Genetic contributions to Parkinson's disease

Sporadic Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by the loss of midbrain dopamine neurons and Lewy body inclusions. It is thought to result from a complex interaction between multiple predisposing genes and environmental influences, although these interactions are still poorly understood. Several causative genes have been identified in different families. Mutations in two genes [α-synuclein and nuclear receptor-related 1 (Nurr1)] cause the same pathology, and a third locus on chromosome 2 also causes this pathology. Other familial PD mutations have identified genes involved in the ubiquitin–proteasome system [parkin and ubiquitin C-terminal hydroxylase L1 (UCHL1)], although such cases do not produce Lewy bodies. These studies highlight critical cellular proteins and mechanisms for dopamine neuron survival as disrupted in Parkinson's disease. Understanding the genetic variations impacting on dopamine neurons may illuminate other molecular mechanisms involved. Additional candidate genes involved in dopamine cell survival, dopamine synthesis, metabolism and function, energy supply, oxidative stress, and cellular detoxification have been indicated by transgenic animal models and/or screened in human populations with differing results. Genetic variation in genes known to produce different patterns and types of neurodegeneration that may impact on the function of dopamine neurons are also reviewed. These studies suggest that environment and genetic background are likely to have a significant influence on susceptibility to Parkinson's disease. The identification of multiple genes predisposing to Parkinson's disease will assist in determining the cellular pathway/s leading to the neurodegeneration observed in this disease.     

ERP evidence of impaired central nervous system function in virally suppressed HIV patients on antiretroviral therapy.

OBJECTIVE: To examine the effects of human immunodeficiency virus (HIV) on central nervous system (CNS) function in patients receiving antiretroviral therapy (ART) who have suppressed viral loads. METHODS: Event-related brain potentials (ERPs) were recorded from 15 virally suppressed HIV patients and 15 age-, sex-, and education-matched controls while they performed a 3-stimulus auditory oddball task. The amplitude and latency of the P3a, P3b, and early auditory components were examined in HIV patients and controls. RESULTS: Virally suppressed HIV patients on ART were more depressed than controls, as determined by the Beck Depression Inventory (BDI). After controlling for the effects of depression, HIV patients had smaller P2, P3a, and P3b amplitudes and longer P3a and P3b latency than control subjects. BDI scores correlated positively with N1 latency in HIV patients and negatively with P3b amplitude in all subjects. CONCLUSIONS: These electrophysiological results suggest that, even in the absence of detectable levels of HIV in the peripheral blood, viral replication persists in the CNS and continues to cause disease in HIV patients on ART.     

Pseudo-outbreak of Acinetobacter lwoffii infection in a tertiary care center in Thailand.

We describe a pseudo-outbreak of Acinetobacter lwoffii infection that was recognized early. The pseudo-outbreak involved 16 patients and occurred 3.5 months after the GNS-506 Vitek automated system was introduced in the microbiology laboratory. Prompt confirmation of incomplete use of the automated system's algorithm as the point source of the misidentified A. lwoffii clinical isolates averted a full outbreak investigation and excess use of infection control resources.     

Mitigation of hearing loss from semi-circular canal transection in pseudomonas otitis media with ciprofloxacin-dexamethasone irrigation.

HYPOTHESIS: Irrigation of the mastoid with a quinolone antibiotic-steroid solution may mitigate hearing loss caused by iatrogenic semicircular canal injury in the presence of Pseudomonas aeruginosa (PA) otitis media (OM). BACKGROUND: Studies have shown the cochlea to be more vulnerable to semicircular canal transection (SCT)-related hearing loss in the presence of PA OM. Prophylactic systemic antibiotics and steroids may decrease this hearing loss, but SCT is usually not planned. The aim of this study was to determine if irrigation with ciprofloxacin-dexamethasone (cipro-dex) could improve hearing outcomes following SCT in PA OM. METHODS: PA OM was induced in 28 animals. After three to five days, unilateral SCT was performed in each animal, with sham SCT on the contralateral ear. At surgery, half of the animals (n = 14) underwent irrigation of the both mastoid bullae with cipro-dex; the second group of animals (n = 14) underwent irrigation of the bullae with sterile saline. Auditory thresholds were obtained immediately prior to SCT and 7-10 days after SCT. RESULTS: SCT ears treated with cipro-dex showed a mean click threshold improvement of 4.6 dB from pre-transection to 7-10 days post-transection, whereas thresholds in the SCT ears treated with saline worsened by 7.5 dB (p = 0.15). CONCLUSION: Irrigation of the guinea pig bulla with cipro-dex following SCT in the setting of PA OM appears safe and may yield beneficial effects on hearing.     

Double-orifice mitral valve with intact atrioventricular septum: an echocardiographic study with anatomic and functional considerations.

We identified 18 patients with double-orifice mitral valve (DOMV) and intact atrioventricular (AV) septum out of 40,179 echocardiographic studies performed between 1997 and 2002 at Children's Hospital, Denver, CO. In this study we describe (1) the anatomic characteristics of the DOMV in the absence of AV septal defect, (2) the function of the mitral valve by spectral and color Doppler flow mapping, and (3) associated lesions. The topographic location of the orifices in the leaflets suggests possible embryologic mechanisms of DOMV. In this series, DOMV was most commonly associated with left-sided obstructive lesions (in 39% of patients). Spectral and color Doppler interrogation demonstrated a normal flow profile in most cases; only 2 patients had significant mitral regurgitation or stenosis. Therefore, due to the uncertain natural history of this lesion and the potential need for endocarditis prophylaxis, careful imaging of the mitral valve is recommended, particularly in the presence of left-sided obstructive lesions.     

PFT-α对结肠上皮细胞凋亡和周期的影响及机制探讨

目的探讨p53抑制剂（p-fifty three inhibitor—alpha，PFT-α）对结肠上皮细胞凋亡、周期的影响及机制。研究PFT-α对热化疗损伤结肠上皮细胞的影响。方法顺铂联合温热处理原代培养结肠七皮细胞30min，对比加入不同浓度PFT-α后，Annexin V—FITC／PI染色，流式细胞仪检测细胞凋亡。PI染色检测细胞周期。Western blot检测结肠上皮细胞Cyclin B1和Cdc2（Tyr15）表达。结果不同浓度PFT-α作用于热化疗处理的结肠上皮细胞后，细胞凋亡率下降且呈剂量依赖性。流式细胞仪细胞周期分析显示在运用PFT-α后，结肠上皮细胞的G2／M延长，CyclinB1和Cde2（Tyr15）蛋白表达随PFT—α的剂量升高而逐渐增强。结论PFT-α可能通过促进CyclinB1蛋白表达，Cde2（Tyr15）磷酸化水平升高，降低CyclinB1／Cde2活性，细胞停滞于G2／M期，减轻热化疗对结肠上皮细胞的损伤。     

Determinants of health-service use by low-income people.

Poverty influences health status, life expectancy, health behaviours, and use of health services. This study examined factors influencing the use of health-related services by people living in poverty. In the first phase, 199 impoverished users of health-related services in 2 large Canadian cities were interviewed by their peers. In the second phase, group interviews with people living in poverty (n = 52) were conducted. Data were analyzed using thematic content analysis. Diverse health-related services were used to meet basic and health needs, to maintain human contact, and to cope with life's challenges. Use of services depended on proximity, affordability, convenience, information, and providers' attitudes and behaviours. Use was impeded by inequities based on income status. To promote the health of people living in poverty, nurses and other health professionals can enhance the accessibility and quality of services, improve their interactions with people living in poverty, provide information about available programs, offer coordinated community-based services, collaborate with other sectors, and advocate for more equitable services and policies.