tbuckley/cabot-search huggingface dataset:
THE CARDIO-VASCULAR AND RENAL RELATIONS AND MANIFESTATIONS OF GOUT.
Authors: N. S. DAVIS
Journal: JAMA (1897)

That gout and its varied complications are due to toxemia, possibly to uric acid or to other substances which vary in the blood as it does, is generally admitted. Interstitial nephritis, the common renal complication of gout, is so well understood that I need not dwell upon it in this discussion. There are a few points, however, in the course of development of the lesion to which I wish to call attention, for in most text-books and monographs sufficient emphasis is not placed upon them. It is, of all renal diseases, the most insidious in onset, and it is intermittent in progress. The kidneys are attacked now and again by uric acid or the toxic agent of gout in microscopic areas, which produce active lesions of almost microscopic size. It is true when we examine a kidney which illustrates interstitial nephritis that we find almost the whole parenchyma involved to
Vitamin D supplements do not reduce mortality risk
Authors: M. J. Bolland, A. Grey, I. R. Reid
Journal: BMJ (2014)

In their meta-analysis of 22 randomised controlled trials (RCTs), Chowdhury and colleagues report that, overall, vitamin D supplements had no effect on mortality, but a subgroup analysis suggested mortality was reduced in 14 trials of vitamin D3 and not in eight trials of vitamin D2.1 However, three of the trials classified as vitamin D3 trials actually studied calcitriol …
Letter from the Catskills.
Authors: W. B. Atkinson
Journal: JAMA (1890)

The Secretary of the American Medical Association Climbs the Catskills, Stands on Inspiration Point, Gazes into the Depths of the Kaaterskill Falls, andgives to our readers Some thoughts on Mountain Scenery and Health Combined. <h3>To the Editor:</h3> —I dare to offer to your readers from the lofty Catskills, and at about the highest point in the range, some thoughts on mountain scenery and health combined in place of a didactic or clinical lecture. The rare atmosphere united to the grand scenery gives one a feeling of exhileration which lifts him above all thoughts of disease, or its concomitant mediation. Even hygiene may almost be ignored, as health here really runs itself. We are so often treated to the phrase "the Switzerland of America" that the term seems to mean nothing, but for grandeur of mountain scenery, by which humanity lapses into nothingness, this particular portion of New York surpasses everything
Abstract 671: Identification of potent BET bromodomain inhibitors for treatment of cancer.
Authors: Sanjita Sasmal, Rajeev Kumar Shrimali, Chandrasekhar Abbineni, Kamala Kumari Arumalla, Anirudha Lakshminarasimhan, Karthikeyan Narasingapuram Arumugam, Nirbhay Kumar Tiwari, Narasimha K. Rao, Aravind AB, Subramanya Hosahalli
Journal: Cancer Research (2013)

Abstract Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression. Histone lysine acetylation is one of the most abundant epigenetic modifications central to control of gene transcription. Bromodomains are the only known readers of this specific lysine acetylation code, playing an important role in transcriptional regulation of diverse cellular processes such as inflammatory gene expression, mitosis and viral/host interactions. Recently, the human BET family bromodomains which consists of BRD2, BRD3, BRD4 and BRDT has emerged as new druggable target class for the development of specific protein interaction inhibitors, enabling a novel strategy for the development of new therapies for various diseases. Here we report the identification of potent BET bromodomain inhibitors using structure based drug design principle. Multiple distinct series of compounds have been identified with low nM potency in biochemical binding assay. Crystal structures of BRD4 in complex with hit compounds have been solved to assist in optimization. The lead compounds showed very good cell based activity and favorable ADME properties. The compounds demonstrated dose dependent inhibition of c-Myc expression confirming the mechanism of action. Further optimization of these compounds and profiling in relevant pre-clinical disease models is in progress. Citation Format: Sanjita Sasmal, Rajeev Kumar Shrimali, Chandrasekhar Abbineni, Kamala Kumari Arumalla, Anirudha Lakshminarasimhan, Karthikeyan Narasingapuram Arumugam, Nirbhay Kumar Tiwari, Narasimha K. Rao, Aravind AB, Subramanya Hosahalli. Identification of potent BET bromodomain inhibitors for treatment of cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 671. doi:10.1158/1538-7445.AM2013-671
Silent brain infarcts in adult Kuwaiti sickle cell disease patients
Authors: R. Marouf, R. Gupta, M.Z. Haider, A.D. Adekile
Journal: American Journal of Hematology (2003)

Although overt stroke is a common complication of sickle cell disease (SCD), its incidence is very low in Kuwaiti patients. On the other hand, the prevalence of silent brain infarcts, which is reported to be about 17-20% in American patients, has not been documented in adult Kuwaiti patients. This is a 1-year study of consecutive, asymptomatic SCD patients seen in the hematology clinic of Mubarak Al-Kabeer Hospital. Patients with a past history of seizure or any other neurological abnormality were excluded. The patients' charts were reviewed for frequency of hospitalizations, any documented complications, and steady-state CBC. MRI was done with a 1.5-Tesla unit with super-conducting magnet. T1- and T2-weighted sagittal and axial sections and proton-density axial images were obtained in 5-mm-thick sections. Thirty-five patients were studied, made up of 25 SS and 10 Sbeta(0)Thal, aged between 17 and 44 years, with a mean age of 26.9 +/- 9.3 years. MRI findings consistent with infarcts were found in 7 (20.0%) patients-6 SS and 1 Sbeta(0)thal-with a mean age of 31.8 +/- 8.2 years, which was significantly higher (P < 0.05) than the mean age of the unaffected group (25.1 - 9.0 years). There were also no differences in the mean Hb, Hb F, or any other hematological parameter in the two groups. Among the affected 6 SS, 2 had co-existent alpha-thal trait. It is interesting that, while silent infarcts are prevalent in young American patients, it is in the older age group that they occur in Kuwaiti patients. Further studies are needed to investigate the factors modulating this heterogeneity.
Instructional Course Lectures
Authors: James L. Hughes
Journal: JAMA (1974)

Unlike previous volumes, which included only selected lectures from the American Academy of Orthopaedic Surgeons' annual meeting, this volume includes some material presented in continuing education courses sponsored by the Academy. The editors have provided a variety of interesting topics that are discussed by authors with rich clinical and investigative experience. Though the orientation of the entire series is directed primarily toward orthopedic surgeons, a chapter written by Dr. Marshall Urist on "Osteoporosis versus Osteomalacia" provides an excellent foundation for the diagnosis and management of these problems, particularly in postmenopausal women. Anyone associated with trauma will find a remarkably thorough chapter by Drs. Peter Beck and John Collins on the posttraumatic fat embolism syndrome. A comprehensive survey of the literature by the authors provides the reader with an up-to-date summary of all aspects of this troublesome syndrome. Various authorities have collaborated to provide practical aids in the areas of fractures
Degrees in Dentistry
Authors: A. S. Underwood
Journal: BMJ (1904)

AERIAL CONVECTION OF SMALL-POX.'Si,-My experience of small-pox hospitals-and I have had charge of several-is that we shQuld hear very little of afrial convection if one important thing was attended to, that is, alteration' and enlargement of the buildings when occupied, as took place in 1902 with the hospitals under the Metropolitan Asylums Board.It is not the patients, but the constant intercourse of workmen with the towns and villages which are in close touch with the hospital.All men employed
Cholesterol Lipids of Borrelia burgdorferi Form Lipid Rafts and Are Required for the Bactericidal Activity of a Complement-Independent Antibody
Authors: Timothy J. LaRocca, Jameson T. Crowley, Brian J. Cusack, Priyadarshini Pathak, Jordi Benach, Erwin London, Juan C. Garcia-Monco, Jorge L. Benach
Journal: Cell Host & Microbe (2010)
Effectiveness of rotavirus vaccination against childhood diarrhoea in El Salvador: case-control study
Authors: O. de Palma, L. Cruz, H. Ramos, A. de Baires, N. Villatoro, D. Pastor, L. H. de Oliveira, T. Kerin, M. Bowen, J. Gentsch, D. H. Esposito, U. Parashar, J. Tate, M. Patel
Journal: BMJ (2010)

<b>Objective</b> To evaluate the effectiveness of a monovalent rotavirus vaccine against severe rotavirus disease and to assess its impact on diarrhoea in children aged less than 2 years after national introduction in El Salvador, a low-middle income country in Central America. <b>Design</b> Matched case-control study. <b>Setting</b> Seven hospitals in cities across El Salvador, January 2007 to June 2009. <b>Participants</b> 323 children aged less than 2 years admitted with laboratory confirmed rotavirus diarrhoea and 969 healthy controls matched for age and neighbourhood. <b>Main outcome measure</b> Effectiveness of rotavirus vaccination ((1–adjusted odds ratio of vaccination)×100) against rotavirus diarrhoea requiring hospital admission. <b>Results</b> Cases and controls were similar for breast feeding, premature birth, maternal education, and socioeconomic variables. G1P[8] strains were identified in 92% of rotavirus cases. Effectiveness of two doses of vaccination against diarrhoea requiring hospital admission was 76% (95% confidence interval 64% to 84%). Protection was significantly lower (P=0.046) among children aged 12 months or more (59%, 27% to 77%) compared with children aged 6-11 months (83%, 68% to 91%). One dose of vaccine was 51% (26% to 67%) effective. At the sentinel hospitals, all admissions for diarrhoea among children under 5 declined by 40% in 2008 and by 51% in 2009 from the prevaccine year 2006. <b>Conclusions</b> A monovalent rotavirus vaccine was highly effective against admissions for rotavirus diarrhoea in children aged less than 2 years in El Salvador and substantially reduced the number of such admissions in this low-middle income setting. The impact on disease epidemiology after vaccination, particularly among older children, warrants future attention.
Interleukin-6 ( <i>IL-6</i> ) and the Prognosis of Abdominal Aortic Aneurysms
Authors: K.G. Jones, D.J. Brull, L.C. Brown, M. Sian, R.M. Greenhalgh, S.E. Humphries, J.T. Powell
Journal: Circulation (2001)

Background —Abdominal aortic aneurysm is a multifactorial disorder in which inflammation is an important pathophysiological feature. In explant culture, aneurysm biopsies secrete large amounts of interleukin-6 (IL-6), and among aneurysm patients, the circulating concentration of IL-6 appears to be increased. Methods and Results —We investigated, in 19 patients, whether aneurysm wall was an important source of circulating IL-6. We also tested the hypotheses, in 466 patients with a small aneurysm, that (1) high concentrations of circulating IL-6 signaled rapid aneurysm growth and (2) the −174 G→C polymorphism in the IL-6 promoter predicted survival. For 19 patients with large or inflammatory aneurysms, the concentration of IL-6 was higher in the iliac arteries than the brachial arteries (median difference 26.5 pg/mL, this difference increasing with aneurysm diameter, P =0.01). In 466 patients with small aneurysms, the frequency of the −174 C allele (0.40) was similar to that in a normal healthy population. Patients of GG genotype had lower plasma concentrations of IL-6 than patients of GC and CC genotypes (medians 1.9, 4.8, and 15.6 pg/mL, respectively, Kruskal-Wallis P =0.047). Cardiovascular and all-cause mortalities were lower for patients of GG genotype than for patients of GC and CC genotype: hazard ratios 0.32 (95% CI 0.12 to 0.93), P =0.036, and 0.51 (95% CI 0.25 to 1.00), P =0.05, respectively. There was no association between plasma IL-6 or IL-6 genotype and aneurysm growth. Conclusions —Aortic aneurysms appear to be an important source of circulating IL-6, the concentration being influenced by genotype. For patients with small aneurysms, the −174 G→C IL-6 genotype predicts future cardiovascular mortality.
Interstate Reciprocity and Frauds in Medical Schools.
Authors: D. A. Hodghead
Journal: JAMA (1906)

San Francisco, Sept. 21, 1906. <h3>To the Editor:</h3> —September 1 you published a letter by Dr. Dudley Tait in which statements were made derogatory to the good name of the College of Physicians and Surgeons of San Francisco. Each and all of those statements that in any way reflected on the college mentioned were incorrect. Regarding this case Dr. Tait secured no information and made no effort to secure information from the college authorities. He ignored the fact that this student secured advanced standing on good and sufficient credentials, and took his required work in the summer courses which this college was then conducting. He ignored the further fact that this student was in attendance in the freshman and sophomore years. I have no desire to infringe on your space, but I ask the profession to reserve judgment until both sides are heard. To go into details here would require
Cellular immune responses against persistent hepatitis C virus: gone but not forgotten
Authors: P Klenerman
Journal: Gut (2006)

compromise the correct interpretation of these morphogenetic signals by mutating their receptors or intermediate signalling molecules.This may enable clonal growth of cancerous cells by helping them to escape the normal position dependent growth restraints that morphogenetic pathways impose.The classic examples are mutations in the Wnt pathway.The constitutive activity of Wnt signalling that results from these mutations can be inhibited by Hh signalling in colon cancer cells.Akiyoshi et al now provide the first evidence for an antagonistic interaction between the Hh and Wnt pathways in colorectal cancers in vivo and show that this interaction probably occurs at a downstream level in both pathways.
Patient participation in decision making may raise cost of care, study shows
Authors: M. McCarthy
Journal: BMJ (2013)

Increasing the participation of patients in healthcare decision making may prolong the length of stays in hospital and increase the cost of care, a new US study has found. Extrapolating the study’s results to the national scale, the researchers concluded that patient participation could cost an extra $8.7bn (£5.7bn; €6.7bn) a year.

Three other studies published online at the same time by the journal JAMA Internal Medicine showed that, though some patients wanted a bigger role in their treatment decisions, doctors often failed to explain the pros and cons of interventions or to be candid with patients about prognoses.

The first study, that showing the increased cost of decision sharing, gathered data from 21 754 patients admitted to the University of Chicago Medical Center. It found that 71% of patients said that they preferred to leave medical decisions to their physicians.1 Patients with higher educational levels and who had private insurance were more likely to say that they would like to take part in decision making. But after controlling for such factors as age, race or ethnicity, self reported health assessment, comorbidities, and admission diagnoses, the researchers found that patients keen on being involved in healthcare decision making had longer stays in hospital and higher hospital treatment costs.

Compared with the 8181 (38%) patients who had a strong desire to leave decision making in the hands of their doctors, the 6287 (29%) patients who …
P127 Improving smoking cessation advice through the implementation of a quality improvement intervention
Authors: L. Hodgson, A. Fairhurst, P. Thorburn, A. F. Frew, S. R. Doffman
Journal: Thorax (2011)

<h3>Background</h3> Smoking remains the main cause of preventable morbidity and premature death in England (DH data) and is estimated to cost the NHS £1.5 billion a year. Smoking counselling beginning during hospitalisation and including support after discharge increases smoking cessation rates (Rigotti <i>et al</i> 2008).1 Health professionals in the hospital are expected to offer cessation advice. An audit was carried out in the acute medical unit of 118 consecutive medical patients which demonstrated that only 1/25 current smokers received any cessation advice. In July 2010, driven by a quality improvement project carried out locally in patients admitted with community-acquired pneumonia, key indicators of high quality care were established, one of which was to clearly document and offer smoking cessation advice to current or recently-quit smokers. Despite being a requirement, documentation regarding smoking cessation advice was poor. In the respiratory wards, only seven patients were referred to existing smoking cessation services over 6 months. Several interventions were planned to increase awareness. No additional resource was required and members of the multidisciplinary team were employed in a variety of roles. An educational programme was established, including presentations to key specialities (acute and respiratory medicine) and key ward nursing staff. An in-reach programme was developed by the smoking cessation lead nurse, targeting wards where high rates of smoking were identified. Several foundation trainees were employed as “smoking champions,” raising awareness among their peers. <h3>Results</h3> Since initiation of the interventions, documented cessation advice has steadily risen from 0% to 68% of patients with a smoking history (see Abstract P127 figure 1). On the respiratory wards, 77 patients over 6 months (cf seven prior to intervention) were referred to the service. Four-week cessation rates in the patients referred to the cessation service was 82% and of these patients 70% had still ceased to smoke at 6 months. <h3>Conclusions</h3> Low cost, easily-deliverable interventions can act as important drivers to improve awareness and delivery of smoking cessation advice. We have demonstrated that simple strategies can be highly cost effective, of particular importance in this financial climate.
COX 2 inhibitor rejected in North America but retained in Europe
Authors: Bob Burton
Journal: BMJ (2007)

Doctors in the UK will continue to be able to prescribe the cyclo-oxygenase-2 (COX 2) inhibitor Prexige (lumiracoxib) even though it has been withdrawn from the market in Canada and the US Food and Drug Administration (FDA) has refused to approve it. 

Health Canada, the government agency with responsibility for drug registration, reviewed the safety of the 100 mg dose of lumiracoxib, following the withdrawal of the 100, 200, and 400 mg doses of lumiracoxib from the Australian market in August ( BMJ  2007;335:363 doi:10.1136/bmj.39311.635822.DB). On 4 October the department announced that it had withdrawn marketing approval of the …
Proteolytic Disassembly Is a Critical Determinant for Reovirus Oncolysis
Authors: Tommy Alain, Tom SY Kim, XueQing Lun, Adelhamid Liacini, Leslie A Schiff, Donna L Senger, Peter A Forsyth
Journal: Molecular Therapy (2007)

See page 1406Mammalian ortheoreoviruses are currently being investigated as novel cancer therapeutics, but the cellular mechanisms that regulate susceptibility to reovirus oncolysis remain poorly understood. In this study, we present evidence that virion disassembly is a key determinant of reovirus oncolysis. To penetrate cell membranes and initiate infection, the outermost capsid proteins of reovirus must be proteolyzed to generate a disassembled particle called an infectious subviral particle (ISVP). In fibroblasts, this process is mediated by the endo/lysosomal proteases cathepsins B and L. We have analyzed the early events of infection in reovirus-susceptible and -resistant cells. We find that, in contrast to susceptible glioma cells and Ras-transformed NIH3T3 cells, reovirus-resistant cancer cells and untransformed NIH3T3 cells restrict virion uncoating and subsequent gene expression. Disassembly-restrictive cells support reovirus infection, as in vitro-generated ISVPs establish productive infection, and pretreatment with poly(I:C) does not prevent infection in cancer cells. We find that the level of active cathepsin B and L is increased in tumors and that disassembly-restrictive glioma cells support reovirus oncolysis when grown as a tumor in vivo. Together, these results provide a model in which proteolytic disassembly of reovirus is a critical determinant of susceptibility to reovirus oncolysis. See page 1406 Mammalian ortheoreoviruses are currently being investigated as novel cancer therapeutics, but the cellular mechanisms that regulate susceptibility to reovirus oncolysis remain poorly understood. In this study, we present evidence that virion disassembly is a key determinant of reovirus oncolysis. To penetrate cell membranes and initiate infection, the outermost capsid proteins of reovirus must be proteolyzed to generate a disassembled particle called an infectious subviral particle (ISVP). In fibroblasts, this process is mediated by the endo/lysosomal proteases cathepsins B and L. We have analyzed the early events of infection in reovirus-susceptible and -resistant cells. We find that, in contrast to susceptible glioma cells and Ras-transformed NIH3T3 cells, reovirus-resistant cancer cells and untransformed NIH3T3 cells restrict virion uncoating and subsequent gene expression. Disassembly-restrictive cells support reovirus infection, as in vitro-generated ISVPs establish productive infection, and pretreatment with poly(I:C) does not prevent infection in cancer cells. We find that the level of active cathepsin B and L is increased in tumors and that disassembly-restrictive glioma cells support reovirus oncolysis when grown as a tumor in vivo. Together, these results provide a model in which proteolytic disassembly of reovirus is a critical determinant of susceptibility to reovirus oncolysis.
CAUSE OF GROWTH OF SARCOIDS OR OIL TUMORS
Authors: MONTROSE T. BURROWS
Journal: JAMA (1927)

It has now been well established that not only paraffin, liquid petrolatum 1 and coal tar 2 but also vegetable 3 and animal oils 4 become encapsulated when introduced into the tissues. It is also known that many of these oil tumors become active at a later time and cause pain, swelling and redness. Recently Zemansky 5 has seen a case in which quinine in olive oil had been introduced hypodermically into the fat of the buttocks during an attack of influenza, in Italy, in 1918. In 1926, one of the three tumors resulting from these injections enlarged rapidly in size and became red and painful. On examination in New York at that time, a fluctuating tumor was found and opened. It contained an oily material, but there was no definite pus. The wound refused to heal, and the lesions were excised. A typical but very cellular oil tumor was