Localized bullous pemphigoid in a patient with primary lymphoedema tarda

We report a case of localized bullous pemphigoid (BP) in a woman patient with primary lymphoedema tarda. There is only one previous case reported of localized pemphigoid in an area of lymphoedema, this being of the cicatricial variant. Slow circulation in the lymphatic vessels, increased capillary permeability with preferential localization of antibodies in the area, and potential cleavage of the epidermal junction due to increased hydrostatic pressure leading to autoimmunity, have all been advocated as possible pathogenic mechanisms. Nevertheless, we consider that the mechanism by which localized pemphigoid arises on lymphoedema remains elusive, based on a previous case of generalized BP sparing an area of postsurgical lymphoedema.     

Apoptosis of ileal Peyer's patch B cells is increased by glucocorticoids or anti-immunoglobulin antibodies

The ileal Peyer's patch (PP) in sheep plays a central role in the development and production of B cells. Associated with a tremendous amount of B cell proliferation in this site is the extensive diversification of the Ig repertoire by somatic hypermutation. Very few (<5%) of the B cells produced in the ileal PP differentiate and emigrate; instead, the vast majority of these cells soon die, and we have previously shown that death is associated with apoptosis. When placed in culture, ileal PP B cells die rapidly by apoptosis, such that after 24h, 60 ± 1 % of DNA is fragmented. Here, we show that the extent of this spontaneous B cell apoptosis in culture, as quantitated by DNA fragmentation, was significantly increased in a dose-dependent manner by the glucocorticoids hydrocortisone or dexamethasone. Furthermore, treatment of lambs with 2–2.5 mg/kg of dexamethasone resulted in a marked increase in the number of apoptotic cells in the ileal PP and an increase in ileal PP B cell DNA fragmentation to 20 ± 6%, compared with 2.4 ± 0.1 % in untreated lambs. Anti-immunoglobulin (Ig) antibodies also increased the extent of DNA fragmentation in cultured ileal PP B cells. After 24 or 48 h of culture with anti-Ig (PIg47A), DNA fragmentation was 74 ± 2 % and 75 ± 3 %, respectively. Ileal PP B cells are rescued from apoptosis by agents that activate protein kinase C and increase cytosolic Ca²⁺, and here we show that this treatment also results in apoptotic rescue in the presence of dexamethasone or anti-Ig. We speculate that the apoptosis of ileal PP B cells in situ may be modulated by glucocorticoids and by the cross-linking of surface Ig. Apoptosis, induced by a signal through surface Ig, may be an important mechanism in the deletion of self-reactive B cells during the expansion of the Ig repertoire in the ileal PP.     

Study of a cross-linked hydrogel of Karaya gum and Starch as a controlled drug delivery system

Abstract

A cross-linked hydrogel was synthesized using a hybrid backbone of karaya gum starch and grafted with polyacrylic acid. It showed a maximum swelling ratio (SR) of 30.5?g/g at pH 10 and was explored as an oral drug delivery carrier using paracetamol and aspirin as model drugs. In vitro release experiments revealed that maximum drug release at pH 7.4 in comparison to pH 1.2 (simulated intestinal vs gastric fluid) and neutral medium. The release profiles of these drugs showed no initial burst. It also showed good hemocompatibilty and non-cytotoxicity for its employment as a site specific drug delivery agent.     

Platelet glycoprotein IIb/IIIa inhibition using eptifibatide with primary coronary stenting for acute myocardial infarction: a 30-day follow-up study.

The results of primary coronary stenting for acute myocardial infarction (AMI) have been reported to improve significantly with the concomitant administration of platelet glycoprotein IIb/IIIa inhibitor abciximab. There are, however, no data available with the use of eptifibatide, a more cost-effective, small-molecule GP IIb/IIIa blocker with a shorter half-life. In a prospective multicenter feasibility and efficacy study, we assigned 55 consecutive patients with AMI being taken up for primary stenting to receive eptifibatide just before the procedure (two boluses of 180 microg/kg 10 min apart and a 24-hr infusion of 2 microg/kg/min). Clinical outcomes were evaluated at 30 days after the procedure. The angiographic patency of the vessel with TIMI flow rates, TIMI myocardial perfusion (TMP) grade, and corrected TIMI frame counts were assessed at the end of procedure and before hospital discharge. At 30 days, the primary endpoint, a composite of death, myocardial infarction, and urgent target vessel revascularization (TVR) was seen in 12.7% of patients. The TIMI 3 and TMP grade 3 flow, which was seen in 93% and 86% of patient, respectively, at the end of the procedure, declined to 86% and 78%, respectively (P < 0.05) before hospital discharge. Corrected TIMI frame counts also decreased from 25.7 +/- 7.2 to 22.9 +/- 6.8 (P < 0.05). There were five (9.1%) instances of subacute thrombosis (SAT) presenting as AMI, needing urgent TVR in all, within 3-5 days of the primary procedure. No excessive bleeding complication, directly attributable to the use of eptifibatide, was observed. The study was terminated prematurely because of an unacceptable SAT rate. Administration of eptifibatide along with primary stenting for AMI is associated with a high TIMI 3 and TMP grade 3 flow acutely. However, these flows decline significantly before hospital discharge and lead to a high rate of SAT. The dosage and duration of infusion of eptifibatide in this setting needs further evaluation.     

Effectiveness of sotalol as first-line therapy for fetal supraventricular tachyarrhythmias

Fetal supraventricular tachycardia (SVT) and atrial flutter (AF) can be associated with significant morbidity and mortality. Digoxin is often used as first-line therapy but can be ineffective and is poorly transferred to the fetus in the presence of fetal hydrops. As an alternative to digoxin monotherapy, we have been using sotalol at presentation in fetuses with SVT or AF with, or at risk of, developing hydrops to attempt to achieve more rapid control of the arrhythmia. The present study was a retrospective review of the clinical, echocardiographic, and electrocardiographic data from all pregnancies with fetal tachycardia diagnosed and managed at a single center from 2004 to 2008. Of 29 affected pregnancies, 21 (16 SVT and 5 AF) were treated with sotalol at presentation, with or without concurrent administration of digoxin. Of the 21, 11 (6 SVT and 5 AF) had resolution of the tachycardia within 5 days (median 1). Six others showed some response (less frequent tachycardia, rate slowing, resolution of hydrops) without complete conversion. In 1 fetus with a slow response, the mother chose pregnancy termination. The 5 survivors with a slow response were all difficult to treat postnatally, including 1 requiring radiofrequency ablation as a neonate. One fetus developed blocked atrial extrasystoles after 1 dose of sotalol and was prematurely delivered for fetal bradycardia. Three grossly hydropic fetuses with SVT showed no response and died within 1 to 3 days of treatment. In conclusion, transplacental sotalol, alone or combined with digoxin, is effective for the treatment of fetal SVT and AF, with an 85% complete or partial response rate in our series.