bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of cognitive therapy on the longitudinal development of
psychotic experiences in people at high risk of developing
psychosis
Authors: French P. , Shryane N. , Bentall R. P. , Lewis S. W. , Morrison A. P.
Published: November 2007

Background

There have been recent advances in the identification of people at high
risk of psychosis and psychological treatments have shown promise for
prevention

Aims

To compare the longitudinal course of psychotic experiences and emotional
dysfunction in high-risk participants receiving cognitive therapy with
those receiving treatment as usual

Method

Data from a recent randomised controlled trial of cognitive therapy for
people at risk of developing psychosis were utilised to examine three
different statistical models that were based on 432 measurements of
psychotic experiences and 421 of emotional dysfunction
(anxiety–depression) contributed by 57 participants across the 13
measurement occasions (monthly monitoring for a year)

Results

Psychotic experiences and emotional dysfunction were correlated and
decreased significantly over the course of the study, with most
improvement in the early months. The reduction in positive symptoms, but
not emotional dysfunction, was enhanced by allocation to cognitive
therapy

Conclusions

Psychotic experiences and emotional dysfunction appear to interact in
people at risk of developing psychosis. There appears to be a specific
benefit of cognitive therapy
Aripiprazole in the treatment of the psychosis
prodrome
Authors: Woods Scott W. , Tully Elizabeth M. , Walsh Barbara C. , Hawkins Keith A. , Callahan Jennifer L. , Cohen Shuki J. , Mathalon Daniel H. , Miller Tandy J. , McGlashan Thomas H.
Published: November 2007

Background

Research studies for the treatment of the putative prodromal phase of
psychotic disorders have begun to appear

Aims

To obtain preliminary evidence of the short-term efficacy and safety of
aripiprazole treatment in people with the psychosis prodrome

Method

Fifteen participants meeting prodrome criteria (mean age 17.1 years,
s.d.=5.5) enrolled in an open-label, single-site trial with
fixed-flexible dosing of aripiprazole (5–30 mg/day) for 8 weeks

Results

In the mixed-effects repeated-measures analysis, improvement from
baseline on the Scale of Prodromal Symptoms total score was statistically
significant by the first week. No participant converted to psychosis and
13 completed treatment. Neuropsychological measures showed no consistent
improvement; mean weight gain was 1.2 kg. Akathisia emerged in 8
participants, but the mean Barnes Akathisia Scale score fell to baseline
levels by the final visit. Adverse events were otherwise minimal

Conclusions

Aripiprazole shows a promising efficacy and safety profile for the
psychosis prodrome. Placebo-controlled studies are indicated
Provision of child and adolescent mental health in-patient services in England between 1999 and 2006
Authors: O'Herlihy Anne , Lelliott Paul , Bannister Debbie , Cotgrove Andrew , Farr Hannah , Tulloch Simon
Published: November 2007

AIMS AND METHOD

In 1999, child and adolescent mental health (CAMH) in-patient provision was unevenly distributed across England. A repeat of a1999 bed count survey was conducted in 2006 to determine whether change had occurred in response to government policy.

RESULTS

Total bed numbers in England were found to have increased by 284; 69% of the increase is due to the independent sector, whose market share has risen from 25% in 1999 to 36% in 2006. Regions with the highest number of beds in 1999 have increased bed numbers more than areas with the lowest number of beds in1999 (8.3 v. 3.6 beds per million population). In units that admit only children under the age of 14, there has been a 30% reduction in beds available (123 to 86).

CLINICAL IMPLICATIONS

Inequity in provision of CAMH inpatient services has increased despite government policy to the contrary. We speculate that this might be partly due to fragmented and local commissioning, and the effects of market forces operating as a result of increasing privatisation.
Combination of Trastuzumab and Tanespimycin (17-AAG, KOS-953) Is Safe and Active in Trastuzumab-Refractory HER-2–Overexpressing Breast Cancer: A Phase I Dose-Escalation Study
Authors: Modi Shanu , Stopeck Alison T. , Gordon Michael S. , Mendelson David , Solit David B. , Bagatell Rochelle , Ma Weining , Wheler Jennifer , Rosen Neal , Norton Larry , Cropp Gillian F. , Johnson Robert G. , Hannah Alison L. , Hudis Clifford A.
Published: November 2007

Purpose

This phase I study examined whether a heat shock protein (Hsp) 90 inhibitor tanespimycin (17-AAG; KOS-953) could be administered safely in combination with trastuzumab at a dose that inhibits Hsp90 function in vivo in lymphocytes.

Patients and Methods

Patients with an advanced solid tumor progressing during standard therapy were eligible. Patients were treated with weekly trastuzumab followed by intravenous tanespimycin, assessed in escalating dose levels.

Results

Twenty-five patients were enrolled onto four tanespimycin dose levels: 225 (n = 4), 300 (n = 3), 375 (n = 8), and 450 mg/m2 (n = 10). Dose-limiting toxicity (DLT) was observed at the third and fourth cohort (1 patient each): more than 2-week delay for grade 4 fatigue/grade 2 nausea and anorexia (375 mg/m2); more than 2-week delay for thrombocytopenia (450 mg/m2). Drug-related grade 3 toxicity included emesis, increased ALT, hypersensitivity reactions (two patients each), and drug-induced thrombocytopenia (n = 1). Common mild to moderate toxicities included fatigue, nausea, diarrhea, emesis, headache, rash/pruritus, increased AST/ALT, and anorexia. Pharmacokinetic analysis demonstrated no difference in tanespimycin kinetics with or without trastuzumab. Pharmacodynamic testing showed reactive induction of Hsp70 (a marker of Hsp90 inhibition) in lymphocytes at all dose levels. Antitumor activity was noted (partial response, n = 1; minor response, n = 4; stable disease ≥ 4 months, n = 4). Tumor regressions were seen only in patients with human epidermal growth factor receptor 2 (HER-2)-positive metastatic breast cancer.

Conclusion

Tanespimycin plus trastuzumab is well tolerated and has antitumor activity in patients with HER-2+ breast cancer whose tumors have progressed during treatment with trastuzumab. These data suggest that Hsp90 function can be inhibited in vivo to a degree sufficient to cause inhibition of tumor growth.
Physiological Concentration of 17β-Estradiol on Sympathetic Reinnervation in Ovariectomized Infarcted Rats
Authors: Lee Tsung-Ming , Lin Mei-Shu , Chang Nen-Chung
Published: November 2007

17β-Estradiol (E2) has been shown to exert antiarrhythmic effect after myocardial infarction; however, the mechanisms remain unclear. This study was performed to determine whether E2 exerts beneficial effects through attenuated sympathetic hyperreinnervation after infarction. Two weeks after ovariectomy, female Wistar rats were assigned to coronary artery ligation or sham operation. Twenty-four hours after coronary ligation, rats underwent one of five treatments: 1) sc vehicle treatment (control), 2) sc E2 treatment, 3) sc E2 treatment + tamoxifen (a potent estrogen receptor antagonist), 4) bosentan (an endothelin receptor blocker), or 5) sc E2 treatment + bosentan and followed for 4 wk. Myocardial endothelin-1 and norepinephrine levels at the remote zone revealed a significant elevation in control infarcted rats, compared with sham-operated rats, which is consistent with sympathetic hyperinnervation after infarction. Sympathetic hyperinnervation was blunted after giving the rats either E2 or bosentan, assessed by immunohistochemical analysis of tyrosine hydroxylase, growth-associated protein 43 and neurofilament, and Western blotting and real-time quantitative RT-PCR of nerve growth factor. Arrhythmic scores during programmed stimulation in E2-treated infarcted rats were significantly lower than in control-infarcted rats. Addition of bosentan did not have additional beneficial effects, compared with rats treated with E2 alone. The beneficial effect of E2 on sympathetic hyperinnervation was abolished by tamoxifen. Our data indicated that E2 has a role for sympathetic hyperinnervation after infarction, probably through an endothelin-1-depedent pathway. Chronic administration of E2 after infarction may attenuate the arrhythmogenic response to programmed electrical stimulation.
Physiological, morphological and behavioural effects of selecting zebra finches for divergent levels of corticosterone
Authors: Roberts M. L. , Buchanan K. L. , Hasselquist D. , Bennett A. T. D. , Evans M. R.
Published: November 2007

The effects of environmental stress on the physiology and behaviour of higher vertebrates has become an important avenue of research in recent years. Evidence from recent studies has suggested that the avian stress-related hormone corticosterone (CORT) may play a role in immunocompetence and sexual selection. We tested whether CORT is immunosuppressive by studying humoral and cell-mediated immune responses in populations of captive zebra finches selected for divergent peak levels of CORT. We also investigated whether selection for peak CORT has an effect on the quality of several sexually selected regions of the male zebra finch; in addition we compared morphometric parameters and the dominance ranking in males from the different selection lines. We also tested whether different components of the immune system compete for limited resources. We found that selection for divergent levels of peak CORT had little effect on humoral immunity, male sexual signal quality or dominance ranking. However, contrary to expectations, we did find a positive relationship between CORT titre and cell-mediated immunity, as well as a greater cell-mediated response in the birds selected for high CORT titre than those selected for low CORT titre. Consistent with predictions, significant negative relationships were found between both testosterone and CORT titre on humoral immunity. Birds from the low CORT lines were significantly larger in terms of skeletal size than those from the high CORT lines. Overall, our results suggest that the cell-mediated immune response is associated with a reduction in the humoral response, but only in males, and that there is no simple relationship between peak CORT levels and immune function.
Mechanical and energetic factors underlying gait transitions in bluegill sunfish (Lepomis macrochirus)
Authors: Kendall Jennifer L. , Lucey Kaitlyn S. , Jones Emily A. , Wang Jasmine , Ellerby David J.
Published: November 2007

As their swimming speed increased, bluegill sunfish (Lepomis macrochirus) switched from pectoral-fin-powered labriform swimming to undulations of the body axis. This gait transition occurred at a mean swimming speed of 0.24±0.01 m s–1 and a pectoral fin beat frequency of 2.79±0.11 Hz (mean ± s.e.m., N=6). The power output available from the main upstroke (adductor profundus) and downstroke (abductor superficialis) muscles, measured using the work-loop technique was maximal at the gait transition point. The cost of transport,measured by respirometry, increased as the fish switched from labriform to undulatory swimming. Our data show that bluegill changed gait as swimming speed increased to recruit additional muscle mass, rather than to maximize economy, as is the case for many terrestrial animals.
Holdfast heroics: comparing the molecular and mechanical properties ofMytilus californianusbyssal threads
Authors: Harrington Matthew J. , Waite J. Herbert
Published: November 2007

The marine mussel Mytilus californianus Conrad inhabits the most wave-exposed regions of the rocky intertidal by dint of its extraordinary tenacity. Tenacity is mediated in large part by the byssus, a fibrous holdfast structure. M. californianus byssal threads, which are mechanically superior to the byssal threads of other mytilids, are composed almost entirely of a consortium of three modular proteins known as the preCols. In this study,the complete primary sequence of preCols from M. californianus was deduced and compared to that of two related species with mechanically inferior byssal threads, M. edulis Linnaeus and M. galloprovincialisLamarck in order to explore structure–function relationships.

The preCols from M. californianus are more divergent from the other two species than they are from one another. However, the degree of divergence is not uniform among the various domains of the preCols, allowing us to speculate on their mechanical role. For instance, the extra spider silk-like runs of alanine-rich sequence in the flanking domains of M. californianus may increase crystalline order, enhancing strength and stiffness. Histidine-rich domains at the termini, in contrast, are highly conserved between species, suggesting a mechanical role common to all three. Mechanical testing of pH-treated and chemically derivatized distal threads strongly suggests that histidine side chains are ligands in reversible,metal-mediated cross-links in situ. By combining the mechanical and sequence data, yield and self-healing in the distal region of threads have been modeled to emphasize the intricate interplay of enthalpic and entropic effects during tensile load and recovery.
Metabolic inactivation of the circadian transmitter, pigment dispersing factor (PDF), by neprilysin-like peptidases in Drosophila
Authors: Isaac R. Elwyn , Johnson Erik C. , Audsley Neil , Shirras Alan D.
Published: November 2007

Recent studies have firmly established pigment dispersing factor (PDF), a C-terminally amidated octodecapeptide, as a key neurotransmitter regulating rhythmic circadian locomotory behaviours in adult Drosophila melanogaster. The mechanisms by which PDF functions as a circadian peptide transmitter are not fully understood, however; in particular, nothing is known about the role of extracellular peptidases in terminating PDF signalling at synapses. In this study we show that PDF is susceptible to hydrolysis by neprilysin, an endopeptidase that is enriched in synaptic membranes of mammals and insects. Neprilysin cleaves PDF at the internal Ser7–Leu8 peptide bond to generate PDF1-7 and PDF8-18. Neither of these fragments were able to increase intracellular cAMP levels in HEK293 cells cotransfected with the Drosophila PDF receptor cDNA and a firefly luciferase reporter gene, confirming that such cleavage results in PDF inactivation. The Ser7–Leu8 peptide bond was also the principal cleavage site when PDF was incubated with membranes prepared from heads of adult Drosophila. This endopeptidase activity was inhibited by the neprilysin inhibitors phosphoramidon (IC50, 0.15 μmol l–1) and thiorphan (IC50, 1.2 μmol l–1). We propose that cleavage by a member of the Drosophila neprilysin family of endopeptidases is the most likely mechanism for inactivating synaptic PDF and that neprilysin might have an important role in regulating PDF signals within circadian neural circuits.
Calculation of temperatures in a sliding wheel/rail system and implications for wheel steel development
Authors: Sawley K J
Published: November 2007

Railway wheel failure occurs when metal spalls from the tread to produce flat or out-of-round wheels that cause high dynamic forces. Spalls initiate in brittle martensite formed by the frictional heat produced during wheel slide. The current paper calculates the temperatures developed in the sliding wheel and discusses consequences of the rates of change of temperature on metallurgical means of avoiding spalls.
An experimental study of the influence of parapets on the aerodynamic loads under cross wind on a two-dimensional model of a railway vehicle on a bridge
Authors: Barcala M A , Meseguer J
Published: November 2007

Aerodynamic loads on railway vehicles under cross winds are governed both by the shapes of the vehicles and of the surroundings. Apart from the inertial loads due to accelerations acting on the vehicle, aerodynamic loads due to cross winds are of paramount importance in the lateral equilibrium of the vehicle, in such a way that if the lateral wind speed becomes larger than a threshold value, overturning of the vehicle can take place. The degree of danger of overturning increases when the train is on a bridge, the reason being that the velocity in the atmospheric boundary layer grows as the height increases, leaving aside the fact that at ground level there may be other elements acting as windbreaks (mainly vegetation). The effects of different types of solid parapets on the side force and rolling moment acting on a 1/70 scale two-dimensional model of a typical high-speed train vehicle have been measured by wind-tunnel tests, both when the vehicle is placed on a bridge and when it is on ground. Experimental results show that, as one could expect, aerodynamic loads decrease as the height of the windbreak increases, and that solid parapets seem to be more effective on bridges than on ground.
Rapid Prototyping Improves Research on Red-Light-Running Behavior
Authors: Perez Miguel A. , Doerzaph Zachary R. , Lee Suzanne E. , Neale Vicki L.
Published: November 2007

FEATURE AT A GLANCE: Unintentional red-light running is a relatively rare occurrence in everyday driving, but it can lead to serious crashes. While developing systems that warn drivers who are about to run a red light, we conducted tests that allowed us to place naive drivers in unexpected red-light-running scenarios on a test track. By adapting rapid prototyping design concepts, we were able to quickly iterate through research scenarios and develop a method that was repeatable, efficient, and realistic. We discuss lessons learned and pitfalls to avoid in the application of rapid prototyping concepts to human factors research design.
Infant Botulism: A 30-Year Experience Spanning the Introduction of Botulism Immune Globulin Intravenous in the Intensive Care Unit at Childrens Hospital Los Angeles
Authors: Underwood Karen , Rubin Sarah , Deakers Timothy , Newth Christopher
Published: November 2007

OBJECTIVE. To report a tertiary care hospital's 30-year experience with the diagnosis, treatment, and outcome of infant botulism in the PICU before and after the availability of Botulism Immune Globulin Intravenous.

METHODS. This was a retrospective medical chart review of the 67 patients who had received a diagnosis of infant botulism and were admitted to the ICU from 1976 to 2005. The ages on presentation, length of hospital stay, length of ICU stay, length of mechanical ventilation, and type of botulism toxin were recorded and compared for patients who had received Botulism Immune Globulin Intravenous and those who had not. On the basis of our results, conclusions were drawn regarding the effect of Botulism Immune Globulin Intravenous on the morbidity of infant botulism.

RESULTS. Sixty-seven patients’ charts were reviewed; 23 male and 29 female patients did not receive Botulism Immune Globulin Intravenous. Of patients who did not receive Botulism Immune Globulin Intravenous, the median age at presentation was 71 days, median length of hospital stay was 35 days, ICU stay was 24 days, and duration of mechanical ventilation was 17 days. A total of 40% had type A toxin, and 60% had type B toxin. There was a significant difference between patients with toxin types A and B in length of hospital stay but not length of ICU stay or mechanical ventilation. Patients with type A toxin were significantly older than patients with type B toxin. Fifteen children received Botulism Immune Globulin Intravenous. There were statistically significant differences in length of hospital stay, length of ICU stay, and length of mechanical ventilation between patients who received Botulism Immune Globulin Intravenous and those who did not.

CONCLUSIONS. The use of Botulism Immune Globulin Intravenous significantly decreased the length of ICU stay, length of mechanical ventilation, and overall hospital stay in children with infant botulism.
State of the Evidence on Acute Asthma Management in Children: A Critical Appraisal of Systematic Reviews
Authors: Boluyt Nicole , van der Lee Johanna H. , Moyer Virginia A. , Brand Paul L. P. , Offringa Martin
Published: November 2007

OBJECTIVE. Our goal was to evaluate clinical, methodologic, and reporting aspects of systematic reviews on the management of acute asthma in children.

METHODS. We undertook a systematic review of systematic reviews on acute asthma management in children. We identified eligible reviews by searching the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, Medline, and Embase 1990 to March 2006. Data were extracted on clinical issues, methodologic characteristics, and results of the reviews. Methodologic quality was assessed with the Overview Quality Assessment Questionnaire and with additional questions on heterogeneity. Separate reporting on children in mixed adult-pediatric population reviews was assessed. Methodologic quality of systematic reviews published in peer-reviewed journals was compared with Cochrane reviews.

RESULTS. A total of 23 systematic reviews were included: 14 were published in the Cochrane Library, and 9 were published in peer-reviewed journals. Eight reviews included children only, and 15 were mixed-population reviews. The majority of reviews defined the study population as having “acute asthma” without a more precise definition, and 16 different health outcomes were reported. The overall quality according to the Overview Quality Assessment Questionnaire was good, with Cochrane reviews showing minimal flaws and journal reviews showing minor flaws (median scores: 7 vs 5). Results on children were reported separately in 8 of 15 mixed-population reviews. Clinical heterogeneity was explored in only 2 of 23 reviews, and the methods used to identify and address heterogeneity were diverse.

CONCLUSIONS. The methodologic quality of both the Cochrane and journal reviews on the management of acute asthma in children seems good, with Cochrane reviews being more rigorous. However, their usefulness for clinical practice is hampered by a lack of clear definitions of included populations, clinically important health outcomes, and separate reporting on children in mixed reviews. A major threat to these reviews’ validity is the insufficient identification and handling of heterogeneity.
Preventive Care for Children in Low-Income Families: How Well Do Medicaid and State Children's Health Insurance Programs Do?
Authors: Perry Cynthia D. , Kenney Genevieve M.
Published: November 2007

OBJECTIVE. Child health problems that are caused or exacerbated by health behaviors remain a leading cause of medical spending for children. We examined receipt of clinician advice by low-income children, comparing children who had public insurance with those who had private insurance, as well as with children who were uninsured for part or all of the year.

METHODS. We used children who were aged 3 to 17 and living in families with incomes of <250% of the federal poverty level in the Medical Expenditure Panel Survey data from 2001 to 2003 to estimate linear probability models on receipt of preventive advice. The main outcome measures were receipt of clinician's advice about healthy eating, physical activity, the harmful effects of smoking in the home, proper safety restraints in a car, and use of a bicycle helmet. We also examined 2 related barriers to receiving clinician advice: whether the child had any preventive care visits in the past year and whether the child had a usual source of care other than a hospital emergency department.

RESULTS. Publicly insured children were more likely than privately insured, full-year–uninsured children, and part-year–uninsured children to have had a preventive care visit in the past year, but regardless of health insurance group, many children went without preventive care. Even conditional on having had a preventive care visit, 48% did not receive clinician advice in any of the areas measured, and 41% of the overweight children were advised about neither healthy eating nor exercise in the past year.

CONCLUSIONS. Enrolling more uninsured children in Medicaid and State Children's Health Insurance Programs could improve the chances that families receive advice about health behaviors and injury prevention; however, nearly half of the children who were insured for the entire year did not receive important advice from their clinicians.
Pediatric Preparedness of US Emergency Departments: A 2003 Survey
Authors: Gausche-Hill Marianne , Schmitz Charles , Lewis Roger J.
Published: November 2007

OBJECTIVES. Our goal was to assess the degree of pediatric preparedness of emergency departments in the United States.

METHODS. A closed-response survey based on the American Academy of Pediatrics/American College of Emergency Physicians joint policy statement, “Care of Children in the Emergency Department: Guidelines for Preparedness,” was mailed to 5144 emergency department medical and nursing directors. A weighted preparedness score (scale of 0–100) was calculated for each emergency department.

RESULTS. A total of 1489 useable surveys (29%) were received, with 62% completed by emergency department medical directors. Eighty-nine percent of pediatric (age: 0–14 years) emergency department visits occur in non–children's hospitals, 26% of visits occur in rural or remote facilities, and 75% of responding emergency departments see <7000 children per year. The vast majority of visits (89%) occur in emergency department areas shared with adult patients; 6% occur in a separate pediatric emergency department. Only 6% of emergency departments had all recommended equipment and supplies. Emergency departments frequently lacked laryngeal mask airways for children (50%) and neonatal or infant equipment. In contrast, recommended medications were more uniformly available, as were transfer policies for medical or surgical intensive care. Fifty-two percent of emergency departments reported having a quality improvement/performance improvement plan for pediatric emergency patients, and 59% of respondents were aware of the American Academy of Pediatrics/American College of Emergency Physicians guidelines. The median pediatric-preparedness score for all emergency departments was 55. Pediatric-preparedness scores were higher for facilities with higher pediatric volume, facilities with physician and nursing coordinators for pediatrics, and facilities with respondents who reported awareness of the guidelines.

CONCLUSION. Pediatric preparedness of hospital emergency departments demonstrates opportunities for improvement.
Predicting Language at 2 Years of Age: A Prospective Community Study
Authors: Reilly Sheena , Wake Melissa , Bavin Edith L. , Prior Margot , Williams Joanne , Bretherton Lesley , Eadie Patricia , Barrett Yin , Ukoumunne Obioha C.
Published: November 2007

OBJECTIVE. This article responds to evidence gaps regarding language impairment identified by the US Preventive Services Task Force in 2006. We examine the contributions of putative child, family, and environmental risk factors to language outcomes at 24 months of age.

METHODS. A community-ascertained sample of 1720 infants who were recruited at 8 months of age were followed at ages 12 and 24 months in a prospective, longitudinal study in metropolitan Melbourne, Australia. Outcomes at 24 months were parent-reported infant communication (Communication and Symbolic Behavior Scales and MacArthur-Bates Communicative Development Inventories vocabulary production score). Putative risk factors were gender, preterm birth, birth weight, multiple birth, birth order, socioeconomic status, maternal mental health, maternal vocabulary and education, maternal age at birth of child, non–English-speaking background, and family history of speech-language difficulties. Linear regression models were fitted to total standardized Communication and Symbolic Behavior Scales and Communicative Development Inventories vocabulary production scores; a logistic regression model was fitted to late-talking status at 24 months.

RESULTS. The regression models accounted for 4.3% and 7.0% of the variation in the 24-month Communication and Symbolic Behavior Scales and Communicative Development Inventories scores, respectively. Male gender and family history were strongly associated with poorer outcomes on both instruments. Lower Communication and Symbolic Behavior Scales scores were also associated with lower maternal vocabulary and older maternal age. Lower vocabulary production scores were associated with birth order and non–English-speaking background. When the 12-month Communication and Symbolic Behavior Scales Total score was added as a covariate in the linear regression of 24-month Communication and Symbolic Behavior Scales Total score, it was by far the strongest predictor.

CONCLUSIONS. These early risk factors explained no more than 7% of the variation in language at 24 months. They seem unlikely to be helpful in screening for early language delay.
Expression of the Epithelial Sodium Channel in Airway Epithelium of Newborn Infants Depends on Gestational Age
Authors: Helve Otto , Janér Cecilia , Pitkänen Olli , Andersson Sture
Published: November 2007

OBJECTIVE. In the newborn infant, removal of fetal lung liquid from the airways depends on ion transport through the airway epithelium. The epithelial sodium channel is considered rate limiting for the postnatal clearance of lung liquid, but it is unknown whether during the early postnatal period the expression of epithelial sodium channel is associated with maturity. Our objective was to study the relationship between gestational age and epithelial sodium channel expression in airway epithelium.

METHODS. In 90 newborn infants (preterm [gestational age < 37]: n = 29; term [gestational age ≥ 37]: n = 61), we measured the expression of epithelial sodium channel (reported as attomoles of subunit expression normalized to femtomoles of expression of cytokeratin 18) in nasal epithelium at 1 to 5 and 22 to 28 hours after birth.

RESULTS. At 1 to 5 hours postnatally, airway expression of α-, β-, and γ-subunits of epithelial sodium channel was lower in preterm than in term infants. At this time point, significant correlations existed between gestational age and airway expression of α- and β-epithelial sodium channel. By 22 to 28 hours after birth, only the expression of β-epithelial sodium channel had decreased significantly in the preterm infants, whereas the expression of all epithelial sodium channel subunits had decreased significantly in the term infants. At this time point, no difference in expression of any of the subunits was found between preterm and term infants.

CONCLUSIONS. Airway expression of epithelial sodium channel at 1 to 5 hours of age is significantly lower in preterm than in term infants. Low postnatal expression of α-, β-, and γ-epithelial sodium channel subunits in the airway epithelium may contribute to the development of respiratory distress in the preterm infant.
Mitochondrial Disease: A Practical Approach for Primary Care Physicians
Authors: Haas Richard H. , Parikh Sumit , Falk Marni J. , Saneto Russell P. , Wolf Nicole I. , Darin Niklas , Cohen Bruce H.
Published: November 2007

Notorious variability in the presentation of mitochondrial disease in the infant and young child complicates its clinical diagnosis. Mitochondrial disease is not a single entity but, rather, a heterogeneous group of disorders characterized by impaired energy production due to genetically based oxidative phosphorylation dysfunction. Together, these disorders constitute the most common neurometabolic disease of childhood with an estimated minimal risk of developing mitochondrial disease of 1 in 5000. Diagnostic difficulty results from not only the variable and often nonspecific presentation of these disorders but also from the absence of a reliable biomarker specific for the screening or diagnosis of mitochondrial disease. A simplified and standardized approach to facilitate the clinical recognition of mitochondrial disease by primary physicians is needed. With this article we aimed to improve the clinical recognition of mitochondrial disease by primary care providers and empower the generalist to initiate appropriate baseline diagnostic testing before determining the need for specialist referral. This is particularly important in light of the international shortage of metabolism specialists to comprehensively evaluate this large and complex disease population. It is hoped that greater familiarity among primary care physicians with the protean manifestations of mitochondrial disease will facilitate the proper diagnosis and management of this growing cohort of pediatric patients who present across all specialties.
Cardiac Safety of Central Nervous System Stimulants in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder
Authors: Winterstein Almut G. , Gerhard Tobias , Shuster Jonathan , Johnson Michael , Zito Julie M. , Saidi Arwa
Published: November 2007

OBJECTIVES. Case reports have raised concerns about the risk of cardiac events associated with central nervous system stimulants for the treatment of attention-deficit/hyperactivity disorder.

PATIENTS AND METHODS. This was a retrospective cohort study that used 10 years (July 1994 to June 2004) of Florida Medicaid claims data cross-linked to Vital Statistics Death Registry data. The cohort was composed of all youth 3 to 20 years old who were newly diagnosed with attention-deficit/hyperactivity disorder. Each month of follow-up was classified according to stimulant claims (methylphenidate, amphetamines, and pemoline) as current use (active stimulant claim), former use (time after periods of current use), or nonuse (time preceding the first stimulant claim, including follow-up of youth who were never exposed to stimulants). The study's end points were (1) cardiac death, (2) first hospital admission for cardiac causes or (3) first emergency department visit for cardiac causes. Risks were compared with time-dependent Cox regression analysis adjusting for various cardiac risk factors.

RESULTS. During 124932 person-years of observation (n = 55383), 73 youth died, 5 because of cardiac causes. No cardiac death occurred during 42612 person-years of stimulant use. Hospital admissions for cardiac cause occurred for 27 children (8 during stimulant use, 11 during 35671 person-years of former use, and 8 during 46649 person-years of nonuse); and 1091 children visited the emergency department for cardiac causes (8.7 per 1000 person-years). Current stimulant use was associated with a 20% increase in the hazard for emergency department visits when compared with nonuse. No increased risk was found for periods of former use when compared with nonuse.

CONCLUSIONS. Incidence rates of cardiac events requiring hospitalization were small and similar to national background rates. Stimulants were associated with an increase in cardiac emergency department visits. More evidence is needed that addresses the long-term risk/benefit of the various treatment options and the effect of other cardiac risk factors and comedications.
Gender Differences in Presentation and Course of Disease in Pediatric Patients With Crohn Disease
Authors: Gupta Neera , Bostrom Alan G. , Kirschner Barbara S. , Ferry George D. , Winter Harland S. , Baldassano Robert N. , Gold Benjamin D. , Abramson Oren , Smith Terry , Cohen Stanley A. , Heyman Melvin B.
Published: November 2007

OBJECTIVE. The objective of this study was to determine gender differences in pediatric patients with Crohn disease.

METHODS. We conducted a retrospective cohort study of 989 consecutive pediatric patients (566 boys, 423 girls) who had Crohn disease (aged 0 to 17 years at diagnosis) by using the Pediatric IBD Consortium Registry. Uniform data were analyzed to compare the presentation and course of disease according to gender.

RESULTS. Median follow-up time was 2.8 years. Mean ± SD age at diagnosis of inflammatory bowel disease (11.5 ± 3.8 years) did not differ by gender. Compared with boys, girls had a higher prevalence of mouth sores at symptom onset and a higher prevalence of hypoalbuminemia at the time of diagnosis. Location of disease did not differ by gender. A higher proportion of girls had abnormal anti–outer membrane porin of Escherichia coli levels compared with boys. Girls were at increased risk for erythema nodosum/pyoderma gangrenosum and decreased risk for growth failure compared with boys.

CONCLUSIONS. Girls appear to have an overall more severe course of disease; however, boys are at increased risk for developing growth failure. Disease course and the impact of disease severity on growth according to gender in pediatric Crohn disease require prospective study.
Pediatric Myocarditis: Emergency Department Clinical Findings and Diagnostic Evaluation
Authors: Freedman Stephen B. , Haladyn J. Kimberly , Floh Alejandro , Kirsh Joel A. , Taylor Glenn , Thull-Freedman Jennifer
Published: November 2007

OBJECTIVE. The goal was to determine, in children with myocarditis, the frequency of various presenting symptoms and the sensitivity of clinical and laboratory investigations routinely available in the emergency department.

METHODS. We performed a retrospective review of all patients <18 years of age who were diagnosed as having myocarditis at our institution between May 2000 and May 2006 and who initially presented to an emergency department. Patients were categorized as having definite myocarditis (positive endomyocardial biopsy results) or probable myocarditis(diagnosis assigned by a pediatric cardiologist on the basis of history, physical examination, and investigation results in the absence of an endomyocardial biopsy or in the presence of negative biopsy results). All patients were assigned a predominant category of symptoms at presentation on the basis of criteria defined a priori.

RESULTS. There were 16 cases of definite myocarditis and 15 cases of probable myocarditis. The age distribution was nonnormal, with peaks among children ≤3 years and ≥16 years of age. Of 14 patients who were seen by a physician before being diagnosed with myocarditis, 57% were originally diagnosed as having pneumonia or asthma. Thirty-two percent of patients presented with predominantly respiratory symptoms, 29% had cardiac symptoms, and 6% had gastrointestinal symptoms. Although evidence of cardiac dysfunction was frequently present in the form of respiratory distress, only a minority of children had evidence of hepatomegaly or abnormal cardiac examination results. The sensitivities of electrocardiograms and chest radiographs as screening tests were 93% and 55%, respectively. Among laboratory tests studied, aspartate aminotransferase measurement was the most sensitive (sensitivity: 85%).

CONCLUSIONS. Children with myocarditis present with symptoms that can be mistaken for other types of illnesses; respiratory presentations were most common. When clinical suspicion of myocarditis exists, chest radiography alone is an insufficient screening test. All children should undergo electrocardiography. Aspartate aminotransferase testing may be a useful adjunctive investigation.
Assessment of Child and Adolescent Overweight and Obesity
Authors: Krebs Nancy F. , Himes John H. , Jacobson Dawn , Nicklas Theresa A. , Guilday Patricia , Styne Dennis
Published: November 2007

Accurate appropriate assessment of overweight and obesity in children and adolescents is a critical aspect of contemporary medical care. However, physicians and other health care professionals may find this a somewhat thorny field to enter. The BMI has become the standard as a reliable indicator of overweight and obesity. The BMI is incomplete, however, without consideration of the complex behavioral factors that influence obesity.Because of limited time and resources, clinicians need to have quick, evidence-based interventions that can help patients and their families recognize the importance of reducing overweight and obesity and take action. In an era of fast food, computers, and DVDs, it is not easy to persuade patients to modify their diets and to become more physically active. Because research concerning effective assessment of childhood obesity contains many gaps, this report is intended to provide a comprehensive approach to assessment and to present the evidence available to support key aspects of assessment. The discussion and recommendations are based on >300 studies published since 1995, which examined an array of assessment tools. With this information, clinicians should find themselves better equipped to face the challenges of assessing childhood overweight and obesity accurately.
Flow Preferences for Juvenile Robust Redhorses in an Experimental Mesocosm: Implications for Developing Sampling Protocols
Authors: Mosley Diarra L. , Jennings Cecil A.
Published: November 2007

The robust redhorse Moxostoma robustum, originally described by Edward Cope in 1870 from specimens collected from the Yadkin River, North Carolina, apparently went unnoticed until 1991 when it was rediscovered in the lower Oconee River, Georgia. Despite extensive surveys and an ongoing, decade-long restoration program, wild-spawned juveniles 30–410 mm in total length have not been collected. This project experimentally evaluated one hypothesis (flow class use) that seeks to explain the absence of juvenile robust redhorses from the catch. Two experimental mesocosms were used to determine whether juvenile robust redhorses use flow classes in proportion to their availability. Pond-reared juveniles were exposed to four flow-based habitat types (eddies = −0.12 to −0.01 m/s, slow flow = 0.00–0.15 m/s, moderate flow = 0.16–0.32 m/s, and backwaters) in four 10-d trials, in which 16 pond-reared test fish were used per trial, with replacement. Location data were recorded hourly during daytime hours for each fish in all trials and evaluated with a log-linear, chi-square model. In winter, test fish showed a preference for eddies and backwaters and avoided slow to moderate flows. In early spring, test fish showed a preference for eddies and avoided the moderate flows. Current field sampling for juvenile robust redhorses has not targeted the flow classes used by fish in this experiment; however, collection of wild-caught juveniles may be improved by sampling in eddies and their associated transitional areas.
An Evaluation of the Relative Influence of Spatial, Statistical, and Biological Factors on the Accuracy of Stream Fish Species Presence Models
Authors: Ruiz John C. , Peterson James T.
Published: November 2007

Models relating fish species presence to landscape and stream features are increasingly being used by natural resource managers. The accuracy of these models directly influences the ability to make sound stream management decisions. To evaluate the effect of biotic and abiotic factors on model accuracy, we fit parametric (logistic regression) and nonparametric (k‐nearest neighbor) models of species presence at two spatial scales using subwatershed and stream reach characteristics. We then evaluated the influence of model type, spatial scale, and species‐specific characteristics on species presence omission and commission errors for the best‐fitting scale‐specific parametric and nonparametric models (total of four per species). We found that error rates were higher within species than among species and varied among species by 3.9% (omission) and 8.7% (commission). Within‐species variation in error rates was primarily related to model type and spatial scale, whereas among‐species variation was due to the species‐specific characteristic‐habitat specialization. The relationship between these factors and the omission and commission error rates, however, were relatively complex. The k‐nearest neighbor models were generally more accurate (produced lower errors) at predicting species presence at larger, subwatershed scales, whereas the logistic regression models were more accurate at predicting species presence at smaller, stream reach scales. Similarly, commission error rates were lower for models predicting the presence of habitat generalists at larger scales, whereas commission error rates were lowest for models predicting the presence of habitat specialists at smaller, stream reach scales. The findings from this study suggest that species‐specific characteristics and spatial autocorrelation can influence the accuracy of species presence models and that biologists should consider these effects when modeling the presence or absence of fish species.
Current Treatment and Clinical Trial Developments for Ductal Carcinoma In Situ of the Breast
Authors: Boughey Judy C. , Gonzalez Ricardo J. , Bonner Everett , Kuerer Henry M.
Published: November 2007

Learning Objectives

After completing this course, the reader will be able to: Discuss the role of radiation therapy in the adjuvant treatment of DCIS.Describe the impact of tamoxifen in the treatment of DCIS.Discuss evolving strategies in neoadjuvant treatment for DCIS.

Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
First-Line Chemotherapy for HER-2–Negative Metastatic Breast Cancer Patients Who Received Anthracyclines as Adjuvant Treatment
Authors: Morabito Alessandro , Piccirillo Maria Carmela , Monaco Katia , Pacilio Carmen , Nuzzo Francesco , Chiodini Paolo , Gallo Ciro , Matteis Andrea , Perrone Francesco ,   for the NCI Naples Breast Cancer Group
Published: November 2007

Learning Objectives

After completing this course, the reader will be able to: Discuss the value of retreatment with anthracyclines for HER-2–negative metastatic breast cancer patients who received anthracyclines as adjuvant treatment.Discuss the role of liposomal anthracyclines, taxanes, and combinations without anthracyclines and taxanes, or innovative treatments, including target-based agents.Comment on the weakness and quality of available evidence.

Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Angiotensin-II acute regulation of rapid response genes in human, bovine, and rat adrenocortical cells
Authors: Nogueira Edson F , Vargas Claudia A , Otis Mélissa , Gallo-Payet Nicole , Bollag Wendy B , Rainey William E
Published: November 2007

Angiotensin-II (Ang-II) regulates adrenal steroid production and gene transcription through several signaling pathways. Changes in gene transcription occur within minutes after Ang-II stimulation, causing an increase in aldosterone production and subsequent increase in the overall capacity to produce aldosterone. Our goal was to compare the Ang-II regulation of early gene expression and confirm the up-regulation of selected genes using quantitative real-time RT-PCR (qPCR) across three species, such as, human, bovine, and rat. Microarray analyses were performed using samples from control and Ang-II (10 nM)-treated (1 h) cells from human adrenocortical tumor cell line H295R, and primary adrenal glomerulosa cells from bovine and rat, applied respectively to human, bovine, and rat chips. qPCR was performed to confirm up-regulation of selected genes using mRNA. The microarray comparison revealed 18% similarity among the top 50 up-regulated genes, with human/rat, 20%; human/bovine, 36%; and rat/bovine, 26% similarity. The gene list generated by this comparison included: activating transcription factor 3, B-cell translocation gene (BTG2), Nuclear receptor subfamily 4, group A, member 1 (NR4A1), NR4A2, NR4A3, early growth response 1, v-fos FBJ murine osteosarcoma viral oncogene homolog (c-FOS), FOSB, and Jun family member B (JUNB). Pretreatment of H295R cells with cycloheximide had no effect on Ang-II induction of these genes, suggesting that they are direct targets of Ang-II signaling. The Ang-II gene targets have been defined in three different adrenocortical model systems. Several of the listed genes have previously been described as being key regulators of adrenocortical function. The presence of adrenal cell common genes in such distinct cell models strengthens the hypothesis that these genes are regulators of aldosterone production.