Biomedical subjects

S E Sinclair

Publications and source records attributed to S E Sinclair.

10 recordsLinked to original sources

PubMed2005

Neoadjuvant taxanes in the treatment of non-metastatic breast cancer: a systematic review.

In recent years the role of neoadjuvant (primary, preoperative) chemotherapy has undergone rapid progress. Initially, neoadjuvant chemotherapy use was limited to those patients with inoperable locally advanced breast cancer in an attempt to try to down-size the tumour to make effective surgery possible. The advent of more effective chemotherapy regimens has led to an increased use of neoadjuvant therapy to shrink potentially operable tumours to allow for breast conservation when a mastectomy would have been required previously. While neoadjuvant treatment for operable tumours has indeed allowed increased rates of breast conserving surgery, it has not yet demonstrated any survival benefit over standard postoperative anthracycline-based chemotherapy. Echoing the evolution of taxane based chemotherapy from the metastatic setting through to the adjuvant situation, there has been increased interest in the role of taxanes in neoadjuvant regimens. The use of taxane-based therapies in this setting has so far shown improvements over more standard regimens in terms of clinical response rates, breast conservation, pathologic response rates, disease free survival, and overall survival. The aim of this review is to systematically summarize and interpret the results of published randomized controlled trials of neoadjuvant taxane chemotherapy for women with non-metastatic breast cancer.

Breast Neoplasms↗

PubMed2001

Determination of regional ventilation and perfusion in the lung using xenon and computed tomography.

We propose a model to measure both regional ventilation (V) and perfusion (Q) in which the regional radiodensity (RD) in the lung during xenon (Xe) washin is a function of regional V (increasing RD) and Q (decreasing RD). We studied five anesthetized, paralyzed, mechanically ventilated, supine sheep. Four 2.5-mm-thick computed tomography (CT) images were simultaneously acquired immediately cephalad to the diaphragm at end inspiration for each breath during 3 min of Xe breathing. Observed changes in RD during Xe washin were used to determine regional V and Q. For 16 mm(3), Q displayed more variance than V: the coefficient of variance of Q (CV(Q)) = 1.58 +/- 0.23, the CV of V (CV(V)) = 0.46 +/- 0.07, and the ratio of CV(Q) to CV(V) = 3.5 +/- 1.1. CV(Q) (1.21 +/- 0.37) and the ratio of CV(Q) to CV(V) (2.4 +/- 1.2) were smaller at 1,000-mm(3) scale, but CV(V) (0.53 +/- 0.09) was not. V/Q distributions also displayed scale dependence: log SD of V and log SD of Q were 0.79 +/- 0.05 and 0.85 +/- 0.10 for 16-mm(3) and 0.69 +/- 0.20 and 0.67 +/- 0.10 for 1,000-mm(3) regions of lung, respectively. V and Q measurements made with CT and Xe also demonstrate vertically oriented and isogravitational heterogeneity, which are described using other methodologies. Sequential images acquired by CT during Xe breathing can be used to determine both regional V and Q noninvasively with high spatial resolution.

Algorithms↗

PubMed2001

Cost-Utility analysis of tissue plasminogen activator therapy for acute ischaemic stroke: a Canadian healthcare perspective.

BACKGROUND: There are over 40000 ischaemic strokes annually in Canada, which result in significant morbidity, mortality and burden to the healthcare system. A recent, large clinical trial has evaluated tissue plasminogen activator (t-PA) intravenously for the treatment of acute ischaemic stroke with promising outcomes but with an increased risk of symptomatic intracranial haemorrhage. OBJECTIVE: To compare clinical and economic outcomes of intravenous t-PA therapy (0.9 mg/kg, to a maximum of 90 mg, initiated within 3 hours of stroke onset) versus no t-PA for acute ischaemic stroke based on the outcomes achieved in the National Institute of Neurological Disorders and Stroke (NINDS) trial. DESIGN: A Markov model depicting the natural lifetime course after an initial acute ischaemic stroke. On the basis of this model, a simulated trial compared no t-PA with t-PA. PATIENTS: A hypothetical cohort of 1000 patients with acute ischaemic stroke. STUDY PERSPECTIVE: Canadian healthcare system. OUTCOME MEASURES: Total acute stroke and post-stroke treatment costs and cumulative quality-adjusted life-years (QALYs). RESULTS: For a hypothetical cohort of 1000 patients, the estimated lifetime stroke costs were 103100000 Canadian dollars (SCan) [1999 values) in the t-PA arm ($Can103100 per patient) compared with SCan106900000 in the no t-PA arm ($Can106900 per patient), yielding a lifetime cost difference of $Can3800000 in favour of t-PA versus no t-PA (SCan3800 per patient). In the hypothetical cohort, t-PA treatment resulted in 13 130 QALYs versus 9670 QALYs with no t-PA treatment. This translated into a net benefit of 3460 additional QALYs per 1000 patients (3.46 QALYs per patient). No treatment, outcome or economic variables influenced the model outcome. CONCLUSION: From the standpoint of cost effectiveness, treatment of acute ischaemic stroke with intravenous t-PA is an economically attractive strategy.

Canada↗

PubMed2000

Exercise alters fractal dimension and spatial correlation of pulmonary blood flow in the horse.

We determined the changes in fractal dimensions and spatial correlations of regional pulmonary blood flow with increasing exercise in race horses (n = 4) by using 15-microm fluorescent microspheres. Fluorescence was measured to quantitate regional blood to 1.3-cm(3) samples (n = 1,621-2,503). Perfusion distributions were characterized with fractal dimensions (a measure of spatial variability) and spatial correlations. On average, the fractal dimension decreased with exercise (trot 1.216 to gallop 1.173; P < 0. 05) despite a variable fractal dimension at rest. Spatial correlation of flow to neighboring pieces increased with exercise (trot 0.57 +/- 0.074 to gallop 0.73 +/- 0.051) and was inversely correlated with fractal dimension, indicating better spatial correlation as blood flow distribution becomes more uniform. This is the first study to document a change in fractal dimension as a result of increasing pulmonary blood flow. Spatial differences in response to vasoregulatory mediators may play a role in this phenomenon.

Algorithms↗

PubMed2000

Effects of inertial load and countermeasures on the distribution of pulmonary blood flow.

We assessed the influence of cranial-to-caudal inertial force (+G(z)) and the countermeasures of anti-G suit and positive pressure breathing during G (PBG), specifically during +G(z), on regional pulmonary blood flow distribution. Unanesthetized swine were exposed randomly to 0 G(z) (resting), +3 G(z), +6 G(z), and +9 G(z), with and without anti-G suit and PBG with the use of the Air Force Research Laboratory centrifuge at Brooks Air Force Base (the gravitational force of the Earth, that is, the dorsal-to-ventral inertial force, was present for all runs). Fluorescent microspheres were injected into the pulmonary vasculature as a marker of regional pulmonary blood flow. Lungs were excised, dried, and diced into approximately 2-cm(3) pieces, and the fluorescence of each piece was measured. As +G(z) was increased from 0 to +3 G(z), blood flow shifted from cranial and hilar regions toward caudal and peripheral regions of the lung. This redistribution shifted back toward cranial and hilar regions as anti-G suit inflation pressure increased at +6 and +9 G(z). Perfusion heterogeneity increased with +G(z) stress and decreased at the higher anti-G suit pressures. The distribution of pulmonary blood flow was not affected by PBG. ANOVA indicated anatomic structure as the major determinant of pulmonary blood flow.

Animals↗

PubMed1997