tbuckley/cabot-search huggingface dataset:
Shedding light into the black box of childhood cholestatic liver disease
Authors: Lan D. A. D'Agata, Maureen M. Jonas
Journal: Hepatology (1995)

This work details the histologic findings in 84 liver biopsy specimens from 28 patients with progressive familial intrahepatic cholestasis (PFIC), who met the clinical criteria of early onset of chronic unremitting cholestasis, exclusion of any known metabolic or anatomic etiology, and low serum γ-glutamyl transpeptidase (GGTP) values. Hepato-canalicular cholestasis and disruption of the liver cell plate arrangement were early, uniform findings, and giant cell transformation was found in 56% of initial biopsies. Duct loss was a prominent finding; 70% of patients had ductal paucity, and many had abnormal bile duct epithelium, suggesting degeneration. Fibrosis was seen in the samples from 16 patients, including bridging fibrosis in specimens obtained from six patients during the first 2 years of life. Proliferating ductules at the margins of portal tracts increased as fibrosis progressed and were especially prominent in end-stage histology. Cirrhosis developed in nine of these patients and had a characteristic histologic pattern, consisting of biliary cirrhosis with diffuse stellate lobular fibrosis associated with severe cholestasis and pseudoacinar transformation. Mallory hyalin and hepatocellular carcinoma were observed in materials from some patients with advanced cirrhosis. The constellation of histologic findings in PFIC forms a recognizable pattern, and the liver histology appears to have a predictable progression. Key Words: Familial cholestasis—Byler disease—Giant cell hepatitis—Ductal paucity—Cirrhosis—Hepatocellular carcinoma. The clinical findings in 33 patients with progressive familial intrahepatic cholestasis (PFIC) are presented. Symptoms developed almost invariably before 6 months of age with severe pruritus and moderate jaundice. Other clinical findings included wheezing and nosebleeds, fat-soluble vitamin deficiency states, and cholelithiasis. Lower values for γglutamyl transpeptidase, averaging 15 IU/L before the administration of phenobarbital, and cholesterol, which averaged 156 mg/dl, are helpful in distinguishing PFIC from other pediatric cholestatic liver diseases. Autosomal recessive inheritance is probable. Twenty-six patients are alive at 12.9± 6.7 years of age, all having had successful surgical treatment, either partial biliary diversion (n = 17) or orthotopic liver transplantation (n = 10). Seven patients died at a mean age of 3.9 ± 2.4 years, as a result of liver failure in two, hepatocellular carcinoma in two, and complications of liver transplantation in three. Key Words: Byler disease-Ductal paucity-Surgical therapy for cholestatic liver disease-γGlutamy1 transpeptidase.
Amsacrine and Cisplatin in Poor Prognosis Patients with Metastatic Transitional Cell Carcinoma of the Urothelium: A Phase&amp;ndash;II Study
Authors: I. Popov, S. Jeli&acute;c, D. Radosavljevi&acute;c, Z. Nikoli&acute;c-T.
Journal: European Urology (2001)
Formalin sensitivity and differential staining of mast cells in human dermis
Authors: J.S. MARSHALL, G.P. FORD, E.B. BELL
Journal: British Journal of Dermatology (1987)

The characteristics of the human dermal mast cell population with respect to formalin fixation sensitivity, toluidine blue staining and alcian blue/safranin staining were studied. Thirty-seven specimens of normal human skin were bisected. One half was fixed in 10% neutral buffered formalin and the other in Carnoy's fixative. Sections were cut and stained with either toluidine blue or alcian blue/safranin. Significantly more mast cells were visualized with alcian blue/safranin than with toluidine blue. With both stains, only approximately 50% of the mast cells observed in the Carnoy's fixed tissue could be visualized in the formalin-fixed tissue. Alcian blue/safranin staining revealed three patterns of mast cell granule staining: mast cells containing only alcian blue-positive granules, mast cells containing only safranin-positive granules, and mast cells containing a mixture of alcian blue-positive granules and safranin-positive granules. Mast cells containing only alcian blue-positive granules constituted the majority of the dermal mast cell population and 73% of these mast cells were formalin-sensitive. Mast cells containing only safranin-positive granules and those containing a mixture of alcian blue-positive granules and safranin-positive granules showed no evidence of formalin sensitivity. The human dermal mast cell population, therefore, displays heterogeneity with respect to formalin fixation sensitivity and alcian blue/safranin staining. Dermal mast cells were visualized in significantly greater numbers in skin from the head compared with that from the body or limbs.
Human Factors in Highway Safety
Authors: Ross A. McFarland, Roland C. Moore
Journal: New England Journal of Medicine (1957)

Control of Physical Variables Influencing the DriverThe comfort, efficiency and safety of the driver are also influenced by the extent to which design features control the physical variables within the vehicle. These variables include temperature, humidity, ventilation, carbon monoxide, noise, vibration and deceleration. For each of these factors there are reasonably well defined ranges of comfort, discomfort and harmful effects.44 These limits are shown schematically in Figure 9. Temperature, humidity and ventilation. A change in any one of these variables will affect the other two so far as they determine comfort, and, hence, all three must be considered as . . .
Comparison of Effects of High-Dose and Low-Dose Aspirin on Restenosis After Femoropopliteal Percutaneous Transluminal Angioplasty
Authors: E. Minar, A. Ahmadi, R. Koppensteiner, Th. Maca, A. Stümpflen, A. Ugurluoglu, H. Ehringer
Journal: Circulation (1995)

Long-term treatment with aspirin is recommended in patients with large-vessel peripheral arterial disease since these patients have a high risk of death from cardiovascular causes. Recent studies have demonstrated the prophylactic effect of low-dose aspirin in reducing the risk of cardiovascular events. Since aspirin is also recommended for prevention of late recurrence after peripheral angioplasty, the present study was undertaken to compare the effects of high-dose (1000 mg/d) and low-dose (100 mg/d) aspirin on long-term patency after femoropopliteal angioplasty.Two hundred sixteen patients treated successfully by percutaneous transluminal angioplasty for femoropopliteal lesions were randomly allocated to therapy with either 1000 or 100 mg aspirin daily. The follow-up was 24 months. The long-term results were analyzed using the Kaplan-Meier method, and differences between curves of cumulative patency were determined with the Wilcoxon and log-rank statistics. Complete follow-up information (patency after 24 months, restenosis, and death) was obtained in 207 patients. During the 2-year follow-up period, 72 patients--36 in the high-dose and 36 in the low-dose aspirin group, respectively--developed angiographically verified reobstruction within the recanalized segment. By intention-to-treat analysis, the cumulative patency rates at 24 months were 62.5% in the high-dose and 62.6% in the low-dose aspirin group (Wilcoxon, P = .97; log-rank, P = .97). The cumulative survival at 24 months of follow-up was 86.6% in the high-dose and 87.7% in the low-dose aspirin group. The number of patients discontinuing therapy was 30 in the high-dose and 11 in the low-dose aspirin group (P < .01). Fewer patients receiving 100 mg of aspirin discontinued therapy because of gastrointestinal symptoms (4 versus 20).The data indicate that 100 mg aspirin is no less effective in the prevention of restenosis after femoropopliteal PTA than a 1000-mg dose and has fewer side effects.
Colonoscopy is the preferred colorectal cancer screening method in a population-based program
Authors: U. Marbet, P. Bauerfeind, J. Brunner, G. Dorta, J. Valloton, F. Delcò
Journal: Endoscopy (2008)

See also: Commentaire de travail de U. A. Marbet et al., pp. 650Endoscopy 2008; 40(08): 797-797DOI: 10.1055/s-0032-1306860
Abstract 2948: The role of the RNA binding protein LIN28B in neuroblastoma
Authors: John Powers, Catherine Spina, James Collins, George Daley
Journal: Cancer Research (2012)

Abstract Neuroblastoma is the most frequent extracranial solid tumor in children, accounting for almost 9% of all childhood cancers and close to 15% of childhood cancer deaths. Amplification of MYCN occurs in up to 40% of neuroblastomas, and is a marker of very poor prognosis. Current treatment strategies for MYCN amplified tumors are ineffective and in desperate need of new therapeutic avenues. The LIN28 A and B RNA binding proteins negatively regulate the let-7 family of pro-differentiation/ tumor suppressor miRNAs, enhance the translation of mRNA binding partners, and are emerging as novel onco-proteins. We show here that LIN28B is highly expressed in neuroblastoma, both in human neuroblastoma cell lines and in neuroblastoma patient samples, with an expression pattern similar to MYCN. The LIN28 proteins have been shown to directly regulate MYC, and knockdown of LIN28B in MYCN-amplified human neuroblastoma cells results in markedly reduced MYCN expression, impaired growth, greater differentiation, and reduced tumor size in mouse xenograft studies, indicating an important functional link between LIN28B and MYCN. Through LIN28B/mRNA co-immunoprecipitation we have discovered that LIN28B binds MYCN mRNA, suggesting a novel mechanism of LIN28B contribution to MYCN activity in high-risk neuroblastoma. In addition, we have also discovered that LIN28B is acetylated within its RNA binding domain, and mutational studies have suggested that modulating this post-translational modification may destabilize LIN28B protein stability. Through proteomic analysis of LIN28B -associated proteins, we have identified an acetyl-transferase as a candidate drug target for disruption of the LIN28B/MYCN oncogenic pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2948. doi:1538-7445.AM2012-2948
Hospital halves use of blood transfusion in hip surgery
Authors: R. Dobson
Journal: BMJ (2002)

A hospital that introduced a stringent transfusion policy has substantially reduced the amount of blood it uses.

The proportion of patients undergoing coronary artery bypass graft who received a transfusion fell from 57% to 45% and of patients undergoing hip replacement from 52% to 26%, with no increase in length of stay in hospital, according to a report of an audit of the use of blood after the introduction of the policy at the South Manchester University Hospital ( J …
In vitro activity of cefoxitin and imipenem against Mycobacterium abscessus complex
Authors: M. Lavollay, V. Dubée, B. Heym, J.-L. Herrmann, J.-L. Gaillard, L. Gutmann, M. Arthur, J.-L. Mainardi
Journal: Clinical Microbiology and Infection (2013)

The in vitro activity of cefoxitin and imipenem was compared for 43 strains of the Mycobacterium abscessus complex, mostly isolated from cystic fibrosis patients. The MICs of imipenem were lower than those of cefoxitin, although the number of imipenem-resistant strains was higher according to the CLSI breakpoints. Strain comparisons indicated that the MICs of cefoxitin were significantly higher for Mycobacterium bolletii than for M. abscessus. The MICs of both β-lactams were higher for the rough morphotype than for the smooth morphotype. The clinical impact of the in vitro difference between the activity of imipenem and that of cefoxitin remains to be determined.
Selection of Medical Students for Graduate Training: Pass/Fail versus Grades
Authors: Thomas J. Moss, Edward C. Deland, James V. Maloney
Journal: New England Journal of Medicine (1978)

Abstract We analyzed the performance of two cohorts of surgical residents: one from "pass/fail" and the other from "graded" medical schools. A performance index indicates that the group from graded schools performed significantly better (P<0.001). No resident from a pass/fail institution ranked above the 87th percentile, and this group accounted for 82 per cent of those ranking below the 15th percentile. A residency training program that seeks excellence among its trainees would do well to select preferentially students who apply from medical schools providing a specific class standing as part of the total evaluation of the student. It is suggested that the pass/fail controversy is symbolic of the erosion of standards that inevitably occurs when the university becomes involved in transient sociopolitical turmoil (N Engl J Med 299:25–27, 1978)
Different HLA-B27 subtypes present the same immunodominant Epstein-Barr virus peptide.
Authors: J M Brooks, R J Murray, W A Thomas, M G Kurilla, A B Rickinson
Journal: The Journal of Experimental Medicine (1993)

An immunological basis has been postulated for the strong association between at least five subtypes of the HLA-B27 allele (B27.01, .02, .04, .05, and .06) and ankylosing spondylitis, namely that cytotoxic T lymphocyte (CTL) responses are induced against an "arthritogenic" peptide that these different subtypes can all present. This requires a degree of overlap between the peptide binding repertoires of different B27 molecules. The present work, using CTL responses to Epstein-Barr virus (EBV) as a model system in which to identify B27-restricted epitopes, provides the first direct evidence that different disease-related alleles can present the same immunodominant peptide. We first noted that EBV-specific CTL clones, whether from B27.05-, B27.02-, or B27.04-positive donors, were largely subtype-specific in their restriction, recognizing only EBV-transformed B cell lines of the relevant B27 subtype. However, when tested against targets expressing individual EBV proteins from recombinant vaccinia virus vectors, all B27.05-restricted, all B27.02-restricted, and a proportion of B27.04-restricted clones were reactive to the same viral nuclear antigen, Epstein-Barr nuclear antigen (EBNA)3C. In subsequent peptide sensitization assays, all the EBNA3C-specific clones tested and also the EBNA3C-specific component within polyclonal CTL preparations from B27.05-, B27.02-, or B27.04-positive donors recognized the same immunodominant viral peptide RRIYDLIEL (EBNA3C residues 258-266). This sequence accords well with the proposed B27.05 peptide motif and clearly must be accommodated within the different peptide binding grooves of B27.05, B27.02, and B27.04 molecules. Clonal analysis revealed a second component of the B27.04-restricted response that was not shared with other subtypes. This was directed against an EBV latent membrane protein LMP2 epitope whose sequence RRRWRRLTV satisfies some but not all requirements of the B27.05 peptide motif. We conclude that there is indeed a degree of functional overlap between different B27 subtypes in their selection and presentation of CTL epitopes.
Reaccrediting general practice.
Authors: C. Nancollas
Journal: BMJ (1992)

secondary to primary care.Psychiatrists must realise this and start taking the criticisms of their clients and clients to be, the general practitioners in their area, more seriously than they do at present.This question needs to be addressed: if fundholding general practitioners are given the choice between a hospital oriented psychiatry service and other, equally effective, services that may be cheaper and are more flexible, how long before they start putting psychiatrists out of work?
Immunomodulatory effects of desloratadine: Changes in type-1/type-2 cytokine expression in PBMC cultures
Authors: Gailen D Marshall, ED Henninger, E Maniatis, Susan Y Ritter, AN Salicru, CA Messick, B Steffen, SE Marshall, D Iezzoni, Alan Harris
Journal: Journal of Allergy and Clinical Immunology (2002)
Growth in the use of antibiotics in the community in England and Scotland in 1980-93
Authors: P G Davey, R P Bax, J Newey, D Reeves, D Rutherford, R Slack, R E Warren, B Watt, J Wilson
Journal: BMJ (1996)

In 1989 the British Society for Antimicrobial Chemo-therapy set up a working party on the use of antibiotics, including a working group that was asked to identify sources of data about prescribing in general practice. The aim was to identify potential sources of data, analyse the available data, and make recommendations about further investigation.

Data about prescribing were obtained from the prescription pricing authorities in England and Scotland. In England complete data about prescriptions were available from 1980, whereas in Scotland data available before 1991 were only a 1% sample of all prescriptions. For statistical analysis the annual growth rate in prescribing in England was calculated from the following …
Diastolic heart failure
Authors: R. S Vasan
Journal: BMJ (2003)

The condition exists and needs to be recognised, prevented, and treated 

Diastolic heart failure refers to the clinical syndrome of heart failure with a preserved left ventricular ejection fraction (0.50 or more) in the absence of major valve disease.1 About a third of patients with heart failure seen by clinicians have diastolic heart failure as defined above.2 A simple classification of heart failure into systolic versus diastolic is useful because the two conditions have a distinctive pathophysiology and different prognoses.

Although diastolic heart failure is common in clinical practice worldwide,3 4 5 its existence has been questioned for several reasons. Firstly, investigators have questioned whether these patients truly have heart failure or if they actually have conditions such as obesity or pulmonary disease that can mimic heart failure.6 Doubts regarding diastolic heart failure are cast especially because the diagnosis of heart failure is partly a clinical one and prone to error. When the left ventricular ejection fraction is low the diagnosis of heart failure is seldom questioned—clinicians seem more willing to accept a diagnosis of systolic heart failure.w1 Fortunately the advent of biomarkers such plasma B-type natriuretic peptides should help confirm the presence of heart failure in patients with suspected diastolic heart failure.w2

A second area of controversy is that while investigators may agree that some patients with heart failure do have a normal ejection fraction, they doubt if the underlying mechanism …
Histidinohydroxylysinonorleucine, a trifunctional cross-link of type I collagen, in sun-exposed and sun-protected human skin
Authors: K. Okada, A. Kondo, O. Ishikawa, Y. Miyachi
Journal: British Journal of Dermatology (1997)

Journal Article Histidinohydroxylysinonorleucine, a trifunctional cross‐link of type I collagen, in sun‐exposed and sun‐protected human skin Get access K. Okada, K. Okada Department of Dermatology, Gunma University School of Medicine, Maebashi 371, Japan E‐mail: kokada@sb.gunma‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar A. Kondo, A. Kondo Department of Dermatology, Gunma University School of Medicine, Maebashi 371, Japan E‐mail: kokada@sb.gunma‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar O. Ishikawa, O. Ishikawa Department of Dermatology, Gunma University School of Medicine, Maebashi 371, Japan E‐mail: kokada@sb.gunma‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar Y. Miyachi Y. Miyachi Department of Dermatology, Gunma University School of Medicine, Maebashi 371, Japan E‐mail: kokada@sb.gunma‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 137, Issue 6, 1 December 1997, Pages 1014–1015, https://doi.org/10.1111/j.1365-2133.1997.tb01572.x Published: 01 December 1997
Active Surveillance Compared With Initial Treatment for Men With Low-Risk Prostate Cancer
Authors: Julia H. Hayes, Daniel A. Ollendorf, Steven D. Pearson, Michael J. Barry, Philip W. Kantoff, Susan T. Stewart, Vibha Bhatnagar, Christopher J. Sweeney, James E. Stahl, Pamela M. McMahon
Journal: JAMA (2010)

In the United States, 192,000 men were diagnosed as having prostate cancer in 2009, the majority with low-risk, clinically localized disease. Treatment of these cancers is associated with substantial morbidity. Active surveillance is an alternative to initial treatment, but long-term outcomes and effect on quality of life have not been well characterized.To examine the quality-of-life benefits and risks of active surveillance compared with initial treatment for men with low-risk, clinically localized prostate cancer.Decision analysis using a simulation model was performed: men were treated at diagnosis with brachytherapy, intensity-modulated radiation therapy (IMRT), or radical prostatectomy or followed up by active surveillance (a strategy of close monitoring of newly diagnosed patients with serial prostate-specific antigen measurements, digital rectal examinations, and biopsies, with treatment at disease progression or patient choice). Probabilities and utilities were derived from previous studies and literature review. In the base case, the relative risk of prostate cancer-specific death for initial treatment vs active surveillance was assumed to be 0.83. Men incurred short- and long-term adverse effects of treatment.Hypothetical cohorts of 65-year-old men newly diagnosed as having clinically localized, low-risk prostate cancer (prostate-specific antigen level <10 ng/mL, stage ≤T2a disease, and Gleason score ≤6).Quality-adjusted life expectancy (QALE).Active surveillance was associated with the greatest QALE (11.07 quality-adjusted life-years [QALYs]), followed by brachytherapy (10.57 QALYs), IMRT (10.51 QALYs), and radical prostatectomy (10.23 QALYs). Active surveillance remained associated with the highest QALE even if the relative risk of prostate cancer-specific death for initial treatment vs active surveillance was as low as 0.6. However, the QALE gains and the optimal strategy were highly dependent on individual preferences for living under active surveillance and for having been treated.Under a wide range of assumptions, for a 65-year-old man, active surveillance is a reasonable approach to low-risk prostate cancer based on QALE compared with initial treatment. However, individual preferences play a central role in the decision whether to treat or to pursue active surveillance.
Cardiac Troponins and Renal Failure
Authors: Michael S. Lauer
Journal: Circulation (2005)

n this issue of Circulation, Khan and colleagues present the results of an elegantly performed meta-analysis of the prognostic implications of elevated levels of troponin T and I among asymptomatic patients with end-stage renal disease. 1 After systematically collating the results of 28 cohort studies involving 3931 patients, they noted that an elevated troponin T level identified a group of end-stage renal disease patients with high mortality risk.Although elevated troponin I was also associated with increased risk, the exact effect size was difficult to assess because of a lack of standardization of current assays.The authors noted that despite the consistent association between elevated troponin T and mortality, the effect might be overestimated because of publication bias and study heterogeneity.Nonetheless, this meta-analysis, along with the specific reports of the largest published cohort studies, 2,3 provides robust evidence that troponin T elevation in the setting of end-stage renal disease is ominous.