Methodology of kinetic interaction studies in clinical pharmacology: an experimental contribution on diftalone and acetylsalicylic acid

The possible interaction of acetylsalicylic acid (ASA) and diftalone (DIF), a new anti-inflammatory drug, was studied in 6 volunteers. All subjects received each of the following three treatments: ASA 1 g, DIF 0.5 g, ASA 1 g plus DIF 0.5 g at 4-day intervals (stage 1 of the study). In stage II of the same study, each subject received ASA 1 g plus DIF 0.5 g in three different occasions 1 week apart; after a 7-day pre-treatment with either DIF 0.25 g b.i.d., or ASA 0.5 g b.i.d., or DIF 0.25 g b.i.d. plus ASA 0.5 g b.i.d. A total of four different comparisons were made. After pre-treatment with DIF, but not after pre-treatment with DIF plus ASA, the peak level of salicylate was significantly reduced by about 15%. No other evidence of interaction was found.     

Detection of hepatitis C virus with RNA polymerase chain reaction in fulminant hepatic failure

The role of hepatitis C virus (HCV) infection in fulminant hepatic failure is controversial. The frequency of serum HCV RNA positivity in previously reported patients with fulminant hepatic failure (FHF) of indeterminate cause ranged from 0 to 12% in the United States and Europe and from 43% to 59% in Asia. We assessed serum HCV RNA using polymerase chain reaction (PCR) and oligoprimers from the 5'UTR of the HCV genome in 26 consecutive patients with FHF. Another laboratory independently performed PCR on 21 of the serum samples using different oligoprimers from the 5'UTR and NS3 region of the HCV genome. Serum HCV RNA was detected in two of seven (28%) patients with hepatitis B, 9 of 15 (60%) with an indeterminate cause, and in none with hepatitis A (n = 2) or drug-induced hepatotoxicity (n = 2). HCV RNA PCR results were concordant between both laboratories in 17 of 21 (81%) of samples. In patients with an indeterminate cause, HCV RNA positivity was significantly associated with the transmission risk factor of low socioeconomic status and Hispanic ethnicity. Eighteen patients underwent liver transplantation (LT) and 15 (83%) survived. Among patients with FHF of indeterminate cause, recurrent or acquired HCV infection after transplantation occurred in three of five (60%) and one of four (25%) patients, respectively. Three of four (75%) patients with hepatitis C virus infection post-LT also developed histologic hepatitis. HCV appears to be the causative agent of a substantial number of cases of FHF classified as indeterminate in the Los Angeles area. Differences in patient populations or risk factors may explain the discordant incidences of HCV infection in FHF observed among different programs.     

Physiopathology of spontaneous extravasation of urine in the upper urinary tract. Apropos of 24 cases

Extravasation of urine was seen in 24 intravenous pyelograms taken for renal colic during the year 1973-74. A number of the patients presented with an acute abdomen. Extravasation took place of retained urine under pressure in the renal pelvis with leakage either around the clayces, from a fissure in the pelvis or even around the ureter. Extravasations of this type are in general rabsorbed without trace. In 5 cases, operation was necessary to drain a purulent collection which had developed in association with the extravasated urine.