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Biomedical subjects

A G Fraser

Publications and source records attributed to A G Fraser.

At least 73 records · Page 4Linked to original sources
PubMed1996

Morning versus evening dosing of lansoprazole 30 mg daily on twenty-four-hour intragastric acidity in healthy subjects.

BACKGROUND: Morning dosing is usually recommended with proton pump inhibitors, but there are few data from 24-h intragastric acidity studies comparing times of dosing. METHODS: A double-blind, placebo-controlled study was performed on the seventh day of dosing to compare the effects of lansoprazole 30 mg given either in the morning or evening on 24-h intragastric acidity in 32 healthy volunteers. RESULTS: The median integrated 24-h intragastric acidity on the seventh day of morning dosing with lansoprazole 30 mg was decreased to 36% of the placebo value, compared with 42% for evening dosing. For each daytime meal-related interval, morning dosing was significantly more effective for controlling acidity, but there was no significant difference between the regimens during the night interval (23.00-08.00 h). CONCLUSIONS: These data favour morning dosing of lansoprazole 30 mg for routine use, but patients with mainly nocturnal symptoms may be best treated by evening dosing.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

Prevalence of Helicobacter pylori infection in different ethnic groups in New Zealand children and adults.

BACKGROUND: Helicobacter pylori infection is a major risk factor for peptic ulcer disease and gastric cancer. A study of patients with dyspepsia attending for gastroscopy showed significant differences in H. pylori seropositivity between ethnic groups. AIMS: To determine the prevalence of H. pylori in children and adults in the community in different ethnic groups and to identify risk factors for infection. METHODS: Serum samples (324) were randomly selected from a cross-sectional survey of 11-12 year old school children with a high proportion of Maori and Pacific Island groups. Serum samples (579) were randomly selected from a cross-sectional workforce survey of 5677 participants aged 40-64 years. Serum samples were tested for H.pylori IgG. RESULTS: The percentage seropositivity in 11-12 year old children was European 7%, Maori/part Maori 21%, all Pacific Island groups 48% and for the workforce survey 35.8%, 57.4% and 73.2% respectively. Compared with Europeans the increased relative risk of seropositivity for H.pylori in Maori and Pacific Island participants was significant after adjusting for age and socio-economic status (1.43 [1.13, 1.80] and 1.76 [1.43, 2.18]) respectively. The relative risk of H.pylori infection significantly increased with age, lower socio-economic status and lower household income, but was not significantly associated with gender, alcohol or cigarette use. CONCLUSIONS: The high seroprevalence of H.pylori in Maori and Pacific Island groups is consistent with the differences in incidence of gastric cancer. H.pylori continues to be a common infection in Maori and Pacific Island school children. Ethnicity appears to be a risk factor for H.pylori independent of socio-economic status.

Adult↗
PubMed1996

Double-blind, multicenter, placebo-controlled evaluation of clarithromycin and omeprazole for Helicobacter pylori-associated duodenal ulcer.

BACKGROUND: Eradication of Helicobacter pylori leads to faster ulcer healing and a significant decrease in ulcer recurrence. Clarithromycin is the most effective monotherapy for eradicating H. pylori from the gastric mucosa, and omeprazole frequently is used for the treatment of duodenal ulcer disease, prompting the interest to investigate rigorously the combination of clarithromycin and omeprazole for eradicating H. pylori. MATERIALS AND METHODS: The aim of this double-blind, randomized, multicenter (n = 30), multinational (n = 10) study was to compare clarithromycin and omeprazole with omeprazole monotherapy for the eradication of H. pylori from the gastric mucosa, endoscopic healing, and reduction of symptoms and ulcer recurrence in patients with active duodenal ulcer. Patients with active duodenal ulcer associated with H. pylori infection were randomized to receive omeprazole, 40 mg every morning for 14 days, with either clarithromycin, 500 mg, or placebo three times daily, which was followed by omeprazole, 20 mg every morning for 14 days. Patients underwent endoscopy before enrolling in the study, immediately after finishing treatment, and at 4- to 6-week and 6-month follow-up evaluations or at the recurrence of symptoms. RESULTS: Two hundred and eight patients with active duodenal ulcer associated with confirmed H. pylori infection were randomized to treatment with either clarithromycin and omeprazole (n = 102) or omeprazole and placebo (n = 106). Four to six weeks after treatment was completed, H. pylori was eradicated in 74% (95% confidence interval, 63.0%-82.4%) of patients receiving clarithromycin and omeprazole, compared with 1% (0.0%-6.2%) of patients receiving omeprazole monotherapy (p < .001). Clarithromycin resistance developed in eight patients treated with clarithromycin and omeprazole and in none given omeprazole and placebo. Ulcers, which were healed following treatment in more than 95% of study patients, recurred by the 6-month follow-up visit in 10% (5%-19%) of dual therapy recipients, compared with 50% (39%-61%) of those who took omeprazole alone (p < .001). CONCLUSION: Clarithromycin and omeprazole dual therapy is simple and well-tolerated and leads to consistently high eradication rates for patients with duodenal ulcer associated with H. pylori infection.

Adult↗
PubMed1996

Doppler analysis of pulmonary venous flow profiles in orthotopic heart transplant recipients: a comparison with mitral flow profiles and atrial function.

Previous Doppler studies of transmitral flow profiles in heart transplant recipients suggested left ventricular (LV) diastolic dysfunction. The influence of left atrial filling and emptying on mitral Doppler profiles in heart transplant recipients has not been studied systematically. In the present study, pulmonary venous flow profiles, mitral flow profiles, left atrial area change and mitral annulus motion were analyzed in 20 orthotopic heart transplant recipient and 20 control subjects by transthoracic and transesophageal echocardiography and Doppler. Mitral flow profiles revealed a "restrictive" pattern with a high early-to-late diastolic flow velocity ratio in transplant patients (2.16 +/- 0.52 vs. 1.30 +/- 0.25, p < 0.0001), which was mainly due to a reduced late diastolic maximum mitral flow velocity (32.6 +/- 8.3 vs. 51.6 +/- 12.4 cm/s, p < 0.0001). Left atrial area change (35.9 +/- 13.9 vs. 58.1 +/- 17.0%, p < 0.0006) and mitral annulus motion (9.2 +/- 3.3 vs. 12.2 +/- 2.0%, p < 0.05) were reduced in transplant recipients, compared to controls. Pulmonary venous flow parameters in transplant recipients were markedly altered during systole, when pulmonary venous flow parameters are influenced primarily by atrial function rather than by diastolic LV properties: peak systolic flow velocity (45.5 +/- 8.2 vs. 62.3 +/- 14.0 cm/s, p < 0.001), maximum flow velocity ratio (0.87 +/- 0.19 vs. 1.45 +/- 0.33), time velocity integral of pulmonary venous flow during systole (9.3 +/- 2.3 vs. 17.1 +/- 4.0 cm, p < 0.001) and the systolic fraction of the time velocity integral (52.6 +/- 10.8 vs. 68.5 +/- 6.8%, p < 0.001) were lower in heart transplant recipients than in controls. These findings are compatible with atrial dysfunction and reduced mitral annulus motion. The results of this study indicate that LV diastolic dysfunction is not the only possible cause of altered transmitral Doppler profiles in heart transplant recipients. Atrial abnormalities represent a major contributing factor to altered mitral and pulmonary venous flow patterns. Analysis of transmitral Doppler profiles alone are therefore not adequate for analysis of diastolic LV function in heart transplant recipients.

Adult↗
PubMed1995

Gastric persorption of bismuth from ranitidine bismuth citrate.

AIM: To determine whether bismuth penetrates the gastric mucosa after dosing with ranitidine bismuth citrate. METHODS: Twelve patients presenting with dyspepsia were randomized to receive either ranitidine bismuth citrate or placebo, 20-40 min prior to endoscopy. Biopsies were taken from four sites during endoscopy: the first and second parts of the duodenum, the antrum, and the body of the stomach. Biopsies were analysed by electron microscopy and X-ray microanalysis. RESULTS: Bismuth particles were found to be interposed between epithelial cells in the antral mucosa of three of eight patients who were dosed with ranitidine bismuth citrate. Columns of bismuth particles could be tracked down the lamina propria and were seen to be surrounding blood vessels. Bismuth particles were observed in the inter- and intra-cellular channels of the endothelial cells of the blood vessels in the lamina propria and also close to the luminal surface of the endothelial cell. This process of persorption was similar to that described in a previous report of electron microscopy appearances of the gastric antrum after dosing with tripotassium dicitrato bismuthate, but was quantifiably smaller and not observed in all the patients dosed with ranitidine bismuth citrate. No penetration of the mucosa by bismuth particles was seen in the body of the stomach or the duodenum. CONCLUSION: Penetration of bismuth particles into the gastric mucosa may occur after oral dosing with ranitidine bismuth citrate.

Adult↗
PubMed1995

Inter-individual and intra-individual variability of ethanol concentration-time profiles: comparison of ethanol ingestion before or after an evening meal.

1. The magnitude of the variability of ethanol absorption is an important factor for studies that seek to determine the significance of potential interactions between ethanol and drugs. The aim of this study was to determine the extent of inter- and intra-individual variability of ethanol concentration-time profiles in fasted and fed subjects. 2. Twenty-four healthy male subjects were randomized to receive ethanol 0.3 g kg-1 before an evening meal on two study days and ethanol 0.3 g kg-1 after an evening meal on two study days. Plasma ethanol concentrations were measured at intervals from 0-240 min. 3. There were significant differences in the mean area under the ethanol concentration-time curve (AUC), the mean peak ethanol concentration (Cmax), the mean ethanol elimination slope and the time to peak ethanol concentration between the fed and fasted subjects. There were no significant differences between the first and second study days for either fed or fasting subjects for all parameters. 4. There was no statistically significant difference in inter- or intra-subject variance between fed and fasted studies although the coefficients of variation (standard deviation expressed as a percentage of the mean) for the differences between the first and second study day were higher for fed studies. 5. The large inter- and intra-individual variability of alcohol absorption for both fasted and fed subjects must be considered in the design of alcohol-drug interaction studies.

Adult↗
PubMed1994

Effects of ranitidine 150 mg four times a day on 24-hour intragastric acidity and 24-hour plasma gastrin concentration.

Twenty-four-hour integrated intragastric acidity and 24-hr integrated plasma gastrin concentration was measured twice in 23 healthy male volunteers on the seventh day of oral dosing with placebo or ranitidine 150 mg four times a day. The study was a randomized, double-blind, placebo-controlled, two-way crossover investigation. The mean integrated 24-hr intragastric acidity during dosing with ranitidine 150 mg four times a day decreased to 32% of the placebo value (placebo 825 mmol/hr/liter; ranitidine 265 mmol/hr/liter). The mean integrated 24-hr plasma gastrin concentration during dosing with ranitidine 150 mg four times a day was 904 pmol/hr/liter compared with placebo (410 pmol/hr/liter)--an increase of 122%. The median number of hours of pH > 3 during dosing with placebo and with ranitidine 150 mg four times a day were 5 and 11 hr, respectively. Ranitidine 150 mg four times a day caused a significant decrease of mean integrated intragastric acidity for each meal-related interval and also during the night.

Adult↗
PubMed1994

Echocardiographic evidence of persistent pericardial effusion after open heart surgery.

Cross-sectional and M-mode echocardiography were used to review 33 patients 6-28 months (mean 19 months) after open heart surgery. Eleven patients had had echocardiographic signs of pericardial effusion during the first week after open heart surgery (Group A), and 22 had not (Group B). At review, pericardial effusion was found in 73% of subjects in Group A compared with 18% of those in Group B (P < 0.01). On average, posterior effusions were small (mean dimension in systole 0.9 cm) but they were detected reproducibly (interobserver agreement 97%). Anterior echo-free spaces (< 0.5 cm) were found frequently, but interobserver variation in their detection was high (agreement in 68%). Symptoms did not correlate with the presence of a late post-operative effusion but the groups were not matched for rhythm or ventricular function. Five patients in Group A had developed atrial fibrillation in association with their early post-operative effusion, and four of these had persisting atrial fibrillation at this review. These results suggest that echo-free spaces around the heart, suggestive of small pericardial effusions, may persist for many months after open heart surgery.

Cardiac Surgical Procedures↗
PubMed1994

Transesophageal echocardiographic monitoring of preoperative acute hypervolemic hemodilution.

BACKGROUND: Preoperative acute hypervolemic hemodilution is used in anesthesia to reduce the loss of blood cells during intraoperative bleeding. Indications for use of the technique might be broadened if it can be shown to be safe in older as well as younger patients. Few data are available describing heart function in humans subjected to hypervolemic hemodilution. METHODS: Nineteen anesthetized Jehovah's Witnesses (ages 22-70 yr) without evidence of heart disease had hypervolemic hemodilution before surgery in three stages, each consisting of an infusion of 500 ml dextran 40 (50 g/l) and 500 ml Ringer's lactate over a 10-min period. After each stage, the size and function of the left ventricle were recorded by transesophageal cross-sectional echocardiography in the short-axis view. Simultaneously heart rate, arterial blood pressure, pulmonary arterial and wedge pressures and cardiac output were recorded, to compare the echocardiographic and hemodynamic data. RESULTS: No complications occurred. Hypervolemic hemodilution resulted in an increased cardiac output by increasing the stroke volume from 48 ml in basal conditions to 67, 71, and 72 ml over the three stages, whereas heart rate did not increase. There was an initial increase in end-diastolic volume of the left ventricle, as assessed from the cross-sectional end-diastolic area from 12.9 to 15.5, 16.6, and 16.9 cm2 followed by a decrease in the in cross-sectional end-systolic area from 6.3 to 6.8, 6.0, and 5.7 cm2. The increase in wedge pressures (from 5.9 to 12.4, 17.9, and 22.6 mmHg) did not lead to progressive cardiac dilation. There was a curvilinear relation between wedge pressure and cross-sectional end-diastolic area. Stroke volume did not decrease, nor did cross-sectional end-systolic area increase; instead, a decrease in end-systolic area was a common observation. CONCLUSIONS: The described regimen of acute hypervolemic hemodilution is well tolerated during anesthesia by patients without heart disease and does not lead to cardiac failure. It leads to an increase in stroke volume that is generated initially from an increase in end-diastolic volume, followed in many patients by a decrease in end-systolic volume, the mechanism of which is as yet unclear.

Adult↗
PubMed1994

Effect of eradication of Helicobacter pylori on gastric epithelial cell proliferation.

BACKGROUND: Helicobacter pylori is associated with B-type gastritis, duodenal ulcer disease, and possibly gastric carcinoma. The object of this study was to assess the effect of eradication of H. pylori infection on gastric epithelial cell proliferation. METHODS: Gastric epithelial cell proliferation was assessed in 22 H. pylori-positive duodenal ulcer patients before and 6 weeks after 'triple therapy' with bismuth, tetracycline and metronidazole. Cell proliferation was studied either by immunostaining for the proliferating cell nuclear antigen (PCNA) or by a microdissection technique. RESULTS: Eradication was successful in 10 of the 22 H. pylori-positive patients. Treatment with 'triple therapy' resulted in a significant fall in the rate of gastric epithelial cell proliferation; this effect was seen in both the gastric body and antrum. There was a significant correlation between the number of PCNA-labelled cells and the histological grade of activity (neutrophil inflammation) (r = 0.49, P = 0.02); the same correlation was found for the number of mitoses per gland (r = 0.5, P = 0.02). There was no significant difference in the treatment effect for eradicated or non-eradicated patients or either the body or antrum. Six patients, who had at least one antral biopsy that showed evidence of focal intestinal metaplasia, had a higher rate of cell proliferation. CONCLUSIONS: The reduction in epithelial cell proliferation in the body and antrum after triple therapy is independent of successful eradication of H. pylori, and it may be due to an anti-inflammatory effect of triple therapy.

Adult↗
PubMed1994

Review article: gastro-oesophageal reflux and laryngeal symptoms.

There is some evidence from clinical, experimental and multiprobe ambulatory pH studies that gastro-oesophageal reflux is more common in patients with laryngeal symptoms and could potentially play a role in the causation of these symptoms. The proportion of unselected patients with laryngeal symptoms who have gastro-oesophageal reflux as the primary aetiology may be overestimated in some series. The symptom that has been most evaluated is hoarseness, but even for this symptom the proportion of patients who have significant reflux varies widely. There is even less agreement for other symptoms, and the data on globus sensation remains confused. It is likely that these patients present to ear, nose and throat (ENT) clinics because of the relative insensitivity of the oesophageal mucosa to acid exposure. Given the lack of specificity for routine diagnostic tests for gastro-oesophageal reflux, it is necessary to perform ambulatory pH monitoring for a secure diagnosis in these patients. Treatment studies have been surprisingly few and inadequate in design. It is suspected that there is a strong placebo response for these symptoms. No clear information on efficacy can be provided until placebo-controlled randomised studies are available.

Clinical Trials as Topic↗
PubMed1994

Transoesophageal echocardiography as the sole diagnostic investigation in patients with suspected thoracic aortic dissection.

OBJECTIVES: To assess the value and limitations of using transoesophageal echocardiography as the sole diagnostic test in patients with suspected thoracic aortic dissection. DESIGN: Retrospective data review over a two year period. SETTING: A regional cardiothoracic centre. PATIENTS: Data were compiled from admission records, surgical records, and lists of patients undergoing diagnostic investigations in the hospital. Patient's notes were used to identify presentation, management, and outcome. INTERVENTIONS: Patients were managed according to the policy of our unit, which is to treat patients with dissection affecting the ascending aorta by an operation. Patients with uncomplicated dissection sparing the ascending aorta are initially managed medically. MAIN OUTCOME MEASURES: In hospital and two year follow-up of patients who were investigated by transoesophageal echocardiography alone. RESULTS: Of 48 patients referred, 45 underwent transoesophageal echocardiography. Dissection was confirmed in 22 patients. Transoesophageal echocardiography showed the proximal extent of the dissection in 21/22 (96%) and only one patient required a further diagnostic investigation. Ten patients with dissection of the ascending aorta underwent graft replacement of the ascending aorta; operative mortality was 10% and their two year survival was 80%. Of the eight patients with dissection of the descending aorta, six were discharged home, and five were alive at two years. No patient without evidence of dissection on their initial transoesophageal echocardiographic examination required re-investigation into possible dissection in the two years after discharge. CONCLUSIONS: In patients with suspected thoracic dissection transoesophageal echocardiography rapidly and safely gives all the necessary diagnostic information. Further investigations, including coronary angiography, before surgery are unnecessary.

Adult↗
PubMed1993

Gastric acid secretion and intragastric acidity: measurement in health and disease.

Gastric acid secretion tests have limited use in clinical practice. For practical purposes, a pH measurement on a fasting gastric aspirate will provide strong evidence of the presence or absence of achlorhydria. Tests of gastric acidity, in particular 24-h acidity studies, have provided considerable insight into normal and abnormal gastric physiology, and have largely determined the dosing regimens for the management of acid-peptic diseases. Acid tests may be simple to perform, so much so that they have been suggested as 'practicals' for student teaching (Nicol et al, 1991). However, reproducible and meaningful results require careful attention to detail, and the appropriate mathematical analysis is still subject to some debate. It is important that the presentation of the data should allow the reader to assess the response over the 24-h period, and also the range of individual responses. Despite the many years of research into gastric acid secretion, only recently have the effects of age, sex, diet, smoking and mental stress been identified. In addition, many data need to be reviewed in the light of the effects of H. pylori infection on gastrin release. H2-receptor antagonists had been studied extensively before and since their first clinical use in 1974, but surprisingly only recently have the issues of tolerance and rebound been defined. The 24-h intragastric acidity profile remains an essential study before the start of clinical trials on any new drug to be used for the treatment of acid-peptic diseases.

Duodenal Ulcer↗
PubMed1993

Gastric secretion and peptic ulceration in cirrhosis.

Stomach function and secretions are altered significantly in patients with cirrhosis, both with or without portal hypertension. This review covers the abnormalities of gastric acid and pepsin secretion, and gastrin release. Histological and endoscopic changes, and the impaired cytoprotection associated with cirrhosis, are discussed in the context of abnormal gastric secretion. In addition, the symptomatology and association of H. pylori, and treatment of duodenal ulceration in cirrhosis are discussed. It is clear from this review that additional studies are needed to further understand gastric function in cirrhotic patients.

Female↗
PubMed1993

Evaluation of the polymerase chain reaction for detecting the urease C gene of Helicobacter pylori in gastric biopsy samples and dental plaque.

A polymerase chain reaction (PCR) assay with oligonucleotide primers homologous to a portion of the urease C gene of Helicobacter pylori was evaluated for specificity with pure DNA and biopsy material. The assay was used to test for the presence of the organism in dental plaque. The species specificity of detection was confirmed by ensuring that the primers did not amplify DNA extracts from H. cinaedi, H. felis, H. fennelliae, H. mustelae and H. nemestrinae. Sixty-two gastric biopsy samples collected from 14 patients (antrum, body and duodenal sites) were cultured and PCR was performed on the samples after culture. Primer sites were conserved in genomically diverse strains. Samples prepared by single-step heat lysis of bacterial cells and biopsy material did not inhibit PCR. The overall specificity was 96% irrespective of genotype. H. pylori was not cultured from dental plaque (15 patients), neither was H. pylori DNA detected by PCR in either urea breath test-positive or -negative individuals. The results showed that primer pair sequences within the urease C gene are conserved in most strains and provide an accurate basis for detecting H. pylori. As the PCR assay was not inhibited and did not yield false positive results with crude extracts from organisms or in the presence of biopsy material, its value as a diagnostic test was confirmed.

Base Sequence↗
PubMed1993

Effect of ranitidine bismuth citrate on postprandial plasma gastrin and pepsinogens.

Ranitidine bismuth citrate was compared with an equipotent dose of ranitidine, to determine whether the former, by an anti-Helicobacter pylori activity, would counteract the rise of gastrin resulting from ranitidine's gastric acid antisecretory activity. Twenty four men with duodenal ulcers were studied before and on the 8th day of dosing with either ranitidine bismuth citrate 800 mg twice daily or ranitidine 300 mg twice daily (double blind, randomised, parallel groups). Fasting and postprandial plasma gastrin and plasma pepsinogen I and II concentrations were measured, and a 13C-urea breath test was performed before and on the 8th day of dosing. The 13C-urea breath tests were positive in 21 patients before dosing and remained positive in nine of nine of the ranitidine dosed patients, whereas only two of 12 patients treated with ranitidine bismuth citrate remained positive. The expected rise in meal stimulated plasma gastrin with ranitidine was seen in the 12 patients who received ranitidine but, despite suppression of H pylori urease activity in 10 of 12 patients taking ranitidine bismuth citrate, there was no attenuation of the meal stimulated gastrin rise. There was no significant difference in the mean derived (4 hour) plasma pepsinogen I and II concentrations after dosing with ranitidine or ranitidine bismuth citrate.

Adult↗