Small Bowel Motility in Ulcerative Colitics Undergoing Ileal Pouch-Anal Anastomosis

Although much clinical research has been carried out in the last 14 years to examine the postoperative function of patients undergoing ileal pouch-anal anastomosis (IPAA), little is known about the small bowel which is used to create the reservoir in this procedure. This thesis has therefore examined the preoperative small bowel motility characteristics of patients with ulcerative colitis (UC) undergoing EPAA using in vivo and in vitro techniques. The in vitro studies were compared against control subjects of whom most were undergoing elective right hemicolectomy for non-obstructing neoplasms. During part of the research project access to ileal tissue from patients with idiopathic slow transit constipation (ISTC) undergoing subtotal colectomy and ileorectal anastomosis (SC+IRA) enabled a study of this interesting subgroup of patients to be made. A review of the IPAA operation performed at Glasgow Royal Infirmary between 1988 and 1995 i.e. totally stapled restorative proctocolectomy (TSRP), was also carried out. (Abstract shortened by ProQuest.)

Ambulatory Seton Placement Followed by Fistulotomy: Efficacy and Safety for Perianal Fistula Treatment

Purpose: To evaluate the efficacy and safety of ambulatory seton placement followed by superficial fistulotomy as treatment of perianal fistula. Methods: Retrospective observational analysis of patients with cryptogenic perianal fistula aged 18-90 years, followed in a central hospital proctology consultation between 2006 and 2017. Data were obtained through clinical record's analysis. Fistula was characterized, using Parks Classification. A probe was passed through the fistula tract, followed by a seton, which remained in situ until superficial fistulotomy was possible. Results: Ninety-six patients were included (66.67% males, mean age 56 ± 15 years old). Nineteen patients (19.89%) had previous history of perianal fistula and 14 (14.58%) previous anorectal surgery. Seventy-four patients (78.72%) were submitted to fistulotomy, three (3.19%) had seton fistulotomy and one had no seton progression. Intention-to-treat and per-protocol efficacy analyses were 80.2 and 98.7%, respectively. Among the 74 patients who completed the procedure, type of fistula and time with seton were distributed as followed: 47 (63.51%) intersphincteric fistula (15 ± 31 weeks), 26 (35.14%) transsphincteric fistula (32 ± 47 weeks), one (1.35%) suprasphincteric fistula (11 weeks). Previous fistula was associated with a longer time with seton (P = 0.018). Incontinence was reported in two (2.7%) patients, who had previous perianal fistula or anorectal surgery. Two patients (2.7%) had recurrence after fistulotomy. Conclusion: Placement of seton followed by superficial fistulotomy in an ambulatory setting is a safe and effective method for simple low perianal fistula treatment. Incontinence rate may be higher in patients with previous perianal fistula or anorectal surgery.info:eu-repo/semantics/publishedVersio

Control of cytokine production from human monocytic cells by prostaglandin 15-Deoxy-Δ-12,14-prostaglandin J2

Prostaglandins have several roles, but their main function is within the inflammatory process. As part of the immune response, immune cells are stimulated by lipopolysaccharide to produce pro- and anti-inflammatory cytokines including tumour necrosis factor-alpha, interleukin-1beta and interleukin-10. These cytokines can go on to stimulate the production of prostaglandins such as prostaglandin E2, prostaglandin D2 and 15-deoxy-Δ-12,14-prostaglandin J2. 15-deoxy-Δ-12,14-prostaglandin J2, is a metabolite of prostaglandin D2.;Prostaglandins have both pro- and anti-inflammatory roles. Not much is known about the pro- and anti-inflammatory effects of 15-deoxy-Δ-12,14-prostaglandin J2. As prostaglandins like prostaglandin E2, have inhibitory effects on pro-inflammatory cytokines it is an intriguing possibility that 15-deoxy-Δ-12,14-prostaglandin J2 may also share these qualities. It is also not known what cell receptor mediates these responses or what intracellular pathway is activated.;Thus, our aim was to discover what effects that 15-deoxy-Δ-12,14 -prostaglandin J2 had on the levels of pro- and anti-inflammatory cytokines, tumour necrosis factor-alpha, interleukin-1beta and interleukin-10. As well as to understand what receptor, either the prostaglandin D2 receptors DP1 or DP2, that 15-deoxy-Δ-12,14-prostaglandin J2 binds to and if cyclic adenosine monophosphate is involved in the signalling pathway.;This was achieved by stimulating the human monocytic cell line, THP-1 cells, with lipopolysaccharide and incubated for 22 hours with prostaglandins; 15-deoxy-Δ-12,14-prostaglandin J2, prostaglandin D2 and prostaglandin E2 which were used as comparisons. DP1 and DP2 antagonists BW868C and CAY10471 respectively and the cyclic adenosine monophosphate inhibitor SQ22536. The supernatants which contained the cytokines were measured by enzyme-linked immunosorbent assay. After the incubations, the cells were removed, and cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after stimulation with lipopolysaccharide in the presence or absence of prostaglandin E2.;15-deoxy-Δ-12,14-prostaglandin J2 downregulated the levels of tumour necrosis factor-alpha by 81% and interleukin-1beta by 33% in a concentration dependent manner but had no effect on the levels of interleukin-10. As the concentration of prostaglandin E2 increased it downregulated the levels of tumour necrosis factor-alpha, interleukin-1beta and interleukin-10 by 100%, 69% and 82.6% respectively.;Surprisingly, neither of the DP antagonists had any effect on the activity of 15-deoxy-Δ-12,14-prostaglandin J2. CAY10471 (DP2), inhibited prostaglandin D2 from decreasing the level of tumour necrosis factor-alpha, but BW868C (DP1) did not have any effect. When using the cyclic adenosine monophosphate inhibitor, SQ22536, it had no effect on the levels of tumour necrosis factor-alpha, with either 15-deoxy-Δ-12,14-prostaglandin J2 or prostaglandin D2. Lipopolysaccharide and prostaglandin E2 had no effect on THP-1 cell viability confirmed by no change in the converted formazan dye.;This data indicates that 15-deoxy-Δ-12,14-prostaglandin J2 has inhibitory effects on pro-inflammatory cytokines tumour necrosis factor-alpha and interleukin -1beta but has no effect on the anti-inflammatory cytokine interleukin-10 in human monocytic cells. The data strongly suggests that as the DP antagonists BW868C and CAY10471 do not affect the function of 15-deoxy-Δ-12,14-prostaglandin J2 then neither the DP1 or DP2 receptors are involved in the anti-inflammatory effects of 15-deoxy-Δ-12,14-prostaglandin J2.;Also, as the cyclic adenosine monophosphate inhibitor SQ22536 had no effect either on the function of 15-deoxy-Δ-12,14-prostaglandin J2, this rules out that the cyclic adenosine monophosphate pathway is involved. This is inclusive of any other receptors that follow this pathway. Further work can be carried out to understand what receptor and pathway are stimulated. As 15-deoxy-Δ-12,14-prostaglandin J2 has shown to be suppressive of tumour necrosis factor-alpha and interleukin -1beta, and as it does not alter the levels of the anti-inflammatory cytokine interleukin-10, it is propitious that it may be used successfully to modulate the inflammatory process and be developed into a therapy for inflammatory conditions.Prostaglandins have several roles, but their main function is within the inflammatory process. As part of the immune response, immune cells are stimulated by lipopolysaccharide to produce pro- and anti-inflammatory cytokines including tumour necrosis factor-alpha, interleukin-1beta and interleukin-10. These cytokines can go on to stimulate the production of prostaglandins such as prostaglandin E2, prostaglandin D2 and 15-deoxy-Δ-12,14-prostaglandin J2. 15-deoxy-Δ-12,14-prostaglandin J2, is a metabolite of prostaglandin D2.;Prostaglandins have both pro- and anti-inflammatory roles. Not much is known about the pro- and anti-inflammatory effects of 15-deoxy-Δ-12,14-prostaglandin J2. As prostaglandins like prostaglandin E2, have inhibitory effects on pro-inflammatory cytokines it is an intriguing possibility that 15-deoxy-Δ-12,14-prostaglandin J2 may also share these qualities. It is also not known what cell receptor mediates these responses or what intracellular pathway is activated.;Thus, our aim was to discover what effects that 15-deoxy-Δ-12,14 -prostaglandin J2 had on the levels of pro- and anti-inflammatory cytokines, tumour necrosis factor-alpha, interleukin-1beta and interleukin-10. As well as to understand what receptor, either the prostaglandin D2 receptors DP1 or DP2, that 15-deoxy-Δ-12,14-prostaglandin J2 binds to and if cyclic adenosine monophosphate is involved in the signalling pathway.;This was achieved by stimulating the human monocytic cell line, THP-1 cells, with lipopolysaccharide and incubated for 22 hours with prostaglandins; 15-deoxy-Δ-12,14-prostaglandin J2, prostaglandin D2 and prostaglandin E2 which were used as comparisons. DP1 and DP2 antagonists BW868C and CAY10471 respectively and the cyclic adenosine monophosphate inhibitor SQ22536. The supernatants which contained the cytokines were measured by enzyme-linked immunosorbent assay. After the incubations, the cells were removed, and cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after stimulation with lipopolysaccharide in the presence or absence of prostaglandin E2.;15-deoxy-Δ-12,14-prostaglandin J2 downregulated the levels of tumour necrosis factor-alpha by 81% and interleukin-1beta by 33% in a concentration dependent manner but had no effect on the levels of interleukin-10. As the concentration of prostaglandin E2 increased it downregulated the levels of tumour necrosis factor-alpha, interleukin-1beta and interleukin-10 by 100%, 69% and 82.6% respectively.;Surprisingly, neither of the DP antagonists had any effect on the activity of 15-deoxy-Δ-12,14-prostaglandin J2. CAY10471 (DP2), inhibited prostaglandin D2 from decreasing the level of tumour necrosis factor-alpha, but BW868C (DP1) did not have any effect. When using the cyclic adenosine monophosphate inhibitor, SQ22536, it had no effect on the levels of tumour necrosis factor-alpha, with either 15-deoxy-Δ-12,14-prostaglandin J2 or prostaglandin D2. Lipopolysaccharide and prostaglandin E2 had no effect on THP-1 cell viability confirmed by no change in the converted formazan dye.;This data indicates that 15-deoxy-Δ-12,14-prostaglandin J2 has inhibitory effects on pro-inflammatory cytokines tumour necrosis factor-alpha and interleukin -1beta but has no effect on the anti-inflammatory cytokine interleukin-10 in human monocytic cells. The data strongly suggests that as the DP antagonists BW868C and CAY10471 do not affect the function of 15-deoxy-Δ-12,14-prostaglandin J2 then neither the DP1 or DP2 receptors are involved in the anti-inflammatory effects of 15-deoxy-Δ-12,14-prostaglandin J2.;Also, as the cyclic adenosine monophosphate inhibitor SQ22536 had no effect either on the function of 15-deoxy-Δ-12,14-prostaglandin J2, this rules out that the cyclic adenosine monophosphate pathway is involved. This is inclusive of any other receptors that follow this pathway. Further work can be carried out to understand what receptor and pathway are stimulated. As 15-deoxy-Δ-12,14-prostaglandin J2 has shown to be suppressive of tumour necrosis factor-alpha and interleukin -1beta, and as it does not alter the levels of the anti-inflammatory cytokine interleukin-10, it is propitious that it may be used successfully to modulate the inflammatory process and be developed into a therapy for inflammatory conditions