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M Tschan

Publications and source records attributed to M Tschan.

13 recordsLinked to original sources

Divergent expression of cyclin-dependent kinase inhibitors (CKI) and p14ARF/p16 beta in non-Hodgkin's lymphomas and chronic lymphocytic leukemia.

Chronic B-cell lymphocytic leukaemia (CLL) and low-grade B-cell Non Hodgkin's lymphomas (Lg-NHL) are characterized by slow accumulation of neoplastic cells arrested in the G0/G1 phase of the cell cycle. In contrast, proliferation rates are high in aggressive B-cell lymphomas (Hg-NHL). Divergent expression of cyclin-dependent kinase inhibitors (CKI) in the cell cycle may contribute to these differences. We analysed CLL as well as low and high grade B-cell NHL for expression of G1-specific and universal CKI by competitive RT-PCR and immunostaining. p16(INK4A) expression was low in all types of neoplasms. Highest p14(ARF) /p16 beta expression levels were found in normal lymphocytes. Expression of this CKI was significantly lower in CLL, but still higher in CLL than in the lymphomas (median 27 vs. 3 mRNA transcripts x 10(3), p = 0.0001). p14(ARF) /p16 beta immunostaining correlated with mRNA expression. Highest p21 mRNA levels were found in CLL, but three of four CLL with abundant p21 mRNA production were negative on immunostaining. High grade lymphomas showed markedly decreased p21 expression (3.9 in Hg-NHL vs. 12 in Lg-NHL and 29 in CLL; values expressed as mRNA transcripts x 10(3), p < 0.009). mRNA and protein expression of p27 was considerably higher in CLL than in the lymphomas. Differential CKI expression in various B-cell neoplasias may provide important biological markers, if not the molecular underpinning of their different cell cycle kinetics. Targeted interference with such genes governing cell cycle control in lymphoid neoplasia may pave the way towards new treatment strategies.

Adult↗

Aberrant FHIT mRNA transcripts are present in malignant and normal haematopoiesis, but absence of FHIT protein is restricted to leukaemia.

Aberrant FHIT mRNA transcripts are present in malignant and normal haematopoiesis, but absence of FHIT protein is restricted to leukaemia Alterations of the recently cloned fragile histidine triad (FHIT) gene at chromosome 3p14.2 are frequent in a variety of solid tumours and cancer cell lines. Based on these findings, FHIT has been proposed as a putative tumour-suppressor gene. We evaluated the mRNA expression of the FHIT gene in samples from 55 patients with various haematological malignancies (21 AML, 8 CML, 10 CLL, seven low-grade and nine high-grade Non-Hodgkin's lymphomas), in a panel of 16 leukaemia cell lines, in normal mature haematopoietic cells of both myeloid and lymphoid lineage, as well as in CD34+ haematopoietic progenitor cells. Aberrant FHIT mRNA transcripts were observed in 14/16 (88%) leukaemia cell lines, 43/55 (78%) primary haematological neoplasms, but also in 17/22 (77%) normal controls. 1/16 (6%) cell lines and 7/55 (13%) neoplasms did not express any FHIT mRNA. cDNA sequencing revealed exonic deletions, small DNA insertions and combinations of both. Analysis of genomic DNA showed gene deletions in two myeloid leukaemia cell lines. In contrast to all normal types of haematopoietic cells, FHIT protein was clearly reduced or absent in 8/18 (44%) neoplastic samples tested. Our data indicate that whilst aberrant FHIT mRNA transcripts are seen both in normal and malignant cells, lack of FHIT protein is restricted to leukaemia. Absent FHIT protein expression might contribute to leukaemogenesis.

Acid Anhydride Hydrolases↗

[Complications of bronchoscopy].

1500 bronchoscopies performed in the Department of Pneumology, University of Basle, were analyzed for frequency and severity of complications. 500 patients were investigated by rigid tube in local anesthesia, 500 patients by rigid tube in neuroleptanalgesia and 500 patients by flexible fiberbronchoscope. The rate of complication for all patients was 4.1%, which agrees well with the previously reported complication frequency of 1-11%. The complications were minor in 3.5% of patients, moderate in 0.5% and major in 0.1%. There were no deaths. The incidence of severe complications and deaths was thus lower than in other studies. There was a higher incidence of complications (p less than 0.001) in the group examined with the rigid tube in neuroleptanalgesia, due to the more frequently observed minor complications. The incidence of complications can be reduced by a careful indication for bronchoscopy, adequate yet sparing use of anesthesia, and choice of the right instrument.

Adolescent↗

Theophylline serum concentration and therapeutic effect in severe acute bronchial obstruction: the optimal use of intravenously administered aminophylline.

In 20 patients with acute exacerbation of bronchial obstruction, the therapeutic effect of high (20 mg/L) and low (10 mg/L) serum concentrations of theophylline was compared in a double-blind randomized study. The theophylline dose, administered as a continuous aminophylline infusion, was individually adjusted by means of repeated measurements of serum concentrations. At 28 h after starting therapy the high concentration group showed a significantly greater improvement in pulmonary function as assessed by FEV1 (0.57 +/- 0.52 L (mean +/- SD) versus 0.1 +/- 0.18 L, p less than 0.01) and FVC (1.0 +/- 0.65 L versus 0.01 +/- 0.66 L, p less than 0.02). As a measure of the overall clinical improvement, the time during which intravenous therapy was required was also shorter in the high-dose group (61.7 +/- 25.8 h (mean +/- SD) versus 116 +/- 49.7 h, p less than 0.02). The occurrence of side effects in the two groups was not significantly different. In patients with severe acute bronchial obstruction, serum theophylline concentrations around 20 mg/L seemed to offer a definite therapeutic advantage, thus, routine serum concentration measurements and the use of accurate infusion devices for optimal dose adjustment may be justified.

Adult↗

[Rehabilitation program with IPPB-home treatment in severe chronic obstructive lung disease: hospitalizations and cost analysis].

31 patients with severe chronic obstructive lung disease (FEV1 less than 45% VC) were included in a rehabilitation program with IPPB home care. The frequency and duration of hospitalizations in the three years before and the three years following institution of the program were compared. During the rehabilitation period the incidence of hospitalizations fell from 87 to 46 (p less than 0.001), and the number of days spent in hospital decreased from 2896 to 1099 (p less than 0.001). The high cost of the rehabilitation program requires careful selection and competent instruction of candidates. If these basic requirements are observed, a surprising reduction in the total cost of treatment can be achieved by shortening the expensive hospital stay.

Cost Control↗

Dose response relationship of clenbuterol (NAB 365) as a solution for inhalation.

The dose-response relationship of the new bronchodilator Clenbuterol (NAB 365, Boehringer Ingelheim) was tested in 12 patients with chronic obstructive lung disease. Clenbuterol is a beta-2-sympathicomimetic, from a series of substituted phenylethanolamines, and it is characterised by good absorption and prolonged action after systemic administration. The action of four different doses of Clenbuterol inhalation solution (6, 12, 24, and 48 microgram corresponding to 2, 4, 8 and 16 drops of a 0.006% solution) was assessed after a single inhalation on 4 successive days. The parameters monitored were bronchial resistance and FEV. The effect of all four doses was the same, both in respect of improvement in FEV and of decrease in bronchial resistance. The increase in expiratory volume and the decrease in bronchial resistance lasted for 6 h. The results show that for inhalation therapy Clenbuterol is a potent, selective bronchodilator, which is largely free of sideeffects. It has still to be determined whether a maximal effect could be achieved with a lower dose 6 microgram.

Adult↗

[Procedure on finding microhematuria in medical practice].

Of 2000 unselected patients consecutively examined during the first 3 months of 1972 at the Outpatient Clinic for Internal Medicine, University of Basel, 102 (5.1%) were found to have pathologic erythrocyturia on routine urinalysis. In 63 of these patients the first examination did not produce a precise diagnosis such as to explain the microhematuria symptom. 30 of the 63 patients were not rechecked. 24 of the 33 rechecked patients with microhematuria again showed a pathologic erythrocyte count in urinalysis. Further workup for hematuria in 18 of these patients produced a definite diagnosis in 11 but not in the other 7 i.e. the final diagnosis in the latter was (microhematuria of undetermined origin). Workup for microhematuria is of great importance in clinical practice, and for this reason a specific procedure for workup of ambulatory patients is proposed.

Anticoagulants↗