Biomedical subjects

D Armstrong

Publications and source records attributed to D Armstrong.

At least 37 records · Page 2Linked to original sources

PubMed2005

Subarachnoid injection of Microfil reveals connections between cerebrospinal fluid and nasal lymphatics in the non-human primate.

Based on quantitative and qualitative studies in a variety of mammalian species, it would appear that a significant portion of cerebrospinal fluid (CSF) drainage is associated with transport along cranial and spinal nerves with absorption taking place into lymphatic vessels external to the central nervous system. CSF appears to convect primarily through the cribriform plate into lymphatics associated with the submucosa of the olfactory and respiratory epithelium. However, the significance of this pathway for CSF absorption in primates has never been established unequivocally. In past studies, we infused Microfil into the subarachnoid compartment of numerous species to visualize CSF transport pathways. The success of this method encouraged us to use a similar approach in the non-human primate. Yellow Microfil was injected post mortem into the cisterna magna of 6 years old Barbados green monkeys (Cercopithecus aethiops sabeus, n = 6). Macroscopic and microscopic examination revealed that Microfil was (1) distributed throughout the subarachnoid compartment, (2) located in the perineurial spaces associated with the fila olfactoria, (3) present within the olfactory submucosa, and (4) situated within an extensive network of lymphatic vessels in the nasal submucosa, nasal septum and turbinate tissues. We conclude that the Microfil distribution patterns in the monkey were very similar to those observed in many other species suggesting that significant nasal lymphatic uptake of CSF occurs in the non-human primate.

Animals↗

PubMed2005

The relationship between income and performance indicators in general practice: a cross-sectional study.

OBJECTIVE: To explore the relationship between the income of general practitioners (GPs) and the performance characteristics of their practices. DESIGN: Cross-sectional survey. SETTING: All practices (n = 166) in an inner city health authority, two years before the introduction of the new GP contract in April 2004 were studied. MAIN OUTCOME MEASURES: True income per GP was unavailable to us. Instead, the proxy measure - superannuable pay - was calculated (gross eligible income per GP minus the national average sum for GP expenses). Practice staff funding figures were also obtained. These two financial indicators were compared with practice characteristics and performance indicators. RESULTS: Data were available from 151 out of 166 practices. Based on regression analysis, larger list sizes and higher practice staff budgets predicted 31% of the variation in GP income (standardized beta = 0.66, P < 0.001; beta = 0.19, P = 0.02; respectively). Higher staff budgets were independently associated with better cervical smear and two-year-old vaccination rates (standardized beta = 0.24, P < 0.01; beta = 0.18, P = 0.03; respectively). No association was demonstrated between performance indicators and income. CONCLUSION: Under the previous contract, GPs were able to maximize their income by taking on more patients, whereas achievement of performance targets had very little impact on overall income. The opportunity costs of pursuing higher-quality care might have outweighed the modest financial rewards attached to performance targets. Provided rewards for good-quality care are sufficiently high, the new GP contract is likely to tip the balance in favour of generating earnings by improving the quality of clinical care. To deliver this care, as measured by available performance indicators, our findings imply that a greater investment in practice staff will be needed.

Cross-Sectional Studies↗

PubMed2004

Do physicians correctly assess patient symptom severity in gastro-oesophageal reflux disease?

BACKGROUND: The accuracy of physicians' assessment of the severity of gastro-oesophageal reflux disease is unclear. AIM: To correlate physician and patient assessment of gastro-oesophageal reflux disease severity and its response to treatment. METHODS: Adult uninvestigated gastro-oesophageal reflux disease patients (n = 217) completed symptom and health-related quality of life questionnaires at baseline and after treatment with esomeprazole 40 mg p.o. daily. Pearson coefficients quantified correlations between physician assessments and patient responses. RESULTS: At baseline, the strongest correlations were heartburn severity (0.31), overall symptom severity (0.44) and a domain of the quality of life in reflux and dyspepsia questionnaire (0.31) (P < 0.001). Correlations of change with treatment were greater than baseline correlations: heartburn (0.39), overall symptoms (0.50) and global rate of change -- stomach problems (0.72, all P < 0.001). The mean difference between the physicians' assessment of change and the patients' global rating of change was 0.20 (95% confidence intervals: 0.10-0.29) with physicians overestimating benefit. CONCLUSIONS: Correlations were often significant, although weak to moderate and better with symptom severity than with health-related quality of life instruments as well as with change after therapy than at baseline. Increasing attention to health-related quality of life may help physicians better understand patients' experience. In clinical trials, treatment success should be assessed by the patient as well as the physician.

Adolescent↗

PubMed2004

International validation of ReQuest in patients with endoscopy-negative gastro-oesophageal reflux disease.

BACKGROUND: Reflux Questionnaire (ReQuest), a newly developed gastro-oesophageal reflux disease-sensitive scale, can be used to reliably evaluate the effect of treatment on gastro-oesophageal reflux disease symptoms. AIM: International validation of this scale, in patients suffering from endoscopy-negative gastro-oesophageal reflux disease. METHODS: In this open, multicentre and multinational clinical trial 840 endoscopy-negative gastro-oesophageal reflux disease patients received pantoprazole 20 mg daily for 28 days. The long and short versions of ReQuest were completed both in the pre-treatment and treatment phases. For scale development an item reduction analysis was performed. Internal consistency, test-retest reliability and responsiveness were calculated for psychometric analysis. Construct validity was evaluated by comparison with the Gastrointestinal Symptom Rating Scale and the Psychological General Well-being questionnaire by means of correlation coefficients. RESULTS: Factor analyses confirmed the content validity of both long and short version of ReQuest. Psychometric calculations proved high internal consistency (Cronbach's alpha: 0.9), test-retest reliability [Intraclass Correlation Coefficient: 0.9 (long vs. long) and 0.8 (short vs. short)], and responsiveness (Responsiveness Index 320.3) of the scale, for which also good construct validity was achieved (correlation coefficient: Gastrointestinal Symptom Rating Scale -0.6; Psychological General Well-being -0.4). CONCLUSION: ReQuest proved valid, reliable, and responsive in this multinational clinical trial to evaluate treatment response in endoscopy-negative gastro-oesophageal reflux disease patients.

Adult↗

PubMed2004

The role of acid suppression in patients with endoscopy-negative reflux disease: the effect of treatment with esomeprazole or omeprazole.

BACKGROUND: Patients with endoscopy-negative reflux disease have reflux symptoms, mainly heartburn, but not mucosal breaks characteristic of erosive oesophagitis. Standard-dose proton pump inhibitors can provide symptom relief in endoscopy-negative reflux disease but the effect of greater acid suppression has not been studied. AIM: To test the hypothesis that esomeprazole produces heartburn resolution in a greater proportion of patients with ENRD than omeprazole. METHODS: Three multi-centre randomized, controlled, double-blind, 4-week acute treatment studies were conducted in endoscopy-negative reflux disease patients. In study A (n = 1282), patients received either esomeprazole 40 mg, esomeprazole 20 mg or omeprazole 20 mg daily; in studies B (n = 693) and C (n = 670) patients received either esomeprazole 40 mg or omeprazole 20 mg (B), and esomeprazole 20 mg or omeprazole 20 mg (C), respectively. RESULTS: Resolution of heartburn at 4 weeks (no heartburn symptoms during the last 7 days) was achieved in similar proportions of patients in each treatment arm in study A (esomeprazole 40 mg, 56.7%; esomeprazole 20 mg, 60.5%; omeprazole 20 mg, 58.1%), study B (esomeprazole 40 mg, 70.3%; omeprazole 20 mg, 67.9%) and study C (esomeprazole 20 mg, 61.9%; omeprazole 20 mg, 59.6%). There were no significant differences between treatment groups within each study. CONCLUSIONS: More than 60% of endoscopy-negative reflux disease patients reported heartburn resolution but, after 4 weeks of therapy, these proportions did not differ significantly between treatments.

Adult↗

PubMed2004

Evaluation of GERD symptoms during therapy. Part II. Psychometric evaluation and validation of the new questionnaire ReQuest in erosive GERD.

BACKGROUND/AIMS: Evaluation of the response of gastroesophageal reflux disease (GERD) symptoms to treatment would be facilitated by a brief, valid, reliable and responsive, self-assessed GERD-sensitive scale. We therefore developed the Reflux Questionnaire (ReQuest). This publication describes the psychometric evaluation and validation of ReQuest. METHODS: This second phase of development was based on data from a clinical trial of patients with erosive GERD who received pantoprazole 20 or 40 mg daily for 28 days and completed weekly the long, and daily the short version of ReQuest. The psychometric analyses of ReQuest included internal consistency, test-retest reliability and responsiveness. Construct validity was evaluated by comparison with the Gastrointestinal Symptom Rating Scale (GSRS) and the Psychological General Well-Being (PGWB) scale. RESULTS: Validation of ReQuest indicated very high internal consistency (Cronbach's alpha = 0.90) and test-retest reliability (intraclass correlation coefficient 0.94 (long-long) and 0.86 (short-short)). This was also the case for the two subscales ReQuest-GI and ReQuest-WSO with Cronbach's alpha coefficients of 0.84 and 0.81. Responsiveness was high with a responsiveness index of >0.8 at day 28. Construct validity was good. CONCLUSION: ReQuest is a highly reliable, valid and responsive self-assessment tool for evaluating treatment response in patients with erosive GERD, and can be applied daily.

Endpoint Determination↗

PubMed2004

Evaluation of GERD symptoms during therapy. Part I. Development of the new GERD questionnaire ReQuest.

BACKGROUND/AIMS: The changes in gastroesophageal reflux disease (GERD)-related symptoms on treatment are variously described, but currently available questionnaires have shortcomings. We therefore developed a self-assessment reflux questionnaire (ReQuest). This article describes the process of development and testing. MATERIALS AND METHODS: For the first version of ReQuest the symptom spectrum of GERD and the various symptom descriptions were investigated. The 67 identified symptom descriptions were condensed empirically into 6 dimensions, to which a 7th dimension on general well-being was added. The symptom burden of the dimensions was measured by frequency and/or intensity. ReQuest was translated into different languages and then tested in focus groups. The initial validation was based on data from a clinical trial of patients with erosive GERD, treated with pantoprazole 20 or 40 mg daily for 28 days. Factor analyses determined the contribution of each symptom to the different dimensions. Additionally, correlation analyses between the identified factors and the dimensions were performed. RESULTS: On the basis of factor analyses, ReQuest was reduced to a 60-item scale. The factors generated correlated strongly with the dimensions and confirmed the empirical process mathematically. CONCLUSION: ReQuest provides a valuable, self-assessment tool for evaluating the daily treatment response in patients with erosive GERD.

Adult↗

PubMed2004

Systematic review: do we need a new gastro-oesophageal reflux disease questionnaire?

BACKGROUND: Gastro-oesophageal reflux disease (GERD) is highly prevalent in Western countries. Because the majority of patients do not present with endoscopic abnormalities, the assessment of the symptom severity and quality of life, and their response to treatment, has become increasingly important. Self-assessed symptom questionnaires are now key instruments in clinical trials. AIM: To evaluate the validity of available GERD measurement tools. METHODS: An ideal GERD symptom assessment instrument, suitable as a primary end-point for clinical trials, should possess the following characteristics: (i) be sensitive in patients with GERD; (ii) cover the frequency and intensity of typical and atypical GERD symptoms; (iii) be multidimensional (cover all symptom dimensions); (iv) have proven psychometric properties (validity, reliability and responsiveness); (v) be practical and economical; (vi) be self-assessed; (vii) use 'word pictures' which are easy to understand for patients; (viii) respond rapidly to changes (responsiveness over short time intervals); (ix) be used daily to assess changes during and after therapy; and (x) be valid in different languages for international use. RESULTS: A literature review revealed five scales that met some of the above characteristics, but did not fulfil all criteria. CONCLUSION: There is a need for a new evaluative tool for the assessment of GERD symptoms and their response to therapy.

Dyspepsia↗

PubMed2004

Economic evaluation of Helicobacter pylori eradication in the CADET-Hp randomized controlled trial of H. pylori-positive primary care patients with uninvestigated dyspepsia.

BACKGROUND: Adult Helicobacter pylori-positive patients by 13C-urea breath test with uninvestigated dyspepsia symptoms were randomized to 1-week eradication treatment with omeprazole, metronidazole and clarithromycin (OMC) vs. omeprazole and placebo antimicrobials (OPP) in the Canadian Adult Dyspepsia Empiric Treatment-H. pylori-positive (CADET-Hp) study. AIM: To perform an economic evaluation of this 1-year study. METHODS: Following blind eradication treatment, family practitioners managed patients according to their usual practices. Health resource utilization information was collected prospectively. From the mean costs of the health resources consumed and the treatment outcomes, the incremental cost-effectiveness ratios and incremental net benefits of eradication treatment vs. OPP were determined. RESULTS: Eradication therapy significantly improved dyspepsia symptoms (treatment success: OMC, 50%; OPP, 36%; P = 0.02). The incremental cost-effectiveness ratio of OMC vs. OPP was - 387 Canadian dollars (CAD$) per treatment success (90% CI, - CAD$1707, CAD$607), indicating a lower cost with treatment success. The incremental net benefit analysis showed that H. pylori eradication was cost-effective if the willingness-to-pay value exceeded a nominal figure of CAD$100 from a health service perspective or CAD$607 from the societal perspective. CONCLUSION: In uninvestigated patients presenting with dyspepsia at the primary care level, eradication of H. pylori in those who are H. pylori positive leads to a cost-effective improvement in dyspepsia symptoms compared with a strategy of not eradicating H. pylori in these patients.

Adolescent↗

PubMed2004

Fast-tracking revisited: routine cardiac surgical patients need minimal intensive care.

OBJECTIVE: Following cardiac surgery, patients are transferred from the operating theatre to intensive care. This clinical environment has one nurse per patient and facilities for mechanical ventilation. Patients are kept in this setting until the following day. This practice has been challenged with early extubation of patients. At our institution we have established a fast-track policy including the following features: (1) patient selection; (2) operating list scheduling with fast-track patients first; (3) anaesthetic tailored to early extubation; (4) methodical procedure with warm cardiopulmonary bypass; (5) removal of the arterial line; (6) transfer from intensive care to a separate high dependency unit ('step-down') on the day of operation, where the ratio of nurse to patient is one to three and there are no ventilatory facilities and no invasive monitoring; or (7) to keep these patients on ICU but decrease the nurse to patient ratio. METHOD: The case notes of 572 patients who predominantly had myocardial revascularisation, undergoing this process from July 1996 to July 2000 at our institution were reviewed. RESULTS: Mean EUROSCORE for the study group was 1.42. The 30-day mortality rate for the study group was 0.34%, mean intensive care time was 5 h 52 min, mean time to extubation was 3 h 10 min, mean readmission rate to intensive care was 0.34% and mean hospital stay from day of operation (inclusive) was 5.65 days. This process increased our throughput by 14.6% (compared to standard practices). COMMENT: This study demonstrates that transfer of appropriate patients to a high dependency area from intensive care following cardiac surgery is safe. It allows intensive care beds to be used by more than one patient each day and allows significant cost savings by reducing the nursing ratio per patient.

Adult↗

PubMed2004

Review article: towards consistency in the endoscopic diagnosis of Barrett's oesophagus and columnar metaplasia.

Barrett's oesophagus is associated with severe reflux disease and is a risk factor for oesophageal adenocarcinoma. However, there is a lack of consensus on how to assess the presence and extent of Barrett's oesophagus in clinical practice. A diagnosis of Barrett's oesophagus is currently based on the recognition of an abnormal oesophageal mucosa at endoscopy. However, a diagnosis cannot be made solely on this basis, and a true diagnosis requires the identification of an area suspicious for columnar metaplasia at endoscopy, followed by histological confirmation. Currently, difficulties in the assessment of Barrett's oesophagus include a lack of consistent definitions of endoscopic landmarks (such as the gastro-oesophageal and squamo-columnar junctions), a lack of standardization of descriptions of the extent of Barrett's oesophagus, and limited communication between the endoscopist and the pathologist, which hampers accurate histological confirmation. It is therefore important to develop an endoscopic description of Barrett's oesophagus, with a clear definition of endoscopic landmarks, to determine, amongst other things, whether anti-reflux therapy produces regression or a reduction in the length of Barrett's oesophagus. With this background, a subgroup of the International Working Group on the Classification of Oesophagitis was charged with developing a simple, practicable classification system, suitable for use with standard endoscopes, which would be easy to apply in clinical practice and in large clinical studies. Described in this review are a series of propositions and an overview of the 'CM classification', developed by the International Working Group on the Classification of Oesophagitis, to facilitate the endoscopic description of Barrett's oesophagus. It is hoped that these propositions will be the first step in the development of standard endoscopic diagnostic criteria for Barrett's oesophagus, relevant to clinical practice and clinical research.

Barrett Esophagus↗

PubMed2004

Review article: gastric pH -- the most relevant predictor of benefit in reflux disease?

Summary In patients with gastro-oesophageal reflux disease, the pH of refluxed gastric contents has a direct bearing on disease severity and oesophageal damage. A pH of 4 has been defined as a threshold below which refluxed gastric contents become injurious to the oesophagus. Studies in patients with erosive oesophagitis have shown that the 8-week healing rates produced by acid suppressive therapy are related to the duration of time over a 24-h period that the intragastric pH > 4. The most effective agents, providing more hours with gastric pH > 4 and higher healing rates in erosive oesophagitis patients, are the proton pump inhibitors. The intragastric pH is often used to gauge the efficacy of acid suppressive therapies. There are several factors, however, that may affect the clinical relevance of such data, and these should be taken into account when comparing the effectiveness of different therapies. Firstly, because of inter-individual variation, studies comparing therapies should be of a crossover design, so that responses to therapy are measured in the same individuals. Secondly, the Helicobacter pylori status of the individual should be known, as H. pylori infection has been shown to increase intragastric pH readings when examining the effect of acid suppressive therapy. Other factors, such as positioning of the pH electrode and the duration of previous therapy, also need to be standardized when using intragastric pH to assess the efficacy of different therapies. Crossover studies comparing standard doses of different proton pump inhibitors have shown that esomeprazole 40 mg produces a significantly greater amount of time at intragastric pH > 4 on day 5 of treatment than standard doses of other proton pump inhibitors. The correlation between greater efficacy in acid suppression and clinical benefit is supported by the findings that esomeprazole 40 mg is the only proton pump inhibitor to provide greater 8-week healing rates in patients with erosive oesophagitis than both omeprazole and lansoprazole. These data all suggest strongly that intragastric pH monitoring is an effective surrogate marker and a relevant predictor of outcome in gastro-oesophageal reflux disease.

Esophagitis↗

PubMed2004

Oxidative stress and glucose levels in a population-based sample.

OBJECTIVES: To examine the relationship between markers of oxidative status and glucose on a population basis. STUDY DESIGN AND SETTING: We report here on a population-based sample of 1315 women and 981 men, aged 35-79 years, randomly selected from residents of Erie and Niagara Counties in western New York between 1996 and 1999. Thiobarbituric reactive substances (TBARS), erythrocyte glutathione (GSH) and plasma glutathione peroxidase (GSH-Px) were measured as markers of oxidative status. Study sample was categorized by quartiles of glucose, degree of abnormality of fasting glucose, and level of metabolic control in patients with diabetes. RESULTS: Men and women in the uppermost quartiles of glucose had higher levels of TBARS (men: Quartile 4 = 1.55 +/- 0.03, Quartile 1 = 1.36 +/- 0.03, women: 1.49 +/- 0.02, 1.30 +/- 0.02 nmol/ml) and lower levels of GSH (men: Quartile 4 = 1.57 +/- 0.03, Quartile 1 = 1.69 +/- 0.03, women: 1.71 +/- 0.03, 1.97 +/- 0.0 mmol/l packed RBCs). In women, compared with normal fasting glucose, impaired fasting glucose was associated with higher levels of TBARS (1.29 +/- 0.01 vs. 1.84 +/- 0.04 nmol/ml), lower levels of GSH (1.85 +/- 0.02 vs. 1.76 +/- 0.05 mmol/l packed RBCs), and higher GSH-Px activity (618.94 +/- 2.64 vs. 644.77 +/- 8.90 IU/l). In women, abnormal fasting glucose was associated with higher levels of TBARS (1.84 +/- 0.04 nmol/ml), lower levels of GSH (1.68 +/- 0.06 mmol/l packed RBCs), and higher levels of GSH-Px (647.72 +/- 9.87 IU/l) than normal or impaired fasting glucose. In men, abnormal fasting glucose was associated with higher TBARS (1.76 +/- 0.04 vs. 1.37 +/- 0.07 nmol/ml), and lower GSH (1.62 +/- 0.05 vs. 2.78 +/- 0.02 mmol/l packed RBCs), than normal fasting glucose. Poor metabolic control was associated with higher TBARS (men: 2.07 +/- 0.08 vs. 1.33 +/- 0.14 nmol/l, women: 2.02 +/- 0.09 vs. 1.35 +/- 0.18 nmol/l) and GSH-Px activity (men: 654.34 +/- 13.45 vs. 599.86 +/- 24.76, women: 660.61 +/- 13.25 vs. 579.42 +/- 27.42 IU/l). CONCLUSIONS: Glucose levels play a role in determining oxidative status in a population sample. The balance between oxidative and antioxidant processes appears to be sensitive to glucose levels with moderate elevations of glucose affecting the oxidative status.

Aged↗

PubMed2004

Symptom evaluation in reflux disease: workshop background, processes, terminology, recommendations, and discussion outputs.

There has been no published indepth systematic evaluation of the best approaches to symptom evaluation in gastro-oesophageal reflux disease (GORD). A two day international multidisciplinary workshop was therefore held in Marrakech, Morocco, in September 2002 to address these issues. The aim of the workshop was to critically review the data regarding the reliability, processes, and priorities for symptom evaluation in GORD patients. The workshop was designed to give outputs that could be readily reported and to arrive at specific recommendations on best practice in symptom evaluation in reflux disease.

Adenocarcinoma↗

PubMed2004

Cystic fibrosis patients and families support cross-infection measures.

A clonal strain of Pseudomonas aeruginosa (PA) was isolated in 1999 at the Royal Children's Hospital, Melbourne, Australia, after five unrelated children with cystic fibrosis (CF) died from severe lung disease aged <5 yrs. Subsequently, more than half of the patients in the clinic with PA were found to harbour this strain, and segregation measures were instituted at the hospital to prevent further spread. The aim of this study was to assess CF parent and patient responses to the segregation measures to determine overall support. A questionnaire was sent out to the families of 291 CF children treated at the centre. A 65% response rate was obtained. The majority of parents (85%) and patients > or=12 yrs old (63%) were positive about the segregation measures instituted. A total of 11% of parents and 25% of patients were unsure, and 4% of parents and 12% of children gave negative responses. Those who were not happy listed reasons such as concerns about the emotional impact of not socialising with other CF children, inconclusive evidence about person-person spread of infection and feelings of alienation created in the clinic by the separation. In conclusion, the majority of responding cystic fibrosis patients and their families understand and are supportive of infection control measures instituted at the Royal Children's Hospital, Melbourne, Australia.

Adult↗

PubMed2004

Agouti-related protein (83-132) is a competitive antagonist at the human melanocortin-4 receptor: no evidence for differential interactions with pro-opiomelanocortin-derived ligands.

Interactions between pro-opiomelanocortin (POMC)-derived peptides, agouti-related protein (AGRP) and the melanocortin-4 receptor (MC4-R) are central to energy homeostasis. In this study we have undertaken comprehensive pharmacological analysis of these interactions using a CHOK1 cell line stably transfected with human MC4-R. Our main objectives were (1) to compare the relative affinities and potencies of POMC-derived peptides endogenously secreted within the hypothalamus, (2) to investigate the potency of AGRP(83-132) antagonism with respect to each POMC-derived peptide and (3) to determine whether AGRP(83-132) and POMC-derived peptides act allosterically or orthosterically. We have found that beta melanocyte-stimulating hormone (betaMSH), desacetyl alpha MSH (da-alphaMSH) and adrenocorticotrophic hormone all have very similar affinities and potencies at the MC4-R compared with the presumed natural ligand, alphaMSH. Moreover, even MSH precursors, such as beta lipotrophic hormone, showed significant binding and functional activity. Therefore, many POMC-derived peptides could have important roles in appetite regulation and it seems unlikely that alphaMSH is the sole physiological ligand. We have shown that AGRP(83-132) acts as a competitive antagonist. There was no significant difference in the potency of inhibition by AGRP(83-132) or agouti(87-132) at the MC4-R, regardless of which POMC peptide was used as an agonist. Furthermore, we have found that AGRP(83-132) has no effect on the dissociation kinetics of radiolabelled Nle4,D-Phe7 MSH from the MC4-R, indicating an absence of allosteric effects. This provides strong pharmacological evidence that AGRP(83-132) acts orthosterically at the MC4-R to inhibit Gs-coupled accumulation of intracellular cAMP.

Agouti-Related Protein↗

PubMed2003

Oral esomeprazole vs. intravenous pantoprazole: a comparison of the effect on intragastric pH in healthy subjects.

BACKGROUND: Intravenous (IV) proton-pump inhibitor therapy is used in patients who cannot take oral medications or require greater acid suppression. Oral esomeprazole produces greater acid suppression than oral pantoprazole; however, no comparative data exist for oral esomeprazole and i.v. pantoprazole. AIM: To compare acid suppression (time with pH>3.0, 4.0, 5.0 and 6.0) produced by standard doses of oral esomeprazole and i.v. pantoprazole in healthy subjects. METHODS: A randomized, two-way crossover study in 30 subjects receiving oral esomeprazole (40 mg o.d.) or i.v. pantoprazole (40 mg o.d.) for 5 days followed by a 2-week washout period before the second 5-day drug administration period using the crossover drug regimen. RESULTS: Oral esomeprazole produced greater acid suppression than i.v. pantoprazole on day 1 [pH>3.0 (56.9%, 35.8%; P<0.001), pH>4.0 (43.4%, 25.0%; P<0.001) and pH>5.0 (28.7%, 15.6%; P<0.001)] and on day 5 [pH>3.0 (70.4%, 45.9%; P<0.001), pH>4.0 (59.2%, 33.9%; P<0.001), pH>5.0 (45.5%, 23.9%; P<0.001) and pH>6.0 (19.6%, 12.6%; P=0.045)]. The adverse event profiles indicated both treatments to be safe and well tolerated. CONCLUSIONS: In healthy subjects, esomeprazole, 40 mg o.d. dispersed in water, produces greater acid suppression than pantoprazole 40 mg i.v. o.d. after 1 and 5 days of medication.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2003

The prevalence of clinically significant endoscopic findings in primary care patients with uninvestigated dyspepsia: the Canadian Adult Dyspepsia Empiric Treatment - Prompt Endoscopy (CADET-PE) study.

BACKGROUND: Uninvestigated dyspepsia is common in family practice. The prevalence of clinically significant upper gastrointestinal findings (CSFs) in adult uninvestigated dyspepsia patients, and their predictability based on history, is unknown. METHODS: Prompt endoscopy was performed within 10 days of referral, in 1040 adult patients presenting with uninvestigated dyspepsia at 49 Canadian family practitioner centres. Subsequent management strategies during a 6-month follow-up period were determined by the individual family practitioners. RESULTS: CSFs were identified in 58% (603/1040) of patients. Erosive oesophagitis was most common (43%; N = 451); peptic ulcer was uncommon (5.3%; N = 55). Alarm symptoms were uncommon (2.8%; N = 29). Most patients had at least three dyspepsia symptoms, more than 80% had at least six, and approximately half had eight or more. Based on the dominant symptom, 463 (45%) patients had ulcer-like, 393 (38%) had reflux-like and 184 (18%) had dysmotility-like dyspepsia. The patients' dominant symptom was not predictive of endoscopic findings. Oesophagitis was more common in those with dominant reflux-like symptoms and was the most common finding in all subgroups. The prevalence of gastroduodenal findings was similar in all symptom subgroups. Helicobacter pylori (H. pylori) infection (30%; 301/1013) was associated with gastroduodenal findings. CONCLUSIONS: Dyspepsia subclassifications, based on dominant symptom, are of limited value in predicting the presence and nature of CSFs. Oesophagitis was by far the most common diagnosis (43% of patients). CSFs were common in uninvestigated dyspepsia patients and their nature suggests patients could be initially treated effectively, without endoscopy, using empirical acid suppressive therapy.

Adolescent↗