Publications

OBJECTIVE

The objective of this study was to determine whether specific clinical symptoms associated with hematochezia are predictive of important GI pathology and whether full colonoscopic examination is necessary.

METHODS

A total of 103 outpatients (> or = 45 yr) with hematochezia, defined as the passage of bright red blood per rectum, underwent anoscopy and colonoscopy. Before endoscopy, patients completed a detailed interview, quantitating the amount and frequency of bleeding, weight loss, use of aspirin/NSAIDs, change in bowel habits, family history, and prior GI illnesses. Based on this information, physicians were asked to predict whether the bleeding was from a perianal or more proximal site. At colonoscopy, pathology was stratified as either proximal or distal to the sigmoid/descending junction. Substantial pathology was defined as one or more adenomas > 8 mm, carcinoma, or colitis.

RESULTS

Anoscopy demonstrated internal and external hemorrhoids in 78 and 29 patients, respectively. On colonoscopy, 36 patients had 43 substantial lesions. Thirty-seven of these lesions were distal to the junction of the descending and sigmoid colons and six were proximal lesions. Four patients had cancer; all were distal lesions. Patients with substantial lesions were more likely to give a history of blood mixed within their stool (p = 0.03), to have more episodes of hematochezia per month (p = 0.008), and to have a significantly shorter duration of bleeding before medical evaluation (p = 0.02) than did patients without such lesions. However, the physician's clinical assessment did not predict reliably which patients were likely to have substantial pathology.

CONCLUSIONS

In patients with hematochezia, clinicians were unable to distinguish between those patients with and those without significant colonic lesions by history alone. Flexible sigmoidoscopy would have demonstrated most (95%) substantial lesions. The lesions that flexible sigmoidoscopy missed were an unlikely cause of bleeding in this small group of patients.

Multiple observational studies suggest a marked reduction in risk of coronary heart disease (CHD) associated with postmenopausal estrogen use. A new meta-analysis presented here extends these results to estrogen plus progestin regimens. Although the findings from observational studies are strong and consistent, and there are several plausible mechanisms by which estrogen might reduce risk for CHD, most of the known biases would tend to exaggerate estrogen's benefit. Further, estrogen therapy clearly increases risk for endometrial hyperplasia and cancer, venous thromboembolic events and gallbladder disease, and long-term use probably also increases the risk of breast cancer. Therefore, until findings from randomized trials confirm and quantitate the benefit of estrogen therapy for prevention of CHD, we believe it should not be recommended to all postmenopausal women.

Studies of allogeneic lymphocyte cytotoxicity have shown that the rat NK allorecognition repertoire is controlled by genetic elements in both the MHC (RT1) and the NK gene complex (NKC). DA rats, possessing NK cells that are unable to lyse allogeneic lymphoblasts, were immunized with alloreactive NK cells from MHC-matched PVG.1AV1 rats, and two mAb, STOK1 and STOK2, were generated. STOK1 and STOK2 stained identical subsets of NKR-P1+ T and NK cells from certain strains of rats. Relative numbers varied markedly in a panel of MHC congenic strains, however, implicating a role for self MHC genes in their development. Both STOK1 and STOK2 immunoprecipitated a 110-kDa disulfide-linked homodimeric molecule, with extensive N-linked glycosylations, encoded by a gene that mapped to the NKC. NK cells expressing this glycoprotein displayed an increased ability to lyse allogeneic lymphoblasts, while syngeneic targets were spared. However, blockade of the STOK2 Ag with F(ab')2 of STOK2 permitted the NK lysis of syngeneic targets, but did not affect NK allorecognition. These results indicate that mAb STOK1 and STOK2 identify an NKC-encoded MHC receptor in the rat that acts as a negative regulator of cytotoxicity.