tbuckley/cabot-search huggingface dataset:
Ribavirin mutagenesis: Hidden clues in mathematical models
Authors: Zhi Hong, Hartmut Jaeschke, Kevin Mullen, Darius Moradpour
Journal: Hepatology (2005)

Nearly 200 million individuals worldwide are currently infected with hepatitis C virus (HCV). Combination therapy with pegylated interferon and ribavirin, the latest treatment for HCV infection, elicits long-term responses in only about 50% of patients treated. No effective alternative treatments exist for nonresponders. Consequently, significant efforts are continuing to maximize response to combination therapy. However, rational therapy optimization is precluded by the poor understanding of the mechanism(s) of ribavirin action against HCV. Ribavirin alone induces either a transient early decline or no decrease in HCV viral load, but in combination with interferon it significantly improves long-term response rates. Here we present a model of HCV dynamics in which, on the basis of growing evidence, we assume that ribavirin decreases HCV infectivity in an infected individual in a dose-dependent manner. The model quantitatively predicts long-term response rates to interferon monotherapy and combination therapy, fits observed patterns of HCV RNA decline in patients undergoing therapy, reconciles conflicting observations of the influence of ribavirin on HCV RNA decline, provides key insights into the mechanism of ribavirin action against HCV, and establishes a framework for rational therapy optimization.
Mortality associated with moderate intakes of wine, beer, or spirits
Authors: M. Gronbaek, A. Deis, T. I A Sorensen, U. Becker, P. Schnohr, G. Jensen
Journal: BMJ (1995)

To examine the association between intake of different types of alcoholic drinks and mortality.Prospective population study with baseline assessment of alcohol intake, smoking habit, income, education, and body mass index, and 10-12 years' follow up of mortality.Copenhagen city heart study, Denmark.6051 men and 7234 women aged 30-70 years.Number and time of cause-specific deaths from 1976 to 1988.The risk of dying steadily decreased with an increasing intake of wine--from a relative risk of 1.00 for the subjects who never drank wine to 0.51 (95% confidence interval 0.32 to 0.81) for those who drank three to five glasses a day. Intake of neither beer nor spirits, however, was associated with reduced risk. For spirits intake the relative risk of dying increased from 1.00 for those who never drank to 1.34 (1.05 to 1.71) for those with an intake of three to five drinks a day. The effects of the three types of alcoholic drinks seemed to be independent of each other, and no significant interactions existed with sex, age, education, income, smoking, or body mass index. Wine drinking showed the same relation to risk of death from cardiovascular and cerebrovascular disease as to risk of death from all causes.Low to moderate intake of wine is associated with lower mortality from cardiovascular and cerebrovascular disease and other causes. Similar intake of spirits implied an increased risk, while beer drinking did not affect mortality.
International Comparisons of IDDM Mortality: Clues to Prevention and the Role of Diabetes Care
Authors: Thomas J Songer, Kimberly DeBerry, Ronald E LaPorte, Jaakko Tuomilehto
Journal: Diabetes Care (1992)

A striking difference in all-cause mortality has been noted between individuals with insulin-dependent diabetes mellitus (IDDM) from Finland and Allegheny County, PA. Mortality rates among people 25-37 yr of age from the Allegheny County IDDM Registry were over two times greater than the rates observed from the Finland IDDM Registry. Applying the Finnish rate to the structure of the IDDM population from Allegheny County suggests that about one-half of the deaths in the Allegheny County cohort may be theoretically preventable. Most deaths that might be avoided appear to be caused by the acute complications of diabetes. Deaths from acute-related causes were higher (as a proportion of all deaths) in the Allegheny County cohort than in Finland (46.2 vs. 33.3%). There is some indication that barriers to health care may be present among individuals with IDDM in the United States. Individuals without health insurance from the Children's Hospital IDDM Registry in Pittsburgh had fewer physician visits than those with insurance. Even for those with insurance, out-of-pocket health-care expenses were significant. People with lower household incomes (less than $20,000) spent more, as a percentage of their income, on medical supplies than those with higher incomes and may have been less likely to monitor blood glucose levels and visit an eye doctor because of it. These findings suggest that health system barriers, such as the access to care and the financial burden of diabetes care, in the United States may be affecting the health of adults with IDDM. Further investigation is needed to clarify the extent of barriers to care in IDDM and their contribution to adverse health outcomes.
The Theory and Practice of Public Health
Authors: Vlado A. Getting, Claire F. Ryder
Journal: New England Journal of Medicine (1953)

RAPID developments in the theory and practice of public health in the past decade have been brought about by the discoveries in the medical sciences, by the changing pattern of community organization and finally by the relatively decreased importance of infectious diseases as compared with chronic illness. In 1948 the American Board of Preventive Medicine was incorporated, thereby giving public health an equal status with other specialties of medicine. The public, as well as the medical profession, has become more conscious of public-health programs. The health education programs of the medical societies, health departments, insurance companies and the public press . . .
Abstract 1372: The methylome of ER-negative tumors is predominantly hypermethylated
Authors: Maria J. Worsham, Dhananjay Chitale, Kang Mei Chen, George Divine
Journal: Cancer Research (2014)

Abstract The biological significance of DNA methylation in the regulation of gene expression and its role in cancer is increasingly recognized. The underlying hypothesis of this study is that strategic global approaches will identify aberrantly methylated genes that underlie the pathogenesis of ER-negative (ER-) breast cancer (BC). We used the Infinium HumanMethylation450 BeadChip to profile the methylome of ER- breast cancers to determine differentially methylated genes. The 450K array includes 485,577 cytosine positions of the human genome. Whole genomic DNA from 40 primary ER-, 40 ER positive (ER+), and 40 normal breast tissue samples were assayed for genome-wide methylation. Data were analyzed by GenomeStudio software (Illumina). Degree of methylation was calculated as a β-value (ranging from 0 to 1) and M-values [log (β/ (1- β)] were used for significance tests. With 30 sets of paired tumor/normal tissue, GEE was performed to account for their correlation. To identify methylated genes associated with ER- subtypes and distinct from ER+, a 3-tiered approach to call out genes in which methylation changed dramatically between ER+ and ER- subtypes was used. Tier 1: computed adjusted FDR values for all CpGs/ (or their averages for each gene) to be 0.05 or lower. Tier 2: the CpGs/genes to include genes with a 2-fold change (ratio &amp;gt;= 2.0 or ratio &amp;lt;= 0.5). Tier 3: CpGs/genes to include genes with an absolute difference between the mean β of =&amp;gt;0.2. Differentially methylated genes (DMGs) at tier 3 for the different comparison groups were as follows: all BC (n=80) vs normal (n=40): 1070 DMGs: 1001: hypermethylated, 69: hypemethylated; ER+ vs normal: 1720: 1518 hyper, 202 hypo; ER- vs normal: 1170, 1085 hyper, 85 hypo; ER- vs ER+ vs: 289, 191 hyper, 97 hypomethylated. Overall, ER- BC tumors were more hypermethylated than hypomethylated when compared to normal breast tissue and ER+ BC. Estrogen receptor-negative BC is a more aggressive form than ER positive BC with approximately double the incidence in African Americans than in Caucasian Americans. The emerging differential methylation pattern would further help stratify them into distinct subgroups. Promotor methylation being potentially reversible, methylated genes may serve as future molecular targets for demethylating therapies. Support: Komen Foundation: KG110218 Citation Format: Maria J. Worsham, Dhananjay Chitale, Kang Mei Chen, George Divine. The methylome of ER-negative tumors is predominantly hypermethylated. [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 1372. doi:10.1158/1538-7445.AM2014-1372
Prostate cancer patients get worse care than other cancer patients
Authors: Susan Mayor
Journal: BMJ (2006)

Patients with cancer are receiving better care from the NHS in England than five years ago, but many are still waiting too long to see a specialist after being referred by their GP, a new report says. It warns that provision of specialist care for prostate cancer is a lower priority than for other common cancers.

The report, Tackling Cancer: Improving the Patient Journey , assessed the progress made since the introduction of the NHS Cancer Plan, a national strategy introduced in 2000 to improve cancer services. The plan was based on a range of information on service provision, including …
Abortion
Authors: Charles V. Ford
Journal: JAMA (1971)

Forty consecutive women of lower socioeconomic status who had requested therapeutic abortion were studied psychiatrically and psychologically. Thirty were approved for abortion because continuation of pregnancy was believed to represent a substantial risk to their mental health. Twenty-two of this group were seen again in follow-up six months later. Although a mild depression was common following abortion, the majority had fewer psychiatric symtoms. Statistically significant changes in average MMPI scores confirmed the clinical impression that for most women the abortion had been therapeutic. Three of the 22 women (14%) were more disturbed when seen in follow-up, but their increased discomfort could not be related definitely to the abortion since each had a history of serious psychiatric problems prior to abortion.
ST-ELEVATION MYOCARDIAL INFARCTION IS OFTEN DUE TO INFECTION WITH PATHOGENIC BACTERIA ASSOCIATED WITH PERIODONTAL DISEASE
Authors: Jussi Mikkelsson, Tanja Pessi, Pasi P. Karjalainen, Antti Ylitalo, Juhani Airaksinen, Pekka J. Karhunen
Journal: Journal of the American College of Cardiology (2011)
Primary care duped: the government's bill will wreck the NHS
Authors: Peter Bailey
Journal: BMJ (2012)

How have we got into such a mess? How can people who have devoted the whole of their working lives to the principles of the NHS been so compliant, misled, or trampled on (depending on your perspective) in the bungled reorganisations triggered by the Health and Social Care Bill that is now before the upper chamber?

I have worked for the past 12 years as a general practitioner in Health Secretary Andrew Lansley’s backyard, setting up a new general practice to serve the people arriving in the green field development of Cambourne (population 9000 and aiming for 11 000). The practice has championed holistic care with the autonomy of the patient, a right to information, and respect for the patient’s expertise at the heart of the service.

I chaired the local medical committee, and until recently I was vice chair of our emerging primary care consortium as it morphed into a clinical commissioning group.

So I have to put up my hand and say that this mess is my fault. …
Direct percutaneous endoscopic jejunostomy tube placement using a fine needle for jejunal anchoring
Authors: A. Karhadkar, M. Rengen, E. Dubin, H. Schwartz, S. Dutta
Journal: Endoscopy (2006)

Percutaneous endoscopic gastrojejunostomy (PEGJ) tube placement is a technically simple procedure that is the most commonly used method of endoscopic jejunostomy. However, it only allows the placement of jejunostomy tubes with a diameter of 3 - 4 mm (9 - 12 Fr), which are prone to luminal occlusion and migration [1] [2] [3]. In addition, it has been reported that PEGJ tubes may not prevent aspiration resulting from frequent retrograde tube migration into the stomach and reflux of intestinal contents [1] [2] [3]. Direct percutaneous endoscopic jejunostomy (DPEJ) appears to be a better alternative to PEGJ, as it allows placement of the larger-diameter DPEJ tube in the proximal jejunum and is associated with a reduced risk of pulmonary aspiration. However, the smaller lumen, mobility, active peristalsis of the jejunal loop, and difficulty in transillumination make this procedure much more difficult than PEGJ tube placement. To overcome the above challenges, we anchored the jejunum against the abdominal wall with a 21-gauge finder needle before passing the needle and trochar (Figures 1, 2). In addition to stabilizing the jejunum, the finder needle penetrates the soft tissue easily and is less likely to cause visceral trauma. We carried out DPEJ tube placement using this method in 21 patients for the indications listed in Table 1. The method was successful and resulted in proper placement of DPEJ tubes in 17 patients (a success rate of 81 %). In four patients, DPEJ tube placement could not be completed due to an inability to achieve adequate transillumination. No significant or major complications were associated with the procedure. Minor complications in two patients included cellulitis and cutaneous leakage of enteral contents. On the basis of this experience, it appears that DPEJ tube placement with this method is a safe and effective means of providing prolonged jejunal nutrition. Similar observations have been reported by other investigators [4] [5]. We believe that the application of this modified technique could lead to wider acceptance of DPEJ tube placement in clinical gastroenterology.
Allergen cross‐reactivity between <i>Pityrosporum orbiculare</i> and <i>Candida albicans</i>
Authors: X. Huang, S. G. O. Johansson, A. Zargari, S.L Nordvall
Journal: Allergy (1995)

Pityrosporum orbiculare and Candida albicans extracts were separated bySDS‐PAGE, and IgE binding was detected by immunoblotting with 21 patient sera that were RAST positive to both yeasts. Cross‐wise inhibition was performed of IgE binding of a serum pool containing IgE antibodies to both yeasts. The pool was mixed with serial dilutions of P. orbiculare or C. albicans extracts, and incubated with strips containing separated allergen. IgE binding was quantified by densitometric scanning and percent inhibition was calculated as well as the respective ratios between required extract concentration for 50% inhibition in heterologous compared to homologous inhibition for each component ‘inhibition ratio). Ten componentsof P. orbiculare were detected by more than 60% of the sera. IgE binding toC. albicans was weak, and only to four bands was IgE binding detected by more than 30% of the sera. The most important C. albicans allergen was a 48‐kDa band, to which IgE of half of the patient sera bound. There was little inhibition of IgE binding to P. orbiculare with C. albicans. Thus, all but three components exhibited an inhibition ratio higher than 100.The inhibition ratio of the 48‐kDa C. albicans compound was 50, thus indicating some degree of cross‐reactivity. Significant cross‐reactivity was shown by C. albicans compounds of 18, 24, 26, 34, and 38 kDa, the inhibition ratios of which were less than 10. There was some degree of cross‐reactivity between apparent protein allergens of the two yeasts, but IgE antibodies to C. albicans donot merely reflect sensitization to P. orbiculare.
Efficacy and Safety of Everolimus in Elderly Patients With Metastatic Renal Cell Carcinoma: An Exploratory Analysis of the Outcomes of Elderly Patients in the RECORD-1 Trial
Authors: Camillo Porta, Emiliano Calvo, Miguel A. Climent, Ulka Vaishampayan, Susanne Osanto, Alain Ravaud, Sergio Bracarda, Thomas E. Hutson, Bernard Escudier, Viktor Grünwald, Dennis Kim, Ashok Panneerselvam, Oezlem Anak, Robert J. Motzer
Journal: European Urology (2012)
Multiple Pacemaker Sites in Spontaneously Active Vascular Muscle
Authors: KENT HERMSMEYER
Journal: Circulation Research (1973)

Multiple-electrode extracellular recording was used to determine the degree to which membrane electrical activity spreads through the rat anterior mesenteric-hepatic portal vein. Glass-pore electrodes filled with physiological salt solution were placed against the isolated intact vein or longitudinal strips of vein at 1-mm intervals to record spontaneous spiking. No pressure electrode effect was found in the rat portal vein. Patterns and amplitudes of spiking indicated that spike activity was conducted for only a few millimeters. Multiple pacemaker sites and decremental conduction were found in both normal physiological solution and solution in which calcium concentration was halved or doubled and potassium concentration was doubled or tripled. An average of three or four pacemaker sites was found in all solutions. Approximate equipotential contours were constructed from a grid map of average spike amplitudes, and they showed the multiple regions of high-amplitude spiking, the nonuniform spatial decay of spike amplitude, and the shift of high-amplitude sites with time.
A Pathologic Department.
Authors: Walter L. Bierring
Journal: JAMA (1899)

<h3>To the Editor:</h3> —In the December 2 issue of theJournalI note with pleasure a letter from Dr. Frank B. Wynn recommending the inauguration of pathologic exhibits at the meetings of theAmerican Medical Association, and I earnestly hope that the Executive Committee of theAssociationwill favorably consider the suggestions contained therein. I feel sure that all who had the pleasure of examining the pathologic exhibit of the Indiana State Medical Society at Columbus, Ohio, will indorse and recognize this unique innovation in society work as a feature of great interest and practical benefit, and it would seem unnatural if other states did not soon follow the excellent example. If the favorable editorial mention that this movement has received generally is at all significant, the establishing of a department of pathology in the NationalAssociationmust appeal to all those interested in the promotion of scientific medicine. If
Macrophage heterogeneity in liver injury and fibrosis
Authors: Frank Tacke, Henning W. Zimmermann
Journal: Journal of Hepatology (2014)

Hepatic macrophages are central in the pathogenesis of chronic liver injury and have been proposed as potential targets in combatting fibrosis. Recent experimental studies in animal models revealed that hepatic macrophages are a remarkably heterogeneous population of immune cells that fulfill diverse functions in homeostasis, disease progression, and regression from injury. These range from clearance of pathogens or cellular debris and maintenance of immunological tolerance in steady state conditions; central roles in initiating and perpetuating inflammation in response to injury; promoting liver fibrosis via activating hepatic stellate cells in chronic liver damage; and, finally, resolution of inflammation and fibrosis by degradation of extracellular matrix and release of anti-inflammatory cytokines. Cellular heterogeneity in the liver is partly explained by the origin of macrophages. Hepatic macrophages can either arise from circulating monocytes, which are recruited to the injured liver via chemokine signals, or from self-renewing embryo-derived local macrophages, termed Kupffer cells. Kupffer cells appear essential for sensing tissue injury and initiating inflammatory responses, while infiltrating Ly-6C+ monocyte-derived macrophages are linked to chronic inflammation and fibrogenesis. In addition, proliferation of local or recruited macrophages may possibly further contribute to their accumulation in injured liver. During fibrosis regression, monocyte-derived cells differentiate into Ly-6C (Ly6C, Gr1) low expressing 'restorative' macrophages and promote resolution from injury. Understanding the mechanisms that regulate hepatic macrophage heterogeneity, either by monocyte subset recruitment, by promoting restorative macrophage polarization or by impacting distinctive macrophage effector functions, may help to develop novel macrophage subset-targeted therapies for liver injury and fibrosis.
A1-02: A need to standardize post-operative radiotherapy (PORT) fields used for non-small cell lung cancer (NSCLC): analysis of an international dummy-run study
Authors: Suresh Senan, Cecile Le Péchoux, Femke Spoelstra, Satoshi Ishikura, Francesc Casas, David Ball, Allan Price, Dirk Deruysscher, John R. van Sörnsen de Koste
Journal: Journal of Thoracic Oncology (2007)
How can we get better at providing patient centred care: does continuity matter?
Authors: C. Paddison
Journal: BMJ (2015)

<h3>Abstract</h3> Physiologically based metabolic studies usually search for easy, sensitive, and cheap techniques to rapidly estimate biological parameters such as nutrient content. Colorimetric methods to estimate carbohydrates have been extensively used (over 120,000 references). However, sugar alcohols are underestimated under conventionally used analytical conditions, in particular if using the popular van Handel method. This may lead to misinterpretations of sugar implications in biological systems. We determined the anthrone reaction with various sugar alcohols and non-alcohols individually under standard conditions (Van Handel 1985). We then manipulated the proportion of either sugar alcohols or non-alcohols in three different sugar mixtures in order to estimate the impact on the total sugar estimation. In the case of a mixture with over 50% of sugar alcohols, total sugars are underestimated by 50% when using glucose as standard.
Mumps pancreatitis without parotitis.
Authors: K Naficy, R Nategh, H Ghadimi
Journal: BMJ (1973)

chromium throughout the body is fairly uniform.With these assumptions the maximum increase in concentratoin of chrom- ium in equilibrium throughout the whole body is calculated to be 0 5 p.p.m. and the average increase 0-2 p.p.m.Although the assumptions may have been adequate for giving guidance on radiological protection they are of doubtful value for determining the change in concentration of chromium in organs due to wear products from implants.It is therefore suggested that further work should be undertaken to check the biological half life and the distribution of chromium in the body.We are most grateful for the help given by Dr.
Naltrexone Improves Blood Glucose Control in Type 1 Diabetic Women With Severe and Chronic Eating Disorders
Authors: Isabelle Raingeard, Philippe Courtet, Eric Renard, Jacques Bringer
Journal: Diabetes Care (2004)

Eating disorders are frequent causes of chronic failure of blood glucose control in young type 1 diabetic women (1) that result in a high incidence of diabetic complications (2). Moreover, severe disorders such as bulimia and binge eating are commonly associated with inappropriate compensatory behaviors to avoid weight gain, including self-induced vomiting, insulin misuse, laxative or diuretic surreptitious intake, and hyperactivity (3). Because these impulsive attitudes develop as addictions, naltrexone, an antagonist of endogenous opiates that is currently used to help weaning off alcohol, opiates, or heroin, might be considered a potentially effective therapy. Of note, recent data (4) report significant improvements obtained with naltrexone in bulimic patients, reinforcing the hypothesis of an opioid-mediated dependence.

To assess the effectiveness of naltrexone in type 1 diabetic women presenting bulimia or binge eating, we conducted an open-label, 1-year pilot trial in 10 patients affected by these eating disorders who did not respond to antidepressive drugs, behavioral therapy, and interpersonal psychotherapy. All patients volunteered and gave their informed consent to enter the trial, which was ethically approved. Mean age of the patients was 22 …