Oral valganciclovir treatment in newborns with symptomatic congenital cytomegalovirus infection.

This study was performed to assess oral valganciclovir V-GCV (GCV pro-drug), 15 mg/kg bid for 6 weeks to 13 neonates with symptomatic congenital cytomegalovirus (CMV). We monitored plasma levels of GCV within 30 days of therapy: C(trough), and C(2h) (before and the 2 hours after administration), we performed viral assessment in plasma and urine and tolerability at baseline, and every fortnight. Pharmacokinetics showed GCV stable and effective plasma concentrations: mean C(trough) = 0.51 +/- 0.3 and C(2h) : 3.81 +/- 1.37 microg/ml. No significant variability was seen neither intra-patient nor inter-patients. One newborn discontinued therapy because of thrombocytopenia, another finished with a neutrophils count of 1,000/microl. At the end of therapy 6 out of 12 and 8 out of 12 newborns were negative for CMV in urine and plasma. The 4 newborns positive for CMV DNA showed a 90% reduction of pre-therapy values. Clinically, the 4 patients reporting hepatic disease and the 3 with thrombocytopenia recovered after 6 weeks of therapy. Eight newborns suffered from SNHL; at the 6-month follow-up no patients had worsened, 2 had improved, and no deterioration was reported in 3 newborns with chorioretinitis scarring. The paucity of adverse events, and the effectiveness and stability of drug plasma concentrations are the important findings of our study.

Effects of sex chromosome aneuploidy on male sexual behavior.

Incidence of sex chromosome aneuploidy in men is as high as 1:500. The predominant conditions are an additional Y chromosome (47,XYY) or an additional X chromosome (47,XXY). Behavioral studies using animal models of these conditions are rare. To assess the role of sex chromosome aneuploidy on sexual behavior, we used mice with a spontaneous mutation on the Y chromosome in which the testis-determining gene Sry is deleted (referred to as Y(-)) and insertion of a Sry transgene on an autosome. Dams were aneuploid (XXY(-)) and the sires had an inserted Sry transgene (XYSry). Litters contained six male genotypes, XY, XYY(-), XXSry, XXY(-)Sry, XYSry and XYY(-)Sry. In order to eliminate possible differences in levels of testosterone, all of the subjects were castrated and received testosterone implants prior to tests for male sex behavior. Mice with an additional copy of the Y(-) chromosome (XYY(-)) had shorter latencies to intromit and achieve ejaculations than XY males. In a comparison of the four genotypes bearing the Sry transgene, males with two copies of the X chromosome (XXSry and XXY(-)Sry) had longer latencies to mount and thrust than males with only one copy of the X chromosome (XYSry and XYY(-)Sry) and decreased frequencies of mounts and intromissions as compared with XYSry males. The results implicate novel roles for sex chromosome genes in sexual behaviors.

Pharmacokinetics of nelfinavir in HIV-1-infected pregnant and nonpregnant women.

AIMS: To compare steady-state nelfinavir (NFV) pharmacokinetics in pregnant and nonpregnant HIV-infected women. METHODS: Twenty-five pregnant HIV-infected women were selected from an ongoing observational study evaluating the pharmacokinetics of antiretroviral agents during pregnancy. Twenty of them were in the third and five in the second trimester. Data for the control group of 21 HIV-infected nonpregnant women were taken from a previous multicentre pharmacokinetic trial. All the participating women achieved steady-state plasma concentrations while on a highly active antiretroviral therapy (HAART) regimen including NFV (1250 mg bid) and two nucleoside reverse transcriptase inhibitors (NRTIs). Blood samples for NFV measurement were collected predose (C(trough)) and at 0.5, 1, 2, 3, 4, 5, 6, 8 and 12 h post dose. RESULTS: During the third trimester of pregnancy NFV AUC(0-12 h) median (range) values were 25.76 (12.61-42.74) microg h(-1) ml(-1), and were 32.49 (19.16-63.81) microg h(-1) ml(-1) in the control group [mean difference - 9.30 microg h(-1) ml(-1); 95% confidence interval (CI) -15.76, -2.83; P < 0.05). Median oral clearance (CL/F) was significantly higher in pregnant women than in the control group (48.5 l h(-1), range 29.3-99.1 l h(-1) vs. 38.5 l h(-1), range 19.6-65.2 l h(-1); mean difference 12.6 l h(-1); 95% CI 3.3, 21.9) but the difference disappeared when CL/F was adjusted for body weight. C(trough) was significantly (P < 0.01) lower in pregnant compared with nonpregnant women (median 0.8 microg ml(-1), range 0-2.6 microg ml(-1) vs. 1.5 microg ml(-1), range 0.5-4.9 microg ml(-1); mean difference -1.0 microg ml(-1); 95% CI -1.7, -0.31). The median elimination half-life of NFV observed during pregnancy was 3.7 h (range 1.4-6.6 h), compared with 5.2 (range 3.1-10.1 h) in the control group (mean difference -1.7; 95% CI -2.8, -0.51). CONCLUSIONS: Our results indicate that women in the later stages of pregnancy may be exposed to subtherapeutic concentrations of NFV. Thus, adjustments in drug dosage or frequency of administration may be required.

[Effect of rotting corn straw on the development of bacteria of the Azotobacter group]. / Influencia de la descomposición de la paja de maíz en el desarrollo de bacterias del género Azotobacter

The effects of the addition of ground maize straw, nitrogen compounds, ground lucern and water to soils incubated at 30 degrees C in Erlenmeyer flasks, on Azotobacter chroococcum growth have been studied. The results showed that the highest number of Azotobacter in soils treated with different percentage of ground maize straw without addition of nitrogen compounds and with water at 100% field capacity appeared as soon as the 5th day, reaching a maximun on the 20th day when the following numbers of bacteria were observed: control, 1,5 times 20(6); straw 1% 30 times 10(6), 2%, 33 times 10(6) and 4%, 77 times 10(6) per gram of air dried soil. This enables us to assume that the anaerobic decomposition of straw (cellulose and hemicellulose principally) in nature leads to the indirect utilization of its energy for a high asymbiotic microbiogical soil fixation of atmospheric nitrogen.

[Aplastic crisis in sickle cell anemia induced by parvovírus B19] / Crise aplástica da anemia falciforme condicionada pelo parvovírus B19.

PURPOSE: Transient aplastic crisis is reported in an eight-month old child with sickle cell anemia and acute B19 parvovirus infection. This fact is uncommon in this age. PATIENT AND METHODS: The authors review the literature and describe a clinical case of an eight-month old child with sickle cell anemia presented with profound anemia and reticulocytopenia. His peripheral blood was analyzed for parvovirus B19 using the polymerase chain reaction (PCR), and for anti B19 immunoglobulin Ig M, and Ig G by enzyme-linked immunosorbent assay (ELISA). RESULTS: An eight-month old child with sickle cell anemia was admitted to the hospital with fever and profound anemia (HB = 3.8g/ dl) and reticulocytopenia (2%). A diagnosis of aplastic crisis was established. The results indicate that Ig M and PCR were positive and Ig G negative. The patient needed erytrocyte transfusion, and was discharged on hospital day 4. CONCLUSIONS: The clinical and laboratory features indicate that human parvovirus B19 was the etiologic agent of an aplastic crisis in an eight-month old child. According to the international literature this event is uncommon for this age; in addition, this is the first time it appears in the Brazilian literature.

Phase II study of carboplatin as a single drug for relapsed Wilms' tumor: experience of the Brazilian Wilms' Tumor Study Group.

A total of 15 patients with relapsed Wilms' tumor were treated with carboplatin as a single agent. There were six females and nine males, aged between 2 and 9 years (median:5). The treatment consisted of carboplatin given I.V. as a single agent at a dose of 550 mg/m2 over 1 hour every 3 weeks. There were four (26%) complete responses, four (26%) partial responses, one stable disease, and six with progressive disease. In all patients a total of 56 courses were given and the toxicities found were leukopenia and thrombocytopenia. The overall response rate was encouraging and the toxicity was acceptable and reversible.

Fijacion microbiologica de nitrogeno atmosferico en el suelo, usando paja de maiz como material energetico. / Microbial nitrogen fixation in soils with maize straw as energy source

Se estudio el agregado de la paja de maiz molida (2%), en 30 suelos provenientes de lugares diferentes de la Republica Argentina, incubados en frascos de material plastico, a 30 graus centigrados, con agregado de agua equivalente al 100% de la capacidad de campo. Los tratamientos con paja mostraron un incremento muy elevado del numero de bacterias, aerobias asimbioticas, fijadoras de nitrogeno atmosferico, del genero Azotobacter, en todos los suelos y ademas del genero Beijerinckia en uno de ellos. La fijacion de nitrogeno atmosferico fue elevada con resultados positivos, con el ensayo acetileno/etileno, habiendose obtenido en un suelo un valor equivalente a 57,2 kg de nitrogeno fijado por dia y por hectarea. Los datos obtenidos, la procedencia diferente de las muestras de suelos y los antecedentes existentes, parecen indicar que el proceso microbiologico estudiado en el suelo, incrementado por la paja de maiz, seria un fenomeno universal en todos los suelos que tuvieran las demas condiciones ecologicas requeridas