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Biomedical subjects

H Hoffmann

Publications and source records attributed to H Hoffmann.

At least 127 records · Page 7Linked to original sources
PubMed1992

[2-Amino-oxazoles as potential H-bonding agents in virostatic research. 4. Pharmacokinetics and pharmacologic-toxicologic profile of 2-guanidino-4,5-dipropyloxazole hydrochloride].

Out of the group of 2-amino-oxazoles 1 was found to be the most potent antiviral compound. Following p.o. or s.c. administration to rats, the 14C-labeled 1 was quickly and completely absorbed. The TRA was eliminated mainly via the kidneys and the liver with half-lives between 32 and 42 h. The acute pharmacodynamic effects of 1 were decrease of blood pressure, bradycardia, and inhibition of both gastric emptying and acid secretion. On smooth muscles spasmolytic and alpha-anti-adrenergic actions were predominant. After single administration the following MTD's were determined: 30 (mouse), 20 (rat), 10 mg/kg i.v. (pig), and 500 (mouse, rat), greater than 100 mg/kg p.o. (pig), respectively. In a subchronic toxicity study in rats, oral doses of 1 between 15 and 240 mg/kg given daily for 4 weeks were tolerated without any severe alterations related to the drug.

Administration, Oral↗
PubMed1992

Influence of leukemia P388 on plasma concentration-time profiles of bendamustine in B6D2F1 mice.

It was the aim of this study to investigate whether leukemia P388 being an important murine transplantation tumor may alter the plasma concentration-time profiles of the alkylating antineoplastic agent bendamustine (1) in mice. In an advanced tumor stage the rapid decline of 1 plasma levels was found to be retarded in tumor-bearing in comparison to tumor-free animals both after i.v. and p.o. drug administration. These changes cannot be explained by the neoplasia-related depression of drug metabolism whereas the 1-containing ascitic fluid may be a possible reason for the prolonged drug levels in plasma. After p.o. administration of 1, the bioavailability of the drug was found to be increased in the leukemia-bearing animals.

Administration, Oral↗
PubMed1992

[PASS: a community, system-related program for occupational rehabilitation of chronic psychiatric patients in competitive employment].

Notwithstanding considerable success, the concepts currently applied by vocational rehabilitation workshops for persons with chronic mental illness are deemed open to criticism in some respects. Presented is the PASS programme, developed on the basis of more than two decades of experience with the clinic's own rehabilitation workshop. The greater part of the five-phase programme no longer occurs within the workshop but is spent at training workplaces with regional firms. A mobile rehabilitation team does not only support the patients at their training facilities but also their colleagues and immediate superiors, who have been prepared for their forthcoming tasks by psychoeducational information meetings. These community-based, ecological system-related aspects of the programme are complemented by repetitive social skills training and group work with relatives. Assessments carried out in each phase provide important decision-making data for programme development and render its scientific evaluation possible. Our experience so far demonstrates the possibility of recruiting enterprises to provide training places.

Activities of Daily Living↗
PubMed1991

A purified antithrombin III--heparin complex as a potent inhibitor of thrombin in porcine endotoxin shock.

Inhibition of activated clotting factors is an important therapeutic approach in disseminated intravascular coagulation (DIC). We examined the possible protective effect of a purified complex of human antithrombin III (AT III) and heparin in endotoxin-induced DIC in pigs. Two groups of endotoxemic pigs were studied. AT III-heparin group pigs (n = 8) were pretreated with a bolus injection of 500 units AT III-heparin complex, followed by a continuous infusion of 1000 units of the complex for 6 hours given simultaneously with the infusion of 10 micrograms/kgh of S. abortus equi endotoxin. Controls (n = 9) were given saline in addition to the continuous infusion of endotoxin. AT III activity, prothrombin and soluble fibrin in plasma were determined by chromogenic substrate methods. Fibrinogen was measured turbidimetrically. Human AT III antigen in the treated group was 64 +/- 3% at 2 hours and increased to 84 +/- 4% until the end of the experiment. AT III activity in the AT III-heparin group was elevated throughout the whole observation period (greater than 100%), whereas it was significantly lower in the controls. Prothrombin decreased similarly in both groups by approximately 35% until the end of the experiment. AT III-heparin treatment significantly attenuated the endotoxin-induced consumption of fibrinogen and completely prevented the increase in soluble fibrin in plasma. However, no significant effect of AT III-heparin was observed on endotoxin-induced mortality and dysfunction in pulmonary gas exchange. Therefore we conclude that the purified AT III-heparin complex inhibits thrombin effects and prevents development of DIC, but fails to significantly influence clinical outcome in endotoxin shock of the pig.

Animals↗
PubMed1991

Establishing intermodal equivalence in preweanling and adult rats.

Interactions between olfactory and brightness conditioning were examined in infant (16-day-old) and adult rats. Conditioning to an odor (methyl salicylate [MS] paired with footshock [FS]) was followed by subthreshold conditioning to an unscented black box (paired with FS). Controls were given unpaired presentations in either the 1st or the 2nd phase of this treatment. No age-related differences in conditioning occurred when either phase was presented alone. Significant aversion to the black box was observed after the experimental treatment only in infants, and brightness conditioning potentiated odor conditioning in infants but not adults. In the infants, odor-extinction procedures weakened the aversion to the black box as well as to MS. Olfactory-to-visual transfer required that the same unconditioned stimulus be paired with both conditioned stimuli. These results may reflect an infantile disposition for unitization.

Aging↗
PubMed1991

[Clinical significance and fetal outcome in end-diastolic decreased flow in the umbilical artery and/or fetal aorta: analysis of 51 cases].

The AEDV in the umbilical artery or the foetal aorta is considered to be the most severe waveform abnormality. Using pulsed Doppler, we found such a waveform in 51 foetuses out of 954 high-risk pregnancies (33/51 in both vessels, 17/51 aorta only and 1/51 umbilical artery only). A reverse flow was registered in 24 foetuses. The outcome was compared with that of a control group (n = 72) showing normal Doppler findings. The following parameters were highly significant (p less than 0.001): Rate of Caesarean section owing to foetal distress (85.3% to 4.8%), of growth retardation (IUGR) (66.7% to 6.0%), of premature delivery (73.5% to 7.5%), of low postnatal pH- and Apgar score (73.5 to 12.1%), of admission to the neonatal intensive care unit (94.1% to 8.6%), of morbidity (35.3% to 2.3%) and of mortality (41.1% to 0%). We observed 17/51 intrauterine and 4/51 postnatal deaths. The rate of malformations was 35.3% with 4 cases of aneuploidy. Considering the malformations, the rate of corrected mortality was 23%. We found, that the association of an AEDV and the absence of severe IUGR is highly suspicious of malformation. We also observed, that congenital heart diseases (CHD) could lead to an AEDV too. An AEDV precedes a pathological cardiotocogram (CTG) with a latency of 0 to 35 days (mean 9.5 days). This latency is not predictable, but we think, that a reliable assessment of jeopardy is possible by analysing further vessels (Aa. arcuatae, A. renalis, A. carotis interna): 72.5% of the foetuses with AEDV had high indices in the carotid artery and 93.1% among these showed a pathological CTG pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta↗
PubMed1991

Time dependent release of tissue-type plasminogen activator and plasminogen activator inhibitor into the circulation of pigs during shock.

To investigate short-term activation and inhibition of fibrinolysis during shock, we studied plasma levels of tissue-type plasminogen activator (t-PA) and t-PA inhibition capacity (PAI) in anaesthetized pigs. t-PA in euglobulin fractions of plasma was measured by the conversion of plasminogen to plasmin in the presence of fibrin split products. Plasmin thus generated was measured in a chromogenic substrate assay. PAI was measured as plasma inhibition capacity for human melanoma t-PA. Controls (n = 8) had constant t-PA and PAI for 6 h. Lipopolysaccharide from Salmonella abortus equi in four different doses (n = 9 - 11), or live Escherichia coli (n = 3) induced a transient t-PA increase with peak values at 2 h. PAI decreased to 50% at 2 h and increased to 250% at 6 h. Phorbol myristate acetate (n = 7) induced no change of t-PA or PAI. Dextran sulphate (n = 4) produced a t-PA rise at 30 min, followed by a rapid decline. Endotoxin was an appropriate stimulus for activation and inhibition of fibrinolysis whereas phorbol ester failed to elicit this response.

Animals↗
PubMed1991

Pentoxifylline does not attenuate acute lung injury in the absence of granulocytes.

Pentoxifylline (PTX), a methylxanthine, can suppress polymorphonuclear leukocyte (PMN) activation and attenuate sepsis-induced acute lung injury. We investigated whether PTX prevents non-PMN-dependent lung injury. First we studied four groups of granulocyte-depleted guinea pigs (control, PTX, Escherichia coli, and E. coli + PTX). Lung injury was assessed by wet-to-dry lung weight (W/D) ratio and lung tissue-to-plasma 125I-albumin ratio (albumin index, AI). The E. coli group showed a significant increase in the lung W/D ratio and AI compared with the control and PTX groups. However, PTX did not prevent the E. coli-induced increase in the lung W/D ratio and AI. Next we investigated the effects of PTX on endothelial cell monolayer permeability and adenosine 3',5'-cyclic monophosphate (cAMP) levels. Whereas E. coli lipopolysaccharide (LPS) alone increased the endothelial permeability, PMNs added to the endothelial monolayers and exposed to LPS enhanced the increase. PTX attenuated the permeability increase mediated by LPS-exposed PMNs. PTX did not prevent the LPS-induced increase in permeability when PMNs were not present, although PTX increased endothelial cell cAMP levels. These data demonstrate that 1) PTX does not prevent lung injury in granulocyte-depleted guinea pigs; 2) PTX does not prevent LPS-induced increases in endothelial cell permeability, despite increased cAMP levels; and 3) PTX attenuates PMN-dependent increases in endothelial cell permeability.

Animals↗
PubMed1991

Early post-treatment with pentoxifylline or dibutyryl cAMP attenuates Escherichia coli-induced acute lung injury in guinea pigs.

We examined effects of early post-treatment with the methylxanthine pentoxifylline (PTXF), or the cell-permeable adenosine 3', 5'-cyclic monophosphate (cAMP) analog dibutyryl cAMP (db-cAMP) on Escherichia-coli-induced acute lung injury in guinea pigs. Acute lung injury was assessed by measurements of lung water (lung wet/dry weight ratio; W/D ratio), the concentration ratio of 125I-albumin in bronchoalveolar lavage (BAL) fluid and lung tissue compared with plasma (albumin index; BAL-AI or tissue-AI), and total differential leukocyte count in BAL fluid. Mean arterial pressure (Pa) and peripheral WBC counts were monitored continuously over the 8-h experiment. Septicemia was induced by a bolus injection of 2 x 10(9)/kg live E. coli. Thirty minutes later the animals received a bolus injection followed by continuous infusion of PTXF (20 mg/kg + 20 mg/kg/h; n = 8) or db-cAMP (2 mg/kg + 2 mg/kg/h; n = 8) or saline (septic control; n = 8). Nonseptic control groups were also studied. The lung W/D ratio, BAL-AI, lung tissue-AI, and BAL leukocyte count increased significantly in the septic control group. The PTXF-septic and db-cAMP-septic groups showed no significant increase in lung W/D ratio, BAL-AI, and lung tissue-AI. However, there was no difference in BAL total and differential leukocyte count as compared with the septic control group. PTXF and db-cAMP had no effect on E. coli-induced changes in peripheral WBC count and Pa. Comparison in vitro experiments demonstrated that PTXF and db-cAMP inhibited the endotoxin-induced (E. coli) chemiluminescent response of isolated guinea-pig polymorphonuclear leukocytes (PMN).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

[Fetal echocardiography. II. Normal and pathological anatomy in real-time ultrasonography].

The paper is a practical approach to fetal echocardiography using real-time ultrasound. The normal sonoanatomy of the fetal heart is presented for the non-cardiologist. The basic cross-sectional views are explained as well as the systematic analysis of the different fetal heart structures. The main heart malformations are reviewed with a description of their appearance in prenatal real-time-ultrasound illustrated by some figures. The examination of the fetal heart could be easy learned, but the assessment and the differentiation of congenital heart defects are only possible by a systematic approach, experience and patience. The examination of the fetal heart should be therefore involved in the screening-ultrasound performed by the prenatal sonographer and suspicious findings has to be referred to a perinatal center.

Echocardiography↗
PubMed1991

[The function of the round table in social psychiatric ambulatory care].

The round table is the center of the activities in the outpatient service of the Sociopsychiatric University Clinic Bern. First the life at the round table is shortly described. Then the different functions of the round table in the care of psychiatric longterm patients are discussed in detail. So the patients, who are partly considerably handicapped, out of their social isolation. The so arising relationships can be helpful for the patients in different areas. Furthermore it can be shown, that the round table fullfills all the functions of an informal, open, sociotherapeutic group. We emphasize on the great importance of the open and tolerant atmosphere at the round table for the therapeutic effect of it.

Activities of Daily Living↗
PubMed1991

[What does 31 phosphorus magnetic resonance spectroscopy measure?A validation in healthy probands].

With 31P nuclear magnetic resonance spectroscopy skeletal muscle metabolism can be measured noninvasively. Aim of this study was to investigate intraindividual reproducebility, interindividual variability, and the correlation of the NMR parameters PCr, alpha-, beta-, gamma-ATP to graded exercise. Reproducebility and variability of PCr values were comparabel to changes of the pH value. Alpha-, beta-, gamma-ATP did not change during measurements. Correlations between the workload and the changes of the NMR parameters were rare. It was found that the intraindividual reproducebility is low and the interindividual variability is high. No systematic correlation between the NMR parameters and the workload could be seen. The termination of exercise in healthy volunteers is not explained by energy depletion but due to other mechanisms. There is no evidence that 31P NMR spectroscopy presents remarkable advantages for clinical purposes compared to well established diagnostic methods.

Aged↗
PubMed1991

[Pharmacokinetics of bendamustin (Cytostasan) in B6D2F1-mice].

The pharmacokinetics of bendamustine, (1; Cytostasan), an alkylating antineoplastic agent of the N-lost group, was investigated in B6D2F1 mice. After i.v. injection of the maximally tolerated dose of 50 mg/kg a rapid decrease of the unchanged drug in plasma (MRT 21.9 min) and slowly decreasing levels of mono-, dihydroxy and beta-hydroxy-1 were observed. Variations of the age of the animals as well as of the dose administered did not alter the short MRT of 1. 1 is excreted via the kidneys to a considerable extent showing a similar metabolite pattern in urine as in plasma. The absorption of the drug from the gastrointestinal tract is incomplete resulting in an absolute bioavailability of about 40%.

Administration, Oral↗
PubMed1991

[Fetal echocardiography: Part III. Fetal arrhythmia].

The paper is a review of cardiac arrhythmias, as the most common cardiological symptom in the fetus. After exposing the basic knowledge of fetal pathophysiology necessary for the better und understanding of cardiac rhythm disturbances in the fetus, the classification of fetal arrhythmias is presented. The possibilities of modern diagnosis and differential diagnosis, such us the fetal ECG, the control of the heart rate patterns and the sonography are discussed. The usefulness of the real-time-directed and color-coded M-Mode-echocardiography in the diagnosis and classification of arrhythmias are emphasized as well as the significance of the intracardiac Doppler and simultaneous Doppler recordings in the inferior vena cava and aorta. The indications, ways and drugs used in the intrauterine therapy of arrhythmias are presented. The differentiated management related to the diagnosis is described, after reporting about our own experience with 261 fetuses with arrhythmias (27 tachycardias, 21 bradycardias and 213 ectopic beats).

Anti-Arrhythmia Agents↗
PubMed1991

Quality aspects of fibrinolytic agents based on biochemical characterization.

The purity, composition and in vitro fibrinolytic activity of four commercially available fibrinolytic agents, alteplase (recombinant tissue plasminogen activator, rt-PA, Actilyse; CAS 105857-23-6), streptokinase, urokinase and anistreplase (ansioyl-plasminogen-streptokinase activator-complex, APSAC), have been compared in this investigation. The fibrinolytic activity was measured in an in vitro thrombolytic assay. In this assay a human blood thrombus is dissolved in an environment of human plasma. This assay is representative for the in vivo situation, where plasminogen activation is also a limiting step in thrombolysis. In the in vitro thrombolytic assay alteplase is about 10 times more effective in clot lysis than either streptokinase or urokinase and more than 300 times more active than anistreplase. In addition, the ratio of active ingredient to total protein content in the preparations was analysed by RP-HPLC, SDS-PAGE, GPC-HPLC and amino acid analysis. The portion of active ingredient per total protein was 99.9% for alteplase, 55% for anistreplase, 20% for urokinase and 1% for streptokinase. This demonstrates that alteplase is the only fibrinolytic agent tested which is essentially free of protein additives of human origine and potential contaminants associated therewith. The superior purity of alteplase compared to the other fibrinolytics was confirmed by SDS-PAGE, RP-HPLC, and HPLC-GPC. Significant levels of aggregates were detected in streptokinase and urokinase preparations, whereas alteplase and anistreplase were essentially free of aggregates. These data demonstrate that there are significant differences in composition, purity and in vitro activity between different fibrinolytic agents.

Amino Acids↗