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R Travers

Publications and source records attributed to R Travers.

At least 37 records · Page 2Linked to original sources
PubMed1999

The mineralization density of iliac crest bone from children with osteogenesis imperfecta.

We studied iliac crest biopsy cores taken from young individuals with osteogenesis imperfecta of several types, and from age-matched normals; the same samples had been used in prior studies using conventional light microscopic histomorphometric procedures. The PMMA blocks were micro-milled to a fine finish, carbon coated, and imaged using backscattered electrons (BSE) in an automated digital scanning electron microscope (SEM). For comparison of BSE signal levels between samples, microscope operation parameters were standardized by reference to halogenated dimethacrylate standards, and recording data from stereological arrays of 512*512 nonoverlapping pixels at 3.5 micrometer separation. All OI types showed higher average mineralization densities than age- and site-matched normals. This is interpreted as the result of the failure in matrix assembly, such that it has a higher water volume fraction available for mineral deposition. Added to the net deficit in bone quantity, the predicted higher stiffness of the more mineralized bone will account for much of the observed 'brittleness' that characterizes this class of genetic disease. The mean mineralization density, which was higher in types III, IV, and V than in type I, appears to be correlated with disease severity.

Adolescent↗
PubMed1999

Ecthyma gangrenosum in an AIDS patient with normal neutrophil count.

Ecthyma gangrenosum is the cutaneous manifestation of Pseudomonas aeruginosa septicemia, typically affecting immunosuppressed patients, particularly those with neutropenia. Association with HIV disease has been rarely reported. We describe an unusual presentation of solitary ecthyma gangrenosum on the face of a non-neutropenic patient with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1999

Engineering bone regeneration with bioabsorbable scaffolds with novel microarchitecture.

Critical-sized defects (CSDs) were introduced into rat calvaria to test the hypothesis that absorption of surrounding blood, marrow, and fluid from the osseous wound into a bioabsorbable polymer matrix with unique microarchitecture can induce bone formation via hematoma stabilization. Scaffolds with 90% porosity, specific surface areas of approximately 10 m2/g, and median pore sizes of 16 and 32 microm, respectively, were fabricated using an emulsion freeze-drying process. Contact radiography and radiomorphometry revealed the size of the initial defects (50 mm2) were reduced to 27 +/- 11 mm2 and 34 +/- 17 mm2 for CSDs treated with poly(D,L-lactide-co-glycolide). Histology and histomorphometry revealed scaffolds filled with significantly more de novo bone than negative controls (p < 0. 007), more osteoid than both the negative and autograft controls (p < 0.002), and small masses of mineralized tissue (< 15 mm in diameter) observed within the scaffolds. Based on these findings, we propose a change in the current paradigm regarding the microarchitecture of scaffolds for in vivo bone regeneration to include mechanisms based on hematoma stabilization.

Absorbable Implants↗
PubMed1998

Cyclic administration of pamidronate in children with severe osteogenesis imperfecta.

BACKGROUND: Severe osteogenesis imperfecta is a disorder characterized by osteopenia, frequent fractures, progressive deformity, loss of mobility, and chronic bone pain. There is no effective therapy for the disorder. We assessed the effects of treatment with a bisphosphonate on bone resorption. METHODS: In an uncontrolled observational study involving 30 children who were 3 to 16 years old and had severe osteogenesis imperfecta, we administered pamidronate intravenously (mean [+/-SD] dose, 6.8+/-1.1 mg per kilogram of body weight per year) at 4-to-6-month intervals for 1.3 to 5.0 years. Clinical status, biochemical characteristics reflecting bone turnover, the bone mineral density of the lumbar spine, and radiologic changes were assessed regularly during treatment. RESULTS: Administration of pamidronate resulted in sustained reductions in serum alkaline phosphatase concentrations and in the urinary excretion of calcium and type I collagen N-telopeptide. There was a mean annualized increase of 41.9+/-29.0 percent in bone mineral density, and the deviation of bone mineral density from normal, as indicated by the z score, improved from -5.3+/-1.2 to -3.4+/-1.5. The cortical width of the metacarpals increased by 27+/-20.2 percent per year. The increases in the size of the vertebral bodies suggested that new bone had formed. The mean incidence of radiologically confirmed fractures decreased by 1.7 per year (P<0.001). Treatment with pamidronate did not alter the rate of fracture healing, the growth rate, or the appearance of the growth plates. Mobility and ambulation improved in 16 children and remained unchanged in the other 14. All the children reported substantial relief of chronic pain and fatigue. CONCLUSIONS: In children with severe osteogenesis imperfecta, cyclic administration of intravenous pamidronate improved clinical outcomes, reduced bone resorption, and increased bone density.

Adolescent↗
PubMed1998

Paediatric HIV infection in the Republic of Ireland and the need for antenatal screening.

Thirty-seven HIV-infected children have been identified in the Republic of Ireland since 1985. Only 12 (32%) of 37 were followed prospectively from birth. Median age at diagnosis was 18 months (4 weeks to 8 years). In 32 (86%) of 37 cases, HIV infection was acquired as a result of transmission from mother to infant with intravenous drug use (IVDU) the most frequent risk factor for maternal acquisition of HIV. Of these 32 children, median maternal age at delivery was 24 (interquartile range (IQR) 23-26) years with median gestation at delivery 40 (IQR 38-40) weeks. Mode of delivery was by vaginal delivery in all 29 (91%) cases where mode of delivery is known. Only 2 infants were breastfed. Seven children have died at a median age of 9 (0.8-9.6) years. As of July 1997, 12 children have AIDS, 14 have symptomatic disease without AIDS and 3 are asymptomatic. Median age at AIDS diagnosis was 2.6 (0.1-6.5) years. Median survival time post-AIDS diagnosis was 6.5 (1.8-8.3) years. Of 29 living children, 24 mothers and 14 fathers are HIV infected and only 14 children live with both parents. Childhood HIV infection has had a significant personal, social and financial impact on both Irish families and society in general. More effective measures to control HIV infection among intravenous drug users are needed. Antenatal detection of HIV-infected mothers is paramount as vertical transmission can be successfully prevented and morbidity and death can be prevented in the infected infant.

Child↗
PubMed1996

24,25 Dihydroxyvitamin D supplementation corrects hyperparathyroidism and improves skeletal abnormalities in X-linked hypophosphatemic rickets--a clinical research center study.

Therapy for X-linked hypophosphatemia (XLH) only partially corrects skeletal lesions and is often complicated by hyperparathyroidism. 24,25(OH)2 D3 improves skeletal lesions in a murine model of XLH and suppresses PTH secretion in animals. Therefore, we undertook a placebo-controlled trial of 24,25(OH)2 D3 supplementation to standard treatment in patients with XLH to improve bone disease and reduce hyperparathyroid complications. Fifteen subjects with XLH receiving standard treatment [1,25(OH)2 D3 or dihydrotachysterol plus phosphate] were evaluated, supplemented with placebo, and reevaluated one yr later. 24,25(OH)2 D3 supplementation was then begun and studies repeated after another year. Each patient underwent a detailed evaluation of calcium homeostasis over a 24-h period. Rachitic abnormalities were assessed radiographically in children. Adults underwent bone biopsies. 24,25(OH)2 D3 normalized PTH values in nine subjects (peak PTH was 46.5 +/- 6.6 pmol/L at entry, 42.3 +/- 5.9 pmol/L after placebo, and 23.3 +/- 5.4 pmol/L after 24,25(OH)2 D3). Nephrogenous cAMP decreased at night, coincident with the decrease in PTH, and serum phosphorus was slightly greater with 24,25(OH)2 D3. Radiographic features of rickets improved during 24,25(OH)2 D3 supplementation in children, and osteoid surface decreased in adults. 24,25(OH)2 D3 is a useful adjunct to standard therapy in XLH by effecting correction of hyperparathyroidism and improvement of rickets and osteomalacia.

24,25-Dihydroxyvitamin D 3↗
PubMed1995

Effect of 1,25-dihydroxyvitamin D3 treatment on bone formation by transplanted cells from normal and X-linked hypophosphatemic mice.

Bone cells isolated from the Hyp mouse, the murine homologue for hypophosphatemic vitamin D-resistant rickets, produce abnormal bone when transplanted to either normal or phosphate-supplemented Hyp mice. To assess whether correction of the bone formation by mutant cells transplanted into either normal or Hyp mice could be achieved in the presence of supraphysiologic serum concentrations of 1.25-dihydroxyvitamin D3 (1.25-(OH)2D3), recipient mice of both genotypes were infused continuously with 1.25-(OH)2D3 (0.2 micrograms/kg/day). Bone nodules present in transplants recovered after 14 days were characterized by measuring the osteoid thickness and volume. Administration of 1.25-(OH)2D3 to Hyp mice corrected the defective bone formation by normal cells but not by pair-transplanted Hyp cells, despite normalization of serum phosphate levels and 3-fold increases in serum 1.25-(OH)2D3. The osteoid thickness and volume in Hyp transplants into 1.25-(OH)2D3-treated Hyp mice were, however, markedly reduced down to values observed for Hyp transplants into recipient normal mice. Administration of 1.25-(OH)2D3 to normal mice improved further bone formation by mutant cells without affecting that by pair-transplanted normal cells. Administration of 24.25-(OH)2D3 (1 microgram/kg/day) combined with 1.25-(OH)2D3 to recipient mice of both genotypes prevented the sharp fall in serum 24.25-(OH)2D3 but was not more beneficial than 1.25-(OH)2D3 alone for improving bone formation by transplanted Hyp cells. These observations demonstrate an abnormal response of the mutant cells to the extracellular environment and support the concept of an intrinsic osteoblast defect in the Hyp mouse.

24,25-Dihydroxyvitamin D 3↗
PubMed1992

Defective bone formation by Hyp mouse bone cells transplanted into normal mice: evidence in favor of an intrinsic osteoblast defect.

The hypophosphatemic (Hyp) mouse is an animal model for human hypophosphatemic vitamin D-resistant rickets. We have reported that bone cells isolated from Hyp mice born to homozygous mutant females produce abnormal bone when transplanted into normal mice. To test whether an environmentally acquired defect of the mutant cells contributed to the impaired bone formation observed in transplants, periostea and osteoblasts from normal and Hyp littermates were transplanted intramuscularly into normal animals. To test more specifically for an hypophosphatemia-induced cell alteration before transplantation, bone cells isolated from phosphate-depleted normal mice were transplanted into normal animals. The bone nodules formed in 2 week transplants were characterized by measuring their osteoid thickness and volume. Impaired bone formation was evidenced in Hyp transplants compared to normal littermate transplants by increased osteoid thickness and volume. In contrast to cells from mutant mice, cells isolated from normal mice with comparable hypophosphatemia produced normal bone. These results indicate that the inability of Hyp osteoblasts to produce normal bone when placed in a normal environment is not the consequence of prior exposure to an altered environmental but likely of an intrinsic cellular abnormality. These observations add further support to the concept that the osteoblast is an important target for the Hyp mutation.

Animals↗
PubMed1992

Effect of dietary phosphate deprivation and supplementation of recipient mice on bone formation by transplanted cells from normal and X-linked hypophosphatemic mice.

The hypophosphatemic (Hyp) mouse is the murine homolog for human hypophosphatemic vitamin D-resistant rickets. We previously reported that bone cells isolated from normal and Hyp mice produced abnormal bone when transplanted intramuscularly into mutant mice. To assess the role of hypophosphatemia on bone formation in transplants, normal and Hyp mouse periostea were pair transplanted into control or phosphate (P)-supplemented Hyp mice and into control or P-deprived normal mice. The bone nodules formed in transplants after 2 weeks were characterized by measuring the thickness of the surrounding osteoid seams and the relative osteoid volume. P restriction in normal recipient mice impaired bone formation by transplanted normal cells and aggravated the defective bone formation by Hyp cells. The osteoid thickness and volume remained significantly higher in Hyp transplants than in normal cotransplants, however. P supplementation of Hyp recipient mice normalized bone formation by transplanted normal cells but not by Hyp cells. However, a marked decrease in osteoid thickness and volume was observed in Hyp transplants down to values observed in normal recipient mice. These results indicate that hypophosphatemia is not the only cause of abnormal bone formation in the Hyp mouse but that an osteoblast dysfunction contributes to the bone disease. These observations further support the concept that the osteoblast may be an important target for the Hyp mutation.

Animals↗
PubMed1992

A prospective trial of phosphate and 1,25-dihydroxyvitamin D3 therapy in symptomatic adults with X-linked hypophosphatemic rickets.

Current treatment of X-linked hypophosphatemia (XLH) employs the combined administration of oral phosphate and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Although this drug regimen significantly improves the clinical course of the disease in children, the value of medical treatment in symptomatic adults with XLH has not been established. We, therefore, investigated the clinical, biochemical, and histological responses to phosphate and 1,25-(OH)2D3 in 16 symptomatic adult patients with XLH followed for a mean of 4.2 yr. Eighty-seven percent of the patients had an improvement in bone or joint pain with therapy. There was a significant increase in mean serum phosphate (from 0.61 +/- 0.03 to 0.77 +/- 0.03 mmol/L) and urinary calcium excretion (from 2.45 +/- 0.38 to 4.39 +/- 0.44 mmol/day) with treatment. Pretreatment bone biopsies demonstrated findings characteristic of osteomalacia, including abnormally increased osteoid volume and decreased mineral apposition rates. Treatment was accompanied by a significant decrease in osteoid thickness as well as a reduction in mean osteoid volume. However, therapy did not completely normalize these parameters. Disease severity, as assessed by histomorphometric parameters, did not correlate with any pretreatment serum or urinary biochemical measurement, but did seem to correlate with symptom score. Although most patients tolerated therapy without difficulty, 1 patient developed tertiary hyperparathyroidism during treatment and renal insufficiency that progressed despite cessation of therapy. This study provides evidence that therapy with oral phosphate and 1,25-(OH)2D3 in symptomatic adults with XLH can result in significant clinical and histomorphometric improvement.

Adolescent↗
PubMed1991

Dynamic histomorphometric evaluation of human fetal bone formation.

We have evaluated dynamic and static parameters of bone formation in femoral metaphyses collected from two human fetuses at 19 weeks of gestation. Tetracycline was administered to the mother at set intervals (2-5-2 day schedule) before interruption of pregnancy. Labels were distinct and sharply linear, suggesting a well organized calcification front at this early stage of mineralization. Mineral apposition rate (MAR) was fastest (4.1 +/- 0.3 microns/d) in the periosteal (Ps) envelope, and about half that value in the endosteal envelopes (endocortical: 2.5 +/- 0.1, cancellous 2.1 +/- 0.1 microns/d). Because cellular activities may vary throughout the metaphyseal area, sections were arbitrarily separated in 0.75 mm layers starting from the growth plate. Three measured parameters decreased rapidly with increasing distance from the physis: Ps MAR: 4.9 to 2.3 microns/d, trabecular osteoid thickness: 5.9 to 1.2 microns, and cartilage volume (CgV/TV): 5.4% to 1.2%. Others did not vary significantly along the metaphysis. Comparison of several static parameters with those measured in five autopsy specimens from full-term infants showed that bone and cartilage volume, and trabecular thickness increased while osteoid thickness and parameters of resorption decreased in the second half of the gestation period. The study indicates that fetal bone matrix mineralization is already highly organized at mid-gestation, and validates the use of histomorphometry to assess bone maturation during early skeletal development.

Bone Development↗
PubMed1991

Affect logic.

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Affective Symptoms↗