Prominin-1+/CD133+ bone marrow-derived heart-resident cells suppress experimental autoimmune myocarditis.

AIMS: Experimental autoimmune myocarditis (EAM) is a CD4(+) T cell-mediated mouse model of inflammatory heart disease. Tissue-resident bone marrow-derived cells adopt different cellular phenotypes depending on the local milieu. We expanded a specific population of bone marrow-derived prominin-1-expressing progenitor cells (PPC) from healthy heart tissue, analysed their plasticity, and evaluated their capacity to protect mice from EAM and heart failure. METHODS AND RESULTS: PPC were expanded from healthy mouse hearts. Analysis of CD45.1/CD45.2 chimera mice confirmed bone marrow origin of PPC. Depending on in vitro culture conditions, PPC differentiated into macrophages, dendritic cells, or cardiomyocyte-like cells. In vivo, PPC acquired a cardiac phenotype after direct injection into healthy hearts. Intravenous injection of PPC into myosin alpha heavy chain/complete Freund's adjuvant (MyHC-alpha/CFA)-immunized BALB/c mice resulted in heart-specific homing and differentiation into the macrophage phenotype. Histology revealed reduced severity scores for PPC-treated mice compared with control animals [treated with phosphate-buffered saline (PBS) or crude bone marrow at day 21 after MyHC-alpha/CFA immunization]. Echocardiography showed preserved fractional shortening and velocity of circumferential shortening in PPC but not PBS-treated MyHC-alpha/CFA-immunized mice. In vitro and in vivo data suggested that interferon-gamma signalling on PPC was critical for nitric oxide-mediated suppression of heart-specific CD4(+) T cells. Accordingly, PPC from interferon-gamma receptor-deficient mice failed to protect MyHC-alpha/CFA-immunized mice from EAM. CONCLUSION: Prominin-1-expressing, heart-resident, bone marrow-derived cells combine high plasticity, T cell-suppressing capacity, and anti-inflammatory in vivo effects.

Appropriateness of antibiotic treatment in intravenous drug users, a retrospective analysis.

BACKGROUND: Infectious disease is often the reason for intravenous drug users being seen in a clinical setting. The objective of this study was to evaluate the appropriateness of treatment and outcomes for this patient population in a hospital setting. METHODS: Retrospective study of all intravenous drug users hospitalized for treatment of infectious diseases and seen by infectious diseases specialists 1/2001-12/2006 at a university hospital. Treatment was administered according to guidelines when possible or to alternative treatment program in case of patients for whom adherence to standard protocols was not possible. Outcomes were defined with respect to appropriateness of treatment, hospital readmission, relapse and mortality rates. For statistical analysis adjustment for multiple hospitalizations of individual patients was made by using a generalized estimating equation. RESULTS: The total number of hospitalizations for infectious diseases was 344 among 216 intravenous drug users. Skin and soft tissue infections (n = 129, 37.5% of hospitalizations), pneumonia (n = 75, 21.8%) and endocarditis (n = 54, 15.7%) were most prevalent. Multiple infections were present in 25%. Treatment was according to standard guidelines for 78.5%, according to an alternative recommended program for 11.3%, and not according to guidelines or by the infectious diseases specialist advice for 10.2% of hospitalizations. Psychiatric disorders had a significant negative impact on compliance (compliance problems in 19.8% of hospitalizations) in multiple logistic regression analysis (OR = 2.4, CI 1.1-5.1, p = 0.03). The overall readmission rate and relapse rate within 30 days was 13.7% and 3.8%, respectively. Both non-compliant patient behavior (OR = 3.7, CI 1.3-10.8, p = 0.02) and non-adherence to treatment guidelines (OR = 3.3, CI 1.1-9.7, p = 0.03) were associated with a significant increase in the relapse rate in univariate analysis. In 590 person-years of follow-up, 24.6% of the patients died: 6.4% died during hospitalization (1.2% infection-related) and 13.6% of patients died after discharge. CONCLUSION: Appropriate antibiotic therapy according to standard guidelines in hospitalized intravenous drug users is generally practicable and successful. In a minority alternative treatments may be indicated, although associated with a higher risk of relapse.

CD11b+ monocytes abrogate Th17 CD4+ T cell-mediated experimental autoimmune myocarditis.

Experimental autoimmune myocarditis (EAM) represents a Th17 T cell-mediated mouse model of postinflammatory heart disease. In BALB/c wild-type mice, EAM is a self-limiting disease, peaking 21 days after alpha-myosin H chain peptide (MyHC-alpha)/CFA immunization and largely resolving thereafter. In IFN-gammaR(-/-) mice, however, EAM is exacerbated and shows a chronic progressive disease course. We found that this progressive disease course paralleled persistently elevated IL-17 release from T cells infiltrating the hearts of IFN-gammaR(-/-) mice 30 days after immunization. In fact, IL-17 promoted the recruitment of CD11b(+) monocytes, the major heart-infiltrating cells in EAM. In turn, CD11b(+) monocytes suppressed MyHC-alpha-specific Th17 T cell responses IFN-gamma-dependently in vitro. In vivo, injection of IFN-gammaR(+/+)CD11b(+), but not IFN-gammaR(-/-)CD11b(+), monocytes, suppressed MyHC-alpha-specific T cells, and abrogated the progressive disease course in IFN-gammaR(-/-) mice. Finally, coinjection of MyHC-alpha-specific, but not OVA-transgenic, IFN-gamma-releasing CD4(+) Th1 T cell lines, together with MyHC-alpha-specific Th17 T cells protected RAG2(-/-) mice from EAM. In conclusion, CD11b(+) monocytes play a dual role in EAM: as a major cellular substrate of IL-17-induced inflammation and as mediators of an IFN-gamma-dependent negative feedback loop confining disease progression.

Reliability and validity of a German asthma quality of life questionnaire.

The Asthma Quality of Life Questionnaire (University of Sydney [AQLQ-Sydney]) is a self-administered questionnaire that has been developed in Australia and validated in different languages in Australia, the USA and Spain. We developed a German translation of this questionnaire by applying a sequential forward and backward translation approach. The objective of this study was to validate a German translation of the AQLQ-Sydney questionnaire in an outpatient population of asthmatic patients in Switzerland. Outpatients were assessed for a diagnosis of asthma and those who consented were selected for the validation study. All patients had spirometry, methacholine challenge testing, fractional exhaled nitric oxide recorded and answered the German AQLQ-Sydney. A subgroup of 17 patients answered the questionnaire for a second time after receiving asthma treatment with combined steroids and bronchodilators for two months. Test-retest-reliability was tested in 12 stable asthmatic patients without treatment modification. Of 90 patients assessed, 57 were diagnosed with asthma and participated in the validation study. The total score did not significantly correlate with any of the objective measures of severity of asthma. However, the "Breathlessness" subscale score correlated weakly with PD20 methacholine. Internal consistency was high with Cronbach's alpha of 0.97 for the total score and 0.91-0.97 for the subscale scores. Test-retest reliability was also high for the total score and the subscale scores. The questionnaire detected a significant improvement in total quality of life score and "Breathlessness" and "Mood" subscale scores after a period of combined treatment with inhaled steroids and long acting bronchodilators. The German translation of the AQLQ-Sydney had a good internal consistency and test-retest-reliability in stable asthmatic patients. It shows responsiveness to treatment. Some correlations with objective markers were detected.

High prevalence of newly detected hypertension in hospitalized patients: the value of inhospital 24-h blood pressure measurement.

OBJECTIVE: Screening for hypertension in hospitalized patients could reduce the number of individuals with unrecognized hypertension. We hypothesized that 24-h blood pressure monitoring is an adequate tool to detect unrecognized hypertension among inpatients. METHODS: Clinically stable inpatients in the Department of Internal Medicine, Department of Visceral Surgery and Department of Orthopaedics were included in the cross-sectional study. Every patient underwent inhospital 24-h blood pressure measurement. Previously unknown hypertension was defined as 24-h blood pressure of at least 125/80 mmHg in the absence of known hypertension. Forty-two patients had an additional 24-h blood pressure measurement after discharge, to compare mean inhospital and outpatient 24-h blood pressure values. RESULTS: In 314 consecutive inpatients, 24-h blood pressure measurement was performed. Among 139 patients without known hypertension, 53 were hypertensive. The mean routine and 24-h blood pressures in these patients were 135/77 and 137/82 mmHg, respectively. Thirty-seven of these patients had normal routine blood pressure and could be detected only by 24-h blood pressure measurement. Patients with unknown hypertension had a marked cardiovascular risk profile, 26 being at high or very high cardiovascular risk. However, documented cardiovascular disease was present in only seven patients, suggesting that effective treatment could prevent a considerable number of cardiovascular events. The agreement between inhospital and outpatient 24-h blood pressure measurement in 42 patients was good. CONCLUSIONS: By performing inhospital 24-h blood pressure measurement, a considerable number of patients with previously unknown hypertension can be detected.

Routine blood pressure measurements do not predict adverse events in hospitalized patients.

PURPOSE: Countless blood pressure measurements are performed every day for almost every hospitalized patient. We analyzed the value of routine blood pressure measurements on patient care in an unselected group of hospitalized patients. METHODS: The study included 639 patients who were admitted to the hospital with a broad range of medical conditions. Two independent investigators reviewed the medical charts of the patients. Routine blood pressure values were abstracted from the patient charts and evaluated with respect to the occurrence of adverse clinical events in the study group. Changes in blood pressure between the last measurement just before adverse clinical events and the mean blood pressure values 72 hours before the adverse events were calculated and compared with mean normal day-to-day variations in blood pressure. RESULTS: In every patient, a mean of 1.6 +/- 0.6 routine blood pressure measurements per day were performed. Of the 639 patients in the study, 122 (19%) had clinical complications. The most commonly occurring complications were gastrointestinal bleeding (n = 15), falls (n = 13), other bleeding (n = 12) and pneumonia (n = 8). In patients who experienced clinical complications, pre-event systolic and diastolic blood pressure changes of at least 10 mm Hg occurred in 41% and 24% of the group, respectively, but this was not different from the normal day-to-day variations observed in patients who had no clinical complications. The results also were similar for patients who died or who had a severe adverse event that required admission to an intensive care unit. CONCLUSION: Routine blood pressure measurements in a general hospital patient population do not predict clinical adverse events.

Can airway obstruction be estimated by lung auscultation in an emergency room setting?

OBJECTIVE: Lung auscultation is a central part of the physical examination at hospital admission. In this study, the physicians' estimation of airway obstruction by auscultation was determined and compared with the degree of airway obstruction as measured by FEV(1)/FVC values. METHODS: Two hundred and thirty-three patients consecutively admitted to the medical emergency room with chest problems were included. After taking their history, patients were auscultated by an Internal Medicine registrar. The degree of airway obstruction had to be estimated (0=no, 1=mild, 2=moderate and 3=severe obstructed) and then spirometry was performed. Airway obstruction was defined as a ratio of FEV(1)/FVC <70%. The degree of airway obstruction was defined on FEV(1)/FVC as mild (FEV(1)/FVC <70% and >50%), moderate (FEV(1)/FVC <50% >30%) and severe (FEV(1)/FVC <30%). RESULTS: One hundred and thirty-five patients (57.9%) had no sign of airway obstruction (FEV(1)/FVC >70%). Spirometry showed a mild obstruction in 51 patients (21.9%), a moderate obstruction in 27 patients (11.6%) and a severe obstruction in 20 patients (8.6%). There was a weak but significant correlation between FEV(1)/FVC and the auscultation-based estimation of airway obstruction in Internal Medicine Registrars (Spearman's rho=0.328; P<0.001). The sensitivity to detect airway obstruction by lung auscultation was 72.6% and the specificity only 46.3%. Thus, the negative predictive value was 68% and the positive predictive value 51%. In 27 patients (9.7%), airway obstruction was missed by lung auscultation. In these 27 cases, the severity of airway obstruction was mild in 20 patients, moderate in 5 patients and severe in 2 patients. In 82 patients (29.4%) with no sign of airway obstruction (FEV(1)/FVC >70%), airway obstruction was wrongly estimated as mild in 42 patients, as moderate in 34 patients and as severe in 6 patients, respectively. By performing multiple logistic regression, normal lung auscultation was a significant and independent predictor for not having an airway obstruction (OR 2.48 (1.43-4.28); P=0.001). CONCLUSION: Under emergency room conditions, physicians can quite accurately exclude airway obstruction by auscultation. Normal lung auscultation is an independent predictor for not having an airway obstruction. However, airway obstruction is often overestimated by auscultation; thus, spirometry should be performed.

Diagnostic value of lung auscultation in an emergency room setting.

BACKGROUND: In daily routine, physicians use history, physical examination and technology-based information such as laboratory tests and imaging studies to diagnose the patients' disease. We determined the diagnostic value of lung auscultation in patients admitted to the Medical emergency room with chest symptoms. METHODS: Two-hundred-and forty-three consecutive patients (137 males), mean age 59.2 years were included. Internal Medicine registrars had to make a presumptive diagnosis, 1) after having taken the history and 2) after having auscultated the lungs. Thereafter, routine diagnostic procedures were performed. The estimated diagnosis was compared with the final diagnosis based on the written report to the Family Practitioner. RESULTS: Two-hundred-eighty-seven diagnoses were made. Eighteen percent of patients suffered from left heart failure, 13% from unexplained chest pain, 10.5% from chest wall pain, and 10.5% from pneumonia. Forty-one percent of the diagnoses were already correct when based only on the patient's history. Lung auscultation improved the diagnostic yield only in 1% and worsened it in another 3%. By multiple logistic regression, normal lung auscultation (OR 0.12 [95CI% 0.053-0.29]) was the independent predictor for not having a lung or heart disease. However, elevation of B-type natiuretic peptide (BNP) (OR 1.16 per 100 pg/ml (95CI% 1.004-1.35), wheezing (OR 0.023 [0.002-0.33]) and pCO2 (OR 0.25 (0.10-0.621) were independent predictors for having a heart disease, whereas wheezing (OR 7.41 [3.26-16.83]) and CRP (OR 1.008 per 10 units [1.003-1.014]) were risk factors for having a lung disease. CONCLUSION: In contrast to history taking, abnormal lung auscultation does not appear to contribute considerably to the final diagnosis in patients presenting with chest symptoms in an emergency room setting. However, normal lung auscultation is a valuable predictor for not having a lung or heart disease, whereas wheezing is a predictor for having a lung disease and not having a heart disease.

Effect of different antilipidemic agents and diets on mortality: a systematic review.

BACKGROUND: Guidelines for the prevention and treatment of hyperlipidemia are often based on trials using combined clinical end points. Mortality data are the most reliable data to assess efficacy of interventions. We aimed to assess efficacy and safety of different lipid-lowering interventions based on mortality data. METHODS: We conducted a systematic search of randomized controlled trials published up to June 2003, comparing any lipid-lowering intervention with placebo or usual diet with respect to mortality. Outcome measures were mortality from all, cardiac, and noncardiovascular causes. RESULTS: A total of 97 studies met eligibility criteria, with 137,140 individuals in intervention and 138,976 individuals in control groups. Compared with control groups, risk ratios for overall mortality were 0.87 for statins (95% confidence interval [CI], 0.81-0.94), 1.00 for fibrates (95% CI, 0.91-1.11), 0.84 for resins (95% CI, 0.66-1.08), 0.96 for niacin (95% CI, 0.86-1.08), 0.77 for n-3 fatty acids (95% CI, 0.63-0.94), and 0.97 for diet (95% CI, 0.91-1.04). Compared with control groups, risk ratios for cardiac mortality indicated benefit from statins (0.78; 95% CI, 0.72-0.84), resins (0.70; 95% CI, 0.50-0.99) and n-3 fatty acids (0.68; 95% CI, 0.52-0.90). Risk ratios for noncardiovascular mortality of any intervention indicated no association when compared with control groups, with the exception of fibrates (risk ratio, 1.13; 95% CI, 1.01-1.27). CONCLUSIONS: Statins and n-3 fatty acids are the most favorable lipid-lowering interventions with reduced risks of overall and cardiac mortality. Any potential reduction in cardiac mortality from fibrates is offset by an increased risk of death from noncardiovascular causes.

Initial clinical evaluation of cardiac systolic murmurs in the ED by noncardiologists.

It is not exactly known how ED physicians perform in evaluating cardiac systolic murmurs. In 203 consecutive medical ED patients with systolic murmur, we compared the initial clinical evaluation, including auscultation, with transthoracic echocardiography. Of the 203 patients, 132 (65%) had innocent murmurs and 71 patients (35%) had valvular heart disease. Sensitivity and specificity of the initial clinical routine evaluation in diagnosing echocardiographic valvular heart disease were 82% (70%-86%) and 69% (60%-76%), respectively. Independent significant positive predictors of valvular heart disease were grade >2/6 systolic murmur (odds ratio [OR], 8.3; confidence interval [CI], 3.5-19.7, P<.001) and pathologic electrocardiogram (ECG) (OR, 8.4; CI, 3.2-22, P<.001. Patients younger than 50 years with a systolic murmur graded < or =2/6 had innocent murmurs in 98%. The initial clinical evaluation, including auscultation, by experienced ED physicians in internal medicine distinguishes well between innocent murmurs and valvular heart disease in medical patients with cardiac systolic murmurs.

Clinical outcomes of stents versus balloon angioplasty in non-acute coronary artery disease. A meta-analysis of randomized controlled trials.

AIMS: To evaluate whether stents as compared to balloon angioplasty reduce mortality in patients with non-acute coronary artery disease. METHODS AND RESULTS: We identified randomized controlled trials comparing stents to balloon angioplasty for the treatment of non-acute coronary artery disease by searching major medical databases from 1979 to March 2002. Two independent reviewers selected and extracted data from trials that had to report data on death and myocardial infarction. Nineteen trials, with a total of 8004 patients, fulfilled our inclusion criteria. For 1000 patients treated with stents rather than balloon angioplasty, 3 (95% CI 0-6), 5 (95% CI 0-9), and 6 (95% CI -1-12) additional lives were saved at 30 days, 6 and 12 months. At 12 months, for 1000 patients treated with stents rather than balloon angioplasty 46 (95% CI 25-66) additional target vessel revascularizations were avoided, but 25 (95% CI 15-34) additional bleeding complications with need for blood transfusion or surgical intervention occurred. In sensitivity analysis 11 (95% CI 2-20) and 2 (95% CI -4-7) deaths were avoided per 1000 patients treated with stents rather than PTCA in trials that routinely used compared to trials that did not use glycoprotein IIb/IIIa inhibitors. CONCLUSION: In non-acute coronary disease stents may reduce overall mortality, but this benefit seems to be limited to stents used in conjunction with glycoprotein IIb/IIIa inhibitors. Stents compared to PTCA reduce target vessel revascularizations, but increase the risk of bleeding complications.