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Biomedical subjects

J R Lambert

Publications and source records attributed to J R Lambert.

At least 37 records · Page 2Linked to original sources

Deep cerebral invasion by basal cell carcinoma of the scalp.

We report recurrent basal cell carcinoma of the scalp with deep cerebral invasion in an 82-year-old man. Plain films and CT showed extensive, full thickness, skull destruction at the vertex. Gadolinium-enhanced MRI revealed neoplastic invasion of the meninges and left cerebral hemisphere, down to the lateral ventricle. We postulate that tumour extended into the brain along perivascular spaces of transcerebral vessels. This hypothesis is supported by the cleft-like contrast enhancement on MRI.

Aged↗

Metronidazole resistance: a predictor of failure of Helicobacter pylori eradication by triple therapy.

Triple therapy (bismuth and two antibiotics) will eradicate Helicobacter pylori infection in 70-90% of subjects. Treatment failure has been attributed to patient compliance and antimicrobial drug resistance. The aim of this study was to examine factors influencing the eradication of H. pylori following triple therapy. Thirty seven subjects with H. pylori cultured from antral biopsies were treated with colloidal bismuth subcitrate (120 mg qid for 2 weeks), metronidazole (400 mg tid for 1 week) and amoxycillin (500 mg tid for 1 week). Pretreatment isolates of H. pylori were tested for metronidazole susceptibility by agar dilution according to the National Committee for Clinical Laboratory Standards guidelines. Factors including age, sex, clinical diagnosis and metronidazole resistance were evaluated in relation to H. pylori. The overall metronidazole resistance was 32%. Metronidazole resistant strains were more frequent in females, with a resistance rate of 54%. Helicobacter pylori eradication occurred in 68% of patients with a metronidazole susceptible stain and only 17% of patients with a metronidazole resistant strain (P < 0.03). Helicobacter pylori eradication is dependent upon susceptibility to metronidazole. This data would support the role for routine metronidazole susceptibility testing using appropriate standardized methods when triple therapy is to be considered.

Amoxicillin↗

Oxygen concentration influences proton pump inhibitor activity against Helicobacter pylori in vitro.

Omeprazole and lansoprazole are proton pump inhibitors that have shown activity against Helicobacter pylori and other Helicobacter species when tested by agar dilution. Lansoprazole was more active against H. pylori than was omeprazole, and the activity was independent of urease production. Disk susceptibility tests and agar dilution MIC determinations were performed to investigate the effects of incubation under different sets of atmospheric conditions on H. pylori inhibition. Oxygen concentration was found to influence proton pump inhibitor activity in vitro, with higher concentrations leading to greater susceptibility. The method of testing is important in determining the anti-Helicobacter activity of proton pump inhibitors.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Helicobacter pylori and gastric neoplasia: evolving concepts.

There is evidence that Helicobacter pylori infection is associated with gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma and possibly with non-ulcer dyspepsia. Eradication therapy for confirmed H. pylori infection may therefore become mandatory in patients with non-ulcer dyspepsia severe enough to warrant endoscopy and in first-degree relatives of patients with gastric cancer. However, routine treatment of asymptomatic carriers awaits confirmation of the association with cancer.

Adenocarcinoma↗

Validation of a modified Kirby-Bauer disk diffusion method for metronidazole susceptibility testing of Helicobacter pylori.

Triple antimicrobial therapy that includes metronidazole has been recommended as a first-line therapy for Helicobacter pylori because it has the highest eradication rates. However, resistance in H. pylori to metronidazole has been reported worldwide and its presence may reduce the efficacy of triple therapy. Various methods for testing H. pylori against metronidazole have been used including agar dilution, disk diffusion and the Etest but there has been little standardization of methods. One hundred isolates of H. pylori from different patients were tested for susceptibility to metronidazole by agar dilution, Etest and disk diffusion (5 micrograms disk). The agar dilution results confirmed the MIC susceptibility breakpoint to be < or = 8 micrograms/ml. Using this breakpoint there was close agreement (98%) between Etest and agar dilution results. For susceptible strains, MICs by E-test were generally one twofold dilution lower. Using the error-rate bounded method, agreement between disk diffusion zone diameter and MIC was 98% for agar dilution with breakpoints of > or = 12 mm and < or = 8 micrograms/ml and 100% for Etest with breakpoints of > or = 12 mm and < or = 8 micrograms/ml. The Etest discriminated better than agar dilution between susceptible and resistant strains and was simple to perform. The disk diffusion test is a reliable and cheaper alternative to the Etest with susceptibility being a zone diameter > or = 12 mm with a 5 micrograms disk. The prevalence of metronidazole resistance in this study was 40% by Etest.

Diffusion↗

Polymorphic light eruption--an immunopathological study of provoked lesions.

Polymorphic light eruption (PLE) lesions were induced in 26 patients after an average of 60 J total body UVA irradiation. Using the criteria of the French literature, that make a distinction between PLE and benign summer light eruption (BSLE), the group of 26 patients with PLE was divided into 12 patients with BSLE and 14 patients with PLE, on the basis of historical criteria. Biopsies were taken and compared immunohistochemically with biopsies from 15 unirradiated normal control subjects, in order to find evidence in support of the hypothesis that PLE involves a delayed-type hypersensitivity reaction. The provoked lesions showed: ICAM-1 expression on the keratinocytes of the basal and suprabasal cell layers in 18 of 25 patients, i.e. 72%; HLA-DR expression on the keratinocytes of the basal, squamous and granular cell layer in 13 of 25 patients, i.e. 52%; and OKM5 expression on the keratinocytes of the granular cell layer in 13 of 26 patients, i.e. 50% of the cases. The control samples showed no such antigen expression on the keratinocytes, except for two cases where weak and very localized ICAM-1 positivity was observed; one of these also had a slight localized positivity for HLA-DR and OKM5. The results of the phototesting procedures and the immunohistochemical investigations were similar in both BSLE and PLE. This suggests that they are the same condition, and the term BSLE should therefore probably be discarded. The results of our investigations support the theory of an immunological basis for PLE.

Adult↗

In vitro inhibition of Helicobacter pylori NCTC 11637 by organic acids and lactic acid bacteria.

In this study the effects of both pH and organic acids on Helicobacter pylori NCTC 11637 were tested. Lactobacillus acidophilus, Lact. casei, Lact. bulgaricus, Pediococcus pentosaceus and Bifidobacterium bifidus were assayed for their lactic acid production, pH and inhibition of H. pylori growth. A standard antimicrobial plate well diffusion assay was employed to examine inhibitory effects. Lactic, acetic and hydrochloric acids demonstrated inhibition of H. pylori growth in a concentration-dependent manner with the lactic acid demonstrating the greatest inhibition. This inhibition was due both to the pH of the solution and its concentration. Six strains of Lact. acidophilus and one strain of Lact. casei subsp. rhamnosus inhibited H. pylori growth where as Bifidobacterium bifidus, Ped. pentosaceus and Lact. bulgaricus did not. Concentrations of lactic acid produced by these strains ranged from 50 to 156 mmol l-1 and correlated with H. pylori inhibition. The role of probiotic organisms and their metabolic by-products in the eradication of H. pylori in vivo remains to be determined.

Acetates↗

Reduced amoxicillin uptake into human gastric mucosa when gastric juice pH is high.

Amoxicillin when administered with gastric acid suppressors has been shown to be effective in eradication of Helicobacter pylori in 50 to 80% of subjects. The aim of this investigator-blind crossover study was to determine if gastric mucosal amoxicillin uptake was affected by increasing gastric juice pH. Fifteen male subjects (7 H. pylori positive and 8 H. pylori negative) were randomized to receive 150 mg of ranitidine twice a day, 300 mg of ranitidine twice a day, or no drug for 2 days prior to upper endoscopy. The last dose of ranitidine was given 60 min prior to upper endoscopy, and amoxicillin (500 mg) was given 30 min prior to upper endoscopy. The amoxicillin concentrations in mucosal biopsy samples, gastric juice, and serum were determined by a standard microbiological bioassay technique. Mean amoxicillin levels were greater in samples of antrum, fundus, and duodenum for volunteers who received no ranitidine than in those receiving 300 mg of ranitidine (P < 0.05) and those receiving 150 mg of ranitidine (P < 0.05 except for fundus). Amoxicillin levels in the antrum, fundus, and duodenum were negatively correlated with gastric juice pH (P < 0.005 for antrum; P < 0.001 for fundus and duodenum). There was no correlation between gastric juice pH and amoxicillin levels in either gastric juice or serum. The amoxicillin concentration in gastric juice was significantly higher with 300 mg of ranitidine than with no ranitidine (P < 0.05). Thus, lower gastric juice pH is associated with a higher rate of mucosal uptake of amoxicillin.

Adolescent↗

Cytotoxin production by Helicobacter pylori from patients with upper gastrointestinal tract diseases.

A cytotoxin produced by some Helicobacter pylori strains has recently been identified. The cytotoxin induces intracellular vacuolization of cultured cells. The aim of the present study was to examine the frequency of occurrence of cytotoxin-producing strains of H. pylori from subjects with upper gastrointestinal disease including nonulcer dyspepsia, gastric and duodenal ulcer disease, gastroesophageal reflux disease, and gastric cancer. Broth culture filtrates of clinical isolates of H. pylori recovered from 175 patients were used to inoculate Vero and HeLa cell monolayers for the detection of vacuolating cytotoxin activity. The results obtained demonstrated that the highest percentage of strains producing cytotoxin were found in subjects with peptic ulcer disease (gastric ulcer, 65%; duodenal ulcer, 66%; P < 0.01 compared with nonulcer dyspepsia, 38%). Of the 11 patients with gastroesophageal reflux disease, 4 of 5 patients in this group who had esophageal ulcers, were found to be infected with strains that produced cytotoxin. Three of the four patients with carcinoma of the stomach were also found to be infected with cytotoxic strains of H. pylori. With increasing severity of mucosal damage in subjects with a normal upper gastrointestinal tract, macroscopic gastritis, duodenitis, and peptic ulceration, there were corresponding increase in the proportion of strains producing cytotoxin; these increases were 32, 46, 50, and 66%, respectively. H. pylori strains from subjects with ulcer disease commonly produced vacuolating cytotoxin, suggesting that it may be a virulence factor in the pathogenesis of peptic ulcer disease.

Animals↗

A practical single sample dry latex agglutination test for Helicobacter pylori antibody detection.

Assessment of a single serum sample for Helicobacter pylori antibodies is frequently requested in routine diagnostic laboratories. Current enzyme linked immunosorbent assay (ELISA) kits are not ideal for testing small numbers of serum samples and some have low sensitivities, specificities or large grey zones. A panel of 90 serum samples from patients who had presented for routine upper endoscopy was used to compare three kits for the detection of H pylori antibodies: (1) Pyloriset Dry, total antibody latex agglutination, Orion Diagnostica, Espoo, Finland; (2) Pyloriset enzyme immunoassay (EIA), IgG ELISA, Orion; and (3) Hel-p, IgG ELISA, Amrad, Kew, Victoria, Australia. Diagnosis of H pylori positivity was made if culture results and either rapid urease test or histopathology were positive. The sensitivity, specificity, positive, and negative predictive value for each test was as follows: Orion: latex 93.3%, 95.6%, 95.5%, 93.3%, respectively; Orion: EIA-G 84.4%, 97.8%, 97.4%, 84.4%, respectively; and Amrad: EIA-G 100%, 88.9%, 90%, 100%, respectively. The latex test performed better than the EIAs with respect to sensitivity and specificity.

Adult↗

Helicobacter pylori.

Helicobacter pylori is an important cause of chronic active gastritis and is strongly associated with peptic ulcer disease and gastric cancer. H. pylori colonizes the surface of the gastric epithelium with production of a number of factors, resulting in inflammation and an altered mucosa. H. pylori infection occurs world-wide and the mode of transmission most likely is from human to human via the fecal-oral and/or the oral-oral route. Treatment and, in the future, prevention of this infection may result in a marked diminution of upper gastrointestinal tract disease.

Animals↗

High prevalence of Helicobacter pylori antibodies in an institutionalized population: evidence for person-to-person transmission.

OBJECTIVE: To evaluate the prevalence of H. pylori antibodies in mentally and physically handicapped adults living together in a long-term care facility. METHODS: One hundred twenty-two institutionalized subjects from six living areas were compared to a normal representative Caucasian population obtained by random sampling from the urban population area of Melbourne. Serum samples from 1977 and 1989 from 122 subjects were tested for H. pylori antibody by an ELISA technique. The data were analyzed by Student's t test, chi 2 test and logistic regression. RESULTS: Ninety-two of the 122 subjects (75%) from whom sera was collected in 1989 were seropositive for H. pylori, compared with only 23% in age- and sex-matched control subjects (p < 0.0001). The prevalence of H. pylori antibodies in 1977 was 34% (42/122). Of the remaining 80 seronegative subjects, 51 (61.4%) converted to became positive in the 12-yr interval. The annual seroconversion rate was 7.4%, with an average of 4.25 newly positive subjects each year. The prevalence of H. pylori in 1989 was significantly higher than in 1977 after adjustment for age (odds ratio 2.39, 95% CI 1.1-5.3, p = 0.03). CONCLUSIONS: H. pylori antibodies are significantly more prevalent in institutionalized adults compared with controls from the general population. These data support the hypothesis that H. pylori is acquired by either fecal-oral or oral-oral transmission.

Adult↗

Helicobacter pylori in ulcerogenesis.

Patients with peptic ulcer disease have elevated gastric acid secretion, hyperfunction of G cell, impaired bicarbonate secretion, increased levels of pepsinogen I and the presence of inflammatory mediators as well as Helicobacter pylori-induced gastroduodenitis and gastric metaplasia in the duodenum (in duodenal ulcer patients). Non-H. pylori-associated ulcers include those due to non-steroidal anti-inflammatory drugs, Zollinger-Ellison syndrome, and those related to other forms of gastritis. Evidence of H. pylori in ulcerogenesis includes the higher prevalence of H. pylori in gastritis and peptic ulcer patients plus the important observation that H. pylori eradication results in healing and long-term cure of ulcer disease. The precise mechanism of mucosal injury and ulceration is unclear. Bacterial and inflammatory factors are involved as well as host changes in hormones and gastric acid secretion.

Anti-Bacterial Agents↗

The ORD1 gene encodes a transcription factor involved in oxygen regulation and is identical to IXR1, a gene that confers cisplatin sensitivity to Saccharomyces cerevisiae.

The yeast COX5a and COX5b genes encode isoforms of subunit Va of the mitochondrial inner membrane protein complex cytochrome c oxidase. These genes have been shown to be inversely regulated at the level of transcription by oxygen, which functions through the metabolic coeffector heme. In earlier studies we identified several regulatory elements that control transcriptional activation and aerobic repression of one of these genes, COX5b. Here, we report the isolation of trans-acting mutants that are defective in the aerobic repression of COX5b transcription. The mutants fall into two complementation groups. One group specifies ROX1, which encodes a product reported to be involved in transcriptional repression. The other group identified the gene we have designated ORD1. Mutations in ORD1 cause overexpression of COX5b aerobically but do not affect the expression of the hypoxic genes CYC7, HEM13, and ANB1. ORD1 mutations also do not affect the expression of the aerobic genes COX5a, CYC1, ROX1, ROX3, and TIF51A. The yeast genome contains a single ORD1 gene that resides on chromosome XI. Strains carrying chromosomal deletions of the ORD1 locus are viable and exhibit phenotypes similar to, but less severe than, that of the original mutant. The nucleotide sequence of ORD1 revealed that it is identical to IXR1, a yeast gene whose product contains two high mobility group boxes, binds to platinated DNA, and confers sensitivity to the antitumor drug cisplatin. Consistent with the latter observations, we found that the ORD1 product could bind to both the upstream region of COX5b and to DNA modified with cisplatin.

Amino Acid Sequence↗