Thiopurine methyltransferase activity combined with 6-thioguanine metabolite levels predicts clinical response to thiopurines in patients with inflammatory bowel disease.

BACKGROUND/AIMS: 6-Mercaptopurine and its prodrug azathioprine are effective for the treatment of inflammatory bowel disease. Thiopurine methyltransferase is important for the metabolism of thiopurines. However, there is controversy as to the clinical utility of measuring thiopurine methyltransferase enzyme activity and 6-thioguanine nucleotide levels. Our aim was to determine if thiopurine methyltransferase enzyme activity and 6-thioguanine nucleotide level monitoring would predict response to therapy with thiopurines in patients with inflammatory bowel disease. METHODS: Baseline thiopurine methyltransferase enzyme activity prior to initiation of therapy with either 6-mercaptopurine or azathioprine was determined in 39 patients with inflammatory bowel disease. The association between clinical response and thiopurine methyltransferase activity and 6-thioguanine nucleotide levels singly or in combination were analysed. RESULTS: Seventeen of 39 patients (44%) responded to 6-mercaptopurine or azathioprine therapy. Thiopurine methyltransferase enzyme activity below the mean of 30.5 U was significantly associated with clinical response. The thiopurine methyltransferase low phenotype was associated with response in 65% vs. 29% in individuals with thiopurine methyltransferase enzyme activity above 30.5 U (p = 0.05). There was no correlation between thiopurine methyltransferase activity and 6-thioguanine nucleotide levels. The maximal 6-thioguanine nucleotide levels did not predict clinical response. When combining thiopurine methyltransferase enzyme activity and 6-thioguanine nucleotide levels, the combination of thiopurine methyltransferase low/6-thioguanine nucleotide high was associated with response in 7/7 (100%) vs. only 2/8 (25%) with the combination of thiopurine methyltransferase high/6-thioguanine nucleotide low (p=0.01). CONCLUSIONS: Thiopurine methyltransferase activity inversely correlated with clinical response to thiopurine treatment in inflammatory bowel disease. Thiopurine methyltransferase enzyme activity below 30.5 U combined with a post-treatment 6-thioguanine nucleotide level > 230 pmol/8 x 10(8) erythrocytes was the best predictor of response.

Aortic root dilatation in patients with emphysema.

BACKGROUND: Abdominal aortic aneurysms have been recognized to occur more frequently in patients with emphysema. However, the prevalence of aortic root dilatation in patients with emphysema and its relationship to risk factors for aortic enlargement have not been previously described. METHODS: We studied 47 patients, past smokers (aged 67 +/- 6 years, 18 women) with severe emphysema diagnosed by a pulmonary function test and an ultrafast computed tomographic scan. Two-dimensional echocardiography was used to measure the aortic root at the aortic annulus, sinus of Valsalva, sinotubular junction and proximal part of the ascending aorta. Measured mean values were compared with published normal values and age- and sex-matched patients without emphysema. The relationship between aortic root size and cardiac risk factors (hypertension, hypercholesterolemia, and diabetes) was also examined. RESULTS: In patients with emphysema the mean aortic root dimensions were significantly larger than normal values at each measured site (P <.0001) and those of patients without emphysema (P <.05 to.0001). A substantial percentage of patients with emphysema had larger sinus of Valsalva (43%) and proximal ascending aorta (59%) than the upper limit of normal. In the multivariable regression model, emphysema was a significant determinant of aortic root size at all measured sites and hypertension was associated with additional dilatation at the sinus of Valsalva, sinotubular junction, and proximal ascending aorta. CONCLUSIONS: (1) In patients with emphysema the aortic root dimension is significantly larger than in patients without emphysema. (2) Systemic hypertension is associated with additional enlargement of the proximal ascending aorta, the sinus of Valsalva, and the sinotubular junction.

A multi-disciplinary curriculum for 11- to 13-year-olds: immunization, plus!

A sixth grade curriculum entitled "Immunization, Plus!" Was developed to promote adolescent immunization. This targeted immunization curriculum utilized contemporary learning theory and innovative teaching approaches and styles to maximize acceptability among educators. Because instructional time in school was limited, a thematic curriculum was created to embed immunization and communicable disease content within mathematics, science/health, and language arts units. The curriculum, which reflected the theory of multiple intelligences among students, offered an array of different learning formats, including linguistic, logical-mathematical, spatial, and bodily-kinesthetic. The curriculum was made available free of charge to school districts in California, and its evaluation was planned to track distribution, utilization, and changes in students' knowledge, attitude, and behavior.