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S Hume

Publications and source records attributed to S Hume.

11 recordsLinked to original sources
PubMed2001

Effect of 5-HT on binding of [(11)C] WAY 100635 to 5-HT(IA) receptors in rat brain, assessed using in vivo microdialysis nd PET after fenfluramine.

By using a combination of positron emission tomography (PET) and postmortem tissue dissection, the effect of increased endogenous serotonin on specific binding of [(11)C]WAY 100635 to the 5-HT(1A) receptor was investigated in rat brain in vivo. The binding studies were complemented by in vivo microdialysis to monitor 5-HT levels in similarly treated isoflurane-anaesthetised rats, with the dialysis probe locations corresponding to two of the tissues sampled for specific binding of the radioligand. Fenfluramine treatment (10 mg/kg i.p.) resulted in a approximately 5-fold increase in extracellular 5-HT in medial prefrontal cortex and a approximately 15-fold increase in lateral hippocampus, maximal at approximately 40 min after injection. PET scan duration was either 60 or 90 min, beginning 30 min after fenfluramine injection. The specific binding of [(11)C]WAY 100635 was reduced by 10-20% in hippocampus, which showed highest binding in control animals. Specific binding, however, was unaffected in both prefrontal cortex and midbrain raphe, each additional high binding regions. The minimal effects are consistent with a low baseline occupancy of the 5-HT(1A) receptor by 5-HT in vivo, so that only a large change in endogenous agonist concentration will affect radioligand binding. This implies that utilisation of [(11)C]WAY 100635 in human PET to quantify 5-HT(1A) receptor expression can be extended to pathology where synaptic 5-HT levels are altered as a consequence of the disease state.

Animals↗
PubMed2000

Pindolol occupancy of 5-HT(1A) receptors measured in vivo using small animal positron emission tomography with carbon-11 labeled WAY 100635.

Positron emission tomography (PET), following an intravenous injection of [carbonyl-(11)C]WAY 100635, was used to image central 5-HT(1A) receptors in rat following pretreatment with graded doses of (-)-pindolol (0.001-3 mg/kg, i.v.). The use of PET had advantages over ex vivo radioligand binding methods in that it produced parametric image volumes and reduced errors due to inter-rat variability. Time-radioactivity curves from regions of interest (ROI) acquired from individual rats enabled the estimation of specific binding of the radioligand using a compartmental model with reference tissue input. Binding potential (BP) of [(11)C]WAY 100635 was estimated for frontal cortex and hippocampus (postsynaptic), and midbrain raphe nuclei (presynaptic). In the latter ROI, pindolol dose-dependently decreased BP. The saturation curve could be fitted to a single-site model up to the lowest dose of pindolol used, giving an ED(50) (dose to cause 50% occupancy) value of 0.26 +/- 0. 05 mg/kg, and inclusion of control (nonpindolol-treated) rats did not affect the fit. In contrast, in cortex and hippocampus ROI, low doses of pindolol caused an increase in BP compared with controls. Pindolol doses greater than approximately 0.1 mg/kg, resulted in a dose-dependent decrease in BP, and ED(50) values in cortex and hippocampus were estimated as 0.44 +/- 0.13 and 0.48 +/- 0.12 mg/kg, respectively. The increase in [(11)C]WAY 100635 binding at low pindolol doses is feasibly related to a decrease in basal receptor occupancy following reduced release of endogenous 5-HT. Considering the apparently greater potency of pindolol at the midbrain raphe ROI, this effect could be mediated via agonist activity at the autoreceptor.

Animals↗
PubMed1999

Radio-imaging in small animals.

As the resolution of radio-imaging systems improves, the prospect of in-vivo imaging of small animals becomes more attractive. Purpose-built positron emission tomography (PET) scanners capable of imaging individual tissues within the rat brain are now in routine experimental use and in-vivo tracer and saturation-kinetic studies are now possible. The study of small animals in this way does have intrinsic problems and constraints associated with it. For example, the animal must be completely immobilized, stable ligand within the radiolabelled preparation may be limiting and anatomical definition may be poor. In spite of this, consistent, semi-quantitative data can be produced and in-vivo radio-imaging can provide a genuine and unique complement to more conventional techniques. Animal numbers can be significantly reduced and the quality of data improved due to reduced inter-animal variation, and longitudinal studies, to monitor disease progression, are feasible. As the resolution of imaging systems improves still further, such studies could be extended to mouse, in addition to rat, models of disease.

Animals↗
PubMed1991

A cost-minimization study of cancer patients requiring a narcotic infusion in hospital and at home.

We conducted a retrospective, non-randomized, cost-minimization study, from the perspective of the Ministry of Health, to compare the cost of managing cancer patients who required narcotic infusions, in hospital and at home. Our medical costs averaged $369.72 per inpatient day and $150.24 per outpatient day (saving $219.48 per diem, 1988 Canadian dollars), while narcotic costs were the same for any given patient in both settings. Sensitivity analysis showed that no reasonable changes in the quantity and cost of services reduced our savings by more than 50%. During incremental analysis, savings increased as more outpatient days were managed by our centre, from $0.00 for 318 days, to more than $500,000 for over 2000 days per annum. As this program has been extremely cost effective and preferred by our patients, other hospitals and central funding agencies might consider establishing a regional outpatient narcotic infusion program to reduce their costs.

Canada↗
PubMed1990

Inpatient narcotic infusions for patients with cancer pain.

Morphine and hydromorphone infusions of 6 or more (average 25.75) days in duration were used with increasing frequency (up to 7%) by our oncology inpatients. Eighty-six percent of the 135 inpatients we reviewed realized good pain control with dose rates up to 700 morphine-equivalent (ME) mg/h. Local toxicity occurred on only 10 occasions. Systemic side effects secondary to the infusion were reported 75 times and were generally readily reversed. Myoclonus was seen in 11% of our patients at dose rates as low as 60-90 ME mg/h. Adjuvant therapies were not used as frequently as might be warranted. We believe that narcotic infusions, particularly subcutaneous ones, are safe and effective. Further prospective trials are needed to clarify how they should be combined with other therapies to control cancer pain that is poorly responsive to narcotics, and to better understand the etiology and management of serious side effects.

Adult↗
PubMedDate not supplied

Choosing the right inhaler for patients with asthma.

This article assesses the suitability of inhaler devices for patients with asthma according to their individual needs. Three main types of inhalers are discussed: pressurised metered dose inhalers, breath-actuated inhalers and dry powder inhalers. The advantages and disadvantages of these devices are discussed in relation to lifestyle, ability and suitability for individuals.

Activities of Daily Living↗
PubMedDate not supplied

A longitudinal study of the change in resistance patterns and genetic relationship of oral Candida albicans from HIV-infected patients.

Candida albicans is an important opportunistic pathogen in the oral cavity of HIV-infected patients. C. albicans was isolated repeatedly over a period of 30 months from the mouth-swills of five males with category IV HIV infection who suffered from recurrent pseudomembranous oral candidosis and were being treated with fluconazole. C. albicans was identified by the germ tube test, carbon assimilation by the API 20C test (bioMerieux sa, Marcy, l'Etoile, France) and morphology on cornmeal Tween 20 agar. Sensitivity testing was performed with a disk diffusion method using neosensitabs (Rosco Diagnostica, Taasrup, Denmark) and the broth microdilution assay using RPMI 1640 medium. Isolates from the five patients taken between 14 and 30 months apart (mean = 23 months) showed the development of resistance to several antifungal agents, notably fluconazole, miconazole and itraconazole by the disc diffusion method and markedly higher minimum inhibitory concentrations (MICs) for fluconazole by the broth microdilution assay. Genetic relatedness of the C. albicans strains was assessed using the mixed-linker polymerase chain reaction method. Four patients had isolates which were genetically identical, while one patient had isolates of varying genetic type. This study has shown that in HIV-infected patients with recurrent oral pseudomembraneous candidosis, the development of drug resistance to antifungal agents may either be due to increased resistance of a single strain or replacement with a more resistant strain.

AIDS-Related Opportunistic Infections↗