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Biomedical subjects

U Bode

Publications and source records attributed to U Bode.

At least 19 recordsLinked to original sources
PubMed2006

[Human Metapneumovirus in hospitalized children - a review].

The human Metapneumovirus (HMPV) has been discovered by von den Hoogen et al. in 2001 and seems to play an important role as etiologic agent in childhood respiratory tract infections in particular involving infants after the 6th month of life and toddlers. Duly considering the hitherto published studies and retrospective analysis of two HMPV seasons (2002-2004) at our institution this review focuses on children, who had to be hospitalized due to HMPV infection. The analysis confirmed, that among those patients there is a high proportion of children with pre-existing risk factors for a complicated clinical course, a high proportion of children with bronchiolitis or pneumonia and a relevant proportion of children with HMPV related apnoeas, most prevalent in the prematurely born. Although the first HMPV infection takes place somewhat later in infancy, the data do not show that HMPV infection is in general milder than RSV infection in hospitalized children. Clinical symptoms and radiological signs do not permit tentative conclusions on the causative agent. This underlines the necessity of specific diagnostic efforts (in case of HMPV with PCR). HMPV may cause lobar or segmental pneumonias difficult to distinguish from bacterial lower respiratory tract infection. Children admitted to the hospital with an acute exacerbation of asthma bronchiale or cystic fibrosis should not only be tested for RSV but also for HMPV. Prospective studies investigating specific therapeutic interventions or describing the impact and prevention of nosocomial HMPV in fection are awaited for. There has been one report of a meningoencephalitis possibly related to HMPV. Thus, liquor samples in such cases should be tested for HMPV too.

Child, Preschool↗
PubMed2006

Influence of prolonged use of intravenous administration sets in paediatric cancer patients on CVAD-related bloodstream infection rates and hospital resources.

BACKGROUND: To assess the effects of extending the routine intravenous administration set (IVAS) change-interval from 72 h (group 1) to 7 days (group 2) on the incidence density for central venous access device (CVAD)-related bloodstream infections (BSIs) and on resource expenditures in a singlecentre pilot study. PROCEDURE: Prospective pre-/post-intervention comparison of two consecutive 12-month surveillance periods (2001-2003) in a 17-bed paediatric oncology tertiary care unit. IVAS changes and nosocomial infections (NIs) were prospectively analysed using a standardized unit-based surveillance system (Oncopaed NI). RESULTS: All 175 eligible patients were enrolled, 96 in group 1 and 79 in group 2. Both groups had similar distributions of primary diagnoses and risk factors. The proportion of IVAS changes performed after 3 days increased from 5.6% to 22.5%, but only 8% of IVASs in group 2 were changed after 7 days. Most IVAS changes (64.8% in group 1 and 92.9% in group 2) were done because of therapeutic interventions (blood products, parenteral nutrition [TNP]) before the scheduled endpoint. Overall, the rates and incidence densities of NIs were significantly lower during the second period. The corresponding results for CVAD-related BSIs did not show significant differences. No death attributable to a NI occurred. The '7-day' strategy resulted in cost savings for devices (3,300 dollars/year) and of nursing time (23 working days/year). CONCLUSIONS: Extending the routine IVAS change-interval from 3 days to 7 days appears to be safe and cost-effective in a paediatric oncology unit with high infection control standards and continuous surveillance for NIs. These results do not prove that 7-day intervals prevent infections, but they do suggest that this policy probably is not harmful and that a prospectively randomized study with sufficient power is needed.

Adolescent↗
PubMed2006

Diagnosis and treatment of catheter-related infections in paediatric oncology: an update.

Otherwise unexplained clinical signs of infection in patients with long-term tunnelled or totally implanted central venous access devices (CVADs) are suspected to be CVAD-associated. Diagnostic methods include catheter swabs, blood cultures and cultures of the catheter tip or port reservoir. In the case of a suspected CVAD-related bloodstream infection in paediatric oncology patients, in-situ treatment without prompt removal of the device can be attempted. Removal of the CVAD should be considered if bacteraemia persists or relapses > or = 72 h after the initiation of (in-vitro effective) antibacterial therapy administered through the line. Timely removal of the device is also recommended if the patient suffers from a complicated infection, or if Staphylococcus aureus, Pseudomonas aeruginosa, multiresistant Acinetobacter baumannii or Candida spp. are isolated from blood cultures. Duration of therapy depends on the immunological recovery of the patient, the pathogen isolated and the presence of related complications, such as thrombosis, pneumonia, endocarditis and osteomyelitis. Antibiotic lock techniques in addition to systemic treatment are beneficial for Gram-positive infections. Although prospectively controlled studies are lacking, the concomitant use of urokinase locks and taurolidine secondary prophylaxis seem to favour catheter salvage.

Acridine Orange↗
PubMed2005

Carboxypeptidase G2 rescue in patients with methotrexate intoxication and renal failure.

The methotrexate (MTX) rescue agent carboxypeptidase G2 (CPDG2) rapidly hydrolyses MTX to the inactive metabolite DAMPA (4-[[2,4-diamino-6-(pteridinyl)methyl]-methylamino]-benzoic acid) and glutamate in patients with MTX-induced renal failure and delayed MTX excretion. DAMPA is thought to be an inactive metabolite of MTX because it is not an effective inhibitor of the MTX target enzyme dihydrofolate reductase. DAMPA is eliminated more rapidly than MTX in these patients, which suggests a nonrenal route of elimination. In a phase II study (May 1997-March 2002), CPDG2 was administered intravenously to 82 patients at a median dose of 50 U kg(-1) (range 33-60 U kg(-1)). Eligible patients for this study had serum MTX concentrations of >10 microM at 36 h or >5 microM at 42 h after start of MTX infusion and documented renal failure (serum creatinine > or =1.5 times the upper limit of normal). Immediately before CPDG2 administration, a median MTX serum level of 11.93 microM (range 0.52-901 microM) was documented. Carboxypeptidase G2 was given at a median of 52 h (range 25-178 h) following the start of an MTX infusion of 1-12 g m(-2) 4-36 h(-1) and resulted in a rapid 97% (range 73-99%) reduction of the MTX serum level. Toxicity related to CPDG2 was not observed. Toxicity related to MTX was documented in about half the patients; four patients died despite CPDG2 administration due to severe myelosuppression and septic complications. In conclusion, administration of CPDG2 is a well-tolerated, safe and a very effective way of MTX elimination in delayed excretion due to renal failure.

Acute Kidney Injury↗
PubMed2004

Oncological management of pediatric cancer patients belonging to Jehovah's Witnesses: a two-institutional experience report.

OBJECTIVES: Aim of this study was to analyze the feasibility of oncological treatment in pediatric patients belonging to Jehovah's Witnesses and to describe the changing policy in performing transfusions and supportive care measures at two German pediatric cancer institutions. PATIENTS AND METHODS: Over a period of 16 years 21 treatments according to the current cooperative protocols were performed in 14 children of Jehovah's Witnesses. Various hematological supportive care measures such as supplementation with iron, human erythropoietin, interleukin 11, granulocyte colony-stimulating factor and autologous or allogeneic stem cell rescue had been applied. For comparison matched pairs treated in our hospitals not belonging to Jehovah's Witnesses and 50 pediatric and adult oncological patients belonging to Jehovah's Witnesses reviewed from the international literature were analyzed with respect to transfusions and outcome. RESULTS: So far, 9 of 14 children are surviving 16-195 months (median 26 months). During the primary therapy they received markedly less transfusions than the control cohort (-39,1% red blood cell transfusions and -37,5% platelet transfusions). The review of 50 reported cases showed that oncological therapy can also be successfully performed with a restricted transfusion regimen in children and particularly in adults. CONCLUSION: Pediatric cancer patients belonging to Jehovah's Witnesses can be treated similarly to other patients. A restrictive transfusion policy and the broad application of hematopoietic supportive care measures may reduce transfusions. This treatment policy and a continuous collaboration with the Hospital Liaison Committee for Jehovah's Witnesses appears to create an oncological treatment situation with a high compliance of patients and parents where court orders may not be necessary.

Blood Loss, Surgical↗
PubMed2002

Pancreatic toxicity after liposomal amphotericin B.

Though liposomal amphotericin B has been available in Germany since 1992, efficacy and safety of this formulation of amphotericin B are still not well-documented in children. As far as gastrointestinal side-effects are concerned, an elevated alkaline phosphatase and elevated transaminases have been reported. In our department, liposomal amphotericin B had been used since 1994 to treat patients with proven or suspected fungal infections in a daily dose of 1-3 mg kg-1. Additionally, patients with high-dose chemotherapy and autologous stem cell support received liposomal amphotericin B prophylactically in a dose of 1 mg kg(-1) three times per week. We performed a retrospective analysis of all 31 patients who had received liposomal amphotericin B by 1999. In five patients, an isolated transient elevation of the serum lipase level during, or shortly after, the therapy with liposomal amphotericin B was detected. Three of these patients showed clinical signs of pancreatitis, with one patient displaying slightly elevated transaminases. So far, elevated levels of serum lipase have not been described as a possible side-effect of a liposomal amphotericin B therapy. The pathogenesis of this elevation is unclear. As possible reasons, an enzyme induction due to fat overload or a toxic damage of the pancreatic tissue by the liposomes or amphotericin B itself are discussed.

Adolescent↗
PubMed2001

Feasibility of intraventricular administration of etoposide in patients with metastatic brain tumours.

As the systemic administration of etoposide is effective in the treatment of relapsed and metastatic brain tumours, a pilot trial was designed to study the feasibility of intraventricular administration of etoposide in such patients. 14 patients aged 2.1 to 33.2 years were treated with intraventricular etoposide simultaneously with either oral or intravenous chemotherapy with trofosfamide or carboplatin and etoposide. In 59 courses (1-12/patient) 0.5 mg etoposide was administered daily via an indwelling subcutaneous reservoir for 5 consecutive days every 2-5 weeks over a period of 0-11 months. During 15 courses in 5 patients serial CSF samples were obtained and etoposide levels were determined by reversed-phase HPLC. Side effects included transient headache and bacterial meningitis, each during 2 courses. Pharmacokinetic data analysis in the CSF (11 courses, 4 patients) revealed a terminal half-life of 7.4+/-1.2 hours and an AUC of 25.0 +/- 9.5 microg h ml(-1)(mean +/- standard deviation). The volume of distribution at steady state and total clearance exhibited a large interindividual variability with mean values of 0.16 l and 0.46 ml min(-1)respectively. Intraventricularly administered etoposide is well tolerated. CSF peak levels exceed more than 100-fold those achieved with intravenous infusions. Further studies should be focused on optimizing the dose and schedule and on determining the effectiveness of intraventricularly administered etoposide.

Adolescent↗
PubMed2001

Gut-derived effector T cells circulating in the blood of the rat: preferential re-distribution by TGFbeta-1 and IL-4 maintained proliferation.

Effector T cells generated in mesenteric lymph nodes (mLN) preferentially accumulate in mLN and sites drained by them, such as Peyer's patches and the lamina propria of the gut, after circulation in the blood. The molecular mechanisms mediating this re-distribution are poorly understood. To study this, rat T cells from mLN were activated via the T cell receptor and CD28, and injected either intravenously into congenic recipients, or maintained in culture in the presence of various cytokines. Three days later effector T cells were identified in vivo and in vitro, and surface molecule expression and proliferation rate was determined. The data show that in vivo effector mLN T cells express significantly higher levels of activation markers and maintain a higher proliferation rate after entering the mLN environment (tissue of origin) than after entering the peripheral LN environment (unrelated site). The proliferation is mediated by TGFbeta-1 and IL-4 present in mLN. The requirement for these cytokines is imprinted on effector mLN T cells during the initial activation. Thus, the preferential proliferation of effector mLN T cells in milieus providing the cytokine mixture experienced during activation ensures a privileged accumulation at sites where they are most needed. This can be used to manipulate the effector phase of an immune response.

Animals↗
PubMed2001

Piperacillin, beta-lactam inhibitor plus gentamicin as empirical therapy of a sequential regimen in febrile neutropenia of pediatric cancer patients.

The beta-lactam/beta-lactamase inhibitor combinations are a good choice for empirical antimicrobial therapy in febrile neutropenic patients, because their antibacterial spectra include both gram-negative and gram-positive pathogens. This trial was initiated to assess the efficacy and safety of piperacillin with the beta-lactam inhibitors sulbactam (PSG group) or tazobactam (PTG group) and gentamicin as initial therapy in febrile neutropenia of pediatric patients. In a prospective study, 239 episodes of fever and neutropenia were analyzed for the clinical and microbiological response dependent on infection etiology and treatment group: 66.5% of episodes were classified as fever of unknown origin (FUO) and 33.5%, as microbiologically or clinically documented infections; 19.2% of all episodes were due to bacteremia, predominantly caused by gram-positive organisms (69.6%). The response to the initial therapy was 55.2% overall and 65.4% in episodes of FUO with a significant higher success rate in the PSG group than in the PTG group (70.1% vs. 52.4%, P=0.039), and 35.0% in documented infections. In episodes with documented infection longer duration of fever and antimicrobial therapy was recorded than for FUO episodes. Four patients died of causes related to infection. Fever relapse occurred in 26 episodes (11.1%), predominantly in patients who were still neutropenic. Toxic side effects were minimal. The initial therapy of piperacillin with sulbactam or tazobactam in combination with gentamicin is well tolerated, and its efficacy is comparable to that of other combination therapies or of monotherapy with beta-lactam antibiotics in pediatric neutropenic cancer patients.

Adolescent↗
PubMed2001

Migration of naive, effector and memory T cells: implications for the regulation of immune responses.

T cells play an important role in protective immune responses and in the pathogenesis of many diseases. Understanding the mechanisms regulating their distribution in vivo may therefore be of therapeutic value. Reviewing studies that have followed the migration of labelled naive, effector and memory T cells in healthy animals reveals that all T-cell subsets enter all organs investigated. Within the tissue, two principally different migration patterns can be identified. First, naive and memory T cells accumulate in lymphoid organs for about 48 h after injection, as the time needed for migration through lymphoid organs is longer than through non-lymphoid organs. During this time, surface molecule expression is temporarily modified. These changes are reversed before leaving the lymphoid organs and entering the blood to start a new cycle of migration. Second, effector T cells are evenly distributed throughout the body, and most die in the tissues within 24 h. However, depending on the presence of cytokines, some are able to survive and to proliferate, and thereby accumulate in defined microenvironments of the body. Analysing the principles regulating T-cell migration and survival within the tissue may lead to the development of new options for the treatment of disease.

Animals↗
PubMed2001

Recent thymic emigrants (CD4+) continuously migrate through lymphoid organs: within the tissue they alter surface molecule expression.

T-cell progenitors migrate from bone marrow (BM) into the thymus. After maturation they are released as recent thymic emigrants (RTE) into the periphery ensuring the diversification of the T-cell repertoire. Both the kinetics with which RTE migrate through the periphery and the surface molecules they express are still unclear. In 1- and 18-month-old Lewis rats CD4+ RTE were identified in blood, spleen, lymph node, and thoracic duct lymph by flow cytometry (CD45RC- and CD90+), were differentiated from CD4+ naive (CD45RC+) and memory T cells (CD45RC-CD90-), and were characterized regarding the expression of surface molecules. Both in 1- and 18-month-old animals the percentage of RTE among the CD4+ population in blood was comparable to that in all other compartments. Surprisingly, RTE expressed alpha4-integrin, LFA-1, and interleukin (IL)-2 receptor at a significantly higher level than naive T cells and more comparable to memory T cells. Within lymphoid tissues RTE, naive, and memory T cells significantly upregulated the expression of CD44 and ICAM-1, and downregulated the expression of L-selectin. These changes were reversed before the cells re-entered the blood. Thus, our data indicate that CD4+ RTE travel through the periphery of young and old rats like mature T cells, continuously modulating their surface molecule expression.

Animals↗
PubMed2001

Meropenem versus ceftazidime as empirical monotherapy in febrile neutropenia of paediatric patients with cancer.

This trial assessed the efficacy and safety of meropenem versus ceftazidime as empirical monotherapy for febrile neutropenia in paediatric cancer patients. In a prospective randomized study, 172 evaluable febrile episodes in the meropenem arm and 170 episodes in the ceftazidime arm were analysed for the clinical and microbiological response dependent on the kind of infection. About half the episodes were classified as fever of unknown origin (FUO) and the remainder as microbiologically or clinically documented infections. The most frequently documented infections in both arms were bacteraemias (22.1 versus 26.5%), predominantly caused by Gram-positive organisms (57.9 versus 71.1%). The success rate of the initial monotherapy differed significantly between the two arms and was 55.8% in the meropenem and 40.0% in the ceftazidime arm (P = 0.003). In addition, a significantly longer duration of fever and of antimicrobial therapy was observed in the ceftazidime arm than in the meropenem arm (median 5 versus 4 days, P = 0.022, and 7 versus 6 days, P = 0.009, respectively). With respect to the kind of infection, differences between the two arms were significant only in episodes classified as FUO but not in documented infections. In both arms, side effects were minimal. Despite the greater response rate for meropenem in FUO, the fact that ceftazidime has been proven to be as effective as meropenem in documented infections in the present study suggests that both drugs are useful as empirical monotherapy in febrile paediatric cancer patients.

Bacterial Infections↗
PubMed2001

Combined systemic and intraventricular chemotherapy in primary CNS lymphoma: a pilot study.

The objective was to evaluate response rate, response duration, and toxicity after systemic and intraventricular chemotherapy in primary CNS lymphoma (PCNSL). From September 1995 to September 1998, 20 consecutive patients with PCNSL (median age 64, range 27 to 71 years) were enrolled in a pilot study evaluating chemotherapy without radiotherapy. A high dose methotrexate (MTX) (cycles 1, 2, 4, 5) and cytarabine (ara-C) (cycles 3, 6) based systemic therapy (including dexamethasone, vinca alkaloids, ifosfamide, and cyclophosphamide) was combined with intraventricular MTX, prednisolone, and ara-C. Complete response was achieved in 11 and partial remission in two patients; in one response could not be determined. Four patients showed progressive disease and two (70, 71 years) died from treatment related complications. Observation time was 2 to 59 months (median 31.5 months). Kaplan-Meier estimate for median time to treatment failure (TTF) was 20.5 months, and for median survival 54 months. Systemic toxicity was mainly hematological. Ommaya reservoir infection occurred in four patients and acute transient MTX induced encephalopathy in two (subacute in another). Cognitive dysfunction possibly due to treatment was seen in only one patient after relapse and after a total of 12 cycles (six at relapse). In conclusion, primary chemotherapy based on high dose MTX and ara-C is highly efficient in PCNSL. Toxicity is manageable in patients younger than 70 years.

Adult↗
PubMed2001

Naive and memory T cells migrate in comparable numbers through the normal rat lung: only effector T cells accumulate and proliferate in the lamina propria of the bronchi.

T cells reach the lung via the pulmonary and bronchial arteries that supply the alveolar and bronchial regions. Although these regions are differentially affected by T cell-mediated diseases, the migration of T-cell subsets in these two regions has not been studied. Naive, memory, and effector T cells were injected into congenic rats and traced in sections of normal lung. All three T-cell subsets were found in large numbers in the alveolar region and exited again quickly. Only effector T cells accumulated in the lamina propria of the bronchi. Further, 72 h after injection 6% of the effector T cells still proliferated in the lung, whereas apoptotic effector T cells were only observed 1 h after injection (0.2%). Thus, not only effector and memory but also naive T cells continuously migrated through the lung. The preferential accumulation of effector T cells in the bronchial lamina propria may explain why some diseases preferentially affect the bronchial region.

Animals↗