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Biomedical subjects

M Falk

Publications and source records attributed to M Falk.

At least 55 records · Page 3Linked to original sources
PubMed1996

Epstein-Barr virus nuclear antigen 2 (EBNA2)-oestrogen receptor fusion proteins complement the EBNA2-deficient Epstein-Barr virus strain P3HR1 in transformation of primary B cells but suppress growth of human B cell lymphoma lines.

To develop a transformation system with a conditional Epstein-Barr virus nuclear antigen 2 (EBNA2) gene, we fused the hormone binding domain of the oestrogen receptor to the N or C terminus of EBNA2. In promoter transactivation as well as primary B cell transformation assays these chimeric EBNA2 proteins are able to substitute for wild-type EBNA2 in the presence of oestrogen. Here we provide evidence that this transformation is the result of double infection of a cell with two virions, the P3HR1 virus genome and a mini-EBV plasmid carrying the chimeric EBNA2 gene. Unexpectedly, expression of the same EBNA2-oestrogen receptor fusion protein in established human B cell lymphoma lines resulted in growth retardation or growth arrest upon the addition of oestrogen. By titrating the oestrogen concentration in these stably transfected cells, the growth retarding and the transactivating function of the chimeric proteins could not be dissociated. We propose that growth inhibition of established B cell lymphoma lines is a novel function of EBNA2 which has not been detected in the absence of an inducible system. It remains open whether the growth retarding property of the EBNA2-oestrogen receptor fusion protein in B cell lymphoma lines is due to unphysiologically high expression of the chimeric protein or to interference with a cellular programme driving proliferation in these cell lines.

Antigens, Viral↗
PubMed1996

Early sensitization to farming-related antigens among young farmers: analysis of risk factors.

It was the aim of this study to investigate the prevalence of and risk factors for IgE- and IgG-mediated allergy in young farmers. We investigated 147 young men attending a farming college in the Austrian Tyrol and 57 age-matched pupils at a grammar school. All individuals completed a questionnaire and had spirometry, skin prick tests, total and specific IgE analysis, and testing for precipitins against thermophilic actinomycetes and true fungi. In the farming group, a family history of atopy or asthma was reported less frequently than in the control group (p < 0.001) but there were no differences in the frequencies of actual respiratory symptoms. Forced expiratory volume in the first second (FEV1) was slightly lower in the farmers than in the pupils (p < 0.05). There was no difference in the prevalence of IgE-mediated allergy. Nine of the farmers but none of the pupils had precipitating antibodies against Faeni rectivirgula (p < 0.05). Overall reactivity (as defined by at least one positive finding with the skin prick test, specific IgE, or precipitins) was associated with larger farming estates, lack of a haydrying device, use of mouldy hay, and positive family history of asthma (p < 0.05). We conclude that in farmers, precipitin formation may occur at an early age and that even in younger age groups there is a clear relationship between allergic sensitization and occupational allergen exposure.

Adolescent↗
PubMed1996

Cost-benefit analysis of diabetic eye disease.

Diabetic retinopathy is the main cause of blindness in adults 25-74 years of age in Western countries. At 100% diagnosability and 100% treatability, with laser photocoagulation vision can be retained in at least one eye in 73% of patients with proliferative retinopathy and in 67% of patients with diabetic maculopathy. The cost-benefit analysis draws a comparison of the costs incurred through benefits granted to a blind diabetic and those incurred through proper screening, examination and treatment to avoid blindness as much as possible. These calculations are valid for the State of Tyrol in Austria. The anticipated annual costs for blindness are thus ATS 19,000,000, of which ATS 14,600,000 could be avoided through an optimal screening, examination and therapy program. The maximum costs for examination and therapy amount to ATS 10,700,000, thus giving a minimum saving of ATS 3,900,000 in favor of preventive medicine.

Adult↗
PubMed1996

CEOP-IMVP-Dexa in the treatment of aggressive lymphomas: an Austrian multicenter trial.

PURPOSE: This trial evaluated the efficacy, toxicity, and practicability of a new intensive chemotherapy regimen in a multicenter setting of university and community hospitals. PATIENTS AND METHODS: We tested a hybrid protocol of two non-cross-resistant regimens, cyclophosphamide, epirubicin, vincristine, and prednisolone (CEOP) and ifosfamide, etoposide (VP-16), methotrexate, and dexamethasone (IMVP-Dexa) given every fourth week, three to six times according to response, in patients with untreated intermediate- and high-grade non-Hodgkin's lymphoma. Ten Austrian centers entered 81 patients onto this multicenter trial. Eleven patients were excluded. The median age was 55 years. Twenty-six of 70 patients had stage III or IV disease. The distribution among international risk categories low, intermediate-low, intermediate-high, and high was 20%, 34%, 23%, and 23%, respectively. RESULTS: Of 70 eligible patients, 56 (80%) had a complete remission and seven (10%) a partial remission. After a median observation time of 36 months, the estimated time to relapse and overall survival rates are 67% and 72%, respectively. Age and Karnofsky index were the only independent risk factors for survival. Toxicity was primarily hematologic, with a median granulocyte nadir of 0.56 x 10(9)/L. Sixty-seven percent of patients had infections; 25.7% were severe World Health Organization (WHO) grade III or IV. There were three treatment-related deaths. CONCLUSION: CEOP-IMVP-Dexa chemotherapy is safe and feasible on a groupwide basis even when used in community hospitals. Neutropenic infections are the major complications. A 72% 3-year survival rate in patients with intermediate- and high-grade non-Hodgkin's lymphoma warrants further studies. These data are the basis for a randomized trial to compare cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with CEOP/IMVP-Dexa.

Adolescent↗
PubMed1996

Integrin alpha 6B beta 1 is involved in kidney tubulogenesis in vitro.

Laminin-1 has previously been shown to be of major importance for the development of kidney tubules. Antibodies against fragments E8 and E3 of laminin-1 perturb kidney development in vitro. We here studied expression of integrins alpha 6 beta 1 and alpha 6 beta 4, two known laminin receptors, during kidney development. Integrin beta 1 subunit could be detected by immunofluorescence on all cell types of embryonic mouse kidney, but we could not detect integrin beta 4 subunit in embryonic kidney by immunofluorescence or by in situ hybridization. The presence of integrin alpha 6 subunit in all epithelia of embryonic kidney was demonstrated by immunofluorescence and by in situ hybridization. RT-PCR showed that alpha 6B is the major splice variant in embryonic kidney. During in vitro conversion of nephrogenic mesenchyme to epithelial tubules, a strong increase in the expression of the 6 kb mRNA for alpha 6 integrin subunit was seen by northern blotting at the onset of epithelial morphogenesis, on day two of culture. Immunoprecipitation of extracts from embryonic kidney with antibodies against alpha 6 subunit yielded bands corresponding to the expected size of beta 1 integrin subunit but not of beta 4 subunit. Monoclonal antibodies against either alpha 6 or beta 1 subunit but not against E-cadherin blocked kidney tubulogenesis in vitro. This suggests that integrin alpha 6B beta 1 is involved in kidney tubulogenesis in vitro. Another possibility is that the antibodies against integrin alpha 6 and beta 1 subunit cause abnormal signalling by the integrin.

Animals↗
PubMed1995

Cardiac troponin T and creatine kinase MB mass concentrations in children receiving anthracycline chemotherapy.

Anthracyclines (doxorubicin, daunorubicin, and derivatives) are among the most effective antineoplastic drugs for pediatric cancer with dose-limiting acute and long-term cardiotoxicity. The exact mechanism of the development of cardiomyopathy is still not clear. Anthracyclines may induce subclinical acute myocardial injury leading to lysis of a limited number of myocytes. Alternatively, myocytes may experience a transient loss of cytoplasmic membrane integrity. Both conditions may lead to a transient efflux of small amounts of cytoplasmic enzymes and other proteins specific to the heart muscle fibers. To test these hypotheses we assayed plasma creatine kinase (CK) MB mass and cardiac specific troponin T (TnT). CKMB may be released even in case of reversible cell membrane injury, while prolonged elevation of TnT is the most sensitive and specific marker of limited myocardial necrosis. Thirty-five anthracycline-containing chemotherapy courses in 22 children with cancer were analyzed. CKMB mass and TnT concentrations were within the normal range in all children before anthracycline therapy. Within 72 hours from anthracycline therapy no increment of one of these two marker proteins was detected (ANOVA for repeated measures, P = 0.94 [TnT] and 0.25 [CKMB]). We conclude that only minimal if any acute necroses of cardiac myocytes occur after anthracycline therapy. Even membrane integrity appears to be maintained within the first 3 days after anthracycline therapy, in the absence of electrocardiographic or echocardiographic signs of acute cardiotoxicity.

Adolescent↗
PubMed1995

Recombinant human granulocyte-macrophage colony-stimulating factor in septic neutropenic pediatric cancer patients: detection of circulating hematopoietic precursor cells correlates with rapid granulocyte recovery.

Cycling intensive chemotherapy currently used to treat pediatric solid tumors induces severe neutropenia. Prolonged neutropenia is a major risk factor for septic death which occurs in up to 5% of febrile or septic neutropenic episodes. We treated 18 neutropenic pediatric cancer patients (eight females, 10 males) during 30 febrile and/or septic episodes with single daily doses of E. coli-derived non-glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rh-GM-CSF, 5 micrograms per kg of body weight). The cytokine was administered for a median period of 6.5 days (2-12 days). Analysis of circulating hematopoietic progenitor cells was performed at day 1 (baseline) and day 5 of rh-GM-CSF treatment and included flow cytometric CD34 analysis as well as the methylcellulose-based clonogenic assay. Prompt hematopoietic recovery and resolution of septic problems was observed in all children. The counts of leukocytes (WBC), absolute neutrophils (ANC), and platelets (PLT) rose above 1,000/microL, 1,000/microL, and 50,000/microL within 4 days (0-9), 5.5 days (2-13), and 6 days (0-14), respectively. Faster granulocyte recovery and improved recruitment of circulating hemopoietic precursors was observed in children with detectable amounts (> 0.1%) of CD34-positive mononuclear cells prior to rh-GM-CSF treatment. We conclude that, to some extent, the efficacy of rh-GM-CSF treatment in neutropenic cancer patients is influenced by the hematopoietic recovery status on the progenitor cell level. Although they respond more slowly to the treatment, patients without circulating CD34-positive progenitor cells may gain most from growth factor therapy. Rh-GM-CSF can be safely administered to febrile and/or septic neutropenic children treated for cancer.

Adolescent↗
PubMed1995

Effect of age and disease duration on parkinsonian motor scores under levodopa therapy.

One hundred and fifty patients suffering from Parkinson's disease were analysed for the expression of the motor symptoms during optimum response to levodopa therapy (subscale III of the Unified-Parkinson's Disease Rating Scale). Patients were grouped according to age (< or = 64, 65-74, > or = 75 years). Disease duration and daily levodopa dosage were similar in the three groups. Pooled residual scores for posture and gait impairment (PGI), tremor (T), rigidity (R) and distal motor impairment (DMI; hand and foot movements) increased with age (Kruskal-Wallis ANOVA). The parkinsonian scores were significantly higher than the scores of 150 age-matched normal controls (Mann-Whitney U test). The differences between the patients' scores and the scores of the age-matched controls increased with age. In spite of a significant increase in the daily levodopa dosage with disease duration (linear regression), PGI aggravated age-dependently, and DMI age-independently with symptom duration (Spearman rank correlation). In contrast, T and R did not increase with disease duration.

Adult↗
PubMed1995

Influence of serum lipid fractions on the course of diabetic macular edema after photocoagulation.

The influence of serum lipid fractions [triglyceride, cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol] on the visual outcome after central laser photocoagulation of 39 patients (65 eyes) with clinically significant macular edema was investigated in a prospective study. Referring to normal Austrian serum lipid levels, the patients were classified into a normal and a pathological group for each of the 4 lipids. Concerning triglycerides and HDL cholesterol, the normal group (triglyceride < 2.29 mmol/l, HDL cholesterol > 1.3 mmol/l) showed a statistically significantly better visual outcome than the pathological group. Also, patients with normal total cholesterol and LDL cholesterol values tended to achieve better results after treatment. We therefore conclude that serum lipid fractions may influence not only the success of laser treatment but also the course of diabetic macular edema.

Adult↗
PubMed1995

Humoral response to Plasmodium falciparum ring-infected erythrocyte surface antigen in a highly endemic area of Papua New Guinea.

The prevalence and concentration of antibodies to ring-infected erythrocyte surface antigen (RESA) were measured in blood samples collected during a cross-sectional survey conducted in Papua New Guinea. Antibodies were measured by enzyme-linked immunosorbent assay to the recombinant RESA protein in 1,398 subjects and to RESA 8 and RESA 11 synthetic peptides in a subsample of 200 adults. Overall, the seropositivity rate to recombinant RESA was 66% and the geometric mean antibody concentration was 28 micrograms/ml. There was a slow increase in antibody prevalence and concentration with age that continued to occur even after 40 years of age. In children less than 10 years of age, there was a significant positive correlation between both RESA antibody prevalence and concentration and concurrent infection with Plasmodium falciparum. The opposite was true in adults more than 20 years of age, with those having a high antibody concentration to RESA being less likely to be parasitemic at the time of the survey. This observation was consistent with the finding of a weak but significant negative correlation between log antibody concentration and log P. falciparum density, which was mainly found in adults. No consistent correlation was found between humoral immune response to RESA and morbidity indicators.

Adolescent↗
PubMed1995

A comparison of five methods of temperature measurement in febrile intensive care patients.

BACKGROUND: A clinically useful temperature measurement method should correlate well with the body's core temperature. Although previous investigators have studied temperature readings from different sites in hypothermic and normothermic patients, none have compared methods specifically in febrile patients. OBJECTIVE: To compare temperature measurement methods in febrile intensive care patients. METHODS: Temperature readings were obtained in rapid sequence from an electronic thermometer for oral and axillary temperature, rectal probe, infrared ear thermometer on "core" setting, and pulmonary artery catheter, approximately every hour during the day and every 4 hours at night. The sample consisted of 13 patients with pulmonary artery catheters and with temperatures of at least 37.8 degrees C. RESULTS: Rectal temperature correlated most closely with pulmonary artery temperature. Rectal temperature showed closest agreement with pulmonary artery temperature, followed by oral, ear-based, and axillary temperatures. Rectal and ear-based temperatures were most sensitive in detecting temperatures greater than 38.3 degrees C. Likelihood ratios for detecting hyperthermia were 5.32 for oral, 2.46 for rectal, and 1.97 for ear-based temperature. Rectal and ear-based temperatures had the lowest negative likelihood ratios, indicating the least chance of a false negative reading. Axillary temperature had a negative likelihood ratio of 0.86. CONCLUSIONS: Rectal temperature measurement correlates most closely with core temperature. If the rectal site is contraindicated, oral or ear-based temperatures are acceptable. Axillary temperature does not correlate well with pulmonary artery temperature. These results underscore the importance of consistency in method when establishing temperature trends, and of awareness of method when interpreting clinical data.

Adult↗
PubMed1995

The risk of urethral tumors in female bladder cancer: can the urethra be used for orthotopic reconstruction of the lower urinary tract?

We studied the risk of synchronous or secondary urethral tumors after long-term followup in women with bladder cancer. The charts of women treated for various stages of bladder cancer between 1973 and 1992 were reviewed. Of 356 evaluable patients 268 presented initially with primary and 78 with multilocular tumor involvement. There were 498 episodes of recurrent tumors in 127 patients, and a total 1,210 tumor locations in 854 primary and recurrent episodes of bladder cancer. Mean followup for these patients was 5.5 years (range 0.05 to 33.1). Overall 7 of 356 patients (2%) had urethral tumor involvement, all at initial presentation. Statistical comparison of various defined tumor localizations in the bladder revealed that the bladder neck (p < 0.000) and trigone (p < 0.035) were significantly more often the region of primary tumor occurrence in the urethral tumor group. All patients with secondary urethral tumors had tumor involvement of the bladder neck at the same time. A 1% urethral tumor involvement was seen among 104 patients with clinical stage T2 to 3b, N0, M0 transitional cell carcinoma, who could have been considered for curative radical cystectomy. No patient presenting with tumor recurrence regardless of its location was found to have urethral tumors. Subtotal urethrectomy is an option in select female patients after cystectomy for localized bladder cancer to allow orthotopic reconstruction of the lower urinary tract provided the bladder neck is free of tumor.

Adult↗
PubMed1995

Identification of a favorable subgroup of patients with generalized immunocytomas by follicular dendritic cells.

In the present study, 89 patients with generalized immunocytoma were analyzed retrospectively for the prognostic influence of clinical features and of immunophenotype using bone marrow biopsies. Univariate analysis selected the following variables as significant for survival: age over 60 years (p = 0.021), Rai and Binet stage (p = 0.008 and 0.004, respectively), presence or absence of follicular dendritic cells (FDC, p = 0.036), presence or absence of anemia (p = 0.037). Multivariate regression analysis showed independent prognostic significance of age (p = 0.001), Rai stage (p = 0.003), and the presence of follicular dendritic cells (p = 0.010). Comparing CD5 positive and CD5 negative immunocytomas, no survival advantage for one of the two groups was seen. Presence of follicular dendritic cells clearly identified a favorable prognostic subgroup: of the 89 patients presented, only three of 18 (16.6%) with detectable FDC in bone marrow died within the observation period, as compared to 34 of 71 (52.1%) patients without FDC. Multivariate analysis emphasized the independent prognostic value of the presence of FDC. The high predictive capacity of follicular dendritic cells could add useful information to the commonly used Rai and Binet staging systems for immunocytoma.

Adult↗
PubMed1994

Establishment of two permanent human bone marrow stromal cell lines with long-term post irradiation feeder capacity.

We describe the establishment of two permanent Simian virus 40-transformed human stromal cell lines, designated L87/4 and L88/5, derived from the bone marrow of a hematologically normal male patient. Both cell lines show a fibroblastoid morphology and do not express hematopoietic cell markers. L87/4 but not L88/5 expresses the macrophage marker CD68. The most remarkable feature of these new stromal cell lines is their ability to persist as growth-arrested adherent feeder cells after ionizing-irradiation at doses up to, and exceeding 20 Gy (L87/4). This renders them particularly useful for studying aspects of feeder dependence of hematopoietic cell development in long-term culture. Both cell lines are able to function as feeder cells, supporting the long-term proliferation of CD34+ human cord blood cells as well as the clonogenic growth of the human Burkitt lymphoma B-cell line BL70.

Bone Marrow Cells↗
PubMed1994

Assessment of the alcohol withdrawal syndrome--validity and reliability of the translated and modified Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-A).

The alcohol withdrawal syndrome is a common phenomenon in psychiatric hospital care. Not only treatment strategies, but also the evaluation of the syndrome, are discussed controversially. The most widely used instrument is the Clinical Institute Withdrawal Assessment-Alcohol (CIWA-A) and the succeeding CIWA-Ar. We modified the CIWA-A and translated it into German. Validity and reliability of the modified and translated scale were analysed by several psychological tests as well as different somatic measures in 31 patients. The German version appears to be a valid and reliable instrument for the assessment of alcohol withdrawal syndrome useful for clinical routine as well as treatment trials.

Alcohol Withdrawal Delirium↗
PubMed1994

Dopamine and mucosal oxygenation in the porcine jejunum.

The effect of intravenously delivered dopamine on jejunal tissue oxygenation was studied in 12 pigs anesthetized with midazolam and sufentanil and mechanically ventilated. A small segment of the jejunal mucosa and serosa was exposed by midline laparotomy and antimesenteric incision. Mucosal and serosal tissue PO2, mucosal microvascular hemoglobin oxygen saturation, and mucosal hemoglobin concentration were measured by means of Clark-type oxygen electrodes and tissue reflectance spectrophotometry, respectively. In five animals electromyogenic potentials of the jejunal wall were recorded. Measurements were performed under baseline conditions and after intravenous infusion of 2, 4, 8, 16, 32, and again 2 micrograms.kg-1.min-1 of dopamine. The drug produced a dose-related increase in mucosal PO2 (from 26.5 Torr at baseline to 49 Torr at 32 micrograms of dopamine; P < 0.001) and mucosal hemoglobin oxygen saturation (from 55.1 to 70.1%; P < 0.03) but no change in serosal PO2 (from 70.6 to 65.5 Torr). In nine animals baseline mucosal PO2 and mucosal hemoglobin oxygen saturation showed rhythmic oscillations with a frequency of 2.5-5 cycles/min that could not be related to electromyogenic potentials. Dopamine decreased the oscillation amplitude of these two parameters (P < 0.001), and at doses > 16 micrograms.kg-1.min-1 they were no longer present. Dopamine therefore improves mucosal oxygenation of the porcine jejunum in a selective and dose-related manner. At higher doses the preexisting oscillatory pattern of mucosal oxygenation, which is most likely due to vasomotion, is impeded.

Animals↗
PubMed1994

Endothelin and atrial natriuretic peptide in non-insulin-dependent diabetic versus nondiabetic patients on chronic hemodialysis.

Plasma levels of endothelin (ET) and atrial natriuretic peptide (ANP) are known to be elevated in patients on chronic hemodialysis. Since ET and ANP plasma levels are found to be raised in nonuremic diabetic versus nondiabetic subjects, we wanted to detect a possible difference in plasma levels of these hormones in diabetic versus nondiabetic patients who were on chronic renal replacement therapy. ET is a possible marker of increased vascular atherogenic activity. We measured plasma levels of ET and ANP pre- and posthemodialysis in 23 non-insulin-dependent (NIDDM) diabetic versus 23 nondiabetic patients who were matched according to age and time of day of hemodialysis, and who did not show clinical signs of overt cardiac decompensation. Mean plasma levels of ET and ANP did not differ in diabetic from nondiabetic patients, neither pre- nor postdialysis. In both patient groups, mean ET levels were twice the upper normal limit, did not change significantly pre- versus postdialysis, and did not correlate with blood pressure or with volume ultrafiltration during dialysis. Calcium channel blocker therapy was accompanied by a significant rise of ET pre- and postdialysis in nondiabetic patients but not in diabetic patients. In diabetic patients, ET plasma levels correlated positively with fructosamine levels as an indicator of short-term blood glucose control. Mean ANP plasma levels were about three times the upper normal limit and decreased significantly during dialysis, but this decrease correlated neither with volume ultrafiltration nor with blood pressure. In conclusion, we could not find a difference in plasma levels of ET and ANP for diabetic versus nondiabetic dialysis patients, but impaired short-term blood glucose control in diabetic and calcium channel blocker therapy in only nondiabetic dialysis patients showed concomitant increases in plasma ET levels and thus possibly different mechanisms of ET regulating pathways.

Aged↗