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M Burk

Publications and source records attributed to M Burk.

At least 19 recordsLinked to original sources
PubMed2004

Randomized phase III study of gemcitabine and vinorelbine versus gemcitabine, vinorelbine, and cisplatin in the treatment of advanced non-small-cell lung cancer: from the German and Swiss Lung Cancer Study Group.

PURPOSE: To evaluate whether cisplatin-based chemotherapy (gemcitabine, vinorelbine, and cisplatin [GVP]) prolongs overall survival in comparison to cisplatin-free chemotherapy (gemcitabine and vinorelbine [GV]) as first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between September 1999 and June 2001, 300 patients with NSCLC stage IIIB with malignant pleural effusion or stage IV disease were randomly assigned to receive GV (gemcitabine 1000 mg/m(2) + vinorelbine 25 mg/m(2) on days 1 and 8 every 3 weeks) or GVP (gemcitabine 1000 mg/m(2) + vinorelbine 25 mg/m(2) on days 1 and 8 + cisplatin 75 mg/m(2) on day 2 every 3 weeks). Primary end point of the study was overall survival. RESULTS: Two hundred eighty-seven patients (GV, 143 patients; GVP, 144 patients) were eligible for analysis. At the time of analysis, April 15, 2002, 209 patients (GV, 103 patients; GVP, 106 patients) of 287 patients had died (73%). No statistically significant difference was observed for overall survival (P =.73; median survival, 35.9 versus 32.4 weeks; 1-year survival rate, 33.6% versus 27.5%) as well as for event-free survival (P =.35; median time-to-event, 19.3 versus 22.3 weeks) between GV and GVP. Two hundred fourteen patients were assessable for best response. The overall response rates were 13.0% for GV versus 28.3% for GVP (P =.004; complete responders, 0% versus 3.8%; partial responders, 13.0% versus 24.5%). Hematologic and nonhematologic toxicity was significantly lower in the GV treatment arm compared with GVP. No statistically significant difference in quality of life was observed. CONCLUSION: In this phase III study, the cisplatin-based GVP regimen showed no survival benefit as first-line chemotherapy in advanced NSCLC when compared with the cisplatin-free GV regimen, which was substantially better tolerated.

Adolescent↗
PubMed1998

Lateralized human cortical activity for shifting visuospatial attention and initiating saccades.

Lateralized human cortical activity for shifting visuospatial attention and initiating saccades. J. Neurophysiol. 80: 2900-2910, 1998. The relation between shifts of visual attention and saccade preparation was investigated by studying their electrophysiological correlates in human scalp-recorded electroencephalogram (EEG). Participants had to make saccades either to a saliently colored or to a gray circle, simultaneously presented in opposite visual hemifields, under different task instructions. EEG was measured within the short interval between stimulus onset and saccade, focusing on lateralized activity, contralateral either to the side of the relevant stimulus or to the direction of the saccade. Three components of lateralization were found: 1) activity contralateral to the relevant stimulus irrespective of saccade direction, peaking 250 ms after stimulus onset, largest above lateral parietal sites, 2) activity contralateral to the relevant stimulus if the stimulus was also the target of the saccade, largest 330-480 ms after stimulus onset, widespread over the scalp but with a focus again above lateral parietal sites, and 3) activity contralateral to saccade direction, beginning about 100 ms before the saccade, largest above mesial parietal sites, with some task-dependent fronto-central contribution. Because of their sensitivity to task variables, component 1 is interpreted as the shifting of attention to the relevant stimulus, component 2 is interpreted as reflecting the enhancement of the attentional shift if the relevant stimulus is also the saccade target, and component 3 is interpreted as the triggering signal for saccade execution. Thus human neurophysiological data provided evidence both for independent and interdependent processes of saccade preparation and shifts of visual attention.

Adult↗
PubMed1998

Dyshematopoiesis in de novo acute myeloid leukemia: cell biological features and prognostic significance.

Dyshematopoiesis was found in 44 (42.3%) of 104 cases of de novo acute myeloid leukemia (AML). Dyshematopoietic AML (dys-AML) and AML without hematopoietic dysplasia (non-dys-AML) were compared with regard to biological, hematological, immunophenotypic, and cytogenetic parameters as well as prognostic criteria. Median age of patients was 55 years in both groups. In dys-AML, the median leukocyte count (p = 0.04), peripheral blast (p = 0.02) and medullary blast cell count (p < 0.001) were significantly decreased, whereas the median platelet count (p - 0.04) was increased. Immunophenotyping demonstrated that leukemic blast cells in dys-AML more frequently expressed the adhesion molcules CD54 (p = 0.05) and CD58 (p = 0.08) than leukemic cells in non-dys-AML. Cytogenetically, we distinguished two karyotypic patterns, one group with a normal karyotype or prognostically favorable single chromosome aberrations ("P(0)-karyotype"), and another one with unfavorable single aberrations or complex aberrations ("P(1)-karyotype"). The incidence of these groups was not significantly different between dys-AML and non-dys-AML. Complete remission rate (CRR) after induction chemotherapy (p = 0.03) and overall survival time (OS; p = 0.03) were significantly lower in dys-AML. In addition, median disease free survival (DFS; p = n.s.) was inferior compared to non-dys-AML. In the dys-AML as well as in the non-dys-AML patient group, CRR, DFS, and OS were decreased in the P(1)-compared to the P(0)-subgroup. We conclude that dyshematopoietic AML is characterized by specific cell biological features and that hematopoietic and cytogenetic status represent complementary prognostic factors in de novo AML.

Acute Disease↗
PubMed1997

A randomized trial of a nonabsorbable antibiotic lozenge given to alleviate radiation-induced mucositis.

BACKGROUND: The objective of this study was to determine whether a nonabsorbable antibiotic lozenge could alleviate radiation-induced oral mucositis. METHODS: Patients scheduled to receive radiation therapy to more than one-third of the oral cavity mucosa were selected for the study. After stratification, patients were randomized to receive either a nonabsorbable antibiotic lozenge or a placebo. Both groups were then evaluated for mucositis by health care providers and self-report instruments. RESULTS: Fifty-four patients were randomized to receive the antibiotic lozenge and 58 to receive the placebo. There were no substantial differences or trends in mucositis scores between the two study arms as measured by the health care providers. However, the mean patient-reported mucositis score and the duration of patient-reported Grade 3-4 mucositis were both lower in the patients randomized to the antibiotic lozenge arm (P = 0.02 and 0.007, respectively). CONCLUSIONS: This prospective, controlled trial provides evidence to suggest that a nonabsorbable antibiotic lozenge can decrease patient-reported radiation-induced oral mucositis to a modest degree. Nonetheless, this evidence does not appear to be compelling enough to recommend this treatment as part of standard practice.

Aged↗
PubMed1997

Acquired factor VIII inhibitors in nonhemophilic patients.

Antibodies against factor VIII occur in about 15-35% of hemophilia A patients and induce refractoriness to factor VIII substitution. In most cases, these antibodies are of the IgG class. Strategies to avoid or to treat such inhibitors are controversial. In very rare cases, factor VIII inhibitors also develop in nonhemophilic patients. Although there are anecdotal reports that these antibodies may disappear spontaneously without occurrence of bleeding tendencies, in the majority of patients the clinical course is characterized by severe hemorrhages. From 1980 to 1995, we observed ten nonhemophilic patients with acquired factor VIII inhibitors at our hospital. In most cases, a sudden bleeding tendency was observed shortly after an injury or surgery. Coagulation tests showed a prolonged aPTT and a decreased F VIII level. Other deficiencies of blood-clotting factors and acquired or hereditary von Willebrand's disease were excluded. Therapy with F VIII concentrates did not produce the expected increase. Measurement of F VIII inhibitor levels in Bethesda units/ml (BU/ml) revealed maximal values in the range of 2-128 BU/ml. Immunosuppressive therapy with azathioprine or cyclophosphamide in combination with methylprednisolone led to complete disappearance of the inhibitor, normalization of the coagulation tests, and complete remission of the bleeding tendency in seven treated patients within 6 weeks. Although the clinical course is not predictable and inhibitors may disappear spontaneously, combined therapy with methylprednisolone and azathioprine or cyclophosphamide is recommended for patients with bleeding tendency. In pregnancy, therapy should be started only with methylprednisolone; post-partum, azathioprine should be used additionally if methylprednisolone as a single drug does not lead to complete remission. In emergency situations, therapy with high doses of human factor VIII concentrate may be used. When bleeding does not cease, the additional use of activated prothrombin-complex concentrates or porcine factor VIII is indicated. Possible side effects may include hepatitis and short-lived intravascular thrombin production.

Adult↗
PubMed1997

Pseudomonas aeruginosa blepharoconjunctivitis during cytoreductive chemotherapy in a woman with acute lymphocytic leukemia.

Patients undergoing chemotherapy regimens for hematologic malignancies are prone to develop unusual and potentially life-threatening infections during periods of leukopenia- induced immunosuppression. We report the case of a woman who received consolidation chemotherapy for acute lymphocytic leukemia and acquired necrotizing Pseudomonas aeruginosa blepharoconjunctivitis of the right eye during a period of mild leukopenia. The infection led to severe orbital and periorbital inflammation, spreading down to the neck. High-dose antibiotic treatment with ceftazidime and tobramycin combined with granulocyte cell-stimulating factor cleared the infection after several days, but plastic surgery was needed to restore normal eye closure.

Adult↗
PubMed1997

Pharmacokinetics of high-dose cytarabine and its deamination product--a reappraisal.

Cytarabine is intracellularly activated and correlations have been established between the pharmacokinetic behaviour of active metabolites and their antileukemic effect. Recently, a good response to high-dose treatment of leukemias has additionally been attributed to a so-called low deamination phenotype of cytarabine inactivation. Consequently, these findings would support plasma level monitoring of cytarabine and its metabolite uracil arabinoside in high-dose cytarabine regimens. This pharmacokinetic study presents data attempting to reevaluate these observations. Thirty-seven patients were treated by 3-h high-dose cytarabine infusions (9 patients 1000 mg/m2, 28 patients 3000 mg/m2) as part of their treatment for acute leukemia. Serial blood samples during and post infusion were analysed for cytarabine (araC) and its deamination product uracil arabinoside (araU) using HPLC with UV-detection. Considerable interindividual variation was observed in end-infusion plasma concentrations of araC (1000 mg/m2: 2.1-fold, 3000 mg/m2: 5.5-fold) and araU (1000 mg/m2: 2.7-fold, 3000 mg/m2: 2.9-fold). The median ratio of end infusion concentrations araU/araC (on a molar basis) was 5.6 (S.D. 3.0), extreme ratio values were 2 and 14. No differences of the araU/araC ratio were found between the two dosages used. Minimum plasma araC concentrations at the end of infusion were 10.5 micromol/l and 22.0 micromol/l at a dose of 1000 and 3000 mg/m2, respectively. In our European study population a "fast" deamination phenotype of cytarabine (araU/araC ratio > 14) was not be observed.

Acute Disease↗
PubMed1996

Phase III double-blind evaluation of an aloe vera gel as a prophylactic agent for radiation-induced skin toxicity.

PURPOSE: Considerable pilot data and clinical experience suggested that an aloe vera gel might help to prevent radiation therapy-induced dermatitis. METHODS AND MATERIALS: Two Phase III randomized trials were conducted. The first one was double blinded, utilized a placebo gel, and involved 194 women receiving breast or chest wall irradiation. The second trial randomized 108 such patients to aloe vera gel vs. no treatment. Skin dermatitis was scored weekly during both trials both by patients and by health care providers. RESULTS: Skin dermatitis scores were virtually identical on both treatment arms during both of the trials. The only toxicity from the gel was rare contact dermatitis. CONCLUSIONS: This dose and schedule of an aloe vera gel does not protect against radiation therapy-induced dermatitis.

Adult↗
PubMed1996

Pathologic rupture of the spleen in hematologic malignancies: two additional cases.

Pathologic rupture of the spleen in hematologic malignancies is rare. We present two cases of splenic rupture which occurred in a man with a secondary high-grade non-Hodgkin's lymphoma and a woman with chronic lymphocytic leukemia (CLL). In a review of the literature, we have been able to identify 136 cases of pathologic splenic rupture since 1861; 34% have occurred in acute leukemias, 34% in non-Hodgkin's lymphomas, and 18% in chronic myelogenous leukemia (CML). We find a male-to-female ratio of 3:1, with considerable differences for the specific diseases encountered. Pathologic rupture of the spleen has happened almost exclusively in adults and the ruptured spleens are generally moderately to severely enlarged. It seems that, apart from splenic infiltration by a hematologic disease, splenic infarcts and coagulation disorders (which have previously been advanced as the most important pathophysiologic factors leading to rupture), male sex, adulthood, severe splenomegaly, and cytoreductive chemotherapy may increase the risk for pathologic splenic rupture. We briefly discuss symptoms preceding the event, diagnostic possibilities, and the outcome with operative and conservative approaches.

Fatal Outcome↗
PubMed1995

Erythrocyte indices as screening tests for the differentiation of microcytic anemias.

Algorithms for the differential diagnosis of anemias are commonly based on suspected incidences and simple laboratory parameters. Especially microcytic anemias are diagnosed using algorithms created in Mediterranean or Northern American regions. In a West German region we observe relatively high diagnostic uncertainty regarding common forms of anemias. As a hypothesis, this may be a result of inadequate algorithms not designed for regions with high incidences of anemias of chronic disease and low incidences of thalassemias. To further elucidate diagnostic problems we here report the frequencies of anemias in university hospital outpatients. Based on these data, the diagnostic values of different erythrocyte indices and of red cell distribution width in the differential diagnosis of anemias were calculated. 4525 patient files were reviewed retrospectively. 872 patients presented with anemia, 107 of which were hereditary forms and 765 of other forms. In hereditary anemias the frequency of thalassaemias (50 patients) and corpuscular hemolytic anemias (49 patients) was the same. Nearly half of the other anemias were covered by anemias of chronic disease and true iron deficiency anemias. Several indices intended to separate thalassemias from other microcytic anemias were tested for relevance. Sensitivity was between 0.75 and 0.85. Specificity was between 0.78 and 0.95. Red cell distribution width was not significantly different between thalassemias and iron deficiency. Only a red cell distribution width above 17.0 resulted in a specificity for iron deficiency of 0.91. Red cell distribution width is considered to be an unreliable screening test in a population with a low incidence of thalassemias. The high incidence of anemias of chronic disease in the region investigated should lead to more complex diagnostic procedures than offered by blood count values alone.

Anemia↗
PubMed1995

Cutaneous bacillary angiomatosis in a patient with chronic lymphocytic leukemia.

BACKGROUND: Bacillary angiomatosis is a recently described vascular disorder that is associated with infection by Bartonella henselae (formerly known as Rochalimaea henselae) and Bartonella quintana (formerly known as Rochalimaea quintana); this disorder usually occurs in patients with human immunodeficiency virus infection. We report a case of cutaneous bacillary angiomatosis that occurred in a patient with chronic lymphocytic leukemia. OBSERVATIONS: A 55-year-old man with chronic lymphocytic B-cell leukemia, Rai stage IV, presented with multiple angiomatous papules that clinically resembled pyogenic granulomas. Histopathologic examination revealed circumscribed lobules of small vessels with plump endothelial cells, numerous neutrophils, and abundant nuclear dust; these features were diagnostic for bacillary angiomatosis. The diagnosis was confirmed by the Grocott-Gomori methenamine-silver nitrate stain that revealed argyrophilic bacteria and by ultrastructural demonstration of bacillary structures with trilaminar walls. Treatment with clarithromycin led to complete resolution of the lesions within 4 weeks. CONCLUSIONS: This case emphasizes that (1) bacillary angiomatosis must be considered in the differential diagnosis of vascular lesions in immunocompromised patients without human immunodeficiency virus infection, (2) Grocott-Gomori methenamine-silver nitrate stain is a simple and satisfactory alternative to the Warthin-Starry stain for the demonstration of bacilli in this condition, and (3) clarithromycin is an effective oral antibiotic for the treatment of this disease.

Angiomatosis, Bacillary↗
PubMed1995

Ion-pair liquid chromatography of cytarabine and uracil-arabinoside in human plasma.

An ion-pair high pressure liquid chromatographic method is described for the determination of cytarabine (CAS 147-94-4, araC) in human plasma. Complete separation is achieved within 10 min using a reversed stationary phase and an isocratic eluent containing 0.4 mmol/l heptane sulfonic acid as modifier. Detection by UV-absorption occurs at 270 nm. Quantification of cytarabine and of its main plasma metabolite uracil arabinoside (araU) is achieved by means of internal standardisation using adenine arabinoside (araA). Retention times of araU, araC, and araA are 3.9, 5.9 and 9.4 min, respectively. Detection limits of araC and araU are 10 and 15 ng/ml, resp. During a pharmacokinetic study of high-dose cytarabine treatment no interferences could be observed in plasma samples.

Adult↗
PubMed1995

In vitro formation of "urinary stones": generation of spherulites of calcium phosphate in gel and overgrowth with calcium oxalate using a new flow model of crystallization.

Calcium phosphate (CaP) has been detected in the majority of urinary stones containing predominantly calcium oxalate (CaOx). Therefore, crystal phases of CaP might play an important role with respect to the formation of urinary calcium stones in general. Very often, CaP found in stones or tissue of human kidney occurs in the shape of small spherulites. In this paper, we report on a new flow model of crystallization (FMCG), which has been used to generate spherulites of CaP in a gel matrix of 1% agar-agar at 37 degrees C from a supersaturated, metastable solution continuously flowing over the gel surface. Scanning electron microscopy (SEM), X-ray diffraction and microscopic Fourier transformed infrared spectroscopy (FTIR) revealed that the particles formed (diameter: up to 200 microns) consisted of a poorly crystalline core of carbonatoapatite which was partly surrounded by a well-crystallized shell of octacalcium phosphate (OCP) showing radially oriented sheet-like structures. Subsequently, CaOx was grown on these spherulites from a flow of a correspondingly supersaturated solution conducted over the gel matrix. It could be shown by SEM that growth of calcium oxalate monohydrate (COM) was characteristically induced by the OCP shell. Radial sheet-like forms of OCP were directly continued by COM showing a certain radial orientation. The model of crystallization in gel matrices applied here should be well-suited to simulate the process of urinary stone formation under in vitro conditions.

Calcium Oxalate↗
PubMed1994

Results of conventional-dose cytosine arabinoside and idarubicin in elderly patients with acute myeloid leukemia.

Conventional-dose Ara-C (200 mg/m2 d 1-5) combined with idarubicin (12 mg/m2 d 1-3) was employed as remission induction and consolidation therapy in 23 elderly AML patients with a median age of 66 years (range, 60-75) with AML according to the FAB criteria (M1 n = 3, M2 n = 10, M4 n = 6, M5 n = 2, M6 n = 2), eligible for the study. In seven patients earlier MDS had been documented by previous bone marrow aspirates. The CR rate after one induction course was 65% (15/23). Toxicity was acceptable, with four patients dying during the chemotherapy-induced hypoplasia (4/23). Although 80% of the CR patients received two additional cycles of Ara-C and idarubicin as consolidation therapy, only two patients are still in continuous complete remission more than 12 months after achieving CR. The median disease-free survival of the CR patients was 11.5 months and the median survival of the entire group was 10 months. We conclude that conventional dose Ara-C/idarubicin is an effective protocol for inducing complete remission in elderly patients with AML, but that consolidation therapy consisting of two courses of the same regimen does not produce a relevant rate of long-term disease-free survival.

Acute Disease↗
PubMed1994

Deficiency of both protein C and protein S in a family with ischemic strokes in young adults.

Protein C and protein S deficiencies increase the risk of venous thrombosis and pulmonary embolism, but their role in arterial thrombosis or embolism is controversial. We describe cerebral ischemia in two young women in a family with inherited deficiencies of both proteins C and S and provide evidence that a combined deficiency of proteins C and S may be a high risk factor for ischemic stroke in young adults.

Adult↗