ABSTRACT
BACKGROUND AND PURPOSE: MR imaging and MR spectroscopy are increasingly being used to determine response to pharmacologic therapy. Hepatic encephalopathy (HE) is characterized by abnormal cerebral metabolites, yet the response to lactulose and other anti-HE measures is still primarily determined by using arbitrary categorical clinical rating scales, rather than MR spectroscopy. The purpose of this study was to determine whether MR spectroscopy could demonstrate relevant neurometabolic changes associated with lactulose therapy and thereby provide further support for the use of MR spectroscopy in clinical trials. METHODS: Ten control subjects and 23 patients with grades I to III HE were studied by proton MR spectroscopy with imaging parameters of 2000/26 (TR/TE). Metabolic ratios were calculated for myo-inositol (mI)/creatine (Cre), choline (Cho)/Cre, (glutamine + glutamate) (Glx)/Cre, N-acetylaspartate (NAA)/Cre, and (Cho + mI)/Glx. A time series design trial was used in which eight patients with HE were compared before and after lactulose therapy (60 mL by mouth three times per day). RESULTS: Relative to control subjects, HE was characterized by 43%, 64%, and 5% reductions, respectively, in mI/Cre, (Cho + mI)/Glx, and Cho/Cre. In comparison, Glx/Cre was increased by 75% and NAA/Cre was not changed. Therapy with lactulose was associated with increases of 29%, 37%, and 7%, respectively, in mI/Cre, (Cho + mI)/Glx, and Cho/Cre, as well as respective decreases of 15% and 42%, respectively, in Glx/Cre and HE grade. NAA/Cre did not change with lactulose therapy. CONCLUSION: MR spectroscopy detects neurometabolic changes associated with pharmacologic therapy for HE. The metabolic ratios ml/Cre and (Cho + mI)/Glx are the most sensitive measures of lactulose effect. These data support the expanded use of MR spectroscopy as an adjunctive technique in pharmaceutical development and clinical trials for HE.
Subject(s)
Brain/metabolism , Hepatic Encephalopathy/drug therapy , Hepatic Encephalopathy/metabolism , Lactulose/therapeutic use , Magnetic Resonance Spectroscopy , Administration, Oral , Adult , Choline/metabolism , Creatine/metabolism , Glutamic Acid/metabolism , Glutamine/metabolism , Hepatic Encephalopathy/diagnosis , Humans , Middle Aged , Reference ValuesSubject(s)
Anesthetics, Local/pharmacology , Benzalkonium Compounds/pharmacology , Benzocaine/pharmacology , Cetrimonium Compounds/pharmacology , Quaternary Ammonium Compounds/pharmacology , Stomach/physiopathology , Tetracaine/pharmacology , para-Aminobenzoates , 4-Aminobenzoic Acid/pharmacology , Drug Combinations/pharmacology , Endoscopy , Humans , Hydrogen-Ion Concentration , Saliva/drug effects , Stomach/drug effectsABSTRACT
The dependence of cells of the colonic epithelium upon lumenal short-chain fatty acids (SCFA) for some of their energy supply is well known. SCFA (mainly acetic, propionic, and n-butyric acids) comprise the predominant solutes in the aqueous phase of colonic contents and are produced by anaerobic bacterial fermentation of polysaccharides. Acetic acid is the principal fatty acid, but n-butyric acid is the preferred energy source for colonocytes, both in normal human colon and in colons of patients with ulcerative colitis. Four patients with diversion colitis, an inflammatory process in surgically excluded colon and rectum, were successfully treated by colonic instillation of a solution of mixed SCFA. This review examines the evidence that diversion colitis may be a new type of nutritional-deficiency syndrome based upon a local mucosal requirement for SCFA.
