AUTOIMMUNE RETINOPATHY MIMICKING HERITABLE RETINAL DEGENERATION IN A PATIENT WITH COMMON VARIABLE IMMUNE DEFICIENCY.

PURPOSE: 1) To describe a case of autoimmune retinopathy mimicking heritable photoreceptor degeneration in a patient with common variable immune deficiency and 2) to investigate the humoral and cell-mediated branches of the immune system in this patient to better understand the mechanism of immune-mediated photoreceptor damage in this disease. METHODS: Retrospective chart review with evaluation of multimodal imaging, genotype analysis, and investigation of circulating autoantibodies and T-cell response to retinal antigens. RESULTS: A 40-year-old woman with bilateral, progressive vision loss was referred for evaluation of a possible inherited retinal degeneration. She was found to have asymmetric peripheral visual field constriction, cystoid macular edema, vitreous cells, and bone spicule-like pigmentary changes in both eyes. An extensive workup for underlying infectious or inflammatory causes was unrevealing, and molecular analysis for heritable retinal degeneration failed to identify a plausible disease-causing genotype. Screening for antiretinal antibodies showed the presence of multiple antiretinal antibodies, consistent with a diagnosis of autoimmune retinopathy. Immunologic workup demonstrated markedly decreased levels of serum IgA and IgG, consistent with common variable immune deficiency. T-cells isolated from the patient showed increased proliferation when stimulated with human retinal proteins, supporting a role for both cell- and humoral-mediated autoimmunity. Treatment with mycophenolate mofetil and intravenous immunoglobin therapy slowed the progression of disease and resulted in preservation of her central vision. CONCLUSION: Autoimmune retinopathy can be seen in common variable immune deficiency and has clinical findings similar to heritable photoreceptor degeneration. Both the humoral and cellular immune responses are involved in the pathophysiology. Immune modulatory therapy has stabilized the disease course in this patient and may play an important role in the management of autoimmune retinopathy.

Barriers and enablers to health service access amongst people with diabetes: An exploration of the perceptions of health care staff in regional Australia.

Healthcare staff are in a unique position of understanding client experiences, physiological impacts of client behaviour, the local healthcare system and the physical environment in which the services operate. Their perspectives may provide insights into the feasibility and effectiveness of existing models of diabetes care and suggestions for improvements to models of care (MoC). The objective of this qualitative study was to explore the experiences of healthcare staff delivering care for people with diabetes at the request of an existing healthcare service. Semi-structured interviews were conducted with 21 healthcare staff from three community health centres in one region of Victoria, Australia, in 2018. Interviews were audio-recorded and transcribed verbatim. Data were subject to qualitative content analysis and, subsequently, emerging themes were classified at individual, relationship, community and societal levels of the social-ecological model (SEM). Perceived barriers of access to health services using the current MoC included a lack of public transport, low socioeconomic status, job insecurity (resulting in an inability to take time away from work) and inflexible appointment times, all of which negatively impact diabetes management. Perceived enablers included having a co-located, multidisciplinary team, a holistic approach to diabetes management and motivation resulting from improvement in diabetes-related health outcomes. The findings indicate that there is potential to improve the service in this region by adopting a more integrated, team-focused and accessible MoC.

The ARMS2 A69S Polymorphism Is Associated with Delayed Rod-Mediated Dark Adaptation in Eyes at Risk for Incident Age-Related Macular Degeneration.

PURPOSE: To examine the association between sequence variants in genetic risk factors for age-related macular degeneration (AMD) and delayed rod-mediated dark adaptation (RMDA), the first functional biomarker for incident AMD, in older adults with normal macular health and early AMD. DESIGN: Cross-sectional. PARTICIPANTS: Adults 60 years of age or older showing normal macular health (defined as both eyes at step 1 on the Age-Related Eye Disease Study 9-step AMD classification system) and those with AMD in one or both eyes (defined as steps 2-9). METHODS: Single nucleotide polymorphisms were genotyped in the complement factor H (CFH) and ARMS2 genes using a Taqman assay. Rod-mediated dark adaptation was assessed in 1 eye after photobleach with targets centered at 5° on the inferior vertical meridian. Rate of dark adaptation was defined by rod intercept time (RIT), duration (in minutes) required for sensitivity to reach a criterion sensitivity level in the latter half of the second component of rod recovery. Associations between CFH and ARMS2 polymorphisms and RMDA were adjusted for age and smoking. MAIN OUTCOME MEASURE: Rod intercept time. RESULTS: The sample consisted of 543 participants having both genotype and RIT determination; 408 showed normal macular health and 135 demonstrated AMD, most having early AMD (124 of 135). For the combined sample, higher RIT (slower RMDA) was observed for both the A69S variant in ARMS2 and the Y402H variant in CFH (adjusted P = 0.0001 and P = 0.0023, respectively). For healthy participants, the A69S variant in ARMS2 was associated with higher RIT (adjusted P = 0.0011), whereas the Y402H variant in CFH was not (adjusted P = 0.2175). For AMD patients, the A69S variant of ARMS2 and the Y402H variant of CFH were associated with higher RIT (adjusted P = 0.0182 and P = 0.0222, respectively). Those with a larger number of high-risk ARMS2 and CFH alleles showed higher RIT, in both healthy and AMD groups (adjusted P = 0.0002 and P < 0.0001, respectively). CONCLUSIONS: We report a novel association wherein older adults with high-risk ARMS2 and CFH genotypes are more likely to demonstrate delayed RMDA, the first functional biomarker for incident early AMD. Before the AMD clinical phenotype is present, those showing normal macular health with the ARMS2 A69S allele demonstrate delayed RMDA. Understanding ARMS2 function is a research priority.

Expanded Retinal Disease Spectrum Associated With Autosomal Recessive Mutations in GUCY2D.

PURPOSE: GUCY2D has been associated with autosomal recessive Leber congenital amaurosis and autosomal dominant cone-rod dystrophy. This report expands the phenotype of autosomal recessive mutations to congenital night blindness, which may slowly progress to mild retinitis pigmentosa. DESIGN: Retrospective case series. METHODS: Multicenter study of 5 patients (3 male, 2 female). RESULTS: All patients presented with night blindness since childhood. Age at referral was 9-45 years. Length of follow-up was 1-7 years. Best-corrected visual acuity at presentation ranged from 20/15 to 20/30 and at most recent visit averaged 20/25. No patient had nystagmus or high refractive error. ISCEV standard electroretinography revealed nondetectable dark-adapted dim flash responses and reduced amplitude but not electronegative dark-adapted bright flash responses with similar waveforms to the reduced-amplitude light-adapted single flash responses. The 30 Hz flicker responses were relatively preserved. Macular optical coherence tomography revealed normal lamination in 3 patients, with abnormalities in 2. Goldmann visual fields were normal at presentation in children but constricted in 1 adult. One child showed loss of midperipheral fields over time. Fundus appearance was normal in childhood; the adult had sparse bone spicule-like pigmentation. Full-field stimulus testing (FST) revealed markedly decreased retinal sensitivity to light. Dark adaptation demonstrated lack of rod-cone break. Two patients had tritanopia. All 5 had compound heterozygous mutations in GUCY2D. Three of the 5 patients harbor the Arg768Trp mutation reported in GUCY2D-associated Leber congenital amaurosis. CONCLUSIONS: Autosomal recessive GUCY2D mutations may cause congenital night blindness with normal acuity and refraction, and unique electroretinography. Progression to mild retinitis pigmentosa may occur.

Treatment of cervical dysplasia with the Fischer cone biopsy excisor in a family medicine office: a case series.

PURPOSE: The purpose of this study was to evaluate the use of the Fischer cone biopsy excisor (FCBE) as the primary electrode for treatment of cervical dysplasia in a family medicine office. METHODS: Retrospective analysis of cervical electrosurgical excision procedures in patients with cervical intraepithelial neoplasia (CIN) performed in our Family Medicine Center between 2002 and 2005. RESULTS: We reviewed 91 cases. Indication for excision was >or=CIN II in 86.8% of the patients. In the FCBE group (n = 86), 95% of the specimen margins were negative for dysplasia, 90% had no reported thermal artifact, and 81% were submitted unfragmented. In the FCBE and the loop electrosurgical excision procedure (LEEP) group (n = 5), 4 of the 5 specimens' margins were negative for dysplasia. Reported complications included palpitations or flushing during cervical block (32%), pain (9%), and heavy bleeding (3%). CONCLUSION: In this case series the use of the FCBE with or without the LEEP in a family medicine office provided a high rate of negative margins for dysplasia and a low rate of fragmentation and thermal artifact. Family physicians who perform LEEP can also use the FCBE safely in their offices to treat cervical dysplasia.

A conducting-polymer platform with biodegradable fibers for stimulation and guidance of axonal growth.

A biosynthetic platform composed of a conducting polypyrrole sheet embedded with unidirectional biodegradable polymer fibers is described (see image; scale bar = 50 µm). Such hybrid systems can promote rapid directional nerve growth for neuro-regenerative scaffolds and act as interfaces between the electronic circuitry of medical bionic devices and the nervous system.

Nerve repair: a conducting-polymer platform with biodegradable fibers for stimulation and guidance of axonal growth (adv. Mater. 43/2009).

Effective functional innervation of medical bionic devices, as well as re-innervation of target tissue in nerve and spinal cord injuries, requires a platform that can stimulate and orientate neural growth. Gordon Wallace and co-workers report on p. 4393 that conducting and nonconducting biodegradable polymers show excellent potential as suitable hybrid substrata for neural regeneration and may form the basis of electrically active conduits designed to accelerate nerve repair.

Anaplasma phagocytophilum AnkA is tyrosine-phosphorylated at EPIYA motifs and recruits SHP-1 during early infection.

Anaplasma phagocytophilum is an intracellular pathogen that infects and survives in neutrophilic granulocytes. The A. phagocytophilum genome encodes a type four secretion system (T4SS) that may facilitate intracellular survival by translocation of virulence factors, but to date, no such factors have been identified. Because T4SS-translocated proteins of several intracellular organisms undergo tyrosine phosphorylation by host cell kinases, we investigated tyrosine phosphorylation of A. phagocytophilum proteins during infection. Within minutes after incubation of A. phagocytophilum with HL-60 cells or PMN, a 190 kDa bacterial protein, AnkA, was increasingly tyrosine-phosphorylated. A. phagocytophilum binding to host cells without entry was sufficient for AnkA tyrosine phosphorylation. An in vitro Src kinase assay demonstrated that purified AnkA expressed in Escherichia coli was phosphorylated at tyrosines located at the C-terminal portion of AnkA. Similarly, AnkA expressed in COS-7 cells underwent tyrosine phosphorylation by Src at the C-terminus. The phosphorylated tyrosines were located in EPIYA motifs that display the consensus sequence for binding to SH2 domains. Immunoprecipitation studies demonstrated AnkA binding to the host cell phosphatase SHP-1 during early infection. Phosphorylation of the EPIYA motifs and the presence of the SH2 domains were necessary for AnkA-SHP-1 interaction. We conclude that AnkA is a translocated virulence factor that is tyrosine-phosphorylated by host cell kinases upon translocation into the host cell early during infection. A. phagocytophilum may manipulate the host cell through SHP-1 recruitment.

Health status among emergency department patients approximately one year after consecutive disasters in New York City.

OBJECTIVES: Emergency department (ED) patients with disaster-related experiences may present with vague symptoms not clearly linked to the event. In 2001, two disasters in New York City, the World Trade Center disaster (WTCD) and the subsequent American Airlines Flight 587 crash, presented an opportunity to study long-term consequences of cumulative disaster exposure (CDE) on health-related quality of life (HRQOL) among ED patients. METHODS: From July 15 to October 30, 2002, a systematic sample of stable, adult patients from two EDs in New York City were enrolled. Participants completed a self-administered questionnaire. The Short Form 36 (SF-36) was used to assess overall health status. Bivariate analyses were conducted to identify individual correlates of worsening health status. Multivariate regression was performed to identify the association between various factors and overall health status, while controlling for relevant sociodemographic variables. RESULTS: Four hundred seventy-one patients (54.6% female) participated. The participation rate was 73.4%. One hundred sixty-one participants (36%) reported direct, indirect, or occupational exposure to the WTCD; 55 (13.3%) had direct, indirect, or occupational exposure to the plane crash; 33 (8.1%) had both exposures. In separate multivariate models, CDE predicted lower SF-36 scores for general health (p < 0.0096), mental health (p < 0.0033), and bodily pain (p < 0.0046). CONCLUSIONS: In the year following mass traumatic events, persons with CDE had lower overall health status than those with one or no disaster exposure. Clinicians should consider the impact that traumatic events have on the overall health status of ED patients in the wake of consecutive disasters.