bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence of Anterior Cruciate Ligament Injuries among Elite Ballet and Modern Dancers
Authors: Liederbach Marijeanne , Dilgen Faye E. , Rose Donald J.
Published: August 2008

Background

Ballet and modern dance are jump-intensive activities, but little is known about the incidence of anterior cruciate ligament (ACL) injuries among dancers.

Hypothesis

Rigorous jump and balance training has been shown in some prospective studies to significantly reduce ACL injury rates among athletes. Dancers advance to the professional level only after having achieved virtuosic jump and balance technique. Therefore, dancers on the elite level may be at relatively low risk for ACL injury.

Study Design

Descriptive epidemiology study.

Methods

Dance exposure, injuries, and injury conditions were systematically recorded at 4 dance organizations over 5 years. Select neuromuscular and psychometric variables were compared between and within ACL-injured and noninjured dancers.

Results

Of 298 dancers, 12 experienced an ACL injury over the 5-year period. The incidence of ACL injury was 0.009 per 1000 exposures. Landing from a jump onto 1 leg was the mechanism of injury in 92% of cases. Incidence was not statistically different between gender or dance groups, although women modern dancers had a 3 to 5 times greater relative risk than women ballet dancers and men dancers. No difference between ACL-injured and noninjured dancers emerged with regard to race, oral contraceptive use, or select musculoskeletal measures.

Conclusion

Dancers suffer considerably fewer ACL injuries than athletes participating in team ball sports. The training dancers undertake to perfect lower extremity alignment, jump, and balance skills may serve to protect them against ACL injury. Anterior cruciate ligament injuries happened most often late in the day and season, suggesting an effect of fatigue.
The Influence of Religiosity, Gender, and Language Preference Acculturation on Sexual Activity Among Latino/a Adolescents
Authors: Edwards Lisa M. , Fehring Richard J. , Jarrett Keyona M. , Haglund Kristin A.
Published: August 2008

The purpose of this study was to determine the main and interactive effects of religiosity, gender, and language preference acculturation on sexual activity among 570 Latino/a adolescents from the 2002 National Survey of Family Growth. Results indicated that adolescents who viewed religion as very important, had frequent church attendance, and had more traditional attitudes on sexuality were less likely ever to have sex compared with adolescents who were less religious. Those with frequent church attendance and high traditional attitudes had fewer lifetime and recent sex partners. Unassimilated religious youth were less likely ever to have sex, had fewer lifetime and recent sexual partners, and a later age of sexual debut. Females were less likely to have had sex, had fewer recent and lifetime partners, and had a later age of coital debut than males. Religiosity had a healthy dampening of sexual activity among Latino/a adolescents and, in particular, among those who were less assimilated.
Pitfalls Associated With Antibiograms
Authors: Eiland Edward H. , Dunne Christopher Ryan , Lindgren William
Published: August 2008

An accurate, appropriately collated antibiogram represents an integral resource for health care providers when assessing bacterial resistance and guiding antimicrobial selection and formulary decisions. Interpretation of bacterial susceptibility statistics is problematic yet frequent and unrecognized pitfalls may be avoided by following the M39-A2 guidelines to ensure correct analysis and presentation of cumulative antimicrobial susceptibility test data. This review addresses guideline recommendations related to antibiogram development, CLSI breakpoint interpretation, antimicrobial inclusion decisions, and the avoidance of duplicate and surveillance isolates. Unit-specific antibiograms in critical care units is encouraged for differentiation between hospital-wide ecology and these specific areas harboring more resistant pathogens. Antibiograms cannot track the emergence of microbial resistance during therapy and discrepancies exist between automated microbiology surveillance systems and their agreement with manual surveillance methods. When striving to improve overall patient outcomes, the use of a well-produced and disseminated antibiogram helps guide clinical decision making for patients requiring antimicrobial therapy.
Imperfect Information and Contagion in Capital Markets
Authors: Dupuy Philippe
Published: August 2008

In this article, we test the importance of the role played by imperfect information in emerging markets sovereign bonds. We develop a model of secondary market bond spreads that incorporates measures of both risk and ambiguity created by imperfect information. We test it on a large set of emerging markets over a recent period by using bid and ask spreads as a proxy for the level of ambiguity in each market. We find strong evidence that ambiguity is a key element in sovereign spread determination in secondary markets. We also show that the concept of ambiguity is a good candidate for justifying contagion during a crisis. In particular, we are able to discriminate between crises that arose due to a global disturbance on perceived ambiguity from others.
Bond Market Emergence
Authors: Hanousek Jan , Kočenda Evžen , Zemčík Petr
Published: August 2008

We analyse the emerging Serbian bond market to compare its behaviour to developed markets and to indicate what is behind bond market emergence. As an analytical tool we model the term structure of the bond market. We find that a modified standard model performs rather well in the environment of an emerging market with numerous imperfections and external shocks involved since we obtain a concave yield curve as in developed markets. Further, we show the link of such a structure to macroeconomic developments in terms of responsiveness of interest rates to changes in industrial production and inflation. Finally, the frequency of trading, market liquidity and transparency can be considered as drivers that make the market emerge.
Relationships Between Game Attributes and Learning Outcomes
Authors: Wilson Katherine A. , Bedwell Wendy L. , Lazzara Elizabeth H. , Salas Eduardo , Burke C. Shawn , Estock Jamie L. , Orvis Kara L. , Conkey Curtis
Published: August 2008

Games are an effective and cost-saving method in education and training. Although much is known about games and learning in general, little is known about what components of these games (i.e., game attributes) influence learning outcomes. The purpose of this article is threefold. First, we review the literature to understand the “state of play” in the literature in regards to learning outcomes and game attributes—what is being studied. Second, we seek out what specific game attributes have an impact on learning outcomes. Finally, where gaps in the research exist, we develop a number of theoretically based proposals to guide further research in this area.
Health Literacy and Health Actions: A Review and a Framework From Health Psychology
Authors: von Wagner Christian , Steptoe Andrew , Wolf Michael S. , Wardle Jane
Published: August 2008

The association between performance on health literacy measures and health outcomes is well established. The next step is to understand the processes through which health literacy affects health. This review introduces a framework drawing on ideas from health psychology and proposing that associations between health literacy and health outcomes could be mediated by a range of health actions involving access and use of health care, patient—provider interactions, and the management of health and illness. The framework outlines routes through which health literacy might affect either health actions themselves or the motivational and volitional determinants that have been identified in social cognition models. The implications of the framework for future research and intervention strategies are discussed.
Expression of angiotensin-converting enzyme (CD143) identifies and regulates primitive hemangioblasts derived from human pluripotent stem cells
Authors: Zambidis Elias T. , Soon Park Tea , Yu Wayne , Tam Ada , Levine Michal , Yuan Xuan , Pryzhkova Marina , Péault Bruno
Published: August 2008

We report that angiotensin-converting enzyme (ACE), a critical physiologic regulator of blood pressure, angiogenesis, and inflammation, is a novel marker for identifying hemangioblasts differentiating from human embryonic stem cells (hESC). We demonstrate that ACE+CD45−CD34+/− hemangioblasts are common yolk sac (YS)–like progenitors for not only endothelium but also both primitive and definitive human lymphohematopoietic cells. Thrombopoietin and basic fibroblast growth factor are identified as critical factors for the proliferation of human hemangioblasts. The developmental sequence of human embryoid body hematopoiesis is remarkably congruent to the timeline of normal human YS development, which occurs during weeks 2 to 6 of human gestation. Furthermore, ACE and the renin-angiotensin system (RAS) directly regulate hemangioblast expansion and differentiation via signaling through the angiotensin II receptors AGTR1 and AGTR2. ACE enzymatic activity is required for hemangioblast expansion, and differentiation toward either endothelium or multipotent hematopoietic progenitors is dramatically augmented after manipulation of angiotensin II signaling with either AGTR1- or AGTR2-specific inhibitors. The RAS can therefore be exploited to direct the hematopoietic or endothelial fate of hESC-derived hemangioblasts, thus providing novel opportunities for human tissue engineering. Moreover, the initial events of human hematoendotheliogenesis can be delineated in a manner previously impossible because of inaccessibility to early human embryonic tissues.
Clinical and immunologic consequences of a somatic reversion in a patient with X-linked severe combined immunodeficiency
Authors: Speckmann Carsten , Pannicke Ulrich , Wiech Elisabeth , Schwarz Klaus , Fisch Paul , Friedrich Wilhelm , Niehues Tim , Gilmour Kimberly , Buiting Karin , Schlesier Michael , Eibel Hermann , Rohr Jan , Superti-Furga Andrea , Groß-Wieltsch Ute , Ehl Stephan
Published: August 2008

X-linked severe combined immunodeficiency is a life-threatening disorder caused by mutations in the gene encoding the interleukin-2 receptor gamma chain (IL2RG). Hypomorphic mutations and reversion of mutations in subpopulations of cells can result in variant clinical phenotypes, making diagnosis and treatment difficult. We describe a 5-year-old boy with mild susceptibility to infection who was investigated for a mutation in IL2RG due to persistent natural killer (NK)– and T-cell lymphopenia. A functionally relevant novel T466C point mutation was found in B, NK, and epithelial cells, whereas α/β and γ/δ T cells showed the normal gene sequence, suggesting reversion of the mutation in a common T-cell precursor. This genetic correction in T cells resulted in a diverse T-cell repertoire and significant immunity despite failure to produce specific antibodies linked to an intrinsic defect of mutant B cells. These observations confirm the potential of revertant T-cell precursors to reconstitute immune function, but questions remain on the longevity of revertant cells implicating the need for careful follow up and early consideration of hematopoietic stem cell transplantation (HSCT).
Bioelectrical impedance phase angle as a prognostic indicator in breast cancer
Authors: Gupta Digant , Lammersfeld Carolyn A , Vashi Pankaj G , King Jessica , Dahlk Sadie L , Grutsch James F , Lis Christopher G
Published: August 2008

Background

Bioelectrical impedance analysis (BIA) is an easy-to-use, non-invasive, and reproducible technique to evaluate changes in body composition and nutritional status. Phase angle, determined by bioelectrical impedance analysis (BIA), detects changes in tissue electrical properties and has been hypothesized to be a marker of malnutrition. Since malnutrition can be found in patients with breast cancer, we investigated the prognostic role of phase angle in breast cancer.

Methods

We evaluated a case series of 259 histologically confirmed breast cancer patients treated at Cancer Treatment Centers of America. Kaplan Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of phase angle independent of stage at diagnosis and prior treatment history. Survival was calculated as the time interval between the date of first patient visit to the hospital and the date of death from any cause or date of last contact/last known to be alive.

Results

Of 259 patients, 81 were newly diagnosed at our hospital while 178 had received prior treatment elsewhere. 56 had stage I disease at diagnosis, 110 had stage II, 46 had stage III and 34 had stage IV. The median age at diagnosis was 49 years (range 25 – 74 years). The median phase angle score was 5.6 (range = 1.5 – 8.9). Patients with phase angle <= 5.6 had a median survival of 23.1 months (95% CI: 14.2 to 31.9; n = 129), while those > 5.6 had 49.9 months (95% CI: 35.6 to 77.8; n = 130); the difference being statistically significant (p = 0.031). Multivariate Cox modeling, after adjusting for stage at diagnosis and prior treatment history found that every one unit increase in phase angle score was associated with a relative risk of 0.82 (95% CI: 0.68 to 0.99, P = 0.041). Stage at diagnosis (p = 0.006) and prior treatment history (p = 0.001) were also predictive of survival independent of each other and phase angle.

Conclusion

This study demonstrates that BIA-derived phase angle is an independent prognostic indicator in patients with breast cancer. Nutritional interventions targeted at improving phase angle could potentially lead to an improved survival in patients with breast cancer.
Osteoid osteoma of a metacarpal bone: A case report and review of the literature
Authors: Chronopoulos Efstathios , Xypnitos Fragiskos N , Nikolaou Vassilios S , Efstathopoulos Nicolas , Korres Dimitrios
Published: August 2008

Introduction

Osteoid osteoma is a benign tumor of the growing skeleton. It presents with pain, which is usually worse at night. The radiographic features consist of a central oval or round nidus surrounded first by a radiolucent area followed by another area of sclerotic bone. In the hand, osteoid osteoma is more commonly located in the phalanges and carpal bones. The metacarpals are the least common sites for osteoid osteoma.

Case presentation

We present a case of an osteoid osteoma of the left third metacarpal bone in a 36-year-old woman. The clinical and radiographic findings along with the surgical management of the lesion are presented. The pain disappeared immediately after the operation. At the 2-year follow-up, the patient was pain-free and there was no evidence of recurrence.

Conclusion

Physicians should be aware of the unusual presence and the atypical clinical presentation of this benign lesion in the metacarpal bones of the hand.
Allergic enterocolitis and protein-losing enteropathy as the presentations of manganese leak from an ingested disk battery: A case report
Authors: Altaf Muhammad A , Goday Praveen S , Telega Grzegorz
Published: August 2008

Introduction

Disk battery ingestions can lead to serious complications including airway or digestive tract perforation, blood vessel erosions, mediastinitis, and stricture formation.

Case presentation

We report a 20-month-old Caucasian child who developed eosinophilic enterocolitis and subsequent protein-losing enteropathy from manganese that leaked from a lithium disk battery. The disk battery was impacted in her esophagus for 10 days resulting in battery corrosion. We postulate that this patient's symptoms were due to a manganese leak from the 'retained' disk battery; this resulted in an allergic response in her gut and protein-losing enteropathy. Her symptoms improved gradually over the next 2 weeks with conservative management.

Conclusion

This is the first case report to highlight the potential complication of allergic enterocolitis and protein-losing enteropathy secondary to ingested manganese. Clinicians should be vigilant about this rare complication in managing patients with disk battery ingestions.
Novel human neutrophil agonistic properties of arsenic trioxide: involvement of p38 mitogen-activated protein kinase and/orc-junNH2-terminal MAPK but not extracellular signal-regulated kinases-1/2
Authors: Binet François , Girard Denis
Published: August 2008

Arsenic trioxide (ATO) is known for treating acute promyelocytic leukemia and for inducing apoptosis and mitogen-activated protein kinases (MAPKs) in promyelocytes and cancer cells. We recently reported that ATO induces neutrophil apoptosis. The aim of this study was to establish whether or not ATO recruits MAPKs in neutrophils, as well as to further investigate its agonistic properties. We found that ATO activates p38 and that, unlike H2O2, this response was not inhibited by exogenous catalase. Also, we demonstrated that ATO-induced p38 activation occurs before H2O2 generation and without a calcium burst. We next established that ATO recruits c-jun NH2-terminal (JNK) but not extracellular signal-regulated kinase 1 and 2 (Erk-1/2). Using pharmacological inhibitors, we found that the proapoptotic activity of ATO occurs by a MAPK-independent mechanism. In contrast, the ability of ATO to enhance adhesion, migration, phagocytosis, release, and activity of gelatinase and degranulation of secretory, specific, and gelatinase, but not azurophilic granules, is dependent upon activation of p38 and/or JNK. This is the first study establishing that ATO possesses important agonistic properties in human neutrophils. Given the central role of neutrophils in various inflammatory disorders, we propose that ATO might have broader therapeutic implications in clinics, especially for regulating inflammation.
Thyroid Hormones Directly Alter Human Hair Follicle Functions: Anagen Prolongation and Stimulation of Both Hair Matrix Keratinocyte Proliferation and Hair Pigmentation
Authors: van Beek Nina , Bodó Enikő , Kromminga Arno , Gáspár Erzsébet , Meyer Katja , Zmijewski Michal A. , Slominski Andrzej , Wenzel Björn E. , Paus Ralf
Published: August 2008

Context: Both insufficient and excess levels of thyroid hormones (T3 and T4) can result in altered hair/skin structure and function (e.g. effluvium). However, it is still unclear whether T3 and T4 exert any direct effects on human hair follicles (HFs), and if so, how exactly human HFs respond to T3/T4 stimulation.

Objective: Our objective was to asses the impact of T3/T4 on human HF in vitro.

Methods: Human anagen HFs were isolated from skin obtained from females undergoing facelift surgery. HFs from euthyroid females between 40 and 69 yr (average, 56 yr) were cultured and treated with T3/T4.

Results: Studying microdissected, organ-cultured normal human scalp HFs, we show here that T4 up-regulates the proliferation of hair matrix keratinocytes, whereas their apoptosis is down-regulated by T3 and T4. T4 also prolongs the duration of the hair growth phase (anagen) in vitro, possibly due to the down-regulation of TGF-β2, the key anagen-inhibitory growth factor. Because we show here that human HFs transcribe deiodinase genes (D2 and D3), they may be capable of converting T4 to T3. Intrafollicular immunoreactivity for the recognized thyroid hormone-responsive keratins cytokeratin (CK) 6 and CK14 is significantly modulated by T3 and T4 (CK6 is enhanced, CK14 down-regulated). Both T3 and T4 also significantly stimulate intrafollicular melanin synthesis.

Conclusions: Thus, we present the first evidence that human HFs are direct targets of thyroid hormones and demonstrate that T3 and/or T4 modulate multiple hair biology parameters, ranging from HF cycling to pigmentation.
Relations between Endogenous Androgens and Estrogens in Postmenopausal Women with Suspected Ischemic Heart Disease
Authors: Braunstein Glenn D. , Johnson B. Delia , Stanczyk Frank Z. , Bittner Vera , Berga Sarah L. , Shaw Leslee , Hodgson T. Keta , Paul-Labrador Maura , Azziz Ricardo , Merz C. Noel Bairey
Published: August 2008

Context: Because androgens are obligatory precursors of estrogens, it is reasonable to assume that their serum concentrations would exhibit positive correlations. If so, then epidemiologic studies that examine the association between androgens and pathological processes should adjust the results for the independent effect of estrogens.

Objective: The objective of the study was to examine the interrelationships among testosterone (T), androstenedione, estradiol (E2), estrone, and SHBG in postmenopausal women.

Design: This was a cross-sectional study of women participating in the National Heart, Blood, and Lung Institute-sponsored Women’s Ischemia Syndrome Evaluation study.

Setting: The study was conducted at four academic medical centers.

Patients: A total of 284 postmenopausal women with chest pain symptoms or suspected myocardial ischemia.

Main Outcome Measures: Post hoc analysis of the relationships among sex steroid hormones with insulin resistance, body mass index (BMI), and presence or absence of coronary artery disease as determined by coronary angiography.

Results: BMI was significantly associated with insulin resistance, total E2, free E2, bioavailable E2, and free T. Highly significant correlations were found for total T, free T, and androstenedione with total E2, free E2, bioavailable E2, and estrone and persisted after adjustment for BMI and insulin resistance. A significant relationship was present between total and free T and the presence of coronary artery disease after adjustment for the effect of E2.

Conclusions: Serum levels of androgens and estrogens track closely in postmenopausal women referred for coronary angiography for suspected myocardial ischemia. Epidemiological studies that relate sex steroid hormones to physiological or pathological processes need to control for the independent effect of both estrogens and androgens.
Severe Intrauterine Growth Retardation and Atypical Diabetes Associated with a Translocation Breakpoint Disrupting Regulation of the Insulin-Like Growth Factor 2 Gene
Authors: Murphy R. , Baptista J. , Holly J. , Umpleby A. M. , Ellard S. , Harries L. W. , Crolla J. , Cundy T. , Hattersley A. T.
Published: August 2008

Context: IGF-II is an imprinted gene (predominantly transcribed from the paternally inherited allele), which has an important role in fetal growth in mice. IGF2 gene expression is regulated by a complex system of enhancers and promoters that determine tissue-specific and development-specific transcription. In mice, enhancers of the IGF2 gene are located up to 260 kb telomeric to the gene. The role of IGF-II in humans is unclear.

Objective: A woman of short adult stature (1.46 m, −3 sd score) born with severe intrauterine growth retardation (1.25 kg at term, −5.4 sd score) and atypical diabetes diagnosed at the age of 23 yr had a balanced chromosomal translocation t(1;11) (p36.22; p15.5). We hypothesized that her phenotype resulted from disruption of her paternally derived IGF2 gene because her daughter who inherited the identical translocation had normal birth weight.

Design: Both chromosomal break points were identified using fluorescent in situ hybridization. Sequence, methylation, and expression of the IGF2 gene was examined. Hyperinsulinemic, euglycemic clamp with glucose tracers and magnetic resonance imaging of the thorax, abdomen, and pelvis were performed.

Results: The 11p15.5 break point mapped 184 kb telomeric of the IGF2 gene. Microsatellite markers confirmed paternal origin of this chromosome. IGF2 gene sequence and methylation was normal. IGF2 gene expression was reduced in lymphoblasts. Clamp studies showed marked hepatic and total insulin resistance. Massive excess sc fat was seen on magnetic resonance imaging despite slim body mass index (21.1 kg/m2).

Conclusions: A break point 184 kb upstream of the paternally derived IGF2 gene, separating it from some telomeric enhancers, resulted in reduced expression in some mesoderm-derived adult tissues causing intrauterine growth retardation, short stature, lactation failure, and insulin resistance with altered fat distribution.
Autoantibodies against Type I Interferons as an Additional Diagnostic Criterion for Autoimmune Polyendocrine Syndrome Type I
Authors: Meloni Antonella , Furcas Maria , Cetani Filomena , Marcocci Claudio , Falorni Alberto , Perniola Roberto , Pura Mikuláš , Bøe Wolff Anette S. , Husebye Eystein S. , Lilic Desa , Ryan Kelli R. , Gennery Andrew R. , Cant Andrew J. , Abinun Mario , Spickett Gavin P. , Arkwright Peter D. , Denning David , Costigan Colm , Dominguez Maria , McConnell Vivienne , Willcox Nick , Meager Anthony
Published: August 2008

Context: In autoimmune polyendocrinopathy syndrome type I (APS-I), mutations in the autoimmune regulator gene (AIRE) impair thymic self-tolerance induction in developing T cells. The ensuing autoimmunity particularly targets ectodermal and endocrine tissues, but chronic candidiasis usually comes first. We recently reported apparently APS-I-specific high-titer neutralizing autoantibodies against type I interferons in 100% of Finnish and Norwegian patients, mainly with two prevalent AIRE truncations.

Objectives: Because variability in clinical features and age at onset in APS-I frequently results in unusual presentations, we prospectively checked the diagnostic potential of anti-interferon antibodies in additional APS-I panels with other truncations or rare missense mutations and in disease controls with chronic mucocutaneous candidiasis (CMC) but without either common AIRE mutation.

Design: The study was designed to detect autoantibodies against interferon-α2 and interferon-ω in antiviral neutralization assays.

Setting and Patients: Patients included 14 British/Irish, 15 Sardinian, and 10 Southern Italian AIRE-mutant patients with APS-I; also 19 other patients with CMC, including four families with cosegregating thyroid autoimmunity.

Outcome: The diagnostic value of anti-interferon autoantibodies was assessed.

Results: We found antibodies against interferon-α2 and/or interferon-ω in all 39 APS-I patients vs. zero of 48 unaffected relatives and zero of 19 British/Irish CMC patients. Especially against interferon-ω, titers were nearly always high, regardless of the exact APS-I phenotype/duration or AIRE genotype, including 12 different AIRE length variants or 10 point substitutions overall (n = 174 total). Strikingly, in one family with few typical APS-I features, these antibodies cosegregated over three generations with autoimmune hypothyroidism plus a dominant-negative G228W AIRE substitution.

Conclusions: Otherwise restricted to patients with thymoma and/or myasthenia gravis, these precocious persistent antibodies show 98% or higher sensitivity and APS-I specificity and are thus a simpler diagnostic option than detecting AIRE mutations.
Estradiol Supplementation in Postmenopausal Women Attenuates Suppression of Pulsatile Growth Hormone Secretion by Recombinant Human Insulin-like Growth Factor Type I
Authors: Veldhuis Johannes D. , Keenan Daniel M. , Bailey Joy N. , Adeniji Adenborduin , Miles John M. , Paulo Remberto , Cosma Mihaela , Soares-Welch Cacia
Published: August 2008

Background: Why pulsatile GH secretion declines in estrogen-deficient postmenopausal individuals remains unknown. One possibility is that estrogen not only enhances stimulation by secretagogues but also attenuates negative feedback by systemic IGF-I.

Site: The study took place at an academic medical center.

Subjects: Subjects were healthy postmenopausal women (n = 25).

Methods: The study included randomized assignment to estradiol (n = 13) or placebo (n = 12) administration for 16 d and randomly ordered administration of 0, 1.0, 1.5, and 2.0 mg/m2 recombinant human IGF-I sc on separate days fasting.

Analysis: Deconvolution analysis of pulsatile and basal GH secretion and approximate entropy (pattern-regularity) analysis were done to quantify feedback effects of IGF-I.

Outcomes: Recombinant human IGF-I injections increased mean and peak serum IGF-I concentrations dose dependently (P < 0.001) and suppressed mean GH concentrations (P < 0.001), pulsatile GH secretion (P = 0.001), and approximate entropy (P < 0.001). Decreased GH secretion was due to reduced secretory-burst mass (P = 0.005) and frequency (P < 0.001) but not basal GH release (P = 0.52). Estradiol supplementation lowered endogenous, but did not alter infused, IGF-I concentrations while elevating mean GH concentrations (P = 0.012) and stimulating pulsatile (P = 0.008) and basal (P < 0.001) GH secretion. Estrogen attenuated IGF-I’s inhibition of pulsatile GH secretion (P = 0.042) but was unable to restore physiological GH pulse frequency or normalize approximate entropy.

Conclusion: Short-term estrogen replacement in postmenopausal women selectively mutes IGF-I-mediated feedback on pulsatile GH secretion. Disinhibition of negative feedback thus confers a novel mechanism by which estrogen may obviate hyposomatotropism.
Fetuin-A and Its Relation to Metabolic Syndrome and Fatty Liver Disease in Obese Children Before and After Weight Loss
Authors: Reinehr Thomas , Roth Christian L.
Published: August 2008

Context: There are very limited data available concerning the relationships between fetuin-A, weight status, nonalcoholic fatty liver disease (NAFLD), and features of the metabolic syndrome (MetS) in obese humans, and especially in children.

Objective: Our objective was to study the longitudinal relationships between fetuin-A, NAFLD, and MetS in obese children.

Design: This was a 1-yr longitudinal follow-up study.

Setting: This study was performed in primary care.

Patients: A total of 36 obese and 14 lean children was included in the study.

Intervention: An outpatient 1-yr intervention program based on exercise, behavior, and nutrition therapy was performed.

Main Outcome Measures: Changes of weight status (sd score-body mass index), waist circumference, fetuin-A, blood pressure, lipids, transaminases, insulin resistance index homeostasis model assessment (HOMA), and prevalence of NAFLD (defined by liver ultrasound) were calculated.

Results: The 12 obese children with NAFLD had significantly higher fetuin-A levels (0.35 ± 0.07 g/liter) than the 24 obese children without NAFLD (0.29 ± 0.06 g/liter) and the 14 normal weight children (0.29 ± 0.05 g/liter). Fetuin-A levels were independent of age, pubertal stage, and gender. Fetuin-A correlated significantly to systolic (r = 0.50) and diastolic blood pressure (r = 0.41), insulin resistance index HOMA (r = 0.28), and high-density lipoprotein-cholesterol (r = −0.31). Changes of fetuin-A correlated significantly to changes of insulin resistance index HOMA (r = 0.34), systolic (r = 0.31) and diastolic blood pressure (r = 0.37), and waist circumferences (r = 0.36). Substantial weight loss in 21 children led to a significant decrease of fetuin-A and the prevalence of NAFLD in contrast to the 15 children without substantial weight loss.

Conclusions: Fetuin-A levels were higher in children with NAFLD, and were related to insulin resistance and to features of the MetS in both cross-sectional and longitudinal analyses. Therefore, fetuin-A might be a new promising link between obesity and its comorbidities.
Silica-supported Phosphomolybdic Acid-catalyzed Efficient Synthesis of 1,8-Dioxooctahydroxanthene and Tetrahydrochromene Derivatives
Authors: Das Biswanath , Krishnaiah Martha , Laxminarayana Keetha , Damodar Kongara , Kumar Duddukuri Nandan
Published: August 2008

Silica-supported phosphomolybdic acid was found to be an efficient heterogeneous catalyst for the synthesis of 1,8-dioxooctahydroxanthenes from aldehydes and dimedone and of tetrahydrochromenes from the same reaction mixture along with malononitrile. The products were formed in excellent yields. The catalyst can be recovered and reused.
Homocysteine enhances LDL fatty acid peroxidation, promoting microalbuminuria in type 2 diabetes
Authors: Kassab Asma , Ajmi Thouraya , Issaoui Manel , Chaeib Larbi , Miled Abdelhedi , Hammami Mohamed
Published: August 2008

Background

We aimed to establish the relationship between glycated haemoglobin (HbA1c), hypertension and microalbuminuria onset in type 2 diabetes. We also intended to ascertain the metabolic action of homocysteine on LDL fatty acids and on renal function.

Methods

The study was carried out on 200 patients with type 2 diabetes and 200 healthy subjects. HbA1c, apolipoprotein B (apo B) and microalbuminuria were measured using immunoturbidimetric methods. Cholesterol, peroxide, urea and uric acid were assayed using colorimetric methods. Creatinine clearance was calculated using the Cockroft-Gault equation. Homocysteine was measured by immunological fluorescence polarization. LDL fatty acids were quantified by gas chromatography.

Results

Creatinine and microalbuminuria significantly increased in type 2 diabetes when compared with controls. Microalbuminuria was significantly correlated with HbA1c and with the presence of high blood pressure. Homocysteinaemia significantly correlated with creatinine clearance in diabetes. Linoleic acid (C18:2ω6) did not differ between groups. C18:2ω6/C18:3ω3 ratio was three times higher in diabetics than in controls. Total saturated fatty acids, homocysteine, H2O2 and LDL-thiobarbituric reactive substances significantly increased in microalbuminuric when compared with normoalbuminuric diabetes. Total polyunsaturated fatty acids, arachidonic acid (C20:4ω6), LDL-cholesterol, apo B and creatinine clearance significantly decreased in microalbuminuric when compared with normoalbuminuric diabetes.

Conclusion

Microalbuminuria onset is associated with renal protein oxidation that is preceded by LDL fatty acid oxidation. The latter is initiated by H2O2 produced from an auto-oxidation of homocysteine and increased metabolism of arachidonic acid towards its pro-inflammatory eicosanoids. An oxidative stress state is the common ground of diffused vasculopathy.
An unusual cause of interference in a salicylate assay caused by mitochondrial acetoacetyl-CoA thiolase deficiency
Authors: Tilbrook L K , Slater J , Agarwal A , Cyriac J
Published: August 2008

Mitochondrial acetoacetyl-CoA thiolase deficiency (or beta-ketothiolase deficiency) is a rare metabolic disorder characterized by acute episodes of severe acidosis and ketosis. A case is presented of an 18-month-old boy who presented with vomiting and diarrhoea and was found to be markedly acidotic. When the acidosis persisted despite saline fluid boluses and bicarbonate correction, further investigations were undertaken. Routine biochemical investigation revealed detectable salicylate concentrations despite the parents denying its administration, which initially caused some diagnostic confusion. The results of urine organic acid analysis, however, confirmed that the diagnosis of mitochondrial acetoacetyl-CoA thiolase deficiency. The high concentrations of acetoacetate present in the patient's sample resulted in a false-positive reaction in the Trinder assay for salicylate.
Error models for immunoassays
Authors: Sadler William A
Published: August 2008

Background

For nearly 20 years, we and others have used a three-parameter power function as a direct estimation error model for immunoassays. The main application is imprecision profile plots (after translating from variance to coefficient of variation) but other uses include weighting functions for regression analysis and variance stabilizing transformations. Although generally successful, the intrinsic monotonicity of the function means that it fails to describe small but distinct increases in variance that occasionally occur near the assay detection limit.

Methods

A systematic comparison of five variance functions was undertaken, using randomly drawn samples from a large body of real immunoassay data.

Results

Variance function accuracy (hence imprecision profile accuracy) can be markedly improved, particularly near the assay detection limit, by employing a pair of complementary three-parameter power functions, together with a constrained four-parameter function, which provides for a variance turning point.

Conclusions

A set of rules, based on an objective goodness-of-fit statistic, can be used to automate presentation of the most appropriate function for any particular data-set. Flexibility is easily incorporated into the selection rules and is actually highly desirable to encourage ongoing evaluation with a wider variety of data. A Win32 computer program that performs the variance function estimation and plotting is freely available.
The relationship between estimated glomerular filtration rate and thyroid function: an observational study
Authors: Woodward Anne , McCann Steven , Al-Jubouri Mohammad
Published: August 2008

Background

Estimated glomerular filtration rate (eGFR) is now routinely reported by most National Health Service laboratories. There are many limitations when interpreting eGFR: thyroid dysfunction is not widely recognized as being one of these.

Methods

We extracted from the pathology computer system results of all patients with hypothyroidism and hyperthyroidism who also had serum creatinine measured. We also extracted creatinine data on euthyroid patients. eGFR was calculated using the simplified Modification of Diet in Renal Disease Study equation.

Results

The median eGFRs of the hypothyroid, euthyroid and hyperthyroid patients were 64, 77 and 107 mL/min/1.73 m2, respectively; all groups were significantly different from each other ( P < 0.001).

Conclusion

Thyroid dysfunction is associated with significant alterations in eGFR and actual GFR.
Platelet contamination causes large variation as well as overestimation of mitochondrial DNA content of peripheral blood mononuclear cells
Authors: Urata Michiyo , Koga-Wada Yui , Kayamori Yuzo , Kang Dongchon
Published: August 2008

Background

Alterations in the copy number of mitochondrial DNA (mtDNA) play a role in the pathogenesis of mitochondrial diseases and other many common diseases. Recently, the copy number of leukocyte mtDNA has been considered to serve as a biomarker to monitor or chase such diseases. Therefore, reproducible mtDNA measurement is required.

Methods

Peripheral blood mononuclear cells were prepared by a density-based method. The mtDNA/cell was measured by quantitative realtime polymerase chain reaction.

Results

The degree of platelet contamination varied to a large extent among preparations. The mtDNA copy numbers per mononuclear cell were 269 ± 51 and 146 ± 14 in the samples before and after the platelet depletion, respectively.

Conclusion

A density-based mononuclear cell preparation causes heavy platelet contamination. The platelet depletion from a sample is particularly important for comparing the mtDNA contents between different dates or between different patients.
Use of routine clinical laboratory data to define reference intervals
Authors: Shine Brian
Published: August 2008

Background

Reference intervals are used to distinguish between healthy and diseased state. Ideally, they are defined using specimens only from ‘healthy’ individuals, but this is often difficult or impossible. In order to use routine clinical laboratory data, outliers must be removed before the underlying distribution and changes related to age and sex can be modelled. This paper illustrates the process for plasma alkaline phosphatase (ALP). ALP levels are high in infancy and childhood, peak in adolescence, are stable from the early 20s and rise after the fourth decade. Three types of normalizing transformations (Logarithmic, Box-Cox and Cole's LMS) are compared.

Methods

Single ALP results from 75,328 individuals aged 0–80 years were binned by sex and age. The normalizing transformations were applied to each bin, outliers were removed and the normalizing transformations were reapplied to the remaining data. The normality of the transformed data was assessed by normal score plots and the Kolmogorov-Smirnov test. Fractional polynomials were used to model the underlying parameters of the transformations and the derived parametric reference intervals (mean ± 1.96 standard deviations), separately for each sex as a whole and partitioned into two or three age ranges, with overlapping to give smooth transitions.

Results

All transformations yielded acceptably normal data, but the LMS method gave the closest approximation to normal. Outlier rates were similar for each method. The derived reference ranges were similar for all the three methods. Splitting the data-set into several segments resulted in a better fit with the peak seen in adolescence.

Conclusion

Routine clinical laboratory specimens can be used to derive reference intervals.
Selenium status in patients with aspirin-induced asthma
Authors: Hassan Afaf M
Published: August 2008

Background

Platelets are involved in the pathogenesis of aspirin-induced asthma (AIA). AIA patients suffer from an active disease despite avoidance of aspirin, and it has been suggested that administration of aspirin to these patients increases the generation of immediate oxygen products of arachidonic acid, 12-hydroperoxyeicosatetraenoic acid (12-HPETE), in their platelets. 12-HPETE further activates the 5-lipoxygenase of leukotriene B4-producing inflammatory macrophages precipitating an acute asthmatic attack. Glutathione peroxidase (GPX) has the antioxidant capacity to reduce 12-HPETE, and thus modulate the arachidonic acid metabolic cascade. There is evidence that selenium (Se) nutrition can influence asthma but Se status in AIA patients has not received much attention.

Methods

We measured Se concentrations and GPX activities in platelets and plasma from 13 patients with AIA. Age- and sex-matched healthy individuals served as the control group.

Results

Patients with AIA had significantly higher median platelet Se concentration (102 ng/mg platelet protein) when compared with controls (49 ng/mg platelet protein, P = 0.003). Plasma Se concentrations in patients with AIA and controls were not significantly different ( P = 0.59). Median platelet GPX activity was significantly higher in patients with AIA (102.7 mU/mg platelet protein) than in controls (66 mU/mg protein) ( P = 0.05). The patient and control groups when combined showed weak, but significant correlation between platelet Se concentration and platelet GPX activity ( r = 0.44; P = 0.03).

Conclusion

It is proposed that the higher platelet Se concentration observed in AIA patients contributed to the higher platelet GPX activity seen in these patients. Such an enhanced antioxidant defence system might represent an adaptive response to protect against increasing free radical production by inflammatory cells in AIA and help decelerate ongoing respiratory hypersensitivity.
Audit of acute hypoglycaemia in children: re-audit of procedures for diagnosis
Authors: Lang Timothy F , Cardy David , Carson Dennis , Loughrey Clodagh M , Hanna Elinor
Published: August 2008

Background

A protocol exists for the collection of samples to investigate unexplained hypoglycaemia, termed the ‘hypopack’. These packs are kept in Accident and Emergency departments and neonatal special care baby units throughout Northern Ireland and most wards of the Regional Children's Hospital. A retrospective audit of 107 hypopacks received between July 2001 and December 2003 highlighted a number of problems: samples collected when the patient was receiving dextrose, incomplete clinical history provided, insufficient and haemolysed samples received and poor filing of reports in charts. These were addressed by re-designing the request form, updating the protocol and introducing a summative report. The new protocol was introduced in April 2006.

Methods

The aim of this study is to assess whether the revised protocol improved utility of the hypopack. A retrospective re-audit of 100 hypopacks received between April 2006 and May 2007 was performed.

Results

Forty-nine percent of patients were hypoglycaemic (<2.6 mmol/L) compared with 35% in the original audit. In both audits, 33% of laboratory reports were missing from patients' charts. One case of medium-chain acyl-CoA dehydrogenase deficiency, three cases of hyperinsulinism and two endocrine-related cases were identified.

Conclusions

The new hypopack protocol has increased the number of appropriately performed investigations. Provision of information concerning dextrose infusion has assisted the interpretation of the hypopack results.
Neonatal jaundice: a critical review of the role and practice of bilirubin analysis
Authors: Kirk Jean M
Published: August 2008

Neonatal jaundice is common, and usually harmless, because of physiological jaundice or breast-feeding. In some neonates unconjugated bilirubin concentration, coupled with other risk factors, is sufficient to allow free bilirubin to cross the blood-brain barrier and cause kernicterus. Another subgroup of infants is jaundiced because of elevated conjugated bilirubin; a marker for a number of pathological conditions. Bilirubin measurement must identify those infants at risk. Transcutaneous bilirubin measurement is increasingly used in healthy infants, especially before early discharge or at home, to assess the need for laboratory bilirubin measurement. Transcutaneous measurements are not covered by laboratory quality assessment schemes. Guidelines on management of neonatal jaundice utilize age in hours and other risk factors to define bilirubin action thresholds, which may be as low as 100 μmol/L for sick premature infants, whereas early discharged babies may only present after bilirubin concentrations are extremely high. Hence, there is a requirement for accurate total bilirubin measurement from <100 to >500 μmol/L, with sufficient precision to assess the rate of bilirubin change with time. Babies presenting with late jaundice always require conjugated bilirubin measurement. It is of concern that many total and direct bilirubin automated kit methods suffer from haemolysis interference, while use of in-house methods or modification of commercial methods has virtually disappeared. External quality assessment has a vital role in providing data on different methods' performance, including accuracy, precision and susceptibility to interference. Laboratories should consider whether their adult bilirubin methods are suitable for neonates.