CT densities in delayed iodine hepatic scanning

Sixty patients underwent CT scanning of the liver prior to, immediately after, and four hours after intravenous administration of 60% meglumine diatrizoate. Twenty patients received a 50 ml bolus of contrast material (14.6 g of iodine), 20 received 100 ml (29.2 g of iodine), and 20 received 200 ml (58.4 g of iodine). In each group, delayed CT scanning safely raised the inherent density of the liver significantly (increase of 14.3% using 50 ml; 23.9% using 100 ml; and 40.7% using 200 ml). Thus, delayed scanning with doses presently used in abdominal and neurological CT examinations may be helpful in detecting hepatic lesions.     

News media coverage of medication research: reporting pharmaceutical company funding and use of generic medication names

Michael Hochman, MD; Steven Hochman; David Bor, MD; Danny McCormick, MD, MPH

JAMA. 2008;300(13):1544-1550.

Context  The news media are an important source of information about medical research for patients and even some physicians. Little is known about how frequently news articles report when medication research has received funding from pharmaceutical companies or how frequently news articles use generic vs brand medication names.

Objectives  To assess the reporting of pharmaceutical company funding and generic medication name use in news articles about medication studies and to determine the views of newspaper editors about these issues.

Design, Setting, and Participants  We reviewed US news articles from newspaper and online sources about all pharmaceutical company–funded medication studies published in the 5 most prominent general medical journals between April 1, 2004, and April 30, 2008. We also surveyed editors at the 100 most widely circulated newspapers in the United States.

Main Outcome Measures  The percentage of news articles indicating when studies have been pharmaceutical company–funded and the percentage that refer to medications by their generic vs brand names. Also the percentage of newspaper editors who indicate that their articles report pharmaceutical company funding; the percentage of editors who indicate that their articles refer to medications by generic names; and the percentage of newspapers with policies about these issues.

Results  Of the 306 news articles about medication research identified,130 (42%; 95% confidence interval [CI], 37%-48%) did not report that the research had received company funding. Of the 277 of these articles reporting on medications with both generic and brand names, 186 (67%; 95% CI, 61%-73%) referred to the study medications by their brand names in at least half of the medication references. Eighty-two of the 93 (88%) newspaper editors who responded to our survey reported that articles from their publications always or often indicated when studies had received company funding (95% CI, 80%-94%), and 71 of 92 (77%) responding editors also reported that articles from their publications always or often referred to medications by the generic names (95% CI, 67%-85%). However, only 3 of 92 newspapers (3%) had written policies stating that company funding sources of medical studies be reported (95% CI 1%-9%), and 2 of 93 (2%) newspapers had written policies stating that medications should be referred to by their generic names (95% CI 1%-8%).

Conclusion  News articles reporting on medication studies often fail to report pharmaceutical company funding and frequently refer to medications by their brand names despite newspaper editors' contention that this is not the case.

     

First experience with direct, selective factor Xa inhibition in patients with non-ST-elevation acute coronary syndromes: results of the XaNADU-ACS Trial.

BACKGROUND: Unfractionated heparin is widely used in patients with non-ST-elevation acute coronary syndromes but has important limitations. Anticoagulants with predictable kinetics and anticoagulant effects, better efficacy, and greater safety are needed. OBJECTIVE: To investigate the efficacy and safety of a direct, selective factor Xa inhibitor, DX-9065a (Daiichi Pharmaceuticals LTD, Inc.) compared with heparin, in patients with non-ST-elevation acute coronary syndromes. PATIENTS AND METHODS: Patients (n = 402) from the USA, Canada, and Japan were randomized to blinded, weight-adjusted heparin, low-dose DX-9065a, or high-dose DX-9065a. RESULTS: The primary efficacy endpoint of death, myocardial infarction, urgent revascularization, or ischemia on continuous ST-segment monitoring occurred in 33.6%, 34.3%, and 31.3% of patients assigned to heparin, low-dose DX-9065a, and high-dose DX-9065a (P = 0.91 for heparin vs. combined DX-9065a). The composite of death, myocardial infarction, or urgent revascularization occurred in 19.5%, 19.3%, and 11.9% (P = 0.125 for heparin vs. high-dose DX-9065a) of patients; major or minor bleeding occurred in 7.7%, 4.2%, and 7.0% of patients; and major bleeding in 3.3%, 0.8%, and 0.9% of patients. Higher concentrations of DX-9065a were associated with a lower likelihood of ischemic events (P = 0.03) and a non-significant tendency toward a higher likelihood of major bleeding (P = 0.32). CONCLUSIONS: In this small phase II trial, there was a non-significant tendency toward a reduction in ischemic events and bleeding with DX-9065a compared with heparin in patients with acute coronary syndromes. The absence of an effect on ST-monitor ischemia warrants further investigation. These data provide the rationale for adequately powered studies of DX-9065a in acute coronary syndromes or percutaneous intervention.     

Investigations using a novel monoclonal antibody to the glycosylphosphatidylinositol-anchored protein that carries Gregory, Holley, and Dombrock blood group antigens

BACKGROUND: The high-frequency Hy and Gya antigens have been shown to reside on the same protein. Gy(a-) Hy-negative red cells are also Do(a- b-). A mouse monoclonal antibody, 5B10, was produced with specificity related to the human Gregory, Holley, and Dombrock blood group antigens. STUDY DESIGN AND METHODS: The antibody reacted in direct hemagglutination assays, and its specificity was investigated by radioimmunoassay, inhibition assay, and Western blotting. RESULTS: The 5B10 antibody failed to bind to abnormal paroxysmal nocturnal hemoglobinuria red cells and human erythroleukemia cell line K562, but it was weakly reactive with HEL cells. Red cells, but not other circulating hematopoietic cells, express the 5B10 antigen. The 5B10 antibody had a specificity similar but not identical to that of Gya. Gy(a-) Hy-negative red cells reacted extremely weakly with 5B10 antibody, but Gy(a-) Hy-negative red cells treated with a variety of proteases bound 5B10 antibody strongly. This suggests that these cells express a variant form of the protein recognized by 5B10. CONCLUSION: Identification of a monoclonal antibody to this glycosylphosphatidylinositol-linked protein opens a new avenue for investigation of the biochemistry, genetics, and function of the glycosylphosphatidylinositol-linked protein that bears the Gya, Hy, and Do antigens.     

Selective protection against IgG binding to red cells treated with phthalocyanines and red light for virus inactivation

BACKGROUND: Irradiation with red light of red cells (RBCs) containing the photodynamically active phthalocyanine (Pc) dyes is being studied for inactivation of lipid-enveloped viruses. One of the outstanding problems with this treatment is the binding of IgG to RBCs. The effects of oxygen and type I or type II quenchers on this IgG uptake were evaluated. STUDY DESIGN AND METHODS: The Pc compounds used were aluminum phthalocyanine tetrasulfonate (AIPcS4), HOSiPcOSi(CH3)2(CH2)3N(CH3)2 (Pc 4); HOSiPcOSi(CH3)2(CH2)3N+(CH3)3I- (Pc 5); and SiPcOSi[(CH3)2(CH2)3N+(CH3)3](2)2I- (Pc 6). RBCs were analyzed by flow cytometry for the presence of IgG. RESULTS: Irradiation with red light for 30 minutes of RBCs containing either 2 microM Pc 4, 2 microM Pc 5, 2 microM Pc 6, or 6.5 microM AIPcS4 resulted in an uptake of IgG. These conditions completely inactivated the lipid-enveloped vesicular stomatitis virus (VSV) (> 5 log10 kill). IgG uptake was reduced when oxygen was depleted. The addition of reduced glutathione (GSH) or mercaptoethanol prevented the binding of IgG with RBCs treated with AIPcS4, Pc 4, Pc 5, and Pc 6. Specific binding of IgG2 but not of C3d was observed upon irradiation of RBCs with Pc 5 and Pc 6 in the absence of GSH. No gross changes were observed in RBC antigen strength after irradiation with the dyes in the presence of GSH. Inactivation of VSV by Pc plus light was not affected by GSH. CONCLUSION: Sulfhydryl compounds are useful in preventing IgG binding to RBCs following Pc photosensitization. Since virus inactivation proceeds at the same rate in the presence and the absence of sulfhydryl compounds, their addition to treated RBCs should allow crossmatching for transfusion after treatment. The binding of IgG depends to a large extent on the generation of reactive oxygen species.     

Sulindac-induced immune hemolytic anemia

BACKGROUND: Sulindac, a nonsteroidal, anti-inflammatory, indene-derived drug, caused life-threatening immune hemolytic anemia in an individual with back pain. CASE REPORT: A patient was admitted to the hospital with immune hemolytic anemia and kidney and liver failure after several days ingestion of sulindac. The direct antiglobulin test was positive with polyspecific and monospecific anti-IgG but not with anti-C3. The eluate did not react in routine tests but reacted strongly after the addition of sulindac. The serum contained a sulindac-dependent antibody reacting to a titer of 32. The sulindac-dependent antibody was of both IgG and IgM classes and had no apparent blood group specificity. The antibody agglutinated red cells from humans and chimpanzees but not from chickens, rabbits, or sheep, which implied that a specific component on human and chimpanzee red cells was needed for reactivity. The antibody reacted with red cells treated with trypsin, papain, pronase, dithiothreitol, and sialidase. With aggressive medical care, the patient's condition improved. CONCLUSION: These findings appear compatible with the so-called immune complex mechanism for drug-induced immune hemolytic anemia. Physicians are alerted to the severe nature of this syndrome.     

Clinical utility of plasma membrane vesicles expressing recombinant glycophorin A-encoded blood group antigens

BACKGROUND: Although the genes encoding most of the major blood group determinants are now cloned, recombinant blood group antigens are not commonly used in the clinical laboratory. This study assessed the feasibility of using plasma membrane vesicles expressing recombinant glycophorin A blood group antigens as soluble immunoadsorbants. STUDY DESIGN AND METHODS: Chinese hamster ovary cells were transfected with plasmids containing the cDNA encoding the M- or N-allele of glycophorin A. Plasma membrane vesicles were chemically induced from stable, high- expressing cell lines. Antibodies were assessed for reactivity in hemagglutination-inhibition assays. RESULTS: Eight anti-M antibodies were evaluated. Vesicles expressing the M-allele of glycophorin A neutralized four antibodies (two murine monoclonals; two human sera), while the activity of four human sera was unaffected. Three anti-N reagents were also evaluated (murine monoclonal antibody; rabbit polyclonal antibody; Vicia graminea lectin). All were neutralized by vesicles expressing the N-allele of glycophorin A. There was no detectable neutralization of other clinically significant blood group antibodies. CONCLUSIONS: Plasma membrane vesicles expressing recombinant glycophorin blood group determinants may prove to be useful reagents in the clinical laboratory. However, the partial failure of M antibody recognition requires further study. This general approach could be utilized for any similarly expressed recombinant blood group antigen.     

Engraftment with peripheral blood stem cells collected by large-volume leukapheresis for patients with lymphoma

Seven patients with refractory lymphomas underwent marrow reconstitution with peripheral blood stem cells (PBSCs) harvested by large-volume leukapheresis (LVL). PBSCs were collected from all patients more than 1 month after the last cycle of chemotherapy, and no patient received growth factors. The median number of LVL procedures performed per patient was 4.5, with a mean volume of 24.5 L of blood processed per procedure to obtain 7 x 10(8) mononuclear cells per kg. Autologous PBSCs and platelets were frozen at a controlled rate in plasma and 10-percent dimethyl sulfoxide and stored in the vapor phase of liquid nitrogen. This group of patients was compared to a control group (n = 18) who received medullary marrow (MM) transplants for the same diagnoses under the same protocols during the same period. Posttransplant days to white cell engraftment (PBSC = 17, MM = 15.5) were no different. Days to platelet independence were significantly longer in the LVL PBSC group (PBSC = 33, MM = 16; p < 0.05). This pattern of engraftment is typical of patients treated in this manner. Although Day 0 platelet counts (PBSC = 75.5 x 10(9)/L, MM = 85 x 10(9)/L) and total single-donor unit platelet use (PBSC = 8, MM = 9) were no different, Day 1 platelet counts (PBSC = 128 x 10(9)/L, MM = 61.5 x 10(9)/L; p < 0.05) and Day 14 platelet use (PBSC = 5, MM = 8; p < 0.05) were significantly different, because of the transfusion of cryopreserved autologous platelets with PBSCs on Day 0.