Specificity of autoantibodies in autoimmune thrombocytopenia

In 42 patients with autoimmune thrombocytopenia (AITP) and a positive direct platelet suspension immunofluorescence test (PSIFT), the antigenic specificity of the autoantibodies was studied. Because the autoantibodies were often not detectable in the serum and additional HLA antibodies may disturb the reaction pattern with the platelet panel, we used eluates prepared from the patients' platelets for this study. Thirty-five patients had antibodies equally reactive with normal platelets, irrespective of their antigenic make-up, but not with the platelets from two Glanzmann's disease patients. Absorption and elution experiments in two patients showed that his was probably not due to the presence of a combination of anti-Zwa and anti-Zwb antibodies. Thus, the majority of autoantibodies against platelets seems to be directed against antigenic determinants not present on Glanzmann's disease platelets, but perhaps located on the platelet-membrane glycoproteins IIb and/or IIIa. In ten patients, antibodies of no, or still unknown, specificity were detected. Three of these had additional antibodies not reactive with the platelets of the two Glanzmann patients.     

A human antibody binds to alpha-galactose receptors and mimics the effects of Clostridium difficile toxin A in rat colon

BACKGROUND & AIMS: Nearly all human sera contain an immunoglobulin G antibody (antigalactose) that binds the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc expressed on cells from most mammals but not humans. Because the Clostridium difficile toxin A receptor in rodents contains this trisaccharide, the aim of this study was to examine whether antigalactose could mimic the enterotoxic effects of toxin A and bind to receptors containing this trisaccharide. METHODS: Fluid secretion, [3H]-mannitol permeability, and release of rat mast cell protease II and prostaglandin E2 were measured after luminal exposure of rat colon to either purified human anti-galactose, control immunoglobulin G, toxin A, or buffer. RESULTS: Toxin A (5 micrograms) and antigalactose (250 micrograms) but not control immunoglobulin (250 micrograms) stimulated colonic fluid secretion and caused increased mannitol permeability and rat mast cell protease II release. Antigalactose and toxin A and, to a lesser degree, control immunoglobulin G also stimulated release of prostaglandin E2, but only toxin A produced acute inflammation of rat colonic mucosa. Antigalactose and toxin A bound specifically to a single class of colonic brush border receptors with dissociation constants of 10(-6) mol/L and 5.4 x 10(-8) mol/L, respectively. CONCLUSIONS: Fluid secretion, increased permeability, and mast cell activation occur in rat colon when toxin A or human antigalactose immunoglobulin G bind to receptors bearing the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc. (Gastroenterology 1996 Jun;110(6):1704-12)     

Consequences of increased systolic blood pressure in patients with osteoarthritis and rheumatoid arthritis

OBJECTIVE: To estimate the potential effect on cardiovascular event occurrence and treatment costs associated with increases in systolic blood pressure (SBP) among patients with osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: We used cardiovascular risk prediction models from the Framingham Heart Study and data on risk factors from the Third National Health and Nutrition Examination Survey (NHANES III) to estimate occurrences of ischemic heart disease and stroke over one year among US adults with OA/RA. Separate analyses were conducted for treated hypertensive patients, and untreated hypertensive and normotensive patients, respectively. Published estimates were used to assign costs to these events and to follow care. The effect of incremental increases in SBP on events and costs was then assessed. Monte Carlo simulation was undertaken to assess the range of event occurrence and costs associated with alternative assumptions regarding the distribution of increased SBP in the at-risk population. RESULTS: Of the estimated 30 million adults in the US aged > or = 35 years with OA and RA, roughly 11.8 million (39%) receive pharmacologic treatment for hypertension. Increases in SBP of 1-5 mm Hg were associated with 7,100-35,700 additional ischemic heart disease and stroke events over one year, with corresponding costs (year 2000 USD) of 114-569 million year 2000 USD. A 20 mm Hg increase in SBP experienced by 15% of the at-risk population (equivalent to a population-average 3 mm Hg increase) is associated with about 21,700 additional events (95% CI 19,120, 24,221) and 346 million year 2000 USD (95% CI 305 year 2000 USD, 387 million) in associated costs. CONCLUSION: Relatively small changes in SBP associated with use of common arthritis medications can have a significant effect on the cardiovascular risk profile. It is important that clinicians who treat patients with OA/RA accurately weigh the potential risks of these medications against their benefits.     

Duodenal hematoma: the ring sign in MR imaging

Proper management of duodenal hematoma requires that an accurate diagnosis be made using noninvasive radiological methods. Conventional imaging may be nonspecific if there is no history of trauma or coagulopathy. Two cases of duodenal hematoma that were imaged by magnetic resonance (MR) and computed tomography (CT) are described. In both cases the hematoma had a well-defined concentric ring configuration on MR images, a finding which helped establish the diagnosis. MR imaging may provide tissue-specific characterization of duodenal hematomas.     

Biliary stricture dilatation: multicenter review of clinical management in 73 patients

Eighty-nine biliary strictures in 73 patients who had undergone percutaneous balloon dilatation were reviewed to determine long-term patency rates and clinical management problems. The majority of dilatations were performed in patients with anastomotic strictures (n = 44), iatrogenic strictures (n = 28), and strictures associated with sclerosing cholangitis (n = 17). Patency rates after 36 months or more were 67%, 76%, and 42%, respectively. Complications, mostly minor, occurred in less than 7% of patients. Of patients with significant biliary obstruction, 15% had little or no intrahepatic biliary duct dilatation demonstrated by cross-sectional imaging and/or direct cholangiography. No definite conclusions could be drawn about the utility of long-term internal/external stenting.     

Rapid MR imaging with suspended respiration: clinical application in the liver

The authors demonstrate that it is possible to obtain highly T1-weighted images of the abdomen using a suspended respiration partial saturation (SRPS) method in a breath-holding interval. T2*-weighted images, which reflect tissue T2 as well as variations in the static magnetic field, can also be rapidly obtained. The authors studied five healthy subjects and 19 patients with a variety of liver abnormalities, including benign and malignant hepatic neoplasms, fatty liver infiltration, ascites, and hematoma. On T1-weighted multisection acquisitions, the entire liver can be screened for mass lesions in a single 20-second breath-holding interval. Phase-contrast SRPS images are sensitive to fatty infiltration of the liver. SRPS images are more sensitive to variations in magnetic susceptibility than spin-echo images are, which has been proved to be of value in the detection of hemorrhage. With continued pulse sequence development and clinical study, this method has the potential to become the method of choice for evaluation of the upper abdomen.     

Ferrite particles for bowel contrast in MR imaging: design issues and feasibility studies

Diverse materials with varying physical and magnetic properties have been evaluated as gastrointestinal contrast agents for magnetic resonance (MR) imaging. Uniform marking of the small bowel remains the greatest challenge. Ferrites are magnetically active iron oxide particles that are miscible with water and cause loss of signal on MR images. The decrease in MR signal intensity produced by ferrites occurs with a wide range of iron concentrations (0.1-10 mM) and with both T1- and T2-weighted pulse sequences. These effects of ferrites are explained by predominant T2 shortening with negligible T1 effects. The ferrite preparation used in this study was stable in vitro, with little iron solubilized by acid. Intragastric administration of ferrite (5 mg of iron per kg in 6 ml) routinely marked the small bowel of rats. The authors conclude that ferrites represent a promising new class of contrast agents for gastrointestinal MR imaging.