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Biomedical subjects

G Gamble

Publications and source records attributed to G Gamble.

50 records · Page 3Linked to original sources

Long-term stability studies on the WHO IRP for thromboplastin (human plain BCT/253).

Long-term stability studies on the WHO second primary International Reference Preparation (IRP) for thromboplastin (human plain BCT/253) stored at -20 degrees C have been conducted for ten years. Three centres took part in the exercise using frozen normal and coumarinised plasma samples which were tested throughout. There has been no measurable change in the prothrombin time performance of the human plain IRP over the ten-year period. It can therefore be concluded that new IRP may continue to be calibrated against this preparation in accord with WHO recommendations.

Analysis of Variance↗

B-mode ultrasound images of the carotid artery wall: correlation of ultrasound with histological measurements.

B-mode ultrasound is being used to assess carotid atherosclerosis in epidemiological studies and clinical trials. Recently the interpretation of measurements made from ultrasound images has been questioned. This study examines the anatomical correlates of B-mode ultrasound of carotid arteries in vitro and in situ in cadavers. Twenty-seven segments of human carotid artery were collected at autopsy, pressure perfusion fixed in buffered 2.5% glutaraldehyde and 4% paraformaldehyde and imaged using an ATL UM-8 (10 MHz single crystal mechanical probe). Each artery was then frozen, sectioned and stained with van Gieson or elastin van Gieson. The thickness of the intima, media and adventitia were measured to an accuracy of 0.01 mm from histological sections using a calibrated eye graticule on a light microscope. Shrinkage artifact induced by histological preparation was determined to be 7.8%. Digitised ultrasound images of the artery wall were analysed off-line. The distance from the leading edge of the first interface (LE1) to the leading edge of the second interface (LE2) was measured using a dedicated programme. LE1-LE2 measurements were correlated against histological measurements corrected for shrinkage. Mean values for the far wall were: ultrasound LE1-LE2 (0.97 mm, S.D. 0.26), total wall thickness (1.05 mm, S.D. 0.37), adventitia (0.35 mm, S.D. 0.16), media (0.61 mm, S.D. 0.18), intima (0.09 mm, S.D. 0.13). Ultrasound measurements corresponded best with total wall thickness, rather than elastin or the intima-media complex. Excision of part of the intima plus media or removal of the adventitia resulted in a corresponding decrease in the LE1-LE2 distance of the B-mode image. Furthermore, increased wall thickness due to intimal atherosclerotic thickening correlated well with LE1-LE2 distance of the B-mode images. B-mode images obtained from the carotid arteries in situ in four cadavers also corresponded best with total wall thickness measured from histological sections and not with the thickness of the intima plus media. In conclusion, the LE1-LE2 distance measured on B-mode images of the carotid artery best represents total wall thickness of intima plus media plus adventitia and not intima plus media alone.

Adult↗

Determinants of birth-weight in women with established and gestational diabetes.

Increased birth-weight (macrosomia) can complicate the diabetic pregnancy, but many factors other than hyperglycaemia can influence birth-weight, in particular maternal obesity. In a mixed population (European, Maori and Pacific Islander) with a high prevalence of glucose intolerance and obesity we have examined the relative impact of various maternal factors on birth-weight in women with both established and gestational diabetes. Mean birth-weight was significantly greater in women with established or gestational diabetes than in controls (p < 0.0001), but was similar in women with gestational and established diabetes, despite glycaemic control being significantly poorer (p < 0.0001) in the latter. Birth-weight closely paralleled prepregnancy body mass index rather than glycaemic control, but in Maori women it was lower than expected, probably because of their high prevalence of smoking. Daily cigarette consumption was negatively correlated with birth-weight (p < 0.01) despite the smokers having significantly poorer glycaemic control (p < 0.001). The most significant variables influencing birth-weight in the diabetic pregnancy were gestational age at delivery, prepregnancy body mass index, maternal height, estimated weight gain during pregnancy, the presence of hypertension and cigarette smoking (the latter 2 having negative effects on birth-weight). Glycaemic control in the last half of pregnancy was not significant in this analysis. We conclude that within the limits of glycaemic control which we obtained, birth-weight was largely determined by maternal factors other than hyperglycaemia. Birth-weight thus has severe limitations as an outcome measure of the diabetic pregnancy.

Adult↗

Molecular characterization of a large homozygous deletion in the small cell lung cancer cell line U2020: a strategy for cloning the putative tumor suppressor gene.

Homozygous deletions are instrumental in the detection and cloning of tumor suppressor genes. We report the isolation and characterization of 39 new single-copy probes saturating a submicroscopic homozygous deletion detected in the DNA of the small cell lung cancer (SCLC) cell line U2020. The probes were selected from a large collection, covering the entire length of chromosome 3 with an estimated average spacing of 100-150 kb. Based on the number of probes in the deletion and the probe density, the size of the U2020 submicroscopic deletion was estimated to be in the range of 4-7 megabases. Among the deleted loci, 17 showed conservation across species, probably representing potential coding gene sequences. By genetic and physical mapping of a large randomly chosen fraction of the deleted probes, we defined the location of the U2020 deletion within chromosome band 3p12. Our cloning strategy is based on narrowing the region of interest by eliminating probes that retain heterozygosity in SCLC samples, thus selecting for probes in the region of common loss.

Blotting, Southern↗

Determinants of total body and regional bone mineral density in normal postmenopausal women--a key role for fat mass.

In order to determine which clinical, anthropometric, dietary, and biochemical variables are independent predictors of total and regional bone mineral density (BMD) in normal postmenopausal women, a cross-sectional study of 140 normal postmenopausal women has been carried out. Subjects were white, aged 45-71 yr (mean 58 yr), and had no history of disorders or medication use likely to influence bone or calcium metabolism. Multiple regression analysis was used to derive models for total and regional BMD in terms of the other variables measured. The analysis indicated that total body BMD was positively related to fat mass (P less than 0.0001), serum estrone (P = 0.0095) and age at menopause (P = 0.0165), and negatively related to age (P less than 0.0001), 24-h urine calcium (P = 0.0002), sex hormone-binding globulin (P = 0.0003), and serum alkaline phosphatase activity (P = 0.0029) (R2 = 0.61). Similar relationships were found in the subregions of the total body scans and in the lumbar spine and proximal femur, with insulin-like growth factor-1, parity, and age at menarche also being related to BMD at at least two of these sites. Lean body mass was not an independent correlate of BMD at any site once fat mass was taken into account. Muscle strength, physical activity, alcohol intake, and dietary intakes of calcium, sodium and protein did not emerge as significant predictors of BMD in this homogeneous group of postmenopausal women. We conclude that total body fat is the most significant predictor of BMD throughout the skeleton and this relationship is not explicable in terms of either estrone production in fat tissue or the dependence of skeletal load-bearing on fat mass. The mechanism underlying this relationship is an important question to be addressed in bone biology.

Aged↗

Early prevention of left ventricular dysfunction after myocardial infarction with angiotensin-converting-enzyme inhibition.

Left ventricular dysfunction can be improved with angiotensin-converting-enzyme inhibition started 1 week after myocardial infarction or later. To see whether earlier intervention may confer greater benefit, a double-blind study was carried out in which 100 patients with Q wave myocardial infarction, but without clinical heart failure, were randomly allocated treatment with captopril 50 mg twice daily or placebo starting 24-48 h after onset of symptoms. Left ventricular volumes were measured regularly during 3 months of treatment and after a 48 h withdrawal period by means of two-dimensional echocardiography. The placebo group showed significant increases in left ventricular end-diastolic (LVEDVI) and end-systolic (LVESVI) volume indices, with the ejection fraction unchanged. By contrast, the captopril group showed a slight but not significant rise in LVEDVI and a significant reduction in LVESVI with ejection fraction increased significantly. At 3 months there was a 4.6% difference in the change in ejection fraction from baseline between the groups (p less than 0.0001). Most of the treatment benefit was evident at 1 month and there were no changes in left ventricular volumes after 48 h withdrawal of treatment at 3 months. Heart failure requiring treatment with frusemide developed in 7 patients in each group during the study period; 3 of these (1 captopril-treated, 2 placebo-treated) had to be withdrawn from the trial with severe heart failure requiring open treatment. Thus early treatment with captopril is effective in preventing the ventricular dilatation that can occur after Q wave myocardial infarction.

Angiotensin-Converting Enzyme Inhibitors↗

The acromegalic rosary.

Palpable enlargement of the costochondral junctions on the anterolateral chest wall was detected in 26 of 27 patients with acromegaly. In a further study three doctors wearing eyemasks examined a further 13 acromegalic patients and 12 control subjects; costochondral enlargement was detected with a sensitivity of 77% and specificity of 86%. It was not found in normal subjects in the absence of previous chest injury. The presence and extent of costochondral enlargement was unrelated to the duration of active or cured acromegaly, the initial or present growth hormone concentrations, or other clinical features of growth hormone excess. Costochondral enlargement is a common clinical sign in acromegaly and can serve as a biological marker of previous or current growth hormone excess.

Acromegaly↗

Echocardiographic prediction of left ventricular volume after myocardial infarction.

Left ventricular volume is a strong determinant of survival after acute myocardial infarction. The aim of this study was to determine which clinical and echocardiographic criteria assessed early after myocardial infarction would predict later left ventricular dilation. Forty-eight patients with uncomplicated transmural myocardial infarction had echocardiography 5 to 10 days after myocardial infarction and assessment of clinical variables including peak creatine kinase and sum of electrocardiographic ST segment elevation. Left ventricular dimensions were measured from the echocardiogram in the parasternal view and also in the apical four and two chamber views at the level of the mitral leaflets, papillary muscles and apex. A cardiac wall motion score was obtained by segmental analysis of the apical views. Echocardiographic left ventricular volume was measured after 1 year from the apical views with use of a Simpson's rule method. Initial clinical and echocardiographic variables were correlated with the left ventricular volume at 1 year. There was a significant relation between the initial four and two chamber end-diastolic dimensions and the left ventricular volume at 1 year, particularly for dimensions measured at the apical level (four chamber R2 = 0.66, p = 0.0001, two chamber R2 = 0.61, p = 0.0001). Other clinical variables, parasternal left ventricular dimensions and cardiac wall motion score were not significantly related to left ventricular volume. A powerful three variable model obtained by multiple regression and including the initial two chamber apical dimension, cardiac wall motion score and body surface area accounted for 82% of the variation in left ventricular volume at 1 year.

Cardiac Volume↗

Validity and reproducibility of color enhancement of B-mode ultrasound images of far wall thickness of the common carotid artery.

Ultrasound measurement of wall thickness of the carotid artery is used in large cardiovascular clinical trials and epidemiologic studies. Improvements in measurement reproducibility could have important implications for study design and sample size calculations. This study examined the effects of B-mode color on the validity and reproducibility of measurements of far wall thickness of the common carotid artery. Six color maps were compared with normal and inverted gray scales. The validity of B-mode color was assessed by comparing histologic measurements from 20 excised human common carotid arteries with measurements made using each map. No differences were noted in the average far wall thickness measured by any method (all p > 0.99). The reproducibility of duplicate measurements was assessed using each of the B-mode color maps. The coefficient of variation between the two measurements ranged from 6.7% to 9.7%. These variations were not significantly different between each map or gray scale (p > 0.24). In conclusion, B-mode color maps do not distort ultrasound measurements of far wall thickness of the common carotid artery. The reproducibility of these measurements is neither significantly nor usefully improved by using different color maps. Because no additional information is obtained, the use of color may not be warranted.

Adult↗