tbuckley/cabot-search huggingface dataset:
Sterol absorption--from lumen to liver.
Authors: N McIntyre
Journal: Gut (1971)

Progress reportSterol absorption-from lumen to liver Sterols are compounds of great biological importance which are found in animals and plants'.They are insoluble in water and are chemically rather unreactive and these qualities are appropriate to their role as structural components of cellular membranes.Cholesterol is the predominant mammalian sterol but biosynthetic precursors such as lathosterol and 7- dehydrocholesterol are present in significant amounts in the intestinal mucosa, skin, and other tissues.The major plant sterols are ,B-sitosterol, campesterol, and stigmasterol.Sterols are present in large amounts in mammalian diets.The content of individual sterols in a diet depends, among other things, on the relative proportions of foodstuffs of plant and animal origin.Following ingestion exogenous sterol is mixed in stomach and small intestine with endogenous sterol; the latter is mainly cholesterol which is added in bile and shed epithelial cells but in some animals endogenous sterols are also ingested during groom- ing of the skin2.The bulk of dietary sterol is present as the free alcohol but a variable proportion of both plant and animal sterols is present in the form of steryl esters which are hydrolysed in the gut by the pancreatic enzyme cholesterol esterase3.The contents of the small intestine can normally be separated by ultra- centrifugation into three phases: sediment, supranatant emulsion, and an aqueous micellar phase.The mixed micelles of the last phase are water- soluble polymolecular aggregates of bile salts, monoglycerides, fatty acids, and phospholipids; they are capable of dissolving water-insoluble organic compounds such as sterols within their hydrocarbon core4.It is usually stated that the sterols in the small intestinal lumen are distributed between the emulsion and micellar phases5 but this conclusion was reached on the basis of experiments in which large amounts of triglyceride were fed.In rats fed a normal laboratory diet little evidence of a significant emulsion was found and the bulk of intraluminal sterol was found in the sediment6.Sterols can also be found in the small intestinal sediment in man7 and it is likely that the importance of the emulsion phase in sterol absorption has been overemphasized.At varying levels of the rat small intestine the micellar sterol pattern was found to be similar to that of the sediment6.This suggests that different sterols have a similar solubility in micelles and also that sedi- ment sterol is available for absorption.As micellar solution is obligatory for mucosal uptake of sterols3 absorption can take place only from the small intestine and it is now clear that it is the upper small intestine which is quantitatively most important.In this area hydrolysis of triglycerides provides relatively large amounts of mono- glycerides and fatty acids for incorporation into mixed micelles; this increases the amount of sterol which can be held in solution and thsWs the amount available for absorption.Less monoglyceride and fatty acids are generated
Coronary Angioscopic Findings in the Infarct-Related Vessel Within 1 Month of Acute Myocardial Infarction
Authors: Eric Van Belle, Jean-Marc Lablanche, Christophe Bauters, Nathalie Renaud, Eugène P. McFadden, Michel E. Bertrand
Journal: Circulation (1998)

Limited angioscopic information is available on the natural history of infarct-related plaque after myocardial infarction (MI), in particular the effect of thrombolysis.We studied with angioscopy the morphological characteristics of the infarct-related lesion in 56 patients between 24 hours and 4 weeks after MI. Forty of these patients were initially treated with a thrombolytic agent. Most lesions were complex (complex + ulcerated shape = 54%). The predominant color of the plaque was yellow in 79% of cases; only 6% were uniformly white. Angioscopically visible thrombus was found in 77% of cases. Despite angioscopic evidence of instability, only 7% of the patients had post-MI angina. During the 1-month time window since the occurrence of MI, there was no significant difference in the angioscopic appearance of the plaque except for a slight increase in uniformly white plaques (P=.07). The use of a thrombolytic agent at the onset of MI was associated with a reduction in thrombus size and less protruding thrombi (P=.02) but not with a decreased frequency of plaque containing thrombi. Furthermore, a trend for more frequently ulcerated plaques (45% versus 16%, P=.06) was associated with the use of a thrombolytic agent.These results suggest that healing of the infarct-related lesion requires more than 1 month and that an "unstable" yellow plaque with adherent thrombus is common during that period. This finding may partly explain the unique behavior of recent infarct-related lesions, which are more prone to occlude than other lesions.
WORKS AND NOT WORDS.An Appeal from Mr. Bok to the Medical Profession.
Authors: Edward Bok
Journal: JAMA (1905)

Philadelphia, May 15, 1905. <h3>To the Editor:</h3> —During the last year I have received hundreds of letters from physicians in every part of the United States commending the attitude of the<i>Ladies' Home Journal</i>in its efforts to awaken the public to an understanding of the patent medicine curse. Scores of commendatory resolutions from medical associations have likewise come to our company. All these have been gladly received and appreciated, and our acknowledgments in each case have tried to express this fullest feeling of satisfaction. It is, therefore, with no lack of appreciation that I say that, while these individual and association commendations have been pleasant, I could wish the sentiments therein expressed might have resulted in some effective co-operative work. What I mean is this: During the past winter there was introduced into the legislatures of not less than fourteen states bills which had for their object the regulation
Germline mutations of the BRCA1 gene in breast and ovarian cancer families provide evidence for a genotype–phenotype correlation
Authors: Simon A. Gayther, William Warren, Sylvie Mazoyer, Paul A. Russell, Patricia A. Harrington, Mathias Chiano, Sheila Seal, Rifat Hamoudi, Elizabeth J. van Rensburg, Alison M. Dunning, Richard Love, Gareth Evans, Doug Easton, David Clayton, Michael R. Stratton, Bruce A.J. Ponder
Journal: Nature Genetics (1995)
An Unusual Type of Spiculated Erythrocyte in Metastatic Liver Disease and Hemolytic Anemia
Authors: JAMES W. KELLER
Journal: Annals of Internal Medicine (1971)

A patient had hemolytic anemia associated with spiculated erythrocytes and massive hepatic metastases from rectal carcinoid. The patient's erythrocytes resembled acanthocytes found in abetalipoproteinemia when examined by scanning electron microscopy. The patient's erythrocytes contained normal quantities of cholesterol, and his serum did not transform normal erythrocytes into spiculated cells in vitro. Normal erythrocytes infused into the patient did not acquire the filtration properties of acanthocytes, yet their survival was shortened, suggesting that the mechanism of hemolysis was independent of acanthocyte formation. These findings are discussed in relation to the acanthocytes found in other liver diseases. The great variability in results obtained studying the mechanism of acanthocyte formation suggest that multiple factors may lead to their formation.
Some Practical Observations on the Best Methods of Introducing the Catheter in Cases of Extremely Narrow and Irritable Stricture
Authors: H. Thompson
Journal: BMJ (1857)

pital Reports, in which these cysts have ulcerated, and the con- tents been poured into the neighbouring cavities, the peritoneum, the large intestine, etc.None of these cases, however, is exactly parallel to the foregoing.Most, if not all of them, were taken to be, malignant.This character was, to say the least, very doubtful in the present case, the only indication of it being the character of the fluitl, a microscopic examination of which (lid not muclh tendl to confirm such an opinion.In those of Dr. Bright's cases in which the laceration was not the result of violence, it seemed to proceetl from the distension of the sac and pressure of the enclosCed fluid: here, from some morbid action going on simultaneously in several parts of the cyst-wall; consequently, in them there was fouindI a fi<cure or slit; in this case, several rounded ulcers, rather resembling those so often seen in the stomach.All these cases, however, poinit to the same piractical conclusion; viz., the propriety of relieving the distension by operation in goodl time, before the pressutre of the fluid, or the irritation wlvieh it occasions, has led to ulceration, with all its attendant dangers.
Chronic Epstein-Barr Virus Infection Associated with Fever and Interstitial Pneumonitis
Authors: ROBERT T. SCHOOLEY
Journal: Annals of Internal Medicine (1986)

Two patients developed fever, interstitial pneumonitis, and pancytopenia associated with extremely high titers of antibody to replicative antigens of the Epstein-Barr virus. In contrast to most patients seropositive for Epstein-Barr virus, neither patient had an antibody response to the Epstein-Barr nuclear antigen K polypeptide. In addition, virus isolated from one patient had a deletion of the B95-8 type in the EcoRI C region of the genome. An etiologic relation between Epstein-Barr virus replication and the clinical manifestations of this syndrome is further shown by the response of each patient to acyclovir therapy. These patients have a new Epstein-Barr-virus-associated syndrome and provide additional evidence that acyclovir may play a role in therapy for selected patients with Epstein-Barr virus infection.
EXPLORATION AND TREATMENT OF FISSURES FROM SKULL FRACTURES.
Authors: H. H. A. BEACH
Journal: JAMA (1896)

The modern treatment of fractures of the skull, which includes the uncovering of all suspicious areas suggesting depression or the projection of bony spiculæ toward the dura, the removal of fragments and foreign matter of every description, the arrest of hemorrhage, adequate provision for drainage, faithful observance of asepsis both in operating and dressing, with such attention to the general condition of a patient as may be requisite, is, in a word, the impression that Lister and his teaching have made upon the surgical work of pre-antiseptic days. The results obtained before that time through the faithful and painstaking application of surgical principles, of which cleanliness as then understood was the corner-stone, are scarcely less astonishing than those of to-day, if just consideration is given the work prosecuted in ignorance of the existence of bacteria and their appalling ravages. The confidence and boldness with which the surgeon may now undertake
Volume and mortality in coronary artery bypass grafting
Authors: H. S Luft, J. D Parker
Journal: BMJ (1995)

Further reanalysis of existing trials is unlikely to yield new insights, which will require new studies.Anderson and Tomenson recommend investigation of antidepressants prescribed in clinical practice rather than in clinical trials.Such observational studies are subject to many potential biases, which reduce the validity of comparisons.'What is needed are large, well designed pragmatic randomised controlled trials in primary care settings; such trials will allow both reliable and generalisable estimation of the relative effectiveness and cost effectiveness of different classes of antidepressants, as used in routine clinical practice and over a longer period.Future randomised controlled trials comparing classes of antidepress- ants should also use more relevant outcomes to measure quality of life in those who continue to use treatments and those who drop out.
Severe peripheral neuropathy complicating legionnaires' disease.
Authors: D J Morgan, J Gawler
Journal: BMJ (1981)

ml).Her condition improved slowly, and she was discharged after three weeks.Four months after the initial episode, taking no medication, she was considered to be cured; laboratory results are shown in the table. Main laboratory data on admission and after full recoveryOn admission Four months later Serum Glucose (mmol 1) 4-6 5 0 Blood urea nitrogen (mmol 1) 5-0 5-7 Creatinine (,umol,l) 88 71 Uric acid (,umol 1) 125 262 Sodium (mmol(mEq)l) 141 143 Potassium (mmol(mEq) 1) 2-9 4 Chloride (mmol(mEq) 1) 112 101 Bicarbonate (mmol(mEq) 1) 3.7 2152 Arterial pH 7 12 7-38 Oxygen pressure (mm Hg) 111 88 Carbon dioxide pressure (mm Hg) 12 4 34 4 Calcium (mmol,l) 2 5 2-4 Phosphorus (mmol/l) 0 39 1 2 Magnesium (,umol, 1) 782 ND Ketones Negative ND Lactate (rsmol 1)
The Quality of Quality
Authors: Véronique L. Roger
Journal: Circulation (2014)

][3][4] Practice guidelines then incorporated the results of clinical trials, and, because guideline-based care processes were shown to be associated with outcomes, 5 performance measures became an indicator of the quality of care. 6Performance measures track whether or not evidence-based medications are administered after MI.However, they do not assess whether or not the dose is optimal.The dose is an important issue for statins, because their efficacy to prevent recurrent MI and death after the initial event has been shown to be greater at higher doses. 2,7 Article see p 1303The article by Arnold et al 8 in this issue of Circulation adds more depth to the conversation on quality of care after MI by examining the dose of statins that patients received after acute MI in an observational study.The authors report on data from the Translational Research Investigating Underlying disparities in acute Myocardial infarction Patients' Health status (TRIUMPH) study.TRIUMPH is an National Heart, Lung, and Blood Institute-funded prospective registry designed to study the outcomes after MI with a distinct focus on health status outcomes in black and white patients.TRIUMPH collected detailed data on the socioeconomic, clinical, treatment, health status, metabolic, and genetic characteristics of patients with acute MI enrolled in 24 centers across the United States between 2005 and 2008. 9The design of the TRIUMPH study included an extensive (5 hours) data collection process, and, on study completion, 4340 patients were eligible for analysis.The depth of the data collected in TRIUMPH provides an unprecedented opportunity to gain insights into critical aspects of the presentation, care, and outcome of patients with acute MI, and the report in the this issue of Circulation 8 illustrates such capabilities.The study describes statin initiation, and intensification and maximization of dose during MI hospitalization, as well, and reports both patient-level and hospital-level analyses.Statin initiation among previously
Alternating contractility in pulsus alternans studied in the isolated canine heart.
Authors: M D McGaughey, W L Maughan, K Sunagawa, K Sagawa
Journal: Circulation (1985)

We examined pulsus alternans in seven isolated, perfused canine left ventricles ejecting into a simulated arterial impedance. Left ventricular pressure-volume loops were measured during pulsus alternans while filing-source pressure was lowered. In all cases two distinct linear end-systolic pressure-volume relationships (ESPVRs) were noted for the strong and weak beats. The slopes of the ESPVRs of the strong beats were significantly greater than those of the weak beats (mean difference 0.9 +/- 0.6 mm Hg/ml, p less than .01), while the intercepts were not significantly different (mean difference 0.06 +/- 0.5 ml). Diastolic pressure-volume relationships for the strong and weak beats were not significantly different, excluding incomplete relaxation as a cause of pulsus alternans. Although the weak beats had both a smaller preceding end-diastolic volume and a larger end-systolic volume, the presence of two distinct ESPVRS for the strong and weak beats shows there is alternating ventricular chamber contractility in pulsus alternans that is not solely due to the Starling mechanism. The magnitude of alternation in pump function parameters such as pressure and stroke volume during pulsus alternans reflects the complex interactions of alternating contractile state with alternations in preload and afterload.
Pressure-guided nonsurgical myocardial reduction induced by small septal infarctions in hypertrophic obstructive cardiomyopathy
Authors: Peter Boekstegers, Peter Steinbigler, Alexander Molnar, Martin Schwaiblmair, Alexander Becker, Andreas Knez, Ralph Haberl, Gerhard Steinbeck
Journal: Journal of the American College of Cardiology (2001)
Preexisting Immunity and Low Expression in Primates Highlight Translational Challenges for Liver-directed AAV8-mediated Gene Therapy
Authors: Gregory D Hurlbut, Robin J Ziegler, Jennifer B Nietupski, Joseph W Foley, Lisa A Woodworth, Elizabeth Meyers, Scott D Bercury, Nilesh N Pande, David W Souza, Mark P Bree, Michael J Lukason, John Marshall, Seng H Cheng, Ronald K Scheule
Journal: Molecular Therapy (2010)

Liver-directed gene therapy with adeno-associated virus (AAV) vectors effectively treats mouse models of lysosomal storage diseases (LSDs). We asked whether these results were likely to translate to patients. To understand to what extent preexisting anti-AAV8 antibodies could impede AAV8-mediated liver transduction in primates, commonly preexposed to AAV, we quantified the effects of preexisting antibodies on liver transduction and subsequent transgene expression in mouse and nonhuman primate (NHP) models. Using the highest viral dose previously reported in a clinical trial, passive transfer of NHP sera containing relatively low anti-AAV8 titers into mice blocked liver transduction, which could be partially overcome by increasing vector dose tenfold. Based on this and a survey of anti-AAV8 titers in 112 humans, we predict that high-dose systemic gene therapy would successfully transduce liver in >50% of human patients. However, although high-dose AAV8 administration to mice and monkeys with equivalent anti-AAV8 titers led to comparable liver vector copy numbers, the resulting transgene expression in primates was ~1.5-logs lower than mice. This suggests vector fate differs in these species and that strategies focused solely on overcoming preexisting vector-specific antibodies may be insufficient to achieve clinically meaningful expression levels of LSD genes using a liver-directed gene therapy approach in patients.
Review: VTE prophylaxis in nonsurgical inpatients reduces PE but not death, and increases major bleeding
Authors: Andrew L. Freeman, Robert C. Pendleton
Journal: Annals of Internal Medicine (2012)

Source Citation Lederle FA, Zylla D, MacDonald R, Wilt TJ. Venous thromboembolism prophylaxis in hospitalized medical patients and those with stroke: a background review for an American College of Physicians clinical practice guideline. Ann Intern Med. 2011;155:602-15. 22041949
Abstract 3665: An EMT gene expression diagnostic predicts resistance to EGFR and MEK-targeted therapies in cell lines and patients
Authors: Sean F. Eddy, Paul Williams, Mark Tomilo, Seth Sadis, Peter Wyngaard, Lien Vo, Kahuku Oades, Hyunsoo Kim, Yipeng Wang, Byung-In Lee, Joseph Monforte, Daniel Rhodes
Journal: Cancer Research (2012)

Abstract The epithelial to mesenchymal transition (EMT) in cancer cells results in the acquisition of metastatic properties and may contribute to chemoresistance. Several studies have shown that transition to a mesenchymal phenotype leads to decreased dependence on EGFR-RAS signaling and insensitivity to EGFR inhibitors. To better understand the importance of EMT as a general predictor of drug response, we defined an EMT gene signature derived from a meta-analysis of differential gene expression signatures representing genes up-regulated following transfection of breast cell lines with various EMT regulators (Taube et al., 2010 Proc Natl Acad Sci USA 107:15449-54). We then determined the expression of the EMT signature across cell line panels and determined whether it predicted sensitivity or resistance to various targeted therapies. Consistent with previous results, expression of EMT signature was significantly associated with resistance to an EGFR inhibitor, lapatinib. Similarly, the EMT signature also predicted resistance to PQIP (IGF1R), GSK1120212 (MEK), GSK690693 (AKT), and perifosine (AKT/PI3K), suggesting that EMT may be a common resistance mechanism to a number of drugs that target growth factor signaling. As more of these targeted agents are entering clinical trials, the ability to characterize the signature may have important implications for drug development. To study the relevance of the EMT signature in clinical tumors, we compared the signature to a collection of tumor co-expression patterns, known as OncoScore modules, which were defined from 40,000+ tumor microarray experiments. Notably, the EMT signature was significantly associated with a major tumor co-expression pattern representing mesenchymal and/or stromal phenotype observed in almost all major solid tumor types. In retrospective microarray scoring analyses of key clinical datasets, the mesenchymal/stromal module predicted resistance to cetuximab. This finding was validated with an independent cohort of colorectal cancer patients treated with cetuximab using the Oncoscore Colon diagnostic. Oncoscore Colon is a qPCR test optimized for formalin-fixed paraffin-embedded tissue that measures the twelve key colon cancer transcriptional modules, including the mesenchymal module. Because the mesenchymal/stromal module monitors a fundamental phenotype of cancer cells important for drug response, this validated qPCR test has broad application to companion diagnostics development and personalized medicine. 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 3665. doi:1538-7445.AM2012-3665
Mussel‐Inspired Coating of Polydopamine Directs Endothelial and Smooth Muscle Cell Fate for Re‐endothelialization of Vascular Devices
Authors: Zhilu Yang, Qiufen Tu, Ying Zhu, Rifang Luo, Xin Li, Yichu Xie, Manfred F. Maitz, Jin Wang, Nan Huang
Journal: Advanced Healthcare Materials (2012)

Polydopamine (PDAM), a mussel adhesive protein inspired coating that can be easily deposited onto a wide range of metallic, inorganic, and organic materials, gains interest also in the field of biomaterials. In this work, PDAM is applied as coating on 316L stainless steel (SS) stents and the response of cells of the blood vessel wall, human umbilical vein endothelial cell (HUVEC), and human umbilical artery smooth muscle cell (HUASMC) as predictors for re-endothelialization is tested. It is found that the PDAM-modified surface significantly enhances HUVEC adhesion, proliferation, and migration, release of nitric oxide (NO), and secretion of prostaglandin I(2) (PGI(2) ). Additionally, the PDAM-modified surface shows a remarkable ability to decrease the adhesion and proliferation of HUASMCs. As a blood-contacting material, the PDAM tends to improve the hemocompatibility compared with the substrate 316L SS. It is noteworthy that the PDAM coating shows good resistance to the deformation behavior of compression and expansion of a stent. These data suggest the potential of PDAM as a blood-contacting material for the application in vascular stents or grafts.