Biomedical subjects

David A Cairns

Publications and source records attributed to David A Cairns.

3 recordsLinked to original sources

PubMed2006

Urinary biomarker profiling in transitional cell carcinoma.

Urinary biomarkers or profiles that allow noninvasive detection of recurrent transitional cell carcinoma (TCC) of the bladder are urgently needed. We obtained duplicate proteomic (SELDI) profiles from 227 subjects (118 TCC, 77 healthy controls and 32 controls with benign urological conditions) and used linear mixed effects models to identify peaks that are differentially expressed between TCC and controls and within TCC subgroups. A Random Forest classifier was trained on 130 profiles to develop an algorithm to predict the presence of TCC in a randomly selected initial test set (n = 54) and an independent validation set (n = 43) several months later. Twenty two peaks were differentially expressed between all TCC and controls (p < 10(-7)). However potential confounding effects of age, sex and analytical run were identified. In an age-matched sub-set, 23 peaks were differentially expressed between TCC and combined benign and healthy controls at the 0.005 significance level. Using the Random Forest classifier, TCC was predicted with 71.7% sensitivity and 62.5% specificity in the initial set and with 78.3% sensitivity and 65.0% specificity in the validation set after 6 months, compared with controls. Several peaks of importance were also identified in the linear mixed effects model. We conclude that SELDI profiling of urine samples can identify patients with TCC with comparable sensitivities and specificities to current tumor marker tests. This is the first time that reproducibility has been demonstrated on an independent test set analyzed several months later. Identification of the relevant peaks may facilitate multiplex marker assay development for detection of recurrent disease.

Adult↗

PubMed2005

Influences of blood sample processing on low-molecular-weight proteome identified by surface-enhanced laser desorption/ionization mass spectrometry.

BACKGROUND: Profiling approaches in proteomics, such as surface-enhanced laser desorption/ionization (SELDI) mass spectrometry, are used in disease marker discovery. The aim of this study was to investigate the potential influence of selected preanalytical factors on the results obtained. METHODS: Plasma samples anticoagulated with EDTA, citrate, or heparin, and serum samples from healthy volunteers were profiled by SELDI on CM10, immobilized metal affinity capture (IMAC) array with copper, and H50 chip surfaces. Using linear mixed-effects models, we examined the influence of elapsed time between venipuncture and sample separation (immediate to 24 h) and the type of serum tube used (Greiner Vacuette activator, gel serum separator, or plain tubes). We analyzed purified platelets, as well as platelet-poor and platelet-rich plasma samples treated with calcium and/or thrombin to determine the platelet contribution, directly or via the clotting process, to the profiles generated. We then used cluster analysis to identify samples with similar peak profiles. RESULTS: Different plasma types and sera could be distinguished on the basis of cluster analyses of their spectral profiles. Elapsed time between venipuncture and separation of plasma and serum from blood samples altered the profiles obtained, particularly for serum samples and particularly on IMAC chips. The type of serum collection tube also affected the profiles because of differences in clotting time. In vitro manipulation of platelets revealed that specific peaks in IMAC profiles of serum appeared to be derived directly from platelets. Several other peaks, including some of those exhibiting time-dependent changes, arose during the clotting process. CONCLUSION: Preanalytical variables, such as sample handling, can markedly influence results.

Adult↗

PubMed2004

Primary nonoperative treatment of displaced lateral fractures of the clavicle.

BACKGROUND: The optimal management of displaced fractures of the lateral end of the clavicle remains controversial. Successful results have been reported both with primary open reduction and internal fixation and with nonoperative treatment. The purpose of this study was to analyze the results of employing a policy of primary nonoperative treatment of displaced lateral fractures of the clavicle. METHODS: We treated a cohort of 127 patients who had sustained a displaced fracture of the lateral end of the clavicle. With the exception of seven patients who had immediate internal fixation, all of these patients were treated nonoperatively. At the time of follow-up, nineteen patients had died or could not be traced and fifteen were interviewed by telephone only. The remaining eighty-six patients were assessed clinically at an average of 6.2 years after the injury. All of these patients had a functional evaluation and were assessed radiographically. RESULTS: Fourteen (14%) of the 101 patients who could be contacted had had symptoms severe enough to warrant delayed surgical intervention (Group I). The remaining eighty-seven patients had not undergone any surgery, and twenty-one of them (21% of the whole cohort) had a nonunion of the clavicular fracture. The average Constant score in the nonoperatively treated group was 93 points (range, 82 to 98 points). With the numbers available, there was no significant difference in the Constant or Short Form-36 (SF-36) scores between the patients with nonunion (Group II) and those in whom the fracture had healed (Group III) or between the patients who had been treated nonoperatively (Groups II and III) and those who had had delayed surgery (Group I). There was no significant difference between the SF-36 scores in any of the groups and the scores for age-matched controls in the general population. CONCLUSIONS: Nonoperative treatment of most displaced lateral fractures of the clavicle in middle-aged and elderly patients achieves a good medium-term functional result. Symptoms that were severe enough to warrant a delayed reconstructive procedure developed in only 14% of the patients. Asymptomatic nonunion does not appear to adversely affect the functional outcome in the medium term.

Adolescent↗