Michael S. Phillips

Refinement of diagnostic assays for a probable causal mutation for porcine and human malignant hyperthermia

The substitutions of T for C1843 in the porcine ryanodine receptor (RYR1) gene, which deletes a HinPI restriction endonuclease site and creates a HgiAI site, and of T for C1840 in human RYR1, which deletes a RsaI site, lead to Cys for Arg substitutions in the ryanodine receptors and are probable causal mutations for malignant hyperthermia (MH). To improve the restriction endonuclease assay of these sites, thereby providing an accurate, reliable diagnosis for MH, introns flanking the exon containing the mutation were sequenced, permitting identification and PCR amplification of a 659-bp porcine gene sequence that contains both constant and variant HgiAI sites and a 922-bp human gene sequence that contains both constant and variant RsaI sites. As a result, these PCR-amplified sequences contain constant internal controls for the reliable differentiation by restriction endonuclease digestion of normal, heterozygous, and MH genotypes.

Psychiatric patients who discharge themselves against medical advice.

Hospital treatment staff are constantly faced with the problem of psychiatric patients who discharge themselves against medical advice before their treatment is completed. A total of 50 patients who signed themselves out of the 9th floor service of the Clarke Institute of Psychiatry, over a two year period, were analyzed. When compared with a random sample of patients who remained for the duration of their treatment, the authors found the A MA patients to have the following characteristics: The patient is likely to be a young male, admitted as an emergency, remain in hospital for three days or less and have a diagnosis of personality disorder or schizophrenia. The authors conclude with a number of recommendations to assist in dealing with the problem.

The Genetic and Physiological Basis of Malignant Hyperthermia

A goal of research in basic biological science is to develop understanding of normal processes that will be relevant to the understanding of disease processes. This goal has been realized to a large extent for the inherited neuromuscular abnormality malignant hyperthermia (MH), which is manifested most commonly in humans as anesthetic-induced muscle contracture, accompanied by high fever. The syndrome became widely recognized in the mid-1950s, following the introduction of halothane and succinylcholine as the most widely used combination of anesthetic and muscle relaxant. In certain families, the combination of inhalational anesthetics with a depolarizing muscle relaxant was fatal to individuals genetically predisposed to MH.1

PATIENTS WHO REOFFEND WHILE ON WARRANTS OF THE LIEUTENANT-GOVERNOR

Occasionally, psychiatric patients detained in institutions against their will or residing in the community under legal restraints elope and commit serious offenses. The authors looked at the frequency with which this occurred with patients on warrants of the Lieutenant-Governor in Ontario. Using the files of the Ontario Lieutenant-Governors Board of Review, they examined the records and isolated such recorded incidents over a 16 year period. In spite of the limitations identified by the authors, their findings indicate a lower than expected occurrence. As well, they point to the risk management implications of certain diagnostic groups being treated in a less than secure setting.

Persons discharged from warrants of the lieutenant governor

The authors compiled demographic, psychiatric, and criminological information on persons who were held on warrants of the Lieutenant Governor in Ontario. These warrants were vacated between the period 1969–1982. Of the entire population of 296 such persons, 46% were held as being Unfit to Stand Trial, 51% were Not Guilty by Reason of Insanity, and the remainder were Mentally Ill prisoners. Separate analyses were conducted with the Unfit sample. The average length of confinement on a warrant was 7 years.