bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bilateral adrenal incidentalomas differ from unilateral adrenal incidentalomas in subclinical cortisol hypersecretion but not in potential clinical implications
Authors: Vassilatou Evangeline , Vryonidou Andromachi , Ioannidis Dimitrios , Paschou Stavroula A , Panagou Maria , Tzavara Ioanna 
Published: April 2014

ObjectiveTo investigate the possibility of a different prevalence of subclinical Cushing's syndrome (SCS) and potentially related morbidities between patients with unilateral adrenal incidentalomas (UAI) and bilateral adrenal incidentalomas (BAI), as existing data are few and controversial.DesignProspective observational study.MethodsClinical examination, biochemical tests, and hormonal evaluation were performed in 298 consecutive patients with adrenal incidentalomas, unilateral in 224 patients (75.2%), bilateral in 74 patients (24.8%), with apparently benign masses based on imaging characteristics and after exclusion of overt endocrine disease. The diagnosis of SCS was based on a post-dexamethasone suppression test (2 mg dexamethasone/24 h for 48 h), with serum cortisol level ≥1.8 μg/dl combined with at least one abnormal result of the other hormonal measurements.ResultsSCS was diagnosed in 66 out of 298 (22.1%) patients, being more frequent in patients with BAI (35.1 vs 17.9%,P=0.003, for BAI and UAI respectively). Hypertension, type 2 diabetes mellitus, impaired glucose tolerance, and dyslipidemia were of a similar frequency in both groups. SCS patients with UAI and BAI did not differ in age, gender, BMI, waist circumference, and mass size. Factors related to SCS were the presence of BAI (OR, 3.24; 95% CI, 2.31–4.54) and mass size (OR, 2.63; 95% CI, 1.31–5.26).ConclusionBAI patients present more often with SCS when compared with UAI patients; however, morbidities potentially related to subtle cortisol hypersecretion were of a similar frequency in both groups. Further studies are needed to clarify whether this difference in hormonal activity may be related to different pathophysiologies.
Cross-sectional and longitudinal relation of IGF1 and IGF-binding protein 3 with lipid metabolism
Authors: Eggert Marie-Luise , Wallaschofski Henri , Grotevendt Anne , Nauck Matthias , Völzke Henry , Samietz Stefanie , Friedrich Nele 
Published: April 2014

BackgroundPrevious intervention studies in patients with GH disorders suggested an impact of IGF1 and IGF-binding protein 3 (IGFBP3) on lipid metabolism, whereas population-based studies revealed conflicting results. Therefore, we aimed to assess the cross-sectional and longitudinal associations between IGF1 or IGFBP3 serum levels and lipids (total, LDL, or HDL cholesterol and triglycerides) in a large-scale study.MethodsData of 2935 subjects (1356 women) from the population-based Study of Health in Pomerania (SHIP) were used. ANOVA, quantile regression, and logistic regression models adjusted for age, waist circumference, physical activity, and alcohol consumption were performed.ResultsIn cross-sectional analyses, we detected that IGF1 and IGFBP3 levels were positively related to total and LDL cholesterol and inversely related to HDL cholesterol in both sexes. Furthermore, IGFBP3 levels showed a positive relationship to triglycerides. In total, IGFBP3 levels were more strongly associated to lipids than IGF1. In longitudinal analysis, we found no influence of baseline IGF1 or IGFBP3 serum concentration on incidentally elevated or reduced lipid levels. However, the positive relationship between IGFBP3 and incidentally elevated triglycerides barely missed statistical significance in women.ConclusionThe present study showed strong cross-sectional associations between IGF1 or IGFBP3 and lipids, whereas no longitudinal relationships were revealed. Therefore, our findings suggest IGF1 and IGFBP3 as a risk marker rather than a risk factor for alterations in lipid metabolism. Further studies are needed to elucidate the mechanisms underlying the association between the GH/IGF axis and lipid metabolism.
Tissue-specific dysregulation of 11β-hydroxysteroid dehydrogenase type 1 in overweight/obese women with polycystic ovary syndrome compared with weight-matched controls
Authors: Gambineri Alessandra , Fanelli Flaminia , Tomassoni Federica , Munarini Alessandra , Pagotto Uberto , Andrew Ruth , Walker Brian R , Pasquali Renato 
Published: April 2014

ContextAbnormal cortisol metabolism in polycystic ovary syndrome (PCOS) has been invoked as a cause of secondary activation of the hypothalamic–pituitary–adrenal axis and hence androgen excess. However, this is based on urinary excretion of cortisol metabolites, which cannot detect tissue-specific changes in metabolism and may be confounded by obesity.ObjectiveTo assess cortisol clearance and whole-body and tissue-specific activities of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 (HSD11B1)) in PCOS.DesignCase–control study.SettingMedical center.PatientsA total of 20 overweight–obese unmedicated Caucasian women with PCOS, aged 18–45 years, and 20 Caucasian controls matched for age, BMI, body fat distribution, andHSD11B1genotypes (rs846910 and rs12086634).Main outcome measuresCortisol metabolites were measured in 24 h urine. During steady-state 9,11,12,12-[2H]4-cortisol infusion, cortisol clearance was calculated and whole-body HSD11B1 activity was assessed as the rate of appearance of 9,12,12-2H3-cortisol (d3-cortisol). Hepatic HSD11B1 activity was quantified as the generation of plasma cortisol following an oral dose of cortisone. Subcutaneous adipose HSD11B1 activity andHSD11B1mRNA were measured,ex vivo, in biopsies.ResultsUrinary cortisol metabolite excretion, deuterated cortisol clearance, and the rate of appearance of d3-cortisol did not differ between patients with PCOS and controls. However, hepatic HSD11B1 conversion of oral cortisone to cortisol was impaired (P<0.05), whereas subcutaneous abdominal adipose tissueHSD11B1mRNA levels and activity were increased (P<0.05) in women with PCOS when compared with controls.ConclusionsTissue-specific dysregulation of HSD11B1 is a feature of PCOS, over and above obesity, whereas increased clearance of cortisol may result from obesity rather than PCOS.
Minimally invasive versus open transforaminal lumbar interbody fusion: comparison of clinical outcomes among obese patients
Authors: Terman Samuel W. , Yee Timothy J. , Lau Darryl , Khan Adam A. , La Marca Frank , Park Paul 
Published: April 2014

ObjectMinimally invasive (MI) transforaminal lumbar interbody fusion (TLIF) has been demonstrated in previous studies to offer improvement in pain and function comparable to those provided by the open surgical approach. However, comparative studies in the obese population are scarce, and it is possible that obese patients may respond differently to these two approaches. In this study, the authors compared the clinical benefit of open and MI TLIF in obese patients.MethodsThe authors conducted a retrospective cohort study based on review of electronic medical records at a single institution. Eligible patients had a body mass index (BMI) ≥ 30 kg/m2, were ≥ 18 years of age, underwent single-level TLIF between 2007 and 2011, and outcome was assessed at a minimum 6 months postoperatively. The authors categorized patients according to surgical approach (open vs MI TLIF). Outcome measures included postoperative improvement in visual analog scale (VAS), Oswestry Disability Index (ODI), estimated blood loss (EBL), and hospital length of stay (LOS).ResultsA total 74 patients (21 open and 53 MI TLIF) were studied. Groups had similar baseline characteristics. The median BMI was 34.4 kg/m2(interquartile range 31.6–37.5 kg/m2). The mean follow-up time was 30 months (range 6.5–77 months). The mean improvement in VAS score was 2.8 (95% CI 1.9–3.8) for the open group (n = 21) and 2.4 (95% CI 1.8–3.1) for the MI group (n = 53), which did not significantly differ (unadjusted, p = 0.49; adjusted, p = 0.51). The mean improvement in ODI scores was 13 (95% CI 3–23) for the open group (n = 14) and 15 (95% CI 8–22) for the MI group (n = 45), with no significant difference according to approach (unadjusted, p = 0.82; adjusted, p = 0.68). After stratifying by BMI (< 35 kg/m2and ≥ 35 kg/m2), there was still no difference in either VAS or ODI improvement between the approaches (both unadjusted and adjusted, p > 0.05). Complications and EBL were greater for the open group than for the MI group (p < 0.05).ConclusionsObese patients experienced clinically and statistically significant improvement in both pain and function after undergoing either open or MI TLIF. Patients achieved similar clinical benefit whether they underwent an open or MI approach. However, patients in the MI group experienced significantly decreased operative blood loss and complications than their counterparts in the open group.
Low risk for subsequent subarachnoid hemorrhage for emergency department patients with headache, bloody cerebrospinal fluid, and negative findings on cerebrovascular imaging
Authors: Thomas Lisa E. , Czuczman Amanda D. , Boulanger Alyson B. , Peak David A. , Miller Emily S. , Brown David F. M. , Marill Keith A. 
Published: April 2014

Object
When patients present to the emergency department (ED) with acute headache concerning for subarachnoid hemorrhage (SAH) and a lumbar puncture (LP) shows blood in the CSF, it is difficult to distinguish the results of a traumatic LP from those of SAH. CT angiography (CTA) is often performed, but the long-term outcome for patients with a positive LP and normal neurovascular imaging remains uncertain. The primary objective of this study was to determine whether patients who presented to the ED with acute headache and had red blood cells (RBCs) in their CSF on LP but negative cerebrovascular imaging suffered subsequent SAH.

Methods
A case series study of consecutive adult ED patients who incurred charges for LP between 2001 and 2009 was performed from 2010 through 2011. Inclusion criteria were: headache, > 5 RBCs/mm3 in CSF, noncontrast head CT with no evidence of hemorrhage, and cerebrovascular CTA or MRA without aneurysm or vascular lesion within 2 weeks of the ED visit. Patients with less than 6 months of available follow-up were excluded. The primary outcomes were 1) subsequent nontraumatic SAH and 2) new vascular lesion. Secondary outcomes were complications related to SAH, or LP or angiography.

Results
Of 4641 ED patients billed for an LP, 181 patients (mean age 42 years) were included in this study. Over a median follow-up of 53 months, 0 (0%) of 181 patients (95% CI 0%–2.0%) had a subsequent SAH or new vascular lesion identified. Although not the primary outcome, there was 1 patient who was ultimately diagnosed with vasculitis. Eighteen (9.9%) of 181 patients (95% CI 6.0%–15.3%) had an LP-related complication and 0 (0%) of 181 patients (95% CI 0%–2.0%) had an angiography-related complication.

Conclusions
Patients who present to the ED with acute headache concerning for SAH and have a finding of bloody CSF on LP but negative findings on cerebrovascular imaging are at low risk for subsequent SAH and thus are likely to be safe for discharge. Replacement of the CT/LP with a CT/CTA diagnostic algorithm merits further investigation.
Revascularization and pediatric aneurysm surgery
Authors: Kalani M. Yashar S. , Elhadi Ali M. , Ramey Wyatt , Nakaji Peter , Albuquerque Felipe C. , McDougall Cameron G. , Zabramski Joseph M. , Spetzler Robert F. 
Published: April 2014

Object
Aneurysms are relatively rare in the pediatric population and tend to include a greater proportion of large and giant lesions. A subset of these large and giant aneurysms are not amenable to direct surgical clipping and require complex treatment strategies and revascularization techniques. There are limited data available on the management of these lesions in the pediatric population. This study was undertaken to evaluate the outcome of treatment of large and giant aneurysms that required microsurgical revascularization and vessel sacrifice in this population.

Methods
The authors retrospectively identified all cases in which pediatric patients (age < 18 years) with aneurysms were treated using cerebral revascularization in combination with other treatment modalities at their institution between 1989 and 2013.

Results
The authors identified 27 consecutive patients (19 male and 8 female) with 29 aneurysms. The mean age of the patients at the time of treatment was 11.5 years (median 13 years, range 1–17 years). Five patients presented with subarachnoid hemorrhage, 11 with symptoms related to mass effect, 2 with stroke, and 3 with seizures; in 6 cases, the aneurysms were incidental findings. Aneurysms were located along the internal carotid artery (n = 7), posterior cerebral artery (PCA) (n = 2), anterior cerebral artery (n = 2), middle cerebral artery (MCA) (n = 14), basilar artery (n = 2), vertebral artery (n = 1), and at the vertebrobasilar junction (n = 1). Thirteen were giant aneurysms (45%). The majority of the aneurysms were fusiform (n = 19, 66%), followed by saccular (n = 10, 34%). Three cases were previously treated using microsurgery (n = 2) or an endovascular procedure (n = 1). A total of 28 revascularization procedures were performed, including superficial temporal artery (STA) to MCA (n = 6), STA to PCA (n = 1), occipital artery to PCA (n = 1), extracranial-intracranial (EC-IC) bypass using radial artery graft (n = 3), EC-IC using a saphenous vein graft (n = 7), STA onlay (n = 3), end-to-end anastomosis (n = 1), and in situ bypasses (n = 6). Perioperative stroke occurred in 4 patients, but only one remained dependent (Glasgow Outcome Scale [GOS] score 3). At a mean clinical follow-up of 46 months (median 14 months, range 1–232 months), 26 patients had a good outcome (GOS score 4 or 5). There were no deaths. Five patients had documented occlusion of the bypass graft. The majority of aneurysms (n = 24) were obliterated at last follow-up. There was a single case of a residual aneurysm and one case of recurrence. Angiographic follow-up was unavailable in 3 cases.

Conclusions
Cerebral revascularization remains an essential tool in the treatment of complex cerebral aneurysms in children.
Des contes cambodgiens
Authors: Anthoine-Milhomme Joséphine 
Published: April 2014

Ce témoignage porte sur l’intérêt de l’usage des contes pour la clinique interculturelle. A travers différentes approches du Cambodge (recherche pour un DEA de psychologie auprès de la « jeune génération » cambodgienne installée à Paris, mise en place d’un atelier conte dans un dispensaire du XIII e arrondissement à Paris auprès de patients asiatiques, mise en place de groupes contes au Cambodge auprès de patients, thèse en Ethnologie et Anthropologie sociale sur le conte cambodgien), cet article montre l’utilité de dispositifs spécifiques dans la pratique de la clinique interculturelle.
The Epigenetic Face of Systemic Lupus Erythematosus
Authors: Ballestar Esteban , Esteller Manel , Richardson Bruce C. 
Published: April 2014

AbstractSystemic lupus erythematosus (SLE) is an archetypical systemic, autoimmune inflammatory disease characterized by the production of autoantibodies to multiple nuclear Ags. Apoptotic defects and impaired removal of apoptotic cells contribute to an overload of autoantigens that become available to initiate an autoimmune response. Besides the well-recognized genetic susceptibility to SLE, epigenetic factors are important in the onset of the disease, as even monozygotic twins are usually discordant for the disease. Changes in DNA methylation and histone modifications, the major epigenetic marks, are a hallmark in genes that undergo epigenetic deregulation in disease. In SLE, global and gene-specific DNA methylation changes have been demonstrated to occur. Moreover, histone deacetylase inhibitors reverse the skewed expression of multiple genes involved in SLE. In the present study, we discuss the implications of epigenetic alterations in the development and progression of SLE and how epigenetic drugs constitute a promising source of therapy to treat this disease.
Cutting Edge: High-Mobility Group Box 1 Preconditioning Protects against Liver Ischemia-Reperfusion Injury
Authors: Izuishi Kunihiko , Tsung Allan , Jeyabalan Geetha , Critchlow Nathan D. , Li Jianhua , Tracey Kevin J. , Demarco Richard A. , Lotze Michael T. , Fink Mitchell P. , Geller David A. , Billiar Timothy R. 
Published: April 2014

AbstractHigh mobility group box 1 (HMGB1) is a NF released extracellularly as a late mediator of lethality in sepsis and as an early mediator of inflammation following injury. Here we demonstrate that in contrast to the proinflammatory role of HMGB1, preconditioning with HMGB1 results in protection following hepatic ischemia/reperfusion (I/R). Pretreatment of mice with HMGB1 significantly decreased liver damage after I/R. The protection observed in mice pretreated with HMGB1 was associated with a higher expression of IL-1R-associated kinase-M, a negative regulator of TLR4 signaling, compared with controls. We thus explored the possibility that HMGB1 preconditioning was mediated through TLR4 activation. HMGB1 preconditioning failed to provide protection in TLR4 mutant (C3H/HeJ) mice, but successfully reduced damage in TLR4 wild-type (C3H/HeOuj) mice. Our studies demonstrate that in contrast to the role of HMGB1 as an early mediator of inflammation and organ damage in hepatic I/R, HMGB1 preconditioning can be protective.
Cutting Edge: Impaired Transitional B Cell Production and Selection in the Nonobese Diabetic Mouse
Authors: Quinn William J. , Noorchashm Negin , Crowley Jenni E. , Reed Amy J. , Noorchashm Hooman , Naji Ali , Cancro Michael P. 
Published: April 2014

AbstractDeveloping B cells undergo selection at multiple checkpoints to eliminate autoreactive clones. We analyzed B cell kinetics in the NOD mouse to establish whether these checkpoints are intact. Our results show that although bone marrow production is normal in NOD mice, transitional (TR) B cell production collapses at 3 wk of age, reflecting a lack of successful immature B cell migration to the periphery. This yields delayed establishment of the follicular pool and a lack of selection at the TR checkpoint, such that virtually all immature B cells that exit the bone marrow mature without further selection. These findings suggest that compromised TR B cell generation in NOD mice yields relaxed TR selection, affording autoreactive specificities access to mature pools.
Regulatory T Cells Control Uveoretinitis Induced by Pathogenic Th1 Cells Reacting to a Specific Retinal Neoantigen
Authors: Terrada Céline , Fisson Sylvain , De Kozak Yvonne , Kaddouri Mohammed , Lehoang Phuc , Klatzmann David , Salomon Benoît L. , Bodaghi Bahram 
Published: April 2014

AbstractIn many clinical cases, uveitis develops secondary to an infection. This could result from peripheral activation followed by ocular penetration and reactivation of T cells specific for microbial Ags expressed in the retina. To gain insights into the pathophysiology of uveitis, we developed a new mouse model based on stable retinal expression of influenza virus hemagglutinin (HA) neoantigen by adeno-associated virus-mediated gene transfer. One month thereafter, we adoptively transferred HA-specific T cells, which were activated in vitro or in vivo. Intraocular inflammation was clinically and histologically observed in all animals within 15 days. The ocular infiltrate was composed mostly of macrophages and HA-specific T cells with a proinflammatory cytokine profile. Depletion of CD4+CD25+ regulatory T cells exacerbated the disease, whereas HA-specific CD4+CD25+ T cells given i.v. controlled the disease. This novel model should allow to better study the pathophysiology and therapeutic of uveitis.
Strong TCR Signaling, TLR Ligands, and Cytokine Redundancies Ensure Robust Development of Type 1 Effector T Cells
Authors: Nembrini Chiara , Abel Brian , Kopf Manfred , Marsland Benjamin J. 
Published: April 2014

AbstractT cell effector function is a central mechanism of adaptive immunity, and accordingly, protection of the host against pathogens. One of the primary effector molecules produced by T cells in response to such pathogens is the cytokine, IFN-γ. Although the signaling pathways associated with the production of IFN-γ are well established, disparate in vivo and in vitro results indicate that distinct pathways may become more prominent dependent upon the nature of the infection, inflammatory milieu and tissue localization. We have examined the roles and requirements of the major IFN-γ-inducing pathways in vivo and in vitro, specifically: strength of TCR signal; paracrine release of IL-12, IL-23, and IL-18; and autocrine production of IFN-γ. Our data show a dynamic interaction between these activation pathways, which allows the host a degree of flexibility and redundancy in the induction of IFN-γ. Upon strong signaling through the TCR, IL-12, IL-18, and IL-23 play negligible roles in the induction of IFN-γ, whereas autocrine IFN-γ is an important component in sustaining its own secretion. However, the absence of any one of these factors during a weaker TCR signal, results in strikingly impaired T cell IFN-γ production. Of note, TLR-activated dendritic cells (DCs) were capable of overcoming the absence of a strong TCR signal, IL-12, IL-23, or IL-18 revealing an important additional mechanism for ensuring a robust IFN-γ response. Our findings clarify the hierarchical requirements of the major IFN-γ inducing pathways and highlight the important role TLR ligand-activated DCs have to preserve them.
Suppression of Complement Regulatory Proteins (CRPs) Exacerbates Experimental Autoimmune Anterior Uveitis (EAAU)
Authors: Jha Purushottam , Sohn Jeong-Hyeon , Xu Qin , Wang Yali , Kaplan Henry J. , Bora Puran S. , Bora Nalini S. 
Published: April 2014

AbstractThis study was undertaken to explore the role of complement regulatory proteins (CRPs) in experimental autoimmune anterior uveitis (EAAU). We observed that the levels of CRPs, Crry and CD59, in the eyes of Lewis rats increased during EAAU and remained elevated when the disease resolved. The in vivo role of these CRPs in EAAU was explored using neutralizing mAbs, antisense oligodeoxynucleotides (AS-ODNs), and small interfering RNAs against rat Crry and CD59. Suppression of Crry in vivo at days 9, 14, or 19 by neutralizing mAb or AS-ODNs resulted in the early onset of disease, the exacerbation of intraocular inflammation, and delayed resolution. Suppression of CD59 was only effective when the Abs and ODNs were given before the onset of disease. The most profound effect on the disease was observed when a mixture of Crry and CD59 mAbs or AS-ODNs was administered. A similar effect was observed with a combination of Crry and CD59 small interfering RNA. There was no permanent histologic damage to ocular tissue after the inflammation cleared in these animals. Increased complement activation as determined by increased deposition of C3, C3 activation fragments, and membrane attack complex was observed in the eyes of Lewis rats when the function and/or expression of Crry and CD59 was suppressed. Thus, our results suggest that various ocular tissues up-regulate the expression of Crry and CD59 to avoid self-injury during autoimmune uveitis and that these CRPs play an active role in the resolution of EAAU by down-regulating complement activation in vivo.