tbuckley/cabot-search huggingface dataset:
HBsAg retention sensitizes the hepatocyte to injury by physiological concentrations of interferon-γ
Authors: Patrick N. Gilles, Deborah L. Guerrette, Richard J. Ulevitch, Robert D. Schreiber, Francis V. Chisari
Journal: Hepatology (1992)

The role that inflammatory cytokines may play in the life cycle of the hepatitis B virus and in the pathogenesis of its associated liver disease has not been carefully delineated. In this report, we demonstrate that bacterial lipopolysaccharide, a potent inducer of inflammatory cytokines in vivo , causes a severe acute liver disease in transgenic mice whose hepatocytes produce the hepatitis B virus large envelope polypeptide and retain HBsAg within the endoplasmic reticulum. In contrast, 100–fold higher doses of bacterial lipopolysaccharide do not induce liver cell injury in nontransgenic littermate controls or in transgenic mice whose hepatocytes secrete HBsAg rather than retain it. Coincident with the hepatocellular injury and the influx of inflammatory cells into the liver, a marked reduction occurs in the intrahepatic content of hepatitis B virus steady–state messenger RNA, thereby confirming the selectivity of this process for the HBsAg–positive hepatocyte. Bacterial lipopolysaccharide–induced hepatocellular injury appears to be principally mediated by interferon–γ because it can be markedly reduced by the prior administration of neutralizing interferon–γ-specific monoclonal antibodies and because recombinant interferon–γ is also selectively cytotoxic for the HBsAg–positive transgenic hepatocyte in vivo. Tumor necrosis factor-α is also involved in this process because bacterial lipopolysaccharide–induced liver cell injury is significantly reduced by tumor necrosis factor-α specific monoclonal antibodies. The role of tumor necrosis factor-α in bacterial lipopolysaccharide-induced liver cell injury is less clear than interferon–γ, however, because unlike interferon–γ it is also toxic for nontransgenic hepatocytes. These results demonstrate that the HBsAg–positive transgenic mouse hepatocyte is selectively sensitive to destruction by interferon–γ in vivo. Because this cytokine has been shown to be produced by intrahepatic lymphocytes during viral hepatitis in humans, these results raise the possibility that a similar pathway may contribute to the clearance of HBsAg–positive hepatocytes and to the pathogenesis of liver cell injury in human HBV infection as well. (Hepatology 1992;16:655-663.)
Prediction of angiographic change in native human coronary arteries and aortocoronary bypass grafts. Lipid and nonlipid factors.
Authors: D H Blankenhorn, P Alaupovic, E Wickham, H P Chin, S P Azen
Journal: Circulation (1990)

A within-group risk factor analysis was conducted to predict angiographic change in the Cholesterol Lowering Atherosclerosis Study, a randomized, placebo-controlled trial of colestipol plus niacin therapy in men with previous coronary bypass surgery. Global angiographic change, including both native coronary arteries and bypass grafts after 2 treatment years, was the end point. Risk factors included on-trial clinical measures, plasma lipids, lipoproteins, and apolipoproteins. Univariate analysis indicated that risk factors previously observed by others in epidemiologic investigation of ischemic heart disease--total cholesterol, LDL cholesterol, non-HDL cholesterol, triglycerides, apolipoprotein B, and diastolic blood pressure--had significant effects in the placebo-treated group. Univariate analysis indicated significant effects of apolipoprotein C-III in drug- and placebo-treated groups. Multivariate analysis indicated the predominant risk factor predicting the probability of global coronary progression was non-HDL cholesterol in placebo-treated subjects and the content of apolipoprotein C-III in high density lipoproteins of drug-treated subjects. Both drug- and placebo-treated group findings point to an important role for triglyceride-rich lipoproteins in progression and regression of human atherosclerosis.
Surgery is no better than a simple sling for displaced fracture of upper arm, study finds
Authors: J. Wise
Journal: BMJ (2015)

Displaced fractures in the upper arm near the shoulder can be treated just as effectively with sling immobilisation as with surgical treatment, a randomised clinical trial published in JAMA has found.1

Proximal humeral fractures account for 5-6% of all adult fractures, and most occur in people over 65. About half of these fractures are displaced, and three quarters involve the surgical neck. Surgical treatment is increasingly used for this type of fracture, contributing to higher …
Flexible Dosing For Hizentra®: Pharmacokinetic Simulations Of Various Subcutaneous Dosing Regimens and Compliance In Patients With Primary Immunodeficiency
Authors: Mikhail Rojavin, Jagdev S. Sidhu, Martin Bexon, Jonathan M. Edelman
Journal: Journal of Allergy and Clinical Immunology (2014)

Pharmacokinetic modeling and simulation analyses were performed to evaluate whether the same monthly dose of subcutaneous immunoglobulin (SCIG) can be administered in patients with primary immunodeficiency at various dosing intervals (allowing treatment flexibility) and to assess the effect of non-compliance. Simulations of SCIG dosing used a population pharmacokinetic model developed previously, based on four studies of Privigen® and Hizentra® (data from 151 unique patients). IgG concentration-time profiles and exposure metrics (steady-state area under the IgG concentration-time curve [AUC], IgG peak concentration [Cmax], and IgG trough concentration [Cmin] ratios) were simulated for various infusion intervals or missed doses. The equivalent of the weekly SCIG maintenance dose administered 1, 2, 3, 5, or 7 times/week, or biweekly (every second week) produced overlapping steady-state concentration-time profiles and similar AUC, Cmax, and Cmin ratios (95% CI were 0.98–1.03, 0.95–1.09, and 0.92–1.08, respectively). Three- and 4-weekly administration resulted in higher peaks and lower troughs; the 95% CI of the AUC, Cmax, and Cmin ratios were 0.97–1.04, 1.02–1.26, and 0.86–0.98, respectively. The reduction in median exposure due to treatment non-adherence was minimal: three consecutive missed doses, replaced at the following infusion, resulted in a drop of only 4% in the median concentration relative to consistent daily dosing (recovered within 2–3 days following resumed daily dosing). The same total monthly SCIG dose can be administered at different intervals, from daily to biweekly, with minimal impact on serum IgG levels. Lowering of trough (Cmin) with 3- and 4-weekly administrations may be clinically relevant.
Increase serum level of RCAS1 antigen in cholangiocarcinoma patients correlates with tissue level of RCAS1 MRNA and protein expression
Authors: K. Leelawat, T. Watanabe, M. Enjoji, M. Nakajima, S. Tujinda, C. Suthipintawong, V. Leardkamolkarn
Journal: Journal of Hepatology (2003)
BMA criticises delay in implementing Calman report
Authors: G D Chisholm
Journal: BMJ (1994)

EDITOR, - There is undoubtedly considerable uncertainty over that what is happening with the implementation of the Calman report. The BMA's annual representative meeting commented on delays and looked for someone to blame.1 it is important to identify where the delays have arisen.

The Working Group on Specialist Medical Training was set up in September 1992. The report was completed by February 1993 but not released until almost three months …
Plasminogen activator inhibitor type 2 is expressed in keratinocytes during re-epithelialization of epidermal defects
Authors: None Bechtel, None Wysocki, None Heidtmann, None Stark, None Fusenig, None Kramer, None Schaefer
Journal: British Journal of Dermatology (1998)

Plasminogen activation is observed in the human epidermis during re-epithelialization of epidermal defects. The activation reaction depends on plasminogen activators (PAs) associated with re-epithelializing keratinocytes. PA inhibitor type 2 (PAI-2) is thought to be a major epidermal PA inhibitor in keratinocytes. However, no data are available on the expression of PAI-2 in keratinocytes during epidermal regeneration. We have therefore analysed PAI-2 at the mRNA and protein level in keratinocyte cultures as well as in epidermal lesions in which re-epithelializing keratinocytes were apparent. We found that PAI-2 expression at the mRNA and protein level was negatively correlated with the cell density in regular keratinocyte cultures. In organotypic cocultures, in which the transition from a re-epithelializing to a sedentary phenotype can be studied, PAI-2 was most strongly expressed in early cultures prior to formation of a differentiated epidermis-like structure. We found a strong expression of PAI-2 in keratinocytes that re-epithelialized dermal burn wounds or lesions caused by the autoimmune blistering disease pemphigus vulgaris. Our results suggest that not only PAs, but also a major PA inhibitor, PAI-2, are expressed in keratinocytes that are actively involved in re-epithelialization.
Gastric Restrictive Surgery for Morbid Obesity
Authors: John G. Kral
Journal: JAMA (1985)

<h3>To the Editor.—</h3> I am writing in response to the Diagnostic and Therapeutic Technology Assessment (DATTA) report on gastric restrictive surgery for morbid obesity.<sup>1</sup>I would like to point out several inaccuracies in the text. There have been several "published reports of controlled clinical studies" of gastric bypass and gastroplasty,<sup>2-4</sup>contrary to the first sentence in the report. Also contrary to the statement in the DATTA report, gastric exclusion is<i>not</i>as effective at inducing weight reduction as intestinal bypass. Increased confusion arises when the last paragraph of the report states that "there is general agreement that these gastric restrictive operations... also... tend to be less effective at ensuring weight reduction." We know of no published data indicating that weight loss after "Mason's vertical plication" (in the literature commonly referred to as "vertical banded gastroplasty") is "less dramatic initially than with horizontal plication," no matter how this term
Metacognition, metaphors, and the measurement of human memory
Authors: Thomas O. Nelson
Journal: Behavioral and Brain Sciences (1996)

Abstract Investigations of metacognition – and also the application of the storehouse and correspondence metaphors – seem as appropriate for laboratory research as for naturalistic research. In terms of measurement, the only quantitative difference between the “input-bound percent correct” and “output-bound percent correct” is the inclusion versus exclusion (respectively) of omission errors in the denominator of the percentages.
Nerve growth factor localization in the nasal mucosa of patients with persistent allergic rhinitis
Authors: M. Bresciani, F. Lalibertè, M. F. Lalibertè, C. Gramiccioni, S. Bonini
Journal: Allergy (2008)

Background and objectives: Nerve growth factor (NGF) and NGF receptors have been shown to be expressed by structural and infiltrating inflammatory cells in the human allergic bronchial mucosa and conjunctiva. In the nose, a positive immunostaining for NGF was recently reported in biopsies of subjects undergoing surgery for refractory nasal obstruction. This study was aimed at studying by immunohistochemistry NGF expression and localization in the nasal mucosa from subjects with moderate/severe persistent allergic rhinitis and natural allergen exposure. Methods: Immunostaining for NGF, tryptase and eosinophil cationic protein was performed in human nasal turbinate sections of 25 patients affected by persistent allergic rhinitis and sensitization to Dermatophagoides pteronyssinus . Results: NGF was consistently expressed in the epithelium and in the submucosa of allergic rhinitic subjects, preferentially localized in eosinophils and mast cells. A strong NGF immunostaining was found in mucous cells of the epithelial lining and in the submucosal glands. Conclusions: As previously shown for allergic asthma and allergic conjunctivitis, NGF is also detectable in the nasal mucosa of patients with persistent allergic rhinitis. The preferential NGF localization in mucous cells of the epithelial lining and in the submucosal glands suggests a possible role for NGF in modulating secretion in allergic rhinitis and possibly other allergic diseases.
Rhabdomyolysis and acute renal failure in sickle cell anaemia.
Authors: S Devereux, S M Knowles
Journal: BMJ (1985)

Rhabdomyolysis and acute renal failure in sickle cell anaemiaAcute renal failure due to striated muscle necrosis is well recognised in a wide range of conditions.'This report concerns a patient with homozygous sickle cell disease, in whom acute renal failure was associa- ted with rhabdomyolysis during a severe sickling episode.
Efficacy of Oseltamivir-Zanamivir Combination Compared to Each Monotherapy for Seasonal Influenza: A Randomized Placebo-Controlled Trial
Authors: Xavier Duval, Sylvie van der Werf, Thierry Blanchon, Anne Mosnier, Maude Bouscambert-Duchamp, Annick Tibi, Vincent Enouf, Cécile Charlois-Ou, Corine Vincent, Laurent Andreoletti, Florence Tubach, Bruno Lina, France Mentré, Catherine Leport
Journal: PLoS Medicine (2010)

Analysis of virological and clinical outcomes from a randomized trial that was terminated early suggest that combined treatment of seasonal influenza in adult outpatients with oseltamivir plus zanamivir is no more effective than either oseltamivir or zanamivir monotherapy.
Myopathy and Rhabdomyolysis With Lovastatin Taken With Gemfibrozil
Authors: Frederick Van Lente
Journal: JAMA (1990)

<h3>To the Editor.—</h3> In their report of "Myopathy and Rhabdomyolysis Associated With Lovastatin-Gemfibrozil Combination Therapy," Pierce et al<sup>1</sup>present a case in which they describe parenthetically the presence of 44% creatine kinase—MB (CK-MB) in the serum of a patient without clear evidence of cardiac injury. Unfortunately, they did not offer further explanation for this finding. It has become increasingly clear that the process of recovery from severe skeletal muscle injury leads to an obvious change in the expression of creatine kinase isoenzymes.<sup>2</sup>However, the extent of this change has not been fully explored, and confusion remains regarding the significance of changes in the percentage of CK-MB percentage in serum. We wish to report a case that demonstrates how significantly the CK-MB percentage can increase after severe rhabdomyolysis. <h3>Report of a Case.—</h3> An 18-year-old woman underwent an unremarkable cesarean section delivery of a healthy, full-term infant following prolonged rupture
Burden of Cerebrovascular Disease in the Oxford Area in 1963 and 1964
Authors: R. M. Acheson, A. S. Fairbairn
Journal: BMJ (1970)

The only available information on the magnitude of the problem of cerebrovascular disease in England and Wales is to be found in the mortality data of the Registrar General and in the Hospital Inpatient Enquiry, which enumerates spells of illness but not the people suffering from those spells. There are no representative morbidity statistics. Data collected by the Oxford Record Linkage Study show that in 1963 from a population of 340,000 there were 427 hospital admissions among 391 patients. Of these, 34.5% were aged less than 65 years, and when patients who died at home without having entered hospital were added this figure fell to 26.7%.The survival rates at one month and one year for all strokes in the community were 43 and 30%, respectively. Married men were found to spend an average of 37 days in hospital, compared with 55 for married women; single women stayed in hospital an average of 10 days longer than single men. It is hoped that in addition to any value the overall findings may have in the planning of health services they will serve as a useful baseline in the evaluation of new methods of prophylaxis and treatment for cerebrovascular disease.
Impact of Hospitalization on the Aerobic Microflora of the Intestine.
Authors: Jack L. LeFrock
Journal: Annals of Internal Medicine (1972)

Meeting Abstracts1 May 1972Impact of Hospitalization on the Aerobic Microflora of the Intestine.Jack L. LeFrock, M.D., Charles A. Ellis, M.D., Louis Weinstein, M.D., F.A.C.P.Jack L. LeFrock, M.D.Search for more papers by this author, Charles A. Ellis, M.D.Search for more papers by this author, Louis Weinstein, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-5-872_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptUsing serial dilution techniques, pour-plates of selective media, colony counting, and standard identification methods, the total populations of fecal aerobic bacteria (coliforms, lactobacilli, fecal streptococci andMicrococcaceae) were determined in frequent serial stool samples from 75 subjects confined to the hospital for 2 weeks or more but not exposed to antibiotics. The predominant species in each population were enumerated in each stool sample. The initial coliform population in 72 of the subjects was predominantlyEscherichia coli. Subsequent analyses showed no significant change in the total number of coliforms, but by the end of 2 weeks in the hospital, only 35... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Jack L. LeFrock, M.D.; Charles A. Ellis, M.D.; Louis Weinstein, M.D., F.A.C.P.Affiliations: Boston, Mass. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1972Volume 76, Issue 5Page: 872-872KeywordsAntibioticsBacteriaEscherichia coliHospitalizationsPopulation statistics ePublished: 1 December 2008 Issue Published: 1 May 1972 PDF downloadLoading ...
Association or lack of association between tetracycline class antibiotics used for acne vulgaris and lupus erythematosus
Authors: D.J. Margolis, O. Hoffstad, W. Bilker
Journal: British Journal of Dermatology (2007)

Journal Article Association or lack of association between tetracycline class antibiotics used for acne vulgaris and lupus erythematosus Get access D.J. Margolis, D.J. Margolis Department of Biostatistics and Epidemiology and Center for Clinical Epidemiology and BiostatisticsDepartment of Dermatology, University of Pennsylvania, 815 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104, U.S.A. Correspondence: David J. Margolis. E‐mail: margo@mail.med.upenn.edu Search for other works by this author on: Oxford Academic Google Scholar O. Hoffstad, O. Hoffstad Department of Biostatistics and Epidemiology and Center for Clinical Epidemiology and Biostatistics Search for other works by this author on: Oxford Academic Google Scholar W. Bilker W. Bilker Department of Biostatistics and Epidemiology and Center for Clinical Epidemiology and Biostatistics Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 157, Issue 3, 1 September 2007, Pages 540–546, https://doi.org/10.1111/j.1365-2133.2007.08056.x Published: 01 September 2007
Sedation, surveillance, and preparation
Authors: T. Wehrmann, A. Riphaus
Journal: Endoscopy (2008)

This important meta-analysis included 36 randomized, controlled trials (RCTs) of sedation efficacy, sedation-related complications, and procedure-related efficiency outcomes in patients (n = 3918) undergoing routine upper and lower gastrointestinal endoscopy under moderate sedation. Various intravenous sedation regimens were compared. Overall, the quality of the included studies was moderate, with only 11 of the 52 RCTs fulfilling the criteria for a Jadad quality score ≥ 4 [2]. Regarding the question of whether sedation is really helpful in performing upper and lower gastrointestinal endoscopy, the authors retrieved only two RCTs that investigated the sedation efficacy and safety during esophagogastroduodenoscopy (EGD) with or without sedation; results from both trails were in favor of performing sedation. Therefore, solid-based scientific evidence enabling us to answer this question is not currently available; however, worldwide endoscopic practice has seen a substantial increase in the use of sedation during the last decade [3] [4] [5].
Large abdominal mass in Crohn's disease
Authors: M Caricato
Journal: Gut (2004)

Background: Targeting tumour necrosis factor a (TNF-a) has demonstrated efficacy in Crohn's disease.Aim: To evaluate CDP571, a humanised antibody to TNF-a, for treating active Crohn's disease.Patients: A total of 396 patients with moderate to severe Crohn's disease.Methods: In a 28 week, randomised, double blind, placebo controlled trial, patients received intravenous CDP571 (10 mg/kg) or placebo every eight weeks to week 24.The primary outcome measure was clinical response (a decrease in the Crohn's disease activity index (CDAI) to >100 points or remission (CDAI score (150 points)) at week 28.A secondary outcome measure was clinical response (using the same definition) at week 2. Results: Clinical response occurred at week 28 in 80/263 (30.4%)CDP571 patients and 31/132 (23.5%) placebo patients (p = 0.102).Clinical response at week 2 occurred in 90/263 (34.2%)CDP571 patients and 28/132 (21.2%) placebo patients (p = 0.011).Post hoc exploratory subgroup analysis of 159 patients with baseline C reactive protein (CRP) >10 mg/l demonstrated significant differences between CDP571 and placebo in clinical response rates at weeks 2 (CDP571, 50/101 (49.5%); placebo, 9/58 (15.5%); p,0.001) and 28 (CDP571, 29/101 (28.7%); placebo, 7/58 (12.1%); p = 0.018).Adverse events occurred at similar frequencies in both treatment groups.Conclusions: CDP571 is modestly effective for short but not long term treatment of unselected patients with moderate to severe Crohn's disease.The clinical relevance of this short term effect is unclear.Post hoc analysis suggests both short and long term efficacy of CDP571 in patients with elevated baseline CRP (>10 mg/l).CDP571 is well tolerated.
"Buyer beware" remains US policy towards information on the net
Authors: F. Charatan
Journal: BMJ (2002)

In the United States, no federal or state laws regulate the content of health websites on the internet. But guidelines drawn up by certain groups of healthcare experts try to ensure the integrity of health information on the internet. The most prominent of the expert groups are the Internet Health Coalition and the American Accreditation HealthCare Commission (URAC).

The Hi-Ethics code developed by the Internet Health Coalition …