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Biomedical subjects

I D Smith

Publications and source records attributed to I D Smith.

At least 19 recordsLinked to original sources

Hair analysis: self-reported use of "speed" and "ecstasy" compared with laboratory findings.

Drug use histories were collected from 100 subjects recruited from the "dance scene" in and around Glasgow, Scotland. In addition, each subject donated a hair sample which was analyzed by gas chromatography/mass spectrometry (GC/MS) for amphetamine (AP), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MD MA) and 3,4-methylenedioxyethylamphetamine (MDEA). The hair samples were analyzed in two 6 cm segments or in full, ranging from 1.5 to 12 cm depending on the length of the hair. Approximately 10 mg of hair was ground to a fine powder before treatment with beta-glucuronidase/aryl sulfatase. A solid-phase extraction procedure was carried out followed by derivatization with pentafluoropropionic anhydride (PFPA). All extracts were analyzed by gas chromatography/mass spectrometry (GC/MS). Of the 139 segments analyzed, 77 (52.5%) were positive for at least one of the five amphetamines. The drug concentrations found in the hair were compared with the self-reported drug histories. A concordance of greater than 50% was found between the self-report data and levels detected in hair. However, no correlation was found between the reported number of "ecstasy" tablets consumed and the drug levels detected in hair. An increase in the average drug levels measured was observed from low to high use (number of "ecstasy" tablets/month). A large number of false negatives and a low number of false positives were observed.

Adolescent↗

Rotational bias in intact rats following intrastriatal injections of dopaminergic drugs.

Following unilateral 6-OHDA lesions of the striatum, systemic dopamine agonists produce rotation due to receptor supersensitivity. Rotation following intrastriatal dopamine agonists in intact rats also has been reported, although these studies are few and contradictory. Dorsal striatal injection (0.5 microl) of the direct dopamine agonist apomorphine failed to caused rotation. In addition, neither the D1 agonist SKF 81297, the cAMP analogue Sp-cAMPS, nor the D2 agonist quinpirole affected rotation. In contrast, the dopamine releaser amphetamine (1.1, 10.9, 108.7 mM) caused significant contralateral rotation. This effect was reversed by coinjection of the D1 antagonist SCH 23390 (3.1 mM) but not by the D2 antagonist eticlopride. Rotation was also reversed by TTX coinjections (100 microM) but not by the NMDA antagonist AP7 or the kainate/AMPA antagonist CNQX. Thus, direct dopamine agonists in the striatum failed to cause behavioral asymmetry, whereas amphetamine induced contralateral rotation. This effect is mediated primarily by D1 receptors and requires concurrent neuronal activation that appears to be independent of glutamate receptor stimulation. These results are consistent with studies of Fos induction in normosensitive animals following dopamine agonists and are discussed in terms of changes in basal ganglia output pathway activity.

Animals↗

Glutamate receptor agonist injections into the dorsal striatum cause contralateral turning in the rat: involvement of kainate and AMPA receptors.

Unilateral stimulation of glutamate receptors in the dorsal striatum of intact rats resulted in contralateral turning. Turning behavior was recorded for 20 min following unilateral intrastriatal injections (0.5 microliter) in chronically cannulated rats. Kainate injections caused a dose-dependent increase in contralateral rotation that was blocked by the glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), the action potential blocker tetrodotoxin, and by increasing doses of the dopamine receptor antagonist cis-flupenthixol. Injections of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) also caused rotation that was blocked with co-injections of CNQX, tetrodotoxin or cis-flupenthixol. Neither CNQX nor tetrodotoxin injected alone caused turning. This effect is dopamine-dependent, and may result from a kainate or AMPA-induced increase in dopamine release. Glutamate receptor agonist injections into the striatum may cause contralateral turning by degrading information in ascending cortical projections and may further influence locomotion via basal ganglia output nuclei projections to the brainstem.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

The neurochemical pathology of thiamine deficiency: GABAA and glutamateNMDA receptor binding sites in a goat model.

Synaptic plasma membranes were prepared from four cerebrocortical areas from six male Angora goats made chronically thiamine deficient (TD) by the administration of AmproliumTM (600-900 mg/kg daily for 38-44 d). Four male controls were matched for age (27-30 mo). Four different radioligands were used to characterise GABAA and Glu-RNMDA receptor binding sites. There were marked, localised and contrasting changes in motor cortex, with an increase in GABAA and a decrease in Glu-RNMDA binding site densities. Less clearcut changes of a similar nature were seen in visual cortex. There was no variation in the parameters of GABA-activated [3H]diazepam binding between cortical areas in control goats, but there was a reduction in the maximal response to GABA in all areas in TD goats. There were regional variations in glutamate-activated [3H]MK-801 binding in control goat brain, and a non-selectively reduced maximal response in TD. Alterations in these indices of GABA- and glutamate-mediated neurotransmission may underlie the neurological signs of acute thiamine deficiency in these animals.

Alcoholism↗

Contralateral turning caused by metabotropic glutamate receptor stimulation in the dorsal striatum is reversed by MCPG, TTX, and cis-flupenthixol.

Recent evidence suggests an involvement of metabotropic glutamate receptors in the physiology of the striatum. In this study, rotation was recorded in an automated rotometer for 20 min following dorsal striatal injections (0.5 microliter) in cannulated rats. The metabotropic agonist 1-aminocyclopentane-trans-1, 3-dicarboxylic acid (1S,3R-ACPD) caused dose-dependent contralateral rotation. Turning caused by 500 microM 1S,3R-ACPD was reversed by coinjections of the metabotropic antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG, 1 mM) and by tetrodotoxin (100 microM). Injections of MCPG alone (10 microM, 100 microM, 1 mM) failed to elicit turning. Increasing doses of the dopamine antagonist cis-flupenthixol also reversed 1S,3R-ACPD-induced rotation. Thus unilateral striatal metabotropic glutamate receptor stimulation can cause receptor-specific rotation that may result from an increase in neural activity, and is dependent on intact dopamine neurotransmission.

Animals↗

Caesarean section in chronic renal failure.

A 22-year-old woman presented for Caesarean section at 34 weeks' gestation. She had chronic renal failure, with a glomerular filtration rate of 14 mL min-1 and was treated with twice weekly dialysis. We describe the potential problems of the case including cardiovascular instability, fluid balance and some of the effects of uraemia. We also describe the anaesthetic management of the case.

Adult↗

Pharmacokinetics of flumazenil and midazolam.

We have studied simultaneously the pharmacokinetics of flumazenil and midazolam in 12 healthy Chinese children, aged 5-9 yr, undergoing circumcision. Two hours before operation each patient received midazolam 0.5 mg kg-1 orally for premedication and 0.5 mg kg-1 i.v. during induction. Six minutes after cessation of anaesthesia, a bolus of flumazenil 10 micrograms kg-1 was given i.v., followed by an infusion of flumazenil at 5 micrograms kg-1 min-1 which was maintained until the child could identify himself. Midazolam data were consistent with a three-compartment model with a mean (SD) elimination half-life of 107 (30) min, total body clearance of 15.4 (3.2) ml min-1 kg-1 and apparent volume of distribution at steady state of 1.9 (0.6) litre kg-1. Flumazenil data were best interpreted by a monoexponential function, with a mean terminal elimination half-life of 35.3 (13.8) min, a total plasma clearance of 20.6 (6.9) ml min-1 kg-1 and apparent volume of distribution at steady state of 1.0 (0.2) litre kg-1. No unchanged midazolam was detected in the 24-h urine sample, but 5.8-13.8% of the flumazenil dose was recovered unchanged. At the time of self identification, 4.5 (1.4) min after flumazenil administration, the mean plasma concentrations of midazolam and flumazenil were 163.1 (43.7) and 29.9 (16.1) ng ml-1, respectively.

Child↗

Determination of topanol antioxidants in methacrylates using capillary gas-liquid chromatography.

This paper presents a method to identify and determine topanol A and topanol O antioxidants in methylmethacrylate and 11-bromoundecylmethacrylate. The method is both simple and rapid. Analysis is performed on a 10 m x 0.53 mm I.D. HP-1 capillary gas chromatography column with a temperature gradient and a high carrier gas flow-rate (16.5 ml/min). Quantitation is by internal standardisation. Validation of the method is described for both topanols at concentrations of approximately 50 ppm in methylmethacrylate and 250 ppm in 11-bromoundecylmethacrylate.

Antioxidants↗

Role of the subthalamic nucleus in the regulation of nigral dopamine neuron activity.

The influence of subthalamic nucleus (STN) afferents on dopaminergic (DA) neurons of the rat substantia nigra (SN) was investigated. Hemisections of the brain placed between the STN and the SN or located anterior to the STN caused an increase in the firing rate of DA cells without producing significant changes in their firing pattern. In contrast, electrolytic and ibotenic acid lesions of the STN resulted in 93% and 49% reductions, respectively, in the level of burst firing without affecting the firing rate of DA cells recorded in the lateral SN. Furthermore, procedures which interrupted the STN input to the SN produced rapid pacemaker-like firing in 18% of the lateral SN DA neurons recorded. Activation of the STN using single pulses of electrical stimulation caused: 1) a 20-50 msec inhibition of DA cell firing followed by an excitation, which in 35% of DA cells was accompanied by spikes occurring in a burst-like pattern, and 2) a short-latency inhibition lasting 5-25 msec in 75% of non-DA SN zona reticulata (ZR) neurons. On the other hand, stimulation of the STN for 1 minute at 20 Hz resulted in an initial decrease in DA cell burst firing followed by elevated firing rates and increased burst firing by 30-60 minutes after the stimulation. Pharmacological activation of the STN by infusion of bicuculline caused a rapid inhibition of DA cells followed by a two-fold increase in burst firing 6-14 minutes later, whereas SN ZR cells responded with an elevation in firing rate which dissipated in 6-14 minutes. Muscimol-induced STN inhibition produced complimentary biphasic changes in SN neuron firing: 1) an initial increase followed by a decrease in burst firing and firing rate of DA neurons and 2) a rapid inhibition followed by an excitation of ZR cells over a similar time course. Thus, the STN appears to exert a dual action on SN DA cells: 1) initial inhibition possibly mediated through STN excitation of the inhibitory SN ZR projections to DA cells, and 2) a facilitation of burst firing which may be a direct effect of excitatory STN afferents.

Animals↗

The upgraded Finapres 2300e. A clinical evaluation of a continuous noninvasive blood pressure monitor.

Measurements from the upgraded Finapres 2300e continuous noninvasive blood pressure monitor, the Finapres 2300 and Colin oscillometric noninvasive blood pressure monitor were compared with invasive arterial line blood pressure readings. Fifteen young Chinese patients undergoing elective spinal surgery of more than 2 h duration had contemporaneous blood pressure measurements digitally recorded every minute. Data were analysed using methods described by Bland and Altman to assess agreement of noninvasive devices with an arterial line. Results showed that although the Finapres 2300e was significantly more accurate than the Finapres 2300 and Colin noninvasive blood pressure monitors it could not be recommended as a substitute for continuous arterial line blood pressure monitoring. Both Finapres devices demonstrated reductions in accuracy related to time (drift) and over-read diastolic and mean pressures by 5-8 mmHg throughout the range of mean arterial line pressures (bias). The Colin was consistently less accurate than the Finapress monitors and performed worst at low mean arterial line pressures.

Adolescent↗

An evaluation of prolonged oximetric data acquisition.

Data derived from pulse oximetry has inherent limitations, one of which is artifactual desaturation caused by patient movement. Perioperative patterns of oxygen desaturation were studied for a mean duration of 67 hours in eight young patients following corrective spinal surgery. Pulse oximetry data were relayed to a computer using Satmaster, a program which permits storage, retrieval, signal evaluation and statistical analysis of oximetry data. Desaturation episodes were mild, of short duration and their infrequent occurrence was not increased during intravenous morphine infusion. Retrospective identification of contemporaneous artifactual changes in signal amplitude permitted the removal of artifactual desaturations from our statistical data analysis. This decreased the average time desaturated from 5.4% (220 minutes) to 4.2% (162 minutes) of the monitored period representing a 25% reduction in absolute incidence and a 35% reduction in episodic incidence of desaturation. Acquired data should be validated and inferences drawn from non-validated data must be assessed with caution.

Adolescent↗

Diamorphine analgesia after caesarean section. Comparison of intramuscular and epidural administration of four dose regimens.

In a randomised double-blind study, the efficacy, duration of action and side effects of five diamorphine analgesia regimens following Caesarean section are described. The time to next analgesia was shorter in the 5 mg intramuscular group (3.53 hours) than in any of the four epidural groups: 5 mg (5.7 hours, p = 0.007), 2.5 mg (4.76 hours, p = 0.103), 5 mg with adrenaline 1/200,000 (7.2 hours, p = 0.001) and 2.5 mg with adrenaline 1/200,000 (6.05 hours, p = 0.007). Multiple regression analysis showed that the addition of adrenaline significantly increased the duration of action of epidural diamorphine (p less than 0.05). The 5 mg dose with adrenaline showed no advantage when compared with 2.5 mg with adrenaline (p = 0.16). No serious side effects were reported in any group.

Adolescent↗

Direction-selective responses of units in the dorsal terminal nucleus of cat following intravitreal injections of bicuculline.

Extracellular recordings from single units in the dorsal terminal nucleus (DTN) of the cat accessory optic system (AOS) were made before and after intravitreal injections of the GABA antagonist bicuculline methiodide (BMI). Direction-selective responses of DTN cells elicited through the contralateral, injected eye were abolished 7-12 h following the injection. For the concentrations tested, direction-selective responses through the contralateral (injected) eye did not recover within 26 h. Direction-selective responses through stimulation of the ipsilateral (uninjected) eye were also dramatically depressed for 1-9 h after contralateral eye injections. However, direction-selective responses through the ipsilateral eye eventually returned and were often more vigorous in the final stages. BMI injections into the ipsilateral eye failed to block direction-selective responses through the ipsilateral eye. The effects of intravitreal BMI on contralateral eye responses imply that DTN units receive input from direction-selective retinal ganglion cells. In addition, these results suggest that direction-selective input to the DTN from the visual cortex is independent of the retinal pathway. Using pharmacological methods described here, for the first time direction-selective responses of AOS units driven through the ipsilateral eye can be experimentally isolated.

Animals↗

Rapid identification of antibiotic-resistant corynebacteria with the API 20S system.

The API 20S system (Analytab Products, Plainview, N.Y.) was evaluated for the rapid identification of multiply antibiotic-resistant aerobic diphtheroids. Sixty-eight clinical isolates of multiply resistant Centers for Disease Control group JK and group D2 corynebacteria had API 20S profiles which were clearly different from those of a number of strains of other Corynebacterium species which were tested. The API 20S system allowed more rapid identification of antibiotic-resistant diphtheroids than conventional biochemical tests. Its use for corynebacteria other than group JK and group D2 is not recommended at this time.

Anti-Bacterial Agents↗

Prostaglandin F2 alpha-induced prolactin release and luteolysis in the goat.

Injection of prostaglandin F2 alpha (PGF2 alpha) initiated a significant increase in plasma prolactin levels in all goats except those in anoestrus. Luteolysis occurred in non-pregnant goats during the mid luteal phase when the goats were given PGF2 alpha either with or without the suppression of prolactin release by bromocryptine (CB154). Luteolysis and subsequent parturition also occurred in pregnant goats in mid and late gestation after PGF2 alpha injection, with an associated release of prolactin and decrease in plasma progesterone. Acute prolactin release in response to injection of thyrotrophin releasing factor may have had a transient effect on plasma progesterone levels, but did not appear to be luteolytic in either pregnant or non-pregnant goats.

Anestrus↗