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Biomedical subjects

S McLean

Publications and source records attributed to S McLean.

At least 127 records · Page 7Linked to original sources
PubMed1987

Assessing dementia. Part I: Difficulties, definitions and differential diagnosis.

Despite the pressures of an increasingly ageing population and an ever increasing scientific knowledge, the clinical characteristics of dementia remain poorly defined. This relative lack of clarity in clinical understanding has led to diverse diagnostic problems, including those of mistaken diagnosis as well as over- and under-diagnosis in different settings. This paper focuses on the syndromal and aetiological diagnosis of dementia by outlining current clinical definitions, considering differential diagnosis in detail and reviewing characteristics of common dementing disorders. The past emphasis on a search for treatable causes, the reliance on laboratory investigations and the concept of subcortical dementia are all questioned. Aspects of evaluation that are stressed include the value of brief objective cognitive testing, a knowledge of normal age-related cognitive changes, flexible criteria for Alzheimer's disease and a comprehensive individualised evaluation of the person. Broader assessment issues will be dealt with in a second paper.

Aged↗
PubMed1986

Autoradiographic localization of mu- and delta-opiate receptors in the forebrain of the rat.

The autoradiographic distributions of mu opiate receptors, labeled in vitro by [125I]D-Ala2-MePhe4-Met(o)5-ol-enkephalin (FK), and delta-opiate receptors, labeled by [3H]D-Ala2-D-Leu5-enkephalin (DADLE) in the presence of oxymorphone to block high affinity binding to the mu site, were examined and compared in the forebrain of the rat. The mu- and delta-receptors were differentially distributed in most structures. mu Binding sites were found in nearly all gray matter structures and showed heterogeneous patterns of density that were correlated with cytoarchitecture and neuronal connections. Laminar density profiles were seen in laminated structures such as olfactory bulb, cerebral cortex and hippocampus. Highest mu binding densities were in striatal patches and the habenular streak. delta Sites had distinct laminar patterns in the main olfactory bulb and cortex which differed from the mu patterns. The external plexiform layer of the main olfactory bulb had the greatest density of delta binding sites; cortex and striatum were also densely labeled. The septum, globus pallidus, preoptic area and hypothalamus were lightly labeled by both ligands. The magnocellular hypothalamic nuclei had negligible mu and delta labeling. The thalamus had dense mu but sparse delta sites. mu And delta binding sites were both present in the amygdala but had different distributions. Two fiber tracts--optic tract and fasciculus retroflexus--had FK labeling. In contrast, a portion of the corpus callosum was labeled by DADLE and not by FK. The results suggest an association of mu-opiate receptors with sensory, especially olfactory, and limbic projections in the forebrain, and delta-opiate receptors with intrinsic and commissural forebrain pathways.

Amygdala↗
PubMed1986

The localization and characterization of substance P and substance K in striatonigral neurons.

Specific substance P and substance K radioimmunoassays coupled to high-performance liquid chromatography were used to characterize striatal and nigral tachykinin immunoreactivity. Using these assays, authentic substance P and substance K accounted for nearly all substance P and substance K immunoreactivity, respectively. A series of coronal knife cuts of the striatum caused parallel depletions in nigral substance P and substance K, consistent with the possible colocalization of these tachykinins in striatonigral neurons.

Animals↗
PubMed1986

The pharmacokinetics of tetrabenazine and its hydroxy metabolite in patients treated for involuntary movement disorders.

The pharmacokinetics of tetrabenazine and a metabolite, hydroxytetrabenazine, have been investigated in seven patients being treated for involuntary movement disorders. Tetrabenazine had a very low oral systemic availability (mean 0.049 +/- 0.032 SD). First-pass metabolism to hydroxytetrabenazine was extensive, and the systemic availability for this metabolite was high (mean 0.81 +/- 0.30 SD). Since hydroxytetrabenazine has been reported to be as active as tetrabenazine in depleting brain amines, and is present at much higher plasma concentrations than the parent drug, it is likely that this metabolite is the more important therapeutic moiety.

Blood Proteins↗
PubMed1986

1,3-Di(2-[5-3H]tolyl)guanidine: a selective ligand that labels sigma-type receptors for psychotomimetic opiates and antipsychotic drugs.

Brain sigma-type receptors are thought to mediate hallucinogenic effects of certain benzomorphan opiates in humans. The biochemical characterization of sigma receptors has been difficult because of the lack of potent and selective ligands. We report here the synthesis and characterization of a tritiated, symmetrically substituted guanidine derivative, 1,3-di(2-[5-3H]tolyl)guanidine ([3H]Tol2Gdn), that binds with high affinity to a single population of binding sites in guinea pig brain membrane preparations. The [3H]Tol2Gdn binding site displays stereoselectivity for dextrorotatory optical isomers of benzomorphan opiates known to have sigma-type behavioral effects. Furthermore, the [3H]Tol2Gdn binding site has a high affinity for haloperidol and for phenothiazine antipsychotics, which have antihallucinatory properties in humans. The drug-selectivity profile of [3H]Tol2Gdn binding closely correlates with the drug-selectivity profile of tritiated (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [+)-[3H]3-PPP) binding to guinea pig brain membrane receptors. (+)-[3H]3-PPP has been proposed to be a selective sigma-receptor ligand [Largent, B. L., Gundlach, A. L. & Snyder, S. H. (1984) Proc. Natl. Acad. Sci. USA 82, 4983-4987]. Receptor autoradiography using [3H]Tol2Gdn on slide-mounted rat and guinea pig brain sections reveals a heterogeneous distribution pattern of enriched binding in limbic and sensorimotor structures of the brain. These results indicate that [3H]Tol2Gdn is a selective ligand for the sigma-site. Availability of this sigma-receptor probe should greatly facilitate the physiological, biochemical, and pharmacological characterization of sigma receptors in brain.

Animals↗
PubMed1985

Comparison of the substance P- and dynorphin-containing projections to the substantia nigra: a radioimmunocytochemical and biochemical study.

A series of knife cuts were made in the striatonigral pathway and changes in dynorphin B (Dyn) and substance P (SP) input to the substantia nigra were examined using radiolabeled antibodies and radioimmunoassay (RIA). Cryostat cut sections were incubated with primary antibody followed by a secondary antibody labeled with 125I. Apposition of the radiolabeled sections to LKB Ultrofilm generated an image that was qualified by computerized optical densitometry. The striatonigral system served as a model system for comparing the quantitative capabilities of radioimmunocytochemistry with RIA. The results indicated a strong correlation between optical densitometry measurements and RIA for both Dyn (r = 0.97) and SP (r = 0.98) antisera. This suggests that radioimmunocytochemistry may be used for quantitative, as well as, qualitative descriptions of the distribution of tissue antigens. Knife cuts separating the rostral caudate putamen from the substantia nigra resulted in less than 40% depletion of dynorphin and substance P in the nigra pars reticulata, leaving the levels of both peptides relatively unchanged in the pars lateralis. More caudal knife cuts resulted in progressively greater depletions of both peptides in the pars reticulata and pars lateralis.

Animals↗
PubMed1985

Value of hepatic computerized tomographic scanning during amiodarone therapy.

Amiodarone therapy is difficult to monitor because of the poor correlation between plasma amiodarone levels and clinical efficacy or toxicity. Monitoring tissue levels may give a better measure of effectiveness, but tissue levels cannot be easily measured. The iodine-containing amiodarone and its major metabolite, desethylamiodarone (DA), are highly tissue-bound, and it has been shown that computerized tomographic (CT) scanning of the abdomen will detect drug deposition in the liver. Ten patients receiving chronic amiodarone therapy were studied by abdominal CT scanning. Liver CT density was increased in 6; 68 to 94 CT units (normal 50 to 65) and liver/spleen relative CT density increased in 5; 1.4 to 2.0 (normal 1.0 to 1.3). Estimates of liver drug levels (based on a calibration curve with inorganic iodide) gave values of up to 3 g of amiodarone and DA per kilogram weight of liver. Absolute and relative liver CT density correlated significantly with plasma levels of DA (r = 0.65, p less than 0.05), but not with amiodarone (r = 0.55, p less than 0.1). No significant correlation was found with QTc intervals. This indirect estimate of liver deposition of amiodarone and DA may prove useful in guiding antiarrhythmic therapy.

Aged↗
PubMed1985

Food does not affect the bioavailability of baclofen.

It is recommended that baclofen, a centrally acting muscle relaxant, be administered with food or milk to minimize its gastrointestinal side-effects. However, there are no published data on the influence of food on the bioavailability of the drug. The extent and rate of absorption of baclofen were investigated after the oral administration of single 20-mg doses to five healthy volunteers. The drug was administered either under fasting conditions or with a standard meal, according to a crossover design. Food did not significantly influence either the rate or the relative extent of absorption of baclofen. Therefore, it is unlikely that the administration of baclofen with food to reduce the likelihood of gastrointestinal toxicity will adversely affect the clinical response to the drug.

Adult↗
PubMed1985

Comparison of substance P and enkephalin distribution in rat brain: an overview using radioimmunocytochemistry.

The distribution of substance P and leucine enkephalin in mid- and fore-brain areas of the rat was studied using a radioimmunocytochemical method. The secondary antibody was labeled with 125I and the sections apposed to LKB Ultrofilm or emulsion-dipped. In alternate sections an extensive distribution of substance P and enkephalin immunoreactive material was seen in frontal, cingulate, retrosplenial, and entorhinal cortices. Substance P and enkephalin exhibited a remarkable overlap in many of these cortical areas as well as in the nucleus accumbens, caudate, portions of the hypothalamus, amygdala, thalamus and central gray. Differences in distribution were seen in the retrosplenial cortex, septum, ventromedial hypothalamus, hippocampus, the substantia nigra and the superior colliculus. The results provide a detailed immunohistochemical demonstration of the laminar patterns of substance P and enkephalin in the cortex of the rat. The results are discussed in terms of the interaction of substance P and enkephalin. The matches and mismatches of immunoreactive substance P and enkephalin and the locations of their receptors are also examined.

Animals↗
PubMed1985

Audit of a monitoring service for free phenytoin.

This study assessed the value of introducing the measurement of free phenytoin levels in a public hospital. After publicising the availability and purpose of the assay, free phenytoin levels were determined either (a) on the doctor's request or (b) when the total level was requested and the patient's record showed evidence of factors predisposing to an elevated unbound fraction. Total phenytoin was measured by EMIT, and the unbound fraction by ultrafiltration at 37 degrees C using [14C]-phenytoin as a tracer. During a 9 month period, 70 free level determinations were performed on 46 patients. These comprised 20% of all phenytoin assays. The median free phenytoin fraction was 13.6% (range 9.3-28.6%). While total phenytoin levels were below the normal optimum range in 61% cases, free levels were probably therapeutic or above in 70% cases. Dosage adjustments were recommended on the basis of the free level, and were followed more often when the doctor had requested the free level assay (P less than 0.05). The results suggest that a free phenytoin level assay can improve the usefulness of therapeutic drug monitoring, particularly when the doctor understands the purpose of the assay.

Adolescent↗
PubMed1985

Formation of reactive metabolites of phenacetin in humans and rats.

The metabolism of phenacetin to reactive intermediates in humans was estimated from the excretion of thio adducts in urine. N-Hydroxyphenacetin, a precursor of reactive metabolites, was also quantified. Following an oral dose of phenacetin (10 mg/kg) to humans, these metabolites in 24 h urine were: paracetamol-3-cysteine, 4.4% dose; paracetamol-3-mercapturate, 3.9%; 3-thiomethylparacetamol, 0.4%; N-hydroxyphenacetin, 0.5%. Rats showed a considerable increase in N-hydroxyphenacetin excretion after chronic dosing with phenacetin at high dosage (500 mg/kg) for one month. chronic dosing with a low dose (50 mg/kg) did not increase N-hydroxyphenacetin excretion, but a marked increase occurred on concomitant administration of aspirin and caffeine.

Adult↗
PubMed1984

Mass spectrometric determination of N-hydroxyphenacetin in urine using multiple metastable peak monitoring following thin-layer chromatography.

This work describes a method for the quantitative determination of the labile, toxic N-hydroxy metabolite of phenacetin in urine. A thin-layer chromatography step was used for the preliminary purification of extracts, and the specificity of the assay was based on the monitoring of specific metastable decompositions in a forward geometry double-focussing mass spectrometer, in a manner analogous to conventional tandem mass spectrometry. This precluded the need for a gas chromatographic separation, thus minimizing thermal decomposition which can occur with these compounds, as well as enabling very rapid analyses.

Chromatography, Thin Layer↗
PubMed1984

Determinants of patient compliance, control, presence of complications, and handicap in non-insulin-dependent diabetes.

Factors affecting patient compliance with diet and medication, clinical control, complications, and handicap were studied in 114 subjects with non-insulin-dependent diabetes mellitus who were attending a hospital diabetic clinic. Compliance with diet and hypoglycemic medication was correlated. The perceived importance, and the ease of compliance were the principal correlates of patient compliance. Factors independently related to diabetic control were compliance with diet, and the quality of the patient's diet. Diabetes which was poorly controlled, and which was of several-years' standing, was more likely to involve complications. Both poor control and the presence of complications contributed to handicap. Increased dietary education and counselling, with emphasis placed on the importance and benefits of compliance with prescribed diets, may improve control, decrease the incidence of complications, and ultimately minimise handicap due to diabetes in non-insulin-dependent patients.

Adult↗
PubMed1984

A randomised trial of strategies to improve patient compliance with anticonvulsant therapy.

Fifty-three hospital outpatients with epilepsy were randomly allocated to either a control or an intervention group. Patients in the intervention group were subjected to a combination of compliance-improving strategies: patient counselling, a special medication container, self-recording of medication intake and seizures, and mailed reminders to collect prescription refills and attend clinic appointments. Compliance with anticonvulsant therapy (as measured by plasma anticonvulsant levels and prescription refill frequencies), and seizure frequency, were evaluated in each patient prior to intervention and 6 months afterwards. Patient compliance and clinical control improved significantly in the intervention group patients. Seizure frequency was, on average, halved following intervention. Compliance and seizure frequency were unaltered in the control group. Intervention failed to improve clinic appointment keeping. Poor compliance with drug therapy commonly confounds the treatment of epilepsy. This study shows that compliance can be improved and seizure frequency lessened by strategies that are easily incorporated into the routine management of epileptic patients.

Adolescent↗
PubMed1983

Opiatergic projection from the bed nucleus to the habenula: demonstration by a novel radioimmunohistochemical method.

In a modification of the indirect immunohistochemical method 125I-labeled secondary antibodies were used to autoradiographically visualize enkephalin-like immunoreactivity. Electrolytic lesions of the bed nucleus of the stria terminalis (BNST) resulted in a decrease in enkephalin-like immunoreactivity in the ipsilateral habenula. This suggests an opiatergic pathway originating in the BNST and projecting to the habenula. In addition, the value of the radioimmunohistochemical technique is discussed.

Animals↗
PubMed1983

Acetylation of sulphanilamide in four marsupials and a monotreme.

1. The urinary metabolites of sulphanilamide (100 mg/kg, i.p.) have been studied in four marsupials (the Tasmanian devil, brushtail possum, pademelon and barred bandicoot), a monotreme (the echidna) and a eutherian (the rat). 2. All species excreted some unchanged sulphanilamide (20-30% of dose in 24 h). The major urinary metabolite in the devil, possum and pademelon was N4-acetylsulphanilamide (6-17%). This was less than that excreted by the rat (40%). These three marsupials and the rat also excreted small amounts of N1-acetyl and N1, N4-diacetylsulphanilamide. 3. The bandicoot and echidna were virtually unable to acetylate sulphanilamide, unlike the 16 other species of animals and birds in which this has been studied. The reason for this metabolic defect is unknown.

Acetylation↗