SUMMARY Samples of serum, bile, and urine were collected simultaneously from patients with cholestasis of varying aetiology and from patients with cirrhosis; their bile acid composition was determined by gas/liquid chromatography and mass spectrometry In cholestasis, the patterns in all three body fluids differed consistently and strikingly. In serum, cholic acid was the major bile acid and most bile acids (> 93 %) were unsulphated, whereas, in urine, chenodeoxycholic was the major bile acid, and the majority of bile acids (> 60 %) were sulphated. Secondary bile acids were virtually absent in bile, serum, and urine. The total amount of bile acids excreted for 24 hours correlated highly with the concentration of serum bile acids; in patients with complete obstruction, urinary excretion averaged 71 6 mg/24 h. In cirrhotic patients, serum bile acids were less raised, and chenodeoxycholic acid was the predominant acid. In healthy controls, serum bile acids were consistently richer in chenodeoxycholic acid than biliary bile acids, and no bile acids were present in urine. No unusual monohydroxy bile acids were present in patients with primary biliary cirrhosis, but, in several patients, there was a considerable amount of hyocholic acid present in the urinary bile acids. The analyses of individual bile acids in serum and urine did not appear to provide helpful information in the differential diagnosis of cholestasis. Thus, in cholestasis, conjugation of chenodeoxycholic acid with sulphate becomes a major biochemical pathway, urine becomes a major route of bile acid excretion, and abnormal bile acids are formed.

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A small double-blind controlled trial to evaluate the short-term effects of D-penicillamine therapy was carried out in 24 patients with primary biliary cirrhosis (PBC). The daily dose of D-penicillamine was increased monthly by 250 mg until a total of 1 g daily was reached. Two out of 11 patients (18%) were withdrawn because of side-effects, as also were 4 out of 13 (31%) patients receiving the placebo. Transient improvement in symptoms was observed in 4of 11 patients on D-penicillamine, but also in 5 of 13 patients from the placebo group. The proportion of patients showing a fall in serum IgM, IgG and hepatic copper was significantly larger for the D-penicillamine group than for the placebo group. No improvement in liver tests was observed, but the progression of inflammatory periportal liver cell destruction (piecemeal necrosis) was retarded in patients on D-penicillamine @=0.02). Data analysis within the Dpenicillamine group showed that lowering the dose of D-penicillamine to 500 mg daily abolished the effect on the serum immunoglobulins and hepatic copper. The beneficial effect of D-penicillamine therapy appears to be small and doserelated; side effects should not prevent its use, provided the drug is introduced slowly.

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During the last four years, our research has been focussed on prediction criteria for IVF after a Short Course of psychotherapy. Our study can be divided in two phases: In an earlier phase (up to 1990), prediction criteria were derived from "expert" rating, whereas in a later phase (from 1990 onwards) they were derived by self-rating of the patients. The predictions refer to changes in the patients' behaviour, affective state, mood and attitude (acronym: BAMA) towards their infertility. Our work is based on the hypothesis, that a perceivable change in BAMA and in how the patients relate to their wanting a child, represents the solution of the problem, which facilitates the consequential events of either pregnancy or acceptance of childlessness or else adoption. As a rule, the absence of such a change entails none of the consequential events. - We report on and discuss the results of the earlier, as well as the later phase and finally compare them as to how well they correlate with prediction and consequences. A marked correlation could be found between changes in BAMA and the occurrence of pregnancy or acceptance of childlessness in both phases of our study. Comparing the two phases (expert- vs. self-rating) on the accuracy of prediction, we could find almost identical results. Because of the easier and more economical application of self-rating we decided to continue with this method and to refine it for further research.

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