNA 8 months after the end of treatment; 11 (38%) lost hepatitis B e antigen (HBeAg), and two (7%) hepatitis B surface antigen (HBsAg). Alanine aminotransferase activities returned to normal in 12 children. Those who responded had significantly higher initial transaminase activities than those who did not (p < 0.01) but similar serum HBV-DNA. Results were compared with the natural evolution of the disease in a group of 25 children (mean age 8.3 years) with identical initial mean serum HBV-DNA values, followed up during the same period. Two of these (8%) lost HBeAg and one (4%) HBsAg. The 23 remaining control subjects had no decrease in serum HBV-DNA or in transaminase activities compared with values 1 year earlier. It is concluded that treatment with interferon alfa-2b in children may lead to inhibition of HBV replication similar to that described in adults, and may thus shorten disease evolution. Further studies are necessary to establish the best protocols and to identify those patients who are the most likely to respond to treatment.

Alanine Transaminase↗
PubMed1993

[Drug treatment of 7- to 14-year-old children. Results of a parent survey].

In comparison to other European countries, Germany has by far the highest availability of drugs. Consequently the fear is often expressed that drugs may be over-prescribed even for children and that educational measures or home remedies would often be equally effective. In particular, the issue of inappropriate prescribing of psychotropic drugs for children is often raised, even though epidemiological studies have failed to document such a practice. In a study conducted to obtain comprehensive data about the use of drugs by children, questionnaires were given to parents of children at four schools in Bavaria (2 industrial towns, 2 university towns). This anonymous inquiry was supported by the Ministry of Education and Cultural Affairs. Of the 1750 questionnaires distributed 1189 were evaluated (67.9% response rate). On an average, each child took 3.17 drugs per year, mainly for respiratory infections, fever, pain and gastrointestinal symptoms. Analgesics, nasal preparations, cough medicine, gastrointestinal medications and antibiotics were used frequently and psychotropic drugs only rarely (rank 20). For psychiatric conditions, only one child in 170 was given psychotropic drugs and only one in 108 used sedatives. Overall, drugs and home remedies were used with almost equal frequency (1.23:1). For psychiatric problems, home remedies were used three times more frequently, whereas for other problems drugs predominated. Of the parents who responded were 79.3% satisfied with the prescribed drugs; 9.1% stated that they changed the dosage of the prescribed drugs.

Adolescent↗
PubMed1992

Molecular hybridization techniques in current diagnosis of chronic hepatitis B in childhood.

Following the cloning and sequencing of the hepatitis B virus genome, molecular hybridization techniques have been established to detect hepatitis B virus (HBV) DNA in serum and liver tissue. Analyses can be performed by dot blot, Southern blot and in situ hybridization. HBV DNA is regarded to be the most sensitive marker of viral replication and infectivity which was previously related to the presence of hepatitis B e antigen in serum and hepatitis B core antigen in liver cells. In liver tissue different molecular patterns can be recognized as free viral DNA and integrated sequences. Furthermore, introduction of the polymerase chain reaction allows the detection of very small amounts of viral DNA and has markedly improved diagnostic sensitivity. Thus the study of HBV DNA has become a valuable part of the routine diagnosis in chronic hepatitis B, providing a more reliable evaluation of virus replication and infectivity, and facilitating more precise statements about course and prognosis of the disease.

Child↗
PubMed1992

Use of the polymerase chain reaction to demonstrate hepatitis B virus DNA in serum of children with chronic hepatitis B.

The polymerase chain reaction was used to investigate the presence of hepatitis B virus DNA in sera of 61 children with chronic hepatitis B and negative results on dot blot hybridization tests. Our results demonstrate that most chronic carriers of hepatitis B surface antigen in childhood have hepatitis B virus DNA detectable by polymerase chain reaction in their serum and must be considered infectious.

Adolescent↗
PubMed1992

Detection of hepatitis B virus DNA in the liver of children with chronic hepatitis B by in situ hybridization and its relation to other viral markers.

The aim of the study was to detect hepatitis B virus (HBV) DNA by in situ hybridization (ISH) with a 35S-labeled radioactive probe in frozen liver biopsy tissue sections of 63 hepatitis B virus surface antigen (HBsAg)-positive children. The results were compared to other markers of viral replication. HBV DNA was detected in 48 children. Of the 15 negative cases, four had hepatitis B envelope antigen (HBeAg), 10 anti-HBe, and one neither HBeAg nor anti-HBe. Free HBV DNA in serum and liver was positive in one patient. Forty of the positive children were HBeAg- and six anti-HBe-positive; two were negative for both. Of 45 36 had HBV DNA in serum. In 38 of 47 HBV DNA and in 31 of 42 HBcAg could be detected in the liver. The HBV DNA signals were located mainly over the cytoplasm of hepatocytes. The distribution of HBV DNA in the tissue was classified as homogeneous, inhomogeneous with focal patches, and focal. It is concluded that in situ hybridization is a reliable method for detection of HBV DNA in liver tissue of children with chronic hepatitis B. The technique, which can be applied to small amounts of liver tissue, provides informations about the distribution of replicative viral sequences, complementing laboratory data, liver histochemistry, and histology.

Adolescent↗
PubMed1992

Hepatitis B virus DNA in liver tissue of chronic HBsAg carriers in childhood and its relationship to other viral markers.

The aim of the study was to examine the state of hepatitis B virus (HBV) DNA in liver tissue of 103 children with chronic hepatitis B aged 0.5-18 years to detect free and integrated viral sequences by Southern blot hybridization. HBV DNA was found in 74 patients. Seventy-two were seropositive for hepatitis B e antigen (HBeAg) and two had anti-HBe antibodies. Integrated sequences could be demonstrated in two children. One of them had only integrated HBV DNA and was anti-HBe seropositive. The other one presented both free and integrated viral sequences and developed seroconversion from HBeAg to anti-HBe 5 months after biopsy. In 29 hepatitis B surface antigen (HBsAg) carriers, no HBV DNA could be detected in the liver. Ten were HBeAg and 19 anti-HBe seropositive. HBV DNA in serum was found in 65 of the 74 Southern blot-positive and only in two cases of the Southern blot-negative patients. In conclusion, most of the HBeAg-positive children had free HBV DNA in their liver tissue and all patients with anti-HBe except one were negative. According to our results, HBV DNA integration into the liver cell genome can occur at an early stage of chronic disease but is not a frequent event.

Adolescent↗
PubMed1992

Detection of hepatitis B virus DNA by polymerase chain reaction in serum and liver of children with chronic hepatitis B negative for hepatitis B virus DNA by conventional hybridization tests.

Hepatitis B virus (HBV) DNA was detected by polymerase chain reaction in the serum of 87 and liver tissue of 40 children with chronic hepatitis B, negative for HBV DNA by dot blot and Southern blot hybridization, respectively. In sera HBV DNA could be detected in 73 hepatitis B surface antigen carriers; 14 were hepatitis B e antigen (HBeAg), 56 were anti-HBe-seropositive and 3 had neither HBeAg nor positive anti-HBe. In 14 anti-HBe-positive patients no HBV DNA could be found. Viral sequences in liver tissue were present in 33 specimens; 20 were HBeAg and 13 were anti-HBe-seropositive. All of the 7 negative children had anti-HBe. Our results confirm polymerase chain reaction to be a more sensitive method to detect HBV DNA in the liver compared with conventional hybridization techniques. Every HBeAg-positive carrier as well as the majority of anti-HBe-positive patients show ongoing viral replication. This is of special clinical relevance, because these children must be considered infectious.

Adolescent↗
PubMed1992

[Hepatitis C virus (HCV). Low infection rate in premature and full-term neonates following multiple transfusions].

BACKGROUND: Nearly all cases of non-A, non-B post-transfusion hepatitis are caused by hepatitis C virus (HCV). Data for HCV infection in childhood are limited. METHODS: 262 Children who received poly-transfusion between 1979 and 1983 were re-examined at a mean age of 3.5 years for HCV infection using an first-generation enzyme immunoassay to detect anti-HCV antibodies. RESULTS: 14 of 262 children had positive anti-HCV titers (5.3%), 7 of them showed border line results. In further two patients HCV infection was suspected by clinical means, but initial serology was not available. 6.5 years later, 15 of these 16 children were re-examined at a mean age of 9.8 years. All had normal liver enzymes and positive anti-HCV serology was shown in 3 patients (1%). CONCLUSIONS: This study demonstrates a low incidence of HCV infection after poly-transfusion during neonatal age. The rate of HCV infection may be even higher, if other more specific tests for HCV serology or PCR will be routinely available in the near future.

Child, Preschool↗
PubMed1992

[Hepatitis B virus DNA. Detection with polymerase chain reaction in liver tissue of children with chronic hepatitis B].

BACKGROUND: Detection of hepatitis B virus DNA is a reliable evidence of the presence of the viral agent and its replication. Conventional hybridization techniques are limited to detect about 30,000 virions. With the polymerase chain reaction it became possible to extend the sensitivity by amplification of viral sequences. In our study we intended to test whether viral sequences could be found in liver tissue specimens negative for hepatitis B virus DNA by conventional hybridization techniques. METHODS: Hepatitis B virus DNA was detected by PCR in liver tissue of 37 children with chronic hepatitis B, negative for hepatitis B virus DNA by Southern blot hybridization. PCR was performed in a thermal cycler using Taq-polymerase and oligonucleotide primers within the hepatitis B core region. Hepatitis B virus DNA was visualized by ethidium bromide staining and subsequent Southern blot hybridization. RESULTS: 20 patients were HBeAg- and 17 anti-HBe-seropositive. Viral sequences were present in each of the 20 HBeAg positive HBsAg carriers and in 10 patients with anti-HBe. No hepatitis B virus DNA could be found in 7 children, all of them positive for anti-HBe. CONCLUSIONS: Our results confirm polymerase chain reaction to be a more sensitive method to detect hepatitis B virus DNA in the liver compared with conventional hybridization techniques. Every HBeAg positive carrier as well as the majority of anti-HBe positive patients present viral DNA in their liver. Polymerase chain reaction will be suitable to monitor viral replication in spontaneous course and treated patients.

Adolescent↗
PubMed1992

[Chronic hepatitis B. Treatment in childhood with alpha-interferon].

BACKGROUND: In adults several trials of successful therapy for chronic hepatitis B using alpha-interferon with rates of seroconversion from HBeAg to anti-HBe of 30-40% have been reported. Despite the experiences in children are limited, alpha-interferon seems to be a promising drug in this age group as well. We report on our results in the treatment of chronic hepatitis B virus carrier using the recombination interferon alpha-2b. METHODS: 24 children aged 0.6-16 years with chronic active or chronic persistent hepatitis B were included in the study. 12 children received 9 million units of alpha-interferon/m2 body surface area three times a week during four months. 12 control patients were not treated. The follow-up period was 9-12 months after the beginning of therapy. HBsAg, anti-HBs, anti-HBe and Hepatitis-B-Virus-DNA were assessed during this time on a regular basis. RESULTS: Only seroconversion of HBe-Ag to anti-HBe was considered as response to interferon treatment. During the follow-up period anti-HBe could be detected in 5 (41.6%) of the treated and in one (8.3%) of the untreated children. In one case additional seroconversion of HBsAg to anti-HBs due to virus elimination was observed. In all children a marked reduction of viral replication could be shown. 9 patients cleared Hepatitis-B-Virus-DNA at least for one time during therapy. Alpha-interferon was well tolerated and no severe side effects were observed. CONCLUSION: Our results demonstrate that alpha-interferon can be successfully applied to a considerable number of children with chronic hepatitis B. In patients responding to alpha-interferon usually serum transaminases become normal and infectivity of the disease is markedly reduced. alpha-Interferon treatment should be primarily recommended for children with chronic active inflammation.

Adolescent↗