tbuckley/cabot-search huggingface dataset:
Research Proposals: A Guide to Success
Authors: Nathaniel I. Berlin
Journal: JAMA (1991)

The author is a veteran investigator whose career as a scientist includes participation in the National Institutes of Health (NIH) member study section, associate deanship at the University of Southern California, and directing research development at the Doheny Eye Institute. Such experiences have caused him to recognize the need for a no-nonsense, straightforward set of instructions on how to prepare an NIH research grant. Today, when medical research funding is said to be in a crisis, when only a small fraction of NIH grant applications are funded, and when a career in biomedical research is much less attractive to young people, this is a much-needed text. Dr Ogden's theme can be expressed in the terms of form and substance. Good science—substance—can be hampered in the review process by a poorly prepared proposal—form. Poor or ordinary science cannot be helped. Thus, how to put one's best foot forward is the theme.
Medicine, the Novel, and the Passage of Time
Authors: Rita Charon
Journal: Annals of Internal Medicine (2000)

Doctors and patients move together through time, humble in the face of its dictates. Novelists allow their characters to enter time, revealing in the characters' particular, ongoing lives some universal truths about living. Both the medical chart and the novel capture individual human lives as they change and as they age, finding some meaning in the random events that happen in them. Literary critics who write about the novel provide useful frameworks for doctors who reflect on their practice. In this essay, I examine the medical charts of two of my patients in detail and describe the experiences I shared with them. As a repository of detail not only about the patients but about the doctors and nurses who cared for them, the charts provide rich and powerful evidence about the insides of practice and the meanings that clinical relationships accrue. Doctors might discover underlying meaning in their practices that would otherwise elude them by reading their patients' charts as if they were novels, looking for patterns and movements throughout a patient's life, and recognizing the deep connections woven between their patients and themselves. By placing great novels—by Henry James, Virginia Woolf, and Thomas Mann—side by side with actual medical charts, I suggest the usefulness of close readings of medicine's texts. The juxtaposition suggests the utility of brooding about the seasons of our relationships with patients. Perhaps not a luxury but a necessity for effective care, reflection such as this on our patients may restore to medicine some of its passion, its meaning, and its joy.
Successful treatment of a giant exposed blood vessel in a gastric ulcer by endoscopic sclerotherapy with N-butyl-2-cyanoacrylate
Authors: K. Kurokohchi, T. Maeta, T. Ohgi, M. Ono, A. Yoshitake, T. Yachida, M. Yoshida, Y. Mori, F. Kohi, S. Kuriyama
Journal: Endoscopy (2007)

An 80-year-old man was admitted with hematemesis. Endoscopic examination revealed a deep giant gastric ulcer, and bleeding from the exposed blood vessel was detected in the lesser curvature of the angles of the stomach (Figure [1] a). We thought that only the navel-like region in the center of the ulcer was an exposed blood vessel, and ethanol was injected into the edge of this region (Figure [1] b). However, after the needle was removed, pulsatile bleeding began from the injection point (Figure [1] c), revealing that the wider area around the navel-like region was also part of the giant exposed blood vessel, which measured 10 mm (using biopsy forceps).
General practitioners and necropsies
Authors: K B Thomas, R O Weller
Journal: BMJ (1994)

The clinical picture during life and necropsy findings are two sides of the same coin. To look at one without the other is to see only half the picture. Proof of that assertion comes from the known discrepancy between the clinical and necropsy findings - for example, Cameron et al found that 15% of the main diagnoses and 42% of causes of death were not confirmed at necropsy and Hartveit reported that one in five diagnoses thought to be certain were found to be erroneous.1, 2

In this issue Berlin et al report that only 20% of deaths in the community are followed by necropsies and that three quarters of those are requested by coroners …
APPARATUS LEAK AS A CAUSE OF FALSE LOW BASAL METABOLISM READINGS
Authors: Kenneth M. Lynch
Journal: JAMA (1922)

<h3>To the Editor:</h3> —Basal metabolism determinations having become of the widest clinical use, it is well for all concerned in the performance of the test to be informed about every pitfall which may be encountered. As a general proposition, whenever a leak occurs in the apparatus used for the test, it will give an apparent increase in oxygen consumption, and consequently a false positive reading. This is, apparently, because a certain degree of positive pressure in the machine is developed by each exhalation, a certain amount of air being forced out at each respiration; whereas, inhalation does not create a negative pressure sufficient to cause the same amount of intake through the leak. The variation from the true consumption of oxygen is dependent on the amount of air escaping through the leak. Usually the presence of a leak in the apparatus is easily determined, and no test should be performed
A Lesson from the Third Year
Authors: Eric Helms
Journal: Annals of Internal Medicine (2004)

On Being a Doctor2 November 2004A Lesson from the Third YearEric Helms, MDEric Helms, MDFrom Mountain Area Health Education Center, Asheville, NC 28801.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-141-9-200411020-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail During my medicine clerkship, I had the privilege of caring for a man whose case brought up many questions and dilemmas in my mind. Mr. L. was a 70-year-old Chinese man who spoke only Cantonese, but in a dialect that most translators found incomprehensible. He apparently had no family and was in this country illegally. He lived with a group of other Chinese people, all of whom worked for a restaurant and lived with the owners. It was questionable whether Mr. L. had ever seen a western doctor before. He presented to the emergency department with severe abdominal pain, having ... Author, Article, and Disclosure InformationAffiliations: From Mountain Area Health Education Center, Asheville, NC 28801.Current Author Address: Eric Helms, MD, Mountain Area Health Education Center, 93 Victoria Road, Asheville, NC 28801; e-mail, [email protected]ncahec.org. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoBringing Professionalism to the Bedside Christine Laine and Harold C. Sox Professionalism and the Medical Student Charles K. Francis Professionalism and the Medical Student Nancy R. Angoff Metrics Cited byProfessionalism and the Medical StudentNancy R. Angoff, MD, MPH, MEdBringing Professionalism to the BedsideChristine Laine, MD, MPH, Senior Deputy Editor and Harold C. Sox, MD, EditorProfessionalism and the Medical StudentCharles K. Francis, MD 2 November 2004Volume 141, Issue 9Page: 736KeywordsEmergency departmentForecastingHeartHospital medicineHospitalsKidneysMedical dialysisNursing homesQuality of lifeRenal failure ePublished: 2 November 2004 Issue Published: 2 November 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 208: Low-dose actinomycin D decreases Mcl-1 expression and acts synergistically with ABT-737 to induce apoptosis of SCLC cell lines
Authors: Haishan Xu, Malika Humphries, Geoffrey W. Krystal
Journal: Cancer Research (2010)

Abstract SCLC is initially a highly chemotherapy-responsive disease but relapse and progressive development of chemotherapy resistance is the rule. Overexpression of pro-survival members of the Bcl-2 family, including Bcl-2, Bcl-XL and Mcl-1 are thought to play a role in the pathogenesis and chemotherapy resistance of SCLC. ABT-737, a BH3-mimetic drug which blocks the function of Bcl-2 and Bcl-XL, has shown single agent activity in preclinical models of SCLC and enhances the activity of a variety of cytotoxic agents. Low levels of Mcl-1 expression and high levels of Noxa expression have been characterized as markers of sensitivity to ABT-737 in SCLC and other malignancies. We have also noted that Noxa-mediated downregulation of Mcl-1 expression is absent in 4/4 SCLC cell lines examined, suggesting roles for this defect in the pathogenesis of SCLC and in resistance to ABT-737. Because of the short half-life of Mcl-1 mRNA and protein, we studied the effects of combining ABT-737 and actinomycin D, a general transcriptional inhibitor used in the treatment of Wilms tumor, sarcomas, germ cell and trophoblastic tumors. Actinomycin D decreased Mcl-1 expression in a dose-dependent fashion in the low ng/ml range, 3 logs lower than that required for general transcriptional inhibition. While exposure to actinomycin resulted in a cell line-dependent increase in Noxa expression, Noxa was not required for the decrease in Mcl-1 expression, as it occurred in the H209 cell line, which does not express Noxa, as well as the H69, WBA and H526 cell lines which do. Concentrations of actinomycin D from 0.4-4 ng/ml showed single agent activity across a panel of SCLC cell lines in 72 hr MTT viability assays and specifically induced a high grade G2-M cell cycle blockade. When combined with low micromolar doses of ABT-737, near complete loss of viability was seen with combination indices in the 0.5 range, indicating synergy by Chou-Talalay analysis, without a significant effect on MRC-5 pulmonary fibroblasts. In addition to loss of Mcl-1 expression and enhanced Noxa expression, correlates of apoptosis induced by the combination included marked Bid cleavage. Exposure to 4 ng/ml actinomycin was only required for the first 24 hrs of the combined incubation but the presence of ABT-737 was required for the full 72 hrs to see maximum loss of viability and clonogenic potential. This actinomycin exposure mimics a clinically achievable AUC of 100 ng.hr/ml after bolus administration, suggesting the feasibility of combination studies utilizing bolus actinomycin D administration. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 208.
Case 39-1962
Authors: John W. Raker, Austin L. Vickery
Journal: New England Journal of Medicine (1962)

Presentation of CaseA forty-three-year-old man was referred to the hospital because of pain in the abdomen.Five days previously the patient suddenly experienced severe, generalized abdominal pain two hours after a meal. The pain subsequently became localized to the right upper quadrant of the abdomen, with radiation to the right scapula and with moderate pain in the region of the right costovertebral angle. The pain was constant and unrelenting, was unaccompanied by nausea or vomiting and was relieved by an injection of an analgesic drug. Intermittent pain and marked anorexia occurred for two days, and he was admitted to . . .
The Scientific Name of the Spotted-Fever Tick
Authors: Nathan Banks
Journal: JAMA (1910)

To the Editor:—  In many of the publications on the spotted or Rocky Mountain fever, the tick is referred to asDermacentor occidentalis. This, I believe, is due to an identification of Dr. Stiles, following Neumann, who included it under that species. It is notDermacentor occidentalis. Dr. Stiles, in a paper on this disease in 1905, mentions in two places the nameDermacentor andersoni; he furnishes no figure and not a word of description, so that the name cannot, according to the rules of zoologic nomenclature, hold from that date. On June 6, 1908, a revision of the classification of the ticks of the United States was published by me in a bulletin of the Department of Agriculture. In this I described the spotted fever tick asDermacentor venustus n. sp. On July 3, 1908, Dr. Stiles, in a report of the Public Health and Marine-Hospital Service, gave some
Induction of heme oxygenase-1 inhibits the monocyte transmigration induced by mildly oxidized LDL.
Authors: K Ishikawa, M Navab, N Leitinger, A M Fogelman, A J Lusis
Journal: Journal of Clinical Investigation (1997)

Heme catabolic processes produce the antioxidants biliverdin and bilirubin, as well as the potent prooxidant free iron. Since these products have opposing effects on oxidative stress, it is not clear whether heme catabolism promotes or inhibits inflammatory processes, including atherosclerotic lesion formation. Heme oxygenase (HO) catalyzes the rate-limiting step of heme catabolism. We used cocultures of human aortic endothelial cells and smooth muscle cells to examine the possible role of HO in early atherosclerosis. Heme oxygenase-1 (HO-1), the inducible isoform of HO, was highly induced by mildly oxidized LDL, and augmented induction was observed with hemin pretreatment. This augmented HO-1 induction resulted in the reduction of monocyte chemotaxis in response to LDL oxidation. Conversely, inhibition of HO by a specific inhibitor, Sn-protoporphyrin IX, enhanced chemotaxis. Furthermore, pretreatment with biliverdin or bilirubin, the products of HO, reduced chemotaxis. Oxidized phospholipids in the mildly oxidized LDL appear to be responsible for HO-1 induction, since oxidized but not native arachidonic acid-containing phospholipids also induced HO-1. These results suggest that HO-1 induced by mildly oxidized LDL may protect against the induction of inflammatory responses in artery wall cells through the production of the antioxidants biliverdin and bilirubin.
AN IMMUNIZING SUBINFECTION IN SCARLATINA
Authors: A. D. Edwards
Journal: BMJ (1910)

APRIL 30, 1910I poly;norphonuclear cells.No tubercle bacilli were to be found.On November-20th, there being still no improvement, 10 c.cm. antimeningococal serum were injected hypodermically, the dose being repeated on November 23rd, 26th, and 27th, and on December lst respectLvely.No definite improvement was apparent until after the last injection, when the temperature began to fall rapidly, consciousness returned, and all the serious symptoms abated.This satisfactory condition of things cotluued,for five days, and then a relapse occurred, lasting for a-furtber period of five days, during which the old symptoms were revived, though less acutely, with the temperature again shooting up to 1030 F. It was then decided to inject 10 c.cm. antimeningococcl serum into the spinal canal, but an unex- pected amelioration in the child's condition prevented this intention being carried into effeet.From this-time on recovery w&s uninterrupted, and here you see the boy apparently as well and healthy as he ever was.On January 5,th another lumbar puncture for confirmatory purposes was done.The spinal fluid was then found to issue undter a much diminished pressure; when centrifugalized the deposit contained a few blood discs but-no axcssof leucocytes and no micro-organisms, and media inoculated with the deposit revealed no growth of the Dipploowows.intracellularis..I show you here the small flasks of antimeningococcal seum as they are sent out from the laboratory ready for use.Each flask contains 10 c.cm.We propose to inoculate the child we have examnined this afternoon, in the first place hypodermically, and later on, if need be, by the in-traspinal method.It may be mentioned that in eases of tubercalous meningitis the fluid withdrawn by lumbar puncture, though turbid, is often sterile, but on centrifugalization tabercle bacilli can generally be demonstrated in the residue.'The prevailing lymphocytes are of the small mononuclear type.In suppurative cases the polymorphonuclear cells are in abupdance, and the finding of the streptococcus, staphylococcus, pneumococcus, or other micro-organism it.the ebutrifugalized residue affords confirmatory evi- denee .of the type of meningi-tis which is under observation.
Well-Water Consumption and Parkinson’s Disease in Rural California
Authors: Nicole M. Gatto, Myles Cockburn, Jeff Bronstein, Angelika D. Manthripragada, Beate Ritz
Journal: Environmental Health Perspectives (2009)

Investigators have hypothesized that consuming pesticide-contaminated well water plays a role in Parkinson's disease (PD), and several previous epidemiologic studies support this hypothesis.We investigated whether consuming water from private wells located in areas with documented historical pesticide use was associated with an increased risk of PD.We employed a geographic information system (GIS)-based model to estimate potential well-water contamination from agricultural pesticides among 368 cases and 341 population controls enrolled in the Parkinson's Environment and Genes Study (PEG). We separately examined 6 pesticides (diazinon, chlorpyrifos, propargite, paraquat, dimethoate, and methomyl) from among 26 chemicals selected for their potential to pollute groundwater or for their interest in PD, and because at least 10% of our population was exposed to them.Cases were more likely to have consumed private well water and to have consumed it on average 4.3 years longer than controls (p = 0.02). High levels of possible well-water contamination with methomyl [odds ratio (OR) = 1.67; 95% confidence interval (CI), 1.00-2.78]), chlorpyrifos (OR = 1.87; 95% CI, 1.05-3.31), and propargite (OR = 1.92; 95% CI, 1.15-3.20) resulted in approximately 70-90% increases in relative risk of PD. Adjusting for ambient pesticide exposures only slightly attenuated these increases. Exposure to a higher number of water-soluble pesticides and organophosphate pesticides also increased the relative risk of PD.Our study, the first to use agricultural pesticide application records, adds evidence that consuming well water presumably contaminated with pesticides may play a role in the etiology of PD.
Abstract 2491: Biphasic effect of psoralidin on cell cycle regulatory markers in hormone refractory prostate cancer
Authors: Srinivas Koduru, Jurgen Rohr, Chendil Damodaran
Journal: Cancer Research (2010)

Abstract Cell cycle deregulation has been strongly associated with the pathogenesis of prostate cancer (PCa). Overexpression of cell cycle regulatory proteins (cyclin D1-25%, cyclin A-35% and cyclin B-75%) have been reported in clinical PCa samples when compared to normal prostate tissue. Based on this, we rationalized that downregulation of cell cycle regulatory molecules may play an important role in chemoprevention/therapy of PCa. We previously published that psoralidin; a natural compound effectively suppresses PCa growth both in vitro and in vivo. Hence, in this study we determined whether psoralidin alters cell cycle regulatory proteins in PCa cells. To determine this we performed cell cycle analysis using PI staining and also studied the expression patterns and activity of various cell cycle regulatory markers using Western blot analysis and kinase assays respectively in two hormone refractory prostate cancer (HRPC) cells (PC-3 and DU-145) following treatment with or without psoralidin in dose dependent manner. Psoralidin has biphasic effect on PCa cells where at a lower concentration (40µM) caused a G0/G1 cell cycle arrest whereas at a higher concentration (60µM) caused a G2/M cell cycle arrest. Psoralidin at lower concentration induced expression of cyclin dependent kinase inhibitors (p27, p57, p21, p16) in PC-3 and DU-145 cells whereas at higher concentration upregulation of p18 was observed in both HRPC cells. Additionally, we found that at lower concentration cyclins (E &amp; E2 and H) and cdks (6 and 9) are downregulated whereas at higher concentration psoralidin downregulated expression of cyclins (D1, A, E &amp; E2, B1, D3 and H) and cdks (6, 7, 2 and 9) in both HRPC cells. At lower concentration psoralidin inhibits expression of cdc-2 and cdc-25B whereas at higher concentration cdc-2, −25A and −25B are downregulated in both PC-3 and DU-145 cells. Also, psoralidin inhibited phosphorylation of Rb at both lower and higher concentration in HRPC cells causing irreversible cell cycle arrest resulting in the induction of apoptosis. These results clearly highlight the potential of psoralidin as a therapeutic agent for PCa. Currently, we are investigating the effect of psoralidin on cell cycle markers using both xenograft and TRAMP models. The outcome of our study may enable bringing psoralidin to the mainstream of medicine for prevention and/or therapy for PCa. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2491.
The Residual Lesion in Pulmonary Tuberculosis Requiring Surgery
Authors: Irving Kass, Terumasa Miyamoto, John Denst, George J. Wittenstein, William F. Russell, Gardner Middlebrook, Sidney H. Dressler
Journal: New England Journal of Medicine (1960)

THE success of present-day intensive antimicrobial therapy has altered the indications for pulmonary resection. Currently, surgical intervention is employed more often with the expectation of preventing relapse than for the immediate control of active disease in patients with pulmonary tuberculosis who were excreting drug-susceptible organisms before sputum conversion. At the thirty-eighth annual session of the American College of Physicians it was stated that "surgical intervention should be considered in all patients where there is a significant residual lesion, adequate potential life span and good pulmonary functions."1 To answer the question whether the residual lesion requires surgery, 100 sputum-negative patients with . . .
Class IA Phosphatidylinositol 3-Kinase in Pancreatic β Cells Controls Insulin Secretion by Multiple Mechanisms
Authors: Kazuma Kaneko, Kohjiro Ueki, Noriko Takahashi, Shinji Hashimoto, Masayuki Okamoto, Motoharu Awazawa, Yukiko Okazaki, Mitsuru Ohsugi, Kazunori Inabe, Toshihiro Umehara, Masashi Yoshida, Masafumi Kakei, Tadahiro Kitamura, Ji Luo, Rohit N. Kulkarni, C. Ronald Kahn, Haruo Kasai, Lewis C. Cantley, Takashi Kadowaki
Journal: Cell Metabolism (2010)
Acanthosis Nigricans Among Women With Gestational Diabetes Mellitus and Risk of Adverse Pregnancy Outcomes
Authors: Julie Daitchman, Marian J. Vermeulen, Joel G. Ray
Journal: Diabetes Care (2008)

Acanthosis nigricans (AN) is a cutaneous manifestation of insulin resistance (1). Among women with gestational diabetes mellitus (GDM), it is not known whether AN is associated with greater need for insulin therapy in pregnancy or adverse perinatal outcomes.

We performed a prospective cohort study of consecutive women with GDM or impaired glucose tolerance and a singleton pregnancy referred to the Diabetes in Pregnancy Clinic at St. Michael's Hospital in inner city Toronto. Patients received dietary counseling and began blood glucose testing four times a day. At the initial clinic visit, each woman was examined for AN of …
Mouth care and skin care in palliative medicine
Authors: C. Regnard, S. Allport, L. Stephenson
Journal: BMJ (1998)

EDITOR—We advocated a pragmatic approach to mouth and skin care in the ABC of Palliative Care.1 Not all the suggestions in the subsequent correspondence followed the same principle.2

Lucas and Roberts rightly point to the evidence for chlorhexidine in reducing oral bacteria. They fail to point out that chlorhexidine alters taste and can damage oral mucosa and that some randomised trials have shown it to be no better than water in preventing mucositis caused by treatments …