tbuckley/cabot-search huggingface dataset:
Genetic control of dicumarol levels in man
Authors: Elliot S. Vesell, John G. Page
Journal: Journal of Clinical Investigation (1968)

The mean half-life of dicumarol in the plasma of seven sets of identical and seven sets of fraternal twins after a single oral dose of 4 mg/kg was 43.6±SD 17.9 hr. Half-lives ranged from 7 to 74 hr in these 28 normal adults not receiving other drugs for 2 wk preceding dicumarol administration. Large differences among unrelated individuals in dicumarol half-life disappeared almost completely in identical twins, but persisted to some extent in most sets of fraternal twins. These results indicate that marked differences among subjects in dicumarol half-life are under genetic rather than environmental control. Reproducibility of values for dicumarol half-life was demonstrated. A direct relationship between the dose and the half-life of dicumarol occurred in unrelated volunteers administered progressively larger doses at 10-day intervals. Dose dependence of the half-life of a drug results in increased variability of half-life and hence in greater risks of toxicity on long-term therapy. Risks of toxicity on the one hand and of failure to anticoagulate adequately on the other can be reduced by determining dicumarol half-life before starting long-term therapy. Half-lives for dicumarol and phenylbutzone tended to be correlated in the 28 twins, but no correlation occurred between dicumarol and antipyrine half-lives.
Transcriptional analysis of HIV-specific CD8+ T cells shows that PD-1 inhibits T cell function by upregulating BATF
Authors: Michael Quigley, Florencia Pereyra, Björn Nilsson, Filippos Porichis, Catia Fonseca, Quentin Eichbaum, Boris Julg, Jonathan L Jesneck, Kathleen Brosnahan, Sabrina Imam, Kate Russell, Ildiko Toth, Alicja Piechocka-Trocha, Douglas Dolfi, Jill Angelosanto, Alison Crawford, Haina Shin, Douglas S Kwon, Jennifer Zupkosky, Loise Francisco, Gordon J Freeman, E John Wherry, Daniel E Kaufmann, Bruce D Walker, Benjamin Ebert, W Nicholas Haining
Journal: Nature Medicine (2010)
Eroding the trust
Authors: J. Foster
Journal: BMJ (1997)

Every parent worries about meningitis, especially in Gloucestershire. When 4 year old Amy developed a high temperature and headache one evening her mother, both sensible and experienced, requested a home visit. I found Amy to have no signs of meningitis and discussed the probability of a viral illness and the course that this might take. The headline in the local paper that evening, which both the parents and I had seen, referred to a local teenager who was recovering from meningitis.

In the early hours of the next day I received another request to visit Amy, as her headache had worsened. On arrival I found her condition had improved considerably following a vomit, and there was no change on examination. Parents are very much aware that general practitioners can miss early meningitis as they read about such cases in …
Identification of naïve HCV-1 patients with chronic hepatitis who may benefit from dual therapy with peg-interferon and ribavirin
Authors: Angelo Andriulli, Vito Di Marco, Maurizio Margaglione, Antonio Massimo Ippolito, Giovanna Fattovich, Antonina Smedile, Maria Rosa Valvano, Vincenza Calvaruso, Domenica Gioffreda, Michele Milella, Filomena Morisco, Martina Felder, Giuseppina Brancaccio, Massimo Fasano, Pietro Gatti, Paolo Tundo, Michele Barone, Raffaele Cozzolongo, Mario Angelico, Giovanna D’Andrea, Nicola Andriulli, Maria Lorena Abate, Giuseppe Mazzella, Giovanni Battista Gaeta, Antonio Craxi, Teresa Santantonio
Journal: Journal of Hepatology (2013)
Simultaneous echocardiographic phonocardiographic recordings at rest and during amyl nitrite administration in patients with mitral valve prolapse.
Authors: R A Winkle, D J Goodman, R L Popp
Journal: Circulation (1975)

Simultaneous electrocardiograms, phonocardiograms, and echocardiograms were recorded in 21 patients with mitral valve prolapse. Four patients with holosystolic mitral valve prolapse on echocardiogram had smaller resting end-diastolic volumes than the remaining 17 patients with late systolic echocardiopraphy prolapse (p greater than 0.01). Thirteen of the 17 patients with late systolic prolapse had phonocardiograhically recorded auscultatory phenomena. The initial vibrations of the auscultatory phenomena occurred after the onset of echocardiographic prolapse, but prior to maximal echocardiographic mitral valve prolapse. Amyl nitrite was administered to all patients. Three of the 17 patients with late systolic prolapse developed holosystolic prolapse, while the remaining 14 retained the late systolic prolapse pattern during amyl nitrite inhalation. In these 14 patients, the onset of mitral prolapse occurred earlier in systole due to decrease in the duration of systole prior to onset of mitral valve prolapse (p greater than 0.001). This corresponded with the occurrence of auscultatory phenomena earlier in systole. Twelve patients had left ventricular volumes recorded during amyl nitrite inhalation and all showed a decrease in left ventricular volumes (greater than) 0.001). These findings confirm the temporal relationship of mitral valve prolapse and onset of auscultatory phenomena in these patients. It suggests that the movement of auscultatory phenomena earlier in systole during amyl nitrite inhalation is related to earlier prolapse of the mitral valve, and that a decrease in ventricular valume is a tenable explanation for the earlier onset of prolapse.
A Psychiatric Study of Patients With Regional Enteritis
Authors: Charles V. Ford
Journal: JAMA (1969)

Obsessive-compulsive traits and unresolved dependency conflicts were prominent in 17 patients with regional enteritis studied psychiatrically and medically. These characteristics often contributed to emotional stresses which precipitated attacks. Attacks of enteritis frequently led to changes in family equilibrium which in turn alleviated or removed the original stress. Patients with regional enteritis resembled psychologically descriptions in the literature of patients with ulcerative colitis. The mothers of these patients often were dominant, obsessivecompulsive, and hypochondriacal. Other similarities included low sexual interests, rigidity and inhibition in interpersonal relationships, and comparable Minnesota Multiphasic Personality Inventory test data. Noteworthy is the fact that in enteritis patients there was a high frequency of allergies.
Genital Herpes
Authors: Te-Wen Chang
Journal: JAMA (1974)

In comparison to primary syphilis, genital herpes was seen seven times more frequently at the outpatient clinics of the New England Medical Center Hospitals. One hundred one cases were verified by virus isolation within a period of 18 months. The incubation period of initial episode of the disease varied from 3 to 14 days, with an average of five days. It was as short as 12 hours in recurrent cases. Twenty-one isolates were typed by immunofluorescent method. Eleven were type 1; ten were type 2. The unusual frequency of genital herpes due to type 1 virus is probably related to the prevalence of orogenital sex play. The overall incidence of genital herpes among all cases seen in the Skin Clinic during 1971 and 1972 was 0.8%. (<i>JAMA</i>229:544-545, 1974)
Hospitalizations and Mortality in the Lung Health Study
Authors: Nicholas R. Anthonisen, John E. Connett, Paul L. Enright, Jure Manfreda
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

This report deals with deaths and hospitalizations during the 5-year Lung Health Study, as documented by examination of appropriate records. There were 149 deaths (2.5%) during the study, caused largely by lung cancer and cardiovascular disease, particularly coronary heart disease. A total of 12.8% of participants were hospitalized, with cancer, cardiovascular disease, and nonmalignant respiratory disease accounting for 75% of hospitalizations. There were no significant differences among the original treatment groups for all-cause mortality, lung cancer, or hospitalizations for respiratory disease. Deaths and hospitalizations for cardiovascular disease and coronary artery disease were more common in the smoking intervention plus Atrovent inhaler (SI-A) group, which received ipratropium bromide, than in the smoking intervention plus placebo inhaler (SI-P) group, which received placebo, and the differences approached statistical significance. However, we were unable to find a dose effect, in that differences were not related to self-reported inhaler compliance. In the SI-A group, nine participants were hospitalized for supraventricular tachycardia as compared with two in the SI-P group, and SI-A participants with this condition were unusually compliant with their inhaled medication. When all participants were considered and smoking status considered as a time-dependent covariate, smoking cessation was associated with significant reductions in fatal or nonfatal cardiovascular disease and coronary artery disease.
Adrenaline and non-life threatening allergic reactions: Authors' reply
Authors: S. L Johnston
Journal: BMJ (2003)

Editor—We agree that adrenaline can be life saving in severe allergic reactions. In our lesson of the week we carefully stated that using adrenaline as firstline treatment in true systemic anaphylaxis is not disputed.

We also agree that identifying allergens and subsequently avoiding them are key issues in managing allergy. The incidence of life threatening anaphylaxis is, however, influenced by allergen exposure rather than adrenaline use, and we support the use of adrenaline in this context.

The message we want to convey is that adrenaline can be life saving in true systemic anaphylaxis but can be hazardous when used out of context. Correct management of localised angioedema not affecting the larynx and without hypotension or bronchospasm includes antihistamines and steroids, with careful observation for the development of systemic features, which require adrenaline. Indiscriminate use of adrenaline for non-life threatening features in patients with contraindications to treatment with adrenaline has to be questioned.

The medical emergency in case 1 was a result of adrenaline (precipitation of angina) rather than localised angioedema. Adrenaline is not a recognised treatment for urticaria and facial angioedema in the absence of systemic features. Intravenous adrenaline should be reserved for patients with immediately life threatening profound shock where appropriate monitoring facilities exist. Case 2 therefore had a life threatening complication from unnecessary adrenaline.

Both cases highlight the importance of appropriate education for and supervision of medical staff. In a study of senior house officers at the start of their accident and emergency post, 10-56% would be prepared to administer adrenaline inappropriately.1 The series of deaths reported by Pumphrey support our concerns.2

We have advised withdrawal of EpiPens only when a diagnosis of acute systemic anaphylaxis could not be substantiated and adrenaline had caused dangerous side effects.
Inhibition of Fatty Acid Synthase Attenuates CD44-Associated Signaling and Reduces Metastasis in Colorectal Cancer
Authors: Yekaterina Y. Zaytseva, Piotr G. Rychahou, Pat Gulhati, Victoria A. Elliott, William C. Mustain, Kathleen O'Connor, Andrew J. Morris, Manjula Sunkara, Heidi L. Weiss, Eun Y. Lee, B. Mark Evers
Journal: Cancer Research (2012)

Abstract Fatty acid synthase (FASN) and ATP-citrate lyase, key enzymes of de novo lipogenesis, are significantly upregulated and activated in many cancers and portend poor prognosis. Even though the role of lipogenesis in providing proliferative and survival advantages to cancer cells has been described, the impact of aberrant activation of lipogenic enzymes on cancer progression remains unknown. In this study, we found that elevated expression of FASN is associated with advanced stages of colorectal cancer (CRC) and liver metastasis, suggesting that it may play a role in progression of CRC to metastatic disease. Targeted inhibition of lipogenic enzymes abolished expression of CD44, a transmembrane protein associated with metastases in several cancers including CRC. In addition, inhibition of lipogenic enzymes and reduced expression of CD44 attenuated the activation of MET, Akt, FAK, and paxillin, which are known to regulate adhesion, migration, and invasion. These changes were consistent with an observed decrease in migration and adhesion of CRC cells in functional assays and with reorganization of actin cytoskeleton upon FASN inhibition. Despite the modest effect of FASN inhibition on tumor growth in xenografts, attenuation of lipogenesis completely abolished establishment of hepatic metastasis and formation of secondary metastasis. Together, our findings suggest that targeting de novo lipogenesis may be a potential treatment strategy for advanced CRC. Cancer Res; 72(6); 1504–17. ©2012 AACR.
O85 SHOULD WE AWAIT INTERFERON-FREE REGIMENS TO TREAT HCV GENOTYPE 1 TREATMENT-NAIVE PATIENTS? A COST-EFFECTIVENESS ANALYSIS (ANRS 12188)
Authors: S. Deuffic-Burban, M. Schwarzinger, D. Obach, V. Mallet, S. Pol, G.-P. Pageaux, V. Canva, P. Deltenre, F. Roudot-Thoraval, D. Larrey, D. Dhumeaux, P. Mathurin, Y. Yazdanpanah
Journal: Journal of Hepatology (2014)
The Endocrine Function of the Human Adrenal Cortex
Authors: Huldrick Kammer
Journal: JAMA (1980)

This book is a collection of articles presented at a symposium held in Florence, Italy, in October 1977. Its contents are almost overpowering, since it attempts to include all subject matter being researched in the laboratory concerning the hypothalamic-pituitary-adrenal interrelationship. The intended goal of the symposium has been reached, because any researcher interested in any phase of this complex subject will find in this volume a comprehensive review of important contributions made by some of the world's outstanding investigators. This book is not intended for the medical student, nor does it contain much of interest for the practicing clinical endocrinologist. Few references are made to treatment of patients. The chapters are well written, and the printing is clear. The scientific data presented as graphs and charts are informative. An outstanding feature of each chapter is an upto-date complete bibliography. This book leaves the reader with a deep feeling of respect
Pulmonary Artery Catheters
Authors: Eugene Robin
Journal: JAMA (1991)

To the Editor.—   JAMA recently published a study 1 and an editorial 2 concerning the PAC that seemed to contain a fundamental error in elementary logic and a distorted perspective concerning the nature of the responsibility of medicine for protecting patients.  The article, using a quiz, demonstrated that physician understanding of the use of the PAC is extremely variable and frighteningly low. While admitting that the efficacy of the catheter has never been adequately demonstrated and is unknown, the authors believe that more training in its use and stricter enforcement of standards should be undertaken, presumably not preceded by a prospective, randomized, controlled clinical trial.  The editorialist, while emphasizing the importance of randomized, controlled clinical trials for high-tech medicine, omits the need for such a trial to evaluate the PAC itself, disregarding the issue as to whether the net effect of the use of the catheter on patient outcome is
Management of Angiomas
Authors: Dan J. Kindel
Journal: JAMA (1960)

THE problem of the management of hemangiomas (vascular birthmarks) is an extremely common one, of great importance to the infant or child and later on to the adult as well as one of great concern to the parents. Most frequently consulted are the general practitioner, the obstetrician, the pediatrician, the surgeon, the radiologist, and the dermatologist. The larger percentage of these patients eventually find their way to the dermatologist. A most difficult decision arises for the dermatologist—to "treat" or to "watch." Primarily, dermatologists are concerned with the congenital varieties and not the acquired types associated with liver disease, pregnancy, trauma, infections, inflammatory disease, mechanical influences, and tumors. Regarding the congenital types, much confusion exists with reference to terminology, chiefly due to differences between histopathological findings and objective clinical appearance of the lesions. <h3>Port-Wine Stain</h3> The port-wine stain, also termed nevus flammeus, and capillary angioma,<sup>1</sup>hemangioma simplex,<sup>2</sup>consists of
Cardiac cycle-dependent changes in aortic area and distensibility are reduced in older patients with isolated diastolic heart failure and correlate with exercise intolerance
Authors: W.Gregory Hundley, Dalane W Kitzman, Timothy M Morgan, Craig A Hamilton, Stephen N Darty, Kathryn P Stewart, David M Herrington, Kerry M Link, William C Little
Journal: Journal of the American College of Cardiology (2001)
The Increasing Mortality Attributed to Cirrhosis and Fatty Liver, in Baltimore (1957-1966)
Authors: KARL KRAMER
Journal: Annals of Internal Medicine (1968)

A study of cirrhosis mortality among young adults (ages 25 to 44) in Baltimore between 1957 and 1966 was completed by reviewing death certificates, medical examiners' reports, and autopsy protocols. The study showed a substantial increase in cirrhosis mortality. This increase has been greatest for negro women (259.7%). Death rates were higher in negroes than in whites and in men as compared with women. Rates were also higher in lower social classes. The increase in cirrhosis mortality rates was primarily a consequence of a greater number of deaths certified by the medical examiner as being caused by cirrhosis. These certified deaths were compared with those not so certified. They were usually sudden and unexpected and occurred outside of a hospital, while those not certified occurred in a hospital and were not sudden. The principal pathologic finding in the certified deaths was a large fatty liver, while for those not certified a cirrhotic liver was the usual pathologic finding. There was little change in the death rates that were not sudden, and there was a substantial increase in the sudden-death rate.
Two levels of help for B cell alloantibody production.
Authors: D J Steele, T M Laufer, S T Smiley, Y Ando, M J Grusby, L H Glimcher, H Auchincloss
Journal: The Journal of Experimental Medicine (1996)

We have examined whether T cell stimulation by direct or indirect pathways contributes to alloantibody production by B cells after major histocompatibility complex (MHC)-disparate skin graft rejection in mice. Experiments were performed using normal mice, MHC class II-deficient mice, MHC class II-deficient mice with an intact peripheral CD4+ cell population (due to expression of class II antigens only on thymic epithelium), mice lacking the cytoplasmic tail of their MHC class II antigens, and mice depleted of CD4+ cells by anti-CD4 monoclonal antibody treatment. Depletion of recipient CD4+ cells reduced alloantibody production to barely detectable levels. Absence of donor MHC class II antigens did not affect the production of either immunoglobulin (Ig)M or IgG antibodies directed at class I alloantigens. Absence of recipient MHC class II antigens, however, led to production of only IgM but not IgG antibodies, even if the recipients had an intact CD4+ cell population. Absence of the cytoplasmic tail of the recipient's MHC class II antigens led to the production of slightly reduced amounts of IgG antibody. These findings indicate that (a) CD4+ cells are essential helper cells for B cell alloantibody production; (b) production of IgM alloantibody can occur with help from CD4+ cells, which recognize either donor class II antigens or modified recipient class II antigens; (c) isotype switching from IgM to IgG alloantibody requires help from CD4+ cells activated by antigens presented by recipient MHC class II molecules; and (d) the cytoplasmic domain of the recipient MHC class II molecules may be involved in the mechanism that leads to isotype switching by B cells. Thus, there are two levels of CD4-mediated help available for B cells responding to alloantigens: one (involving a noncognate interaction) can produce B cell activation, and a second (involving a cognate interaction) is required for differentiation and IgG alloantibody production.
Effect of smoking on Tp-e interval, Tp-e/QT and Tp-e/QTc ratios as indices of ventricular arrhythmogenesis
Authors: Hakan Taşolar, Mehmet Ballı, Mustafa Çetin, Burak Altun, Musa Çakıcı, Adil Bayramoğlu, Ömür Otlu, Hasan Pekdemir
Journal: Journal of the American College of Cardiology (2013)
Fate of the human liver after hemihepatic portal vein embolization: Cell kinetic and morphometric study
Authors: H Harada, H Imamura, S Miyagawa, S Kawasaki
Journal: Hepatology (1997)

The favorable therapeutic effect of preoperative portal vein embolization (PVE) was analyzed by assessing various volumetric, cell kinetic and morphometric parameters and examining histologically the embolized and nonembolized lobes of 15 patients who underwent extended right lobectomy 2 to 3 weeks after PVE. Each lobar volume was calculated from computed tomography (CT) images, hepatocyte proliferation was evaluated by assessing proliferative cell nuclear antigen (PCNA) expression and mitosis, hepatocyte apoptosis was evaluated by the terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and the hepatocyte numerical density as well as the sinusoidal volumetric ratio (Vvs) and the mean hepatocyte volume (Cv) were calculated using morphometric methods. PVE induced hepatocyte apoptosis and atrophy of the embolized lobe (from 798 ± 213 to 708 ± 222 cm 3 ; P &lt; .05). The increased sinusoidal volume in this lobe (17.7% ± 4.5% and 21.7% ± 5.7%, periportal and pericentral area, respectively) may have been attributable to hepatocyte deletion. Cells in the nonembolized lobe entered a highly active phase of proliferation within 2 weeks after PVE. Further evidence of cellular proliferation was provided by the increased nonembolized lobar volume (from 379 ± 132 to 545 ± 130 cm 3 ; P &lt; .01) and numerical density of hepatocyte nuclei (Nv) (5.38 ± 1.26 vs. 3.11 ± 0.85 × 10 5 /mm 3 ; P &lt; .01, nonembolized vs. embolized lobe, respectively). In conclusion, these results indicate that the favorable effect of PVE is attributable to a net gain of functional hepatocyte mass and/or early induction of hepatocyte proliferation following hepatectomy.
How to Improve the Accuracy of Diagnosis of Malignant Biliary Strictures
Authors: E. L. Fogel, S. Sherman
Journal: Endoscopy (1999)

The optimal management of patients presenting with suspected malignant biliary obstruction often requires a tissue diagnosis. Although many such patients are managed without histologic confirmation of the tumor, such a confirmation would ideally permit more accurate decision-making with reference to total patient management, including potential radiotherapy or chemotherapy. Endoscopic retrograde cholangiopancreatography (ERCP) supplies an unique opportunity to provide biliary decompression, and simultaneously to obtain a histologic or cytologic specimen from a patient with an unexplained biliary or pancreatic stricture.