tbuckley/cabot-search huggingface dataset:
Assessment of hepatotoxic potential.
Authors: J E Gray
Journal: Environmental Health Perspectives (1976)

Philosophic concepts and pragmatic approaches toward improved understanding of the effect of drugs in the hepatocyte are reviewed. No set pattern of studies is advocated but rather observations are encouraged within the framework of studies that provide for varied exposure of the hepatocyte. Clinical usage should be imitated to provide earliest possible indications of toxicity in man. The need for definitive characterization through utilization of appropriate methodology derived from cross-fertilization of related disciplines is stressed. Both minimal and maximal dose effects should be established. Selected use of electron microscopy has become essential for characterizing responses of the liver to injury. The advantages of the toluidine blue-stained Epon "thick" sections are emphasized. Such observations are used to implement the utility of serial biopsies from the beagle dog prior to and during long-term study of potential hepatic injury. Examples of the critical effects of drug concentration within the hepatocyte are presented.
TREATMENT OF THE GASTROINTESTINAL SYMPTOMS IN TYPHOID FEVER.
Authors: J. M. ANDERS
Journal: JAMA (1901)

While we have no direct specific remedy for typhoid fever, and no knowledge of any drug that destroys the bacillus of this disease, the proper management of the gastrointestinal system, and especially during the early period, will prove of decided advantage. Among the principal objects met in this way is the preservation of the strength and vitality of the patient, thus probably inhibiting the virulence of the bacilli and their toxins, as well as that of some of the intestinal organisms which are otherwise harmless. Moreover, we can diminish somewhat the amount of intestinal toxins, and hence to an equal extent their absorption into the general system. The frequency of certain symptoms and complications—meteorism, vomiting, diarrhea—which are so very prone to manifest themselves if the prima via be neglected, may also be lessened. Before discussing the usefulness of drugs in this condition, which I grant are subsidiary in importance to
MORTALITY FROM CANCER
Authors: Frederick L. Hoffman
Journal: JAMA (1923)

<h3>To the Editor:</h3> —I have recently had occasion to consider the mortality statistics from cancer of a number of representative governments. ("Cancer and Civilization,"<i>Prudential Press</i>, Newark, N, J., 1923). In this investigation I was not able to give extended consideration to Asiatic governments for which trustworthy statistics are available. However, I here present certain statistics for Japan which may be of interest to your readers, together with a brief table of the cancer mortality of five cities of Finland. I have not been able to secure the cancer mortality statistics of Japan for 1919. (Furnished by the Statistical Division, Army Medical Library, Washington, D. C.) Table 1 shows the mortality from all forms of cancer in Japan during the period 1911-1921, excluding 1919. According to this table, the cancer death rate of Japan during the present decade has increased from 66.9 to 76.1 per hundred thousand of population. The
Nephrolithiasis and Osteoporosis Associated with Hypophosphatemia Caused by Mutations in the Type 2a Sodium–Phosphate Cotransporter
Authors: Dominique Prié, Virginie Huart, Naziha Bakouh, Gabrielle Planelles, Olivier Dellis, Bénédicte Gérard, Philippe Hulin, François Benqué-Blanchet, Caroline Silve, Bernard Grandchamp, Gérard Friedlander
Journal: New England Journal of Medicine (2002)

Epidemiologic studies suggest that genetic factors confer a predisposition to the formation of renal calcium stones or bone demineralization. Low serum phosphate concentrations due to a decrease in renal phosphate reabsorption have been reported in some patients with these conditions, suggesting that genetic factors leading to a decrease in renal phosphate reabsorption may contribute to them. We hypothesized that mutations in the gene coding for the main renal sodium-phosphate cotransporter (NPT2a) may be present in patients with these disorders.We studied 20 patients with urolithiasis or bone demineralization and persistent idiopathic hypophosphatemia associated with a decrease in maximal renal phosphate reabsorption. The coding region of the gene for NPT2a was sequenced in all patients. The functional consequences of the mutations identified were analyzed by expressing the mutated RNA in Xenopus laevis oocytes.Two patients, one with recurrent urolithiasis and one with bone demineralization, were heterozygous for two distinct mutations. One mutation resulted in the substitution of phenylalanine for alanine at position 48, and the other in a substitution of methionine for valine at position 147. Phosphate-induced current and sodium-dependent phosphate uptake were impaired in oocytes expressing the mutant NPT2a. Coinjection of oocytes with wild-type and mutant RNA indicated that the mutant protein had altered function.Heterozygous mutations in the NPT2a gene may be responsible for hypophosphatemia and urinary phosphate loss in persons with urolithiasis or bone demineralization.
Improvement of regional myocardial metabolism after coronary thrombolysis induced with tissue-type plasminogen activator or streptokinase.
Authors: B E Sobel, E M Geltman, A J Tiefenbrunn, A S Jaffe, J J Spadaro, M M Ter-Pogossian, D Collen, P A Ludbrook
Journal: Circulation (1984)

To assess the effects on the heart itself of coronary thrombolysis induced with either tissue-type plasminogen activator (t-PA) or streptokinase (SK), we performed positron emission tomography with 11C-palmitate in 19 patients with initial transmural myocardial infarction immediately after admission and again within 48 to 72 hr after intracoronary administration of t-PA (n = 2) or SK (n = 17). Clots were persistent in eight patients treated with SK despite an average dose of 336,000 IU, sufficient to markedly deplete fibrinogen. In the absence of lysis, favorable tomographic changes did not occur. In contrast, in each of the 11 patients in whom lysis was induced (two with t-PA and nine with SK) myocardial accumulation of 11C-palmitate improved by an average of 29% in late compared with early studies (p less than .001). Results were comparable in patients with anterior and those with inferior infarction. Thus clot lysis induced with either t-PA or SK led to improved regional myocardial metabolism.
112 URINE PROTEOMIC ANALYSIS DIFFERENTIATES CHOLANGIOCARCINOMA FROM PRIMARY SCLEROSING CHOLANGITIS AND OTHER BENIGN BILIARY DISEASES
Authors: J. Metzger, A. Negm, R. Plentz, T. Weismüller, J. Wedemeyer, T. Karlsen, H. Mischak, M. Manns, T. Lankisch
Journal: Journal of Hepatology (2012)
Itch: Role of Prostaglandins
Authors: M. W. Greaves, W. McDonald-Gibson
Journal: BMJ (1973)

Prostaglandin E<sub>1</sub> lowers the threshold of human skin to histamine-evoked itching. Though histamine and other mediators may produce itching by a direct action, itching in inflamed skin can also be explained by a pharmacological synergism in which low concentrations of prostaglandins, which do not themselves cause itching, potentiate itching due to histamine and possibly other agents. Alteration of threshold responses of components of inflammation to other mediators may be an important general role of prostaglandins.
Patient preferences for treatment: report from a randomised comparison of treatment strategies in early rheumatoid arthritis (BeSt trial)
Authors: Y. P M Goekoop-Ruiterman, J. K de Vries-Bouwstra, C. F Allaart, P. J S M Kerstens, B. A M Grillet, M. H de Jager, K H. Han, I. Speyer, P. A H M van der Lubbe, P. E H Seys, F. C Breedveld, B. A C Dijkmans
Journal: Annals of the Rheumatic Diseases (2007)

<b>Objective:</b> To determine treatment preferences among patients with recent onset rheumatoid arthritis participating in a randomised controlled trial comparing four therapeutic strategies. <b>Methods:</b> A questionnaire was sent to all 508 participants of the BeSt trial, treated for an average of 2.2 years with either sequential monotherapy (group 1), step-up combination therapy (group 2), initial combination therapy with tapered high-dose prednisone (group 3), or initial combination therapy with infliximab (group 4). Treatment adjustments were made every 3 months to achieve low disease activity (DAS ⩽2.4). The questionnaire explored patients' preferences or dislikes for the initial therapy. <b>Results:</b> In total, 440 patients (87%) completed the questionnaire. Despite virtually equal study outcomes at 2 years, more patients in group 4 reported much or very much improvement of general health: 50%, 56%, 46% and 74% in groups 1–4, respectively (overall, P&lt;0.001). Almost half of the patients expressed no preference or aversion for a particular treatment group, 33% had hoped for assignment to group 4 and 38% had hoped against assignment to group 3. This negative perception was much less prominent in patients actually in group 3. Nevertheless, 50% of patients in group 3 disliked having to take prednisone, while only 8% in group 4 disliked going to the hospital for intravenous treatment. <b>Conclusions:</b> Within the limitations of our retrospective study, patients clearly preferred initial combination therapy with infliximab and disliked taking prednisone. After actual exposure, this preference remained, but the perception of prednisone improved. Patient perceptions need to be addressed when administering treatment.
Editorial: The patient needs
Authors: H. H. Hussey
Journal: JAMA (1974)

Late summer 1973 found the famous columnist Sydney J. Harris enduring a protracted stay in a highly regarded teaching hospital. There he underwent a major surgical operation, and, as might have been expected, he later wrote about his experiences in a series of three articles published in<i>Chicago Daily News</i>on Nov 5, 6, and 7, 1973. He stated that he knew his odds of eluding death and of recovery were high, thanks to medical advances, that his own care was rather better than average, "yet even this—with the best will in the world on the part of the top people— was only haphazardly translated down to the lower levels, where the quality of care depended on who happened to be on duty at what hour." Most poignant of all, Mr. Harris observed that during his convalescence, when his psychological needs for attention were strongest, his treatment was most impersonal
Essential role of BRG, the ATPase subunit of BAF chromatin remodeling complexes, in leukemia maintenance
Authors: Manuel Buscarlet, Veneta Krasteva, Lena Ho, Camille Simon, Josée Hébert, Brian Wilhelm, Gerald R. Crabtree, Guy Sauvageau, Pierre Thibault, Julie A. Lessard
Journal: Blood (2014)
Phased Chest and Abdominal Compression-Decompression
Authors: Wanchun Tang, Max Harry Weil, Robert B. Schock, Yoji Sato, John Lucas, Shijie Sun, Joe Bisera
Journal: Circulation (1997)

Background We describe a new manual method of phased chest and abdominal compression-decompression with a Lifestick resuscitator for cardiopulmonary resuscitation (CPR). Methods and Results Ventricular fibrillation (VF) was induced in 20 domestic pigs. After either 5 or 7 minutes of untreated VF, either phased chest and abdominal compression-decompression (Lifestick resuscitator) or precordial compression was initiated. Defibrillation was attempted at 2 minutes after the start of CPR. For the animals in which VF was untreated for 7 minutes, epinephrine was administered in doses of 20 μg/kg at 2 minutes after start of CPR. The coronary perfusion pressure generated by the Lifestick resuscitator was more than twofold greater ( P &lt;.01) than that generated by conventional precordial compression. Of 5 control animals, none were resuscitated after 5 minutes of VF. However, each of 5 animals treated with the Lifestick resuscitator was resuscitated ( P &lt;.01) and survived after 48 hours ( P &lt;.01). When untreated VF was prolonged to 7 minutes and epinephrine was administered, only 2 of the 5 control animals were resuscitated, and none of them survived for more than 4 hours. However, each of the Lifestick-treated animals was resuscitated and survived for more than 48 hours ( P &lt;.01). Conclusions Phased chest and abdominal compression-decompression substantially increased hemodynamic efficacy of CPR and outcome in terms of successful resuscitation, 48-hour survival, and cerebral recovery.
Cardiac Aneurysm with Ventricular Tachycardia and Subsequent Excision of Aneurysm
Authors: O. A. COUCH
Journal: Circulation (1959)

A case of ventricular tachycardia in a patient with an anterolateral ventricular aneurysm is reported. The aneurysm was excised and the ventricular tachycardia did not recur, despite discontinuation of quinidine.
STUDIES ON THE COMPETENCE OF SINGLE CELLS TO PRODUCE ANTIBODIES OF TWO SPECIFICITIES
Authors: Harriet Gershon, Sara Bauminger, Michael Sela, Michael Feldman
Journal: The Journal of Experimental Medicine (1968)

Two series of experiments were performed, utilizing a modification of the hemolysin plaque technique which registers 19S antibody, in an attempt to determine the frequency of cells capable of simultaneously producing antibody to two non-cross-reacting antigens. Mice were immunized i.v. with rabbit and camel RBC and their spleens assayed for cells producing antibody against both antigens. 16,904 cells producing antibody of one or the other specificity, from 26 mice, were counted. Not one cell was detected which produced antibody of two specificities. Rabbits were immunized intradermally with HSA to which polyalanyl and p-azobenzenearsonate groups were chemically attached. The individual haptens, polyalanyl, and p-azobenzenearsonate groups were coupled to separate aliquots of SRBC, and the lymph nodes of immunized rabbits were assayed for cells releasing antibody against both haptens. In a study of 11 rabbits, after counting 27,845 cells producing antibody, we detected no "double" plaques.
Breast Cancer Risk in Metabolically Healthy but Overweight Postmenopausal Women
Authors: Marc J. Gunter, Xianhong Xie, Xiaonan Xue, Geoffrey C. Kabat, Thomas E. Rohan, Sylvia Wassertheil-Smoller, Gloria Y.F. Ho, Judith Wylie-Rosett, Theresa Greco, Herbert Yu, Jeannette Beasley, Howard D. Strickler
Journal: Cancer Research (2015)

Adiposity is an established risk factor for postmenopausal breast cancer. Recent data suggest that high insulin levels in overweight women may play a major role in this relationship, due to insulin's mitogenic/antiapoptotic activity. However, whether overweight women who are metabolically healthy (i.e., normal insulin sensitivity) have elevated risk of breast cancer is unknown. We investigated whether overweight women with normal insulin sensitivity [i.e., homeostasis model assessment of insulin resistance (HOMA-IR) index, or fasting insulin level, within the lowest quartile (q1)] have increased breast cancer risk. Subjects were incident breast cancer cases (N = 497) and a subcohort (N = 2,830) of Women's Health Initiative (WHI) participants with available fasting insulin and glucose levels. In multivariate Cox models, metabolically healthy overweight women, defined using HOMA-IR, were not at elevated risk of breast cancer compared with metabolically healthy normal weight women [HRHOMA-IR, 0.96; 95% confidence interval (CI), 0.64-1.42]. In contrast, the risk among women with high (q3-4) HOMA-IRs was elevated whether they were overweight (HRHOMA-IR, 1.76; 95% CI, 1.19-2.60) or normal weight (HRHOMA-IR, 1.80; 95% CI, 0.88-3.70). Similarly, using fasting insulin to define metabolic health, metabolically unhealthy women (insulin q3-4) were at higher risk of breast cancer regardless of whether they were normal weight (HRinsulin, 2.06; 95% CI, 1.01-4.22) or overweight (HRinsulin, 2.01; 95% CI, 1.35-2.99), whereas metabolically healthy overweight women did not have significantly increased risk of breast cancer (HRinsulin, 0.96; 95% CI, 0.64-1.42) relative to metabolically healthy normal weight women. Metabolic health (e.g., HOMA-IR or fasting insulin) may be more biologically relevant and more useful for breast cancer risk stratification than adiposity per se.
Acid secretory response to graded doses of histamine after 'medical vagotomy'.
Authors: S Raju, F M Narielvala
Journal: Gut (1966)

<i>Chlamydia trachomatis</i> infection is the most common sexually transmitted bacterial infection in the United States and a significant health burden worldwide. Protection from <i>Chlamydia</i> infection in the genital mucosa is dependent on IFN-γ derived from CD4<sup>+</sup> Th1 cells. These CD4<sup>+</sup> T cells must home successfully to the genital tract to exert their effector function and decrease <i>C. trachomatis</i> burden. Although adhesion receptors expressed by CD4<sup>+</sup> T cells in the genital tract have been characterized, the integrin receptor required for <i>Chlamydia</i>-specific CD4<sup>+</sup> T cell–mediated protection has not been explored. In this study, we demonstrate that <i>C. trachomatis</i> infection of the upper genital tract results in recruitment of <i>Chlamydia</i>-specific CD4<sup>+</sup> T cells robustly expressing the integrin α<sub>4</sub>β<sub>1</sub>. Interfering with α<sub>4</sub>β<sub>1</sub>, but not α<sub>4</sub>β<sub>7</sub>, function resulted in defective CD4<sup>+</sup> T cell trafficking to the uterus and high bacterial load. We conclude that integrin α<sub>4</sub>β<sub>1</sub> is necessary for CD4<sup>+</sup> T cell–mediated protection against <i>C. trachomatis</i> infection in the genital mucosa. By identifying homing molecules required for successful CD4<sup>+</sup> T cell trafficking to <i>C. trachomatis</i>–infected tissues, we will be better equipped to design vaccines that elicit sterilizing, long-lasting immunity without inducing immune pathologies in the upper genital tract.
A Difficult Balance: Editorial Peer Review in Medicine
Authors: Martha J. Carney
Journal: JAMA (1986)

STEPHEN Lock, the eminent, long-time editor of the<i>British Medical Journal</i>, has written a fascinating 179-page hardcover book,<i>A Difficult Balance: Editorial Peer Review in Medicine</i>,<sup>1</sup>that is useful for all editors of biomedical journals as well as authors and researchers who contribute to those journals. Dr Lock presents a comprehensive analysis of editorial peer review, looking at the merits and defects in the system from the viewpoint of many authorities. His analysis is challenging, making authors, editors, and reviewers think afresh about all the issues surrounding peer review in medical editing. Given the large amount of research and well-informed discussion that is surely needed on this topic, Lock's analysis raises many questions. In tackling the question of "What's wrong with peer review?" he discusses specific components of the process and the outcome by studying the assessors (interchangeably referred to as "reviewers," "referees," and "consultants"). He also discusses authors
THE COMPARATIVE EFFICIENCY OF SOME COMMON GERMICIDES
Authors: WILBUR E. POST
Journal: JAMA (1910)

In the case of an obstinate gonorrheal arthritis in a hospital, the advisability of injecting argyrol into the joint arose and the question was asked, What is the germicidal power of this preparation? The literature seemed indefinite and various in its answers and tests were accordingly made. The results were so unexpected and so much at variance with the prevalent opinion that the tests were repeated and extended to protargol, and silver nitrate, and from these to a considerable number of germicides in ordinary use for clinical purposes in a large well-regulated hospital. As a consequence of the evidence produced, many solutions previously in use in that hospital have been discarded and in their place more effective ones substituted. Because of the daily interest of clinicians, as well as the importance of the subject to patients, a summary of these investigations is here presented. The development of methods for testing
THE INFLUENCE OF THE LIVER ON PHENOLSULPHONEPHTHALEIN EXCRETION
Authors: RALPH H. MAJOR
Journal: JAMA (1923)

The frequent occurrence of low phenolsulphonephthalein excretion in certain persons without suspicion or evidence of renal disease must have attracted the attention of many observers. In our clinic, while studying the excretion of creatinin in health and in disease, a low excretion of phenolsulphonephthalein has been rather frequently observed in patients who excreted creatinin in a normal fashion, whose blood on chemical analysis and whose blood pressure were normal, and whose urine contained no albumin, sugar, casts or other evidence of renal impairment. Further tests in these normal controls showed, at times, a normal excretion of phenolsulphonephthalein, at other times, a marked diminution.<sup>1</sup> The low values in phenolsulphonephthalein excretion were seen more often following intravenous injection, but were also noted at times after intramuscular injections. Six normal persons, showing a two-hour urinary excretion of from 35 to 40 per cent., showed three and four days later an excretion of
MENTAL CHANGES INCLUDING APHASIA IN A PATIENT WITH SICKLE CELL ANEMIA
Authors: Beulah Bosselman, S. H. Kraines
Journal: American Journal of Psychiatry (1937)

The case is reported of a colored boy, aged 13, with sickle cell anemia who suddenly developed mental changes including aphasia. The occurrence of multiple small cerebral hemorrhages is suggested as the most likely cause of the symptoms.
Simultaneous Mutation Detection in 90 Retinal Disease Genes in Multiple Patients Using a Custom-designed 300-kb Retinal Resequencing Chip
Authors: Judith C. Booij, Arne Bakker, Jamilia Kulumbetova, Youssef Moutaoukil, Bert Smeets, Joke Verheij, Hester Y. Kroes, Caroline C.W. Klaver, Mary van Schooneveld, Arthur A.B. Bergen, Ralph J. Florijn
Journal: Ophthalmology (2010)
Pictures from the past
Authors: Fred Charatan
Journal: BMJ (2006)

Recently I came across a small illustrated book, Jewish Life in Canada , published in 1976 by the artist William Kurelek and coauthor Abraham Arnold. An unusual name, Kurelek, stirred an old memory.

In 1953 I was working as a senior registrar at the Maudsley Hospital in London. One day, a young man aged 26 came to the hospital's front door depressed, dishevelled, and disorganised, and in obvious need of psychiatric care. The patient was assigned to me, and his history soon emerged.

He was of Ukrainian heritage, raised on a Canadian farm, …
Treatment of Empyema
Authors: J. G. Scadding
Journal: BMJ (1935)

QUESTION: A 34-year-old patient of mine is taking a 9statin9 for hyperlipidemia. She is planning pregnancy and is worried about the safety of the drug. How should I advise her? ANSWER: Limited evidence from animal and human studies indicates that statins should not be taken during pregnancy. If a patient is inadvertently exposed during pregnancy, however, termination does not appear to be medically indicated.
PATHOLOGY OF TUBERCULOUS GLANDS OF THE NECK; THEIR EARLY AND COMPLETE REMOVAL.
Authors: E. LAPLACE
Journal: JAMA (1898)

That form of adenitis so frequent during adolescence and middle age, wherein tubercle bacilli invade the lymphatic glands of the neck, is one of the most important pathologic conditions which come to the observation of the surgeon. The infection of tuberculosis, and its local development in the lymphatic glands of the neck, naturally presents the strongest grounds for fearing the dissemination of the infection to other and more important structures in the body. These enlarged glands may retain their hyperperplasia a varying length of time, but during this time the toxins generated on the spot are absorbed to the detriment and weakening of various structures in the body. The subsequent acute infection, due to streptococci, invades the tuberculous gland, transforming it into an acute abscess, which sometimes brings a spontaneous termination of the tuberculous development. This lymph-adenitis may be limited to some of the superficial or may exist in the