Trimebutine Maleate Monotherapy for Functional Dyspepsia: A Multicenter, Randomized, Double-Blind Placebo Controlled Prospective Trial.

Background and Objectives: Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders; it has a great impact on patient quality of life and is difficult to treat satisfactorily. This study evaluates the efficacy and safety of trimebutine maleate (TM) in patients with FD. Materials and Methods: Α multicenter, randomized, double-blind, placebo controlled, prospective study was conducted, including 211 patients with FD. Participants were randomized to receive TM 300 mg twice per day (BID, 108 patients) or placebo BID (103 patients) for 4 weeks. The Glasgow Dyspepsia Severity Score (GDSS) was used to evaluate the relief of dyspepsia symptoms. Moreover, as a pilot secondary endpoint, a substudy (eight participants on TM and eight on placebo) was conducted in to evaluate gastric emptying (GE), estimated using a 99mTc-Tin Colloid Semi Solid Meal Scintigraphy test. Results: Of the 211 patients enrolled, 185 (87.7%) (97 (52.4%) in the TM group and 88 (47.6%) in the placebo group) completed the study and were analyzed. The groups did not differ in their demographic and medical history data. Regarding symptom relief, being the primary endpoint, a statistically significant reduction in GDSS for the TM group was revealed between the first (2-week) and final (4-week) visit (p-value = 0.02). The 99 mTc-Tin Colloid Semi Solid Meal Scintigraphy testing showed that TM significantly accelerated GE obtained at 50 min (median emptying 75.5% in the TM group vs. 66.6% in the placebo group, p = 0.036). Adverse effects of low to moderate severity were reported in 12.3% of the patients on TM. Conclusion: TM monotherapy appears to be an effective and safe approach to treating FD, although the findings presented here warrant further confirmation.

The trimebutine effect on Helicobacter pylori-related gastrointestinal tract and brain disorders: A hypothesis.

The localization of bacterial components and/or metabolites in the central nervous system may elicit neuroinflammation and/or neurodegeneration. Helicobacter pylori (a non-commensal symbiotic gastrointestinal pathogen) infection and its related metabolic syndrome have been implicated in the pathogenesis of gastrointestinal tract and central nervous system disorders, thus medications affecting the nervous system - gastrointestinal tract may shape the potential of Helicobacter pylori infection to trigger these pathologies. Helicobacter pylori associated metabolic syndrome, by impairing gut motility and promoting bacterial overgrowth and translocation, might lead to brain pathologies. Trimebutine maleate is a prokinetic drug that hastens gastric emptying, by inducing the release of gastrointestinal agents such as motilin and gastrin. Likewise, it appears to protect against inflammatory signal pathways, involved in inflammatory disorders including brain pathologies. Trimebutine maleate also acts as an antimicrobial agent and exerts opioid agonist effect. This study aimed to investigate a hypothesis regarding the recent advances in exploring the potential role of gastrointestinal tract microbiota dysbiosis-related metabolic syndrome and Helicobacter pylori in the pathogenesis of gastrointestinal tract and brain diseases. We hereby proposed a possible neuroprotective role for trimebutine maleate by altering the dynamics of the gut-brain axis interaction, thus suggesting an additional effect of trimebutine maleate on Helicobacter pylori eradication regimens against these pathologies.

Familial prevalence of autoimmune disorders in multiple sclerosis in Northern Greece.

OBJECTIVE: The objective of this study was to evaluate for up to 7 years the prevalence of autoimmune disorders among naïve (untreated) multiple sclerosis family members compared with a contemporary general control population in Northern Greece, in a prospective case-control study, and to examine the possible relationship between immunomodulatory treatment and the appearance of additional autoimmune disorders. METHODS: The patients and controls enrolled comprised 1383 patients with definite MS and 4392 relatives in their families and a total of 452 controls families with 1652 members. RESULTS: At baseline, 891 multiple sclerosis families with 3112 members (73 multiplex multiple sclerosis families with 292 members and 818 simplex families with 2820 members) and 355 control families with 1580 members were examined regarding whether they had any of 12 autoimmune diseases. The baseline affected multiplex plus simplex multiple sclerosis families, the family members and the coexistent additional autoimmune disorders were higher compared with controls. There was an increase in longitudinally affected multiple sclerosis families, multiple sclerosis family members and coexistent additional autoimmune disorders compared with respective findings at the baseline observation. Comparison analysis between two time point observations (after a mean 7.1 +/- 2.2 years) for each autoimmune disorder in overall multiple sclerosis family members revealed increased rates for longitudinal autoimmune Hashimoto's thyroiditis, Graves' disease, insulin-dependent diabetes mellitus, psoriasis and vitiligo (p = 0.02, p = 0.006, p = 0.0004, p = 0.05, and p = 0.05, respectively). Some 145 newly developed, longitudinally definite autoimmune cases were recognized in multiplex plus simplex multiple sclerosis families; 116 (80%) of these disorders were observed in patients with multiple sclerosis treated with immunomodulatory medications, and 68 of these 116 (58.6%) cases exhibited baseline positive autoreactive antibodies. Binary logistic regression analysis revealed that immunotherapy predisposes to autoimmunity (odds ratio 2.8, p < 0.001) independently of the presence of baseline autoantibodies and patients' gender. CONCLUSIONS: There is a longitudinally increased frequency of additional autoimmune disorders among multiple sclerosis family members, probably related to immunomodulatory therapy.

Helicobacter pylori infection as a potential risk factor for multiple sclerosis.

Helicobacter pylori infection (Hp-I) has been associated with a wide spectrum of gastrointestinal and extra-digestive manifestations, including neurodegenerative diseases. Contradictory data have been published on Hp-I and multiple sclerosis (MS) association, with studies mainly using serology for Hp-I detection that cannot distinguish between active and past infections. We herein hypothesize that humoral and cellular immune responses induced by active Hp-I, beyond damaging locally the gastric mucosa, they may shape the character of systemic autoimmune responses, contributing to MS pathogenesis. To investigate our hypothesis, active Hp-I has been diagnosed in two small MS Greek cohorts by using primarily gastric mucosa histology. A higher prevalence of active Hp-I was documented in MS patients vs. controls (86.4 vs. 50%, P = 0.002)accompanied by exclusive existence of duodenal ulcer and autoimmune diseases with endoscopic and histological findings of chronic active gastritis for the MS group. Our preliminary data suggested that active Hp-Iunlike other studies, may not protect, but contribute to MS and we proposed possibleHp-relating mechanisms involved in MS pathophysiology, that merit further evaluation.

Increased cerebrospinal fluid Helicobacter pylori antibody in Alzheimer's disease.

BACKGROUND: Helicobacter pylori (H. pylori) infection may play a role in Alzheimer's disease (AD). AIM: A prospective, nonrandomized, comparative study was car- ried out to examine the levels of anti-H. pylori-specific IgG antibodies in the cerebrospinal fluid (CSF) and serum of AD patients, compared with those of age-matched cognitively normal controls. PATIENTS: CSF was aspirated from 27 AD patients and 27 age-matched cognitively normal patients with prostate hyperplasia or long-bone fractures necessitating surgery after epidural anesthesia. Serum samples were obtained from AD patients and the day before surgery from controls. METHODS: CSF and serum anti-H. pylori IgG concentrations were measured by means of an enzyme-linked immunosorbent assay. RESULTS: The mean concentration of anti-H. pylori-specific IgG was significantly greater in (a) the CSF of AD patients (10.53 +/- 12.54 U/mL) than in controls (8.63 +/- 8.01 U/mL, p = 0.047), and (b) the serum of AD patients (30.44 +/- 33.94 U/mL) than in controls (16.24 +/- 5.77 U/mL, p = 0.041). CSF anti-H. pylori IgG antibodies correlated with the degree of severity of the disease. CONCLUSION: H. pylori-specific IgG antibody levels are significantly increased in CSF and serum of AD; its titer in CSF might reflect the AD severity, thereby supporting a role for this common infection in the pathobiology of the disease.

Von Recklinghausen's disease associated with malignant peripheral nerve sheath thmor presenting with constipation and urinary retention: a case report and review of the literature.

A malignant peripheral nerve sheath tumor (MPNST) is a rare neoplasm arising from peripheral nerve sheaths. We herein report the first case of MPNST originating from the left gluteal muscle region, diffusely extending into the adjacent small pelvis and perineum. The patient was a 25-year-old man who presented with symptoms of progressive constipation and urinary retention associated with weight loss. The patient had a family history of neurofibromatosis type 1. Physical examination showed numerous cafe-au-lait spots and sessile cutaneous neurofibromas. A computed tomography scan revealed a giant tumor which displaced the bladder and segments of the intestine. The histopathological diagnosis was MPNST. The mass was considered inoperable and palliative colostomy was performed. The patient declined chemotherapy and radiation therapy and died 2 months later.

Alzheimer's disease and Helicobacter pylori infection: Defective immune regulation and apoptosis as proposed common links.

Although degenerative diseases of the central nervous system, including Alzheimer's disease (AD), have an increasingly high impact on aged population their association with Helicobacter pylori (H. pylori) infection has not as yet been thoroughly researched. Current H. pylori infection appears to induce irregular humoral and cellular immune responses that, owing to the sharing of homologous epitopes (molecular mimicry), cross-react with components of nerves, thereby contributing and possibly perpetuating the apoptotic neural tissue damage observed in neurodegenerative diseases including AD. An association between AD and H. pylori infection has been recently addressed by two studies. A higher seropositivity for anti-H. pylori immunoglobulin G antibodies in 30 patients with AD than in 30 age-matched controls was reported in one study; this serological test, however, has limitations because it does not discriminate between current and old infections. In the other study, by introducing the histological method (the actual gold standard) for diagnosis of H. pylori infection, we reported a higher prevalence of H. pylori infection in 50 AD patients than in 30 anemic controls. This pathogen may influence the pathophysiology of AD by promoting platelet and platelet-leukocyte aggregation; releasing various pro-inflammatory and vasoactive substances; developing cross-mimicry with host antigens; producing reactive oxygen metabolites and circulating lipid peroxides; influencing the apoptotic process; and increasing, through induction of atrophic gastritis, homocysteine, which contributes to vascular disorders implicated in endothelial damage and neurodegeneration.

Efficacy and safety of infliximab in steroid-dependent ulcerative colitis patients.

BACKGROUND/AIMS: Limited data exist concerning infliximab administration in steroid-dependent ulcerative colitis (UC) patients. The aim of this study was to evaluate the efficacy and safety of infliximab in steroid-dependent disease. METHODOLOGY: Sixteen corticosteroid-dependent patients who received infusions of infliximab (5 mg/kg) at 0, 2 and 6 weeks and thereafter every 8 weeks (Group A), were compared with eight patients treated with methylprednisolone (0.8-1 mg/kg body weight) daily for three weeks followed by a tapering regimen up to the minimal dose to maintain a symptom-free condition (Group B). Steroid dependency was defined as recurrent flare-up on steroid reduction or withdrawal, or as the clinical need for steroid treatment twice within six consecutive months or three times within a year. Disease activity was assessed at recruitment, and clinical response was evaluated according to the two non-invasive indices [SEO and Simple Clinical Colitis Activity Index (SCCAI) scores]. RESULTS: In Group A, complete long-term response occurred in 68.75% and partial response in 18.75% of patients. Moreover, in the long-term follow-up, both SCCAI (10.37 +/- 2.27 vs. 3.31 +/- 2.65, p < 0.001) and SEO (209.33 +/- 13.6 vs. 123.3 +/- 34.8, p < 0.001) scores demonstrated a significant improvement. In group B, comparable features were also obtained regarding complete long-term (62.5%) and partial (25%) responses; both SCCAI (7.37 +/- 1.4 vs. 3.5 +/- 3.58, p = 0.039) and SEO (181.0 +/- 27.1 vs. 135.3 +/- 44.1, p = 0.038) scores also improved significantly. Six of eight patients in the methylprednisolone-treated group B developed Cushing-like symptoms. CONCLUSIONS: Infliximab appears to be a good alternative therapeutic regimen in steroid-dependent UC patients associated with long-term potential toxicity.

Relationship between Helicobacter pylori infection and multiple sclerosis.

BACKGROUND: Recent data indicate the presence of immunomodulating properties of Helicobacter pylori (Hp) (Hp Sydney Strain-1 antigen) in an experimental model of multiple sclerosis (MS), and there are limited contradictory epidemiologic data regarding Hp serology in MS patients. METHODS: The aim of this prospective, comparative study was to validate the incidence of active Hp infection by histology and the endoscopic abnormalities, in 44 patients with relapsing-remitting MS and 20 anemic controls. RESULTS: The overall prevalence of histologically confirmed active Hp infection in 44 MS patients was 86.4% vs. 50% in 20 matched anemic control participants (P=0.002, odds ratio 6.33, 95%CI 1.85-21.64). Concomitant diseases of autoimmune origin including hypothyroidism and ulcerative colitis were exclusively present in MS patients. Moreover, a trend of increased presence of pathological endoscopic findings such as hiatus hernia, Barrett's esophagus and duodenal ulcer disease was observed in MS patients compared with controls; Barrett's esophagus and duodenal ulcers were exclusively observed in MS patients. Likewise, Hp (+) MS patients showed exclusive presence of hiatus hernia, esophagitis and duodenal ulcer disease compared with Hp (-) MS patients. CONCLUSION: Hp infection appears to be more frequent in MS patients. If confirmed, this might indicate either a common factor that causes susceptibilities to both MS and Hp infection or that Hp might be a causal factor for developing MS. If a causal link between Hp infection and MS is confirmed in the future, this may have a major impact on the pathophysiology and management of MS.