Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia.     

The ileoanal J pouch: radiographic evaluation

Endorectal ileoanal pull-through offers an attractive alternative to proctocolectomy and ileostomy for patients with ulcerative colitis, Gardner syndrome, and familial polyposis. To our knowledge, a careful radiographic analysis of the ileum, ileal pouch, and ileoanal anastomosis after ileoanal pull-through has not been reported. Thirty-two patients with ulcerative colitis, Gardner syndrome, and familial polyposis underwent colectomy, mucosal proctectomy, and endorectal ileoanal pull-through of a 15-cm ileal "J" pouch and loop ileostomy. Twenty-five (78%) of 32 of all the pouches radiographically demonstrated spiral folds extending from the middle of the pouch to the pectinate line. Other radiographic features included a mesenteric mass effect, pseudopolyps, and a central lucency that indicated intrapouch sutures. Radiographs provide useful information in the postoperative management of the ileal pull-through.     

Hepatitis delta virus in homosexual men in Sydney.

In countries not generally endemic for hepatitis B, homosexual men who are carriers of hepatitis B surface antigen (HBsAg) have to date largely been spared additional delta virus infection. A focus of homosexually acquired delta has, however, recently been identified in California. To assess the prevalence and risk factors for delta virus infection in homosexual men in Sydney, we tested the sera of 204 homosexual men with acute or chronic hepatitis B infection for total antibody to delta and delta antigen. Total antibody to delta was detected in eight men and delta antigen in one other (4.4% of the total). All men with antibody or antigen had intravenous drug use as a risk factor. Overall nine of 22 (40.9%) male homosexual intravenous drug users had serological evidence of delta infection. Delta positive patients tended to be younger, to have engaged in prostitution, to have more severe chronic liver disease, to be more likely to have a symptomatic acute illness, and to be less likely to express hepatitis Be antigen (HBeAg) in their sera. Though the homosexual transmission of delta infection cannot be concluded from this study, the detection of delta markers in nine homosexual men (including four prostitutes) suggests considerable potential for dissemination of this virus homosexually.     

Headaches in Patients with Pituitary Tumors: a Clinical Conundrum

Purpose of Review

Pituitary tumors account for approximately 17% of all intracranial neoplasms, with the majority being pituitary adenomas. Often, these are found incidentally during a workup for headache; however, the relationship between symptom and pathology remains unclear. The purpose of this article is to review the most recent literature on the epidemiology, pathophysiology, and management of headaches in patients with pituitary tumors.

Recent Findings

The current literature is limited, with few prospective trials focusing on this question. With the exception of pituitary apoplexy, the relationship between headaches and pituitary masses remains unclear. Intervention does not always improve headache and can lead to development of new headache syndromes.

Summary

Further research is needed to better elucidate the relationship between pituitary tumors and headaches. Headache alone is rarely an indication for surgical management of a pituitary adenoma.

     

Disease-modifying effects of edasalonexent,an NF-κB inhibitor,in young boys with Duchenne muscular dystrophy: Results of the MoveDMD phase 2 and open label extension trial

Chronic activation of NF-κB is a key driver of muscle degeneration and suppression of muscle regeneration in Duchenne muscular dystrophy. Edasalonexent (CAT-1004) is an orally-administered novel small molecule that covalently links two bioactive compounds (salicylic acid and docosahexaenoic acid) that inhibit NF-κB. This placebo-controlled, proof-of-concept phase 2 study with open-label extension in boys ≥4-<8 years old with any dystrophin mutation examined the effect of edasalonexent (67 or 100 mg/kg/day) compared to placebo or off-treatment control. Endpoints were safety/tolerability, change from baseline in MRI T₂ relaxation time of lower leg muscles and functional assessment, as well as pharmacodynamics and biomarkers. Treatment was well-tolerated and the majority of adverse events were mild, and most commonly of the gastrointestinal system (primarily diarrhea). There were no serious adverse events in the edasalonexent groups. Edasalonexent 100 mg/kg was associated with slowing of disease progression and preservation of muscle function compared to an off-treatment control period, with decrease in levels of NF-κB-regulated genes and improvements in biomarkers of muscle health and inflammation. These results support investigating edasalonexent in future trials and have informed the design of the edasalonexent phase 3 clinical trial in boys with Duchenne.