Hereditary Cerebral Hemorrhage with Amyloidosis-Dutch Type (HCHWA-D): I - A Review of Clinical, Radiologic and Genetic Aspects

Hereditary cerebral hemorrhage with amyloidosis - Dutch type (HCHWA-D) is an autosomal dominant disease caused by deposition of β-amyloid in the leptomeningeal arteries and cortical arterioles, in addition to preamyloid deposits and amyloid plaques in the brain parenchyma.
The disease is due to a point mutation at codon 693 of the amyloid precursor protein (βPP) gene at chromosome 21. Since this point mutation is diagnostic for HCHWA-D, presymptomatic testing is feasible and offered, together with genetic counselling and psychological support, to subjects at risk. HCHWA-D is clinically characterized by recurrent strokes, in addition to dementia, which can occur after the first stroke but also preceding it. Radiological studies revealed focal lesions (hemorrhages, hemorrhagic and non-hemorrhagic infarctions) and diffuse white matter damage. Diffuse white matter hyperintensities on MRI are an early symptom of HCHWA-D since they have been found on MRI scans of subjects who had not suffered a stroke.
The presence of the diagnostic point mutation makes HCHWA-D a useful model to study the effects of cerebral amyloid angiopathy in vivo. The characteristic pathological abnormalities and its implications for Alzheimer's disease will be discussed in Part II of this article     

Effect of postpartum maternal or neonatal vitamin A supplementation on infant mortality among infants born to HIV-negative mothers in Zimbabwe

BACKGROUND: Young infants are at risk of vitamin A deficiency. Supplementation of breastfeeding mothers improves the vitamin A status of their infants, but there are no data regarding its effect on infant mortality, and data on the effect of directly supplementing infants during the first few weeks of life are conflicting. OBJECTIVE: The objective was to measure the effect on infant mortality of supplementing neonates and their HIV-negative mothers with single, large doses of vitamin A during the immediate postpartum period. DESIGN: A randomized, placebo-controlled, 2-by-2 factorial design trial was conducted in 14,110 mothers and their infants; 9208 of the mothers were HIV-negative at delivery, remained such during the postpartum year, and were retained in the current analysis. The infants were randomly assigned within 96 h of delivery to 1 of 4 treatment groups: mothers and infants received vitamin A (Aa), mothers received vitamin A and infants received placebo (Ap), mothers received placebo and infants received vitamin A (Pa), and both mothers and infants received placebo (Pp). The vitamin A dose in the mothers was 400,000 IU and in the infants was 50,000 IU. The mother-infant pairs were followed to 12 mo. RESULTS: Hazard ratios (95% CI) for 12 mo mortality among infants in the maternal-supplemented and infant-supplemented groups were 1.17 (0.87, 1.58) and 1.08 (0.80, 1.46), respectively. Hazard ratios (95% CI) for the Aa, Ap, and Pa groups compared with the Pp group were 1.28 (0.83, 1.98), 1.27 (0.82, 1.97), and 1.18 (0.76, 1.83), respectively. These data indicate no overall effect. Serum retinol concentrations among a subsample of women were similar to reference norms. CONCLUSION: Postpartum maternal or neonatal vitamin A supplementation may not reduce infant mortality in infants of HIV-negative women with an apparently adequate vitamin A status.     

HIV-1 and HIV-2 prevalence and associated risk factors among postnatal women in Harare, Zimbabwe

Studies of antenatal women form the predominant source of data on HIV-1 prevalence in Africa. Identifying factors associated with prevalent HIV is important in targeting diagnostic services and care. Between November 1997 and January 2000, 14,110 postnatal women from Harare, Zimbabwe were tested by ELISAs reactive to both HIV-1 and HIV-2; a subset of positive samples was confirmed with assays specific for HIV-1 and HIV-2. Baseline characteristics were elicited and modelled to identify risk factors for prevalent HIV infection. HIV-1 and HIV-2 prevalences were 32.0% (95% CI 31.2-32.8) and 1.3% (95% CI 1.1-1.5), respectively; 4% of HIV-1-positive and 99% of HIV-2-positive women were co-infected. HIV-1 prevalence increased from 0% among 14-year-olds to >45% among women aged 29-31 years, then fell to <20% among those aged>40 years. In multivariate analyses, prevalence increased with parity, was lower in married women than in single women, divorcees and widows, and higher in women with the lowest incomes and those professing no religion. Adjusted HIV-1 prevalence increased during 1998 and decreased during 1999. Age modified the effects of parity, home ownership and parental education. Among older women, prevalence was greater for women who were not homeowners. Among younger women, prevalence increased with parity and low parental education. None of these factors distinguished women co-infected with HIV-2 from those infected with HIV-1 alone. Prevalent HIV-1 infection is associated with financial insecurity and weak psychosocial support. The ZVITAMBO study apparently spanned the peak of the HIV-1 epidemic among reproductive women in Harare.     

SarCNU在MGMT耐药基因高表达荷瘤鼠中抗瘤作用分析

目的 ２－氯乙基－３－肌氨酸酰胺－１－亚硝脲（ＳａｒＣＮＵ）是一类新型亚硝脲类抗癌药,探讨其对ＭＧＭＴ耐药基因高表达胶质瘤的疗效。方法 腹腔注射ＳａｒＣＮＵ（５００ｍｇ／ｍ＾２）,ＢＣＮＵ（４０ｍｇ／ｍ＾２）,Ｏ＾６－ＢＧ（３００ｍｇ／ｍ＾２）,观察其在动物体内胶质瘤的生长情况。结果 ＳａｒＣＮＵ处理组生长缓延３４．７天,ＢＣＮＵ组生长延缓２０．７５天,差异有显著性,ＳａｒＣＮＵ与Ｏ＾６－ＢＧ联合     

DIFFICULTIES AND DILEMMAS IN THE MANAGEMENT OF CONGENITAL ANOMALIES IN TWIN PREGNANCY

Both the incidence of twin pregnancy and the demand for prenatal diagnosis are increasing. Unfortunately, biochemical screening and ultrasound scanning are less reliable for prenatal diagnosis in twin pregnancies than in singletons. Amniocentesis and chorionic villous biopsy are usually diagnostic in singleton pregnancies but may be marred by sampling errors in twin gestations. Where a congenital anomaly has been diagnosed in a twin pregnancy, difficult decisions may have to be made, especially if one twin is unaffected. In these cases, special skills are required to ensure that adequate information, psychological support and optimal medical care are provided.