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Biomedical subjects

R Thiele

Publications and source records attributed to R Thiele.

At least 19 recordsLinked to original sources

[Current prescription practice of CSE inhibitors at clinic discharge after acute myocardial infarct].

We investigated the use of statins in clinical practice in patients with acute myocardial infarction in Germany in 17,732 consecutively included patients of the registries MIR-1 and MITRA-1. A clinical follow-up has been performed in the MITRA-1 study after a mean period of 18 months. In total 30% of all patients with acute myocardial infarction received statins at discharge. From 1994 to 1998 the use of statins increased from 6% to 44%; however in 1998 still less than half of the patients with acute myocardial infarction received statins at discharge. In a logistic regression model, concomittant diseases as renal failure (OR 0.7), heart failure (OR 0.7) and diabetes mellitus (OR 0.9) were associated with a lower use of statins. Age > 70 years (OR 0.5) was also associated with a lower use of statins at hospital discharge. Patients with statins at discharge had a lower long-term mortality of 5.8% versus 12.9% in patients without statins. After adjustment to age and comorbidity, use of statins at discharge was associated with a borderline significant reduction of long-term mortality (multivariate OR 0.7, 95% CI 0.4-1.0). In a subgroup analysis of therapeutic benefit, measured by the "number needed to treat" (NNT), the number of patients to treat with statins to save one life, patients with cardiovascular risk factors, as heart failure (NNT 7.5), diabetes mellitus (NNT 7.8) and age > 70 years (NNT 13.8) had a larger therapeutic benefit as patients without these risk factors (NNT 345). However, these high-risk patients received less often statins than patients without risk factors (use of statins 11.8% versus 19.8%).

Aged↗

Correlations between the duration of pain and the success of shock wave therapy.

Patients who have had successful treatment for either chronic heel pain (plantar fasciitis) or humeral epicondylitis subsequently were evaluated for a comparable problem in the contralateral heel or elbow. Patients who had experienced symptoms in the contralateral heel or elbow for a shorter period were less likely to have a positive result from shock wave therapy than those patients who had received treatments for more chronic symptoms.

Adult↗

Effect of intravenous magnesium on ventricular tachyarrhythmias associated with acute myocardial infarction.

Ventricular ectopy and left ventricular dysfunction are important predictive factors for an unfavourable outcome following an acute myocardial infarction (MI). Tachyarrhythmias are a major cause of death subsequent to MI. Magnesium was postulated to have an antiarrhythmic effect after MI. Therefore we have investigated the influence of intravenous and oral magnesium (Mg) therapy on ventricular tachyarrhythmias. 67 patients with myocardial infarction (MI) diagnosed according to the WHO criteria of anamnesis, infarct-specific electrocardiogram (ECG), and enzymatic status were included in a prospective study. 23 patients (group 1) received 2 g Mg per day (= 82 mmol Mg/24 h) intravenously for the first 3 days followed by oral magnesium adipate administration of 3 x 2 coated tablets of magnesium 50 Apogepha (= 300 mg Mg/24 h or 12.34 mmol Mg/24 h, respectively) for the full duration of the study. 26 patients (group 2) received only i.v. magnesium for the first 3 days after admission (2 g Mg/24 h). The results of this treatment were compared to those of a control group of 18 MI patients without magnesium administration. All groups were identical with regard to other forms of treatment. The magnesium levels in serum and erythrocytes of all patients were measured at the following time points: days 0 (admission time), 1, 2, the day of discharge (about day 20) and after 12 weeks. The tachyarrhythmias were monitored by 24-h-continuous-electrocardiography on days 0, 1 and on the day before discharge (about day 20). The serum magnesium levels rose significantly during i.v. Mg-administration (1 and 2 day) but decreased in group 2 subsequently until the time of discharge from hospital. In contrast group 1 patients receiving oral as well as intravenous magnesium did not show this drop. The uptake of magnesium into the erythrocytes was less obvious. The erythrocyte magnesium concentration of the control group remained significantly low in serum and red blood cells. Significantly less ventricular premature beats and runs (< 5 ventricular premature beats and > 5 ventricular premature beats) compared to admission day were observed in both treated groups. These data suggest that the frequency of ventricular tachyarrhythmias is reduced by administration of intravenous magnesium and support an early high dose administration of intravenous magnesium in the wake of myocardial infarction.

Administration, Oral↗

[Coronary angiography and change in antioxidative status].

PATIENTS AND METHODS: In a prospective study in 53 patients with stable angina pectoris symptoms the antioxidant status (glutathione peroxidase, glutathione, superoxid dismutase, malondialdehyde and selenium in serum and whole blood) was determined before and 4 to 6 hours after coronary angiography. According to the results of the coronary angiography the patients were classified in a group with "severe" (n = 16) and another with "moderate" coronary alterations. RESULTS: In both groups there was a significant reduction of selenium in serum and whole blood. The enzymes glutathione peroxidase and superoxide dismutase as well as glutathione and malondialdehyde changed only slightly. CONCLUSION: These results can be the cause of an increase of the formation of free radicals during coronary reperfusion (PTCA, implantation of stents in the group with "severe" coronary alterations) but could also be seen as a sign of formation of radicals by the method itself (in patients with "moderate" coronary alterations). Further investigations are indicated. Furthermore the amelioration of the antioxidant status of the organism by scavenger substances (vitamins A, B, C and selenium) should be discussed.

Aged↗

[Effect of administration of selenium and vitamin E on heart failure and ventricular arrhythmias in patients with acute myocardial infarct].

PATIENTS AND METHOD: Patients with acute myocardial infarction were treated with selenium and vitamin E as antioxidants in addition to the standard therapy. They were compared to a reference group which received no additional therapy. It was to be investigated whether selenium and vitamin E are able to positively influence the course of the infarction, measured by way of the insufficiency symptoms, ventricular cardiac arrhythmia in long-term ECG and the ejection fraction determined by echocardiography. The concentrations of selenium, malonic dialdehyde (TBARS), glutathione peroxidase and vitamin E were measured at various points in time. RESULTS: During the course of the in-patient treatment, significant percentage increases in selenium, glutathione peroxidase and vitamin E were detected. Group differences were similarly significant. It was not possible to detect differences in the clinical parameters. Possible explanations to be discussed are the duration of the treatment, the times of the examinations and the different proportions of patients treated thrombolytically in the 2 groups.

Adult↗

Protein threading by recursive dynamic programming.

We present the recursive dynamic programming (RDP) method for the threading approach to three-dimensional protein structure prediction. RDP is based on the divide-and-conquer paradigm and maps the protein sequence whose backbone structure is to be found (the protein target) onto the known backbone structure of a model protein (the protein template) in a stepwise fashion, a technique that is similar to computing local alignments but utilising different cost functions. We begin by mapping parts of the target onto the template that show statistically significant similarity with the template sequence. After mapping, the template structure is modified in order to account for the mapped target residues. Then significant similarities between the yet unmapped parts of the target and the modified template are searched, and the resulting segments of the target are mapped onto the template. This recursive process of identifying segments in the target to be mapped onto the template and modifying the template is continued until no significant similarities between the remaining parts of target and template are found. Those parts which are left unmapped by the procedure are interpreted as gaps. The RDP method is robust in the sense that different local alignment methods can be used, several alternatives of mapping parts of the target onto the template can be handled and compared in the process, and the cost functions can be dynamically adapted to biological needs. Our computer experiments show that the RDP procedure is efficient and effective. We can thread a typical protein sequence against a database of 887 template domains in about 12 hours even on a low-cost workstation (SUN Ultra 5). In statistical evaluations on databases of known protein structures, RDP significantly outperforms competing methods. RDP has been especially valuable in providing accurate alignments for modeling active sites of proteins.RDP is part of the ToPLign system (GMD Toolbox for protein alignment) and can be accessed via the WWW independently or in concert with other ToPLign tools at http://cartan.gmd.de/ToPLign.html.

Amino Acid Sequence↗

Interruption of bronchial circulation leads to a severe decrease in peribronchial oxygen tension in standard lung transplantation technique.

OBJECTIVE: In clinical practice lung transplantation is the only procedure where the transplanted organ is left without its own arterial perfusion. With the interruption of the bronchial arteries the nutritive support is dependent on collateral flow by the pulmonary artery and the oxygen tension of desaturated central venous blood, representing an abnormal physiology. METHODS: To analyze this problem systematically, we used a standard single left lung transplantation model in the pig (n = 12). In accordance with the clinical standard, lung preservation was performed with modified Euro-Collins solution with addition of prostacycline. The duration of ischemia was set to 4 h. Before and after single left lung transplantation tissue oxygen tension in the peribronchial tissue was measured with Licox tissue pO2 microprobes. For validation, the myocardial tissue oxygen tension was recorded simultaneously. The hemodynamic assessment included continuous flow measurement of the left and right pulmonary artery using Transsonic ultrasound flow probes. After transplantation the animals were observed for 4 h. For hypothetic augmentation of collateral blood flow to the peribronchial tissue we administered Nitric oxide (10 ppm) to the ventilation in six pigs (group B). Six pigs (group A) served as a control without the addition of nitric oxide (NO). All pigs were ventilated with a FiO2 of 0.5 resulting in paO2 values between 160 and 200 mmHg. RESULTS: In both groups single lung transplantation led to a significant decrease in peribronchial tissue oxygen tension throughout the observation period. Pre-Tx values of peribronchial tissue oxygen tension (38.31 +/- 6.56 mmHg) decreased to 9.72 +/- 2.55 mmHg in group A and 10.3 +/- 3.61 mmHg in group B after 4 h, which could not be altered by a FiO2 of 1.0 (P < 0.0001). The addition of NO in group B led to a significantly augmented flow in the left pulmonary artery (0.63 +/- 0.31 l/min in group B vs. 0.46 +/- 0.26 l/min group A, P < 0.001) representing 67 vs. 49% of the pre-Tx flow in groups B and A, respectively, but the peribronchial tissue oxygen tension was not influenced (P > 0.05). In both groups A and B, the central venous pO2 did not differ in the postoperative period (41.83 +/- 3.27 mmHg group A vs. 43.26 +/- 2.98 mmHg group B) and was kept in a comparable range to the pretransplantation values (45.23 +/- 3.41 mmHg pre-Tx). CONCLUSIONS: The persistence of a very low peribronchial tissue oxygen tension in the early phase after lung transplantation cannot be influenced by improved pulmonary artery flow and solely relates to the central venous pO2, which cannot be augmented by the addition of NO. This mechanism might be a trigger for anastomotic healing problems, infectious complications and later development of obliterative bronchiolitis (OB).

Animals↗

New scoring schemes for protein fold recognition based on Voronoi contacts.

MOTIVATION: The genome projects produce a wealth of protein sequences. Theoretical methods to predict possible structures and functions are needed for screening purposes, large-scale comparisons and in-depth analysis to identify worthwhile targets for further experimental research. Sequence-structure alignment is a basic tool for the identification of model folds for protein sequences and the construction of crude structural models. Empirical contact potentials (potentials of mean force) are used to optimize and evaluate such alignments. RESULTS: We propose new scoring schemes based on a contact definition derived from Voronoi decompositions of the three-dimensional coordinates of protein structures. We demonstrate that Voronoi potentials are superior to pure distance-based contact potentials with respect to recognition rate and significance for native folds. Moreover, the scoring scheme has the potential to provide a reasonable balance of detail and ion such that it is also useful for the recognition of distantly related (both homologous and non-homologous) proteins. This is demonstrated here on a set of structural alignments showing much better correspondence of native and model scores for the Voronoi potentials as compared to conventional distance-based potentials. AVAILABILITY: The potentials are made available via the program system ToPLign (URL: http://cartan.gmd.de/ToPLign.html). CONTACT: Ralf.Zimmer,Ralf.Thiele@gmd.de

Algorithms↗

Lower extremity manifestations of vascular disease.

All podiatrists are required to know the anatomy and pathophysiology of vascular pathology because it is the leading cause of morbidity and mortality in the western world and a frequent complaint of podiatry patients. Podiatrists have a unique opportunity to reduce the risk of lower extremity vascular pathology, specifically PVD, by encouraging proper diet and exercise in the podiatric patient. Because the next century will bring a population explosion of older people, particular attention must be paid to the multiple and complex disorders that impair functional independence and compromise quality of life--one of the most important disorders being vascular disease. Successful treatment depends on recognition of lower extremity pathology (whether it be arterial, venous, or lymphatic) and the possible suprastructural causes and timely referrals to a vascular specialist when indicated.

Arterial Occlusive Diseases↗

[Selenium substitution in acute myocardial infarct].

BACKGROUND: Previous examinations have demonstrated decreased selenium levels in serum and full blood in patients with myocardial infarction. PATIENTS AND METHOD: 28 patients received a selenium treatment additional to the usual treatment of myocardial infarction. 19 patients with myocardial infarction with no supplementary selenium treatment served as a control group. Selenium levels in serum, full blood and urine were measured and the complications of the myocardial infarction documanted. RESULTS: There was a significant increase of serum and full blood selenium and glutathione peroxidase levels under i.v. selenium therapy in the acute phase of myocardial infarction (first to third day). Left heart failure more rarely occurred in the selenium group (20%) than in control patients (57%). Acute tachycardial cardiac rhythm disturbances such as ventricular extrasystoles and couplets diminished in both groups; ventricular extrasystoles decreased in the selenium group. CONCLUSIONS: Selen should be substituted in patients with acute myocardial infarction and decreased selen levels. It would be useful to carry out a prospective double-blind study.

Administration, Oral↗

Predominant involvement of motor fibres in patients with critical illness polyneuropathy.

Critical illness polyneuropathy (CIP) is a recognized cause of muscle weakness and failure of weaning from a ventilator. In order to characterize the features of CIP, we have examined 28 consecutive surgical patients with severe sepsis using bedside electrophysiology. Of the 28 patients (median APACHE II score 31), 20 developed moderate to severe CIP, as shown by the presence of moderate to severe denervation activity on resting EMG. The median nerve compound muscle action potential (CMAP) amplitudes were reduced to 3.24 (SEM 0.48) mV, while sensory nerve action potential (SNAP) amplitudes obtained from the same nerve were normal (13.1 (1.9) microV). In approximately 50% of these patients, the reduction in CMAP exceeded 50% of the lower limit of normal. Similar results were obtained from stimulation of the ulnar nerve. We conclude that CIP is a major complication in patients with severe sepsis and prolonged artificial ventilation. It predominantly involves motor fibres and thus markedly interferes with weaning from the ventilator.

Adolescent↗

[Experience of the intensive care physician and patient outcome].

Critically ill patients usually exhibit a wide variety of dynamic changes in various organ systems. Several outcome studies show that the presence of a trained, full-time intensivist is associated with a reduction in patient mortality. His experience leads to a decrease in otherwise frequently occurring iatrogenic complications. It thus seems beneficial to staff the intensive care unit with trained intensivists.

Clinical Competence↗

[Selenium level in patients with acute myocardial infarct and in patients with severe angina pectoris without myocardial infarct].

Selenium in serum and whole blood was determined in patients (n = 88) with acute cardiac infarction, in patients (n = 62) with severe clinical symptoms and signs of angina pectoris excluding cardiac infarction, and a control group (n = 62). The average selenium concentration of the 62 patients in the control group was 1.00 +/- 0.17 mumol/l in the blood. The serum selenium concentration of the patients with cardiac infarction was significantly decreased as compared with the control group both on the first and tenth day (alpha = 1%) as well as after three months (alpha = 5%). On the twentieth day as well as six and twelve months after cardiac infarction no significant difference could be established. At all times after cardiac infarction, the blood showed a clearly decreased selenium concentration as compared with the control group. The difference was highly significant (alpha = 0.1%) on the first, tenth and twentieth day as well as after three and six months, and it was significant (alpha = 1%) after twelve months. On the first day, the average selenium concentration in the serum of the 62 patients with a severe attack of angina pectoris excluding acute cardiac infarction was 0.88 +/- 0.18 mumol/l and thus highly significantly below the values for the control group (alpha = 0.1%). The decrease on the tenth day (0.93 +/- 0.19 mumol/l) turned out not to be significant. The blood selenium concentration was highly significantly decreased on the first and tenth day (alpha = 0.1%). It was measured to be 1.12 +/- 0.19 mumol/l and 1.10 +/- 0.20 mumol/l respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

[Selenium and antioxidant status in various diseases].

All healthy mammalian organisms are characterized by an equilibrium between the occurrence of highly reactive oxygen species and their destruction by anti-oxidants. Numerous diseases go hand in hand with a disturbance of the homoeostatis. In order to avoid or minimize the destructive effect of the oxidant stress on biological structures, therapies utilizing drugs with anti-oxidant effects are increasingly being applied. Preconditions for these therapies are a characterisation and a follow-up of the anti-oxidant status in the diseased organism. In the course of the present study selenium, glutathione peroxidase and malondialdehyde were determined in patients with various clinical pictures (terminal renal insufficiency, septic shock, high-risk gravidieties, arterioscleroisis, pulmonary carcinoma, acute myocardial infarction, test patients taking the contraceptive pill). Patients with terminal renal insufficiency and those suffering from septic shock syndromes clearly show a selenium decrease in serum and whole blood as well as a drop in the GSH-Px-activity, and increased malondialdehyde concentrations in the serum. Both are a reflection of an increased lipid peroxidation. First results of a selenium therapy are available for patients with therminal renal insufficiency and post-traumatically induced renal failure. The interpretation of the findings in the categories "high-risk gravidity" and "women on the contraceptive pill", which show a normal GSH-Px-activity and significantly increased malondialdehyde concentrations, seems problematic. The organism counteracts an increased lipid peroxidation with a normal plasma-GSH-Px-activity, clearly a sign of a still normal anti-oxidant potential.

Acute Kidney Injury↗

Recursive dynamic programming for adaptive sequence and structure alignment.

We propose a new alignment procedure that is capable of aligning protein sequences and structures in a unified manner. Recursive dynamic programming (RDP) is a hierarchical method which, on each level of the hierarchy, identifies locally optimal solutions and assembles them into partial alignments of sequences and/or structures. In contrast to classical dynamic programming, RDP can also handle alignment problems that use objective functions not obeying the principle of prefix optimality, e.g. scoring schemes derived from energy potentials of mean force. For such alignment problems, RDP aims at computing solutions that are near-optimal with respect to the involved cost function and biologically meaningful at the same time. Towards this goal, RDP maintains a dynamic balance between different factors governing alignment fitness such as evolutionary relationships and structural preferences. As in the RDP method gaps are not scored explicitly, the problematic assignment of gap cost parameters is circumvented. In order to evaluate the RDP approach we analyse whether known and accepted multiple alignments based on structural information can be reproduced with the RDP method. For this purpose, we consider the family of ferredoxins as our prime example. Our experiments show that, if properly tuned, the RDP method can outperform methods based on classical sequence alignment algorithms as well as methods that take purely structural information into account.

Amino Acid Sequence↗

[Tumor vaccination in renal cell carcinoma with and without interleukin-2 (IL-2) as adjuvant. A clinical contribution to the development of effective active specific immunization].

Interleukin 2 (IL2) production is known to bypass T-helper-cell function in the generation of an antitumour response. The present analysis was designed to assess the effects of application of renal cancer vaccine with and without IL2 on delayed-type hypersensitivity (DTH) skin responses to the vaccine itself and tumour cell challenge. The renal cancer vaccine consisted of Newcastle disease virus (NDV)-infected autologous irradiated tumour cells and topical application of low-dose rIL2 (75,000 Cetus units). As a result, the coadministration of a supplement of rIL2 proved to be important for augmentation of DTH responsiveness to tumour cell challenge. Patients with aneuploid tumours vaccinated without rIL2 developed an anergy to the vaccine throughout vaccination. This effect could be reversed by the topical coapplication of this cytokine. While the treatment of renal cancer patients with IL2-based immunotherapy regimens appears to be effective in advanced renal cell carcinoma the IL2-supplemented vaccines should be tested to assess their benefit in the situation of "minimal disease" after surgery especially in high-risk patients with aneuploid tumours.

Aneuploidy↗

[The use of a hydrolysis residue from lysine production in a straw concentrate mixture for fattening lambs].

The validity of residues from hydrolysis of soya bean meal for production of lysine was tested in a growth experiment with 2 groups of 25 cross breeding lambs as well as in a N-balance trial with 5 lambs. The animals in the growth experiment started with an average body weight of 25 kg. An industrially produced concentrate for lamb fattening was given to the animals of the control group. To the second group a straw-concentrate mixture was given, containing 30% straw, 52% barley, 5% soya bean meal, 5% dried beet pulp and 5% of hydrolysis residue. The mixture included 10.71 MJ ME resp. 5.51 MJ net-energy fat (cattle) and 166 g digestible crude protein per kg dry matter. The lambs of group 2 showed an 8% lower intake of DM, connected with a 26% intake of energy and 32% lower intake of DCP in comparison to the control group. The average daily body weight gain was 374 g for the control group and 241 g for group 2 respectively, the difference being statistically significant. The feed/gain ratio was in group 2 = 14% higher for energy and 6% higher for DCP than in the control group. The N-balance trial resulted in a N-retention of 25 percent of the N-intake. The results approved the possible use of 5% of the hydrolysis residue product for 2% crude protein in straw-concentrate mixtures for ruminants.

Animal Feed↗

Induced hypertension as an approach to treating acute cerebrovascular ischaemia: possibilities and limitations.

As, after an stroke, the autoregulation of the cerebral vessels in the ischaemic region is disturbed to a high degree, it is, on principle, possible to improve the blood flow particularly in the zone surrounding the infarct (penumbra) by raising the systemic blood pressure. During a basic treatment with low-molecular dextrans (infukoll M40), 37 patients with an acute ischaemic cerebral stroke multiply underwent elevations in blood pressure up to systolic values of about 210 to 220 mmHg. A comparison with a control group (n = 44) who were treated with low-molecular dextrans revealed no differences in lethality on the 21st day after the stroke. However, a very good acute effect in terms of a short-term improvement was remarkable a result that is noteworthy also in future.

Acute Disease↗