tbuckley/cabot-search huggingface dataset:
Asthma in Childhood
Authors: C. B. S. Fuller
Journal: BMJ (1952)

analysed to justify an assumption that similar real differ- ences in the frequency of their use would occur in the general population of asthmatic patients.The effect of any one inhalant was found to vary greatly from patient to patient and on different occasions for the same patients. Summary and ConclusionsAn experiment was designed to compare the need for recourse to four inhalants-riddobron, brovon, neo- epinine No. 2, and neb.adrenal.et atrop.co.(N.F.)
Presence of endothelial dysfunction is the major determinant of maladaptive vascular remodeling in brachial arteries of untreated hypertensive patients
Authors: Tomoo Furumoto, Satoshi Fujii, Keiko Nishihara, Satoshi Yamada, Hisao Onozuka, Kaoru Komuro, Kazutomo Goto, Wu Di, Taisei Mikami, Hirotaka Nishijima, Akira Kitabatake
Journal: Journal of the American College of Cardiology (2003)
Hepatitis B viral markers in severe viral hepatitis: Influence of steroid therapy
Authors: Harry B. Greenberg, William S. Robinson, Michael C. Knauer, Peter B. Gregory
Journal: Hepatology (1981)

In our double-blind randomized trial of methylprednisolone vs. placebo in severe viral hepatitis, 16 patients with hepatitis B (8 on steroid, 8 on placebo) were followed for at least 4 weeks. Four of the eight patients receiving methylprednisolone eventually died and all patients on placebo survived. Despite marked reduction in serum IgG in steroid-treated patients, the decline in HB s Ag titer and disappearance of Dane particle markers was the same in both treatment groups. A nonspecific depression of anti-HBc was noted in patients given steroid. There is no evidence that corticosteroid therapy accelerates viral replication when the acute hepatitis is severe.
Monoclonal Antibody 4C5 Immunostains Human Melanomas and Inhibits Melanoma Cell Invasion and Metastasis
Authors: Dimitris Stellas, Andreas Karameris, Evangelia Patsavoudi
Journal: Clinical Cancer Research (2007)

Tumor cell metastasis constitutes a major problem in the treatment of cancer. Because the cure rate of metastatic tumors is very low, new therapeutic approaches are needed. Heat shock protein 90 (HSP90) is a molecular chaperone that is recognized as a new target for the treatment of cancer. Here, we examine the value of a monoclonal antibody (mAb) against HSP90, mAb 4C5, as a potential marker in malignant melanomas. Moreover, we investigate the possibility to use mAb 4C5 as an inhibitor of melanoma cell invasion and metastasis.Paraffin blocks of formalin-fixed human melanoma tumor tissues were used to prepare tissue microarrays. The B16 F10 melanoma cell line was used in all the in vitro experiments. To assess melanoma cell invasion, the wound-healing assay and the Matrigel invasion assay were applied. To evaluate the effect of mAb 4C5 on tumor metastasis, we used an experimental model of metastatic melanoma.Immunohistochemical studies done on a panel of malignant melanomas showed positive immunostaining with mAb 4C5 in all cases. mAb 4C5 inhibits B16 F10 cell invasion by binding to surface HSP90 because it is not internalized. mAb 4C5 significantly inhibits melanoma metastasis in C57BL/6 mice inoculated with B16 F10 cells.mAb 4C5 could be potentially used as a novel specific marker for malignant melanomas. mAb 4C5 inhibits melanoma cell invasion in vitro by binding to cell surface HSP90 expressed on B16 F10 melanoma cells. Finally, this antibody significantly inhibits melanoma metastasis, thus rendering it a potential therapeutic agent for the treatment of cancer metastasis.
Erucylphosphohomocholine, the first intravenously applicable alkylphosphocholine, is cytotoxic to acute myelogenous leukemia cells through JNK- and PP2A-dependent mechanisms
Authors: A M Martelli, V Papa, P L Tazzari, F Ricci, C Evangelisti, F Chiarini, C Grimaldi, A Cappellini, G Martinelli, E Ottaviani, P Pagliaro, S Horn, J Bäsecke, L H Lindner, H Eibl, J A McCubrey
Journal: Leukemia (2010)
Health risks of overseas travel
Authors: Ulf R Dahle, Fernanda C Petersen
Journal: BMJ (2004)

Editor—Dobson comments on an article that is to appear in Travel Medicine and Infectious Disease, in which the researchers call for more education about the prevention of malaria and other infectious diseases.1,2 ​




Figure 1



Credit: CDC




We recently returned from the Rio Negro area, 40 km from Manaus city in the Amazon, Brazil. During the first trimester of 2003 Manaus experienced an 815% increase in cases of malaria compared with the same period in 2002.3 This means 223 new cases daily, and close to 17 000 notifications for the trimester.3

Despite this increase, most Americans and Europeans whom we met did not take malaria prophylaxis. Also, most were not vaccinated against yellow fever or hepatitis A. Many found it ridiculous that we were taking Malarone (atovaquone plus proguanil) and had received vaccines before we travelled.

The local guides argued that malaria prophylaxis was unnecessary on the Rio Negro since mosquitoes do not thrive in the acidic waters of this part of the river. They were clearly well educated in biology and infectious diseases but apparently forgot that all tourists need to travel through high risk areas to reach the Rio Negro delta.

Many young Europeans and Americans seem not to be used to taking responsibility for their own health. Decades of well functioning public health systems, vaccination programmes, easy access to “high tech” health services, etc, seem to leave young people naive and ignorant about infectious diseases.
Idiopathic Alveolar Hypoventilation: Clinical Spectrum
Authors: GEORGE G. RHOADS
Journal: Annals of Internal Medicine (1969)

Seven patients had varying degrees of impaired pulmonary function but in other respects resembled patients with idiopathic alveolar hypoventilation. These patients were characterized by chronic cor pulmonale; a diminished ventilatory response to inhaled carbon dioxide; carbon dioxide retention disproportionate to the extent of airflow obstruction; and by the ability to voluntarily hyperventilate and return PaO2 and PaCO2 to normal or near normal levels. These studies suggest that the clinical spectrum of idiopathic alveolar hypoventilation, that is, inappropriate or unexplained carbon dioxide retention, can be extended to include some patients with obstructive and restrictive lung disease and that respiratory insensitivity to carbon dioxide is commoner than previously recognized.
The Lupus Anticoagulant: A Confusing Misnomer
Authors: JOSEPH GOLBUS
Journal: Annals of Internal Medicine (1987)

Letters and Corrections1 June 1987The Lupus Anticoagulant: A Confusing MisnomerJOSEPH GOLBUS, M.D., DAVID A. FOX, M.D.JOSEPH GOLBUS, M.D.Search for more papers by this author, DAVID A. FOX, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-106-6-911_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The lupus anticoagulant is an antibody that reacts in vitro with the prothrombin activator complex (factor Xa, factor V, and phospholipid) (1). First reported in 1952, increased attention has been recently focused on this inhibitor and its physiologic effects. Contrary to its designation as an anticoagulant, these antibodies are now strongly linked to invivo thrombotic events (2-5). We have recently seen a patient where this obvious misnomer has caused confusion leading to a poor clinical outcome.A 21-year-old woman had a 3-year history of systemic lupus erythematosus, manifested by a malar rash, arthralgias, pleuritis, Raynaud phenomenon, thrombocytopenia,...References1. FEINSTEINRAPAPORT DS. Acquired inhibitors of blood coagulation. Prog Hemost Thromb. 1972;1:75-95. MedlineGoogle Scholar2. MUEHHERBSTRAPAPORT JKS. Thrombosis in patients with the lupus anticoagulant. Ann Intern Med. 1980;92:156-9. LinkGoogle Scholar3. BOEYCOLACOGJARAVIELKONLOIZOUHUGHES MCAKSG. Thrombosis in systemic lupus erythematosus: striking association with the presence of circulating lupus anticoagulant. Br Med J. 1983;287:1021-3. CrossrefMedlineGoogle Scholar4. ELIASELDOR MA. Thromboembolism in patients with the "lupus"-type circulating anticoagulant. Arch Intern Med. 1984;144:510-5. CrossrefMedlineGoogle Scholar5. BRANCHSCOTTKOCHENOURHERSHGOLD DJNE. Obstetric complications associated with the lupus anticoagulant. N Engl J Med. 1985;313:1322-6. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: JOSEPH GOLBUS, M.D.; DAVID A. FOX, M.D.Affiliations: University of Michigan Medical Center Ann Arbor, MI 48109-0358 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1987Volume 106, Issue 6Page: 911-911KeywordsAnticoagulantsArthralgiaLupus erythematosusPhospholipidsRashes ePublished: 1 December 2008 Issue Published: 1 June 1987 PDF downloadLoading ...
Total energy expenditure and carbohydrate oxidation are increased in the human immunodeficiency virus lipodystrophy syndrome
Authors: Lisa A. Kosmiski, Daniel R. Kuritzkes, Teresa A. Sharp, Jere T. Hamilton, Kenneth A. Lichtenstein, Cecilia L. Mosca, Gary K. Grunwald, Robert H. Eckel, James O. Hill
Journal: Metabolism (2003)
Regular review: Management of urinary incontinence in women
Authors: R. Thakar, S. Stanton
Journal: BMJ (2000)

<h3>Background</h3> Antibodies against citrullinated peptides have gained special importance in the diagnosis of rheumatoid arthritis (RA) (1,2). <h3>Objectives</h3> This study aims to investigate the diagnostic sensitivity and specificity of anti-mutated citrullinated vimentin (anti-MCV) antibodies for rheumatoid arthritis (RA) in comparison to IgM RF and anti-CCP and to assess their clinical significance particularly as a marker of RA activity. <h3>Methods</h3> 60 patients with different rheumatic diseases 40 patients with RA and 20 patients with other rheumatic diseases (disease controls) were recruited from Ain Shams University Hospitals, and 20 persons (healthy controls) All participants underwent history taking, clinical examination, laboratory and radiological investigations, and calculation of disease activity score DAS-28 for each RA patient. Enzyme-linked immunosorbent assay (ELISA) techniques were used to detect RF-IgM, anti-CCP antibodies, and anti-MCV antibodies <h3>Results</h3> The sensitivity of anti-MCV antibodies was 95% with 97.1% specificity. For anti-CCP antibodies the sensitivity was 95% and the specificity was 100%. The sensitivity of RF was 72.5% with 97.1% specificity. Anti-CCP antibodies have higher diagnostic specificity and positive predictive value than RF and anti-MCV antibodies. The best cut-off value for the anti-MCV test was found at 22.7 U/L, while that for Anti-CCP antibodies and RF were 20 u/l and 44 IU/ml respectively. Of RA patients with positive RF, 86.2% were anti-MCV antibodies positive, including only 6.8% with negative Anti-CCP. Of patients with negative RF, 81.8% were positive for anti-MCV, including 9% who tested negative for anti-CCP. <h3>Conclusions</h3> Our results suggest that anti-MCV antibodies may be valuable for diagnosing RA and that, it may be better to assay both anti-MCV and anti-CCP in RF -negative RA patients without replacing them. Long-term study is required to find out whether anti-MCV antibodies can be used as predictive test for incidence of RA. <h3>References</h3> Klareskog L, Rönnelid J, Lundberg K, Padyukov L, Alfredsson L: Immunity to citrullinated proteins in rheumatoid arthritis. Annu Rev Immunol 2008, 26: 651-675. Shmerling RH, Delbanco TL: How useful is the rheumatoid factor? An analysis of sensitivity, specificity and predictive value. Arch Intern Med. 1992,152: 2417–2420. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5120
Heart Rate Variability in Patients With Atrial Fibrillation Is Related to Vagal Tone
Authors: Maarten P. van den Berg, Jaap Haaksma, Jan Brouwer, Robert G. Tieleman, G. Mulder, Harry J. G. M. Crijns
Journal: Circulation (1997)

Background Analysis of heart rate variability (HRV) has thus far not been applied in patients with atrial fibrillation, probably because of the presumed absence of any form of patterning of the ventricular rhythm, particularly vagally mediated respiratory arrhythmia. However, such patterning is theoretically conceivable given the function of the atrioventricular node in atrial fibrillation and its susceptibility to autonomic influences. Methods and Results Sixteen patients (mean age, 56±4 years) with long-term atrial fibrillation on fixed doses of digoxin or verapamil were studied; 12 healthy men in sinus rhythm were used as control subjects. HRV (standard deviation of RR intervals [SD], coefficient of variance [CV], the root-mean-square of successive difference [RMSSD], and low-frequency [LF] and high-frequency power [HF]) was analyzed during 500 RR intervals at baseline, after administration of propranolol (0.2 mg/kg IV), and after subsequent administration of methylatropine (0.02 mg/kg IV). HRV at baseline and changes in HRV after methylatropine were then related to vagal tone (vagal cardiac control), quantified as the decrease in mean RR after methylatropine. Baseline HRV was higher in the atrial fibrillation group than in the control group; after propranolol, HRV increased in both groups; after methylatropine, HRV neared zero in the control group, whereas it returned to baseline values in the atrial fibrillation group. SD, RMSSD, LF, and HF at baseline were significantly ( P &lt;.05) correlated with vagal tone in the control group but also in the atrial fibrillation group (correlation coefficients of .60, .61, .57, and .64, respectively). Even stronger correlations were observed between changes in these parameters after methylatropine and vagal tone, particularly in the atrial fibrillation group (correlation coefficients of .89, .87, .72, and .90, respectively). Conclusions This study shows that HRV in patients with atrial fibrillation is related to vagal tone.
Epigenetic Changes in Pediatric Solid Tumors: Promising New Targets
Authors: Elizabeth R. Lawlor, Carol J. Thiele
Journal: Clinical Cancer Research (2012)

Abstract Cancer is being reinterpreted in the light of recent discoveries related to the histone code and the dynamic nature of epigenetic regulation and control of gene programs during development, as well as insights gained from whole cancer genome sequencing. Somatic mutations in or deregulated expression of genes that encode chromatin-modifying enzymes are being identified with high frequency. Nowhere is this more relevant than in pediatric embryonal solid tumors. A picture is emerging that shows that classic genetic alterations associated with these tumors ultimately converge on the epigenome to dysregulate developmental programs. In this review, we relate how alterations in components of the transcriptional machinery and chromatin modifier genes contribute to the initiation and progression of pediatric solid tumors. We also discuss how dramatic progress in our understanding of the fundamental mechanisms that contribute to epigenetic deregulation in cancer is providing novel avenues for targeted cancer therapy. Clin Cancer Res; 18(10); 2768–79. ©2012 AACR.
Lentivector Transduction Improves Outcomes Over Transplantation of Human HSCs Alone in NOD/SCID/Fabry Mice
Authors: Natalia Pacienza, Makoto Yoshimitsu, Nobuo Mizue, Bryan CY Au, James CM Wang, Xin Fan, Toshihiro Takenaka, Jeffrey A Medin
Journal: Molecular Therapy (2012)

Fabry disease is a lysosomal storage disorder caused by a deficiency of α-galactosidase A (α-gal A) activity that results in progressive globotriaosylceramide (Gb3) deposition. We created a fully congenic nonobese diabetic (NOD)/severe combined immunodeficiency (SCID)/Fabry murine line to facilitate the in vivo assessment of human cell-directed therapies for Fabry disease. This pure line was generated after 11 generations of backcrosses and was found, as expected, to have a reduced immune compartment and background α-gal A activity. Next, we transplanted normal human CD34+ cells transduced with a control (lentiviral vector-enhanced green fluorescent protein (LV-eGFP)) or a therapeutic bicistronic LV (LV-α-gal A/internal ribosome entry site (IRES)/hCD25). While both experimental groups showed similar engraftment levels, only the therapeutic group displayed a significant increase in plasma α-gal A activity. Gb3 quantification at 12 weeks revealed metabolic correction in the spleen, lung, and liver for both groups. Importantly, only in the therapeutically-transduced cohort was a significant Gb3 reduction found in the heart and kidney, key target organs for the amelioration of Fabry disease in humans. Fabry disease is a lysosomal storage disorder caused by a deficiency of α-galactosidase A (α-gal A) activity that results in progressive globotriaosylceramide (Gb3) deposition. We created a fully congenic nonobese diabetic (NOD)/severe combined immunodeficiency (SCID)/Fabry murine line to facilitate the in vivo assessment of human cell-directed therapies for Fabry disease. This pure line was generated after 11 generations of backcrosses and was found, as expected, to have a reduced immune compartment and background α-gal A activity. Next, we transplanted normal human CD34+ cells transduced with a control (lentiviral vector-enhanced green fluorescent protein (LV-eGFP)) or a therapeutic bicistronic LV (LV-α-gal A/internal ribosome entry site (IRES)/hCD25). While both experimental groups showed similar engraftment levels, only the therapeutic group displayed a significant increase in plasma α-gal A activity. Gb3 quantification at 12 weeks revealed metabolic correction in the spleen, lung, and liver for both groups. Importantly, only in the therapeutically-transduced cohort was a significant Gb3 reduction found in the heart and kidney, key target organs for the amelioration of Fabry disease in humans.
Doctors' chambers---pipe dream or blueprint for the future?
Authors: K. Burke
Journal: BMJ (2002)

It sounds like a marvellous idea—a cross between John Mortimer's Rumpole of the Bailey and James Herriot's All Creatures Great and Small . But are medical chambers a pipe dream or a serious way forward for the NHS?

Since the BMA produced a discussion paper on setting up medical chambers last May, some consultants have begun collaborating in private practice under formal partnerships and limited companies, while continuing on 10/11ths NHS contracts. But how far do such part time collaborations go in testing the private chambers concept, and what effect would private chambers have if they did spread across the NHS?

According to the BMA's concept of medical chambers, consultants would become self employed, free standing practitioners, working from private chambers with fellow clinicians, who charge the NHS per service supplied. The beauty of it would be more independence, possibly higher incomes, and no more management or administrative duties unless one opted into these (and charged accordingly).

Part time private collaborations among doctors who sell their services to the NHS are widespread across pathology and anaesthetics, and there is talk about setting up such arrangements in cardiothoracic surgery, ophthalmology, and orthopaedics.

Pathology is suitable for the group approach because of severe …
Depression and survival following myocardial infarction
Authors: T. J. Cleophas
Journal: JAMA (1994)

To the Editor.  —The data of Frasure-Smith et al 1 identifying mental depression as a major determinant of cardiac death after MI are very impressive and will no doubt have a large impact. However, I have three points.  First, the study found a fivefold higher mortality rate among depressed MI survivors. I think that this study may suffer from some selection bias. The two groups were tested for symmetry of covariates. However, their psychosocial factors before the MI were not taken into account and were probably largely asymmetric. I assume that many of the patients who were depressed after the MI were so before, and that their depression was, in fact, so severe that it led to the MI in the first place. Therefore, these are a selected group of severely depressed people and their mortality rates may not be representative for mortality rates of survivors of MI who were
Combination Genetic Therapy to Inhibit HIV-1
Authors: David S. Strayer, Francisco Branco, Julien Landré, Mohamad BouHamdan, Farida Shaheen, Roger J. Pomerantz
Journal: Molecular Therapy (2002)

Compared with single agents, combination antilentiviral pharmacotherapy targets multiple HIV-1 functions simultaneously, maximizing efficacy and decreasing chances of escape mutations. Combination genetic therapy could theoretically enhance efficacy similarly, but delivery of even single genes to high percentages of hematopoietic cells or their derivatives has proven problematic. Because of their high efficiency of gene delivery, we tested recombinant SV40-derived vectors (rSV40s) for this purpose. We made six rSV40s, each carrying a different transgene that targeted a different lentiviral function. We tested the ability of these constructs, individually and in double and triple combinations, to protect SupT1 human T lymphoma cells from HIV-1 challenge. Single chain antibodies (SFv) against CXCR4 and against HIV-1 reverse transcriptase (RT) and integrase (IN) were used, as were polymeric TAR decoys (PolyTAR) and a dominant-negative mutant of HIV-1 Rev (RevM10). Immunostaining showed that virtually all doubly treated cells expressed both transgenes. All transgenes individually protected from HIV-1 but, except for anti-CXCR4 SFv, their effectiveness diminished as challenge doses increased from 40 through 2500 tissue culture infectious dose50 (TCID50)/106 cells. However, all combinations of transgenes protected target cells better than individual transgenes, even from the highest challenge doses. Thus, combination gene therapies may inhibit HIV-1 better than single agents, and rSV40s may facilitate delivery of multigene therapeutics.
Rubella Vaccination of Hospital Employees
Authors: Stephen R. Preblud
Journal: JAMA (1981)

Before rubella vaccine was introduced in the United States in 1969, rubella was primarily a disease of elementary school-aged children.<sup>1</sup>However, outbreaks have also occurred in adolescent and young adult populations (eg, military recruits<sup>2</sup>) because 15% to 20% of persons in these age groups were susceptible.<sup>1,3</sup>Widespread vaccination of young children has successfully interrupted the characteristic six- to nine-year rubella epidemic cycle, reduced overall reported endemic rubella activity by 70%, and decreased the number of reported cases in children younger than 15 years by 85%.<sup>1</sup> On the other hand, the risk of rubella among adolescents and young adults, who now account for most reported cases, has declined less dramatically, as evidenced by their unchanged susceptibility rate<sup>1,4</sup>and by outbreaks in secondary schools,<sup>5</sup>colleges,<sup>5-7</sup>and military bases.<sup>3,8</sup>Because hospital employees are likely to be as susceptible as the general public,<sup>9-14</sup>outbreaks in