Control of the mutagenicity of arylamines by protein kinases and phosphatases: II. Lack of response of rat liver N-acetyl transferases to phosphorylation modulators

OBJECTIVES: Endoscopic sphincterotomy has become a generally accepted method for extracting common bile duct stones in high risk or cholecystectomized patients. However, stone extraction is impossible by the usual methods in 5 to 10% of cases. The purpose of this study was to evaluate the effect of a recently developed solvent system in patients with large bile duct stones. METHODS: Forty four patients (15 men and 29 women, median age of years) underwent contact dissolution after unsuccessful Dormia extraction. Solvents were administered via a nasobiliary catheter in 41 patients following papillotomy and through a T-tube in 3 patients. Solvent mixtures (26 mM ethylene diamine tetraacetic acid, 40 mM sodium deoxycholate and 30% dimethyl sulfoxide in an alkaline aqueous solution; and a 70/30 dimethyl sulfoxide/methyl tert-butyl ether mixture) were infused continuously and alternatively for 2 hours. RESULTS: Bile duct stones disappeared in 13-24 hours of infusion in 11 patients. In 29 patients, a clear reduction in stone volume occurred, allowing complete endoscopic extraction of the fragments. In 4 patients, the size of the stone did not change. Only mild and transient side-effects including abdominal pain (68%), nausea (72%), vomiting (52%), diarrhea and sleepiness (50%) were observed. CONCLUSION: Direct dissolution therapy could be an effective method for the non-surgical management of large bile duct stones in selected patients when intra- or extracorporeal lithotripsy is unsuccessful.     

Signed rank statistics for coherent predictions

A generalization of Wilcoxon's signed rank test is proposed for testing a dose-response relationship with one or more outcomes. The test is useful in matched observational studies or in nonrandomized experiments that use dose-response relationships and predictions about multiple outcomes in an effort to distinguish actual treatment effects from hidden biases. A sensitivity analysis indicating whether a dose-response relationship or multiple predictions are confirmed with sufficient strength to reduce sensitivity to hidden bias is performed. Together, the test and the sensitivity analysis help to quantify the degree to which a coherent pattern of associations is present or absent, and the degree to which this strengthens or fails to strengthen evidence of cause and effect. Formal properties of tests of this kind are examined. The form of the optimal test is determined, though this test is not usable because it depends upon the values of the unknown parameters under study. Also examined are the conditions under which the proposed test resembles the optimal test, as well as the impact of various violations of those conditions on power. An example involving matched pairs exposed to varying doses of cadmium is considered in detail.     

Evaluation of the dizzy patient

This discussion has focused primarily on the history and physical examination of the patient with dizziness which, in fact, are the two most important elements in the evaluation process. To perform the examination expeditiously and completely, a broad differential diagnosis of dizziness must be kept in mind. The clinician should also keep in mind two basic objectives: first, to identify serious pathology (e.g., central nervous system lesion, brainstem ischemia, cardiac arrhythmia); and second, to recognize diseases that can be specifically treated, such as an endocrine abnormality, middle ear infection, Meniere's disease, or a drug reaction. Reassurance and/or vestibular rehabilitation are the mainstays of therapy for the patients not falling into the above two categories.