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Biomedical subjects

S Monfardini

Publications and source records attributed to S Monfardini.

At least 145 records · Page 8Linked to original sources

Immunoglobulin and T cell receptor gene rearrangements and in situ immunophenotyping in lymphoproliferative disorders.

We investigated for rearrangements of the immunoglobulin (Ig) heavy and light chain genes and of the T cell receptor gamma (TCR gamma) and beta (TCR beta) genes 45 biopsy samples from a variety of lymphoproliferative disorders. They were diagnosed histopathologically and immunophenotypically as non-Hodgkin's lymphomas (NHLs) of the B cell type (19 cases), NHLs of the T cell type (3 cases), NHLs of "undetermined" cell type (3 cases), atypical lymphoid proliferation (1 case) and AIDS-related lymphadenopathies with florid polyclonal follicular hyperplasia (19 cases). A monoclonal proliferation of B cells was shown by DNA analysis in all 19 B cell NHLs. In two immunohistologically determined T cell NHLs (both diagnosed as mycosis fungoides) the cells had rearrangements of TCR beta gene, whereas in the third case (lymphoblastic NHL) the cells had rearrangements of Ig heavy chain and TCR gamma and TCR beta genes. None of the B cell NHLs exhibited TCR gamma and TCR beta gene rearrangement bands. All the "undetermined" cell NHLs demonstrated rearrangements of Ig heavy chain gene associated with the germ line TCR gamma and TCR beta genes; in two cases light chain gene rearrangements were also found. The atypical lymphoid proliferation, in which the differential diagnosis was between a reactive or malignant process, and two out of 19 cases of florid polyclonal follicular hyperplasia showed a clonal B cell population by DNA analysis. This study indicates that there was a strong correlation between the rearrangements of specific genes and the immunophenotype of the NHL; moreover, DNA analysis of tissue biopsy specimens from phenotypically "undetermined" cell NHLs and from equivocal lymphoid proliferation using Ig and TCR gene probes yielded an answer in the cases analyzed. The significance of clonal B cell expansions found in two AIDS-related lymphadenopathies should be interpreted with caution.

AIDS-Related Complex↗

Buserelin treatment of advanced prostatic cancer: a phase II study.

From August 1986 to September 1988, 76 eligible patients with advanced prostatic carcinoma, measurable or evaluable disease, no previous hormonal treatment, were treated with Buserelin at a dosage of 500 micrograms every 8 h for 7 days, followed by 400 micrograms intranasally three times a day. No concomitant antiandrogens were administered. In the 63 evaluable patients (11 patients not yet evaluable because of short treatment time, two lost to follow-up), three complete remissions, 28 partial remissions, 30 stable disease and two progressions were obtained (National Prostatic Cancer Project criteria). Median duration of response was 55+ weeks. Side effects were modest, mostly related to the endocrinological effects of Buserelin. Transient increase in serum testosterone levels was found in 37% of the evaluable patients, but transitory 'flare-up' was present in seven patients only. With a median follow-up time of 11.5 months, median survival has not been reached. In conclusion, this study confirmed the activity of Buserelin and the feasibility of its middle-term administration.

Aged↗

Unusual malignant tumours in 49 patients with HIV infection.

Between December 1986 and December 1988, the Italian Cooperative Group on AIDS-Related Tumours documented 49 HIV-related tumours other than malignant lymphomas (ML) and Kaposi's sarcomas (KS), predominantly among HIV-infected intravenous drug abusers (IVDA). Of 12 germinal testicular tumours collected, six were seminomas, two of which were pure embryonal and the other four embryonal mixed. Cervical carcinoma was observed in nine IVDAs (intraepithelial in eight and advanced, with rapid progression, in one). Lung cancer associated with HIV infection was reported in eight patients, of whom four had an adenocarcinoma, two a small cell carcinoma, one an epidermoid carcinoma and one a mesothelioma. All patients with non-small-cell-lung cancer (SCLC) were at stage III, while those with SCLC and mesothelioma had limited disease. Five out of eight presented with limited disease at onset. The median age was low; lung cancer occurred predominantly in young adults, of whom all but one were smokers. Three patients could not be treated; four died while on treatment because of progression of the neoplasia and one died of an overdose. Acute lymphoblastic leukaemia (ALL) was diagnosed in five patients. The immunophenotype was always Burkitt-like (L3), and acute myeloblastic leukaemia (M2) was diagnosed in one. Of the central nervous system (CNS) tumours, two cases of glioblastoma and one of medulloblastoma were described. Two cases of young adults with multiple myeloma and two cases of colorectal carcinoma were also reported. One case of chronic lymphocytic leukaemia, one anorectal carcinoma, one oral carcinoma, one pancreatic carcinoma, one thymoma, one kidney carcinoma, one malignant melanoma and thyroid carcinoma were also found.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Low-dose aminoglutethimide plus steroid replacement in advanced breast cancer patients resistant to conventional therapies.

In an attempt to define the activity and toxicity of low-dose aminoglutethimide plus steroid replacement in advanced breast cancer, we treated 40 patients with aminoglutethimide 500 mg/day + hydrocortisone 50 mg/day. Previous treatment consisted of additive hormones in 29 patients, oophorectomy in 8, and chemotherapy in 32. Among the 37 patients evaluable for response and toxicity, 5 objective responses (16.2%) and 20 stable diseases (54%) were noted. Toxicity, absent in 23 patients (62.1%) and mild in 14, consisted mainly of Grade I (WHO) nausea, drowsiness, cutaneous rash, and dizziness. Responders and patients with stable disease experienced a similar survival (median not reached at 22 months). Aminoglutethimide at low doses appears to be beneficial in patients refractory to conventional therapies even if the objective response rate is low.

Adult↗

Chemotherapy of advanced head and neck squamous carcinoma with cisplatin, fluorouracil and bleomycin administered in an outpatient schedule.

From May 1983 to September 1984, 48 consecutive patients with locally advanced, recurrent and/or metastatic head and neck squamous carcinoma were treated with cisplatin 60 mg/m2 i.v. on day 1, fluorouracil 10 mg/kg i.v. push from day 1 to day 4 and bleomycin 10 mg/m2 i.v. from day 1 to day 4, every 3 weeks. In the 44 evaluable patients complete remission was observed in 4, partial remission in 9, stable disease in 19, and progression in 12, for a 29.5% response rate. When the analysis was limited to the 21 patients with PS greater than 70 and no previous chemotherapy or radiotherapy, the response rate was 48%. Toxicity was acceptable, and no treatment related deaths occurred. Overall median survival (all eligible patients) was 7 months. Although further studies with this combination in poor risk patients (previously treated or with PS less than 70) do not appear to be indicated, a more accurate assessment in good risk patients might be warranted.

Adult↗

Presidential address at the European Society for Medical Oncology, Nice, 30 November 1986.

Medical oncology is now accepted in Europe as a branch both of internal medicine and of clinical oncology. In this article the present situation of this discipline is analysed with reference to the plateau in the results achieved in chemosensitive tumours and to the small effect of chemotherapy in tumours considered to be "big killers". Although new avenues in tumour biology do not necessarily mean therapeutic success in the near future, at present basic discoveries are being developed for clinical therapy faster than before. Besides biological response modifiers, the development of new drugs should receive constant attention from medical oncologists. This attitude has persisted despite an awareness that the political community has had little interest in the allocation of funds for the development of new anticancer agents. Clinical trials have recently been subjected to some criticism. But unless large multicentre trials are continued with better quality control and organization it will not be possible to provide adequate resources for the many and various new drugs and biological response modifiers expected to enter the field in the next few years. The active involvement of medical oncologists in controlled clinical trials should then continue. Finally, the task and achievements of the scientific society, which allows close contacts among European medical oncologists, are briefly underlined.

Antineoplastic Agents↗

Phase II study of iproplatin (CHIP, JM-9) in advanced testicular cancers progressing after prior chemotherapy.

Twenty-two patients with advanced testicular cancer received iproplatin at a dose of 180-240 mg/m2 every 4 weeks. All the patients progressed or recurred after chemotherapy including cisplatin. The most severe toxicity was thrombocytopenia with two toxic deaths after a first cycle of 240 and 180 mg/m2 respectively. Nausea and vomiting were almost universal but mild in intensity. One renal failure occurred 6 weeks after the first cycle while the tumor was progressing. No antitumor activity was observed in this heavily pretreated population of patients.

Adult↗

Iproplatin and carboplatin induced toxicities: overview of phase II clinical trial conducted by the EORTC Early Clinical Trials Cooperative Group (ECTG).

Data of five phase II clinical trials on iproplatin and carboplatin, conducted by the ECTG, have been pooled in order to evaluate the extent of toxicities of these compounds. One hundred and seventy patients treated with iproplatin and 65 patients treated with carboplatin were evaluable. Most of them (81%) had been previously treated with chemotherapy. Doses ranged from 180 to 300 mg/m2 every 4 weeks for iproplatin, and from 350 to 450 mg/m2 every 5 weeks for carboplatin, according to the initial status of the patient. WHO criteria were used to grade toxic effects. Weekly blood counts were performed, and lowest observed counts were analysed by non-parametric methods. Censored data were analysed by actuarial methods. Thrombocytopenia was the dose-limiting toxicity and was dose related. Leucopenia was less severe. The risk of thrombocytopenia varied largely amongst patients, and could be predicted from the initial platelet count, the initial creatinine level and prior therapy with alkylating agents. The cumulative risk increased with the total dose, but with a decreasing hazard rate, and without additional delay to platelet recovery. Nausea, vomiting and diarrhoea were the most frequently observed non-haematological side-effects, and were more severe with iproplatin than with carboplatin. Peripheral neuropathy was observed in some cases, but could be due to prior treatments. Renal toxicity did not cause major problems. Our results confirm the findings of the phase I trials: thrombocytopenia is dose-limiting for both drugs, and renal side-effects are negligible. The risk model of thrombocytopenia, consistent with Egorin's model for carboplatin, could serve as a basis for dose adjustment. The feasibility of the scheme could be insufficient for prolonged treatment.

Adult↗

Risk factors for HIV infection in drug addicts from the northeast of Italy.

Prevalence and determinants of HIV infection were assessed in 313 parenteral drug addicts admitted to five Centers for Drug-Addict Assistance and two prisons located in the northeast of Italy (Friuli Venezia-Giulia), an area some distance from the major Italian cities first reached by the AIDS epidemic. The overall prevalence of HIV positivity was also rather high in this area, ie 30% with 24-36% confidence interval. The most important risk factors (besides syringe sharing applicable to all drug addicts), turned out to be of a geographical nature, ie living in Pordenone province (where a US military base is located) or coming from other endemic areas and having travelled long distances in the past three years. Prostitution also seemed to increase the risk of infection, but duration of drug addiction had little effect. In addition to persistent generalized lymphadenopathy (closely linked to HIV infection), reversal of helper:suppressor T-cell ratio was found in 67% of HIV positive individuals, but also in 31% of HIV negative ones. Clinical signs and symptoms strongly linked with HIV positivity were fatigue, weight loss, splenomegaly, fever and nocturnal sweats.

Adolescent↗

Cisplatin and etoposide as second-line chemotherapy in patients with small cell lung cancer.

Twenty-seven evaluable patients with small cell lung cancer (SCLC) resistant to, or relapsed after induction combination chemotherapy (CT) were treated with etoposide (VP16) plus cisplatin (DDP). Previous treatment was: alternating CT with cyclophosphamide (C), adriamycin (A), methotrexate (M), procarbazine (P) (CAMP)/VP16, BCNU (B), hexamethylmelamine (H) (VP16 BH) in 16 patients; C, A, vincristine (CAV) in 6 patients; C, A, and VP16 (CAVP16) in 5 patients. We observed 2 (7%) complete responses (CR) and 9 (33%) partial responses (PR). Duration of CRs was 8 and 14 weeks, respectively. PRs lasted a median of 22 weeks (range 16-44). Seven of 21 (33%) patients previously treated with VP16 responded to DDP plus VP16 (D-V). These results confirm D-V regimen as active in SCLC patients even when heavily pretreated. Our 33% response in patients who had VP16 in their induction treatment regimen provides further evidence of an important potentiating effect of DDP, as reported in animal system.

Antineoplastic Combined Chemotherapy Protocols↗

Clinical and laboratory findings at presentation in persistent generalized lymphadenopathy vs malignant lymphoma.

The purpose of this study is to compare the clinical and laboratory findings at presentation of 38 intravenous drug abusers with pathologically documented persistent generalized lymphadenopathy and 50 patients with biopsy proven malignant lymphoma (30 Hodgkin diseases, 20 non-Hodgkin's lymphomas) not related to acquired immunodeficiency syndrome, all aged 40 years or less and consecutively seen and evaluated with a similar clinicopathological approach since May 1984 in a single institution, Centro di Riferimento Oncologico, Aviano, Italy. Our results document that, although pathology is the decisive diagnostic tool, selected clinical and laboratory findings may contribute to a better differentiation of persistent generalized lymphadenopathy from malignant lymphoma not related to acquired immunodeficiency syndrome. Therefore, young patients presenting with generalized lymphadenopathy, apparently not related to known groups at risk for acquired immunodeficiency syndrome, should be evaluated also according to a protocol which includes the detection of symptoms, signs, and laboratory data that are known to be significantly increased among patients with persistent generalized lymphadenopathy.

Adult↗

Malignant lymphomas in patients with or at risk for AIDS: a report of 50 cases observed in Italy.

For the first time the presence of a consistent number of malignant lymphomas among persons at high risk for AIDS has been documented in Italy. The majority of our cases started to occur in 1983, in line with the trend for a 2-year delay in the spread of the epidemic of AIDS in Europe. The patients with non-Hodgkin's lymphomas had an increased incidence of high grade subtypes, particularly of the Burkitt type, and were in an advanced stage with frequent extranodal involvement. Patients with Hodgkin's disease had a lower incidence of extranodal localization in comparison with the North American series. American patients with malignant lymphomas were reported to be predominantly homosexual; in contrast, the Italian cases were mostly drug addicts. The occurrence of malignant lymphomas was also correlated in Italian patients as well as in American patients with a shorter survival time, when compared with malignant lymphomas occurring in the same age group of the general population.

Acquired Immunodeficiency Syndrome↗