Reduced Ulcer Size Research Articles

Use of proton pump inhibitors in the management of gastroesophageal varices: a systematic review.

To review the efficacy and safety of proton pump inhibitors (PPIs) in gastroesophageal varices (GEVs). MEDLINE (1946 to September 2014), EMBASE (1974 to September 2014), International Pharmaceutical Abstracts (1970 to September 2014), Cochrane Central Register of Controlled Trials (1991 to September 2014), Google, and Google Scholar were searched using the following terms: esophageal varices, gastroesophageal varices, variceal hemorrhage, variceal bleeding, banding ligation, endoscopic variceal ligation, sclerotherapy, proton pump inhibitor, PPI, omeprazole, pantoprazole, lansoprazole, dexlansoprazole, rabeprazole, and esomeprazole. Published and unpublished studies evaluating the clinical outcomes of PPI use for GEVs were included regardless of study design. Non-English and nonhuman studies were excluded. Of 1156 studies, 20 were included after assessment. There was wide methodological heterogeneity and moderately high risk of bias among studies. Level I evidence suggests that PPIs reduce esophageal ulcer size post-elective esophageal ligation; the clinical importance of such findings is not known given the self-limiting nature of esophageal ulcer. Available evidence does not support a role of PPIs for long-term prophylaxis of portal hypertension-related bleeding and high-dose infusion for acute management of GEV hemorrhage. Retrospective data demonstrate a potential increase in the incidence of spontaneous bacterial peritonitis in patients with cirrhosis receiving PPIs. The best available evidence supports the use of short-course (10 days) PPI post-endoscopic variceal ligation to reduce ulcer size if ulcer healing is a concern. Practices such as high-dose infusion and prolonged use should be discouraged until evidence of benefit becomes available.

The REDUCE pivotal trial: a prospective, randomized controlled pivotal trial of a dual intragastric balloon for the treatment of obesity

BackgroundSaline-filled intragastric balloon devices are reversible endoscopic devices designed to occupy stomach volume and reduce food intake. Objective: To evaluate the safety and effectiveness of a dual balloon system plus diet and exercise in the treatment of obesity compared to diet and exercise alone. Setting: Academic and community practice, United States. MethodsParticipants (n = 326) with body mass index (BMI) 30–40 kg/m2 were randomized to endoscopic DBS treatment plus diet and exercise (DUO, n = 187) or sham endoscopy plus diet and exercise alone (DIET, n = 139). Co-primary endpoints were a between-group comparison of percent excess weight loss (%EWL) and DUO subject responder rate, both at 24 weeks. Thereafter DUO patients had the DBS retrieved followed by 24 additional weeks of counseling; DIET patients were offered DBS treatment. ResultsMean BMI was 35.4. Both primary endpoints were met. DUO weight loss was over twice that of DIET. DUO patients had significantly greater %EWL at 24 weeks (25.1% intent-to-treat (ITT), 27.9% completed cases (CC, n = 167) compared with DIET patients (11.3% ITT, P = .004, 12.3% CC, n = 126). DUO patients significantly exceeded a 35% response rate (49.1% ITT, P<.001, 54.5% CC) for weight loss dichotomized at 25%EWL. Accommodative symptoms abated rapidly with support and medication. Balloon deflation occurred in 6% without migrations. Early retrieval for nonulcer intolerance occurred in 9%. Gastric ulcers were observed; a minor device change led to significantly reduced ulcer size and frequency (10%). ConclusionThe DBS was significantly more effective than diet and exercise in causing weight loss with a low adverse event profile.

Interventions for treating leg ulcers in people with sickle cell disease.

The frequency of skin ulceration makes it an important contributor to the morbidity burden in people with sickle cell disease. Many treatment options are available to the healthcare professional, although it is uncertain which treatments have been assessed for effectiveness in people with sickle cell disease. To assess the clinical effectiveness and safety of interventions for treating leg ulcers in people with sickle cell disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.We searched LILACS (1982 to August 2012), the African Index Medicus (up to August 2012), ISI Web of Knowledge (1985 to August 2012), and the Clinical Trials Search Portal of the World Health Organization (August 2012). We checked the reference lists of all the trials identified. We also contacted those groups or individuals who may have completed relevant randomised trials in this area.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 21 July 2014; date of the last search of the Cochrane Wounds Group Trials Register: 18 September 2014. Randomised controlled trials of interventions for treating leg ulcers in people with sickle cell disease compared to placebo or an alternative treatment. Two authors independently selected studies for inclusion. All three authors independently assessed the risk of bias of the included studies and extracted data. Six studies met the inclusion criteria (198 participants with 250 ulcers). Each trial investigated a different intervention and within this review we have grouped these as systemic pharmaceutical interventions (L-cartinine, arginine butyrate, isoxsuprine) and topical pharmaceutical interventions (Solcoseryl(®) cream, RGD peptide dressing, topical antibiotics). Three interventions reported on the change in ulcer size (arginine butyrate, RGD peptide, L-cartinine). Of these, RGD peptide matrix significantly reduced ulcer size compared with a control group, mean reduction 6.60cm(2) (95% CI 5.51 to 7.69; very low quality of evidence). Three trials reported on the incidence of complete closure (isoxsuprine, arginine butyrate, RGD peptide matrix; ranging between low and very low quality of evidence). None reported a significant effect. No trial reported on: the time to complete ulcer healing; ulcer-free survival following treatment for sickle cell leg ulcers; quality of life measures; or incidence of amputation. There was no reported information on the safety of these interventions. There is evidence that a topical intervention (RGD peptide matrix) reduced ulcer size in treated participants compared to controls. This evidence of efficacy is limited by the generally high risk of bias associated with these reports.We planned to analyse results according to general groups: pharmaceutical interventions (systemic and topical); and non-pharmaceutical interventions (surgical and non-surgical). However, we were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between the unit of randomisation and the unit of analysis. This heterogeneity, along with a paucity of identified trials, prevented us performing any meta-analyses.This Cochrane review provides some evidence for the effectiveness of one topical intervention - RGD peptide matrix. However, this intervention was assessed as having a high risk of bias due to inadequacies in the single trial report. Other included studies were also assessed as having a high risk of bias. We recommend that readers interpret the trial results with caution. The safety profile of the all interventions was inconclusive.

Acemannan, a Polysaccharide Extracted fromAloe vera,Is Effective in the Treatment of Oral Aphthous Ulceration

The objective of this study was to elucidate the safety and effectiveness of acemannan, a polysaccharide extracted from Aloe vera, in the treatment of oral aphthous ulceration. A skin patch test was performed on 100 healthy subjects, and 0.5% acemannan in Carbopol® 934P NF (Lubrizol Corporation, USA) was applied to the oral mucosa of the lower lip of 50 healthy participants 3 times/day for 7 days. Oral examinations and blood tests measuring liver and kidney function were performed prior to, and following, 7 days of application to assess the side-effects of acemannan when used on oral mucosa. Another 180 subjects with recurrent aphthous ulceration randomly received one of three treatments: 0.1% triamcinolone acetonide (HOE Pharmaceuticals, Malaysia), 0.5% acemannan in Carbopol® 934P NF, or pure Carbopol® 934P NF. Medications were applied to the ulcers 3 times/day for 7 days. Measurements of ulcer size and patient satisfaction ratings were performed on days 2, 5, and 7. Pain ratings were recorded daily. No subjects exhibited allergic reactions or side-effects to acemannan. There were no significant differences between the blood test values before and after 7 days of acemannan application. The effectiveness of acemannan in reducing ulcer size and pain was superior to that of control, but inferior to that of 0.1% triamcinolone acetonide. Patients were mostly satisfied with 0.1% triamcinolone acetonide and acemannan treatment. Acemannan can be used for the treatment of oral aphthous ulceration in patients who wish to avoid the use of steroid medication, although the effectiveness was not comparable to that of 0.1% triamcinolone acetonide.

Promising results for dexamethasome ointment for treatment of recurrent aphthae

Randomised controlled trial. Patients were randomised to receive either a 5 g tube of dexamethasone ointment (containing 5 mg dexamethasone) [n=120] or placebo ointment [n=120]. Participants were instructed to apply the given agents to the ulcer three times a day (after meals) for five days. The initial application of the medication was performed under observation for >30 minutes for any signs of adverse effects. Patients kept a daily log and were reviewed clinically on day 6 ± 2. The size, pain level, healing ratio, average duration of ulcers and the safety of the agents were evaluated. The serum concentration of dexamethasone was monitored. After 6 ± 2 days of treatment, there was significant difference in the ulcer size between the treatment group (7.167± 6.3415 mm²) and the control group (4.346 ± 7.0666 mm²; P=.000), and in the variation of pain level between the treatment group (5.623± 1.9570) and the control group (4.940± 2.2449; P=.001). The healing ratio was 83.33% in the treatment group and 54.70% in the control group (P=.000). No severe adverse reactions were observed. No serum dexamethasone was detected before or after the use of the agents (<0.502 ng/mL). The current study revealed that dexamethasone ointment was safe and efficient in reducing ulcer size, alleviating ulcer pain and hastening ulcer healing in patients with recurrent aphthous ulceration. In addition, the patients had a good overall assessment of the agents. We could not detect dexamethasone in the serum of patients, which illustrated further the safety of dexamethasone ointment.

Clinical evaluation of allicin oral adhesive tablets in the treatment of recurrent aphthous ulceration

We investigated the effectiveness and safety of topical application of 5 mg allicin adhesive tablets in the treatment of minor recurrent aphthous ulcerations (MiRAU). A randomized, double-blinded, placebo-controlled, clinical trial was performed. Tablets containing 5 mg allicin or vehicle only were consecutively applied 4 times per day for 5 days. The size and pain level of ulcers were measured and recorded on days 1, 2, 4, and 6. A total of 96 subjects with MiRAU fulfilled the study. Allicin adhesive tablets significantly reduced ulcer size (P < .005, P < .003, P < .001 for days 2, 4, and 6, respectively) and alleviated ulcer pain score (P < .03, P < .001, P < .05 for days 2, 4, and 6, respectively) compared with vehicle tablets. Minor and major adverse reactions were not observed. Allicin adhesive tablets were effective in reducing ulcer size and alleviating ulcer pain of the patients in the treatment of MiRAU without significant side effects.

Evaluation of penicillin G potassium troches in the treatment of minor recurrent aphthous ulceration in a Chinese cohort: a randomized, double-blinded, placebo and no-treatment–controlled, multicenter clinical trial

The aim of this study was to explore the effectiveness and safety of topical application of 50 mg penicillin G potassium troches in the treatment of minor recurrent aphthous ulcerations (MiRAU) in a Chinese cohort. A randomized, double-blinded, placebo and no-treatment-controlled, multicenter clinical trial was performed. Troches were consecutively applied 4 times per day for 4 days. The size and pain level of ulcers were measured and recorded on days 0, 3, 4, 5, and 6. A total of 258 subjects with minor recurrent aphthous ulcerations (86 subjects in penicillin G potassium group, 88 subjects in placebo control group, and 84 subjects in no-treatment control group) fulfilled the study. Penicillin G potassium significantly reduced ulcer size (P < .00001 for days 3, 4, 5, and 6) and alleviated ulcer pain (P < .00001 for days 3, 4, 5, and 6). No severe adverse reactions were observed. Only 4 subjects experienced mild adverse reaction. Penicillin G potassium troches are effective in reducing ulcer size and alleviating ulcer pain of the patients in the treatment of a single episode of MiRAU in this Chinese cohort. Few adverse effects were observed with this therapeutic approach.

A clinical evaluation of amlexanox oral adhesive pellicles in the treatment of recurrent aphthous stomatitis and comparison with amlexanox oral tablets: a randomized, placebo controlled, blinded, multicenter clinical trial

BackgroundAmlexanox has been developed as a 5 percent topical oral paste for the treatment of patients with recurrent aphthous stomatitis (RAS) in most European countries. However, it is not yet available in China and has not been generally accepted in clinical treatment. The aim of this study was to explore the effectiveness of amlexanox oral adhesive pellicles in the treatment of minor recurrent aphthous ulcers, and compare the results with those of amlexanox oral adhesive tablets in order to analyse the difference between the two dosage forms of amlexanox.MethodsWe performed a randomized, blinded, placebo-controlled, parallel, multicenter clinical study. A total of 216 patients with minor recurrent aphthous ulcers (MiRAU) were recruited and randomized to amlexanox pellicles or placebo pellicles. Pellicles were consecutively applied four times per day, for five days. The size and pain level of ulcers were measured and recorded on treatment days 0, 4 and 6. Finally, the results were compared with those of our previous 104 cases treated with amlexanox tablets.ResultsAmlexanox oral adhesive pellicles significantly reduced ulcer size (P= 0.017 for day 4, P=0.038 for day 6) and alleviated ulcer pain (P=0.021 for day 4, P=0.036 for day 6). No significant difference was observed in the treatment effectiveness between the pellicle and tablet form of amlexanox.ConclusionsAmlexanox oral adhesive pellicles are as effective and safe as amlexanox oral adhesive tablets in the treatment of MiRAU for this Chinese cohort. However, pellicles seem to be more comfortable to use when compared with the dosage form of tablets. Therefore, in clinical practice, amlexanox oral adhesive pellicles may be a better choice for RAS patients.Trials registrationNederlands Trial Register NTR1727.

Insulin-like growth factor I accelerates gastric ulcer healing by stimulating cell proliferation and by inhibiting gastric acid secretion.

Given the importance of Insulin-Like Growth Factor I (IGF-I) to intestinal maintenance and the presence of IGF-I in salivary glands, we hypothesized that IGF-I participates in the healing of gastric ulcers. The aim of the study was to determine: 1) whether IGF-I applied locally would support gastric ulcer healing by increasing cell proliferation and 2) the effect of IGF-I on gastric acid secretion. Gastric ulcers were induced with a cryoprobe. Immediately thereafter, IGF-I (0.4, 4.0 and 40 microg) or vehicle was infiltrated perifocally. In another group, animals received a daily dose of 40 micromol omeprazole subcutaneously. Ulcer healing was evaluated by ulcer size and histological examination at 7 days. Pentagastrin-stimulated gastric acid secretion was evaluated in conscious rats with gastric fistula, after IGF-I (400 microg) had been injected intravenously. IGF-I significantly reduced ulcer size, but only at low doses (0.4 microg/kg body weight (BW), P = 0.008; 4 microg/kg BW, P = 0.001). This effect was similar to omeprazole treatment. Histological examination after IGF-I administration showed increased cell proliferation, increased IGF-I content and down-regulated IGF-I receptors. The secretory studies demonstrated a significant decrease in gastric acid secretion 30 min after IGF-I bolus injection (IGF-I: 53 +/- 11 microEq; vehicle: 116 +/- 5 microEq; P=0.001), which lasted for more than 1 h. IGF-I stimulates gastric ulcer healing, stimulating cell proliferation and inhibiting gastric acid secretion.

Insulin-Like Growth Factor I Accelerates Gastric Ulcer Healing by Stimulating Cell Proliferation and by Inhibiting Gastric Acid Secretion

Background: Given the importance of Insulin-Like Growth Factor I (IGF-I) to intestinal maintenance and the presence of IGF-I in salivary glands, we hypothesized that IGF-I participates in the healing of gastric ulcers. The aim of the study was to determine: 1) whether IGF-I applied locally would support gastric ulcer healing by increasing cell proliferation and 2) the effect of IGF-I on gastric acid secretion. Methods: Gastric ulcers were induced with a cryoprobe. Immediately thereafter, IGF-I (0.4, 4.0 and 40 µg) or vehicle was infiltrated perifocally. In another group, animals received a daily dose of 40 µmol omeprazole subcutaneously. Ulcer healing was evaluated by ulcer size and histological examination at 7 days. Pentagastrin-stimulated gastric acid secretion was evaluated in conscious rats with gastric fistula, after IGF-I (400 µg) had been injected intravenously. Results: IGF-I significantly reduced ulcer size, but only at low doses (0.4 µg/kg body weight (BW), P = 0.008; 4 µg/kg BW, P

Inhibition of inducible nitric oxide synthase delays gastric ulcer healing in the rat.

We sought to clarify the role of nitric oxide (NO) generated from inducible NO synthase (iNOS) during healing of rat gastric ulcers. After gastric ulcers were induced by acetic acid, rats were treated with vehicle, N(G)-nitro-L-arginine methyl ester (L-NAME), aminoguanidine (AG), and dexamethasone (Dex) by gastric intubation twice a day for 3 days to 1 week. L-NAME significantly delayed healing compared with vehicle. AG and Dex significantly reduced ulcer size 3 days after ulcer induction but did not further reduce ulcer size 1 week after induction. iNOS expression was present in inflammatory cells, some epithelial cells, and in vascular smooth muscle in the regenerating mucosa of the vehicle-treated group. However, the number of iNOS-positive inflammatory cells increased in the AG- and L-NAME-treated groups. AG and L-NAME significantly increased the number of inflammatory cells with endogenous peroxidase and significantly reduced the number of apoptotic inflammatory cells compared with vehicle. In conclusion, inhibition of iNOS increases the number of inflammatory cells in the ulcer margin and delays ulcer healing. These observations suggest that NO generated from iNOS not only participates in ulcer formation but also plays a beneficial role in ulcer healing, in part by the exclusion of iNOS-positive inflammatory cells from the regenerating mucosa.

Basic fibroblast growth factor increases constitutive nitric oxide synthase during healing of rat gastric ulcers.

The purpose of this study was to clarify the effect of basic fibroblast growth factor (bFGF) on nitric oxide (NO) synthesis during healing of rat gastric ulcers. After experimental gastric ulcers were induced by acetic acid, rats were treated with vehicle, recombinant human bFGF (CS23, 10 micrograms/kg) and NG-nitro-L-arginine methyl ester (L-NAME, 1 mg/kg), an NO synthase (NOS) inhibitor, through an orogastric tube twice daily for 3 days or 1 week. CS23 significantly reduced ulcer size, and L-NAME significantly delayed healing compared with the vehicle group and significantly inhibited the efficacy of CS23. Although constitutive NOS (cNOS) activity significantly decreased and inducible NOS (iNOS) activity significantly increased in the vehicle group, CS23 significantly inhibited these changes. cNOS immunoreactivity on the vessels and neurons disappeared in the vehicle group, and newly formed vessels as well as neurons were observed with positive endothelial and neuronal NOS immunoreactivity in the CS23-treated group. External administration of bFGF accelerated ulcer healing, with recovery of NO synthesis in both endothelial cells and neurons. These observations suggested that increased NO synthesis with angiogenesis and reinnervation has a beneficial effect on gastric ulcer healing.