tbuckley/cabot-search huggingface dataset:
Effects of Nitroglycerin on Erythrocyte Rheology and Oxygen Unloading
Authors: Jian-Ping Bin, Allan Doctor, Jonathan Lindner, Edward M. Hendersen, D. Elizabeth Le, Howard Leong-Poi, Nicholas G. Fisher, Jonathan Christiansen, Sanjiv Kaul
Journal: Circulation (2006)

We hypothesized that nitroglycerin improves O2 delivery to ischemic tissue by altering erythrocyte rheology and O2 unloading through an increase in bioactive nitric oxide (NO) content.Twelve dogs with resting flow-reducing single-vessel stenosis were studied at rest and during intracoronary infusion of nitroglycerin (0.3 to 0.6 microg.kg(-1).min(-1)). Half the dogs also had occlusion of the remote coronary artery to remove any collateral effects. Systemic and coronary hemodynamics, myocardial blood flow (MBF), whole blood viscosity (WBeta), erythrocyte charge (EC) and mobility (EM), regional myocardial O2 delivery and consumption, and tissue O2 pressure (Po2) were measured. No changes in systemic hemodynamics were seen with nitroglycerin. Despite flow-limiting stenosis, MBF increased significantly in the central 25% of the ischemic bed, which was associated with an approximately 19% decrease in WBeta. There was a good correlation (r=0.87) between the two. The decrease in WBeta was associated with a decrease in EC and an increase in EM (r=0.83). The nitroglycerin-induced increase in tissue Po2 was disproportionate to the increase in MBF, indicating enhanced O2 unloading. Erythrocyte S-nitrosothiol content (reflecting mainly S-nitrosohemoglobin) was significantly higher for blood exposed in vitro to 0.1 micromol/L nitroglycerin or the NO donor SNAP, as compared with control (18.9+/-8.8 and 10.5+/-6.5 versus 2.6+/-0.5x10(-5), P<0.05).The augmented MBF in the ischemic microcirculation during nitroglycerin administration occurs in tandem with increased erythrocyte S-nitrosothiol content, EM, and O2 unloading. These additional microvascular mechanisms may contribute to the powerful antiischemic effects of nitroglycerin, especially during low-flow states.
No Loss of Chance of Diabetic Retinopathy Screening by Endocrinologists With a Digital Fundus Camera
Authors: Natacha Germain, Bodgan Galusca, Nilanjana Deb-Joardar, Luc Millot, Pierre Manoli, Gilles Thuret, Philippe Gain, Bruno Estour
Journal: Diabetes Care (2011)

To compare the efficacy of the diabetic retinopathy (DR) screening with digital camera by endocrinologists with that by specialist and resident ophthalmologists in terms of sensitivity, specificity, and level of "loss of chance."In a cross-sectional study, 500 adult diabetic patients (1,000 eyes) underwent three-field retinal photography with a digital fundus camera following pupillary dilatation. Five endocrinologists and two ophthalmology residents underwent 40 h of training on screening and grading of DR and detection of associated retinal findings. A κ test compared the accuracy of endocrinologist and ophthalmology resident screening with that performed by experienced ophthalmologists. Screening efficiency of endocrinologists was evaluated in terms of "loss of chance," i.e., missed diagnoses that required ophthalmologist referrals.The mean weighted κ of DR screening performed by endocronologists was similar to that of ophthalmology residents (0.65 vs. 0.73). Out of 456 DR eyes, both endocrinologists and ophthalmology residents misdiagnosed only stage 1 DR (36 and 14, respectively), which did not require ophthalmologist referral. There were no significant differences between endocrinologists and ophthalmology residents in terms of diabetic maculopathy and incidental findings except for papillary cupping and choroidal lesions, which were not the main purpose of the study or of the training.The endocrinologist with specific training for DR detection using a three-field digital fundus camera with pupillary dilatation can perform a reliable DR screening without any loss of chance for the patients when compared with identical evaluation performed by experienced ophthalmologists.
ALCOHOLISM AND DEGENERATION
Authors: M. D. Sturge, V. Horsley
Journal: BMJ (1910)

To assess the efficacy and safety of <sup>177</sup>Lu-DOTATATE in patients with somatostatin receptor (SSR) positive lung neuroendocrine tumor (NET). <b>Methods:</b> This is a retrospective review of the outcome of patients with typical carcinoid (TC) and atypical carcinoid (AC), treated with <sup>177</sup>Lu-DOTATATE at two ENETS Centres of Excellence. Morphological imaging (RECIST 1.1) and <sup>68</sup>Ga-DOTATATE PET/CT responses were assessed at 3 months after completion of <sup>177</sup>Lu-DOTATATE. Concordance between two response assessment methods was evaluated by Kappa statistics. Progression-free survival (PFS) and overall survival (OS) was estimated by Kaplan-Meier analysis and compared by Log-rank test. Treatment-related adverse events (AEs) were graded based on CTCAE version 5. <b>Results:</b> Of 48 patients (median age, 63 years, 13 female), 43 (90%) had AC and 5 (10%) TC. Almost all patients (47, 98%) were treated due to progression. Majority (40, 83%) received somatostatin analogs and 10 patients (20%) had prior everolimus, chemotherapy or both. All patients had high SSR expression (≥ modified Krenning score 3) on pre-treatment <sup>68</sup>Ga-DOTATATE PET/CT. Patients received a median 4 (range 1-4) cycles of <sup>177</sup>Lu-DOTATATE (33% with concurrent radiosensitizing chemotherapy) to a median cumulative activity of 27GBq (range 6-43GBq). At median follow-up of 42 months, the median PFS and OS were 23 months (95% CI 18-28 months) and 59 months (95% CI 50-not reached [NR]), respectively. Of 40 patients with RECIST-measurable disease and 39 patients with available <sup>68</sup>Ga-DOTATATE PET/CT response categories were: partial response, 20% (95% CI 10-35%) and 44% (95% CI 30-59%); stable disease, 68% (95% CI 52-80%) and 44% (95% CI 30-59%) and progressive disease 12% (95% CI 5-27%) by both, respectively. There was a moderate concordance between response categories by RECIST and <sup>68</sup>Ga-DOTATATE PET/CT, weighted Kappa of 0.51 (95% CI 0.21-0.68). Of patients with stable disease by RECIST, those with partial response on <sup>68</sup>Ga-DOTATATE PET/CT had longer OS compared to those with no response, NR vs 52 months (95% CI 28-64), HR 0.2 (95% CI 0.1-0.6), p 0.001. Most grade 3/4 AEs were reversible and the most common was lymphopenia (14%) with no incidence of myelodysplasia/leukemia. <b>Conclusion:</b> In patients with advanced progressive lung NET and satisfactory SSR expression, <sup>177</sup>Lu-DOTATATE is effective and safe with a high disease control rate and encouraging PFS and OS.
Reply to Berardino De Bari, Filippo Alongi, Stefano Arcangeli's Letter to the Editor re: Cesare Cozzarini, Claudio Fiorino, Chiara Deantoni, et al. Higher-than-expected Severe (Grade 3–4) Late Urinary Toxicity After Postprostatectomy Hypofractionated Radiotherapy: A Single-institution Analysis of 1176 Patients. Eur Urol 2014;66:1024–30
Authors: Cesare Cozzarini, Claudio Fiorino, Alberto Briganti, Francesco Montorsi, Nadia Di Muzio
Journal: European Urology (2014)
Case 54-1961
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. Kibbee
Journal: New England Journal of Medicine (1961)

Presentation of Case First admission. A forty-four-year-old man entered the hospital because of pain in the abdomen. The patient was well until four days previously, when intermittent mild discomfort began in the rectum. On the following day intermittent, crampy pain in the lower abdomen, tenesmus, obstipation and anorexia developed. There had been no nausea, vomiting, melena, loss of weight or change in bowel habits before the onset of the symptoms. He stated that he had swallowed a broken turkey bone five days before admission. Physical examination revealed an obese man in mild distress because of abdominal pain. The lungs and . . .
Correlation Between Anatomy and Electrical Activation in Canine Pulmonary Veins
Authors: Akira Hamabe, Yuji Okuyama, Yasushi Miyauchi, Shengmei Zhou, Hui-Nam Pak, Hrayr S. Karagueuzian, Michael C. Fishbein, Peng-Sheng Chen
Journal: Circulation (2003)

The roles of complex muscle sleeve geometry and fiber orientation in the pulmonary veins (PVs) in wave-front propagation are poorly understood.We mapped the left superior PV (LSPV, n=7) and left inferior PV (LIPV, n=4) of dogs with 420 bipolar electrodes (1-mm resolution) and performed detailed histological examination. In the anterior LSPV-left atrial (LA) junction, myocardial muscle fibers were oriented perpendicular to PV blood flow. A wedge filled with connective tissues led to a complete muscle separation or an abrupt increase in muscle thickness between the PV and LA (0.42+/-0.12 versus 2.0+/-0.31 mm, P<0.01). Distal LSPV pacing resulted in conduction block at the anterior PV-LA junction, with double potentials. In contrast, the posterior LSPV-LA junction showed gradual muscle thickening and a fiber orientation parallel to the blood flow. The maximum PV muscle thickness in the anterior PV-LA junction is thinner than that in the posterior junction (0.83+/-0.15 versus 1.3+/-0.38 mm, P<0.01). Distal LIPV pacing showed multiple PV-LA breakthroughs, with segmental conduction block in the anterior PV-LA junction. The conduction block corresponded to segmental PV-LA muscle disconnection. Complex fiber orientations in the PV muscle sleeves away from the PV-LA junction were responsible for intra-PV conduction delay or block during rapid PV pacing.We conclude that segmental muscle disconnection and differential muscle narrowing at PV-LA junctions and complex fiber orientations within the PV provide robust anatomical bases for conduction disturbance at the PV-LA junction and complex intra-PV conduction patterns.
Fall assessment in older people
Authors: J. C. T. Close, S. R. Lord
Journal: BMJ (2011)

#### Summary points

Falls are common in older people and are the leading cause of injury related admissions to hospital in people of 65 years and over, accounting for about 14% of emergency admissions and 4% of all hospital admissions in this age group.1 A fall may result from acute disease (for example, chest infection), chronic underlying pathology (for example, Parkinson’s disease), or the interaction of a person with their surroundings (for example, tripping on a pavement). Evidence indicates that many falls could be prevented through appropriate assessment and intervention.2 3 4 The terms “fall risk screening” and “fall risk assessment” are sometimes used interchangeably. Screening is a process that primarily aims to identify people at increased risk of falls, whereas assessment aims to identify factors that increase the risk of a fall that can be dealt with by subsequent intervention. In the community setting, a fall risk screen can be used at a population level to identify older people who need a more detailed fall risk assessment and intervention or …
The Bare Facts of General Pathology
Authors: Frances K. Widmann
Journal: JAMA (1975)

A waggish visitor to my office opened this volume looking for nude pictures. He was disappointed. The student looking for rapidly assimilable concepts will also be disappointed. This book resembles lecture notes of a sporadically attentive student in a pathology course taught by diverse lecturers. Some notations are cryptic or liable to misinterpretation by the inexperienced, eg, "Excess hormone may cause some cancers (breast, prostate, endometrial with birth control pills?)." Terms are introduced without definition, eg, under wound healing, "proud flesh"; under etiology of asthma, "anniversary phenomenon"; under syphilitic heart disease, "Zahn-Schminke pockets." Emphasis is bestowed capriciously, eg, seven pages on lysosomes in health and disease, a scant half column on arteriosclerosis. Organizational principles are sometimes baffling, eg, a chapter entitled "Helminths and Diseases of Unknown Etiology," consisting of infectious mononucleosis, sarcoidosis, cat-scratch disease, and assorted wormy infestations not classified as to geography or frequency. Details are either too numerous
SODIUM PERBORATE OINTMENT AND POISON IVY DERMATITIS
Authors: BEDFORD SHELMIRE
Journal: JAMA (1941)

A recent article in Public Health Reports  1 discussed editorially inThe Journal 2 recommends a vanishing cream containing a nonirritating, nonstaining oxidizing agent, such as 10 per cent sodium perborate, as an effective preventive against poison ivy dermatitis. The oxygen liberated by the perborate ointment was said to detoxify the highly allergenic ivy oleoresin. The publicity accorded this new preventive will undoubtedly give many ivy sensitive subjects a false sense of security and result in instances of widespread dermatitis in credulous individuals.  The very stable dermatitis producing fraction of the oleoresin of poison ivy decomposes and becomes inert slowly, if at all, in the presence of large amounts of free oxygen. In my hands this recommended ointment has afforded no greater safeguard against poison ivy dermatitis than has calamine or zinc oxide in vanishing cream, zinc oxide ointment or plain petrolatum, all of which offer only slight mechanical protection.
A new model to monitor the virological efficacy of antiretroviral treatment in resource-poor countries
Authors: Robert Colebunders, Kamya R Moses, John Laurence, Hasan M Shihab, Fred Semitala, Fred Lutwama, Sabrina Bakeera-Kitaka, Lut Lynen, Lisa Spacek, Steven J Reynolds, Thomas C Quinn, Brant Viner, Harriet Mayanja-Kizza
Journal: The Lancet Infectious Diseases (2005)
Increased production or arachidonate metabolites in an occlusion-reperfusion model of canine myocardial infarction
Authors: T. KUZUYA, S. HOSHIDA, M. NISHIDA, Y. KIM, T. KAMADA, M. TADA
Journal: Cardiovascular Research (1987)

To define the role of arachidonate metabolites in evolving ischaemic myocardial damage 10 anaesthetised open chest dogs underwent 90 min occlusion of the left anterior descending coronary artery followed by 5 h reperfusion. Tissue extracts from ischaemic myocardium incubated in vitro were subjected to high pressure liquid chromatography for analysis of lipoxygenase products such as mono hydroxyeicosatetraenoic (HETE) acids and to radioimmunoassay for determining a cyclooxygenase product, thromboxane B2. In ischaemic myocardium the production of 12-HETE (120(35) ng·g−1, mean (SEM)) and thromboxane B2 (18.3(2.4) ng·g−1) was significantly higher than that in normal myocardium (13(2) ng·g−1, p<0.01, and 4.2(0.5) ng·g−1, p<0.001, respectively). 12-HETE production was linearly correlated with thromboxane B2 production in ischaemic myocardium (r=0.718, p<0.02). The increased production of 12-HETE and thromboxane B2 was in proportion to infarct size as measured by a percentage risk area infarcted (r=0.732, p<0.02, and r=0.942, p<0.001, respectively). Similarly, the increase in production of these eicosanoids was related to the degree of leucocyte infiltration in ischaemic myocardium. These results indicate that altered arachidonate metabolism is strongly associated with the progression of ischaemic myocardial damage, suggesting important roles for these eicosanoids, which may be produced by blood corpuscles during the evolution of acute myocardial infarction.
Preoperative estimation of residual volume for WHO grade II glioma resected with intraoperative functional mapping
Authors: Emmanuel Mandonnet, Saad Jbabdi, Luc Taillandier, Damien Galanaud, Habib Benali, Laurent Capelle, Hugues Duffau
Journal: Neuro-Oncology (2006)

Despite the lack of class I evidence, it is widely agreed that surgery can improve the functional and vital prognosis for WHO grade II gliomas when the resection is at least subtotal radiologically, that is, leaving less than 10 cm(3) of visible residual tumor. Because these tumors frequently invade functional areas, the preoperative estimation of the probable residual volume remains challenging. This article presents a probabilistic map of postoperative residues, with the aim of predicting before the decision for surgical intervention whether the resection could be subtotal. We selected 65 patients who underwent surgery with intraoperative functional mapping between 1999 and 2004 for a WHO grade II glioma located in a sensorimotor and/or language area. For each case, the postoperative image was normalized on a standard atlas, and the residual tumor was segmented. A probabilistic map of residues was then computed. The fusion between the map and a preoperative image allowed a preoperative estimation of the expected extent of resection. The map enhances the regions where grade II glioma cannot be resected. The success rate for the preoperative classification of partial versus subtotal resection is 82%. Although both its reliability and accuracy have to be improved, this probabilistic map gives preoperatively an objective estimation of the expected extent of resection for grade II glioma resected under intraoperative functional mapping. This rationale will assist in decisions regarding surgical resection and may thus contribute to the elaboration of a therapeutic consensus for WHO grade II glioma.
Vaginal Spermicides and Congenital Disorders
Authors: Lourdes C. Felarca
Journal: JAMA (1981)

<h3>To the Editor.—</h3> We have reviewed the article by Jick et al. As with another reviewer,<sup>1</sup>we have found a disturbing number of flaws in the methodology. The authors designate as a spermicide "user" any woman who filled a prescription for a spermicide within 600 days of delivery or abortion. This interval is extremely arbitrary; 600 days before abortion is not the same as 600 days before parturition. If any attempt is to be made to compare the results of pregnancies with the results of abortions or to use the results to support a hypothesis on common mechanisms, then an interval based on the time of conception should be chosen. Moreover, no evidence is provided that "users" have been classified correctly. How many of the "nonusers" have used vaginal spermicides in the past (no prescription is required to purchase these products) and how many of the "users" used their
No upregulation of digitalis glycoside receptor (Na,K-ATPase) concentration in human heart left ventricle samples obtained at necropsy after long term digitalisation
Authors: T. A. Schmidt, P. Holm-Nielsen, K. Kjeldsen
Journal: Cardiovascular Research (1991)

Study objective — The aim was to evaluate the hypothesis that digitalis glycosides increase the concentration of their specific receptor (Na,K-ATPase) in human myocardial tissue, thereby possibly reducing the inotropic effect of long term digitalis treatment. Design — Intact samples of left ventricle were obtained at necropsy from patients who had been on long term treatment with digoxin and from patients not previously given digoxin. Digitalis glycoside receptors were quantified using vanadate facilitated 3H-ouabain binding before and after washing samples in buffer containing excess digoxin antibody fragments for 16 h at 30°C. This washing procedure has previously been shown to reduce prior specific digoxin binding in human left ventricle by 95% and to allow subsequent vanadate facilitated complete quantification of 3H-ouabain binding sites. In this context it was performed to reduce occupancy of digitalis glycoside receptors by digoxin, caused by digitalisation before 3H-ouabain binding. Subjects — 11 patients who had been on long term treatment with digoxin and eight who had not previously been given digoxin were studied. Left ventricle samples were obtained at necropsy at around 15 h after death. Measurements and main results — Standard 3H-ouabain binding was 39% less in samples from digitalised than from undigitalised subjects (p<0.001). Washing samples in buffer containing excess digoxin antibody fragments induced an increase in 3H-ouabain binding from 174(SEM 10) to 265(20) pmol·g−1 wet weight (n=11, p<0.001) in samples from digitalised patients. After washing, the digitalis glycoside receptor concentration in left ventricle samples showed a tendency to a lower value (14%, p>0.10) in patients exposed to digoxin compared to left ventricle samples from individuals unexposed to digitalis glycoside treatment. Calculating 3H-ouabain binding relative to dry ventricular muscle weight confirmed the results obtained using wet weight as reference. Conclusions — The results suggest that digoxin treatment in life is associated with a 34% occupancy of digitalis glycoside receptors with digoxin. In the human heart there was no evidence for upregulation of digitalis glycoside receptor concentration due to long term digitalisation. Thus at receptor level there was no evidence for development of tolerance to digoxin therapy. The lower digitalis glycoside receptor concentration in the left ventricle observed in the heart failure patients may support the report of a relationship between Na,K-ATPase concentration as evaluated by 3H-ouabain binding and left ventricular function.
Increased incidence of spontaneous abortion and infertility in women with scleroderma before disease onset: a controlled study.
Authors: A J Silman, C Black
Journal: Annals of the Rheumatic Diseases (1988)

A postal questionnaire was used in a nationwide case control study of women with scleroderma to investigate whether there was an increased rate of spontaneous abortion before the onset of the disease. The results from 155 case control pairs studied showed that the women with scleroderma had twice the rate of spontaneous abortion and three times the rate of fertility problems (no successful pregnancy by the age of 35) of the control women. Previous uncontrolled studies have suggested that established scleroderma is associated with an adverse reproductive history. The results from this investigation suggest that the adverse reproductive history may antedate the clinical diagnosis of scleroderma by many years and may possibly have an aetiological role. Such a hypothesis is consistent with the, as yet unexplained, marked female excess in incidence of the disease, with the peak age of onset occurring shortly after the reproductive period.
Casting and drawing lots: a time honoured way of dealing with uncertainty and ensuring fairness
Authors: W. A Silverman, I. Chalmers
Journal: BMJ (2001)

> The lot causeth disputes to cease, and it decideth between the mighty.
> 
> Proverbs 18:18

What is the ethical basis for offering treatments within a controlled trial? It is either because the doctor and patient do not know which treatment is preferable or because it is the fairest way of deciding who will have a treatment that is in short supply. But what mechanisms should be used to decide who shall receive which treatment and to ensure that the hoped for benefits and unknown risks of inadequately tested treatments are distributed fairly? And how can we ensure that limited supplies of a treatment that may be beneficial are allocated fairly? A solution is found by turning to random allotment, the modern equivalent of one of the oldest practices in human history—the casting or drawing of lots.1

#### Summary points

Casting or drawing of lots has been used for thousands of years to help deal with uncertainty and ensure fairness

It was proposed in the 17th century and adopted in the 19th century for making fair comparisons between alternative medical treatments

It has also been used for the fair distribution of limited resources

It is a fair way of distributing the hoped for benefits and unknown risks of inadequately evaluated forms of health care

Jewish law and the early Christian church outlawed the casting lots for divination—at least by the faithful masses, if not by God's authorities on earth.2 By contrast, casting or drawing lots to assure fairness in allocating duties or rewards has been acceptable for millennia. Human societies have used pebbles, nuts, barleycorn, bones, twigs, yarrow stalks, polished sticks, cards, coins, and dice—the list goes on and …