tbuckley/cabot-search huggingface dataset:
Pesticides Studied in Man
Authors: Donald P. Morgan
Journal: JAMA (1982)

This book is the second major volume on pesticide toxicology written by Dr Hayes. His<i>Toxicology of Pesticides</i>(Williams and Wilkins Co, 1975) elaborated basic methods of toxicological investigation and demonstrated how these could be applied to the assessment of pesticide hazards.<i>Pesticides Studied in Man</i>is complementary to the first book, but is in no way duplicative. It is a comprehensive review and analysis of virtually all essential scientific information bearing on the toxic properties of several hundred pesticides. The book consists of 13 chapters, each dealing with a defined group of pesticides. Chemicals are grouped together on the basis of physical or chemical similarity (eg, "Organic Phosphorus Pesticides"), origin (eg, "Pesticides Derived From Plants and Other Organisms"), common target organisms (eg, "Herbicides") or a common toxic action (eg, "Synergists"). The final chapter discusses "Miscellaneous Pesticides." Of course, the various categories are not always mutually exclusive, but this approach
The Temporomandibular Syndrome, continued
Authors: August L. Stemmer
Journal: JAMA (1973)

<h3>To the Editor.—</h3> Although I am in agreement with Charles S. Greene's attempt (224:622, 1973) to bring the matter back to the interest of the physician, I would like to compare one small facet of the broad spectrum of temporomandibular joint causes to that of a patient with a backache instead of the vague headache symptom at issue. If one neglected the duty of apprising him of the possibility that the asymmetric function, induced by a fortuitously recognized long-term failure to replace the heel of one shoe, but instead simply directed him to a psychiatrist for such an "aberration," it would compare to the emphasis at issue that is placed upon the muscle spasm instead of the often only temporary functional disharmony of chronic muscle dyskinesia from failure of the usually well-aligned dental geometric factors. Thus, the problem of the temporal mandibular joint still has a major dental mechanistic aspect,
Surgical vs nonsurgical jaundice. Differentiation by a combination of rose bengal I-131 and standard liver-function tests
Authors: R. A. Nordyke
Journal: JAMA (1965)

The distinction between surgical and nonsurgical jaundice has been hindered by lack of a reliable test for biliary tract obstruction or patency. To meet this need, a method was devised which uses rose bengal I 131 and external body monitoring to determine whether dye flows through the biliary tract into the intestine. Simultaneously, liver function was estimated by a rose bengal I 131 blood disappearance rate. Among 181 jaundiced patients, three results were nearly diagnostic: the combination of "good" liver function and complete biliary tract obstruction (surgical), "poor" liver function alone (nonsurgical), and a patent biliary tract (nonsurgical). The most useful result was the correct classification of difficult nonsurgical patients by the demonstration of biliary tract patency. Among nonsurgical patients having biochemical tests which were either indeterminate or wrong, 80% were correctly classified by this finding.
Rates of Total Hip Arthroplasty
Authors: L.Joseph Melton, Richard N. Stauffer, Edmund Y. S. Chao, Duane M. Ilstrup
Journal: New England Journal of Medicine (1982)

Abstract Three hundred eighty-one total hip arthroplasties were performed on residents of Olmsted County, Minnesota, during the period from 1969 to 1980, for a rate (adjusted for sex and age) of 44.6 per 100,000 person-years. Rates rose with age, were higher for women than men, and were higher among urban than rural residents of the county. If we assume that the Olmsted County experience is medically optimal and apply it to the 1980 United States population, we calculate a national requirement of over 100,000 total hip arthroplasties per year, well above the current actual figure. If this calculated number of total hip arthroplasties were actually performed each year, over 1.4 million hospital days would be required, and direct medical costs would probably exceed $1 billion annually. (N Engl J Med. 1982; 307:1242–5.)
DOSAGE OF REDUCED IRON
Authors: William Dameshek
Journal: JAMA (1933)

<h3>To the Editor:</h3> —My attention has been called, particularly by Dr. Marie L. Cams of Madison, Wis., to an error in my recent article on "Primary Hypochromic Anemia," which appeared inThe Journal, February 25. I implied that reduced iron was ferrous oxide (FeO) and that its actual iron content was 78 per cent. This is incorrect. Reduced iron is metallic iron which has been produced by hydrogenating ferrous oxide, the resultant material being almost pure metallic iron, containing from 90 to 100 per cent of that metal. I have used this preparation in capsules containing 1 Gm. (15 grains), the daily dosage being from 3 to 6 Gm. The actual iron content at this dosage is extremely high, from 3,000 to 6,000 mg. of iron. It is probably necessary to use this large amount of actual iron because of the insolubility of the preparation. I have not found it
Molecular Pathways: The Metabolic Regulator Estrogen-Related Receptor α as a Therapeutic Target in Cancer
Authors: Ching-yi Chang, Donald P. McDonnell
Journal: Clinical Cancer Research (2012)

The estrogen-related receptor α (ERRα) is an orphan member of the nuclear receptor superfamily of transcription factors whose activity is regulated by the expression level and/or activity of its obligate coregulators, peroxisome proliferator-activated receptor γ coactivator-1 α and β (PGC-1α or PGC-1β). Under normal physiologic conditions, and in responding to different environmental stimuli, the ERRα/PGC-1 complex is involved in regulating metabolic homeostasis under conditions of high energy demand in brown adipocytes, proliferating T cells, and muscle. Interestingly, increased expression and activity of the ERRα/PGC-1 axis has also been shown to correlate with unfavorable clinical outcomes in both breast and ovarian tumors. The observation that ERRα activity is manifest in all breast tumor subtypes with particularly high activity being evident in ERα-negative, HER2-positive, and triple-negative breast cancers has raised significant interest in targeting this receptor for the treatment of those breast cancers for which therapeutic options are limited.
Frequent genomic alterations in epithelium measured by microsatellite instability following allogeneic hematopoietic cell transplantation in humans
Authors: Philipp Faber, Paul Fisch, Miguel Waterhouse, Annette Schmitt-Gräff, Hartmut Bertz, Jürgen Finke, Alexandros Spyridonidis
Journal: Blood (2005)
Treatment of Polycythemia Vera with Azauridine and Azaribine
Authors: RONALD C. DECONTI
Journal: Annals of Internal Medicine (1970)

The pyrimidine analog 6-azauridine or its oral derivative, azaribine, was used to control polycythemia vera in five patients. Amelioration of symptoms, decrease in splenomegaly, and progressive reduction of the hematocrit were uniformly achieved in 3 to 6 weeks without untoward effects. Reticulocytopenia, elevation in serum iron values, and prolongation of plasma iron disappearance time are in accord with the concept that suppression of erythropoiesis is responsible for these beneficial effects. The data suggest that this compound may be a useful agent in the management of polycythemia vera and that further studies are warranted.
Chronic idiopathic neutropenia: Granulopoietic assessment by both marrow culture and granulocyte kinetics
Authors: K. A. Rickard, R. D. Brown, E. Yuen, H. Kronenberg
Journal: American Journal of Hematology (1980)

Abstract Granulopoietic assessment was made in 14 patients with chronic idiopathic neutropenia (CIN) whose neutrophils were consistently less than 1.5 × 10 9 / liter and in whom there was absence of splenomegaly and recent drug ingestion. Granulopoiesis was studied using a combination of bone marrow culture in nutrient agar and granulocyte kinetics. Agar colony growth assessed bone marrow concentration of granulocyte progenitor cells (GPC) and the proportion of GPC in DNA synthesis by in vitro 3 HTdR suicide. Granulocyte kinetics with in vitro DF 32 P labelling of patient granulocytes measured granulocyte half‐life (T 1/2 ), turnover rate (GTR), and the circulating, marginated, and total blood granulocyte pools. The results indicated that either GPC concentration or the proportion of GPC in DNA synthesis was outside the normal range in all but one patient and decreased in ten out of 14 patients. CIN was also characterized by reduced total, circulating, and marginated blood granulocyte pools, reduced GTR, and normal granulocyte half‐life. The neutropenia appeared to be due to a variety of intra‐marrow causes, including either a reduction in the GPC compartment, a reduction in GPC proliferation, a maturation arrest, or a reduced amplication during granulopoiesis. Increased granulocyte utilization, intra‐vascular destruction or excessive margination could be excluded as possible causes of CIN in this series. Although GPC parameters tended to be reduced, suggesting a production defect, there were signs in nine patients that the bone marrow was attempting to compensate for the peripheral neutropenia. It is suggested that for a complete assessment of granulopoiesis in man, granulocyte kinetic studies need to be combined with quantitative studies of the bone marrow granulocyte progenitor compartment using the agar colony system.
S132 Sputum And Bronchial Biopsy Expression Of 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxodg) In Asthma Is Related To Neutrophilic Inflammation And Poor Asthma Control
Authors: D. Goold, V. Mistry, A. Singapuri, M. Cooke, R. Berair, C. Brightling
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> Oxidative stress has been implicated in the pathogenesis of asthma. Validated sputum biomarkers are required to assess this and its relationship to other clinical variables. We sought to compare sputum and bronchial 8-oxodG expression in asthma and health; assess the sputum repeatability; and explore its relationship with induced sputum inflammatory cells counts and exacerbations. <h3>Methods</h3> Asthmatics and healthy controls were recruited from a single centre and underwent clinical characterisation including sputum induction (asthma n = 58, health n = 27) and bronchial biopsy (asthma n = 16, health n = 10). Sputum and epithelial 8-oxodG expression was measured by ELISA and Immunohistochemistry respectively. Sputum asthmatics were assessed at a repeat stable visit at 6 months. <h3>Results</h3> Between health and asthma, there were no significant differences in the median (IQR) sputum 8-oxodG levels [12 (16) ngml<sup>-1</sup> vs. 11 (15) ngml<sup>-1</sup>, p = 0.36] or the mean (SEM) percentage area of epithelium reaching threshold intensity for 8-oxodG [2.0 (0.7)% vs. 4.4 (1.0) %, p = 0.12]. Asthma sputum 8-oxodG correlated with the sputum total cell count (<i>r</i><sub>s</sub>=0.53, p &lt; 0.01), sputum neutrophils (<i>r</i><sub>s</sub>=0.27, p = 0.04), sputum macrophages (<i>r</i><sub>s</sub>=-0.31, p = 0.02) and serum IgE (<i>r</i><sub>s</sub>=-0.27, p = 0.04). Epithelial 8-oxodG correlated to the number of exacerbations in the previous year (r<sub>s</sub>=0.70,p &lt; 0.01) and the ACQ 6 (r<sub>s</sub>=-0.52,p = 0.04). The upper 95th confidence interval of sputum 8-oxodG and epithelium 8-oxodG reaching threshold in healthy controls was used to split asthma patients into 8-oxodG <sup>high</sup> and <sup>low</sup> groups. The sputum 8-oxodG<sup>high</sup> group (n = 13) had significantly higher sputum total cells 8.08 [8.41] x10<sup>6</sup> g<sup>-1</sup> vs. 2.25 [2.91] x10<sup>6</sup> g<sup>-1</sup>, p &lt; 0.01, higher sputum neutrophils (82.25[32.75]% vs. 55.50 [29.75]%, p &lt; 0.01) and lower serum IgE (30 [76.50] KUL<sup>-1</sup> vs. 157 [212.90] KUL<sup>-1</sup>, p &lt; 0.01). The epithelial 8-oxodG <sup>high</sup> group (n = 8) had significantly more exacerbations 3.9 (0.3) vs. 0.5 (0.3) p &lt; 0.01 and a lower ACQ 6 score 1.4 (0.3) vs. 2.4 (0.3) p = 0.04. In the asthmatic group, the intra-class correlation coefficient of sputum 8-oxodG between the 2 visits was 0.51 (p &lt; 0.01). <h3>Conclusions</h3> 8-oxodG expression in sputum and bronchial biopsies was not different between asthma and health, although we did identify an 8-oxodG<sup>high</sup> group in asthma. Interestingly, expression in asthma was associated with neutrophilic inflammation and poor asthma control.
A Pragmatic Approach to the Diagnosis of Nodal Micrometastases in Early Stage Non-small Cell Lung Cancer
Authors: Esther Herpel, Thomas Muley, Thomas Schneider, Elisa Palm, Dörthe Kieslich de Hol, Arne Warth, Michael Meister, Konstantina Storz, Philipp A. Schnabel, Peter Schirmacher, Hendrik Dienemann, Hans Hoffmann
Journal: Journal of Thoracic Oncology (2010)
David Gardner-Medwin
Authors: A. Gulland
Journal: BMJ (2014)

Pioneered multidisciplinary team working for children with muscular dystrophy



David Gardner-Medwin, a paediatric neurologist, had broad interests outside medicine, but during his career he focused on the treatment and care of patients with Duchenne muscular dystrophy (DMD), a degenerative disease affecting boys. Despite advances there is still no cure for the disease, but when Gardner-Medwin—or DGM as he was known to his colleagues—first started working in this specialism in the 1960s, patients were not expected to live beyond their early teenage years.

His interest in the disease began when he was appointed a Medical Research Council research fellow under Professor John (now Lord) Walton in Newcastle, working on the early genetic associations of DMD. As a researcher he spent a long time with the families of children with the disease and learnt a great deal about the problems they faced. After a stint in the United States as a Harkness fellow, Gardner-Medwin was appointed consultant paediatric neurologist.

Because of his early contact with the children’s families, Gardner-Medwin realised the importance of a multidisciplinary team long before the phrase became fashionable. Professor Kate Bushby, a colleague of Gardner-Medwin’s and now …
The NHS bill puts profit before patients
Authors: Des Spence
Journal: BMJ (2012)

<b><i>Objective:</i></b> To determine the latency, magnitude, and duration of the long-duration response (LDR) to levodopa in PD in relationship to the administration of levodopa at different interdose intervals. <b><i>Methods:</i></b> In six patients with PD, two different 15-day treatment regimens were used in which the drug was administered with interdose intervals of 24 or 8 hours. <b><i>Results:</i></b> The LDR built up within a few days with either regimen, but a faster rate of administering levodopa shortened the latency to the appearance of a sustained LDR. Once a sustained response had been reached, the magnitude of the LDR showed a stable ceiling effect that was independent of the levodopa schedule. After discontinuation of treatment, the decay of the LDR was similar for both regimens. <b><i>Conclusions:</i></b> The system underlying the LDR to levodopa may be completely saturated when a sustained response has been fully developed. The intervals between doses of levodopa shorter than the interval effective to reach a sustained LDR should not be used in the clinical management of patients with PD because the antiparkinsonian benefit deriving from the LDR is already maximal and briefer intervals do not provide a greater benefit.
Endogenous Retrovirus Expression Is Required for Murine Melanoma Tumor Growth <i>In vivo</i>
Authors: Marianne Mangeney, Julien Pothlichet, Martial Renard, Bertrand Ducos, Thierry Heidmann
Journal: Cancer Research (2005)

Abstract Tumor development is a multistep process in which both genetic and epigenetic events cooperate for the emergence of a malignant clone. The possibility that endogenous retroviruses promote the expansion of a neoplastic clone by subverting immune surveillance has been proposed, but remained elusive. Here we show that knocking down—by RNA interference—an endogenous retrovirus spontaneously induced in the B16 murine melanoma results in the rejection of the tumor cells in immunocompetent mice, under conditions where control melanoma cells grow into lethal tumors. The knockdown does not modify the transformed phenotype of the cells, as measured both in vitro by a soft agar assay and in vivo by tumor cell proliferation in immunoincompetent (X-irradiated and severe combined immunodeficiency) mice. Tumor rejection can be reverted upon adoptive transfer of regulatory T cells from control melanoma-engrafted mice, as well as upon reexpression of the sole envelope gene of the endogenous retrovirus in the knocked down cells. These results show that endogenous retroviruses can be essential for a regulatory T-cell–mediated subversion of immune surveillance and could be relevant to human tumors where such elements—and especially their envelope gene—are induced.
In vivo rectal inflammatory mediator changes with radiotherapy to the pelvis.
Authors: A T Cole, K Slater, M Sokal, C J Hawkey
Journal: Gut (1993)

In vivo changes in the rectal values of eicosanoid inflammatory mediators induced by pelvic radiotherapy were measured to study the pathophysiology of the early radiation bowel reaction. Ten patients having pelvic radiotherapy, aged 57 to 78, had rectal dialysis. Values of the eicosanoids leukotriene B4 (LTB4), thromboxane B2 (TXB2), and prostaglandin E2 (PGE2) were measured before radiotherapy, at the end of radiotherapy, and at least four weeks after radiotherapy. Values of LTB4 rose with radiotherapy from 0.21 ng.ml-1 (median) to 1.14 ng.ml-1 (p = 0.012); PGE2 rose from 0.60 ng.ml-1 to 1.58 ng.ml-1 (p = 0.038), and TXB2 rose from 0.365 ng.ml-1 to 1.6 ng.ml-1 (p = 0.005). The rise in eicosanoid inflammatory mediators may have an important role in the pathophysiology of the early radiation bowel reaction.
Neonatal Jaundice and Maternal Oxytocin Infusion
Authors: D. P. Davies, R. Gomersall, R. Robertson, O. P. Gray, A. C. Turnbull
Journal: BMJ (1973)

A prospective study of 78 neonates provides evidence for an association between maternal oxytocin infusion and neonatal jaundice. On the second and fifth days infants of mothers whose labour had been induced by amniotomy followed immediately by intravenous oxytocin (group C) had mean total bilirubin levels significantly higher (P <0.05) than did infants whose mothers had had a spontaneous onset of labour and did not require oxytocin (group A). Bilirubin levels in infants of mothers whose onset of labour was spontaneous but required oxytocin to accelerate progress (group B) did not differ significantly from group A.Though these findings suggest a dose dependent effect of oxytocin, other possible explanations are suggested which take into account other drugs administered to the mother and also differences in the corticosteroid status of the groups of infants.
Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group
Authors: Yousif Matloub, Bruce C. Bostrom, Stephen P. Hunger, Linda C. Stork, Anne Angiolillo, Harland Sather, Mei La, Julie M. Gastier-Foster, Nyla A. Heerema, Scott Sailer, Patrick J. Buckley, Blythe Thomson, Catherine Cole, James B. Nachman, Gregory Reaman, Naomi Winick, William L. Carroll, Meenakshi Devidas, Paul S. Gaynon
Journal: Blood (2011)
STANDARDIZATION OF SCARLET FEVER PREPARATIONS
Authors: George F. Dick
Journal: JAMA (1924)

To the Editor:  —Many questions are being asked regarding scarlet fever preparations on the market. By cooperation with the United States Hygienic Laboratory, we believe that we have made it possible for commercial firms to place on the market potent and properly standardized scarlet fever toxin and concentrated scarlet fever antitoxin.  Whether or not any specified product meets the requirements that we suggested for these materials can probably be learned by inquiring of the Hygienic Laboratory of the U. S. Public Health Service. We cannot advise the use of any materials produced or standardized by other methods. Some such products are already on the market, but we have no first hand knowledge of their value, and no information as to the methods by which they were produced or standardized.  The need for careful standardization of the toxin is shown by the fact that any error in the skin test dose
TRAUMATIC RUPTURE OF THE FIXED PORTION OF THE MALE URETHRA
Authors: OTTO C. GAUB
Journal: JAMA (1910)

Traumatic rupture of the fixed portion of the male urethra is a most serious injury, both in its immediate aspect and remote consequences: immediately serious, because of leakage of urine following the several classical paths of extravasation, with subsequent decomposition, or on account of complicating lesions of osseous or soft tissues; remotely so, owing to formation of traumatic stricture, with its attendant urinary stagnation and infection of the entire urinary tract. The force causing a rupture of the urethra acts in one of two ways—in a direct manner, the patient falling astride an object, or indirectly, the pelvic bones being crushed together, the force usually acting in the coronal plane of the body. Produced in a direct manner, the urethral tear may be in a part anterior, within, or posterior to the layers of the triangular ligament, usually without complicating factors. Indirectly produced by crushing force, the tear in the
Sir Walter Langdon-Brown and hormonology at the RSM
Authors: M. Keynes
Journal: Journal of the Royal Society of Medicine (2005)

Examining the potential impact of the proposed two-year cut in otology training, Jaydip Ray and colleagues conclude that intensification of training would be necessary to eradicate the significant difference in specialist surgical experience between current year-four and year-six otology trainees (June 2005 JRSM 1 ).In our opinion their article misses the point regarding the changes.The proposed model of four years' general training followed by two years of specialist training will not require future year-four trainees to have comparable operative experience to today's year-six trainees, as implied.The Specialist Advisory Committee for Otolaryngology has set stage-specific criteria of required operative competencies for higher surgical trainees. 2Georgalas et al., 3 in a recent survey of otolaryngology trainees, concluded that all stage-specific criteria were currently being met, and that training standards were satisfactory across the UK.They concluded that current training is adequate and that a system of twotier trainees, with four years of general training and two years devoted to the subspecialties, would be an adequate option for the vast majority of specialist registrars, provided that current standards are maintained. 2 Training in specialist otological surgery will not be offered or assessed in the new four-year 'generalist' higher surgical rotations, since specialist experience will be gained in accredited otology fellowships for prospective otologists.