tbuckley/cabot-search huggingface dataset:
Doctors with health problems should seek help
Authors: L. Beecham
Journal: BMJ (1998)

<h3>Introduction</h3> Erythropoietin (EPO) is a commonly used option in the treatment of chemotherapy-induced anaemia (CIA). However, ∼30–50% of patients fail to achieve an adequate response after initial treatment. Prior studies have demonstrated that intravenous iron might synergistically improve therapeutic response to EPO treatment in this patient population. <h3>Methods and analysis</h3> We will perform this multicentre, randomised, open-label, parallel-group, active controlled non-inferiority study to compare the two combination therapies of EPO plus intravenous iron regimen versus doubling the dose of EPO in patients with CIA who have an inadequate response to initial EPO treatment at a routine dose. A total of 603 patients with an increase in haemoglobin (Hb) &lt;1 g/dL will be enrolled and randomised to one of the three study treatment groups at a 1:1:1 ratio <i>Group 1</i>: EPO treatment at the original dose plus intravenous iron dextran 200 mg every 3 weeks (Q3W) for 15 weeks; <i>Group 2</i>: EPO treatment at the original dose plus intravenous iron dextran 100 mg, twice a week for 5 weeks; <i>Group 3</i>: the control group, doubling the EPO dose without preplanned iron supplementation. The primary outcome measure to compare is the Hb response rate at week 15 and the secondary end points involve therapeutic blood transfusions. Time-to-progression, adverse events and quality of life will also be evaluated. <h3>Ethics and dissemination</h3> All participants will provide informed consent; the study protocol has been approved by the independent ethics committee of Shanghai East Hospital. This study would clearly demonstrate the potential benefit of combining epoetin treatment with intravenous iron supplementation. Findings will be shared with participating hospitals, policymakers and the academic community to promote the clinical management of CIA in China. <h3>Trial registration number</h3> NCT02731378.
MYOCARDIAL INFARCTION
Authors: Oscar L. McFadyen
Journal: JAMA (1960)

A 17-year-old man presented himself at the emergency room of Cape Fear Valley Hospital on the evening of Sept. 20, 1959, complaining chiefly of severe chest pain of one and one-half hours' duration. The patient was in good health until the night prior to admission to the hospital, when he had an episode of transient nausea and vomiting unaccompanied by pain. On the day of admission, about 30 minutes after eating a large evening meal, the patient began having severe substernal chest pain which did not radiate. He became nauseated and vomited once on the way to the hospital. The chest pain continued for one and one-half hours, until the patient was seen at Cape Fear Valley Hospital. At that time he complained of numbness in his arms. There was no radiation of the pain into the jaw, the arms, or the back. The patient's father, who was 50 years
Rwanda launches vaccination drive against pneumococcal disease in under 5s
Authors: P. Moszynski
Journal: BMJ (2009)

This week Rwanda launched a national drive to combat pneumococcal disease, the leading vaccine preventable killer of children under 5 worldwide. The drive is thought to be one of the developing world’s first national immunisation programmes against a disease that causes life threatening illnesses, such as pneumonia, meningitis, and sepsis, and might have a substantial effect on mortality in children under 5.

The programme is a joint effort by the Rwandan government and the Global Alliance for Vaccines and Immunization (GAVI), a partnership that includes the World Health Oorganization, Unicef, and the World Bank, funded by donor countries and the Bill & Melinda Gates Foundation, and the Pneumococcal Accelerated Development and Introduction Plan …
Thomas Beddoes, M.D., and the Pneumatic Institution at Clifton, 1798-1801
Authors: LEON S. GOTTLIEB
Journal: Annals of Internal Medicine (1965)

Medical History1 September 1965Thomas Beddoes, M.D., and the Pneumatic Institution at Clifton, 1798-1801LEON S. GOTTLIEB, M.D.LEON S. GOTTLIEB, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-63-3-530 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptToward the close of the eighteenth century, the discovery of oxygen and other gases induced enthusiasts to anticipate favorable results in pulmonary disease from the inhalation of various gases. Outstanding among the early investigators exploring this new mode of therapy was Thomas Beddoes, of Bristol, England. Beddoes envisioned for the treatment of lung ailments the founding of a Pneumatic Institution that would consist of a hospital, clinic, and a scientific laboratory for the investigation of "factitious airs." Materially implemented by philanthropic friends, Beddoes' plans were finally realized, and at Clifton, overlooking the town of Bristol, the Pneumatic Institution was established....References1. STOCK JE: Memoirs of the Life of Thomas Beddoes, M.D. John Murray, London, 1811. Google Scholar2. DAVY J: The Life of Sir Humphry Davy, Bart. Longman, Rees, Orme, Brown, Green, and Longman, London, 1836. Google Scholar3. THORPE TE: Humphry Davy—Poet and Philosopher. Cassel and Co., London, 1896. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: LEON S. GOTTLIEB, M.D.Affiliations: Los Angeles, CaliforniaFrom the Pulmonary Department, Memorial Hospital of Southern California, Culver City, Calif.Requests for reprints should be addressed to Leon S. Gottlieb, M.D., 10921 Wilshire Blvd., Los Angeles, Calif. 90024. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byFamily and Reputation 1 September 1965Volume 63, Issue 3Page: 530-533KeywordsHospitalsInhalationLungsOxygenPulmonary diseasesResearch laboratoriesRespiratory system procedures ePublished: 1 December 2008 Issue Published: 1 September 1965 PDF downloadLoading ...
Falsification of Clinical Credentials by Physicians Applying for Ambulatory-Staff Privileges
Authors: William A. Schaffer, F. David Rollo, Carol A. Holt
Journal: New England Journal of Medicine (1988)

Abstract As part of a quality-assurance program, we reviewed the clinical credentials listed on applications from 773 physicians applying for clinical positions in the Humana MedFirst national ambulatory care program between March 1 and December 31, 1986. In 39 applications (5.0 percent), physicians presented false clinical credentials: 27 physicians (3.5 percent) gave false information about their residency, 10 (1.3 percent) falsely reported board certification, and 2 (0.3 percent) provided false information about both residency and board certification. There was no significant difference between the falsification rates among graduates of U.S. medical schools and those among graduates of foreign medical schools, or among those in the various medical specialties. Falsification was more common among physicians recruited locally than among those recruited nationally, and was significantly more common among applicants who graduated before 1970. Because this sample included only applicants for ambulatory privileges within a single organization, the findings may be of uncertain generalizability to groups of physicians applying for other classes of privileges in other institutions. We conclude that in applying for some clinical privileges, physicians present inaccurate clinical credentials more frequently than might be expected. (N Engl J Med 1988; 318:356–8.)
Evolution of the AT-rich mitochondrial DNA of the root knot nematode, Meloidogyne hapla
Authors: A. Hugall, J. Stanton, C. Moritz
Journal: Molecular Biology and Evolution (1997)

Mitochondrial DNA of the root knot nematode Meloidogyne hapla was investigated for intraspecific diversity and divergence from other parthenogenetic root knot nematodes. A 1,900-bp fragment containing COII, tRNAHis, 16S rRNA, ND3 and Cyt b genes has been cloned and sequenced from one individual and an 1,188-bp region within this region was sequenced from four other Australian isolates. M. hapla mtDNA is more than 80% AT-rich, like other Meloidogyne spp. Nucleotide diversity within M. hapla is some 10-fold higher than across three other parthenogenetic species of root-knot nematode (M. arenaria, M. javanica, and M. incognita), implying an earlier origin for M. hapla. Nucleotide divergence between M. hapla and its congener M. javanica is as great as that between Ascaris suum and Caenorhabditis elegans, members of different nematode subclasses, while amino acid sequence difference between Meloidogyne is more than twice as great. This is interpreted as an AT-bias-induced acceleration of the amino acid substitution rate, over and above saturation of nucleotide divergence in the strongly AT-biased DNA, on three lines of evidence: (1) in conserved blocks in 16S rDNA congeneric Meloidogyne have no more differences than between A. suum and C. elegans; (2) the Meloidogyne lineage has more amino acid changes relative to the Ascaris/Caenorhabditis lineage with respect to four of five outgroups, the exceptional outgroup being the only species (Apis) as AT-rich as Meloidogyne; and (3) between the two Meloidogyne there are more first and second but fewer third codon position changes than between the other nematode species. M. hapla is also found to contain a 102-bp tandem repeat of at least 40 copies; a size, arrangement, and position the same as in M. javanica, but sequence comparisons did not demonstrate homology between the two repeats.
Influence of Ventilator Settings in Determining Respiratory Frequency during Mechanical Ventilation
Authors: FRANCO LAGHI, KISHORE KARAMCHANDANI, MARTIN J. TOBIN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

During mechanical ventilation, changes in inspiratory flow and tidal volume (VT) have been shown to alter respiratory frequency (f ). However, the changes in flow and VT have been accompanied by alteration in ventilator inspiratory time (TI,(vent)), and it is not clear which variable is the primary determinant. To address this issue, we employed four protocols in 15 healthy volunteers receiving assist-control ventilation. When VT was fixed and flow was delivered at 30, 60, and 90 L/min, f increased as a function of the increase in flow and the decrease in TI,(vent). When flow was held constant and VT was changed among 0.5, 1.0, and 1.5 L, f increased as a function of the decreases in VT and TI,(vent). When flow was increased from 60 to 90 L/min and these changes were balanced with VT settings of 1.0 and 1.5 L to maintain a constant TI,(vent), f did not change. When flow and VT were held constant and TI,(vent) was varied by the application of inspiratory pauses (0 to 2 s), f decreased as a function of the increase in TI,(vent) (p < 0.001). In conclusion, the imposed ventilator inspiratory time during mechanical ventilation can determine f independently of delivered inspiratory flow and VT.
OPERATIVE VS. NONOPERATIVE PROCEDURES FOR UTERINE FIBROIDS
Authors: ROBERT T. FRANK
Journal: JAMA (1949)

Every week day for almost fifty years I have been seeing, examining and advising women who are sick or believe themselves to be sick. A large number are fear stricken and panicky. Some hide it because of pride, upbringing and convention; others show naked fear unashamed. Their fear is of invalidism, pain, tumor, cancer and death. They may have watched a sick member of their family fade away, listened to gruesome gossip from a neighbor and, to culminate it all, have been told tactlessly by their physician that they have a tumor in the breast, womb or ovary which requires immediate operation. The impression made by this or analogous combinations of events causes a fixation which may resist all attempts to convince them that the condition is harmless, nonmalignant, and does not require operation. Today, the widely publicized cancer campaigns, the insistence of the public itself on the routine making
Abstract 4762: Genistein and Indole 3 carbinol induced apoptosis in endometrial cancer cell through DR5 mediated pathway
Authors: Chi-Heum Cho, So-Jin Shin, Sang-Hoon Kwon, Soon-Do Cha, Yong-Man Kim
Journal: Cancer Research (2011)

Abstract Objective: To address the growth inhibitory effects of Genistein and Indole 3 carbinol in endometrial cancer cell growth and evaluate its effect on apoptosis using ishikawa endometrial cancer cell line. Methods: Human endometrial cancer cells ishikawa were cultured and treated with various concentrations of Genistein and Indole 3 carbinol alone and in combination. Cell proliferation and growth arrest were evaluated by MTS assay and FACS analysis, respectively. The apoptosis induced was analyzed by DNA fragmentation and western blotting. Results: Combination of Genistein and Indole 3 carbinol significantly inhibited the proliferation of ishikawa cells in dose dependent manner. Cell cycle analysis indicated the increased proportion of cell arrest in sub G1 phase. DNA fragmentation, up regulation of DR5, down regulation of c-Flip, cleavage of caspase-8 and PARP revealed apoptotic progression. Conclusion: Genistein and Indole 3 carbinol synergistically inhibited the growth of endometrial cancer cell. Significant induction of apoptosis is associated with DR5 regulated death dependent pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4762. doi:10.1158/1538-7445.AM2011-4762
Activated Ras Signals Developmental Progression of Recombinase-activating Gene (RAG)-deficient Pro-B Lymphocytes
Authors: Albert C. Shaw, Wojciech Swat, Roger Ferrini, Laurie Davidson, Frederick W. Alt
Journal: The Journal of Experimental Medicine (1999)

To elucidate the intracellular pathways that mediate early B cell development, we directed expression of activated Ras to the B cell lineage in the context of the recombination-activating gene 1 (RAG1)-deficient background (referred to as Ras–RAG). Similar to the effects of an immunoglobulin (Ig) μ heavy chain (HC) transgene, activated Ras caused progression of RAG1–deficient progenitor (pro)-B cells to cells that shared many characteristics with precursor (pre)-B cells, including downregulation of surface CD43 expression plus expression of λ5, RAG2, and germline κ locus transcripts. However, these Ras–RAG pre-B cells also upregulated surface markers characteristic of more mature B cell stages and populated peripheral lymphoid tissues, with an overall phenotype reminiscent of B lineage cells generated in a RAG- deficient background as a result of expression of an Ig μ HC together with a Bcl-2 transgene. Taken together, these findings suggest that activated Ras signaling in pro-B cells induces developmental progression by activating both differentiation and survival signals.
The Physical Exam and the Sense of Smell
Authors: Andrew Bomback
Journal: New England Journal of Medicine (2006)

Throughout medical school, I heard one attending physician after another bemoan the death of the physical examination. "I can read the echo report myself," a cardiologist once chided me when I detailed the specifics of a patient's tricuspid regurgitation-jet velocity, "but right now I'd like to know what you heard with your stethoscope." On another occasion, I spent a grueling half hour by the bedside, struggling to answer endless questions from a rheumatologist about a patient's fingernails. During a month with the endocrinology team, I was assigned to simulate hypocalcemia, faking facial twitches and carpal spasms, as my fellow medical . . .
Abstract 462: Soluble CD80 restores T-cell activation and overcomes tumor cell programmed death ligand-1-mediated suppression.
Authors: Samuel Haile, Sonia P. Dalal, Virginia Clements, Koji Tamada, Suzanne Ostrand-Rosenberg
Journal: Cancer Research (2013)

Abstract Many tumor cells escape anti-tumor immunity through their expression of Programmed Death Ligand 1 (PDL1 or B7-H1), which interacts with T cell-expressed PD1 and results in T cell apoptosis. We previously reported that transfection of human tumor cells with a membrane-bound form of the costimulatory molecule CD80 prevented PD1 binding and restored T cell activation. We now report that membrane-bound CD80 similarly reduces PDL1-PD1-mediated suppression by mouse tumor cells, and that a fusion protein consisting of the extracellular domains of CD80 fused to an Fc domain of IgG1 overcomes PDL1-mediated suppression by human tumor cells. T cell activation experiments assessing costimulation indicate that the soluble CD80 fusion protein mediates its effects by binding to PDL1 and inhibiting PDL1-PD1 interactions. Comparison of the CD80 fusion protein to antibodies specific for PD1 or PDL1 demonstrate that soluble CD80 treatment is more effective in restoring T cell activation than treatment with mAb to either PD1 or PDL1. These studies identify soluble CD80 as an alternative and potentially more efficacious therapeutic agent for overcoming PDL1-induced immune suppression and facilitating tumor-specific immunity. Citation Format: Samuel Haile, Sonia P. Dalal, Virginia Clements, Koji Tamada, Suzanne Ostrand-Rosenberg. Soluble CD80 restores T-cell activation and overcomes tumor cell programmed death ligand-1-mediated suppression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 462. doi:10.1158/1538-7445.AM2013-462
True Leukonychia in Crohn Disease Induced by Selenium Deficiency
Authors: Naoko Hasunuma, Yoshihiro Umebayashi, Motomu Manabe
Journal: JAMA Dermatology (2014)

Leukonychia is divided into 2 major types: true leukonychia, which involves the nail plate, and apparent leukonychia, which involves the nail bed.1 Herein, we present the first case to our knowledge of true leukonychia successfully treated with selenium substitution.
Agranulocytosis Associated with Antithyroid Drugs
Authors: D. S. Cooper, D. Goldminz, A. A. Levin, P. W. Ladenson, G. H. Daniels, M. E. Molitch, E. C. Ridgway
Journal: Annals of Internal Medicine (1983)

The records of all patients with antithyroid drug-related agranulocytosis at two Boston hospitals (Group 1, 14 patients), as well as the published case reports of 36 patients with this syndrome (Group 2) were reviewed. The clinical characteristics of these patients were then compared with those of 50 hyperthyroid patients who had taken antithyroid medication without untoward hematologic reactions (Group 3). The mean ages of patients in Group 1 and Group 2 were significantly greater than that of Group 3 (50.6 ± 16 years versus 35.7 ± 13.7 years, p < 0.001; 46.3 ± 18.7 years versus 35.7 ± 13.7 years, p < 0.02). By chi-squared analysis, the relative risk of developing agranulocytosis in patients over age 40 was 6.4 times that among younger patients (p < 0.001). The mean doses of methimazole in Group 1 and Group 2 were significantly higher than that in Group 3 (43.8 ± 9.9 mg/d versus 29.5 ± 10.4 mg/d, p < 0.001; 40.7 ± 15.7 mg/d versus 29.5 ± 10.4 mg/d, p < 0.02), with an 8.6-fold increased risk of agranulocytosis with doses greater than 40 mg/d (p < 0.01). In contrast, the mean doses of propylthiouracil did not differ among the three groups. These data suggest that antithyroid drugs should be administered cautiously to patients over age 40. Because no cases of agranulocytosis were seen with methimazole doses less than 30 mg/d, low-dose methimazole therapy may be safer than high-dose therapy or treatment with conventional doses of propylthiouracil.
Abstract 2872: Induction of autophagy in hypoxic HT29 cells requires functional JNK1
Authors: Irina A. Vasilevskaya, David Roberts, Peter J O'Dwyer
Journal: Cancer Research (2011)

Abstract BACKGROUND: Hypoxic HT29 colon cancer cell lines exhibit higher sensitivity to oxaliplatin when SEK1 function is impaired and higher resistance when MKK7 is down regulated (which in turn, cause more profound inhibition of JNK activation). We observed differential effects of JNK1/JNK2 modulation on oxaliplatin sensitivity of hypoxic HT29 cells to oxaliplatin treatment that implied a pro-survival function for JNK1. Further, we have shown that both oxaliplatin- and hypoxia-induced autophagy in these cells is diminished in the presence of JNK inhibitor SP600125, and that the cells are sensitized thereby. PURPOSE: Here we investigate further how modulation of signaling through JNK influences autophagy in hypoxic HT29 cells treated with oxaliplatin, and expand the cellular model to additional colon cancer cell lines. We created a panel of HT29-derived cell lines stably expressing dominant negative constructs for SEK1 (HTS13), MKK7 (HTM9), JNK1 (HTJ1.3) and JNK2 (HTJ2.2). We also utilized 6 colon cancer cell lines (HCT116, LoVo, RKO1, SW480, DLD1 and HCT15) in which a dominant negative construct for JNK1 was introduced by viral delivery. RESULTS: Our data demonstrate that in HTJ1.3 cells, hypoxic induction of autophagy is impaired. Silencing of JNK2 in these cells by viral delivery of shRNA does not affect either autophagy induction, or sensitivity to oxaliplatin. Downregulation of up-stream activators of JNK, as in the dnSEK1 or dnMKK7 derivatives, similarly does not affect autophagy induction, while still demonstrating differential effects on activation of JNK isoforms and its major target, c-Jun. Finally, we show that colon cancer cell lines differ in their ability initiate autophagy under hypoxia. Correspondingly, the introduction of dominant negative JNK1 causes some enhancement of oxaliplatin cytotoxicity in LoVo, RKO1 and HCT15 cell lines, which all demonstrate a greater propensity to autophagy under these circumstances. CONCLUSIONS: Our data demonstrate that JNK1 plays a central role in autophagy induction under hypoxic conditions. Knockdown of JNK1 renders HT29 cells more sensitive to hypoxia due to impaired autophagy induction, and JNK2 is unable to substitute for JNK1 under these conditions. Our results also imply involvement of alternative JNK1 activators in autophagy induction by hypoxia. Finally, induction of autophagy and enhancement of oxaliplatin cytotoxicity, by this mechanism, appear to be model-specific in colon cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2872. doi:10.1158/1538-7445.AM2011-2872