Small Intestinal Bacterial Overgrowth in Patients with Interstitial Cystitis and Gastrointestinal Symptoms

Purpose Interstitial cystitis (IC) often coexists with irritable bowel syndrome (IBS). IBS may be explained by small-intestinal bacterial overgrowth (SIBO), which increases immune activation and visceral hypersensitivity. This prospective pilot study tested hypotheses that IC patients with gastrointestinal (GI) symptoms have SIBO, that nonabsorbable antibiotic use improves symptoms, and that improvement is sustained by prokinetic therapy. Methods Consecutive IC patients with GI symptoms had lactulose breath testing (LBT). Those with abnormal results received rifaximin 1,200–1,800 mg/day for 10 days then tegaserod 3 mg/nightly. Questionnaires addressed IC and GI global improvement. Results Of 21 patients, 17 (81%) had abnormal LBTs. Of 15 patients treated, GI global improvement was moderate to great in 11 (73%) and sustained in ten (67%). IC global improvement was moderate to great in six (40%) and sustained in seven (47%). Conclusions A majority of IC patients and GI symptoms had an abnormal LBT suggesting SIBO. Rifaximin improved symptoms, which was sustained by tegaserod.     

Is irritable bowel syndrome an infectious disease?

Irritable bowel syndrome (IBS) is the most common of all gastroenterological diseases. While many mechanisms have been postulated to explain its etiology, no single mechanism entirely explains the heterogeneity of symptoms seen with the various phenotypes of the disease. Recent data from both basic and clinical sciences suggest that underlying infectious disease may provide a unifying hypothesis that better explains the overall symptomatology. The presence of small intestinal bowel overgrowth (SIBO) has been documented in patients with IBS and reductions in SIBO as determined by breath testing correlate with IBS symptom improvement in clinical trials. The incidence of new onset IBS symptoms following acute infectious gastroenteritis also suggests an infectious cause. Alterations in microbiota-host interactions may compromise epithelial barrier integrity, immune function, and the development and function of both central and enteric nervous systems explaining alterations in the brain-gut axis. Clinical evidence from treatment trials with both probiotics and antibiotics also support this etiology. Probiotics appear to restore the imbalance in the microflora and improve IBS-specific quality of life. Antibiotic trials with both neomycin and rifaximin show improvement in global IBS symptoms that correlates with breath test normalization in diarrhea-predominant patients. The treatment response to two weeks of rifaximin is sustained for up to ten weeks and comparable results are seen in symptom reduction with retreatment in patients who develop recurrent symptoms.     

Prevalence of Irritable Bowel Syndrome and Depression in Fibromyalgia

The purpose of this study was to determine the point prevalence of depressive symptoms, using the PRIME-MD questionnaire, and irritable bowel syndrome (IBS), while comparing the Rome II to the Rome I criteria, in patients with fibromyalgia (FM) and rheumatologic controls in an outpatient setting. The prevalence of IBS in FM patients (n = 105) was 63% by Rome I and 81% by Rome II criteria. The prevalence of IBS in controls (n = 62) was 15% by Rome I and 24% by Rome II criteria (FM vs. control; P < 0.001). Depressive symptoms were met in 40% of FM patients and 8% of controls (P < 0.001). The coexistence of IBS and depressive symptoms in the FM patients was 31% (Rome I) and 34% (Rome II). The prevalence of IBS and depressive symptoms was higher in FM patients compared to the control population. Identification of IBS and depressive symptoms in FM patients might enable clinicians to better meet the needs of this patient population. The views expressed in this article are those of the authors and do not reflect the official policy or practice of the Department of the Navy, Department of Defense, or the United States Government. This research was performed at outpatient private rheumatology clinics. No financial support was received for the research     

High-dose intravenous immunoglobulin infusion in polyarteritis nodosa

We describe a 58-year-old Japanese female who developed polyarteritis nodosa (PN). Her skin disease and systemic symptoms were resistant to dapsone (1.5 mg kg⁻¹ day⁻¹), high-dose oral prednisone (1 mg kg⁻¹ day⁻¹) and azathioprine (2 mg kg⁻¹ day⁻¹), and intravenous cyclophosphamide pulse therapy (10 mg kg⁻¹ day⁻¹). She was ultimately treated with infusion of high-dose intravenous immunoglobulin (IVIG) at a dose of 0.1 g kg⁻¹ daily for five consecutive days weekly for a period of 12 weeks, resulting in remission of his cutaneous and systemic symptoms and successful tapering of his prednisone and azathioprine dose. However, 12 months later, relapsing fever and polyarthritis recurred, and eventually, 24 months later, indurated erythema and punched-out ulcers appeared on the lower legs. These symptoms were reduced after increasing the dose of oral prednisone (1 mg kg⁻¹ day⁻¹). Our case indicates that the high-dose IVIG infusion therapy may be useful for controlling PN in certain periods since the long-term observation revealed deterioration of symptoms. We review related articles and discuss its effectiveness in PN.     

Breath test for differential diagnosis between small intestinal bacterial overgrowth and irritable bowel disease： An observation on non-absorbable antibiotics

AIM： To estimate the prevalence of small intestine bacterial overgrowth （SIBO） among patients with an earlier diagnosis of irritable bowel disease （IBS） in our geographical area, and to collect information on the use of locally acting non-absorbable antibiotics in the management of SIBO. METHODS： A non-interventional study was conducted in 73 consecutive patients with a symptom-based diagnosis.. RESULTS： When the patients underwent a ＂breath test＂, 33 （45.2%） showed the presence of a SIBO. Arcer treatment with rifaximin 1200 mg/d for seven days in 32 patients, 19 （59.4%） showed a negative ＂breath test＂ one week later as well as a significant reduction of symptoms, thus confirming the relationship between SIBO and many of the symptoms claimed by patients. In the other 13 patients, ＂breath test＂ remained positive, and a further cycle of treatment with ciprofloxacin 500 mg/d was given for 7 additional days, resulting in a negative ＂breath test＂ in one patient only. CONCLUSION： （1） about half of the patients with a symptomatic diagnosis of IBS have actually SIBO, which is responsible for most of the symptoms attributed to IBS; （2） only a ＂breath test＂ with lactulose （or with glucose in subjects with an intolerance to lactose） can provide a differential diagnosis between IBS and SIBO, with almost identical symptoms; and （3） the use of non-absorbable antibiotics may be useful to reduce the degree of SIBO and related symptoms; it must be accompanied, however, by the correction of the wrong alimentary habits underlying SIBO.     

A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence

AIMS: To study the efficacy of rifaximin, a nonabsorbable antibiotic, in relieving chronic functional symptoms of bloating and flatulence. METHODS: Randomized double-blind placebo-controlled trial consisting of three 10-day phases: baseline (phase 1), treatment with rifaximin 400 mg b.i.d. or placebo (phase 2), and post-treatment period (phase 3). Primary efficacy variable was subjective global symptom relief at the end of each phase. A symptom score was calculated from a symptom diary. Lactulose H2-breath test (LHBT) was performed at baseline and end of study. RESULTS: One hundred and twenty-four patients were enrolled (63 rifaximin and 61 placebo). Baseline characteristics were comparable and none had an abnormal baseline LHBT. Rome II criteria were met in 58.7% and 54.1%, respectively. At the end of phase 2, there was a significant difference in global symptom relief with rifaximin versus placebo (41.3% vs 22.9%, p = 0.03). This improvement was maintained at the end of phase 3 (28.6% vs 11.5%, p = 0.02). Mean cumulative and bloating-specific scores dropped significantly in the rifaximin group (p < 0.05). Among patients with IBS, a favorable response to rifaximin was noted (40.5% vs 18.2%; p = 0.04) persisting by the end of phase 3 (27% vs 9.1%; p = 0.05). H2-breath excretion dropped significantly among rifaximin responders and correlated with improvement in bloating and overall symptom scores (p = 0.01). No adverse events were reported. CONCLUSIONS: Rifaximin is a safe and effective treatment for abdominal bloating and flatulence, including in IBS patients. Symptom improvement correlates with reduction in H2-breath excretion. Future trials are needed to examine the efficacy of long-term or cyclic rifaximin in functional colonic disorders.     

Antidepressant Therapy (Imipramine and Citalopram) for Irritable Bowel Syndrome: A Double-Blind,Randomized, Placebo-Controlled Trial

Background The efficacy of antidepressants in irritable bowel syndrome (IBS) is controversial. No trials have directly compared a tricyclic with a selective serotonin reuptake inhibitor. Our aim was to determine whether imipramine and citalopram are efficacious in IBS. Methods This was a randomized, double-blind, placebo-controlled, parallel group pilot trial with imipramine (50 mg) and citalopram (40 mg). Results Of 51 IBS patients randomized, baseline characteristics were comparable among the treatment arms; the majority was diarrhea-predominant. Adequate relief of IBS symptoms (primary endpoint) was similar for each treatment arm. Improvements in bowel symptom severity rating for interference (P = 0.05) and distress (P = 0.02) were greater with imipramine versus placebo, but improvements in abdominal pain were not. There was a greater improvement in depression score (P = 0.08) and in the SF-36 Mental Component Score (P = 0.07), with imipramine. Citalopram was not superior to placebo. Approximately 20% of the variance in scores was explained by treatment differences for abdominal pain, bowel symptom severity disability, depression and the mental component of the SF-36. Conclusion Neither imipramine nor citalopram significantly improved global IBS endpoints over placebo.     

Limited prolonged effects of rifaximin treatment on irritable bowel syndrome-related differences in the fecal microbiome and metabolome

Irritable bowel syndrome (IBS) is a chronic functional disorder and its development may be linked, directly and indirectly, to intestinal dysbiosis. Here we investigated the interactions between IBS symptoms and the gut microbiome, including the relation to rifaximin (1200 mg daily; 11.2 g per a treatment). We recruited 72 patients, including 31 with IBS-D (diarrhea), 11 with IBS-C (constipation), and 30 with IBS-M (mixed constipation and diarrhea) and 30 healthy controls (HCs). Of them, 68%, 64%, and 53% patients with IBS-D, IBS-C, and IBS-M, respectively, achieved 10–12 week-term improvement after the rifaximin treatment. Stool samples were collected before and after the treatment, and fecal microbiotic profiles were analyzed by deep sequencing of 16S rRNA, while stool metabolic profiles were studied by hydrogen 1-nuclear magnetic resonance (¹H-NMR) and gas chromatography–mass spectrometry (GC-MS). Of 26 identified phyla, only Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria were consistently found in all samples. Bacteroidetes was predominant in fecal samples from HCs and IBS-D and IBS-M subjects, whereas Firmicutes was predominant in samples from IBS-C subjects. Species richness, but not community diversity, differentiated all IBS patients from HCs. Metabolic fingerprinting, using NMR spectra, distinguished HCs from all IBS patients. Thirteen metabolites identified by GC-MS differed HCs and IBS patients. However, neither metagenomics nor metabolomics analyses identified significant differences between patients with and without improvement after treatment.     

Rifaximin versus Other Antibiotics in the Primary Treatment and Retreatment of Bacterial Overgrowth in IBS

Purpose Previous studies demonstrate improvement in IBS after antibiotic therapy, with the greatest efficacy seen with the antibiotic, rifaximin. The purpose of this study was to compare the efficacy of rifaximin in both the treatment and retreatment of IBS. Methods A retrospective chart review was conducted on Rome I-positive IBS patients. Charts were reviewed to evaluate all antibiotic treatments (rifaximin, neomycin, doxycycline, amoxicillin/clavulanate, and ciprofloxacin), even those predating 1 July 2004. Data collection included symptoms, breath test results (pre- and post-treatment), antibiotics used, and clinical response to individual antibiotic treatments before and after rifaximin availability in the USA. Results Out of 98 eligible charts, 84 patients received one course of rifaximin. Fifty of these (60%) had a follow-up breath test. Among these, 31 (62%) were clinical responders and 19 (38%) were nonresponders. Of 31 responders, 25 (81%) had a normal follow-up breath test compared with only 3 of the 19 nonresponders (16%) (P < 0.001). Of participants given rifaximin, 69% (58 out of 84) had a clinical response compared with only 38% (9 out of 24) with neomycin (P < 0.01) and 44% (27 out of 61) with all non-rifaximin antibiotics (P < 0.01). Rifaximin was used as retreatment on 16 occasions, and all patients improved. Conclusions Rifaximin is more effective than other antibiotics in the treatment and retreatment of IBS.     

Daunorubicin,cytarabine and fludarabine (DAF) for remission induction in relapsed or refractory acute myeloid leukemia. Evaluation of safety,tolerance and early outcome—Polish Adult Leukemia Group (PALG) pilot study

In 1992–1993, synergistic interaction of ribonucleotide reductase inhibitors (fludarabine, cladribine) and cytarabine (Ara-C) increasing Ara-CTP concentration in myeloblasts was proved. Based on these findings and encouraging results of the addition of cladribine to standard daunorubicin+Ara-C induction regimen (DAC) in acute myeloid leukemia (AML), the Polish Adult Leukemia Group (PALG) conducted a pilot study on the administration of cytarabine, daunorubicin, and fludarabine (DAF) as a reinduction treatment of AML to assess tolerance, toxicity, and early outcome. The DAF regimen consisted of daunorubicine 60 mg m⁻² day⁻¹ iv on days 1–3 and fludarabine 25 mg m⁻² day⁻¹ iv on days 1–5 given before cytarabine 200 mg m⁻² day⁻¹ in ci on days 1–7. Thirty-four AML patients with median age 39, 24% relapsed and 76% refractory, were included into the study between September 2003 and August 2004. Achieved response rate in the whole study population was 56%; n = 16 patients with complete remission (CR), and n = 3 patients with partial remission (PR). Fifteen of 16 patients achieved CR after the first course of therapy. Only 9% of total population died before the assessment of remission. All patients developed severe neutropenia. Serious infections were observed in 47% of the cases. Severe thrombocytopenia was observed in 72% of the patients. All patients required substitution of platelet concentrates (median 4), and PRBC (median 5). Severe alopecia, mucositis, vomiting were of low frequency. Liver, kidney, or circulatory failure, diarrhea, or polyneuropathy were not observed. The probability of overall survival (OS) for 1 year for the whole study population (34 patients) and the group of 16 patients in CR was: 44% (95% confidence interval [CI] 36–52%) and 69% (95% CI 55–83%), respectively. The probability of leukemia-free survival (LFS) for 1 year was 38% (95% CI 22–54%). Summarizing, DAF regimen used as the induction therapy in relapsed/refractory AML was well tolerated with acceptable toxicity and early efficacy.     

Correlation between Restless Leg Syndrome and Superficial Venous Reflux

Restless leg syndrome (RLS) is a common cause of lower extremity discomfort. We hypothesized that patients with RLS symptoms have higher rates of deep and superficial venous reflux (SVR). Retrospective review of patients ≥18 years of age evaluated in a venous center from December 2018 to February 2019. Differences in rates of RLS symptoms, demographics, comorbidities, and clinical and radiologic presence of venous disease were analyzed. Overall, 207 patients were analyzed; 140 (67.6%) reported RLS symptoms ( n  = 25 with prior RLS diagnosis). RLS symptoms were more common with superficial or combined superficial and deep venous reflux (DVR) compared with those without reflux ( p  < 0.001). Patients with RLS symptoms as opposed to those without had similar demographics and comorbidities (all p  > 0.05) but increased rates of venous pain, phlebitis, family history of venous disease, lower extremity swelling and SVR, and combined SVR and DVR (all p  < 0.05). Our multivariable logistic regression found presence of SVR, and family history of venous reflux was associated with RLS symptomatology (all p  < 0.001). Ninety-nine patients with RLS underwent ablation; of them, 93 had duplex-proven reflux resolution of which 81 (87%) reported RLS symptom improvement. This included 13 of 16 (81.3%) with prior RLS diagnosis. SVR is associated with increased rates of RLS symptoms in a vein center population. Therefore, RLS symptoms should trigger a targeted venous evaluation. Our results suggest that venous ablation may lead to resolution of RLS symptoms in patients with SVR, but randomized prospective trials with strict RLS definition criteria are warranted to confirm these outcomes.     

Study confirms benefit of surgery for gastroesophageal reflux disease

Evaluation of: Pimentel M, Lembo A, Chey WD et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N. Engl. J. Med. 364(1), 22–32 (2011).

Alterations in gut flora may play an important role in the pathophysiology of bowel symptoms, especially in patients with irritable bowel syndrome (IBS). If so, antibiotics that affect gut flora may offer a novel approach for the management of patients with IBS. Here, we discuss the results of two identically designed, double-blind, placebo-controlled trials (TARGET 1 and TARGET 2) of a poorly absorbed antibiotic, rifaximin, in patients with IBS. In these studies, 1260 patients (females 76.1 and 72.1%, respectively) who had IBS without constipation were randomized to receive either rifaximin 550 mg or placebo, three-times daily for 2 weeks. Subsequently, daily symptoms were assessed and patients were followed up for 10 weeks. The primary outcome measure – adequate relief of global IBS symptoms during the first 4 weeks after treatment – was met in significantly more patients who received rifaximin than placebo (p < 0.001). In addition, more patients in the rifaximin group than in the placebo group (p < 0.001) reported an adequate relief of bloating, and an improvement in abdominal pain and stool consistency – secondary outcome measures. The incidence of adverse events with rifaximin was similar to placebo, and the drug was well tolerated. In summary, a 2-week course of rifaximin provided significant relief of IBS symptoms, as well as bloating and abdominal pain.     

Evolution of Visceral Sensitivity in Patients with Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) has been associated with visceral hypersensitivity. Here we examined the evolution of rectal sensitivity and of gastrointestinal symptomatology in IBS patients over time, to verify if the clinical and biological parameters showed parallel behavior. Patients complaining of IBS, identified by Rome 1 criteria, were included in this study. The severity of the gastrointestinal (Gastrointestinal) symptoms was assessed by a gastrointestinal index. The pain threshold to rectal distension was measured by a barostat programmed for phasic ascending distensions. Both measures were obtained before and after treatment. Thirty-nine patients were followed while on a 10-week group psychotherapy (psy) program. Twelve patients were controlled after pharmacological treatment with amitriptyline (Ami) 10 mg hours for two weeks and then 25 mg hours for the following 4 weeks. Clinical improvement with symptom reduction was achieved in both patients groups. With psy, the Gastrointestinal index declined from an initial value of 78.4 ± 4.8 to 65.5 ± 4.5 at the end of treatment (P < 0.05). With Ami, the gastrointestinal index decreased from 91.6 ± 5.6 to 61.8 ± 9.1 (p < 0.01). The pain threshold to rectal distension increased from 27.7 ± 1.0 to 33.7 ± 1.9 mmHg (P < 0.01) after drug treatment, but remained unchanged (30.6 ± 1.0 vs 30.6 ± 1.1 mm Hg) with psy. Evolution of the gastrointestinal index and rectal sensitivity were directly correlated (r = –0.71; P < 0.01) in Ami patients, but not in those treated with Psy (r = –0.001). In conclusion, visceral hypersensitivity appeared as a stable biological defect over a 10- to 12-week period during clinically-effective treatment with psychotherapy. Rectal pain threshold, however, seemed to be pharmacologically manipulatable in patients treated with Ami.     

Patients treated by tegaserod for irritable bowel syndrome with constipation showed significant improvement in fibromyalgia symptoms. A pilot study

The symptoms of irritable bowel syndrome (IBS) are commonly seen in fibromyalgia (FM) patients. This study aimed to evaluate the effect of 5-hydroxytryptamin-4 receptor partial agonist (tegaserod) on the symptoms of FM among the patients who receive the medicine because of IBS. Forty-one female patients with IBS and constipation, which were subjects to tegaserod treatment, were examined by rheumatologist and 14 were found to suffer from FM. The fibromyalgia impact questionnaire (FIQ) and clinical examination were done before tegaserod treatment and 1 month after. The IBS status, the total FIQ score, the number of tender points and pain in tender points were lowered significantly after the treatment (p < 0.001 for all variables). The results of this pilot study provide the preliminary evidence that FM patients can benefit from treatment by 5-hydroxytryptamin-4 receptor partial agonist. Additional studies are needed to support this conclusion.     

Bronchial Hyperresponsiveness in Irritable Bowel Syndrome

Extraintestinal symptoms are often found in patients with irritable bowel syndrome (IBS). Recent studies suggest that IBS is associated with bronchial hyperresponsiveness. But it is still arguable that the bronchial hyperresponsiveness is associated with IBS patients. The purpose of this study is to investigate the possible relationship between IBS and bronchial hyperresponsiveness. Forty-two patients with IBS and 42 control subjects were included in this study. All patients underwent pulmonary function, methacholine challenge, and skin prick tests. There was no statistical difference between the two groups with respect to percentage of all pulmonary function test parameters, including FEV₁%, FCV%, FVC/FEV₁, and FEF_{25 − 75}%. Only two persons in the alternating-type IBS patient group and one person in the control group tested positive in the methacholine provocation test. But all PC₂₀ values were above 16 mg/ml. These results do not demonstrate a relationship between bronchial hyperresponsiveness and IBS. However, a relationship might exist in a subpopulation of IBS patients.     

Symptom Provocation in Irritable Bowel Syndrome Effects of Differing Doses of Fructose-Sorbitol

The role of fructose and sorbitol, when ingested together, in the aetiology of irritable bowel syndrome (IBS) is controversial. The aims of this study in IBS patients, therefore, were to compare differences in symptom provocation with various doses of fructose-sorbitol and to relate differences in the extent of colonic hydrogen production after each dose to such symptom provocation. Two different mixtures of fructose and sorbitol-20 g fructose plus 3.5 g sorbitol ('lower' dose) and 25 g fructose plus 5 g sorbitol (‘higher’ dose)-were administered to 15 patients with IBS and to 24 healthy controls. Breath hydrogen concentrations were determined at 10-min intervals for 3 h after ingestion of each mixture, and the presence and severity of a range of gastrointestinal symptoms were recorded on a standard form before, during, and after the study. Total symptom score in IBS patients, but not controls, was greater (p > 0.05) after the higher than after the lower dose of fructose-sorbitol mixture, and, for the higher dose, symptoms were significantly greater in IBS patients than in controls (p > 0.05). Moreover, the increase in total symptom score between the higher and lower dose mixtures was of a greater magnitude (p = 0.01) in IBS patients than in controls. No significant correlation was observed between the increase in symptom score and the increase in peak hydrogen concentration or the increase in integrated hydrogen response between lower and higher dose mixtures, although these latter increases were at times substantial. We conclude that in patients with IBS who ingest fructose and sorbitol simultaneously, the degree of symptom provocation is related to the amounts present in such a mixture but is not related directly to the extent of colonic hydrogen production.     

Functional Gastrointestinal Disorders in Unselected Patients with Non-Cardiac Chest Pain

Patients with non-cardiac chest pain (NCCP) (n = 387) and cardiac chest pain (CCP) (n = 93) were compared with community controls (n = 81), using a symptom questionnaire that assessed the presence of irritable bowel syndrome (IBS), functional dyspepsia, and oesophageal dysfunction and chest pain characteristics. A significantly (p < 0.05) increased prevalence of symptoms compatible with IBS occurred in NCCP patients when compared with those with CCP and with controls. Dysphagia was more frequent in both those with non-cardiac and cardiac chest pain than in controls; this was not apparent, however, when patients with concomitant IBS were excluded. The presence of oesophageal or gastrointestinal symptoms did not enable discrimination with regard to the chest pain characteristics. We conclude that unselected referred patients with documented NCCP are more likely to have IBS and that the presence of oesophageal symptoms such as dysphagia may merely reflect the spectrum of the ‘irritable gut’.     

Efficacy of rifaximin, a nonabsorbed oral antibiotic, in the treatment of small intestinal bacterial overgrowth

INTRODUCTION: Rifamixin is an orally administrated, nonabsorbed antibiotic whose utility in eradication of small intestinal bacterial overgrowth (SIBO) is currently being evaluated. PURPOSE: The aim of this study was to investigate efficacy and safety of rifaximin in relieving symptoms and normalizing the glucose breath test (GBT) in patients with SIBO. METHODS: Symptom score assessment, consisting of frequency and severity of bloating, gas, abdominal pain, and bowel movements and the GBT were performed before and after treatment with rifaximin 800 mg/d for 4 weeks. SUBJECTS: Twenty consecutive symptomatic patients (16 women and 4 men; mean age, 47.8 years; range, 19 to 85 years) who had a positive GBT were prospectively studied in an open-labeled fashion. Fourteen patients (70.0%) presented with diarrhea, 3 (15.0%) with bloating and gas, and 3 (15.0%) with constipation as the dominant symptom. RESULTS:: Eleven patients were hydrogen producers, 8 exclusively methane, and 1 patient produced both gases by the GBT. Among patients with diarrhea, 12 of 14 (85.7%) reported improvement in symptom scores of more than 50%; 1 between 25% and 50%, 1 had no response after 4 weeks of rifamixin. Among patients with bloating and gas or constipation as the main symptom: 2 of 6 (33.3%) had improvement between 50% and 75%; 3 (50%) had 25% to 50% improvement, and 1 (16.7%) had no response. Repeat GBT at the end of the 4 weeks showed that 54.5% of hydrogen formers and 50.0% of methane producers were eradicated, and there was a significant reduction (P <0.05) in the area under the concentration-time curve and peak values. No adverse effects were observed. CONCLUSIONS: Rifaximin in a dose of 800 mg per day for 4 weeks: 1) was safe and effective treatment in reducing symptoms in patients with SIBO of multiple etiologies, especially when diarrhea was the dominant symptom; and 2) normalized the GBT in approximately 50% of patients. Data support a future therapeutic role for rifaximin in SIBO.     

The Effect of the Phytoestrogen Genistein on Myocardial Protection, Preconditioning and Oxidative Stress

Introduction We have previously shown that estrogen administered in ovariectomized female rabbits significantly reduce myocardial infarct size. We now investigated whether the phytoestrogen genistein similarly protects ischemic myocardium and whether this is associated with its antioxidant properties. In addition, we examined whether genistein abolishes preconditioning, since at high doses, it inhibits tyrosine kinase. Materials and methods We studied five groups of New Zealand white female rabbits. Group A (n = 12) were normal controls, group B (n = 14) were ovariectomized 4 weeks prior to the experiment, group C (n = 10) were ovariectomized and treated with genistein (0.2 mg kg⁻¹ day⁻¹ subcutaneously) for 4 weeks before the experiment, group D (n = 12) had intact gonads and were treated with genistein (0.2 mg kg⁻¹ day⁻¹ subcutaneously) for 4 weeks before the experiment and group E (n = 8) were ovariectomized 4 weeks prior to the experiment and treated with a single dose of genistein (0.2 mg kg⁻¹ day⁻¹ subcutaneously) just prior to the experiment. All animals underwent 30 min of heart ischemia and 120 min of reperfusion, with (subgroup I) or without (subgroup II) preconditioning. Malondialdehyde (MDA) concentration just before the experiment was determined. Results We found significant differences between the groups—p < 0.0001 in factorial ANOVA. The groups with preconditioning had significant smaller infarcts compared to those without—AI vs AII (10.66 ± 1.42% vs 43.22 ± 2.67%), BI vs BII (18.53 ± 2.36% vs 43.05 ± 8.37%), CI vs CII (10.17 ± 2.07% vs 44.5 ± 5.47%), DI vs DII (14.98 ± 2.36% vs 37.79 ± 3.92%) and EI vs EII (17.11 ± 3.24% vs 42.08 ± 3.42%), p < 0.0005. Ovariectomy was not associated with larger myocardial infarctions—AII vs BII, p = NS. Genistein, for 4 weeks, did not protect ischemic myocardium in either ovariectomized or non-ovariectomized animals—BII vs CII and AII vs DII, p = NS. There was no significant difference between the preconditioned animals, with intact gonads or ovariectomized (AI vs BI, p = NS), ovariectomized with or without genistein (BI vs CI, p = NS) and non-ovariectomized whether treated with genistein or not (AI vs DI, p = NS). A single dose of genistein did not offer any protection (EII vs BII, p = NS), nor did it modify the preconditioning effect (EI vs BI, p = NS). We found no significant difference in MDA plasma levels between the groups. Conclusion Genistein, at this dose, does not reduce infarct size per se nor abolishes the protection induced by preconditioning, in both ovariectomized and non-ovariectomized animals. Preconditioning offers myocardial protection in animals with intact gonads as well as estrogen deprived; bilateral ovariectomy, at least during short-term, is not associated with larger myocardial infarcts compared to control animals. In addition estrogen deprivation, during short term, as well as genistein do not modify oxidative stress.     

Antibiotic Treatment of Constipation-Predominant Irritable Bowel Syndrome

Background

The antibiotic rifaximin is used to treat non-constipated irritable bowel syndrome (IBS). Methane production is associated with constipation and its severity in constipation-predominant IBS (C-IBS). A previous retrospective study suggested that rifaximin and neomycin was superior to neomycin alone in improving symptoms in methane-positive subjects.

Aims

To determine the effectiveness of neomycin alone or with rifaximin in improving symptoms in methane-positive C-IBS subjects.

Methods

A double-blind, randomized, placebo-controlled trial was performed from 2010 to 2013 at three tertiary care centers. Subjects aged 18–65 with C-IBS (Rome II criteria) and breath methane (>3 ppm) meeting the inclusion and exclusion criteria were recruited. Subjects completed a baseline symptom questionnaire rating the severity of abdominal and bowel symptoms on a visual analog scale and were randomized to receive neomycin and placebo or neomycin and rifaximin for 14 days. Symptom severity was assessed by weekly questionnaire for 2 weeks of therapy and 4 additional weeks of follow-up.

Results

Thirty-one subjects (16 neomycin and placebo, 15 neomycin and rifaximin) were included in the intention-to-treat analysis. Constipation severity was significantly lower in the neomycin and rifaximin group (28.6 ± 30.8) compared to neomycin alone (61.2 ± 24.1) (P = 0.0042), with greater improvement in constipation (P = 0.007), straining (P = 0.017) and bloating (P = 0.020), but not abdominal pain. In the neomycin and rifaximin group, subjects with methane <3 ppm after treatment reported significantly lower constipation severity (30.5 ± 21.8) than subjects with persistent methane (67.2 ± 32.1) (P = 0.020).

Conclusions

Rifaximin plus neomycin is superior to neomycin alone in improving multiple C-IBS symptoms. This effect is predicted by a reduction in breath methane.