[Assessment of coronary calcification is important--contra].
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Biomedical subjects
Publications and source records attributed to E Erdmann.
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Activation of presynaptic metabotropic glutamate receptors (mGluRs) leads to a powerful inhibition of glutamate release from many synaptic terminals throughout the CNS. mGluRs as autoreceptors are believed to provide a negative feedback system that prevents potentially toxic accumulation of glutamate in the extracellular space during synchronous synaptic activity such as epileptic seizures. In this study we analyzed the function of presynaptic mGluR8 on terminals of the lateral perforant pathway in the pilocarpine model of limbic epilepsy. Field excitatory postsynaptic potentials (fEPSPs) recorded in hippocampal slices of rats that developed spontaneous recurrent seizures after pilocarpine-induced status epilepticus (SRS group) showed a significantly reduced sensitivity to Group III mGluR agonists and severe mossy fiber sprouting. The Group III mGluR agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4, 10 microM) depressed fEPSPs in the SRS group only by 26 +/- 21% compared to 50 +/- 18% in untreated rats. Similarly, the mGluR8 preferring agonist (R,S)-4-phosphonophenylglycine (PPG, 5 microM) was significantly less effective in slices from SRS rats (43 +/- 4% vs. 83 +/- 5%). Concentration-response curves for L-AP4 revealed that the EC(50) values were not different between the control and SRS group (13 +/- 7 microM vs. 9 +/- 9 microM), while the maximal depressing effect was significantly reduced. The remaining depressing effect of L-AP4 in the SRS group could be blocked by the Group III specific antagonists (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) and alpha-methyl-L-AP4 (MAP4). Rats that did not develop SRS following pilocarpine-induced status epilepticus were indistinguishable from control rats: fEPSPs were highly sensitive to L-AP4 and there was no mossy fiber sprouting. The results show that pilocarpine-induced status epilepticus can lead to a downregulation of mGluR8 and suggest that the condition of SRS is associated with a deteriorated autoregulation of glutamate release.
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A 41-year-old male patient presented with fever of unknown origin which had been present for 5 months. The primary diagnostic procedures did not identify an infectious focus. After a lag phase of 13 days, blood cultures became positive for Actinobacillus actinomycetemcomitans, which belongs to the HACEK group of microorganisms. According to the DUKE criteria, infective endocarditis was diagnosed despite negative transesophageal echocardiography (TEE). The sensitivity of TEE is estimated between 86 and 94%. An infected tooth was extracted as a possible focus, and the patient was treated with i.v. antibiotics for 5 weeks according to the guidelines of the AHA and ACC. The fever was permanently terminated, and the further course of the patient was uneventful. Despite negative TEE, the diagnosis "infective endocarditis" should not be rejected, and blood cultures should be grown for up to 30 days.
Recent studies provide evidence that infectious agents play a causal role in the pathogenesis of atherosclerosis. In this respect, a chronic persistent Chlamydia pneumoniae infection, indicated by the presence of chlamydial heat shock protein 60 (cHSP 60), is of central interest. Both cHSP60 and endogenous human (h) HSP60 are upregulated under stress conditions in intimal cells and serve as a target for cross-reactive cytotoxic HSP-serum-antibodies. Therefore, the present study evaluates the expressions of both HSP60 homologues in advanced human coronary lesions and a correlation between intimal tissuebound protein and serum antibodies (Ab) to HSP65. Coronary atherectomy specimens retrieved from 114 primary target lesions of patients with acute coronary syndrome (ACS; n=46) or stable angina (SA; n=68) were assessed immunohistochemically for the presence of cHSP60 and hHSP60. Chronic persistency of Chlamydia pneumoniae was additionally examined by transmission electron microscopy. Blood samples from30 patients were tested for anti-Chlamydia pneumoniae-IgG/IgA- and anti-HSP65-Ab titers and for serum CRP levels. Coronary plaques revealed immunoreactive cHSP60 in 47% and hHSP60 in 57% of the lesions colocalized within macrophages/foam cells. Chlamydia in foam cells most often presented ultrastructural patterns that pointed to the persistency of the pathogen. Intact, non-atherosclerotic vessels showed no signals. Mean expressions were 3.1% for cHSP60 and 3.3% for hHSP60. As a central finding, the expression of both HSP homologues was significantly (each p<0.001) higher in ACS lesions compared to SA lesions (cHSP60: 6.2 vs 1.0%, and hHSP60: 7.2 vs 0.7%). Moreover, we found positive correlations between both determinants in ACS and SA lesions (r=0.41, r=0.37; p<0.01). Most interestingly, cHSP60 revealed no relationship with anti-Chlamydia pneumoniae-IgG/IgA titers, whereas expression of cHSP60 as well as that of hHSP60 correlated with anti-HSP65-Ab titers (r=0.50, p<0.01, and r=0.42, p<0.05, respectively).cHSP60 and hHSP60 colocalize within coronary primary atheroma, most prevalent in lesions associated with ACS. For the first time, our data demonstrate a significant correlation between the intimal expression of these HSP60 homologues and serum HSP65 antibodies, thereby suggesting that humoral immune reactions to bacterial and human HSPs may play an important role in coronary atherosclerosis and plaque instability.
In patients with coronary artery disease undergoing noncardiac surgery, beta-blockers decrease perioperative mortality and nonfatal myocardial infarction. It is presently unknown whether beta-blockers reduce perioperative risk in patients with chronic heart failure. Thus, data of the CIBIS II study were analyzed regarding the effect of bisoprolol on perioperative outcome in patients with moderate to severe heart failure. A total of 2647 patients with heart failure in New York Heart Association (NYHA) class III-IV and left ventricular ejection fraction < or =35% were randomized to bisoprolol or placebo in a double-blind randomized study. Of these patients, 165 underwent surgery (bisoprolol, n = 87; placebo, n = 78). In patients undergoing surgery, mortality was not different between the placebo- and bisoprolol-treated group (7.7% vs 5.8%, p = 0.76). Neither postoperative hospital admission (placebo, 24.4%; bisoprolol, 34.5%, p = 0.17) nor time to postoperative hospital admission (placebo, < or =30 days, n = 2; 31-180 days, n=11; >180 days, n = 6; bisoprolol, n = 9/ 10/11; p = 0.14) were reduced by bisoprolol. Compared to coronary artery disease, perioperative beta-blockade has little effect in patients with chronic heart failure. Therefore, a controlled randomized trial with perioperative beta-blocker treatment in heart failure patients is warranted to further test this hypothesis.
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BACKGROUND AND OBJECTIVE: An early detection of patients with left-ventricular (LV) dysfunction is essential for effective treatment of congestive heart failure. The B-type natriuretic peptide (BNP) was described as a strong diagnostic parameter of LV-dysfunction. Aim of this study was to compare the diagnostic value of BNP and the aminoterminal part of pro-BNP (NT-pro-BNP) within an heterogenous patient population. SUBJECTS AND METHODS: NT-pro-BNP and BNP were measured in 150 hospitalized cardiologic patients (age-median 64 years, 109 male versus 41 female). The values were correlated with clinical and haemodynamic parameters of the invasively determined LV-function. RESULTS: Patients with pathologic haemodynamic values of the LV-function had significantly higher NT-pro-BNP and BNP levels than patients with normal haemodynamic parameters. In our study population a severe systolic LV-dysfunction (ejectionfraction EF<40 %) could be detected with a sensitivity and specifity of 100 % and 64 % by NT-pro-BNP and 100 % and 45 % by BNP. Sensitivity and specifity for the detection of any systolic dysfunction (EF<60 %) and of a systolic or diastolic dysfunction, respectively, were 94 %, 37 % and 88 %, 41 % for NT-pro-BNP (94 %, 40 % and 84 %, 44 % for BNP). The corresponding negative predictive values were 100 %, 96 % and 71 % for NT-pro-BNP and 100 %, 96 % and 68 % for BNP. CONCLUSION: NT-pro-BNP and BNP were highly sensitive diagnostic parameters with a very good negative predictive value for LV-dysfunction. Because of the uncomplicated measurement, they could be used effectively to rule out LV-dysfunction in cardiovascular high risk patients by general practitioners.
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Hypertension is an important risk factor for erectile dysfunction (ED). Consequently, there is a high coincidence between hypertension and ED. Oral sildenafil (Viagra) is an effective treatment for ED in patients with treated or untreated hypertension. The most common adverse events of sildenafil (headache, flushing, hypotension) result from its moderate vasodilating properties. The concomitant use of sildenafil and organic nitrates is contraindicated because it may lead to a potentiation of the decreases in blood pressure and thus cause life-threatening hypotension. In contrast, the concomitant use of sildenafil and different classes of antihypertensive agents (beta-blockers, alpha-blockers, diuretics, ACE inhibitors, calcium antagonists) may lead to additive but not to potentiating blood pressure decreases. Thus, this combination is unlikely to cause clinically significant hypotension or an increased incidence of adverse events. Sildenafil is an effective and well-tolerated treatment for ED in patients taking concomitant antihypertensive medication, including those on multidrug regimens.
The selective beta blockers metoprolol, bisoprolol and atenolol, but also the non-selective beta blocker carvedilol, are drugs with individually specific properties that are widely prescribed for a wide range of indications. Modern beta blockers are safe drugs with a low profile of side effects, which, applied with proper consideration being given to contraindications, rarely produce serious side effects such as bradyarrhythmia, bronchial obstruction, or aggravation of heart failure. Their prognostic benefit, for example, in the treatment of post-myocardial infarction patients, or in cardiac insufficiency, has been demonstrated in large randomized clinical trials.
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