Search PubMedSearch

Biomedical subjects

J R Lambert

Publications and source records attributed to J R Lambert.

At least 19 recordsLinked to original sources

Steroid-selective initiation of chromatin remodeling and transcriptional activation of the mouse mammary tumor virus promoter is controlled by the site of promoter integration.

The mouse mammary tumor virus (MMTV) promoter has target sequences recognized by several steroid receptors. We present evidence for a novel mechanism that confers hormone specificity to this promoter. We show that remodeling of MMTV chromatin and the concomitant activation of the MMTV promoter are induced equally by glucocorticoids and progestins in one chromosomal context but are selective for glucocorticoids in another. Furthermore, increased histone acetylation modulates MMTV promoter regulation disparately at the two chromosomal locations. Together, these data indicate that chromosomal architecture commands a crucial role in gene regulation, imposing locus-specific selectivity between regulators with similar sequence recognition.

Acetylation

An evaluation of whole blood testing for Helicobacter pylori in general practice.

BACKGROUND: Rapid whole blood tests for Helicobacter pylori infection were developed to assist in the management of patients with dyspepsia in general practice. However, they have not been extensively tested in this setting. AIM: To investigate the test characteristics of the BM-Test (Helisal Quick Test) when used in general practice. METHOD: One hundred and ten dyspeptic patients attending local general practitioners were recruited into the study. The BM-Test was administered by the general practitioner at the screening visit according to standard instructions supplied with the test kit. The patient was then referred to Nepean or Mornington Peninsula Hospitals for further assessment. including a 14C-urea breath test. The test kit was forwarded to the appropriate hospital centre for an independent, blinded reading. The sensitivity and specificity of the BM-Test were evaluated against the results of the 14C-UBT. RESULTS: Based on general practitioner readings, the BM-Test had a sensitivity of 59.3% and a specificity of 90.2%. The positive and negative predictive values were 87.5% and 65.7%, respectively. When based on independent readings, sensitivity rose to 71.2% and specificity fell to 88.2%. The BM-Test was more sensitive for older patients than for younger patients when based on both the general practitioner and independent readings. CONCLUSION: The BM-Test performs below the generally recommended sensitivity and specificity of 90% required for clinical practice.

Adult

Oral treatment schedules for onychomycosis: a study of patient preference.

BACKGROUND: An improved understanding of patients' attitudes to medication may help promote compliance with oral medications for onychomycosis. This study was performed to assess patients' preference between continuous and intermittent oral treatment schedules for onychomycosis and to determine the reasons underlying the selections made. METHODS: Patients were eligible for inclusion if they had current onychomycosis and were willing to take oral medication for this condition. In a 30-min, face-to-face interview, each patient answered questions about four possible treatment schedules for onychomycosis; regimen 1--continuous (daily regular intake) for 12 weeks; regimen 2--intermittent 1 week/month for 3 months (last week of therapy is week 9); regimen 3--intermittent once weekly for 21 weeks; regimen 4--intermittent 1 week/month for 4 months (last week of therapy is week 13). RESULTS: A total of 102 patients from Germany and Spain participated in the study. When asked to choose between regimens 1, 2, and 3, 46% of patients favored the 9-week intermittent schedule, 42% selected the 12-week continuous schedule, and 12% preferred the 21-week intermittent schedule. The preference for the 9-week intermittent schedule was more notable among younger patients (< 45 years), possibly because they are less used to taking regular medication, and among Spanish patients, an effect that could not be attributed to age because the average age of patients was similar in the participating countries (Germany 47.2 years; Spain 48.0 years). When the patients who preferred regimen 2 were asked to choose between regimens 1, 3, and 4 (both intermittent schedules longer than the continuous schedule), most (57%) favored the shortest treatment schedule (regimen 2). CONCLUSIONS: Overall, patients favored an intermittent schedule lasting 9 weeks. Treatment duration is the critical factor in determining patients' preference for treatment schedules for onychomycosis.

Administration, Oral

Prevalence of Helicobacter pylori in a representative Anglo-Celtic population of urban Melbourne.

The aims of this study were to assess the prevalence of Helicobacter pylori and its relationship with different epidemiological factors in an Anglo-Celtic Australian population in the Melbourne urban area. Two hundred and seventy-three (120 men and 153 women with a mean age of 55.6 and range of 20 to 80 years) of 396 eligible subjects randomly sampled from the telephone directory were studied. An ELISA technique was used to detect H. pylori immunoglobulin (Ig)G antibody and self-administered questionnaires were completed. The overall seroprevalence of H. pylori was 38% and increased with age from 18% (20-30 years old) to 53% (over 70 years; P < 0.0001). The acquisition of H. pylori infection was 1% per year. The prevalence of H. pylori was 48% in men and 30% in women (P < 0.01). The frequency of H. pylori was also associated with low-income levels and current smoking, but was not associated with peptic ulcer disease history. The prevalence of H. pylori infection in a representative Australian population was found to be similar to other developed countries. The risk factors for H. pylori infection include age, male sex, low household income and a smoking habit. No correlation between H. pylori status and dyspepsia symptoms were observed.

Adult

The impact of Helicobacter pylori eradication on peptic ulcer healing.

OBJECTIVE: Current literature was reviewed analyzing the outcome of peptic ulcer healing in relation to the results of the posttherapeutic Helicobacter pylori (HP) status. METHODS: Literature was reviewed along with an analysis of 60 studies, comprising a total of 4329 patients. RESULTS: Successful Helicobacter pylori eradication was found to induce a better response in peptic ulcer healing, regardless of diagnosis: gastric ulcer 88% vs 73% (odds ratio [OR] 2.7, p < 0.01), duodenal ulcer 95% vs 76% (OR 5.6, p < 0.0001), and peptic ulcer 95% vs 76% (OR 6.6, p < 0.0001), for patients having their HP infection successfully cured versus those remaining HP-positive, respectively (Fisher's exact test). For all evaluated time points (< or = 6, 7-8, and 10-12 wk after beginning treatment), HP-negative patients had higher healing rates than HP-positive patients (95% vs 82%, 94% vs 69%, and 96% vs 78% with corresponding OR of 4.2, 6.5, and 7.4, all p < 0.0001, Fisher's exact test). The use of concomitant acid suppression therapy during initial HP eradication provided a benefit on peptic ulcer healing only for patients with persistent HP infection (improved healing rates of 78% vs 67%; otherwise rates were 94-96%). Likewise, prolonged acid inhibition in HP treatment failures after the initial HP treatment phase resulted in 7-20% improved healing rates, whereas patients becoming HP-negative did not profit. CONCLUSION: Successful HP eradication therapy accelerates peptic ulcer healing even without concomitant acid suppression.

2-Pyridinylmethylsulfinylbenzimidazoles

Helicobacter pylori as a pathogenic factor in Ménétrier's disease.

The cause of Ménétrier's disease is unknown, although various autoimmune, allergic, and infective causes have been postulated. This case report describes a 37-yr-old man with Ménétrier's disease associated with protein-losing enteropathy and Helicobacter pylori infection. Clinical, endoscopic, histological, and biochemical resolution occurred after treatment of Helicobacter pylori infection. The improvement observed in this case supports an etiological role for H. pylori infection in Ménétrier's disease.

Adult

The prevalence of Helicobacter pylori in practising dental staff and dental students.

Recent studies suggest Helicobacter pylori is spread by faecal-oral or oral-oral transmission. Gastroenterologists who are exposed to gastric secretions and saliva have a high prevalence of H. pylori infection. Venous blood was obtained from 92 dentists, 40 dental nurses, 33 fifth year and 30 first year dental students. An ELISA assay was used to detect H. pylori IgG antibodies. Results were compared with an age and sex matched normal population. The prevalence of H. pylori infection in dentists, dental nurses, fifth year dental students and first year dental students were 23 per cent, 18 per cent, 18 per cent and 16 per cent, respectively. There were no significant differences when compared with the normal population controls. The prevalence of H. pylori antibody was not significantly increased with years of practice or patient contact time in dentists and dental nurses. Helicobacter pylori infection is uncommon in dental professionals working in the oral cavity.

Adolescent

Novel bismuth compounds have in vitro activity against Helicobacter pylori.

The increasing antimicrobial resistance in Helicobacter pylori has led to the search for new therapeutic agents. In this in vitro study, novel compounds combining bismuth with sialic acid inhibitors were investigated for bactericidal activity using time-kill methodology. The activity of these compounds was compared to bismuth subcitrate against a type strain and a clinical isolate of H. pylori. The compounds tested showed cidal activity which was related to the bismuth component of each drug. These compounds may offer a potential advantage over current bismuth preparations with the sialic acid inhibitor moiety interfering with adhesion of H. pylori to gastric epithelium.

Bacterial Adhesion

Dyspepsia due to eosinophilic gastroenteritis.

Classical eosinophilic gastroenteritis is a rare disease but may be misdiagnosed in clinical practice. We report eosinophilic gastroenteritis that was diagnosed in six patients (four males and two females; mean age 31.5 years) using standard criteria (presence of gastrointestinal symptoms, a predominant eosinophilic infiltrate on biopsy, and exclusion of other causes of eosinophilia). All had gastric mucosal disease and presented with dyspepsia. The median duration of symptoms prior to diagnosis was three months (range five weeks to 13 years). Epigastric pain or discomfort was the most common symptom (100%) followed by anorexia, nausea, and vomiting (67%, 67% and 33%, respectively). None had diarrhea. Half the patients had a history of allergy, while 67% had peripheral eosinophilia. All responded to oral steroids within two months; one third needed to continue on a small dose of maintenance steroids to remain in remission. A high degree of suspicion and biopsy at upper endoscopy is necessary for diagnosis of this rare disease.

Adolescent

The actions of bismuth in the treatment of Helicobacter pylori infection.

Bismuth salts have been used in medicine for over three centuries, particularly in the treatment of dyspepsia. Commonly used agents include colloidal bismuth subcitrate (CBS), bismuth subsalicylate (BSS) and the newer ranitidine bismuth citrate (RBC). These are safe drugs which exert local effects on the gastroduodenal mucosa. Gastric mucosal levels of bismuth exceed the concentrations required to kill Helicobacter pylori in vitro. The mechanisms of actions of bismuth on gastrointestinal pathogens including H. pylori are complex and include inhibition of protein and cell wall synthesis, membrane function and ATP synthesis. Adherence of H. pylori to surface epithelial cells is also impaired. Bismuth monotherapy is effective in vivo to suppress H. pylori but cure rates are low. CBS, BSS and RBC have synergistic activity with one or two antibiotics and are effective in eradicating H. pylori. CBS and RBC also exert other effects on the mucosa including cytoprotective and ulcer healing properties. In addition, RBC is effective in inhibiting gastric acid secretion.

Anti-Bacterial Agents

Antimicrobial resistance testing of Helicobacter pylori: a comparison of Etest and disk diffusion methods.

Routine antimicrobial resistance testing of Helicobacter pylori is more commonly performed since the correlation between metronidazole resistance and failure to eradicate using this drug, has been made. While resistance testing of H. pylori by Etest is simple to perform, it is expensive compared to disk diffusion methods. In this study the Etest was compared with a modified Kirby-Bauer disk diffusion (NCCLS) method for routine resistance screening of H. pylori. Fifty one pre-treatment isolates were tested against amoxycillin, metronidazole, tetracycline and erythromycin by both Etest and disk diffusion using NCCLS guideline strength disks. Clarithromycin was tested by Etest only. Nitroimidazole and macrolide resistance were detected using the modified Kirby-Bauer disk diffusion method which correlated with Etest minimum inhibitory concentration (MIC). Resistance rates were 49% for metronidazole and 8% for clarithromycin. Cross resistance occurs with macrolides against H. pylori and allows testing of erythromycin to predict resistance to clarithromycin. The very low MICs obtained with H. pylori against amoxycillin and tetracycline require the use of Etest or lower strength disk methods to be used.

Amoxicillin

Bactericidal activity and synergy studies of proton pump inhibitors and antibiotics against Helicobacter pylori in vitro.

The bactericidal activity of the proton pump inhibitors omeprazole and lansoprazole alone and in combination with a beta-lactam or macrolide antibiotic were investigated in vitro. Time-kill curves against Helicobacter pylori NCTC 11637 and a recent clinical isolate revealed significant concentration-dependent killing with all drugs other than amoxycillin. Combinations of proton pump inhibitor and erythromycin showed synergic activity. In contrast, proton pump inhibitor plus amoxycillin showed additive activity against the clinical isolate only. Bactericidal investigations of anti-helicobacter drugs in vitro may suggest optimum treatment strategies for this common infectious disease.

2-Pyridinylmethylsulfinylbenzimidazoles

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