Structural and molecular changes in the aging choroid: implications for age-related macular degeneration.

Age-related macular degeneration (AMD) is a devastating disease-causing vision loss in millions of people around the world. In advanced stages of disease, death of photoreceptor cells, retinal pigment epithelial cells, and choroidal endothelial cells (CECs) are common. Loss of endothelial cells of the choriocapillaris is one of the earliest detectable events in AMD, and, because the outer retina relies on the choriocapillaris for metabolic support, this loss may be the trigger for progression to more advanced stages. Here we highlight evidence for loss of CECs, including changes to vascular density within the choriocapillaris, altered abundance of CEC markers, and changes to overall thickness of the choroid. Furthermore, we review the key components and functions of the choroid, as well as Bruch's membrane, both of which are vital for healthy vision. We discuss changes to the structure and molecular composition of these tissues, many of which develop with age and may contribute to AMD pathogenesis. For example, a crucial event that occurs in the aging choriocapillaris is accumulation of the membrane attack complex, which may result in complement-mediated CEC lysis, and may be a primary cause for AMD-associated choriocapillaris degeneration. The actions of elevated monomeric C-reactive protein in the choriocapillaris in at-risk individuals may also contribute to the inflammatory environment in the choroid and promote disease progression. Finally, we discuss the progress that has been made in the development of AMD therapies, with a focus on cell replacement.

When is facial diplegia regarded as a variant of Guillain-Barré syndrome?

A variant of Guillain-Barré syndrome (GBS) with predominant manifestation of facial diplegia (FD) has been described recently. This study aimed to characterize and determine the incidence of this FD-predominant GBS variant. The clinical and serological information of 900 consecutive patients were reviewed. In total, eight patients were identified between January 2007 and December 2010 as having FD accompanied by some features of GBS. These features were subjective sensory symptoms such as distal paresthesia (7/8, 88%), albumin-cytological (A/C) dissociation (7/8, 88%), antecedent infection (6/8, 75%), and minor nerve conduction study (NCS) abnormalities (5/7, 71%). One patient presented with the typical NCS feature of demyelinating neuropathy. Only two patients exhibited areflexia (2/8, 25%). None of the patients possessed any anti-ganglioside antibodies; however, the serum of two patients was positive for anti-mycoplasma antibody (2/6, 33%). FD variant of GBS occurred in less than 1% of our dataset. FD can be a regional variant of GBS when it is accompanied by supporting features, such as subjective tingling, A/C dissociation, and minor NCS abnormalities.

Phenotypic variation of a Thr704Met mutation in skeletal sodium channel gene in a family with paralysis periodica paramyotonica.

OBJECTIVES: Patients with paralysis periodica paramyotonica exhibit a clinical syndrome with characteristics of both hyperkalaemic periodic paralysis and paramyotonia congenita. In several types of periodic paralysis associated with hyperkalaemia, mutations in the skeletal muscle sodium channel (SCN4A) gene have been previously reported. Phenotypic variations of mutations in SCN4A, however, have not been described yet. The present study aimed to evaluate genetic variations in a family with clinical and electrophysiological characteristics of paralysis periodica paramyotonia. METHODS: Seven members of a family affected with symptoms of paralysis periodica paramyotonia were studied by electrophysiological and genetic analyses. There were increased serum potassium concentrations in four members during paralytic attacks induced by hyperkalaemic periodic paralysis provocation tests. Short exercise tests before and after cold immersion were carried out in four patients to distinguish electrophysiological characteristics of hyperkalaemic periodic paralysis and paramyotonia. Sequencing analyses of SCN4A were performed on one patient and a normal control to identify polymorphisms. Restriction fragment length polymorphism (RFLP) analysis was then performed at the identified polymorphic sites. RESULTS: Electrophysiological studies showed both exercise sensitivity and temperature sensitivity. Compound motor action potential (CMAP) amplitudes were decreased (7.3%-28.6%) after short exercise tests. The CMAP amplitudes were even more severely decreased (21.7%-56.5%) in short exercise tests after cold exposure. Three polymorphic sites, Gln371Glu, Thr704Met, and Aspl376Asn were identified in SCN4A. RFLP analyses showed that all affected patients carried the Thr704Met mutation, whereas unaffected family members and a normal control did not. CONCLUSION: Phenotypic variation of the Thr704Met mutation, which was previously reported in patients with hyperkalaemic periodic paralysis, is described in a family affected with paralysis periodica paramyotonia.

Analysis of chromosome aberrations in nuclear-power-plant workers considering the lifetime of lymphocytes.

PURPOSE: To analyse chromosome aberrations in nuclear-power-plant workers taking account of the mean lifetime of lymphocytes (MLTL). MATERIALS AND METHODS: Analysis of chromosome aberrations was performed on peripheral lymphocytes from 395 nuclear-power-plant workers and 135 controls. An equivalent acute dose (EAD) was calculated utilizing MLTL values of either 4.3 or 10 years. RESULTS: Using an MLTL value of 10 years produced an EAD range of 0.O1 mSv -182mSv(mean 46.6mSv), while using an MLTL, of 4.3 years produced results ranging from 0.01 mSv to 86.2 mSv (mean 23.4 mSv). A significant increase of chromosome-type exchange by the equivalent acute dose was observed using an MLTL of either 10 or 4.3 years when including the control in the analysis, but a significant increase was not seen when only the exposed was considered. A significant increase of chromosome-type deletion by EAD was seen even when only the exposed group was considered. CONCLUSIONS: EAD values based on an MLTL of either 4.3 or 10 years, as well as cumulative dose, showed no significant association with chromosome aberrations, when radiation workers only were analysed. The narrow dose range examined in this study might have contributed to this finding.