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Biomedical subjects

A Hoffmann

Publications and source records attributed to A Hoffmann.

At least 181 records · Page 10Linked to original sources
PubMed1997

Nilvadipine in hypertension--experience in ambulatory treatment.

To investigate the 24-hour efficacy of nilvadipine (8 and 16 mg)in patients with mild to moderate essential hypertension, a double-blind, randomized, placebo-controlled, multicenter study with 3 parallel medication groups (placebo, 8, and 16 mg nilvadipine) was performed. Included in the study were 172 outpatients of both sexes with a mean age of 56 years. The primary target variable for the evaluation of efficacy was the difference in sitting diastolic blood pressure 24 hours after administration of the trial medication, in mmHg, achieved by the different doses after 8 weeks of therapy compared to baseline. This difference was -6.8 in the placebo group (n = 59), -10.4 in the nilvadipine 8 mg group (n = 60), and -11.0 in the nilvadipine 16 mg group (n = 49). Paired comparison showed a significant and clinically relevant difference between placebo and both nilvadipine doses. There were no serious adverse events reported. Nonserious adverse events were reported in 40.1% of all patients. Most frequently reported adverse drug reactions were flushing, headache, edema, and tachycardia. The adverse events occurred dose-dependently. As the dose-response relationship shows clinical saturation at a daily dose of 16 mg, the recommended dose is 8 mg taken once daily.

Adolescent↗
PubMed1997

A single and multiple dose bioavailability study with carbamazepine 400 mg retard tablets with reference to enzyme autoinduction and circadian time differences.

UNLABELLED: Both single and multiple dose bioequivalence studies are required to assess the quality of modified release formulations of drugs. In bioequivalence studies of drugs with enzyme autoinducing properties such as carbamazepine (CBZ), the standard multiple dose study design must be modified to guarantee equivalence of drug elimination. This problem was considered with regard to carbamazepine 400 retard AWD (test) whose bioavailability relative to a listed reference (Tegretal 400 retard) was studied in 2 randomized, open, crossover studies both with 18 healthy volunteers of Caucasian origin (20-36 years, 61.5-92 kg, 172-195 cm). The single dose study was done with 400 mg CBZ. Serum concentration time profiles of CBZ and its active metabolite CBZ-10,11-epoxide were determined until 144 h after administration. The multiple dose study was performed with 400 mg CBZ b.i.d. for 15 days (first 2 days: 200 mg b.i.d.) followed by a 7-day study with the alternative investigational product. 24-hour serum concentration time profiles of CBZ and its metabolite were measured on days 15 and 22 of the study. The quantitative drug analysis was done with an HPLC method the quality of which fulfilled the requirements of bioequivalence studies. Test was considered bioequivalent to reference with regard to the extent of absorption, if the 90% confidence intervals of the AUC0-infinity ratio (single dose) and AUC0-24h ratio (multiple dose) were within the range of 0.80-1.25, and with regard to rate of absorption if the 90% confidence intervals of the Cmax/AUC ratio (single dose) or AUCF0-24h ratio were within 0.70-1.43. The point estimators (90% confidence limits) of the AUC ratio (test/reference) of CBZ were 0.979 (0.94, 1.02) for the single and 1.01 (0.947, 1.076) for the multiple dose comparison. The point estimator (90% confidence limits) of the Cmax/AUC ratio was 0.989 (0.959, 1.020) and of the AUCF0-24h ratio 1.066 (0.937, 1.212). There were no circadian time differences in any pharmacokinetic parameter. IN CONCLUSION: Carbamazepine 400 retard AWD tablets were bioequivalent to reference with regard to extent and rate of absorption after both single and multiple dose administration.

Adult↗
PubMed1997

[Concealed perforated aneurysm of an aberrant right hepatic artery: papillary bleeding. Case report and review of the literature].

A rare case of spurious aneurysm of an aberrant right hepatic artery is reported. Endoscopic retrograde cholangio-pancreaticography, computed tomography and selective angiography of the coeliac trunc are diagnostic. Resection of the aneurysm and interposition of saphenous vein is the preferred procedure. In selected cases ligation of the common hepatic artery is possible. Intrahepatic aneurysms are preferably treated interventionally.

Aged↗
PubMed1997

The role of respiratory muscles in the impairment of the respiratory system function in the workers of a chemical plant division producing pesticides.

Workers of a chemical plant department producing dust and liquid pesticides (37 males and 17 females) exposed to dust containing free silica, organic solvents and active substances, among others: organophosphate compounds, pyrethroids, triazines, carbamates and dithiocarbamates, 2,4-D, captan, carboxine, carbendazim and dodine were studied. Spirometric investigations, including evaluation of vital capacity (VC), 1 second forced expiratory volume (FEV1) and its percentage index (FEV1%VC), peak expiratory flow and maximal end-expiratory flow (MEF25), were performed directly at the workplace. At the same time mouth inspiratory pressures (MIP) and maximal expiratory pressures (MEP) were evaluated. Chronic bronchitis (according to BMRC questionnaire) was diagnosed in every second worker, and in 11 males and females obstructive impairment of pulmonary function was established; 41% of females and 27% of males were found to have diminished peak expiratory flow. Maximal inspiratory pressures were significantly lower both in the studies males (p < 0.001) and females (p < 0.02) than those in the control groups and amounted to 74.4 +/- 21.5 and 58.1 +/- 24.3 cm H2O, respectively. Maximal expiratory pressures were also significantly lower in the studied males (p < 0.001) and females (p < 0.05) and amounted to 116.6 +/- 28.4 and 74.5 +/- 17.9 cm H2O, respectively. Significant correlation between decreased PEF and the force of expiratory muscles-MEP (In males r = 0.3279, p < 0.05; In females r = 0.7049, p < 0.01) was founded. The investigations performed at the workplace allow the assumption that work at the production of pesticides may result in impairment of pulmonary ventilation, development of chronic bronchitis as well as impaired function of respiratory muscles.

Adult↗
PubMed1997

[Early post myocardial infarction syndrome--a trial of assessment based on clinical course and immunologic tests].

The study analysed clinical and immunological course of 22 patients (aged 56.3 +/- 9.5) with fever (38.5 degrees C) and greatly increased erythrocyte sedimentation rate (ESR) in the first week after myocardial infarction. The control group consisted of 25 patients (aged 50.7 +/- 11.2) without inflammatory and infectious diseases. Clinical courses of the disease, chest x-ray, echocardiography, leucocytosis and serial CK-MB levels were analysed. The immunological investigations involved quantitative estimation of IgG, C3 complement, C4 complement and the identification of T and B lymphocytes on the basis of the rosette tests A, E and EAC. Post myocardial infarction syndrome (PMIS) manifested by fever and greatly increased ESR we observed in 64% of examined patients, but fully manifested PMIS in 14% with tendency to recurrences. We found the differences in immunological examinations compared to the control group. Pericardial effusion occurred in 64% of the patients. The treatment with corticosteroids brought dramatic relief of the symptoms with objective improvement of clinical condition. Patients with high temperature with accompanying greatly raised ESR in the first week after MI may demonstrate abortive form of the post myocardial infarction syndrome.

Aged↗
PubMed1996

Mitotic regulation of TFIID: inhibition of activator-dependent transcription and changes in subcellular localization.

Mitosis in higher eukaryotes is accompanied by a general inhibition of transcription. To begin to understand the mechanisms underlying this inhibition we have examined the behavior of the general transcription factor TFIID during mitosis. Immunocytochemistry and subcellular fractionation studies indicate that the majority of TFIID is displaced from the disassembling prophase nucleus to the mitotic cytoplasm around the time of nuclear envelope breakdown. However, a subpopulation of TFIID remains associated tightly with the condensed mitotic chromosomes. Metabolic labeling of mitotic cells revealed that several subunits of TFIID undergo mitosis-specific phosphorylation, but in spite of these changes, the TFIID complex remains intact. Functional analysis of purified TFIID from mitotic cells shows that phosphorylated forms are unable to direct activator-dependent transcription, but that this activity is restored upon dephosphorylation. These results demonstrate that TFIID regulation by phosphorylation is likely to have an important role in mitotic inhibition of RNA polymerase II transcription. In addition, they suggest a mechanism for regulating gene expression through the selective disruption of polymerase II promoter structures during mitosis.

Cell Fractionation↗
PubMed1996

[Cardiac risk assessment for athletic training].

Regular physical activity has unequivocal health benefits: however, cardiac complications and sudden death do occur during physical activity, particularly in unfit persons. In younger individuals these are predominantly due to congenital anomalies of the conduction system or the coronary arteries and to left ventricular outflow tract obstruction (aortic stenosis, hypertrophic cardiomyopathy). In persons above the age of 40 the predominant cause is coronary artery disease. A further common cause in all age groups seems to be a silent myocarditis occurring during an otherwise uncomplicated viral illness; therefore, the physician is confronted with the difficult task to generally advise increased physical activity but to recognize individuals at increased risk for cardiac complications. A careful history is of key importance in the assessment of the aptitude for physical training. It may reveal a history or current symptoms of heart disease as well as individual and familial risk factors. Physical examination may show abnormal findings on palpation, auscultation or exercise testing. In selected cases, an echocardiogram or another, more thorough investigation is indicated. An individual risk assessment and recommendations for physical activity even for persons at increased risk can be derived from these methods.

Adolescent↗
PubMed1996

Cloning and characterization of human TAF20/15. Multiple interactions suggest a central role in TFIID complex formation.

TFIID is a multiprotein complex that plays a central role in the initiation and regulation of class II transcription. Transcription factor IID (TFIID) nucleates transcription initiation complex formation by direct core promoter binding and mediates the action of transcriptional activators, in part via direct interactions with them. Molecular studies of the TFIID complex have identified multiple subunits whose potential interactions can be recapitulated in vitro with recombinant polypeptides. Here we report the cloning of human TATA box binding protein (TBP)-associated factor 20 (TAF20) and the consequent identification of an additional, related TFIID subunit, human TAF15 (hTAF15). Multiple TAF20/15 interactions have been detected within native TFIID preparations and further analyzed with recombinant subunits. Along with the demonstration of a high affinity association between TAF20/15 and TBP, the present results suggest that hTAF20/15 may complement hTAF250 in directing the association of TAFs with TBP to form a TFIID complex. Finally, we present detailed mutagenesis studies that reveal multiple, distinct interaction surfaces on the presumed globular domain of hTAF20/15 and may be used, in conjunction with structural data, to model the architecture of the TFIID multiprotein complex.

Amino Acid Sequence↗
PubMed1996

Structural similarity between TAFs and the heterotetrameric core of the histone octamer.

A complex of two TFIID TATA box-binding protein-associated factors (TA FIIs) is described at 2.0A resolution. The amino-terminal portions of dTAFII42 and dTAFII62 from Drosophila adopt the canonical histone fold, consisting of two short alpha-helices flanking a long central alpha-helix. Like histones H3 and H4, dTAFII42 and dTAFII62 form an intimate heterodimer by extensive hydrophobic contacts between the paired molecules. In solution and in the crystalline state, the dTAFII42/dTAFII62 complex exists as a heterotetramer, resembling the (H3/H4)2 heterotetrameric core of the histone octamer, suggesting that TFIID contains a histone octamer-like substructure.

Amino Acid Sequence↗
PubMed1996

A histone octamer-like structure within TFIID.

The general transcription factor TFIID nucleates initiation complex formation through direct core promoter binding, commits promoters within chromatin to transcription, and mediates the action of transcriptional activators, a phenomenon that may correlate with enhanced TFIID recruitment or conformational changes in TFIID-promoter complexes. Molecular studies of the multiprotein TFIID complex have identified a primary TATA binding subunit (TBP), TBP-associated factors (TAFs) that interact with and mediate the function of activators and intersubunit interactions but have yielded relatively little insight into the structural organization of the complex or the actual mechanism of transcriptional activation. Here we present biochemical evidence for the structural relevance of histone homologies in the human TFIID subunits hTAF80, hTAF31 and hTAF20/15. Together with analyses of native TFIID complexes and accompanying crystallographic studies, the results suggest that there is a histone octamer-like TAF complex within TFIID.

Amino Acid Sequence↗