tbuckley/cabot-search huggingface dataset:
ERASMUS AND HIS DISEASES
Authors: H. N. Cole
Journal: JAMA (1952)

Anyone who has had the pleasure of studying at, or of visiting, Cambridge University, England, will remember Queens College. Queens College, the second royal institution in Cambridge, was established by Margaret of Anjou, queen of Henry VI, in 1448. Andrew Dokett was its first president, and held the office for many years. The college, which is famous for its principal court, gate house, and great gateway, was completed in 1451 and still functions. There are several courts and cloisters, varying in their dates of establishment. All of them are beautiful, as well as ancient, and Pump Court is especially renowned as being the study of the scholar, Erasmus. It is appropriately called Erasmus Tower. In the gallery of the President's lodge there is a high, stiff, uncomfortable chair—Erasmus' chair. Just across the river Cams, there is a walk in the college gardens known as Erasmus' Walk. Erasmus was in residence
NEURITIS OCCURRING AFTER INSECT STINGS
Authors: Norman P. Goldstein
Journal: JAMA (1960)

Although allergic reactions to the stings of bees and wasps have been recorded on a number of occasions, these reactions usually were exaggerations of the common local response, urticaria, or a reaction of an anaphylactic type. Perlman<sup>1</sup>reviewed the literature and reported seven cases of "nearfatal allergic reactions to bee and wasp stings." Less common is the development of neuritis after the sting of an insect. Ross<sup>2</sup>reported that allergy to honeybee stings may result in the clinical picture of peripheral neuritis. Petechiae may be found in the central nervous system when reaction to the sting of an insect is followed by death.<sup>3</sup>Cerebral edema, intraventricular hemorrhage, and meningeal hyperemia also have been reported after death from such a sting.<sup>4</sup>Presumably, similar changes may take place in cranial or peripheral nerves, leading to neuritis, although histological evidence for this supposition is lacking. Because of the scarcity
Cardiac and Systemic Hemodynamic Characteristics of Hypertension and Prehypertension in Adolescents and Young Adults
Authors: Jennifer S. Drukteinis, Mary J. Roman, Richard R. Fabsitz, Elisa T. Lee, Lyle G. Best, Marie Russell, Richard B. Devereux
Journal: Circulation (2007)

Background— The epidemic of overweight is increasing the prevalence of both prehypertension and early-onset hypertension, but few population-based data exist on their impact on cardiac structure and function in adolescents and young adults. Methods and Results— We analyzed clinical characteristics, hemodynamic parameters, and left ventricular structure and function in 1940 participants, 14 to 39 years of age, in the Strong Heart Study. Hypertension occurred in 294 participants (15%), who were more often men (70% versus 30%), older (age, 31±7 versus 25±8 years), and more commonly diabetic (23% versus 4.5%; all P &lt;0.001) than their normotensive counterparts. Prehypertension occurred in 675 (35%) of participants with similar trends in gender, age, and diabetes status. After adjustment for covariates, both hypertensive and prehypertensive participants had higher left ventricular wall thickness (0.83 and 0.78 versus 0.72 cm), left ventricular mass (182 and 161 versus 137 g), and relative wall thickness (0.30 and 0.29 versus 0.28 cm) and 3- and 2-fold-higher prevalences of left ventricular hypertrophy than their normotensive counterparts (all P &lt;0.001). Hypertension and prehypertension also were associated with higher mean pulse pressure/stroke volume index (1.24 and 1.15 versus 1.02 mm Hg/mL · m 2 ) and total peripheral resistance index (3027 and 2805 versus 2566 dynes · s · cm −5 · m 2 ; all P &lt;0.001). Conclusions— In a population with high prevalences of obesity and diabetes, hypertension and prehypertension are associated with increases in both cardiac output and peripheral resistance index. Despite the young age of participants with hypertension and prehypertension, they had prognostically adverse preclinical cardiovascular disease, including left ventricular hypertrophy and evidence of increased arterial stiffness.
Preclinical modeling of endocrine response: a combination therapy approach with the ERβ agonist, diarryl propionitrile and letrozole restores sensitivity to letrozole-resistant breast cancer cells.
Authors: HB Nair, R Jayarajan, SR Saha, P Veerapaneni, B Santhamma, NB Kirma, RP Perla, AK Joseph, DB Evans, AH Brodie, RR Tekmal
Journal: Cancer Research (2009)

Abstract Abstract #17 The majority of breast cancer patients are postmenopausal women with estrogen receptor-positive (ER+) tumors. Approximately 66% of breast carcinomas contain aromatase. Aromatase inhibitors are proving to be more effective than tamoxifen in the treatment of postmenopausal women with ER+ breast cancer. However, the development of resistance to treatment is a concern. The transition of the ER+ tumors from a responsive to unresponsive state is associated with different molecular pathways. We have therefore investigated the properties of resistance that develops in response to the aromatase inhibitor letrozole in the preclinical MCF-7-aromatase xenograft animal model following long-term treatment with letrozole by using the derived letrozole-resistant MCF-7-aromatase LTLTca breast cancer cells. The combination treatment of letrozole and the ERβ agonist diarryl propionitrile (DPN) restored sensitivity to letrozole in the letrozole-resistant LTLTca cells. Studies from our group using this postmenopausal breast cancer preclinical model clearly showed the therapeutic advantage of the ERβ agonist in overcoming unresponsiveness to letrozole. A 67% reduction in tumour size was observed in the group of animals bearing the letrozole-resistant LTLTca tumors that received the combination of letrozole and DPN. A novel delivery method using letrozole-DPN nanoparticles showed enhanced sensitivity (∼80%) to the combination nanoparticles. Letrozole was found to be relatively ineffective in these animals with only a 36% reduction in tumor size with tumors having a mean tumor weight of 0.95g by the end of four weeks of treatment. Biochemical analysis showed a reduction in the tumor aromatase enzyme levels in mice treated with letrozole + DPN when compared to letrozole alone. QRT-PCR as well as protein analysis studies of the letrozole-resistant LTLTca tumors showed a decrease in P27 levels and elevated expression levels of HER-2. Expression levels of cyclin D1 and the ERα to ERb ratio was higher in the untreated letrozole-resistant tumors compared to tumors that responded to the combination therapy. These findings provide further support for the development and testing of novel therapeutic approaches for selective regulation of ER-dependent (ERα and β) actions. Combination treatments involving agents that modulate ERβ activity may provide therapeutic advantage in the treatment, for overcoming resistance to estrogen-ablation and prevention of breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 17.
Abstract 571: Overactive Cdk2 permits polyploidy by overwhelming the tetraploidy checkpoint.
Authors: Stephan Jahn, Patrick Corsino, Mary Law, Brad Davis, Brian Law
Journal: Cancer Research (2013)

Abstract The p53-dependent tetraploidy checkpoint serves to block the proliferation of cells that double their genome without dividing. Oftentimes, cancers will contain a tetraploid sub-population, indicating either an ability to bypass this checkpoint or that the checkpoint is no longer functional. In studying the chromosomal instability of tumor cell lines from mice with mammary expression of a constitutively active Cyclin D1-Cdk2 fusion protein (D1K2), we noticed an increased rate of polyploidization in the presence of the spindle-poison paclitaxel. This was recapitulated in an MCF10A cell line model, and it was discovered that this is due to the inability of the tetraploidy checkpoint to completely stop DNA replication in tetraploid cells with constitutively active Cdk2. Biochemical analysis shows that tetraploid cells expressing D1K2 maintain Rb phosphorylation longer than tetraploid control cells, matching the phenotype seen in cells that have p53 stably knocked down. Further DNA replication, yielding octaploid cells, appears to further intensify the tetraploidy checkpoint, arresting the cells. Due to the fact that approximately 50% of all breast cancers overexpress Cyclin D, these observations raise intriguing questions about the treatment of tumors with overactive Cdk2. While it appears these tetraploid MCF10A cells are unviable, we can not account for other mutations that may exist in vivo and allow the proliferation of a chromosomally unstable tetraploid tumor population. Citation Format: Stephan Jahn, Patrick Corsino, Mary Law, Brad Davis, Brian Law. Overactive Cdk2 permits polyploidy by overwhelming the tetraploidy checkpoint. [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 571. doi:10.1158/1538-7445.AM2013-571
Leptin in obesity
Authors: T. I. Sorensen, S. M Echwald, J.-C. Holm
Journal: BMJ (1996)

Obesity runs in families, mainly due to genetic factors.1 Several different mendelian inherited, monogenic forms of obesity exist in rodents, but they are rare in humans.1 Analysis of the distribution of fatness in families suggests that a few major genes may act on a polygenic and environmental background, but it remains unclear which genes are involved.1

The identification and sequencing of the mouse obese (ob) gene by Friedman's group in 19942 opened important new avenues in obesity research and have already led to overwhelming research activity.3 In homozygous ob/ob mice, the mutation of the ob gene results in increased food intake, reduced energy expenditure, elevated insulin and cortisol levels, and subsequently, in massive obesity and non-insulin dependent diabetes mellitus.2 The ob gene encodes a protein, leptin, which is produced only in fat cells and secreted into the blood. There are two different strains of ob/ob mice: one with a mutation that establishes a stop codon within the ob gene, resulting in the production of a truncated, inactive protein; the other with a mutation that produces no protein at all.2 Administration of leptin corrects the multiple metabolic disturbances.4

The finding of a human homologue of …
Characterization of Low Right Atrial Isthmus as the Slow Conduction Zone and Pharmacological Target in Typical Atrial Flutter
Authors: Ching-Tai Tai, Shih-Ann Chen, Chern-En Chiang, Shih-Huang Lee, Kwo-Chang Ueng, Zu-Chi Wen, Jin-Long Huang, Yi-Jen Chen, Wen-Chung Yu, An-Ning Feng, Chuen-Wang Chiou, Mau-Song Chang
Journal: Circulation (1997)

Background Previous electrophysiological studies in patients with typical atrial flutter suggested that the slow conduction zone might be located in the low right atrial isthmus, which is a path formed by orifice of inferior vena cava, eustachian valve/ridge, coronary sinus ostium, and tricuspid annulus. The conduction characteristics during atrial pacing and responses to antiarrhythmic drugs of this anatomic isthmus were unknown. Methods and Results Forty-four patients, 20 patients with paroxysmal supraventricular tachycardia (group 1) and 24 patients with clinically documented paroxysmal typical atrial flutter (group 2), were studied. A 20-pole halo catheter was situated around the tricuspid annulus. Incremental pacing from the low right atrium and coronary sinus ostium was performed to measure the conduction time and velocity along the isthmus and lateral wall in the baseline state and after intravenous infusion of procainamide or sotalol. In both groups, conduction velocity in the isthmus during incremental pacing was significantly lower than that in the lateral wall before and after infusion of antiarrhythmic drugs. Furthermore, gradual conduction delay with unidirectional block in the isthmus was relevant to initiation of typical atrial flutter. Compared with group 1, group 2 had a lower conduction velocity in the isthmus and shorter right atrial refractory period. Procainamide significantly decreased the conduction velocity, but sotalol did not change it. In contrast, sotalol significantly prolonged the atrial refractory period with a higher extent than procainamide. After infusion of procainamide, the increase of conduction time in the isthmus accounted for 52±19% of the increase in flutter cycle length, and 5 of 12 patients (42%) had spontaneous termination of typical flutter. After infusion of sotalol, typical flutter was induced in only 6 of 12 patients (50%) without significant prolongation of flutter cycle length. Conclusions The low right atrial isthmus with rate-dependent slow conduction properties is critical to initiation of typical human atrial flutter. It may be the potentially pharmacological target of antiarrhythmic drugs in the future.
Persistent Diastolic Dysfunction Late After Valve Replacement in Severe Aortic Regurgitation
Authors: Bruno Villari, Samuel Sossalla, Quirino Ciampi, Bruno Petruzziello, Juraj Turina, Jakob Schneider, Marko Turina, Otto M. Hess
Journal: Circulation (2009)

Regression of left ventricular (LV) hypertrophy with normalization of diastolic function has been reported in patients with aortic stenosis late after aortic valve replacement (AVR). The purpose of the present study was to evaluate the effect of AVR on LV function and structure in chronic aortic regurgitation early and late after AVR.Twenty-six patients were included in the present analysis. Eleven patients with severe aortic regurgitation were studied before, early (21 months) and late (89 months) after AVR through the use of LV biplane angiograms, high-fidelity pressure measurements, and LV endomyocardial biopsies. Fifteen healthy subjects were used as controls. LV systolic function was determined from biplane ejection fraction and midwall fractional shortening. LV diastolic function was calculated from the time constant of LV relaxation, peak filling rates, and myocardial stiffness constant. LV structure was assessed from muscle fiber diameter, interstitial fibrosis, and fibrous content. LV muscle mass decreased significantly by 38% early and 55% late after surgery. Ejection fraction was significantly reduced preoperatively and did not change after AVR (P=NS). LV relaxation was significantly prolonged before surgery (89+/-28 ms) but was normalized late after AVR (42+/-14 ms). Early and late peak filling rates were increased preoperatively but normalized postoperatively. Diastolic stiffness constant was increased before surgery (22+/-6 versus 9+/-3 in control subjects; P=0.0003) and remained elevated early and late after AVR (23+/-4; P=0.002). Muscle fiber diameter decreased significantly after AVR but remained increased at late follow-up. Interstitial fibrosis was increased preoperatively and increased even further early but decreased late after AVR. Fibrosis was positively linearly correlated to myocardial stiffness and inversely correlated to LV ejection fraction.Patients with aortic regurgitation show normalization of macroscopic LV hypertrophy late after AVR, although fiber hypertrophy persists. These changes in LV myocardial structure late after AVR are accompanied by a change in passive elastic properties with persistent diastolic dysfunction.
Alert on Medication Errors
Authors: Rebecca Voelker
Journal: JAMA (1998)

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Increased nonbeneficial care in patients spending their birthday in the ICU
Authors: Elie Azoulay, Maité Garrouste, Dany Goldgran-Toledano, Christophe Adrie, Adeline Max, Aurélien Vesin, Adrien Francais, Jean-Ralph Zahar, Yves Cohen, Bernard Allaouchiche, Benoît Schlemmer, Jean-François Timsit
Journal: Intensive Care Medicine (2012)
Estimation of the Effect of a Preinjection of Tc-99m MDP on Lumbar Spine Bone Mineral Density Determinations
Authors: LEONARD ROSENTHALL
Journal: Clinical Nuclear Medicine (1992)

A 20 mCi dose of Tc-99m MDP administered before dual-photon (x-ray) bone densitometry measurements was shown to reduce the bone mineral density by a mean of 3.9% and the fat content determination by 13.9% in 15 patients.
Cardiovascular responses to dynamic and static effort soon after myocardial infarction. Application to occupational work assessment.
Authors: R F DeBusk, R Valdez, N Houston, W Haskell
Journal: Circulation (1978)

Static and dynamic work involving the arms and the legs was performed by 40 men seven weeks after myocardial infarction. Leg ergometry produced a significantly higher peak work load, systolic blood pressure (BPs), heart rate (HR), and HR X BPs X 10(-2) product (DP) than did arm ergometry: 842 +/- 178 vs 546 +/- 135 kg-m/min, 176 +/- 24 vs 154 +/- 19 mm Hg and 256 +/- 54 vs 219 +/- 48 (SD). Peak heart rates were 145 and 142. Endpoints were primarily muscular and generalized fatigue and dyspnea. Ischemic abnormalities and ventricular ectopy were more frequent with leg ergometry. Sustained forearm lifting elicited higher HR, PBs and DP responses than sustained handgrip contraction: 95 +/- 16 vs 91 +/- 16 beats/min, 162 +/- 18 vs 152 +/- 17 mm Hg and 154 +/- 33 vs 139 +/- 33 (SD). Ischemic ST segment depression and significant ventricuar arrhythmias were infrequent with static effort. Dynamic leg testing is superior to dynamic or static arm testing in assessing the capacity of patients to perform physical work tasks after myocardial infarction.
Does Initial Shunt Type for the Norwood Procedure Affect Echocardiographic Measures of Cardiac Size and Function During Infancy?
Authors: Peter C. Frommelt, Lin T. Guey, L. LuAnn Minich, Majeed Bhat, Tim J. Bradley, Steve D. Colan, Greg Ensing, Jessica Gorentz, Haleh Heydarian, J. Blaine John, Wyman W. Lai, Jami C. Levine, William T. Mahle, Stephen G. Miller, Richard G. Ohye, Gail D. Pearson, Girish S. Shirali, Pierre C. Wong, Meryl S. Cohen
Journal: Circulation (2012)

The Pediatric Heart Network trial comparing outcomes in 549 infants with single right ventricle undergoing a Norwood procedure randomized to modified Blalock-Taussig shunt or right ventricle-pulmonary artery shunt (RVPAS) found better 1-year transplant-free survival in those who received RVPAS. We sought to compare the impact of shunt type on echocardiographic indices of cardiac size and function up to 14 months of age.A core laboratory measured indices of cardiac size and function from protocol exams: early after Norwood procedure (age 22.5 ± 13.4 days), before stage II procedure (age 4.8 ± 1.8 months), and at 14 months (age 14.3 ± 1.2 months). Mean right ventricular ejection fraction was <50% at all intervals for both groups and was higher in the RVPAS group after Norwood procedure (49 ± 7% versus 44 ± 8%; P<0.001) but was similar by 14 months. Tricuspid and neoaortic regurgitation, diastolic function, and pulmonary artery and arch dimensions were similar in the 2 groups at all intervals. Neoaortic annulus area (4.2 ± 1.2 versus 4.9 ± 1.2 cm(2)/m(2)), systolic ejection times (214.0 ± 29.4 versus 231.3 ± 28.6 ms), neoaortic flow (6.2 ± 2.4 versus 9.4 ± 3.4 L/min per square meter), and peak arch velocity (1.9 ± 0.7 versus 2.2 ± 0.7 m/s) were lower at both interstage examinations in the RVPAS compared with the modified Blalock-Taussig shunt group (P<0.001 for all), but all were similar at 14 months.Indices of cardiac size and function after the Norwood procedure are similar for modified Blalock-Taussig shunt and RVPAS by 14 months of age. Interstage differences between shunt types can likely be explained by the physiology created when the shunts are in place rather than by intrinsic differences in cardiac function.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00115934.
132. Increased GFP Gene Delivery to Human Prostate Cancer Cells Using Trancomplementing Adenoviral Vectors
Authors: Elena E. Mitrofanova, Robert C. Unfer, Martha Carvour, Molly Thrall, Jim Higginbotham, Prem Seth, Charles Link
Journal: Molecular Therapy (2006)

Adenoviral vectors are commonly used in cancer research for transgene delivery and expression because of their rapid and significant transgene expression as well as facile production of high viral titers. Unfortunately, relatively inefficient in vivo transgene expression is a characteristic of first generation recombinant adenoviral vectors. Balancing between safety and effectiveness of transgene delivery, many approaches have been used including development of conditionally or limited replicating vectors and utilization of complementing adenoviruses. In this study we exploited two replication defective adenoviral vectors that are able to transcomplement each other to yield limited replication and greater gene delivery.