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Biomedical subjects

A Hoffmann

Publications and source records attributed to A Hoffmann.

At least 217 records · Page 12Linked to original sources
PubMed1995

20 MHz sonography, colorimetry and image analysis in the evaluation of psoriasis vulgaris.

For objective evaluation of the treatment of psoriasis vulgaris standard techniques are desirable. They should be reproducible, sensitive and non-invasive. In this study non-invasive bioengineering techniques, especially high frequency/high resolution ultrasound for measurement of the healing of psoriasis vulgaris were evaluated. Fifty patients with chronic stationary plaque type psoriasis participated in a prospective study; in each patient two psoriatic plaques were examined by means of sonography, colorimetry and image analysis during treatment until complete resolution had occurred. Skin thickness and density could be quantified by means of high frequency ultrasound. In active psoriatic lesions, an echopoor area underneath the entry echo in the ultrasound image caused by acanthosis and inflammatory infiltrate is typical. Under therapy the thickness of this echopoor area diminishes while its density increases. Intensity of the erythema especially the decrease of erythema through healing could not exactly be quantified with the colorimeter because the 'Lab'-CIE-colour representation system cannot distinguish well enough between the colours red and brown. Image analysis allowed to measure the sizes of the psoriatic plaques and to quantify their resolution under therapy. The measuring of plaque size by the aid of computer based image analysis is possible and useful.

Colorimetry↗
PubMed1995

Mouse models of Tay-Sachs and Sandhoff diseases differ in neurologic phenotype and ganglioside metabolism.

Tay-Sachs and Sandhoff diseases are clinically similar neurodegenerative disorders. These two sphingolipidoses are characterized by a heritable absence of beta-hexosaminidase A resulting in defective GM2 ganglioside degradation. Through disruption of the Hexa and Hexb genes in embryonic stem cells, we have established mouse models corresponding to each disease. Unlike the two human disorders, the two mouse models show very different neurologic phenotypes. Although exhibiting biochemical and pathologic features of the disease, the Tay-Sachs model showed no neurological abnormalities. In contrast, the Sandhoff model was severely affected. The phenotypic difference between the two mouse models is the result of differences in the ganglioside degradation pathway between mice and humans.

Animals↗
PubMed1995

[Bronchiectasis and infection incidence in alpha 1-antitrypsin deficiency. The value of high-resolution computed tomography].

UNLABELLED: PURPOSE of this study was to determine the prevalence of bronchiectasis in patients suffering from alpha-1-antitrypsin deficiency and to compare its extent with the frequency of infections. MATERIAL AND METHODS: High-resolution CT examinations (HRCT) of 23 patients with alpha-1-antitrypsin deficiency were retrospectively assessed for extent, severity and localisation of bronchiectasis, bronchial wall thickening and extent of emphysema. Chest radiographs and clinical records were available for correlation. RESULTS: HRCT scans showed bronchiectasis in 14 of 23 patients, bronchial wall thickening in 3/14, and panlobular emphysema in 23/23. Chest radiographs showed bronchiectasis in 4/23 patients. Only two of 9 patients without bronchiectasis had a history of infections; all 8 patients with multiple bronchiectasis had a history of recurrent infections. CONCLUSION: Bronchiectasis is a common finding in alpha-1-antitrypsin deficiency, and is associated with recurrent infections. HRCT is superior to chest radiography as an indicator for the risk of infection in these patients.

Adult↗
PubMed1995

Psychosocial factors predict medical outcome following a first myocardial infarction. Working Group on Cardiac Rehabilitation of the Swiss Society of Cardiology.

BACKGROUND: The aim of this study was to identify psychosocial variables that, in addition to known medical factors, predict the long-term outcome after a first myocardial infarction. PATIENTS AND METHODS: The study population consisted of 222 men aged 30-60 years who entered an inpatient rehabilitation program a mean of 7 weeks after a first myocardial infarction. Medical data and completed questionnaires for psychosocial variables were obtained from the patients and their family physicians at entry to the rehabilitation center and 1 year later. Further data, including answers to a detailed questionnaire, were collected at the beginning of rehabilitation and after one year; this follow-up was 99% complete. RESULTS: The 1-year mortality was 2.2%, the reinfarction rate 1.8%, hospital readmissions for cardiac reasons occurred in 25%, and 13% of the patients underwent a subsequent revascularization procedure. At baseline and after 1 year, respectively, 84 and 83% of the patients were asymptomatic. A poor medical outcome, defined as death, reinfarction, severe symptoms or poor exercise capacity, was seen in 9% of the patients. The most important physiological predictors for an unfavourable medical outcome, found in bivariate and multivariate analyses, were age, severity of infarction, and major coronary risk factors. In addition, some of the psychosocial variables were significantly related to a poor medical outcome: lack of a stable partnership, high work load, poor general well-being with multiple chronic non-specific health complaints, and a low external locus of control (failure to identify disease-promoting factors within own surroundings or lifestyle). CONCLUSIONS: The medical course of coronary artery disease was predicted not only by medical variables but also by psychological and social variables. As well as being addressed directly, these factors may help to identify patients who need to be followed more closely, so that medical complications can be reduced by treating early signs of disease progression more aggressively.

Adult↗
PubMed1995

Pharmacokinetic interactions of nifedipine and quinidine.

Several clinical investigations have been published regarding the interaction of nifedipine and quinidine. The results of these studies are contradictory. In vitro studies indicate that the 3-hydroxylation and N-oxigenation of quinidine appear to involve the P4503A4 family, a form of cytochrome that predominantly catalyzes the aromatization of nifedipine, too. The aim of our study was to investigate the effect of oral intake of 200 mg quinidine on the kinetics of 20 mg nifedipine as a retarded formulation and vice versa. Twelve healthy male volunteers between 18 and 40 years were treated. Each subject was studied on three occasions each separated by a one week washout period. Drug administration consisted of one oral dose of nifedipine (Adalat retard 20 mg), one oral dose of quinidine (Chinidin sulfuricum "Buchler" 200 mg) or a combination of both (20 mg nifedipine and 200 mg quinidine) in a randomised 3 way crossover. Administration of the test drugs in combination slightly increased the bioavailability of both--nifedipine [N] to 18% and quinidine [Q] to 16%--and decreased the clearance of both drugs. The results were not statistically significant. Based on our data, the combination of nifedipine and quinidine seems to lack a clinically relevant interaction.

Adult↗
PubMed1995

Hepatobiliary transport of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors conjugated with bile acids.

To obtain prodrugs with affinity to liver parenchymal cells, the hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors HR 780 and lovastatin (syn. mevinolin) were conjugated with the bile acids cholic acid, taurocholic acid, and glycocholic acid. Hepatic uptake and biliary excretion of the coupled drugs were investigated and compared with the noncoupled drugs. Studies were performed with livers of normal Wistar rats, and TR-/GT- Wistar rats with deficient drug excretion. The experiments showed that the parent drug HR 780 was slowly excreted into bile. In contrast, the excretion of the bile acid-conjugated HR 780 derivatives S 3554 (conjugated with cholate), S 3898 (conjugated with glycocholate), and S 4193 (conjugated with taurocholate) was rapid and very efficient in both groups of rat strains. The bile acid-conjugated HMG-CoA reductase inhibitors showed a 10 to 20 times higher affinity for the uptake systems of bile acids than the noncoupled parent drug compounds, and even higher affinities than the bile acids themselves. The cholate conjugate of HR 780 (compound S 3554) was shown to be a noncompetitive inhibitor of taurocholate uptake and a competitive inhibitor of sodium-independent cholate uptake (Ki = 1 mumol/L). Uptake of radiolabeled S 3554 into isolated rat hepatocytes was observed to be rapid, cell specific, saturable, energy dependent, and carrier mediated. However, the carrier for S 3554 uptake was found not to be the cloned Na(+)-dependent taurocholate cotransporting polypeptide Ntcp. Expression of this carrier cRNA in Xenopus laevis oocytes did not stimulate S 3554 uptake.

ATP-Binding Cassette Transporters↗
PubMed1995

Dipyrone and diclofenac do not influence creatinine-clearance, inulin-clearance or PAH-clearance in healthy male volunteers.

The effects of the non-steroidal anti-inflammatory drug diclofenac and the pyrazolone derivative dipyrone on renal function were compared with those of placebo in 12 healthy male volunteers in a randomized, controlled, triple-crossover study with a wash-out period of 4 days between each of the 3 trial periods (dipyrone, diclofenac and placebo) which lasted three days each. The volunteers received dipyrone (1 g, 3 times/day for 2 days, followed by twice 1 g on the main trial day, which was day 3 of each study period) or diclofenac (50 mg, 3 times/day for 2 days, followed by twice 50 mg on the main trial day) or placebo orally. Standardized meals (50 mEq sodium per day) were given from one week before the start until the end of the study and on the main trial days a protein-rich lunch (2 g protein/kg body weight) was taken. Renal function was assessed in each study period by measurement of creatinine-clearance, inulin-clearance and p-aminohippurate (PAH)-clearance to characterize glomerular filtration rate and renal plasma flow. High protein intake induced glomerular hyperfiltration (increased creatinine-clearance, inulin-clearance and PAH-clearance) in all 3 study periods (dipyrone, diclofenac, placebo). Dipyrone and diclofenac had no effect on renal clearance of creatinine, inulin or PAH in comparison to placebo. These results show that dipyrone and diclofenac at therapeutic dosages over 3 days do not decrease glomerular filtration and renal plasma flow in healthy individuals. Furthermore, it is unlikely that prostaglandins play a major role in protein-induced glomerular hyperfiltration.

Administration, Oral↗
PubMed1995

[A 63-year-old man with uncorrected tetralogy of Fallot].

An exceptional case of tetralogy of Fallot is reported; the patient survived without severe symptoms or surgical treatment. The diagnosis was made by echocardiography at the age of 61 years when the patient experienced hypertensive retinopathy. Death occurred at 63 from myocardial infarction. It is thought that longstanding hypertension had contributed to a diminished right-to-left shunting, thus reducing cyanosis and hypoxic damage to the myocardium, which enabled prolonged survival.

Coronary Vessels↗
PubMed1995

Study on the bioequivalence of an oral nifedipine formulation and a sustained release reference preparation after single dose and repeated doses.

Pharmacokinetic parameters of an oral formulation of nifedipine (CAS 21829-25-4, Corinfar, test preparation T a dragee with 10 mg nifedipine) were compared with a reference preparation (R, a sustained release tablet with 20 mg nifedipine) in 16 healthy volunteers in a open two-way crossover study under the influence of ingestion of food. A GC/MS method was used to analyse the serum samples. The estimation of bioequivalence was based on a nonparametric statistical procedure of analysis of variance. Both, the test preparation T and the reference preparation R are bioequivalent at steady state. The main pharmacokinetic parameters (mean +/- standard deviation) used for the bioequivalence decision at steady state were AUC0- tau ss (T: 351.4 +/- 161.0 ng.ml-1.h; R: 345.5 +/- 146.8 ng.ml-1.h), Cmaxss (T: 67.3 +/- 29.5 ng.ml-1; 66.9 +/- 33.0 ng.ml-1) and HVDss (T: 3.8 +/- 1.3 h; R: 4.2 +/- 1.8 h). The bioequivalence of rate and extent of absorption was proved for both preparations at steady state by assessing mean serum level curves as well as by statistics (90% confidence intervals) using the main pharmacokinetic parameters AUC0 - tau ss (range: 0.84-1.02 point estimator: 0.92), Cmaxss (0.95-1.33; 1.15) HVDss (0.72-0.98; 0.82). The large interindividual variability of pharmacokinetics is typical of the drug and does not depend on the formulation used. No case of severe disturbance of circulatory function or other adverse events with the duty to treat occurred during the study. No volunteer dropped out.

Administration, Oral↗
PubMed1995

Analysis of amount, expenditures and indications of drug and blood product prescriptions at surgical intensive care units.

Analysis of indication-related drug prescription patterns is of particular interest with regard to rising costs of the health service being also reflected in higher expenditures for drugs at the University Hospital of the Friedrich-Schiller-University Jena. This is especially important at ICU's, since treatments in patients with acute or chronic multiorgan failure are very expensive. Over a period of 4 months in 1994 the indication-related drug consumption of 2 surgical ICU's of the University of Jena has been recorded and analyzed using a notebook-PC. The total costs of these drugs and blood products, which caused 80% of total costs in the last year, came up to 1,144,773 DM for 465 patients. Nearly two thirds of the recorded expenditures were caused in patients with severe trauma or with acute bleeding. The 10 leading substances (antithrombin III, human albumin 20%, prothrombine complex, etc.) represent 67% of total costs including blood products, antibiotics/antimycotics and IgM enriched intravenous immunoglobulines. Therefore, the indications of these drugs in particular have been further investigated. During and after the study the results have been discussed with the treating medical staff leading to new therapy recommendations. Until the end of 1994 a remarkable cost saving could already be achieved for some drugs by more critical and purposeful use providing same high standard of medical treatment. Blood products have to be included into analyses of indication-related drug administration on the meaning of high costs, difficulties of accurate indication, and possibly undesired side-effects. However, medical and ethical aspects, e.g. minimizing of side-effects, have to take priority over pharmacoeconomical considerations especially in intensive care medicine.

Animals↗
PubMed1994

Bile acid derived HMG-CoA reductase inhibitors.

The target organ for HMG-CoA reductase inhibitors to decrease cholesterol biosynthesis in hypercholesterolemic patients is the liver. Since bile acids undergo an enterohepatic circulation showing a strict organotropism for the liver and the small intestine, the structural elements of an inhibitor for HMG-CoA reductase were combined with those for specific molecular recognition of a bile acid molecule for selective uptake by hepatocytes. Either, the HMG-CoA reductase inhibitors HR 780 and mevinolin were covalently attached to 3 xi-(omega-aminoalkoxy)-7 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oic acids to obtain bile acid prodrugs, or the side chain of bile acids at C-17 was replaced by 3,5-dihydroxy-heptanoic acid--a structural element essential for inhibition of HMG-CoA reductase--to obtain hybrid bile acid: HMG-CoA reductase inhibitors. The prodrugs could, as expected, not inhibit rat liver HMG-CoA reductase to a significant extent, whereas the hybrid inhibitors showed a stereospecific inhibition of HMG-CoA reductase from rat liver microsomes with an IC50-value of 0.7 microM for the most potent compound S 2467 and 6 microM for its diastereomere S 2468. Uptake measurements with isolated rat hepatocytes and ileal brush-border membrane vesicles from rabbit small intestine revealed a specific interaction of both classes of bile acid-derived HMG-CoA reductase inhibitors with the hepatocyte and ileocyte bile acid uptake systems. Photoaffinity labeling studies using 3-azi- or 7-azi-derivatives of taurocholate with freshly isolated rat hepatocytes or rabbit ileal brush-border membrane vesicles revealed a specific interaction of bile acid derived HMG-CoA reductase inhibitors with the respective putative bile acid transporters in the liver and the ileum demonstrating the bile acid character of these derivatives, both for the prodrugs and the hybrids. Cholesterol biosynthesis in Hep G2 cells was inhibited by the bile acid prodrugs with IC50-values in the range of 68 nM to 600 nM compared to 13 nM for HR 780 and 130 nM for mevinolin. Among the hybrid inhibitors, S 2467 was the most active compound with an IC50-value of 16 microM compared to 55 microM for its diastereomere S 2468. Preliminary in vivo experiments showed an inhibition of hepatic cholesterol biosynthesis after oral dosage only with prodrugs such as S 3554, whereas the hybrid molecules were inactive after oral application.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Synthesis and biological activity of bile acid-derived HMG-CoA reductase inhibitors. The role of 21-methyl in recognition of HMG-CoA reductase and the ileal bile acid transport system.

To increase hepatoselectivity of HMG-CoA reductase inhibitors by using the specific bile acid transport systems, deoxycholic acid-derived inhibitors 9 and 11 have been synthesized, on the basis of the concept of combining in one molecule structural requirements for specific inhibition of the HMG-CoA reductase and specific recognition by the ileal bile acid transport system. The 1-methyl-3-carboxylpropyl subunit of deoxycholic acid was replaced by the 3,5-dihydroxyheptanoic acid lactone of lovastatin, and position 12-OH was esterified with 2-methylbutyric acid. Compounds 9 and 11 were evaluated for their inhibitory activity on rat liver HMG-CoA reductase, cholesterol biosynthesis in HEP G2 cells, and [3H]taurocholate uptake in rabbit brush border membrane vesicles and compared with methyl derivatives 8 and 10. The steroidal 21-CH3 group affects both activity on HMG-CoA reductase and recognition by the ileal bile acid transport system.

Androstanols↗
PubMed1994

Photoactive mitochondria: in vivo transfer of a light-driven proton pump into the inner mitochondrial membrane of Schizosaccharomyces pombe.

The light-driven proton pump bacteriorhodopsin (bR) from Halobacterium salinarium has been genetically transferred into the inner mitochondrial membrane (IM) of the eukaryotic cell Schizosaccharomyces pombe, where the archaebacterial proton pump replaces or increases the proton gradient usually formed by the respiratory chain. For targeting and integration, as well as for the correct orientation of bR in the IM, the bacterioopsin gene (bop) was fused to signal sequences of IM proteins. Northern and Western blot analysis proved that all hybrid gene constructs containing the bop gene and a mitochondrial signal sequence were expressed and processed to mature bR. Fast transient absorption spectroscopy showed photocycle activity of bR integrated in the IM by formation of the M intermediate. Experiments with the pH-sensitive fluorescence dye 2',7'-bis(2-carboxyethyl)-5 (and -6)-carboxyfluorescein revealed bR-mediated proton pumping from the mitochondrial matrix into the intermembrane space. Glucose uptake measurements under anaerobic conditions showed that yeast cells containing photoactive mitochondria need less sugar under illumination. In summary, our experiments demonstrate the functional genetic transfer of a light energy converter to a naturally nonphotoactive eukaryotic organism.

Bacteriorhodopsins↗
PubMed1994

Grapefruit juice inhibits 7-hydroxylation of coumarin in healthy volunteers.

The effect of grapefruit juice on the urinary excretion of 7-hydroxycoumarin after oral administration of 10 mg coumarin, as an index of cytochrome P450 dependent coumarin metabolism, has been investigated in an open, randomised cross over study in 13 healthy volunteers (7 female, 6 male). The percentage of 7-hydroxycoumarin found in urine was significantly decreased up to 8 h after simultaneous intake of 300 ml grapefruit juice. If the same volume of juice was swallowed 30 min prior to the administration of coumarin, 7-hydroxycoumarin excretion was delayed by up to 6 h. MRTexcr. of coumarin was 70% extended by coadministration of grapefruit juice. It appears that grapefruit flavonoids inhibit cytochrome P450 2A dependent metabolic pathways. The mechanism of cytochrome P450 inhibition by these flavonoids is still poorly understood.

Adult↗
PubMed1994

Involvement of the cholinergic system and the basal midbrain in the organization of tonic immobility in the toad Bufo paracnemis.

Microinjection of 200 ng carbachol into the midbrain tegmentum of awake toads increases the duration of tonic immobility episodes induced by postural inversion maneuvers and by movement restriction. These increases were statistically significant when compared to those induced in untreated animals and in animals microinjected with an equivalent volume (0.2 microliter) of saline at the same site, and were partially blocked by pretreatment with atropine. The potentiation of tonic immobility episodes was not due to cardiovascular, respiratory, or motor changes caused by carbachol microinjection because these changes had a mean duration of 30 min and the immobility episodes induced both before and after carbachol injection did not present predictable durations but lasted either less or more than 30 min.

Animals↗