tbuckley/cabot-search huggingface dataset:
Lymphocyte cytotoxicity to autologous hepatocytes in HBsAg positive chronic liver disease.
Authors: G Mieli-Vergani, D Vergani, B Portmann, Y White, I Murray-Lyon, J H Marigold, I Woolf, A L Eddleston, R Williams
Journal: Gut (1982)

Lymphocytes from 39 patients with HBsAg positive chronic liver disease were incubated with their own hepatocytes to investigate mechanisms of lymphocyte-mediated liver damage. Cytotoxicity was significantly increased in 46% overall, and in 73% of those with chronic active hepatitis. Unlike HBsAg negative chronic active hepatitis where only non-T cells were cytotoxic, HBsAg positive patients had both cytotoxic T and non-T cells. A purified liver membrane complex (LSP) and aggregated IgG both blocked non-T cytotoxicity without affecting T cell cytotoxicity; this suggests that the former is probably an antibody-dependent cell-mediated reaction against normal membrane components. This was confirmed in preliminary studies which demonstrated that preincubation of hepatocytes with the F(ab)29 fragment of an anti-human IgG reduced non-T lymphocyte cytotoxicity. T-cell cytotoxicity was restricted to HBeAg-positive patients, suggesting a relationship between T-cell cytotoxicity and viral replication. Purified HBsAg, however, blocked cytotoxicity in only three of 11 cases. Non-T lymphocytes reacting with normal membrane components may contribute to liver damage in both 9autoimmune9 and virus-associated chronic liver disease, whereas cytotoxic T-cells, probably reacting with viral determinants, are exclusive to those with viral replication.
Practicalities of warfare required service personnel to be vaccinated against anthrax
Authors: P. Blain, N. Lightfoot, B. Bannister
Journal: BMJ (1998)

EDITOR —Ness et al suggest that service personnel in the Gulf should be randomised to receive either active anthrax vaccination or placebo, but they fail to appreciate the issues behind the decision to give the vaccine.1 The independent Advisory Group on Medical Countermeasures assessed that there was a real …
921 Circadian rhythm in serum interleukin-6 soluble receptor (IL6sR): Temporal and functional relationship to IL6
Authors: B ROITMANJOHNSON, R SOTHERN, E KANABROCKI, J YAGER, K CORCORAN, R FUERSTENBERG, J WEATHERBEE, B NEMCHAUSKY, L SCHEVING
Journal: Journal of Allergy and Clinical Immunology (1996)
Abstract P6-04-16: Molecular Profiling of Stage II and III Breast Cancer in Latin American Women Receiving Standard-of-Care Treatment
Authors: J Gomez
Journal: Cancer Research (2010)

Abstract Breast cancer, though genetically and clinically heterogeneous, still lacks reliable prognostic and predictive markers. Gene expression profiling studies have correlated with long-term survival and response to therapy. Multiple variables thought to modify gene expression (i.e., ancestry, socio-economical and cultural factors) are not always controlled when correlating molecular markers with clinical outcome. Breast cancer rates are lower in Latin America than in other countries; molecularly, variations in gene expression should reflect different genetic and epigenetic levels there. The United States-Latin America Cancer Research Network (US-LA CRN) launches its first breast cancer pilot study in 2010 in over 20 hospitals and research facilities across Argentina, Brazil, Chile, Mexico, and Uruguay, primarily to characterize molecular profile distribution (luminal A, luminal B, HER2-like, and basal) in Latin American women with non-metastatic stage II or III breast cancer. Molecular profiles determined by microarray will be correlated with epidemiological, histological, and clinical data, including pathologic response to standard neoadjuvant chemotherapy; a molecular signature that predicts response to neoadjuvant therapy in breast cancer will be defined. This prospective cohort study will not dispense investigational drugs. Part A characterizes molecular profiles of breast cancer in Latin America; Part B examines associations between response to neoadjuvant therapy and molecular profiles. Tissue samplesfor gene expression profiling will be collected during routine core biopsies or during surgery. Core biopsies and surgical resection specimens from participants will undergo histopathologic evaluation, tumor ER, PgR, HER2, and Ki67 status assessment. During Part B, patients will be sorted by hormone receptor and HER2 status and receive standard neoadjuvant chemotherapy. Tissue samples will be re-assessed to evaluate residual cancer burden for pathologic response to neoadjuvant treatment and gene expression. Five-year patient follow-up will determine associations between molecular profiles and disease evolution after standard treatment. Besides providing data on the effectiveness of standard chemotherapy in Latin American women, study infrastructure includes establishing biobanks in participating countries to conduct additional clinical trials incorporating complex genomic and pathologic biomarkers, including trials to evaluate investigational therapies. Studying the molecular profile of breast cancer in Latin America will improve diagnosis and treatment, correlate molecular subtypes with long-term survival and response to therapy, and identify indolent-disease subpopulations of cancer patients, perhaps enabling future personalized cancer management. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-04-16.
Catecholamine Response During Human and Pork Insulin-Induced Hypoglycemia in IDDM Patients
Authors: Thomas Lingenfelser, Walter Renn, Christian Plonz, Mahmud Radjaipour, Manfred Eggstein, Bernhard Jakober
Journal: Diabetes Care (1992)

To evaluate the catecholamine response during human and pork insulin-induced hypoglycemia.Ten insulin-dependent diabetes mellitus (IDDM) patients without any signs of autonomic neuropathy received either human or pork insulin in a randomized crossover fashion on 2 nonconsecutive days. The glucose clamp technique was applied to achieve stable glycemic plateaus of 5.6, 3.3, 2.2, and 1.7 mM.The effect of both types of insulin on glucose metabolism and circulating catecholamines was almost identical. There was a sharp rise of both epinephrine (P less than 0.05) and norepinephrine (P less than 0.02) during hypoglycemia, which did not depend on the type of insulin applicated. Symptom awareness increased significantly during the decrease of blood glucose concentration. Only during developing hypoglycemia (3.3-mM plateau), was this effect more pronounced (cumulative symptom score 2 vs. 26, P less than 0.05) with pork insulin.AN attenuated catecholamine secretion seems not to be the putative mechanism of a reduced awareness of human insulin-induced hypoglycemia.
Systematic reviews in health care: Assessing the quality of controlled clinical trials
Authors: P. Juni
Journal: BMJ (2001)

This is the first in a series of four articles 

The quality of controlled trials is of obvious relevance to systematic reviews. If the “raw material” is flawed then the conclusions of systematic reviews cannot be trusted. Many reviewers formally assess the quality of primary trials by following the recommendations of the Cochrane Collaboration and other experts. 1 2 However, the methodology for both the assessment of quality and its incorporation into systematic reviews and meta-analysis are a matter of ongoing debate.3-5 In this article we discuss the concept of study quality and the methods used to assess quality.

#### Components of internal and external validity of controlled clinical trials

Internal validity —extent to which systematic error (bias) is minimised in clinical trials

Quality is a multidimensional concept, which could relate to the design, conduct, and analysis of a trial, its clinical relevance, or quality of reporting.6 The validity of the findings generated by a study clearly is an important dimension of quality. In the 1950s the social scientist Campbell proposed a useful distinction between internal and external validity (see box below). 7 8 Internal validity implies that the differences observed between groups of patients allocated to different …
Approve bevacizumab for use in eye disease in cash strapped times
Authors: I. Georgalas, C. Koutsandrea
Journal: BMJ (2012)

We agree with Godlee that the “miracle” of anti-VEGF (vascular endothelial growth factor) treatment has been overshadowed by the bevacizumab (Avastin) versus ranibuzimab (Lucentis) dispute.1

However, in our opinion, the anti-VEGF treatment versus no treatment debate is even more important. During this economic crisis, many of our patients with …
IKBKG (nuclear factor-κB essential modulator) mutation can be associated with opportunistic infection without impairing Toll-like receptor function
Authors: Bryn H. Salt, Julie E. Niemela, Rahul Pandey, Eric P. Hanson, Raquel P. Deering, Ralph Quinones, Ashish Jain, Jordan S. Orange, Erwin W. Gelfand
Journal: Journal of Allergy and Clinical Immunology (2008)
PTH-083 Management Outcomes For Patients With Positive Hepatitis C Serology Over A Three Year Period In York Hospital
Authors: JTY Ting, LL Wong, N Todd, C Millson
Journal: Gut (2014)

<h3>Introduction</h3> The majority of patients with Hepatitis C Virus (HCV) in England remain undiagnosed. There are an estimated 1298 patients infected with HCV in North Yorkshire,<sup>1</sup> but a fraction of these patients have been identified and successful treatment is rare. As part of the development process for an effective service in York, we audited existing referral patterns and outcomes for patients with a positive HCV serology test. <h3>Methods</h3> A total of 9495 patients who had HCV serology checked from January 2009 to December 2011 were identified via the York hospital microbiology database. Retrospective collection of data was performed on all patients with positive serology test, using online patient database and patients’ case notes where available. Analysis of data focused on further investigations and management of these patients. <h3>Results</h3> Out of the 9495 patients who had HCV serology tested, 330 tested positive (199 new positives, 47 known PCR positive, 1 known false-positive and 83 duplicates). Majority of the referral sources were from primary care (37%), followed by medical services (31%), drug-dependence services (9.3%), GUM (8.1%), prison (7.3%) and obstetrics (6.9%). Intravenous drug use was the most common route of acquisition. Of the 199 new positives, 113 (57%) did not receive any further investigations. 61 (31%) patients were referred to gastroenterology and 10 patients per year successfully accessed treatment. <h3>Conclusion</h3> This audit shows the majority of HCV positives had no further investigations and only 15% of patients received curative treatment. There was significant duplication of serology testing and only 72/ 199 (36%) underwent an HCV PCR, which is the next appropriate test. Throughout the UK a variety of initiatives are ongoing to increase public awareness of hepatitis C, and encourage testing. However, unless HCV service development improves, a positive test for HCV may have little or no consequence. <h3>Reference</h3> Public Health England, Hepatitis C in the UK: 2013 reportURL: //http:/www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1317139502302 <h3>Disclosure of Interest</h3> None Declared.
The Key to Unraveling the Mystery of Mortality in Heart Failure
Authors: Prakash C. Deedwania
Journal: Circulation (2003)

eart failure (HF) is a growing public health problem in the United States.Nearly 5 million Americans suffer from HF, and an estimated 550 000 new cases of HF are diagnosed each year. 1 HF is the No. 1 discharge diagnosis in patients Ն65 years of age and results in a substantial burden on healthcare expenditures.It is estimated that in 2001, more than $24 billion was spent as direct cost for the care of patients with HF. 1 Furthermore, HF is associated with a significant increase in morbidity and mortality.
Importance of the route of intravenous glucose delivery to hepatic glucose balance in the conscious dog.
Authors: B A Adkins, S R Myers, G K Hendrick, R W Stevenson, P E Williams, A D Cherrington
Journal: Journal of Clinical Investigation (1987)

To assess the importance of the route of glucose delivery in determining net hepatic glucose balance (NHGB) eight conscious overnight-fasted dogs were given glucose via the portal or a peripheral vein. NHGB was measured using the arteriovenous difference technique during a control and two 90-min glucose infusion periods. The sequence of infusions was randomized. Insulin and glucagon were held at constant basal levels using somatostatin and intraportal insulin and glucagon infusions during the control, portal, and peripheral glucose infusion periods (7 +/- 1, 7 +/- 1, 7 +/- 1 microU/ml; 100 +/- 3, 101 +/- 6, 101 +/- 3 pg/ml, respectively). In the three periods the hepatic blood flow, glucose infusion rate, arterial glucose level, hepatic glucose load, arterial-portal glucose difference and NHGB were 37 +/- 1, 34 +/- 1, 32 +/- 3 ml/kg per min; 0 +/- 0, 4.51 +/- 0.57, 4.23 +/- 0.34 mg/kg per min; 101 +/- 5, 200 +/- 15, 217 +/- 13 mg/dl; 28.5 +/- 3.5, 57.2 +/- 6.7, 54.0 +/- 6.4 mg/kg per min; +2 +/- 1, -22 +/- 3, +4 +/- 1 mg/dl; and 2.22 +/- 0.28, -1.41 +/- 0.31, and 0.08 +/- 0.23 mg/kg per min, respectively. Thus when glucose was delivered via a peripheral vein the liver did not take up glucose but when a similar glucose load was delivered intraportally the liver took up 32% (P less than 0.01) of it. In conclusion portal glucose delivery provides a signal important for the normal hepatic-peripheral distribution of a glucose load.
Stable Microreentrant Sources as a Mechanism of Atrial Fibrillation in the Isolated Sheep Heart
Authors: Ravi Mandapati, Allan Skanes, Jay Chen, Omer Berenfeld, José Jalife
Journal: Circulation (2000)

Background —Atrial fibrillation (AF) has traditionally been described as aperiodic or random. Yet, ongoing sources of high-frequency periodic activity have recently been suggested to underlie AF in the sheep heart. Our objective was to use a combination of optical and bipolar electrode recordings to identify sites of periodic activity during AF and elucidate their mechanism. Methods and Results —AF was induced by rapid pacing in the presence of 0.1 to 0.5 μmol/L acetylcholine in 7 Langendorff-perfused sheep hearts. We used simultaneous optical mapping of the right and left atria (RA and LA) and frequency sampling of optical and bipolar electrode recordings (including a roving electrode) to identify sites having the highest dominant frequency (DF). Rotors were identified from optical recordings, and their rotation period, core area, and perimeter were measured. In all, 35 AF episodes were analyzed. Mean LA and RA DFs were 14.7±3.8 and 10.3±2.1 Hz, respectively. Spatiotemporal periodicity was seen in the LA during all episodes. In 5 of 7 experiments, a single site having periodic activity at the highest DF was localized. The highest DF was most often (80%) localized to the posterior LA, near or at the pulmonary vein ostium. Rotors (n=14) were localized on the LA. The mean core perimeter and area were 10.4±2.8 mm and 3.8±2.8 mm 2 , respectively. Conclusions —Frequency sampling allows rapid identification of discrete sites of high-frequency periodic activity during AF. Stable microreentrant sources are the most likely underlying mechanism of AF in this model.
Factors Affecting Bone Mineral Density in Elderly Men Receiving Chronic In-Center Hemodialysis
Authors: BRIAN EISENBERG, ANTONIOS H. TZAMALOUKAS, GLEN H. MURATA, THERESA M. ELLIOTT, JACK E. JACKSON
Journal: Clinical Nuclear Medicine (1991)

Twenty-five elderly men receiving chronic hemodialysis had measurements of their bone mineral density (BMD) by dual-photon absorptiometry (DPA). Loss of BMD was much more pronounced in femoral necks than in lumbar vertebrae. Stepwise multiple linear-regression analysis showed that low BMD was associated with 1) hypoalbuminemia, hypermagnesemia, hyperaluminemia, and high serum alkaline phosphatase for femoral necks and 2) hypercalcemia and hypermagnesemia for lumbar vertebrae. These observations suggest that the femoral neck is the preferred site for measurement of BMD in dialysis patients. Along with factors directly affecting bone metabolism, nutritional factors may affect BMD in such patients.
Combined Ascitic Fluid and Furosemide Infusion in the Management of Ascites.
Authors: G. Eknoyan
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970Combined Ascitic Fluid and Furosemide Infusion in the Management of Ascites.G. Eknoyan, M.D., M. Martinez-Maldonado, M.D., J. J. Yium, M.D., W. N. Suki, M.D., F.A.C.P.G. Eknoyan, M.D.Search for more papers by this author, M. Martinez-Maldonado, M.D.Search for more papers by this author, J. J. Yium, M.D.Search for more papers by this author, W. N. Suki, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-793_5 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptParacentesis and the administration of diuretics to reduce the ascites of patients with cirrhosis of the liver may lead to impaired renal function. To obviate the difficulties inherent in the use of each alone, reinfusion of ascitic fluid with the simultaneous administration of mercurial or thiazide diuretics has been used. However, this results in only modest diuresis. We evaluated the use of more potent diuretics in combination with ascitic fluid infusion in the management of massive ascites.The effect of ascitic fluid infusion and furosemide administration alone and in combination was studied in eight patients with massive ascites. Ascitic fluid... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Houston, Tex. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1970Volume 72, Issue 5Page: 793-794KeywordsAscitesCirrhosisDiureticsLiver Issue Published: 1 May 1970 PDF DownloadLoading ...
Points from Letters: Reform in Medical Education
Authors: H. M. Flanagan
Journal: BMJ (1949)

<h3>Abstract</h3> Allogeneic hematopoietic cell transplantation (HCT) effectively treats high-risk hematologic diseases but can entail HCT-specific complications, which may be minimized by appropriate patient management, supported by accurate, individual risk estimation. However, almost all HCT risk scores are limited to a single risk assessment before HCT without incorporation of additional data. We developed machine learning models which integrate both baseline patient data and time-dependent laboratory measurements to individually predict mortality and cytomegalovirus (CMV) reactivation after HCT at multiple time points per patient. These gradient boosting machine models provide well-calibrated, time-dependent risk predictions and achieved areas under the receiver-operating characteristic of 0.92 and 0.83 and areas under the precision-recall curve of 0.58 and 0.62 for prediction of mortality and CMV reactivation, respectively, in a 21-day time window. Both models were successfully validated in a prospective, non-interventional study and performed on par with expert hematologists in a pilot comparison.
Quality of Outpatient Care: Diabetes-Reply
Authors: Stephen T. Parente
Journal: JAMA (1995)

<h3>In Reply.</h3> —We agree with Drs Bowman and Konen that education and patient compliance are essential ingredients to the care process. We also agree that recommended practice guidelines should not be applied blindly to all patients in all instances. However, we and others concerned with quality of primary care in the United States continue to support the premise that patient outcomes would be improved if physician groups and health plans work together to identify and monitor "essential" process and outcome indicators deemed to be generally applicable to most patients. Dr Clemenson's comments point to the critical importance of continued development of guidelines based on cost-benefit evidence. But given that this research is not now—and may never be—complete, we believe that medical leaders and those responsible for managing society's limited resources must use the best available research to offer applied guidelines to practitioners. Our clinical panels and many other national experts
Valvular Pulmonic Stenosis with Intact Ventricular Septum and Patent Foramen Ovale
Authors: MARY ALLEN ENGLE, HELEN B. TAUSSIG
Journal: Circulation (1950)

In this malformation the difficulty in sending blood through the stenosed pulmonary valve leads to right heart enlargement and to functional patency of the foramen ovale, through which a venousarterial shunt occurs. The onset of symptoms and their severity depend on the size of the opening in the pulmonary valve. Characteristic physical findings and results of fluoroscopy, electrocardiogram, circulation time, arterial blood studies, exercise test, angiocardiogram, and cardiac catheterization are presented. Diagnosis is important because these patients develop cardiac failure following at Blalock-Taussig operation, but may be greatly helped by pulmonic valvulotomy.
Uvulopalatopharyngoplasty may compromise nasal CPAP therapy in sleep apnea syndrome.
Authors: I L Mortimore, P A Bradley, J A Murray, N J Douglas
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Uvulopalatopharyngoplasty (U3P) has been advocated for treatment of snoring and sleep apnea/hypopnea syndrome (SAHS), but often it does not effect a cure, so that other therapy (CPAP) is often required. We hypothesized that patients with U3P will have increased mouth air leak during CPAP because of loss of the soft palatal seal. This may result in decreased tolerance and compliance if CPAP therapy is required after U3P. We have therefore compared CPAP tolerance in 13 awake normal male subjects, 13 male patients with SAHS and 13 male patients treated with U3P, all naive to CPAP and matched for age and body mass index. All normal subjects and patients with SAHS were able to tolerate pressures of at least 20 cm H2O without mouth air leak or appreciable discomfort. In contrast male U3P patients started to leak air via the mouth at a mean CPAP pressure of 6.8 (SD, 2.4) cm H2O and were able to tolerate a mean maximal pressure of only 14.5 (SD, 2.6) cm H2O, which was significantly less than that in the other two groups (p < 0.001). We also examined nasal CPAP compliance (machine run time) in eight patients with SAHS who had previous U3P compared with 16 patients with SAHS without U3P. Both groups were matched for age, body mass index, and apnea/hypopnea index. Patients with U3P had significantly lower compliance (mean, 3.5 h/night) compared with patients without U3P (mean, 5.7 h/night), p = 0.01. We conclude that U3P may compromise nasal CPAP therapy by increasing mouth air leak and reducing the maximal level of pressure that can be tolerated.