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J Kienast

Publications and source records attributed to J Kienast.

At least 37 records · Page 2Linked to original sources
PubMed2000

Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia.

The importance of angiogenesis for the progressive growth and viability of solid tumors is well established. In contrast, only few data are available for hematologic neoplasms. To investigate the role of angiogenesis in acute myeloid leukemia (AML), bone marrow biopsies from 62 adults with newly diagnosed, untreated AML (day 0) were evaluated. Further studies were done after the completion of remission induction chemotherapy (day 16 of induction chemotherapy, n = 21; complete remission, n = 20). Microvessels were scored in at least 3 areas (x500 field, 0.126 mm(2)) of the highest microvessel density in representative sections of each bone marrow specimen using immunohistochemistry for von Willebrand factor and thrombomodulin. Microvessel counts were significantly higher in patients with AML (n = 62) compared with control patients (n = 22): median (interquartile range) 24.0 (21.0-27.8)/x500 field vs 11.2 (10. 0-12.0)/x500 field, respectively (P <.001). On day 16 of induction chemotherapy, microvessel density was reduced by 60% (44-66) (P <. 001) in hypoplastic marrows without residual blasts, in contrast to only 17% (0-37) reduction in hypoplastic marrows with >/= 5% residual blasts (P <.001 for the difference between both groups). Bone marrow biopsies taken at the time of complete remission displayed a microvessel density in the same range as the controls. In conclusion, there is evidence of increased microvessel density in the bone marrow of patients with AML, which supports the hypothesis of an important role of angiogenesis in AML. Furthermore, these findings suggest that antiangiogenic therapy might constitute a novel strategy for the treatment of AML. (Blood. 2000;95:2637-2644)

Acute Disease↗
PubMed2000

Constitutive activation of FLT3 in acute myeloid leukaemia and its consequences for growth of 32D cells.

The receptor tyrosine kinase Flt3 is expressed on leukaemic blasts of most cases with acute myeloid leukaemia (AML). In order to evaluate the presence and significance of constitutive activation of Flt3 for leukaemogenesis, we (1) analysed the expression and activation status of the receptor in AML blasts; and (2) evaluated the functional consequences of constitutively active Flt3 in a myeloid progenitor cell line. Immunoprecipitation studies revealed Flt3 expression in a high proportion of AML cases (27/32) with ligand-dependent Flt3 autophosphorylation in 18, constitutive autophosphorylation in three and no autophosphorylation in six cases. Only one out of three samples with constitutively active Flt3 but 3/18 samples with ligand-dependent autophosphorylated Flt3 contained the recently described internal tandem repeat (ITR) mutations. To test the significance of Flt3 activation in myeloid cell function, we also characterized the biochemical and biological effects of the activating mutation D838V of Flt3 (FLt3D838V) on the factor-dependent myeloid progenitor cell line 32Dcl3: cells transfected with wild-type Flt3 (32D/Flt3) grew FLt3 ligand (FL) dependent, and the receptor was ligand dependently autophosphorylated. In contrast, the receptor was constitutively autophosphorylated in 32D/Flt3D838V cells, which grew independently of FL. We conclude that, in some AML samples, Flt3 is constitutively activated and that this does not correlate with ITR mutations in the juxtamembrane domain. Furthermore, constitutively active Flt3 confers factor independence to the myeloid progenitor cell line 32D. It remains to be determined whether activation of Flt3 is leukaemogenic in vivo and whether strategies aimed at inhibition of Flt3 activation could inhibit leukaemogenesis.

Acute Disease↗
PubMed1999

Overexpression of tissue-type plasminogen activator in atherosclerotic human coronary arteries.

UNLABELLED: The plasminogen activator (PA)/plasmin system is involved in various pathological processes that are considered important features of atherogenesis and atherothrombosis. These include the proteolysis of fibrin deposits and extracellular matrix components as well as the induction of cell migration and mitogenesis. Tissue-type PA (TPA) is a key enzyme mediating plasminogen to plasmin conversion. TPA plasma concentrations are elevated in patients with advanced atherosclerosis and correlate with an increased risk for myocardial infarction and stroke. In this study, we have analysed the content and expression of TPA in human coronary arteries and their relation to the presence and severity of atherosclerotic lesions. METHODS: Segments of coronary arteries obtained from heart explants (n = 15) were classified by the presence and types of atherosclerotic lesions. TPA was quantitatively determined in protein extracts of intimal and medial layers. In situ hybridization and immunohistochemical analyses were performed on serial sections of representative tissue specimens. RESULTS: PA activity entirely attributable to the presence of active TPA was consistently detected in the protein extracts. Extractable TPA antigen and activity showed a significant graded increase in relation to the presence and severity of atherosclerotic lesions. The ratios of active over total TPA were increased several-fold in extracts of advanced lesions despite a concomitant threefold increase in TPA complexed to its inhibitor PA-1. In macroscopically normal arterial segments and in early lesions, TPA was expressed in the endothelium and in colocalization with vascular smooth muscle cells (VSMCs). In advanced plaques, TPA mRNA was mainly detected in the lateral regions of the fibrous caps in association with migrating VSMCs and in the vicinity of the core areas infiltrated by CD68-positive macrophages. CONCLUSIONS: TPA content and expression is consistently increased in relation to the severity of the lesions in atherosclerotic coronary arteries. This may contribute to plaque destabilization and disruption. Conversely, the increased intramural TPA activity may counteract mural fibrin deposition.

Arteries↗
PubMed1999

Improvement of tumor cell depletion by combining immunomagnetic positive selection of CD34-positive hematopoietic stem cells and negative selection (purging) of tumor cells.

One possible reason for relapse after high-dose chemotherapy is retransplantation of tumor cells contaminating autologous hematopoietic stem cell transplants. Residual tumor cells can be diminished by various purging methods. We studied tumor cell depletion by sequentially combining immunomagnetic positive selection of CD34+ hematopoietic stem cells using Isolex50 or Isolex300SA and negative tumor cell depletion using MACS, MaxSep or Isolex50 systems. Using these separation systems in different selection sequences, i.e. positive followed by negative selection (+/- selection) or vice versa, four groups of double selections (Isolex50/MACS, Isolex50/MaxSep, MaxSep/Isolex50, Isolex300SA/Isolex50) were studied. Testing these double-purging procedures mean additional tumor cell depletion (deltaTCD) achieved by the second selection step ranged from 1.1+/-0.58 log (n = 5, +/- Isolex50/MACS) to 2.0+/-1.1 log (n = 7, -/+ MaxSep/Isolex50). Loss of CD34+ cells during double selection sometimes was extensive and mean yield of CD34+ cells ranged from 12.8+/-11.5% (n = 6, +/- Isolex50/MaxSep) to 43.2% (n = 2, +/- Isolex300SA/Isolex50). Calculated values for mean yield-corrected deltaTCD ranged from 0.64+/-0.3 log (n = 5, +/- Isolex50/MACS) to 1.4+/-1.3 log (n = 7, -/+ MaxSep/Isolex50). During positive selection of -/+ selection (MaxSep/Isolex50) relative tumor cell enrichment was detectable leading to an increment of mean tumor cell contamination rate. Best results for total TCD were achieved by the combination of Isolex50/MaxSep (n = 6; TCD: 4.2 log; yield CD34+: 12.8%) and Isolex300/Isolex50 (n = 2; TCD: 3.8 log; yield CD34+: 43.2%). Furthermore, we have established and tested a new simultaneous +/- selection method by using CD34-specific releasing agent PR34+ in the Isolex300i. With this method we have obtained a mean total yield-corrected TCD of 4.7 log (n = 4; range: 4.1-6.0 log) with high CD34+ cell yield (mean: 69.8%) and CD34+ cell purity (mean: 92.8%). Since this new simultaneous +/- purging procedure is safe, applicable within a closed system (GMP-like) and most effective, we recommend it for further testing in a clinical setting.

Antigens, CD34↗
PubMed1999

Tissue plasminogen activator and plasminogen activator inhibitor in patients with acute ischemic stroke: relation to stroke etiology.

Recent studies suggest that high plasma levels of tissue-type plasminogen activator (tPA) and its inhibitor (plasminogen activator inhibitor-1, PAI-1) are markers of an increased risk of atherothrombotic ischemic events such as stroke and myocardial infarction. In this prospective study, we measured tPA antigen, PAI-1 antigen and activity, as well as tPA/PAI-1 complex in patients with acute stroke. Stroke subtypes were classified according to the TOAST criteria. From 132 consecutively screened patients, 89 (100%) were enrolled in this study, including 42 patients (47%) with large artery atherosclerosis (LAA), 32 (36%) with small vessel occlusion (SVO), and 15 (17%) with cardioembolism (CE). Nineteen age-matched neurologic patients without manifestations of cerebrovascular disease served as control subjects (CS). Patients with acute stroke had significantly higher plasma levels of tPA antigen (p < 0.001), PAI-1 antigen (p < 0.05) and PAI activity (p < 0.05) than patients in the control group. t-PA antigen, PAI activity and tPA/PAI-1 complex levels were similar regardless of stroke etiology. Only PAI-1 antigen was lower in patients with cardioembolic stroke than in stroke patients with LAA (p < 0.05). Plasma tPA antigen, PAI-1 antigen, and PAI activity are significantly increased in patients with acute ischemic stroke. Except for PAI-1 antigen, this increase appears not to be related to the underlying stroke etiology.

Acute Disease↗
PubMed1999

Efficacy and safety of simultaneous immunomagnetic CD34+ cell selection and breast cancer cell purging in peripheral blood progenitor cell samples used for hematopoietic rescue after high-dose therapy.

We have established a new simultaneous positive/negative selection procedure using the Baxter Isolex 300i system. We tested its tumor cell (TC) purging efficacy by tumor contamination tests ex vivo and its safety in a group of 17 breast cancer (BC) patients by measuring hematopoietic recovery after high-dose (HD) therapy and autologous stem cell rescue with the selected cells. Tumor contamination tests resulted in a TC depletion of 4.1-6.0 log steps. The CD34+ cell yield in this experimental setting was 38.9-91.5%, and the CD34+ cell purity was 86.0-96.0%. In a group of 17 BC patients (5 high-risk adjuvant, > or = 10 lymph nodes positive, and 12 metastatic), we processed leukapheresis products (LPs) by simultaneous positive/negative selection. In these clinical samples, the mean CD34+ cell yield was 56.2% (range, 14.0-80.1%), and the CD34+ cell purity was 94.5% (range, 69.0-99.8%). Additionally, we screened samples of the patients' LPs before and after the purging procedure for contaminating TC by immunocytochemistry. In 15 of 17 tested cases, TCs were detectable prior to the purging procedure. After the procedure, we could not detect residual TCs in 16 of 17 cases. In one case, we found a highly reduced number of TCs. Furthermore, we evaluated the times for hematopoietic reconstitution in a group of five BC patients in the high-risk adjuvant situation who underwent HD chemotherapy and hematopoietic rescue with positive/negative selected stem cells and compared it with our own data from 10 BC patients who, after identical HD therapy, received only positively selected CD34+ cells and 14 patients who, after identical HD therapy, received autografts purged by incubation with toxic ether lipids (ET-18-OCH3). In all groups, a leukocyte count of >2000 cells/microl was reached at day +10. A platelet count of > 50,000 cells/microl was reached at day +12 in the ET-18-OCH3 group and at day +14 in the other two groups. Furthermore, 12 patients with metastatic disease rescued with positive/negative selected stem cells after HD therapy also showed fast and comparable hematopoietic recovery. The new simultaneous immunomagnetic positive/negative selection using a closed system is effective and safe. Processing LPs leads to a similar CD34+ cell yield, a higher TC depletion compared to standard CD34+ cell selection, and no delay in hematopoietic recovery.

Antigens, CD34↗
PubMed1998

Inflammatory mediators in bronchoalveolar lavage fluid and plasma in leukocytopenic patients with septic shock-induced acute respiratory distress syndrome.

OBJECTIVES: The acute respiratory distress syndrome (ARDS) is a frequent complication of severe sepsis and a major cause of death in patients with hematologic malignancy during chemotherapy-induced leukocytopenia. Inflammatory mediators are important modulators of host response to injury and have been found to be increased in the bronchoalveolar lavage (BAL) fluid of nonleukocytopenic patients with ARDS. Since inflammatory cytokines in plasma of nonleukocytopenic patients seem to be efficient predictors of the course of ARDS, we examined this hypothesis in leukocytopenic patients with septic shock-induced ARDS. DESIGN: Prospective, observational study. SETTING: Intensive care unit (ICU) of a university hospital. PATIENTS: Nineteen patients with leukocytopenia (white blood cell count of <1/nL) following cytoreductive chemotherapy for malignant disorders and severe sepsis with shock-induced ARDS (Murray score of >2.5). INTERVENTIONS: BAL and plasma sampling and ICU management. MEASUREMENTS AND MAIN RESULTS: The proinflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 were measured in the BAL aspirates and in plasma samples, both obtained within 18 hrs after onset of ARDS. Hemodynamic and oxygen metabolism data were measured immediately before plasma samples were taken and BAL was performed. Of the 19 patients studied, nine patients responded to ICU treatment (e.g., mechanical ventilation as indicated by PaO2/FIO2, FIO2, shunt volume, and course of pulmonary infiltrates), whereas ten patients did not respond. BAL cytokine concentrations were significantly increased in nonresponders in comparison with responding patients (TNF-alpha, p = .021; IL-6, p = .008; IL-8, p = .019). In contrast, we did not observe any differences between the groups in terms of plasma cytokine concentrations. CONCLUSION: Determination of cytokine concentrations in BAL samples may be useful for evaluation of severity and course of ARDS in leukocytopenic patients, whereas measurement of plasma cytokines is not helpful.

Adult↗
PubMed1998

Relation of urokinase-type plasminogen activator expression to presence and severity of atherosclerotic lesions in human coronary arteries.

Urokinase-type plasminogen activator (UPA) has been implicated in a broad spectrum of pathological processes - e.g. cell adhesion, migration and proliferation and matrix remodeling - that are considered important features of atherogenesis and plaque disruption. In this study, we have analyzed the content and expression of UPA in human coronary arteries and its relation to the presence and severity of atherosclerotic lesions. Segments of coronary arteries obtained from human heart explants (n = 15) were classified by the presence and types of atherosclerotic lesions. UPA was quantitatively determined in protein extracts of the intimal and medial layers. In situ hybridization and immunohistochemical analyses were performed on serial sections of representative tissue specimens. UPA was detected in the extracts as pro-UPA, UPA complexed to plasminogen activator inhibitor-1, or as otherwise inactive UPA antigen, but not in the active two-chain form. Both functional and total UPA were increased several-fold in extracts of advanced lesions, while the ratios of functional over total UPA showed the opposite trend suggesting enhanced UPA inactivation and turnover. UPA expression in early atherosclerotic lesions was particularly prominent in areas of proliferating SMCs in the abluminal part of the neointima, whereas in advanced lesions UPA was widely expressed in macrophage-rich areas adjacent to the rims and shoulder regions of the necrotic cores. The results strongly suggest a causal involvement of UPA in coronary atherogenesis and its clinical outcome.

Coronary Artery Disease↗
PubMed1997

Inflammatory mediators in BAL fluid as markers of evolving pneumonia in leukocytopenic patients.

STUDY OBJECTIVES: Pneumonia during chemotherapy-induced leukocytopenia is a major cause of overall treatment failure in patients with hematologic malignancies. To improve outcome in these high-risk patients, early diagnosis of pulmonary infiltrates and institution of adequate antimicrobial treatment are mandatory. To identify patients with evolving pneumonia, we have prospectively studied the prognostic value of cytokine and complement measurements in early BAL samples from febrile leukocytopenic patients. DESIGN: Prospective, comparative study. SETTING: Hematology/oncology section of a university hospital. PATIENTS: Twenty-one patients with leukocytopenia (WBC count < 1.000/microL) following cytoreductive chemotherapy for malignant disorders. INTERVENTION: Early BAL sampling primarily for microbiologic diagnostic purposes. MEASUREMENTS AND RESULTS: Proinflammatory cytokines and activated complement components were measured in the BAL aspirates and the results were related to the prevalence or subsequent evolution of overt pneumonia. Of the 21 patients studied, 10 patients presented with overt pneumonia at BAL sampling (group A), 5 patients developed objective signs of pneumonia 3 to 5 days after BAL (group B), and 6 patients remained free of pneumonia during follow-up (group C). In comparison with group C, patients in groups A and B both had distinctly elevated bronchoalveolar levels of tumor necrosis factor-alpha, interleukin-6, granulocyte colony-stimulating factor, C3a, and C5a. CONCLUSIONS: Cytokine and complement determinations in early BAL samples may aid in the identification of febrile leukocytopenic patients with evolving pneumonia 3 to 5 days prior to the manifestation of diagnostic clinical and radiographic signs.

Adult↗
PubMed1997

Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry.

OBJECTIVES: The present study investigated current management strategies as well as the clinical course of acute major pulmonary embolism. BACKGROUND: The clinical outcome of patients with acute pulmonary embolism who present with overt or impending right heart failure has not yet been adequately elucidated. METHODS: The 204 participating centers enrolled a total of 1,001 consecutive patients. The inclusion criteria were based on the clinical findings at presentation and the results of electrocardiographic, echocardiographic, nuclear imaging and cardiac catheterization studies. RESULTS: Echocardiography was the most frequently performed diagnostic procedure (74%). Lung scan or pulmonary angiography were performed in 79% of clinically stable patients but much less frequently in those with circulatory collapse at presentation (32%, p < 0.001). Thrombolytic agents were given to 478 patients (48%), often despite the presence of contraindications (193 [40%] of 478). The frequency of initial thrombolysis was significantly higher in clinically unstable than in normotensive patients (57% vs. 22%, p < 0.001). Overall in-hospital mortality rate ranged from 8.1% in the group of stable patients to 25% in those presenting with cardiogenic shock and to 65% in patients necessitating cardiopulmonary resuscitation. Major bleeding was reported in 92 patients (9.2%), but cerebral bleeding was uncommon (0.5%). Finally, recurrent pulmonary embolism occurred in 172 patients (17%). CONCLUSIONS: Current management strategies of acute major pulmonary embolism are largely dependent on the degree of hemodynamic instability at presentation. In the presence of severe hemodynamic compromise, physicians often rely on the findings of bedside echocardiography and proceed to thrombolytic treatment without seeking further diagnostic certainty in nuclear imaging or angiographic studies.

Acute Disease↗
PubMed1997

Association between thrombolytic treatment and the prognosis of hemodynamically stable patients with major pulmonary embolism: results of a multicenter registry.

BACKGROUND: Thrombolytic treatment has been shown to accelerate resolution of major pulmonary embolism and lead to a rapid improvement of right-side hemodynamics. However, the association between these favorable effects and the clinical outcome of patients who have no severe hemodynamic compromise at presentation remains unknown. METHODS AND RESULTS: The present multicenter registry included 719 consecutive patients with major pulmonary embolism according to clinical, echocardiographic, scintigraphic, and cardiac catheterization criteria. Symptom onset was acute (<48 hours) in 63% of patients. All patients were hemodynamically stable (ie, without evidence of cardiogenic shock) at presentation. Primary thrombolytic treatment (within 24 hours of diagnosis) was given to 169 patients (23.5%), whereas the remaining 550 patients were initially treated with heparin alone. Overall 30-day mortality was significantly lower in the patients who received thrombolytic agents (4.7 versus 11.1%, P=.016). Clinical factors associated with a higher death rate were syncope (P=.012), arterial hypotension (P=.021), history of congestive heart failure (P=.013), and chronic pulmonary disease (P=.032). However, only primary thrombolysis was found by multivariate analysis to be an independent predictor of survival (odds ratio for in-hospital death, 0.46; 95% confidence interval, 0.21 to 1.00). Patients who underwent early thrombolytic treatment had a reduced rate of recurrent pulmonary embolism (7.7 versus 18.7%, P<.001) but also a higher frequency of major bleeding episodes (21.9% versus 7.8%, P<.001). Cerebral bleeding occurred in 2 patients in each treatment group, and 1 patient in each group died of a bleeding complication. CONCLUSIONS: The results of our study suggest that thrombolysis may favorably affect the clinical outcome of hemodynamically stable patients with major pulmonary embolism.

Adolescent↗
PubMed1997

Nitric oxide synthase inhibition by L-NAME in leukocytopenic patients with severe septic shock.

OBJECTIVES: To investigate the effects of nitric oxide synthase inhibition by NG-nitro-L-arginine methyl ester (L-NAME) on hemodynamics and outcome in leukocytopenic (< 1000/microliter) patients with severe septic shock requiring strong vasopressor support. DESIGN: Prospective clinical study. SETTING: Medical intensive care unit. PATIENTS: 10 patients with hematologic malignancies in chemotherapy-induced leukocytopenia with severe septic shock and high-dose vasopressor requirement. INTERVENTION: Continuous intravenous infusion of L-NAME (0.3 mg/ kg per hour) for a study period of 24 h with prolongation for up to 96 h according to individual requirements. MEASUREMENTS AND RESULTS: Compared to baseline values, an increase in mean arterial pressure (p = 0.0021), systemic vascular resistance (p = 0.0001), and left ventricular stroke work index (p = 0.023) with a concomitant decrease in vasopressor requirement (p < 0.05) was observed during the first 24 h of L-NAME treatment. Cardiac output data were unchanged during the study period (p = 0.49). L-NAME was tapered off in five patients who again became responsive to vasopressor medication. Two patients survived the episode of septic shock and vasoactive medication was stopped. CONCLUSIONS: The data demonstrate that inhibition of nitric oxide synthase may be beneficial for the treatment of severe septic shock in leukocytopenic patients as indicated by an increase in systemic vascular resistance, mean arterial pressure, and left ventricular stroke work index.

Adult↗
PubMed1997

Comparative analysis of plasminogen activator inhibitor-1 expression in different types of atherosclerotic lesions in coronary arteries from human heart explants.

OBJECTIVES: Clinical manifestations of coronary heart disease result primarily from the progressive development of atherosclerotic plaques and subsequent thrombus formation: processes which may be accelerated by an enhanced expression of plasminogen activator inhibitor (PAI-1) in the vessel wall. In the present study, content and expression of PAI-1 were comparatively analyzed in human coronary arteries in relation to the presence and severity of atherosclerotic lesions. METHODS: Segments of coronary arteries obtained from heart explants (n = 15) were classified by the presence and types of atherosclerotic lesions. Antigen and activity levels of PAI-1 were determined in protein extracts of intimal and medial layers. In situ hybridization and immunohistochemical analyses were performed on serial sections of representative tissue specimens. RESULTS: Total PAI-1 antigen consistently increased from macroscopically normal areas (MNAs) to early lesions (ELs) and to maximal levels in fibrous (FPs) and calcified (CPs) plaques. No PAI activity was detected, although PAI-1 in its free form was present in all vascular specimens. Both free PAI-1 and PAI-1 complexed with plasminogen activators were significantly increased in extracts of advanced lesions. However, there was a 2-3 fold molar excess of free versus complexed PAI-1 in FPs and CPs. These findings suggest the presence of relevant amounts of PAI-1 in its substrate rather than in its inhibitor conformation in areas of advanced lesions. Compared with MNAs, PAI-1 mRNA was strongly expressed within the thickened intima of ELs. The highest PAI-1 expression was observed in FPs and CPs, being mainly localized in areas surrounding the necrotic cores in co-localization with infiltrating macrophages. CONCLUSIONS: PAI-1 content is consistently increased in relation to the severity of the lesions in atherosclerotic coronary arteries. The concomitant elevation of PAI-1 mRNA suggests that the PAI-1 increase in regulated by local synthesis in the areas of atherosclerotic lesions.

Antigens↗
PubMed1997

Efficacy and kinetics of bone marrow processing and enrichment of haematopoietic progenitor cells (HPC) by a large-volume apheresis procedure.

We investigated the efficacy of bone marrow (BM) processing by an automated large-volume apheresis procedure (6 x original BM volume) in 10 paediatric and adult patients undergoing BM harvesting before myeloablative therapy. Volume-dependent kinetics during apheresis were analyzed by sequential collection of processed cells into a six-fold collection bag system with consecutive analysis of the single bags. BM processing resulted in an 83.3% (+/- 21) recovery of mononuclear cells (MNC), a 97.9% (+/- 1.1) reduction of erythrocytes (RBC) and a 87.7% (+/- 2.9) volume reduction. To determine volume-dependent kinetics of haematopoietic progenitor cell (HPC) enrichment during apheresis, leukocytes (WBC), mononuclear cells (MNC), CD34 cells and colony-forming cells (CFU-GM) were serially quantitated in subsequent collection bags. Large-volume BM processing significantly enhanced absolute yields of CD34+ cells (mean: 4.01 (+/- 2.81) x 10(6)/kg bw) and CFU-GM (mean: 1.92 (+/- 1.47) x 10(4)/kg bw) compared with the standard procedure (3 x BM volume) by 26.9% (+/- 10.9) and 27.2% (+/- 11.6), respectively. We concluded that large-volume apheresis for BM processing is an efficient technique significantly improving the yields of haematopoietic progenitor cells (HPC) without any relevant changes in the purity of the final product. Moreover, sequential collection and analysis of HPC represents a good model to investigate the volume-dependent kinetics and efficacy of BM processing.

Adolescent↗
PubMed1997

Treatment of deep vein thrombosis with low-molecular-weight heparins: a consensus statement of the Gesellschaft für Thrombose-und Hämostaseforschung (GTH).

Recent studies have led to a new concept for the management of deep vein thrombosis. The German Society on Thrombosis and Haemostasis decided to work up the clinical studies in this field published until June 1996 for a consensus statement. The consensus group concluded that (1) high-dose, APTT-controlled subcutaneous administration of unfractionated heparin is as effective as high-dose, APTT-controlled continuous intravenous infusion of unfractionated heparin (grade B recommendation); (2) the anticoagulation with heparin may start at day 1 or 2, overlapping with oral anticoagulants for 7 to 10 days (grade C recommendation); (3) high-dose subcutaneous low-molecular-weight heparins are almost as effective and safe as continuous intravenous infusion of unfractionated heparins (grade B recommendation); (4) no agreement was obtained for the other concomitant treatments of DVT, such as duration of bed rest, use of antiphlogistic drugs, whether LMW heparins are comparable, and whether outpatient treatment can be recommended using LMW heparins.

Anticoagulants↗
PubMed1997

Reciprocal changes in circulating interleukin-6 and its soluble receptor during evolving sepsis in leukocytopenic patients.

Plasma concentrations of interleukin-6 (IL-6) and its soluble receptor (sIL-6R) were serially determined in 32 patients with acute myeloid leukemia who developed severe sepsis (n = 19) or septic shock (n = 13) during chemotherapy-induced leukocytopenia (< or = 1 x 10(9)/L). Starting within 2 h of fever onset, IL-6 levels rose significantly over baseline in both groups to markedly higher levels in patients with evolving septic shock (medians: 372 vs. 3671 pg/mL; P < .001). Simultaneously, sIL-6R significantly decreased to lower levels in shock patients than in septic patients without hypotension (53 vs. 93 ng/mL; P = .02). This pattern was maintained throughout the observation period of up to 6 days. In patients with fatal sepsis, peak IL-6 levels were significantly higher than in survivors (P < .001), whereas minimum sIL-6R levels were markedly lower (P = .003). The reciprocal changes in circulating IL-6 and sIL-6R suggest a role for sIL-6R in modulating the effects of IL-6 during evolving sepsis in leukocytopenic patients.

Acute Disease↗