Our objective was to identify microRNA (miRNA) biomarkers of drug-induced liver and kidney injury by profiling the circulating miRNome in patients with acetaminophen overdose. Plasma miRNAs were quantified in age- and sex-matched overdose patients with (N = 27) and without (N = 27) organ injury (APAP-TOX and APAP-no TOX, respectively). Classifier miRNAs were tested in a separate cohort (N = 81). miRNA specificity was determined in non-acetaminophen liver injury and murine models. Sensitivity was tested by stratification of patients at hospital presentation (N = 67). From 1809 miRNAs, 75 were 3-fold or more increased and 46 were 3-fold or more decreased with APAP-TOX. A 16 miRNA classifier model accurately diagnosed APAP-TOX in the test cohort. In humans, the miRNAs with the largest increase (miR-122-5p, miR-885-5p, miR-151a-3p) and the highest rank in the classifier model (miR-382-5p) accurately reported non-acetaminophen liver injury and were unaffected by kidney injury. miR-122-5p was more sensitive than ALT for reporting liver injury at hospital presentation, especially combined with miR-483-3p. A miRNA panel was associated with human kidney dysfunction. In mice, miR-122-5p, miR-151a-3p and miR-382-5p specifically reported APAP toxicity - being unaffected by drug-induced kidney injury. Profiling of acetaminophen toxicity identified multiple miRNAs that report acute liver injury and potential biomarkers of drug-induced kidney injury.
SUMMARY A safe non-invasive technique for the measurement of gastric volume by real-time ultrasound is described. The application of this technique to the measurement of the emptying of liquid from the stomach is outlined. Gastric emptying of liquid was found to be log-linear, the mean half-life of emptying in 10 volunteers being 22.0±2.5 min. Ultrasound measurement of gastric emptying provides an opportunity to study the effects of drugs and disease on gastric motor function in man.The rate of gastric emptying of orally administered drugs is recognised to be of great importance in controlling both the rate of drug absorption, and the peak plasma concentrations that result. The factors that alter gastric emptying rate will in turn influence these parameters.' Current techniques for the direct assessment of gastric emptying involve the swallowing of orogastric tubes or exposure of the subject to ionising radiation.2 There is thus a need for a non-invasive method for the measurement of gastric emptying which is safely repeatable in normal subjects. We have previously described the application of single beam ultrasound for the measurement of gastric contraction frequency.3 4 We have also outlined a simple but approximate method for the determination of stomach volumes by a hand-held real-time probe.5 Subsequently other workers have also reported the usefulness of real-time ultrasound in recording and measuring gastric contractions.6We now report the application of real-time ultrasound to enable the accurate and rapid direct measurement of the volume of liquid in the stomach, and the use of this technique to measure the gastric emptying rate of a liquid meal.Method PRINCIPLE Short pulses of ultrasound will pass through a liquid but are partially reflected by solid interfaces, producing echoes. The time taken for an echo to return to a sensor (transducer) on the skin is determined by
The reporting rates of adverse drug reactions in the Northern Region have been examined with respect to source (hospital or general practice) and district of origin for the 3 years 1986‐88. Mean annual reporting rates, corrected for population, or clinical activity, varied approximately 4‐fold in general practice (0.066 to 0.257 reports per 1000 resident population) and more than 12‐fold in hospitals (0.14 to 1.77 reports per 1000 deaths and discharges). There was no correlation between hospital and general practice reporting rates in the same health district. Overall more reports were received from general practice (1606) than hospitals (1000), although proportionally more reports of serious adverse reactions originated from hospitals. The reasons for these differences are unclear.
Paracetamol has been used as an analgesic and antipyretic for many years, with toxicity first noted in the 1960s. Since then the incidence of poisoning has increased, and paracetamol is now the most common drug in self-poisoning, with a high rate of morbidity and mortality. The use, abuse and ways of reducing paracetamol toxicity are reviewed, but in view of the potential for harm, serious consideration should be given to changing the legal status of paracetamol, possibly to a prescription-only medicine.
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