tbuckley/cabot-search huggingface dataset:
Single determination of C-reactive protein at the time of diagnosis predicts long-term outcome of patients with hepatocellular carcinoma
Authors: Wolfgang Sieghart, Matthias Pinter, Florian Hucke, Ivo Graziadei, Maximilian Schöniger-Hekele, Christian Müller, Wolfgang Vogel, Michael Trauner, Markus Peck-Radosavljevic
Journal: Hepatology (2012)

Abstract We investigated the prognostic value of C-reactive protein (CRP) in patients with hepatocellular carcinoma (HCC) not amenable to surgery. A total of 615 patients diagnosed with HCC not amenable to surgery between April 1999 and December 2009 at the Department of Gastroenterology of the Medical Universities of Vienna and Innsbruck were included. We assessed the optimal CRP cutoff by regression spline analysis and tested its impact on median overall survival (OS) by the Kaplan-Meier method, univariate analysis (log-rank test), and multivariate analysis (Cox proportional hazard regression model) in a training cohort (n = 466, Vienna) and an independent validation cohort (n = 149, Innsbruck). We found a sigmoid-shaped association of CRP and the hazard ratio of death upon regression spline analysis and defined a CRP level &lt;1/≥1 mg/dL as optimal cutoff for further survival assessments. Elevated CRP (≥1 mg/dL) at diagnosis was associated with poor OS (CRP-elevated versus CRP-normal; 4 versus 20 months; P &lt; 0.001) and remained a significant negative predictor for OS upon multivariate analysis (hazard ratio, 1.7; P &lt; 0.001), which was independent of age, Child-Pugh class, tumor characteristics, and treatment allocation. Analyses with respect to Barcelona Clinic Liver Cancer (BCLC) stage and Child-Pugh class supported the relevance of CRP (BCLC-stage C and Child-Pugh A: OS for CRP-elevated versus CRP-normal, 6 versus 14; P &lt; 0.001; BCLC-stage C and Child-Pugh B: OS for CRP-elevated versus CRP-normal, 4 versus 15 months; P &lt; 0.001). The prognostic significance of elevated CRP was reproducible at a second CRP determination timepoint and confirmed in the independent validation cohort. Conclusion: Elevated CRP is associated with a dismal prognosis in HCC patients and may become a useful marker for patient selection in HCC management.
Autopsy pathology; a guide for pathologists and clinicians
Authors: S. L. Wilens
Journal: JAMA (1963)

There was once a choleric pathologist who classified textbooks according to whether they were best employed as head rests, section boards, or as peritoneal refill. Fellow pathologists, however, will feel strongly sympathetic towards Rezek and Millard's book which espouses the cause of better autopsies so ardently and convincingly. The authors are indeed excellent pathologists of wide experience. What is more, their enthusiasm for their specialty shines clearly forth on almost every page. Someone else's textbook is said to be the textbook writer's best friend. This book, however, has an original rather than a replicated aura. Many pathologists have toyed with the idea of spawning a manual on autopsy technique, largely because they are proud and jealous of their own skill and regard all deviationists as heretical. The techniques expounded in the present book have become standard practice, if they are not always in the William Welch tradition. The size and
AMMONIUM TOLERANCE IN LIVER DISEASE: OBSERVATIONS BASED ON CATHETERIZATION OF THE HEPATIC VEINS
Authors: Laurens P. White, Elizabeth A. Phear, W. H. J. Summerskill, Sheila Sherlock, Marjorie Cole
Journal: Journal of Clinical Investigation (1955)

The concept that substances from intestinal con- tents, passing into the general circulation, may cause toxic symptoms has been of particular in- terest in the study of liver disease.In 1896, Nencki, Pawlow, and Zaleski (1) demonstrated that diversion of portal blood, containing large amounts of ammonium, into the general circulation by an Eck fistula resulted in an increase in am- monium content of peripheral blood.In cirrhosis of the liver and in patients with porta-caval anasto- moses elevation of blood ammonium has frequently been found and in some cases correlated with neurological disturbances (2-10).The reason for the elevation of blood ammonium in these cases has not been determined precisely.Van Caulaert, Deviller, and Halff (3, 10) sug- gested that in cirrhosis this abnormality of am- monium was related to the presence of portal col- lateral veins with shunting of portal blood di- rectly into the systemic circulation.Kirk (2) supported this hypothesis with extensive studies.To evaluate the roles of portal collateral circu- lation and of liver function in the control of blood ammonium levels, simultaneous sampling from antecubital and hepatic veins has been undertaken.To accentuate differences in ammonium content at these sites, and to test patients' ability to metabo- lize ammonium, a standard dose of ammonium chloride has been given by mouth.The results of such investigations, with corollary observations, form the basis of this report.
"TRAUMATIC GASTRIC ULCERS."
Authors: T. R. Elliott, H. Henry
Journal: BMJ (1916)

SuP.GICAL WOrk kwith the army in France during the last -six -months-has-proved conclusivelv the value of early operation in gunshot wounds of thle abdomen.-In his admirable summary' of the experience gained by the careful observations of several workers in one army area, Colonel Cuthbert Wallace states the clear rile that a perforating wound of the intestine cannot be healed by spontaneous closure, and tlhat suchl injuries of necessity rmiust be treated by operative procedures at as early a moment as is possible.With regard to vwounds of the stomachl there is still doubt, because there are some grounds for the belief that such lesions are capable of cure by natural processes, and because it is certain that the wounds will often be found to lie in areas which are difficult for the surgeon to reach.
Decrease in Peripheral Sympathetic Nervous System Activity following Renal Denervation or Unclipping in the One-Kidney One-Clip Goldblatt Hypertensive Rat
Authors: Richard E. Katholi, Sherry R. Winternitz, Suzanne Oparil
Journal: Journal of Clinical Investigation (1982)

Increased sympathetic nervous system activity has been demonstrated in established one-kidney one-clip hypertension in the rat. We have found that renal denervation in this model results in an attenuation of hypertension, unassociated with alterations in sodium or water balance or renin activity. To determine whether the depressor effect of renal denervation is associated with changes in peripheral sympathetic nervous system activity, sham operation (n = 12), renal denervation (n = 13), or unclipping (n = 13) was carried out 2 wk after the onset of one-kidney one-clip hypertension. Normotensive unine-phrectomized age- and sex-matched rats were used as controls (n = 14). Renal denervation resulted in a significant decrease in systolic blood pressure (201±7 to 151±6 mm Hg), while unclipping lowered systolic blood pressure to normotensive levels (130±6 mm Hg). 8 d after operation plasma norepinephrine and mean arterial pressure before and after ganglionic blockade with 30 mg/kg hexamethonium bromide were measured in conscious, unrestrained, resting animals, as indices of peripheral sympathetic nervous system activity. Plasma norepinephrine was significantly higher in hypertensive sham-operated rats (422±42 pg/ml) compared with normotensive controls (282±25 pg/ml) (P < 0.01). Both renal denervation and unclipping restored plasma norepinephrine to normal levels (273±22 and 294±24 pg/ml, respectively). Ganglionic blockade in hypertensive sham-operated animals resulted in a significantly greater decrease in mean arterial pressure than occurred in renal denervated, unclipped, or control rats. The data suggest that the depressor effect of renal denervation or unclipping in the one-kidney one-clip hypertensive rat is associated with a decrease in peripheral sympathetic nervous system activity.
Impaired Parathyroid Hormone Metabolism in Patients with Chronic Renal Failure
Authors: Jeffrey Freitag, Kevin J. Martin, Keith A. Hruska, Charles Anderson, Mollie Conrades, Jack Ladenson, Saulo Klahr, Eduardo Slatopolsky
Journal: New England Journal of Medicine (1978)

SECONDARY hyperparathyroidism, with markedly elevated levels of circulating parathyroid hormone, is a universal complication of chronic renal failure.1 , 2 Increased secretion has been accepted as the underlying mechanism responsible for the high levels of parathyroid hormone seen in uremic subjects. Multiple factors have been implicated in the pathogenesis of parathyroid hormone hypersecretion in chronic renal disease, including phosphate retention,3 impaired production of 1,25-dihydroxycholecalciferol4 leading to impaired intestinal calcium absorption,5 , 6 and skeletal resistance to the action of parathyroid hormone.7 , 8 In recent years, the importance of the kidney in the metabolism of parathyroid hormone has been recognized. Berson and Yalow9 demonstrated a prolonged . . .
Left ventricular outflow tract obstruction produced by redundant mitral valve tissue in a neonate. Clinical, angiographic, and operative findings.
Authors: J W Mathewson, T A Riemenschneider, E C McGough, V R Condon
Journal: Circulation (1976)

An unusual case of left ventricular outflow tract obstruction associated with severe left ventricular failure in a neonate is reported. The physical and laboratory data were consistent with the diagnosis of infantile valvular aortic stenosis. At operation, however, redundant gelatinous pedunculated tissue attached to the mitral valve annulus appeared to move through and obstruct the aortic valve during systole. The aortic valve showed only minimal thickening of the right and left coronary cusps. A distinct angiographic pattern was demonstrated during left ventricular cineangiography. In the frontal projection a large ovoid filling defect appeared to protrude through the aortic valve during systole and return to a subvalvular location during diastole. Recognition of this angiographic pattern should facilitate diagnosis and subsequent repair. Complete correction is possible by operative excision of the obstructing tissue without damaging the mitral valve. In contrast to isolated congenital infantile valvular aortic stenosis, a condition in which the valve leaflets are often primitive and deformed, aortic valvotomy and/or subsequent valve replacement are not necessary, resulting in a better long-term prognosis.
Case 37-1978
Authors: Gordon L. Snider, Karl H. Proppe
Journal: New England Journal of Medicine (1978)

Presentation of CaseA 42-year-old man was admitted to the hospital because of pulmonary infiltrates.He was well until two months previously, when a tender swelling developed abruptly in the left side of the neck. It grew rapidly and was incised and drained. Microscopical examination of the excised material revealed an inflamed branchial-cleft cyst. A culture yielded no growth of micro-organisms. An x-ray film of the chest showed a nodular patchy consolidation in the peripheral portion of the right-lower-lung field. A tuberculin skin test was reported to be negative. Penicillin was given for two weeks. One month before admission another . . .
Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production
Authors: Gary D Wu, Charlene Compher, Eric Z Chen, Sarah A Smith, Rachana D Shah, Kyle Bittinger, Christel Chehoud, Lindsey G Albenberg, Lisa Nessel, Erin Gilroy, Julie Star, Aalim M Weljie, Harry J Flint, David C Metz, Michael J Bennett, Hongzhe Li, Frederic D Bushman, James D Lewis
Journal: Gut (2014)

<h3>Objective</h3> The consumption of an agrarian diet is associated with a reduced risk for many diseases associated with a 'Westernised' lifestyle. Studies suggest that diet affects the gut microbiota, which subsequently influences the metabolome, thereby connecting diet, microbiota and health. However, the degree to which diet influences the composition of the gut microbiota is controversial. Murine models and studies comparing the gut microbiota in humans residing in agrarian versus Western societies suggest that the influence is large. To separate global environmental influences from dietary influences, we characterised the gut microbiota and the host metabolome of individuals consuming an agrarian diet in Western society. <h3>Design and results</h3> Using 16S rRNA-tagged sequencing as well as plasma and urinary metabolomic platforms, we compared measures of dietary intake, gut microbiota composition and the plasma metabolome between healthy human vegans and omnivores, sampled in an urban USA environment. Plasma metabolome of vegans differed markedly from omnivores but the gut microbiota was surprisingly similar. Unlike prior studies of individuals living in agrarian societies, higher consumption of fermentable substrate in vegans was not associated with higher levels of faecal short chain fatty acids, a finding confirmed in a 10-day controlled feeding experiment. Similarly, the proportion of vegans capable of producing equol, a soy-based gut microbiota metabolite, was less than that was reported in Asian societies despite the high consumption of soy-based products. <h3>Conclusions</h3> Evidently, residence in globally distinct societies helps determine the composition of the gut microbiota that, in turn, influences the production of diet-dependent gut microbial metabolites.
PROGNOSIS IN THE HEART DISEASES OF CHILDREN.
Authors: ARTHUR V. MEIGS
Journal: JAMA (1900)

I have examined several text-books on the diseases of children, and in all of them I found that the discussion of prognosis occupied but very little space. It would not take me ten minutes to read to you all that I found in two or three text-books, and it will not be necessary, therefore, for me to occupy very much time in discussing the subject. It has impressed me, as it must have impressed every physician who has had the opportunity to see sick children, that when they suffer from disease of the heart the prognosis should generally be more hopeful than when adults suffer with heart disease. This is partly because they are more elastic than adults, whose tissues are stiffer and may almost be said to be brittle, and most of all, perhaps, because children who have not attained their full growth have the opportunity for repair during
Abstract A47: Microfluidic in vitro platform for imaging metastasis: Perfusable microvascular networks and cancer cells on a microfluidic chip
Authors: Noo Li Jeon, Sudong Kim, Lee Hyunjae, Chung Minhwan
Journal: Cancer Research (2013)

Abstract In vivo imaging has provided significant insights to different mechanisms involved in cancer metastasis. An in vitro experimental platform that reproduce cancer microenvironment with blood vessels, tumors, immune cells and others would allow more detailed experiments with more experimental conditions can complement the animal studies. We describe a reproducible, in vitro approach to grow perfusable 3D microvascular networks on a microfluidic chip. These engineered blood vessels exhibit morphological and biochemical markers of tight junctions, apical-basal polarity, basement membrane deposition, and upregulated markers in response to inflammatory cues. A novel microfluidic device was designed and tested for real-time imaging of various steps of cancer metastasis. Perfusable microvascular networks formed within the microfluidic device reproduce the 3D cellular niche, facilitating high-resolution live imaging of cancer cell extravasation. This approach provides a platform for developing physiologically complex but experimentally straightforward human disease models and holds potential for medical and pharmaceutical applications in drug screening and basic cancer biology. Citation Format: Noo Li Jeon, Sudong Kim, Lee Hyunjae, Chung Minhwan. Microfluidic in vitro platform for imaging metastasis: Perfusable microvascular networks and cancer cells on a microfluidic chip. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A47.
Dog Bites-Reply
Authors: Trudy A. Karlson
Journal: JAMA (1985)

<h3>In Reply.—</h3> In my study, I reported the relatively high incidence rates of hospital-treated facial injuries from dog bites in Dane County, Wisconsin: 152 per 100,000 for children aged 0 to 4 years, and for children aged 0 to 14 years, a cumulative incidence of 1.5%. For children aged 0 to 9 years, the proportion of severe bites was 19%. Even if this proportion is considered to be small by Dr Booker, dog bites were the most common cause of severe facial laceration in children in Dane County. Nationally, these rates yield 44,000 facial bites sustained by children each year, 16,000 of them severe. This is a significant public health problem. Bites seem to occur as a result of dog and human interactions most of us would call "normal"<sup>1</sup>—the "provoked incidents" in Parrish's article to which Dr Booker refers include feeding, picking up, and holding dogs.<sup>2</sup>An additional
Acetaminophen-Induced hepatotoxic congestion in mice
Authors: Robin M. Walker, William J. Racz, Francis T. McElligott
Journal: Hepatology (1985)

Acetaminophen–induced (750 mg per kg p.o.) hepatotoxicity in mice is characterized by hepatomegaly and massive centrilobular congestion which precede the appearance of necrosis. The vascular changes are correlated with the morphologic features using liver hemoglobin content to quantitate erythrocyte sequestration, and hematocrit measurements and 125 I–albumin injections to determine plasma and blood volume. The initial increase in liver size was a result of plasma accumulation due to endocytic vacuolation of hepatocytes and Disse space enlargement in centrilobular regions. Further increases in liver size after 3 hr were a consequence of erythrocyte and additional plasma sequestration within the damaged liver. These events occurred without any increase in intrahepatic or portal venous pressure. Hepatic hemoglobin and plasma levels increased 10– and 5–fold, respectively, by 4.5 to 6 hr after administration of acetaminophen. There are two major consequences of acetaminophen–induced hepatotoxic congestion. First, blood and plasma volumes fell significantly, and we suggest that hypovolemic shock contributes to early mortality after acetaminophen. Second, impaired circulation within the congested liver, as manifested by reduced 125 I–albumin entry into the liver when 125 I–albumin was injected after congestion had developed, probably aggravates the initial injury. Early lesions were always evenly distributed around central veins. However, the pattern of damage at 24 hr could be variable. Occasional large confluent areas of necrosis were always congested, which is consistent with the concept that secondary ischemic damage can develop. Congestion and hypovolemia are reversible and can be largely prevented by administration of the protective compound N –acetylcysteine (1,200 mg per kg p.o.) 3 hr after acetaminophen.
Abstract A20: IDH mutations and 2-HG selectively affect histone methylation in the endogenous setting
Authors: Fallon Lin, Veronica Saenz-Vash, Huili Zhai, Joy Fletcher, Mike Acker, David Jiang, John Gounarides, Julian Levell, Raymond Pagliarini
Journal: Cancer Research (2013)

Abstract Highly recurrent somatic mutations in the isocitrate dehydrogenase (IDH) 1 and 2 enzymes have been identified in a variety of tumor types including GBM and glioma subtypes, acute myelogenous leukemia, chondrosarcoma, and cholangiocarcinoma, among others. Mutant IDH proteins gain a novel function: the production of the “oncometabolite” 2-hydroxyglutarate (2-HG), which accumulates in the tumors of affected patients. The similarity of 2-HG to a-ketoglutarate, a cofactor required for the function of a large number of cellular enzymes, has led to the hypothesis that 2-HG may alter the function of one or more of these enzymes. Current literature has shown that 2-HG is able to inhibit a number of epigenetic factors (i.e. Jmj-domain histone demethylases, and the TET family of methylcytosine oxidases) though most of these studies have been carried out using over-expression systems that can potentially force non-relevant phenotypes. To this end, we explored histone methylation changes in a variety of cells that harbor endogenous heterozygous IDH1/2 mutations. Using an LC-MS based method to detect histone modifications, we profiled IDH MUT vs. WT cells to evaluate which global histone methylation changes correlated with mutant IDH status and whether these changes were widespread or discrete. This unbiased search highlighted IDH-dependent modifications of Histone 3 on Lysine 9 (H3K9) as the histone mark of highest interest for further study. We followed up by assessing the sufficiency and necessity of IDH mutation and 2-HG to alter H3K9 methylation using immunoblotting techniques. Our results suggest that H3K9 methylation is particularly sensitive to mutant IDH and 2-HG, which may give us further insight into the mechanism of how mutant IDH drives tumorgenicity. Citation Format: Fallon Lin, Veronica Saenz-Vash, Huili Zhai, Joy Fletcher, Mike Acker, David Jiang, John Gounarides, Julian Levell, Raymond Pagliarini. IDH mutations and 2-HG selectively affect histone methylation in the endogenous setting. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr A20.
Abstract LB-45: VEGFR3 signaling facilitates mammary tumor cells to resist chemotherapy
Authors: Bhawna Sharma, Michelle L. Varney, Rakesh K. Singh
Journal: Cancer Research (2014)

Abstract Breast cancer is a deadly disease which accounts for more than 40,000 deaths each year in United States. With the availability of various treatment options, side effects and resistance associated with them is also becoming a major concern for the treatment of breast cancer. How breast cancer cells evade chemotherapy still remains a vast area for research. In this study, we proposed that mammary tumor cells resist cell death via VEGFR3 signaling pathway. To test our hypothesis, we used doxorubicin and paclitaxel resistant murine mammary tumor cells (Cl66-Dox and Cl66-Pac) which have been developed in our laboratory. When implanted in female Balb/c mice they form more aggressive tumor than the parent cells (Cl66) from which they have been derived. We observed that these resistant cells have higher expression of VEGFR3 receptor than parent cells at mRNA level. Treatment with VEGFR3 kinase inhibitor, MAZ51, Cl-66Dox and Cl66-Pac cells showed 50% growth inhibition at 10uM dose, suggesting VEGFR3 receptor activation as one of the mechanism for resistance. Moreover, when implanted in mice, tumor formed by resistant cells responded well to MAZ51 treatment with slower tumor growth in comparison to control group consistent with our in vitro data. However, when we treated mice bearing resistant tumors first with chemotherapeutic drug, docetaxel followed by MAZ51, we observed a significant decrease in tumor growth and tumor weight, examined upon endpoint analysis. These results suggest that combination treatment is more effective in inhibiting drug-resistant tumors growth in comparison to drug and inhibitor alone as determined by reduced tumor volume and weight in combination treatment group. Overall, our in vivo data showed that blocking VEGFR3 signaling pathway makes drug-resistant mammary tumor cells susceptible to chemotherapy suggesting the use of inhibitors for this signaling pathway to be beneficial for drug-resistant mammary tumors. Citation Format: Bhawna Sharma, Michelle L. Varney, Rakesh K. Singh. VEGFR3 signaling facilitates mammary tumor cells to resist chemotherapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-45. doi:10.1158/1538-7445.AM2014-LB-45