tbuckley/cabot-search huggingface dataset:
Nuclear factor-κB and the hepatic inflammation-fibrosis-cancer axis
Authors: Ahmed M. Elsharkawy, Derek A. Mann
Journal: Hepatology (2007)

Nuclear factor-κB (NF-κB) is a transcriptional regulator of genes involved in immunity, inflammatory response, cell fate, and function. Recent attention has focused on the pathophysiological role of NF-κB in the diseased liver. In vivo studies using rodent models of liver disease and cell-targeted perturbation of NF-κB activity have revealed complex and multicellular functions in hepatic inflammation, fibrosis, and the development of hepatocellular carcinoma—a process we have termed the "inflammation-fibrosis-cancer axis". This review summarizes the current state of knowledge and provides insight into the vast complexity of the hepatic NF-κB signaling system, which should provide a rich source of new therapeutic targets. (HEPATOLOGY 2007;46:590–597.)
The use of bolus intravenous nitroglycerin to alter load on a beat-by-beat basis to generate left ventricular pressure-volume relationships in patients with congestive heart failure
Authors: Howard L. Haber, Eric Powers, Christopher L. Simek, Stewart Pollock, Alberto Sadun, Robert Owen, Ian J. Sarembock, Marc D. Feldman
Journal: Journal of the American College of Cardiology (1991)
Abstract 3594: Impact of metformin on HCC prognosis
Authors: Khan Akmal, Hesham Hassabo, Gehan Botrus, Neeraj Shah, Khalid Soliman, Rossa Khalaf, Donghui Li, Ahmed Kaseb, Manal Hassan
Journal: Cancer Research (2012)

Abstract Concurrent with the increase in hepatocellular carcinoma (HCC) incidence, the prevalence of metabolic syndrome has increased in the USA. Metabolic syndrome is currently considered a major health problem. Moreover, long term diabetes mellitus is an independent risk factor for HCC. We have previously shown that use of metformin among diabetics was associated with 70% risk reduction of HCC as compare to the use of other types of antidiabetic treatment. It is not known, however, if diabetic patients with HCC who used metformin had a better prognosis. Between 2001 and 2010 we interviewed 438 patients with pathologically confirmed HCC for multiple risk factors of HCC including prior history of diabetes and type of antidiabetic treatment. Survival times were calculated from the date of pathology diagnosis and were censored for patients who were alive at the last follow up. Median survival was calculated using Kaplan Meier product-limit method and survival rates were compared using the log rank test. Cox proportional hazards model (CPHM) was used to estimate the multivariate Hazard Risk Ratios (HRR) and 95% Confidence Interval (CI). Total of 130 HCC patients (29.7%) recalled prior history of diabetes with more than 1 year prior to HCC diagnosis. Most subjects were considered to have type 2 diabetes mellitus and were on an oral antidiabetic regimen. The survival duration for HCC patients with diabetes did not significantly differs from those without diabetes in men and women. However, HCC diabetic men who received metformin had a better survival outcome. The median survival was 14.9 months (95% CI, 1.3-28.9) for metformin users compared to 12.7 months (95% CI. 6.2-10.1) among HCC diabetic men who received other treatments, Log Rank p value=.04. CPHM, which included age, hepatitis C virus infection, alcohol consumption, treatment of HCC (chemotherapy and surgical treatment), history of cirrhosis, and Liver Italian Program (CLIP) staging score yielded 40% improvement of overall survival in HCC men with diabetes who received metformin as compared to other treatments. The estimated HRR (95% CI) was 0.56 (.35-.91), P =.02. These results suggest a possible beneficial role of metformin in diabetic men with HCC. Such observations need to be confirmed in other populations and with correlation with duration of metformin intake. 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 3594. doi:1538-7445.AM2012-3594
Increased Low-Density-Lipoprotein Catabolism in Myeloproliferative Disorders
Authors: HENRY GINSBERG
Journal: Annals of Internal Medicine (1982)

Hypercholesterolemia reported in patients with myeloproliferative disorders prompted our investigation of lipoprotein metabolism in these patients. The production and fractional catabolic rates of very-low-density lipoprotein (VLDL) apoprotein-B were measured using 131I-VLDL; those of VLDL triglyceride, using 3H-glycerol; and those of low-density lipoprotein (LDL) apoprotein-B, using 125I-LDL. Plasma total and LDL cholesterol levels (mean ± SD) were significantly reduced in seven patients with myeloproliferative diseases, compared to five normal subjects (93.1 ± 20.3 mg/dL versus 166.8 ± 24.6 mg/dL and 50.3 ± 14.8 mg/dL versus 107 ± 20.8 mg/dL, respectively). The production rates of VLDL apoprotein-B and VLDL triglyceride were normal in the patients. The fractional catabolic rate of LDL apoprotein-B was increased in the patients with myeloproliferative diseases (0.89 ± 0.32/d versus 0.52 ± 0.10/d;p < 0.05); this increased rate was associated with reduced plasma LDL apoprotein-B levels (41.7 ± 7.1 mg/dL versus 57.0 ± 11.3 mg/dL; p < 0.05) despite normal or elevated LDL apoprotein-B production (16.7 ± 5.3 mg/kg body weight · d versus 12.9 ± 1.2 mg/kg body weight · d). The site (or sites) of increased LDL catabolism in these hypocholesterolemic patients with myeloproliferative disorders is under investigation.
Mitochondrial One-Carbon Metabolism Maintains Redox Balance during Hypoxia
Authors: Inmaculada Martínez-Reyes, Navdeep S. Chandel
Journal: Cancer Discovery (2014)

Abstract Summary: Mitochondria generate high levels of reactive oxygen species (ROS) to activate protumorigenic signaling pathways. In parallel, the mitochondria must also increase their antioxidant capacity to lower ROS levels and prevent cancer cell death. In this issue of Cancer Discovery, Ye and colleagues demonstrate that serine catabolism through one-carbon metabolism within the mitochondrial matrix is necessary to maintain this redox balance. Cancer Discov; 4(12); 1371–3. ©2014 AACR. See related article by Ye et al., p. 1406
Activity-Dependent Dendritic Arborization Mediated by CaM-Kinase I Activation and Enhanced CREB-Dependent Transcription of Wnt-2
Authors: Gary A. Wayman, Soren Impey, Daniel Marks, Takeo Saneyoshi, Wilmon F. Grant, Victor Derkach, Thomas R. Soderling
Journal: Neuron (2006)
LOCAL APPLICATION OF SEX HORMONES
Authors: Walter Schiller
Journal: JAMA (1941)

<h3>To the Editor:—</h3> Local application of sex hormones has been attempted in occidental medicine only during the last few years. In oriental therapy evidently it was well known for centuries. The novel "The Golden Lotus" (English translation by Clemens Egerton, without date, 4 volumes, George Routledge &amp; Sons, London; German translation by Franz Kuhn under the title Kin Ping Meh, 1 volume, without date, Inselverlag, Leipzig), by Wang Shih-Cheng, who died in 1593, gives a vivid and realistic picture of Chinese life and customs at the time of the Sung dynasty in the reign of Hui Tsung 1100-1126, with numerous medical and diagnostic as well as therapeutic details. A Hindu monk reciprocates gifts from a wealthy pharmacist by presenting him with some aphrosidiac pills to be taken "one at each occasion, no more, with a drop of spirits," and a red powder to anoint the glans penis with the advice,
Workplace Secondhand Smoke Exposure in the U.S. Trucking Industry
Authors: Yueh-Hsiu Chiu, Jaime E. Hart, Donna Spiegelman, Eric Garshick, Thomas J. Smith, Douglas W. Dockery, S. Katharine Hammond, Francine Laden
Journal: Environmental Health Perspectives (2009)

Although the smoking rate in the United States is declining because of an increase of smoke-free laws, among blue-collar workers it remains higher than that among many other occupational groups.We evaluated the factors influencing workplace secondhand smoke (SHS) exposures in the U.S. unionized trucking industry.From 2003 through 2005, we measured workplace SHS exposure among 203 nonsmoking and 61 smoking workers in 25 trucking terminals. Workers in several job groups wore personal vapor-phase nicotine samplers on their lapels for two consecutive work shifts and completed a workplace SHS exposure questionnaire at the end of the personal sampling.Median nicotine level was 0.87 microg/m3 for nonsmokers and 5.96 microg/m3 for smokers. As expected, smokers experienced higher SHS exposure duration and intensity than did nonsmokers. For nonsmokers, multiple regression analyses indicated that self-reported exposure duration combined with intensity, lack of a smoking policy as reported by workers, having a nondriver job, and lower educational level were independently associated with elevated personal nicotine levels (model R2 = 0.52). Nondriver job and amount of active smoking were associated with elevated personal nicotine level in smokers, but self-reported exposure, lack of a smoking policy, and lower educational level were not.Despite movements toward smoke-free laws, this population of blue-collar workers was still exposed to workplace SHS as recently as 2005. The perceived (reported by the workers), rather than the official (reported by the terminal managers), smoking policy was associated with measured SHS exposure levels among the nonsmokers. Job duties and educational level might also be important predictors of workplace SHS exposure.
"CHOLESTEROL ESTIMATIONS IN BLOOD"
Authors: Edwin Henes
Journal: JAMA (1918)

<h3>To the Editor:</h3> —InThe Journal, Dec. 8, 1917, you comment upon "Cholesterol Estimations in Blood." The subject of cholesterinemia has occupied my attention and taken up a good deal of my time since 1912. During all these years I have made thousands of determinations and have tried most of the methods employed. Much has been said and written on the subject that is inaccurate, and the apparent inconsistencies are largely the result of improper interpretations of the results. The editorials and comments inThe Journalshould have a certain "finality" about them, and the profession ought to be able to consultThe Journalas an authority, and to take for granted its editorials and its current comments. The cholesterinemia, in the diagnosis of cholelithiasis, is far from limited in its usefulness, and the findings in this condition are far from "quite inconstant." My work has shown, and continues to
Cardiac muscarinic receptor function in rats with cirrhotic cardiomyopathy
Authors: D N Jaue, Z Ma, S S Lee
Journal: Hepatology (1997)

The pathogenesis of cirrhotic cardiomyopathy remains unclear. Because ventricular contractility is dependent on the interplay of stimulatory beta-adrenergic and inhibitory muscarinic receptors, we aimed to examine a possible role of muscarinic M2 receptor overactivity in a rat model of cirrhotic cardiomyopathy. Cirrhosis was induced by bile duct ligation (BDL), while controls underwent sham operations. Contractile responses to the muscarinic agonist carbachol were measured in situ in the autonomic-denervated pithed rat and in vitro in isolated ventricular papillary muscles. Ventricular sarcolemmal plasma membranes were isolated by sucrose density gradients, and muscarinic receptor characteristics were studied using 1-[N-methyl-3H]scopolamine (NMS). Membrane adenylyl cyclase activity was tested by a protein binding assay. Maximum first time derivative of peak ventricular systolic pressure (+dP/dt) for sham-operated and cirrhotic rats at baseline was 3,599 +/- 296 versus 1,226 +/- 63 mm Hg/sec (P < .01). Maximum first time derivative of ventricular diastolic relaxation (-dP/dt) for sham and cirrhotic rats at basal levels was -3,040 +/- 235 versus -864 +/- 59 (P < .01). The +dP/dt(max), and -dP/dt(max) responses to carbachol were blunted in the cirrhotic rats. The cirrhotic papillary muscles showed significantly less inhibition to incremental doses of carbachol than control rat muscles. Likewise, isoproterenol-stimulated membrane adenylyl cyclase activity was significantly less inhibited by carbachol doses in the cirrhotic rats. Membrane M2 receptor density and binding affinity in cirrhotic rat hearts were similar to controls. We conclude that muscarinic responsiveness was blunted in cirrhotic hearts, but this was not caused by receptor down-regulation, suggesting changes in postreceptor factors. These changes in muscarinic function are likely compensatory, and M2 receptor overactivity is not involved in the genesis of cirrhotic cardiomyopathy.
A nonlinear dosimetric model for hemoglobin adduct formation by the neurotoxic agent acrylamide and its genotoxic metabolite glycidamide.
Authors: C J Calleman, E Bergmark, L G Stern, L G Costa
Journal: Environmental Health Perspectives (1993)

Hemoglobin (Hb) adducts, formed by the neurotoxic agent acrylamide (AA) and its genotoxic metabolite glycidamide (GA), were measured in the rat by means of a method for simultaneous determination of the adducts formed to cysteine. A novel, nonlinear dosimetric model was developed to describe Hb adduct formation. This model incorporates the saturable kinetics of the metabolic conversion in vivo of AA to GA. The pharmacokinetic parameters Vmax and Km and the first-order rates of elimination, k1 and k2, for AA and GA from all processes except conversion of AA to GA, were estimated directly from Hb adduct data to 19 M hr-1, 66 microM, 0.21 hr-1, and 0.48 hr-1, respectively. At low concentrations, approximately 60% of AA was metabolized to GA. The nonlinear dosimetric model for adduct formation has potential general applicability in high-to-low-dose extrapolation of genotoxic effects.
THE EXPERT WITNESS.Read before the Michigan State Medical Society May 11-12, 1893.
Authors: F. J. GRONER
Journal: JAMA (1893)

An eminent jurist divided the medical witness into "the liar, the d——liar, and the expert witness." As much as the expert medical witness may be abused, or abuse his privilege—he has his use. Certain cases affecting the life and property of an individual, the sanity or insanity of a subject, the clearing up of mysterious deaths, and cases of poisoning require medical knowledge for their proper elucidation. Physicians from their special knowledge are likely to be called on at any time to give evidence in cases of murder, suicide, infanticide, criminal abortion, accidental death, rape, drowning and numerous other cases. But there is no class so likely to be called on the witness stand as the surgeon, unless it should be the expert neurologist. This makes some knowledge of legal medicine a necessity. Medical experts have been subjects of much severe and bitter criticism from several causes. 1. There has
Restrictive Covenants in Employment Contracts
Authors: Warren E. Whyte
Journal: JAMA (1961)

FOR THE LAST several years, one of the most popular legal subjects of inquiry by physicians has been the validity and effect of a covenant not to compete, as used in physician employment contracts. These agreements are commonly referred to as restrictive covenants. A restrictive covenant may be defined as an express provision of an employment contract which restricts the right of the employee, after the conclusion of his term of employment, to engage in a business similar to or competitive with that of the employer. Such restrictions are, in most cases, limited to a specified period of time and a specified geographical area. There can be little doubt that such covenants are common in physician employment contracts. A survey made by the American Association of Medical Clinics in 1954 revealed that 58% of the clinics contacted utilized restrictive covenants in their employment contracts. The survey also showed that
Laminar flow inhibits TNF-induced ASK1 activation by preventing dissociation of ASK1 from its inhibitor 14-3-3
Authors: Yingmei Liu, Guoyong Yin, James Surapisitchat, Bradford C. Berk, Wang Min
Journal: Journal of Clinical Investigation (2001)

The inflammatory cytokine TNF-α stimulates several presumed pro-atherogenic signaling events in endothelial cells (ECs), including activation of c-Jun NH2-terminal kinase (JNK) and induction of E-selectin. Here, we show that apoptosis signal-regulating kinase 1 (ASK1), a MAP kinase kinase kinase, is required for TNF-mediated JNK activation. TNF activates ASK1 in part by dissociating ASK1 from its inhibitor 14-3-3. Because the risk of atherosclerosis is decreased in regions of steady laminar flow, we hypothesized that laminar flow inhibits proinflammatory cytokine-mediated activation of JNK. Steady laminar flow inhibited both TNF activation of ASK1 and JNK. Inhibition of ASK1 by flow correlated with increased association of ASK1 with 14-3-3. A constitutively active form of ASK1 lacking the 14-3-3-binding site (ASK1-ΔNS967A) was not inhibited by flow. These data establish ASK1 as a target for flow-mediated inhibition of cytokine signaling and indicate a novel role for 14-3-3 as an anti-inflammatory mediator in ECs.
Strongyloides stercoralis infection in renal transplant recipients.
Authors: I V Weller, P Copland, R Gabriel
Journal: BMJ (1981)

cultures of the cerebrospinal fluid and blood grew a f3-haemolytic streptococcus not identifiable as a member of Lancefield group A, B, C, D, or G. Sensitivity plates subsequently showed the organism to be fully sensitive in vitro to both the drugs administered.Within 48 hours of this treatnent the patient's fever had resolved, and after six days of gradual improvement he regained consciousness.As soon as he was well enough to concentrate, however, he complained of tinnitus, dizziness, and deafness in both ears.Intravenous antibiotics were stopped after 10 days and phenoxymethylpenicillin, 1-5 g four times daily, with probenecid, 500 mg three times daily, were given for a further five weeks.The patient was discharged after three weeks in hospital; since then he has suffered no recurrence of meningitis but remains disabled by dizziness, unsteadiness of gait, and deafness of his right ear.The division of hospital infection (streptococcal reference) at the Public Health Service Laboratory, Colindale, identified his isolates from blood cultures and cerebrospinal fluid as Streptococcus group R (Str suis type II).
Low protein diets in chronic renal insufficiency: Authors' reply
Authors: D Fouque, M Laville, M Labeeuw, P Zech, J P Boissel, R Chifflet
Journal: BMJ (1992)

cholecystectomy, however, is generally done by one person, and it is difficult for anyone other than the operating surgeon to observe what is taking place.How do Baxter and O'Dwyer propose to teach the minilaparotomy procedure to surgeons in training, particularly iffuture trainees have little or no experience with the open operation?Perhaps the most pressing reason for leaving minilaparotomy cholecystectomy out of the equation at this stage is that it is not yet recognised as a routine procedure.
Increasing competition in NHS is hampering commissioning
Authors: Z. Kmietowicz
Journal: BMJ (2011)

The government needs to rethink some of its key policies if England’s new clinical commissioning groups are to be better at providing integrated care than their primary care trust predecessors, a new report warns.

Pro-market policies with an emphasis on increased activity and more services, rather than collaboration and care in the community, have impeded the commissioning of integrated care, says the report from the health policy think tanks the Nuffield Trust and the King’s Fund.

It acknowledges that commissioning has the power to improve outcomes and reduce costs, but primary care trusts have struggled to introduce better services, especially for patients who need urgent care, …
Audit shows that bariatric surgery is cost effective
Authors: J. Wise
Journal: BMJ (2014)

Two thirds of patients with type 2 diabetes at the time of bariatric surgery showed no indication of diabetes two years later and were able to stop their treatment, data from the National Bariatric Surgery Registry have shown.

Commenting on the report1 Clare Marx, president of the Royal College of Surgeons, said, “This audit shows compelling evidence of the cost effectiveness of bariatric surgery for obese patients. Obesity is linked with a number of conditions including diabetes which are not only debilitating for patients but also create a significant financial strain on …
Popliteal Artery Entrapment Syndrome
Authors: Gilbert R. Turner
Journal: JAMA (1969)

This is the seventh reported case of popliteal artery entrapment due to an anomalous course of the popliteal artery in relation to the medial head of the gastrocnemius muscle. This syndrome should be suspected in young male patients who have unilateral intermittent claudication without evidence of generalized arteriosclerosis. Characteristic arteriographic findings are (1) an abnormal segmental occlusion of the popliteal artery, and (2) medial deviation of the artery. Transection of the medial head of the gastrocnemius muscle and thromboendarterectomy or replacement of the popliteal artery is curative.
Use of the Dipole Moment in the Assessment of Left Ventricular Hypertrophy
Authors: R. CURTIS ELLISON, EUGENE J. FISCHMANN, OLLI S. MIETTINEN, PAUL G. HUGENHOLTZ
Journal: Circulation (1969)

A multi-electrode grid lead system, suited for the measurement of the total outward electromotive force of the heart expressed as a dipole moment, was tested in 64 subjects without heart disease and in 44 patients with left ventricular overload. The normal group showed the maximum dipole moment to the left (L-MDM) to be proportional to body weight, and by inference to left ventricular weight. For the patients with heart disease, the degree of hypertrophy was assessed in terms of LV weight derived from biplane angiocardiograms; for these patients, L-MDM was found to be proportional to LV weight (r = 0.85). The grid allowed for a more accurate assessment of LV weight than parameters obtained from the Frank lead system in the same patients. A substantially improved estimation of LV weight was achieved with both systems when body weight was considered in addition to the electrocardiographic measurements. Among the reasons for the better performance of the grid system are surface potential integration instead of sampling, consideration of individual torso dimensions, and as a result of distributed multiple electrodes, absence of distortion in the local field.
Pathological Technique. A Practical Manual for Workers in Pathological Histology and Bacteriology including Directions for the Performance of Autopsies and for Clinical Diagnosis by Laboratory Methods.
Authors: Frank Burr Mallory
Journal: JAMA (1924)

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