Opsoclonus-myoclonus syndrome following long-term use of cyclosporine

Background: Cyclosporine A (CsA) is a widely used immunosuppressive agent that may provoke unexpected neurologic complications. The mechanism is unclear and variable intervals have been reported between CsA administration and onset of the related side effects. Here, we describe a case of delayed-onset CsA neurotoxicity presenting as opsoclonus-myoclonus syndrome (OMS).

Case details: A 37-year-old woman with a two-week period of opsoclonus and upper extremity myoclonus was admitted to our hospital. The patient had been taking CsA for 17 years after receiving a kidney transplant. Further evaluation did not reveal any other abnormalities. Seven days after switching from CsA to tacrolimus, in the absence of additional immune-modulating therapy, her neurologic symptoms improved considerably.

Conclusion: This is the case of delayed, long-term complications of CsA presenting as OMS. Symptoms resolved by substituting CsA with another immunomodulating drug. The etiology of the neurologic complications may involve paradoxically-enhanced delayed-type hypersensitivity.     

MHI-148 Cyanine Dye Conjugated Chitosan Nanomicelle with NIR Light-Trigger Release Property as Cancer Targeting Theranostic Agent

Purpose

Paclitaxel (PTX) loaded hydrophobically modified glycol chitosan (HGC) micelle is biocompatible in nature, but it requires cancer targeting ability and stimuli release property for better efficiency. To improve tumor retention and drug release characteristic of HGC-PTX nanomicelles, we conjugated cancer targeting heptamethine dye, MHI-148, which acts as an optical imaging agent, targeting moiety and also trigger on-demand drug release on application of NIR 808 nm laser.

Procedures

The amine group of glycol chitosan modified with hydrophobic 5β-cholanic acid and the carboxyl group of MHI-148 were bonded by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide chemistry. Paclitaxel was loaded to MHI-HGC nanomicelle by an oil-in-water emulsion method, thereby forming MHI-HGC-PTX.

Results

Comparison of near infrared (NIR) dyes, MHI-148, and Flamma-774 conjugated to HGC showed higher accumulation for MHI-HGC in 4T1 tumor and 4T1 tumor spheroid. In vitro studies showed high accumulation of MHI-HGC-PTX in 4T1 and SCC7 cancer cell lines compared to NIH3T3 cell line. In vivo fluorescence imaging of the 4T1 and SCC7 tumor showed peak accumulation of MHI-HGC-PTX at day 1 and elimination from the body at day 6. MHI-HGC-PTX showed good photothermal heating ability (50.3 °C), even at a low concentration of 33 μg/ml in 1 W/cm² 808 nm laser at 1 min time point. Tumor reduction studies in BALB/c nude mice with SCC7 tumor showed marked reduction in MHI-HGC-PTX in the PTT group combined with photothermal therapy compared to MHI-HGC-PTX in the group without PTT.

Conclusion

MHI-HGC-PTX is a cancer theranostic agent with cancer targeting and optical imaging capability. Our studies also showed that it has cancer targeting property independent of tumor type and tumor reduction property by combined photothermal and chemotherapeutic effects.

     

Community-Based Review of Research Across Diverse Community Contexts: Key Characteristics,Critical Issues,and Future Directions

A growing number of community-based organizations and community–academic partnerships are implementing processes to determine whether and how health research is conducted in their communities. These community-based research review processes (CRPs) can provide individual and community-level ethics protections, enhance the cultural relevance of study designs and competence of researchers, build community and academic research capacity, and shape research agendas that benefit diverse communities.To better understand how they are organized and function, representatives of 9 CRPs from across the United States convened in 2012 for a working meeting.In this article, we articulated and analyzed the models presented, offered guidance to communities that seek to establish a CRP, and made recommendations for future research, practice, and policy.A growing number of community-based organizations and community–academic partnerships are implementing processes to determine whether and how health research is conducted in their communities.1–12 These community-based research review processes (CRPs) can provide individual- and community-level ethics protections, enhance the cultural relevance of study designs and competence of researchers, build community and academic research capacity, and help to set research agendas that benefit diverse communities. In 2009, with funding from the Greenwall Foundation, Community-Campus Partnerships for Health (CCPH) completed the first national study of CRPs in the United States.2,13The study identified 109 CRPs that mainly function through community–academic partnerships, community-based organizations, community health centers, and tribes, with 30 more in development. These CRPs were primarily formed to ensure that the involved communities are engaged in and directly benefit from research and are protected from its harms. Some are federally recognized institutional review boards (IRBs) that approve, monitor, and review research involving human participants. Others are advisory bodies. They all routinely examine issues that institution-based IRBs typically do not, such as community risks and benefits of the research and cultural appropriateness of the study design.2,13To better understand how CRPs are organized and function, CCPH, The Bronx Health Link, and the Albert Einstein College of Medicine convened representatives of 3 community IRBs, 5 community-based research review committees, and 1 university-based community research review committee in the United States for a working meeting in 2012 (see the box on page 1295). The meeting goals were to celebrate successes, identify promising practices, address challenges, and plan collaborations. The 9 participating CRPs were purposefully invited to reflect diversity in terms of geography, community served, organizational structure, and experience. Meeting proceedings described the CRPs in attendance and highlighted the emerging themes.1 In this article, we articulated and analyzed their diverse models, offered guidance to communities that seek to establish or strengthen a CRP, and outlined an agenda for future research, practice, funding, and policy.

Community-Based Research Review Processes Discussed in This Article

Risk factors for latent tuberculosis infection in children in South Korea

Objectives: In South Korea, latent tuberculosis infection (LTBI) screening is a critical strategy associated with efforts to reduce the incidence of tuberculosis (TB). Currently, only children with a known history of TB contact are considered as pediatric high-risk groups for LTBI, and consequently, LTBI screening is only provided to these children. However, to reduce the incidence of TB, the high-risk groups that undergo LTBI screening should be expanded. This study aimed to assess the risk factors for LTBI among children living in South Korea with no known history of TB contact for the identification of additional high-risk groups. We investigated the risk factors for LTBI among US visa applicant children, who undergo LTBI screening regardless of their TB contact history.

Methods: We obtained data on demographic characteristics, medical history, Bacillus Calmette–Guerin (BCG) vaccination history, and results of LTBI screening for children aged 2–14 years. A tuberculin skin test was used for the diagnosis of LTBI, and an induration of 10 mm or greater was used to define a positive test. Adjusted odds ratios and 95% confidence intervals were calculated to determine the association between clinical and demographic variables and LTBI.

Results: Of the 1,664 study participants, 91 (5.5%) had LTBI. The binary logistic regression analysis showed that children born in high TB burden foreign countries had the highest odds of LTBI when considering all the risk factors investigated. Increasing age, absence of BCG vaccination, and a previous diagnosis of asthma were also significant risk factors for LTBI.

Conclusion: These results indicate that children born in high TB burden foreign countries should be considered a high-risk group for LTBI in South Korea; the inclusion of these children in LTBI screening should be considered.