A case of hypothyroidism with brugada electrocardiographic waveforms.

A 77-year-old man was diagnosed as having hypothyroidism. An electrocardiogram obtained at the time of the first examination revealed Brugada electrocardiographic waveforms in leads V1 to V3. When pilsicainide hydrochloride loading changed the waveforms of the electrocardiographic ST segment, this result suggested an abnormality of the cardiac muscle sodium channels. The Brugada electrocardiographic waveforms disappeared with the normalization of thyroid function. This case is the first report ever of hypothyroidism that presented Brugada electrocardiographic waveforms. The results obtained in this case suggested that thyroid functions changed the waveforms of the electrocardiogram because of its effect on myocardial ion channels.

Human anti-anthrax protective antigen neutralizing monoclonal antibodies derived from donors vaccinated with anthrax vaccine adsorbed.

BACKGROUND: Potent anthrax toxin neutralizing human monoclonal antibodies were generated from peripheral blood lymphocytes obtained from Anthrax Vaccine Adsorbed (AVA) immune donors. The anti-anthrax toxin human monoclonal antibodies were evaluated for neutralization of anthrax lethal toxin in vivo in the Fisher 344 rat bolus toxin challenge model. METHODS: Human peripheral blood lymphocytes from AVA immunized donors were engrafted into severe combined immunodeficient (SCID) mice. Vaccination with anthrax protective antigen and lethal factor produced a significant increase in antigen specific human IgG in the mouse serum. The antibody producing lymphocytes were immortalized by hybridoma formation. The genes encoding the protective antibodies were rescued and stable cell lines expressing full-length human immunoglobulin were established. The antibodies were characterized by; (1) surface plasmon resonance; (2) inhibition of toxin in an in vitro mouse macrophage cell line protection assay and (3) in vivo in a Fischer 344 bolus lethal toxin challenge model. RESULTS: The range of antibodies generated were diverse with evidence of extensive hyper mutation, and all were of very high affinity for PA83~1 x 10-10-11M. Moreover all the antibodies were potent inhibitors of anthrax lethal toxin in vitro. A single IV dose of AVP-21D9 or AVP-22G12 was found to confer full protection with as little as 0.5x (AVP-21D9) and 1x (AVP-22G12) molar equivalence relative to the anthrax toxin in the rat challenge prophylaxis model. CONCLUSION: Here we describe a powerful technology to capture the recall antibody response to AVA vaccination and provide detailed molecular characterization of the protective human monoclonal antibodies. AVP-21D9, AVP-22G12 and AVP-1C6 protect rats from anthrax lethal toxin at low dose. Aglycosylated versions of the most potent antibodies are also protective in vivo, suggesting that lethal toxin neutralization is not Fc effector mediated. The protective effect of AVP-21D9 persists for at least one week in rats. These potent fully human anti-PA toxin-neutralizing antibodies are attractive candidates for prophylaxis and/or treatment against Anthrax Class A bioterrorism toxins.

Human monoclonal antibodies that neutralize anthrax toxin by inhibiting heptamer assembly.

A panel of human anti-anthrax protective antigen IgG1 monoclonal antibodies were evaluated to determine the mechanism of toxin neutralization. AVP-22G12, AVP-1C6 and AVP-21D9 bound to the protective antigen with picomolar affinities to distinct non-overlapping linear epitopes. Two of the antibodies neutralized the anthrax toxin by completely inhibiting the protective antigen oligomer assembly process in vitro.

Treatment of common bile duct obstruction by pancreatic cancer using various stents: single-center experience.

PURPOSE: To compare the effectiveness of various means of stenting in patients with biliary obstruction caused by pancreatic cancer in a retrospective analysis. METHODS: Sixty-two patients with biliary obstruction due to unresectable pancreatic cancer underwent biliary stenting. On the basis of the findings obtained by percutaneous transhepatic cholangiography (10 patients) and endoscopic retrograde cholangiography (52 patients), the site of obstruction was distal to the hilar confluence, predominantly especially in the middle to lower third of the common bile duct. Polyurethane-covered Wallstents (9 mm in diameter) were inserted in 13 patients, while uncovered Wallstents (10 mm in diameter) were used in 10 patients and plastic stents (10 Fr and 12 Fr) were used in 39 patients. RESULTS: Stenting was successful in 34 patients (87.2%) treated with plastic stents and in 22 patients (95.7%) treated with Wallstents. Effective biliary drainage was achieved in 32 out of 34 patients (94.1%) treated with plastic stents and in 21 out of 22 patients (95.5%) treated with Wallstents. The cumulative patency rate was significantly higher for the uncovered and covered Wallstents compared to plastic stents, but was not significantly higher for covered than for uncovered Wallstents. Stent occlusion occurred in 23 patients (70%; all by clogging) from the plastic stent group, in two patients (22%; by tumor ingrowth) from the uncovered Wallstent group, and in one patient (9%; by clogging) from the covered Wallstent group. The survival rate showed no significant difference among the three stent groups. CONCLUSION: The Wallstent is effective for long-term palliation in patients with obstruction caused by pancreatic cancer invading the middle to lower part of the common bile duct. The covered Wallstent can prevent tumor ingrowth, a problem with the uncovered Wallstent. However, it may be necessary to take measures to prevent the migration or clogging of covered Wallstents.