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Biomedical subjects

R H Fleming

Publications and source records attributed to R H Fleming.

At least 19 recordsLinked to original sources
PubMed2006

Relationships between genetic, environmental and nutritional factors influencing osteoporosis in laying hens.

1. The effects upon bone quality of feeding limestone in flour or particulate form and housing type (cage or aviary) in lines of hens divergently selected for high (H) or low (L) bone strength over 7 generations were investigated. 2. As in previous generations, highly significant phenotypic differences between lines were observed in all measured bone traits at peak egg production (25 weeks) and towards the end of production (56 weeks) in both cage and aviary systems. 3. At 25 weeks there were no significant effects on bone variables of feeding particulate limestone although a significant reduction in osteoclast number was observed at this age. By 56 weeks osteoclast numbers were further reduced in hens fed particulate limestone and beneficial effects on some bone variables were observed in this treatment group. 4. The genotypic and dietary improvements upon bone quality were independent and additive at both ages. There were very few interactive effects. 5. Hens with the freedom to move in an aviary environment during the laying period had improved bone status compared to caged siblings. Environmental and genotypic effects were additive. 6. There were no effects of line on egg production although H line hens had slightly higher egg production by 56 weeks. Egg numbers were unaffected by diet. Eggshell thickness and strength were unaffected by line but hens fed particulate limestone had thicker- and stronger-shelled eggs over the production period as a whole. 7. We conclude that; (a) genetic selection is extremely effective in improving bone strength and resistance to osteoporosis; (b) allowing hens freedom to exercise can also improve bone strength but may increase the risk of keel damage if they do not have genetically-improved bone status; (c) feeding hens a particulate form of limestone from 15 weeks onwards can also increase bone strength and eggshell quality; (d) genetics, environment and nutrition all have independent and additive effects on bone status in laying hens but the relative effectiveness of these factors is genetics > environment > nutrition.

Animal Feed↗
PubMed2004

Histological assessment of bioengineered new bone in repairing osteoperiosteal mandibular defects in sheep using recombinant human bone morphogenetic protein-7.

UNLABELLED: Numerous experimental studies have been published about osteoinductive bone morphogenetic proteins (BMPs). However, to our knowledge there has been no detailed histological study of a mandibular defect in a large mammal, reconstructed using BMPs. We describe here the histological features of rhBMP-7-induced bone in mandibular defects in sheep. METHODS: A 35 mm osteoperiosteal defect was created at the parasymphyseal region of the mandible in six adult sheep. The continuity of the mandible was maintained using a bony plate, and rhBMP-7 was applied on a type I collagen carrier. Bone labels were injected at selected time intervals during the follow-up period. The animals were killed after 3 months and bone samples were examined histologically, histomorphometrically, and by fluorescence microscopy. RESULTS AND CONCLUSIONS: We found a mixture of woven and lamellar bone that contained many cells with large nuclei. This had not reorganised to form cortical bone and the rhBMP-7-induced bone was more porous than the native bone. The newly-formed bone restored both endosteal and periosteal layers. rhBMP-7-induced bone was biocompatible and induced no ossification of soft tissue or abnormal growth of nearby vital structures. The mineral apposition rate was 1.98 microm/day (range 0.62-5.63 microm/day), a value close to that reported in humans. This suggests that BMPs have a limited effect in accelerating the rate of mineralisation, but promote the pre-mineralisation processes, and perhaps the formation of woven bone.

Animals↗
PubMed2004

Incidence, pathology and prevention of keel bone deformities in the laying hen.

1. As a baseline study of the nature and incidence of keel deformities in laying hens, keel condition was examined in three different strains of hen from a total of 4 different caged environments (two commercial farms and two experimental farms). Incidence of keel deformity on farms in end of lay hens ranged from 2.6 to 16.7%. Only 0.8% of younger 15-week-old pullets had deformed keels. 2. Incidence of keel deformities was unchanged in 100 birds sampled from a free-range system compared to conventional caged siblings at the same farm. 3. Keel condition was also examined in 5 selected generations of a study involving the use of a body-weight-restricted selection index for skeletal improvement. Divergent selection for skeletal characteristics decreased incidence of keel deformity and improved radiographic density (RD) in high bone index (BI) hens compared to low BI hens in all selected generations. Male high BI keels were also improved compared to low BI. Shear strength measured in normal keels in generation 6 (G6) of the genetic study was improved in high BI hens compared to low BI hens. For all hens in the genetic study, those with normal keels had stronger tibiotarsus and humerus breaking strengths than hens with deformed keels. 4. Histopathology of keels representative of different deformities showed the presence of fracture callus material and new bone in all cases. This establishes that deformities are a result of trauma and are not developmental in origin. 5. Ash contents of keels, tibiae and humeri showed no differences between hens with normal and deformed keels. There were no differences in indicators of collagen cross-linkage in other bones between hens with normal keels and those with deformed keels. 6. It is concluded that lack of bone mass is the underlying cause of keel fracture and deformity in laying hens, rather than qualitative changes in bone, and that genetic selection can improve keel quality and prevent deformity.

Animals↗
PubMed2004

High vitamin D3 requirements in broilers for bone quality and prevention of tibial dyschondroplasia and interactions with dietary calcium, available phosphorus and vitamin A.

1. Two experiments were carried out to investigate responses in performance and bone compositional and structural characteristics in broilers fed diets containing 4 concentrations of vitamin D3 (5, 20, 125 and 250 microg cholecalciferol/kg) at different concentrations of calcium, available phosphorus and vitamin A. 2. In experiment 1, body weight and tibia breaking strength were maximised at 14d with 250 microg vitamin D3/kg, tibia ash was maximised with 125 microg vitamin D3/kg. A high incidence of tibial dyschondroplasia (TD) was decreased to very low levels with 125 microg vitamin D/kg. 3. At 42d, performance and bone characteristics showed no response to vitamin D3 concentrations above 20 microg/kg. 4. Dietary vitamin A within the range 2-4 to 4.5 mg retinol/kg did not show any interaction with vitamin D3 status at either age. 5. In experiment 2, responses to vitamin D3 were strongly influenced by dietary calcium/available phosphorus. With 13 g calcium and 5 g available phosphorus/kg, performance and bone characteristics responded to vitamin D3 concentrations up to 125 microg/kg but more was needed at less optimal concentrations of calcium and available phosphorus. TD incidence was minimised with 250 microg/kg. 6. This study shows that high dietary concentrations of vitamin D3 can prevent TD. It is concluded that the vitamin D3 requirement of broilers up to 14 d of age at optimal dietary calcium and available phosphorus concentrations may be in the range 35 to 50 microg/kg for cortical bone quality and up to 250 microg/kg for prevention of TD. The vitamin D3 requirement for cortical bone quality after 14 d is not higher than 20 microg/kg. These requirements are much higher than earlier estimates and may be related to higher calcium requirements of modern broiler genotypes. Current regulations limiting maximum vitamin D3 concentrations in broiler starter diets may need to be reviewed.

Animals↗
PubMed2004

Assessing bone mineral density in vivo: digitized fluoroscopy and ultrasound.

The genetic component of osteoporosis in caged laying hens is large, and a method for detecting hens susceptible to fracture could be useful in breeding programs. A radiographic absorptiometry film method was modified by video digitization from an image intensifier and computer analysis and termed digitized fluoroscopy (DF). Humeral and ulnar DF values were measured in 165 hens during lay. Relationships (P < 0.001) were seen between DF assessments from 25 wk onward and postmortem measurements at 70 wk. We conclude that DF can detect poor bones in hens early but is problematic. Quantitative ultrasound was also investigated. We measured amplitude-dependent speed-of-sound (Ad-SoS) in the third toe in hens. Nutritional studies revealed Ad-SoS values correlated with postmortem peripheral quantitative computerized tomography, (control group, r = 0.48, P < 0.001; treatment group, r = 0.39, P < 0.001). In caged and free-range hens, Ad-SoS correlated with shear strength (r = 0.33, P < 0.001, all hens) and radiographic density values (r = 0.53, P < 0.001, all hens) measured postmortem. The Ad-SoS values were higher in free-range than in caged hens (1,904 vs. 1,850 m/s, P < 0.001). Ad-SoS measurements were made in hens from a study where divergent genetic selection has produced high and low bone index lines with 92% difference in tibia strength. The value in high bone index hens was higher than in low bone index hens at 32 (P < 0.001), 42 (P < 0.001), 52 (P < 0.05), and 62 wk (P < 0.001) in generation 8. In an Ad-SoS heritability study, heritability estimates ranged from 0.15 to 0.39. We conclude that Ad-SoS is a heritable trait, reflects other bone measurements, and rapidly detects poor bone quality in hens.

Animals↗
PubMed2003

Effects of dietary particulate limestone, vitamin K3 and fluoride and photostimulation on skeletal morphology and osteoporosis in laying hens.

1. Female chicks of a White Leghorn strain were fed three different diets from one day old: control, additional vitamin K3 (10 mg/kg), and a diet containing a combination of additional vitamin K3, sodium fluoride (10 mg/kg) and limestone in particulate rather than powdered form. At 16 weeks photoperiod was increased for half the birds from 8:16 L:D to 16:8 L:D immediately or by one hour per week to the same ultimate photoperiod for the other half. 2. Age at first egg was lower by 4.0 d for birds on the fast lighting regime but there were no overall effects of lighting on bone quality at either 25 or 70 weeks. 3. Additional vitamin K3 resulted in higher proximal tarsometatarsus cancellous bone volumes at 15 weeks and throughout the laying period compared with controls. Plasma osteocalcin concentrations were unaffected by vitamin K3 supplementation during growth. 4. The combination diet resulted in beneficial responses of 12 to 20% in most bone characteristics in hens at 70 weeks. The magnitude of these effects was similar to a previous study involving a particulate calcium source alone (Fleming et al., Poultry Science, 39: 434-440, 1998b). We conclude that the beneficial effects of the combined treatment over the lifetime of the hens were attributable mainly to the presence in the diet of a calcium source in particulate form.

Animal Feed↗
PubMed2002

Differences in composition of avian bone collagen following genetic selection for resistance to osteoporosis.

1. Collagen characteristics were compared in the tibiotarsus and humerus from 103 females and 38 males aged 68 to 72 weeks from the G6 generation of lines of laying hen selected for resistance or susceptibility to osteoporosis (high and low bone index (BI) lines). 2. Selection over the latest generation resulted in further divergence in the breaking strengths of humerus (from 12.3 to 21.8%) and tibia (from 22.3 to 37.3%) in hens. Males also showed line differences in bone strengths. 3. Plasma pyridinoline concentration was higher in hens in the low BI line, suggesting a greater rate of bone resorption in this line. 4. There were few differences between the lines in collagen and calcium concentrations in humerus and tibiotarsus cortical bone. 5. There were no differences between the lines in either sex in reduced immature collagen cross-link content of humerus or tibiotarsus. 6. Mature collagen cross-link content was higher in the high BI line in the male humerus but this effect was not apparent in the male tibiotarsus nor in either bone in the females. 7. Pyrrolic cross-link contents were higher in the high BI line in the female humerus and tibiotarsus and in the male tibiotarsus. 8. Over both lines combined, there were positive correlations between humeral and tibiotarsal pyrrole contents and strengths in females and between tibiotarsal pyrrole content and strength in males. 9. It is concluded that an increase in cross-linking, particularly pyrrolic cross-linking, in the collagen matrix contributes in part to the improvement in bone strength in the high BI line.

Amino Acids↗
PubMed2000

Prediction of breaking strength in osteoporotic avian bone using digitized fluoroscopy, a low cost radiographic technique.

Bone fragility in caged laying hens is a severe welfare problem, with fracture incidences in commercial flocks of up to 30% of all hens during their life. This fragility has been attributed to osteoporosis, the etiology of which is multifactorial in birds, as in humans, with genetic, environmental, and nutritional components. Greater understanding of the development of the disorder in hens could be obtained from the same kind of in vivo assessments available in human studies of osteoporosis. These high technology techniques for evaluation of bone mineral density (BMD), such as single or dual energy X-ray absorptiometry (SXA or DXA), quantitative computerized tomography (QCT), or attenuation by ultrasound (US), are so far not widely available to nonclinical researchers. We have modified an older X-ray film technique, radiographic absorptiometry (RA) by digitization of the analog video signal from a Philips BV-25 image intensifier, in single pulse fluoroscopy mode, and subsequent computer analysis with the public domain software package, NIH-Image 1.60. Compared with conventional RA, which uses standard X-ray film, our modified technique reduces X-ray exposure and allows the operator to digitize, store, and analyze many more images in a shorter time. We have called this modified technique "digitized fluoroscopy" (DF). In a longitudinal study of humeral radiographic density in a flock of 165 laying hens, significant relationships (P < 0.001) were observed between assessments made as early as 25 weeks, utilizing this DF technique in the humerus, and breaking strengths (and other postmortem indicators of osteoporosis) measured at 70 weeks. We conclude that DF can predict some eventual parameters of bone mass measured at 70 weeks from 25 to 40 weeks onward in bones from the same site in laying hens. The relationship between DF measurements made in the humerus and postmortem measurements of radiographic density and breaking strength made at another site (tibia) are less strong but still significant from 40 weeks onward.

Absorptiometry, Photon↗
PubMed2000

Inheritance of bone characteristics affecting osteoporosis in laying hens.

1. Heritabilities of a range of morphometric, radiological and strength characteristics were measured in the bones of end-of-lay hens. 2. Tibial strength (TSTR), humeral strength (HSTR) and keel radiographic density (KRD) were moderately to strongly inherited and were combined in a Bone Index which was used as a basis for selection. Data are available on 6 generations/cohorts of hens (n=1306), the last 3 of which are the progeny of divergently selected birds. 3. All bone characteristics used in the Bone Index responded rapidly to divergent selection and were strongly correlated with each other. In the last generation, the lines differed by 25% for TSTR, 13% for HSTR and 19% for KRD. The heritability of the index was 0.40. 4. There were no apparent genotype by environment interactions between birds housed at 2 different locations. 5. The incidence of bone fractures was significantly decreased in the line selected for high bone strength compared to the line selected for low bone strength. Humerus fracture incidence differed by a factor of 6 between the lines in the last generation. There was a strong quadratic relationship between tibia strength and overall fracture incidence (r2=0.92, P<0.01). 6. The results imply that selection for enhanced bone strength can be used as a long-term strategy for alleviating the problems of osteoporosis in laying hens.

Animal Husbandry↗
PubMed2000

Osteoporosis in cage layers.

Osteoporosis in laying hens is a condition that involves the progressive loss of structural bone during the laying period. This bone loss results in increased bone fragility and susceptibility to fracture, with fracture incidences of up to 30% over the laying period and depopulation not uncommon under commercial conditions. A major cause of osteoporosis is the switch in bone formation from structural to medullary bone at the onset of sexual maturity, but structural bone loss is accelerated by the relative inactivity of-caged birds. Allowing birds more exercise, as in aviary systems, results in better bone quality but may not decrease the overall fracture incidence. Good nutrition can help to minimize osteoporosis but is unable to prevent it. Best nutritional practice involves transferring birds to a higher calcium diet at lighting up rather than at first egg, providing a source of calcium in particulate form, and not withdrawing feed some days before depopulation. Breeding may be an effective way of combating ostoporosis. Some bone strength traits have been shown to be heritable, and divergent selection for resistance or susceptibility to osteoporosis has resulted in lines with markedly different bone characteristics. After three generations of selection, the lines differ by 19% for keel bone mineral density, 13% for humerus breaking strength, and 25% for tibia breaking strength and show a sixfold difference in fracture incidence under commercial breeding conditions. The difference in bone quality among the lines is maintained under different housing systems.

Animal Nutritional Physiological Phenomena↗
PubMed1998

Bone structure and strength at different ages in laying hens and effects of dietary particulate limestone, vitamin K and ascorbic acid.

1. A range of bone structural and strength characteristics was determined in laying hens at 15, 25, 50 and 70 weeks of age. The birds were fed up to 25 weeks on diets supplemented with additional vitamin K (10 mg menadione/kg) or ascorbic acid (250 mg/kg) or up to 70 weeks on diets containing limestone in powder or particulate form. 2. There were important effects of age on all bone characteristics. Between 15 and 25 weeks there was a rapid loss of cancellous bone and a rapid accumulation of medullary bone in the proximal tarsometatarsus (PTM). These changes continued at a slower rate up to 70 weeks. Cancellous bone content of the free thoracic vertebra (FTV) also declined after 15 weeks. 3. Breaking strengths of tibia and humerus did not change between 15 and 25 weeks but decreased later in lay. 4. None of the nutritional treatments affected bone characteristics at 15 weeks of age. 5. Increasing the dietary vitamin K supplement from 2 to 12 mg menadione/kg increased cancellous bone volume in the PTM at 25 weeks. 6. Dietary ascorbic acid did not affect any of the bone characteristics measured up to 25 weeks. 7. Particulate limestone resulted in a smaller loss of cancellous bone between 15 and 25 weeks and increased accumulation of medullary bone in the PTM. Breaking strength of the tibia and radiographic densities of tibia and keel were also improved. 8. It is concluded that patterns of bone loss over the lifetime of laying hens vary, depending upon the bone type. Feeding a particulate source of calcium can help to alleviate some of the characteristics of osteoporosis. Supplementation with extra vitamin K may also be beneficial.

Aging↗
PubMed1997

Studies on effects of nutritional factors on bone structure and osteoporosis in laying hens.

1. A modern hybrid strain of laying hen (Hisex) was fed from point of lay to 68 weeks on a control diet and diets containing oystershell, fluoride, 1,25-dihydroxycholecalciferol, ascorbic acid, a lower concentration of phosphorus and a combination of a lower concentration of crude protein and higher concentration of vitamin K. Hens from a much older strain (Brown Leghorn J-line) were fed on the control diet. 2. Plasma variables were measured during lay. End-of-lay trabecular and medullary bone volumes in the proximal tarsometatarsus and free thoracic vertebra were measured by histomorphometry. 3. The majority of Hisex hens were considered to be osteoporotic by the end of lay. In contrast, none of the J-line were osteoporotic. 4. None of the nutritional treatments affected trabecular bone volumes. Medullary bone volumes were increased significantly by feeding oystershell or fluoride. 5. There was no phenotypic correlation between egg production and trabecular bone volume in the Hisex hens. 6. The experiment provided evidence that osteoporosis in laying hens, as assessed by trabecular bone volumes, is not caused by calcium deficiency and could not be prevented by any of the nutritional treatments studied.

Animal Nutritional Physiological Phenomena↗
PubMed1995

Biochemical changes in the collagenous matrix of osteoporotic avian bone.

No detailed biochemical analysis has been carried out of the compositional changes in the collagen matrix of avian bone in relation to increased bone fragility in osteoporosis. We have shown that osteoporosis in avian bone is certainly not just a simple loss of apatite and collagen, but involves significant changes in the biochemistry of the collagen molecule and consequently in the physical properties of the fibre. The decreased mechanical strength and the change in the thermal stability can be directly related to changes in post-translational modifications, i.e. lysine hydroxylation and the intermolecular cross-link profile. The increased hydroxylation and change in cross-linking are consistent with increased turnover of the collagen, possibly in an attempt to initiate a repair mechanism which, in fact, leads to an acceleration in the increase in fragility of the bone. Clearly there are post-translational modifications of the newly synthesized collagen in avian osteoporosis, and these changes may play a role in the pathogenesis of the disease.

Animals↗
PubMed1994

Fullerenes in an impact crater on the LDEF spacecraft.

The fullerenes C60 and C70 have been found to occur naturally on Earth and have also been invoked to explain features in the absorption spectra of interstellar clouds. But no definitive spectroscopic evidence exists for fullerenes in space and attempts to find fullerenes in carbonaceous chondrites have been unsuccessful. Here we report the observation of fullerenes associated with carbonaceous impact residue in a crater on the Long Duration Exposure Facility (LDEF) spacecraft. Laser ionization mass spectrometry and Raman spectroscopy indicate the presence of fullerenes in the crater and in adjacent ejecta. Man-made fullerenes survive experimental hypervelocity (approximately 6.1 km s-1) impacts into aluminium targets, suggesting that space fullerenes contained in a carbonaceous micrometeorite could have survived the LDEF impact at velocities towards the lower end of the natural particle encounter range (<13 km s-1). We also demonstrate that the fullerenes were unlikely to have formed as instrumental artefacts, nor are they present as contaminants. Although we cannot specify the origin of the fullerenes with certainty, the most plausible source is the chondritic impactor. If, alternatively, the impact produced the fullerenes in situ on LDEF, then this suggests a viable mechanism for fullerene production in space.

Aluminum↗
PubMed1994

Primary bronchogenic carcinoma in the heart transplant recipient.

An increased risk of neoplasia is a well-recognized complication of chronic immunosuppression. Although lung cancer has been sporadically reported in the transplant population, it has not been recognized widely as a specific risk among heart transplant recipients. We present 3 cases of bronchogenic carcinoma in cardiac transplant patients, discuss possible risk factors, and outline recommendations for diagnosis and management of new lung lesions discovered during routine follow-up.

Aged↗