A histological classification of mucocutaneous leishmaniasis in Brazil and its clinical evaluation

Biopsies of skin and mucosal lesions were made on 60 well documented Brazilian patients with untreated cutaneous or mucocutaneous leishmaniasis, whose response to treatment was subsequently evaluated in 38 cases. The biopsies were examined with a view to classification after correlation with clinical and immunological findings. Although there was no simple or unified spectrum, five histological groups were defined and found to have some clinico-prognostic significance. In two groups the cases were all cutaneous with a relatively good prognosis. In another two groups they were evolving as mucocutaneous with a poor prognosis. The fifth group showed mixed characteristics with a tendency to relapse. There was no strong correlation with serum antibodies or Montenegro skin test, which were usually positive, or with parasite load, which was always low.The tissue response was distinguished from that in oriental sore by the degree of connective tissue involvement in all groups. It was the primary response in two groups, and subsidiary to a mono-nuclear response in the others. It suggested damage due to extra-cellular parasites or immune complexes. It did not correlate with the distinction between cutaneous and mucocutaneous disease. The single, most favourable, prognostic feature in either the cellular or connective tissue component was necrosis with a reactive response.     

Tem-induced gene mutations at enzyme loci in the mouse

Strain DBA/2J male mice were treated with triethylenemelamine (TEM) and subsequently mated to strain C57BL/6J females. Tissues from F₁ progeny produced in these crosses were then examined using starch gel electrophoresis for the presence of presumed induced mutations at a series of 11 specific enzyme loci. In the course of this study, four heritable mutations were identified at the following loci: Es-1, Ldh-1, Pgm-1, and Gpi-1. Of these four, the first two were apparently segregating in parental males and were not TEM-induced. Both of these are viable and fertile in the heterozygous and homozygous condition, and neither confers any readily apparent deleterious effect to the animal. The latter mutations (Pgm-1 and Gpi-1) are presumably induced. Although viable and fertile in the heterozygous state, we have not yet recovered any offspring homozygous for either of these two mutations.     

Some effects of vitamin E deficiency on hepatic xanthine dehydrogenase activity, lead, and alpha-tocopherol concentrations in tissues of lead-dosed mallard ducks.

Three experiments were conducted to determine whether vitamin E deficiency (?E) and/or the oral administration of lead (300 mg/kg body weight) to mallard ducks would affect hepatic xanthine dehydrogenase (XDH) activity and tissue lead deposition. Although there was a significant difference between the +E and ?E plasma α-tocopherol (PαT) and liver α-tocopherol (LαT) concentrations in Experiment 1, XDH activity was unaffected. In Experiment 2, 1-day-old ducklings were fed the experimental diets for 14 days and then given lead (Pb). Forty-eight hours after dosing with Pb the results obtained were similar to those in Experiment 1 except that LαT was distinctly elevated and XDH activity per gram wet weight of liver was significantly depressed in the Pb-treated groups. With Pb treatment the whole blood and liver Pb content was markedly increased. After 96 hr, whole blood, liver, kidney, and spleen Pb concentrations in the +E+Pb group were significantly greater than that in the ?E+Pb group. In Experiment 3, 30-week-old, vitamin E-depleted drakes fed diets similar to those above showed normal XDH activity but marked differences in PαT and LαT were observed. Again the liver Pb content of the +E+Pb group was signficantly greater than of the ?E+Pb group. It appears that XDH activity is not responsive to vitamin E deficiency. Also tissue Pb content, with the exception of drake whole blood lead concentrations, seems to be positively related to vitamin E status.     

Comparison of two regimens for the treatment of elderly patients with acute lymphoblastic leukaemia (ALL)

Acute lymphoblastic leukemia (ALL) represents a rare malignancy in the elderly and few authors have specifically focused on the treatment of ALL in this setting. We recently published the results of a prospective phase II study comprising an induction therapy with vincristine, Daunoxome and dexamethasone (VDXD) given to 15 patients aged 60 years. Here, we update the results after enrolling 17 patients, and we compare these with the results obtained in 17 elderly patients treated according to the GIMEMA ALL 0288 protocol. With the VDXD combination, elderly ALL had a higher CR rate (76.5%) than with the 0288 protocol (41%), and it was likely due to both lower induction mortality (17.5% vs. 35%) and a less resistant disease (6% vs. 24%). Infectious complications were more frequent with the VDXD combination whereas non-hematological side effects were comparable. Despite the similar DFS obtained with the two induction treatments, median EFS (3.9 months with 0288 vs. 12.8 with VDXD; p = 0.0486) and OS (4.5 vs. 21 months; p = 0.0239) were significantly higher with the VDXD regimen. In elderly ALL patients the administration of high-dose daunorubicin as a liposomal compound is feasible and seems able to improve CR rate, EFS and OS without increase in toxicity.     

High-dose radioimmunotherapy combined with fixed, low-dose paclitaxel in metastatic prostate and breast cancer by using a MUC-1 monoclonal antibody, m170, linked to indium-111/yttrium-90 via a cathepsin cleavable linker with cyclosporine to prevent human anti-mouse antibody.

PURPOSE: Although radioimmunotherapy alone is effective in lymphoma, its application to solid tumors will likely require a combined modality approach. In these phase I studies, paclitaxel was combined with radioimmunotherapy in patients with metastatic hormone-refractory prostate cancer or advanced breast cancer. EXPERIMENTAL DESIGN: Patients were imaged with indium-111 (111In)-1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid-peptide-m170. One week later, yttrium-90 (90Y)-m170 was infused (12 mCi/m2 for prostate cancer and 22 mCi/m2 for breast cancer). Initial cohorts received radioimmunotherapy alone. Subsequent cohorts received radioimmunotherapy followed 48 hours later by paclitaxel (75 mg/m2). Cyclosporine was given to prevent development of human anti-mouse antibody. RESULTS: Bone and soft tissue metastases were targeted by 111In-m170 in 15 of the 16 patients imaged. Three prostate cancer patients treated with radioimmunotherapy alone had no grade 3 or 4 toxicity. With radioimmunotherapy and paclitaxel, two of three prostate cancer patients developed transient grade 4 neutropenia. Four breast cancer patients treated with radioimmunotherapy alone had grade 3 or 4 myelosuppression. With radioimmunotherapy and paclitaxel, both breast cancer patients developed grade 4 neutropenia. Three breast cancer patients required infusion of previously harvested peripheral blood stem cells because of neutropenic fever or bleeding. One patient in this trial developed human anti-mouse antibody in contrast to 12 of 17 patients in a prior trial using m170-radioimmunotherapy without cyclosporine. CONCLUSIONS: 111In/90Y-m170 targets prostate and breast cancer and can be combined with paclitaxel with toxicity limited to marrow suppression at the dose levels above. The maximum tolerated dose of radioimmunotherapy and fixed-dose paclitaxel with peripheral blood stem cell support has not been reached. Cyclosporine is effective in preventing human anti-mouse antibody, suggesting the feasibility of multidose, "fractionated" therapy that could enhance clinical response.