ABSTRACT
BACKGROUND: We report two cases of antidepressant induced cholestasis. CASE REPORTS: We describe the first reported case of acute cholestasis due to citalopram (selective serotonin reuptake inhibitor) occurring in a patient who also experienced obstetric cholestasis in association with each of three pregnancies; in a second patient cholestasis developed due to dothiepin (tricyclic antidepressant), and six years later due to paroxetine. In both cases liver biopsies showed features of a "pure" cholestasis with total resolution within 1-6 months after withdrawal of the causative drug. Immunostaining for the canalicular transporter, multidrug resistant protein 2 (MRP2), responsible for biliary secretion of several organic anions including bilirubin glucuronides, showed sustained expression in both biopsies as well as relocalisation with appearance of strong staining of the basolateral membrane of the hepatocyte. This finding has also not been reported previously. CONCLUSIONS: We postulate that intracellular redistribution of MRP2 may reflect an adaptive compensatory mechanism which helps in the elimination of the drug or its cholestatic metabolites from the hepatocyte back to the sinusoidal space and subsequent excretion in urine. Changes seen in these two patients differ from findings previously reported in rats where downregulation of mrp2 occurs in response to experimentally induced cholestasis. We speculate that the rat is more advanced than humans in its ability to downregulate canalicular transporter expression as protection against progressive intrahepatic cholestasis.
Subject(s)
Antidepressive Agents/adverse effects , Cholestasis/chemically induced , Mitochondrial Proteins , Ribosomal Proteins/metabolism , Saccharomyces cerevisiae Proteins , Acute Disease , Adult , Antidepressive Agents, Second-Generation/adverse effects , Antidepressive Agents, Tricyclic/adverse effects , Biopsy , Cholestasis/metabolism , Cholestasis/pathology , Citalopram/adverse effects , Dothiepin/adverse effects , Female , Humans , Immunohistochemistry , Liver/pathology , Male , Middle Aged , Paroxetine/adverse effects , Pregnancy , Pregnancy Complications/chemically induced , Pregnancy Complications/metabolism , Pregnancy Complications/pathologySubject(s)
Carcinoma, Squamous Cell , Esophageal Neoplasms , Lymph Nodes/pathology , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophageal Neoplasms/therapy , Humans , Lymphatic Metastasis , Neoplasm Staging/methods , Prognosis , Retrospective Studies , Survival RateABSTRACT
BACKGROUND AND STUDY AIMS: A clean colon is essential for an efficient examination. The aim of this study was to compare a novel low-dose, low volume triple regimen with Fleet Phospho-soda. METHODS: A blinded, experienced colonoscopist examined 132 consecutive patients randomly allocated to receive either a triple regimen consisting of senna syrup (sennoside B), Picolax (sodium picosulphate), and Klean Prep (polyethylene glycol 3350), or Fleet Phospho-soda (sodium dihydrogen phosphate and disodium phosphate dodecahydrate). The colonoscopist recorded cleanliness according to a scoring system (1-very clean to 4-solid stools), and time taken to reach the caecum. RESULTS: In the triple regimen group (n = 81), 73% scored 1 or 2 compared with 57% in the Fleet Phospho-soda group (n = 51, p = 0.037 Mann-Whitney U-test). Examination to caecum was achieved in 95% of the triple regimen group and 89% of the Fleet Phospho-soda group. Among those examined as far as the caecum, the time to reach the caecum was 11 minutes (range 5-50) in the triple regimen group compared with 16 minutes (range 5-65) in the Fleet Phospho-soda group (p = 0.08, Mann-Whitney U-test). Patient tolerability was not assessed in this study. CONCLUSIONS: This novel triple regimen produces a cleaner colon than Fleet Phospho-soda, is associated with a trend towards a quicker and more efficient colonic examination, and is also 30% cheaper per patient.
