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Biomedical subjects

S Saverymuttu

Publications and source records attributed to S Saverymuttu.

12 recordsLinked to original sources

Molecular epidemiology of Helicobacter pylori in England: prevalence of cag pathogenicity island markers and IS605 presence in relation to patient age and severity of gastric disease.

The cagA gene is a key marker for the Helicobacter pylori cag pathogenicity island (PAI), which may vary in composition in different strains with insertion sequence mediated interruptions and deletions of genes. While presence of cagA has been associated with increased risk for peptic ulcer disease and gastric cancer, the precise link with virulence is controversial. We investigated H. pylori from dyspeptics in one location in England (mid-Essex) with reference to the prevalence and distribution by age cohort of different cag PAI forms to determine if presence of the insertion element IS605 had a modifying effect on the severity of associated disease. H. pylori isolated from gastric biopsies over a 4-year period were screened by specific PCR assays for the presence of cagA, cagD, cagE and virD4 genes in the cag PAI, and for the presence of IS605 in the PAI and elsewhere in the genome. Most (68%) of the 166 isolates of H. pylori contained a PAI based on detection of cagA whereas 29% had no detectable PAI using multiple loci. The cagA+ genotype frequencies were similar in the peptic ulcer and non-ulcer dyspepsia-gastritis groups (79% vs. 74%) whereas frequencies in the NUD-oesophagitis and normal mucosa groups were lower (58%) but not significantly different (P>0.41). Genomic IS605 inserts were present at an overall frequency of 32% and were widely distributed with respect to patient age and disease severity. The combined cagA+/IS- strain genotype was common but not significantly associated with PUD compared to endoscopically normal mucosa (P> or =0.807). We concluded that presence of the IS605 element, whether in cagA+ or cagA- strains of H. pylori, did not systematically modify the severity of associated disease in the study population.

Adolescent↗

PCR-based diagnosis of Helicobacter pylori infection and real-time determination of clarithromycin resistance directly from human gastric biopsy samples.

A novel PCR detection assay that amplifies the Helicobacter pylori-specific vacuolating cytotoxin gene (vacA) and thus enables rapid diagnosis of infection is described. Additionally, a real-time probe hybridization melting point analysis assay to detect all three mutations in the 23S rRNA gene associated with clarithromycin resistance was applied directly to antral gastric biopsy samples. Comparison with culture and an alternative PCR assay targeting the 16S rrn gene showed that the vacA assay was sensitive and specific when tested on biopsy samples from 121 patients. Clarithromycin susceptibilities could be determined in the majority (92.3%) of culture-positive gastric biopsy samples analyzed, four of which generated melting peaks indicative of clarithromycin resistance by either an A-->G or A-->C mutation. The presence of the mutations correlated with the clarithromycin disk diffusion sensitivities of matched cultures. This PCR-based system was simple to perform and could be completed in 3 to 4 h, thereby overcoming the delays associated with conventional culture methods for H. pylori identification and susceptibility testing.

Anti-Bacterial Agents↗

Genetic diversity in the Helicobacter pylori cag pathogenicity island and effect on expression of anti-CagA serum antibody in UK patients with dyspepsia.

AIMS: To investigate variation within the cag pathogenicity island (PAI) of Helicobacter pylori isolated from patients with dyspepsia in mid-Essex, and to evaluate the effect on expression of anti-CagA antibody. METHODS: Sixty two isolates of H pylori cultured from gastric biopsies were screened by specific PCR assays for the presence of cagA and other gene markers (cagD and cagE, and virD4) in the cag PAI. An enzyme linked immunosorbent assay (ELISA) kit (Viva Diagnostica helicobacter p120) was used to test for anti-CagA IgG antibody in matching sera. Isolates were also genotyped by vacuolating cytotoxin polymerase chain reaction (PCR) analysis, and tested for absence of the complete cag PAI (empty site PCR assay). RESULTS: Forty one of the H pylori isolates had a cag PAI containing cagA. One strain had no cagA but other cag PAI loci were present, whereas the remaining 20 strains had no detectable cag PAI markers. Anti-CagA IgG antibody was detected in 34 sera by the ELISA assay, and when compared with the cag PAI genotype of the infecting strain, accuracy, sensitivity, and specificity were 92%, 87%, and 100%, respectively. The seven discrepant or borderline strains in the ELISA were all vacA s1 but differed in other genotypic markers. CONCLUSIONS: The cag PAI was widely distributed in H pylori from patients with dyspepsia in mid-Essex who had different gastric pathologies. Infection with a strain having an uninterrupted cag PAI was associated with the presence of anti-CagA antibody in most patients. Discrepant ELISA results, mostly for elderly patients with duodenal ulcers, were attributed to cagA associated variation, particularly to the presence of mixed cagA+/cagA- cell variants in the infecting strain population. Tests for anti-CagA serum antibody were unreliable for predicting severity of clinical disease associated with H pylori infection in this series of patients.

Adult↗

Ultrasound in the diagnosis of granulomatous liver disease.

Ultrasound is a widely used method of assessing the liver for space occupying lesions and, more recently, parenchymal liver disease. We have reviewed the ultrasound scans and reports of 11 patients with biopsy proven granulomatous liver disease. Multiple echogenic lesions 3-5 mm in diameter, each surrounded by an hypoechoic halo, were seen in the liver of all the patients and in the spleens of three patients. A specific diagnosis of granulomatous hepatitis was suggested at the time of scanning in seven patients. An abnormal liver was noted in the other four patients but no specific diagnosis was suggested. We believe that granulomata in the liver can be detected using ultrasound and, if the above appearances are seen during an ultrasound scan, a diagnosis of granulomatous hepatitis should be considered.

Adult↗

Controlled trial comparing prednisolone with an elemental diet plus non-absorbable antibiotics in active Crohn's disease.

In a randomised clinical trial, patients with moderately active Crohn's disease received either prednisolone 0.5 mg/kg/day plus a normal diet, or an elemental diet plus oral framycetin, colistin and nystatin. Patients were assessed using the Crohn's disease activity index (CDAI), ESR, and faecal granulocyte excretion quantified by 111In-autologous leucocytes. Five patients were intolerant of the elemental diet plus antibiotics and were withdrawn from the trial within 72 hours. Sixteen patients completed 10 days treatment on each regime. Fifteen of 16 patients on elemental diet plus antibiotics and all 16 patients on prednisolone improved with marked, but statistically indistinguishable falls in CDAI, ESR, and faecal granulocyte excretion between the two groups. Thus a regime decreasing the intraluminal concentration of bacteria and complex food molecules, was associated with rapid improvement in activity of Crohn's disease. This suggests that these intraluminal factors play a role in maintaining inflammation and that their removal or alteration offers an approach to management.

Adult↗

Coeliac disease, adenocarcinoma of jejunum and in situ squamous carcinoma of oesophagus.

The development of both adenocarcinoma of the jejunum and in situ squamous carcinoma of the oesophagus in an adult coeliac patient is described. Good evidence that adenocarcinoma of jejunum occurs more frequently in patients with coeliac disease has recently become available though this association has been suggested for some time. While oesophageal carcinoma has long been associated with coeliac disease, in situ carcinoma of oesophagus has not been previously described in these circumstances. We feel that the risk of this complication, as calculated from published series, warrants a screening programme for oesophageal malignancy in adult coeliacs.

Adenocarcinoma↗

A variant alkaline phosphatase in renal cell carcinoma.

We report a case of renal cell carcinoma in which up to 32% of the abnormally increased alkaline phosphatase activity in serum was contributed by a variant alkaline phosphatase originating in the primary tumor and its secondary deposits. The variant enzyme was probably an altered form of normal renal alkaline phosphatase. The rest of the alkaline phosphatase activity in the serum was of hepatic origin, but no abnormality of the liver was discovered at autopsy.

Adenocarcinoma↗

A method for assessing responses of small arteries in man: effect of physiological and pharmacological stimuli.

1. A method has been developed for estimating resistance to blood flow in the collateral arteries around the elbow. Arterial pressure is recorded continuously from the radial artery and blood flow in the forearm and hand is measured by venous occlusion plethysmography. The brachial artery is occluded for short periods, and the pressure drop across the collaterals and the flow through them are determined. From these observations an index of resistance can be calculated. 2. During 2 min occlusions of the brachial artery, collateral arterial resistance fell progressively to reach a level that was on average 45% lower than the initial resistance (P less than 0.01). 3. There was an inverse relation between distending pressure in the collateral arteries and calculated resistance. 4. Ergotamine tartrate (0.25 mg intravenously) increased collateral resistance by an average of 135%. Glyceryl trinitrate (0.5 mg sublingually) reduced collateral resistance by an average of 45%. Hydrallazine and isoprenaline had an inconsistent dilator effect; the direct action of these drugs may have been offset by the reduction in distending pressure which they induced. 5. The elbow collateral arteries provide a useful model for studying physiological and pharmacological responses of small limb arteries in man.

Adult↗