tbuckley/cabot-search huggingface dataset:
The Biology and Clinical Relevance of the <i>PTEN</i> Tumor Suppressor Pathway
Authors: Isabelle Sansal, William R. Sellers
Journal: Journal of Clinical Oncology (2004)

Genetic alterations targeting the PTEN tumor suppressor gene are among the most frequently noted somatic mutations in human cancers. Such lesions have been noted in cancers of the prostate and endometrium and in glioblastoma multiforme, among many others. Moreover, germline mutation of PTEN leads to the development of the related hereditary cancer predisposition syndromes, Cowden disease, and Bannayan-Zonana syndrome, wherein breast and thyroid cancer incidence is elevated. The protein product, PTEN, is a lipid phosphatase, the enzymatic activity of which primarily serves to remove phosphate groups from key intracellular phosphoinositide signaling molecules. This activity normally serves to restrict growth and survival signals by limiting activity of the phosphoinositide-3 kinase (PI3K) pathway. Multiple lines of evidence support the notion that this function is critical to the ability of PTEN to maintain cell homeostasis. Indeed, the absence of functional PTEN in cancer cells leads to constitutive activation of downstream components of the PI3K pathway including the Akt and mTOR kinases. In model organisms, inactivation of these kinases can reverse the effects of PTEN loss. These data raise the possibility that drugs targeting these kinases, or PI3K itself, might have significant therapeutic activity in PTEN-null cancers. Akt kinase inhibitors are still in development; however, as a first test of this hypothesis, phase I and phase II trials of inhibitors of mTOR, namely, rapamycin and rapamycin analogs are underway.
Human Subjects in Medical Experimentation: A Sociological Study of the Conduct and Regulation of Clinical Research
Authors: William M. Cooper
Journal: JAMA (1975)

This book by Bradford Gray will be a landmark for the clinical researchers in academic medicine. He has documented objectively the problem in communication and the discrepancies between standards and practice in the conducting of clinical research. The book comes across as a scientific evaluation, done by an individual sympathetic to medicine and clinical investigation who finds glaring defects in the mechanisms now utilized for protecting the individual and his rights. The paternalism of the medical profession and conflict between ethics and the career interests of the investigators in the academic system are highlighted by the findings of the study. There is no alternative but to admit we have done a poor job in actual performance despite meeting proper paper requirements. The author makes some definite recommendations for improving communication between investigator and subject and the monitoring, by the Clinical Research Committee, of the experimental process and the individual's rights.
THE ORIGIN OF MONOCYTES IN CERTAIN LYMPH NODES AND THEIR GENETIC RELATION TO OTHER CONNECTIVE TISSUE CELLS
Authors: Claude E. Forkner
Journal: The Journal of Experimental Medicine (1930)

1. The theories for the origin of monocytes from myeloblasts, lymphocytes, endothelium, macrophages, and primitive cells are reviewed and considered. 2. Monocytes in all stages of development have been demonstrated to be present constantly in large numbers in all the lymph nodes of the body, except in the large mesenteric group. 3. The relations of these cells to undifferentiated cells, lymphocytes, macrophages, plasma cells, and endothelium are described. 4. The origin of adult monocytes from primitive undifferentiated cells through the stages of monoblasts and pre-monocytes is described and illustrated. 5. The demonstration in certain lymph nodes of innumerable monocytes in all stages of development permits of a shifting of the term "monoblast" from a more or less theoretical name to its proper place as a term designating that particular cell which is derived from a primitive undifferentiated cell and which is the immediate precursor of the pre-monocyte. 6. The term "pre-monocyte" is proposed to designate the intermediate stage between the monoblast and the mature monocyte. 7. Evidence is advanced to show that monocytes are an independent strain of cells, but that under physiological conditions they may be transformed into macrophages, this representing at least one way in which the latter cells normally are produced. 8. In no organs or tissues other than in certain specific lymph nodes, chiefly the peripheral group, can one constantly find monocytes in all stages of development. 9. Developing monocytes occasionally may be found in small numbers in the spleen, mesenteric lymph nodes, Peyer's patches, subcutaneous connective tissues, lungs, and omenta of normal rabbits, but their presence is by no means constant and their numbers are insignificant in comparison with those found in the peripheral lymph nodes. 10. Monocytes and pre-monocytes do not stain by the common methods used for the demonstration of the reticulo-endothelial system and therefore must be considered for the present as independent of this system, except in so far as monocytes may be transformed into macrophages. 11. Plasma cells, stained with the supravital technique, as seen in lymph nodes, are described. No basis has been found for the theory that plasma cells and monocytes are closely related structural elements.
Early identification and management of chronic kidney disease in adults: summary of updated NICE guidance
Authors: S. Carville, D. Wonderling, P. Stevens
Journal: BMJ (2014)

The publication of an internationally accepted definition and classification of chronic kidney disease (CKD) 12 years ago precipitated a proliferation of research and literature surrounding the identification of CKD, risk factors for progression, and important prognostic factors.1 It also stimulated continuing debate concerning the criteria used for definition of CKD and exactly how ageing influences CKD and its sequelae.2 3 The National Institute for Health and Care Excellence (NICE) has modified its previous recommendations on the classification of CKD,4 partly based on Kidney Disease Improving Global Outcomes (KDIGO)5 and driven by prognostic data from large observational studies. NICE has also recognised a requirement for better identification of people at risk of adverse outcome and covers some key areas relating to the management of CKD, including frequency of monitoring, progression of CKD, acute kidney injury, and renin-angiotensin system blockade. This article summarises the most recent recommendations from NICE.6 NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Investigations for chronic kidney disease
Understanding MeSH for Literature Searches-Reply
Authors: Octo Barnett
Journal: JAMA (1995)

<h3>In Reply.</h3> —It was not our intention to suggest that one should use only MeSH when searching MEDLINE. While there are many circumstances in which this approach will produce acceptable results, there are, as Mr Fremer points out, circumstances when one needs to also search the MEDLINE Title and Abstract fields. A general strategy might be to search first using MeSH terms, review the citations retrieved, and if it is felt that the retrieval is incomplete, then to repeat the search using a combination of MeSH and free-text terms. While no indexing system is perfect, it is generally accepted that the National Library of Medicine's indexing of MEDLINE with MeSH "probably represents the state of the art in manually indexed databases."<sup>1</sup> Dr Darmoni states that MeSH check tags are mandatory. However, they are mandatory only in the sense that the indexer must scan every article for the tag's applicability,
The Gynecology of Childhood and Adolescence.
Authors: Vincent J. Capraro
Journal: Annals of Internal Medicine (1968)

Here for the first time the physician interested in gynecologic problems in children and adolescents, be he pediatrician, gynecologist, general practitioner, or other specialist, can find most of the current thinking in this fast-developing field. This work of 574 pages is the most extensive book on the subject, and since 40% of the population in the United States is less than 18 years of age, it is quite timely.  The relevant literature, culled by Dr. Huffman, has been condensed to dovetail with the author's tremendous experience and vast clinical knowledge. Some chapters have a bibliography of over 200 references, and can serve as a source of the latest information in pediatric and adolescent gynecology. There is a good balance between practical diagnostic and therapeutic points and theoretic and etiologic considerations. The background pathology is very well covered.  The book is logically divided and proper space is given to such areas
Nasal oxygen in exacerbations of ventilatory failure: an underappreciated risk.
Authors: R. J. Davies, J. M. Hopkin
Journal: BMJ (1989)

FIG 2 -Cost of the annual retention fee of the General Medical Council more problems than it solves.A solution may therefore lie not in actively seeking coverage on the basis of professional public relations advice, but in being more flexibly responsive to situations where the GMC can usefully do so.After two hours of supplemental oxygen at 2 1/min her arterial oxygen tension was 15 1 kPa (table I).When she was breathing normal air the oxygen flow rate was
CASE of GALL STONES: CHOLECYSTOTOMY: Hour-Glass Contraction of the Gall Bladder
Authors: H. C. Donald
Journal: BMJ (1898)

KIMICAL~~~~~~~~~~~~~~~~~~~~~~~~~J b"L occurred between the ages of io and 20 years, and in io cases the attack was the first.These patients were generally ad- mitted in extremis, with a history of from three to eight days' illness.The abdomen was opened in 8 cases, and ia the others the diagnosis was verified or made at the necropsy.In conclusion, taking all the cases together, the usual sym- ptoms were fairly constant.In 3 cases pain and swelling were more marked on the left side, and in 8 cases pain was complained of during micturition.Concretions were recorded in 12 instances (5 in Class c), and in I case the appendix came away as a slough three days after an abscess was opened.A faecal fistula resulted in 3 cases, and a ventral hernia in 2.
The Antibiotic Paradox: How Miracle Drugs Are Destroying the Miracle
Authors: Stuart M. Polly
Journal: JAMA (1993)

"Mr. Williams came in last night. It looks like secondary staph pneumonia, with septic emboli. The ward team has him on vancomycin, ceftriaxone, ampicillin-sulbactam, and ciprofloxacin until the cultures are back." And so it goes: patient after patient on high-dose, multidrug therapy, for infections caused by progressively resistant microorganisms. Seeing this and similar patients on a daily basis brings home the truth of<i>The Antibiotic Paradox</i>. Dr Stuart B. Levy's new book describes the "antibiotic age," from the use of penicillin in survivors of the Coconut Grove fire in 1942, through the development of antimicrobial resistance, to a frightening future in which antibiotics as we know them today may be obsolete. Dr Levy is an internationally recognized expert on resistance and an outspoken critic of the widespread misuse of antibiotics. He is president of the Alliance for Prudent Use of Antibiotics, an international organization founded in 1981 to collect and
Nobel prize is awarded for work leading to “knockout mouse”
Authors: Geoff Watts
Journal: BMJ (2007)

The award of the 2007 Nobel prize in physiology or medicine to three gene technologists has been widely applauded by biologists. They believe that the three scientists' achievements will play a major part in revealing the extent of genetic influences in human disease.

Rather less enthusiastic is the animal rights lobby. The work for which Mario Capecchi, Martin Evans, and Oliver Smithies were awarded the prize led to the development of the quaintly but aptly named “knockout mouse.” Now an essential tool of laboratory research into the role of genes, its creation reversed a fall in the number of experiments carried out each year on animals.

The Nobel citation talks of the trio's discovery of “principles for introducing specific gene …
Selenomethionine Se 75 Thymus Scans in Myasthenia Gravis
Authors: Robert J. Cowan
Journal: JAMA (1971)

Of 20 patients with myasthenia gravis studied with selenomethionine Se 75 mediastinal scans, two (10%) had positive scans. Both of these patients underwent surgery with removal of a thymoma. Since this radiopharmaceutical is accumulated in numerous tissues, false-positive studies may present some difficulty. The adult thymus, in the absence of a thymoma, does not appear to concentrate selenomethionine Se 75 sufficiently for external scanning. Negative studies may therefore be of value in ruling out the presence of a thymoma.
Use of Smokeless Tobacco Among Adolescents
Authors: Earl J. Berman
Journal: JAMA (1986)

<h3>To the Editor.—</h3> The recently published American Medical Association report, "Tobacco Product Liability," stated that there are no national data on teenage chewing tobacco use.<sup>1</sup>However, there have been several regional reports of adolescent smokeless tobacco use based on self-report data. These have indicated use rates ranging between 10% and 40%.<sup>1-3</sup>Recently, we conducted a study at two senior high schools, one urban and the other suburban, involving a total of 296 students and using a self-report questionnaire. It is known that the self-reporting of smoking is a sensitive subject for high school students and that significant underreporting is common.<sup>4</sup>To overcome this, smoking researchers use validation techniques such as the "bogus pipeline."<sup>4,5</sup>In this technique, students are told that their tobacco use responses will be validated by measuring saliva thiocyanate levels. Saliva specimens are then collected but not chemically processed. This is the first reported
Drug Metabolism in the Newborn
Authors: Margareta Eriksson, Sumner J. Yaffe
Journal: Annual Review of Medicine (1973)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Elevated C-Reactive Protein Levels and Impaired Endothelial Vasoreactivity in Patients With Coronary Artery Disease
Authors: Stephan Fichtlscherer, Gunter Rosenberger, Dirk H. Walter, Susanne Breuer, Stefanie Dimmeler, Andreas M. Zeiher
Journal: Circulation (2000)

Background —Elevated C-reactive protein (CRP) serum levels, an exquisitely sensitive objective marker of inflammation, relate to long-term prognosis in patients with coronary artery disease and in apparently healthy men. Because abnormalities of endothelial regulation of vascular function may contribute to the occurrence of coronary events, we tested the hypothesis that elevated CRP levels are associated with an abnormal systemic endothelial vascular reactivity. Methods and Results —Endothelium-dependent (10 to 50 μg/min acetylcholine) and endothelium-independent (2 to 8 μg/min sodium nitroprusside) forearm blood flow responses were measured with venous occlusion plethysmography in 60 male patients with angiographically documented coronary artery disease. Forearm blood flow responses to acetylcholine were inversely correlated with CRP serum levels ( r =−0.46, P =0.001). With multivariate analysis that included the classic risk factors for coronary artery disease, elevated CRP serum level remained a statistically significant independent predictor of a blunted endothelial vasodilator capacity. Most important, normalization of elevated CRP levels over time was associated with a normalization of endothelium-mediated forearm blood flow responses after 3 months. Conclusions —Thus, elevated CRP serum levels indicative of a systemic inflammatory response are associated with a blunted systemic endothelial vasodilator function. The identification of elevated CRP levels as a transient independent risk factor for endothelial dysfunction might provide an important clue to link a systemic marker of inflammation to atherosclerotic disease progression.
Cumulative Trauma Disorders of the Upper Extremities-Reply
Authors: David M. Rempel
Journal: JAMA (1992)

<h3>In Reply.</h3> —Dr Bohr's detailed comments on diagnostic methods for various entrapment neuropathies are welcome. More research is needed and is being directed at the diagnostic methods and management of these disorders, but much remains unknown. We attempted to draw conclusions that would help the general practitioner. We agree with Dr Bohr that it is probably best to use either the term "ulnar neuropathy at the elbow" or "ulnar nerve entrapment at the elbow" rather than the more specific and more widely used term "cubital tunnel syndrome." There are several causes of ulnar nerve entrapments at the elbow; entrapment at the cubital tunnel is one.<sup>1</sup>Pronator syndrome should not be considered a wastebasket diagnosis. It occurs, but accurate diagnosis of this condition is not easy.<sup>1</sup> The diagnostic tests for CTS or cervical root syndromes were not proposed to be used in isolation in a clinical evaluation. No single
Spectrin modifications in a heterozygous case of both hereditary elliptocytosis and β‐thalassemia
Authors: Sara Streichman, Ethy Herz, Ilana Tatarsky
Journal: American Journal of Hematology (1990)

Abstract The clinical and hematological parameters of a patient described here, who inherited the genes of both hereditary elliptocytosis (HE) and β‐thalassemia, seem to reflect a mutual enhancement of the two diseases. The coexistence of the two pathologies is probably also responsible for the observed changes in spectrin: the appearance of an extra spectrin band between tetramers and dimers on denaturing gel electrophoresis and the metabolic‐dependent reduction in spectrin amount. It is assumed that the instability of the skeletal network that results from the HE pathology caused increased exposure of the spectrin molecule to oxidative damage that usually occurs in thalassernic red cells. The products of such oxidation may have led to abnormal spectrin associations which finally resulted in the above changes.
THE PHYSICIAN'S INVESTMENTS
Authors: RUKEYSER MERRYLE STANLEY
Journal: JAMA (1927)

Physicians have long since freed themselves from the traditions of myth and magic in their own professional activities, but as investors they are still prone to place faith in the supernatural. If medical men would bring their scientific, questioning attitude into the field of finance, they would tend to cease to remain favorites on the sucker lists of security charlatans. Inexperienced outside the biologic sciences, physicians are frequently thwarted by naively assuming that the casual lay outsider is equipped to give them financial information that will lead on to fortune. Sure thing tips on the stock market are on a par with "patent medicines" and quack remedies; they fulfil a human demand by promising much, but in the long run they are likely to yield only frustration and disappointment. In this age of specialization, the medical man cannot afford to become a specialist in finance. But he can be consistent with the
The Abciximab ST-Recovery on AMI (ASTRONAMI) GUSTO V substudy: enhanced early speed, stability, and quality of reperfusion with anti-pletelet augmented thrombolytic therapy for ST-elevation AMI
Authors: Mitchell W. Krucoff, Cynthia L. Green, Anatoly Langer, Brian Gibler, Paul W. Armstrong, Kathleen M. Trollinger, Suzanne W. Crater, Michael A. Lincoff, Robert M. Califf, Eric J. Topol
Journal: Journal of the American College of Cardiology (2002)
High-Resolution Imaging of Resolved Central Serous Chorioretinopathy Using Adaptive Optics Scanning Laser Ophthalmoscopy
Authors: Sotaro Ooto, Masanori Hangai, Atsushi Sakamoto, Akitaka Tsujikawa, Kenji Yamashiro, Yumiko Ojima, Yoshihiko Yamada, Hideo Mukai, Susumu Oshima, Takashi Inoue, Nagahisa Yoshimura
Journal: Ophthalmology (2010)
Postmenopausal Breast Cancer Is Associated with Exposure to Traffic-Related Air Pollution in Montreal, Canada: A Case–Control Study
Authors: Dan L. Crouse, Mark S. Goldberg, Nancy A. Ross, Hong Chen, France Labrèche
Journal: Environmental Health Perspectives (2010)

Only about 30% of cases of breast cancer can be explained by accepted risk factors. Occupational studies have shown associations between the incidence of breast cancer and exposure to contaminants that are found in ambient air.We sought to determine whether the incidence of postmenopausal breast cancer is associated with exposure to urban air pollution.We used data from a case-control study conducted in Montreal, Quebec, in 1996-1997. Cases were 383 women with incident invasive breast cancer, and controls were 416 women with other incident, malignant cancers, excluding those potentially associated with selected occupational exposures. Concentrations of nitrogen dioxide (NO2) were measured across Montreal in 2005-2006. We developed a land-use regression model to predict concentrations of NO2 across Montreal for 2006, and developed two methods to extrapolate the estimates to 1985 and 1996. We linked these estimates to addresses of residences of subjects at time of interview. We used unconditional logistic regression to adjust for accepted and suspected risk factors and occupational exposures.For each increase of 5 ppb NO2 estimated in 1996, the adjusted odds ratio was 1.31 (95% confidence interval, 1.00-1.71). Although the size of effect varied somewhat across periods, we found an increased risk of approximately 25% for every increase of 5 ppb in exposure.We found evidence of an association between the incidence of postmenopausal breast cancer and exposure to ambient concentrations of NO2. Further studies are needed to confirm whether NO2 or other components of traffic-related pollution are indeed associated with increased risks.
Cardiac monitoring in a regional hospital.
Authors: J. R. Forbes, P. R. Evans
Journal: BMJ (1969)

BEDICALJOURNAL(tetracycline and nystatin) was prescribed.The pain subsided, but the right scrotum started to swell.On arrival at hospital the boy did not com- plain of any pain in the scrotum.There was no history of any urinary trouble.His pulse was normal and his temperature 99 8°F. (37-7°C.).There was oedema of the right half of the scrotum, extending to the left side.The scrotum was extremely tender.The right testis was higher in the scrotum and no distinc- tion could be made out between it and the epididymis.The urine was normal chemically.A diagnosis of torsion was made and im- mediate operation carried out.Through a scrotal incision the testis was exposed and was found to be dark blue.There was high investment of the tunica vaginalis and torsion was intravaginal.As the testis did not improve after release of torsion, orchidectomy was done.The left testis was exposed at the same operation and high investment of the tunica vaginalis was found on this side too ; therefore orchidopexy was done.A histological report showed haemorrhagic infarct and necrotic spermatic tubules.