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Biomedical subjects

Ian McDonald

Publications and source records attributed to Ian McDonald.

10 recordsLinked to original sources
PubMed2007

Gordon Holmes Lecture: Gordon Holmes and the neurological heritage.

Sir Gordon Holmes is one of the great figures in the history of twentienth century neurology. In him, there came together the traditions of German and British neurology which moulded a physiological approach to normal and disordered function of the nervous system with a commitment to interpreting clinical phenomena in the light of meticulous pathological examination. He, more than any other individual, was responsible for the form of the neurological examination as it is now performed; and his insights are fundamental to the way that, nowadays, we think about vision, somato-sensory function, the spinal cord and the cerebellum.

Cerebellum↗
PubMed2006

Musical alexia with recovery: a personal account.

I describe the experience of an acute loss of ability to read music and play the piano accurately and expressively following an embolic infarct of the right angular and supramarginal gyri in a setting of chronic migraine. Other parietal deficits included a small visual field defect, visual hallucinations, prosopagnosia, topographical disorientation, disturbance of perception of velocity of moving objects and dyscalculia. Recovery began within a month of the ictus after instituting a regular practice routine. The ability to read and play polyphony recovered before the ability to read homophonic music. A substantial degree of recovery of musical function occurred within 6 months and of the other parietal deficits over a year. Failure to maintain regular practice led to marked though recoverable deterioration. An increased frequency of migraine persisted for some 18 months.

Aged↗
PubMed2005

Reductions in beta-amyloid concentrations in vivo by the gamma-secretase inhibitors BMS-289948 and BMS-299897.

A primary pathological feature of Alzheimer's disease is beta-amyloid (Abeta)-containing plaques in brain and cerebral vasculature. Reductions in the formation of Abeta peptides by gamma-secretase inhibitors may be a viable therapy for reducing Abeta in Alzheimer's disease. Here we report on the effects of two orally active gamma-secretase inhibitors. BMS-289948 (4-chloro-N-(2,5-difluorophenyl)-N-((1R)-{4-fluoro-2-[3-(1H-imidazol-1-yl)propyl]phenyl}ethyl)benzenesulfonamide hydrochloride) and BMS-299897 (4-[2-((1R)-1-{[(4-chlorophenyl)sulfonyl]-2,5-difluoroanilino}ethyl)-5-fluorophenyl]butanoic acid) markedly reduced both brain and plasma Abeta(1-40) in APP-YAC mice with ED(50) values of 86 and 22 mg/kg per os (po), respectively, for BMS-289948, and 30 and 16 mg/kg po, respectively, for BMS-299897. Both compounds also dose-dependently increased brain concentrations of APP carboxy-terminal fragments, consistent with inhibition of gamma-secretase. BMS-289948 and BMS-299897 (100 mg/kg po) reduced brain and plasma Abeta(1-40) rapidly (within 20min) and maximally within 3 h. BMS-299897 also dose-dependently reduced cortical, cerebrospinal fluid (CSF), and plasma Abeta in guinea pigs with ED(50) values of 30 mg/kg intraperitoneally, without affecting CSF levels of alpha-sAPP. The reductions in cortical Abeta correlated significantly with the reductions in both plasma (r(2) = 0.77) and CSF (r(2) = 0.61) Abeta. The decreases in Abeta were apparent at 3 and 6 h post-administration of BMS-299897, but not at 12h. These results demonstrate that BMS-289948 and BMS-299897 are orally bioavailable, functional gamma-secretase inhibitors with the ability to markedly reduce Abeta peptide concentrations in APP-YAC transgenic mice and in guinea pigs. These compounds may be useful pharmacologically for examining the effects of reductions in beta-amyloid peptides in both animal models and in Alzheimer's disease.

Alzheimer Disease↗
PubMed2005

Degradation of organic pollutants by methane grown microbial consortia.

Microbial consortia were enriched from various environmental samples with methane as the sole carbon and energy source. Selected consortia that showed a capacity for co-oxidation of naphthalene were screened for their ability to degrade methyl-tert-butyl-ether (MTBE), phthalic acid esters (PAE), benzene, xylene and toluene (BTX). MTBE was not removed within 24 h by any of the consortia examined. One consortium enriched from activated sludge ("AAE-A2"), degraded PAE, including (butyl-benzyl)phthalate (BBP), and di-(butyl)phthalate (DBP). PAE have not previously been described as substrates for methanotrophic consortia. The apparent Km and Vmax for DBP degradation by AAE-A2 at 20 degrees C was 3.1 +/- 1.2 mg l(-1) and 8.7 +/- 1.1 mg DBP (g protein x h)(-1), respectively. AAE-A2 also showed fast degradation of BTX (230 +/- 30 nmol benzene (mg protein x h)(-1) at 20 degrees C). Additionally, AAE-A2 degraded benzene continuously for 2 weeks. In contrast, a pure culture of the methanotroph Methylosinus trichosporium OB3b ceased benzene degradation after only 2 days. Experiments with methane mono-oxygenase inhibitors or competitive substrates suggested that BTX degradation was carried out by methane-oxidizing bacteria in the consortium, whereas the degradation of PAE was carried out by non-methanotrophic bacteria co-existing with methanotrophs. The composition of the consortium (AAE-A2) based on polar lipid fatty acid (PLFA) profiles showed dominance of type II methanotrophs (83-92% of biomass). Phylogeny based on a 16S-rRNA gene clone library revealed that the dominating methanotrophs belonged to Methylosinus/Methylocystis spp. and that members of at least 4 different non-methanotrophic genera were present (Pseudomonas, Flavobacterium, Janthinobacterium and Rubivivax).

Bacteria↗
PubMed2004

Multiple sclerosis in its European matrix: some aspects of history, mechanisms and treatment.

Susceptibility to multiple sclerosis is influenced by several genes which are relatively common in populations of European origin. Their precise identification is currently being intensively investigated. The pathophysiology of the main clinical features is better understood. Relapse results from abnormalities of conduction to which both demyelination and inflammation contribute. At the membrane level, remission depends on the formation of new sodium channels which restore conduction even in persistently demyelinated axons. Remyelination presumably contributes and synaptic reorganisation may also do so. Axonal degeneration contributes to irrecoverable deficit and progression of disability. These observations suggest new therapeutic strategies. The management of multiple sclerosis needs to be improved. Progress requires an ethically based partnership between patients, whose needs are paramount, the research and caring communities and the pharmaceutical industry.

Europe↗
PubMed2003

3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-pyridine: a potent and highly selective metabotropic glutamate subtype 5 receptor antagonist with anxiolytic activity.

2-Methyl-6-(phenylethynyl)pyridine (3), a potent noncompetitive mGlu5 receptor antagonist widely used to characterize the pharmacology of mGlu5 receptors, suffers from a number of shortcomings as a therapeutic agent, including off-target activity and poor aqueous solubility. Seeking to improve the properties of 3 led to the synthesis of compound 9, a highly selective mGlu5 receptor antagonist that is 5-fold more potent than 3 in the rat fear-potentiated startle model of anxiety.

Anti-Anxiety Agents↗
PubMed2002

International concerted action on collaboration in telemedicine: recommendations of the G-8 Global Healthcare Applications Subproject-4.

The main objectives of the G-8 Global Healthcare Applications Subproject-4 (G-8 GHAP-SP-4) were to establish an international concerted action on collaboration in telemedicine, telehealth, and health telematics (hereafter referred in this paper as telemedicine). In order to promote and facilitate the implementation of telemedicine or health telematics networks around the world, it was considered necessary to address certain key issues. Five thematic solution-seeking forums were held between May 1998 and December 1999. Each addressed a key issue, including interoperability of telemedicine and telehealth systems, impact of telemedicine on health care management, evaluation and cost effectiveness of telemedicine, clinical and technical quality and standards, and medico-legal aspects of national and international applications. The main objectives of these forums were to establish best practices and a thorough review of the issues and discussions among experts to determine the best solutions for the facilitation of global international telemedicine networks. More than 650 invited participants from 16 countries attended the five forums, which were of 2-3 days in duration. These forums provided a foundation for the exchange of ideas resulting in the initiation of collaborative activities. Based on these deliberations, a series of 21 recommendations were prepared by the national representatives of the G-8 GHAP SP-4. These recommendations propose to political leaders and health care managers of the G-8 and other countries roadmaps to follow in order to accelerate the achievement of a Global Society of Healthcare via Telemedicine, Telehealth, and Health Telematics. The 21 recommendations are presented in this report.

Humans↗
PubMedDate not supplied

Deficit, recovery and the vis nervosa.

Physicians have long sought to explain neurological deficit and recovery on the basis of alterations in the agent of nervous action. The ancient Greeks knew that the brain influences muscles and they showed experimentally that the effects were mediated by nerves. Galen believed that the agent of action was the animal spirits. Ideas began to change with a new approach to knowledge and the revival of experimentation that followed the arrival in Venice of ancient Greek manuscripts after the fall of Constantinople in 1453. In the mid-18th century the notion of animal spirits was replaced by that of the vis nervosa and speculation began that the agent might be electrical. This was established by the mid-19th century. The nature of conduction in nerve was clearly different from that in a wire but how it took place remained uncertain until Hodgkin and Huxley proved the ionic hypothesis in the mid-20th century. In the following decades the membrane mechanisms of conduction failure and restoration were elucidated, with practical consequences in the form of improved diagnostic methods and the potential for more rational approaches to treatment. The demonstration that adaptive cortical plasticity contributes to recovery raises the possibility of new strategies for neurological rehabilitation.

Brain↗