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Biomedical subjects

P Sims

Publications and source records attributed to P Sims.

At least 37 records · Page 2Linked to original sources

Aetiological considerations and risk factors for multi-infarct dementia.

One hundred and seventy five multi-infarct dementia (MID) patients were evaluated for risk factors for stroke as well as for the types of cerebrovascular lesions that were present. The incidence of associated risk factors for stroke were as follows: hypertension (66%), heart disease (47%), cigarette smoking (37%), diabetes mellitus (20%), moderate alcohol consumption (19%) and hyperlipidaemia (21%). The most frequently occurring type of lesions were multiple lacunar infarctions of the brain (43%). These were combined with other types of stroke in an additional 21%. Atherosclerotic occlusive disease of the carotid and vertebrobasilar arteries occurred alone in 18% and was associated with other types of stroke in another 25%. Embolic cerebral infarctions were present alone in 8% and were combined with other types of stroke in 15%. MID was more frequent in men (62%) than women (p less than 0.002). Mean bihemispheric gray matter cerebral blood flow (CBF) values showed a fluctuating course and when results were pooled and compared between different types of MID, extracranial occlusive disease and/or multiple lacunar infarctions resulted in lowest CBF values. The location of cerebral infarctions was more importantly related to cognitive impairments than was the total volume of infarcted brain. Mortality rates among 125 MID patients followed for 31 months has been 5%. Correct clinical classification of the types of cerebrovascular lesions was confirmed in three necropsied cases.

Aged

Cognition and cerebral blood flow fluctuate together in multi-infarct dementia.

Longitudinal measurements of cognitive ability measured by serial testing using the Cognitive Capacity Screening Examination (CCSE) were correlated with cerebral blood flow (CBF) throughout (mean +/- SD) 19.9 +/- 12.6 months among 57 patients with multi-infarct dementia, 17 with dementia of the Alzheimer's type, 10 with both, and among 32 age-matched elderly normal controls. Longitudinal CCSE and CBF measurements among controls yielded stable normative values. Reduced mean CCSE scores correlated directly with CBF reductions in patients with multi-infarct dementia (p less than 0.0005) and dementia of the Alzheimer's type (p less than 0.028). Patients with multi-infarct dementia had CCSE scores with retest variability exceeding those of controls (p less than 0.001) and of patients with dementia of the Alzheimer's type (p less than 0.003). CCSE scores and CBF changed together 78.6% (p less than 0.001) of the time in patients with multi-infarct dementia compared with 66.2% of the time (p less than 0.01) in those with both, 62.9% of the time (p less than 0.05) in those with dementia of the Alzheimer's type, and 47.7% of the time (NS) in controls. Further analyses indicated that changes in CCSE scores and CBF were predominantly progressive declines in patients with dementia of the Alzheimer's type, whereas the changes were more bidirectional (both increases and decreases) in patients with multi-infarct dementia; these differences were also significant. Results support the diagnostic usefulness of the Hachinski ischemic scale and confirm that both cognition and CBF fluctuate together among patients with multi-infarct dementia, whereas patients with dementia of the Alzheimer's type exhibit a more stable course, with progressive declines in cognition and CBF.

Aged

Operation of a support service team in the emergency department of a general hospital.

We describe the development and operation of an emergency support service team in the Emergency Department of the Kingston General Hospital, Kingston, Ont. The team, composed of professionals from other departments of the hospital, provides emotional and practical support to family members or survivors in medical emergencies. We discuss the roles of the team members and their procedures for dealing with distress and grief.

Accidents, Traffic

Functional dysphonia in adolescence: two case reports.

Reports of functional dysphonia in children and adolescents under 16 years of age are few. Approximately a dozen cases have been reported in the English literature over the past 35 years. Most of the articles appear in journals related to the fields of speech, hearing and communication with a few in the Otorhinolaryngologic journals. Published papers in psychiatric journals dealing with voice or speech disorders are virtually nonexistent. In children and adolescents the two most common varieties are the Whispering Syndrome, which occurs predominantly in girls, and the Hysterical High Pitched Voice seen mostly in boys. This paper discusses these two varieties of functional dysphonia and presents a case example of each.

Adolescent

The metabolism of 9-methylanthracene by rat-liver microsomal preparations.

The metabolism of 9-methylanthracene by liver microsomal preparations from 3-methylcholanthrene-treated rats was examined. The principal metabolites identified were 9-hydroxymethylanthracene, the 1,2- and 3,4-dihydrodiols of the parent hydrocarbon and the 3,4-dihydrodiol of the 9-hydroxymethyl derivative. A small amount of a product that appeared to be a phenolic derivative of the hydrocarbon was also formed. The structures of the major metabolites were confirmed by u.v., n.m.r., and mass-spectral analysis and, wherever possible, by direct comparison of their chromatographic properties with those of the authentic compounds. 9-Hydroxymethylanthracene was further metabolized by rat-liver microsomal preparations to the 3,4-dihydrodiol but not to the related 1,2-dihydrodiol.

Animals

Metabolic activation of 7,12-dimethylbenz[a]anthracene in rat mammary tissue: fluorescence spectral characteristics of hydrocarbon-DNA adducts.

The hydrocarbon-deoxyribonucleoside adducts present in DNA isolated from the mammary glands of rats that had been treated with 7,12-dimethylbenz[a]anthracene (DMBA) were separated by Sephadex LH20 column chromatography, purified by high performance liquid chromatography (HPLC), and examined by photon-counting spectrophotofluorimetry. The adducts were found to have anthracene-like fluorescence spectra which is consistent with the reaction of diol-epoxides formed in the 1,2,3,4-ring of DMBA with mammary gland DNA.

9,10-Dimethyl-1,2-benzanthracene

The metabolism of 9,10-dimethylanthracene by rat liver microsomal preparations.

The metabolism of the weakly-carcinogenic hydrocarbon, 9,10-dimethylanthracene (DMA) by rat-liver microsomal preparations has been examined. 9-Hydroxymethyl-10-methylanthracene (9-OHMeMA) and 9,10-dihydroxymethyl-anthracene (9,10-DiOHMeA) were identified as metabolites by comparing their chromatographic and spectral properties with those of the authentic compounds. The trans-1,2-dihydro-1,2-dihydroxy derivative of DMA (DMA 1,2-diol) was the major metabolite formed which was identified by its chromatographic, u.v., n.m.r. and mass spectral properties. The dihydrodiol was also formed in the oxidation of DMA in an ascorbic acid-ferrous sulphate-EDTA system. Two other dihydrodiols that were formed from DMA by metabolism appeared to be the trans-1,2- and 3,4-dihydrodiols of 9-OHMeMA (9-OHMeMA 1,2-diol and 9-OHMeMA 3,4-diol) and the further metabolism of DMA 1,2-diol yielded both of these dihydrodiols. When 9-OHMeMA was further metabolized, two main metabolites were formed; one was identified as 9,10-DiOHMeA and the other appeared to be 9-OHMeMA 3,4-diol. No metabolites were detected when 9,10-DiOHMeA was incubated with rat-liver microsomal fractions.

Animals

Metabolic activation of benzo[a]pyrene in human skin maintained in short-term organ culture.

The metabolic activation of benzo[a]pyrene (BP) was examined in six samples of human skin after topical application of the hydrocarbon to the skin in short-term organ culture. The results show that all of the samples were capable of metabolizing BP to water-soluble products and to ether-soluble products that included the 4,5-, 7,8- and 9,10-dihydrodiols and a product which had chromatographic properties identical with those of authentic trans-11,12-dihydro-11,12-dihydroxybenzo[a]pyrene (BP-11,12-diol). The major BP-deoxyribonucleoside adduct detected in each skin sample appeared to be formed from the reaction of r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BP-7,8-diol 9,10-oxide) with deoxyguanosine residues in DNA.

Benzo(a)pyrene

The metabolism of 7,12-dimethylbenz[a]anthracene and 7-hydroxymethyl-12-methylbenz[a]anthracene by rat liver and adrenal homogenates and by rat adrenocortical cells.

The metabolism of 3H-labelled 7,12-dimethylbenz[a]anthracene (DMBA) and of 7-hydroxymethyl-12-methylbenz[a]anthracene (7-OHM-12-MBA) into solvent- and water-soluble and protein-bound derivatives has been examined in rat liver and adrenal homogenates and in rat adrenocortical cells in culture. Although the overall extents of metabolism of the substrates by the two types of homogenate were similar, there was twice as much binding to protein in incubations with the 7-hydroxymethyl derivative. Rat adrenal cells in culture metabolized DMBA more extensively than 7-OHM-12-MBA and converted much more of the parent hydrocarbon into water-soluble derivatives. Both hydrocarbons were metabolized to yield dihydrodiols that were separated and identified by high performance liquid chromatography (HPLC). The 8,9-dihydrodiol was the major dihydrodiol formed from DMBA but, with 7-OHM-12-MBA as substrate, metabolism was diverted to the 10,11- and 3,4-positions in adrenal and hepatic preparations respectively. The viability of rat adrenocortical cells in culture, as measured by trypan blue exclusion, did not appear to be affected by treatment with DMBA, 7-OHM-12-MBA, the sulphate ester of 7-OHM-12-MBA or by 3,4-dihydro-3,4-dihydroxy-7-hydroxymethyl-12-methylbenz[a]anthracene.

9,10-Dimethyl-1,2-benzanthracene

Tumour-initiating activities of dihydrodiols of dibenz[a,c]anthracene.

The tumor-initiating activities of dibenz[a,c]anthracene (DBA) and of the related trans-1,2-, 3,4- and 10,11-dihydrodiols have been examined on mouse skin subsequently promoted with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The 1,2- and 10,11-dihydrodiols were active and were more active than equivalent doses of either the parent hydrocarbon or the 3,4-dihydrodiol. The data are discussed in relation to possible mechanisms that may be involved in the metabolic activation of DBA.

Animals

Formation of the 1,2-diol as a metabolite of 7,12-dimethylbenz[a]-anthracene by rodent and human skin.

Rodent and human skin maintained in short-term organ culture was treated with 3H-labelled 7,12-dimethylbenz[a]-anthracene. Extracts of the rodent tissue and culture fluid in which either mouse, rat or human skin had been maintained were found to contain radioactive material that possessed the chromatographic characteristics of trans-1,2-dihydro-1,2-dihydroxy-7,12-dimethylbenz[a]anthracene when it was examined in two different h.p.l.c. systems. When the metabolite was treated with hot mineral acid, the two radioactive products formed co-chromatographed with the phenols that were formed when the reference dihydrodiol was similarly treated. Acetylation of the isolated metabolite yielded a single product that had chromatographic properties identical to those of the diacetate of the reference dihydrodiol. Taken together these data show that the 1,2-dihydrodiol of 7,12-dimethylbenz[a]anthracene is formed as a metabolite of this hydrocarbon by rodent and human skin maintained in short-term organ culture.

9,10-Dimethyl-1,2-benzanthracene

Preferential binding of polycyclic hydrocarbons to matrix-bound DNA in rat-liver nuclei.

The reactions of benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene metabolites and of r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene with the DNA of matrix-bound and released chromatin fractions of rat-liver nuclei have been examined. Qualitatively there were no differences between the DNA-bound metabolites in each fraction but more binding to matrix-bound DNA occurred. Evidence was obtained that the increased binding of hydrocarbon to matrix-bound DNA was not dependent upon the proximity of hydrocarbon-metabolizing enzymes and Sephadex LH20 chromatography showed that the differences between the fractions were not due to contamination of DNA with residual proteins. The conformation of the matrix-bound chromatin may make its DNA more accessible to reactive metabolites than that of released chromatin.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide

Metabolic activation of chrysene by hamster embryo cells: evidence for the formation of a 'bay-region' diol-epoxide-N2-guanine adduct in RNA.

Ribonucleoside-hydrocarbon adducts present in hydrolysates of RNA isolated from hamster embryo cells treated with 3H-labelled chrysene were examined by chromatography on Sephadex LH20 and by h.p.l.c. on Zorbax ODS. Two adducts formed in cells had chromatographic properties identical to those of two synthetic adducts formed when r-1,t-2-dihydroxy-t-3,4-oxy-1,2,3,4-tetrahydrochrysene (antichrysene 1,2-diol 3,4-oxide) reacted with poly G in vitro. Another adduct formed in cells had chromatographic properties identical to those of a synthetic adduct formed when antichrysene 1,2-diol 3,4-oxide reacted with poly A. In addition to the characterized adducts, other minor adducts were detected whose structures are not known. The structure of the more abundant guanosine--hydrocarbon adduct formed in cells was investigated by determining its pK values and stability in 1 M KOH. The structures of the synthetic guanosine--hydrocarbon adducts were investigated by 1H-n.m.r. spectroscopy. The data show that, in the hydrocarbon--guanosine adducts studied, the hydrocarbon moiety is attached to the exocyclic amino group of guanine.

Animals

Inactivation of a diol-epoxide and a K-region epoxide with high efficiency by glutathione transferase X.

Four glutathione transferases (EC 2.5.1.18), glutathione transferases A, B, and C and a hitherto unknown form, termed X, were purified to apparent homogeneity from rat liver cytosol. They were investigated for their abilities to inactivate two mutagenic epoxides derived from the polycyclic aromatic hydrocarbon benz(a)anthracene, the K-region epoxide benz(a)anthracene 5,6-oxide and the diol-epoxide r-8,t-9-dihydroxy-t-10,11-oxy-8,9,10, 11-tetrahydrobenz(a)anthracene. Mutagenic activity was determined using Salmonella typhimurium his- strain TA100. Glutathione alone had little if any influence on the mutagenicity of the diol-epoxide but significantly decreased the mutagenic effect of the K-region epoxide. This inactivation was enhanced by the addition of glutathione transferases. Both epoxides were inactivated by glutathione in the presence of each of the four enzymes, but with varying efficiencies. Inactivation of the K-region epoxide (in terms of its mutagenicity in the presence of glutathione) required extremely little enzyme, about 1000 times less than for the diol-epoxide. On a molar basis, glutathione transferase X (followed by C greater than A greater than or equal to B) was clearly the most efficient enzyme in inactivating both substrates and also more efficient than were three other purified enzymes (microsomal epoxide hydrolase, cytosolic epoxide hydrolase, and dihydrodiol dehydrogenase) previously investigated in this test system. Taking into account the amounts of enzyme present in rat liver, the glutathione transferases C and X were most effective in inactivating the epoxides examined. Thus, the newly discovered glutathione transferase X appears to be of substantial significance in the inactivation of two structural prototypes of epoxides derived from polycyclic aromatic hydrocarbons, a K-region epoxide and a non-bay-region vicinal diol-epoxide.

Animals