tbuckley/cabot-search huggingface dataset:
Bioethics Advisory Commission Holds First Meeting to Define Governing Principles of Ethical Research
Authors: Charles Marwick
Journal: JAMA (1996)

ENSURING BETTER protection for human subjects who participate in biomedical and behavioral research and determining the appropriate use of genetic testing were 2 charges to the National Bioethics Advisory Commission at its inaugural meeting. The 18-member group met early last month at the National Institutes of Health (NIH) in Bethesda, Md, a year after President Clinton ordered its creation. Officially, the commission terminates in October 1997. But, said its chair, Harold T. Shapiro, PhD, "We're behaving as if the commission will go on for 4 or 5 years. Certainly we are designing our work for a longer horizon than 1 year." Shapiro is president of Princeton University, Princeton, NJ. <h3>Recommendations Requested</h3> The development of recommendations to ensure the well-being, autonomy, and privacy of human subjects undergoing experimental treatment, as well as recommendations for the appropriate use of genetic information, was requested of the 17-member commission by John H. Gibbons,
Are Physicians' Office Laboratory Results of Comparable Quality to Those Produced in Other Laboratory Settings?
Authors: Jerry Hurst
Journal: JAMA (1998)

Context.—In 1995, California adopted a bill that brought laboratory laws in line with the 1988 Clinical Laboratory Improvement Amendments' standards for clinical laboratories and mandated a study comparing results in physicians' office laboratories (POLs) with other settings.Objective.—To determine whether persons conducting tests in POLs produce accurate and reliable test results comparable to those produced by non-POLs.Design.—Survey of clinical laboratories using proficiency testing data.Setting.—All California clinical laboratories participating in the American Association of Bioanalysts proficiency testing program in 1996 (n=1110).Main Outcome Measures.—"Unsatisfactory" (single testing event failure) and "unsuccessful" (repeated testing event failure) on proficiency testing samples.Results.—The unsatisfactory failure rate for POLs was nearly 3 times (21.5% vs 8.1%) the rate for the non-POLs and about 1.5 times (21.5% vs 14.0%) for POLs that used laboratory professionals as testing or supervisory personnel (P&lt;.001). The POL unsuccessful rate was more than 4 times (4.4% vs 0.9%) the rate for non-POLs and more than twice (4.4% vs 1.8%) the rate for the POLs using laboratory professionals (P&lt;.001).Conclusions.—Significant differences exist among POLs, POLs using licensed clinical laboratory scientists (medical technologists), and non-POLs. Testing personnel in many POLs might lack the necessary education, training, and oversight common to larger facilities. We must better understand the contributing factors that result in the poorer results of POLs relative to non-POLs. In the meantime, patients should be aware that preliminary findings suggest that differences in quality of laboratory tests based on testing site may exist. Laboratory directors at all testing sites must ensure that they understand laboratory practice sufficiently to minimize errors and maximize accuracy and reliability. Directors must understand their obligation when they elect to oversee those assigned testing responsibility. Legislators may wish to reconsider the wisdom of further easing restrictions on those to whom we entrust our laboratory specimens.
Lateral Subcutaneous Internal Sphincterotomy in Treatment of Anal Fissure
Authors: D. C. Hoffmann, J. C. Goligher
Journal: BMJ (1970)

One hundred and three patients with anal fissures have been treated by lateral internal sphincterotomy performed by a subcutaneous myotomy technique, and 99 have been successfully followed up for from 3 to 24 months (mean 11 months). The operation was free from significant complications, apart from slight reactionary bleeding in one case and a perianal abscess in another. The fissure persisted or recurred in three cases, in one of which a further lateral sphincterotomy was performed, with cure. Various minor defects of anal continence were noted in 12 cases. These results have been found to be superior to those obtained previously in the same surgical unit with open posterior internal sphincterotomy and simple sphincter-stretching respectively in the treatment of anal fissure. The most reliable and satisfactory operation at present available for this condition seems, therefore, to be lateral subcutaneous internal sphincterotomy.
Greed and the medical profession.
Authors: R. Crawshaw
Journal: BMJ (1993)

O rganised medicine is not giving proper attention to the disturbing presence in the profession of a universal human trait: greed.Perhaps doctors' greed is less of a problem in Britain where an estimated 70% of the doctors are generalists, and reimbursement in the main is controlled by the national health system.Not so in the United States where 70% of doctors are specialists and an open health care market allows doctors to charge "reasonable and customary" fees.This is interpreted by some as "all the traffic will bear."Despite considerable evidence at the other end of the generosity scale that 64% of US
The effect of peritoneovenous shunting on catecholamine metabolism in patients with hepatic ascites
Authors: Laurence M. Blendis, Michael J. Sole, Peter Campbell, Alan G. Lossing, Paul D. Greig, Bryce R. Taylor, Bernard Langer
Journal: Hepatology (1987)

The elevated catecholamine levels in cirrhotic patients with ascites have been proposed to be due to sympathetic overactivity secondary either to reduced intravascular volume or to an underlying cardiovascular abnormality such as reduced pressor responsiveness. Furthermore, these elevated catecholamine levels have been proposed to be involved in the pathogenesis of salt and water retention. Therefore, the effect of peritoneovenous shunting on the circulating levels and renal excretion of catecholamines were studied in six patients with massive refractive ascites preoperative within the first 8 hr postoperative and by 2 weeks postoperative under metabolic conditions. The recirculation of ascites into the intravascular compartment resulted perioperatively in significant rises in cardiac output (p = 0.001), para-amino-hippurate clearance (p = 0.08), creatinine clearance, diuresis (p = 0.05) and natriuresis (p = 0.06). Systemic blood pressure remained unchanged while systemic vascular resistance decreased (p less than 0.05). Preoperative circulating levels of free catecholamine were highly elevated, and renal vein concentrations were about 25% higher than renal arterial levels. Perioperatively, there was little change in circulating catecholamine levels or distribution of renal blood flow although renal artery and vein concentrations tended to equalize. In contrast by 2 weeks postoperatively, free catecholamine levels had fallen to within the normal ranges: mean norepinephrine from 1,477.6 +/- 194.6 to 395 +/- 62.9 pg per ml (p less than 0.05); epinephrine from 276 +/- 74.2 to 65.7 +/- 15.0 pg per ml (p less than 0.02), and dopamine from 325.6 +/- 175.2 to 47.9 +/- 5.3 pg per ml.(ABSTRACT TRUNCATED AT 250 WORDS)
Quantitative Magnetic Resonance Imaging Parameters and Their Relationship to Mammographic Pattern
Authors: C. S. Poon, M. J. Bronskill, R. M. Henkelman, N. F. Boyd
Journal: JNCI Journal of the National Cancer Institute (1992)

Breast cancer exhibits wide international variation in incidence, which has led to the identification of several factors correlating with the risk of the disease. Magnetic resonance imaging (MRI) techniques can provide quantitative information about the biological and physical properties of tissue.This work tested several magnetic resonance tissue parameters for their ability to distinguish quantitatively between breast tissues in subjects at substantially different risk for breast cancer as defined indirectly by their parenchymal pattern on mammograms.Quantitative MRI parameters (relative water content, longitudinal relaxation time [T1], and transverse relaxation time [T2]) were measured for breast tissue using newly developed techniques in two groups of women with mammographic parenchymal appearance associated with high (Dy pattern [i.e., extensive nodular or diffuse density]; n = 12) or low (N1 pattern [i.e., breast containing mainly fat]; n = 11) risk of breast cancer.The two groups have significantly different average relative water content (P less than .0001) and average T1 (P less than .0001). Pixel histograms of T2 values show marked differences between the two groups which can be characterized with a fourth moment parameter.Quantitative MRI techniques exhibit good potential for assessing tissue characteristics in the breast that are associated with risk of breast cancer.Future work will address the direct correlation of MRI parameters with risk of breast cancer.
Fingolimod modulates bad memories
Authors: Charlotte Harrison
Journal: Nature Reviews Drug Discovery (2014)

Clues to metformin's anticancer actionsThe diabetes drug metformin also has anticancer actions, but it is uncertain how these are achieved.This study showed that these effects of metformin are mediated through inhibition of mitochondrial complex 1.In vitro, metformin inhibited the proliferation of cancer cells when glucose was present, but caused cell death in the absence of glucose.Moreover, metformin reduced the hypoxic activation of hypoxia-inducible factor 1. These data suggest that metformin could be a clinically useful adjunct to therapies that limit the availability of glucose and oxygen to tumour cells.
Dr. Ranking's Inquiries: On Cod-Liver Oil in Phthisis
Authors: None Clark
Journal: BMJ (1849)

not of simply presenting petitions, but of taking steps to draw up a short Bill, to which no class in this country could possibly object, and which might, with the sanction of the profession, be easily passed through Parliament in the next se6sion.We earnestly and confidently hope that Dr. Toogood will undertake to carry through the task which he has so well commenced, and that he will be cordially assisted by those members of the Association whom he
Insulin Binding and Insulin Sensitivity in Isolated Growth Hormone Deficiency
Authors: Vijay Soman, William Tamborlane, Ralph DeFronzo, Myron Genel, Philip Felig
Journal: New England Journal of Medicine (1978)

125I-insulin binding to monocytes was examined in five children and one adult with isolated growth hormone deficiency before and after three to 12 weeks of growth hormone treatment, and in eight controls. Before treatment, mean plasma glucose was 15 mg per deciliter below controls, and plasma insulin was reduced by 40 per cent. Insulin binding to monocytes was 70 per cent greater than controls (P<0.005). Insulin-mediated glucose uptake (determined in the adult patient) was 25 per cent greater than mean control levels. After treatment, plasma glucose rose to control levels, plasma insulin increased to 75 per cent above controls (P<0.01), and insulin binding fell to 50 per cent below controls (P<0.01). Insulin-mediated glucose uptake fell to 30 per cent below the mean control rate.
How can HIV be prevented in South Africa? A social perspective
Authors: C. Campbell
Journal: BMJ (2002)

South Africa's lack of government leadership in the fight against HIV and AIDS has resulted in disunity in local HIV/AIDS circles. Catherine Campbell and Yodwa Mzaidume suggest that peer education—with local people taking control of HIV prevention efforts—can be successful but depends on collaboration between many stakeholder groups at local, national, and international level

HIV and AIDS prevention programmes often have little impact because such programmes have traditionally had a biomedical focus and an emphasis on individual behaviour. Yet social and community level factors influence the rate and method of HIV transmission and can affect the success or failure of prevention programmes.

In this paper we discuss the importance of these factors with reference to a South African prevention programme. We argue that HIV prevention efforts are affected by the participation of a wide range of groups and processes at local, national, and international level. The scope of research, interventions, and policies must be widened to take this into account.

#### Summary points

The participation of local community members is a key element in HIV prevention worldwide

Despite the proliferation of community based approaches to HIV prevention, few studies have examined the role of social factors in a programme's success

In particular, little is known about why community participation affects sexual health

Community led peer education involves training local people to take control of HIV prevention efforts

This type of peer education in marginalised groups can create trusting and cooperative relationships in homogeneous local peer groups

The success of peer education also depends, however, on collaboration among diverse stakeholder groups at local, national, and international level

Among marginalised groups in poor countries, providing information about health risks changes the behaviour of, at most, one in four people—generally those who are more affluent and better educated.1 This is because health related behaviours (such …
Phylogenetic assessment of alignments reveals neglected tree signal in gaps
Authors: Christophe Dessimoz, Manuel Gil
Journal: Genome biology (2010)

Abstract Background The alignment of biological sequences is of chief importance to most evolutionary and comparative genomics studies, yet the two main approaches used to assess alignment accuracy have flaws: reference alignments are derived from the biased sample of proteins with known structure, and simulated data lack realism. Results Here, we introduce tree-based tests of alignment accuracy, which not only use large and representative samples of real biological data, but also enable the evaluation of the effect of gap placement on phylogenetic inference. We show that (i) the current belief that consistency-based alignments outperform scoring matrix-based alignments is misguided; (ii) gaps carry substantial phylogenetic signal, but are poorly exploited by most alignment and tree building programs; (iii) even so, excluding gaps and variable regions is detrimental; (iv) disagreement among alignment programs says little about the accuracy of resulting trees. Conclusions This study provides the broad community relying on sequence alignment with important practical recommendations, sets superior standards for assessing alignment accuracy, and paves the way for the development of phylogenetic inference methods of significantly higher resolution.
Autophagy in Cancer: Good, Bad, or Both?
Authors: Melanie M. Hippert, Patrick S. O'Toole, Andrew Thorburn
Journal: Cancer Research (2006)

Abstract Autophagy has been recognized as an important cellular process for at least 50 years; however, it is only with the recent identification of key regulators of autophagy (Atg genes) that we have begun a mechanistic exploration of its importance in cancer. Recent studies suggest that autophagy may be important in the regulation of cancer development and progression and in determining the response of tumor cells to anticancer therapy. However, the role of autophagy in these processes is complicated and may, depending on the circumstances, have diametrically opposite consequences for the tumor. In this article, we discuss recent discoveries regarding autophagy in cancer. (Cancer Res 2006; 66(19): 9349-51)
Abstract 1708: Induction of GDF15 by cisplatin triggers apoptotic cell death in ovarian cancer cells
Authors: Daisy I. Izaguirre, Zhifei Zu, Yvonne T. Tsang-Lee, Samuel Mok, Kwong-Kwok Wong
Journal: Cancer Research (2011)

Abstract Ovarian cancer is the fifth most common cause of death among women. The overall five year survival is 45.6% as a result of late diagnosis when treatment is mostly ineffective. Current treatment consists of complete resection followed by a combination of a taxane and a platinum -based chemotherapy regardless of the subtype. After standard treatment, 70% of patients will develop chemoresistance, creating a major challenge in the treatment of this type of cancer. Therefore, there is great interest in understanding the mechanisms by which tumors develop resistance. From the microarray data of a high grade serous ovarian cancer cell line (A2780) treated with varying concentrations of cisplatin and at varying time points, we identified four genes (CDKN1A, FDXR, TP53I3 and GDF15) which were significantly up-regulated by cisplatin in a time and dose dependent manner. The time and dose dependent upregulation of these genes were further validated by real-time RT-PCR and Western blot analysis in A2780 and two other ovarian cancer cell lines. We further tested whether GDF15 expression correlated with cisplatin response. RNA and protein from 6 different cell lines with different IC50 to cisplatin revealed a positive correlation between GDF15 induction and sensitivity to cisplatin. To further investigate the role GDF15 plays in the chemoresponse of ovarian cancer cell, we knocked down the expression of GDF15 by shRNA. Ovarian cancer cells with GDF15 knockdown showed a decrease in PARP cleavage, suggesting a pro-apoptotic role for GDF15. Thus, our results suggest that induction of GDF15 by cisplatin is one of the mechanisms that triggers apoptotic cell death in ovarian cancer cells. On the other hand, we were not able to detect an induction of GDF15 by cisplatin in a cisplatin resistant cell line A2780cp20. Thus, the lost of GDF15 induction could be one of the mechanisms of developing chemoresistance. Future studies to decipher the mechanism by which cisplatin induces GDF15 expression have the potential of identifying new targets that could circumvent chemoresistance to cisplatin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1708. doi:10.1158/1538-7445.AM2011-1708
Superior Vena Cava Syndrome Due to a Substernal Nontoxic Goiter
Authors: H VERLOOY, R MONTEYNE, J NOYEN, J COOLEN
Journal: Clinical Nuclear Medicine (1994)

Superior vena cava syndrome is a clinically well-recognized entity caused by malignant mediastinal neoplasms in 80% of Instances. A rare benign cause of the superior vena cava syndrome due to a retrosternal thyroid is presented. This case illustrates that it is the site of the mass and the completeness of obstruction, rather than the actual size of the mass, that determine the extent of collaterals that develop.
PREDICTORS ASSOCIATED WITH ACUTE STENT THROMBOSIS AFTER PRIMARY PCI: THE EUROMAX TRIAL
Authors: Peter Clemmensen, Arnoud van't Hof, Efthymios N. Deliargyris, Pierre Coste, Jurrien ten Berg, Claudio Cavallini, Martial Hamon, Dariusz Dudek, Uwe Zeymer, Xavier Tabone, Tim Clayton, Debra Bernstein, Jayne Prats
Journal: Journal of the American College of Cardiology (2014)
Alternaria spores at different heights from the ground
Authors: B. M. Bergamini, S. Grillenzoni, A. D. Andreoni, P. Natali, A. Ranzi, M. F. Bertolani
Journal: Allergy (2004)

Alternaria tenuis (Alt) is one of the main allergens in pediatric age. In temperate climates, airborne Alt spores are detectable from May to November with peaks in late summer and autumn. Sensitized children display symptoms even in the absence of airborne Alt spores. Alt spore concentration, as well as pollen, is usually detected by fixed devices located on the roof of a building at a height of 10-20 m. The aim of the current study is to find out whether ground-level (50 cm) Alt spore concentrations are different from those at roof-top level, even during low-concentration periods.Alt samples were taken simultaneously using a Hirst fixed volumetric collector (FVC) placed on a 15 m-high roof and by a portable volumetric collector (PVC). Firstly, the results of FVC and PVC, both placed on the roof-top, were compared to verify the correlation coefficient of the two samplers. Subsequently, the PVC was placed 50 cm above the ground in a courtyard (30 samplings) and in private green areas (50 samplings). The results were compared by statistical analysis (Student's t-test or K-S test).The values of the 20 samples taken jointly in summer time (FVC 195 +/- 134 spores/m(3); PVC = 134 +/- 131 spores/m(3)) showed a good correlation between the two samplers (r = 0.850; P < 0.01), with a correction factor equal to 1.177. 1. Thirty samples obtained in summer and winter when the PVC was positioned in an enclosed courtyard directly below the FVC showed no significant difference (PVC, 181 +/- 194 spores/m(3); FVC, 152 +/- 145 spores/m(3); P = 0.221). 2. Fifty samples taken by PVC placed in private green areas in a low-concentration period, showed significantly higher concentrations than by FVC: PVC, 531 +/- 925 spores/m(3); FVC, 25 +/- 51 spores/m(3) (K-S test: P < 0.0001). In particular, 33 samples taken in winter when Alt counts by FVC were <10 spores/m(3) still demonstrated highly significant differences: PVC, 398 +/- 961 spores/m(3); FVC, 2.0 +/- 2 spores/m(3) (K-S test: P < 0.0001).Our results lead to the conclusion that Alt spore concentration is significantly higher at ground level in the presence of vegetation, even when the spore concentration is very low (<10 spores/m(3)). These results further suggest that the individual's exposure to Alt, especially in the case of children, is underestimated by samples taken at roof-top level by FVC.
PLEKHM1 Regulates Salmonella-Containing Vacuole Biogenesis and Infection
Authors: David G. McEwan, Benjamin Richter, Beatrice Claudi, Christoph Wigge, Philipp Wild, Hesso Farhan, Kieran McGourty, Fraser P. Coxon, Mirita Franz-Wachtel, Bram Perdu, Masato Akutsu, Anja Habermann, Anja Kirchof, Miep H. Helfrich, Paul R. Odgren, Wim Van Hul, Achilleas S. Frangakis, Krishnaraj Rajalingam, Boris Macek, David W. Holden, Dirk Bumann, Ivan Dikic
Journal: Cell Host & Microbe (2014)
Photodynamic Therapy in Oncology: Mechanisms and Clinical Use
Authors: H. I. Pass
Journal: JNCI Journal of the National Cancer Institute (1993)

In photodynamic therapy (PDT), a sensitizer, light, and oxygen are used to cause photochemically induced cell death. The mechanism of cytotoxicity involves generation of singlet oxygen and other free radicals when the light-excited sensitizer loses or accepts an electron. Although selective retention of sensitizer by malignant tissue is seen in vivo, the mechanisms for this sensitizer targeting remain unclear. The first-generation sensitizers are porphyrin based and vary in lipophilicity and hydrophilicity. Targeting of the vasculature seems to be a prominent feature of the cytotoxic effect of these sensitizers in vivo, with resulting necrosis. Treatment depth varies with the wavelength of light that activates the sensitizer used, and the second-generation sensitizers are activated at longer wavelengths, allowing for a 30% increase in treatment depths. The selectivity of targeting can be increased when the sensitizer is delivered with the use of liposomes or monoclonal antibodies specific for tumor antigens. Studies have demonstrated direct effects of PDT on immune effector cells, specifically those with lineage from macrophages or other monocytes. Clinically, this therapy has been chiefly used for palliation of endobronchial and esophageal obstruction, as well as for treatment of bladder carcinomas, skin malignancies, and brain tumors. The future of PDT rests in defining its use either as an intraoperative adjuvant to marginal surgical procedures or as a primary treatment for superficial malignancies. Phase III trials in esophageal cancer and lung cancer are in progress and will help in evaluation of whether Photofrin II, the most widely used sensitizer, can be added to the oncologic armamentarium, pending approval from the U.S. Food and Drug Administration.