Relevance of IgE,allergy and eye rubbing in the pathogenesis and management of Keratoconus

Keratoconus (KC) is an ectatic disease of the cornea characterized by localized thinning and protrusion causing irregular astigmatism, which can lead to significant visual impairment. KC has often been associated with allergy and/or atopy, which are immune-mediated inflammatory reactions primarily driven by IgE. A higher proportion of KC patients were reported to have history or suffer from systemic and/or ocular allergy with elevated allergen-specific IgE and/or total serum IgE. Eye rubbing, one of the risk factors for worsening of the disease and developing related complications in KC, is associated with IgE driven conditions. The current review enumerates and contextualizes the evidence related to IgE in mediating KC pathogenesis, including aberrant extra-cellular matrix remodeling. This review also discusses clinical strategies directed at modulating IgE-mediated responses in the management of KC, and the emerging academic and plausible clinical relevance of assessing serum and tear IgE (allergen-specific and total) status in improving the understanding of disease pathobiology, treatment planning, and prognosis.     

Pompe disease: An Indian series diagnosed on muscle biopsy by ultrastructural characterization

Pompe disease (PD) is a lysosomal storage disorder characterized by glycogen accumulation in muscle, with infantile-onset (IOPD) and late-onset (LOPD) types. Nineteen cases of PD were diagnosed over a 14-year period on muscle biopsy by ultrastructural examination. Pools of glycogen (intralysosomal and cytoplasmic) and excessive phagocytosis were seen in myofibers on electron microscopy. Glycogen was noted in endothelial cells in IOPD. Although PD accounts for a small fraction of muscle diseases, timely accurate diagnosis is imperative as it is treatable. Ultrastructural examination is necessary to confirm the diagnosis in cases with non-diagnostic light microscopic features, especially in adult LOPD patients.     

Chronic lymphocytic leukemia FISH panel: impact on diagnosis

Interphase fluorescence in situ hybridization (FISH) is an alternative to conventional chromosome analysis of chronic lymphocytic leukemia (CLL) cells. We analyzed 172 samples from 136 possible CLL cases using a FISH panel. Reflex testing with probes to CCND1, BCL2, BCL3, BCL11A, c-MYC, MALT1, and a break-apart immunoglobulin heavy chain (IGH) probe was done if more than 2 signals for 14q32 occurred. For 111 cases, there were sufficient data for analysis. Of 111 cases, 81 (72.9%) had 1 or more genetic abnormalities. The most frequent abnormality was 13q-, followed by trisomy 12, 11q-, and 17p-. In 13 cases, there were IGH abnormalities. Two cases with CCND1/IGH fusion were reclassified as mantle cell lymphoma. Four CLL cases had IGH fusion with BCL2, BCL3 (2 cases), and BCL11A; no fusion partner was detected in 7 cases. Morphologic features were atypical for CLL in 2 cases with IGH fusion (BCL11A and BCL3). The FISH CLL panel is useful to identify prognostic aberrations and to clarify diagnosis in cases with unusual morphologic features.     

Cerebral oxygenation declines at exercise intensities above the respiratory compensation threshold

During incremental exercise PaCO2 and PETCO2 begin to decline at the respiratory compensation threshold (RCT-GEX). Since PaCO2 alters cerebral blood flow it was hypothesized that there would be a systematic decline in cerebral oxygenation (Cox) measured by near infrared spectroscopy above the RCT (RCT-NIRS). Cardiorespiratory and NIRS responses were simultaneously monitored from the left frontal lobe during incremental exercise in 17 men. All subjects showed a decline in Cox above the RCT-GEX with a 20-40 s delay. Significant differences (P<0.01) were observed between the RCT-GEX and RCT-NIRS for time (9.83 versus 10.39 min), power (198 versus 212 W) and oxygen uptake (2.31 versus 2.43 L min-1). Intra-class correlations for power and absolute VO2 were 0.97 and 0.98, respectively. Bland-Altman analysis revealed no outliers for any of the variables. The results suggested that the decrease in Cox observed above the RCT was most likely due to a reduction in cerebral blood flow mediated by a decline in PaCO2. This decline in Cox could reduce neuronal activation thereby limiting maximal exercise capacity in healthy subjects.     

Upregulation of insulin receptor substrate-2 in pancreatic beta cells prevents diabetes

The insulin receptor substrate-2 (Irs2) branch of the insulin/IGF signaling system coordinates peripheral insulin action and pancreatic beta cell function, so mice lacking Irs2 display similarities to humans with type 2 diabetes. Here we show that beta cell-specific expression of Irs2 at a low or a high level delivered a graded physiologic response that promoted beta cell growth, survival, and insulin secretion that prevented diabetes in Irs2-/- mice, obese mice, and streptozotocin-treated mice; and that upon transplantation, the transgenic islets cured diabetes more effectively than WT islets. Thus, pharmacological approaches that promote Irs2 expression in beta cells, especially specific cAMP agonists, could be rational treatments for beta cell failure and diabetes.     

Plication for Severe Peyronie's Deformities Has Similar Long-Term Outcomes to Milder Cases

Introduction

Penile plication (PP) for Peyronie's disease (PD) is an established treatment option for mild to moderate curvature, but scant data exist regarding its utility in severe deformities.

The role of the IL-33/IL-1RL1 axis in mast cell and basophil activation in allergic disorders

Interleukin-33 (IL-33) is a recently discovered cytokine that belongs to the IL-1 superfamily and acts as an important regulator in several allergic disorders. It is considered to function as an alarmin, or danger cytokine, that is released upon structural cell damage. IL-33 activates several immune cells, including Th2 cells, mast cells and basophils, following its interaction with a cell surface heterodimer consisting of an IL-1 receptor-related protein ST2 (IL-1RL1) and IL-1 receptor accessory protein (IL-1RAcP). This activation leads to the production of a variety of Th2-like cytokines that mediate allergic-type immune responses. Thus, IL-33 appears to be a double-edged sword because, in addition to its important contribution to host defence, it exacerbates allergic responses, such as allergic rhinitis and asthma. A major purported mechanism of IL-33 in allergy is the activation of mast cells to produce a variety of pro-inflammatory cytokines and chemokines. In this review, we summarize the current knowledge regarding the genetics and physiology of IL-33 and IL-1RL1 and its association with different allergic diseases by focusing on its effects on mast cells and basophils.     

Prognostic factors for successful vaginal birth after cesarean section — Analysis of 162 cases

Objective

To analyze the success rate of VBAC (Vaginal birth after cesarean section) with reference to various factors and derive simple and easily usable prognostic factors to predict successful VBAC.

Methods (Study Design)

In this retrospective observational study, 162 women who had undergone successful trial of labor were analyzed to study the factors which contributed to successful trial of labor over a study period of one year. Maternal age, prior antenatal visits, prior obstetric history, neonatal weight and interconceptional period were studied with reference to outcome of VBAC. Success of VBAC when compared with prior indication for CS was studied. The role of instrumental deliveries for VBAC was analyzed. Maternal and perinatal mortality and morbidity were assessed. Chi square test was used to analyze the significance of each factor.

Results

Success rate of VBAC was 75%. Maternal age, prior antenatal care, prior vaginal delivery, neonatal weight and interconceptional period were all statistically significant predictors (P<0.001) of successful VBAC. Instrumental deliveries were helpful in successful VBAC and can be used prophylactically to cut short second stage. VBAC had no adverse maternal or perinatal outcome.

Conclusion

VBAC can be successfully tried in all women with prior cesarean section by careful selection and employing simple predictive factors.