Search PubMed⌕ Search

Biomedical subjects

S T Harris

Publications and source records attributed to S T Harris.

At least 37 records · Page 2Linked to original sources
PubMed1994

Monitoring bone resorption in early postmenopausal women by an immunoassay for cross-linked collagen peptides in urine.

A new immunoassay using an ELISA approach for measuring urinary excretion of cross-linked N-telopeptides of type 1 collagen was evaluated as a specific measure of bone resorption. The assay was applied to 65 early postmenopausal women who participated in a placebo-controlled trial of the aminobisphosphonate, alendronate sodium. Eight blood and urine samples were collected over a 9 month interval. Baseline cross-linked peptide excretion varied from 26 to 216 pmol BCE (bone collagen/mumol Cr. Within-subject variability (CV) for cross-linked peptide excretion was 20.2% over the 9 months in placebo-treated subjects, substantially less than that observed for other biochemical markers of bone resorption: 45, 53, and 63% for fasting urinary calcium and hydroxyproline and 24 h urinary lysylpyridinoline (HPLC assay), respectively. Baseline cross-linked peptide excretion correlated significantly (p < 0.001) with baseline total urine lysylpyridinoline and serum osteocalcin, but not with the other biochemical markers. Initial peptide excretion also correlated inversely with lumbar spine bone mineral density at entry (r = -0.26, p < 0.05). Treatment for 6 weeks with alendronate produced a dose-dependent suppression of cross-linked peptide excretion (0 +/- 8, 29 +/- 6, 56 +/- 5, and 64 +/- 3% for 0, 5, 20, and 40 mg, respectively, p < 0.01 versus placebo for treatment effect), with a return toward pretreatment values during follow-up. Measurement of the urinary cross-linked N-telopeptides of type I collagen by this new ELISA approach appears promising as a simple and reliable method to assess overall bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Alendronate↗
PubMed1993

The crisis in Bosnia: breaking down barriers.

Since the outbreak of war in the former Yugoslavia, the British Government has accepted a number of people with special humanitarian needs from Bosnia. In October 1992, seven families, comprising of ten adults aged between 24 and 42 years old and 13 children aged between 18 months and 15 years old, arrived in Surrey having sought the status of 'war refugee' by the Home Office.

Adolescent↗
PubMed1993

Short-term effect of alendronate on bone mass and bone remodeling in postmenopausal women.

The short-term dose-response relationship between treatment with the bisphosphonate alendronate, biochemical markers of bone turnover, and changes in lumbar spine bone mineral density (BMD) over 9 months was assessed using a double-masked controlled study design in 65 postmenopausal women (mean age 51.6 years, mean 1.5 years since last menses) receiving 5, 20, 40 mg of alendronate or placebo for 6 weeks. After 6 weeks of alendronate, serum calcium phosphate and osteocalcin decreased, and intact parathyroid hormone increased significantly in dose-dependent fashions in the alendronate-treated groups (T) compared with placebo (P). Generally similar changes (decreases) were noted in 24-h urinary calcium and pyridinoline (deoxy- and hydroxylysl pyridoline); by 30 weeks post-treatment no significant changes from baseline or between T and P were noted. Lumbar BMD by dual-energy X-ray absorptiometry demonstrated a dose-dependent response over 9 months (median % change +/- SD: -1.2 +/- 0.9 for 5 mg T, +0.7 +/- 0.8 for 20 mg T*, +1.2 +/- 1.1 for 40 mg T*;*p < 0.01 vs P). Alendronate was generally well tolerated over all dosages. These data demonstrate that short-term (6 weeks) oral alendronate treatment (5-40 mg daily) is well tolerated and effective in (reversibly) decreasing biochemical markers of bone turnover in early postmenopausal women, and in stabilizing spinal BMD over 9 months. Longer-term treatment with larger clinical populations is indicated to define more fully the potential efficacy and safety of chronic alendronate therapy.

Alendronate↗
PubMed1993

Four-year study of intermittent cyclic etidronate treatment of postmenopausal osteoporosis: three years of blinded therapy followed by one year of open therapy.

PURPOSE: To determine the effect of long-term intermittent cyclic etidronate treatment on spinal bone density and vertebral fracture rates. PATIENTS AND METHODS: Postmenopausal osteoporotic women (n = 423) were randomized initially into a 2-year, double-blind, multicenter study; it was extended to a third year of blinded treatment followed by open-label treatment: 357 patients continued treatment in Year 3 (305 receiving blinded therapy and 52 receiving calcium supplementation) and 277 in Year 4. During Years 1 through 3, patients received double-blind treatment with phosphate (1.0 g) or placebo twice daily for 3 days, etidronate (400 mg) or placebo daily for 14 days, and calcium (500 mg) daily for the remainder of each 91-day treatment cycle. During Year 4, open-label intermittent cyclic etidronate therapy (without preceding phosphate) was administered to all patients. Spinal bone density and vertebral fracture rates were the main outcome measures. RESULTS: During Year 3, etidronate therapy maintained the significant increases in spinal bone mineral density of the first 2 years. Over the 3-year period, proximal femur bone density increased in etidronate-treated patients. Etidronate therapy for 3 years significantly decreased the vertebral fracture rate in patients at higher risk for fracture (low spinal bone density and three or more vertebral fractures at study entry), as compared with nonetidronate treatment (228 versus 412 fractures per 1,000 patient-years, respectively; p < 0.05). After 1 year of open-label treatment, patients previously treated with etidronate maintained bone mass, and vertebral fracture rates in all groups were lower than in any other study period. There were no apparent serious adverse effects. CONCLUSIONS: Three years of intermittent cyclic etidronate therapy produced significant increases in spinal and hip bone density, with a significant reduction in vertebral fracture rates in patients at higher fracture risk. Maintenance of bone mass and low fracture rate were observed when etidronate was continued for an additional year.

Analysis of Variance↗
PubMed1993

The effect of short term treatment with alendronate on vertebral density and biochemical markers of bone remodeling in early postmenopausal women.

The effects of oral alendronate treatment on spinal bone mineral density and biochemical markers of bone turnover were assessed in women in the early postmenopausal period. Sixty-five women were treated with placebo or 5, 20, or 40 mg alendronate daily for 6 weeks in a double blind study. Treatment with alendronate decreased both urinary markers of bone resorption (pyridinolines, hydroxyproline, and calcium) and serum markers of bone formation (osteocalcin and alkaline phosphatase) in a dose-dependent fashion. This short term treatment with alendronate also produced a dose-dependent increase in lumbar bone mineral density measured 7.5 months after the completion of therapy. Median percent changes in integral spinal bone mineral density, as assessed by dual x-ray absorptiometry, were -2.3, -1.2, +0.7, and +1.2 after treatment with placebo and 5, 20, and 40 mg alendronate, respectively. Treatment with alendronate was well tolerated and produced no fever; gastrointestinal intolerance was no more common than with placebo treatment. Short term alendronate treatment in early postmenopausal women decreased bone turnover and increased vertebral density.

Adult↗
PubMed1992

Developmental effects of methyl benzimidazolecarbamate following exposure during early pregnancy.

Methyl 2-benzimidazolecarbamate (MBC) and its parent compound benomyl are used as agricultural fungicides. Both chemicals are embryotoxic if administered during organogenesis, and benomyl is teratogenic. Based on a previous study indicating a lack of maternal effects of MBC following exposure during early pregnancy, the current experiments were designed to evaluate the effect of exposure to MBC during early pregnancy on developmental parameters of offspring. Rats were administered MBC at 0, 100, 200, 400, or 600 mg/kg/day during Days 1-8 of pregnancy and killed on Day 11 or Day 20 of gestation. On Day 11, embryos were assessed for survival rate, growth parameters, and anomalies. On Day 20, standard developmental toxicity evaluations were performed. Doses of 200 to 600 mg/kg/day MBC reduced embryonic survival by Day 11; exposure to MBC at 100 to 600 mg/kg/day reduced the number of fetuses surviving on Day 20. Evidence of developmental delay was apparent on Day 11 at all doses, and fetal weight was reduced by Day 20. MBC produced a dose-dependent increase in developmental defects seen on Day 11 and in several malformations observed on Day 20. MBC exposure during the first week of pregnancy was shown to be embryotoxic, resulting in embryonic death, growth retardation, and developmental abnormalities when evaluated on Days 11 or 20 of gestation.

Abnormalities, Drug-Induced↗
PubMed1992

Metabolic acidosis reverses the increase in serum 1,25(OH)2D in phosphorus-restricted normal men.

We tested the hypothesis that in humans, metabolic acidosis can disorder the metabolism of 1,25-dihydroxyvitamin D [1,25(OH)2D] by impairing the capacity for a sustained physiological stimulus to increase renal production of this hormone. Specifically, in seven healthy men in whom restriction of dietary phosphorus had doubled their serum concentration of 1,25(OH)2D, we induced metabolic acidosis of moderate severity with oral NH4Cl, administered for 7 days. With induction of acidosis, the serum concentration of 1,25(OH)2D decreased sharply and remained decreased and near constant throughout the period of acidosis, the decrease amounting to one-half of the increment induced by phosphorus restriction alone. The serum concentration of free 1,25(OH)2D also decreased, since the measured free fraction of 1,25(OH)2D was unaffected by NH4Cl. The decrease in serum 1,25(OH)2D was accounted for by a 16% increase in its metabolic clearance rate and by a 19% decrease in its production rate. Metabolic acidosis induced a modest increase in the concentrations of blood ionized calcium and serum phosphorus. Multiple linear regression analysis revealed that serum levels of 1,25(OH)2D varied inversely and significantly with those of plasma hydrogen ion (R = -0.77, P < 0.001), but not with those of blood ionized calcium or serum phosphorus. These data demonstrate in humans that metabolic acidosis can substantially reverse the increase in serum concentration of 1,25(OH)2D induced by phosphorus restriction. The data provide evidence that acidosis can restrict the increase in renal production and serum concentration of 1,25(OH)2D effected by a sustained physiological stimulus.

Acid-Base Equilibrium↗
PubMed1992

Progestin antagonism of estrogen stimulated 1,25-dihydroxyvitamin D levels.

Progestins are frequently used in combination with estrogen to prevent or treat postmenopausal osteoporosis. Progestins protect against the undesirable hyperplastic effects of estrogen on the endometrium. The possibility that progestins might antagonize the beneficial effects of estrogen on calcium homeostasis has received little attention. In this study we determined whether the addition of progestin to estrogen would alter the ability of estrogen to raise serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels. Women within 5 yr of menopause were treated with three cycles of oral unopposed estrogen [1 or 2 mg/day (3.67 or 7.34 mumol/day) 17 beta-estradiol (E2) for 25/30 days of each cycle] followed by three cycles of E2 plus progestin [10 mg/day (29 mumol/day) medroxyprogesterone on days 12-25]. E2 increased both total and free 1,25-(OH)2D concentrations in a dose-dependent fashion. These levels increased progressively over the three cycles of unopposed estrogen treatment. In contrast the vitamin D binding protein concentration reached maximal levels after one cycle of E2. With the addition of progestin, the levels of total and free 1,25-(OH)2D returned toward baseline although vitamin D binding protein levels remained elevated. PTH levels rose with both doses of E2 as serum calcium levels fell. Progestin did not significantly alter the effects of E2 on PTH or calcium. Our results raise the possibility that progestin may antagonize part of the salubrious effects of estrogen on calcium homeostasis.

Dihydroxycholecalciferols↗