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Nicholas J Talley

Publications and source records attributed to Nicholas J Talley.

141 records · Page 8Linked to original sources
PubMed2002

Do changes in visceral sensory function determine the development of dyspepsia during treatment with aspirin?

BACKGROUND & AIMS: We hypothesized that the development of dyspeptic symptoms during treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) would be linked to alterations in gastric mechanosensory function and gastric emptying. METHODS: In the first study, gastric mechanosensory thresholds (barostat technique) and gastric emptying ((13)C-octanoic breath test) were measured and endoscopy was performed at entry and after 5 days of treatment with aspirin (500 mg 3 times daily) in 8 patients with functional dyspepsia (initially without symptoms) and 8 healthy controls. In a second, double-blind, placebo-controlled, cross-over study, 6 new patients with functional dyspepsia and 6 controls were started with either placebo or aspirin for 5 days. Sensory thresholds were tested after the fifth day of aspirin or placebo treatment. Abdominal symptoms were assessed daily. RESULTS: In the first study, 6 of 8 patients and 3 of 8 controls, and in the second trial 6 of 6 patients and 1 of 6 healthy subjects, developed dyspepsia on aspirin (P < 0.005 patients vs. healthy subjects). No symptoms occurred during placebo treatment. Lanza scores were not associated with symptoms. After aspirin, sensory thresholds increased in both studies in subjects without development of symptoms (by 25.9% +/- 7.9%, and 31.0% +/- 4.1%, respectively, all P < 0.05), whereas there was no significant increase in subjects who developed symptoms (-11.2% +/- 5.3% and -3.4% +/- 13.4%, all P > 0.4). Neither thresholds nor symptoms were linked with the severity of mucosal damage, baseline gastric emptying (t1/2), or changes of gastric emptying (all P > 0.4). CONCLUSIONS: Failure to increase sensory thresholds during treatment with aspirin is associated with the development of dyspepsia.

Adult↗
PubMed2002

A randomized comparison of quadruple and triple therapies for Helicobacter pylori eradication: The QUADRATE Study.

BACKGROUND & AIMS: Direct comparisons of bismuth and proton pump inhibitor (PPI)-based triple and quadruple therapies for Helicobacter pylori eradication are lacking. To address this, a randomized study was conducted. METHODS: Infected dyspeptic patients received pantoprazole 40 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, all twice daily, for 7 days (PAC7); or pantoprazole 40 mg twice daily, bismuth subcitrate 108 mg, and tetracycline 500 mg, both 4 times daily, and metronidazole 200 mg 3 times daily and 400 mg at night for 7 days (PBTM7); bismuth subcitrate 108 mg and tetracycline 500 mg, both 4 times daily, and metronidazole 200 mg 3 times daily and 400 mg at night for 14 days (BTM14). Outcome was assessed with (13)C-urea breath test. RESULTS: Eradication rates (intention to treat [n = 405]/per protocol [n = 320]) were similar for PAC7 (78%/82%) and PBTM7 (82%/88%); the latter significantly superior to BTM14 (69%/74%; P < 0.01). Pretreatment metronidazole resistance (MR) was 53% and clarithromycin resistance was 8%. Eradication rates for primary metronidazole sensitive/resistant isolates were 74%/87% with PAC7 and 80%/81% for PBTM7, compared with 76%/55% (P < 0.02) for BTM14. Noncompliance was greater with BTM14 (15%; P < 0.001) than PAC7 (3%) or PBTM7 (6%). Moderate-severe adverse events were more common with BTM14 (45%; P < 0.001), than PAC7 (23%) or PBTM7 (25%) with more discontinuations (9%, 2%, 3%, respectively). CONCLUSIONS: One-week PPI triple therapy is well tolerated and effective. The addition of PPI to bismuth triple therapy allows reduction of treatment duration with improved efficacy and tolerability, despite a high rate of MR. Quadruple therapy appears to overcome pretreatment MR in most cases. Two-week bismuth triple therapy is significantly inferior to quadruple therapy and less well tolerated than both 1-week therapies.

Adult↗
PubMed2002

Esomeprazole 40 mg and 20 mg is efficacious in the long-term management of patients with endoscopy-negative gastro-oesophageal reflux disease: a placebo-controlled trial of on-demand therapy for 6 months.

BACKGROUND: On-demand therapy may offer an effective approach to the long-term management of gastro-oesophageal reflux disease (GORD) without oesophagitis. AIM: To examine the efficacy of the novel proton pump inhibitor esomeprazole as on-demand therapy in endoscopy-negative GORD. PATIENTS AND METHODS: Endoscopy-negative GORD patients who achieved complete resolution of heartburn after short-term esomeprazole or omeprazole treatment (n = 721) were randomized to esomeprazole 20 mg (n = 282), 40 mg (n = 293) or placebo (n = 146) on demand (maximum one dose/day) for 6 months. The primary and secondary efficacy endpoints were time to study discontinuation due to (i) unwillingness to continue and (ii) inadequate control of heartburn, respectively. RESULTS: Both doses of esomeprazole were more effective than placebo. During the 6-month period, 42% of placebo recipients discontinued treatment due to unwillingness to continue, compared with 8% and 11% of esomeprazole 20 mg and 40 mg recipients, respectively. Overall, more patients treated with esomeprazole were free from gastrointestinal symptoms after 6 months of on-demand therapy. CONCLUSIONS: Esomeprazole 20 mg was superior to placebo for on-demand treatment of GORD; a higher dose did not confer additional clinical benefit. Over 90% of patients were willing to continue on-demand treatment with esomeprazole 20 mg over a 6-month period.

Administration, Oral↗
PubMed2002

GI symptoms in diabetes mellitus are associated with both poor glycemic control and diabetic complications.

OBJECTIVE: Diabetes mellitus is associated with an increased prevalence of GI symptoms, but the mechanisms underlying symptoms are poorly defined and controversial. We aimed to determine whether there is a relationship between GI symptoms and both diabetic complications and glycemic control. METHODS: We performed a cross-sectional questionnaire study of 1101 subjects with diabetes mellitus recruited from outpatient clinics (n = 209) and the community (n = 892). Data on eight GI symptom groups, complications of diabetes (retinopathy, neuropathy, nephropathy), and self-reported glycemic control were obtained from a validated questionnaire. Glycated hemoglobin was measured in 463 of the subjects, The association between diabetic complications, glycemic control, and GI symptoms was assessed using logistic regression analysis, adjusted for demographic and clinical factors. RESULTS: Of the 1101 subjects, 57% reported at least one complication. Diabetic complications were independently associated with both symptom complexity (number of symptom groups reported) (adjusted odds ratio = 1.92 per symptom group [95% CI = 1.51-2.45]) and seven of the eight GI symptom groups. For all symptom groups, the association was explained by self-reported symptoms of peripheral neuropathy. Poor glycemic control measured by both self-report and Hb A1c was an independent risk factor for upper GI symptoms, whereas other potential risk indicators, including duration and type of diabetes, were not significant. CONCLUSIONS: GI symptoms in diabetes mellitus may be linked to diabetic complications, particularly peripheral neuropathy, and to poor glycemic control.

Adult↗
PubMed2002

Epidemiology and health care seeking in the functional GI disorders: a population-based study.

OBJECTIVES: Functional GI disorders (FGIDs) are common in clinical practice, but little is known about the epidemiology of these disorders in the general population. We aimed to determine the prevalence, association with psychological morbidity, and health care seeking behavior of FGIDs in the population. METHODS: A random sample of subjects (n = 4500) aged > or = 18 yr and representative of the Australian population were mailed a validated questionnaire. For these subjects we measured all Rome I GI symptoms and physician visits over the past 12 months, as well as neuroticism, anxiety, depression, and somatic distress. RESULTS: The response rate for the study was 72%. The prevalence of any FGID was 34.6%, and 62.1% of these subjects had consulted a physician. There was considerable overlap of the FGIDs (19.2% had more than two disorders). Independent predictors for an FGID diagnosis were neuroticism, somatic distress, anxiety, bowel habit disturbance, abdominal pain frequency, and increasing age. However, psychological morbidity did not independently discriminate between consulters and nonconsulters with an FGID. CONCLUSIONS: More than one third of the general population have one or more FGIDs. There seems to be a modest link between psychological morbidity and FGIDs, although other unknown factors seem to be more important in explaining health care seeking for these disorders.

Adolescent↗
PubMed2002

Management of peptic ulcer disease not related to Helicobacter pylori or NSAIDs.

Helicobacter pylori (H. pylori) infection is widely accepted as the most important factor in the pathogenesis of duodenal ulcer. However, in parallel with more effective eradication of H. pylori, the prevalence of H. pylori is changing, and H. pylori-negative peptic ulcer disease appears to be increasing. When making a diagnosis of H. pylori-negative peptic ulcer disease, it is essential to avoid misclassification because of inaccurate diagnosis. In addition, secondary causes may need to be excluded with appropriate investigations. In the absence of H. pylori, nonsteroidal anti-inflammatory drug usage is the most common cause of peptic ulcer; surreptitious nonsteroidal anti-inflammatory drug usage is a cause of unexplained ulcer disease in up to 60% of patients. Hypersecretory syndromes such as Zollinger-Ellison syndrome, although rare, need to be excluded. Once all known etiological factors are excluded, there remains a group of patients with so-called "idiopathic ulcers." The interplay of etiological factors in the pathogenesis of idiopathic peptic ulcer disease is poorly defined but may include a genetic predisposition, altered acid secretion, rapid gastric emptying, defective mucosal defense mechanisms, psychological stress, and smoking. The management of idiopathic peptic ulcers is not defined; they appear to be more resistant to standard therapy, can be associated with more frequent complications, and those that relapse may require long-term maintenance therapy.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Predictors of turnover of lower gastrointestinal symptoms in diabetes mellitus.

BACKGROUND: Both the natural history of GI symptoms and factors influencing symptom turnover in diabetes mellitus are unknown. We aimed to determine the natural history of GI symptoms in diabetes mellitus over a 3-yr period. METHODS: Subjects with predominantly Type 2 diabetes on the mailing list of Diabetes Australia were recruited and completed a validated questionnaire (n = 892); of these, 64% completed the questionnaire again 3 yr later. Subjects were classified as never having GI symptoms (abdominal pain, constipation, diarrhea, fecal incontinence), fluctuating (only on one survey), or persistent symptoms. RESULTS: Symptoms more often fluctuated than persisted, but the prevalence at recruitment and 3 yr later was similar. Predictors of symptom turnover varied. In a multivariate model, abnormal sweating and diabetic foot problems predicted symptom turnover for abdominal pain (OR = 2.01, 95% CI = 1.07-3.76 and 2.54, 1.23-5.24, respectively), and paresthesiae ("pins and needles") and foot problems predicted fecal incontinence (OR = 2.24, 1.06-4.75 and 2.38, 1.04-5.45, respectively), but not constipation or diarrhea. Symptom turnover in constipation was associated with depression (OR = 2.73, CI = 1.89-3.94) and neuroticism (OR = 0.57, CI = 0.36-0.89), and depression was associated with abdominal pain (OR = 1.56, CI = 1.02-2.38), but psychological factors were not related to the other symptoms. The odds for symptoms persisting were not generally related to type or duration of diabetes, or self-rated glycemic control. CONCLUSION: The natural history of GI symptoms in diabetes has been described for the first time; symptoms may either persist or fluctuate, but the prevalence is constant because symptom onset is balanced by disappearance. Glycemic control does not seem to predict symptom change.

Chronic Disease↗
PubMed2002

Topographic association of gastric epithelial expression of Ki-67, Bax, and Bcl-2 with antralization in the gastric incisura, body, and fundus.

OBJECTIVES: Helicobacter pylori (H. pylon) infection seems to induce antralization (ie., gastric mucosal transformation from transitional or body type to antral type), which is strongly associated with gastric atrophy and intestinal metaplasia. The aim of this study was to determine the topographic associations of Ki-67 (a protein expressed in proliferative cells), Bax (a pro-apoptotic protein), and Bcl-2 (an antiapoptotic protein) expression with antralization. METHODS: In each of 104 patients, eight biopsy specimens were taken from the gastric antrum, incisura, body, and fundus for the determination of H. pylori infection, histological changes, and epithelial expression of Ki-67, Bax, and Bcl-2. A labeling index (LI), i.e., the rate of positive cells over total cells counted, was used for Ki-67 and Bax expression. Bcl-2 overexpression was considered to be present if the rate of Bcl-2 positive cells over total cells counted was > or = 5%. RESULTS: H. pylori infection was present at the gastric antrum, incisura, body, and fundus in 50, 48, 51, and 49 patients, respectively. Ki-67 LI was greater in the presence vs absence) of H. pylori infection at the antrum (51 vs 40), incisura (47 vs 36), body (43 vs 30), and fundus (41 vs 31) (all p < 0.001). At the incisura, Ki-67 LI was greater (47 vs 32, p < 0.001), Bax LI was lower (22 vs 30, p < 0.05), and prevalence of Bcl-2 overexpression was higher (44% vs 18%, p < 0.001) in the presence (vs absence) of antralization. Compared with normal mucosa, gastric atrophy/intestinal metaplasia were associated with an increased Ki-67 LI and decreased Bax LI at the antrum (49 vs 32 and 15 vs 23, respectively), incisura (47 vs 32 and 15 vs 26, respectively) (all p < 0.001). Bcl-2 overexpression was more frequent in gastric atrophy/intestinal metaplasia at the antrum (56% vs 11%, p < 0.001) and incisura (63% vs 19%, p < 0.001) compared with normal mucosa. CONCLUSIONS: Antralization at the incisura is topographically associated with increased cell proliferation, reduced Bax expression, and Bcl-2 overexpression, which implies that antralization may be an important histological marker for future cancer risk.

Adult↗
PubMed2002

Alternative and rescue treatment regimens for Helicobacter pylori eradication.

Eradication therapy has been incorporated into clinical practice. The regimens currently recommended for first-line treatment include a 2-week bismuth-based triple therapy (mainly in developing countries), a 1 - 2 week proton pump inhibitor (PPI)-based triple therapy and a 1-week ranitidine bismuth citrate (RBC)-based triple therapy. However, these regimens fail to eradicate Helicobacter pylori in up to 20% of patients due to poor compliance, inadequate treatment duration, smoking, old age and bacterial resistance to nitroimidazoles and/or macrolides in particular. Therefore, alternative regimens that avoid nitroimidazoles and/or macrolides or overcome bacterial resistance to these drugs, improve compliance, minimise side effects and/or reduce costs have been evaluated. One-week quadruple therapy, which adds a PPI or histamine receptor 2-blocker to bismuth-based triple therapy, usually achieves an eradication rate of 90% when used as an alternative first-line therapy but the efficacy decreases when used as a rescue therapy. Several new triple therapies that may be used as alternative and/or rescue therapies have been evaluated. Among these are furazolidone-based (furazolidone plus an antibiotic and a bismuth salt, a PPI or RBC), fluoroquinolone-based (levofloxacin or moxifloxacin plus an antibiotic and a PPI) and ecabet sodium-based (ecabet plus two antibiotics) triple therapies. Recently, rifabutin has been used in combination with a PPI and amoxycillin as a rescue therapy, with satisfactory eradication rates. In addition, a number of new antimicrobial agents are currently under investigation in in vitro studies but the clinical values of these agents needs to be confirmed.

Anti-Bacterial Agents↗
PubMed2002

New and emerging treatments for irritable bowel syndrome and functional dyspepsia.

The symptomatic management of irritable bowel syndrome (IBS) and functional dyspepsia, which often overlap, can be frustrating and difficult. Education and reassurance remain central for management although controlled trials are lacking. Psychological interventions may be useful in select patients but methodological inadequacies in clinical trials limit their interpretability. For symptom exacerbations, drug treatment is reasonable but no current treatment successfully targets the full symptom complex. Bulking agents are not of proven efficacy in IBS; they may improve constipation but worsen bloating and pain. Anticholinergics are of uncertain value in IBS. A meta-analysis of trials of smooth muscle relaxants for IBS has been reported to be positive but the quality of the trials included was poor. Antidepressants for IBS and functional dyspepsia appear to be efficacious based on the limited published evidence; both global symptoms and abdominal pain improve. Selective serotonin reuptake inhibitors (SSRIs) are of uncertain efficacy but anecdotally appear to be useful. Laxatives are not of proven efficacy in IBS. Loperamide improves diarrhea, but not abdominal pain in IBS. No drug is of proven efficacy for bloating. Acid suppression remains the mainstay of therapy for functional dyspepsia but the majority of patients do not have an adequate response. Promising drugs include new prokinetics for constipation-predominant IBS (e.g., tegaserod, a partial 5-HT4 agonist, prucalopride, a full 5-HT4 agonist, and dexloxiglumide, a cholecystokinin1 antagonist), agents for diarrhea-predominant IBS (e.g., 5-HT3 antagonists, alpha2 receptor agonists and corticotrophin receptor-1 antagonists), other visceral analgesics (e.g. tachykinin antagonists, opioid agonists) and in dyspepsia fundus relaxing agents (e.g., 5-HT1 agonists, tegaserod).

Journal Article↗
PubMed2002

Burden of illness in irritable bowel syndrome comparing Rome I and Rome II criteria.

OBJECTIVES: To evaluate the burden of illness in irritable bowel syndrome (IBS), in terms of resource utilisation (direct and indirect) and health-related quality of life (HR-QOL), in individuals with IBS who meet Rome I and Rome II criteria. METHODS: A cross-sectional study, carried out by personal interview, on a representative sample (n = 2000) of the Spanish population. Individuals with suspected IBS were identified via a screening question and subsequently given an epidemiological questionnaire to complete. The questionnaire collected information on IBS symptoms, resource utilisation, and HR-QOL [Medical Outcomes Study 36-item Short Form (SF-36)]. RESULTS: Sixty-five individuals met Rome II criteria for IBS, while 146 individuals met exclusively Rome I criteria. Of Rome II individuals, 67.7% had consulted some type of healthcare professional in the previous 12 months, compared with only 41.8% of those individuals meeting exclusively Rome I criteria (p vs 17.1%); 'drug consumption' (70.8 vs 45.2%); and 'reduced performance in main activity' (60 vs 27.4%). Compared with the general population, the study sample reported significantly worse HR-QOL scores in four dimensions of the SF-36 ('bodily pain', 'vitality', 'social functioning' and 'role-emotional'. Additionally, individuals meeting Rome II criteria reported worse HR-QOL scores than those individuals meeting exclusively Rome I criteria, especially in the 'bodily pain' and 'general health' dimensions. CONCLUSIONS: The burden of illness in IBS is important and correlated to the diagnostic criteria employed. Individuals who met Rome II criteria reported a higher level of resource utilisation and worse HR-QOL than individuals meeting exclusively Rome I criteria.

Adolescent↗
PubMed1993

Functional dyspepsia. Current treatment recommendations.

Symptoms of functional dyspepsia are frequent; the prevalence of dyspepsia (defined as pain or discomfort centred in the upper abdomen) in the general population approaches 25%. By definition, patients with functional dyspepsia do not have a structural or biochemical explanation for their symptoms. Disorders of function (e.g. delayed gastric emptying) are detectable in a proportion of patients but remain poorly understood. Nevertheless, the current rationale for drug treatment is based on altering pathophysiological mechanisms which are believed to be associated with the development of symptoms. Although the placebo response rates approach 60%, prokinetics, acid-suppressing agents and bismuth-containing compounds have been shown to be significantly better than placebo in reducing symptoms. Antacids are widely used, but no controlled study has been able to demonstrate a significant benefit over placebo. The efficacy of sucralfate is uncertain. Rational guidelines on which drug should be used for a given patient are lacking, although approaches based on symptom profiles have been proposed; the duration of treatment needed to achieve long-lasting relief of symptoms is also poorly defined. Identifying optimal treatment for the individual patient, therefore, continues to be largely a trial and error process. Further research efforts are needed to elucidate the pathophysiological basis of functional dyspepsia so that specific therapy can be tailored to underlying pathophysiological disturbances.

Cisapride↗