DEGENERATIVE DISEASE AFFECTING THE NERVOUS SYSTEM1 1Delivered at the XIII Biennial Congress of the Australian Physiotherapy Association, Brisbane, August, 1973.

The term “degenerative disease” is one which is rather widely used in relation to the nervous system and yet one which is rarely formally and carefully defined. The term appears to be applied to disorders of the nervous system which often occur in later life and which are of uncertain cause. In the Shorter Oxford Dictionary the word degeneration is defined as “a change of structure by which an organism, or an organ, assumes the form of a lower type”. However this is not quite the sense in which the word is applied in human neuropathology, where it is conventional to restrict the use of the word to those organic disorders which are of uncertain or poorly understood cause and in which there is a deterioration or regression in the level of functioning of the nervous system. The concept of degenerative disorder is applied to other organs as well as to the brain, and as disease elsewhere in the body may affect the nervous system, it seems reasonable to include within the topic of degenerative disorder affecting the nervous system those conditions in which the nervous system is involved as a result of primary degenerations in other parts of the body

Effect of food on absorption of lomefloxacin

Twelve subjects participated in an open-label, single-dose, balanced three-way crossover study in which the absorptions of lomefloxacin were compared following (i) an overnight fast, (ii) a carbohydrate meal, and (iii) a high-fat meal. The time to peak concentration of lomefloxacin was delayed, but peak concentration in plasma and amount of drug absorbed were unchanged following both meals

Rascall: Rapid (Ra) screening (Sc) of RNA-seq data for prognostically significant genomic alterations in acute lymphoblastic leukaemia (ALL)

RNA-sequencing (RNA-seq) efforts in acute lymphoblastic leukaemia (ALL) have identified numerous prognostically significant genomic alterations which can guide diagnostic risk stratification and treatment choices when detected early. However, integrating RNA-seq in a clinical setting requires rapid detection and accurate reporting of clinically relevant alterations. Here we present RaScALL, an implementation of the k-mer based variant detection tool km, capable of identifying more than 100 prognostically significant lesions observed in ALL, including gene fusions, single nucleotide variants and focal gene deletions. We compared genomic alterations detected by RaScALL and those reported by alignment-based de novo variant detection tools in a study cohort of 180 Australian patient samples. Results were validated using 100 patient samples from a published North American cohort. RaScALL demonstrated a high degree of accuracy for reporting subtype defining genomic alterations. Gene fusions, including difficult to detect fusions involving EPOR and DUX4, were accurately identified in 98% of reported cases in the study cohort (n = 164) and 95% of samples (n = 63) in the validation cohort. Pathogenic sequence variants were correctly identified in 75% of tested samples, including all cases involving subtype defining variants PAX5 p.P80R (n = 12) and IKZF1 p.N159Y (n = 4). Intragenic IKZF1 deletions resulting in aberrant transcript isoforms were also detectable with 98% accuracy. Importantly, the median analysis time for detection of all targeted alterations averaged 22 minutes per sample, significantly shorter than standard alignment-based approaches. The application of RaScALL enables rapid identification and reporting of previously identified genomic alterations of known clinical relevance.Jacqueline Rehn, Chelsea Mayoh, Susan L Heatley, Barbara J McClure, Laura N Eadie, Caitlin Schutz, David T Yeung, Mark J Cowley, James Breen, Deborah L Whit

Sir Charles Locock and potassium bromide

On 12 May 1857, Edward Sieveking read a paper on epilepsy to the Royal Medical and Chirurgical Society in London. During the discussion that followed Sir Charles Locock, obstetrician to Queen Victoria, was reported to have commented that during the past 14 months he had used potassium bromide to successfully stop epileptic seizures in all but one of 14 or 15 women with 'hysterical' or catamenial epilepsy. This report of Locock's comment has generally given him credit for introducing the first reasonably effective antiepileptic drug into medical practice. However examination of the original reports raises questions as to how soundly based the accounts of Locock's comments were. Subsequently, others using the drug to treat epilepsy failed to obtain the degree of benefit that the reports of Locock's comments would have led them to expect. The drug might not have come into more widespread use as a result, had not Samuel Wilks provided good, independent evidence for the drug's antiepileptic efficacy in 1861

Problems in the Assessment of Potential Antiepileptic Drugs

Epilepsy is a serious and common neurological disorder for which effective and well tolerated new agents continue to be sought. While the assessment of potential antiepileptic agents in animals models of epilepsy poses few problems, such assessment in humans is fraught with methodological and ethical dilemmas. Before the introduction of controlled clinical trials, agents that were though to have antiepileptic potential were merely administered to patients with epilepsy and the effects observed. Nowadays, many controls are placed on the testing of all new pharmacological agents, including antiepileptic drugs. The simplest method of assessing the efficacy of a new antiepileptic agent in humans is in a monotherapy, placebo-controlled trial. However, such a trial design poses serious ethical and moral issues due to the importance of achieving early optimal control of epileptic seizures in patients. Because of these difficulties, placebo-controlled monotherapy trials are rarely performed. Instead, add-on and crossover designs are used, each of which has its own inherent disadvantages. Thus, the ideal trial design which allows accurate and simple assessment of the efficacy of a new antiepileptic agent has still to be developed

The I.L.A.E. classification of the epilepsies applied retrospectively to 1902 patients

The I.L.A.E. classification of the epilepsies and epileptic syndromes was applied retrospectively to the epileptic seizure disorders of 1902 consecutive patients collected from a neurological consultant practice over a 30 year period. There were 265 patients with only a solitary seizure when they presented. These 265 included fewer instances of generalized epilepsies (14.0% versus 28.5%) and more instances of epilepsies of undetermined type (35.1% versus 20.4%) than the remaining 1637 patients. It was possible to categorize the epilepsy or epileptic syndrome present in 77.6% of all cases. The remainder could not be classified on the evidence available and thus fell into the I.L.A.E. classification's category of 'epilepsies and syndromes undetermined whether focal or generalized'. The number of cases of such epilepsy of undetermined type decreased with increasing number of occasions on which patients were seen. Allowing for the effects of factors such as different age distributions in the various published series (in most series generalized epilepsies were more common in children), the distribution of epilepsies and epileptic syndromes diagnosed retrospectively in the present series was quite consonant with the data reported in the literature from contemporaneous series. In the various published series there were notable differences in the proportions of subjects allocated to the category of 'epilepsies and syndromes undetermined whether focal or generalized'. This raises the possibility that the categorizers' degrees of diagnostic confidence may have had appreciable effects on the reported distributions of epileptic syndromes in the different series. Some consensus regarding the degree of diagnostic probability acceptable for assigning a patient to a particular epileptic syndrome might yield more uniform outcomes from future epilepsy classificational attempts

The explosive Copula of Thomas Willis.

Thomas Willis (1621-1675), arguably the founding father of neurology, devised an interpretation of neurophysiology which involved motor function being mediated by explosions in nerve tissue and muscle, facilitated by the temporary development of an explosive Copula comprising short-lived aggregates of 'nitrous' and 'sulphur' particles i.e. the components of gunpowder. Seen from a modern standpoint, such a concept is manifestly absurd. However, seen from the standpoint of the Paracelsian iatrochemistry to which Willis subscribed, and understood in the spirit of analogy which he probably intended, Willis' interpretation can be regarded as the beginning of the application of bioenergetics to neural function