tbuckley/cabot-search huggingface dataset:
PRELIMINARY NOTE ON A SIMPLE OPERATION FOR UNCOMPLICATED OBLIQUE INGUINAL HERNIA IN YOUNG ADULTS
Authors: G. L. Chiene
Journal: BMJ (1907)

31389~~~~~~~How to account for the presence of peritoneal diver- ticula in the femoral region is, I admit, a difficulty.For my own part, I favour the explanation offered by Mr.Hamilton Russell, of Melbourne) which is that early in fetal life, when the bud-like processes appear from which the lower limbs are developed, a little pouch from the pleuro-peritoneal cavity Is produced by the branches of the femoral vessels assuming a tortuous course, and so dimpling the peritoneum at this point.In this connexion
765-3 Superoxide Dismutase Reduces Superoxide Anion Levels in Balloon-injured Porcine Coronary Arteries
Authors: William D. Anderson, Steven v. Manoukian, Jian Zhang, Timothy E. Peterson, Gustavo D. Cipolla, J. Jeffrey Marshall, Spencer B. King, David G. Harrison, R. Wayne Alexander, Charles B. Treasure
Journal: Journal of the American College of Cardiology (1995)
P2-purinoceptor activation stimulates phosphoinositide hydrolysis and inhibits accumulation of cAMP in cultured ventricular myocytes.
Authors: M Yamada, Y Hamamori, H Akita, M Yokoyama
Journal: Circulation Research (1992)

Extracellular ATP modulates cardiac contraction through P2-purinoceptors on cardiac myocytes. To elucidate the molecular mechanism of this response, we examined the effects of P2-purinoceptor activation on phosphoinositide (PI) hydrolysis and the cAMP system in cultured ventricular myocytes of fetal mice. In a concentration-dependent manner, ATP stimulated accumulations of [3H]inositol monophosphate, bisphosphate, and trisphosphate with the half-maximum effective concentration of approximately 1 microM in the myocytes labeled with [3H]inositol. The order of efficacy of a series of adenyl compounds for stimulation of PI hydrolysis was adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S), ATP greater than ADP, 5'-adenylylimidodiphosphate (APPNP) greater than alpha,beta-methyleneadenosine 5'-triphosphate (APCPP) greater than beta,gamma-methyleneadenosine 5'-triphosphate, AMP greater than adenosine. On the other hand, 100 microM ATP gamma S inhibited isoproterenol-induced accumulation of cAMP by approximately 70% without decreasing the time to maximal cAMP levels, as measured by radioimmunoassay. This response was also concentration dependent, with a half-maximum inhibitory concentration (IC50) of approximately 1 microM. All of the tested ATP, ADP, and ATP analogues inhibited the cAMP system, and the responses to ATP gamma S, APPNP, and APCPP were insensitive to an A1-purinoceptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine. Pertussis toxin attenuated the ATP-induced PI hydrolysis by no more than 25% at 100 ng/ml but completely suppressed the ATP gamma S-induced inhibition of the cAMP system.(ABSTRACT TRUNCATED AT 250 WORDS)
In the Public Interest
Authors: Theodore Cooper
Journal: New England Journal of Medicine (1979)

IT is widely believed that anything done in the public interest is good for society and good for the individual members of society. When the "anything" involves the health of the people, the belief is rapidly converted to doctrine. Doctrine nowadays means law. It is a mark of our era that our highest value is abiding by man-made law. We believe that we are capable of knowing all things. Therefore, it should not be surprising if our self-evaluation frequently exceeds reality and if our appreciation of the value of our proposals for society proves exaggerated. It is good to have . . .
Significant upregulation of antimicrobial peptides and proteins in lichen sclerosus
Authors: T. Gambichler, M. Skrygan, C. Tigges, S. Kobus, R. Gläser, A. Kreuter
Journal: British Journal of Dermatology (2009)

Background Lichen sclerosus (LS) is a chronic inflammatory T cell-driven sclerotic skin condition in which skin barrier disruption frequently occurs. Inflamed and injured epithelia are a particularly rich source of antimicrobial peptides and proteins (AMPs). Objectives We aimed to investigate for the first time the expression pattern of AMPs in lesions of LS as compared with healthy skin. Methods Twenty-four women with LS as well as 10 healthy women were included in the study. In order to assess the expression of human β-defensin (hBD)-1, hBD-2, hBD-3, psoriasin (S100A7), the cathelicidin LL-37 and RNase 7, real-time reverse transcriptase–polymerase chain reaction and immunohistochemistry were performed on skin specimens obtained from lesional and healthy skin of the genital region, respectively. Results Median hBD-2 mRNA levels observed in LS were significantly higher than in controls (0·15 vs. 0·008; P = 0·0037). Moreover, psoriasin (98·2 vs. 28·1; P = 0·0052) mRNA expression was significantly higher in LS lesions as compared with controls. Significant differences in mRNA expression of hBD-2 and psoriasin were also confirmed by immunohistochemistry. For hBD-1, hBD-3, LL-37 and RNase 7, levels did not differ significantly or were significant only at the gene level but not protein level. Conclusions We have demonstrated that hBD-2 and psoriasin expression levels in lesional skin of patients with LS are significantly increased when compared with healthy controls. Whether this observation simply reflects an innate defence response caused by an increased risk of local infection, or whether our data indicate a pathogenetic role of AMPs in LS, will be addressed in future studies.
Lawyers may seek judicial review of panel reviewing paroxetine
Authors: R. Dobson
Journal: BMJ (2003)

Lawyers acting for more than 4000 people who allege side effects from the antidepressant drug paroxetine (Seroxat) may seek a judicial review over the composition of a review panel set up to look at the drug and other selective serotonin reuptake inhibitors (SSRIs).

The lawyers say they are unhappy that some of the committee members have links with the drugs industry. It has been claimed that some members of the review team, which is drawn from the Committee on Safety of Medicines, have shares in GlaxoSmithKline, the maker of paroxetine ( Guardian 17 March: 1).

The review of the side effects of the SSRIs was announced at the end of last year and came in the wake of reports from patients of severe withdrawal symptoms.

The Department of Health …
Abstract 4484: Uracil DNA glycosylase expression determines human lung cancer cell sensitivity to pemetrexed.
Authors: Lachelle D. Weeks, Pingfu Fu, Lili Liu, Stanton L. Gerson
Journal: Cancer Research (2013)

Abstract Uracil misincorporation into DNA is a consequence of pemetrexed inhibition of thymidylate synthetase (TS). The DNA base excision repair (BER) enzyme, uracil DNA glycosylase (UNG) is the major glycosylase responsible for removal of misincorporated uracil. We previously illustrated hypersensitivity to pemetrexed in UNG-/- human colon cancer cells (DLD1) and proposed that cytotoxic uracil accumulation leads to collapsed replication forks, double strand breaks and cell death. Here, we examined the relationship between cellular capability to remove uracil-DNA and pemetrexed sensitivity in human lung cancer cells. Viral siRNA and shRNA knockdown of UNG enhanced pemetrexed sensitivity in A549 and H1975 cells, respectively. We further evaluated induction of UNG as a mechanism of pemetrexed resistance. Exposure of H1299 cells to step-wise increasing concentrations of pemetrexed established drug resistant sublines: H1299PR-1 and H1299PR-2. Significant induction of UNG protein was observed in both sublines. Importantly, co-treatment with the BER inhibitor, methoxyamine (MX), overcame pemetrexed resistance in H1299PR-1/2 underscoring the utility of BER directed therapeutics to offset acquired pemetrexed resistance. Lastly, differential expression of UNG in cell lines and primary lung cancer tissues was associated with pemetrexed sensitivity. Cell lines derived from squamous and small cell carcinoma, known to be clinically resistant to pemetrexed, had the highest levels of UNG expression in a panel of eight lung cancer cell lines. Analysis of cDNA microarrays derived from primary human lung cancer tissues also indicated high UNG expression in pemetrexed-resistant histological subtypes. Thus, we propose that UNG is a major determinant of pemetrexed sensitivity in human lung cancer. Citation Format: Lachelle D. Weeks, Pingfu Fu, Lili Liu, Stanton L. Gerson. Uracil DNA glycosylase expression determines human lung cancer cell sensitivity to pemetrexed. [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 4484. doi:10.1158/1538-7445.AM2013-4484
Induction of progressive glomerulonephritis by podocyte-specific overexpression of platelet-derived growth factor-D
Authors: Claudia R.C. van Roeyen, Frank Eitner, Peter Boor, Marcus J. Moeller, Ute Raffetseder, Lydia Hanssen, Eva Bücher, Luigi Villa, Miriam C. Banas, Kelly L. Hudkins, Charles E. Alpers, Tammo Ostendorf, Jürgen Floege
Journal: Kidney International (2011)
A Clinical Model to Identify Patients With High-Risk Coronary Artery Disease
Authors: Yelin Yang, Li Chen, Yeung Yam, Stephan Achenbach, Mouaz Al-Mallah, Daniel S. Berman, Matthew J. Budoff, Filippo Cademartiri, Tracy Q. Callister, Hyuk-Jae Chang, Victor Y. Cheng, Kavitha Chinnaiyan, Ricardo Cury, Augustin Delago, Allison Dunning, Gudrun Feuchtner, Martin Hadamitzky, Jörg Hausleiter, Ronald P. Karlsberg, Philipp A. Kaufmann, Yong-Jin Kim, Jonathon Leipsic, Troy LaBounty, Fay Lin, Erica Maffei, Gilbert L. Raff, Leslee J. Shaw, Todd C. Villines, James K. Min, Benjamin J.W. Chow
Journal: JACC. Cardiovascular imaging (2015)
Coronary Arteriography
Authors: Sven Bellman, Howard A. Frank, Peter B. Lambert, David Littmann, John A. Williams
Journal: New England Journal of Medicine (1960)

CURRENT interest in the possibilities of surgical reconstruction of occluded coronary arteries is reflected in efforts to develop safe and reliable methods for coronary arteriography.1 2 3 4 5 To be useful clinically, coronary arteriography must be free from local harmful effects and must so regularly fill all major patent vessels that nonfilling may be taken as evidence of occlusion. Although good coronary arteriograms can be obtained with prevailing technics, they are too often inadequate in quality and completeness of contrast filling to be reliable.2 , 6 Most efforts to improve the diagnostic merit of coronary arteriograms have been directed toward increasing the volume and rate . . .
IMPACT OF INTERVENTIONAL VERSUS CONSERVATIVE APPROACH ON 5-YEAR-MORTALITY OF PATIENTS WITH STABLE ANGINA AND DOCUMENTED CORONARY ARTERY DISEASE IN CLINICAL PRACTICE: RESULTS OF THE STAR-REGISTRY
Authors: Anselm K. Gitt, Uwe Zeymer, Andrea Papp, Ralf Zahn, Jochen Senges
Journal: Journal of the American College of Cardiology (2012)
Head-to-head comparison of the Lyon Schuss and fixed flexion radiographic techniques. Long-term reproducibility in normal knees and sensitivity to change in osteoarthritic knees
Authors: M-P H. Le Graverand, E P Vignon, K D Brandt, S A Mazzuca, M Piperno, R Buck, H C Charles, D J Hunter, C G Jackson, V B. Kraus, T M Link, T J Schnitzer, A Vaz, B Wyman
Journal: Annals of the Rheumatic Diseases (2008)

The Lyon Schuss (LS) and fixed flexion (FF) views of the knee are superior to a conventional standing anteroposterior view in evaluating joint space narrowing (JSN) in osteoarthritis (OA). Both position the knee identically but only the LS aligns the medial tibial plateau (MTP) with the x-ray beam fluoroscopically. The present study provides the first head-to-head comparison of the LS and FF views.At baseline and 12 months, 62 OA and 99 control knees were imaged twice on the same day with LS and FF views. Minimum joint space width (mJSW) was measured by computer and MTP alignment was assessed from the distance between anterior and posterior margins of the MTP (intermargin distance, IMD). Reproducibility of measurements of mJSW and sensitivity to change were evaluated.In normal knees, JSW did not vary over 12 months with either view. In OA knees, 12-month mJSN was 0.22 (0.43) mm with the LS view and -0.01 (0.46) mm with the FF view (p = 0.0002 and p = 0.92, respectively). Mean IMD was only half as large in LS as in FF views (0.9 (0.5) mm vs 1.9 (1.2) mm, p<0.0001).LS and FF radiographs offer similar reproducibility in JSW measurement. However, presumably due to its superiority in aligning the MTP, the LS view is much more sensitive to JSN in OA knees.
Recombinant Interferon Gamma in Condylomata Acuminata
Authors: Gerd Gross
Journal: JAMA (1991)

<h3>To the Editor.</h3> — Recent studies have shown that genital warts can be effectively treated with interferon administered intralesionally.<sup>1-3</sup>This approach is not ideal since untreated lesions do not respond and pain at the injection site may limit the use of this route of administration to treat multiple lesions, which are a common clinical presentation of genital human papillomavirus infection. However, using a systemic approach, a recent international multicenter trial,<sup>4</sup>which used subcutaneous injections of recombinant interferon alfa-2a in daily doses of 3.0 mIU or 9.0 mIU three times weekly for 4 weeks, failed to demonstrate the superiority of any of the two interferon groups over the placebo group (response rates of 34% or 25%, respectively, vs 30%). In contrast, low-dose treatment with 1.5 mIU of recombinant interferon alfa-2a, which was given cyclically (daily therapy for consecutive days followed by a therapy-free interval of 4 weeks), seemed to
Surfactant Proteins-A and -B Are Elevated in Plasma of Patients with Acute Respiratory Failure
Authors: IAN R. DOYLE, ANDREW D. BERSTEN, TERENCE E. NICHOLAS
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Surfactant protein-A (SP-A) leaks into the circulation of patients with acute respiratory distress syndrome (ARDS) or acute cardiogenic pulmonary edema (APE) in a manner inversely related to lung function. Since surfactant protein-B (SP-B) is synthesized as a precursor considerably smaller than alveolar SP-A, we investigated whether it enters the circulation more readily. Reactivities consistent with SP-B proprotein ( ∼ 42 to ∼ 45 kD) and the ∼ 25 kD processing intermediate were detected in plasma. Plasma immunoreactive SP-B levels were significantly higher in ARDS (8,007 ± 1,654 ng/ml [mean ± SEM], n = 22) and APE (3,646 ± 635 ng/ml, n = 10) patients compared with normal subjects (1,685 ± 58 ng/ml, n = 33) and ventilated patients with no cardiorespiratory disease (1,829 ± 184 ng/ml, n = 7). All groups had plasma SP-B/SP-A ratios ∼ 6- to ∼ 8-fold higher than in normal lavage or ARDS tracheal aspirate fluid, consistent with protein sieving. During admission, both plasma SP-B and the SP-B/SP-A ratio were inversely related to blood oxygenation (PaO2 /Fi O2 ) (p < 0.0001 and p < 0.025, n = 260 from 39 patients; Spearman) and static respiratory system compliance ( Δ V/ Δ P) (p < 0.0001 and p < 0.01, n = 168 from 25 patients). We describe in detail three patients and conclude that immunoreactive SP-B enters more readily than SP-A, is cleared acutely, and provides a better indicator of lung trauma.
Isolation of mutant T lymphocytes with defects in capacitative calcium entry
Authors: Andrew T. Serafini, Richard S. Lewis, Neil A. Clipstone, Richard J. Bram, Christopher Fanger, Steve Flering, Leonard A. Herzenberg, Gerald R. Crabtree
Journal: Immunity (1995)

Calcium and calcium-binding proteins play important roles in the signaling cascade leading from the initial engagement of TCRs on T cells to the fully activated state. To undertake a molecular dissection of this cascade, we first isolated a Jurkat T cell line derivative containing the NF-AT promoter element driving transcription of the diphtheria toxin A chain gene (dipA), resulting in rapid cell death. Selecting viable cells that fail to activate NF-AT-dependent transcription, we isolated two independent cell lines possessing defects in capacitative Ca2+ entry. NF-AT-dependent transcription can be restored in these cells by expression of a constitutively active calcineurin, but not overexpression of the Ca2+ regulatory protein CAML, which can normally replace the Ca2+ signal. The defect in these cell lines probably lies between CAML and calcineurin in the T cell activation cascade.
Analogy between Tumor Uptake of Technetium(V)-99m Dimercaptosuccinic Acid (DMSA) and Technetium-99m-MDP
Authors: DENIS A. WULFRANK, KAREL H. SCHELSTRAETE, FRANCIS SMALL, CHARLES J. FALLAIS
Journal: Clinical Nuclear Medicine (1989)

Sixty patients with a variety of malignant tumors were examined with Tc-99m(V) dimercaptosuccinic acid (DMSA) prepared by modification of a commercially available DMSA kit. Significant uptake of Tc-99m(V)-DMSA was observed in a number of tumors, offering additional clinically useful information. In the majority of cases in this study, however, the benefit of the Tc-99m(V)-DMSA image was limited because of low sensitivity. The most striking observation was the similarity between the tumor concentration of Tc-99m(V)-DMSA and the Tc-99m-MDP uptake in the tumor on the regular bone image. Therefore, patients with Tc-99m-MDP uptake in nonosseous tumor sites on the bone scan may be suitable candidates for tumor imaging with Tc-99m(V)-DMSA.
Diacylglycerol kinase alpha enhances hepatocellular carcinoma progression by activation of Ras–Raf–MEK–ERK pathway
Authors: Kazuki Takeishi, Akinobu Taketomi, Ken Shirabe, Takeo Toshima, Takashi Motomura, Toru Ikegami, Tomoharu Yoshizumi, Fumio Sakane, Yoshihiko Maehara
Journal: Journal of Hepatology (2012)
A reconstruction of the duct system and secretory tubules of the human bronchial submucosal gland
Authors: B. Meyrick, J. M. Sturgess, L. Reid
Journal: Thorax (1969)

A graphic reconstruction has been made of a submucosal gland from a normal human main bronchus, revealing a collecting duct not previously described. Ciliated respiratory epithelium dips into the gland opening to line the first part of the duct, the <i>ciliated duct</i>, and then gives way, in the <i>collecting duct</i>, to an epithelium composed of tall, columnar, eosinophilic cells containing numerous large mitochondria. This cell structure suggests that the collecting duct controls ionic and water concentration. From the collecting duct arise secretory tubules lined by mucous cells—<i>mucous tubules</i>. Tubules lined by serous cells—<i>serous tubules</i>—arise from mucous tubules either terminally or laterally.
Laboratories should use serum IgM tests to confirm measles
Authors: L. Ryall, C. Goodbourn, A. Taylor, L. Teare
Journal: BMJ (1996)

receiving the results stressful, even when the results were negative.Testing made them more anxious during their pregnancies than they had been during previous ones (even though one family had been in a Middle Eastern war zone during previous pregnancies).Women need to be well informed before they consent to a potentially traumatic testing pro- cedure.3The importance of counselling, however, resides in what the patient grasps, not in what the doctor thinks that he or she has communicated.In one large study 72% of counselled women knew that matemal blood is taken for the test but 33% were unaware that further tests are offered if the result is positive, 62% did not know that the test was for Down's syndrome, and 68% were unaware that most women with positive results have normal babies.4Can consent be truly informed in these circumstances?The screening process is confusing and stressful.Whether any putative benefit outweighs the extra distress for 700000 women each year is open to question.' Shouldn't our cardinal rule be first do no harm?
The Legal Concept of Wrongful Life
Authors: Jeffrey R. Botkin
Journal: JAMA (1988)

THE LAST several decades have brought dramatic improvements in medicine's ability to predict and diagnose genetic and congenital disease. The first prenatal diagnosis of a chromosome defect occurred as recently as 1967, followed the next year by the successful detection of an inborn error of metabolism. Currently, some 200 metabolic and chromosomal disorders can be diagnosed prenatally, and with the rapid development of powerful DNA probes, it may soon be possible to detect all of the 3000 known single-gene defects in humans. This knowledge affords significant benefits to children, parents, and society, but also confers additional responsibilities on the medical profession. With responsibility comes potential liability, so these medical developments have brought a variety of new legally recognized causes for malpractice action. "Wrongful birth" and "wrongful life" are two new legal concepts that have been developed in the last two decades as a result of prenatal diagnostic capabilities and the
NO or no NO in asthma?
Authors: P. J. Barnes
Journal: Thorax (1996)

Nitric oxide (NO) plays a key role as a vasodilator, neurotransmitter, and inflammatory mediator in the airways and is produced in increased amounts in asthma. It may have beneficial effects on airways function as a bronchodilator and is the neurotransmitter of bronchodilator nerves in human airways. On the other hand, NO may have deleterious effects on the airways as a vasodilator by increasing plasma exudation, and may also amplify the asthmatic inflammatory response. Proinflammatory cytokines and oxidants increase the expression of an inducible form of NO synthase (NOS) in airway epithelial cells in asthma, and this may underlie the increased levels of NO found in exhaled air of asthmatic patients. Inducible NOS is inhibited by glucocorticoids, but selective inhibitors of this enzyme may have therapeutic potential in asthma.
Adiposity of the Heart*, Revisited
Authors: Jonathan M. McGavock, Ronald G. Victor, Roger H. Unger, Lidia S. Szczepaniak
Journal: Annals of Internal Medicine (2006)

Obesity is a major risk factor for heart disease. In the face of obesity's growing prevalence, it is important for physicians to be aware of emerging research of novel mechanisms through which adiposity adversely affects the heart. Conventional wisdom suggests that either hemodynamic (that is, increased cardiac output and hypertension) or metabolic (that is, dyslipidemic) derangements associated with obesity may predispose individuals to coronary artery disease and heart failure. The purpose of this review is to highlight a novel mechanism for heart disease in obesity whereby excessive lipid accumulation within the myocardium is directly cardiotoxic and causes left ventricular remodeling and dilated cardiomyopathy. Studies in animal models of obesity reveal that intracellular accumulation of triglyceride renders organs dysfunctional, which leads to several well-recognized clinical syndromes related to obesity (including type 2 diabetes). In these rodent models, excessive lipid accumulation in the myocardium causes left ventricular hypertrophy and nonischemic, dilated cardiomyopathy. Novel magnetic resonance spectroscopy techniques are now available to quantify intracellular lipid content in the myocardium and various other human tissues, which has made it possible to translate these studies into a clinical setting. By using this technology, we have recently begun to study the role of myocardial steatosis in the development of obesity-specific cardiomyopathy in humans. Recent studies in healthy individuals and patients with heart failure reveal that myocardial lipid content increases with the degree of adiposity and may contribute to the adverse structural and functional cardiac adaptations seen in obese persons. These studies parallel the observations in obese animals and provide evidence that myocardial lipid content may be a biomarker and putative therapeutic target for cardiac disease in obese patients.