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Biomedical subjects

H Sterz

Publications and source records attributed to H Sterz.

At least 19 recordsLinked to original sources
PubMed1991

Genesis and systematization of cardiovascular anomalies in murine trisomy 16.

On account of genetic homologies trisomy 16 in the mouse is regarded as an animal model of Down's syndrome. A detailed evaluation of the cardiovascular system in 109 fetuses with trisomy 16 and 422 balanced siblings was performed in order to systematize the cardiovascular anomalies and to elucidate the pathogenetic mechanisms responsible for their formation. 92% of fetuses with experimentally induced trisomy 16 exhibited cardiovascular anomalies. The most common types of anomalies were hypoplasia and aplasia of the aortic arch, which appeared in 85% of the fetuses. Situs inversus of the aortic arch system was remarkably frequent (20%). Hypoplasia or aplasia of the pulmonary artery was seen in 10% of the fetuses. A too proximal insertion of the pulmonary artery into the ascending aorta was observed in 8% of the fetuses.

Animals↗
PubMed1989

Defects of skeletal morphology, density, and structure in mouse fetuses with trisomy 16.

Skeletal anomalies present in trisomy 16 in the mouse--an animal model of human trisomy 21--are described. Altogether 27 fetuses with trisomy 16 and 118 chromosomally balanced siblings were examined radiographically and by alizarin staining on day 20 of gestation; the radiographs were analyzed by computer-aided densitometry and structural differentiation. Extensive asymmetry or abnormal fusion of the vertebral centers and alterations of the vertebral arches were observed along with rib malformations (rib-vertebra syndrome). The skull primarily exhibited anomalies of the occipital bone. Ossification of the humerus, femur, and tibia was characterized by reduced mineralization. Typical, fracture-like alterations affecting only the tibia were also observed. Measurement of the lengths of the humeri of fetuses of comparable weight revealed a growth retardation not correlatable with the degree of mineralization. The significance of these skeletal abnormalities with regard to the trisomy 21 syndrome is discussed.

Animals↗
PubMed1989

Pharmacokinetics of picumast after administration of 14C-picumast dihydrochloride in dogs, rats, rabbits and monkeys.

In dogs, rats, monkeys and rabbits, picumast (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarin ) is eliminated from the plasma by metabolic clearance. Its main metabolic pathway is oxidation of the 3-methyl group of the coumarin ring. After oral administration, the parent compound accounted for less than 15% of the concentration of radioactivity in the plasma. In rats the hydroxylation product M2 was the main metabolite in the plasma; in the other species it was the carbonic acid M1. The hydroxylation of picumast was highly saturable, whereas further oxidation was independent of the dose in dogs and only slightly dose-dependent in rats. Picumast, M1 and M2 are pharmacologically active and potentially toxic. The sum of all three was defined as active compounds. The renal clearance of the active compounds, particularly of picumast, was very low. The terminal half-lives of the active compounds varied between 11 h in rats and 26 h in monkeys. The low plasma concentrations of other metabolites are at least partly due to their renal clearance. In dogs the bioavailability of the parent compound was 14%, the absorption of radioactivity 68%. Of radioactivity injected intravenously 54.8% was recovered from the faeces, 21.8% from the urine. The minimum toxic plasma concentrations of the active compounds were calculated from the minimum toxic dose (MTD) found in chronic or reproduction toxicity studies and the ratio Cl/f of total body clearance/bioavailability determined in the present investigations. The results showed that the differences between the MTDs in dogs and rats and on administration in rats by gavage or in the diet are largely due to differences in total body clearance and bioavailability.

Absorption↗
PubMed1988

[Angina pectoris].

Coronary heart disease has many different clinical courses: it can cause rhythm-disturbances, sudden death, pump-failure, no pain at all (silent ischemia) or typical angina. Heart-pain can occur "on demand" after physical or mental stress with a duration of 3 to 5 minutes with typical location and good response to nitrates. It also can cause atypical forms of angina such as angina on rest, mostly due to coronary spasms. Angina can stable over months and years but can suddenly increase in severity and duration. This form is called unstable angina, which has to be recognized as soon as possible since acute myocardial infarctions evolve rather frequently. Infarction is an irreversible myocardial damage but before it develops many measures can be taken to preserve the jeopardized myocardium. The recognition and differentiation of angina pectoris is therefore of utmost importance.

Angina Pectoris↗
PubMed1988

[Long-term ECG as a decision aid in indications for a permanent pacemaker].

Holter-monitoring is an excellent tool for diagnosing temporary rhythm-disturbances especially as regards brady- and tachycardias which may benefit from pacemaker-implantation. In bradycardias AV-blocks of 2nd and 3rd degree which occur only temporarily as well as bi- and trifasciculate blocks with occasional bradycardias can be analysed by Holter-monitoring. The type of pace-maker can be determined more easily by knowing whether there is temporary atrial flutter or fibrillation since DDD-pacers are not indicated in such cases. In tachycardias Holter-monitoring is also very helpful especially in detecting premonotory extrasystoles which occur occasional or in couplets or triplets or with an R- or T-phenomenon. Early treatment with antiarrhythmics eventually combined with a pacemaker can give good results for the patient. In some cases an external pacer combined with antiarrhythmics can be used as a test before permanent implantation will be performed. Also the type of antitachycardia-pacers can be determined more easily by knowing the results of Holter-monitoring.

Arrhythmias, Cardiac↗
PubMed1987

[Rapid transesophageal and transvenous atrial stimulation].

Rapid atrial stimulation (RAS) is a very effective method of treatment of paroxysmal supraventricular tachycardia (PSVT). Substained AV nodal reentrant PSVT could not be terminated by administration of different antiarrhythmic drugs in 19 patients. Transesophageal pacing was performed in 10 patients successfully - in 2 patients following verapamil intravenous administration. In the remaining 7 patients in whom this procedure failed the PSVT could be terminated by transvenous RAS - in 3 patients following the intravenous injection of verapamil.

Combined Modality Therapy↗
PubMed1987

[Angina pectoris as the leading symptom of coronary heart disease].

Coronary heart disease can be "silent" but also show arrhythmias, congestion and angina. The characteristics of angina in regard to their localisation, length of time, time of occurrence, provocation and influence by drugs are described. The treatment in emergency situations is outlined.

Angina Pectoris↗
PubMed1987

Genesis and systematization of cardiovascular anomalies and analysis of skeletal malformations in murine trisomy 16 and 19. Two animal models for human trisomies.

On account of genetic homologies, trisomy 16 in the mouse is generally regarded as a direct animal model of Down's syndrome. Mouse trisomy 19, on the other hand, can be seen as a general model of human trisomies. A detailed evaluation of the cardiovascular system and skeleton in 109 fetuses with trisomy 16 and 422 balanced siblings was carried out in order to systematize the cardiovascular anomalies and the pathogenetic mechanisms responsible for their formation according to (1) general retardation, (2) genetically determined impairment of neural-crest cell migration, and (3) direct gene action on organogenesis. Skeletal malformations in the form of a rib-vertebra syndrome encountered in Ts 16 are described here for the first time. In 108 fetuses and 219 neonates resulting from cross-breeding to induce trisomy 19, we found no significant increase in the frequency of the foregoing anomalies. These results are discussed with regard to a chromosome-specific genetic influence as opposed to a general effect of chromosome imbalance. The specificity of the Ts16 syndrome is compared with that of individual organ anomalies as can be induced by teratogenic agents. Our investigation shows that specific malformation patterns of a particular type can be produced by a variety of methods. However, the overall patterns of the two syndromes are highly chromosome-specific. On detailed examination, the malformation pattern of mouse trisomy 16 shows significant similarities with that of human trisomy 21.

Animals↗
PubMed1987

Teratologic studies on the Himalayan rabbit: new aspects of thalidomide-induced teratogenesis.

The aim of our study was to determine the period of maximum sensitivity for the induction of characteristic malformations with thalidomide (TH) in Himalayan rabbits. TH was administered orally in different doses (50, 100, 150 and 200 mg/kg) four times at 24-h intervals starting at 192 h of gestation. The malformations affected various organs: renal defects (dysplasia) and limb anomalies (dysmelia)--which had never occurred spontaneously in this strain--appeared as dose-dependent effects of the drug. By administering single doses of TH (200 and 300 mg/kg body wt) between hours 192 and 264 of gestation, we discovered the different periods of maximum sensitivity for induction of renal dysplasia (clearly prior to the 220th h of gestation) and dysmelia (between hours 230 and 240 of gestation). The types of limb malformations that we observed in the rabbit were identical to those produced in man following the intake of TH. Three doses of TH (300 mg/kg each) given between hours 222 and 228 of gestation produced characteristic limb malformations in 9 of 11 litters treated. These results make it possible to conduct in vivo experiments on a readily available laboratory animal with minor drug exposure of the gravid dam and under avoidance of toxic side effects.

Animals↗
PubMed1986

Synthesis, antitumor activity, distribution and toxicity of 4-[4-[bis(2-chloroethyl)amino]phenyl]-1-hydroxybutane-1 1-bisphosphonic acid (BAD), a new lost derivative with increased accumulation in rat osteosarcoma.

The aim of this study was to investigate whether the newly synthesized bisphosphonic acid-linked N-Lost derivative BAD retains bone-seeking and cytostatic properties. The paper describes experiments on mutagenicity in vitro and on toxicity in vivo. BAD is characterized by very low mutagenic activity toward histidine auxotrophic Salmonella typhimurium strains. Cytotoxic effects were tested in rat osteosarcoma and in Walker carcinosarcoma 256B. The LD50 of i.v. injected BAD was 146 mg/kg. Acute toxicity is probably caused by calcium complexing of the bisphosphonate part of the molecule. Labeling experiments showed moderate accumulation in bone and osteosarcoma, as well as in lung metastases. BAD effected high tumor growth inhibition in osteosarcoma and Walker carcinosarcoma-bearing rats and marked prolongation of survival; histologic and radiographic examination revealed rapid calcification of osteosarcoma and lung metastases. BAD-pretreatment produced protective effects against osteolysis induced by intratibially implanted Walker carcinosarcoma ascites cells. The cytostatic efficacy of equitoxic doses of BAD in rat osteosarcoma is comparable to that of dacarbazine and in Walker carcinosarcoma to that of melphalan.

Animals↗
PubMed1985

[Current state of treatment of bradycardia with various pacemaker systems].

The present state of knowledge about treatment of bradycardias with pacemakers is presented. Types of pacers as well as their coding, their differential indications for specific conditions and their complications and possibilities of controlling are described. Finally the percutaneous implantation technique for one- and two-chamber-systems with one or two electrodes via the subclavian vein is described as it was first published from this department in 1976.

Bradycardia↗
PubMed1985

A critical comparison of the freehand razor-blade dissection method according to Wilson with an in situ sectioning method for rat fetuses.

Two methods of dissecting rat fetuses are compared: the generally well-known freehand razor-blade dissection method according to Wilson and an in situ sectioning method (ISM). For this purpose the substance EGYT 1978 was used, which induces--inter alia--cardiovascular anomalies. Thirty-nine gravid rats were given either the test drug (EGYT 1978, 400 mg/kg body weight) or the vehicle orally from the 6th to the 15th day of gestation. The fetuses were assigned randomly to either dissection group. Both methods of examination revealed approximately the same number of anomalies per organ system. A comparison of the types of anomaly found showed, however, relevant differences in the nature of the changes revealed by the two methods. The in situ sectioning method was clearly superior to the freehand razor-blade dissection method for the detection of discrete anomalies of the cardiovascular system. We therefore recommend the in situ sectioning method as the method of choice for examining small fetuses from teratological experiments.

Animals↗
PubMed1985

A postulated mechanism of beta-sympathomimetic induction of rib and limb anomalies in rat fetuses.

Treatment of gravid rats (days 6-15 of gestation) with the beta-sympathomimetic doxaminol resulted in wavy ribs and bent limbs in the offspring. The fetuses also exhibited defective mineralization. These anomalies were produced by pharmacologically effective doses of the drug. Prior treatment with the beta-receptor blocker carazolol prevented their formation, so that the beta-sympathomimetic action of doxaminol is evidently a causative factor. Various hypotensive agents whose activity is not mediated by beta-receptors failed to produce abnormalities. This eliminates the possibility of a non-specific etiology such as diminished placental perfusion. The cyclooxygenase inhibitor indomethacin lowered the incidence of wavy ribs. Furosemide, a loop diuretic that stimulates renal prostaglandin synthesis, increased the incidence of abnormalities when combined with doxaminol. The nature of the anomalies found suggests that 1) fetal compression by the myometrium and 2) defective mineralization are prerequisites for their development. The first condition could be produced via the complex mechanism of beta-sympathomimetic-induced stimulation of prostaglandin synthesis. Defective mineralization can result directly from cAMP-mediated activation of osteoclasts and possibly be further promoted by beta-sympathomimetic-mediated prostaglandin action on the osteoclast. The pathological findings in the fetal rat skeleton cannot be correlated with corresponding findings in human neonates whose mothers were subjected to prolonged therapeutic uterine relaxation with beta 2-sympathomimetics, for example. Since the anomalies in the rat disappear spontaneously in the post-natal period, their clinical relevance appears to be slight.

Abnormalities, Drug-Induced↗
PubMed1985

Comparative bone analysis via inflammation-mediated osteopenia (IMO) in the rat.

Various methods exist for determination of trabecular or total bone mass in animal experiments. There is one group of simple techniques not requiring sophisticated equipment focusing on bone-calcium determination. By contrast, another group of newer methods requires complex equipment for procedures such as computerized analysis of bone X-rays or of nondecalcified bone sections. The methods of the first group require considerable time to perform, whereas those of the second group allow a great number of analyses in a short time. We have adapted the computerized techniques to the determination of rat-bone mass and then compared both types of methodology using the new animal model for pathological loss of bone mass: the syndrome of inflammation-mediated osteopenia (IMO) in rats [1, 2]. Reliable results were obtained with both approaches, but we recommend the use of one of the new techniques in cases where a large number of analyses is required.

Absorptiometry, Photon↗
PubMed1978

[Transesophageal rapid stimulation of the left atrium in atrial tachycardias (author's transl)].

A new method to interrupt atrial tachycardias is reported. With an esophageal double-electrode the left atrium is stimulated with an external pacemaker at rates of 400 per minute and with 10 to 20 mAmp; The rhythm-disturbances treated in this way were: atrial tachycardias with constant or inconstant blocks and paroxysmal supraventricular tachycardias. 7 of 9 cases reported showed positive results, i.e. electrically induced atrial fibrillation and sinusrhythm immediately or within the first hour after stopping the pacer (6) or atrial fibrillation after disconnection from the pacer at a lower heart-rate than before (1). In 2 cases the technique was applied without success. The transoesophageal rapid left atrial stimulation (oeRLAS) is painless, can be applied without sterile measures and even without X-ray-control just by observing the oesophageal Ecg. Digitalisation is unimportant. The technique described may prove useful in cases of atrial tachycardias esp; in intensive care units.

Atrial Flutter↗