Tranexamic acid through intravenous,intramuscular and oral routes: an individual participant data meta‐analysis of pharmacokinetic studies in healthy volunteers

Tranexamic acid (TXA) is an antifibrinolytic drug that reduces surgical blood loss and death due to bleeding after trauma and post‐partum haemorrhage. One key issue for treatment success is early administration. While usually given intravenously, oral and intramuscular use would be useful in specific circumstances. Therefore, an understanding of TXA pharmacokinetics when given via different routes is valuable. The aim of this study was to perform an individual participant data meta‐analysis of pharmacokinetic studies with TXA given to healthy volunteers via different routes. We searched the following databases: PubMed, Web of Science, Wiley Online Library, Elsevier Science Direct and J‐STAGE. Individual subject data were extracted when available, otherwise arithmetic means were used. A population pharmacokinetic model was developed using nonlinear mixed effect modelling. Seven studies were included in the analysis with data from 10 patients for the IV route, six patients for the IM route and 114 patients for the oral route. The pharmacokinetics was ascribed to a two‐compartment model, and the main covariate was allometrically scaled bodyweight. Oral and IM bioavailabilities were 46 and 105%, respectively. For a 70 kg bodyweight, the population estimates were 7.6 L/h for clearance, 17.9 L for the volume of the central compartment, 2.5 L/h for the diffusional clearance and 16.6 L for the peripheral volume of distribution. Larger well‐designed studies are needed to describe the pharmacokinetics of TXA when given IM or as an oral solution before these can be recommended as alternatives to IV.     

One-stage hepatectomy in the dog

This report describes a technique for total hepatectomy in the dog. The procedure maintains the integrity of the gastrointestinal tract and the pancreas in the normothermic, anesthetized animal. The technique involves (i) a mesentericocaval shunt, (ii) a temporary external bypass between the femoral and jugular veins, and (iii) a permanent internal bypass between the abdominal and thoracic inferior vena cava through the tendinous area of the diaphragm. This 60- to 70-min procedure yields a preparation useful for short-term metabolic studies in nonhepatic tissues.     

Implications of the revised surveillance definition: AIDS among New York City drug users.

The Centers for Disease Control (CDC) has proposed revising the AIDS surveillance definition to include any HIV-seropositive person with a CD4 cell count of less than 200 cells per microliter. Based on a study of persons receiving treatment for HIV infection, this new definition would lead to an estimated 50% increase in the number of persons recognized as living with AIDS. Among 440 HIV-seropositive research subjects recruited from drug treatment programs and through street outreach in New York City, 59 met this definition, yet only 25% of those had been reported to the New York City AIDS registry. The new definition, if combined with HIV and T-cell testing at drug treatment and street outreach programs, could thus yield very large increases in the number of injecting drug users meeting the new surveillance definition of AIDS.     

Hepatobiliary scintigraphy in a patient with bilhemia

A 4-year-old child referred for acute jaundice following percutaneous needle biopsy of the liver underwent hepatobiliary scintigraphy. Although all conventional liver tests suggested preservation of hepatocyte function, the tracer uptake in the liver appeared dramatically reduced at scintigraphy and the blood pool activity did not decrease significantly until the end of the study. Visualization of the bile ducts indicated, however, that the tracer was taken up by the hepatocyte and further excreted into the biliary tree. There was no tracer pooling in the biliary tree although no bowel activity was observed, even on delayed images. The association of persistent blood pool activity, bile duct visualization without tracer pooling, and nonvisualization of the bowel was caused by a continuous recirculation of the tracer from the biliary tree into the bloodstream. The presence of a biliovenous fistula was further proven by percutaneous transhepatic cholangiography performed 24 h later. Since 1975, only 16 cases of bilhemia have been reported. To the best of our knowledge the scintigraphic pattern of this rare but lifethreatening complication has not previously been reported.     

Mechanism and prediction of nonspecific toxicity to fish using bioconcentration characteristics

A basic theory of nonspecific toxicity has been developed using bioconcentration as a basis and applying kinetic relationships developed in previous work. This approach has involved calculation of the critical volume fraction and critical concentration in lipid tissue of fish for a variety of organic compounds at the lethal level. Corrections to previous data sets for time period of exposure and inclusion of biodegradable compounds did not make a significant improvement in the values obtained. A new data base with compounds containing a wide range of Kow values gave results for critical volume and concentration similar to previous work. The influence of experimental procedures and methods for data development are considered. The basic theoretical derivation developed was found to provide a basis for predicting the approximate nonspecific toxicity of nondegradable lipophilic organic compounds at different exposure time periods. This requires a knowledge of the Kow value and the clearance rate constant (k2) which can be calculated from the Kow value.     

Intrauterine cerebral infarcts and bilateral frontal cortical leukomalacia following chronic maternal inhalation of carburetor cleaning fluid during pregnancy.

Little is known about the effect of inhalation of methanol and other solvents on the pregnancy and the growth of the fetus. We report a preterm male infant who developed cerebral infarcts in utero, leading to large areas of bilateral frontal cortical leukomalacia following chronic maternal inhalation of carburetor-cleaning fluid during pregnancy. The infant presented with acute fetal distress with significant metabolic acidosis at birth. Initial hypotonia was followed by generalized hypertonicity. This infant did not exhibit typical facial features of fetal alcohol syndrome.