tbuckley/cabot-search huggingface dataset:
Pediatric Donation After Circulatory Determination of Death: Respecting the Interests of Children Through Routine Consideration of Donation Opportunities
Authors: Dominique E. Martin, Marion J. Siebelink, Beatriz Domínguez-Gil
Journal: The American Journal of Bioethics (2015)

Overby and colleagues (2015) highlight the complexities of consent to or authorization for organ procurement in the setting of controlled donation after circulatory determination of death (cDCDD). They note that decision making about cDCDD is complicated by clinical uncertainties and ethical controversies regarding protocols for the determination of death by circulatory criteria and the use of perimortem interventions to support organ procurement, and that these uncertainties and controversies may be exacerbated in the pediatric context. Suggesting that parents and clinicians may “unconsciously” compromise the best interests of their own children and patients in order to achieve organ procurement goals, Overby and colleagues argue that children are at risk of instrumentalization when the option of cDCDD is presented. This claim is further grounded in their belief that children lack autonomy and can have no interest in becoming organ donors. In this commentary, we contest these assumptions, the implications of which extend beyond cDCDD and threaten to undermine programs of pediatric deceased donation, including donation after the neurologic determination of death (DNDD). We argue that routine consideration of the possibility of organ donation by critically ill children is consistent with respect for children’s best interests and, most importantly, their human dignity.
On the course of anorexia nervosa
Authors: R. C. Casper, John M. Davis
Journal: American Journal of Psychiatry (1977)

The authors trace three phases in the course of anorexia nervosa and compare its physical and psychological symptoms with those of starvation. Phase I, which may occur months or years before the illness, usually includes precipitating events that result in loss of self-esteem and increased self-consciousness about physical appearance. During phase II patients develop the "anorectic attitude," an unreasonable fear of eating, and show pride in their ability to lose weight. By phase III patients are forced by the severity of starvation symptoms to admit that they are ill. Although many of the physical symptoms of starvation and anorexia nervosa are similar, anorectic patients, in contrast to victims of starvation, show high initiative, the ability to suppress hunger, restless hyperactivity, and body image distortion.
Blue-black rule: a simple dermoscopic clue to recognize pigmented nodular melanoma
Authors: G. Argenziano, C. Longo, A. Cameron, S. Cavicchini, J.-Y. Gourhant, A. Lallas, I. McColl, C. Rosendahl, L. Thomas, D. Tiodorovic-Zivkovic, P. Zaballos, I. Zalaudek
Journal: British Journal of Dermatology (2011)

Dermoscopy improves melanoma recognition, but most criteria were described in the context of superficial spreading melanoma.To test whether pigmented nodular melanoma could be recognized dermoscopically by the presence of a combination of blue and black colour within the lesion.Dermoscopic images of histopathologically diagnosed pigmented nodular tumours with no (or only minimal) flat component were evaluated for the presence of standard melanoma criteria and for the presence of a new feature named blue-black (BB) colour. Sensitivity, specificity, positive predictive value and negative predictive value were calculated for standard criteria and BB feature in relation to the diagnosis of melanoma and to diagnosis of malignancy.Of 283 lesions, 160 were malignant, including 78 (27·6%) melanomas, and 123 were benign. The BB feature and the standard criteria had 78·2% and 43·6% sensitivity for melanoma, respectively, whereas a combined method based on the presence of either the BB feature or one (or more) of the standard criteria reached 84·6% sensitivity, with 80·5% specificity and 93·2% negative predictive value. Sensitivity values for malignant lesions were only 24·4%, 56·9% and 60% for standard criteria, BB feature and the combined method, respectively. However, the combined method gave 91·9% specificity and 90·6% positive predictive value for malignancy.Using a method based on the BB feature or one of the standard melanoma criteria, only 9·4% of positive pigmented nodular lesions were found to be benign and only 6·8% of negative lesions were found to be melanoma histopathologically.
Nrf2, but not β‐catenin, mutation represents an early event in rat hepatocarcinogenesis
Authors: Patrizia Zavattari, Andrea Perra, Silvia Menegon, Marta Anna Kowalik, Annalisa Petrelli, Maria Maddalena Angioni, Antonia Follenzi, Luca Quagliata, Giovanna Maria Ledda‐Columbano, Luigi Terracciano, Silvia Giordano, Amedeo Columbano
Journal: Hepatology (2015)

Hepatocellular carcinoma (HCC) develops through a multistage process, but the nature of the molecular changes associated with the different steps, the very early ones in particular, is largely unknown. Recently, dysregulation of the NRF2/KEAP1 pathway and mutations of these genes have been observed in experimental and human tumors, suggesting their possible role in cancer development. To assess whether Nrf2/Keap1 mutations are early or late events in HCC development, we investigated their frequency in the rat Resistant Hepatocyte model, consisting of the administration of diethylnitrosamine followed by a brief exposure to 2‐acetylaminofluorene. This model enables the dissection of all stages of hepatocarcinogenesis. We found that Nrf2/Keap1 mutations were present in 71% of early preneoplastic lesions and in 78.6% and 59.3% of early and advanced HCCs, respectively. Mutations of Nrf2 were more frequent, missense, and located in the Nrf2‐Keap1 binding region. Mutations of Keap1 occurred at a much lower frequency in both preneoplastic lesions and HCCs and were mutually exclusive with those of Nrf2 . Functional in vitro and in vivo studies showed that Nrf2 silencing inhibited the ability of tumorigenic rat cells to grow in soft agar and to form tumors. Unlike Nrf2 mutations, those of Ctnnb1 , which are frequent in human HCC, were a later event as they appeared only in fully advanced HCCs (18.5%). Conclusion : In the Resistant Hepatocyte model of hepatocarcinogenesis the onset of Nrf2 mutations is a very early event, likely essential for the clonal expansion of preneoplastic hepatocytes to HCC, while Ctnnb1 mutations occur only at very late stages. Moreover, functional experiments demonstrate that Nrf2 is an oncogene critical for HCC progression and development. (H epatology 2015;62:851‐862)
Overseas members of the BMA: Forgotten members should be recognised.
Authors: Peter A Sims
Journal: BMJ (2003)

Editor—I resonated with Kisely's letter on the forgotten overseas members of the BMA.1 After years within the vineyard of the NHS my first instinct is relief not to be part of BMA politics, GMC utterances, and royal college solemnities. They can be more comfortably observed from here.

However, we are now doctors in a global village and should encourage health workers to be internationalists. There should be an internationally recognised and accredited medical qualification. The citizens of the world should reasonably expect common standards and expertise from the medical profession. In the same way, the continued validation of skills and registration must work towards an international perspective.

The BMA is a British phenomenon, but the BMJ is an international publication. Plainly, overseas members should be listened to, and in the age of electronic communication this is not difficult. International committees should be international. The same arguments apply to the royal colleges, which are often strikingly parochial.

In a working lifetime I have worked three times overseas and twice returned to work in Britain. This is not unique. Such medical nomads may be difficult people with their different exposures, perspectives, and experience, but they are important and could make important contribution.
Safety, molecular, and imaging responses to cetuximab administered in a window pre-operative study in squamous cell carcinoma of the head and neck (SCCHN).
Authors: Sandra Schmitz, Marc Hamoir, Herve Reychler, Michele Magremanne, Birgit Weynand, Renaud Lhommel, Francois-Xavier Hanin, Max Lonneux, Denis Rommel, Nicolas Michoux, Thierry Duprez, Jean-Pascal H. Machiels
Journal: Journal of Clinical Oncology (2012)

5519 Background: Only a minority of SCCHN pts benefits from anti-EGFR mAbs. Trials with pre- and post-therapy tumor biopsies are crucial to better characterize the molecular pathways involved in treatment response or resistance. Targeted agents (TA) are often investigated in unselected end-stage cancer pts, making difficult optimal translational research. One way to resolve this issue is to perform “window” studies where a TA is given during the incompressible period between the diagnosis and surgery. Methods: We conducted a phase I/II study: cetuximab (C) was given pre-operatively to treatment-naïve SCCHN pts selected for primary curative surgery. C (400mg/m2 first wk followed by 250mg/m2/wk) was given during 2 wks (day -15 until day -1, 3 infusions) before surgery (day 0). Tumour biopsies, FDG/PET, and CT were performed at diagnosis and surgery. In the phase I, we investigated the safety of preoperative C by progressively reducing the delay between the last dose of C and surgery (minimum delay : 24 hrs ; 3+3 phase 1 design). The aims of the phase II were (i) safety, (ii) C activity by FDG-PET (P o =0.10, P 1 =0.35, a=0.05 and b= 0.10). As controls, 5 additional pts were included without C treatment but with the same requirements regarding biopsies and imaging. Results: The phase 1 study (n=18) demonstrated that C infusion given 24 hrs before surgery was safe. Safety was confirmed in the phase II (n=20). 90 % had a FDG-PET partial response (PR) (EORTC guideline) in the C group and 0% in the controls. 52% had a ΔSUVmax decrease of &gt;50%. 2 pts evaluable by CT/MRI had a PR (RECIST). Then, we compared the pre-and post treatment biopsies by immunochemistry. For the whole group, C did not reduce Ki67 (p=0.1) and did not seem to induce apoptosis (caspase). However, for pts with ΔSUVmax decrease &gt; 25% or &gt; 50%, Ki67 was decreased (p=0.04 and 0.006). C induced downregulation of pEGFR (p=0.0004) and pERK (p=0.007) but not pAKT/AKT (Histoscore). Conclusions: Pre-operative study with C is safe. Our findings suggest that the main downstream molecular pathway blocked by C in SCCHN is the RAS/RAF/ERK. Further analyses are ongoing to better characterize molecular response and escape mechanisms.
Treatment of severe obsessive-compulsive disorder with fluvoxamine
Authors: L H Price, W K Goodman, D S Charney, S A Rasmussen, G R Heninger
Journal: American Journal of Psychiatry (1987)

Ten obsessive-compulsive patients received single-blind treatment with fluvoxamine, a selective serotonin reuptake inhibitor, for several weeks following at least 2 weeks of placebo. The group showed significant improvement, as measured by several clinical scales and self-ratings; six patients were judged responders. Fluvoxamine appears effective in treating severe obsessive-compulsive disorder.
The agreement between inhaled mannitol airway challenge and exercise challenge in young children
Authors: Afaf Alblooshi, Shannon Simpson, Georgia Banton, Stephen Stick, Graham Hall
Journal: European Respiratory Journal (2013)

Background: Inhaled mannitol and exercise challenge tests are used to assess exercise induced broncho-constriction in adults and school aged children. The forced oscillation technique (FOT) enables lung function and inhaled airway challenge tests in young children. There are limited reports of exercise challenge tests and no reports of mannitol challenge tests in young children with a history of exercise induced respiratory symptoms (EIS).  Aims: To assess the agreement between mannitol and exercise challenge tests in young children using FOT.  Methods: Healthy children and children with EIS were recruited. Children underwent a mannitol challenge and free running exercise challenge on 2 different visits 1-2 weeks apart. A positive responsiveness to the challenge tests was defined as wheeze on auscultation, persistent cough, SpO2 below 90% or increase in the respiratory resistance at 8 Hz (Rrs8) >50% from control inhalations.  Results: To date 37 children with a mean (range) age of 6 (4–7) years were enrolled of which 28 children performed both challenge tests. None of the healthy children (n=8) responded to either challenges. Of the 20 children with EIS 13 (65%) responded to the mannitol challenge with 8 children (40%) responding to the exercise challenge. In the children with EIS 7 children responded to both challenges and 6 children did not respond to either challenge resulting concordant outcomes in 13 children (65%) with EIS and in 100% of healthy children.  Conclusion: These data suggest a mannitol challenge test combined with FOT may aid in the diagnosis of exercise induced asthma in young children and may offer an alternative to an exercise challenge test.
Does bone structure accurately reflect serum FGF23 levels in patients with chronic kidney disease?
Authors: Keitaro Yokoyama, Akio Nakashima, Yukio Maruyama, Ichiro Ohkido, Takashi Yokoo
Journal: Kidney International (2015)

Serum fibroblast growth factor 23 (FGF23) levels regulate serum phosphate levels and are thought to be related to systemic complications, including in the cardiovascular system,1.Faul C. Amaral A.P. Oskouei B. et al.FGF23 induces left ventricular hypertrophy.J Clin Invest. 2011; 121: 4393-4408Crossref PubMed Scopus (1468) Google Scholar in patients with chronic kidney disease (CKD). Patients with autosomal dominant hypophosphatemic rickets (ADHR) develop hypophosphatemia because these patients harbor a mutation in FGF23 making it resistant to degradation. However, a high incidence of cardiovascular complications has not been reported in ADHR patients. Interestingly, serum levels of intact, biologically active FGF23 in patients with ADHR do not significantly differ from that in healthy controls.2.Imel E.A. Peacock M. Gray A.K. et al.Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans.J Clin Endocrinol Metab. 2011; 96: 3541-3549Crossref PubMed Scopus (205) Google Scholar Changes in bone structure in ADHR patients are caused by a slight increase in FGF23 levels, which may indicate that serum FGF23 levels are not always related to the effects of FGF23 on bone.2.Imel E.A. Peacock M. Gray A.K. et al.Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans.J Clin Endocrinol Metab. 2011; 96: 3541-3549Crossref PubMed Scopus (205) Google Scholar Therefore, we should consider the relationship between serum FGF23 levels and bone structure. Our point is that significant changes occur in serum FGF23 levels in patients with CKD who often develop Osteitis fibrosa yet bone turnover may have an influence on FGF23 secretion. In the paper by Pereira et al.,3.Pereira R.C. Delany A.M. Khouzam N.M. et al.Primary osteoblast-like cells from patients with end-stage kidney disease reflect gene expression, proliferation, and mineralization characteristics ex vivo.Kidney Int. 2015; 87: 593-601Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar human bone cells cultured from adult patients with CKD were shown to be an ex vivo model to reflect gene expression in osteoblasts and osteocytes. This model may be appropriate to evaluate the pathophysiologic relation between bone lesions and serum FGF23 in patients with CKD. We suggest that it is necessary to consider bone structural changes in Osteitis fibrosa when evaluating FGF23 metabolism.4.Ohkido I. Yokoyama K. Kagami S. et al.The hypothesis that bone turnover influences FGF23 secretion.Kidney Int. 2010; 77: 743-744Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar
Global and regional lung function in a population of healthy children before and after exercise challenge
Authors: Barbara Vogt, Sarah Löhr, Zhanqi Zhao, Christian Falkenberg, Norbert Weiler, Inéz Frerichs
Journal: European Respiratory Journal (2014)

Introduction: Electrical impedance tomography (EIT) is able to determine the spatial distribution of lung ventilation. The aim of our study was to assess the global (by spirometry) and regional lung function (by EIT) in a population of healthy children living on the North Sea island Amrum before and after exercise challenge.  Patients and methods: We examined 3 groups of healthy children with no history of lung disease: A) 31 children aged 6-9 yr, B) 39 aged 10-13 yr, C) 21 aged 14-16 yr using EIT in parallel with spirometry at baseline and after stairs running for 5 min. EIT data were collected at 33 scans/s. We determined the regional EIT-derived parameters: FEV 1 , FVC, FEV 1 /FVC and FEF 75  in 912 image pixels before and 5 min after exercise. Spatial heterogeneity of ventilation was characterized by the coefficient of variation (CV) calculated from all pixel values of these parameters.  Results: The global lung function parameters determined by spirometry at baseline did not significantly differ from the GLI reference values: mean z-scores for FEV 1 , FVC, FEV 1 /FVC, FEF 75  were -0.39, -0.59, 0.52, 0.34 (group A); -0.40, -0.17, 0.47, -0.13 (group B); -0.39, 0.13, -0.83, -0.28 (group C). Significant exercise-dependent changes were only found in FVC, FEV 1 /FVC and FEF 75  in the youngest children (group A). CV of regional FEV 1 , FVC, FEV 1 /FVC and FEF 75  showed no significant differences within the groups before and after exercise.  Conclusion: Healthy children aged 6-9 yr were susceptible to exercise challenge at the global lung level as detected by conventional pulmonary function testing. The spatial ventilation distribution determined by EIT was unaffected by exercise independent of age.
Airflow limitation is associated with reduced skeletal muscle mass in community-dwelling older men
Authors: Naoto Fukutani, Minoru Yamada, Daiki Adachi, Tomoki Aoyama, Tadao Tsuboyama
Journal: European Respiratory Journal (2014)

Introduction:  Muscle wasting is a severe problem in patients with chronic obstructive pulmonary disease. Recent reports suggest that airflow limitation (AL) is present in community-dwelling older adults.   Aim:  To analyze the relation between AL and the skeletal muscle mass index (SMI) in Japanese community-dwelling older men by performing a cross-sectional study.   Methods:  The study included 121 men aged ≥65 years. The age, body mass index (BMI), smoking history, medical history, pulmonary function, motor function, SMI, and physical activity (PA) of each participant were obtained. AL was defined as FEV 1 /FVC%   Results:  AL was present in 29 (24.0%) participants. While age, smoking history, and motor function were not significantly different between the groups, BMI ( P   2 ; without AL: 7.5 ± 0.7 kg/m 2 ;  P   P   P  = 0.001; 95% CI: -0.874, -0.219) was significantly associated with a reduced SMI.   Conclusions:  Our data showed that AL is associated with a reduced SMI in community-dwelling older men.
The ring vaccination trial: a novel cluster randomised controlled trial design to evaluate vaccine efficacy and effectiveness during outbreaks, with special reference to Ebola
Journal: BMJ (2015)

A World Health Organization expert meeting on Ebola vaccines proposed urgent safety and efficacy studies in response to the outbreak in West Africa. One approach to communicable disease control is ring vaccination of individuals at high risk of infection due to their social or geographical connection to a known case. This paper describes the protocol for a novel cluster randomised controlled trial design which uses ring vaccination. In the Ebola ça suffit ring vaccination trial, rings are randomised 1:1 to (<i>a</i>) immediate vaccination of eligible adults with single dose vaccination or (<i>b</i>) vaccination delayed by 21 days. Vaccine efficacy against disease is assessed in participants over equivalent periods from the day of randomisation. Secondary objectives include vaccine effectiveness at the level of the ring, and incidence of serious adverse events. Ring vaccination trials are adaptive, can be run until disease elimination, allow interim analysis, and can go dormant during inter-epidemic periods.
Abstract 17973: KLF6 Modulates Aortic Aneurysm Formation by Balancing Between Inflammatory and TGFβ Signaling Pathways
Authors: Bo K Son, Toru Suzuki, Daigo Sawaki, Kenichi Aizawa, Hong Zhan, Junichi Ishida, Takayoshi Matsumura, Ryozo Nagai
Journal: Circulation (2012)

[Background] The transcription factor, Kruppel-like factor 6 (KLF6) has been shown to play important roles in the regulation of diverse cellular processes through TGFβ signaling. Recently, TGFβ si...
Cystoscopy. A Theoretical and Practical Handbook containing Chapters on Separate Renal Function and Pyelography.
Authors: Jas. B. MacAlpine
Journal: JAMA (1927)

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Second-Generation BCR-ABL Kinase Inhibitors in CML
Authors: Bengt Simonsson, Kimmo Porkka, Johan Richter
Journal: New England Journal of Medicine (2010)

To the Editor: For patients with newly diagnosed chronic myeloid leukemia (CML) in the chronic phase, a complete cytogenetic response at 12 months is widely accepted as an optimal response.1 This response was used as a primary end point in the trial of dasatinib versus imatinib by Kantarjian et al. (June 17 issue).2 Although a major molecular response at 18 months is also considered an optimal response,1 Saglio et al.,3 in the same issue of the Journal, reduced the time to 12 months. We would be grateful if the authors could explain whether a major molecular response at 12 months is a valid surrogate in trials of first-line treatments for CML in the chronic phase and how we should evaluate the treatment response when a patient does not reach this goal in daily clinical practice.
The Anti-Sickling Agent Aes-103 Decreases Sickle Erythrocyte Fragility, Hypoxia-Induced Sickling and Hemolysis In Vitro
Authors: Laurel G. Mendelsohn, Leah Pedoeim, Yekai Kevin Wang, Rehan Saiyed, Christine A. Brantner, Mathew P. Daniels, James S. Nichols, Xunde Wang, Eduard J. van Beers, Gregory J. Kato
Journal: Blood (2013)