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Biomedical subjects

W Hoffmann

Publications and source records attributed to W Hoffmann.

At least 199 records · Page 11Linked to original sources

[Beta blockade with celiprolol in tardive dyskinesia patients treated with neuroleptics].

The influence of celiprolol on the symptoms of tardive dyskinesia was compared with placebo in a randomized double blind study. 17 female patients were treated with a single daily dose of 200 mg celiprolol and 18 female patients received placebo for a period of 3 months. All patients got additional neuroleptic treatment. Celiprolol produced a small decrease in heart rate and systolic blood pressure, but had no influence on the diastolic blood pressure. The effects of celiprolol on the symptoms of tardive dyskinesia were similar to those of the placebo; in both groups improvements and deteriorations were observed. One patient of the celiprolol group became symptom free. Two cases of collapse occurred after 10 weeks of treatment with celiprolol. In one case collapse was associated with diarrhoea, in the other case the patient had preexisting hypotensive circulatory dysregulation. Sporadic reports about the effect of propranolol in patients with tardive dyskinesia might reflect the normal progress of the disease or the effect might depend on the different pharmacological profile of propranolol.

Adult↗

Results of the Austrian celiprolol postmarketing surveillance study.

This study was initiated to assess the efficacy and safety of celiprolol in a large number of hypertensive patients. Patients received a once-daily dose of 200 mg celiprolol for the first 3 weeks. If blood pressure was not lowered satisfactorily, the investigator was asked to raise the dose to 300 mg celiprolol or add a diuretic for the next 3 weeks. The study included 2,694 patients, 2,311 of whom were evaluable over a period of 3 weeks, 1,876 over 6 weeks. On admission 10% had isolated systolic hypertension, 38% mild diastolic hypertension, 35% moderate diastolic hypertension, and 17% severe diastolic hypertension. Concomitant diseases were diabetes mellitus, chronic obstructive airway disease, and peripheral arterial disease. BP was lowered in patients with hypertension of all degrees of severity. There was no obvious relation between efficacy and age or with duration of disease. Only 229 patients received 300 mg celiprolol; 223 patients additionally received a diuretic. Heart rate decreased by a mean of 8 beats/min and was lowered mostly in patients with tachycardia. In no case did heart rate fall below 50. Side effects were rare and in most cases not serious. Treatment was discontinued owing to suspected adverse effects in 58 patients (2.15%). In conclusion, celiprolol administered for up to 6 weeks appeared to be safe in the management of hypertension.

Celiprolol↗

Bone marrow transplantation in severe aplastic anemia and acute or chronic leukemia.

In Essen 121 bone marrow transplantations were carried out. The indications were severe aplastic anemia (n = 18), acute leukemia in relapse (n = 20), acute leukemia in remission (n = 46) or chronic myeloid leukemia (n = 37). The conditioning regimen consisted of cyclophosphamide or the combination of cyclophosphamide and total body irradiation. All patients were treated under strict gnotobiotic care. To mitigate the risk of CMV infections intravenous CMV-hyperimmunoglobulin and CMV-negative blood products have been applied routinely since two years. MTX was used as prophylaxis against GVH-disease. In case of severe aplastic anemia 13 patients (72%) are still alive with a median observation time of 24 months. In the prognostically unfavourable group of acute leukemia in relapse only one patient showed long term survival. In this patient leukemic relapse occurred six years after transplantation. The survival rate of AML patients grafted during the first remission is 55% (15/27) with a median observation time of 40 months. For patients grafted in first or consecutive remission of ALL the survival rate is 42% (5/12) with a maximal observation time of 29 months. Out of 37 patients grafted because of CML, eight were in an advanced stage of the disease. 13 patients are still alive, the maximal observation time is 37 months. The overall incidence of GVHD in patients at risk was 28% in aplastic anemia, 26% in AML, 9% in ALL and 63% in CML. In aplastic anemia no patient developed an interstitial pneumonia. In leukemia the risk of fatal interstitial pneumonia was 34%.

Acute Disease↗

Molecular characterization of the CAN1 locus in Saccharomyces cerevisiae. A transmembrane protein without N-terminal hydrophobic signal sequence.

The complete DNA sequence of the CAN1 locus of the yeast Saccharomyces cerevisiae is presented. The predicted primary translation product consists of 590 amino acids. From the hydropathic profile of the amino acid sequence (as calculated by the algorithm of Kyte and Doolittle (Kyte, J., and Doolittle, R. F. (1982) J. Mol. Biol. 157, 105-132)), one can divide the protein into two distinct regions. The 93-amino acid long N-terminal domain is extremely hydrophilic and does not exhibit any cleavable signal sequence. The rest of the protein (from amino acids 94 to 590) shows features typical for an integral membrane protein. The proposal for the N terminus of the primary translation product is based on results obtained by S1 mapping, insertion mutagenesis, and gene fusion experiments.

Amino Acid Sequence↗

[A method of computer-assisted evaluation of programmed single stimulation for determination of sinoatrial conduction time].

The determination of the sino-atrial conduction time by means of premature individual atrial stimulation is an important partial function in the intracardial sino-atrial functional test and a reasonable parameter in selected diagnostic questions for the clarification of syncopic conditions under suspicion of a sick-sinus syndrome. In order to alleviate the clinical use and to reduce the considerable expenditure of time in the calculation of the results for the determination of the sino-atrial conduction time by about 60% a computerized evaluation method was elaborated. This methodology resulted in an exoneration from the manual graphic-calculatory expenditure and in comparison to the traditional calculation method it did not show any statistically significant differences.

Computers↗

Amino acid sequence microheterogeneities of basic (type II) cytokeratins of Xenopus laevis epidermis and evolutionary conservativity of helical and non-helical domains.

Three clones coding for carboxy-terminal portions of type II cytokeratins have been isolated from a cDNA library constructed from the epidermis of the frog Xenopus laevis. These clones have been identified by hybridization-selection-translation and Northern blot analysis, and contain sequences complementary to mRNAs of similar size that code for three different polypeptides of the Mr 64,000 group, Ia-c, i.e. the only major type II cytokeratins expressed in this tissue. A comparison of the corresponding nucleotide sequences and the amino acid sequences deduced therefrom shows only minor differences in these polypeptides, most of which occur as isolated point mutations. This indicates that coding sequences of the different type II cytokeratin genes in epidermis of Xenopus are very similar, in contrast to the more extended differences of type II cytokeratin genes expressed in mammalian epidermis, which probably reflects a lower degree of evolutionary divergence of members of this protein family in amphibia. A comparison of the Xenopus sequences with those of mammalian type II cytokeratins reveals the same characteristic features, i.e. an alpha-helical domain ending with the familiar consensus sequence T Y R (X Y) L E G E, followed by a non-helical domain Cl enriched in hydroxyamino acids. Both domains are remarkably conserved in sequence between Xenopus and mammals. The following glycine-rich domain (C2) displays similar oligopeptide repeats (mostly of the type G G G M in the frog keratins), and the terminal C3 domain is characterized by a region exceptionally rich in hydroxyamino acids, which immediately precedes a cluster of basic amino acids at the carboxy terminus. Our results show that the typical features of the domain of type II cytokeratins are already established in amphibia and that these homologies are not restricted to the alpha-helical rod of these proteins but, in principle, extend to the other domains located in the so-called hypervariable tail portion. This suggests that the hypervariable regions are not subject to random variability but contain functionally important domains that have been well conserved during evolution.

Amino Acid Sequence↗

[Treatment of hypertension with a new beta blocker-diuretic combination under long-term control].

161 hospitalized hypertensive patients of all degrees of severity were treated with a dose of once daily 200 mg celiprolol for 3 weeks. The data of 143 patients were evaluated. After 3 weeks of therapy with 200 mg celiprolol 67,8% of the patients showed to be responders. 42 non responders were treated under double blind conditions for the following 3 weeks with 2 different dosages of chlorthalidone (12,5 mg or 25 mg CT) in combination with 200 mg celiprolol once daily. After 3 weeks of therapy 80,9% of the patients showed a satisfying reduction of blood pressure. There was no difference in terms of the extent of blood pressure reduction between the 2 combination treatment groups. A total of 73 patients who responded to celiprolol monotherapy or one of the combination therapies were treated up to 12 months. The data of 43 patients, who came to all monthly controls, could be evaluated. During the whole period of treatment a constant reduction of elevated blood pressure levels was obtained under treatment with 200 mg celiprolol or in combination with 12,5 mg or 25 mg CT. There was no negative influence on laboratory parameters under celiprolol or combination (12,5 mg CT) therapy. There was a slight increase of uric acid and in 3 cases a decrease of serum potassium under combination therapy with 25 mg CT.

Adrenergic beta-Antagonists↗

[Significance of isolated atrial stimulation as a stress test in comparison with bicycle ergometry].

On 77 patients was performed a comparative examination of load ECG on the bicycle ergometer and isolated atrial stimulation for the diagnosis of an ischaemic heart disease. With 80.5% in the estimation of the two methods with regard to the correct diagnostic classification in relation to the number of patients in the random test a good accordance is the result. With the two methods nearly identical results can be yielded and as to small number of patients with clear indication even an supplementation of the provokation tests performed up to now can be spoken of, since additional diagnostic references to an ischaemic heart disease are possible. But the isolated atrial stimulation cannot supersede the usual load ECG in the diagnostics of the ischaemic heart disease an account of the great methodical expenditure.

Arrhythmias, Cardiac↗

Bilateral virilizing adrenal tumor in a 17 year old woman.

We report on a 17 year old female patient with amenorrhea, hirsutism and slight acne. Hormonal blood analyses showed markedly increased levels for dehydroepiandrosteronesulfate, testosterone and androstenedione. Ultrasound investigation revealed a large tumor above the left kidney and a small area above the right kidney, suspicious for a tumor on the contralateral side. This was confirmed by angiography. During surgery, bilateral tumors were removed. Pathological diagnosis was made as bilateral adenomas of the adrenal cortex. Postoperatively, an impressive normalization was observed, accompanied by a rapid decrease of the elevated hormone concentrations. This case is the first report of a bilateral occurrence of a virilizing tumor of the adrenal cortex.

Adenoma↗

Characterization of a gene product (Sec53p) required for protein assembly in the yeast endoplasmic reticulum.

SEC53, a gene that is required for completion of assembly of proteins in the endoplasmic reticulum in yeast, has been cloned, sequenced, and the product localized by cell fractionation. Complementation of a sec53 mutation is achieved with unique plasmids from genomic or cDNA expression banks. These inserts contain the authentic gene, a cloned copy of which integrates at the sec53 locus. An open reading frame in the insert predicts a 29-kD protein with no significant hydrophobic character. This prediction is confirmed by detection of a 28-kD protein overproduced in cells that carry SEC53 on a multicopy plasmid. To follow Sec53p more directly, a LacZ-SEC53 gene fusion has been constructed which allows the isolation of a hybrid protein for use in production of antibody. With such an antibody, quantitative immune decoration has shown that the sec53-6 mutation decreases the level of Sec53p at 37 degrees C, while levels comparable to wild-type are seen at 24 degrees C. An eightfold overproduction of Sec53p accompanies transformation of cells with a multicopy plasmid containing SEC53. Cell fractionation, performed with conditions that preserve the lumenal content of the endoplasmic reticulum (ER), shows Sec53p highly enriched in the cytosol fraction. We suggest that Sec53p acts indirectly to facilitate assembly in the ER, possibly by interacting with a stable ER component, or by providing a small molecule, other than an oligosaccharide precursor, necessary for the assembly event.

Amino Acid Sequence↗