tbuckley/cabot-search huggingface dataset:
Treatment With Insulin and Its Analogs in Pregnancies Complicated by Diabetes
Authors: Lois Jovanovic, David J. Pettitt
Journal: Diabetes Care (2007)

Before the advent of insulin in 1922,  90% infant mortality rate and a 30% maternal mortality rate. As late as 1980, physicians were still counseling diabetic women to avoid pregnancy. This philosophy was justified because of the poor obstetric history in 30–50% of diabetic women. Improved infant mortality rates finally occurred after 1980, when treatment strategies stressed better control of maternal plasma glucose levels, once self-monitoring of blood glucose and A1C became available. As the pathophysiology of pregnancy complicated by diabetes has been elucidated and as management programs have achieved and maintained near-normoglycemia throughout pregnancy complicated by diabetes, perinatal mortality rates have decreased to levels seen in the general population (2–5). This review reports the literature on the safety and efficacy of insulin analogs in pregnancy and thereby enables the clinician to choose the optimal insulin treatment protocol to achieve and maintain normoglycemia throughout pregnancies complicated by diabetes.

Maternal glucose freely crosses the placenta. Maternal insulin does not cross the placenta unless it is bound to IgG antibody, which carries it through the placenta or insulin is forced through the placenta by high perfusion (6,7). Diabetic fetopathy is thought to be the result of fetal hyperinsulinemia (1–9). Thus, our treatment must be designed to normalize maternal blood glucose concentrations without the use of exogenous insulins that cross the placenta.

Placental transfer of insulin complexed with immunoglobulin has also been associated with fetal macrosomia in mothers with near-normal glycemic control during gestation. Menon et al. (8) reported that antibody-bound insulin transferred to the fetus was proportional to the concentration of antibody-bound …
-Enolase in blood plasma during open heart surgery
Authors: A. USUI, K. KATO, T. ABE, M. MURASE, M. TANAKA, E. TAKEUCHI
Journal: Cardiovascular Research (1989)

The enolase isoenzyme composed of the beta subunit (alpha beta or beta beta enolase) is distributed predominantly in the heart and skeletal muscles. To see whether it may be a useful indicator of myocardial damage, concentrations of beta-enolase (the beta subunit of enolase) were determined in serial blood samples taken from 18 patients who underwent mitral valve replacement, using a highly sensitive enzyme immunoassay method. They were compared with those of creatine kinase MB isoenzyme (CK-MB) in the same samples. The mean arterial beta-enolase concentration was 6.60 (SD 3.84) ng.ml-1 at the beginning of anaesthesia. It increased rapidly after reperfusion and rose to greater than 100 ng.ml-1 at 2 h post-reperfusion. It remained high until 12 h post-reperfusion, and then decreased slowly. The plasma beta-enolase concentrations were significantly higher in coronary sinus samples than in arterial samples in the early phase after reperfusion. Since plasma carbonic anhydrase III, which is known to be localised only in the skeletal muscle, did not increase during the surgery, we suggest that the major portion of the elevated plasma beta-enolase was derived from heart muscle. Plasma concentrations of beta-enolase increased as quickly as those of CK-MB after reperfusion. The CK-MB concentrations had returned to normal at 2 d but the beta-enolase concentrations remained elevated up to 7 d. These results show that the determination of beta-enolase in plasma may be useful for estimating myocardial damage during open heart surgery.
The “Research Misconception” and the SUPPORT Trial: Toward Evidence-Based Consensus
Authors: Dominic J. C. Wilkinson, Nicole Gerrand, Melinda Cruz, William Tarnow-Mordi
Journal: The American Journal of Bioethics (2013)

Critics of SUPPORT, including Macklin and Shepherd in this issue (2013), argue that its consent forms encouraged the “therapeutic misconception.” They allege that SUPPORT investigators blurred the ...
Lysosomal disruption preferentially targets acute myeloid leukemia cells and progenitors
Authors: Mahadeo A. Sukhai, Swayam Prabha, Rose Hurren, Angela C. Rutledge, Anna Y. Lee, Shrivani Sriskanthadevan, Hong Sun, Xiaoming Wang, Marko Skrtic, Ayesh Seneviratne, Maria Cusimano, Bozhena Jhas, Marcela Gronda, Neil MacLean, Eunice E. Cho, Paul A. Spagnuolo, Sumaiya Sharmeen, Marinella Gebbia, Malene Urbanus, Kolja Eppert, Dilan Dissanayake, Alexia Jonet, Alexandra Dassonville-Klimpt, Xiaoming Li, Alessandro Datti, Pamela S. Ohashi, Jeff Wrana, Ian Rogers, Pascal Sonnet, William Y. Ellis, Seth J. Corey, Connie Eaves, Mark D. Minden, Jean C.Y. Wang, John E. Dick, Corey Nislow, Guri Giaever, Aaron D. Schimmer
Journal: Journal of Clinical Investigation (2012)

Despite efforts to understand and treat acute myeloid leukemia (AML), there remains a need for more comprehensive therapies to prevent AML-associated relapses. To identify new therapeutic strategies for AML, we screened a library of on- and off-patent drugs and identified the antimalarial agent mefloquine as a compound that selectively kills AML cells and AML stem cells in a panel of leukemia cell lines and in mice. Using a yeast genome-wide functional screen for mefloquine sensitizers, we identified genes associated with the yeast vacuole, the homolog of the mammalian lysosome. Consistent with this, we determined that mefloquine disrupts lysosomes, directly permeabilizes the lysosome membrane, and releases cathepsins into the cytosol. Knockdown of the lysosomal membrane proteins LAMP1 and LAMP2 resulted in decreased cell viability, as did treatment of AML cells with known lysosome disrupters. Highlighting a potential therapeutic rationale for this strategy, leukemic cells had significantly larger lysosomes compared with normal cells, and leukemia-initiating cells overexpressed lysosomal biogenesis genes. These results demonstrate that lysosomal disruption preferentially targets AML cells and AML progenitor cells, providing a rationale for testing lysosomal disruption as a novel therapeutic strategy for AML.
Hypertension in the Elderly: Correction and Clarification
Authors: Maureen C. Hatch
Journal: JAMA (1995)

To the Editor.  —In their recent article on implications of randomized trials, Dr Mulrow and colleagues 1 include a meta-analysis of 13 trials involving elderly hypertensive patients. The relevant data on several different endpoints are presented graphically as a plot of odds ratios (ORs) with 95% confidence intervals (CIs) for each individual trial and for all trials combined (their Figure 1).  The use of visual plots of ORs and CIs has become increasingly common in reviews of the literature, for good reason, since the graphic approach is an efficient and effective means of conveying quantitative information. Unfortunately, in the article by Mulrow et al, the data were plotted on an arithmetic scale rather than appropriately on a logarithmic scale. Hence, they convey a misleading impression. On a log scale, the CI has the property of being symmetrical around the point estimate. 2 A log scale corrects for the fact that although
Laparoscopic Findings in Primary Sclerosing Cholangitis
Authors: F. Ikeda, K. Yamamoto, S. Fujioka, R. Okamoto, K. Yabushita, M. Miyake, N. Shimada, H. Kono, M. Nakamura, R. Terada, Y. Miyake, T. Tsuji
Journal: Endoscopy (2001)

Primary sclerosing cholangitis (PSC) is a cholestatic disease characterized by segmental narrowing and dilatation of bile ducts. Few studies have been performed on the laparoscopic findings associated with this disease, and the present study was intended to assess the usefulness of laparoscopy for the diagnosis and staging of PSC.Six patients were examined by laparoscopy with liver biopsy. Repeated laparoscopy was performed in three patients.Laparoscopy revealed coarse surface irregularity and discoloration. Surface irregularity was classified into four grades: smooth, shallowly depressed, undulated, and nodular. The affected area showed whitish yellow discoloration. The discolored area was demonstrated as a poorly stained area by intravenous injection of indocyanine green (ICG). Lobular markings became apparent because of the yellow color change in the portal tract, resulting in a leopardskin-like appearance. Lymph-vessel dilatation was seen in advanced stages. Repeated laparoscopy of a patient without treatment demonstrated a progression from a smooth surface to a shallow depression with leopardskin-like markings. On the other hand, the two patients treated with immunosuppressive agents showed improvement of liver swelling and disappearance of the leopardskin-like markings and lymph-vessel dilatation.Laparoscopy may provide useful information for the diagnosis and staging of PSC.
Association of Low-Dose Exposure to Persistent Organic Pollutants with Global DNA Hypomethylation in Healthy Koreans
Authors: Keon-Yeop Kim, Dong-Sun Kim, Sung-Kook Lee, In-Kyu Lee, Jung-Ho Kang, Yoon-Seok Chang, David R. Jacobs, Michael Steffes, Duk-Hee Lee
Journal: Environmental Health Perspectives (2009)

BackgroundGlobal DNA methylation levels have been reported to be inversely associated with blood levels of persistent organic pollutants (POPs), xenobiotics that accumulate in adipose tissue. Whether these associations extend to a population with much lower concentrations of POPs is not known.ObjectivesThis study was performed to examine whether low-dose exposure to POPs was associated with global DNA hypomethylation in Koreans.MethodsThe amount of global DNA hypomethylation was estimated by the percent 5-methyl-cytosine (%5-mC) in Alu and LINE-1 assays in 86 apparently healthy Koreans. Among various POPs, organochlorine (OC) pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenylethers (PBDEs) were measured.ResultsMost OC pesticides were inversely and significantly associated with %5-mC in the Alu assay, with correlation coefficients in the range −0.2 to −0.3 after adjusting for age, sex, body mass index, smoking, and alcohol. The strongest OC pesticide associations with %5-mC in the Alu assay were observed with oxychlordane, trans-nonachlor, and p,p′-dichlorodiphenyldichloroethylene. The correlation coefficient of age with %5-mC in the Alu assay was −0.24, similar to correlations of OC pesticides with %5-mC in the Alu assay. Most PCBs and PBDEs showed nonsignificant inverse trends with %5-mC in the Alu assay, but for some PCBs the U-shaped association was significant. On the other hand, POPs were not associated with %5-mC in the LINE-1 assay.ConclusionsWe found that low-dose exposure to POPs, in particular OC pesticides, was associated with global DNA hypomethylation in apparently healthy Koreans.
Endoscopic treatment of bleeding esophageal varices
Authors: A. Krag, S. Adamsen, F. Bendtsen
Journal: Endoscopy (2007)

We read with great interest the meta-analysis by Triantos et al. [1] on the role of sclerotherapy in the treatment of acute variceal bleeding in relation to vasoactive drugs and ligation. Regarding vasoactive drugs, the analysis confirmed the findings of other meta-analyses [2] [3]. However, regarding the role of ligation, the authors concluded, ”Sclerotherapy can remain a gold standard in variceal bleeding,” despite their having shown a significant difference in favor of ligation with respect to the control of bleeding. We believe that the conclusions contradict the results of their own and of previous meta-analyses [4] [5]. According to the Baveno IV consensus, ligation can be considered to be the first-choice or ”gold standard” treatment [6].
Short Stature
Authors: Barbara Linder
Journal: JAMA (1988)

<h3>SELECTED CASE</h3> THE PATIENT is a 12 3/12-year-old Colombian boy with growth hormone deficiency. He was the full-term product of twin gestation and was born by repeated cesarean section, without complication. His birth weight was 2.5 kg and his twin sister's was 2.3 kg. Early growth and development were normal; however, by the end of the first year of life, the patient's growth was lagging behind that of his twin. Workup in Colombia reportedly revealed a parasitic infection. After appropriate treatment, growth velocity increased transiently. By the age of 2 years, however, growth velocity had again declined and by the age of 3 years, the patient was reportedly 10 to 12 cm shorter than his twin sister. The mother is 167 cm tall, the father is 190 cm, and a 14-year-old sister was 172 cm at the time. This child was first seen at the National Institutes of Health, Bethesda,
TV: Science and the Swastika
Authors: P. Weindling
Journal: BMJ (2001)

Channel 4, Mondays at 9 pm, 19 March to 2 April

Nazi Germany spent vast resources on medical and biological research. Doctors were prominent in Auschwitz and in other killing centres. These films claim that the “Final Solution” was driven by a Nazi “biological revolution.” This leaves us with the unresolved questions of whether the Nazis slavishly followed the laws of genetics as then understood and practised, or—as Sir Richard Doll's recollections of cancer cells depicted as Jews suggest—that Nazism perverted and debased science. German medicine was experimentally oriented, and research consumed ever increasing resources. Yet after the war allied doctors concluded that its record of clinical innovation was poor and that release of the full story of Nazi human experiments would shake public confidence in clinical research.

These programmes present testimonies of victims who speak with …
More mutated genes involved in cancer than previously thought
Authors: Zosia Kmietowicz
Journal: BMJ (2007)

The number of abnormal or mutated genes that drive the development of malignant tumours is far greater than previously thought, according to the largest survey of cancer genes so far ( Nature 2007; 446:153-8, doi: 10.1038/nature05610).

Scientists at the Wellcome Trust Sanger Institute, where one third of the human genome was sequenced, have decoded parts of 500 genes from 200 individual cancers. The study looked at mutated genes within tumours. These mutations are not present in other tissues, and are not inherited.

It is known that 350 of the 25 000 or so genes in human DNA are implicated in the development of tumours. But to screen every gene within a tumour for genetic mutations would not be …
The site of action of Ptychodiscus brevis toxin within the parasympathetic axonal sodium channel h gate in airway smooth muscle
Authors: Sadahiro Asai, Joseph J. Krzanowski, Richard F. Lockey, Wayne H. Anderson, Dean F. Martin, James B. Polson, Samuel C. Bukantz, Andor Szentivanyi
Journal: Journal of Allergy and Clinical Immunology (1984)
Generalized Paresis in a 15-Year-Old Girl
Authors: Paul A. Greenberg
Journal: JAMA (1965)

GENERALIZED paresis of  insane and  late manifestations of congenital syphilis were at one time relatively common clinical problems. Today  remaining handful of patients with generalized paresis inhabit  back wards of state mental hospitals, and congenital syphilis is seen infrequently in newborns and almost never as  late onset form of  disease. With  discovery of penicillin, and  subsequent relative decline in  number of cases of syphilis being seen by  private practitioner, there has been a tendency to omit  serological test for syphilis from  routine prenatal examination.  In  past few years syphilis has been on  increase, particularly in  15- to 25-year-age group—the early reproductive years. It is by reputation the great imitator, and unless suspected and looked for, it will be missed. The occurrence of late-onset congenital syphilis manifesting itself as generalized paresis is a rare situation. This
Noninvasive Detection of Lentiviral-Mediated Choline Kinase Targeting in a Human Breast Cancer Xenograft
Authors: Balaji Krishnamachary, Kristine Glunde, Flonne Wildes, Noriko Mori, Tomoyo Takagi, Venu Raman, Zaver M. Bhujwalla
Journal: Cancer Research (2009)

Abstract Elevated phosphocholine (PC) and total choline (tCho) metabolites are widely established characteristics of most cancer cells, including breast cancer. Effective silencing of choline kinase (chk), the enzyme that converts choline to PC, is associated with reduced tumor growth. The functional importance and down-regulation of chk using RNA interference has been previously established. Here, we report on the preclinical evaluation of lentiviral vector–mediated down-regulation of chk using short hairpin RNA (shRNA) in established tumors derived from human breast cancer cells. Concentrated lentivirus expressing shRNA against chk was injected i.v. in the tail vein of MDA-MB-231 tumor-bearing female severe combined immunodeficient mice. Transduction efficiency in cells and tumors in vivo was assessed optically by enhanced green fluorescent protein expression and additionally from chk mRNA and protein levels. An 80% reduction in chk mRNA and protein was achieved following ∼90% transduction efficiency in cells. After transduction with chk-shRNA, 1H magnetic resonance spectroscopy (MRS) of cell and tumor extracts showed decreases in PC and tCho levels (P &amp;lt; 0.01 and 0.05, respectively) in comparison with controls. PC levels were monitored noninvasively by 31P MRS in tumors and by 1H MRS in cell and tumor tissue extracts. Noninvasive 31P MR spectra of chk-shRNA–transduced tumors in vivo showed lower PC and phosphomonoester levels that were associated with reduced tumor growth and proliferation. This study shows the use of lentiviral vectors to target chk in a human breast cancer xenograft and noninvasive MRS detection of this targeting. [Cancer Res 2009;69(8):3464–71]
THE McINTYRE ELEPHANTIASIS CASE.
Authors: G. LAIDLAW
Journal: JAMA (1896)

In this world of phenomena it is not strange that a physician and surgeon, practicing his profession for a number of years, should occasionally meet with pathologic conditions more or less rare, but it is strange that some should meet the most remarkable cases at every turn, so to speak. In this connection I am sure that it is the privilege of very few professional men, outside of very large hospitals, to deal with more extraordinary cases than have come to the notice and care of my much respected friend and colleague, C. J. McIntyre, C.M., M.D. As a partial proof of the foregoing assertions, I take great pleasure in presenting to the reader four different views of a patient whom the doctor has had for several years, together with a few brief remarks upon the history of this particular case and the disease with which the lady is afflicted.
Eosinophilic Granuloma
Authors: William J. Baker, John D. Houghton, Egon Wissing, Reeve H. Betts
Journal: New England Journal of Medicine (1948)

EOSINOPHILIC granuloma is a rare disease of bone that has only recently been described as an entity. Approximately 45 cases have been reported in the literature. The condition was simultaneously described in 1940 by Lichtenstein and Jaffe1 and by Otani and Ehrlich.2 The former employed the term "eosinophilic granuloma," and the latter "solitary granuloma of bone," to describe the same pathologic process. Otani and Ehrlich's term has largely been dropped, because the lesions are not always solitary and "eosinophilic granuloma" gives a connotation that adds specificity to the mental picture of the lesion. Two previous reports3 , 4 in the literature described . . .
Stress: The Hidden Adversary
Authors: Sara C. Charles
Journal: JAMA (1983)

In his foreword, the author states his intention of writing an introductory text on stress aimed principally at students in medicine, nursing, psychology, and the social sciences. Because all of us have experience with stress, it is a subject not only of abiding personal curiosity but of intricate complexity and broad application to the practice of medicine. It is therefore a subject that should be of interest to every physician.  The organization of the volume is well devised and logical. The nature and sources of stress, its relationship to the personality, especially one's self-concept, and the various psychological and physiological responses to stress are all progressively discussed. Stress as it relates to occupation, education, and adolescence provides additional subjects.  The overview of the basic material is presented in a simplistic and, in Dr Dobson's words, introductory manner. While the author has been painstaking in listing an almost obsessively extensive list
The Inhibitory Effect of Smoking on the Lower Esophageal Sphincter.
Authors: George W. Dennish
Journal: Annals of Internal Medicine (1971)

Meeting Abstracts1 May 1971The Inhibitory Effect of Smoking on the Lower Esophageal Sphincter.George W. Dennish, Donald O. CastellGeorge W. DennishSearch for more papers by this author, Donald O. CastellSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-5-834_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe primary function of the lower esophageal sphincter is to prevent reflux of gastric contents into the esophagus. Patients with symptomatic incompetence of this sphincter often complain of heartburn associated with smoking. This study investigated the relationship between smoking and pressure in the lower esophageal sphincter. A group of normal volunteer subjects were studied after an overnight fast. Using an infused, open-tipped recording system, pressure was monitored continuously in the lower esophageal sphincter for a 15-min basal period and for an additional 20 min after initiation of smoking two cigarettes consecutively. In each subject there was a rapid decrease in... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: George W. Dennish; Donald O. Castell PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byNovel therapies for gastroesophageal reflux diseaseStress-Related Nicotine Abuse and Disorders of the Gastrointestinal Tract 1 May 1971Volume 74, Issue 5Page: 834-834KeywordsEsophagus ePublished: 1 December 2008 Issue Published: 1 May 1971 PDF downloadLoading ...
The Lucky Rat
Authors: John R. Whittier
Journal: JAMA (1969)

<h3>To the Editor:—</h3> This is to compliment you on your publication of "The Lucky Rat" by Don T. Killderatt, MA, Chicago (<b>208</b>:1909, 1969). Having a long interest in the rat as an experimental animal, having employed it as such, having been consultant in neurology and psychiatry to the Bronx Zoo in years past, having present responsibility for a small animal colony numbering more than 200 or 300 rats, having studied a rare genetically determined strain of "hairless" rat, and finding myself presently in what may be described as an "interface" position between animal experimental and human experimental investigators and their subjects, I found this letter both informative and refreshing. I cannot avoid sharply questioningThe Journalwhether in view of the fact the author identified himself as a "simple physician and surgeon" the title following his name is compatible, namely "MA." Perhaps this is somehow contrasted with "complicated" ones?
Pregnancy after bariatric surgery does not affect weight loss
Authors: A. Alatishe, B. J. Ammori, A. A. Syed
Journal: BMJ (2012)

Maternal obesity increases the risk of pregnancy complications,1 2 3 4 and rates of adverse maternal and neonatal outcomes are lower after bariatric surgery.4 5 Although women are advised to avoid pregnancy for 12-24 months after bariatric surgery owing to fears of fetal undernutrition and reduced weight loss benefits,3 4 little …