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Biomedical subjects

P Probst

Publications and source records attributed to P Probst.

At least 55 records · Page 3Linked to original sources
PubMed1995

[Change in the patient profile in coronary heart disease at the time of initial evaluation with coronary angiography between 1975 and 1989].

BACKGROUND AND METHOD: After the introduction of coronary angioplasty in the late 1970s, diagnostic coronary angiography has been performed for reasons other than to evaluate patients for bypass surgery. The aim of this study was to evaluate the change of the patient-profile at the time of the first angiographic evaluation of coronary artery disease. Therefore, 6456 patients in the period from 1975 to 1989 were included. RESULTS: The observation period of 15 years was divided into three parts of 5 years each (group 1 1975-79, N = 1130); group 2 1980-84, N = 2412; and group 3 1984-89, N = 2914). The mean age (53.3 +/- 7.4 vs. 54.4 +/- 8.4 vs. 57.8 +/- 9.3; p < 0,0001) as well as the number of patients of age > 64 years (6.4% vs. 9.6% vs. 25.9%, p < 0.0001) increased significantly over the 15 years. Women were found twice as often in group 3 vs. group 1 (10% vs. 16% vs. 19%; p < 0.0001). In the observation period the left ventricular ejection fraction (51.1 +/- 15.9 vs. 53.8 +/- 14.4 vs. 55.4 +/- 16.2) and one-vessel disease (37.2% vs. 38.2% vs. 42.4%) increased significantly (p < 0.0001), whereas multi-vessel disease decreased (57.7% vs. 56.6% vs. 52.6%). CONCLUSION: Between 1975 and 1989 significantly more women, more patients over 64 years of age, and more patients with lower degree of coronary disease were first evaluated with coronary angiography. The change of patient-profile may have been influenced by increased risk-factors among women and the possibility to offer patients an alternative therapy to bypass surgery.

Adult↗
PubMed1994

Genomic organization and DNA sequence of the human catecholamine-sulfating phenol sulfotransferase gene (STM).

The human monoamine neurotransmitter-preferring phenol sulfotransferase (M-PST) plays an essential role in the sulfation of catecholamines, such as dopamine. The cDNA encoding M-PST has been reported, and we have recently identified cosmid clones from human chromosome 16p11.2 for this gene, STM. Plasmid subclones derived from the STM cosmid clones were subjected to dideoxynucleotide chain termination sequencing to determine the genomic organization and DNA sequence of STM. The gene encoding full-length STM is approximately 6.4 kb and contains 8 exons and 7 introns.

Animals↗
PubMed1994

Mapping of two phenol sulphotransferase genes, STP and STM, to 16p: candidate genes for Batten disease.

The cytosolic phenol sulphotransferase gene (STP) was mapped to a region of chromosome 16, within the interval defined by human-rodent somatic cell hybrid breakpoints CY160(D) and CY12, which contains FRA16E. YAC and cosmid clones from this 16p interval were screened for the presence of STP. Two non-overlapping cosmid contigs were identified which contain STP-like sequences. Sequencing of these STP-like sequences confirmed that STP is contained within contig 343.1 and maps proximal to FRA16E, and that a related sulphotransferase STM, encoding the catecholamine-sulphating enzyme, is contained within contig 55.4 and maps to the adjacent hybrid interval CY12-CY180A. Thus two phenol sulphotransferase genes (STP and STM) have been finely localised to chromosome 16p12.1-p11.2, to the same region as CLN3, the gene for Batten disease. Both genes are therefore candidate genes for Batten disease.

Animals↗
PubMed1994

Role of bacteria-specific T cells in the immunopathogenesis of reactive arthritis.

Reactive arthritis is a usually self-limited sterile inflammation of joints that follows certain bacterial gastrointestinal or urogenital infections. The immunopathogenesis involves CD4+ T cells, which mediate an antigen-specific TH1 response to bacterial constituents within the joint. Properties of the arthritogenic bacteria and the physicochemical characteristics of the bacterial antigens may contribute to the development of reactive arthritis.

Animals↗
PubMed1994

Statistical analysis of invasive cardiology for Austria in 1992 as an approach to quality assessment.

Quality Control in Interventional Cardiology requires perfect documentation. We, therefore, report a mutual controlling system, which has been initiated in Austria 3 years ago. An all round inquiry within all the 28 Austrian catheterization laboratories was successful with a feedback rate of 100%, controlled by visiting the centers, random tests, and several phone calls. This year was the first time that an entire European country followed the guidelines for statistical documentation that the European Society of Cardiology has suggested. Within the year 1992, 3,780 percutaneous coronary angioplasties were performed in Austria, which is 19.7% more, compared to the year before. At the same time 18,806 coronary angiographies, 102 percutaneous valvuloplasties, and 138 electrophysiological ablations took place. Austria reached 84% of the number of angiographies and 50% of the percutaneous transluminal coronary angioplasty (PTCA) numbers, the World Health Organization (WHO) has provided for a country of 7.82 million inhabitants. One hundred and fifty-two "new devices" (stent/n = 89, atherectomy/n = 44, laser/n = 6, etc.) were used during this year, which was 4.0% of all PTCA procedures. Angioscopy (n = 11) and intracoronary ultrasound (n = 82) accounted for another 2.5% of "new devices". Complication rate was 0.48% hospital deaths, 0.93% emergency bypass surgery, and 1.88% myocardial infarction in 3,780 PTCAs. The individual data of each center were treated confidentially and anonymously and the evaluated questionnaire was sent back to the respective center only, including an individual recommendation for quality improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗
PubMed1993

Influence of cardiac output on peak t-PA plasma levels in patients receiving thrombolytic therapy with recombinant tissue-type plasminogen activator--correlation with patency rate.

We studied 35 consecutive patients with short onset of myocardial infarction who underwent thrombolytic therapy with rt-PA at a standard dosage regimen of 100 mg rt-PA total (10 mg given as a bolus followed by 50 mg, 20 mg and 20 mg per hour for 3 hours). These patients were monitored for t-PA antigen and t-PA activity and PAI-1 activity plasma levels during rt-PA infusion. Success or failure of thrombolytic therapy was evaluated by non-invasive criteria (early plasma creatine kinase peaks, early peak plasma myoglobin values, and electrocardiographic criteria) as well as by means of coronary angiography at the fourth day after thrombolytic treatment. In 24 (68.6%) of these patients a success of thrombolytic therapy could be established by these criteria, while 11 patients did not respond to thrombolytic therapy. Fifteen patients (14 responders and one non-responder) had to be excluded from the further evaluation because in these patients clinical laboratory data obtained upon admission before initiation of thrombolytic therapy were not complete. Therefore, 20 patients (10 responders and 10 non-responders) could further be analysed. The two groups of patients were not significantly different in body weight, body weight index, age, gender, liver or kidney functional parameters as determined before initiation of the thrombolytic therapy. Furthermore, PAI-1 plasma levels before initiation of thrombolytic therapy were not significantly different in the two groups, as were rt-PA dosage per body weight or body weight index.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Multiclonal synovial T cell response to Yersinia enterocolitica in reactive arthritis: the Yersinia 61-kDa heat-shock protein is not the major target antigen.

The T cell response to bacterial antigens plays a major role in the pathogenesis of reactive arthritis (ReA) following enteric infections with Yersinia enterocolitica. To study the antigen specificity of the T cells at the site of inflammation, the response of cloned T cells from the synovial fluid of 2 patients with ReA to partially purified antigens of Yersinia enterocolitica was determined. The clones showed different patterns of response to various fractions, indicating a multiclonal response to Yersinia antigens, and these specificities differed in the 2 patients. Some T cells were specific for Y. enterocolitica; some cross-reacted with other enterobacteria. Proteins of 14 and 19 kDa could be identified as target antigens for the T cell clones, but no clone could be unequivocally found that reacted with the highly purified Yersinia 61-kDa heat shock protein. Thus, the inflammatory T cell response in the synovial fluid in ReA is multiclonal and not predominantly directed against the bacterial heat shock 61-kDa protein.

Adult↗
PubMed1993

Identification of the Yersinia enterocolitica urease beta subunit as a target antigen for human synovial T lymphocytes in reactive arthritis.

The local T-cell response to bacterial antigens is involved in the pathogenesis of reactive arthritis (ReA). Here, we have identified a 19-kDa antigen of Yersinia enterocolitica O:9 recognized by Yersinia-specific synovial fluid CD4+ T cells in two patients with Yersinia-induced ReA. N-terminal amino acid sequencing of this protein revealed that it was identical to the 19-kDa urease beta subunit of Y. enterocolitica O:9. This protein has previously been shown to be arthritogenic in preimmunized rats after intra-articular injection. Analysis of the T-cell response to this protein showed that it contains several T-cell epitopes, one of which cross-reacts with other enterobacteria not able to induce ReA. This indicates that the arthritogenicity of the 19-kDa antigen is not a property of the 19-kDa protein alone but is dependent on its expression in bacteria able to induce ReA.

Amino Acid Sequence↗
PubMed1993

The role of type-1 plasminogen activator inhibitor in failure of thrombolytic therapy with recombinant tissue plasminogen activator.

We investigated the possible role of type-1 plasminogen activator inhibitor (PAI-1) on success or failure of thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) in 10 responders and 10 non-responders with acute myocardial infarction and early initiation of therapy within 2 h of onset using the common infusion scheme (100 mg rt-PA over 3 h). We determined plasma levels of t-PA (activity and antigen) as well as PAI-1 (activity and antigen) in samples obtained before, during and after thrombolytic treatment and compared the course of each of those parameters between responders and non-responders to therapy. Success or failure of treatment was determined by a combination of noninvasive methods and proven by coronary angiography within 5 days of initiation of thrombolysis. Thirty, 60, 90, and 120 min after initiation of rt-PA infusion, specific t-PA activities in plasma of responders were 0.62, 0.63, 0.62, and 0.57 (IU/ng/ml), respectively, as compared to 0.42, 0.42, 0.40, and 0.32 (IU/ng/ml) in nonresponders (p < 0.001). Between 4 and 8 h after initiation of therapy, a time span known to be critical for thrombotic reocclusion, specific activities were still significantly elevated in responders as compared to non-responders (p < 0.01). PAI-1 activity levels, which were not detectable during rt-PA infusion in either group, recovered to pre-treatment values 2 h earlier in non-responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

A decrease in plasminogen activator inhibitor-1 activity after successful percutaneous transluminal coronary angioplasty is associated with a significantly reduced risk for coronary restenosis.

To determine a possible relation of changes in plasma levels of plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA) to the development of coronary restenosis after successful coronary angioplasty (PTCA), we followed 104 patients with a low grade residual stenosis after PTCA (less than 30%) for a period of 12 months. PAI-1 plasma levels (functional activity) and t-PA antigen were determined 1 day before PTCA and 3 days, 3 months and 6 months thereafter. Thirty-four patients (32.69%) developed angiographically proven coronary restenosis (group A) within a time range of 4-48 weeks (median 12.5 weeks) after PTCA while the remaining patients (group B) had neither clinical signs nor angiographic evidence of restenosis after 6 months. No significant differences could be demonstrated in t-PA antigen or PAI-1 activity (plasma levels between the two groups of patients the day before PTCA). During the whole observation period t-PA plasma levels were not significantly different between the two groups; however, PAI-1 plasma levels were significantly higher at 3 months and 6 months after PTCA in patients of group A (p less than 0.005). When the pattern of PAI-1 plasma levels over time (increase or decrease between two consecutive time points of blood collection) was used to discriminate between the two study groups only 3.5-18% of patients with a decrease in PAI-1 developed coronary restenosis within the following observation period in contrast to 25-58% of patients with an increase in PAI-1 plasma levels (p less than 0.05 to p less than 0.0005).

Aged↗
PubMed1992

Predominance of Th1-type T cells in synovial fluid of patients with Yersinia-induced reactive arthritis.

The pathogenetic mechanisms underlying the development of reactive arthritis and the functional capacities of synovial T cells specific for Yersinia enterocolitica are still unclear. In this study we have determined the cytokine secretion patterns of 24 CD4+ synovial fluid (SF)-derived T cell clones from 2 patients with Yersinia-induced reactive arthritis, 16 clones specific for different Yersinia antigens and 8 clones as controls. The clones specific for Yersinia antigens predominantly belong to the T helper cell 1 (Th1) subset with production of interferon (IFN)-gamma and interleukin (IL)-2, but no IL-4, whereas SF T cells not reactive with Yersinia antigens produce IL-2, IL-4 and IFN-gamma and thus belonged to the Th0 subset. Moreover, short-term T cell lines established from SF and peripheral blood showed the same pattern. To further analyze the functional relevance of these data we investigated the influence of IFN-gamma and IL-4 on the intracellular killing of Yersinia in a human glioblastoma cell line. Our data show that the Th1 cytokine IFN-gamma promotes intracellular killing of Yersinia, whereas this effect is antagonized by the Th2 cytokine IL-4. Furthermore, the Th2 cytokine IL-10 inhibited the antigen-specific proliferative response and IFN-gamma and IL-2 production by the Th1 cells. These results provide insight into the antibacterial mechanisms at work in reactive arthritis after infection with Yersinia enterocolitica and, for the first time, reveal the cross-regulatory properties of cytokines derived from Th1 and Th2 cells in a human immune response to bacterial antigens.

Adult↗
PubMed1992

Stimulation of synovial fluid mononuclear cells with the human 65-kD heat shock protein or with live enterobacteria leads to preferential expansion of TCR-gamma delta+ lymphocytes.

T lymphocyte responses to heterologous or self 65-kD heat shock protein (hsp) have been implicated in the pathogenesis of various forms of arthritis. To delineate the relationship of 65-kD hsp to different synovial fluid (SF) T cell subsets, we stimulated synovial fluid (SFMC) and peripheral blood mononuclear cells (PBMC) from patients with different inflammatory rheumatic diseases and from healthy controls with human or mycobacterial 65-kD hsp, tetanus toxoid (TT), heat-killed or live Yersinia enterocolitica. Phenotyping of the resulting T cell lines revealed an increase of up to 97% TCR-gamma delta+ lymphocytes in the 65-kD hsp-stimulated SF-derived lines. This expansion of TCR-gamma delta+ cells was less pronounced with cultures of PBMC. A preferential expansion of TCR-gamma delta+ cells was also shown after SFMC stimulation with live, but not with heat-killed Yersinia or with TT. We conclude that a common mechanism is involved in the selective expansion of TCR-gamma delta+ lymphocytes upon SFMC infection with live Yersinia or upon contact with 65-kD hsp. Out of a panel of TCR-gamma delta+ T lymphocyte clones (TLC) derived from a human 65-kD hsp-stimulated line, only a minority of TLC proliferated weakly upon restimulation with this antigen in the presence of autologous monocytes, whereas TCR-alpha beta+ TLC responded vigorously to the human 65-kD hsp and in some cases also cross-recognized the mycobacterial hsp homologue and/or heat-killed Yersinia. This implies that additional factors or cells may be present in the milieu of SFMC cultures that propagate the expansion of TCR-gamma delta+ cells in response to 65-kD hsp or live bacteria.

Cell Line↗
PubMed1991

The influence of the presence of collaterals on restenoses after PTCA.

To assess the influence of collaterals on the long-term follow-up after successful percutaneous transluminal coronary arteriography (PTCA), 120 consecutive patients were studied. Of these, 104 (87%) had an adequate reangiogram and were included. At the time of PTCA the collaterals were estimated by a scoring system. In addition, the coronary wedge pressure was measured in 49 patients six months after PTCA, a follow-up angiogram was performed, and the patients were split up into a group with restenoses (stenosis greater than 50%), 34 patients (32.7%); and a group without restenoses (stenosis less than 50%), 70 patients (67.3%). A total of 35 patients (30.7%) had collaterals. A comparison between both groups showed no significant differences in clinical parameters (age, angina duration, vessel involvement, lipids, blood sugar, and blood pressure), and stenoses-related parameters (degree of stenoses, eccentricity, balloon size, inflation pressure, dissection, gradient after dilatation, and residual stenoses). Patients with collaterals had a significantly higher incidence of restenoses than those without collaterals (45.7% vs. 26.1%, p less than 0.05). Patients with wedge pressure of less than 45 mmHg (n = 30) had a significantly lower restenosis rate (23.3%) than patients with a coronary wedge pressure of greater than 45 mmHg (n = 19) (restenosis rate 52.6%). It is concluded that the presence of collaterals indicates a high restenosis rate after PTCA within 6 months.

Adult↗
PubMed1991

Synovial fluid-derived Yersinia-reactive T cells responding to human 65-kDa heat-shock protein and heat-stressed antigen-presenting cells.

Humoral and cellular immune reactions to heat-shock proteins have been implicated in the pathogenesis of arthritis. Heat-shock proteins occur in bacteria as well as all eukaryotes and have been highly conserved during evolution. Cross-reactivity between bacterial and human heat-shock proteins induced at the site of inflammation may underlie the pathogenesis of some forms of arthritis. In order to test this hypothesis, we raised and cloned a Yersinia-specific T cell line from the synovial fluid lymphocytes of a patient with Yersinia-induced reactive arthritis. From this line we obtained a CD4+ T cell clone that proliferated in response to Yersinia antigens and both to the mycobacterial and the human 65-kDa heat-shock protein. This T cell clone also proliferated in response to autologous heat-stressed antigen-presenting cells as well as to synovial fluid mononuclear cells from the inflamed joint, thus showing true autoreactivity against endogenously synthetized self-antigen. These results demonstrate the induction of an autoimmune T cell response by a natural bacterial infection and support the important role of heat-shock proteins in the pathogenesis of immune-mediated arthritis.

Adult↗
PubMed1991

Identification of a subgroup of Graves' disease patients at higher risk for severe ophthalmopathy after radioiodine.

We have analyzed retrospectively the records of 89 patients with Graves' disease who were treated with radioiodine between 1980-88 and whose ophthalmopathy was recorded in a uniform manner initially and after 5 and 12 months. Moreover information on progression of eye disease was obtained by telephone for all patients after an average of 72 months. Pretreatment endocrine ophthalmopathy (class greater than or equal to 1 of classification of American Thyroid Association) was present in 34% of the patients. Eight patients developed proptosis over 20 mm, 7 patients severe ophthalmopathy (classes 4 to 6), 5 patients required special treatment for eye disease. Among the 30 patients with initial ophthalmopathy, severe ophthalmopathy (5 of 30; p less than 0.05) and proptosis greater than 20 mm 16 of 30; p less than 0.05) developed in significantly more cases than in patients with no pretreatment ophthalmopathy. The data suggest that hyperthyroid patients with pretreatment ophthalmopathy are at risk for developing severe ophthalmopathy after 131I treatment.

Eye Diseases↗
PubMed1991

Plasma propafenone concentration in the evaluation of anti-arrhythmic efficacy.

The anti-arrhythmic drug efficacy of oral propafenone therapy (300 mg to 900 mg per day) was studied in relation to propafenone and hydroxy-propafenone plasma concentrations in 70 outpatients (46 males, 24 females, mean age 57 +/- 12 years) followed up for 24 +/- 32 months. On average 1.7 plasma concentration measurements were performed per patient. The arrhythmias were effectively controlled in 32 patients, but in another 32 patients propafenone therapy was ineffective; in six patients the evaluation was unclear. The therapy was effective in 66% of patients with ventricular premature beats, in 50% with complex ventricular arrhythmias, in 40% with ventricular tachycardia and in 20% with supraventricular tachycardia. Fifty per cent of patients with coronary heart disease and electrical disease, but only 20% with dilated cardiomyopathy and Wolff-Parkinson-White syndrome were effectively treated. Measurement of peak plasma propafenone levels performed 4.5 +/- 2 h after oral drug administration revealed no statistically significant dose-plasma concentration relation. Optimal propafenone drug efficacy was documented at propafenone plasma concentrations ranging from 0.20 to 0.60 micrograms/ml (63% of patients considered as effectively treated). There was a trend to decrease propafenone efficacy at plasma concentrations below 0.20 micrograms/ml and above 0.60 micrograms/ml. Analysis of hydroxypropafenone identified four patients as poor metabolizers with unusually high propafenone and low hydroxypropafenone plasma concentrations; only one of these four patients showed drug efficacy. Monitoring of propafenone and hydroxypropafenone plasma concentrations was a practical procedure to assess patient's compliance, to identify poor metabolizers and to guide anti-arrhythmic drug therapy.

Adult↗
PubMed1991

Determinants of subsidiary ventricular pacemaker suppression in man.

To investigate the relative contribution of the duration and rate of overdrive to subsidiary ventricular pacemaker suppression, in six patients with complete heart block after His-bundle ablation, ventricular overdrive stimulation studies were performed. The studies, which were spread over a mean follow-up period of 745 days, were carried out invasively with a temporary lead (one patient) as well as noninvasively with the implanted pacemakers and chest wall inhibition (five patients). The overdrive pacing rate was increased in steps of 10 beats/min, and the pacing duration was 15, 30, 60, 90, and 120 seconds at each level. A recovery period of 2 minutes was allowed after each overdrive stimulation. Incremental ventricular overdrive stimulation at increasing pacing durations consistently caused progressive suppression of ventricular impulse formation. Nonparametric variance analysis demonstrated a significant (P less than 0.0001) influence of both the pacing rate and duration on ventricular recovery time. Nonlinear regression showed an exponential increase in recovery time with incremental pacing rate and a biphasic increase in recovery time with incremental pacing duration. Beyond a pacing duration of 60 seconds ventricular impulse suppression was primarily dependent upon the pacing rate. A nonlinear regression model was applied to predict the number of beats required for return of the escape rhythm toward prepacing control values. The predicted maximum mean number of beats was 15.4 +/- 5.9 and independent of the rate and duration of pacing, although, the initial temporary instability of the escape rhythm was directly related to the degree of overdrive.

Adult↗