Uveitis and arthritis induced by adjuvant: clinical, immunologic and histologic characteristics

The intradermal administration of complete Freund's adjuvant (CFA) containing Mycobacterium butyricum to Sprague-Dawley (SD) and Lewis strain rats results in polyarthritis and uveitis. Over 90% of the eyes examined from the SD rats given CFA had histologic evidence of anterior uveitis, clinically evident in only 20 to 28%. Many rats developed arthritis without clinical uveitis, but uveitis was rare in the absence of arthritis. Histologically, the ocular inflammation was characterized by a polymorphonuclear, and later, a lymphocytic infiltration of the iris and ciliary body with cells and fibrinous exudate in the anterior chamber and cells in the vitreous. Antibodies and cellular immunity to ocular (S antigen, alpha crystallin), articular (type II collagen, proteoglycan) and bacterial components (MDP), were demonstrated in some rats, but positive tests did not correlate with either articular or ocular disease. Ten percent of rats given type II collagen in incomplete Freund's adjuvant developed uveitis. Thus, the pathogenesis of the arthritis and uveitis in the adjuvant model may be mediated by lymphocytes which exhibit crossreactivity with antigens in these structures, although the specificity of such antigens has not been identified in our studies.     

Use of aspirin, beta-blockers, and lipid-lowering medications before recurrent acute myocardial infarction: missed opportunities for prevention?

BACKGROUND: For patients who have had a previous myocardial infarction (MI), the use of aspirin, beta-blockers, and lipid-lowering agents reduces the risk of recurrent MI and death. OBJECTIVE: To examine trends in and determinants of receipt of these 3 medications before hospitalization for recurrent acute MI (AMI). METHODS: The study population consisted of 1710 patients with a previous history of MI hospitalized with a validated recurrent AMI in all hospitals in Worcester, Mass, during 1986, 1988, 1990, 1991, 1993, and 1995. Logistic regression analyses were used to assess the effect of demographic, clinical, and temporal factors on the receipt of aspirin, beta-blockers, and lipid-lowering medications before hospital admission for recurrent AMI. RESULTS: More than 47% of patients in each study year were not receiving each medication before admission, although significant increases in use were noted over time for aspirin (from 13.5% to 52.6%), beta-blockers (from 33.2% to 44.4%), and lipid-lowering medications (from 0.8% to 11.7%). In multivariate analyses, advancing age was associated with not receiving aspirin (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.51-0.89), lipid-lowering medications (OR, 0.14; 95% CI, 0.08-0.25), and beta-blockers (OR, 0.75; 95% CI, 0.57-1.00), although this effect was of borderline significance for beta-blockers. Being a woman was associated with not receiving aspirin (OR, 0.78; 95% CI, 0.62-0.98) but was positively associated with receiving lipid-lowering medications (OR, 1.59; 95% CI, 1.04-2.43). Coexisting medical conditions and concurrent use of other cardiovascular medications were also associated with receipt of each medication. CONCLUSION: Despite encouraging increases over time, the low absolute levels of receipt of medications shown to be efficacious in the long-term treatment of patients after an MI, and their variation by age and sex, suggest that substantial opportunities may exist to prevent recurrent AMIs through the increased use of aspirin, beta-blockers, and lipid-lowering medications.     

Risk of proximal colorectal neoplasia among asymptomatic patients with distal hyperplastic polyps

PURPOSE: Many guidelines on colorectal cancer screening do not consider distal hyperplastic polyps to be a marker for proximal neoplasia. However, 11 of 17 published studies have shown an increased risk of proximal neoplasia in patients with distal hyperplastic polyps. Our goal is to assess the risk of proximal neoplasia in asymptomatic patients with distal hyperplastic polyps, compared to those with distal tubular adenomas or no distal polyps. METHODS: We assessed proximal (cecum, ascending, transverse colon and splenic flexure) and distal polyps in patients undergoing screening colonoscopy, classifying them into 3 groups: distal hyperplastic polyps only; distal adenomas with or without hyperplastic polyps; no distal polyps. The prevalence of proximal neoplasia and advanced neoplasia (polyps > or =1 cm, villous adenomas, or cancer) was compared among these groups. RESULTS: Of 2357 patients, 427 (18%) had neoplasia, including 103 (4%) with advanced neoplasia. Proximal neoplasia occurred in 175 (9%) of 1896 patients with no distal polyps, compared with 28 (12%) of 237 with distal hyperplastic polyps (P = 0.20) and 64 (29%) of 224 with distal adenomas (P <0.0001). Proximal advanced neoplasia occurred in 39 (2%) patients with no distal polyps, compared with 4 (2%) with distal hyperplastic polyps (P = 0.70) and 9 (4%) with distal adenomas (P = 0.13). CONCLUSIONS: Patients with distal hyperplastic polyps, unlike those with distal adenomas, do not exhibit an increased risk for proximal neoplasia or proximal advanced neoplasia compared to those with no distal polyps. The discovery of hyperplastic polyps on screening sigmoidoscopy should not prompt colonoscopy.     

Adult “idiopathic” extrahepatic venous thrombosis

The etiology of extrahepatic venous obstruction (EHVO) is unknown in 50% of cases. Recently the presence of a latent myeloproliferative disorder has been reported in adults with idiopathic EHVO. We evaluated the course of these patients to establish if any putative latent myeloproliferative disorder influenced the clinical course compared to those with a known cause. Among 132 EHVO patients, 78 (59%) had a known etiology, 7 (5%) with an overt myeloproliferative disorder. The idiopathic group had 54 patients; 24 (13 men, 11 women) were diagnosed after 15 years of age, (median 38 years, range 17–70) with a median follow up of 96 months (19–372). Only 2 (8%) developed an overt myeloproliferative disorder. These 24 had a similar pattern of bleeding and onset of ascites as those with known cause. In EHVO failure to diagnose a latent myeloproliferative disorder does not influence the course of variceal bleeding, and thus has little prognostic significance.Supported by R Farini Foundation for Gastroenterology Research.     

The natural history of a genetic subtype of arrhythmogenic right ventricular cardiomyopathy caused by a p.S358L mutation in TMEM43

To determine the phenotype and natural history of a founder genetic subtype of autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by a p.S358L mutation in TMEM43. The age of onset of cardiac symptoms, clinical events and test abnormalities were studied in 412 subjects (258 affected and 154 unaffected), all of which occurred in affected males significantly earlier and more often than unaffected males. Affected males were hospitalized four times more often than affected females (p ≤ 0.0001) and died younger (p ≤ 0.001). The temporal sequence from symptoms onset to death was prolonged in affected females by 1–2 decades. The most prevalent electrocardiogram (ECG) manifestation was poor R wave progression (PRWP), with affected males twice as likely to develop PRWP as affected females (p ≤ 0.05). Left ventricular enlargement (LVE) occurred in 43% of affected subjects, with 11% fulfilling criteria for dilated cardiomyopathy. Ventricular ectopy on Holter monitor was common and occurred early: the most diagnostically useful clinical test. No symptom or test could rule out diagnosis. This ARVC subtype is a sex‐influenced lethal arrhythmogenic cardiomyopathy, with a unique ECG finding, LV dilatation, heart failure and early death, where molecular pre‐symptomatic diagnosis has the greatest clinical utility.