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Biomedical subjects

S McLean

Publications and source records attributed to S McLean.

At least 19 recordsLinked to original sources
PubMed2005

The role of physiotherapy in the management of non-specific back pain and neck pain.

This paper provides an overview of best practice for the role of physiotherapy in managing back pain and neck pain, based mainly on evidence-based guidelines and systematic reviews. More up-to-date relevant primary research is also highlighted. A stepped approach is recommended in which the physiotherapist initially takes a history and carries out a physical examination to exclude any potentially serious pathology and identify any particular functional deficits. Initially, advice providing simple messages of explanation and reassurance will form the basis of a patient education package. Self-management is emphasized throughout. A return to normal activities is encouraged. For the patient who is not recovering after a few weeks, a short course of physiotherapy may be offered. This should be based on an active management approach, such as exercise therapy. Manual therapy should also be considered. Any passive treatment should only be used if required to relieve pain and assist in helping patients get moving. Barriers to recovery need to be explored. Those few patients who have persistent pain and disability that interferes with their daily lives and work need more intensive treatment or a different approach. A multidisciplinary approach may then be optimal, although it is not widely available. Liaison with the workplace and/or social services may be important. Getting all players on side is crucial, especially at this stage.

Back Pain↗
PubMed2005

Constituents of Agave americana and Agave barbadensis.

An investigation of Agave americana and Agave barbadensis resulted in the isolation of a new homoisoflavanoid, 7-hydroxy-3-(4-methoxybenzyl)-chroman (3), together with known compounds 7-hydroxy-3-(4-methoxybenzyl)-chroman-4-one (1), 5,7-dihydroxy-3-(4-methoxybenzyl)-chroman-4-one (2), cantalasaponin-1 (4), and 2-hydroxy-butanedioic acid-1-methyl ester (5).

Agave↗
PubMed2005

Quantifying the passive extensibility of the flexor pollicis longus muscle in people with tetraplegia.

STUDY DESIGN: Repeat measures design. OBJECTIVE: The purpose of this study was firstly, to describe a simple clinical tool that can be used to measure the extensibility of the flexor pollicis longus (FPL) muscle; secondly, to test its reliability; and thirdly, to attain some 'normative' data of the extensibility of the FPL muscle in a representative sample of people with tetraplegia. SETTING: A spinal cord injury unit in Sydney. SUBJECTS: A total of 37 people (62 hands) with C4-C7 tetraplegia. MAIN OUTCOME MEASURES: Angle of the carpometacarpal (CMC) joint of the thumb was measured in all subjects with the application of a series of thumb extensor torques. A device specifically designed for this purpose was used to standardize the torque and objectively quantify the CMC joint angle. In addition, repeat measurements were taken 3-5 days later in one subgroup of 13 subjects (one hand per subject) and 3 months later in another subgroup of 13 subjects (one hand per subject). ANALYSIS: Intraclass correlation coefficients and percent close agreement scores were derived to quantify the 3-5 days and 3-month reliability between repeat measurements. RESULTS: The median CMC angle of the thumb with the application of a 0.044 Nm torque was 63 degrees (range, 20-93 degrees). The intraclass correlation coefficients with the application of a 0.044 Nm torque were 0.88 (95% CI, 0.65-0.96) for measurements taken 3-5 days apart, and 0.90 (95% CI, 0.67-0.97) for measurements taken 3 months apart. CONCLUSION: This study describes a simple and reliable way of measuring the extensibility of the FPL muscle in people with tetraplegia. This assessment tool and the 'normative' data provided in this study can be used to further investigate the contribution of the passive mechanical properties of the FPL muscle to hand function of people with C6 and C7 tetraplegia.

Adult↗
PubMed2005

Do substance P and the NK1 receptor have a role in depression and anxiety?

Research on Substance P (SP) has, until recently, focused on its role in pain and inflammation. However, a report that NK(1) receptor antagonists have utility in the treatment of depression has stimulated research into the function of SP and the NK(1)receptor in anxiety and depression. The distribution of SP and the NK(1) receptor in brain areas implicated in anxiety and depression is initially reviewed. This is followed by evaluation of the preclinical data obtained for SP and NK(1) receptor antagonists in behavioral models of depression as well as the phenotype of genetically modified animals lacking the genes encoding for the NK(1) receptor or for SP. The weight of the evidence supports antidepressant and anxiolytic activity of NK(1) receptor antagonists. However, many of the studies do not control for nonspecific effects of the compounds, and when enantiomers that lack activity at the NK(1) receptor are included, the results, in some cases, suggest that blockade of NK(1) receptors does not account for the observed behavioral activity. Finally, clinical studies in depressed patients assessing SP levels in plasma and cerebrospinal fluid as well as the effect of NK(1) receptor antagonists are reviewed. The clinical studies are a mixture of positive, failed and negative studies on the antidepressant activity of NK(1) receptor antagonists, not unlike the early clinical results obtained with selective serotonin reuptake inhibitors.

Amygdala↗
PubMed2003

Biological monitoring of low level occupational xylene exposure and the role of recent exposure.

The correlation between low level time-weighted average (TWA) atmospheric xylene exposure (p.p.m.) and urinary methylhippuric acid (MHA) expressed per gram of creatinine was examined. Subjects were recruited from workplaces that utilized xylene. Ambient monitoring of o-, m- and p-xylene isomers was carried out using passive diffusion vapour monitors. Adjusted (post-shift minus pre-shift) and post-shift urinary levels of xylene metabolites (2-, 3- and 4-MHA) were determined by GC-MS. Twenty subjects were recruited into the study. Total xylene TWA exposures were 3.36 +/- 3.63 p.p.m. (mean +/- SD) with a range of 0.03-14.44 p.p.m. The r(2) values for the regression equations between xylene exposure and individual and total adjusted MHA isomers were 0.390, 0.709, 0.677 and 0.631 for o-, m-, p- and total xylenes, respectively, which was greater than the respective correlations between non-adjusted samples. In conclusion, biological monitoring of occupational xylene exposure at levels <15 p.p.m. using urinary MHA showed a good correlation with atmospheric levels and is a valid complement to ambient monitoring. Even though occupational xylene exposure in the workplaces studied was generally low, MHA was found in the pre-shift urine of all workers and the use of adjusted values showed modest improvements in correlations. Recent exposure prior to sampling, either from occupational or non-occupational sources, should be considered when biological monitoring of xylene is undertaken. Extrapolation of data from this study predicted a MHA concentration in post-shift urine of 1.3 g/g creatinine after exposure to a TWA of 100 p.p.m. xylene.

Adult↗
PubMed2002

Inhibition of the microsomal metabolism of 1,8-cineole in the common brushtail possum (Trichosurus vulpecula) by terpenes and other chemicals.

1. Brushtail possums (Trichosurus vulpecula) ingest large amounts of terpenes in their diet of Eucalyptus leaf. Previously, we showed that dietary terpenes induce the cytochrome P450 enzymes (CYPs) responsible for their metabolism. The present study examined the effects of various CYP inhibitors on the metabolism of 1,8-cineole, the major dietary terpene, by liver microsomes from the possum and rat. 2. Ketoconazole inhibited the major reactions of terpene-induced microsomes in both species: 9-hydroxylation in the possum and 2-hydroxylation in the rat. This suggests the involvement of CYP3A enzymes, although in the possum there was a lack of the expected inhibition by troleandomycin or activation by alpha-naphthoflavone, highlighting the differences between species in CYP forms. Diethyldithiocarbamate also inhibited 9-hydroxylation in the possum, indicating that a CYP2E1-like enzyme contributes to this reaction. 3. Three other dietary terpenes were potent competitive inhibitors of 9-hydroxylation in the possum. K(i) ( micro M) (mean +/- SE, n = 4) were: alpha-pinene, 4.4 +/- 1.1; limonene, 7.8 +/- 2.1; p-cymene, 44.3 +/- 11.2; cuminyl alcohol (a p-cymene metabolite), 6.0 +/- 0.8. It appears likely that p-cymene acts via its metabolite to inhibit 1,8-cineole metabolism. 4. Inhibitory interactions between dietary terpenes, as well as other plant secondary compounds, may impose a significant constraint on foliage consumption in the common brushtail possum, therefore explaining the obligatory generalist nature of this browsing marsupial and other generalist herbivores.

Animals↗
PubMed2002

Microsomal metabolism and enzyme kinetics of the terpene p-cymene in the common brushtail possum (Trichosurus vulpecula), koala (Phascolarctos cinereus) and rat.

1. p-Cymene is an aromatic monoterpene found in the leaves of Eucalyptus spp. and is ingested in the diet of two marsupial folivores, the brushtail possum (Trichosurus vulpecula) and koala (Phascolarctos cinereus). The metabolism of p-cymene by liver microsomes from the possum, koala and rat (an animal whose diet is not terpene-rich) was examined. 2. The major p-cymene metabolite in each species was cuminyl alcohol, with smaller amounts of other side-chain alcohols being formed. No phenolic metabolites were detected. Possum and koala microsomes further oxidized cuminyl alcohol to cumic acid. 3. Pretreatment with a terpene diet more than doubled the V(max) for cuminyl alcohol formation by possum microsomes. This is similar to a previous finding by our group with 1,8-cineole and indicates that a terpene-containing diet results in induction of the enzymes responsible for terpene metabolism. 4. The rank order of the ability to metabolize p-cymene, measured by intrinsic clearance (Cl(int) = V(max)/K(m) [microl mg protein(-1) min(-1)]) was: terpene-treated possum (128)>control possum (107)>koala (69)>rat (38). 5. The findings support the hypothesis that animals that have adapted to a diet of Eucalypus leaf have a greater capacity than generalist feeders to metabolize dietary terpenes.

Adaptation, Physiological↗
PubMed2001

Metabolites of dietary 1,8-cineole in the male koala (Phascolarctos cinereus).

The in vivo metabolic fate of 1,8-cineole was investigated in six male koalas. Koalas were fed ad lib a diet of Eucalyptus cephalocarpa leaf with a 1,8-cineole concentration of 2.53+/-0.70% dry mass of leaf, corresponding to a 1,8-cineole intake of 2.4+/-1.1 mmol/kg (3.1+/-1.3 g). Urine and faeces were collected for 24 h and metabolites identified by GC-MS and LC-MS. Metabolites were quantified before and after hydrolysis with beta-glucuronidase to give free and total levels, respectively. Fractional recovery of ingested 1,8-cineole was 1.3+/-0.4 and 1.4+/-0.4 (mean+/-S.D.) for free and total measurements, respectively. Seven metabolites were identified and quantified: 9- and 7-hydroxycineole, 9- and 7-cineolic acid, 7-hydroxy-9-cineolic acid, 9-hydroxy-7-cineolic acid and 7,9-dicineolic acid. The hydroxycineolic acids dominated the metabolite profile (85%). 7,9-Dicineolic acid, a novel metabolite of 1,8-cineole, accounted for almost 10% of the recovered dose making it the second most abundant metabolite after 7-hydroxy-9-cineolic acid (77%). Together, the less oxidised metabolites, the hydroxycineoles and cineolic acid, accounted for only 5% of the cineole consumed. Significant conjugation only occurred with four minor, less oxidised, alcohol and carboxylic acid metabolites. We have shown that the koala detoxifies and eliminates 1,8-cineole primarily by extensive oxidation without utilising conjugation pathways.

Animals↗
PubMed2001

Prenylated benzophenone derivatives from Clusia havetiodes var. stenocarpa.

Extracts of the fruit of Clusia havetiodes var. stenocarpa have yielded three new prenylated benzophenone derivatives, 28,29-epoxyplukenetione A (1), 33-hydroperoxyisoplukenetione C (2), and 15,16-dihydro-16-hydroperoxyplukenetione F (3), as well as four which have been previously described, plukenetiones C, F, and G and sampsonione G.

Benzophenones↗
PubMed2001

New diterpenes from Jatropha divaricata.

Extracts of the stems of Jatropha divaricata have yielded the two new diterpenes ent-3 beta,14 alpha-hydroxypimara-7,9(11),15-triene-12-one (3) and the rearranged pimarane ent-15(13-->8)abeo-8 beta(ethyl)pimarane (4), which appears to be a new skeletal type. The rare cleistanthane diterpenes spruceanol (1) and cleistanthol (2) were also obtained.

Diterpenes↗
PubMed2001

Does excretion of secondary metabolites always involve a measurable metabolic cost? Fate of plant antifeedant salicin in common brushtail possum, Trichosurus vulpecula.

Salicin was administered orally to six brushtail possums by incorporation in food for six days at three dose levels (0.05, 0.5, and 1.5% wet weight), giving mean +/- SD daily intakes of 0.31 +/- 0.09, 2.76 +/- 0.75, and 6.04 +/- 1.12 mmol salicin. Metabolites were identified by mass spectrometry and assayed by HPLC. Salicyl alcohol glucuronide accounted for 56-64% of urinary metabolites over the three doses, salicyluric acid 15-26%, salicin 10-18%, and there were smaller amounts of free (2-4%) and conjugated (0-6%) salicylic acid. beta,2-Dihydroxyphenylpropionic acid was a minor metabolite. The hydrolysis of dietary salicin enabled reconjugation of its aglycone, salicyl alcohol, with a more polar sugar, glucuronic acid, thus enhancing its renal excretion and resulting in little net loss of substrates for conjugation and a low measurable metabolic cost of excretion.

Administration, Oral↗
PubMed2001

Expression of individual lamins in basal cell carcinomas of the skin.

In this study we used a unique collection of type specific anti-lamin antibodies to study lamin expression patterns in normal human skin and in skin derived from patients with basal cell carcinomas (BCCs). Lamin expression in serial sections from frozen tissue samples was investigated by single and double indirect immunofluorescence. In normal skin, lamin A was expressed in dermal fibroblasts and in suprabasal epithelial cells but was absent from all basal epithelial cells. Lamin C was expressed in dermal fibroblasts, suprabasal epithelial cells and a majority of basal epithelial cells. However, lamin C was not expressed in quiescent basal epithelial cells. Lamin B1 was expressed in all epithelial cells but was not expressed in dermal fibroblasts. Finally, lamin B2 was expressed in all epithelial cells but was not expressed in dermal fibroblasts. Finally, lamin B2 was expressed in all cell types in normal skin. Lamin expression was also investigated in a collection of 16 BCCs taken from a variety of body sites. Based upon patterns of lamin expression the BCCs were classified into four groups: A-negative (10/16 tumours), C-negative (5/16 tumours), A/C-negative (1/16 tumours) and A/B2-negative (1/16 tumours). Lamin expression was also compared to cell proliferation index by staining serial sections with the proliferation marker Ki67. 9/10 of the lamin A negative tumours were highly proliferative, whereas 4/5 of the lamin C negative tumours were slow growing. Thus as a general rule absence of lamin A was correlated with rapid growth within the tumour, while absence of lamin C was correlated with slow growth within the tumour. Our data supports the hypothesis that lamin A has a negative influence on cell proliferation and its down regulation may be a requisite of tumour progression.

Antibodies↗
PubMed2001

Microsomal metabolism of the terpene 1,8-cineole in the common brushtail possum (Trichosurus vulpecula), koala (Phascolarctos cinereus), rat and human.

1. This study reports on the pathways of metabolism and enzyme kinetics of the Eucalyptus terpene, 1,8-cineole, by liver microsomes from the brushtail possum (Trichosurus vulpecula) and koala (Phascolarctos cinereus) (animals that normally include this terpene in their diet), rat and human. 2. The rank order of the ability to metabolize 1,8-cineole with respect to overall 1,8-cineole intrinsic clearance (CL'int = Vmax/Kmax in microl mg protein(-1) min(-1)) was koala (188) > possum (181)>> rat (28) > human (12). This order supports the hypothesis that adaptation to a Eucalyptus diet involves enhanced metabolism of terpenes. 3. The metabolism of 1,8-cineole was also studied in the liver from brushtail possum pretreated with a mixture of terpenes, which have previously been shown to induce cytochrome P450 enzymes. Rats were pretreated with the same mixture of terpenes or phenobarbitone. 4. Terpene pretreatment more than doubled the CL'int of 1,8-cineole by brushtail possum liver microsomes (from 180 to 394 microl mg protein(-1) min(-1)) and increased rat CL'int by nearly 10-fold (from 28 to 259 microl mg protein(-1) min(-1)), but still less than the induced possum value. However, phenobarbitone had the greatest inducing effect, increasing the rat CL'int to 1,825 microl mg protein(-1) min(-1). 5. A regioselective preference of oxidation was evident between adapted and non-adapted species. In rat and human oxidation was preferred at the aliphatic ring carbons over methyl substituents. In possum, many of the available carbons were utilized, however metabolism at methyl substituents was preferred. In the koala, oxidation occurred primarily at the methyl substituents.

Adult↗
PubMed2001

P-glycoprotein efflux at the blood-brain barrier mediates differences in brain disposition and pharmacodynamics between two structurally related neurokinin-1 receptor antagonists.

CP-122721 and CP-141938 are potent and selective neurokinin-1 (NK(1)) receptor antagonists with very different brain disposition and potency in models of centrally mediated activity. These investigations sought to determine whether differences in potency were related to differences in P-glycoprotein (P-gp) transport at the blood-brain barrier. Both compounds stimulated ATPase activity of human recombinant MDR1 with similar kinetic parameters. Cell-associated drug concentrations of CP-141938 were 9.4-fold lower in KBV1 cells expressing P-gp compared with KB3.1 control cells. In Madin-Darby canine kidney (MDCK) cells expressing human MDR1, asymmetric transport of CP-141938 was 5-fold higher than in wild-type MDCK cells, whereas no asymmetry was observed with CP-122721. In agreement with these differences in cellular transport, the differences in brain/plasma ratio between mdr1a/b(-/-) and FVB mice 1 h following a 3 mg/kg s.c. dose were 3- and 50-fold for CP-122721 and CP-141938, respectively. The effect of inhibiting P-gp efflux on the effects of these agents was evaluated using GR73632-induced foot tapping in gerbils as a model to measure centrally mediated NK(1) antagonism. When gerbils were pretreated with the P-gp inhibitor MS-073 (50 mg/kg s.c.), there was no effect on the activity of CP-122721 (0.05 mg/kg), whereas the percent reversal for CP-141938 (10 mg/kg) increased from 60 to 100%. In gerbils, the brain/plasma ratio for CP-122721 was unaffected by MS-073 pretreatment, whereas the brain/plasma ratio for CP-141938 brain concentrations increased 13-fold. This suggested that P-gp efflux influences the brain disposition and pharmacologic activity of CP-141938, but not CP-122721. Complete response curves for CP-141938 were then determined with respect to dose, and drug concentration in the plasma and brain in the presence and absence of MS-073 pretreatment. The dose and plasma concentration-response curves of CP-141938 were shifted to the left in the presence of MS-073, yet brain concentrations associated with the response were unchanged. This suggested that once in the brain the interaction of CP-141938 with the NK(1) receptor was not affected by P-gp transport. In conclusion, these studies show that brain disposition and centrally mediated in vivo activity of NK(1) antagonists can be profoundly affected by P-gp transport and that such transport should be considered during the design of new agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

The Saskatchewan dissemination story.

The Saskatchewan Heart Health Program (SHHP) Dissemination Phase "Building Health Promotion Capacity" is a five-year program funded by Health Canada, Saskatchewan Health and the Heart and Stroke Foundation of Saskatchewan. This phase began in July 1998 and builds on two previous SHHP phases: the provincial heart health survey (Saskatchewan Health, 1990), and the community demonstration projects (SHHP, 1998a, b, c, d). The evolution of the SHHP has occurred in a dynamic provincial context. Saskatchewan is a Canadian prairie province of one million people with most living in the southern and central parts of the province. The population is ageing and urbanizing, and the economy is shifting away from agricultural production toward a diversified service sector. In 1993, health reform created 30 Districts in southern and central Saskatchewan; the formation of three northern Districts followed five years later. All but two Districts are rural-based. Population served ranges from 2,261 to 237,274; total area ranges from 4,019 to 133,900 square kilometers.

Cardiovascular Diseases↗
PubMed2000

Field immobilisation of southern elephant seals with intravenous tiletamine and zolazepam.

Southern elephant seals (Miroungo leonina) were immobilised with a mixture of tiletamine and zolazepam administered intravenously at a mean (sd) dose rate of 0.46 (0.08) mg/kg. This dose provided a satisfactory degree of anaesthesia with no side effects, and the induction, duration and recovery times were short. The mean (sd) induction time was 26 (9) seconds and the mean level of anaesthesia was 4.4 units on an eight-point scale. Male seals were given less drug than female seals, remained immobilised for shorter periods and recovered sooner. The mean (sd) dose of drug administered to males was 0.44 (0.06) mg/kg and to females 0.48 (0.08) mg/kg, and the mean (sd) duration times were 14.9 (4.5) minutes and 16.1 (5.3) minutes. The mean (sd) time taken to recover from immobilisation was 14.5 (4.6) minutes for males and 15.7 (5.3) minutes for females. Physiological condition and size significantly affected the duration of anaesthesia. Thin seals remained immobilised for 18 (7) minutes whereas fatter seals remained immobilised for 15 (4) minutes (P<0.0001).

Anesthetics, Dissociative↗