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Biomedical subjects

G M Forbes

Publications and source records attributed to G M Forbes.

At least 19 recordsLinked to original sources

Detection of Helicobacter pylori antigen in faeces by enzyme immunoassay.

The detection of Helicobacter pylori antigen directly in faecal specimens may offer an alternative non-invasive method for determining the presence of H. pylori infection. This study compared the performance of the Premier Platinum HpSA enzyme immunoassay (HpSA) with histology and CLOtest, a rapid urease test. Of 134 patients undergoing upper gastrointestinal endoscopy, 37 (28%) were H. pylori-positive by histology and CLOtest. Using the HpSA test, H. pylori was detected in 35 H. pylori-positive patients (95% sensitivity) and one H. pylori-negative patient (99% specificity). The positive and negative predictive values for HpSA were 97 and 98%, respectively. HpSA is a rapid, easily performed, non-invasive method for detecting H. pylori.

Antigens, Bacterial↗

Extracolonic findings at virtual colonoscopy: implications for screening programs.

OBJECTIVE: Virtual colonoscopy (VC) is an evolving technology proposed as a possible screening tool for colorectal cancer. In contrast to conventional colonoscopy, VC may detect extracolonic abdominal pathology. This may lead to unnecessary investigation of benign lesions, or may benefit the patient by identifying serious pathology at an early stage. The aim of this study was to assess the prevalence and characteristics of extracolonic pathology found in patients undergoing VC. METHODS: A total of 100 patients aged > or = 55 yr, referred for colonoscopy for bowel symptoms or family history of bowel cancer, underwent VC. Axial views of the abdomen were reviewed prospectively by a single radiologist for extracolonic pathology. Patients with extracolonic abnormalities were referred to their local doctor or to a specialist clinic when appropriate. Case records were reviewed and treating doctors contacted to document subsequent investigations and procedures generated. RESULTS: Fifteen patients (15%) had extracolonic abnormalities detected. In four patients, the pathology had been diagnosed previously (umbilical hernia, gallbladder and renal calculi, 3.5-cm aortic aneurysm, ovarian cyst). Eleven patients had new abnormalities detected: ovarian cysts (three), liver cysts (two), uterine fibroids (two), gallstones (one), splenic calcifications (one), aortic aneurysm (one), and renal tumor (one). Two patients with ovarian cysts underwent surgery, and histology showed benign cysts. CONCLUSIONS: Extracolonic abnormalities are common at VC. Most are benign, but may lead to investigative and procedural costs. These data should be carefully evaluated in feasibility and cost-effectiveness studies on colorectal cancer screening using VC.

Aged↗

Computed tomography colonography.

Computed tomography colonography (virtual colonoscopy) is an exciting technique that continues to evolve but promises to be a valuable tool for diagnosis of and screening for colorectal neoplasia.

Colonography, Computed Tomographic↗

Proteome analysis of Helicobacter pylori: major proteins of type strain NCTC 11637.

Proteome analysis involves the simultaneous resolution and display of proteins produced by an organism, followed by the quantitation, characterisation and identification of these proteins. As part of an ongoing study mapping and comparing the proteins expressed by various strains of the pathogenic bacterium Helicobacter pylori, we have resolved and identified 93 of the most abundant proteins expressed by type reference strain NCTC 11637. Proteins were separated by two-dimensional gel electrophoresis and stained with Coomassie G250. Intensely-stained spots were excised and digested with trypsin, and the resulting peptides were characterised by mass spectrometry. Proteins were then identified by correlating actual peptide profiles with theoretical profiles generated from published nucleotide sequences. Ninety-three of the most intensely-stained protein spots were identified as the products of 35 genes, giving a ratio of 2.7 protein gene-products per gene. The products of the tsaA, pfr, ureA and ureB genes were amongst several proteins present in multiple isoforms. Peptide mass fingerprinting data were used to identify probable post-translational protein modifications. These results suggest that H. pylori proteins are subject to a high degree of post-translational modification. Comparative proteomics of H. pylori strains should greatly assist in investigating the pathogenic properties of this bacterium.

Bacterial Proteins↗

Virtual colonoscopy compared with conventional colonoscopy: a developing technology.

AIM: To determine the accuracy of computed tomography colography (virtual colonoscopy) in detecting colorectal polyps and colorectal cancer. DESIGN: Blinded comparison of virtual colonoscopy (initially supine-only scans and later supine plus prone scans) with the criterion standard of conventional colonoscopy. SUBJECTS AND SETTING: 100 patients aged 55 years or over referred to a public teaching hospital for colonoscopy, July 1997 to January 2000, because of colonic symptoms or a family history of bowel cancer. MAIN OUTCOME MEASURES: Presence and size of polyps and other lesions; certainty of polyp identification on virtual colonoscopy (on 100-point visual analogue scale); sensitivity and predictive values of virtual colonoscopy. RESULTS: Conventional colonoscopy identifed 121 polyps in 47 patients; 28 of these polyps, in 19 patients, were identified by virtual colonoscopy. Sensitivity of virtual colonoscopy for detecting polyps (using supine plus prone scans) was 73% for polyps with diameter > or = 10 mm (95% CI, 39%-94%) and 19% for smaller polyps (95% CI, 10%-31%) (P < 0.001); corresponding figures for supine-only scans were 57% (95% CI, 18%-90%) and 11% (95% CI, 4%-24%), respectively. Ten polyps identified at virtual colonoscopy were considered false-positive findings (8%). The value of finding a polyp on virtual colonoscopy (with thresholds of 5 mm for diameter and 30 points for certainty score) was assessed as a predictor of finding a polyp (diameter > 5 mm) on conventional colonoscopy. Positive and negative predictive values were 88% and 89%, respectively, for supine plus prone scans. CONCLUSION: Although virtual colonoscopy shows potential as a diagnostic tool for colorectal neoplasia, it is currently not sufficiently sensitive for widespread use.

Colon↗

Nitrous oxide for colonoscopy: a randomized controlled study.

BACKGROUND: Intravenous sedation/analgesia for colonoscopy is accompanied with certain risks and postprocedure drowsiness. We sought to determine whether inhaled nitrous oxide (Entonox: 50% nitrous oxide, 50% oxygen) provides adequate analgesia for colonoscopy and the impact of this agent on recovery. METHODS: All patients undergoing outpatient colonoscopy were considered for the study (n = 248) except those with previous colonic resection. Data for patients unsuitable for randomization (n = 58) and those who declined to participate (n = 88) were also analyzed. RESULTS: One hundred two patients were randomized to receive inhaled Entonox alone (n = 56) or intravenous midazolam and meperidine (n = 46). Forty-nine (88%) patients randomized to Entonox underwent complete colonoscopy without conversion to intravenous medications. Entonox patients reported more pain (p < 0.0001), tolerated colonoscopy less well (p < 0.0001), were less satisfied (p = 0.01), and less willing to undergo colonoscopy again under the same circumstances (p = 0.04). Of patients receiving intravenous medication, 91% found colonoscopy less unpleasant and 9% as unpleasant as anticipated; this compares with 52% and 21% Entonox patients, respectively, and an additional 27% Entonox patients who found colonoscopy more unpleasant than anticipated. Recovery was faster among Entonox patients (median 30 versus 60 minutes, p < 0.0001). CONCLUSION: Entonox is less effective than midazolam with meperidine for colonoscopy but is acceptable in many patients and allows faster recovery.

Administration, Inhalation↗

Clinical relapse in Whipple's disease despite maintenance therapy.

Whipple's disease is a multisystem disorder that was first reported just over 100 years ago. Only recently, the bacillus responsible for the condition was identified and subsequently cultured. However, differences of opinion remain regarding the best antibiotic regimen and duration of therapy at primary diagnosis and there is also great uncertainty about the management of disease relapse. We report a case of clinical relapse of Whipple's disease in a man who was on a prolonged therapy with trimethoprim-sulfamethoxazole. We describe his management and review the literature on the treatment of this condition, with particular reference to the recurrence of the disease.

Administration, Oral↗

Treatment of Helicobacter pylori infection to reduce gastric cancer incidence: uncertain benefits of a community based programme in Australia.

Helicobacter pylori is a cause of gastric adenocarcinoma, but the role of H. pylori eradication in reducing cancer risk is unknown. We sought to estimate the benefits of a screening and treatment programme for H. pylori infection, aimed at reducing the incidence of gastric cancer in Australia. The impact of this programme on cancer incidence was evaluated in sensitivity analyses utilizing Western Australian Cancer Registry data and published data on the epidemiology of H. pylori and gastric cancer. The impact of variation in parameters used in the sensitivity analyses was substantial, ranging from a 38% reduction in lifetime risk of gastric cancer in a best-case to 3% in a worst-case scenario. In an intermediate-case scenario there is a 23% reduction in lifetime risk, but in real terms this reflects a fall in cumulative incidence from 0.7 to 0.5% for males or 0.3 to 0.2% for females. The projected cumulative lifetime incidence of gastric cancer in H. pylori-infected males is 2.2% and 0.9% for females; this contrasts with 0.4 and 0.2%, respectively, for those never infected. According to an intermediate-case scenario, to prevent one gastric cancer, screening with or without subsequent treatment would be required in 617 men or 1639 women. Furthermore, this programme may be less effective in reducing cancer incidence than would be achieved naturally over the next 15 years, providing the current annual decline in gastric cancer incidence continues. In conclusion, the benefits of a community based programme of H. pylori eradication in terms of cancer risk reduction remain unclear, related largely to uncertainties in the parameters used to calculate these benefits. In Australia, any benefits obtained are likely to be, at best, modest.

Australia↗

Short duration therapy for Helicobacter pylori in Western Australia: the impact of metronidazole resistance.

BACKGROUND: Limited Australian data are available on either short duration therapy for Helicobacter pylori infection, or the impact of metronidazole resistance on the outcome of treatment. AIM: To compare the efficacy of two treatment regimens and determine the influence metronidazole resistance has on clearing H. pylori infection. METHODS: Eighty patients with H. pylori infection proven at upper gastrointestinal endoscopy, none of whom had previously received therapy for H. pylori, were randomised to one week therapy with either bismuth subcitrate one tablet qid, tetracycline 500 mg qid and metronidazole 400 mg tds (BTM), or lansoprazole 30 mg bd, amoxycillin 500 mg qid and metronidazole 400 mg tds (LAM). Effectiveness of therapy was measured by C14-urea breath test at six weeks. RESULTS: On an intention-to-treat basis, clearance of infection was achieved in 17 of 32 (53%; 95% CI: 35-71%) evaluable patients receiving BTM and 32 of 46 (70%, 54-82%) patients receiving LAM (p = 0.16). Metronidazole resistance was found in 32 of 65 (49%) patients in whom H. pylori was isolated by culture. On a per-protocol basis, of patients who had metronidazole sensitive strains of H. pylori 23 of 24 (96%) cleared infection after therapy with either BTM or LAM, compared with 14 of 24 (58%) who were metronidazole resistant (p = 0.004). Clarithromycin resistance was not found in 45 patients tested. CONCLUSIONS: In Western Australia clearance rates of H. pylori infection, after one week of BTM or LAM, are lower than in other published series. The high incidence of metronidazole resistance is the main determinant of our relatively poor eradication rates.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Review: Helicobacter pylori. Current issues and new directions.

The present review outlines current management issues and controversies related to Helicobacter pylori infection. Clearance of this infection markedly reduces the likelihood of duodenal and gastric ulcer recurrence and may result in the regression of low grade primary gastric lymphoma. Recent therapeutic advances have seen the development of simpler drug regimens to treat H. pylori that have fewer side effects and are shorter in duration. Clearance of the infection can be achieved in 80-95% of patients treated, depending on the drug regimen used, compliance with medications and antibiotic sensitivity. In developed nations reinfection is uncommon after successful treatment. Data do not currently support treatment of this infection for non-ulcer dyspepsia or for the prevention of gastric cancer, although whether certain individuals or populations may benefit from such treatment remains to be clarified.

Anti-Bacterial Agents↗

Ultrastructural evidence of intestinal mucosal macrophage activation after bone marrow transplantation.

Previous studies have demonstrated upregulation of intestinal mucosal macrophage CD16 (an Fc receptor for IgG) in bone marrow transplant (BMT) recipients with graft-versus-host disease (GVHD). We sought to determine whether there was ultrastructural evidence of mucosal macrophage activation in allogeneic BMT recipients and relate appearances to those seen in autologous BMT patients and to immunohistological findings. Sigmoid colonic mucosal biopsies from five allogeneic and three autologous BMT patients were taken prior to, 30 days after transplant and, in three of the allogeneic patients, 120 days after transplant. These were examined by immunohistochemistry and electron microscopy. Immunohistological analysis revealed upregulation of lamina propria macrophage CD16 after transplant in all patients except one autologous BMT recipient; there were no such changes in total macrophage numbers. Ultrastructural evidence of lamina propria macrophage activation was prominent after both allogeneic and autologous BMT. There was an increase in nuclear size accompanied by increased euchromatin and larger nucleoli. In the cytoplasm there were increased numbers of lysosomes, many of which were small and cylindrical, and cytoplasmic flaps were prominent. Phagosomes were less numerous after transplant. These data confirm that after BMT intestinal mucosal macrophages become activated. However changes in macrophage ultrastructure specific to patients at risk of developing clinical GVHD are lacking.

Adult↗

Long-term follow-up of gastric histology after Helicobacter pylori eradication.

Helicobacter pylori causes chronic active gastritis and is thought to be associated with the development of gastric atrophy, intestinal metaplasia and carcinoma. As the effect of H. pylori eradication on this process is poorly understood, we sought to determine the long-term effects of H. pylori eradication on gastric histology. Fifty-four patients with duodenal ulceration associated with H. pylori infection received H. pylori eradication therapy in 1985/86 and either remained infected (n = 22) or had the infection eradicated (n = 32); patients were followed up by endoscopy with gastric antral biopsy for 7.1 years (mean). Histopathological analysis of gastric antral mucosa from patients rendered H. pylori-negative revealed a marked decrease in both inflammatory cells within the lamina propria and intraepithelial neutrophils and an increase in epithelial mucinogenesis. Gland atrophy remained unchanged in both H. pylori-positive and -negative patients. When examined for the presence and severity of intestinal metaplasia, there was neither a difference between the two patient groups nor a change with time. These data demonstrate that significant long-term improvements in gastric histology accompany H. pylori eradication when compared with histology in patients with persistent infection. Whether this confers a protective effect by reducing the risk of gastric carcinoma remains unknown.

Adult↗