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Biomedical subjects

M Martelli

Publications and source records attributed to M Martelli.

At least 73 records · Page 4Linked to original sources

Anaplastic large cell lymphoma (CD30 +/Ki-1+): results of a prospective clinico-pathological study of 69 cases.

Sixty-nine anaplastic large cell lymphomas (ALCLs) were selected from an Italian comparative trial on MACOP-B and F-MACHOP. As no significant difference in effectiveness of the protocols emerged, they were considered homogeneously treated. The ALCLs were divided into two groups according to previously defined criteria: 41 were common type (ALCLs-CT) and 28 Hodgkin-related (ALCLs-HR). T-cell phenotype was most common (58%), while B-cell, null and hybrid forms accounted for 27%, 13% and 2%. Clinically, ALCLs CT and HR differed as to mean age (27 v 34.3 years) and presentation; all ALCLs-HR showed mediastinal involvement, with bulky disease in 57%, and more frequent occurrence in stage II. In contrast, ALCLs-CT showed mediastinal masses in 58.5%, infrequently revealed bulky disease (24%), and were not specifically associated to stage. Among the ALCLs-CT, 68.4% achieved complete remission (CR), 24.4% partial remission (PR), one (2.4%) was resistant to therapy, and two (4.8%) had fatal drug toxicity. Of the ALCLs-HR, 67.8% reached CR, 14.3% PR, and 17.9% did not respond. In CR, ALCLs-CT showed a greater tendency to relapse (32.1% v 14.2%). At present, 65.8% of ALCLs-CT and 67.8% of ALCLs-HR are alive with overall survival/disease-free survival averages of 31/27 and 29/24 months respectively. Our data emphasize that, independently of subtype, ALCLs benefit from the application of third-generation protocols for high-grade non-Hodgkin's lymphomas.

Adolescent↗

[The regulation of endometrial and trophoblastic metalloproteinases during blastocyst implantation].

The trophoblastic cells of the blastocyst and of the placenta express an invasive phenotype. These cells produce and secrete metalloproteinases which are capable of digesting the extracellular matrix and invade it. The different endometrial cells produce the same enzymes and favour thus the implantation process. Among the numerous endometrial factors that control trophoblastic invasion, the components of the extracellular matrix such as laminin and fibronectin, play an important role. These glycoproteins, control the proteolytic activity of the invading cells by binding to their receptors (integrins) expressed on the cell membrane. When these receptors are distributed in a non polarised way they don't bind their ligands and the cells secrete proteases and invade the endometrium. Conversely, when the receptors are clustered, they bind to their ligands and the cell's invasive behaviour and protease secretion is inhibited. The endometrial extracellular matrix is thus a potent regulator of trophoblast invasion.

Embryo Implantation↗

P-VABEC: a prospective study of a new weekly chemotherapy regimen for elderly aggressive non-Hodgkin's lymphoma.

PURPOSE: To evaluate, in a prospective trial, a new combination chemotherapy specifically designed for elderly patients. PATIENTS AND METHODS: From October 1988 to December 1990, 60 previously untreated patients older than 60 years of age with aggressive non-Hodgkin's lymphoma (NHL) were treated at our institution with a new weekly alternating six-drug chemotherapy regimen, P-VABEC. The schedule consisted of doxorubicin, etoposide, and cyclophosphamide alternated weekly with vincristine and bleomycin. Oral prednisone was administered daily during the entire treatment period. Twenty-six of 60 patients were treated for a total of eight courses and 34 of 60 for 12 courses. RESULTS: A total of 45 patients (75%) achieved a complete response (CR), 10 (17%) a partial response (PR), and five (8%) no response. So far, 20 of 45 CR patients have relapsed, four of 10 PR patients have progressed, and three patients have died while in CR. Twenty-eight patients are still alive and responding (22 CRs, six PRs) after a median follow-up of 25 months. The projected overall survival (OS), disease-free survival (DFS), and event-free survival (EFS) rates at 2 years were 64%, 57%, and 55%, respectively. The outcome of patients treated with eight courses was similar to that of those who received 12 courses of P-VABEC in terms of CR rate and actuarial curves of OS, DFS, and EFS. Hematologic toxicity was mild in all patients. CONCLUSION: The P-VABEC regimen is active, well tolerated, and one of the briefest first-line chemotherapy regimens so far reported in the treatment of elderly patients with aggressive NHL. However, prospective randomized trials are needed to establish the real advantage of this regimen compared with other standard chemotherapy regimens.

Actuarial Analysis↗

Secretion of matrix metalloproteinases by human endometrial cells in vitro.

At each menstrual cycle, the uterine endometrium undergoes intense remodelling. Of the many factors implicated in tissue remodelling, the matrix metalloproteinases (MMPs) play a central role owing to their capacity to degrade the extracellular matrix. The aim of this study was to examine the nature and cellular origin of endometrial proteases as evaluated in culture systems with clearly characterized cell types. Endometrial cells from hysterectomy specimens were prepared using collagenase digestion. Bone-marrow-derived cells (a known source of proteases) were removed by immunopurification. Cells were cultured on different substrates (matrigel, agarose, glass or plastic). Purity of cell preparations was examined by immunocytochemistry, and proteases were characterized by zymography on SDS-PAGE containing gelatin. The cell phenotype in culture was largely influenced by the type of substrate. Gelatin-degrading enzymes detected in culture supernatants of stromal and epithelial cells had molecular masses ranging from 42 to 248 kDa, and were identified as metalloproteinases. We conclude that human endometrial stromal and epithelial cells express several matrix metalloproteinases, the expression of which clearly depended on the purity of cell preparation, on cell adhesion and on the nature of the substrate on which the cells grew. These enzymes might be involved in endometrium remodelling, blastocyst implantation and trophoblast invasion.

Cells, Cultured↗

Prognostic value of the histologic classification of peripheral T-cell lymphoma: a clinico-pathologic study of 71 HTLV-1 negative cases.

The histologic and clinical features of 71 cases of peripheral T-cell lymphoma (PTCL) have been studied. All patients were HTLV-1 negative. The T-cell phenotype was demonstrated by immunohistochemistry on cryostat sections (41 cases) and paraffin-embedded sections (30 cases). All cases were histologically classified according to the updated Kiel classification of non-Hodgkin's lymphoma (low and high-grade) and according to a Working Formulation (WF)-based classification (predominantly small cells, mixed small and large cells, and predominantly large cells). Most cases were in the high-grade group according to both classifications. The prognostic value of these two classifications was comparatively assessed. The analysis of the actuarial survival curves showed that, by using the updated Kiel classification, low-grade PTCL had a survival probability higher than high-grade PTCL although the difference was not statistically significant. Similar results were obtained when the WF-based classification was applied: furthermore, actuarial survival curves of mixed small and large cell PTCL, and of large cell PTCL were rather similar, thus indicating that differentiating these two categories has a limited prognostic value.

Adolescent↗

[Intrathoracic meningocele. A case report and review of the literature].

In this article the Authors describe a case of intrathoracic meningocele. That was diagnosed in a young asymptomatic woman after surgical resection. After a complete and accurate review of the literature, the Authors underline the rarity of the find while they also note the association of this pathology with Von Recklinghausen's neurofibromatosis. They also discuss etiology and clinical diagnostic aspects as well. In conclusion the Authors insist that with new diagnostic imaging techniques available today it is possible to accurately diagnose this disease preoperatively in most patients. This fact along with improved therapeutic regimens makes surgical excision almost free from the complications that were at one time observed.

Adult↗

F-MACHOP in advanced aggressive lymphoma.

The results of our ten years experience indicate that F-MACHOP, conceptually designed to exploit cell kinetic and synergistic principles, is an effective regimen with acceptable toxicity in a large proportion of adults with advanced stages of diffuse large cell or small non-cleaved cell lymphoma. More than 60% of all treated patients all expected to achieve long-term EFS. Patients achieving CR within 3 courses have a very high chance of being cured of their disease and do not require, in our opinion, intensification with other regimens. On the other hand the identification of a group of patients with poorer outcome (i.e. those failing to achieve an early CR) enabled testing of the potential efficacy of superintensive salvage regimens. Together with other 6 Italian hematologic institutions, we have recently participated in a prospective comparative randomized trial in which F-MACHOP was compared to MACOP-B in adults with advanced stages of diffuse large cell or small non-cleaved cell lymphoma. The preliminary results of this trial appear to confirm that F-MACHOP is an effective and tolerable regimen in such patients and there is a suggestion that its efficacy is superior to that of MACOP-B. This trial was closed to accrual in September 1991 and we look forward to the first complete analysis in March 1992.

Actuarial Analysis↗

Alpha-interferon therapy in a case of probable progressive multifocal leukoencephalopathy.

Probable progressive multifocal leukoencephalopathy (PML) was diagnosed on the basis of clinical picture and magnetic resonance imaging in a 63-year-old man with a complete remission of a non-Hodgkin's lymphoma. After the introduction of intramuscular alpha-interferon therapy, his neurological state and MRI findings showed a clear improvement. Eighteen months after the onset of first symptoms the patient has significantly recovered from both aphasia and motor impairment, and shows only a mild attentional deficit.

Antineoplastic Combined Chemotherapy Protocols↗

Prognostic value of autoantibodies against erythrocytes and platelets in chronic lymphocytic leukemia (CLL).

Antiglobulin test (AT) and Dixon tests were performed in 100 patients with CLL. Thirty-five of them had Rai stages 0 or 1, 19 stage 2, 13 stage 3, and 33 stage 4. Twelve patients showed red blood cells autoantibodies (RBCAb) positivity; positivity at Dixon test (direct, indirect, or both) was observed in 74%. The presence of autoantibodies against erythrocytes and platelets did not influence survival curves, but anemia and thrombocytopenia are considered risk factors, independently of the presence of an autoimmune disorder. Nine RBCAb positive patients with positive Dixon test had the worst survival curves, 5 of these were anemic and 1 thrombocytopenic and anemic.

Aged↗

Expression of extracellular matrix-degrading metalloproteinases by cultured human cytotrophoblast cells: effects of cell adhesion and immunopurification.

In vitro, invasion of basement membrane by human trophoblast can be blocked by metalloproteinase inhibitors. The purpose of our study was to characterize these enzymes by zymography, to define their cellular origin. First-trimester cytotrophoblast cells were prepared according to the method of Kliman et al. Half of the cell suspension was further purified with an antibody to leukocyte common antigen (CD45). Cytotrophoblast cells (immunopurified or not) were incubated in Dulbecco's modified Eagle's medium on different matrices. Progesterone, total human chorionic gonadotropin, and free beta-human chorionic gonadotropin were measured in the supernatant by radioimmunoassay or enzyme immunoassays. Secreted (in the medium) and cell-bound proteases were characterized by zymography on sodium dodecyl sulfate-polyacrylamide gels containing gelatin. Cytotrophoblast cell preparations contained 12% to 34% leukocyte common antigen-positive cells before and 0% after immunopurification. Large zones of digested matrices were observed after 48 hours of culture on Matrigel or rat tail collagen but not on agarose. Cells secreted progesterone, human chorionic gonadotropin, and free beta-human chorionic gonadotropin in vitro, but no difference was observed among cells grown on different matrices or between immunopurified and nonimmunopurified cells. By zymography, seven gelatin-degrading enzymes were seen in culture supernatants and five of them were present in cell lysates. The molecular weights of these proteases ranged from 59 to 230 kd. Immunopurification eliminated three of these enzymes, so they were clearly produced by bone marrow-derived cells (leukocyte common antigen positive) contaminating the cytotrophoblast cell preparation. Cells grown on Matrigel express a unique 59 kd gelatinase that was not seen in the supernatants of cells grown on other matrices. Zymography in the presence of inhibitors showed that these enzymes were neutral metalloproteinases, which might be responsible for the observed extracellular matrix degradation.

Cell Adhesion↗

The F-MACHOP sequential combination chemotherapy regimen in advanced diffuse aggressive lymphomas: long-term results.

The present study reports the long-term results of the F-MACHOP sequential combination chemotherapy regimen in 113 adult patients with advanced stages of diffuse large-cell or undifferentiated lymphoma who were consecutively treated with this regimen from January 1980 to December 1986 at a single institution. The CR rate was 78% and 17 relapses were observed, so that 80% of CR patients are expected to be free of relapse at 5 and 10 years after a median follow-up off-therapy of 5.7 years (range 3.2-10.1). Projected survival and event-free survival at 8 years are 68% and 62%, respectively. Prognostic factor analysis indicates that the CR rate was influenced by systemic symptoms and number of extranodal sites, disease-free survival by tumor burden and number of courses to achievement of CR, event-free survival and survival by tumor mass diameter, systemic symptoms and number of extranodal sites. Toxicity was mainly hematological, and 3 patients (3%) died while severely neutropenic. The rapidity of response appears to have prognostic value, particularly in patients presenting with high tumor burden, in whom achievement of a CR within 3 courses indicates a group of patients with a very high chance of cure with this regimen.

Adolescent↗

MACOP-B vs F-MACHOP in the treatment of high-grade non-Hodgkin's lymphomas.

From September 1988 two hundred-sixty-seven (267) untreated patients (pts) with stage II to IV high grade non Hodgkin's lymphoma (NHL) have been enrolled in a multicenter, randomized, still ongoing study, comparing two third-generation combination chemotherapy regimens, MACOP-B versus F-MACHOP. At the present time, 177 pts have completed the treatment program and are evaluable, with a median follow-up of 13 months. Clinical, histologic and laboratory characteristics are equally distributed in both groups. Among the 92 pts treated with MACOP-B, 58 (63%) achieved a complete remission (CR), 17 complete responders have relapsed (29%), and 21 have died (23%), including 3 treatment-related deaths. Among the 85 pts who received F-MACHOP, 65 (76%) achieved a CR, 9 complete responders have relapsed (14%), and 11 pts have died (13%), including 3 treatment related deaths. 30 months-projected survival is 64% for MACOP-B treated pts compared to 84% for F-MACHOP treated pts; 30 months-projected relapse- free survival is 80% and 84%, respectively. F-MACHOP seems to be superior in immunoblastic lymphoma (overall survival, OS, 82% vs. 54%) and in Burkitt-type lymphoblastic lymphoma (OS 100% vs, 42%). The degree of hematological and non-hematological toxicity was similar in both regimens. More reliable conclusions will be drawn after a longer follow-up.

Adult↗

Clinical and pathological restaging in aggressive non-Hodgkin's lymphomas.

Residual tumor masses are sometimes found in non Hodgkin's lymphoma (NHL) patients after chemo-radiotherapy treatment. Radiologic findings do not differentiate lymphoma from fibrosis necrotic tissue. Surgical and histology reevaluation is the most reliable method of evaluation the viability of tumor residual masses. Sixty-three consecutive high-grade NHL were treated with F-MACHOP regimen. After 3 courses of F-MACHOP the response was evaluated clinically: twenty two (36%) achieved a clinical complete remission, 32 a clinical partial remission, 7 were non responders and two were not evaluable. An early pathological response evaluation was performed in 23 clinical partial responders. Fifteen (65%) patients had no evidence of NHL after pathological restaging and were considered as pathologic complete response and completed treatment with 3 additional courses F-MACHOP. Eight (35%), histologically positive, were defined as pathologic partial response and were crossed to salvage regimens. The 1 year actuarial event-free survival differed significantly according to clinical response after 3 courses of F-MACHOP and the outcome of clinical partial responders was highly dependent on the result of pathological restaging (87% for negative and 23% for positive). Our experience suggests that a significant proportion of clinical partial responses are histologically confirmed at pathological restaging when this procedure is performed early during treatment.

Adult↗

Bronchial reactivity and sex hormone: study in a Turner's population.

Respiratory function and bronchial reactivity was studied by carbachol challenge in 41 patients with Turner's syndrome and in 46 controls. In patients and controls the personal and family history of atopic illnesses was evaluated; reactivity to skin allergen tests was studied in patients only. Patients with Turner's syndrome had less allergy skin test reactivity; no difference was found in allergic symptoms between patients and controls despite the patients having a more positive family history of atopy (P less than 0.05). Respiratory function variables were higher in patients than in controls, and bronchial reactivity as expressed by the results of carbachol testing was higher in Turner's patients than in controls (P less than 0.01). Bronchial reactivity was significantly reduced after 6 months of estrogenic therapy (P less than 0.05) in subjects with Turner's syndrome, while the same did not occur in patients who did not receive estrogen treatment. This study of pulmonary function and bronchial reactivity in Turner's patients may help understand the effects of sex hormones in the regulation of bronchial tone and of bronchial response to constrictive agents.

Adolescent↗

[Mechanical staplers in exeresis surgery of pulmonary cancer].

Surgical stapling devices are widespread in many branches of surgery and are employed with success in thoracic surgery. Our experience is in line with that of other Authors: stapling of the bronchus is faster, does not contaminate the operative field and reduces the incidence of bronchopleural fistulas (4.76% to 1.59%). Parenchymal stapling is indicated for resection of bullae, metastases and peripheral lesions. The mechanical suture is air-tight and faster than manual suture. Pulmonary vessels may also be closed mechanically; however, we do not advocate the use of stapling devices especially in the closure of the pulmonary artery.

Aged↗

Intrathoracic lobe of the liver. Case report and review of the literature.

A case of a heterotopic intrathoracic lobe of the liver connected through a normal diaphragm to the main organ by a vascular and biliary pedicle is described. Eight similar cases reported in the literature are reviewed and a comparative evaluation is undertaken to elucidate the correct clinical diagnosis and the indications for operative exploration. Because the occurrence of ectopic supradiaphragmatic hepatic tissue should be considered, it is believed that the preoperative evaluation of a solid, smooth lump in the diaphragmatic region should include gallium liver scans prior to invasive procedures.

Adult↗