Changes in bone mineral density over time by body mass index in the health ABC study.

UNLABELLED: Obesity appears protective against osteoporosis in cross-sectional studies. However, results from this longitudinal study found that obesity was associated with bone loss over time. Findings underscore the importance of looking at the longitudinal relationship, particularly given the increasing prevalence and duration of obesity among older adults. INTRODUCTION: Cross-sectional studies have found a positive association between body mass index (BMI) and bone mineral density (BMD), but little is known about the longitudinal relationship in US older adults. METHODS: We examined average annual rate of change in BMD by baseline BMI in the Health, Aging, and Body Composition Study. Repeated measurement of BMD was performed with dual-energy X-ray absorptiometry (DXA) at baseline and years 3, 5, 6, 8, and 10. Multivariate generalized estimating equations were used to predict mean BMD (femoral neck, total hip, and whole body) by baseline BMI (excluding underweight), adjusting for covariates. RESULTS: In the sample (n = 2570), 43 % were overweight and 24 % were obese with a mean baseline femoral neck BMD of 0.743 g/cm(2), hip BMD of 0.888 g/cm(2), and whole-body BMD of 1.09 g/cm(2). Change in total hip or whole-body BMD over time did not vary by BMI groups. However, obese older adults lost 0.003 g/cm(2) of femoral neck BMD per year more compared with normal weight older adults (p < 0.001). Femoral neck BMD change over time did not differ between the overweight and normal weight BMI groups (p = 0.74). In year 10, adjusted femoral neck BMD ranged from 0.696 g/cm(2) among obese, 0.709 g/cm(2) among normal weight, and 0.719 g/cm(2) among overweight older adults. CONCLUSIONS: Findings underscore the importance of looking at the longitudinal relationship between body composition and bone mineral density among older adults, indicating that high body mass may not be protective for bone loss over time.

Caffeine and 3-km cycling performance: Effects of mouth rinsing, genotype, and time of day.

We assessed the efficacy of caffeine mouth rinsing on 3-km cycling performance and determined whether caffeine mouth rinsing affects performance gains influenced by the CYP1A2 polymorphism. Thirty-eight recreational cyclists completed four simulated 3-km time trials (TT). Subjects ingested either 6 mg/kg BW of caffeine or placebo 1 h prior to each TT. Additionally, 25 mL of 1.14% caffeine or placebo solution were mouth rinsed before each TT. The treatments were Placebo, caffeine Ingestion, caffeine Rinse and Ingestion+Rinse. Subjects were genotyped and classified as AA homozygotes or AC heterozygotes for the rs762551 polymorphism of the CYP1A2 gene involved in caffeine metabolism. Magnitude-based inferences were used to evaluate treatment differences in mean power output based on a predetermined meaningful treatment effect of 1.0%. AC heterozygotes (4.1%) and AA homozygotes (3.4%) benefited from Ingestion+Rinse, but only AC performed better with Ingestion (6.0%). Additionally, Rinse and Ingestion+Rinse elicited better performance relative to Placebo among subjects that performed prior to 10:00 h (Early) compared with after 10:00 h (Late). The present study provides additional evidence of genotype and time of day factors that affect the ergogenic value of caffeine intake that may allow for more personalized caffeine intake strategies to maximize performance.

The effects of acute garlic supplementation on the fibrinolytic and vasoreactive response to exercise.

BACKGROUND: The purpose of this project was to examine the effects of acute garlic supplementation on fibrinolysis and vasoreactivity both at rest and following maximal exercise. METHODS: Eighteen healthy trained males (20.9 ± 2.2 years, 178 ± 7.7 cm, 75.5 ± 9.6 kg, VO2max = 59.8 ± 6.7 ml • kg(-1) • min(-1)) performed a graded treadmill test to volitional exhaustion. Blood samples were taken at rest, within two minutes post-exercise, and one hour post-exercise. Eleven of the subjects also had a brachial vasoreactivity test performed immediately after the blood sample to assess flow-mediated dilation (FMD) of the brachial artery. Participants were randomly assigned to ingest either 900 mg of powdered garlic or a placebo three hours before the exercise session. The supplement was distributed in a double-blind, crossover fashion. Participants repeated the protocol with the other treatment after a 14-day washout period. Paired t-tests were used to compare VO2max between the two trials. A two-factor (treatment and time) repeated measures analysis of variance (ANOVA) was used to assess changes in FMD, tPA activity, tPA antigen, and PAI-1 activity. A priori statistical significance was set at P <0.05. RESULTS: VO2max was greater for the garlic treatment trial vs. placebo (Placebo = 59.8 ± 6.7 ml • kg(-1) • min(-1); Garlic = 61.4 ± 6.6 ml • kg(-1) • min(-1)). There was no main effect for treatment and no treatment x time interaction for FMD or any fibrinolytic variables examined. CONCLUSION: Acute garlic supplementation does not alter vasoreactivity, fibrinolytic potential or the fibrinolytic response to exercise in young healthy trained males. Acute garlic supplementation does, however, cause a small but statistically significant increase in VO2max. It remains unclear if this increase in VO2max is of functional importance.

A phase I trial of vertical inhibition of IGF signalling using cixutumumab, an anti-IGF-1R antibody, and selumetinib, an MEK 1/2 inhibitor, in advanced solid tumours.

BACKGROUND: We completed a phase I clinical trial to test the safety and toxicity of combined treatment with cixutumumab (anti-IGF-1R antibody) and selumetinib (MEK 1/2 inhibitor). METHODS: Patients with advanced solid tumours, refractory to standard therapy received selumetinib hydrogen sulphate capsules orally twice daily, and cixutumumab intravenously on days 1 and 15 of each 28-day cycle. The study used a 3+3 design, with a dose-finding cohort followed by an expansion cohort at the maximally tolerated dose that included pharmacokinetic and pharmacodynamic correlative studies. RESULTS: Thirty patients were enrolled, with 16 in the dose-finding cohort and 14 in the expansion cohort. Grade 3 or greater toxicities included nausea and vomiting, anaemia, CVA, hypertension, hyperglycaemia, and ophthalmic symptoms. The maximally tolerated combination dose was 50 mg twice daily of selumetinib and 12 mg kg(-1) every 2 weeks of cixutumumab. Two patients achieved a partial response (one unconfirmed), including a patient with BRAF wild-type thyroid carcinoma, and a patient with squamous cell carcinoma of the tongue, and six patients achieved time to progression of >6 months, including patients with thyroid carcinoma, colorectal carcinoma, and basal cell carcinoma. Comparison of pre- and on-treatment biopsies showed significant suppression of pERK and pS6 activity with treatment. CONCLUSIONS: Our study of anti-IGF-1R antibody cixutumumab and MEK 1/2 inhibitor selumetinib showed that the combination is safe and well-tolerated at these doses, with preliminary evidence of clinical benefit and pharmacodynamic evidence of target inhibition.

The association between vitamin K status and knee osteoarthritis features in older adults: the Health, Aging and Body Composition Study.

BACKGROUND: Vitamin K-dependent (VKD) proteins, including the mineralization inhibitor matrix-gla protein (MGP), are found in joint tissues including cartilage and bone. Previous studies suggest low vitamin K status is associated with higher osteoarthritis (OA) prevalence and incidence. OBJECTIVE: To clarify what joint tissues vitamin K is relevant to in OA, we investigated the cross-sectional and longitudinal association between vitamin K status and knee OA structural features measured using magnetic resonance imaging (MRI). METHODS: Plasma phylloquinone (PK, vitamin K1) and dephosphorylated-uncarboxylated MGP ((dp)ucMGP) were measured in 791 older community-dwelling adults who had bilateral knee MRIs (mean ± SD age = 74 ± 3 y; 67% female). The adjusted odds ratios (and 95% confidence intervals) [OR (95%CI)] for presence and progression of knee OA features according to vitamin K status were calculated using marginal models with generalized estimating equations (GEEs), adjusted for age, sex, body mass index (BMI), triglycerides and other pertinent confounders. RESULTS: Longitudinally, participants with very low plasma PK (<0.2 nM) were more likely to have articular cartilage and meniscus damage progression after 3 years [OR (95% CIs): 1.7(1.0-3.0), 2.6(1.3-5.2) respectively] compared to sufficient PK (≥ 1.0 nM). Higher plasma (dp)ucMGP (reflective of lower vitamin K status) was associated with higher odds of meniscus damage, osteophytes, bone marrow lesions, and subarticular cysts cross-sectionally [ORs (95% CIs) comparing highest to lowest quartile: 1.6(1.1-2.3); 1.7(1.1-2.5); 1.9(1.3-2.8); 1.5(1.0-2.1), respectively]. CONCLUSION: Community-dwelling men and women with very low plasma PK were more likely to have progression of articular cartilage and meniscus damage. Plasma (dp)ucMGP was associated with presence of knee OA features but not progression. Future studies are needed to clarify mechanisms underlying vitamin Ks role in OA.

The effect of pulsing movements on the physiological response to common exercises.

AIM: There is a paucity of research on responses to exercises using pulsatile movements (PM) compared to using a full range of motion (FM). The purpose of the present study was to compare the physiological responses to PM vs. FM exercises. METHODS: Eight participants completed two separate exercise sessions, comprised of three sets of 20 repetitions for five different exercises. During the FM trial, all repetitions were performed using a full range of motion. In the PM trial, half of the repetitions were performed using pulsing movements. Average VO2, total VO2, HR and RPE were compared using paired t-tests. Blood lactate [La-] responses were compared using repeated measures analysis of variance. RESULTS: Average VO2 in the PM trial (1.52±0.38 L min-1) was similar to the FM trial (1.57±0.43 L min-1). However, total VO2 (PM=23.1±6.6 L, FM=27.2±6.9 L), average HR (PM=134.4 ± 10.9, FM=146.2±14.6 beats per min) and RPE (PM=12.2±0.9, FM=13.3±0.9) were significantly (P<0.05) lower for the PM trial. There were no significant differences in blood [La-] response (PM pre=1.7±0.8, post=6.1±0.8 mmol L-1; FM pre=1.6±0.4, post=6.8±0.5 mmol L-1). CONCLUSION: FM exercises elicit higher HR and RPE responses compared to PM exercises; without corresponding increases in metabolic rate.

Radical intermediates in the addition of OH to propene: photolytic precursors and angular momentum effects.

We investigate the photolytic production of two radical intermediates in the reaction of OH with propene, one from addition of the hydroxyl radical to the terminal carbon and the other from addition to the center carbon. In a collision-free environment, we photodissociate a mixture of 1-bromo-2-propanol and 2-bromo-1-propanol at 193 nm to produce these radical intermediates. The data show two primary photolytic processes occur: C-Br photofission and HBr photoelimination. Using a velocity map imaging apparatus, we measured the speed distribution of the recoiling bromine atoms, yielding the distribution of kinetic energies of the nascent C3H6OH radicals + Br. Resolving the velocity distributions of Br((2)P(1/2)) and Br((2)P(3/2)) separately with 2 + 1 REMPI allows us to determine the total (vibrational + rotational) internal energy distribution in the nascent radicals. Using an impulsive model to estimate the rotational energy imparted to the nascent C3H6OH radicals, we predict the percentage of radicals having vibrational energy above and below the lowest dissociation barrier, that to OH + propene; it accurately predicts the measured velocity distribution of the stable C3H6OH radicals. In addition, we use photofragment translational spectroscopy to detect several dissociation products of the unstable C3H6OH radicals: OH + propene, methyl + acetaldehyde, and ethyl + formaldehyde. We also use the angular momenta of the unstable radicals and the tensor of inertia of each to predict the recoil kinetic energy and angular distributions when they dissociate to OH + propene; the prediction gives an excellent fit to the data.

FGFR2 amplification has prognostic significance in gastric cancer: results from a large international multicentre study.

BACKGROUND: In preclinical gastric cancer (GC) models, FGFR2 amplification was associated with increased tumour cell proliferation and survival, and drugs targeting this pathway are now in clinical trials. METHODS: FGFR2 FISH was performed on 961 GCs from the United Kingdom, China and Korea, and the relationship with clinicopathological data and overlap with HER2 amplification were analysed. RESULTS: The prevalence of FGFR2 amplification was similar between the three cohorts (UK 7.4%, China 4.6% and Korea 4.2%), and intratumoral heterogeneity was observed in 24% of FGFR2 amplified cases. FGFR2 amplification was associated with lymph node metastases (P<0.0001). FGFR2 amplification and polysomy were associated with poor overall survival (OS) in the Korean (OS: 1.83 vs 6.17 years, P=0.0073) and UK (OS: 0.45 vs 1.9 years, P<0.0001) cohorts, and FGFR2 amplification was an independent marker of poor survival in the UK cohort (P=0.0002). Co-amplification of FGFR2 and HER2 was rare, and when high-level amplifications did co-occur these were detected in distinct areas of the tumour. CONCLUSION: A similar incidence of FGFR2 amplification was found in Asian and UK GCs and was associated with lymphatic invasion and poor prognosis. This study also shows that HER2 and FGFR2 amplifications are mostly exclusive.

Digital pattern recognition-based image analysis quantifies immune infiltrates in distinct tissue regions of colorectal cancer and identifies a metastatic phenotype.

BACKGROUND: Several studies in colorectal cancer (CRC) indicate a relationship between tumour immune infiltrates and clinical outcome. We tested the utility of a digital pattern recognition-based image analysis (DPRIA) system to segregate tissue regions and facilitate automated quantification of immune infiltrates in CRC. METHODS: Primary CRC with matched hepatic metastatic (n=7), primary CRC alone (n=18) and primary CRC with matched normal (n=40) tissue were analysed immunohistochemically. Genie pattern recognition software was used to segregate distinct tissue regions in combination with image analysis algorithms to quantify immune cells. RESULTS: Immune infiltrates were observed predominately at the invasive margin. Quantitative image analysis revealed a significant increase in the prevalence of Foxp3 (P<0.0001), CD8 (P<0.0001), CD68 (<0.0001) and CD31 (<0.0001) positive cells in the stroma of primary and metastatic CRC, compared with tumour cell mass. A direct comparison between non-metastatic primary CRC (MET-) and primary CRC that resulted in metastasis (MET+) showed an immunosuppressive phenotype, with elevated Foxp3 (P<0.05) and reduced numbers of CD8 (P<0.05) cells in the stroma of MET+ compared with MET- samples. CONCLUSION: By combining immunohistochemistry with DPRIA, we demonstrate a potential metastatic phenotype in CRC. Our study accelerates wider acceptance and use of automated systems as an adjunct to traditional histopathological techniques.

Health-related fitness and academic achievement in middle school students.

AIM: The aim of the present study was to determine the association between health-related fitness (HRF) and academic achievement in middle school youth. METHODS: Subjects were 312 middle school students. HRF was assessed using the FITNESSGRAM test battery. Students were grouped by the number of fitness tests in which they performed within the Healthy Fitness Zone, ranging from <1 test (lowest fitness) to all 5 tests (highest fitness). Academic achievement was assessed using grades (A - F) from four core classes, which were converted to interval data (A=5, F=1) and summed over the academic year and a standardized test (percentile). Maturity offset was calculated to control for the possible effect of maturity status on the association between HRF and academic achievement. Differences in academic achievement among HRF groups were determined using ANOVA. RESULTS: Grades and standardized test percentiles were higher in HRF group 5 (P<0.01) compared to HRF groups <2, 3, and 4. Cardiorespiratory endurance and muscular strength and endurance were the HRF components most strongly associated with academic achievement. CONCLUSION: HRF was related to academic achievement in youth. Students with the highest fitness level performed better on standardized tests and students with the lowest fitness level performed lower in class grades.

Modeling the rovibrationally excited C2H4OH radicals from the photodissociation of 2-bromoethanol at 193 nm.

This study photolytically generates, from 2-bromoethanol photodissociation, the 2-hydroxyethyl radical intermediate of the OH + ethene reaction and measures the velocity distribution of the stable radicals. We introduce an impulsive model to characterize the partitioning of internal energy in the C(2)H(4)OH fragment. It accounts for zero-point and thermal vibrational motion to determine the vibrational energy distribution of the nascent C(2)H(4)OH radicals and the distribution of total angular momentum, J, as a function of the total recoil kinetic energy imparted in the photodissociation. We render this system useful for the study of the subsequent dissociation of the 2-hydroxyethyl radical to the possible asymptotic channels of the OH + ethene reaction. The competition between these channels depends on the internal energy and the J distribution of the radicals. First, we use velocity map imaging to separately resolve the C(2)H(4)OH + Br((2)P(3/2)) and C(2)H(4)OH + Br((2)P(1/2)) photodissociation channels, allowing us to account for the 10.54 kcal/mol partitioned to the Br((2)P(1/2)) cofragment. We determine an improved resonance enhanced multiphoton ionization (REMPI) line strength for the Br transitions at 233.681 nm (5p (4)P(1/2) <-- 4p (2)P(3/2)) and 234.021 nm (5p (2)S(1/2) <-- 4p (2)P(1/2)) and obtain a spin-orbit branching ratio for Br((2)P(1/2)):Br((2)P(3/2)) of 0.26 +/- 0.03:1. Energy and momentum conservation give the distribution of total internal energy, rotational and vibrational, in the C(2)H(4)OH radicals. Then, using 10.5 eV photoionization, we measure the velocity distribution of the radicals that are stable to subsequent dissociation. The onset of dissociation occurs at internal energies much higher than those predicted by theoretical methods and reflects the significant amount of rotational energy imparted to the C(2)H(4)OH photofragment. Instead of estimating the mean rotational energy with an impulsive model from the equilibrium geometry of 2-bromoethanol, our model explicitly includes weighting over geometries across the quantum wave function with zero, one, and two quanta in the harmonic mode that most strongly alters the exit impact parameter. The model gives a nearly perfect prediction of the measured velocity distribution of stable radicals near the dissociation onset using a G4 prediction of the C-Br bond energy and the dissociation barrier for the OH + ethene channel calculated by Senosiain et al. (J. Phys. Chem. A 2006, 110, 6960). The model also indicates that the excited state dissociation proceeds primarily from a conformer of 2-bromoethanol that is trans across the C-C bond. We discuss the possible extensions of our model and the effect of the radical intermediate's J-distribution on the branching between the OH + ethene product channels.

Src inhibitors in early breast cancer: a methodology, feasibility and variability study.

Early clinical trials of anticancer agents may be enriched by robust biomarkers of activity. Surrogate measures used in trials of cytotoxic agents, such as tumor size regression, may not be informative when investigating targeted agents that act principally to inhibit invasion or proliferation. This study aimed to determine the validity of invasion-related biomarkers of activity for AZD0530, a potent Src inhibitor currently in clinical development. Focal adhesion kinase (FAK) and paxillin are downstream phosphorylation substrates of Src and mediate tumor cell adhesion and invasiveness. These were therefore selected as biologically relevant markers of Src inhibition. Early breast cancer was chosen as a model as multiple samples can be collected during standard treatment and there is an intervening period in which experimental intervention can be applied. Tumor tissue was collected from diagnostic core biopsies and subsequent surgical tumor excision samples in 29 women with early breast cancer attending a single center. Protein levels were assessed quantitatively by Luminex and qualitatively by immunohistochemistry. AZD0530 inhibited tumor growth in a manner independent of dose and inhibited phosphorylation of FAK and paxillin in a dose-dependent manner in a Calu-6 xenograft model. In the clinical study, agreement of within-visit and also of between-visit measurements was high and the estimated number of patients required to detect a drug effect would be low enough to allow use of these markers as endpoints in future dose selection studies.

Quantitative multiplexed quantum dot immunohistochemistry.

Quantum dots are photostable fluorescent semiconductor nanocrystals possessing wide excitation and bright narrow, symmetrical, emission spectra. These characteristics have engendered considerable interest in their application in multiplex immunohistochemistry for biomarker quantification and co-localisation in clinical samples. Robust quantitation allows biomarker validation, and there is growing need for multiplex staining due to limited quantity of clinical samples. Most reported multiplexed quantum dot staining used sequential methods that are laborious and impractical in a high-throughput setting. Problems associated with sequential multiplex staining have been investigated and a method developed using QDs conjugated to biotinylated primary antibodies, enabling simultaneous multiplex staining with three antibodies. CD34, Cytokeratin 18 and cleaved Caspase 3 were triplexed in tonsillar tissue using an 8h protocol, each localised to separate cellular compartments. This demonstrates utility of the method for biomarker measurement enabling rapid measurement of multiple co-localised biomarkers on single paraffin tissue sections, of importance for clinical trial studies.

Changes in von Willebrand factor and fibrinolysis following a post-exercise cool-down.

The purpose of this study was to determine the effect of a post-exercise active cool-down on von Willebrand factor and fibrinolysis. Ten subjects performed two maximal oxygen uptake (VO2max) tests followed by a 10-min passive (PC) or an active (AC) cool-down. Blood samples were obtained pre-exercise, post-exercise, post-PC/AC, and 1 h post-exercise and analyzed for von Willebrand factor antigen (vWf:Ag), tissue plasminogen activator (tPA) antigen and activity and plasminogen activator inhibitor-1 (PAI-1) activity. Data were analyzed using repeated measures analysis of variance. No significant differences were found between VO2max tests for treadmill time, VO2max, respiratory exchange ratio, maximal heart rate, or maximal blood lactate concentration. vWf:Ag was significantly elevated (P <0.05)following PC [198.4 (18.3)% normal] versus AC [174.5 (15.6)% normal] and remained elevated 1-h post-exercise [179.4 (16.4)% normal for PC vs 158.6 (13.8)% normal for AC]. There were no differences between tests for tPA or PAI-1 activity, although tPA antigen was significantly elevated following PC versus AC (P <0.05). Following the cool-down, hematocrit was higher (P <0.05) for the PC test [48.90 (0.36)] compared with AC [47.43 (0.51)]. An AC reduces post-exercise vWf:Ag and tPA antigen without affecting tPA or PAI-1 activity.

Appendicular fractures: a significant problem among institutionalized adults with developmental disabilities.

A high incidence of nontraumatic fracture in adults with developmental disabilities living in a state-run facility was described. Risk factors for fracture, including bone mineral density (BMD), were investigated to determine whether people at highest risk for fracture could be prospectively identified. There was a 7.3% incidence of fracture among 391 adults. Risk factors were examined for 23 residents with fracture and 23 age-, race-, and gender-matched controls. There was a trend for antiepileptic medication usage to be associated with fractures. Estimated BMD by heel ultrasound did not predict fracture; however, values were much lower than those for the general population. Fractures and low BMD are significant problems among institutionalized adults with severe developmental disabilities. Further studies to identify therapies to prevent fractures are warranted.

How much tissue is present in archival paraffin blocks and slides?

In order to inform the debate about tissue blocks and slides introduced by the Retained Organs Commission, a study is undertaken to determine the percentage weight of tissue present in the surgical archive in the cellular pathology department of a district general hospital. When original, unprocessed tissue weight is expressed as a percentage, based on the weight of 100 archival paraffin blocks, values range from 0.2% to 41.5%. When the corresponding archival slides are also included, the values fall as low as 0.1% (i.e. up to 99.9% of the stored archival material for a piece of processed tissue could be non-human material). The results are used to make a case for including archival histological material as part of the patient's clinical record, although it is accepted that this study was performed only on surgical tissue.

Human immunodeficiency virus type 1 (HIV-1) non-B subtypes are similar to HIV-1 subtype B in that coreceptor specificity is a determinant of cytopathicity in human lymphoid tissue infected ex vivo.

We sought to determine the relationship between virus-mediated CD4(+) T-lymphocyte cytopathicity and viral coreceptor preference among various human immunodeficiency virus type 1 (HIV-1) subtypes in an ex vivo-infected human lymphoid tissue model. Our data show that all R5 HIV-1 infections resulted in mild depletion of CD4(+) T lymphocytes, whereas all X4 HIV-1 infections caused severe depletion of CD4(+) T lymphocytes regardless of their subtype origin. Thus, at least for the viruses within subtypes A, B, C, and E that were tested, coreceptor specificity is a critical factor that determines the ability of HIV-1 to deplete CD4(+) T cells in human lymphoid tissue infected ex vivo.

Blood lipids in young distance runners.

PURPOSE: The purpose of this study was to examine the age-and sex-associated variation in blood lipids among young athletes. METHODS: A mixed-longitudinal design was used to examine the development of blood lipids in competitive young distance runners followed from 1982 to 1985. Serial data included 99 annual measurements for 27 male subjects and 84 annual measurements for 27 female subjects aged 9-18 yr. Total cholesterol (TC), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), and triglycerides (TG) were determined by standard procedures. RESULTS: In general, cross-sectional age group means showed that TC and LDL-C remained stable and HDL-C declined with age, especially in male subjects. TG increased with age. Age-related trends were statistically significant for HDL-C and TG in boys only (P < 0.05). TC and LDL-C were slightly greater in boys at all ages except 11, 15, and 17 yr (P > 0.05). HDL-C was similar between the sexes until 13 yr when values became greater in girls (3.2-13.8 mg.dL(-1)) (P < 0.05 in 17+ yr). No clear pattern of sex differences emerged for TG. Compared with the general population, blood lipids of young distance runners showed the following trends: 1) TC was above reference medians, 2) LDL-C tended to approximate or to be slightly above reference medians, 3) TG fluctuated about the reference medians, and 4) HDL-C was higher in distance runners compared to the reference medians before age 14 yr, but in the older age groups, especially male subjects, HDL-C either approximated or fell slightly below the reference medians. There was considerable variability in blood lipid levels among the runners. In 21 male and 18 female subjects with serial data for 3-5 yr, HDL-C declined 22.4 and 18.3 mg.dL(-1) (P < 0.05), whereas TG increased 18.0 and 14.0 mg.dL(-1)(P < 0.05 in female subjects only) in male and female subjects, respectively. Tracking coefficients over intervals of 3-5 yr were moderate to high (0.48-0.90), except for TG in male subjects (0.08). CONCLUSIONS: The results indicate that the development of blood lipids in young distance runners is similar to youth in the general population. In contrast to observations in adult endurance athletes, young distance runners did not possess a superior blood lipid profile except for HDL-C in the younger age groups.