Lanreotide Autogel in the Treatment of Idiopathic Refractory Diarrhea: Results of an Exploratory, Controlled, Before and After, Open-label, Multicenter, Prospective Clinical Trial.

PURPOSE: Chronic idiopathic diarrhea is the passage of loose stools >3 times daily, or a stool weight >200 g/d, persisting for >4 weeks without clear clinical cause. Patients refractory to standard anti-diarrhetics have limited treatment options. Somatostatin analogues have the ability to reduce gastrointestinal secretions and motility. This study evaluated the efficacy and safety of lanreotide Autogel(*) 120 mg in chronic idiopathic diarrhea. METHODS: Other anti-diarrhetics were not allowed during the study and were stopped at screening. Patients received lanreotide Autogel 120 mg at baseline and day 28. Stool frequency and consistency (Bristol Stool Scale) were recorded; quality of life (QoL) was assessed using the 36-item Short Form Health Survey and irritable bowel syndrome QoL questionnaires; adverse events were monitored. The primary outcome was the proportion of patients with a reduction of ≥50% or normalization to a mean of ≤3 stools/d at day 28. FINDINGS: Thirty-three patients with >3 stools/d at baseline were included; mean (SD) age was 55.2 (16.4) years. Fourteen patients (42.4%) had a response to lanreotide Autogel at day 28 and 17 (51.5%) at day 56. Mean (SD) number of stools decreased significantly from 5.7 (2.2) at baseline to 3.7 (2.2) at day 56 overall (n = 32; P < 0.001). Significant and clinically meaningful improvements in disease-specific QoL were found in the overall populations. No new safety signals emerged. IMPLICATIONS: Lanreotide Autogel 120 mg decreased symptoms in these patients with chronic idiopathic refractory diarrhea, and meaningfully improved QoL. These finding have to be confirmed in further clinical trials. ClinicalTrials.gov IDENTIFICATION: NCT00891371; Eudract CT 2009-009356-20.

Effects of clonidine on diuretic response in ascitic patients with cirrhosis and activation of sympathetic nervous system.

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 (group 1, 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.

Comparative pilot study of repeated large volume paracentesis vs the combination on clonidine-spironolactone in the treatment of cirrhosis-associated refractory ascites.

OBJECTIVES: To study the usefulness of the combination of clonidine--spironolactone in refractory ascites. METHODS: Twenty cirrhotic patients with refractory ascites were randomly assigned to receive repeated large volume paracentesis plus intravenous albumin (group 1), or a combination of clonidine (0.075 mg twice daily) and spironolactone (200 to 400 mg daily) (group 2). RESULTS: During the first hospitalisation,, the mean weight loss in group 1 was higher than in group 2 (12.4 +/- 3.2 versus 4.3 +/- 1.1 kg, P < or = 0.01). Mean stay in hospital was shorter in group 2 (20 +/- 1.5 versus 10 +/- 2.8 days; P < or = 0.01). Paracentesis did not induce changes in neuro-hormonal measurements. Oppositely, clonidine induced a decreased sympathetic activity, an increased glomerular filtration rate and a delayed reduction of the renin-aldosterone levels. During the follow-up in group 1, the number of rehospitalisations for ascites was higher than in group 2 (37 versus 3; P < or = 0.01), and the mean time to the first readmission was shorter (10 +/- 2.7 versus 23.7 +/- 5.6 days; P < or = 0.01). The total duration spent in hospital were similar in both groups. CONCLUSION: Paracentesis is more effective for short-term treatment of ascites but clonidine-spironolactone association might provide better long-term control.

Analyte comigrating with trisialotransferrin during capillary zone electrophoresis of sera from patients with cancer.

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; specificity, 0.87), regardless of alcohol consumption. Disseminated cancers were better differentiated above 8% (sensitivity, 0.94; specificity, 0.96). CONCLUSIONS: Malignant neoplasia, unlike excessive ethanol intake, did not alter the addition of two N-glycans to transferrin. A peak comigrating with trisialotransferrin had characteristics of a polysaccharide in all adults and was increased in sera of patients with cancer.