tbuckley/cabot-search huggingface dataset:
Valve Replacement without Preoperative Cardiac Catheterization
Authors: Martin G. St. John Sutton, Marianne St. John Sutton, Paul Oldershaw, Ricardo Sacchetti, Matthias Paneth, Stuart C. Lennox, Ronald V. Gibson, Derek G. Gibson
Journal: New England Journal of Medicine (1981)

During the year 1978, the decision to perform cardiac catheterization in patients with valvular heart disease was delayed until clinical and noninvasive assessment had been completed. As a result, 184 patients underwent operation without invasive studies, and 59 had elective catheterization. Another 62 patients were referred during the same period for valve replacement after routine catheterization had been performed elsewhere. Age, sex distribution, symptoms, and cause of valve disease were similar in all three groups, although we managed emergencies and second operations more frequently without catheterization. In all patients, the preoperative diagnosis was confirmed, and no unexpected pathologic process was encountered. Operative mortality was the same in all three groups, and after two years of follow-up there was no difference in survival or symptoms. No uncorrected valve lesions became apparent in uncatheterized patients. We conclude that routine catheterization is unnecessary before valve replacement but can be reserved for specific indications in some patients. (N Engl J Med. 1981; 305:1233–8.)
Harassment Linked to Fraud, Lawsuit Alleges
Authors: Paul Cotton
Journal: JAMA (1992)

ALLEGATIONS that sexual harassment at the National Institutes of Health (NIH), Bethesda, Md, led to research fraud are now part of a federal lawsuit under the Racketeer Influenced Corrupt Organizations Act. If false, the charges are a heinous insult to highly reputable researchers. If true, they constitute perhaps the most egregious example of what some women's health advocates say is the extent to which sexual harassment can be damaging not only to the women in medicine but to the science of medicine itself. (See preceding article.) Maureen Polsby, MD, says it all started when she refused to go to bed with the man who recruited her for a medical staff fellowship at the (then) National Institutes of Neurologic and Communicative Disorders and Stroke (NINCDS), which since has been reorganized into the National Institute of Neurological Disorders and Stroke and the National Institute on Deafness and Other Communicative Disorders. Thomas Chase,
Abstract 3771: Identification of novel small molecule inhibitors of the inducible heat shock protein Hsp70
Authors: Gregor M. Balaburski, Julie Leu, Seth A. Hayik, Mark Andrake, Roland Dunbrack, Donna George, Maureen E. Murphy
Journal: Cancer Research (2011)

Abstract The stress induced molecular chaperone Hsp70 has a role in protein folding, assembly of multi-protein complexes and transport of proteins across membranes. Overall, this protein possesses significant cytoprotective and anti-apoptotic functions. High levels of Hsp70 can be found in many cancers, and these are associated with resistance to radiation and chemotherapy. Not surprisingly, overexpression of Hsp70 is generally a marker of poor patient prognosis. These combined data suggest that Hsp70, in addition to being a potential tumor prognostic marker, may also be a desirable molecular therapeutic target. 2-phenylethynesulfonamide (PES) was previously identified as a compound that inhibits apoptosis in thymocytes, by virtue of its ability to inhibit the direct p53 mitochondrial pathway. However, the mechanism of action of PES remained unknown. We recently demonstrated that PES specifically interacts with Hsp70, disrupts the interaction between Hsp70 and its co-chaperones and client proteins, and inhibits Hsp70 function at the lysosome. We further showed that PES exhibits selective toxicity to transformed cells by virtue of its ability to inhibit autophagy, a key survival pathway utilized by tumor cells. Here-in we report that we have used deletion mapping and molecular modeling to elucidate the domain of Hsp70 that interacts with PES. Additionally, to further elucidate the mechanism of action of PES, we generated and tested several analogues of PES. We find that the ability of PES to induce the death of tumor cells consistently correlates with its ability to inhibit autophagy. Further, we identified one analogue that has superior ability to induce programmed cell death in tumor cells. We are currently analyzing the efficacy and mechanism of action of this analogue in pre-clinical models. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3771. doi:10.1158/1538-7445.AM2011-3771
Transfer of public health to local authorities could leave 60 top posts vacant, survey finds
Authors: M. Limb
Journal: BMJ (2012)

Many top posts in public health in England could go unfilled in the transfer of services to local authorities, representing a “significant loss of local public health leadership,” a survey has concluded.

About a third of public health directors do not expect to transfer from the NHS to local councils from 2013, the Association of Directors of Public Health found. The association said that this could leave 50 to 60 vacant posts in the new public health structure, with a “consequent risk to public health outcomes.”

Janet Atherton, the association’s president, said that there was an urgent need to retain …
Differential expression of Bcl-2 gene family induced by transforming growth factor beta1 (TGF-beta1) is regulated by ursodeoxycholate (UDC)
Authors: Susana Sola, Pedro A. Laires, Rui E. Castro, Xiaoming Ma, Betsy T. Kren, Clifford J. Steer, Cecilia M.P. Rodrigues
Journal: Journal of Hepatology (2002)
Genetic Determinants of Emphysema Distribution in the National Emphysema Treatment Trial
Authors: Dawn L. DeMeo, Craig P. Hersh, Eric A. Hoffman, Augusto A. Litonjua, Ross Lazarus, David Sparrow, Joshua O. Benditt, Gerard Criner, Barry Make, Fernando J. Martinez, Paul D. Scanlon, Frank C. Sciurba, James P. Utz, John J. Reilly, Edwin K. Silverman
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Computed tomography (CT) scanning of the lung may reduce phenotypic heterogeneity in defining subjects with chronic obstructive pulmonary disease (COPD), and allow identification of genetic determinants of emphysema severity and distribution.We sought to identify genes associated with CT scan distribution of emphysema in individuals without alpha1-antitrypsin deficiency but with severe COPD.We evaluated baseline CT densitometry phenotypes in 282 individuals with emphysema enrolled in the Genetics Ancillary Study of the National Emphysema Treatment Trial, and used regression models to identify genetic variants associated with emphysema distribution.Emphysema distribution was assessed by two methods--assessment by radiologists and by computerized density mask quantitation, using a threshold of -950 Hounsfield units. A total of 77 polymorphisms in 20 candidate genes were analyzed for association with distribution of emphysema. GSTP1, EPHX1, and MMP1 polymorphisms were associated with the densitometric, apical-predominant distribution of emphysema (p value range = 0.001-0.050). When an apical-predominant phenotype was defined by the radiologist scoring method, GSTP1 and EPHX1 single-nucleotide polymorphisms were found to be significantly associated. In a case-control analysis of COPD susceptibility limited to cases with densitometric upper-lobe-predominant cases, the EPHX1 His139Arg single-nucleotide polymorphism was associated with COPD (p = 0.005).Apical and basal emphysematous destruction appears to be influenced by different genes. Polymorphisms in the xenobiotic enzymes, GSTP1 and EPHX1, are associated with apical-predominant emphysema. Altered detoxification of cigarette smoke metabolites may contribute to emphysema distribution, and these findings may lead to further insight into genetic determinants of emphysema.
The Difficulties of Dying
Authors: R. A. Wood
Journal: BMJ (1974)

A 47 year old man presented with a two year history of increasing cervical dysphagia, dyspnoea, and cutaneous signs. He had been diagnosed 27 years previously with Wilson9s disease and was treated with penicillamine (1.5 g daily). Systemic abnormality of elastic fibres was confirmed by light and electron microscopy following biopsy of skin, lung, oesophageal muscle, gum, pharyngeal tissue, and cervical connective tissue. Dysphagia was relieved by cricopharyngeal myotomy. Substitution of trientene dihydrochloride for penicillamine relieved cutaneous and systemic manifestations. This is possibly the first case demonstrating an association between prolonged penicillamine use and biopsy proved systemic pseudo-pseudoxanthoma elasticum. The presenting symptoms may have resulted from the abnormal numbers and properties of elastic fibres, and the changes were caused by penicillamine use, rather than by idiopathic, inherited pseudoxanthoma elasticum.
THE RATIONAL ANTISEPTIC TREATMENT OF TYPHOID FEVER.
Authors: H. A. WEST
Journal: JAMA (1897)

Probably no infectious disease has been the subject of more careful research than that of typhoid fever. There is none upon which the literature is more extensive, and about which there has been greater unanimity of opinion as to its natural history and therapeutic indications. If there is any one fact, in regard to this disease, which has been considered by all who are entitled to be regarded as authorities upon the subject as definitely settled, it is that typhoid fever belongs to the class of self-limited diseases. While various claims have been made, at different times, to the discovery of plans of treatment which are effectual in the abortion of the disease, there is no drug or combination of drugs which has received general recognition as having the power of effecting a specific cure. So, when assertions which revolutionize our conceptions of this ubiquitous and omnipresent evil are persistently
Autoimmunity risk alleles: hotspots in B cell regulatory signaling pathways
Authors: John C. Cambier
Journal: Journal of Clinical Investigation (2013)

Autoimmunity is the consequence of the combination of genetic predisposition and environmental effects, such as infection, injury, and constitution of the gut microbiome. In this edition of the JCI, Dai et al. describe the use of knockin technology to test the mechanism of action of a polymorphism in the protein tyrosine phosphatase nonreceptor 22 (PTPN22) (LYP) that is associated with susceptibility to multiple autoimmune diseases. The function of this allele, and that of a disproportionate number of autoimmune disease risk alleles, suggests that inhibitory signaling pathways that maintain B lymphocyte immune tolerance may represent an Achilles' heel in the prevention of autoimmunity.
Osteomalacia presenting as pathological fractures during pregnancy in Asian women of high socioeconomic class.
Authors: P Dandona, F Okonofua, R V Clements
Journal: BMJ (1985)

A propos de 2 observations chez des femmes asiatiques, vegetariennes, de niveau socio-economique eleve. Dans les 2 cas des douleurs donnent l'occasion de diagnostiquer des fractures passees inapercues, et une osteomalacie. Le traitement comportant de la vitamine D est efficace
Blood Culture Use in the Emergency Department in Patients Hospitalized for Community-Acquired Pneumonia
Authors: Anil N. Makam, Andrew D. Auerbach, Michael A. Steinman
Journal: JAMA Internal Medicine (2014)

sources, including prescriptions from physicians and purchases from a friend or a relative or from a drug dealer or a stranger, with greater frequency as the reported days of nonmedical use increased.Among nonmedical users reporting 200 to 365 days of use, opioid pain relievers were most often obtained via prescription from physicians (27.3%).Discussion | The overall distribution of sources for opioids used for nonmedical purposes largely reflects the behavior of the lowest-use, lowest-risk group (1-29 days), which accounts for 63.9% of the sample.However, the highest-use, highest-risk group (200-365 days) reports different sources.This group is more likely than those with the lowest frequency of use to obtain opioids from a physician's prescription or from a drug dealer.This pattern is similar to that of patients in opioid treatment programs, who cite dealers and physicians as frequent sources. 6hese results underscore the need for interventions targeting prescribing behaviors, in addition to those targeting medication sharing, selling, and diversion.The essential steps health care providers can take to curb this serious health problem include more judicious prescribing, use of prescription drug-monitoring programs, and screening patients for abuse risk before prescribing opioids.
Observations ON OSTEO-ARTHRITIS OF THE HIP
Authors: G. Parker
Journal: BMJ (1922)

OSTEO-ARTHRITIS of tlle hip, though common, is so often over- looked or mistaken for sciatica or subacute rheumatism tllat it seems worth wlhile considering its symnptoms in detail, e3pecially since its proaress and successful treatment largely dependon its early recognition.I ask attention first to a tabular classification of joint diseases, so that I may make quite clear what type of disorder it really Is.Thlle conifusion of namies in chronic joint diseases is so great that even a tentative classification may be of use.GROUP A.Traumatic arthritis.r Haemophilic arthritis.Tabetic and syringo-myelic arthritis.True gout.Heberden's nodes.Acromegalic joints.Fulmonary osteo-artihritis.Spondylitis, Type A.Osteo-arthritis multip,ex.Ostet arthrits of the hip.GRtouP B1.Purulen-t artlhritis-for example, streptococcal or pueumo- coccal join1ts.Arthritis due to typhoid and other fevers, to dysentery, diphtheria, etc.,
Molecular basis of protein S deficiency in China
Authors: Liang Tang, Xiao‐Rong Jian, Naotaka Hamasaki, Tao Guo, Hua‐Fang Wang, Xuan Lu, Qing‐Yun Wang, Yu Hu
Journal: American Journal of Hematology (2013)

Protein S (ProS) is a physiological inhibitor of coagulation with an important function in the down-regulation of thrombin generation. ProS deficiency is a major risk factor for venous thrombosis. This study enrolled 40 ProS-deficient probands to investigate the molecular basis of hereditary ProS deficiency in Chinese patients. A mutation analysis was performed by resequencing the PROS1 gene. Large deletions were identified by multiplex ligation-dependent probe amplification (MLPA) analysis. A total of 20 different mutations, including 15 novel mutations, were identified in 21 of the 40 index probands. Small mutations were detected in 18 (45.0%) probands, and large deletions were found in 3 (7.5%) probands, leaving 19 (47.5%) patients without causative variants. To evaluate the functional consequences of 2 novel missense variants, ex vivo thrombin-generation assays, bioinformatics tools, and in vitro expression studies were employed. The p.Asn365Lys ProS variant was found to have moderately impaired secretion and reduced activated protein C cofactor activity. In contrast, the p.Pro410His mutant appeared to have severely impaired secretion but full anticoagulant activity. This study is the largest investigation of ProS deficiency in China and the first investigation of the influence of Type I ProS missense mutations on the global level of coagulation function. The p.K196E mutation, which is common in the neighboring Japanese population, was not found in our Chinese population, and null mutations were common in our Chinese population but not common in Japan. Further genetic analysis is warranted to understand the causes of ProS deficiency in patients without a genetic explanation.
Connexins, Conduction, and Atrial Fibrillation
Authors: Jeffrey E. Saffitz
Journal: New England Journal of Medicine (2006)

Atrial fibrillation has always been the little sister to its ventricular counterpart — but during the past decade, it has captured our attention, mainly because it is so common. Atrial fibrillation affects nearly 2.5 million Americans, and this number could double over the next 50 years as the population ages.1 Although not the killer that ventricular fibrillation is, atrial fibrillation is by no means benign. Roughly 15 percent of strokes in the United States have been attributed to this arrhythmia.2 The pathogenesis of atrial fibrillation is complex, even as compared with the other tachyarrhythmias. Atrial fibrillation arises from dynamic interactions . . .
Colorectal cancer and rectal bleeding in primary care: Urban or rural myth?
Authors: Sanjay Purkayastha, Ara Darzi
Journal: BMJ (2006)

Editor-Walker et al show convincingly that drivers and other occupants of heavy four wheel drive vehicles are safer in crashes than those in smaller or lighter vehicles and those on foot or cycle. 1 They also show that drivers of these vehicles use mobile phones more often and seat belts less often than drivers of other cars.But by conflating mobile phone use (which distracts drivers) and non-use of seat belts (which makes drivers feel less safe) as equally important examples of illegal and dangerous practices they have sown confusion and undermined the prospect of a constructive approach to road safety.Using mobile phones and not using seatbelts have opposing consequences for other road users.The distraction caused by mobile phones increases the threat to others, but the non-use of seat belts decreases it.As the authors note, deaths of pedestrians, cyclists, and rear seat passengers increased (by 8%, 13%, and 28% respectively) after laws mandating the use of seat belts in front seats were introduced in the United Kingdom.
Animal models of emphysema: the next generations
Authors: Edward J. Campbell
Journal: Journal of Clinical Investigation (2000)

Niewoehner (1) wrote in 1988 that pulmonary emphysema is one of the most important causes of morbidity and mortality in our modern society, and his statement rings just as true today as it did then. Progress in the intervening years has built on the creation and analysis of animal models for this disease, many of which, including the one described by Zheng et al. (2) in a recent issue of the JCI, exploit technology that could not have been imagined at that time.

Animal models are especially important for slowly progressing diseases such as pulmonary emphysema (3). They facilitate the understanding of complex pathogenetic relationships and allow hypothesis testing. They also have the potential to allow tests of preventive therapies that would be inordinately time consuming or ethically forbidden in humans. A review of past and future generations of animal models will place the contribution of Zheng and colleagues in perspective.
Effect of peripheral cardiopulmonary bypass on left ventricular size, afterload and myocardial function during elective supported coronary angioplasty
Authors: Gregory S. Pavlides, Andrew M. Hauser, Robert K. Stack, Patricia I. Dudlets, Cindy Grines, Gerald C. Timmis, William W. O'Neill
Journal: Journal of the American College of Cardiology (1991)
Photosensitive dermatitis induced by flutamide
Authors: M. Fujimoto, K. Kikuchi, S. Imakado, M. Furue
Journal: British Journal of Dermatology (1996)

Journal Article Photosensitive dermatitis induced by flutamide Get access M. Fujimoto, M. Fujimoto Department of Dermatology, Tokyo University Branch Hospital, Tokyo, Japan Search for other works by this author on: Oxford Academic Google Scholar K. Kikuchi, K. Kikuchi Department of Dermatology, Tokyo University Branch Hospital, Tokyo, Japan Search for other works by this author on: Oxford Academic Google Scholar S. Imakado, S. Imakado Department of Dermatology, Tokyo University Branch Hospital, Tokyo, Japan Search for other works by this author on: Oxford Academic Google Scholar M. Furue M. Furue Department of Dermatology, Tokyo University Branch Hospital, Tokyo, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 135, Issue 3, 1 September 1996, Pages 496–497, https://doi.org/10.1111/j.1365-2133.1996.tb01532.x Published: 01 September 1996
STUDIES ON THE ENDOPLASMIC RETICULUM
Authors: George E. Palade, Keith R. Porter
Journal: The Journal of Experimental Medicine (1954)

A series of representative cell types including avian fibroblasts, and macrophages; rabbit mesothelia, endothelia, and nephron epithelia; and rat glandular epithelia (parotid) were studied comparatively in vitro and in situ with the electron microscope. Cells in vitro were examined in whole mounts and in sections whereas cells in situ were observed exclusively in sections. It was found that an endoplasmic reticulum similar to that previously described in cultured material is present in situ in all cell types examined. Modifications in its appearance introduced by the sectioning technique were discussed and explained. The observations showed in addition that the endoplasmic reticulum is a network of cavities which may enlarge into relatively vast, flattened vesicles here described as cisternae.
BFM-oriented treatment for children with acute lymphoblastic leukemia without cranial irradiation and treatment reduction for standard risk patients: results of DCLSG protocol ALL-8 (1991–1996)
Authors: WA Kamps, JPM Bökkerink, FGAJ Hakvoort-Cammel, AJP Veerman, RS Weening, ER van Wering, JF van Weerden, J Hermans, R Slater, E van den Berg, WG Kroes, A van der Does-van den Berg
Journal: Leukemia (2002)
The Treatment of Angina Pectoris with Griseofulvin
Authors: N. P. DePasquale
Journal: JAMA (1963)

BECAUSE of its fungistatic properties griseofulvin (Grisactin) is widely used in the treatment of many types of dermatomycoses in patients of all ages. Recently, an elderly patient with severe angina pectoris was noted to experience marked relief of his angina pectoris while receiving griseofulvin for the treatment of dermatomycosis. This finding was of sufficient interest to prompt us to evaluate the usefulness of griseofulvin in the treatment of other patients with angina pectoris. The beneficial results have been so striking as to justify this report. <h3>Material and Methods</h3> Griseofulvin in the form of micronized particles was administered to ten patients with angina pectoris and ischemic heart disease secondary to coronary arteriosclerosis. All of the patients were under the care of various physicians at the Charity Hospital Medical Clinic. They were receiving coronary vasodilators in the form of glyceryl trinitrate and one of the long-acting nitrate preparations. Diet and activity were