PubMed Health⌕ Search

Biomedical subjects

E Jaeckel

Publications and source records attributed to E Jaeckel.

15 recordsLinked to original sources
PubMed2005

[Autoimmune polyglandular syndromes].

Autoimmune polyglandular syndromes are rare autoimmune endocrinopathies, which can be also associated with non endocrine autoimmune diseases. The autoimmune polyglandular syndrome type I (autoimmune polyendocrinopathy-candidiasis ectodermal dystrophy; APECED) is distinguished from autoimmune polyglandular syndrome type 2 (APS-2). Main symptoms of APECED are adrenal insufficiency, hypoparathyroidism and candidiasis. The diagnosis is established when two out of three of these symptoms are present. APECED is associated with mutations of the autoimmune regulator gene (AIRE) and predominantly affects juvenile patients with a family background from Sardinia, Finland and Iranian Jews. The APS-2 is not AIRE associated. It is characterized by the presence of autoimmune thyroid disease, adrenal insufficiency and/or diabetes mellitus type I. APS-2 is more common than APECED and mainly affects adult women without any preference of a certain ethnic group. Therapy consists of hormone replacement therapy and treatment of clinical symptoms. In some APECED patients immunosuppressive therapy seems to be promising.

Candidiasis↗
PubMed2004

[Organ transplantation in endocrinology. Islet cells and pancreas].

Pancreas transplantation is a successful and effective procedure resulting in tight glucose control. Due to the postoperative morbidity and the need for immunosuppression pancreas transplantation should be considered at the time of kidney transplantation. Besides this, pancreas transplantation alone should be considered for patients with unacceptably poor metabolic control and quality of life despite optimal medical treatment. Recently, islet transplantation became a less invasive alternative to pancreas transplantation. Due to the lack of long-term follow-up and due to the need of multiple donor grafts for one recipient, islet transplantation should be performed under experimental settings in experienced centers. New developments in protecting transplanted islets and in the induction of donor-specific tolerance could increase the indication to perform the procedure. Therefore alternative sources of beta-cells have to be identified.

Comorbidity↗
PubMed2001

Treatment of acute hepatitis C with interferon alfa-2b.

BACKGROUND: In people who are infected with the hepatitis C virus (HCV) chronic infection often develops and is difficult to eradicate. We sought to determine whether treatment during the acute phase could prevent the development of chronic infection. METHODS: Between 1998 and 2001, we identified 44 patients throughout Germany who had acute hepatitis C. Patients received 5 million U of interferon alfa-2b subcutaneously daily for 4 weeks and then three times per week for another 20 weeks. Serum HCV RNA levels were measured before and during therapy and 24 weeks after the end of therapy. RESULTS: The mean age of the 44 patients was 36 years; 25 were women. Nine became infected with HCV through intravenous drug use, 14 through a needle-stick injury, 7 through medical procedures, and 10 through sexual contact; the mode of infection could not be determined in 4. The average time from infection to the first signs or symptoms of hepatitis was 54 days, and the average time from infection until the start of therapy was 89 days. At the end of both therapy and follow-up, 43 patients (98 percent) had undetectable levels of HCV RNA in serum and normal serum alanine aminotransferase levels. Levels of HCV RNA became undetectable after an average of 3.2 weeks of treatment. Therapy was well tolerated in all but one patient, who stopped therapy after 12 weeks because of side effects. CONCLUSIONS: Treatment of acute hepatitis C with interferon alfa-2b prevents chronic infection.

Acute Disease↗
PubMed2001

Hepatitis C and the leptin system: bound leptin levels are elevated in patients with hepatitis C and decrease during antiviral therapy.

BACKGROUND: Serum leptin levels are elevated in alcoholic liver cirrhosis and thus might be involved in the anorexia and hypermetabolism often seen in those patients. We hypothesized that the leptin system is modulated in patients with hepatitis C and might be affected by antiviral therapy. The aim of this study was to investigate the different leptin components in serum of patients with hepatitis C before, during and after interferon alpha and ribavirin therapy and in controls. METHODS: 25 patients (11 female, 14 male) with chronic hepatitis C were compared with body mass index, gender and age-matched controls (n = 25). Patients were treated with interferon alpha alone (3 MU tiw) or in combination with ribavirin for 6-12 months. Free leptin and bound leptin levels were measured using specific radioimmunoassays before interferon therapy, at 12 weeks of therapy and after 3 months of follow-up. RESULTS: Free leptin levels were higher in female than in male subjects, both for patients (P < 0.01) and controls (P < 0.05). Bound leptin levels were elevated in both female (P < 0.05) and male (P < 0.001) patients compared to controls. No alteration of free leptin levels was found during therapy, whereas bound leptin levels decreased after 3 months of therapy (P < 0.005) and re-increased to the baseline levels 3 months after therapy was stopped. Responder but not non-responder had decreased bound leptin levels (P < 0.01) comparing pre- and posttreatment levels. However, no significant correlations were determined between any of the leptin components to virus load, ALT, TNF alpha receptor levels (sTNFR-75, sTNFR-55) and histopathology at any time point. CONCLUSION: Since no correlation was found between the different leptin components and any of the inflammatory markers, the decrease in bound leptin levels during antiviral therapy suggests either a direct interferon-dependent effect on the leptin system or an alteration of other leptin secretagogues.

Adult↗
PubMed2001

Induction of autoantibodies to the adrenal cortex and pancreatic islet cells by interferon alpha therapy for chronic hepatitis C.

BACKGROUND/AIMS: Interferon alpha (IFN-alpha) therapy for chronic hepatitis C may trigger induction of autoimmunity against several organs. Immune reactions against distinct adrenocortical protein antigens involved in adrenal autoimmune disease have not been reported to date. Therefore, we investigated the development of highly sensitive and specific adrenal autoantibodies in patients with chronic hepatitis C in response to IFN-alpha treatment. In addition, we studied induction of pancreatic islet and thyroid autoantibodies. PATIENTS/METHODS: Sera of 75 patients (42 males, 33 females; mean age 47 (13) years) were analysed before, during, and after IFN-alpha therapy (9-18x10(6) IE/week; mean duration 8.3 (3.5) months). Autoantibodies (Abs) to adrenal 21-hydroxylase (21OH-Abs), and to islet glutamic acid decarboxylase (GAD65-Abs) and protein tyrosine phosphatase (IA2-Abs) were determined by a radiobinding assay using (35)S labelled protein generated by an in vitro translation system. Thyroid antibodies were measured by a commercially available ELISA. RESULTS: Thirteen of 75 patients were initially positive for some of the autoantibodies. During or after IFN-alpha therapy, 3/62 initially negative patients (4.8%) developed 21OH-Abs. GAD65-Abs or IA2-Abs appeared in 5/62 and 1/62 patients, respectively (9.7% in total). In 12/62 patients (19.4%), thyroid specific antibodies appeared. In none of the 21OH-Ab positive subjects was adrenal dysfunction observed, and no patient with islet autoantibodies developed diabetes mellitus or impaired glucose tolerance. CONCLUSIONS: IFN-alpha induces 21OH-Abs in some cases, while islet and thyroid specific autoantibodies are more frequently found. However, our results indicate for the first time that the adrenal cortex also has to be considered as a potential target of IFN-alpha related autoimmunity.

Adrenal Cortex↗
PubMed2000

[The course and therapy of acute hepatitis C viral infection. Is a prevention of its becoming chronic possible?].

Due to the large number of patients chronically infected with hepatitis C virus and not responding to combination therapy with interferon-alfa 2 and ribavirin new therapeutic regimens are required. Early treatment of the viral infection might improve the response, as seen in treatment of HIV infection, thereby preventing progression to chronicity. The article reviews the natural course of an acute HCV infection after different modes of transmission like i.v.-drug abuse, transfusion, needle stick injury and blood products. As there are no good animal models for HCV infection, models of an acute infection with other noncytopathic viruses might improve our understanding of the mechanisms of viral clearance. Results from an acute infection of mice with the lymphocytic chorionmeningitis virus are demonstrating the development of a T-cell tolerance by anergy or deletion of virus specific T-cells as possible mechanisms for the failure of the immune system to clear the virus. These findings are compared to the results of CD4+ and CD8+ T-cell responses in patients with acute HCV infection. Several clinical trials have demonstrated a benefit of an early treatment of HCV infection. Although the natural course of acute HCV is changing during the last few years, even recent trials indicate that progression to chronicity might be prevented by early therapy. The studies show that therapy could be improved by daily dosing, higher single doses of interferon compared and prolongation of therapy up to six month. As most patients with acute HCV infection are rather seen in an outpatient practise than in hospitals cases of acute infections should be collected and treatment protocols be standardized to confirm these results in prospective trials. First results in 21 patients show that viral clearance under therapy was achievable in all of the patients.

Acute Disease↗
PubMed1999

Anti-mitochondrial antibodies and other immunological tests in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) has been classified as an autoimmune disease. It is characterized by a multitude of immune-mediated symptoms and phenomena. Humoral autoimmunity directed against mitochondrial auto-antigens or structures cross-reactive with these proteins represents the basis of one of the most specific tests in any autoimmune disease: the detection of auto-antibodies against pyruvate dehydrogenase. The molecular cloning and expression of antigens of the ketoacid dehydrogenase complex has led to the establishment of highly specific and reliable testing systems for anti-mitochondrial antibodies (AMA). The characterization of specific antinuclear auto-antibodies has contributed to the diagnosis of AMA-negative PBC and is an important marker in overlap syndromes of PBC and other autoimmune liver diseases.

Antibodies, Anti-Idiotypic↗
PubMed1999

No evidence for association between IDDMK(1,2)22, a novel isolated retrovirus, and IDDM.

In the past, endogenous retroviral sequences have been isolated from patients suffering from different kinds of autoimmune diseases. Recently, a full length retroviral genome, termed IDDMK(1,2)22, was isolated from patients with new-onset IDDM. This genome contains a major histocompatibility complex II-dependent superantigen within its envelope gene. The viral sequence was found in ten patients with new-onset IDDM, but not in age-matched control subjects (Conrad et al. [9]). We searched for the presence of this viral genome by nested reverse transcription-polymerase chain reaction (RT-PCR) in a cohort of six patients with new-onset IDDM and six control subjects of the same age. We found all samples to be positive without any differences between patients and control subjects. The same results were obtained with supernatants of activated peripheral blood mononuclear cells. We performed isopycnic ultracentrifugation in sucrose density gradients on all samples and were unable to detect particles of the new virus in any of our samples. However, positive signals were obtained from all pellet fractions. RNase, DNase treatment and nested PCRs without reverse transcription showed that the positive signals were probably derived from intracellular RNA and DNA. In summary, no correlation between a positive nested PCR signal for IDDMK(1,2)22 and diabetes was found indicating that the new sequence represents just an additional member of the human endogenous retrovirus (HERV) family with lack of an exogenous counterpart.

Adult↗
PubMed1998

Muscle fiber type distribution in the normal human levator veli palatini muscle.

OBJECTIVE: This study examined the muscle fiber type distribution within the normal adult levator veli palatini muscle. METHODS: Levator veli palatini muscle tissue was harvested from the palates of 12 (seven female, five male) adult noncleft cadavers. Adjacent sections were stained for adenosine triphosphatase at pH 10.4 or 4.2. After mounting, magnifying, and photographing, Type I versus Type II fiber types were differentiated by the intensity of, or by the inhibition of, staining of matched fibers at each pH level. Type I fibers stained light at pH 10.4 and dark at pH 4.2, while Type II fibers stained light at pH 4.2 and dark at pH 10.4. MAIN OUTCOME MEASURES: The number of fibers counted for each specimen ranged from 60 to 616. The numbers of Type I and Type II stained fibers appearing in each muscle tissue sample were determined and expressed as a percentage of the total number of fibers identified. A few identified fibers could not be labelled as either Type I or Type II. RESULTS: The overall proportion of Type I fibers, averaged across all specimens, was 59.8%. Male specimens had 67.4% Type I fibers and 31.8% Type II fibers, while female specimens had 54.4% Type I fibers and 44.4% Type II fibers. CONCLUSIONS: Observed fiber type distributions were similar to those reported for other articulatory muscles, but differed slightly from previously reported distributions for normal levator veli palatini. The distributions observed in this study provide a baseline against which to relate fiber type data from the levator veli palatini of cleft palates to the functional status of the velopharyngeal mechanism.

Adenosine Triphosphatases↗
PubMed1997

Experience with lamivudine against hepatitis B virus.

After several nucleoside analogues have been tested against chronic hepatitis B virus (HBV) infection with minimal success, lamivudine seems to be a highly effective new therapeutic option. This review focuses on nucleoside metabolism and on the molecular action of lamivudine as well as on results of clinical studies for several indications. We report on results of trials on the use of lamivudine for chronic HBV infection, chronic HBV under immunosuppression and prophylaxis or treatment of HBV reinfection before or after orthotopic liver transplantation. Aspects of combination therapy of different nucleoside analogues as well as on combination of lamivudine with interferon are also highlighted. Although lamivudine seems to be highly effective in most patients at the start of therapy, development of resistance by mutations in the viral polymerase is a significant clinical problem. The mode of resistance development is compared with the situation in HIV infection. Possible cross-resistance with other nucleoside analogues and the perspectives of lamivudine therapy are also considered.

2-Aminopurine↗
PubMedDate not supplied

Liver transplantation and autoimmunity.

Autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) represent good indications for orthotopic liver transplantation (OLT). While there is effective treatment for AIH (steroids with or without azathioprine) and PBC (ursodeoxycholic acid) no such treatment is currently established for PSC. The need of transplantation can be delayed for AIH and PBC with appropriate therapies, while treatment options for PSC are still controversially discussed. Although the time point for liver transplantation can be roughly estimated for AIH by failure of immunosuppressive therapy and for PBC by prognostic models, the prediction of survival in patients with PSC is more difficult, and further complicated by the risk of developing cholangiocellular carcinoma. Long term (5-year) outcome after liver transplantation approaches 80 to 90% for autoimmune liver diseases unless cholangiocellular carcinoma complicates PSC at the time of OLT. The risk of disease recurrence has been recognised for each of these entities although its clinical relevance is controversial and not exactly determined today. As survival after liver transplantation is steadily increasing, recurrent autoimmune liver disease may become a clinical problem in the future. Recently de novo autoimmune hepatitis after liver transplantation has been reported from several transplant centres, although its importance still needs to be established.

Autoimmune Diseases↗