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  • 1
    ISSN: 1432-1238
    Keywords: Pentoxifylline ; Septic shock ; Cytokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective To evaluate the influence of pentoxifylline (PTX), a phosphodiesterase inhibitor, on cytokines and inflammatory proteins in patients suffering from septic shock. Design Prospective study comparing a therapy group to a matched control group. Setting Medical intensive care unit at a university hospital. Patients Twenty four patients fulfilling the criteria of septic shock were included in this study. Twelve patients received PTX (therapy group) and 12 patients matched for diagnosis, age and gender served as the control group. Interventions Pentoxifylline at 1 mg/kg per hour over 24 h in the therapy group. Measurements ad results Cytokine levels [tumor necrosis factor-α (TNF)], soluble TNF receptor [TNF-R], and interleukin-6 [IL-6] and inflammatory proteins [C-reactive protein, α-1-antitrypsin (AAT), fibronectin, and haptoglobin], as well as hemodynamic parameters and the APACHE III score were evaluated before initiation of therapy and 24 h later. After 24 h, TNF levels were significantly lower in the therapy group (p=0.013), while IL-6 levels were significantly higher in the therapy group (p=0.030). Within the 24 h TNF declined significantly in the therapy group (p=0.006), while IL-6 showed a significant increase (p=0.043). AAT and the APACHE III score tended to differ significantly after 24 h between the groups [AAT levels higher in the therapy group (p=0.05), APACHE III score lower (p=0.05)]. In the therapy group, the systemic vascular resistance index was significantly higher after 24 h (p=0.0026) whereas the cardiac index declined (p=0.035). Conclusions PTX does influence TNF levels in septic shock patients. Nevertheless, inhibiting a single mediator in severe septic shock cannot stop the inflammatory overreaction.
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  • 2
    ISSN: 1432-1238
    Keywords: Key words Pentoxifylline ; Septic shock ; Cytokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To evaluate the influence of pentoxifylline (PTX), a phosphodiesterase inhibitor, on cytokines and inflammatory proteins in patients suffering from septic shock. Design: Prospective study comparing a therapy group to a matched control group. Setting: Medical intensive care unit at a university hospital. Patients: Twenty four patients fulfilling the criteria of septic shock were included in this study. Twelve patients received PTX (therapy group) and 12 patients matched for diagnosis, age and gender served as the control group. Interventions: Pentoxifylline at 1 mg/kg per hour over 24 h in the therapy group. Measurements ad results: Cytokine levels [tumor necrosis factor-α (TNF)], soluble TNF receptor [TNF-R], and interleukin-6 [IL-6] and inflammatory proteins [C-reactive protein, α-1-antitrypsin (AAT), fibronectin, and haptoglobin], as well as hemodynamic parameters and the APACHE III score were evaluated before initiation of therapy and 24 h later. After 24 h, TNF levels were significantly lower in the therapy group (p=0.013), while IL-6 levels were significantly higher in the therapy group (p=0.030). Within the 24 h TNF declined significantly in the therapy group (p=0.006), while IL-6 showed a significant increase (p=0.043). AAT and the APACHE III score tended to differ significantly after 24 h between the groups [AAT levels higher in the therapy group (p=0.05), APACHE III score lower (p=0.05)]. In the therapy group, the systemic vascular resistance index was significantly higher after 24 h (p=0.0026) whereas the cardiac index declined (p=0.035). Conclusions: PTX does influence TNF levels in septic shock patients. Nevertheless, inhibiting a single mediator in severe septic shock cannot stop the inflammatory overreaction.
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  • 3
    ISSN: 1432-1238
    Keywords: Key words Thrombotic ; thrombocytopenic purpura ; Thrombotic microangiopathy ; Hemolytic uremic syndrome ; Intensive Care Unit ; Critical illness ; Plasma exchange
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: Description of diagnostic procedures, treatment modalities and intensive care management of patients with thrombotic thrombocytopenic purpura (TTP). Design: Descriptive study. Setting: Internal medicine Intensive Care Unit (University Hospital of Vienna). Patients: Six patients (two after allogeneic bone marrow transplantation), treated for 12 episodes of TTP. Interventions: Treatment with plasma exchange (fresh frozen plasma, 50–80 ml/kg per day), prednisone (0.75 mg/kg b.i.d.) and, in some cases, vincristine. Supportive therapy as needed. Measurements and results: Patients were admitted to the ICU because of neurological symptoms with acute onset (42% mild, 58% severe), hemolysis and thrombocytopenia. Additional symptoms were fever (50%), bleeding tendency (50%), acute renal failure (42%) and metabolic derangement (8%). Initial laboratory values showed thrombocytopenia (median 17 G/l), hemolysis (median hemoglobin 10.0 g/dl, lactate dehydrogenase 635 U/l, reticulocyte count 175 G/l) with red cell fragmentation. Coagulation tests were normal. Respiratory assist was needed in six episodes (severe seizures, cardiopulmonary resuscitation). In patients without preexisting hematological abnormality the platelet counts exceeded 100 G/l after 3–8 cycles of plasma exchange. In patients after bone marrow transplantation, the platelet counts never exceeded 40 G/l, but the lactate dehydrogenase levels dropped significantly. The neurological symptoms disappeared in all patients and renal function normalized. One patient died before the initiation of therapy. Three patients relapsed 1–3 times between 2 weeks and 5 months after the last episode. The relapses were associated with symptoms similar to the first episode and responded promptly to plasma therapy. Conclusions: TTP is a rare, but life-threatening disorder. It needs immediate diagnosis and has a good prognosis after adequate treatment with plasma exchange.
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  • 4
    ISSN: 1432-0584
    Keywords: Hepatosplenic abscesses ; AML ; Diagnosis ; Sonography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to determine the frequency of hepatosplenic abscesses in AML patients during chemotherapy and to evaluate the clinical and laboratory characteristics of this complication we performed a prospective study over a 28-month period. Fifty-five consecutive patients with de novo AML or relapse who received intensive chemotherapy underwent regular ultrasound examinations. In 16 patients (29.1%) hepatic and/or splenic abscesses were detected sonographically. Histopathological evidence for abscess formation was obtained in five of these 16 patients. In three patients granulation tissue and in one patient necrotizing granulomas were found. Causative micro-organisms were proven in only three patients:Candida hyphae were demonstrated in one patient, gram-positive cocci in another. Bacteria and fungi were seen in the tissue specimen of the third patient. Patients with hepatosplenic abscesses had significantly prolonged fever after neutrophil recovery but did not differ from patients without abscesses in any other laboratory or clinical features. Due to the absence of specific alerting clinical and laboratory signs and symptoms of hepatosplenic abscesses, routine ultrasound examination is required for detection of this complication. The presence of hepatic and/or splenic abscesses does not necessarily worsen the prognosis, but it may influence the decision on further chemotherapy and antimicrobial treatment.
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  • 5
    ISSN: 1432-0584
    Keywords: Acute lymphoblastic leukemia ; Treatment ; Granulocyte colony stimulating factor ; Febrile neutropenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Our purpose was to evaluate the ability of re-combinant human granulocyte colony-stimulating factor (r-metHuG-CSF) as an adjunct to induction chemo-therapy of acute lymphoblastic leukemia (ALL) to ameliorate chemotherapy-induced neutropenia and thus allow patients to receive full doses of chemotherapy on time. Sixteen consecutive patients with adult ALL (13 de novo, three relapsed) were treated with induction chemo-therapy according to the BMFT protocol and received in addition r-metHuG-CSF (200μg/m2/day). Patients who were treated with the same induction chemotherapy but without G-CSF between 1982 and 1990 served as controls. Fifteen of the 16 patients achieved complete hematological remission. One patient died because of fungal septicemia. Compared with historical controls, G-CSF-treated patients had a significantly faster neutrophil recovery in phase I, resulting in neutrophil counts 〉 1000/μl at day 17 vs day 26 (in median) in controls. In phase II, the onset of severe leukocytopenia (〈 1500/μl) was significantly (p = 0.01) delayed and the degree of leukocytopenia less pronounced (mean nadir 3300/μl) in G-CSF-treated patients compared with controls (1880/μl). The number of days of febrile neutropenia was not different in phase I. In phase II it was lower in study patients (0 vs 1.1 days), but the difference did not reach statistical significance (p = 0.09). Full doses of chemo-therapy could be given on time to 11/13 (85%) G-CSF pa-tients but to only 7/30 (23%) controls. These data indicate that (a) G-CSF can be given along with chemotherapy in induction treatment of ALL without compromising efficacy; (b) the duration of neutropenia in phase I is markedly shortened and the degree of leukocytopenia in phase II ameliorated; (c) these beneficial effects allow patients to receive full doses of chemotherapy on time.
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  • 6
    ISSN: 1432-0584
    Keywords: Acute lymphoblastic leukemia Treatment ; Prognostic factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sixty-one consecutive patients with acute lymphoblastic leukemia (ALL) (B-ALL excluded) were treated with the protocol described by Hoelzer et al. [15]. The complete remission (CR) rate was 85% (52/61 patients). Three patients died during induction therapy; six patients were refractory to treatment. The median duration of continuous complete remission (CCR), disease-free survival (DFS), and overall survival was 41.5, 41.4, and 40.8 months, respectively. At 5 years the probability of CCR was 49%, of DFS 43.5%, and of overall survival 41.6%. In the univariate analysis older age (〉35 years,p=0.01), bcr-abl positivity (p=0.007), and time to CR (〉4 weeks,p=0.05) were significantly unfavorable prognostic factors. In the multivariate analysis only age (p=0.006) and time to CR (p = 0.02) remained significant. Thus, our data confirm the high efficacy of this treatment regimen with regard to CR rate and remission duration.
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  • 7
    ISSN: 1432-0584
    Keywords: Key words Acute myeloid leukemia ; Salvage chemotherapy ; Long-term remission
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A total of 168 patients with de novo AML were retreated with chemotherapy at relapse following first CR; 66 patients (39%) achieved a second complete remission (CR). The probability of achieving a second CR was highly dependent on the duration of the first remission. Patients who received no or conventional postremission chemotherapy after second CR had a median remission duration of 7.5 months, and the probability of remaining in remission at 3 years was 24%. Patients with a first CR of more than 12 months had a median second remission duration of 18 months. The probability of a second CCR was 35% at 3 years and 24% at 5 years, whereas none of the patients with a first CR of less than 12 months was in remission at 3 years. Only a poor correlation (p=0.31) was found when the durations of the first and second CR were compared in patients with a second relapse. Patients with long-lasting remissions and long-term survivors after second CR are characterized by a first CR duration of 〉12 months and favorable or normal cytogenetics. The type of salvage treatment seems to be less important for achievment of long-term remission, but it is probably important to administer consolidation chemotherapy after second CR. Other so-far ill-defined factors may be responsible for the supression of the leukemic clone in patients with long-lasting remissions following chemotherapy for relapse after second CR.
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  • 8
    ISSN: 1432-0584
    Keywords: CDR3-PCR ; Clone-specific PCR ; TCRγ-PCR ; Adult B-lineage ALL
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have compared the kinetics of minimal residual disease (MRD) by simultaneous polymerase chain reaction (PCR) monitoring with oligonucleotides for the immunoglobulin heavy chain (IgH) complementarity-determining region 3 (CDR3) and the T-cell receptorγ chain gene (TCRγ), as well as clone-specific CDR3 sequences in adult patients (aged 17–51 years) with acute lymphoblastic leukemia (ALL) who entered a complete hematological remission (CR) after chemotherapy with the German multicenter ALL (GMALL) protocol. The sensitivities were one in 102–3 for the CDR3- and TCRγ-PCR and one in 105–6 for a two-step, seminested CDR3/clone-specific PCR. At diagnosis, 7/7 patients were CDR3 positive and four were TCRγ positive in their bone marrow (BM). At the end of induction therapy (after 2 months) 4/6 tested positive for CDR3, 2/6 for TCRγ, and 5/6 for clone-specific rearrangements. At the end of consolidation treatment (after 7 months) only 1/7 remained positive for CDR3, 2/7 for TCRγ, and 5/7 for clone-specific rearrangements. After an observation period of 18–36 months, 4/7 patients were still in CR and all were PCR negative by the clone-specific method during or after maintenance therapy. Two patients died in leukemic relapse; one patient relapsed but is still alive. All three of these patients remained PCR positive throughout the course of their disease. Clonal evolution in the IgH locus was found in one of these patients. We conclude that the molecular response to chemotherapy in adult B-lineage ALL is slow, even in patients without risk factors other than age. As in childhood ALL, most patients with long-term CR convert to PCR negativity approximately 18 months after the start of chemotherapy. The data also suggest the existence of early clone-specific PCR negativity in a small proportion of long-term survivors. The predictive value of this observation will now have to be confirmed in a larger study.
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  • 9
    ISSN: 1432-0584
    Keywords: Key words CDR3-PCR ; Clone-specific PCR ; TCRγ-PCR ; Adult B-lineage ALL
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We have compared the kinetics of minimal residual disease (MRD) by simultaneous polymerase chain reaction (PCR) monitoring with oligonucleotides for the immunoglobulin heavy chain (IgH) complementarity-determining region 3 (CDR3) and the T-cell receptor γ chain gene (TCRγ), as well as clone-specific CDR3 sequences in adult patients (aged 17–51 years) with acute lymphoblastic leukemia (ALL) who entered a complete hematological remission (CR) after chemotherapy with the German multicenter ALL (GMALL) protocol. The sensitivities were one in 102–3 for the CDR3- and TCRγ-PCR and one in 105–6 for a two-step, seminested CDR3/clone-specific PCR. At diagnosis, 7/7 patients were CDR3 positive and four were TCRγ positive in their bone marrow (BM). At the end of induction therapy (after 2 months) 4/6 tested positive for CDR3, 2/6 for TCRγ, and 5/6 for clone-specific rearrangements. At the end of consolidation treatment (after 7 months) only 1/7 remained positive for CDR3, 2/7 for TCRγ, and 5/7 for clone-specific rearrangements. After an observation period of 18–36 months, 4/7 patients were still in CR and all were PCR negative by the clone-specific method during or after maintenance therapy. Two patients died in leukemic relapse; one patient relapsed but is still alive. All three of these patients remained PCR positive throughout the course of their disease. Clonal evolution in the IgH locus was found in one of these patients. We conclude that the molecular response to chemotherapy in adult B-lineage ALL is slow, even in patients without risk factors other than age. As in childhood ALL, most patients with long-term CR convert to PCR negativity approximately 18 months after the start of chemotherapy. The data also suggest the existence of early clone-specific PCR negativity in a small proportion of long-term survivors. The predictive value of this observation will now have to be confirmed in a larger study.
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  • 10
    ISSN: 1432-0584
    Keywords: Key words Acute myelogenous leukemia ; Stem-cell transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Between February 1982 and 1999, 118 consecutive patients (65 male, 53 female) with acute myelogenous leukemia (AML), with a median age of 35 years (range 17–56 years), received stem-cell grafts from a human leukocyte antigen-identical sibling (n=71), one-antigen-mismatched family member (n=2), matched unrelated donor (n=15), one-antigen-mismatched unrelated donor (n=4) or an autologous (n=26) graft. At the time of transplant, 56 patients were in the first complete remission (CR), 27 in the second CR, 6 in untreated relapse, 17 in primary refractory, and 12 in refractory relapse. The French-American-British classification (FAB) subtypes were as follows: M1 (n=25), M2 (n=28), M3 (n=11), M4 (n=32), M5 (n=16), M6 (n=6). For conditioning, most patients underwent total body irradiation-containing regimens. As of 28 February, 1999, probability of leukemia-free survival (LFS) is 58% for patients after related and 45% after unrelated stem-cell transplantation (SCT). The probability of LFS is 70% for patients given allogeneic transplants in the first CR compared with 33% for those beyond the first CR at SCT. In autologous stem-cell graft recipients, the probability of LFS is 37%. Transplant-related mortality was 28% after related, 20% after unrelated, and 4% after autologous SCT. Probability of relapse for patients given related-donor stem-cell grafts in the first CR and beyond the first CR is 30% and 67%, 55% after unrelated and 63% after autologous stem-cell grafting. Thus, myeloablative therapy followed by allogeneic stem-cell infusion has a high curative potential for patients with AML in remission and offers substantial benefits to patients in advanced disease.
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