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Biomedical subjects

U Tirelli

Publications and source records attributed to U Tirelli.

At least 271 records · Page 15Linked to original sources

Malignant tumors other than lymphoma and Kaposi's sarcoma in association with HIV infection.

Since 1981 there has been a constant rise in the incidence of squamous cell carcinoma of the oral cavity and the anorectum among homosexual men in the United States. In addition, lung cancer, testicular cancer, chronic lymphocytic leukemia, malignant melanoma, basal cell carcinoma, cervical cancer, and multiple myeloma have been recently reported in persons at risk for AIDS with HIV infection, with some peculiar clinicopathological features, including age, histological type, and clinical aggressiveness. Within the GICAT (Gruppo Italiano Cooperativo AIDS & Tumori) framework, we have identified four cases of testicular cancer, two cases of leukemia, and 1 case each of cervical cancer, carcinoma of the oral cavity, lung cancer, brain tumor, and multiple myeloma in persons at risk for AIDS, mainly i.v. drug abusers, with HIV infection, diagnosed in different Italian institutions. Work is in progress in order to collect histological and clinical data on these tumors. Although these data are preliminary and are not indicative of an actual increase in the incidence of malignancies other than malignant lymphomas and Kaposi's sarcoma in the AIDS setting, clinicians should be aware of the possible association of these tumors with HIV infection.

Acquired Immunodeficiency Syndrome↗

Splenic irradiation in chronic lymphocytic leukemia. A 10-year experience at a single institution.

A group of 38 patients with a median age of 70 years and chronic lymphocytic leukemia (CLL) were treated using a cobalt 60 U or a 6-MeV linear accelerator. A direct field or two opposite fields covered the palpable spleen area in most patients. 100 cGy were administered weekly for a total dose of 10 Gy, given over 10 weeks. The stage arrangement (according to Rai) for the 32 evaluable patients was as follows: Stage I: 11 patients, Stage II: nine patients, Stage III: three patients, and Stage IV: nine patients. Patients in Stages I and II were treated when symptomatic. Twenty-five patients (78%) achieved hematologic response (HR), defined as normalization of the differential leukocyte count, of the total blood cell count, and of bone marrow infiltration. However, no complete response according to the standard criteria of response has been obtained. The median response time of HR was 7 months (range, 1.5 months to greater than 120 months). The overall median survival time from the start of splenic irradiation (SI) was 40 months. More than 50% splenomegaly reduction was obtained in 63% of patients, whereas no benefit was verified in the lymphadenopathy. The incidence of second tumor was 29%. Fourteen patients benefited from a further 21 SI cycles. SI does not result in a complete remission and therefore cannot modify the course of CLL. This treatment is most advisable for elderly patients with predominant bone marrow lymphocytosis, for patients with previous extensive chemotherapy or radiotherapy, and for patients with poor marrow reserve. Moreover, because of the absence of toxicity subsequent treatment is not compromised.

Aged↗

Reed-Sternberg cells and their cell microenvironment in Hodgkin's disease with reference to macrophage-histiocytes and interdigitating reticulum cells.

Fifty-eight paraffin-embedded lymph node biopsies from patients with Hodgkin's disease (36 nodular sclerosis, 14 mixed cellularity, five lymphocyte depletion, and three lymphocyte predominance) were immunostained with a panel of monoclonal (anti-Leu-M1, antileukocyte common antigen) and polyclonal (to lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, and S-100 protein) antibodies by using the avidin-biotin immunoperoxidase technique. Both the immunostaining features of the Reed-Sternberg (R-S) cells and their variants, and the numbers of immunostained accompanying cells morphologically corresponding to macrophage-histiocytes (M-H) and to interdigitating reticulum cells (IRC) were analyzed. Variable numbers of R-S cells and their variants were positive for Leu-M1 in 83% of the cases, for alpha 1-antitrypsin in 40%, for alpha 1-antichymotrypsin in 30%, and for leukocyte common antigen in 3.4%; they were constantly negative for lysozyme and S-100 protein. Whereas the average numbers of accompanying cells immunostained for Leu-M1 were very low, the numbers of S-100-positive IRC were relatively high in all the Hodgkin's subtypes. The average numbers of M-H were lower (P less than 0.1 for lysozyme; P less than 0.001 for alpha 1-antichymotrypsin) in the nodular sclerosis than in the other pooled subtypes. In the nodular sclerosis subtype, however, R-S cells and their variants that stained positive for Leu-M1 appeared to express more frequently the lineage markers of M-H (alpha 1-antitrypsin and/or alpha 1-antichymotrypsin). These data appear to suggest that there is not an apparent qualitative correspondence between the immunostaining features of the cellular microenvironment composed of M-H and IRC and the features of the R-S cells.

Antigens, Differentiation, T-Lymphocyte↗

Practical importance of routine paraffin-embedded bone marrow biopsy in multiple myeloma.

Paraffin-embedded bone marrow biopsy specimens obtained prior to (37) or after (25) therapy from 62 patients with multiple myeloma (MM) were analyzed with particular reference to infiltration pattern, extent of infiltration, and myeloid to myeloma tissue percentage ratio (MMR) to verify their mutual relationships and clinicopathologic relevance. Fifty-nine biopsies were evaluable for infiltration pattern (diffuse in 27, interstitial in 25, and nodular in 7). Diffuse and interstitial patterns were more common (P less than 0.025) in stage III and stage I patients, respectively. A higher (P less than 0.001) mean serum paraprotein level was found in patients with the diffuse pattern than in those with the interstitial pattern. The average extent of infiltration by myeloma cells in the residual myeloid tissue was higher (P less than 0.001) and a high extent (75% or more) was more frequently (P less than 0.005) seen in diffuse than in interstitial pattern cases. The average MMR value was lower (P less than 0.001) and a MMR value less than 1 was more frequently (P less than 0.005) seen in the diffuse pattern group than in the interstitial pattern group. All these differences were present also when a separate analysis was performed for treated and untreated patients. It seems that a diffuse histologic pattern, as opposed to interstitial, would significantly predict a bone marrow extent of infiltration of 75% or more, a MMR lower than 1, a higher serum paraprotein level, and a clinical stage III. Bone marrow biopsy appears thus to play a role in providing parameters of prognostic relevance in MM also in the course of the disease. Prospective studies are needed to establish whether histologic pattern has an independent prognostic value.

Biopsy↗

Phase II study of esorubicin (4'-deoxydoxorubicin) in locally advanced or metastatic head and neck carcinoma.

Sixteen patients with locally advanced or metastatic head and neck cancer were treated with esorubicin (4'-deoxydoxorubicin) at a dose of 30-35 mg/m2 i.v. every 3 weeks. One patient was lost to the follow up after one cycle, whereas in the 15 evaluable cases a total of 34 courses were administered (median per patient: 2, range: 1-6). Pretreatment for parameter lesions consisted of radiotherapy in 5, chemotherapy in 3 and both treatments in 1 patients respectively. Overall, one partial response, one stable disease and 13 progressions were documented. Severe (grade 3 and 4) leukopenia, thrombocytopenia and anemia were noted in 3, 1 and 1 patients respectively. The only patient developing leukopenia and thrombocytopenia of grade 4 subsequently died because of pneumonia. On the other hand, non-hematologic toxicity was generally mild. At this dose and schedule, esorubicin demonstrated an activity less than 20% in head and neck cancer and therefore, no further evaluation is warranted.

Aged↗

Pharmacokinetics of 7-con-O-methylnogarol in patients with solid tumors.

The pharmacokinetics of 7-con-O-methylnogarol were investigated by HPLC assay with fluorometric detection in nine cancer patients with normal hepatic and renal function, after a 2-h infusion of 160 or 200 mg/m2. The drug disappeared from plasma biexponentially with a mean elimination half-life of 38 +/- 3 h; the mean apparent volume of distribution and the plasma clearance were 805 +/- 91 1/m2 and 14 +/- 2 1/h per m2. Within 48 h of administration, urinary excretion of the drug and its metabolite 7-con-O-methyl-N-demethylnogarol accounted for 2%-15% and 0.1%-6% of the dose, respectively. Neither 7-con-O-methylnogarol nor its N-demethyl derivative was conjugated with glucuronic acid or sulfate in detectable amounts.

Aged↗

Pharmacokinetics of VM 26 given intrapericardially or intravenously in patients with malignant pericardial effusion.

Three patients with lung cancer (1 SCLC, 2 NSCLC) and pericardial malignant effusion received 100 mg/m2 Teniposide (VM 26) i.v. and, 1 week later, 50 mg/m2 intrapericardially. Plasma, pericardial, and urine levels of the drug were measured in all patients after the two treatments by a HPLC assay. After intrapericardial administration, a high VM 26 concentration was found in the pericardial cavity and slow systemic drug absorption was observed. Since the drug AUC after intrapericardial administration was approximately 15-21 times that after i.v. administration, it could be that this treatment is more effective against neoplastic deposits localized in the pericardium. Even though this small series does not permit conclusions to be drawn on the efficacy of VM 26 given intrapericardially, the lack of local toxicity, minimal systemic toxicity, and the response observed in two out of three patients given intrapericardial VM 26 suggest that further investigation should be carried out on this method of VM 26 administration.

Aged↗

Non-Hodgkin's lymphomas in the elderly: prospective studies with specifically devised chemotherapy regimens in 66 patients.

The results of 2 consecutive and prospective trials with specifically devised chemotherapy regimens in elderly patients (pts) with non-Hodgkin's lymphoma (NHL) are reported. Between August 1979 and September 1984, 66 pts aged 70 or older (median 75 years) with NHL entered 2 consecutive trials, the former with single agent teniposide 100 mg/m2 i.v. weekly (41 pts), the latter with etoposide and prednimustine (E + P), 100 mg/m p.o. for 5 days every 21 days (25 pts). Forty-five pts were previously untreated, 21 previously treated. Forty-seven pts were of the intermediate and high grade groups according to the Working Formulation; 19 pts were of the low grade; 57 pts were stages III and IV, 9 pts were stages I and II. The median performance status was 70 (range 30-100). The objective response rate in the 66 evaluable pts is 53% with 38% CR; the 3-year overall, disease-free and CR survivals are 21, 12 and 40% respectively. The objective response rate in the 45 previously untreated pts is 58% with 42% CR; the 3-year overall, disease-free and CR survivals are 24, 16 and 58% respectively. The overall toxicity was mild. Severe toxicity (grade III and IV according to WHO criteria) was observed only in 16/498 courses (3.2%), with 1 toxic death (grade IV leucopenia). We experienced the usefulness of a properly orientated clinical approach to elderly pts with NHL. We suggest that a combination regimen like E + P, suitable for oral administration, may be safely employed in a large fraction of pts with NHL.

Aged↗

A phase II study of AMSA in head and neck cancer.

AMSA was given to 22 evaluable patients with advanced head and neck cancer with measurable lesions. The starting dose was 90-120 mg/m2 by i.v. infusion over 45 min every 3 weeks. The dose of AMSA was escalated by 30 mg/m2 in absence of bone marrow toxicity. At least two cycles were given prior to the evaluation of response. Only one patient with oropharyngeal cancer achieved a partial response, lasting for 20 weeks. Toxicity was mild and mainly hematological. We conclude that AMSA given at this dose and schedule has little activity in head and neck cancer.

Adult↗

Selective reduction of the OKT 4 positive 4B4 positive subset during HTLV III infection in humans.

Combinations of monoclonal antibodies defining the OKT 4 positive lymphocyte subset in the peripheral blood of intravenous drug abusers suggest that the 4B4 positive helper inducer population is greatly reduced in subjects infected with HTLV III. No differences were seen instead using different antibodies directed against various epitopes of the T4 molecule. These results suggest that the multiple marker assay could be very useful to define immunological status during HTLV III infection in humans.

Acquired Immunodeficiency Syndrome↗

S-100 protein, fibronectin, and laminin immunostaining in lymphomas of follicular center cell origin.

Forty-nine paraffin-embedded biopsy specimens of involved nodal and extranodal tissue (bone marrow, spleen, and liver) from 13 patients with follicular center cell lymphomas (FCCL) and 14 with small lymphocytic lymphomas (SLL), including 11 cases with chronic lymphocytic leukemia, were tested for S-100 protein immunoreactivity. Analysis for fibronectin and laminin immunoreactivities was limited to the lymph node biopsy specimens. In FCCL, S-100-positive dendritic reticulum cells (DRCs) were found in 23 of the 26 tissue specimens examined, regardless of the involved sites and the growth pattern. Cases with completely or predominantly follicular pattern were usually associated with a spherical meshwork pattern of S-100-positive DRCs; in the FCCL specimens with a diffuse pattern (lymph nodes and bone marrow) as well as in the specimen areas with a minimally follicular tumor pattern, S-100-positive DRCs were consistently fewer in number and composed loosely aggregated nests. No S-100-positive DRCs were found in all the biopsy specimens in SLL. Concerning fibronectin and laminin immunostainings, results showed that no differences were present between areas of follicular and diffuse neoplastic growth and that the neoplastic growth of FCCL maintained for each antiserum the same distribution pattern as that seen in normal follicles. Analysis of the microenvironmental components as revealed with antisera used in the current study--particularly with anti-S-100 protein antiserum--appears to be a useful adjunct for the identification of FCCL in paraffin-embedded biopsy specimens, especially in extranodal sites.

Dendritic Cells↗

Immunohistochemical, enzyme histochemical, and immunologic features of giant lymph node hyperplasia of the hyaline-vascular type.

A combined histologic, immunohistologic, enzyme histochemical, and immunologic study has been carried out in a 7-year-old girl with recurring extramediastinal monocentric giant lymph node hyperplasia of hyaline-vascular type. A large panel of monoclonal and polyclonal antibodies to lymphoid and nonlymphoid cell markers were tested on frozen and paraffin-embedded lymph node tissue as well as on cell suspension and peripheral blood. Tissue enzyme histochemical study, including a conventional hematologic panel, was performed on frozen and plastic-embedded sections. The pattern was dominated by nodular aggregates of round BA-1+ Leu-14+ HLA-DR+ ATPase+ lymphocytes with polyclonal sIgD and sIgM positivity and lacking cIg and BA-2 staining. Leu-1+/Leu-4+, OKT6+, OKT10+, Leu-7+, and CALLA+ cells were few or absent in the nodules, whereas DRC-1+ BA-2+ HLA-DR+ 5'-Nuc+ cells formed a dendritic network in the outer portion of the nodules. No immunoreactivity for lymphoid and nonlymphoid cell markers, including cytokeratin and keratin, was detected in centrinodular histiocytic-like cells. Particularly, the Hassall's-like structures contained a target-like positivity for laminin, and consisted of flattened acid phosphatase (AP), alpha-naphthyl acetate esterase (ANAE), 5'-nucleotidase (5'-Nuc), and adenosine triphosphatase (ATPase) positive cells, whose enzyme profile overlapped with that of the histiocytic-like cells. The extranodular areas were mainly composed of Leu-1+/Leu-4+ lymphocytes with Leu-3a+/OKT4+ phenotype and, to a lesser extent, of OKT6+ OKT10+ lymphoid cells and scattered cells with markers of histiocytic lineage. The abundant vascular component was generally identified by laminin positivity and, in smaller proportion, it was positive for Factor VIII-related antigen. Most of the medium-sized vessels with high endothelium had marked AP, ANAE, and ATPase activities. The process observed resulted from vascularized nodular aggregates of nontransformed B-cells with the phenotype of primary follicle lymphocytes, associated to centrinodular histiocytic-like cells with a distinct enzyme profile.

Antibodies, Monoclonal↗