Ability of novice clinicians to interpret high-resolution optical coherence tomography for ocular surface lesions

Objective

To assess the ability of novice clinicians to use a commercially available high-resolution anterior segment optical coherence tomography (HR-OCT) device to diagnose various lesions of the ocular surface and cornea.

Factors Associated with Occurrence of Radiation-induced Optic Neuropathy at “Safe” Radiation Dosage

Background: Radiation-induced optic neuropathy (RION) is a rare, and often visually devastating, complication of radiation therapy (RT) near the anterior visual pathways. Methods: A retrospective case series of patients who developed RION at a tertiary medical center, followed by a case-control study comparing RION cases with matched controls who received RT. Results: Thirteen patients (18 eyes) with RION were identified. Radiation modalities included external beam photon radiation, whole brain radiation, stereotactic radiosurgery, proton beam, and unknown. Most patients received doses below published “safe” thresholds (<55 Gy; <8–10 Gy for stereotactic radiosurgery). There was no statistically significant difference in prevalence of vasculopathic factors between cases and controls; on subgroup analysis in three patients who received surprisingly low radiation doses, smoking (p=0.05) and hypertension (p=0.02) appeared more prevalent. Conclusion: RION can occur at doses below published “safe” thresholds and with different RT modalities. Smoking and hypertension might be risk factors for RION.     

Metabolic crosstalk between fatty pancreas and fatty liver: effects on local inflammation and insulin secretion

Aims/hypothesis

Obesity-linked ectopic fat accumulation is associated with the development of type 2 diabetes. Whether pancreatic and liver steatosis impairs insulin secretion is controversial. We examined the crosstalk of human pancreatic fat cells with islets and the role of diabetogenic factors, i.e. palmitate and fetuin-A, a hepatokine released from fatty liver.

Methods

Human pancreatic resections were immunohistochemically stained for insulin, glucagon, somatostatin and the macrophage/monocyte marker CD68. Pancreatic adipocytes were identified by Oil Red O and adiponectin staining. Primary pancreatic pre-adipocytes and differentiated adipocytes were co-cultured with human islets isolated from organ donors and the metabolic crosstalk between fatty liver and fatty pancreas was mimicked by the addition of palmitate and fetuin-A. Insulin secretion was evaluated by ELISA and RIA. Cytokine expression and secretion were assessed by RT-PCR and multiplex assay, respectively. Subcellular distribution of proteins was examined by confocal microscopy and protein phosphorylation by western blotting.

Results

In human pancreatic parenchyma, highly differentiated adipocytes were detected in the proximity of islets with normal architecture and hormone distribution. Infiltration of adipocytes was associated with an increased number of CD68-positive cells within islets. In isolated primary pancreatic pre-adipocytes and differentiated adipocytes, palmitate and fetuin-A induced IL6, CXCL8 and CCL2 mRNA expression. Cytokine production was toll-like receptor 4 (TLR4)-dependent and further accentuated in pre-adipocytes when co-cultured with islets. In islets, IL6 and CXCL8 mRNA levels were also increased by fetuin-A and palmitate. Only in macrophages within the isolated islets, palmitate and fetuin-A stimulated the production of the cytotoxic cytokine IL-1β. Palmitate, but not fetuin-A, exerted pro-apoptotic effects in islet cells. Instead, fetuin-A impaired glucose-induced insulin secretion in a TLR4-independent, but c-Jun N-terminal kinase- and Ca²⁺-dependent, manner.

Conclusions/interpretation

These results provide the first evidence that fetuin-A-mediated metabolic crosstalk of fatty liver with islets may contribute to obesity-linked glucose blindness of beta cells, while fatty pancreas may exacerbate local inflammation.

     

Prevention of Arthritis Markers in Experimental Animal and Inflammation Signalling in Macrophage by Karanjin Isolated from Pongamia pinnata Seed Extract

Karanjin, the furanoflavonoid reported to possess gastroprotective and anti‐diabetic properties, was investigated against experimental arthritis and its molecular signalling in inflammation was explored in macrophages. Karanjin was isolated from hexane extract of Pongamia pinnata seeds and was evaluated on arthritis markers in adjuvant induced arthritis model (AIA) in two doses (per oral; 10 mg/kg/day and 20 mg/kg/day). Karanjin dose dependently reduced collagen and cartilage breakdown markers viz. urinary hydroxyproline and glucosamine, respectively, serum lysosomal enzymes responsible for articular cartilage damage, and major proinflammatory cytokine TNFα, secreted by macrophages involved in articular inflammation and destruction. Karanjin also prevented joint damage as evidenced from arthritis score, radiographic and histopathological analysis. To delineate the molecular target of Karanjin, in vitro study on LPS induced macrophages were performed at calibrated non toxic doses (4 µg/mL and 6 µg/mL). Karanjin reduced TNFα production and also showed potent inhibitory effect on nitric oxide and reactive oxygen species production which is generally induced by TNFα from activated macrophages. NF‐κB, the key regulator of TNFα signalling during inflammation was significantly suppressed by Karanjin. Our study for the first time highlights the anti‐inflammatory role of Karanjin in experimental arthritis model as well as on macrophage signalling, thereby depicting its probable mechanism of action. Copyright © 2014 John Wiley & Sons, Ltd.     

Predictors of mortality in children due to severe and very severe pneumonia

Background:

Mortality due to pneumonia in children is more than any other illness. Limited data is available to predict mortality in children with pneumonia from central India.

Aim:

To study predictors of mortality in children aged 1-59 months hospitalised with severe and very severe pneumonia.

Materials and Methods:

Present study was observational longitudinal study that was done in a tertiary care hospital of central India. Two hundred and ninety children, aged 1-59 months, presented with severe and very severe pneumonia were enrolled in this study. Outcome and predictors of mortality were studied. Data was analysed with Chi-square test, univariate and multivariate regression analysis.

Results:

Out of 270 enrolled study subjects, maximum (108, 37.24%) were belonged to 1-6-months age group. Proportion of mortality was maximum (16, 64.00%) in that age group. Overall case fatality rate was 8.62%. Among significant variables, delayed hospital referral [adjusted odds ratio (OR)-52.09, 95% confidence interval (CI)- 6.74-402.39], incomplete immunisation (OR-12.28, 95% CI-2.15-69.93), severe malnutrition (Z score < −3) (OR-15.51, 95% CI- 2.04-117.83), refusal to feed (OR- 30.57, 95% CI- 2.47-378.26), and hypoglycaemia (OR- 6.98, 95% CI- 1.05-46.30) were found significant independently on multivariate regression analysis. Conclusion: Delayed hospital referral, incomplete immunisation, severe malnutrition, refusal to feed, and hypoglycaemia were independent predictors of mortality in children with severe and very severe pneumonia.     

Diagnostic Challenge with Nocardia Subretinal Abscess: A Case Report from Tuberculosis-Endemic Region

Purpose: To describe a case of Nocardia subretinal abscess, which posed a diagnostic challenge due to the presence of mycobacterial genome in sample obtained from fine needle aspiration biopsy (FNAB).

Methods: A retrospective chart review.

Results: A 25-year-old male presented with sudden, painless onset diminution of vision of left eye and found to have placoid patch of choroiditis just temporal to the macula in right eye and showed vitritis, subretinal abscess with exudative retinal detachment and vitreous hemorrhage in left eye. Both aqueous and vitreous samples were negative microbiologically and polymerase chain reaction for various genomes. Sample obtained from FNAB was positive for mycobacterial genome and yielded Nocardia arthritidis on culture. She was treated with antitubercular therapy and intravenous and intravitreal antimicrobials.

Conclusions: Nocardia subretinal abscess can be a diagnostic challenge in tuberculosis-endemic region, especially in conditions when there is co-infection with Mycobacterium tuberculosis.     

Characterization of a neutralization-escape variant of SHIVKU-1, a virus that causes acquired immune deficiency syndrome in pig-tailed macaques

A chimeric simian-human immunodeficiency virus (SHIV-4) containing the tat, rev, vpu, and env genes of HIV type 1 (HIV-1) in a genetic background of SIVmac239 was used to develop an animal model in which a primate lentivirus expressing the HIV-1 envelope glycoprotein caused acquired immune deficiency syndrome (AIDS) in macaques. An SHIV-infected pig-tailed macaque that died from AIDS at 24 weeks postinoculation experienced two waves of viremia: one extending from weeks 2-8 and the second extending from week 18 until death. Virus (SHIVKU-1) isolated during the first wave was neutralized by antibodies appearing at the end of the first viremic phase, but the virus (SHIVKU-1b) isolated during the second viremic phase was not neutralized by these antibodies. Inoculation of SHIVKU-1b into 4 pig-tailed macaques resulted in severe CD4(+) T cell loss by 2 weeks postinoculation, and all 4 macaques died from AIDS at 23-34 weeks postinoculation. Because this virus had a neutralization-resistant phenotype, we sequenced the env gene and compared these sequences with those of the env gene of SHIVKU-1 and parental SHIV-4. With reference to SHIV-4, SHIVKU-1b had 18 and 6 consensus amino acid substitutions in the gp120 and gp41 regions of Env, respectively. These compared with 10 and 3 amino acid substitutions in the gp120 and gp41 regions of SHIVKU-1. Our data suggested that SHIVKU-1 and SHIVKU-1b probably evolved from a common ancestor but that SHIVKU-1b did not evolve from SHIVKU-1. A chimeric virus, SHIVKU-1bMC17, constructed with the consensus env from the SHIVKU-1b on a background of SHIV-4, confirmed that amino acid substitutions in Env were responsible for the neutralization-resistant phenotype. These results are consistent with the hypothesis that neutralizing antibodies induced by SHIVKU-1 in pig-tailed macaque resulted in the selection of a neutralization-resistant virus that was responsible for the second wave of viremia.     

A safer alternative approach to penetrating keratoplasty in opaque corneas

Background:This video demonstrates a useful technique of keratoplasty which can be routinely undertaken by all surgeons when imaging modalities such as anterior segment optical coherence tomography are not available and prior patient history is not forthcoming.Purpose:To demonstrate a technique of lamellar separation and layer by layer removal of host cornea when dealing with keratoplasty in perforated corneal ulcers, adherent leucomas, dense corneal opacities, which obscure visualization of the iris and anterior chamber details.Synopsis:In this video, we demonstrate penetrating keratoplasty in a failed opacified graft with iridocorneal adhesions, with no visualization of anterior chamber details. Lamellar dissection of the host cornea is done starting at its periphery and moving centrally, with gentle peeling of the superficial layers, the epithelium and bulk of stroma, following which, the deeper portion of the cornea is dissected and separated from underlying adherent iris tissue. Layer by layer separation allows better visualization through the remaining thin layers of the cornea. This permits fine dissection and layered removal of the cornea, thereby avoiding injury to iris and lens. Debulking of the host cornea decreases the force that is needed to be applied to separate adherent iris tissue from the host cornea, and reduces the chances of sudden entry into the anterior chamber and subsequent damage to the iris or lens. This also reduces the chance of iris tears, iridodialysis and bleeding from the iris and helps maintain iris integrity, which is essential intraoperatively for protection of lens and anterior chamber formation, and to avoid glare and photophobia postoperatively. Preventing iris damage also reduces the chances of formation of peripheral anterior synechiae (PAS), which can predispose to graft rejection, graft failure and secondary glaucoma.Highlights:Layer by layer corneal separation beginning inside the graft host junction, careful separation of iridocorneal adhesions and PAS is a helpful technique to optimally preserve the anterior segment anatomy during difficult cases of penetrating keratoplasty.Online Video Link: https://youtu.be/ZmQQhuOnAh4