tbuckley/cabot-search huggingface dataset:
Serum versus intrahepatic HCV RNA and liver histology
Authors: Volker Dries, Peter Schirmacher, Hans Peter Dienes, Guido Gerken, Ralf Bartenschlager
Journal: Hepatology (2002)

recently showed depletion of mitochondrial DNA in liver from 2 patients with Navajo neuropathy (NN) and postulated that the primary defect is in nuclear regulation of mitochondrial DNA copy number.In 1997, we proposed that liver disease in children with NN may result from MDR3 deficiency (HEPATOLOGY 26(suppl):369A).Northern analysis of RNA from the liver of an affected child revealed severe reduction in MDR3 messenger RNA (mRNA) abundance (Fig. 1A), as did reversetranscription polymerase chain reaction (RT-PCR) analysis of liver biopsy samples from 3 other affected children.mRNAs for other canalicular transporters, including MDR1 and MRP2, showed no difference from normal controls.The relation between reduced MDR3 expression and the neurologic symptoms of NN was unclear.However, Northern analysis indicated that MDR3 is expressed in multiple areas of human brain (Fig. 1B).Mdr2, which is the murine form of MDR3, is expressed in the developing brain of normal mice, but is not detected in the brain or liver of mdr2Ϫ/Ϫ mice.These findings suggested that MDR3 dysfunction may also contribute to neurologic aspects of NN.To further assess whether MDR3 deficiency is a causative factor, we attempted to identify a mutation in the MDR3 gene that could account for reduced expression in NN.Although MDR3 message was severely depleted in the liver samples, a weak signal was evident by Northern and RT-PCR analysis, indicating the presence of MDR3 mRNA.Full-length complementary DNA clones were assembled from RT-PCR products generated from a patient's liver RNA.Sequence analysis of these clones failed to identify a mutation in the MDR3 mRNA, however, we could not exclude mutations in nontranscribed sequences.To determine whether mutations in MDR3 transcriptional regulatory sequences are associated with decreased mRNA levels, we obtained genomic DNA from 1 NN patient.Sequence was determined from 2.5 kb upstream of the transcriptional start site through exon 1, from the 28 MDR3 exons, and from ϳ100 to 300 nucleotides flanking each exon.No mutations were identified in these regions when the sequence of the patient was compared with that of 64 unaffected controls.These data do not exclude MDR3 as a possible causative factor in NN.Reduced levels of MDR3 expression may result from mutations in the interior of introns, more distal regions of the promoter, or a cis-acting regulatory gene located elsewhere in the genome.Alternatively, selective reduc-tion in MDR3 expression may be secondary to liver damage caused by the primary defect.The search goes on.
What Is Accountability in Health Care?
Authors: Ezekiel J. Emanuel
Journal: Annals of Internal Medicine (1996)

Accountability has become a major issue in health care. Accountability entails the procedures and processes by which one party justifies and takes responsibility for its activities. The concept of accountability contains three essential components: 1) the loci of accountability--health care consists of at least 11 different parties that can be held accountable or hold others accountable; 2) the domains of accountability--in health care, parties can be held accountable for as many as six activities: professional competence, legal and ethical conduct, financial performance, adequacy of access, public health promotion, and community benefit; and 3) the procedures of accountability, including formal and informal procedures for evaluating compliance with domains and for disseminating the evaluation and responses by the accountable parties. Different models of accountability stress different domains, evaluative criteria, loci, and procedures. We characterize and compare three dominant models of accountability: 1) the professional model, in which the individual physician and patient participate in shared decision making and physicians are held accountable to professional colleagues and to patients; 2) the economic model, in which the market is brought to bear in health care and accountability is mediated through consumer choice of providers; and 3) the political model, in which physicians and patients interact as citizen-members within a community and in which physicians are accountable to a governing board elected from the members of the community, such as the board of a managed care plan. We argue that no single model of accountability is appropriate to health care. Instead, we advocate a stratified model of accountability in which the professional model guides the physician-patient relationship, the political model operates within managed care plans and other integrated health delivery networks, and the economic and political models operate in the relations between managed care plans and other groups such as employers, government, and professional associations.
The Complementary Roles of Brain Scintigraphy and Computed Tomography in Multiple Sclerosis
Authors: ALBERT J. MORENO, JERRY M. BROWN, STEVEN F. WALLER, MICHAEL M. LUNDY, TOMMY J. BROWN
Journal: Clinical Nuclear Medicine (1983)

Cerebral computed tomography, with and without iodinated contrast, revealed the appearance and evolution of lesions in a 32–year–old man with multiple sclerosis. Two areas were enhanced with contrast, with one showing a mild mass effect and rim of enhancement. Serial brain scintigraphy using technetium–99m glucoheptonate, following the computed tomography, showed the appearance and regression of corresponding regions of increased uptake. Computed tomography one day prior to brain scintigraphy failed to demonstrate a region of increased accumulation of radiotracer. One week later, however, evidence of a corresponding unenhanced defect was noted on computed tomography. Clinical correlation is given additionally.
Children born after intracytoplasmic sperm injection: population control study
Authors: A. G Sutcliffe, B. Taylor, J. Li, S. Thornton, J G. Grudzinskas, B. A Lieberman
Journal: BMJ (1999)

Intracytoplasmic sperm injection is often successful for treatment of male infertility; over 20 000 children have been born as a result. 1 This bypassing of natural barriers to sperm selection has raised concerns about the children conceived. 2We report a population control study of children born in the United Kingdom as a result of this treatment. Subjects, methods, and resultsChildren between 12 and 24 months old who had been singleton births were identified from a list of couples who had received the treatment and their parents were invited to participate; 123 of 137 families (90%) agreed.Control children, conceived naturally, were recruited from associated nurseries (105/123) or were social peers of cases (18/123).Altogether, 123 children born after intracytoplasmic sperm injection (study children) and 123 control children were seen.Children were matched for social class, maternal educational level, region, sex, and race but not maternal age.Multiple births were excluded to avoid confounding factors.Primary outcome measures were developmental scoring on the Griffiths scales of mental development 3 and rates of congenital abnormalities.The Griffiths scales are an objective method of assessing development which uses five subscales.All subscales have a normal mean score of 100 (75-125, SD 1).Clinical data obtained included date and type of delivery, birth weight, gestation, resuscitation required, duration and reason for admission to neonatal unit (if admitted), and details of ventilatory support.Congenital abnormalities were classed according to the ICD-10 (international classification of diseases, 10th revision).Sociodemographic data obtained included date of birth, sex, and age in months.Information obtained about parents included date of birth, social class, occupation, smoking status, alcohol intake, marital or support status (that is, the number of full time carers in the household), type of housing, education, race, and mother's gravidity and parity.
The estrogenic activity of phthalate esters in vitro.
Authors: C A Harris, P Henttu, M G Parker, J P Sumpter
Journal: Environmental Health Perspectives (1997)

A large number of phthalate esters were screened for estrogenic activity using a recombinant yeast screen. a selection of these was also tested for mitogenic effect on estrogen-responsive human breast cancer cells. A small number of the commercially available phthalates tested showed extremely weak estrogenic activity. The relative potencies of these descended in the order butyl benzyl phthalate (BBP) &gt; dibutyl phthalate (DBP) &gt; diisobutyl phthalate (DIBP) &gt; diethyl phthalate (DEP) &gt; diisiononyl phthalate (DINP). Potencies ranged from approximately 1 x 10(6) to 5 x 10(7) times less than 17beta-estradiol. The phthalates that were estrogenic in the yeast screen were also mitogenic on the human breast cancer cells. Di(2-ethylhexyl) phthalate (DEHP) showed no estrogenic activity in these in vitro assays. A number of metabolites were tested, including mono-butyl phthalate, mono-benzyl phthalate, mono-ethylhexyl phthalate, mon-n-octyl phthalate; all were wound to be inactive. One of the phthalates, ditridecyl phthalate (DTDP), produced inconsistent results; one sample was weakly estrogenic, whereas another, obtained from a different source, was inactive. analysis by gel chromatography-mass spectometry showed that the preparation exhibiting estrogenic activity contained 0.5% of the ortho-isomer of bisphenol A. It is likely that the presence of this antioxidant in the phthalate standard was responsible for the generation of a dose-response curve--which was not observed with an alternative sample that had not been supplemented with o,p'-bisphenol A--in the yeast screen; hence, DTDP is probably not weakly estrogenic. The activities of simple mixtures of BBP, DBP, and 17beta-estradiol were assessed in the yeast screen. No synergism was observed, although the activities of the mixtures were approximately additive. In summary, a small number of phthalates are weakly estrogenic in vitro. No data has yet been published on whether these are also estrogenic in vitro. No data has yet been published on whether these are also estrogenic in vivo; this will require tests using different classes of vertebrates and different routes of exposure.
Dialysis solution containing hyaluronan: Effect on peritoneal permeability and inflammation in rats
Authors: Alicja Połubinska, Krzystof Pawlaczyk, Małgorzata Kużlan-Pawlaczyk, Katarzyna Wieczorowska-Tobis, Chi Chen, James B. Moberly, L. Martis, Andrzej Breçborowicz, Dimitrios G. Oreopoulos
Journal: Kidney International (2000)
Cardiac Arrhythmias: Electrophysiologic Basis for Clinical Interpretation
Authors: Robert J. Henning
Journal: JAMA (1978)

<i>Cardiac Arrhythmias</i>is written for the physician with an advanced interest in electrocardiography. The text is based on the extensive experimental and clinical observations of the two authors and endeavors to correlate abnormal electrophysiological mechanisms with specific cardiac arrhythmias. Each chapter begins with basic physiological principles and proceeds to practical clinical application. The current knowledge of membrane potentials, excitability, cardiac cell refractoriness, automaticity, excitation conduction, slow and fast currents, early and delayed afterpotentials, and the gap phenomenon is presented and discussed. Enhanced automaticity in the atrioventricular conducting system, repetitive reentry or circus movements, and delayed or after depolarizations in Purkinje fibers are described as mechanisms responsible for the genesis of ectopic tachycardias. Sinus arrest, sinoatrial block with decremental conduction, and the sick sinus syndrome is explained by examining alterations in the automaticity of the sinus node. The classification of upper, middle, and lower nodal rhythm is abandoned because most of
Prostate Cancer Screening
Authors: David Atkins
Journal: JAMA (1997)

<h3>To the Editor.</h3> —The recent article by Dr Smith and colleagues<sup>1</sup>provides important data on serial screening with prostate-specific antigen (PSA), but does little to allay the concerns expressed by many groups about widespread prostate cancer screening. The authors report that the cancer detection rate among screened men eventually decreases to approximate the population-based incidence rate, implying that screening does not result in overdiagnosis of clinically unimportant cancers. There are 2 serious problems with this argument. First, the cumulative cancer incidence among men screened for 4 years remains much higher than that in the general population due to the large number of prevelant cancers detected at the initial screening test; second, the current population-based incidence of prostate cancer itself overestimates the incidence of clinically important cancers (ie, cancers likely to cause metastasis or death). Incidence of prostate cancer in the United States has doubled in the past 10 years,
Use of mobile screening unit for diabetic retinopathy in rural and urban areas.
Authors: G P Leese, S Ahmed, R W Newton, R T Jung, A Ellingford, P Baines, S Roxburgh, J Coleiro
Journal: BMJ (1993)

To compare the effectiveness of a mobile screening unit with a non-mydriatic polaroid camera in detecting diabetic retinopathy in rural and urban areas. To estimate the cost of the service.Prospective data collection over two years of screening for diabetic retinopathy throughout Tayside.Tayside region, population 390,000, area 7770 km2.961 patients in rural areas and 1225 in urban areas who presented for screening.Presence of diabetic retinopathy, need for laser photocoagulation, age, duration of diabetes, and diabetic treatment.Compared with diabetic patients in urban areas, those in rural areas were less likely to attend a hospital based diabetic clinic (46% (442) v 86% (1054), p < 0.001); less likely to be receiving insulin (260 (27%) v 416 (34%), p < 0.001 and also after correction for differences in age distribution); more likely to have advanced (maculopathy or proliferative retinopathy) diabetic retinopathy (13% (122) v 7% (89), p < 0.001); and more likely to require urgent laser photocoagulation for previously unrecognised retinopathy (1.4% (13) v 0.5% (6), p < 0.02). The screening programme cost 10 pounds per patient screened and 1000 pounds per patient requiring laser treatment.The mobile diabetic eye screening programme detected a greater prevalence of advanced retinopathy in diabetic patients living in rural areas. Patients in rural areas were also more likely to need urgent laser photocoagulation. Present screening procedures seem to be less effective in rural areas and rural patients may benefit more from mobile screening units than urban patients.
Medicolegal Considerations In the Treatment of Mammary Lumps
Authors: JAMES G. ZIMMERLY
Journal: JAMA (1975)

IN MAY 1970, a 20-year-old woman visited her family physician's office, complaining of a lump in her left breast. She indicated that the lump had been increasing and decreasing in size over the past several weeks. The doctor described the lump as being the size of a pullet egg and discerned that the patient was due to have her next menstrual period in approximately ten days. He directed her to return in two weeks. At the end of two weeks, the patient called the physician and told him that the lump had disappeared and asked whether it was necessary for her to return. He replied that it was not. In September 1970, the woman visited a second physician, again with the complaint of a lump in the breast. An attempt to aspirate the lesion with a needle was not productive of any fluid, and a biopsy was suggested. Examination of
Reproducibility of coronary calcium measurements from multidetector computed tomography
Authors: Anthony L. Daniel, Nathan D. Wong, John D. Friedman, Sean W. Hayes, Romalisa Miranda-Peats, Rory Hachamovitch, Donna Polk, Nachum Ben-Yosef, Guido Germano, Daniel S. Berman
Journal: Journal of the American College of Cardiology (2003)
A NEW SELF-RETAINING PERINEAL RETRACTOR.
Authors: A. E. ROCKEY
Journal: JAMA (1895)

With the use of the reamer, this tissue is reamed out or cut away by the knives placed upon the sides of the instrument.They are made in three sizes; begin with the smallest and gradually enlarge, and when you have accomplished all that you can do with this size, withdraw it and introduce a larger size.The blunt probe-pointed end is introduced first and pushed in the constricted canal, a circular motion is imparted to the handle, and a mod- erate amount of pressure is exerted to cause the knives to engage upon the tissue, which at times is so hard that even the keenest knife has dif- ficulty in making an impression upon it.The instrument works very much like a pencil sharpener paring away the tissue in slices.At times the
Richard Cabot: Medical Reformer during the Progressive Era (1890-1920)
Authors: T. Andrew Dodds
Journal: Annals of Internal Medicine (1993)

Richard Cabot's (1868-1939) decision to leave full-time medical work in 1920 to teach social ethics illustrates some of the tensions inherent in twentieth-century medicine's transformation from clinical practice to a biomedical science. Cabot, then one of America's best known physicians, practiced medicine in an era in which science redefined medical practice and thinking. Although a champion of medical science, Cabot's primary concerns were clinical and humanistic. He emphasized the importance of ambulatory medicine, advocated group practice, founded hospital social work, did clinical epidemiologic research, lobbied for preventive medicine, created the Clinical-Pathologic Conference, and wrote extensively on medical ethics. In 1912, despite Cabot's great talents, a top professorship at Harvard Medical School was instead given to David Edsall, a clinician with more extensive basic science training. Cabot's efforts to define the physician's, as well as the health care system's, role in human well-being, however, presaged medicine's current attempts to emphasize the social context of the patient.
The Effects of Early and Late Scanning on Image Quality and Functional Parameters in Myocardial Perfusion Imaging
Authors: Ibrahim Albutaihi, Linda van der Veen, Arthur Scholte, Marcel P. Stokkel
Journal: Clinical Nuclear Medicine (2010)

Timing of acquisition is a factor that may influence the subdiaphragmatic activity in myocardial perfusion scintigraphy (MPS). According to the instructions of tetrofosmin, scintigraphy may already be started 15 minutes postinjection. The aim of the present study was to compare the image quality and the functional parameters between early and late scanning. Eventually, 49 consecutive patients underwent a 2-day MPS protocol in which 15 and 45 minutes after the injection of 500 MBq of technetium-99m-tetrofosmin scintigraphy both at stress and rest were performed. The amount of subdiaphragmatic tracer activity was scored from "no tracer activity" to "severe." Moderate and severe subdiaphragmatic tracer activity was considered relevant for the interpretation of the myocardial perfusion scan.Two-thirds of the patients (64%) showed a considerable amount of subdiaphragmatic activity on the 15 minutes rest images, whereas only 9 patients (18%) had considerable subdiaphragmatic activity on the late images. Stress imaging showed comparable results, however, subdiaphragmatic activity was generally less frequent and less prominent following stress. The value of the ejection fraction was significantly lower during early imaging comparing with late imaging. Lower ejection fraction was exclusively noticed in imaging with moderate and severe subdiaphragmatic tracer activity related wrong border estimation.Acquisition 15 minutes after the injection of Tetrofosmin shows a significant and clinically relevant subdiaphragmatic activity in most myocardial perfusion scans leading to poorer image quality and to an erroneous measurement of the ejection fraction. Therefore, early acquisition in MPS is not recommended in clinical practice.
Marrow Cell Egress. THE CENTRAL INTERACTION OF BARRIER PORE SIZE AND CELL MATURATION
Authors: Gerald F. Giordano, Marshall A. Lichtman
Journal: Journal of Clinical Investigation (1973)

Release of marrow cells may be determined primarily by the restrictive barrier that separates marrow hematopoietic cords from sinusoids, and by the ability of the cell to negotiate the barrier pores which are of smaller diameter than the cell. This critical interrelationship may be further modulated by humoral agents (releasing factors). To test this hypothesis, we placed human marrow cells in a chamber between millipore or nucleopore filters with pore diameters of 1-8 mum. Fixed, stained, cross sections of the filters allowed histological examination of the penetration of cells and quantification of egress of age-specific cell types. The rate of marrow granulocyte egress was highly correlated with (a) barrier pore diameter. (b) morphological age of cells, and (c) the presence of chemical attractant. Immature granulocytes would not exit through a restrictive barrier even after protracted periods and were not responsive to chemoattractants. Intermediate-aged granulocytes showed a slight ability to respond to attractants and to exit if pore diameters were large. Mature granulocytes exited through the restrictive barrier at all pore diameters studied, however, this egress was accelerated by increasing pore diameter and by the presence of an attractant. Leukemia blast cells were incapable of traversing pore diameters of 1-8 mum.These studies support the hypothesis that the development of deformability, motility, and surface receptors for chemoattractants at the later stages of granulocyte development allow the egress of cells through the marrow sinusoid wall which appears by electron microscopy to be a porous barrier with aperture diameters smaller than cell diameters; and that this process can be modulated by humoral agents which enhance directed movement of cells and may also increase pore size. Moreover, on the basis of our observations, the egress of leukemia cells is best explained by destruction of the normal sinusoid barrier of marrow indicating that manifestations of the disease are dependent on alteration in stromal as well as parenchymal marrow cells.