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Biomedical subjects

R Dietz

Publications and source records attributed to R Dietz.

At least 37 records · Page 2Linked to original sources
PubMed2004

Reference values for cardiac troponins I and T in a goal-oriented concept of health: cardiac marker values in a series of outpatients without acute coronary syndromes.

BACKGROUND: Cardiac troponins are part of the new definition of acute myocardial infarction (AMI) by the European Society of Cardiology and the American College of Cardiology (ESC/ACC). In the new guidelines, it was suggested to establish reference values for cardiac troponins to calculate the 0.99 quantile (Q99) as cutoff for AMI diagnosis. PATIENTS AND METHODS: We run a prospective series of troponin measurements in unselected outpatients who had no suspicion of cardiac ischemia. The selection of patients as reference population is based on a "goal-oriented concept of health". One hundred and ninety-five patients agreed that 10-ml additional blood was drawn at the occasion of the venous puncture done routinely in the evaluation of their case. Cardiac troponin I was measured using a point of care (POCT) device (Stratus CS, DadeBehring, TNI-PO). Additionally, heparin-plasma was obtained and immediately deep-frozen to -80 degrees C for later batch measurement of cardiac troponin T (Elecsys 2010, Roche Diagnostics, TnT) and troponin I (Centaur, Bayer, TnI-CL). RESULTS: The Q99 values were 0.14 microg/l for TnI-PO, 0.023 microg/l for TnT and 0.07 microg/l for TnI-CL in patients with creatinine levels below 1.5 mg/dl. These values lay above those obtained from people at good health for reference study purposes. On the level of our cutoffs, CVs were 7.5%, 6.4% and 23.7% for TnI-PO, TnT and TnI-CL, respectively. CONCLUSIONS: Only the TnI-PO and TnT tests fulfilled the imprecision criteria in our study. TnI-PO values between 0.10 and 0.14 microg/l and TnT values between 0.01 and 0.03 microg/l have to be interpreted carefully. Patients presenting with chest pain will be possibly true positives, but patients without chest pain and nondiagnostic ECGs should be subjected to repetitive troponin measurements and further noninvasive investigation and maybe not directly sent to the cardiac catheter laboratory.

Adult↗
PubMed2003

[Atypical Leriche syndrome].

A 73-year old woman presented with mild paraparesis and hypesthesia of the legs. Furthermore, she complained dizziness, fainting and dyspnea. There was a history of peripheral artery disease, diabetes mellitus, arterial hypertension and chronic atrial fibrillation. Five years ago she had breast cancer with removal of the left mamma and additional radiation therapy. Cardiac catheterization at that time demonstrated no significant coronary stenoses. A contrast-enhanced CT-scan excluded lumbal spinal metastases. Instead, a subtotal occlusion of the abdominal aorta was noticed, but was initially interpreted as a chronic thrombosis because there were no typical symptoms and only moderate pain. About 24 hours later the patient developed an acute ischemic syndrome of the legs with progressive paraparesis, cold and pale legs in combination with acidosis and hyperventilation. Color-coded duplex ultrasound showed only a small turbulent flow in the ilial arteries, highly suspicious of a complete occlusion of the distal aorta. Angiography revealed an acute total occlusion of the infrarenal aorta without collaterals. During surgical intervention, complete obstruction of the abdominal aorta above the bifurcation was confirmed. Subsequent embolectomy was performed and an embolus consisting of several layers of different age was extracted. After successful surgical intervention with subsequent clinical improvement, the patient's clinical condition deteriorated a few day later. She died on day 9 after surgery from a complete ischemia of the small intestine and the colon ascendens.

Aged↗
PubMed2003

The EuroHeart Failure Survey programme--a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment.

BACKGROUND: National surveys suggest that treatment of heart failure in daily practice differs from guidelines and is characterized by underuse of recommended medications. Accordingly, the Euro Heart Failure Survey was conducted to ascertain how patients hospitalized for heart failure are managed in Europe and if national variations occur in the treatment of this condition. METHODS: The survey screened discharge summaries of 11304 patients over a 6-week period in 115 hospitals from 24 countries belonging to the ESC to study their medical treatment. RESULTS: Diuretics (mainly loop diuretics) were prescribed in 86.9% followed by ACE inhibitors (61.8%), beta-blockers (36.9%), cardiac glycosides (35.7%), nitrates (32.1%), calcium channel blockers (21.2%) and spironolactone (20.5%). 44.6% of the population used four or more different drugs. Only 17.2% were under the combination of diuretic, ACE inhibitors and beta-blockers. Important local variations were found in the rate of prescription of ACE inhibitors and particularly beta-blockers. Daily dosage of ACE inhibitors and particularly of beta-blockers was on average below the recommended target dose. Modelling-analysis of the prescription of treatments indicated that the aetiology of heart failure, age, co-morbid factors and type of hospital ward influenced the rate of prescription. Age <70 years, male gender and ischaemic aetiology were associated with an increased odds ratio for receiving an ACE inhibitor. Prescription of ACE inhibitors was also greater in diabetic patients and in patients with low ejection fraction (<40%) and lower in patients with renal dysfunction. The odds ratio for receiving a beta-blocker was reduced in patients >70 years, in patients with respiratory disease and increased in cardiology wards, in ischaemic heart failure and in male subjects. Prescription of cardiac glycosides was significantly increased in patients with supraventricular tachycardia/atrial fibrillation. Finally, the rate of prescription of antithrombotic agents was increased in the presence of supraventricular arrhythmia, ischaemic heart disease, male subjects but was decreased in patients over 70. CONCLUSION: Our results suggest that the prescription of recommended medications including ACE inhibitors and beta-blockers remains limited and that the daily dosage remains low, particularly for beta-blockers. The survey also identifies several important factors including age, gender, type of hospital ward, co morbid factors which influence the prescription of heart failure medication at discharge.

Adrenergic beta-Antagonists↗
PubMed2003

The EuroHeart Failure survey programme-- a survey on the quality of care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis.

BACKGROUND: The European Society of Cardiology (ESC) has published guidelines for the investigation of patients with suspected heart failure and, if the diagnosis is proven, their subsequent management. Hospitalisation provides a key point of care at which time diagnosis and treatment may be refined to improve outcome for a group of patients with a high morbidity and mortality. However, little international data exists to describe the features and management of such patients. Accordingly, the EuroHeart Failure survey was conducted to ascertain if appropriate tests were being performed with which to confirm or refute a diagnosis of heart failure and how this influenced subsequent management. METHODS: The survey screened consecutive deaths and discharges during 2000-2001 predominantly from medical wards over a 6-week period in 115 hospitals from 24 countries belonging to the ESC, to identify patients with known or suspected heart failure. RESULTS: A total of 46788 deaths and discharges were screened from which 11327 (24%) patients were enrolled with suspected or confirmed heart failure. Forty-seven percent of those enrolled were women. Fifty-one percent of women and 30% of men were aged >75 years. Eighty-three percent of patients had a diagnosis of heart failure made on or prior to the index admission. Heart failure was the principal reason for admission in 40%. The great majority of patients (>90%) had had an ECG, chest X-ray, haemoglobin and electrolytes measured as recommended in ESC guidelines, but only 66% had ever had an echocardiogram. Left ventricular ejection fraction had been measured in 57% of men and 41% of women, usually by echocardiography (84%) and was <40% in 51% of men but only in 28% of women. Forty-five percent of women and 22% of men were reported to have normal left ventricular systolic function by qualitative echocardiographic assessment. A substantial proportion of patients had alternative explanations for heart failure other than left ventricular systolic or diastolic dysfunction, including valve disease. Within 12 weeks of discharge, 24% of patients had been readmitted. A total of 1408 of 10434 (13.5%) patients died between admission and 12 weeks follow-up. CONCLUSIONS: Known or suspected heart failure comprises a large proportion of admissions to medical wards and such patients are at high risk of early readmission and death. Many of the basic investigations recommended by the ESC were usually carried out, although it is not clear whether this was by design or part of a general routine for all patients being admitted regardless of diagnosis. The investigation most specific for patients with suspected heart failure (echocardiography) was performed less frequently, suggesting that the diagnosis of heart failure is still relatively neglected. Most men but a minority of women who underwent investigation of cardiac function had evidence of moderate or severe left ventricular dysfunction, the main target of current advances in the treatment of heart failure. Considerable diagnostic uncertainty remains for many patients with suspected heart failure, even after echocardiography, which must be resolved in order to target existing and new therapies and services effectively.

Aged↗
PubMed2003

Levels and patterns of persistent organochlorines in minke whale (Balaenoptera acutorostrata) stocks from the North Atlantic and European Arctic.

Regional variation in PCBs and organochlorine (OC) pesticide concentrations was examined using the blubber of 155 minke whales (Balaenoptera acutorostrata) sampled in seven regions in the North Atlantic and European Arctic, including western and southeastern Greenland, the Norwegian Sea, the North Sea and the Barents Sea. The levels and relative proportions of OCs were also used to examine the boundaries for North Atlantic minke whale stocks previously defined by the International Whaling Commission (IWC). Concentrations of major OC groups (sigmaPCB, 89.1-22 800 ng/g lipid; sigmaDDT, 65.3-6280 ng/g lipid; sigmaCHL, 33.3-2110 ng/g lipid) generally increased from west to east, while HCH concentrations (sigmaHCH, < 1-497 ng/g lipid) showed the opposite trend. Statistical comparison between six regions using sex-adjusted least squared mean concentrations showed that minke whales from the Barents Sea had significantly higher concentrations of EPCBs than those from the Vestfjorden/Lofoten, the North Sea, and west Svalbard, as well as significantly higher sigmaDDT concentrations compared to west Greenland animals. The differences in concentrations suggest that west and southeast Greenland minkes may represent one group of whales, which are distinct from both the Jan Mayen minkes and those from other IWC defined stocks in northern European waters. Principal components analysis using proportions of 71 PCB congeners and 20 OC pesticides (of total OCs) did not reveal any major differences among groups although minkes from the North Sea were distinguished from those from Greenland waters by higher loadings of more highly chlorinated PCBs and recalcitrant OC pesticides. The general similarity in mean levels of sigmaPCBs, sigmaDDT and sigmaCHL, as well as mean principal components analysis scores, among minkes sampled at Jan Mayen, Svalbard, Vestfjorden/Lofoten, the North Sea and the Barents Sea suggests that the whales are quite mobile and may feed in multiple areas within the northeastern Atlantic.

Analysis of Variance↗
PubMed2002

Management of heart failure in primary care (the IMPROVEMENT of Heart Failure Programme): an international survey.

BACKGROUND: Heart failure is a prevalent condition that is generally treated in primary care. The aim of this study was to assess how primary-care physicians think that heart failure should be managed, how they implement their knowledge, and whether differences exist in practice between countries. METHODS: The survey was undertaken in 15 countries that had membership of the European Society of Cardiology (ESC) between Sept 1, 1999, and May 31, 2000. Primary-care physicians' knowledge and perceptions about the management of heart failure were assessed with a perception survey and how a representative sample of patients was managed with an actual practice survey. FINDINGS: 1363 physicians provided data for 11062 patients, of whom 54% were older than 70 years and 45% were women. 82% of patients had had an echocardiogram but only 51% of these showed left ventricular systolic dysfunction. Ischaemic heart disease, hypertension, diabetes mellitus, atrial fibrillation, and major valve disease were all common. Physicians gave roughly equal priority to improvement of symptoms and prognosis. Most were aware of the benefits of ACE inhibitors and beta blockers. 60% of patients were prescribed ACE inhibitors, 34% beta blockers but only 20% received these drugs in combination. Doses given were about 50% of targets suggested in the ESC guidelines. If systolic dysfunction was documented, ACE inhibitors were more likely and beta blockers less likely to be prescribed than when there was no evidence of systolic dysfunction. INTERPRETATION: Results from this survey suggest that most patients with heart failure are appropriately investigated, although this finding might be as a result of high rates of hospital admissions. However, treatment seems to be less than optimum, and there are substantial variations in practice between countries. The inconsistencies between physicians' knowledge and the treatment that they deliver suggests that improved organisation of care for heart failure is required.

Aged↗
PubMed2002

Cadmium toxicity to ringed seals (Phoca hispida): an epidemiological study of possible cadmium-induced nephropathy and osteodystrophy in ringed seals (Phoca hispida) from Qaanaaq in Northwest Greenland.

The Greenland marine food chains contain high levels of cadmium, mercury and selenium. Concentrations of cadmium in the kidney of ringed seals (Phoca hispida) from the municipalities of Qaanaaq and Upernavik (Northwest Greenland) are among the highest recorded in the Arctic. The purpose of the study was to determine whether cadmium-induced damage in the kidneys and the skeletal system could be detected among 100 ringed seals from Northwest Greenland. The cadmium concentrations in the kidney cortex ranged from 0 to 248 microg/g wet weight (mean=44.5, N=100) in the 99 kidneys examined. Experience from cadmium-poisoned humans and laboratory mammals indicates that concentrations above 50-200 microg/g wet wt. may induce histopathological changes. Overall, 31 of the ringed seals had cadmium concentrations in the kidney cortex above 50 microg/g wet wt., 11 had concentrations above 100 and one had a concentration above 200 microg/g wet wt. Obvious histopathological changes (categorised mainly as glomerulonephritis) were found in 10 of the seals; however, none of these changes could be attributed to cadmium-induced renal damage (mainly tubulopathy) as described for other species. Damage to the proximal kidney tubules is known to induce demineralisation of the skeletal system (Fanconi's syndrome). Therefore, the three lowest lumbar vertebrae were scanned in 91 seals to measure the content of calcium. The 10 cases of nephropathy could neither be linked to the degree of mineralisation of the skeleton nor to the cadmium concentrations. Furthermore, the degree of mineralisation of the skeleton was not correlated with the cadmium concentration, age or sex. It can therefore be concluded that despite high levels of cadmium, none of the ringed seals showed any signs of cadmium-induced nephropathy or osteodystrophy. This might be explained by the composition of the ringed seals diet, which contains high levels of vitamin D, calcium, phosphorus, zinc, selenium and protein. These elements are all likely to counteract cadmium-induced damage. It is speculated that ringed seal are not particularly vulnerable to osteodystrophy, due to their continuous growth (bone mineralisation) throughout life and the oestrogen hormonal activity of females throughout life.

Animals↗
PubMed2002

Intracellular superoxide induces apoptosis in VSMCs: role of mitochondrial membrane potential, cytochrome C and caspases.

Apoptosis of vascular smooth muscle cells (VSMCs) is an integral part of cardiovascular diseases including atherosclerosis, hypertension and restenosis. Here we studied the fate of VSMCs in response to intracellular superoxide stimulation. Diethyldithiocarbamic acid (DDC) was used to inhibit copper-zinc superoxide dismutase thereby increasing intracellular superoxide levels. The results show that DDC at a dose from 25-100 micro M is able to induce VSMC apoptosis. Superoxide was found to be responsible for DDC-induced apoptosis. In the apoptotic process mitochondrial membrane potential was decreased and caspase-3, -8 and -9 were activated. Surprisingly, neither cytochrome c release nor Bid cleavage could be observed. These data suggest a role for intracellular superoxide in the regulation of VSMCs apoptosis.

Animals↗
PubMed2001

In cardiomyocyte hypoxia, insulin-like growth factor-I-induced antiapoptotic signaling requires phosphatidylinositol-3-OH-kinase-dependent and mitogen-activated protein kinase-dependent activation of the transcription factor cAMP response element-binding protein.

BACKGROUND: A variety of pathologic stimuli lead to apoptosis of cardiomyocytes. Survival factors like insulin-like growth factor-I (IGF-I) exert anti-apoptotic effects in the heart. Yet the underlying signaling pathways are poorly understood. METHODS AND RESULTS: In a model of hypoxia-induced apoptosis of cultured neonatal cardiomyocytes, IGF-I prevented cell death in a dose-dependent manner. Antiapoptotic signals induced by IGF-I are mediated by more than one signaling pathway, because pharmacological inhibition of the phosphatidylinositol-3-OH-kinase (PI3K) or the mitogen-activated protein kinase kinase (MEK1) signaling pathway both antagonize the protective effect of IGF-I in an additive manner. IGF-I-stimulation was followed by a PI3K-dependent phosphorylation of AKT and BAD and an MEK1-dependent phosphorylation of extracellular signal-regulated kinase (ERK) 1 and ERK2. IGF-I also induced phosphorylation of cAMP response element-binding protein (CREB) in a PI3K- and MEK1-dependent manner. Ectopic overexpression of a dominant-negative mutant of CREB abolished the antiapoptotic effect of IGF-I. Protein levels of the antiapoptotic factor bcl-2 increased after longer periods of IGF-I-stimulation, which could be reversed by pharmacological inhibition of PI3K as well as MEK1 and also by overexpression of dominant-negative CREB. CONCLUSIONS: In summary, our data demonstrate that in cardiomyocytes, the antiapoptotic effect of IGF-I requires both PI3K- and MEK1-dependent pathways leading to the activation of the transcription factor CREB, which then induces the expression of the antiapoptotic factor bcl-2.

Animals↗
PubMed2001

Amelioration of angiotensin II-induced cardiac injury by a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor.

BACKGROUND: 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have effects that extend beyond cholesterol reduction. We used an angiotensin (Ang) II-dependent model to test the hypothesis that cerivastatin ameliorates cardiac injury. METHODS AND RESULTS: We treated rats transgenic for human renin and angiotensinogen (dTGR) chronically from weeks 4 to 7 with cerivastatin (0.5 mg/kg by gavage). We used immunohistochemistry, electrophoretic mobility shift assays, and reverse transcription-polymerase chain reaction techniques. Compared with control dTGR, dTGR treated with cerivastatin had reduced mortality, blood pressure, cardiac hypertrophy, macrophage infiltration, and collagen I, laminin, and fibronectin deposition. Basic fibroblast growth factor mRNA and protein expression were markedly reduced, as was interleukin-6 expression. The transcription factors NF-kappaB and AP-1 were substantially less activated, although plasma cholesterol was not decreased. CONCLUSIONS: These results suggest that statins ameliorate Ang II-induced hypertension, cardiac hypertrophy, fibrosis, and remodeling independently of cholesterol reduction. Although the clinical significance remains uncertain, the results suggest that statins interfere with Ang II-induced signaling and transcription factor activation, thereby ameliorating end-organ damage.

Angiotensin II↗
PubMed2001

Measurement of left ventricular dimensions and function in patients with dilated cardiomyopathy.

Studies on medical therapy in heart failure are focused on changes of left ventricular (LV) dimensions and function. These changes may be small, requiring a large study group. We measured LV parameters (LV volumes, LV ejection fraction (LV-EF), and left ventricular mass (LVM)) with two-dimensional echocardiography (2D-echo) and magnetic resonance imaging (MRI) in 50 patients. Based on the difference between the measurements, we determined the variance of the results and calculated the sample sizes needed to detect changes of baseline values. For the calculated and measured parameters we found significant differences between the two techniques: LV-EF and LVM were higher in 2D-echo, and LV dimensions were comparable. The sample size to detect relevant changes from baseline with MRI was significantly (P < 0.01) smaller than in 2D-echo. We conclude that MRI is superior in clinical studies on left ventricular dimensional and functional changes, since measurements are more reproducible and the required sample size is substantially smaller, thereby reducing costs.

Cardiac Volume↗
PubMed2001

Magnetic resonance planimetry of the vena contracta as a new approach to assessment of stenotic heart valves: an in vitro study.

Exact determination of the orifice area in stenotic valve disease is essential to guide therapy. With the standard imaging methods, the orifice area has to be calculated by empirically-derived formulas, which may be susceptible to changes in hemodynamic status, leading to wrong therapeutic decisions. We tested the ability of magnetic resonance imaging (MRI) to quantify the orifice area by planimetry of the proximal vena contracta (PVC) in an idealized, constant-flow model in a 1.0-T tomograph (Siemens Magnetom Expert). There was a close correlation of the PVC area in MRI and the true orifice area (r2 = 0.985), and agreement of the methods as measured by the Bland-Altman test was significant with a low systematic error of -0.02 cm2. We conclude that MRI planimetry of the PVC in stenotic valves in a constant-flow model may be used to reliably measure the orifice area.

Blood Flow Velocity↗
PubMed2001

Effect of NF-kappa B Inhibition on TNF-alpha-induced apoptosis and downstream pathways in cardiomyocytes.

Heart-specific inhibition of survival pathway gp130 was recently shown to sensitize transgenic mice towards stress stimuli, resulting in rapid onset of cardiac dilatation and heart failure. In order to identify further survival pathways we evaluated the role of transcription factor nuclear factor-kappa B (NF-kappa B) in tumour necrosis factor-alpha (TNF-alpha)-induced apoptosis of cardiomyocytes. TNF-alpha stimulation (10 ng/ml) of both H9c2 cells and primary cardiomyocytes isolated from neonatal Wistar rats resulted in rapid nuclear translocation of NF-kappa B complexes. The NF-kappa B complexes consisted of rel-proteins p50 and p65, as revealed by supershift analysis. Addition of proteasome inhibitor MG132 or adenoviral expression of a truncated I kappa B alpha (I kappa B Delta N) inhibited TNF-alpha-induced NF-kappa B nuclear translocation in a dose-dependent manner. Both neonatal cardiomyocytes and H9c2 cells were resistant to TNF-induced apoptosis. However, specific inhibition of NF-kappa B activation by Ad5-I kappa B alpha Delta N (MOI=50) or MG132 (5 microm) increased apoptosis as measured by subG1-assay (H9c2 cells) and annexin V binding/propidium iodide (neonatal cardiomyocytes, FACS-analysis: 7+/-2% to 26+/-5% annexin V positive/PI negative), respectively. TUNEL-assay double-stained with anti-alpha-sarcomeric actin confirmed apoptosis of neonatal cardiomyocytes. Furthermore, caspase-3 activation was increased by 52+/-7% in neonatal cardiomyocytes after TNF alpha+Ad5-I kappa B alpha Delta N compared to TNF alpha+Ad5-control treatment. Protein levels of hiAP1, hiAP2, x-iAP, bcl-2 and bcl-x(L) were neither downregulated by NF-kappa B inhibition nor upregulated by TNF-alpha stimulation. In summary, cardiomyocytes utilize transcription factor NF-kappa B to activate survival factors in the context of TNF-alpha stimulation. As locally increased levels of TNF-alpha have been detected in heart failure, NF-kappa B activity is essential for cellular homeostasis in the heart.

Animals↗