tbuckley/cabot-search huggingface dataset:
Effects of Tamoxifen on Cardiovascular Risk Factors in Postmenopausal Women After 5 Years of Treatment
Authors: R. R. Love, D. A. Wiebe, J. M. Feyzi, P. A. Newcomb, R. J. Chappell
Journal: JNCI Journal of the National Cancer Institute (1994)

Adjuvant tamoxifen therapy for breast cancer has been given for a period of several years. Cardiovascular diseases increase in incidence rapidly in women older than 60 years. Favorable changes in cardiovascular risk factors have been seen with 2 years of tamoxifen therapy, and lower rates of myocardial infarction and of hospitalization for heart disease have been observed in tamoxifen-treated women. Purpose : We sought to evaluate changes in risk factors for cardiovascular diseases in postmenopausal women after therapy with tamoxifen for 5 years. Methods : Five years after their initial entry in a 2-year randomized, placebo-controlled toxicity study, we re-examined 62 of the original 140 disease-free, axillary node-negative post-menopausal breast cancer patients. These 62 patients were women available for study because they had not suffered major illness and had continued on either the tamoxifen or notamoxifen regimen to which they had been originally randomly assigned for the entire 5 years. Patient and control blood samples were analyzed for total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and sub-fractions, triglycerides, apolipoprotein AI, apolipoprotein B, lipoprotein(a), fibrinogen, glucose, and platelets. Results : At base line for all measurements except atherogenic lipoprotein [lipoprotein(a)] the 30 long-term tamoxifen recipients and the 32 long-term no-tamoxifen recipients were not significantly different. After 5 years, levels of total serum cholesterol ( P <.001), LDL cholesterol ( P <.0001), and lipoprotein(a) ( P =.001) were significantly lower, and apolipoprotein AI levels were significantly higher ( P <.001) in the tamoxifen-treated group compared with the no-tamoxifen group. Apolipoprotein B levels increased to a greater extent in the no-tamoxifen than in the tamoxifen group ( P <.001). After 5 years, fibrinogen level decreases and triglyceride level increases in the tamoxifen group compared with the notamoxifen group were of borderline statistical significance and HDL cholesterol levels were not different in the two groups. Conclusion : Favorable changes in lipid, lipoprotein, and fibrinogen levels seen early in tamoxifen therapy in postmenopausal women persist with treatment of 5 years. Implications : The types and magnitude of changes in cardiovascular risk factors seen here with tamoxifen are similar to a certain extent with those seen with estrogen supplements. Further risk-factor and ethnic-group data are needed to estimate the magnitude of expected benefits of tamoxifen treatment on incidence of heart disease.
Listing Occupational Carcinogens
Authors: Jack Siemiatycki, Lesley Richardson, Kurt Straif, Benoit Latreille, Ramzan Lakhani, Sally Campbell, Marie-Claude Rousseau, Paolo Boffetta
Journal: Environmental Health Perspectives (2004)

The occupational environment has been a most fruitful one for investigating the etiology of human cancer. Many recognized human carcinogens are occupational carcinogens. There is a large volume of epidemiologic and experimental data concerning cancer risks in different work environments. It is important to synthesize this information for both scientific and public health purposes. Various organizations and individuals have published lists of occupational carcinogens. However, such lists have been limited by unclear criteria for which recognized carcinogens should be considered occupational carcinogens, and by inconsistent and incomplete information on the occupations and industries in which the carcinogenic substances may be found and on their target sites of cancer. Based largely on the evaluations published by the International Agency for Research on Cancer, and augmented with additional information, the present article represents an attempt to summarize, in tabular form, current knowledge on occupational carcinogens, the occupations and industries in which they are found, and their target organs. We have considered 28 agents as definite occupational carcinogens, 27 agents as probable occupational carcinogens, and 113 agents as possible occupational carcinogens. These tables should be useful for regulatory or preventive purposes and for scientific purposes in research priority setting and in understanding carcinogenesis.
Allele-specific loss and transcription of the miR-15a/16-1 cluster in chronic lymphocytic leukemia
Authors: A Veronese, F Pepe, J Chiacchia, S Pagotto, P Lanuti, S Veschi, M Di Marco, A D'Argenio, I Innocenti, B Vannata, F Autore, M Marchisio, D Wernicke, F Verginelli, G Leone, L Z Rassenti, T J Kipps, R Mariani-Costantini, L Laurenti, C M Croce, R Visone
Journal: Leukemia (2014)

Deregulation of the miR-15a/16-1 cluster has a key role in the pathogenesis of chronic lymphocytic leukemia (CLL), a clinically heterogeneous disease with indolent and aggressive forms. The miR-15a/16-1 locus is located at 13q14, the most frequently deleted region in CLL. Starting from functional investigations of a rare SNP upstream the miR cluster, we identified a novel allele-specific mechanism that exploits a cryptic activator region to recruit the RNA polymerase III for miR-15a/16-1 transcription. This regulation of the miR-15a/16- locus is independent of the DLEU2 host gene, which is often transcribed monoallellically by RPII. We found that normally one allele of miR-15a/16-1 is transcribed by RNAPII, the other one by RNAPIII. In our subset of CLL patients harboring 13q14 deletions, exclusive RNA polymerase III (RPIII)-driven transcription of the miR-15a/16-1 was the consequence of loss of the RPII-regulated allele and correlated with high expression of the poor prognostic marker ZAP70 (P=0.019). Thus, our findings point to a novel biological process, characterized by double allele-specific transcriptional regulation of the miR-15a/16-1 locus by alternative mechanisms. Differential usage of these mechanisms may distinguish at onset aggressive from indolent forms of CLL. This provides a basis for the clinical heterogeneity of the CLL patients carrying 13q14 deletions.
The HMO Backlash — Righteous or Reactionary?
Authors: T Bodenheimer
Journal: New England Journal of Medicine (1996)

The membership of health maintenance organizations (HMOs) now exceeds 50 million people and may grow by an additional 50 million by the year 2000. But all is not well in HMO-land. An angry and determined backlash is spreading across the nation. In 1996 alone, 1000 pieces of legislation attempting to regulate or weaken HMOs were introduced in state legislatures, and 56 laws were passed in 35 states. The backlash movement brings together patients who complain of services denied and physicians who are suffering the loss of autonomy and income.1 There are several manifestations of the backlash: federal and state legislation, . . .
Lack of Effect of a Low-Fat, High-Fruit, -Vegetable, and -Fiber Diet on Serum Prostate-Specific Antigen of Men Without Prostate Cancer: Results From a Randomized Trial
Authors: Moshe Shike, Lianne Latkany, Elyn Riedel, Martin Fleisher, Arthur Schatzkin, Elaine Lanza, Donald Corle, Colin B. Begg
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To determine whether a diet low in fat and high in fruits, vegetables, and fiber may be protective against prostate cancer by having an impact on serial levels of serum prostate-specific antigen (PSA). METHODS: Six hundred eighty-nine men were randomized to the intervention arm and 661 to the control arm. The intervention group received intensive counseling to consume a diet low in fat and high in fiber, fruits, and vegetables. The control group received a standard brochure on a healthy diet. PSA in serum was measured at baseline and annually thereafter for 4 years, and newly diagnosed prostate cancers were recorded. RESULTS: The individual PSA slope for each participant was calculated, and the distributions of slopes were compared between the two groups. There was no significant difference in distributions of the slopes (P = .99). The two groups were identical in the proportions of participants with elevated PSA at each time point. There was no difference in the PSA slopes between the two groups (P = .34) and in the frequencies of elevated PSA values for those with elevated PSA at baseline. Incidence of prostate cancer during the 4 years was similar in the two groups (19 and 22 in the control and intervention arms, respectively). CONCLUSION: Dietary intervention over a 4-year period with reduced fat and increased consumption of fruits, vegetables, and fiber has no impact on serum PSA levels in men. The study also offers no evidence that this dietary intervention over a 4-year period affects the incidence of prostate cancer during the 4 years.
Treatment of Fibromyalgia Syndrome With Antidepressants
Authors: Winfried Häuser, Kathrin Bernardy, Nurcan Üçeyler, Claudia Sommer
Journal: JAMA (2009)

Fibromyalgia syndrome (FMS) is a chronic pain disorder associated with multiple debilitating symptoms and high disease-related costs. Effective treatment options are needed.To determine the efficacy of antidepressants in the treatment of FMS by performing a meta-analysis of randomized controlled clinical trials.MEDLINE, PsycINFO, Scopus, and the Cochrane Library databases were searched through August 2008. Reference sections of original studies, meta-analyses, and reviews on antidepressants in FMS were reviewed.Randomized placebo-controlled trials with tricyclic and tetracyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), and monoamine oxidase inhibitors (MAOIs) were analyzed.Two authors independently extracted data. Effects were summarized using standardized mean differences (SMDs) by a random-effects model.Eighteen randomized controlled trials (median duration, 8 weeks; range, 4-28 weeks) involving 1427 participants were included. Overall, there was strong evidence for an association of antidepressants with reduction in pain (SMD, -0.43; 95% confidence interval [CI], -0.55 to -0.30), fatigue (SMD, -0.13; 95% CI, -0.26 to -0.01), depressed mood (SMD, -0.26; 95% CI, -0.39 to -0.12), and sleep disturbances (SMD, -0.32; 95% CI, -0.46 to -0.18). There was strong evidence for an association of antidepressants with improved health-related quality of life (SMD, -0.31; 95% CI, -0.42 to -0.20). Effect sizes for pain reduction were large for TCAs (SMD, -1.64; 95% CI, -2.57 to -0.71), medium for MAOIs (SMD, -0.54; 95% CI, -1.02 to -0.07), and small for SSRIs (SMD, -0.39; 95% CI, -0.77 to -0.01) and SNRIs (SMD, -0.36; 95% CI, -0.46 to -0.25).Antidepressant medications are associated with improvements in pain, depression, fatigue, sleep disturbances, and health-related quality of life in patients with FMS.
James Fleming McHarg
Authors: P. Aungle
Journal: BMJ (2003)

Former consultant psychiatrist and honorary senior lecturer Dundee (b 1917; q Edinburgh 1940; MD, FRCP Ed, FRCPsych), died from endocarditis on 10 March 2003.​2003.




Figure 1




James McHarg's medical career began in the Royal Navy, where he achieved the rank of surgeon commander. In civilian life he trained at the Royal Edinburgh Hospital, and thence moved to Gartnavel Royal Hospital in Glasgow as deputy physician superintendent before coming to his final post in Dundee. His special clinical interests included neuropsychiatric syndromes, affective disorder in children (he published a valuable paper on childhood mania), and Jungian psychopathology. Jungian concepts led him to a close study of cases of paranormal phenomena.
Epigenetic Regulation of Pluripotency and Differentiation
Authors: Michael J. Boland, Kristopher L. Nazor, Jeanne F. Loring
Journal: Circulation Research (2014)

The precise, temporal order of gene expression during development is critical to ensure proper lineage commitment, cell fate determination, and ultimately, organogenesis. Epigenetic regulation of chromatin structure is fundamental to the activation or repression of genes during embryonic development. In recent years, there has been an explosion of research relating to various modes of epigenetic regulation, such as DNA methylation, post-translational histone tail modifications, noncoding RNA control of chromatin structure, and nucleosome remodeling. Technological advances in genome-wide epigenetic profiling and pluripotent stem cell differentiation have been primary drivers for elucidating the epigenetic control of cellular identity during development and nuclear reprogramming. Not only do epigenetic mechanisms regulate transcriptional states in a cell-type–specific manner but also they establish higher order genomic topology and nuclear architecture. Here, we review the epigenetic control of pluripotency and changes associated with pluripotent stem cell differentiation. We focus on DNA methylation, DNA demethylation, and common histone tail modifications. Finally, we briefly discuss epigenetic heterogeneity among pluripotent stem cell lines and the influence of epigenetic patterns on genome topology.
Orphan drugs and the NHS
Authors: Mark Sheehan
Journal: BMJ (2005)

Improving surveillance of MRSA bacteraemiaData from north west England support Oxfordshire findings Editor-Wyllie et al conclude that admission cultures accounted for 24% of total hospital methicillin resistant Staphylococcus aureus (MRSA) bacteraemia episodes over seven years to March 2004. 1 Data collected from five district general hospitals and one university hospital in Cheshire and Merseyside and one district general hospital in greater Manchester support this view.This group of hospitals has collected enhanced MRSA bacteraemia surveillance data using published case definitions from the Department of Health since April 2004.Anonymised data are collected on paper forms and analysed using the FORMIC data capture system.In all, 534 cases of S aureus bacteraemia were identified between April 2004 and March 2005, 334 being methicillin sensitive S aureus bacteraemia and 200 MRSA bacteraemia.Sixty six of the MRSA bacteraemia cases occurred within 48 hours of arrival in hospital, 16 being related to a previous hospital admission, 25 in patients known to have been colonised with MRSA, and 13 in patients admitted from nursing or residential homes.Thirty five cases were admitted as medical specialties, 25 of them in patients over 65.Our results support the suggestion by Wyllie et al that anti-MRSA treatment should be considered for patients with possible staphylococcal sepsis who have previously been admitted or known to be colonised with MRSA.In a predominantly district general hospital setting, anti-MRSA treatment should also be considered for possible staphylococcal sepsis in elderly medical admissions and admissions from nursing homes.
Lessons of the Coronary-Bypass Debate
Authors: Howard H. Hiatt
Journal: New England Journal of Medicine (1977)

A widely prevalent disease that is uniformly fatal in outcome and often devastating in manifestations presents an ideal circumstance for the ready acceptance of a promising treatment. If the treatment cures almost all patients within weeks, it rapidly becomes a part of medical practice. This was the sequence observed, for example, after the introduction of antibiotic therapy of subacute bacterial endocarditis and of a host of other serious infections. When, however, treatment does not lead to speedy and uniform improvement, and particularly when the expressions of the disease in question are subject to inexplicable remissions and exacerbations, we in medicine . . .
Cl. Welchii Infection following Abortion
Authors: R. Y. Dawbarn, B. Williams
Journal: BMJ (1938)

t MEDIC&BRTRH 2AL 79 hvlp to encourage the use of our radiological clinic.This, in brief, illustrates the procedure I have adopted for over fifteen years.Conclusion Medical practitioners are gradually recognizing the help that chest skiagraphy can give, but they sometimes have difficulty in obtaining a patient's consent to undergo exam- ination.This reluctance is usually related to the popular idea that tubercCUlosis is necessarily incurable.The wise and tactful practitioner will explain that the object of skiagraphy is to make sure that the patient is all right, or at least only suffering from disease in an early stage.Driving and other tests are becoming more common among the general public, and a few minutes' simple explanation will often reassure a timid patient.Skiagraphy of the chest is so important for accurate diagnosis that it can seldom be omitted with safety.It is the most valuable single factor in the diagnosis of pulmonary disease.
Differential contribution of hepatitis C virus NS5A and core proteins to the induction of oxidative and nitrosative stress in human hepatocyte-derived cells
Authors: María Victoria García-Mediavilla, Sonia Sánchez-Campos, Pilar González-Pérez, Marta Gómez-Gonzalo, Pedro Lorenzo Majano, Manuel López-Cabrera, Gerardo Clemente, Carmelo García-Monzón, Javier González-Gallego
Journal: Journal of Hepatology (2005)
ULTRAFILTRABLE MAGNESIUM IN HYPERTHYROIDISM
Authors: Louis J. Soffer, D. Alfred Dantes, Edward B. Grossman, Harry Sobotka, Mildred D. Jacobs
Journal: Journal of Clinical Investigation (1939)

The following report is concerned with the study of magnesium metabolism in clinical and experimental hyperthyroidism.This first com- munication deals primarily with the ratio of diffusible magnesium to total serum magnesium in the hyperthyroid state.The general question of relationship of total serum magnesium to its ultrafiltrable fraction in 8 normal individuals has been discussed by Watchorn and McCance (1).They found that normally approximately 25 per cent of the total serum magnesium is non-diffusible.These authors suggest that there are probably 2 factors which play a part in determining the amount of ionizable magnesium.The bound magnesium may be in combination either with the protein in the serum or with the serum phosphatides.These acids, which behave similarly to protein, are pres- ent in adequate quantities to bind considerable amounts of magnesium.Brull (2) and Scholtz (3) also believe that both calcium and magnesium form colloidal phosphate complexes. METHODThe total serum magnesium was determined by the method of Briggs (4).The serum proteins were precipitated with trichloracetic acid.It was found that little, if any, magnesium was carried down with the protein flocculum.To 10 cc. of protein free filtrate were added 1 cc. of 20 per cent sodium acetate, 6 to 8 drops of 0.016 per cent bromcresol green, and 1 cc. of 4 per cent ammonium oxalate.The pH of the solution was adjusted to 5.0 by addition of ammonium hydrox- ide.The mixture was allowed to stand overnight, and the precipitated calcium oxalate then separated by centrifugation.To the decanted supernatant fluid and washings were added 1 cc. of 2 per cent potassium dihydrogen phosphate,
A Functional IL-13 Receptor is Expressed on Polarized Murine CD4 + Th17 Cells and IL-13 Signaling Negatively Regulates Th17 Cytokine Production
Authors: D.C. Newcomb, W. Zhou, M.L. Moore, K. Goleniewska, G.K.K. Hershey, J.K. Kolls, R.S. Peebles Jr
Journal: Journal of Allergy and Clinical Immunology (2009)
Making the Best of Hospital Pay for Performance
Authors: Andrew Ryan, Jan Blustein
Journal: New England Journal of Medicine (2012)

Interview with Dr. Jan Blustein on the effects of pay-for-performance approaches for hospitals. (08:03)Download In October, U.S. acute care hospitals will begin to be "paid for performance" under the Medicare Hospital Value-Based Purchasing program. But accumulating evidence raises doubts about whether the program will in fact improve value. What can be done to redirect the policy?
KITENIN-targeting MicroRNA-124 Suppresses Colorectal Cancer Cell Motility and Tumorigenesis
Authors: So-Yeon Park, Hangun Kim, Somy Yoon, Jeong A Bae, Seok-Yong Choi, Young Do Jung, Kyung Keun Kim
Journal: Molecular Therapy (2014)

MicroRNAs are increasingly implicated in the modulation of the progression of various cancers. We previously observed that KAI1 C-terminal interacting tetraspanin (KITENIN) is highly expressed in sporadic human colorectal cancer (CRC) tissues and hence the functional KITENIN complex acts to promote progression of CRC. However, it remains unknown that microRNAs target KITENIN and whether KITENIN-targeting microRNAs modulate CRC cell motility and colorectal tumorigenesis. Here, through bioinformatic analyses and functional studies, we showed that miR-124, miR-27a, and miR-30b negatively regulate KITENIN expression and suppress the migration and invasion of several CRC cell lines via modulation of KITENIN expression. Through in vitro and in vivo induction of mature microRNAs using a tetracycline-inducible system, miR-124 was found to effectively inhibit the invasion of CT-26 colon adenocarcinoma cells and tumor growth in a syngeneic mouse xenograft model. Constitutive overexpression of precursor miR-124 in CT-26 cells suppressed in vivo tumorigenicity and resulted in decreased expression of KITENIN as well as that of MYH9 and SOX9, which are targets of miR-124. Thus, our findings identify that KITENIN-targeting miR-124, miR-27a, and miR-30b function as endogenous inhibitors of CRC cell motility and demonstrate that miR-124 among KITENIN-targeting microRNAs plays a suppressor role in colorectal tumorigenesis. MicroRNAs are increasingly implicated in the modulation of the progression of various cancers. We previously observed that KAI1 C-terminal interacting tetraspanin (KITENIN) is highly expressed in sporadic human colorectal cancer (CRC) tissues and hence the functional KITENIN complex acts to promote progression of CRC. However, it remains unknown that microRNAs target KITENIN and whether KITENIN-targeting microRNAs modulate CRC cell motility and colorectal tumorigenesis. Here, through bioinformatic analyses and functional studies, we showed that miR-124, miR-27a, and miR-30b negatively regulate KITENIN expression and suppress the migration and invasion of several CRC cell lines via modulation of KITENIN expression. Through in vitro and in vivo induction of mature microRNAs using a tetracycline-inducible system, miR-124 was found to effectively inhibit the invasion of CT-26 colon adenocarcinoma cells and tumor growth in a syngeneic mouse xenograft model. Constitutive overexpression of precursor miR-124 in CT-26 cells suppressed in vivo tumorigenicity and resulted in decreased expression of KITENIN as well as that of MYH9 and SOX9, which are targets of miR-124. Thus, our findings identify that KITENIN-targeting miR-124, miR-27a, and miR-30b function as endogenous inhibitors of CRC cell motility and demonstrate that miR-124 among KITENIN-targeting microRNAs plays a suppressor role in colorectal tumorigenesis.
The Government and Selective Nontreatment of Handicapped Infants
Authors: Robert F. Weir
Journal: New England Journal of Medicine (1983)

ON April 9, 1982, a baby known only as "Infant Doe" was born in Bloomington, Indiana. He had Down's syndrome, plus esophageal atresia with associated tracheoesophageal fistula. Over the course of six days, he became the focal point of an intensive medical, legal, and ethical debate. When the parents chose to withhold surgery and intravenous feeding, the hospital administrators sought legal advice on the case. The ensuing legal battle involved several lower-court hearings, an informal hearing by the Indiana Supreme Court, and a trip to Washington, D.C., by Bloomington prosecutors to secure an emergency stay of the Indiana court orders, . . .