Biomedical subjects
Publications and source records attributed to H Gohlke.
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In virtual screening, small-molecule ligands are docked into protein binding sites and their binding affinity is predicted. Knowledge-based, regression-based and first-principle-based methods have been developed to rank computer-generated binding modes. As a result of still existing deficiencies, a best compromise might be the combination of several scoring schemes into a consensus scoring approach.
AIMS: Systematic data are sparse on clinical outcome after acute coronary disease followed by cardiac rehabilitation therapy. Therefore, our objective was to determine the long-term development of cardiac risk factors, recurrent clinical events, and cardiac medication in patients undergoing routine in hospital cardiac rehabilitation therapy. METHODS AND RESULTS: In the prospective PIN Study (Post Infarct Care), 2441 consecutive patients (78% men, 60+/-10 years, 22% women, 65+/-10 years) were enrolled in 18 inpatient rehabilitation centres in Germany following myocardial infarction (56%), coronary artery bypass graft (38%) or percutaneous transluminal coronary angioplasty (6%). Cardiac risk factors, pre-specified clinical end-points, and the prescription of cardiac medication were prospectively documented on admission to and at discharge from rehabilitation therapy, and 3, 6 and 12 months later by obtaining information with standardized questionnaires from the patients and their physicians. The cardiac risk factors improved initially during cardiac rehabilitation therapy, but deteriorated within the following 12 months: 39% patients smoked at the beginning vs 5% at the end of in hospital rehabilitation vs 10% at 12 months follow-up (P<0.001). The respective numbers for patients with blood pressure >140 and/or 90 mmHg were 24 vs 8 vs 25% (P<0.01) and with plasma cholesterol >200 mg. dl(-1)57 vs 29 vs 51% (P<0.01). A total of 886 patients experienced one or more recurrent clinical events during the first year, 69% of those within the initial 6 months. At 12 months follow-up, 77% of patients received aspirin, 70% beta-blockers, 62% lipid lowering medication, and 53% angiotensin converting enzyme inhibitors. CONCLUSION: The present results indicate that the benefit of cardiac rehabilitation therapy following acute coronary events is only partially maintained during the following year. Continuous strategies of medical care need to be developed to improve the long-term outcome in coronary patients.
BACKGROUND AND OBJECTIVE: [corrected] Data on impressive improvements in the prognosis and clinical progress of patients with coronary heart disease (CHD) through consistent reduction of risk factors and administration of cardioprotective drugs have led to the formulation of guidelines by professional associations. The aim of this prospective, multicenter cohort study (PIN: Post-Infarkt-Nachsorge = Postinfarction Aftercare) was to determine the extent to which these recommendations are implemented in the long term in patients who have had an acute coronary event and are undergoing rehabilitation therapy. PATIENTS AND METHODS: From January to May 1997, 2441 patients at 18 rehabilitation centers (22% women, 65 +/- 10 years; 78% men, 60 +/- 10 years) with diagnosed CHD following an acute cardiac event were enrolled in the study. Risk factors and pharmacologic therapy were recorded by the patients' GPs on a standardized questionnaire on admission to and discharge from rehabilitation therapy (RT) as well as after 3, 6, and 12 months. New clinical events were documented by questioning the patients and their attending physicians. RESULTS: After an impressive reduction of cardiovascular risk factors during RT, the percentage of patients with blood pressure values > 140/90 mmHg rose from 8% to 25% after 12 months (p < 0.001). 11% vs 17% of the patients had glucose levels > 140 mg/dl and 29% vs 51% had total cholesterol levels > 200 mg/dl (p < 0.001). 5% of the patients smoked at the time of discharge, 10% after one year. Compared to the time of discharge, significantly fewer beta-receptorblockers, lipid-lowering drugs, angiotensin converting-enzyme (ACE) inhibitors, and acetylsalicylic acid were prescribed. During follow-up observation, 886 patients suffered one or more clinical events, of which 69% occurred in the first six months. CONCLUSION: The interventional success of in-patient rehabilitation therapy is not sustained in the long term. This could be due to deficient implementation of guidelines for the secondary prevention of CHD, as the cardiovascular risk factors exceed pathological limits in a large proportion of patients and the prescription of cardioprotective medications is less than optimal.
BACKGROUND AND OBJECTIVE: Long-term risk factor (RF) modification after cardiac rehabilitation (CR) is less than satisfactory. Problems of communication between the CR centre and the practising physician (GP) are one potential source of sub-optimal management. The goal of the PROTECT-study was to evaluate the influence of improved communication between rehabilitation centres and the GP on the quality of RF-modification. PATIENTS AND METHODS: In 50 specialized CR centres 882 patients in the group with intensified communication were compared to 160 patients in the usual care group. All patients underwent a course of residential CR. Intensified communication was attempted by a total of four phone calls to the GP, a RF booklet in which the RF profile, the individual RF treatment goals and the current RF status were delineated. Main treatment goals with respect to RF-modification after 6 months were: Blood pressure < 140/90 mmHg, LDL-Cholesterol < 100 mg/dl or at least 115 mg/dl and a body mass index of < 25 or at least < 30. RESULTS: The percentage of of patients with adequate blood pressure control (< 140/90 mmHg) was 85.1% vs. 85%, with LDL-cholesterol < 100 mg/dl 27.2% vs. 23.9%, with good body-mass index (< 25) 32.4% vs. 28.2% (intensified communication vs. control group; p = ns). The treatment initiated by the CR centres was continued in about 90% of patients. CONCLUSION: The study has shown that improved communication between the CR centres and the GP's after CR had only a marginal effect on the quality of RF-management. One key element of secondary prevention could be to get the patient more strongly involved in reaching the targets of therapy.
The development and validation of a new knowledge-based scoring function (DrugScore) to describe the binding geometry of ligands in proteins is presented. It discriminates efficiently between well-docked ligand binding modes (root-mean-square deviation <2.0 A with respect to a crystallographically determined reference complex) and those largely deviating from the native structure, e.g. generated by computer docking programs. Structural information is extracted from crystallographically determined protein-ligand complexes using ReLiBase and converted into distance-dependent pair-preferences and solvent-accessible surface (SAS) dependent singlet preferences for protein and ligand atoms. Definition of an appropriate reference state and accounting for inaccuracies inherently present in experimental data is required to achieve good predictive power. The sum of the pair preferences and the singlet preferences is calculated based on the 3D structure of protein-ligand binding modes generated by docking tools. For two test sets of 91 and 68 protein-ligand complexes, taken from the Protein Data Bank (PDB), the calculated score recognizes poses generated by FlexX deviating <2 A from the crystal structure on rank 1 in three quarters of all possible cases. Compared to FlexX, this is a substantial improvement. For ligand geometries generated by DOCK, DrugScore is superior to the "chemical scoring" implemented into this tool, while comparable results are obtained using the "energy scoring" in DOCK. None of the presently known scoring functions achieves comparable power to extract binding modes in agreement with experiment. It is fast to compute, regards implicitly solvation and entropy contributions and produces correctly the geometry of directional interactions. Small deviations in the 3D structure are tolerated and, since only contacts to non-hydrogen atoms are regarded, it is independent from assumptions of protonation states.
BACKGROUND AND OBJECTIVE: The prognostically favourable effect of secondary prevention in patients with proven coronary heart disease (CHD: documented myocardial infarction, angiographically proven coronary artery stenosis > 60% and/[or] status after coronary artery surgery) has been demonstrated. But it has not been adequately shown to what extent the guidelines laid down by specialist societies is being followed in routine clinical practice. Nor have there been any large-size standardized investigations of whether in-hospital rehabilitation decreases cardiovascular risk factors. It was the aim of this study to investigate the acute effects on cardiovascular risk factors of in-hospital post-infarction rehabilitation. PATIENTS AND METHODS: From January to May 1997, at 18 rehabilitation clinics, 2441 consecutive patients (22% women, aged 65 +/- 10 years, 78% men, aged 60 +/- 10 years) with proven CHD were included in this post-infarction after-care (PIN) study. During their hospital stay (26 +/- 5 days) they undertook physical training appropriate for cardiological follow-up treatment, as well as various other modes of treatment to affect risk factors. Diagnosis, treatment and standardized data were prospectively recorded on admission and discharge. RESULTS: At discharge the proportions of patients with conventionally defined risk factors were significantly lower than on admission (P < 0.001). The proportion was 8% in patients with arterial blood pressure > 140/90 mm Hg (vs. 24% on admission), 5% in smokers (vs. 39% on admission), 30% vs. 60% in patients with cholesterol levels > 200 mg/dl, 67% vs. 87% in those with low density lipids > 100 mg/dl, 15% vs. 22%, in those with serum triglyceride levels > 200 mg/dl, 11% vs. 14% in those with glucose levels > 140 mg/dl, and 15% vs. 18% in patient with a body/mass index > 30 kg/m2. There was an increase in the proportion of patients who during their hospital stay were prescribed additional drugs: from 85% to 86% for acetylsalicylic acid (P < 0.05), 61% to 77% for beta-adrenergic receptor blockers, 33% to 67% for cholesterol synthesis enzyme (CSE) inhibitors, and 51% to 57% for angiotensin converting enzyme (ACE) inhibitors. CONCLUSION: Modifiable cardiovascular risk factors can be reduced by various methods of rehabilitation and more intensive drug treatment during hospitalization. By taking account of evidence-based medicine favourable conditions can be created for longterm ambulant after-care.
The fear that application of EBM could lead to a cook-book type medicine has not been substantiated. The challenge is to evaluate and treat the individual patient according to his/her particular situation. The goal of secondary prevention is the reduction of the global risk. As patients with coronary artery diseases have a high event rate (> 20% in 10 years), intensive measures with proven benefit for risk reduction should be undertaken. Guidelines of national or European societies are helpful for the daily routine. However, the application of these guidelines is less widely used than expected which leads to less than optimal treatment. This is a universal phenomenon. The reasons may differ in different countries. Financial problems may be one limiting factor. However, the overal costeffectiveness of these measures for the social system is usually not taken into account. Educational efforts directed to patients, physicians and health care providers will be necessary to overcome this problem.
Cardiac rehabilitation as a multifactorial intervention has been shown to improve functional capacity, emotional well-being, return to work rate and longevity. Cardiac rehabilitation is cost effective, and in many aspects represents causal therapy. The meta-analyses do not include studies where pharmacological lipid lowering was used. The use of generally accepted and recommended medical treatment strategies in the EuroAspire study has been below the expected rate, Therefore, cardiac rehabilitation programmes should educate the patient and emphasize the need to apply the appropriate medical regimen in addition to the non-pharmacological treatment modalities of cardiac rehabilitation to achieve maximal benefit. Cardiac rehabilitation has an important role in assuring the application of the available knowledge, to avoid cardiac complications and progression of disease, and improve cardiorespiratory fitness and survival. Cardiac rehabilitation should therefore be an integral part of cardiological management after a cardiac event.
Several components of cardiac rehabilitation can be considered to be of proven value: smoking cessation reduces cardiac events by 50% in observational studies, dietary modification such as the so-called Mediterranean diet--if rigorously applied--reduces cardiac events, decreases progression and has favourable effects on hypertension, osteoporosis and the risk of cancer. Cholesterol lowering by HMG-CoA reductase inhibitors is cost effective but not practiced widely enough. Exercise training programmes improve functional capacity and symptoms particularly in patients with compensated heart failure. The prognostic implications are unclear at present. Stress modification is useful and return to work may be enhanced by cardiac rehabilitation. Cardiac rehabilitation, as a multifactorial intervention prevents progression, improves well being and prognosis, and should be an integral part of the cardiological management after a cardiac event.
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Endurance training after myocardial infarction results in increased fitness and favours regression of coronary arteriosclerosis if the intensity of the training programme results in an expenditure of at least 2200 Kcalories per week. During physical exercise the risk of sudden death is increased, however the net effect of endurance training results in a decreased risk of sudden cardiac death and also of reinfarction. Very intense physical activity may trigger a myocardial infarction and should be avoided by patients with coronary artery disease. Patients with uncomplicated myocardial infarction benefit from a structured exercise programme lasting 6 months or longer. After a large anterior myocardial infarction moderate physical activity does not have an apparent effect on left ventricular size or remodelling. In patients with a low ejection fraction and borderline compensation, physical activity should be delayed until a better degree of cardiac compensation is achieved. The intensity of exercise most be closely supervised to avoid cardiac decompensation. Regular physical activity is an important component of secondary preventive measures in virtually all patients with established coronary artery disease.
The prevalence of silent, previously undiagnosed, exercise-induced ischemia is between 0.5 und 3.5% in 40-59-year-old men. Its prevalence is dependent upon the prevalence of coronary artery disease in the population or sub-population considered. The pathophysiological mechanism of silent ischemia is extracardiac. The prognosis of silent ischemia is determined by the functional impairement and the extent of coronary artery disease. The decision concerning medical and surgical treatment of patients with silent ischemia is based on the same criteria as in patients with ischemia and angina pectoris: patients at high risk (ischemia at low levels of exercise, marked exercise-induced ischemia, proximal 3-vessel disease and at least moderately impaired left ventricular function) are candidates for invasive treatment. Patients with ischemia at high levels of exercise, or with minimal ischemia with one- or two-vessel disease, are candidates for medical management. The best possible control of all cardiovascular risk factors is mandatory for all patients, from the viewpoint of prognosis in particular.
The efficacy of the heparin-induced extracorporeal LDL-precipitation (HELP)-apheresis procedure has been studied in an open prospective multicentre trial. After 2 years of regular weekly HELP-treatment the data from 39 of 51 patients could be evaluated according to the study criteria. Twelve of the initially recruited study patients were omitted from the evaluation either because of premature termination of the treatment or because they did not fulfil the exact guidelines of the study protocol. A mean of 2.831 plasma was regularly treated on average every 7.85 days. The mean pre-/post-apheresis LDL-cholesterol levels decreased from 286/121 mg dl-1 at the first HELP treatment to 203/77 mg dl-1 after 1 year and to 205/77 mg dl-1 after 2 years of regular apheresis; the corresponding values for fibrinogen were 314/144, 246/98 and 250/105 mg dl-1, respectively. In contrast, the mean pre-/post-apheresis HDL-cholesterol levels rose from 41/38 through 51/44 mg dl-1 after 1 year to 52/43 mg dl-1 after 2 years of treatment. The overall result was a normalization of the atherogenic index (LDL-/HDL-cholesterol ratio) from 6.9/3.2 to 4.0/1.9. The angiographies from 33 patients obtained before and after 2 years of regular treatment could be evaluated blindly using the cardiovascular angiography analysis system. The mean degree of stenosis of all segments decreased from 32.5% (SD = 16) to 30.6% (SD = 16.8) over the 2 years. A regression > 8% was observed in 50/187 (26.7%) segments, whereas 29/187 (15.5%) segments showed progression. In 108/187 (57.8%) segments the lesions were stable (< 8% deviation) over 2 years. We conclude that regular treatment with HELP-LDL-apheresis is able to stabilize progressive atherosclerotic disease and to induce almost twice as much regression as progression of atherosclerotic lesions.
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Between 1978 and 1987, 1270 patients who survived single aortic or mitral valve replacement at the Rehabilitation Center in Bad Krozingen, Germany, underwent a comprehensive rehabilitation program. The preoperative diagnosis was isolated aortic stenosis in 425, isolated aortic regurgitation in 159, mixed aortic lesion in 211, isolated mitral stenosis in 208, isolated mitral insufficiency in 137 and mixed mitral lesion in 130 cases. Follow up examinations were carried out one and six months after surgery, and at yearly intervals thereafter. Exercise testing was performed with an electrically braked bicycle ergometer in the supine position, and the load was increased by 25 or 50 watts every two minutes until fatigue, severe angina, more than 0.3 mV ST-segment depression, or 80% of the age predicted maximum heart rate was achieved. Patients after aortic valve replacement had a better exercise performance one month after operation than did those after mitral valve replacement. Those with mitral stenosis showed more severe impairment of exercise tolerance than did the mitral insufficiency group. There was a steady increase in exercise tolerance between one and six months postoperatively, both in patients with aortic and those with mitral valve replacement, but the difference in performance between the two groups was still present (72% versus 57% of normal). The results of univariate and multivariate analyses showed that the preoperative employment status was the most important factor for postoperative return to work, followed by gender (male > female), exercise tolerance and valualar lesion (aortic > mitral).(ABSTRACT TRUNCATED AT 250 WORDS)
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The importance of hypercholesterolemia for the development of atherosclerotic lesions is undebatable. It is less evident, however, whether the progression of established lesions can be influenced by modifying lipid levels. The review of seven controlled angiographic intervention trials shows that different criteria are used to define progression of lesions. The relation of progression to regression (progression/regression ratio), however, is a useful marker for the activity of coronary artery disease. Patients with familial hypercholesterolemia have a progression/regression ratio of between 3 and 7. There is a consistent relationship between the progression/regression ratio and the LDL-/HDL-cholesterol ratio in both control and intervention groups in these trials. Groups with a LDL-/HDL-cholesterol ratio of 5 have six times more progression than regression. If the LDL-/HDL-cholesterol ratio is less than 2.5 regression occurs more often than progression (i.e. progression/regression ratio less than 1). Thus, in the management of hyperlipidemic patients a LDL-/HDL-cholesterol ratio of less than 2.5 should be achieved if regression of atherosclerotic lesions is desired.