Recurrent thromboembolism in two unrelated patients with double heterozygosity for factor V R506Q and factor II 20210G/A mutations.
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Adult↗
Biomedical subjects
M Wolf
Publications and source records attributed to M Wolf.
[Knowledge of physicians and dentists about biomathematical-epidemiologic methods].
A multiple-choice test questionnaire on statistical terms and methods was sent to 600 randomly selected physicians and dental surgeons and was returned by 264 (27%) of them: 183 physicians and 81 dental surgeons. The median number of correct answers for physicians was 10.1, markedly higher than the 6.2 scored by dental surgeons. At least half of the questions were correctly answered by 60% of the physicians and nearly 14% of the dental surgeons. Whereas some 14% of physicians had a good knowledge of statistical methods (with more than 2/3 of questions answered correctly), this was true of only 2.5% of the questioned dental surgeons. The results suggest that the majority of physicians and dental surgeons, especially the latter, are not capable of profiting from statistically orientated scientific articles. Moreover, the low percentage of questionnaires returned by dental surgeons may well indicate that, as a group, their statistical skills are far lower than even the results of this questionnaire would indicate. A need is seen for the education of dental surgeons to be bound more closely to that for human medicine.
Computational Biology↗
In vitro skewing of TCR transgenic CD4+ T cells from interleukin-2 deficient mice towards Th1 and Th2 in the absence of exogenous interleukin-2.
Previous experiments from several groups have indicated that in vitro priming for Th2 cells rigorously requires IL-4 but also depends on IL-2 [1-3]. On the other hand, IL-2 deficient mice characteristically have highly increased serum levels of the Th2-dependent isotypes IgG1 and IgE [4]. The overproduction of these isotypes is lost in IL-2 x IL-4 double deficient animals [5]. To readdress the question of a need for IL-2 for Th2 skewing in vitro we used T cells from IL-2-/- mice also transgenic for the DO11.10 TCR which is specific for OVA + IAd [6]. CD4+ cells from these mice were primed in vitro on IL-2-/- dendritic cells in the presence of OVA peptide and IL-4, IL-12 and IL-15, respectively. Following restimulation, cytokine production was analysed by intracellular staining with anti IL-4 and anti IFNgamma antibodies and flow cytometry. The data show that IL-4 primes IL-2-/- T cells for IL-4 production even in the absence of exogenous IL-2, while IL-12, as expected, polarises towards IFNgamma production. The ability to be primed for IL-4 production in the absence of IL-2 was also exhibited by naive CD4+CD62LlowTCR transgenic IL-2-/- cells and thus was not restricted to the CD44high CD62Llow cells which make up a high proportion of CD4+ cells in IL-2 deficient mice. We conclude that IL-2 is not absolutely required for in vitro skewing of naive T cells towards Th2.
Animals↗
[Informed consent: what is the question? Correlation between practice and theory].
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Humans↗
[Prognostic factors and therapeutic strategy in non-small-cell bronchial carcinoma].
The choice of treatment in non-small cell lung cancer depends on the extent of the disease. Stage of disease is not sufficiently accurate to predict outcome in NSCLC. The influence of patient and treatment characteristics on survival are reviewed. Surgery remains the cornerstone of treatment for stages I and II, and in some cases for stage IIIa. Investigational new prognostic factors such as K-ras mutations, Her2/Neu, BCL-2 protein, p53-expression/mutation may possibly define patient populations with poorer prognosis, who might benefit from a more intensive treatment. The treatment strategy of the university hospital of Marburg is presented.
Carcinoma, Non-Small-Cell Lung↗
Neutrophil-activating peptide-2 and melanoma growth-stimulatory activity are functional as monomers for neutrophil activation.
Neutrophil-activating peptide-2 (NAP-2) and melanoma growth-stimulatory activity (MGSA) are members of the chemokine family of inflammatory proteins. The structures of NAP-2, determined by x-ray crystallography, and MGSA, elucidated by NMR spectroscopy, revealed a tetramer and dimer, respectively. In order to address the relevance of multimeric species to their activities on neutrophils, analogs of NAP-2 and MGSA were synthesized in which the backbone amide proton of Leu-22 in NAP-2, and Val-26 in MGSA, was substituted with the bulky methyl group (NH --> NCH3). These analogs were shown to be monomeric by sedimentation equilibrium ultracentrifugation studies and were similar to the corresponding native protein in assays for neutrophil elastase release and Ca2+ mobilization from IL-8R1 and IL-8R2 transformed cells. Sedimentation equilibrium studies of the native NAP-2 and MGSA were also carried out to address the association behavior. For NAP-2, there was no evidence for the tetramer, but an equilibrium between monomers and dimers and the dissociation constant was calculated to be 50-100 microM. Similarly, MGSA showed a monomer-dimer equilibrium with a Kd of approximately 5 microM. The data from the monomeric analogs and also the calculation of dissociation constants indicate that NAP-2 and MGSA have a tendency to associate above the concentrations required for maximal activity or for receptor activation, but at functional concentrations they are predominantly monomers.
Chemokine CXCL1↗
Complexity of 12q13-22 amplicon in liposarcoma: microsatellite repeat analysis.
The 12q13-22 amplicon from four liposacroma specimens evaluated by comparative genomic hybridization was studied analyzing 55 microsatellite markers by PCR. All four specimens were informative in at least 34 loci; an amplification or allelic imbalance was identified with four to 17 markers. The amplicons were discontinuous; there were non-amplified marker loci between the amplified marker loci. These findings indicate the presence of separate amplicons in the 12q13-22 region. Evidence of the concomitant gain of one allele and loss of the other allele was found with several markers in one tumor and with one marker in two tumor specimens. Southern blotting showed amplification of CDK4 and MDM2 in all four specimens.
Alleles↗
Measurement of absolute cerebral haemoglobin concentration in adults and neonates.
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Adult↗
How to evaluate slow oxygenation changes to estimate absolute cerebral haemoglobin concentration by near infrared spectrophotometry in neonates.
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Brain↗
[Dosage values for characterization of patient exposure in computerized tomography and their significance for risk assessment].
In order to evaluate patients' exposure to radiation in computed tomography, dose quantities such as the computed tomography dose index (CTDI), multiple scan average dose (MSAD) and dose free in air on the axis of rotation are used. The CTDI and the MSAD, derivable from the CTDI, are a good measure for the absorbed doses in the examined volume, but they do not take the biological sensitivity of the organs into account and do not describe the radiogenic risk that is actually relevant for patients and doctors. The dose on the axis of rotation is not an accurate measure of the effective dose and the radiogenic risk. The declaration of a limit for the dose on the axis of rotation should take the different regions into account, in order to guarantee acceptable image quality on one hand and to avoid an unnecessarily high risk on the other side. As physical dose quantities, the CTDI, MSAD and dose on the axis of rotation are useful to characterize and differentiate between programs and systems concerning radiation exposure.
Humans↗
Soluble intercellular adhesion molecule-1 in patients with lung cancer and benign lung diseases.
Intercellular adhesion molecule-1 (ICAM-1) expression correlates with tumour progression in patients with malignant melanoma or renal cell carcinoma. To assess the value of soluble ICAM-1 (sICAM-1) for lung cancer patients, sICAM-1 was determined by means of an enzyme-linked immunosorbent assay. Sera from 147 patients with lung cancer, from 75 patients with benign lung diseases and from 108 healthy adults were investigated for sICAM-1 expression. Significant differences in sICAM-1 levels were detected in lung cancer patients (387 +/- 176 ng/ml) and patients with benign lung diseases (365 +/- 110 ng/ml) compared to the group of healthy adults (310 +/- 90 ng/ml). There was no difference in sICAM-1 level among the subtypes of lung cancer. Advanced tumour stages and patients with progressive disease tended to be associated with higher sICAM-1 levels, the site of metastasis being relevant for the level attained. Patients with liver metastasis had the highest sICAM-1 levels (547 +/- 295 ng/ml) compared to patients with cerebral metastasis (317.8 +/- 92.2 ng/ml). An increase of sICAM-1 expression during the progression of the disease coincided with a poorer survival prognosis for the patients compared to patients with stable or falling sICAM-1 levels.
Adolescent↗
Microsatellite markers as tools for characterization of DNA amplifications evaluated by comparative genomic hybridization.
To test the applicability of microsatellite markers in the study of DNA amplifications evaluated by comparative genomic hybridization, we analyzed 55 highly polymorphic microsatellite marker loci from six liposarcoma tumors (seven specimens) and from one atypical lipoma with a gain or high-level amplification at 12q13-22. Twelve-trisomic neoplastic cells from a patient with B-cell chronic lymphocytic leukemia were used as a positive control, in which 74% of informative loci showed allelic imbalance. In every tumor specimen microsatellite marker loci analysis showed allelic imbalance. The amplicons were discontinuous, indicating the presence of separate amplicons in the 12q13-22 region. Not only gains but also losses as well as concomitant gains and losses of alleles were observed. The use of microsatellite markers has several advantages: gene loci as well as flanking DNA loci can be analyzed, it is fast and lends itself to automation, and allows a large number of marker loci to be analyzed simultaneously.
Chromosome Mapping↗
Protein C, protein S and antithrombin III in children with portal vein obstruction.
BACKGROUND/AIMS: Portal vein obstruction is the most common single cause of portal hypertension in children and its cause is unknown in most instances. The aim of the present study was to evaluate the incidence of protein C, protein S and antithrombin III deficiencies and to screen for possible genetic deficiencies of these proteins. METHODS: A prospective study was undertaken in 20 consecutive children with portal vein obstruction, their parents and 20 matched healthy children. RESULTS: Children with portal vein obstruction displayed a reduction in protein C (p<0.05), protein S (p<0.0001), and antithrombin III (p<0.001) activities as compared with controls. Protein C and protein S activities were below 60% in nine and eleven of the children with portal vein obstruction, respectively, and antithrombin III activities were below or equal to 85% in ten of them. Repeated assay of protein C activity in seven children following a surgical portosystemic shunt showed a decrease as compared with preoperative values. Protein C, protein S and antithrombin III were normal in all parents, except two mothers in whom the levels of protein S activity and protein S antigen were found to be either below or at the lower limit of the normal range. CONCLUSIONS: These results indicate that protein C, protein S and/or antithrombin III deficiencies are frequently found in children with portal vein obstruction but are not likely to be of genetic origin in most cases.
Adolescent↗
Prognostic impact of an activation of coagulation in lung cancer.
BACKGROUND: There is evidence that activation of coagulation by influencing tumour biology may have impact on clinical course of lung cancer. PATIENTS AND METHODS: We measured the activation markers thrombin-antithrombin complex (TAT) and prothrombin fragment F1 + 2 in 99 lung cancer patients immediately after diagnosis, before antineoplastic treatment. Outcome was assessed at the end of appropriate standard primary therapy (four to six courses of chemotherapy, surgery or radiation). RESULTS AND CONCLUSIONS: The activation markers (means +/- SEM) were lower in the 33 responders (RSP; complete or partial remission) than in the 66 non-responders (NRSP): TAT 3.96 +/- 0.48 vs. 9.69 +/- 1.57 micrograms/l (P < 0.001), and F1 + 2 1.09 +/- 0.09 vs. 1.64 +/- 0.25 nmol/l (P < 0.05). TAT levels were > 6 micrograms/l in 30 of 66 (45%) NRSP, but only 4 of 33 (12%) RSP. 88% of patients with TAT < or = 6 micrograms/l achieved remission, and 45% with TAT > 6 micrograms/l (P = 0.0014). In the subgroup of 46 patients with advanced disease, the six RSP showed lower TAT than the 40 NRSP: 4.65 +/- 0.94 vs. 11.92 +/- 2.49 micrograms/l (P < 0.01); one of six (17%) RSP, but 21 of 40 (53%) NRSP showed TAT > 6 micrograms/l. These data suggest that in lung cancer the activation of coagulation is an independent prognostic factor, since TAT levels were different between RSP and NRSP, also within the homogeneously unfavourable metastatic subgroup. It should be further studied, whether TAT can identify patients, whose prognosis could be improved by anticoagulation as an adjunct to standard antineoplastic therapy.
Antithrombin III↗
Australian Leukaemia Study Group myeloma II: a randomized trial of intensive combination chemotherapy with or without interferon in patients with myeloma.
The Australian Leukaemia Study Group has performed a randomized trial of interferon alpha-2A (Roferon-A) as a co-induction agent together with intensive combination chemotherapy and as maintenance following completion of 12 cycles of induction treatment. When used as a co-induction agent, interferon-alpha did not improve response rates, time-to-treatment failure, or overall survival. Patients who had interferon together with intensive combination therapy (PCAB: prednisone 60 mg/m2 days 1-5, cyclophosphamide 600 mg/m2 day 1, BCNU 30 mg/m2 day 1, doxorubicin 30 mg/m2 day 1, repeated every 28 d for a total of 12 cycles) had more leucocyte and granulocyte toxicity and received a lower dose intensive of cytotoxic drugs than those patients who received PCAB without interferon. There was a trend towards prolongation of plateau phase which did not reach significance. Interferon, however, did improve the survival of patients who achieved plateau; for those patients interferon was associated with a 33% decrease in the rate of death after adjusting for initial beta-2 microglobulin level.
Activities of Daily Living↗
Chronic eosinophilic leukaemia (CEL): a distinct myeloproliferative disease.
Chronic eosinophilic leukaemia has not yet been clearly defined, mainly due to the fact that it has not been conclusively shown as a monoclonal disease which should be separated from chronic myelogenous leukaemia, acute myelogenous leukaemia with eosinophilia (AML, FAB M4Eo), and the idiopathic hypereosinophilic syndrome. We report a patient with a white blood cell count of 17.6 x 10(9)/l with 74% eosinophils, normal platelet count and haemoglobin. No blasts were seen in the peripheral blood and the percentage of blasts in the bone marrow was < 3%. A diagnosis of chronic eosinophilic leukaemia was made. Chromosome analysis of a bone marrow aspirate disclosed a trisomy 15 together with loss of the Y chromosome. Moreover, FISH analysis on May-Grünwald-Giemsa-stained peripheral blood smears demonstrated trisomy 15 in the eosinophils. 3 months after initial diagnosis the patient went into blast crisis and died. The blast cells exhibited trisomy 15 and loss of the Y chromosome in a complex, aberrant karyotype. In conclusion, the case shows that chronic eosinophilic leukaemia is a monoclonal, myeloproliferative disease with eosinophils as part of the malignant clone. Clinically, chronic eosinophilic leukaemia can be separated into a chronic phase and a blast crisis.
Blast Crisis↗
[How certain is teleradiological telediagnosis for the tomographic procedure?].
PURPOSE: To define the value of teleradiographic studies, a comparison was carried out between digitised copies of CT examinations of the skull with the original images. Differences in image quality obtained from a digital scanner and a camera were quantified. MATERIAL AND METHOD: 56 CT examinations of the skull, 28 of which had discrete abnormalities, were chosen for ROC analysis. The original films were digitised with a Vidar VXR-12 scanner and Panasonic WV-160 and WV-BP 500 cameras. The images were evaluated by five radiologists after image transfer with Video Conference software to a personal computer. RESULTS: For the analysis of the films the area under the ROC curve was 0.91 +/- 0.04, for the digital scanner it was 0.85 +/- 0.04, for camera WV-BP 500 0.89 +/- 0.06 and for camera WE-160 0.87 +/- 0.09. Comparison with the film findings showed. a minimal p-value of 0.17 which indicated that there was no significant reduction in diagnostic value following digitization. CONCLUSION: The probable reason for the slight deterioration using the digital scanner was the reduction to 75 dpi compared with 134 dpi on the CT films. The cameras produce image noise comparable to CT with low window settings and reduced local resolution. We expect similar results for CT with soft tissue windows or for MRT of the skull. Conventional radiographs containing high local resolution, wide grey scale and low image noise would presumably make higher demands on methods of digitization.
Computers↗
Aprotinin reduces blood loss in patients undergoing elective liver resection.
Ninety-seven patients undergoing elective liver resection through a subcostal incision were assigned to large-dose aprotinin treatment or placebo in a double-blind, prospective, randomized fashion. Randomization was stratified by diagnosis: (a) cancer in cirrhosis, (b) cancer in healthy liver, and (c) benign tumor in healthy liver. Intraoperative blood loss, percentage of transfused patients, and total transfusion requirement per group were significantly lower in the aprotinin group than in the placebo group (1217 +/- 966 mL vs 1653 +/- 1221 mL, P = 0.048; 17% vs 39%, P = 0.02; 30 vs 77 red blood cell packs, P = 0.015, respectively). Assessment of hematological markers (a) prior to surgery, (b) at the end of surgery, and (c) 24 h after surgery showed an identical intraoperative increase in thrombin-antithrombin III complexes in patients of both groups (P = 0.86), which indicates a similar activation of coagulation. Intraoperative hyperfibrinolysis was significantly less pronounced in the aprotinin group than in the placebo group (P = 0.0002 and P = 0.004 for D-dimers and fibrinogen, respectively). No adverse drug effects were detected (circulatory disturbances, deep venous thrombosis, increase in serum creatinine). These results suggest that aprotinin significantly reduces blood loss and transfusion requirement in patients undergoing elective liver resection through a subcostal incision.
Adult↗