[The children from Zanzibar, hepcidin and iron].
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Anemia↗
Biomedical subjects
A Hadengue
Publications and source records attributed to A Hadengue.
[Cholestasis in adults. 1. Diagnostic procedure approach].
Cholestasis results abnormal biliary excretion, from the hepatocyte to the ampulla of Vater. Diagnosis of the cause of cholestasis is guided by liver ultrasonography, which can be done at the bedside. Management is then dictated by the level of obstruction. In intrahepatic cholestasis (without bile duct dilatation at ultrasonography), the workup will include blood tests for liver disease and liver biopsy will be discussed case by case. In extrahepatic cholestasis (with bile duct dilatation at ultrasonography), a multidisciplinary approach will involve the radiologist, the surgeon, as well as the endoscopist, and delineate the role of magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP).
Algorithms↗
[Cholestasis in adults. 2. Clinical signs and symptomatic treatment].
Cholestasis, a frequent occurrence in clinical practice, can be suspected when confronted to clinical signs (pruritus and jaundice) and/or increased blood level of alkaline phosphatases, gammaglutamyl transpeptidase and/or conjugated bilirubin. This short review will deal with the management of clinical manifestations and extrahepatic complications, whatever the cause of cholestasis. The management according to etiology will be dealt with in a separated chapter.
Cholestasis↗
[Clinical management of a patient with alcoholic cirrhosis].
Prolonged abstinence from alcohol is crucial in the management and prognosis of a patient with alcoholic cirrhosis. It is also important to prevent complications such as variceal bleeding, hepatocellular and extrahepatic cancers, and malnutrition. Liver transplantation should be considered in patients with persistent liver failure in spite of complete cessation of alcohol consumption. We provide some recommendations in commonly encountered clinical situations for compensated and decompensated alcoholic cirrhosis.
Decision Trees↗
[Therapy of chronic hepatitis B].
The aim of chronic hepatitis B therapy is to suppress hepatitis B virus replication, to control disease activity and progression towards cirrhosis. The first-line drug is the pegylated interferon a, which suppresses HBV replication in 40% of cases, albeit burdened with several contraindications and side effects. Lamivudine, a nucleoside analog inhibiting HBV reverse transcriptase, is indicated in case of failure or contraindication to interferon, may however lead to the selection of resistant mutant HBV strains (20% yearly). In that case, adefovir is indicated and has a lower risk of selection of resistant strains (5% yearly). More effective drugs (telbivudine and entecavir) will soon be available in Switzerland. Two inhibitors of HIV (tenofovir and emtricitabine) may also be used to treat hepatitis B in selected cases. Drug combinations, although supported by theoretical considerations, bring no known clinical benefit and are not reimbursed.
Antiviral Agents↗
[Persistent diarrhea in the returned traveler].
Persistent diarrhea in a returned traveler is a frequent presenting complaint and may result from three etiologic groups: persistant infections, non-infectious post-gastroenteritis processes (in particular postinfectious irritable bowel syndrome) and appearance of an unrelated cause of chronic diarrhea. This article reviews the most frequent diseases involved and provides management guidelines for primary care physicians.
Chronic Disease↗
Peroxisome proliferator-activated receptor-alpha and -gamma mRNA levels are reduced in chronic hepatitis C with steatosis and genotype 3 infection.
BACKGROUND: Steatosis in chronic hepatitis C is associated with inflammation and accelerated fibrogenesis. AIM: To assess the contribution of peroxisome proliferator-activated receptor-alpha and -gamma to the pathogenesis of hepatitis C virus associated steatosis is unknown. METHODS: We measured peroxisome proliferator-activated receptor (PPAR)-alpha and -gamma mRNA by quantitative polymerase chain reaction in liver biopsies of 35 genotype 1 and 22 genotype 3 infected patients and in Huh7 cells expressing hepatitis C virus 1b or 3a core protein. RESULTS: PPAR-alpha mRNA was significantly reduced in livers of patients with genotype 3 compared with genotype 1. Steatosis was associated to a decreased expression of PPAR-alpha in genotype 1, but not in genotype 3. PPAR-gamma expression was significantly lower in genotype 3 compared with genotype 1 and steatosis was associated to decreased levels of PPAR-gamma, but only in genotype 1. There was no significant relationship between PPARs mRNA levels and liver activity or fibrosis. Expression of the hepatitis C virus 3a core protein was associated with an increase in triglyceride accumulation and with a significant reduction of PPAR-gamma mRNA compared with hepatitis C virus 1b. CONCLUSIONS: The presence of steatosis and hepatitis C virus genotype 3 are both associated with a significant down-regulation of PPARs. These receptors, and also additional factors, seem to play a role in the pathogenesis of hepatitis C virus-associated steatosis.
Adult↗
The role of junctional adhesion molecule C (JAM-C) in acute pancreatitis.
The recruitment of inflammatory cells contributes significantly to tissue injury in acute pancreatitis. This process implies several molecular interactions between circulating and endothelial cells. The adhesion molecule junctional adhesion molecule C (JAM-C) is involved in leukocyte transendothelial migration and it can form homophilic (JAM-C/JAM-C) and heterophilic interactions with the leukocyte integrin alpha(M)beta(2). In this study, the effect of early administration of monoclonal antibodies directed against JAM-C in cerulein-induced acute pancreatitis was assessed. This reagent significantly blocked influx of leukocytes, release of serum amylase, secretion of inflammatory cytokines, and acinar cell necrosis. These effects were rapid and protected against tissue injury throughout the duration of the model. Conversely, cerulein-induced acute pancreatitis was more severe in transgenic mice overexpressing JAM-C on endothelial cells under the control of the Tie2 promoter. It is proposed that JAM-C expressed by endothelial cells contributes to the pathophysiology of acute pancreatitis and could be considered a target for clinical applications.
Acute Disease↗
In vivo microscopic examination of the esophagus for the detection of cancer before liver transplantation in patients with alcoholic cirrhosis.
Esophageal squamous-cell carcinoma is relatively common in alcohol and tobacco abusers, and it can develop rapidly after liver transplantation. We report the early detection of an esophageal squamous-cell carcinoma in a patient with alcoholic cirrhosis, diagnosed during the pre-enlistment work-up that he was undergoing before liver transplantation. This lesion had not been detected at standard endoscopy, but was well characterized using in vivo staining and microscopic examination with an "endocytoscopy" system.
Carcinoma, Squamous Cell↗
Hepatopulmonary syndrome increases the postoperative mortality rate following liver transplantation: a prospective study in 90 patients.
Hepatopulmonary syndrome (HPS) is a frequent pulmonary complication of patients with end-stage liver diseases. HPS is diagnosed by hypoxemia and pulmonary vascular dilatation and is an independent risk factor of mortality. Orthotopic liver transplantation (OLT) is the only factor that modifies the natural course of HPS. Once patients with HPS have been transplanted, their long-term survival rate is similar to transplanted patients without HPS. Consequently, HPS is an indication of OLT whatever the severity of hypoxemia. However, besides the favorable long-term survival of HPS patients with OLT, a high postoperative mortality (mostly within 6 months) has been suggested. The aim of our study was to analyze the incidence of HPS and postoperative outcome after OLT in 90 consecutive patients. All patients were prospectively included and had blood gas analysis to detect HPS. Patients with hypoxemia had contrast echocardiography to confirm HPS. Nine patients had HPS with a 50 </= PaO(2)</= 70 mmHg. Among them 3 (33%) died while the mortality rate was 9.2% in the group without HPS (7 over 76 patients). In the HPS patients who survived, the syndrome completely recovered within 6 months. In conclusion, our study shows a high postoperative mortality rate following OLT even though the preoperative PaO(2) was >50 mmHg in all HPS patients transplanted.
Adult↗
[Alcoholic and nonalcoholic steatohepatitis: the same disease! I. Diagnosis and mechanisms].
Alcoholic steatohepatitis includes steatosis, inflammatory changes and hepatocellular damage. In severe form, jaundice and hepatic failure persist for several weeks, while non severe alcoholic steatohepatitis may follow an insidious course towards cirrhosis. Except for alcohol consumption, nonalcoholic steatohepatitis shares histological features and pathogenic mechanisms with alcoholic steatohepatitis, and is associated to the development of cirrhosis over time. Thus, given the increasing epidemics of the metabolic syndrome in industrialized countries, it is likely that alcoholic cirrhosis has been overdiagnosed in the past years. Obesity, insulin resistance and the oxidative stress including iron-mediated oxidative stress are involved both in alcoholic and non-alcoholic steatohepatitis.
Alcohol Drinking↗
[Alcoholic and nonalcoholic steatohepatitis: the same disease! II. Management].
Both alcoholic and non-alcoholic steatohepatitis share common histological findings and the risk of developing cirrhosis. Liver biopsy is required for the diagnosis, and the aim of treatment is to prevent cirrhosis. In alcoholic steatohepatitis, abstinence from alcohol is associated to prednisone in a severe form, as defined by a Maddrey's score > 32. Due to common pathogenic mechanisms, we recommend that coexisting metabolic alterations that are commonly observed in non-alcoholic steatohepatitis should also be treated in alcoholics. Thus, weight reduction, physical exercise, improvement of insulin sensitivity and reduction of oxidative stress, all may be beneficial both in alcoholic and non-alcoholic steatohepatitis.
Alcohol Drinking↗
Low-dose oral microemulsion ciclosporin for severe, refractory ulcerative colitis.
BACKGROUND: The optimal modalities of treatment with oral microemulsion ciclosporin in patients with severe, steroid-refractory ulcerative colitis are uncertain. AIM: To assess the applicability, in terms of efficacy and tolerability, of a standard oral microemulsion ciclosporin treatment protocol targeting relatively low blood ciclosporin concentrations, in patients with severe, steroid-resistant ulcerative colitis. PATIENTS AND METHODS: Patients with a severe attack of ulcerative colitis and no satisfactory response to intravenous corticosteroids were started on oral microemulsion ciclosporin. Dosages were adapted according to a standard protocol, targeting a blood predose ciclosporin concentration (C0) of 100-200 ng/mL. Patients without a clinical response on day 8 were scheduled for colectomy. RESULTS: Sixteen patients were enrolled. A clinical response was observed in 14/16 (88%). The mean clinical activity index scores and concentrations of C-reactive protein on days 0, 4 and 8 were 11.8, 6.7 and 4.1, and 50.3, 19.3 and 9.7 mg/L respectively. The mean C0 (days 0-8) was 149 pg/mL. The mean creatinine clearance rates on days 0 and 8 were 88 and 96 mL/min. One patient had an acute elevation of transaminases that resulted in discontinuing ciclosporin. CONCLUSIONS: Even when dosed for a target C0 of 100-200 ng/mL, oral microemulsion ciclosporin for severe, steroid-refractory ulcerative colitis achieves an efficacy similar to that attained with higher, potentially more toxic levels. The oral route should replace intravenous treatment in this clinical setting.
Administration, Oral↗
Expression of NOX1, a superoxide-generating NADPH oxidase, in colon cancer and inflammatory bowel disease.
Reactive oxygen species (ROS) are at the centre of many physiological and pathological processes. NOX1, a ROS-producing NADPH oxidase, is highly expressed in the colon but its function in colonic physiology or pathology is still poorly understood. It has been suggested to play a role in host defence, but also in cell growth and possibly malignant transformation. In this study we characterized NOX1 expression in human colon samples derived from healthy control subjects and patients with colon cancer or inflammatory bowel disease (IBD). NOX1 mRNA expression was assessed by dot-blot hybridization, real-time PCR and in situ hybridization, using samples derived from surgical specimens from patients undergoing colon resection. In normal tissues, NOX1 expression was low in the ileum, intermediate in the right colon, and high in the left colon (p = 0.0056 right vs. left colon). NOX1 mRNA levels were not influenced by factors linked to colon tumourigenesis, such as age or sex. Moreover, there was no statistical difference in NOX1 expression between samples derived from adenomas, well differentiated or poorly differentiated colon adenocarcinomas. At a cellular level, NOX1 was highly expressed in colon epithelial cells, both within the crypts and on the luminal surface. In addition, a population of lymphocytes, particularly in the appendix, showed NOX1 expression. Lymphocytes in lesions of Crohn's disease and ulcerative colitis were also strongly positive for NOX1. In conclusion, NOX1 is an enzyme that is constitutively expressed in colon epithelium and is not associated with tumourigenesis. Its distribution in crypts and on the luminal surface, as well as its left-to-right gradient in the colon, suggests a role in host defence function. In addition to the known epithelial localization, we define lymphocytes as a novel site of NOX1 expression, where it may potentially be involved in the pathogenesis of inflammatory bowel diseases.
Adenocarcinoma↗
Diagnosis of a gastric mucosa-associated lymphoid tissue lymphoma by endoscopic ultrasonography-guided biopsies in a patient with a parotid gland localization.
We report the case of a 32-year-old man with a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma of the parotid gland associated with Sjögren syndrome. He underwent an upper endoscopy as part of the screening of a gastric localization which showed a diffuse non-specific gastritis. However, endoscopic ultrasonography (EUS) evidenced a focal wall thickening of the vertical portion of the smaller curvature. EUS-guided biopsies of this area disclosed a MALT lymphoma, whereas biopsies under endoscopy concluded to mild chronic gastritis. The search for Helicobacter pylori infection remained negative. Four months after treatment with anti-CD20 antibodies, EUS showed a diminution of the abnormal thickening of the second layer. Regression was confirmed histologically on new EUS-guided biopsies. MALT lymphoma is usually considered a localized disease; however, dissemination is probably more frequent than initially believed. Our case reflects the importance of a systematic screening for a gastric localization in patients with MALT lymphoma of the salivary glands. In this situation, association to autoimmune disease such as Sjögren syndrome is more likely to explain the gastric location than infection with H. pylori. Endoscopic ultrasonography has a major impact for the staging of gastric MALT lymphoma, but may also help diagnose focal infiltration by the disease.
Adult↗
Appendectomy and protection against ulcerative colitis.
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Appendectomy↗
New serum markers for the detection of severe acute pancreatitis in humans.
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Acute Disease↗
Acidosis modifies metabolic functions but does not affect vascular resistances in perfused rat livers.
BACKGROUND: Few data exist concerning the consequences of acidosis on intrahepatic vascular resistances and hepatic functions. METHODS: The consequences of pH and PCO2 changes on the intrahepatic vascular reactivity to norepinephrine (NE, 10(-9) to 3 x 10(-5) M) have been investigated in isolated rat livers perfused with solutions bubbled with 5, 10, or 15% CO2 and in solutions in which pH was decreased by replacing HCO3- with NaCl while maintaining a normal PCO2. Hepatic O2 consumption (VO2) and urea release were also measured during these experiments. RESULTS: The NE-induced increase of portal pressure did not change during hypercarbic and normocarbic acidosis. In contrast, the NE-induced increase of urea release was higher when the solution of perfusion was bubbled with 10 and 15% CO2, while during normocarbic acidosis the NE-induced increase of urea release did not change with pH. In the absence of NE, acidosis decreased hepatic VO2 and urea release but portal pressure was not modified by changing % CO2 or pH in the Krebs-Henseleit-bicarbonate solution. CONCLUSIONS: This study clearly shows that, in the liver, the consequences of acidosis are far more important on the metabolism (VO2 and urea release) than on the intrahepatic vascular resistance.
Acidosis↗