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I Bruce

Publications and source records attributed to I Bruce.

33 records · Page 2Linked to original sources
PubMed1998

Hypothalamic-pituitary-adrenal axis dysfunction in Alzheimer's disease: lack of association between longitudinal and cross-sectional findings.

OBJECTIVE: The authors examined longitudinal hypothalamic-pituitary-adrenal (HPA) axis function in Alzheimer's disease. METHOD: Cortisol levels of 30 patients with Alzheimer's disease and 17 healthy elderly subjects were measured before and after administration of dexamethasone. These measures were repeated at 9-month intervals in the patients with Alzheimer's disease. RESULTS: At baseline, cortisol levels were higher in the Alzheimer's disease group before and after dexamethasone administration. Although only two of the four patients whose cortisol levels were not suppressed by dexamethasone also had high cortisol levels before dexamethasone administration, basal and postdexamethasone cortisol levels were correlated. HPA axis dysfunction correlated with severity of dementia at baseline but was not stable longitudinally and did not increase with follow-up. CONCLUSIONS: There was no association between longitudinal and cross-sectional findings. The longitudinal data were not consistent with a role for the glucocorticoid cascade hypothesis (that hippocampal cell loss in Alzheimer's disease results in hypercortisolism, which in turn acts as a co-factor in further degeneration) in the pathophysiology of mild and moderate Alzheimer's disease.

Aged↗
PubMed1997

Mental disorders among the community-dwelling elderly in Dublin.

BACKGROUND: The prevalence of mental disorders among the community-dwelling elderly in the catchment area of a psychiatry for the elderly service in Dublin was determined. METHOD: A sample of 1232 individuals aged 65 years and over, identified from general practitioner practice lists, was interviewed using the Geriatric Mental State-AGECAT package. RESULTS: Depression and organic disorder occurred with prevalences of 10.3 and 4.1%, respectively. Depression diagnostic cases had comorbid anxiety at case level in 17.3% and at sub-case level in a further 59.9%. Organic diagnostic cases had comorbid depressive or anxiety symptoms, at case or sub-case level, in 32%. CONCLUSIONS: Depression is the most common mental disorder among the elderly in Dublin. The frequency of anxiety symptoms in the presentation of depression may be a factor in the under-diagnosis or misdiagnosis of depression in the community-dwelling elderly. Comorbid anxiety and depression in organic disorder may represent treatable symptoms.

Aged↗
PubMed1997

Enhanced monocyte generation of reactive oxygen species in primary systemic vasculitis.

OBJECTIVE: Little is known about the role of mononuclear phagocytes in systemic vasculitis. We examined the hypothesis that monocytes from patients with primary systemic vasculitis have increased capacity to generate reactive oxygen species. METHODS: We studied patients with primary systemic vasculitis (n = 24) and compared them with patients with autoimmune related vasculitis (20), peripheral vascular disease (12), and postrenal transplantation (8). Healthy controls were also studied (56). Peripheral blood monocytes were stimulated using phorbol myristate acetate (PMA). We measured the generation of superoxide by cytochrome c reduction and myeloperoxidase (MPO) dependent products using peak luminol chemiluminescence. RESULTS: Patients with primary systemic vasculitis generated significantly more superoxide than all 3 non-vasculitis groups. Superoxide generation in the autoimmune vasculitis group was also higher than other groups but failed to reach significance versus controls (p = 0.07). Generation of MPO dependent products was also significantly higher in patients with primary vasculitis compared to all other groups. Subgroup analysis within the primary vasculitis group showed no correlation of these findings with disease activity, antineutrophil cytoplasmic antibodies, or American College of Rheumatology classification. CONCLUSION: Mononuclear phagocytes act as a source of reactive oxygen species in primary systemic vasculitis. Further study is required to determine if the reactive oxygen species generated act as a mechanism to promote vessel wall injury, or healing in this condition.

Adult↗
PubMed1995

In situ hybridization detection of short viral amplicon sequences within cultured cells and body fluids after the in situ polymerase chain reaction.

Using single primer pairs, intracellular gene sequences of cytomegalovirus (CMV-Towne's strain) and alpha-tubulin were amplified (in situ PCR) from cells in human body fluids and in suspensions. Visualization of CMV amplificants was carried out by in situ hybridization (ISH), using both a biotinylated double-stranded DNA probe and a radiolabelled oligonucleotide probe. Visualization of alpha-tubulin amplificants was achieved using both radiolabelled single-stranded cRNA and oligonucleotide probes. Liberated amplificants were also identified by bands of expected size by gel electrophoresis. The specificity of the PCR products was confirmed by Southern blot analysis. Intracellular amplification was identified both in unfixed cells and, optimally, after brief alcohol fixation, whilst maintaining relative isotonicity in all working solutions. For CMV, enhanced signal was observed in cells (cultured fibroblasts or urine sediment) undergoing in situ PCR using either biotinylated or radiolabelled probes compared with controls undergoing ISH alone. For alpha-tubulin, radiolabelled riboprobes and oligoprobes only produced signals within cells (human peripheral lymphocytes, ascitic fluid and bladder washings from routine cytological specimens) after in situ PCR, but not after ISH alone. Morphological evaluation was superior with biotinylated probes, and minimal back-diffusion effect was found compared with radiolabelled probes. Up to 80% of cells survived thermal cycling. In situ PCR detected short sequence (100 bp) foreign DNA and low copy number genomic DNA, and was superior to ISH alone. In contrast to radiolabelled probes, very small CMV amplificants could be detected without a significant 'back-diffusion' effect when using the large biotinylated probe in this model system.

Animals↗
PubMed1994

The effect of probucol and vitamin E treatment on the oxidation of low-density lipoprotein and forearm vascular responses in humans.

This study investigates the hypothesis that lipid soluble antioxidants may increase the resistance of low-density lipoprotein (LDL) to oxidation and also enhance vascular endothelial responses in humans. In a double-blind parallel group study, 24 hypercholesterolaemic patients already on treatment with simvastatin (20 mg day-1), were randomized to supplementary treatment with probucol (500 mg bd), vitamin E (400 IU daily) or placebo for 8 weeks. Mean serum cholesterol before antioxidant treatment was 7.00 mmol l-1. Resistance of LDL to oxidation by copper was increased by 830% in the probucol group and by 30% in the vitamin E group. However, thiobarbituric acid reacting substances in whole serum were not altered by either antioxidant. Probucol lowered HDL- and LDL-cholesterol levels and increased the QT interval. Forearm vascular responses, as measured by venous occlusion plethysmography, to acetylcholine, glyceryl trinitrate and NG-monomethyl-L-arginine, were not significantly changed by antioxidant treatment. Probucol has a major, and vitamin E a minor, effect on LDL resistance to oxidation but neither compound appears to alter forearm vascular responses in vivo.

Adult↗
PubMed1994

Differential diagnosis of dementia: a prospective evaluation of the DAT Inventory.

OBJECTIVE: To compare prospectively the concordance between the diagnosis of dementia based on clinical criteria and using the DAT Inventory. DESIGN, SETTING, AND PARTICIPANTS: A prospective study of 81 consecutive patients referred to a Memory Clinic. Only patients for whom a definitive diagnosis of dementia was established after 8 to 20 months follow-up were retained in the study (n = 76). MEASUREMENTS: The sensitivity, specificity, positive and negative predictive values, and overall diagnostic accuracy of the DAT Inventory were calculated. Kappa values were also computed. RESULTS: Based on all patients (n = 76), sensitivity and specificity were 71% and 95%, respectively, with 98% positive prediction, 56% negative prediction, 78% overall accuracy, and kappa of 0.54. Of 21 cases not meeting NINCDS/ADRDA criteria for DAT, one patient with multi-infarct dementia was misclassified as DAT on the DAT Inventory. Of 55 DAT cases (NINCDS/ADRDA criteria), 16 patients, predominantly very mild or mixed cases, were classified as non-DAT on the DAT Inventory. When mixed, very mild, and borderline cases were excluded (remaining n = 54), DAT Inventory sensitivity increased to 94%, and specificity remained unchanged at 95%, with 97% positive and 91% negative prediction, 94% overall accuracy, and kappa of 0.88. CONCLUSIONS: In general, scores above the designated cutoff point (> 14/20) on the DAT Inventory are consistent with a clinical diagnosis of DAT (NINCDS/ADRDA criteria). Concordance is best in cases of mild to moderate dementia (Clinical Dementia Rating 1-2). The Inventory is less discriminating as a differential diagnostic instrument in cases of very mild dementia, atypical presentations of DAT, or in cases of mixed pathology.

Aged↗
PubMed1993

Renal replacement therapy in multiple myeloma and systemic amyloidosis.

Renal failure frequently complicates both multiple myeloma and systemic amyloidosis. Renal replacement therapy (RRT) may be poorly tolerated and its role in such patients is not clearly defined. Of fifty patients (26 males and 24 females) referred to a single centre because of renal failure associated with multiple myeloma or systemic amyloidosis 37 progressed to end-stage renal failure and 30 of these patients received RRT. Nine patients have been treated by CAPD, 13 by haemodialysis, and 8 patients have required both forms of dialysis. Overall one year and two year survival rates were 66% and 57% respectively. The median duration on RRT was 7.5 months (range 1-96 months) with a 51% one year, and a 46% two year survival rate. Of 7 patients with amyloidosis who underwent renal transplantation, 3 died within 6 months of transplantation. Undiagnosed cardiac involvement contributed to this early mortality. We conclude that renal replacement therapy is appropriate for some patients with multiple myeloma and systemic amyloidosis who develop endstage renal failure. Careful assessment and selection of patients is necessary prior to renal transplantation.

Adolescent↗
PubMed1992

Comparative metabolism of clinically important precursors of N-desmethyldiazepam using phenobarbitone-pretreated rat liver microsomes.

Phenobarbitone-pretreated male Sprague-Dawley rat liver microsomes were used to examine C3-hydroxylation and N-dealkylation of four clinically important benzodiazepines: diazepam (DZP), prazepam (PZP), pinazepam (PIN) and halazepam (HZP). These substrates differ only in the nature of the N-substituent of the B ring and N-desmethyldiazepam (DMD) is the N-dealkylation product in each case. C3-Hydroxylation was accordingly also studied with DMD as substrate. All monooxygenations were studied with substrates at a concentration of 10 microM, in the absence of solubilizing agents, and under conditions where the production of secondary metabolites was minimized. A 20-fold variation in the rate of C3-hydroxylation was recorded across the five substrates with HZP showing the highest rate and DMD showing the lowest rate. An almost equally large range of variation was shown for the N-dealkylation reaction, with PZP undergoing this biotransformation more than 17 times faster than DZP. Log P values (a measure of lipophilicity) for the five substrates were determined using an HPLC method and a remarkable lack of correspondence between this substrate parameter and either of the monooxygenations was noted. This suggests that multiple substrate determinants govern the relative rates of these monooxygenations. It was, however, notable that the additive rate of metabolism of these substrates by both monooxygenase routes did show an excellent correlation with substrate lipophilicity.

Animals↗
PubMed1991

Glucose analogue inhibitors of glycogen phosphorylase: the design of potential drugs for diabetes.

The T-state crystal structure of the glucose-phosphorylase b complex has been used as a model for the design of glucose analogue inhibitors that may be effective in the regulation of blood glucose levels. Modeling studies indicated room for additional atoms attached at the C1-beta position of glucose and some scope for additional atoms at the C1-alpha position. Kinetic parameters were determined for alpha-D-glucose: Ki = 1.7 mM, Hill coefficient n = 1.5, and alpha (synergism with caffeine) = 0.2. For beta-D-glucose, Ki = 7.4 mM, n = 1.5, and alpha = 0.4. More than 20 glucose analogues have been synthesized and tested in kinetic experiments. Most were less effective inhibitors than glucose itself and the best inhibitor was alpha-hydroxymethyl-1-deoxy-D-glucose (Ki = 1.5 mM, n = 1.3, alpha = 0.4). The binding of 14 glucose analogues to glycogen phosphorylase b in the crystal has been studied at 2.4-A resolution and the structure have been refined to crystallographic R values of less than 0.20. The kinetic and crystallographic studies have been combined to provide rationalizations for the apparent affinities of glucose and the analogues. The results show the discrimination against beta-D-glucose in favor of alpha-D-glucose is achieved by an additional hydrogen bond made in the alpha-glucose complex through water to a protein group and an unfavorable environment for a polar group in the beta pocket. The compound alpha-hydroxymethyl-1-deoxy-D-glucose has an affinity similar to that of glucose and makes a direct hydrogen bond to a protein group. Comparison of analogues with substituent atoms that have flexible geometry (e.g., 1-hydroxyethyl beta-D-glucoside) with those whose substituent atoms are more rigid (e.g., beta-azidomethyl-1-deoxyglucose or beta-cyanomethyl-1-deoxyglucose) indicates that although all three compounds make similar polar interactions with the enzyme, those with more rigid substituent groups are better inhibitors. In another example, alpha-azidomethyl-1-deoxyglucose was a poor inhibitor. In the crystal structure the compound made several favorable interactions with the enzyme but bound in an unfavorable conformation, thus providing an explanation for its poor inhibition. Attempts to utilize a contact to a buried aspartate group were partially successful for a number of compounds (beta-aminoethyl, beta-mesylate, and beta-azidomethyl analogues). The beta pocket was shown to bind gentiobiose (6-O-beta-D-glucopyranosyl-D-glucose), indicating scope for binding of larger side groups for future studies.

Deoxyglucose↗
PubMed1991

Towards time-resolved diffraction studies with glycogen phosphorylase.

Laue diffraction with high intensity, broad-spectrum synchrotron radiation sources allows three-dimensional data sets on protein crystals to be recorded in seconds or milliseconds and opens the way for time-resolved studies on dynamic events in crystals. This chapter briefly reviews the field and describes progress towards time-resolved studies with glycogen phosphorylase. Methods for the synchronization of the start of reaction with the start of data collection have been developed for the phosphorolytic reaction of glycogen phosphorylase. The compound 3,5-dinitrophenylphosphate is photolabile, yielding Pi and the by-product, 3,5-dinitrophenol, which is non-reactive with the enzyme. Spectroscopic studies show that the compound has good quantum yield and that photolysis is rapid (greater than 1000 s-1). Release of the dinitrophenylate anion, following a pulse of light from a xenon flash lamp, has been monitored with a diode array spectrophotometer specially adapted for measurements on crystals. In a laboratory X-ray experiment with crystals of glycogen phosphorylase b, release of Pi and formation of the enzyme-product complex have been demonstrated. The way is now open for Laue diffraction studies on the catalytic reaction in the crystal.

Crystallography↗
PubMed1984

Potentiation by purines of the growth-inhibitory effects of sulphonamides on Escherichia coli K12 and the location of the gene which mediates this effect.

The increased toxicity of sulphonamides for Escherichia coli in the presence of low concentrations (50-100 microM) of purines or purine nucleosides has been confirmed and investigated further. The potentiating effect of a purine was dependent upon the activity of the appropriate phosphoribosyl transferase: a gpt mutant strain was not potentiated by guanine but remained fully sensitive to the addition of adenine. Mutants resistant to the potentiating effect of all purines have been isolated and partially characterized. The site of these mutations has been located in the region between oriC and asnA at minute 83 on the E. coli chromosome map. It is suggested that this locus be temporarily designated psp (potentiation of sulphonamides by purines) because these mutants have unaltered sensitivities to sulphonamides acting alone. Mutations in PurA, purR and folB did not affect the potentiation of sulphonamides by purines. Hypoxanthine-insensitive strains harbouring lambda asn20 were as sensitive as the wild-type to the potentiating effect. This result suggests that these lysogens are heterozygous for psp and that the wild-type allele is dominant. It is probable that psp is a regulatory gene, affecting some rate-limiting step in the biosynthesis of methionine.

Chromosome Mapping↗
PubMed1981

The Volunteer Centre.

Explore the source record for details and available documents.

Community Health Centers↗
PubMedDate not supplied

A memory clinic for the assessment of mild dementia.

The aims and experience of work in a specialist memory clinic' are described with reference to the first 200 patients attending the service. 93.5% of attenders were found to suffer from dementia. 67.9% of these fulfilled criteria for probable/possible Alzheimer's disease or other primary degenerative dementias and 8.6% fulfilled criteria for vascular dementia. In the remaining cases the aetiology of the dementia was considered to be multifactorial. The memory clinic proved to be an important resource for demented patients, their carers, and for research projects.

Aged↗