tbuckley/cabot-search huggingface dataset:
Acute myeloid leukemia: 2012 update on diagnosis, risk stratification, and management
Authors: Elihu H. Estey
Journal: American Journal of Hematology (2011)

Acute myeloid leukemia (AML) results from accumulation of abnormal immature cells in the marrow. These cells interfere with normal hematopoiesis can escape into the blood and infiltrate lung and CNS. The most common cause of death is bone marrow failure. It is likely that many different mutations and/or epigenetic aberrations can produce the same disease, with these differences responsible for the very variable response to therapy, which is AML's principal clinical feature.This rests on demonstration that the marrow or blood has >20% blasts of myeloid lineage. Blast lineage is assessed by multiparameter flow cytometry with CD33 and CD13 being surface markers typically expressed by myeloid blasts. It should be realized that clinical/prognostic considerations, not the blast % per se, should be the main factor determining how a patient is treated.Two features determine risk: the probability of treatment-related mortality (TRM) and, more important, even in patients aged >75 with Zubrod performance status 1, the probability of resistance to standard therapy despite not incurring TRM. The chief predictor of resistance is cytogenetics with a monosomal karyotype (MK) denoting the disease is essentially incurable with standard therapy even if followed by a standard allogeneic transplant (HCT). The most common cytogenetic finding is a normal karyotype (NK) and those of such patients with an NPM1 mutation but no FLT3 internal tandem duplication (ITD), or with a CEBPA mutation, have a prognosis similar to that of patients with the most favorable cytogenetics [inv(16) or t(8;21)] (60-70% cure rate). In contrast, NK patients with a FLT3 ITD have only a 30-40% chance of cure even after HCT. Accordingly analyses of NPM1, FLT3, and CEBPA should be part of routine evaluation, much as is cytogenetics. Risk is best assessed considering several variables simultaneously rather than, for example, only age.Patients with inv(16) or t(8;21) or who are NPM1+/FLT3ITD- can receive standard therapy (daunorubicin + cytarabine) and should not receive HCT in first CR. It seems likely that use of a daily daunorubicin dose of 90 mg/m(2) will further improve outcome in these patients. There appears no reason to use doses of cytarabine > 1 g/m(2) (for example, bid × 6 days), as opposed to the more commonly used 3 g/m(2) . Patients with an unfavorable karyotype (particularly MK) are unlikely to benefit from standard therapy (even with dose escalation) and are thus prime candidates for clinical trials of new drugs or new approaches to HCT; the latter should be done in first CR. Patients with intermediate prognoses (for example, NK and NPM and FLT3ITD negative) should also receive HCT in first CR and can plausibly receive either investigational or standard induction therapy, with the same prognostic information about standard therapy leading one patient to choose the standard and another an investigational option.
Transcatheter treatment of atrial septal aneurysm associated with patent foramen ovale for prevention of recurrent paradoxical embolism in high-risk patients
Authors: Andreas Wahl, Bernhard Meier, Markus Schwerzmann, Ulf Becker, Christian Seiler, Marcel Arnold, Heinrich P. Mattle, Ulrike Krumsdorf, Horst Sievert, Stephan Ostermayer, Kai Billinger, Stephan Windecker, Stephan Ostermayer
Journal: Journal of the American College of Cardiology (2005)
Arrhythmias during Intracardiac Catheterization
Authors: J. MICHEL, A. D. JOHNSON, W. C. BRIDGES, J. H. LEHMANN, F. GRAY, L. FIELD, D. M. GREEN
Journal: Circulation (1950)

This paper summarizes the incidence of various arrhythmias in an unselected series of cardiac catheterizations and presents evidence for their reflex origin in some instances. The hazards are discussed and comments made about prophylaxis and treatment.
Physical dependence on zopiclone
Authors: S. Sikdar, O. Ayonrinde, E. Sampson
Journal: BMJ (1998)

Editor—I was interested to read Jones and Sullivan’s report on dependence on zopiclone1 because Ruben and I had earlier reported six cases of misuse of zopiclone among polydrug users in Liverpool.2 The average daily dose of zopiclone was 105 mg (range 90-380 mg) and the average duration of use 10 months (6-24 months). All the patients initially used the drug for sleeping but later developed tolerance to its sedative property. Common daytime side effects reported were drowsiness, dry mouth, nausea, ataxia, and psychomotor slowing. The main withdrawal symptoms reported were rebound insomnia, a feeling of being edgy, and a strong craving 6-8 hours after the last dose. This led to self treatment to obtain relief from the withdrawal symptoms. None of the patients injected the drug, primarily because they did not know that it could be injected. All the patients were previous misusers of temazepam and preferred zopiclone because it did not cause amnesia as temazepam did. Two patients even forged prescriptions to obtain the drug. 

Worryingly, all the patients admitted to knowing many other addicts who were misusing zopiclone and said that it was growing in popularity among addicts as a safe and strong sedative. The misuse of zopiclone is yet another example of iatrogenic misuse of a drug marketed enthusiastically by its manufacturers as a non-addictive substitute, as has been reported for carisoprodol3 and buprenorphine.4 Zopiclone is being prescribed as a sedative freely by both general practitioners and psychiatrists. Awareness of its potential for misuse needs to spread, and caution needs to be exercised in its prescription.
Predictive factors for ischemic target vessel revascularization in the Prevention of Restenosis with Tranilast and its Outcomes (PRESTO) trial
Authors: Mandeep Singh, Bernard J. Gersh, Robyn L. McClelland, Kalon K.L. Ho, James T. Willerson, William F. Penny, David R. Holmes
Journal: Journal of the American College of Cardiology (2005)
Prognostic Significance of Co-expression of RON and MET Receptors in Node-Negative Breast Cancer Patients
Authors: Wen-Ying Lee, Helen H.W. Chen, Nan-Haw Chow, Wu-Chou Su, Pin-Wen Lin, How-Ran Guo
Journal: Clinical Cancer Research (2005)

RON and MET belong to a subfamily of tyrosine kinase receptors. They both can induce invasive growth, including migration, cell dissociation, and matrix invasion. Cross-linking experiments show that RON and MET form a noncovalent complex on the cell surface and cooperate in intracellular signaling. We wanted to examine the clinical significance of RON and MET expression patterns in node-negative breast cancer.We studied the protein expressions of RON and MET in five breast cancer cell lines and a homogeneous cohort of 103 T(1-2)N(0)M(0) breast carcinoma patients, including 52 patients with distant metastases and 51 patients with no evidence of disease after at least a 10-year follow-up.Both HCC1937 and MDA-MB-231 cancer cell lines co-overexpressed RON and MET. The MCF-7 cell line did not express RON or MET. In multiple logistic regression analysis, RON expression (odds ratio, 2.6; P = 0.05) and MET expression (odds ratio, 4.7; P = 0.009) were independent predictors of distant relapse. RON+/MET+ and RON-/MET+ tumors resulted in a large risk increase for 10-year disease-free survival after adjusting for tumor size, histologic grade, estrogen receptor, bcl-2, HER-2/neu, and p53 status by multivariate Cox analysis (risk ratio, 5.3; P = 0.001 and risk ratio, 3.76; P = 0.005). The 10-year disease-free survival was 79.3% in patients with RON-/MET- tumors, was only 11.8% in patients with RON+/MET+ tumors, and was 43.9% and 55.6% in patients with RON-/MET+ and RON+/MET- tumors.Co-expression of RON and MET seems to signify an aggressive phenotype in node-negative breast cancer patients.
Retroperitoneal fibrosis associated with atenolol.
Authors: D W Bullimore
Journal: BMJ (1980)

non-crying babies.Hutt7 describes parallels.High pulse rates have been found in withdrawn psychotic patients.8While preparing a paper on adolescent suicide attempts in this health district over 12 months I noted that, with a few exceptions, both the mothers' memory and medical records indicated that the 40 teenagers were non-crying babies.I had hoped to entitle the presentation "The unheard cry growing up."Although, as Dunn surmises,2 parents and babies are allowed time to adjust and early reactions are certainly not exclusively all- important for future emotional development, awareness of "silent" infant protest is im- portant.We can then deal with causative factors and learn to contain also the anxiety or aggression arising therefrom.
Inhibition of Glycogen Synthase Kinase 3β During Heart Failure Is Protective
Authors: Shinichi Hirotani, Peiyong Zhai, Hideharu Tomita, Jonathan Galeotti, Juan Pablo Marquez, Shumin Gao, Chull Hong, Atsuko Yatani, Jesús Avila, Junichi Sadoshima
Journal: Circulation Research (2007)

Glycogen synthase kinase (GSK)-3, a negative regulator of cardiac hypertrophy, is inactivated in failing hearts. To examine the histopathological and functional consequence of the persistent inhibition of GSK-3beta in the heart in vivo, we generated transgenic mice with cardiac-specific overexpression of dominant negative GSK-3beta (Tg-GSK-3beta-DN) and tetracycline-regulatable wild-type GSK-3beta. GSK-3beta-DN significantly reduced the kinase activity of endogenous GSK-3beta, inhibited phosphorylation of eukaryotic translation initiation factor 2B epsilon, and induced accumulation of beta-catenin and myeloid cell leukemia-1, confirming that GSK-3beta-DN acts as a dominant negative in vivo. Tg-GSK-3beta-DN exhibited concentric hypertrophy at baseline, accompanied by upregulation of the alpha-myosin heavy chain gene and increases in cardiac function, as evidenced by a significantly greater Emax after dobutamine infusion and percentage of contraction in isolated cardiac myocytes, indicating that inhibition of GSK-3beta induces well-compensated hypertrophy. Although transverse aortic constriction induced a similar increase in hypertrophy in both Tg-GSK-3beta-DN and nontransgenic mice, Tg-GSK-3beta-DN exhibited better left ventricular function and less fibrosis and apoptosis than nontransgenic mice. Induction of the GSK-3beta transgene in tetracycline-regulatable wild-type GSK-3beta mice induced left ventricular dysfunction and premature death, accompanied by increases in apoptosis and fibrosis. Overexpression of GSK-3beta-DN in cardiac myocytes inhibited tumor necrosis factor-alpha-induced apoptosis, and the antiapoptotic effect of GSK-3beta-DN was abrogated in the absence of myeloid cell leukemia-1. These results suggest that persistent inhibition of GSK-3beta induces compensatory hypertrophy, inhibits apoptosis and fibrosis, and increases cardiac contractility and that the antiapoptotic effect of GSK-3beta inhibition is mediated by myeloid cell leukemia-1. Thus, downregulation of GSK-3beta during heart failure could be compensatory.
PHYSIOTHERAPY FIRST: NATURE'S MEDICAMENTS BEFORE DRUG REMEDIES; PARTICULARLY RELATING TO HYDROTHERAPY.Read at the last Semi-annual Meeting, in Ottawa, of the Rideau and Bathurst Medical Association.
Authors: EDWARD PLAYTER
Journal: JAMA (1894)

All through the records of the history of medicine—in the early Assyrian and Egyptian period, five or six thousand years ago, in the time of Æsculapius and of Hippocrates and down, as we find in modern uncivilized tribes, we have clear evidence that in the first or early steps in the science of medicine the practice of the art consisted for the most part in the employment of magical incantations, the laying on of hands, etc., and was apparently somewhat of the nature of modern hypnotism, acting through the mind, as if the chief reliance in the healing of disease was upon the natural living forces within the body. We are here reminded of the old saying that "God made man upright, but he hath sought out many inventions." Although Æsculapius in his practice, we are told, enjoined first of all a hygienic regimen, attention to the diet, strict temperance
Osteoblastic Lesions of Unusual Nature
Authors: Robert W. Courey
Journal: JAMA (1972)

Dr. David J. Rushforth: This 55-year-old woman was admitted for evaluation of osteoblastic lesions, which had been noted incidentally during an examination of the colon by barium enema. She had been well until one month previously when she consulted her physician because of watery, painless diarrhea of several weeks' duration. No blood had been noticed in the stool. Other symptoms included mild low-back pain and muscular stiffness, a numb feeling in her feet, and a one-year history of pruritus. Physical examination disclosed a single, small, fixed supraclavicular lymph node in an obese woman. Results of the remainder of the examination were noncontributory. Findings from neurological examination were described as "physiological." Two examiners thought that the right lobe of the thyroid was slightly enlarged, but not nodular. Her breasts were normal to palpation. The patient was readmitted three months later for increasing numbness and weakness. On physical examination a neurological deficit
Clinical and Genetic Heterogeneity of Right Bundle Branch Block and ST-Segment Elevation Syndrome
Authors: Silvia G. Priori, Carlo Napolitano, Maurizio Gasparini, Carlo Pappone, Paolo Della Bella, Michele Brignole, Umberto Giordano, Tiziana Giovannini, Carlo Menozzi, Raffaella Bloise, Lia Crotti, Liana Terreni, Peter J. Schwartz
Journal: Circulation (2000)

Background —The ECG pattern of right bundle branch block and ST-segment elevation in leads V 1 to V 3 (Brugada syndrome) is associated with high risk of sudden death in patients with a normal heart. Current management and prognosis are based on a single study suggesting a high mortality risk within 3 years for symptomatic and asymptomatic patients alike. As a consequence, aggressive management (implantable cardioverter defibrillator) is recommended for both groups. Methods and Results —Sixty patients (45 males aged 40±15 years) with the typical ECG pattern were clinically evaluated. Events at follow-up were analyzed for patients with at least one episode of aborted sudden death or syncope of unknown origin before recognition of the syndrome (30 symptomatic patients) and for patients without previous history of events (30 asymptomatic patients). Prevalence of mutations of the cardiac sodium channel was 15%, demonstrating genetic heterogeneity. During a mean follow-up of 33±38 months, ventricular fibrillation occurred in 5 (16%) of 30 symptomatic patients and in none of the 30 asymptomatic patients. Programmed electrical stimulation was of limited value in identifying patients at risk (positive predictive value 50%, negative predictive value 46%). Pharmacological challenge with sodium channel blockers was unable to unmask most silent gene carriers (positive predictive value 35%). Conclusions —At variance with current views, asymptomatic patients are at lower risk for sudden death. Programmed electrical stimulation identifies only a fraction of individuals at risk, and sodium channel blockade fails to unmask most silent gene carriers. This novel evidence mandates a reappraisal of therapeutic management.
Impact of effects of acid precipitation on toxicity of metals.
Authors: G F Nordberg, R A Goyer, T W Clarkson
Journal: Environmental Health Perspectives (1985)

Acid precipitation may increase human exposure to several potentially toxic metals by increasing metal concentrations in major pathways to man, particularly food and water, and in some instances by enhancing the conversion of metal species to more toxic forms. Human exposures to methylmercury are almost entirely by way of consumption of fish and seafood. In some countries, intakes by this route may approach the levels that can give rise to adverse health effects for population groups with a high consumption of these food items. A possible increase in methylmercury concentrations in fish from lakes affected by acid precipitation may thus be of concern to selected population groups. Human exposures to lead reach levels that are near those associated with adverse health effects in certain sensitive segments of the general population in several countries. The possibility exists that increased exposures to lead may be caused by acid precipitation through a mobilization of lead from soils into crops. A route of exposure to lead that may possibly be influenced by acid precipitation is an increased deterioration of surface materials containing lead and a subsequent ingestion by small children. A similar situation with regard to uptake from food exists for cadmium (at least in some countries). Human metal exposures via drinking water may be increased by acid precipitation. Decreasing pH increases corrosiveness of water enhancing the mobilization of metal salts from soil; metallic compounds may be mobilized from minerals, which may eventually reach drinking water. Also, the dissolution of metals (Pb, Cd, Cu) from piping systems for drinking water by soft acidic waters of high corrosivity may increase metal concentrations in drinking water. Exposures have occasionally reached concentrations which are in the range where adverse health effects may be expected in otherwise healthy persons. Dissolution from piping systems can be prevented by neutralizing the water before distribution. Increased aluminum concentrations in water is a result mainly of the occurrence of Al in acidified natural waters and the use of Al chemicals in drinking water purification. If such water is used for dialysis in patients with chronic renal failure, it may give rise to cases of dialysis dementia and other disorders. A possible influence on health of persons with normal renal function (e.g., causing Alzheimer's disease) is uncertain and requires further investigation.(ABSTRACT TRUNCATED AT 400 WORDS)
Irreversible binding of conjugated bilirubin to albumin in cholestatic rats.
Authors: A Gautam, H Seligson, E R Gordon, D Seligson, J L Boyer
Journal: Journal of Clinical Investigation (1984)

A diazo-positive fraction of serum bilirubin that is irreversibly bound to albumin has been shown to accumulate in serum of patients with cholestasis. In the present study, a cholestatic animal model was used to determine the chemical nature of the bilirubin species involved in its formation. The data indicate that conjugated bilirubin is the precursor of "albumin-bound bilirubin" and that the presence or absence of light does not affect its formation. An albumin-bound bilirubin-complex indistinguishable from the complex detected in cholestatic sera from patients or in bile duct-ligated Sprague-Dawley rats can be formed in vitro in sera enriched in conjugated bilirubin at 37 degrees C, pH 7.4.
Asbestos and cancer: An overview of current trends in Europe.
Authors: M Albin, C Magnani, S Krstev, E Rapiti, I Shefer
Journal: Environmental Health Perspectives (1999)

This review assesses the contribution of occupational asbestos exposure to the occurrence of mesothelioma and lung cancer in Europe. Available information on national asbestos consumption, proportions of the population exposed, and exposure levels is summarized. Population-based studies from various European regions on occupational asbestos exposure, mesothelioma, and lung cancer are reviewed. Asbestos consumption in 1994 ranged, per capita, between 0. 004 kg in northern Europe and 2.4 kg in the former Soviet Union. Population surveys from northern Europe indicate that 15 to 30% of the male (and a few percent of the female) population has ever had occupational exposure to asbestos, mainly in construction (75% in Finland) or in shipyards. Studies on mesothelioma combining occupational history with biologic exposure indices indicate occupational asbestos exposure in 62 to 85% of the cases. Population attributable risks for lung cancer among males range between 2 and 50% for definite asbestos exposure. After exclusion of the most extreme values because of methodologic aspects, most of the remaining estimates are within the range of 10 to 20%. Estimates of women are lower. Extrapolation of the results to national figures would decrease the estimates. Norwegian estimates indicate that one-third of expected asbestos-related lung cancers might be avoided if former asbestos workers quit smoking. The combination of a current high asbestos consumption per capita, high exposure levels, and high underlying lung cancer rates in Central Europe and the former Soviet Union suggests that the lung cancers will arise from the smoking-asbestos interaction should be a major concern.
Dipping into the Queen's Speech
Authors: W. Russell
Journal: BMJ (1980)

One thing Mr Norman St John-Stevas, leader of the House of Commons, promised earlier this year was that the 1980-1 parliamentary timetable was not going to be overloaded with legislation. A quiet life for a change, it seemed, awaited MPs. Alas, this is now said to be unlikely. The new session, which opens on Thursday 20 November, is starting late. So the Government is going to be pushed for time to complete its programme within the parliamentary year, which will last until about the end of October 1981. That being so, one of the more meaningful sentences in the Queen's Speech will be the standard one at the end?Other measures will be placed before you. Under this blanket promise we can expect a Health Services (Miscellaneous Provisions) Bill. The point is that not having been promised specifically nobody can make political capital out of its non-appearance if time is found lacking. The Bill is expected to tidy up the rough edges left by lasr year's legislation on the reorganisation of the National Health Service and may tackle, among other things, the vexed problem of the registra tion of old people's homes. The major Bill from the DHSS will be a Social Security one carrying out the second stage of the reform of sickness benefit payments. The Government wants to shift responsibility for the first eight weeks of sick pay from the State to employers, which will mean a saving of some 5000 civil service jobs?a highly desirable end in these days of public spending cuts. The trouble is that many general practitioners are opposed to having to write sick notes for employers rather than for the DHSS. This is one of the most contentious issues in their relationship with the department and was not helped by the hope that under the new scheme they would continue to issue them free. While the Government may well be able to impose the new scheme on reluctant employers and unions, the co operation of GPs is essential since the scheme would fail without the provision of sick notes. GPs had seized on the proposed change as a chance to divest themselves of the whole time-consuming business, but negotia tions have led to a compromise proposal under which the issuing of sick notes would be removed from their terms of service. This would leave the way open for the profession to set its own level of charges, which could hardly be less than that for a prescription. Decisions have still to be taken, but the indications from the DHSS are that Ministers may be prepared to allow this concession in an attempt to buy the reluctant acquiescence of the doctors. There will also be a major Transport Bill, which will make the evidence of new and accurate breath-testing machines per missible in a court of law. The effect will be to speed up appear