Can nausea and vomiting be treated with ginger extract?

Ginger (Zingiber officinale) is a spice traditionally used to treat indigestion, nausea and vomiting. Ginger extracts accelerate gastric emptying and stimulate gastric antral contractions. These effects are mainly due to the presence of gingerols and shogaols and their activity on cholinergic M receptors and serotonergic 5-HT and 5-HT receptors. Various researches on this subject have led to controversial results, due to the chemical instability of ginger extracts and particularly of gingerols, which are readily-oxidizable substances. A systematic review of double-blind, placebo-controlled, randomized studies highlighted the potential efficacy of ginger on the prevention and treatment of nausea and vomiting of various origins, even though additional controlled studies are needed. This review focuses on pregnancy-induced nausea and vomiting and on chemotherapy induced nausea, and hypothesizes a therapeutic role for ginger extracts in case of side effects, as an alternative to traditional prokinetic drugs such as domperidone, levosulpiride or metoclopramide.

Immunomodulatory effects of 1,25-dihydroxyvitamin D3 on TH1/TH2 cytokines in inflammatory bowel disease: an in vitro study.

Crohn's disease (CD) is associated with a higher type-1-helper T cell (Th1) cytokine expression, whereas ulcerative colitis (UC) appears to express a modified Th2 response. In addition to its classic role in calcium homeostasis, calcitriol, the hormonal active form of vitamin D, exerts immunoregulatory effects such as modulation of Th1/Th2 cytokines. Therefore, calcitriol administration could modify immune dysfunction in CD and UC. Nine patients with UC (M/F: 5/4; mean age 47 years, remission(R)/active(A) disease: 7/2), 8 patients with CD (M/F: 2/6; mean age 36, R/A 5/3) and 6 healthy controls (HC) (M/F: 3/3, mean age 4) were enrolled. Peripheral blood was collected after a drug-washout of 15 days and peripheral blood mononuclear cells were stimulated with mitogens alone or in the presence of physiological concentrations of calcitriol (100 pg/ml). Type 1 (IL-2, TNF-alpha, IFN-gamma) and type 2 (IL-10) cytokine production was assayed on supernatants by ELISA. Compared to HC, TNF-alpha production was significantly higher both in UC (p=0.0002) and CD (p=0.0001) patients, at baseline and after incubation with calcitriol (UC p=0.0003, CD p=0.0009). The effects of calcitriol incubation were: 1) reduced IFN-gamma (p=0.024) and increased IL-10 (p=0.06) production in UC patients; 2) reduced TNF-alpha production in CD (p=0.032); 3) no significant effects in HC. Calcitriol increased, albeit not significantly, IL-10 production in UC compared to CD patients (p=0.09). These results suggest an important modulatory role of vitamin D in the Th1/Th2 immune response. The observation that the effect of this modulation was different in CD compared to UC patients provides an interesting area of research into the pathogenesis and treatment of these inflammatory conditions.

Use of colonoscopy in the management of patients with Crohn's disease: appropriateness and diagnostic yield.

INTRODUCTION: Colonoscopy is a necessary tool in the management of Crohn's disease, but the benefit achieved by the procedure is a matter of debate. In the present study we evaluate the clinical impact of performing colonoscopy in Crohn's disease patients. METHODS: Consecutive patients with Crohn's disease undergoing colonoscopy were considered. The following issues were considered: appropriateness of indications; relevant findings able to change the management of the patients; the endoscopist's management decisions based on patient's clinical picture, i.e. increased, maintained or decreased treatment, compared with those selected after performing endoscopy. RESULTS: 204 patients (116 male/88 female, mean age 41 years) were included. Colonoscopy was judged indicated in 52.9% cases, according to current guidelines. In 54% of patients, endoscopy revealed a significant lesion, and this rate was significantly lower for non-indicated procedures (25.9%, p<0.0001). The endoscopic findings were in disagreement with symptoms in about 25% of cases, but the impact of the endoscopic findings on the endoscopist's decision was likely to be very small without any differences between appropriate and inappropriate procedures. CONCLUSIONS: Endoscopy is a potent tool in the management of Crohn's disease, if correctly used, but in the majority of cases a correct therapeutic decision may be established simply on the basis of clinical picture and non-invasive markers, whilst relevant endoscopic findings have a relatively low impact on the medical treatment.

Systematic review: gastro-oesophageal reflux disease and dental lesions.

BACKGROUND: Dental erosion (DE), which is the irreversible loss of tooth substance that does not involve bacteria ranging from a minimal loss of surface enamel to the partial or complete exposure of dentine by a chemical process, is acknowledged as an established extra-oesophageal manifestation of gastro-oesophageal reflux disease (GERD). However, the real impact of GERD in the genesis of this lesion remains unclear. AIM: To review the existing literature to assess the relationship between DE and GERD. METHODS: Studies that assessed the prevalence of DE in individuals with GERD or vice versa were identified in Medline and the Cochrane Controlled Trials Register via a systematic research strategy. RESULTS: Seventeen studies met the selection criteria. Studies, however, differed greatly as far as design, population methods of diagnosing GERD, duration of follow-up and, consequently, findings. The median prevalence of DE in GERD patients was 24%, with a large range (5-47.5%), and the median prevalence of GERD in DE adults patients was 32.5% (range: 21-83%) and in paediatric population 17% (range: 14-87%). Children with GERD are found by a majority of studies at increased risk of developing DEs in comparison with healthy subjects, as are intellectually disabled people. CONCLUSIONS: This systematic review shows that there is a strong association between GERD and DE. The severity of DEs seems to be correlated with the presence of GERD symptoms, and also, at least in adults, with the severity of proximal oesophageal or oral exposure to an acidic pH. The inspection of the oral cavity in search for DEs should become a routine manoeuvre in patients with GERD.

Effects of intramural administration of Botulinum Toxin A on gastric emptying and eating capacity in obese patients.

BACKGROUND: Intraparietal gastric administration of Botulinum Toxin A has been studied in open trials to induce satiety and increase weight loss of obese patients with contradictory results. In previous studies only the antrum was the target for Botulinum Toxin A, whereas the fundus, which exerts important activity on gastric accommodation, was excluded. In this study we report the effects of injection into both gastric regions on solid gastric capacity and emptying of the stomach. MATERIALS AND METHODS: In this study we extended our previous investigations to include 30 obese patients who received Botulinum Toxin A (120 U into the antrum and 80 U into the fundus) or saline by intraparietal endoscopic injection. The two groups were homogeneous for age, gender, body weight and body mass index. Body weight and body mass index, solid gastric emptying (T(1/2) and T(lag) at the octanoic acid breath test) and maximal gastric capacity for solids (kcal) were determined before injection and 2 months later. The results were expressed as mean values (S.E.M.). t-Test or Wilcoxon test was used for statistical analysis, p<0.05 being considered significant. RESULTS: Both treatments induced a significant reduction of body weight and body mass index but Botulinum Toxin A exerted a significantly greater effect (body weight -11.8+/-0.9 kg vs. -5.5+/-1.1 kg, p<0.0002; body mass index -4.1+/-0.2 vs. -2.2+/-0.4, p<0.001). The maximal gastric capacity for solids was also reduced by both Botulinum Toxin A and placebo, the former being significantly more effective (679+/-114 kcal vs. 237+/-94 kcal, p<0.008). Botulinum Toxin A also significantly increased T(1/2) from 83.4+/-3.9 to 101.6+/-9.9 min, p<0.03) but T(lag) was unchanged. Placebo had no effect on either of these parameters. CONCLUSIONS: Our results demonstrated that Botulinum Toxin A makes weight loss easier in obese patients. It acts by increasing the solid gastric emptying time and reducing the solid eating capacity of the stomach.

Assessment of gastro-oesophageal reflux symptoms in Italian physicians -- a survey by Reflux Disease Questionnaire.

BACKGROUND: The prevalence of gastro-oesophageal reflux disease symptoms in physicians, as compared to that of the general population, is not known. METHODS: We submitted a validated Italian version of a simple questionnaire (Reflux Disease Questionnaire) to 490 physicians and 430 controls to assess: (i) the presence, frequency and severity of gastro-oesophageal reflux disease symptoms in the two populations; (ii) how the self-assessment of troublesome gastro-oesophageal reflux disease symptoms by physicians correlate with a pathological Reflux Disease Questionnaire, judged on the basis of a total Reflux Disease Questionnaire score >or=8. RESULTS: A valid and complete questionnaire was obtained in 456/490 (93.1%) physicians and 367/430 (85.3%) controls. Between the two groups there were no differences in terms of total Reflux Disease Questionnaire score or individual items, with the only exception of "severity of burning feeling behind breastbone" which was significantly higher in the physician group. An excellent correlation was found between the self-assessment by physician and the total Reflux Disease Questionnaire score. CONCLUSIONS: The prevalence of gastro-oesophageal reflux disease symptoms among Italian doctors is not different from that reported by a matched control group, and that their ability in self-assessing a troublesome gastro-oesophageal reflux disease is optimal.

The lessons learned from randomized clinical trials of GERD.

Despite the huge number of randomized controlled clinical trials published on gastro-oesophageal reflux disease, the translation of the information gathered into clinical practice is rather limited. The aim of this article is to summarize the results of pivotal randomized controlled clinical trials and review articles on reflux disease and evaluate to what extent their results can be applied to current clinical practice. We reviewed the most relevant randomized controlled clinical trials and reviews since the publication of the first randomized controlled clinical trial on reflux oesophagitis (1978) to date. Six areas were explored, namely: (1) diagnostic "entry" criteria, (2) efficacy parameters, (3) duration of therapy, (4) degree of antisecretory effect, (5) placebo effect, (6) follow-up data. Gastro-oesophageal reflux disease is now the most frequent upper GI disorder treated by gastroenterologists in Europe and North America. There is still a dearth of information regarding the natural history of the disease. The types of information generated through randomized controlled clinical trials have had only limited applicability to routine clinical practice. In the future, large cooperative databases accumulating the clinical histories of a great variety of gastro-oesophageal reflux disease patients may help to provide us with the much needed insights into the natural history of this common disorder.

Review article: the management of steroid dependency in ulcerative colitis.

BACKGROUND: Approximately 20% of patients with ulcerative colitis have a chronic active disease often requiring several courses of systemic steroids in order to achieve remission, but followed by relapse of symptoms during steroid tapering or soon after their discontinuation. Although short term control of symptoms can be achieved with steroid treatment, this pattern of drug response, known as steroid-dependency, leads to important complications of the treatment, while a significant proportion of patients requires colectomy. AIM: To review the studies currently available specifically evaluating the management of steroid-dependent ulcerative colitis. RESULTS: The clinical and biological mechanisms of steroid-dependency are not well understood compared with those determining steroid-refractoriness. Very few evidence-based data are available concerning the management of patients with steroid-dependent ulcerative colitis. The therapeutic role of aminosalicylates, thiopurines, methotrexate, infliximab, leukocyte apheresis and other drugs in the treatment of steroid-dependent ulcerative colitis are evaluated. CONCLUSIONS: Outcomes of studies in steroid-refractory patients may not be applicable to steroid-dependency. Trials are needed to define the correct approaches and new strategies to ameliorate the therapy of steroid-dependent ulcerative colitis.

Transient small-bowel intussusceptions in adults: significance of ultrasonographic detection.

AIM: To investigate the frequency, clinical significance, and outcome of small-bowel intussusceptions in adults detected using ultrasound in an outpatient setting. PATIENTS AND METHODS: In two different retrospective (January 2001 to April 2003) and prospective (May 2003 to June 2005) periods, 33 small-bowel intussusceptions were found in 32 patients (13 females; mean age: 38.1 years) with known or suspected intestinal disease. Patients underwent diagnostic work-up to assess any organic disease. Patients with self-limiting intussusception were submitted to clinical and ultrasonographic follow-up. RESULTS: Of the 32 patients with small-bowel intussusception, 25 were identified in the prospective series of 4487 examinations (0.53%) and seven in the retrospective series of 5342 examinations (0.15%; p=0.002). Four patients had persistent and 28 self-limiting intussusceptions. Self-limiting intussusceptions were idiopathic in 11 patients (39%) or associated with organic diseases in 17 (Crohn's disease in 11 patients, celiac disease in three, ulcerative colitis in one patient, and previous surgery for cancer in two). Self-limiting intussusceptions were asymptomatic in 25% of patients. CONCLUSION: Small-bowel intussusceptions in adults are not rare and are frequently self-limiting, idiopathic, or related to organic diseases, mainly Crohn's disease and coeliac disease.

COXIBs and non-selective NSAIDs in the gastroenterological setting: what should patients and physicians do?

Although adverse effects of nonsteroidal anti-inflammatory drugs occur in only a small proportion of users, the widespread use of these drugs has resulted in a substantial overall number of affected persons who experience serious gastrointestinal complications. Dyspeptic symptoms are estimated to occur in 10-60% of nonsteroidal anti-inflammatory drug users and lead to discontinuation of treatment in 5-15% of rheumatoid arthritis patients taking nonsteroidal anti-inflammatory drugs. It is now well established that the point prevalence of peptic ulcer disease in patients receiving conventional nonsteroidal anti-inflammatory drug therapy ranges between 10 and 30%, representing a 10- to 30-fold increase over that found in the general population. One out of 175 users of conventional nonsteroidal anti-inflammatory drugs in the USA will be hospitalized each year for nonsteroidal anti-inflammatory drug-induced gastrointestinal damage. The mortality of hospitalized patients remains about 5-10%, with an expected annual death rate of 0.08%. The selective COX-2 inhibitors consistently show comparable efficacy to that of conventional nonsteroidal anti-inflammatory drugs in patients with rheumatoid arthritis and osteoarthritis, but have a reduced propensity to cause gastrointestinal toxicity. In many cases, the gastric effects of therapeutically active doses of COX-2 inhibitors are indistinguishable from placebo. The safety benefits of COX-2 inhibitors given alone appear similar to those of combined therapy with conventional nonsteroidal anti-inflammatory drugs and gastroprotective agents. These findings warrant the consideration of COX-2 inhibitors as first-line therapy in patients requiring long-term pain control.

Multidrug resistance 1 gene polymorphism and susceptibility to inflammatory bowel disease.

BACKGROUND: Several studies have evaluated the role of the multidrug resistance 1 gene (MDR1) polymorphism, which encodes the membrane-bound efflux transporter P-glycoprotein 170, in determining susceptibility to and disease behavior in inflammatory bowel disease (IBD), but with conflicting results. METHODS: A total of 211 patients with Crohn's disease (CD), 97 patients with ulcerative colitis (UC), and 212 control subjects were investigated for the presence of MDR1 G2677T/A and C3435T polymorphisms. Genotype frequencies of CD and UC patients were compared to those observed in a control population. Genotype-phenotype correlations with major clinical features were also established and estimated risks (odds ratio [OR] with 95% confidence interval [CI]) for the mutations were calculated by a logistic regression analysis and multiple correspondent analysis. RESULTS: No significant difference was observed for genotype frequencies for both MDR1 G2677T/A and C3435T polymorphisms on overall disease susceptibility for either CD or UC patients compared with control subjects. A significant association was found between the MDR1 C3435T polymorphism and patients with ileo-colonic CD (OR = 3.34; 95% CI: 1.34-8.27). Interestingly, a negative association was found between MDR1 C3435T polymorphism in patients with a positive family history for IBD (OR = 0.44; 95% CI: 0.20-0.95) and articular manifestations (OR = 0.29; 95% CI: 0.13-0.68). Both susceptible and protective effects were identified. No significant association between G2677T/A polymorphism and any specific subphenotypes was found, nor was there any association with subphenotypic categories of UC and both single nucleotide polymorphisms. CONCLUSIONS: The results of our study suggest that MDR1 gene polymorphism could have a role in determining susceptibility to IBD. The variability of this possible effect in the several studies reported so far may be the indirect expression of the complex role played by the MDR1 gene and its product, P-glycoprotein 170, in the regulation of host-bacteria interactions and in the pathogenesis of IBD.

Treatment of morbid obesity by intraparietogastric administration of botulinum toxin: a randomized, double-blind, controlled study.

OBJECTIVE: The stomach is the main target organ for bariatric surgery, but no medical treatment has been developed to increase satiety and decrease food intake via gastric pathways. The aim of our study was to investigate whether or not the intraparietogastric administration of botulinum toxin A (BTX), able to modify the motility patterns of the stomach, could be useful for treatment of obesity. DESIGN: Double blind controlled study. SUBJECTS: Twenty-four morbidly obese patients (mean weight (s.e.m.) 116.1+/-4.89 kg, mean body mass index (BMI) 43.6+/-1.09 kg/m(2)) were blindly randomized to receive 200 IU BTX or placebo into the antrum and fundus of the stomach by intraparietal endoscopic administration. MEASUREMENTS: We evaluated weight loss, BMI changes, satiety score, the maximal gastric capacity for liquids and the gastric emptying time (octanoic acid breath test). RESULTS: The two groups were homogeneous for anthropometric characteristics. Eight weeks after treatment, BTX patients had significantly higher weight loss (11+/-1.09 vs 5.7+/-1.1 kg, P<0.001) and BMI reduction (4+/-0.36 vs 2+/-0.58 kg/m(2), P<0.001) and a higher satiety score on a visual analogic scale (7.63+/-0.38 vs 4.72+/-0.44, P<0.001) than controls. Furthermore, BTX patients showed a significantly greater reduction in maximal gastric capacity for liquids (266.6+/-48 vs 139+/-31, P<0.001) and a greater prolongation in gastric emptying time (+18.93+/-8 vs -2.2+/-6.9 min, P<0.05). No significant side effects or neurophysiologic changes were found. CONCLUSIONS: Topical intragastric BTX was effective in reducing food intake and body weight in morbidly obese patients.

Pretreatment endoscopy--pro & contra: endoscopy is needed before treatment in all patients with gastroesophageal reflux disease.

Most current endoscopic guidelines do not recommend the use of routine esophagoscopy in the evaluation of patients with typical symptoms of gastroesophageal reflux disease (GERD), unless alarm features are present. In patients with known reflux esophagitis, esophagoscopy is considered to have no role either in the further management or follow-up. Screening of reflux patients for Barrett's esophagus is not considered to be cost-effective. On the basis of a critical review of the available literature, and of some recent papers in particular, we disagree with these suggestions. We would argue, on the contrary, that a negative esophagoscopy can provide the GERD patient with reassurance, and that esophagoscopy allows targeted therapy to be offered if it is positive for esophagitis. When Barrett's esophagus is diagnosed, it usually leads to a surveillance program being initiated. The potential benefits of endoscopy for the patient's quality of life are probably underestimated when financial issues alone are taken into account. Even if it is true that a large percentage of GERD patients do not have endoscopic abnormalities (those with nonerosive reflux disease), surrogate tests such as the proton-pump inhibitor test or symptom questionnaires do not provide a more accurate diagnosis. We would therefore suggest that, at least in the specialist setting, all patients with suspected GERD should undergo accurate symptom analysis as well as endoscopic evaluation before treatment is started.