Rodanthi C. Kitridou

Synergistic effect between IL-10 and bcl-2 genotypes in determining susceptibility to systemic lupus erythematosus

OBJECTIVE To determine whether genes participating in programmed cell death, including bcl-2, IL-10, Fas-L, and CTLA-4, may contribute to the genetic predisposition to systemic lupus erythematosus (SLE). METHODS First, intragenic markers for the bcl-2, IL-10, Fas-L, and CTLA-4 genes were characterized and their extent of polymorphism in normal populations was determined. The allelic distribution of these gene markers in a large Mexican American SLE cohort of 158 patients and 223 ethnically matched controls was determined using fluorescent-labeled primers and semiautomated genotyping. RESULTS The bcl-2, Fas-L, and IL-10 loci showed significantly different allelic distribution in SLE patients compared with controls, indicating an association between these genes and SLE. No association was found between SLE and the CTLA-4 gene. Further analysis revealed a synergistic effect between susceptibility alleles of the bcl-2 and IL-10 genes in determining disease susceptibility. Alone, the presence of each of these alleles was associated with a moderate increase in SLE risk, while the occurrence of these alleles together increased the odds of developing SLE by more than 40-fold. CONCLUSION The results suggest that individuals carrying specific genotypes of both bcl-2 and IL-10 are at significant risk of developing SLE.

Surgical procedures in the management of Takayasu's arteritis

Takayasus arteritis is an inflammatory arteriopathy that often progresses to obliteration of multiple large arteries. Variable results have been reported after medical and surgical management. Twenty female patients with Takayasus arteritis were treated from 1973 to 1989. Eleven (55%) patients had hypertension. Upper or lower extremity ischemia was present in 12 (60%) patients and cerebrovascular insufficiency in seven (35%). Nine patients initially managed with corticosteroids had no improvement in signs or symptoms of arterial insufficiency. Eleven patients had 16 vascular procedures for the following indications: renovascular hypertension (6), extremity ischemia (5), cerebrovascular insufficiency (2), dilation ascending aorta with aortic insufficiency (1), thoracic aortic aneurysm (1), abdominal aortic aneurysm (1). Procedures included aortorenal bypass (5), carotid-subclavian, axillary, or brachial bypass (4), aorto-carotid bypass (2), aneurysm resection (2), supra-celiac aorto-femoral bypass (1), ascending aorta/aortic valve replacement (1), and nephrectomy (1). Clinical improvement occurred in all patients. There were no operative deaths. All are alive at a mean follow-up of 5.75 years (6 months to 16 years). Revision of the initial reconstruction has been required for recurrent renovascular hypertension in one patient and extremity ischemia in another. The other nine patients remain symptomatically improved. Symptomatic Takayasus arteritis frequently requires arterial reconstruction. Symptomatic improvement and excellent long-term graft patency can be expected after arterial reconstruction.

Esophageal dysfunction in patients with mixed connective tissue diseases and systemic lupus erythematosus.

We sought to correlate esophageal symptoins with esophaged motility abnormality in 17 patients with mixed connective tissue disease (MCTD) and in 14 patients with systemic lupus erythematosus (SLE). Heartburn and regurgitation were common symptoms (11/17) in patients with MCTD, and most of them (10/11) exhibited significant manometric abnormalities. Additionally, impairment of esophageal peristalsis was found in four of the remaining asymptomatic patiens. Severe esophageal aperistalsis was noted in nine MCTD patients. Patients with SLE also frequently reported esophageal symptoms (8/14), but significant motility abnormalities were seen in only three cases. In both patient groups good correlation between Raynauds phenomenon and esophageal aperistalsis was found. Our results reveal that, although esophageal symptoms are commonly present in patients with both MCTD and SLE, severe esophageal motility abnormalities are more often found in patients with MCTD than in those with SLE.

Renal Involvement in Mixed Connective Tissue Disease: A Longitudinal Clinicopathologic Study

Eleven of 30 patients with MCTD, followed for a mean of 10 years, developed immune complex nephropathy (five membranous, two mesangial, one mixed, and one sclerosing) with NS in nine of 11. Another patient had membranous nephropathy at autopsy. Patients with renal disease tended to have more systemic manifestations than those without. NS was at times of abrupt onset, recurrent, and/or persistent. Anti-RNP and serum complement were not helpful in predicting nephritis. Seventy-two percent of nephropathy and 62% of NS episodes resolved or improved after corticosteroid therapy. Five patients became hypertensive, two developed chronic renal failure and required chronic dialysis, and one needed acute dialysis twice. One patient progressed to focal proliferative crescentic nephritis with necrotizing arteritis. Three patients with nephropathy died, two of pulmonary hypertension with acute cor pulmonale and one of overwhelming sepsis. Nephropathy is relatively common in MCTD, is associated with substantial morbidity, and with the risk of hypertension and chronic renal failure.

The efficacy and safety of single daily doses of oxaprozin in the treatment of rheumatoid arthritis: A comparison with aspirin

The efficacy and safety of Oxaprozin (1,200 mg once daily) and aspirin (975 mg four times daily) were compared in a 6-month double-blind, multicenter investigation of 218 patients with active rheumatoid arthritis (RA). Both treatment groups showed statistically significant improvement from baseline in measures of joint tenderness and swelling, morning stiffness, right- and left-hand grip strength, time to walk 50 feet, and the opinions of the observers and the patients. The therapeutic index, which is based on the observers opinion and includes the effect of treatment-related discontinuations, was 48% for the oxaprozin-treated patients compared with 26% for those treated with aspirin (P