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Biomedical subjects

D J Robertson

Publications and source records attributed to D J Robertson.

14 recordsLinked to original sources

Helicobacter pylori-associated ulcer bleeding: should we test for eradication after treatment?

BACKGROUND: Eradication of Helicobacter pylori after peptic ulcer haemorrhage reduces the risk of recurrence. Because H. pylori treatment is very effective, it is unclear whether testing to confirm eradication is worthwhile. AIMS: To examine whether patients with H. pylori-associated peptic ulcer haemorrhage should be tested for successful eradication after completion of antibiotic therapy. METHODS: A Markov cost-effectiveness model was developed to compare testing vs. non-testing of H. pylori eradication in peptic ulcer haemorrhage. Probability estimates and average costs were derived from published information. RESULTS: Testing for H. pylori eradication resulted in a benefit of 0.07 quality-adjusted life-years and cost 836 US dollars less than the strategy of not confirming eradication. Testing remained the superior strategy when varying the model regarding age, the initial success of eradication, various test and retreatment strategies, and the rate and costs of recurrent bleeding. Assuming a high eradication rate (95%), the test strategy becomes more expensive only if the cost of H. pylori testing reaches 265 US dollars; however, even under these conditions it remains cost-effective. CONCLUSIONS: Patients with H. pylori-associated peptic ulcer bleeding should be tested to confirm eradiation of H. pylori after completion of antibiotic treatment.

Cost-Benefit Analysis↗

Histamine receptor antagonists and incident colorectal adenomas.

BACKGROUND: Prior studies suggest that histamines may modulate the development of colorectal neoplasia. AIM: To assess whether histamine receptor antagonist use was associated with adenoma formation. METHODS: Patients (n = 2366) were drawn from three adenoma chemoprevention trials. All underwent baseline colonoscopy with removal of adenoma(s) and were deemed free of remaining lesions; they were followed with surveillance colonoscopy. Medication use was assessed by questionnaire. Adjusted risk ratios for adenoma formation related to histamine receptor antagonist use (histamine H1 and H2 receptor, H1RA and H2RA) were determined using log linear models. RESULTS: In pooled analyses, H1RA exposure was not associated with subsequent adenoma risk (RR = 1.10; 95% CI 0.97-1.25) or multiple adenoma formation (RR = 0.85; 95% CI 0.67-1.07). H2RA use also was not associated with adenoma (RR = 0.90; 95% CI 0.77-1.06), or multiple adenoma (RR = 0.77; 95% CI 0.57-1.04) in the pooled analyses, but H2RA users in the first trial had a decreased risk of adenoma (RR = 0.70; 95% CI 0.48-1.03) and multiple adenoma (RR = 0.31; 95% CI 0.12-0.79). CONCLUSION: H2RA use was associated with reduced risk for adenoma in one trial, but not in the pooled analyses. Further study would be warranted before undertaking randomized trials of H2RAs for adenoma chemoprevention.

Adenoma↗

Cocaine-responsive gene expression changes in rat hippocampus.

Chronic cocaine use is known to elicit changes in the pattern of gene expression within the brain. The hippocampus plays a critical role in learning and memory and may also play a role in mediating behaviors associated with cocaine abuse. To profile the gene expression response of the hippocampus to chronic cocaine treatment, cDNA hybridization arrays were used to illuminate cocaine-regulated genes in rats treated non-contingently with a binge model of cocaine (45 mg/kg/day, i.p.) for 14 days. Validation of mRNA changes illuminated by hybridization array analysis was accomplished by measuring immunoreactive protein (via specific immunoblots). The induction of protein kinase Calpha, potassium channel 1.1, and metabotropic glutamate receptor 5 seen by hybridization arrays was confirmed at the level of protein. Immunoblot screening of previously described cocaine-responsive genes demonstrated increased levels of protein tyrosine kinase 2, beta-catenin, and protein kinase Cepsilon. While some of these changes exist in previously described cocaine-responsive models, others are novel to any model of cocaine use. The inductions of potassium channel 1.1, protein tyrosine kinase 2 and metabotropic glutamate receptor 5 are novel findings to hippocampal cocaine-responsive gene expression. These proteins have been shown to subserve learning and memory and/or long-term potentiation functions within the hippocampus. Additionally, these genes are known to interact with one another, forming a more complex pattern of gene expression changes. The findings suggest altered expression of genes with a number of different functions in the rat hippocampus after a 'binge' style of non-contingent cocaine administration. These changes in gene expression may play roles in neuronal plasticity and the behavioral phenomena associated with cocaine abuse.

Animals↗

Inflammatory bowel disease in the elderly.

Approximately 15% of all patients with IBD first develop symptoms after age 65. As the number of elderly in the population continues to grow, clinicians should expect to see a greater number of elderly IBD patients. In general, the presenting features of IBD are similar to those encountered in younger patients, but the broad differential diagnosis of colitis in the elderly can make definitive diagnosis more challenging. Although most therapies for IBD have not been studied specifically in the elderly, as a general rule, medical and surgical treatment options are the same regardless of age. Osteoporosis, a condition generally associated with aging, should be managed aggressively in patients with IBD because many older persons already have a substantial baseline risk for accelerated bone loss.

Aged↗

Chronic cocaine-mediated changes in non-human primate nucleus accumbens gene expression.

Chronic cocaine use elicits changes in the pattern of gene expression within reinforcement-related, dopaminergic regions. cDNA hybridization arrays were used to illuminate cocaine-regulated genes in the nucleus accumbens (NAcc) of non-human primates (Macaca fascicularis; cynomolgus macaque), treated daily with escalating doses of cocaine over one year. Changes seen in mRNA levels by hybridization array analysis were confirmed at the level of protein (via specific immunoblots). Significantly up-regulated genes included: protein kinase A alpha catalytic subunit (PKA(calpha)); cell adhesion tyrosine kinase beta (PYK2); mitogen activated protein kinase kinase 1 (MEK1); and beta-catenin. While some of these changes exist in previously described cocaine-responsive models, others are novel to any model of cocaine use. All of these adaptive responses coexist within a signaling scheme that could account for known inductions of genes(e.g. fos and jun proteins, and cyclic AMP response element binding protein) previously shown to be relevant to cocaine's behavioral actions. The complete data set from this experiment has been posted to the newly created Drug and Alcohol Abuse Array Data Consortium (http://www.arraydata.org) for mining by the general research community.

Animals↗

Measles virus and Crohn's disease: a critical appraisal of the current literature.

The etiology of inflammatory bowel disease (IBD) is unknown. Recent reports in the literature have suggested that measles virus, both wild-type and vaccine-attenuated, might be a risk factor for Crohn's disease. We used the well-accepted Bradford-Hill criteria to evaluate the possible causal association between measles and IBD. Although the association may be biologically plausible, the literature lacks consistency, specificity, strength, and dose response. The current literature does not support an association between measles virus and IBD.

Crohn Disease↗

Fundamentals of DNA hybridization arrays for gene expression analysis.

DNA hybridization arrays [also known as macroarrays, microarrays and/or high-density oligonucleotide arrays (Gene Chips)] bring gene expression analysis to a genomic scale by permitting investigators to simultaneously examine changes in the expression of literally thousands of genes. For hybridization arrays, the general approach is to immobilize gene-specific sequences (probes) on a solid state matrix (nylon membranes, glass microscope slides, silicon/ceramic chips). These sequences are then queried with labeled copies of nucleic acids from biological samples (targets). The underlying theory is that the greater the expression of a gene, the greater the amount of labeled target, and hence, the greater output signal. In spite of the simplicity of the experimental design, there are at least four different platforms and several different approaches to processing and labeling the biological samples. Moreover, investigators must also determine whether they will utilize commercially available arrays or generate their own. This review will cover the status of the hybridization array field with an eye toward underlying principles and available technologies. Future developments and technological trends will also be evaluated.

Cluster Analysis↗

Hyoscyamine as a pharmacological adjunct in colonoscopy: a randomized, double blinded, placebo-controlled trial.

OBJECTIVE: Investigators have assessed the utility of antispasmodic agents in colonoscopy, with conflicting results. The aim of this study is to determine the effects of premedication with hyoscyamine, an anticholinergic antispasmodic, on outcomes in colonoscopy. METHODS: A total of 165 patients undergoing elective colonoscopy were randomized in a double blinded fashion to one of three arms: intravenous hyoscyamine (0.25 mg), oral hyoscyamine (0.25 mg), or placebo, administered 20-40 min before colonoscopy. Primary outcome measures included insertion time to cecum, patient's assessment of pain, and physician assessment of spasm. Secondary outcome measures included amount of analgesic medications used, total procedure time, amount and type of pathology visualized, and physician assessment of patient's pain. RESULTS: Bivariate analysis showed no difference between the three groups in insertion time (13.8 min, 14.8 min, and 13.8 min for placebo, intravenous hyoscyamine, and oral hyocyamine, respectively), analgesic medication necessary, or any other primary or secondary outcome variable. Multivariate analysis controlling for potential confounders also failed to demonstrate any differences between the groups. Women had higher procedure duration and analgesic requirement, and reported more pain than did men. CONCLUSIONS: This randomized, double blinded, placebo-controlled trial did not demonstrate efficacy of either intravenous or oral hyoscyamine as a premedication for colonoscopy.

Administration, Oral↗