bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gonadotrophic status in adolescents with pituitary stalk interruption syndrome
Authors: Rottembourg Diane , Linglart Agnès , Adamsbaum Catherine , Lahlou Najiba , Teinturier Cécile , Bougnères Pierre , Carel Jean‐Claude 
Published: June 2008

SummaryObjective  Pituitary stalk interruption syndrome (PSIS) is a frequent cause of GH deficiency (GHD) and is commonly associated with other PH deficiencies (PHDs). Although previous reports have correlated multiple PHDs with severe anatomical lesions, the status of the gonadotrophic axis has not yet been thoroughly analysed.Methods  We retrospectively reviewed the medical records of 27 patients (15 males, 12 females) with GHD and PSIS defined by MRI findings. The status of the gonadotrophic axis was evaluated in children who were at least 14·5 years (boys) or 13 years (girls).Results  Out of 27 patients, five displayed spontaneous full pubertal development with normal hormonal values at the final evaluation, whereas 22 of 27 patients (81%) had complete (n = 18) or partial pubertal deficiency. Three girls had primary amenorrhoea with normal gonadotrophin values, raising the possibility of subtle disturbances of gonadotrophin pulsatility. Of the 21 patients with TSH or ACTH deficiency, 17 (81%) had complete gonadotrophin deficiency. Two of our six patients with apparently isolated GHD during childhood had gonadotrophin deficiency. Cryptorchidism was present at birth in six boys (40%). Of these six boys, one had normal pubertal development. Ten of 11 boys with micropenis at birth had gonadotrophin deficiency.Conclusions  Gonadotrophin deficiency is a common finding in adolescents with PSIS and is frequently associated with other PHDs. However its severity is variable, ranging from complete gonadotrophin deficiency to normogonadotrophic amenorrhoea. The occurrence of gonadotrophin deficiency in 33% of children with apparently isolated GHD and PSIS has important implications for the counselling and follow‐up of these patients.
Long‐term treatment of familial male‐limited precocious puberty (testotoxicosis) with cyproterone acetate or ketoconazole
Authors: Almeida Madson Queiroz , Brito Vinicius Nahime , Lins Thereza Selma S. , Guerra‐Junior Gil , De Castro Margaret , Antonini Sonir Roberto , Arnhold Ivo Jorge Prado , Mendonca Berenice Bilharinho , Latronico Ana Claudia 
Published: June 2008

SummaryBackground Familial male‐limited precocious puberty (FMPP) or testotoxicosis is a rare gonadotrophin‐independent form of sexual precocity caused by constitutively activating mutations of the LH receptor. Several clinical therapeutic approaches have been reported for this disorder, but with a paucity of long‐term outcome data.Objective To evaluate the long‐term treatment of testotoxicosis with cyproterone acetate or ketoconazole.Design A multicentric retrospective clinical study.Patients Ten boys from eight unrelated Brazilian families who carried known LH‐receptor activating mutations were treated with 70 mg/m2cyproterone acetate (n = 5) or 10 mg/kg ketoconazole (n = 5) for a mean period of 5 and 8 years, respectively.Measurements Chronological and bone ages, bone age/chronological age ratio, target height (TH) range, adult height, basal and GnRH‐stimulated gonadotrophin levels and basal testosterone levels were assessed.Results Growth velocity decreased significantly during treatment with cyproterone acetate or ketoconazole when compared to pretreatment value in each group (P < 0·05). Bone age/chronological age ratio decreased significantly after cyproterone acetate or ketoconazole therapy. Basal testosterone levels were significantly lower in patients undergoing ketoconazole compared to cyproterone acetate treatment [0·6 ± 0·3 nmol/l (42 ± 21 ng/dl)vs.5·6 ± 4·0 nmol/l (392 ± 280 ng/dl);P < 0·05], as expected. Secondary gonadotrophin‐dependent precocious puberty occurred at a similar frequency (40%) in both groups. Five patients have attained adult height and two patients have already reached 90% of their adult height. Two of them achieved their TH range and one patient, for whom TH was not available, had an adult height of 0·3 SDS. Four boys (two in each group) did not attain their TH range.Conclusion Long‐term treatment with cyproterone acetate or ketoconazole resulted in similar outcomes without important side‐effects in boys with testotoxicosis. However, both therapies showed limited efficacy in attaining normal adult height.
Previous radiotherapy negatively influences quality of life during 4 years of follow‐up in patients cured from acromegaly
Authors: Van Der Klaauw Agatha A. , Biermasz Nienke R. , Hoftijzer Hendrieke C. , Pereira Alberto M. , Romijn Johannes A. 
Published: June 2008

SummaryObjective  Cross‐sectional studies have shown impaired quality of life (QoL) in patients in biochemical control of acromegaly. The aim of this study was to assess longitudinal changes in QoL in a homogenous cohort of patients with sustained biochemical control of acromegaly.Design  Prospective follow‐up study.Patients and methods  QoL was assessed using four health‐related QoL questionnaires (HADS, Hospital Anxiety and Depression Scale; MFI‐20, Multidimensional Fatigue Index; NHP, Nottingham Health Profile; and SF‐36, Short Form‐36) and one disease‐specific acromegaly quality of life (ACRO‐QOL) questionnaire in 82 patients (43 men) with strict biochemical control of acromegaly, aged 56 years (range 29–84 years) at baseline and after 4 years of follow‐up. The mean duration of controlled disease was 12 years (range 1–26 years).Results  During follow‐up, scores in 5 of 26 QoL subscales significantly worsened: physical and social functioning (SF‐36), physical fatigue (MFI‐20), and psychological well‐being and personal relations (ACRO‐QOL). Using linear regression analysis, baseline item scores predicted the follow‐up scores, indicating individual stability over time. Previous radiotherapy (n = 27, 33%) negatively influenced several QoL subscales at follow‐up: energy, pain and social isolation (NHP), physical fatigue and reduction in activity and motivation (MFI‐20), depression and total anxiety and depression scores (HADS) and physical performance (ACRO‐QOL).Conclusion  During 4 years of follow‐up in patients with long‐term biochemical control of ACRO‐QOL is subtly, but progressively impaired. Radiotherapy was the predominant indicator of progressive impairment in QoL.
Polymorphisms of the ghrelin/obestatin gene and ghrelin levels in Chinese children with short stature
Authors: Zou Chao Chun , Huang Ke , Liang Li , Zhao Zheng Yan 
Published: June 2008

SummaryObjective  To investigate the role of ghrelin and polymorphisms of ghrelin/obestatin gene in children with short stature.Methods  A total of 117 GH deficient (GHD) and 81 idiopathic short stature (ISS) children were studied. The controls consisted of 125 age and gender‐matched healthy children. The Arg51Gln, Leu72Met and Gln90Leu polymorphisms were genotyped using MassArray and total plasma ghrelin was measured by radioimmunoassay.Results  In this study, the frequency of the Arg51Gln polymorphism was very low (0% in controls and 1·0% in patients). The frequency of the Gln90Leu polymorphism was 1·6% in controls and 0·5% in patients, respectively. Higher frequencies of Leu72Met (34·4% in controls and 39·9% in patients) and Met72Met genotypes (4·0% in controls and 2·0% in patients) were found. The differences in the Arg51Gln, Leu72Met or Gln90Leu genotypes and allele frequencies between patients and controls were not significant. Also, there were no significant differences in the Leu72Met genotypes and allele frequencies between GHD and ISS subgroups. There were no significant differences in clinical characteristics and biochemistry markers (including ghrelin levels) among the different genotypes of Leu72Met. However, plasma ghrelin levels in the GHD group were significantly lower than those of controls (P = 0·001).Conclusion  These results suggest that ghrelin may have a role in GH secretion and controlling growth. Lower ghrelin levels, but not ghrelin/obestatin polymorphism, might contribute to GHD.
A novel therapeutic paradigm to treat congenital hypothyroidism
Authors: Mathai Sarah , Cutfield Wayne S. , Gunn Alistair J. , Webster Dianne , Jefferies Craig , Robinson Elizabeth , Hofman Paul 
Published: June 2008

SummaryObjective  To determine the effectiveness of a novel therapeutic paradigm to treat congenital hypothyroidism (CH) incorporating variable initial doses of L‐T4 based on the underlying aetiology and frequent monitoring, up to 2 years of age.Design  Retrospective cohort study.Patients  Infants with primary CH diagnosed by newborn screening.Measurements  Treatment with L‐T4 suspension initiated at 10, 12 and 15 µg/kg/day for dyshormonogenesis, ectopia and athyreosis, respectively. Serum TSH and free T4 (FT4) levels monitored weekly during the first 4 weeks, at 6 weeks, thereafter monthly during the first 2 years. Dose changes were made to keep FT4 level in upper half of the normal range.Results  Sixty‐nine infants; 17 had dyshormonogenesis, 35 ectopia and 17 athyreosis. Seventy‐eight percent of subjects normalized FT4 levels within 7 days of treatment and 100% within 14 days. TSH levels normalized in 26% of infants within 7 days and in 92% by 21 days. Supraphysiological levels of FT4 were noted in 28% of infants, for a maximum of 2 weeks. 48% infants needed one dose adjustment and 30% needed at least two in the first month. In 52 infants over the first 2 years, mean FT4 levels were consistently in the upper half of the normal range. Two or more dose adjustments every 3 months were made 57 times in the first year as compared to 19 times in the second year.Conclusions  A variable initial dose paradigm based on aetiology with frequent testing and using T4 suspension rapidly normalizes FT4 levels without producing persistent hyperthyroxinaemia.
Heritability of blood concentrations of sex‐steroids in relation to body composition in young adult male siblings
Authors: Bogaert Veerle , Taes Youri , Konings Peter , Van Steen Kristel , De Bacquer Dirk , Goemaere Stefan , Zmierczak Hans , Crabbe Patricia , Kaufman Jean‐Marc 
Published: June 2008

SummaryObjective  Sex steroid concentrations in men are related to body composition and both are determined by genetic and environmental factors. This study investigates heritability estimates of sex steroid serum concentrations and body composition as well as the genetic and environmental components of their interrelation.Patients  Six hundred and seventy‐four men (25–45 years) were included in this study with 274 independent pairs of brothers.Measurements  Body composition and regional fat mass estimates were determined using dual‐energy X‐ray absorptiometry. Serum testosterone (T), SHBG, oestradiol (E2) and LH levels were determined by immunoassay; free T and E2 levels were calculated.Results  Both sex steroid hormone concentrations and indices of body composition exhibited significant heritability estimates. Among sex steroid hormones, T had the highest heritability (h2 = 0·65), followed by free T (h2 = 0·54). A heritability of 0·73 was observed for SHBG; a heritability estimate of 0·83 was obtained for body weight. Significant genetic correlations were found between whole body fat mass and serum T (ρG = –0·46), free T (ρG = –0·27) and SHBG (ρG = –0·48) concentrations. No genetic relationship was observed between total (F) E2 or LH concentrations, respectively, and body composition.Conclusion  Both sex steroid serum levels and body composition are under strong genetic control. Their interrelation is in part underlied by a genetic correlation, indicative of the action of shared genes.
Primary cell cultures from anaplastic thyroid cancer obtained by fine‐needle aspiration used for chemosensitivity tests
Authors: Antonelli Alessandro , Ferrari Silvia Martina , Fallahi Poupak , Berti Piero , Materazzi Gabriele , Barani Lucio , Marchetti Ivo , Ferrannini Ele , Miccoli Paolo 
Published: June 2008

SummaryObjective  Anaplastic thyroid cancer (ATC) is often inoperable and chemotherapy and radiotherapy are the main treatments. Until now, ‘primary ATC cell cultures’ (ANA) have been developed from surgical biopsies. We investigated the possibility of obtaining ANA from fine‐needle aspiration (FNA‐ANA) and testing their sensitivity to chemotherapeutic agents, which could enable treatments to be more effective and avoid unnecessary surgical procedures.Design and patients  The aim of this study was to obtain FNA‐ANA from three ATC patients and to evaluate the chemosensitivity of FNA‐ANA to chemotherapeutic agents.Measurements and results  FNA‐ANA from ATC patients were cultured in RPMI 1640 and propagated in Dulbecco's modified Eagle's medium (DMEM). Chemosensitivity was evaluated by inhibiting the proliferation (analysing the number of viable cells by the cleavage of tetrazolium salts), by increasing the concentration of four different chemotherapeutic agents: bleomycin, cisplatin, gemcitabine and etoposide. The chemotherapeutic agents significantly inhibited (> 50%) FNA‐ANA proliferation. Another ANA for each patient was obtained from a surgical biopsy specimen; the results for the chemosensitivity tests were similar to those obtained using FNA‐ANA.Conclusions  Our study demonstrates the possibility of obtaining FNA‐ANA, and opens the way to the use of FNA‐ANA as a means of testing the chemosensitivity to different chemotherapeutic agents (and possibly the radiosensitivity) in each patient, avoiding unnecessary surgical procedures and the administration of inactive chemotherapeutics.
The role of cervical cytology and colposcopy in detecting cervical glandular neoplasia
Authors: Ullal A. , Roberts M. , Bulmer J. N. , Mathers M. E. , Wadehra V. 
Published: June 2008

Objective:  To determine the role of cervical cytology and colposcopy in the management of endocervical neoplasia.Setting:  Colposcopy unit and cytology laboratory in a teaching hospital.Sample:  Group 1 included 184 smears showing endocervical glandular neoplasia from 129 patients and group 2 included 101 patients with histology showing endocervical abnormalities in a 6‐year period (1993–1998). Follow‐up of 6–11 years to 2004 was available.Methods:  Group 1 were identified from the cytology computer records. Group 2 were identified from histology records on the cytology database and a record of histology cases kept for audit purposes. The clinical records were examined retrospectively.Results:  The positive predictive value (PPV) of abnormal endocervical cells in smears was 81.1% for significant glandular/squamous [cervical glandular intraepithelial neoplasia (CGIN)/cervical intraepithelial neoplasia grade2 (CIN2 or worse)] lesions. The PPV of colposcopy was 93.5% for significant glandular/squamous lesions of the cervix. The postcolposcopy probability of a significant lesion when colposcopy was normal was 87.5%. The sensitivity of colposcopy in detecting endocervical lesions was 9.8%. The sensitivity of cervical smears in detecting a significant endocervical abnormality (CGIN or worse) was 66.3%. The false negative rate for cytology of endocervical glandular lesions was 4.0%.Conclusions:  Endocervical glandular neoplasia detected on cytology is predictive of significant cervical pathology even when colposcopy is normal, which supports excisional biopsy in the primary assessment of these smears. The high concomitant squamous abnormality rate justifies the use of colposcopy to direct biopsies from the ectocervix. Cervical cytology is the only current screening method for cervical glandular abnormalities but sensitivity is poor.
Pathological features of colorectal carcinomas in MYH‐associated polyposis
Authors: O’Shea A M , Cleary S P , Croitoru M A , Kim H , Berk T , Monga N , Riddell R H , Pollett A , Gallinger S 
Published: June 2008

Aims:  MYH is a DNA glycosylase in the base excision repair pathway. Germ‐line biallelic mutations in the MYH gene are associated with the development of multiple colorectal adenomas and colorectal carcinoma (CRC). A slightly increased risk of CRC is suggested in monoallelic MYH mutation carriers. The aim was to characterize the histopathological features of carcinomas from biallelics and monoallelics.Methods and results:  Clinicopathological features of 57 colorectal carcinomas from 50 patients identified in familial CRC registries were recorded. These included 16 cancers from 14 MYH biallelics; 25 cancers from 22 MYH monoallelics; and 16 cancers from 14 controls. Carcinomas in biallelics demonstrated tubular, papillary or cribriform patterns as the predominant histological subtype, and main histological groups differed according to mutation status (P = 0.0053). All biallelic cancers were low grade, with high‐grade tumours more common in monoallelics and controls (P = 0.002). Synchronous polyps were observed in 75% of biallelics, 33% of monoallelics and 43% of controls (P = 0.035). Serrated carcinoma was the predominant type in 12% (3/25) of the monoallelics but in none of the biallelics or controls. MYH immunohistochemistry failed to distinguish between groups.Conclusions:  Neither pathological features nor immunohistochemistry could predict the MYH mutation status of CRCs in this study.
Expression profiles of matrix metalloproteinase 9 in teleost fish provide evidence for its active role in initiation and resolution of inflammation
Authors: Chadzinska Magdalena , Baginski Pawel , Kolaczkowska Elzbieta , Savelkoul Huub F. J. , Lidy Verburg‐van Kemenade B. M. 
Published: June 2008

SummaryMatrix metalloproteinase 9 (MMP‐9) belongs to a family of zinc‐dependent endopeptidases. As a consequence of its ability to cleave structural extracellular matrix molecules, mammalian MMP‐9 is associated with vital inflammatory processes such as leucocyte migration and tissue remodelling and regeneration. Interestingly, MMP‐9 genes have been identified in fish, but functional data are still limited and focus on the involvement of MMP‐9 in embryonic development, reproduction and post‐mortem tenderization. Here, we describe the involvement of MMP‐9 in the innate immunity of carp. In carp, MMP‐9 was most notably expressed in classical fish immune organs and in peritoneal and peripheral blood leucocytes, indicating a role of MMP‐9 in immune responses. In our well‐characterized zymosan‐induced peritonitis model for carp, we analysed expression of the MMP‐9 gene and the gelatinolytic levels of both pro‐ and activated forms of MMP‐9. The biphasic profile of MMP‐9 mRNA expression indicated involvement during the initial phase of inflammation and during the later phase of tissue remodelling. Also, in vitro stimulation of carp phagocytes with lipopolysaccharide or concanavalin A increased MMP‐9 gene expression, with a peak at 24 hr. The increase of MMP‐9 mRNA correlated with the peak of MMP‐9 gelatinolytic level in culture supernatants. These results provide evidence for an evolutionarily conserved and relevant role of MMP‐9 in the innate immune response.
Depletion of CD8+ T cells enhances airway remodelling in a rodent model of asthma
Authors: Tsuchiya Kimitake , Isogai Susumu , Tamaoka Meiyo , Inase Naohiko , Akashi Takumi , Martin James G. , Yoshizawa Yasuyuki 
Published: June 2008

SummaryAirway remodelling is induced by persistent airway inflammation and may lead to severe asthma. T cells play a pivotal role in asthmatic airway inflammation but their role in remodelling is poorly understood. Although previous studies have revealed that CD8+ T cells inhibit the late airway response and airway inflammation in a rat model of asthma, their effects on airway remodelling have not been evaluated. The aim of this study was to examine the role of CD8+ T cells in airway remodelling. Brown Norway rats were sensitized with ovalbumin (OVA) on day 0. CD8+ T cells in rats were depleted during the repeated challenges by treating them with a CD8α monoclonal antibody (OX‐8). Control rats were treated with mouse ascites. Sensitized rats were challenged with OVA on days 14, 19 and 24 or were sham challenged with phosphate‐buffered saline. On day 29, bronchoalveolar lavage and lung tissues were harvested. Repeated OVA inhalations evoked significant increases in the numbers of periodic acid–Schiff‐positive epithelial cells and proliferating cell nuclear antigen‐positive epithelial cells, and in airway smooth muscle mass compared to the control group. CD8‐depleted rats had significant enhancement of these changes, principally affecting the large airways. These results suggest that endogenous CD8+ T cells have inhibitory effects on airway remodelling in this model of asthma.
Targeting the chemotactic function of CD147 reduces collagen‐induced arthritis
Authors: Damsker Jesse M. , Okwumabua Ifeanyi , Pushkarsky Tatiana , Arora Kamalpreet , Bukrinsky Michael I. , Constant Stephanie L. 
Published: June 2008

SummaryCD147 is a type I transmembrane glycoprotein expressed on a wide variety of cell types, including all leucocytes. While CD147 is best known as a potent inducer of matrix metalloproteinases, it can also function as a regulator of leucocyte migration through its cell surface interaction with chemotactic extracellular cyclophilins. A potential role for CD147–cyclophilin interactions during inflammatory diseases, including rheumatoid arthritis (RA), is suggested from several studies. For example, CD147 expression is increased on reactive leucocytes in the synovial fluid and tissues of patients with arthritis. In addition, the synovial fluid of patients with RA contains high levels of extracellular cyclophilin A. In the current studies we investigated the contribution of the chemotactic function of CD147–cyclophilin interactions to joint inflammation using the mouse model of collagen‐induced arthritis. Our data demonstrate that proinflammatory leucocytes, specifically neutrophils, monocytes and activated CD4+ T cells, lose their ability to migrate in response to cyclophilin A in vitro when treated with anti‐CD147 monoclonal antibody. Furthermore, in vivo treatment with anti‐CD147 monoclonal antibody can reduce the development of collagen‐induced arthritis in mice by > 75%. Such findings suggest that CD147–cyclophilin interactions might contribute to the pathogenesis of RA by promoting the recruitment of leucocytes into joint tissues.
Span of management: concept analysis
Authors: Meyer Raquel M. 
Published: June 2008

AbstractTitle.  Span of management: concept analysis Aim.  This paper is a report of a concept analysis of span of management.Background.  Span of management is an important structural variable in evaluating the contributions of nursing managers to healthcare systems. Span of management is typically measured as a ratio. A wide variety of operational definitions have been applied and these differences have not been reconciled.Data sources.  A search of CINAHL, PsychINFO and Business Source Premier was completed in 2007 using the terms span of management, span of control, organizational structure, hierarchy, supervisory ratio and work group size. Key publications (1975–2007) and seminal works were included.Review methods.  Morse’s concept analysis approach was used to determine the pragmatic utility of the concept. A critical appraisal of the literature assessed the use of the concept across disciplines, identified inconsistencies within the concept, and uncovered assumptions and conceptual gaps.Findings.  At the organizational level, span represents supervisory capability. At the level of the manager, span may reflect reporting structure, closeness of contact, or scope of the role. At the work group level, span quantifies work group size. At the employee level, span represents employee support. These measures are influenced by units of measurement and by context.Conclusion.  A systematic understanding of span of management concepts, measures and determinants will assist nurse executives in selecting parameters to quantify the allocation of managerial resources. Researchers can incorporate these parameters in comparisons across studies and in advancing the science of nursing management.