tbuckley/cabot-search huggingface dataset:
THE ESTIMATION OF MYOCARDIAL EFFICIENCY
Authors: J. S. Goodall
Journal: BMJ (1916)

M3DWJO m 5r1These observations seem to us to be -important, first of all because they demonstrate an altered state of thle blood whliclh goes far to explain the otherwise inexplicable breatlhlessness in certain patients wlho suffer from: thle con- dition described, as irritable lheart.Tlley are important from anotlher standpoint.The temptation to cover our ignorance of the pathology of the malady as a wlhole bv referring many of its synmptomns to instability or to irrita- bility of the central nervouis system was a powerful one, so long as clear deviations from normality could not be found.Our observationls carry us from the abstract to the conierete, and tell us that we deal witlh an affection in which disordered metabolism plays a conspicuous r6le.If we are inclined lhastily to judge tlhe temper of our fellow-men, lholding that poorness of spirit alnd lack of zeaPontribute to the hlistories of plysical-inefficiency as they are related to us, sucehi findings bid uis beware, reminding us that there may be no more potent restraint to the display of spirit than tlle early conditions of ill-lhealth.
The burden of lung disease
Authors: R Hubbard
Journal: Thorax (2006)

A timely reminder of the needs of people with respiratory disease in the UK

The range of clinical conditions included under the umbrella of “respiratory medicine” is wide. From cancers to obstructive sleep apnoea, interstitial lung disease to airways disease, occupational lung disease to respiratory infections, there is a variety present in respiratory medicine not seen in other hospital based specialties. This diversity makes respiratory medicine a deeply rewarding specialty in which to work, but also means that it is not easy to quantify the full impact of lung disease on the health of the British public.

For this reason, the British Thoracic Society has produced the second edition of “ The Burden of Lung Disease ” which includes a number of statistics that may be startling to the casual reader and of interest to those involved in resource allocation in the NHS.1 For example, of the 580 000 deaths each year in the UK, one in five is due to respiratory disease with 35 000 deaths from lung cancer, 34 000 from pneumonia, and 27 000 from COPD. Respiratory disease now accounts for more than 845 000 hospital admissions each year and is second only to injury and poisoning as a cause of emergency admission to hospital. Asthma remains the …
Procalcitonin and the Early Diagnosis of Infective Endocarditis
Authors: Christian Mueller, Peter Huber, Gerd Laifer, Beat Mueller, André P. Perruchoud
Journal: Circulation (2004)

Variability in the clinical presentation of infective endocarditis (IE) makes the diagnosis a clinical challenge. We hypothesized that serum procalcitonin, a marker of systemic bacterial infection, might be helpful in its diagnosis.We conducted a prospective cohort study in 67 consecutive patients admitted to the hospital with the suspicion of IE or in whom the suspicion arose during the hospital course. IE was diagnosed by an interdisciplinary team that included an infectious disease specialist and a cardiologist who applied the Duke criteria. IE was confirmed in 21 patients. Procalcitonin was significantly higher in patients with IE (median 6.56 ng/mL) than in those with other final diagnoses (median 0.44 ng/mL, P<0.001). The area under the receiver operating characteristic curve that used procalcitonin to predict IE was 0.856 (95% CI 0.750 to 0.962), compared with 0.657 (95% CI 0.511 to 0.802) for C-reactive protein. The optimum concentration of procalcitonin for the calculation of positive and negative predictive accuracy as obtained from the receiver operating characteristic curve was 2.3 ng/mL. With this cutoff, the test characteristics of procalcitonin were as follows: sensitivity 81%, specificity 85%, negative predictive value 92%, and positive predictive value 72%. Multiple logistic regression analysis revealed that procalcitonin was the only significant independent predictor of IE on admission (OR 1.52, 95% CI 1.07 to 2.15, P=0.018).Procalcitonin may be a valuable additional diagnostic marker in patients with suspected IE.
Inducing CTLA-4–Dependent Immune Regulation by Selective CD28 Blockade Promotes Regulatory T Cells in Organ Transplantation
Authors: Nicolas Poirier, Agnes M. Azimzadeh, Tianshu Zhang, Nahzli Dilek, Caroline Mary, Bao Nguyen, Xavier Tillou, Guosheng Wu, Karine Reneaudin, Jeremy Hervouet, Bernard Martinet, Flora Coulon, Emma Allain-Launay, Georges Karam, Jean-Paul Soulillou, Richard N. Pierson, Gilles Blancho, Bernard Vanhove
Journal: Science Translational Medicine (2010)

An improved method of immunosuppression allows better immune function and prolongs the survival of transplanted organs in nonhuman primates.
Renal tubular damage detected by dynamic micro-MRI with a dendrimer-based magnetic resonance contrast agent
Authors: Hisataka Kobayashi, Satomi Kawamoto, Sang-Kyung Jo, Noriko Sato, Tsuneo Saga, Akira Hiraga, Junji Konishi, Susan Hu, Kaori Togashi, Martin W. Brechbiel, Robert A. Star
Journal: Kidney International (2002)
PREVENTION OF THE LOCALIZED AND GENERALIZED SHWARTZMAN REACTIONS BY AN ANTICOMPLEMENTARY AGENT, COBRA VENOM FACTOR
Authors: Jack S. C. Fong, Robert A. Good
Journal: The Journal of Experimental Medicine (1971)

Both localized and generalized Shwartzman reactions were induced in the same rabbits by simultaneous administration of preparatory intravenous and intradermal doses of endotoxin followed in 24 hr by the provocative dose. Control rabbits with more than 80% positive responses showed corresponding changes of platelet, white blood cell, fibrinogen, and hemolytic complement levels. Circulating fibrinogen and fibrin degradation products were detected shortly after the preparatory dose and persisted for at least 3 days. Rabbits given cobra venom anticomplementary factor showed hypocomplementemia (less than 10% of normal), leukocytosis, and elevated fibrinogen levels. After the administration of endotoxin, only one of 15 CVF-treated animals developed a Shwartzman reaction and that was mild. These rabbits showed only minor changes of platelet and fibrinogen levels throughout the experiment although their white blood cell responses were similar to those of the control group. No detectable fibrinogen and fibrin degradation products appeared in circulation, and the hemolytic complement activity increased gradually beginning with the preparatory dose of endotoxin. Thus depletion of terminal complement components (mainly C3) in rabbits is protective against the development of both localized and generalized Shwartzman reactions; its mechanism of action is probably through the sparing of platelets by inhibiting platelet-endotoxin interaction. The essential role of the complement system in Shwartzman reaction indicates that this coagulopathy probably represents a manifestation of immunologic injury.
Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis and tumorigenesis in Kaposi’s sarcoma
Authors: Diego O. Croci, Mariana Salatino, Natalia Rubinstein, Juan P. Cerliani, Lucas E. Cavallin, Howard J. Leung, Jing Ouyang, Juan M. Ilarregui, Marta A. Toscano, Carolina I. Domaica, María C. Croci, Margaret A. Shipp, Enrique A. Mesri, Adriana Albini, Gabriel A. Rabinovich
Journal: The Journal of Experimental Medicine (2012)

Kaposi’s sarcoma (KS), a multifocal vascular neoplasm linked to human herpesvirus-8 (HHV-8/KS-associated herpesvirus [KSHV]) infection, is the most common AIDS-associated malignancy. Clinical management of KS has proven to be challenging because of its prevalence in immunosuppressed patients and its unique vascular and inflammatory nature that is sustained by viral and host-derived paracrine-acting factors primarily released under hypoxic conditions. We show that interactions between the regulatory lectin galectin-1 (Gal-1) and specific target N-glycans link tumor hypoxia to neovascularization as part of the pathogenesis of KS. Expression of Gal-1 is found to be a hallmark of human KS but not other vascular pathologies and is directly induced by both KSHV and hypoxia. Interestingly, hypoxia induced Gal-1 through mechanisms that are independent of hypoxia-inducible factor (HIF) 1α and HIF-2α but involved reactive oxygen species–dependent activation of the transcription factor nuclear factor κB. Targeted disruption of Gal-1–N-glycan interactions eliminated hypoxia-driven angiogenesis and suppressed tumorigenesis in vivo. Therapeutic administration of a Gal-1–specific neutralizing mAb attenuated abnormal angiogenesis and promoted tumor regression in mice bearing established KS tumors. Given the active search for HIF-independent mechanisms that serve to couple tumor hypoxia to pathological angiogenesis, our findings provide novel opportunities not only for treating KS patients but also for understanding and managing a variety of solid tumors.
Coexistence of <i>TERT</i> Promoter and <i>BRAF</i> Mutations in Papillary Thyroid Carcinoma: Added Value in Patient Prognosis?
Authors: Miguel Melo, Adriana Gaspar da Rocha, João Vinagre, Manuel Sobrinho-Simões, Paula Soares
Journal: Journal of Clinical Oncology (2015)
Regulation of human lung epithelial cell numbers by diesel exhaust particles
Authors: H. Bayram, K. Ito, R. Issa, M. Ito, M. Sukkar, K. F. Chung
Journal: European Respiratory Journal (2006)

Particulate air pollution is associated with respiratory morbidity and has cytotoxic and pro-inflammatory effects. The effects of diesel exhaust particles (DEP) on proliferation and apoptosis of A549 lung epithelial cells were examined. When deprived of serum (serum starvation), epithelial cell numbers fell, but DEP (5–200 µg·mL −1 ) prevented this. Using flow cytometric analysis of propidium iodide (PI) staining, DEP (10 µg·mL −1 ) increased cells in the S phase of cell cycle from 12.85 to 18.75% after 48 h, reversing serum starvation-induced G 0/1 arrest. DEP also reduced the increase in apoptotic cells, as defined by double expression of annexin V/PI, observed after serum starvation (from 28.35 to 15.46%). The antioxidants, N -acetylcysteine (NAC; 33 mM) and AEOL10113 (10–100 µM), the N-terminal c-jun kinase inhibitor, SP600125 (33 µM), and nuclear factor-κB inhibitor, SN50 (33 µM), inhibited DEP-induced cell number increase. NAC inhibited DEP-induced reduction of G 0/1 and increase in cells in the S and G 2 /M phases. Expression of p21 CIP1/WAF1 mRNA and protein seen with serum starvation was reduced by DEP. In conclusion, diesel exhaust particles prevented serum starvation-led decreases in A549 epithelial cells by inducing cell cycle progression and preventing apoptosis, processes involving oxidative stress, inhibition of p21 CIP1/WAF1 expression and stimulation of N-terminal c-jun kinase and nuclear factor-κB. Therefore, low-dose diesel exhaust particle exposure may lead to lung epithelial cell hyperplasia.
Prognostic factors associated with survival in patients with symptomatic spinal bone metastases: a retrospective cohort study of 1 043 patients
Authors: L. Bollen, Y. M. van der Linden, W. Pondaag, M. Fiocco, B. P. M. Pattynama, C. A. M. Marijnen, R. G. H. H. Nelissen, W. C. Peul, P. D. S. Dijkstra
Journal: Neuro-Oncology (2014)

Expected survival is a major factor influencing extent of treatment for symptomatic spinal bone metastases (SBM). Predictive models have been developed, but their use can lead to over- or undertreatment.. The study objective was to identify prognostic factors associated with survival in patients with symptomatic SBM and to create a validated risk stratification model. All patients who were treated for symptomatic SBM between 2001 and 2010 were included in this single center retrospective study. Medical records were reviewed for type of primary cancer, performance status, presence of visceral, brain and bone metastases, number and location of spinal metastases, and neurological functioning. Performance status was assessed with the Karnofsky performance score and neurological functioning with the Frankel scale. Analysis was performed using Kaplan-Meier curves, univariate log-rank tests, Cox regression models, and Harrell's C statistic. A total of 1 043 patients were studied. The most prevalent tumors were those of breast (n = 299), lung (n = 250), and prostate (n = 215). Median follow-up duration was 6.6 years, and 6 patients were lost to follow-up. Based on the results of the uni- and multivariate analyses, 4 categories were created. Median survival in category A was 31.2 months (95% CI, 25.2–37.3 months), 15.4 months (95% CI, 11.9–18.2 months) for category B, 4.8 months (95% CI, 4.1–5.4 months) for category C, and 1.6 months (95% CI, 1.4–1.9 months) for category D. Harrell's C statistic was calculated after the model was applied to an external dataset, yielding a result of 0.69. Assessing patients according to the presented model results in 4 categories with significantly different survival times.
Irinotecan/Fluorouracil Combination in First-Line Therapy of Older and Younger Patients With Metastatic Colorectal Cancer: Combined Analysis of 2,691 Patients in Randomized Controlled Trials
Authors: Gunnar Folprecht, Matthew T. Seymour, Leonard Saltz, Jean-Yves Douillard, Hartmut Hecker, Richard J. Stephens, Timothy S. Maughan, Eric Van Cutsem, Philippe Rougier, Emmanuel Mitry, Ute Schubert, Claus-Henning Köhne
Journal: Journal of Clinical Oncology (2008)

Uncertainty exists about whether elderly patients benefit to the same extent as younger patients from combination therapy with irinotecan in the first-line treatment of metastatic colorectal cancer (CRC).Combined analysis was carried out with source data from the fluorouracil (FU)/folinic acid (FA) and the irinotecan/FU/FA arms of four first-line, phase III trials of CRC to investigate the efficacy and safety of combination and monotherapy in elderly (age > or = 70 years; n = 599) compared with younger (age < 70 years; n = 2,092) patients.Response rates were improved with irinotecan-based combination therapy compared with FU/FA in patients both younger than 70 years and > or = 70 years (46.6% v 29.0% P < .0001; and 50.5% v 30.3%, P < .0001, respectively). With irinotecan/FU/FA, progression-free survival was better for both younger (hazard ratio [HR], 0.77; 95% CI, 0.70 to 0.85; P < .0001) and elderly patients (HR, 0.75; 95% CI, 0.61 to 0.90; P = .0026). In younger patients, overall survival was improved with combination therapy (HR, 0.83; 95% CI, 0.75 to 0.92; P = .0003). The same trend was observed in elderly patients (HR, 0.87; 95% CI, 0.72 to 1.05; P = .15). There was no significant interaction between treatment arm and age in the regression analysis. The expected differences in toxicity between combination and monotherapy in elderly and younger patients were observed. A significant interaction between treatment and age (cutoff, 70 years) for vomiting and hepatotoxicity was not confirmed by analysis that used age as a continuous variable.Patients older than 70 years of age who were selected for inclusion in phase III trials derived similar benefits as younger patients from irinotecan-containing chemotherapy, and the risk of toxicity was similar.
ROENTGEN RAY INTOXICATION
Authors: S. L. Warren, G. H. Whipple
Journal: The Journal of Experimental Medicine (1923)

A single large dose of x-rays over the abdomen will cause a definite injury of the mucosa of the small intestine and the severity of the clinical intoxication seems to parallel this recognizable epithelial injury. This clinical intoxication lasts 4 to 6 days if the x-ray dose is sublethal. Subsequent doses of radiation given within this period of clinical intoxication give recognizable evidence of summation or a cumulative effect. Small but repeated doses of radiation given within a 5 or 6 day period will cause practically the same cell injury and clinical intoxication as will a single dose representing the sum of the small doses expressed in milliampere minutes. Doses of radiation given at 6 day or longer intervals show no evidence of summation. The reaction of this relatively sensitive intestinal epithelium to radiation may be similar to the reaction of certain deep lying tumor tissues to x-ray therapy and our experiments may give information of value to physicians concerned with x-ray or radium therapy.
Gene Therapy for Severe Combined Immunodeficiency
Authors: Marina Cavazzana-Calvo, Chantal Lagresle, Salima Hacein-Bey-Abina, Alain Fischer
Journal: Annual Review of Medicine (2005)

Studies of severe combined immunodeficiency (SCID), a group of rare monogenic disorders, have provided key findings about the physiology of immune system development. The common characteristic of these diseases is the occurrence of a block in T cell differentiation, always associated with a direct or indirect impairment of B cell immunity. The resulting combined immunodeficiency is responsible for the clinical severity of SCID, which, without treatment, leads to death within the first year of life. Eleven distinct SCID phenotypes have been identified to date. Mutations of ten genes have been found to cause SCID. Identifying the pathophysiological basis of most SCID conditions has led to the possibility of molecular therapy as an alternative to allogeneic hematopoietic stem cell transplantation. This review discusses recent developments in SCID identification and treatment.
Single-step QuantiFERON screening of adult contacts: a prospective cohort study of tuberculosis risk
Authors: Pranabashis Haldar, Helen Thuraisingam, Hemu Patel, Nelun Pereira, Robert C Free, James Entwisle, Martin Wiselka, Edwyn Wren Hoskyns, Philip Monk, Michael R Barer, Gerrit Woltmann
Journal: Thorax (2012)

<h3>Background</h3> The efffectiveness of tuberculosis (TB) contact screening programmes using interferon γ release assays remains uncertain as prospective contact TB risk is not well characterised. <h3>Objectives</h3> To quantify 2-year TB risk and evaluate screening performance with single-step QuantiFERON TB Gold-In Tube (QFT) in adult contacts. To compare TB risk between QFT tested subgroups stratified by exposure type (smear positive pulmonary (SP) versus non-smear positive (NSP) TB) and age (younger (16–35 years) versus older (≥36 years)). <h3>Methods</h3> Screening involved QFT testing in older contacts of SP and all younger contacts, 8–12 weeks after index notification. Chemoprevention (3RH) was offered to QFT positive (+) younger adults. TB risk was determined in a prospective cohort study. <h3>Results</h3> 43 TB events occurred in 1769 adult contacts observed for median 717 days (2-year rate (95% CI)=2·5% (1.7 to 3.2)). Index-contact strain matching was demonstrable for 18 of 22 (82%) paired samples. No contacts (0/98) receiving 3RH developed TB. 215 of 817 appropriately tested adults (26.3%) were QFT+. 14 of 112 untreated QFT+ adults developed TB (2-year rate (95% CI)=13·4% (7.7 to 21.1)). The model required 35 contacts screened with QFT to identify one contact developing TB at 2 years. TB rates were comparable in QFT+ contacts of SP and NSP (rate ratio (RR)=0.98, p=0·962). For QFT+ older contacts, the disease rate was lower (8.9% (3.3 to 19.1)) and similar to the overall group rate (RR=1.4, p=0.503). <h3>Conclusions</h3> QFT based single-step contact screening is effective in young adults.
Coagulopathy due to an acquired factor V inhibitor and subsequently thrombosis
Authors: Sushil George, M. S. Nagabhushana, Elizabeth M. Cyran
Journal: American Journal of Hematology (1995)

To the Editor: We have read with interest the letter to the Editor by Beris et al. [I], which described infection-induced transient increase in the platelet count observed only in May-Hegglin anomaly, and not in idiopathic thrombocytopenia (ITP), which may lead to the discovery of the May-Hegglin anomaly.We 121 as well as others [3-51 have demonstrated partial correction of thrombocytopenia in ITP during viral [3,5], bacterial [2,4], and Mycoplusrna [2] infections, including pneumonia, contrary to the author's comment that the partial correction of thrombocytopenia was inconsistent with ITP.Therefore, May-Hegglin anomaly cannot be differentially diagnosed between ITP on the episode of post-infection transient partial correction of thrombocytopenia.
Informed decision-making among students analyzing their personal genomes on a whole genome sequencing course: a longitudinal cohort study
Authors: Saskia C Sanderson, Michael D Linderman, Andrew Kasarskis, Ali Bashir, George A Diaz, Milind C Mahajan, Hardik Shah, Melissa Wasserstein, Randi E Zinberg, Micol Zweig, Eric E Schadt
Journal: Genome Medicine (2013)

Multiple laboratories now offer clinical whole genome sequencing (WGS). We anticipate WGS becoming routinely used in research and clinical practice. Many institutions are exploring how best to educate geneticists and other professionals about WGS. Providing students in WGS courses with the option to analyze their own genome sequence is one strategy that might enhance students' engagement and motivation to learn about personal genomics. However, if this option is presented to students, it is vital they make informed decisions, do not feel pressured into analyzing their own genomes by their course directors or peers, and feel free to analyze a third-party genome if they prefer. We therefore developed a 26-hour introductory genomics course in part to help students make informed decisions about whether to receive personal WGS data in a subsequent advanced genomics course. In the advanced course, they had the option to receive their own personal genome data, or an anonymous genome, at no financial cost to them. Our primary aims were to examine whether students made informed decisions regarding analyzing their personal genomes, and whether there was evidence that the introductory course enabled the students to make a more informed decision. This was a longitudinal cohort study in which students (N = 19) completed questionnaires assessing their intentions, informed decision-making, attitudes and knowledge before (T1) and after (T2) the introductory course, and before the advanced course (T3). Informed decision-making was assessed using the Decisional Conflict Scale. At the start of the introductory course (T1), most (17/19) students intended to receive their personal WGS data in the subsequent course, but many expressed conflict around this decision. Decisional conflict decreased after the introductory course (T2) indicating there was an increase in informed decision-making, and did not change before the advanced course (T3). This suggests that it was the introductory course content rather than simply time passing that had the effect. In the advanced course, all (19/19) students opted to receive their personal WGS data. No changes in technical knowledge of genomics were observed. Overall attitudes towards WGS were broadly positive. Providing students with intensive introductory education about WGS may help them make informed decisions about whether or not to work with their personal WGS data in an educational setting.
The problem knee. Diagnosis and treatment in the younger patient
Authors: D. S. Muckle
Journal: British Journal of Sports Medicine (1986)

This is an excellent book, not only on sports injuries but also on training, biomechanics and failures that lead to injury, on sport for the disabled, and the young, and an excellent last chapter giving in detail with photographs the exercises needed for rehabilitation.The anatomical diagrams illustrating various injuries are excellent, though a few errors in labelling have been allowed to creep in; in the figure on page 354 labelling of the talus and calcaneum have been reversed; on page 387 the trachea is labelled 'oesophagus' and on page 410 the label for the insertion of the iliopsoas is pointing to the upper third of the sartorius.We cannot blame the authors for these, nor for some uncorrected spelling mistakes, -'kilopond', not 'kilopound'l