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Biomedical subjects

P Mazza

Publications and source records attributed to P Mazza.

At least 91 records · Page 5Linked to original sources

Phase III comparative trial (m-BACOD v m-BNCOD) in the treatment of stage II to IV non-Hodgkin's lymphomas with intermediate- or high-grade histology.

From September 1984 to July 1986, 70 previously untreated patients with Stage II to IV intermediate- or high-grade non-Hodgkin's lymphoma (according to the International Working Formulation) were enrolled in a phase III comparative trial. The objectives of the study were to compare the efficacy and safety of using mitoxantrone instead of doxorubicin in the combination chemotherapeutic regimen m-BACOD (intermediate-dose methotrexate, bleomycin, Adriamycin [doxorubicin, Adria Laboratories], cyclophosphamide, Oncovin [vincristine, Eli Lilly and Company], and dexamethasone). Seventy patients were randomly assigned to receive either m-BN (Novantrone; mitoxantrone, American Cyanamid Company) COD or m-BACOD. The complete-response rate was 57% in both treatment groups, and no significant differences in overall or relapse-free survival were recorded between the two groups. Patients treated with m-BACOD experienced severe alopecia more frequently (P less than .001) and reported six adverse cardiac events of grade greater than 1 whereas neither was observed among those receiving m-BNCOD. The mitoxantrone-containing regimen was found to have an equivalent efficacy and reduced clinical toxicity in comparison to the standard doxorubicin-containing regimen in patients with poor-prognosis non-Hodgkin's lymphomas.

Adult↗

Effect of salbutamol on potassium influx in erythrocytes of allergic subjects and investigation of beta 2 receptor autoantibodies.

Recent experimental and clinical reports have demonstrated that beta-adrenergic blockade impairs and beta-adrenergic stimulation enhances in vivo extrarenal potassium uptake in man. In some allergic patients extrarenal potassium disposal in vivo was reduced compared with normal subjects. In the present study we report that in vitro salbutamol induced potassium uptake by red blood cells may be reduced in some atopic patients. By using a ligand binding assay on cultured human A431 cells, we tried to determine whether in the sera of these atopic subjects there could be anti beta-adrenergic receptor autoantibodies. The results suggest that the observed reduced response to salbutamol of atopics' red blood cells does not depend on autoantibody activity.

Adrenergic beta-Agonists↗

Biological studies on 1,2-benzisothiazole derivatives. III. Evaluation of antibacterial, antifungal and DNA-damaging activities of 1,2-benzisothiazolin-3-ones.

The in vitro evaluation of the antibacterial, antifungal and DNA-damaging properties of some 1,2-benzisothiazolin-3-one derivatives is described. Antibacterial activity against Gram+ microorganisms (Bacillus subtilis and Staphylococcus aureus) was demonstrated in some N-alkoxybenzyl, N-aryl and N-alkoxyphenyl derivatives. Antifungal activity turned out to be strongly affected by the substituents considered. Some derivatives exhibited selective activity against the fungi used. Poor antimicrobial activity was observed in the N-chlorocarbonylphenyl and N-carboxyamidophenyl derivatives. None of the compounds tested turned out to have any genotoxic properties.

Bacillus subtilis↗

Biological studies on 2,1-benzisothiazole derivatives. I. Evaluation of antibacterial, antifungal and genotoxic activities of 1-acyl-3-acylimino-2,1-benzisothiazolines.

The in vitro evaluation of antibacterial, antifungal and genotoxic activities of some 1-acyl-3-acylimino-2,1-benzisothiazolines is described. Compounds 55, 58, 60 and 62 exhibited a selective antibacterial activity. Compounds 1, 2, 30, 59 and 63 were active against Botrytis cinerea, compounds 6, 20, 39 and 54 against Pythium irregulare. DNA-damaging activity in the Bacillus subtilis rec-assay was demonstrated for compounds 45, 46, 54, 55, 57 and 61. By the Salmonella-microsome assay, genotoxic activity was confirmed and demonstrated also for compounds 10, 28, 29, 40, 44, 47-53, 56, 58-60, 62 and 63. Relationships between structure and genotoxic activity showed that all compounds containing an aromatic -NO2 group, except compound 27, were active. Among derivatives containing a -CH2Cl group in the acylic chain, only compound 40 showed mutagenic activity.

Animals↗

Cancer and skin sensitivity to intradermal histamine: a preliminary report.

Any meaningful relationship of histamine concentrations, serum IgE concentrations, and the prevalence of cancer is unproven. Several reports indicate that tumor growth is associated with an increased synthesis of histamine. Others demonstrate decreased blood histamine levels and reduced cutaneous response to intradermal histamine in patients with solid malignant tumors. We have evaluated skin sensitivity to intradermal histamine injection, and IgE levels in cancer patients either with or without metastasis. Our data reveal no differences for histamine-induced wheal and flare areas between normal subjects and patients with neoplastic disease (with or without metastasis). In addition serum IgE concentrations were not statistically different. Skin sensitivity to intradermal histamine is not decreased in patients with cancer.

Aged↗

Phase II study of a new alkylating agent (PTT-119) in resistant-relapsed non-Hodgkin's lymphomas.

In a phase II study we evaluated the effect and toxicity of a new alkylating agent, PTT-119, in 26 patients with non-Hodgkin's lymphomas (NHL) resistant to or relapsed after other chemotherapy. PTT was scheduled by escalating the dose from 2.0 to 3.3 mg/kg every 3 weeks. Among 21 evaluable patients with NHL, 12 (57%) showed a good response (CR + PR) to PTT-119. Tolerance was acceptably good; no major side effects related to liver, cardiac, or renal toxicity were recorded. The most commonly recorded side effects were nausea and vomiting, alopecia, and phlebitis; diarrhea and drug-related fever were rarely seen. This report indicates a potential usefulness for PTT-119, a non-cross-resistant alkylating agent, in the treatment of NHL.

Adult↗

Effect of storage on mutagenicity, absorbance and content of furfural in the ribose-lysine maillard system.

The stability with time of browned mixtures characterized by different water activities (aw 0.98, 0.84 and 0.60) and heating temperatures (100, 120, 140 and 160 degrees C) was analysed using the ribose-lysine model system. The results obtained demonstrated the occurrence, during storage, of changes both in the composition of the browned mixtures and in their mutagenic properties, as detected with the Ames test. Only the browned mixtures obtained at 100 degrees C showed a progressive increase in mutagenicity during storage, matched by an increase in ultraviolet and visible light absorbance and of furfural content. In the browning mixtures characterized by a more advanced stage of the Maillard reaction, in which mutagenic activity had initially been found to be undetectable, such activity became evident during storage.

Food Analysis↗

Bone marrow purging for multiple myeloma by avidin-biotin immunoadsorption.

Avidin-biotin immunoadsorption, a technique based on the high affinity between the protein avidin and the vitamin biotin, has been used to remove neoplastic plasma cells from the bone marrow of patients with multiple myeloma. Buffy coat cells obtained from 25 patients were first incubated with monoclonal antibodies (MoAb) capable of recognizing plasma cell-associated antigens (i.e., 8A, 8F6, 62B1, and cocktails of 8A plus 8F6 or 62B1), then with biotinylated goat antimouse immunoglobulin, and passed over a column containing avidin conjugated to Sepharose GMB. Both non-linked and linked cells were analyzed by immunofluorescence and morphological staining. The results showed that over 98% of plasma cells were removed by using 8A or 8F6 alone, while 99.5% +/- 0.4 SD of plasma cell purging was achieved with 2 associated MoAb. In addition, the overall recovery of committed granulocyte-macrophage (CFU-GM),* erythroid (BFU-e), and multilineage (CFU-GEMM) progenitors after column treatment ranged from 39% +/- 15 SD to 50% +/- 6 SD, from 15% +/- 2 SD to 39% +/- 7 SD, and from 16 +/- 4 SD to 64% +/- 10 SD, according to the MoAb employed. On this basis avidin-biotin immunoadsorption appears to be a suitable technique for ex-vivo manipulation of bone marrow infiltrated by neoplastic plasma cells.

Antibodies, Monoclonal↗

Biological studies on 1,2-benzisothiazole derivatives. I. Evaluation of antibacterial, antifungal and DNA-damaging activity.

The in vitro evaluation of antibacterial, antifungal and DNA-damaging properties of some 1,2-benzisothiazole compounds is described. Among all the tested compounds, XXX exhibited the highest antimicrobial activity. A selective antibacterial or antifungal activity was observed for compounds XXI, XXXI and XXXVI. Some of the compounds tested, turned out to have genotoxic properties.

Anti-Bacterial Agents↗

Biological studies on 1,2-benzisothiazole derivatives. II. Evaluation of antibacterial, antifungal and DNA-damaging activities of 3-amino, 3-acylamino, 3-alkylaminoacylamino derivatives.

The in vitro evaluation of antibacterial, antifungal and DNA-damaging properties of some 3-amino, 3-acylamino and 3-alkylaminoacylamino derivatives of 1,2-benzisothiazole is described. Compounds 1-8, 38 and 48 exhibited a selective antifungal activity while the other compounds did not show any significative activity. None of the compounds tested turned out to have any genotoxic properties.

Anti-Bacterial Agents↗

Engraftment in 86 with patients lymphoid malignancy after autologous marrow transplantation.

The kinetics of marrow engraftment was retrospectively analysed in 55 patients with malignant lymphoma (ML) and 31 patients with acute lymphoblastic leukemia (ALL) after marrow-ablative therapy followed by autologous bone marrow transplantation. Thirty-eight percent of patients with ML, most of whom were transplanted in relapse and 13% of patients with ALL, mostly transplanted in remission, showed failed or delayed engraftment. Analysis of the total patient group showed that failure to recover platelet counts was significantly correlated with detection of disease in the marrow early after transplantation (p less than 0.001). Platelet recovery was also correlated with survival (p = 0.0001), disease-free survival (p = 0.0001), and the probability of relapse (p = 0.02). In those patients achieving engraftment, multivariate regression analysis failed to reveal any single in vitro test of marrow nucleated cell or progenitor cell numbers that significantly influenced time to achieve recovery of either granulocyte or platelet counts.

Antineoplastic Combined Chemotherapy Protocols↗

Influence of water activity and reaction temperature of ribose-lysine and glucose-lysine Maillard systems on mutagenicity, absorbance and content of furfurals.

The effect of water activity (aw 0.98, 0.84 and 0.60) and reaction temperature (100, 120, 140 and 160 degrees C) on the mutagenic activity of the Maillard reaction products in heated ribose-lysine and glucose-lysine model systems, was investigated. In the ribose-lysine system, heated at 100 degrees C, the mutagenic activity of the mixture increased as the water activity was lowered. On the contrary, no dependence between mutagenic activity and water activity was observed in the glucose-lysine system. At higher temperatures, in both systems, the presence in the browned mixtures of an antibacterial activity interfering with the bacterial mutagenicity assay was observed. Under all the conditions tested, the ribose-lysine system turned out to be the most reactive by producing higher levels of mutagens. Furthermore, in this system, the antimicrobial interference was more easily detectable. In the model systems used, the browning reaction mixtures were analysed for their absorption spectrum between 200-460 nm, and for the accumulation of furfurals. The results obtained showed that, at temperatures between 120 and 140 degrees C there is a correlation among reaction temperature, absorbance at 420 and around 280 nm, mutagenic activity of the mixture and the level of furfurals. Changes in the levels of furfurals can be related to changes in mutagenicity of the browned mixtures.

Bacteria↗

Critical value of laparotomy with splenectomy in stage III Hodgkin's disease as restaging procedure after chemotherapy.

38 patients with stage III Hodgkin's disease underwent laparotomy with splenectomy as restaging procedure after first line chemotherapy which included MOPP, ABVD, or both. 28 patients were judged to be in clinical complete remission (CR) and 10 were resistant or had relapsed. Among patients in CR, 27 (96%) were confirmed to be in pathological CR; among patients resistant or relapsed, 9 (90%) were confirmed to have disease in the abdomen or retroperitoneum. The therapy for patients in clinical remission before laparotomy consisted of TNI or sTNI in 19 patients, mediastinal radiation in 6 patients and no further therapy in the remaining 3 patients. No significant differences were seen in survival and relapse-free survival between those patients treated by extensive and those treated by local radiotherapy or no further therapy. Instead, among those patients who received extensive radiotherapy 3 developed acute non-lymphoid leukemia (ANLL). The therapy for this group of patients consisted of further chemotherapy in 7 who had concomitant liver involvement and TNI in the remaining 3 who had the disease confined to the spleen and/or lymph nodes. Among these patients, only 3 obtained CR; 2 with radiation and 1 who was resistant to MOPP, with ABVD. This study leads us to re-consider the role of laparotomy in stage III HD which should be used as non-routine procedure only in selected patients without poor prognostic factors who may be cured by radiotherapy alone. In patients resistant to chemotherapy, an early evaluation of disease in the abdomen may be useful for a better salvage treatment.

Adult↗

High-dose chemotherapy with autologous bone marrow transplantation in 50 advanced resistant Hodgkin's disease patients: an Italian study group report.

Fifty patients with recurrent Hodgkin's disease have been treated with high-dose therapy followed by autologous bone marrow transplantation. Forty-one patients had extranodal sites of relapse and 31 patients had constitutional symptoms. Two patients had been treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), lomustine, vinblastine, procarbazine, and prednisone (CcVPP), and radiation; 16 patients with MOPP, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), radiation, and lomustine, etoposide, and prednisone (CEP); 20 patients with alternating MOPP/ABVD, and 12 patients with alternating MOPP/ABVD followed by CEP and radiation. Eighteen patients had progressive disease during alternating MOPP/ABVD protocol alone or during conventional salvage therapy; 32 patients had had a complete remission with first-line therapy but later relapsed, 25 of them having received conventional salvage therapy; 12 achieved no response or progression ("resistant-relapse" patients); and 13 responded partially or completely ("sensitive-relapse" patients). Complete remission occurred in 24 patients (48%) with a median duration of 24 months and 16 patients (32%) achieved partial response with a median duration of 9 months, for an overall response rate of 80%. Ten patients failed to respond and died in progressive disease 1 to 10 months (median, 6 months) after transplantation. Toxicity was significant including infections (20%), liver enzymes and alkaline phosphatase elevations (100%), and carmustine lung toxicity (7%). There were two treatment-related deaths; one patient died of Pseudomonas aeruginosa septicemia and another patient died of cerebral hemorrhage. These results validate the procedure of high-dose therapy followed by autologous bone marrow transplantation in inducing remission in these advanced, highly-treated patients. Clearly, the question of whether high-dose therapy and transplantation will eventually supersede new conventional salvage therapies will be addressed after controlled clinical studies.

Adult↗