Biomedical subjects

A G Fraser

Publications and source records attributed to A G Fraser.

At least 55 records · Page 3Linked to original sources

PubMed1999

Gastric juice ascorbic acid is related to Helicobacter pylori infection but not ethnicity.

BACKGROUND: Maori and Pacific Island ethnic groups in New Zealand have a high risk for gastric cancer. Low levels of gastric juice ascorbic acid (vitamin C) have been suggested to be a risk factor for gastric cancer. Previous studies have shown that gastric juice ascorbic acid may be independently associated with both ethnicity and Helicobacter pylori infection. This study aimed to examine the interrelationship between H. pylori and ethnicity in New Zealand. METHODS: Gastric juice was collected into 70% perchloric acid preservative and stored at -80 degrees C. Ascorbic acid was analysed by high-performance liquid chromatography using ion-pair chromatography and electrochemical detection. Inflammation and atrophy was graded from biopsies from multiple sites in the antrum and body. Gastric juice was collected from 89 patients during routine endoscopy. RESULTS: There was a wide range of measured gastric juice ascorbic acid from 0.001 to 410 microg/mL. The median concentration of ascorbic acid for H. pylori-negative patients was 1.78 microg/mL (n = 57) and 0.12 microg/mL (n = 32) for H. pylori-positive patients (P = 0.001). Gastric juice ascorbic acid concentration was not associated with age, endoscopic diagnosis or intestinal metaplasia, but was significantly associated with the degree of acute inflammation (P = 0.01) and the presence of atrophy (P = 0.04). The median ascorbic acid concentration for European patients was 0.92 microg/mL (n = 44) and 0.09 microg/mL (n = 38) for Maori and Pacific Island ethnic groups combined (P = 0.1). Multiple step-wise regression analysis showed that only H. pylori infection was a significant factor for predicting ascorbic acid concentrations (r2 = 0.12). CONCLUSIONS: This study has confirmed that gastric juice ascorbic acid concentration is lower in the presence of H. pylori infection.

Adult↗

PubMed1999

Mobile echoes on prosthetic valves are not reproducible. Results and clinical implications of a multicentre study.

AIMS: To test the hypothesis that inter-observer variability accounts for the wide variation in reported prevalences of fibrin strands on prosthetic heart valves and to develop criteria for their identification and reporting. METHODS AND RESULTS: A videotape with 30 sequences of prosthetic heart valves imaged by transoesophageal echocardiography and showing abnormalities such as strands, microbubbles, and spontaneous echocardiographic contrast, was assessed in 13 European and three American centres. There were three duplicated examples, unbeknown to the observers. Definitions and reported prevalence rates of the abnormalities were analysed, and inter- and intra-observer agreement estimated with the kappa statistic. Mobile echoes were identified in 40 to 80% of the sequences on the tape. The reported prevalence of mobile echoes correlated with the time spent reporting the tape. There was moderate inter-observer agreement for the identification of any mobile echoes (kappa = 0.38), but no agreement for their labelling (kappa = 0.22), in spite of similar definitions. Intra-observer reproducibility was good (agreement in 76% of the reduplicated sequences). CONCLUSIONS: The true prevalence and potential significance of mobile echoes on prosthetic heart valves cannot be assessed unless inter-observer consensus on echocardiographic criteria for identifying such echoes is reached.

Adult↗

PubMed1999

Helicobacter pylori treatment and antibiotic susceptibility: results of a five-year audit.

BACKGROUND: Helicobacter pylori eradication treatment has been a rapidly evolving field. Audit of treatment results provides reassurance that trial data can be translated into routine clinical practice. METHODS: Data were collected prospectively over five years. Patients were given four different treatment regimens over the audit period 'standard' triple therapy, two types of clarithromycin-based treatment or ranitidine, amoxycillin and metronidazole. Eradication was proven by a urea breath test at least four weeks after completing treatment. RESULTS: Eradication treatment for H. pylori was given to 665 patients; 89% had follow-up data. H. pylori eradication was significantly associated with treatment type (p<0.0001) and smoking (p=0.04) by univariate analysis, but was not associated with sex, age, alcohol consumption, endoscopic diagnosis, recent treatment with anti-secretory drugs or NSAIDs. By logistic regression analysis, only treatment type was significant (p=0.0001). H. pylori culture and sensitivities were available for 255 patients. Metronidazole resistance was shown for 84 isolates (32%) and clarithromycin resistance for 18 isolates (6.8%). Metronidazole resistance was significantly associated with younger age (p=0.02), ethnicity (p=0.02), female sex (p=0.02), and year of endoscopy (p=0.04), but was not associated with clarithromycin resistance. Clarithromycin resistance was not associated with age, sex, or ethnicity. Metronidazole resistance significantly affected H. pylori eradication for regimens containing metronidazole without clarithromycin. Eradication with metronidazole without clarithromycin was achieved in 90% of sensitive strains but only 55% of resistant strains (p<0.001). Metronidazole resistance was not significantly associated with treatment failure when metronidazole was combined with clarithromycin. Eradication with metronidazole and clarithromycin was achieved in 86% of sensitive strains and 78% of resistant strains (p=0.42). CONCLUSION: Treatment type and antibiotic susceptibility are the most important determinants of treatment success.

Adolescent↗

PubMed1999

Delays by patients in seeking treatment for acute chest pain: implications for achieving earlier thrombolysis.

A study was set up to identify why patients delay seeking medical assistance after myocardial infarction. The study was performed in 100 consecutive patients with suspected acute myocardial infarction admitted to either the University Hospital of Wales, Cardiff, UK, or the Royal Jubilee Hospital, Victoria, British Columbia, Canada (50 patients from each centre). The main outcome measure was the delay from the onset of symptoms to admission to hospital. The mean total delay before admission was 385 minutes (SEM 45). The mean delay incurred by the patient in seeking assistance was 172 minutes (SEM 27), representing 45% of the total. Delay was longer in patients with crescendo angina and shorter in those later confirmed to have myocardial infarction. Patients with prior ischaemic heart disease (74% of patients) presented later than those with no such history. No other demographic or clinical factors predicted early or late presentation. Delays in seeking medical assistance after the onset of severe chest pain contribute significantly to total delays in patients' hospital admission and thrombolysis. The unexpected observation that patients with known ischaemic heart disease delay longer before seeking help in spite of their frequent contact with doctors, suggests that opportunities for educating patients are being wasted. Major efforts are needed to understand and modify behaviour of patients with chest pain to further reduce delays in treatment.

Adult↗

PubMed1998

Can the urea breath test for H.pylori replace endoscopy for the assessment of dyspepsia in primary care?

AIMS: The urea breath test may have value in the initial assessment of dyspepsia in primary care. This pilot study tracks patient and general practitioner behaviour which cannot be predicted with modelling studies. METHODS: The urea breath test was made available over a period of 18 months. The test was requested when general practitioners would normally have used a trial of medication or referred for endoscopy. Patients with a positive urea breath test had early endoscopy before treatment. Patients with a negative urea breath test were treated according to symptom response. A follow-up questionnaire was given 6-24 months after the urea breath test. RESULTS: Urea breath tests were requested on 249 patients; clinical notes and follow-up interview data were available for 207 patients (83%). The urea breath test was positive for 89 patients (43%); 70 were referred for endoscopy and peptic ulcer disease was found in 33 (47%). The urea breath test was negative for 118 patients; 14 were follow-up tests after previous H.pylori treatment. For the 104 patients with dyspepsia, a negative test and no previous treatment, 42% had 1 or more previous investigations for dyspepsia and 66% had dyspepsia symptoms for more than one year. During follow-up, 21 patients had endoscopy. Dyspepsia symptom scores were significantly lower at follow-up (p < 0.01). Using a global assessment, 66% had fewer symptoms, 22% same and 12% had more symptoms. The symptom improvement was greater if the duration of symptoms was less than one year (p < 0.05). Medication use did not change significantly. Twelve patients were dissatisfied with management; most of these would have preferred endoscopy. CONCLUSIONS: A negative urea breath test appears to have some reassurance value. The use of the urea breath test as initial assessment for dyspespia may prevent the need for some endoscopy. Further controlled studies of breath testing compared with early endoscopy are required.

Adult↗

PubMed1998

Periaortic fat pad mimicking an intramural hematoma of the thoracic aorta: lessons for transesophageal echocardiography.

We report a patient whose clinical and echocardiographic findings were compatible with a diagnosis of aortic intramural hematoma, but magnetic resonance imaging demonstrated a prominent and localized periaortic deposit of fat as the cause of the transesophageal echocardiographic appearance. This is a significant caveat that must be borne in mind when interpreting echocardiographic images obtained in patients with suspected intramural aortic hematomas.

Adipose Tissue↗

PubMed1998

Follow up after successful eradication of Helicobacter pylori: symptoms and reinfection.

The important long-term outcomes after Helicobacter pylori eradication are the proportion of patients with continuing symptoms, and the rate of recrudescence of the infection. Patients with proven H. pylori infection prior to treatment and a negative urea breath test at least 4 weeks after completing treatment were invited to return for a further urea breath test and a questionnaire. There were 167 patients and the mean interval since the post-treatment urea breath test was 16 months. The endoscopic diagnoses were duodenal ulcer 72, duodenitis 17, gastric ulcer 26, normal or oesophagitis 52. The ethnic groups were European 86, Maori 25, Pacific Island 28 and other ethnic groups 28. Ten patients (6%) had a positive urea breath test at follow up. The proportion of patients showing recrudescence of H. pylori was related to the delta value (delta) of the post-treatment urea breath test: delta 0-2, five of 146 (3.4%); delta 2-3, two of 18 (11%); and delta 3-4, three of five (60%). A symptom questionnaire was given to 147/157 patients with a persistently negative breath test; 60 had no symptoms, 31 had heartburn, 30 had epigastric pain, 15 had both heartburn and epigastric pain, and 11 had nausea or other symptoms. There were fewer symptoms in patients with gastric ulcer (GU) compared with patients with duodenal ulcer (DU) and non-ulcer patients. Twenty-four patients (16%) were taking H2-antagonists (including seven DU and five GU), 15 were taking antacids and four were taking omeprazole. There was no difference in medication use between diagnostic groups. Eighteen of the 46 patients (39%) with heartburn stated that this was a new symptom. Heartburn was a common symptom for duodenal ulcer patients after eradication (24/74, 32%). A second urea breath test 6-12 months after eradication is required to definitely prove eradication. Patients with a breath test delta value of 2-4 should have a repeat urea breath test.

Anti-Bacterial Agents↗

PubMed1998

Intestinal metaplasia subtypes and Helicobacter pylori infection: a comparison of ethnic groups in New Zealand.

Gastric cancer is two to four-fold more common in Maori and Pacific Island ethnic groups compared with Europeans. This study aimed to determine if intestinal metaplasia was more common in these ethnic groups. Patients attending for endoscopy for dyspepsia had six biopsies to determine the presence of Helicobacter pylori by at least two of the following tests: rapid urease test, 13C urea breath test, culture of histology and the presence, extent and subtypes of intestinal metaplasia. Biopsies were taken from 158 patients: Europeans (42%), Maori (23%), Pacific Islanders (35%). Helicobacter pylori and intestinal metaplasia were detected in 88 and 60% of Maori/Pacific Island patients, respectively, and 47 and 29% of Europeans, respectively. Type I intestinal metaplasia was detected in 43% of all patients, type II (26%) and type III (7.0%). The mean age of Maori/Pacific Island patients with intestinal metaplasia and type III intestinal metaplasia was 53 and 51 years respectively, compared with Europeans aged 65 and 72 years. Univariate analysis showed that intestinal metaplasia was associated with ethnicity and H. pylori (P < 0.001) but not age, smoking, endoscopic diagnosis or gender. Intestinal metaplasia is more common and occurs at an earlier age in Maori and Pacific Island patients.

Adult↗

PubMed1998

Is there an interaction between H2-antagonists and alcohol?

H2-antagonists are commonly prescribed drugs and alcohol use is widespread in the community. Any possible interaction may be important because of the frequent co-administration of both drugs and the potential for unexpected impairment of pyschomotor function, in particular, driving skills. Hepatic ADH is the major site of alcohol metabolism. ADH is also found in the stomach, but it is uncertain whether gastric ADH is able to metabolise a significant amount of alcohol in vivo. Significant first-pass metabolism can be demonstrated at lower doses of alcohol, and if alcohol is given after meals. Varying degrees of extraction of alcohol from the portal circulation probably explains the data regarding first pass metabolism rather than gastric metabolism by gastric ADH. H2-receptor antagonists inhibit gastric ADH activity to a variable extent. If gastric metabolism of alcohol is negligible then this inhibition has no relevance. Given the uncertainty regarding a mechanism of interaction, only carefully conducted studies in controlled environments will answer the question. The large inter-subject variability of alcohol absorption means that any study which seeks to determine the effect of an H2-receptor antagonist on ethanol metabolism must have sufficient numbers. A cross-over design, with each subject acting as his own control, is preferable to avoid ascribing an effect to treatment rather than to chance. The alcohol dosing studies are reviewed and the results summarised according to dose of alcohol given. At a dose of 0.15 g/kg of alcohol, four commonly used H2-antagonists may cause a small increase in blood alcohol concentrations in certain conditions. This absolute increase is very small. The magnitude of effect is far less than the effect of taking a meal before alcohol. At doses of 0.3 g/kg and above the majority of evidence favours no interaction between H2-antagonists and alcohol. There is no interaction at doses that would be expected to impair psychomotor skills (above 25 mg/dl). There remains a question regarding the cumulative effect of repeated small doses of alcohol and further studies are required. The relationship between ethanol absorption and gastric emptying raises the possibility that the effects of H2-receptor antagonists observed at very low doses of alcohol may be due to the acceleration of gastric emptying by these drugs. This is an attractive hypothesis that explains many aspects of the debate, but studies of the effect of H2-antagonists on gastric emptying have been conflicting.

Alcohol Drinking↗

PubMed1997

drICE is an essential caspase required for apoptotic activity in Drosophila cells.

Caspases are involved in the execution of cell death in all multicellular organisms so far studied, including the nematode worm, fruit fly and vertebrates. While Caenorhabditis elegans has only a single identified caspase, CED-3, whose activity is absolutely required for all developmental programmed cell deaths, most mammalian cell types express multiple caspases with varying specificities. The fruit fly Drosophila melanogaster is genetically tractable, less complex than vertebrates and possesses two known caspases, DCP-1 and drICE. The fly may therefore provide a good model system for examining the hierarchy and relative roles of individual caspases in the execution of apoptosis. We have examined the role of drICE in in vitro apoptosis of the D.melanogaster cell line S2. We show that cytoplasmic lysates made from S2 cells undergoing apoptosis induced by either reaper (rpr) expression or cycloheximide treatment contain a caspase activity with DEVD specificity which can cleave p35, lamin DmO, drICE and DCP-1 in vitro, and which can trigger chromatin condensation in isolated nuclei. Using antibodies specific to drICE, we show that immunodepletion of drICE from these lysates is sufficient to remove most measurable in vitro apoptotic activity, and that re-addition of exogenous drICE to such immunodepleted lysates restores apoptotic activity. We conclude that, at least in S2 cells, drICE can be the sole caspase effector of apoptosis.

Amino Acid Sequence↗

PubMed1997

Identification of a Drosophila melanogaster ICE/CED-3-related protease, drICE.

Cysteine proteases of the ICE/CED-3 family (caspases) are required for the execution of programmed cell death (PCD) in a wide range of multicellular organisms. Caspases are implicated in the execution of apoptosis in Drosophila melanogaster by the observation that expression of baculovirus p35, a caspase inhibitor, blocks cell death in vivo in Drosophila. We report here the identification and characterization of drICE, a D. melanogaster caspase. We show that overexpression of drICE sensitizes Drosophila cells to apoptotic stimuli and that expression of an N-terminally truncated form of drICE rapidly induces apoptosis in Drosophila cells. Induction of apoptosis by rpr overexpression or by cycloheximide or etoposide treatment of Drosophila cells results in proteolytic processing of drICE. We further show that drICE is a cysteine protease that cleaves baculovirus p35 and Drosophila lamin DmO in vitro and that drICE is expressed at all the stages of Drosophila development at which PCD can be induced. Taken together, these results strongly argue that drICE is an apoptotic caspase that acts downstream of rpr. drICE is therefore the first unequivocal link between the molecular machinery of Drosophila cell death and the conserved machinery of Caenorhabditis elegans and vertebrates. Identification of drICE should facilitate the elucidation of upstream regulators and downstream targets of caspases by genetic screening.

Amino Acid Sequence↗

PubMed1997

Dynamic obstruction of the external iliac artery in endurance athletes and its relationship to endothelial function: the case of a long distance runner.

There have been recent reports of exercise induced claudication in endurance trained athletes attributed to narrowing of the external iliac artery. Most patients have been competitive cyclists, and intimal hyperplasia has been cited as the cause. The case is reported here of a long distance runner who presented with similar symptoms.

Adult↗

PubMed1997

Pharmacokinetic interactions between alcohol and other drugs.

The frequent use of alcohol (ethanol) together with prescription drugs gives any described pharmacokinetic interaction significant clinical implications. The issue is both the effect of alcohol on the pharmacokinetics of various drugs and also the effect of those drugs on the pharmacokinetics of alcohol. This review discusses these pharmacokinetic interactions but also briefly describes some other effects of alcohol that are clinically relevant to drug prescribing. The use of several different study designs may be required before we can confidently state the presence or absence of any alcohol-drug interaction. Short term administration of alcohol in volunteers is the most common study design but studies of social drinking and prolonged moderate alcohol intake can be important in some situations. Community-based studies may illustrate the clinical relevance of any interaction. Alcohol can affect the pharmacokinetics of drugs by altering gastric emptying or liver metabolism (by inducing cytochrome P450 2E1). Drugs may affect the pharmacokinetics of alcohol by altering gastric emptying and inhibiting gastric alcohol dehydrogenase. The role of gastric alcohol dehydrogenase in the first-pass metabolism of alcohol is reviewed in this article and the arguments for and against any potential interaction between alcohol and H2 receptor antagonists are also discussed. The inhibition of the metabolism of acetaldehyde may cause disulfiram-like reactions. Pharmacodynamic interactions between alcohol and prescription drugs are common, particularly the additive sedative effects with benzodiazepines and also with some of the antihistamine drugs; other interactions may occur with tricyclic antidepressants. Alcohol intake may be a contributing factor to the disease state which is being treated and may complicate treatment because of various pathophysiological effects (e.g. impairment of gluconeogenesis and the risk of hypoglycaemia with oral hypoglycaemic agents). The combination of nonsteroidal anti-inflammatory drugs and alcohol intake increases the risk of gastrointestinal haemorrhage.

Acetaldehyde↗

PubMed1996

Eradication treatment for Helicobacter pylori in general practice.

AIMS: To identify patients with a past history of peptic ulcer and to treat Helicobacter pylori infection if confirmed. METHODS: Patient records from 6.5 full-time equivalent general practitioners were reviewed to record prescribing of H2-receptor antagonists in the last year and to review previous upper gastrointestinal investigations. RESULTS: Two hundred and sixty-seven patients had used H2-receptor antagonists in the previous year. The indications for use were peptic ulcer 25%, reflux 21%, empiric treatment for dyspepsia 39% and dyspepsia with a normal investigation 15%. Short-term prescribing was common (52% of patients treated for 1-2 months only) and of these patients 50% had undiagnosed dyspepsia. The most common indication for long-term prescribing (6 months or more) was peptic ulcer (46%). The records of 96 patients with peptic ulcer were identified; 50 were traced and considered for recall and a 13C urea breath test for Helicobacter pylori. Thirty-eight patients agreed to a breath test; 23 were positive (60.5%). Follow up breath test was negative following eradication treatment in 16 of 22 treated patients (73%). CONCLUSION: Patients with peptic ulcer disease can be recalled using general practice case notes and treated with antibiotic treatment. The majority of H2-receptor antagonist use is for indications other than peptic ulcer disease.

Aged↗

PubMed1996

An audit of low dose triple therapy for eradication of Helicobacter pylori.

AIMS: Standard triple therapy remains the recommended first line treatment for Helicobacter pylori in New Zealand. The real eradication rate achieved in busy hospital clinics may be different from data obtained from clinical trials outside of New Zealand. METHODS: One hundred and thirty patients with proven H pylori infection (by at least two tests) were treated with low dose triple therapy (DeNol 1 qid, tetracycline 250 mg qid and metronidazole 200 mg qid for 2 weeks; dosing with meals and at night); 83 were given a standard prescription for triple therapy (dispensed in bottles) and 47 were given a medication pack with times of dosing clearly marked. Eradication was proven by a negative 13C urea breath test at least 4 weeks after finishing treatment. RESULTS: Follow up urea breath test was obtained in 120 patients (92%). The eradication rate for separate bottles was 79% and for the medication pack 76%. Compliance was estimated to be greater than 90% in 92% of patients who attended for followup. H pylori culture and sensitivity results were available for 41 patients. Overall rate of metronidazole resistance was 32%. The eradication rate for metronidazole sensitive strains was 89% and for resistant strains 46%. Mild side effects were reported in 10% and moderate side effects in 10%. No patient stopped treatment because of side effects. There was no effect of age, ethnicity, smoking, alcohol intake, pretreatment with H2-antagonists or endoscopic diagnoses on eradication rates. CONCLUSION: The low dose triple therapy has an acceptable real eradication rate. The most important determinant of success was metronidazole resistance. The eradication rate was not improved by using medication packs.

Adult↗

PubMed1996

Diagnostic tests for Helicobacter pylori--can they help select patients for endoscopy?

AIM: Dyspepsia is a common symptom and some selection process for endoscopy is required. This study seeks to determine if noninvasive tests for Helicobacter pylori could be useful as a screening test to help select patients for endoscopy. METHODS: Consecutive patients attending for upper gastrointestinal endoscopy were interviewed prior to endoscopy and the endoscopic diagnoses was recorded. The presence of Helicobacter pylori infection was assessed by serology. Some patients also had a 13C urea breath test or rapid urease test (CLO test). RESULTS: 436 consecutive patients were evaluated. The endoscopy findings were normal in 44%, 29% had reflux oesophagitis, 18% had duodenal ulcer, duodenitis or gastric ulcer and 9% had other diagnoses. 54.8% of patients were positive for Helicobacter serology. Using either the CLO test or 13C urea breath test as the confirmatory test for the diagnosis of Helicobacter pylori, the sensitivity of the serology test was 96% and 91% respectively and the specificity was 66.6 and 82%. Patients with negative serology and no history of recent NSAID or aspirin use comprised 34% of the total with dyspepsia or reflux symptoms. There were no gastric or duodenal ulcers in this group. CONCLUSION: The serology test may have some potential or the initial evaluation of dyspepsia. These tests need to be prospectively evaluated in general practice.

Adolescent↗

PubMed1996

Spontaneous coronary artery rupture and cardiac tamponade in Ehlers-Danlos syndrome type IV.

Spontaneous coronary artery rupture resulted in cardiac tamponade in a man with Ehlers-Danlos syndrome (type IV) presenting with acute onset of cardiac chest pain. Electrocardiograms suggested acute myocardial infarction. The haemopericardium was drained and angiography showed a ruptured distal branch of the left circumflex coronary artery. The patient remains well.

Adult↗

PubMed1996

Follow-up of chronic thoracic aortic dissection: comparison of transesophageal echocardiography and magnetic resonance imaging.

Because survivors of thoracic aortic dissection require follow-up to detect prognostic factors such as intimal tears, persistent flow in the false lumen, and complications associated with grafts, we compared transesophageal echocardiography (TEE) with magnetic resonance imaging (MRI) prospectively in 14 patients 1 year after their initial examination. Residual dissection was identified by both techniques in 11 patients. Flow and/or thrombus in the false lumen were detected by TEE in 10 (91 %) and 6 (55%) patients, respectively, and by MRI in 9 (82%) and 5 (45%), respectively (p = NS); more tears were detected by TEE (2.5 +/- 1.4 per patient vs 0.2 +/- 0.4; p < 0.005). Satisfactory delineation of a graft in the ascending aorta was noted in all 8 (100%) of the surgically treated patients by TEE compared with 4 (50%) by MRI (p < 0.005). The upper ascending aorta was visualized clearly in fewer patients by TEE than by MRI (7 [50%] vs 13 [93%]; p < 0.05), as were the origins of the head and neck vessels (10 [71%] vs 13 [93%], p = NS). We conclude that TEE and MRI are both suitable techniques for the follow-up of patients with aortic dissection. TEE is more sensitive in identifying prognostic factors. MRI has a complementary role, particularly in visualization of the upper ascending aorta and the head and neck vessels.

Adult↗