tbuckley/cabot-search huggingface dataset:
Costs and Cost-effectiveness of Four Treatment Regimens for Latent Tuberculosis Infection
Authors: David P. Holland, Gillian D. Sanders, Carol D. Hamilton, Jason E. Stout
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: Isoniazid given daily for 9 months is the standard treatment for latent tuberculosis infection (LTBI), but its effectiveness is limited by poor completion rates. Shorter course regimens and regimens using directly observed therapy result in improved adherence but have higher upfront costs.Objectives: To evaluate the costs and cost-effectiveness of regimens for the treatment of LTBI.Methods: We used a computerized Markov model to estimate total societal costs and benefits associated with four regimens for the treatment of LTBI: self-administered isoniazid daily for 9 months, directly observed isoniazid twice-weekly for 9 months, directly observed isoniazid plus rifapentine once weekly for 3 months, and self-administered rifampin daily for 4 months. In the base-case analysis, subjects were assumed to have newly positive tuberculin skin tests after recent exposure to infectious tuberculosis.Measurements and Main Results: We determined the costs of treatment, quality-adjusted life-years gained, and cases of active tuberculosis prevented. In the base-case analysis, rifampin dominated (less costly with increased benefits) all other regimens except isoniazid plus rifapentine, which was more effective at a cost $48,997 per quality-adjusted life year gained. Isoniazid plus rifapentine dominated all regimens at a relative risk of disease 5.2 times the baseline estimate, or with completion rates less than 34% for isoniazid or 37% for rifampin. Rifampin could be 17% less efficacious than self-administered isoniazid and still be cost-saving compared with this regimen.Conclusions: In our model, rifampin is cost-saving compared with the standard therapy of self-administered isoniazid. Isoniazid plus rifapentine is cost-saving for extremely high-risk patients and is cost-effective for lower-risk patients.
GPs are warned over unnecessary migraine referrals
Authors: G. Watts
Journal: BMJ (2011)

A consultant neurologist has warned that patients with migraine and headaches are being subjected to unnecessary high tech investigations.

Giles Elrington, a consultant neurologist at the Barts and The London NHS Trust, told a seminar at the City of London Migraine Clinic that GPs were often unduly concerned that severe headaches indicated a potentially calamitous but exceedingly rare disorder, typically a brain tumour. The result, he said, was that too many people were being subjected to further …
18F-FDG-PET/CT imaging in an IL-6- and MYC-driven mouse model of human multiple myeloma affords objective evaluation of plasma cell tumor progression and therapeutic response to the proteasome inhibitor ixazomib
Authors: K Duncan, T R Rosean, V S Tompkins, A Olivier, R Sompallae, F Zhan, G Tricot, M R Acevedo, L L B Ponto, S A Walsh, L T Tygrett, A J Berger, T Waldschmidt, H C Morse, J J Sunderland, S Janz
Journal: Blood Cancer Journal (2013)

(18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) are useful imaging modalities for evaluating tumor progression and treatment responses in genetically engineered mouse models of solid human cancers, but the potential of integrated FDG-PET/CT for assessing tumor development and new interventions in transgenic mouse models of human blood cancers such as multiple myeloma (MM) has not been demonstrated. Here we use BALB/c mice that contain the newly developed iMyc(ΔEμ) gene insertion and the widely expressed H2-L(d)-IL6 transgene to demonstrate that FDG-PET/CT affords an excellent research tool for assessing interleukin-6- and MYC-driven plasma cell tumor (PCT) development in a serial, reproducible and stage- and lesion-specific manner. We also show that FDG-PET/CT permits determination of objective drug responses in PCT-bearing mice treated with the investigational proteasome inhibitor ixazomib (MLN2238), the biologically active form of ixazomib citrate (MLN9708), that is currently in phase 3 clinical trials in MM. Overall survival of 5 of 6 ixazomib-treated mice doubled compared with mice left untreated. One outlier mouse presented with primary refractory disease. Our findings demonstrate the utility of FDG-PET/CT for preclinical MM research and suggest that this method will play an important role in the design and testing of new approaches to treat myeloma.
Role of retinol binding protein 4 in hepatic steatosis
Authors: Tetsuji Fujita
Journal: Hepatology (2013)

Using HepG2 cell, Xia et al.1 revealed that retinol binding protein 4 (RBP4) activated critical lipogenic transcription factors of sterol regulatory element-binding protein-1c (SREBP-1c) and liver X receptor through the stimulation of peroxisome proliferator-activated receptor-γ coactivator 1β (PGC-1β). The stimulatory effect of RBP4 on SREBP-1c activity associated with hepatic lipogenesis was ensured also in vivo. Xia et al. conclude that the activation of SREBP-1c by RBP4 is fully dependent on up-regulation of PGC-1β, because RBP4 did not exhibit lipogenic effect in PGC-1β-knockout mice. In the associated editorial,2 Dr. Maher raises an important question of whether RBP4 is directly linked to hepatic lipogenesis, but neither Xia et al. or Maher address the issue about the unidentified hepatic receptor of RBP4. The only known receptor for RBP4 is a receptor stimulated by retinoic acid-6 (STRA6), which is expressed in several tissues, including retina, brain, spleen, thymus, female genital tract, testis, muscle, and placental endothelial cells (and in small quantities in heart and lung), whereas STRA6 has not been identified in the liver.3 Until the discovery of the hepatic receptor of RBP4, the metabolic link between RBP4 and fat is not confirmed. Recently, Alapatt et al.4 reported that RBP4 receptor-2 (RBPR2), which is primarily expressed in the liver and intestine and induced in adipose tissue in obese mice, is likely to mediate effects of RBP4 on insulin action and glucose homeostasis in the capacity of an RBP4 receptor. To define the role of RBP4 in lipid metabolism, it would be necessary to investigate the effect of RBP4 also under the condition of knockdown of RBPR2. PGC-1β has been thought to be a coactivator of lipogenic transcription factors, leading to lipogenesis. However, a recent study suggests that PGC-1β plays dual roles in regulating hepatic fatty acid metabolism by controlling the expression of programs of genes involved in both fatty acid oxidation and de novo fatty acid synthesis, because PGC-1β-deficient mice were outwardly normal, but exhibited a significant increase in hepatic triglyceride content at 6 weeks of age.5 The lipogenic effects of RBP4 shown by Xia et al. might be time-dependent. Tetsuji Fujita, M.D. Department of Surgery Jikei University School of Medicine Tokyo, Japan
On editorial matters
Authors: U. Costabel
Journal: European Respiratory Journal (1999)

The development of the ERJ, in terms of number and quality of submitted and printed articles, has been tremendous in the first 10 yrs of its existence. Another record year for series was 1998. In the future, some restrictions are necessary, since the number of submitted manuscripts continues to rise (the forecast is about 1,350 for the end of 1998), but the number of printed pages can hardly be increased indefinitely (each single issue is now ~250 pages and is of a correct size). We are therefore forced to reduce the acceptance rate from the current 40‐ 45% to 30‐35% in the future. The Editorial Board will apply stricter criteria for acceptance, including more rigorous priority rating in regard to originality and the scientific content of submitted papers. This will ensure that only the highest quality articles are published. In the coming years, the Journal will continue to print ~3,000 pages per year, in two volumes, each volume containing six issues. Just as a reminder: in 1988, the Journal started with 10 issues and ~1,000 printed pages. The manuscripts are received from all over the world, but mainly from Europe. In 1997, as in previous years, most papers were submitted from the UK (163) an increase of almost 30%, followed by Japan (113), France (103), Germany (91), the Netherlands (90), Italy (88), USA (79), Spain (71), Canada (46), and Belgium (44), just to mention the top ten. It is clear from this increase that the
Abstract 4938: Aberrant methylation and expression of p21 on lung cancer and malignant pleural mesothelioma
Authors: Tsuyoshi Ueno, Hiromu Teramen, Shinichi Toyooka, Takafumi Kubo, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Masaomi Yamane, Takahiro Oto, Shinichiro Miyoshi
Journal: Cancer Research (2010)

Abstract Background: The cell cycle progression of which alteration is well known in human cances involves sequential activation and inactivation of cyclin-dependent kinases. The p21 (CDKN1A) plays a key role in regulating the cell cycle. Loss of expression or function of p21 (CDKN1A) has been implicated in the genesis or progression of many human malignancies. DNA methylation in tumor suppressor gene has been established as an important mechanism for gene silencing in human malignancies. In this study, we examined the methylation and expression status of P21 gene in lung cancer and malignant pleural mesothelioma (MPM). Methods: We used 14 non-small-cell lung cancer (NSCLC) cell lines and 20 primary tumors, 12 small-cell lung cancer (SCLC) cell lines, 7 MPM cell lines and 10 primary MPMs. Methylation of P21 gene was examined with methylation-specific PCR assay. p21 expression was examined by RT-PCR and western blotting. Cell lines with methylation were treated with 5-aza-CdR to confirm restoration of p21 expression. Results: Aberrant methylation of P21 was found in 20.6% of NSCLCs (28.6% and 15% in cell lines and primary NSCLCs, respectively), 8.3% of SCLC cell lines, 5.9% of MPMs (0% and 10% in MPM cell lines and primary MPMs, respectively). In NSCLC tumors, P21 methylation was detected only in smokers and squamous cell carcinoma cases but not in never smokers and adenocarinomas with bronchioloalveolar carcinoma feature. Loss of P21 mRNA expression were observed in 4 NSCLC cell lines (50.0%), 4 SCLC cell lines (33.3%) and none of MM cell lines (0%) while loss of protein expression was present in 10 NSCLC cell lines (83.3%), 6 SCLC cell lines (58.3%) and 2 MM cell lines (33.3%). mRNA expression of P21 was restored with 5-Aza-CdR treatment, indicating that methylation was responsible for silencing. These results suggested that 1) P21 methylation was one of the mechanisms of loss of P21 mRNA expression, and 2) post-transcriptional modification is responsible for loss of p21 protein expression. Conclusion: Aberrant methylation of p21 is present in lung cancer, especially for NSCLC, and rare in MPM. p21 protein expression was frequently loss in NSCLC and SCLC, partially due to DNA methylation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4938.
HLA-B27: To Type or Not to Type?
Authors: ANDREI CALIN
Journal: Annals of Internal Medicine (1980)

The association between the histocompatibility antigen HLA-B27 and the seronegative spondylarthritides such as ankylosing spondylitis and Reiter's syndrome is dramatic. A question that arises in practice is, when should a clinician request HLA-B27 typing in the assessment of a patient with a rheumatologic complaint? Generally, diagnosis of these spondylarthropathies depends on history, clinical and radiologic examination, and, occasionally, confirmatory laboratory tests. This paper reviews the criteria for the diagnosis of the spondylarthritides, discusses the sensitivity and specificity of HLA-B27 typing in these conditions, analyzes the relation between HLA-B27 status and prognosis, and defines the role of genetic counseling. It is concluded that knowledge of the patient's HLA-B27 status provides only minimal help to the physician. Indiscriminate typing is to be deprecated.
Chemical colitis induced by peracetic acid: further evidence
Authors: S. Morini, S. Campo, A. Zullo, A. Guarini, L. Ridola, C. Hassan
Journal: Endoscopy (2009)

Chemical colitis induced by peroxide agents used to sterilize endoscopes is characterized by ”snow white signs“ or ”frost signs“ appearing during colonoscopy [1] [2] [3] [4] [5] [6]. However, it remains unclear whether the colitis was really induced by the peracetic acid or, more likely, by the hydrogen peroxide [5] [6]. Peracetic acid is known to cause chemical colitis by releasing free oxygen and hydrogen radicals when in contact with the mucosa [3] [7]. Only twelve cases of chemical colitis due to peracetic acid residuals on colonoscopes have been reported [5] [7]. Recently, we observed two cases of chemical colitis in a 51-year-old woman and a 49-year-old man using a standard colonoscope (Olympus CF-Q145), which had been disinfected by peracetic acid in an automated system.
Choosing a partner in general practice.
Authors: S G Barber, K Staveley, A Down
Journal: BMJ (1991)

out in the more conducive environment of NHS facilities.We have serious doubts regarding the viability of the scrutiny team's proposals; in particular we believe that the purchasers (the prison service) will not be able to find adequate providers (NHS doctors).A corps of part time doctors devoted to the service already exists, but experience tells us that few others are likely to last the course.
Serum Creatine Kinase Level as a Screening Test for Susceptibility to Malignant Hyperthermia
Authors: Rein T. Paasuke
Journal: JAMA (1986)

One hundred thirty-one patients who were referred for muscle biopsy for in vitro contracture testing (IVCT) for susceptibility to malignant hyperthermia (MH) were studied. Serum creatine kinase (CK) levels were determined routinely before biopsy by the hospital clinical laboratories. Thirty-four had abnormal IVCTs (indicating susceptibility to MH) and 87 patients had normal IVCTs; all these 121 patients had normal CK levels. Ten additional patients had other muscle disorders (central core disease, hyperkalemic periodic paralysis, and Duchenne's muscular dystrophy) and abnormal IVCTs; six of the ten had elevated CK levels. We conclude that the serum CK level, as determined routinely, does not identify MH-susceptible individuals, but may indicate the presence of muscle disease. Therefore, the use of serum CK level as a screening or diagnostic test for susceptibility to MH should be abandoned.
Most GPs are unaware of their duties under new act
Authors: Lynn Eaton
Journal: BMJ (2004)

GPs may be surprised to find out they will need to comply with the Freedom of Information Act when it becomes law in England and Wales on 1 January 2005.

That was the message from the BMA's representative to a parliamentary select committee monitoring how effectively the new act is being introduced.

Dr John Grenville, a member of BMA General Practitioner Committee, made the statement while giving evidence last week (Tuesday 12 October) to the House of Commons Constitutional Affairs Committee.

“I think those who had read the Labour manifesto in 1997 probably thought this was about open government rather than GPs having to give information,” he said. “I do not think they followed it very closely—until they began …
Channelling new antidepressants to problem patients may be factor in fatal toxicity
Authors: E. R Heerdink
Journal: BMJ (2003)

EDITOR—Buckley and McManus provide a good overview of all reported deaths in the United Kingdom that were suspected to be due to overdosing with antidepressants over the past 15 years compared with prescription rates of the individual drugs.1 However, we seriously doubt the validity of their conclusions.

Buckley …
BMA meeting: BMA chairman demands better language checks for foreign doctors
Authors: N. Hawkes
Journal: BMJ (2010)

Doctors from abroad who work in the UK health service should face tougher checks on their competence and ability to speak English, the chairman of the BMA Council insisted as he opened the BMA conference in Brighton on Monday 28 June.

Referring to the death of David Gray, the 70 year old pensioner who was given an overdose of diamorphine out of hours by Daniel Ubani, a doctor from Germany ( BMJ 2010;340:c3326, doi:10.1136/bmj.c3326), Hamish Meldrum said, “It cannot be acceptable for poorly trained, badly regulated doctors whose knowledge of English is about as good as my knowledge of Chinese to be able to practise, virtually unchallenged, in the UK.

“My sympathy goes out to the family of David Gray, but sympathy is not enough. We must ensure that the doctors who treat our patients are competent to do so, that they have the necessary language skills, and that they are subject to the …
Ten cases of chronic ulcerative stomatitis with stratified epithelium-specific antinuclear antibody
Authors: Ernst H. Beutner, Tadeusz P. Chorzelski, Aurora Parodi, Robert Schosser, Jere Guin, Paolo P. Cardo, Ewa Maciejowska, J. Edward Valeski, Vijay Kumar
Journal: Journal of the American Academy of Dermatology (1991)
Activists call for more measured response to Tanzanian doctors' strike
Authors: P. Moszynski
Journal: BMJ (2012)

Tanzania’s fragile public healthcare system has been severely damaged by the government’s approach to industrial relations, says a group of religious leaders, opposition politicians, and trade unionists. They are calling on the government to reconsider its decision last week to dismiss 300 striking doctors to try to resolve a long running dispute over pay and conditions.

Tanzania has one of the world’s lowest ratios of doctors to population, with only one trained doctor per 30 000 people, the United Nations Development Programme says, so can ill afford to lose so much of its workforce. In the United Kingdom the proportion is one per 440 people, …
Ischemic-type biliary strictures in liver allografts: The achilles heel revisited?
Authors: Adrian Fisher, Charles M. Miller
Journal: Hepatology (1995)

Ischemic-Type Biliary Strictures in Liver Allografts:The Achilles Heel Revisited?Nonanastomotic or "ischemic-type'' biliary strictures develop in 2% to 19% of liver transplant recipient^.'.^Because these patients have considerable morbidity and mortality and increased costs, further understanding of the etiology of these strictures coupled with a method for obviating stricture formation would be a noteworthy advance in liver transplantation.Biliary strictures have been associated with prolonged cold ischemia time,1,2s4r6 hepatic artery thrombosis, ABO incompatibility, primary sclerosing cholangitis, and rejection and other immunologic injury, such as positive lymphocytotoxic crossmatches.6-'1In addition, we have demonstrated an association between prolonged preservation in University of Wisconsin solution and hepatic arterial thrombosis.12These clinical associations suggest that damage to the hepatic arterial plexus is an intermediate step in ischemic biliary strictures.Therefore, the etiology of biliary strictures is complex and multifactorial.Any or all of these associations may be operant in any single case yet inapparent in any retrospective analysis, particularly if sample size and stricture incidence are low.In addition to these clinical associations, evidence from experimental models of liver allograft injury provides additional, indirect clues to the mechanisms of biliary stricture formation.These data suggest that critical injuries incurred by the liver during cold preservation and reperfusion can be ascribed to thrombotic and ischemic events mediated by endothelial activation and injury.13,14At numerous points, the process of transplantation exposes the endothelial cells to injury: before and during cold preservation; during reperfusion, with injury mediated by platelet activating factor, reactive oxygen species, and leukocyte products; and in the posttransplantation period, with immunologic assaults.Any such injury may contribute to hepatic arteriolar arteriopathy, vasoconstriction, and subsequent segmental microvascular thrombosis.Such injuries to the endothelial cells become manifest as a global allograft injury and cause serious microcirculatory disturbance^.'^-^'Modalities that reduce endothelial injury or dilate the hepatic vasculature
Anetodermic mycosis fungoides: a new clinicopathological variant of mycosis fungoides
Authors: L. Requena, E. González-Guerra, J. Angulo, A.E. DeVore, O.P. Sangueza
Journal: British Journal of Dermatology (2007)

Journal Article Anetodermic mycosis fungoides: a new clinicopathological variant of mycosis fungoides Get access L. Requena, L. Requena Department of Dermatology, Fundación Jiménez Díaz, Universidad Autónoma, Avda. Reyes Católicos 2, 28040 Madrid, Spain *Department of Dermatology, Wake Forest University, Winston Salem, NC, U.S.A. Correspondence: Luis Requena. E‐mail: lrequena@fjd.es Search for other works by this author on: Oxford Academic Google Scholar E. González‐Guerra, E. González‐Guerra Department of Dermatology, Fundación Jiménez Díaz, Universidad Autónoma, Avda. Reyes Católicos 2, 28040 Madrid, Spain *Department of Dermatology, Wake Forest University, Winston Salem, NC, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar J. Angulo, J. Angulo Department of Dermatology, Fundación Jiménez Díaz, Universidad Autónoma, Avda. Reyes Católicos 2, 28040 Madrid, Spain *Department of Dermatology, Wake Forest University, Winston Salem, NC, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar A.E. DeVore, A.E. DeVore Department of Dermatology, Fundación Jiménez Díaz, Universidad Autónoma, Avda. Reyes Católicos 2, 28040 Madrid, Spain *Department of Dermatology, Wake Forest University, Winston Salem, NC, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar O.P. Sangueza O.P. Sangueza Department of Dermatology, Fundación Jiménez Díaz, Universidad Autónoma, Avda. Reyes Católicos 2, 28040 Madrid, Spain *Department of Dermatology, Wake Forest University, Winston Salem, NC, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 158, Issue 1, 1 January 2008, Pages 157–162, https://doi.org/10.1111/j.1365-2133.2007.08293.x Published: 01 January 2008
Longitudinal study of outcome of chronic fatigue syndrome
Authors: A Wilson, I Hickie, A Lloyd, D Hadzi-Pavlovic, C Boughton, J Dwyer, D Wakefield
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objective</b> : To examine the predictors of long term outcome for patients with the chronic fatigue syndrome. <b>Design</b> : Cohort study. <b>Subjects</b> : 139 subjects previously enrolled in two treatment trials; 103 (74%) were reassessed a mean of 3.2 years after start of the trials. <b>Setting</b> : University hospital referral centre. <b>Main outcome measures</b> : Age at onset, duration of illness, psychological and immunological status at initial assessment. Ongoing symptom severity, levels of disability, and immunological function at follow up. Results - 65 subjects had improved but only six reported no current symptoms. An alternative medical diagnosis had been made in two and psychiatric illness diagnosed in 20. The assignment of a primary psychiatric diagnosis at follow up and the strength of the belief that a physical disease process explained all symptoms at entry to the trials both predicted poor outcome. Age at onset of illness, duration of illness, neuroticism, premorbid psychiatric diagnoses, and cell mediated immune function did not predict outcome. <b>Conclusion</b> : Though most patients with the chronic fatigue syndrome improve, a substantial proportion remain functionally impaired. Psychological factors such as illness attitudes and coping style seem more important predictors of long term outcome than immunological or demographic variables.