tbuckley/cabot-search huggingface dataset:
Comment: The Mantle Failure: The Transdiaphragmatic Extension
Authors: Philip Rubin
Journal: JAMA (1973)

The major impetus for the development of new techniques of treatment is the failure of an existing technique. In the early sixties, the introduction of pedal lymphangiography to exclude infradiaphragmatic nodes promised precise definition of localized stage I and II Hodgkin's disease. The use of megavoltage irradiation through a shaped mantle field to treat the nodal disease and adjacent sites above the diaphragm promised cure, since adequate tumoricidal doses could be delivered. The "mantle technique" controlled approximately 50% to 60% of all such patients, as documented in numerous series.<sup>58</sup>The pattern of failure was consistent; the vast majority of patients had a transdiaphragmatic extension of disease, most often involving the para-aortic lymph nodes or the spleen. The transdiaphragmatic extension to the para-aortic lymph node region has been a central focus of discussion. Its subsequent appearance despite negative lymphangiograms has led to speculations about its development. The most controverted concept
An Address on MATERNAL MORTALITY FROM PUERPERAL SEPSIS: AN ANALYSIS OF THE FACTORS OF CONTAGION, TRAUMA, AND AUTO-INFECTION
Authors: J. Young
Journal: BMJ (1928)

IT is uinnecessary in these days to emphasize the tragic im- portance to the community of the large mortality amongst young women which is incurred yearly through child- bearing and childbirth.In these islands the maternal dteath rate is about 4,000 each year; between 1911 and 1926 inclusive there were 66,421 deaths from these causes in England and Wales.Septic infection is by far the most important single cause.According to the official figures for 1926 the total maternal mortality for England and Wales was 5.14, and the sepsis mortality 1.60, per 1,000 live births.This loss bv death, however, is in some ways not the gravest consequence of child-bearing, for we have come to iealize that, for each mother so lost, there are many more Wliose health is in varying degrees chronically undermined by the d-amage they have stustained in childbed.Infection and mechanical damage thus acquired are amongst the main causes of the frequent chronic ill health which dates from childbirth.We can assess within accurate limits the loss by death, but of the incidence of persisting invalidism of child-bearing origin we have no exact knowledge.-We_know with certainty, however, that many of the common gyn-aecological disorders, the uterine haemorrhages, the leucorrhoeas, the pelvic pains, the displacements, etc., and many general disturbances, debility, indigestion, neur- asthenia, rhieumiiatism, etc., are to be traced to the lesions of childbirth.It is probably not an over-statement to sav that abouit 60 per cent. of hospital g-naecology is a legacy from vitiated child-bearing, and of this a very large part falls into the category of infection.Septic inflammationi of the genital canal during labour or in the pluerperiulm may, as a useful basis for analysis, be considered as falling into one or other of three clinical types according as it is caused by (1) contagion, (2) trauma, or
Obama tries to defuse anger over healthcare reforms
Authors: J. H. Tanne
Journal: BMJ (2009)

The US president, Barack Obama, spent last week trying to quell furious protests over his proposed healthcare reforms. This included speaking at town hall meetings in the western states of Montana and Colorado.

The president and his secretary of health and human services, Kathleen Sebelius, are apparently backing down from insisting on a “public option” plan that would compete with private, profit making health insurance plans. Instead a non-profit cooperative organisation offering plans might be on the cards.

The president set out the benefits of the reforms in a New York Times article in which he said that the current system often worked better for health insurance companies than for patients (www.nytimes.com, 16 Aug, “Why we need health care reform”).

About 46 million Americans have no health insurance. But about 80% do, …
Levels of erythropoietin in patients with the anemias of chronic diseases and liver failure
Authors: S. F. Wallner, J. E. Kurnick, R. M. Vautrin, M. J. White, R. G. Chapman, H. P. Ward
Journal: American Journal of Hematology (1977)

Abstract Two mechanisms are felt to be responsible for the production of anemia in patients with chronic diseases. The first is failure to produce adequate amounts of erythropoietin (EP), and the second is failure to deliver iron to the bone marrow in amounts sufficient to support normal erythropoiesis. In order to evaluate these hypotheses we studied urine and serum EP levels and levels of 2,3‐diphosphoglycerate in normal subjects, in patients with the anemia of chronic diseases, in patients with chronic liver disease, and in patients with a variety of other anemias. Based on the results, we propose first that insufficient production of EP is one of the major mechanisms responsible for anemia in patients with chronic diseases. Second, insufficient production of EP is, in part, responsible for anemia seen in patients with chronic liver disease. Third, serum and urine EP levels decrease with aging, and this correlates with the fall of hemoglobin levels seen in older normal subjects.
A Low Recurrence Rate is Possible With a Combination of Surgery and Radiosynovectomy for Diffuse Pigmented Villonodular Synovitis of the Knee
Authors: Gokhan Koca, Hakan Ozsoy, Hasan Ikbal Atilgan, Sinem Ozyurt, Koray Demirel, Hasan Yiğit, Meliha Korkmaz, Aylin Baskin, Abdurahman Sakaogullari, Mustafa Ozdemir
Journal: Clinical Nuclear Medicine (2013)

Diffuse pigmented villonodular synovitis (DPVNS) is an uncommon proliferative disease. After only surgery, recurrence rates are high. This study presents the efficacy of combined surgical and adjuvant radiosynovectomy (RS) in the treatment of DPVNS.Between September 2006 and September 2012, 15 knee joints of 15 patients (10 female and 5 male) with histopathological DPVNS diagnosis with mean age 27 ± 12 years underwent surgery. At mean 14.4 ± 18 weeks postoperatively, RS was applied using 5 mCi (90)Y citrate colloid. Three-phase bone scintigraphy and contrast-enhanced MRI were used to evaluate residual and recurrent tumorous tissues in the joint.Mean follow-up was 48 ± 22 months. Blood flow and blood pool images showed that 2 patients had marked, 4 had moderate, 6 had mild, and 3 had no uptake. Late static images showed 5 had marked, 10 had moderate (99m)Tc-HDP uptake in the related joint. MRI examination indicated that there was no progression in any of the patients. The disease was determined to be stable in 2, regressed in 9, and totally cured in 4 cases. Bremsstrahlung imaging indicated an even distribution of radionuclide in all the knee joints. There was no evidence of leakage of radioactivity in the total body scans. There was significant improvement in Lysholm knee scores after treatment.Adjuvant yttrium-90 radiosynovectomy after surgical excision in the treatment of DPVNS is a reliable and efficient treatment method with successful clinical results. RS treatment can be considered for cases with DPVNS.
First-Line Therapy for Adult Patients with Acute Asthma Receiving a Multiple-Dose Protocol of Ipratropium Bromide Plus Albuterol in the Emergency Department
Authors: GUSTAVO J. RODRIGO, CARLOS RODRIGO
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We designed a larger, double-blind, randomized, prospective trial to test our hypothesis that patients with acute asthma given combination high dose therapy with ipratropium bromide (IB) and β2-agonists will have greater improvement in pulmonary function and fewer hospital admissions than those given β2-agonists alone. One hundred eighty patients (mean age ± SD, 34.3 ± 10.5 yr) who presented to an emergency department (ED) for treatment of an exacerbation of asthma (baseline FEV1 < 50% of predicted) were assigned in a randomized, double-blind fashion to receive albuterol and placebo (n = 92) or albuterol and IB (n = 88). Both drugs were administered through a metered-dose inhaler and spacer at 10-min intervals for 3 h (24 puffs or 2,880 μ g of albuterol and 504 μ g of IB each hour). Primary outcome measures were improvement in pulmonary function (FEV1 or peak expiratory flow [PEF]), and hospital admission rates. In both groups, pulmonary function improved significantly over baseline values (p < 0.01). Subjects who received IB had an overall 20.5% (95% CI: 2.6 to 38.4%) (p = 0.02) greater improvement in PEF and a 48.1% (95% CI: 19.8 to 76.4%) (p = 0.001) greater improvement in FEV1 from the control group. At the end of protocol (3 h), 39% (n = 36) of patients in the control group and 20% (n = 18) in the IB group were admitted (p = 0.01). The use of high doses of IB reduced the risk of hospital admission 49% (relative risk = 0.51, 95% CI: 0.31 to 0.83). Five (95% CI: 3 to 17) patients would need to be treated with high doses of IB to prevent a single admission. Kaplan-Meier-estimated curves of the proportion of patients who reached the discharge threshold during the 3 h of treatment, showed a significant difference in favor of the IB group (log-rank test = 0.005). A subgroup analysis showed that patients most likely to benefit from the addition of high doses of IB were those with more severe obstruction (FEV1 ⩽ 30% of predicted) and long duration of symptoms before the ED presentation ( ⩾ 24 h). On the contrary, previous use of inhaled β2-agonists did not modify the admission rate and the pulmonary function response to IB. In conclusion, our data support a substantial therapeutic benefit from the addition of IB to albuterol administered in high doses through MDI plus spacer, particularly in patients with FEV1 less than 30%, and with long duration of symptoms before the ED presentation ( ⩾ 24 h).
Endocardiac Pacemaker-Induced Diaphragmatic Contractions
Authors: Trevelyan E. Palmer
Journal: JAMA (1967)

PERMANENT implantable endocardiac pacemaker systems have greatly extended the surgical treatment of heart-block. Patients judged to be unfit for thoracotomy may now be offered substantial symptomatic relief with a relatively lowrisk operation employing local anesthesia. Early in the clinical experience of permanent endocardiac pacing, one expected electrode dislodgement, intermittent contact of the electrode due to myocardial contraction, rising myocardial impedance to electrode stimulation, predisposition to thrombosis by the large intravascular foreign body electrode, and possibly tricuspid insufficiency. Prior to treating the two patients described in this report, we had encountered only dislodgement and intermittent contact of the bipolar electrode. These complications have been uncommon and have been noted early in the postoperative period. They have been easily remedied by further manipulation through the same incisions, with the patient under local anesthesia. Recently, we have seen two patients who presented with vigorous diaphragmatic contractions noted approximately six weeks and four months
CERVICAL SYMPATHECTOMY FOR ANGINA PECTORIS: REPORT OF A CASE WITH DEXTRAL RADIATIONS OF PAIN
Authors: Philip King Brown
Journal: JAMA (1923)

<h3>History.</h3> —J. D., a special officer, entered the Southern Pacific Hospital, Dec. 11, 1922, in a state of collapse with marked cardiac decompensation, auricular fibrillation and dyspnea. Aug. 29, 1922, at 8 p. m., he came home worn out from a long day's work. He had been on a twelve-hour shift since July 1, with gradually increasing weakness and shortness of breath. He would have to stand outside his front door after climbing eleven stairs and get himself in hand before entering the house. He felt that he could not keep on much longer. At 9 p. m., August 29, after going to bed without supper, he had a sudden pain in the region of the heart and out to the right shoulder, vicelike and piercing. In a few minutes the pain radiated to the left shoulder, down the right arm to the elbow and across the lower chest. The
1105-171 Hip ratio cutoffs associated with metabolic risk factors and subclinical coronary atherosclerosis in nonobese asymptomatic men
Authors: Khurram Nasir, Romeu Meneghelo, Jose A Carvalho, Joel B Braunstein, Wendy S Post, Matthew J Buddoff, Roger S Blumenthal, Eduardo Mauricio, Armando Pereirinha, Raul D Santos
Journal: Journal of the American College of Cardiology (2004)
Unilateral Pseudogynecomastia: A Novel Work-Related Disease
Authors: S. Hanneken, R. Kruse, P. Dall, T. Ruzicka, N. J. Neumann
Journal: Annals of Internal Medicine (2004)

Letters16 March 2004Unilateral Pseudogynecomastia: A Novel Work-Related DiseaseS. Hanneken, MD, R. Kruse, MD, P. Dall, MD, T. Ruzicka, MD, and N. J. Neumann, MDS. Hanneken, MDFrom University of Duesseldorf, 40225 Duesseldorf, Germany., R. Kruse, MDFrom University of Duesseldorf, 40225 Duesseldorf, Germany., P. Dall, MDFrom University of Duesseldorf, 40225 Duesseldorf, Germany., T. Ruzicka, MDFrom University of Duesseldorf, 40225 Duesseldorf, Germany., and N. J. Neumann, MDFrom University of Duesseldorf, 40225 Duesseldorf, Germany.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-140-6-200403160-00034-w3 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Background: The distinction between gynecomastia, which affects breast glandular tissue (1, 2), and pseudogynecomastia, which affects only subcutaneous fat tissue (lipomastia), is essential (3, 4). Pseudogynecomastia can occur bilaterally and unilaterally and is mainly related to obesity.Objective: To describe a patient who developed pseudogynecomastia of his right breast caused by strenuous physical work over a 10-year period.Methods and Findings: On clinical examination, the patient, a 39-year-old man, had a significantly enlarged right breast with a horizontal skin fold of 6 to 7 cm. The enlargement extended to the right axilla and to the back (Figure). ...References1. Heufelder AE, Leinung MC, Northcutt RC. Holiday gynecomastia [Letter]. Ann Intern Med. 1992;116:877. [PMID: 1567108] LinkGoogle Scholar2. Couderc LJ, Clauvel JP. HIV-infection-induced gynecomastia [Letter]. Ann Intern Med. 1987;107:257. [PMID: 3605910] LinkGoogle Scholar3. Braunstein GD. Gynecomastia. N Engl J Med. 1993;328:490-5. [PMID: 8421478] CrossrefMedlineGoogle Scholar4. Lippens C, Ardies P, Van Steen A. Pseudogynecomastia. J Belge Radiol. 1990;73:528-9. [PMID: 2277017] MedlineGoogle Scholar5. Leask A, Holmes A, Abraham DJ. Connective tissue growth factor: a new and important player in the pathogenesis of fibrosis. Curr Rheumatol Rep. 2002;4:136-42. [PMID: 11890879] CrossrefMedlineGoogle Scholar6. Hishikawa K, Oemar BS, Nakaki T. Static pressure regulates connective tissue growth factor expression in human mesangial cells. J Biol Chem. 2001;276:16797-803. [PMID: 11278731] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From University of Duesseldorf, 40225 Duesseldorf, Germany. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byUnilateral Pseudogynecomastia: An Occupational Hazard in Manual Metal-Pressing Factories? 16 March 2004Volume 140, Issue 6Page: W-28KeywordsBreast tissueConnective tissueFatsFibrosisMammographyObesityPathogensPatient advocacySoft tissuesThorax ePublished: 16 March 2004 Issue Published: 16 March 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Role of Focal Adhesion Kinase and Phosphatidylinositol 3′-Kinase in Integrin Fibronectin Receptor-Mediated, Matrix Metalloproteinase-1–Dependent Invasion by Metastatic Prostate Cancer Cells
Authors: Zhao-Zhu Zeng, Yifeng Jia, Nathan J. Hahn, Sonja M. Markwart, Korrene F. Rockwood, Donna L. Livant
Journal: Cancer Research (2006)

Abstract α5β1 Integrin interacts with the PHSRN sequence of plasma fibronectin, causing constitutive invasion by human prostate cancer cells. Inhibition of this process reduces tumorigenesis and prevents metastasis and recurrence. In this study, naturally serum-free basement membranes were used as in vitro invasion substrates. Immunoassays were employed to dissect the roles of focal adhesion kinase (FAK), phosphatidylinositol 3′-kinase (PI3K), and protein kinase Cδ (PKCδ) in α5β1-mediated, matrix metalloproteinase-1 (MMP-1)–dependent invasion by metastatic human DU 145 prostate cancer cells. We found that a peptide composed of the PHSRN sequence induced rapid FAK phosphorylation at Tyr397 (Y397), a site whose phosphorylation is associated with kinase activation. The technique of RNA silencing [small interfering RNA (siRNA)] confirmed the role of FAK in PHSRN-induced invasion. PHSRN also induced the association of the p85-regulatory subunit of PI3K with FAK at a time corresponding to FAK phosphorylation and activation, and maximal PI3K activity occurred at this same time. The necessity of PI3K activity in both PHSRN-induced invasion and MMP-1 expression was confirmed by using specific PI3K inhibitors. By employing a specific inhibitor, Rottlerin, and by using siRNA, we also found that PKCδ, a PI3K substrate found in focal adhesions, functions in PHSRN-induced invasion. In addition, the induction of MMP-1 in PHSRN-treated DU 145 cells was shown by immunoblotting, and the role of MMP-1 in PHSRN-induced invasion was confirmed by the use of blocking anti-MMP-1 monoclonal antibody. Finally, a close temporal correspondence was observed between PHSRN-induced invasion and PHSRN-induced MMP-1 activity in DU 145 cells. (Cancer Res 2006; 66(16): 8091-9)
Decreased Selenium Levels in Acute Myocardial Infarction
Authors: Frans J. Kok
Journal: JAMA (1989)

To study the association between selenium status and the risk of myocardial infarction, we compared plasma, erythrocyte, and toenail selenium levels and the activity of erythrocyte glutathione peroxidase among 84 patients with acute myocardial infarction and 84 population controls. Mean concentrations of all selenium measurements were lower in cases than controls. The differences were statistically significant, except for the plasma selenium level. A positive trend in the risk of acute myocardial infarction from high to low toenail selenium levels was observed, which persisted after adjustment for other risk factors for myocardial infarction. In contrast, erythrocyte glutathione peroxidase activity was significantly higher in cases than controls (31.3 +/- 8.4 U/g of hemoglobin and 28.0 +/- 8.1 U/g of hemoglobin, respectively). Because the toenail selenium level reflects blood levels up to one year before sampling, these findings suggest that a low selenium status was present before the infarction and, thus, may be of etiologic relevance. The higher glutathione peroxidase activity in the cases may be interpreted as a defense against increased oxidant stress either preceding or following the acute event.
Targeted Delivery of siRNA to Macrophages for Anti-inflammatory Treatment
Authors: Sang-Soo Kim, Chunting Ye, Priti Kumar, Isaac Chiu, Sandesh Subramanya, Haoquan Wu, Premlata Shankar, N Manjunath
Journal: Molecular Therapy (2010)

Inflammation mediated by tumor necrosis factor-alpha (TNF-alpha) and the associated neuronal apoptosis characterizes a number of neurologic disorders. Macrophages and microglial cells are believed to be the major source of TNF-alpha in the central nervous system (CNS). Here, we show that suppression of TNF-alpha by targeted delivery of small interfering RNA (siRNA) to macrophage/microglial cells dramatically reduces lipopolysaccharide (LPS)-induced neuroinflammation and neuronal apoptosis in vivo. Because macrophage/microglia express the nicotinic acetylcholine receptor (AchR) on their surface, we used a short AchR-binding peptide derived from the rabies virus glycoprotein (RVG) as a targeting ligand. This peptide was fused to nona-D-arginine residues (RVG-9dR) to enable siRNA binding. RVG-9dR was able to deliver siRNA to induce gene silencing in macrophages and microglia cells from wild type, but not AchR-deficient mice, confirming targeting specificity. Treatment with anti-TNF-alpha siRNA complexed to RVG-9dR achieved efficient silencing of LPS-induced TNF-alpha production by primary macrophages and microglia cells in vitro. Moreover, intravenous injection with RVG-9dR-complexed siRNA in mice reduced the LPS-induced TNF-alpha levels in blood as well as in the brain, leading to a significant reduction in neuronal apoptosis. These results demonstrate that RVG-9dR provides a tool for siRNA delivery to macrophages and microglia and that suppression of TNF-alpha can potentially be used to suppress neuroinflammation in vivo.
Diagnostic potential of amyl nitrite and nitroglycerin
Authors: S. Vaisrub
Journal: JAMA (1973)

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How homophobia is fuelling Africa's HIV epidemic
Authors: B. Roehr
Journal: BMJ (2010)

P2X receptors (P2XRs) are ion channels gated by synaptically released ATP. The P2X4 is the most abundant P2XR subtype expressed in the central nervous system and to date is the most ethanol-sensitive. In addition, genomic findings suggest that P2X4Rs may play a role in alcohol intake/preference. However, little is known regarding how ethanol causes the inhibition of ATP-gated currents in P2X4Rs. We begin to address this issue by investigating the effects of ethanol in wild-type and mutant D331A and M336A P2X4Rs expressed in human embryonic kidney (HEK) 293 cells using whole-cell patch-clamp methods. The results suggest that residues D331 and M336 play a role in P2X4R gating and ethanol inhibits channel functioning via a mechanism different from that in other P2XRs. Key findings from the study include: 1) ethanol inhibits ATP-gated currents in a rapid manner; 2) ethanol inhibition of ATP-gated currents does not depend on voltage and ATP concentration; 3) residues 331 and 336 slow P2X4 current deactivation and regulate the inhibitory effects of ethanol; and 4) ethanol effects are similar in HEK293 cells transfected with P2X4Rs and cultured rat hippocampal neurons transduced with P2X4Rs using a recombinant lentiviral system. Overall, these findings provide key information regarding the mechanism of ethanol action on ATP-gated currents in P2X4Rs and provide new insights into the biophysical properties of P2X4Rs.