tbuckley/cabot-search huggingface dataset:
Compensated cardiac hypertrophy: arrhythmogenicity and the new myocardial phenotype. I. Fibrosis
Authors: P Assayag
Journal: Cardiovascular Research (1997)

The high incidence of arrhythmias in compensated cardiac hypertrophy is related to two independently regulated components—fibrosis and the adaptational phenotypic changes in membrane proteins linked to cardiac hypertrophy, and fibrosis. During the regression of hypertensive cardiopathy in middle-aged spontaneously hypertensive rats, the roles of cardiac hypertrophy and fibrosis can be analysed separately, revealing that both correlate independently with arrhythmias. In an experimental model of myocardial infarction it is possible to prevent arrhythmias with propranolol at the same time as cardiac hypertrophy, despite ventricular fibrosis. Fibrosis would appear to create arrhythmias both by anatomical uncoupling and by a re-entry mechanism generated by the zig-zag propagation of the transverse waveform. Triggered activity and automaticity depend on the membrane phenotype of the cardiocyte. They also play an important role, which is aggravated by myocardial heterogeneity.
From an Ethics of Rationing to an Ethics of Waste Avoidance
Authors: Howard Brody
Journal: New England Journal of Medicine (2012)

Interview with Dr. Howard Brody on the ethics of rationing and waste avoidance in health care. (24:30)Download Waste in U.S. health care — spending on interventions that don't benefit patients — amounts to at least 30% of health care spending and is a major driver of cost increases. So the ethical debate about cost containment is shifting focus from rationing to waste avoidance.
Does plasma cholesterol concentration predict mortality from coronary heart disease in elderly people? 18 year follow up in Whitehall study.
Authors: M J Shipley, S J Pocock, M G Marmot
Journal: BMJ (1991)

OBJECTIVE--To explore the extent to which the relation between plasma cholesterol concentration and risk of death from coronary heart disease in men persists into old age. DESIGN--18 year follow up of male Whitehall civil servants. Plasma cholesterol concentrations and other risk factors were determined at first examination in 1967-9 when they were aged 40-69. Death of men up to 31 January 1987 was recorded. SUBJECTS--18,296 male civil servants, 4155 of whom died during follow up. MAIN OUTCOME MEASURES--Cause and age of death. Cholesterol concentration in 1967-9 and number of years elapsed between testing and death. RESULTS--1676 men died of coronary heart disease. The mean cholesterol concentration in these men was 0.32 mmol/l higher than that in all other men (95% confidence interval 0.26 to 0.37 mmol/l). This difference in cholesterol concentrations fell 0.15 mmol/l with every 10 years9 increase in age at screening. The risk of raised cholesterol concentration fell with age at death. Compared with other men cholesterol concentration in those who died of coronary heart disease was 0.44 mmol/l higher in those who died aged less than 60 and 0.26 mmol/l higher in those aged 60-79 (p = 0.03). For a given age at death the longer the gap between cholesterol measurement and death the more predictive the cholesterol concentration, both for coronary heart disease and all cause mortality (trend test p = 0.06 and 0.03 respectively). CONCLUSION--Reducing plasma cholesterol concentrations in middle age may influence the risk of death from coronary heart disease in old age.
Title: Relation Of Early Life Regulatory T-cell Function And Phenotype Development To Wheeze And Allergy: The Urban Environment And Childhood Asthma
Authors: R.M. McLoughlin, N.P. Ly, C.M. Visness, P.K. Wallace, W.W. Cruikshank, B. Ruiz-Perez, J.E. Gern, D.R. Gold
Journal: Journal of Allergy and Clinical Immunology (2009)
Increased immunoreactivity of stromal cell-derived factor‐1 and angiogenesis in asthma
Authors: M. Hoshino, N. Aoike, M. Takahashi, Y. Nakamura, T. Nakagawa
Journal: European Respiratory Journal (2003)

Stromal cell-derived factor-1 (SDF-1) acts as a chemoattractant for leukocytes and can induce neovascularisation. To examine the role of SDF-1 in the development of angiogenesis, immunohistochemical studies were performed on bronchial biopsy specimens from asthmatic and control subjects. Bronchial biopsy specimens were obtained from 13 asthmatic and eight control subjects. The number of vessels and the percentage area they occupied were estimated after staining for type-IV collagen. In addition the number of SDF-1-positive cells was determined. There was a significant increase in the number of vessels and the percentage vascularity in the submucosa of asthmatic subjects compared with control subjects. Asthmatic subjects exhibited a greater number of SDF-1-positive cells in the airway mucosa than control subjects. The degree of vascularity was associated with the number of SDF-1-positive cells. Furthermore, the number of SDF-1-positive cells was inversely correlated with airway calibre and airway hyperresponsiveness. Colocalisation studies revealed that endothelial cells, macrophages and T-lymphocytes were the major sources of SDF-1. These findings suggest that increased vascularity of bronchial mucosa in asthmatic subjects is closely related to the expression of stromal cell-derived factor-1 positive cells, which may play a role in remodelling of airways via angiogenesis.
French parliamentary committee advocates passive euthanasia
Authors: Jane Burgermeister
Journal: BMJ (2004)

Doctors' associations in France have welcomed a report by a parliamentary committee recommending that passive euthanasia should be allowed.

In a landmark report, the cross party committee of 31 deputies recommended that terminally ill patients should be given the right to refuse treatment in certain circumstances. The committee said, however, that active euthanasia—that is, when a doctor acts deliberately to cause a patient's death—should not be legalised.

The health minister, Philippe Douste-Blazy, said that the government was ready to accept the committee's recommendations and give terminally ill patients a greater right …
Attempted passive transfer of a serum factor in chronic urticaria from human to monkey
Authors: C.E.H. Grattan, R.K. Winkelmann, P.E. Zollman
Journal: British Journal of Dermatology (1989)

Journal Article Attempted passive transfer of a serum factor in chronic urticaria from human to monkey Get access C.E.H. Grattan, C.E.H. Grattan Department of Dermatology, The General Hospital, Birmingham, U.K. Search for other works by this author on: Oxford Academic Google Scholar R.K. Winkelmann, R.K. Winkelmann Dermatology Department, Mayo Clinic, Rochester, Minnesota, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar P.E. Zollman P.E. Zollman Dermatology Department, Mayo Clinic, Rochester, Minnesota, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 120, Issue 6, 1 June 1989, Pages 853–856, https://doi.org/10.1111/j.1365-2133.1989.tb01387.x Published: 01 June 1989
Resting heart rate and incident heart failure and cardiovascular mortality in older adults: role of inflammation and endothelial dysfunction: the PROSPER study
Authors: David Nanchen, David J. Stott, Jacobijn Gussekloo, Simon P. Mooijaart, Rudi G.J. Westendorp, J. Wouter Jukema, Peter W. Macfarlane, Jacques Cornuz, Nicolas Rodondi, Brendan M. Buckley, Ian Ford, Naveed Sattar, Anton J.M. de Craen
Journal: European Journal of Heart Failure (2012)
The mechanism of the natriuresis of fasting.
Authors: M H Sigler
Journal: Journal of Clinical Investigation (1975)

This study tests the hypothesis than obligatory cation coverage of metabolicaly generated anions is the mechanism for the sodium diuresis of fasting. Nine obese female subjects were equilibrated on a constant sodium and caloric intake and then fasted while sodium intake was maintianed. Particular activity schedule during fasting as during control. Consecutive 3-h increases in urinary sodium , ammonium, and potassium excretion during fasting were matched against simultaneously determined increases in organic acid anions (OAS) and H2PO4 minus, which would exist in combination with the cations. The changes were significantly correlated (r equals 0.891, P less than 0.001) in the relationship y equals 0.73x plus 19 where y equals increases in organic acid salts plus H2POJ minus and x equals increases in cations. As ammonium excretion rose, sodium conservation occurred with ammonium replacing sodium at the major urinary cation. Corollaries to the hypothesis were also found to be true. They were: (a) Increases in ammonium excretion lagged considerably behind increases in OAS plus H2PO4 minus during the diuretic phase making sodium coverage necessary. (b) Sodium loss was much greater than chloride although chloride balance was minimally negative. (c) After refeeding with glucose, sodium excretion promptly decreased and appeared best correlated with simultaneous decreases in OAS. Ammonium excretion also fell but much less than sodium. The data support the hypothesis that obligatory cation coverage of metabolically generated aniuns is a major mechanism responsible for the sodium diuresis of fasting.
Abstract 5336: Mathematical models for cellular response to radiochemotherapy
Authors: Katherine S. Williams, Ardith W. El-Kareh, Timothy W. Secomb
Journal: Cancer Research (2014)

Abstract To optimize radiochemotherapy, several clinically adjustable factors must be considered: sequence order (drug administered before, during, or after radiation exposure); time interval between the agents; dose of each agent; and fractionation. Because the combined effects of all these factors are complex, mathematical modeling can provide a useful framework for discerning the role of each individual factor and can be applied to predict response to future experimental protocols. To date, there has been scant effort devoted to mathematical models for cellular response to radiochemotherapy. One widely-used model is based on the assumption that the two modalities act completely independently; the total cell survival fraction is the product of survival fractions for each agent acting alone. However, an examination of a number of dose-response data sets for paclitaxel followed by radiation exposure shows that the independent cell kill model consistently underestimates cell kill. The additive damage model, which is based on the assumption that cell kill depends on a quantity called cellular damage, is constructed as the sum of terms from each agent and is shown to better describe some data sets for ascorbate and paclitaxel. Cellular dose-response data sets for radiochemotherapy have shown complex interactions between therapies, with strong dose-dependent antagonism in some cases, and significant, non-monotonic dependence on the time interval between the modalities in others. We present generalizations of the additive damage model, which include either dose-dependent cell-cycle blocking or transport kinetics, and show that they can describe some of these experimentally-observed complex behaviors. In conclusion, the generalized additive damage model is a promising tool to describe cellular pharmacodynamics of radiochemotherapy and is expected to have application to the optimization of dosage and schedule. Citation Format: Katherine S. Williams, Ardith W. El-Kareh, Timothy W. Secomb. Mathematical models for cellular response to radiochemotherapy. [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 5336. doi:10.1158/1538-7445.AM2014-5336
One of world's poorest countries makes "remarkable" progress on tropical diseases, report says
Authors: A. Gulland
Journal: BMJ (2014)

Sierra Leone’s “rapid achievements” in tackling neglected tropical diseases are “nothing short of remarkable,” concludes a report from the Overseas Development Institute, a UK independent think tank on international development and humanitarian issues.1

Despite being one of the poorest countries in the world and undergoing a brutal civil war from 1991 to 2002, Sierra Leone has seen a 60% decrease in the incidence of onchocerciasis (river blindness) between 2007 and 2009, a 90% decrease in the number of cases of lymphatic filariasis (elephantiasis) between 2007 and 2011, and a 66% decrease in the incidence of schistosomiasis (snail fever) between 2009 and 2012.

Sierra Leone is doing much better than its richer neighbours, …
Acral lentiginous melanoma: conventional histology vs. three-dimensional histology
Authors: V. Lichte, H. Breuninger, G. Metzler, H.M. Haefner, M. Moehrle
Journal: British Journal of Dermatology (2008)

Background Patients with acral lentiginous melanoma (ALM) seem to have a poor prognosis. ALMs represent 4–10% of cutaneous melanomas in white populations. Surgery is mostly based on conventional histological evaluation. With micrographic surgery, continuously spreading tumours can be excised with smaller excision margins for better cosmesis and function. Objectives Clinical parameters and surgical strategies influencing the prognosis of patients with ALM were evaluated. Methods Two hundred and forty-one patients (44% male, 56% female) with stage I/II ALM were recorded during 1980–2006. One hundred and thirty-three patients underwent complete histology of three-dimensional excision margins (3D histology) using the paraffin technique. Risk factors for disease-specific and recurrence-free survival were estimated. Results Patients were aged 26–87 years (median 63) with median tumour thickness of 2·0 mm. The median follow-up was 41 months. Multivariate analysis identified ulceration, conventional histology and tumour thickness as risk factors for recurrence-free and disease-specific survival. Using 3D histology, excision margins were significantly smaller (median 7 vs. 20 mm) without an increased risk of local recurrences. Patients with 3D histology had a 5-year survival of 81% compared with 63% with conventional histology. Retrospective analysis with immunohistological methods (anti-Melan-A) could improve the diagnostic specificity in detecting further melanocytic cell nests. Conclusions Clinical and surgical risk factors seem to have different influences on the outcome of ALM. 3D histology allows reduction of excision margins by two-thirds without an increased risk of local recurrences and with better prognosis. 3D immunohistology could be a valuable diagnostic tool to reduce the rate of local recurrences.
School Examinations Enhance Airway Inflammation to Antigen Challenge
Authors: Lin Ying Liu, Christopher L. Coe, Cheri A. Swenson, Elizabeth A. Kelly, Hirohito Kita, William W. Busse
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Psychological stress can lead to asthma exacerbations in some patients. It is our hypothesis that the stress effect can occur through an enhancement of allergic inflammatory response. To investigate this possibility, airway antigen challenge was evaluated in 20 college students with mild asthma during both a low-stress phase (midsemester or two weeks postfinal examination) and a stress phase (final examination week). Subjects completed questionnaires to assess psychological state and underwent inhaled antigen challenge. Sputum samples were collected before challenge, and six and 24 hours and seven days postchallenge. Leukocytes were counted and eosinophil-derived neurotoxin (EDN) was measured in sputum supernates. Sputum cells were cultured and stimulated ex vivo with phytohemagglutinin (10 μ g/ml), and culture supernates were assayed for interleukin-5 (IL-5) and interferon- γ by enzyme-linked immunosorbent assay. Sputum eosinophils and EDN levels significantly increased at six and 24 hours postchallenge and were enhanced during the stress phase (p < 0.01). IL-5 generation by sputum cells was also increased at 24 hours during stress and correlated with airway eosinophils (rs = 0.65, p < 0.05). Students' anxiety and depression scores were significantly higher during the examination period. Our findings suggest that stress associated with final examinations can act as a cofactor to increase eosinophilic airway inflammation to antigen challenge and thus may enhance asthma severity.
Abstract 3992: Proteomic profiling of breast tumors using a microfluidic quantitative immunohistochemistry platform
Authors: Minseok S. Kim, Seyong Kwon, Jungmin Lee, Eun-Sook Lee, Je-Kyun Park
Journal: Cancer Research (2010)

Abstract In breast cancers, one of the most troublesome characteristics for cure is the heterogeneity in point of genetic alterations, treatment-response variability, and histopathological features. This characteristic urgently requires personalized tailored therapy, getting out of a simple and widespread prescription. Therefore, the investigation of multiple biomarkers is inevitable for complete recovery. Immunohistochemistry (IHC) has been a major diagnostic method in various malignancies and many studies showing the relationship between immunohistochemical profiles and molecular classification support that IHC might play a significant role in subclassification of breast cancer patients for personalized medicine. However, conventional IHC method is not adequate for examination of multiple biomarkers since it requires consumption of many tissue slices and proportionally increases diagnostic cost which can give a big burden to patients. In addition, subjective decision for biomarker expression is another major problem. Therefore, an innovative multiplexed IHC platform satisfying not only investigation of multiple biomarkers with reducing consumption of tissue slice but also quantification for the biomarkers is the current demand for personalized medicine. Here, a novel microfluidic multiplexed and quantitative IHC platform was developed for proteomic profiling of breast tumors. The large-scale microfluidic device was designed to have 20 microchannels, and multilayer soft lithography and two-step lithography technologies were used for fabrication. Fluidic resistance was considered for equivalent flow rate of individual reaction channel. Ten biomarkers known as predictive and prognostic indicators in breast cancers, including SMM-HC, CK5, CK14, E-Cadherin, p53, ER, p63, PR, HER2, and Ki-67, were examined on four breast cancer cell lines (MCF-7, SK-BR-3, AU-565, and HCC70) to confirm the massive multiplexed IHC. Results showed that the platform successfully realized the expressions of each biomarker on a cellblock at the same time and proteomic profiling for 10 biomarkers could be quantitatively analyzed from the image analysis. The platform was also applied to a breast cancer tissue sample and the result was corresponded to the results of conventional IHC method. This microfluidic platform is expected to realize precise subtyping of cancer patients by the proteomic profiling even though the size of tumor samples acquired by operation has been getting smaller due to early detection and neoadjuvant therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3992.
Abstract P2-10-42: Gene expression profiling to predict the risk of locoregional recurrence in breast cancer
Authors: CA Drukker, MV Nijenhuis, SG Elias, J Wesseling, NS Russell, F de Snoo, LJ van't Veer, PD Beitsch, EJT Rutgers
Journal: Cancer Research (2012)

Abstract Background The 70-gene signature (Mammaprint™) has been developed to predict the risk of distant metastases in breast cancer and select those patients who will have benefit in survival from adjuvant treatment. Aside from distant metastases, the development of locoregional recurrence is a significant predictor of survival. Given the strong association between locoregional recurrence and distant recurrence, we hypothesize that the 70-gene signature will be predictive of locoregional recurrence as well. Methods We updated follow-up and radiotherapy details for all 1053 unique breast cancer patients treated at the NKI-AVL who previously participated in various 70-gene signature validation studies. Diagnosis was between 1984 and 2006. All patients were primarily treated surgically with either breast-conservation therapy or mastectomy. Adjuvant treatment consisted of radiotherapy, chemotherapy and/or endocrine therapy as indicated. Known risk factors for locoregional recurrence including age, tumor free resection margins, tumor size, grade, ER status, Her2 status, nodal irradiation and tumor bed boost were included in our analysis in addition to the 70-gene signature result. Results Through 10 years of follow-up, 80 locoregional recurrences occurred. Patients with a 70-gene signature high risk result (n = 492) had a locoregional recurrence risk of 8.8% (95%CI: 6.3–11.3) at 5 years and 13.5 % (95%CI: 10.2–16.8) at 10 years, which was 2.6% (95%CI: 1.2–4.0) at 5 years and 5.7% (95%CI:3.5–7.9) at 10 years for patients with a low risk 70-gene signature (n = 561)(Logrank: p &amp;lt; 0.0001). Accordingly, patients with a high risk 70-gene signature had an approximately 3 times higher risk of locoregional recurrence than patients with a low risk 70-gene signature (univariable hazard ratio (HR) 2.89; 95%CI: 1.80–4.63). Adding the 70-gene signature to a Cox proportional hazard model containing age, size, grade, ER status, involvement of axillary lymph nodes, surgical treatment and adjuvant treatment (radiotherapy, chemotherapy and/or endocrine therapy), significantly improved the model (likelihood ratio: p = 0.007). In that model, the multivariable HR for high versus low 70-gene signature risk was 2.27 (95%CI: 1.24–4.15). Conclusion The 70-gene signature is able to predict the risk of locoregional recurrence, independent of known risk factors. Using the 70-gene signature may help in selecting those patients who will benefit from extensive adjuvant treatment. Additionally, the 70-gene signature may also select a group of patients at a low risk of locoregional recurrence who may be cured with limited local treatment alone. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-42.