tbuckley/cabot-search huggingface dataset:
Effect of hydralazine on perfusion and metabolism in the leg during upright bicycle exercise in patients with heart failure.
Authors: J R Wilson, J L Martin, N Ferraro, K T Weber
Journal: Circulation (1983)

The aerobic exercise capacity of patients with chronic heart failure is frequently impaired because of inadequate O2 transport to working skeletal muscle. To determine whether hydralazine improves O2 transport to working muscle, we examined the effect of intravenous hydralazine on blood flow (measured by thermodilution) and metabolism in the leg during maximal upright bicycle exercise in 10 patients with chronic heart failure. Hydralazine increased maximal exercise cardiac output (5.6 +/- 0.7 to 6.7 +/- 0.6 l/min; p less than .01) and decreased systemic O2 extraction (79 +/- 3% to 65 +/- 2%; p less than .01) but did not alter maximal O2 uptake (787 +/- 105 vs 779 +/- 82 ml/min). Leg blood flow at maximal exercise increased from 1.6 +/- 0.2 to 2.1 +/- 0.4 l/min (p less than .03); the proportion of cardiac output delivered to the leg remained unchanged (59 +/- 3% vs 57 +/- 9%). This increase in flow was associated with a decrease in O2 extraction in the leg (84 +/- 2% to 79 +/- 2%; p less than .01) and no change in peak femoral venous lactate (59.1 +/- 7.4 vs 54.1 +/- 5.3 mg/dl), suggesting that there is functional or anatomic shunting of the augmented limb flow rather than delivery to metabolizing muscle. These data suggest that hydralazine augments flow to the exercising limb in patients with heart failure but that this augmented flow does not increase oxygen availability within working muscle.
Abstract 2251: nrf2-keap1 axis molecular profile in small cell lung cancer cell lines
Authors: Lucia Anna Muscarella, Annamaria la Torre, Angelo Sparaneo, Orazio Palumbo, Clelia Tiziana Storlazzi, Teresa Balsamo, Domenico Trombetta, Fabio Pellegrini, Raffaela Barbano, Barbara Pasculli, Paolo Graziano, Montse Sanchez-cespedes, Maria Teresa Landi, Paola Parrella, Vito Michele Fazio
Journal: Cancer Research (2014)

Abstract The Keap1/Nrf2 pathway is a master regulator of antioxidants and cellular stress responses implicated in resistance of tumor cells against chemotherapeutic drugs. The link between molecular alterations of this pathway in Non Small Cell Lung Cancer (NSCLC) is well studied and appears to depend on several main factors including the existence of activating mutations in NFE2LE gene and/or loss of function mutations and methylation in the KEAP1 gene. At present, the data concerning the mechanism of alteration of Nrf2-Keap1 pathway in Small Cell Lung Cancer (SCLC) instead are almost incomplete and correlation analysis with therapeutic strategies targeting the molecular dysfunction of this pathway is ongoing. Here we present a comprehensive molecular alteration profile of the main partners of the Nrf2/keap1 axis in 12 SCLC cell lines by integrating data from SNP-Array analysis, immunofluorescence, mutation screening by direct sequencing, methylation by QMSP and expression analyses by RT-qPCR and western blotting. Our analyses confirm the global deregulation of Nrf2/Keap1 pathway in SCLC cell lines, showing an hypermethylation of the CpGs located into the P1 promoter region of the KEAP1 in 42% (5/12) of the cell lines, and a chromosomal amplification involving the NFE2LE gene locus (2q31.1) in two cell lines. Only one just described point mutation in the kelch-repeat 2 was observed in one of the cell line analysed. Our gene-alteration profile of SCLC cell lines provides new insights into the mechanism of deregulation of Nrf2-Keap1 detoxification pathway in this group of high grade neuroendocrine lung cancers, suggesting the NFE2LE gene amplification and the KEAP1 promoter hypermethylation as alternative mechanisms of dysfunctional Nrf2/Keap1 in SCLCs.Analyses on tumor tissues are ongoing to confirm these observations. Moreover, the provided full molecular data from cell lines will be useful for in vitro functional studies aimed to establish new combined therapeutic strategies in targeted cancer treatments of this aggressive lung tumor histotype. Citation Format: Lucia Anna Muscarella, Annamaria la Torre, Angelo Sparaneo, Orazio Palumbo, Clelia Tiziana Storlazzi, Teresa Balsamo, Domenico Trombetta, Fabio Pellegrini, Raffaela Barbano, Barbara Pasculli, Paolo Graziano, Montse Sanchez-cespedes, Maria Teresa Landi, Paola Parrella, Vito Michele Fazio. nrf2-keap1 axis molecular profile in small cell lung cancer cell lines. [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 2251. doi:10.1158/1538-7445.AM2014-2251
IMPORTANCE OF EARLY RECOGNITION OF CANCER OF THE UTERUS.
Authors: WM. H. HUMISTON
Journal: JAMA (1900)

The importance of early diagnosis and prompt surgical interference in carcinomatous disease of the uterus has been so repeatedly and emphatically emphasized by all writers, and the various methods and innumerable forms of technique discussed that I feel much like offering some apology for again asking your attention to the subject of carcinoma of the uterus. However, it is not so much its early diagnosis or the manifold methods of technique in vogue of which I wish to speak a few words, but the manner of its recurrence as we have but recently learned from laboratory research and clinical experience. It is well established that practically the only form of cancer which attacks the body of the uterus is the adenocarcinomatous variety. This is also of the most frequent occurrence in the cervix. The epitheliomata are usually confined to the vaginal portion of the cervix, and extend to the vaginal
Assessment of left ventricular diastolic and systolic function in patients with heart failure using steady state cine magnetic resonance imaging: Validation study using conductance catheter
Authors: Shoko Uemura, Hajime Sakuma, Munenobu Motoyasu, Katsuya Onishi, Masaki Tanabe, Kaoru Dohi, Tsutomu Okinaka, Naoki Isaka, Kan Takeda, Takeshi Nakano
Journal: Journal of the American College of Cardiology (2003)
Local Pulse Pressure and Regression of Arterial Wall Hypertrophy During Long-Term Antihypertensive Treatment
Authors: Pierre Boutouyrie, Caroline Bussy, Daniel Hayoz, Jurg Hengstler, Nathalie Dartois, Brigitte Laloux, Hans Brunner, Stéphane Laurent
Journal: Circulation (2000)

Background —Local pulse pressure (PP) is an independent determinant of carotid artery wall thickness, stronger than mean blood pressure (BP). The present study was designed to assess whether a β-adrenoceptor antagonist–based or an ACE inhibitor–based treatment was able to reduce carotid artery wall hypertrophy through a reduction in carotid PP rather than by lowering mean BP and whether the influence of local PP reduction could also be detected at the site of a muscular artery, the radial artery. Methods and Results —Ninety-eight essential hypertensive patients were randomized to 9 months of double-blind treatment with either celiprolol or enalapril. Arterial parameters were determined with high-resolution echo-tracking systems. PP was measured locally with applanation tonometry and independently of mean BP. After 9 months of treatment, mean BP, carotid PP, and intimal-medial thickness (IMT) decreased significantly, with no difference between the 2 groups. The reduction in carotid PP but not in mean BP was a major independent determinant of the reduction in carotid IMT. Radial artery IMT and PP decreased significantly with both treatments. However, the reduction in radial artery IMT was not related to the changes in radial artery PP. Conclusions —The regression of carotid artery wall hypertrophy during long-term antihypertensive treatment was dependent on the reduction in local PP rather than on the lowering of mean BP. The effect of PP lowering on IMT reduction was observed at the site of an elastic artery but not at the site of a muscular artery.
Commission plans to adopt “a lighter touch”
Authors: Caroline White
Journal: BMJ (2004)

The Healthcare Commission, the independent regulatory body charged with monitoring the quality of health services in the United Kingdom, is to set out proposals for its new assessment criteria at the end of next month. The new criteria are expected to replace or modify the present star ratings system, under which hospitals are awarded stars according to quality.

The proposals, which will be put out for wide consultation, will reflect the framework for NHS standards issued by the government in July this year in a bid to boost quality and simplify the plethora of existing performance indicators.

But …
The Plasminogen–Activating System in Hepatic Stellate Cells
Authors: H Leyland, J Gentry, M J Arthur, R C Benyon
Journal: Hepatology (1996)

Urokinase plasminogen activator (uPA) generates plasmin, a process inhibited by plasminogen–activator inhibitor (PAI)–1 and localized to the cell surface by binding of uPA to a specific receptor. Plasmin degrades extracellular matrix (ECM) both directly and by activation of matrix metalloproteinases (MMPs). Because stellate cells play a central role in the pathogenesis of liver fibrosis both via production of ECM proteins and through secretion of MMPs, their contribution to plasmin generation was assessed. Stellate cells were prepared from rat liver and cultured on plastic. Northern analysis showed cellular expression of messenger RNA (mRNA) for PAI–1, uPA, and uPA receptor. Zymography/reverse zymography identified cell–surface–associated uPA activity and uPA and PAI–1 in culture media. Net uPA activity in culture media was maximal after 7 days in culture and then declined, whereas PAI–1 antigen levels remained consistently elevated between 7 and 21 days in culture. Stellate cell–mediated plasmin generation was also seen in in vitro cultures supplemented with plasminogen. Because hepatic stellate cells (HSCs) contain retinoids and release them on activation, the effect of retinoic acid on the plasminogen–activating system was also assessed. Treatment of cultured HSCs with retinoic acid (1 μmol/L) increased uPA secretion 2.6–fold but did not alter PAI–1. We conclude that stellate cells synthesize key components of the plasminogen–activating system and generate plasmin and therefore have the ability to regulate MMP activation. Upregulation of uPA synthesis by retinoic acid may have implications in matrix remodeling in sites of stellate cell activation in which high concentrations of retinoids may be achieved.
On the Physical Death of Jesus Christ
Authors: Ronald M. Meyer
Journal: JAMA (1986)

<h3>To the Editor.—</h3> It has been a source of great pride and pleasure for me to have reviewed manuscripts for the<i>JAMA</i>staff over the last two years.The Journalseems to get better and better. However, I must tell you of my surprise and disappointment when I read the article, "On the Physical Death of Jesus Christ."1 The authors present as science material from references that are speculative, unverifiable, and open to conflicting interpretations. Some of what they write may be true, but much is creative reconstruction, stated with too much certainty. For example, the authors accept literally the biblical statement that Jesus' sweat became like blood. They diagnose hematidrosis, an exceedingly rare condition, and rely upon their tenuous diagnosis to support a conclusion that Jesus must have been hypovolemic. Detailed and horrifying figures appear. While they<i>may</i>represent what happened to Jesus, the connection between these pictures and
Accuracy of diagnosis of coronary artery disease by radionuclide management of left ventricular function during rest and exercise.
Authors: R H Jones, P McEwan, G E Newman, S Port, S K Rerych, P M Scholz, M T Upton, C A Peter, E H Austin, K H Leong, R J Gibbons, F R Cobb, R E Coleman, D C Sabiston
Journal: Circulation (1981)

Rest and exercise radionuclide angiocardiographic measurements of left ventricular function were obtained in 496 patients who underwent cardiac catheterization for chest pain. Two hundred forty-eight of these patients also had an exercise treadmill test. An ejection fraction less than 50% was the abnormality of resting left ventricular function that provided the greatest diagnostic information. In patients with normal resting left ventricular function, exercise abnormalities that were optimal for diagnosis of coronary artery disease were an injection fraction at least 6% less than predicted, an increase greater than 20 ml in end-systolic volume and the appearance of an exercise-induced wall motion abnormality. The sensitivity and specificity of the test were lower in patients who were taking propranolol at the time of study and in patients who failed to achieve an adequate exercise end point. In the 387 patients with an optimal study, the test had a sensitivity of 90% and a specificity of 58%. Radionuclide angiocardiography was more sensitive and less specific than the exercise treadmill test. The high degree of sensitivity of the radionuclide test suggests that it is most appropriately applied to patient groups with a high prevalence of disease, including those considered for cardiac catheterization.
Immunogenetic, Clinical, and Demographic Characterization of Childhood Type I Diabetes in New Zealand
Authors: Louisa V Forbes, Russell S Scott, Laurie J Brown, Brian A Darlow
Journal: Diabetes Care (1995)

To examine the relationship between genetic susceptibility alleles and islet cell antibodies (ICAs) in type I diabetes.The human leukocyte antigen (HLA)-DQB1 alleles and ICA levels of all incident type I diabetic cases in patients < 20 years of age diagnosed in 1990 and 1991 in Canterbury, New Zealand, were determined.The mean annual incidence rate for type I diabetes over the 24 months was 19.0/100,000 patient-years (95% confidence interval [CI] 13.5-26.0/100,000), which was considerably higher than rates observed between 1982 and 1989 (11.7/100,000; 95% CI 9.6-14.3/100,000). ICAs > or = 10 Juvenile Diabetes Foundation units (JDF U) were present in 84.6% of the subjects, but there was a higher prevalence of ICA-negative (ICA-) subjects among those diagnosed during the winter months. The frequencies of the susceptibility allele DQB1*0302 and susceptibility genotype 0302/0201 were 71.8% and 43.5%, respectively. Subjects with 0302 tended to be younger (mean age 8.3 +/- 5.1 years) than those with nonsusceptibility types (mean age 11.8 +/- 4.7 years, P = 0.056). The probability of being ICA positive (ICA+) was not significantly different between subjects with allele 0302 (85.7%) and those without it (81.8%). All seven patients negative for ICA were homozygous for DQB1 nonaspartate-57. There was no clustering of the immunogenetic markers with demographic and clinical characteristics apart from age at diagnosis.No direct relationship was observed between DQB1-defined genetic susceptibility and ICA at diagnosis, suggesting that variations at the DQB1 locus are not linked to the expression of this autoimmune marker of beta-cell destruction.
B-type natriuretic peptide predicts left ventricular response to surgery in patients with severe mitral regurgitation in asymptomatic patients with preserved left ventricular function
Authors: W.H.Wilson Tang, Richard W. Troughton, Deborah A. Agler, Kathy Morris, Gary S. Francis, Jianxin Qin, Brian P. Griffin
Journal: Journal of the American College of Cardiology (2003)
Predictors of New-Onset Kidney Disease in a Community-Based Population
Authors: Caroline S. Fox
Journal: JAMA (2004)

Kidney disease is associated with an increased risk for the development of cardiovascular disease and end-stage renal disease; however, risk factors for kidney disease have not been well studied.To identify predictors of the development of new-onset kidney disease.A community-based, longitudinal cohort study of 2585 participants who attended both a baseline examination in 1978-1982 and a follow-up examination in 1998-2001, and who were free of kidney disease at baseline.Kidney disease was assessed by the Modification of Diet in Renal Disease Study equation and defined by a glomerular filtration rate (GFR) in the fifth or lower percentile (< or =59.25 mL/min per 1.73 m2 in women, < or =64.25 mL/min per 1.73 m2 in men). Stepwise logistic regression was used to determine the impact of risk factors on the occurrence of new-onset kidney disease. Baseline and long-term, 12-year, averaged risk factor models were explored.At baseline, there were 1223 men and 1362 women, with a mean age of 43 years, who were free of preexisting kidney disease. After a mean follow-up of 18.5 years, 244 participants (9.4%) had developed kidney disease. In multivariable models, baseline age (odds ratio [OR], 2.36 per 10-year increment; 95% confidence interval [CI], 2.00-2.78), GFR (<90 mL/min per 1.73 m2: OR, 3.01; 95% CI, 1.98-4.58; 90-119 mL/min per 1.73 m2: OR, 1.84; 95% CI, 1.16-2.93), body mass index (OR, 1.23 per 1 SD; 95% CI, 1.08-1.41), diabetes (OR, 2.60; 95% CI, 1.44-4.70), and smoking (OR, 1.42; 95% CI, 1.06-1.91) were related to the development of kidney disease. In addition to baseline age and GFR, the long-term, averaged risk factors that were predictive of kidney disease included hypertension (OR, 1.57; 95% CI, 1.17-2.12), high-density lipoprotein cholesterol level (OR, 0.80 per 1 SD; 95% CI, 0.69-0.92), and diabetes (OR, 2.38; 95% CI, 1.45-3.92). Compared with a normal GFR (> or =120 mL/min per 1.73 m2), a mildly reduced GFR (<90 mL/min per 1.73 m2) predicted a 3-fold odds of progression to kidney disease (OR, 2.95; 95% CI, 1.94-4.49).Established cardiovascular disease risk factors are associated with the development of new-onset kidney disease. Patients with a mildly reduced GFR should be monitored for progression to kidney disease.
Agencies warn of escalating food crisis in north Africa
Authors: P. Moszynski
Journal: BMJ (2010)

Oxfam and other relief agencies have appealed for emergency aid to avert an impending famine in Africa’s Sahel region, complaining that the crisis has been worsened by a late and inadequate response by international donors.

Last week the UN Food and Agricultural Organization’s global information and early warning system warned that the food situation in the region is of “grave concern, with over 10 million people at risk of hunger.”

It says that the food crisis is affecting people in several countries: 7.8 million in Niger, two million in Chad, 258 000 in Mali, and 370 000 in Mauritania. Some communities in …
How to control the misuse of health services
Authors: W. G Pickering
Journal: BMJ (1996)

Many people see their doctor unnecessarily or for trivial matters. Furthermore, many are not satisfied with what they are told and insist on this or that form of investigation, referral, or treatment, which always costs money.

The very suggestion that people might be abusing medical services is not often discussed in medicopolitical circles and risks a storm of controversy and accusations of an uncaring attitude. It is as though patients—like customers in business—are always right. They must be indulged at the medical temple, even if their supposedly medical problems are entirely fanciful.

The profession's outward diplomatic silence is by no means mirrored by silence within. There is continual noisy agitation at the miscellaneous problems deemed by some consumers as medical and worthy of professional and sometimes urgent attention. The low medical morale so often referred to now is likely to be partly related to this situation. There is nothing quite so dispiriting in any walk of life as feeling that you are being manipulated and …
Extrapolation of animal carcinogenicity data: limitations and pitfalls.
Authors: M D Hogan
Journal: Environmental Health Perspectives (1983)

Laboratory-generated animal bioassay data often serve as the basis for estimating potential human cancer risk. However, there is no single procedure that has been universally accepted as the method of choice for extrapolating experimentally observed results to the low exposure levels that are generally of public health concern. All of the models proposed to date suffer from various limitations. Therefore, the most prudent approach may be to rely primarily on the more conservative procedures such as linear extrapolation until a better understanding of the biological mechanisms underlying the process of carcinogenesis is attained. In addition to the choice of an extrapolation model, there are a variety of other factors, such as the incorporation of background cancer rates, the potential for synergistic reactions, differential pharmacokinetic effects and differences in exposure regimen, that can have a significant bearing on the extrapolation of animal carcinogenicity data to man.
Metastasis to the appendix from gastric cancer detected incidentally on colonoscopy
Authors: K. Fu, T. Horimatsu, Y. Sano, A. Katagiri, Y. Kaji, T. Fujimori
Journal: Endoscopy (2007)

A 59-year-old man complaining of anal pain was referred to our division for investigation. His medical history included a total gastrectomy for advanced poorly differentiated gastric adenocarcinoma, which had penetrated the serosa without invasion of adjacent structures or peritoneal dissemination. Colonoscopy revealed that the appendiceal orifice was generally elevated, as if pushed up by a solid appendiceal mass (Figure [1]). In addition, coarse, reddish mucosa was detected at the appendiceal orifice (Figure [2]). Histological examination of the biopsy specimens taken from the mucosa at the appendiceal orifice during colonoscopy revealed poorly differentiated adenocarcinoma, consistent with metastasis from the gastric carcinoma that had been surgically resected 1 year previously. Unfortunately, the patient died 1 year after receiving systemic chemotherapy.
Inflammatory bowel disease incidence: up, down or unchanged?
Authors: RICHARD F A LOGAN
Journal: Gut (1998)

One of the few aspects of the epidemiology of inflammatory bowel disease (IBD) that seems indisputable is the emergence of both ulcerative colitis and Crohn’s disease in the economically developed nations of Western Europe and North America during the past century.1 Some of the apparent increase in incidence undoubtedly reflects a receding tide of mimicking infectious diseases and developments in endoscopic and other diagnostic techniques. Nevertheless, most epidemiologists accept that there were considerable real increases in ulcerative colitis incidence during the first half of this century and of Crohn’s disease incidence during the middle half-century in these countries.2 As the millennium approaches, are the incidences of each disease continuing to increase? Some reports suggest they are, whereas claims that Crohn’s disease incidence is no longer increasing can provoke a rapid response from some clinicians.3-6 At a time when basic science is making progress by leaps and bounds, why should such an apparently simple epidemiological question prove so difficult to answer, and does it matter?

Assessing time trends in the incidence of most chronic diseases is difficult and IBD poses particular problems. Firstly, the data routinely collected on mortality and morbidity from IBD are of little help. In most countries over 75% of deaths attributed to IBD are in the elderly and mortality rates are a twentieth or less of the incidence figures for the same period. Although national mortality statistics show a broad correlation with individual incidence studies from those countries, the relation between mortality and incidence within countries is weak, such that during the 1950s and 1960s mortality rates from Crohn’s disease in England and Wales and the USA showed a small less than twofold increase when individual studies of Crohn’s disease incidence were showing much larger increases.7 8 Over the same period ulcerative colitis …