PubMed · 14364423
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C C JACKSON. 1955-05-01. Common rectal disorders.. https://pubmed.ncbi.nlm.nih.gov/14364423/
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Intra-anal malignancies disproportionately affect individuals who engage in anal intercourse because of infection with human papillomaviruses (HPVs), with an increased risk attributed to infection with HIV because of a declining immunity against HPVs. Long-term persistence of HPVs suggests yet other mechanisms that determine the clinical outcome, however. Because methylation of HPV DNA represses oncogene expression in cervical samples, we investigated whether this mechanism also occurs in HIV-positive men and studied the methylation of CpG dinucleotides overlapping with the HPV-16 enhancer and promoter in 16 anal samples. Similar to cervical infections, the average methylation frequency was 12.3%, with heterogeneities between clones from different and the same samples. In low-grade anal intraepithelial neoplasia (AIN), methylation was high in CpGs overlapping the viral enhancer but rare in promoter positions, whereas methylation was high in promoter regions in high-grade AIN, especially in samples with a high load of viral genomes. The viral replication origin was never methylated. We also detected de novo methylation at methylated (me) CpA, meCpT, and meCpC dinucleotides. Our study expands the observation and mapping of HPV DNA methylation to anal infections and the HIV-positive patient population. As observed at the cervix, DNA methylation may force HPVs into latency with functional replication but repressed transcription. Escape from this repression is a prerequisite for neoplastic progression; however, methylation resumes because of chromosomal integration of HPV genomes but spares some HPV genomes in each cell that maintain the transformed phenotype. DNA methylation, taken together with virus load, may be useful to diagnose the emergence of a population of tumor cells.
Nitric oxide (NO) relaxes the internal anal sphincter (IAS), but its enzymatic source(s) remains unknown; neuronal (nNOS) and endothelial (eNOS) NO synthase (NOS) isoforms could be involved. Also, interstitial cells of Cajal (ICC) may be involved in IAS relaxation. We studied the relative roles of nNOS, eNOS, and c-Kit-expressing ICC for IAS relaxation using genetic murine models. The basal IAS tone and the rectoanal inhibitory reflex (RAIR) were assessed in vivo by a purpose-built solid-state manometric probe and by using wild-type, nNOS-deficient (nNOS-/-), eNOS-deficient (eNOS-/-), and W/W(v) mice (lacking certain c-Kit-expressing ICC) with or without L-arginine or N(omega)-nitro-L-arginine methyl ester (L-NAME) treatment. Moreover, the basal tone and response to electrical field stimulation (EFS) were studied in organ bath using wild-type and mutant IAS. In vivo, the basal tone of eNOS-/- was higher and W/W(v) was lower than wild-type and nNOS-/- mice. L-arginine administered rectally, but not intravenously, decreased the basal tone in wild-type, nNOS-/-, and W/W(v) mice. However, neither L-arginine nor L-NAME affected basal tone in eNOS-/- mice. In vitro, L-arginine decreased basal tone in wild-type and nNOS-/- IAS but not in eNOS-/- or wild-type IAS without mucosa. The in vivo RAIR was intact in wild-type, eNOS-/-, and W/W(v) mice but absent in all nNOS-/- mice. EFS-induced IAS relaxation was also reduced in nNOS-/- IAS. Thus the basal IAS tone is largely controlled by eNOS in the mucosa, whereas the RAIR is controlled by nNOS. c-Kit-expressing ICC may not be essential for the RAIR.
BACKGROUND: Operative techniques commonly used for fissure in ano include: anal stretch, open lateral sphincterotomy, closed lateral sphincterotomy, posterior midline sphincterotomy and to a lesser extent dermal flap coverage of the fissure. Reports of direct comparisons between operative techniques for anal fissure are variable in their results. These reports are either subject to selection bias (in non-randomized studies) or observer bias (in all studies) or have inadequate numbers of patients enrolled to answer the question of efficacy. OBJECTIVES: To determine the best technique for fissure surgery. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials and MEDLINE (1965-2005) were searched. The list of cited references in all included reports and several study authors also were helpful in finding additional comparative studies. SELECTION CRITERIA: All reports in which there was a direct comparison between at least two operative techniques were reviewed and when more than one report existed for any given pair, that report was included. If crude data were not presented in the report, the authors were contacted and crude data obtained. DATA COLLECTION AND ANALYSIS: The two most commonly used end points in all reported studies were persistence of the fissure and post operative incontinence of flatus. These are the only two endpoints included in the meta-analysis. MAIN RESULTS: Twenty-four trials encompassing 3475 patients are included in this review . Anal stretch has a higher risk of fissure persistence than internal sphincterotomy and also a significantly higher risk of minor incontinence than sphincterotomy. The combined results of open versus closed partial lateral internal sphincterotomy show little difference between the two procedures both in fissure persistence and risk of incontinence. AUTHORS' CONCLUSIONS: Anal stretch and posterior midline internal sphincterotomy should probably be abandoned in the treatment of chronic anal fissure in adults. For those patients requiring surgery for anal fissure, open and closed partial lateral internal sphincterotomy appear to be equally efficacious. More data are needed to assess the effectiveness of posterior internal sphincterotomy, anterior levatorplasty, wound suture or papilla excision.