tbuckley/cabot-search huggingface dataset:
Essential Hypertension
Authors: DONALD J. BRESLIN, RAY W. GIFFORD, JOHN F. FAIRBAIRN
Journal: Circulation (1966)

THIS follow-up study was undertaken to clarify the natural history of essential hypertension.Information of this type is in- dispensable to evaluation of therapy for this disease.Keith, Wagener, and Barker' in 1939 dem- onstrated the value of their classification of hypertensive changes in the retina as an aid to prognosis in hypertensive patients.However, the number of patients with milder forms of hypertension in that series was small and the study covered a period of less than 10 years.Consequently, we thought that a more exten- sive investigation of the prognostic value of ophthalmoscopic findings and other criteria would be desirable. Material and MethodThis study was based on 631 cases in which essential hypertension was first diagnosed at the Mayo Clinic in 1940.The follow-up period was at least 5 years in 557 cases and at least 20 years in 540.An attempt was made to obtain follow-up information for all patients with group-3 or group- 4 hypertension.However, to prevent the number of cases of group-i and group-2 hypertension from becoming unwieldy, follow-up information was sought from every patient in these categories who was seen in the first 6 months of 1940 and from only every third patient who was seen in the last 6 months of 1940.Patients with a systolic blood pressure of 160 mm.Hg or more or with a diastolic pressure of 90 mm. or more, or with both, were considered hypertensive.Only 17 patients in the entire series failed to have at least one recorded dias- tolic-blood-pressure reading of 90 mm. or more, and all these had a systolic pressure in excess of 160 mm.Of the 540 patients traced for at least From the Mayo Clinic and Mayo Foundation, Rochester, Minnesota.The Section on Biometry and Medical Statistics, Mayo Clinic, gave helpful advice and provided the statistics that appear in this paper.
Congenital Hemolytic Anemia Associated with Dehydrated Erythrocytes and Increased Potassium Loss
Authors: Bertil E. Glader, Normand Fortier, Maurice M. Albala, David G. Nathan
Journal: New England Journal of Medicine (1974)

A 21-year-old woman was found to have congenital hemolytic anemia characterized by dehydrated-appearing erythrocytes in the peripheral blood. The red-cell sodium was increased, potassium was decreased, and the cell water content was reduced. No metabolic or hemoglobin abnormalities were detected to account for this cation distribution. The basic defect appeared to be increased membrane permeability to cations that was greater for potassium than for sodium. Consequently, these cells lost potassium in excess of sodium gained, the total cell cation content decreased, and rigid, osmotically resistant desiccytes (dehydrated erythrocytes) were formed as water left the cells in response to the decreased solute concentration. Clinically, this patient has done well in spite of persistent hemolysis. Her three-year-old son also has congenital hemolytic anemia with the same clinical abnormalities, including a marked decrease in red-cell potassium. Whereas previous studies have demonstrated that permeability abnormalities can lead to water-loaded cells and hemolysis, our findings indicate that cellular dehydration may also produce hemolytic anemia. (N Engl J Med 291:491–496, 1974)
Outcome of Capsule Endoscopy in Determining Indication and Route for Push-and-Pull Enteroscopy
Authors: G Gay, M Delvaux, I Fassler
Journal: Endoscopy (2006)

Background and Study Aim: Video capsule endoscopy and push-and-pull enteroscopy (PPE), both allow a complete examination of the small bowel in patients with suspected intestinal disorders. Due to the invasiveness of PPE, indications should probably be selective. The aim of the present prospective study was to evaluate the outcome of an approach whereby capsule endoscopy was used to select patients in whom PPE was indicated. Patients and Methods: 164 patients were included (90 men; age 54 ± 18 years) with various indications for small-bowel investigation, such as obscure bleeding (n = 88), suspected Crohn’s (n = 14) or celiac (n = 12) disease, or known or strongly suspected localized diseases such as neoplasms (n = 18) for biopsy. Four patients with a suspected intestinal stenosis underwent PPE without prior capsule endoscopy. In the remaining 160 patients, who had a capsule endoscopy, PPE was selected if there were lesions requiring biopsy or angiodysplasias to be treated by argon plasma coagulation (APC). Regarding the insertion route, an anal PPE was indicated if the capsule transit time from ingestion to arrival at the lesion was ≥ 75 % of the total time from ingestion to arrival at the cecum. After gut cleansing, PPE was performed with general anesthesia, and the small bowel was examined until the lesion was reached or the scope could not be advanced further. If the suspected lesion had not been reached, a second procedure was performed through the alternative route, under the same conditions. Results: The diagnostic yield of capsule endoscopy was 75 %. According to the indications, 47 PPE procedures were performed in 42 patients, including 33 through the oral route, 4 through the anal route and 5 combined ones. Indications were: suspicion of intestinal tumor (n = 13), celiac disease with chronic bleeding (n = 4), suspicion of Crohn’s disease (n = 3), treatment of significant arteriovenous malformations (AVMs) (n = 10), diffuse enteropathies (n = 3), nonsteroidal anti-inflammatory drug (NSAID)-related conditions (n = 2), and obscure digestive bleeding (n = 3). Lesions detected by capsule endoscopy were reached by PPE in all but two cases. The positive predictive value (PPV) of capsule endoscopy to make a correct indication for PPE was 94.7 % and the negative predictive value (NPV) was 98.3 %. The PPV and NPV of a time index of > 0.75 to start via the anal route were 94.7 % and 96.7 %. No complications were observed and all patients were discharged the day after the procedure. Follow-up at 9 months showed that capsule endoscopy followed by PPE had positively influenced the management of 90.5 % of the patients. Conclusions: The use of capsule endoscopy as a filter for PPE results in effective management of patients with various intestinal diseases. Capsule endoscopy can also direct the choice of route of PPE; a time index of > 0.75 appears to reliably indicate an anal route so that a double procedure is required in only about 12 % of cases.
Abstract 959: Attenuation of hypoglycemia-associated resistance to PI103 and KU63794 through their synergistic combination in PIK3CA-mutant gastric cancer cells.
Authors: Bhaskar Bhattacharya, Sarah Low, Meiqi Yee, King Xin Koh, Richie Soong
Journal: Cancer Research (2013)

Abstract Drug testing in vitro has traditionally been performed in hyperglycemic culture conditions, yet many tumours and their microenvironments are hypoglycemic. Hypoglycemia could contribute to drug resistance through many mechanisms such as activation of stress and survival pathways, and by altering tumour bioenergetics. The aim of this study was to evaluate if hypoglycemia reduces drug sensitivity, and test strategies to attenuate any resistance. Two gastric cancer (GC) cells with PIK3CA mutations (AGS, HGC27) and two without (MKN45, NUGC4) were cultured in routine high glucose (HG) (25mM) or low glucose (LG) (5mM) DMEM. The IC50s of PI103 (PI3K/mTOR inhibitor), and KU63794 (mTOR inhibitor) were measured at 72h using MTS assay. Protein and cell cycle analysis were performed by ELISA and PI/RNase staining respectively. Combination analysis was performed using combination index (CI) method of Chou and Talalay. Cells with mutant (mt) but not wildtype (wt) PIK3CA displayed significant resistance to both PI103 and KU63794 in LG compared to HG conditions (Table 1), despite having similar doubling times and cell cycle profiles. Basal protein analysis revealed increased p-mTOR, p-S6, p-4EBP1 and GLUT1 in PIK3CA mt cells grown in LG compared to HG conditions. The levels of these proteins did not differ in PIK3CA wt cells, in addition to p-Akt in all cells. The activation of the mTOR pathway prompted the testing of the combination of PI103 and KU63794. The combination was synergistic in AGS and HGC27 cells (CI=0.09, p=0.012 and CI=0.13, p=0.032 respectively) in LG conditions, and additive in HG conditions. Furthermore, synergy was associated with significant reduction in p-4EBP1 and extracellular lactate concentration. No synergy was seen in the wt cell lines. These results suggest that hypoglycemia can reduce drug sensitivity, and that resistance to PI103 and KU63794 in hypoglycemic conditions can be circumvented by combining the two agents. Table 1. IC50 (μM) of PI103 and KU63794 in HG and LG conditions, * p &amp;lt; 0.01 Cell Line PIK3CA PI103 (HG) PI103 (LG) KU63794 (HG) KU63794 (LG) AGS Mutant 0.90 ± 0.02 7.2 ± 1.4* 0.5 ± 0.03 18.1 ± 1.3* HGC27 Mutant 0.45 ± 0.01 6.8 ± 0.4* 0.37 ± 0.01 20.1 ± 2.4* NUGC4 Wildtype 21.3 ± 4.7 22.4 ± 3.8 8.7 ± 6.5 6.9 ± 7.9 MKN45 Wildtype 1.8 ± 0.9 2.3 ± 1.8 3.4 ± 0.8 2.4 ± 0.6 Citation Format: Bhaskar Bhattacharya, Sarah Low, Meiqi Yee, King Xin Koh, Richie Soong. Attenuation of hypoglycemia-associated resistance to PI103 and KU63794 through their synergistic combination in PIK3CA-mutant gastric cancer cells. [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 959. doi:10.1158/1538-7445.AM2013-959
Abstract 2418: Investigating p53 and other potential determinants of cell sensitivity to ATR inhibition by VE-821
Authors: Fiona K. Middleton, Tao Chen, John R. Pollard, Nicola J. Curtin
Journal: Cancer Research (2014)

Abstract Background: Defects in the multifactorial DNA damage response (DDR) are common in cancer, making them vulnerable to inhibitors of other components of the DDR. ATR is a key component of the DDR, signalling ssDNA, arising from stalled replication forks, resected double strand breaks (DSBs) and NER intermediates to activate cell cycle arrest at the S/G2 checkpoints and initiate homologous recombination repair (HRR). Tumors often have a dysfunctional G1 checkpoint e.g. due to p53 mutations or other DDR defects. ATR inhibition of the S/G2 checkpoints and HRR has the potential to exploit these defects and selectively target cancer. VE-821 is a potent ATR inhibitor under advanced pre-clinical investigation Hypotheses: 1) Cells with dysfunctional p53 will be more sensitive to ATR inhibition. 2) Defects in other DDR components will sensitise cells to ATR inhibition. Methods: The survival of isogenic p53 mutant/null and wt/corrected human cell lines (HCT116 p53+/+ and p53-/- or U2OS p53WT and p53DN (dominant negative)) and a panel of repair defective Chinese hamster ovary and lung fibroblast cells was determined using colony formation after 24 hours exposure VE-821 alone or in the presence of gemcitabine or ionising radiation. Results: There was no significant difference in sensitivity to VE-821 between p53 wt or mutant/null cells in either HCT116 (LC50 = 2.13 and 4.56 µM, respectively) or U2OS pairs (LC50 = 2.54 and 3.34 µM, respectively). However, 1 µM VE-821 significantly potentiated the antimetabolite, gemcitabine, in HCT116 p53-/- (4.3-fold) but not p53+/+ cells (1.5-fold), and enhanced cell kill by 100 nM gemcitabine 40-fold in U2OS p53DN cells but only 3-fold in U2OS p53WT cells. Chinese hamster ovary cells defective in XRCC1 (single stranded break repair) were more sensitive to single agent VE-821 than the parental wt cells (35% and 55% survival at 10 µM, respectively). Data on other repair-defective cell lines will be presented. Conclusions: p53 status is not a determinant of sensitivity to VE-821 as a single agent but VE-821 preferentially sensitises cells lacking functional p53 to gemcitabine. This supports the hypothesis that p53 status may be predictive of cellular response to ATR inhibition in combination with certain chemotherapies. Furthermore, data using Chinese hamster cell lines indicate that DDR defects may be exploited by ATR inhibition. Citation Format: Fiona K. Middleton, Tao Chen, John R. Pollard, Nicola J. Curtin. Investigating p53 and other potential determinants of cell sensitivity to ATR inhibition by VE-821. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2418. doi:10.1158/1538-7445.AM2014-2418
Inhibitory KIR/HLA incompatibility between sexual partners confers protection against HIV-1 transmission
Authors: Wim Jennes, Sonja Verheyden, Julie W. Mertens, Makhtar Camara, Moussa Seydi, Tandakha N. Dieye, Souleymane Mboup, Christian Demanet, Luc Kestens
Journal: Blood (2012)
Self-deceiving intentions
Authors: Mike W. Martin
Journal: Behavioral and Brain Sciences (1997)

Contrary to Mele's suggestion, not all garden-variety self-deception reduces to bias-generated false beliefs (usually held contrary to the evidence). Many cases center around self-deceiving intentions to avoid painful topics, escape unpleasant truths, seek comfortable attitudes, and evade self-acknowledgment. These intentions do not imply paradoxical projects or contradictory belief states.
Efficacy and Safety of a New Prolonged Release Formulation of Alfuzosin 10 mg Once Daily versus Alfuzosin 2.5 mg Thrice Daily and Placebo in Patients with Symptomatic Benign Prostatic Hyperplasia
Authors: P. van Kerrebroeck, A. Jardin, K.U. Laval, P. van Cangh
Journal: European Urology (2000)
Abstract 2856: Functional profile of BEZ-235 activity in human tumor primary culture microspheroids by <i>ex vivo</i> analysis of programmed cell death (EVA/PCD)
Authors: Robert Alan Nagourney, Paula J. Bernard, Federico R. Francisco, Steven S. Evans
Journal: Cancer Research (2012)

Abstract Aberrant signaling through the phospho-inositol pathway via the gain of PI3K function or loss of PTEN is a hallmark of many malignancies. Drugs that inhibit this pathway offer novel therapeutic opportunities. The imidazoquinolone derivative, BEZ-235, reversibly inhibits signaling through PI3K &amp; mTOR by competition at ATP binding sites. We used ex vivo analysis of programmed cell death (EVA/PCD) to examine the activity and clinical potential of BEZ 235 in human tumors isolated from 88 surgical tumor specimens. By interrogating drug effects in primary culture micro-spheroids, replete with vascular, stromal and inflammatory elements, the EVA/PCD platform can provide insights into cellular responses under native-state conditions. Lethal concentration 50% values (LC50's), interpolated from dose response curves, were used to compare the activity of BEZ-235 by diagnosis using modified Z-scores. Comparisons between BEZ activity and related inhibitors of PI3K (LY294002), mTOR (Everolimus) &amp; AKT (Phen B15-kindly provided by Dr. Peter Houghton) were conducted by Pearson-Moment. By rank order, BEZ-235 activity revealed upper gastrointestinal, breast, NSCLC and hematological malignancies to have the most favorable profiles, while renal, ovarian, colon and sarcoma specimens fell in the more resistant range. Pearson moments revealed high correlation coefficients (R values) for LY294002=0.56 (P =0.001); Everolimus=0.51 (P= 0.005) &amp; Phen B15=0.89(P= 0.005) all consistent with BEZ-235's known modes of action. As PI3K signaling is associated with inhibition of apoptosis, its up-regulation may confer collateral resistance to other stressors like growth factor withdrawal or cytotoxic drugs. Relationships between BEZ-235 and other classes of drugs are being examined to explore additional correlations and potential combination that could provide future therapeutic opportunities, as will be reported. Supported in part by the Vanguard Cancer Foundation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2856. doi:1538-7445.AM2012-2856
Service Dogs for People With Severe Ambulatory Disabilities
Authors: Susan L. Duncan
Journal: JAMA (1996)

To the Editor.  —The study by Drs Allen and Blascovich1on evaluating use of service dogs for people with severe ambulatory disabilities will be extremely important for many people who have disabilities.  Service animals2have been trained in this country for approximately 80 years, beginning with guide dogs for people with visual impairments. In the last 20 years, the role of service dogs has expanded to include alerting people who are deaf or hard of hearing to the presence of specific sounds, providing the type of mobility work described in the article by Allen and Blascovich, anecdotal reports of dogs sensing and alerting their owners to oncoming seizures, and providing emotional support to people with mental or emotional disabilities.  Trainers of service dogs have never developed a common language, professional credentialing, or enforceable standards that are uniformly applied to every trainer or service dog or to the education
Effects of bone marrow derived mesenchymal stem cells transplantation in acutely infarcting myocardium
Authors: Hainan Piao, Tae‐Jin Youn, Jin‐Sook Kwon, Young‐Hwa Kim, Jang‐Whan Bae, None Bora‐Sohn, Dong‐Woon Kim, Myeong‐Chan Cho, Myoung‐Mook Lee, Young‐Bae Park
Journal: European Journal of Heart Failure (2005)
Killed by Care: Making Medicine Safe
Authors: Daniel G. Federman
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Psychosis and ketamine.
Authors: J Davidson, C Brewer
Journal: BMJ (1972)

chest pain radiating to both arms and asso- ciated with sweating.The E.C.G. showed a sinus tachycardia with occasional supraventricular extrasystoles and an inferior in- farct.Serial serum transaminases were raised.The next day she developed a rapid atrial fibrillation for which she was digitalized.However, the dysrhythmia persisted 18 hours and 10 mg verapamil were given intravenously over a period of 20 seconds.Within 10 minutes, her cardiac rate had decreased from 180 per minute to 120 per minute.A tracing at this time showed a
RABBIT POX
Authors: Harry S. N. Greene
Journal: The Journal of Experimental Medicine (1935)

The epidemiological significance of age, race, sex, genetic constitution and physiological status were studied by means of a differential analysis of the mortality data derived from a devastating epidemic of rabbit pox and, with the exception of sex, were found to be factors of the utmost importance in the determination of susceptibility. Young animals were more susceptible than adults and although the most susceptible age varied with the epidemic phase, it corresponded in general with the period of weaning. The influence of physiological status was further indicated by the increased susceptibility incident to lactation. Racial variations in susceptibility were obscured by age factors in young animals, but were of profound importance in the adult population and formed the most significant feature of the analysis. A high degree of conformity was found in the susceptibility of racially related breeds, and this similarity in behavior increased with the proximity of relationship. Moreover, a study of the hybrids obtained from the crossing of pure breeds showed that two separable groups of hereditary factors were concerned in the determination of breed susceptibility, one group consisting of essential racial characters, the other of constitutional factors incorporated in the stock by chance association, and that the final expression of susceptibility or resistance was the result of their combined interaction.
Src-family kinase–dependent disruption of endothelial barrier function by Plasmodium falciparum merozoite proteins
Authors: Mark R. Gillrie, Gowdahalli Krishnegowda, Kristine Lee, Andre G. Buret, Stephen M. Robbins, S. Looareesuwan, D. Channe Gowda, May Ho
Journal: Blood (2007)
Diagnostic Value of Adenosine Conversion of Wide Complex Tachycardia
Authors: Richard Childers
Journal: JAMA Internal Medicine (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Fractionating Heparins and Their Clinical Trial Data—Something for Everyone
Authors: Pranab Das
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal