The effects of the addition of clonidine to diuretics on the mobilization of ascites in the short term (diuretic response and requirement of diuretics) and the long term (readmissions for tense ascites and requirement of diuretics) were examined in patients with cirrhosis and with increased sympathetic nervous system (SNS) activity. We also studied neurohormonal, hemodynamic effects and side effects of clonidine and diuretics. Patients were randomized to receive placebo (group1, n ‫؍‬ 32) or clonidine (0.075 mg) twice daily (group 2, n ‫؍‬ 32) for 3 months. After 8 days and for 10 days duration, spironolactone (200 mg/day) was added in both groups. After this period, the dosages of diuretics were individually increased until diuretic response. Responding patients were discharged and followed at the outpatient clinic. During the first hospitalization, the time needed for diuretic response was shorter in group 2 than in group 1. The mean requirement for diuretics was significantly higher in group 1 than in group 2, and the diuretic complications (hyperkalemia and renal impairment) were significantly lower in group 2. Clonidine induced a permanent decrease in SNS activity and delayed decrease in renin/aldosterone levels. During the follow-up, the time to the first readmission for tense ascites was shorter in group 1 than in group 2. Readmissions related to tense ascites or diuretic complications were significantly lower in group 2. The mean requirement for diuretics was significantly higher in group 1 than in group 2. In conclusion, the additional administration of clonidine to diuretics induced an earlier diuretic response associated with fewer diuretic requirements and complications. T he mechanisms leading to renal sodium retention in cirrhosis are not fully understood. Splanchnic arterial vasodilatation associated with portal hypertension induces a reduction in effective blood volume and permanent activation of antinatriuretic and vasoconstrictive mechanisms (stimulation of renin/aldosterone and sympathetic systems, vasopressin secretion). 1 The sympathetic nervous system (SNS) contributes to renal hypoperfusion and sodium retention. The activated SNS stimulates renal ␣ 1 -adrenoreceptors and causes decreases in renal blood flow and glomerular filtration rate. Additionally, norepinephrine increases proximal tubular reabsorption of sodium and enhances renin, aldosterone, and vasopressin secretions. 2, 3 We recently showed that in patients with cirrhosis and ascites, the marked activation of SNS and renin/aldosterone axis reduced diuretic response. 4 Consequently, inhibitions of SNS activity and renin/aldosterone system would improve diuretic response.Clonidine, a centrally acting ␣ 2 -agonist, has been shown to offer sympatholytic activity in patients with arterial hypertension or cirrhosis. [5][6][7][8] Co-administration of clonidine and spironolactone has been shown to increase natriuresis and body weight loss more efficiently than spironolactone alone in patients with cirrhosis and ascites and activated SNS i...

Background: Serum concentrations of monoglycosylated isoforms of transferrin are increased by chronic ethanol intake. We investigated transferrin glycosylation in patients with cancer, in which aberrant glycosylation is also induced. Methods: We used a P/ACE 5000 series capillary zone electrophoresis (CZE) apparatus and a CZE carbohydrate-deficient transferrin reagent set to study 200 cancer patients who consumed alcohol moderately and 33 who were alcohol abusers; we then compared these patients with 56 healthy teetotalers, 89 moderate, and 112 excessive alcohol drinkers without known malignancies. Transferrin isoforms were identified by immunosubtraction with anti-human transferrin polyclonal antibody. Results: Seven peaks, P0 -P6, were visualized and completely or partly immunosubtracted when CZE separation was performed at pH 8.5. P0 was present in 95% of alcohol abusers with or without cancer. P3 was significantly higher in cancer patients and was only partly immunosubtracted as trisialotransferrin in all groups. The comigrating analyte was not altered by papain, precipitation by ethanol, or extraction by organic solvents, but was sensitive to acid hydrolysis, suggesting a polysaccharide structure. When isolated at pH 8.25, this analyte was higher in cancer patients. ROC curve analysis identified localized malignant neoplasia at P3 values above 5.8% of total transferrin (sensitivity, 0.78;

No abstract

No abstract

No abstract