tbuckley/cabot-search huggingface dataset:
Genethics: The Clash Between the New Genetics and Human Values
Authors: Richard C. Hermann
Journal: JAMA (1990)

Recent headlines heralding advances in genetics research are challenging the notion that science progresses slowly. Researchers at the Universities of Michigan and Toronto locate the genetic defect in cystic fibrosis. Cornell scientists take a historic step by releasing a genetically altered virus on a field of crops. James Watson, as if stepping out of history, presents the National Institutes of Health's Human Genome Initiative to Congress. Characterized by one biomedical pilgrim as the "holy grail" of human genetics, the Genome Initiative will attempt to sequence and map the estimated 3 billion nucleotide base pairs and 100 000 genes that encode the species<i>Homo sapiens</i>. What are we, as physicians or lay people, to make of this continual parade of breakthroughs? What are the possibilities for treating cystic fibrosis? What are the implications of a screening test for carriers? Is the release of a genetically altered virus a step toward the
Smallpox Vaccination in Fairfield, 1782
Authors: David L. Ellrich
Journal: JAMA (1964)

<h3>To the Editor:—</h3> In your communication on Benjamin Waterhouse—The American Jenner (<i>JAMA</i><b>188</b>:929 [June 8] 1964) you stated that he began his work with smallpox vaccination in June, 1800. I have an interesting document in my possession indicating that this procedure was practiced in my locality much before that time. It is in longhand and is quoted as follows: Fairfield, April 21-1782 These certify that we permit the wife of Joshua Jennings of Greens Farms in Fairfield to be innoculated for the Smallpox and to receive said infection by innoculation—she having been involuntarily exposed to have taken sd. infection. And. Rowland Gould S. Silliman Abram. Andrews Sam'l Squier Gershom Hubbell Increase Bradley Jus[tices of] Peace Thaddeus Burr David Allen } Selectmen Nehemiah Banks J I presume this gave the local physician legal permission to go ahead with the vaccination procedure.
Obesity in Pregnancy: The Effect of Dietary Advice
Authors: C Borberg, M D G Gillmer, E J Brunner, Philippa J Gunn, N W Oakley, R W Beard
Journal: Diabetes Care (1980)

Plasma glucose and insulin concentrations, body weight, and skinfold thickness were measured at 16 and 36 wk of pregnancy and 5–7 days after delivery in 37 women with normal glucose tolerance. Nine thin women [less than 80% ideal body weight (IBW)], 10 normal women (90-110% IBW), and 10 obese women (more than 120% IBW) were allowed to eat according to appetite. Another eight obese women were advised to restrict their carbohydrate intake to between 150 and 180 g while maintaining the calorie content of their diet between 1800 and 2000 cal. The thin, normal, and obese women displayed a net weight increase between 16 wk and 5–7 days after delivery of 6.3, 2.8, and 4.9 kg, respectively. The dieted obese women, however, showed a mean weight loss of 2.3 kg. There was a strong association between the overall pregnancy weight gain and the change in skinfold measurements between 16 wk and delivery in the women studied. A significant decrease in glucose tolerance was observed in all four groups, although this was least in the dieted women and greatest in the thin. The mean basal and glucose-stimulated insulin concentrations of the two obese groups were found to be significantly higher at 16 wk than those of the normal women. In the thin, normal, and obese subjects the mean basal and glucose-stimulated insulin concentrations at 36 wk were double those observed at 16 wk of pregnancy. A much smaller increase in insulin concentrations occurred between 16 and 36 wk in the dieted obese group. It is concluded that obesity preceding pregnancy produces a stress on carbohydrate metabolism, which can be ameliorated if an isocaloric diet with mild carbohydrate restriction is advised. No adverse effect on neonatal outcome was observed.
Malaria Relapse
Authors: D. Kirk Spitler
Journal: New England Journal of Medicine (1948)

THE problems of malaria control and treatment after the return of personnel from endemic areas have frequently been reported in the recent literature.1 Not the least of these problems is the matter of relapse. Whereas this usually occurs within the first two or three months, there are reports of initial relapse one and a half to two and a half years after the original attack.2 Relapses at longer periods have been observed, but these are in persons with recurring relapse, such as Ross's father, who suffered from repeated attacks for nine years after leaving an endemic area.3 The following case, . . .
Indirect Support for the Use of Supplemental Insulin in Hospitalized Insulin-Requiring Diabetic Patients
Authors: Mayer B. Davidson, Stanton Dulan, Petra Duran, Mohsen Bazargan
Journal: Diabetes Care (2004)

Hyperglycemia has detrimental effects on many physiological processes, e.g., causing phagocytic dysfunction, immune suppression, enhanced thrombosis, and increased inflammation (1). This translates into worse outcomes in those hospitalized patients with stroke, myocardial infarction, or sepsis (1).

A common method for treating hyperglycemia in hospitalized patients utilizes a sliding scale approach with short-acting insulin. There is general agreement in the literature that the sliding scale method is not very effective (2–14). A major reason is the underlying rationale for the sliding scale method, i.e., one waits until the glucose concentration reaches a certain level (often 200 mg/dl) before one treats it. Thus, instead of attempting to prevent hyperglycemia, this approach waits until it occurs before dealing with it.

There have never been (and probably never will be) published randomized trials comparing different modes of treating hyperglycemia in hospitalized patients. Based on the poor outcome of the sliding scale method (2–14 …
Treatment of solid organ transplant recipients with autologous Epstein Barr virus–specific cytotoxic T lymphocytes (CTLs)
Authors: Barbara Savoldo, John A. Goss, Markus M. Hammer, Lan Zhang, Teresita Lopez, Adrian P. Gee, Yu-Feng Lin, Ruben E. Quiros-Tejeira, Petra Reinke, Stephan Schubert, Stephen Gottschalk, Milton J. Finegold, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop
Journal: Blood (2006)
Met as a therapeutic target in HCC: Facts and hopes
Authors: Silvia Giordano, Amedeo Columbano
Journal: Journal of Hepatology (2013)

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and its burden is expected to increase further in the next years. In spite of the advances of classical therapies, such as surgery, transplantation, use of radiofrequency and transarterial embolization, the prognosis of this neoplasm has not considerably improved over the past few years. The advent of targeted therapies and the approval of the systemic treatment of advanced HCC with the kinase inhibitor sorafenib have provided some hope for the future. Even if the molecular mechanisms responsible for the onset and progression of HCC are still largely unknown, new therapeutic targets have recently come to the spotlight. One of these targets is the tyrosine kinase receptor for the Hepatocyte Growth Factor, encoded by the MET gene, known to promote tumor growth and metastasis in many human organs. In this review we will summarize the contrasting results obtained in vitro (in HCC cell lines) and in animal experimental models and we will also try to analyze the reasons for the opposite findings, suggesting that the HGF/MET axis can have either a promoting or a suppressive role in the development of HCC. We will also reconsider the evidence of activation of this pathway in human HCCs and discuss the results of the clinical trials performed with MET inhibitors. The final purpose is to better clarify which can be the role of MET as a therapeutic target in HCC.
Hypoglycemia was associated with increased mortality in ICU patients regardless of glucose control strategy
Authors: Todd W. Rice
Journal: Annals of Internal Medicine (2013)

ACP Journal Club15 January 2013Hypoglycemia was associated with increased mortality in ICU patients regardless of glucose control strategyTodd W. Rice, MD, MScTodd W. Rice, MD, MScVanderbilt University School of Medicine, Nashville, Tennessee, USA (T.W.R.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-158-2-201301150-02003 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationNICE-SUGAR Study Investigators, Finfer S, Liu B, et al. Hypoglycemia and risk of death in critically ill patients. N Engl J Med. 2012;367:1108-18. https://pubmed.ncbi.nlm.nih.gov/22992074Clinical Impact RatingsHospitalists: Endocrinology: Critical Care: References1 Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345:1359-67. [PMID: 11794168] Google Scholar2 Griesdale DE, de Souza RJ, van Dam RM, et al. Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data. CMAJ. 2009;180:821-7. [PMID: 19318387] Google Scholar3 Brunkhorst FM, Engel C, Bloos F, et al; German Competence Network Sepsis (SepNet). Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008;358:125-39. [PMID: 18184958] Google Scholar Author, Article, and Disclosure InformationAffiliations: Vanderbilt University School of Medicine, Nashville, Tennessee, USA (T.W.R.)This article was published at Annals.org on 1 January 2013. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByDiabetisches Koma und perioperative DiabetestherapieDiabetisches Koma und perioperative Diabetestherapie 15 January 2013Volume 158, Issue 2Page: JC3KeywordsAlgorithmsBloodCorticosteroid therapyGlucoseHyperglycemiaHypoglycemiaInsulinIntensive care unitsSepsis ePublished: 15 January 2013 Issue Published: 15 January 2013 CopyrightCopyright © 2013 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
The 'Impermeable Piline' a Remedy for Burns
Authors: A. Markwick
Journal: BMJ (1848)

Although Tarious plans of treating burns and scalds bate been recommended by different writers, still the chief indication seems ever to have been to exclude the air from the injured part, and thereby alleviate as speedily as possible the sufferings of the patient.The remedies, therefore, that have been employed in these cases, have all been more or less directed towards accomplishing this most desirable object.Indeed it is evident that this must always be of paramount importance, inasmuch as the prognosis is found to be depend- ent more on the extent than on the severity of the injury, for, as is well known, burns and scalds, even of the first degree, when extensive, often prove fatal,
Radiology of the Acute Abdomen in the Newborn: A Self-Teaching Manual
Authors: William L. Schey
Journal: JAMA (1979)

This apparently and deceptively short elementary teaching manual is in reality a relatively complete discussion of the acute abdomen in the neonate. The approach to the included material, which emphasizes the mechanical (surgical) problems, is comprehensive, and the case selection and roentgenogram reproductions are both excellent. The author states in the preface that he attempted to achieve three main goals: (1) to demonstrate the diagnostic approach, (2) to provide a detailed comprehensive text, and (3) to allow the reader to review the specific information for which he is looking. I believe with some reservations that he has achieved these goals. The approach uses a film presentation and challenge to the reader followed by an explanation of the findings, analysis of the case (both clinical and roentgenographic), a quiz with answers and discussion, and a set of references. Detailed comprehensive texts must by necessity be long and contain many references to
Statistical Properties of the Branch-Site Test of Positive Selection
Authors: Z. Yang, M. dos Reis
Journal: Molecular Biology and Evolution (2010)

The branch-site test is a likelihood ratio test to detect positive selection along prespecified lineages on a phylogeny that affects only a subset of codons in a protein-coding gene, with positive selection indicated by accelerated nonsynonymous substitutions (with ω = dN/dS > 1). This test may have more power than earlier methods, which average nucleotide substitution rates over sites in the protein and/or over branches on the tree. However, a few recent studies questioned the statistical basis of the test and claimed that the test generated too many false positives. In this paper, we examine the null distribution of the test and conduct a computer simulation to examine the false-positive rate and the power of the test. The results suggest that the asymptotic theory is reliable for typical data sets, and indeed in our simulations, the large-sample null distribution was reliable with as few as 20–50 codons in the alignment. We examined the impact of sequence length, the strength of positive selection, and the proportion of sites under positive selection on the power of the branch-site test. We found that the test was far more powerful in detecting episodic positive selection than branch-based tests, which average substitution rates over all codons in the gene and thus miss the signal when most codons are under strong selective constraint. Recent claims of statistical problems with the branch-site test are due to misinterpretations of simulation results. Our results, as well as previous simulation studies that have demonstrated the robustness of the test, suggest that the branch-site test may be a useful tool for detecting episodic positive selection and for generating biological hypotheses for mutation studies and functional analyses. The test is sensitive to sequence and alignment errors and caution should be exercised concerning its use when data quality is in doubt.
Hilar Adenopathy with Yersinia Infection
Authors: EERO SAIRANEN
Journal: Annals of Internal Medicine (1974)

Comments1 May 1974Hilar Adenopathy with Yersinia InfectionEERO SAIRANEN, M.D.EERO SAIRANEN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-80-5-673_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The principal point of the recent article by Winterbauer, Belic, and Moores (Ann Intern Med 78: 65-71, 1973) is that bilateral hilar adenopathy in association with erythema nodosum should be considered a priori evidence of sarcoidosis and that biopsy confirmation of the diagnosis is not necessary.The clinical features ofYersinia enterocoliticaorYersinia pseudotuberculosis[Pasteurella pseudotuberculosis] infections, such as septicaemia, gastroenteritis, mesenteric lymphadenitis or terminal ileitis resembling appendicitis, erythema nodosum, and arthritis, have been encountered increasingly in recent years in different parts of the world (1-5). In 1972 several studies (Table 1) also reported pulmonary changes,...References1. AHVONEN P: Human yersiniosis in Finland. I. Bacteriology and serology. II. Clinical features. Ann Clin Res 4:30-48, 1972 MedlineGoogle Scholar2. MOLLARET H: L'infection humaine a "Yersinia enterocolitica" en 1970, a la lumière de 642 cas récents. Aspects cliniques et perspectives épidémiologiques. Pathol Biol (Paris) 19:189-205, 1971 MedlineGoogle Scholar3. WINBLAD S: Yersiniainfektioner hos människan. Medicinsk Arbog 13:244-258, 1970 Google Scholar4. HÄLLSTRÖMSAIRANENOHELA KEK: A pilot clinical study on yersinioses in South-Eastern Finland. Acta Med Scand 191:485-491, 1972 MedlineGoogle Scholar5. SEGAARDLASSENSOLEM EJJ: Kliniske manifestasjoner av Yersinia enterocolitica-infeksjoner. En omtale av 20 egne kasus. Tidsskr Nor Laegeforen 92:1039-1041, 1972 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: EERO SAIRANEN, M.D.Affiliations: Etelä-Saimaa Central Hospital Lappeenranta, Finland PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySarcoidosis and yersinia enterocoliticaSuppurative lymphadenitis withYersinia enterocoliticaClinical Syndromes and Pathology in HumansUncommon acute bacterial pneumoniasFollow-up Studies of Joint Complications in Yersiniosis 1 May 1974Volume 80, Issue 5Page: 673-674KeywordsAppendicitisArthritisBiopsyErythemaGastroenteritisSarcoidosis ePublished: 1 December 2008 Issue Published: 1 May 1974 PDF downloadLoading ...
Regulation of hepatic transport of bile salt. Effect of protein synthesis inhibition on excretion of bile salts and their binding to liver surface membrane fractions.
Authors: M C Gonzalez, E Sutherland, F R Simon
Journal: Journal of Clinical Investigation (1979)

The overall transport of bile salts across the hepatocyte is characterized as a carrier-mediated process whose rate-limiting step is biliary secretion. Specific bile salt binding proteins have been identified in liver surface membrane fractions and were postulated to represent the initial interaction in bile salt translocation across both the sinusoidal and canalicular membranes. To test this hypothesis, cycloheximide was administered to rats to inhibit hepatic protein synthesis. 16 h after cycloheximide administration [14C]leucine incorporation into hepatic protein was inhibited by 93% at 1 h and 47% at 12 h. However, values of liver function tests were not increased, although serum albumin, serum alanine amino-transferase, and alkaline phosphatase were significantly decreased. Light and electron microscopy did not demonstrate necrosis or fat accumulation. The latter demonstrated minimal disorganization of rough endoplasmic reticulum and occasional lamellar whorls. 16 h after cycloheximide administration bile salt independent bile flow, basal bile salt excretion, and basal bile flow were unaltered, but the maximum bile salt transport capacity was reduced to 62% of control and 24 h later to 38%. Decreased bile salt transport was reversible, for it returned to control values after 48 h, when hepatic protein synthesis was also normal. Maximum bromosulfophthalein (BSP) transport, on the other hand, was reduced after 16 h to only 85% of control. Both bile salt and BPS maximum transport capacities decreased with time during inhibition of protein synthesis, apparently following first order kinetics. It was estimated that their half-lives are 20 h for bile salt transport and 55 h for BSP transport. These different turnover rates suggest that cycloheximide does not decrease active transport through generalized hepatic dysfunction or alteration of high energy sources possibly required for transport. The maximum number of [14C]cholic acid binding sites in liver surface membrane fractions was determined by an ultrafiltration assay. They were reduced to 68% of control after 16 h of cycloheximide and to 25% after 24 h. This reduction in the number of binding sites is apparently selective, for the activities of the liver surface membrane enzymes (Na+-K+)ATPase, Mg++-ATPase, and 5'-nucleotidase were not significantly changed. The associated alterations in bile salt transport and the maximum number of binding sites after cycloheximide administration suggests that these receptors may be the bile salt carriers.
Diagnosis and management of first trimester miscarriage
Authors: D. Jurkovic, C. Overton, R. Bender-Atik
Journal: BMJ (2013)

#### Summary points

Miscarriage is the most common complication of pregnancy. The reported rate of pregnancy loss in women with a missed menstrual period and positive urine pregnancy test is 12-24%.1 The true rate of miscarriage is probably higher because many losses occur preclinically, before a menstrual period is missed.2

About 125 000 miscarriages occur annually in the United Kingdom, resulting in 42 000 hospital admissions.3 Although miscarriages mostly resolve spontaneously without treatment and rarely cause severe maternal morbidity, the burden of disease is considerable, owing to the high incidence and associated costs of diagnostic investigations, hospital admission, surgical treatment, and follow-up. The loss of a pregnancy is often distressing for women and their partners, with adverse effects on their social and psychological wellbeing.

Reported UK maternal mortality rates after miscarriage in the period 1985 to 2008 range from 0.05 to 0.22 per 100 000 maternities.4 The most common causes of death were haemorrhage and sepsis, which tended to occur more often after second trimester losses.

Women with miscarriages are often treated conservatively in an outpatient setting, and general practitioners are often asked to advise women on the management options available to them and to provide support during follow-up. The aim of this review is to describe the diagnosis and …
RELATIONSHIP BETWEEN EFFECTS ARTERIAL ELASTANCE AND SPECIFIC MEASURES OF ARTERIAL PROPERTIES IN MIDDLE AGE: THE ASKLEPIOS STUDY
Authors: Julio A. Chirinos, Ernst R. Rietzschel, Marc L. De Buyzere, Tom Claessens, Dirk De Bacquer, Thierry C. Gillebert, Patrick Segers
Journal: Journal of the American College of Cardiology (2013)
Review of Child Development
Authors: Marjorie C. Meehan
Journal: JAMA (1967)

Probably most physicians would like to know and use the results of research on children's social and psychological development, but have not time to read the relevant literature. This book, carefully designed to summarize and integrate such material for the practicing professional, should help solve the problem. The editors, aided by an advisory committee which included a pediatrician, a psychiatrist, educators, and psychologists, selected 11 topics of wide interest, such as mental retardation, language development, juvenile delinquency. They then invited researchers in each field to write about their own and others' work, with special reference to the interests of the practitioner. Each chapter was then reviewed by another editorial consultant, to assure the adequate coverage of the field. The result of all this careful planning is a remarkably readable and authoritative book, free of most of the well-known faults of multi-authored works and summaries of "recent advances." From its title,
Pentazocine: Massive Dosage Without Side Effects
Authors: Joel Neuschatz
Journal: JAMA (1969)

<h3>To the Editor:—</h3> Medical research has continually sought a potent but non-narcotic analgesic agent. In the early part of this decade many morphine antagonists were screened for these attributes. From these studies, pentazocine (Talwin) emerged.<sup>1</sup>In early trials it was hailed for the effectiveness of its analgesic as well as its nonaddicting properties.<sup>2,3</sup>Thirty milligrams of pentazocine is considered to have the analgesic effect of 50 to 75 mg of meperidine or 10 mg of morphine.<sup>4,5</sup>Withdrawal symptoms have not been reported even after abrupt cessation in the face of months of therapy. Reports of overdosage are virtually nonexistent. Usual side effects include nausea, vomiting, and drowsiness. Respiratory depression has been reported. The usual recommended dosage for parenteral administration is 30 mg every three to four hours. The maximum suggested single dose is 60 mg. The following case is presented to demonstrate the margin of safety available