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Biomedical subjects

P Patel

Publications and source records attributed to P Patel.

At least 127 records · Page 7Linked to original sources

Pathogenesis of gastric metaplasia of the human duodenum: role of Helicobacter pylori, gastric acid, and ulceration.

BACKGROUND & AIMS: The pathogenesis of gastric metaplasia (GM) in the duodenum is unclear. The aim of this investigation was to study the effect on the extent of GM of ulcer healing, Helicobacter pylori eradication, and acid suppression singly and in combination. The relationship between GM and gastroduodenal inflammation and H. pylori infection density was also studied. METHODS: Duodenal and gastric antral biopsy specimens were obtained from H. pylori-positive patients with duodenal ulcer and from H. pylori-positive nonulcer subjects. Biopsy procedures from patients with duodenal ulcer were repeated after 6 months of treatment. Nonulcer subjects were treated symptomatically and did not undergo re-endoscopy. RESULTS: Ulcer healing alone produced no change in GM or in gastroduodenal inflammation. H. pylori eradication produced a 42% reduction in GM and improvement in inflammation. Acid suppression produced a 43% reduction in GM but without a significant change in inflammation. A combination of H. pylori eradication and acid suppression produced an additive effect with a 66% reduction in GM. A positive relationship was detected between the extent of GM and antral H. pylori density, duodenitis score, and antral gastritis score. CONCLUSIONS: This study shows that the extent of duodenal GM is unrelated to the presence or absence of ulceration but is partly due to H. pylori and partly due to acid.

Adult↗

The magnetic immuno-polymerase chain reaction assay for the detection of Campylobacter in milk and poultry.

A rapid and sensitive technique, based on the magnetic immuno-polymerase chain reaction assay (MIPA), was developed for the detection of Campylobacter jejuni in milk and chicken products. Target bacteria are captured from the food sample by magnetic particles coated with a specific antibody and the bound bacteria then lysed and subjected to PCR. The MIPA could detect 420 cfu g-1 of chicken after 18 h, 42 cfu g-1 after 24 h, and 4.2 cfu g-1 after 36 h enrichment. For artificially contaminated milk 63 cfu ml-1 could be detected after 18 and 24 h and 6.3 cfu ml-1 after 36 h enrichment.

Animals↗

Radiosurgical management of meningiomas.

The management of residual, recurrent, or small skull base meningiomas is controversial. Stereotactic radiosurgery has emerged as an alternative treatment. We report our experience from September 1991 to August 1994 of treatment of 20 such patients [18 females -age 19-82 years, followed for 6-36 months (mean 15.5 months)] with the Leksell Gamma Knife. Nine patients were treated either with recurrent (2 patients-2 operations each) or residual tumor. Twelve patients had skull base, 3 optic nerve, 3 parasagittal, and 1 residual torcular tumor. Mean volume/diameter was 9.172 mm3/25 mm.

Adult↗

Medical student suicide, 1989-1994.

OBJECTIVE: Studies examining suicide rates for medical students have yielded conflicting data. This article addresses medical student suicide from August 1989 through May 1994. METHOD: Telephone interviews were conducted with a representative from each U.S. medical school, generally the dean of student affairs. If a suicide had occurred, information regarding demographic characteristics, psychiatric or substance abuse history, means of suicide, month, and presence of a suicide note was obtained. RESULTS: Responses were obtained from 101 (80%) of the 126 U.S. medical schools. Responding schools reported 15 suicides by medical students from August 1989 through May 1994. Fourteen were by men. Six suicides were committed during the third year of medical school, and four occurred during the fourth year. Six students left notes, and nine of 13 had psychiatric histories. CONCLUSIONS: The results demonstrate a lower suicide rate than that found in previous studies and emphasize the need for standardized reporting methods.

Adolescent↗

Decreased thrombin activity of fibrin clots prepared in cord plasma compared with adult plasma.

We hypothesized that the immaturity of the newborn coagulation system may influence the procoagulant activity of clotbound thrombin. 125I-Labeled fibrin clots were prepared from adult and cord plasma, incubated in their respective plasmas, and fibrinopeptide A (FPA) production was measured. Cord plasma clots generated significantly less FPA compared with adult plasma clots (p < 0.001). Cord plasma clots incubated in adult plasma generated similar amounts of FPA as cord plasma clots in cord plasma. Adult plasma clots incubated in cord plasma clots generated more FPA than adult plasma clots in adult plasma. Adult and cord plasma clots were then incubated with purified human adult fibrinogen, and the discrepancy between adult and newborn plasma clots remained (p < 0.01). To compare the amount of clot bound thrombin, adult and cord plasma clots were sonicated and incubated with fibrinogen. Again, significantly less thrombin was seen in cord clots compared with adult clots (p < 0.01). Because cord plasma has lower prothrombin concentrations (0.5 U/mL) we increased cord plasma prothrombin concentration by the addition of purified prothrombin. Prothrombin supplemented cord plasma clots generated more thrombin than unsupplemented clots (p < 0.01) and in amounts similar to the adult system. In conclusion, decreased amounts of thrombin present in cord plasma clots compared with adult plasma clots results in less FPA production. The low plasma concentration of prothrombin in cord plasma is responsible for this phenomenon.

Adult↗

Synthesis of some novel pyrazoline and cyanopyridine derivatives as antimicrobial agents.

Substituted chalcones 2a-j prepared by the treatment of 4'(p-chlorophenylsulphonamido)acetophenone 1 with araldehydes, on condensation with hydrazine hydrate in ethanol and acetic acid provided the desired pyrazolines of the type 3a-j and 4a-j. The same chalcones 2a-j made to react with malononitrile in the presence of ammonium acetate yielded cyanopyridines 5a-j. The structure was confirmed by elemental analyses, IR, NMR and MS spectral studies. The pharmacological profile of the compounds synthesised is described. Most of the compounds displayed their maximum activity against E. coli. Compounds 2b, 2d, 5b, 5d, 5e, 5h and 5i have been selected for their agrochemical screening by DuPont Agricultural Products, U.S.A.

Anti-Bacterial Agents↗

Prospective screening of dyspeptic patients by Helicobacter pylori serology.

Helicobacter pylori infection is associated with 95% of duodenal ulcers and more than 80% of gastric ulcers. Several reports have indicated that screening for H pylori may avoid subsequent endoscopic examination. We screened 183 dyspeptic patients, aged under 45, by taking a history of sinister symptoms and regular use of non-steroidal anti-inflammatory drugs (NSAIDs), together with serological testing for H pylori. Endoscopy was performed on 113 patients, of whom 90 (49%) were seropositive, 14 (8%) had sinister symptoms, and 9 (5%) had used NSAIDs regularly. In 34 (19%) patients we detected peptic ulceration. The remaining 70 (38%) patients who were H pylori seronegative, had no sinister symptoms, and had not taken NSAIDs (screen-negative), did not undergo endoscopy but were returned to their primary care physician for treatment of symptoms. At subsequent reassessment (of the non-endoscoped group), symptom severity (p = 0.002), interference with life events (p = 0.01), and medication (p = 0.0002) were all significantly lower in the 6 months after screening than in the 6 month period before screening. Only three screen-negative patients were re-referred after screening but their endoscopic findings were normal. Thus, 67 (36%) endoscopies were avoided. When the non-endoscoped screen-negative patients were compared with a cohort of endoscoped screen-negative patients, the groups did not differ in terms of symptom severity (odds ratio 1.12, 95% CI 0.53-2.35, p = 0.77) or interference with life events (0.82, 0.38-1.76, p-0.61). However, medication use was significantly less (0.37, 0.17-0.80, p = 0.01) in those who did not have an endoscopy. Our study indicates that colonisation screening based on H pylori serology, a history of sinister symptoms, or a history of NSAID use was worthwhile in dyspeptic patients. We avoided 37% of endoscopies and reduced drug usage without disadvantaging those not endoscoped.

Adult↗

Association of Helicobacter pylori and Chlamydia pneumoniae infections with coronary heart disease and cardiovascular risk factors.

OBJECTIVE: To investigate the relation between seropositivity to chronic infections with Helicobacter pylori and Chlamydia pneumoniae and both coronary heart disease and cardiovascular risk factors. DESIGN: Cross sectional study of a population based random sample of men. Coronary heart disease was assessed by electrocardiography, Rose angina questionnaire, and a history of myocardial infarction; serum antibody levels to H pylori and C pneumoniae were measured, risk factor levels determined, and a questionnaire administered. SETTING: General practices in Merton, Sutton, and Wandsworth, south London. SUBJECTS: 388 white south London men aged 50-69. MAIN OUTCOME MEASURES: Evidence of coronary risk factors and infection with H pylori or C pneumoniae. RESULTS: 47 men (12.1%) had electrocardiographic evidence of ischaemia or infarction. 36 (76.6%) and 18 (38.3%) were seropositive for H pylori and C pneumoniae, respectively, compared with 155 (45.5%) and 62 (18.2%) men with normal electrocardiograms. Odds ratios for abnormal electrocardiograms were 3.82 (95% confidence interval 1.60 to 9.10) and 3.06 (1.33 to 7.01) in men seropositive for H pylori and C pneumoniae, respectively, after adjustment for a range of socioeconomic indicators and risk factors for coronary heart disease. Cardiovascular risk factors that were independently associated with seropositivity to H pylori included fibrinogen concentration and total leucocyte count. Seropositivity to C pneumoniae was independently associated with raised fibrinogen and malondialdehyde concentrations. CONCLUSIONS: Both H pylori and C pneumoniae infectins are associated with coronary heart disease. These relations are not explained by a wide range of confounding factors. Possible mechanisms include an increase in risk factor levels due to a low grade chronic inflammatory response.

Aged↗

The receptor tyrosine kinase-related gene (ryk) demonstrates lineage and stage-specific expression in hematopoietic cells.

We attempted to isolate novel receptor tyrosine kinase, which may play a role in hematopoietic development by screening for expressed sequences with conserved tyrosine kinase catalytic domains. Among the known tyrosine kinases identified in this screen, we found a gene with characteristics of a receptor tyrosine kinase but unusual motifs in the catalytic domain. This gene is identical to ryk described independently by other investigators. Chromosomal fluorescence in situ hybridization localization of human ryk was clarified by using monochromosomal hybrids and placing it as a single locus in 3q22. Although Northern analysis reveals widespread expression in adult mouse tissues, we have found that ryk expression is not ubiquitous. Expression increased in bone marrow cells from mice treated with 5-fluorouracil. Northern analysis on cell lines indicates expression in CD3-, CD4-, CD8- T cells (at a low level), pre-T cells, thymic epithelial cells, and mature myeloid cells, but not myeloid precursors or B cell precursors. Expression analysis with the use of RT-PCR on mouse bone marrow cells separated on the basis of cell surface markers (B220, CD4, CD8, Gr-1, Mac-1) reveals that this receptor is expressed in differentiated cells (Lin+) but is not expressed in the precursor cells (Lin-). Flow cytometric analysis with a monospecific anti-Ryk Ab demonstrates that Ryk+ cells constitute 36.7% and Lin+/Ryk+ cells constitute 33.7% of low density bone marrow cells whereas Ryk+ cells represent only 0.3% of the Lin- population. We conclude that ryk expression is regulated during hematopoietic development by lineage commitment and stage of maturation.

Amino Acid Sequence↗

Chlamydia pneumoniae: risk factors for seropositivity and association with coronary heart disease.

BACKGROUND: Two studies have suggested that seropositivity for Chlamydia pneumoniae (C. pneumoniae) is a risk factor for coronary heart disease (CHD) but the association remains tenuous. Further data is required in other populations to consolidate this observation. AIMS: Initially to determine descriptive risk factors for C. pneumoniae seropositivity in a general population sample and subsequently to examine the relation of seropositivity for this organism to CHD for the first time in a British population. SETTING: A single general practice health screening clinic and a cardiology clinic involving patients predominantly residing in south London and Surrey. SUBJECTS: 210 consecutive caucasian men (62%) and women (38%) aged 18-79 including 67 men aged 45-65. This latter group acting as controls were then also compared with 103 consecutive males aged 45-65 with angiographically confirmed coronary heart disease. METHODS: A questionnaire was administered by a research nurse and serum was analysed for IgG and IgA against C. pneumoniae and other Chlamydiae by a microimmunofluorescence test. Serum was said to be low positive at a specific IgG antibody titre of 16-32, and high positive if 64 or greater. RESULTS: Amongst the general practice health screening clinic population 14 subjects (7%) were excluded due to possible cross-reactivity with other Chlamydia species (predominantly C. trachomatis). Of the remaining 196 subjects, 13 (6%) had high positive C. pneumoniae IgG titres, 68 (35%) had low titres and 125 had no detectable antibody. After adjustment for sex, age, smoking history, social class and family size only one risk factor for high positive titres in this group was identified, which was the number of children currently living in the home (OR 2.29 (1.09-4.80), P = 0.03). No factors were significantly related to low titres. 22/100 (22%) cases with coronary heart disease and 3/64 (4.7%) of controls had high positive IgG titres for C. pneumoniae. Similarly 21% of cases and 9.4% of controls had positive C. pneumoniae specific IgA serology. 45% of cases and 44% of controls had low C. pneumoniae IgG titres. The association of CHD with a C. pneumoniae IgG titre of 64 or above was independent of all risk factors (OR 7.4 (1.7-33.1), P < 0.01). CONCLUSION: Serological evidence of C. pneumoniae infection is common amongst healthy British subjects. Smoking and social class are not important confounding variables in this study. Reinfection from contact with infected children in the home may be important in inducing higher titres in some subjects. These higher titres are more prevalent in subjects with coronary heart disease in the U.K. as reported in Finland and the U.S.A., and provide further evidence that C. pneumoniae may be important in the pathogenesis of this condition in these populations.

Adolescent↗

The effects of unsaturated fatty acids on Helicobacter pylori in vitro.

The effects of three unsaturated free fatty acids on Helicobacter pylori growth in vitro was determined. Growth of H. pylori in Brucella broth was inhibited in a dose-dependent manner by arachidonic, linoleic and oleic acids. The degree of inhibition at any one concentration was related to the degree of fatty acid unsaturation. Triolein, a triacylglycerol ester of oleic acid did not inhibit growth. Inhibition of H. pylori growth was associated with disruption of cell membranes. Incubation with 14C linoleic acid and 14C oleic acid showed incorporation of these fatty acids into H. pylori cell mass and phospholipids leading to alteration of the phospholipid composition of the organism. Incorporation was greater with linoleic than oleic acid and this was associated with a greater inhibition of growth. These findings indicate that H. pylori is sensitive to unsaturated free fatty acids through their incorporation into phospholipids and membrane destruction. This may have therapeutic implications.

Arachidonic Acids↗

Clinical characteristics of subjects with a missense mutation in glucokinase.

The clinical characteristics of subjects with a missense glucokinase mutation, gly299-->arg, were studied in a large pedigree, BX, initially characterized by some members having Maturity Onset Diabetes of the Young (MODY). Glucose tolerance, beta cell function and insulin sensitivity were measured with Homeostasis Model Assessment (HOMA) and with a 'Continuous Infusion of Glucose with Model Assessment' (CIGMA) test. Diabetic complications were clinically assessed. Subjects with glucokinase gly299-->arg were the same age, height, and obesity as the subjects without the mutation. Diabetes was usually asymptomatic at diagnosis and was treated with diet alone in 15 of the 18 subjects. Five of the 11 adult females had been diagnosed when they developed gestational diabetes. The fasting plasma glucose concentrations at the time of study were 4.3-12.6 mmol l-1, with the higher levels being in the more obese (p < 0.05) and in the older subjects (p < 0.05). In subjects with the mutation, beta cell function was impaired, being geometric mean 63% (normal-100%) compared with 126% in the subjects without the mutation (p < 0.001) measured by HOMA and in a subset assessed by CIGMA 59% and 127% (p < 0.01), respectively. There was no difference in fasting insulin concentrations, insulin sensitivity, lipid concentrations or blood pressure between the groups. The haemoglobin A1c was raised (mean 6.5% compared with 5.5% in the subjects without the mutation), but microvascular and macrovascular complications were uncommon. The subjects with the mutation did not have microalbuminuria but had an impaired vibration perception threshold compared with subjects without the mutation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effect of Helicobacter pylori eradication on gastric metaplasia of the duodenum.

Helicobacter pylori associated duodenal ulcers occur in patches of gastric metaplasia. The pathogenesis of gastric metaplasia is unclear, but it has been produced in experimental animals by acute injury and has been shown to be present to a greater extent of H pylori positive subjects. This study aimed to discover if gastric metaplasia regressed with eradication of H pylori or healing of duodenal ulcers, or both. Thirty two duodenal ulcer patients with H pylori infection confirmed by biopsy urease test and by antral histological examination were studied. Patients were treated with triple therapy (deNol 240 mg twice daily, amoxycillin 500 mg three times daily, and metronidazole 400 mg three times daily) for two weeks after the first endoscopy and were subsequently re-endoscoped. Three duodenal bulb biopsy specimens were obtained per patient at each endoscopy. Biopsy sections were stained with haematoxylin and eosin to determine the severity of duodenitis, and with diastase periodic acid-Schiff/alcian blue to assess the extent of gastric metaplasia. Slides were assessed by two histopathologists unaware of treatment status. H pylori was eradicated in 63% of subjects and all ulcers were healed at follow up. The median extent of gastric metaplasia at the start of treatment and 6-18 months (median 10) after treatment was compared in the two groups. Gastric metaplasia declined in eradicators from 16% to 8% (p < 0.05) while in non-eradicators there was no significant change (25% initially and at follow up). A positive relation between extent of gastric metaplasia and duodenal inflammation score was present before treatment (r(s) = 0.74, p < 0.001) and was unchanged after treatment in the non-eradicator group (r(s) = 0.89, p < 0.001). In the eradicator group, however, the inflammation score had significantly declined (p < 0.02) and the close relation with gastric metaplasia was no longer present. These results suggest that H pylori itself is at least in part responsible for producing gastric metaplasia of the duodenum.

Adult↗

Expression of trefoil peptides pS2 and human spasmolytic polypeptide in gastric metaplasia at the margin of duodenal ulcers.

Duodenal ulcers are associated with gastric metaplasia in the duodenum, both at the ulcer margin and at more distant sites in the duodenal bulb. pS2 and human spasmolytic polypeptide (hSP) are secretory peptides expressed in gastric epithelial cells and in gastric metaplasia. As these peptides may be important in ulcer healing, this study investigated the possibility that the expression of pS2 and hSP is increased in gastric metaplasia at the margin of duodenal ulcers. Duodenal bulb biopsy specimens from 12 duodenal ulcer patients were assessed. Sections were immunostained with monoclonal antibodies for pS2 and hSP. Cytoplasmic stain intensities were measured by an image analysis system and expressed as integrated optical density (IOD) units, In situ hybridisation for pS2 and hSP mRNA was carried out on parallel sections. Duodenal sections were also stained with diatase periodic acid Schiff/alcian blue to localise areas of gastric metaplasia. pS2 antigen staining in the duodenum was restricted to surface epithelial cells, and hSP to acinar and ductular components of Brunner's gland. mRNA localisation corresponded to immunostaining cells. In gastric metaplasia, pS2 expression was greater at the ulcer margin than away from the ulcer, as judged by the intensity of antibody staining (mean IOD units (SEM), 20.6 (3.3) v 9.5 (3.0); p < 0.001). There was a trend towards greater hSP staining at the ulcer margin but this did not achieve statistical significance. These findings support the putative role of pS2 and possible hSP in mucosal healing and providy further evidence for an autocrine 'ulcer-gastric metaplasia-repair' loop involving these trefoil peptides.

Brunner Glands↗

Helicobacter pylori infection density and gastric inflammation in duodenal ulcer and non-ulcer subjects.

The factors that determine which Helicobacter pylori infected subjects develop duodenal ulcer (DU) are unclear. This study tested the hypothesis that infection density and urease activity are higher in DU than non-DU subjects. Fifty five DU and 55 age and sex matched non-DU subjects were studied. Quantitative methods were used for measuring infection density (viable organism count) and urease activity (Berthelot reaction). DU subjects had a greater antral infection density (geometric mean of colony forming units/mg biopsy protein; 10.5 x 10(5) v 1.3 x 10(5), p < 0.001). They also had higher biopsy urease activity (geometric mean of NH3 nmol/min-1/mg protein-1; 103 v 25, p < 0.001). Urease activity per organism, however, was similar in the two groups showing that high antral urease activity in DU was a reflection of organism density. DU was not present in subjects with an antral infection density less than 10(5) colony forming units/mg protein. A correlation was present between H pylori viable counts and the severity and activity of gastritis. Both severity and activity of gastritis were greater in the antrum of DU compared with non-DU subjects but there was no difference in the body between the two groups. It is concluded that antral H pylori infection density is probably an important determinant of DU development, and that there is a baseline of infection density that is necessary for ulcer formation.

Adult↗