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Objectives To prospectively assess the efficacy and safety of Lactobacillus vaginal suppositories for the prevention of recurrent cystitis. Methods In this single-arm, open-label, phase II clinical trial, participants used vaginal suppositories containing the GAI 98322 strain of Lactobacillus crispatus for 1 year either every 2 days or three times per week. The primary end-point was the response rate, as assessed by the number of episodes of recurrent cystitis during the year of administration. The secondary end-points were the response rate, as assessed by episodes of recurrent cystitis during the 1 year after completion of the administration period; the total number of episodes of recurrent cystitis before, during and after administration; adverse events; and changes in urine bacteria and the vaginal microbiome. Results A total of 28 women were enrolled, and 21 completed the study. A total of 18 patients achieved an effective response (86%) during administration. The suppressive effects of Lactobacillus vaginal suppositories on episodes of cystitis continued up to 1 year after the last suppository was administered. There was a significant reduction in the mean number of episodes of cystitis, both during and after administration of Lactobacillus vaginal suppositories. No treatment-related adverse events were observed. Amplicon sequencing analysis of the vaginal microbiome showed that Lactobacillus species colonized the vagina during the periods when episodes of cystitis were absent. Conclusions Vaginal suppositories containing the GAI 98322 strain of Lactobacillus crispatus effectively prevent episodes of recurrent cystitis, both during administration and for at least 1 year after administration.

AIM Gestational hypertension is a common disorder of pregnancy. This study aims to evaluate the effect of labor induction with dinoprostone vaginal suppositories (Propess) on pregnancy outcomes in pregnant women with gestational hypertension. METHODS The retrospective study included 375 patients with gestational hypertension. All patients were included into three groups according to the characteristics at admission. Women who had initiated labor spontaneously at admission were enrolled in Spontaneous labor group. According to Bishop score, other patients underwent labor induction with Propess or oxytocin were enrolled in Propess group or Oxytocin group. Demographic information and perinatal outcome data were collected. RESULTS The vaginal delivery rate of the women with gestational hypertension was respectively 93.5% (Spontaneous labor group), 77.0% (Propess group), and 52.5% (Oxytocin group) in three groups with significant difference (P

We report a case of long-standing inexplicable perianal ulcers. After exclusion of an inflammatory, infectious or neoplastic origin, a thorough personal history revealed that for many years the patient had been using analgesic suppositories containing indomethacin, caffeine, and prochlorperazine dimaleate, four to five times a week, for migraine. On stopping the suppositories, there was complete healing within 12 weeks. We hypothesize that vasoconstriction and vascular damage were the pathogenetic mechanisms behind the perianal ulcers.

In this issue of the Journal, Professor Elmunzer provides an outstanding overview of the variable methods of prevention of post-ERCP pancreatitis (PEP) (1). We all recognize the importance of this topic given its morbidity for our patients. His review succinctly summarizes a wealth of both old and new data underscoring previously identified risk factors for PEP which have stood the test of time. In addition, newer interventions are appraised and placed in an appropriate context. This article is protected by copyright. All rights reserved.

Aim 5-Aminosalicylic acid is the first-line drug for mild to moderate ulcerative colitis (UC). The most commonly used 5-aminosalicylic acid is mesalamine. Several systematic reviews have demonstrated that mesalamine is effective in inducing and maintaining remission. Efficacy, safety and adherence to once daily (OD) and multiple daily (MD) dosing of mesalamine for the induction and maintenance of remission in mild to moderate UC were systematically reviewed and compared. Method PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched from inception to November 2014. Only randomized controlled trials were considered eligible. STATA software (version 12.0) was used to calculate the pooled risk ratios with 95% confidence interval. Results Seventeen randomized studies containing 5439 patients were identified. No significant differences were noted in comparisons between OD and MD dosing for maintenance and induction of remission. No significant differences were noted in rates of medication adherence or adverse events between OD and MD dosing. With regard to mesalamine suppository, no significant differences were noted for comparisons between dosing regimens and adverse events for induction of remission. Conclusion OD dose of mesalamine is as effective and safe as MD doses for the induction and maintenance treatment of mild to moderate UC. OD mesalamine given as a suppository can attain the same effect and safety as MD mesalamine in inducing remission of mild to moderate ulcerative colitis.

AIM A well-documented, clinically proven per rectum treatment for childhood constipation is needed. This phase two clinical trial evaluated the efficacy of suppositories containing free fatty acids (FFA) compared with Klyx docusate sodium and sorbitol enemas. METHODS A randomised, controlled, single-blind study was undertaken on 77 children aged between one and 17 who presented to an emergency department in Iceland and were diagnosed with constipation. In stage one, 23 patients were randomised to receive lower dose FFA suppositories or Klyx (n = 33). In stage two, 21 different patients were randomised to receive higher dose suppositories and compared with the same Klyx control subjects. RESULTS The suppositories were effective at bowel emptying in 39% of the group who received the lower FFA doses and 81% of the group receiving higher doses, compared with 88% in the Klyx control group. Symptom relief was obtained in 30% of the group receiving the lower doses and 71% of the group receiving the higher doses, compared with 73% in the control group. CONCLUSION The higher dose FFA suppositories were as effective as the Klyx enemas with regard to bowel emptying and symptom relief and might provide an important and less invasive alternative for childhood constipation.

Background Antipsychotic-related constipation is a common and serious adverse effect, especially for people taking clozapine. Clozapine has been shown to impede gastrointestinal motility, leading to constipation, and has been reported in up to 60% of patients receiving clozapine. In rare cases, complications can be fatal. Appropriate laxatives should be prescribed to treat constipation in people taking antipsychotics, but there is a lack of guidance on the comparative effectiveness and harms of different agents in this population. An understanding of the effectiveness and safety of treatment for antipsychotic-related constipation is important for clinicians and patients alike. Objectives To evaluate the effectiveness and safety of pharmacologic treatment (versus placebo or compared against another treatment) for antipsychotic-related constipation (defined as constipated patients of any age, who are treated with antipsychotics, regardless of dose, in which constipation is considered to be an antipsychotic-related side effect). Search methods We searched the Cochrane Schizophrenia Group’s Trials Register (15 June 2015), which is based on regular searches of MEDLINE, Embase, CINAHL, BIOSIS, AMED, PubMed, PsycINFO, and registries of clinical trials, grey literature, and conference proceedings. There are no language, date, document type, or publication status limitations for inclusion of records in this register. We also handsearched bibliographies and contacted relevant authors for additional information. Selection criteria We included all published and unpublished randomised controlled trials (RCTs) investigating the efficacy of pharmacological treatments in patients with antipsychotic-related constipation. Pharmacological treatments included laxatives and other medicines that could reasonably be used to combat constipation in this population (e.g. anticholinergic agents, like bethanecol). Data collection and analysis Two review authors independently extracted data from all included studies and assessed trials for risk of bias. A third author reviewed 20% of trials. We analysed dichotomous data using relative risks (RR) and the 95% confidence intervals (CI). We assessed risk of bias for included studies and used GRADE to create a 'Summary of findings' table. We discussed any disagreement, documented decisions, and attempted to contact study authors when necessary. Main results We identified two relevant Chinese studies (N = 480) that contributed data to this review. Both studies were over ten years old and poorly reported, lacking descriptions of contemporary CONSORT reporting prerequisites, such as sequence generation, allocation concealment, blinding, participant flow, how the sample size was determined, or how outcomes were measured. The studies also did not report trial registration, pre-specified protocols, consent processes, ethical review, or funding source. We were unsuccessful in making contact with the authors to clarify the missing details. We classified both studies as having an overall high risk of bias. One study compared glycerol suppository with the traditional Chinese medicine (TCM) approaches of tuina massage and acupuncture. Compared to tuina massage, glycerol laxative was less effective in relieving constipation at both two days after treatment (1 RCT; N = 120; RR 2.88, 95% CI 1.89 to 4.39; very low-quality evidence), and three days (1 RCT; N = 120; RR 4.80, CI 1.96 to 11.74, very low-quality evidence). Favourable results were also seen for acupuncture at two days (1 RCT; N = 120; RR 3.50; 95% CI 2.18 to 5.62; very low-quality evidence), and at three days (1 RCT; N = 120; RR 8.00, 95% CI 2.54 to 25.16; very low-quality evidence). The other study compared mannitol, an osmotic laxative, with rhubarb soda or phenolphthalein. Mannitol was more effective than rhubarb soda or phenolphthalein in trelieving constipation within 24 hours of treatment (1 RCT; N = 240; RR 0.07; 95% CI 0.02 to 0.27, very low-quality evidence). No data were reported for our other important outcomes: need for rescue medication, bowel obstruction (a complication of antipsychotic-related constipation), quality of life, adverse events, leaving the study early, and economic costs. Authors' conclusions We had hoped to find clinically useful evidence appraising the relative merits of the interventions routinely used to manage antipsychotic-related constipation, a common and potentially serious adverse effect of the use of these drugs. The results were disappointing. There were no data comparing the common pharmacological interventions for constipation, such as lactulose, polyethylene glycol, stool softeners, lubricant laxatives, or of novel treatments such as linaclotide. Data available were very poor quality and the trials had a high risk of bias. Data from these biased studies suggested that mannitol, an osmotic laxative, was more effective than rhubarb soda and phenolphthalein in relieving constipation, and a two-week course of glycerol suppositories was less effective than the TCM approaches of tuina massage and acupuncture. Overall, there is insufficient trial-based evidence to assess the effectiveness and safety of pharmacological interventions for treating antipsychotic-related constipation, due to limited, poor quality data (few studies with high risk of bias and no meta-analyses). The methodological limitations in the included studies were obvious, and any conclusions based on their results should be made with caution. Methodologically rigorous RCTs evaluating interventions for treating antipsychotic-related constipation are needed.

Aims This study aimed to assess the dose and volume effects of suppository preparations and safety of NRL001 (one of four possible stereoisomers of methoxamine hydrochloride) on anal sphincter tone using rectal suppositories in healthy adult volunteers. Methods This was a Phase I, single-centre, randomised, double-blind, three-way crossover study during which subjects received three single doses of 1 g rectal suppositories (containing 5 or 10 mg NRL001 or matching placebo) or 2 g rectal suppositories (containing 10 or 15 mg NRL001 or matching placebo) on three separate dosing days. The outcome measures were mean anal resting pressure (MARP) variables (monitored continuously for 20–30 min before and up to 6 h after dosing), pharmacokinetics (PK) and safety assessments. Results Twenty-six subjects were dosed with study medication. Two subjects were withdrawn prematurely and were not included in the main analysis. There was a dose-dependent increase in anal sphincter tone (MARP) when comparing the 5 and 10 mg doses of NRL001; however, the 15 mg dose did not have a significantly greater effect than the 10 mg dose. Suppository size (1 or 2 g) did not appear to have an effect on sphincter tone. There was no evidence against dose proportionality for the PK variables, but the mean maximum plasma concentration (Cmax) for the 1 g suppository group was higher than for the 2 g group. Twenty-one adverse events were reported in 8 (30.8%) subjects. A dose dependent decrease in heart rate was noted; however, there were no adverse events reported that were related to this reduction in heart rate. Conclusions The increase in anal sphincter tone supports the potential therapeutic use of NRL001 in treating faecal incontinence, with further studies in patients required. NRL001 was well tolerated in single doses of up to 15 mg.

Aims The 1R,2S stereoisomer of methoxamine hydrochloride, NRL001, is a highly selective α1-adrenoceptor agonist being developed for the local treatment of non-structural faecal incontinence caused by weak internal anal sphincter tone. This study investigated the steady state pharmacokinetics (PK) and safety of 2 g rectal suppositories containing NRL001 in different strengths (7.5, 10, 12.5 or 15 mg). Methods Healthy volunteers aged 18–45 years received 14 daily doses of NRL001 2 g suppositories or matching placebo. In each dose group nine participants received NRL001 and three received placebo. Blood samples to determine NRL001 concentrations were taken on Days 1, 7 and 14. Cardiovascular parameters were collected via electrocardiograms, Holter monitoring (three lead Holter monitor) and vital signs. Results Forty-eight volunteers were enrolled; 43 completed the study and were included in the PK analysis population. AUC and Cmax broadly increased with increasing dose, Tmax generally occurred between 4.0 and 5.0 h. Although the data did not appear strongly dose proportional, dose proportionality analysis did not provide evidence against dose proportionality as the log(dose) coefficients were not significantly

Curcumin interacts with a large number of extra- and intracellular targets in a biphasic dose-dependent manner. It controls inflammation, oxidative stress, cell survival, cell secretion, homeostasis, and proliferation. Its mechanisms of action are generally directed toward cells that exhibit disordered physiology or blatant mutation-based abnormal states. Optimizing preventative or therapeutic applications require delivering appropriate quantities of curcumin to lesioned cellular targets. Since diseased conditions anatomically are located from topical to systemic sites, efficient application of curcumin requires specific lesion-oriented delivery methods, representatives of which are here reviewed. © 2013 BioFactors, 39(1):21–26, 2013

BACKGROUND: Pouchitis occurs in approximately 50% of patients following ileal pouch‐anal anastomosis (IPAA) for chronic ulcerative colitis (UC). OBJECTIVES: The primary objective was to determine the efficacy and safety of medical therapies for prevention or treatment of acute or chronic pouchitis. SEARCH METHODS: We searched MEDLINE, Embase and CENTRAL from inception to 25 July 2018. We also searched references, trials registers, and conference proceedings. SELECTION CRITERIA: Randomized controlled trials of prevention or treatment of acute or chronic pouchitis in adults who underwent IPAA for UC were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently screened studies for eligibility, extracted data and assessed the risk of bias. The certainty of the evidence was evaluated using GRADE. The primary outcome was clinical improvement or remission in participants with acute or chronic pouchitis, or the proportion of participants with no episodes of pouchitis after IPAA. Adverse events (AEs) was a secondary outcome. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for each dichotomous outcome. MAIN RESULTS: Fifteen studies (547 participants) were included. Four studies assessed treatment of acute pouchitis. Five studies assessed treatment of chronic pouchitis. Six studies assessed prevention of pouchitis. Three studies were low risk of bias. Three studies were high risk of bias and the other studies were unclear. Acute pouchitis: All ciprofloxacin participants (7/7) achieved remission at two weeks compared to 33% (3/9) of metronidazole participants (RR 2.68, 95% CI 1.13 to 6.35, very low certainty evidence). No ciprofloxacin participants (0/7) had an AE compared to 33% (3/9) of metronidazole participants (RR 0.18, 95% CI 0.01 to 2.98; very low certainty evidence). AEs included vomiting, dysgeusia or transient peripheral neuropathy. Forty‐three per cent (6/14) of metronidazole participants achieved remission at 6 weeks compared to 50% (6/12) of budesonide enema participants (RR 0.86, 95% CI 0.37 to 1.96, very low certainty evidence). Fifty per cent (7/14) of metronidazole participants improved clinically at 6 weeks compared to 58% (7/12) of budesonide enema participants (RR 0.86, 95% CI 0.42 to 1.74, very low certainty evidence). Fifty‐seven per cent (8/14) of metronidazole participants had an AE compared to 25% (3/12) of budesonide enema participants (RR 2.29, 95% CI 0.78 to 6.73, very low certainty evidence). AEs included anorexia, nausea, headache, asthenia, metallic taste, vomiting, paraesthesia, and depression. Twenty‐five per cent (2/8) of rifaximin participants achieved remission at 4 weeks compared to 0% (0/10) of placebo participants (RR 6.11, 95% CI 0.33 to 111.71, very low certainty evidence). Thirty‐eight per cent (3/8) of rifaximin participants improved clinically at 4 weeks compared to 30% (3/10) of placebo participants (RR 1.25, 95% CI 0.34 to 4.60, very low certainty evidence). Seventy‐five per cent (6/8) of rifaximin participants had an AE compared to 50% (5/10) of placebo participants (RR 1.50, 95% CI 0.72 to 3.14, very low certainty evidence). AEs included diarrhea, flatulence, nausea, proctalgia, vomiting, thirst, candida, upper respiratory tract infection, increased hepatic enzyme, and cluster headache. Ten per cent (1/10) of Lactobacillus GG participants improved clinically at 12 weeks compared to 0% (0/10) of placebo participants (RR 3.00, 95% CI 0.14 to 65.90, very low certainty evidence). Chronic pouchitis: Eighty‐five per cent (34/40) of De Simone Formulation (a probiotic formulation) participants maintained remission at 9 to 12 months compared to 3% (1/36) of placebo participants (RR 20.24, 95% CI 4.28 to 95.81, 2 studies; low certainty evidence). Two per cent (1/40) of De Simone Formulation participants had an AE compared to 0% (0/36) of placebo participants (RR 2.43, 95% CI 0.11 to 55.89; low certainty evidence). AEs included abdominal cramps, vomiting and diarrhea. Fifty per cent (3/6) of adalimumab patients achieved clinical improvement at 4 weeks compared to 43% (3/7) of placebo participants (RR, 1.17, 95% CI 0.36 to 3.76, low certainty evidence). Sixty per cent (6/10) of glutamine participants maintained remission at 3 weeks compared to 33% (3/9) of butyrate participants (RR 1.80, 95% CI 0.63 to 5.16, very low certainty evidence). Forty‐five per cent (9/20) of patients treated with bismuth carbomer foam enema improved clinically at 3 weeks compared to 45% (9/20) of placebo participants (RR 1.00, 95% CI 0.50 to 1.98, very low certainty evidence). Twenty‐five per cent (5/20) of participants in the bismuth carbomer foam enema group had an AE compared to 35% (7/20) of placebo participants (RR 0.71, 95% CI 0.27 to 1.88, very low certainty evidence). Adverse events included diarrhea, worsening symptoms, cramping, sinusitis, and abdominal pain. Prevention: At 12 months, 90% (18/20) of De Simone Formulation participants had no episodes of acute pouchitis compared to 60% (12/20) of placebo participants (RR 1.50, 95% CI 1.02 to 2.21, low certainty evidence). Another study found 100% (16/16) of De Simone Formulation participants had no episodes of acute pouchitis at 12 months compared to 92% (11/12) of the no treatment control group (RR 1.10, 95% 0.89 to 1.36, very low certainty evidence). Eighty‐six per cent (6/7) of Bifidobacterium longum participants had no episodes of acute pouchitis at 6 months compared to 60% (3/5) of placebo participants (RR 1.43, 95% CI 0.66 to 3.11, very low certainty evidence). Eleven per cent (1/9) of Clostridium butyricum MIYAIRI participants had no episodes of acute pouchitis at 24 months compared to 50% (4/8) of placebo participants (RR 0.22, 95% CI 0.03 to 1.60, very low certainty evidence). Forty‐six per cent (43/94) of allopurinol participants had no episodes of pouchitis at 24 months compared to 43% (39/90) of placebo participants (RR 1.06, 95% CI 0.76 to 1.46; low certainty evidence). Eighty‐one per cent (21/26) of tinidazole participants had no episodes of pouchitis over 12 months compared to 58% (7/12) of placebo participants (RR 1.38, 95% CI 0.83 to 2.31, very low certainty evidence). AUTHORS' CONCLUSIONS: The effects of antibiotics, probiotics and other interventions for treating and preventing pouchitis are uncertain. Well designed, adequately powered studies are needed to determine the optimal therapy for the treatment and prevention of pouchitis.

A new analog of prostaglandin E1 (PGE1) was administered vaginally to women with (n=20) and without (n=29) laminaria tents and metreurynter for therapeutic abortion during the 2nd trimester. All patients aborted successfully. The abortion time was short, bleeding was minimal, and there was little difference between patients treated with 16 DM-PGE1 alone and those treated with 16 DM-PGE1, laminaria tents, and metreurynter. However, amounts of 16 DM-PGE1 required for abortion were significantly greater in patients treated with 16 DM-PGE1 alone. Occurrences of side effects increased with increased amounts of 16 DM-PGE1 administered. Therefore, vaginal administration of that in combination with the use of laminaria tents and metreurynter successfully induced abortion in women during the midtrimester with minimal side effects, and was considered to be the best method presently available for midtrimester therapeutic abortion.

Serum concentrations of diazepam and N-desmethyldiazepam were measured in six adult patients following administration of 10 mg diazepam in solution by the rectal, intravenous, and intramuscular routes. Maximum serum concentrations of 121--200 ng/ml were recorded from 10 to 20 min. after the rectal instillation, whereas following intramuscular injection the levels rose slowly and irregularly, reaching a maximum (62--186 ng/ml) in 1 to 24 hours. The bioavailability of diazepam given by rectal instillation was found to be 50 +/- 17 per cent (mean +/- S. D.) as compared with the intravenous administration. The possible reasons for the low bioavailability are discussed. It is concluded that administration by rectal tube provides a useful alternative to the tablets (and intramuscular injections) when a rapid onset of effect of the drug is wanted, and when intravenous administration is not applicable or practical.

A simple gas chromatographic analytical method for determining diazepam and its major metabolites in the blood, urine, and muscle homogenate is described. Its applicability is illustrated by bioavailability studies, on man and on animals. The human studies revealed equivalence between two marketed brands of diazepam tablets and a slight difference between two brands of suppositories. The animal experiments showed agreement of in vivo properties of two different formulations of a diazepam injection fluid.

The pharmacokinetics of indomethacin was studied after intravenous and intramuscular injection of 50 mg and administration of rectal solution and suppositories of 100 mg to 8 volunteers. Peak plasma concentrations of indomethacin occurred 20 min. after administration of the rectal solution (3.7 micrograms X ml-1), 40 min. after intramuscular injection (2.7 micrograms X ml-1), and 60 min. after suppositories (3.7 micrograms X ml-1). The bioavailability after the two rectal forms was found to be almost the same, about 80%. After intramuscular injection the bioavailability was calculated to be complete. These results suggest that indomethacin administered as a rectal solution or as intramuscular injection may be an alternative to intravenous administration when an early plasma peak of the drug is required.

The fate of emepronium (cetiprin®) in the dog has been studied following different routes of administration. The drug is rather extensively metabolized following both intravenous, oral and rectal administration. At least two metabolites are formed. Following intravenous injection twice as much radioactivity is found in the faeces as in the urine, about half in the form of the unchanged drug. This means that there is probably an extensive enterohepatic circulation of the drug. In four dogs 0.6, 0.8, 1.1 and 1.6 % of the dose was excreted unchanged in the urine within 24 hours following oral administration of 20 mg/kg. It is concluded from experiments with the radioactive compound that from 2 to 10 % of the dose is absorbed if metabolism and biliary excretion are taken into account. Plasma concentrations of emepronium in the nanogram range can be determined by gas chromatography of the oxidation product, ben-zophenone. A plasma concentration of about 20 μ/ml is lethal to both rats and dogs and the threshold concentration for an effect on the heart rate in the dog is about 100 ng/ml.

The common practice is to use 162 mg of aspirin orally in the emergency department (ED) for patients presenting with myocardial infarction. If the patient cannot take aspirin orally in the authors' facility, then 600 mg of aspirin is given rectally. However, no strong evidence exists as to whether the oral and rectal doses provide equivalent risk protection. The authors hypothesized that the salicylic acid levels for orally and rectally administered aspirin will not be similar, because of the different dosages used and the different routes of administration.The study sample consisted of healthy, nonpregnant, adult volunteers without active illness, who did not take any medication regularly. Each subject served as his or her own control to account for any confounding factors. The study was conducted on 2 days, separated by a 1-week washout period. On the first day, 162 mg of oral aspirin was chewed and swallowed. Salicylic acid levels were obtained at baseline (i.e., before taking the aspirin) and then 30, 60, and 90 minutes after dosing. The 600-mg aspirin suppository was self-administered 1 week later with a sample for laboratory measures again drawn at baseline and then 30, 60, and 90 minutes after dosing.Twenty-four subjects completed the study. The rectal suppository provided significantly more salicylic acid into the blood than the oral tablets over 90 minutes (p0.001). No statistical difference was noted between oral and rectal administration from baseline to 30 minutes (p0.05). However, mean salicylic acid levels from the rectal suppository were statistically higher than from the oral tablets from 30 to 60 minutes (p0.001) and from 60 to 90 minutes (p = 0.002). More than 60% of the subjects had an increasing salicylic acid level response over time to the rectal suppository. The salicylic acid level response to the oral administration was more evenly divided between those subjects whose salicylic acid levels peaked quickly and then fell or held steady (33%), those whose salicylic acid levels increased over time (29%), and those whose salicylic acid levels were measureable only after 60 minutes (25%). Although not statistically significant, these differences in group distributions for the type of salicylic acid level response between oral and rectal doses suggested the possibility of a rectal advantage.Whether the higher salicylic acid levels and faster absorption of the rectal aspirin translate into better clinical outcomes is unknown and cannot be concluded from our study. Previous evidence, however, has shown that 162 mg of aspirin chewed and swallowed provided lower mortality in patients presenting with myocardial infarction. Our results suggested the rectal administration of a 600-mg suppository provides sufficient levels of salicylic acid within 90 minutes to meet or exceed that of oral aspirin.

Background and Aims: Acute pancreatitis following endoscopic retrograde cholangiog- raphy presents a unique opportunity for prophylaxis and early modification of the disease process because the initial triggering event is temporally well defined and takes place in the hospital. We report a prospective, single-center, randomized, double-blind controlled trial to determine if rectal diclofenac reduces the incidence of pancreatitis following cholangiopancreatography. Methods: Entry to the trial was restricted to patients who underwent endoscopic retro- grade pancreatography. Immediately after endoscopy, patients were given a suppository containing either 100 mg diclofenac or placebo. Estimation of serum amylase level and clinical evaluation were performed in all patients. Results: One hundred patients entered the trial, and 50 received rectal diclofenac. Fifteen patients developed pancreatitis (15%), of whom two received rectal diclofenac and 13 received placebo (P < 0.01). Conclusions: This trial shows that rectal diclofenac given immediately after endoscopic retrograde cholangiopancreatography can reduce the incidence of acute pancreatitis.

Suppositories containing 300 mg 5-aminosalicylic acid (1.96 mmol) or 425 mg acetyl-5-aminosalicylic acid (1.96 mmol) were used in 40 patients with idiopathic proctitis to determine the efficacy of acetyl-5-aminosalicylic acid in treating this bowel inflammation. Each patient was treated with 5-aminosalicylic acid or acetyl-5-aminosalicylic acid suppositories twice daily for 4 weeks in a double-blind trial. Four patients were included twice in the trial. The second time they were treated with the alternative regimen. Six patients in the acetyl-5-aminosalicylic acid group did not complete the trial, four of them because of diarrhoea. Complete clinical remission with normal rectal mucosa on sigmoidoscopy was achieved in 10 out of 18 patients on 5-aminosalicylic acid and in only two out of 15 in the acetyl-5-aminosalicylic acid group (P = 0.03). A favourable histological improvement was demonstrated with 5-aminosalicylic acid suppositories, but the difference with acetyl-5-aminosalicylic acid was not significant (P = 0.059). Three of the four patients who received both drugs recovered with 5-aminosalicylic acid; in none of them was acetyl-5-aminosalicylic acid effective. The results from this study and from previous investigations show that acetyl-5-aminosalicylic acid is not superior to placebo.

An Eudragit-L coated oral 5-aminosalicylic acid (5-ASA; mesalazine) product (Mesasal), has been formulated to deliver 5-ASA to the distal small intestine and colon for the treatment of inflammatory bowel disease. The purpose of this study was to compare the pharmacokinetic profile of this product to sulphasalazine (SASP; Salazopyrin) and to assess the pharmacokinetics of a suppository 5-ASA dosage form. Twelve healthy volunteers randomly received four single doses of 5-ASA delivering formulations not less than 1 week apart. (a) Mesasal tablets, 2 x 250 mg, fasting; (b) Mesasal tablets, 2 x 250 mg, fed; (c) Salazopyrin tablets, 3 x 500 mg (corresponding to 576 mg 5-ASA), fasting; and (d) Mesasal suppository, 1 x 500 mg, fasting. Plasma 5-ASA and acetyl-5-ASA (Ac-5-ASA) concentrations were followed for 48 h and urine and faecal concentrations for 72 h. Mesasal tablets (fasting) produced a greater area under the concentration-time curve (AUC), peak and time to peak for both plasma 5-ASA and Ac-5-ASA than Salazopyrin. Median urinary recovery values were 21.7% for Salazopyrin and 35.5% for Mesasal (fasting) (P less than 0.01). This means that the systemic absorption was higher after Mesasal than after Salazopyrin. The total faecal recovery values were 38.3 and 26.5%, respectively (NS). Except for a delay of 1.5-.3 h in the time to peak of 5-ASA and Ac-5-ASA plasma levels, the pharmacokinetics of Mesasal tablets were essentially the same in fasting or fed subjects. Suppository administration of 5-ASA resulted in a low median urinary recovery of 10.8%.

Background. The purpose of this study was to examine whether EP4 as prostaglandin (PG) E2 receptor is involved in lipopolysaccharide (LPS)-induced cervical ripening. Methods. New Zealand White non-pregnant rabbits were randomly allocated to 4 equal groups and treated with vaginal suppositories containing LPS with various concentrations of EP4-selective antagonist once daily for 3 days, and then sacrificed for analysis. Analysis was performed in order to examine the inhibitory effect of EP4 antagonist on LPS-induced cervical ripening. The expression of EP4 in a cervix treated with LPS was examined immunohistochemically. The percent of cervical extensibility in the segment of cervix as the tensile strength was determined with 5.8 g of constant perpendicular stretching. The ripening area of the cervix with edematous changes in H&E sections was calculated by a microscopic system with a computer-assisted digital analyser. Type-1 collagenase activity was determined in cervical tissue using FITC-labelled type-1 collagen. Results. Immunohistochemical study shows the positive staining of EP4 at the interstitial cells in the cervix treated with LPS. The extensibility, cervical edematous area and type-1 collagenase activity are significantly reduced in the cervix treated with LPS in the presence of EP4 antagonist compared with that treated with LPS alone. Conclusions. These data implicates the EP4 as the PGE2 receptor involved in LPS-induced cervical ripening.

Background Feeding intolerance is a common clinical problem among preterm infants. It may be an early sign of necrotising enterocolitis, sepsis or other serious gastrointestinal conditions, or it may result from gut immaturity with delayed passage of meconium. Glycerin laxatives stimulate passage of meconium by acting as an osmotic dehydrating agent and increasing osmotic pressure in the gut; they stimulate rectal contraction, potentially reducing the incidence of feeding intolerance. Objectives To assess the effectiveness and safety of glycerin laxatives (enemas/suppositories) for prevention or treatment of feeding intolerance in very low birth weight (VLBW) infants. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 4), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We restricted our search to all randomised controlled trials and applied no language restrictions. We searched the references of identified studies and reviews on this topic and handsearched for additional articles. We searched the database maintained by the US National Institutes of Health (www.clinicaltrials.gov) and European trial registries to identify ongoing trials. Selection criteria We considered only randomised or quasi-randomised controlled trials that enrolled preterm infants < 32 weeks' gestational age (GA) and/or < 1500 g birth weight. We included trials if they administered glycerin laxatives and measured at least one prespecified clinical outcome. Data collection and analysis We used standard methods of The Cochrane Collaboration and its Neonatal Group to assess methodological quality of trials, to collect data and to perform analyses. Main results We identified three trials that evaluated use of prophylactic glycerin laxatives in preterm infants. We identified no trials that evaluated therapeutic use of glycerin laxatives for feeding intolerance. Our review showed that prophylactic administration of glycerin laxatives did not reduce the time required to achieve full enteral feeds and did not influence secondary outcomes, including duration of hospital stay, mortality and weight at discharge. Prophylactic administration of glycerin laxatives resulted in failure of fewer infants to pass stool over the first 48 hours. Included trials reported no adverse events. Authors' conclusions Our review of available evidence for glycerin laxatives does not support the routine use of prophylactic glycerin laxatives in clinical practice. Additional studies are needed to confirm or refute the effectiveness and safety of glycerin laxatives for prevention or treatment of feeding intolerance in VLBW infants.

Summary Background The use of healthcare resources for the management of constipation is not well-known. Aim To analyse healthcare seeking for constipation, defined by three different criteria, and its related factors and to assess the frequency of use of laxatives, suppositories and enemas for the treatment of constipation. Methods A cross-sectional study in the general community. A questionnaire comprising 21-items was developed and delivered by mail to a random sample of 506 subjects aged 18–65 years, and belonging to a Spanish population. Results Seeking of health care was high in the sample (16%) and was similar for all definitions of constipation (over 40% of constipated subjects). It was associated with female gender, a higher educational level and two symptoms, such as prolonged defecation and abdominal pain. A 14% of the sample used laxatives, and about a 25% of constipated subjects used laxatives at least once a week. Utilization was more frequent in women, with no differences by age group. Conclusions Chronic constipation is a problem that causes an important consumption of resources in our setting, derived from laxative use and the seeking of medical help to combat the problem. The use of these resources is higher in women.

The liver is the major organ for the metabolism of homocysteine (Hcy) and production of insulin-like growth factor 1 (IGF-1). Hcy metabolism and IGF-1 synthesis may be impaired in chronic liver diseases. The study investigated the regulatory effect of a Chinese herbal suppository, Vitalliver, on Hcy and IGF-1, as well as their relationship in patients with hepatitis B infection. Forty patients with chronic hepatitis B virus (HBV) infection without cirrhosis, 25 males and 15 females, were observed for changes in Hcy and IGF-1 after the administration of Vitalliver (one nightly) for a period of 3 months. Serum levels of Hcy, IGF-1 and IGFBP-3 were measured at baseline, and at 1 month and 3 months after treatment. Vitalliver reduced Hcy levels significantly (p = 0.001) from 9.7 +/- 2.8 to 9.0 +/- 2.1 micromol/L after treatment of 3 months. Furthermore, the IGF-1 levels increased significantly (p < 0.001) from 170.2 +/- 81.8 to 212.8 +/- 80.9 ng/mL at 1 month and 187.5 +/- 72.3 ng/mL at 3 months (p = 0.001) after treatment. In conclusion, it is speculated Vitalliver may have a self-regulatory effect on the release of IGF-1 in HBV patients without liver cirrhosis.

Objective To evaluate rectal diclofenac in the relief of perineal pain after trauma during childbirth. Design A randomised, double-blind trial. Setting Delivery Suite, Women's and Children's Hospital, South Australia. Population Women with a second-degree (or greater) perineal tear or episiotomy. Methods Women were randomly allocated to either diclofenac or placebo suppositories (Anusol), using a computer-generated randomisation schedule with stratification for parity and mode of birth. Treatment packs contained two × 100 mg diclofenac or two placebo suppositories, the first being inserted when suturing was complete, and the second 12–24 hours after birth. Women were asked to complete questionnaires at 24 and 48 hours after birth relating to their degree of perineal pain using the validated Short Form McGill Pain Questionnaire. Main outcome measures Pain scores at 24 and 48 hours after birth. Results A total of 133 women were recruited, with 67 randomised to diclofenac suppositories and 66 to placebo. Women in the diclofenac group were significantly less likely to experience pain at 24 hours while walking (RR 0.8; 95% CI 0.6 to 1.0), sitting (RR 0.8; 95% CI 0.6 to 1.0), passing urine (RR 0.6; 95% CI 0.4 to 1.0) and on opening their bowels (RR 0.6; 95% CI 0.2 to 0.9) compared with those women who received placebo. These differences were not sustained 48 hours after birth. Conclusions The use of rectal non-steroidal anti-inflammatory drug suppositories is a simple, effective and safe method of reducing the pain experienced by women following perineal trauma within the first 24 hours after childbirth.

Objective.—To compare the efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine suppositories with sumatriptan suppositories in the treatment of 2 consecutive migraine attacks of moderate or severe intensity in a multicenter, randomized, crossover study. Background.—A fixed combination of indomethacin, prochlorperazine, and caffeine is the most commonly used drug for the acute treatment of migraine in Italy. No studies have been published comparing the efficacy of this combination with sumatriptan, the most widely prescribed of the triptans. Methods.—One hundred twelve patients with migraine with or without aura according to the diagnostic criteria of the International Headache Society were randomized to treat 2 migraine attacks with a fixed combination of indomethacin, prochlorperazine, and caffeine and 2 migraine attacks with sumatriptan. Both drugs were rectally administered in a single dose for each attack. Patients were asked to take study medication as soon as possible at the onset of a headache. Results.—Of the 112 patients, 88 were compliant to the protocol. More attacks became pain-free at 2 hours postdose (primary end point) on the combination than on sumatriptan (49% versus 34%; P

Objectives: To compare the outcome of induction of labor with prostaglandin E2 vaginal tablets between lower parity (parity 1–5) and grandmultiparous (parity >5) patients with a history of one previous lower segment cesarean section. Methods: A prospective study of 113 patients conducted at King Faisal Military Hospital, Khamis Mushayt, Saudi Arabia during a 5-year period spanning January1995 to December 1999. Results: There were no statistically significant differences in the two groups regarding mean maternal age, dose of prostaglandin used, gestation at delivery, mean birth weight, P >0.05. Syntocinon augmentation was used in 16 (21.9%) of the lower parity patients compared with 8 (20.0%) in the grandmultiparas but this was not statistically significant, ( P =0.677). However, there was a statistically significant difference in the cesarean section rate between the two groups, P =0.019. Although no cases of uterine hyperstimulation were recorded, there was one rupture of the uterus in each of the two groups of patients; 1.36% and 2.5%, respectively, but this was not statistically significant, P =1.000. Conclusions: The complications of induction of labor with prostaglandin E2 vaginal tablets in grandmultiparous patients with previous cesarean section were similar to those with lower parity but the cesarean section rate was significantly higher. However, larger studies are needed for validation.

The aim of this study was to evaluate the prevalence and severity of children's pain at home following (adeno)tonsillectomies. The subjects were parents of 161 children (86 boys, 75 girls) undergoing myringotomies, adenoidectomies and (adeno)tonsillectomies. The mean age of the children was 5.5 years (SD=2.4; range 1-14). Parents were asked to assess the child's average pain on the day of operation and 7 days after the operation, using a 100 mm Visual Analogue Scale (VAS). Parents from (adeno)tonsillectomy patients were also interviewed by phone on day 7.The mean VAS pain intensity scores by period (day of operation until 7th day after operation) differed between the myringotomy (3.2), adenoidectomy (10.6), and (adeno)tonsillectomy (22.1) group (F(2,133)=31.65; p

Objective To determine the prevalence of bacterial vaginosis in women undergoing first trimester suction termination of pregnancy and to evaluate the efficacy of metronidazole in reducing the risk of post abortal pelvic infection in women with bacterial vaginosis. Design Randomised double-blind placebo-controlled trial. Setting Two teaching hospitals and one district general hospital. Sample Two hundred and seventy-three women with bacterial vaginosis undergoing termination of pregnancy. Methods Women with bacterial vaginosis, diagnosed using modified Spiegel's criteria, were individually randomised to receive either a 2 g metronidazole suppository or identical placebo per-operatively. Participants, doctors and investigators were blinded to treatment allocation. Participants were asked to complete a questionnaire about post-operative symptoms, visits to the general practitioner, antibiotic treatment, readmission to hospital, contraception and emotional response after one month. Results The prevalence of bacterial vaginosis was 29.3% (326/1111). Intention-to-treat analysis showed that post-operative upper genital tract infection developed in 12/142 (8.5%) women allocated to metronidazole and 21/131 (16.0%) women randomised to placebo, a difference of 7.6% (95% confidence intervals –15.4 to +0.2%; relative risk 0.53, 0.27 to 1.03, P = 0.055). The effect of prophylaxis was similar when the analysis was restricted to women receiving the allocated treatment and with complete follow up. There was no difference in the risk of readmission to hospital and the frequencies of self reported symptoms in the two groups were similar. Conclusion This randomised placebo-controlled trial among women with bacterial vaginosis provides weak evidence that metronidazole decreases the risk of upper genital tract infection after first trimester suction termination of pregnancy but a chance finding could not confidently be excluded. Large well-conducted randomised trials with long term outcome measures are now needed to determine the most effective antibiotic combinations and strategy for prevention of post-abortal pelvic infection.

In this report, the authors present two cases of accidental death in children of addicted parents. In the first case, the child was left unattended at home while the mother went out to buy cocaine. She was arrested and detained with no mention of the unsupervised child. The cause of death in this case was determined to be starvation and dehydration. In the second case, a child mistakenly received a methadone suppository by her father instead of an antipyretic suppository. Toxicological analysis of the femoral blood revealed methadone at a concentration of 1.2 mg/L. The cause of death was determined to be methadone intoxication. The literature is reviewed and discussed. We report these cases to illustrate the risk of harm to children from illicit drugs and prescription medications at home and because there is no mention of accidental death in children following a methadone suppository administration in the current literature. Language: en

Study Objective. To compare phenytoin pharmacokinetics following administration of an oral suspension and a rectal suppository formulated with a polyethylene glycol base. Design. Unblinded, single-dose, randomized, crossover trial. Setting. University-affiliated pharmacokinetics and biopharmaceutics laboratory. Subjects. Six healthy subjects. Intervention. Subjects were given a single 200-mg dose of phenytoin as an oral suspension and a rectal suppository separated by a 1-week washout. Measurements and Main Results. Blood for plasma phenytoin concentrations was obtained at baseline and 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration. Plasma was analyzed by high-performance liquid chromatography (coefficient of variation < 6%) for total phenytoin concentration. Phenytoin maximum concentration (Cmax), time to Cmax (Tmax), time to first measurable concentration (Tlag), and area under the curve from time zero to time of last measurable concentration (AUClast) were estimated for oral and rectal administration by WinNonlin (v 1.1) and compared using Wilcoxons signed rank test (p

BACKGROUND This study examined the effect of tegafur, a depot of 5-fluorouracil, in human colorectal carcinomas in terms of apoptosis, cell proliferation, and expression of p53 gene and angiogenesis-related molecules. METHODS A total of 32 patients with colorectal carcinoma were divided into 2 groups; 20 patients received tegafur suppositories (TS) at 1 g/day for 14 days before surgery, and 12 patients did not receive any chemotherapy. Surgically removed specimens were examined immunohistochemically for Ki-67, CD34, p53, p21, Bax, vascular endothelial growth factor (VEGF), and thymidine phosphorylase (dThdPase). Apoptotic tumor cells were visualized by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick-end labeling (TUNEL) procedure. RESULTS The mean percentage of apoptotic index (AI) was 6.9 ± 1.2 in the 20 TS-treated tumors and 4.4 ± 1.0 in the 12 nontreated tumors (P < 0.001). In contrast, the mean percentage of Ki-67 labeling index (KI) became significantly lower in the former group (P < 0.05). The frequency of p21 expression was significantly higher in the TS-treated group than in the nontreated group (P < 0.05), whereas no difference was detected in p53 and Bax expression between the two groups. The mean intratumoral microvessel density was 47.8 ± 19.8 in the TS-treated tumors and 66.8 ± 16.5 in the nontreated tumors (P < 0.01). The frequency of dThdPase expression, but not of VEGF expression, became significantly lower with the TS treatment. p53 expression did not correlate with AI, KI, IMV density, or the expression of VEGF, p21, or Bax, except for dThdPase, which was significantly higher in the 18 p53 positive tumors (P < 0.05). CONCLUSIONS Preoperative TS treatment enhances apoptosis and suppresses angiogenesis of colorectal carcinomas in a p53-independent manner. Cancer 2000;88:1007–15. © 2000 American Cancer Society.

Codeine is frequently used for postoperative analgesia in children. Intramuscular injections are not ideal and the rectal route may be preferable. We compared rectal and intramuscular codeine administered following neurosurgery. 20 children (over 3 months) undergoing elective neurosurgical procedures, were randomized to receive either rectal or intramuscular codeine phospate (1 mg.kg-1) at the end of the procedure. Serum levels of codeine and morphine were assayed at intervals following administration (0, 30, 60, 120, 240 min). Fentanyl was the intraoperative analgesic and postoperative rescue analgesia was paracetamol, diclofenac and intramuscular codeine. The Children's Hospital of Eastern Ontario Pain Scale was used to assess analgesia. Peak codeine levels in both groups were observed at 30 min and morphine levels were consistently low. The plasma codeine levels were significantly greater at 30 and 60 min following intramuscular injection, and were associated with slightly better analgesia scores, but did not reach statistical significance. However, the peak plasma level occurred at similar times in both groups. Codeine is absorbed as rapidly via the rectal route compared with the intramuscular route but the peak levels are lower.

Objective: To determine the relative bioavailability and plasma paracetamol concentration profiles following administration of a proprietary formulation of paracetamol suppositories to postoperative children. Methodology and Results: Study A—eight children undergoing minor surgery had blood samples collected following the rectal administration of either a 250 mg or 500 mg paracetamol suppository on one day and an equivalent oral dose on the following day. A mean dose of 13 mg/kg gave a mean Cmax (Tmax) of 7.7 mg/L (1.6 h) and 4.9 mg/L (2.0 h) following oral and rectal administration, respectively. The mean relative rectal bioavailability was 78% (95% confidence interval of 55–101%). Study B—20 children undergoing tonsillectomy and/or adenoidectomy were randomly assigned to receive a postoperative dose of 500 mg of paracetamol either as 2×250 mg liquid filled or 1×500 mg hard wax Panadol® suppository. A mean dose of 25 mg/kg produced mean maximum plasma paracetamol concentrations of 13.2 mg/L and 14.5 mg/L at 2.1 and 1.9 h for the hard and liquid filled suppository, respectively. The absorption rate constants and areas under the curves suggested no difference in the rate or extent of absorption between the two formulations. Conclusion: Absorption of paracetamol following rectal administration of Panadol® suppositories to postoperative children is slower and reduced as compared to oral therapy. The hard wax and liquid filled products have similar absorption characteristics. The usually quoted antipyretic therapeutic range for paracetamol is 10–20 mg/L, although 5 mg/L may be effective. A single rectal dose of 25 mg/kg will obtain this lower concentration within 1 h of administration and maintain it for up to 6 h. When given in an appropriate dose for analgesia, maximum plasma paracetamol concentrations would be available in the immediate postoperative period if the rectal dose was given 2 h before the planned end of the procedure.

BACKGROUND: Symptomatic postural hypotension in diabetes is uncommon. When it does occur, it can prove debilitating and difficult to treat. We report here the therapeutic challenges encountered in managing a patient with severe postural hypotension secondary to diabetes-related autonomic neuropathy. CASE REPORT: A 69-year-old gentleman with a 23-year history of Type 1 diabetes mellitus and multiple microvascular complications was admitted with symptoms of severe postural hypotension. Cardiovascular autonomic testing confirmed the presence of severe autonomic neuropathy. He failed to respond to non-pharmacological measures, fludrocortisone, midodrine, octreotide, erythropoietin and increased caffeine intake. Eventually he was commenced on half a Cafergot suppository (giving him a dose of ergotamine 1 mg and caffeine 50 mg) which resulted in dramatic clinical improvement. CONCLUSION: Ergotamine may be considered in refractory cases of postural hypotension.

A pharmacokinetic dynamic simulation model was used to predict rectal paracetamol dosing schedules which would maintain steady state plasma concentrations of 10-20 mg.l-1. These plasma concentrations of paracetamol are known to reduce fever. The conventional dosing schedule of 15 mg.kg-1 four hourly was unsatisfactory. Steady state concentrations of 8-12 mg.l-1 were only reached after 16 h. A loading dose of 50 mg.kg-1 followed by 30 mg.kg-1 six hourly achieved plasma concentrations of 9-18 mg.l-1. Paracetamol is a mild analgesic. A higher plasma paracetamol concentration of 25 mg.l-1 is known to give satisfactory analgesia to 60% of children after tonsillectomy. This concentration can be reached after a loading dose of 70 mg.kg-1 and a maintenance dose of 50 mg.kg-1 8 hourly. Doses above 150 mg.kg-1.day-1 have been reported to cause reversible liver toxicity after 2-8 days and should not be sustained.

Department of Gastroenterology, University Hospital Maastricht, The Netherlands. BACKGROUND: Cisapride has an established prokinetic effect in patients with delayed gastric emptying. However, rectal administration of the drug might be preferred in patients with either dysphagia or nausea due to gastroparesis. AIM: To determine the effect of a single rectal dose of cisapride 60 mg on gastric emptying in patients with delayed gastric emptying. METHODS: Thirty-two patients (16 males, 16 females) with demonstrated delayed gastric emptying received a single dose of two suppositories containing either cisapride (2 x 30 mg) or placebo, according to a double-blind randomized crossover design. Three hours after administration of the suppositories, the patients received a radio-labelled test meal and radio-opaque markers for measurement of gastric emptying. RESULTS: The mean t1/2 after cisapride administration (76 min, 95% CI: 68-95) was significantly shorter (P = 0.005: n = 28, per-protocol analysis) than after placebo administration (104 min, 81-126). Four hours after ingestion of the meal significantly fewer radio-opaque markers remained in the stomach after cisapride than after placebo administration (P < 0.05). Mild to moderate adverse events, mainly involving the gastrointestinal tract, were reported in 10 patients (31%) after cisapride treatment and in four patients (13%) after placebo (N.S.: n = 32). CONCLUSION: A single suppository dose of cisapride 60 mg significantly accelerates gastric emptying of the solid phase of a meal and of radio-opaque markers in patients with previously demonstrated delayed gastric emptying. Publication Types: Clinical Trial Randomized Controlled Trial

Background: Topical treatments with steroids or mesalazine are the most effective treatments for idiopathic proctitis. Aim: to compare the efficacy and tolerance of mesalazine suppositories vs. hydrocortisone acetate foam in the treatment of acute proctitis. Patients and methods: 242 patients with active idiopathic proctitis were randomized to receive once daily either one Pentasa suppository (mesalazine 1 g) or 100 mg hydrocortisone (Colofoam) for 14–21 days (until remission). Disease activity and tolerance of the treatments were assessed using a daily questionnaire, by physician assessment, and endoscopy score. Results: Both treatments induced a significant reduction in disease activity. Mesalazine suppositories were significantly more effective than hydrocortisone on rectal blood loss (P=0.002) and mucus (P=0.02) parameters, and on the degree of the decrease in endoscopy score (P=0.02). No significant difference was observed between treatments concerning histology or tolerance. Conclusion: Mesalazine suppositories were as well-tolerated as hydrocortisone foam, but were more effective for some parameters of disease activity.

OBJECTIVES To evaluate, in a randomized prospective study, the efficiency of transrectal lidocaine suppositories to reduce pain during transrectal prostate biopsy, as suppositories allow longer for the agent to be effective. PATIENTS AND METHODS In all, 100 patients were randomized to receive either a placebo suppository or 10 mL of 2% (200 mg) lidocaine gel rectally 10 min before biopsy, or a suppository containing 60 mg lidocaine 1 or 2 h before biopsy. Costs (in euros) per application were 0.82 for gel and 0.63 for suppositories. In all patients the same 10-core biopsy technique was used. Pain was evaluated using a visual linear pain scale ranging from 0 to 100 points; the patient's side of the scale did not show the number of points. RESULTS The mean pain scores in the placebo, lidocaine gel, and lidocaine suppositories applied 1 h and 2 h before biopsy were 36.2, 40.9, 29.2 and 21.2, respectively. Thus patients with no anaesthesia reported 25% more pain than those receiving lidocaine suppositories 1 h before and 71% more pain than those receiving lidocaine suppositories 2 h before biopsy (P = 0.002). CONCLUSIONS Lidocaine suppositories at a lower dose and with longer to take effect can be used to reduce pain significantly more effectively than the commonly used gel. As suppositories are easy to use and cheap, they are recommended in daily routine prostate biopsy.

BACKGROUND Oral sulindac is known to reduce polyps in patients with familial adenomatous polyposis (FAP). The authors speculated that rectal administration of indomethacin would be effective therapy for adenomas in the rectal remnant of FAP. METHODS Eight patients with FAP who had been treated by total colectomy with ileorectal anastomosis were administered an indomethacin suppository (50 mg) once or twice daily during a period of 4 or 8 weeks. The number of polyps at the same site within the rectum was counted under proctoscopy prior to, at the end of, and after the treatment. In four patients, proliferative activity of the rectal mucosa was assessed by immunohistochemical staining for MIB-1. RESULTS In six of the eight patients who initially had ten or more polyps, the number of polyps decreased to fewer than five, whereas such a decrease could not be observed in the remaining two patients. In the six patients, the number of polyps increased after indomethacin was discontinued. The proliferative activity of the rectal mucosa was higher at the end of treatment than it was prior to indomethacin administration. CONCLUSIONS Indomethacin suppositories may be effective in the management of rectal adenomatosis in patients with FAP. Cancer 1996;78:1660-5.

Six healthy mares ranging in age from 6 to 12 years and weighing from 415 to 540 kg were used to determine the rectal bioavailability of ketoprofen. For the rectal administration, three different formulations, each containing 1 g of ketoprofen, were administered in a fatty and a hydrophilic suppository base and as a liquid suspension. An average elimination half-life of 1.3 h (+/-1.2) was found. The average value for the total plasma clearance (ClT) was 131.9mL/ min.kg (range 95-183.5). The volume of distribution Vd(area) was 255 mL/kg and the mean residence time (MRT) value was 0.47 h. After rectal administration, the mean maximal plasma ketoprofen concentrations were 1.6(+/-0.8), 1.1(+/-0.7) and 1.6(+/-0.2) micrograms/mL for the fatty suppository, the hydrophilic suppository and the liquid suspension respectively. The absolute bioavailability of ketoprofen in horses after rectal administration of the three formulations was relatively low, with a large interindividual variability (24.5 +/- 9.5%, 28.7 +/- 18% and 31.3 +/- 6.8% for the fatty suppository, the hydrophilic suppository and the liquid suspension respectively). These values were not significantly different (P = 0.05; Friedman test). Despite the low rectal bioavailability obtained in this study, there was some evidence for the clinical effectiveness of the rectal formulations.