Resolution of homonymous visual field loss documented with functional magnetic resonance and diffusion tensor imaging.

A 68-year-old man developed right homonymous hemianopic paracentral scotomas from acute infarction of the left extrastriate area. He was studied over the ensuing 12 months with visual fields, conventional MRI, functional MRI (fMRI), and diffusion tensor imaging (DTI). As the visual field defect became smaller, fMRI demonstrated progressively larger areas of cortical activation. DTI initially showed that the lesioned posterior optic radiations were completely interrupted. This interruption lessened in time and had disappeared by one year after onset. fMRI and DTI are innovative measures to follow functional and structural recovery in the central nervous system. This is the first reported application of these imaging techniques to acute cerebral visual field disorders.     

外侧裂区脑挫裂伤31例临床分析

目的研究外侧裂区脑挫裂伤的机理和治疗方法。方法对31例外侧裂区脑挫裂伤病例的临床资料进行回顾性分析。结果保守治疗14例,手术治疗17例,死亡5例,3￣6月后按GOS评分植物生存2例,重残3例,中残8例,良好13例。结论及时解除血管压迫可提高临床治疗效果。     

The use of segmented regression for evaluation of an interrupted time series study involving complex intervention: the CaPSAI project experience

Health Services and Outcomes Research Methodology - An interrupted time series with a parallel control group (ITS-CG) design is a powerful quasi-experimental design commonly used to evaluate the...     

Immunogenicity,safety and reactogenicity of ROTAVAC® in healthy infants aged 6–8 weeks in Vietnam

BackgroundROTAVAC® is derived from human 116E rotavirus (RV) neonatal strain. In this study, we evaluated the immunogenicity, safety and reactogenicity of ROTAVAC® in Vietnam.MethodWe conducted a phase IV clinical trial in healthy infants aged 6–8 weeks using the complete regimen of ROTAVAC® with three doses. Serum anti-RV IgA was measured by enzyme-linked immunosorbent assay to assess the geometric mean concentration in infants who received the complete regimen of the vaccine.ResultsA total of 360 participants were enrolled in this clinical trial. The mean age ± standard deviation at enrollment was 6.9 ± 0.6 weeks. The anti-RV IgA titer was 4.01 ± 3.74 mg/ml pre-vaccination and substantially increased to 29.27 ± 80.64 mg/ml post-vaccination. The value of logIgA significantly increased (p = 0.003) from 0.28 ± 0.79 to 1.03 ± 0.54. The proportion of participants with equal to and greater than 3-fold and 4-fold shifts in pre- to post-vaccination antibody titer (IgA) were 55.4% and 48.3%, respectively. No adverse events or serious adverse events were recorded immediately within 30 min after the administration of each dose. The most common adverse events within 14 days after each visit were fever, unusual crying and irritability. Other adverse events occurred at a low rate, and no case of intussusception was noted.ConclusionsThe complete regimen of ROTAVAC® demonstrated an immunological response with clinically acceptable safety profile. Post-completion of this study, ROTAVAC® is now a WHO-prequalified vaccine and available in Vietnam.     

Inhibitory effect of 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H - imidazole on HCMV DNA replication and permissive infection.

We found that Human Cytomegalovirus (HCMV) infection of human fibroblasts resulted in a dramatic increase in p38 mitogen-activated protein kinase (MAPK) phosphorylation. Recently, drug mediated inhibition of p38 has been demonstrated to exhibit anti-viral activity against HIV (Shapiro, L., Heidenreich, K.A., Meintzer, M.D. and Dinarello, C.A., 1998. Role of p38 mitogen-activated protein kinase in HIV type 1 production in vitro. Proc. Natl. Acad. Sci. USA. 95, 7422-7426). Therefore, we examined the effect of a specific p38 kinase inhibitor on HCMV infection. Inhibiting p38 activity in HCMV infected cells by treating cells with 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole; (FHPI), a p38 inhibitor drug, prevented permissive HCMV infection as measured by plaque assay. In the presence of FHPI, HCMV immediate early gene expression was slightly lower at early times of infection, but there was no inhibition of expression of the early gene UL-84, an HCMV protein essential for viral replication. However, FHPI inhibited HCMV DNA replication and late gene expression. The inhibitory effect of FHPI was reversible, as demonstrated by the induction of HCMV replication upon withdrawal of FHPI. Our data describes FHPI as a novel anti-HCMV compound that inhibits synthesis/activation of cellular and/or viral factors required for initiation of HCMV DNA replication.     

Efficacy and safety evaluation of human reovirus type 3 in immunocompetent animals: racine and nonhuman primates.

PURPOSE: Human reovirus type 3 has been proposed to kill cancer cells with an activated Ras signaling pathway. The purpose of this study was to investigate the efficacy of reovirus in immunocompetent glioma animal models and safety/toxicity in immunocompetent animals, including nonhuman primates. EXPERIMENTAL DESIGN: Racine glioma cells 9L and RG2 were implanted s.c. or intracranially in Fisher 344 rats with or without reovirus antibodies, followed by treatment of reovirus. To study whether reovirus kills contralateral tumors in the brain and to determine viral distribution, we established an in situ dual tumor model followed by reovirus intratumoral inoculation only into the ipsilateral tumor. To evaluate neurotoxicity/safety of reovirus, Cynomolgus monkeys and immunocompetent rats were given intracranially with reovirus, and pathological examination and/or behavioral studies were done. Viral shedding and clinical biochemistry were systematically studied in monkeys. RESULTS: Intratumorally given reovirus significantly suppressed the growth of both s.c. and intracranially tumors and significantly prolonged survival. The presence of reovirus-neutralizing antibodies did not abort the reovirus' antitumor effect. Reovirus inhibited glioma growth intracranially in the ipsilateral but not the contralateral tumors; viral load in ipsilateral tumors was 15 to 330-fold higher than the contralateral tumors. No encephalitis or behavioral abnormalities were found in monkeys and rats given reovirus intracranially. No treatment-related clinical biochemistry changes or diffuse histopathological abnormality were found in monkeys inoculated intracranially with Good Manufacturing Practice prepared reovirus. Microscopic changes were confined to the region of viral inoculation and were dose related, suggesting reovirus intracranially was well tolerated in nonhuman primates. CONCLUSIONS: These data show the efficacy and safety of reovirus when it is used in the treatment of gliomas in immunocompetent hosts. Inoculation of reovirus into the brain of nonhuman primates did not produce significant toxicities.     

Effect of pregnancy, menopause and hormone substitution therapy on disseminated systemic lupus erythematosus

EXACERBATIONS DURING PREGNANCY: Clinical and experimental data have clearly evidenced the influence of hormones on the course of systemic lupus erythematosus. In prospective studies of pregnant women, an exacerbation is observed in 57% to 60% of the cases. It can be severe in 10% of the cases and occur in the post partum in 7%. For most patients, the exacerbation is moderate and has no unfavorable effect on the outcome of pregnancy. In case of renal involvement, it is difficult to differentiate an intricated HELPP syndrome. MARKERS AND RISK FACTORS: Low complement and elevated anti-DNA levels are distinctive markers. Earlier renal involvement and hypertension are important prognostic factors, particularly when the lupus begins during pregnancy. However, when serum creatinine is lower than 100 mumol/l at pregnancy onset in patients in remission, pregnancy does not alter renal function. An association with antiphospholipid antibodies increases the risk for the fetus and the kidney function. TREATMENT: Optimal treatment remains to be defined. Commonly, patients are given aspirin, heparin in case of a history of thromboembolism, or both. The rate of success currently exceeds 70%. The risk of thromboembolism in the peri or post partum period requires anticoagulant treatment. Outside pregnancy: Ovulation induction raises two risks: triggering a lupus flare-up and thrombosis, particularly for patients with antiphospholipid antibodies. The influence of menopause and hormone replacement therapy remains poorly understood.     

Recent advances in diagnosis and management of pulmonary hypertension in chronic lung disease

Pulmonary hypertension with elevated pulmonary vascular resistance is a common cardiovascular complication associated with increased morbidity and mortality in preterm infants with chronic lung disease. Injury to the developing pulmonary circulation results in structural and functional abnormalities of the pulmonary vasculature. Animal studies have demonstrated that disruption of angiogenesis may contribute to the failure of normal alveolarisation in chronic lung disease. Levels of vascular endothelial growth factor in bronchoalveolar lavage fluid are lower in infants with chronic lung disease compared to preterm controls. Supplemental oxygen is commonly used to prevent and treat pulmonary hypertension, although optimal arterial oxygen saturation levels remain uncertain. Other vasodilators such as inhaled nitric oxide appear promising, but as yet have not been evaluated in the form of randomised controlled trials. Further studies are required to investigate the long-term effectiveness of pulmonary vasodilator therapy.