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Isolates of Marek's disease virus (MDV) from vaccinated flocks in Argentina were characterized as very virulent (vv) and very virulent plus (vv+) strains. Experimental infection with these viruses caused a high incidence of Marek's disease in both resistant N-2a line and susceptible P-2a line birds. Vaccine viruses from each of the three Marek's disease viral serotypes were evaluated alone and in various combinations for protection against challenge with a vvMDV called NULP-1. Vaccination of P-2a birds with HVT did not protect satisfactorily against any of the vv and vv+MDV strains isolated. However, CVI988/Rispens vaccine alone or combined with serotype 2 and/or serotype 3 vaccine strains enhanced protection significantly against NULP-1. Serotype 2 plus serotype 3 vaccines also provided significant protection when challenged with this strain. This is one the first reports of the occurrence of vvMDV and vv+MDV in Argentina and Latin America. It is also a preliminary evaluation of the synergistic protective effect of different vaccine viruses with local MDV strains. However, further studies are needed to evaluate the real role of these and other Marek's disease isolates in 'vaccination failures' and the influence of serotype and virus strain on synergism between Marek's disease vaccine viruses.

The electron spin resonance (ESR) spectra of free radicals obtained by electrolytic or microsomal reduction of several potential antiprotozoal 1,2,5-oxadiazoles were characterized and analyzed. Ab initio molecular orbital calculations were performed to obtain the optimized geometries and the theoretical hyperfine constant was carried out using ZINDO semiempirical methodology. Density functional theory was used to rationalize the reduction potentials of these compounds.

Forty-three consecutive patients with de novo and untreated non M3 AML aged 60 or less entered the study. The mean age of patients was 50 (range 15-60). The induction regimen (FLAG-Ida) included fludarabine (30 mg/sqm), Ara-C (2 g/sqm) on days 1-5, and idarubicin (10 mg/sqm) on days 1, 3, 5. G-CSF (300 mcg/day) was administered s.c. 12 hours before starting fludarabine and was continued for five days. HDT with stem cell rescue was planned for all patients in first CR after one course of high dose Ara-C (HDAC) consolidation and in good clinical conditions. Forty-two (98%) patients were evaluable for response. One patient died during induction (2%). CR was achieved in 35 patients (82%). Twenty-three patients, 66% of those achieving CR, underwent autologous (N = 17) or allogeneic (N = 6) transplantation. With a median follow up of 24 months, the average median duration of CR is 17 months (range 3-66) and the median survival is 20 months (range 1-83). Overall the 5 year projected disease free survival (DFS) and overall survival (OS) were 37% and 43%, respectively. Among patients who underwent stem cell transplantation DFS and OS were 53% and 69%, respectively. The median time to PMN recovery (> 0.5 x 10(9)/l) was 17 days (range 10-28) and 50 x 10(9)/l platelets were reached at a median of 17 days (12-38). In conclusion FLAG-Ida regimen is effective, low toxic and improves feasibility of stem cell transplant.

The study of antibody avidity changes during infection has improved the understanding of the pathologic processes involved in several infectious diseases. In some infections, like toxoplasmosis, this information is being used for diagnostic purposes. Results of the evolution of antibody avidity for different specific antigens in Trypanosome cruzi-infected rats are presented. A Western blotting technique, combined with avidity analysis to identify antigens that elicit high-avidity antibodies, is suggested. In this system, antibodies showed high avidity values only during the chronic phase of infection and only in relation to antibodies against 21-, 33-, 41-, 42-, 56-, 58-, 66-, and 72-kDa antigens. Finally, a 97-kDa T. cruzi antigen, which was recognized by high-avidity antibodies and occurred in noninfected rats, was identified. These results allow us to evaluate the different antigens in chagasic infection. Our results show that with the correct choice of antigen it is possible to detect differences in maturation of antibodies and to discriminate, in an experimental model, between recent (acute) and chronic infections.

Several new 1,2,5-oxadiazole N-oxide derivatives were synthesized to be tested both as potential selective hypoxic cell cytotoxins and as DNA-binding agents. The compounds prepared included bis(1,2,5-oxadiazole N-oxide) derivatives and oxadiazole rings linked to naphthyl residues. The compounds were tested for their cytotoxicity in oxia and hypoxia and they proved to be non-selective and less active than the parent compounds 3-formyl-4-phenyl-1,2,5-oxadiazole N2-oxide (3) and 3-chloromethyl-4-phenyl-1,2,5-oxadiazole N2-oxide (4). The DNA-affinity assays showed that the compounds tested have poor affinity for this biomolecule.

The syntheses of a new series of derivatives of 1,2,5-oxadiazole N-oxide, benzo[1,2-c]1,2,5-oxadiazole N-oxide, and quinoxaline di-N-oxide are described. In vitro antitrypanosomal activity of these compounds was tested against epimastigote forms of Trypanosoma cruzi. For the most effective drugs, derivatives IIIe and IIIf, the 50% inhibitory dose (ID50) was determined as well as their cytotoxicity against mammalian fibroblasts. Electrochemical studies and ESR spectroscopy show that the highest activities observed are associated with the facile monoelectronation of the N-oxide moiety. Lipophilic-hydrophilic balance of the compounds could also play an important role in their effectiveness as antichagasic drugs.

The new purine-analogue 2-chlorodeoxyadenosine (2-CdA) has proved to induce an high CR rate and a long lasting disease free survival. In this study we compare the efficacy and toxicity of 2-CdA employed in two different schedules (A and B). Forty-one patients have been enrolled from 1994: 22 p. (group A) were treated with a single cycle of 2-CdA given as two hour i.v. infusion on 5 consecutive days (0.15 mg/kg/die); while 19 p. (group B) with continuous i.v. infusion for 7 consecutive days (0.10 mg/kg/die). Response criteria were those proposed by NCI. The Hairy Cell Index (HCI) was calculated using DBA44 MoAb. At three months, the responses in group A (19/22) were: 5 CR (26.3%), 6 GPR (31.5%), 5 PR and 3 NR.; in group B (17/19): 6 CR (35.3%), 3 GPR (17.6%), 4 PR and 4 NR. Overall response at six months was respectively 84.2% and 76.5%. At six months the responses were: in group A (18/22): 9 CR (50%), 4 GPR (22.2%), 3 PR, 2 NR; in group B (16/19): 4 CR (25%), 6 GPR (37.5%), 3 PR, 3 NR. Overall response at 6 months was respectively 88.8% (group A) and 81.2% (group B). The 5 day intermittent schedule appears efficient, well tolerated and suitable for out-patient treatment. DBA44 MoAb appears useful to better define the HCI and to distinguish CR from GPR.

Two direct methods for the diagnosis of trichinellosis were compared: trichinoscopy and artificial digestion. Muscles from 17 wistar rats, orally infected with 500 Trichinella spiralis encysted larvae were examined. From each of the following muscles: diaphragm, tongue, masseters, intercostals, triceps brachialis and cuadriceps femoralis, 648,440 larvae from 1 g samples were recovered. The linear correlation between trichinoscopy and artificial digestion was very high and significant (r = 0.94, p < 0.0001), showing that both methods for the detection of muscular larvae did not differ significantly. In both methods, significant differences were found in the distribution of larvae per gramme of muscle.

The aim of this study was to determine whether repeated ingestion of mycotoxin T-2 (T2) or aflatoxin B1 (AFL) at low doses could contribute to the activation of toxoplasmosis in experimentally infected mice. Mice were divided into two groups: Control (C) and Infected (I). The cyst-forming Beverley strain of Toxoplasma gondii was used to produce the infection one month before treatment with mycotoxins. Mycotoxins were given intragastrically for a 50-day period. The average weight gain was reduced in the groups treated with mycotoxins. Mice developed specific IgG to T. gondii. Histopathological studies showed severe encephalitis in all groups infected. The number of unruptured and ruptured cysts was established and the severity of the lesions was evaluated, the groups treated with mycotoxins being the most severely affected. Immunohistochemical studies of the brain showed free antigen in tissues surrounding ruptured cysts. It is suggested that low and repeated doses of mycotoxins, necessary to produce a subclinical intoxication, precipitate Toxoplasma cyst rupture and consequently the activation of chronic toxoplasmosis.

Forty consecutive adult patients under the age of 50 with acute non-lymphoblastic leukemia (ANLL) in first complete remission, underwent autologous bone marrow transplantation (ABMT) between March 1984 and April 1990. The conditioning regimen employed included cyclophosphamide and total body irradiation, followed by the administration of unpurged ABMT. The median time from diagnosis to transplant was 7 months (3-15 months), and the median time from complete remission to ABMT was 4 months (range 3-9 months). Twenty-two (51%) patients remain in complete remission 6-81 months (median 24 months) after ABMT. The causes of death were, recurrent leukemia (11 patients), parenchymal toxicities such as acute respiratory distress syndrome and veno-occlusive disease (3 patients), hemorrhage (2 patients) and infection (2 patients). Eleven patients relapsed after 3-12 months (median 5 months). This study has produced survival data comparable to those of other institutions employing TBI for either allo or autotransplants.

The effects of aflatoxin B1 on the development of the immune response to oil-adjuvanted Bordetella bronchiseptica vaccine and on acquired resistance to bacterial challenge were studied in rabbits. The doses of aflatoxin used were insufficient to produce clinical intoxication. Rabbits were randomly assigned to three groups, each having six animals: control (T), vaccinated (V), and vaccinated plus aflatoxin (VA) at 0.05 mg/kg daily per os. Groups V and VA were vaccinated twice, and the three groups were subsequently challenged with virulent B. bronchiseptica. The average weight gain at weekly intervals was significantly reduced in group VA, and no statistically significant differences were found in the titers of agglutinating antibodies between groups V and VA. There were significant differences between groups V and VA in the extent and severity of the pneumonic process, group VA being most affected. Results indicated that agglutinating antibody titers were not related to the level of protection in the latter group. Other mechanisms, such as alveolar macrophage activity and cell-mediated immunity, were implicated in the impairment of the acquired resistance in rabbits subclinically intoxicated with aflatoxin.

Sixty-seven unselected adult patients with untreated acute non lymphotblastic leukemia (ANLL) ranging in age from 15 to 80 years received a new induction regimen consisting of Idarubicin, Etoposide and Cytarabine. Patients who entered complete remission (CR) were then allocated to 4 courses of post remission intensification. After this, patients under 50 years of age with a compatible donor were given allogeneic bone marrow transplantation (BMT) or autologous BMT (ABMT) in those without an HLA-compatible donor; the remainder, older than 50, did not receive further therapy. Fifty-six of 67 patients (83.5%) achieved CR (02.5% in young and 70.3% in old patients) and 40 (71 %) after the first course. Seven patients (of whom, 6 were > 50 years) died in aplasia during the induction phase and four additional patients (all elderly) died during post-remission intensification without recurrent disease. Subsequently, the younger patients received transplants (BMT: 4 pts; ABMT: 10 pts). Twelve: of the 52 (23%) who survived post remission intensification (BMT: 1; ABMT: 4; others: 7) are disease free survivors 9-67 months (median, 32 months) after achieving CR. In conclusion, this intensive chemotherapy regimen is highly effective both in young and odder patients but the post-remission intensification may be too aggressive for elderly patients.

The author examines some aspects of the history of psychiatry in order to show that psychiatry follows the path traced by the ideology of medicine. The psychiatric hospital was, and continues to be, the place in which psychic suffering is transformed into an "organic" disease; and where the symptom-alteration of behaviour, is still referred to as a "lesion", even though, after one and a half century of research, this idea has not yet been proved. Today, as yesterday, the term "endogenous" is correctly used to indicate major mental diseases; this is a term indicating that we know nothing about the origin of these diseases. However, psychiatry behaves as though it knew. Psychiatrists formulate diagnoses, implement organic therapies, prescribe drugs and reconfirm a nosology which should be seriously reconsidered. In other words, psychiatry continues to be the field of ideological transformation, of the social into the biological, as well as the field of biological justification for mechanisms of social exclusion.

Forty-two patients with severe aplastic anemia (SAA) were treated with immunosuppressive therapy (IS) consisting of one or more courses of the following regimens: a) high dose bolus 6 methylprednisolone (BMPr); b) horse antilymphocytic globulin (HALG); c) rabbit ALG (RALG); d) ALG followed by the infusion of haploidentical marrow (ALG +/- BM); e) BMPr in combination with HALG; f) ALG in combination with androgens. All patients received one initial course of IS: 16 (38%) showed hematologic reconstitution and required no further transfusions, of 26 refractory patients 4 died, and 22 received a second course of IS 60 days after the first course. Of these 22, 6 (27%) responded, and of the 16 refractory patients, 9 died, and 7 received a third course of IS 60 days after the second course. Two of these responded (28%), 3 died and 2 are alive but pancytopenic. The overall response rate is 24/42 patients (57%): all of these patients are transfusion independent 6-60 months post-treatment, and 17 are off maintenance therapy with low dose steroids. The actuarial 5 year survival is currently 60%; 13/26 surviving patients have been followed for more than 3 years. The present study confirms that over 50% of patients with SAA can recover from their aplasia following IS treatment, and this is of relevance for patients who can not be offered a bone marrow transplant.

Twenty-five adults with previously treated acute leukemia were treated with 4-demethoxydaunorubicin (Idarubicin) with a daily dose of 8 mg/m2 for 3 days intravenously. Complete remission was achieved in 3 of 18 patients with acute nonlymphoblastic leukemia (ANLL) and 2 of 6 with lymphoblastic leukemia. Complete remissions were observed in two of eight ANLL patients refractory to cytarabine, anthracycline, and m-Amsa (amsacrine), indicating a lack of cross-resistance between these drugs and Idarubicin. The median duration of remission was 8 weeks. The main major toxicity of Idarubicin therapy, severe myelosuppression, cannot be considered a toxic effect because it was desired in this case list. Our preliminary results indicate that Idarubicin has significant activity against refractory adult acute leukemia.

Massive pulmonary infiltration by leukemic cells resulting in respiratory symptoms is a rare complication of acute leukemia. We report the findings in a patient with acute myelomonocytic leukemia presenting with acute onset of fever, dyspnea, and nonproductive cough, in whom the diagnosis of pulmonary invasion by leukemic cells was made by cytochemical analysis of bronchoalveolar cells recovered by lavage.

Thirty-one unselected patients with untreated acute non lymphoblastic leukemia (ANLL) ranging in age from 15 to 76 years received two courses of a new high-dose induction regimen consisting of idarubicin, etoposide and cytarabine. Patients who entered complete remission (CR) were then allocated to post-remission intensification (PRI). Patients under 40 years of age with a HLA-compatible donor were given bone marrow transplantation (BMT); those without an HLA identical donor received either autologous BMT (ABMT) or no subsequent therapy. Twenty-five out of 31 patients (80.6%) achieved CR (93.3% in young and 68.7% in old patients) and 14 (56%) after the first cycle. Six patients (five out six greater than 40 years) died of cerebral hemorrhage and/or infection during the induction phase and four additional patients (three elderly) died on the PRI for the same cause without recurrent disease. Eleven out 25 patients are disease-free survivors 2-34 months (median 10 months) after achievement of CR. In conclusion, this intensive chemotherapy regimen is effective both in young and older patients but the post-remission intensification is too aggressive in elderly patients.

In vitro colony formation (CFUC) was studied in 8 patients with severe aplastic anemia (SAA) in complete hematologic remission following high dose pulse methylprednisolone (P/6-MPr) and/or antilymphocyte globulin (ALG). All patients except one were off maintenance treatment at the time of study, and follow-up ranged from 271 to 630 days. All patients showed marked reduction of colonies (2 +/- 3/2.5 x 10(5) cells; our normal 61 +/- 14) and clusters (77 +/- 45; our normal 179 +/- 83), which persisted for as long as 600 days after initial therapy. Incubation of patients' marrow with ALG did not enhance significantly colony formation. Co-culture of bone marrow from 6 patients with SAA in remission and normal marrow produced a marked inhibition of the expected colonies (84 +/- 16%) and clusters (29 +/- 23%). Incubation of patients' marrow with ALG prior to the co-culture experiments did not prevent suppression of colonies and clusters. Co-culture of patients' peripheral blood lymphocytes with normal marrow had no effect on colony formation. Therefore remission marrow from patients with SAA exhibits severely impaired in vitro growth (CFUC) and marked myelosuppressive activity against normal marrow cells. Incubation of patients' marrow with ALG has no significant effect on either assay.