tbuckley/cabot-search huggingface dataset:
Chromosomal Alterations in Ductal Carcinomas In Situ and Their In Situ Recurrences
Authors: F. M. Waldman
Journal: JNCI Journal of the National Cancer Institute (2000)

Ductal carcinoma in situ (DCIS) recurs in the same breast following breast-conserving surgery in 5%-25% of patients, with the rate influenced by the presence or absence of involved surgical margins, tumor size and nuclear grade, and whether or not radiation therapy was performed. A recurrent lesion arising soon after excision of an initial DCIS may reflect residual disease, whereas in situ tumors arising after longer periods are sometimes considered to be second independent events. The purpose of this study was to determine the clonal relationship between initial DCIS lesions and their recurrences.Comparative genomic hybridization (CGH) was used to compare chromosomal alterations in 18 initial DCIS lesions (presenting in the absence of invasive disease) and in their subsequent ipsilateral DCIS recurrences (detected from 16 months to 9.3 years later).Of the 18 tumor pairs, 17 showed a high concordance in their chromosomal alterations (median = 81%; range = 65%-100%), while one case showed no agreement between the paired samples (having two and 20 alterations, respectively). Morphologic characterization of the DCIS pairs showed clear similarities. The mean number of CGH changes was greater in the recurrent tumors than in the initial lesions (10.7 versus 8.8; P =.019). The most common changes in both the initial and the recurrent in situ lesions were gains involving chromosome 17q and losses involving chromosomes 8p and 17p. The degree of concordance was independent of the time interval before recurrence and of the presence of positive surgical margins.In this study, DCIS recurrences were clonally related to their primary lesions in most cases. This finding is consistent with treatment paradigms requiring wide surgical margins and/or postoperative radiation therapy.
Life Is Short, the Art Long, Opportunity Fleeting, Experience Treacherous, Judgment Difficult-Reply
Authors: Lloyd M. Krieger
Journal: JAMA (1988)

In Reply.  — Dr Conner makes some fine points in his letter but he is wrong to imply that I did not receive a comprehensive physical examination. Indeed, many physicians gave me thorough abdominal and rectal examinations; at no time did I have signs of acute appendicitis. Overall, the care I received was superb. Hence the dilemma: Why did the best medical minds and technology miss a relatively simple ruptured appendix?  Immediately after my hospitalization, I was disillusioned with medicine. I learned—the hard way—that no diagnosis is uniformly simple. But hindsight is always 20/20, and it is easy in retrospect to say that the diagnosis should have been obvious. It is not difficult to explain why a given team won the Superbowl after the game is over.  Medicine is an art and a science. Its proper execution depends on the interaction of the physician and technology. Physicians are not magicians,
Atrial L-Type Ca <sup>2+</sup> Currents and Human Atrial Fibrillation
Authors: David R. Van Wagoner, Amber L. Pond, Michelle Lamorgese, Sandra S. Rossie, Patrick M. McCarthy, Jeanne M. Nerbonne
Journal: Circulation Research (1999)

Abstract —Chronic atrial fibrillation (AF) is characterized by decreased atrial contractility, shortened action potential duration, and decreased accommodation of action potential duration to changes in activation rate. Studies on experimental animal models of AF implicate a reduction in L-type Ca 2+ current ( I Ca ) density in these changes. To evaluate the effect of AF on human I Ca , we compared I Ca in atrial myocytes isolated from 42 patients in normal sinus rhythm at the time of cardiac surgery with that of 11 chronic AF patients. I Ca was significantly reduced in the myocytes of patients with chronic AF (mean −3.35±0.5 pA/pF versus −9.13±1.0 pA/pF in the controls), with no difference between groups in the voltage dependence of activation or steady-state inactivation. Although I Ca was lower in myocytes from the chronic AF patients, their response to maximal β-adrenergic stimulation was not impaired. Postoperative AF frequently follows cardiac surgery. Half of the patients in the control group (19/38) of this study experienced postoperative AF. Whereas chronic AF is characterized by reduced atrial I Ca , the patients with the greatest I Ca had an increased incidence of postoperative AF, independent of patient age or diagnosis. This observation is consistent with the concept that calcium overload may be an important factor in the initiation of AF. The reduction in functional I Ca density in myocytes from the atria of chronic AF patients may thus be an adaptive response to the arrhythmia-induced calcium overload.
A Phase 1B Study of Brivanib in Combination with 5FU/LV and FOLFIRI in Patients with Advanced or Metastatic Gastro-Intestinal Malignancies
Authors: A. Hollebecque, A. El-Khoueiry, D.J. Jonker, M.B. Sawyer, L. Wong, C.R. Becerra, J.C. Soria, J.M. Chemidlin, G. Kollia, D.S.A. Nuyten
Journal: Annals of Oncology (2013)
Use of Health Care Services by Lower-Income and Higher-Income Uninsured Adults
Authors: Joseph S. Ross, Elizabeth H. Bradley, Susan H. Busch
Journal: JAMA (2006)

More than 45 million individuals in the United States lack health insurance, potentially limiting their access to and use of appropriate health care services. Although the uninsured comprise a range of income levels, little attention has been directed at higher-income uninsured adults and their patterns of care.To examine whether having higher income attenuates the association between being uninsured and using fewer recommended health care services.Cross-sectional analysis of data from the 2002 Behavioral Risk Factor Surveillance System, drawn from a nationally representative sample of households. Participants were community-dwelling adults (n = 194 943; 50% women) aged 18 to 64 years in 2002.Self-reported use of screening for cervical, breast, and colorectal cancer; serum cholesterol screening and measurement, aspirin use, and tobacco cessation and weight loss counseling for cardiovascular risk reduction; and serum cholesterol and glycosylated hemoglobin measurement, eye and foot examination, and influenza and pneumococcal vaccination for diabetes management.Among eligible adults, use of cancer prevention services ranged from 51% for colorectal cancer screening to 88% for cervical cancer screening, while use of cardiovascular risk reduction services ranged from 38% for weight loss counseling to 81% for aspirin use, and use of services for diabetes management ranged from 33% for pneumococcal vaccination to 88% for serum glycosylated hemoglobin measurement. In bivariate analyses, health insurance and annual household income were both strongly associated with use of nearly all examined health care services (P values <.01). Using multivariable analysis, increased annual household income did not significantly increase the likelihood of uninsured compared with insured adults receiving recommended health care services for cancer prevention, cardiovascular risk reduction, or diabetes management (P values >.05).Even among higher-income adults, lack of health care insurance was associated with significantly decreased use of recommended health care services; increased income did not attenuate the difference in use between uninsured and insured adults. Efforts to improve the use of recommended health care services among the uninsured should focus on patient education and expanding insurance eligibility for both lower-income and higher-income adults.
Rheumatoid lung disease, pneumothorax, and eosinophilia.
Authors: A J Crisp, R D Armstrong, R Grahame, J E Dussek
Journal: Annals of the Rheumatic Diseases (1982)

Four cases of the triad of rheumatoid lung disease, spontaneous pneumothorax, and peripheral blood eosinophilia are reported. Cavitation of a rheumatoid lung nodule caused the pneumothorax in at least 1 case. The significance of eosinophilia and its value as a marker of extra-articular manifestations of rheumatoid disease are discussed.
Promyelocytic Leukemia Protein (Pml) and Daxx Participate in a Novel Nuclear Pathway for Apoptosis
Authors: Sue Zhong, Paolo Salomoni, Simona Ronchetti, Ailan Guo, Davide Ruggero, Pier Paolo Pandolfi
Journal: The Journal of Experimental Medicine (2000)

The promyelocytic leukemia protein (PML) gene of acute promyelocytic leukemia (APL) encodes a cell growth and tumor suppressor essential for multiple apoptotic signals. Daxx was identified as a molecule important for the cytoplasmic transduction of the Fas proapoptotic stimulus. Here, we show that upon mitogenic activation of mature splenic lymphocytes, Daxx is dramatically upregulated and accumulates in the PML nuclear body (NB) where PML and Daxx physically interact. In the absence of PML, Daxx acquires a dispersed nuclear pattern, and activation-induced cell death of splenocytes is profoundly impaired. PML inactivation results in the complete abrogation of the Daxx proapoptotic ability. In APL cells, Daxx is delocalized from the NB. Upon retinoic acid treatment, which induces disease remission in APL, Daxx relocalizes to the PML NBs. These results indicate that PML and Daxx cooperate in a novel NB-dependent pathway for apoptosis and shed new light in the role of PML in tumor suppression.
Drugs and the Athlete
Authors: James E. Wright
Journal: JAMA (1990)

<i>Drugs and the Athlete</i>is an exceptionally well-researched book, written by an eminently qualified internist-neurologist team with backgrounds both in competitive athletics and in treatment of substance abuse. This is a unique combining in a single, coherent source, and it is so well written that individuals with little specialized training will easily be able to understand the knowledge and techniques presented. The subject is important. Drugs are taking an enormous toll on society, the full impact of which is yet to be felt. Abuse of drugs, particularly addictive ones, undermines all traditional values and even instinctive self-preservation behavior. Wholesale drug abuse has now invaded the previously purist realm of athletics. Athletes of both sexes, at all levels, and in virtually every sport abuse all the drugs nonathletes do and many that they don't. As incredible as it may seem, participation in athletics has itself apparently become a significant risk factor
Hospitals have more negotiating power than commissioning groups, Monitor says
Authors: G. Iacobucci
Journal: BMJ (2013)

Poor quality data and weak contracting skills are undermining the effective commissioning of healthcare services in England, new research from the regulator Monitor has found.

The study1 found that healthcare providers hold too much negotiating power, with commissioners sometimes lacking strong contracting skills, and are often unwilling to impose financial sanctions on providers.

The paper, “Local price setting and contracting practices for NHS services without a nationally mandated price”, has been published ahead of Monitor …
Nuclear Threat: What About the Russians?-Reply
Authors: Christine K. Cassel
Journal: JAMA (1985)

In Reply.—  Drs Van Coevering and Deusenberg have raised similar aspects of the same point, which has its generic form in the question, What about the Russians? This question is responsible for a lack of clear reasoning about nuclear weapons policy among certain government officials as well as among the general public. No matter how atrocious the totalitarian state of the USSR may be (and I agree that it is) and no matter how objectionable the notion of Communist morality may be (and I agree that it is), a frantic buildup of yet more nuclear weapons will not protect us from any threat posed by the Soviet Union nor will it change the nature of that country's government. By increasing reliance on nuclear rather than conventional arms, we lower the threshold for beginning a nuclear war. If these weapons are used, it is clear that both sides lose, and life
PYELOVENOUS BACK FLOW
Authors: CLARENCE E. BIRD
Journal: JAMA (1926)

A reflux of material from the renal pelvis into the veins of the kidney was described in a recent communication by Hinman and Lee-Brown.<sup>1</sup>The reflux occurred at low intrapelvic pressures varying from 30 to 60 mm. of mercury both in the living and in the recently removed kidneys of sheep, rabbits and dogs. Although the site of this "pyelovenous back flow" was not definitely determined, injections of collodion and Berlin blue and roentgenograms after injection of sodium bromid solution appeared to show that one or more channels in the region of the tips of the minor calices were forced open, through which material in the renal pelvis flowed directly into a neighboring vein. This phenomenon apparently occurred without the slightest extravasation into the tissues. These authors made a special point of the observation that in their experiments none of the fluid was ever found higher in the tubular
Assisted suicide for the dying would reduce suffering, says Falconer
Authors: C. Dyer
Journal: BMJ (2013)

A private member’s bill to legalise physician assisted suicide for terminally ill patients in England and Wales has been tabled in the House of Lords by a former Labour lord chancellor, Charles Falconer.

The bill, which had its formal first reading on 15 May, follows the report last year of the independent Commission on Assisted Dying, chaired by Falconer, which branded the existing law “inadequate and incoherent.”1

The bill was introduced in parliament in the UK, the same week that lawyers for two paralysed men argued in the Court of Appeal that doctors should be allowed to help them end their lives. The argument was …
Increased Risk of Lower-Extremity Amputation Among Caucasian Diabetic Patients on Dialysis
Authors: Stephan Morbach, Christoph Quante, Hermann Rudolf Ochs, Franz Gaschler, Jean-Mario Pallast, Udo Knevels
Journal: Diabetes Care (2001)

In two recent issues of Diabetes Care , high amputation rates among Maori people from New Zealand (1) and Native Americans (2) with diabetes on dialysis were reported. We would like to add some information concerning Caucasians with diabetic foot syndrome and advanced renal disease from a prospective sample of 400 consecutive patients treated at our diabetic foot clinic. Similar to chronic renal insufficiency (defined by serum creatinine concentration 1.5–3.0 mg/dl), chronic renal failure and end-stage renal disease (ESRD) should be regarded as a continuum (3). We analyzed the frequency of these conditions among the entire study population and compared presentation features and outcomes among the concerned patients and among diabetic foot patients without obvious renal impairment.

At the time of presentation for the index foot lesion, 14 patients (4%, group …
Can a simple outpatient-based treatment be used to treat cutaneous leishmaniasis in young children? A Critically Appraised Topic
Authors: E. Burden-Teh, C.I. Wootton, H.C. Williams
Journal: British Journal of Dermatology (2014)

A 5-year-old boy from rural Afghanistan presented with a 1-year history of a skin lesion on his left knee, confirmed by polymerase chain reaction to be cutaneous leishmaniasis (Leishmania tropica). Conventional treatment of cutaneous leishmaniasis involves intravenous or intralesional pentavalent antimonials. The aim of this Critically Appraised Topic (CAT) is therefore to determine what alternative effective but less painful treatments (such as oral or topical therapies) can be used to treat cutaneous leishmaniasis in children. Embase and PubMed were searched for 'cutaneous leishmania*' AND 'treatment' AND 'children' in August 2014. All abstracts from April 2008 to August 2014 were reviewed. This search period was chosen to follow on from the Cochrane reviews on Old World and American leishmaniasis. Five randomized controlled trials met our inclusion criteria and have been included in this CAT. The study design and reporting quality in most of the trials included in both Cochrane reviews was found to be poor, and neither Cochrane review investigated the effect of patient age on response to treatment. This CAT identified two nonpainful treatments, topical paromomycin and oral miltefosine, whose effective use in children is supported in the literature. However, both of these treatments are currently unlicensed in the U.K. Our patient was successfully treated with miltefosine 20 mg twice daily for 4 weeks, leading to good resolution of the leishmaniasis plaque but with residual scarring.
Urinary imidazoles in rheumatoid arthritis.
Authors: E N Wardle
Journal: Annals of the Rheumatic Diseases (1969)

This is a study of a small group of patients with rheumatoid arthritis, in whom the urine excretion of imidazole compounds was examined by Figlu assay and chromatography of 12-hour urine collections following 15 g.histidine load, and by assay of 4 amino-imidazole-5 carboxamide (AIC) in 12- hour urines with and without histidine load.Gough, McCarthy, Read, Mollin, and Waters (1964) found low serum folate in one-third of cases with rheumatoid arthritis and a raised Figlu excre- tion in three quarters of these.This, they thought, was biochemical evidence of folic acid deficiency. 33per cent. of their cases had serum folates of less than 4 ng.per ml., but many other patients with fo- lates between 3 and 7 ng.per ml.had a positive Figlu result.Abnormalities of liver function in rheumatoid arthritis are known but perhaps not well recognized.Darby (1956) found abnormal bromosulphophtalein tests in 23 per cent.cases of rheumatoid disease and urine coproporphyrin was elevated in 31 per cent.cases.Proliferation of reticulo-endothelial tissue is recognized in rheumatoid disease and accounts for lymph gland enlargement, splenic enlargement, Kuppfer cell hyperplasia, and sometimes reticulum cell hyperplasia in the bone marrow (Wardle and Attan, 1967).
Prostacyclin protects against elevated blood pressure and cardiac fibrosis
Authors: Helene Francois, Krairerk Athirakul, David Howell, Rajesh Dash, Lan Mao, Hyung-Suk Kim, Howard A. Rockman, Garret A. FitzGerald, Beverly H. Koller, Thomas M. Coffman
Journal: Cell Metabolism (2005)
Symptomatic Magnesium Deficiency in Man
Authors: James F. Hammarsten, William O. Smith
Journal: New England Journal of Medicine (1957)

IT is well known that magnesium deficiency occurs in man, but it is not generally agreed that it may produce symptoms.1 For this reason it is considered worth while to present the study of a well documented case of symptomatic magnesium deficiency.Case ReportA 40-year-old man was admitted to the Oklahoma City Veterans Administration Hospital because of intermittent diarrhea of 2 years' duration. During the periods of diarrhea there were 8 to 10 watery stools daily, with small amounts of mucus and blood.Physical examination revealed a well nourished man with no unusual findings except for abdominal tenderness over . . .
Abstract 4003: Influence of extracellular calcium on MAPK signalling cascade in colon cancer cells.
Authors: Samawansha Tennakoon, Johannes Schmid, Brigitte Marian, Enikö Kallay
Journal: Cancer Research (2013)

Abstract Background: The calcium sensing receptor (CaSR) is a G-protein coupled receptor, which is capable of sensing even minute changes in extracellular calcium levels. The main role of the CaSR is regulation of calcium homeostasis. Besides the organs responsible for calcium homeostasis the receptor is expressed in a number of tissues including colonic epithelium and can be activated by several ligands, stimulating various downstream signalling pathways. Thus the CaSR is involved in numerous biological processes such as cell proliferation, differentiation and lipid membrane metabolism. Previous studies demonstrated that calcium regulates cell proliferation in colonocytes but the pathways or factors involved in this process still need to be elucidated. Aim: The aim of this study is to investigate the impact of CaSR activation on the Mitogen-Activated Protein Kinase (MAPK) signalling cascade in colon cancer cell lines. We hypothesize that in colonocytes, activated CaSR down regulates proliferative pathways. Methods: We studied the effect of CaSR ligands on downstream pathways through gene expression assays and protein analysis. Results and Conclusion: We could show that the differentiation status of the cells (TC-7 a colon cancer cell line) determines whether a pathway is activated or rather inhibited by calcium treatment. Gene expression studies performed by luciferase assay and protein analysis by western blots reflect that extracellular calcium activated MAPK cascade in subconfluent TC-7 cells. On the other hand, short time (10 to 30 minutes) treatment of confluent/ differentiated cells with extracellular calcium showed no activation of ERK. Treatment for longer time (e.g 8h) inhibited ERK phosphorylation. The treatment of the cells with 100nM R-568, a calcimimetic that act only through the CaSR slightly inhibited ERK phosphorylation compared with the vehicle control, suggesting an anti-proliferative role of the CaSR. Citation Format: Samawansha Tennakoon, Johannes Schmid, Brigitte Marian, Enikö Kallay. Influence of extracellular calcium on MAPK signalling cascade in colon cancer cells. [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 4003. doi:10.1158/1538-7445.AM2013-4003
The Major Histocompatibility Complex Gene Region and Sarcoidosis Susceptibility in African Americans
Authors: Benjamin A. Rybicki, Mary J. Maliarik, Laila M. Poisson, Roberta Sheffer, Kang Mei Chen, Marcie Major, Gary A. Chase, Michael C. Iannuzzi
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Investigators have intensively evaluated the major histocompatibility (MHC) complex for sarcoidosis susceptibility genes with the majority of reports implicating the human leukocyte antigen (HLA)-DRB1 gene. Because most studies have been performed in white and Asian populations, we sought to determine which MHC genes might be risk factors for sarcoidosis in African Americans. We genotyped six microsatellite markers spanning 11.6 megabases that overlapped the MHC region on chromosome 6p21-22 in 225 nuclear families ascertained by African American probands with a history of sarcoidosis. Using a family-based association methods approach, we performed multiallelic tests of association between each marker and sarcoidosis. A statistically significant association was detected between sarcoidosis and the DQCAR marker (p = 0.002) less than two kilobases telomeric from the HLA-DQB1 gene. Typing two additional markers in this region revealed that DQCAR-G51152 haplotypes, spanning a 38-kilobase region across the HLA-DQB1 gene, were associated with sarcoidosis on a global level (p = 0.022). Analysis of individual DQCAR and G51152 alleles showed that the DQCAR 178 (expected = 21.0; observed = 10; p = 0.0005) and G51152 217 (expected = 25.6; observed = 14; p = 0.0009) alleles were transmitted to affected offspring less often than expected; whereas the DQCAR 182 allele was transmitted more often than expected (expected = 52.6; observed = 66; p = 0.002). Our results indicate that HLA-DQB1 and not HLA-DRB1 plays an important role in sarcoidosis susceptibility in African Americans. Identification of the specific HLA-DQB1 alleles that influence sarcoidosis susceptibility in African Americans and the study of their antigenic-binding properties may reveal why African Americans suffer disproportionately from this disease.