tbuckley/cabot-search huggingface dataset:
Inhaled corticosteroids reduce growth. Or do they?
Authors: P.L.P. Brand
Journal: European Respiratory Journal (2001)

The class label warning in the United States for inhaled corticosteroids (ICS's) states that these drugs may reduce growth velocity in children. In this paper, the evidence for this warning is reviewed from a clinical point of view. Children with asthma tend to grow slower than their healthy peers during the prepubertal years because they go into puberty at a later age. However, asthmatic children do achieve a (near) normal adult height. In randomized controlled clinical trials, the use of inhaled beclomethasone, budesonide and fluticasone is associated with a reduced growth during the first months of therapy, in the order of magnitude of approximately 0.5–1.5 cm·yr −1 . It is, however, unlikely that such an effect continues or persists because accumulating evidence shows that asthmatic children, even when they have been treated with ICS for years, attain normal adult height. Individual rare cases have been reported, however, where ICS use was associated with clinically relevant growth suppression. Inhaled corticosteroids are the most effective therapy available for maintenance treatment of childhood asthma. Fear of reduced growth velocity is based on exceptional cases and not on group data. It should, therefore, not be a reason to withhold or withdraw such highly effective treatment in children with asthma.
A novel 105 basepair deletion causing ?0-thalassemia in members of a Thai family
Authors: Chamnong Nopparatana, Vannarat Saechan, Chawadee Nopparatana, Malida Pornpatkul, Vicharn Panich, Yasuyuki Fukumaki
Journal: American Journal of Hematology (1999)

We identified and characterized a novel beta(0)-thalassemia mutation due to partial deletion of the 5' end beta-globin gene including the mRNA cap site and a part of exon 1. The deletion was precisely 105 basepair (bp) in length extending from position -24 or -25 to +80 or +81 relative to the beta-globin gene mRNA cap site. This mutation was detected in three individuals from a family originating in the area of southern Thailand. The propositus was a 39-year-old female and noted to be heterozygous for beta-thalassemia with hemoglobin (Hb) level of 10.1 g/dl, MCV 70 fl, MCH 23.1 pg, HbA2 6.3%, and HbF 2.4%. Her son was 9 years of age and was also heterozygous for the mutation, having Hb level of 10.8 g/dl, MCV 58 fl, MCH 19.0 pg, HbA2 5.6%, and HbF 4.3%. Her 6-year-old daughter was affected, having a genotype of this mutation and a G-C transition at IVS 1 nt 5. Although the deletion does not include the beta-globin gene promoter sequences, the individuals heterozygous for this mutation have an elevated HbA2 level slightly higher than observed in most carriers of beta-thalassemia caused by point mutations.
Multi-Institutional Phase II Study of Selumetinib in Patients With Metastatic Biliary Cancers
Authors: Tanios Bekaii-Saab, Mitch A. Phelps, Xiaobai Li, Motoyasu Saji, Laura Goff, John Sae Wook Kauh, Bert H. O'Neil, Stephanie Balsom, Catherine Balint, Ryan Liersemann, Vasily V. Vasko, Mark Bloomston, William Marsh, L. Austin Doyle, Gilian Ellison, Michael Grever, Matthew D. Ringel, Miguel A. Villalona-Calero
Journal: Journal of Clinical Oncology (2011)

Biliary cancers (BCs) carry a poor prognosis, but targeting the RAS/RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-related kinase (ERK) pathway is of significance. Selumetinib is an inhibitor of MEK1/2, so this trial was designed to determine the safety and efficacy of selumetinib in BC.
Effects of an automated stride assistance system on walking parameters and muscular glucose metabolism in elderly adults
Authors: H Shimada, T Suzuki, Y Kimura, T Hirata, M Sugiura, Y Endo, K Yasuhara, K Shimada, K Kikuchi, K Oda, K Ishii, K Ishiwata
Journal: British Journal of Sports Medicine (2008)

To identify the effects of an automated stride assistance system (SAS) on walking scores and muscle activities in the lower extremities of elderly people.Seven healthy elderly men (73-81 years) participated in this study. Subjects walked continuously at a constant speed for 50 min on a treadmill with and without the SAS, which is a device to control the walk ratio (step length/cadence) and to add support power to the thigh during walking. A step counter equipped with an infrared device was used to record walking data. The average speeds during treadmill walking were 2.89-3.82 km/h without the SAS and 3.03-4.03 km/h with the SAS. Positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG) evaluation of glucose metabolism were conducted on each subject twice after walking with and without the SAS.Walk ratio, walking speed and step length were significantly improved in all subjects by the SAS, while cadence was significantly decreased by the SAS in all subjects except one. The SAS did not have a significant effect on glucose metabolism of the muscles of the lower extremities. There were no significant correlations between change in walking speed and change in glucose metabolism in each muscle without the SAS and with the SAS. In contrast, significant correlations between walking speed and glucose metabolism were shown in gluteus minimus (r = -0.929), hip-related muscles (r = -0.862), soleus (r = -0.907), and medial gastrocnemius (r = -0.952) without the SAS. With the SAS, there were significant correlations in gluteus medius (r = -0.899), hip-related muscles (r = -0.819), and medial gastrocnemius (r = -0.817) in the elderly subjects.The SAS increases walking scores in elderly people without increasing energy consumption of lower-extremity muscles. The elderly subjects with low walking speed showed higher glucose metabolism in hip-related muscles and triceps surae. Thus, this association suggested that decreased walking speed in elderly adults has a higher metabolic cost in these muscle regions.
Anatomical Alterations of the Visual Motion Processing Network in Migraine with and without Aura
Authors: Cristina Granziera, Alexandre F. M DaSilva, Josh Snyder, David S Tuch, Nouchine Hadjikhani
Journal: PLoS Medicine (2006)

Background Patients suffering from migraine with aura (MWA) and migraine without aura (MWoA) show abnormalities in visual motion perception during and between attacks. Whether this represents the consequences of structural changes in motion-processing networks in migraineurs is unknown. Moreover, the diagnosis of migraine relies on patient's history, and finding differences in the brain of migraineurs might help to contribute to basic research aimed at better understanding the pathophysiology of migraine. Methods and Findings To investigate a common potential anatomical basis for these disturbances, we used high-resolution cortical thickness measurement and diffusion tensor imaging (DTI) to examine the motion-processing network in 24 migraine patients (12 with MWA and 12 MWoA) and 15 age-matched healthy controls (HCs). We found increased cortical thickness of motion-processing visual areas MT+ and V3A in migraineurs compared to HCs. Cortical thickness increases were accompanied by abnormalities of the subjacent white matter. In addition, DTI revealed that migraineurs have alterations in superior colliculus and the lateral geniculate nucleus, which are also involved in visual processing. Conclusions A structural abnormality in the network of motion-processing areas could account for, or be the result of, the cortical hyperexcitability observed in migraineurs. The finding in patients with both MWA and MWoA of thickness abnormalities in area V3A, previously described as a source in spreading changes involved in visual aura, raises the question as to whether a "silent" cortical spreading depression develops as well in MWoA. In addition, these experimental data may provide clinicians and researchers with a noninvasively acquirable migraine biomarker.
Sustainability of Effects of an Early Childhood Obesity Prevention Trial Over Time
Authors: Li Ming Wen, Louise A. Baur, Judy M. Simpson, Huilan Xu, Alison J. Hayes, Louise L. Hardy, Mandy Williams, Chris Rissel
Journal: JAMA Pediatrics (2015)

<h3>Importance</h3> Little evidence exists on whether effects of an early obesity intervention are sustainable. <h3>Objective</h3> To assess the sustainability of effects of a home-based early intervention on children's body mass index (BMI) and BMI<i>z</i>score at 3 years after intervention. <h3>Design, Setting, and Participants</h3> A longitudinal follow-up study of the randomized clinical Healthy Beginnings Trial was conducted with 465 participating mothers consenting to be followed up at 3 years after intervention until their children were age 5 years. This study was conducted in socially and economically disadvantaged areas of Sydney, Australia, from March 2011 to June 2014. <h3>Interventions</h3> No further intervention was carried out in this Healthy Beginnings Trial phase 2 follow-up study. The original intervention in phase 1 comprised 8 home visits from community nurses delivering a staged home-based intervention, with one visit in the antenatal period and 7 visits at 1, 3, 5, 9, 12, 18, and 24 months after birth. <h3>Main Outcomes and Measures</h3> Primary outcomes were children's BMI and BMI<i>z</i>score. Secondary outcomes included dietary behaviors, quality of life, physical activity, and TV viewing time of children and their mothers. <h3>Results</h3> In total, 369 mothers and their children completed the follow-up study, a phase 2 completion rate of 79.4% (80.9% for the intervention group and 77.7% for the control group). The differences between the intervention and control groups at age 2 years in children's BMI and BMI<i>z</i>score disappeared over time. At age 2 years, the difference (intervention minus control) in BMI (calculated as weight in kilograms divided by height in meters squared) was −0.41 (95% CI, −0.71 to −0.10;<i>P</i> = .009), but by age 5 years it was 0.03 (95% CI, −0.30 to 0.37). No effects of the early intervention on dietary behaviors, quality of life, physical activity, and TV viewing time were detected at age 5 years. <h3>Conclusions and Relevance</h3> The significant effect of this early life home-visiting intervention on child BMI and BMI<i>z</i>score at age 2 years was not sustained at age 5 years without further intervention. Obesity prevention programs need to be continued or maintained during the early childhood years.
STAT3 activation via interleukin 6 trans-signalling contributes to ileitis in SAMP1/Yit mice
Authors: K Mitsuyama
Journal: Gut (2006)

SAMP1/Yit mice spontaneously develops intestinal inflammation. Previously, we demonstrated that the signal transducer and activator of transcription (STAT)-3/suppressor of cytokine signalling (SOCS)-3 pathway is pivotal in human inflammatory bowel disease. In our studies in SAMP1/Yit mice, the aim was to investigate whether STAT3 activation contributes to ileitis and to examine the therapeutic effects of this signal blockade.Intestinal expression of phospho-STAT3 in SAMP1/Yit mice and control AKR/J mice was examined by western blotting and immunohistochemistry. SOCS3 and interleukin 6 (IL-6) mRNA were determined by northern blotting and reverse transcription-polymerase chain reaction, respectively. We also examined the effects of intravenously injected hyper-IL-6, an IL-6/soluble IL-6 receptor fusion protein, and of soluble gp130-Fc, a specific inhibitor of soluble IL-6 receptor signalling, on STAT3 phosphorylation and disease severity in SAMP1/Yit mice.Phospho-STAT3 was expressed strongly during the disease course in SAMP1/Yit mice but only transiently in AKR/J mice. Phospho-STAT3 was localised to epithelial and mononuclear cells in the diseased intestine of SAMP1/Yit mice. SOCS3 as well as IL-6 mRNAs were expressed in affected intestine. Administration of hyper-IL-6 caused disease exacerbation and enhancement of STAT3 phosphorylation. In contrast, soluble gp130-Fc administration ameliorated the disease and suppressed STAT3 phosphorylation.STAT3 signalling is critical in the development of intestinal inflammation in SAMP1/Yit mice. Blockade of this signalling pathway by soluble gp130-Fc may have therapeutic effects in inflammatory bowel disease.
Dietary Sodium Intake Regulates the Ubiquitin-Protein Ligase Nedd4-2 in the Renal Collecting System
Authors: Dominique Loffing-Cueni, Sandra Y. Flores, Daniel Sauter, Dorothée Daidié, Nicole Siegrist, Pierre Meneton, Olivier Staub, Johannes Loffing
Journal: Journal of the American Society of Nephrology (2006)

The activity of the epithelial sodium (Na+) channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN) needs to be tightly regulated to match urinary Na+ excretion with dietary Na+ intake. The ubiquitin-protein ligase Nedd4-2, which in vitro interacts with ENaC subunits and reduces ENaC cell surface abundance and activity by ubiquitylation of the channel, may participate in the control of ENaC. This study confirms in vivo by reverse–transcriptase–PCR that Nedd4-2 is expressed throughout the nephron and is detectable by immunoblotting in kidney extracts. By immunohistochemistry, Nedd4-2 was found to be strongly expressed in the ASDN, with low staining intensity in the late distal convoluted tubule and early connecting tubule (where apical ENaC is high) and gradually increasing detection levels toward the collecting duct (CD; where apical ENaC is low). Compared with high-Na+ diet (5% Na+), 2 wk of low-Na+ diet (0.01% Na+) drastically reduces Nedd4-2 immunostaining and increases apical ENaC abundance in ASDN. Reduced Nedd4-2 immunostaining is not dependent on increased apical Na+ entry in the CD, because it is similarly observed in mice with intact and with suppressed apical ENaC activity in the CD. Consistent with a role of mineralocorticoid hormones in the long-term regulation of Nedd4-2, 5-d treatment of cultured CD (mpkCCDcl4) cells with 1 μM aldosterone leads to reduction of Nedd4-2 protein expression. It is concluded that Nedd4-2 abundance is regulated by Na+ diet, by a mechanism that likely involves aldosterone. This regulation may contribute to adaptation of apical ENaC activity to altered Na+ intake.
Alendronate versus Calcitriol for the Prevention of Bone Loss after Cardiac Transplantation
Authors: Elizabeth Shane, Vicki Addesso, Pearila B. Namerow, Donald J. McMahon, Shaw-Hwa Lo, Ronald B. Staron, Mark Zucker, Susan Pardi, Simon Maybaum, Donna Mancini
Journal: New England Journal of Medicine (2004)

Osteoporosis is a well-known complication of cardiac transplantation. We conducted a randomized trial comparing alendronate with calcitriol for the prevention of bone loss during the first year after cardiac transplantation.A total of 149 patients were randomly assigned to receive either alendronate (10 mg per day) or calcitriol (0.5 microg per day) a mean (+/-SD) of 21+/-11 days after transplantation. Estimates of bone loss and the incidence of fractures among untreated patients were obtained from a reference group of 27 prospectively recruited patients who received cardiac transplants within the same period as the intervention groups.At one year, the bone mineral density at the lumbar spine had decreased by a mean of 0.7 percent in the alendronate group and 1.6 percent in the calcitriol group (P=0.25 for the test of no difference). The bone mineral density at the femoral neck decreased by a mean of 1.7 percent in the alendronate group and 2.1 percent in the calcitriol group (P=0.69). In the reference group, the mean bone mineral density at the lumbar spine decreased by 3.2 percent (P=0.03 for the comparison with the alendronate group; P=0.15 for the comparison with the calcitriol group), and the mean density at the femoral neck decreased by 6.2 percent (P=0.001 for comparisons with both intervention groups). The incidence of vertebral fractures did not differ significantly among the groups (6.8 percent in the alendronate group, 3.6 percent in the calcitriol group, and 13.6 percent in the reference group). Hypercalciuria developed in 27 percent of the patients in the calcitriol group and 7 percent of those in the alendronate group (P=0.01).The degree of bone loss and the rates of fracture did not differ significantly between the intervention groups. Calcitriol was associated with a higher risk of hypercalciuria. Alendronate-treated patients sustained less bone loss at the spine than those in the reference group, and both intervention groups sustained less bone loss at the hip than the reference group. The requirement for monitoring the serum and urinary calcium levels in calcitriol-treated patients makes alendronate more attractive for the prevention of bone loss early after cardiac transplantation.
A patient with back pain and fever
Authors: BJ Kingma, W van den Berg, MM Schuurmans, AH Molenaar
Journal: European Respiratory Journal (1992)

In October 1989, a 28 yr old man attended the Clinic for Internal Medicine.He complained of back pain and general malaise.In 1986, he had fled from Bangladesh to Holland.The patient had a completely blank medical history and used no medication, alcohol or drugs of any type.He smoked five cigarettes per day.The patient complained essentially of: bodily positional-dependent pain in the back, starting some 11 months previously.For the last two months, he had had a temperature of 38.5°C with occasional chills and night sweating, a slightly reduced appetite and a weight loss of 10 kg in three months.There was no alcohol-induced pain or pruritus.There were no pulmonary symptoms.On examination, we saw a slightly sick young man with a temperature of 38.4°C.Blood pressure was 130/70 mmHg; pulse rate 88 beats•min• 1 ; the neck veins were not engorged.On both sides of the neck
How<i>BJSM</i>embraces the power of social media to disseminate research
Authors: Evert Verhagen, Claire Bower, Karim M Khan
Journal: British Journal of Sports Medicine (2013)

Ways of communication have changed considerably in recent years. The latest innovation is what has become known as ‘social media’. Wikipedia (itself a social platform) defines social media as “the means of interactions among people in which they create, share and exchange information and ideas in virtual communities and networks.”1 You probably use some different social websites, for example, Twitter, Facebook, LinkedIn, ResearchGate, YouTube, Skype, Flickr, Wordpress, Reddit, Mendeley, etc. These are the more popular among a much larger mix of social platforms.

The foremost strength of social media is the constant availability of interaction with your peers through mobile devices. Today, smart phones pack the computing power of a low-end laptop in the palm of your hand. Thereby, you can communicate and share messages, pictures, videos and music, with your social network wherever you are and whenever you want.

You do not need to be an active user of social media to grasp its potential. You can be a so-called listener or lurker. “In most online communities, 90% of users are lurkers who never contribute, 9% of users contribute a little and 1% of users account for almost all the action.”2 The practical use of sifting through discussions and other people's messages is that you can follow topics of interest (eg, concussion), colleagues (eg, @RoaldBahr, @ProfJillCook) or journals, thereby gaining a very quick view of the …
<scp>l</scp> -Arginine–Induced Conducted Signals Alter Upstream Arteriolar Responsivity to <scp>l</scp> -Arginine
Authors: Mary D.S. Frame, Ingrid H. Sarelius
Journal: Circulation Research (1995)

Abstract Our purpose was to determine whether l -arginine was involved in vascular communication between downstream and upstream locations within a defined microvascular region. Arteriolar diameter was measured for the branches along a transverse arteriole in the superfused cremaster of anesthetized (pentobarbital sodium, 70 mg/kg IP) hamsters (N=53). The upstream branch arterioles dilated significantly to locally applied l -arginine (100 μmol/L pipette concentration) only if the downstream branches (≈1400 μm away) were preexposed. With exposure order downstream to upstream, diameter change was last branch, −3.8±1.5% (of baseline); third, +58.1±27%; first, +92±26% (n=5); with exposure order upstream to downstream: first branch, −0.4±3%; third, +5±11%; last, −5.6±7.5% (n=4). Thus, downstream preexposure to l -arginine altered the responsivity upstream to locally applied l -arginine. Downstream-applied l -arginine also induced a conducted vasodilation (+17.8±2.8%; n=14) 1327±166 μm upstream. This response was completely blocked by simultaneous sucrose (600 mOsm), halothane (0.0345%), or N ω -nitro- l -arginine (L-NNA, 100 μmol/L) exposure to the feed vessel (second micropipette) midway between the downstream site of l -arginine exposure and the upstream observation site. An acetylcholine-induced conducted vasodilation (+18.1±2.6%, n=8) was also completely blocked by sucrose, halothane, or L-NNA. The change in responsivity upstream to locally applied l -arginine was not seen in the absence of a conducted vasodilation or when the conducted signal pathway was blocked after the conducted vasodilation was observed, and it could be triggered by a conducted response to acetylcholine as well as to l -arginine. Thus, the change in local responsivity upstream requires an ongoing conducted signal from downstream. Conducted signals likely play a dynamic role in the regulation of vascular responsivity within a defined microvascular region.
MALIGNANT ANGIOENDOTHELIOMA OF THE SKIN
Authors: E. WILSON JONES
Journal: British Journal of Dermatology (1964)

Journal Article MALIGNANT ANGIOENDOTHELIOMA OF THE SKIN Get access E. WILSON JONES, M.R.C.P. E. WILSON JONES, M.R.C.P. Institute of Dermatology, 5, Lisle Street, Leicester Square, London, W.C.2 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 76, Issue 1, 1 January 1964, Pages 21–39, https://doi.org/10.1111/j.1365-2133.1964.tb13970.x Published: 01 January 1964
CCR5 Antagonism in HIV Infection: Current Concepts and Future Opportunities
Authors: Timothy J. Wilkin, Roy M. Gulick
Journal: Annual Review of Medicine (2011)

CCR5 antagonists inhibit HIV-1 entry by blocking the interaction of HIV-1 with the CCR5 cellular receptor. In patients with established HIV-1 infection, some viral strains use an alternative coreceptor for HIV-1 entry, CXCR4; CCR5 antagonists are not effective in patients harboring these viral strains. Coreceptor tropism testing of viral strains in an individual patient is necessary prior to treating with a CCR5 antagonist. There is one CCR5 antagonist, maraviroc, that is FDA-approved for treatment of HIV-1 infection. This drug is used most commonly for the treatment of HIV-1 infection in patients who have failed other antiretroviral regimens. In addition to virologic effects, CCR5 antagonists are under investigation for immune-modulating effects and for HIV-1 prevention. Ongoing research will further elucidate the role of CCR5 antagonists in combating HIV disease.
HIV Seroprevalence Among Hospital Workers in Kinshasa, Zaire
Authors: Jonathan M. Mann
Journal: JAMA (1986)

A study of seroprevalence of the human immunodeficiency virus involving 2384 (96%) of Mama Yemo Hospital's (Kinshasa, Zaire) 2492 personnel found 152 (6.4%) to be seropositive. Prevalence was higher among women than among men (8.1% vs 5.2%); in women peak seroprevalence (13.9%) occurred in 20- to 29-year-olds. Workers most likely to be seropositive were those who were relatively young, those who were unmarried, those reporting a blood transfusion or hospitalization during the previous ten years, and those receiving medical injections during the previous three years. Medical, administrative, and manual workers had similar seroprevalence (6.5%, 6.4%, and 6.0%, respectively), and seropositivity was not associated with any measure of patient, blood, or needle contact. These findings are consistent with other hospital-based studies indicating low risks for occupational transmission of human immunodeficiency virus.