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Biomedical subjects

U M Davies

Publications and source records attributed to U M Davies.

14 recordsLinked to original sources

Bone mineral content and bone mineral metabolism: changes after growth hormone treatment in juvenile chronic arthritis.

OBJECTIVE: To determine whether growth hormone (rhGH) affects bone mineral metabolism and bone mineral content (BMC, g/cm) in a therapeutic trial of recombinant growth hormone in growth retarded children with juvenile chronic arthritis (JCA) treated with steroid. METHODS: BMC was measured in 20 children (of whom 17 were treated with corticosteroid) before and after one year of rhGH. Children were randomized to receive either low dose (12 IU/m2/week) or high dose (24 IU/m2/week) for one year. Three monthly assessments were made of disease activity and anthropomorphic measurements. Blood and urine samples were also obtained to measure indicators of disease activity, bone remodeling, and vitamin D and parathyroid hormone (PTH) status. RESULTS: BMC increased during the treatment period and correlated with increasing height. Osteocalcin levels, normally indicators of bone formation, increased after rhGH treatment and correlated significantly with height velocity, particularly for the high dose treatment group. In contrast, osteocalcin levels were negatively correlated with C-reactive protein levels, both before and during treatment. Height velocity, vitamin D, PTH, and osteocalcin levels were significantly lower than age matched controls before treatment. CONCLUSION: Steroid treated children with both JCA and severe growth retardation have reduced vitamin D, PTH, and osteocalcin levels. After treatment with rhGH, height velocity increased, as did BMC. Growth hormone might be a useful adjunct in the treatment of severe growth retardation and osteoporosis in children with JCA. The longterm benefits of rhGH in the treatment of osteoporosis remain unclear.

Adolescent↗

Juvenile rheumatoid arthritis. Effects of disease activity and recombinant human growth hormone on insulin-like growth factor 1, insulin-like growth factor binding proteins 1 and 3, and osteocalcin.

OBJECTIVE: To investigate possible mechanisms of growth impairment in children with juvenile rheumatoid arthritis (JRA). METHODS: Eighteen prepubertal children with JRA and growth retardation received recombinant human growth hormone (rHuGH) for 1 year. Growth hormone profiles over 24 hours were obtained before treatment in 12 patients; the levels did not differ from those in "short normal" children. Levels of insulin-like growth factor 1 (IGF-1), IGF binding proteins (IGFBPs) 1 and 3, insulin, osteocalcin, and C-reactive protein (CRP), as well as the erythrocyte sedimentation rate were measured serially. Pretreatment levels were compared with control levels. RESULTS: In JRA patients, IGF-1, IGFBP-3, and osteocalcin levels were significantly lower and insulin levels significantly higher than those in controls, but there was no significant difference in the level of IGFBP-1. With rHuGH treatment, height velocity and mean levels of IGF-1, osteocalcin, and insulin increased significantly, while mean levels of IGFBP-1 fell significantly. Levels of IGFBP-3 correlated with those of IGF-1. The height velocity correlated positively with IGF-1 and osteocalcin, and negatively with IGFBP-1. Levels of IGFBP-1 were inversely related to those of insulin and IGF-1. There was a significant negative correlation between the CRP and height velocity, IGF-1 level, and osteocalcin level. CONCLUSION: IGF-1 production is impaired in children with active JRA. Treatment with a therapeutic dose of rHuGH can rectify the IGF-1 deficiency within 4 days, but its effect is adversely influenced by the acute-phase response, as reflected by an elevated CRP level.

Analysis of Variance↗

Treatment of growth retardation in juvenile chronic arthritis with recombinant human growth hormone.

OBJECTIVE: To evaluate the effect of recombinant human growth hormone (rhGH) on the linear growth of children with persistently active juvenile chronic arthritis (JCA), most of whom were receiving steroid therapy. All of them were severely growth retarded, but had adequate GH secretion. METHODS: After monitoring height velocity for one year, children were treated for the following year with either 12 IU/m2 or 24 IU/m2 of rhGH. During this period disease activity, drug treatment, dietary intake and bone maturation as well as linear growth were documented. RESULTS: There was a significant increase in height velocity in almost all children during the treatment period. Children with mild to moderate disease activity grew at a better rate than those with very active disease. Children with polyarticular disease responded better than those with systemic JCA. Those children receiving high dose rhGH grew significantly more than those on the low dose regimen. Bone maturation did not exceed chronological age. CONCLUSION: We conclude the rhGH significantly increases the height velocity during one year of treatment. However, its effect on ultimate adult height remains unknown. Thus extensive longterm studies are required to evaluate the risk benefit ratio of this costly treatment.

Adolescent↗

hPTH 1-34 treatment of osteoporosis with added hormone replacement therapy: biochemical, kinetic and histological responses.

Twelve patients with vertebral fracture osteoporosis were recruited into a trial of treatment with hPTH 1-34 by daily injection for 1 year combined (from the 5th month) with an anti-resorptive agent (oestrogen, n = 9; nandrolone, n = 3). Treatment outcomes were monitored by biochemical and radiotracer measurements together with histomorphometry of transiliac biopsies before and at the end of treatment following double in vivo pre-labelling with demethylchlortetracycline. Indices of whole body bone formation, obtained from the analysis of 85Sr data, showed substantial increases (P less than 0.005) for all three indices measured) while biochemical (hydroxyproline) and kinetic measurements of bone resorption showed modest and equivocal changes only. As a result calcium balance improved. Gastrointestinal calcium absorption showed a tendency to improve, while urine calcium decreased; but these changes were statistically not significant except for radiocalcium absorption in the oestrogen treated subgroup. Histomorphometry revealed substantial increases in cancellous bone volume as reported previously with hPTH 1-34 given alone. However, iliac (as distinct from whole body) indices related to bone formation and resorption appeared to have returned towards pre-treatment values by the time of the second biopsy under the influence of the anti-resorptive agent given with the hPTH 1-34. It is confirmed that hPTH 1-34 therapy can increase iliac cancellous bone mass (as well as spinal cancellous bone mass as reported earlier) without a long-term increment in whole body bone resorption, providing the hPTH is combined with an anti-resorptive agent.

Aged↗

Treatment of osteoporosis with human parathyroid peptide and observations on effect of sodium fluoride.

OBJECTIVE: To evaluate the need for a randomised study of treatment of spinal osteoporosis with human parathyroid peptide in the secondary prevention of crush fractures; to study the effect of human parathyroid hormone peptide 1-34 plus sex hormones on vertebral body cancellous bone; and, separately, to determine the effect of relatively low doses of sodium fluoride plus calcium on spinal bone mineral density. DESIGN: Open study of patients with primary or postmenopausal osteoporosis. All patients had serial bone densitometry of the spine by quantitative computed tomography and dual photon absorptiometry as well as serial densitometry of the radial midshaft (cortical) and radial distal (trabecular) bone by quantitative computed tomography. Changes in the spinal bone not forming the spongiosa of the vertebral bodies ("cortical" bone) were determined from the difference between the two axial measurements, after correction to the same units of measurement. SETTING: Northwick Park Hospital and Medical Research Council Clinical Research Centre. PATIENTS: 24 Patients who fulfilled the conventional criteria for type 1 (vertebral) osteoporosis not secondary to recognised causes other than sex hormone deficiency and with at least one crush or wedge vertebral fracture and a spinal bone density (quantitative computed tomography) less than 80 mg/cm3 or two or more fractures. Twelve patients received human parathyroid peptide and 12 sodium fluoride; they were not randomised. MAIN OUTCOME MEASURES: Trends in axial and peripheral bone mass values determined by linear, time dependent regression analyses. RESULTS: The patients receiving the peptide showed a substantial increase in vertebral spongiosa (mean 25.6 mg/cm2 two years after the start of treatment). No significant changes were seen in spinal cortical or radial bone density. The patients receiving sodium fluoride showed roughly equal increases in cancellous and cortical bone over the same period (mean increase in vertebral spongiosa 16.1 mg/cm3). No significant changes were seen in radial bone. CONCLUSIONS: Treatment of postmenopausal women with human parathyroid peptide selectively increases spinal cancellous bone density by amounts that may prove useful in secondary prevention. Peptide treatment should now be tested in a randomised study in which the important end point is prevention of fractures as the usefulness of sodium fluoride in this context is doubtful.

Bone Density↗

Metronidazole resistant Bacteroides fragilis infection of a prosthetic hip joint.

A case of infection involving a prosthetic joint in a patient with adult Still's Disease is described. The causative organism was a strain of Bacteroides fragilis which was resistant to metronidazole. The rarity of this occurrence is emphasised. Diagnostic difficulties which arose are described and the problems encountered with therapy discussed.

Administration, Oral↗

Treatment with acyclovir does not affect orogenital ulcers in Behçet's syndrome: a randomized double-blind trial.

Acyclovir is a potent antiviral drug, of proven efficacy in the treatment of herpes simplex virus infection. Since this virus has been implicated in the aetiology of Behçet's syndrome, the effect of acyclovir on orogenital ulceration in this condition was determined in a randomized, double-blind, placebo-controlled, crossover trial. Eighteen of 22 patients entering the study completed the trial. Treatment with acyclovir failed to alleviate the frequency and severity of orogenital ulceration or other disease features.

Adolescent↗

Infection of a prosthetic knee joint with Peptostreptococcus magnus.

Infection of a prosthetic knee joint with Peptostreptococcus magnus in an immunosuppressed patient with rheumatoid arthritis is described. The organism is a skin commensal, generally thought to be of low pathogenicity; the difficulty in making the diagnosis is emphasised.

Arthritis, Rheumatoid↗