Search PubMed⌕ Search

Biomedical subjects

M F Fey

Publications and source records attributed to M F Fey.

At least 109 records · Page 6Linked to original sources
PubMed1993

[Emergencies in patients with tumors].

Oncological emergencies are frequent, particularly in advanced cancer stages. Many situations can only be tackled successfully with the cooperation of a well organized team of specialists. Spinal cord compression caused by cancer requires particularly swift action. The diagnosis should include a careful neurological examination. Myelography, once a classical approach in this setting, is increasingly being replaced by nuclear magnetic imaging techniques. Steroids should be given immediately after a diagnosis has been made and further treatment includes surgery, radiotherapy and/or chemotherapy, depending on the type of tumour involved. Febrile patients with severe neutropenia due to myelosuppression by cytostatic drugs often require treatment with intravenous antibiotics. Although hematopoietic growth factors are now available to hasten neutrophil recovery, these drugs should not be given on a routine basis. Another relatively frequent emergency is the superior vena cava syndrome, which is almost always due to a malignant tumour. Any treatment plan prepared to deal with an oncological emergency in a particular patient should take into account the prognosis of the underlying disease, the prospects for further therapy, and the patient's attitude.

Antineoplastic Agents↗
PubMed1993

Factors associated with transfusion requirements during treatment for acute myelogenous leukemia.

Supportive care is a prerequisite for intensive chemotherapy in leukemic patients. Little has been published about quantitative aspects of red blood cell and platelet transfusions. We evaluated transfusion requirements and factors associated with observed differences in 206 patients undergoing initial induction consolidation chemotherapy for newly diagnosed acute myelogenous leukemia. All patients were treated during a 5-year period in 12 hospitals on a common protocol of the Swiss Study Group for Clinical Cancer Research (SAKK). Protocol 30/85 comprises a double induction and one course of consolidation. Of 206 registered patients, 199 were evaluable; 118 of 199 (59%) patients entered completed all three cycles of chemotherapy. These 118 patients received a median (range) of 18 (3-44) units of red blood cells and 12 (2-61) platelet transfusions during 112 (70-129) days of hospitalization. Patients with a hemoglobin > 10 g/l, platelets > 100 x 10(9)/l, and white blood cell counts < 5 x 10(9)/l at diagnosis received fewer transfusions than patients with less favorable blood counts during the first cycle of chemotherapy (p < 0.05). Patients with FAB subtype M3 received more platelet transfusions during the first cycle. Female patients received more platelet transfusions than male patients. In multivariate analyses the participating center was the most important single factor associated with the number of red cell and platelet concentrates given per patient and cycle (p < 0.05), the number of days in hospital (p < 0.05), and the risk of premature withdrawal from the study. These data define factors associated with transfusion requirements in patients treated for newly diagnosed AML. They include severity and subtype of disease at diagnosis, age and sex of the patients, and the participating institution. Results suggest that medical decision-making varies from center to center. The participating institution is strongly associated with differences in transfusion requirements, hospitalization time, and premature withdrawal from study. Leukemia trials tend to focus on the prospective evaluation of chemotherapy or growth factors. Our results suggest that other variables, such as management strategies, should be included for prospective analysis.

Adolescent↗
PubMed1993

Cytostatic drug resistance: parallel assessment of glutathione-based detoxifying enzymes, O6-alkylguanine-DNA-alkyltransferase and P-glycoprotein in adult patients with leukaemia.

The levels of several potential indicators of resistance to cytostatic drugs were measured in leukaemic cells of a total of 64 adult patients with acute or chronic leukaemias before and during treatment and at relapse or recurrence of disease and compared with those of mononuclear cells from the bone marrow of healthy donors. The resistance factors included glutathione (GSH) and its associated enzymes glutathione-S-transferase (GST) and glutathione peroxidase (GPx) as well as O6-alkyguanine-DNA-alkyltransferase (ATase) and P-glycoprotein. Median values for most parameters were significantly higher in leukaemic cells than in those of normal donors although wide interindividual variation in the values of the various parameters, particularly GST, were seen. P-glycoprotein was measurable in 12.5% of untreated leukaemias but in none of the normal donors. The values of the parameters in untreated leukaemic patients were not statistically different from those at relapse or during disease progression. However, the median values for GSH, GST and GPx but not ATase in samples from untreated patients were significantly higher than those in samples taken during drug treatment. Patient response, disease-free survival or duration of remission did not correlate with the values of any of the parameters studied.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Adjuvant chemotherapy after orchiectomy in high-risk patients with clinical stage I non-seminomatous testicular cancer.

In patients with clinical stage I non-seminomatous germ cell tumor the relapse rate seen after orchiectomy alone is approximately 30%. If retroperitoneal lymph node dissection is adopted the relapse rate in patients with histologically negative retroperitoneal nodes is reduced to approximately 10%. Nevertheless, follow-up is still mandatory and 70-80% of clinical stage I patients undergo unnecessary surgery. Metastases and relapses are mostly seen in patients with histological evidence of vascular invasion, growth beyond the testicular capsule and/or embryonal carcinoma in the primary tumor. We conducted a prospective trial of two cycles of cisplatin-based adjuvant chemotherapy for 43 patients with clinical stage I non-seminomatous germ cell tumors and at least one of these risk factors (vascular invasion n = 5, pT > 1 n = 21, embryonal carcinoma n = 42). After a median follow-up of 42 months (12-82 months) 40/41 patients (97.5%) who received the planned chemotherapy remain relapse-free. One patient had surgical excision of a mature teratoma in the ipsilateral iliac region 26 months after orchiectomy and is now disease-free without further treatment after 25+ months. No life-threatening toxicity from chemotherapy was encountered. Two patients who refused the chemotherapy relapsed. In patients with high-risk clinical stage I non-seminomatous testicular cancer two cycles of adjuvant chemotherapy are highly effective in preventing relapses and may be used as an alternative to a 'wait and watch' program or retroperitoneal lymph node dissection, particularly in patients with a compromised follow-up.

Adult↗
PubMed1993

Morphological and functional polymorphism within clonal thyroid nodules.

Thirty-nine thyroid nodules, removed because of recent growth, were analyzed morphologically by serial histological sections for the classical histomorphological hallmarks of follicular cell replication and for immunohistochemically demonstrable overexpression of the growth-associated ras-gene product p21ras. Clonal analysis was performed using the highly informative probe M27 beta that detects polymorphisms on the locus DXS255 of the X-chromosome. Twenty-four nodules were of clonal and 15 nodules were of poly-clonal origin. Only 3 out of the 24 clonal nodules were histomorphologically uniform. In all others, the structural hallmarks of active growth and the P21ras growth-marker expression were remarkably heterogeneous throughout the tumors. There were no histomorphological characteristics distinguishing these clonal tumors from polyclonal nodules. Even if a clonal thyroid tumor may be originally homogeneous in respect to the parameters studied here, mechanisms must exist that create wide heterogeneity of growth and of morphogenetic potential among the individual follicular cells during further expansion of the nodule. Thus, clonal nodules are much more common in nodular goiters than hitherto assumed on grounds of the classical morphological criteria. The diagnosis of a true monoclonal nodule can no longer rely on morphological and functional criteria alone but requires molecular or cytogenetic analysis of clonality.

Adult↗
PubMed1992

[Current molecular prognostic factors in breast carcinoma].

In breast cancer the tumor stage, axillary lymph node metastases and hormone receptors are well established prognostic factors. Nevertheless, additional prognostic factors are still desirable. Recently, attention has focussed on molecular markers, in particular mutated genes involved in the pathogenesis of breast carcinoma. The first such marker to be tested for its clinical relevance has been the c-erbB-2 oncogene. However, the results of the many studies published on this subject are controversial. Further progress can be expected from two different strategies. The molecular pathogenesis of breast cancer must be elucidated in more detail, since it is likely that breast cancer is the result of a progressive accumulation of many different somatic mutations in diverse genes such as oncogenes and tumor-suppressor genes. Rather than relying on retrospective analyses, the clinical relevance of new markers must be tested in prospective clinical trials.

Biomarkers, Tumor↗
PubMed1992

Prevalence of the Rhesus-negative phenotype in Caucasian patients with small-cell lung cancer (SCLC).

We report that the Rhesus (Rh)-negative phenotype is more prevalent in patients with small-cell lung cancer (SCLC) than in the normal Caucasian population (SCLC: 25% Rh-negative vs. 15% expected, p less than 0.0001). This finding has been validated for a Central and a Northern European population (Switzerland and UK). In contrast, the Rh-negative phenotype is no more frequent in non-small-cell lung cancer patients or in heavy smokers with coronary heart disease than in the general population. There was a normal distribution of the ABO blood group phenotype in all patients studied. Whilst the significance of this observation is unclear, we hypothesize that a genetic predisposition to the development of SCLC may be linked to a hitherto unidentified gene on chromosome 1p near the Rh locus. Our observation may perhaps allow further progress to be made in understanding genetic mechanisms of SCLC carcinogenesis.

ABO Blood-Group System↗
PubMed1992

Glucocorticoids downregulate gene expression of GM-CSF, NAP-1/IL-8, and IL-6, but not of M-CSF in human fibroblasts.

Cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage-CSF (M-CSF), neutrophil-activating peptide-1/interleukin-8 (NAP-1/IL-8), and interleukin-6 (IL-6) are pivotal in the regulation of hematopoiesis and immune responses. In mesenchymal cells, their expression is induced by tumor necrosis factor alpha (TNF) and other agents. We now show that, while induction of cytokine expression by TNF in human lung fibroblasts was parallel, glucocorticoid hormones differentially affected their production. Dexamethasone (1 mumol/L) concordantly repressed expression of GM-CSF, NAP-1/IL-8 and IL-6. RNA and protein levels were reduced to approximately 5%, 20%, and 30% of control cells, respectively, as determined by Northern blot analyses and immunoassays. A 50% reduction of RNA levels for all three cytokines occurred in the range of 1 hour. In contrast, dexamethasone (1 mumol/L) did not decrease M-CSF RNA levels and protein release. M-CSF RNA and protein levels were maintained even when dexamethasone (1 mumol/L) was present for the whole duration of a 48-hour TNF stimulation. Further experiments showed that dexamethasone downregulates expression of GM-CSF, NAP-1/IL-8, and IL-6 mainly by decreasing the mRNA stability of these cytokines, and that the dexamethasone-mediated repression of cytokine expression depends on ongoing protein and RNA syntheses. Our study suggests that glucocorticoid hormones repress expression of a set of cytokine genes important in conditions of stress. However, they seem not to affect M-CSF expression, which is likely to be more crucial in maintaining long-term functions of myeloid cells.

Blotting, Northern↗
PubMed1992

Epstein-Barr virus-associated anaplastic large cell lymphoma in renal transplant patients.

A novel association, Epstein-Barr virus-positive Ki-1+/CD30+ anaplastic large cell non-Hodgkin's lymphoma of B-cell phenotype in immunosuppressed renal transplant recipients is reported. Case 1 involved an aggressive clinical evolution, whereas case 2 followed a more "benign" clinical course. Both lymphomas were Epstein-Barr virus-positive as assessed by in situ hybridization, Southern blot, polymerase chain reaction, and immunohistochemical analysis. Both lymphomas contained a single clonal Epstein-Barr virus terminal-repeat fragment. In case 1, clonality was confirmed by the detection of bi-allelic immunoglobulin (Ig) heavy chain gene rearrangement. Case 2 showed germline Ig genes at presentation and oligoclonal Ig heavy chain gene rearrangements at relapse. These results are consistent with the notion that anaplastic large cell lymphoma might arise in a B cell transformed by Epstein-Barr virus at a very early stage, before Ig gene rearrangement. The latter may occur later in the course of clonal evolution, thus permitting investigators to trace intermediate and late stages within a process of multistep lymphomagenesis and/or tumor progression.

Adolescent↗
PubMed1992

Clonal analysis of human tumors with M27 beta, a highly informative polymorphic X chromosomal probe.

The clonality of human tumors can be studied by X inactivation/methylation analysis in female patients heterozygous for X-linked DNA polymorphisms. We present a detailed study on clonal tumor analysis with M27 beta, a highly informative probe detecting a polymorphic X chromosomal locus, DXS255. The polymorphism detected at this locus is due to variable numbers of tandem repeats. The rate of constitutional heterozygosity detected by M27 beta was 88%. Normal tissue from gastrointestinal mucosa and thyroid showed random, hence polyclonal, patterns. Nonrandom clonal X inactivation was detected in all 22 malignant neoplasms that had been shown to be clonal by other DNA markers, such as antigen receptor gene rearrangements or clonal loss of heterozygosity at 17p and other loci. 16/48 normal blood leukocyte samples (33%) showed considerably skewed X inactivation patterns. Comparison of blood leukocytes and normal tissue indicated that in a given individual, X inactivation patterns may be tissue specific. M27 beta was used to study the clonal composition of 13 benign thyroid nodules from 12 multinodular goiters with rapid recent growth, traditionally termed "adenomas." Nine of them were clonal, whereas four nodules and tissue from a case of Graves' goiter were not, indicating that some, but not all, such thyroid nodules may represent true clonal neoplasms. The M27 beta probe permits one to study the clonal composition by the X inactivation approach of a wide variety of solid tumors from most female patients. As a control, normal tissue homologous to the tumor type of interest is preferable to DNA from blood leukocytes, since the latter may show nonrandom X inactivation patterns in a fairly high proportion of cases. M27 beta may, therefore, be of limited use for the clonal analysis of neoplasms derived from hematopoietic cells.

Clone Cells↗
PubMed1991

Dexamethasone and 1,25-dihydroxyvitamin D3, but not cyclosporine A, inhibit production of granulocyte-macrophage colony-stimulating factor in human fibroblasts.

Tumor necrosis factor alpha (TNF alpha) stimulates granulocyte-macrophage colony-stimulating factor (GM-CSF) production in human fibroblasts and other mesenchymal cells. However, relatively little is known about agents that downregulate cytokine production in these cells. In the present report we show that dexamethasone (Dexa), a synthetic glucocorticoid, markedly reduced GM-CSF production in TNF alpha-stimulated fibroblasts at both the protein and the RNA levels. CSF activity, GM-CSF protein, and RNA levels, determined by an in vitro colony-forming assay in normal human bone marrow cells, by an enzyme immunoassay, and by Northern blotting assay, were reduced to greater than 90% of control values by Dexa (1 mumol/L). Similarly, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], a hormone with possible physiologic immunoregulatory significance, reduced GM-CSF expression in a concentration- and time-dependent manner. However, this repression was less pronounced than that of Dexa, and in part due to a decreased proliferative activity. In contrast, cyclosporine A (CsA), another immunosuppressive agent, did not alter GM-CSF expression in TNF alpha-stimulated fibroblasts. Our in vitro studies suggest that by inhibiting GM-CSF production in fibroblasts, glucocorticoids and possibly 1,25(OH)2D3, but not CsA, may attenuate TNF alpha-mediated inflammatory processes and influence the regulation of hematopoiesis.

Calcitriol↗
PubMed1991

[The treatment of acute lymphatic leukemia in adults: pilot project with intensive early therapy without a maintenance phase].

Acute lymphoblastic leukemia (ALL) is conventionally treated in three phases: remission induction, consolidation and maintenance. In adults initial remission rates of nearly 80% can be achieved. The 3 to 5 year leukemia free survival is 20 to 40%. Most relapses occur during maintenance, despite continuous therapy for 2 to 3 years. The value of maintenance therapy following intensive induction in adults is not documented. In this pilot study we treated 34 patients with ALL in five Swiss centers between 1986 and 1989 with intensive induction/consolidation therapy alone. Three induction/consolidation courses were applied: course I, 43 days, consisting of daunomycin, vincristine, prednisone, methotrexate, L-asparaginase and intrathecal CNS prophylaxis; course II, 6 days, consisting of high dose cytosine arabinoside and VP-16; course III, three non randomized arms, either allogeneic or autologous bone marrow transplantation (BMT) or high dose cyclophosphamide and repeated intrathecal therapy alone. 32 patients (94%) reached complete remission (CR): 24 after course I (71%), 7 after course II (cumulative 91%) and one after course III only (cumulative 94%). 3 patients had early, relapses before course III, 3 died of infection, and 2 of graft-versus-host disease. One patient had refractory leukemia in all three courses. 26 patients (76%) were in CR after completion of therapy. 16 relapsed within 1 to 17 months (median 5). 10 patients are free of disease after 10 to 44 months (median 24): 5 had had allogeneic BMT, 3 autologous BMT and 2 cyclophosphamide in course III.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗