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1.  Breast Cancer in Systemic Lupus Erythematosus 
Oncology  2013;85(2):117-121.
Objective
Evidence points to a decreased breast cancer risk in systemic lupus erythematosus (SLE). We analyzed data from a large multisite SLE cohort, linked to cancer registries.
Methods
Information on age, SLE duration, cancer date, and histology was available. We analyzed information on histological type and performed multivariate logistic regression analyses of histological types according to age, SLE duration, and calendar year.
Results
We studied 180 breast cancers in the SLE cohort. Of the 155 cases with histology information, 11 were referred to simply as ‘carcinoma not otherwise specified’. In the remaining 144 breast cancers, the most common histological type was ductal carcinoma (n = 95; 66%) followed by lobular adenocarcinoma (n = 11; 8%), 15 cancers were of mixed histology, and the remaining ones were special types. In our regression analyses, the independent risk factors for lobular versus ductal carcinoma was age [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.01–1.14] and for the ‘special’ subtypes it was age (OR 1.06, 95% CI 1.01–1.10) and SLE duration (OR 1.05, 95% CI 1.00–1.11).
Conclusions
Generally, up to 80% of breast cancers are ductal carcinomas. Though our results are not definitive, in the breast cancers that occur in SLE, there may be a slight decrease in the ductal histological type. In our analyses, age and SLE duration were independent predictors of histological status.
doi:10.1159/000353138
PMCID: PMC3934367  PMID: 23887245
Breast cancer; Systemic lupus erythematosus; Histopathology; Epidemiology
2.  SF-36 summary and subscale scores are reliable outcomes of neuropsychiatric events in systemic lupus erythematosus 
Annals of the rheumatic diseases  2011;70(6):961-967.
Objective
To examine change in health-related quality of life (HRQoL) in association with clinical outcomes of neuropsychiatric (NP) events in SLE.
Methods
An international study evaluated newly diagnosed SLE patients for NP events attributed to SLE and non-SLE causes. Outcome of events was determined by physician-completed 7-point scale and compared to patient-completed SF-36 questionnaires. Statistical analysis used linear mixed-effects regression models with patient specific random effects.
Results
274 patients (92% female; 68% Caucasian), from a cohort of 1400, had ≥ 1 NP event where the interval between assessments was 12.3 ± 2 months. The overall difference in change between visits in mental component summary (MCS) scores of the SF-36 was significant (p<0.0001) following adjustments for gender, ethnicity, center and previous score. A consistent improvement in NP status (N=295) was associated with an increase in the mean(SD) adjusted MCS score of 3.66(0.89) in SF-36 scores. Between paired visits where NP status consistently deteriorated (N=30), the adjusted MCS score decreased by 4.00(1.96). For the physical component summary (PCS) scores the corresponding changes were +1.73(0.71) and −0.62(1.58) (p<0.05) respectively. Changes in SF-36 subscales were in the same direction (p<0.05; with the exception of role physical). Sensitivity analyses confirmed these findings. Adjustment for age, education, medications, SLE disease activity, organ damage, disease duration, attribution and characteristics of NP events did not substantially alter the results.
Conclusion
Changes in SF-36 summary and subscale scores, in particular those related to mental health, are strongly associated with the clinical outcome of NP events in SLE patients.
doi:10.1136/ard.2010.138792
PMCID: PMC3795436  PMID: 21342917
Systemic lupus erythematosus; Neuropsychiatric; Inception cohort; Health related quality of life; SF-36
3.  Atherosclerotic Vascular Events in a Multinational Inception Cohort of Systemic Lupus Erythematosus (SLE) 
Arthritis care & research  2010;62(6):881-887.
Objective
To describe vascular events during an 8 year follow-up in a multicentre SLE inception cohort and their attribution to atherosclerosis.
Methods
Clinical data including co-morbidities are recorded yearly. Vascular events are recorded and attributed to atherosclerosis or not. All events met standard clinical criteria. Factors associated with atherosclerotic vascular events were analysed using descriptive statistics, t-tests and χ2. Stepwise multivariate logistic regression was used to assess the association of factors with vascular events attributed to atherosclerosis.
Results
Since 2000, 1249 patients have been entered into the cohort. There have been 97 vascular events in 72 patients. These include: myocardial infarction (13), angina (15), congestive heart failure (24), peripheral vascular disease (8), transient ischemic attack (13), stroke (23), pacemaker insertion (1). Fifty of the events were attributed to active lupus, 31events in 22 patients were attributed to atherosclerosis, and 16 to other causes. Time from diagnosis to first atherosclerotic event was 2.0 ± 1.5 years. Compared to patients followed for 2 years without atherosclerosis events (615), at enrolment patients with AVE were more frequently Caucasian, male, older at diagnosis of SLE, obese, smokers, hypertensive and had a family history of coronary artery disease. On multivariate analysis only male gender and older age at diagnosis were associated factors.
Conclusion
In an inception cohort with SLE followed for up to 8 years there were 97 vascular events but only 31 were attributable to atherosclerosis. Patients with atherosclerotic events were more likely to be male and to be older at diagnosis of SLE.
doi:10.1002/acr.20122
PMCID: PMC2989413  PMID: 20535799
4.  Modification of hypertension and hypercholesterolaemia in patients with systemic lupus erythematosus: a quality improvement study 
Annals of the Rheumatic Diseases  2006;65(1):115-117.
Background
Hypercholesterolaemia and hypertension are risk factors for coronary artery disease in patients with systemic lupus erythematosus (SLE).
Objective
To examine the recognition and management of hypercholesterolaemia and hypertension in patients with SLE before and after a quality improvement study.
Method
Patients with SLE have been followed up prospectively at the University of Toronto Lupus Clinic since 1970. The charts of all patients who entered the clinic since 1990 were reviewed to ensure completeness of data on anti‐hypertensive treatment (AHT) and lipid lowering agents (LLA). Recognition and management of hypercholesterolaemia and hypertension were evaluated for the periods 1990–1995 and 1996–2001.
Results
Comparison of treatment between time periods showed that during 1990–1995 204/559 (36%) patients seen were hypertensive, of whom 180 (88%) were receiving AHT, and during 1996–2001 241/576 (42%) patients seen were hypertensive, of whom 232 (96%) were receiving AHT (p = 0.0013). A comparison of treatment for hypercholesterolaemia showed that 21/236 (9%) hypercholesterolaemic patients were being treated with LLA in the earlier period compared with 74/261 (28%) in the later period (p<0.0001).
Conclusions
Treatment for hypertension and hyperlipidaemia has increased in the past 6 years compared with the previous 6 years, but a number of patients eligible for these treatments remain untreated.
doi:10.1136/ard.2005.038802
PMCID: PMC1798000  PMID: 16344496
hypertension; hypercholesterolaemia; systemic lupus erythematosus; quality improvement
5.  Prospective Analysis Of Neuropsychiatric Events In An International Disease Inception Cohort of SLE Patients 
Annals of the rheumatic diseases  2009;69(3):529-535.
Objectives
To determine the frequency, accrual, attribution and outcome of neuropsychiatric (NP) events and impact on quality of life over 3 years in a large inception cohort of SLE patients.
Methods
The study was conducted by the Systemic Lupus International Collaborating Clinics. Patients were enrolled within 15 months of SLE diagnosis. NP events were identified using the ACR case definitions and decision rules were derived to determine the proportion of NP disease attributable to SLE. The outcome of NP events was recorded and patient perceived impact determined by the SF-36.
Results
There were 1206 patients (89.6% female) with a mean (±SD) age of 34.5±13.2 years. The mean disease duration at enrollment was 5.4±4.2 months. Over a mean follow-up of 1.9±1.2 years 486/1206 (40.3%) patients had ≥1 NP events which were attributed to SLE in 13.0%–23.6% of patients using two a priori decision rules. The frequency of individual NP events varied from 47.1% (headache) to 0% (myasthenia gravis). The outcome was significantly better for those NP events attributed to SLE especially if they occurred within 1.5 years of the diagnosis of SLE. Patients with NP events, regardless of attribution, had significantly lower summary scores for both mental and physical health over the study.
Conclusions
NP events in SLE patients are variable in frequency, most commonly present early in the disease course and adversely impact patients’ quality of life over time. Events attributed to non-SLE causes are more common than those due to SLE, although the latter have a more favourable outcome.
doi:10.1136/ard.2008.106351
PMCID: PMC2929162  PMID: 19359262
Lupus; Neuropsychiatric; Prospective; Inception cohort
6.  Prolonged complete remission in previously severe SLE. 
Of 160 patients with systemic lupus erythematosus followed up in a long-term prospective study 4 with previously severe disease are in complete remission and have required no therapy for a median time of 75 months. The 4 females all presented with systemic features and a typical butterfly rash prompting early diagnosis and treatment. All patients have had complete remission of clinical and laboratory features of disease, without maintenance suppressive therapy.
PMCID: PMC1000861  PMID: 7065728
7.  Peripheral vascular disease in patients with systemic lupus erythematosus. 
Patients with systemic lupus erythematosus may develop premature atherosclerosis, notably coronary artery disease. A group of 10 patients with peripheral vascular disease presenting with intermittent claudication or gangrene were studied from a group of 563 patients followed prospectively at the Wellesley Hospital Lupus Clinic. These 10 patients were compared with the next lupus clinic patient matched for age and sex, with respect to demographic characteristics and risk factors. The patients and controls did not differ significantly in lupus activity criteria count, partial thromboplastin time, the number with antibody to cardiolipin, number receiving steroids or mean steroid dose, family history of atherosclerosis, hyperlipidaemia, smoking, hypertension or use of oral contraceptives. The risk factors for developing peripheral vascular disease were a longer duration of systemic lupus erythematosus and a longer duration of use of steroids. Eight of the 10 patients had coexistent coronary artery disease or transient ischaemic attack.
PMCID: PMC1004619  PMID: 1540039
10.  Brain scan diagnosis of central nervous system involvement in systemic lupus erythematosus. 
Annals of the Rheumatic Diseases  1978;37(4):357-362.
Twenty-five patients with 29 episodes of active systemic lupus erythematosus with central nervous system involvement were studied according to a uniform protocol. Brain scans were found to be abnormal in all patients studied, and electroencephalograms were abnormal in 20/25 patients. Serial brain scanning was found to be useful in the diagnosis of exacerbations and the monitoring of corticosteroid dosage.
Images
PMCID: PMC1000244  PMID: 686868
11.  Felty's syndrome. Clinical and serological analysis of 34 cases. 
Annals of the Rheumatic Diseases  1977;36(6):500-507.
Review of 34 cases of Felty's syndrome showed this to be a form of 'super' rheumatoid disease because of the severity of joint disease, the prominence of extra-articular features and the remarkable incidence of infection. The response to splenectomy in these 34 patients was shown by a return towards normal of peripheral blood abnormalities and a decrease in bone marrow granulopoiesis. Although some patients remained free of infection after splenectomy, others have continued to have infections despite the return of white blood cell counts to normal levels. Although splenectomy and subsequent increase in white blood cell levels may be beneficial, our experience suggests that other factors are important in the susceptibility to infection of Felty's syndrome patients. Moreover, we think that splenectomy may have been instrumental in the fatal infection of one of our patients.
PMCID: PMC1000154  PMID: 596944
12.  Laboratory Tests for Diagnosing Connective Tissue Diseases 
Canadian Family Physician  1971;17(12):49-50.
The author describes three most useful groups of laboratory tests for connective tissue disease — hemogram, acute phase reactants and immune factors. Since most of these tests are relatively non-specific, the most valuable assets for arriving at the correct diagnosis of a connective tissue disease are still a complete history, thorough physical examination and a good knowledge of the course of the disease. Newer laboratory tests can then serve as adjuncts in confirming the diagnosis or following the course of the disease.
PMCID: PMC2370287  PMID: 20468709
13.  Selective C4 deficiency, systemic lupus erythematosus, and Whipple's disease. 
A 45-year-old female with selective deficiency of C4 and systemic lupus erythematosus developed puzzling gastrointestinal and systemic symptoms in the last 6 months of her life. Extensive investigation of the gastrointestinal tract did not yield any diagnosis, and the patient died shortly afterwards. Autopsy revealed evidence of a typical Whipple's disease of the jejunum and lymph nodes. This association has not been previously described. The disease is reviewed with emphasis on its being an opportunistic infection in an immunosuppressed host with a complement deficiency and SLE.
Images
PMCID: PMC1001230  PMID: 6198977
14.  Long-term effects of azathioprine in rheumatoid arthritis. 
Annals of the Rheumatic Diseases  1982;41(Suppl 1):18-22.
Efficacy and safety of azathioprine in 'high' and 'low' dose regimens in rheumatoid arthritis (RA), both in short-term studies and in follow-up over 40 months, have previously been shown. In the present report, 36 patients with RA treated with azathioprine (group I) and 49 age-matched patients with RA (group II), were studied to detect potential early markers of malignancy. Chest x-rays were similar to both groups. One patient in group I had a positive PAP smear and was subsequently found to have uterine carcinoma. Alpha-fetoprotein was positive in one patient in group I and none in group II. CEA was negative in all patients in group I, but positive in seven in group II. On chromosomal analysis group I showed a greater frequency of breakage. Group I showed lower serum folates and a highly significant number of megaloblastic features in marrow aspirates. In group I seven tumours, three being malignant, occurred while taking azathioprine, and in group II six tumours, one malignant, were identified (p = 0.17). The apparent increased risk of malignancy previously suggested by others warrants further studies with larger populations and over a continuous longer period.
PMCID: PMC1030287  PMID: 6175283
15.  Central retinal vein occlusion and scleroderma: implications for sclerodermatous vascular disease. 
A patient with scleroderma (progressive systemic sclerosis) who developed central retinal vein occlusion is described. The aetiology of this condition is discussed and the role of possible sclerodermatous vascular disease is highlighted. It is suggested that studies of fundal vasculature could be useful in the clinical assessment of sclerodermatous vascular disease.
Images
PMCID: PMC1000667  PMID: 7469533
16.  Venous syndromes and pulmonary embolism in systemic lupus erythematosus. 
Annals of the Rheumatic Diseases  1980;39(4):340-343.
Deep vein thrombophlebitis (DVT) and pulmonary emboli (PE) have been uncommonly reported manifestations of systemic lupus erythematosus (SLE). This may be partly due to their being masked by other more familiar lesions of the lungs and extremities in SLE. We have identified 17 patients with SLE from a population of 180 being followed up prospectively who had 21 attacks of DVT and/or PE. Of the total of 21 episodes the SLE was considered to be active in 14, inactive in 6, and variable in a patient with recurring phlebitis. The incidence of hyperlipidaemia, smoking history, and use of birth control medication or corticosteroids was not higher in these patients. These clinical findings thus constitute additional features of SLE occurring in about 9% of patients and may be significance for morbidity and mortality.
PMCID: PMC1000553  PMID: 7436559
17.  Leucapheresis in severe rheumatoid arthritis. 
Two patients with severe seropositive rheumatoid arthritis previously unresponsive to conventional therapy have been treated with leucapheresis. This technique involves continuous cell separation daily to remove primarily lymphocytes. Clinical improvement was recorded with the use of standard rheumatological measures of inflammation. It is concluded that leucapheresis may help in the management of severely active rheumatoid arthritis when conventional therapy has been unsuccessful.
PMCID: PMC1000316  PMID: 434945
20.  The Treatment of Gout and Disorders of Uric Acid Metabolism with Allopurinol 
Canadian Medical Association Journal  1966;95(22):1120-1127.
Allopurinol (4-hydroxypyrazolo (3,4-d)-pyrimidine) is a potent xanthine oxidase inhibitor which inhibits the oxidation of naturally occurring oxypurines, thus decreasing uric acid formation. The clinical and metabolic effects of this agent were studied in 80 subjects with primary and secondary gout and other disorders of uric acid metabolism. Allopurinol has been universally successful in lowering the serum uric acid concentration and uric acid excretion to normal levels, while not significantly affecting the clearance of urate or other aspects of renal function. Oxypurine excretion increased concomitantly with the fall in urine uric acid. The agent is particularly valuable in the management of problems of gout with azotemia, acute uric acid nephropathy and uric acid urolithiasis. The minor side effects, clinical indications and theoretical complications are discussed.
PMCID: PMC1935821  PMID: 5923471
22.  Postdiarrheal arthropathy of Yersinia pseudotuberculosis. 
Two patients with acute gastroenteritis in whom polyarthritis subsequently developed were found to have positive serologic results for Yersinia pseudotuberculosis. With resolution of the arthropathy the antibody titres decreased. While the patient without the histocompatibility antigen HLA-B27 had an acute, self-limited arthritis, the patient with this antigen had a more chronic arthritis. Serologic typing and stool culture for Y. pseudotuberculosis should be done in cases of postdysenteric arthritis.
PMCID: PMC1818014  PMID: 343903

Results 1-22 (22)