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- Phase II drugs under investigation for allergic conjunctivitis. [JOURNAL ARTICLE]
- Expert Opin Investig Drugs 2014 Jul 25.:1-16.
Introduction: Ocular allergies comprise a spectrum of conditions that are underreported and underdiagnosed, and are frequently associated with rhinoconjunctivitis. Although allergic conjunctivitis is often not a sight-threatening condition, it could have a significant impact on a person's quality of life, morbidity and productivity. A variety of agents are available for the treatment of allergic conjunctivitis, including antihistamines, mast-cell stabilizers, dual action agents, glucocorticoids, calcineurin inhibitors and immunotherapy. Areas covered: The goal of this review is to investigate new therapeutic strategies for the treatment of ocular allergy. Within, the authors analyze the pharmacological management of allergic conjunctivitis and highlight Phase II clinical trial studies. Expert opinion: Recent findings about the pathophysiology of allergic conjunctivitis have enabled us to gain a better understanding of the molecular and cellular mechanisms of ocular disease. This, in turn, has led to the identification of novel targets, which, in turn, has led to the development of new therapeutic agents that are currently under evaluation in the first phases of clinical development. The most interesting agents, under development, are the new topical glucocorticoids, leukotriene receptor antagonists, resolvins, interleukin-1 receptor antagonists and integrin antagonists. The authors now await promising results, which can confirm the therapeutic value of these novel emerging drugs for treating allergic conjunctivitis.
- Conjunctival epithelial and goblet cell function in chronic inflammation and ocular allergic inflammation. [JOURNAL ARTICLE]
- Curr Opin Allergy Clin Immunol 2014 Jul 24.
Although conjunctival goblet cells are a major cell type in ocular mucosa, their responses during ocular allergy are largely unexplored. This review summarizes the recent findings that provide key insights into the mechanisms by which their function and survival are altered during chronic inflammatory responses, including ocular allergy.Conjunctiva represents a major component of the ocular mucosa that harbors specialized lymphoid tissue. Exposure of mucin-secreting goblet cells to allergic and inflammatory mediators released by the local innate and adaptive immune cells modulates proliferation, secretory function, and cell survival. Allergic mediators like histamine, leukotrienes, and prostaglandins directly stimulate goblet cell mucin secretion and consistently increase goblet cell proliferation. Goblet cell mucin secretion is also detectable in a murine model of allergic conjunctivitis. Additionally, primary goblet cell cultures allow evaluation of various inflammatory cytokines with respect to changes in goblet cell mucin secretion, proliferation, and apoptosis. These findings in combination with the preclinical mouse models help understand the goblet cell responses and their modulation during chronic inflammatory diseases, including ocular allergy.Recent findings related to conjunctival goblet cells provide the basis for novel therapeutic approaches, involving modulation of goblet cell mucin production, to improve treatment of ocular allergies.
- Diverse Wild Bird Host Range of Mycoplasma gallisepticum in Eastern North America. [Journal Article]
- PLoS One 2014; 9(7):e103553.
Emerging infectious diseases often result from pathogens jumping to novel hosts. Identifying possibilities and constraints on host transfer is therefore an important facet of research in disease ecology. Host transfers can be studied for the bacterium Mycoplasma gallisepticum, predominantly a pathogen of poultry until its 1994 appearance and subsequent epidemic spread in a wild songbird, the house finch Haemorhous mexicanus and some other wild birds. We screened a broad range of potential host species for evidence of infection by M. gallisepticum in order to answer 3 questions: (1) is there a host phylogenetic constraint on the likelihood of host infection (house finches compared to other bird species); (2) does opportunity for close proximity (visiting bird feeders) increase the likelihood of a potential host being infected; and (3) is there seasonal variation in opportunity for host jumping (winter resident versus summer resident species). We tested for pathogen exposure both by using PCR to test for the presence of M. gallisepticum DNA and by rapid plate agglutination to test for the presence of antibodies. We examined 1,941 individual birds of 53 species from 19 avian families. In 27 species (15 families) there was evidence for exposure with M. gallisepticum although conjunctivitis was very rare in non-finches. There was no difference in detection rate between summer and winter residents, nor between feeder birds and species that do not come to feeders. Evidence of M. gallisepticum infection was found in all species for which at least 20 individuals had been sampled. Combining the present results with those of previous studies shows that a diverse range of wild bird species may carry or have been exposed to M. gallisepticum in the USA as well as in Europe and Asia.
- A novel complex recombinant form of type 48-related human adenovirus species d isolated in Japan. [Journal Article]
- Jpn J Infect Dis 2014; 67(4):282-7.
Recently, new genotypes of human adenoviruses (HAdVs) have been reported and many of them have been found to be recombinant forms of different known types of HAdV species D (HAdV-D). The objective of this study was to document the evolutionary features of a novel isolate (HAdV_Chiba_E086/2012) obtained from the eye swab of a patient with conjunctivitis in Japan. Viral DNA was extracted from the isolate to sequence the whole genome by the Sanger method and aligned with available genome sequences of HAdV-Ds. The phylogenetic trees of the nucleotide sequences of the penton base, hexon, and fiber genes and the E3 region showed that HAdV_Chiba_E086/2012 is closest to HAdV genotype 65 (HAdV-GT65), HAdV-48, HAdV-GT60 and HAdV-22 at 98%, 99%, 95% and 98% identity, respectively, suggesting that this isolate is a novel recombinant form to be designated as P65H48F60. Further phylogenetic and recombination analyses of the genome alignment of the new isolate implied that nested recombination events involving HAdV-GT59, GT65, 48, GT60, 22, and some ancestral lineages or their close relatives have shaped its genome. These results showed that HAdV_Chiba_E086/2012 is the first HAdV-48-related HAdV found in Japan, which has the most complicated evolutionary history among the known HAdVs so far.
- Orbital complications in children: differential diagnosis of a challenging disease. [JOURNAL ARTICLE]
- Eur Arch Otorhinolaryngol 2014 Jul 24.
Orbital swelling in children presents diagnostic and therapeutic challenges. Most are associated with acute sinusitis with complicating factors possibly including: amaurosis, meningitis, intracranial abscess or even cavernous sinus thrombosis. However not all acute orbital swelling is associated with acute sinusitis. A careful evaluation is critical prior to initiating therapy. Clinical records of 49 children (27 girls, 22 boys, with an average age of 11.8 years) were retrospectively reviewed. Historical data evaluated included all available information from parents and previous treating physicians. All patients underwent intensive pediatric, ophthalmologic, and otorhinolaryngologic examinations. Computed tomography (CT scans) were additionally performed in 40 % of children. The results of any examinations were also evaluated. Eighteen of the 49 patients had an orbital complication due to acute sinusitis. All 18 had elevated body temperature, C-Reactive Protein (CRP) values and white blood cell counts. Endoscopy of the nose revealed pus in the middle meatus in each case. According to Chandlers' classification, ten children presented with a preseptal, and eight children had a postseptal orbital cellulitis. All patients were admitted to the hospital and treated with intravenous antibiotics. CT scans further demonstrated signs of subperiostal abscess in four children. Functional endoscopic sinus surgery (FESS) was required in six children, including all patients with subperiostal abscess. Twenty children experienced orbital swelling unrelated to acute sinusitis, i.e. atheroma, inflammed insect stings, dental related abscess, conjunctivitis, and Herpes simplex associated superinfection. In three children, acute orbital swelling was caused by an orbital tumor. Orbital complications of an acute sinusitis occur often in the pediatric patient group, and most of these patients can be treated conservative with intravenous antibiotics. Indications for FESS include failure to improve or worsening of clinical symptoms during 24 h of therapy, signs for subperiostal abscess in CT scan, and/or vision loss. Patients with infectous orbital complications had fever, elevated CRP and white blood cell counts. This symptom complex is key in making the correct diagnosis. Interestingly, 61 % of patients in this study demonstrated non-sinusitis related diseases leading to acute orbital swelling, which also required prompt recognition and appropriate therapy.
- Topical immunomodulators in the management of allergic eye diseases. [JOURNAL ARTICLE]
- Curr Opin Allergy Clin Immunol 2014 Jul 21.
Allergic eye diseases comprise a spectrum of diseases, with each condition being characterized by a complex immunopathology. The more severe and chronic conditions, such as vernal keratoconjunctivitis and atopic keratoconjunctivitis, involve predominantly mast cells and eosinophils, while also being associated with a preponderance of T cells. Treatment with topical antihistamines or mast cell stabilizers is often unsatisfactory, and therapy depends on topical corticosteroids. Corticosteroids have significant side-effects with long-term use; therefore, they appear to be more appropriate for short-term pulse therapy. Immunomodulatory agents can also be used to inhibit T-cell activation and show encouraging results among patients with severe allergic eye conditions. The present review is an attempt to present a coherent picture of the recent investigations of topical immunomodulatory agents' therapy in severe allergic eye diseases, especially cyclosporine A and tacrolimus, and their mechanisms of action.Immunomodulatory agents are commonly indicated for the treatment of severe and prolonged allergic conjunctivitis. This article reviews the recent studies of these drugs and the development of immunomodulatory treatments for severe allergic eye diseases.Cyclosporine A and tacrolimus are currently available for the treatment of severe allergic conjunctivitis. These agents have led to improved therapeutic results for patients with severe and chronic allergic eye diseases.
- Pharmaceutical approval update. [Journal Article]
- P T 2014 Jun; 39(6):415-23.
Apremilast (Otezla) for active psoriatic arthritis, omalizumab (Xolair) for chronic idiopathic urticaria, and grass pollen allergen extract (Oralair) for grass pollen-induced allergic rhinitis with or without conjunctivitis.
- High dose anakinra for treatment of severe neonatal Kawasaki disease: a case report. [Journal Article]
- Pediatr Rheumatol Online J 2014.:26.
We report an 11-week-old female who presented with Kawasaki disease (KD) complicated by macrophage activation syndrome (MAS). The infant presented to the hospital with persistent fever, cough, diarrhea, and emesis, among other symptoms. Her condition quickly began to decompensate, and she developed classic features (conjunctivitis, rash, cracked lips, distal extremity edema) prompting a diagnosis of acute KD. The patient was treated with standard therapy for KD including three doses of intravenous immunoglobulin (IVIG), aspirin, and high dose glucocorticoids with no change in her condition. Due to a high suspicion for MAS, high dose anakinra therapy was initiated resulting in dramatic clinical improvements. She also received one dose of infliximab for concern for coronary artery changes, and over the course of several months, anakinra and high dose glucocorticoids were tapered. Nearly complete reversal of echocardiogram changes were observed after 8 months, and the infant is now off all immunosuppressive therapy. In this case report, we briefly review the importance of early recognition of MAS in pediatric patient populations with rheumatic diseases, and we suggest early initiation of anakinra therapy as a rapid and effective treatment option.
- Evaluation of the impact of persistent subepithelial corneal infiltrations on the visual performance and corneal optical quality after epidemic keratoconjunctivitis. [JOURNAL ARTICLE]
- Acta Ophthalmol 2014 Jul 6.
Aim was to measure the effect of persistent subepithelial corneal infiltrates (SEIs) after epidemic keratoconjunctivitis (EKC) on visual performance and corneal optical quality.We examined 53 patients divided into two groups. Patients with previous EKC constituted the study group (Group 1, n: 27). Healthy age matched subjects constituted the control group (Group 2, n: 26). Study group was subdivided into eyes with SEI (Group 1A, 40 eyes) and healthy fellow eyes (Group 1B, 14 eyes). Patients were submitted to a complete examination including high- and low-contrast visual acuities (HCVA, LCVA), corneal topography and aberrometry.The mean interval between epidemic conjunctivitis and examination was 7.25 ± 5.63 months. Mean number of corneal infiltrates was 17.30 ± 14.38. The mean HCVA and LCVA were significantly lower in the eyes with SEI than fellow eyes and control group (p = 0.001). LCVA value was also worse in the fellow eyes when compared to control (p = 0.048). Corneal topography values were significantly higher in the eyes with SEI from both fellow eyes and control group. During corneal aberrometry, the mean root mean square value of spheric aberration, irregular astigmatism and total aberration were significantly higher in SEI group when compared to fellow eyes and control group (p < 0.05). Total aberrations were higher than control subjects in the fellow eyes. Trefoil aberration was higher in SEI group only when compared to control subjects, while there was no significant difference in coma aberration values between the groups (p > 0.05).Results of this study suggested that visual performance is compromised in patients with EKC by aberrations and changes in topographic variables.
- Ocular infections in sub-Saharan Africa in the context of high HIV prevalence. [JOURNAL ARTICLE]
- Trop Med Int Health 2014 Jul 7.
Healthy eyes and good vision are important determinants of populations' health across the globe. Sub-Saharan Africa is affected by simultaneous epidemics of ocular infections and human immunodeficiency virus (HIV). Ocular infection and its complications, along with cataract and ocular trauma, are common conditions in this region with great impact on daily life. In this review, we discuss the epidemiology, clinical manifestations and microbial aetiology of the most important infectious ocular conditions in sub-Saharan Africa: conjunctivitis, keratitis and uveitis. We focus specifically on the potential association of these infections with HIV infection, including immune recovery uveitis. Finally, challenges and opportunities for clinical management are discussed, and recommendations made to improve care in this neglected but very important clinical field.