Hyperinsulinaemia and Na+, K+ -ATPase activity in thyrotoxic periodic paralysis

OBJECTIVE Thyrotoxic periodic paralysis (TPP) usually follows a heavy carbohydrate meal and this may be explained by hyperinsulinaemia stimulating Na⁺, K⁺ -ATPase activity. To clarify this the effect of glucose load on serum insulin concentration and platelet Na⁺, K⁺ -ATPase activity In thyrotoxic periodic paralysis (TPP) was examined. DESIGN In all subjects a standard 75-g glucose tolerance test was done and blood samples were taken at 0, 1 and 2 hours. SUBJECTS Twenty-five healthy controls (8 M and 17 F), 17 uncomplicated thyrotoxic patients (7M and 10 F), 15 TPP patients who presented with paralysis and 4 TPP patients after treatment with antithyrold drugs. MEASUREMENTS Plasma glucose was measured by the glucose oxidase method, serum insulin by radioimmunoassay and platelet Na⁺, K⁺ -ATPase by the release of phosphate from ATP. RESULTS TPP patients showed glucose intolerance (area under the curve (AUC) 16·5 ± 4·4 (mean ± SD) In TPP compared to 12·9 ± 4·5 In controls (P < 0·01) and hyperinsulinaemia (AUC 189·6 ±100·6 vs 98·5 ±53·4, P < 0·001). In uncomplicated thyrotoxicosis the results were similar to that in healthy controls. Platelet Na⁺, K⁺ -ATPase were significantly higher in thyrotoxic patients compared to controls and In TPP patients were even higher. Ingestion of glucose increased platelet Na⁺, K⁺ -ATPase in all groups. AUC for platelet Na⁺, K⁺ -ATPase in TPP patients were significantly higher than in uncomplicated thyrotoxicosis (601 ±99·3 vs 482 ± 109·4, P < 0·01) or healthy controls (320 ± 107·3). In the 4 TPP patients studied after antithyroid treatment the results were similar to healthy controls. CONCLUSION Patients with thyrotoxic periodic paralysis have hyperinsulinaemia and this is accompanied by higher Na⁺, K⁺-ATPase activity.     

Anhidrotic ectodermal dysplasia presenting as nasal myiasis

An interesting case of anhidrotic Ectoderml Dysplasia (A.E.D.) which came with epistaxix, headache and maggots in nose is presented. Histopathology of forearm shin, scalp and Exercise test helped to confirm the diagnosis, AED is an X-linked recessive condition and has no cure but symptomatic treatment along with heat protection and protection of eyes especially in summer season has a role to play in the management of these cases.     

Soft tissue sarcomas: ultrasonographic evaluation of local recurrences

OBJECTIVE: The diagnosis of early local recurrence of soft tissue sarcomas, especially in those treated with surgery and radiotherapy, is a difficult clinical problem. Financial constraints led us to use ultrasonography instead of CT or MR imaging. The aim of this study was to evaluate the role of ultrasonography (US) in detecting local recurrence. METHODS AND RESULTS: Fifty patients with previous treatment for soft tissue sarcomas were evaluated prospectively for recurrence by US and histopathology. Seven of the 50 patients were clinically suspected to have recurrent tumour. Ultrasonography showed recurrence in 26, no recurrence in 18, benign disease in four and was indeterminate in two cases. Ultrasonography was instrumental in guiding fine needle aspiration biopsies of small local recurrences and indeterminate lesions in 17 patients. In the sonographically tumour positive patients, histopathology confirmed recurrence in 24; one case had benign disease and one patient refused surgery. Thirteen of the 18 sonographically tumour negative patients were operated upon; all were negative for tumour on histopathology. Both the indeterminate cases showed recurrence on histopathology. The benign cases were confirmed by histopathology correlation. Ultrasound guided fine needle aspiration cytology (FNAC) was positive in 14 out of 17 patients (88%). The sensitivity and specificity of US was 92.30% and 94.4% respectively. CONCLUSION: Our study concludes that US is an extremely useful and cost effective method in the detection of early local recurrences of soft tissue sarcomas and should therefore be used for initial routine follow-up and guided biopsies.     

Aneurysmal bone cysts express vascular markers.

Recently, clonal chromosome abnormalities have been identified in the mural spindle cells in aneurysmal bone cysts (ABCs), but the nature of the cystic spaces is unclear. Endothelial injury has been suggested as a mechanism of aneurysmal formation in these lesions, but few studies have surveyed vascular markers in ABCs. We stained 25 primary aneurysmal bone cysts with a variety of antibodies that stain vessels. Antibody to factor 8 stained the edge of ABC cavities in almost all cases, and antibodies to VEGF-C, GLUT-1, and smooth muscle actin stained the edge of the cavities in approximately half the cases. Antibodies to D2-40 and CD34 also stained the edge of the cavities in some cases. These results suggest that the cavities in ABCs are related to vasculature and support the theory that vascular injury may be important in the pathogenesis of ABCs.     

Effect of Different Rituximab Doses on B Cell Count,Anti-A/B Antibody Titer,Graft Function,and Infectious Complications in ABO-Incompatible Renal Transplantation: A Prospective Study

BackgroundABO-incompatible kidney transplantation (ABOiKT) has been accepted as a viable and cost-effective modality with outcomes comparable to ABO-compatible transplants, but there is a concern regarding higher infectious complications in ABOiKT because of the heightened immunosuppression.The desensitization protocol normally includes antibody removal, B cell depletion by rituximab (RTX), and immunomodulation with intravenous immunoglobulin. Efforts have been made over the years to decrease the dose of RTX in an effort to decrease the infective complications. There is limited literature about the minimum effective dose of RTX, which can cause an effective B cell depletion. This prospective study was designed to correlate the RTX dose with peripheral absolute B cell count, graft function, graft and patient survival, and infective complications.MethodsThis study included 52 adult ABOiKT recipients with anti-A/B antibody titer up to a maximum of 1:512. The participants were divided into 2 groups of 26 each according to the RTX dosage used: Group A received 100 mg/patient, and Group B received 200 mg/patient. RTX was given 14 days prior to transplant after B cell measurement by flow cytometry. The outcomes were compared after 1 year of follow-up.ResultsBoth the dosages effectively depleted the absolute B cell count. Although patient survivals, graft survival, graft function, acute rejection episodes, and post-transplant hospital stay were similar in both groups, infective complications were significantly higher in group B.ConclusionA low dose (100 mg/patient) of RTX produces effective depletion of B cells while lowering the infective complications in ABOiKT.     

Urinary bladder inflammation induces changes in urothelial nerve growth factor and TRPV1 channels

Background and Purpose

The urinary bladder urothelium expresses various receptors and in response to chemical and mechanical stimuli releases mediators, thereby modulating bladder sensory pathways. Transient receptor potential vanilloid 1 (TRPV1) ion channels and nerve growth factor (NGF) in those cells are implicated in this modulatory effect and play a role in sensitizing pain-related afferent pathways during inflammation. In this study, we investigated the interaction between NGF and TRPV1 channels in urothelial cells.

Experimental Approach

Urothelial cells from female Sprague-Dawley rat bladders were cultured to quantify membrane expression of TRPV1 channels and capsaicin-induced ATP release in the presence of NGF alone or with TrKA or PI3K inhibitors. Pain scores from rats with cyclophosphamide (CYP)-induced bladder inflammation were assessed after treatment with a TrkA antagonist. Bladders (from control and CYP rats) were collected and analysed for NGF content and TRPV1 channel expression.

Key Results

Cultured cells responded to NGF with increased TRPV1 channel expression in the cell membrane and increased release of ATP. Both responses were blocked by either a TrkA antagonist or a PI3K inhibitor. Treatment in vivo with the TrkA antagonist alleviated pain symptoms and reduced CYP-induced NGF overexpression in the mucosa. Furthermore, in urothelial cells from animals with bladder inflammation, expression of TRPV1 channels in the membrane was significantly increased.

Conclusions and Implications

During bladder inflammation, increased production of NGF in urothelial cells induced increased expression and activity of TRPV1 channels in the cell membrane. This effect was primarily mediated by the PI3K pathway.