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C Schweiger

Publications and source records attributed to C Schweiger.

At least 19 recordsLinked to original sources
PubMed2005

Leukemia-derived dendritic cells can be generated from blood or bone marrow cells from patients with acute myeloid leukaemia: a methodological approach under serum-free culture conditions.

Functional dendritic cells (DC) are professional antigen-presenting cells (APC) and can be generated in vitro from healthy as well as from leukaemic cells from acute myeloid leukemia (AML) patients giving rise to APC of leukaemic origin-presenting leukaemic antigens. We describe the generation and characterization of DC from different mononuclear cell (MNC) fractions from 50 AML patients under different serum-free culture conditions, determine the optimal culture conditions and compare the results with that from 23 healthy donors. In parallel cultures, we compared DC harvests after 7- or 14-day culture, with total or adherent MNC or T-cell depleted MNC or peripheral blood (PB) or bone marrow-MNC (BM-MNC), thawn or fresh MNC, in Xvivo or CellGro serum-free media, +/-10% autologous plasma or +/-FL. In detail, we could show that AML-DC harvests were higher after 10-14 days culture (healthy DC: 7 days); total or adherent PB or BM-MNC fractions yield comparable DC counts, however, from magnetic cell sorting (MACS)-depleted MNC fractions or thawn MNC lower DC counts can be generated. Whereas the addition of FL increases the DC harvest, the addition of autologous plasma in many cases has inhibitory influence on DC maturation. CellGro and Xvivo media yield comparable DC counts. Optimal harvest of vital and mature DC from AML samples was obtained with a granulocyte/macrophage-colony stimulating factor, interleukin-4, FL and tumour necrosis factor-alpha-containing serum-free Xvivo medium after 10-14 days of culture (36/26% DC; 38/64% vital DC; 46/51% mature DC were generated from AML/healthy MNC samples). Surface marker profiles (e.g. costimulatory antigen expressing) of DC obtained from AML samples were comparable with that of healthy DC. The leukaemic derivation of AML-DC was demonstrated by the persistence of the clonal cytogenetic aberration in the DC or by coexpression of leukaemic antigens on DC. Autologous T-cell activation of leukaemia-derived DC was demonstrated in cases with AML. Autologous T cells proliferate and upregulate DC-contact-relevant antigens. We demonstrate that the generation of leukaemia-derived DC is feasable in AML under serum-free culture conditions giving rise to DC with comparable characteristics as healthy DC and offering an anti-leukaemia-directed immunotherapeutical vaccination strategy in AML.

Acute Disease↗
PubMed2005

Leukaemia-derived dendritic cells can be generated from blood or bone marrow cells from patients with myelodysplasia: a methodological approach under serum-free culture conditions.

Functional dendritic cells (DC) are professional antigen-presenting cells (APC) and can be generated in vitro from healthy as well as from leukaemic cells from AML patients giving rise to APC of leukaemic origin presenting leukaemic antigens. In a comparative methodological analysis of 50 AML samples, we could already show that leukaemia-derived DC can regularly be generated under serum-free culture conditions. In this study, we describe the generation and characterization of DC from different mononuclear cell (MNC) fractions from 24 myelodysplastic syndrome (MDS) patients under those different serum-free culture conditions, determine the optimal culture conditions and compare the results with that from 23 healthy donors. In parallel cultures, we compared DC harvests after 7- or 14-day culture, with total or adherent MNC or T-cell-depleted MNC or PB or BM-MNC, thawn or fresh MNC, in Xvivo or CellGro serum-free media, +/-10% autologous plasma or +/-FL. In detail, we could show that MDS-DC harvests compared to healthy DC were higher after 10- to 14-day culture; total or adherent PB or BM-MNC fractions yield comparable DC counts; however, from MACS-depleted MNC fractions or thawn MNC lower DC counts can be generated. Whereas the addition of FL increases the DC harvest, the addition of autologous plasma in many cases has inhibitory influence on DC maturation, CellGro and Xvivo media yield comparable DC counts. Optimal harvest of vital and mature DC from MDS samples was obtained with a GM-CSF, IL-4, FL and TNF-alpha containing serum-free Xvivo medium after 10-14 days of culture (18/26% DC; 54/64% vital DC; 59/51% mature DC were generated from MDS/healthy MNC samples). Surface marker profiles (e.g. costimulatory antigen expression) of DC obtained from MDS samples were comparable with that of healthy DC. The leukaemic derivation of MDS-DC was demonstrated by the persistence of the clonal cytogenetic aberration in the DC or by coexpression of leukaemic antigens on DC. Autologous T-cell activation of leukaemia-derived DC was demonstrated in cases with MDS. Autologous T cells proliferate and upregulate DC-contact-relevant antigens. We are the first who demonstrate that the generation of leukaemia-derived DC is feasible not only in AML but also in MDS under serum-free culture conditions giving rise to DC with comparable characteristics as healthy DC and offering an antileukaemia-directed immunotherapeutical vaccination strategy in AML and MDS.

Adult↗
PubMed2004

[Outcome of interactive training in detection and management skills for schizophrenic outpatient treatment by general practitioners].

THEORETICAL BACKGROUND: Of all outpatients with a diagnosis of schizophrenia, 30-40% refuse a psychiatrist's care. For this group of patients the general practitioner holds a key position for such different tasks as detection of prodromal schizophrenia or early warning signs of relapse and identification of risk variables for deteriorating outcome, gatekeeping (referral to specialists or other services), integration, and counseling of key relatives. Fifty percent of GPs are interested in disease-specific medical education programs. STUDY DESIGN AND METHODS: A control trial examined the changes that participating GPs intended to make in three main topics of the curriculum: (1) changing attitudes (pessimistic outcome expectation, low self-esteem), (2) enhancement of detection skills (prodromal schizophrenia, early warning signs of relapse, and risk factors for poor social and vocational integration), and (3) enhancement of management skills (dosing schemes, motivational interviewing). RESULTS: In the assessment 2 weeks after the training session, we found significant changes in favor of the trained group in detection and management skills and also improved self-confidence of GPs. CONCLUSIONS: Problem-oriented and case-based learning strategies should be preferred to lectures in training programs for psychiatric skills in primary care.

Adult↗
PubMed2001

Antioxidant vitamins and prevention of cardiovascular disease: epidemiological and clinical trial data.

Naturally occurring antioxidants such as vitamin E, beta-carotene, and vitamin C can inhibit the oxidative modification of low density lipoproteins. This action could positively influence the atherosclerotic process and, as a consequence, the progression of coronary heart disease. A wealth of experimental studies provide a sound biological rationale for the mechanisms of action of antioxidants, whereas epidemiologic studies strongly sustain the "antioxidant hypothesis." To date, however, clinical trials with beta-carotene supplements have been disappointing, and their use as a preventive intervention for cancer and coronary heart disease should be discouraged. Only scanty data from clinical trials are available for vitamin C. As to vitamin E, discrepant results have been obtained by the Alpha-Tocopherol, Beta Carotene Cancer Prevention Study with a low-dose vitamin E supplementation (50 mg/d) and the Cambridge Heart Antioxidant Study (400-800 mg/d). The results of the GISSI-Prevenzione (300 mg/d) and HOPE (400 mg/d) trials suggest the absence of relevant clinical effects of vitamin E on the risk of cardiovascular events. Currently ongoing are several large-scale clinical trials that will help in clarifying the role of vitamin E in association with other antioxidants in the prevention of atherosclerotic coronary disease.

Antioxidants↗
PubMed2001

Efficacy of n-3 polyunsaturated fatty acids after myocardial infarction: results of GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico.

Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio (GISSI)-Prevenzione was conceived as a population, pragmatic trial on patients with recent myocardial infarctions conducted in the framework of the Italian public health system. In GISSI-Prevenzione, patients were invited to follow Mediterranean dietary habits, and were treated with up-to-date preventive pharmacological interventions. Long-term n-3 PUFA (1 g daily) but not vitamin E (300 mg daily) was beneficial for death and for combined death, nonfatal myocardial infarction, and stroke. All the benefit, however, was attributable to the decrease in risk for overall, cardiovascular, cardiac, coronary, and sudden death. At variance with the orientation of a scientific scenario largely dominated by the "cholesterol-heart hypothesis," GISSI-Prevenzione results indicate n-3 PUFA (virtually devoid of any cholesterol-lowering effect) as a relevant pharmacological treatment for secondary prevention after myocardial infarction. As to the relevance and comparability of GISSI-Prevenzione results, up to 5.7 lives could be saved every 1000 patients with previous myocardial infarction treated with n-3 PUFA (1 g daily) per year. Such a result is comparable to that observed in the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial, where 5.2 lives could be saved per 1000 hypercholesterolemic, coronary heart disease patients treated with pravastatin for 1 yr. The choice of a relatively low-dose regimen (1-g capsule daily) more acceptable for long-term treatment in a population of patients following Mediterranean dietary habits, and the pattern of effects seen in GISSI-Prevenzione (namely, reduction of overall mortality with no decrease in the rate of nonfatal myocardial infarction) all strongly suggest that n-3 PUFA treatment should be considered a recommended new component of secondary prevention. The importance of this combined/additive effect is further suggested by the analyses of the interplay between diet and n-3 PUFA: There is an interesting direct correlation between size of the effect and "correctness" of background diets. It can be anticipated that a conceptual barrier must be overcome: A "dietary drug" should be added to "dietary advice," which remains fundamental to allow this statement to become true in clinical practice.

Adrenergic beta-Antagonists↗
PubMed2001

The consequences of under-use of coronary revascularization; results of a cohort study in Northern Italy.

AIM: To assess whether under-use of coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA) affects patient outcome. PATIENTS AND METHODS: A prospective observational study was performed following up a cohort of patients, candidates for a revascularization procedure (either CABG or PTCA) after an index angiogram. A total of 1258 patients, candidates -- according to explicit criteria -- for either CABG or PTCA entered the study enrolled by 16 hospitals located in a Northern Italian region (Lombardia). Information on demographic and clinical characteristics, type of care received (i.e. CABG or PTCA performed Yes/No) and vital status was obtained from revascularization laboratories, patients' hospital medical records and local census offices of the town of patients' residence. The main outcome measure was total unadjusted and adjusted mortality at a minimum follow-up of 9 months after the index cardiac angiogram. RESULTS: Patients who received CABG or PTCA (n=863) had lower mortality than those who did not (n=350) (4.8% vs 10.6%, P=0.001). This held true after adjustment for relevant risk factors between the two groups such as extent of coronary artery disease, clinical symptoms, and cardiac surgical risk index (adjusted odds ratio=0.48; 95% confidence intervals=0.30--0.77) and after performing a survival analysis (adjusted hazard ratio=0.31; 95% confidence intervals=0.19--0.50). CONCLUSIONS: Failure to perform a revascularization procedure when it was indicated led, in this study, to a significantly increased mortality showing that under-use of effective procedures may represent a significant quality of care problem even in areas where health care systems are well developed. Although the study was not specifically designed to identify determinants of under-use (i.e. reduced capacity leading to waiting lists, physicians' competence or patients' refusal to undergo a recommended procedure) our data suggest that limited capacity could have been the most important reason. Our findings also provide further evidence of the validity of the RAND method to assess the impact of under-use of coronary revascularization procedures.

Adult↗
PubMed2001

Assessment of absolute risk of death after myocardial infarction by use of multiple-risk-factor assessment equations: GISSI-Prevenzione mortality risk chart.

AIMS: To present and discuss a comprehensive and ready to use prediction model of risk of death after myocardial infarction based on the very recently concluded follow-up of the large GISSI-Prevenzione cohort and on the integrated evaluation of different categories of risk factors: those that are non-modifiable, and those related to lifestyles, co-morbidity, background, and other conventional clinical complications produced by the index myocardial infarction. METHODS: The 11-324 men and women recruited in the study within 3 months from their index myocardial infarction have been followed-up to 4 years. The following risk factors have been used in a Cox proportional hazards model: non-modifiable risk factors: age and sex; complications after myocardial infarction: indicators of left ventricular dysfunction (signs or symptoms of acute left ventricular failure during hospitalization, ejection fraction, NYHA class and extent of ventricular asynergy at echocardiography), indicators of electrical instability (number of premature ventricular beats per hour, sustained or repetitive arrhythmias during 24-h Holter monitoring), indicators of residual ischaemia (spontaneous angina pectoris after myocardial infarction, Canadian Angina Classification class, and exercise testing results); cardiovascular risk factors: smoking habits, history of diabetes mellitus and arterial hypertension, systolic and diastolic blood pressure, blood total and HDL cholesterol, triglycerides, fibrinogen, leukocytes count, intermittent claudication, and heart rate. Multiple regression modelling was assessed by receiver operating characteristic (ROC) analysis. Generalizability of the models was assessed through cross validation and bootstrapping techniques. POPULATION AND RESULTS: During the 4 years of follow-up, a total of 1071 patients died. Age and left ventricular dysfunction were the most relevant predictors of death. Because of pharmacological treatments, total blood cholesterol, triglycerides, and blood pressure values were not significantly associated with prognosis. Sex-specific prediction equations were formulated to predict risk of death according to age, simple indicators of left ventricular dysfunction, electrical instability, and residual ischaemia along with the following cardiovascular risk factors: smoking habits, history of diabetes mellitus and arterial hypertension, blood HDL cholesterol, fibrinogen, leukocyte count, intermittent claudication, and heart rate. The predictive models produced on the basis of information available in the routine conditions of clinical care after myocardial infarction provide ready to use and highly discriminant criteria to guide secondary prevention strategies. CONCLUSIONS AND IMPLICATIONS: Besides documenting what should be the preferred and practicable focus of clinical attention for today's patients, the experience of GISSI-Prevenzione suggests that periodically and prospectively collected databases on naturalistic' cohorts could be an important option for updating and verifying the impact of guidelines, which should incorporate the different components of the complex profile of cardiovascular risk. The GISSI Prevenzione risk function is a simple tool to predict risk of death and to improve clinical management of subjects with recent myocardial infarction. The use of predictive risk algorithms can favour the shift from medical logic, based on the treatment of single risk factors, to one centred on the patient as a whole as well as the tailoring of medical interventions according to patients' overall risk.

Adult↗
PubMed2001

[Glossary of terms of management and quality].

The implementation of a quality management system (QMS) in the health-care world is nowadays mandatory. This is a specific request not only of local laws but also of the World Health Organization which recently said that "By the year 2000, there should be structures and processes in all member States to ensure a continuous improvement in the quality of health care". In addition, we are bombarded by demands from patients, physicians, employers and the administration. However a QMS is something new for the medical doctor. We think that the first step to divulge the culture of quality in our field is to have a good knowledge of the specific terminology used in the QMS. This glossary explains the meaning of more than 80 terms related to the QMS.

Quality Control↗
PubMed2000

Dissociation of allergen-specific IgE and IgA responses in sera and tears of pollen-allergic patients: a study performed with purified recombinant pollen allergens.

BACKGROUND: Trees and grass pollen allergens represent potent elicitors of allergic rhinoconjunctivitis and asthma. Little is known regarding the presence of allergen-specific IgA antibodies in sera and tears and their association with IgE responses in patients with allergic conjunctivitis. OBJECTIVE: The purpose of this study was to compare the specificities of IgE and IgA antibodies in sera and tears of pollen-allergic patients with conjunctivitis by using purified recombinant pollen allergens. METHODS: Sera and tears collected from 23 pollen-allergic and from 23 nonatopic individuals were analyzed for IgE and IgA reactivity to nitrocellulose-blotted birch and timothy grass pollen extracts. In addition, we determined the specificities of IgE, IgG(1-4), and IgA antibodies with use of a panel of purified recombinant pollen allergens (timothy grass: rPhl p 1, rPhl p 2, rPhl p 5; birch: rBet v 1, rBet v 2) in serum and tear samples by immunoblotting and ELISA. Statistical analyses of data were performed by t test and Mann Whitney U test. RESULTS: Serum and tears of many of the pollen-allergic individuals with conjunctivitis exhibited specificity for the very same pollen allergens. No allergen-specific IgE antibodies were detected in tears of nonatopic individuals. IgA antibodies in sera and tears of patients with allergic conjunctivitis were mainly directed against nonallergenic moieties and showed specificities that were significantly different from those of IgE antibodies. CONCLUSION: The dissociation of IgE and IgA responses and the lack of allergen-specific IgA antibodies in mucosal secretions (eg, tears) may contribute to allergic manifestations in target organs of atopy. Induction of allergen-specific IgA antibodies may hence be considered as a promising strategy for the treatment of mucosal forms of atopy.

Allergens↗
PubMed2000

Epidemiologic study of use of resources in patients with unstable angina: the EARISA registry. On behalf on the EARISA Investigators (Epidemiologia dell'Assorbimento di Risorse nell'Ischemia, Scompenso e Angina).

AIM: The EARISA Registry was designed to describe diagnostic and therapeutic resources used in Italian cardiology centers for patients with the epidemiologically most relevant cardiac diseases. This article focuses on patients with unstable angina; characteristics associated with invasive procedures were specifically analyzed. METHODS AND RESULTS: Information was collected over a 2-week period on 1420 patients with unstable angina discharged from 308 cardiology centers. The mean length of stay was 9 +/- 6 days; 51% of patients were admitted to a coronary care unit (mean length of stay, 4 +/- 3 days). Noninvasive procedures included echocardiography (64%), Holter monitoring (25%), exercise stress testing (24%), and echocardiographic stress testing or nuclear imaging (7%). Invasive procedures were coronary angiography (39%) and percutaneous transluminal coronary angioplasty or coronary artery bypass grafting (13%). Unstable angina had a greater impact on invasive procedures than acute myocardial infarction. Variables independently associated with a higher rate of coronary angiographic procedures were younger age, higher technologic level of the hospital, and need for intravenous therapy. CONCLUSION: In Italy, approximately half the patients with unstable angina are admitted to hospitals without catheterization laboratories or cardiac surgery facilities. This fact supports the concept that treatments that can be administered in all types of hospitals are more likely to affect the outcome of patients with unstable angina. Overall, the rates of coronary angiography and revascularization procedures appeared low, and the setting where cardiologists practice, rather than patient characteristics, is the major determinant of the care given to patients with unstable angina.

Aged↗
PubMed2000

[The cardiology community and health reform. Some reflections to open a debate].

A recently introduced health care reform in Italy will modify substantially the scenario in which all physicians and also the cardiac specialists working in and out of the hospitals will operate. Therefore it is important that the cardiological community, who manages a large proportion of human and financial resources of the Italian National Health Service, knows the reform and interacts with the national and local authorities for the best implementation of the basic principles on which the reform has been founded. These principles are the following: the Italian health service will guarantee all citizens the so-called "essential levels of care" identified in accordance with four distinctive features. They must: 1) safeguard real needs of care (i.e. cosmetic surgery is not considered), 2) be evidence based, 3) be appropriate for individual patients, 4) be cost-effective. In a context of scarce resources and rapidly increasing demand of care this basic strategy seems to be the only one suitable for a National Health Service, but the application of this principle in the real world of care seems a very difficult task, and the role of medical associations is obviously crucial for a good outcome. This report illustrates some articles of the law that deal with the medical profession: guidelines and appropriateness of the criteria; accreditation, clinical competence and quality control; continuing medical education.

Cardiology↗
PubMed1999

Component-resolved diagnosis (CRD) of type I allergy with recombinant grass and tree pollen allergens by skin testing.

The diagnosis of Type I allergy is based on the measurement of allergen-specific IgE antibodies and on provocation with allergens, most frequently conducted by skin testing. Both forms of diagnosis are currently performed with allergen extracts that are difficult to standardize regarding their allergen contents, and which contain additional undefined nonallergenic components. We report the expression in Escherichia coli and purification of some of the most relevant timothy grass- and birch pollen allergens. Recombinant timothy grass- (rPhl p 1, rPhl p 2, rPhl p 5) and birch pollen (rBet v 1, rBet v 2) allergens were purified and used for the measurement of allergen-specific IgE and IgG subclass responses as well as for skin prick testing in 55 pollen allergic patients and 10 nonatopic individuals. Results obtained showed that the recombinant allergens allowed in vivo allergy diagnosis in 52 of 54 of the grass pollen and in 35 of 36 of the birch pollen allergic patients. Positive skin reactions were observed almost exclusively in patients containing detectable allergen-specific IgE antibodies but not in the nonatopic group; however, sensitivity to a given allergen as measured by skin reactivity was weakly correlated with the levels of allergen-specific IgE. Our results demonstrate that recombinant allergens can be used for component-resolved skin test diagnosis (CRD) of the patients' allergen sensitization profile, whereas allergen extracts at best allow to identify allergen-containing sources. CRD may thus represent the basis for novel forms of patient-tailored immunotherapy.

Adult↗
PubMed1999

Evaluation of four automated methods for determination of whole blood cyclosporine concentrations.

Cyclosporine is a widely used and potent immunosuppressant drug with a narrow therapeutic index. Therefore, cyclosporine concentrations should be monitored closely. Various automated immunologic methods for cyclosporine whole blood determinations are available. Two new methods, fluorescence polarization immunoassay (FPIA) for the AxSYM by Abbott Laboratories, Chicago, IL, and the cloned enzyme donor immunoassay (CEDIA) by Boehringer Mannheim, Mannheim, Germany, have been introduced. In addition, Dade Behring improved its enzyme multiplied immunoassay (EMIT) assay. The present study evaluated all 3 new methods in comparison with high-performance liquid chromatography (HPLC) and the FPIA for the TDx analyzer. We measured whole blood cyclosporine concentrations of 179 samples obtained from 127 patients after kidney, bone marrow, heart-lung, and liver transplantation. All 4 automated immunologic methods can be used for routine measurement of cyclosporine whole blood concentrations. Disadvantages, such as higher cross-reactivity (Abbott TDx, CEDIA) or a limited linearity range (EMIT), are accompanied by advantages, such as a high precision (Abbott TDx) or an easy sample handling procedure (CEDIA). Information presented in this article should help to find the most adequate cyclosporine method for each medical laboratory.

Antibodies, Monoclonal↗
PubMed1999

[One medicine].

Explore the source record for details and available documents.

Cardiology↗