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Biomedical subjects

M Freund

Publications and source records attributed to M Freund.

At least 109 records · Page 6Linked to original sources
PubMed1997

[Vertebral body metastases: characteristic MRI findings in epidural infiltration].

PURPOSE: In case of lumbar vertebral metastasis associated with anterior epidural carcinomatous infiltration, we have observed that infiltrations tend to respect the midline. This study led to the systematic recognition of these phenomena in vertebral metastases. MATERIALS AND METHODS: 11 patients with 17 vertebral metastases and adjacent anterior epidural infiltration were reviewed retrospectively. All cases were studied by MRI. The routinely used imaging technique included spin echo (SE) T1 and T2 weighted sequences in the sagittal plane native and T1-SE without and with Gd-DTPA in the axial planes. The radiological findings of these phenomena and the anatomy were studied. RESULTS: We observed these phenomena to be uni- or bilateral in 88.3% of all cases with intraspinal anterior epidural carcinomatous infiltration, especially in that part of the vertebral body where the basal vertebral venous plexus was located. CONCLUSION: We conclude that vertebral metastases respect the midline. We interpret this fact as being due the anatomy of the vertebral body and especially its stabilization by the posterior longitudinal ligament. These findings may be helpful in the differential diagnosis of vertebral body metastases with epidural infiltration in contrast to intraspinal processes which proceed with the destruction of the vertebral body.

Aged↗
PubMed1997

[Dissection of the ascending aorta in pregnancy. Apropos of a case and review of the literature].

Dissection of ascendant aorta is infrequent during pregnancy. Given this low prevalence, diagnosis is often delayed or even unrecognized. This delay in diagnosis can have a highly jeopardizing effect on vital maternal prognosis. In this study, we report a case of ascendant aorta dissection in the 3rd trimester of pregnancy with maternal and fetal survival through combined surgery of a cesarean section and replacement of the ascendant aorta.

Adult↗
PubMed1997

[Vesico-uterine fistula occurring after a normal labor in a patient with a scarred uterus].

We report a vesico-uterine fistula occurring after vaginal delivery in a woman with previous cesarean section. Diagnosis of this rare complication, only 2 cases reported in the literature, is based on clinical findings and retrograde cystography. Medical treatment should be attempted first, but laparotomy is often required for resection of the fistula and simple suture of the bladder and the uterus.

Adult↗
PubMed1997

[Dura thickening adjacent to intracranial, para-dural space-occupying lesions in MRI. Histologic correlation].

PURPOSE: With intracranial tumors a flat, contrast-enhancing, probably dural structure adjacent to the tumor can occasionally be observed on gadolinium-DTPA enhanced MR images. Thers we have attempted to evaluate a tumor infiltration of these enhancement on MRI. MATERIAL AND METHODS: This study included 50 patients, 19 patients had a dural thickening at the tumor base (13 meningiomas and 6 metastases), while 31 patient did not (12 meningiomas and 19 metastases). Studies included plane T2-weighted spin echo (SE) images as well as T1-weighted axial, coronal, or sagittal plains with and without contrast agent. Histopathological examinations, were done on the tumor base adjacent to the dura mater. RESULTS: 7 of 12 meningiomas showed a meningeal thickening on MRI with histopathologically proven tumor infiltration as did also 5 of 6 metastases. But 3 of 12 meningiomas and 15 of 19 metastases without dural thickening at the tumor base also showed tumor invasion into the dura mater. CONCLUSION: MR imaging is still not able to determine whether or not there is a dural infiltration of the tumors base because there was no correlation between MR images and histopathologic results. In conclusion, metastases adjacent to the dura infiltrate the dura mater in a higher percentage than meningiomas.

Aged↗
PubMed1996

[Therapy of chronic myeloid leukemia with interferon-alpha. A decade of experiences].

PATIENTS AND RESULTS: One hundred and fifty-nine patients with chronic myelogenous leukemia have been treated in six studies during 10 years at Hannover Medical School University Center. The prognosis of 111 patients without pretreatment has been improved compared to conventional therapy with a median survival of 5.7 years. Cytogenetic remissions have been induced in all studies followed for a longer time. The most pronounced improvement of prognosis has been observed in these patients. CONCLUSIONS: Several conclusions can be drawn on the basis of the results on the different treatment concepts: 1. Patients with pretreatment have an unfavourable response to interferon. 2. There is a likely effect of the dose of Interferon alpha on the frequency of cytogenetic remissions. 3. The combination of Interferon alpha and interferon gamma has been toxic and ineffective in a pilot study. 4. The combination of interferon and cytosine arabinoside has a positive impact on the frequency of cytogenetic remissions. A continuous parallel application of both drugs seems to be most effective in this respect. An ongoing trial has been initiated to compare a fixed combination of Interferon alpha and cytosine arabinoside and with hydroxyurea respectively. Additionally the feasibility of autologous peripheral blood stem cell transplantation will be studied in patients with insufficient response to the interferon treatment.

Antineoplastic Agents↗
PubMed1996

[Intensive post-remission therapy in acute myeloid leukemia. Results of a prospective comparative study by the South Germany Hemoblastosis Group].

BACKGROUND: To study intensive postremission therapy in adult patients with acute myeloid leukemia myeloablative therapy followed by allogeneic or unpurged autologous bone marrow transplantation (BMT) was compared with high-dose cytosine-arabinoside/daunorubicin (HDAC) consolidation. PATIENTS AND METHODS: 148 de novo AML patients of maximum 50 years (median 36 years, range 16 to 50) were enrolled in the trial. Following induction and early consolidation chemotherapy consisting of daunorubicin, cytosine-arabinoside and VP-16 (DAV), patients with an HLA-identical sibling underwent allogeneic BMT. The other patients received (by randomization or patient's decision) either HDAC or high-dose busulfan plus cyclophosphamide followed by autologous BMT. RESULTS: Hundred and five 105 (70.9%) patients achieved a complete remission. The event-free survival rates after intensive postremission therapy after 72 months were: after BMT (24 patients) 62% (95% confidence interval +/- 19%), after HDAC (44 patients) 36 +/- 16% and after autologous BMT (12 patients) 18 +/- 22%. Thus allogeneic BMT was superior to autologous BMT (p = 0.04), as was HDAC compared to autologous BMT, although not significantly so (p = 0.15). Patients receiving 2 cycles of HDAC had a better 6-year event-free survival rate (47%) and a lower relapse rate (50%) than patients who received only 1 course (29% and 70% respectively). CONCLUSIONS: High-dose busulfan/cyclophosphamide followed by unpurged autologous BMT early after achieving CR had no advantage over high-dose ara-c/daunorubicin. Two cycles of HDAC yielded better results than 1 cycle. The highest event-free survival rate was reached with myeloablative therapy followed by allogeneic BMT.

Adolescent↗
PubMed1996

[10 years transplantation of bone marrow and hematopoietic stem cells in adults at the Hannover Medical School].

PATIENTS AND METHODS: From January 1986 until August 1995 230 adult patients received an allogeneic or autologous transplantation of bone marrow or hematopoietic blood stem cells. The conditioning and myeloablative treatment regimens were chosen according to the underlying disease and type of transplant. RESULTS: The observation period comprises 1 to 115 months after transplantation. After allogeneic transplantation from HLA-identical family donors, the probabilities of disease-free survival were for acute myeloid leukemia in first complete remission (CR) (n = 35) 77%, for acute lymphoid leukemia in 1st CR (n = 7) 72% and in 2nd CR (n = 10) 40%, in first chronic phase of chronic myeloid leukemia (n = 34) 50% and in severe aplastic anemia (n = 7) 100%. Following myeloablative therapy and autologous transplantation the probabilities of disease-free survival were 47% in relapsed Hodgkin's disease (n = 22) and 42% for relapsed high-grade non-Hodgkin's lymphoma (n = 12). Eight of 10 patients with acute myeloid and 7 of 8 with acute lymphoid leukemia suffered a leukemic relapse after autologous bone marrow transplantation. Three of 8 patients with relapsed testicular cancer survived relapse-free. Treatment failures were due to more advanced acute graft versus host disease after allogeneic transplantation and caused by relapse after autologous transplantation. Current protocols evaluate the allogeneic transplantation of enriched CD34+ blood stem cells. In chronic myeloid leukemia the autologous transplantation of blood stem cells after myeloablative therapy is being studied.

Adolescent↗
PubMed1996

Improved outcome in adult B-cell acute lymphoblastic leukemia.

A total of 68 adult patients with B-cell acute lymphoblastic leukemia (B-ALL) were treated in three consecutive adult multicenter ALL studies. The diagnosis of B-ALL was confirmed by L3 morphology and/or by surface immunoglobulin (Slg) expression with > 25% blast cell infiltration in the bone marrow (BM). They were characterized by male predominance (78%) and a median age of 34 years (15 to 65 y) with only 9% adolescents (15 to 20 y), but 28% elderly patients (50 to 65 y). The patients received either a conventional (N = 9) ALL treatment regimen (ALL study 01/81) or protocols adapted from childhood B-ALL with six short, intensive 5-day cycles, alternately A and B. In study B-NHL83 (N = 24) cycle A consisted of fractionated doses of cyclophosphamide 200 mg/m2 for 5 days, intermediate-dose methotrexate (IdM) 500 mg/m2 (24 hours), in addition to cytarabine (AraC), teniposide (VM26) and prednisone. Cycle B was similar except that AraC and VM26 were replaced by doxorubicin. Major changes in study B-NHL86 (N = 35) were replacement of cyclophosphamide by ifosphamide 800 mg/m2 for 5 days, an increase of IdM to high-dose, 1,500 mg/m2 (HdM) and the addition of vincristine. A cytoreductive pretreatment with cyclophosphamide 200 mg/m2, and prednisone 60 mg/m2, each for 5 days was recommended in study B-NHL83 for patients with high white blood cell (WBC) count (> 2,500/m2) or large tumor burden and was obligatory for all patients in study B-NHL86. Central nervous system (CNS) prophylaxis/treatment consisted of intrathecal methotrexate (MTX) therapy, later extended to the triple combination of MTX, AraC, and dexamethasone, and a CNS irradiation (24 Gy) after the second cycle. Compared with the ALL 01/81 study where all the patients died, results obtained with the pediatric protocols B-NHL83 and B-NHL86 were greatly improved. The complete remission (CR) rates increased from 44% to 63% and 74%, the probability of leukemia free survival (LFS) from 0% to 50% and 71% (P = .04), and the overall survival rates from 0% to 49% and 51% (P = .001). Toxicity, mostly hematotoxicity and mucositis, was severe but manageable. In both studies B-NHL83 and B-NHL86, almost all relapses occurred within 1 year. The time to relapse was different for BM, 92 days, and for isolated CNS and combined BM and CNS relapses, 190 days (P = .08). The overall CNS relapses changed from 50% to 57% and 17%, most probably attributable to the high-dose MTX and the triple intrathecal therapy. LFS in studies B-NHL83 and B-NHL86 was significantly influenced by the initial WBC count < or > 50,000/microL, LFS 71% versus 29% (P = .003) and hemoglobin value > or < 8 g/dL, LFS 67% versus 27% (P = .02). Initial CNS involvement had no adverse impact on the outcome. Elderly B-ALL patients (> 50 years) also benefited from this treatment with a CR rate of 56% and a LFS of 56%. It is concluded that this short intensive therapy with six cycles is effective in adult B-ALL. HdM and fractionated higher doses of cyclophosphamide or ifosphamide seem the two major components of treatment.

Adolescent↗
PubMed1996

MRI of encephalitis in children: comparison of CT and MRI in the acute stage with long-term follow-up.

We examined 14 children aged 28 days to 12.7 years with encephalitis by CT or MRI. Of the patients examined by CT 58% had a normal first scan, whereas all MRI investigations demonstrated abnormalities. The clinical features correlated with several MRI investigations. On MRI herpes (HSV) encephalitis started in the medial temporal lobe and encephalomalacia developed within a few weeks. All patients had a follow-up examination 0.5 to 6.5 years after the acute phase. MRI revealed abnormalities in 13 of the 14 children; one boy, with lesions in only the white matter, had a normal follow-up MRI. Even with immediate, optimal therapy the children demonstrated severe parenchymal abnormalities. Signal abnormalities seen in the acute phase of the disease were likely to persist. In children with HSV encephalitis atypical lesions in different areas were seen.

Acute Disease↗
PubMed1996

A D255H substitution in the arylsulphatase A gene of two unrelated Belgian patients with late-infantile metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is an autosomal recessive disease of myelin metabolism caused by a deficiency in the lysosomal enzyme arylsulphatase A (ARSA). We have identified a new mutation in exon 4 of the ARSA gene of two unrelated Belgian patients with late-infantile MLD. The mutation predicts an aspartic acid-to-histidine substitution at position 255 in arylsulphatase A (D255H), in a highly conserved region among sulphatases. Transient expression of the mutation in COS cells did not show an increase in ARSA activity. Both patients were compound heterozygotes carrying the frequent splice site mutation in intron 2 (459 + IG -->A) on the other allele.

Animals↗
PubMed1996

Incidence and implication of additional chromosome aberrations in acute promyelocytic leukaemia with translocation t(15;17)(q22;q21): a report on 50 patients.

Acute promyelocytic leukaemia (APL) is characterized by the translocation t(15;17)(q22;q21). Usually t(15;17) is the sole cytogenetic abnormality, but some patients show other chromosome aberrations in addition to t(15;17). The influence of additional chromosome aberrations on the clinical outcome of patients with t(15;17) is unclear. We have analysed 50 cases of APL carrying the translocation t(15;17). Additional chromosome aberrations were observed in 17/47 patients (36%) studied at initial diagnosis and in all three patients studied at relapse. In nine cases (18%) an additional chromosome 8 and in six cases (12%) an isochromosome of the long arm of the derivative chromosome 17 was observed. Various structural rearrangements in addition to t(15;17) were detected in nine patients (18%). Clinical follow-up data were available for 44 patients studied at diagnosis. A complete remission (CR) was achieved in 34 patients (77%). 10 patients (23%) died within 1 month after diagnosis due to infection or bleeding, eight (24%) relapsed within 10-18 months after initial diagnosis. 28 patients are alive 2-93 months after diagnosis (25 in first CR, two in second and one in third CR) (median follow-up 18.5 months). Bone marrow transplantation was performed in six patients (three in first CR, two in second CR, one in third CR), all are alive and in CR. An influence of secondary chromosome anomalies on prognosis was not observed. However, if a higher rate of long-term remission can be reached, specific secondary chromosome aberrations might turn out to be of prognostic value.

Adolescent↗
PubMed1996

[The CT of calcaneal fractures: 3-D reconstructions with electronic disarticulation].

PURPOSE: To evaluate the clinical value of 3-D-reformations with and without electronic disarticulation of calcaneal fractures compared to axial CT and sagittal reformations. MATERIAL AND METHODS: 25 patients with intra-articular calcaneal fractures underwent diagnostic CT-examinations. Axial slices, sagittal and 3-D-reformations with and without electronic disarticulation were performed. The sagittal and both types of 3-D-reformations were compared to the axial slices with regard to the diagnostic criteria: involvement of articular facets, number of fragments, and traumatic changes of the hindfoot. RESULTS: The best proof of involvement of articular facets is found in axial slices and 3-D-reconstructions after disarticulation followed by sagittal reconstructions. Usually on 3-D-reconstructions without disarticulation articular facets cannot be identified because of overlapping bones. The number of fragments is clearly demonstrated by axial slices and sagittal reconstructions followed by 3-D-reconstructions after disarticulation. Traumatic changes of the hindfoot can be diagnosed in all four forms of visualisation. CONCLUSION: The decisive diagnosis for treatment planning is made based on the axial slices supported by sagittal reformations. In unclarified cases 3-D-reformations after electronic disarticulation may provide further information. 3-D-reformations without disarticulation are useless.

Adult↗
PubMed1996

[The meningeal sign: a new appraisal].

PURPOSE: To evaluate the occurrence of the meningeal sign in meningiomas and metastases. MATERIAL AND METHODS: We studied 20 patients with meningiomas and 17 patients with cerebral metastases adjacent to the dura. MRI studies (Siemens, Magnetom 1,5) included axial T1-weighted and T2-weighted unenhanced as well as gadolinium-DTPA enhanced T1-weighted (axial, coronal, sagittal) SE imaging. In all patients the tumours were resected with the attached dura mater. Histopathological examinations were done, which corresponded to the area of marked enhancement by gadolinium-DTPA. There was no correlation between the occurrence of the meningeal sign and the histopathological examinations. RESULTS: In 20 patients with meningiomas adjacent to the dura we found the meningeal sign in 11 cases. Histologically we observed an increase of collagen fibres and fibrocytes. In 5 of 17 cases with superficial cerebral metastases the meningeal sign was seen, histologically as dura infiltrations and microbleedings. CONCLUSION: The meningeal sign is not specific for meningiomas and can be observed in a wide variety of pathological entities.

Brain Neoplasms↗
PubMed1996

Interferon-alpha enhances the cytotoxic and cytostatic activities of chemotherapeutic drugs in human myeloid leukemia cells.

In comparison with chemotherapeutic drugs, IFN-alpha showed a significantly better median survival rate in CML patients; therefore, current studies focus on the identification of the proper chemotherapeutic drug, with the most effective synergistic interaction with IFN-alpha for the elimination of the human myeloid leukemia cell clone. The cytostatic and cytotoxic effects of combining IFN-alpha with each of the three chemotherapeutic drugs carboplatin, daunorubicin, and cytarabine were evaluated in three human myeloid leukemia cell lines representing different stages of differentiation: MHH225 (CD34-positive multilineage), HL-60 (promyelocytic), and U937 (monoblastic) in both liquid suspension and agar clonogenic cultures. The ED90 (the concentrations of chemotherapeutic drugs required for 90% inhibition of colony formation or cell death) in human myeloid leukemia cells were in the following order: daunorubicin > carboplatin > cytarabine, with HL-60 the most sensitive and MHH225 the least sensitive. Whereas IFN-alpha failed to decrease significantly the ED90 of cytarabine in the three human myeloid leukemia cell lines, it significantly decreased the ED90 of carboplatin and to a lesser extent daunorubicin in both liquid suspension and agar clonogenic cultures. The present results are in line with the previous results of a negative interaction between IFN-alpha and cytarabine both in vitro in K562 human leukemia and in vivo in L1210 murine leukemia, and a synergistic cytostatic interaction between IFN-alpha and carboplatin in K562 cells. The significant synergism between IFN-alpha and carboplatin was observed in all four human myeloid leukemia cell lines with various stages of differentiation and confirmed in both serum-free and serum-supplemented cultures applying different in vitro assays: liquid suspension, agar clonogenic, and capillary agar microclonogenic cultures. Thus, given the in vitro profound synergism between IFN-alpha and carboplatin in all four human myeloid leukemia cells tested, together with the in vivo significant antileukemic activity of both IFN-alpha and carboplatin in several reported clinical studies for myeloid leukemia patients, the clinical use of the combination of IFN-alpha and carboplatin in the treatment of CML patients could prolong the complete hematologic and cytogenetic responses and consequently improve the survival rate. On the other hand, given the negative interaction between IFN-alpha and cytarabine observed in myeloid leukemia cells, together with the inferior cytogenetic responses observed in CML patients treated with the combination of IFN-alpha and cytarabine, caution should be exercised against the continuous clinical use of the combination of IFN-alpha and cytarabine in treating CML patients. In conclusion, the present results suggest the use of carboplatin and to a lesser extent daunorubicin instead of cytarabine in combination with IFN-alpha for the treatment of CML patients.

Antineoplastic Combined Chemotherapy Protocols↗