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Biomedical subjects

L Roberts

Publications and source records attributed to L Roberts.

At least 37 records · Page 2Linked to original sources

Mammaglobin is found in breast tissue as a complex with BU101.

The mammaglobin gene has been shown to be preferentially expressed in breast tissue. Few genes match its specificity. Mammaglobin has generated much interest, and studies are ongoing to develop diagnostic tests for breast cancer based on the detection of mammaglobin. While searching the Incyte Genomics Lifeseq database for tissue-specific markers, we observed a second secretoglobin, BU101, also known as lipophilin B. We report here that mammaglobin, in breast tissue, is found as a complex with BU101. The complex was isolated from breast cancer tissue and was characterized as the biologically relevant form of mammaglobin.

Amino Acid Sequence↗

Randomised controlled trial of Helicobacter pylori testing and endoscopy for dyspepsia in primary care.

OBJECTIVE: To determine the cost effectiveness of a strategy of near patient Helicobacter pylori testing and endoscopy for managing dyspepsia. DESIGN: Randomised controlled trial. SETTING: 31 UK primary care centres. PARTICIPANTS: 478 patients under 50 years old presenting with dyspepsia of longer than four weeks duration. INTERVENTIONS: Near patient testing for H pylori and open access endoscopy for patients with positive results. Control patients received acid suppressing drugs or specialist referral at general practitioner's discretion. MAIN OUTCOME MEASURES: Cost effectiveness based on improvement in symptoms and use of resources at 12 months; quality of life. RESULTS: 40% of the study group tested positive for H pylori. 45% of study patients had endoscopy compared with 25% of controls. More peptic ulcers were diagnosed in the study group (7.4% v 2.1%, P=0.011). Paired comparison of symptom scores and quality of life showed that all patients improved over time with no difference between study and control groups. No significant differences were observed in rates of prescribing, consultation, or referral. Costs were higher in the study group ( 367.85 pound sterling v 253.16 pound sterling per patient). CONCLUSIONS: The test and endoscopy strategy increases endoscopy rates over usual practice in primary care. The additional cost is not offset by benefits in symptom relief or quality of life.

Adolescent↗

Multilocus linkage analysis of the German asthma data.

We analyzed data from the German Asthma Genetics Group with three methods that utilize pedigree-specific nonparametric linkage scores to facilitate the search for multiple independent and interacting susceptibility loci. The three methods included a conditional analysis, logistic regression, and neural networks. Although there were differences, the three methods identified many of the same susceptibility loci. The most consistent evidence was provided for loci on chromosomes 1, 2, 6, 9, and 15. Both the conditional and the logistic regression analyses suggested an epistatic relationship between loci on chromosomes 2 and 9. The logistic regression analysis further revealed evidence for locus heterogeneity between loci on chromosomes 6 and 15. Finally, the neural network analysis identified a potential locus on chromosome 17 that was not identified in the other analyses.

Adult↗

Improved respiratory delivery of the anticancer drugs, camptothecin and paclitaxel, with 5% CO2-enriched air: pharmacokinetic studies.

PURPOSE: To increase pulmonary deposition of anticancer liposome aerosols in mice by modulation of respiratory physiology through the addition of 5% CO2 to the air source used to generate the aerosols. Breathing CO2-enriched aerosol increases pulmonary ventilation with concurrent increased deposition of inhaled particles. METHODS: Dilauroylphosphatidylcholine liposome formulations of two anticancer drugs, paclitaxel (PTX) and camptothecin (CPT), were investigated. The aerosol droplet size was measured using an Andersen cascade impactor. Drug concentrations in aerosol droplet fractions and tissues were determined by HPLC analysis. ICR mice were exposed to each liposome aerosol for 30 min. For each drug, one group of mice inhaled the drug-liposome aerosol generated with a mixture of 5% CO2 in air and another group inhaled the drug-liposome aerosols produced with normal air. Tissue distribution and pharmacokinetics were determined for both drug delivery systems. RESULTS: Significantly higher concentrations of PTX and CPT were found in organs of mice exposed to 5% CO2-air aerosols compared to organs of mice exposed to normal air aerosols. The highest concentrations of drug were detected in the lungs and were two- to fourfold higher with 5% CO2-air aerosols than with aerosols generated with normal air. Higher concentrations were also detected in liver, spleen, kidneys, blood, and brain. CONCLUSION: 5% CO2 enrichment of air increased respiratory tract deposition of inhaled aerosol particles containing PTX and CPT.

Administration, Inhalation↗

Liposomal daunorubicin in the treatment of relapsed or refractory non-Hodgkin's lymphoma.

PURPOSE: To assess the efficacy and toxicity of liposomal daunorubicin administered as a two-hour intravenous infusion to patients with relapsed or refractory non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Eligible patients had relapsed or refractory NHL with measurable or evaluable disease, and low grade, select intermediate grade, or mantle cell pathologic types. Prior exposure to an anthracycline or anthracenedione was allowed. Liposomal daunorubicin at a dose of 100 mg/m2 was given intravenously over a minimum of 120 minutes every 3 weeks. as a single agent. RESULTS: Thirty-three patients were accrued: twenty-three (70%) had low-grade histologies; six (18%) had intermediate-grade histologies (follicular large-cell and diffuse small cleaved); and four (12%) patients had mantle-cell lymphoma. Eighteen (55%) had received two or more prior regimens; fourteen (42%) received a prior anthracycline. A median of six cycles of liposomal daunorubicin were administered (range 1-15). Of 31 patients evaluable for response, 2 complete and 10 partial remissions were documented for a major response rate of 39% (95% confidence interval (CI): 22%-58%). The median duration of response was 19.5 months (range 4.3-41.1+). Six responders (50%) had received a prior anthracycline; one responder had mantle-cell histology. The major toxicities were grade 3 or 4 neutropenia in 26 patients (79%), mild to moderate nausea in 22 (67%), and fatigue in 16 (48%). CONCLUSIONS: Liposomal daunorubicin at 100 mg/m2 every three weeks has activity in patients with relapsed or refractory NHL, including patients with prior exposure to an anthracycline. Further studies of liposomal daunorubicin in combination with other agents are warranted.

Adult↗

Post-weaning social isolation of rats leads to an abnormal gait.

The purpose of this study was to further characterize the phenotype of rats that have experienced prolonged postweaning social isolation, a paradigm that produces changes relevant to neuropsychiatric disorders. At weaning, male Wistar rats from three litters were housed socially (n = 12) or in isolation (n = 13) for 10 weeks. Isolated rats could see, hear and smell other rats. A sophisticated analysis of gait revealed that the stride duration was increased in isolates (12%, P = 0.0024) as a result of increased stance duration (18%, P = 0.0005), but there was no difference in vertical reaction force or velocity. Adrenal glands were heavier in isolates (19%, P = 0.0047). There was no difference in cross-sectional area of the brain or lateral ventricles anywhere along the anterior-posterior axis. All experiments and analysis were performed blind to housing condition. This is the first study to demonstrate that socially isolated rats have an abnormal gait. Further analysis, including pharmacological manipulation, is needed in order to understand the nature of the abnormality.

Adrenal Glands↗

Alteration in Kupffer cell function after mild hemorrhagic shock.

Functional changes in Kupffer cells occur after profound hemorrhagic shock. This study was performed to demonstrate if Kupffer cell changes also occur after mild hemorrhagic shock. Sprague-Dawley rats were bled to a systolic blood pressure of 60 to 70 mmHg and resuscitated with Lactated Ringers solution (twice the shed blood volume) after 30 min. Resuscitation produced immediate recovery of blood pressure and allowed long-term recovery of the animals. Sham animals received anesthesia and monitoring only. Thirty minutes after resuscitation, Kupffer cells were isolated by centrifugal elutriation and cultured for 48 h. In Kupffer cells isolated from shocked animals, phorbol ester-stimulated superoxide production increased 7-fold and lipopolysaccharide- (LPS) stimulated prostaglandin E2 (PGE2) production increased 4-fold. Tumor necrosis factor-alpha (TNFalpha) production, on the other hand, was decreased by 50%. A non-significant trend toward increased phagocytosis was also observed, whereas LPS-stimulated nitric oxide production was unchanged. In conclusion, mild hemorrhagic shock produced increases in superoxide and PGE2 production, and decreases in TNFalpha production by Kupffer cells, changes that may be appropriate to defend against the infectious challenges that often follows trauma and hemorrhage.

Animals↗

Cluster randomised controlled trial comparing the effectiveness and cost-effectiveness of two primary care interventions aimed at improving attendance for breast screening.

OBJECTIVES: To examine the effectiveness and cost-effectiveness of two interventions based in primary care aimed at increasing uptake of breast screening. SETTING: 24 General practices with low uptake in the second round of screening (below 60%) in north west London and the West Midlands, UK. Participants were all women registered with these practices and eligible for screening in the third round. METHODS: Pragmatic factorial cluster randomised controlled trial, with practices randomised to a systematic intervention (general practitioner letter), an opportunistic intervention (flag in women's notes prompting discussion by health professionals), neither intervention, or both. Outcome measures were attendance for screening 6 months after the practices had been screened and cost-effectiveness of the interventions. RESULTS: 6,133 Women were included: 1,721 control; 1,818 letter; 1,232 flag; 1,362 both interventions. Attendance data were obtained for 5,732 (93%) women. The two interventions independently increased breast screening uptake in a logistic regression model adjusted for clustering, with the flag (odds ratio (OR) 1.43, 95% confidence interval (95% CI) 1.14 to 1.79; p=0.0019) marginally more effective than the letter (OR 1.31, 95% CI 1.05 to 1.64; p=0.015). Health service costs per additional attendance were 26 pounds (letter) and 41 pounds (flag). CONCLUSIONS: Although both interventions increased attendance for breast screening, the letter was the more cost-effective. Any decision to implement both interventions rather than just the letter will depend on whether the additional (41 pounds) costs are judged worthwhile in terms of the gains in breast screening uptake.

Breast Neoplasms↗

Improving attendance for breast screening among recent non-attenders: a randomised controlled trial of two interventions in primary care.

OBJECTIVES: To examine the effectiveness and cost-effectiveness of two primary care based interventions aimed at increasing breast screening uptake for women who had recently failed to attend. SETTING: 13 General practices with low uptake in the second round of breast screening (below 60%) in north west London and the West Midlands, United Kingdom. Participants were women in these practices who were recent non-attenders for breast screening in the third round. METHODS: Pragmatic factorial randomised controlled trial, with people randomised to a systematic intervention (general practitioner letter), an opportunistic intervention (flag in women's notes prompting discussion by health professionals), neither intervention, or both. Outcome measures were attendance for screening 6 months after randomisation and cost-effectiveness of the interventions. RESULTS: 1,158 Women were individually randomised as follows: 289 control; 291 letter; 290 flag; 288 both interventions. Attendance was ascertained for 1,148 (99%) of the 1,158 women. Logistic regression adjusting for the other intervention and practice produced an odds ratio (OR) for attendance of 1.51 (95% confidence interval (95% CI 1.02 to 2.26; p=0.04) for the letter, and 1.39 (95% CI 0.93 to 2.07; p=0.10) for the flag. Health service costs/ additional attendance were 35 pounds (letter) and 65 pounds (flag). CONCLUSIONS: Among recent non-attenders, the letter was effective in increasing breast screening attendance. The flag was of equivocal effectiveness and was considerably less cost-effective than the letter.

Adult↗

Cost effectiveness of initial endoscopy for dyspepsia in patients over age 50 years: a randomised controlled trial in primary care.

BACKGROUND: Dyspepsia can be managed by initial endoscopy and treatment based on endoscopic findings, or by empirical prescribing. We aimed to determine the cost effectiveness of initial endoscopy compared with usual management in patients with dyspepsia over age 50 years presenting to their primary care physician. METHODS: 422 patients were recruited and randomly assigned to initial endoscopy or usual management. Primary outcomes were effect of treatment on dyspepsia symptoms and cost effectiveness. Secondary outcomes were quality of life and patient satisfaction. Total costs were calculated from individual patient's use of resources with unit costs applied from national data. Statistical analysis of uncertainty on incremental cost-effectiveness ratio (ICER) was done along with a sensitivity analysis on unit costs with cost-effectiveness acceptability curves. FINDINGS: In the 12 months following recruitment, 213 (84%) patients had an endoscopy compared with 75 (41%) controls. Initial endoscopy resulted in a significant improvement in symptom score (p=0.03), and quality of life pain dimension (p=0.03), and a 48% reduction in the use of proton pump inhibitors (p=0.005). The ICER was Pound Sterling1728 (UK Pound Sterling) per patient symptom-free at 12 months. The ICER was very sensitive to the cost of endoscopy, and could be reduced to Pound Sterling165 if the unit cost of this procedure fell from Pound Sterling246 to Pound Sterling100. INTERPRETATION: Initial endoscopy in dyspeptic patients over age 50 might be a cost-effective intervention.

Aged↗