tbuckley/cabot-search huggingface dataset:
Levothyroxine Therapy in Patients with Thyroid Disease
Authors: Susan J. Mandel
Journal: Annals of Internal Medicine (1993)

To review the indications for and the proper monitoring of levothyroxine therapy in patients with thyroid disease.Relevant English language articles published from 1966 to 1992 were identified through a MEDLINE search and manual searches of both identified articles and selected endocrinology texts.Studies, case reports, and review articles that contained data on the pathophysiologic aspects of relevant thyroid disorders and on the pharmacologic aspects of, indications for, and administration of levothyroxine therapy.Data on the epidemiology, clinical manifestations, complications, and treatment of thyroid disorders were analyzed with respect to patient selection, methods, diagnostic criteria, and conclusions. These data were used to develop a rational approach to the management of such patients.Levothyroxine is a reliable and commonly prescribed drug to treat thyroid disease, but excessive dosage may have adverse effects. In patients with hypothyroidism, levothyroxine is used as replacement therapy. For most patients, therapy can be initiated with a full replacement dosage (1.6 micrograms/kg body weight), which is usually 75 to 100 micrograms/day for women and 100 to 150 micrograms/d for men. The goal is to normalize the serum thyroid-stimulating hormone concentration. Levothyroxine is also used to suppress the serum thyroid-stimulating hormone concentration. A trial of thyroid-stimulating hormone suppressive therapy is indicated for most patients with benign solitary nonfunctioning thyroid nodules and for those with a history of thyroid cancer. Levothyroxine in non-thyroid-stimulating hormone-suppressive doses may also be indicated for patients with nontoxic multinodular goiter and for certain patients after lobectomy for benign thyroid nodules.With proper patient monitoring, levothyroxine replacement therapy should be effective, inexpensive, and free of complications. Recommendations for thyroid-stimulating hormone suppression with levothyroxine are based on risk-benefit considerations of the biologic characteristics of the thyroid disorder and the individual patient.
Influence of aliphatic alcohols on the hepatic response to halogenated olefins.
Authors: H H Cornish, M L Barth, B Ling
Journal: Environmental Health Perspectives (1977)

The role of alcohols in potentiating the toxicity of halogenated hydrocarbon solvents has been reviewed. The toxicity of carbon tetrachloride and chloroform can be markedly potentiated by prior treatment with ethanol or phenobarbital. Trichloroethylene toxicity may also be potentiated by ethanol ingestion. Prior ethanol ingestion acts by altering biochemical parameters that result in an increased response to subsequent solvent exposure. Simultaneous exposure to both ethanol and trichloroethylene allows for competitive substrate inhibition of metabolism since these compounds share several common enzymatic pathways. Thus the toxic response to multiple exposures varies depending upon the time sequence and the comparative levels of the individual components. Phenobarbital apparently potentiates solvent toxocity by induction of the microsomal mixed function oxidase system. Ethanol, either on a chronic or single dose basis, also has the ability to stimulate this enzyme system. Although alteration of the microsomal mixed function oxidase system by chronic ethanol ingestion may play an important role in potentiation of solvent toxicity, the potentiation seen following a single dose of ethanol cannot be fully accounted for by the known effects of ethanol on the mixed function oxidase system. In addition to ethanol a large number of other alcohols will markedly potentiate the hepatotoxic response to solvents such as carbon tetrachloride and chloroform. The mechanisms involved in such potentiation are not known at the present time.
The Imaging Viewpoint: How Imaging Affects Determination of Progression-Free Survival
Authors: Daniel Carl Sullivan, Lawrence H. Schwartz, Binsheng Zhao
Journal: Clinical Cancer Research (2013)

Abstract Tumor measurements on computed tomgoraphic or MRI scans and/or the appearance of new lesions on any of a variety of imaging studies including positron emission tomographic scans are key determinants for assessing progression-free survival as an endpoint in many clinical trials of therapies for solid tumors. Test–retest tumor measurement reproducibility may vary considerably across serial scans on the same patient unless rigorous attention is paid to standardization of image acquisition parameters and unless measurements are made by trained, experienced observers using validated objective methods. Target lesion selection also must be done with care to choose lesions that are or will be reproducibly measurable. Likewise, new lesions will be missed or misinterpreted on follow-up imaging studies unless those imaging studies are obtained using techniques suitable for detecting early, small lesions. Reader variability is clearly a major component of the problem. The increasing availability of semiautomatic image processing algorithms will help ameliorate that issue. In addition, an array of internationally accepted guidelines, standards, and accreditation programs now exist to help address these problems. Clin Cancer Res; 19(10); 2621–8. ©2013 AACR.
Dialyzable Currents of Injury in Potassium Intoxication Resembling Acute Myocardial Infarction or Pericarditis
Authors: HAROLD D. LEVINE, SIDNEY H. WANZER, JOHN P. MERRILL
Journal: Circulation (1956)

A byproduct of experience with the artificial kidney was the detection of reversible electrocardiographic "currents of injury" in patients with electrolyte imbalance. These changes occurred irrespective of anatomic alterations and resembled the changes of acute pericarditis or myocardial infarction. The electrolyte basis for the "current of injury" was established by the prompt abolition of the RS-T segment elevations, when the electrolyte imbalance was corrected by means of artificial hemodialysis.
TCT-542 False Lumen Thrombus Formation and Long-Term Outcomes in Type B Aortic Dissection
Authors: Keith Thompson, Armen Chalian, Ryan Clare, Albert Yuh-Jer Shen, Steven Khan, Michael Jorgensen, Vicken Aharonian, Kevin Patel, William A. Gray, Ajay J. Kirtane, Somjot Brar
Journal: Journal of the American College of Cardiology (2013)
THE TREATMENT OF PNEUMONIA
Authors: A. G. Newell
Journal: BMJ (1923)

tlhe plhlegm, and I had not a single death, from tuberculosis to record down to the year 1920.Moreover, I had one striking control case.A young boy was brought to us.Ee had positive physical signs at onie apex, an(i at the Lister Institute a few tubercle bacilli were founiid in his phlegm.We treated him for two months and he gabned.2lb. and improved very much.Unfortunately we notified the case.Thereupon a lay visitor went to the house and urged the mother to take the boy to Brompton Hospital.I lst sight of the boy for more thian a year, when the motlher told me the tragic story.At the instance of the lay visitor the boy went to Brompton and was six weeks in the hospital for observation.The mother was then told that the boy had not tuberculosis.(Tubercle bacilli hlad been found by us.)When I saw the boy again be was in a lhopeless third stage, and he died in a few months.Our diagnosis was tragically confirmed. .Thus ths only early case tlhat we were not allowed to treat died within two years; surely a striking control.These results obtained by me in England almost exactly tally withi thle results I lhave publishied in my book.3My records in Australia and London are quite good enough to give me unswerving faitlh in large doses of tuberculin given subcutaneously as easily tlle best remedy for tuberculosis in all its forms.
Informed Consent, Deception, and Discovering Drug Abuse
Authors: Quentin R. Regestein
Journal: JAMA (1992)

<h3>To the Editor.</h3> —Dr Bok<sup>1</sup>proposes that no matter how "unreasonable or socially unhelpful their choice may appear to the investigator," people have a right to refuse participation in research. She appeals to "codes of research ethics" that were drawn in response to Nazi horrors and other wrongdoings. But a drug abuser who refuses urine screening could be considered antisocial. It seems inconsistent to justify this antisocial refusal by appealing to codes that themselves try to prevent antisocial action. Bok might reply that society's interest warrants dissent. Nevertheless, society may also rightfully tax the individual. In fact, society may benefit more if it allows investigators to use deception to discover drug abuse than if it discourages them by requiring cumbersome methods of the sort Bok suggests. Some drug abusers might even welcome deceptive means to detect their otherwise uncontrollable habits as a step toward treatment. Similarly, they might disapprove
THE MEDICAL EXPERT WITNESS.Read before the McLean County Medical Society, Bloomington, Ill., Feb. 5, 1894.
Authors: JOHN A. STERLING
Journal: JAMA (1894)

The field of medical jurisprudence, by the necessities and conditions of the times has been enlarged, until it now assumes a phase of high importance to the profession, both of medicine and law. Its principles were applied in a primitive form centuries ago, but not until recent years has it developed into a science. It has made its present growth largely within the present century, and is now fully recognized by the general practitioner of both professions, as an indispensable part of his professional learning. This increased importance of the new science is due to two causes: 1. The science of medicine has been improved. Its rules and principles have been reduced to greatsr certainty; and the accuracy with which they have come to be administered, has firmly established the profession in the confidence of the people. This was absolutely necessary to render medical knowledge available for the purposes of
Supine Hypotension Syndrome During Cesarean Section
Authors: Gertie F. Marx
Journal: JAMA (1969)

Elective repeat cesarean section was scheduled for a 28-year-old woman, 39 weeks' pregnant. She had undergone her first section eight years ago for cephalopelvic disproportion and had had two subsequent transabdominal deliveries, the most recent 14 months ago. The antenatal course of this pregnancy was uneventful, and the patient's physical status was within normal limits. The patient was given atropine, 0.4 mg, preoperatively. On arrival in the operating room, she was lying comfortably on her back; blood pressure was 105/60 mm Hg; pulse rate, 92 beats per minute. An intravenous infusion was started and 800 ml of lactated Ringer's solution with dextrose were administered within 20 minutes. At this time blood pressure was 110/70 mm Hg and pulse rate, 88 beats per minute. A spinal block (8 mg tetracaine [Pontocaine]) was given with the patient in the lateral decubitus position. After the patient was returned to the supine position, blood
Bracing for the Impact of Expanded Second Amendment Rights
Authors: Julie D Cantor
Journal: New England Journal of Medicine (2010)

Otis McDonald thought he needed a gun. Not just any gun. Something more agile than his hunting shotguns. Something to deter the seedy element that had, over the years, infected his Chicago neighborhood with drugs and crime from threatening his life and breaking into his home yet again. He thought he needed a handgun. But city laws that effectively banned handgun possession by private citizens stood in his way. Two years ago, McDonald agreed to be the lead plaintiff in a case orchestrated to challenge those laws as violations of the Second Amendment. The lawsuit began the very day the . . .
Gamabufotalin, a bufadienolide compound from toad venom, suppresses COX-2 expression through targeting IKKβ/NF-κB signaling pathway in lung cancer cells
Authors: Zhenlong Yu, Wei Guo, Xiaochi Ma, Baojing Zhang, Peipei Dong, Lin Huang, Xiuli Wang, Chao Wang, Xiaokui Huo, Wendan Yu, Canhui Yi, Yao Xiao, Wenjing Yang, Yu Qin, Yuhui Yuan, Songshu Meng, Quentin Liu, Wuguo Deng
Journal: Molecular Cancer (2014)

Gamabufotalin (CS-6), a major bufadienolide of Chansu, has been used for cancer therapy due to its desirable metabolic stability and less adverse effect. However, the underlying mechanism of CS-6 involved in anti-tumor activity remains poorly understood.The biological functions of gamabufotalin (CS-6) were investigated by migration, colony formation and apoptosis assays in NSCLC cells. The nuclear localization and interaction between transcriptional co-activator p300 and NF-κB p50/p65 and their binding to COX-2 promoter were analyzed after treatment with CS-6. Molecular docking study was used to simulate the interaction of CS-6 with IKKβ. The in vivo anti-tumor efficacy of CS-6 was also analyzed in xenografts nude mice. Western blot was used to detect the protein expression level.Gamabufotalin (CS-6) strongly suppressed COX-2 expression by inhibiting the phosphorylation of IKKβ via targeting the ATP-binding site, thereby abrogating NF-κB binding and p300 recruitment to COX-2 promoter. In addition, CS-6 induced apoptosis by activating the cytochrome c and caspase-dependent apoptotic pathway. Moreover, CS-6 markedly down-regulated the protein levels of COX-2 and phosphorylated p65 NF-κB in tumor tissues of the xenograft mice, and inhibited tumor weight and size.Our study provides pharmacological evidence that CS-6 exhibits potential use in the treatment of COX-2-mediated diseases such as lung cancer.
Using Pharmacogene Polymorphism Panels to Detect Germline Pharmacodynamic Markers in Oncology
Authors: Daniel L. Hertz, Howard L. McLeod
Journal: Clinical Cancer Research (2014)

Abstract The patient (germline) genome can influence the pharmacokinetics and pharmacodynamics of cancer therapy. The field of pharmacogenetics (PGx) has primarily focused on genetic predictors of pharmacokinetics, largely ignoring pharmacodynamics, using a candidate approach to assess single-nucleotide polymorphisms (SNP) with known relevance to drug pharmacokinetics such as enzymes and transporters. A more comprehensive approach, the genome-wide association study, circumvents candidate selection but suffers because of the necessity for substantial statistical correction. Pharmacogene panels, which interrogate hundreds to thousands of SNPs in genes with known relevance to drug pharmacokinetics or pharmacodynamics, represent an attractive compromise between these approaches. Panels with defined or customizable SNP lists have been used to discover SNPs that predict pharmacokinetics or pharmacodynamics of cancer drugs, most of which await successful replication. PGx discovery, particularly for SNPs that influence drug pharmacodynamics, is limited by weaknesses in both genetic and phenotypic data. Selection of candidate SNPs for inclusion on pharmacogene panels is difficult because of limited understanding of biology and pharmacology. Phenotypes used in analyses have primarily been complex toxicities that are known to be multifactorial. A more measured approach, in which sensitive phenotypes are used in place of complex clinical outcomes, will improve the success rate of pharmacodynamics SNP discovery and ultimately enable identification of pharmacodynamics SNPs with meaningful effects on treatment outcomes. See all articles in this CCR Focus section, “Progress in Pharmacodynamic Endpoints.” Clin Cancer Res; 20(10); 2530–40. ©2014 AACR.
Does This Patient Have Appendicitis?
Authors: Ferris M. Hall
Journal: JAMA (1997)

<h3>To the Editor.</h3> —It is unfortunate that an article entitled "does this patient have appendicitis?" dismisses computed tomography (CT) with a single sentence stating that "the accuracy of computed tomography in diagnosing appendicitis has been inconsistent."1 Wagner et al<sup>1</sup>base this statement on references from an older literature, prior to the general availability of such improvements as spiral CT and thin section scanning. More recent studies demonstrate a 96% to 100% sensitivity and an 89% to 95% specificity of CT in the diagnosis of appendicitis.<sup>2-4</sup>Rao et al<sup>4</sup>identified the normal or abnormal appendix in all of their 100 cases. More importantly, CT can frequently diagnose or exclude other conditions that simulate appendicitis.<sup>2,3</sup> The article by Wagner et al<sup>1</sup>specifically emphasizes the clinical examination. As a radiologist who has spent much of his career writing about the overutilization of imaging examinations, I heartily concur with this approach. However,
Personalized Therapy for Acute Myeloid Leukemia
Authors: Christopher S. Hourigan, Judith E. Karp
Journal: Cancer Discovery (2013)

Abstract Summary: Patient-specific ex vivo drug sensitivity and resistance screening can identify rational drug candidates for the testing of personalized targeted therapy. An iterative approach of genomic and drug susceptibility characterization at sequential time points during clinical trials of targeted therapy in acute myeloid leukemia may be useful both for characterizing mechanisms of resistance and clonal evolution and also for identification of novel therapeutic targets and drug combinations. Cancer Discov; 3(12); 1336–8. ©2013 AACR. See related article by Pemovska et al., p. 1416
Tamoxifen and Breast Density in Women at Increased Risk of Breast Cancer
Authors: J. Cuzick, J. Warwick, E. Pinney, R. M. L. Warren, S. W. Duffy
Journal: JNCI Journal of the National Cancer Institute (2004)

Although mammographic breast density is associated with the risk of breast cancer and is influenced by hormone levels, the effects of tamoxifen on breast density in healthy women and whether tamoxifen-induced density changes are associated with breast cancer risk are unclear. We investigated mammographic breast density in healthy women with an increased risk of breast cancer at baseline and during 54 months of tamoxifen treatment.Mammograms were reviewed from 818 breast cancer-free women (388 in the tamoxifen group and 430 in the placebo group) at high risk for breast cancer, from the International Breast Cancer Intervention Study I, a trial of tamoxifen for breast cancer prevention. Breast density measurements, at baseline and during treatment, were obtained at 12- to 18-month intervals. Multivariable analysis was used to assess associations with breast density. All statistical tests were two-sided.Breast density at baseline was similar in placebo (42.6%, 95% confidence interval [CI] = 39.6% to 45.6%) and tamoxifen (41.9%, 95% CI = 38.8% to 45.0%) groups. The main determinants of breast density at baseline were age, menopausal status, body mass index, and previous atypical hyperplasia. A greater density reduction in the tamoxifen group (7.9%, 95% CI = 6.9% to 8.9%) than in the placebo group (3.5%, 95% CI = 2.7% to 4.3%) was apparent within 18 months of treatment (P<.001); the reduction in density continued until 54 months of treatment. After 54 months of tamoxifen treatment, breast density was 28.2% (decrease from baseline = 13.7%, 95% CI = 12.3% to 15.1%; P<.001) in the tamoxifen group and 35.3% (decrease from baseline = 7.3%, 95% CI = 6.1% to 8.4%; P<.001) in the placebo group. The tamoxifen-associated density reduction was apparent in all subgroups, but there was a statistically significant interaction with age. In women aged 45 years or younger at entry, the net reduction with tamoxifen was 13.4% (95% CI = 8.6% to 18.1%), whereas in women older than 55 years, it was 1.1% (95% CI = -3.0% to 5.1%).Tamoxifen treatment was associated with reduction in breast density, most of which occurred during the first 18 months of treatment.
Ischemic Response to Sudden Strenuous Exercise in Healthy Men
Authors: R. JAMES BARNARD, REX MACALPIN, ALBERT A. KATTUS, GERALD D. BUCKBERG
Journal: Circulation (1973)

In ten healthy, asymptomatic men, intra-arterial pressure and electrocardiograms were recorded during various types of exercise. Potential subendocardial blood flow was estimated from a diastolic pressure time index (DPTI) and myocardial oxygen requirements estimated from the tension time index (TTI). The ratio DPTI/TTI provided an estimate of the supply/demand relationship With sudden vigorous exercise without warm-up, the DPTI/TTI was below 0.35 in three men who had ischemic electrocardiograms, below 0.44 in three men with minor ST abnormalities, and above 0.44 in four men with normal ST segments. With a prior warm-up exercise, sudden exercise caused no ischemic changes, but DPTI/TTI was below 0.44 in two subjects who had minor ST abnormalities. Maximum treadmill testing produced higher heart rates and TTI than did sudden exercise, but DPTI/TTI was above 0.44 in all cases and no ST abnormalities occurred. Abnormal electrocardiographic responses produced by sudden, vigorous exercise in normal men may represent subendocardial ischemia caused by a transient, unfavorable alteration in the subendocardial oxygen supply/demand relationship which is predictable from arterial pressure measurements.
The Present Status of the Ketogenic Diet
Authors: D. SCHUYLER PULFORD
Journal: Annals of Internal Medicine (1932)

Excerpt It is my purpose to outline the present status of the ketogenic diet rather than urge its use or disprove its value by reporting results on 75 treated cases of epilepsy. Sufficient time has now elapsed since Wilder's1 introduction of this low carbohydrate high fat diet in 1921 to estimate its worth. Ketosis is physiologically different from acidosis caused by a shift in acid base equilibrium and has other effects than dehydration. Therefore, in spite of the brilliant results of Fay2 and McQuarrie3 and their followers with fluid restriction, diet-produced ketosis still commands our attention. EPILEPSY A SYMPTOM NOT A
Elements of graph design. By Stephen M. Kosslyn. 309 pp. New York: Freeman, 1994. $18.95
Authors: Raymond S. Koff
Journal: Hepatology (1995)

This work, now in its third edition, is designed to address a specific problem for those of us interested in the liver, namely, the widening gap between the bench researchers and the clinicians.Attempting to bridge this gap is a tall order, and this is a big book, costing $26 per pound, with contributions from 165 distinguished authors from around the globe.Only half of the authors have MD degrees, and little effort is made to adjust the level of the discussion for the clinician's benefit.Basic biomedical scientists will be comfortable with the high level of data presentation and interpretation, clinicians less so.This is not a book to be read on an airplane or on the beach.But, it is well worth the effort invested because it opens a window into the exciting and expanding world of basic research in the liver.In many instances, the result is pure elegance.The discussions on heme biosynthesis and porphyrin metabolism, alcohol, and iron are excellent.The chapters on lipoproteins and bile acids are the lucid discussions to be expected from established investigators in the field.The chapters on hepatic encephalopathy and portal hypertension are typical for this book, containing a balanced, in-depth discussion of all of the currently proposed mechanisms, with extensive references.Problems with each postulated mechanism are also included, and these chapters should be required reading for any researcher contemplating entry into this field.Many contributors have been enormously successful in communicating to the reader their palpable excitement about the new developments in their areas of expertise.For example, the chapter on immune mechanisms in viral hepatitis by Ferrari and Chisari and that on molecular aspects of autoimmune disease by Mackay are fascinating.As a rule, the illustrations function well to explicate the points being discussed.The chapter on energy metabolism by Seifter and Englard reads like a page-turner, amply fulfilling its aim