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Biomedical subjects

F Jung

Publications and source records attributed to F Jung.

At least 91 records · Page 5Linked to original sources

Plateletpheresis-induced increase in platelet reactivity using different cell separators.

OBJECTIVE: Since plateletpheresis is being used increasingly, it is important to regard quality control to check health risks for donors and to exclude these. DESIGN: Controlled randomised prospective open comparative study. SETTING: Department of Transfusion Medicine of a University Clinic. PARTICIPANTS: 112 platelet donors were examined. INTERVENTIONS: Prior to and after plateletpheresis platelet reactivity was determined. The platelet concentrates in the two groups of 56 donors each were produced using either the cell separator 'CS-3000' and the collecting chamber PLT 30TM with the Omnix system (group I) or the cell separator 'AS-104' (group II). RESULTS: In group I five donors showed a pathologically increased platelet reactivity (p = 0.1297) after plateletpheresis. In group II there were 10 donors with a pathologically increased platelet reactivity (p = 0.0046) after plateletpheresis. The mean concentration of platelets was reduced by separation using the CS-3000 Omnix from 238 +/- 49 x 10(3)/microliters to 172 +/- 32 x 10(3)/microliters (68 +/- 27 x 10(3)/microliters) and from 243 +/- 53 x 10(3)/microliters to 180 +/- 31 x 10(3)/microliters (63 +/- 33 x 10(3)/microliters) using the AS-104. In the first case the platelet yield was 3.9 x 10(11) platelets/concentrate, in the latter case it was 2.9 x 10(11) platelets/concentrate. The 'CS-3000 Omnix' is significantly more effective in separating (58.4 +/- 15.5%) than the 'AS-104' with 44.2 +/- 7.2% (p < 0.0001). CONCLUSIONS: Since both donor groups were comparable regarding all factors recorded--especially the cardiovascular risk factors--the separation process could be responsible for the different traumatisation of platelets.

Adult↗

N-hydroxylation and N-dealkylation by P4502C3 of N-methylbenzamidine: N-oxygenation and N-oxidative dealkylation of one functional group.

1. The first detection of a microsomal N-hydroxylation of an N-alkylated benzamidine possessing alpha-H atoms by P450 is now reported in the present in vitro biotransformation studies. 2. The newly found metabolites, N-hydroxy-N-methylbenzamidine and N-methylbenzamidoxime, were identified after hplc separation by comparison of their retention times with those of synthetic reference compounds and by comixing methods. N-hydroxy-N-methylbenzamidine exists predominantly in the aminonitrone form and constitutes a novel type of metabolite. 3. By means of reconstitution experiments with purified P4502C3 from rabbit liver and with purified variants of 2C3 expressed in Escherichia coli, it has been shown that the N-hydroxylation and the N-dealkylation of N-methylbenzamidine are catalysed by the same P450 isoenzyme. 4. A reaction mechanism is proposed in which the P450-dependent N-oxygenations and N-dealkylation of N-methylbenzamidine are derived from a common intermediate. It is obvious that if alpha-H atoms are present N-dealkylation is observed; however, in contrast with previous concepts, N-oxygenation is also possible.

Animals↗

Influence of sonographic contrast media on microcirculation in rats.

In an open placebo-controlled study the influence of the injection of different sonographic contrast media on the microcirculation was proved. The study was performed in 7 Sprague-Dawley rats. In order to examine this query two different sonographic contrast media in comparison to agitated electrolyte solution (as the placebo) were injected into the abdominal aorta of 7 anaesthetized rats as a 2 ml/kg bolus at 10-min intervals. Examined were a newly developed agitated ultrasound solution (AK I: an aequeous solution of a vegetable phospholipid) and a radiographic contrast agent (AK II: 741 mg Ioversol or 350 mg iodine, respectively, per ml) which is used in an agitated form as ultrasound contrast agent, too. 1 min before and until 2 min after each injection the capillary perfusion of the same vessel area in the major omentum was measured (video-recording by use of intravital microscopy). The erythrocyte velocity was determined off-line by an image analysing system. Whereas the agitated X-ray contrast medium AK II decreases the mean capillary perfusion (temporary flow stagnation in single capillaries), AK I as well as agitated electrolyte solution did not influence the capillary erythrocyte velocity in the major omentum. The gaps which appeared immediately after the injection of AK I seem to have been brought about by spherosomes of AK I. Still the spherosomes are so small that they can pass through the capillaries, or if they are larger which cannot be determined using in vivo microscopy the flow force necessary for the deformation of the bubbles is so small that the capillary perfusion is not influenced. The injection of agitated AK I does not lead to significant changes of the microcirculation.

Animals↗

HES 200/0.5 is not HES 200/0.5. Influence of the C2/C6 hydroxyethylation ratio of hydroxyethyl starch (HES) on hemorheology, coagulation and elimination kinetics.

The plasma clearance of hydroxyethyl starch (HES) depends on the initial molecular weight and the degree of substitution. So far, little attention has been paid to the clinical relevance of the C2/C6 substitution ratio of hydroxyethyl starch. 10 patients with cerebrovascular circulatory disturbance received hemodilution therapy for 10 days, consisting of 10% HES 200/0.5 (mean molecular weight 200 kD, degree of substitution 0.5) with a C2/C6 ratio of 13.4. A second group of 10 patients received a starch solution with identical initial molecular weight and degree of substitution but with a C2/C6 ratio of 5.7. After the administration of a single dose, no significant differences between the two groups were observed. After repeated administration, significant differences could be detected in hemorheology, coagulation and elimination (p < 0.01). The larger C2/C6 ratio led to a higher intravascular mean molecular weight (95 vs. 84 kD), which in turn led to a higher increase in serum concentration during the therapy (14.7 vs. 8.6 mg/ml). Hematocrit was lowered more (-30.5 vs. -23.5%) and plasma viscosity was increased more. There was also a more pronounced increase in partial thromboplastin time (+30% vs. +13%) and a factor of 2 larger decrease of factor VIII/von Willebrand factor-complex (p < 0.01), which exceeded the dilution effect. The higher C2/C6 ratio of HES 200/0.5/13.4 slows down enzymatic degradation. After repeated administration of this starch, large molecules accumulate which are inefficiently degraded. The same effect has been observed after therapy with highly-substituted HES. This accumulation of large molecules leads to a beneficial longer lasting volume effect. The disadvantages include an increase in plasma viscosity and coagulation disturbances, which cannot be explained with the respective dilution effect alone. For these reasons, the C2/C6 ratio is of clinical relevance and should be included in the product labeling in the future.

Alkylation↗

Factors affecting the restenosis rate after percutaneous transluminal coronary angioplasty.

In an open study follow-up angiographies were performed independently from the clinical course on altogether 131 consecutive patients (99 men, 32 women) six months after percutaneous transluminal coronary angioplasty (PTCA). During this period patients received at least 320 mg of aspirin daily. Possible factors affecting the restenosis rate included age, sex, diabetes mellitus, arterial hypertension, abnormal lipid metabolism, smoking, dosage of aspirin administered, degree of stenosis shown by affected vessels before dilatation, number of vascular segments dilated and platelet reactivity. Restenosis was defined as a renewed narrowing of the dilated segment by 50% or more, with an increase in stenosis by at least 20%. In the present study the following restenosis rates were found six month after a primarily successful PTCA: 30% for the entire sample (39 out of 131 patients); 25% in patients with normal platelet function, 50% in those with mildly abnormal platelet function, and 60% in those with frankly abnormal platelet function; 24% in non-diabetic patients and 45% in diabetics. Analysis of the findings showed that abnormal platelet function and the presence of diabetes mellitus were the most important factors in the subsequent development of restenosis after angioplasty. The same also applied in a more restricted manner to the degree of stenosis present before angioplasty.

Aged↗

A novel myogenic regulatory circuit controls slow/cardiac troponin C gene transcription in skeletal muscle.

The slow/cardiac troponin C (cTnC) gene is expressed in three distinct striated muscle lineages: cardiac myocytes, embryonic fast skeletal myotubes, and adult slow skeletal myocytes. We have reported previously that cTnC gene expression in cardiac muscle is regulated by a cardiac-specific promoter/enhancer located in the 5' flanking region of the gene (bp -124 to +1). In this report, we demonstrate that the cTnC gene contains a second distinct and independent transcriptional enhancer which is located in the first intron. This second enhancer is skeletal myotube specific and is developmentally up-regulated during the differentiation of myoblasts to myotubes. This enhancer contains three functionally important nuclear protein binding sites: a CACCC box, a MEF-2 binding site, and a previously undescribed nuclear protein binding site, designated MEF-3, which is also present in a large number of skeletal muscle-specific transcriptional enhancers. Unlike most skeletal muscle-specific transcriptional regulatory elements, the cTnC enhancer does not contain a consensus binding site (CANNTG) for the basic helix-loop-helix (bHLH) family of transcription factors and does not directly bind MyoD-E12 protein complexes. Despite these findings, the cTnC enhancer can be transactivated by overexpression of the myogenic bHLH proteins, MyoD and myogenin, in C3H10T1/2 (10T1/2) cells. Electrophoretic mobility shift assays demonstrated changes in the patterns of MEF-2, CACCC, and MEF-3 DNA binding activities following the conversion of 10T1/2 cells into myoblasts and myotubes by stable transfection with a MyoD expression vector. In particular, MEF-2 binding activity was up-regulated in 10T1/2 cells stably transfected with a MyoD expression vector only after these cells fused and differentiated into skeletal myotubes. Taken together, these results demonstrated that distinct lineage-specific transcriptional regulatory elements control the expression of a single myofibrillar protein gene in fast skeletal and cardiac muscle. In addition, they show that bHLH transcription factors can indirectly transactivate the expression of some muscle-specific genes.

Amino Acid Sequence↗

[Autotransfusion with leap-frog technique in patients with coronary heart disease and planned aortocoronary venous bypass].

OBJECTIVE: The goal of the study is to test and control the quality of a special leap-frog technique which enables saving heterologous blood. DESIGN: In a randomized double-blind placebo-controlled study homologous blood was taken in 40 out of 100 patients with coronary heart disease before aortocoronary bypass operation. The leap-frog technique was used. Within 8 weeks 3-4 erythrocyte concentrates and 0.9-1.2 liters plasma were sampled. The volume (verum: HES 200/0.5 10%; placebo: 0.9% NaCl solution) substituted corresponding to the volume of blood donated. Each patient received 200 mg Fe2+/day p.o. RESULTS: Clinically, only patients treated with HES in stage of autologous blood sampling benefited significantly. Two patients showed adverse effects. The peri- and postoperative course was comparable. In the NaCl group one of the patients received homologous erythrocyte concentrates. None of the patients died pre-, peri- or post-operatively. CONCLUSIONS: 40% of the cardiosurgical patients could be considered for autologous blood donation. Isovolemic hemodilution with HES 200/0.5 10% was a suitable and safe measure in preoperative blood sampling. Physical exercise should be performed before and after autologous blood donation. A reduced exercise tolerance suggests that autologous blood donation should be stopped.

Adult↗

[Comparison of 2 6% middle-molecular hydroxyethyl starch solutions on elimination kinetics and flow characteristics of blood in volunteers].

OBJECTIVE: Investigation of the influence of C2/C6 occupation ratio of 2 different 6% hydroxyethyl starch (HES) solutions on elimination kinetics and blood fluidity. DESIGN: A single-blinded, prospective randomised cross-over study. SETTING: Haemostasiological-angiologic outpatient department of the university of Homburg. SUBJECTS: 6 voluntary apparently healthy subjects. INTERVENTIONS: A 500 ml infusion of 2 different HES solutions (6% HES 200/0.5 or 6% HES 200/0.62, respectively) was given intravenously within 1 h. A wash-out phase of 3 months was kept between both infusions. The concentration and distribution of the molecular weight of the intravasal HES molecules up until 24 h after the infusion as well as the blood fluidity before and after the infusion were measured. RESULTS: Besides the molecular substitution (MS), which is different for the 2 employed HES solutions, the occupation ratio of the C2 respectively C6 (C2/C6 occupation ratio) of the glucose ring influences the breakdown of the HES molecules. This influences the blood fluidity. While the decrease in haematocrit 1 h after the end of the infusion is comparable, the decrease in the haematocrit in the case of high C2/C6 occupation ratio and a high MS is maintained for a longer period of time. The increase in plasma viscosity in the case of high C2/C6 occupation ratio and high MS is more marked. CONCLUSIONS: The infusion of HES 200/0.62 leads to a significantly longer prevalence in comparison to HES 200/0.5, in combination with clearly larger degradation products in the plasma; this fact causes a more marked dilutional effect, but also a more marked increase in the plasma viscosity up to 24 h after the end of infusion. In the discussion on haemodilution therapy in patients with arterial occlusive disease the employment of HES which induces an increase in plasma viscosity is thought to be a disadvantage.

Adult↗

[Computer assisted analysis of the morphology of cutaneous capillaries in human intravital microscopy].

Reproducibility of capillaroscopic data is studied by a computer-assisted interactive quantification method. Determination of capillary tortuosity and capillary density is a quantitative method with a variation coefficient below 7%, while determination of erythrocyte column diameter has to be considered as a semiquantitative method. Problems arising during interactive evaluation as in case of bundles of capillaries or massive capillary dilatation are discussed in the paper.

Capillaries↗

Hypervolemic hemodilution with or without venesection in peripheral arterial occlusive disease stage II.

Patients with peripheral arterial occlusive disease (PAOD) and marked atherosclerosis often present concomitant diseases like coronary heart disease, cerebral circulatory disorders or arterial hypertension. Thus, the extent of hypervolemia is limited in case of an infusion treatment without venesection. Therefore, it was tested whether a hypervolemic hemodilution without venesection is superior to a dilution with venesection in multimorbid patients suffering from PAOD stage II. The colloidal iso-molar solution used was Haes 200/0.5 6%. Both forms of hemodilution were significantly superior compared to a control group well hydrated with cristalloid saline solution; all groups practised walking exercise twice a week over a period of one hour. However, hypervolemic hemodilution without venesection was only slightly better than the dilution with venesection. The walking distance in the group without venesection increased by 68.6 m (36.7%) in the group without venesection, by 59.0 (30.4%) in the group with venesection and by 33.6 m (20.1%) in the control group. The results show that the decision to perform a hyperor isovolemic hemodilution should depend on the volume tolerance of each patient.

Adult↗

[Adaptation of peripheral microcirculation in the course of pregnancy].

The present prospective study investigates the changes of the peripheral microcirculation during pregnancy and puerperium, especially in preeclampsia. Using videocapillary microscopy we investigated 30 pregnant women at 4 different times. We studied red cell velocity as well as reactivity to artificial ischaemia of capillary blood vessels. An increase of red cell velocity during the course of pregnancy of approximately 30% and a reduction near normal values within 12 weeks after delivery was demonstrated. There is an obvious decrease of vascular reactivity to ischaemia as a consequence of increasing physiological vasodilatation in pregnancy. 24 pregnant pregnant women with normal peripheral microcirculation at the beginning of pregnancy had an uneventful pregnancy but 3 out of 6 pregnant women with an obviously impaired microcirculation developed pregnancy induced hypertension. These 3 were smokers.

Adult↗

[Autotransfusion using the bocksprung technique in patients with coronary heart disease and coronary artery bypass grafting].

Clinically, only patients treated with HES in stage of autologous blood sampling benefited significantly. Two patients showed adverse effects. The peri- and postoperative course was comparable. In the NaCl group one of the patients received homologous erythrocyte concentrates. None of the patients died pre-, peri- or postoperatively. 40% of the cardiosurgical patients could be considered for autologous blood donation. Isovolemic hemodilution with HES 200/0.5 10% was a suitable and safe measure in preoperative blood sampling. Physical exercise test should be performed before and after autologous blood donation. A reduced exercise tolerance suggests to stop autologous blood donation.

Blood Banks↗

[Complications after coronary angiography and balloon dilatation].

All major complications within four weeks after diagnostic cardiac catheterization (DCCA; n = 4,778) or percutaneous transluminal coronary angioplasty (PTCA; n = 3,073) were analysed prospectively in 7,851 patients (5,769 men, 2,082 women; mean age 59.4 [16-88] years). There were 116 such complications in 114 patients, 46 (0.9%) after DCCA, 70 (2.3%) after PTCA. 76% of all complications occurred during the first two days after the procedure: bleeding in 29 patients, false aneurysms in 15, arterial occlusions in 12, venous ones in three, cerebral ischaemia in 12, fulminant pulmonary emboli in three, cardiac complications in 27, and others in 15. There were five deaths in connection with a DCCA, 18 with PTCA. Complications were twice as common in women as in men (DCCA: 1.5% vs 0.7%, P < 0.05; PTCA: 4.2% vs 1.7%, P < 0.001). Complications after DCCA were more frequent in those aged over 55 years (1.2% vs 0.3%, P < 0.05); after PTCA they were more frequent in those aged over 65 years (4.1% vs 1.3%, P < 0.05). Other risk factors for complications were: peripheral arterial occlusive disease for arterial occlusion (P < 0.001), high heparin dosage with DCCA (P < 0.05), and additional venous puncture with DCCA (P < 0.01).

Adolescent↗

The role of a PDGF-activated nonselective cation channel in the proliferative response.

Murine fibroblasts have a 28 pS calcium- and voltage-insensitive NSC that becomes quiescent at G0 arrest and is rapidly and specifically activated by PDGF. Activation is produced by the discrete loss of long channel closures. The NSC can be rapidly and reversibly blocked with the NSAID flufenamic acid, through a prostaglandin-independent mechanism. The cell cycle (not viability) is blocked concomitantly with NSC block. A somatic cell mutant with altered NSC conductance has been isolated and used to clone the genomic locus of the channel. The mutant growth phenotype adds further support to the participation of NSC conductance in cell cycle control.

Animals↗

Primary and secondary microcirculatory disorders in essential hypertension.

In this prospective cross-sectional study blood fluidity and peripheral microcirculation were measured in patients suffering from essential hypertension with and without macroangiopathy. The cutaneous microcirculation was evaluated by intravital microscopy and the intramuscular by pO2 needle electrode. Disorders in the microcirculation without macroangiopathy in the system of the feeding arteries are defined as primary microangiopathy. Disturbed microcirculation with macroangiopathy in the feeding arteries in one area but no detectable microcirculatory disorder in another region is defined as a secondary microcirculatory disorder. Of the 57 patients in this study 27 had a primary microcirculatory disorder. It was remarkable that all 27 hypertension patients had a microcirculatory disorder in the area of the skin. Intramuscular microcirculatory disorder on its own without affection of the skin was not detected in any case. An exclusively secondary microcirculatory disorder occurred in 16 patients. This study shows that 93% of the patients with long-term essential arterial hypertension have microcirculatory disorders. It is most interesting that about one-half of these hypertension patients had a primary microcirculatory disorder, i.e., no indication of a hemodynamically active stenosis was found in the large vessels.

Adult↗

Effects of garlic coated tablets in peripheral arterial occlusive disease.

For the first time, a weak clinical efficacy of a 12-week therapy with garlic powder (daily dose, 800 mg) is demonstrated in patients with peripheral arterial occlusive disease stage II. The increase in walking distance in the verum group by 46 m (from 161.0 +/- 65.1 to 207.1 +/- 85.0 m) was significantly higher (P < 0.05) than in the placebo group (by 31 m, from 172.0 +/- 60.9 to 203.1 +/- 72.8). Both groups received physical therapy twice a week. The diastolic blood pressure, spontaneous thrombocyte aggregation, plasma viscosity, and cholesterol concentration also decreased significantly. Body weight was maintained. It is quite interesting that the garlic-specific increase in walking distance did not appear to occur until the 5th week of treatment, connected with a simultaneous decrease in spontaneous thrombocyte aggregation. Therefore, garlic may be an appropriate agent especially for the long-term treatment of an incipient intermittent claudication.

Adult↗