Children with celiac disease and high tTGA are genetically and phenotypically different

AIM:To investigate whether celiac disease(CD)patients with tissue-transglutaminase antibody(tTGA)≥100 U/mL are different from patients with lower tTGA levels.METHODS:Biopsy-proven(MarshⅢ)pediatric CD patients(n=116)were prospectively included between March 2009 and October 2012.The biopsies were evaluated by a single pathologist who was blinded to all of the patients’clinical data.The patients were distributed into 2 groups according to their tTGA level,which was measured using enzyme-linked immunoassay:tTGA≥100 U/mL and Ttga<100 U/mL.The patients’characteristics,symptoms,human leukocyte antigen(HLA)genotype and degree of histological involvement were compared between the 2 groups.RESULTS:A total of 34(29.3%)children had tTGA values<100 U/mL and 82(70.7%)tTGA levels of≥100 U/mL.Patients with high tTGA levels had lower average body weight-for-height standard deviation scores(SDS)than did patients with tTGA<100 U/mL(-0.20±1.19 SDS vs 0.23±1.03 SDS,P=0.025).In the low tTGA group,gastrointestinal symptoms were more common(97.1%vs 75.6%,P=0.006).More specifically,abdominal pain(76.5%vs 51.2%;P=0.012)and nausea(17.6%vs 3.7%,P=0.018)were more frequent among patients with low tTGA.In contrast,patients with solely extraintestinal manifestations were only present in the high tTGA group(18.3%,P=0.005).These patients more commonly presented with aphthous stomatitis(15.9%vs 0.0%,P=0.010)and anemia(32.9%vs 11.8%,P=0.019).In addition,when evaluating the number of CD-associated HLA-DQ heterodimers(HLA-DQ2.5,HLA-DQ2.2 and HLA-DQ8),patients with low tTGA levels more commonly had only1 disease-associated heterodimer(61.8%vs 31.7%,P=0.005),while patients with high tTGA more commonly had multiple heterodimers.Finally,patients with tTGA≥100 U/mL more often had a MarshⅢc lesion(73.2%vs 20.6%,P≤0.001)while in patients with low tTGA patchy lesions were more common(42.4%vs6.8%,P≤0.001).CONCLUSION:Patients with tTGA≥100 U/mL show several signs of more advanced disease.They also carry a larger number of CD     

Bench-to-bedside review: Carbon monoxide – from mitochondrial poisoning to therapeutic use

Carbon monoxide (CO) is generated during incomplete combustion of carbon-containing compounds and leads to acute and chronic toxicity in animals and humans depending on the concentration and exposure time. In addition to exogenous sources, CO is also produced endogenously by the activity of heme oxygenases (HOs) and the physiological significance of HO-derived CO has only recently emerged. CO exerts vasoactive, anti-proliferative, anti-oxidant, anti-inflammatory and anti-apoptotic effects and contributes substantially to the important role of the inducible isoform HO-1 as a mediator of tissue protection and host defense. Exogenous application of low doses of gaseous CO might provide a powerful tool to protect organs and tissues under various stress conditions. Experimental evidence strongly suggests a beneficial effect under pathophysiological conditions such as organ transplantation, ischemia/reperfusion, inflammation, sepsis, or shock states. The cellular and molecular mechanisms mediating CO effects are only partially characterized. So far, only a few studies in humans are available, which, however, do not support the promising results observed in experimental studies. The protective effects of exogenous CO may strongly depend on the pathological condition, the mode, time point and duration of application, the administered concentration, and on the target tissue and cell. Differences in bioavailability of endogenous CO production and exogenous CO supplementation might also provide an explanation for the lack of protective effects observed in some experimental and clinical studies. Further randomized, controlled clinical studies are needed to clarify whether exogenous application of CO may turn into a safe and effective preventive and therapeutic strategy to treat pathophysiological conditions associated with inflammatory or oxidative stress.     

SEVERE BRADYARRHYTHMIA IN A PATIENT WITH ALZHEIMER'S DISEASE AND A PATIENT WITH CEREBRAL ISCHAEMIA,BOTH INDUCED BY ACUTE DISTENSION OF THE BLADDER

Two case reports are presented of bradycardia in two elderly patients, which was resistant to atropine but which resolved immediately the acute bladder distension was treated. Generally, a sympathetic cardiac response is expected, and this paradoxical response may be due not only to lesions of the reflex loop involving both the vagal and the sympathetic nerves, but also to endocrinological factors. As acute urinary distension is not uncommon on geriatric wards, bradyarrhythmia due to bladder distension should be considered in elderly patients.     

Cyclosporine as prophylaxis for graft-versus-host disease: a randomized study in patients undergoing marrow transplantation for acute nonlymphoblastic leukemia

Seventy-five patients, 13 to 49 years of age, with acute nonlymphoblastic leukemia in first remission were treated with cyclophosphamide, fractionated total body irradiation, and marrow transplantation from an HLA-identical sibling and randomized to receive either cyclosporine (CSP) (n = 36) or methotrexate (MTX) (n = 39) as prophylaxis for graft-v-host disease (GVHD). All patients engrafted, and 22 who were given CSP and 21 who were given MTX, are alive at 20 to 47 (median, 35) months (P = .5). Engraftment as assessed by granulocyte recovery (P less than .0005) and platelet transfusion requirement (P = .01) was faster in patients on CSP. Twelve patients (33%) on CSP and 22 (56%) on MTX developed acute GVHD of grades II through IV (P = .07) and 15 of 30 on CSP and 14 of 32 on MTX that were at risk developed chronic GVHD. The most frequent causes of death were interstitial pneumonitis and marrow relapse of leukemia, which occurred with similar frequency in both groups. Beneficial effects observed in patients on CSP included less severe mucositis and shorter duration of hospitalization; adverse effects included renal function impairment and hypertension. These data confirm that CSP is a useful immunosuppressant in patients undergoing marrow transplantation but fail to show a significant improvement in survival as compared with the standard regimen of MTX.     

Influence of oxygen tension on the viscoelastic behavior of red blood cells in sickle cell disease

Although the rheological behavior of sickle cell suspensions and of hemoglobin S solutions is known to be strongly dependent on oxygen tension (PO2), little data exist concerning the influence of PO2 on the viscoelasticity of individual HbSS RBC. We have used micropipette aspiration techniques to test the deformation response of both HbSS and control HbAA RBC over a wide range of PO2 at 23 degrees C. Sickled, spiculed HbSS cells were present for PO2 approximately less than 35 mm Hg; for a number of these cells, the deformation response was essentially elastic and an effective membrane rigidity (EMR) was calculated. EMR increased with decreasing PO2 and was approximately 5 to 50 times higher than the equivalent rigidity of oxygenated HbSS RBC. In addition, the rate of membrane deformation was very slow for sickled cells; the half-time for the deformation process increased as PO2 was lowered and was about two orders of magnitude longer than the equivalent time for normal RBC. Other sickled cells exhibited plastic deformation when subjected to comparable deforming forces and experienced irreversible membrane deformation and budding. At all PO2 levels tested, some HbSS RBC remained as discocytes; these cells had normal membrane elasticity and membrane viscosity. Furthermore, changes in PO2 did not affect the membrane properties of HbAA RBC. Thus, gross abnormalities in the deformation response of HbSS RBC were only detected after morphological sickling had occurred. These abnormalities most likely arose from changes in the cytoplasmic HbS viscoelasticity and, if present in vivo, would be expected to impair the flow of HbSS cells in the microcirculation.