Vogt-Koyanagi-Harada syndrome in a 10-year-old child

A 10-year-old female child attended outpatients department of Regional Institute of ophthalmology, Kolkata with the complaints of gradual dimness of vision of both eyes, recurrent pain, redness and photophobia. On examination, she was found to have bilateral anterior uveitis, poliosis and vitiligo. Laboratory tests were performed to rule out other causes of granulomatous uveitis. She was treated with topical and systemic steroids and topical cycloplegic. Then pars plana vitrectomy with lensectomy was carried out. The vision still remained poor.     

Systemic adverse effects and toxicities associated with immunotherapy: A review

Immunotherapy is rapidly evolving secondary to the advent of newer immunotherapeutic agents and increasing approval of the current agents by the United States Food and Drug Administration to treat a wide spectrum of cancers. Immunotherapeutic agents have gained immense popularity due to their tumor-specific action. Immunotherapy is slowly transforming into a separate therapeutic entity, and the fifth pillar of management for cancers alongside surgery, radiotherapy, chemotherapy, and targeted therapy. However, like any therapeutic entity it has its own adverse effects. With the increasing use of immuno-therapeutic agents, it is vital for physicians to acquaint themselves with these adverse effects. The aim of this review is to investigate the common systemic adverse effects and toxicities associated with the use of different classes of immunotherapeutic agents. We provide an overview of potential adverse effects and toxicities associated with different classes of immunotherapeutic agents organized by organ systems, as well as an extensive discussion of the current recommendations for treatment and clinical trial data. As we continue to see increasing usage of these agents in clinical practice, it is vital for physicians to familiarize themselves with these effects.     

Three Dimensional Transient Multifield Analysis of a Piezoelectric Micropump for Drug Delivery System for Treatment of Hemodynamic Dysfunctions

In this paper, we present design of a transdermal drug delivery system for treatment of cardiovascular or hemodynamic disorders such as hypertension. The system comprises of integrated control electronics and microelectromechanical system devices such as micropump, micro blood pressure sensor and microneedle array. The objective is to overcome the limitations of oral therapy such as variable absorption profile and the need for frequent dosing, by fabricating a safe, reliable and cost effective transdermal drug delivery system to dispense various pharmacological agents through the skin for treatment of hemodynamic dysfunction such as hypertension. Moreover, design optimization of a piezoelectrically actuated valveless micropump is presented for the drug delivery system. Because of the complexity in analysis of piezoelectric micropump, which involves structural and fluid field couplings in a complicated geometrical arrangement, finite element (FE) numerical simulation rather than an analytical system has been used. The behavior of the piezoelectric actuator with biocompatible polydimethylsiloxane membrane is first studied by conducting piezoelectric analysis. Then the performance of the valveless micropump is analyzed by building a three dimensional electric-solid-fluid model of the micropump. The effect of geometrical dimensions on micropump characteristics and efficiency of nozzle/diffuser elements of a valveless micropump is investigated in the transient analysis using multiple code coupling method. The deformation results of the membrane using multifield code coupling analysis are in good agreement with analytical as well as results of single code coupling analysis of a piezoelectric micropump. The analysis predicts that to enhance the performance of the micropump, diffuser geometrical dimensions such as diffuser length, diffuser neck width and diffuser angle need to be optimized. Micropump flow rate is not strongly affected at low excitation frequencies from 10 to 200 Hz. The excitation voltage is the more dominant factor that affects the flow rate of the micropump as compared with the excitation frequency. However, at extremely high excitation frequencies beyond 8,000 Hz, the flow rate drops as the membrane exhibits multiple bending peaks which is not desirable for fluid flow. Following the extensive numerical analysis, actual fabrication and performance characterization of the micropump is presented. The performance of the micropump is characterized in terms of piezoelectric actuator deflection and micropump flow rate at different operational parameters. The set of multifield simulations and experimental measurement of deflection and flow rate at varying voltage and excitation frequency is a significant advance in the study of the electric-solid-fluid coupled field effects as it allows transient, three dimensional piezoelectric and fluid analysis of the micropump thereby facilitating a more realistic multifield analysis. The results of the present study will also help to conduct relevant strength duration tests of integrated drug delivery device with micropump and microneedle array in future.     

A glycolytic phenotype is associated with prostate cancer progression and aggressiveness: a role for monocarboxylate transporters as metabolic targets for therapy

Metabolic adaptation is considered an emerging hallmark of cancer, whereby cancer cells exhibit high rates of glucose consumption with consequent lactate production. To ensure rapid efflux of lactate, most cancer cells express high levels of monocarboxylate transporters (MCTs), which therefore may constitute suitable therapeutic targets. The impact of MCT inhibition, along with the clinical impact of altered cellular metabolism during prostate cancer (PCa) initiation and progression, has not been described. Using a large cohort of human prostate tissues of different grades, in silico data, in vitro and ex vivo studies, we demonstrate the metabolic heterogeneity of PCa and its clinical relevance. We show an increased glycolytic phenotype in advanced stages of PCa and its correlation with poor prognosis. Finally, we present evidence supporting MCTs as suitable targets in PCa, affecting not only cancer cell proliferation and survival but also the expression of a number of hypoxia‐inducible factor target genes associated with poor prognosis. Herein, we suggest that patients with highly glycolytic tumours have poorer outcome, supporting the notion of targeting glycolytic tumour cells in prostate cancer through the use of MCT inhibitors. © 2015 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Characteristics of Internal Medicine Physicians Disciplined by Professional Colleges in Canada

Physician misconduct is of serious concern to patient safety and quality of care. Currently, there are limited data on disciplinary proceedings involving internal medicine (IM) physicians.The aim of this study was to investigate the number and nature of disciplinary cases among IM physicians compared with those of other disciplined physicians.Our retrospective study reviewed information from all provincial Colleges of Physicians and Surgeons (CPS) and compiled a database of all disciplined physicians from 2000 to 2013 in Canada. Disciplinary rate differences (RDs) were calculated for IM physicians and compared with other physicians.From 2000 to 2013, overall disciplinary rates were low (9.6 cases per 10,000 physician years). There were 899 disciplinary cases, 49 of which involved 45 different IM physicians. IM physicians comprised 10.8% of all disciplined physicians and were disciplined at a lower rate than non-IM physicians, incurring 5.18 fewer cases per 10,000 physician years than other physicians (95% confidence interval [CI] 3.62–6.73; P < 0.001). They were significantly less likely to be disciplined for: unprofessional conduct (RD 1.16; CI 0.45–1.87; P = 0.001); unlicensed activity (RD 0.78; CI 0.37–1.19; P < 0.001); standard of care issues (RD 1.37; CI 0.49–2.26; P = 0.002); sexual misconduct (RD 1.65; CI 0.90–2.40; P < 0.001); miscellaneous (RD 0.80; CI 0.11–1.50; P = 0.020); mental illness (RD 0.06; CI 0.01–0.12; P = 0.025); inappropriate prescribing (RD 0.74; CI 0.15–1.33; P = 0.010); and criminal conviction (RD 0.33; CI 0.00–0.65; P = 0.048). No significant differences were found with respect to unclear violations, fraudulent behavior/prevarication, or offenses involving drugs/alcohol (all RDs less than 0.32). IM physicians were also less likely to incur the following penalties: voluntary license surrender (RD 0.53; CI 0.37–0.69; P < 0.001); suspension (RD 2.39; CI 1.26–3.51; P < 0.001); retraining/assessment (RD 1.58; CI 0.77–2.39; P < 0.001); restriction (RD 1.60; CI 0.74–2.46; P < 0.001); other (RD 0.52; CI 0.07–0.97; P = 0.030); formal reprimand (RD 2.78; CI 1.77–3.79; P < 0.001); or fine (RD 3.28; CI 1.89–4.67; P < 0.001). No significant differences were found with respect to revocation or mandated counseling/rehabilitation (all RDs less than 0.46).Generally, disciplinary rates among physicians were low. Compared with other physicians, IM physicians have significantly lower disciplinary rates overall and are less likely to incur the majority of disciplinary offenses and penalties.     

A Comparative Study of the Beneficial Effects of Ipratropium and Beclomethasone against Insulin-Induced Tracheal Tissue Contraction in a Guinea Pig Model

Objective

To evaluate the acute effects of insulin on airway reactivity and the protective effects of beclomethasone and ipratropium against insulin-induced airway hyperresponsiveness on isolated tracheal smooth muscle in a guinea pig model.

Materials and Methods

The trachea of each guinea pig was excised; one end of the tracheal strip was attached to the hook of the oxygen tube of a tissue bath and the other end was connected to a research-grade isometric force displacement transducer. The effects of varying concentrations of insulin (10⁻⁷ to 10⁻³M) and insulin pretreated with a fixed concentration of beclomethasone (10⁻⁶M) and ipratropium (10⁻⁶M) on the isolated tracheal tissue were studied by constructing cumulative concentration-response curves. Changes in tracheal smooth muscle contractions were recorded on a 4-channel oscillograph.

Results

The means ± standard error of the mean of the maximum amplitude of contraction with increasing concentrations of insulin and of insulin pretreated with fixed concentrations of beclomethasone and ipratropium were 35 ± 1.13, 22 ± 1.15 and 27.8 ± 1.27 mm, respectively.

Conclusion

The data showed that beclomethasone inhibited the contractile response of insulin to a greater extent than ipratropium. Thus we suggest that inhalational insulin pretreated with beclomethasone may be more efficacious than with ipratropium for the amelioration of potential respiratory adverse effects such as bronchoconstriction.Key Words: Airway hyper-reactivity, Inhaled insulin, Beclomethasone, Ipratropium, Tracheal muscle