tbuckley/cabot-search huggingface dataset:
Reperfusion injury in humans: A review of clinical trials on reperfusion injury inhibitory strategies
Authors: M DIRKSEN, G LAARMAN, M SIMOONS, D DUNCKER
Journal: Cardiovascular Research (2007)

The principal therapy in patients with myocardial infarction to limit infarct size is myocardial reperfusion by mechanical or pharmacological intervention. Reperfusion has been proposed to cause myocardial injury beyond that caused by the preceding ischaemia, termed "reperfusion injury" (RI). While the precise mechanism of RI is still incompletely understood, a large number of clinical studies have been performed over the past decade targeting some of the postulated mechanisms of RI. These clinical studies were based on experimental data demonstrating significant myocardial salvage. Nevertheless, clinical benefits were absent or very limited. The purpose of this review is to provide an overview of the various strategies that inhibit RI and to discuss potential mechanisms that may contribute to the discrepancy between the promising pre-clinical data and the rather disappointing results obtained from prospective clinical trials. There are numerous differences between the experimental models and clinical studies, including the fact that experimental studies typically use abrupt occlusion and reperfusion protocols in animals with previously healthy myocardium that apparently do not predict the therapeutic efficacy of novel cardioprotective agents in a clinical setting with pre-existing progressive coronary disease, intermittent coronary occlusion, and relatively late reperfusion. However, discrepancies also exist between experimental studies. Future experimental studies of reperfusion injury should use models that mimic the clinical situation more closely. Furthermore, future large clinical trials should only be performed in cases where the drug under investigation proved to reduce RI in a series of well-designed (possibly multicenter) experimental studies and in clinical trials with predefined subgroups.
TCT-332 A study comparing a paclitaxel drug-eluting balloon with a paclitaxel-eluting stent in diabetic patients with small coronary vessels disease: a sub-study of the the BELLO (Balloon Elution and Late Loss Optimization) Trial
Authors: Francesco Giannini, Antonio Colombo, Charis Costopoulos, Francesco De Felice, Filippo Figini, Azeem Latib, Alberto Menozzi, Antonio Micari, Toru Naganuma, Charbel Naim, Patrizia Presbitero, Gregory A. Sgueglia, Corrado Tamburino
Journal: Journal of the American College of Cardiology (2013)
800. Complete Suppression of CCR5 Expression and Inhibition of HIV-1 Infection by Transfected and Lentiviral Vector Expressed shRNAs
Authors: Joseph S. Anderson, Annaleen Vermeulen, Jon Karpilow, Ramesh Akkina
Journal: Molecular Therapy (2006)

SiRNAs have been shown to be highly potent and sequence specific in targeted gene silencing with great potential for use as therapeutics in combating HIV infection. By targeting the critical coreceptor CCR5, infection can be inhibited at the level of viral entry. The chemokine receptor, CCR5, has been shown to be fully dispensable for normal homeostasis and is, therefore, an excellent target for gene therapy applications. Several reports have so far described the use of CCR5 siRNAs showing varied levels of gene knockdown. In the present study, a new generation of anti-CCR5 siRNAs was designed with the goal of achieving complete silencing. Based on rational target sequence identification criteria, new and more effective CCR5 siRNAs were identified. Complete knockdown of CCR5 expression as determined by FACS and quantitative real time PCR was observed. To achieve stable and constitutive knockdown of CCR5, siRNA coding sequences were cloned individually and in tandem into a lentiviral vector. Vector transduced cells showed similar impressive levels of CCR5 knockdown. When challenged with R5-tropic HIV–1, the siRNA transduced cells exhibited resistance to infection. These results are the first to demonstrate complete constitutive knockdown of CCR5 expression by the use of siRNAs after years of efforts in several laboratories.
THE OPERATIVE TREATMENT OF HALLUX VALGUS AND BUNION
Authors: JOHN D. SINGLEY
Journal: JAMA (1913)

The etiology and pathology of this distressing affection are well known. Though it is objectively trivial, not dangerous to life, its subjects are frequently more grateful for relief than are those on whom some lifesaving operation has been done.  Numerous methods of operation have been devised and practiced, notably those of Barker, Hueter, Riedle, Weir, Fowler and Mayo. In all, except that of Fowler, the approach to the joint is made from the inner side of the foot, which places the scar in a position where it will be subject to pressure from the shoe. Mayo 1 states that this is but a theoretical objection and that practically it causes no trouble.  Fig. 1.  —Fowler's incision for hallux valgus; to be made by dissection, not transfixion, close to outer side of first metatarsal bone; reversal of great toe. Case of moderate degree is shown, requiring removal of but a portion of
Protease-activated receptor 2–dependent fluid secretion from airway submucosal glands by house dust mite extract
Authors: Hyung-Ju Cho, Hyun Jae Lee, Sang Cheol Kim, Kyubo Kim, Yoo Suk Kim, Chang-Hoon Kim, Jeung-Gweon Lee, Joo-Heon Yoon, Jae Young Choi
Journal: Journal of Allergy and Clinical Immunology (2011)
Genes methylated by DNA methyltransferase 3b are similar in mouse intestine and human colon cancer
Authors: Eveline J. Steine, Mathias Ehrich, George W. Bell, Arjun Raj, Seshamma Reddy, Alexander van Oudenaarden, Rudolf Jaenisch, Heinz G. Linhart
Journal: Journal of Clinical Investigation (2011)

Human cancer cells frequently have regions of their DNA hypermethylated, which results in transcriptional silencing of affected genes and promotion of tumor formation. However, it is still unknown whether cancer-associated aberrant DNA methylation is targeted to specific genomic regions, whether this methylation also occurs in noncancerous cells, and whether these epigenetic events are maintained in the absence of the initiating cause. Here we have addressed some of these issues by demonstrating that transgenic expression of DNA methyltransferase 3b (Dnmt3b) in the mouse colon initiates de novo DNA methylation of genes that are similar to genes that become methylated in human colon cancer. This is consistent with the notion that aberrant methylation in cancer may be attributable to targeting of specific sequences by Dnmt3b rather than to random methylation followed by clonal selection. We also showed that Dnmt3b-induced aberrant DNA methylation was maintained in regenerating tissue, even in the absence of continuous Dnmt3b expression. This supports the concept that transient stressors can cause permanent epigenetic changes in somatic stem cells and that these accumulate over the lifetime of an organism in analogy to DNA mutations.
Biomonitoring of 2,4-Dichlorophenoxyacetic Acid Exposure and Dose in Farm Families
Authors: Bruce H. Alexander, Jack S. Mandel, Beth A. Baker, Carol J. Burns, Michael J. Bartels, John F. Acquavella, Christophe Gustin
Journal: Environmental Health Perspectives (2006)

We estimated 2,4-dichlorophenoxyacetic acid (2,4-D) exposure and systemic dose in farm family members following an application of 2,4-D on their farm.
Long hot summer
Authors: G. Dunea
Journal: BMJ (1995)

This year Chicago had its hottest summer in years, as daily temperatures averaged 24.6° and daily highs 30.3°. In July the heat wave claimed the lives of more than 500 people—mostly elderly, debilitated, or afflicted with terminal illnesses. The tobacco manufacturers also took some heat as the American Medical Association urged congress to regulate the industry so that “the thousands who die from smoking each year will not be replaced by new smokers.” Then the Food and Drug Administration, threatened with downsizing or even extinction, made antismoking its new cause and declared nicotine a drug of addiction, which caused house speaker Newt Gingrich to comment that the FDA had lost its mind. Later President Clinton declared teenage smoking a …
Left ventricular diastolic dysfunction limits use of maximum systolic elastance as an index of contractile function.
Authors: M R Zile, G Izzi, W H Gaasch
Journal: Circulation (1991)

We tested the hypothesis that maximum systolic elastance (Emax) fails to detect a decline in left ventricular (LV) contractile function when diastolic dysfunction is present. Canine hearts were studied in an isolated blood-perfused heart apparatus (isovolumic LV); contractile dysfunction was produced by 60 or 90 minutes of global ischemia, followed by 90 minutes of reperfusion. Nine normal hearts underwent 60 minutes of ischemia, and five underwent 90 minutes of ischemia. After the ischemia-reperfusion sequence, developed pressure, pressure-volume area, and myocardial ATP level were significantly less than those at baseline in all 14 hearts. In the group undergoing 60 minutes of ischemia, LV diastolic pressure did not increase, whereas Emax decreased from 5.2 +/- 2.5 to 2.9 +/- 1.4 mm Hg/ml (p less than 0.05). In the group undergoing 90 minutes of ischemia, diastolic pressure increased (from 10 +/- 2 to 37 +/- 20 mm Hg, p less than 0.05), and Emax did not change significantly (from 5.1 +/- 4.3 to 4.3 +/- 2.5 mm Hg/ml). A second series of experiments was performed in 13 hearts with pressure-overload hypertrophy (aortic-band model with echocardiography and catheterization studies before the ischemia-reperfusion protocol). Five had evidence for pump failure, whereas eight remained compensated. After 60 minutes of ischemia and 90 minutes of reperfusion, developed pressure, pressure-volume area, and myocardial ATP level were significantly less than those at baseline in all 13 hearts. In the group with compensated LV hypertrophy, LV diastolic pressure did not change, whereas Emax decreased from 6.9 +/- 3.0 to 3.1 +/- 2.3 mm Hg/ml (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Preparing medical experts for the courtroom
Authors: J Gulleford
Journal: BMJ (1994)

posed arrangements will cause apprehension, to which may be added fears of cumbersome new administrative processes.It is reassuring to find in the report an emphasis on minimising bureaucracy.Researchers are adjusting to research and development commissioning procedures and know that such commissioned work falls within priorities areas.They may fear that under the new arrangements clinical research driven by curiosity may be placed in double jeopardy from grant committees and by priority exclusion.There have been too many instances of medical advances of general importance deriving from such research-the field of cancer genetics is a topical example-for these fears to be ignored.Clear and fair criteria for allocating funds for all categories of research must be developed alongside methods for costing and accounting.Good information on the totality of research taking place in the NHS will be essential, and for this the proposals build on the national project register system already established under the NHS research and development strategy.Hospital trusts with high research profiles should view the proposals for assured funding of research facilities with favour, although their managers may be less enthusiastic that the money will have to be spent according to contract and not simply added to the total hospital budget.However, academics in the associated institutions will have little enthusiasm for another recurrent research assessment as a basis for such awards.Conducting this exercise in parallel with that of the higher education funding coun- cils would seem sensible.Medical schools will have to invest in the administrative capability to contribute to the new NHS arrangements for research.An inevitable conse- quence of the proposals is the death of knock for knock, and the proposals must foreshadow new costing of teaching under the service increment for teaching and research.The proposals that funds for service support as well as
SERUMTHERAPY IN CROUPOUS PNEUMONIA.
Authors: J. C. WILSON
Journal: JAMA (1900)

It is a matter of history that the diplococcus discovered in human saliva by Sternberg in 1880 and shown to produce in rabbits fatal septicemia, was found by Fraenkel a few years later to be almost constant in the rusty sputum of patients suffering from croupous pneumonia and in certain associated lesions. The confirmation of these observations by Weichselbaum led to the designation of this micro-organism as the "pneumococcus of Fraenkel and Weichselbaum." The rapidly following studies of Zaufal, Netter, Weichselbaum and others established the fact that the organism in question is present in the lesion of croupous pneumonia, the accompanying pleurisy, and in such intercurrent conditions as endocarditis, arthritis, middle-ear inflammations, parotitis, meningitis, pericarditis and others and in some cases of bronchopneumonia, orchitis, conjunctivitis and other inflammatory affections not necessarily associated with croupous pneumonia. It is, however, most commonly and closely identified with the last named disease. The inoculation
Cholescintigraphy in the Evaluation of Jaundice
Authors: Shamil J. Morayati
Journal: JAMA (1990)

<h3>To the Editor.—</h3> I read with interest the recent article on the clinical evaluation of jaundice by Dr Frank and members of the Patient Care Committee of the American Gastroenterological Association.<sup>1</sup>The authors reviewed accurately the usefulness of noninvasive studies, including ultrasonography and computed tomographic scan, in the assessment of jaundice. However, the value of cholescintigraphy as an adjunct noninvasive study and in selected cases as the modality of choice in screening patients was overlooked. Ultrasound is poor at detecting common bile duct stones; not all obstructed ducts are dilated and not all dilated ducts are functionally obstructed, especially after cholecystectomy,<sup>2,3</sup>and therefore cholescintigraphy can play a major role in the diagnosis of obstructed jaundice. Its overall accuracy is reported to be about 96% to 97%.<sup>4</sup>Cholescintigraphy has a distinct advantage in patients in whom choledocholithiasis is considered to be the most likely cause (eg, acute
Activation of Vascular Endothelial Growth Factor Receptor-3 in Macrophages Restrains TLR4-NF-κB Signaling and Protects against Endotoxin Shock
Authors: Yanbo Zhang, Yao Lu, Li Ma, Xudong Cao, Jun Xiao, Jiexia Chen, Shaozhuo Jiao, Yunzhen Gao, Chang Liu, Zhaojun Duan, Dangsheng Li, Yulong He, Bin Wei, Hongyan Wang
Journal: Immunity (2014)
THE FAVORABLE PROGNOSIS OF AURICULAR FIBRILLATION
Authors: T. HOMER COFFEN
Journal: JAMA (1923)

Auricular fibrillation in man has generally been considered a result of myocardial damage.1Observations in many cases by many observers make it appear that heart function may not be seriously impaired by this rhythm. Whether this abnormal cardiac rhythm, resulting from profound disturbance in the auricles, throws an added burden on the heart's efficiency, or whether it is one of several unimportant signs of impaired cardiac function, is worthy of consideration. Symptoms and signs of decreased cardiac reserve are found in hearts without this rhythm; etiologic and predisposing factors may be the same as are found in auricular fibrillation, and yet the patients present very similar clinical courses. Some hearts develop this rhythm so insidiously that the patient is but little inconvenienced, even though it becomes permanent. Others, after a period of decompensation coincident with the inception of the new rhythm, are tided over and compensate well for years.
A Critical Appraisal of Pastoral Counseling
Authors: BERNARD L. PACELLA
Journal: American Journal of Psychiatry (1966)

The techniques used by pastoral counselors bear a similarity to those used by the psychiatrist. But if the pastoral counselor undertakes an interpretive or analytic type of therapy, he steps out of his role as pastor in relation to the patient. The author hopes that pastoral counseling will remain more religion-oriented than psychologically oriented, but he also hopes that all clergymen will be offered courses in the seminary aimed at giving them adequate orientation in the fields of mental development and mental health.
Coronary Thrombolysis for the Elderly?
Authors: Jerry H. Gurwitz
Journal: JAMA (1991)

CARDIOVASCULAR disease ranks as the leading cause of disability and death in the elderly. Although those 65 years of age or older constitute only 13% of the US population,<sup>1</sup>80% of all deaths due to acute myocardial infarction (MI) occur in those over the age of 65 years. Of these, 60% occur in patients 75 years of age or older.<sup>2</sup>The in-hospital case-fatality rate for initial acute MI increases from 5% in those less than 55 years of age to 32% in those older than age 75.<sup>3</sup>Patient age at the time of onset of acute MI also affects survival after hospital discharge.<sup>4</sup>For example, results of the Worcester Heart Attack Study indicate a 94% 1-year survival rate among patients with acute MI who are less than 55 years of age and are discharged alive from the hospital, compared with only 77% for those 75 years
Mind-bending infections
Authors: V. K. Viswanathan
Journal: Gut Microbes (2011)

In 1770, Wolfgang von Kempelen presented his famous chess-playing automaton, "The Turk," at the court of Maria Theresa, the Austro-Hungarian empress. The instrument consisted of a life-size, pipe-wielding, turbaned model of a stereotypical Turk seated behind a cabinet table, his right hand resting next to a chess board. "The Turk" played a reasonably good game of chess, its mechanical arms deftly grasping the chessmen and moving them about the board. Opening the doors of the cabinet, one could see a complicated array of gears and cogs cleverly positioned to obfuscate the actual workings of the instrument. "The Turk" subsequently traveled all over Europe and America, and defeated many players, including Napoleon and Ben Franklin. "Perhaps no exhibition of the kind has ever elicited so general attention as the Chess-Player of Maelzel" (Johann Maelzel had purchased "The Turk" from Kempelen's son) wrote Edgar Allen Poe in an essay that speculated about the inner workings of "The Turk." It was finally exposed that the chess moves were actually made by an operator cleverly concealed within the cabinet. "The Turk" was unfortunately lost in a Philadelphia museum fire in 1854.
Mechanisms of Antileukemic Activity of the Novel Bcl-2 Homology Domain-3 Mimetic GX15-070 (Obatoclax)
Authors: Marina Konopleva, Julie Watt, Rooha Contractor, Twee Tsao, David Harris, Zeev Estrov, William Bornmann, Hagop Kantarjian, Jean Viallet, Ismael Samudio, Michael Andreeff
Journal: Cancer Research (2008)

Abstract In this study, we investigated the mechanism of apoptosis induction of obatoclax (GX15-070), a novel Bcl-2 homology domain-3 (BH3) mimetic, in acute myeloid leukemia (AML) cell lines and primary AML samples. Obatoclax inhibited cell growth of HL-60, U937, OCI-AML3, and KG-1 cell lines. Apoptosis induction contributed to the observed antiproliferative effects at concentrations of this agent that mirror its affinity for antiapoptotic Bcl-2 proteins. We show that obatoclax can promote the release of cytochrome c from isolated leukemia cell mitochondria and that apoptosis induced by this agent is preceded by the release of Bak from Mcl-1, liberation of Bim from both Bcl-2 and Mcl-1, and the formation of an active Bak/Bax complex. Notably, apoptosis was diminished, but not fully prevented, in the absence of Bak/Bax or Bim, suggesting that obatoclax has additional targets that contribute to its cytotoxicity. At growth inhibitory doses that did not induce apoptosis or decrease viability, obatoclax induced an S-G2 cell-cycle block. Obatoclax induced apoptosis in AML CD34+ progenitor cells with an average IC50 of 3.59 ± 1.23 μmol/L although clonogenicity was inhibited at concentrations of 75 to 100 nmol/L. Obatoclax synergized with the novel BH3 mimetic ABT-737 to induce apoptosis in OCI-AML3 cells and synergistically induced apoptosis in combination with AraC in leukemic cell lines and in primary AML samples. In conclusion, we show that obatoclax potently induces apoptosis and decreases leukemia cell proliferation and may be used in a novel therapeutic strategy for AML alone and in combination with other targeted agents and chemotherapeutics. [Cancer Res 2008;68(9):3413–20]
General practitioner outpatient referrals: do good doctors refer more patients to hospital?
Authors: G A Reynolds, J G Chitnis, M O Roland
Journal: BMJ (1991)

To investigate the relation between general practitioners' referral rates to individual specialties and the individual areas of expertise of the referring doctors.Data collected on referral patterns in one group practice over nine months.General practice in suburban Birmingham consisting of five partners and a trainee.In 395 referrals there were large differences in referral patterns among partners for otorhinolaryngology, ophthalmology, general surgery, and dermatology. The doctors with particular expertise in otorhinolaryngology and ophthalmology had high referral rates to those specialties, and these differences persisted after allowing for case mix.A high referral rate does not necessarily imply a high level of inappropriate referral.
Impaired Intestinal Absorption of Biotin in Juvenile Multiple Carboxylase Deficiency
Authors: Jess G. Thoene, Rosemary Lemons, Herman Baker
Journal: New England Journal of Medicine (1983)

THE syndrome of biotin-responsive multiple carboxylase deficiency has two relatively distinct phenotypes: a neonatal form, with the onset of life-threatening lactic acidosis, seizures, and erythematous rash occurring in the first weeks of life,1 and a juvenile form, with later onset of acute symptoms of ataxia, alopecia, and keratoconjunctivitis, in addition to seizures and lactic acidosis.2 , 3 Both forms are characterized by an elevation in metabolites proximal to the three biotin-dependent carboxylase reactions, and both show a dramatic response to the administration of pharmacologic doses of biotin. One patient with the neonatal form had deficient activity of biotin holocarboxylase synthetase,4 the enzyme . . .
Respiratory Difficulties at Birth
Authors: R. J. K. Brown
Journal: BMJ (1959)

NORADRENALINE-SECRETING NEUROBLASTOMATA B.n, blastoma and bone metastases may occur.The exact mode of action of vitamin B12 in this condition is not understood.Summary Three cases of neuroblastoma are described in each of which the unusual power of catecholamine secretion gave rise to a clinical picture resembling phaeochromocytoma.From the evidence presented it appears that tissues other than chromaffin are capable of catecholamine secretion.We are of the opinion that neuroblastoma with high catecholamine secretion will prove to be not as rare as the literature suggests.The three cases bring the total number recorded to five.