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H Sinzinger

Publications and source records attributed to H Sinzinger.

At least 253 records · Page 14Linked to original sources
PubMed1991

Functional liver imaging with 99Tcm-galactosyl-neoglycoalbumin (NGA) in alcoholic liver cirrhosis and liver fibrosis.

Synthesis of 99Tcm-galactosyl-neoglycoalbumin (99Tcm-NGA), a recently described new radioligand with high specificity for hepatic binding protein (HBP), a galactose-residue specific receptor on hepatocytes, was carried out by covalent coupling of 2-imino-2-methoxyethyl-1-thio-beta-D-galactopyranoside to the primary amino groups of human serum albumin. NGA was purified by ultrafiltration and size exclusion high-pressure liquid chromatography (HPLC). Using a computer-based simulation program, time-activity data for the liver and precordium, blood radioactivity 2 min after i.v. injection of the radioligand, the association constant of 99Tcm-NGA-binding to HBP measured on human liver biopsies in vitro, and other patient-related parameters were put into a five-state non-linear model describing the pharmacokinetics of 99Tcm-NGA. By fitting the parameters of the model iteratively to the experimental data, an estimate of HBP concentration in the liver and of total liver blood flow was obtained. Using this model we studied 32 patients (53 +/- 11 years) with different clinical stages of alcoholic liver cirrhosis. Child B and Child C stage cirrhotic patients had a lower HBP concentration in the liver compared to control individuals (0.96 +/- 0.21 mumol l-1). The group with the most advanced cirrhosis (Child C stage) had a significantly lower HBP concentration (0.27 +/- 0.15 mumol l-1) than Child A patients (0.66 +/- 0.21 mumol l-1; P less than 0.01) and Child B patients (0.53 +/- 0.18 mumol l-1; P less than 0.05). In four patients with biopsy-proven liver fibrosis (0.84 +/- 0.20 mumol l-1) no difference in receptor concentration from normal individuals was estimated. Changes in liver blood flow were not significant between the groups. A direct comparison of HBP concentration estimated in vivo by 99Tcm-NGA functional imaging and HBP concentration measured in vitro on a surgically removed liver biopsy specimen from the same patient with a normal liver and liver cirrhosis showed good matching of these two values. The results suggest that in vivo estimation of HBP concentration in the liver by 99Tcm-NGA functional imaging might be a suitable method for determining liver cell mass.

Adult↗
PubMed1991

Prostaglandin E1 decreases the low-density-lipoprotein entry into rabbit arterial wall.

1. In 72 male rabbits fed a 1% cholesterol supplemented diet the effect of a 4 weeks daily infusion of prostaglandin E1 (PGE1, 20 micrograms kg-1 min-1 over 2 h) on [125I]-low density lipoprotein (LDL) accumulation (10 microCi; 0.5 mg protein ml-1) was examined versus sham-treatment after removal of the endothelium of the abdominal aorta by a Fogarthy catheter. 2. The uptake of [125I]-LDL was significantly (P less than 0.01) higher in endothelium-free aortic segments (showing the highest peak maximum at around 12 h after 125I-injection) as compared to aortic segments with endothelium intact (showing the lowest uptake of [125I]-LDL with the peak maximum at 48 h, last control time). Segments with the endothelium restored showed a similar LDL-retention curve to segments with endothelium however, being again significantly (P less than 0.01) higher. 3. PGE1-treatment caused reduction in LDL-accumulation, being significantly (P less than 0.001) pronounced in segments without endothelium and in segments with endothelium restored. 4. The findings indicate a beneficial effect of PGE1 in lipid metabolism by decreasing the LDL-influx into the arterial wall in-vivo.

Alprostadil↗
PubMed1991

Evaluation of somatostatin receptors in human cancer.

The binding of 123I-Tyr-3-octreotide (SDZ-204-090; specific activity 1 mCi/nmol), a new somatostatin-receptor binding radiopharmaceutical, to human tumour membrane fractions was evaluated in presence of unlabeled Tyr-3-octreotide and octreotide (SMS-201-995; Sandostatin). Tumour tissue was obtained intraoperatively from 15 patients with different endocrine tumours (insulinoma, carcinoide, phaechromocytoma, hypophysal adenoma) and breast cancer. In equilibrium experiments, membrane fractions (200 micrograms protein/ml) were incubated with increasing concentrations of 123I-Tyr-3-octreotide (0.03-30 nM) in presence or absence of 5 microM of unlabeled agonist. Binding capacities ranged from 1-20 pmol/mg protein (Kd 4-100 nM). The IC50 values (2.5-112 nM versus 0.02-69 nM) were different for the octreotide and Tyr-3-octreotide indicating that octreotide was the better competitor as Tyr-3-octreotide for 123I-Tyr-3-octreotide binding sites. In ductal breast cancer high numbers of in vitro binding sites for the radiolabel were found. In initial clinical studies 123I-Tyr-3-octreotide was i.v.-injected (3 mCi) to 5 acromegaly patients with hypophyseal adenomas. Following rapid uptake by the liver, positive tumour imaging was obtained in 3 patients which correlated to computer tomographic findings. Positive images were obtained just some minutes after injection. Our results support recent data suggesting that the 123I-Tyr-3-octreotide would be a suitable receptor-radiopharmaceutical for the localization of endocrine tumours.

Adenoma↗
PubMed1991

[Prostaglandin E1 in therapy of peripheral arterial occlusive disease].

The intraarterial and intravenous infusion of prostaglandin E1 (PGE1) today is well established in the therapy of peripheral arterial occlusive disease. This review summarizes the results of pharmacological-clinical studies and the influence of PGE1 on the pathomechanism of ischaemia due to its antithrombotic, leukocyte and endothelial stabilizing properties. Clinical data available on continuous and intermittent infusion for both modes of administration are critically appraised, taking into account more recent data on active metabolites.

Alprostadil↗
PubMed1991

[Risk factors of atherosclerosis: results of screening in Southern Austria].

In the western industrialized countries atherosclerosis is the leading cause of death. In this investigation serum cholesterol and blood pressure were measured in 4321 (60.9% females) inhabitants of Lower Austria. In addition, a short cardiovascular history was taken and age, sex, body weight, height and smoking habits were recorded. In the various villages the mean serum cholesterol differed considerably (194 +/- 52-244 +/- 49 mg/dl). Overall, women had a slightly, but non-significantly, higher serum cholesterol (224.0 +/- 53.5 mg/dl) than men (218.6 +/- 58.4 mg/dl). Although 2/3 of the participants showed an elevated serum cholesterol, only 6% were taking lipid lowering drugs. An age-dependent increase in cholesterol was found in women, whereas this correlation was present in men only until the age of 40. Approximately 30% of the participants reported a positive family history. A comparison with the mortality register showed a correlation between smoking and bronchogenic cancer. No correlation, however, was demonstrable between smoking and cardiovascular mortality--perhaps due to methodological difficulties. Regional analysis of the results indicates the importance of the role of local general practitioners in the prevention of atherosclerosis.

Adult↗
PubMed1991

123I-tyrosine-(A14)-insulin: preparation and preliminary clinical studies.

Insulin was radioiodinated with 123I (123I-tyrosine-(A14)-insulin) to a specific activity of 1 micrograms/mCi, corresponding to 0.025 I.U. of insulin/mCi. This preparation was used for in vitro binding experiments with adipose tissue, showing active binding to the two subunits of the known insulin receptor. In a preliminary clinical investigation, 5 adipose patients with (n = 2) and without (n = 3) diabetes mellitus Type II, were subject to in vivo injection of the same radiolabeled product using 3 mCi/patient. During the first minutes of dynamic imaging, the liver was the major organ of tracer uptake in all patients. Furthermore, the pancreas, and in one patient the kidneys, were visualised. Further studies on insulin in vivo kinetics and quantification are under way.

Diabetes Mellitus↗
PubMed1991

[Synergism of PGI2 and molsidomine in arterial occlusive disease].

In order to test the hypothesis, whether molsidomine acts as an in-vivo NO-donor, we examined the synergism of PGI2 and molsidomine in patients with peripheral vascular disease. The effect was quantified by measuring the platelet uptake at atherosclerotic lesion sites, as well as measuring the platelet survival after radiolabelling the autologous platelets with 111Indium-oxine. The combination of both substances achieved a significantly higher (p less than 0.01) benefit in comparison to single administration of either of the components. This synergism was shown via a decrease in thrombogenicity and a prolongation in platelet survival. These data indicate that a potentiating synergism of hemostatic regulation can be achieved via an in-vivo interaction between NO and PGI2.

Arterial Occlusive Diseases↗
PubMed1991

[Syndrome X].

Explore the source record for details and available documents.

Diabetes Mellitus↗
PubMed1991

13,14-dihydro-PGE1, an in-vivo metabolite of PGE1, decreases mitotic activity induced by corticosteroid administration.

PGE1 has antimitotic activity by virtue of its effect in increasing cAMP in vascular smooth muscle cells. The present study compares the effect of 13,14-dihydro-PGE1 (13,14-DH-PGE1) with PGE1 in an experimental model of stress induced by desoxycorticosterone in the rabbit. 13,14-DH-PGE1 significantly inhibited the stress-induced increase in mitotic activity, measured by autoradiography as percentage of 3H-thymidine positive cells, in all 3 abdominal aortic wall layers. Administration prior to stress was more effective than after stress, while combined administration was most effective. 13,14-DH-PGE1 exerts approximately 90% of the antimitotic activity of PGE1. It seems possible that the antimitotic activity observed after administration of intravenous PGE1 is attributable in part to 13,14-DH-PGE1.

Alprostadil↗
PubMed1991

[Effect of bezafibrate in isolated hypercholesterolemia and mixed hyperlipidemia on infarct risk (Stepwise Program for Individual Risk Identification and Therapy): an open multicenter study].

The therapeutic effect of bezafibrate (1 x 400 mg/day) on plasma lipids and coronary risk was evaluated in an open, prospective multicenter study in 763 patients with isolated hypercholesterolemia or mixed hyperlipidemia. During the 16 weeks of treatment (712 patients were included in the evaluation) bezafibrate lowered total cholesterol (C) by 22%, triglycerides (TG) by 32% and LDL-C by 20% and increased HDL-C by 29.6%. The ratio of C/HDL-C decreased from 8.8 +/- 2.0 to 5.4 +/- 1.5, i.e. a reduction of 36%. A comparable hypolipemic effect of bezafibrate was seen in all the subgroups of isolated hypercholesterolemia (C -21%, LDL-C -31%, HDL-C + 28%, TG -10%) and mixed hyperlipidemia (C -22%, LDL-C -16%, HDL-C + 30%, TG -37%). During treatment the coronary risk factor estimated by the SPIRIT calculator decreased from 5.5 to 2.5 (-54.5%) in male patients (n = 499). The calculated incidence of myocardial infarction thereby decreased from 225.7 to 111.9 (-50.4%). This study shows that bezafibrate effectively improves lipid metabolism in both isolated hypercholesterolemia and mixed hyperlipidemia and results in a decreased coronary risk.

Adult↗
PubMed1991

Quantification of human hepatic binding protein (HBP) via 99mTc-galactosyl-neoglycoalbumin (NGA) liver scintigraphy.

99mTc-galactosyl-neoglycoalbumin (99mTc-NGA) was synthesized by covalent coupling of 2-imino-2-methoxyethyl-1-thio-beta-D-galactopyranoside to the primary amino groups of human serum albumin. Injection of 99mTc-NGA (150 MBq; 3.5 mg (= 50 nmol)/ml demonstrated the liver to be the exclusive site of tracer-uptake. Simulation of 99mTc-NGA-kinetics allowed quantification of binding to the hepatic binding protein (HBP). Using this model we studied 250 patients with various liver disease. In alcoholic liver cirrhosis such patients with Child B and Child C stage cirrhosis had a lower HBP-concentration in the liver compared to control individuals (0.85-1.2 mumol/l). The group with the most advanced cirrhosis (Child C stage) had a significantly lower HBP-concentration (0.20-0.45 mumol/l) than Child A patients (0.60-0.85 mumol/l; p less than 0.01) and Child B patients (0.45-0.60 mumol/l; p less than 0.05). In patients with biopsy proven liver fibrosis (0.80-1.22 mumol/l) no difference in receptor concentration to normal individuals was estimated. Patients with recently diagnosed acute viral hepatitis underwent repeated 99mTc-galactosyl-neoglycoalbumin (NGA) scanning of the liver during the course of the disease. Return of liver function tests to normal values was associated with an increased hepatic imaging size as well as increase in HBP-concentration (up to a 3-fold of initial concentration). In patients exhibiting a prolonged course of the disease changes in NGA-kinetic data were borderline and the hepatic image size unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1991

Low density lipoprotein receptors: preliminary results on "in vivo" study.

Plasmatic levels of low density lipoproteins (LDL) are regulated by the receptor pathway and most LDL receptor are located in the liver. A receptor defect due to genetic mutations of the LDL receptor gene is the cause of familial hypercholesterolemia (F. H.), a disease characterized by high cholesterol levels and premature atherosclerosis. Injection of autologous radiolabelled LDL, followed by hepatic scintiscanning, can be used to obtain "in vivo" quantification of hepatic receptor activity, both in normal and hypercholesterolemic patients. In this study we observed no hepatic increase of radioactivity in patients affected by F. H., confirming the liver receptor defect. Scintigraphy is a non-invasive technique which can be used to diagnose this disease and to monitor the efficacy of hypolipidemic therapy.

Humans↗
PubMed1991

Indium-111-labeled low-density lipoprotein binds with higher affinity to the human liver as compared to iodine-123-low-density-labeled lipoprotein.

The interaction of 111In-low-density lipoprotein (LDL) and 123I-LDL with human liver-plasma membranes was investigated and compared. LDLs were isolated by sequential ultracentrifugation and radiolabeled either with 123I (using lodogen or iodine-monochloride) each followed by purification with gel-chromatography or dialysis) or 111In (using cyclic DTPA-anhydride). LDL concentrations of 0.1 to 32 micrograms protein/ml were used for direct binding assays investigating the specific binding of labeled LDL (in the presence of a 50-fold excess of unlabeled LDL) to human liver apoB-receptors. In separate experiments, displacement of bound 111In-(123I)-LDL by unlabeled LDL was studied. Human liver plasma membranes bound 239 +/- 26 ng protein of 111In-LDL/mg protein and 148 +/- 18 ng protein of 123I-LDL/mg protein specifically (p less than 0.001). The corresponding dissociation constants were 0.6 +/- 0.2 and 1.2 +/- 0.7 micrograms protein/ml, respectively (p less than 0.001). The capacity of unlabeled LDL to displace bound 111In-LDL was four times higher than that for 123I-LDL (IC50: 1.7 +/- 0.7 versus 7.7 +/- 1.0 micrograms protein/ml). No significant differences among the different methods of iodination of LDL were found. The findings show that 111In-labeled lipoproteins might be a better ligand for lipoprotein-receptor binding studies as compared to radioiodinated lipoprotein products.

Adult↗
PubMed1990

Autologous platelet-labeling in thrombocytopenia.

Field studies performed with peripheral platelets obtained from 6 male volunteers aged 23 to 29 years revealed an extraordinary dependence of labeling efficiency on incubation time and platelet concentration after 111In-oxine platelet labeling. Since the monitoring of in vivo-platelet function in patients with thrombocytopenia may cause problems due to insufficient labeling results and homologous platelets may show a different in vivo behaviour to autologous ones, we have searched for the minimal amount of platelets necessary to allow appropriate labeling and imaging in patients with thrombocytopenia. In 15 patients with untreated thrombocytopenia aged 14 to 79 years demonstrating a mean peripheral platelet count of 2.509 +/- 1.45 x 10(4) cells/microliters autologous 111In-oxine platelet labeling was performed. The results indicate that approximately 1 x 10(8) (concentrated) platelets/ml are necessary to obtain an adequate labeling efficiency and recovery. This platelet concentration can be easily achieved by drawing one more Monovette of whole blood per each 5 x 10(4) platelets/microliter peripheral platelet count less than 2 x 10(5)/microliter. It is concluded, that calculation of the required number of platelets in advance, variation of the blood volume drawn and the volume of incubation buffer allow informative, qualitative and quantitative results using autologous platelets. The method presented effectively circumvents the requirement of homologous platelets for radiolabeling in thrombocytopenia.

Adolescent↗
PubMed1990

[Atherosclerosis Risk Factors Intervention Study Strass (ARIS)].

Mortality due to cardiovascular disease in Austria amounted to 53.7% of the overall mortality in 1986. Elevated cholesterol, cigarette smoking and hypertension are the main risk factors. In order to estimate the prevalence of these risk factors and to evaluate the effectiveness of intervention strategies, we started the ARIS (in Strass, Lower Austria) in 1987/88. 568 participants (56.7% female, 43.3% male) were asked some questions concerning their cardiovascular status; blood pressure and 22 laboratory parameters were measured (including the serum lipid profile). Doppler sonography of the carotid arteries was performed in participants older than 60 years of age (n = 229). The mean values were: cholesterol: 220.3 +/- 45 mg/dl, systolic blood pressure: 147 +/- 45 mmHg, diastolic blood pressure: 88 +/- 29 mmHg. The percentage of smokers was 18.7%. A positive family history of coronary heart disease was reported by 32.7%. Stenosis (greater than 50%) of the carotid artery was discovered in 7 cases. After this initial examination we started an information campaign at regular two-monthly intervals with around 100 participants a time. As a first result a changed consumer behaviour was observed with respect to foods. The effectiveness of the intervention trial will be seen on evaluation of annual follow-up examinations over a 10-year period in the first place.

Adolescent↗
PubMed1990

Decreased prostaglandin-I2 stability in acute myocardial infarction.

It has been demonstrated that under certain conditions the in-vitro half-life of biologically active PGI2 in plasma is extremely shortened, which may result in-vivo in a local haemostatic imbalance. In 36 patients suffering from acute myocardial infarction a sequential change in in-vitro half-life of synthetic PGI2 was therefore studied during 3 weeks. 21 patients admitted turning out not to develop myocardial infarction served as follow-up controls. During and shortly after the acute episode the plasmatic half-life of PGI2 in-vitro was shortened by about 40%, improving continuously thereafter. No certain influence of either risk factors, sex or age could be discovered. A possible influence of various drugs administered in the hospital period has been excluded in 43 patients with proven coronary artery disease. No such changes occurred during acute angina pectoris attack in 12 patients. It remains to be established, whether the short-lasting destabilisation of PGI2 may be an acute disease-associated finding, or an important pathogenetic factor.

Aged↗