Stanton G. Axline

Computer-based consultations in clinical therapeutics: Explanation and rule acquisition capabilities of the MYCIN system☆

Abstract This report describes progress in the development of an interactive computer program, termed MYCIN, that uses the clinical decision criteria of experts to advise physicans who request advice regarding selection of appropriate antimicrobial therapy for hospital patients with bacterial infections. Since patients with infectious diseases often require therapy before complete information about the organism becomes available, infectious disease experts have identified clinical and historical criteria that aid in the early selection of antimicrobial therapy. MYCIN gives advice in this area by means of three subprograms: (1) A Consultation System that uses information provided by the physician, together with its own knowledge base, to choose an appropriate drug or combination of drugs; (2) An Explanation System that understands simple English questions and answers them in order to justify its decisions or instruct the user; and (3) A Rule Acquisition System that acquires decision criteria during interactions with an expert and codes them for use during future consultation sessions. A variety of human engineering capabilities have been included to heighten the programs acceptability to the physicians who will use it. Early experience indicates that a sample knowledge base of 200 decision criteria can be used by MYCIN to give appropriate advice for many patients with bacteremia. The system will be made available for evaluation in the clinical setting after its reliability has been shown to approach that of infectious disease experts.

An Artificial Intelligence program to advise physicians regarding antimicrobial therapy

Abstract An antimicrobial therapy consultation system has been developed which utilizes a flexible representation of knowledge. The novel design facilitates interactive advice-giving sessions with physicians. An ability to display reasons for making decisions at the request of the user permits the program to serve a tutorial as well as consultative role. The feasibility of the judgmental rule approach which the program uses has been demonstrated with a limited knowledge base of approximately 100 rules. Its ultimate success as a clinically useful tool depends upon acquisition of additional rules and thus upon co-operation of infectious disease experts willing to improve the programs knowledge base. The techniques for acquisition, representation, and utilization of knowledge, plus considerations of natural language processing, draw upon and contribute to current Artificial Intelligence research.

Amikacin Therapy: Use Against Infections Caused by Gentamicin- and Tobramycin-Resistant Organisms

Amikacin sulfate was used in 24 treatment courses for 25 serious infections caused by aerobic or facultative anaerobic Gram-negative organisms resistant to numerous drugs. Sites of infection included urinary tract (11 cases), pleuropulmonary (6 cases), primary bacteremia (5 cases), and miscellaneous (3 cases). Serratia marcescens and Pseudomonas sp accounted for 73% of the isolates. The mean minimal inhibitory concentration (MIC) of these organisms to amikacin was 3.6 microgram/ml; to gentamicin, 39 microgram/ml; and to tobramycin, 32 microgram/ml. The mean peak serum concentration of the drug was 20.8 microgram/ml. Eleven patients were critically ill at the onset of therapy, and seven patients were bacteremic. The overall favorable response rate was 80%. The most serious side effect was ototoxicity, which occurred in three of 15 patients examined by serial audiometry.

Aryl hydrocarbon hydroxylase induction in mouse peritoneal macrophages and blood-derived human macrophages.

Summary Macrophages of human and mouse origins were shown to contain inducible aryl hydrocarbon hydroxylase activity. Mononuclear phagocytic cells derived from circulating blood monocytes of healthy human donors and peritoneal macrophages from untreated C57 B1/6 mice exhibited low levels of enzyme activity. For mice, aryl hydrocarbon hydroxylase specific activity of freshly explanted macrophages was 1/70th the enzyme activity found in liver. Aryl hydrocarbon hydroxylase activity for both human and mouse macrophages maintained in vitro in the presence of benzanthracene exceeded by 2-3 fold the enzyme specific activity of cells cultivated in the absence of inducer.

Drug Concentrations and Overdosage

To the Editor:— Studies on the clinical pharmacology of drugs in newborn infants have uncovered a problem of overdosage which may be more common than is generally appreciated. Several medicaments are available only in a limited number of highly concentrated formulations. The requirements of premature and full-term newborn infants for very small total dosages necessitate very careful measurement of minute quantities of drug. Overdosage can easily occur. Specifically, kanamycin sulfate is available in only two formulations for injection, containing, respectively, 250 and 333 mg/ml. The dosage of this agent for newborn infants is approximately 8 mg per kilogram of body weight every 12 hours. The injection mass for a premature infant weighing 1 kg (2.204 lb) should therefore consist of 0.024 ml of the 333 mg/ml formulation, or 0.032 ml of the 250 mg/ml formulation. Clearly, these quantities are impossible to measure accurately in a syringe unless a prior dilution