1,10-Phenanthroline-dithiine iridium and ruthenium complexes: synthesis, characterization and photocatalytic dihydrogen evolution.

We report the synthesis and the spectroscopic and electrochemical properties of six mononuclear iridium(iii) and ruthenium(ii) complexes bearing S,S'-extended phenanthroline ligands. Starting from 5,6-dibromide-1,10-phenanthroline, the dithiine derivatives N,N'-1,10-phenanthrolinedithiino[2,3-b]quinoxaline and N,N'-1,10-phenanthrolinedithiino[2,3-b]benzene were prepared by primary N,N'-complexation of the dibromo derivative and subsequent nucleophilic substitution at the complex. The photoluminescence of the phenanthroline-dithiine containing complexes shows distinctively increased lifetimes for all Ir(iii) and Ru(ii) complexes. The activity of the series of Ir(iii) and Ru(ii) complexes as photosensitizers in visible-light photocatalytic water reduction is demonstrated by dihydrogen evolution with a [Fe3(CO)12] catalyst and triethylamine as a sacrificial donor.

[Wine consumption and prevention of coronary artery disease]. / Weingenuss und Prävention der koronaren Herzkrankheit.

There is a J-shaped correlation between the amount of alcohol consumed per day and overall mortality risk and an inverse correlation between the amount of alcohol consumed per day and cardiovascular mortality. The evidence is stronger for men than for women. The correlations are independent of the type of alcoholic beverage predominantly consumed. Possible mechanisms explaining the cardioprotective, antiatherosclerotic effects of moderate alcohol consumption are inhibition of platelet aggregation, increase in serum high density lipoprotein (HDL) levels and prevention of diabetes mellitus. The two latter mechanisms can also explain a delayed progression of atherosclerosis due to alcohol consumption. The beneficial effects are counteracted by detrimental effects of alcohol on the incidence of cancer diseases, liver cirrhosis, violence and accidents; therefore, alcohol consumption in general cannot be recommended for prevention of cardiovascular diseases.

Ten-year observational follow-up of PROactive: a randomized cardiovascular outcomes trial evaluating pioglitazone in type 2 diabetes.

AIMS: To conduct a 10-year, observational follow-up of patients completing PROactive to investigate whether trends of cardiovascular benefit with pioglitazone and imbalances in specific malignancies persisted over time. METHODS: Macrovascular endpoints and malignancies were compared based on original randomization to pioglitazone or placebo and 'any' versus 'no' pioglitazone use for bladder and prostate cancer. RESULTS: Of 4873 patients completing the PROactive trial, 74% entered the follow-up. During follow-up (mean 7.8 years), there were no statistically significant differences in the primary [all-cause mortality, myocardial infarction (MI), cardiac intervention, stroke, major leg amputation, leg revascularization] or main secondary (death, MI, stroke) endpoints for subjects originally randomized to pioglitazone and placebo, except for leg amputations during follow-up [4.1% pioglitazone, 5.6% placebo; hazard ratio 0.74, 95% confidence interval (CI) 0.55-0.99; p = 0.046]. During follow-up, the incidence of total malignancies was similar between groups; bladder cancer was reported in 0.8% of patients (n = 14) in the pioglitazone versus 1.2% (n = 21) in the placebo group [relative risk (RR) 0.65, 95% CI 0.33-1.28], and prostate cancer was reported in 44 men (3.7%) in the pioglitazone versus 29 men (2.5%) in the placebo group (RR 1.47, 95% CI 0.93-2.34). CONCLUSIONS: The trends of macrovascular benefits of pioglitazone compared with placebo during PROactive did not persist in the absence of continued pioglitazone during this 10-year follow-up. Trends of decreased bladder cancer and increased prostate cancer were observed in the pioglitazone group during follow-up; however, these imbalances should be interpreted with caution because of the limitations of the observational study design.

Observational follow-up of the PROactive study: a 6-year update.

AIMS: The PROactive study investigated pioglitazone for secondary prevention of macrovascular events in type 2 diabetes mellitus. Pioglitazone showed a 10% (non-significant) relative risk (RR) reduction for the primary composite endpoint and a significant 16% reduction for the main secondary endpoint (death, myocardial infarction, stroke) after a mean 34.5 months. There was no difference in cumulative malignancy incidence, but an imbalance in bladder malignancies (pioglitazone 14, placebo 5). We present a pre-specified 6-year interim analysis of a 10-year observational follow-up. METHODS: Any patient completing PROactive was eligible. No study treatments were provided. A Cox proportional hazard model compared non-adjudicated macrovascular events (same endpoints as PROactive excluding acute coronary syndrome) based on original randomization. Malignancies were compared using conventional RR ratios. RESULTS: Of 5238 randomized patients, 3599 (74%) entered the follow-up. For the follow-up (mean 5.8 years) or combined double-blind and follow-up periods (≤9.5 years, mean 8.7), there were no statistically significant differences in primary or main secondary endpoints. For the combined period, a similar percentage of patients had any diagnosed malignancy (RR = 1.05, 95% CI [0.89, 1.24]) or bladder malignancy (RR = 1.06, 95% CI [0.59, 1.89]) in the pioglitazone and placebo groups. There were fewer cases of bladder malignancy with pioglitazone (15 [0.6%] vs. 19 [0.7%] for placebo) for the combined period when events diagnosed in the first 365 days were excluded, and fewer cases for the follow-up period alone (10 [0.5%] vs. 17 [1.0%] for placebo). Further analyses of pioglitazone use (including use during follow-up) found no significant difference in bladder malignancies between any and no pioglitazone use for the combined period. CONCLUSIONS: These data suggest that improved macrovascular outcomes seen with pioglitazone subside without continued pioglitazone treatment. The double-blind period bladder cancer imbalance did not persist in follow-up.

[Safety of ß-blockers. Prejudices and reality]. / Sicherheit von ß-Blockern. Vorurteile und Realität.

ß-blockers clearly prolong life in patients with heart failure and after myocardial infarction in all controlled prospective trials. Nevertheless, many colleagues and even more patients fear unwanted effects like low blood pressure, bradycardia, increased bronchial resistance, or erectile dysfunction. There are a limited number of serious side effects, which have to be recognized. In spite of these, we should encourage our patients, who profit from the beneficial actions of ß-blockers, to take them regularly. Some controversial aspects of ß-blocker therapy are discussed in the light of newer studies.

[70-year-old woman with cardiac hypertrophy and severe pulmonary hypertension: pre- or postcapillary?]. / 70-jährige Patientin mit Myokardhypertrophie und schwerer pulmonaler Hypertonie: Prä- oder postkapillär?

HISTORY AND ADMISSION FINDINGS: A 70-year-old female patient was admitted with progressive dyspnea and peripheral edema. The patient had a medical history of myocardial hypertrophy, diastolic dysfunction and concomitant pulmonary hypertension (PH). INVESTIGATIONS: The physical exam was suggestive of cardiac decompensation. Echocardiography showed myocardial hypertrophy, an enlarged left atrium as well as enlarged right-sided heart chambers. A prominent tricuspid regurgitation jet was present, and the estimated systolic right ventricular pressure was 65 mmHg. Invasive hemodynamic measurements showed a marked pressure elevation in the pulmonary circulation (mean PAP 51 mmHg), combined with an elevated left ventricular end-diastolic pressure (LVEDP) of 30 mmHg and a profound increase in the transpulmonary gradient (TPG, 21 mmHg). TREATMENT AND COURSE: The synopsis of these findings led to the diagnosis of postcapillary PH with a prominent precapillary involvement and cardiac decompensation. Due to signs of volume overload, an adequate diuretic therapy was initiated. The patient was recompensated and lost 7 kg of weight, which was associated with substantial clinical improvement. At invasive follow-up hemodynamic measurement, the patient's PAP was substantially decreased and almost reached normal values. The previously diagnosed precapillary involvement had disappeared. CONCLUSION: PH is a frequent phenomenon in patients with systolic and diastolic heart failure, and might initially appear as a combination of pre- and postcapillary involvement. The patients' volume status has a major influence on pulmonary hemodynamics. An adequate therapy of the underlying heart failure, especially an adequate diuresis, may have marked beneficial effects on pulmonary hemodynamics. Hemodynamic measurements should always be performed in compensated status.

[Validation of patients' knowledge after informed consent prior to coronary angiography]. / Überprüfung des Patientenwissens nach Aufklärung vor invasiver Koronarangiographie.

BACKGROUND AND OBJECTIVE: The informed consent of the patient is required before any medical intervention can be done. The impact of the provided information on the subsequent knowledge of the patient is regularly questioned. In the present investigation we aimed to determine the knowledge of the patients about invasive coronary angiography (CA) after they had been optimally vs. standard vs. not at all informed. PATIENTS AND METHODS: 300 consecutive patients who were admitted for planned CA were included. Of these, 150 in-patients were informed by especially trained physicians one day before CA and 50 out-patients were informed by their general practitioner or cardiologist several days before admission. 100 in-patients were included before they were informed. In a standardized interview the predefined knowledge of the patients was assessed by an independent physician before CA in previously informed patients and after hospital admission in non-informed patients. RESULTS: The differences in knowledge between informed in- and out-patients were low. Especially their knowledge about potential complications was not different. Generally, patients could remember less serious complications better than life-threatening ones. Two previously informed patients (1 %) affirmed that they were not informed. The knowledge of non-informed patients was much lower than the knowledge of patients who had been informed. CONCLUSION: The knowledge and remembrance of patients after having detailed information about medical interventions is limited. Optimization of the informative interview did not really improve this knowledge. In contrast to non-informed patients the provided information did, however, increase the knowledge.

[Phosphodiesterase-4 inhibitors: a new target in treatment of COPD]. / Phosphodiesterase-4-Hemmer - eine neue Therapieoption bei COPD.

Roflumilast is a new drug with innovative pharmacodynamic properties for use in patients with chronic obstructive pulmonary disease (COPD). By selective inhibition of phosphodiesterase-4 roflumilast targets inflammatory processes in COPD, with beneficial effects on smoking-induced bronchial inflammation, fibrotic remodeling, mucociliary malfunction and oxidative stress.

[Natriuretic peptides in the therapy of acute decompensated heart failure]. / Akut dekompensierte Herzinsuffizienz: klinischer Stellenwert einer Therapie mit natriuretischen Peptiden.

Heart failure is the most frequent cause of hospitalization in elderly population. Unlike the therapy of congestive heart failure, there was only a modest progress in the medical treatment for acutely decompensated heart failure over the past several decades. Moreover, current treatment is associated with many limitations in clinical practice. The family of natriuretic peptides consists of several structurally similar polypeptides (ANP, BNP, CNP, urodilatin, DNP). ANP and BNP are the most characterized substances and represent an important compensatory mechanisms in heart failure because of their vasodilatory, natriuretic and antiproliferative effects. Nesiritide is a recombinant human BNP which has been shown to be effective in treating heart failure in several clinical trials. However, a recent meta-analysis revealed a nesiritide-associated increased 30-day-mortality rate. The results of initial small-sized trials suggest beneficial hemodynamic effects of urodilatin in decompensated heart failure. Despite of being approved for the treatment of decompensated heart failure in some countries, the clinical relevance of nesiritide is currently unclear. Urodilatin might represent a potential alternative.