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Biomedical subjects

I Bruce

Publications and source records attributed to I Bruce.

At least 19 recordsLinked to original sources
PubMed2000

Atherosclerosis and systemic lupus erythematosus.

The description of late-stage mortality and morbidity has been an important contribution to the understanding of systemic lupus erythematosus (SLE) in the past decade. Among the major factors in this clinical spectrum of SLE is the development of accelerated atherosclerosis. This condition has been recognized clinically with the documentation of myocardial infarction and angina in young women with SLE. This accelerated atherosclerosis has also been recognized at postmortem examinations. The exact mechanism for accelerated atherosclerosis remains unclear. However, disease activity with its immunologic events, the anticardiolipin syndrome, and the effect of corticosteroids in promoting hyperlipidemia contribute to its development. It appears that SLE may be a risk factor, in addition to the usual risk factors for the development of atherosclerosis. It has recently been shown that antimalarials may prevent some of the hyperlipidemia caused by corticosteroids. As evidence for the presence of subclinical atherosclerosis in these patients is accumulating, earlier diagnosis and treatment of events may be possible, and preventive measures may be instituted earlier.

Adrenal Cortex Hormones↗
PubMed2000

Do the eyes have it? Cues to the direction of social attention.

The face communicates an impressive amount of visual information. We use it to identify its owner, how they are feeling and to help us understand what they are saying. Models of face processing have considered how we extract such meaning from the face but have ignored another important signal - eye gaze. In this article we begin by reviewing evidence from recent neurophysiological studies that suggests that the eyes constitute a special stimulus in at least two senses. First, the structure of the eyes is such that it provides us with a particularly powerful signal to the direction of another person's gaze, and second, we may have evolved neural mechanisms devoted to gaze processing. As a result, gaze direction is analysed rapidly and automatically, and is able to trigger reflexive shifts of an observer's visual attention. However, understanding where another individual is directing their attention involves more than simply analysing their gaze direction. We go on to describe research with adult participants, children and non-human primates that suggests that other cues such as head orientation and pointing gestures make significant contributions to the computation of another's direction of attention.

Journal Article↗
PubMed2000

Three-year prognosis of depression in the community-dwelling elderly.

BACKGROUND: Depression is the most common mental disorder in the community-dwelling elderly. AIMS: To determine the three-year prognosis of depression in a cohort of 127 community-dwelling elderly subjects and identify factors relevant to outcome. METHOD: The subjects, diagnosed depressed at year 0 using the GMS-AGECAT package, were followed up three years later. A number of factors were investigated for an association with recovery from, or persistence of, depression. RESULTS: At follow-up, 30.2% of the depressed subjects had died, 34.9% had persistent or relapsed case-level depression, 24.5% had other case- or sub-case-level mental illness and 10.4% had recovered completely. Physical ill-health, bereavement and positive family history of depression were associated with poor outcome, whereas treatment with antidepressant medication significantly improved prognosis. CONCLUSIONS: Late-life depression in community-dwelling subjects is a chronic condition. However, the positive response to antidepressant medication suggests that it should be vigorously treated.

Aged↗
PubMed1999

Dysthymia among the community-dwelling elderly.

There are few data on the clinical features of dysthymia among the community-dwelling elderly. Forty elderly individuals with dysthymic disorder were identified following screening in the community with GMS-AGECAT. A detailed clinical history was obtained and DSM-IV checklists and standardized scales were used, at a second interview. Comparisons were made with a group of 630 non-depressed elderly from the same community. Dysthymia was predominately of late onset (93%) and associated with a major stressor in 65% of cases. Comorbid axis 1 disorders were present in 15% of dysthymics and an axis 2 disorder in 10%. The dysthymic group had significantly higher degrees of physical impairment than the non-depressed elderly. The symptom profile demonstrated prominent anxiety and functional features. Eighty-three per cent of the elderly with dysthymia had presented to their GP with anxiety/depressive symptoms at some stage during the dysthymic disorder. The presentation of dysthymia in older people differs from that in earlier life. Late life dysthymia is less associated with axes 1 and 2 comorbidity but is associated with significant degrees of physical impairment. Dysthymia in older people presents to primary care, rather than specialist services, and interventions must be delivered at this level.

Age of Onset↗
PubMed1999

Benzodiazepine use among the elderly in the community.

Benzodiazepines are the most commonly prescribed psychotropic drug in the elderly. Benzodiazepines with a long duration of action can produce marked sedation and psychomotor impairment in older people, and are associated with an increased risk of hip fracture and of motor vehicle crash. One thousand seven hundred and one individuals of 65 years and over, identified from General Practitioner lists, were interviewed using the Geriatric Mental State-AGECAT package and current psychotropic drug use was recorded. Benzodiazepines were classified as having a short or long elimination half-life. Two hundred and ninety-five (17.3%) individuals were taking a benzodiazepine, with use in females being twice that in males. Of the 295, 152 (51.5%) were taking a long acting benzodiazepine and the use of long acting anxiolytic type benzodiazepines was particularly common. Fifty-two (17.6%) benzodiazepine users were taking one or more other psychotropic drugs. A benzodiazepine was used by eight of 18 (44.4%) subjects with an anxiety disorder, 62 of 180 (34.4%) individuals with depression, and seven of 71 (9.9%) people with dementia. Four-fifths of older people on a psychotropic drug were taking a benzodiazepine, highlighting the importance of this class of drug in the elderly population. The choice of a benzodiazepine with a long duration of action, which have been shown to be associated with serious adverse events in the elderly in over one half of benzodiazepine users, is of concern. The potential for adverse effects was further accentuated by polypharmacy practices. The choice of benzodiazepine for an older person has important consequences and should be addressed in greater detail with primary care.

Aged↗
PubMed1998

Psychiatric morbidity in cohabitants of community-dwelling elderly depressives.

OBJECTIVE: To determine the effect of living with a depressed elderly individual on the mental health of the cohabitant carer. METHOD: Case-control study comparing rates of psychiatric morbidity in cohabitants of depressed versus well elderly. SETTING: Community sample. PARTICIPANTS: 44 couples, one partner with AGECAT depression, and 44 couples, one partner diagnosed well by AGECAT. Cohabitants were matched for gender, age and physical health status. All subjects were aged 65 years and over. MAIN OUTCOME MEASURE: Odds ratio of case or subcase depression and/or neurotic disorder in cohabitants of depressed elderly. RESULTS: 28/44 (64%) cohabitants of depressed subjects were cases (N = 9) or subcases (N = 19) of depression, neurotic disorder or both, compared to 13/44 (29%) cases (N = 1) or subcases (N = 12) in cohabitants of well subjects (OR = 6.33, 95% CI (1.7-18.3), p = < 0.001). CONCLUSION: This study reveals high levels of psychiatric morbidity, primarily depression and anxiety symptoms, in the cohabitants of depressed community-dwelling elderly. This suggest that living with a depressed elderly person may have an adverse effect on the mental health of the cohabitant. Increased recognition of the potential psychiatric morbidity in this group is needed.

Aged↗
PubMed1998

A sensitive and robust method for measles RNA detection.

The aim of this study was to compare measles RNA amplification methods and to develop and select the most rapid, sensitive and robust procedure. The use of hybrid capture for measles RNA isolation was evaluated, and three RNA amplification detection techniques were compared. These were: (a) reverse transcription followed by nested polymerase chain reaction (RT-PCR) with MMLV reverse transcriptase and Taq polymerase; (b) a combined RT-PCR reaction using rTth polymerase; and (c) NASBA. An internal positive control was also developed. The sensitivities of the detection methods were quantified by using a dilution series of a known amount of total RNA from measles-infected Vero cells or by calculation of the number of transcript molecules (produced from a recombinant plasmid containing an insert measles nucleoprotein DNA) present in each amplification reaction, respectively. The results indicated that hybrid capture followed by combined RT-PCR with rTth polymerase was the most reproducibly robust and sensitive protocol and could detect as few as 10(4) synthetic measles RNA transcripts added to tissue homogenates. However, NASBA proved to be the most sensitive method for measles RNA detection in water.

Animals↗
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↗