INTRODUCTION (RAIR) Recto-anal inhibitory reflex is an integral part of normal defecation. The physiological characteristics of RAIR along anal length and anterior-posterior axis are unknown. AIM To perform topographic and vector-graphic evaluation of RAIR along anal canal using high definition manometry (HDM), and examine the role of various muscle components. METHODS Anorectal topography was assessed in 10 healthy volunteers using HDM probe with 256 sensors. RAIR data were analyzed every mm along the length of anal canal for topographic, baseline, residual, and plateau pressures during 5 mean volumes of balloon inflation (15cc, 40cc, 71cc, 101cc, 177cc), and in 3D by dividing anal canal into 4×2.1 mm grids. RESULTS Relaxation pressure progressively increases along anal canal with increasing balloon volume up to 71 cc and thereafter plateaus. In 3-D, RAIR is maximally seen at the middle and upper portions of anal canal (levels 1.2-3.2 cm) and posteriorly. Peak residual pressure was seen at proximal anal canal. CONCLUSION RAIR is characterized by differential anal relaxation along Anterior-Posterior axis, longitudinally along the length of anal canal, and it depends on the rectal distention volume. It is maximally seen at internal anal sphincter pressure zone. Multidimensional analyses indicate that external anal sphincter provides bulk of anal residual pressure. Our findings emphasize importance of sensor location and orientation; as anterior and more distal location may miss RAIR.

Desire to defecate is associated with a unique anal contractile response, the sensorimotor response (SMR). However, the precise muscle(s) involved is not known. We aimed to examine the role of external and internal anal sphincter and the puborectalis muscle in the genesis of SMR. Anorectal 3-D pressure topography was performed in 10 healthy subjects during graded rectal balloon distention using a novel high-definition manometry system consisting of a probe with 256 pressure sensors arranged circumferentially. The anal pressure changes before, during, and after the onset of SMR were measured at every millimeter along the length of anal canal and in 3-D by dividing the anal canal into 4 ϫ 2.1-mm grids. Pressures were assessed in the longitudinal and anterior-posterior axis. Anal ultrasound was performed to assess puborectalis morphology. 3-D topography demonstrated that rectal distention produced an SMR coinciding with desire to defecate and predominantly induced by contraction of puborectalis. Anal ultrasound showed that the puborectalis was located at mean distance of 3.5 cm from anal verge, which corresponded with peak pressure difference between the anterior and posterior vectors observed at 3.4 cm with 3-D topography (r ϭ 0.77). The highest absolute and percentage increases in pressure during SMR were seen in the superior-posterior portion of anal canal, reaffirming the role of puborectalis. The SMR anal pressure profile showed a peak pressure at 1.6 cm from anal verge in the anterior and posterior vectors and distinct increase in pressure only posteriorly at 3.2 cm corresponding to puborectalis. We concluded that SMR is primarily induced by the activation and contraction of the puborectalis muscle in response to a sensation of a desire to defecate. anal manometry; puborectalis IN HUMANS, BALLOON DISTENTION of the rectum normally induces the recto-anal inhibitory reflex (RAIR) (6, 11) as well as the recto-anal contractile reflex (RACR) (9, 10, 21). RAIR is an enteric neuronal reflex that is mediated by nitric oxide, vasoactive intestinal peptide, and adenosine triphosphate and causes relaxation of internal anal sphincter (IAS) (18). The rate and method of rectal distention (intermittent vs. ramp) affect the properties of the RAIR, and this reflex response is classically absent in Hirschsprung's disease and other conditions such as after circular rectal myotomy and after lower anterior resection (4,12,22).In addition to the aforementioned reflexes, recently, we have described the sensorimotor response (SMR) (5) that is also seen during balloon distention of the rectum. The SMR is a transient anal contraction that is usually seen overlying the initial relaxation phase of the RAIR (5). In healthy subjects, it coincides with the onset of a sensation for defecation (5). A recent study showed that the SMR was abnormal in patients with rectal hyposensitivity, suggesting a pathophysiological role for this response in anorectal disorders (19). However, the precise origin of the anal contractile response, in particular...

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Cirrhotic explanted livers occasionally have unexpected periodic acid-Schiff-diastase (PASD)-positive globules within the hepatocyte cytoplasm. It is often unclear whether this finding is a nonspecific consequence of cirrhosis or is indicative of an underlying alpha-1-antitrypsin deficiency (A1ATD) contributing to the cirrhosis. In this study, explanted livers were retrospectively evaluated for histopathology (including PASD status with confirmatory alpha-1-antitrypsin [A1AT] immunohistochemistry [IHC]), and chart review provided etiology of liver failure and general clinical parameters. Real-time polymerase chain reaction was used to detect A1AT genotype (SERPINA1 S and Z alleles) by melting curve analysis on liver explant tissue from selected cases. Of 196 explanted livers, 21 (11%) had PASD+ globules, which were significantly enriched in patients with a clinical diagnosis of nonalcoholic steatohepatitis (NASH; 47%) compared with other causes (P < 0.001). IHC confirmed all PASD+ globules were A1AT+, with 20 of 21 cases demonstrating diffuse A1AT staining. In an expanded NASH cohort, 42% (14/33) of explants had PASD+ globules, 92% of which were homozygous (n = 1) or heterozygous (n = 11) for the SERPINA1 Z allele, corresponding to nearly 40% of all NASH patients. Overall, the Z allele was present in 10% of all tested liver explants, with 85% of PASD+ cases genotyping homozygous (n = 2) or heterozygous (n = 20), which is far in excess of the estimated 2% in the general population. These results indicate PASD+ A1AT globules (with confirmatory genotyping showing at least 1 Z allele) are commonly observed in NASH, suggesting a synergistic relationship toward liver fibrosis. In addition, the high frequency of SERPINA1 Z alleles in liver transplantation patients supports the utility of pretransplant genotyping.

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