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Biomedical subjects

M Peacock

Publications and source records attributed to M Peacock.

At least 37 records · Page 2Linked to original sources
PubMed2000

Videoscopic lung volume reduction surgery in an Australian public teaching hospital.

BACKGROUND: Lung volume reduction surgery (LVRS) has been a frequent literature topic in emphysema management recently. Opinions differ in regard to usefulness, efficacy, and selection criteria. AIMS: To present the results of our first 55 bilateral videoscopically resected group, with follow-up of up to three years, and to present some of the local methodology problems faced. METHODS: Thirty-nine men and 16 women, age range 40-77, had either upper lobe (42), mixed (two), or lower lobe (11) resections without buttressing (except for unilateral buttressing in several of the latter patients as part of an intrapatient comparison trial) according to their pattern of emphysema determined by CT and perfusion scanning. RESULTS: Thirty day mortality was 5.5%. Follow-up pulmonary function is available for 44 patients, and demonstrates a mean 51% improvement in FEV1, and significant improvement in FVC, PaO2, dyspnoea indices and walking distance, with a reduction in mean RV, TLC, PaCO2. FEV1 improvement is maintained above baseline at three years. Lower lobe surgery outcomes are at least as good as their upper lobe counterparts. CONCLUSIONS: Outcomes confirm improvements reported elsewhere, and suggest that videoscopic resection may provide worthwhile benefit to lower lobe patterns of emphysema. Other managment issues are discussed.

Activities of Daily Living↗
PubMed2000

Changes in calcium kinetics in adolescent girls induced by high calcium intake.

To identify the mechanism/s whereby calcium retention is increased by calcium intake in adolescent girls, kinetic studies were performed using stable calcium isotope tracers. Girls (n = 10; 12 +/- 1 yr old, mean +/- SD) were studied while on a controlled diet containing a low (21.2 mmol/day) and a high (47.4 mmol/day) calcium intake, in randomized order, using a cross-over design. Studies were separated by 1 month. Calcium tracers were administered after 1 week on the study diet, orally and iv; and serum, urine, and feces were collected for the following 14 days. Tracers were measured using fast atom bombardment mass spectrometry, and kinetic data were analyzed by compartmental modeling. Biochemical markers of bone turnover were measured in serum and urine samples. On high (compared with low) calcium intake, fractional absorption did not differ, absorbed calcium increased (19.6 +/- 7.5 vs. 8.0 +/- 2.5 mmol/day, mean +/- SD, P: < 0.001), calcium excreted in urine increased (2.8 +/- 1.7 vs. 2.1 +/- 1.1 mmol/day, P: < 0.01), calcium retained in bone increased (14.5 +/- 8.9 vs. 3.2 +/- 3.6 mmol/day, P: < 0.001), bone formation did not change, and bone resorption decreased by 32%. These changes, measured by kinetics, were corroborated by changes in markers of bone turnover. We conclude that increased bone retention of calcium, with high calcium intake in adolescent girls, is attributable to an increase in absorption and a decrease in bone resorption.

Adolescent↗
PubMed2000

Genome screen for QTLs contributing to normal variation in bone mineral density and osteoporosis.

A major determinant of the risk for osteoporosis is peak bone mineral density (BMD), which is largely determined by genetic factors. We recently reported linkage of peak BMD in a large sample of healthy sister pairs to chromosome 11q12-13. To identify additional loci underlying normal variations in peak BMD, we conducted an autosomal genome screen in 429 Caucasian sister pairs. Multipoint LOD scores were computed for BMD at four skeletal sites. Chromosomal regions with LOD scores above 1.85 were further pursued in an expanded sample of 595 sister pairs (464 Caucasians and 131 African-Americans). The highest LOD score attained in the expanded sample was 3.86 at chromosome 1q21-23 with lumbar spine BMD. Chromosome 5q33-35 gave a LOD score of 2.23 with femoral neck BMD. At chromosome 6p11-12, the 464 Caucasian pairs achieved a LOD score of 2.13 with lumbar spine BMD. Markers within the 11q12-13 region continued to support linkage to femoral neck BMD, although the peak LOD score was decreased to 2.16 in the sample of 595 sibling pairs. Our study is the largest genome screen to date for genes underlying variations in peak BMD and represents an important step toward identifying genes contributing to osteoporosis in the general population.

Adult↗
PubMed2000

Effect of calcium or 25OH vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60.

Dietary supplements that prevent bone loss at the hip and that can be applied safely in the elderly are likely to reduce hip fractures. A daily dietary supplement of 750 mg calcium or 15 microg 25OH vitamin D3 on bone loss at the hip and other sites, bone turnover and calcium-regulating hormones were studied over 4 yr in elderly volunteers using a randomized, double-blind, placebo-controlled trial. Bone mineral density (BMD) was measured by dual x-ray absorptiometry and bone structure by radiographs. Calcium biochemistry and bone turnover markers were measured in blood and urine. The 316 women entering the trial had a mean age of 73.7 yr and the 122 men of 75.9 yr. Baseline median calcium intake was 546 mg/day, and median serum 25OH vitamin D3 was 59 nmol/L. On placebo, loss of BMD at total hip was 2% and femoral medulla expansion was 3% over 4 yr. Calcium reduced bone loss, secondary hyperparathyroidism, and bone turnover. 25OH vitamin D3 was intermediate between placebo and calcium. Fracture rates and drop-out rates were similar among groups, and there were no serious adverse events with either supplement. A calcium supplement of 750 mg/day prevents loss of BMD, reduces femoral medullary expansion, secondary hyperparathyroidism, and high bone turnover. A supplement of 15 microg/day 25OH vitamin D3 is less effective, and because its effects are seen only at low calcium intakes, suggests that its beneficial effect is to reverse calcium insufficiency.

Aged↗
PubMed1999

Rates of growth and loss of bone mineral in the spine and femoral neck in white females.

This study characterizes the rates of growth and loss of bone mass as a function of age in white females. It combines longitudinal data from several studies of bone mass on healthy white female subjects ranging from age 6 to 90 years. Rates of change in bone area, bone mineral content (BMC) and bone mineral density (BMD) are estimated separately for the spine and the femoral neck of each individual using linear regression. The individual rates of change are then fitted as a nonparametric function of age using weighted moving averages, resulting in a curve of age-specific mean change as a function of age. When the curves of BMD were compared between the hip and the femoral neck, the cessation of bone growth and the onset of bone loss were found to occur at an earlier age at the hip than at the spine. No significant differences in the ages of maximum rates of growth or maximum loss were found between the two skeletal sites. This information will be useful for designing interventions to promote bone growth or retard bone loss.

Adolescent↗
PubMed1999

Polymorphism at an Sp1 binding site of COL1A1 and bone mineral density in premenopausal female twins and elderly fracture patients.

Polymorphism at an Sp1 binding site in the COL1A1 gene has been reported to be associated with bone mineral density (BMD) and osteoporotic vertebral fracture. We therefore examined for associations and linkage of the Sp1 polymorphism in the COL1A1 gene and BMD at the lumbar spine and femoral neck in 38 monozygotic (MZ) and 40 dizygotic (DZ) twin pairs of white adult women. All twins were premenopausal with an age range of 21-49 years. Sp1 genotypes of 56 patients with idiopathic osteoporotic vertebral fracture were examined for a preponderance of either genotype relative to our normal healthy twin subjects. In the twin sample no significant association was found between Sp1 genotypes and BMD at the spine and femoral neck. No linkage of Sp1 genotype and BMD at the spine or femoral neck was observed in DZ twins discordant for genotype. Frequencies of Sp1 genotypes were similar in our healthy (twin) and fracture population samples. In conclusion, in our American sample of premenopausal twins we found no association or linkage of the Sp1 polymorphism at the COL1A1 gene and BMD at the lumbar spine and femoral neck, and no over-representation of any Sp1 genotype was observed in our sample of patients with osteoporotic vertebral fracture. Taken together these results indicate that the Sp1 polymorphism is not related to BMD in our American sample, and contrasts with the findings in a British population.

Adult↗
PubMed1999

Bordetella pertussis waaA encodes a monofunctional 2-keto-3-deoxy-D-manno-octulosonic acid transferase that can complement an Escherichia coli waaA mutation.

Bordetella pertussis lipopolysaccharide (LPS) contains a single 2-keto-3-deoxy-D-manno-octulosonic acid (Kdo) residue, whereas LPS from Escherichia coli contains at least two. Here we report that B. pertussis waaA encodes an enzyme capable of transferring only a single Kdo during the biosynthesis of LPS and that this activity is sufficient to complement an E. coli waaA mutation.

Bordetella pertussis↗
PubMed1999

Sibling pair linkage and association studies between bone mineral density and the insulin-like growth factor I gene locus.

A major determinant of the risk for osteoporosis in later life is bone mineral density (BMD) attained during early adulthood. BMD is a complex trait that presumably is influenced by multiple genes. Insulin-like growth factor I (IGF-I) is an attractive candidate gene for osteoporosis susceptibility, because IGF-I has marked effects on bone cells and has been implicated in the pathogenesis of osteoporosis. The IGF-I gene contains a microsatellite repeat polymorphism approximately 1 kb upstream from the IGF-I gene transcription start site, and previous investigators have found a higher prevalence of the 192/192 genotype of this polymorphism among men with idiopathic osteoporosis compared to controls. In this study we used this IGF-I polymorphism to test for an association between this polymorphism and BMD in our large population of premenopausal women (1 sister randomly chosen from 292 Caucasian and 71 African-American families). We also used this polymorphism to detect linkage to BMD elsewhere in the IGF-I gene or in a nearby gene using sibling pair linkage analysis in healthy premenopausal sister pairs (542 sibling pairs: 418 Caucasian and 124 African-American). Neither test provided any evidence of linkage or association between the IGF-I gene locus and spine or femoral neck BMD in Caucasians or African-Americans.

Adult↗
PubMed1998

Bone mass and structure at the hip in men and women over the age of 60 years.

Bone mass and structure at the proximal femur are important predictors of hip fracture. The aims of this study were to compare in a large sample of elderly men and women the precision of measurements of bone mass and structure at multiple sites at the proximal femur, to examine their interrelationships, to establish their relationships with age and body size, and to examine criteria for defining geometric and architectural variables in bone structure. Women (n = 336) and men (n = 141) over the age of 60 years were studied cross-sectionally. Bone mineral density (BMD) and content (BMC) at the proximal femur were measured in duplicate by dual-energy X-ray absorptiometry (DXA). Shaft and total upper femur (hip) sites in addition to femoral neck, Ward's triangle and trochanter were measured. Structural variables, measured from radiographs and from DXA images, including cortical thickness at calcar femorale, lateral cotex and midfemur, width of the femur and medulla, Singh grade, hip and femoral axis length, femoral head and neck width and the center of mass of the femoral neck. BMD and BMC had high reproducibility and there were significant differences in reproducibility across sites. Among sites, total upper femur and shaft had the highest reproducibility. Duplicate measurements substantially improved reliability of the measurement and are recommended when the value is close to a diagnostic level or when it will be used to establish rates of change. Reproducibility of structural variables was also high except for the lateral cortex, center of mass and Singh grade. Variance due to measurement error did not change with either age or gender. Women were significantly different from men, after controlling for differences in body size, in all variables except Singh grade and medulla width. BMD and BMC were negatively related to age and positively to body size. Structural variables examined in relation to age and body size fell into two categories. The first comprised variables that were not age-related but were body-size-related suggesting that they could be classified as geometric variables. The second comprised variables that were both body-size-related and age-related, suggesting that they could be classified as architectural variables. Using these criteria, calcar and lateral cortex were architectural variables, whereas shaft width, hip and femoral axis length, femoral head and neck width, and center of mass were geometric in both men and women. In women, shaft cortex width and medulla width were age-related, whereas in men they were not. Singh grade showed no consistent pattern with age or body size in women and men.

Absorptiometry, Photon↗
PubMed1998

Age-related changes in serum undercarboxylated osteocalcin and its relationships with bone density, bone quality, and hip fracture.

The effect of the degree of carboxylation of osteocalcin (OC) on the properties of bone is unclear. The aim of this study was to relate serum concentrations of total OC (tOC) and undercarboxylated OC (ucOC), measured with a two-site immunoassay, to bone mineral density (BMD) at the femoral neck and ultrasonic transmitted velocity (UTV) at the os calcis in 257 women aged 60-99 years, 22 of whom had sustained a hip fracture. There was an increase in tOC (r = 0.19, P = 0.003) and ucOC (r = 0.20, P = 0.002) with age. No significant difference in tOC or ucOC between subjects with and without hip fracture was found. Serum tOC was negatively correlated with femoral neck BMD (r = -0.23, P = 0.0001) and os calcis UTV (r = -0.29, P = 0.0001) and partial correlations indicated that these relationships were independent of age. Serum ucOC also correlated negatively with os calcis UTV (r = -0.21, P = 0.001) and less strongly with femoral neck BMD (r = -0.13, P = 0.052). After adjusting for age, only the relationship between ucOC and os calcis UTV remained significant (r = -0.16, P = 0.017). It is concluded that in women over 60 years, the increase in tOC reflects an age-related rise in bone remodeling, whereas the increase in ucOC reflects an age-related fall in vitamin K status. The stronger relationship of ucOC with UTV than BMD suggests that the rise in ucOC may perhaps relate more to changes in bone quality than mineral content. Higher serum ucOC concentrations in subjects with a history of hip fracture could not be confirmed.

Age Factors↗
PubMed1998

Safety and efficacy of pulse and daily calcitriol in patients on CAPD: a randomized trial.

BACKGROUND: Calcitriol therapy is the mainstay of therapy for the treatment of secondary hyperparathyroidism. Oral administration of calcitriol is necessary in CAPD patients, but no studies have directly compared different routes of administration in this patient population. METHODS: To determine if the peak serum calcitriol level (pulse therapy) is more important than the total delivered dose, we randomized CAPD patients with mild to moderate secondary hyperparathyroidism to receive either pulse (3.0 microg twice a week, n = 10) or daily (0.75 microg a day, n = 8) oral calcitriol in comparable weekly doses. The main comparison was the rate of decline of serum intact parathyroid hormone (PTH) levels to reach the desired end-point of 100 pg/ml. The patients were dialysed with low-calcium dialysate and received only calcium-containing phosphate binders. RESULTS: Pharmacokinetic analysis after a single dose of 3.0 microg (pulse) vs 0.75 microg (daily) revealed 1,25(OH)2-vitamin D levels to be higher in the pulse group at 3 and 6 h, but equivalent by 12 h. The area under the curve for 1 week of daily and 1 week of pulse therapy was equal. The patients in the 2 arms had equivalent basal serum levels of PTH (pulse = 562 +/- 291 vs daily = 454 +/- 113 pg/ml), calcium (pulse = 2.32 +/- 0.20 vs daily = 2.32 +/- 0.12 mmol/l) and phosphorus (pulse = 1.32 +/- 0.52 vs daily = 1.35 +/- 0.26 mmol/l). The time required for the PTH to decrease to 100 pg/ml and the rate of decline in PTH were similar (time: pulse = 14.2 +/- 6.8 weeks, daily = 12.2 +/- 7 weeks; rate: pulse = 7.4 +/- 4.2 vs daily = 8.4 +/- 4.2% PTH/week; P = NS). The serum calcium increased similarly in both groups. Hypercalcaemia (> 2.9 mmol/l) was rare (pulse = 3, daily = 2 episodes). CONCLUSIONS: This study demonstrates that pulse and daily calcitriol are similarly effective and safe for the treatment of mild to moderate secondary hyperparathyroidism in CAPD patients despite higher peak levels of 1,25(OH)2-vitamin D with pulse therapy.

Adult↗
PubMed1998

Linkage of a QTL contributing to normal variation in bone mineral density to chromosome 11q12-13.

Osteoporosis is a leading public health problem that is responsible for substantial morbidity and mortality. A major determinant of the risk for osteoporosis in later life is bone mineral density (BMD) attained during early adulthood. BMD is a complex trait that presumably is influenced by multiple genes. Recent linkage of three Mendelian BMD-related phenotypes, autosomal dominant high bone mass, autosomal recessive osteoporosis-pseudoglioma, and autosomal recessive osteopetrosis to chromosome 11q12-13 led us to evaluate this region to determine if the underlying gene(s) could also contribute to variation in BMD in the normal population. We performed a linkage study in a sample of 835 premenopausal Caucasian and African-American sisters to identify genes underlying BMD variation. A maximum multipoint LOD score of 3.50 with femoral neck BMD was obtained near the marker D11S987, in the same chromosomal region as the three Mendelian traits mentioned above. Our results suggest that the gene(s) underlying these Mendelian phenotypes also play a role in determining peak BMD in the normal population and are the first using linkage methods to establish a chromosomal location for a gene important in determining peak BMD. These findings support the hypothesis that a gene responsible for one or more of the rare Mendelian BMD traits linked to chromosome 11q12-13 has an important role in osteoporosis in the general population.

Adult↗
PubMed1997

Sex steroids and bone mass in older men. Positive associations with serum estrogens and negative associations with androgens.

The purpose of this study was to determine whether bone density in older men was associated with serum sex steroids or sex hormone binding globulin (SHBG). Bone density and sex steroids were measured in men over age 65 at 6-mo intervals for an average of 2.1 yr. Bone density was significantly positively associated with greater serum E2 concentrations (+0.21 < r < +0.35; 0.01 < P < 0.05) at all skeletal sites. There were weak negative correlations between serum testosterone and bone density (-0.20 < r < -0.28; 0.03 < P < 0.10) at the spine and hip. SHBG was negatively associated only with bone density in the greater trochanter (r = -0.26, P < 0.05). Greater body weight was associated with lower serum testosterone and SHBG, and greater E2. Because of these associations, regression models which adjusted for age, body weight, and serum sex steroids were constructed; these accounted for 10-30% of the variability in bone density, and showed consistent, significant positive associations between bone density and serum E2 concentrations in men, even after adjustments for weight and SHBG. These data suggest that estrogens may play an important role in the development or maintenance of the male skeleton, much as is the case for the female skeleton. These data also indicate that, within the normal range, lower serum testosterone concentrations are not associated with low bone density in men.

Aged↗
PubMed1997

Effect of osteoarthritis in the lumbar spine and hip on bone mineral density and diagnosis of osteoporosis in elderly men and women.

To determine in the elderly the effect of osteoarthritis on bone mineral density (BMD) and on diagnosis of osteoporosis, lumbar spine and hip were radiographed and BMD measured by dual-energy X-ray absorptiometry (DXA) in 120 men and 314 women, aged 60-99 years. Prevalence and severity of osteoarthritis were scored on osteophytes, joint space narrowing and bone sclerosis. Ultrasound measurements were also made at the heel to examine whether osteoarthritis at hip or lumbar spine influence bone at this remote site. Osteophytes were the commonest feature, with men having a higher prevalence than women, and lumbar spine having more disease than hip. Lumbar spine osteophytes affected 75% of men and 61.1% of women, and hip osteophytes affected 31.7% of men and 27.4% of women. Stepwise multiple regression analysis using age, weight, height, osteophytes, sclerosis and joint space narrowing indicated that lumbar osteophytes explained 16.6% of variation in lumbar spine BMD in women, and 22.4% in men. Hip osteophytes had a minimal effect on hip BMD, accounting for only 2.2% of variation in women, and none in men. Sclerosis and joint narrowing had little effect on BMD at lumbar spine or hip. Indirect effects of osteoarthritis on BMD were small and inconsistent across genders. Lumbar spine osteophytes in men explained 3.1% of hip BMD variation and 6% of variation in speed of sound at the heel, whereas hip osteophytes in women explained 2.2% of lumbar spine BMD variation. Osteoporosis at the hip, defined as BMD < 2.5 SD of the young normal mean, was present in 33.1% of women and 25.8% of men, whereas, at the lumbar spine it was present in only 24.2% of women and 4.2% of men. However, in women and men free of spinal osteoarthritis, 37.7% of women and 10% of men had osteoporosis. We conclude that lumbar spine osteophytes affect most subjects over the age of 60 years, and contribute substantially to lumbar spine BMD measured in the anteroposterior position by DXA. The effect is largely direct by virtue of osteophytes being included in the BMD measurement. However, a small indirect effect on remote skeletal sites is also present. Diagnosis of osteoporosis and assessment of osteoporotic fracture risk in the elderly should be based on hip BMD and not on anteroposterior lumbar spine, unless spinal osteoarthritis has been excluded.

Aged↗
PubMed1997

Fluoride treatment increased serum IGF-1, bone turnover, and bone mass, but not bone strength, in rabbits.

We hypothesized that fluoride partly acts by changing the levels of circulating calcium-regulating hormones and skeletal growth factors. The effects of oral fluoride on 24 female, Dutch-Belted, young adult rabbits were studied. The rabbits were divided into two study groups, one control and the other receiving about 16 mg fluoride/rabbit/day in their drinking water. After 6 months of fluoride dosing, all rabbits were euthanized and bone and blood samples were taken for analyses. Fluoride treatment increased serum and bone fluoride levels by over an order of magnitude (P < 0.001), but did not affect body weight or the following serum biochemical variables: urea, creatinine, phosphorus, total protein, albumin, bilirubin, SGOT, or total alkaline phosphatase. No skeletal fluorosis or osteomalacia was observed histologically, nor did fluoride affect serum PTH or Vitamin D metabolites (P > 0.4). BAP was increased 37% (P < 0.05) by fluoride; serum TRAP was increased 42% (P < 0.05); serum IGF-1 was increased 40% (P < 0.05). Fluoride increased the vertebral BV/TV by 35% (P < 0.05) and tibial ash weight by 10% (P < 0.05). However, the increases in bone mass and bone formation were not reflected in improved bone strength. Fluoride decreased bone strength by about 19% in the L5 vertebra (P < 0.01) and 25% in the femoral neck (P < 0. 05). X-ray diffraction showed altered mineral crystal thickness in fluoride-treated bones (P < 0.001), and there was a negative association between crystal width and fracture stress of the femur (P < 0.02). In conclusion, fluoride's effects on bone mass and bone turnover were not mediated by PTH. IGF-1 was increased by fluoride and was associated with increased bone turnover, but was not correlated with bone formation markers. High-dose fluoride treatment did not improve, but decreased, bone strength in rabbits, even in the absence of impaired mineralization.

Acid Phosphatase↗
PubMed1997

Effects of nitric oxide synthase inhibitors on bone formation in rats.

NO is synthesized from L-arginine by at least three isoforms of nitric oxide synthase (NOS) and is known to function as a vasodilator and neurotransmitter. NO is produced by bone cells but its function in bone biology is, as yet, unclear. We hypothesized that NOS mediates bone formation in remodeling regions of the skeleton. We studied the effects of two NOS inhibitors: N(G)-nitro-L-arginine methyl ester (L-NAME), which is a general inhibitor of NOS activity and is known to inhibit the vasodilatory effects of the endothelial NOS (eNOS) isoform; and aminoguanidine, which is a selective inhibitor of the inducible NOS (iNOS) isoform. Our hypothesis was tested by treating rats with NOS inhibitors and measuring bone formation rates in the tibial epiphysis and diaphysis. Bone formation indices were measured using standard bone histomorphometry. L-NAME treatment significantly raised mean arterial blood pressure (MAP). This effect was partially reversed by addition of L-arginine. Aminoguanidine had no significant effect on MAP, indicating that it did not block eNOS. The treatments also had substantial effects on bone formation in remodeling trabecular bone. L-NAME did not significantly change trabecular bone formation rate, whereas aminoguanidine reduced bone formation rate in the tibial epiphysis by 79% compared with control. This reduction was completely reversed by L-arginine, suggesting that bone formation during remodeling is, in part, mediated through L-arginine metabolism. No effect of aminoguanidine on bone formation was seen in the tibial diaphysis, a site that undergoes minimal bone remodeling. This finding suggests that the L-arginine-NO pathway is important in bone remodeling.

Animals↗