IgG4- Related Disease as a Rare Cause of Tubulointerstitial Nephritis

Isolated IgG4 tubulointerstitial nephritis (TIN) is a rare disorder characterized by raised serum IgG4 levels and histological findings of dense lymphoplasmacytic infiltrates rich in IgG4 positive plasma cells. We report a case of isolated IgG4 TIN that presented with acute kidney injury in an 84 year old man with a polyclonal increase in his total IgG and a raised IgE of 381 kUA/L but without evidence of systemic autoimmunity. We draw a parallel with IgG4-related autoimmune pancreatitis and show raised levels of circulating regulatory T cells. Importantly the plasma levels of the T regulatory cell cytokine, IL10, the TH1 cytokines IL12 and IFNγ, the proinflammatory TNF α and immune regulatory IL27 were all highly raised. Furthermore, the level of IL21 that promotes IgG4 production was also very significantly elevated. These results suggest efforts of the immune system to reduce inflammation and suppress an exaggerated Th2 response. A raised serum IgG in the setting of acute kidney injury and in the absence of autoimmunity and chronic infection should encourage an assessment of the IgG subclasses. Prompt steroid treatment of those with a raised IgG4 may reduce ongoing renal damage.     

Managing therapy-associated neurotoxicity in children with ALL

Open in a separate window     

Analysis of 55 cases of adenomatoid odontogenic tumor in an Indian population and review of literature

Background This study reviews the demographic, clinical and radiographic features of adenomatoid odontogenic tumor(AOT) diagnosed in an Indian population over 50 years and also evaluate and compare follicular AOT(F-AOT) and extra-follicular AOT(EF-AOT).Material and Methods 55 diagnosed cases of AOT from 1971-2020 were studied retrospectively. The data regarding the age, sex, location, variant of AOT, duration, clinical features, radiographic appearance, treatment and recurrence were collected and analysed.Results Of the 722 odontogenic tumors diagnosed, 7.6% were AOTs with higher prevalence of extra-follicular (67.3%) than follicular (32.7%) variant. All the tumors were intraosseous with a marked predilection for maxilla over mandible, ratio 2:1. The patients mean age was 19.8 years with slightly higher female predilection (male:female ratio - 1:1.5). The anterior region (76.4%) was more frequently affected and entire quadrant was involved in 21.8% cases. Clinically, asymptomatic, slow-growing swelling was seen in 81.8% cases with duration of 15 days to 10 years. Radiographically, AOT appeared as well-corticated radiolucent lesion. Canine was the most commonly impacted tooth. Recurrence was seen in 3 cases.Conclusions Interestingly, in this series extra-follicular was twice more common than follicular AOT. Few cases involved the entire quadrant or crossed the midline of either jaws. Key words:Adenomatoid odontogenic tumor (AOT), follicular AOT, extrafollicular AOT, Indian population, odontogenic tumor.     

Orbital dermoid cyst

Background:Dermoid cyst, a developmental benign choristoma, is the most common orbital tumor of childhood, arising from ectodermal sequestration along the lines of embryonic fusion of mesodermal processes, lined by keratinized stratified squamous epithelium and expanding slowly due to constant desquamation and dermal glandular elements. Approximately 80% are found in the head and neck region and comprise 3-9% all orbital masses.Purpose:It is mandatory to know about the variable presentations of orbital dermoids and the surgical techniques that can be adopted based on the site, extent, age and aesthetic needs, presence of inflammation and possibility of intraoperative rupture.Synopsis:Orbital dermoids can be classified as juxta-sutural, sutural or soft tissue cysts; superficial or deep; intraosseous or extraosseous, and intraorbital or extraorbital. These smooth, painless, mobile or partially mobile lesions mostly present at the fronto-zygomatic suture with proptosis, displacement, ptosis or diplopia, depending on depth and extent. Therefore, it is important to understand the various presentations and the appropriate surgical techniques.Highlights:We describe the embryological origin, types and clinical features of dermoids in this video and demonstrate the surgical and minimally invasive techniques for their management.Video link: https://youtu.be/-q3xD2igjcQ     

The effect of mutation in the stem of the MicroROSE thermometer on its thermosensing ability: insights from molecular dynamics simulation studies

A large number of bacteria have been found to govern virulence and heat shock responses using temperature sensing RNAs known as RNA thermometers (RNATs). They repress translation initiation by base pairing to the Shine–Dalgarno (SD) sequence at low temperature. Increasing the temperature induces the RNA duplex to unfold and expose the SD sequence for translation. A prime example is the ROSE thermometer module known to regulate the production of the ROSE heat shock protein in Bradyrhizobium japonicum. The unfolding of a 29-nucleotide long MicroROSE RNA element which forms a critical component encompassing the SD sequence, and three mutants that differ from it by deletion of a guanine nucleotide or mutations near the SD and stem regions have been studied using high temperature molecular dynamics simulations. The simulations reveal the progressive manner in which a biologically functional RNA thermometer unfolds. Our simulations reveal that deletion of the highly conserved G10 residue, opposite to the SD region leads to the formation of a stable RNA helix that has lost its thermosensing ability. Mutations of bases A5 → U5 and U25 → A25 near the stem increase the thermosensing ability due to the allosteric effect which leads to a global destabilization effect on the structure. The temperature-dependant regulation of this thermometer has been investigated by estimation of differences in the unfolding paths by calculating individual residue fluctuation, stacking energy, the contact map plot and the lifetime dynamics plot of non-Watson–Crick hydrogen bonds at three different temperatures. Results reveal that partial unfolding at higher temperature starts from the hairpin tetra loop end and terminates at the stem region through the SD associated region. Two canonical hydrogen bonds between U9–A22 and four non-canonical hydrogen bonds between G10–G21 and U6–U24 around the internal loop play an important role in partial melting of the RNA helix. These results demonstrate how small alterations in RNA structure can regulate gene expression and illuminate the molecular basis of the function of an important bacterial regulatory motif.

Mutation induced thermosensing ability of MicroROSE thermometer.     

Primary hyperparathyroidism presenting as severe hypercalcemia with acute pancreatitis in pregnancy

Abstract

Primary hyperparathyroidism presenting first time with severe hypercalcemia is rare in pregnancy. We report a case of primary hyperparathyroidism due to a cystic parathyroid adenoma presenting as severe hypercalcemia with acute pancreatitis in second trimester of pregnancy. Acute pancreatitis was managed by conservative treatment. Hypercalcemia failed to respond to medical management and ultimately responded to ultrasound-guided ethanol ablation of parathyroid adenoma. The delivery was uneventful and patient continues to remain normocalcemic during follow up. As such, ethanol ablation of parathyroid adenoma may be considered during pregnancy in case of failure of response to medical management and when surgical removal of parathyroid adenoma is not safe.