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F Schwarz

Publications and source records attributed to F Schwarz.

At least 37 records · Page 2Linked to original sources

Effects of selective and non-selective phosphodiesterase inhibitors on tracheal mucus secretion in the rat.

The present study was designed to characterize the effects of unselective and isoenzyme-selective phosphodiesterase inhibitors on airway mucus secretion. The isolated rat trachea was incubated in a modified Ussing chamber. Mucus macromolecules were metabolically labelled with 35S. The inhibitors were applied at the luminal side. The unselective phosphodiesterase inhibitors theophylline, enprofylline and 3-isobutyl-methylxanthine stimulated mucus secretion in a concentration-dependent manner with half-maximum effects (EC50 values) at 690 microM, 400 microM and 46 microM, respectively. The adenosine antagonist 8-phenyltheophylline did not significantly stimulate mucus output, suggesting a negligible role of adenosine in the cellular mechanisms of mucus secretion. Adenosine itself did not increase radiolabel output. Rolipram, an inhibitor of phosphodiesterase isoenzyme IV, and zardaverine, which inhibits the isoenzymes III and IV, increased potently macromolecule output with EC50 values of 40 nM and 6 microM, respectively. The selective inhibitors of phosphodiesterase isoenzymes III and V, motapizone and zaprinast, did not influence airway mucus release, suggesting a relatively low activity of isoenzymes III and V in glands of rat trachea. The stimulatory effect of theophylline on airway mucus secretion may contribute to its beneficial action in chronic obstructive airway disease. Our data suggest that this effect is mediated predominantly by phosphodiesterase isoenzyme IV.

1-Methyl-3-isobutylxanthine↗

[Is inpatient rehabilitation of patients with chronic obstructive lung disease (COPD) useful? Results of a prospective 1-year follow-up study].

Success of inpatient therapy for patients with chronic obstructive pulmonary disease (COPD) has been assessed in a prospective study of 54 patients (mean age = 63.8y). During hospital stay (mean duration = 27.6d) FEV1% of predicted improved from 42.5% on admission to 51.9% on discharge (p < 0.001). Quality of Life (QoL) (p < 0.05) and Health Satisfaction (p < 0.001) improved significantly. The 22 drop-outs revealed a significantly more depressive coping strategy but did not differ from the remaining 32 patients regarding lung function, sociodemographic data and QoL. One year after the hospital stay the remaining 32 patients showed a still improved FEV1% (46.4%, p < 0.05) and Health Satisfaction (< 0.05) but QoL scores relapsed to entry levels. Better pulmonary long-term effects were achieved by patients with high QoL scores on entry; subjects that tended most to wishful thinking as a coping strategy had worse pulmonary outcome.

Adaptation, Psychological↗

[Structure and structural disorder].

One of the central tasks of psychodynamic diagnosis, next to determining intrapsychic conflicts, central relational patterns, and subjective forms of experiencing is assessing the psychic structure or the structural disorder. This article develops the structure term from object relationship theoretical, ego-psychological, and self-psychological concepts of psychoanalysis. This "Structure of the self in the relationship to others" thus obtained is described with six structural criteria (self-perception, self-control, defence, object perception, communication, attachment). In order to be able to distinguish the extent and the quality of structural disorders four structure levels of integration based on psychoanalytic experience in the out-patient and the in-patient setting are differentiated. A basis for an operationalization is then made; it is made in the system OPD (Operationalized Psychodynamic Diagnostics). First studies regarding practicalibility and reliability are promising.

Communication↗

[The recanalization of chronic coronary artery occlusions: what factors influence success?].

Between January 1986 and June 1990, recanalization with guide-wire and balloon angioplasty (PTCA) was attempted in 509 patients (416 men, 93 women; mean age 57.5 +/- 9 years) with chronic coronary artery occlusions. The data recorded were analysed to determine the factors which influenced the outcome. The intervention was initially successful in 284 patients (55.8%; circumflex branch: 50%; right coronary artery: 52%; venous bypass graft: 50%; anterior interventricular branch: 64%). The success rate was markedly reduced if (1) the occlusion had persisted for more than 6 months (9.5%; P < 0.001); (2) occlusion had occurred at or after a vessel kink (28.5%; P < 0.001); (3) there had been no vessel "stump" (36%; P < 0.01) and (4) the occlusion was longer than 10 mm (40.7%; P < 0.05). The success-rate was higher if (1) intracoronary anastomoses were absent (61.2%); (2) occlusion had occurred in a straight vessel (62.6%); (3) there had been a vessel stump (64%); (4) the occlusion had persisted for less than 4 weeks (68.5%) and (5) the length of occlusion was < or = 10 mm (75.8%).-These data indicate that the success of PTCA after chronic coronary artery occlusion depended on the site of occlusion, its duration and length, absence of orthograde collaterals and the presence of a vessel stump. Knowing the extent of these factors helps in delineating the indications.

Aged↗

Randomized trial comparing two devices: the Palmaz-Schatz stent and the Strecker stent in bail-out situations.

UNLABELLED: To assess whether differences in design (geometry, flexibility) and material (electrostatic behavior) may influence the acute and late outcome following intracoronary stent implantation in the treatment of acute or threatened closure after prolonged balloon inflations, 50 patients were randomized to receive either a Palmaz-Schatz stent (n = 25) or a Strecker stent (n = 25). RESULTS: [table: see text] CONCLUSION: Both Palmaz-Schatz and Strecker stents are equally effective in restoring vessel patency in bail-out situations. The incidence of complications is high and similar for both stents if they were used after failed prolonged balloon inflations. Differences in design and material do not seem to influence the results.

Angioplasty, Balloon, Coronary↗

Verapamil treatment after coronary angioplasty in patients at high risk of recurrent stenosis.

OBJECTIVE: To evaluate the efficacy of high-dose verapamil treatment (240 mg twice daily) in the prevention of angiographic restenosis after primary successful coronary angioplasty in patients at high risk of recurrent obstruction. DESIGN: A placebo controlled, double blind trial in which patients with stable angina pectoris and patients with unstable angina or non-Q wave infarction treated with 330 mg aspirin and 75 mg dipyridamole twice daily were randomised to a verapamil group or a control group. Follow up angiography was performed 6 months after angioplasty or sooner if signs of recurrent ischaemia developed. SETTING: University department of cardiology. PATIENTS: 196 consecutive patients undergoing coronary angioplasty from the beginning of April 1987 to the end of March 1989 and meeting the selection criteria that included the presence of at least one of six predefined risk factors for restenosis. At the time of coronary angioplasty 113 patients had unstable angina or non-Q wave infarction and 83 had stable angina pectoris. RESULTS: In 89 (91%) patients in the verapamil group and in 83 (85%) control patients follow up angiograms were available. The restenosis rate was lower in the verapamil group (48.3%) than in the placebo group (62.7%) (odds ratio 0.56, 95% confidence interval (CI) 0.303 to 1.025 p = 0.059). Of the 172 patients in whom follow up angiograms were available, 24 (13 taking verapamil and 11 taking placebo) did not comply with the trial for more than 40 (34) days (mean (1 SD)). For the remaining 148 patients the restenosis rate was 47.4% in the verapamil group and 63.9% in the placebo group (odds ratio 0.52, 95% CI 0.271 to 0.993, p = 0.046). In the 97 patients with unstable angina or non-Q wave infarction the restenosis rate was not significantly influenced by verapamil (55.8% with verapamil v 62.2% with placebo, odds ratio 0.77, 95% CI 0.339 to 1.728, p = 0.520). In the 75 patients with stable angina pectoris the restenosis rate dropped from 63.2% with placebo to 37.8% with verapamil (odds ratio 0.36, 95% CI 0.137 to 0.917, p = 0.038). CONCLUSION: The observed beneficial effect of high-dose verapamil treatment on the angiographic restenosis rate in patients with stable angina pectoris and at increased risk of recurrent obstruction requires confirmation in further prospective studies.

Aged↗

Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia.

Increasing evidence suggests an important role for cytokines in the regulation of eosinophilic inflammation. In the present study we investigated the distribution of leukocytes, lymphocyte subsets, their activation state, and the cytokine profile present in BAL fluid from patients with various lung diseases associated with eosinophilia. For this purpose, we analyzed the levels of IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, GM-CSF, TNF-alpha, and IFN-gamma, as well as soluble IL-2 and TNF receptors, in concentrated bronchoalveolar lavage (BAL) fluid obtained from clearly defined patients with allergic and nonallergic asthma, eosinophilic pneumonia, allergic bronchopulmonary aspergillosis (ABPA), hypersensitivity pneumonitis, and idiopathic pulmonary fibrosis. BAL fluid from normal individuals and sarcoidosis patients was analyzed as noneosinophilic controls. BAL cytokine levels were compared with the cellular infiltrate and the activation state of CD4+ and CD8+ T cells as measured by the expression of IL-2 receptors (CD25), HLA-DR, and the very late activation antigen VLA-1. Beside the characteristic leukocyte infiltrate in the various lung diseases, all patients demonstrated significantly increased numbers of activated CD4 and CD8 T cells compared with normal individuals. The analysis of the cytokine profile present in BAL fluid revealed a T helper type 2 (Th2) cell cytokine pattern, with elevated IL-4 and IL-5 but normal levels of IL-2 or IFN-gamma in allergic asthma. ABPA patients demonstrated significantly increased levels of IL-4 and IL-5, with low but significantly elevated concentrations of IL-2 and IFN-gamma. In contrast, the analysis of the cytokine profile in sarcoidosis patients revealed a Th1 cell cytokine pattern characterized by increased concentrations of IL-2 and IFN-gamma but normal levels of IL-4 or IL-5. All other patient groups showed a cytokine pattern incompatible with a pure Th1 or Th2 cell response, because IL-5, IL-2, and IFN-gamma were found to be significantly increased. The BAL fluid analysis of the other, mainly non-T cell-derived cytokines and soluble receptors showed increased levels in all patients compared with normal individuals and may represent the ongoing inflammatory responses. In conclusion, whereas increased IL-4 levels were found only in diseases characterized by increased IgE production, IL-5 was elevated in all patients with increased numbers of eosinophils. The close correlation between IL-5 levels, number of eosinophils, and activated T cells further supports a role for IL-5 in causing tissue eosinophilia.

Adult↗

[Muscle aches and biochemical changes following a ultra-marathon in the cold--modification by diclofenac].

After the Swiss Alpine Marathon in Davos (67 km, altitude difference of 2300 m) the majority of the athletes are suffering from muscle soreness. The goal of the study was therefore to investigate muscle damage, inflammatory reactions and soreness perception during and after this ultramarathon. 27 athletes took part in the study. Creatine-kinase (CK) and C-reactive protein (CRP) were measured 24 hours before the race, immediately before and after the race as well as 2 hours, 24 hours and 48 hours, after the race respectively. Muscle soreness of the lower extremities before and during stretching were assessed at the same time points using a visual analog scale from 1 to 10 (VAS). Significant CK elevations were found in all runners ranging from 600 to 28,000 U/l. Compared to the values before and 48 hours after the start all athletes showed 24 hours after the start significantly elevated CRP values, indicating a pronounced systemic inflammatory reaction. Immediately after the race all runners reported a significantly elevated muscle soreness with maximal pain in the posterior muscles of the lower leg. In order to assess the influence of a nonsteroidal antiinflammatory agent on muscle damage, muscle soreness and inflammatory reactions 16 of the 27 runners received *Diclofenac SR. We were unable to find a difference in the mean plasma CK and CRP activity after the race between both groups, but there was a highly significant, till now to our knowledge never described correlation between the degree of muscle damage and systemic inflammatory reaction (r = 0.75, p < 0.02) in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Effect of inpatient treatment on pulmonary findings and subjective well-being of patients with chronic bronchitis].

In a prospective study, inpatient therapy results (mean duration of hospitalization 27.3 days) has been assessed in 70 patients with COPD (mean age 62.4 years). Therapeutic success was observed in the objective pulmonary parameters (an increase of FEV1 from 50.5% to 57.6%, p < 0.001) and an increase in PaO2 from 7.7 kPa to 8.5 kPa (p < 0.001) as well as an improvement in life quality established by questionnaire. The best pulmonary results were achieved by patients with least pulmonary obstruction and by those with subjective well-being on entry. Women and younger patients experienced the biggest improvement in life quality. Furthermore, there was a correlation between coping with chronic bronchitis and subjective well-being. Importantly, no correlation between changes in the objective pulmonary parameters and changes in well-being was observed; a finding which puts in question the previous rating of inpatient therapy success in COPD.

Adaptation, Psychological↗

Catalysis of a protein folding reaction: thermodynamic and kinetic analysis of subtilisin BPN' interactions with its propeptide fragment.

The in vivo folding of subtilisin is dependent on a 77 amino acid propeptide, which is eventually cleaved from the N-terminus of subtilisin to create the 275 amino acid mature form of the enzyme (Ikemura et al., 1987). We have cloned, expressed, and purified large quantities of the 77 amino acid subtilisin propeptide. This has enabled us to characterize its participation in the subtilisin folding reaction by spectroscopic and microcalorimetric methods. Unfolded subtilisin, when returned to native conditions, is kinetically isolated from its native state. Folding of subtilisin with the native calcium site-A is extremely slow even in the presence of a high concentration of isolated propeptide. The folding of a calcium-free mutant subtilisin, however, is readily catalyzed by the isolated propeptide. The propeptide-subtilisin folding reaction can be described as the following equilibrium: P(u) + S(u)<==>P-S<==>Pf-Sf<==>P(u) + Sf, where S(u) and P(u) are subtilisin and propeptide, respectively, which are largely unstructured at the start of the reaction; P-S is a collision complex of unfolded subtilisin and propeptide; Pf-Sf is the complex of folded subtilisin and propeptide; and Sf is folded subtilisin. The rate-limiting step in the folding reaction of calcium-free mutant subtilisin is formation of the initial collision complex, P-S. The rate at which P(u) and S(u) form a productive collision complex is approximately 500 M-1 s-1. The collision complex appears to be an early folding unit which, once formed, results in rapid isomerization to the fully folded complex. The rate constant for isomerization of the collision complex to the folded complex is > or = 0.5 s-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

[The long-term success after coronary angioplasty in old age].

Long-term results of coronary angioplasty (CAP) were compared between two age-groups of patients. Group 1 had 227 patients (158 men, 69 women) with a mean age of 70 (65-88) years, group 2 had 717 patients (611 men, 106 women), mean age 54 (20-64) years. Unstable angina was more common in group 1 than group 2 (48.9 vs 37.7%, P < 0.05). Multi-vessel disease was present in 50.7% of those in group 1 and 41.9% in group 2. Primary success of CAP was similar in the two groups (group 1: 88.1%, group 2: 90.5%). The long-term effect at the first follow-up angiography 3-4 months after CAP was slightly less favourable in group 1 than 2 (54.9 vs 58.3%; difference not significant). However, there were more patients with unstable angina in group 1. Thus the angiographic long-term results were worse in the older patients (44.6 vs 60.1%; P < 0.05), while there was no difference between the two groups as regards stable angina (64.7 vs 57.2%). After a second CAP (because of recurrence), the long-term angiographic effect was, if anything, slightly better in the older patients (87.0 vs 77.1%). The death-rate (cardiac causes of death) up to one year after CAP was comparable in the two groups (1.7 vs 0.8%), as was the rate of non-fatal myocardial infarction (2.2 vs 1.3%). These data indicate that clinical and angiographic long-term success after CAP is comparable in older and younger patient groups and age alone does not present a higher risk.

Adult↗

(+/-) isoprenaline revisited: adverse effects of sympathomimetics in asthma.

It is a matter of concern that regular, excessive use of contemporary sympathomimetics has been associated with morbidity and mortality from asthma. As a consequence, restrictions on sympathomimetic usage have recently been advocated in asthma management guidelines. he association between excessive use of inhaled (+/-)isoprenaline and an epidemic of asthma deaths in the 1960s provides a precedent; hence, we have reviewed the numerous clinical and experimental reports concerning (+/-) isoprenaline to provide insight into the present controversy.

Asthma↗

Anomalous bronchospasm following inhalation of (+) isoprenaline by asthmatics.

Sympathomimetics (beta-adrenergic agonists) presently used in asthma therapy comprise racemic mixtures of bronchodilator and non-bronchodilator enantiomers. In a randomized, double-blind placebo-controlled study, asthmatic subjects inhaled a nebulized solution of the non-bronchodilator (+) enantiomer of isoprenaline. Substantial decreased forced expiratory volume (FEV1) was detected in 2 patients and of the remaining 8, a single subject had increased reactivity to histamine 7 h after inhalation of (+) isoprenaline. These effects of (+) isoprenaline may contribute to anomalous effects of (+/-) isoprenaline in asthma.

Administration, Inhalation↗

Domain structure and domain-domain interactions in the carboxy-terminal heparin binding region of fibronectin.

The domain structures and stabilities of fragments isolated from the so-called 'hep 2' region of plasma fibronectin have been investigated by differential scanning calorimetry (DSC) and fluorescence spectroscopy. The 30 kDa hep-2A fragment contains three type III modules (III12 to III14), whereas the 40 kDa hep-2B fragment contains four such modules (III12 to III15). Melting of these fragments at neutral pH was irreversible and accompanied by rapid aggregation. In contrast, melting was completely reversible in 50 mM-glycine at pH 2.7, where DSC measurements revealed the presence of three independently folded domains in 30kDa hep-2A and four in 40 kDa hep-2B. That each domain represented a single module was confirmed by measurements with four single-module subfragments, all of which melted reversibly, even at neutral pH. At neutral pH in the presence of 6 M-urea, 30 kDa hep-2A melted reversibly in a sharp peak from which only two transitions could be resolved by deconvolution. Only the larger of these was stabilized by heparin and was assigned to modules III13 and III14. Upon isolation, module III13 melted at lower temperature than in the parent fragment where it is stabilized through an interaction with module III14. We conclude that all type III modules in the hep-2 region of fibronectin constitute independently folded domains. Modules III13 and III14 form a highly co-operative structure through functionally significant interactions that can be disrupted with acid or sufficient concentrations of urea or guanidinium chloride.

Animals↗

Energetics of folding subtilisin BPN'.

Subtilisin is an unusual example of a monomeric protein with a substantial kinetic barrier to folding and unfolding. Here we document for the first time the in vitro folding of the mature form of subtilisin. Subtilisin was modified by site-directed mutagenesis to be proteolytically inactive, allowing the impediments to folding to be systematically examined. First, the thermodynamics and kinetics of calcium binding to the high-affinity calcium A-site have been measured by microcalorimetry and fluorescence spectroscopy. Binding is an enthalpically driven process with an association constant (Ka) equal to 7 x 10(6) M-1. Furthermore, the kinetic barrier to calcium removal from the A-site (23 kcal/mol) is substantially larger than the standard free energy of binding (9.3 kcal/mol). The kinetics of calcium dissociation from subtilisin (e.g., in excess EDTA) are accordingly very slow (t1/2 = 1.3 h at 25 degrees C). Second, to measure the kinetics of subtilisin folding independent of calcium binding, the high-affinity calcium binding site was deleted from the protein. At low ionic strength (I = 0.01) refolding of this mutant requires several days. The folding rate is accelerated almost 100-fold by a 10-fold increase in ionic strength, indicating that part of the free energy of activation may be electrostatic. At relatively high ionic strength (I = 0.5) refolding of the mutant subtilisin is complete in less than 1 h at 25 degrees C. We suggest that part of the electrostatic contribution to the activation free energy for folding subtilisin is related to the highly charged region of the protein comprising the weak ion binding site (site B).(ABSTRACT TRUNCATED AT 250 WORDS)

Bacillus↗

[Long-term results of coronary angioplasty in relation to vessel size].

Repeat angiography was performed after 3-4 months in 927 of 1386 consecutive patients (67%) who had a successful percutaneous coronary angioplasty (PTCA) between 1986 and 1988. The degree of coronary artery stenosis was determined angiographically before PTCA, immediately after and 3-4 months later. Patients were assigned to one of four groups according to balloon diameter at dilatation: Group 1: 1.5-2.0 mm; group 2: 2,5 mm; group 3: 3.0 mm; group 4: 3.4-4.2 mm. Vessel wall proliferation occurred in all four groups after PTCA. In patients with angiographically demonstrated recurrence (first recurrence: 308 patients, second recurrence: 43 patients) another balloon dilatation was undertaken and a repeat angiography 3-4 months later. Long-term success rate (less than 50% stenosis) differed significantly according to the post-PTCA vessel diameter: 48% in group 1, 63% in group 2, 66% in group 3 and 80% in group 4 (analysis of variance: P less than 0.001). PTCA thus produces better long-term results in large than in small vessels.

Adult↗

[The results after prosthetic aortic valve replacement. What effect does old age have?].

Data were retrospectively analysed of 149 consecutive patients with aortic valve stenosis (91 males and 58 females; mean age 64 [27-86] years) who had a prosthetic valve implanted between 1986 and 1988. The overall operative mortality rate was 3.4%, the one-year mortality rate was 4.7%. Operative mortality rate for those aged 27-74 years was 1.7% (2 of 120), but 10.3% (3 of 29) for those aged 75 to 86 years (P less than 0.05). None of the patients in clinical grade III (NYHA classification) died within 30 days of the operation. Among those in grade IV the operative mortality rate was 15.8% (3 of 19) for those aged 75-86, but 4.0% (2 of 50) for those aged below 75 years (P less than 0.05). Valve replacement in symptomatic aortic stenosis with a prosthetic valve is today the method of choice. Operative mortality rate is low, even for patients of advanced age, particularly if the operation is done early.

Adult↗