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Biomedical subjects

U Bode

Publications and source records attributed to U Bode.

At least 37 records · Page 2Linked to original sources
PubMed2000

Mutations in the a3 subunit of the vacuolar H(+)-ATPase cause infantile malignant osteopetrosis.

Although the gene defects for several mouse mutants with severe osteopetrosis are known, the genes underlying human infantile malignant recessive osteopetrosis remain elusive. Osteopetrosis is thought to be caused by a defect in osteoclast function. These cells degrade bone material in a tightly sealed extracellular compartment that is acidified by a vacuolar (V)-type H(+)-ATPase. Genes encoding components of the acidification machinery are candidate genes for osteopetrosis. In five of ten patients with infantile malignant osteopetrosis, we now demonstrate five different mutations in OC116, the gene encoding the a3 subunit of the V-ATPase from osteoclasts. Two independent patients were homozygous for mutations that predict a total loss of function by severely truncating the protein. By affecting a splice site, another homozygous mutation deletes 14 amino acids within the N-terminus, which interacts with other subunits of the proton pump. On the other hand, in four patients no mutations were found, and one patient from a consanguineous family did not show homozygosity at the OC116 locus, suggesting that mutations in at least one different gene may underlie osteopetrosis. Our work shows that mutations in the gene encoding the a3 subunit of the proton pump are a rather common cause of infantile osteopetrosis and suggests that this disease is genetically heterogeneous.

Amino Acid Sequence↗
PubMed2000

Primary central nervous system lymphoma: a clinicopathological study of 28 cases.

A group of 28 consecutive patients (mean age 59 years) with primary central nervous system lymphoma (PCNSL) was treated with different regimens, including steroids only, radiotherapy (RT), chemotherapy or combinations of all. Lymphoma was classified as high grade malignant B-cell non-Hodgkin's lymphoma of the diffuse large cell type in each of these cases. RT alone led to tumour remission in more than 70 per cent, survival could be prolonged with additional chemotherapy. Thirteen patients were treated with chemotherapy alone; nine of them received a novel combined intraventricular and systemic polychemotherapy protocol based on high dose methotrexate (MTX) and high dose cytarabine (ara-C). The response rate was 90 per cent with 80 per cent complete responses. Neurotoxicity, i.e. white matter lesions associated with severe cognitive dysfunction affected both patients surviving RT more than a year and patients treated with combination RT/chemotherapy. Confluent white matter hyperintense lesions were detectable on MRI in three out of 13 patients treated with chemotherapy alone, however, cognitive dysfunction has not been detected in these patients.

Adult↗
PubMed2000

[Psychological interventions for acute pain in childhood].

BACKGROUND: Pain sensation depends on individual anxiety and situational circumstances. It is attributed a psychological and social basis. In children, the sensation of pain generally exceeds its perception. ACUTE PAIN IN CHILDHOOD: Facing acute pain in childhood - especially during medical procedures -, interventions derived from behavioural medicine may help minimize the sensation of fear and pain as well as maximize the experience of internal control. But, it is impossible to totally eliminate acute pain that way. Although it is undisputed that children benefit from psychological intervention, in clinical practice its potential is largely underestimated. Factors with impact on the sensation of acute pain and resulting behavioural and coping strategies are presented. The psychological preparation for a painful medical procedure is demonstrated in detail as an example of a behavioural medicine derived procedure.

English Abstract↗
PubMed2000

Structuring psychosocial care in pediatric oncology.

The requirements for high quality psychosocial care for children with cancer and their families are steadily increasing. As an additional supplement to medical and nursing care, psychosocial work has to consider both the requirements of the medical treatment and the associated stress factors. It is essential to structure the different possibilities of intervention in a way which guarantees the practice of psychosocial care within the ongoing medical care. This requires a standardized psychosocial care manual. In July 1994, a 'Manual for Psychological Care in Pediatric Oncology' was put into practice and has been continually improved in the Department of Pediatric Hematology/Oncology of the University of Bonn. It contains special indications for different standards of psychosocial care, is oriented according to the phases and situations of medical treatment, and consists of a health education program as well as special care measurements. The latter are related to both the stressors primarily caused by the requirements of familial adherence to medical and nursing care and the stressors primarily caused by factors of the individual or the familial life circumstances. The theoretical basis of this manual and concrete information for its use are described in this paper.

Child↗
PubMed2000

Procalcitonin in paediatric cancer patients: its diagnostic relevance is superior to that of C-reactive protein, interleukin 6, interleukin 8, soluble interleukin 2 receptor and soluble tumour necrosis factor receptor II.

Sensitive parameters of inflammation are rare in neutropenic cancer patients. In this study, procalcitonin (PCT), C-reactive protein (CRP), interleukin 6 (IL-6), IL-8, the soluble IL-2 receptor (sIL-2R) and the soluble tumour necrosis factor receptor II (sTNFRII) were evaluated for their diagnostic relevance in febrile episodes of cancer patients. Plasma or serum levels of these parameters were determined in neutropenic children with febrile episodes (n = 122) classified according to both the kind of infection [60 cases of fever of unknown origin (FUO), 28 cases of localized infection, 13 cases of pneumonia, 20 cases of bacteraemia, one case of fungaemia] and the World Health Organization (WHO) score of chemotherapy-induced mucositis. At baseline and during the febrile episodes, the highest levels of all parameters were observed in cases of gram-negative bacteraemia. However, in FUO and localized infections, low or only slightly elevated median levels of all parameters were documented. The degree of chemotherapy-induced mucositis did not influence the value of any parameter. In comparison with the other inflammatory parameters, PCT (optimum cut-off level 0.5 microg/l) was a more sensitive and more specific parameter in the diagnosis of high-risk (gram-negative bacteraemia) and low-risk (FUO) episodes, as well as in the sequential assessment of all febrile neutropenic episodes.

Adolescent↗
PubMed2000

Surveillance for nosocomial and central line-related infections among pediatric hematology-oncology patients.

OBJECTIVE: To determine the incidence of all nosocomial infections (NIs) in pediatric hematology-oncology patients, as well as central venous access device (CVAD)-associated infections acquired during home care. DESIGN: Prospective surveillance study. SETTING: The Pediatric Hematology and Oncology Department at the University Hospital Bonn. PATIENTS: All patients admitted from January through October 1998 (surveillance period). METHODS: Standardized surveillance system based on the Centers for Disease Control and Prevention's National Nosocomial Infections Surveillance System. RESULTS: A total of 143 patients were hospitalized for 3,701 days (776 admissions) during the surveillance period. Of the 40 NIs detected, 26 were CVAD-related, with 21 bloodstream infections (BSIs) and 5 local infections. Four were Clostridium difficile-associated diarrheal illnesses, 3 were pneumonias, and 7 were other infections. The incidence of NIs was 10.8 per 1,000 patient-days (5.2 NIs/100 admissions). The overall CVAD-related BSI rate was 7.4 per 1,000 utilization days, without a significant difference between implanted infusion ports and tunneled catheters. In addition, 7 CVAD-related infections occurred during home care. All 8 BSIs associated with tunneled catheters and 13 (76%) of the 17 BSIs associated with ports were acquired nosocomially. For inpatients and outpatients combined, the exit sites of tunneled catheters were more likely to become locally infected than were the needle entry sites of ports (relative risk, 8.0; P=.007). In 30 (75%) of the 40 NIs, the affected patients had severe neutropenia (<500/mm3) at the time of infection. CONCLUSIONS: Most NIs in the pediatric hematology-oncology patients were associated with CVAD devices. Although many infections in this high-risk population may not be preventable through infection control measures, the careful evaluation of specific infection rates permits the identification of risk factors that may be targeted by infection control programs. Prospective surveillance for NIs on pediatric oncology units is an indispensable tool for this internal quality control.

Adolescent↗
PubMed1999

Naive and memory T lymphocytes migrate in comparable numbers through normal rat liver: activated T cells accumulate in the periportal field.

Although the liver is known to contain a significant number of lymphocytes, migration of these through the compartments of the liver, parenchyma and periportal field, has not been studied. The periportal field, in particular, is affected in several immunological disorders of the liver. Populations of labeled naive, activated, and memory T cells were injected into congenic rats. The recipient livers and draining lymph nodes were removed at various time points, and cryostat sections were analyzed for the presence of donor cells using quantitative immunohistology. Donor cell proliferation and apoptosis were examined in vivo by BrdU (5 microM 5-bromo-2-deoxyuridine) incorporation and the TUNEL technique, respectively. Early after injection (0.5-1 h), naive, activated, and memory T cells were localized to the parenchyma and periportal field in comparable numbers. With time, all T cell subsets left the parenchyma but remained or, in the case of activated T cells, significantly accumulated in the periportal field. Furthermore, 12% of activated donor T cells proliferated in vivo within the periportal field, and 0.5% showed evidence of apoptosis. Taken together, not only activated and memory, but also naive T cells continuously migrate through the liver, showing a preference for the periportal field, and activated T cells mainly proliferate there. This may explain why many immunological liver diseases predominantly affect the periportal field.

Animals↗
PubMed1999

Activated T cells enter rat lymph nodes and Peyer's patches via high endothelial venules: survival by tissue-specific proliferation and preferential exit of CD8+ T cell progeny.

Activated T cells reach the lymph nodes via afferent lymphatics but it is unknown to what extent they also enter them directly via high endothelial venules (HEV). Little is known about the mechanism mediating the proliferation of activated T cells within lymphoid tissues in vivo or the subsequent fate of the progeny. Therefore, we stimulated rat T cells via TCR and CD28 in vitro and after injection identified them in the blood and the HEV of lymphoid organs at several time points. In addition, the proliferation of these cells was studied after entering different lymphoid organs. Our results show that, firstly, activated T cells continuously enter lymph nodes and Peyer's patches directly via HEV. Second, they proliferate within lymphoid organs, the rate significantly depending on the microenvironment. Third, mainly CD8+ progeny are able to leave the tissues and re-enter the blood. Thus, the distribution of activated T cells circulating through the body can be regulated during entry, but also within the tissue by influencing their proliferation and subsequent release.

Animals↗
PubMed1999

Homozygous alpha-thalassaemia and hypospadias--common aetiology or incidental association? Long-term survival of Hb Bart's hydrops syndrome leads to new aspects for counselling of alpha-thalassaemic traits.

UNLABELLED: Fetuses with homozygous alpha-thalassaemia develop Hb Bart's hydrops fetalis syndrome, which usually leads either to abortion or fetal/neonatal death. We report diagnosis, intrauterine transfusion therapy, neonatal intensive care management and long-term follow-up of a Vietnamese infant who survived Hb Bart's hydrops fetalis syndrome. During the first 2 years the child had normal development. In addition, the patient exhibited penoscrotal hypospadias. Despite a thorough endocrinological work-up the aetiology of genital ambiguity could not be elucidated. A review of the literature showed an association of homozygous alpha-thalassaemia and hypospadias in all surviving male children, suggesting a common aetiology for both entities. CONCLUSION: On the basis of our findings, we speculate that an unknown gene on chromosome 16 responsible for genital formation is altered in homozygous alpha-thalassaemia.

Chromosomes, Human, Pair 16↗
PubMed1999

Enhanced expression of fas ligand (CD95L) on T cells after segmental allergen provocation in asthma.

BACKGROUND: Little is known about the termination of the T-cell driven inflammation found in patients with allergic asthma. OBJECTIVE: Because signals delivered through Fas/Fas ligand can lead to T-cell apoptosis, we investigated the expression of Fas and Fas ligand on peripheral blood- and bronchoalveolar lavage fluid (BALF)-derived T cells and the percentage of apoptotic BALF cells in asthma. METHODS: Nine atopic subjects with mild asthma and 9 control subjects underwent segmental sham and allergen challenge. Flow cytometry was used to determine the T-cell expression of Fas and Fas ligand, and the terminal dUTP nick end labeled technique was applied to detect apoptotic BALF cells. RESULTS: In asthmatic and control subjects almost all T cells in the BALF expressed Fas antigen without changes after saline or allergen challenge. A small percentage of T cells in BALF expressed the Fas ligand. In asthmatic subjects, but not in control subjects, there was a significant increase in Fas ligand after allergen challenge (CD3: 0.8% +/- 0.6% [baseline] vs 3.2% +/- 1.2% [allergen challenge]; CD4: 1.8% +/- 0.0% vs 4.3% +/- 1.8%; CD8: 2.8% +/- 2.4% vs 9.1% +/- 4.8%) but not after saline challenge, with a significant correlation to the percentage of BALF eosinophils. Apoptotic BALF cells were localized exclusively in macrophages at a very low frequency (0.03% to 0.15%) and without changes after saline or allergen challenge in both groups. CONCLUSION: In asthma there is an upregulation of Fas ligand on T cells in BALF after allergen challenge. Because there is no evidence for increased apoptosis, this phenomenon may reflect antigen-induced T-cell activation rather than apoptosis.

Adult↗
PubMed1999

Distribution of activated T cells migrating through the body: a matter of life and death.

The preferential distribution of lymphocyte subsets in tissues is attributed to a selective lymphocyte-endothelium interaction during entry. However, proliferation and death within the tissue, and exit from the tissue, might also play a role. Here, Jürgen Westermann and Ulrike Bode provide evidence that preferential survival in the tissue of initial stimulation is the major factor in the preferential distribution of activated T cells.

Animals↗
PubMed1999

Conditioned immunosuppression makes subtherapeutic cyclosporin effective via splenic innervation.

The present study investigated the mechanisms by which conditioned immunosuppression enhances the effectiveness of cyclosporin A (CsA) treatment in prolonging heart allograft survival. Dark Agouti rats that were administered subtherapeutic CsA (7 x 2 mg/kg on alternate days) rejected heart allografts at the same time as non-CsA-treated rats. The addition of a behavioral conditioning regimen (conditioned stimulus, saccharin; unconditioned stimulus, 20 mg/kg CsA) to the subtherapeutic CsA protocol produced a significant prolongation of graft survival, including long-term survival (>100 days) in 20% of the animals. Prior sympathetic denervation of the spleen completely blocked this effect. In nontransplanted rats both conditioning and CsA treatment reduce interleukin-2 and interferon (IFN)-gamma in the supernatant of proliferating splenocytes. Additionally, therapeutic CsA treatment decreased the number of IFN-gamma-producing CD4(+) naive and memory T cells in the spleen. In contrast, behavioral conditioning increased that number. These data indicate that behavioral conditioning prolongs heart allograft survival by inhibiting the release of these cytokines in the spleen via sympathetic innervation, supplementing the inhibited cytokine production induced by CsA treatment.

Animals↗
PubMed1999

Accidental iatrogenic intoxications by cytotoxic drugs: error analysis and practical preventive strategies.

OBJECTIVES: Drug errors are quite common. Many of them become harmful only if they remain undetected, ultimately resulting in injury to the patient. Errors with cytotoxic drugs are especially dangerous because of the highly toxic potential of the drugs involved. For medico-legal reasons, only 1 case of accidental iatrogenic intoxication by cytotoxic drugs tends to be investigated at a time, because the focus is placed on individual responsibility rather than on system errors. The aim of our study was to investigate whether accidental iatrogenic intoxications by cytotoxic drugs are faults of either the individual or the system. The statistical analysis of distribution and quality of such errors, and the in-depth analysis of contributing factors delivered a rational basis for the development of practical preventive strategies. METHODS: A total of 134 cases of accidental iatrogenic intoxication by a cytotoxic drug (from literature reports since 1966 identified by an electronic literature survey, as well as our own unpublished cases) underwent a systematic error analysis based on a 2-dimensional model of error generation. Incidents were classified by error characteristics and point in time of occurrence, and their distribution was statistically evaluated. The theories of error research, informatics, sensory physiology, cognitive psychology, occupational medicine and management have helped to classify and depict potential sources of error as well as reveal clues for error prevention. RESULTS: Monocausal errors were the exception. In the majority of cases, a confluence of unfavourable circumstances either brought about the error, or prevented its timely interception. Most cases with a fatal outcome involved erroneous drug administration. Object-inherent factors were the predominant causes. A lack of expert as well as general knowledge was a contributing element. In error detection and prevention of error sequelae, supervision and back-checking are essential. Improvement of both the individual training and work environment, enhanced object identification by manufacturers and hospitals, increased redundancy, proper usage of technical aids, and restructuring of systems are the hallmarks for error prevention. CONCLUSIONS: Errors follow general patterns even in oncology. Complex interdependencies of contributing factors are the rule. Thus, system changes of the working environment are most promising with regard to error prevention. Effective error control involves adapting a set of basic principles to the specific work environment. The work environment should allow for rectification of errors without penalty. Regular and ongoing intra-organisational error analysis needs to be an integral part of any error prevention strategy. However, it seems impossible to totally eliminate errors. Instead, if the environment guarantees timely error interception, most sequelae are avoided, and errors transform into a system-wide learning tool.

Antineoplastic Agents↗
PubMed1998

Regeneration of implanted splenic tissue in the rat: re-innervation is host age-dependent and necessary for tissue development.

The loss of spleen may lead to fatal bacterial infections. To prevent this, splenic autotransplantation has been performed in humans and experimental animals. However, there is still controversy about the protective function of this procedure. Since innervation plays an important role in splenic function, we investigated whether splenic regenerates are re-innervated, and whether this depends on the donor and host age. Splenic tissue (30 mg) was implanted into the greater omentum of either young (2 days) or old (12 months) rats, from either young or old syngeneic animals. After 3 months of regeneration, the weight of the regenerates was determined, PGP+ nerve fibers were revealed by immunohistology, and subdivided into nerve fibers of sympathetic (TH+, NPY+) or sensory (SP+, CGRP+) origin. In addition, proliferating (Ki-67 proliferation antigen+) and apoptotic cells (TUNEL technique+) were likewise investigated. No innervation of splenic regenerates was observed after implantation into old hosts, correlating with poorly developed splenic compartments. In contrast, almost normal re-innervation occurred in young hosts after implantation of both young and old splenic tissue. These regenerates showed well-developed splenic compartments and a normal number and tissue distribution of proliferating and apoptotic cells. However, after the implantation of young tissue, the final size of splenic regenerates was three times larger (140 +/- 30 vs. 40 +/- 10 mg). Thus, re-innervation of splenic implants is necessary for their subsequent development. It is determined by host age, whereas the final size of the splenic regenerates is regulated by donor age-dependent factors. This model is useful for studying both the process leading to initial innervation and the consequences of this innervation.

Aging↗
PubMed1998

IDA-FLAG (idarubicin, fludarabine, cytarabine, G-CSF), an effective remission-induction therapy for poor-prognosis AML of childhood prior to allogeneic or autologous bone marrow transplantation: experiences of a phase II trial.

A phase II trial was designed to explore the potential feasibility and efficacy of a reinduction therapy consisting of fludarabine, cytarabine, idarubicin and granulocyte colony stimulating factor (G-CSF) for acute myelogenous leukaemia (AML) patients with poor prognosis. Twenty-three patients aged 1 2-17.5 years with refractory (n=3), relapsed (n=19) or secondary (n=11) AML were treated with the IDA-FLAG regimen, a combination therapy of idarubicin (days 2-4, 12 mg/m2/d), fludarabine (days 1-4, 30 mg/m2/d), cytarabine (days 1-4, 2000mg/ m2/d) and G-CSF (day 0 up to ANC > 1 x 10(9)/l, 400 microg/m2/ d). They received a total of 3 7 courses of IDA-FLAG and/or FLAG (IDA-FLAG without idarubicin). 17/23 patients achieved a complete remission (CR) with a median duration of 13.5 months (1-39 months), one patient showed a partial remission, and five were nonresponders while in CR, 11 patients underwent bone marrow or PBSC (peripheral blood stem cells) transplantation. Overall, nine patients remain in continuous complete remission with a median duration of 17.5 months (9.5-39 months). The toxicity of the IDA-FLAG courses was more severe than for the FLAG courses with marked neutropenia and thrombocytopenia (for IDA-FLAG: median 22.5 and 25 d respectively; for FLAG: median 10.5 and 14 d respectively). Pulmonary infections were the main nonhaematological toxicity. One patient died in CR from invasive aspergillosis. The IDA-FLAG regimen produced a CR of >12 months in more than half of the patients and can be recommended as a therapeutic option prior to allogeneic or autologous bone marrow transplantation.

Adolescent↗
PubMed1997

CNS late effects after ALL therapy in childhood. Part I: Neuroradiological findings in long-term survivors of childhood ALL--an evaluation of the interferences between morphology and neuropsychological performance. The German Late Effects Working Group.

The effect of cranial irradiation on possible therapy-induced morphological central nervous system (CNS) side effects of children cured from acute lymphoblastic leukemia (ALL) is controversially discussed. In a retrospective multicenter study, 118 former ALL patients in first continuous remission were investigated using cranial computerised tomography (CCT) or magnetic resonance imaging (MRI) scans to evaluate CNS related impairments. Corresponding to the different kinds of CNS prophylaxis, the patient sample was divided: group A (n = 39) receiving intrathecal methotrexate (ITMTX) and systemical medium-high-dose methotrexate (SMHDMTX), group B (n = 41) cranial irradiated (in mean 16.8 Gy) and administering ITMTX and SMHDMTX, group C (n = 38) irradiated (in mean 17.1 Gy) and getting ITMTX. Pathologic scans showed atrophy, leukoencephalopathy, calcifications or grey matter changes. These findings were compared with the neuropsychological test results. Abnormal MRI or CCI scans were found in 61/118 patients (51.7%). Fifteen belonged to group A (38.5%), 23 to B (56.1%) and 23 to C (60.5%). Patients with definite CNS changes show reduced neuropsychological test results. The prevalence of brain alterations seems to appear twice increased after lengthening the posttherapeutic interval in irradiated patients as in nonirradiated patients. Irradiated patients as an age younger than 2 years at diagnosis may show a lower prevalence for developing CNS alterations. CNS alterations are not sex-related. Children treated with cranial irradiation in combination with SMHDMTX and/or ITMTX were at greater risk of developing morphological brain alterations than patients with chemotherapy alone. These alterations are partly correlated with reduced neuropsychological performances and seem to stay with a longer posttherapeutic interval.

Adolescent↗