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  • 1
    Electronic Resource
    Electronic Resource
    The procoagulant activity of human granulocytes, lymphocytes and monocytes stimulated by endotoxin (1977)
    Springer
    Journal of molecular medicine 55 (1977), S. 751-757 
    Details
    ISSN: 1432-1440
    Keywords: Endotoxin ; Gewebsthromboplastin in Leukozyten ; Leukozytenisolierung ; Monozyten ; Endotoxin ; Isolation of leukocytes ; Monocytes ; Tissue thromboplastin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Leukocytes from donor blood were separated by Ficoll/Urovison density centrifugation into granulocytes, lymphocytes and monocytes. The cell fractions were suspended in a culture medium to which endotoxin of Salmonella enteritidis was added at a final concentration of 10 µg/ml. Endotoxin-stimulated monocytes developed a very high tissue factor (thromboplastin) activity while in granulocytes an only negligible amount of tissue factor activity was detectable. The tissue factor activity measured in the preparation of the lymphocytes can be explained by contamination with monocytes. Electron microscopic studies showed the lysosomes of all monocytes to be enlarged and activated. Only a fraction of the granulocytes appeared degranulated with prominent vacuoles containing inclusion bodies. Possibly the high tissue factor activity of the monocytes triggers the development of the disseminated intravascular coagulation in the Shwartzman phenomenon.
    Notes: Zusammenfassung Leukozyten aus Spenderblut wurden durch Dichtegradientenzentrifugation über Ficoll/Urovison in Granulozyten, Lymphozyten und Monozyten aufgetrennt. Den in einem Kulturmedium suspendierten Zellen wurde 10 µg/ml Endotoxin von Salmonella enteritidis über mehrere Stunden zugesetzt. Die Stimulierung mit Endotoxin führte bei den Monozyten zu einer sehr hohen Gewebsthromboplastinfreisetzung, während aus Granulozyten so gut wie kein Thromboplastin freigesetzt wurde. Die in Lymphozyten gemessene Aktivität ist auf eine Monozytenverunreinigung zurückzuführen. Elektronenmikroskopisch wiesen alle Endotoxin- stimulierten Monozyten große, aktivierte Lysosomen auf, während nur bei einem Teil der Granulozyten eine Degranulierung und Vakuolisierung mit Einschlußkörpern zur Beobachtung kam. Die hohe Gewebsthromboplastinfreisetzung Endotoxin-stimulierter Monozyten vermittelt möglicherweise die Auslösung der disseminierten intravasalen Gerinnung beim Shwartzman-Sanarelli Syndrom.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01476962
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  • 2
    Electronic Resource
    Electronic Resource
    Lung diseases after bone marrow transplantation (1986)
    Springer
    Journal of molecular medicine 64 (1986), S. 595-614 
    Details
    ISSN: 1432-1440
    Keywords: Lung diseases ; Bone marrow transplantation ; Clinic ; Radiology ; Histology ; Immunology ; Lung function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The case histories of 72 subsequently treated patients — 44 with acute leukemia, 10 with chronic myeloid leukemia, 16 with severe aplastic anemia and 2 with neuroblastoma — were analyzed after bone marrow transplantation (BMT) with respect to pulmonary diseases. Thirty-eight patients suffered from a total of 51 pulmonary complications, which led to death in 20. Of 13 patients, 3 died of bacterial pneumonia, all of them during granulocytopenia; 2 of 6 patients died of fungal pneumonia and 2 out of 3 of a mixed bacterialmycotic infection. Adult respiratory distress syndrome (ARDS) led to death in 2 patients. A granulocyte count under 500/µl correlated significantly (P〈0.002) with the fatal outcome of bacterial, fungal and ARDS pneumonia as well as with bronchitis. Viral pneumonia led to death in 8 of 9 patients; in each there was a significant correlation (P〈0.05) with graft-versus-host disease (GvHD). Patients with repeated episodes of pulmonary illness had significantly more chronic GvHD (P〈0.05); several of these patients displayed a reduction in helper T cells and an increase in suppressor T cells in the peripheral blood. The natural killer (NK) cells were reduced and the percentage of activated NK cell level lay between 6% and 69%. B-cells were absent or deficient. These findings explain in part the absence of specific antibody reactivity. Five of these patients also contracted GvHD-associated obstructive bronchiolitis, which did not respond to therapy. Pulmonary infiltrates of unknown origin (including idiopathic interstitial pneumonia) occurred in 8 of the patients (11.1%), with a fatal outcome in 3 patients. Significant changes (P〈0.05) in lung function after BMT appeared in the form of reduced vital capacity (VC) increased residual volume (RV) and an increase in RV expressed as the percentage of total lung capacity. Pulmonary diseases were the most common complication and cause of death in our patients after BMT.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01735262
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  • 3
    Electronic Resource
    Electronic Resource
    Immunohistological skin alterations in allogeneic bone marrow transplantation (1984)
    Springer
    Journal of molecular medicine 62 (1984), S. 675-688 
    Details
    ISSN: 1432-1440
    Keywords: Immunohistology ; Skin alterations ; Graft-versus-host disease ; Bone marrow transplantation ; Langerhans cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Skin biopsies of 26 patients with leukemia and seven patients with aplastic anemia were investigated before and at different stages after allogeneic bone marrow transplantation (BMT) to establish the immunological criteria which distinguish skin alterations during normal reconstitution from dermal lesions mediated by graft-versushost disease (GvHD). Of the 33 patients studied 27 presented with clinically diagnosed acute and/or chronic GvHD, one patient died of bone marrow rejection. Immunohistological analysis of the respective skin biopsies with selected monoclonal antibodies against human leukocyte antigens (HLA) and differentiation antigens of the lympho-hematopoietic cells revealed low dermal mononuclear cell counts with phenotypically normal constituents in five cases with uncomplicated reconstitution post-grafting. In contrast, increased dermal cellular infiltrates predominantly consisting of Lyt 3+, OKT 8+ T-lymphocytes, as well as of a large number of Ia-like (immune response associated = HLA-D) determinant+ monocytes/macrophages were observed in all patients with active acute/chronic GvH reactivity. As sign of activation simultaneous expression of HLA-D region products was also found on a subset of the invading OKT 8+ T-lymphocytes. Progression of GvHD was associated with additional surface staining of keratinocytes for Ia-like determinants. Loss of Ia-like determinant+, OKT 6+ dentritic epithelial cells in all leukemic patients, as well as in patients with aplastic anemia with or without GvHD suggested damage of Langerhans cells due to the previous radiotherapy and/or specific immunological destruction. In patients with fatal outcome of GvHD prolonged reduction of these dentritic epithelial cells seemed to be indicative of impaired immune reconstitution or bone marrow dysfunction. Thus immunopathological features of skin GvHR may enable early recognition and prognostic evaluation of this disease possibly allowing more effective therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01716464
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  • 4
    Electronic Resource
    Electronic Resource
    CNS manifestations in non-Hodgkin lymphomas (NHL) (1983)
    Springer
    Journal of molecular medicine 61 (1983), S. 903-909 
    Details
    ISSN: 1432-1440
    Keywords: Non-Hodgkin's-Lymphoma ; Central nervous system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a group of 241 patients with non-Hodgkin lymphoma investigated retrospectively, CNS manifestations occurred in 8%, mainly as meningeosis lymphoblastomatosa. Lymphoblastic and immunoblastic NHL showed the highest risk of CNS infiltration (40.7% and 12.5% respectively). Further risk factors were disseminated stage of the disease, prior involvement of the bone marrow and juvenile age. Characteristic symptoms were eye muscle paresis, paresthesias and pareses of peripheral muscles. The most fruitful diagnostic measure was lumbar puncture. More than 80% of the patients observed with CNS manifestations died within one year. The factor limiting life was less the CNS infiltration itself than the systemic progression. CNS prophylaxis should be incorporated in the treatment plan in patients with lymphoblastic and immunoblastic non-Hodgkin lymphoma at an early stage. In contrast CNS prophylaxis is not justified in uncontrollable systemic non-Hodgkin lymphoma spread.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01537530
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  • 5
    Electronic Resource
    Electronic Resource
    Bone marrow transplantation for acute leukemia in second or subsequent remission (1984)
    Springer
    Journal of molecular medicine 62 (1984), S. 1081-1085 
    Details
    ISSN: 1432-1440
    Keywords: Bone marrow transplantation ; Acute leukemia ; Recurrent leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twenty-one patients with acute leukemia in second to fifth remission were treated with bone marrow transplantation: 19 patients with transplants from HLA-matched siblings and two with transplants from identical twins. Twelve patients survived from 15 to 1,625 days after transplantation: six of 11 in the ALL group and six of 10 in the AML group. Recurrence of leukemia after marrow transplantation occurred in five patients. The cause of death in five patients was infection, in two patients combined with graft-versushost disease. Long-term disease-free survival can probably be achieved in 30%–35% of all patients with acute leukemia who receive a marrow transplant in second or subsequent remission.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01711377
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  • 6
    Electronic Resource
    Electronic Resource
    Knochenmarktransplantation bei akuter Leukämie, chronisch myeloischer Leukämie, schwerer aplastischer Anämie und Neuroblastom Stadium IV. Einfluß antiviraler Prophylaxe mit Anti-CMV-Hyperimmunglobulin und Azyklovir (1986)
    Springer
    Journal of molecular medicine 64 (1986), S. 452-466 
    Details
    ISSN: 1432-1440
    Keywords: Bone marrow transplantation ; Anti-CMV hypergammaglobulin ; Azyklovir ; Conditioning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Bone marrow transplantation was performed between IV/82 and X/85 in 64 patients with acute leukemia (n=36), chronic myelogenous leukemia (CML;n=13), severe aplastic anemia (n=12), and neuroblastoma stage IV (n=3). Of these patients 57 received allogeneic marrow from HLA-ABCDR identical, MLC-negative sibling donors. Six transplants were performed with syngenic marrow and one with autologous marrow. Of the 64 patients 48 survived 40-1,250 days after transplantation, resulting in a survival rate (SR) of 75% and a survival probability (SP) of 71%. Of the 36 patients suffering from acute leukemia (SR=64%, SP=51%), patients with acute myelogenous leukemia (AML) in first complete remission (n=11; SR=81%, SP=76%), as well as patients with acute lymphatic leukemia (ALL) in 1st to 4th complete remission at the time of transplantation (n=14; SR=81%, SP=76%) show a favorable prognosis. A poor survival rate was seen for patients with AML when transplanted in second or partial remission (1/5; SR=20%), as well as for patients suffering from ALL and transplanted during relapse or partial remission (1/6; SR=16%). Of 13 patients suffering from CML 12 survived the transplantation free of relapse (SR=93%, SP=92%), and one patient died from varicella zoster pneumonia. Of the transplanted patients with severe aplastic anemia, 12 of 13 are surviving with complete hematologic reconstitution; one patient, however, died on day 10 from a sepsis. In our patient group, the SR as well as the SP has been improved through changes in the irradiation protocol concomitant with prophylactic application of anti-CMV hypergammaglobulin, as well as through additional oral medication of Azyklovir. The 41 patients (BMT No. 7–47) with total body irradiation at one time-show an SR of 44% and an SP of 41%. The following 46 patients (BMT No. 48–93) have reached an SR of 83% and an SP of 74% under the regimen of fractionated total body irradiation, plus prophylaxis with anti-CMV hypergammaglobulin and Azyklovir. Within this group, no fatal CMV pneumonia was encountered as opposed to six patients lost from CMV pneumonia in the first group.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01713171
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  • 7
    Electronic Resource
    Electronic Resource
    Orale Prophylaxe von Herpes-Infektionen mit Acyclovir nach Knochenmarktransplantation: Eine klinische und klinisch-pharmakologische Untersuchung (1986)
    Springer
    Journal of molecular medicine 64 (1986), S. 570-574 
    Details
    ISSN: 1432-1440
    Keywords: Acyclovir, bioavailability ; Drug monitoring ; Bone marrow transplantation ; Herpes infections, prevention and control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Viral infections are one of the major complications after bone marrow transplantation, with high mortality and morbidity. Fourty-six patients between 3 and 48 years old (median 15 years) received orally 400 mg (under age 6, 200 mg) acyclovir 4 times daily from day −12 before to day 84 after BMT. All patients were isolated in laminar-airflow units for at least 23 days with total enteral decontamination. They were concomitantly treated with anti-CMV-hyperimmunoglobulin and cotrimoxazol. During acyclovir prophylaxis seven patients had herpes simplex virus infections, all of them were seropositive before BMT. Acyclovir plasma concentrations were measured by use of a new HPLC method. No acyclovir was present (detection limit 40 ng/ml) in the plasma of five out of six patients with HSV infections. Three of them had non-compliance, and a lack of acyclovir absorption developed in two patients under conditioning regimen. No drug-related side effects were observed. Laboratory tests did not show liver or renal toxicity. Take and hematologic reconstitution were unchanged. In our study, oral acyclovir reduced the incidence of herpes simplex infections after bone marrow transplantation. Herpes infections only occurred in patients with non-compliance or lack of acyclovir absorption.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01735321
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  • 8
    Electronic Resource
    Electronic Resource
    Natural killer cell activity against a thymoma cell line thy 121 in bone marrow transplant recipients (1986)
    Springer
    Journal of molecular medicine 64 (1986), S. 125-130 
    Details
    ISSN: 1432-1440
    Keywords: Bone marrow transplantation ; Natural killer cells ; Interferon ; Cycloporin A ; Graft-versus-host disease ; Methotrexate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twenty-one patients with acute and chronic leukemia or severe aplastic anemia were studied for NK activity against a thymoma cell line (Thy 121) before and after allogeneic bone marrow transplantation. The means of the pretransplant and post-transplant levels did not differ from the mean of 134 NK determinations in 67 healthy donors. There was no correlation between pretransplant NK levels and the appearance of graft-versus-host disease. Three weeks following bone marrow transplantation, pretransplant NK levels were observed. The sensitivity of NK cells to interferon was the same as in normal donors both before and after bone marrow transplantation. In contrast to methotrexate, cyclosporin A inhibited NK activity in patients and controls in vitro. In vivo cyclosporin A treatment, however, did not decrease NK levels in bone marrow recipients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01732635
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  • 9
    Electronic Resource
    Electronic Resource
    Acute folic acid deficiency after bone marrow transplantation (1986)
    Springer
    Journal of molecular medicine 64 (1986), S. 423-432 
    Details
    ISSN: 1432-1440
    Keywords: Bone marrow transplantation ; Folic acid deficiency ; Graft versus host disease ; Megaloblastic marrow ; Hematopoetic recovery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary After bone marrow transplantation (BMT), megaloblastic bone marrow changes are often observed that can only be partially explained by drug effects. Our goal was to find out whether folic acid deficiency represented an additional factor. The serum folic acid concentrations of 41 patients were determined regularly before and after BMT. A 2nd degree polynomial regression analysis revealed a clear and acute drop in folic acid concentrations within 7–9 days after BMT. In 19 patients the level fell below 3.0 ng/ml, the range of folic acid deficiency. The mean folic acid values without oral administration of folic acid after BMT lay significantly below the mean values with substitution (P〈0.001). If a case of acute graft versus host disease (GvHD) was more severe than grade I, the mean folic acid levels were significantly lower (P〈0.01). Patients with megaloblastic bone marrow changes after BMT had significantly lower folic acid values than those without such changes (P〈0.01). The 18 patients with folic acid deficiency had a significantly higher rate of megaloblasts, binucleate erythropoietic precursors, Howell-Jolly bodies, giant myelocytes, and giant metamyelocytes in bone marrow smears than the remaining 23 patients (P〈0.05). Folic acid deficiency did not slow down the increase in leukocytes, granulocytes, thrombocytes, or reticulocytes after BMT. There were 8.2%–9.7% hypersegmented neutrophils in the blood (normal 5%) after BMT both with and without folic acid deficiency. Folic acid deficiency after BMT was caused by insufficient intake combined with simultaneous decreased intestinal resorption and increased requirements for the regeneration of bone marrow and intestinal mucosa.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01727528
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  • 10
    Electronic Resource
    Electronic Resource
    Knochenmarktransplantation bei Patienten mit Leukämien (1982)
    Springer
    Journal of molecular medicine 60 (1982), S. 1279-1287 
    Details
    ISSN: 1432-1440
    Keywords: Bone marrow transplantation ; Acute leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Between October 1979 and March 1982, bone marrow transplantations were performed by the Tübingen Group for BMT on 19 patients with acute leukemia in remission and on one patient with chronic myelocytic leukemia in chronic phase. The conditioning regimen consisted of 2×60 mg cyclophosphamide/kg and 10 Gy whole-body irradiation with the linear accelerator. The lung dose was limited by shielding to 8 Gy. In 15 patients, the bone marrow cell suspension of the donor was preincubated with antihuman T-cell globulin (AHTCG) for prophylaxis of graft-versus-host disease (GVHD). All patients showed prompt engraftment of donor cells with good hemopoietic function and complete chimerism. Under reverse isolation in sterile units, no severe bacterial or fungal infections were seen in the phase of bone marrow aplasia. Twelve in twenty patients survived between 25 and 900 days. A severe GVHD was seen only in two patients — one after preincubation with AHTCG. One patient died from relapse of his leukemia, another patient had a testicular relapse which was treated with local radiotherapy. Major problems were seen with chronic GVHD (six patients) and infectious complications, most importantly interstitial pneumonia, in the late post-transplant period.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01727484
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