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Publication
Journal: Food and Chemical Toxicology
March/19/2008
Abstract
Ginger (Zingiber officinale Roscoe, Zingiberacae) is a medicinal plant that has been widely used in Chinese, Ayurvedic and Tibb-Unani herbal medicines all over the world, since antiquity, for a wide array of unrelated ailments that include arthritis, rheumatism, sprains, muscular aches, pains, sore throats, cramps, constipation, indigestion, vomiting, hypertension, dementia, fever, infectious diseases and helminthiasis. Currently, there is a renewed interest in ginger, and several scientific investigations aimed at isolation and identification of active constituents of ginger, scientific verification of its pharmacological actions and of its constituents, and verification of the basis of the use of ginger in some of several diseases and conditions. This article aims at reviewing the most salient recent reports on these investigations. The main pharmacological actions of ginger and compounds isolated therefrom include immuno-modulatory, anti-tumorigenic, anti-inflammatory, anti-apoptotic, anti-hyperglycemic, anti-lipidemic and anti-emetic actions. Ginger is a strong anti-oxidant substance and may either mitigate or prevent generation of free radicals. It is considered a safe herbal medicine with only few and insignificant adverse/side effects. More studies are required in animals and humans on the kinetics of ginger and its constituents and on the effects of their consumption over a long period of time.
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Publication
Journal: New England Journal of Medicine
March/11/1998
Abstract
BACKGROUND
Misoprostol is effective for ulcers associated with the use of nonsteroidal antiinflammatory drugs (NSAIDs) but is often poorly tolerated because of diarrhea and abdominal pain. We compared the efficacy of omeprazole and misoprostol in healing and preventing ulcers associated with NSAIDs.
METHODS
In a double-blind study, we randomly assigned 935 patients who required continuous NSAID therapy and who had ulcers or more than 10 erosions in the stomach or duodenum (or both) to receive 20 mg or 40 mg of omeprazole orally in the morning or 200 microg of misoprostol orally four times daily. Patients were treated for four weeks or, in the absence of healing, eight weeks. Treatment success was defined as the absence of ulcers and the presence of fewer than five erosions at each site and not more than mild dyspepsia. We then randomly reassigned 732 patients in whom treatment was successful to maintenance therapy with 20 mg of omeprazole daily, 200 microg of misoprostol twice daily, or placebo for six months.
RESULTS
At eight weeks, treatment was successful in 76 percent of the patients given 20 mg of omeprazole (233 of 308), 75 percent of those given 40 mg of omeprazole (237 of 315), and 71 percent of those given misoprostol (212 of 298). The rates of gastric-ulcer healing were significantly higher with 20 mg of omeprazole (but not 40 mg of omeprazole) than with misoprostol. Healing rates among patients with duodenal ulcers were higher with either dose of omeprazole than with misoprostol, whereas healing rates among patients with erosions alone were higher with misoprostol. More patients remained in remission during maintenance treatment with omeprazole (61 percent) than with misoprostol (48 percent, P=0.001) and with either drug than with placebo (27 percent, P<0.001). There were more adverse events during the healing phase in the misoprostol group than in the groups given 20 mg and 40 mg of omeprazole (59 percent, 48 percent, and 46 percent, respectively).
CONCLUSIONS
The overall rates of successful treatment of ulcers, erosions, and symptoms associated with NSAIDs were similar for the two doses of omeprazole and misoprostol. Maintenance therapy with omeprazole was associated with a lower rate of relapse than misoprostol. Omeprazole was better tolerated than misoprostol.
Publication
Journal: BMJ (Clinical research ed.)
March/18/1992
Abstract
OBJECTIVE
To determine the prevalence of symptoms compatible with a clinical diagnosis of irritable bowel syndrome in the general population.
METHODS
Validated postal questionnaire sent to 2280 subjects randomly selected in 10 year age bands from the lists of eight general practitioners. The Manning criteria were used to define irritable bowel syndrome.
METHODS
Urban population in Southampton and mixed urban-rural population in Andover, Hampshire.
RESULTS
A response of 71% yielded 1620 questionnaires for analysis, of which 412 (25%) reported more than six episodes of abdominal pain in the preceding year, with 350 (22%) reporting symptoms consistent with the diagnosis of irritable bowel syndrome. The male: female ratio was 1:1.38. More subjects with irritable bowel syndrome had constipation and diarrhoea and 35% with the syndrome reported rectal bleeding compared with an overall prevalence of 20%. Other symptoms and conditions including heartburn, dyspepsia, flushing, palpitations, migraine, and urinary symptoms were significantly more common in the group with irritable bowel syndrome. Abdominal pain in childhood was more common in the subjects with irritable bowel syndrome (12%) than without (3%). One third of the group with irritable bowel syndrome had sought medical advice during the study period (male:female ratio 1:1.21); consultation behaviour was influenced by age and the presence of associated symptoms, varied considerably among patients registered with different general practitioners, and was poorly correlated with symptom severity.
CONCLUSIONS
Symptoms consistent with a diagnosis of irritable bowel syndrome are present in almost one quarter of the general population and tend to be associated with a number of other complaints and conditions, some of which may reflect smooth muscle dysfunction.
Publication
Journal: Gastroenterology
June/5/1996
Abstract
OBJECTIVE
Although gastric dysmotility and dyspeptic symptoms are often associated, their relationship remains unclear. The aim of this study was to evaluate the relationship between gastric emptying abnormalities and clinical features in functional dyspepsia.
METHODS
In 343 patients with functional dyspepsia, the gastric emptying of solids was measured by a radioisotopic technique and four dyspeptic symptoms (epigastric pain and burning, postprandial fullness, nausea, and vomiting) were measured as absent, mild, relevant, and severe, according to their influence on patients' usual activities.
RESULTS
Delayed gastric emptying was detected in 33.5% of dyspeptics. Delayed gastric emptying was particularly frequent in patients characterized by female sex, low body weight, presence of relevant and severe postprandial fullness, nausea, vomiting, and absence of relevant and severe epigastric pain. Logistic regression showed that delayed gastric emptying was invariably associated with female sex and postprandial fullness (odds ratio, 2.34; 95% confidence interval, 1.45-3.75) and vomiting (odds ratio, 4.04; 95% confidence interval, 1.30-12.54) when coded as severe and only postprandial fullness (odds ratio, 3.78; 95% confidence interval, 1.78-8.01) when coded as relevant and severe.
CONCLUSIONS
Female sex, relevant and severe postprandial fullness, and severe vomiting are independently associated with delayed gastric emptying of solids in patients with functional dyspepsia seen in a referral center.
Publication
Journal: Gastroenterology
October/1/1995
Abstract
OBJECTIVE
It has been suggested that irritable bowel syndrome (IBS) and functional dyspepsia represent the same disease entity, the irritable gut. The aim of this study was to test the stability, consistency, and relevance of the current classification in the entire, unselected population of persons with gastrointestinal and/or abdominal symptoms, including those who had not consulted physicians.
METHODS
Sequential postal questionnaires were sent to 1290 representative persons (age range, 20-79 years) sampled from the population. Questions were asked about the prevalence of 24 gastrointestinal and/or abdominal symptoms and the site and type of abdominal pain, if any.
RESULTS
The prevalence of dyspepsia was 14% (32% if predominant reflux symptoms and concomitant IBS symptoms were included), and the prevalence of IBS was 12.5%. The 3-month incidence rates of reflux, dyspepsia, and IBS among previously symptomless persons were 0.5, 8, and 2 per 1000, respectively. Of persons with IBS, 87% also fulfilled the dyspepsia criteria, and the overlap between dyspepsia subgroups was more than 50%. The use of stricter criteria did not eliminate this overlap. Over a 1-year period, approximately 50% changed their symptom profile. Principal component analysis did not show any natural clustering of the symptoms.
CONCLUSIONS
The separation of functional gastrointestinal symptoms into dyspepsia, its subgroups, and IBS may be inappropriate.
Publication
Journal: Gut
September/8/1997
Abstract
There is considerable confusion over the management of Helicobacter pylori infection, particularly among primary care physicians, and numerous European countries lack national guidelines in this rapidly growing area of medicine. The European Helicobacter Pylori Study Group therefore organised a meeting in Maastricht of H pylori experts, primary care physicians and representatives of National Societies of Gastroenterology from Europe to establish consensus guidelines on the management of H pylori at the primary care and specialist levels, and to consider general health care issues associated with the infection. As in previous guidelines, eradication therapy was recommended in all H pylori positive patients with peptic ulcer disease. Additionally, at the primary care level in dyspeptic patients < 45 years old and with no alarm symptoms, diagnosis is recommended by non-invasive means (13C urea breath test, serology) and if H pylori positive the patient should be treated. Moreover, at the specialist level the indications for eradication of H pylori were also broadened to include H pylori positive patients with functional dyspepsia in whom no other possible causes of symptoms are identified by the specialist (after a full investigation including endoscopy, ultrasound and other necessary investigations), patients with low grade gastric mucosa associated lymphoid tissue (MALT) lymphoma (managed in specialised centres) and those with gastritis with severe macro- or microscopic abnormalities. There was consensus that treatment regimens should be simple, well tolerated and achieve an eradication rate of over 80% on an intention to treat basis. It was strongly recommended, therefore, that eradication treatment should be with proton pump inhibitor based triple therapy for seven days, using a proton pump inhibitor and two of the following: clarithromycin, a nitroimidazole (metronidazole or tinidazole) and amoxycillin.
Publication
Journal: Arthritis and rheumatism
September/14/2005
Abstract
OBJECTIVE
A 2-year randomized controlled trial was performed to test the hypothesis that long-term, continuous treatment with nonsteroidal antiinflammatory drugs (NSAIDs), in comparison with NSAID treatment on demand only, influences radiographic progression in patients with ankylosing spondylitis (AS).
METHODS
Patients with AS (n = 215), who had previously participated in a 6-week, randomized, double-blind clinical trial that compared celecoxib, ketoprofen, and placebo, were randomly allocated to receive either continuous treatment with NSAIDs or on-demand treatment with NSAIDs for a period of 2 years. All patients began treatment with celecoxib, at a starting dosage of 100 mg twice daily; patients could increase this dosage to 200 mg twice daily or could switch to another NSAID while maintaining the same treatment strategy. Structural changes were assessed by radiographs of the lumbar and cervical spine and scored according to the modified Stoke Ankylosing Spondylitis Spine Score by one observer who was blinded to the treatment strategy and temporal order of the radiographs. Statistical analyses included a between-group comparison of 1) radiographic progression scores (by Mann-Whitney U test), 2) time-averaged values of variables reflecting signs and symptoms of AS (by linear regression analysis), and 3) the frequency of reported site-specific adverse events (by chi-square test or Fisher's exact test, as appropriate).
RESULTS
Complete sets of radiographs were available for 76 of the 111 patients in the continuous-treatment group and for 74 of the 104 patients in the on-demand group. The mean +/- SD scores for radiographic progression were 0.4 +/- 1.7 in the continuous-treatment group and 1.5 +/- 2.5 in the on-demand treatment group (P = 0.002). Parameters reflecting signs and symptoms were not statistically significantly different between groups. The between-group difference in radiographic progression did not disappear after adjusting for baseline values of radiographic damage or disease activity variables and for time-averaged values of disease activity variables, nor after input of missing data. Relevant adverse events tended to occur more frequently in the continuous-treatment group than in the on-demand group (for hypertension, 9% versus 3%; for abdominal pain, 11% versus 6%; for dyspepsia, 41% versus 38%), but the differences were not statistically significant.
CONCLUSIONS
A strategy of continuous use of NSAIDs reduces radiographic progression in symptomatic patients with AS, without increasing toxicity substantially.
Publication
Journal: Gastroenterology
July/22/1997
Abstract
OBJECTIVE
We have identified a subgroup of Helicobacter pylori-infected subjects with low or absent gastric acid output. The aim of this study was to document the morphological and functional abnormalities in these subjects and to assess the effect of eradicating the infection.
METHODS
The 16 hypochlorhydric subjects (6 men) had a mean age of 55 years (range, 36-79 years). They underwent a 14C-urea breath test, H. pylori serology, fasting gastrin, gastric autoantibodies, gastroscopy with antral and body biopsies, and measurement of peak acid output to pentagastrin (PAO(PG)). Their histology was compared with that of age- and sex-matched duodenal ulcer and nonulcer dyspepsia patients (16 each). H. pylori infection was eradicated in the hypochlorhydric subjects, and the investigations were repeated 6 months later.
RESULTS
Compared with controls, the hypochlorhydric subjects had less dense H. pylori colonization, body-predominant colonization and gastritis, and increased prevalence of body atrophy and intestinal metaplasia. Median PAO(PG) before eradication in the hypochlorhydric subjects was 1.1 mmol/h and increased to 12.6 mmol/h after eradication (P < 0.001), with no significant change in body atrophy or intestinal metaplasia.
CONCLUSIONS
In some subjects, chronic H. pylori infection produces a body-predominant gastritis and profound suppression of gastric acid secretion that is partially reversible with eradication therapy.
Publication
Journal: Annals of Internal Medicine
October/29/1989
Abstract
Although functional gastrointestinal symptoms are seen frequently by internists and are the commonest reason for patients to be referred to gastroenterologists, no validated self-report questionnaire is available for their diagnosis. To differentiate among non-ulcer dyspepsia, the irritable bowel syndrome, organic gastrointestinal disease, and health, we developed a self-report questionnaire. Our bowel disease questionnaire, which evaluated 46 symptom-related items was completed prospectively by 361 subjects before their clinical evaluation as outpatients. Of these subjects, 115 were categorized ultimately as having functional bowel disease (non-ulcer dyspepsia or the irritable bowel syndrome), 101 were categorized ultimately as having organic gastrointestinal disease, and 145 were healthy persons having routine periodic examinations for whom no additional diagnoses were made. All diagnoses were based on independent clinical evaluations, not on the patients' responses to the questionnaire. The bowel disease questionnaire was acceptable and easily completed; it elicited symptoms in a highly reliable manner and was shown to be a valid measure of functional bowel complaints. Our questionnaire discriminated non-ulcer dyspepsia from irritable bowel syndrome with a sensitivity of 75% and a specificity of 72%, and it discriminated functional bowel disease from organic disease and health with sensitivities of 85% and 83%, and specificities of 60% and 76%, respectively. We believe that this questionnaire is an additional and useful diagnostic tool for identifying patients with functional gastrointestinal symptoms.
Publication
Journal: Annals of Internal Medicine
October/27/2008
Abstract
BACKGROUND
Oral sildenafil and intravenous epoprostenol have independently been shown to be effective in patients with pulmonary arterial hypertension.
OBJECTIVE
To investigate the effect of adding oral sildenafil to long-term intravenous epoprostenol in patients with pulmonary arterial hypertension.
METHODS
A 16-week, double-blind, placebo-controlled, parallel-group study.
METHODS
Multinational study at 41 centers in 11 countries from 3 July 2003 to 27 January 2006.
METHODS
267 patients with pulmonary arterial hypertension (idiopathic, associated anorexigen use or connective tissue disease, or corrected congenital heart disease) who were receiving long-term intravenous epoprostenol therapy.
METHODS
Patients were randomly assigned to receive placebo or sildenafil, 20 mg three times daily, titrated to 40 mg and 80 mg three times daily, as tolerated, at 4-week intervals. Of 265 patients who received treatment, 256 (97%) patients (123 in the placebo group and 133 in the sildenafil group) completed the study.
METHODS
Change from baseline in exercise capacity measured by 6-minute walk distance (primary end point) and hemodynamic measurements, time to clinical worsening, and Borg dyspnea score (secondary end points).
RESULTS
A placebo-adjusted increase of 28.8 meters (95% CI, 13.9 to 43.8 meters) in the 6-minute walk distance occurred in patients in the sildenafil group; these improvements were most prominent among patients with baseline distances of 325 meters or more. Relative to epoprostenol monotherapy, addition of sildenafil resulted in a greater change in mean pulmonary arterial pressure by -3.8 mm Hg (CI, -5.6 to -2.1 mm Hg); cardiac output by 0.9 L/min (CI, 0.5 to 1.2 L/min); and longer time to clinical worsening, with a smaller proportion of patients experiencing a worsening event in the sildenafil group (0.062) than in the placebo group (0.195) by week 16 (P = 0.002). Health-related quality of life also improved in patients who received combined therapy compared with those who received epoprostenol monotherapy. There was no effect on the Borg dyspnea score. Of the side effects generally associated with sildenafil treatment, the most commonly reported in the placebo and sildenafil groups, respectively, were headache (34% and 57%; difference, 23 percentage points [CI, 12 to 35 percentage points]), dyspepsia (2% and 16%; difference, 13 percentage points [CI, 7 to 20 percentage points]), pain in extremity (18% and 25%; difference, 8 percentage points [CI, -2 to 18 percentage points]), and nausea (18% and 25%; difference, 8 percentage points [CI, -2 to 18 percentage points]).
CONCLUSIONS
The study excluded patients with pulmonary arterial hypertension associated with other causes. There was an imbalance in missing data between groups, with 8 placebo recipients having no postbaseline walk assessment compared with 1 sildenafil recipient. These patients were excluded from the analysis.
CONCLUSIONS
In some patients with pulmonary arterial hypertension, the addition of sildenafil to long-term intravenous epoprostenol therapy improves exercise capacity, hemodynamic measurements, time to clinical worsening, and quality of life, but not Borg dyspnea score. Increased rates of headache and dyspepsia occurred with the addition of sildenafil.
Publication
Journal: Gut
October/27/2015
Abstract
OBJECTIVE
To present results of the Kyoto Global Consensus Meeting, which was convened to develop global consensus on (1) classification of chronic gastritis and duodenitis, (2) clinical distinction of dyspepsia caused by Helicobacter pylori from functional dyspepsia, (3) appropriate diagnostic assessment of gastritis and (4) when, whom and how to treat H. pylori gastritis.
METHODS
Twenty-three clinical questions addressing the above-mentioned four domains were drafted for which expert panels were asked to formulate relevant statements. A Delphi method using an anonymous electronic system was adopted to develop the consensus, the level of which was predefined as ≥80%. Final modifications of clinical questions and consensus were achieved at the face-to-face meeting in Kyoto.
RESULTS
All 24 statements for 22 clinical questions after extensive modifications and omission of one clinical question were achieved with a consensus level of >80%. To better organise classification of gastritis and duodenitis based on aetiology, a new classification of gastritis and duodenitis is recommended for the 11th international classification. A new category of H. pylori-associated dyspepsia together with a diagnostic algorithm was proposed. The adoption of grading systems for gastric cancer risk stratification, and modern image-enhancing endoscopy for the diagnosis of gastritis, were recommended. Treatment to eradicate H. pylori infection before preneoplastic changes develop, if feasible, was recommended to minimise the risk of more serious complications of the infection.
CONCLUSIONS
A global consensus for gastritis was developed for the first time, which will be the basis for an international classification system and for further research on the subject.
Publication
Journal: The Lancet Oncology
March/31/2015
Abstract
BACKGROUND
The poly(ADP-ribose) polymerase inhibitor olaparib has shown antitumour activity in patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer with or without BRCA1 or BRCA2 mutations. The aim of this study was to assess the efficacy and tolerability of olaparib in combination with chemotherapy, followed by olaparib maintenance monotherapy, versus chemotherapy alone in patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer.
METHODS
In this randomised, open-label, phase 2 study, adult patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer who had received up to three previous courses of platinum-based chemotherapy and who were progression free for at least 6 months before randomisation received either olaparib (200 mg capsules twice daily, administered orally on days 1-10 of each 21-day cycle) plus paclitaxel (175 mg/m(2), administered intravenously on day 1) and carboplatin (area under the curve [AUC] 4 mg/mL per min, according to the Calvert formula, administered intravenously on day 1), then olaparib monotherapy (400 mg capsules twice daily, given continuously) until progression (the olaparib plus chemotherapy group), or paclitaxel (175 mg/m(2) on day 1) and carboplatin (AUC 6 mg/mL per min on day 1) then no further treatment (the chemotherapy alone group). Randomisation was done by an interactive voice response system, stratified by number of previous platinum-containing regimens received and time to disease progression after the previous platinum regimen. The primary endpoint was progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1, analysed by intention to treat. Prespecified exploratory analyses included efficacy by BRCA mutation status, assessed retrospectively. This study is registered with ClinicalTrials.gov, number NCT01081951, and has been completed.
RESULTS
Between Feb 12 and July 30, 2010, 173 patients at 43 investigational sites in 12 countries were enrolled into the study, of whom 162 were eligible and were randomly assigned to the two treatment groups (81 to the olaparib plus chemotherapy group and 81 to the chemotherapy alone group). Of these randomised patients, 156 were treated in the combination phase (81 in the olaparib plus chemotherapy group and 75 in the chemotherapy alone group) and 121 continued to the maintenance or no further treatment phase (66 in the olaparib plus chemotherapy group and 55 in the chemotherapy alone group). BRCA mutation status was known for 107 patients (either at baseline or determined retrospectively): 41 (38%) of 107 had a BRCA mutation (20 in the olaparib plus chemotherapy group and 21 in the chemotherapy alone group). Progression-free survival was significantly longer in the olaparib plus chemotherapy group (median 12.2 months [95% CI 9.7-15.0]) than in the chemotherapy alone group (median 9.6 months [95% CI 9.1-9.7) (HR 0.51 [95% CI 0.34-0.77]; p=0.0012), especially in patients with BRCA mutations (HR 0.21 [0.08-0.55]; p=0.0015). In the combination phase, adverse events that were reported at least 10% more frequently with olaparib plus chemotherapy than with chemotherapy alone were alopecia (60 [74%] of 81 vs 44 [59%] of 75), nausea (56 [69%] vs 43 [57%]), neutropenia (40 [49%] vs 29 [39%]), diarrhoea (34 [42%] vs 20 [27%]), headache (27 [33%] vs seven [9%]), peripheral neuropathy (25 [31%] vs 14 [19%]), and dyspepsia (21 [26%] vs 9 [12%]); most were of mild-to-moderate intensity. The most common grade 3 or higher adverse events during the combination phase were neutropenia (in 35 [43%] of 81 patients in the olaparib plus chemotherapy group vs 26 [35%] of 75 in the chemotherapy alone group) and anaemia (seven [9%] vs five [7%]). Serious adverse events were reported in 12 (15%) of 81 patients in the olaparib plus chemotherapy group and 16 of 75 (21%) patients in the chemotherapy alone group.
CONCLUSIONS
Olaparib plus paclitaxel and carboplatin followed by maintenance monotherapy significantly improved progression-free survival versus paclitaxel plus carboplatin alone, with the greatest clinical benefit in BRCA-mutated patients, and had an acceptable and manageable tolerability profile.
BACKGROUND
AstraZeneca.
Publication
Journal: Quality of Life Research
March/18/1998
Abstract
The objective of this study was to evaluate the reliability and validity of the gastrointestinal Symptom Rating Scale (GSRS) in US patients with gastroesophageal reflux disease (GERD). Five hundred and sixteen adults with predominant heartburn symptoms of GERD were recruited from gastroenterologist and family physician practices and treated with 6 weeks of 150 mg ranitidine twice daily to identify poorly responsive symptomatic GERD. The GSRS, the Medical Outcomes Study Short Form-36 (SF-36) Health Survey and the Psychological General Well-being (PGWB) scale were administered at baseline and after 6 weeks of treatment. Reported ratings of GERD-related symptoms from physician and patient diaries were measured. The GSRS contains five scales: reflux syndrome, abdominal pain, constipation syndrome, diarrhoea syndrome and indigestion syndrome. The internal consistency reliabilities for the GSRS scales ranged from 0.61 to 0.83 and the intraclass correlation coefficients ranged from 0.42 to 0.60. The GSRS scale scores were correlated with the SF-36 and PGWB scales and with the number and severity of heartburn symptoms. Patients with two or three clinician-rated GERD-related symptoms reported worse GSRS scale scores compared with patients with fewer symptoms (p < 0.0001). Statistically significant differences in the mean GSRS scale scores were observed between treatment responders and non-responders (p < 0.0001) and patients showing a response to treatment had larger mean changes in their GSRS scales than patients not showing a response to treatment (p < 0.0001). The standardized response means ranged from 0.42 to 1.43 for the GSRS scale scores. It was concluded that the GSRS is a brief, fairly comprehensive assessment of common gastrointestinal symptoms. The GSRS has good reliability and construct validity and the GSRS scales discriminate by GERD symptom severity and are responsive to treatment. The GSRS is a useful patient-rated symptom scale for evaluating the outcomes of treatment for GERD.
Publication
Journal: Digestive Diseases and Sciences
December/6/1998
Abstract
Patients with gastroparesis frequently present challenging clinical, diagnostic, and therapeutic problems. Data from 146 gastroparesis patients seen over six years were analyzed. Patients were evaluated at the time of initial diagnosis and at the most recent follow-up in terms of gastric emptying and gastrointestinal symptomatology. The psychological status and physical and sexual abuse history in female idiopathic gastroparesis patients were ascertained and an association between those factors and gastrointestinal symptomatology was sought. Eighty-two percent of patients were females (mean age: 45 years old). The mean age for onset of gastroparesis was 33.7 years. The etiologies in 146 patients are: 36% idiopathic, 29% diabetic, 13% postgastric surgery, 7.5% Parkinson's disease, 4.8% collagen vascular disorders, 4.1% intestinal pseudoobstruction, and 6% miscellaneous causes. Subgroups were identified within the idiopathic group: 12 patients (23%) had a presentation consistent with a viral etiology, 48% had very prominent abdominal pain. Other subgroups were gastroesophageal reflux disease and nonulcer dyspepsia (19%), depression (23%), and onset of symptoms immediately after cholecystectomy (8%). Sixty-two percent of women with idiopathic gastroparesis reported a history of physical or sexual abuse, and physical abuse was significantly associated with abdominal pain, somatization, depression, and lifetime surgeries. At the end of the follow-up period, 74% required continuous prokinetic therapy, 22% were able to stop prokinetics, 5% had undergone gastrectomy, 6.2% went onto gastric electrical stimulation (pacing), and 7% had died. At some point 21% had required nutrition support with a feeding jejunostomy tube or periods of parenteral nutrition. A good response to pharmacological agents can be expected in the viral and dyspeptic subgroups of idiopathics, Parkinson's disease, and the majority of diabetics, whereas a poorer outcome to prokinetics can be expected in postgastrectomy patients, those with connective tissue disease, a subgroup of diabetics, and the subset of idiopathic gastroparesis dominated by abdominal pain and history of physical and sexual abuse. Appreciation of the different etiologies and psychological status of the patients may help predict response to prokinetic therapy.
Publication
Journal: Journal of gastrointestinal and liver diseases : JGLD
April/26/2011
Abstract
OBJECTIVE
Prevalence of H. pylori antibiotic resistance is increasing worldwide, and it is the main factor affecting efficacy of current therapeutic regimens. Our aim was to review recent data on H. pylori resistance towards antibiotics in different countries.
METHODS
A systematic review of studies concerning primary H. pylori antibiotic resistance published through January 2006 to December 2009 was performed. Data were analyzed according to geographic area, age, sex, and gastroduodenal pathology.
RESULTS
The overall H. pylori antibiotic resistance rates were 17.2% (95% CI: 16.5-17.9%) for clarithromycin, 26.7% (95% CI: 25.2-28.1%) for metronidazole, 11.2% (95% CI: 9.6-12.7%) for amoxycillin, 16.2% (95% CI: 14.4-18%) for levofloxacin, 5.9% (95% CI: 4.7-7.1%) for tetracycline, 1.4% (95% CI: 0.81-9%) for rifabutin and 9.6% (95% CI: 8.5-10.7%) for multiple antibiotics. Prevalence rate of clarithromycin, metronidazole, and levofloxacin resistance significantly increased from Europe to Asia, America and Africa. Tetracycline resistance is low (<3%) in all countries, but Africa (43.9%). Prevalence of clarithromycin resistance was higher in non-ulcer dyspepsia patients, whilst metronidazole resistance was higher in peptic ulcer patients. Both resistances were significantly higher in female than in male patients. Data regarding amoxicillin resistance are highly conflicting.
CONCLUSIONS
The worldwide H. pylori antibiotic resistance towards different antibiotics has increased. Such a phenomenon may affect therapeutic management in different countries.
Publication
Journal: New England Journal of Medicine
March/11/1998
Abstract
BACKGROUND
Suppressing acid secretion is thought o reduce the risk of ulcers associated with regular use of nonsteroidal antiinflammatory drugs (NSAIDs), but the best means of accomplishing this is uncertain.
METHODS
We studied 541 patients who required continuous treatment with NSAIDs and who had ulcers or more than 10 erosions in either the stomach or duodenum. Patients were randomly assigned to double-blind treatment with omeprazole, 20 mg or 40 mg orally per day, or ranitidine, 150 mg orally twice a day, for four or eight weeks, depending on when treatment was successful (defined as the resolution of ulcer and the presence of fewer than five erosions in the stomach, and fewer than five erosions in the duodenum, and not more than mild dyspepsia). We randomly assigned 432 patients in whom treatment was successful to maintenance treatment with either 20 mg of omeprazole per day or 150 mg of ranitidine twice a day for six months.
RESULTS
At eight weeks, treatment was successful in 80 percent (140 of 174) of the patients in the group given 20 mg of omeprazole per day, 79 percent (148 of 187) of those given 40 mg of omeprazole per day, and 63 percent (110 of 174) of those given ranitidine (P<0.001 for the comparison with 20 mg of omeprazole and P=0.001 for the comparison with 40 mg of omeprazole). The rates of healing of all types of lesions were higher with omeprazole than with ranitidine. During maintenance therapy, the estimated proportion of patients in remission at the end of six months was 72 percent in the omeprazole group and 59 percent in the ranitidine group. The rates of adverse events were similar between groups during both phases. Both medications were well tolerated.
CONCLUSIONS
In patients with regular use of NSAIDs, omeprazole healed and prevented ulcers more effectively than did ranitidine.
Publication
Journal: Annals of Surgery
June/26/2006
Abstract
OBJECTIVE
Gastric gastrointestinal stromal tumors (GISTs) are rare neoplasms that require excision for cure. Although the feasibility of minimally invasive resection of gastric GIST has been established, the long-term safety and efficacy of these techniques are unclear. We hypothesized that complete resection of gastric GISTs using a combination of laparoscopic or laparoendoscopic techniques results in low perioperative morbidity and an effective long-term control of the disease.
METHODS
Between August 1996 and June 2005, 50 consecutive patients undergoing laparoscopic or laparoendoscopic resection of gastric GISTs were identified in a prospectively collected database. Outcome measures included patient demographics and outcomes, operative findings, morbidity, and histopathologic characteristics of the tumor. Patient and tumor characteristics were analyzed to identify risk factors for tumor recurrence.
RESULTS
Fifty patients, mean age 60 years (range, 34-84 years), underwent 47 local and 3 segmental laparoscopic gastric resections. GI bleeding and dyspepsia were the most common symptoms. Mean tumor size was 4.4 cm (range, 1.0-8.5 cm) with the majority of the lesions located in the proximal stomach. Mean operative time was 135 minutes (range, 49-295 minutes), the mean blood loss was 85 mL (range, 10-450 mL), and the mean length of hospitalization was 3.8 days (range 1-10 days). There were no major perioperative complications or mortalities. All lesions had negative resection margins (range, 2-45 mm). Nine patients had 10 or more mitotic figures per 50 high power fields, while 11 had ulceration and/or necrosis of the lesion. At a mean follow-up of 36 months, 46 (92%) patients were disease free, 1 patient was alive with disease, 1 patient with metastases died of a cardiac event, and 2 (4%) patients died of metastatic disease. No local or port site recurrences have been identified. Patient age, tumor size, mitotic index, tumor ulceration, and necrosis were statistically associated with tumor recurrence. The presence of 10 or more mitotic figures per 50 high power fields was an independent predictor of disease progression (P = 0.006).
CONCLUSIONS
A laparoscopic approach to surgical resection of gastric GIST is associated with low morbidity and short hospitalization. As found in historical series of open operative resection, the tumor mitotic index predicts local recurrence. The long-term disease-free survival of 92% in our study establishes laparoscopic resection as safe and effective in treating gastric GISTs. Given these findings as well as the advantages afforded by minimally invasive surgery, a laparoscopic approach may be the preferred resection technique in most patients with small- and medium-sized gastric GISTs.
Publication
Journal: Gut
September/8/1996
Abstract
BACKGROUND
Helicobacter pylori may promote gastric carcinogenesis through increasing gastric epithelial cell proliferation. How H pylori does so is unknown. Programmed, non-necrotic, cell death (apoptosis) occurs throughout the gut and is linked to proliferation. It was hypothesised that H pylori may induce hyper-proliferation through increasing apoptosis.
OBJECTIVE
To measure the effect of H pylori infection on gastric epithelial apoptosis in situ.
METHODS
Patients with duodenal ulcers treated to eradicate H pylori and patients with H pylori negative non-ulcer dyspepsia.
METHODS
Retrospective quantification of apoptotic epithelial cells in situ from formalin fixed biopsy specimens, counted after staining by terminal uridine deoxynucleotidyl nick end-labelling.
RESULTS
In the uninfected stomach, apoptotic cells were rare and situated in the most superficial portion of gastric glands (mean 2.9% of epithelial cells). In H pylori infection, they were more numerous and were located throughout the depth of gastric glands, comprising 16.8% of epithelial cells, falling to 3.1% after H pylori eradication, p = 0.017. Apoptotic cell number did not correlate with the degree of histological gastritis.
CONCLUSIONS
These results suggest that H pylori induces epithelial apoptosis in vivo. Increased apoptosis may be the stimulus for a compensatory hyperproliferative and potentially preneoplastic response in chronic H pylori infection.
Publication
Journal: Microbiome
July/26/2017
Abstract
Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children.
MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks).
This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact.
This trial was registered on the ClinicalTrials.gov, with the registration number NCT02504554.
Publication
Journal: Mayo Clinic Proceedings
December/25/1990
Abstract
A need exists for a self-report questionnaire that reliably and accurately measures symptoms and that distinguishes patients with functional gastrointestinal disease from those with other conditions. We have developed such an instrument, the bowel disease questionnaire, and herein describe details of its discriminatory validity. Data from 399 subjects were analyzed. Patients with gastrointestinal symptoms were ultimately diagnosed as having functional gastrointestinal disease (82 with the irritable bowel syndrome and 33 with functional dyspepsia) or organic gastrointestinal disease (N = 101). There were 145 healthy control subjects and 38 patients with a psychiatric disease, somatoform disorder (which includes those with a diagnosis of hypochrondriasis, psychogenic pain, and somatization or conversion disorder). All subjects completed the questionnaire before undergoing an independent diagnostic assessment by experienced physicians. Functional gastrointestinal disease could be distinguished from organic disease, somatoform disorder, and health by using models derived from logistic discriminant analysis. With use of these models, the estimated probability of functional gastrointestinal disease was then calculated. Descriptive symptom scores were of less value than the scores derived from the data sets by logistic discriminant analysis. Age did not significantly affect the responses to the questionnaire items. We conclude that, in the population studied, the bowel disease questionnaire is a valid measure of symptoms of functional gastrointestinal disease, and this instrument may have clinical and research applications.
Publication
Journal: Gastroenterology
July/2/2002
Abstract
OBJECTIVE
Visceral hypersensitivity was detected in patients with functional gastrointestinal disorders and has been proposed as a biological marker of irritable bowel syndrome (IBS). The purpose of this study was to assess the sensitivity, specificity, and the predictive values of pain thresholds evaluated by rectal distention using an electronic barostat in patients with or without IBS and in control subjects.
METHODS
Patients were diagnosed according to Rome II criteria. Rectal sensory thresholds were determined in 164 patients (86 IBS patients, 26 painless constipation, 21 functional dyspepsia, and 31 miscellaneous conditions) and in 25 normal controls. All subjects underwent a series of rectal isobaric distentions using an electronic barostat. The bag was progressively distended from 0 to 48 mm Hg and, in response to distention, subjects reported on discomfort or pain.
RESULTS
Pain thresholds were lower in IBS patients (30.4 +/- 6.7 mm Hg) compared with controls (44.5 +/- 5), painless constipated (45.4 +/- 5.3), functional dyspepsia (39.4 +/- 7.8), and miscellaneous patients (43.2 +/- 5.5). At the level of 40 mm Hg, the sensitivity of the rectal barostat to identify IBS patients from normal subjects and non-IBS patients was 95.5% and its specificity was 71.8%. The positive predictive value was 85.4%. The negative predictive value was 90.2%.
CONCLUSIONS
Lowered rectal pain threshold is a hallmark of IBS patients. Rectal barostat testing is useful to confirm the diagnosis of IBS and to discriminate IBS from other causes of abdominal pain.
Publication
Journal: BMJ (Clinical research ed.)
May/16/1995
Abstract
OBJECTIVE
To determine the risks of hospitalisation for bleeding peptic ulcer with the current prophylactic aspirin regimens of 300 mg daily or less.
METHODS
A case-control study with hospital and community controls.
METHODS
Hospitals in Glasgow, Newcastle, Nottingham, Oxford, and Portsmouth.
METHODS
1121 patients with gastric or duodenal ulcer bleeding matched with hospital and community controls.
RESULTS
144 (12.8%) cases had been regular users of aspirin (taken at least five days a week for at least the previous month) compared with 101 (9.0%) hospital and 77 (7.8%) community controls. Odds ratios were raised for all doses of aspirin taken, whether compared with hospital or community controls (compared with combined controls: 75 mg, 2.3 (95% confidence interval 1.2 to 4.4); 150 mg, 3.2 (1.7 to 6.5); 300 mg, 3.9 (2.5 to 6.3)). Results were not explained by confounding influences of age, sex, prior ulcer history or dyspepsia, or concurrent non-aspirin non-steroidal anti-inflammatory drug use. Risks seemed particularly high in patients who took non-aspirin non-steroidal anti-inflammatory drugs concurrently.
CONCLUSIONS
No conventionally used prophylactic aspirin regimen seems free of the risk of peptic ulcer complications.
Publication
Journal: Gastroenterology
October/16/1991
Abstract
It was hypothesized that symptoms in functional dyspepsia are originated by an altered mechanism at the brain-gut axis (one or several) in the process of gastric accommodation to a meal. To test the key mechanisms potentially involved in symptomatic gastric accommodation, the sensorial responses (on a 0-10 perception score) and the gastric tone responses (by electronic barostat) to either gastric accommodation (n = 10) or to cold stress (n = 10) were measured in 20 patients with functional dyspepsia and 20 healthy controls. The mechanical accommodation of the stomach to gastric distention (compliance) was similar in patients (52 +/- 8 mL/mm Hg) and controls (57 +/- 6 mL/mm Hg). However, isobaric gastric distention elicited more upper abdominal discomfort in dyspeptics than in controls (perception scores, 4.7 +/- 0.9 vs. 1.1 +/- 0.5, respectively; mean +/- SE; P less than 0.005). Cold stress induced a similar gastric relaxatory response in dyspeptics and controls (delta vol, 145 mL +/- 40 mL vs. 141 mL +/- 42 mL, respectively); hand perception (scores, 8.3 +/- 0.4 vs. 7.9 +/- 0.4, respectively) and autonomic responses were also similar. It is concluded that an abnormal afferent sensorial pathway (altered gastric perception) may be a major mechanism of symptom production in functional dyspepsia.
Publication
Journal: Gastroenterology
September/19/2001
Abstract
OBJECTIVE
Hypersensitivity to gastric distention has been reported in functional dyspepsia, but its characteristics and relevance to symptoms remain unclear. The aim of this study was to define hypersensitivity to gastric distention and its association to specific symptoms in functional dyspepsia.
METHODS
We used a gastric barostat to study sensitivity to gastric distention in 80 healthy subjects and in 160 functional dyspepsia patients. Demographic characteristics, gastric emptying, Helicobacter pylori status, gastric accommodation, and a dyspepsia symptom score were obtained from all patients and the relationship with visceral sensitivity was assessed using univariate and multivariate analysis.
RESULTS
The increase of intra-balloon pressure over intra-abdominal pressure needed to induce discomfort or pain is the most appropriate expression of sensitivity to gastric distention because it yields a meaningful lower range of normal and it is independent from age and body mass index. Hypersensitivity to gastric distention was found in 34% of the patients, who did not differ from the other patients in demographic and other pathophysiological characteristics. Hypersensitivity to distention was associated with a higher prevalence of postprandial pain, belching, and weight loss.
CONCLUSIONS
Hypersensitivity to gastric distention is present in a subset of functional dyspepsia patients. It is associated with symptoms of postprandial epigastric pain, belching, and weight loss.
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