Biomedical subjects

Yehuda Chowers

Publications and source records attributed to Yehuda Chowers.

At least 19 recordsLinked to original sources

PubMed2007

Failure of Synbiotic 2000 to prevent postoperative recurrence of Crohn's disease.

Complications of Crohn's disease (CD) lead to surgery in about 70-90% of patients. The majority of patients suffer from relapse of the disease. Colonic bacteria are essential to the development of CD. Therefore, a rationale exists in trying to prevent relapse by manipulation of gut microflora. This is feasible by treatment with probiotics or antibiotics. Synbiotic 2000 is a cocktail containing 4 probiotic species and 4 prebiotics. It is rational to pursue that it could be effective in preventing postoperative disease. We sought to check weather treatment with Synbiotic 2000 could prevent postoperative recurrence in patients with CD. This was a prospective multicenter, randomized study. Patients were randomized to active treatment or placebo in a 2:1 ratio. Follow-up consisted of endoscopic, clinical, and laboratory parameters. Thirty patients were enrolled. No differences were found between the 2 treatment groups regarding gender, age at diagnosis, age at surgery, weight, smoking status, type of disease, length of the resected segment, or medical treatment prior to surgery. No difference in either endoscopic or clinical relapse rate was found between patients treated with once daily dose of Synbiotic 2000 or placebo. In our small study, Synbiotic 2000 had no effect on postoperative recurrence of patients with CD. Larger studies in patients with the inflammatory type of CD undergoing surgery, using higher doses of probiotics cocktail might prove effective.

Adult↗

PubMed2007

Long-standing colonic inflammation is associated with a low prevalence of diverticuli in inflammatory bowel disease patients.

BACKGROUND: Diverticulosis is associated with high intracolonic pressure and a weakened bowel wall. Chronic colitis is characterized by liquid stools suggestive of low intracolonic pressure and a thickened bowel wall. Therefore, the aim of this study was to assess the prevalence of diverticulosis in colitis patients. METHODS: Colonoscopy results of patients with inflammatory bowel disease (IBD)-associated colitis older than 50 years were retrospectively evaluated and compared with those of patients who underwent screening colonoscopy. Only patients with biopsy-proven disease, disease duration of more than 5 years, and disease beyond the distal 20 cm were included. RESULTS: In all, 1037 patients were diagnosed by colonoscopy as suffering from IBD-associated colitis between 1987-2005. After exclusion of patients who did not meet the inclusion criteria the study population consisted of 314 IBD patients and 1023 age-matched control patients. A significantly higher percent of diverticuli was detected in the control group compared with the IBD group (15% versus 3.5%, P < 0.001). No significant difference in the prevalence of diverticuli was detected between the three subtypes of IBD patients (2% in ulcerative colitis versus 4.7% in Crohn's colitis versus 7.6% in indeterminant colitis). Neither disease duration nor the specific colonic segment involved had a significant influence on the prevalence of diverticulosis. CONCLUSIONS: Long-standing colonic inflammation in IBD patients is associated with a lower prevalence of diverticuli.

Colitis↗

PubMed2006

TNF-857 polymorphism in Israeli Jewish patients with inflammatory bowel disease.

Tumour necrosis factor (TNF)-alpha is an important pro-inflammatory cytokine that has been implicated in the pathogenesis of inflammatory bowel disease (IBD). The promoter TNF-857 C-->T single nucleotide polymorphism (SNP) is functional through the binding to the transcription factor octamer transcription factor-1 (OCT-1). In order to investigate the frequency of this SNP in Israeli Jewish IBD patients, we analysed a cohort of well-characterized patients, 153 with Crohn's disease (CD) and 78 with ulcerative colitis (UC) and 188 healthy controls individually matched for age, sex and ethnicity. Forty-one per cent of the patients were of Ashkenazi and 48% were of non-Ashkenazi background. The remaining 11% were of mixed Ashkenazi-non-Ashkenazi background. Patients and controls were genotyped for the TNF-857 SNP by Taqman technology. Stratification for the CARD15 Arg702Trp, Gly908Arg and Leu1007fsinsC mutations took place in 136 CD patients. Carrier frequency of TNF-857T between CD and controls (36% vs. 40%; P = 0.556; OR: 1.18, 95% CI 0.74-1.88), or between UC and controls (41% vs. 37%; P = 0.743; OR: 0.85, 95% CI 0.45-1.62) did not differ significantly. Neither did stratifying for the presence of at least one of the common CARD15 mutations result in a significant difference between CD and controls. No associations were found between TNF-857T and CD phenotype as defined by the Vienna classification, perianal disease or extra-intestinal disease irrespective of CARD15 carrier status. In conclusion, it appears that TNF-857 SNP does not contribute to susceptibility of IBD, neither does it define the phenotype of CD in Israeli Jewish IBD patients.

Adult↗

PubMed2006

[Infliximab in inflammatory bowel diseases--conference summary and suggested guidelines].

Infliximab, the monoclonal anti-tumor necrosis factor-alpha (TNF-alpha) antibodies preparation, is efficacious in the treatment of inflammatory bowel diseases. However, the optimal therapeutic approach is still under investigation. Reports on side effects and potential complications of infliximab therapy, as well as of other anti-TNF-alpha blocking agents are accumulating. Hence, the Israeli Gastroenterological Association had initiated a conference in order to discuss the frequent clinical issues that have arisen following the use of infliximab for the treatment of inflammatory bowel diseases. The aim was to report on the published clinical experience and problems regarding several practical aspects of the use of Infliximab, to suggest guidelines that are evidence-based and to discuss them with experienced IBD-oriented gastroenterologists. The subjects that were discussed include: (1) treatment protocols; (2) maintenance therapy in Crohn's disease; (3) prevention of infections and (4) therapeutic potential in ulcerative colitis. These topics reflect everyday issues that gastroenterologists deal with while treating inflammatory bowel disease patients. The manuscript summarizes the literature and evidence that were presented in the conference, the points raised at the discussions as well as guidelines suggested by work groups that were established for each subject. These guidelines may assist and direct the gastroenterologist treating inflammatory bowel disease patients with infliximab.

Antibodies, Monoclonal↗

PubMed2005

Increasing the infliximab dose is beneficial in Crohn's disease patients who responded to a lower dose and relapsed.

BACKGROUND: Relapse after an initial response to infliximab therapy poses a problem for maintenance treatment. AIM: To assess the effects of increasing the infliximab dosage in Crohn's disease (CD) patients who initially responded but flared during maintenance therapy. METHODS: This was an observational study. Twelve CD patients with both inflammatory and fistulizing manifestations were included. All patients initially responded to 5 mg/kg of infliximab, relapsed during maintenance therapy, and were treated with 10 mg/kg. The Harvey-Bradshaw index, the fistula activity, and steroid use were assessed before and after treatment with the increased dose of infliximab. RESULTS: The mean Harvey-Bradshaw index score after flare-up during treatment with 5 mg/kg of infliximab was 13.5+/-3.7. Treatment with 10 mg/kg, in a mean of 3.3 infusions, decreased the activity score to a mean of 8.8+/-2.5. Two patients were weaned off prednisone, and a reduced dose was possible in the other steroid-treated patients. CONCLUSIONS: Increasing the infliximab dose may be beneficial in CD patients who initially responded to therapy, but relapsed during maintenance with the lower dosage.

Adult↗

PubMed2005

Endosonographic evaluation of perianal fistulas and abscesses: comparison of two instruments and assessment of the role of hydrogen peroxide injection.

PURPOSE: The aims of this study were to compare the performance of a mechanical radial endosonoscope and an endorectal electronic probe and to evaluate the value of hydrogen peroxide (H(2)O(2)) injection in the diagnosis of perianal fistulas. PATIENTS AND METHODS: Sixty-one patients underwent clinical and endosonographic studies for suspected perianal fistulas or abscesses. Endosonography was performed using two instruments: a mechanical radial endosonoscope (Olympus GF-UM20) and an electronic endorectal probe (Hitachi EUP-R53). The patients were re-examined during and following H(2)O(2) injection using both systems. RESULTS: Thirty-seven fistulous tracts were visualized with the electronic endorectal probe versus only 9 with the mechanical radial endosonoscope. Four patients had anal stenosis, precluding the use of the larger electronic probe. Three fistulas were detected in these patients using the mechanical radial endosonoscope. H(2)O(2) injection was not feasible in 26 patients (43%). Visualization of 11 (31%) fistulas improved after administration of H(2)O(2). Six fistulous tracts not detected before H(2)O(2) administration were clearly visualized during injection and for several minutes thereafter. CONCLUSIONS: Work-up of perianal fistula should be preferably performed using the endorectal electronic probe. However, the mechanical radial endoscope is preferred in patients with anal stricture. H(2)O(2) injection should become an integral part of every sonographic study of perianal fistulas.

Abscess↗

PubMed2005

Somatostatin inhibits pro-inflammatory cytokine secretion from rat hepatic stellate cells.

BACKGROUND/AIMS: Activated hepatic stellate cells (HSCs) have been implicated in hepatic fibrosis. Somatostatin (SOM) has an immunomodulatory role. The aim of this study was to assess the secretion of pro-inflammatory cytokines by HSCs and to determine the effect of SOM on the secretion of these mediators. METHODS: Activated rat HSCs were evaluated for their secretion of IL-1beta, IL-8, and TNF-alpha using ELISA. RNA protection assay was used to determine cytokine mRNA levels. The expression of chemokine and cytokine mRNA and the secretion of these mediators were assessed following incubation with SOM or octreotide. RESULTS: HSCs spontaneously secreted IL-1beta, IL-8, and TNF-alpha. This secretion was augmented following stimulation by IL-1beta and TNF-alpha. SOM inhibited the spontaneous and TNF-alpha-induced secretion of IL-1beta, IL-8, and TNF-alpha and suppressed the expression of IL-1beta and TNF-alpha mRNA. Octreotide suppressed the secretion of IL-1beta and IL-8. CONCLUSIONS: These observations indicate that SOM exerts an inhibitory immunomodulatory effect on HSCs.

Animals↗

PubMed2005

The familial Mediterranean fever (MEVF) gene as a modifier of Crohn's disease.

OBJECTIVES: Crohn's disease (CD) has been reported to be more frequent among non-Ashkenazi Jewish patients suffering from familial Mediterranean fever (FMF). Interestingly, functional similarities between the CD susceptibility gene (NOD2/CARD15) and the FMF gene (MEFV) have been described: both belong to the death domain containing protein family, important in the regulation of apoptosis, cytokine processing and inflammation. AIMS: To investigate the prevalence of MEFV mutations in Jewish non-Ashkenazi CD patients and its putative effect on CD presentation. METHODS: Germline DNA of 105 Israeli CD patients of non-Ashkenazi and mixed Ashkenazi-non-Ashkenazi ethnic background was analyzed for three most common MEFV mutations: M694V, V726A, and E148Q. Five patients (4.7%) with a clinical diagnosis of FMF were included. Data obtained from each patient included: age of onset, disease location, and behavior, the presence of extraintestinal manifestations of CD and therapeutic regimens. RESULTS: The overall prevalence of mutation carriers among non-FMF-CD patients was 13% (13/100). A stricturing disease pattern was observed in 56% (10/18) of all carriers, FMF-CD, and non-FMF-CD patients, and in 25% (22/87) of noncarriers (OR: 3.7, 95% CI: 1.3-10.5, p= 0.015). The prevalence of fistulas was comparable in both groups. Extraintestinal manifestations were significantly more frequent among carriers than noncarriers (65%vs 32%, OR 3.9, 95% CI = 1.3-11.5, p= 0.015). No differences were observed in disease location and disease severity. CONCLUSIONS: MEFV mutations are not associated with CD susceptibility, yet the presence of these mutations appears to be associated with a stricturing disease pattern and extraintestinal disease manifestations of CD.

Adult↗

PubMed2004

Somatostatin analogue treatment attenuates histological findings of inflammation and increases mRNA expression of interleukin-1 beta in the articular tissues of rats with ongoing adjuvant-induced arthritis.

OBJECTIVE: Somatostatin is a neuropeptide with modulatory effects on the immune system and the function of synovial cells; it has antiangiogenic and antiproliferative properties. This study aimed to evaluate the clinical, histological, and articular tissue cytokine mRNA response to somostatin treatment in rat adjuvant-induced arthritis (AIA). METHODS: Adjuvant-induced arthritis was induced in a total of 68 Lewis rats by immunization with complete Freund's adjuvant. Twenty-four rats were treated with a long-acting somostatin analogue 14 days after disease induction. Twenty-four untreated rats served as controls. The severity of arthritis was scored weekly for 42 days. In a second experiment, 20 rats (ten treated, ten controls) were killed 21 days after treatment for assessment of joint histopathology and articular tissue cytokine mRNA expression. RESULTS: Somatostatin analogue treatment significantly reduced histological scores of early inflammatory changes and increased articular tissue mRNA expression of interleukin-1 beta (IL-1beta). A trend toward improvement in physical scores of joint inflammation was seen in the treated group. Late destructive changes were not significantly different. CONCLUSION: Treatment with a somostatin analogue attenuated early inflammatory changes in AIA joints and increased mRNA expression of IL-1beta in the articular tissues of rats with ongoing arthritis. Improvement in the physical findings of joint inflammation was mild.

Animals↗

PubMed2004

Scanning electron microscopy of cells and tissues under fully hydrated conditions.

A capability for scanning electron microscopy of wet biological specimens is presented. A membrane that is transparent to electrons protects the fully hydrated sample from the vacuum. The result is a hybrid technique combining the ease of use and ability to see into cells of optical microscopy with the higher resolution of electron microscopy. The resolution of low-contrast materials is approximately 100 nm, whereas in high-contrast materials the resolution can reach 10 nm. Standard immunogold techniques and heavy-metal stains can be applied and viewed in the fluid to improve the contrast. Images present a striking combination of whole-cell morphology with a wealth of internal details. A possibility for direct inspection of tissue slices transpires, imaging only the external layer of cells. Simultaneous imaging with photons excited by the electrons incorporates data on material distribution, indicating a potential for multilabeling and specific scintillating markers.

Animals↗

PubMed2004

Allicin inhibits spontaneous and TNF-alpha induced secretion of proinflammatory cytokines and chemokines from intestinal epithelial cells.

BACKGROUND & AIMS: Allicin, the active substance of fresh crushed garlic has different biological activities and was implicated as an anti-inflammatory agent. Epithelial cells have an important role in intestinal inflammation. The aim of this study was to assess the immunomodulatory effect of allicin on intestinal epithelial cells. METHODS: The spontaneous and TNF-alpha-stimulated secretion of IL-1beta, IL-8, IP-10 and MIG from HT-29 and Caco-2 cells was tested with, or without pretreatment with allicin. Cytokine secretion was assessed using ELISA and expression of mRNA was determined by an RNA protection assay. RESULTS: Allicin markedly inhibited the spontaneous and TNF-alpha -induced secretion of IL-1beta, IL-8, IP-10 and MIG from the two different cell lines in a dose-dependent manner and suppressed the expression of IL-8 and IL-1beta mRNA levels. In addition, allicin suppressed the degradation of IkappaB. No effect on cell viability was noted. CONCLUSIONS: These observations indicate that allicin exerts an inhibitory immunomodulatory effect on intestinal epithelial cells and suggest that allicin may have the potential to attenuate intestinal inflammation.

Anti-Infective Agents↗

PubMed2004

Colorectal cancer screening in patients presenting with an inguinal hernia: is it necessary?

BACKGROUND: It has been suggested that patients presenting with an inguinal hernia have an increased risk for colorectal cancer. Therefore, surgeons frequently request screening for colorectal cancer before surgery. The aim of this study was to assess the frequency of premalignant and malignant colonic lesions in a group of patients with an inguinal hernia, and to compare this with a control group of subjects undergoing screening colonoscopy. METHODS: In a case-control study, 243 patients with an inguinal hernia and no history of colonic neoplasia or symptoms suggestive of colorectal cancer underwent perioperative colonoscopy. The patients were stratified into two age groups: less than 50 years old (Group I) and more than 50 years old (Group II). The colonoscopic findings were compared with findings in 534 asymptomatic control patients who underwent screening colonoscopy. RESULTS: The mean age of patients (n=64) and control subjects (n=200) in Group I was similar, at 44 (3) years. The mean age of the patients (n=179) and control subjects (n=334) in Group II was, respectively, 70 (9) years and 64 (7) years (p<0.001). In Group I, no colorectal cancer was found in patients with inguinal hernia, and only one colorectal cancer was found among control subjects (p=0.571). In Group II, a diagnosis of colorectal cancer was made in 7 patients (4%) with inguinal hernia as compared with 10 patients (3%) among the control subjects (p=0.769). In both groups, the size and the histopathologic type of the polyps were not significantly different. CONCLUSIONS: In otherwise asymptomatic patients, the presence of inguinal hernia is not associated with an increased risk for colorectal cancer. Therefore, the presence of an inguinal hernia alone does not justify screening colonoscopy before herniorrhaphy.

Adult↗

PubMed2004

Second capsule endoscopy for patients with severe iron deficiency anemia.

BACKGROUND: Patients with iron deficiency anemia are subjected to multiple endoscopic and radiologic examinations of the GI tract. If negative, some of the examinations are repeated, occasionally with positive findings. The diagnostic yield of a second capsule endoscopy in such patients is unknown. The aim of the current study was to assess the diagnostic yield of a second capsule endoscopy in patients with significant iron deficiency anemia and a previous negative evaluation. METHODS: Twenty patients with iron deficiency anemia (Hb < 10 g/dL) were enrolled. All had at least one normal evaluation of the GI tract, including capsule endoscopy. A second capsule endoscopy examination was offered to all patients. RESULTS: The time between the first and the second capsule endoscopy ranged from 2 months to 1 year. Depending on the nature of an abnormality and its relevance to blood loss, the findings were classified as positive, suspicious, clinically irrelevant, or negative. In 7 patients, the second capsule endoscopy disclosed findings that were classified as either positive or suspicious findings, including arteriovenous malformations (2), flat polypoid lesion (1), edematous inflamed mucosa (1), erosions (1), and hemorrhagic gastritis (1). Lesions were located in the small intestine (5), the stomach (1), and the cecum (1). Based on the findings of the second capsule endoscopy, therapy was changed in two patients (10%). CONCLUSIONS: A second capsule endoscopy should be considered for patients with severe iron deficiency anemia and negative initial evaluation.

Adult↗

PubMed2004

The BsmI vitamin D receptor gene polymorphism is associated with ulcerative colitis in Jewish Ashkenazi patients.

Susceptibility to inflammatory bowel disease (IBD) has a strong genetic component. The vitamin D receptor (VDR) gene maps to a region on chromosome 12 shown to be associated with IBD in some studies. In this case-control study we determined the association between the BsmI VDR gene polymorphism and IBD in patients with Crohn's disease (CD) and ulcerative colits (UC). Three hundred seventy-nine Jewish Israeli patients with IBD, 228 with CD (129 Ashkenazi and 99 non-Ashkenazi), and 151 patients with UC (72 Ashkenazi, 79 non-Ashkenazi) were studied. The control group included 495 healthy blood donors (352 non-Ashkenazi and 143 Ashkenazi). All subjects were genotyped for the BsmI VDR gene polymorphism. The frequency of the BB genotype was higher in Ashkenazi patients with UC compared to Ashkenazi controls (0.21 vs. 0.11, p = 0.042, odds ratio 2.27, 95% confidence interval [CI] 1.06-4.9). There were no differences in the prevalence of the BB genotype or the B allele between ethnically matched patients with CD and UC. Nor were there differences in the BB genotype or B allele frequencies between CD patients and ethnically matched controls. The BsmI VDR gene polymorphism is associated with increased susceptibility to UC in Israeli Ashkenazi patients with UC.

Case-Control Studies↗

PubMed2004

The month of birth is linked to the risk of Crohn's disease in the Israeli population.

OBJECTIVE: The main objective is to study whether the month of birth is associated with the development of Crohn's disease (CD) in the Israeli Jewish population. BACKGROUND: It was suggested that perinatal exposure to infectious agents may have a role in the pathogenesis of CD. Due to the seasonal nature of some infections, a linkage between birth dates and a risk to develop CD would support such a hypothesis. Previous studies that addressed this question were conducted in Europe and differed in their findings. METHODS: Birth dates of 844 Jewish ulcerative colitis (UC) and CD patients from three medical centers representing the north, central, and the south of Israel were compared with the monthly rates of birth during the same period of time. The standard incidence ratio was used to define the risk to develop either disease according to the month of birth. The Score method was used for the evaluation of seasonality trends. RESULTS: Birth during the winter period in Israel was associated with increased risk to develop CD, whereas birth during the spring was associated with a reduced risk. The Score method for seasonality showed a significant peak during winter time in these patients (z = 2.02, p= 0.021). No such seasonal variation was noted for UC patients. CONCLUSIONS: A seasonal pattern was observed in the risk to develop CD but not UC. The findings may support the involvement of environmental factors in the pathogenesis of CD.

Adult↗

PubMed2003

Association between mutations in the CARD15 (NOD2) gene and Crohn's disease in Israeli Jewish patients.

Ulcerative colitis (UC) and Crohn's disease (CD) are heterogeneous disorders characterized by chronic intestinal inflammation. Genetic predisposition is a major risk factor in both diseases. The CARD15 (NOD2) gene has been implied as a candidate gene in the pathogenesis CD. Our aim was to delineate the frequency of three missense and one frameshift variant of CARD15 in Israeli Jewish CD and UC patients. DNA was extracted from blood samples from 238 unrelated inflammatory bowel disease (IBD) patients, 68 with UC and 170 with CD. The DNA was genotyped for two missense mutations, R675W and G881R, and one frameshift mutation, 980FS981X. Mutations in CARD15 were observed with significantly greater frequency in CD patients (46/170, 27%) than in UC patients (7/68, 10%) (P = 0.005). Homozygous and compound heterozygous carriers were restricted to seven (4%) patients with CD as compared to none of the UC patients (P = 0.01). Similar rates in Ashkenazi and non-Ashkenazi Jewish patients were observed. Age-of-onset of disease was lower in Ashkenazi mutation carriers as compared to non-carriers of Ashkenazi origin (18.7 +/- 8.6 years vs. 25.8 +/- 13.4 years, respectively, P = 0.03). No other phenotypic characteristics could distinguish mutation carriers from non-carriers. We conclude that germline mutations in the CARD15 gene are more frequently found in CD than UC patients and appear to predict an earlier age-of-onset in Ashkenazi Jewish patients. No association could be demonstrated between CARD15 mutations and specific disease course or behavior.

Adult↗

PubMed2003

Budesonide foam vs. hydrocortisone acetate foam in the treatment of active ulcerative proctosigmoiditis.

INTRODUCTION: Rectal administration of corticosteroids is advocated in patients with proctosigmoiditis who have failed therapy with mesalamine enema. Foam offers patients better tolerability than an enema. In this study the efficacy and adverse effects of a new budesonide foam are compared with the presently available hydrocortisone foam. METHODS: Two hundred fifty-one patients with proctosigmoiditis were randomly assigned to receive either budesonide foam or hydrocortisone foam for eight weeks. RESULTS: Remission rates were comparable in the budesonide and hydrocortisone groups, 53 and 52 percent, respectively. The mean disease activity index for the two groups decreased to a similar extent, from 7.2 +/- 1.9 and 7 +/- 2 to 3.6 +/- 3.1 and 3.9 +/- 3.4 in the budesonide and hydrocortisone groups, respectively. In a subgroup of patients who had not responded to rectal administration of mesalamine, 23 of 44 (52 percent) patients who received budesonide responded favorably to the foam, as compared with 14 of 38 (37 percent) patients who received hydrocortisone (P = not significant). Low plasma cortisol occurred in 3 percent of the budesonide group and in none of the hydrocortisone patients. CONCLUSIONS: This trial demonstrates a similar efficacy and safety of the two foams in patients with proctosigmoiditis.

Administration, Rectal↗

PubMed2003

The optimal dose of 5-aminosalicylic acid in active ulcerative colitis: a dose-finding study with newly developed mesalamine.

BACKGROUND AND AIMS: 5-Aminosalicylate is the gold standard for inducing remission in patients with mildly to moderately active ulcerative colitis. The optimal dose is as yet not defined. Despite some recent developments, the ideal formulation for 5-aminosalicylic acid is still awaited. A new pellet preparation was designed combining slow and delayed release properties. Aims of the study were to find the optimal dose and to test efficacy and safety of a new 5-aminosalicylic acid formulation. METHODS: Three hundred twenty-one patients were included in a double-blind multicenter trial. Inclusion criteria were active ulcerative colitis (Clinical Activity Index [CAI] and Endoscopic Index [EI] according to Rachmilewitz, CAI 6-12; EI >/=4). Three different doses of 5-aminosalicylic acid (0.5 g 3 times a day, 1.0 g 3 times a day, and 1.5 g 3 times a day) were studied for 8 weeks. RESULTS: Clinical remission rate (CAI </=4) was highest in the 1.0 g 3 times a day group (66 %), 50% in the 0.5 g 3 times a day group, and 55% in the 1.5 g 3 times a day group. Hierarchical testing showed no significance, indicating a lack of dose response across the 3 mesalamine doses. In addition, times to first clinical response were similar: 26.5 days (1.0 g 3 times a day), 27.5 days (0.5 g 3 times a day), and 21.5 days (1.5 g 3 times a day). Endoscopic improvement was better with 1.0 g mesalamine 3 times a day than with 0.5 g 3 times a day, but overall endoscopic and histologic improvement was not different between treatment groups. Baseline activity, duration, and localization of ulcerative colitis did have some influence on the therapeutic activity, but there was no significant interaction with the dose of the study drug. Safety, with special focus on kidney function, was excellent in all 3 groups. CONCLUSIONS: There is no significant dose response between mesalamine 1.5 g/day, 3.0 g/day, and 4.5 g/day. The optimal dose to induce remission of ulcerative colitis is 0.5 g 5-aminosalicylic acid 3 times a day. Patients failing with this dose may benefit from an increase of the dose up to 1.0 g 3 times a day, but should also be considered for alternative treatment. A newly developed pellet formulation of 5-aminosalicylic acid has promising efficacy and excellent safety.

Adult↗