tbuckley/cabot-search huggingface dataset:
Combined Aortic and Mitral Incompetence.
Authors: Kenneth I. Shine
Journal: Annals of Internal Medicine (1968)

s1 May 1968Combined Aortic and Mitral Incompetence.Kenneth I. Shine, M.D., Roman W. DeSanctis, M.D., F.A.C.P., Charles A. Sanders, M.D., W. Gerald Austen, M.D.Kenneth I. Shine, M.D.Search for more papers by this author, Roman W. DeSanctis, M.D., F.A.C.P.Search for more papers by this author, Charles A. Sanders, M.D.Search for more papers by this author, W. Gerald Austen, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1161_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe problem of mitral incompetence complicating aortic regurgitation was analyzed in 39 patients. In each case the diagnosis was confirmed either at cardiac surgery or autopsy.Three groups were defined according to the cause of mitral insufficiency: group I (12 patients)—rupture of mitral chordae tendineae; group II (13 patients)—mitral insufficiency as a consequence of advanced left ventricular failure; and group III (14 patients)—mitral insufficiency due to rheumatic mitral incompetence.The clinical, hemodynamic, and radiographic features of the three groups were compared. Groups I and II showed many common features, including male predominance, preservation of sinus rhythm, and a small left... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Massachusetts PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1968Volume 68, Issue 5Page: 1161-1162KeywordsAutopsyCardiac surgeryHemodynamicsMitral insufficiency Issue Published: 1 May 1968 PDF DownloadLoading ...
Abstract 3209: The WRN RecQ helicase acts as a tumor suppressor in pancreatic adenocarcinoma
Authors: Stephen G. Chun, Nelson S. Yee, Fang Qi, Richard Allsopp, Philip M. Davy, Keith S. Fong, Michele Carbone, Peter K. Bryant-Greenwood
Journal: Cancer Research (2010)

Abstract The vast majority of pancreatic adenocarcinoma is diagnosed in the geriatric population, and genes involved in cellular senescence such as the WRN-encoded RecQ helicase/exonuclease may be involved in pancreatic oncogenesis. Accumulating evidence suggests that WRN is a tumor suppressor gene (TSG), as a variety of cancers including pancreatic adenocarcinoma are associated with its epigenetic silencing or loss-of-function mutations. We hypothesize that wild-type WRN protects pancreatic epithelia from malignant transformation by regulating cell cycle progression and cell growth. First, we characterized a pancreatic adenocarcinoma cell line established from a human cadaver with Werner's syndrome (WS-Panc). WS-Panc had two loss-of-function mutations of WRN, formed adherent colonies in vitro, and expressed the pancreatic ductal epithelial marker cytokeratin 7. No oncogenic mutations of the epidermal growth factor receptor (EGFR), K-Ras nor B-Raf were detected by polymerase chain reaction (PCR), and immunologic assays revealed over-expression of lysyl oxidase-like 2, p53, and ß-catenin in WS-Panc. Fluorescent in situ hybrdization showed that WS-Panc over-expresses EGFR. Cytogenetic analyses showed normal karyotype. Strong telomerase activity was detected in WS-Panc by the Telomere Repeat Amplification Protocol. To test the hypothesis that WRN is a TSG, we forced ectopic expression of wild-type WRN in WS-Panc and are analyzing the biological properties and molecular features of transfected cells. Consistent with an anti-proliferative effect, wild-type WRN mRNA levels are uniformly repressed in a panel of sporadic pancreatic cancer cell lines from the American Type Culture Collection as shown by quantitative real-time PCR. In summary, we provide evidence that WRN is a TSG in pancreatic epithelia using WS-Panc and other pancreatic cancer cell lines. WS-Panc is the first cancer cell line carrying WRN loss-of-function mutations that represents a unique translational resource to elucidate WRN in the neoplastic state. Ongoing investigation of WRN in primary pancreatic cancer tissue and tumor models in vivo are expected to elucidate mechanistic links between aging and pancreatic cancer for the purpose of developing efficacious interventional strategies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3209.
NHS criticised for lax control over drugs industry
Authors: Zosia Kmietowicz
Journal: BMJ (2005)

Links between the pharmaceutical industry and the UK Department of Health have become so intertwined that the public's health is being put at risk, says a highly critical report from a cross party group of MPs, published this week. The much anticipated report cites multiple failings at the United Kingdom's drug regulatory body for not scrutinising thoroughly enough data from companies seeking licences for new drugs and for not monitoring side effects adequately.

It also blames lax controls at the Department of Health for allowing pharmaceutical companies to have expanded influence over the public and the medical profession, which has led to overprescribing by doctors and an unhealthy reliance on medicines by the public.

The report, from the House of Commons health select committee, recommends a …
Relevance of colour vision and diabetic retinopathy to self-monitoring of blood glucose.
Authors: K Graham, C M Kesson, H B Kennedy, J T Ireland
Journal: BMJ (1980)

A study was performed to determine the effect of colour vision defects and diabetic retinopathy on diabetic patients9 ability to use a visual method of measuring their own blood glucose concentrations. Forty-eight diabetics whose colour vision and retinal status was assessed by an ophthalmologist carried out 311 blood glucose estimations using oxidase-peroxidase test strips which were then compared with laboratory values. There was a trend towards poor performance with advancing age but neither colour vision nor diabetic retinopathy had a significant effect on patients9 ability to use this visual method of estimating blood glucose concentrations. The vast majority of diabetics who will benefit from being able to monitor their own blood glucose control should have no difficulty in using a visual method of testing, even if they do have defects of colour vision.
HER2 and HER3 cooperatively regulate tumor cell growth and determine sensitivity to the HER kinase inhibitor TAK-285.
Authors: S Takagi, A Hayashi, Y Ohta
Journal: Cancer Research (2009)

Abstract Abstract #3155 Background: The HER (ErbB) receptor family plays a major role in the proliferation of tumor cells. Overexpression of these receptors occurs in breast and a variety of cancers and correlates with poor prognosis. We have identified TAK-285, a potent, selective and orally bioavailable small molecule inhibitor of HER kinases. TAK-285, which is currently in clinical trials for the treatment of solid tumors, inhibits EGFR (also known as ErbB1 or HER1) and HER2 (also known as ErbB2) and exerts clear anti-proliferative activity in in vitro and in vivo tumor models. Here, we elucidated the determinants of TAK-285 anti-tumor activity in vitro in a panel of human cancer cell lines.&amp;#x2028; Methods: Cell growth inhibition assay was performed using sulforodamine B staining method or CellTiter-GloTM assay (Promega). Candidate gene expressions were measured by quantitative PCR. Associations between the IC50 values and the candidate gene expressions were statistically analysed.&amp;#x2028; Results: TAK-285 exerted anti-proliferative effects in all of cell lines tested in a dose dependent manner but the effects ranged widely (IC50: 0.011-over 10 µmol/L). Statistical analysis showed an inverse correlation between sensitivity to TAK-285 (IC50 values) and HER2 or HER3 (also known as ErbB3) gene expression. PTEN or IGF-1R gene expression, reported to be involved in trastuzumab resistance, was not correlated with TAK-285 sensitivity. Immunoblot analysis revealed that HER2 and HER3 are coexpressed in most TAK-285 sensitive cells and TAK-285 inhibited phosphorylation of HER3. Because HER3 does not possess kinase activity, this suggests that HER3 is trans-phosphorylated by HER2. Knockdown of HER3 using siRNA inhibited tumor cell growth in TAK-285 sensitive cells but not in TAK-285 insensitive cells.&amp;#x2028; Conclusion: These results suggest that HER2 and HER3 mainly regulate tumor cell growth in TAK-285 sensitive cells and could be used as a molecular marker to select patients who are likely to respond to TAK-285. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3155.
Drowning in Paint
Authors: Martin I. Gold
Journal: JAMA (1967)

WORKING with petroleum solvents in unventilated tanks and pits is hazardous.<sup>1-4</sup>The following is an account of an unusual accident in which two prisoners who were working in a vat were exposed to volatile solvents. An absolutely bizarre feature of this accident is the face-down drowning of the two men in 10 inches of paint residue. We were unable to uncover a similar report of what amounted to actual paint-drowning. <h3>Report of Cases</h3> At noon on Jan 12, 1965, anesthesia personnel at University Hospital were summoned to the emergency room to assist in the airway management for two prisoners from the Maryland House of Correction in Jessup. The prisoners were among a group of seven occupied in cleaning a giant, unventilated paint vat, the bottom of which was filled with approximately 10 inches of residue. The two prisoners, with questionably effective protective masks, were at the bottom of the
Corrosive acid ingestion in man - a clinical and endoscopic study.
Authors: J B Dilawari, S Singh, P N Rao, B S Anand
Journal: Gut (1984)

Sixteen patients with corrosive acid ingestion were studied. The majority of patients (n = 10) had ingested sulphuric acid, and three other patients had ingested hydrochloric acid. The extent and severity of upper gastrointestinal tract injury was determined by fibreoptic endoscopy and necropsy. All the patients had oesophageal and gastric involvement but the duodenum was spared in the majority. The injury was not considered as mild (grade I) in any of these patients; five patients having moderate (grade II) and 10 patients having severe (grade III) injury. Complications and mortality occurred only in patients with grade III injury. Feeding jejunostomy for nutritional support was used in five patients (all grade III) with good results.
Analysis of N‐ras gene mutations in acute myeloid leukemia by allele specific restriction analysis
Authors: A. V. Todd, C. M. Ireland, T. J. Radloff, H. Kronenberg, H. J. Iland
Journal: American Journal of Hematology (1991)

Abstract N‐ras gene activation occurs via single base substitutions in codons 12, 13, and 61. We have developed a rapid screening method, termed allele specific restriction analysis (ASRA), for detection of N‐ras mutations at these three critical codons in acute myeloid leukemia (AML). Patient DNA samples are amplified by the polymerase chain reaction (PCR) by using primers that induce restriction sites in normal but not mutant N‐ras alleles. We have used ASRA to identify 5 point mutations in four out of 19 patients at initial presentation of de novo AML. Three patients had one mutation at codon 12, 13, or 61 respectively, while a fourth patient had concurrent mutations at codons 12 and 13. N‐ras mutations were more common in patients over 65 years of age (P &lt; 0.04), but did not correlate with FAB classification, attainment of complete remission, disease free survival, or overall survival. ASRA can also be used as the first step in a more sensitive approach to the detection of ras mutations. When ASRA was combined with allele specific oligonucleotide (ASO) hybridization the sensitivity and specificity of these assays were increased. This allowed identification of additional low level mutations in two patients. The data presented here constitute the first complete analysis of N‐ras mutations in leukemia by ASRA and include the first identification of three concurrent N‐ras mutations in a single leukemic patient. By facilitating sensitive sequential studies, ASRA should contribute to our understanding of the role of N‐ras mutations in leukemogenesis.
METHODS OF TEACHING CLINICAL MEDICINE.Read before a Pedagogic Section of the Pan-American Medical Congress, Washington, September, 1893.
Authors: FREDERICK C. SHATTUCK
Journal: JAMA (1893)

Whether there is anything perfect in this world, I do not know. That it is possible to improve the teaching of clinical medicine in this country, at least, I feel quite sure; at the same time, also, I recognize the advance which is certainly making, and am, convinced that this will continue. We believe that the best is none too good for us, and propose to have it. To hasten and secure progress in the future it is well to understand and consider the past, and the lines along which evolution has worked to bring us where we are. We must also bear in mind the local conditions, with the advantages and disadvantages which they entail. The problems are, to make the best of what we have got, to get more, and gradually to surmount the bars to progress, whether these are accidental or inherent in the spirit and institutions
LOCALIZATION OF STREPTOCOCCAL ANTIGENS IN TISSUES
Authors: Melvin H. Kaplan
Journal: The Journal of Experimental Medicine (1958)

A method has been described for the detection of streptococcal antigens in tissues using the indirect immunofluorescent technique. This method has been applied to the histologic distribution in the mouse of M protein of types 1, 5, 12, and 19. Histologic localization of these M proteins was similar, and their rates of disappearance from the tissues were comparable. The major sites of deposition were the endocardium and adjacent subendocardium of the heart, alveolar walls of the lung, glomerular tufts of the kidney, and reticulo-endothelial cells of liver, spleen, lymph nodes, and adrenal gland. M protein was distributed in considerably lesser concentration in capillary endothelium and connective tissue sites in myocardium, kidney, skin, and gastrointestinal tract. Traces were also present in adrenal cortical cells. It was observed only rarely in cell nuclei. After injection of 0.5 mg. M protein fraction, the concentration of antigen diminished to undetectable levels in all organ sites by 4 days, except in the renal glomerulus, where traces were visible at 8 days. In mice injected with streptococcal culture intraperitoneally, M protein was detected at sites of focal abscesses in liver and spleen, and on the serous surfaces of these organs. The histologic distribution of M protein is compared with that described previously for pneumococcal polysaccharide and animal protein. Differences in the extent of distribution and in the characteristics of antigen deposition are pointed out.
Nonsurgical Palliation of Congenital Heart Malformations
Authors: Peter M. Olley
Journal: New England Journal of Medicine (1975)

From time to time nonsurgical technics have been proposed for the treatment or palliation of certain congenital heart defects. These have included a modified cardiac catheter used to relieve pulmonary and tricuspid-valve stenosis,1 catheter closure of persistent ductus arteriosus,2 and tissue-adhesive closure of aortic-pulmonary communications.3 Although none of these procedures have been widely accepted, the technic of Miller and Rashkind for creating an atrial septal defect by use of a balloon-tipped catheter4 has become established as the initial emergency treatment of patients with transposed great arteries when mixing between the systemic and pulmonary circulations is crucial to survival. The special . . .
Multidrug resistance after inappropriate tuberculosis treatment: a meta-analysis
Authors: Marieke J. van der Werf, Miranda W. Langendam, Emma Huitric, Davide Manissero
Journal: European Respiratory Journal (2011)

We conducted a systematic review and meta-analysis to assess the evidence for the postulation that inappropriate tuberculosis (TB) regimens are a risk for development of multidrug-resistant (MDR)-TB. MEDLINE, EMBASE and other databases were searched for relevant articles in January 2011. Cohort studies including TB patients who received treatment were selected and data on treatment regimen, drug susceptibility testing results and genotyping results before treatment and at failure or relapse were abstracted from the articles. Four studies were included in the systematic review and two were included in the meta-analysis. In these two studies the risk of developing MDR-TB in patients who failed treatment and used an inappropriate treatment regimen was increased 27-fold (RR 26.7, 95% CI 5.0–141.7) when compared with individuals who received an appropriate treatment regimen. This review provides evidence that supports the general opinion that the development of MDR-TB can be caused by inadequate treatment, given the drug susceptibility pattern of the Mycobacterium tuberculosis bacilli. It should be noted that only two studies provided data for the meta-analysis. The information can be used to advocate for adequate treatment for patients based on drug resistance profiles.
Ataxia-Telangiectasia and Swiss-Type Agammaglobulinemia
Authors: Victor A. McKusick
Journal: JAMA (1966)

In 1941 Louis-Bar<sup>41</sup>described an isolated case of progressive cerebellar ataxia associated with oculocutaneous telangiectasia. This syndrome became well known with the publication of eight cases of Boder and Sedgwick<sup>12</sup>in 1958. The latter authors gave the name ataxia-telangiectasia (AT) and added the third major component of the syndrome, recurrent severe sinopulmonary infection. They also emphasized the familial nature of the disease. The neurological manifestations of AT are usually the first to appear. Abnormalities are often detectable when the child begins to walk or even earlier. Two features, in addition to progressive cerebellar signs, are characteristic of the neurological picture: (1) choreic and athetoid movements were responsible for the title chosen by Wells and Shy<sup>75</sup>for their report in 1957: "Progressive familial choreoathetosis with cutaneous telangiectasia," and (2) pseudopalsy of the eyes which has been likened to oculomotor apraxia is present in most cases.<sup>66</sup>The patient is
Book on Uric Acid.
Authors: J. B. Nichols
Journal: JAMA (1905)

Washington, D. C., May 13, 1905. <h3>To the Editor:</h3> —Referring to the announcement on page 1547 ofThe Journalof May 13. as to republication of the series of articles on immunity, permit me to express the hope that the series of valuable papers on uric acid will also be republished in book form and under the author's name. <h3>[Editor's Note:</h3> The editorials on "Truth and Poetry of Uric Acid," slightly enlarged, will be reprinted in book form with the author's name.]
Effects of Beta Blockade on the Peripheral Manifestations of Thyrotoxicosis
Authors: WILLIAM GROSSMAN
Journal: Annals of Internal Medicine (1971)

A double-blind controlled study was conducted in 10 patients to determine the effects of beta adrenergic blockade with sotalol on the peripheral manifestations of thyrotoxicosis. After sotalol administration prompt and significant decreases were noted in tremor frequency (8.2 ± 0.4 cps to 7.1 ± 0.4 cps, P < 0.01), stare (22.9 ± 1.4 mm to 19.7 ± 1.3 mm, P < 0.01), lid-lag (decreased in three of four patients), and globe-lag (decreased in all of three patients). A decrease in hyperreflexia after beta adrenergic blockade was documented by prolongation of the ankle jerk T½ (235 ± 12 msec to 271 ± 16 msec, P < 0.01) as measured with a photomotogram. Definite subjective improvement was reported by six patients after sotalol but by only one patient after saline administration. No significant changes occurred in exophthalmos or serum thyroxine levels after sotalol, and only minimal changes were noted in tremor amplitude (3.64 ± 0.7 to 2.94 ± 0.5, 0.05 < P < 0.1). It is concluded that the tremor, stare, hyperreflexia, lid-lag, and globe-lag of thyrotoxicosis are mediated by the beta adrenergic nervous system. Important physiologic considerations, however, suggest that caution be exercised in the use of beta adrenergic blockade over prolonged periods in patients with thyrotoxicosis.
IL-4 instructs TH1 responses and resistance to Leishmania major in susceptible BALB/c mice
Authors: Tilo Biedermann, Stephan Zimmermann, Hayo Himmelrich, Alain Gumy, Oliver Egeter, Arne K. Sakrauski, Irene Seegmüller, Heike Voigt, Pascal Launois, Alan D. Levine, Hermann Wagner, Klaus Heeg, Jacques A. Louis, Martin Röcken
Journal: Nature Immunology (2001)
Gene Therapy: The Need for Basic Science
Authors: Inder M. Verma
Journal: Molecular Therapy (2000)

Fifteen years ago I made a slide to highlight the hurdles to be cleared before gene therapy could become a successful enterprise. These were (1) vectorology (delivery systems), (2) molecular biology (expression and regulation), (3) immunology (antibodies, tolerance), and (4) cell biology (transplantation, stem cells). I end most of my talks with this slide (despite its being black and white), often pleading with the students and postdoctoral fellows to pursue the basic science of gene therapy. We have made extensive progress in each area but, surprisingly, these hurdles are still the bane of gene therapy.
Overpopulation and overconsumption.
Authors: R Smith
Journal: BMJ (1993)

smoking cessation centres, with success rates much the same as those obtained with nicotine chewing gum." 18 In hospital patients with smoking related diseases transdermal nicotine seems to confer little if any benefit over advice and support alone.Its value has yet to be proved when it is bought over the counter and used without any professional advice and support.The question of whether using both transdermal nicotine and nicotine chewing gum might improve cessation rates is worth answering, especially in heavy smokers.
Heatstroke induces liver injury via IL-1β and HMGB1-induced pyroptosis
Authors: Yan Geng, Qiang Ma, Ya-Nan Liu, Na Peng, Fang-Fang Yuan, Xing-Gui Li, Ming Li, Ying-Song Wu, Bing-ling Li, Wei-bing Song, Wei Zhu, Wei-Wen Xu, Jie Fan, Lei Su
Journal: Journal of Hepatology (2015)
275. Immunostimulatory Antigen Loaded Microparticles as Cancer Vaccines
Authors: Aliasger K. Salem, Anthony D. Sandler, George J. Weiner, Xueqing Zhang, Nicki K. Baman, Xiaoyan Zhu, Christopher E. Dahle
Journal: Molecular Therapy (2006)

The incidence rate for melanoma since 1973 has more than doubled from 5.7 to 14.31 per 100,000. A significant portion of these patients were not cured by chemotherapy or radiation treatment following resection. Immunotherapeutic treatments that utilize ligands for Toll like receptors (TLRs) has significant potential to treat melanoma. We have demonstrated that we can prepare degradable polymer particles with TLR ligands such as cytosine-phosphorothioate- guanine oligodeoxynucleotide (CpG ODN) motifs entrapped within them and provide functional delivery. We have shown that these microparticles are effeciently taken up by antigen presenting cells (APCs) such as dendritic cells (DCs). We have also shown that the CpG ODN ligands which bind to intracellular TLR9 produce significantly stronger CD8+ responses when they are delivered in biodegradable microparticles in comparison to delivery of CpG ODN in solution. Delivery of the CpG ODN ligands in our microparticle vaccine did not upregulate immunosuppressive molecules and acted as a strong immunotherapeutic treatment in a murine melanoma model.