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Biomedical subjects

K Huber

Publications and source records attributed to K Huber.

At least 73 records · Page 4Linked to original sources
PubMed2001

Impairment of the plasmin activation system in primary pulmonary hypertension: evidence for gender differences.

Primary pulmonary hypertension (PPH) is a rare disorder, with marked in-situ thrombosis of small pulmonary vessels occurring primarily in adult women. We investigated whether differences in the plasmin- and thrombin activation system are associated with the predominate affection of females. Plasma levels of plasminogen activator inhibitor type 1 (PAI-1), tissue-type plasminogen activator (t-PA), fibrinogen, thrombin-antithrombin (TAT) complexes, and prothrombin fragments (F1.2) were measured at baseline and after standardized venous occlusion (VO) in patients with PPH (24 female, 9 male). At baseline, females showed significant higher TAT levels (p = 0.05), higher t-PA antigen levels (p = 0.01) and higher fibrinogen levels (p = 0.03) with positive correlation to mean pulmonary artery pressure (mPAP), as well as nonsignificant lower t-PA activity, higher PAI-1 antigen and activity and F1.2 levels. After VO, females showed a significantly blunted increase in t-PA antigen (p = 0.01) and t-PA activity (p = 0.001), correlating with mPAP, as well as increased PAI-1 activity (p = 0.05). We hypothesize, that the observed presence of gender differences in the plasmin- and thrombin activation system in PPH leading to an antifibrinolytic/prothrombotic state might, in part, explain the female predominant incidence of this disease.

Adult↗
PubMed2001

Defective fibrinolytic states as triggers of myocardial infarction: the cardiologist's view.

Disclosure of a specific prothrombotic/antifibrinolytic state by determination of plasminogen activator inhibitor type 1 (PAI-1), tissue-type plasminogen activator (t-PA), and t-PA/PAI-1 complex levels in plasma may help to define patients at high risk of developing acute coronary syndromes. According to the mechanisms of PAI-1 up-regulation, i.e. genetic factors, an activated renin-angiotensin-aldosterone system, and other atherosclerotic risk factors (hypertriglyceridemia, insulin resistance), PAI-1 plasma levels might be reduced by the action of antidiabetic drugs, fibrates, statins, as well as by inhibitors of the renin-angiotensin-aldosterone system, and this effect might contribute to the anti-atherosclerotic and antithrombotic actions of these drugs. Moreover, PAI-1 resistant fibrinolytic agents may be beneficial in thrombolytic therapy of acute myocardial infarction.

Blood Coagulation Disorders↗
PubMed2000

["Inappropriate" thrombolysis in suspected myocardial infarct].

Thrombolysis in patients with suspected acute myocardial infarction (MI) without increase of cardiac enzymes (i.e. creatine kinase) above the normal level is a rare phenomenon which is not well described in the literature. We studied 1.077 consecutive patients admitted to the General Hospital of Vienna who were treated for suspected acute MI with thrombolytic agents between January 1992 and December 1998. In 39 patients (3.6%) MI was ruled out on the basis of persistently normal creatine kinase (CK) levels. By means of chart review and database inquiry 28 (72%) of these patients were finally diagnosed as having an acute coronary syndrome (coronary group); 11 patients (non-coronary group) had other diagnoses (pericarditis in 5 cases). Comparison of the coronary vs. the non-coronary group showed no differences in risk factors, in the history of cardiac events and vital signs at the time of admission. Statistically significant differences were found in age [61 (IQR 50-70) years in the coronary group vs. 47 (IQR 47-55) years in the non-coronary group, p = 0.009], in gender distribution (p = 0.007), in the ST-depression score [4 (IQR 1-5) mm vs. 0 (IQR 0-0) mm, p < 0.0001], in the difference between highest CK level and CK level at admission [21 (IQR 8-35) U/I vs. 0 (IQR 0-0) U/I, p < 0.0001] and in the time difference from admission to highest CK level [6 (IQR 3-10) hours vs. 0 (IQR 0-0) hours, p < 0.0001]. A trend towards more complications, i.e. pulmonary congestion, bradycardia, ventricular taycharrhythmia and in-hospital mortality (21% vs. 0%, p = 0.09) was found in the coronary group. The relatively low number of patients with "unjustified" thrombolysis does not justify the need for a change in criteria for thrombolysis. Patients of the non-coronary group may be identified by a lack in ST-depression. Moreover, patients of the coronary group may have benefitted from thrombolysis by prevention of myocardial damage.

Aged↗
PubMed2000

Electron-impact induced fragmentation of fullerene ions

The C2 fragmentation of fullerene ions C(q+)(60) (q = 1,2,3) induced by electron impact was studied for the first time. The cross sections for the loss of a C2 fragment indicate the presence of two different processes. At low electron energies the projectile electron leads to the direct excitation of the giant plasmon resonance. At electron energies larger than 100 eV the fragmentation of the fullerene ions can be described as an unsuccessful ionization. Only this second part of the cross section shows a dependence on the charge state q of the precursor ion.

Journal Article↗
PubMed2000

[Increased efficacy of thrombolytic therapy in acute myocardial infarction by improved properties of new thrombolytic agents].

Thrombolysis is a milestone in the therapy of acute myocardial infarction due to its ubiquitous availability and ease of application. The recombinant form of tissue-type plasminogen activator (rt-PA) has been proven to be superior over first generation fibrinolytic agents (streptokinase, urokinase, APSAC) with respect to efficacy and side effects and the front-loaded regimen has meanwhile become the "gold"-standard of thrombolytic therapy. Biochemically modified mutants of wild-type t-PA, e.g. r-PA (reteplase), n-PA (lanoteplase), and TNK-t-PA have altered biochemical and pharmacokinetic characteristics which make them more easy to use (as double or single bolus injection) and share a theoretical efficacy benefit. This article describes these specific characteristics focussing on clot-selectivity and PAI-1 resistance of the new mutants of wild-type t-PA and their possible clinical efficiency.

Fibrinolytic Agents↗
PubMed2000

Platelet glycoprotein Ia gene dimorphism alpha2-807 in malignant arrhythmia in coronary artery disease.

It has been shown recently that the variable expression of the platelet collagen receptor integrin alpha2beta1 predisposes to thrombotic risk on the one hand and hemorrhagic risk on the other hand. The level of expression of the integrin alpha2beta1 is genetically controlled and associated with the alpha2-807 dimorphism. The expression level of this platelet collagen receptor may play a central role in the rapidly evolving coronary artery lesions that lead to malignant arrhythmia and sudden cardiac death. We studied allelic frequencies of the alpha2-807 dimorphism for their relation as a risk factor for malignant arrhythmia in a well-defined subgroup of patients with coronary artery disease. We compared allelic frequencies (by sequence specific primer polymerase chain reaction) of the dimorphism that is associated with integrin alpha2beta1 levels in 94 Caucasoid survivors of sudden cardiac death with a matched group of 106 patients with coronary artery disease without sudden cardiac death. Gene frequencies in the patient groups did not differ and were similar to those in the general population represented by 217 healthy individuals. There was no overrepresentation of an allele in any group. The inherited dimorphism that is associated with the levels of platelet integrin alpha2beta1 is not associated with malignant arrhythmia in coronary artery disease patients.

Adult↗
PubMed2000

TrkB expression and early sensory neuron survival are independent of endogenous BDNF.

Sensory neurons initially survive independently of neurotrophins in culture during the stage of development when their axons are growing to their targets. Because mRNAs encoding brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase TrkB are detectable in subsets of sensory neurons from the earliest stages of their development, we investigated whether a BDNF autocrine loop is responsible for sustaining the survival of these neurons during this early stage in their development. Low-density dissociated cultures of nodose and dorsal root ganglion neurons were established from wild type and BDNF(-/-) mouse embryos at this stage and were grown in defined medium without added neurotrophins. Wild type and BDNF-deficient neurons survived equally well under these conditions, indicating that a BDNF autocrine loop does not play a role in sustaining the survival of sensory neurons during the earliest stages of their development. As sensory axons approach their targets, TrkB expression increases in a subset of neurons that becomes dependent on BDNF produced by other cells. Because numerous studies have shown that neurotrophins, including BDNF, increase expression of their receptors, we investigated whether endogenous BDNF is required for the increase in TrkB expression observed during stage of development. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) showed that the developmental increase in TrkB mRNA expression occurred normally in the sensory ganglia of BDNF(-/-) embryos. Taken together, our studies of sensory neuron development in BDNF-deficient embryos have demonstrated that endogenous BDNF is neither required for the early survival of these neurons nor for the induction of TrkB expression.

Animals↗
PubMed2000

Multiple ionization and fragmentation of negatively charged fullerene ions by electron impact

Cross sections for the electron-impact multiple ionization and fragmentation of negatively charged fullerene ions C(-)(n) ( n = 60, 70) to C(q+)(n-m) ( q = 1,2,3 and m = 0,2,4) have been measured for electron energies up to 1 keV. In the case of pure ionization all threshold energies are about 10 eV higher than the values expected. This shift, however, is not observed for the fragment ions. The experimental data indicate that there is no strong electron-electron interaction between the incident electron and the attached electron. A novel ionization mechanism is proposed which can be expected to be valid for all negatively charged molecular or cluster ions which are able to shield the attached electron from the incident electron.

Journal Article↗
PubMed2000

Quantitative FISH analysis and in vitro suspension cultures of erythroid cells from maternal peripheral blood for the isolation of fetal cells.

Several techniques for the enrichment of nucleated fetal red blood cells present in maternal blood have been reported. Here we describe the use of a quantitative fluorescence in situ hybridization (FISH) method and in vitro suspension cultures of erythroid cells from newborn cord blood and maternal peripheral blood. Together with a rapid high performance liquid chromatography (HPLC) method, that allows us to determine as few as 100 cells containing haemoglobin F (HbF), we have scrutinized the reported enrichment methods for fetal nucleated cells in peripheral maternal blood. One hundred FISH analyses on maternal peripheral blood were performed. The method comprises a cell lysis method for depletion of red cells with minimal losses of nucleated cells, uniform numbers of cells (750 000 cells each) on microscopic slides, and inclusion of internal controls to monitor the efficacy of hybridization. Twenty-six cultures of pure erythroid progenitor cells from maternal peripheral blood were analysed for the expansion of fetal cells. To generate these in vitro cultures, nucleated cells from 10-20 ml of peripheral blood from 26 pregnant women were grown in media containing growth factors and hormones to yield over 10(7) of immature erythroid cells within two weeks. Of those, 13 cultures were from pregnancies with confirmed male fetuses. A total of approximately 8x10(8) maternal cells were added into tissue culture medium for these 13 cultures, resulting in about 2x10(8) nearly pure erythroid cells after two weeks. Whereas fetal cells, alone or added into cultures of peripheral blood, grow rapidly and can be detected quantitatively, we could not find any fetal cells in cultures from maternal blood. Likewise, in 7.5x10(7) peripheral blood cells probed by FISH analysis (half of which were from pregnancies with male fetuses) no single Y chromosome was detected. In summary, suspension cultures of erythroid cells can be established routinely and easily. With the quantitative FISH technique used, 750 000 cells per slide can be screened reliably for cells with Y chromosomes. However, the stringent quality-criteria and most elaborate methods indicate that fetal cells in maternal peripheral blood can not be found using the current technology.

Cell Culture Techniques↗
PubMed2000

[Tonsillectomy with the argon-plasma-coagulation-raspatorium - a prospective randomized single-blinded study].

BACKGROUND: The Argon-Plasma-Coagulation (APC) offers an innovative possibility for the tonsillectomy combined with a high-frequency technology. Aim of our study was to inves-tigate the differences between this high-frequency-technology and the traditional tonsillectomy. No reports exist in the use of the APC in the tonsillectomy. METHODS: Argon-Plasma-Coagulation tonsillectomy (TE-APC) was compared with the traditional blunt dissection tonsillectomy (TE-trad) with hemostasis by compression and bipolar coagulation. 133 patients were stratified in two age groups in a clinical prospective randomised study. RESULTS: Average surgical time and blood loss were markedly decreased in the TE-APC group (p<0,01). There was no significant difference between the two techniques concerning postoperative pain, otalgia, and primary or secondary haemorrhage. In the TE-APC group more extensive fibrin layer appeared after surgery. In the TE-APC patients' group, there was a slightly higher consume of analgetics in some postoperative days. CONCLUSIONS: The one-step dissection and coagulation procedure leads to an almost bloodfree woundground and to a reduction of operation-time. The self-limited and effective coagualative properties of the APC-method leads to a controlled penetration depth. The often associated extensive post operative pain and uncontrolled tissue- damage, known from electrical and lasersurgical techniques, was not found in TE-APC-patients-group.

Adolescent↗
PubMed2000

Comparative studies on Na-dependent Pi transport in ovine, caprine and porcine renal cortex.

In contrast to monogastric species, renal excretion of inorganic phosphate (Pi) in ruminants is low and this could be attributed to an almost complete tubular Pi reabsorption. However, the functional and regulatory basis for this phenomenon has not yet been clarified. Therefore, it was the aim of the present study to characterize the kinetic parameters of the tubular Pi reabsorption system as affected by P or Ca depletion using preparations of renal cortex brush border membrane vesicles (BBMV) from goats and sheep and to compare the data with respective parameters of porcine preparations. Na-dependent Pi uptake into renal cortex BBMV as a function of Pi concentration showed typical Michaelis-Menten kinetic and respective Scatchard plot analysis of the specific Pi uptake revealed linearity indicating the predominant presence of a single type of Pi transporters in the preparations. Under control conditions Vmax values of Na-dependent Pi uptake into BBMV were highest in goats and sheep and lowest in pigs (1.98, 1.39 and 0.95 nmol x mg(-1) protein x 10s(-1), respectively). Km values were not different between goats and sheep under all feeding conditions and ranged from between 0.34 mmol x l(-1) and 0.55 mmol x l(-1) which was three- to five-times higher than that found in pigs (0.11 mmol x l(-1)). Oligonucleotides derived from rat kidney cortex type IIa Na/Pi cDNA were used for reverse transcriptase-polymerase chain reaction (RT-PCR) in goat, sheep and pig kidney cortex. The products isolated were 768 bp for sheep and pigs and 765 bp for goats, with the respective amino acids sequences, representing a segment of approximately 40% in length of the entire transporter, exhibiting an at least 92% sequence homology between different species. From the results, involvement of type IIa Na/Pi cotransport in tubular Pi reabsorption in small ruminants can be postulated. However, it should not be considered that a potential role of other Pi transport systems be completely be excluded. Interestingly, neither P nor Ca depletion caused significant effects on Na-dependent Pi transport capacities and affinities in goats and sheep. From this, parathyroid-hormone independent regulatory pathways of tubular Pi reabsorption can be assumed.

Animals↗
PubMed2000

Effects of vitamin E on chronic and acute endothelial dysfunction in smokers.

OBJECTIVES: The aims of this study were to determine whether chronic or acute impairment of flow mediated vasodilation (FMD) in the brachial artery of smokers can be restored or preserved by the antioxidant vitamin E. BACKGROUND: Transient impairment of endothelial function after heavy cigarette smoking and chronic endothelial dysfunction in smokers result at least in part from increased oxidative stress. METHODS: We studied 22 healthy male smokers (mean +/- SD, 23 +/- 9 cigarettes per day) randomly assigned to receive either 600 IU vitamin E per day (n = 11, age 28 +/- 6 years) or placebo (n = 11, age 27 +/- 6 years) for four weeks and 11 age-matched healthy male nonsmokers. Flow mediated vasodilation and endothelium-independent, nitroglycerin-induced dilation were assessed in the brachial artery using high resolution ultrasound (7.5 MHz) at baseline and after therapy. Subjects stopped smoking 2 h before the ultrasound examinations. At the end of the treatment period, a third scan was obtained 20 min after smoking a cigarette (0.6 mg nicotine, 7 mg tar) to estimate transient impairment of FMD. RESULTS: Flow mediated vasodilation at baseline was abnormal in the vitamin E (5.3 +/- 3.8, p < 0.01) and in the placebo group (6.4 +/- 3.5, p < 0.05) compared with nonsmoking controls (11.6 +/- 4.7). Using a two-way repeated measures analysis of variance (ANOVA) to examine the effects of vitamin E on FMD, we found no effect for the grouping factor (p = 0.5834) in the ANOVA over time but a highly significant difference with respect to time (p = 0.0065). The interaction of the time factor and the grouping factor also proved to be significant (p = 0.0318). Flow mediated vasodilation values remained similar after treatment for four weeks in both groups but declined faster after smoking a cigarette in subjects taking placebo compared with those receiving vitamin E (p values from successive differences for the time/group factor: 0.0001/0.0017). The transient attenuation of FMD (calculated as the percent change in FMD) was related to the improvement of the antioxidant status, estimated as percent changes in thiobarbituric acid-reactive substances (r = -0.67, p = 0.0024). Nitroglycerin-induced dilation did not differ between study groups at baseline or after therapy. CONCLUSIONS: These results demonstrate that oral supplementation of vitamin E can attenuate transient impairment of endothelial function after heavy smoking due to an improvement of the oxidative status but cannot restore chronic endothelial dysfunction within four weeks in healthy male smokers.

Adult↗
PubMed2000

The decanucleotide polymorphism in the factor VII promoter predicts factor VII plasma levels but not the risk of acute coronary syndromes.

It is known from large epidemiological studies that the elevation of coagulation factor VII in plasma is an independent risk factor for acute coronary syndromes. The level of factor VII is influenced by polymorphic sites in the factor VII gene. However, data on the association of such polymorphisms with the risk of acute coronary syndromes are conflicting. A decanucleotide insertion/deletion polymorphic site has been described in the promoter of the factor VII gene that leads to a dramatic change in the plasma factor VII levels. We therefore analyzed the association of this polymorphism with the risk of acute coronary syndromes in a case-control study. Included in the study were 111 patients with angiographically documented acute coronary syndromes and 108 age- and sex-matched individuals from the same geographic area without signs or symptoms of coronary heart disease. The presence or absence of the decanucleotide stretch at position -323 in the promoter of factor VII was monitored using a polymerase chain reaction (PCR)-based restriction technique. The prevalence of the genotype with the homozygous deletion was similar in the patients with acute coronary syndromes (79.2%) and in the control patients (79.6%). There was a non-significant trend toward a higher prevalence of the homozygote deletion in patients with premature acute coronary syndromes (77.4%) compared with an age-matched subgroup of the control patients (67. 5%) (odds ratio [OR] 1.6, confidence interval [CI] 0.95, 0.61-3.93). Thus, we could not find a significant association of the occurrence of acute coronary events with the insertion/deletion polymorphism in factor VII.

Acute Disease↗
PubMed2000

The TETAMI trial: the safety and efficacy of subcutaneous enoxaparin versus intravenous unfractionated heparin and of tirofiban versus placebo in the treatment of acute myocardial infarction for patients not thrombolyzed: methods and design.

Patients with acute myocardial infarction (AMI) who do not receive early reperfusion therapy are at high risk of reinfarction or death, and the efficacy and safety of antithrombotic therapy in this group of patients has not been evaluated. Enoxaparin is a low-molecular-weight heparin (LMWH) that has previously been shown to reduce the incidence of ischemic events in patients with unstable angina or non-Q-wave MI. The principal aims of the TETAMI study are to investigate the efficacy and safety of treatment with enoxaparin or tirofiban (a glycoprotein IIb/IIIa receptor antagonist) alone or in combination for 2 to 8 days in patients with AMI who are not eligible for early reperfusion therapy. In this 2 by 2 factorial design study approximately 900 patients will be randomly assigned, in a blinded manner, to one of four treatments: enoxaparin alone, enoxaparin plus tirofiban, unfractionated heparin (UFH), or UFH plus tirofiban, with appropriate matched placebos. The primary end point is the composite of death, recurrent AMI, and recurrent angina, analyzed at 30 days after AMI. The design and methods of the TETAMI study are described in this article.

Adult↗
PubMed2000

Effects of the 5-HT3 antagonist cilansetron vs placebo on phasic sigmoid colonic motility in healthy man: a double-blind crossover trial.

AIMS: 5-hydroxytryptamine3 receptor antagonists act antiemetically and slow colonic transit. This study evaluated effects of the high-affinity 5-HT3 antagonist, cilansetron, on fasting, meal-and anticholinesterase-stimulated phasic contractile activity of the human sigmoid colon as well as on bowel habits and stool consistency. METHODS: Five female and seven male healthy volunteers received, during three 7 day periods separated by 7 day wash-out periods, 4 mg cilansetron, 8 mg cilansetron or placebo three times daily orally under random, double-blind, crossover conditions. On day 8 of each treatment period, motility 20-40 cm from the anal verge was recorded using five pressure sensors spaced at 5 cm intervals. After a basal 30 min, subjects swallowed a further dose of the scheduled treatment; 60 min later, blood was taken for the determination of plasma cilansetron levels. Thereafter, subjects ingested a 4200 kJ meal and 250 ml sweetened mallow tea (166 kJ); 90 min after meal onset, 1 mg neostigmine was administered intramuscularly and motility recording was continued for 60 min RESULTS: Phasic contractile activity and intraluminal base-line pressure increased postprandially and more so after neostigmine. With cilansetron, the area under the pressure curve as the primary outcome variable and the number of contractions were significantly greater than with placebo (P = 0.005), amplitude and duration of contractions and base-line pressure were not affected. The effects of the two cilansetron dosages did not differ. With cilansetron, stool tended to become firmer. No adverse effects were observed. Plasma levels were highest with 8 mg cilansetron. CONCLUSIONS: Cilansetron slightly augments meal-stimulated and markedly neostigmine-stimulated phasic motility of the sigmoid colon. When administered over 7 days, it tends to increase stool consistency and is well tolerated.

Adult↗