Efficacy of endoscopic hemoclipping for GI bleeding in relation to severity of shock

BACKGROUND/AIMS: To examine the efficacy of prospectively performing endoscopic hemoclipping in patients with severe gastrointestinal bleeding by assessing in relation to the severity of the case. METHODOLOGY: Endoscopic hemoclipping was performed in 44 patients in shock caused by severe gastrointestinal bleeding. The level of severity was categorized using two factors. One factor was the presence or absence of severe shock, and the other was the presence or absence of active bleeding at endoscopy. Age, blood transfusion volume, APACHE III score, coagulopathy, initial hemostatic, rebleeding and mortality rate were recorded in relation to those four subsets. If rebleeding occurred, the systolic blood pressure, heart rate and serum hemoglobin concentration were compared between the initial time of bleeding and rebleeding. RESULTS: Initial hemostasis was successfully achieved in all cases. The severe shock group required significantly more blood transfusions. The most severe subset had the highest APACHE III score, and coagulopathy. Rebleeding occurred in seven cases in the severe shock group only. In the rebleeding group, the systolic body pressure was lower, heart rate was higher, and serum hemoglobin concentration was lower than the non-rebleeding group. Four patients, all in subset 1, died, but no patient died due to gastrointestinal bleeding. CONCLUSIONS: The endoscopic hemoclipping method is very effective for severe gastrointestinal bleeding in shock. The severity of shock was a more important risk factor than the presence of active bleeding. Our category of severity is simple, it reflects the patients' clinical condition accurately, and is very useful for patients with gastrointestinal bleeding.     

Clinical spectrum of mediastinal cysts

OBJECTIVES: Congenital cysts of the mediastinum are an uncommon but important diagnostic group, representing 12 to 30% of all mediastinal masses. The purpose of this study was to review our institutional experience with congenital cysts of the mediastinum, emphasizing the clinical spectrum of the disease. DESIGN: Retrospective study. OBJECTIVES: University hospital unit of general thoracic surgery. METHODS: We retrospectively reviewed the records of 105 patients with cysts of the mediastinum (50 male and 55 female patients) who comprised 13.0% of mediastinal masses over the past 50 years. RESULTS: There were 10 pediatric patients (< 15 years old) and 95 adult patients. The prevalence of cysts in the adult populations was higher than that in children (14.1% vs 7.7%, p < 0.05). There were 47 bronchogenic cysts, 30 thymic cysts, 12 pericardial cysts, 7 pleural cysts, 4 esophageal duplications, 2 meningoceles, 1 thoracic duct cyst, and 2 others. MRI has become a useful tool for providing supplemental data in combination with CT. Overall, 38 patients (36.2%) with mediastinal cysts were symptomatic, including 39.2% with bronchogenic/esophageal cysts, 40% with thymic cysts, and 15.8% with pericardial/pleural cysts. One hundred patients had complete resection of their masses, 3 patients with pericardial diverticulum received a thoracoscopic fenestration without mortality, and 2 patients refused surgery. CONCLUSION: Early recognition of these relatively rare lesions would lead to immediate and appropriate surgical intervention. Early surgical intervention is also important because definitive histologic diagnosis can only be established by means of surgical extirpation.     

Interleukin-18 overproduction exacerbates the development of colitis with markedly infiltrated macrophages in interleukin-18 transgenic mice

BACKGROUND AND AIM: The authors have previously shown that production of interleukin (IL)-18 was increased in the inflamed mucosa of patients with Crohn's disease (CD) and blockade of IL-18 ameliorated the murine model of CD. This demonstrated that IL-18 plays a significant role during intestinal inflammation. However, the initial role of IL-18 during intestinal inflammation was unclear; therefore the susceptibility of IL-18 transgenic (Tg) mice to acute dextran sulfate sodium (DSS)-induced colitis was examined. METHODS: Interleukin-18 Tg and wild-type (WT) mice were fed 2.0% of DSS for 8 days. The total clinical scores (bodyweight loss, stool consistency, and rectal bleeding), colon length and histological scores were assessed. The expressions of surface markers and IL-18 on infiltrating lamina propria mononuclear cells were analyzed immunohistochemistrically. Mesenteric lymph node (MLN) cells were isolated and the expressions of CD4+ T-cell activation markers (CD69, CD25 and IL18R) were analyzed by flow cytometry. RESULTS: The IL-18 Tg mice exhibited an increased susceptibility to DSS-induced colitis, as shown by significantly increased clinical, histological scores, and more severe colonic shortening compared with WT mice. Immunohistochemical analysis revealed a significant increase of IL-18 production and CD11b+ macrophages but not CD4+ T cells in the inflamed mucosa in DSS-fed IL-18 Tg compared with DSS-fed WT mice. Furthermore, MLN cells revealed no evidence of increased CD4+ T-cell activation in DSS-fed IL-18 Tg. CONCLUSIONS: These findings suggest that IL-18 overproduction in the mucosa plays an important role in the marked infiltration of macrophages and exacerbates colitis in IL-18 Tg mice.     

Superior vena cava syndrome due to fibrosing mediastinitis histologically identical to xanthogranulomatous pyelonephritis

We present herein a case of superior vena cava (SVC) syndrome caused by localized fibrosing mediastinitis (FM), which had histological features similar to xanthogranulomatous pyelonephritis (XGP). A 63-year-old woman presented with facial swelling 5 months after undergoing right nephrectomy for XGP. Radiologic investigations of the chest confirmed the presence of SVC obstruction due to an intraluminal tumor. The histological features of the tumor were consistent with those of FM and were very similar to those of XGP. Although the pathogenesis of neither FM nor XGP is known, some pathogenic process of FM and XGP may be the same.     

Tumor necrosis factor-related apoptosis-inducing ligand induces neuronal death in a murine model of HIV central nervous system infection

HIV-1 infection in the brain induces neuronal apoptosis leading to HIV-associated dementia. To explore the underlying mechanism, we developed a murine model by using human peripheral blood mononuclear cell (PBMC)-transplanted nonobese diabetic (NOD)-severe combined immunodeficiency (SCID) (hu-PBMC-NOD-SCID) mice. Administration of lipopolysaccharide (LPS) to HIV-1-infected hu-PBMC-NOD-SCID mice induced infiltration of HIV-1-infected human cells into the perivascular region of the brain and neuronal apoptosis was found in macrophage (M)-tropic but not T cell (T)-tropic HIV-1-infected brains. The apoptotic neurons were frequently colocalized with the HIV-1-infected macrophages that expressed tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). Administration of a neutralizing antibody against human TRAIL but not human TNF-alpha or Fas ligand (FasL) blocked the neuronal apoptosis in the HIV-1-infected brain. These results strongly suggest a critical contribution of TRAIL expressed on HIV-1-infected macrophages to neuronal apoptosis.     

Preventive effect of melatonin on the progression of alpha-naphthylisothiocyanate-induced acute liver injury in rats

The preventive effect of melatonin on the progression of alpha-naphthylisothiocyanate (ANIT)-induced acute liver injury with cholestasis was examined in rats treated once with the hepatotoxin [75 mg/kg body weight (BW), i.p.]. In rats treated with ANIT alone, liver injury with cholestasis occurred 24 hr after treatment and progressed at 48 hr, judging from the serum levels of hepatobiliary marker enzymes and components. Melatonin (10 or 100 mg/kg BW) was orally administered to the ANIT-treated rats, 24 hr after the hepatotoxin treatment at which time hepatic injury had already developed. The administered indoleamine prevented the progression of liver cell damage rather than biliary cell damage more effectively at the higher dose than at the lower dose. In rats treated with ANIT alone, the serum and hepatic concentrations of thiobarbituric acid reactive substances, an index of lipid peroxidation, and the hepatic activity of myeloperoxidase, an index of tissue neutrophil infiltration, increased 24 hr after treatment and further increased at 48 hr. In the liver of rats treated with ANIT alone, Cu,Zn-superoxide dismutase activity decreased 24 hr after treatment and was further reduced at 48 hr, although there was no change in Mn-superoxide dismutase activity. Catalase and Se-glutathione peroxidase activities also decreased at 48 hr, while reduced glutathione concentrations remained increased at 24 and 48 hr. The melatonin administered to the ANIT-treated rats attenuated the increases in serum and hepatic concentrations of thiobarbituric acid reactive substances and the decreases in hepatic activities of Cu,Zn-superoxide dismutase, catalase, and Se-glutathione peroxidase found at 48 hr after the hepatotoxin treatment more effectively at the higher dose than at the lower dose; on the other hand, melatonin treatment had no effect on the increases in hepatic myeloperoxidase activity and reduced glutathione concentration found at 48 h. These results indicate that orally administered melatonin at pharmacological doses prevents the progression of ANIT-induced acute liver injury, mainly liver cell damage, in rats, and suggest that the administered melatonin exerts these preventive effects through its direct and indirect antioxidant actions.     

TNF-alpha rapidly antagonizes the beta-adrenergic responses of the chloride current in guinea-pig ventricular myocytes.

The purpose of this study was to test the hypothesis that tumor necrosis factor-alpha (TNF-alpha) rapidly antagonizes the beta-adrenergic responses of the chloride current and to clarify the intracellular mechanisms responsible for the anti-adrenergic action. The whole-cell patch-clamp technique was used to monitor the anti-adrenergic effects of TNF-alpha on the cAMP-dependent chloride current (I(Cl)) recorded from isolated guinea-pig ventricular myocytes. Ramp pulses (+/-120 mV; dv/dt = +/-0.4 V/s) were applied from the holding potential of -40 mV. TNF-alpha rapidly (<15 min) inhibited the isoproterenol (Iso, 0.1 micromol/L)-induced I(Cl) in a concentration-dependent manner (30-1,000 U/ml, IC (50) = 144 U/ml, n=30). The inhibitory action of TNF-alpha was also observed when I(Cl) had been previously stimulated by 1 micromol/L forskolin (n=5). Prior exposure of myocytes to 5 microg/ml pertussis toxin (PTX) hardly affected the anti-adrenergic action of TNF-alpha (n=4). However, when I(Cl) was induced by both 8-bromo-cAMP (100 micromol/L) and isobutylmethylxanthine (0.1 mmol/L), TNF-alpha (1,000 U/ml) failed to decrease I(Cl) amplitude (n=5). Prior exposure of myocytes to 5 mg/ml pertussis toxin (PTX) hardly affected the anti-adrenergic action of TNF-alpha (n=4). Furthermore, despite of the presence of nitro-L-arginine methyl ester (0.1 mmol/L), a nitric oxide synthase (NOS) inhibitor, TNF-alpha reversed the Iso-induced increase in I(Cl) (n=5). These results suggest that TNF-alpha rapidly antagonizes the beta-adrenergic responses of I(Cl) by reducing cAMP concentration. This anti-adrenergic action is mediated by neither the PTX-sensitive G proteins regulatory pathway nor constitutive NOS activation.     

Ameliorating effect of anti-inducible costimulator monoclonal antibody in a murine model of chronic colitis

BACKGROUND & AIMS: Inducible costimulator (ICOS)/B7RP-1 represents a newly described receptor/ligand pair involved in costimulation of T cells by antigen-presenting cells. We investigated the involvement of the ICOS/B7RP-1 interaction in the pathogenesis of colitis and the therapeutic potential of anti-ICOS monoclonal antibody (mAb) in experimental colitis METHODS: We administered anti-ICOS or anti-B7RP-1 mAb to mice with experimental colitis induced by transfer of CD4(+)CD45RB(high) T cells from normal mice into SCID mice. The ability of CD4(+)CD45RB(high) cells derived from ICOS-/- mice to induce colitis was assessed. Th2 cytokine production and apoptosis in infiltrating T cells was examined after administration of anti-ICOS mAb. RESULTS: ICOS was strongly induced on CD4(+) T cells, and B7RP-1 was expressed by macrophages in the inflamed mucosa of colitic mice. Anti-ICOS mAb, but not anti-B7RP-1, ameliorated chronic colitis when administered in prevention or therapeutic protocols. Transfer of CD4(+)CD45RB(high) T cells from ICOS-/- mice induced colitis. Treatment with anti-ICOS mAb did not enhance the production of Th2 cytokines, but a single dose of anti-ICOS mAb induced massive apoptosis of infiltrating ICOS-expressing T cells. CONCLUSIONS: ICOS/B7RP-1 interactions are not required for the development of colitis. However, treatment with anti-ICOS mAb can prevent and reverse intestinal inflammation by inducing apoptosis of ICOS-expressing T lymphocytes.     

Role for hydrogen peroxide in flow-induced dilation of human coronary arterioles

Flow-induced dilation (FID) is dependent largely on hyperpolarization of vascular smooth muscle cells (VSMCs) in human coronary arterioles (HCA) from patients with coronary disease. Animal studies show that shear stress induces endothelial generation of hydrogen peroxide (H2O2), which is proposed as an endothelium-derived hyperpolarizing factor (EDHF). We tested the hypothesis that H2O2 contributes to FID in HCA. Arterioles (135+/-7 micro m, n=71) were dissected from human right atrial appendages at the time of cardiac surgery and cannulated with glass micropipettes. Changes in internal diameter and membrane potential of VSMCs to shear stress, H2O2, or to papaverine were recorded with videomicroscopy. In some vessels, endothelial H2O2 generation to shear stress was monitored directly using confocal microscopy with 2',7'-dichlorofluorescin diacetate (DCFH) or using electron microscopy with cerium chloride. Catalase inhibited FID (%max dilation; 66+/-8 versus 25+/-7%; P<0.05, n=6), whereas dilation to papaverine was unchanged. Shear stress immediately increased DCFH fluorescence in the endothelial cell layer, whereas treatment with catalase abolished the increase in fluorescence. Electron microscopy with cerium chloride revealed shear stress-induced increase in cerium deposition in intimal area surrounding endothelial cells. Exogenous H2O2 dilated (%max dilation; 97+/-1%, ED50; 3.0+/-0.7x10(-5) mol/L) and hyperpolarized HCA. Dilation to H2O2 was reduced by catalase, 40 mmol/L KCl, or charybdotoxin plus apamin, whereas endothelial denudation, deferoxamine, 1H-(1,2,4)-oxadiazole-[4,3-a]quinoxalin-1-one, or glibenclamide had no effect. These data provide evidence that shear stress induces endothelial release of H2O2 and are consistent with the idea that H2O2 is an EDHF that contributes to FID in HCA from patients with heart disease. The full text of this article is available at http://www.circresaha.org.