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Biomedical subjects

S Guthrie

Publications and source records attributed to S Guthrie.

At least 73 records · Page 4Linked to original sources

Subcellular localization of triphenylethylene antiestrogen binding sites (TABS) in rat liver.

The subcellular distribution of triphenylethylene anti-estrogen binding sites (TABS) was examined in the rat liver. Nuclear, mitochondrial and microsomal fractions were prepared by differential centrifugation, extracted with 0.5 M KCl and bound [3H]tamoxifen was determined by the dextran coated charcoal method. The relative concentration of TABS in each fractions were: nuclear 30.2; mitochondrial, 14.8 and microsomal, 10.2 pmol/g tissues. No TABS were detected in the high speed cytosol. The dissociation constants of nuclear and mitochondrial TABS were similar (1-2 nM); however, a higher number was obtained for microsomal TABS (5-6 mM). The ability of other triphenylethylene drugs to compete for [3H]tamoxifen binding to TABS was similar to tamoxifen for mitochondrial and microsomal sites. In contrast, nafoxidine was a more potent inhibitory for nuclear TABS. Exposure of high salt nuclear extracts to charcoal prior to assay did not reveal any evidence for an endogenous ligand of high affinity. We conclude that TABS are present in nuclear, mitochondrial and microsomal fractions of rat liver and that the nuclear fraction contains the highest concentration of these sites.

Animals↗

Clinical studies on norepinephrine metabolism: how to interpret the numbers.

Metabolism, synthesis rates, and pharmacokinetics of major metabolites of endogenous norepinephrine were investigated in 38 drug-free depressed patients receiving a low monoamine diet on a closed ward. In a group of 21 patients, plasma and cerebrospinal fluid (CSF) concentrations of 3-methoxy-4-hydroxyphenyl-glycol (MHPG) correlated positively, but not significantly. In two groups of eight patients each, effects of desipramine and zimelidine on the central production rate of MHPG were examined using CSF and urine data. Both desipramine and zimelidine significantly reduced the central production rate of MHPG.

Adult↗

An in-vitro morphological study of Q-switched neodymium/YAG laser trabeculotomy.

Laser trabeculotomies produced by directing a pulsed neodymium/YAG laser beam at specimens of human anterior chamber angle obtained post mortem or after enucleation were studied by light microscopy and by scanning and transmission electron microscopy to assess the dimensions of the openings created in the trabecular meshwork, their penetrance to the canal of Schlemm, and the extent or absence of laser induced cellular damage in immediately adjacent tissue. A pulse duration of 40-50 ns at energy levels of around 30 mJ was used and the laser cavity carefully tuned to give a Gaussian spatial mode pattern. Openings in the trabecular meshwork typically of 100 microns in diameter and penetrating through to the canal of Schlemm could be regularly created with only minimal damage to adjacent tissue as judged by transmission electron microscopy. The information so gained may be useful in determining the parameters required for successful laser trabeculotomy as a treatment for primary open-angle glaucoma.

Aged↗

Effects of alcohol and other psychotropic drugs on eye movements: relevance to traffic safety.

The effects of alcohol and other psychotropic drugs on eye movements are reviewed with particular attention to the possible relevance of these effects for traffic safety. Alcohol has been shown to have diverse effects, including reduction of the velocity of both saccadic and smooth pursuit eye movements, increased saccadic latency, impairment of convergence and induction of nystagmus. These effects probably contribute to impaired visual information processing, which reduces driving ability. Barbiturates have been reported to produce effects similar to alcohol, and the effects of benzodiazepines and opioids seem to be more limited but still substantial. Marihuana has relatively little effect on eye movements.

Accidents, Traffic↗

Effects of buspirone and diazepam, alone and in combination with alcohol, on skilled performance and evoked potentials.

Effects of buspirone, 10 and 20 mg, and diazepam, 10 mg, on skilled performance and evoked responses, as well as their interactions with 0.8 g/kg of alcohol were investigated in 24 healthy men. Alcohol, 0.8 g/kg, caused the greatest performance impairment, followed closely by diazepam. Both doses of buspirone had lesser effects. Buspirone had primarily sedative effects which were short lasting, whereas diazepam impaired tracking and body balance in addition to being sedative. Both anxiolytics showed only slight additive interactions with the present dose of alcohol. A strong drug effect and a lesser but significant alcohol and a drug/alcohol interaction effect were seen on evoked potentials. Diazepam effects on evoked potentials were similar to alcohol, whereas buspirone in some instances appeared to reverse the alcohol effect. Pharmacokinetics of buspirone and diazepam were not significantly affected by concomitant administration of alcohol. The psychomotor side effect profile of a single anxiolytic dose of buspirone is preferable to a single 10-mg dose of diazepam.

Adult↗

In vitro studies with a pulsed neodymium/YAG laser.

The relationships between the destructive effects of Q-switched Nd/YAG laser pulses and a number of experimental parameters were studied for various target materials including in particular excised, fixed samples of human trabecular meshwork. The laser parameters altered were the pulse energy, the convergence angle of the focused beam, and the position of the focus of the beam relative to the target's axial position. The main finding was that it was possible to make deep holes, of a diameter less than 100 micron, in virtually transparent samples of trabecular meshwork with a laser delivery system of 6 degrees convergence and pulse energies of 14 mJ or more. The relevance of this and the other experimental results to the development of a reliable system for performing internal trabeculotomies for the treatment of open-angle glaucoma is presented.

Cornea↗

Thermal lens measurements in the cornea.

Q-switched pulses from a neodymium/YAG (yttrium-aluminium-garnet) laser were passed through corneal discs taken from the enucleated eyes of three baboons and four rabbits. The time course of heat dissipation following absorption of laser energy by the tissue was studied with the use of a second continuous wave laser beam acting as a probe. It was found that the absorption of each neodymium/YAG pulse created a transient divergent lens within the cornea as theoretical considerations predicted. The relaxation time that characterised the decay of this thermal lens for a 1/e laser beam diameter of 2.0 mm was found to be 2.3 +/- 0.1 s (mean +/- standard error for 12 separate groups of measurements). Our results show that Q-switched laser pulses passing through apparently unaffected transparent tissues can induce thermal lens effects which persist for several seconds. The optical transfer of each pulse in a stream will be identical only if enough time is left between pulses for the tissues to return to their initial state. Therefore, when such laser pulses sharply focused to perform high precision intraocular surgery are used, thermal lensing in the transparent ocular media must limit the rate at which pulses can be usefully delivered.

Animals↗

Interaction between antidepressants and perphenazine in psychiatric inpatients.

In a study of 99 patients receiving amitriptyline or nortriptyline alone and 60 patients receiving one of these antidepressants in combination with perphenazine, the patients receiving the combination medication had up to 70% higher antidepressant plasma levels than patients receiving the antidepressant alone. The groups did not differ significantly in sex, age, smoking behavior, or antidepressant dose level. Due to the possibility of side effects from such combination medication, the authors recommend that depressed patients not responding to the tertiary amine tricyclic antidepressants receive a trial of high doses of the drugs before antidepressant-neuroleptic combinations are administered.

Adult↗

The cohesiveness of alcoholism-complicated marriages and its influence on treatment outcome.

One-hundred husbands, diagnosed as suffering from alcoholism, and their wives, were followed up twelve months after initial consultation and assessment. Follow-up information was complete in 89 cases. On the basis of both husband and wife accounts of the husband's drinking behaviour during the follow-up period, and their assessment of the drinking problem at twelve-months follow-up, 28 were classified as having a 'good' outcome and 29 as having a 'bad' outcome. In the remaining 32 cases outcome was considered 'equivocal'. A composite measure of marital cohesion was predictive of twelve-month outcome classification, cohesive marriages being significantly more likely to have a good outcome. The measure of marital cohesion was based upon husband and wife reports of mutual affection and of husband involvement in family tasks, favourable spouse perceptions and meta-perceptions, and optimism about the future of the marriage. Composite measures of dominance balance within the marriage were not predictive of outcome. Husband's job status, husband's self-esteem, and wife's reported hardship were not independent of marital cohesion, and were themseleves predictive of twelve-months outcome. When these variables were partially controlled it was found that marital cohesion remained predictive for husbands with relatively low status jobs and husbands with relatively low levels of self-esteem. It is an over-simplification to state that either the marriage, the spouse, or the severity of the patient's condition is alone the cause of variation in outcome. It is possible to integrate these findings with those of other studies on the influence of family variables on the outcom of conditions other than alcoholism. Together these studies suggest a general hypothesis linking a breakdown in the cohesiveness, or mutual rewardingness, of family relationships and unfavourable outcomes following treatment or consultation for psychological disorder.

Adult↗