tbuckley/cabot-search huggingface dataset:
Synthesis and activity of novel indole derivatives as inhibitors of CD38
Authors: Dongying Wu, Kaiyiu Ting, Yaokai Duan, Na Li, Jianguo Li, Liangren Zhang, Honcheung Lee, Lihe Zhang
Journal: Acta Pharmaceutica Sinica B (2013)

CD38 is a multifunctional enzyme/receptor expressed in a variety of mammalian tissues, regulating a wide range of physiological functions. Beginning with the previously reported compound 1, an inhibitor of human CD38 NADase, we synthesized a series of indole-based NH-substituted derivatives with modifications on alkyl chains, changes in substituent groups on aromatic rings, and differences in carbon chain lengths. Compounds 10, 13, 16 and 34 exhibited moderate inhibition of human CD38 NADase. Analysis of the structure-activity relationships showed that the phenylpropionyl moiety was very important for the inhibitory activity. This study provides information for the rational design of CD38 inhibitors.
Bearing Bad News
Authors: Richard H. Fine
Journal: Annals of Internal Medicine (1992)

Letters15 November 1992Bearing Bad NewsRichard H. Fine, MDRichard H. Fine, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-117-10-879_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors: I was very moved by Dr. Litwin's "Ode to Joy" (1) and at the same time was saddened by the failure of the attending physician to adequately prepare the intern to meet with the family. Thank God for the supportive nursing supervisor, Joy, who picked up the emotional pieces and taught the fledging intern how to communicate his caring to the patient's family.This failure is too often repeated in teaching hospitals. Housestaff and students are frequently asked to break bad news to patients and families without ever having this difficult role discussed or modeled for them...Reference1. Litwin J. Ode to joy. Ann Intern Med. 1992;117:337. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: University of California, San Francisco San Francisco General Hospital San Francisco, CA 94110 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 November 1992Volume 117, Issue 10Page: 879-879KeywordsEmotions Issue Published: 15 November 1992 PDF downloadLoading ...
The Medical Sciences Knowledge Profile Examination
Authors: Barry Stimmel
Journal: New England Journal of Medicine (1980)

Major changes in educational policy usually follow an evolutionary course. Some observers have cynically compared altering a medical-school curriculum to relocating a cemetery. At times, a proposal is rapidly implemented in response to external pressures; the most recent example is the implementation of the Visa Qualifying Examination in response to the Health Professions Educational Assistance Act of 1976.1 Changes from within a system occur more slowly. In 1973, the Committee on Goals and Priorities of the National Board of Medical Examiners (NBME) published a report recommending that a comprehensive qualifying examination be given at the end of four years of . . .
Pulmonary Edema Associated with Tocolytic Therapy
Authors: Richard J. Pisani
Journal: Annals of Internal Medicine (1989)

Purpose: To familiarize the general internist with the unique features of pulmonary edema occurring in association with tocolytic therapy (drugs used to inhibit uterine contractions). Data Identification: The literature in English was searched using MEDLINE (1966 to 1988), and bibliographies of pertinent articles and texts were reviewed. Study Selection: Fifty-eight case reports were examined by both authors and served as the database. Data Extraction: Several clinical variables, when available, were extracted from each case reported. Each variable was analyzed to provide an accurate composite description of pulmonary edema resulting from tocolytic therapy. Results of Data Synthesis: Patients with this syndrome present with dyspnea and may or may not have chest pain. Women at risk are receiving or have recently received sympathomimetic agents to arrest uterine contractions, with or without steroids. The incidence of the syndrome is higher in women with twin gestations. In postpartum cases, the syndrome usually occurs within 12 hours of delivery. Most women have intact membranes at presentation. Patients rarely have hypotension but usually have tachycardia and tachypnea. Chest roentgenograms usually show bilateral alveolar infiltrates and a normal-sized heart. Arterial blood gas values reveal an increased alveolar-arterial oxygen gradient. Hemodilution may cause a decrease in potassium values and the hematocrit. Patients respond rapidly to treatment with diuresis and oxygen administration and show clinical improvement usually within 24 hours. The underlying mechanism appears to be related to increased hydrostatic pressure and not to increased permeability of a direct toxic effect of tocolytic agents. Conclusions: Familiarity with the clinical features outlined above should increase the internist's ability to manage this problem without further invasive or noninvasive testing that might otherwise be used in evaluating dyspnea in pregnancy.
Words for Joy hut of Sorrow, the Year 1957
Authors: William B. Bean
Journal: JAMA (1962)

This book of verse, mostly melancholy, was published in England by the author who lives in Little Rock, Ark. He feels the poetic anguish of modern dehumanization, whether it be in medicine, war, or daily life, as mass man becomes characterized more and more by the shared lowest common denominator. The workmanship is not always sure, and the verses are uneven, though some are moving and give indication of suffering, frustration, and a clear perception of human needs. If you like bitter tea, this is your dish.
Disease activity in systemic lupus erythematosus related to a range of antibodies binding DNA and synthetic polynucleotides.
Authors: D A Isenberg, C Dudeney, W Williams, A Todd-Pokropek, B D Stollar
Journal: Annals of the Rheumatic Diseases (1988)

Antibodies to dDNA, nDNA, Z-DNA, poly(dT), poly(I), poly(dG.dC), poly(dA.dT), and total IgG and IgM were measured in five serial bleeds from 39 patients with systemic lupus erythematosus (SLE). The main findings were that those patients with renal disease form a distinct subset whose antibody levels correlate well with disease activity; anti-poly(dT) antibodies showed the best overall correlation with disease activity; and discriminant functional analysis demonstrated a major improvement in correlation of disease activity with combinations of antibodies to dDNA/nDNA/Z-DNA/poly(dT) (generally 50% or more were correctly classified) than with dDNA or nDNA alone (generally less than 25% correct). Serum IgG (but not IgM) correlated significantly (p less than 0.01) with six antibodies, suggesting that polyclonal activation plays a part in the development of these antibodies, though antibody cross reactivity is not excluded.
Corneal Sensitivity Is Reduced and Relates to the Severity of Neuropathy in Patients With Diabetes
Authors: Mitra Tavakoli, Panagiotis A. Kallinikos, Nathan Efron, Andrew J.M. Boulton, Rayaz A. Malik
Journal: Diabetes Care (2007)

Dr. Dash (1) has correctly identified potential confounders when measuring corneal sensitivity. Accordingly, exclusion criteria in our study were as follows: previous ophthalmic surgery affecting the cornea (including refractive surgery), previous ocular trauma, current use of topical ophthalmic medications, contact lens wear, chronic dry eye, or other ocular disease that …
Hereditary coproporphyria with acute intermittent manifestations.
Authors: H. D. Barnes, N. Whittaker
Journal: BMJ (1965)

Cytomegalovirus-Klemnola and Kaariaiinen *ME JRsH established during the disease in four previously healthy adults and one child with a mononucleosis-like disease without a positive heterophil agglutination test.No antibodies were demonstrable in the first sample from three patients.The disease was characterized by protracted fever and absence of tonsillitis.Enlargement of the lymph nodes was seen in only one patient.The tests for liver function gave abnormal results in all the cases.Leucocytosis, relative and absolute lymphocytosis, and the appearance of abundant atypical lymphocytes were features of the haernatological pattern.No significant rise of the C.F. antibody titre to the cyto- megalovirus was demonstrable in a single case among 19 patients suffering from infectious mononucleosis with a positive heterophil agglutination test or among 130 patients with various acute infectious diseases.A high titre, however, was found in two patients with infectious mononucleosis, there being a significant decrease of the titre later, after the disease was over, and in two patients of the control material, both of whom had a chronic debilitating disease in addition to their acute infection.
The Correlation between miRNA (miR: microribonucleic acid) Levels and Clinical Endpoints in Heart Failure
Authors: Ahmet Sayın, Burcu Zihni, Mustafa Beyazıt Alkan, Murat Bilgin, Berkir Serhat Yıldız, İlker Gül, Muhsin Özgür Çoğulu, Emin Karaca, Mehdi Zoghi
Journal: Journal of the American College of Cardiology (2013)
Electrolytes and Arterial Muscle Contractility
Authors: W. ALAN DODD, EDWIN E. DANIEL
Journal: Circulation Research (1960)

Arterial contractility in response to various drugs was studied in media designed to alter ionic gradients of sodium and potassium across the cell membrane. Tissues were analyzed to determine the effects of these procedures on tissue electrolytes and to demonstrate any correlation between tissue electrolytes and response. It was found that the contractile responses progressively decreased in sodium-free media, disappearing in 2 to 2½ hours. A decrease in external potassium, initially caused a potentiation of response. Thereafter, a decreased response was manifested, yet contractility remained even after 7 to 8 hours in potassium free medium. Increased external potassium caused an increase in response. There was no correlation between the content of sodium and potassium and response in potassium-free solutions, but in sodium-free solutions a positive correlation between contractility and potassium content existed. Chloride appeared to exist in 2 fractions, a diffusible fraction, and a more tightly bound fraction. Calculation of the ECFV based on the bound chloride yielded values which otherwise would have been absurd. Sodium appeared to be distributed in 3 fractions; diffusible and extracellular, not diffusible over the duration of our experiments and slowly diffusible and presumably intracellular, the latter fraction being possibly capable of cation exchange. Evidence obtained does not suggest that the sodium gradient, per se, is responsible for contractility. The concentration of intracellular potassium does not influence contractility directly. However, the potassium gradient may in part determine vascular muscle contractility.
Remember CURB BADLIP in the UK
Authors: M. Hoghton, S. Chadwick
Journal: BMJ (2010)

Minerva reported a bioethics memory aid to help doctors in the United States assess a patient’s capacity during an emergency.1 CURVES stands for choose and communicate, understand, reason, value, emergency, and surrogate.

In the United Kingdom, however, the law on making decisions about a person’s capacity is different from …
Principles of Laparoscopic Surgery: Basic and Advanced Techniques
Authors: Leo A. Gordon
Journal: JAMA (1995)

The first direct visual inspection of an internal organ (uterine cervix) appeared in the Babylonian Talmud (Niddah Treatise section 65b) in which a lead funnel with a bent mouthpiece equipped with a wooden drain pipe was introduced into the vagina.—Drs Sanfillipo and Lobe, chapter 26.1: "Principles of Pediatric Laparoscopy," p 451. ... in the course of a difficult biliary dissection where one does not really know where important structures are, the human surgeon could ask his machine partner to find the ducts ("Computer, show me the ducts please") using ultrasound, and then display their location on the stereoscopic heads-up display on which he is observing the operative field ("Also, computer, would you please color those ducts green... ").—Dr Michael Treat, chapter 38.6: "Surgical Robotics," p 843. There are three types of surgical text. The first is the innovator, the seminal text—a Shackelford, a Maingot, a Sabiston—a text that sets the standard
Acute Meprobamate Poisoning
Authors: Edwin H. Jenis
Journal: JAMA (1969)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
On the Feeding of Infants Deprived of Breast-Milk
Authors: G. Crichton
Journal: BMJ (1883)

tthe Worst b;ti&ci he Cer had, just onienterhg a firfstU&ss 'ial*ay c&Ariage; there was no other passenger, and, in, despair, be sdt dovh 'on the hot tin. in -an instant te pain *as gone; aMd sin6e t'eu, 'wIhe attackea, he flies to the fire and toasts him'self, or ajplies an India-rubber bag full' of hot water, with the test reu`lts.In conclusion, let me point to the fact that, in all these and similar p'ses, medical treatment is worthless; and that the sgrgeon alone t~aa effect a speedy,and radical cnre.I would, therefore, impress o,n V$&# tachers of surgery th e necessity of showing their class-pupils t6Ow, tb deal witth commcfn fections of the anus.The young'prkotl-'Vipber too frequently begins ,his professional career with a competent towledge of operations he may never be required to.perfoimnand '1i'total ignorance how to proceed in dealing with the simplest 'anid commonest affections requirilng operative skill.
Using email for abstracts submitted for conference was unexpectedly labour intensive
Authors: A W Murphy, M McSweeney, T C O'Dowd, G Bury, W Shannon, C P Bradley
Journal: BMJ (1998)

Prognosis of symptoms that are medically unexplained Every neurology service should have access to specialist liaison psychiatryEditor-Crimlisk et al's report on the outcome of motor symptoms that were medically unexplained in a cohort first identified at the National Hospital for Nervous Diseases is welcomed by those interested in the psychiatry of physical illness. 1 Slater's work, based on cohorts recruited in the 1950s, overestimated the likelihood of misdiagnosis in modern neurology, 2 and his conclusions have dissuaded psychiatrists from becoming involved in the management of hysteria.O'Brien's editorial on Crimlisk et al's study could have sounded two cautionary notes. 3Firstly, the study was not based on a true inception cohort, and it was recruited from a highly specialised centre.Usually, these factors lead to the finding of a worse prognosis than if only incident cases were included and the sample was less prone to recruitment bias.In this case, however, the bias may have been in the other direction.Patients seen at the National Hospital are likely to have been more exhaustively investigated and observed for longer (either in this episode or before referral) than they would be in most hospitals, so that the chances of misdiagnosis are reduced.We should not generalise the study findings to hospitals where initial assessment may be undertaken with little or no access to specialist neurological opinion or investigations.Secondly, the negative message-that high rates of undetected neurological disease are not seen at follow up-has been allowed to obscure the important positive findings of the study.Even years later, the patients had disabling physical symptoms and substantial psychiatric problems.As in Slater's original study, preventable deaths occurred from suicide and the complications of immobility.Many people were apparently not referred for psychiatric help either at the time of the initial presentation or subsequently.The important conclusion of Crimlisk et al's study must be that every neurology service should have easy access to referral to specialist liaison psychiatry. 4This group of patients, who are difficult to treat, are often resistant to treatment, and have a poor prognosis, may then have a reasonable chance of obtaining appropriate treatment for their primary disorder.
Co-delivery of siRNA and paclitaxel into cancer cells by biodegradable cationic micelles based on PDMAEMA–PCL–PDMAEMA triblock copolymers
Authors: Caihong Zhu, Sooyeon Jung, Sibin Luo, Fenghua Meng, Xiulin Zhu, Tae Gwan Park, Zhiyuan Zhong
Journal: Biomaterials (2009)
Coronary arteriography in a district general hospital: feasibility, safety, and diagnostic accuracy.
Authors: K Ranjadayalan, P G Mills, D C Sprigings, K Mourad, P Magee, A D Timmis
Journal: BMJ (1990)

To determine the feasibility, safety, and diagnostic accuracy of coronary arteriography in the radiology department of a district general hospital using conventional fluoroscopy and videotape recording.Observational study of the feasibility and safety of coronary arteriography in a district general hospital and analysis of its diagnostic accuracy by prospective within patient comparison of the video recordings with cinearteriograms obtained in a catheter laboratory.Radiology department of a district general hospital and the catheter laboratory of a cardiological referral centre.50 Patients with acute myocardial infarction treated with streptokinase who underwent coronary arteriography in a district general hospital three (two to five) days after admission. 45 Of these patients had repeat coronary arteriography after four (three to seven) days in the catheter laboratory of a cardiological referral centre.Incidence of complications associated with catheterisation and the sensitivity and specificity of video recordings in the district general hospital (judged by two experienced observers) for identifying the location and severity of coronary stenoses.Coronary arteriograms recorded on videotape in the district general hospital were obtained in 47 cases and apart from one episode of ventricular fibrilation (treated successfully by cardioversion) there were no complications of the procedure. 45 Patients were transferred for investigation in the catheter laboratory, providing 45 paired coronary arteriograms recorded on videotape and cine film. The specificity of the video recordings for identifying the location and severity of coronary stenoses was over 90%. Sensitivity, however, was lower and for one observer fell below 40% for lesions in the circumflex artery. A cardiothoracic surgeon judged that only nine of the 47 video recordings were adequate for assessing revascularisation requirements.Coronary arteriography in the radiology department of a district general hospital is safe and feasible. Nevertheless, the quality of image with conventional fluoroscopy and video film is inadequate and will need to be improved before coronary arteriography in this setting can be recommended.
Oncogene activation in spontaneous and chemically induced rodent tumors: implications for risk analysis.
Authors: S H Reynolds, S J Stowers, R M Patterson, R R Maronpot, M W Anderson
Journal: Environmental Health Perspectives (1988)

The validity of rodent tumor end points in assessing the potential hazards of chemical exposure to humans is a somewhat controversial but very important issue since most chemicals are classified as potentially hazardous to humans on the basis of long-term carcinogenesis studies in rodents. The ability to distinguish between genotoxic, cytotoxic, or receptor-mediated promotion effects of chemical treatment would aid in the interpretation of rodent carcinogenesis data. Activated oncogenes in spontaneously occurring and chemically induced rodent tumors were examined and compared as one approach to determine the mechanism by which chemical treatment caused an increased incidence of rodent tumors. Different patterns of activated oncogenes were found not only in spontaneous versus chemically induced mouse liver tumors but also in a variety of spontaneous rat tumors versus chemically induced rat lung tumors. In the absence of cytotoxic effects, it could be argued that the chemicals in question activated protooncogenes by a direct genotoxic mechanism. These results provided a basis for the analysis of activated oncogenes in spontaneous and chemically induced rodent tumors to provide information at a molecular level to aid in the extrapolation of rodent carcinogenesis data to human risk assessment.
Ionising radiation: three game-changing studies for imaging in sports medicine
Authors: Jessica Joan Orchard, John William Orchard, Trader Grenfell, Adam Mitchell
Journal: British Journal of Sports Medicine (2013)

It has been known for several years that there could be some cancer risk for young people from low-dose ionising radiation. With respect to diagnostic imaging, examinations such as nuclear medicine bone scans, CT, fluoroscopy and x-rays are all associated with exposure to ionising radiation.1 In 2001, Brenner et al 2 found that there was a significant increase in lifetime cancer risk attributable to radiation from paediatric CT scans relative to adult CT scans. The Image Gently Campaign by the Alliance for Radiation Safety in Paediatric Imaging has aimed to raise public awareness of ‘opportunities to promote radiation protection in the imaging of children’.3 It is thought that young people are at higher risk because cell division is fast and organs are therefore more sensitive to radiation at a younger age.4

Three landmark papers from Lancet 5 and BMJ 6 published in the past year have confirmed that the theoretical increased risk of cancer does bear out in follow-up studies. Pearce and colleagues’ study in Lancet looked at the excess risk of leukaemia and brain tumours for children and adolescents exposed to CTs. They found that children exposed to cumulative doses of 50 mGy (3–5 CTs) may have triple the risk of leukaemia, and doses of 60 mGy may have almost triple the risk of brain tumours.5 Though this appears to be a very large increase in risk, the authors point out that these cancers are still relatively rare, causing an estimated one excess case of leukaemia and one excess brain tumour per 10 000 head CTs. Moreover, although not specific to the discussion of paediatric patients, the lifetime cancer risk of developing …