tbuckley/cabot-search huggingface dataset:
Efficacy and Toxicity of Sodium Stibogluconate for Mucosal Leishmaniasis
Authors: Eileen D. Franke
Journal: Annals of Internal Medicine (1990)

To determine the efficacy and toxicity of the World Health Organization's (WHO) recommended treatment for mucosal leishmaniasis: antimony, 20 mg/kg body weight per day for 28 days.Open trial with 12-month follow-up.Inpatient unit of a regional referral hospital in a developing country.Twenty-nine consecutive eligible patients with culture-confirmed infection of the mucosa with Leishmania species who were otherwise healthy. Eight patients (28%) had mild to moderate disease (confined to the nasal mucosa). Twenty-one patients (72%) had severe disease (including the oropharynx as well as the nasal mucosa).Antimony, 20 mg/kg body weight intravenously every day for 28 days. Patients received antimony in the form of sodium stibogluconate.Initial results of therapy were as follows: 63 of 72 lesions (88%) healed or markedly improved; all lesions were culture-negative for parasites; and 18 of 29 patients (62%) showed complete clinical and parasitologic cure of all lesions. By the 12-month follow-up examinations, however, 37 lesions had recurred, 8 new lesions had appeared, and only 8 patients (30%) showed clinical cure of all lesions. Of the 8 patients with mild to moderate disease, 6 were cured compared with only 2 of the 21 patients with severe disease. Side effects of this treatment regimen included T-wave inversion on electrocardiogram (4 patients), abnormal liver function tests (10 patients), and musculoskeletal pain (24 patients). No side effects occurred during week 1 of therapy.The only recommended treatment for mucosal leishmaniasis is ineffective in patients with severe disease. The acceptable toxicity of the regimen suggests that longer courses of therapy with antimony, or that trials with other antileishmanial agents alone or combined with antimony be evaluated as initial therapy for this disease.
Band 3 peptides inhibit deoxy S polymerization: Viscosity studies
Authors: Elizabeth H. Danish, David W. Lundgren, John W. Harris
Journal: American Journal of Hematology (1993)

Abstract We have previously obtained evidence that N‐terminal band 3 peptides inhibited deoxyhemoglobin S (deoxy S) polymerization as determined by equilibrium solubility assays. An N:1‐15AA fragment binds to the 2,3‐diphosphoglycerate (2,3‐DPG) receptor locus of deoxy S with five to seven amino acids (AA) extending internally, while ten to eight AA remained external to deoxy S and inhibited polymerization by steric hindrance. A true mirror‐image peptide, corresponding to two N:1‐8AA + lysine (K) linked by coupler, binds to the 2,3‐DPG loci of two deoxy S molecules, tethering them together to form “binary complexes” incapable of entering the polymer chains. The reduction in the concentration of deoxy S available for extended chain formation decreased polymerization. We now report time:viscosity profiles of the sol‐gel transformation of purified solutions of deoxy S with and without peptides and studies of the gel solidity at equilibrium. Samples with peptides had longer lag times than controls of similar deoxy S concentrations. The mirror‐image peptide was a more effective inhibitor than the N:1‐15AA peptide. When the mirror‐image peptide was present in peptide:hemoglobin molar ratios of 0.25‐1:1, the increases in lag time were equivalent to decreasing the deoxy S concentrations by 15–25%, comparable to projected major therapeutic effects. Gel solidity, determined by yield temperature, was less in the sample with mirror‐image peptide compared to control. These results support the proposed mechanisms of inhibition of deoxy S polymerization by band 3 peptides. © 1993 Wiley‐Liss, Inc.
Abstract 2378: Involvement of leptin-activated canonic and non-canonic kinases in VEGF regulation in breast cancer
Authors: Yanbo Xu, Amber Watters, Yuanyuan Zhang, Corey Gillespie, Weiqiang Zhou, Shanchun Guo, Samuel J. Leibovich, Ruben Rene Gonzalez-Perez
Journal: Cancer Research (2010)

Abstract We have previously reported that in vitro and in vivo leptin signaling up-regulates VEGF in mouse and human mammary tumor cells (MT) but the specific molecular mechanisms involved are largely unknown. Here we describe how leptin activated canonic and non-canonic signaling pathways to induce specific transcription factors (TF) essential for the transcriptional activation of VEGF gene in mouse MT (4T1, EMT6 and MMT). Basal expression of VEGF/VEGFR2, leptin/OB-R and ER-α was initially investigated in MT. Leptin dose-response and time-course effects on VEGF levels were determined by ELISA. Several pharmacological inhibitors for key leptin-target kinases and TF were used to dissect the signaling pathways involved in leptin-induced levels of VEGF protein and mRNA in MT. A series of VEGF-promoter Luc-reporters [full-length &amp; transcription factor (TF)-binding deletions: HRE, AP1, AP2, NFκB and SP1] were transfected into MT to analyze leptin regulation of VEGF transcription. Our data show that MAPK, PI-3K (canonic) and PKC, JNK and p38 MAP kinase (non-canonic) signaling pathways were generally involved in leptin regulation of VEGF. Analysis of cis-acting elements of VEGF promoter shows that leptin activation of HIF-1α is essential for transcription in all MT. This was mainly linked to MAPK, PI-3K, PKC, JNK and p38 signaling. Leptin-induced MAPK, JNK and p38 to activate NFκB that was essential for VEGF expression in high producer MT (EMT6 and MMT). Leptin through all canonic signaling pathways activates SP1 required for VEGF regulation in 4T1 cells. In contrast, AP1 was not involved but AP2 repressed leptin-mediated transcription of VEGF. Overall, these data suggest that leptin signaling regulates VEGF gene in MT cells mainly through HIF-1α and NFκB. These results delineate for first time the mechanisms for leptin regulation of VEGF and, reinforce the idea that the disruption of leptin signaling could impact breast cancer growth by inhibiting MT proliferation and angiogenesis. This work was supported in part by NIH/NCI 1SC1CA138658-02; NIH/UAB Breast SPORE Career Development Award; BC 504370 Susan G. Komen Foundation for the Cure and the Georgia Cancer Coalition Distinguished Cancer Scholar Award (to RRGP). 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 2378.
Overdosage Effects and Danger from Tranquilizing Drugs
Authors: Charles H. McKown
Journal: JAMA (1963)

Over a 17-month period 968 cases of tranquilizer ingestion reported to the National Clearinghouse for Poison Control Centers were reviewed for tranquilizer toxicity and side effects. Anticipated pharmacological actions were correlated with symptomatology, etiology, and age of patients involved. Of 378 patients who ingested phenothiazine derivatives, 113 revealed CNS depression, 90 ingested the tranquilizer intentionally, and 254 were less than 13 years of age. The corresponding figures for 151 cases of Rauwolfia alkaloid ingestion were 25, 4, and 142, respectively; for 280 cases of substituted diol ingestion, 135, 166, and 63, respectively, and for 115 cases involving drugs of miscellaneous structure, 36, 49, and 57, respectively. The clinician's attention is called to the frequency of CNS depression after tranquilizer ingestion and the high incidence of suicide attempts with the less potent tranquilizers.
Immune responses to <i>Aspergillus</i> antigen in IL‐4‐/‐ mice and the effect of eosinophil ablation
Authors: VP Kurup, PS Murali, J‐Q Xia, JN Fink, HY Choi, RL Coffman
Journal: Allergy (1999)

Background : Exposure to Aspergillus fumigatus allergens results in enhanced total serum IgE and peripheral blood eosinophils in mice. The associated pulmonary inflammation and immunologic responses are comparable to those detected in human allergic bronchopulmonary aspergillosis. Allergen‐induced cytokines are thought to regulate the inflammatory and immune responses in these animals. Methods : In the present study, we exposed C57BL/6 and BALB/c mice to A. fumigatus antigen. Both wild‐type and IL‐4 knockout phenotypes of animals of both strains were used. Some animals were also treated with anti‐IL‐5 or anti‐IFN‐γ. Total serum IgE, Aspergillus species IgG subclass, peripheral blood eosinophils, and lung histology were studied. Results : The results demonstrate similar lung inflammation in all wild‐type and IL‐4‐/‐ animals exposed to A. fumigatus antigen. Similarly, in spite of the diverse immune response produced by the anticytokine treatment, no major differences were detected among any of the animal groups studied. Conclusions : It can be concluded that A. fumigatus exposure in an immunologically unaltered host is predominantly of a Th2 type, and that depletion of the Th2 cytokine leads to a similar lung inflammation but with a characteristic Th1 response, suggesting that the pathogenesis of allergic aspergillosis is the result of multiple induction pathways.
An End to Patchwork Reform of Health Care
Authors: R L Dickman, A B Ford, J Liebman, S Milligan, A L Schorr
Journal: New England Journal of Medicine (1987)

Our system of health care may be said to be one of the longest-lived, most expensive demonstration projects in history — a test of the efficacy of "free-market" health care. The time has come to step back and evaluate the project. We conclude that although superb care has been delivered to some persons in some places, the free-market system has never delivered good health care to everyone at a reasonable cost. Although the Hill–Burton Act, Medicare, Medicaid, health maintenance organizations (HMOs), and other partial measures have improved access to health care, the system during the past few years has shown . . .
Gas Gangrene Following an Intramuscular Injection of Concentrated Liver Extract
Authors: Edward S. Brewster
Journal: JAMA (1962)

THE APPEARANCE of gas gangrene at sites of parenteral injections is truly unique. A careful survey of world medical literature reveals that a total of 117 instances of gas gangrene from parenteral injections has been reported to date. An initial series of 83 cases was first assembled in 1936 by Touraine, who gathered the cases from France, Germany, and Italy. A second series, comprising 30 additional cases was reported from Brazil, in 1951. Great Britain contributed 2 more cases during 1946 and 1956 respectively, and Australia reported 1 case in 1957. No record of any instance of gas gangrene from a parenteral injection has appeared in American medical literature prior to the recent case by Koons and Boyden, published during January, 1961.  Herewith, is presented what is believed to be the second case of gas gangrene following parenteral injection to be reported in the United States, despite the fact that
OP33 * GLYCOGEN SYNTHASE KINASE INHIBITORS REDUCE 3D MIGRATION OF PATIENT DERIVED GLIOBLASTOMA MULTIFORME STEM CELLS
Authors: D. M. Tams, C. Murray, S. T. Barry, S. Lawler, A. Bruning-Richardson, S. Short
Journal: Neuro-Oncology (2014)

INTRODUCTION: Glioblastoma multiforme (GBM) is a fast growing, highly invasive malignant brain tumour. Inhibition of tumour cell migration into normal brain tissue represents a major target for treatment. Glycogen synthase kinase (GSK-3) inhibition has been associated with reduced GBM invasion in in vitro and in vivo models. Targeting this pathway with established and/or novel drugs may elucidate more effective treatment combinations. METHOD: The effect of GSK-3 inhibitors BIO, AZD2858, AZ1293 and AZ1080 on GBM migration was assessed in patient derived GBM stem cells (GBM-1) and two established cell lines (U251 and U87) using a 3D collagen based assay. Multiple drug concentrations were investigated with up to 72 hours exposure. A migration index was determined using aggregate core size and cell migration area. Immunohistochemistry and immunocytochemistry were used to assess cell morphology and cytoskeletal changes. RESULTS: All compounds inhibit migration in this model. AZD2858 was the most potent, causing significant effects at 1 micro molar. All compounds were cytotoxic at between 10 and 20 micro molar. Cytoskeletal and nuclear abnormalities were noted following drug exposure in all cell lines. These data suggest that possible mechanisms for the anti-migratory effect of these compounds include effects on F-actin localization and microtubule polarity. Inhibition of migration and cell architecture changes occurred at non-toxic doses. CONCLUSION: Inhibition of GSK3 significantly reduced migration of this highly invasive tumour. It is evident from these data that inhibiting the complex biological mechanisms driven by GSK3 may aid treatment of GBM through a number of different mechanisms.
Inappropriate Use of Fresh-Frozen Plasma
Authors: Harold A. Oberman
Journal: JAMA (1985)

Over the past decade hospitals throughout the United States have experienced a dramatic increase in utilization of freshfrozen plasma (FFP). Since this has paralleled a corresponding increase in transfusion of packed red blood cells in relation to whole blood, it may be inferred that much of the FFP is being transfused as a volume expander, rather than as a source of clotting factors or plasma proteins. Use of plasma in this manner not only increases the cost of transfusion, but also increases the risk of transfusion-transmitted disease. Therefore, the recent Consensus Development Conference on this subject, convened by the National Institutes of Health and reported in this issue ofThe Journal,<sup>1</sup>was both timely and appropriate. The conference concluded that there was "little scientific evidence to support the increasing use of FFP," especially as a volume expander, as there are safer products that will achieve the same effect. While
Microfinance Programs and Better Health
Authors: Paul M. Pronyk, James R. Hargreaves, Jonathan Morduch
Journal: JAMA (2007)

Although social gradients in morbidity and mortality from scrofula rickets and scarlet fever were noticed in England as early as 1845 current understanding of the relationship between  and ill health is still evolving. A detailed examination of the social determinants of health is the current focus of a World Health Organization Commission and a global agenda that addresses the overlapping vulnerabilities of  social exclusion and health recently has been articulated in the United Nations Millennium Development Goals (MDG) framework. Sub-Saharan Africa remains the area of the world at greatest risk of failing to meet any MDG targets. Some experts suggest that conditions of extreme deprivation characterizing much of the region create poverty traps that limit access to proven interventions and constrain potential gains in employment income food shelter and education carrying dire immediate and longer-term health consequences. The interdependence of  health and development might seem obvious but cross-sectoral experience on how and where to intervene remains limited. (excerpt)
VITAL STAINING OF THE CONNECTIVE TISSUES
Authors: Lester S. King
Journal: The Journal of Experimental Medicine (1938)

Trypan blue injected intravenously is bound almost at once by the intercellular connective tissue elements all over the body,-by collagen, reticulin, and elastic fibers. This union of dye and tissue elements is the factor responsible for the early macroscopic blue color and is antecedent to cellular colloidopexic action. Different examples of connective tissue differ among themselves in their ability to hold the dye. Diffuse staining of elastic fibers noted by previous observers is merely a special case of the general affinity of connective tissue for the dye. The evidence suggests that the histiocytes are cells specialized to segregate noxae that become diffusely bound to the intercellular connective tissue matrix.
Smoking, Propranolol, and Myocardial Infarction
Authors: M. E. McNabb
Journal: JAMA (1982)

<h3>To the Editor.—</h3> The β-Blocker Heart Attack Trial (BHAT) (1982;247:1707) was carried out in groups using propranolol hydrochloride and placebo, each of which contained 57% current smokers. It is important to examine the reported reduction in mortality in smokers and nonsmokers separately. Cigarette smoking is thought to have a role not only in the pathogenesis of coronary atherosclerosis, but also in aggravating angina, left ventricular dysfunction, and rhythm disturbances predisposing to sudden death.1 Epidemiologic studies have shown reduction in mortality from coronarydisease after smoking cessation.<sup>2</sup>While smoking exposes the body to numerous chemical agents, carbon monoxide and nicotine have been more often incriminated. The former affects oxygen transport. Nicotine from smoking cigarettes or from an intravenous bolus increased heart rate and BP.<sup>1,3</sup>Propranolol hydrochloride abolishes these adrenergically mediated hemodynamic effects attendant on smoking.<sup>4</sup>Until an analysis of the nonsmoking subjects of the BHAT demonstrates significant reduction in
Multiple-Puncture and Mantoux Tuberculin Tests in High School Students
Authors: George D. Hanzel, Kenneth D. Rogers
Journal: JAMA (1964)

Mantoux and multiple-puncture tuberculin tests were used to simultaneously test 1,914 high school students. All students received 0.1 cc of intermediate-strength purified protein derivative tuberculin (five tuberculin units) intradermally in one arm. In the other arm, tuberculin tine tests were given to 1,181 students and Heaf tests to 733. The reactor rate (positive to one or both tests) was approximately 4%. When compared to the Mantoux test, both multiple-puncture tests had high sensitivity and specificity. Ease and speed of administration constitute advantages of the multiple-puncture techniques over the Mantoux test for mass screening programs in high school students.
Antibiotic-Resistant Gonococci
Authors: Herman Goodman
Journal: JAMA (1962)

<h3>To the Editor:—</h3> With reference to the excellent answer (Antibiotic-Resistant Gonococci,<i>JAMA</i><b>179</b>:586 [Feb. 17] 1962) prepared by Dr. Schwimmer, I should like to state that there is reason why 3,000,000 units of procaine penicillin G (not just 1,800,000 units) could be used. I should like also to call attention to the much neglected genus of microorganisms, Mimeae, which have invalidated the diagnosis of gonorrhea by the smear method, and to<i>Neisseria fulva</i>and<i>Neisseria gigantea</i>which may also confuse the diagnosis.
Impact of audit on preventive measures.
Authors: D M Fleming, M S Lawrence
Journal: BMJ (1983)

The results of two reviews of practice records for information about various preventive measures are reported. The reviews were conducted two and a half years apart in the same 29 practices, on roughly 6500 records on each occasion. The first review was carried out during a postgraduate education course involving audit. Two main analyses were undertaken: one concerned with the entire record sample and the other with the individual practice results. Important and substantial improvements were shown in both analyses, which were spread throughout the practices and were not confined to practices at the lower end of the range simply "catching up." The change between the reviews in the mean recorded rates for cervical cytology was 56% to 64%; for rubella immunity 28% to 40%; for polio immunity in adults 15% to 21%; for completed primary immunisation 68% to 78%; for recorded blood pressure 53% to 61%; and for smoking information 22% to 30%. Improvement has been steady but the rate of improvement, especially for recording blood pressure and rubella immunity, has increased since the postgraduate education course.
Fundamentals of Aerospace Medicine
Authors: Jay C. Bisgard
Journal: JAMA (1986)

Perhaps the broad scope of aerospace medicine and the dynamic, rapidly evolving nature of the specialty make it unusually difficult to capture its wealth of information in a textbook. Certainly, this book is long overdue; the last similar text published in the United States appeared in 1971-a second edition of Harry G. Armstrong's 1961 classic. To fill the most recent gap, an excellent two-volume text,Aviation Medicine, by Air Marshal Sir Geoffrey Dhenin, was published in Great Britain in 1978.  Roy DeHart, a former Commander of the United States Air Force School of Aerospace Medicine, assembled nearly 50 contributors representing the spectrum of aerospace medicine disciplines. The authors of the various chapters are extremely well qualified in their fields, and their writing style is easy to read, considering the technical nature of the material. The book is aptly named—the editor has stuck to the fundamentals. More detail is covered in
Origin and Evolution of Influenza Virus Hemagglutinin Genes
Authors: Yoshiyuki Suzuki, Masatoshi Nei
Journal: Molecular Biology and Evolution (2002)

Influenza A, B, and C viruses are the etiological agents of influenza. Hemagglutinin (HA) is the major envelope glycoprotein of influenza A and B viruses, and hemagglutinin-esterase (HE) in influenza C viruses is a protein homologous to HA. Because influenza A virus pandemics in humans appear to occur when new subtypes of HA genes are introduced from aquatic birds that are known to be the natural reservoir of the viruses, an understanding of the origin and evolution of HA genes is of particular importance. We therefore conducted a phylogenetic analysis of HA and HE genes and showed that the influenza A and B virus HA genes diverged much earlier than the divergence between different subtypes of influenza A virus HA genes. The rate of amino acid substitution for A virus HAs from duck, a natural reservoir, was estimated to be 3.19 x 10(-4) per site per year, which was slower than that for human and swine A virus HAs but similar to that for influenza B and C virus HAs (HEs). Using this substitution rate from the duck, we estimated that the divergences between different subtypes of A virus HA genes occurred from several thousand to several hundred years ago. In particular, the earliest divergence time was estimated to be about 2,000 years ago. Also, the A virus HA gene diverged from the B virus HA gene about 4,000 years ago and from the C virus HE gene about 8,000 years ago. These time estimates are much earlier than the previous ones.
The Effect of Atrial Contraction on Left Ventricular Performance in Valvular Aortic Stenosis
Authors: FRANK W. KROETZ, JAMES J. LEONARD, JAMES A. SHAVER, DONALD F. LEON, JOHN F. LANCASTER, VIRGINIA L. BEAMER
Journal: Circulation (1967)

The instantaneous response of the left ventricle to loss or recovery of effective atrial contraction was studied in 12 patients with valvular aortic stenosis by producing A-V dissociation by electrical pacing of the ventricles so that some ventricular contractions were preceded by an effective atrial contraction while others were not. A conventional hydraulic formula relating size of the aortic valve orifice, pressure gradient, and flow was used to estimate beat to beat stroke volume. A properly timed atrial contraction augmented left ventricular performance in all patients, increasing stroke volume index from 14 to 55% (mean, 27%) and stroke work from 17 to 85% (mean, 45%). The contribution of atrial contraction to integrated cardiac performance was studied in six of the same patients by comparing cardiac performance with right atrial pacing and right ventricular pacing. With right atrial pacing, each ventricular contraction was preceded by an atrial contraction, while with right ventricular pacing many ventricular contractions were not preceded by atrial contraction. Right atrial pacing increased cardiac index in four of six patients: The mean increase for the total group was 13% and the mean increase in left ventricular minute work index was 17%. Although atrial contraction was capable of augmenting left ventricular performance in all patients studied, loss or recovery of effective atrial systole did not always alter integrated cardiac performance. Factors influencing atrial contribution remain poorly understood. Atrial contraction does not appear to have an unusual effect on the performance of the hypertrophied left ventricle.