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U Bode

Publications and source records attributed to U Bode.

At least 55 records · Page 3Linked to original sources
PubMed1997

The fate of activated T cells migrating through the body: rescue from apoptosis in the tissue of origin.

After activation within a lymphoid tissue, T lymphocytes enter the blood, where they circulate and then re-enter many organs. However, they predominantly end up in the tissue of origin, a phenomenon so far thought to be caused by organ-specific homing. We analyzed the fate of T cells from different sources stimulated via the T cell receptor and CD28 and then injected intravenously into rats. Our results showed that preferential proliferation and reduced apoptosis, rather than preferential immigration, were responsible for the accumulation of activated T cells in the tissue of origin, explaining how immune responses can spread from site to site but still be restricted to certain regions. Manipulating the life span of such cells might be a promising approach to influencing immune responses.

Animals↗
PubMed1997

CD4+ T cells of both the naive and the memory phenotype enter rat lymph nodes and Peyer's patches via high endothelial venules: within the tissue their migratory behavior differs.

It is thought that naive T cells predominantly enter lymphoid organs such as lymph nodes (LN) and Peyer's patches (PP) via high endothelial venules (HEV), whereas memory T cells migrate mainly into non-lymphoid organs. However, direct evidence for the existence of these distinct migration pathways in vivo is incomplete, and nothing is known about their migration through the different compartments of lymphoid organs. Such knowledge would be of considerable interest for understanding T cell memory in vivo. In the present study we separated naive and memory CD4+ T cells from the rat thoracic duct according to the expression of the high and low molecular weight isoforms of CD45R, respectively. At various time points after injection into congenic animals, these cells were identified by quantitative immunohistology in HEV, and T and B cell areas of different LN and PP. Three major findings emerged. First, both naive and memory CD4+ T cells enter lymphoid organs via the HEV in comparable numbers. Second, naive and memory CD4+ T cells migrate into the B cell area, although in small numbers and continuously enter established germinal centers (GC) with a bias for memory CD4+ T cells. Third, memory CD4+ T cells migrate faster through the T cell area of lymphoid organs than naive CD4+ T cells. Thus, our study shows that memory CD4+ T cells are not excluded from the HEV route. In addition, "memory" might depend in part on the ability of T cells to specifically enter the B cell area and GC and to screen large quantities of lymphoid tissues in a short time.

Animals↗
PubMed1997

Long-term outcome of hepatitis C virus infection after liver transplantation.

We analyzed the long-term clinical course of 71 patients with RNA-positive hepatitis C virus (HCV) infection after liver transplantation. Patients with reinfection after transplantation for HCV-related liver disease, or de novo infection at transplantation were followed for up to 12 years. Cumulative survival for patients with HCV infection at 2, 5, and 10 years after transplantation was 67%, 62%, and 62%, respectively. It was not significantly different from that in patients transplanted for other nonmalignant diseases without HCV infection. The main factor determining long-term survival was the presence or absence of hepatocellular carcinoma (HCC) at transplantation. The 5-year survival rate for HCV patients with or without HCC was 35% versus 73%, respectively (P < .05). No deaths because of viral hepatitis of the graft were observed. Deaths in the first year after transplantation were caused by infectious complications, cardiovascular problems, or rejection; deaths after more than 12 months were exclusively because of recurrence of HCC. Biochemical and histological evidence of hepatitis was found in the majority of the patients, only 16% had normal alanine aminotransferase (ALT) values throughout. Twenty-two percent of patients complained of symptoms, with hepatitis C being the cause in 82% of these. Two patients lost their HCV-RNA for prolonged, ongoing periods of time. The severity of the posttransplantation hepatitis was unrelated to age, sex, severity of liver disease before transplantation, cold ischemic time of the graft, duration of the operation, transfusions, the number of rejection episodes, or the long-term immunosuppressive regime. Only initial short-term therapy with interleukin 2 (IL2) receptor antibodies adversely influenced inflammatory activity. Viral genotype did not influence the course of the graft hepatitis in our series. Histology showed inflammation in 88% of the biopsies and signs of fibrosis in 24%. Mean ALT values correlated with inflammation but not with fibrosis in the biopsies. Porto-portal bridging was observed in six patients, one patient developed cirrhosis within 2 years after orthotopic liver transplantation (OLT). We conclude that chronic hepatitis develops in the majority of patients with HCV infection after liver transplantation. Carrier states without significant laboratory abnormalities are observed in approximately 16%, biochemical abnormalities without symptoms are seen in 60%, and symptomatic disease develops in a quarter of the patients. The disease course closely resembles that seen in nontransplanted hepatitis C patients. It is generally mild but little over 10% of patients develop signs of fibrosis of the graft during the first decade.

Adolescent↗
PubMed1997

Efficiency and toxicity of ifosfamide, cisplatin and doxorubicin in the treatment of childhood hepatoblastoma. Study Committee of the Cooperative Paediatric Liver Tumour Study HB89 of the German Society for Paediatric Oncology and Haematology.

The Cooperative German Paediatric Liver Tumour Study HB89 was conceived to evaluate the efficiency and toxicity of ifosfamide, cisplatin and doxorubicin (IPA) in children with resectable and non-resectable hepatoblastoma (HB) and to determine late sequelae including tubular nephropathy of tumour treatment. The study also assessed the results of a surgical strategy, which adapts the procedure at the initial operation to the tumour's extension in the liver. The relationship of the tumours' histological differentiation to response to chemotherapy was also examined. Patients with a HB restricted to one liver lobe underwent primary resection. Larger tumours were initially treated with IPA chemotherapy and resected at second-look surgery. All patients received IPA adjuvantly after tumour resection. The IPA regimen consisted of ifosfamide 3.5 g/m2 (over 72 h days 1-3), cisplatin 100 mg/m2 (over 5 days 4-8) and doxorubicin 60 mg/m2 (over 48 h, days 9-10). Median follow-up of survivors was 64 months (range 28-82). Long-term disease-free survival (DFS) was for stage I: 21/21; stage II: 3/6; stage III: 28/38; and stage IV: 2/7 (overall 75%). Severe surgical complications occurred in 15% (4/27) of primary and 21% (8/38) of secondary resections with no lethality. 44/45 stage III/IV HB displayed PR after two IPA courses. Drug resistance developed in 8/12 tumours after four or five chemotherapy courses. Acute toxicity was observed in 34/242 (14%) IPA courses. Late sequelae were found in 7/54 (13%) of survivors, and subclinical renal tubulopathy occurred in 7/41 investigated patients (17%). Despite a more favourable prognosis in pure fetal and predominantly fetal histology, statistical analysis revealed no relationship between tumour differentiation and response to chemotherapy. In conclusion, IPA chemotherapy in combination with delayed surgery was highly effective in the treatment of HB.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

[Fetal plasma erythropoietin concentration during intrauterine transfusion therapy in isoimmunohemolytic anemia due to rhesus incompatibility].

PURPOSE: Prenatal plasma concentrations of erythropoietin in fetuses with Rh disease should contribute information to the clinical course and therapeutic control of this disease. METHOD: Fetal plasma erythropoietin (Epo) and haemoglobin (Hb) concentrations were measured in 145 umbilical venous blood samples of 30 fetuses with Rh disease at 20 to 38 weeks' gestation. RESULTS: Both Epo and Hb concentrations were independent of the gestational age in red blood cell-isoimmunised pregnancies. The Hb concentration correlated significantly with Epo concentration without intrauterine transfusion (IUT) (r = -0.519, p = 0.005) and after IUT (i = -0.212, p = 0.01). A haemoglobin deficit of 3 g/dl at 20 weeks' gestation increased to 6 g/dl at 38 weeks' gestation in spite of IUT (p = -0.354, p < 0.001). CONCLUSION: Even with IUT, Epo concentrations increase with gestational age during these pregnancies. This is due to increasing Hb deficits indicating fetal hypoxia which might be prevented by increasing volumes of transfusion.

Adult↗
PubMed1997

Cyanotic Raynaud's phenomenon with conventional but not with liposomal amphotericin B: three case reports.

Despite its common adverse effects intravenous (i.v.) amphotericin B is an indispensable antifungal drug in childhood oncology. We report here on three cases of painful cyanotic Raynaud's phenomenon after i.v. administration or inhalation of amphotericin B. A liposomal i.v. preparation of amphotericin B was well tolerated by the infants. Spasms of peripheral vessels mediated by thromboxane A2 could be responsible for the Raynaud's phenomenon. Hence, inhibitors of prostaglandin synthesis are suggested for therapy.

Administration, Inhalation↗
PubMed1997

[Psychology of patient management: evaluation and quality assurance of psychosocial management in pediatric oncology].

Since the introduction of health-care reform in Germany, quality assurance of inpatient care is required. In paediatric oncology this also includes quality assurance measures of psycho-social care. Care Psychology deals with the development, testing and continual improvement of high-quality psycho-social care. Based on clinical experience, scientific knowledge and ascertained requirements a handbook and manual of service delivery of psycho-social care is formulated and tested in everyday practice. Service performance analyses are carried out, and verified improvements are re-tested in practice. This, as well as additional attempts, should lead to total quality management (TQM) of psycho-social care in paediatric oncology according to the criteria of the European Foundation of Quality Management (EFQM).

Adaptation, Psychological↗
PubMed1996

Famciclovir treatment of hepatitis B virus recurrence after liver transplantation: a pilot study.

Despite hepatitis B immunoprophylaxis hepatitis B virus (HBV) recurrence is a frequent and often fatal complication after orthotopic liver transplantation (OLT). The purine nucleoside analogues penciclovir and its oral form famciclovir (FCV) proved to be well tolerated and effective against herpes simplex and zoster virus infections. In addition, an effective reduction of duck and human HBV replication was observed. Therefore, we conducted an uncontrolled pilot study of famciclovir in patients with HBV recurrence after OLT. Twelve patients have received famciclovir for at least 3 months in an open compassionate-use protocol. FCV was administered orally 500 mg three times a day for all patients (except one patient who was started on 750 mg three times a day for the first 2 weeks). Immediately after starting famciclovir, serum HBV DNA levels declined in 9 of 12 patients (75%) with a mean reduction from baseline levels of 80% after 3 months, 90% after 6 months, and > 95% after 12 months of treatment. With continued treatment, 5 of these 9 patients became negative by conventional hybridization assay, and in one of these HBV DNA became undetectable by polymerase chain reaction (PCR) 28 weeks after the start of treatment. Three patients showed no (sustained) reduction in HBV DNA after at least 3 months of treatment; therefore, FCV was stopped. Latest serum alanine aminotransferase (ALT) levels decreased in 6 of 12 patients (50%) with a median decrease of 80% (range, 40%-95%) in comparison to pretreatment ALT values. ALT levels normalized in 4 patients (33%). One patient died due to sepsis and peritonitis in week 13 of treatment. This event was not related to FCV. No clinically significant side effects were noticed in any patient. The oral nucleoside analog famciclovir reduces HBV replication and transaminase levels in patients with HBV recurrence after liver transplantation. Because long-term FCV treatment is well tolerated, famciclovir appears to be a promising antiviral strategy in the treatment of HBV in immunocompromised patients.

2-Aminopurine↗
PubMed1996

Human papillomavirus is associated with the frequent detection of warty and basaloid high-grade neoplasia of the vulva and cervical neoplasia among immunocompromised women.

A total of 158 women who either HIV-infected or under iatrogenic immunosuppression were examined regularly during a 4-year period to evaluate if certain vulvar neoplasms and cervical neoplasia have similar associated risk factors. Patients with CIN were matched prospectively with immunocompetent controls with CIN. Forty-eight cervical lesions were detected among patients, including 2 invasive carcinoma and 15 CIN-3 lesions, compared to 11 vulvar lesions, including 2 invasive carcinoma and 7 VIN-3 lesions. Women who have more than five life-time partners were more likely to have HPV-DNA positive cervical swabs and vulvar scrapes as well as cervical and/or vulvar neoplasia. Compared to 2.7% of controls 15.2% of patients with CIN had coexisting high-grade lesions of the vulva. With 1 exception all patients with vulvar neoplasia either suffered from symptomatic immunodeficiency or received immunosuppressive drugs for more than 10 years. Except for 1 VIN-3 lesions, all vulvar neoplasms were associated with HPV-DNA types 16, 31, and/or 33. Six of nine patients as well as the 2 controls with coexisting vulvar and cervical neoplasia had the same HPV-type associated with both lesions. All vulvar lesions were classified as either "warty" or "basaloid". In conclusion cervical and bowenoid/basaloid vulvar neoplasia seem to have a similar HPV-related genesis. Malfunction of the cellular immune response appears to be a cofactor in the genesis of HPV-associated neoplasia at both sites.

Case-Control Studies↗
PubMed1995

Complete resection before development of drug resistance is essential for survival from advanced hepatoblastoma--a report from the German Cooperative Pediatric Liver Tumor Study HB-89.

Clinical data and tumor histology of 37 patients with advanced and/or metastatic hepatoblastoma (32 stage III and 5 stage IV) treated according to the protocol of the German Cooperative Pediatric Liver Tumor Study HB-89 from 1988 to 1992 were studied for prognostic factors. Twenty-three patients (73%) were free of tumor 9 months to 5 years (median, 36 months) after treatment, whereas 4 experienced progressive disease, 7 had local relapse, and 3 had recurrent metastases. None of 2 patients with primary lymph node involvement or 5 with primary metastases remained disease-free. Chemotherapy with ifosfamide, cisplatin, and adriamycin was effective in reduction of tumor to resectability in 33 (89%) patients. Drug resistance developed in 6 of 11 patients treated with four or more courses of chemotherapy as could be shown by monitoring of serum-alpha-fetoprotein (AFP) and serial investigations of tumor expansion with sonography and computed tomographic (CT) scan. Only 1 of these patients survived after a liver transplantation. Completeness of tumor resection at second- or third-look laparotomy was significantly related to disease-free survival (P < .0001). Patients with initial serum-AFP values < 100 ng/mL or > 1,000,000 ng/mL had a worse outcome than those with immediate levels (P = .044). The rate of decrease of serum-AFP during chemotherapy was significantly related to prognosis (P = .003). Growth pattern of tumor within the liver (ie, defined nodes versus diffusely disseminated) (P = .011) and vascular tumor invasion (P = .026) were valuable prognostic factors, whereas tumor volume, local infiltration of surrounding tissue, histological subtypes, and epithelial differentiation were not significantly related to the outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Cellular immunodeficiency enhances the progression of human papillomavirus-associated cervical lesions.

Most cases of low-grade cervical intraepithelial neoplasia (CIN) associated with oncogenic human papillomavirus (HPV) types regress spontaneously within years. Unknown co-factors seem to be necessary for a progression to malignancy. To determine the possible role of cellular immunodeficiency as such a co-factor in the genesis of genital neoplasia, 48 HIV-infected women and 52 allograft recipients were examined periodically during a 3-year period. Colposcopy, cytology and HPV-DNA typing (ViraType) were performed at each visit. Each cervical lesion was matched prospectively with 2 lesions from immunocompetent controls. In all, 29/100 patients suffered from cervical neoplasms, including 2 advanced cervical cancers and 9 CIN3 lesions. Correlation between grade of lesion and HPV DNA 16/18 was significant. Low-grade lesions among patients progressed more often than among controls and recurrent lesions after destructive treatment were seen more frequently among patients than among controls. All patients with CD4-lymphocyte counts of < 400/microliters or immunosuppression for more than 3 years suffered from progressive lesions. We conclude that malfunction of the cellular immune response following either HIV-induced depletion or iatrogenic inhibition of CD4-lymphocyte activation, enhances the progression of HPV-induced cervical lesions to malignancy.

CD4-Positive T-Lymphocytes↗
PubMed1994

Methotrexate pharmacokinetics and prognosis in osteosarcoma.

PURPOSE: The influence of methotrexate (MTX) pharmacokinetic parameters on the efficacy of high-dose MTX (HDMTX) in osteosarcoma was analyzed. PATIENTS AND METHODS: MTX serum peak values from 198 patients in 1,703 treatment courses and more detailed pharmacokinetic data from 185 patients in 1,045 treatment courses from the Cooperative Osteosarcoma Study Group (COSS) studies COSS-80, COSS-82, and COSS-86 were investigated. RESULTS: A mean threshold peak level of > or = 1,000 mumol/L for the repeated MTX courses of individual patients was found to correlate significantly to prognosis in study COSS-80 (18% v 64% actuarial 10-year disease-free survival [DFS], P = .0001). Six courses of HDMTX per patient who achieved peak values > or = 1,000 mumol/L were found to be sufficient for a full effect to be seen in DFS in COSS-80. The MTX peak level was found to correlate closely to the area under the curve (AUC). However, AUC was a less powerful determinator of prognosis than the mean threshold MTX peak value. In patients who received cisplatin (DDP) as one of the additional drugs to MTX, the peak values and AUC were significantly increased (1,396 v 1,276 mumol/L, P = .011; 6,684 v 5,820 h.mumol/L, P < or = .002) and only a few patients (6%) did not achieve mean threshold MTX peak values. In addition, following restriction of hydration fluid after the MTX infusion from 4.5 to 3.0 L/m2 per 24 hours, the early MTX half-life (t1/2) and the AUC, but not the MTX peak value, were significantly increased (3.4 v 3.05 hours, and 6,760 v 5,998 h.mumol/L, respectively, P < or = .002). CONCLUSION: MTX pharmacokinetics significantly influence the efficacy of MTX in osteosarcoma. Individual adaptation of the MTX dose to ensure a threshold peak serum level > or = 1,000 mumol/L does not seem necessary at a fixed dose of 12 g MTX/m2, restriction of hydration fluid to 3 L/m2 per 24 hours, and concomitant use of DDP within the drug regimen.

Actuarial Analysis↗
PubMed1994

[Differences in current state and at the beginning of cancer therapy and possible sequelae: a pilot study in pediatric oncology].

The psycho-social and medical care of families with a cancer sick child can be more effective if the team can identify those parents who need help most desperately from the very beginning. In a retrospective study of 20 patients and their families two groups of parents with different levels of stress could be seperated. Highly stressed parents demonstrated already at the time of diagnosis unfavorable coping strategies with the possibility of a cancer disease. They experience a high degree of guilt feelings and believe that they might be responsible for the occurrence of the disease. However they refuse more often than the other parents psycho-social help offered by the professionals. The results suggest to implement special kind of help for the more stressed families already in the early phase of diagnosis and treatment.

Adaptation, Psychological↗
PubMed1993

[Inpatient psychological management in pediatric oncology: the concept of liaison management].

Concepts for counseling and long term support have been the major interest in the psychosocial care of pediatric oncology patients and their families. Similar methods for psychosocial care on the ward are still rare. This paper presents the psychological care of the oncology patients during their stay on the ward, complimentary to the medical treatment. The concept is based on the process of coping with the phases and specific situations (L.P.; B.M.A.; diagnosis; medication ect.) of the cancer therapy. This process contains on the part of the patients and their parents the need for information, active involvement in treatment regimes and relaxation (before, during and after the stressful situation). The concepts of informed consent, adherence and recovery-counseling are related to the coping methods of the patients and their parents. The aims of our concept are to create and utilize diagnostic tests and psychological methods to enable the families to help themselves. To reach this goal, the technique of semantic and pragmatic information is very important because this kind of social communication helps us to make the medical implications of the treatment understandable and suitable for the patients and families.

Adaptation, Psychological↗
PubMed1992

Present status of kidney transplantation.

Kidney transplantation today is the method of choice to treat end-stage renal disease (ESRD) in more than 50% of the ESRD-population. Due to major improvements in surgical handling, immunosuppressive therapy, and infection control, the one-year survival for patients and first grafts has reached nearly 90% in the recent years. In contrast no comparable achievements have been made in long-term graft survival. A constant number of grafts is lost yearly after the first postoperative year. In addition an increasing number of well functioning grafts is lost due to the death of the recipients caused mainly by cardiovascular and malignant disorders. The extension of kidney transplantation to all suitable recipients is nearly exclusively hampered by the organ shortage, which is further enhanced by failing grafts. This urges us to further improve the prognosis for patient and graft. This must include organ sharing on the basis of improved HLA-typing to achieve highly compatible grafts. The tools for differential diagnosis of acute and chronic graft dysfunction have to be improved. New immunosuppressive agents with higher immunosuppressive power and specificity but fewer nephrotoxic, metabolic and hemodynamic side effects are required at least for chronic rejection. The risk of infectious and malignant complications must be limited.

Cadaver↗