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  • Bone marrow transplantation  (8)
  • CORONARY-HEART-DISEASE  (2)
  • 1
    Keywords: MODEL ; COHORT ; cohort study ; EPIDEMIOLOGY ; RISK ; RISK-FACTORS ; diabetes ; ATHEROSCLEROSIS ; C-REACTIVE PROTEIN ; inflammation ; CORONARY-HEART-DISEASE ; INTERLEUKIN-6 ; myocardial infarction ; CARDIOVASCULAR EVENTS
    Abstract: Objectives: Circulating interleukin-6 (IL-6) is increased in diabetes patients who are in general also at greater cardiovascular risk. Thus, we investigated whether IL-6 is associated with incident primary cardiovascular events and improves risk prediction in diabetes patients. Methods: Serum IL-6 levels were measured at baseline in 1072 diabetic participants of the ESTHER study. During 5 years of follow-up, 84 experienced a primary cardiovascular event (myocardial infarction, stroke, cardiovascular death). Hazard ratios (HR) and 95% confidence intervals (95% CI), measures of model discrimination and calibration were calculated. Results: High IL-6 levels were associated with increased event risk (adjusted HR 1.90 [95% CI 1.06-3.40] for top versus bottom tertile; p = 0.011). The addition of IL-6 to models containing Framingham score variables did not substantially improve prediction. Conclusions: Although serum IL-6 was significantly associated with cardiovascular risk, it did not substantially improve risk prediction above traditional risk factors in a diabetic cohort.
    Type of Publication: Journal article published
    PubMed ID: 21334625
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  • 2
    Keywords: MORTALITY ; MEN ; C-REACTIVE PROTEIN ; CORONARY-HEART-DISEASE ; PREDICTOR ; SERUM ADIPONECTIN ; INTERLEUKIN-18 ; CHRONIC KIDNEY-DISEASE ; AUGSBURG CASE-COHORT ; MONICA/KORA AUGSBURG
    Abstract: OBJECTIVE-Inflammatory processes contribute to both diabetes and cardiovascular risk. We wanted to investigate whether circulating concentrations of proinflammatory immune mediators and adiponectin in diabetic patients are associated with incident cardiovascular events. RESEARCH DESIGN AND METHODS-In 1,038 participants with diabetes of the population-based ESTHER study, of whom 326 showed signs of renal dysfunction, Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for the association of increasing concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), IL-18, macrophage migration inhibitory factor (MIF), adiponectin, and leptin with cardiovascular events (myocardial infarction, stroke, or fatal cardiovascular event) during a follow-up period of 8 years. RESULTS-During follow-up, 161 subjects with diabetes experienced a primary cardiovascular event. Proinflammatory markers were not associated with a higher risk for primary cardiovascular events in the total study population after adjustment for multiple confounders. However, IL-6 and MIF were associated with cardiovascular events in subjects with renal dysfunction (HR for the comparison of top vs. bottom tertile 1.98 [95% CI 1.12-3.52], P [trend] = 0.10 for IL-6; 1.48 [0.87-2.51], P [trend] = 0.04 for MIF). Adiponectm levels were associated with cardiovascular events in the total population (1.48 [1.01-2.21], P [trend] = 0.03), and the association was even more pronounced in the subgroup with renal dysfunction (1.97 [1.08-3.57], P [trend] = 0.02). CONCLUSIONS-In particular, the absence of an association between CRP and a U-shaped association of adiponectin levels with incident cardiovascular events show that associations between circulating immune mediators and cardiovascular risk differ between diabetic patients and subjects of the general population.
    Type of Publication: Journal article published
    PubMed ID: 23378623
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  • 3
    ISSN: 1432-0584
    Keywords: Complement system ; C1 inhibitor ; Bone marrow transplantation ; Capillary leak syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Capillary leak syndrome (CLS) is a severe complication after bone marrow transplantation (BMT). To investigate whether there is a pathogenetic role of the complement system, we monitored the levels of the terminal complement complex C5b-9 (TCC) and C3a-desArg as indicators of an activation of the complement system and the inhibitor of the classical pathway of the complement cascade, C1 inhibitor (C1-INH), in 48 bone marrow transplant recipients from 1 week before to 5 weeks after transplantation. Capillary leak syndrome developed in 7 out of 48 patients between days 1 and 12 after BMT. Complement activation as indicated by TCC levels was more pronounced in patients with CLS (n=7) from day −8 to +28 (p〈0.05; day −1) and the elevation of TCC levels lasted longer in CLS patients (peak day 21) than in patients without this complication (peak day 7). Mean C3a-desArg levels were highest in patients with CLS reaching a peak at day 7. During the early posttransplant period a significant elevation of C1-INH levels (p〈0.01 and p〈0.05 respectively) compared with baseline levels (day −8) was found in patients with and without CLS, which was more pronounced in those patients with CLS (p〈0.05). Although we could not observe an absolute C1-INH deficiency as compared to healthy individuals our data support the presence of a relative deficiency of the inhibitor which might explain the reported beneficial effects of C1-INH substitution in BMT related CLS.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0584
    Keywords: Knochenmarktransplantation ; Vermeidung von GvH ; T-Zell-Globulin ; Bone marrow transplantation ; Prevention of GvH ; Preincubation of donor bone marrow ; Specific anti-T-cell globulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary An in vitro incubation of incompatible donor bone marrow by xenogenic anti-T-cell globulin (ATG) suppressed an otherwise lethal GvH reaction in animal models. An application of this principle to clinical bone marrow transplantation was successfully tried in three patients with acute lymphoblastic leukemia. Preparation of the specific anti-human T-cell globulin (ATCG-H) was carried out by absorption of anti-human thymocyte globulin with liver-kidney homogenate, chronic lymphocytic leukemia cells of B-cell type, and erythrocytes. Subsequent testing revealed that the serum still reacted with human T-cells but no longer reduced the number of colony-forming units in culture (CFU-C). All three bone marrow recipients were treated by chemotherapeutic conditioning and total body irradiation followed by grafting of in vitro treated bone marrow from HLA-identical siblings. The transplantation of the bone marrow was well tolerated and no major side effects were encountered. No patient so far (24, 7, 6 months) has shown any signs of GvHD. The in vitro pretransplantation treatment of bone marrow with anti T-globulin may be a new approach to the prevention for GvHD in man.
    Notes: Zusammenfassung Tierexperimentelle Befunde ergaben den Hinweis, daß bei Knochenmarktransplantation mit inkompatiblem Spendermark eine Vorinkubation des Spendermarkes mit xenogenem Anti-T-Zell-Globulin eine sonst toxisch verlaufende Graft versus Host-(GvH)Erkrankung vermeidet. Bei drei Patienten mit akuter lymphatischer Leukämie wurde dieses Prinzip bei der Knochenmarktransplantation erfolgreich klinisch angewandt. Zur Anwendung gelangte ein spezifisches antihumanes Anti-T-Zell-Globulin (ATCG-H), das durch mehrere Absorptionsschritte aus rohem antihumanem Globulin (ATG) gewonnen wurde. Eine Vortestung des Serums ergab eine unveränderte Reaktion gegen menschliche T-Zell-Lymphozyten ohne toxische Nebenwirkungen auf in vitro nachweisbare Vorläuferzellen der Hämopoese (CFU-C). Die Knochenmarktransplantation wurde bei allen drei Patienten nach üblicher Chemotherapie („Konditionierung“) und Ganzkörperbestrahlung mittels vorinkubiertem Spendermark von HLA-identischen Geschwisterndurchgeführt. Toxische Nebenwirkungen durch die Vorinkubation traten nicht auf. Anzeichen einer GvH wurden bisher (24, 7, 6 Monate) bei den Empfängern nicht beobachtet. Die in vitro -Vorinkubation von Spenderknochenmark kann somit als ungefährlicher neuer Versuch zur Vermeidung einer GvH beim Menschen empfohlen werden.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0584
    Keywords: Acute leukemia ; Bone marrow transplantation ; Anti-T-cell-globulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Anti-human-thymocyte globulin (AHTZG) was applied to prevent GvHD in clinical bone marrow transplantation. AHTZG produced by absorption with several cell preparations reacted specifically with T-lymphocyte populations and was no longer inhibitory to human CFUc and bone marrow growth in diffusion chambers. Marrow grafts of 14 patients with ALL were incubated in vitro with AHTZG and transferred to the recipients conditioned with antileukemic chemotherapy and total body irradiation of 1000 rad. Ten patients were transplanted after relaps, four patients during remission. The patients tolerated the marrow without side effects and a hemopoietic engraftment was seen in 12 cases. Three patients showed signs of GvHD on the skin, two of them showed later on also manifestations in the liver. In the other cases no GvHD could be detected. Five out of 14 patients are still alive between 144 and 964 days post transplantation in remission.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0584
    Keywords: Biopterin ; Bone marrow transplantation ; Hemopoiesis ; Reticulocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Bone marrow aplasia was induced by fractionated whole body irradiation with 3000 R and restitution was started by autologous bone marrow transplantation. During the period of aplasia the amount of buffy coat biopterin clearly followed the decline of leukocytes and, vice versa, during reconstitution it largely paralleled their increase in number. The amount of red cell biopterin closely correlated with the number of reticulocytes rather than with the fairly constant values for hematocrit or of erythrocytic protein. Thereby it clearly followed the various periods of red cell recovery. The amount of cellular biopterin, its concentration with respect to cell number or to unit of protein and the percentage distribution of biopterin among the cell fractions are presented as characteristics of the activity of hemopoietic cell proliferation.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0584
    Keywords: Chronic myeloid leukemia ; Interferon ; Hydroxyurea ; Busulfan ; Bone marrow transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The therapeutic efficacy of interferon-alpha (IFN-α) in the treatment of chronic myeloid leukemia is currently being tested in a number of institutional, interinstitutional, and international trials. There is no doubt that responses are achieved in many patients, and in a small subset complete eradication of clonogenic cells may be possible. However, it has not yet been shown that overall survival of patients treated with IFN-α is better than that of those treated with conventional cytoreductive drugs. There are still controversial opinions on problems such as dosages and duration of treatment, combination with cytostatic agents, definition of responses, and relevance of cytogenic and molecular data. An international workshop discussed the data on interferon therapy and attempted to define the role of interferon today in the management of chronic myeloid leukemia.
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  • 8
    ISSN: 1432-0584
    Keywords: Key words Complement system ; C1 inhibitor ; Bone marrow transplantation ; Capillary leak syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Capillary leak syndrome (CLS) is a severe complication after bone marrow transplantation (BMT). To investigate whether there is a pathogenetic role of the complement system, we monitored the levels of the terminal complement complex C5b-9 (TCC) and C3a-desArg as indicators of an activation of the complement system and the inhibitor of the classical pathway of the complement cascade, C1 inhibitor (C1-INH), in 48 bone marrow transplant recipients from 1 week before to 5 weeks after transplantation. Capillary leak syndrome developed in 7 out of 48 patients between days 1 and 12 after BMT. Complement activation as indicated by TCC levels was more pronounced in patients with CLS (n = 7) from day –8 to +28 (p〈0.05; day –1) and the elevation of TCC levels lasted longer in CLS patients (peak day 21) than in patients without this complication (peak day 7). Mean C3a-desArg levels were highest in patients with CLS reaching a peak at day 7. During the early posttransplant period a significant elevation of C1-INH levels (p〈0.01 and p〈0.05 respectively) compared with baseline levels (day –8) was found in patients with and without CLS, which was more pronounced in those patients with CLS (p〈0.05). Although we could not observe an absolute C1-INH deficiency as compared to healthy individuals our data support the presence of a relative deficiency of the inhibitor which might explain the reported beneficial effects of C1-INH substitution in BMT related CLS.
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  • 9
    ISSN: 1432-1440
    Keywords: Bone marrow transplantation ; Acute leukaemia ; Knochenmarktransplantation ; akute Leukämie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Im Rahmen der Arbeitsgemeinschaft Knochenmarktransplantation München wurden von August 1975 bis Juni 1980 insgesamt 17 Patienten mit rezidivierter, akuter Leukämie mit Knochenmark von HLA-identischen Geschwistern transplantiert. Die antileukämische und immunsuppressive Vorbehandlung bestand aus BCNU, Cytosin-Arabinosid, Cyclophosphamid in hoher Dosierung und Ganzkörperbestrahlung mit etwa 9 Gy Körpermitteldosis an einer60Co-Doppelbestrahlungsanlage. Die Prophylaxe einer Graft-versus-Host Krankheit (GvHK) wurde in allen Fällen mit Methotrexat durchgeführt, bei neun Patienten wurde als zusätzliche GvHK-Prophylaxe das Knochenmark mit Anti-T-Zell-Globulin inkubiert, von dem die Antikörper gegen hämopoetische Stammzellen absorbiert waren. Zwei von fünf auswertbaren Patienten, die unbehandeltes Knochenmark erhalten hatten, entwickelten chronische GvHK, während kein Patient nach ATCG-Inkubation des Knochenmarkes eindeutige GvH-Krankheit bekam. Sechs Patienten leben in Vollremission zwischen einem und 33 Monaten nach Knochenmarktransplantation (KMT). Fünf Patienten starben mit Rezidiven zwischen 3 1/2 und 24 Monaten nach KMT, drei Patienten mit interstitieller Pneumonie innerhalb von 3 Monaten nach KMT und drei Patienten innerhalb von 4 Wochen ohne ausreichende Knochenmarkfunktion. Vier von 13 Patienten, die vor mehr als 6 Monaten transplantiert wurden, überleben zur Zeit 11, 14, 19 und 33 Monate in Vollremission. Unsere Ergebnisse bestätigen, daß selbst in fortgeschrittenen Stadien akuter Leukämie durch KMT noch langfristige Remissionen erreichbar sind.
    Notes: Summary Seventeen patients with relapsed, acute leukemia were grafted with bone marrow from HLA-identical siblings by the ‘Munich Cooperative Group for Bone Marrow Transplantation’ during the period from August 1975 to June 1980. The antileukemic and immunosuppressive conditioning treatment consisted of high doses of Bischlorethyl nitrosourea, Cytosine-Arabinoside and Cyclophosphamide, as well as, total body irradiation of about 9 Gy (midline body dose) from dual60Cobalt sources. Methotrexate was given to all patients for prophylaxis of graft-versus-host disease (GvHD). Nine patients received marrow that was treated with anti-T-cell globulin (ATCG) “in vitro”. — Crossreacting antibodies against hemopoietic stem cells were removed by absorption. Two of 5 evaluable patients given untreated marrow developed chronic GvHD, while patients given ATCG-treated marrow did not show unequivocal symptoms of GvHD. Six patients are in complete remission one to 33 months following bone marrow transplantation (b.m.t.) Five patients died with relapses of leukemia between 3 1/2 and 24 months following b.m.t., 3 patients died with interstitial pneumonia within 3 months of b.m.t. and 3 patients died with insufficient graft function within 4 weeks of b.m.t. Four of thirteen patients that were grafted more than 6 months ago are presently alive and in continuous complete remission at 11, 14, 29 and 33 months following b.m.t. Our results confirm that longterm remissions can be obtained with b.m.t. in patients with acute leukemia in advanced stage.
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  • 10
    ISSN: 1432-1440
    Keywords: Bone marrow transplantation ; Aplastic anaemia ; Knochenmarktransplantation ; Aplastische Anämie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Im Rahmen der Arbeitsgemeinschaft Knochenmarktransplantation — München (AG-KMT) wurden vom März 1975 bis Mai 1980 insgesamt 12 Patienten wegen schwerer, aplastischer Anämie mit Knochenmarktransplantation (KMT) behandelt. Sechs Patienten überleben derzeit mit normalem Blutbild und Knochenmark zwischen 10 Monaten und mehr als 5 Jahren nach KMT von HLA-identischen Geschwistern, eine Patientin steht noch in ambulanter Behandlung wegen lokalisierter, chronischer Graft-versus-Host Krankheit (GvHK), fünf Patienten sind klinisch gesund. Sechs Patienten starben, ein Patient starb am Tag vor KMT mit Hirnblutung, drei Patienten 32, 40 und 55 Tage nach KMT an den Folgen der Transplantatabstoßung, einer an schwerer GvHK 85 Tage nach KMT und einer 87 Tage nach KMT vermutlich an interstitieller Pneumonie nach Hirnblutung. Drei von 6 Patienten, die nur mit Cyclophosphamid (CY) vorbehandelt waren, starben infolge Abstoßung des Transplantates. Zwei erwachsene Patienten, die mit CY und „total lymphoid irradiation“ vorbehandelt waren, und drei Kinder, die nach KMT unbestrahlte Leukocytenkonzentrate von Knochenmarkspender erhalten hatten, stießen das Transplantat nicht ab. Die Ergebnisse der AG-KMT sind vergleichbar denen großer, spezialisierter Zentren für KMT und zeigen die Möglichkeiten einer Heilung schwerer aplastischer Anämien durch KMT von HLA-identischen Geschwistern. Die Erfolge sind besser bei frühzeitiger KMT.
    Notes: Summary From March 1975 until May 1980 twelve patients with severe aplastic anemia were grafted with bone marrow from HLA-identical siblings by the Munich Cooperative Group for Bone Marrow Transplantation. Six patients are alive between 10 months and more than 5 years after grafting with normal blood values and marrow. One patient is treated as an out patient for chronic localized graft-versus-host disease (GvHD), five patients are well and without treatment. Six patients have died, one patient with a cerebral hemorrhage the day before transplantation, three patients following rejection of grafts 32, 40 and 55 days after grafting, one patient with severe GvHD 85 days after grafting and one patient, probably with interstitial pneumonia, following cerebral hemorrhage. Three of 6 patients who were conditioned with Cyclophosphamide (CY) only died following rejection of the graft. Two adults who were conditioned with CY and “total lymphoid irradiation” and three children, who were given unirradiated leukocyte concentrates from the marrow donor after grafting, did not reject their grafts. The results of the Munich-Cooperative Group for Bone Marrow Transplantation are comparable to those of large, specialized centers for bone marrow transplantation, they indicate possibilities of cure of severe aplastic anemia by marrow grafts from HLA-identical siblings. They confirm that better results are obtained with earlier transplantation in the course of the disease.
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