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Biomedical subjects

K E Naylor

Publications and source records attributed to K E Naylor.

16 recordsLinked to original sources
PubMed2003

Serum osteoprotegerin as a determinant of bone metabolism in a longitudinal study of human pregnancy and lactation.

Osteoprotegerin (OPG) is a soluble decoy receptor that inhibits bone resorption by binding to receptor activator of nuclear factor kappa B ligand. Murine studies suggest that OPG is elevated in pregnancy, but its role in human pregnancy is unknown. We evaluated the relationship among OPG, bone turnover, and bone density in a longitudinal study of planned human pregnancy and lactation (n = 17; age, 20-36 yr). Samples were collected before conception; at 16, 26, and 36 wk gestation; and at 2 and 12 wk postpartum. Indexes of bone resorption included serum beta C-terminal and urinary N-terminal (uNTX) telopeptides of type I collagen. OPG increased by 110 +/- 16% (mean +/- SEM) at 36 wk (P < 0.001), followed by a rapid postpartum decline in both lactating and nonlactating women. Bone resorption was elevated at 36 wk (serum beta C-terminal telopeptides by 76 +/- 17%; urinary N-terminal telopeptides by 219 +/- 41%; P < 0.001). The tissue source of OPG in pregnancy is unknown. Human breast milk contains large amounts of OPG (162 +/- 58 ng/ml in milk vs. 0.42 +/- 0.03 ng/ml in nonpregnant serum). However, the rapid postpartum decline in serum OPG and the low serum OPG in neonates suggest a placental source. There was no correlation between change in OPG and bone turnover or bone mineral density (P > 0.05), and the physiological importance of elevated OPG in human pregnancy remains uncertain.

Adult↗
PubMed2003

The renal clearance of free and peptide-bound deoxypyridinoline: response to pamidronate treatment of Paget's disease.

Bisphosphonate treatment of Paget's disease results in a large decrease in urinary peptide-bound pyridinolines but a smaller decrease in urinary free pyridinolines. This discrepancy could be explained by changes in renal handling of pyridinoline forms. We studied eight patients with Paget's disease treated with pamidronate. We collected blood and urine at baseline and at 3 and 14 days after treatment. We measured free and total deoxypyridinoline (DPD) in serum (S) and urine (U) by high-performance liquid chromatography (HPLC). The ratio of free to total DPD at baseline was (mean +/- SE) 13 +/- 1% in serum and 37 +/- 3% in urine; at 3 days, this had increased to 25 +/- 3% in serum and 62 +/- 7% in urine. Peptide-bound (pb) DPD decreased significantly 3 days after treatment: UpbDPD -63 +/- 11%, p < 0.001; SpbDPD -51 +/- 8%, p < 0.01. Free DPD decreased in the urine after 14 days: UfDPD -48 +/- 5%, p < 0.01; there was no significant change in SfDPD. The fractional excretion of pbDPD relative to creatinine was less than one at all time-points; however, the fractional excretion of fDPD was significantly greater than one throughout the study. As a consequence, the proportion of free DPD in the urine increased as bone turnover decreased. This resulted in a smaller decrease in urine free compared with peptide-bound DPD in response to bisphosphonate therapy. Thus, the conversion of peptide-bound to free DPD in the kidney may become more efficient as bone turnover decreases as a consequence of pamidronate treatment.

Aged↗
PubMed2002

The impact of subcutaneous oestradiol implants on biochemical markers of bone turnover and bone mineral density in postmenopausal women.

OBJECTIVE: To evaluate the anabolic effect of oestrogen on bone by comparing the response of markers of bone formation (and resorption) and bone mineral density (BMD) to subcutaneous oestradiol implants. DESIGN: One year double-blind placebo controlled randomised study. SETTING: Clinical research unit within a teaching hospital. POPULATION: Twenty-one hysterectomised postmenopausal women were randomised to 25 mg oestradiol implants at baseline and at six months or to have a sham procedure at baseline and six months. METHODS: BMD and quantitative ultrasound (QUS) were assessed at baseline and one year. Bone alkaline phosphatase (bone ALP), procollagen type I N-terminal propeptide (PINP), osteocalcin (OC), free deoxypyridinoline (iFDPD), N-telopeptide of type I collagen (NTX), serum oestradiol and intact parathyroid hormone (PTH) were measured at baseline, 4, 8, 12 and 24 weeks. MAIN OUTCOME MEASURES: Percentage change markers of bone turnover and PTH and change in oestradiol levels over first six months and percentage of changes in DXA and QUS over one year. RESULTS: PINP, bone ALP and OC increased by 28%, 7% and 9%, respectively (P < 0.01) during the first four weeks of treatment and then decreased significantly. Lumbar spine (LS) and total hip (TH) BMD increased by 5.4% and 6.0% (P < 0.001), respectively, and femoral neck (FN) BMD by 3.7% (P < 0.05) during the first year of treatment compared with control subjects. The peak serum oestradiol level was achieved four weeks after implant insertion. Mean PTH levels increased significantly in subjects receiving subcutaneous oestradiol. CONCLUSION: Subcutaneous oestrogen exerted an apparent anabolic effect on bone, which was initially reflected by an increase in bone formation markers and later by a large increase in BMD.

Administration, Cutaneous↗
PubMed2001

Long-term retention of injected barium-133 in man.

Data are presented on the whole-body retention of 133Ba (half-life 10.74 y), over periods of up to 13 y after injection into six healthy male volunteers aged 25-81, and on their levels of biochemical markers for bone turnover. The results are relevant to propositions underlying the ICRP's current (Publication 67) and former (Publication 20) models of alkaline earth metabolism. The tracer was predominantly skeletal within weeks of the injection, as predicted in the current model. The mean retention accorded satisfactorily throughout with predictions based on the current model, but this accord does not necessarily validate the model, for two reasons. First, parameter values attributed to barium were influenced by data emerging during the early years of this study. Second, bone resorption rates in these subjects, as indicated by urinary markers, appear insufficient to explain the long-term reductions in skeletal retention which, in the present model, arise exclusively through this mechanism.

Adult↗
PubMed2000

The effect of pregnancy on bone density and bone turnover.

During pregnancy, the mother adapts to meet the calcium demands of the fetus. The effect of this adaptation on the maternal skeleton is not fully understood. Our objectives were to evaluate changes in bone mineral density (BMD) and bone turnover during pregnancy. We studied 16 women longitudinally, with baseline measurements before pregnancy; then at 16, 26, and 36 weeks of pregnancy; and postpartum. We measured total-body BMD and biochemical markers of bone resorption (urinary pyridinium crosslinks and telopeptides of type I collagen) and bone formation (serum bone alkaline phosphatase, propeptides of type I procollagen [PINP] and osteocalcin). We also measured parathyroid hormone (PTH), insulin-like growth factor I (IGF-I), and human placental lactogen. Postpartum, BMD increased in the arms (2.8%, P < 0.01) and legs (1.9%, P < 0.01) but decreased in the pelvis (-3.2%, P < 0.05) and spine (-4.6%, P < 0.01) compared with prepregnancy values. All biochemical markers, with the exception of osteocalcin concentration, increased during pregnancy. The change in IGF-I at 36 weeks was related to the change in biochemical markers (e.g., PINP, r = 0.72, P = 0.002). Pregnancy is a high-bone-turnover state. IGF-I levels may be an important determinant of bone turnover during pregnancy. Elevated bone turnover may explain trabecular bone loss during pregnancy.

Adult↗
PubMed1999

Bone turnover in preterm infants.

Total parenteral nutrition is associated with osteopenia in preterm infants. Insufficient calcium and phosphate are likely causes: aluminum contamination is another possible contributing factor as this adversely affects bone formation and mineralization. The study was designed to evaluate changes in biochemical markers of bone turnover in 22 preterm infants receiving total parenteral nutrition in comparison with 19 term infants. We collected urine and serum samples from 22 preterm infants, mean gestational age 29 wk, within 48 h and again at 3 wk of life. We also collected urine samples from 19 term infants, mean gestational age 39 wk, during the first day of life. Bone resorption was assessed by the measurement of urinary pyridinium cross-links by HPLC and ELISA and the N-telopeptide of type I collagen by ELISA. Bone formation was assessed in premature infants by the measurement of serum osteocalcin. The N-telopeptide of type I collagen was higher in the preterm infants compared with term at baseline (p < 0.01). There was no difference between the pyridinium cross-links in the preterm and term infants. All the biochemical markers of bone turnover increased significantly in the preterm infants during the first 3 wk of life, e.g. N-telopeptide was a 153% change from baseline (p < 0.001). Aluminum in the total parenteral nutrition solutions did not cause a decrease in bone formation at the level administered (3-6 microg, 0.1-0.2 micromol x kg(-1) x d(-1)).

Bone Diseases, Metabolic↗
PubMed1998

Adolescent health care experience of gay, lesbian, and bisexual young adults.

METHODS: Subjects were 102 self-identified gay, lesbian, and bisexual youth aged 18-23 years. A confidential self-administered survey elicited demographic information, sexual orientation information, health care experiences, subjects' understanding of medical confidentiality during ages 14-18 years, and their suggestions for improving care to gay and lesbian adolescents. RESULTS: Two-thirds of subjects never discussed sexual orientation with their provider but reported a desire to do so. Fewer than one-half of subjects remembered being informed about their right to medical confidentiality; those who reported being so informed were three times more likely to have discussed their sexual orientation with their provider. Over 70% of subjects who reported not being informed about their right to medical confidentiality stated that they would have been more likely to discuss sexual orientation with their provider had they been so informed. Only 13 of subjects had disclosed their sexual orientation to their health care providers. Of these, only half of the males received information on human immunodeficiency virus prevention. CONCLUSIONS: Health care providers may be failing to fully address issues of confidentiality and sexual orientation with adolescents, despite a decade of increased information on adolescent homosexuality.

Adolescent↗
PubMed1998

Elementary school-based health center use.

BACKGROUND: The number of school-based health centers (SBHCs) has grown from 40 in 1985 to >900 in 1996. During the 1996-1997 school year there were 914 SBHCs, 32% of which were located in elementary schools. Despite the relatively large number of elementary SBHCs in existence, SBHCs serving elementary-aged students are not adequately represented in the literature. OBJECTIVE: To analyze physical and mental primary health care utilization in a comprehensive elementary SBHC for an underserved Hispanic population. DESIGN: Retrospective analyses of services used at an elementary SBHC during the 1995-1996 school year. We describe physical and mental health services utilization provided by SBHC staff who offered a range of primary medical and mental health services. PATIENTS: The study population was predominately Hispanic, and comprised of 811 elementary school students (grades preschool through fifth) registered for SBHC use. Analyses were conducted on 591 students who used the SBHC. RESULTS: The 591 SBHC users made 2443 visits, ranging between 1 and 54 visits/individual; mean 4 visits/student. Two thirds of visits (1638) were medical provider visits, and 33% (798) were mental health provider visits. Most students (75%) saw a medical provider exclusively, 9% saw a mental health provider exclusively, and 16% of students were seen by both. Mean duration of medical provider visits +/-SD was 15 +/- 13 minutes, mean for mental health provider visits +/-SD, 37 +/- 16 minutes. Of the 3035 diagnoses, 64% were medical and 36% were mental health diagnoses. These diagnostic frequencies are grouped as follows: acute medical (31%), health maintenance (22%), depression (10%), non-Diagnostic and Statistical Manual of Mental Disorders-IV mental health diagnoses (8%), conflict disorder/emotional disturbance (8%), chronic medical (8%), academic/learning disorder (7%), anxiety disorder (3%), and other (4%). CONCLUSIONS: High rates of SBHC utilization by this population and the range of diagnoses recorded suggest health care delivered in a comprehensive, culturally-sensitive SBHC has the potential for impacting the health and well-being of underserved elementary-aged students.

Adolescent↗
PubMed1996

Comprehensive school-based health care: high school students' use of medical, mental health, and substance abuse services.

OBJECTIVES: To explore adolescent students' use of school based health and medical care and mental health and substance abuse counseling services and to compare adolescents' patterns of use of medical, mental health, and substance abuse services located in school-based and traditional settings. DESIGN: Retrospective analysis of computer-stored, standardized data for all student visits during a 4-year period. SETTING: Three high school-based student health centers. SUBJECTS: A total of 3818 adolescent students who used services provided by the school-based health centers (SBHCs). OUTCOME MEASURES: Frequencies of student visits to medical providers and mental health and substance abuse counselors and frequencies of diagnostic assignments. RESULTS: During a 38-month period, 3818 students attending senior high school made a total of 27 886 visits to three SBHCs. They represented 63% of students enrolled in the SBHCs and approximately 42% of the total school population. There were no significant demographic differences between students attending the SBHCs and the overall student body. However, compared with students who were enrolled in the SBHCs but did not use them, users were more likely to be female and Hispanic. Ninety-four percent of students using the services had visits with medical providers; 25% had visits with mental health counselors; and 8% of students had visits with substance abuse counselors. The total annual mean number of student visits was 4.7, and the annual mean numbers of visits for students who used the following services were: medical, 3.3; mental health, 5.8; and substance abuse, 6.8. An average of 1.4 diagnoses were made per visit. The most common major diagnostic categories were emotional problems (29% of all diagnoses), health supervision (13%), respiratory problems (11%), reproductive health problems (11%), and substance abuse problems (8%). Almost one fourth of the students had contact with more than one of the three categories of service provicer. Visit frequency increased significantly for students who used two categories of provider (13 to 15 mean total visits compared with 4 to 5 mean total visits for students who used just one category of provider) and escalated to a mean of 32 total visits if all three categories of service were used. CONCLUSIONS: Adolescents attending SBHCs had higher rates of visits for health and medical care than adolescents using traditional sources of medical care. The proportions of student users of SBHC mental health and substance abuse counseling services were commensurate with the estimated prevalences of these problems in this country's adolescent population. In addition, the mean numbers of visits to mental health counselors in SBHCs compared favorably with adolescent visit rates for mental health services in other settings. Too little information is available about adolescent use of substance abuse services in non-school-based settings to make similar comparisons. In summary, adolescent users of SBHCs seemed to have a higher use of medical, mental health, and probably substance abuse counseling services than did adolescents in the general populations. These findings are consistent with the interpretation that SBHCs do enhance adolescents' access to care for medical, mental health, and substance abuse problems.

Adolescent↗
PubMed1995

Histomorphometric and biochemical characterization of bone following acute severe burns in children.

Severe burns in adults is associated with an uncoupling of normal remodeling, low bone formation without reduced resorption. The risk of osteopenia that may occur under such circumstances is heightened by our detection in a cross-sectional study of low bone mass in severely burned children. We report here the acute histomorphometric and biochemical response of bone to severe burn injury, as well as bone mass in severely burned children. We enrolled 24 patients ages 5.8 to 17.5 years following burns of 63 +/- 16% (SD) body surface area. Serum and urine were collected weekly until iliac crest bone biopsy was obtained 26 +/- 10 days postburn. Seventeen of 18 patients, including 5 patients receiving growth hormone treatment to accelerate wound healing, failed to take up doxycycline in trabecular bone, and had no detectable osteoblasts at the osteoid seam, while eroded surface was normal and osteoblasts were documented by staining. Thus, bone formation was virtually absent. There was an eightfold elevation in urinary free cortisol excretion and high serum levels of acute phase reactants and interleukin-1 beta and -6. Biochemical markers of bone formation, osteocalcin, and type I procollagen propeptide were low, as were resorptive markers urinary pyridinoline and deoxypyridinoline. However, there was no correlation with resorptive surface. Mean age-related z-score for bone mass was -1.06 +/- 1.05, 40 days postburn. Immobilization and endogenous corticosteroid production may be the main factors responsible for acutely reduced bone formation while inflammatory cytokines may mediate resorption.

Absorptiometry, Photon↗
PubMed1995

Student opinions of condom distribution at a Denver, Colorado, high school.

Over the past two decades, the reported number of women and men who have had intercourse by age 18 has increased by approximately 20%. Concomitant increases occurred in the incidence of teen-age pregnancies and sexually transmitted diseases (STDs), including HIV. Increasing condom availability within schools has been proposed as one means of preventing the serious potential consequences of unprotected sexual intercourse. Although published surveys report 68% to 75% of adults have supported distributing condoms in schools, little is known about what students think about making condoms available at school. In this survey, high school students in Denver initiated and helped conduct a school-wide survey to assess student opinions about condom distribution in their school. Of 931 high school students responding to the survey, 85% replied that condoms should be distributed in their school, and 76% believed making condoms more accessible would not change the frequency of sexual activity among teens.

Adolescent↗
PubMed1995

Different responses of biochemical markers of bone resorption to bisphosphonate therapy in Paget disease.

We examined the response of different biochemical markers of bone resorption to bisphosphonate therapy (400 mg of etidronate daily for 6 months) in mild Paget disease (n = 14). Urinary markers included hydroxyproline (OHP), total (T) and free (F) pyridinolines (Pyds) determined by HPLC, immunoreactive FPyds, immunoreactive TPyds, and the N- and C-terminal telopeptides of type I collage (NTx, CL). Serum measurements included tartrate-resistant acid phosphatase (TRAcP) and the C-terminal telopeptide of type I collagen (ICTP). ICTP and TRAcP showed a minimal response to therapy (% change at 6 months, -13.1 +/- 6.8 and -6.7 +/- 3.4, respectively). The response was greatest for urinary telopeptides (NTx and CL; % change -75.7 +/- 7.5 and -73.4 +/- 8.9, respectively). The response was somewhat greater for TPyds than for FPyds. We conclude that: (a) ICTP and TRAcP are unreliable indicators of changes in bone turnover; (b) oligopeptide-bound Pyds and telopeptide fragments of type I collagen in urine show a somewhat greater response to therapy than do FPyds and may be more sensitive indicators of bone resorption; and (c) as yet no evidence suggests that these markers are substantially better predictors of the clinical response to therapy than serum total alkaline phosphatase or urinary OHP. There are several problems with the interpretation of these measurements in Paget disease, and the clinical utility of these measurements remains uncertain.

Acid Phosphatase↗
PubMed1979

The binding of [3H]-oestradiol-17 beta in the immature rat uterus during the sequential administration of non-steroidal anti-oestrogens.

1 The binding of [(3)H]-oestradiol-17beta (0.08 mug) in the uterus, vagina, liver and heart of immature female rats has been studied in vivo and the effect of daily administrations of the non-steroidal anti-oestrogens, tamoxifen and monohydroxytamoxifen, on the 2 h accumulation of [(3)H]-oestradiol-17beta in the uterus has been determined.2 Doses of tamoxifen (8 mug daily) or monohydroxytamoxifen (1.28 mug daily), which have previously been found to antagonize completely the uterotrophic activity of oestradiol-17beta (0.08 mug daily), did not significantly reduce the total uterine binding of 0.08 mug [(3)H]-oestradiol-17beta administered on day 4 of a 3-day uterine weight test.3 The simultaneous administration of tamoxifen (8 mug) or monohydroxytamoxifen (1.28 mug) with [(3)H]-oestradiol-17beta (0.08 mug) on day 3 of a uterine weight test did not significantly reduce the total uterine binding of oestradiol-17beta. The binding of [(3)H]-oestradiol-17beta was reduced if monohydroxytamoxifen or tamoxifen was administered 4 h before the oestradiol.4 Tamoxifen (8 mug daily) or monohydroxytamoxifen (1.28 mug daily) did not prevent the translocation of [(3)H]-oestradiol (0.08 mug) to the uterine cell nucleus on day 3 of a 3-day uterine weight test.5 The measurement of total nuclear oestrogen receptors by an exchange assay technique demonstrated a higher concentration of oestrogen receptors in anti-oestrogen-treated animals compared with controls.6 Since the administration of anti-oestrogenic doses of non-steroidal anti-oestrogens during a 3-day uterine weight test did not inhibit the total binding of oestradiol in the uterus, or affect the translocation of the steroid to the nucleus, the mechanism of action of non-steroidal anti-oestrogens over the range of the partial agonist dose-response curve must involve an interaction, or competition of oestradiol-17beta- and anti-oestrogen-oestrogen receptor complexes for sites within the nucleus.

Animals↗
PubMedDate not supplied

Nonsteroidal antiestrogens: their biological effects and potential mechanisms of action.

The uterotropic and antiuterotrapic effects of a variety of structural derivatives of the nonsteroidal antiestrogen tamoxifen have been determined in the rat and the mouse. One derivative, monohydroxytamoxifen, was found to be a potent antiestrogen in the rat, with a high affinity for the estrogen receptor. Various techniques of sucrose density gradient analysis were used to demonstrate that estradiol and tamoxifen bind to the rat uterine cytoplasmic estrogen receptor. Estrogens and antiestrogens provoke the translocation of estrogen receptors to the nucleus and deplete the cytoplasmic estrogen receptor pool for short or long periods depending on the dose administered. Estradiol stimulates endometrial hyperplasia with an increase in total uterine DNA content, whereas tamoxifen stimulates endometrial hypertrophy with only a slight increase in uterine DNA content. It is concluded that the molecular shape of the ligand that binds to the estrogen receptor determines antiestrogenic activity.

Animals↗