tbuckley/cabot-search huggingface dataset:
Case of Traumatic Gangrene: Successfully treated by the Local Application of Acetic Acid
Authors: J. W. West
Journal: BMJ (1842)

Members of the En and Wnt gene families seem to play a key role in the early specification of the brain territory that gives rise to the cerebellum, the midhindbrain junction. To analyze the possible continuous role of the En and Wnt signaling pathway in later cerebellar patterning and function, we expressed En-2 ectopically in Purkinje cells during late embryonic and postnatal cerebellar development. As a result of this expression, the cerebellum is greatly reduced in size, and Purkinje cell numbers throughout the cerebellum are reduced by more than one-third relative to normal animals. Detailed analysis of both adult and developing cerebella reveals a pattern of selectivity to the loss of Purkinje cells and other cerebellar neurons. This is observed as a general loss of prominence of cerebellar fissures that is highlighted by a total loss of sublobular fissures. In contrast, mediolateral patterning is generally only subtly affected. That En-2 overexpression selectively affects Purkinje cells in the transition zone between lobules is evidenced by direct observation of selective Purkinje cell loss in certain fissures and by the observation that growth and migration of the external germinal layer (EGL) is selectively retarded in the deep fissures during early postnatal development. Thus, in addition to demonstrating the critical role of Purkinje cells in the generation and migration of granule cells, the heterogeneous distribution of cellular effects induced by ectopic En expression suggests a relatively late morphogenetic role for this and other segment polarity proteins, mainly oriented at lobule junctions.
The 'Baby Doe' Rule
Authors: David K. Stevenson
Journal: JAMA (1986)

ON APRIL 9, 1982, "Baby Doe" was born in Bloomington, Ind. The series of events that followed, culminating in the "Baby Doe" rule, and their effects have been chronicled previously<sup>1,2</sup>and are summarized in the Table. The final version of the Baby Doe rule,<sup>3</sup>which was published Jan 12, 1984, and became effective Feb 13, 1984, reflects the history of emphasis on infants with severe congenital defects. The exceptions specified in the April 15, 1985, Child Abuse and Neglect Prevention and Treatment Program final rule also reflect the history of emphasis on easily identifiable conditions with predictable disabilities.<sup>4</sup>They appear to be adequate for selecting appropriate treatment options for certain infants such as an anencephalic fetus, for whom all treatment would be expected to be futile, or the infant with Down's syndrome with only duodenal atresia, for whom surgical treatment would clearly be a benefit. However, the
PREDICTION OF 5-YEAR CLINICAL OUTCOMES USING THE SYNTAX SCORE IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION FROM THE SIROLIMUS-ELUTING STENT COMPARED WITH PACLITAXEL-ELUTING STENT FOR CORONARY REVASCULARIZATION (SIRTAX) TRIAL
Authors: Chrysafios Girasis, Scot Garg, Lorenz Räber, Giovanna Sarno, Marie-angèle Morel, Hector Garcia-Garcia, Patrick W. Serruys, Stephan Windecker
Journal: Journal of the American College of Cardiology (2010)
Abstract LB-234: Suppression of Bruton tyrosine kinase with X-022, a highly selective next-generation irreversible inhibitor
Authors: Mark J. Mulvihill, Xiangyang Chen, JP Shaw, Richard Liu, Haihong Ni, Lee Babiss, Louis Renzetti
Journal: Cancer Research (2014)

Abstract BTK is a member of the TEC family of kinases and is a critical component of B cell receptor (BCR) signaling, promoting B cell maturation, survival and proliferation. BCR signaling is requisite in all B cell-mediated malignancies where clinical trials with BTK inhibitors have proven efficacious. X-Rx utilized its drug discovery platform and knowhow to advance multiple novel series of BTK inhibitors. X-022 was then identified as a next generation, oral small molecule BTK inhibitor. X-022 irreversibly inhibits BTK with an IC50 of 2.3 nM. In primary human B cell and HWB assays, X-022 inhibited B cell activity with IC50 values of 49 and 93 nM, respectively. X-022 showed superior selectivity against a panel of 456 kinases, only inhibiting at &amp;gt;90% BTK at a concentration of 1000 nM. Oral bioavailability of &amp;gt;20% is observed in mice, rats and dogs. In a mouse PK/PD model, X-022 showed a dose dependent decrease in B cell activation measured over an 8 hour time interval with &amp;gt;98% inhibition observed at 10 mg/kg po. In an established model of collagen induced arthritis in mice, X-022 caused a dose dependent decrease in disease severity consistent with mechanism of action. No safety issues were identified in a pilot study in rodents at doses up to 300 mg/kg po. X-022 is a promising next generation irreversible oral BTK inhibitor for the treatment of B cell malignancies and chronic autoimmune diseases. In addition, the high degree of selectivity combined with favorable molecular properties make X-022 an excellent candidate for co-formulation with other targeted therapeutics. Citation Format: Mark J. Mulvihill, Xiangyang Chen, JP Shaw, Richard Liu, Haihong Ni, Lee Babiss, Louis Renzetti. Suppression of Bruton tyrosine kinase with X-022, a highly selective next-generation irreversible inhibitor. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-234. doi:10.1158/1538-7445.AM2014-LB-234
Maternal and Perinatal Morbidity-Reply
Authors: H. Robert Harrison
Journal: JAMA (1984)

<h3>In Reply.—</h3> The letter by Dr Goodlin raises some points that require clarification. The definition of prematurity that we used is obstetrically correct. While it does not specifically address the question of good<i>v</i>poor infant outcome (ie, very premature<i>v</i>almost term infants), it does by definition address the problem of premature labor in its broad sense. The sample in which prematurity as an outcome was investigated was the 606 women enrolled at 24 weeks' or less gestation. Stratification by gestational age of the 108 premature outcomes that resulted, an analysis that addresses Dr Goodlin's concern, resulted in such small numbers of premature outcome per cell as to make associations among the multiple predictors and this outcome extremely difficult to demonstrate. As stated in the article, pregnancy information was collected and individual factors investigated against outcomes by contingency table analysis. Only those factors found to be significant were included
RELATION OF LABORATORY AIDS TO THE PRACTICE OF MEDICINE AND SURGERY
Authors: LEWIS A. CONNER
Journal: JAMA (1923)

To one, like myself, whose clinical life has stretched over a period well beyond thirty years, there is the constant inclination to compare the practice of medicine as it exists today with that as it existed when he began his work. One of the infallible signs of advancing years is the tendency to meditate on the changes that have taken place within one's personal experience. And to the physician who now has reached that meditative period, surely one of the most impressive facts in the evolution of the practice of medicine, as he has seen it, must be the tremendous growth of the laboratory side of medicine and the vast importance which these laboratory and instrumental aids have come to play in diagnosis and treatment.  When, in the summer of 1890, I entered the New York Hospital as an intern, the routine analysis of the urine and an occasional hemoglobin
Who Lives, Who Dies
Authors: Alexander G. Truesdell
Journal: Annals of Internal Medicine (2011)

On Being a Doctor6 December 2011Who Lives, Who DiesAlexander G. Truesdell, MDAlexander G. Truesdell, MDFrom Warren Alpert Medical School of Brown University, Providence, RI 02903.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-155-11-201112060-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail For centuries, soldiers and physicians have pondered the apparent random nature of life and death in battle. Does fate alone dictate who lives and who dies? Step to the left, and you survive the mortar strike. Switch convoy vehicles, and the IED devours your friend instead of you. Are such events predetermined? Or do our choices decide these outcomes?Across several combat deployments that followed the events of September 11th, every time I went to work I knew with reasonable certainty that someone would not come home. And not just “someone,” but a patient who was also a colleague or ... Author, Article, and Disclosure InformationAffiliations: From Warren Alpert Medical School of Brown University, Providence, RI 02903.Corresponding Author: Alexander G. Truesdell, MD, Warren Alpert Medical School of Brown University, Division of Cardiology, 593 Eddy Street, Providence, RI 02903; e-mail, [email protected]org. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 6 December 2011Volume 155, Issue 11Page: 790-791KeywordsArmed forcesDecision makingEmotionsHealth careHealth care facilitiesHospitalsPatientsSafetyShouldersSurgeons ePublished: 6 December 2011 Issue Published: 6 December 2011 Copyright & PermissionsCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Many Indian HIV patients drop out of healthcare before they qualify for antiretrovirals, study finds
Authors: C. Travasso
Journal: BMJ (2013)

Researchers in India have suggested that people with HIV be entitled to free antiretroviral treatment earlier in the development of their illness, to avoid their dropping out of regular assessment and missing out on treatment when they need it.

About half of patients with a diagnosis of HIV who are initially found to have a CD4 count considered too high for free treatment are lost to follow -up over the next four and a half years. Consequently they never receive antiretrovirals when their CD4 count falls below 200 cells ×109/L, when they would qualify for it.

India has 2.4 million people infected with HIV, the third highest burden in the world. However, little is known about …
Propensity-Matched Comparison of Morbidity and Costs of Open and Robot-Assisted Radical Cystectomies: A Contemporary Population-Based Analysis in the United States
Authors: Jeffrey J Leow, Stephen W Reese, Wei Jiang, Stuart R Lipsitz, Joaquim Bellmunt, Quoc-Dien Trinh, Benjamin I Chung, Adam S Kibel, Steven L Chang
Journal: European Urology (2014)
CNS-targeted LIF Expression Improves Therapeutic Efficacy and Limits Autoimmune-mediated Demyelination in a Model of Multiple Sclerosis
Authors: Helena Slaets, Jerome JA Hendriks, Chris Van den Haute, Frea Coun, Veerle Baekelandt, Piet Stinissen, Niels Hellings
Journal: Molecular Therapy (2010)

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) with an inflammatory and a neurodegenerative component. The neuropoietic cytokine leukemia inhibitory factor (LIF) is expressed in MS lesions, but its effect on lesion development is far from understood. LIF is an interesting candidate for MS therapy, as it has neuroprotective properties and may also promote the survival of myelinating oligodendrocytes (OLGs). However, therapeutic administration of LIF is complicated by its limited ability to cross the blood-brain barrier and its pleiotropic actions outside the CNS. In this study, lentiviral vectors (LVs) were used to achieve stable expression and secretion of LIF in the CNS of adult mice. CNS-targeted expression of LIF significantly reduced demyelination in a murine model of MS. In addition, local expression of LIF ameliorated clinical symptoms with enhanced efficacy compared to systemic treatment with recombinant protein. These findings demonstrate that gene therapeutic administration of LIF is a promising approach to limit lesion burden and clinical symptoms in neuroinflammatory disease.
Drugs in the Institutionalized Elderly-Reply
Authors: Don Riesenberg
Journal: JAMA (1989)

<h3>In Reply.—</h3> As Dr Kushnir points out, there are two sides to the anticholinergic coin. However, in elderly persons, serious adverse effects of anticholinergic psychotropics usually outweigh any secondary benefits. Dr Owen may be suffering from the "myopia" of which he accuses me when he writes that "the problem is the patients." How can both overmedicating and not overmedicating increase patients' risks of falls? Dr Loebel's data on the high prevalence of behavioral disturbances in the nursing home population are interesting. Nonetheless, I stand by my assertion that we can do better when it comes to prescribing psychotropic drugs for institutionalized elderly persons. One way we can do better, as Dr Owen suggests, is to frequent nursing homes.
Recent Advances in CT and MR Imaging for Evaluation of Hepatocellular Carcinoma
Authors: Jeong Min Lee, Jeong-Hee Yoon, Ijin Joo, Hyun Sik Woo
Journal: Liver Cancer (2012)

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Accurate diagnosis and assessment of disease extent are crucial for proper management of patients with HCC. Imaging plays a crucial role in early detection, accurate staging, and the planning of management strategies. A variety of imaging modalities are currently used in evaluating patients with suspected HCC; these include ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), nuclear medicine, and angiography. Among these modalities, dynamic MRI and CT are regarded as the best imaging techniques available for the noninvasive diagnosis of HCC. Recent improvements in CT and MRI technology have made noninvasive and reliable diagnostic assessment of hepatocellular nodules possible in the cirrhotic liver, and biopsy is frequently not required prior to treatment. Until now, the major challenge for radiologists in imaging cirrhosis has been the characterization of small cirrhotic nodules smaller than 2 cm in diameter. Further technological advancement will undoubtedly have a major impact on liver tumor imaging. The increased speed of data acquisition in CT and MRI has allowed improvements in both spatial and temporal resolution, which have made possible a more precise evaluation of the hemodynamics of liver nodules. Furthermore, the development of new, tissue-specific contrast agents such as gadoxetic acid has improved HCC detection on MRI. In this review, we discuss the role of CT and MRI in the diagnosis and staging of HCC, recent technological advances, and the strengths and limitations of these imaging modalities.
Body Fluid and Electrolyte Composition in Cardiac Patients with Severe Heart Disease but without Peripheral Edema
Authors: A. V. CHOBANIAN, B. A. BURROWS, W. HOLLANDER
Journal: Circulation (1961)

A LTHOUGH excessive retention of sodium and water is a striking feature in frank congestive heart failure, little is known about the abnormalities in body fluid and electrolyte metabolism in cardiac patients with severe heart disease prior to the development of ob- vious peripheral edema.Previous studies in nonedematous cardiac patients have not re- vealed any impairment in the handling of oral or intravenous sodium loads prior to the ap- pearance of edema.2 3 Therefore, the present study was undertaken to determine whether any abnormality in body fluid and electrolyte metabolism might be present in such patients even though they might appear to handle so- dium loads normally.When it was found that these nonedematous cardiac patients had sig- nificant increases in exchangeable sodium and radiosulfate space, it was decided to attempt to correlate such changes in body fluids and electrolytes with cardiovascular and renal hemodynamic function.
Tory MP demands to know how government will recoup 10m in NHS "pay-offs"
Authors: G. Iacobucci
Journal: BMJ (2014)

The chairman of the parliamentary health select committee is to write to England’s health secretary, Jeremy Hunt, to ask him to explain how senior NHS managers were awarded six figure redundancy payments during the government’s reorganisation of the NHS, only to be re-employed in the health service soon after.

The intervention from the Conservative Stephen Dorrell came after the Times published a list of 36 senior NHS bosses who received a total of more than £10m (€12.2m; $16.5m) in redundancy payments, including one manager paid £370 000 despite never leaving the health service at all.1

A total of 161 health bodies …
Periarteritis Nodosa and Other Forms of Necrotizing Angiitis*
Authors: Pearl M. Zeek
Journal: New England Journal of Medicine (1953)

PATHOLOGIC conditions characterized by inflammation and fibrinoid necrosis have constituted a perplexing and controversial subject in the medical literature for many years. The tendency in recent decades to include all lesions of this morphology in the category "periarteritis nodosa" has caused much confusion. The term "necrotizing angiitis" has been suggested1 as a more appropriate name to use collectively for all vascular lesions that are characterized in their fully developed stage by inflammatory reaction and fibrinoid necrosis, since this term is noncommittal so far as etiology is concerned and is applicable to lesions in vessels of any size, both arterial and . . .
SITUATIONAL AND ATTITUDINAL INFLUENCES ON RORSCHACH RESPONSES
Authors: ABRAHAM S. LUCHINS
Journal: American Journal of Psychiatry (1947)

Many of the manuals on the Rorschach present data for "normal" subjects which explicitly or implicitly are given as normal reference points. These reference points differ somewhat from manual to manual. They differ a good deal from the Rorschach data obtained from two army populations examined by the writer and his colleagues. Linn(8) also found discrepancies between the responses made by his soldiers and "normals" based on civilian populations. His explanation of the cause of the discrepancies does not seem to suffice for our groups. An attempt to throw light on the nature of their responses led to a detailed study, in the case of some of our subjects, of each card. This involved readministration of all the plates and was followed by a discussion with the subjects of their reactions. Their comments during this discussion helped to explain why they initially responded to the Rorschach plates as they had. These comments showed that the responses had been influenced by the operation of specific attitudes toward the test and the tester, by previous experiences, and by the educational, occupational and cultural background. They suggest the importance (a) of knowing this background, (b) of knowing the subject's assumptions about and attitudes toward the test and the examiner, (c) of preparing the subject for the test so that he will face it with the proper mental set and without false assumptions, and (d) of segregating those individuals who do not react adequately to ambiguous perceptual objects but who might give richer responses to tonal, manipulatory or verbal materials. A partial explanation of the differences in the various normal reference points for the Rorschach examination may be that the populations on whom the norms were based differed in backgrounds and attitudes. Perhaps the discrepancies in the "normals" is one indication of the difficulties involved when the Rorschach test, which was designed and extensively used for the diagnosis of psychiatric disorders, is applied to normal individuals. That which is an excellent tool for categorizing individuals into various disease entities, may require reevaluation before it is used for normal individuals. What may be needed is a thorough study of normal subjects' protocols without the use of present clinical concepts, percentages and ratios. This may lead to reconsideration of the significance of various categories and ratios of responses when made by normal individuals, and to the discovery of more adequate methods of studying normal personalities.
Stone formation in genetic hypercalciuric rats
Authors: David A. Bushinsky, Marc D. Grynpas, Erica L. Nilsson, Yasushi Nakagawa, Fredric L. Coe
Journal: Kidney International (1995)

Our genetic hypercalciuric (GH) rats have been selected and inbred for 29 generations to maximize urine calcium (UCa) excretion compared to identical gender controls (Ctl). To determine the effect of the increased UCa on urinary supersaturation and stone formation, we pair fed 15 GH and 15 Ctl rats a standard 1.2% calcium diet for 18 weeks, measured urine supersaturation every two weeks, and examined the urinary tract of 1/3 of the rats for the presence of stones every six weeks. Any stones formed were studied by SEM, X-ray and electron diffraction and X-ray microanalysis. Over the entire study UCa was increased in the GH compared to Ctl, resulting in greater supersaturation with respect to calcium hydrogen phosphate (CaHPO4) at all times and calcium oxalate (CaOx) at most times. There was a progressive increase in the incidence of stone formation in GH rats with one of five rats having stones at six weeks, three of five with stones at 12 weeks and five of five with stones at 18 weeks. There were no stones formed in Ctl rats. SEM reveals discrete stones and not nephrocalcinosis. X-ray and electron diffraction and X-ray microanalysis reveal the stones to be poorly crystalline apatite which is a solid phase of calcium and phosphate. Compared to Ctl, in the GH rats the saturation ratio for CaHPO4 increased proportionally more than that for CaOx, perhaps explaining why the rats formed apatite and not oxalate stones. This is the first description of an animal model of spontaneous nephrolithiasis.
Consultant surgeon advised to stop operating
Authors: R. Dobson
Journal: BMJ (1997)

A consultant cardiac surgeon whose operative mortality was found to be significantly poorer than the average of his colleagues should not resume operating, a team of external assessors has advised.

James Wisheart, aged 58, voluntarily stopped operating last year, and he has since resigned as medical director of United Bristol Healthcare NHS Trust. He has also announced his decision to retire.

The external assessment of adult heart surgery at the …
IMMUNOLOGIC STUDIES OF THE MAJOR NONIMMUNOGLOBULIN PROTEIN OF AMYLOID
Authors: Mark Levin, Mordechai Pras, Edward C. Franklin
Journal: The Journal of Experimental Medicine (1973)

Antisera have been prepared against the major nonimmunoglobulin component of secondary and familial Mediterranean fever (FMF) associated amyloid which has been called A component or acid soluble fraction (ASF). The antisera were shown to be monospecific for ASF by precipitation of (125)I-labeled antigen and gave a reaction of identity with four different ASF preparations. The antisera were able to detect a circulating component in human serum that migrated in the alpha1-globulin region. This circulating component gave a line of identity with degraded ASF by double immunodiffusion. 57 normal sera and 89 sera from patients with diseases known to be frequently associated with amyloidosis were tested by immunodiffusion for the circulating ASF component. 7% of normal sera and 50-80% of the pathologic sera had elevated amounts of this component. Absorption studies showed that all normal sera probably have small amounts of this component while cord sera do not have detectable amounts. This component was partially purified and was shown to be slightly larger than albumin. The relation of the circulating component to the acid soluble fraction of amyloid is discussed.
Aspects of management
Authors: A. L. Hepburn, T. G. Rider, K. M. Jordan
Journal: BMJ (2011)

In response to Cayley’s article,1 we would like to clarify some important aspects of the management of gout. In acute gout, we would recommend 0.5 mg of colchicine two to three times daily for three days, in accordance with published guidelines.2 More frequent (one to two hourly) dosing should be avoided, …