Pseudoxanthoma elasticum (PXE) is a hereditary disorder of connective tissue with skin, cardiovascular, and visual involvement. In familial cases, PXE usually segregates in an autosomal recessive ...fashion. The aim of this manuscript is to describe an efficient strategy for DNA diagnosis of PXE. The two most frequent mutations, R1141X and an ABCC6 del exons 23-29, as well as a core set of mutations, were identified by restriction enzyme digestion and size separation on agarose gels. Next, in the remaining patient group in which only one or no mutant allele was found, the complete coding sequence was analyzed using denaturing high-performance liquid chromatography (dHPLC). All variations found were confirmed by direct DNA sequencing. Finally, Southern blot was used to investigate the potential presence of small or large deletions. Twenty different mutations, including two novel mutations in the ABCC6 gene, were identified in 80.3% of the 76 patients, and 58.6% of the 152 ABCC6 alleles analyzed. With this strategy, 70 (78.7%) out of 89 mutant alleles could be detected within a week. We conclude that this strategy leads to both reliable and time-saving screening for mutations in the ABCC6 gene in sporadic cases and in families with PXE.
To determine the prevalence of chorioretinal lesions and optic disc edema after heart transplantation and to study potential associations.
One hundred one patients who had undergone heart ...transplantation at one institution and 19 patients prior to heart transplantation underwent ophthalmological examination, including fundus photography. The prevalence of fundus lesions was then compared between the two groups.
With a standardized protocol, the presence of optic disc edema, chorioretinal hyperpigmentation and depigmentation, retinal hemorrhages, cotton-wool lesions, and arteriovenous nicking was graded on color transparencies.
The prevalence of optic disc edema and hypopigmentations was significantly higher among the transplant recipients than among the patients prior to heart transplantation (31% vs 5%, P = .01, and 55% vs 11%, P < .001, respectively). Hyperpigmentation was only present in patients after transplantation (15% vs 0%, P = .06). Heart transplant recipients showed an increased risk of hyperpigmentations after 2.5 years. Acute rejection episodes were not associated with posterior pole lesions.
Common posterior pole lesions after heart transplantation are optic disc edema and pigmentary changes. Although visual acuity does not seem severely impaired, further longitudinal study is necessary to evaluate the long-term significance of these lesions.
A low diastolic blood pressure has been associated with increased cardiovascular risk. The following proposed mechanisms underlie this phenomenon: a low diastolic pressure that compromises coronary ...blood flow, a low diastolic pressure that is due to deteriorating health, and a low diastolic pressure that is a consequence of stiffening of the large arteries. Atherosclerosis may be the link between stiffening of the arteries, a low diastolic pressure, and an increased cardiovascular risk.
To study whether a low diastolic blood pressure in older subjects is a reflection of atherosclerosis.
The Rotterdam (the Netherlands) Study is a population-based follow-up study of 7983 subjects (age, > or = 55 years) who are living in the suburb of Ommoord of Rotterdam. Baseline measurements included ultrasonographic evaluation of the carotid arteries, measurement of blood pressure, and determination of other cardiovascular risk factors. The main cross-sectional analyses were performed among 930 subjects who currently were not using blood pressure-lowering drugs.
A J-shaped association of the intima-media thickness of the common carotid artery with diastolic blood pressure was found with a nadir from 60 to 69 mm Hg. The intima-media thickness was increased in subjects with a diastolic pressure that was less than 60 mm Hg compared with that in subjects with a diastolic pressure that was between 60 and 69 mm Hg (a difference of 0.033 mm 95% confidence limits; 0.001, 0.065). Beyond a diastolic pressure of 70 mm Hg, a gradual increase in the intima-media thickness was observed. The association was most pronounced among subjects with relatively high pulse pressures.
Results of the present study indicate the existence of a J-shaped association between carotid atherosclerosis and diastolic pressure. These findings support the hypothesis that in elderly subjects, a low diastolic pressure may be a reflection of widespread atherosclerosis.
OBJECTIVES To evaluate the natural course of age-related maculopathy (ARM) and to assess the incidence and absolute risk of its final stage, age-related macular degeneration (AMD). METHODS In a ...population-based prospective cohort study of 6418 persons 55 years and older, we studied the incidence and natural course of ARM. Subjects underwent identical examinations, including stereoscopic fundus photography, at baseline and at 2.0 and 6½ years' follow-up. Age-related maculopathy was graded according to the International Classification and Grading System for ARM and AMD, and stratified into 5 exclusive stages. Incidence was expressed in rates and 5-year absolute risks. RESULTS At follow-up, 47 new cases of AMD were identified, with a ratio of neovascular-atrophic AMD of 1.4:1. The 5-year risk of AMD increased with more severe stages to 28.0% for subjects 55 years and older with indistinct drusen and pigmentary irregularities (stage 3). Age, but not sex, independently increased this risk to a maximum of 42.0% for subjects with stage 3 ARM who were 80 years and older. Individual ARM fundus signs that predicted best the development of AMD were 10 or more large drusen (≥125 µm) and 10% or more of the grid area covered by drusen. Subjects who developed atrophic AMD showed no significant (P = .25) differences in baseline fundus signs and natural course compared with subjects who developed neovascular AMD. CONCLUSIONS We provided the absolute risk of AMD as a function of age and early ARM fundus signs, and showed that both are prominent independent risk factors. The progression of ARM stages follows, after the appearance of the first soft drusen, a distinct course at a gradual pace that accelerates with increasing age.Arch Ophthalmol.2003;121:519-526
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