tbuckley/cabot-search huggingface dataset:
Liver disease associated with canalicular transport defects: Current and future therapies
Authors: Janneke M. Stapelbroek, Karel J. van Erpecum, Leo W.J. Klomp, Roderick H.J. Houwen
Journal: Journal of Hepatology (2009)

Bile formation at the canalicular membrane is a delicate process. This is illustrated by inherited liver diseases due to mutations in ATP8B1, ABCB11, ABCB4, ABCC2 and ABCG5/8, all encoding hepatocanalicular transporters. Effective treatment of these canalicular transport defects is a clinical and scientific challenge that is still ongoing. Current evidence indicates that ursodeoxycholic acid (UDCA) can be effective in selected patients with PFIC3 (ABCB4 deficiency), while rifampicin reduces pruritus in patients with PFIC1 (ATP8B1 deficiency) and PFIC2 (ABCB11 deficiency), and might abort cholestatic episodes in BRIC (mild ATP8B1 or ABCB11 deficiency). Cholestyramine is essential in the treatment of sitosterolemia (ABCG5/8 deficiency). Most patients with PFIC1 and PFIC2 will benefit from partial biliary drainage. Nevertheless liver transplantation is needed in a substantial proportion of these patients, as it is in PFIC3 patients. New developments in the treatment of canalicular transport defects by using nuclear receptors as a target, enhancing the expression of the mutated transporter protein by employing chaperones, or by mutation specific therapy show substantial promise. This review will focus on the therapy that is currently available as well as on those developments that are likely to influence clinical practice in the near future. Bile formation at the canalicular membrane is a delicate process. This is illustrated by inherited liver diseases due to mutations in ATP8B1, ABCB11, ABCB4, ABCC2 and ABCG5/8, all encoding hepatocanalicular transporters. Effective treatment of these canalicular transport defects is a clinical and scientific challenge that is still ongoing. Current evidence indicates that ursodeoxycholic acid (UDCA) can be effective in selected patients with PFIC3 (ABCB4 deficiency), while rifampicin reduces pruritus in patients with PFIC1 (ATP8B1 deficiency) and PFIC2 (ABCB11 deficiency), and might abort cholestatic episodes in BRIC (mild ATP8B1 or ABCB11 deficiency). Cholestyramine is essential in the treatment of sitosterolemia (ABCG5/8 deficiency). Most patients with PFIC1 and PFIC2 will benefit from partial biliary drainage. Nevertheless liver transplantation is needed in a substantial proportion of these patients, as it is in PFIC3 patients. New developments in the treatment of canalicular transport defects by using nuclear receptors as a target, enhancing the expression of the mutated transporter protein by employing chaperones, or by mutation specific therapy show substantial promise. This review will focus on the therapy that is currently available as well as on those developments that are likely to influence clinical practice in the near future.
Effects of feedback of information on clinical practice: a review.
Authors: M Mugford, P Banfield, M O'Hanlon
Journal: BMJ (1991)

To establish what is known about the role of feedback of statistical information in changing clinical practice.Review of 36 studies of interventions entailing the use of statistical information for audit or practice review, which used a formal research design.Papers identified from computer searches of medical and health service management publications, of which 36 describing studies of interventions designed to influence clinical care and including information feedback from clinical or administrative data systems were reviewed.Evidence for effect of information feedback on change in clinical practice.Information feedback was most likely to influence clinical practice if it was part of strategy to target decision makers who had already agreed to review their practice. A more direct effect was discernable if the information was presented close to the time of decision making. The questions of the optimum layout and quantity of information were not addressed; the 36 papers were insufficient for defining good formats for information to be used for audit or quality assurance.Given the cost of information processing and the current emphasis on closing the audit loop in the health services, it is important that the use of information in the audit process should be critically evaluated.
The Development of a Reproducible Model to Measure Clinical Performance in an Endoscopy Unit
Authors: N. Bullen, C. Challand, K. Hosie
Journal: Gut (2011)

<h3>Introduction</h3> The Darzi Report states that seven steps are required to maintain and achieve high quality standards in the NHS including the measurement and publication of the quality of clinical performance. Clinical performance is a function of quality and cost-effectiveness in a tariff-based healthcare system. Reproducible models of performance may be helpful in developing quality improvement processes. <h3>Methods</h3> Data from all endoscopy procedures performed within the main endoscopy unit at Derriford Hospital between January 2007 and December 2008 were analysed using the Endosoft database. Points were allocated as follows: two points per colonoscopy and one point for gastroscopy. A local health economic analysis revealed that ≥8 points (or 4 colonoscopies) must be performed to meet costs. An interim analysis was performed and individualised feedback given to each endoscopist on their performance and possible areas for improvement. The audit cycle was completed over the next 12 months (2008) and then repeated over the subsequent 12 months (2009). <h3>Results</h3> In total, 4371 colonoscopies were performed in 2009. (cf. 3884 in 2007, 4058 in 2008). There was an improvement in both crude Caecal Intubation Rate (CIR) from 89.6% (2007) to 90.9% (2008 and 2009), and Points/List from 8.0 (2007) to 8.2 (2008) to 8.7 (2009). ‘Clinical Performance’ was compared by plotting a capability index of individual crude CIRs against Points/List. There is a shift towards increased quality being delivered in a cost effective way. The improvement in departmental Points/List equates to an increase in unit profitability greater than 500 000 pounds. <h3>Conclusion</h3> The introduction of auditable performance measurements has dramatically improved both the quality and productivity of our endoscopy unit. <h3>Competing interests</h3> None.
Clinical course of acute infection of the upper respiratory tract in children: cohort study
Authors: C. C Butler
Journal: BMJ (2003)

dedicated obesity specialists placed at the level of the primary care trust, use of leisure services, and use of the commercial weight loss sector.We thank the dietetic managers, Chris Wyn-Jones (North Durham), Julia Smith (Newcastle Nutrition), Sue Waddington (Scarborough), and Celia Firmin (Leeds Community Dietetics) for their contribution to the study design and help to ensure its smooth running; Andy Vail (Hope Hospital, Salford
Secondary Prevention of Coronary Heart Disease in the Elderly (With Emphasis on Patients ≥75 Years of Age)
Authors: Mark A. Williams, Jerome L. Fleg, Philip A. Ades, Bernard R. Chaitman, Nancy Houston Miller, Syed M. Mohiuddin, Ira S. Ockene, C. Barr Taylor, Nanette K. Wenger
Journal: Circulation (2002)

HomeCirculationVol. 105, No. 14Secondary Prevention of Coronary Heart Disease in the Elderly (With Emphasis on Patients ≥75 Years of Age)
Clinical practice guidelines for anemia in chronic kidney disease: problems and solutions. A position statement from Kidney Disease: Improving Global Outcomes (KDIGO)
Authors: Francesco Locatelli, Allen R. Nissenson, Brendan J. Barrett, Rowan G. Walker, David C. Wheeler, Kai U. Eckardt, Norbert H. Lameire, Garabed Eknoyan
Journal: Kidney International (2008)
Prevalence of diabetes among Native Americans and Alaska Natives, 1990-1997: an increasing burden.
Authors: N R Burrows, L S Geiss, M M Engelgau, K J Acton
Journal: Diabetes Care (2000)

To determine trends in diabetes prevalence among Native Americans and Alaska Natives.From 1990 to 1997, Native Americans and Alaska Natives with diabetes were identified from the Indian Health Service (IHS) national outpatient database, and prevalence was calculated using these cases and estimates of the Native American and Alaskan population served by IHS and tribal health facilities. Prevalence was age-adjusted by the direct method based on the 1980 U.S. population.Between 1990 and 1997, the number of Native Americans and Alaska Natives of all ages with diagnosed diabetes increased from 43,262 to 64,474 individuals. Prevalence of diagnosed diabetes increased by 29%. By 1997, prevalence among Native Americans and Alaska Natives was 5.4%, and the age-adjusted prevalence was 8.0%. During the entire 1990-1997 period, prevalence among women was higher than that among men, but the rate of increase was higher among men than women (37 vs. 25%). In 1997, age-adjusted prevalence of diabetes varied by region and ranged from 3% in the Alaska region to 17% in the Atlantic region. The increase in prevalence between 1990 and 1997 ranged from 16% in the Northern Plains region to 76% in the Alaska region.Diabetes is common among Native Americans and Alaska Natives, and it increased substantially during the 8-year period examined. Effective interventions for primary, secondary, and tertiary, prevention are needed to address the substantial and rapidly growing burden of diabetes among Native Americans and Alaska Natives.
Nuclear Threat: What About the Russians?
Authors: Arvid K. Deusenberg
Journal: JAMA (1985)

To the Editor.—  Certainly no one I know is in favor of nuclear war. I am acquainted, however, with the broadest range of opinions as  how such a war can best be avoided. Some of these appeared in your Aug 2,1985, issue.  Volumes could, and should, be written about comments made and conclusions drawn, but in the interest of brevity, I include two observations:  Cassel et al 1 quote the Soviet physicians' oath, then promptly fail  take any note of the most significant phrase in the script: to be guided in all my actions by the principles of  morality. Even a cursory consultation of the works and speeches of the originators of Soviet communism, as well as a similar examination of the works and speeches of their present-day successors in power, would have informed these correspondents that Communist  is that morality that benefits the state, or,
Childhood cancer and power lines: Results depend on chosen control group
Authors: Leeka Kheifets, Maria Feychting, Joachim Schüz
Journal: BMJ (2005)

Childhood cancer and power linesWhat do the data mean?Editor-Draper et al used distance of mother's home from high voltage overhead transmission lines (predominantly 275 kV and 400 kV) at the time of her child's birth as a proxy for her child's subsequent exposure to power-frequency magnetic fields (reviewed by Ahlbom et al). 1 2 As they acknowledge, this is a crude estimate since, in contrast to other reports, 2 no household measurements were taken, no data on more prevalent low voltage distribution sources were collected, no information from other time points in the child's life was obtained, variations during the 33 years period studied were not considered, and no validatory home visits were carried out.A recent report into residential exposures to magnetic fields in the United Kingdom estimated that proximity to high voltage lines, 275 kV and above, explained only 9% of those with measurements ≥ 0.2 microtesla ( T). 3 National data on the distribution of houses in relation to high voltage lines in the UK were provided (J Swanson, National Grid Transco, personal communication, 2000) to the UK Childhood Cancer Study (UKCCS) Group for its study of power lines and childhood cancer, to assess the representativeness of study subjects. 4 An equivalent comparison using National Grid data spanning the far longer period investigated in the paper by Draper et al was not undertaken.The assessments of distance to power lines in the UKCCS were made for all registered controls, who have been shown to represent the general population. 5plot of the distributions of the leukaemia and non-leukaemia cases and controls in the study by Draper et al, national populations, and UKCCS populations by distance from high voltage lines (figure) seems to show that the leukaemia controls used in the analysis presented by Draper et al are systematically different.Their positive result over 100 m may therefore be explained not by an excess of cases but by a deficit of controls in the early years of the study.
Commentary: ordinary misery should not be mistaken for pathology
Authors: S. White
Journal: BMJ (1997)

Child mental health: who is responsible?The labelling of all childhood ills as mental health problems diverts doctors into child welfare work that is more properly the province of social services or education, argues child psychiatrist Robert Goodman.The result, he claims, is that many children who could have benefited from medical assessment and treatment for their emotional and behavioural problems do not get that help.We asked another child psychiatrist, an educational psychologist, and a social worker to respond to Dr Goodman's challenge. An overextended remit Robert GoodmanParents and teachers are seriously dissatisfied with the behaviour of many children.Other children experience considerable stress, misery, or anxiety.Epidemiological studies suggest that roughly 20% of all children and teenagers are maladjusted or distressed, 1 with some estimates being substantially higher. 2 In the child psychiatric literature and government strategy documents these maladjusted and distressed children are referred to as having psychiatric disorders or mental health problems. 3 4I believe that this medicalisation of all maladjustment and distress is a serious "own goal" for the health service, generating unrealistic expectations of what child mental health services can deliver and diverting health professionals from their areas of expertise.The medicalisation of maladjustment and distress is enshrined in the contemporary psychiatric classifications of the World Health Organisation and the American Psychiatric Association. 5 6Perhaps both these classifications were overinfluenced by the World Health Organisation's otherworldly definition of health as "a state of complete physical, mental and social wellbeing, and not merely the absence of disease and infirmity" 7 ; falling short of this ideal is then a lack of health, and it is only a small step to define any serious shortfall as a disease.Cynics will also note that the medicalisation of maladjustment and distress generates employment for doctors and persuades health insurers to foot at least some of the bill.An overinclusive notion of child mental health may have encouraged health providers to fill the vacuum as successive funding crises have led social services and education to withdraw from much of their traditional child and family guidance work.Antisocial behaviour in adults is usually seen as a social problem: similar behaviour in children is often categorised as a mental health problem
Genes means pancreatitis
Authors: D C WHITCOMB
Journal: Gut (1999)

See article on page 259 

Identifying the molecular mechanisms responsible for acute and chronic pancreatitis in humans is one of the most difficult problems in modern science. Major obstacles include the inaccessibility of the human pancreas to observation, the unpredictability of disease onset, the non-specific nature of abdominal pain early in the course of acute pancreatitis, an inability to biopsy the pancreas safely, difficulty in distinguishing initiating events from the concomitant inflammatory response, and the obvious problems of investigating a tissue that self-destructs during the disease process. Even fundamental questions as to whether pancreatitis begins in the acinar cell or through pathology related to the pancreatic ducts continue to be debated.1 2 Animal models also fail to provide critical insights, partly because of the artificial methods used to induce pancreatitis.3-5 

The discovery of the mutations in the cationic trypsinogen gene responsible for hereditary forms of pancreatitis in American and European kindreds6 7 provided tremendous insights into the mechanism of acute and chronic pancreatitis …
MEDICINE AND RELIGION A NEW JOURNAL DEPARTMENT
Authors: Paul S. Rhoads
Journal: JAMA (1967)

Through ages physicians have wrestled with the moral and ethical issues which are inherent in the care of patients. Clinicians have long pondered dilemmas such as these: How far should one go in maintaining the life of a patient facing an inevitably fatal termination from widespread cancer, and what should one say to such a patient? What are the ultimate goals that make the long preparation and hard work required of the physician worth all the effort? What part should the physician be prepared to play in helping persons in trouble from marital dissension, sex problems of adolescence, alcoholism, etc? In the present era of advanced medical technology, such problems as the following have come to the fore: Under what circumstances should the hospital resuscitation team undertake to restore circulation when there has been cardiac arrest, and how long should these efforts continue? How is one to resolve the moral
Regulating incremental innovation in medical devices
Authors: A. S. Kesselheim, P. V. Rajan
Journal: BMJ (2014)

Patients need active regulatory oversight, linked to compulsory post-marketing research

As therapeutic options, medical devices differ from prescription drugs in many ways, but one of the most important is their potential for rapid evolution in basic design or technology. In the context of prescription drugs, it would be completely unreasonable to take a basic chemical structure, add another methyl group to it, and presume the drug would work the same (or better) without subjecting the new molecule to additional clinical testing. Medical devices, by contrast, change often. In a study published earlier this year, we found that cardiac implantable electronic devices approved in the US had a median of 50 applications to the Food and Drug Administration (FDA) for big and small changes over their median 15 year regulatory lifespans.1

In a linked paper (doi:10.1136/bmj.g5133), Nieuwenhuijse and colleagues provide important insights into the evidence base supporting new versions of hip and knee replacement devices.2 After conducting a systematic review of the literature and registry data, they found no good evidence of improved clinical outcomes for five widely used and marketed “advances” in hip and knee replacement technology, but they …
D2-40 lymphatic marker for detecting lymphatic invasion in thin to intermediate thickness melanomas: Association with sentinel lymph node status and prognostic value—A retrospective case study
Authors: Laurel E. Fohn, Adrian Rodriguez, Mark C. Kelley, Fei Ye, Yu Shyr, George Stricklin, Jason B. Robbins
Journal: Journal of the American Academy of Dermatology (2011)
Elevated Tribbles homolog 2–specific antibody levels in narcolepsy patients
Authors: Vesna Cvetkovic-Lopes, Laurence Bayer, Stéphane Dorsaz, Stéphanie Maret, Sylvain Pradervand, Yves Dauvilliers, Michel Lecendreux, Gert-Jan Lammers, Claire E.H.M. Donjacour, Renaud A. Du Pasquier, Corinne Pfister, Brice Petit, Hyun Hor, Michel Mühlethaler, Mehdi Tafti
Journal: Journal of Clinical Investigation (2010)

Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and attacks of muscle atonia triggered by strong emotions (cataplexy). Narcolepsy is caused by hypocretin (orexin) deficiency, paralleled by a dramatic loss in hypothalamic hypocretin-producing neurons. It is believed that narcolepsy is an autoimmune disorder, although definitive proof of this, such as the presence of autoantibodies, is still lacking. We engineered a transgenic mouse model to identify peptides enriched within hypocretin-producing neurons that could serve as potential autoimmune targets. Initial analysis indicated that the transcript encoding Tribbles homolog 2 (Trib2), previously identified as an autoantigen in autoimmune uveitis, was enriched in hypocretin neurons in these mice. ELISA analysis showed that sera from narcolepsy patients with cataplexy had higher Trib2-specific antibody titers compared with either normal controls or patients with idiopathic hypersomnia, multiple sclerosis, or other inflammatory neurological disorders. Trib2-specific antibody titers were highest early after narcolepsy onset, sharply decreased within 2-3 years, and then stabilized at levels substantially higher than that of controls for up to 30 years. High Trib2-specific antibody titers correlated with the severity of cataplexy. Serum of a patient showed specific immunoreactivity with over 86% of hypocretin neurons in the mouse hypothalamus. Thus, we have identified reactive autoantibodies in human narcolepsy, providing evidence that narcolepsy is an autoimmune disorder.
Atlas of Technics in Surgery
Authors: M. Michael Eisenberg
Journal: JAMA (1965)

<b>The Craft of Surgery</b>. 2 vol. Edited by Philip Cooper. 1,510 pp, 1,040 illus. $42.50. Little, Brown &amp; Co.. 34 Beacon St, Boston 6, 1964 It is highly improbable that a truly definitive atlas of surgical technique will ever be available to the practicing surgeon; nor is this a particularly lamentable deficit. It is to be expected that while a basic and unified approach to many surgical problems has evolved, the details and niceties of most general operative procedures have an infinite variety of refinements, far too numerous to be encompassed by a single text. Consequently, books on the art and craft of surgery are rarely competitive but rather are complementary. And so it is with two recently published texts, one written by Madden and the other edited by Cooper. Madden's<i>Atlas of Technics in Surgery</i>is an expanded two-volume second edition of a highly successful text which first appeared in 1958 as a single tome. Each procedure illustrated is depicted by the artist as the author performs it. One virtue of this type of
Structural Adaptation of the Nuclear Pore Complex in Stem Cell–Derived Cardiomyocytes
Authors: Carmen Perez-Terzic, Atta Behfar, Annabelle Méry, Jan M.A. van Deursen, Andre Terzic, Michel Pucéat
Journal: Circulation Research (2003)

Macromolecules are transported in and out of the nucleus through nuclear pores. It is poorly understood how these megadalton conduits support nucleocytoplasmic traffic during genetic reprogramming associated with cell commitment to a specific lineage. Murine embryonic stem cells were differentiated into cardiomyocytes within embryoid bodies, and contracting cells expressing myocardial-specific proteins were isolated from the mesodermal layer. Compared with postmitotic cardiac cells from heart muscle, these proliferative and differentiating stem cell-derived cardiomyocytes demonstrated a significantly lower density of nuclear pores. At nanoscale resolution, the pore channel was commonly unoccupied in heart muscle-isolated cardiac cells, yet a dense material, presumably the central transporter, protruded toward the cytosolic face of the nuclear pore complex in stem cell-derived cardiomyocytes. Stem cell-derived cardiac cells distributed the nuclear transport factor Ran in the nucleus, decreased the number of spare nuclear pore complexes from the cytosolic annulate lamellae reservoir, and expressed a set of nucleoporins, NUP214, NUP358, NUP153, and p62, involved in nuclear transport. Stem cell-derived cardiomyocytes secured transport of nuclear constitutive proteins, cardiogenic transcription factors, and cell cycle regulators, including the prototypic histone H1, myocyte enhancer binding factor 2, and p53. Thus, differentiating stem cell-derived cardiomyocytes undergo structural adaptation and mobilize nuclear transport regulators in support of nucleocytoplasmic communication during commitment to mature cardiac lineage.