[Interprofessional symptom management at the end of life]. / Interprofessionelle Symptomkontrolle am Lebensende.

At the end of life patients often show distressful symptoms which significantly reduce their quality of life. The goal of all healthcare professionals should be to recognize the beginning of this end of life period in order to provide good symptom management. For this purpose, existing symptoms have to be recorded, suitable therapeutic goals have to be defined for the current situation and potential therapeutic strategies have to be individually formulated. Besides the identification of underlying causes with the possibility of causal treatment, a symptom-based therapy is often necessary. Therapeutic approaches of different professions should be equally considered and should additionally be used for the benefit of the patient.

[Potential of specialized outpatient palliative care]. / Möglichkeiten der spezialisierten ambulanten Palliativversorgung.

Palliative care patients with incurable advanced disease suffering from complex symptoms can receive specialized outpatient palliative care in addition to the existing ambulatory care system. Qualified physicians and nurses care for patients and their dependents in cooperation with other professionals. In addition to a 24/7 on-call service for emergencies or acute crises, patients and their dependents are offered regular visits.

[Interprofessional symptom management at the end of life]. / Interprofessionelle Symptomkontrolle am Lebensende.

At the end of life patients often show distressful symptoms which significantly reduce their quality of life. The goal of all healthcare professionals should be to recognize the beginning of this end of life period in order to provide good symptom management. For this purpose, existing symptoms have to be recorded, suitable therapeutic goals have to be defined for the current situation and potential therapeutic strategies have to be individually formulated. Besides the identification of underlying causes with the possibility of causal treatment, a symptom-based therapy is often necessary. Therapeutic approaches of different professions should be equally considered and should additionally be used for the benefit of the patient.

Posaconazole prophylaxis in patients with acute myelogenous leukaemia--results from an observational study.

Patients with acute myelogenous leukaemia (AML) and neutropenia after chemotherapy are at high risk for life-threatening invasive fungal disease (IFD), in particular, invasive aspergillosis (IA). The aim of the study was to evaluate data on characteristics, risk factors, complications and additional antifungal treatment of patients with AML receiving posaconazole prophylaxis (PP) after chemotherapy in an actual clinical setting. A retrospective single-centre observational study on 40 patients with AML, median age 66 years, was conducted. PP 200 mg three times daily was given routinely. After 76 cycles of remission induction chemotherapy followed by PP, median duration of 31 days (range 6-61 days), no fatal case occurred. The majority of patients had at least one additional risk factor for IFD and during 32 cycles (42.1%), three risk factors were present. During 40 therapy cycles (52.6%), fever of unknown origin occurred. Pneumonia was diagnosed after 23 cycles (30.3%), thereof one case of proven IA (1.3%). PP was interrupted in 25 cycles (32.9%) and was followed by systemic antifungal therapy with different agents, with a median duration 15 days (range: 6-32 days). PP appears to be an effective and well-tolerated protection against IFD for AML patients under natural clinical conditions.

Adenovirus-mediated gene transfer of pathogen-associated molecular patterns for cancer immunotherapy.

The delivery of stimulatory signals to dendritic cells (DCs) in the tumor microenvironment could be an effective means to break tumor-induced tolerance. The work presented here evaluates the immunostimulatory properties of pathogen-associated molecular patterns (PAMPs), microbial molecules which bind Toll-like receptors and deliver activating signals to immune cells, when expressed in tumor cells using adenoviral (Ad) vectors. In vitro, transduction of A549 tumor cells with Ad vectors expressing either flagellin from Listeria monocytogenes or P40 protein from Klebsiella pneumoniae induced the maturation of human monocyte-derived DCs in co-cultures. In mixed lymphocyte reactions (MLRs), Ad-flagellin and Ad-P40 transduction of tumor cells stimulated lymphocyte proliferation and the secretion of IFN-gamma. In vivo, these vectors were used either as stand-alone immunoadjuvants injected intratumorally or as vaccine adjuvants combined with a tumor antigen-expressing vector. When Ad-PAMPs were administered intratumorally to mice bearing subcutaneous syngeneic B16F0-CAR (cocksackie-adenovirus receptor) melanomas, tumor progression was transiently inhibited by Ad-P40. In a therapeutic vaccine setting, the combination of Ad-MUC1 and Ad-PAMP vectors injected subcutaneously delayed the growth of implanted RenCa-MUC1 tumors and improved tumor rejection when compared with vaccination with Ad-MUC1 alone. These results suggest that Ad-PAMPs could be effective immunoadjuvants for cancer immunotherapy.

Modified vaccinia virus Ankara as a vector for suicide gene therapy.

Modified vaccinia virus Ankara (MVA) has been used successfully to express various antigens for the development of vaccines. Here we show that MVA can also be used as an efficient vector for the transfer of suicide genes to cancer cells. We have generated a new and highly potent suicide gene, FCU1, which encodes a fusion protein derived from the yeast cytosine deaminase and uracil phosphoribosyltransferase genes. We now describe the therapeutic benefit of using MVA to deliver and express the FCU1 gene in cancer cells. MVA-mediated transfer of the FCU1 gene to various human tumor cells results in the production of a bifunctional intracellular enzyme, such that exposure to the prodrug 5-FC suppresses the growth of the tumor cells both in vitro and in vivo. Moreover, we report a more potent tumor growth delay at lower doses of 5-FC using MVA-FCU1 in comparison to adenovirus encoding FCU1. Prolonged therapeutic levels of cytotoxic 5-FU were detected in tumors in mice treated with both MVA-FCU1 and 5-FC while no detectable 5-FU was found in the circulation. This original combination between MVA and FCU1 represents a potentially safe and attractive therapeutic option to test in man.

Where do adolescents get their condoms?

PURPOSE: To determine where adolescents obtain their condoms; the availability and accessibility of condoms; condom availability in relationship to different sexually transmitted disease (STD) rates; and the availability of safer sex information in places where condoms are sold. METHODS: We conducted a random digit-dialed telephone survey of 259 14-19-year-old adolescents in Monroe County, New York. Self-reported health services use, knowledge and use of confidential services, and where adolescents obtained or intended to obtain condoms were assessed. Research assistants visited all retail establishments in five areas of similar population size with gonorrhea rates from 887 to 12,427 per 100,000 adolescents to assess how available and accessible condoms were in each store. Perceived access and actual condom availability and accessibility were compared using Chi-square and Student's t-tests. RESULTS: Trained interviewers dialed 11,800 numbers in 1993, identifying 4449 (40%) households among 11,065 numbers reached successfully. Of these, 393 (8.8%) had eligible adolescents and 259 (66%) completed interviews. Most adolescents reported obtaining, or planning to obtain, condoms in stores rather than from free health care settings. Adolescents who have used condoms more often reported having obtained them without cost than having purchased them. Condoms were available at 101 (83%) of 122 stores identified. All drug stores and 75% of supermarkets sold condoms and displayed them openly. Most small grocery stores also sold condoms (92%), but were less likely to openly display them. No stores displayed or provided safer sex information. Areas with higher STD rates had more stores (p <.01), and more stores that sold condoms (p <.01). There was no difference in condom cost by area. CONCLUSIONS: Many adolescents obtain their condoms in retail stores. Condom accessibility varied by store type and area STD rate. Increasing condom visibility in private grocery stores may increase the accessibility of condoms to adolescents in areas with highest STD rates.

Effects of rhythm regularization and rate control in improving left ventricular function in atrial fibrillation patients undergoing atrioventricular nodal ablation.

OBJECTIVES: To assess the relative contributions of rate control and rhythm regularization to left ventricular function in atrial fibrillation (AF) patients undergoing atrioventricular nodal ablation. This was performed by assessing the effect of ventricular rhythm regularization on left ventricular function during AF, and the effect of varying heart rate on left ventricular function after ablation. PATIENTS AND METHODS: Eleven patients with continuous AF and V/VI-R pacemakers undergoing therapeutic atrioventricular nodal ablation were studied. Preablation patients underwent two 30 min observation periods in a randomized, blinded fashion during which they were either in baseline AF (pacer set to default V/VI 50/min) or being paced using a rhythm stabilizing algorithm (RSA) designed to regularize rhythm without changing baseline ventricular rate. Six weeks after ablation, patients were again observed during the two following 30 min periods: pacing at a low clinically indicated rate (69+/-9 beats/min), and pacing at the rapid, mean preablation rate. During all observation periods, left ventricular function was measured continuously using a nuclear vest that provided validated measures of heart rate, ejection fraction, and normalized end-systolic volume (ESV) and end-diastolic (EDV) volume. RESULTS: Before ablation, RSA successfully regularized rhythm, decreasing the coefficient of variation of interbeat intervals 20+/-5% to 10+/-4% (P<0.001). The heart rate with RSA (105+/-19 beats/min) was not significantly different from the baseline AF rate (102+/-21 beats/min). Increased rhythm regularity achieved by RSA significantly improved left ventricular function, decreasing ESV from 62+/-12 units to 57+/-11 units (P=0.03), and increasing the ejection fraction from 31+/-11% to 36+/-11% (P=0.03). After ablation, at the clinically indicated low pacing rate of 69+/-9 beats/min, a much greater improvement in ejection fraction was observed, increasing to 44+/-13% (P=0.005 compared with preablation). However, rapid regular pacing at the mean preablation rate of 110+/-18 beats/min eradicated this improvement, decreasing the ejection fraction to 31+/-8% (P=0.003), and increasing ESV from 53+/-13 units to 62+/-8 units (P=0.006). CONCLUSIONS: Rhythm regularity achieved by a regularizing pacing algorithm can significantly, albeit modestly, improve left ventricular function in AF. However, more marked improvements in left ventricular function seen after ablation are primarily due to rate reduction alone.

Targeted macrophage cytotoxicity using a nonreplicative live vector expressing a tumor-specific single-chain variable region fragment.

Antigen-specific recognition and subsequent destruction of tumor cells is the goal of vaccine-based immunotherapy of cancer. Often, however, tumor antigen-specific cytotoxic T lymphocytes (CTLs) are either not available or in a state of anergy. In addition, MHCI expression on tumor cells is often downregulated. Either or both of these situations can allow tumor growth to proceed unchecked by CTL control. We have shown previously that tumor antigen-specific monoclonal antibodies can be expressed in vaccinia virus and that activated macrophages infected with this virus acquire the ability to kill tumor cells expressing that antigen. Here we show that a membrane-anchored form of the scFv portion of the MUC1 tumor antigen-specific monoclonal antibody, SM3, can be expressed on activated macrophages with the highly attenuated poxvirus, modified vaccinia Ankara (MVA), as a gene transfer vector. Cells infected with the MVA-scFv construct were shown to express the membrane-bound scFv by Western blot and FACS analysis. That cells expressing the membrane-anchored scFv specifically bind antigen was shown by FACS and by BIAcore analysis. GM-CSF-activated macrophages were infected with the construct and shown to recognize specifically MUC1-expressing tumor cells as measured by IL-12 release. Furthermore, activated macrophages expressing the membrane-bound scFv specifically lyse target cells expressing the MUC1 antigen but not cells that do not express MUC1.

Enveloped virus is the major virus form produced during productive infection with the modified vaccinia virus Ankara strain.

Modified vaccinia virus Ankara (MVA) is a highly attenuated virus strain that may be useful as a vaccine vector. Ultrastructural examination of purified MVA showed that most of the viral particles are enveloped in contrast to the Copenhagen strain (COP). In CsCl gradients, the majority of the MVA particles displayed a light buoyant density characteristic of the enveloped form. Consistent with these results, MVA particles were poorly labeled with antibodies against the surface of intracellular mature virus but strongly labeled with antibodies against an envelope antigen. Furthermore, MVA was more resistant than the COP strain to neutralization by mouse anti-COP antibodies. These results suggest that the MVA strain may be particularly suitable for the engineering of envelope proteins and that MVA may be able to resist the humoral immunity displayed by previously vaccinated individuals.

Transvenous pacemaker leads do not worsen tricuspid regurgitation: a prospective echocardiographic study.

Limited prospective data are available regarding the influence of pacemaker leads on tricuspid valve function. To examine the true incidence of these complications, 35 patients were prospectively examined by two-dimensional and Doppler echocardiography before and after implantation of either a permanent pacemaker or an automatic implantable cardioverter-defibrillator. Of the 35 patients imaged preoperatively, the amount of tricuspid regurgitation (TR) was judged as normal or trivial in 15 (43%), mild in 10 (29%), moderate in 8 (23%), and severe in 2 (6%). Following electrode implantation, TR was noted to be normal or trivial in 13 (38%), mild in 15 (48%), moderate in 6 (17%) and severe in 1 (3%). We conclude that implantation of permanent right ventricular electrodes is not usually associated with an acute worsening of tricuspid regurgitation in most patients.

Permanent explantation of implantable cardioverter defibrillators.

Although ICD therapy is seen as an irrevocable mode of therapy in most patients, a small number of patients do have their devices permanently explanted. The long-term outcome in these patients has not been described. The purpose of this single center study was to evaluate the long-term outcome of patients whose ICD was explanted and not replaced and to propose clinical variables that can be considered when making the decision to discontinue therapy. Ten of 323 (3.1%) patients in our ICD registry had their devices permanently explanted or turned off between 1986 and December 1998. The devices had been in place for 39 +/- 31 months preexplant. No patient had received appropriate therapy prior to surgery, which was indicated for infection or lead fracture. All patients are alive and well 75 +/- 30 months postexplant with 1 (10%) patient requiring late reimplantation. We reviewed the English language literature describing ICD explanation without replacement. A total of 151 patients were reported in eight studies and were followed for up to 30 months postexplant. Excluding patients with terminal illness or heart transplantation 57.6% survived without reimplantation. In selected patients, after not using an ICD for a long period and when clinical circumstances justify, device therapy may be discontinued with some degree of safety.

Is electrical storm in ICD patients the sign of a dying heart? Outcome of patients with clusters of ventricular tachyarrhythmias.

BACKGROUND: Electrical storm in patients with implanted cardioverter defibrillators (ICDs) is purported to carry an ominous prognosis. METHODS AND RESULTS: We retrospectively compared 40 patients with electrical storm (defined as three or more episodes of ventricular arrhythmia requiring ICD therapy in a 24 h period) with those only having isolated appropriate ICD therapy (n=57) and with patients having no or only inappropriate ICD therapy (n=125). All patients received ICDs for documented sustained VT or VF. There was no significant difference in age, sex, ejection fraction, total follow-up time, or underlying heart disease between any of the three groups. Patients who had electrical storm received their first appropriate ICD therapy 275 +/- 369 days post-implant (35% had storm as their first event) with storm occurring an average of 599 +/- 710 days post-implant. Patients had 1.5 +/- 1.0 storms in total (median= 1), with 55 +/- 91 episodes per storm. There were no significant differences in actuarial survival at 5-year follow-up between the three groups. Eighty percent of storm patients were alive 5 years post-implant. CONCLUSION: Storm is a common occurrence in ICD patients, can occur at any time during the follow-up period, and does not independently confer increased mortality.

Self-reported exercise tolerance and the risk of serious perioperative complications.

BACKGROUND: Impaired exercise tolerance during formal testing is predictive of perioperative complications. However, for most patients, formal exercise testing is not indicated, and exercise tolerance is assessed by history. OBJECTIVE: To determine the relationship between self-reported exercise tolerance and serious perioperative complications. METHODS: Our study group consisted of 600 consecutive outpatients referred to a medical consultation clinic at a tertiary care medical center for preoperative evaluation before undergoing 612 major noncardiac procedures. Patients were asked to estimate the number of blocks they could walk and flights of stairs they could climb without experiencing symptomatic limitation. Patients who could not walk 4 blocks and climb 2 flights of stairs were considered to have poor exercise tolerance. All patients were evaluated for the development of 26 serious complications that occurred during hospitalization. RESULTS: Patients reporting poor exercise tolerance had more perioperative complications (20.4% vs 10.4%; P<.001). Specifically, they had more myocardial ischemia (P = .02) and more cardiovascular (P = .04) and neurologic (P = .03) events. Poor exercise tolerance predicted risk for serious complications independent of all other patient characteristics, including age (adjusted odds ratio, 1.94; 95% confidence interval, 1.19-3.17). The likelihood of a serious complication occurring was inversely related to the number blocks that could be walked (P = .006) or flights of stairs that could be climbed (P = .01). Other patient characteristics predicting serious complications in multivariable regression analysis included history of congestive heart failure, dementia, Parkinson disease, and smoking greater than or equal to 20 pack-years. CONCLUSION: Self-reported exercise tolerance can be used to predict in-hospital perioperative risk, even when using relatively simple and familiar measures.

Validation of a noninvasive measure of local myocardial repolarization in a conscious human model: adaptation of repolarization to changes in rate.

INTRODUCTION: A commercial pacemaker sensor measure of the unipolar endocardial stimulus to T wave interval may accurately reflect changes in the monophasic action potential duration at 90% repolarization (APD90). This sensor system was used to study the kinetics of adaptation of repolarization duration to changes in heart rate in humans. METHODS AND RESULTS: Patients were studied using an external pacemaker capable of displaying all stimulus to T wave intervals for each paced beat. Right ventricular stimulation was delivered via the pacemaker and compared simultaneously to APD90. Steady-state pacing was simulated by 60 seconds of pacing at cycle lengths (CLs) 350 to 700 msec. Adaptation to a new ventricular rate was analyzed with a sudden 200-msec decrease in CL. The relation between repolarization measure and steady-state CL (n = 16) was linear with a slope of 0.16 and 0.19 for APD90 and stimulus to T wave interval, respectively (P = NS). The adaptation of both repolarization measures to a sudden change in rate were best modeled by a biexponential function. Stimulus to T wave interval exhibited a parallel course to APD90, and an analysis of normalized differences between APD90 and stimulus to T wave interval followed an approximately normal distribution, with 93.5% of the paired differences within 2 SD of the mean. CONCLUSION: A pacemaker sensor measure of stimulus to T wave interval accurately parallels APD90 during both steady-state and sudden changes in rate. Repolarization in human endocardium follows a linear relation to steady-state CL and adapts to a new rate with a biexponential function. This model represents a novel method for studying human cardiac repolarization.

Hyperaldosteronism and sudden cardiac death.

From a database of 130 implantable cardiac defibrillator recipients, 2 patients (1.5%) with sudden cardiac death as a presenting symptom, leading to diagnosis of primary hyperaldosteronism, are described. This is a newly described cause of sudden cardiac death, possibly more frequent than suspected, which should be considered in patients with malignant arrhythmias and hypokalemia.

Mechanisms of cardiopulmonary resuscitation in a patient with right ventricular dilatation--an echocardiographic contribution.

The mechanism of cardiopulmonary resuscitation is still debated. Two different theories have been proposed: direct cardiac compression versus intrathoracic pressure. A patient with dilated right cardiac chambers, who underwent a transesophageal echocardiography study during cardiopulmonary resuscitation, is reported. The direct compression mechanism was clearly demonstrated.

One-stage coronary angiography and angioplasty.

The combination of diagnostic angiography and angioplasty as a single procedure is becoming common practice in many institutions, but the feasibility and safety of this strategy have not been reported. This report describes 2,069 patients who underwent coronary angioplasty over a 3-year period at an institution where combined angiography and angioplasty is the norm. All patients were prepared before angiography for potential immediate angioplasty. In 1,719 patients, angioplasty was performed immediately after the diagnostic angiogram, while separate procedures were performed in 350 patients. Of those 350 patients, 254 were referred for angioplasty after diagnostic angiography at other hospitals. One thousand one hundred ninety-seven patients were admitted electively for treatment of stable angina pectoris, and 872 underwent procedures during hospitalization for unstable angina or acute myocardial infarction. One thousand nine hundred seven patients (92.2%) had successful angioplasties; in 130 patients (6.3%) the lesion could not be dilated, but no complication occurred, and in 32 patients (1.5%) angioplasty ended with a major complication (0.8% death, 1.0% Q-wave myocardial infarction, 0.5% emergency coronary artery bypass surgery). There was no difference between the combined and staged groups with regard to success, major and minor complication rates or in length of hospitalization after angioplasty. We conclude that routine combined strategy for angiography and angioplasty is feasible, safe, easier for the patient, and more cost-effective than 2 separate procedures.

Coronary artery-pulmonary artery fistula associated with hypertrophic cardiomyopathy.

This report describes two patients with the combination of a coronary artery fistula from the left anterior descending artery (LAD) to the pulmonary artery together with hypertrophic cardiomyopathy.