No abstract

No abstract

No abstract

BackgroundMore than twenty years following the end of the 1990–1991 Gulf War it is estimated that approximately 300,000 veterans of this conflict suffer from an unexplained chronic, multi-system disorder known as Gulf War Illness (GWI). The etiology of GWI may be exposure to chemical toxins, but it remains only partially defined, and its case definition is based only on symptoms. Objective criteria for the diagnosis of GWI are urgently needed for diagnosis and therapeutic research.ObjectiveThis study was designed to determine if blood biomarkers could provide objective criteria to assist diagnosis of GWI.DesignA surveillance study of 85 Gulf War Veteran volunteers identified from the Department of Veterans Affairs Minnesota Gulf War registry was performed. All subjects were deployed to the Gulf War. Fifty seven subjects had GWI defined by CDC criteria, and 28 did not have symptomatic criteria for a diagnosis of GWI. Statistical analyses were performed on peripheral blood counts and assays of 61 plasma proteins using the Mann-Whitney rank sum test to compare biomarker distributions and stepwise logistic regression to formulate a diagnostic model.ResultsLymphocyte, monocyte, neutrophil, and platelet counts were higher in GWI subjects. Six serum proteins associated with inflammation were significantly different in GWI subjects. A diagnostic model of three biomarkers—lymphocytes, monocytes, and C reactive protein—had a predicted probability of 90% (CI 76–90%) for diagnosing GWI when the probability of having GWI was above 70%.SignificanceThe results of the current study indicate that inflammation is a component of the pathobiology of GWI. Analysis of the data resulted in a model utilizing three readily measurable biomarkers that appears to significantly augment the symptom-based case definition of GWI. These new observations are highly relevant to the diagnosis of GWI, and to therapeutic trials.

Summary This article aims to offer an updated review of the effects of smoking on inflammatory bowel disease, and provide a review of the methods of achieving smoking cessation. A systematic review of Embase and Medline databases was conducted. Smoking causes opposing effects on ulcerative colitis and Crohn's disease. The odds ratio of developing ulcerative colitis for smokers compared with lifetime non‐smokers is 0.41. Conversely, smokers with Crohn's disease have a more aggressive disease requiring more therapeutic intervention. Smoking cessation is associated with a 65% reduction in the risk of a relapse as compared with continued smokers, a similar magnitude to that obtained with immunosuppressive therapy. Although difficult to achieve smoking cessation can best be encouraged by accessing appropriate counselling services, nicotine replacement therapy and bupropion. Using a combination of these treatments there is an improved chance of success of up to 20% compared with an unassisted quit attempt. Smoking cessation unequivocally improves the course of Crohn's disease and should be a primary therapeutic aim in smokers with Crohn's disease.

After surgery, enoxaparin, 40 mg once daily or 30 mg every 12 hours, is more effective than a regimen of 10 mg once daily to prevent deep venous thrombosis in patients having elective hip replacement surgery. The regimens of 40 mg once daily and 30 mg every 12 hours provided prophylaxis similar to the most effective drug treatments previously reported. The incidence of hemorrhagic episodes with the regimens of 40 mg once daily and 30 mg twice daily was higher than that observed with 10 mg once daily; however, major hemorrhage occurred in only 4% to 5% of patients receiving the higher-dose regimens. The risk-to-benefit ratio supports the use of enoxaparin as a therapeutic agent to prevent deep venous thrombosis in these patients.

Human platelet thromboxane A2/prostaglandin H2 (TXA2/ PGH2) receptors are linked to phosphoinositide-specific phospholipase C (PI-PLC) via a G protein tentatively identified as a member of the Gq class. In contrast, platelet thrombin receptors appear to activate PI-PLC via other unidentified G pro-, teins. Platelets from most dogs are TXA2 insensitive (TXA2-); i.e., they do not aggregate irreversibly or secrete although they bind TXA2, but they respond normally to thrombin. In contrast, a minority of dogs have TXA2-sensitive (TXA2+) platelets that are responsive to TXA2. To determine the mechanism responsible for TXA2-platelets, we evaluated receptor activation of PI-PLC. Equilibrium binding of TXA2/PGH2 receptor agonists, 1251IBOP and 13H1U46619, and antagonist, 13H1SQ29,548, revealed comparable high-affinity binding to TXA2-, TXA2+, and human platelets. U46619-induced PI-PLC activation was impaired in TXA2-platelets as evidenced by reduced (a) phosphorylation of the 47-kD substrate of protein kinase C, (b) phosphatidic acid (PA) formation, (c) rise in cytosolic calcium concentration, and (d) inositol 1,4,5 trisphosphate (IP3) formation, while thrombin-induced PI-PLC activation was not impaired. GTPase activity stimulated by U46619, but not by thrombin, was markedly reduced in TXA2-platelets. Antisera to Gq class a subunits abolished U46619-induced GTPase activity in TXA2-, TXA2+, and human platelets. Direct G protein stimulation by GTPyS yielded significantly less PA and IP3 in TXA2-platelets. Immunotransfer blotting revealed comparable quantities of Gq class a-subunits in all three platelet types. Thus, TXA2-dog platelets have impaired PI-PLC activation in response to TXA2/PGH2 receptor agonists secondary to G protein dysfunction, presumably involving a

The myelodysplastic syndromes represent a prognostically diverse group of disorders. Their study has recently been facilitated by the classification proposed by the French-American-British (FAB) Cooperative Group. Using this scheme it is now possible to define more precisely their natural history and clinical relationship to acute leukaemia. Using the longitudinal case control technique, we reviewed the clinical data and morphology of 69 patients (all elderly males) with chronic irreversible haematological cytopenia and dysplasia. Applying FAB criteria we found: refractory anaemia (RA) in 43%; sideroblastic anaemia (RA-S) in 33%; refractory anaemia with excess blasts (RAEB) in 13%; RAEB in transformation (RAEB-T) in 9% and chronic myelomonocytic leukaemia (CMML) in 1%. The median survival for the entire group was 27 months (RA, 52; RA-S, 29; RAEB, 12; RAEB-T 11; and CMML, 2 months). Short survival was predicted by transfusion requirement and other manifestations of severe cytopenia, as well as by myeloid immaturity. The presence or absence of sideroblastosis did not correlate with survival. Acute leukaemia developed in only eight patients (12%), six of whom initially had RA. Leukaemic transformation was not predicted by progressive cytological immaturity. This study demonstrates that even in the absence of leukaemic transformation, chronic myelodysplasia is a lethal haematological disorder.