The role of RAS in the pathogenesis of preeclampsia

Preeclampsia is a hypertensive disorder that is unique to pregnancy, with consistent involvement of the kidney. The renin-angiotensin system (RAS) has been implicated in the pathogenesis of preeclampsia. In the gravid state, in addition to the RAS in the kidney, there is a tissue-based RAS in the uteroplacental unit. Increased renin expression in human preeclampsia and in transgenic mouse models with a human preeclampsia-like syndrome shows that activation of the uteroplacental RAS, with angiotensin II entering the systemic circulation, may mediate the pathogenesis of preeclampsia. Vascular maladaptation in preeclampsia with increased vasomotor tone, endothelial dysfunction, and increased sensitivity to angiotensin II and norepinephrine in manifest preeclampsia may be explained on the basis of angiotensin II-mediated mechanisms through angiotensin receptor type I (AT1) activation. Recently, novel angiotensin II-related biomolecular mechanisms have been described in preeclampsia. These include AT1 and bradykinin B2 receptor heterodimerization and the production of autoantibody against AT1. Various organ systems with predilection for involvement in preeclampsia are sites of tissue-based RAS. Angiotensin II-mediated mechanisms may explain the primary clinicopathologic features of preeclampsia. In this review, these various aspects are critically examined and an integrated concept on the role of RAS in preeclampsia is presented.     

Adequacy of mucosal sampling with the "two-bite" forceps technique: a prospective,randomized, blinded study

BACKGROUND: Although the "two-bite" technique (obtaining 2 mucosal biopsy specimens with a single passage of the forceps) is used routinely, the adequacy of the second biopsy for histopathologic examination has not been evaluated. Our hypothesis was that the second sample will be inadequate for this purpose. The aim of this study was to prospectively assess the adequacy of mucosal biopsy specimens obtained with 3 different types of forceps with the two-bite technique. METHODS: Patients undergoing diagnostic EGD were prospectively enrolled in the study. In each patient, mucosal biopsy specimens were obtained as follows: 4 specimens with the two-bite technique in 2 separate passages of the forceps (one from the esophagus followed by one from the stomach, and one from the stomach followed by one from the esophagus, the order being chosen randomly) and 2 single-bite specimens from the same anatomic locations (esophagus and stomach). Each patient underwent the same biopsy sampling sequence with 3 different forceps. An experienced pathologist blinded to the sequence and technique of obtaining the samples and the forceps used evaluated the specimens for number submitted, integrity, and adequacy for histopathologic diagnosis and depth of the sample as assessed by the presence or absence of muscularis mucosae. RESULTS: A total of 288 mucosal samples were obtained from 16 patients. Of these, 192 were taken by using the two-bite technique. Thirty-five (18.2%) samples were missing when the two-bite technique was used compared with only 2 (2.1%) when the single bite technique was used (p < 0.05). Irrespective of the location from which the first mucosal sample was taken, a significantly greater number of first samples were lost (25%) compared with second samples (11.5%) (p < 0.05). The forceps without a spike was associated with significantly more missing samples than the spiked forceps (28.1% vs. 13.3%; p = 0.01). At histopathologic evaluation, there were no significant differences between first and second samples nor differences between samples taken with the two-bite and the single-bite techniques with regard to adequacy, integrity, and depth. With respect to histopathologic evaluation, there were no differences among the 3 types of forceps used in the study. CONCLUSIONS: Although the second mucosal sample obtained with the two-bite technique is adequate for histopathologic purposes, there is a significant risk of losing samples (the first one in particular) with this technique, and thus an increase in the probability of sampling error. This may be particularly true for forceps without a spike.