tbuckley/cabot-search huggingface dataset:
Breaking bad news
Authors: Liam Farrell
Journal: BMJ (2001)

Breaking bad news is quite all right with me; as La Rochefoucald said, “We all have strength enough to bear the troubles of others.” However, I often try to soften the blow with the gift of music: “Your Auntie Rose is dead,” sung to the tune of “Happy Birthday”; or the gift of humour: “You have two months to live, gosh, but that was from last month, and this is February”; or the gift of charades, which is tricky, as medical terms don't lend …
Regulation of iron homeostasis in anemia of chronic disease and iron deficiency anemia: diagnostic and therapeutic implications
Authors: Igor Theurl, Elmar Aigner, Milan Theurl, Manfred Nairz, Markus Seifert, Andrea Schroll, Thomas Sonnweber, Lukas Eberwein, Derrick R. Witcher, Anthony T. Murphy, Victor J. Wroblewski, Eva Wurz, Christian Datz, Guenter Weiss
Journal: Blood (2009)
A Noncanonical, GSK3-Independent Pathway Controls Postprandial Hepatic Glycogen Deposition
Authors: Min Wan, Karla F. Leavens, Roger W. Hunter, Shlomit Koren, Alexander von Wilamowitz-Moellendorff, Mingjian Lu, Santhosh Satapati, Qingwei Chu, Kei Sakamoto, Shawn C. Burgess, Morris J. Birnbaum
Journal: Cell Metabolism (2013)
Where the latest US dietary guidelines are heading
Authors: Daan Kromhout
Journal: BMJ (2015)

So farewell dietary cholesterol and total fat as risk factors worth worrying about

Recently, the US Dietary Guidelines Advisory Committee released its recommendations for the next edition of Dietary Guidelines for Americans .1 Two notable conclusions of the committee have attracted particular attention2 3: the elimination of dietary cholesterol as a “nutrient of concern” and the absence of a limit on total fat consumption. The committee’s pronouncements will reverse nutrition policy because the low cholesterol, low fat diet has been the cornerstone of public health nutrition since 1980. In this editorial I will review the evidence for this change in policy from a historical perspective. 

The low cholesterol, low fat diet for preventing heart attacks was popularised in the first part of the 20th century. Classic animal experiments showed that feeding rabbits excessive cholesterol induced lipid containing lesions in the aorta. Anitschkow hypothesized that a high plasma cholesterol concentration caused atherosclerosis and its complications.4 Observant medical doctors from the Netherlands noticed extraordinarily low numbers of patients with myocardial infarction in the East Dutch Indies (Cornelis de Langen) and China (Isodore Snapper).5 The diets of these …
Siah: A Promising Anticancer Target
Authors: Christina S.F. Wong, Andreas Möller
Journal: Cancer Research (2013)

Siah ubiquitin ligases play important roles in a number of signaling pathways involved in the progression and spread of cancer in cell-based models, but their role in tumor progression remains controversial. Siah proteins have been described to be both oncogenic and tumor suppressive in a variety of patient cohort studies and animal cancer models. This review collates the current knowledge of Siah in cancer progression and identifies potential methods of translation of these findings into the clinic. Furthermore, key experiments needed to close the gaps in our understanding of the role Siah proteins play in tumor progression are suggested.
Effects of Chemoradiation on Tumor-Host Interactions: The Immunologic Side
Authors: Silvia C. Formenti, Sandra Demaria
Journal: Journal of Clinical Oncology (2008)

Their comprehensive review ofthe available clinical evidence compels the reader to abandon thisinvestigational paradigm.Wewouldliketosuggestanadditionalhypothesistoexplaintheconsistentlyinferiorresultswhenneoadjuvantplatinum-basedchem-otherapy precedes radiation or a chemoradiotherapy regimen com-paredwithaﬁrst-lineapproachofconcurrentchemoradiation.Preclinical and clinical evidence support an immune-mediatedcomponent as part of the process of tumor cell death induced byradiotherapy and the most common chemotherapy agents.
Small-intestinal mucosal abnormalities in various skin diseases fact or fancy?
Authors: J. Marks, S. Shuster
Journal: Gut (1970)

Two-thirds of patients with dermatitis herpetiformis have been found to have a flat or convoluted mucosa but no special association has been found in the other dermatoses studied with structural alterations in the small bowel mucosa. The frequency distribution of the predominant and individual small intestinal mucosal features is the same in the patients in the present series with eczema, psoriasis, and rosacea as in the local control population. A predominantly convoluted mucosa has been found in the upper small intestine in 8% of these patients and in 8% of subjects without a rash. The presence of convolutions in patients with these dermatoses is merely a reflection of the incidence in the normal population of Newcastle upon Tyne. Different findings in the same skin disease in different parts of the country are explicable on the basis of variations in the normal mucosa between one geographical region and another. The increased incidence of a convoluted mucosa in the north east of England requires further study to determine whether it is indicative of an increased incidence of the coeliac syndrome in the region, or whether it results from a minor population difference or a local peculiarity of diet.
Revaccination with BCG: its effects on skin tests in Kuwaiti senior school children
Authors: M A Shaaban, M Abdul Ati, G M Bahr, J L Standford, D N Lockwood, I C McManus
Journal: European Respiratory Journal (1990)

Following a policy of BCG vaccination adopted in Kuwait more than 20 yrs ago, children receive their first vaccination just before starting school. Those who have a response of less than 10 mm induration to 2 tu of RT23 PPD, when they are 13 yrs old, are revaccinated. The effects of this revaccination on skin test positivity in a group of 18 yr old senior school children have been investigated. In a random study group 23% were found to have received BCG a second time. Revaccination resulted in a significant increase in positivity to tuberculin, and to the other 6 reagents tested, that was much more than would have been expected due to the passage of time alone in low responders. Scars of the second BCG vaccination were larger than those after the first vaccination, and showed a sex difference, with scars being significantly larger in boys than in girls. Boys also tended to show the largest responses to skin tests, with the notable exception of tuberculin to which girls showed the largest response. In most cases responses to skin tests were larger after revaccination than after a single vaccination. Based on this study, it is impossible to be sure that revaccination improved protective immunity, but the increase in tuberculin responsiveness, and recognition of environmental mycobacterial species may be indirect evidence supporting this conclusion.
Expression of vascular remodeling markers in relation to bradykinin receptors in asthma and COPD
Authors: Fabio L.M. Ricciardolo, Federica Sabatini, Valentina Sorbello, Dirkje S. Postma, Wim Timens, Antonino Di Stefano
Journal: European Respiratory Journal (2013)

Vascular remodeling plays a central role in asthma and COPD. Bradykinin (BK) is a vasoactive peptide involved in asthma. We studied the role of angiogenic factors in relation to BK receptors in asthma and COPD. Bronchial biopsies from 33 COPD, 24 old asthmatics (OA), 18 old control smokers (OCS), 11 old control non-smokers (OCNS), 15 young asthmatics and 10 young control non-smokers were immunostained for CD31, VEGF, angiogenin (ANG) and BK receptors (B2R and B1R). Fibroblast co-localization of relevant molecules was performed by immunofluorescence. BK-induced ANG release was studied (ELISA) in bronchial fibroblasts from asthma.  In bronchial lamina propria of OA, CD31+ and VEGF+ cells were more than in OCNS (p
Identification of anticitrullinated protein antibody reactivities in a subset of anti-CCP-negative rheumatoid arthritis: association with cigarette smoking and HLA-DRB1 ‘shared epitope’ alleles
Authors: Catriona A Wagner, Jeremy Sokolove, Lauren J Lahey, Camilla Bengtsson, Saedis Saevarsdottir, Lars Alfredsson, Michelle Delanoy, Tamsin M Lindstrom, Roger P Walker, Reuven Bromberg, Piyanka E Chandra, Steven R Binder, Lars Klareskog, William H Robinson
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Introduction</h3> A hallmark of rheumatoid arthritis (RA) is the development of autoantibodies targeting proteins that contain citrulline. Anticitrullinated protein antibodies (ACPAs) are currently detected by the commercial cyclic citrullinated peptide (CCP) assay, which uses a mix of cyclised citrullinated peptides as an artificial mimic of the true antigen(s). To increase the sensitivity of ACPA detection and dissect ACPA specificities, we developed a multiplex assay that profiles ACPAs by measuring their reactivity to the citrullinated peptides and proteins derived from RA joint tissue. <h3>Methods</h3> We created a bead-based, citrullinated antigen array to profile ACPAs. This custom array contains 16 citrullinated peptides and proteins detected in RA synovial tissues. We used the array to profile ACPAs in sera from a cohort of patients with RA and other non-inflammatory arthritides, as well as sera from an independent cohort of RA patients for whom data were available on carriage of <i>HLA-DRB1</i> 'shared epitope' (SE) alleles and history of cigarette smoking. <h3>Results</h3> Our multiplex assay showed that at least 10% of RA patients who tested negative in the commercial CCP assay possessed ACPAs. Carriage of <i>HLA-DRB1</i> SE alleles and a history of cigarette smoking were associated with an increase in ACPA reactivity—in anti-CCP<sup>+</sup> RA and in a subset of anti-CCP<sup>−</sup> RA. <h3>Conclusions</h3> Our multiplex assay can identify ACPA-positive RA patients missed by the commercial CCP assay, thus enabling greater diagnostic sensitivity. Further, our findings suggest that cigarette smoking and possession of <i>HLA-DRB1</i> SE alleles contribute to the development of ACPAs in anti-CCP<sup>−</sup> RA.
Longitudinal Perceptions of Prognosis and Goals of Therapy in Patients With Metastatic Non–Small-Cell Lung Cancer: Results of a Randomized Study of Early Palliative Care
Authors: Jennifer S. Temel, Joseph A. Greer, Sonal Admane, Emily R. Gallagher, Vicki A. Jackson, Thomas J. Lynch, Inga T. Lennes, Connie M. Dahlin, William F. Pirl
Journal: Journal of Clinical Oncology (2011)

Understanding of prognosis among terminally ill patients impacts medical decision making. The aims of this study were to explore perceptions of prognosis and goals of therapy in patients with metastatic non-small-cell lung cancer (NSCLC) and to examine the effect of early palliative care on these views over time.Patients with newly diagnosed metastatic NSCLC were randomly assigned to receive either early palliative care integrated with standard oncology care or standard oncology care alone. Participants completed baseline and longitudinal assessments of their perceptions of prognosis and the goals of cancer therapy over a 6-month period.We enrolled 151 participants on the study. Despite having terminal cancer, one third of patients (46 of 145 patients) reported that their cancer was curable at baseline, and a majority (86 of 124 patients) endorsed getting rid of all of the cancer as a goal of therapy. Baseline perceptions of prognosis (ie, curability) and goals of therapy did not differ significantly between study arms. A greater percentage of patients assigned to early palliative care retained or developed an accurate assessment of their prognosis over time (82.5% v 59.6%; P = .02) compared with those receiving standard care. Patients receiving early palliative care who reported an accurate perception of their prognosis were less likely to receive intravenous chemotherapy near the end of life (9.4% v 50%; P = .02).Many patients with newly diagnosed metastatic NSCLC hold inaccurate perceptions of their prognoses. Early palliative care significantly improves patient understanding of prognosis over time, which may impact decision making about care near the end of life.
Continuous administration of cefotaxime at exacerbation of COPD
Authors: Sudheer Vinnamala
Journal: Thorax (2007)

▴ van Zanten ARH, Oudijk M, Nohlmans-Paulssen MKE, et al . Continuous vs intermittent cefotaxime administration in patients with chronic obstructive pulmonary disease and respiratory tract infections: pharmacokinetics/ pharmacodynamics, bacterial susceptibility and clinical efficacy. Br J Clin Pharm2007;63:100–9.

[OpenUrl][1][CrossRef][2][PubMed][3]



This randomised prospective non-blinded study compared the pharmacokinetics, pharmacodynamics, antibiotic resistance and clinical efficacy of continuous vs intermittent administration of cefotaxime in 93 patients with chronic obstructive pulmonary disease (COPD) requiring hospitalisation for moderate to severe community acquired exacerbations (GOLD stages 2–4). Forty-seven patients received 2 g of cefotaxime as a continuous infusion over 24 h plus a …

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Treatment of Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue Type With Cladribine: A Phase II Study
Authors: Gerald Jäger, Peter Neumeister, Ruth Brezinschek, Thomas Hinterleitner, Wolfgang Fiebiger, Melitta Penz, Hans J. Neumann, Brigitte Mlineritsch, Maria DeSantis, Franz Quehenberger, Andreas Chott, Christine Beham-Schmid, Gerald Höfler, Werner Linkesch, Markus Raderer
Journal: Journal of Clinical Oncology (2002)

PURPOSE: As chemotherapy has not been extensively studied in patients with lymphoma of the mucosa-associated lymphoid tissue (MALT), we initiated a prospective study to evaluate the activity of the nucleoside analog cladribine (2-chlorodeoxyadenosine [2-CdA]) in this disease. PATIENTS AND METHODS: Patients with histologically verified MALT-type lymphoma were enrolled. 2-CdA was administered at a dose of 0.12 mg/kg body weight on 5 consecutive days, as a 2-hour infusion. Cycles were repeated every 4 weeks for a maximum of six cycles. RESULTS: Nineteen patients with gastric and seven patients with extragastric MALT lymphoma were enrolled. All patients were chemotherapy-naive, and two had been locally irradiated before systemic relapse of the lymphoma. A total of 102 cycles was administered to our patients (median number of cycles per patient, four). All 25 assessable patients responded to treatment: 21 patients (84%) achieved complete remission (CR) and four patients achieved partial remission. All patients (100%) with gastric presentation, but only three patients (43%) with extragastric presentation, achieved CR. Toxicities were moderate and mainly hematologic and required dose reduction and/or premature discontinuation of therapy in only three cases. Two patients died from vascular events, one shortly after the first cycle because of myocardial infarction and the other from stroke 3 months after the second course. Three patients relapsed after 13, 18, and 22 months and one patient showed progressive disease after 15 months. At present, 24 patients are alive at a median follow-up time of 32 months. CONCLUSION: Our data demonstrate that 2-CdA is highly effective in inducing CR in 84% of patients with MALT-type lymphoma.
Sensorimotor changes and functional performance in patients with knee osteoarthritis
Authors: M. V Hurley, D. L Scott, J. Rees, D. J Newham
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> Muscles are essential components of our sensorimotor system that help maintain balance and perform a smooth gait, but it is unclear whether arthritic damage adversely affects muscle sensorimotor function. Quadriceps sensorimotor function in patients with knee osteoarthritis (OA) was investigated, and whether these changes were associated with impairment of functional performance. <h3>METHODS</h3> Quadriceps strength, voluntary activation, and proprioceptive acuity (joint position sense acuity) were assessed in 103 patients with knee OA and compared with 25 healthy control subjects. In addition, their postural stability, objective functional performance (the aggregate time for four activities of daily living), and disabilities (Lequesne index) were also investigated. <h3>RESULTS</h3> Compared with the control subjects, the patients with knee OA had weaker quadriceps (differences between group mean 100N, CI 136, 63N), poorer voluntary activation (20% CI 13, 25%) that was associated with quadriceps weakness, and impaired acuity of knee joint position sense (1.28°, CI 0.84, 1.73°). As a group the patients were more unstable (p=0.0017), disabled (10, CI 7, 11), and had poorer functional performance (19.6 seconds, CI 14.3, 24.9 seconds). The most important predictors of disability were objective functional performance and quadriceps strength. <h3>CONCLUSIONS</h3> In patients with knee OA, articular damage may reduce quadriceps motoneurone excitability, which decreases voluntary quadriceps activation thus contributing to quadriceps weakness, and diminishes proprioceptive acuity. The arthrogenic impairment in quadriceps sensorimotor function and decreased postural stability was associated with reduced functional performance of the patients.
Activation of the Ischemic Ventricle and Acute Peri-Infarction Block in Experimental Coronary Occlusion
Authors: LOYAL L. CONRAD, T. EDWARD CUDDY, ROBERT H. BAYLEY
Journal: Circulation Research (1959)

Changes in left ventricular activation during the first 10 min. following occlusion of the anterior descending branch of the left coronary artery of dogs were studied by using multiple intramural electrodes. Intramural block and an increase in the amplitude of R were observed routinely in the outermost layers of muscle in the central zone of maximal ischemia as long as the occlusion was maintained. The changes were distinct from those produced by left bundle-branch block. Failure to propagate the accession process in normal fashion seems to be characteristic of ischemic heart muscle.
c-Fms and the αvβ3 integrin collaborate during osteoclast differentiation
Authors: Roberta Faccio, Sunao Takeshita, Alberta Zallone, F. Patrick Ross, Steven L. Teitelbaum
Journal: Journal of Clinical Investigation (2003)

beta(3) integrin-null osteoclasts are dysfunctional, but their numbers are increased in vivo. In vitro, however, the number of beta(3)(-/-) osteoclasts is reduced because of arrested differentiation. This paradox suggests cytokine regulation of beta(3)(-/-) osteoclastogenesis differs in vitro and in vivo. In vitro, additional MCSF, but not receptor activator of NF-kappaB ligand (RANKL), completely rescues beta(3)(-/-) osteoclastogenesis. Similarly, activation of extracellular signal-regulated kinases (ERKs) and expression of c-Fos, both essential for osteoclastogenesis, are attenuated in beta(3)(-/-) preosteoclasts, but completely restored by additional MCSF. In fact, circulating and bone marrow cell membrane-bound MCSFs are enhanced in beta(3)(-/-) mice, correlating with the increase in the osteoclast number. To identify components of the MCSF receptor that is critical for osteoclastogenesis in beta(3)(-/-) cells, we retrovirally transduced authentic osteoclast precursors with chimeric c-Fms constructs containing various cytoplasmic domain mutations. Normalization of osteoclastogenesis and ERK activation, in beta(3)(-/-) cells, uniquely requires c-Fms tyrosine 697. Finally, like high-dose MCSF, overexpression of c-Fos normalizes the number of beta(3)(-/-) osteoclasts in vitro, but not their ability to resorb dentin. Thus, while c-Fms and alpha(v)beta(3) collaborate in the osteoclastogenic process via shared activation of the ERK/c-Fos signaling pathway, the integrin is essential for matrix degradation.
The signal functions of early infant crying
Authors: Joseph Soltis
Journal: Behavioral and Brain Sciences (2004)

In this article I evaluate recent attempts to illuminate the human infant cry from an evolutionary perspective. Infants are born into an uncertain parenting environment, which can range from indulgent care of offspring to infanticide. Infant cries are in large part adaptations that maintain proximity to and elicit care from caregivers. Although there is not strong evidence for acoustically distinct cry types, infant cries may function as a graded signal. During pain-induced autonomic nervous system arousal, for example, neural input to the vocal cords increases cry pitch. Caregivers may use this acoustic information, together with other cues, to guide caregiving behavior. Serious pathology, on the other hand, results in chronically and severely abnormal cry acoustics. Such abnormal crying may be a proximate cause of adaptive infant maltreatment, in circumstances in which parents cut their losses and reduce or withdraw investment from infants with low survival chances. An increase in the amount of crying during the first few months of life is a human universal, and excessive crying, or colic, represents the upper end of this normal increase. Potential signal functions of excessive crying include manipulation of parents to acquire additional resources, honest signaling of need, and honest signaling of vigor. Current evidence does not strongly support any one of these hypotheses, but the evidence is most consistent with the hypothesis that excessive early infant crying is a signal of vigor that evolved to reduce the risk of a reduction or withdrawal of parental care.