A prospective study of NAT2 acetylation genotype, cigarette smoking, and risk of breast cancer

Polymorphisms in the N-acetyltransferase 2 (NAT2) gene are determinants of the rate of metabolic activation of carcinogenic compounds such as aryl aromatic amines. Homozygosity for any combination of three variant alleles in Caucasians defines 'slow' acetylators; presence of one or two wild-type alleles characterizes 'rapid' acetylators. Although most previous studies have not observed an overall elevation in risk of breast cancer among slow acetylators, a recent study observed that cigarette smoking was associated with a large increase in risk of breast cancer among slow acetylators. We assessed the relation between NAT2 acetylation status and breast cancer risk, and its interaction with smoking, in a prospective study of mainly Caucasian US women. Four hundred and sixty-six incident cases who were diagnosed with breast cancer after giving a blood specimen in 1989-90 were matched to 466 controls in a nested case-control study. NAT2 genotype was determined using PCR-RFLP assays. The multivariate relative risk (RR) comparing slow with rapid acetylators was 0.9 (95% CI 0.7-1.2). Among slow acetylators, current smoking immediately prior to diagnosis was not associated with a significant elevation in risk compared with never smoking rapid acetylators (RR = 1.4, 95% CI 0.7-2.6). No significant association was seen between pack-years of smoking and risk of breast cancer among either slow or fast acetylators. A non-significant elevation in risk was observed among women who smoked for > or = 5 years prior to first pregnancy and were rapid acetylators, compared with never smoking rapid acetylators (RR = 1.5, 95% CI 0.9-2.6). In analyses limited to 706 post-menopausal women, the elevated risks for current smokers immediately prior to diagnosis who were slow acetylators compared with never smokers who were fast acetylators were slightly stronger but still not statistically significant. In summary, we observed little evidence of an association between NAT2 genotype and breast cancer. In this prospective study, cigarette smoking was not appreciably associated with breast cancer among either slow or fast NAT2 acetylators.      

A prospective randomized trial of the surgical blood order equation for ordering red cells for total hip arthroplasty patients

BACKGROUND: The majority of crossmatched blood is for surgical patients, and most of it is never transfused. An alternative system for ordering red cell (RBC) units, called the surgical blood order equation (SBOE), which incorporates specific patient variables for surgical patients, has been developed. STUDY DESIGN AND METHODS: A prospective double-blind randomized trial compared the SBOE with the maximal surgical blood order schedule (MSBOS) system for ordering allogeneic RBC units in 60 patients undergoing total hip arthroplasty. Autologous RBCs were available for none of the patients. RESULTS: There were no differences in patient demographic, surgical, or laboratory variables at any time. The median number (range) of allogeneic RBC units ordered was 2 (2-3) for the MSBOS and 0 (0-3) for the SBOE (p<0.0001). The SBOE ordered the correct number of RBC units for 58 percent of patients, while the MSBOS did so for 7 percent (p<0.0001). The SBOE had a lower crossmatch-to-transfusion ratio than the MSBOS (0.83 vs. 4.12). Costs were also lower with the SBOE. CONCLUSION: Incorporation of patient factors in the use of the SBOE system resulted in increased efficiency of blood-ordering practices for total hip arthroplasty.     

Gastric adenocarcinoma: CT versus surgical staging

Seventy-five patients with gastric carcinoma underwent preoperative staging with computed tomography (CT). In 14 patients, CT failed to demonstrate lymphadenopathy despite the presence of malignant lymph nodes at surgery. In 13 patients, CT demonstrated enlarged nodes, but no malignant involvement was found at surgery. Although spread to the pancreas was correctly predicted in three patients with lack of fat plane between tumor and pancreas, five patients lacking a fat plane had no invasion, whereas eight patients with an intact fat plane had invasion. Thirty-five patients (47%) were incorrectly staged with CT:23 (31%) were understaged and 12 (16%) were overstaged. CT does not accurately display the true extent of disease in patients with gastric carcinoma and therefore should not be used routinely for staging.     

Magnetic resonance imaging in the diagnosis of breast disease: use of transverse relaxation times

The ability of magnetic resonance imaging (MR) to demonstrate breast carcinoma depends upon significantly different relaxation times in benign and malignant tissues. The authors conducted an in vitro study of transverse relaxation times (T2) of 393 breast tissue samples in order to establish a range of values for normal tissue, benign lesions, and carcinoma. All T2 values were multiexponential. Benign lesions were readily distinguished from both invasive and noninvasive carcinoma in samples containing fat or a mixture of fat and fibrous tissue; however, in purely fibrous samples there was some overlap of T2 values in benign and malignant tissues. Although the data acquisition and analysis requirements involved in this in vitro study exceed the capabilities of present whole-body MR imagers, the added understanding gained through efforts of this type may aid both interpretation of current images and future developments.     

Nephrolithiasis and risk of hypertension in women

Cross-sectional and prospective studies of men suggest a positive association between nephrolithiasis and hypertension. However, this association remains controversial in women. We conducted a prospective study of the relation between nephrolithiasis and the risk for hypertension in the Nurses' Health Study, a cohort of 89,376 women aged 34 to 59 years in 1980. Information on the history of nephrolithiasis, physician-diagnosed hypertension, and other relevant exposures was obtained by biennial mailed questionnaire. A history of nephrolithiasis before 1980 was reported by 2,558 women (2.9%), and a history of hypertension was reported by 11,883 women (13.3%). Among women without hypertension before 1980, 12,540 women reported a new diagnosis of hypertension between 1980 and 1992, during 711,039 person-years of follow-up. Compared with those without a history of nephrolithiasis, the age-adjusted relative risk (RR) for incident hypertension in women with such a history was 1.36 (95% confidence interval [CI], 1.20 to 1.43). After further adjustment for body mass index (BMI) and the intake of calcium, sodium, potassium, magnesium, caffeine, and alcohol, the RR was only slightly attenuated (RR=1.24; 95% CI, 1.13 to 1.37). In contrast, the occurrence of incident nephrolithiasis during follow-up was similar in women with hypertension at baseline compared with women without (adjusted odds ratio [OR]=1.01; 95% CI, 0.85 to 1.20). These data are consistent with the results obtained in men and support the hypothesis that a history of nephrolithiasis is associated with an increased risk for subsequent hypertension. Dietary factors, such as the intake of calcium, sodium, and potassium, do not explain this association. Unidentified pathogenic mechanisms common to nephrolithiasis and hypertension may be responsible for the development of both disorders.