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Biomedical subjects

D Binder

Publications and source records attributed to D Binder.

At least 19 recordsLinked to original sources
PubMed2006

Docetaxel/gemcitabine or cisplatin/gemcitabine followed by docetaxel in the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC): results of a multicentre randomized phase II trial.

BACKGROUND: Most patients (pts) with metastatic non-small cell lung cancer (NSCLC) receive either single agents or chemotherapy doublets. Recent studies have demonstrated that triple-agent therapies may improve the response rate, but are associated with significant toxicity, and frequently do not prolong survival. A sequential triple-agent schedule may combine acceptable tolerability and good efficacy. We therefore conducted a multicentre, prospectively randomized study that evaluates a sequential three-drug schedule and a platinum-free doublet regimen. PATIENTS AND METHODS: The pts with union international contre le cancer (UICC) stage IV NSCLC were randomized to one of two schedules: in arm Doc-Gem, they received gemcitabine (900 mg/m(2), 30 min infusion) on days 1 and 8, and docetaxel (75 mg/m(2), 1 h infusion) on day 1, repeated every 3 weeks up to six cycles. In arm Cis-Gem-->Doc, gemcitabine (900 mg/m(2), days 1 and 8) and cisplatin (70 mg/m(2), 1 h infusion, day 1) were given for three cycles, followed by three cycles of docetaxel (100 mg/m(2), day 1, repeated every 3 weeks). RESULTS: One hundred and thirteen pts were randomized to arms Doc-Gem (55 pts) and Cis-Gem-->Doc (58 pts). With Doc-Gem, 20.4% of pts responded to the treatment whereas 31.0% responded in arm Cis-Gem-->Doc (overall response, intent-to-treat, difference not significant). The median time to progression was 3.6 months in arm Doc-Gem [95% confidence interval (CI) 1.4, 5.9] and 5.2 months in arm Cis-Gem-->Doc (95% CI 3.1, 7.3). The median survival was 8.7 months with treatment Doc-Gem (95% CI 5.7, 11.6) and 9.4 months with treatment Cis-Gem-->Doc (95% CI 7.8, 11.0). The 1-year survival rates were 34 and 35%, respectively. Mild to moderate leukopenia was frequently seen with both schedules. Other common adverse events (AE) were nausea/vomiting, thrombocytopenia, anaemia, diarrhoea, and infections. No significant differences in AEs were observed between the schedules except for nausea/vomiting, which occurred more frequently with Cis-Gem-->Doc. CONCLUSION: The sequential therapy comprising cisplatin, gemcitabine, and docetaxel demonstrated promising tumour control whereas the platinum-free combination (docetaxel/gemcitabine) was very well tolerated. However, the schedules resulted in comparable survival to recent large trials in pts with advanced NSCLC. The present results do not justify further phase III investigation.

Adult↗
PubMed2006

[Brain metastases of lung cancer].

Cerebral metastases are a frequent complication of lung cancer. They often determine patients' prognosis and need urgent therapeutic intervention. Based on histologic type, former therapies, age and performance of the patient, the number of cerebral lesions and the extracerebral tumour activity, individualized treatments are applied. For patients who suffer from non-small cell lung cancer and a single CNS lesion the best results can be achieved if they are surgically resected or receive radiosurgery. Their survival time can be markedly increased in comparison to patients who undergo whole brain irradiation. If multiple metastases are seen in CT or MRI, whole brain irradiation is the therapy to choose. Furthermore it should be initiated if small cell lung cancer metastasizes to the brain. More aggressive local treatment options appear promising, but a clear role for them has not yet been defined. Systemic chemotherapy gains more attention in the treatment of small and non-small cell lung cancer with brain metastases. How to increase the efficacy through simultaneous application of chemo- and radiotherapy is tested in current trials. This article gives an overview on clinical presentation and diagnosis of cerebral metastases in lung cancer and reviews current treatment options.

Anticonvulsants↗
PubMed2004

[Myeloproliferative disorders].

Myeloproliferative disorders are caused by abnormalities of hematopoietic stem cells leading to uncontrolled proliferation of one or more cell lines in the blood. Besides sharing common clinical and hematologic features they are characterized by clonal hematopoiesis and genetic instability, resulting in a disease-specific rate of transformation into acute leukemia. This review discusses relevant clinical and prognostic aspects as well as current diagnostic and therapeutic procedures of polycythemia vera, essential thrombocythemia and chronic idiopathic myelofibrosis.

Bone Marrow↗
PubMed2003

Endovascular embolectomy of acute basilar artery occlusion.

Acute basilar artery occlusion has a mortality rate approaching 90%. The authors describe a case of acute basilar artery occlusion managed successfully with endovascular embolectomy. A 31-year-old man sought treatment for confusion, dysarthria, and right-sided weakness. He soon became unresponsive and was found to have a vertebral artery dissection and an associated basilar artery embolism. The dissection was managed with endovascular stenting, and the basilar artery embolus was removed with a clot retriever at 7 hours. The patient recovered without neurologic deficit.

Acute Disease↗
PubMed2000

[Neonatal alloimmune thrombocytopenia due to a rare anti-HPA-1b antibody].

Foetal and neonatal alloimmune thrombocytopenia is caused by transplacental transfer of antibodies directed against platelet antigens and affects approximately 1 in 1000-2500 neonates. Clinically relevant complications are the intracranial haemorrhages that occur in 10-20% of cases. 20 platelet antigen systems are currently known. However, immunisation is most frequently seen against two of these (HPA-1a and HPA-5b). Treatment options include transfusion of compatible or, if these are not available while urgently needed, random donor platelets, intravenous immunoglobulin, and steroids. We report on a case of neonatal alloimmune thrombocytopenia due to an anti-HPA-1b antibody in the third pregnancy of a 31-year-old Caucasoid woman. The infant was treated with repeated maternal and random donor platelet transfusions and with a single dose of intravenous immunoglobulin.

Adult↗
PubMed2000

Neuropathy under chemotherapy.

Neuropathy is a dose-limiting side effect for a number of effective chemotherapeutic agents. A better understanding of effective mechanisms will lead to novel treatment strategies that will protect neurons without decreasing therapeutic efficacy. The assessment of the efficacy and neurotoxicity of various chemotherapeutic agents is vital, for a determination of the maximum allowable dose. The introduction of chemotherapy in the 50s and 60s of the twentieth century has resulted in the development of curative therapeutic interventions for patients with several types of solid tumours and hemopoietic neoplasms. The important obstacles encountered in the use of chemotherapy have been the toxicity to the normal tissue. During the past 8 years there has come about a new level of understanding of the mechanisms through which chemotherapeutic agents work. This has opened the door to new paradigms of treatment in which molecular, genetic, and biologic therapy can be used together to increase the sensitivity of abnormal cells to treatment, and to protect the normal tissues of the body from therapy-induced side effects. The implementation of new strategies could change the way therapy is delivered over the next few years and improve the outcome especially in patients with neoplasms that are currently resistant to conventional dose therapy.

Antineoplastic Agents↗
PubMed2000

Further evidence for oxidant-induced vascular endothelial growth factor up-regulation in the bronchoalveolar lavage fluid of lung cancer patients undergoing radio-chemotherapy.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent inducer of physiological and neoplastic blood vessel growth. Moreover, in vitro studies have demonstrated that VEGF can be up-regulated by conditions associated with the generation of free radicals and reactive oxygen species. In a previous study we reported on strongly increased VEGF concentrations in the bronchoalveolar lavage fluid (BALF) of patients with lung cancer under therapy. In this study we aimed to reveal whether this increase was due to the therapy-associated intrapulmonary oxidative burden. PATIENTS AND METHODS: A total of 103 BALF samples from 94 patients with lung cancer (82 patients with non-small-cell lung cancer, 12 patients with small-cell lung cancer) were studied at different times before, during or after cancer treatment. VEGF levels in the lavage fluid and ratios of oxidised methionine in proteins of epithelial lining fluid (ELF) were determined. RESULTS: As reported previously, strongly increased VEGF levels in the ELF were observed in patients undergoing chemotherapy when radiotherapy had been administered before. Increased levels of oxidised methionine indicated that these patients suffered from severe pulmonary oxidative stress that was significantly less in patients undergoing only chemotherapy. Similarly, VEGF concentrations in the ELF were significantly elevated in cancer patients at the time of diagnosis, but the oxidised methionine levels did not reveal significant oxidant/antioxidant imbalances in these patients. CONCLUSION: Systemic chemotherapy is associated with oxidative stress in vivo, which is more pronounced if patients are additionally treated with radiation. VEGF levels in the ELF are increased by this condition as well as by the activity of the tumour itself.

Adult↗
PubMed1999

Increased levels of vascular endothelial growth factor in bronchoalveolar lavage of patients with bronchial carcinoma effect of tumour activity and oxidative stress due to radio-chemotherapy?

BACKGROUND: Vascular endothelial growth factor (VEGF) plays a crucial role in physiological and neoplastic angiogenesis. Moreover, VEGF has been found to be upregulated by conditions associated with the generation of free radicals and reactive oxygen intermediates. In patients with cancer, studies to evaluate VEGF as a measure of tumour activity were carried out. We tested the hypothesis that VEGF is additionally affected by oxidative stress due to anticancer therapy. Moreover, the suitability of epidermal growth factor (EGF) to estimate tumour activity was studied. PATIENTS AND METHODS: 60 patients with non-small cell lung cancer (NSCLC) covering different therapy progress and modalities underwent bronchoalveolar lavage. VEGF-, EGF-, albumin- and total protein-concentrations in bronchoalveolar lavage fluid (BALF) and VEGF-levels in blood plasma were studied. RESULTS: BALF VEGF-levels were increased in patients with advanced NSCLC before and in anticancer therapy. In patients who had received radiotherapy to the lung prior to chemotherapy, VEGF concentrations were noticeably higher than under sole chemotherapy. Pulmonary endothelial hyperpermeability was found in patients with recently diagnosed tumours and patients undergoing anti-cancer therapy. Evaluation of EGF-levels in BALF revealed no significant influence of tumour activity or cancer therapy on this parameter. CONCLUSION: BALF-levels of VEGF are affected by tumour activity and oxidative stress due to anticancer therapy.

Adult↗
PubMed1999

Oxidant-induced lung injury in anticancer therapy.

Lung injury is one of the most frequent side effects in anticancer therapy. Especially simultaneous application of high doses of ionising radiation and radiosensitising cytotoxic drugs is considered to cause deleterious pneumonitis and pulmonary fibrosis. Growing evidence indicates that reactive oxygen species (ROS) play a key role in the development of these disorders. They are capable of causing cell component alterations and changing cellular protein expression. Observing these disease mechanisms reveals an impressive self-amplifying cascade of secondary ROS generation. Through intricate interactions between cells, cytokines and growth factors, fibroblasts are activated and thus pulmonary matrix content is massively increased. - As clinical appearance is uniform and unspecific, an early, reliable diagnosis of therapy-associated lung damage is not possible so far. However, improving this situation could enable us to take advantage of new multimodal therapeutic facilities. This review discusses mechanisms of ROS generation during radio-chemotherapy in the lung, antioxidant defense strategies and responses to oxidants, thereby assessing current diagnostic tools.

Animals↗
PubMed1998

Aplastic anemia rescued by exhaustion of cytokine-secreting CD8+ T cells in persistent infection with lymphocytic choriomeningitis virus.

Aplastic anemia may be associated with persistent viral infections that result from failure of the immune system to control virus. To evaluate the effects on hematopoiesis exerted by sustained viral replication in the presence of activated T cells, blood values and bone marrow (BM) function were analyzed in chronic infection with lymphocytic choriomeningitis virus (LCMV) in perforin-deficient (P0/0) mice. These mice exhibit a vigorous T cell response, but are unable to eliminate the virus. Within 14 d after infection, a progressive pancytopenia developed that eventually was lethal due to agranulocytosis and thrombocytopenia correlating with an increasing loss of morphologically differentiated, pluripotent, and committed progenitors in the BM. This hematopoietic disease caused by a noncytopathic chronic virus infection was prevented by depletion of CD8+, but not of CD4+, T cells and accelerated by increasing the frequency of LCMV-specific CD8+ T cells in T cell receptor (TCR) transgenic (tg) mice. LCMV and CD8+ T cells were found only transiently in the BM of infected wild-type mice. In contrast, increased numbers of CD8+ T cells and LCMV persisted at high levels in antigen-presenting cells of infected P0/0 and P0/0 x TCR tg mice. No cognate interaction between the TCR and hematopoietic progenitors presenting either LCMV-derived or self-antigens on the major histocompatibility complex was found, but damage to hematopoiesis was due to excessive secretion and action of tumor necrosis factor (TNF)/lymphotoxin (LT)-alpha and interferon (IFN)-gamma produced by CD8+ T cells. This was studied in double-knockout mice that were genetically deficient in perforin and TNF receptor type 1. Compared with P0/0 mice, these mice had identical T cell compartments and T cell responses to LCMV, yet they survived LCMV infection and became life-long virus carriers. The numbers of hematopoietic precursors in the BM were increased compared with P0/0 mice after LCMV infection, although transient blood disease was still noticed. This residual disease activity was found to depend on IFN-gamma-producing LCMV-specific T cells and the time point of hematopoietic recovery paralleled disappearance of these virus-specific, IFN-gamma-producing CD8+ T cells. Thus, in the absence of IFN-gamma and/or TNF/LT-alpha, exhaustion of virus-specific T cells was not hampered.

Anemia, Aplastic↗
PubMed1998

Uncomplicated baseline fetal tachycardia or bradycardia in postterm pregnancies and perinatal outcome.

OBJECTIVE: to assess perinatal outcome in post-term pregnancies in which fetal heart rate (FHR) monitoring revealed either uncomplicated baseline fetal tachycardia (> or = 160 bpm) or fetal bradycardia (< or = 120 bpm). STUDY DESIGN: We performed a case-control study of patients who underwent fetal assessment between July 1989 and June 1995, as part of post-term evaluation. Inclusion criteria consisted of nonlaboring afebrile patients with singleton post-term pregnancies > or = 41 weeks of gestation by strict dating criteria (last menstrual period consistent with ultrasound biometric parameters obtained prior to 20 weeks' gestation), normal fetal anatomy, intact membranes, and reactive nonstress test with no evidence of chorioamnionitis. Patients with fetal tachy or brady arrhythmias, FHR decelerations, or loss of short-term beat-to-beat variability were excluded. Baseline FHR was recorded retrospectively by an observer blinded to maternal and neonatal clinical outcome. For each case of uncomplicated baseline fetal tachycardia (> or = 160 bpm) or bradycardia (< or = 120 bpm), either two or three control cases (matched for maternal age and parity), with FHR > 120 bpm and < 160 bpm, were identified. Outcome variables assessed included: incidence of cesarean delivery, nuchal cord at delivery, meconium-stained amniotic fluid (AF), 5-min Apgar score < 7, fetal growth restriction (< 10th percentile for 41 weeks' gestation), meconium aspiration syndrome, and neonatal intensive care unit (NICU) admission. Statistical analysis included two-tailed t-test and chi2 test when appropriate, with p < 0.05 considered significant throughout. RESULTS: During the study period 1390 post-term patients (6.81% of the general population) were assessed. Of these, 31 (2.23%) fetuses exhibited baseline FHR > or = 160 bpm, and 76 fetuses (5.46%) exhibited baseline FHR < or = 120 bpm. No significant differences were noted in the incidence of cesarean delivery, presence of nuchal cord at delivery, meconium-stained AF, 5-min Apgar scores < 7, fetal growth restriction, meconium aspiration syndrome, or the incidence of NICU admissions between the groups of patients with fetal tachycardia, bradycardia, and their respective controls. CONCLUSIONS: Uncomplicated baseline fetal tachycardia or bradycardia in postterm patients are not associated with an increase in the incidence of adverse perinatal outcome.

Bradycardia↗
PubMed1997

Virus-induced transient bone marrow aplasia: major role of interferon-alpha/beta during acute infection with the noncytopathic lymphocytic choriomeningitis virus.

The hematologic consequences of infection with the noncytopathic lymphocytic choriomeningitis virus (LCMV) were studied in wild-type mice with inherent variations in their interferon (IFN)-alpha/beta responder ability and in mutant mice lacking alpha/beta (IFN-alpha/beta R0/0) or gamma IFN (IFN-gamma R0/0) receptors. During the first week of infection, wild type mice demonstrated a transient pancytopenia. Within a given genetic background, the extent of the blood cell abnormalities did not correlate with the virulence of the LCMV isolate but variations were detected between different mouse strains: they were found to depend on their IFN-alpha/beta responder phenotype. Whereas IFN-gamma R0/0 mice were comparable to wild-type mice, IFN-alpha/beta R0/0 mice exhibited unchanged peripheral blood values during acute LCMV infection. In parallel, the bone marrow (BM) cellularity, the pluripotential and committed progenitor compartments were up to 30-fold reduced in wild type and IFN-gamma R0/0, but remained unchanged in IFN-alpha/beta R0/0 mice. Viral titers in BM 3 d after LCMV infection were similar in these mice, but antigen localization was different. Viral antigen was predominantly confined to stromal BM in normal mice and IFN-gamma R0/0 knockouts, whereas, in IFN-alpha/beta R0/0 mice, LCMV was detected in > 90% of megakaryocytes and 10-15% of myeloid precursors, but not in erythroblasts Although IFN-alpha/beta efficiently prevented viral replication in potentially susceptible hematopoietic cells, even in overwhelming LCMV infection, unlimited virus multiplication in platelet and myeloid precursors in IFN-alpha/beta R0/0 mice did not interfere with the number of circulating blood cells. Natural killer (NK) cell expansion and activity in the BM was comparable on day 3 after infection in mutant and control mice. Adaptive immune responses did not play a major role because comparable kinetics of LCMV-induced pancytopenia and transient depletion of the pluripotential and committed progenitor compartments were observed in CD8(0/0) and CD4(0/0) mice, in mice depleted of NK cells, in lpr mice, and in perforin-deficient (P0/0) mice lacking lytic NK cells. Thus, the reversible depression of hematopoiesis during early LCMV infection was not mediated by LCMV-WE-specific cytotoxic T lymphocyte, cytolysis, or secreted IFN-gamma from virally induced NK cells but was a direct effect of IFN-alpha/beta.

Acute Disease↗
PubMed1996

Temporal events in cyclopean vision.

The majority of neurons in the primary visual cortex of primates can be activated by stimulation of either eye; moreover, the monocular receptive fields of such neurons are located in about the same region of visual space. These well-known facts imply that binocular convergence in visual cortex can explain our cyclopean view of the world. To test the adequacy of this assumption, we examined how human subjects integrate binocular events in time. Light flashes presented synchronously to both eyes were compared to flashes presented alternately (asynchronously) to one eye and then the other. Subjects perceived very-low-frequency (2 Hz) asynchronous trains as equivalent to synchronous trains flashed at twice the frequency (the prediction based on binocular convergence). However, at higher frequencies of presentation (4-32 Hz), subjects perceived asynchronous and synchronous trains to be increasingly similar. Indeed, at the flicker-fusion frequency (approximately 50 Hz), the apparent difference between the two conditions was only 2%. We suggest that the explanation of these anomalous findings is that we parse visual input into sequential episodes.

Animals↗
PubMed1995

[Acute liver failure following tetrabamate].

Tetrabamate (Atrium), a composite preparation of phenobarbital, difebarbamate and febarbamate, is widely used to reduce ethanol withdrawal symptoms such as tremor, agitation and anxiety. Generally this drug is well tolerated and a few cases of reversible hepatitis as well as clinically mild symptoms of asthenia have been described. We report on a 28-year-old female patient admitted to hospital with acute liver failure after treatment with tetrabamate because of alcohol withdrawal symptoms. Liver biopsy revealed a drug-induced toxic alteration with extensive panlobular necrosis without signs of alcoholic hepatitis. Under supportive therapy liver parameters normalized in 3 months. In view of this potentially lethal adverse effect of tetrabamate, it should not be used for ethanol withdrawal symptoms.

Adult↗