Effective d-penicillamine treatment of an early diagnosed patient with Wilson's disease

European Journal of Pediatrics -     

Development and degeneration of retina in rds mutant mice: Light microscopy

Changes during the development and degeneration of the retina in 020/A mice, which are homozygous for the newly reported rds (retinal degeneration slow), gene were studied by histological and enzyme-histochemical methods with Balb/c mice carrying the normal allele as control. During normal development the total thickness of the retina grows from the time of birth till the age of 21 days and thereafter gradually diminishes, while the thicknesses of the component layers show a characteristic and differential change in course of their histogenesis. In the normal retina the perikarya of the cones are more frequent in the central than in the peripheral areas. The cone frequency in the central retina, but not in the periphery, increases with age and implies selective loss of rod cells in older animals. In the homozygous rds mice, the receptor layer remains rudimentary, but the other retinal layers show a normal trend of growth during the first 2 weeks after birth. Thereafter the morphological layers containing visual cell structures—the receptor, the outer nuclear, and the outer plexiform layers—begin to reduce. The loss of visual cells is readily marked by the reduction of the outer nuclear layer and is first evident at 2 weeks after birth. Degeneration is more rapid up to the age of 2–3 months, when the outer nuclear layer is reduced to half of its original thickness; thereafter degeneration progresses more slowly. The receptor and the outer plexiform layers are also simultaneously reduced. At 9 months, the peripheral parts of the retina, and at 12 months, the entire retina is completely lacking in visual cells. In the central retina of the mutant, rod and cone cell populations are equally affected up to the age of 6 months, as their relative frequency remains similar to the normal. In the peripheral retina, where cell loss is more pronounced, and in the central retina at 9 months an increase in relative frequency of cones is recorded and indicate increased susceptibility of the rods to later degenerative changes. The inner parts of the retina, including inner nuclear, inner plexiform, and ganglion cell layers, remain morphologically unaffected until irregular vascularization follows total loss of visual cells. The pigment epithelium is also affected at this late stage and appears depleted and patchy. In the normal retina, macrophages which are positively stained for the enzyme N-acetyl-β-glucosaminidase appear in the inner layers with the growth of the retinal vasculature. In the mutant, increased frequency and stainability of the macrophages are discernible in the inner retina at 11 days. The macrophages migrate outwards and are observed in the outer nuclear layer and in the optic ventricle during the period of degeneration. These findings are compared with the observations in the other retinal degeneration mutants in rodents, and in retinitis pigmentosa in humans. The suitability of the rds mice as an animal model system for the human disease is emphasized.     

Experimental radiation injury: combined MR imaging and spectroscopy

A model of radiation injury to the brain was developed in the cat. Definite radiation changes were demonstrated at magnetic resonance (MR) imaging in four of six cats. These changes consisted of high-intensity abnormalities on images obtained with a long repetition time (TR) and a long echo time (TE), which were initially noted 208-285 days after irradiation. These changes were associated with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) enhancement on short TR and inversion-recovery (IR) pulse sequences. Gd-DTPA enhancement and the high intensity on the long TR/TE images were identified at the same time and became more prominent throughout the study. Chemical-shift imaging and phosphorus spectroscopy demonstrated no notable changes despite clear-cut MR evidence of abnormalities. Sodium imaging was positive in one case. Correlation of MR and pathologic findings revealed areas of radiation necrosis and wallerian degeneration that corresponded to areas of Gd-DTPA enhancement on short TR and IR images and to areas of high intensity on long TR/TE images. Peripheral to the areas of Gd-DTPA enhancement were nonenhanced zones of high-signal-intensity abnormality on long TR/TE images, which represented regions of demyelination without necrosis. Gd-DTPA-enhanced proton imaging was the most sensitive method for detecting radiation damage in this animal model.     

Drug resistance is uncommon in pregnant women with low viral loads taking zidovudine monotherapy to prevent perinatal HIV transmission

Zidovudine monotherapy is used to reduce perinatal HIV transmission in women with low viral loads. There are few data on the risk of drug resistance in this select cohort of women. We determined the prevalence of newly acquired mutations conferring reduced sensitivity to zidovudine after exposure during pregnancy, and found that the development of mutations was uncommon and was restricted to women treated before 1998 who had higher baseline viral loads than those currently recommended monotherapy.