tbuckley/cabot-search huggingface dataset:
Implications for risk assessment of suggested nongenotoxic mechanisms of chemical carcinogenesis.
Authors: R L Melnick, M C Kohn, C J Portier
Journal: Environmental Health Perspectives (1996)

Nongenotoxic carcinogens are chemicals that induce neoplasia without it or its metabolites reacting directly with DNA. Chemicals classified as nongenotoxic carcinogens have been assumed to act as tumor promoters and exhibit threshold tumor dose-responses. This is in contrast to genotoxic carcinogens that are DNA reactive, act as tumor initiators, and are assumed to exhibit proportional responses at low doses. In this perspective, we examine the basic tenets and utility of this classification for evaluating human cancer risk. Two classes of so-called nongenotoxic chemical carcinogens selected for review include cytotoxic agents that induce regenerative hyperplasia (trihalomethanes and inducers of alpha 2-microglobulin nephropathy) and agents that act via receptor-mediated mechanisms (peroxisome proliferators and dioxin). Major conclusions of this review include: a) many chemicals considered to be nongenotoxic carcinogens actually possess certain genotoxic activities, and limiting evaluations of carcinogenicity to their nongenotoxic effects can be misleading; b) some nongenotoxic activities may cause oxidative DNA damage and thereby initiate carcinogenesis; c) although cell replication is involved in tumor development, cytotoxicity and mitogenesis do not reliably predict carcinogenesis; d) a threshold tumor response is not an inevitable result of a receptor-mediated mechanism. There are insufficient data on the chemicals reviewed here to justify treating their carcinogenic effects in animals as irrelevant for evaluating human risk. Research findings that characterize the multiple mechanisms of chemical carcinogenesis should be used quantitatively to clarify human dose-response relationships, leading to improved scientifically based public health decisions. Excessive reliance on oversimplified classification schemes that do not consider all potential contributing effects of a toxicant can obscure the actual causal relationships between exposure and cancer outcome.
Long-term hazards of neonatal blue-light phototherapy
Authors: J. Oláh, E. Tóth-Molnár, L. Kemény, Z. Csoma
Journal: British Journal of Dermatology (2013)

Blue-light phototherapy has been an essential therapeutic tool in the management of neonatal jaundice for decades. Rarely, it is accompanied by acute dermatological and systemic side-effects, but fortunately these are reversible and can be adequately and promptly treated in routine neonatal practice. In contrast, much less is known about the potential long-term side-effects of neonatal blue-light phototherapy (NBLP). Many of the data that are currently available on how NBLP influences melanocytic naevus (MN) development are controversial. The results of recent well-designed epidemiological surveys suggest that NBLP could well be a risk factor for MN formation, and highlight the need for additional in vivo and in vitro studies. NBLP is at present the mainstay of treatment for neonatal jaundice, but in the future greater consideration should be given to its long-term side-effects when phototherapy is indicated. It is relevant to emphasize the importance of appropriately restricted and adequate clinical guidelines, and strict monitoring of the management of hyperbilirubinaemia, in order to avoid the unnecessary overtreatment of newborn infants.
Care in Chaos
Authors: J. Leff
Journal: BMJ (1996)

Roger Hadley, Roger Clough Cassell, £15.99, pp 226 ISBN 0 304 33525 8

The 1990 NHS and Community Health Act was a watershed for all of us working in healthcare. The act established the internal market, the central tenet of which is that health is a commodity that can be bought and sold and hence needs to be measured quantitatively. This is a testable proposition, but the reform was not introduced in an experimental vein. It was imposed without consultation with the NHS workforce, in the belief that it would work. In this respect it can be seen as an example of what Popper termed “utopian engineering.”

Six years after the act, is …
“Boiler Crud” in Urinary Pipes
Authors: John Eager Howard
Journal: New England Journal of Medicine (1972)

The mechanisms whereby concretions form and grow in the urinary tract are still unknown; direct therapeutic approach to their prevention is therefore impossible. Over the years many theories have been proposed pertaining to the etiology of calcific kidney stones, but none as yet have stood the test of experimental investigation. Reasons for this continuing state of ignorance can be readily suggested: perhaps the two most obvious are absence of an experimental model that exactly mimics the circumstances under which stones are initiated and grow in the urinary tracts, and lack of basic knowledge concerning the laws of formation and resorption . . .
New NHS board should leave job of commissioning to clinical groups
Authors: H. Mooney
Journal: BMJ (2011)

The role of England’s new NHS Commissioning Board should be strictly defined so that it will have only certain agreed tasks, such as setting new terms and conditions or bringing in new primary care providers into local areas if current provision or choice is insufficient, a Department of Health official has admitted.

Ben Dyson, director of policy, commissioning, and primary care at the department, told NHS managers at the NHS Confederation’s annual conference this week that there was “tension” in the fact that the NHS Commissioning Board would have responsibility for commissioning when the “real job of commissioning” needed …
Thrombin Activity and Early Outcome in Unstable Angina Pectoris
Authors: Diego Ardissino, Piera Angelica Merlini, Gabriella Gamba, Paolo Barberis, Gloria Demicheli, Sophie Testa, Elisabetta Colombi, Arnaldo Poli, Raffaela Fetiveau, Carlo Montemartini
Journal: Circulation (1996)

Background The blood coagulation system is frequently activated in the acute phase of unstable angina, but it is unknown whether the augmented function of the hemostatic mechanism may serve as a marker of increased risk for an early unfavorable outcome. Methods and Results Plasma concentrations and 24-hour urinary excretion of fibrinopeptide A were prospectively determined in 150 patients with unstable angina. All patients underwent 24-hour Holter monitoring, during which time urine was collected; at the end of this period, a blood sample was taken and coronary arteriography was performed. The patients were followed up for the occurrence of cardiac events (death and myocardial infarction) until they underwent coronary revascularization or until they were discharged from the hospital. Fibrinopeptide A plasma levels and 24-hour urinary excretion were found to be abnormally elevated in 50% and 45% of the study population, respectively. During hospitalization, 11 patients developed myocardial infarction and 2 patients died. Kaplan-Meier analysis demonstrated a significantly higher probability of developing cardiac events in patients with abnormal rather than normal plasma levels of fibrinopeptide A ( P &lt;.01), whereas no difference in outcome was observed between patients with normal and those with abnormal 24-hour urinary excretion. Cox regression analysis showed that the only variables independently related to an early unfavorable outcome were the presence of persistent ischemia during 24-hour Holter monitoring ( P &lt;.0001), the presence of intracoronary thrombosis at angiography ( P =.016), and abnormal fibrinopeptide A plasma levels ( P =.038). Conclusions Patients with unstable angina pectoris and abnormal fibrinopeptide A plasma levels are at increased risk for an early unfavorable outcome.
Measurement of tracheobronchial clearance after sauna in subjects with chronic bronchitis.
Authors: M van Hengstum, J Festen, F Corstens
Journal: Thorax (1991)

The effect of sauna on tracheobronchial clearance was studied in five male patients with chronic bronchitis by a radioaerosol technique. No enhancement of tracheobronchial clearance could be detected.
Monosomal karyotype in MDS: explaining the poor prognosis?
Authors: J Schanz, H Tüchler, F Solé, M Mallo, E Luño, J Cervera, J Grau, B Hildebrandt, M L Slovak, K Ohyashiki, C Steidl, C Fonatsch, M Pfeilstöcker, T Nösslinger, P Valent, A Giagounidis, C Aul, M Lübbert, R Stauder, O Krieger, M M Le Beau, J M Bennett, P Greenberg, U Germing, D Haase
Journal: Leukemia (2013)
Environmental Influence on Implantable Cardiac Pacemakers
Authors: Richard A. Carleton, Robert W. Sessions, John S. Graettinger
Journal: JAMA (1964)

IMPLANTABLE CARDIAC PACEMAKERS are being used with increasing frequency in the management of patients with symptoms of a complete heart block. Although electromechanical control of heart rate would seem to demand a high level of both knowledge and professional concern regarding interactions between pacemakers and the environment, little information is available in scientific journals. We are, therefore, reporting preliminary observations of the behavior of two brands of pacemakers in several environments which may be encountered by patients.  Material and Methods  Three pacemakers have been used. Two were designed and made by one of us (R. W. S.) and are of the type used in 26 patients treated in this institution.1,2One of these had the long lead wires intact, the other had them removed to ensure that any induction currents or alterations of function which were detected had originated within the pacemaker unit itself. The third pacemaker, a popular,
Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA): development and validation of a tool for assessment of nail psoriasis outcomes
Authors: M. Augustin, C. Blome, A. Costanzo, E. Dauden, C. Ferrandiz, G. Girolomoni, R. Gniadecki, L. Iversen, A. Menter, K. Michaelis-Wittern, A. Morita, H. Nakagawa, K. Reich
Journal: British Journal of Dermatology (2013)

Existing tools for nail psoriasis are complex and may not adequately measure outcomes that are important to patients.We have developed and validated a new tool, the Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA), with three components: a questionnaire assessing quality of life (NAPPA-QoL), a two-part questionnaire assessing patient-relevant treatment benefits (the Patient Benefit Index, NAPPA-PBI) and a psoriasis Clinical Assessment of Severity (NAPPA-CLIN).Development of the questionnaires involved multiple steps: (i) collection of items about nail psoriasis-related impairments and treatment goals; (ii) selection of 48 items by an expert panel, including patients; (iii) translation into eight languages; (iv) feasibility testing and (v) longitudinal validation in six countries.Patients found the questionnaires clear (84%) and comprehensible (95%). NAPPA-QoL and NAPPA-PBI scores correlated moderately with clinical outcomes [e.g. Nail Psoriasis Severity Index (NAPSI)] and markedly with other quality-of-life questionnaires (e.g. EQ-5D™). Both questionnaires were sensitive to change. Internal consistency was good (Cronbach α ≥ 0.88 for all scales). The NAPPA-CLIN, a brief version of NAPSI that involves assessment of only four digits rather than all 20, was found to correlate highly with total NAPSI score (r = 0.97, P < 0.001).Overall, the three-component NAPPA tool is a valid, reliable and practical instrument to assess patient-relevant nail psoriasis outcomes.
Thyroiditis and Thyroid Function: Clinical, Morphological, and Physiopathological Studies
Authors: Samuel Refetoff
Journal: JAMA (1972)

The authors have done an admirable job in coherently presenting the multiple facets of thyroiditis and thyroid diseases. The biochemical, functional, pathological, clinical, hereditary, and autoimmune aspects of thryoiditis are expounded in 15 carefully planned and well-organized chapters. The first two chapters are introductory, dealing with the normal structure and function of the thyroid gland and the general principles and theories of autoimmunity. The bulk of the book is devoted to discussions of each variant of thyroiditis. Carefully structured, the presentations include the clinical features, pathological and laboratory findings, iodide and hormone metabolism, etiology, diagnosis, and therapy. Illustrative case histories for each disease entity are concise and very instructive. The concluding chapters deal with chromosomal abnormalities, heredity, and diseases associated with thyroiditis, which strengthen the main object of the book, namely the understanding of the mechanisms responsible for this intriguing disease entity. The number of references quoted at the end
Christmas firework "sweets" kill hundreds of children
Authors: C. Wallerstein
Journal: BMJ (1999)

Health experts in the Philippines are pleading for a ban on “watusi,” a popular Christmas firework, which has caused the deaths of hundreds of children through phosphorus poisoning.

Each year dozens of young children are killed or disabled after eating the brightly coloured traditional fireworks, mistaking them for sweets.

Watusi is sold in corner shops or by street vendors for less than one peso (1.5 p; …
Retrospective Address of the Third Anniversary of the Reading Pathological Society
Authors: I. Harrinson
Journal: BMJ (1844)

The stomach of a man supposed to have died from thie effects of oxalic acid.It contained 1r ounces of dark bloody fluid; the esopbagus was inflamed.He promaised a paper on the subject.11.Mr. May.A portion of intestine taken from a man, aged 77, who died from strangulated hlernia on the fiftlh day.He was found in a state of collapse, and no operation was justifiable.On inspection one half of the cylinder of the ileum was strangulated, sphacelated, but without inflammation.He had had no pain except a little at the umbilicus the first day.Mr. May then said that pain was not a symptom to be relied on in hernia, though generally coonsidered diag- nostic.Two cases had occurred to him where the hernia became strangulated and death followed, without the patients having had any pain in the tumour.He tbought the true surgical rule was, where there was tumour at some of the ordinary places of rupture, with symptoms of incarceration, to cut down on the tumour and ascertain its true nature.The length of time which occurred between strangulation and death was another circumstance worthy of attention, and he instanced the case of an old lady who was well at night;
Factor VIII, D-Dimer, and Thromboembolism in Children
Authors: Ulrike Nowak-Göttl, Andrea Kosch
Journal: New England Journal of Medicine (2004)

Symptomatic venous and arterial thromboses are being diagnosed with increasing frequency in neonates, infants, and children. Because of the special properties of the hemostatic system in children, thrombotic manifestations are not rare in the pediatric population: they occur in 0.07 of every 10,000 children and account for 5.3 of every 10,000 pediatric hospital admissions and 2.4 of every 1000 admissions of newborns to intensive care units. Perhaps the lower concentrations of physiological inhibitors of the coagulation system, along with more limited fibrinolytic capacity, account for the greater risk of thromboembolic complications among neonates than among older children. The incidence of . . .
Israeli infertility experts investigated for "selling" ova
Authors: J. Siegel-Itzkovich
Journal: BMJ (2000)

Two of Israel's most senior infertility specialists have been put under police investigation for allegedly overstimulating the ovaries of patients in order to produce large numbers of ova, which they then “sold” for treating infertile women in Israel and abroad.

The investigation, which began several months ago, has sent shock waves through the obstetrics specialty and has led to the formation of a health ministry committee of experts to recommend ways to alleviate the shortage of donated ova.

According to Israeli law, no woman may donate spare ova unless she herself is receiving infertility treatment. Aimed at “preventing” sales …
Abstract 318: Specific role of Mieap α in Mieap-induced vacuole generation through an interaction with UVRAG
Authors: Yasuyuki Nakamura, Hiroki Kamino, Yuri Saito, Noriaki Kitamura, Hitoya Sano, Hirofumi Arakawa
Journal: Cancer Research (2014)

Abstract Mieap, a p53-inducible protein, controls mitochondrial quality by repairing or eliminating unhealthy mitochondria via Mieap-induced accumulation of lysosome-like organelles within mitochondria (MALM) or Mieap-induced vacuole (MIV), respectively (1-4). BNIP3 and NIX are essential mediators of MALM. MIV generation is closely related to the endocytic pathway. However, the mechanism of MALM and MIV function and of their selection and regulation remains unclear. UVRAG was identified as a Mieap-interacting protein. UVRAG plays a role in canonical autophagy through the endocytic pathway. Interestingly, Mieap α, but not Mieap β, specifically interacts with UVRAG. Knockdown of UVRAG severely inhibited MIV generation induced by Mieap α. On the other hand, endogenous Mieap β, but not Mieap α, accumulated at and within mitochondria during the MALM process. These results, taken together, suggest that Mieap α has a specific role in MIV generation through an interaction with UVRAG by regulating the endocytic pathway. In addition, UVRAG and Mieap are inactivated in human cancers including colorectal cancer patients, suggesting that the MIV regulated by the interaction of Mieap and UVRAG may play a role in tumor suppression. In this paper, we discuss several possible mechanisms for the selection of MALM or MIV and the role of Mieap/UVRAG in tumorigenesis on the basis of our recent data. 1. Miyamoto Y et al. PLoS ONE 6: e16054, 2011 2. Kitamura N et al. PLoS ONE 6: e16060, 2011 3. Nakamura Y et al. PLoS ONE 7: e30767, 2012 4. Miyamoto T et al. Sci Rep 2: 379, 2012 Citation Format: Yasuyuki Nakamura, Hiroki Kamino, Yuri Saito, Noriaki Kitamura, Hitoya Sano, Hirofumi Arakawa. Specific role of Mieap α in Mieap-induced vacuole generation through an interaction with UVRAG. [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 318. doi:10.1158/1538-7445.AM2014-318
Points: Recognising placental steroid sulphatase deficiency
Authors: R A Harkness
Journal: BMJ (1983)

write: Dr Lightman (6 August, p 422) has missed the point.We were not reviewing the variety of lesions that might provoke hot flushes.The object of our case presentation (23 July, p 262) was the objective demonstration that climacteric flushing in a man was associated with circulatory responses virtually identical to those we had shown during the meno- pausal hot flush.'Every blush is not a flush, however, and until the phenomena reported in different circumstances in either sex are recorded by tech- niques capable of following the rapid circulatory changes that occur during the hot flush our under- standing of the mechanisms responsible for the menopausal hot flush will remain obscure.
Abstract LB-80: Role of ER calcium in Bcl-2 resistance to dosage and duration-related cytotoxic efficacy of Taxol
Authors: Zhi Pan, Lauren Gollahon
Journal: Cancer Research (2012)

Abstract Background and Objectives: Calcium is one of the key regulators in apoptosis. Among various calcium sources, our previous study shows that the endoplasmic reticulum (ER), the main intracellular calcium storage site, provides a specific target for the chemotherapy agent Taxol and thus contributes to apoptosis. Although the expression of the anti-apoptotic protein Bcl-2 has been shown to confer resistance to Taxol, the exact mechanism of how it inhibits apoptosis and the role of ER calcium in this process remains unclear. This study investigated whether ER-associated calcium changes were generated and related to resistance by Bcl-2 to Taxol-induced apoptosis. Materials and methods: Fluo4-AM and Cameleon D1ER was used to monitor cytosolic and ER calcium dynamics by advanced time-lapsed imaging. Annexin V-FITC and propidium iodide were used to detect various phases of apoptosis induced by Taxol at different dosages from 10−12 to 10−5 M and at different durations from 5 min to 12 hours. Breast cancer cell lines MDA-MB-M468 and MDA-MB-231 were used and Bcl-2 transfectant cell lines were constructed by stable transfection. Results and Significance: Our previous data shows that Taxol (above 10−6 M) induces a rapid ER calcium release (peaking at 5 minutes) that promotes apoptosis. In this study, upon the expression of Bcl-2, basal ER calcium levels are decreased and Taxol-induced ER calcium release is inhibited, playing a major role in Bcl-2 resistance to Taxol. Depending upon dose and exposure time, long-term (hours) Taxol treatment partially overcame the Bcl-2 inhibition of ER calcium release by continually stimulating the ER calcium release, ultimately inducing significant, although smaller apoptosis in the presence of Bcl-2 expression. In addition to the effect on ER calcium, our data shows that the extracellular calcium pool is involved in Bcl-2 resistance through increased capacitative calcium entry to refill the ER calcium store, preventing ER calcium depletion. Taxol does not have a significant effect on the enhanced calcium influx from the extracellular medium. Taken together, out results indicate that the ER calcium store is the focus of the Taxol attack and plays a key role in Bcl-2 resistance to cytotoxic efficacy of Taxol in breast cancer cells. This finding provides insight to better understand the complex relationship between Bcl-2, calcium and Taxol towards improving breast cancer chemotherapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-80. doi:1538-7445.AM2012-LB-80
5-YEARS CLINICAL OUTCOMES OF KNOWN DIABETES MELLITUS AND NEWLY DIAGNOSED DIABETES AND PREDIABETES AMONG PATIENTS WITH ACUTE MYOCARDIAL INFARCTION UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION
Authors: Donggyu Moon, Jae Gyung Kim, Jin Jin Kim, Sungmin Lim, Ik Jun Choi, Eun Ho Choo, Pum Joon Kim, Kiyuk Chang, Wook Sung Chung, Ki-Bae Seung, Chul Soo Park, Tae-Hoon Kim, Yoon Seok Koh, Jong Min Lee, Suk Min Seo, Dong Il Shin, Sang-Hyun Ihm
Journal: Journal of the American College of Cardiology (2014)