tbuckley/cabot-search huggingface dataset:
Drug users should be able to get heroin from the health system
Authors: M. T. Schechter
Journal: BMJ (2015)

Politicians may not like it, but evidence shows that giving heroin to some users reduces harm, argues Martin T Schechter 

At first glance, the idea of heroin assisted treatment may seem preposterous. Rona Ambrose, Canada’s health minister, certainly thinks so. When physicians in Vancouver continued to prescribe heroin on compassionate grounds to a small number of patients who had benefited from it in a clinical trial, essentially implementing the first heroin prescription programme in North America, the minister changed some regulations to try to end the practice.

“The prime minister and I do not believe we are serving the best interests of those addicted to drugs and those who need our help the most”—said Ambrose in October 2013—“by giving them the very drugs they are addicted to.” Similarly, John Walters, the US drug czar under President George W Bush, called such harm reduction activities “state assisted suicide.”

However, before responding with a similar knee jerk reaction, pause to consider an especially vulnerable subgroup of people with heroin addiction. I refer to those with longstanding illness for whom our best available treatments, such as detoxification, abstinence programmes, and methadone maintenance, have …
Treatment of fibrolamellar hepatoma with subtotal hepatectomy or transplantation
Authors: A D Pinna, S Iwatsuki, R G Lee, S Todo, J R Madariaga, J W Marsh, A Casavilla, I Dvorchik, J J Fung, T E Starzl
Journal: Hepatology (1997)

Fibrolamellar hepatoma (FL-HCC) is an uncommon variant of hepatocellular carcinoma (HCC), distinguished by histopathological features suggesting greater differentiation than conventional HCC. However, the optimal treatment and the prognosis of FL-HCC have been controversial. Follow-up studies are available from 1 year to 27 years, after 41 patients with FL-HCC were treated with partial hepatectomy (PHx) (28 patients) or liver transplantation (13 patients). In this retrospective study, the effect on outcome was determined for the pTNM stage and other prognostic factors routinely recorded at the time of surgery. Cumulative survival at 1, 3, 5, and 10 years was 97.6%, 72.3%, 66.2%, and 47.4%. Tumor-free survival at these times was 80.3%, 49.4%, 33%, and 29.3%. The TNM stage was significantly associated with tumor-free survival. Patients with positive nodes had a shorter tumor-free survival than those with negative nodes (P < .015). Patient survival was most adversely affected by the presence of vascular invasion (P < .05). FL-HCC is an indolently growing tumor of the liver, which usually was diagnosed in our patients at a stage too advanced for effective surgical treatment of most conventional HCC. Nevertheless, long-term survival frequently was achieved with aggressive surgical treatment. When a subtotal hepatectomy could not be performed, total hepatectomy (THx) with liver transplantation was a valuable option.
Aorto-jejunal fistula from rupture of Teflon graft, with septic emboli in the skin.
Authors: A. Martin, P. W. Copeman
Journal: BMJ (1967)

Contamination of Disinfectants-Burdon and Whitby MICJOURNAL 155 hospitals.In all these hospitals organisms similar to those here reported were found; 30 out of the 48 samples taken yielded a growth of Pseudomonas sp.In one pharmacy the distilled TABLE III.-Organisms Isolated from Different Batches of 1 in 30 Savlon Batch
The Diarrhea of Travelers
Authors: B. H. Kean, Somerset R. Waters
Journal: New England Journal of Medicine (1959)

ACUTE diarrhea is well known to travelers recently arrived in Italy, Turkey, Egypt, India, Mexico and many other countries, where picturesque names have been applied to the syndrome — for example, "Delhi belly," the "Turkey trot," "Gippy tummy," "Montezuma's revenge" and the "G.I.'s." The diarrhea varies in degree from a mild transformation of formed stools to a semisolid or liquid state, to an explosive illness characterized by nausea, vomiting, fever, severe diarrhea, with dehydration, depletion and even death in the debilitated.§ Whether the syndrome is due to one agent or is a complex of many different diseases is not known. . . .
Inhibition of Invasion and Metastasis of Hepatocellular Carcinoma Cells via Targeting RhoC <i>In vitro</i> and <i>In vivo</i>
Authors: Wei Wang, Fan Wu, Feng Fang, Yiming Tao, Lianyue Yang
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Hepatocellular carcinoma (HCC) is one of the most deadly human cancers because of its high incidence of metastasis. Our previous work identified a strong correlation between increased expression of RhoC and HCC metastasis. Here, we investigate to define the role of RhoC in HCC metastasis. Furthermore, we sought to determine whether inhibition of the expression of RhoC might block the metastasis of HCC in vivo. Experimental Design: A stable retroviral small interfering RNA approach was employed to selectively knockdown the expression of RhoC in vitro and in vivo. Invasion and migration assay, MTT and fluorescence-activated cell sorting analysis, Rho activity assay, and immunofluorescence staining were carried out to characterize RhoC in vitro. An anti-RhoC retroviral gene delivery BALB/c nude mice model was established to investigate whether knockdown of the expression of RhoC might inhibit the metastasis of HCC in vivo. Results: We confirmed the correlation of RhoC expression and metastatic potentials of HCC cell lines. We also showed that suppression of RhoC expression resulted in inhibition of invasion and migration without an apparent effect on cell survival and proliferation in HCCLM3 cells. Furthermore, a similar effect of RhoC on autotaxin-induced invasion of HCCLM3 cells was also observed. Significantly, we successfully adopted an HCC metastatic mouse model that allowed us to show that knockdown of the RhoC expression resulted in inhibition of metastasis of HCC in vivo for the first time. Conclusions: Our results show a critical role of RhoC in metastasis of HCC, implicating RhoC as a potential therapeutic target to block HCC metastasis.
Evaluation of Left Ventricular Performance
Authors: GEORGE BENZING, JAMES STOCKERT, EDWIN NAVE, SAMUEL KAPLAN
Journal: Circulation (1974)

In the first part of the study, the influence of changes in preload and afterload on mean circumferential fiber shortening velocity, Vcf, was investigated in the absence of any extrinsic cause for change in the contractile state of the left ventricle (LV) of seven dogs. In five of seven dogs in which afterload was controlled and contractility was unchanged, there was a significant negative correlation between LV end-diastolic pressure and mean Vcf expressed in circumferences per second ( r = –.88 to –.97). In one dog there was a positive correlation ( r = +0.847) and in another dog there was no significant correlation. Correlation as a group was poor. In five of the above seven dogs in which afterload was decreased from a control level while preload was controlled and contractility was not extrinsically altered, mean Vcf increased in all instances. Because of the influence of afterload on Vcf increased in all instances. Because of the influence of afterload on Vcf and the inconsistent relation between Vcf and preload, we controlled preload and afterload during assessment of Vcf in reflecting a change of LV contractility. Since mean left ventricular hydraulic output power, MLVP, quantitates practically all of the mechanical power of the left ventricular musculature, MLVP was utilized to represent the contractile state of the left ventricle under conditions in which preload and afterload were controlled. Mean and peak Vcf, Vcf at peak tension, extent of circumferential fiber shortening, and peak tension were compared with MLVP to test their usefulness in reflecting a change in the contractile state of the LV. Twenty dogs were divided into four groups of five each. Group I was exposed to cardiopulmonary bypass alone. Dogs of groups II, III, and IV were exposed to a total of 45 minutes of myocardial ischemia during bypass. After bypass, groups I, II, III and IV retained an average of 89.3, 79.9, 82.5 and 69.2% of the control or original mean Vcf, and 87.1, 63.9, 53.4 and 33.5% of the control MLVP, respectively. Although an effect of ischemia was detected by changes of peak tension and extent of fiber shortening, the statistical evidence was less satisfactory than observed for MLVP. It was concluded that mean Vcf, peak Vcf, and Vcf at peak tension are inadequate indices to detect acute changes in the contractile state of the LV produced by prior myocardial ischemia. These same changes in contractility are readily determined by MLVP.
Association of Genetic Polymorphisms in the <i>VEGF</i> Gene with Breast Cancer Survival
Authors: Hua Lu, Xiao-Ou Shu, Yong Cui, Nobuhiko Kataoka, Wanqing Wen, Qiuyin Cai, Zhi-Xian Ruan, Yu-Tang Gao, Wei Zheng
Journal: Cancer Research (2005)

Abstract The vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and vascular permeability. VEGF overexpression has been associated with advanced stage and poor survival of several cancers. We evaluated the association of functional polymorphisms in the VEGF gene with breast cancer survival in a cohort of 1,193 breast cancer patients who were recruited as part of a population-based case-control study in Shanghai, China from 1996 to 1998 and followed for cancer recurrence and mortality between March 2000 and December 2002. Included in the study were three functional polymorphisms (C−460T, G+405C, and C+936T) in the VEGF gene. Carrying the −460C or +405G allele was associated with decreased overall survival. The age-adjusted hazard ratios (HR) were 1.5 [95% confidence interval (95% CI), 0.9-2.5] for −460CC genotype carriers and 1.6 (95% CI, 1.0-2.5) for +405GG genotype carriers compared with noncarriers. Further analyses showed that the −460T/+450C/+936C haplotype was related to increased survival (HR, 0.57; 95% CI, 0.4-0.9), whereas the −460C/+405G/+936T haplotype was associated with nonsignificantly decreased survival (HR, 2.1; 95% CI, −0.9 to 4.7). The C+936T polymorphism alone was not related to overall or disease-free survival. This study suggests that VEGF polymorphisms may be a significant genetic marker for breast cancer prognosis.
Advances in Inflammatory Bowel Diseases (Falk Symposium 106)
Authors: F SHANAHAN
Journal: Gut (2001)

It has been a matter of debate whether gastric acid hypersecretion observed in patients with DU is a result of H pylori infection or if the infection accelerates development of DU in subjects who originally had acid hypersecretion.Our data showing that acid secretion was recovered in association with the decrease in serum gastrin levels in some DU patients and that MAO levels in patients with DU after eradication are still higher than those of normal subjects without H pylori infection may support the latter idea.Moreover, this idea may explain the fact that there are more patients with GU than DU among Japanese subjects, 9 who exhibit lower acid secretion than Western patients.
Fibrinolytic System During Long-Distance Running in IDDM Patients and in Healthy Subjects
Authors: Bert-Jan Potter van Loon, Leo P Heere, Cornelius Kluft, Ernest Briët, Gerard Dooijewaard, Arend E Meinders
Journal: Diabetes Care (1992)

OBJECTIVE Endurance exercise has been advocated in diabetes mellitus to improve both metabolic control and prevent atherosclerotic complications. The response of the fibrinolytic system during prolonged exercise has not been studied in diabetes. RESEARCH DESIGN AND METHODS In seven male marathon runners with IDDM and eight healthy nondiabetic male control subjects, matched for age and degree of training, we studied fibrinolytic and coagulation parameters during a 3-h 32-km outdoor running session. Measurements included t-PA, u-PA, PAI-1, PAP (as a measure of in vivo activation of fibrinolysis), FbDPs, FGN, vWF, and VIII:C. RESULTS In both IDDM and control subjects, levels of t-PA, u-PA, PAP, vWF, and VIII:C continued to rise throughout the exercise, whereas PAI-1 showed a similar decline in both groups. FbDP rose slightly in both groups, and FGN remained unchanged. t-PA levels during exercise correlated closely with exercise intensity. These findings indicate that continued stimulation by exercise does not deplete endothelial PA stores. Differences between IDDM and control subjects were seen only for t-PA, vWF, and u-PA. The AUC during exercise (AUC0.5−3.0) of t-PA in IDDM was insignificantly lower than in control subjects (53 ± 19 vs. 67 ± 31 ng.ml−1.h), but the ratio of t-PA to exercise intensity was lower in IDDM (0.24 ± 0.11 vs. 0.31 ± 0.13, P &amp;lt; 0.05). The AUC0.5−3.0 of vWF was lower in IDDM than in control subjects (569 ± 268 vs. 880 ± 265%·h, P &amp;lt; 0.05). The AUC0.5−3.0 of u-PA was higher in IDDM than in control subjects (15.1 ± 3.5 vs. 11.2 ± 1.8 ng.ml−1.h, P &amp;lt; 0.05). CONCLUSIONS Despite a defect in the exercise-induced endothelial release of vWF and t-PA, the overall potential to activate fibrinolysis is intact in IDDM, possibly by enhancement of u-PA after exercise. Our data suggest that in IDDM, as in nondiabetic subjects, long-distance running may slow the progression of atherosclerosis by stimulating fibrinolysis.
Court hears how drug giant Merck tried to "neutralise" and "discredit" doctors critical of Vioxx
Authors: R. Moynihan
Journal: BMJ (2009)

<h3>Objective.</h3> To describe the prevalence and clinical correlates of endoscopic gastric antral vascular ectasia (GAVE; “watermelon stomach”) in early diffuse systemic sclerosis (SSc). <h3>Methods.</h3> Subjects with early, diffuse SSc and evidence of specific internal organ involvement were considered for the Scleroderma: Cyclophosphamide Or Transplant (SCOT) trial. In the screening procedures, all patients underwent upper gastrointestinal endoscopy. Patients were then categorized into those with or without endoscopic evidence of GAVE. Demographic data, clinical disease characteristics, and autoantibody data were compared using Pearson chi-square or Student t tests. <h3>Results.</h3> Twenty-three of 103 (22.3%) individuals were found to have GAVE on endoscopy. Although not statistically significant, anti-topoisomerase I (anti-Scl70) was detected less frequently among those with GAVE (18.8% vs 44.7%; p = 0.071). Similarly, anti-RNP antibodies (anti-U1 RNP) showed a trend to a negative association with GAVE (0 vs 18.4%; p = 0.066). There was no association between anti-RNA polymerase III and GAVE. Patients with GAVE had significantly more erythema or vascular ectasias in other parts of the stomach (26.1% vs 5.0%; p = 0.003). <h3>Conclusion.</h3> Endoscopic GAVE was present on screening in almost one-fourth of these highly selected patients with early and severe diffuse SSc. While anti-Scl70 and anti-U1 RNP trended toward a negative association with GAVE, there was no correlation between anti-RNA Pol III and GAVE. Patients with GAVE had a higher frequency of other gastric vascular ectasias outside the antrum, suggesting that GAVE may represent part of the spectrum of the vasculopathy in SSc.
Abstract 4566: AGS-1C4D4: A fully human anti-PSCA antibody inhibits tumor formation and metastasis in orthotopic models of pancreatic cancer
Authors: Tony Navas, Trisha Haubrich, Jenny Llamas, Hector Avina, Zhang Chunying, Myra Perez, Linnette Capo, Monica Leavitt, Rou-Yu Chen, Alla Verlinsky, Zili An, James Secrest, Nandini Ganguly, Daulet Satpayev, Karen Morrison, Art Raitano, Pia Challita-Eid, Xiao-Chi Jia, Kendall Morrison, Alan Hartford, David Stover
Journal: Cancer Research (2011)

Abstract Prostate stem cell antigen (PSCA) is a cysteine-rich cell surface glycoprotein expressed in about 50% of pancreatic and prostate cancers. AGS-PSCA is a hybridoma-derived fully human IgG1κ monoclonal antibody (MAb) targeting PSCA previously reported to have anti-tumor efficacy in prostate and pancreatic tumor models. AGS-1C4D4 is a CHO-derived antibody generated from the same gene as AGS-PSCA, with similar specificity and binding affinity to PSCA (Kd = 2.0 × 10-10M). Since hybridoma and CHO-derived MAbs displayed disparate glycosylation patterns by mass spectroscopy, we further evaluated their MAb effector functions. AGS-1C4D4 was found to have more potent ADCC activity in vitro on PSCA-expressing pancreatic cell lines, HPAC and Panc0203, using human PBMCs from multiple normal donors. However, both MAbs were similarly effective in mediating CDC on PSCA-expressing recombinant B300.19 cells. Deglycosylation greatly reduced the relative ADCC and CDC activities of both MAbs compared to their intact versions. Additional studies to elucidate the role of the effector functions of AGS-1C4D4 are currently being conducted in vivo using intact and deglycosylated MAbs and will be presented. While neither intact antibody had any direct cytotoxic activity on HPAC cells in vitro, both MAbs significantly inhibited tumor formation, local invasion and metastases to distant sites in orthotopic HPAC xenograft tumor models in vivo. In addition, AGS-1C4D4 significantly inhibited the growth and metastasis of established orthotopic HPAC tumors in combination with Gemcitabine. AGS-1C4D4 is currently being evaluated in a Phase 2 clinical study for pancreatic cancer in combination with Gemcitabine. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4566. doi:10.1158/1538-7445.AM2011-4566
Indoor Tanning Among High School Students in the United States, 2009 and 2011
Authors: Gery P. Guy, Zahava Berkowitz, Eric Tai, Dawn M. Holman, Sherry Everett Jones, Lisa C. Richardson
Journal: JAMA Dermatology (2014)

Indoor tanning is associated with an increased risk of skin cancer, including melanoma, and is particularly dangerous for younger and more frequent indoor tanners.To examine the prevalence of indoor tanning and frequent indoor tanning (≥10 times during the 12 months before each survey) and their association with health-related behaviors.A cross-sectional study examined data from the 2009 and 2011 national Youth Risk Behavior Surveys, which used nationally representative samples of US high school students representing approximately 15.5 million students each survey year. The study included 25,861 students who answered the indoor tanning question.The prevalence of indoor tanning and frequent indoor tanning were examined as well as their association with demographic characteristics and health-related behaviors using multivariable logistic regression modeling.The prevalence of indoor tanning was greater among female, older, and non-Hispanic white students. Indoor tanning was highest among female students aged 18 years or older, with 31.5% engaging in indoor tanning in 2011, and among non-Hispanic white female students, with 29.3% engaging in indoor tanning in 2011. Among female students, the adjusted prevalence of indoor tanning decreased from 26.4% in 2009 to 20.7% in 2011. Among female and male students, indoor tanning was associated with other risk-taking behaviors, such as binge drinking (P < .001 and P = .006, respectively), unhealthy weight control practices (P < .001, for both), and having sexual intercourse (P < .001, for both). Additionally, indoor tanning among female students was associated with using illegal drugs (P < .001) and having sexual intercourse with 4 or more persons (P = .03); use among male students was associated with taking steroids without a physician's prescription (P < .001), smoking cigarettes daily (P = .03), and attempting suicide (P = .006). More than half of respondents engaging in indoor tanning reported frequent use of the devices.Indoor tanning is common among high school students. Public health efforts are needed to change social norms regarding tanned skin and to increase awareness, knowledge, and behaviors related to indoor tanning. The clustering of risky behaviors suggests a need for coordinated, multifaceted approaches, including primary care physician counseling, to address such behaviors among adolescents.
Abstract 4895: A cancer stem cell instigator pathway revealed by transcriptomics, stem cell mutagenesis, and in-vivo tumor initiation.
Authors: Ana Krtolica, Jacob Glanville, Gnanaratnam Giritharan, Eduardo Caceres, Erica Canino, Kyung-Ah Kim
Journal: Cancer Research (2013)

Abstract We have developed a multi-stage Cancer Stem Cell (CSC) model that recapitulates the natural process of carcinogenesis. Isogenic human embryonic stem cells (ESCs) exposed to non-biased mutagens were found to undergo rare spontaneous CSC transformation. Progenitor induced CSC (iCSC) clones exhibited classical CSC/SC marker expression, tumorsphere formation, resistance to common chemotherapeutic agents, and a capacity to form serially transplantable tumors in immunocompromised animals. A subset of progenitor clones formed tumors that took on a glioma-like morphology and produced more highly drug resistant mature CSCs that exhibited phenotypic characteristics of the primary patient glioma CSCs. Computational comparison to expression profiles of 313 human tumor lines confirmed that the mature CSCs had adopted a glioma-like expression profile. An integrated molecular model of the instigator pathway was assessed by comprehensive RNASeq transcriptomics, tandem MS proteomics, microRNA profiling, and mutagen-induced molecular polymorphisms. Progenitor iCSCs were found to have an ESC expression phenotype, significantly differing in the expression of only 32 genes, with some bearing direct evidence of mutagenesis in the expressed transcript. The instigator genes formed a proto-oncology seed pathway that was expanded by progressive expression changes to a more classical oncology profile in the glioma-like tumors and mature iCSCs derived in vivo from the progenitor iCSC. Classical oncology targets evident in the late-stage tumor model were absent in the progenitor iCSCs. However, computational repositioning analysis identified a limited set of existing molecules that could act directly to mitigate the progenitor pathway in the iCSCs. Citation Format: Ana Krtolica, Jacob Glanville, Gnanaratnam Giritharan, Eduardo Caceres, Erica Canino, Kyung-Ah Kim. A cancer stem cell instigator pathway revealed by transcriptomics, stem cell mutagenesis, and in-vivo tumor initiation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4895. doi:10.1158/1538-7445.AM2013-4895