Brain alterations in GABA, glutamate and glutamine markers after chronic atrazine exposure in the male albino rat.

Atrazine (ATR; 2-chloro-4-ethylamino-6-isopropylamino-s-triazine) is an herbicide widely used to kill annual grasses and broadleaf weeds in crops such as corn, sorghum, and sugarcane. Studies in rodents have shown that chronic ATR exposure is associated with alterations in the nigrostriatal dopaminergic pathway such as hyperactivity, decreased striatal dopamine levels, and diminished numbers of tyrosine hydroxylase positive cells in substantia nigra pars compacta. However, the effects of ATR on neurotransmitters such as GABA and glutamate have been scarcely studied. To evaluate the impact of ATR on motor and anxiety tasks, tissue levels of GABA, glutamate, glutamine, and extracellular and potassium-evoked release of glutamate in the striatum, we daily exposed Sprague-Dawley male rats to 1 or 10 mg ATR/kg of body weight for 12-14 months. As previously reported, chronic ATR exposure causes hyperactivity in the group exposed to 10 mg ATR/kg and increased anxiety in both groups exposed to ATR. GABA, glutamate, and glutamine levels were differentially altered in brain regions related to nigrostriatal and mesolimbic systems, the amygdala, and the prefrontal cortex. The groups exposed to 10 mg ATR/kg showed increased extracellular levels and release of glutamate in the striatum. These neurochemical alterations could underlie the behavioral changes observed in rats. These results indicate that chronic exposure to the herbicide ATR disrupts the neurochemistry of several brain structures and could be a risk factor for the development of neurodegenerative diseases.

An experimental subunit vaccine based on Bluetongue virus 4 VP2 protein fused to an antigen-presenting cells single chain antibody elicits cellular and humoral immune responses in cattle, guinea pigs and IFNAR(-/-) mice.

Bluetongue virus (BTV), the causative agent of bluetongue disease (BT) in domestic and wild ruminants, is worldwide distributed. A total of 27 serotypes have been described so far, and several outbreaks have been reported. Vaccination is critical for controlling the spread of BTV. In the last years, subunit vaccines, viral vector vaccines and reverse genetic-based vaccines have emerged as new alternatives to conventional ones. In this study, we developed an experimental subunit vaccine against BTV4, with the benefit of targeting the recombinant protein to antigen-presenting cells. The VP2 protein from an Argentine BTV4 isolate was expressed alone or fused to the antigen presenting cell homing (APCH) molecule, in the baculovirus insect cell expression system. The immunogenicity of both proteins was evaluated in guinea pigs and cattle. Titers of specific neutralizing antibodies in guinea pigs and cattle immunized with VP2 or APCH-VP2 were high and similar to those induced by a conventional inactivated vaccine. The immunogenicity of recombinant proteins was further studied in the IFNAR(-/-) mouse model where the fusion of VP2 to APCH enhanced the cellular immune response and the neutralizing activity induced by VP2.

Non-cryopreserved unmanipulated hematopoietic peripheral blood stem cell autotransplant program: long-term results.

BACKGROUND: Methods to simplify bone marrow transplantation procedures are needed mainly in developing countries. METHODS: Between May 1993 and February 1999 in a private-practice setting, we performed 29 autotransplants in 28 patients using non-cryopreserved and unmanipulated peripheral blood stem cells mobilized from the bone marrow to the peripheral blood by means of hematopoietic growth factors. The autografting procedure was performed entirely on an outpatient basis in 19 cases (65%). The median age of the patients was 30 years, with a range of 9-67. There were 15 patients with acute leukemia (9 with acute myelogenous leukemia), 3 with chronic myelogenous leukemia, 2 with multiple myeloma, 3 with Hodgkin's disease, 2 with non-Hodgkin's lymphoma, and 4 with metastatic breast carcinoma. RESULTS: The median time to achieve > 0.5 x 10(9)/L granulocytes was 14 days (range 7-42), whereas the median time to achieve > 20 x 10(9)/L platelets was 20 days (range 5-49). The 64-month post-transplant survival was 38%, whereas the median post-transplant survival was 18 months. The transplant-related mortality was 3.4%. The approximate cost of this simplified procedure was 10.8% for in-hospital procedures and for outpatient autografts, substantially lower than figures reported from the U.S. for autotransplants. CONCLUSIONS: This simplified method for autografting patients, avoiding in-hospital stays, purging procedures and cryopreservation of the cells is feasible and results in a substantial decrease of the cost of autologous hematopoietic stem cell transplantation methods.

Splenectomy complications in hematological diseases.

The postoperative complications observed in a group of 27 patients with hematological diseases that underwent splenectomy are reported: 21 patients had a non-malignant hematological condition, whereas the rest had a hematological malignancy. Seven complications presented in 6 patients (two wound infections, two severe post-operative hemorrhages, one incisional hernia, one sepsis by capsulated bacteria and one fatal hemophagocytic syndrome). The overall complication rate was 27%, whereas the fatal complication rate was 3%. The complication rate in patients with malignant diseases was 83%, whereas that in benign conditions was 9%. The size of the spleen was related with the complication rate (median weight of patients with complications was 990 g versus 132 g in those without complications; p < 0.01). The two patients that underwent splenectomy before age six months had complications, in one case related to parental negligence. In splenectomies performed for hematological disease the benefits must be balanced carefully against the risks.

Non-cryopreserved peripheral blood stem cells autotransplants for hematological malignancies can be performed entirely on an outpatient basis.

We have prospectively performed peripheral blood stem cell autotransplants in six patients with hematological malignancies on an entirely outpatient basis. Patients were conditioned with high-dose melphalan and received a median of 4.2 x 10(8)/kg non-cryopreserved, non-purged mononuclear cells, containing a median of 3.9 x 10(6)/kg CD34 + cells. The median time to achieve > 500 granulocytes/microl was 21 days, with a range of 16 to 40, whereas the median time to achieve > 20,000 platelets/microl was 38 days, with a range of 21 to 48. Only three patients were transfused with platelets whereas packed red blood cells were transfused in two. All patients survived 60 days after the autograft and three are alive at 450, 690, and 1,950 days after the autotransplant. One patient was given an allogeneic bone marrow transplant when relapsing after the autotransplant. One patient had to be admitted to the hospital on day +10 because of fever. A median of 6,500.00 USD per patient was calculated as the total cost of each outpatient autotransplant. Since outpatient autologous transplants with non-frozen PBSC are feasible, restrictions to PBSC autotransplant programs may be overcome and costs may be diminished.

Filgrastim-mobilized peripheral-blood stem cells can be stored at 4 degrees and used in autografts to rescue high-dose chemotherapy.

We studied 21 filgrastim (G-CSF)-mobilized peripheral blood stem cells (PBSC) apheresis products obtained from seven patients, and stored at 4 degrees C for periods of up to 96 hr prior to their reinfusion, to rescue high-dose chemotherapy. The apheresis products contained a median of 106 x 10(8)/L mononuclear cells (MNC), 14.6% of them displaying the CD34 antigen; the viability was over 90% in all samples studied at 24, 48, and 72 hr after harvesting. These PBSC were successfully used to rescue high-dose chemotherapy; patients received a median of 4.8 x 10(8)/Kg MNC; the median time to achieve > 500 granulocytes was 14 days (range 11-26) and the median time to achieve > 20,000 platelets was 20 days (range 11-40). Since autologous transplants with nonfrozen PBSC are feasible and less costly than those using frozen PBSC, restrictions to PBSC autotransplant programs may be overcome and costs may be diminished.

Outpatient supportive therapy after induction to remission therapy in adult acute myelogenous leukaemia (AML) is feasible: a multicentre study.

Twenty-four adult patients with AML were treated with standard "7 + 3" chemotherapy. After administering the myeloablative drugs in the hospital, patients were instructed to continue their supportive treatment on an outpatient basis; they received ciprofloxacin, cotrimoxasole and itraconazole vo until the absolute granulocyte count rose above 1 x 10(9)/l. Platelet concentrates were given every other day until the platelet count rose above 20 x 10(9)/l. Complete remission (CR) was obtained in 87%. Fever developed in 29% and 2 cases were complicated by indwelling-catheter-related Pseudomona aeruginosa septicaemia, 1 Entamoeba hystolytica enteritis and 1 Pneumocystis carinii pneumonia; these patients were hospitalized to treat these infections specifically. In no case was the infection fatal. The median disease free-survival (DFS) was 17 months, 12-month DFS was 66%, and 30-month DFS was 17%. Our calculations have shown that 1700 USD/patient were saved by avoiding prolonged hospitalization; this may provide not only economical, but also psychological advantages to patients.

[Autotransfusion and pregnancy]. / Autotransfusión y embarazo.

PURPOSE: To analyse the results of a pre-deposit autologous transfusion programme in pregnant women on their third period of pregnancy. MATERIAL AND METHODS: Fifty donor/pregnant women were included in the study. They were in the third trimester of their pregnancy and had risk of requiring transfusion during or after surgery. Haemoglobin above 11 g/dL and haematocrit above 34% were required in each case. Phlebotomy was performed at one-week intervals, iron and folate being supplied. Constants such as foetal heart frequency were evaluated, the programme being interrupted in case of foetal bradycardia. Apart from weight, Apgar and Silverman scores were applied to each newborn. RESULTS: Cephalopelvic disproportion was the commonest obstetric indication, 26 cases (52%). For autologous blood transfusion, rare blood groups, 12 cases (24%), followed by intra- or post-operative bleeding risk, 10 cases (20%) and being Jehovah's Witnesses, 9 cases (18%), were the major indications. Ninety-four blood units were drawn, 34 of them being used. The remaining 60 units were used for homologous transfusion. No complications developed during phlebotomy and the neonatal determinations showed no significant anomalies. CONCLUSIONS: (1) Autologous blood transfusion with pre-deposit in the third trimester of pregnancy is a safe and effective way of collecting blood. (2) Its indication is not reduced to rare blood groups. (3) The procedure seems to be safe for both the mother and the newborn.

[Malnutrition is an adverse prognostic factor in the response to treatment and survival of patients with acute lymphoblastic leukemia at the usual risk]. / La desnutrición es un factor pronóstico adverso en la respuesta al tratamiento y supervivencia de pacientes con leucemia aguda linfoblástica de riesgo habitual.

A group of 43 pediatric patients with standard risk acute lymphoblastic leukemia (ALL) was studied prospectively and treated with a protocol that included adriamycin, vincristine and prednisone (HOP) to induce remission; cranial irradiation and intrathecal methotrexate (MTX) as CNS prophylaxis and mercaptopurine and MTX together with pulses of HOP every three months to maintain remission. Complete remission (CR) was achieved in 95.3% of the group; 5-year survival was 67%. The following variables were analyzed in the outcome to treatment: Age, sex, WBC at diagnosis, FAB morphology, CALLA/CD10 reactivity of the blast cells, lymph node, liver or spleen enlargement, site of treatment (private practice versus city hospital) and malnutrition. None of these variables had a significant impact in survival, but malnutrition. Under-nourished children (UNC) n = 16, had a significant worse outcome than well-nourished children (WNC) n = 27. Although CR was achieved in 98% of WNC versus 94% of UNC, five-year survival was 83% for WNC and 26% for UNC (p less than .001); relapses were observed in 18% of WNC and 75% of UNC (p less than .0005). Relapses presented more frequently in the bone marrow in UNC than in WNC (56% versus 7% p less than .0001). The doses of maintenance chemotherapy had to be reduced in 68% of UNC and 10% of WNC (p less than .005). The poor outcome to treatment observed in UNC was due to systemic relapses, apparently related to a poor tolerance to maintenance chemotherapy. Malnutrition might be included as an adverse prognostic factor in the outcome to treatment of children with ALL, in developing countries.

[Preliminary report on the effect of low doses of azidothymidine (AZT) in the treatment of patients with stage III infection by human immunodeficiency virus (HIV)]. / Informe preliminar del efecto de las dosis bajas de azidotimidina (AZT) en el tratamiento de pacientes con estadio III de infección por el virus de la inmunodeficiencia humana (VIH).

Ten patients with CDC stage III of infection by HIV were treated with AZT at doses of 300 mg/day (100 mg tid). There were 5 males and 5 females, the median age being 40.5 yr' (range 26-46). Seventy percent of them had transfusion-associated HIV infection and the rest had been infected by the sexual route. A positive clinical response was observed in 100% of the group after 16-24 weeks of treatment: the Karnofsky performance status increased from 64% to 94% (p less than 0.01), the white blood cell count raised from 3.7 to 6.0 K/microL (p less than 0.01), the number of helper lymphocytes (CD4+) also raised significantly from 248.2 to 470.7/uL (p less than .01). Only two patients required red blood cells transfusions. The life expectancy at 82 weeks was 90%. Toxicity was both moderate and transitory. It is concluded that low doses of AZT (300 mg/day) produce similar clinical results as doses of 1200-1500 mg/day. A larger study is needed to support our preliminary findings.

Congenital Acute Megakaryoblastic Leukaemia in Down's Syndrome.

The case of a newborn with Down's syndrome and congenital leukaemia is reported. The malignant white blood cells displayed the CD41 antigen (glycoprotein Ilb/IIIa) identified by monoclonal antibodies HP1-ld and FMC24 and the CD9/p24 antigen identified by monoclonal antibody FMC27. The number of cells in S-phase was 14%, as assessed by the incorporation of 5-bromo 2-deoxyuridine. No other chromosomal abnormalities were identified in addition to 47 XY + 21. The patient died 15 days after the diagnosis, due to Pneumocystis Carinii pneumonia. Post-mortem examination showed heavy leukaemic infiltration and cardiac abnormalities including inter-atrial septal defect and a patent Ductus arteriosus. This patient appears to be the first identified case of congenital leukaemia with megakaryocytic differentiation, although previous instances of transient abnormal myelopoiesis with megakaryocytic differentiation have been recorded in Down's syndrome.

[Paid blood donors: a new risk group for the development of AIDS in Mexico]. / Donadores sanguíneos remunerados: un nuevo grupo de riesgo para desarrollar SIDA en México.

We analyzed the clinical and epidemiological characteristics of seven patients with AIDS who were infected through contaminated needles or blood letting equipment; no other risk factor was identified in these patients. In the Dirección de Epidemiología de los Servicios Coordinados de la Salud in the state of Puebla, 37 cases of AIDS were registered up to June 15, 1988. Nineteen percent of these were paid donors between the ages of 26 and 45. There were five males and two females. All of them had weight loss, fever, chronic diarrhea and adenomegaly. Six had respiratory complaints, four candidiasis and two pulmonary tuberculosis. In the state of Puebla, there are 517 paid donors registered as carriers of Human Immune Deficiency Virus (HIV). We do not know the number of blood donations and therefore the number of receptors. In this state, 52 percent of AIDS cases are post-transfusional and we fear an increase. We propose that all paid blood donors should be considered as a high risk group.

["Occupational" infection caused by the human immunodeficiency virus in 6 members of a single family]. / Infección "ocupacional" por el virus de inmunodeficiencia humana en seis miembros de una misma familia.

The risk groups for AIDS have been defined and include homosexuals, bisexuals, polytransfused patients, drug addicts, sexual partners of any of the above groups and sons of infected fathers. We have previously proposed that paid donors should be considered also as high risk individuals. We report here a family in which six of its eight members had HIV infection without other risk factor than being paid blood donors.

[High prevalence of acquired immunodeficiency syndrome (AIDS) associated with transfusion in Puebla, Mexico]. / Prevalencia alta de síndrome de inmunodeficiencia adquirida (SIDA) asociado a transfusion en Puebla, México.

The salient clinical and epidemiological features of the first cases of AIDS diagnosed in the city of Puebla, Mexico, are reviewed. Puebla has 2 million inhabitants and 37 cases of AIDS have been diagnosed since 1984. Thirty-two percent of patients acquired AIDS by blood transfusion, 20% were paid blood donors and 48% acquired the HIV infection by the sexual route, thus making a 52% prevalence of transfusion-related HIV infection. These data are substantially different from those reported in other countries and in other cities within Mexico, where the prevalence of transfusion-associated HIV infection is about 11.5%. The high prevalence of transfusion-related AIDS seems to be due to existence of "blood centers" where paid donors are bled using non-disposable material, and they are poorly selected. HIV infection is thus transmitted to paid-blood donors which in turn become transmitters of the disease. The new regulations on blood donation adopted in Mexico abolish paid blood-donation and the selection of blood donors is more stringent. This should result in reducing the serious problem of transfusion-associated HIV infection in the city of Puebla, Mexico.

[High doses of cytosine arabinoside in the treatment of patients with acute relapsing or refractory leukemia]. / Dosis altas de arabinósido de citosina en el tratamiento de pacientes con leucemia aguda refractaria o en recaída.

Ten patients either in relapse (n = 7) or refractory (n = 3) acute leukemia were treated with high-dose Ara-C (3000 mg/m2) every 12 hours to a total of eight 2 doses (24,000 mg/m2). Myeloblastic (n = 5), lymphoblastic (n = 4) and hybrid (n = 1) acute leukemias were included. In the total group, complete remission was achieved in 6 of 10 cases (60%); the remission rate was higher in the relapsed than in the refractory acute leukemia group (71 versus 33%;) the duration of the complete remission ranged between 1 and 13 months, with a median of 2 months; the remission duration was also higher in the relapsed than in the refractory acute leukemia group (4 versus 1 month). Refractoriness to the high-doses of Ara-C was observed in two cases, and fatal iatrogenic myelosuppression was produced in two patients. The rate of complete remission was 80% in myelogenous leukemia and 50% in lymphoblastic leukemia. It is concluded that high-dose Ara-C is another therapeutic choice in the treatment of relapsed and perhaps refractory acute leukemia.