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Biomedical subjects

F Hartmann

Publications and source records attributed to F Hartmann.

At least 19 recordsLinked to original sources
PubMed2003

Plasma catecholamines and N-terminal proBNP in patients with acute myocardial infarction undergoing primary angioplasty. Relation to left ventricular function and clinical outcome.

BACKGROUND: Neither profiles nor prognostic values of neurohormonal markers have been prospectively evaluated in patients with acute myocardial infarction (AMI) undergoing primary angioplasty. METHODS AND RESULTS: In 118 consecutive patients with AMI undergoing successful reperfusion (TIMI 2 and 3) by primary angioplasty, plasma concentrations of norepinephrine, epinephrine and N-terminal proBNP (NT-proBNP) were measured before, 60 min and 10 days after angioplasty. Catecholamine concentrations (mean+/-SEM) rose to a maximum in the first hour after angioplasty (norepinephrine: 602+/-44 ng/L, epinephrine: 213+/-24 ng/L) and returned to normal at day 10. Conversely, NT-proBNP levels maintained a further increase from 799+/-44 pmol/L at baseline to 924+/-54 pmol/L at day 10. A NT-proBNP concentration above median at 60 min post-angioplasty predicted major adverse cardiac events (n=27) during the 18-36 month follow-up with an odds ratio of 5.9 (1.7-20.3) and was superior to catecholamines, to left ventricular ejection fraction and to other established postinfarction risk markers. CONCLUSIONS: In a low-risk cohort of patients with AMI undergoing successful reperfusion therapy, plasma NT-proBNP concentrations are elevated for at least ten days. The prognostic value of early plasma NT-proBNP should be further evaluated concerning its ability to facilitate risk stratification of infarct patients.

Aged↗
PubMed2003

Risk-adapted postremission therapy in acute myeloid leukemia: results of the German multicenter AML HD93 treatment trial.

The objective of the AML HD93 treatment trial was to evaluate the outcome in young adults with acute myeloid leukemia (AML) after postremission therapy was stratified according to cytogenetically defined risk. The rationales for the study design were based (i) on previous favorable results with high-dose cytarabine in AML with t(8;21), inv/t(16q22) and in AML with normal karyotype, and ii) on encouraging results obtained in several phase II trials using autologous stem cell transplantation (SCT). Between July 1993 and January 1998, 223 eligible patients, 16-60 years of age with newly diagnosed AML other than French-American-British type M3/M3v, were entered into the trial. Risk groups were defined as follows: low risk: t(8;21) or inv/t(16q22); intermediate risk: normal karyotype; high risk: all other chromosomal abnormalities. Following intensive double induction therapy with idarubicin, cytarabine and etoposide, all patients in complete remission (CR) received a first consolidation therapy with high-dose cytarabine and mitoxantrone (HAM). A second consolidation therapy was stratified according to the risk group: low risk: HAM; intermediate risk: related allogeneic SCT or sequential HAM; high risk: related allogeneic or autologous SCT. Double induction therapy resulted in a high CR rate of 74.5%, and 90% of the responding patients were eligible for consolidation therapy. Survival for all 223 trial entrants was 40%, and for the 166 patients who entered CR, disease-free (DFS) and overall survival were 40 and 51% after 5 years, respectively. Within the low-, intermediate- and high-risk groups, DFS and survival after 5 years were 62.5 and 87, 40 and 49 and 17 and 26% respectively, without advantage for allogeneic transplantation in the intermediate- and high-risk groups. Postremission therapy-related mortality was 0, 7 and 14%, respectively. This study demonstrates the feasibility of cytogenetically defined risk-adapted consolidation therapy. The overall trial results are at least equivalent to those of published trials supporting the risk-adapted treatment strategy.

Acute Disease↗
PubMed2003

Stromal antigen targeting by a humanised monoclonal antibody: an early phase II trial of sibrotuzumab in patients with metastatic colorectal cancer.

BACKGROUND: A novel immunological approach to colon cancer therapy is the antibody targeting of the fibroblast activation protein (FAP), which is highly expressed by stroma cells of this tumour. Unconjugated sibrotuzumab (BIBH 1), which is a humanised version of the murine anti-FAP mAb F19, was investigated for its anti-tumour activity, safety and pharmacokinetics. PATIENTS AND METHODS: Patients with metastatic colorectal cancer received weekly intravenous infusions of unconjugated sibrotuzumab at a dose of 100 mg over 12 scheduled weeks. The study was implemented as an open-label, uncontrolled, multicentre trial. RESULTS: 25 patients were enrolled. Patients had one or more measurable lesions, predominantly liver lesions, at baseline. At least 8 repeated weekly infusions of sibrotuzumab in 17 evaluable patients did not result in complete or partial remission. Rather, ongoing tumour progression was noted in all patients except for 2 patients with stable disease. However, progressive disease was also observed post-study in these 2 patients who received 1 and 6 additional infusions, respectively, of sibrotuzumab. Sibrotuzumab exhibited 2-compartment pharmacokinetics with a dominant terminal phase and t1/2 beta = 5.3 +/- 2.3 days. Adverse drug reactions (rigors/chills, nausea, flushing and one incidence of bronchospasm) were observed in 5 patients. Of the 24 patients given 2 or more infusions of sibrotuzumab, antibodies against sibrotuzumab were found in 3 patients (12.5%) after 4-12 infusions. CONCLUSIONS: Sibrotuzumab was well tolerated and safe. The minimal requirement for the continuation of this exploratory trial, of at least one complete or partial remission, or equivalently, of 4 patients with stable disease, was not met.

Aged↗
PubMed2002

[Increased response rate with rituximab in relapsed and refractory follicular and mantle cell lymphomas -- results of a prospective randomized study of the German Low-Grade Lymphoma Study Group].

BACKGROUND AND OBJECTIVE: Rituximab has shown a high activity in relapsed follicular lymphomas when given alone. Further on, phase-II-studies indicate that its addition to chemotherapy may improve the response rate substantially. However, so far, prospective randomized studies have not been available. PATIENTS AND METHODS: In 1998 the GLSG started a multicenter trial in patients with relapsed or refractory indolent lymphoma or mantle cell lymphoma. A fludarabine-containing regimen (FCM) was chosen for salvage therapy, with fludarabine 25 mg/m(2)/d 1-3, cyclophosphamide 200 mg/m(2) d 1-3 and mitoxantrone 8 mg/m(2) d 1. A total of four courses, every 4 weeks were given. Patients were prospectively randomized for FCM alone or the immunochemotherapy with R-FCM (375 mg/m(2) one day before FCM) RESULTS: About 147 randomized patients 93 had follicular, 40 mantle cell and 14 lymphoplasmocytic/-cytoid lymphoma. Statistical analysis was performed by sequential testing and indicated for 94 fully evaluable patients a significant advantage for the R-FCM-arm, with an overall response rate of 83 % as compared to 58%, when treated with FCM alone (CR: 35 % vs. 13 %). Similar improvements of remission rate were detected in the different lymphoma subgroups, especially in MCL (OR: 65 % vs. 33 %). Both treatment options were associated with hematological toxicities of grade III and IV, but well tolerated; infectious complications were rare, with no difference between the two treatment groups. CONCLUSION: This prospectively randomized trial demonstrates for the first time a significant improvement of the combined immunochemotherapy related to the remission rate in patients with relapsed or refractory indolent lymphoma.

Adult↗
PubMed2002

Prospective randomized trial to evaluate two delayed granulocyte colony stimulating factor administration schedules after high-dose cytarabine therapy in adult patients with acute lymphoblastic leukemia.

In acute lymphoblastic leukemia (ALL), treatment with granulocyte colony stimulating factor (G-CSF) during remission induction shortens granulocytopenia and may decrease morbidity due to infections. However, the optimal timing of G-CSF administration after chemotherapy is not known. In a prospective randomized multi-center study, adult ALL patients were treated with high-dose ARA-C [HDAC, 3 g/m(2) bid (1 g/m(2) bid for T-ALL) days 1-4] and mitoxantrone (MI 10 mg/m(2) days 3-5). They were randomized to receive recombinant human G-CSF (Lenograstim) 263 micro g/day SC starting either from day 12 (Group 1) or day 17 (Group 2). Fifty-five patients (41 male, 14 female) with a median age of 34 years (range: 18-55 years) were enrolled into the study; 50 patients were evaluable. The median duration of neutropenia <500/ micro l after HDAC/MI was 12 days (range: 7-22 days) in the early G-CSF Group 1 and also 12 days (range: 4-22 days) in the late G-CSF Group 2; this was shorter than in the historical control group (15 days, range: 4-43 days, n=46) where the patients received identical cytotoxic treatment without G-CSF. Seventeen infections were observed in 14 patients in Group 1 (47%) and 13 infections in 10 patients in Group 2 (50%) compared to 27 infections in 49 patients of the historical control (54%). In Group 1, the patients received a median of 11 injections with G-CSF (range: 7-22) compared to 7 injections (range: 4-19) in Group 2. The total administered dose of G-CSF in Group 2 was significantly reduced by 40% ( P<0.0001). The delayed start of G-CSF after HDAC/MI in ALL achieves the same clinical benefit compared to the earlier initiation of G-CSF. The reduction of treatment costs by reducing the total G-CSF dose may be important in future treatment with this hematopoietic growth factor.

Adolescent↗
PubMed2002

Less intense conditioning with fludarabine, cyclophosphamide, idarubicin and etoposide (FCIE) followed by allogeneic unselected peripheral blood stem cell transplantation in elderly patients with leukemia.

The objective of this study was to assess toxicity and feasibility of achieving engraftment of allogeneic blood progenitor cells following nonmyeloablative conditioning according to the FCIE protocol (fludarabine 25 mg/m(2)/day, days -7 to -3; cyclophosphamide 200 mg/m(2)/day, days -7 to -3; idarubicin 12 mg/m(2)/day, days -7 to -5; etoposide 250 mg/m(2)/day, days -4 to -3) in elderly patients with leukemia. Eleven patients were included in the study: six patients with acute myeloid leukemia (AML) in complete remission (CR); three patients with refractory or relapsed AML; one patient with chronic myeloid leukemia; one patient with acute lymphoblastic leukemia. The median age of the patients was 62 years. All patients received blood progenitor cells from an HLA-identical sibling with 8.8 x 10(6) CD34(+) cells/kg (median; range 4.7 to 26.2 x 10(6)/kg) and 5.5 x 10(8) CD3(+)cells/kg (median; range 4.5 to 7.9 x 10(8)/kg). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and three courses of methotrexate. The median duration of white blood cell counts <1 x 10(9)/l was 17 days and of platelet counts <50 x 10(9)/l 20 days. In two patients acute GVHD grade I occurred. Nine of 10 patients analyzed developed mixed chimerism. Of seven patients transplanted in CR, three remained in CR 19 to 31 months after transplantation. Three patients with refractory leukemia did not achieve CR, while the patient with relapsed AML achieved a 3rd CR. After a median follow-up time of 22 months, chronic GVHD was mild and limited. The data from this pilot study in elderly patients with leukemia show that the combination of primarily immunosuppressive (FC) and antileukemic (IE) drugs for nonmyeloablative conditioning has moderate nonhematological toxicity and allows engraftment of allogeneic blood progenitor cells.

Adult↗
PubMed2001

Effects of intracoronary low-dose enalaprilat as an adjunct to primary percutaneous transluminal coronary angiography in acute myocardial infarction.

Bradykinin accumulation is a potent cardioprotective mechanism underlying angiotensin-converting enzyme (ACE) inhibition in ischemia and/or reperfusion injury. There is, however, concern about treatment with ACE inhibitors in the very early phase of acute myocardial infarction (AMI) due to adverse systemic hemodynamic effects. We tested the hypothesis that cardiac bradykinin metabolism can be influenced by very low doses of intracoronary ACE inhibitors without harmful systemic effects in patients with AMI. Twenty-two patients with AMI in Killip classes II to III who underwent primary percutaneous transluminal coronary angiography (PTCA) were randomized to intracoronary enalaprilat (50 microg) or saline, given immediately after reopening of the infarct-related artery. Hemodynamics and electrocardiograms were monitored continuously and samples for determination of ACE activity, angiotensin II, bradykinin, kininogen, and cardiac marker proteins were collected from pulmonary arterial and central venous blood. Enalaprilat had no adverse effects on systemic hemodynamics, but rather stabilized arterial pressure and cardiac rhythm during reperfusion. Enalaprilat induced a 70% reduction of ACE activity and a significant increase of bradykinin in pulmonary arterial blood. Angiotensin II was not significantly affected by enalaprilat either in pulmonary arterial or in central venous blood. Myoglobin release was lower and the duration of reperfusion arrhythmias was significantly reduced in the enalaprilat group (p <0.05). Thus, in this pilot study, intracoronary enalaprilat infusion in the infarct-related artery is feasible in the setting of primary angioplasty and is safe and well tolerated. Effective cardiac ACE inhibition can be achieved by low-dose intracoronary enalaprilat, which primarily causes a potentiation of bradykinin.

Angioplasty, Balloon, Coronary↗
PubMed2001

Admission troponin T level predicts clinical outcomes, TIMI flow, and myocardial tissue perfusion after primary percutaneous intervention for acute ST-segment elevation myocardial infarction.

BACKGROUND: In ST-segment elevation myocardial infarction, a troponin T >/=0.1 microg/L on admission indicates poorer prognosis despite early reperfusion. To evaluate the underlying reason, we studied the value of cardiac troponin T (cTnT) for prediction of outcomes, epicardial blood flow, and myocardial reperfusion after primary percutaneous intervention. METHODS AND RESULTS: Patients (n=140) admitted within 12 hours after onset of symptoms were stratified by admission cTnT. Epicardial and myocardial reperfusion were graded by the TIMI score and by measurement of relative increases of myoglobin, cTnT, and creatine kinase (CK)-MB 60 minutes after recanalization, respectively. cTnT was positive in 64 patients (45.7%) and was associated with longer median time intervals to admission (5.5 versus 3.5 hours, P<0.001) and higher mortality rates after 30 days (12.5% versus 3.9%, P=0.06) and 9 months (14% versus 3.9%, P=0.005). cTnT independently predicted a 3.2-fold risk for incomplete epicardial reperfusion (P=0.03). In addition, cTnT >/=0.1 microg/L was associated with more severely impaired myocardial perfusion despite normal epicardial flow, as indicated by lower 60-minute ratios of myoglobin (2.6 versus 7.6, P=0.007), cTnT (6.6 versus 29.2, P<0.001), and CK-MB (3.5 versus 21.4, P=0.002) and a tendency for less resolution of ST-segment elevations (54% versus 60%, P=0.08). CONCLUSIONS: cTnT predicts poorer clinical outcomes, lower rates of postprocedural TIMI 3 flow, and more severely compromised myocardial perfusion despite normal epicardial flow. Thus, a cTnT-positive patient may require more aggressive adjunctive therapy when treated by percutaneous coronary intervention. The impact of preexisting or evolving microvascular dysfunction and the effect of therapies that target myocardial perfusion require further prospective evaluation.

Aged↗
PubMed2001

Salvage treatment with paclitaxel, ifosfamide, and cisplatin plus high-dose carboplatin, etoposide, and thiotepa followed by autologous stem-cell rescue in patients with relapsed or refractory germ cell cancer.

PURPOSE: To study feasibility and efficacy of a new salvage regimen in patients with relapsed and/or refractory germ cell tumors. PATIENTS AND METHODS: Between May 1995 and February 1997, 80 patients were entered onto a phase II study. Conventional-dose salvage treatment with three cycles of paclitaxel 175 mg/m(2), ifosfamide 5 x 1.2 g/m(2), and cisplatin 5 x 20 mg/m(2) (TIP) was followed by one cycle of high-dose chemotherapy (HDCT) with carboplatin 500 mg/m(2) x 3, etoposide 600 mg/m(2) x 4, and thiotepa 150 to 250 mg/m(2) x 3 (CET). In 23 patients, one additional cycle of paclitaxel 175 mg/m(2) and ifosfamide 5 g/m(2) (TI) was given immediately before TIP to improve stem-cell mobilization. RESULTS: Fifty-five (69%) of 80 patients responded to TIP, 24 (30%) of 80 patients had stable disease (n = 5) or tumor progression (n = 19), and one patient died. Only 62 (78%) of 80 patients received subsequent HDCT. Among those, 41 (66%) of 62 patients responded and 20 (32%) of 62 patients had stable disease (n = 3) or tumor progression (n = 17). One patient died after HDCT from multiorgan failure. Survival probabilities at 3 years were 30% for overall and 25% for event-free survival. Peripheral neurotoxicity with sensorimotor impairment grade 2 through 4 in 29%, paresthesias grade 2 through 4 in 24%, and skin toxicity grade 2 through 3 in 15% of patients were the most relevant side effects. CONCLUSION: Treatment with TIP followed by high-dose CET is feasible and can induce long-term remissions in 25% of patients with relapsed or refractory germ cell tumors. Peripheral nervous toxicity in approximately one third of patients is a disadvantage of this salvage strategy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

[Determination of retinal thickness in relation to the age and axial length using optical coherence tomography].

PURPOSE: It is unknown whether the thickness of the retina depends on axial length or on age. We therefore used optical coherence tomography (OCT) to study this relationship. METHODS AND MATERIALS: We recruited 159 subjects aged 13-92 years (205 eyes) without macular pathology. OCT measurements included three horizontal scans and one vertical scan through the fovea. Axial length was determined by an analog high-resolution biometric unit. RESULTS: There was no correlation between retinal thickness and either axial length or age. Mean retinal thickness in the fovea was 142 +/- 18 microns. In the nasal retina thickness was significantly increased to 266 +/- 17 microns, compared to 249 +/- 18 microns in the temporal retina. Retinal thickness in subjects' two eyes was significantly correlated. CONCLUSIONS: Since retinal thickness does not depend upon age or length of the eye, no corrections are necessary when analyzing pathological retinal thickening, such as in diabetic retinal disease.

Adolescent↗
PubMed2001

Course and prognostic implications of QT interval and QT interval variability after primary coronary angioplasty in acute myocardial infarction.

OBJECTIVES: The aim of this study was to determine the influence of early reperfusion on the course of QT interval and QT interval variability in patients undergoing primary percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI) and its prognostic implications on major arrhythmic events during one-year follow-up. BACKGROUND: Although early coronary artery recanalization by primary angioplasty is an established therapy in AMI, a substantial number of patients is still threatened by malignant arrhythmias even after early successful reperfusion, which may be caused by an inhomogeneity of ventricular repolarization despite reperfusion. METHOD: Temporal fluctuations of ventricular repolarization were studied prospectively in 97 consecutive patients with a first AMI by measurements of QT interval and QT interval variability during and after successful PTCA (Thrombolysis in Myocardial Infarction flow grades 2 and 3). Continuous beat-to-beat QT interval measurement was performed from 24-h Holter monitoring, which was initiated at admission before PTCA. RESULTS: Reperfusion caused a significant continuous increase of mean RR interval (738 +/- 98 to 808.5 +/- 121 ms; p < 0.001) and a significant decrease of parameters of QT interval (QTc: 440 +/- 32 to 416.5 +/- 37ms; p < 0.001) and QT interval variability (QTcSD: 27.5 +/- 3 to 24.9 +/- 6 ms; p < 0.001) in the majority of patients. However, in patients with major arrhythmic events at the one-year follow-up (sudden cardiac death, ventricular fibrillation or sustained ventricular tachycardia, n = 15), parameters of QT interval remained unaltered after successful reperfusion (QTc: 447.3 +/- 41 to 432.9 +/- 45 ms, p = NS; QTcSD: 35.1 +/- 13.4 to 29.0 +/- 9.1 ms, p = NS). CONCLUSIONS: Reduction of QT interval and QT interval variability after timely reperfusion of the infarct-related artery may be a previously unreported beneficial mechanism of primary PTCA in AMI, indicating successful reperfusion.

Aged↗
PubMed2001

Cytosine arabinoside, idarubicin and divided dose etoposide for the treatment of acute myeloid leukemia in elderly patients.

Elderly patients with acute myeloid leukemia (AML) have an unfavourable prognoses due to low remission rates, short remission durations, and a high treatment related toxicity. Therefore, new chemotherapy regimens with curative potential, decreased toxicity, and applicability to the majority of these patients are still needed. For remission induction, AML patients > or = 61 years of age received one to three induction courses of the DIVA regimen (idarubicin 10 mg/m2/d days 1 and 3, etoposide 2 x 60 mg/m2/d every 12 hrs. days 2 to 5, and cytarabine 100 mg/m2/d as continuous i.v. infusion days 1 to 5). After achieving CR, patients received two additional courses of DIVA as consolidation therapy. Forty-two consecutive patients with de novo and secondary AML with a median age of 68 years were entered into this trial while six patients were judged ineligible for medical reasons. 62% of the patients achieved a CR, lasting for a median of 26 weeks. Toxicity was mainly hematologic with an early death rate of 12%. The median overall survival for all patients was 38 weeks, and 51 weeks for the 26 patients who achieved CR. Outcome was not significantly different for patients with de novo compared to secondary AML. In conclusion, DIVA showed a promising antileukemic activity and acceptable toxicity as remission induction therapy for de novo and secondary AML in this negligible selected group of elderly patients. However, relapse rate was high, indicating the need for novel approaches for consolidation and maintenance therapy.

Age Factors↗
PubMed2001

An unusual complication of metallic balloon shaft fracture during coronary angioplasty.

We describe two cases of metallic balloon catheter shaft fracture, at a site just proximal to the hemostatic Y-adapter, while attempting to push the stent-balloon assembly through a tortuous left circumflex artery. In both instances, the stent carrying the balloon catheter had a stainless-steel hypotube constituting the proximal stiff portion of the shaft. While no inferences pertaining to this design can be made, our cases call for a closer observation. It would probably be prudent to change the catheter or the dilatation strategy once the shaft started buckling.

Angioplasty, Balloon, Coronary↗