Multi-system neurological disease is common in patients with OPA1 mutations

Additional neurological features have recently been described in seven families transmitting pathogenic mutations in OPA1, the most common cause of autosomal dominant optic atrophy. However, the frequency of these syndromal `dominant optic atrophy plus` variants and the extent of neurological involvement have not been established. In this large multi-centre study of 104 patients from 45 independent families, including 60 new cases, we show that extra-ocular neurological complications are common in OPA1 disease, and affect up to 20% of all mutational carriers. Bilateral sensorineural deafness beginning in late childhood and early adulthood was a prominent manifestation, followed by a combination of ataxia, myopathy, peripheral neuropathy and progressive external ophthalmoplegia from the third decade of life onwards. We also identified novel clinical presentations with spastic paraparesis mimicking hereditary spastic paraplegia, and a multiple sclerosis-like illness. In contrast to initial reports, multi-system neurological disease was associated with all mutational subtypes, although there was an increased risk with missense mutations [odds ratio = 3.06, 95% confidence interval = 1.44-6.49; P = 0.0027], and mutations located within the guanosine triphosphate-ase region (odds ratio = 2.29, 95% confidence interval = 1.08-4.82; P = 0.0271). Histochemical and molecular characterization of skeletal muscle biopsies revealed the presence of cytochrome c oxidase-deficient fibres and multiple mitochondrial DNA deletions in the majority of patients harbouring OPA1 mutations, even in those with isolated optic nerve involvement. However, the cytochrome c oxidase-deficient load was over four times higher in the dominant optic atrophy + group compared to the pure optic neuropathy group, implicating a causal role for these secondary mitochondrial DNA defects in disease pathophysiology. Individuals with dominant optic atrophy plus phenotypes also had significantly worse visual outcomes, and careful surveillance is therefore mandatory to optimize the detection and management of neurological disability in a group of patients who already have significant visual impairment.

Parafoveal letter recognition at reduced contrast in normal aging and in patients with risk factors for AMD

Background Patients with early age-related maculopathy ( ARM) do not necessarily show obvious morphological signs or functional impairment. Many have good visual acuity, yet complain of decreased visual performance. The aim of this study was to investigate the aging effects on performance of parafoveal letter recognition at reduced contrast, and defects caused by early ARM and normal fellow eyes of patients with unilateral age-related macular degeneration (nfAMD). Methods Testing of the central visual field (8 radius) was performed by the Macular Mapping Test (MMT) using recognition of letters in 40 parafoveal target locations at four contrast levels (5, 10, 25 and 100%). Effects of aging were investigated in 64 healthy subjects aged 23 to 76 years (CTRL). In addition, 39 eyes (minimum visual acuity of 0.63; 20/30) from 39 patients with either no visible signs of ARM, while the fellow eye had advanced age-related macular degeneration (nfAMD; n=12), or early signs of ARM (eARM; n=27) were examined. Performance was expressed summarily as a ""field score"" (FS). Results Performance in the MMT begins to decline linearly with age in normal subjects from the age of 50 and 54 years on, at 5% and 10% contrast respectively. The differentiation between patients and CTRLs was enhanced if FS at 5% was analyzed along with FS at 10% contrast. In 8/12 patients from group nfAMD and in 18/27 from group eARM, the FS was statistically significantly lower than in the CTRL group in at least one of the lower contrast levels. Conclusion Using parafoveal test locations, a recognition task and diminished contrast increases the chance of early detection of functional defects due to eARM or nfAMD and can differentiate them from those due to aging alone.

Analyses of cataract surgery performed by the Unified Health System in Brazil, 2006-2007

Objective. Estimate cataract surgical rates (CSR) for Brazil and each federal unit in 2006 and 2007 based on the number of surgeries performed by the Unified Health System to help plan a comprehensive ophthalmology network in order to eliminate cataract blindness in compliance with the target set by the World Health Organization (WHO) of 3 000 cataract surgeries per million inhabitants per year. Methods. This descriptive study calculates CSR by using the number of cataract surgeries carried out by the Brazilian Unified Health System for each federal unit and estimates the need for cataract surgery in Brazil for 2006-2007, with official population data provided by the Brazilian Institute of Geography and Statistics. The number of cataract surgeries was compared with the WHO target. Results. To reach the WHO goal for eliminating age-related cataract blindness in Brazil, 560 312 cataract surgeries in 2006 and 568 006 surgeries in 2007 needed to be done. In 2006, 179 121 cataract surgeries were done by the Unified Health System, corresponding to a CSR of 959 per million population; in 2007, 223 317 were performed, with a CSR of 1 179. With the Brazilian Council of Ophthalmology estimation of 165 000 surgeries each year by the non-public services, the CSR for Brazil would be 1 842 for 2006 and 2 051 for 2007. The proportions needed to achieve the proposed target were 38.6% in 2006 and 31.6% in 2007. Conclusions. Human resources, technical expertise, and equipment are crucial to reach the WHO goal. Brazil has enough ophthalmologists but needs improved planning and infrastructure in order to eliminate the problem, aspects that require greater financial investment and stronger political commitment.

High intake of fruits and vegetables predicts weight loss in Brazilian overweight adults

To determine whether changes in dietary intakes predict weight loss, we studied 80 overweight adults who attended a nutritional counseling program during 6 months of follow-up at a primary health care center in Brazil. Habitual diet was assessed using a validated food frequency questionnaire at baseline and after 6 months. The mean age (+/-SD) of the participants was 46.5 +/- 9.5 years, and their mean body mass index was 29 +/- 3 kg/m(2) at baseline. After 6 months, the differences in body weight and fruit/vegetable intake were -1.4 +/- 3 kg and 109 +/- 320 g daily, respectively. Using multiple linear regression models adjusted for age, sex, changes in walking time, and total energy intake, the increased intake of dietary fiber from fruits/vegetables was associated with a greater weight loss (beta 1 [95% confidence interval (CI)] = -0.180 [-0.269, -0.0911) after 6 months of follow-up. Similar results were observed for increased intake of vegetables (beta 1 [95% CI] = -0.00497 [-0.008, -0.0021) and fruits (beta 1 [95% CI] = -0.00290 [-0.005, -0.001]) as predictors of weight loss. The increase of 100 g/d of vegetables and fruits represented a body weight loss of 500 and 300 g after 6 months, respectively (P <.05). Our findings support the relevance of increased intakes of fruits and vegetables that may help avoid weight gain in overweight adults. (C) 2008 Elsevier Inc. All rights reserved.

The connective tissue of the adductor canal - a morphological study in fetal and adult specimens

The adductor canal is a conical or pyramid-shaped pathway that contains the femoral vessels, saphenous nerve and a varying amount of fibrous tissue. It is involved in adductor canal syndrome, a claudication syndrome involving young individuals. Our objective was to study modifications induced by aging on the connective tissue and to correlate them to the proposed pathophysiological mechanism. The bilateral adductor canals and femoral vessels of four adult and five fetal specimens were removed en bloc and analyzed. Sections 12 mu m thick were obtained and the connective tissue studied with Sirius Red, Verhoeff, Weigert and Azo stains. Scanning electron microscopy (SEM) photomicrographs of the surfaces of each adductor canal were also analyzed. Findings were homogeneous inside each group. The connective tissue of the canal was continuous with the outer layer of the vessels in both groups. The pattern of concentric, thick collagen type I bundles in fetal specimens was replaced by a diffuse network of compact collagen bundles with several transversal fibers and an impressive content of collagen III fibers. Elastic fibers in adults were not concentrated in the thick bundles but dispersed in line with the transversal fiber system. A dynamic compression mechanism with or without an evident constricting fibrous band has been proposed previously for adductor canal syndrome, possibly involving the connective tissue inside the canal. The vessels may not slide freely during movement. These age-related modifications in normal individuals may represent necessary conditions for this syndrome to develop.

Dehydroepiandrosterone protects against oxidative stress-induced endothelial dysfunction in ovariectomized rats

Cardiovascular disease is less frequent in premenopausal women than in age-matched men or postmenopausal women. Moreover, the marked age-related decline in serum dehydroepiandrosterone (DHEA) level has been associated to cardiovascular disease. The aim of this study was to evaluate the effects of DHEA treatment on vascular function in ovariectomized rats. At 8 weeks of age, female Wistar rats were ovariectomized (OVX) or sham (SHAM) operated and 8 weeks after surgery both groups were treated with vehicle or DHEA (10 mg kg-1 week-1) for 3 weeks. Aortic rings were used to evaluate the vasoconstrictor response to phenylephrine (PHE) and the relaxation responses to acetylcholine (ACh) and sodium nitroprusside (SNP). Tissue reactive oxygen species (ROS) production and SOD, NADPH oxidase and eNOS protein expression were analysed. PHE-induced contraction was increased in aortic rings from OVX compared to SHAM, associated with a reduction in NO bioavailability. Furthermore, the relaxation induced by ACh was reduced in arteries from OVX, while SNP relaxation did not change. The incubation of aortic rings with SOD or apocynin restored the enhanced PHE-contraction and the impaired ACh-relaxation only in OVX. DHEA treatment corrected the increased PHE contraction and the impaired ACh-induced relaxation observed in OVX by an increment in NO bioavailability and decrease in ROS production. Besides, DHEA treatment restores the reduced Cu/Zn-SOD protein expression and eNOS phosphorylation and the increased NADPH oxidase protein expression in the aorta of OVX rats. The present results suggest an important action of DHEA, improving endothelial function in OVX rats by acting as an antioxidant and enhancing the NO bioavailability.