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Biomedical subjects

I N Bruce

Publications and source records attributed to I N Bruce.

At least 37 records · Page 2Linked to original sources
PubMed2000

Factors associated with refractory renal disease in patients with systemic lupus erythematosus: the role of patient nonadherence.

OBJECTIVE: To assess the prevalence and underlying reasons for the development of chronic renal insufficiency (CRI) in patients with systemic lupus erythematosus (SLE) seen over a 3-year period in our lupus clinic, in particular to determine the frequency and types of patient-dependent factors that were associated with nonadherence when it occurred. METHODS: We determined the frequency and types of patient-dependent factors that were associated with the development of CRI in patients with SLE. CRI was defined as a serum creatinine level > or = 200 mumol/l for at least 6 months. RESULTS: Of the 462 patients followed at the lupus clinic between 1995 and 1998, 17 patients developed CRI. Patient-related factors were deemed to be the major reason for the development of CRI in 5 of these. Three of the 5 patients were nonwhite, and the 2 patients who were white were new immigrants. All 5 patients were reluctant to take high-dose corticosteroids because of potential adverse effects. Financial problems contributed to nonadherence in 2 cases. Two patients refused to continue steroids and immunosuppressive therapy and chose to use "alternative" medications as their sole therapy. Of these 5 patients, 3 are now on long-term renal replacement therapy, 1 has died, and 1 patient continues to be followed with a serum creatinine level of 250 mumol/l. CONCLUSION: There is a need for an educational program based on patients' cultural background in order to enhance patients' understanding of the aims, risks, and benefits of therapy in SLE.

Anti-Inflammatory Agents↗
PubMed1999

A case-control study of candidate vasoactive mediator genes in primary Raynaud's phenomenon.

OBJECTIVES: To elucidate possible genetic factors involved in the pathogenesis of primary Raynaud's phenomenon (RP) and to determine the demographic features. METHODS: The allele frequencies of known polymorphisms in four vasoactive candidate genes, eNOS, BKRG, ET-1 and the ETA receptor genes, were compared in a phenotypically homogeneous group of patients with primary RP and a normal control population. RESULTS: In patients with primary RP, there was a higher reporting of both a family history of RP than in controls (45.3% vs 3.1%; P<0.0001) and a personal history of migraine (32.6% vs 7.2%; P<0.0001). No significant differences in allele frequencies of the candidate genes were found. CONCLUSIONS: These findings support the concept that genetic susceptibility exists in primary RP. The high prevalence of migraine suggests that primary RP is part of a more widespread disorder of vascular tone. These findings do not suggest that common molecular variants of these candidate genes are involved in primary RP.

Adult↗
PubMed1999

Factors associated with fatigue in patients with systemic lupus erythematosus.

OBJECTIVE: To examine the relation between fatigue, disease activity, damage, and quality of life measures in patients with systemic lupus erythematosus (SLE). METHODS: Consecutive patients attending the University of Toronto Lupus Clinic were studied. Disease activity was assessed using the SLEDAI and SLAM-R and damage using the SLICC/ACR Damage index. Fatigue was measured by the Fatigue Severity Score (FSS) and health status by the SF-36 questionnaire. In all cases a tender point count was also performed. RESULTS: 81 patients were studied. Their mean (SD) age and disease duration were 43 (12.5) years and 12.7 (8.0) years respectively. The FSS did not correlate with the SLEDAI nor with the SLAM-R. There was no correlation with the SLICC damage index. Fatigue severity correlated with the tender point count (SCC r=0.46, p<0.001), and negatively with all domains of the SF36 (r values -0.50 to -0.82). Disease activity and damage accounted for only 4.8% and 4% respectively of the variance in fatigue severity reported by patients. CONCLUSION: In an outpatient population of SLE patients, fatigue severity correlates with poor health status and a higher tender point count. In patients with SLE, factors associated with quality of life and fibromyalgia seem to have a greater influence on the severity of reported fatigue than does the level of current disease activity.

Adult↗
PubMed1999

Extrarenal disease activity in systemic lupus erythematosus is not suppressed by chronic renal insufficiency or renal replacement therapy.

OBJECTIVE: To assess whether chronic renal impairment (CRI) and/or renal replacement therapy (RRT) in systemic lupus erythematosus (SLE) are associated with reduced extrarenal SLE activity. METHODS: This was a retrospective cohort analysis of patients with SLE who are followed at the University of Toronto Lupus Clinic. Patients with SLE were studied in 2 stages; chronic renal insufficiency (defined as a serum creatinine > 200 mumol/1 for > 6 months) and following the institution of dialysis therapy. Controls consisted of the next 2 age and sex matched patients in the clinic with a history of lupus nephritis who had not developed renal insufficiency. We assessed the flare rate (an increase in nonrenal SLEDAI > or = 1.0) for patients and controls in the first 12 months of followup at the clinic in each stage. RESULTS: Twenty-one patients, 17 female and 4 male, were followed through 25 episodes of CRI or RRT as were 50 controls. In the CRI stage (n = 12), flares occurred in 8 (67%) within one year compared to 14 (58%) of 24 controls (p = NS). In the RRT stage (n = 13), flares occurred in 7 (54%) compared to 16 (62%) of 26 controls (p = NS). The magnitude as well as the characteristics of the flares did not differ between patients and controls in either stage. CONCLUSION: Patients with SLE who develop CRI, or who receive RRT, continue to display evidence of ongoing extrarenal disease activity. Such patients require careful longterm followup for management of their extrarenal disease.

Adult↗
PubMed1999

Natural history of hypercholesterolemia in systemic lupus erythematosus.

OBJECTIVE: To determine the natural history of hypercholesterolemia in the first 3 years of disease in an inception cohort of patients with systemic lupus erythematosus (SLE) followed at a single center and to determine the influence of hypercholesterolemia on the subsequent development of coronary artery disease (CAD) related events. METHODS: We identified patients who were seen at the University of Toronto lupus clinic within 1 year of diagnosis from January 1, 1974, to December 31, 1987, and who were seen at least once a year in the first 3 years. Patients were divided into 3 groups: Normal cholesterol: serum total cholesterol (TC) < 5.2 mmol/l throughout the 3 year period of study. Sustained hypercholesterolemia: at least one measurement of TC of > 5.2 mmol/l in each of the first 3 years at the clinic. Variable hypercholesterolemia: TC > 5.2 mmol/l in no more than 2 of the first 3 years of followup. Patients were followed from inception until the present day. The primary outcome was the time of the first CAD related event (myocardial infarction, angina, or sudden unexplained death). RESULTS: One hundred thirty-four patients (118 women, 16 men) were studied: 33 (24.6%) had normal cholesterol, 54 (40.3%) had sustained hypercholesterolemia, and 47 (35.1%) had variable hypercholesterolemia. Using multiple logistic regression the best predictors of sustained hypercholesterolemia were cumulative dose of steroids, no antimalarial therapy, and age of onset of SLE > 35 years old. CAD related events occurred in 1 (3%) of the normal TC group, 3 (6.4%) of the variable group, and in 15 (27.8%) of the sustained group (p = 0.003), 79% of all CAD events occurred in the sustained group. The best predictors of CAD were sustained hypercholesterolemia, lung involvement, and age at onset of SLE > 35 years. CONCLUSION: Within 3 years of diagnosis, 75.4% of patients with SLE had elevated TC, which was sustained in 40.3% of all patients. Older age at onset as well as increased cumulative dose of steroids and no antimalarial therapy are significant predictors of this group. It is this group that experiences the majority of CAD related events. Aggressive lipid lowering therapy should be targeted at such patients.

Age of Onset↗
PubMed1999

Contribution of traditional risk factors to coronary artery disease in patients with systemic lupus erythematosus.

OBJECTIVE: Several factors have been implicated in the high prevalence of premature coronary artery disease (CAD) in patients with systemic lupus erythematosus (SLE). We hypothesize that variables independent of traditional risk factors contribute significantly to the development of CAD in SLE. We investigated the relative contribution of traditional risk factors in SLE patients with CAD compared to non-SLE patients with premature CAD. METHODS: An age matched retrospective cohort analysis. The prevalence of traditional cardiovascular risk factors (hypertension, hypercholesterolemia, diabetes, smoking, family history) in patients with SLE who developed CAD during the course of their illness was compared to a group of age matched non-SLE subjects with premature CAD. Sexes were analyzed separately using Fisher's exact test and unpaired t tests. RESULTS: Thirty-five patients with SLE (27 women, 8 men) with definite ischemic heart disease were identified along with 397 non-SLE subjects (83 women, 314 men). In women with SLE the mean number of CAD risk factors per cardiac event was 2.0 +/- 0.77 versus 2.90 +/- 1.19 for the comparison group (p = 0.0008). In men with SLE the mean number of CAD risk factors was 1.87 +/- 0.83 versus 2.73 +/- 0.99 in the comparison group (p = 0.016). CONCLUSION: SLE patients with a cardiac event have fewer traditional risk factors than non-SLE patients with premature CAD. Thus premature CAD in SLE cannot be attributed solely to an excess of traditional risk factors.

Adult↗
PubMed1999

The cholesterol lowering effect of antimalarial drugs is enhanced in patients with lupus taking corticosteroid drugs.

OBJECTIVE: To examine the relationship between antimalarial therapy and total cholesterol in patients with systemic lupus erythematosus (SLE) with or without steroid therapy. METHODS: Retrospective study for the University of Toronto Lupus Clinic database between 1976 and 1997. The effects of antimalarials on random total cholesterol levels were assessed in the following situations: patients not receiving steroids (part I) that either initiated or discontinued antimalarials; patients receiving steroids (part II) that were either on a stable dose or initiating antimalarials; and patients initiating steroids with or without antimalarials (part III). Paired t test, Fisher's exact test, and 2 way analysis of variance were used when appropriate. RESULTS: Initiation of antimalarials reduced the baseline total cholesterol by 4.1 % at 3 months in 53 patients (p = 0.020) and by 0.6% at 6 months in 30 patients (p = NS), while the cessation of antimalarials increased the total cholesterol by 3.6% at 3 months in 38 patients (p = NS) and 5.4% at 6 months in 22 patients (p = NS). In 181 patients taking steroids and antimalarials, the mean total cholesterol was 11% less than for 201 patients receiving a comparable dose of steroids alone (p = 0.0023). Initiation of antimalarials on a stable dose of steroids reduced the total cholesterol by 11.3% at 3 months in 29 patients (p = 0.0002) and 9.4% at 6 months in 20 patients (p = 0.004). For patients initiating steroids, the percentage increase in cholesterol was lower in those taking antimalarials compared to patients without antimalarial therapy (p = 0.0149). CONCLUSION: Antimalarials lower total cholesterol in patients receiving steroids and may minimize steroid induced hypercholesterolemia.

Antimalarials↗
PubMed1997

Microscopic polyangiitis. Delineation of a cutaneous-limited variant associated with antimyeloperoxidase autoantibody.

BACKGROUND: Microscopic polyangiitis is a systemic small vessel vasculitis, which, although primarily associated with necrotizing and crescentic glomerulonephritis and pulmonary capillaritis, often has cutaneous and musculoskeletal features. Microscopic polyangiitis is strongly associated with antineutrophil cytoplasmic autoantibodies, most often demonstrating a perinuclear immunostaining pattern. This pattern usually demonstrates specificity for antimyeloperoxidase autoantibodies. We report a case of microscopic polyangiitis, which, even after several years, has remained predominantly cutaneous. OBSERVATIONS: We describe a patient with a 22-year history of cutaneous purpuric vasculitis. The lesions occur in crops at 4- to 6-week intervals and are associated with constitutional upset and elevated serologic inflammatory indexes. The antimyeloperoxidase titers closely correlate with disease activity in this patient. After close, long-term review and extensive investigations, no evidence of necrotizing and crescentic glomerulonephritis, pulmonary capillaritis, or other deep-organ involvement has been detected. CONCLUSIONS: To our knowledge, this is the first report of a long-term evaluation of predominantly cutaneous microscopic polyangiitis and demonstrates that serologically characteristic microscopic polyangiitis may remain limited without subsequent progression to characteristic systemic involvement. This observation contributes to the understanding and characterization of the clinicopathologic spectrum of microscopic polyangiitis.

Adult↗
PubMed1997

Age-related changes in non-receptor dependent generation of reactive oxygen species from phagocytes of healthy adults.

Several authors have shown that neutrophil generation of reactive oxygen species (ROS) declines with advancing age. Similar changes have also been suggested in monocytes. In both cases alterations in second messenger activity have been implicated as the most likely explanation for these observations. The aim of this study was to investigate the effect of age on phagocyte ROS generation, stimulated by the direct activation of protein kinase C (PKC). Venous blood was drawn from normal healthy subjects, cells were separated on a double density gradient into mononuclear and polymorphonuclear (pmn) cells. Phorbol myristate acetate (PMA) was employed as a cell stimulus. Superoxide generation was measured by cytochrome c reduction and myeloperoxidase (MPO) products by measurement of peak luminol chemiluminescence (CL). Fifty-eight subjects, 25 males and 33 females, were studied, median age 49 years (range 26-88 years). Polymorphonuclear cell superoxide generation was significantly higher in males and there was a trend towards higher pmn MPO product generation in males. Using Spearman's ranked correlation coefficient, monocyte superoxide generation was negatively correlated with age (r = -0.473, P < 0.001). No changes in the generation of MPO products was found. There were also trends towards a negative correlation of pmn cytochrome c reduction and peak luminol CL with age in males but not females. Since PMA directly activates protein kinase C, reduced monocyte superoxide generation with increasing age appears to be related to alterations in the ROS generating system downstream of the cell receptor. Impaired monocyte superoxide generation may have implications for non-specific defence against certain infections and early tumour growth in the elderly. Factors underlying these changes in monocyte function therefore require further study.

Adult↗
PubMed1997

A comparison of two nomenclature systems for primary systemic vasculitis.

Recently, two new systems have been proposed for the nomenclature of primary vasculitides: the 1990 American College of Rheumatology (ACR) classification criteria and the 1992 Chapel Hill Consensus Conference (CHCC) definitions. We compared these two systems in the same cohort of patients with primary systemic vasculitis. Twenty-four patients were studied and, applying the 1990 ACR criteria, the diagnoses were Wegener's granulomatosis (WG) (15), Churg Strauss syndrome (CSS) (4), polyarteritis nodosa (PAN) (2) and unclassified (3). Using the CHCC definitions, the diagnoses were WG (5), microscopic polyangiitis (MPA) (8), possible MPA (1), PAN (1) and undefined (9). There was concordance in only five patients (all WG). Significant discordance exists between these two criteria sets. Since the ACR criteria set does not include MPA, WG tends to be overdiagnosed. The Chapel Hill definitions are biopsy dependent and surrogate features for the defining histology are required to allow their practical application.

Adult↗
PubMed1997

Enhanced endothelium-dependent vasodilator responses in patients with systemic vasculitis.

The aim of the study was to investigate endothelium-dependent vasodilator responses in the forearm vasculature of patients with systemic vasculitis. We studied 10 patients with systemic vasculitis and 16 healthy control subjects using forearm venous occlusion plethysmography to assess changes in forearm blood flow in response to acetylcholine (ACh). NG-monomethyl-L-arginine (L-NMMA), was also used to assess the contribution of endothelium derived relaxing factor/nitric oxide (EDRF/NO) to the vasodilator responses to acetylcholine. A significantly greater vasodilator response to ACh was seen in the patient group at all doses infused (p < 0.01). After pre-infusion of L-NMMA, the differences in ACh dilator responses were no longer significant. There was a greater magnitude of inhibition of ACh responses by L-NMMA in the patient group. The enhanced vasodilator response to ACh observed was in part abolished by L-NMMA, suggesting that EDRF/NO is produced in excess in systemic vasculitis. The precise role played by EDRF/NO in the pathogenesis of systemic vasculitis requires further study.

Acetylcholine↗
PubMed1996

Dermatological presentation of disease associated with antineutrophil cytoplasmic antibodies: a report of two contrasting cases and a review of the literature.

Antineutrophil cytoplasmic antibody (ANCA)-associated disease (AAD) constitutes a pathological disease spectrum of a necrotizing vasculitis of small- and medium-sized vessels, extravascular granuloma formation, and necrotizing and crescentic glomerulonephritis, and also a clinical disease continuum which ranges from renal-limited disease to a widespread systemic vasculitis, including Wegener's granulomatosis and microscopic polyangiitis. In the latter, circulating ANCA are an aid to diagnosis and also may play a pathogenic part. Two contrasting patients with AAD are described, both of whom presented primary with dermatological features. These included a cutaneous purpuric vasculitis, orogenital ulceration, infarction of the fingertip, and pyoderma gangrenosum-like ulceration. These cases will familiarize dermatologists with both the concept and dermatological features of AAD.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1995

Chronic suppurative lung disease with associated vasculitis.

We report a patient with chronic bronchiectasis who developed systemic vasculitis. The patient was initially treated with immunosuppression; however, the addition of antibiotic therapy improved control of her vasculitis and the need for immunosuppression was reduced. Chronic bronchial suppuration may have an aetiological role in the pathogenesis of this condition.

Bronchiectasis↗