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Biomedical subjects

H Gohlke

Publications and source records attributed to H Gohlke.

At least 19 recordsLinked to original sources
PubMed2002

[The coronary heart disease factors obesity, faulty nutrition, smoking, inactivity. Give your patient the deciding motivation].

Primary prevention of cardiovascular disease means recognizing risk factors and--as far as possible--eliminating them. Risk factors that can be influenced include smoking, a high-fat diet and lack of exercise which, by damaging the endothelium and causing atherosclerosis, can lead to myocardial infarction and stroke. It is estimated that 70-80% of all cardiovascular events could be avoided by adopting an optimized lifestyle. The rewards of implementing a more health-conscious way of life are improved quality of life and an increase in life expectancy of five to six years. The aim of the Germany-wide "CHD Scoring Week" lasting from 3 June to 7 June, organized in cooperation with the German Cardiological Society, is to promote a greater awareness of the need for primary prevention among both physicians and patients.

Aged↗
PubMed2002

[Nutrition and body weight].

Certain dietary components play a key role for the development of coronary artery disease (CAD). Complex carbohydrates lower the prevalence of CAD. Protein should provide 15% of daily calories. Populations with a high consumption of soy protein have a low coronary event rate and a high life expectancy. Soy protein has a favorable effect on LDL cholesterol, triglycerides and HDL cholesterol. Dietary cholesterol correlates with an increased incidence of CAD. Saturated fats increase cholesterol levels as well as the activity of clotting factor VII and promote progression of CAD. Mono-(MUFA) and poly-unsaturated fatty acids lower LDL-cholesterol to a similar extent. MUFA are contained in rape seed oil, olive oil and pea nut oil, but also in avocados and almonds. Omega-3-fatty acids are in fatty fish like salmon, tuna and herring and improve survival after myocardial infarction. They improve among others endothelial function (adhesion molecules). Eating 1-2 fish meals per week has a preventive effect on CAD and stroke. Dietary fiber decreases the risk for CAD up to 30% and favorably influences carbohydrate metabolism. Antioxidants have a favorable effect in their natural form (fruits and fresh vegetables). The secondary preventive effect of a mediterranean diet after myocardial infarction (probably by a combination of the above effects) has been validated. Body weight correlates with coronary risk, diabetes and use of health care resources. A reduction of body weight is best achieved by calory reduction plus an increase of physical activity. A calory-adjusted diet, low in total fat with a significant proportion of unsaturated fats and omega-3-fatty acids and rich in fiber is of great importance for primary and secondary prevention of cardiovascular diseases. Fruits, vegetables and whole grain products are important components of this diet, which lowers the coronary event rate, increases longevity and is associated with a low rate of malignancies and osteoporosis.

Body Weight↗
PubMed2001

Fine mapping and single nucleotide polymorphism association results of candidate genes for asthma and related phenotypes.

Several genome-wide screens for asthma and related phenotypes have been published to date but data on fine-mapping are scarce. For higher resolution we performed a fine-mapping study with 2 cM average spacing in often discussed asthma candidate regions (2p, 5q, 6p, 7p, 9q, 11p, and 12q) to narrow down the regions of interest. All participants of a Caucasian family study (97 families with at least two affected sib pairs) were genotyped for 49 supplementary polymorphic dinucleotide markers. Our results indicate increased evidence for linkage on chromosome 6p, 9q, and 12q. These candidate regions were further analyzed with SNP polymorphisms in the endothelin 1 (EDN1), lymphotoxin alpha (LTA), and neuronal nitric oxide synthase (NOS1) genes. In addition, IL4 -590C>T and IL10 -592C>A, localized on chromosomes 5q and 1q, respectively, have been analyzed for SNP association. Of the six SNPs tested, four revealed weak association with the examined phenotypes. These are the IL10 -592C>A SNP in the interleukin 10 gene (p=0.036 for eosinophil cell counts), the 4124T>C SNP in EDN1 (p=0.044 for asthma), the 3391C>T SNP in NOS1 with eosinophil cell counts (p=0.0086), and the 5266C>T polymorphism, also in the NOS1 gene, for high IgE levels (p=0.022). In summary, fine mapping data enable us to confine asthma candidate regions, while variants of EDN1 and NOS1, or nearby genes, may play an important role in this context.

Asthma↗
PubMed2001

[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↗
PubMed2001

Statistical potentials and scoring functions applied to protein-ligand binding.

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.

Drug Evaluation, Preclinical↗
PubMed2001

Transport of peptidomimetic thrombin inhibitors with a 3-amidino-phenylalanine structure: permeability and efflux mechanism in monolayers of a human intestinal cell line (Caco-2).

PURPOSE: Peptidomimetic thrombin inhibitors derived from Nalpha-(2-naphthylsulfonyl)-3-amidino-phenylalanine with different basic and acidic substituents were investigated with respect to their intestinal transport behavior. METHODS: Intestinal permeability coefficients were studied using Caco-2 monolayers and a reversed-phase HPLC method for quantitation. RESULTS: Apparent permeability coefficients Papp of compounds with a free amidino group were in general low (<10 x 10(-8) cm/s) and independent of the structure of the amide part (C-terminus). Polarized efflux, however, was strongly affected by substituents in the amide moiety yielding the following efflux ratios (ER): methylpiperidide (1) (ER 45) > piperidine carboxylic acid methylester (ER 6-11) > piperidine carboxylic acids (ER 1.9-2.9) > piperazide (ER -0.17). Efflux of (1) was temperature-dependent, but independent of the enantiomeric configuration, accompanied by an increase in transepithelial electrical resistance (TEER), and could be reduced by P-gp inhibitors (PSC 833, Cremophor EL) but not by indomethacin. Replacement of the amidine group of (1) by aminomethyl-, amino-, and oxamidine- moieties drastically increased absorptive permeability (46-68 fold) with ER < 3.4. In contrast, the oxamidine with a C-terminal nipecotic acid residue (8) displayed also a temperature dependent efflux- without altering TEER (ER 22). This efflux was sensitive to PSC833/Cremophor EL and indomethacin. CONCLUSIONS: Basic and acidic residues of amidino-phenylalanine-derived thrombin inhibitors mediate affinity to intestinal efflux pumps. presumably P-gp and MRP. P-gp mediated efflux was related to a net positive charge and accompanied by an increased TEER. Among the methylpiperide (1) promoieties studied the oxamidino group seems to be very promising in overcoming both transport and efflux problems frequently encountered with peptidomimetics containing amidines.

Amidines↗
PubMed2001

Cardiac risk factors, medication, and recurrent clinical events after acute coronary disease; a prospective cohort study.

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.

Aged↗
PubMed2000

[Secondary prevention in coronary patients after inpation rehabilitation].

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.

Aftercare↗
PubMed2000

[Effect of optimized integrated management on long-term effectiveness of cardiologic rehabilitation].

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.

Aged↗
PubMed2000

Knowledge-based scoring function to predict protein-ligand interactions.

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.

Artificial Intelligence↗
PubMed1999

[Effects of inpatient rehabilitation on cardiovascular risk factors in patients with coronary heart disease. PIN-Study Group].

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.

Aftercare↗
PubMed1999

[Evidence-based medicine in cardiology with an example of secondary prevention of coronary heart disease].

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.

Coronary Disease↗
PubMed1998

Cardiac rehabilitation.

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.

Combined Modality Therapy↗
PubMed1998

Cardiac rehabilitation: where are we going?

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.

Cholesterol↗