tbuckley/cabot-search huggingface dataset:
Roles of Drinking Pattern and Type of Alcohol Consumed in Coronary Heart Disease in Men
Authors: Kenneth J. Mukamal, Katherine M. Conigrave, Murray A. Mittleman, Carlos A. Camargo, Meir J. Stampfer, Walter C. Willett, Eric B. Rimm
Journal: New England Journal of Medicine (2003)

Although moderate drinking confers a decreased risk of myocardial infarction, the roles of the drinking pattern and type of beverage remain unclear.We studied the association of alcohol consumption with the risk of myocardial infarction among 38,077 male health professionals who were free of cardiovascular disease and cancer at base line. We assessed the consumption of beer, red wine, white wine, and liquor individually every four years using validated food-frequency questionnaires. We documented cases of nonfatal myocardial infarction and fatal coronary heart disease from 1986 to 1998.During 12 years of follow-up, there were 1418 cases of myocardial infarction. As compared with men who consumed alcohol less than once per week, men who consumed alcohol three to four or five to seven days per week had decreased risks of myocardial infarction (multivariate relative risk, 0.68 [95 percent confidence interval, 0.55 to 0.84] and 0.63 [95 percent confidence interval, 0.54 to 0.74], respectively). The risk was similar among men who consumed less than 10 g of alcohol per drinking day and those who consumed 30 g or more. No single type of beverage conferred additional benefit, nor did consumption with meals. A 12.5-g increase in daily alcohol consumption over a four-year follow-up period was associated with a relative risk of myocardial infarction of 0.78 (95 percent confidence interval, 0.62 to 0.99).Among men, consumption of alcohol at least three to four days per week was inversely associated with the risk of myocardial infarction. Neither the type of beverage nor the proportion consumed with meals substantially altered this association. Men who increased their alcohol consumption by a moderate amount during follow-up had a decreased risk of myocardial infarction.
Risk of Nosocomial Infection with Human T-Cell Lymphotropic Virus Type III/Lymphadenopathy-Associated Virus in a Large Cohort of Intensively Exposed Health Care Workers
Authors: Henderson Dk, Saah Aj, Zak Bj, Kaslow Ra, Lane Hc, Folks T, Blackwelder Wc, Schmitt J, LaCamera Dj, Masur H
Journal: Annals of Internal Medicine (1986)

To assess the risk of nosocomial transmission of human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV), we prospectively evaluated a cohort of 531 health care workers. One hundred fifty of these employees reported percutaneous or mucous membrane exposures to blood or body fluids from a patient with the acquired immunodeficiency syndrome (AIDS) during the treatment of 238 such patients since 1981. None of these 150 employees had serologic evidence of HTLV-III/LAV infection on follow-up from 6 to 46 months after exposure. Of the 150, 46 were studied immunologically and 29 had lymphocytes cultured for HTLV-III/LAV. Results of all studies were normal. Of the 531 employees, 3 (0.56%) had serologic evidence of HTLV-III/LAV infection. All were seropositive at the time of study entry; none reported adverse nosocomial exposures. All acknowledged membership in one or more established risk groups for AIDS. This study provides strong evidence that the risk of nosocomial transmission of HTLV-III/LAV is extremely low.
In vitro and in vivo approaches to study angiogenesis in the pathophysiology and therapy of endometriosis
Authors: Matthias W. Laschke, Michael D. Menger
Journal: Human Reproduction Update (2007)

Endometriosis represents one of the most common gynaecological disorders. According to the implantation theory, angiogenesis is a major prerequisite for the initiation and progression of the disease. Thus, during the last decade, many studies have focused on the mechanisms regulating angiogenesis in endometriotic lesions. For this purpose, sophisticated in vitro and in vivo approaches have been established, which are highlighted in this review. Enzyme-linked immunosorbent assays demonstrate the imbalance of pro- and anti-angiogenic growth factors in isolated peritoneal fluid from endometriosis patients. Histological, immunohistochemical and gene expression analyses of endometriotic tissue provide detailed information on the angio-architecture of endometriotic lesions and the different growth factor expression by various cell populations. Moreover, cell culture systems are useful tools for the identification of hormonal and immunological factors involved in the angiogenic process. Finally, sophisticated in vivo models, such as rodent models of peritoneal endometriosis as well as the chorioallantoic membrane assay and the dorsal skinfold chamber, allow for the detailed analysis of blood vessel development in ectopic endometrium and the efficacy of angiogenesis inhibitors. The findings resulting from all these approaches will help to provide better insights into the pathophysiology of endometriosis and to establish new anti-angiogenic treatment strategies for the future.
Effect of a change to mite-free bedding on children with mite-sensitive asthma: a controlled trial.
Authors: M L Burr, E Neale, B V Dean, E R Verrier-Jones
Journal: Thorax (1980)

Twenty-one children with mite-sensitive asthma took part in a crossover randomised controlled trial of mite-free bedding. Each child was issued with a new sleeping bag and pillow for a month, and twice-daily peak flow readings were compared with those obtained during a month in the child's ordinary bedding. Seventeen of the children had higher mean peak flow readings during the period in the mite-free bedding (p < 0.01). The overall improvement was only modest, however, and some mites had appeared in most of the bedding by the end of the trial. New bedding may be helpful to patients with mite-sensitive asthma, but methods are needed to prevent colonisation by mites.
Effect of Cytotoxic Chemotherapy on Markers of Molecular Age in Patients With Breast Cancer
Authors: Hanna K. Sanoff, Allison M. Deal, Janakiraman Krishnamurthy, Chad Torrice, Patrick Dillon, Jessica Sorrentino, Joseph G. Ibrahim, Trevor A. Jolly, Grant Williams, Lisa A. Carey, Amy Drobish, Brittaney-Belle Gordon, Shani Alston, Arti Hurria, Karin Kleinhans, K. Lenhard Rudolph, Norman E. Sharpless, Hyman B. Muss
Journal: JNCI Journal of the National Cancer Institute (2014)

Background Senescent cells, which express p16INK4a , accumulate with aging and contribute to age-related pathology. To understand whether cytotoxic agents promote molecular aging, we measured expression of p16INK4a and other senescence markers in breast cancer patients treated with adjuvant chemotherapy.
Prognostic role of the extent of peritumoral vascular invasion in operable breast cancer
Authors: M. Colleoni, N. Rotmensz, P. Maisonneuve, A. Sonzogni, G. Pruneri, C. Casadio, A. Luini, P. Veronesi, M. Intra, V. Galimberti, R. Torrisi, S. Andrighetto, R. Ghisini, A. Goldhirsch, G. Viale
Journal: Annals of Oncology (2007)
EDRF increases cyclic GMP in platelets during passage through the coronary vascular bed.
Authors: U Pohl, R Busse
Journal: Circulation Research (1989)

It was investigated whether endothelium-derived relaxing factor (EDRF) increases cyclic GMP (cGMP) content in platelets passing through the coronary bed. Boluses of washed platelets from healthy human donors were injected into the aortic perfusion line of isolated, saline-perfused rabbit hearts under constant flow conditions (28 +/- 2 ml/min). The coronary effluent was collected over 5 seconds, and the cGMP content of platelets was determined by radioimmunoassay. Platelet cGMP amounted to 0.34 +/- 0.11 pmol/mg protein after passage through the unstimulated coronary bed. During stimulation with acetylcholine (1 microM), it increased to 1.6 +/- 0.5 pmol/mg (p less than 0.01; n = 14). Simultaneously, the platelet recovery (measured over 20 seconds after injection) was enhanced (by 45 +/- 11%; p less than 0.01) during endothelial stimulation with acetylcholine. Treatment with the EDRF inhibitor hemoglobin (6 microM) completely abolished the increase in platelet cGMP (p less than 0.01; n = 11) as well as the enhanced platelet recovery (n = 8). Inhibition of EDRF by hemoglobin reduced also the basal platelet cGMP content to 0.17 +/- 0.11 pmol/mg (p less than 0.01). The data indicate that basally released EDRF is able to increase cGMP in platelets during a single passage through the coronary bed. The enhanced recovery of platelets after EDRF stimulation, which coincides with an increase of platelet cGMP, suggests that EDRF plays an important role as inhibitor of platelet activation in the coronary circulation.
‘I am in blood Stepp'd in so far…’: ethical dilemmas and the sports team doctor
Authors: Brian Meldan Devitt, Conor McCarthy
Journal: British Journal of Sports Medicine (2009)

There are many ethical dilemmas that are unique to sports medicine because of the unusual clinical environment of caring for players within the context of a team whose primary objective is to win. Many of these ethical issues arise because the traditional relationship between doctor and patient is distorted or absent. The emergence of a doctor–patient–team triad has created a scenario in which the team’s priority can conflict with or even replace the doctor’s primary obligation to player well-being. As a result, the customary ethical norms that provide guidelines for most forms of clinical practice, such as patient autonomy and confidentiality, are not easily translated in the field of sports medicine. Sports doctors are frequently under intense pressure, whether implicit or explicit, from management, coaches, trainers and agents, to improve performance of the athlete in the short term rather than considering the long-term sequelae of such decisions. A myriad of ethical dilemmas are encountered, and for many of these dilemmas there are no right answers. In this article, a number of ethical principles and how they relate to sports medicine are discussed. To conclude, a list of guidelines has been drawn up to offer some support to doctors facing an ethical quandary, the most important of which is ‘do not abdicate your responsibility to the individual player.’ ‘I am in blood Stepp’d in so far that, should I wade no more, Returning would be as tedious as to go o’er’ —Macbeth: Act III, Scene IV, William Shakespeare
Ancestral Alleles and Population Origins: Inferences Depend on Mutation Rate
Authors: A. R. Rogers, S. Wooding, C. D. Huff, M. A. Batzer, L. B. Jorde
Journal: Molecular Biology and Evolution (2007)

Previous studies have found that at most human loci, ancestral alleles are "African," in the sense that they reach their highest frequency there. Conventional wisdom holds that this reflects a recent African origin of modern humans. This paper challenges that view by showing that the empirical pattern (of elevated allele frequencies within Africa) is not as pervasive as has been thought. We confirm this African bias in a set of mainly protein-coding loci, but find a smaller bias in Alu insertion polymorphisms, and an even smaller bias in noncoding loci. Thus, the strong bias that was originally observed must reflect some factor that varies among data sets—something other than population history. This factor may be the per-locus mutation rate: the African bias is most pronounced in loci where this rate is high. The distribution of ancestral alleles among populations has been studied using 2 methods. One of these involves comparing the fractions of loci that reach maximal frequency in each population. The other compares the average frequencies of ancestral alleles. The first of these methods reflects history in a manner that depends on the mutation rate. When that rate is high, ancestral alleles at most loci reach their highest frequency in the ancestral population. When that rate is low, the reverse is true. The other method—comparing averages—is unresponsive. Average ancestral allele frequencies are affected neither by mutation rate nor by the history of population size and migration. In the absence of selection and ascertainment bias, they should be the same everywhere. This is true of one data set, but not of 2 others. This also suggests the action of some factor, such as selection or ascertainment bias, that varies among data sets.
Effectiveness of Screening With Annual Magnetic Resonance Imaging and Mammography: Results of the Initial Screen From the Ontario High Risk Breast Screening Program
Authors: Anna M. Chiarelli, Maegan V. Prummel, Derek Muradali, Vicky Majpruz, Meaghan Horgan, June C. Carroll, Andrea Eisen, Wendy S. Meschino, Rene S. Shumak, Ellen Warner, Linda Rabeneck
Journal: Journal of Clinical Oncology (2014)

The Ontario Breast Screening Program expanded in July 2011 to screen women age 30 to 69 years at high risk for breast cancer with annual magnetic resonance imaging (MRI) and digital mammography. To the best of our knowledge, this is the first organized screening program for women at high risk for breast cancer.Performance measures after assessment were compared with screening results for 2,207 women with initial screening examinations. The following criteria were used to determine eligibility: known mutation in BRCA1, BRCA2, or other gene predisposing to a markedly increased risk of breast cancer, untested first-degree relative of a gene mutation carrier, family history consistent with hereditary breast cancer syndrome and estimated personal lifetime breast cancer risk ≥ 25%, or radiation therapy to the chest (before age 30 years and at least 8 years previously).The recall rate was significantly higher among women who had abnormal MRI alone (15.1%; 95% CI, 13.8% to 16.4%) compared with mammogram alone (6.4%; 95% CI, 5.5% to 7.3%). Of the 35 breast cancers detected (16.3 per 1,000; 95% CI, 11.2 to 22.2), none were detected by mammogram alone, 23 (65.7%) were detected by MRI alone (10.7 per 1,000; 95% CI, 6.7 to 15.8), and 25 (71%) were detected among women who were known gene mutation carriers (30.8 per 1,000, 95% CI, 19.4 to 43.7). The positive predictive value was highest for detection based on mammogram and MRI (12.4%; 95% CI, 7.3% to 19.3%).Screening with annual MRI combined with mammography has the potential to be effectively implemented into an organized breast screening program for women at high risk for breast cancer. This could be considered an important management option for known BRCA gene mutation carriers.
Hepatic Enzymes, the Metabolic Syndrome, and the Risk of Type 2 Diabetes in Older Men
Authors: Sasiwarang Goya Wannamethee, Andrew Gerald Shaper, Lucy Lennon, Peter H. Whincup
Journal: Diabetes Care (2005)

OBJECTIVE—We have examined the relationship between hepatic enzymes, the metabolic syndrome, insulin resistance, and type 2 diabetes and assessed the potential of hepatic enzyme measurements in determining diabetes risk. RESEARCH DESIGN AND METHODS—We conducted a prospective study of 3,500 nondiabetic men aged 60–79 years who were followed-up for a mean period of 5 years and in whom there were 100 incident type 2 diabetes cases. RESULTS—In cross-sectional analyses, alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) were strongly associated with obesity, insulin resistance, and the metabolic syndrome. Prospectively, the risk of type 2 diabetes significantly increased with increasing levels of ALT and GGT even after adjustment for confounders including BMI (top versus bottom quarter ALT: relative risk 2.72 [95% CI 1.47–5.02]; GGT: 3.68 [1.68–8.04]). Additional adjustment for insulin resistance attenuated the effects, but the relationships with ALT and GGT remained significant (1.91 [1.01–3.60] and 2.69 [1.21–5.97], respectively). Further adjustment for inflammatory markers (C-reactive protein) made minor differences. Among high-risk subjects (obese men or those with the metabolic syndrome), elevated GGT and ALT enhanced the prediction of diabetes risk. CONCLUSIONS— Elevated levels of ALT and GGT within the normal range are independent predictors of type 2 diabetes in older men and are useful additional measures in identifying those at high risk of diabetes.
Endogenous IL-13 Limits Humoral Responses and Injury in Experimental Glomerulonephritis but Does Not Regulate Th1 Cell-Mediated Crescentic Glomerulonephritis
Authors: A. Richard Kitching, Amanda L. Turner, Gabriella R.A. Wilson, Kristy L. Edgtton, Peter G. Tipping, Stephen R. Holdsworth
Journal: Journal of the American Society of Nephrology (2004)

IL-13 is produced by T helper 2 (Th2) cells, has a role in stimulating Th2-mediated injury, alters humoral responses, and may directly suppress macrophage and neutrophil function. In immune renal disease, the engagement of different effector mediator systems, including humoral and cell-mediated effectors, can result in glomerular injury. Experimental crescentic glomerulonephritis (known as autologous anti–glomerular basement membrane glomerulonephritis) induced by planting an antigen in glomeruli of mice is Th1 directed, delayed-type hypersensitivity (DTH)-like, and antibody independent. To test the hypothesis that, like the counterregulatory Th2 cytokines IL-4 and IL-10, endogenous IL-13 limits effector Th1 responses in glomerulonephritis, crescentic glomerulonephritis was induced in IL-13+/+ and IL-13−/− mice. Although IL-13−/− mice developed increased serum antigen–specific antibody levels, increased glomerular antibody deposition and enhanced switching to the Th1-associated IgG2a subclass, they developed a similar degree of crescentic glomerulonephritis, with similar glomerular T cell/macrophage numbers, renal impairment, and proteinuria. Antigen-specific dermal DTH and IFN-γ production by antigen-stimulated splenocytes was unaltered. In immune complex (apoferritin-induced) glomerulonephritis, where renal injury is humorally mediated, IL-13−/− mice developed enhanced humoral immune responses and increased proteinuria, with increased IgG2a responses, a more peripheral distribution of immune complexes, but no alterations in leukocyte recruitment. These results demonstrate dissociation of IL-13's effects in antigen induced renal disease with little effect on cellular responses but suppressive effects on humoral effectors and switching to IgG2a. They indicate a role for IL-13 in limiting antibody-mediated renal injury, but not in regulating DTH-like cell-mediated responses in the kidney.
Smoking cessation: integrating recent advances into clinical practice
Authors: T Coleman
Journal: Thorax (2001)

Smoking remains a prevalent habit with serious consequences for public health.There are now eVective treatments for nicotine addiction and, in the UK, specialist services for the treatment of smoking cessation are becoming available in all areas.This paper reviews the role of treatments for nicotine addiction in the management of smoking cessation.Recommendations are made for the judicious use of these therapies and also for the rational use of the new UK smoking cessation services.
Detection and Clinical Importance of Micrometastatic Disease
Authors: K. Pantel, R. J. Cote, O. Fodstad
Journal: JNCI Journal of the National Cancer Institute (1999)

Metastatic relapse in patients with solid tumors is caused by systemic preoperative or perioperative dissemination of tumor cells. The presence of individual tumor cells in bone marrow and in peripheral blood can be detected by immunologic or molecular methods and is being regarded increasingly as a clinically relevant prognostic factor. Because the goal of adjuvant therapy is the eradication of occult micrometastatic tumor cells before metastatic disease becomes clinically evident, the early detection of micrometastases could identify the patients who are most (and least) likely to benefit from adjuvant therapy. In addition, more sensitive methods for detecting such cells should increase knowledge about the biologic mechanisms of metastasis and improve the diagnosis and treatment of micrometastatic disease. In contrast to solid metastatic tumors, micrometastatic tumor cells are appropriate targets for intravenously applied agents because macromolecules and immunocompetent effector cells should have access to the tumor cells. Because the majority of micrometastatic tumor cells may be nonproliferative (G 0 phase), standard cytotoxic chemotherapies aimed at proliferating cells may be less effective, which might explain, in part, the failure of chemotherapy. Thus, adjuvant therapies that are aimed at dividing and quiescent cells, such as antibody-based therapies, are of considerable interest. From a literature search that used the databases MEDLINE®, CANCERLIT®, Biosis®, Embase®, and SciSearch®, we discuss the current state of research on minimal residual cancer in patients with epithelial tumors and the diagnostic and clinical implications of these findings.
Bortezomib Inhibits Cell-Cell Adhesion and Cell Migration and Enhances Epidermal Growth Factor Receptor Inhibitor–Induced Cell Death in Squamous Cell Cancer
Authors: Jochen H. Lorch, Tarita O. Thomas, Hans-Joachim Schmoll
Journal: Cancer Research (2007)

Abstract The lack of cell-cell adhesion and increased migration are key characteristics of cancer cells. The loss of expression of cell adhesion components and overexpression of components critical for cell migration, such as focal adhesion kinase (FAK), correlate with poor prognosis. Because alteration of protein turnover affects the expression levels and, in turn, may influence protein function, we investigated the effects of the proteasome inhibitor bortezomib on cell adhesion and migration in oral squamous cell cancer cell lines SCC68 and SCC15. Following treatment with bortezomib, protein levels of adherens junction components such as E-cadherin were unchanged. The desmosomal linker protein desmoplakin level was increased, whereas the protein level of the desmosomal cadherin, desmoglein 2, was diminished. Reduced desmoglein 2 levels correlated with the diminished strength of mechanical cell-cell adhesion. The protein level of the epidermal growth factor receptor (EGFR) increased after proteasome inhibition and EGFR inhibition with the EGFR-specific tyrosine kinase inhibitor PKI166 was able to restore cell-cell adhesion. Furthermore, we found that the combination of PKI166 with bortezomib enhanced the rate of cell death. Although the FAK protein level was unchanged following bortezomib treatment, recruitment of FAK phosphorylated at tyrosine residue 397 to the periphery of the cell was induced. Migration was reduced following treatment with bortezomib, which could potentially be explained by a prominent but disorganized actin fiber network revealed through immunofluorescence. Collectively, our results suggest that proteasome inhibition using bortezomib affects cell adhesion and cell migration profoundly and provides a rationale for its clinical use in conjunction with an EGFR inhibitor. [Cancer Res 2007;67(2):727–34]
Government drops plans to extend smoking ban in England
Authors: A. O'Dowd
Journal: BMJ (2010)

The UK government has dropped a planned review of England’s smoking legislation that might have extended the ban on smoking in public places.

The Department of Health made it clear this week that a scheduled three year review of England’s law, introduced in July 2007 to make virtually all enclosed public places and workplaces in England smoke free, has been shelved.

Specialists in the field have expressed their disappointment at the decision, saying they had hoped that the government would go further and extend smoke-free legislation to include public places frequented by children and to prohibit all smoking in cars and other vehicles.

The public health minister, …