tbuckley/cabot-search huggingface dataset:
Kallistatin is a potent new vasodilator.
Authors: J Chao, J N Stallone, Y M Liang, L M Chen, D Z Wang, L Chao
Journal: Journal of Clinical Investigation (1997)

Kallistatin is a serine proteinase inhibitor which binds to tissue kallikrein and inhibits its activity. The aim of this study is to evaluate if kallistatin has a direct effect on the vasculature and on blood pressure homeostasis. We found that an intravenous bolus injection of human kallistatin caused a rapid, potent, and transient reduction of mean arterial blood pressure in anesthetized rats. Infusion of purified kallistatin (0.07-1.42 nmol/kg) into cannulated rat jugular vein produced a 20-85 mmHg reduction of blood pressure in a dose-dependent manner. Hoe 140, a bradykinin B2-receptor antagonist, had no effect on the hypotensive effect of kallistatin yet it abolished the blood pressure-lowering effect of kinin and kallikrein. Relaxation of isolated aortic rings by kallistatin was observed in the presence (ED50 of 3.4 x 10(-9) M) and in the absence of endothelium (ED50 of 10(-9) M). Rat kallikrein-binding protein, but not kinin or kallikrein, induced vascular relaxation of aortic rings. Neither Hoe 140 nor Nomega-nitro--arginine methyl ester, a nitric oxide synthase inhibitor, affected vasorelaxation induced by kallistatin. Kallistatin also caused dose-dependent vasodilation of the renal vasculature in the isolated, perfused rat kidney. Specific kallistatin-binding sites were identified in rat aorta by Scatchard plot analysis with a Kd of 0.25+/-0.07 nM and maximal binding capacity of 47.9+/-10.4 fmol/mg protein (mean+/-SEM, n = 3). These results indicate that kallistatin is a potent vasodilator which may function directly through a vascular smooth muscle mechanism independent of an endothelial bradykinin receptor. This study introduces the potential significance of kallistatin in directly regulating blood pressure to reduce hypertension.
Chronic inflammation, immune escape, and oncogenesis in the liver: A unique neighborhood for novel intersections
Authors: Jimmy K. Stauffer, Anthony J. Scarzello, Qun Jiang, Robert H. Wiltrout
Journal: Hepatology (2012)

Sustained hepatic inflammation, driven by alcohol consumption, nonalcoholic fatty liver disease, and/or chronic viral hepatitis (hepatitis B and C), results in damage to parenchyma, oxidative stress, and compensatory regeneration/proliferation. There is substantial evidence linking these inflammation-associated events with the increased incidence of hepatocellular carcinogenesis. Although acute liver inflammation can play a vital and beneficial role in response to liver damage or acute infection, the effects of chronic liver inflammation, including liver fibrosis and cirrhosis, are sufficient in a fraction of individuals to initiate the process of transformation and the development of hepatocellular carcinoma. This review highlights immune-dependent mechanisms that may be associated with hepatocellular oncogenesis, including critical transformative events/pathways in the context of chronic inflammation and subverted tolerogenesis. (Hepatology 2012)
The association between lichen sclerosus et atrophicus and auto-immune diseases in males is not proven
Authors: N. B. Simpson
Journal: British Journal of Dermatology (1984)

Journal Article The association between lichen sclerosus et atrophicus and auto‐immune diseases in males is not proven Get access N. B. Simpson N. B. Simpson Department of Dermatology, Royal Infirmary, Glasgow G 4 oSF, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 111, Issue 1, 1 July 1984, Pages 121–122, https://doi.org/10.1111/j.1365-2133.1984.tb04027.x Published: 01 July 1984
T Cell–dependent Immune Response in C1q-deficient Mice: Defective Interferon γ Production by Antigen-specific T Cells
Authors: Antony J. Cutler, Marina Botto, Dominic van Essen, Roberta Rivi, Kevin A. Davies, David Gray, Mark J. Walport
Journal: The Journal of Experimental Medicine (1998)

The role of the classical complement pathway in humoral immune responses was investigated in gene-targeted C1q-deficient mice (C1qA−/−). Production of antigen-specific immunoglobulin (Ig)G2a and IgG3 in primary and secondary responses to T cell–dependent antigen was significantly reduced, whereas IgM, IgG1, and IgG2b responses were similar in control and C1qA−/− mice. Despite abnormal humoral responses, B cells from C1qA−/− mice proliferated normally to a number of stimuli in vitro. Immune complex localization to follicular dendritic cells within splenic follicles was lacking in C1qA−/− mice. The precursor frequency of antigen-specific T cells was similar in C1qA−/− and wild-type mice. However, analysis of cytokine production by primed T cells in response to keyhole limpet hemocyanin revealed a significant reduction in interferon-γ production in C1qA−/− mice compared with control mice, whereas interleukin 4 secretion was equivalent. These data suggest that the classical pathway of complement may influence the cytokine profile of antigen-specific T lymphocytes and the subsequent immune response.
Physicians and Family Caregivers: A Model for Partnership
Authors: Lisa Fredman, Mel P. Daly
Journal: JAMA (1993)

<h3>To the Editor.</h3> —The Council Report<sup>1</sup>on primary care physicians and family caregivers addressed two important aspects of the interaction between primary care physicians and caregivers: the detection of stress among caregivers and suggestions made by physicians to reduce stress. However, we were concerned that the proposed recommendations were more theoretical than practical. We offer several pragmatic applications of the model proposed in the report. The stability of the patient-caregiver unit is, indeed, critical to maintaining frail elderly persons in the community. However, the patient-caregiver unit might be difficult to identify. Some caregivers may be identified when they bring the elderly person to the physician's office,<sup>2</sup>but others may be overlooked. Physicians need to ask patients whether they have sole or shared responsibility for aging parents or other relatives, and what that responsibility entails. To evaluate the stability of the patient-caregiver unit, we have developed an instrument (the
Hernia of Morgagni
Authors: F. Paris, V. Tarazona, M. Casillas, E. Blasco, A. Canto, J. Pastor, A. Acosta
Journal: Thorax (1973)

<b>París, F., Tarazona, V., Casillas, M., Blasco, E., Cantó, A., Pastor, J., and Acosta, A. (1973).</b><i>Thorax</i>, <b>28</b>, 631-636. <b>Hernia of Morgagni.</b> Nine patients with Margagni9s hernia of the diaphragm are reported, seven of whom have been operated on. Four patients had gastrointestinal symptoms, two respiratory symptoms, and one retrosternal pain; the other two were asymptomatic. In the first case the diagnosis was made at the time of thoracotomy, in the other eight it was suggested by radiological studies. The standard midline epigastric incision was used for repair in four cases and thoracotomy in two; the last patient was operated on through a preperitoneal subxiphoid route. This route has the advantage of not requiring a wide incision of peritoneum.
Host-Directed and Immune-Based Therapies for Human Immunodeficiency Virus Infection
Authors: Michael M. Lederman
Journal: Annals of Internal Medicine (1995)

This essay reviews the rationale underlying host-directed or immune-based therapeutic strategies for human immunodeficiency virus (HIV) infection and its complications. These approaches have seen only limited trial in the past 10 years, but as more is learned about the immunopathogenesis of HIV disease and as the limitations of virus-directed therapies become more apparent, the need to pursue other therapeutic avenues has become increasingly important. Moreover, properly designed trials of host-directed and immune-based therapies can provide key insights into the pathogenesis of HIV disease that may be otherwise unattainable through in vitro studies.
Pulled elbow: a study of 100 patients.
Authors: C M Illingworth
Journal: BMJ (1975)

Pulled elbow is a common condition but may not be recognized by practitioners unaware of its existence. Most of a series of 100 children with this condition were aged 1 or 2 years, and none were over 6 years. An important precipitating factor was the normal recalcitrance of the 1-3 age group. The three children who were over 5 years had all had earlier episodes which may have stretched the annular ligament. The wrist was the most common site of pain after the elbow. A single manipulation was successful in 96 cases but multiple manipulations may be needed.
Photodynamic Therapy Triggers Cytotoxic Drug Retained to Greater Degree by Cancer Cells
Authors: Eric Bernicker
Journal: JAMA (1989)

RESEARCHERS ARE hoping that the triple threat of light, oxygen, and light-sensitive drugs will usher in a new age in cancer treatment. The new weapon, called photodynamic therapy, uses laser light to activate a cytotoxic drug selectively in tumor cells. The drugs involved, hematoporphyrin and its more potent derivative, dihematoporphyrin ether (DHE, Photofrin) (Quadra Logic Technologies, Vancouver, Canada), have been known to be light activated since early in this century. But it was not until the 1970s that the first systemic use of photodynamic therapy was pioneered by Thomas Dougherty, PhD, and his group at Roswell Park Memorial Institute, the New York State facility in Buffalo. The drug enters both normal and malignant cells. However, it is retained to a greater degree by neoplastic cells. Thus, 48 to 72 hours after administration, there is a gradient between the normal cells and the tumor. Photodynamic therapy seeks to exploit this. The
Low concentrations of angiotensin II unmask vasoconstrictory 2-adrenoceptors in isolated perfused kidneys of spontaneously hypertensive rats
Authors: C. Bohmann, W. Rist, P. Schollmeyer, L. C. Rump
Journal: Cardiovascular Research (1995)

The aim of the present study was to evaluate the role of vascular alpha 1- and alpha 2-adrenoceptors in kidneys of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY).SHR and WKY kidneys (12-14 weeks) were isolated and perfused with Krebs-Henseleit solution. Concentration-response curves for the alpha 1-adrenoceptor agonist methoxamine and the alpha 2-adrenoceptor agonist UK 14304 were constructed alone and in the presence of the alpha 1-adrenoceptor antagonist prazosin, the alpha 2-adrenoceptor antagonist idazoxan and exogenous angiotensin II.Methoxamine induced a maximal pressor response of 247 +/- 9 mmHg with an EC50 of 1.3 +/- 0.1 microM in SHR and of 193 +/- 4 mmHg with an EC50 of 1.1 +/- 0.1 microM in WKY. The concentration-response curve for methoxamine was shifted to the right by prazosin with a pA2 value of 9.29 (SHR) and 9.26 (WKY) and by idazoxan with a pA2 value of 6.45 (SHR) and 6.33 (WKY). UK 14304 induced a maximal pressor response of 41 +/- 12 mmHg in SHR and of 37 +/- 8 mmHg in WKY. Angiotensin II (0.1 nM) did not significantly alter pressor responses to methoxamine but caused a marked shift to the left of the concentration-response curve for UK 14304. UK 14304 then induced a maximal pressor response of 92 +/- 13 mmHg with an EC50 of 0.07 +/- 0.01 microM in SHR and of 78 +/- 14 mmHg with an EC50 of 0.14 +/- 0.01 microM in WKY. In the presence of angiotensin II (0.1 nM) the concentration-response curve for UK 14304 was shifted to the right by prazosin with a pKB of 6.36 (SHR) and 6.33 (WKY) and by idazoxan with a pKB of 7.68 (SHR) and 7.65 (WKY).The results demonstrate a predominant role of vasoconstrictory alpha 1-adrenoceptors over alpha 2-adrenoceptors in SHR and WKY isolated kidneys. Low physiological concentrations of angiotensin II unmask functional vascular alpha 2-adrenoceptors which are slightly more sensitive in SHR than in WKY kidneys.
Gastro-oesophageal reflux disease and Helicobacter pylori: an intricate relation
Authors: D McNamara, C O'Morain
Journal: Gut (1999)

Heartburn is a common symptom affecting 21-44% of the adult population on a monthly basis. Oesophagitis is less common, affecting 2% of individuals. Epidemiological studies have shown that patients with gastro-oesophageal reflux disease (GORD) have similar incidence rates of Helicobacter pylori infection as do controls. Some groups have reported that there is a lower incidence, deducing that infection does not cause, and in some way confers protection against GORD. Additional supportive evidence is available from reports of GORD development following successful H pylori eradication. The mechanisms involved are complicated. Individuals with H pylori induced pangastritis and subsequent hypochlorhydria may be protected whereas those with an antral predominant gastritis, as in duodenal ulcer disease, with an increased acid output may be prone to development of GORD. Recent evidence has linked H pylori infection with the development of inflammation of the gastric cardia---carditis. Reports are available which show that carditis is a frequent finding in patients with GORD. The incidence of both cardia and oesophageal carcinoma is increasing. The relation between GORD, carditis, intestinal metaplasia, and cardia carcinoma is unclear. Intestinal metaplasia may result from multifocal atrophic gastritis, linked to H pylori infection or from GORD and the development of Barrett's oesophagus. Long term follow up studies will be required to assess the malignant potential of these histological entities and whether or not H pylori infection has an aetiological role.
Megaloblastic Anemia Associated with Chronic Ingestion of an Analgesic
Authors: Jack O. Williams, Charles E. Mengel, Louis W. Sullivan, Anwarul S. Haq
Journal: New England Journal of Medicine (1969)

DRUGS may induce anemia by a variety of mechanisms,1 including blood loss, hemolysis, bone-marrow suppression and megaloblastic arrest. Anticonvulsants2 such as diphenylhydantoin,3 the barbiturates4 and primidone,5 alone or in combination, have been reported to cause megaloblastic anemia although this therapeutic complication is not frequent.6 In the case reported below, a severe anemia with megaloblastic arrest of the bone marrow appeared to be associated with the chronic ingestion of an analgesic containing aspirin, salicylamide and caffeine (Stanback).Case ReportE.W., a 57-year-old housewife, was admitted to the Ohio State University Hospital on 3 occasions in 1967 because of anemia. During the . . .
The Effect of Radiotherapy to the Thorax on Pulmonary Function.
Authors: C. Emirgil
Journal: Annals of Internal Medicine (1962)

s1 April 1962The Effect of Radiotherapy to the Thorax on Pulmonary Function.C. Emirgil, M.D., H. O. Heinemann, M.D.C. Emirgil, M.D.Search for more papers by this author, H. O. Heinemann, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-56-4-696_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPatients afflicted with various types of neoplastic disease not infrequently succumb to respiratory insufficiency. The nature of the pulmonary pathology varies, and the underlying physiological derangements which lead to respiratory death are usually complex. One of the variables contributing to the development of respiratory insufficiency is radiotherapy to the chest. To evaluate the effect of radiation on pulmonary function, 15 patients free of cardiac and pulmonary disease, who were receiving radiotherapy for carcinoma of the breast or lung, were studied. Lung volumes, distribution of inspired air, arterial blood gases, diffusing capacity of the lung, and mechanics of breathing were measured... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y. (CI) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1962Volume 56, Issue 4Page: 696-696KeywordsBreathingHeart diseasesLung and intrathoracic tumorsLungsPulmonary diseasesPulmonary functionRespiratory failureRespiratory physiologyThoraxVentilators Issue Published: 1 April 1962 PDF downloadLoading ...
Acetaminophen Hepatotoxicity-Reply
Authors: James R. O'Dell
Journal: JAMA (1986)

<h3>In Reply.—</h3> We appreciate the comments of Hall and colleagues. We believe our patient had superimposed acetaminophen hepatotoxicity because of the laboratory features and charac teristic centrilobular injury. She was taking no other hepatotoxic drugs (except alcohol) and had not knowingly been exposed to any other toxins. We agree that chronic liver disease alone does not predispose patients to hepatotoxicity from therapeutic acetaminophen use. She did not have any histologic or clinical evidence of cirrhosis. Rather, this case report describes an alcohol-abusing patient who developed centrilobular fibrosis while ingesting what she perceived to be a routine dose of acetaminophen—two extra-strength acetaminophen capsules every four hours. Potentiation of acetaminophen toxicity in chronic alcoholics receiving small doses of acetaminophen has been previously described.<sup>1,2</sup>Fasting also enhances experimental acetaminophen hepatotoxicity<sup>3</sup>and her dietary intake may have been poor. Other enzyme-inducing agents such as phenobarbital have also been shown to potentiate acetaminophen
1169-154 Steady state free precession perfusion allows visual assessment for the clinical diagnosis of ischemia
Authors: Nico Merkle, Thorsten Nusser, Jochen Wöhrle, Hans A Kestler, Bernhard Schnackenburg, Martin Höher, Matthias Kochs, Vinzenz Hombach, Olaf Grebe
Journal: Journal of the American College of Cardiology (2004)
Toxicity of Levamisole and 5-Fluorouracil in Human Colon Carcinoma Cells
Authors: J. L Grem, C. J. Allegra
Journal: JNCI Journal of the National Cancer Institute (1989)

The combination of 5-fluorouracil (5-FU) with the immunomodulator levamisole (Lev) has been clinically tested in patients with metastatic colorectal carcinoma and as adjuvant therapy following primary tumor surgery. In some studies in advanced disease, the addition of Lev to 5-FU improved the median duration of response; in the adjuvant setting, the combination was associated with improvement in the disease-free survival. We studied whether Lev was directly toxic to three human colorectal carcinoma cell lines (HCT 116, SNU-C4, and NCI-H630). We also evaluated the toxicity of Lev in combination with 5-FU in these three cell lines. Lev inhibited the growth of all three colorectal cell lines, but only at concentrations two logs above that achieved with a standard 150-mg oral dose of Lev. In cell growth studies, 500 and 1,000 microM Lev increased the toxicity of 5-FU in HCT 116 cells in an additive fashion. In clonogenic assays, continuous exposure to 10 or 100 microM Lev was minimally toxic and did not enhance the lethality associated with a 24-hour exposure to 5-FU in any of the cell lines. Lev alone at 1,000 microM decreased colony formation by 45% in HCT 116 cells. A combination of 1,000 microM Lev with 10 microM 5-FU resulted in a decrease in HCT 116 colony formation from 54% to 6% of control levels. Continuous exposure of NCI-H630 cells to 500 microM Lev decreased colony formation to 76.5% of control levels; when Lev was combined with 50 microM 5-FU, colony formation was decreased from 59.5% to 27.5% of control levels. We conclude that at concentrations achievable with conventional doses of Lev, there was no evidence of direct toxicity in these colorectal cell lines. Furthermore, an additive interaction with 5-FU was evident only at suprapharmacologic doses of Lev.
Renal denervation in heart failure with normal left ventricular ejection fraction. Rationale and design of the DIASTOLE (DenervatIon of the renAl Sympathetic nerves in hearT failure with nOrmal Lv Ejection fraction) trial
Authors: Willemien L. Verloop, Martine M.A. Beeftink, Alex Nap, Michiel L. Bots, Birgitta K. Velthuis, Yolande E. Appelman, Maarten‐Jan Cramer, Willem R.P. Agema, Asbjorn M. Scholtens, Pieter A. Doevendans, Cor P. Allaart, Michiel Voskuil
Journal: European Journal of Heart Failure (2013)
Vasodilator therapy in chronic asymptomatic aortic regurgitation: Enalapril versus hydralazine therapy
Authors: Mike Lin, Hung-Ting Chiang, Shoa-Lin Lin, Mau-Song Chang, Benjamin N. Chiang, Hsien-Wen Kuo, Melvin D. Cheitlin
Journal: Journal of the American College of Cardiology (1994)
Financing Medical Education -- A Universal “Berry Plan” for Medical Students
Authors: R G Petersdorf
Journal: New England Journal of Medicine (1993)

In the wake of the Korean War, a controversy developed over the needs of the armed services for medical officers and the needs of hospitals for interns and residents. To satisfy both parties and be fair to the young men who were subject to selective service, a plan was devised that permitted young physicians to choose among three options: entering the armed services immediately after internship and returning to their residencies after service; entering the armed services two years after medical school and completing their residencies after service; and entering the service after the completion of residency training. This plan, . . .
Third-Line Sorafenib After Sequential Therapy With Sunitinib and mTOR Inhibitors in Metastatic Renal Cell Carcinoma
Authors: Giuseppe Di Lorenzo, Carlo Buonerba, Piera Federico, Pasquale Rescigno, Michele Milella, Cinzia Ortega, Michele Aieta, Carmine D'Aniello, Nicola Longo, Alessandra Felici, Enzo Maria Ruggeri, Giovannella Palmieri, Ciro Imbimbo, Massimo Aglietta, Sabino De Placido, Vincenzo Mirone
Journal: European Urology (2010)
"How can I avoid being sued?"
Authors: Daniel K Sokol
Journal: BMJ (2011)

Common sense is the key



“Doctors don’t care much about ethics,” an unusually frank junior doctor told me one day. “What they care about is law: they don’t want to get sued.” As an ethicist and, like all healthy people, a patient in waiting, I believe strongly that doctors should provide medical care to a high ethical standard.

Yet, as a lawyer, I am aware that many ethical violations have no consequence in law. A healthcare professional may wander through the hospital, exuding rudeness and disdain from every pore, leaving a trail of anxious patients and relatives in his wake, without any legal repercussions. A breach of the duty of care is, in itself, not enough. There must be an injury resulting from that breach; and, in the eyes of the law, grief, anger, and upset are not injuries.

The law, however, does try to keep up with ethics. In Chester v Afshar,1 a neurosurgeon failed to inform the patient of a 1-2% chance of developing cauda equina syndrome from spinal surgery. Sadly, despite being operated on competently, she developed the condition and sued …