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Biomedical subjects

M Peacock

Publications and source records attributed to M Peacock.

At least 73 records · Page 4Linked to original sources

Geometric structure of the femoral neck measured using dual-energy x-ray absorptiometry.

An algorithm was developed to estimate the strength of the femoral neck from data generated by the dual-energy x-ray absorptiometry (DXA). This algorithm considers shape of the proximal femur as well as cross-sectional moment of inertia (CSMI) in the estimate. Proximal femora (10) from cadavers of white adults and an aluminum step wedge were scanned with the Lunar DPX to validate the calculation of CSMI. After scanning, each femoral neck was sectioned at its narrowest portion for direct measurement of CSMI. Three healthy young women were scanned five times each to evaluate the reproducibility of geometric measurements using DXA. There was a strong linear association between the CSMI measured directly and using DXA in both cadaver bones (r2 = 0.96) and the aluminum step wedge (r2 = 0.99). The coefficient of variation for CSMI from repeated measurements using DXA was less than 3%. This indicates that it is possible to estimate reproducibly the bending rigidity of bone from DXA measurements. The data from 306 normal subjects were analyzed to investigate geometric changes in the femoral neck with age. Although there was no strong correlation between CSMI and age in normal subjects of either sex, safety factor (SF, an index of strength of the femoral neck during walking) and fall index (FI, an index of the strength of the femoral neck during a fall) decrease with age in both sexes. We observed an alteration of the geometric structure of the femoral neck with age that may increase the stress on the femoral neck and decrease SF and FI.

Absorptiometry, Photon↗

Do variations in hip geometry explain differences in hip fracture risk between Japanese and white Americans?

Despite lower femoral neck bone mass, Japanese women have a substantially lower incidence of hip fracture than North American whites. Reasons for this discrepancy were sought in a study of 57 Japanese and 119 white American women aged 50-79. All women were in good health. Bone mineral content (BMC) in the femoral neck, femoral neck length (NL), femoral neck angle (theta), cross-sectional moment of inertia (CSMI), safety factor (SF), and fall index (FI) were calculated using dual x-ray absorptiometry. Height and weight were greater in Americans than in Japanese (1.62 versus 1.52 m; p < 0.0001 and 66.0 versus 49.4 kg; p < 0.0001, respectively). Mean BMC in the femoral neck and CSMI were greater in Americans than in Japanese (3.91 versus 3.02 g; p < 0.0001 and 0.99 versus 0.57 cm4; p < 0.0001, respectively). NL was longer in Americans (5.6 versus 4.4 cm; p < 0.0001) and theta was larger in Americans (130 versus 128 degrees; p < 0.01), whereas SF and FI were less in Americans than in Japanese (3.41 versus 5.12; p < 0.0001 and 1.00 versus 1.40; p < 0.0001, respectively). These results indicate that despite lower bone mass, Japanese women have lower risks of structural failure in the femoral neck, attributable primarily to shorter femoral necks and, to a lesser degree, a smaller femoral neck angle. Geometric characteristics of the femoral neck in Japanese women are associated with their lower hip fracture risk, and the measurement of proximal femoral geometry, combined with bone mass, may provide further clinical information about the risk of hip fracture.

Absorptiometry, Photon↗

Bone mineral density in relation to polymorphism at the vitamin D receptor gene locus.

Polymorphism at the vitamin D receptor gene was examined in relation to bone mineral density (BMD) at spine, femur, and forearm in 86 monozygotic (MZ) and 39 dizygotic (DZ) adult female twins. All were white, 63 pairs (44 MZ, 19 DZ) were premenopausal, and 43 pairs (31 MZ, 12 DZ) were discordant for age at menopause or use of estrogen. Each individual of the DZ pairs and one individual of MZ pairs was genotyped for ApaI, BsmI, and TaqI polymorphism at the vitamin D receptor gene locus using Southern hybridization. Intraclass correlations for BMD in MZ and DZ twin pairs indicated that heritability accounted for over 70% of BMD. There was no relationship between genotype for any of the three polymorphisms and BMD at any skeletal site in the twin population, considered either as a total population, both with and without twins discordant for age at menopause or use of estrogen, or as a premenopausal population. In DZ twin pairs discordant for alleles for the three polymorphisms, no allele was associated with higher or lower BMD. It is concluded that in this population of healthy adult females there was no relationship between these polymorphisms at the vitamin D receptor gene locus and BMD.

Adult↗

Red blood cell depletion and enrichment of CD34+ hematopoietic progenitor cells from human umbilical cord blood using soybean agglutinin and CD34 immunoselection.

Realization of the full potential of human umbilical cord blood (HUCB) as a source of transplantable hematopoietic progenitor cells (HPC) will be contingent on the development of a reliable method for ex vivo cell processing and stem cell enrichment. A first step in stem cell enrichment protocols involves depletion of the red blood cells (RBC) in the sample. We have compared several RBC depletion methods on the basis of recovery of total nucleated cells. It was found that 3% gelatin was effective at depleting RBC with a nucleated cell recovery of 72.4 +/- 7.3% (mean +/- standard deviation [SD]) in the HUCB samples. Several lectins were also used for processing HUCB and compared for their ability to remove RBC. Of these, soybean agglutinin (SBA) was found to remove RBC without substantial loss of HPC. Moreover, sequential treatment of HUCB with 3% gelatin and the AIS MicroCELLector SBA resulted in a product with < 1% hematocrit, 57% reduction in T cells, 35% nucleated cell recovery, and relatively high yields of burst-forming units-erythroid (BFU-E) (61%) and colony-forming units-granulocyte/macrophage (CFU-GM) (58%) and -mixed (CFU-GEMM) (66%). In a separate series of studies, enrichment of the CD34+ subset in HUCB was accomplished by processing HUCB with Ficoll followed by sequential treatment with the AIS MicroCELLector SBA and AIS MicroCELLector CD34. The CD34+ fraction was enriched for BFU-E (14-fold), CFU-GM (nine-fold), and CFU-GEMM (five-fold) with an overall purity ¿ > or = 92% CD34+ by flow cytometry. This report demonstrates that 3% gelatin and the AIS MicroCELLector SBA can be combined as an ex vivo processing technique to reduce the volume of the HUCB product by depleting RBC and T cells while still maintaining a high recovery of HPC. Moreover, separation of highly enriched CD34+ cells from HUCB is achievable and opens up the possibility of using CD34+ cells from HUCB for ex vivo progenitor cell expansion for transplantation, transfusion, and gene therapy.

Antigens, CD↗

Allocation of attention and task difficulty.

Individuals with and without mental retardation did a dual task procedure designed to investigate how task difficulty influenced the allocation of attention. The primary task required semantic category decisions. Subjects sorted cards according to whether the object pictured on the card belonged to a target category. The easy decision task used basic level categories (horse and hammer). The difficult decision task used superordinate categories (animals and tools). While making decisions, subjects were required to signal detection of auditory probes. Response times to the probes were used to index attention to the primary task. Subjects without mental retardation allocated more attention to the difficult task. Those with mental retardation gave similar attention to the easy and difficult tasks. Possible explanations for their failure to allocate attention in accordance with task difficulty were discussed.

Adolescent↗

Cytokine production and surface antigen expression by peripheral blood mononuclear cells in postmenopausal osteoporosis.

It was reported earlier that IL-1 production by cultured monocytes and the ratio of helper (CD4) to suppressor (CD8) lymphocytes in peripheral blood are different in osteoporotic compared to nonosteoporotic subjects. We examined these and several other parameters related to the biosynthetic activity and differentiation status of peripheral blood mononuclear cells (PBMC) in untreated osteoporotic postmenopausal women (age 65 +/- 7, n = 46), nonosteoporotic postmenopausal women (age 55 +/- 3, n = 20), and nonosteoporotic premenopausal women (age 37 +/- 7, n = 8), as defined by spine density. We found that unstimulated monocytes from osteoporotics did not produce detectable IL-1 beta as determined by ELISA. In addition, there were no significant differences between osteoporotics and nonosteoporotics in IL-1 beta or IFN-gamma production by PBMC stimulated with OKT3, a monoclonal antibody to the T cell-receptor complex. The proliferative response of lymphocytes to OKT3 was significantly less (p < 0.02) in osteoporotics compared to nonosteoporotic post- and premenopausal women; multiple-regression analysis, however, indicated that this difference was not due to bone density but to age. Flow cytometric analysis of PBMC revealed no difference between osteoporotics and nonosteoporotics in the distribution of 18 phenotypic subsets determined, including CD4- or CD8-positive lymphocytes or the ratio of CD4 to CD8 cells. Further, there was no correlation of the surface markers with bone density, the exceptions being the subsets expressing the CD3/CD56 and CD8/CD56 markers, which were inversely related to spine density in the osteoporotic women.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Separation of hematopoietic progenitor cells from human umbilical cord blood.

Human umbilical cord blood (HUCB) is a rich source of hematopoietic progenitor cells (HPC). Nevertheless, it has been previously reported that attempts to enrich for HPC resulted in substantial loss of progenitor cells. We have developed a cell processing technique for HUCB using 3% gelatin sedimentation and the AIS MicroCELLectorSBA and CD34. By this technique, we were able to deplete red blood cells (RBC) and obtain a partial T cell depletion, while maintaining 70-90% of the HPC. The results indicate that it may be possible to manipulate cord blood without significant loss of HPC, thus enhancing its utility for transplantation.

Antibodies, Monoclonal↗

Effect of recombinant human growth hormone on adreno-cortical function, and on sodium and potassium homeostasis.

In the present study we examined the effect of treatment with recombinant human growth hormone (rhGH) on adrenocortical secretory function, as well as sodium and potassium balance. rhGH, 100 micrograms/kg per day, was given for 4 days. Both glucocorticoid and androgen secretion were unaffected by treatment as evidence by unchanged levels of cortisol and dehydroepiandrosterone-sulfate. rhGH resulted in retention of sodium and potassium and a decrease in serum potassium concentration, but neither aldosterone plasma levels nor urinary excretion rates changed until after treatment. During the rhGH washout phase, a natriuresis ensued, but this occurred slowly possibly in part because a higher serum potassium stimulated aldosterone secretion. In summary, short-term treatment with rhGH had no immediate effect on adrenocortical function, but caused pronounced retention of electrolytes. In the posttreatment period, there were increases in aldosterone secretion accompanied by delayed recovery from the retention of sodium.

Adrenal Cortex↗

Calcium supplementation and increases in bone mineral density in children.

BACKGROUND: Increased dietary intake of calcium during childhood, usually as calcium in milk, is associated with increased bone mass in adulthood; the increase in mass is important in modifying the later risk of fracture. Whether the increase is due to the calcium content of milk, however, is not certain. METHODS: We conducted a three-year, double-blind, placebo-controlled trial of the effect of calcium supplementation (1000 mg of calcium citrate malate per day) on bone mineral density in 70 pairs of identical twins (mean [+/- SD] age, 10 +/- 2 years; range, 6 to 14). In each pair, one twin served as a control for the other; 45 pairs completed the study. Bone mineral density was measured by photon absorptiometry at two sites in the radius (at base line, six months, and one, two, and three years) and at three sites in the hip and in the spine (at base line and three years). RESULTS: The mean daily calcium intake of the twins given placebo was 908 mg, and that of the twins given calcium supplements was 1612 mg (894 mg from the diet and 718 mg from the supplement). Among the 22 twin pairs who were prepubertal throughout the study, the twins given supplements had significantly greater increases in bone mineral density at both radial sites (mean difference in the increase in bone mineral density: midshaft radius, 5.1 percent [95 percent confidence interval, 1.5 to 8.7 percent]; distal radius, 3.8 percent [95 percent confidence interval, 1.4 to 6.2 percent]) and in the lumbar spine (increase, 2.8 percent [95 percent confidence interval, 1.1 to 4.5 percent]) after three years; the differences in the increases at two of three femoral sites approached significance (Ward's triangle in the femoral neck, 2.9 percent; greater trochanter, 3.5 percent). Among the 23 pairs who went through puberty or were postpubertal, the twins given supplements received no benefit. CONCLUSIONS: In prepubertal children whose average dietary intake of calcium approximated the recommended dietary allowance, calcium supplementation increased the rate of increase in bone mineral density. If the gain persists, peak bone density should be increased and the risk of fracture reduced.

Absorptiometry, Photon↗

Interpretation of bone mass determinations as they relate to fracture: implications for asymptomatic primary hyperparathyroidism.

Determination of bone mass is currently the most clinically useful measurement of bone strength and of fracture risk. Interpretation of bone mass determination as it relates to fracture has been developed largely from studies of age-related bone loss. A decrease in bone mass and an increase in fracture incidence with aging are universal phenomena that are causally related by virtue of the major contribution bone mass makes to skeletal strength. Over 70% of the skeleton's strength to resist fracture resides in its mineral content in vitro. Clinically, the relationship between trauma and fracture is complex, and in the general population, fracture appears as a random event occurring more frequently as bone mass decreases. In the individual, measurement of bone mass in relation to the range of bone mass and the fracture incidence of the reference population provides an estimate of the risk of sustaining a fracture in the future. In primary hyperparathyroidism, interpretation of a bone mass determination must take into account the effect of the disease activity on the skeleton against the background of universal age-related changes in bone mass and fracture incidence. This general relationship is likely to be altered by at least three unique effects that parathyroid hormone may have on the skeleton: (1) parathyroid hormone has a differential effect on cortical and cancellous bone; (2) it has a biphasic effect on bone that is concentration dependent; and (3) it alters bone quality and architecture.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Calcium absorption efficiency and calcium requirements in children and adolescents.

Optimizing bone mass of young adults is important in the prevention of osteoporosis in later life. To achieve maximal peak bone mass, dietary calcium and its absorption need to be sufficient for skeletal growth and consolidation and for obligatory losses in urine, feces, and sweat. Direct measurements of skeletal accretion, obligatory losses, and of dietary calcium and absorption in children and adolescents have either not been done or are incomplete. From the measurements available and from extrapolated data in adults, it appears likely that many children and adolescents are not absorbing sufficient calcium in relation to their intake to achieve maximal bone mass.

Absorption↗

The architecture of cancellous and cortical bone in femoral neck fracture.

The architecture of cancellous bone as well as quantity and quality is considered important in maintaining mechanical integrity. To determine whether abnormalities of architecture occur in femoral neck fracture we measured trabecular width and number in iliac crest bone biopsies of 68 women with femoral fracture and compared them with data from a postmortem series of age-matched women without known bone disease. Cortical thickness was measured in 27 of the fracture patients and 17 controls. After exclusion of ten biopsies with increased osteoid surface no significant difference was seen in mean trabecular width or number between fracture patients and subjects without fracture. Both thinning of trabeculae and loss of trabeculae contributed to low bone volume in femoral fracture patients. Direct measurements of trabecular number correlated with calculated mean trabecular plate density (P less than 0.001), and the percentage of trabeculae at any one of a range of trabecular widths in the fracture biopsies was similar to that in non-fracture subjects. No difference was seen in the architecture of cancellous bone with age, fracture trauma or between subcapital and intertrochanteric fracture in fracture subjects. Cortical thickness, however, was related to age in both fracture and control subjects (P less than 0.05). There was no difference in cortical thickness between age-matched fracture and control subjects. Patients with intertrochanteric fracture had lower cortical thickness (P less than 0.02) and were older (P less than 0.01) than patients with subcapital fracture.

Aged↗

Osteomalacia and osteoporosis in femoral neck fracture.

Iliac crest bone histomorphometry, plasma and urine biochemistry and clinical history were examined in 78 unselected patients (68 women, 10 men) at the time of femoral fracture. Histological abnormalities occurred in 56 of the 78 biopsies. The commonest of these was a low bone volume of less than 15% which, irrespective of other abnormal histological features, was present in 37 of the biopsies. On the basis of the histomorphometry, patients could be classified into four main groups. Normal histomorphometry (bone volume greater than 15%, osteoid surfaces less than 24%, mineralising surface greater than 60%) was present in 22 patients, 23 had osteoporosis as the only abnormality (bone volume less than 15%, osteoid surface less than 24%, mineralising surface greater than 60%), nine had osteomalacia (osteoid surfaces greater than 24%, mineralising surface less than 60%, osteoid width greater than 13 microns) and 13 had decreased mineralising surfaces. Of the remainder, five had increased osteoid surface and six had insufficient osteoid to assess mineralising surface. Plasma and urine biochemistry in the four groups showed that, compared to age-matched controls, all groups had reduced plasma albumin. In comparison to the group with normal histomorphometry, patients with osteoporosis had a higher plasma calcium (P less than 0.01), tubular reabsorption of calcium (P less than 0.05) and plasma vitamin D binding protein (P less than 0.01); patients with osteomalacia had a higher plasma creatinine (P less than 0.02) and parathyroid hormone (P less than 0.02) and lower plasma 24,25-dihydroxyvitamin D (P less than 0.02), urinary calcium/creatinine ratio (P less than 0.02) and tubular reabsorption of phosphate (P less than 0.02). The biochemistry in patients with decreased mineralising surface was no different from patients with a normal biopsy. The prevalence of both osteoporosis and osteomalacia increased with age and, in subjects over the age of 90, osteoporosis occurred in 71% of patients and osteomalacia occurred in 29% of patients. The osteomalacic group were significantly older than the other three groups (P less than 0.05). The histomorphometry did not relate to the site of fracture (subcapital or intertrochanteric). A history of stroke, gastrectomy, rheumatoid arthritis, steroid treatment, thyroid disease, alcohol abuse and anti-convulsant therapy was present in patients with femoral fracture but did not relate to any particular histomorphometric classification.

Age Factors↗

Calcium absorption in children estimated from single and double stable calcium isotope techniques.

In order to determine whether the specific activity in a single serum sample estimates calcium absorption, six healthy children participated in a study using stable isotopic calcium tracers, one given orally and the second intravenously. High-resolution, fast atom bombardment mass spectrometry was used to quantify the 44Ca and 42Ca tracers in serum and urine. Subjects ingested 250 mg of calcium (215 mg calcium enriched with 35 mg 44Ca) in the form of a chewable calcium citrate malate tablet with a standard meal, followed 30 min later with an i.v. injection of 42Ca tracer. Blood for tracer determinations was obtained at 90, 120, 150, 180, and 300 min after oral ingestion, and a urine sample was obtained 24 h after oral calcium tracer administration. The average calcium absorption estimated from the ratio of urinary tracers was 41.4 +/- 8.2%. This study indicates that the level of oral tracer in serum taken 150 min post-ingestion is significantly correlated (r = 0.85, p less than 0.05) with calcium absorption, as determined by the tracer levels in the urine. These results show that an oral stable isotopic tracer coupled with a single blood sample can be used to estimate calcium absorption in children.

Absorption↗

Spinal osteoporosis in men.

In 94 men with crush fracture, 40 were found to have primary osteoporosis. Cross-sectional measurements of a number of variables related to bone in these 40 patients were compared to the values in various groups of healthy men aged 20-96. In healthy men, metacarpal and femoral cortical area/total area, bone volume, osteoid surfaces, seam and trabecular width, plasma dihydroepiandrosterone and estrone, and radiocalcium absorption fell with age, whereas eroded surfaces, trabecular number, urine hydroxyproline and calcium/creatinine ratios, plasma alkaline phosphatase, estradiol, androstenedione, cortisol and testosterone remained constant with age. As compared with healthy men, men with primary osteoporosis had reduced femoral cortical area/total area (P less than 0.05), and Singh grade (P less than 0.001) and in seven there was a history of forearm or femoral fracture. On iliac crest biopsy, bone volume (P less than 0.001) and trabecular number (P less than 0.01) were decreased. Plasma alkaline phosphatase (P less than 0.02) was increased but urine hydroxyproline and calcium excretion were not significantly raised. Calcium balance was negative due to failure of absorption to match urinary calcium loss and radiocalcium absorption (P less than 0.01) and plasma 1,25-dihydroxyvitamin D (P less than 0.05) were reduced.

Adult↗

Comparison of the effects of oral and transdermal oestradiol administration on oestrogen metabolism, protein synthesis, gonadotrophin release, bone turnover and climacteric symptoms in postmenopausal women.

We compared the effect of administering oestradiol via the transdermal or oral routes in six and eight postmenopausal women respectively. Although both treatments achieved similar plasma levels of oestradiol, oral administration led to much greater increases in plasma levels of oestrone and the sulphates and glucuronides of oestradiol, oestrone and oestriol than transdermal treatment (P less than 0.001). Both treatments reduced plasma FSH; from 42 +/- 10 (SE) IU/l to 30 +/- 2 IU/l with oral and from 46 +/- 7 IU/l to 28 +/- 6 IU/l with transdermal treatment. Urine calcium excretion fell from 0.41 +/- 0.06 (molar ratio to creatinine) to 0.17 +/- 0.02 with oral and from 0.25 +/- 0.06 to 0.13 +/- 0.02 with transdermal treatment. Patients' symptoms were improved by both treatments. These changes were related to the plasma oestradiol concentration but not to that of oestrone. Oral, but not transdermal, treatment stimulated hepatic protein synthesis as shown by increased plasma levels of both vitamin-D-binding globulin and sex-hormone-binding globulin. We conclude that although both oral and transdermal oestradiol reduce postmenopausal bone loss, gonadotrophin secretion and symptoms, oral treatment also leads to hepatic stimulation and extensive metabolism of oestradiol, both of which may increase side-effects without conferring additional benefit.

Administration, Oral↗