tbuckley/cabot-search huggingface dataset:
Dermatologic Conditions Misdiagnosed as Evidence of Child Abuse-Reply
Authors: Marcia E. Herman-Giddens
Journal: JAMA (1989)

<h3>In Reply.—</h3> Lichen sclerosus et atrophicus is one of a number of diagnoses that can be mistaken for evidence of sexual abuse. We appreciate the comments of Drs Anders, Smith, and Koblenzer in providing the opportunity to discuss this condition. As the authors point out, misdiagnosis in child abuse may have even more serious ramifications than in many other areas of pediatrics. It is paramount that professionals who specialize in child abuse be familiar with differential diagnoses that include other conditions that might present as apparent physical or sexual abuse. Indeed, one must be familiar with endocrinologic and metabolic disorders, inflammatory bowel diseases, and infectious diseases as well as the field of dermatology. We, too, have seen several patients with lichen sclerosus et atrophicus who have been mistakenly diagnosed and referred to us because it was believed that the children were being abused sexually. Recently, we evaluated a 6-year-old girl
Medical Marijuana and the Law
Authors: Diane E. Hoffmann, Ellen Weber
Journal: New England Journal of Medicine (2010)

The U.S. legal landscape surrounding "medical marijuana" is complex and rapidly changing. Fourteen states — California, Alaska, Oregon, Washington, Maine, Hawaii, Colorado, Nevada, Vermont, Montana, Rhode Island, New Mexico, Michigan, and most recently, New Jersey — have passed laws eliminating criminal penalties for using marijuana for medical purposes, and at least a dozen others are considering such legislation.1 Medical experts have also taken a fresh look at the evidence regarding the therapeutic use of marijuana,2,3 and the American Medical Association (AMA) recently adopted a resolution urging review of marijuana as a Schedule I controlled substance, noting it would support . . .
SLOWED VENTRICULAR UNTWISTING IS RELATED TO DECREASED ELASTIC RECOIL BUT NOT TO INCREASED MYOCARDIAL FIBROSIS IN HYPERTROPHIC CARDIOMYOPATHY
Authors: Ayumi Nakaboh, Akiko Goda, Katsumi Oka, Misato Otsuka, Mika Matsumoto, Chikako Yoshida, Akiyo Eguchi, Shohei Fujiwara, Naoki Yoshimoto, Masaaki Lee-Kawabata, Takeshi Tsujino, Tohru Masuyama
Journal: Journal of the American College of Cardiology (2010)
Management of acute symptomatic hyponatraemia
Authors: C Heneghan, P Goldrick, H Pham
Journal: BMJ (1994)

Another study found that the response rate to a questionnaire was significantly higher when the covering letter was written by the patient's general practitioner than when it was written by a doctor in a research unit.3It seems sensible to devote attention to the covering letter, making it personal and attractive and stating the purposes and sponsorship of the
Coronary Artery Spatial Distribution of Acute Myocardial Infarction Occlusions
Authors: John C. Wang, Sharon-Lise T. Normand, Laura Mauri, Richard E. Kuntz
Journal: Circulation (2004)

Acute coronary occlusions leading to ST-segment elevation myocardial infarctions (STEMIs) are due primarily to rupture of atherosclerotic plaques. Present "vulnerable plaque" detection technology focuses on identifying individual plaques with no clear therapeutic plan beyond conventional risk factor reduction. We developed a spatial map of the distribution of acute coronary occlusions to test our hypothesis that plaque ruptures do not occur uniformly throughout the coronary tree.We analyzed 208 consecutive patients who presented to the Brigham and Women's Hospital with STEMI and mapped the location of the acute coronary occlusion. These occlusions were not uniformly distributed throughout each of the major epicardial coronary arteries but tended to cluster within the proximal third of each of the vessels (right coronary artery, P=0.001; left anterior descending artery, P=0.003; left circumflex artery, P=0.001). Furthermore, Poisson regression showed that for each 10-mm increase in distance from the ostium, the risk of an acute coronary occlusion was significantly decreased by 13% in the right coronary artery, 30% in the left anterior descending artery, and 26% in the left circumflex artery.Acute coronary occlusions leading to STEMI tend to cluster in predictable "hot spots" within the proximal third of the coronary arteries. Identification of these high-risk zones for acute coronary occlusions will lead to future advances in vulnerable plaque detection technology and potentially locally directed preventive strategies.
Nephrology beyond JASN
Authors: SD Crowley, SB Gurley, MI Oliverio, AK Pazmino, R Griffiths, PJ Flannery, RF Spurney, H-S Kim, O Smithies, TH Le, TM Coffman
Journal: Journal of the American Society of Nephrology (2005)

In the past wise rabbis had stated: “The human body was given ten organs of which it is the task of the kidney to provide the human body with thought” (Talmud Brochot). This view of the kidney, although immensely flattering to nephrologists, is no longer universally accepted today. A remaining
Arousal in patients with gastro-oesophageal reflux and sleep apnoea
Authors: T Penzel, HF Becker, U Brandenburg, T Labunski, W Pankow, JH Peter
Journal: European Respiratory Journal (1999)

Nocturnal gastro-oesophageal reflux has been observed in patients with obstructive sleep apnoea (OSA). Negative intrathoracic pressure during apnoeas and arousal have been suggested as the underlying mechanisms. In order to evaluate this hypothesis, the coincidence and sequence in time of arousal, apnoea and reflux events were analysed. Fifteen patients with OSA or heavy snoring were studied by means of standard polysomnograpy with parallel recording of 24-h oesophageal pH. Reflux events during the day were present in all patients, five of whom had symptoms of reflux. In three of these and in five other patients, a total of 69 nocturnal reflux events were found. In 68 events, arousal was found with the reflux event. Only one reflux without arousal was found (sleep stage 2). Seventeen events occurred during wakefulness after sleep onset. The percentage of time with a pH of &lt;4 during wakefulness after sleep onset was significantly higher than the percentage of time with a pH of &lt;4 during total sleep time (p&lt;0.05). In 37 of the 52 reflux events which occurred during sleep, either an apnoea or a hypopnoea was found prior to the event. The investigation of sequence in time did not prove a causal relation between respiratory events and reflux events. The results indicate that gastro-oesophageal reflux and obstructive sleep apnoea are two separate disorders, which both have a high prevalence in obese patients.
Abstract 5238: Acquired therapeutic resistance is mediated by deregulation of multiple pathways.
Authors: Laura M. Heiser, Chad A. Shaw, Nicholas J. Wang, Catie Grasso, Pavana Anur, Sam Ng, Theodore Goldstein, Paul T. Spellman, Joshua Stuart, Kent Osborne, Joe Gray, Rachel Schiff
Journal: Cancer Research (2013)

Abstract The HER2-directed antibody, trastuzumab combined with chemotherapy, has markedly improved outcome of patients with HER2-amplified breast cancer, yet both de novo and acquired resistance occur in a substantial subset of patients. To study the molecular underpinnings of acquired resistance, we have developed a panel of 30 unique HER2+ cell lines that have been cultured to become resistant to lapatinib, trastuzumab and the combination treatment. Each of these models underwent next-generation sequencing to elucidate mechanisms of resistance to HER2 therapies. We hypothesized that resistance may be mediated by modulation of particular pathways - rather than by individual genes. With this idea in mind, we performed a PARADIGM pathway analysis that integrates information from multiple genomic data types to calculate pathway activity scores. The PARADIGM SuperPathways represent 1321 cell signaling pathways curated from sources such as KEGG, BioCarta, and Reactome. We populated the networks with the copy number (ExomeSeq) and expression (RNAseq) datasets that had been normalized to identify contrasts between parental and resistant lines. For each pathway, we computed a Pathway Activity Score as the sum of the absolute value of each node in the pathway, normalized by the total number of pathway nodes. Nearly 30% of the curated pathways (361/1321) are strongly deregulated in at least one of the network models, whereas a much smaller subset (3%) were strongly deregulated across multiple resistance cell line models. Frequently deregulated pathways include hemoglobin chaperone, ATM mediated phosphorylation of repair proteins, the HIF2alpha transcription factor network and the PLK signaling events in the cell cycle. All together, these findings indicate that resistance is mediated through many signaling mechanisms. Furthermore, the acquired resistance-related aberrations suggest possible second-line treatment strategies that may be effective. Citation Format: Laura M. Heiser, Chad A. Shaw, Nicholas J. Wang, Catie Grasso, Pavana Anur, Sam Ng, Theodore Goldstein, Paul T. Spellman, Joshua Stuart, Kent Osborne, Joe Gray, Rachel Schiff. Acquired therapeutic resistance is mediated by deregulation of multiple pathways. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5238. doi:10.1158/1538-7445.AM2013-5238
Goiter in Gandhara-Reply
Authors: Baruch S. Blumberg
Journal: JAMA (1965)

1. It was very interesting to hear from a physician currently practicing in an area near Gandhara. It is difficult to compromise Dr. Frewing's findings on goiter frequency with those recorded by the investigators cited in the communication. It is conceivable that there has been some change in the frequency in these areas described by Dr. Frewing since the original studies. Another explanation is that the frequency may be lower in those individuals who present themselves for employment; those with very large goiters or with symptoms may not be as frequently represented in the labor pool as in the general population. Goiter is generally more common in females than males and most of the subjects seen by Dr. Frewing were males. In reference to the dependent female group seen by Dr. Frewing, they may also have a lower frequency than females in the general population, since goiter is thought to be familial. As noted above, the
CD151 modulates expression of matrix metalloproteinase 9 and promotes neoangiogenesis and progression of hepatocellular carcinoma
Authors: Guo-Ming Shi, Ai-Wu Ke, Jian Zhou, Xiao-Ying Wang, Yang Xu, Zhen-Bin Ding, Ranjan Prasad Devbhandari, Xiao-Yong Huang, Shuang-Jian Qiu, Ying-Hong Shi, Zhi Dai, Xin-Rong Yang, Guo-Huan Yang, Jia Fan
Journal: Hepatology (2010)

Tetraspanin CD151 is involved in several pathological activities associated with tumor progression, including neoangiogenesis. However, the role and molecular mechanism of CD151 in the neoangiogenesis of hepatocellular carcinoma (HCC) remain enigmatic. We found that the level of expression of matrix metalloproteinase 9 (MMP9) was positively associated with CD151 expression in HCC cells. We developed a zone-by-zone blockade and demonstrated that overexpression of CD151 in HCC cells facilitated MMP9 expression through a phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase 3β (GSK-3β)/Snail signaling pathway. In contrast, down-regulation of CD151 expression impaired the ability of HCC cells to form microvessels in vitro and reduced their in vivo metastatic potential. In a clinical setting, a significant correlation of the expression of CD151 with MMP9 expression and with microvessel density (MVD) was revealed by Pearson correlation analysis of HCC patients. The postoperative 3-, 5-, and 7-year overall survival rates of HCC patients with CD151high/MMP9high/MVDhigh were significantly lower than those of the CD151low/MMP9low/MVDlow group or groups in which only one or two of CD151, MMP9, and MVD were highly expressed. Cumulative recurrence rates were also highest in HCC patients with CD151high/MMP9high/MVDhigh in comparison with the other groups. Multivariate Cox proportional hazards analysis showed that the concomitant overexpression of CD151, MMP9, and MVD was an independent marker for predicting poor prognosis of HCC. Conclusion: Overexpression of CD151 up-regulated the expression of MMP9 through the PI3K/Akt/GSK-3β/Snail pathway. CD151-dependent neoangiogenesis appeared to promote the progression of HCC, and this suggests that CD151 may be useful as a high-priority therapeutic target for antiangiogenesis in HCC. Hepatology 2010
Selective decontamination of the digestive tract and selective oropharyngeal decontamination reduced mortality in the ICU
Authors: Daniel D. Dressler, Amir K. Jaffer
Journal: Annals of Internal Medicine (2009)

ACP Journal Club19 May 2009Selective decontamination of the digestive tract and selective oropharyngeal decontamination reduced mortality in the ICUDaniel D. Dressler, MD, MSc, Amir K. Jaffer, MDDaniel D. Dressler, MD, MScEmory University, Atlanta, Georgia, USA (D.D.D.)Search for more papers by this author, Amir K. Jaffer, MDUniversity of Miami Miller School of Medicine, Miami, Florida, USA (A.K.J.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-150-10-200905190-02005 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source Citationde Smet AM, Kluytmans JA, Cooper BS, et al. Decontamination of the digestive tract and oropharynx in ICU patients. N Engl J Med. 2009;360:20-31. https://pubmed.ncbi.nlm.nih.gov/19118302Clinical Impact RatingsHospitalists: Infectious Disease: Critical Care: Pulmonology: References1 D’Amico R, Pifferi S, Leonetti C, et al. Effectiveness of antibiotic prophylaxis in critically ill adult patients: systematic review of randomised controlled trials. BMJ. 1998;316:1275-85. [PMID: 9554897] Google Scholar2 Nathens AB, Marshall JC. Selective decontamination of the digestive tract in surgical patients: a systematic review of the evidence. Arch Surg. 1999;134:170-6. [PMID: 10025458] Google Scholar3 Chan EY, Ruest A, Meade MO, Cook DJ. Oral decontamination for prevention of pneumonia in mechanically ventilated adults: systematic review and meta-analysis. BMJ. 2007;334:889. [PMID: 17387118] Google Scholar Author, Article, and Disclosure InformationAffiliations: Emory University, Atlanta, Georgia, USA (D.D.D.)University of Miami Miller School of Medicine, Miami, Florida, USA (A.K.J.)This article was published at Annals.org on 5 May 2009. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByPro descontaminación selectiva 19 May 2009Volume 150, Issue 10Page: JC5-5KeywordsAntibioticsDecontaminationGastrointestinal tractIntensive care unitsOropharynxStomachSystematic reviewsVentilators ePublished: 19 May 2009 Issue Published: 19 May 2009 CopyrightCopyright © 2009 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Abstract 2965: <i>Dissecting the molecular mechanism of TLX1-mediated T-cell acute lymphoblastic leukemia development using an in vitro immortalization model</i>
Authors: Lynnsey A. Zweier-Renn, Teresa S. Hawley, Ali Ramezani, Irene Riz, Robert G. Hawley
Journal: Cancer Research (2010)

Abstract Inappropriate activation of the TLX1 homeobox gene (previously known as HOX11) by chromosomal translocation is a recurrent event in human T-cell acute lymphoblastic leukemia (T-ALL). Enforced expression of TLX1 in murine hematopoietic stem/progenitor cells using a conventional retroviral vector yields immortalized hematopoietic progenitor cell lines. Recent clinical gene therapy trials have shown that retroviral vectors can cause insertional activation of proto-oncogenes which has resulted in the development of hematopoietic clonal dominance or T-ALL-like diseases. Our lab has developed an insulated self-inactivating retroviral vector, RMSinOFB, which has been safety-modified to virtually eliminate insertional genotoxicity during transgene delivery. To observe the effect of reducing retroviral genotoxicity during TLX1 gene transfer, we subcloned the TLX1 gene into the RMSinOFB vector for ectopic expression in murine hematopoietic stem/progenitor cells. Post transduction, TLX1-expressing bone marrow cells had a growth/survival advantage, and readily gave rise to immortalized cell lines. To determine whether insertional mutagenesis played a role in TLX1-mediated immortalization, we identified the integration sites in 15 TLX1-immortalized hematopoietic cell lines by LM-PCR. No common immortalizing genes, such as Evi1 or Prdm16, were identified among the cell lines which underlines the importance of TLX1 transcriptional properties for cell immortalization. Additionally, when tested by RT-PCR no differential vector-influenced expression was observed for candidate genes nearest the integration sites compared to the cell lines lacking such insertions. Furthermore, gene ontology analysis of genes within 100-kb windows of the integration sites did not reveal overrepresentation of a particular functional group. Although several laboratories recently reported the generation of hematopoietic progenitor cell lines due to insertional mutagenesis by retroviral vector backbones, these results confirm and extend our previous findings suggesting that constitutive TLX1 expression alone is sufficient to initiate the series of events culminating in hematopoietic progenitor cell immortalization. We are currently investigating whether non insertion site-related mutations, such as inactivation of the Cdkn2a tumor suppressor locus which collaborates with TLX1 during human T-cell leukemogenesis, may contribute to the process. Investigating the molecular mechanism of TLX1-mediated cellular immortalization in our in vitro model should provide a better understanding of the early stages of TLX1-associated T-ALL development. 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 2965.
THE OCCURRENCE OF OPTIC NERVE ATROPHY IN GENERAL DISEASE.
Authors: H. V. WÜRDEMANN
Journal: JAMA (1896)

The origin of most cases of optic nerve atrophy is certainly obscure. There can be no doubt, when the amblyopia and characteristic disk changes follow traumatism, peripheral disease, or there is positive diagnosis of cerebral disease, or following the continued action of some virus or poison in the system, that is known to affect the optic nerve. The occurrence of optic nerve atrophy in general disease always brings with it doubt as to the causative relation. The statements of patients are unreliable especially as regards nature, duration and severity of preëxisting diseases and an element of doubt is always attached to the relation of such a chronic process as nerve atrophy which may have begun months or years after an apparently well authenticated cause. The atrophy may involve the whole structure of the optic nerve for its whole length, or may be complete in only a portion; it may effect
Making Medicines Safer — The Need for an Independent Drug Safety Board
Authors: Alastair J.J. Wood, C. Michael Stein, Raymond Woosley
Journal: New England Journal of Medicine (1998)

Dexfenfluramine (Redux) was withdrawn from the market in the United States in 1997 amid speculation that millions who used it could have been harmed.13 More recently, mibefradil (Posicor) was withdrawn because of suggestions that it may have serious interactions with other drugs.4 Adverse reactions to drugs are an important cause of morbidity and mortality; it has been estimated recently that approximately 100,000 Americans die every year as a result of such adverse reactions,5 making them one of the most common causes of death. Independent agencies exist to investigate airline accidents, railroad mishaps, and radiation spills and to make recommendations . . .
Associations between α-Tocopherol, β-Carotene, and Retinol and Prostate Cancer Survival
Authors: Joanne L. Watters, Mitchell H. Gail, Stephanie J. Weinstein, Jarmo Virtamo, Demetrius Albanes
Journal: Cancer Research (2009)

Previous studies suggest that carotenoids and tocopherols (vitamin E compounds) may be inversely associated with prostate cancer risk, yet little is known about how they affect prostate cancer progression and survival. We investigated whether serum alpha-tocopherol, beta-carotene, and retinol concentrations, or the alpha-tocopherol and beta-carotene trial supplementation, affected survival of men diagnosed with prostate cancer during the alpha-Tocopherol, beta-Carotene Cancer Prevention Study, a randomized, double-blind, placebo-controlled primary prevention trial testing the effects of beta-carotene and alpha-tocopherol supplements on cancer incidence in adult male smokers in southwestern Finland (n = 29,133). Prostate cancer survival was examined using the Kaplan-Meier method with deaths from other causes treated as censoring, and using Cox proportional hazards regression models with hazard ratios (HR) and 95% confidence intervals (CI) adjusted for family history of prostate cancer, age at randomization, benign prostatic hyperplasia, age and stage at diagnosis, height, body mass index, and serum cholesterol. As of April 2005, 1,891 men were diagnosed with prostate cancer and 395 died of their disease. Higher serum alpha-tocopherol at baseline was associated with improved prostate cancer survival (HR, 0.67; 95% CI, 0.45-1.00), especially among cases who had received the alpha-tocopherol intervention of the trial and who were in the highest quintile of alpha-tocopherol at baseline (HR, 0.51; 95% CI, 0.20-0.90) or at the 3-year follow-up measurement (HR, 0.26; 95% CI, 0.09-0.71). Serum beta-carotene, serum retinol, and supplemental beta-carotene had no apparent effects on survival. These findings suggest that higher alpha-tocopherol (and not beta-carotene or retinol) status increases overall prostate cancer survival. Further investigations, possibly including randomized studies, are needed to confirm this observation.
Variability in the size of individual airways over the course of one year.
Authors: R H Brown, E A Zerhouni, W Mitzner
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Several studies have examined the reproducibility over time of standard clinical measurements of pulmonary airways parameters, such as FEV1 and FVC. These studies indicate fairly consistent reproducibility of such measurements over periods of months and years. Although such traditional pulmonary function tests can provide quantitative measures of lung function, they do not provide any insight into the local or regional variation of individual airways. Therefore, in a longitudinal study in dogs, we directly measured the baseline size (cross-sectional area) of the same individual canine airways multiple times over a 1-yr period, using high-resolution computed tomography (HRCT). We compared the variability of individual airway size both within and between subjects to the various sizes of airways and to seasonal differences in size. Five anesthetized, intubated, and ventilated dogs were studied between five and eight times over a 15-mo period. HRCT scans were acquired at end expiration with the dogs at FRC on all occasions. All individual airways showed considerable variability in size over time as measured by the coefficient of variation (CV) (range: 9.2 to 69.3). The sizes of individual airways within a dog were seen to change by as much as twofold over time. Some dogs also showed significantly greater overall variability in airway size than did other dogs (p < 0.01), but this variability was related neither to the size of the airway (p = 0.34) nor to the season. These findings indicate a substantial local and regional variability in airway caliber that would not be detectable with conventional pulmonary function tests.(ABSTRACT TRUNCATED AT 250 WORDS)