What is already known about this subject • The occurrence of idiosyncratic drug hepatotoxicity is a major problem in all phases of clinical drug development and the leading cause of postmarketing warnings and withdrawals. • Physical exercise can result in transient elevations of liver function tests. • There is no consensus in the literature on which forms of exercise may cause changes in liver function tests and to what extent. What this study adds • Weightlifting results in profound increases in liver function tests in healthy men used to moderate physical activity, not including weightlifting. • Liver function tests are significantly increased for at least 7 days after weightlifting. • It is important to impose relevant restrictions on heavy muscular exercise prior to and during clinical studies. Aim To investigate the effect of intensive muscular exercise (weightlifting) on clinical chemistry parameters reflecting liver function in healthy men. Methods Fifteen healthy men, used to moderate physical activity not including weightlifting, performed an 1 h long weightlifting programme. Blood was sampled for clinical chemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LD), gamma‐glutamyl transferase (γGT), alkaline phosphatase (ALP), bilirubin, creatine kinase (CK) and myoglobin] at repeated intervals during 7 days postexercise and at a follow‐up examination 10–12 days postexercise. Results Five out of eight studied clinical chemistry parameters (AST, ALT, LD, CK and myoglobin) increased significantly after exercise (P < 0.01) and remained increased for at least 7 days postexercise. Bilirubin, γGT and ALP remained within the normal range. Conclusion The liver function parameters, AST and ALT, were significantly increased for at least 7 days after the exercise. In addition, LD and, in particular, CK and myoglobin showed highly elevated levels. These findings highlight the importance of imposing restrictions on weightlifting prior to and during clinical studies. Intensive muscular exercise, e.g. weightlifting, should also be considered as a cause of asymptomatic elevations of liver function tests in daily clinical practice.

The accurate diagnosis of submucosal gastric lesions is difficult. In an attempt to study this problem, the endoscopic records for 8 consecutive years (July 1976-June 1984) were scanned with the help of a computer-based registration of the endoscopic findings. The examinations were identified in which the endoscopic diagnosis indicated the presence of a submucosal tumor. Fifty-four such patients were found in 15,104 routine examinations, giving an incidence of 0.36%. Six patients were lost to follow-up, so the study is based on 48 patients. The most common reason these patients underwent endoscopy was abdominal pain. Five patient groups were identified: (a) nine patients were correctly diagnosed as having gastric wall neoplasia at the initial endoscopy + biopsy; (b) in an additional 13 patients, the suspected gastric wall neoplasia was verified by further nonoperative diagnostic procedures; (c) five patients were found to have benign non-neoplastic gastric disease; (d) five patients had extra-gastric disease that pressed against the gastric wall; (e) in 14 patients a further work-up indicated that the initial endoscopy was false-positive. These five groups were confirmed by additional diagnostic procedures (including laparotomy) and a follow-up time of more than 5 years or autopsy. Two patients refused further examinations and died shortly afterward. No autopsies were performed. Based on our data, it would seem that in the vast majority of patients the suspicion of a submucosal gastric lesion at endoscopy indicates the presence of a serious condition.

The cytochrome P450 3A4 enzyme and the ABC-transporters may affect the first-pass extraction and bioavailability of drugs and metabolites. Conflicting reports can be found in the literature on the expression levels of efflux transporters in human intestine and how they vary along the intestine. The relative levels of mRNA and protein of CYP3A4 and the ABC tranporters Pgp (ABCB1), MRP1 (ABCC1), and MRP2 (ABCC2) were determined using RT-PCR and Western blot for human intestinal tissues (n = 14) from jejunum, ileum and colon. The expression of mRNA for CYP3A4, Pgp, and MRP2 was highest in jejunum and decreased toward more distal regions, whereas MRP1 was equally distributed in all intestinal regions. For CYP3A4, a more significant correlation could be established between mRNA and protein expression than for the ABC transporters. The samples showed considerable interindividual variability, especially at the protein level. The apically located Pgp and MRP2 showed a similar expression pattern along the human intestine as for CYP3A4. The gene expression of MRP1 exhibited a more uniform distribution.