[Communication preferences of patients with prostate cancer : Preferences regarding the communication of bad news of patients with prostate cancer in Germany-results of an anonymous patient survey]. / Kommunikationspräferenzen von Patienten mit Prostatakrebs : Ergebnisse einer anonymen Patientenbefragung unter Patienten mit Prostatakrebs zu ihren Kommunikationspräferenzen.

BACKGROUND: The communication of bad medical news represents a burdening situation for both patients and physicians which may lead to hurdles in their communication. The questionnaire Measure of Patients' Preferences (MPP-D, validated German translation) was developed to investigate patients' preferences regarding the communication of bad news. OBJECTIVES: The preferences regarding the communication of bad news among patients with prostate cancer was assessed. MATERIALS AND METHODS: Anonymous survey, where approximately 70 office-based urologists were asked to distribute the MPP-D questionnaire to about 20 of their patients with prostate cancer. In addition, information on social demographics was retrieved in order to investigate the influence on communication preferences. RESULTS: In total, 709 questionnaires were evaluated (>50 % return). The majority of patients had clear preferences concerning privacy of the setting, completeness, and unambiguity of information provided and assessment of their subjective information needs. Larger individual differences were observed regarding preferences for emotional support offered by the physician and involvement of family which was also influenced by age and education of the patients. CONCLUSION: This is the first large, multicenter survey of prostate cancer patients in Germany regarding their preferences for communication of bad news. The results confirm previous reports on the importance of cultural affiliation, age, and education as influencing factors.

[Quality of life of patients with prostate cancer under androgen deprivation with GnRH analogues: Results of the noninterventional study TRIPTOSIX]. / Lebensqualität von Patienten mit Prostatakarzinom unter Androgendeprivation mit GnRH-Analoga : Ergebnisse der nicht-interventionellen Studie TRIPTOSIX.

BACKGROUND: In Germany, data on the quality of life (QoL) of patients with advanced prostate cancer (PCa) under therapy with gonadotropin-releasing hormone (GnRH) analogues are limited. OBJECTIVES: Androgen deprivation (ADT) is a palliative therapy for patients with advanced PCa, which is given over long periods and usually continued in combination with other therapies even after progression of the disease. The present study aimed to assess prospectively (over 1 year) different aspects of patients' QoL therapy with triptorelin in daily practice. PATIENTS AND METHODS: This prospective, noninterventional study at 129 centers in Germany included 608 patients with advanced PCa treated with triptorelin. Quality of life was assessed at baseline and after 6 and 12 months, using validated EORTC QLQ-C30 and QLQ-PR25 questionnaires. Predefined subgroup analyses were performed to assess the impact of demographics, anamnestic and clinical parameters on QoL. RESULTS AND DISCUSSION: The majority of patients with PCa under therapy with triptorelin showed generally stable global QoL over 1 year; approximately one-quarters of the patients had a clinically relevant improvement of their global QoL. In patients without previous PCa therapy and GnRH analogue treatment, significant improvements in global QoL were seen. At the same time, these patients also reported increased treatment-related symptoms. These data indicate that the perception of global QoL is not only influenced by subjective impairment through ADT-related side effects.

[Cross-sectional analysis of routine treatment for prostate cancer patients: CAPRIS - a healthcare research project of the IQUO]. / Querschnittsanalyse zur Routinebehandlung von Prostatakrebspatienten : CAPRIS - ein Versorgungsforschungsprojekt des IQUO.

BACKGROUND: Different practices for the treatment of prostate cancer patients exist in Germany. OBJECTIVES: The aim of this analysis was to investigate current practice for the treatment of patients with prostate cancer in urological IQUO partner practices (Interest Group for Quality Assurance in the Work of Office-based Uro-oncologists in Germany) dependent on tumor stage and risk factors. The analysis focused on T1/T2 and T3/T4 patients. In addition, applied therapies were analyzed based on risk group classification (CAPRIS, cancer of the prostate identification screening). MATERIALS AND METHODS: This retrospective cross-sectional analysis includes 1000 patients with prostate cancer with at least 12 months of documentation from the OnkoDataMed (ODM) database between February 2008 and May 2012. The 122 IQUO medical practices included were randomly selected; maximally 50 patients per practice were included in the analysis. The database was analyzed in terms of localized T1/T2 tumors and advanced T3/T4 tumors. Risk groups were formed according to parameters of the initial diagnosis including PSA value, tumor stage, and Gleason score. Descriptive statistics were performed to analyze all parameters. RESULTS AND CONCLUSIONS: As expected, PSA is the critical parameter for follow-up and therapy monitoring. Newer therapeutic options have only been initiated to a limited extent. Differentiated risk assessment has not been sufficiently used; however, it does provide a good opportunity for more individualized therapy in the future.

A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group.

BACKGROUND AND METHODS: Although generalized convulsive status epilepticus is a life-threatening emergency, the best initial drug treatment is uncertain. We conducted a five-year randomized, double-blind, multicenter trial of four intravenous regimens: diazepam (0.15 mg per kilogram of body weight) followed by phenytoin (18 mg per kilogram), lorazepam (0.1 mg per kilogram), phenobarbital (15 mg per kilogram), and phenytoin (18 mg per kilogram). Patients were classified as having either overt generalized status epilepticus (defined as easily visible generalized convulsions) or subtle status epilepticus (indicated by coma and ictal discharges on the electroencephalogram, with or without subtle convulsive movements such as rhythmic muscle twitches or tonic eye deviation). Treatment was considered successful when all motor and electroencephalographic seizure activity ceased within 20 minutes after the beginning of the drug infusion and there was no return of seizure activity during the next 40 minutes. Analyses were performed with data on only the 518 patients with verified generalized convulsive status epilepticus as well as with data on all 570 patients who were enrolled. RESULTS: Three hundred eighty-four patients had a verified diagnosis of overt generalized convulsive status epilepticus. In this group, lorazepam was successful in 64.9 percent of those assigned to receive it, phenobarbital in 58.2 percent, diazepam plus phenytoin in 55.8 percent, and phenytoin in 43.6 percent (P=0.02 for the overall comparison among the four groups). Lorazepam was significantly superior to phenytoin in a pairwise comparison (P=0.002). Among the 134 patients with a verified diagnosis of subtle generalized convulsive status epilepticus, no significant differences among the treatments were detected (range of success rates, 7.7 to 24.2 percent). In an intention-to-treat analysis, the differences among treatment groups were not significant, either among the patients with overt status epilepticus (P=0.12) or among those with subtle status epilepticus (P=0.91). There were no differences among the treatments with respect to recurrence during the 12-hour study period, the incidence of adverse reactions, or the outcome at 30 days. CONCLUSIONS: As initial intravenous treatment for overt generalized convulsive status epilepticus, lorazepam is more effective than phenytoin. Although lorazepam is no more efficacious than phenobarbital or diazepam plus phenytoin, it is easier to use.

Combination Hemotherapy and Mortality Prevention (CHAMP) Study Rationale and Design.

It is now agreed that the majority of acute myocardial infarctions result from intracoronary thrombosis at sites of atherosclerotic plaque that have been disrupted. In 1947 Nicol and Fassett published the first clinical paper suggesting that agents interfering with blood coagulation could prevent myocardial infarction in patients at risk. Scores of subsequent clinical trials were performed to assess the efficacy of anticoagulants and antiplatelet agents in preventing death and reinfarction in survivors of acute myocardial infarction. Despite these efforts no agreement exists on whether these strategies are beneficial and, if so, which is superior. The primary obstacle to progress in this field has been the failure of nearly all trials to enroll the large numbers of subjects required to demonstrate a survival benefit. The large sample size requirement derives from two inescapable facts: mortality rates following acute infarction, though variable, are generally low and the potential benefit of these agents in preventing mortality is small. Combining oral anticoagulants with antiplatelet agents (combination hemotherapy) may significantly enhance their antithrombotic effect. Clinical trials of combination hemotherapy have demonstrated superiority over anticoagulant monotherapy in the setting of stroke prevention in patients with prosthetic heart valves. Similar benefit was not observed in trials studying stroke prevention in nonvalvular atrial fibrillation and vascular morbidity in patients surviving an acute myocardial infarction. The failure of these latter studies may relate to the particularly low intensity of warfarin administered in combination with aspirin. This trial proposes to demonstrate that the combination of oral anticoagulation, administered in a moderate dose intensity, and antiplatelet therapy is superior to aspirin monotherapy in reducing overall mortality following acute myocardial infarction.

Elicitor-stimulated ion fluxes and O2- from the oxidative burst are essential components in triggering defense gene activation and phytoalexin synthesis in parsley.

Fungal elicitor stimulates a multicomponent defense response in cultured parsley cells (Petroselinum crispum). Early elements of this receptor-mediated response are ion fluxes across the plasma membrane and the production of reactive oxygen species (ROS), sequentially followed by defense gene activation and phytoalexin accumulation. Omission of Ca2+ from the culture medium or inhibition of elicitor-stimulated ion fluxes by ion channel blockers prevented the latter three reactions, all of which were triggered in the absence of elicitor by amphotericin B-induced ion fluxes. Inhibition of elicitor-stimulated ROS production using diphenylene iodonium blocked defense gene activation and phytoalexin accumulation. O2- but not H2O2 stimulated phytoalexin accumulation, without inducing proton fluxes. These results demonstrate a causal relationship between early and late reactions of parsley cells to the elicitor and indicate a sequence of signaling events from receptor-mediated activation of ion channels via ROS production and defense gene activation to phytoalexin synthesis. Within this sequence, O2- rather than H2O2 appears to trigger the subsequent reactions.

Cardiovascular diseases in women: an equal opportunity killer.

Despite the public perception that heart disease primarily affects men, as women age, their risk equals and eventually outpaces that of men. Gender-specific differences in cardiovascular diseases have been reported related to onset, diagnosis, therapy, pharmacokinetics, adverse drug reactions, and mortality rates, but most of these differences are unexplained. Research in coronary heart disease has been performed almost exclusively in men, but the findings have been used to set standards for both sexes. Studies suggest a 50% reduction in heart disease risk among women receiving postmenopausal hormone replacement therapy.

Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure.

BACKGROUND: Asymptomatic ventricular arrhythmias in patients with congestive heart failure are associated with increased rates of overall mortality and sudden death. Amiodarone is now used widely to prevent ventricular tachycardia and fibrillation. We conducted a trial to determine whether amiodarone can reduce overall mortality in patients with congestive heart failure and asymptomatic ventricular arrhythmias. METHODS: We used a double-blind, placebo-controlled protocol in which 674 patients with symptoms of congestive heart failure, cardiac enlargement, 10 or more premature ventricular contractions per hour, and a left ventricular ejection fraction of 40 percent or less were randomly assigned to receive amiodarone (336 patients) or placebo (338 patients). The primary end point was overall mortality, and the median follow-up was 45 months (range, 0 to 54). RESULTS: There was no significant difference in overall mortality between the two treatment groups (P = 0.6). The two-year actuarial survival rate was 69.4 percent (95 percent confidence interval, 64.2 to 74.6) for the patients in the amiodarone group and 70.8 percent (95 percent confidence interval, 65.7 to 75.9) for those in the placebo group. At two years, the rate of sudden death was 15 percent in the amiodarone group and 19 percent in the placebo group (P = 0.43). There was a trend toward a reduction in overall mortality among the patients with nonischemic cardiomyopathy who received amiodarone (P = 0.07). Amiodarone was significantly more effective in suppressing ventricular arrhythmias and increased the left ventricular ejection fraction by 42 percent at two years. CONCLUSIONS: Although amiodarone was effective in suppressing ventricular arrhythmias and improving ventricular function, it did not reduce the incidence of sudden death or prolong survival among patients with heart failure, except for a trend toward reduced mortality among those with nonischemic cardiomyopathy.

Perception and transduction of an elicitor signal in cultured parsley cells.

Treatment of cultured parsley cells or protoplasts with a purified extracellular glycoprotein from Phytophthora megasperma f.sp. glycinea induces the transcription of the same set of defence-related genes as is activated in parsley leaves upon infection. Elicitor activity was shown to reside in a specific portion of the protein moiety which was isolated, sequenced and synthesized. Partial cDNAs encoding the entire mature protein as well as other related proteins have been isolated, indicating the presence of a small gene family. The elicitor-active oligopeptide is located in the C-terminal portion of the deduced amino acid sequence. Binding of the elicitor to target sites on the parsley plasma membrane appears to be the initial event in defence gene activation. The subsequent intracellular transduction of the elicitor signal was shown to involve rapid and transient influxes of Ca2+ and H+, as well as effluxes of K+ and Cl-. Inhibition of elicitor-induced ion fluxes by channel blockers also inhibited phytoalexin synthesis, while stimulation of similar ion fluxes by treatment of cells or protoplasts with the polyene antibiotic, amphotericin B, induced the production of phytoalexins and activated the complete set of defence-related genes in the absence of elicitor.

Veterans Affairs congestive heart failure antiarrhythmic trial. CHF STAT Investigators.

This is a prospective, double-blind, placebo-controlled trial to determine the effect of antiarrhythmic drug therapy on mortality in patients with congestive heart failure and ventricular arrhythmia. Patients will be assigned to receive either amiodarone or placebo. Eligible patients include those with ischemic and nonischemic congestive heart failure and with > or = 10 ventricular premature beats per hour. All patients must have shortness of breath with minimal exertion or paroxysmal nocturnal dyspnea, a left ventricular internal dimension (LVIDd) by echocardiogram of > or = 55 mm or a cardiothoracic ratio of > 0.5 and an ejection fraction of < or = 40%. All patients will receive vasodilator therapy, unless they find it intolerable. Patients will be entered into the study for 2.5 years and followed for an additional 2 years. Drug therapy will be continued for all patients throughout the entire study unless adverse reactions occur that necessitate individualized treatment. The expectation is that 674 patients will be entered into the study from 25 participating centers. This sample size will allow for the detection of a 33% decrease in 2-year mortality (20% vs 30%) in the treated patients compared with those in the placebo group, with a power of 0.90 and a 2-sided alpha level of 0.05. Intermittent Holter monitoring, radionuclide ventriculograms, pulmonary function tests, echocardiograms, and blood tests, including arterial blood gases, will be required for each patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators.

BACKGROUND: Nonrheumatic atrial fibrillation is common among the elderly and is associated with an increased risk of stroke. We investigated whether anticoagulation with warfarin would reduce this risk. METHODS: We conducted a randomized, double-blind, placebo-controlled study to evaluate low-intensity anticoagulation with warfarin (prothrombin-time ratio, 1.2 to 1.5) in 571 men with chronic nonrheumatic atrial fibrillation; 525 patients had not previously had a cerebral infarction, whereas 46 patients had previously had such an event. The primary end point was cerebral infarction; secondary end points were cerebral hemorrhage and death. RESULTS: Among the patients with no history of stroke, cerebral infarction occurred in 19 of the 265 patients in the placebo group during an average follow-up of 1.7 years (4.3 percent per year) and in 4 of the 260 patients in the warfarin group during an average follow-up of 1.8 years (0.9 percent per year). The reduction in risk with warfarin therapy was 0.79 (95 percent confidence interval, 0.52 to 0.90; P = 0.001). The annual event rate among the 228 patients over 70 years of age was 4.8 percent in the placebo group and 0.9 percent in the warfarin group (risk reduction, 0.79; P = 0.02). The only cerebral hemorrhage occurred in a 73-year-old patient in the warfarin group. Other major hemorrhages, all gastrointestinal, occurred in 10 patients: 4 in the placebo group, for a rate of 0.9 percent per year, and 6 in the warfarin group, for a rate of 1.3 percent per year. There were 37 deaths that were not preceded by a cerebral end point--22 in the placebo group and 15 in the warfarin group (risk reduction, 0.31; P = 0.19). Cerebral infarction was more common among patients with a history of cerebral infarction (9.3 percent per year in the placebo group and 6.1 percent per year in the warfarin group) than among those without such a history. CONCLUSIONS: Low-intensity anticoagulation with warfarin prevented cerebral infarction in patients with nonrheumatic atrial fibrillation without producing an excess risk of major hemorrhage. This benefit extended to patients over 70 years of age.

Congestive heart failure: survival trial of antiarrhythmic therapy (CHF STAT). The CHF STAT Investigators.

This study is a prospective, double-masked, randomized, clinical trial to determine the effect of anti-arrhythmic drug therapy on mortality in patients with congestive heart failure and ventricular arrhythmia. Patients will be assigned to receive either amiodarone or placebo. Eligible patients include those with ischemic and nonischemic congestive heart failure (New York Heart Association class III or VI) and with 10 or more ventricular premature beats per hour. All patients must have shortness of breath with minimal exertion or paroxysmal nocturnal dyspnea, a left ventricular internal dimension (LVIDd) by echocardiogram of 55 mm or greater (> or = 55 mm) or a CT ratio of greater than 0.5, and an ejection fraction of 40% of less. Patients will be entered into the study for 2.5 years and followed for an additional 2 years. Drug therapy will be continued for all patients throughout the entire study unless adverse reactions occur that necessitate individualized treatment. The expectation is that 674 patients are to be entered into the study from 25 participating centers. This sample size will allow for the detection of a 33% decrease in 2-year mortality (20% vs. 30%) in the treated patients as compared to those in the placebo group with a power of 0.90 and a two-sided alpha level of 0.05. Intermittent Holter monitoring, radionuclide ventriculograms, pulmonary function tests, echocardiograms, and blood tests, including arterial blood gases, will be required for each patient. The study analysis will address differences in total mortality, cardiac mortality, and sudden cardiac death between patients receiving anti-arrhythmic drug therapy and those receiving placebo. Other factors to be examined include the effects of antiarrhythmic therapy on suppression of arrhythmias, on ejection fraction, and relation of ischemic events to mortality.

Mapping of the epitope/paratope interactions of a monoclonal antibody directed against adenosine 3',5'-monophosphate.

A series of systematically modified cyclic AMP (cAMP) analogues, including newly synthesized benzimidazole ribofuranosyl 3',5'-monophosphates was used to map the essential molecular interactions between cAMP and the monoclonal antibody 4/2C2 (mab 4/2C2) directed against 2'-O-succinoyl cAMP [Colling, Gilles, Nass, Moka & Jaenicke (1988) Second Messengers Phosphoproteins 12, 123-133]. Its paratope binds the purine base in syn conformation by dipole-dipole interactions and hydrophobic forces and/or stacking interactions. The ribose phosphate moiety is recognized by a combination of charge interactions and H-bonds to the exocyclic and the 5'-oxygen atoms and a hydrophobic interaction at the 2'-position. There is no regioselectivity for the exocyclic oxygen atoms. Compared with the known types of binding, mab 4/2C2 thus shows a new combination of molecular interactions which may be the basis of its strikingly specific recognition and binding of the cyclic adenylates. On this account mab 4/2C2 may become an important tool in studies on cAMP metabolism.

Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis. Veterans Affairs Cooperative Studies Program 309 Trialist Group.

OBJECTIVE: To determine whether carotid endarterectomy provides protection against subsequent cerebral ischemia in men with ischemic symptoms in the distribution of significant (greater than 50%) ipsilateral internal carotid artery stenosis. DESIGN: Prospective, randomized, multicenter trial. SETTING: Sixteen university-affiliated Veterans Affairs medical centers. PATIENTS: Men who presented within 120 days of onset of symptoms that were consistent with transient ischemic attacks, transient monocular blindness, or recent small completed strokes between July 1988 and February 1991. Among 5000 patients screened, 189 individuals were randomized with angiographic internal carotid artery stenosis greater than 50% ipsilateral to the presenting symptoms. Forty-eight eligible patients who refused entry were followed up outside of the trial. OUTCOME MEASURES: Cerebral infarction or crescendo transient ischemic attacks in the vascular distribution of the original symptoms or death within 30 days of randomization. INTERVENTION: Carotid endarterectomy plus the best medical care (n = 91) vs the best medical care alone (n = 98). RESULTS: At a mean follow-up of 11.9 months, there was a significant reduction in stroke or crescendo transient ischemic attacks in patients who received carotid endarterectomy (7.7%) compared with nonsurgical patients (19.4%), or an absolute risk reduction of 11.7% (P = .011). The benefit of surgery was more profound in patients with internal carotid artery stenosis greater than 70% (absolute risk reduction, 17.7%; P = .004). The benefit of surgery was apparent within 2 months after randomization, and only one stroke was noted in the surgical group beyond the 30-day perioperative period. CONCLUSIONS: For a selected cohort of men with symptoms of cerebral or retinal ischemia in the distribution of a high-grade internal carotid artery stenosis, carotid endarterectomy can effectively reduce the risk of subsequent ipsilateral cerebral ischemia. The risk of cerebral ischemia in this subgroup of patients is considerably higher than previously estimated.

Measurement of 3':5'cyclic AMP in biological samples using a specific monoclonal antibody.

A fast and sensitive radioimmunoassay for 3':5'cyclic AMP based on a monoclonal antibody has been worked out. Mice were immunized with protein-conjugated 2'-O-succinyl-3':5'-cyclic AMP. The monoclonal antibody detects 0.1 and 1 pmole cAMP with succinyl cAMP (125I)iodotyrosine methyl ester and (3H) cAMP, respectively, as tracers. It shows no cross-reactivity to other adenosine nucleotides up to the millimolar range; cGMP interferes only if present at a 500 fold excess. Plant and animal tissue samples as well as adenylate cyclase activity were analysed directly or after appropriate purification in case of interfering substances. Cyclic AMP levels measured in various tissues by the antibody binding assay correspond to those obtained by HPLC determination using fluorescent etheno-cAMP.