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Biomedical subjects

M Zimmermann

Publications and source records attributed to M Zimmermann.

At least 73 records · Page 4Linked to original sources
PubMed2001

Short-pulse B-non-Hodgkin lymphoma-type chemotherapy is efficacious treatment for pediatric anaplastic large cell lymphoma: a report of the Berlin-Frankfurt-Münster Group Trial NHL-BFM 90.

Anaplastic large-cell lymphoma (ALCL) accounts for approximately 10% of pediatric non-Hodgkin lymphoma (NHL). Previous experience from NHL-Berlin-Frankfurt-Münster (BFM) trials indicated that the short-pulse B-NHL-type treatment strategy may also be efficacious for ALCL. The purpose of this study was to test the efficacy of this protocol for treatment of childhood ALCL in a large prospective multicenter trial and to define risk factors. From April 1990 to March 1995, 89 patients younger than 18 years of age with newly diagnosed ALCL were enrolled in trial NHL-BFM 90. Immunophenotype was T-cell in 40 patients, B-cell in 5, null in 31, and not determined in 13. Stages were as follows: I, n = 8; II, n = 20; III, n = 55; IV, n = 6. Extranodal manifestations were as follows: mediastinum, n = 28; lung, n = 13; skin, n = 16; soft tissue, n = 13; bone, n = 14; central nervous system, n = 1; bone marrow, n = 5. After a cytoreductive prephase, treatment was stratified into 3 branches: patients in K1 (stage I and II resected) received three 5-day courses (methotrexate [MTX] 0.5 g/m(2), dexamethasone, oxazaphorins, etoposide, cytarabine, doxorubicin, and intrathecal therapy); patients in K2 (stage II nonresected and stage III) received 6 courses; patients in K3 (stage IV or multifocal bone disease) received 6 intensified courses including MTX 5 g/m(2), high-dose cytarabine/etoposide. The Kaplan-Meier estimate for a 5-year event-free survival was 76% +/- 5% (median follow-up, 5.6 years) for all patients and 100%, 73% +/- 6%, and 79% +/- 11% for K1, K2, and K3, respectively. Events were as follows: progression during therapy, n = 2; progression or relapse after therapy, n = 20; second malignancy, n = 1. It was concluded that short-pulse chemotherapy, stratified according to stage, is effective treatment for pediatric ALCL. B symptoms were associated with increased risk of failure. (Blood. 2001;97:3699-3706)

Adolescent↗
PubMed2001

Improved treatment results in high-risk pediatric acute myeloid leukemia patients after intensification with high-dose cytarabine and mitoxantrone: results of Study Acute Myeloid Leukemia-Berlin-Frankfurt-Münster 93.

PURPOSE: To improve outcome in high-risk patients, high-dose cytarabine and mitoxantrone (HAM) was introduced into the treatment of children with acute myelogenous leukemia (AML) in study AML-BFM 93. Patients were randomized to HAM as either the second or third therapy block, for the purpose of evaluation of efficacy and toxicity. PATIENTS AND METHODS: A total of 471 children with de novo AML were entered onto the trial; 161 were at standard risk and 310 were at high risk. After the randomized induction (daunorubicin v idarubicin), further therapy, with the exception of HAM, was identical in the two risk groups and also comparable to that in study Acute Myeloid Leukemia-Berlin-Frankfurt-Münster (AML-BFM) 87. RESULTS: Overall, 387 (82%) of 471 patients achieved complete remission, and 5-year survival, event-free survival (EFS), and disease-free survival rates were 60%, 51%, and 62%, respectively. Idarubicin induction resulted in a significantly better blast cell reduction in the bone marrow on day 15. Estimated survival and probability of EFS were superior in study AML-BFM 93 compared with study AML-BFM 87 (P =.01, log-rank test). This improvement, however, was restricted to the 310 high-risk patients (remission rate and probability of 5-year EFS in study AML-BFM 93 v study AML-BFM 87: 78% v 68%, P =.007; and 44% v 31%, P =.01, log-rank test). Probability of 5-year EFS among standard-risk patients in study AML-BFM 93 was similar to that in study AML-BFM 87 (65% v 63%, P = not significant). Whether HAM was placed as the second or third therapy block was of minor importance. However, patients who received the less intensive daunorubicin treatment during induction benefited from early HAM. CONCLUSION: Improved treatment results in children with high-risk AML in study AML-BFM 93 must be attributed mainly to the introduction of HAM.

Adolescent↗
PubMed2001

Comparative genomic hybridization in childhood acute lymphoblastic leukemia: correlation with interphase cytogenetics and loss of heterozygosity analysis.

We used comparative genomic hybridization (CGH) to study DNA copy number changes in 71 children with acute lymphoblastic leukemia (ALL) including 50 B-lineage and 21 T-ALLs. Forty-two patients (59%) showed genomic imbalances whereby gains were more frequently observed than losses (127 vs. 29). Gains most commonly affected the entire chromosomes 21 and 10 (19.7% each), 6, 14, 18, X (15.5% each), 17 (14.1%) and 4 (11.3%). Highly hyperdiploid karyotypes (chromosome number >50) occurred more frequently in B-lineage than in T-lineage ALL (24% vs. 4.8%). In both cell lineages deletions were mainly detected on 9p (14.1%) and 12p (8.4%), and on 6q in T-lineage ALL (4.2%). These findings were compared with loss of heterozygosity (LOH) of 6q, 9p, 11q, and 12p previously performed in 56 of the 71 patients. Among 54 sites of LOH, CGH revealed losses of the respective chromosome arms in 17 LOH-positive regions (31.5%). G-banding analysis and interphase cytogenetics with subregional probes for 14 loci confirmed the presence of genomic imbalances as detected by CGH. We, therefore, conclude that, in the absence of cytogenetic data, CGH represents a suitable method for identifying hyperdiploid karyotypes as well as prognostically relevant deletions in ALL patients.

Adolescent↗
PubMed2001

Favorable outcome for children and adolescents with T-cell lymphoblastic lymphoma with an intensive ALL-type therapy without local radiotherapy.

In study NHL-BFM 90 we investigated the efficacy of an ALL-type treatment without local radiotherapy for childhood T-cell lymphoblastic lymphoma (T-LBL). In particular, the prognostic impact of the speed of tumor regression was evaluated. From April 1990 to March 1995, 105 evaluable patients, 1.1-16.4 years of age, with T-LBL were enrolled into study NHL-BFM 90. Patients with stage I and II received an 8-drug induction followed by a consolidation including high-dose-methotrexate (MTX) and maintenance therapy up to a total therapy duration of 24 months. Patients with stage III and IV received an additional reinduction and cranial radiotherapy (CRT) (12 Gy for prophylaxis) between consolidation and maintenance. Residual tumor after completion of induction had to be resected. No local RT was applied. Patients received intensified chemotherapy if tumor regression on day 33 of induction was <70% or when vital residual tumor was present after the induction phase. With a median follow-up of 6.41 years, pEFS at 5 years is 91.4% (SE+/-2.7%). 101 patients were evaluable for the speed of tumor response. Two patients received intensified therapy due to <70% tumor regression on day 33. Of 19 patients with tumor residues after induction, 2 relapsed as compared to 4 of 80 patients with complete tumor regression. Our data demonstrate that, with intensive ALL-type chemotherapy but no local radiotherapy, an event-free survival rate of 90% can be achieved in childhood T-LBL. Providing tumor regression within 5 weeks is sufficient, tumor remnants after induction have weak prognostic impact.

Adolescent↗
PubMed2001

[Management of patients with chronic pain syndromes--deficits and perspectives].

Just little more than 10 years ago, pain was still considered a neglected aspect of medicine. Since that time, however, significant progress has been made in this field. The magnitude of the problem is evident from the fact that some 5 million Germans suffer from chronic pain, 600,000 of whom are considered to be particularly affected. It is with regard to these pain patients that the term "chronic pain disorder" has been coined. The mechanisms of progressive pain chronicity form one of the central topics in pain research. The plasticity of neuronal pain systems seems to be particularly relevant in this area. Increasingly, interdisciplinary pain management is available to patients with chronic pain disorder, demonstrating both the possibility of improvement for the chronic pain patient and the reduction in costs for the health care system. The number of such pain treatment/management facilities still needs to be expanded because "divinum est sedare dolorem"--it is divine to alleviate pain (Galen of Pergamon).

Chronic Disease↗
PubMed2001

Open MRI-guided microsurgery of intracranial tumours in or near eloquent brain areas.

OBJECTIVES: Preservation of brain function while maximizing resection is the main aim of brain tumour surgery. The purpose of this study was to evaluate the efficacy of intra-operative magnetic resonance imaging to preserve brain function in patients with tumours in or near eloquent brain areas. METHODS AND MATERIAL: Between August 1997 and January 1999 fifty-eight craniotomies for intracranial tumours or vascular malformations have been performed at the University of Leipzig using a 0.5 T superconducting MR system "SIGNA SP" (General Electric Medical Systems, USA). In 32 of these patients (15 male/17 female) with intracranial tumours, located in or near eloquent brain areas (sensorimotor cortex/speech center), 34 craniotomies were performed using the image guidance of the interventional MRI. RESULTS: Using intra-operative MRI criteria, complete tumour removal could be achieved in 28 (82%) of 34 procedures. In 3 patients only subtotal tumour removal was possible, because the residual tumour was not visible on the intra-operative MR images, but could be identified on early diagnostic follow-up MR-scans. In 3 patients, incomplete tumour resection was performed in order to avoid neurological impairment. In these patients intra-operative MR-images revealed residual tissue abnormalities involving or encroaching on deep brain structures or motor/language cortex. Pre-operative neurological status was unchanged in 24 patients (70%), worsened in 4 patients (12%) and improved in 6 patients (18%). CONCLUSIONS: Intra-operative MRI is helpful for navigation as well as to demonstrate the tumour margins to achieve a complete and safe resection of intracranial lesions located in or near eloquent brain areas. It enables an image based functional monitoring of the brain which is critical for motor, sensory or language function. Complications related to the surgical procedure are reduced and the risk of neurological deterioration due to tumour removal and postoperative complications is minimized.

Adult↗
PubMed2001

The risk of haemorrhage associated with early postoperative heparin administration after intracranial surgery.

BACKGROUND: To analyse the rate of postoperative haemorrhage during a 4-year period of early postoperative administration (< 24 hours) of fractionated heparin plus compression stockings in a large cohort of patients undergoing intracranial surgery. METHOD: A total of 1564 patients who underwent intracranial surgery at our institution were included in our study. 1197 of the 1564 patients (77%) had major intracranial surgery (group 1). Group 2 was made up of 367 patients in whom ventriculoperitoneal shunting or external ventriculostomy was performed (minor intracranial procedures). All patients were investigated retrospectively for the occurrence of major postoperative haemorrhage confirmed by CT scanning and requiring surgical evacuation. The protocol for prophylaxis of thrombo-embolic events included early (< 24 hours) postoperative fractionated low-dose heparin (3 x 5000 IE subcutaneously) until discharge plus intra- and postoperative compression stockings. FINDINGS: Major postoperative haemorrhages were observed in 31 of the 1564 patients (2.0%). In three patients, the haemorrhage occurred on the day of surgery before the administration of heparin. The haemorrhage rate of patients receiving heparin was 1.8% (28/1564). All haemorrhages occurred in patients undergoing major intracranial procedures (group 1; 31/1197; 2.6%). There was no haemorrhage in minor intracranial procedures (group 2; 0/367; 0%). INTERPRETATION: Although retrospective, this is to date the largest study supporting the concept of postoperative pharmacological thrombo-embolic propylaxis in patients undergoing intracranial surgery. The question as to whether pharmacological prophylaxis is beneficial for a given patient can only be answered by weighing the risk reduction of thrombo-embolic events against the risk increase of postoperative haemorrhage associated with different surgical procedures and heparin protocols.

Adolescent↗
PubMed2001

Intervertebral disc calcification in childhood--a case report and review of the literature.

The authors report the case of a 10-year-old girl with intervertebral disc calcifications from the levels C6/C7 to Th1/Th2, presenting with a herniated calcified intervertebral disc at the C7/Th1 level, causing spinal cord compression with subsequent progressive paresis and sensory loss of her left leg. After anterior cervical discectomy and fusion the neurological deficits completely resolved within 2 weeks. It can be concluded that calcification of an intervertebral disc is a rare syndrome in childhood, causing progressive neurological deficit only in a few reported cases. Although the treatment of choice is conservative, surgery is required in patients who develop progressive neurological deficit.

Calcinosis↗
PubMed2001

Neuropeptides: brain messengers of many faces.

Neuropeptides 2001, 2nd Joint Meeting of the European Neuropeptide Club and the American Summer Neuropeptide Conference (11th Annual Meeting). 6-11 May 2001 with Satellite Symposium, Israeli-French Symposium, Israel Ministry of Science, Culture and Sport, 6 May 2001, held at Maale Hachmicha and Tel Aviv University, Israel.

Animals↗
PubMed2001

Idarubicin improves blast cell clearance during induction therapy in children with AML: results of study AML-BFM 93. AML-BFM Study Group.

In the randomized trial AML-BFM 93 we compared 60 mg/m2/day daunorubicin with 12 mg/m2/day idarubicin for 3 days each, combined with cytarabine and etoposide during induction. Results showed a significant better blast cell reduction in the bone marrow on day 15 in patients of the idarubicin arm (25 of 144 = 17% of patients with > or = 5% blasts compared to 46 of 149 = 31% of patients after daunorubicin, Pchi2 = 0.01). This was, however, mainly seen in high risk patients treated with idarubicin (19% vs 38%, Pchi2 = 0.007). Cardiotoxicity, WHO grade 1-3 shortening fraction reduction after induction occurred in 6% patients in both arms. Bone marrow toxicity differed slightly with a median recovery time of neutrophils >500/microl of 25 days (daunorubicin) compared to 27 days (idarubicin), P = 0.05. In the total group of patients probabilities of 5 years event-free survival and disease-free survival were similar for patients treated with daunorubicin or idarubicin (49% +/- 4% vs 55% +/- 4% and 57% +/- 4% vs 64% +/- 4%, P logrank 0.29 and 0.15, respectively). However, in patients presenting with more than 5% blasts on day 15 there was a trend for a better outcome after treatment with idarubicin (P logrank 0.06). Together with the early effect seen for high risk patients these results indicate a better efficacy of idarubicin than of daunorubicin during induction with a similar rate of toxicity.

Antibiotics, Antineoplastic↗
PubMed2001

Liposomal amphotericin B for prophylaxis of invasive fungal infections in high-risk paediatric patients with chemotherapy-related neutropenia: interim analysis of a prospective study.

Invasive fungal infections (IFI) are a major cause of morbidity and mortality in patients with cancer. A retrospective analysis of children with cancer at high risk for IFI treated at Münster University Hospital showed that the incidence (7.4% vs. 1.8%) and lethality (28.1% vs. 0) of documented IFI were lower in patients receiving systemic antifungal prophylaxis with liposomal amphotericin B (l-AmB) in comparison to a historical control group. To determine whether this decline in incidence and lethality was due to antifungal prophylaxis or was produced by advances in diagnostic procedures and early empirical antifungal therapy, a prospective study was initiated. Patients in the prophylaxis arm received thrice-weekly 1 mg kg(-1) body weight l-AmB, whilst patients in the early intervention arm received no prophylaxis. Diagnostic procedures and antifungal therapy for suspected or proven IFI were initiated as clinically indicated for all patients. The primary endpoint of the study was the incidence of IFI. Secondary endpoints were the use of therapeutic doses of l-AmB, the safety of prophylactic l-AmB, and the total consumption of l-AmB for antifungal therapy. The interim analysis after 1 year showed no differences between the two approaches with respect to the incidence of IFI and to safety issues.

Adolescent↗
PubMed2001

A new endotoxin adsorber: first clinical application.

In an open, uncontrolled pilot study, 5 men and 1 woman with suspected gram-negative sepsis were treated with a new whole-blood endotoxin adsorption system. Lipopolysaccharide (LPS) adsorption was carried out by hemoperfusion over high-affinity polymethacrylate-bound albumin (Fresenius Endotoxin Adsorber EN 500). All patients suffered from endotoxemia (>20 pg/ml LAL) and met at least two systemic inflammatory response syndrome (SIRS) criteria. Four patients suffered from pneumonia due to mechanical ventilation, one from peritonitis, and one from pneumonia and peritonitis. Endotoxin adsorption was very well tolerated, and efficient LPS removal was shown in all patients. Apache II score immediately before immunoadsorption was 23.5 and was 22.3 after the last treatment. All 6 critically ill patients improved substantially and were discharged from the intensive care unit. LPS whole blood immunoadsorption is a promising new method. No side effects have been observed thus far. A large controlled study to prove clinical efficacy in patients with severe sepsis is under way.

APACHE↗
PubMed2001

Fluctuation in autonomic tone is a major determinant of sustained atrial arrhythmias in patients with focal ectopy originating from the pulmonary veins.

INTRODUCTION: This study was designed to analyze dynamic changes in autonomic tone preceding the onset of sustained atrial arrhythmias in patients with focal atrial fibrillation (AF) to determine why patients with frequent discharge from the arrhythmogenic foci develop sustained AF. METHODS AND RESULTS: Holter tapes from 13 patients (10 men and 3 women; mean age 53 +/- 5 years) with paroxysmal "lone" AF (mean 18 +/- 13 episodes per week) and a proven focal origin (pulmonary veins in all cases) were analyzed. A total of 38 episodes of sustained (>30 min) were recorded and submitted to frequency-domain heart rate variability analysis. Six periods were studied using repeated measures analysis of variance: the 24-hour period, the hour preceding AF, and the 20 minutes before AF divided into four 5-minute periods. A significant increase in high-frequency (HF, HF-NU) components was observed during the 20 minutes preceding AF (P = 0.003 and 0.002, respectively), together with a progressive decrease in normalized low-frequency (LF-NU) components (P = 0.035). An increase in LF/HF ratio followed by a linear decrease starting 15 minutes before sustained AF also was observed, indicating fluctuations in autonomic tone, with a primary increase in adrenergic drive followed by a marked modulation toward vagal predominance immediately before AF onset. CONCLUSION: In patients with focal ectopy originating from the pulmonary veins, sustained episodes of atrial arrhythmias are mainly dependent on variations of autonomic tone, with a significant shift toward vagal predominance before AF onset.

Adult↗
PubMed2001

Differential time courses of skin blood flow and hyperalgesia in the human sunburn reaction following ultraviolet irradiation of the skin.

The response of skin to ultraviolet (UV) irradiation is an inflammation with pronounced vasodilation and hyperalgesia. Volunteers underwent UV irradiation of patches of forearm skin 3 cm in diameter. The intensity of the UV irradiation (290-320 nm) ranged between 133 mJ/cm2 and 400 mJ/cm2. Changes in skin blood flow were measured with laser Doppler technique at 3, 6, 9, 12, 24, 30, 36, 48, 60, 72, 96 and 216 h post UV irradiation. The alteration in pain threshold was measured for heat with a Peltier thermode and for pressure with a metal stylus. The effect of repeated topical pre-treatment 4 days prior to UV irradiation with 1.5 g of 0.04% capsaicin containing ointment was also investigated.UV irradiation resulted in a dose-dependent increase of skin blood flow for more than 96 h post-irradiation. There were two peaks of blood flow at 12 h and 36 h. Topical application of capsaicin prior to UV irradiation attenuated blood flow from 30 h to 45 h post UV irradiation. Enhanced blood flow was also present 5 mm outside the irradiated area (flare reaction). The control level of heat pain threshold was 44.5+/-0.7;C in normal skin. Heat pain thresholds were lowered by up to 7.761.2;C in UV-irradiated areas in a dose-dependent fashion. The control level of pressure pain threshold was 15.260.3N. Pressure pain thresholds were lowered by up to 6 N in irradiated areas. Maximal hyperalgesia coincided with the second peak of skin blood flow between 30 h and 60 h post UV irradiation. The effects of topical application of capsaicin suggests an involvement of neuropeptide mechanisms in the late phase of the human sunburn reaction.

Adult↗
PubMed2001

Rivet-like titanium clamp fixation of cranial bone flaps during open magnetic resonance-guided neurosurgery.

A new implant technique for bone flap fixation after magnetic resonance image-guided neurosurgical procedures in the first vertical open 0.5T MRI scanner is described. Between May 1998 and December 1998 cranial bone flap refixation was performed in 20 patients using rivet-like titanium cranial bone flap fixation clamps. In all cases, a safe and solid refixation of the bone flap was achieved. Intraoperative and postoperative MRI quality was not influenced. Rivet-like titanium clamp bone fixation is a safe procedure which can be easily performed under the special circumstances during neurosurgical operations with interventional MRI.

Humans↗