bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the primary aetiology upon the clinical outcome of adults with childhood-onset GH deficiency
Authors: Hoybye Charlotte , Jönsson Peter , Monson John P , Kołtowska-Häggström Maria , Hána Václav , Geffner Mitchell , Abs Roger 
Published: November 2007

AbstractObjectiveThe impact of the aetiology of childhood-onset GH deficiency (CO-GHD) on the clinical presentation during adulthood and the response to GH replacement has been poorly defined. Our study aims to characterize CO-GHD in adults due to different aetiologies and evaluate the effect of 2 years of GH replacement therapy.Design and methodsData from 353 adults with CO-GHD from Pfizer International Metabolic Database KIMS were retrospectively grouped according to GHD aetiology: non-organic disorder (n=147), organic pituitary disease (n=159), and brain tumour (n=47). Extent of pituitary dysfunction, IGF-I concentration, lipid concentrations and quality-of-life (QoL) were assessed at baseline and after 2 years of GH replacement.ResultsGHD was diagnosed at a later age in the organic pituitary group than in the other groups, resulting in a shorter duration of GH treatment during childhood. However, the final height was greater in the organic pituitary group. Panhypopituitarism was most common in the non-organic disorder and in the organic pituitary groups, while isolated GHD was more prominent in the brain tumour group. Serum IGF-I levels were the lowest in the non-organic group. QoL was the poorest in the brain tumour group. Lipid profile and QoL improved significantly during GH replacement.ConclusionThe adverse consequences of CO-GHD in adulthood vary between aetiologies, but improve similarly with GH treatment. It is, therefore, important to consider retesting all patients with CO-GHD in early adulthood and, if persistent severe GHD is confirmed, recommence GH replacement.
Optimalization and cost management of lanreotide-Autogel therapy in acromegaly
Authors: Abrams Pascale , Alexopoulou Orsalia , Abs Roger , Maiter Dominique , Verhelst Johan 
Published: November 2007

AbstractBackgroundLanreotide-Autogel is a depot formulation of the somatostatin analog lanreotide used in the treatment of acromegaly. We investigated whether prolonging or shortening the interval between injections would offer any benefit.Subjects and methodsThe interval was prolonged from once every 4 weeks to once every 6 weeks when patients (n=9) had normal IGF-I and GH concentrations. When patients (n=12) had still elevated IGF-I or GH on the maximal dose of 120 mg every 4 weeks, the interval was shortened to once every 3 weeks. Serum IGF-I and GH were measured after 12 and 24 weeks to allow for dose adaptation. Symptoms and tumor volume were evaluated at baseline and after 36 weeks.ResultsIn seven of the nine subjects with normal IGF-I and GH, the interval could be extended to 6 weeks without loosing efficacy on IGF-I (195 vs 213 μg/l; not significant, NS) and GH concentrations (1.4 vs 1.3 μg/l; NS). The weekly dose could significantly be reduced (from 23.3 to 17.8 mg; P=0.002). In only 1 of the 12 not-controlled patients, reducing the interval to once every 3 weeks induced normalization of IGF-I and GH.ConclusionIn subjects whose acromegaly is well controlled using lanreotide-Autogel, prolonging the time interval between injections can often be increased 4 to 6 weeks without loss of efficacy, thereby improving the subject's comfort and reducing the cost of treatment. On the other hand, in subjects whose acromegaly is not controlled on a dose of 120 mg every 4 weeks, reducing the interval to every 3 weeks is rarely beneficial.
Beneficial effect of dose escalation of Octreotide-LAR as first-line therapy in patients with acromegaly
Authors: Colao Annamaria , Pivonello Rosario , Auriemma Renata S , Galdiero Mariano , Savastano Silvia , Lombardi Gaetano 
Published: November 2007

AbstractObjectiveTo evaluate the efficacy of dose escalation of Octreotide-long-acting repeatable (LAR) up to 40 mg/month we studied 56 newly diagnosed patients with acromegaly (24 women, 32 men; age 20–82 years).DesignAnalytical, observational, open and prospective.MethodsThree months after LAR treatment beginning with a dose of 20 mg /q28d (every 28 days), 24 patients maintained the same dose (Group A), while 32 required a dose of 30 mg/q28d (Group B). The dose was further increased to 40 mg/q28d in 17 out of the 32 patients of Group B for another 12 months (Group C).ResultsAfter 24 months, serum GH and IGF-I levels decreased by 93.1±8.6% (95% confidence limit (CL) 90.8–95.4%) and 62.7±13.4% (95% CL 59.1–66.3%) respectively. Control of GH and IGF-I levels was achieved in 45 patients (80.3%). Tumor shrinkage after 12 months was 49.8±23%; the relative tumor shrinkage during the second 12 months of treatment was 35.3±13.1% and overall tumor volume was 68.1±16.5% (95% CL 63.7–72.5%). Glucose tolerance impaired in eight patients (14.3%): four in Group A and four in Group C (16.7% vs 36.4%,P=0.39).The final dose was predicted by the patient's age at diagnosis (t=−2.2;P=0.032) and baseline tumor volume (t=2.1;P=0.043).ConclusionAn increase of the LAR dose up to 40 mg/q28d in patients resistant to 30 mg/q28d is followed by greater suppression of GH and IGF-I levels and tumor shrinkage without further significant impairment of glucose tolerance when compared with lower doses. These results suggest that a new dosage schedule of 40 mg every 28 days is applied in patients with acromegaly mostly of young age and with bigger tumors who are likely to be poorly responsive to standard doses of Octreotide-LAR.
Polymorphisms in the interleukin-6 receptor gene are associated with bone mineral density and body mass index in Spanish postmenopausal women
Authors: Bustamante M , Nogués X , Mellibovsky L , Agueda L , Jurado S , Cáceres E , Blanch J , Carreras R , Díez-Pérez A , Grinberg D , Balcells S 
Published: November 2007

AbstractObjectiveOsteoporosis and obesity are complex diseases with a strong genetic component. Bone mineral density (BMD) and body mass index (BMI) linkage studies identified a locus at 1q21-23, where the interleukin-6 receptor (IL6R) gene is located. The IL6R and the gp130 receptors are the mediators of IL6 action. Serum levels of IL6 and sIL6R (the soluble form of IL6R) are higher in several diseases such as osteoporosis or obesity. Variants atIL6Rhave been associated with BMI and obesity. However,IL6Ris an as-yet-unexplored osteoporosis candidate gene.DesignIn the present study we analysed two polymorphisms in theIL6Rpromoter, −1435 C/T (rs3887104) and −208 G/A (rs4845617), and the Asp358Ala polymorphism (rs8192284), in relation to both BMD and BMI in a cohort of 559 postmenopausal Spanish women.ResultsThe promoter polymorphisms, −1435 C/T and −208 G/A were associated with femoral neck (FN) BMD (P=0.011 andP=0.025 respectively). The C-A and T-G promoter haplotypes were also associated with FN BMD. Additionally, the Asp358Ala variant was associated with lumbar spine BMD (P=0.038). Finally, the −208 G/A polymorphism and the C-G and C-A haplotypes were associated with BMI and obesity, where GG was the risk genotype (P=0.033 for BMI;P=0.010 for obesity).ConclusionThese data suggest that variants in theIL6Rgene are not only involved in the determination of BMI but also relevant for the determination of BMD. TheIL6Rgene may belong to the growing list of genes known to be involved in both phenotypes.
Evaluation of insulin resistance in a cohort of HIV-infected youth
Authors: Rosso Raffaella , Parodi Arianna , d'Annunzio Giuseppe , Ginocchio Francesca , Nicolini Laura , Torrisi Chiara , Pia Sormani Maria , Lorini Renata , Viscoli Claudio , Vignolo Marina 
Published: November 2007

AbstractObjectiveMetabolic abnormalities, including impairment of glucose homeostasis, have been well characterized in HIV-infected patients. In contrast to adults, insulin resistance and diabetes mellitus appear to be relatively uncommon finding in youth.DesignWe assessed insulin resistance, and associated risk factors, in a population of vertically HIV-infected children and young adults, when compared with a control population of healthy children.MethodsAt the time of enrolment, weeks of pregnancy, birth weight, sex, age, weight, height, body mass index (BMI), pubertal stages, CDC classification, blood pressure, clinical lipodystrophy, hepatitis B or C co-infection, antiretroviral therapy, CD4 T lymphocyte counts, and HIV-RNA levels were recorded. Fasting plasma glucose and insulin levels and homeostatic model assessment-insulin resistance (HOMA-IR) were determined. These parameters were compared between HIV patients and healthy controls with multivariate analyses.ResultsFasting insulin levels (OR=1.21,P<0.001) and glycemia (OR=0.89,P<0.001) were significantly different between HIV-infected patients and controls. Antiretroviral therapy duration (r=0.281,P<0.05), triglyceride levels (r=0.286,P<0.05), age (r=0.299,P<0.05), and BMI SDS (r=0.485,P<0.001) were significant predictor variables of insulin resistance, expressed as HOMA-IR. Moreover, clinical lipodystrophy seems to be strongly correlated to glycemia (P<0.05), triglyceride levels (P<0.05), serum insulin levels (P<0.001), HOMA-IR (P<0.05), and also with therapy duration (P<0.05).ConclusionsBoth HIV infection and antiretroviral therapy demonstrate differential effects on glucose metabolism in HIV-infected children. Targeted prevention of insulin resistance and diabetes mellitus in HIV-infected children and young adults is needed in order to avoid the associated long-term complications that would otherwise occur, given the improvement in life expectancy of HIV-infected individuals.
Guidelines for Adolescent Depression in Primary Care (GLAD-PC): II. Treatment and Ongoing Management
Authors: Cheung Amy H. , Zuckerbrot Rachel A. , Jensen Peter S. , Ghalib Kareem , Laraque Danielle , Stein Ruth E.K. ,   and the GLAD-PC Steering Group
Published: November 2007

OBJECTIVES. To develop clinical practice guidelines to assist primary care clinicians in the management of adolescent depression. This second part of the guidelines addresses treatment and ongoing management of adolescent depression in the primary care setting.METHODS. Using a combination of evidence- and consensus-based methodologies, guidelines were developed in 5 phases as informed by (1) current scientific evidence (published and unpublished), (2) a series of focus groups, (3) a formal survey, (4) an expert consensus workshop, and (5) revision and iteration among members of the steering committee.RESULTS. These guidelines are targeted for youth aged 10 to 21 years and offer recommendations for the management of adolescent depression in primary care, including (1) active monitoring of mildly depressed youth, (2) details for the specific application of evidence-based medication and psychotherapeutic approaches in cases of moderate-to-severe depression, (3) careful monitoring of adverse effects, (4) consultation and coordination of care with mental health specialists, (5) ongoing tracking of outcomes, and (6) specific steps to be taken in instances of partial or no improvement after an initial treatment has begun. The strength of each recommendation and its evidence base are summarized.CONCLUSIONS. These guidelines cannot replace clinical judgment, and they should not be the sole source of guidance for adolescent depression management. Nonetheless, the guidelines may assist primary care clinicians in the management of depressed adolescents in an era of great clinical need and a shortage of mental health specialists. Additional research concerning the management of youth with depression in primary care is needed, including the usability, feasibility, and sustainability of guidelines and determination of the extent to which the guidelines actually improve outcomes of youth with depression.
Altered Resting Cerebral Blood Flow in Adolescents With in Utero Cocaine Exposure Revealed by Perfusion Functional MRI
Authors: Rao Hengyi , Wang Jiongjiong , Giannetta Joan , Korczykowski Marc , Shera David , Avants Brian B. , Gee James , Detre John A. , Hurt Hallam 
Published: November 2007

OBJECTIVES. Animal studies have clearly demonstrated the effects of in utero cocaine exposure on neural ontogeny, especially in dopamine-rich areas of cerebral cortex; however, less is known about how in utero cocaine exposure affects longitudinal neurocognitive development of the human brain. We used continuous arterial spin-labeling perfusion functional MRI to measure the effect of in utero cocaine exposure on resting brain function by comparing resting cerebral blood flow of cocaine-exposed adolescents with non–cocaine-exposed control subjects.
PATIENTS AND METHODS. Twenty-four cocaine-exposed adolescents and 25 matched non–cocaine-exposed control subjects underwent structural and perfusion functional MRI during resting states. Direct subtraction, voxel-wise general linear modeling, and region-of-interest analyses were performed on the cerebral blood flow images to compare the resting cerebral blood flow between the 2 groups.
RESULTS. Compared with control subjects, cocaine-exposed adolescents showed significantly reduced global cerebral blood flow. The decrease of cerebral blood flow in cocaine-exposed adolescents was observed mainly in posterior and inferior brain regions, including the occipital cortex and thalamus. After adjusting for global cerebral blood flow, however, a significant increase in relative cerebral blood flow in cocaine-exposed adolescents was found in anterior and superior brain regions, including the prefrontal, cingulate, insular, amygdala, and superior parietal cortex. Furthermore, the functional modulations by in utero cocaine exposure on all of these regions except amygdala cannot be accounted for by the variation in brain anatomy.
CONCLUSIONS. In utero cocaine exposure may reduce global cerebral blood flow, and this reduction may persist into adolescence. The relative increase of cerebral blood flow in anterior and superior brain regions in cocaine-exposed adolescent participants suggests that compensatory mechanisms for reduced global cerebral blood flow may develop during neural ontogeny. Arterial spin-labeling perfusion MRI may be a valuable tool for investigating the long-term effects of in utero drug exposure.
Impact of Size at Birth on the Microvasculature: The Avon Longitudinal Study of Parents and Children
Authors: Tapp Robyn J. , Williams Cathy , Witt Nicholas , Chaturvedi Nish , Evans Richard , Thom Simon A. McG , Hughes Alun D. , Ness Andrew 
Published: November 2007

BACKGROUND. The impact of early life factors on the microvasculature is relatively unknown.
OBJECTIVES. We hypothesized that small birth size may be associated with structural variations in the retinal vasculature in children.
METHODS. The Avon Longitudinal Study of Parents and Children followed a cohort of children born in 1991–1992 from birth. The current study included the first 263 children who were systematically screened in the year-12 follow-up. Complete data were available for 166 children with a gestation of ≥37 weeks. Retinal circulatory measures were evaluated, including retinal microvascular tortuosity and bifurcation optimality deviance, an indicator of abnormal endothelial function.
RESULTS. Optimality deviance and retinal tortuosity were higher among those with lower birth weight. Linear regression modeling was used to assess the association of retinal microvascular measures with birth weight. The standardized β coefficient between optimality deviance and birth weight was −.182 adjusted for gender and age in weeks; additional adjustment for systolic blood pressure and heart rate had little impact on the β coefficient. A similar association was observed for retinal tortuosity.
CONCLUSION. The findings of this study suggest that early life factors may have an important impact on retinal vascular structure, possibly through an adverse effect on endothelial function.
Burden of Acute Sore Throat and Group A Streptococcal Pharyngitis in School-aged Children and Their Families in Australia
Authors: Danchin Margaret H. , Rogers Susan , Kelpie Loraine , Selvaraj Gowri , Curtis Nigel , Carlin John B. , Nolan Terence M. , Carapetis Jonathan R. 
Published: November 2007

OBJECTIVE. The objective of this study was to determine the incidence, transmission, carriage, and risk factors for group A streptococcal pharyngitis in school-aged children and their families.
METHODS. A 16-month, prospective, family-based cohort study was undertaken from August 2001 through December 2002 in Melbourne, Australia. A total of 202 families (853 people) with at least 1 child aged 3 to 12 years were randomly selected from 3 primary care practices across suburban Melbourne to collect surveillance data for acute group A streptococcal pharyngitis, including serology for index and secondary cases and intermittent carriage data. Cohort retention was 97% for 16 months.
RESULTS. The incidence of acute sore throat, group A streptococcal swab–positive pharyngitis, and serologically confirmed group A streptococcal pharyngitis was 33, 13, and 8 per 100 child-years, respectively, for school-aged children (5–12 years) and 60, 20, and 15 per 100 family-years, respectively. Sore throat was less common in adults than children, but adults with sore throat were as likely as children to have group A streptococcal culture–positive or serologically proven pharyngitis. In families who had a primary case, 43% had at least 1 secondary case, and in family members who were at risk, 13% contracted a secondary case. The spring, summer, and winter carriage rates for children were 13%, 8%, and 16%, respectively, and for adults the rate was 2% across all seasons.
CONCLUSIONS. Group A streptococcal pharyngitis is still common, and the peak incidence occurs in school-aged children. However, the incidence in adults is higher than expected, and the number of secondary cases in families may be an important factor when considering the potential benefits of treatment.
Is Childhood Vaccination Associated With Asthma? A Meta-analysis of Observational Studies
Authors: Balicer Ran D. , Grotto Itamar , Mimouni Marc , Mimouni Daniel 
Published: November 2007

BACKGROUND. The possible link between immunization and atopic diseases has been under intense debate in the last decade.
OBJECTIVE. The aim of this study was to systematically review the available evidence on the association of whole-cell pertussis and BCG vaccination with the risk of asthma in childhood and adolescence.
METHODS. The major medical electronic databases (Medline, National Library of Medicine Gateway, and Cochrane Library) were searched, and reference lists of the relevant publications were reviewed for relevant birth-cohort studies and randomized, controlled trials from 1966 to March 2006. Only studies that directly compared vaccinated and unvaccinated children, validated vaccination status by medical charts, and used preset criteria to define asthma were included. Data were abstracted by using a standardized protocol and computerized report form. Results were analyzed by applying a fixed-effect or random-effect model, according to the heterogeneity of the studies. Sensitivity analyses by scoring criteria were performed.
RESULTS. Seven studies of pertussis vaccination (with a total of 186663 patients) and 5 studies of BCG vaccination (with a total of 41479 patients) met our inclusion criteria. No statistically significant association was detected between either whole-cell pertussis or BCG vaccination and incidence rates of asthma during childhood and adolescence. This lack of a significant association proved to be robust on sensitivity analyses for BCG but not for pertussis vaccine.
CONCLUSIONS. Currently available data, based on observational studies, do not support an association, provocative or protective, between receipt of the BCG or whole-cell pertussis vaccine and risk of asthma in childhood and adolescence.
Health Status and Health-Related Quality of Life Preference-Based Outcomes of Children Who Are Aged 7 to 9 Years and Have Bilateral Permanent Childhood Hearing Impairment
Authors: Petrou Stavros , McCann Donna , Law Catherine M. , Watkin Peter M. , Worsfold Sarah , Kennedy Colin R. 
Published: November 2007

OBJECTIVE. The objective of this study was to describe the health status and health-related quality of life preference-based outcomes of children with diagnosed bilateral permanent childhood hearing impairment and a comparison group of English-speaking children with normal hearing.
METHODS. We studied 120 children who were aged 7 to 9 years and had bilateral permanent childhood hearing impairment of moderate or greater severity, identified from a cohort of 156733 children who were born in 8 districts of southern England, and 63 English-speaking children with normal hearing and the same place of birth and age at assessment. Principal caregivers were interviewed by using the Health Utilities Index Mark III questionnaire for proxy-assessed usual health status assessment. Levels of function within each of the 8 attributes of the Health Utilities Index Mark III (cognition, vision, hearing, speech, ambulation, dexterity, emotion, and pain) were recorded.
RESULTS. Bilateral permanent childhood hearing impairment is associated with significantly increased proportions of suboptimal levels of function and significantly lower single-attribute utility scores in 6 of the 8 attributes of the Health Utilities Index Mark III: vision, hearing, speech, ambulation, dexterity, and cognition. Compared with the children with normal hearing, the mean multiattribute utility score for the children with hearing impairment was significantly lower for both the whole group and the moderate, severe, and profound severity subgroups. The differences in the distributions of the multiattribute utility scores between the children with hearing impairment as a group and the children with normal hearing and between each of the severity subgroups and the children with normal hearing all were statistically significant.
CONCLUSIONS. This study provides rigorous evidence of an association between bilateral permanent childhood hearing impairment and diminished health status and health-related quality of life preference-based outcomes during midchildhood.