Association of polymorphisms in the Tau and Saitohin genes with Parkinson's disease

BACKGROUND: The Saitohin gene has recently been identified in intron 9 of the Tau gene. Because an association between Parkinson's disease and Tau has been described, Saitohin represents a candidate gene for Parkinson's disease. OBJECTIVE: To test these two genes for their association with Parkinson's disease in a large community based case-control study. RESULTS: Cases (n = 208) were more often homozygotes for the Tau H1 haplotype than controls (n = 483; odds ratio (OR) = 1.71 (95% confidence interval, 1.20 to 2.43); p = 0.003), and the saitohin Q allele was in complete linkage disequilibrium with the H1 haplotype. This association was stronger among cases with Parkinson's disease onset below 65 years (< or =65 years: OR = 2.52 (1.49 to 4.25); p<0.001) than among those with older onset (>65 years: OR = 1.20 (0.73 to 1.98); p<0.47). CONCLUSIONS: The data suggest that there is a functional polymorphism at this locus involved in Parkinson's disease.     

Atherosclerosis--the role of nitric oxide

ATHEROSCLEROSIS: Currently regarded as a multifactorial disease, atherosclerosis involves several factor including: oxidized LDL, endothelial cells, macrophages, immune cells, vascular smooth muscle cells. The endothelium appears to play a key role through the production of vasomotor, antiaggregate and leukocyte antiadhesion molecules. NITRIC OXIDE: NO is one of the most important mediators of endothelial antiatherothrombotic functions. Loss of endothelial production, called "endothelial dysfunction", i.e. loss of endothelial vasorelaxing, antiaggregate and leukocyte antiadhesion properties, could lead to increased fatty streak formation and acute arterial events (thrombus formation, vascular spasm). ANIMAL EXPERIMENTS: Although animal models strongly suggest a major role for NO in the pathophysiology of atherosclerosis, human studies with nitrates have been disappointing to date. The local effect of NO is probably closely adapted to local conditions. Therefore, massive delivery of NO as is achieved with nitrates could not repair endothelial dysfunction.     

Implantable defibrillators. Sudden death: high risk

INCIDENCE: The incidence of sudden death remains high. The basic causes are related to ischemic heart disease and heart failure. Automatic defibrillation is the best treatment, as first conceived and implanted by Mirovski twenty years ago. MARKERS OF RISK OF SUDDEN DEATH: Left ventricular dysfunction, functional class and spontaneous and induced ventricular hyperexcitability identify a high-risk population. THERAPEUTIC APPROACH: Drug treatments used in the post infarction period or for heart failure (beta-blockers, converting enzyme inhibitors and amiodarone) have demonstrated a certain efficacy in preventing sudden death. However, different therapeutic trials comparing the efficacy of defibrillators and drug treatments have demonstrated the 20 to 46% superiority of defibrillation in terms of reduced mortality.     

Microangiopathy of the inner ear, retina, and brain (Susac syndrome): report of a case

Microangiopathy of the inner ear, retina, and brain was first described in 1979 by John O. Susac. Since then, approximately 60 cases have been reported. Otolaryngologists must be aware of this syndrome, in which cochleovestibular symptoms are an important part of the diagnosis. In this article, we report a new case of Susac syndrome and discuss the diagnosis, physiopathologic characteristics, and treatment of this disease.     

20-Year prevalence projections for dementia and impact of preventive policy about risk factors

Incidence of dementia increases sharply with age and, because of the increase in life expectancy, the number of dementia cases is expected to rise dramatically over time. Some studies suggest that controlling some modifiable risk factors for dementia like diabetes or hypertension could lower its incidence. However, as treating these vascular factors would also reduce mortality risk, the actual impact of such public-health intervention on dementia prevalence is not known. Accounting for the impact of dementia and risk factors on mortality, the aim of this work was (1) to compute projections of age- and-sex specific prevalence of dementia in France from 2010 to 2030, (2) to evaluate how public-health interventions targeting risk factors for dementia could change these projections. Age-and-sex specific incidence of dementia and mortality of demented subjects were estimated from the Paquid population-based cohort using a semi-parametric illness-death model. Future global mortality rates and population sizes were obtained from national demographic projections. Under the assumption that life expectancy will increase by 3.5 years for men and 2.8 years for women by 2030, the number of subjects with dementia was estimated to increase by about 75 % from 2010 to 2030 with a 200 % increase after 90 years of age. Therapeutic intervention on the whole population reducing high blood pressure prevalence would lead to a decrease in both dementia incidence rates and mortality and would have a modest impact on the number of dementia cases. On the other hand, a preventive dementia treatment targeting ApoE4 carriers would probably not improve survival and hence would decrease dementia prevalence by 15–25 %.     

Elbasvir and grazoprevir for chronic hepatitis C genotypes 1 and 4

Introduction: During the last few years, treatment of hepatitis C virus (HCV) revolutionized with the appearance of direct antiviral agents especially for patients with HCV genotypes 1 and 4 infections. Elbasvir (NS5A inhibitor) and grazoprevir (NS3/4A protease inhibitor) are newly developed drugs that are presented in fixed dose combination tablets.

Areas covered: This review covers the mechanism of action, pharmacokinetic and pharmacodynamics properties, clinical uses, safety and efficacy of elbasvir/grazoprevir in managing a wide variety of easy and difficult to treat populations (such as presence of cirrhosis, treatment experienced, co-infection with HIV and patients with inherited blood disorders).

Expert commentary: Elbasvir/grazoprevir combination showed great efficacy with high rates of sustained virological response rates in genotypes 1 and 4 HCV infection. In addition, it retained a good safety profile and is generally well tolerated.     

Spontaneous breakage of intracorneal ring segments (ICRS) 8 years after implantation

We present a case of spontaneous in situ breakage of intracorneal ring segments (ICRSs) 8?years after their implantation in a patient with keratoconus. The patient presented to our clinic with a red and painful right eye that had not improved despite topical steroids and antibiotics. The decision was made to explant the broken ICRSs from the cornea and send them for laboratory analyses, by which manufacturer defects were excluded. It is noteworthy that corneal curvature re-steepening was observed 4?months after ICRS removal despite the performance of crosslinking (CXL) 1?year prior to ICRS implantation.