tbuckley/cabot-search huggingface dataset:
A Prospective Study of Cigarette Smoking and Risk of Cataract in Men
Authors: William G. Christen
Journal: JAMA (1992)

<h3>Objective.</h3> —To examine the association between cigarette smoking and the incidence of cataract. <h3>Design, Setting, and Participants.</h3> —The design was a prospective cohort study using data from the Physicians' Health Study, a randomized trial of aspirin and beta carotene among 22 071 US male physicians aged 40 to 84 years that began in 1982. This analysis includes the 17 824 physicians who did not report cataract at baseline and did provide complete risk factor information. Based on information reported at baseline, 10% were current smokers, 39% were past smokers, and 51% were never smokers. <h3>Main Outcome Measure.</h3> —An<i>incident cataract</i>was defined as a self-report confirmed by medical record review to have been first diagnosed after randomization, age-related in origin, and responsible for a decrease in best corrected visual acuity to 20/30 or worse. <h3>Main Results.</h3> —During 60 months of follow-up, 557 incident cataracts among 371 participants were confirmed. Compared with never smokers, current smokers of 20 or more cigarettes per day had a statistically significant increase in the risk of cataract (relative risk [RR], 2.16; 95% confidence interval [Cl], 1.46 to 3.20;<i>P</i>&lt;.001). Similar results were obtained after simultaneously controlling for other potential cataract risk factors in a logistic regression model (RR, 2.05; 95% Cl, 1.38 to 3.05;<i>P</i>&lt;.001). Among the 557 eyes with cataract, nuclear sclerotic changes were present in 442 while posterior subcapsular changes were present in 204. After controlling for other potential cataract risk factors, current smokers of 20 or more cigarettes per day had statistically significant increases in nuclear sclerosis (RR, 2.24; 95% Cl, 1.47 to 3.41;<i>P</i>&lt;.001) and posterior subcapsular (RR, 3.17; 95% Cl, 1.81 to 5.53;<i>P</i>&lt;.001) cataract. Past smokers had an elevated risk of posterior subcapsular (RR, 1.44; 95% Cl, 0.97 to 2.13;<i>P</i>=.07) but not nuclear sclerosis cataract. For current smokers of fewer than 20 cigarettes per day, no increased risks were observed of total, nuclear sclerosis, or posterior subcapsular cataract. <h3>Conclusions.</h3> —These data provide support for the hypothesis that cigarette smoking increases the risk of developing both nuclear sclerosis and posterior subcapsular cataract. (<i>JAMA</i>. 1992;268:989-993)
Abstract 321: Sunitinib alternated with everolimus in renal cell carcinoma: a sequential combination strategy for antitumor efficacy in mice clinical trial.
Authors: Célia Dos Santos, Annemilaï Tijeras-Raballand, Maria Serova, Chantal Dreyer, Khemaies Slimane, Armand de Gramont, Sandrine Faivre, Eric Raymond
Journal: Cancer Research (2013)

Abstract Background: Sunitinib (VEGFR/PDGFR inhibitor) and everolimus (mTOR inhibitor) are approved for advanced renal cell carcinoma (RCC), as first-line and second-line therapy, respectively. No data have been reported on programmed sequential strategies combining alternative use of sunitinib and everolimus prior to progression. Such strategy is expected to delay the emergence of first-line acquired resistance and improve tumor control. The aim of our study was to assess the effects of three sequences administration of sunitinib and everolimus. Methods: Nude mice (n=5/group) were engrafted with human RCC cells (CAKI-1) then randomized to vehicle, everolimus, sunitinib, sunitinib alternated with everolimus every week (S1), every two weeks (S2), and every three weeks (S3). Median time to tumor progression (mTTP) was determined in each group. Angiogenesis and necrosis were evaluated using CD31 and HE staining. Inhibition of mTOR pathway was evaluated using phospho-S6 (pS6) and e-cadherin/vimentin expressions were analyzed by immunofluorescence staining. Results: The S1, S2 and S3 regimens increased mTTP by 30 to 80% relative to sunitinib or everolimus alone. The vascular surface areas (vessels size and number) in tumors were reduced in all treated groups relative to control, especially S1 and S2. All three sequential therapies induced larger necrosis areas in tumors as compared to control. In each group, tumor response seemed associated with a decrease in pS6 expression and changes in epithelial-mesenchymal phenotype with a decrease in vimentin and an increase in e-cadherin expression Conclusion: Sunitinib and everolimus programmed sequential regimens prior to progression yielded longer mTTP than sunitinib and everolimus monotherapies. The sequential combinations of these two agents in a RCC mouse clinical trial, increased antiangiogenic effects, leading potentially to tumor necrosis, especially with the S1 and S2 regimens. mTTP for each group and effects of sequential treatments in tumors angiogenesis and necrosis Treatment groups mTTP (in days) Vascular Surface Area per field (% vs control) Number of vessels per field % of necrosis surface per field Control 24 100 22 23 Sunitinib 36 30 5 47 Everolimus 50 28 7 27 S1 64 15 5 37 S2 59 20 4 51 S3 59 42 5 37 Citation Format: Célia Dos Santos, Annemilaï Tijeras-Raballand, Maria Serova, Chantal Dreyer, Khemaies Slimane, Armand de Gramont, Sandrine Faivre, Eric Raymond. Sunitinib alternated with everolimus in renal cell carcinoma: a sequential combination strategy for antitumor efficacy in mice clinical trial. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 321. doi:10.1158/1538-7445.AM2013-321
Letter: New look at monoamine oxidase inhibitors.
Authors: W Sargant
Journal: BMJ (1976)

in its longest diameter was the only lesion detected.No evidence was found by which the latter could be aetiologically linked to the hydrops.In particular, there were no "vuln- erable" blood vessels of the placenta that might have been obstructed by the tumour, nor was this excessively vascular, so that an arteriovenous shunt effect was unlikely.Explanations such as protein sequestration by the tumour or unduly rapid increase in the vascular bed are within the realms of speculation.This association has not been reported before so far as I am aware (although Macafee et al; mention a case of mediastinal teratoma associated with hydrops) and I should be grateful to hear from any of your readers who know of a similar observation.
Developmental Pattern of a Serum Binding Protein for Multiplication Stimulating Activity in the Rat
Authors: Robert M. White, S. Peter Nissley, Patricia A. Short, Matthew M. Rechler, Ilene Fennoy
Journal: Journal of Clinical Investigation (1982)

The concentration of multiplication stimulating activity (MSA), an insulinlike growth factor (IGF), is high in fetal rat serum. We now report that MSA is exclusively associated wth an albumin-size binding protein in fetal rat serum; the growth hormone-dependent, gamma globulin-size binding protein, which predominates in the older animal, is absent from fetal rat serum. When (125)I-MSA was incubated with fetal rat serum and then gel filtered on Sephadex G-200, specific radioactivity eluted in the void volume (peak I) and the albumin region (peak III); by contrast, specific radioactivity eluted mainly in the gamma globulin region (peak II) in adult rat serum. Pools of the Sephadex G-200 fractions were chromatographed on Sephadex G-50, in 1 M acetic acid, to separate the binding protein from IGF activity. Analysis of IGF activity by chick embryo fibroblast bioassay, competitive protein binding assay, and MSA by radioimmunoassay revealed that all the IGF activity and MSA in fetal rat serum resided in peak III. Measurement of MSA binding capacity of the stripped binding protein by Scatchard analysis demonstrated that the majority of binding capacity also was found in peak III in fetal rat serum; most of MSA binding capacity was in peak II in adult rat serum. In fetal rat sera, in addition to the peak III binding protein, which is the major carrier of endogenous MSA, there is a component in peak I capable of specifically binding (125)I-MSA. This component elutes as a single species from a Sepharose-6B column. As MSA associated with peak III gradually declined in early neonatal life, peak II-associated IGF activity measured by chick embryo fibroblast bioassay showed a rise of activity with a peak at 5 d of neonatal life, a nadir at 20 d, with an increase again to attain adult levels. These studies demonstrate that the MSA binding protein in the fetus is different from the growth hormone-dependent binding protein in adult life.
The portocaval shunt rat as a model to study pharmacokinetics in cirrhosis: Propranolol and its glucuronides
Authors: U. Baumqartner, E. Stahl, H. Spahn-Lanqquth, D. Krauss, E. Mutschler, E.H. Farthmann, J. Schölaerich
Journal: Journal of Hepatology (1990)
Multiple actions of systemic artemin in experimental neuropathy
Authors: Luis R Gardell, Ruizhong Wang, Chris Ehrenfels, Michael H Ossipov, Anthony J Rossomando, Stephan Miller, Carolyn Buckley, Amber K Cai, Albert Tse, Susan F Foley, BangJian Gong, Lee Walus, Paul Carmillo, Dane Worley, Carol Huang, Thomas Engber, Blake Pepinsky, Richard L Cate, Todd W Vanderah, Josephine Lai, Dinah W Y Sah, Frank Porreca
Journal: Nature Medicine (2003)
Persistent Blood-giving
Authors: E. M. Biske
Journal: BMJ (1942)

In spite of the recognition that striatal D<sub>2</sub> receptors are critical determinants in a variety of psychomotor disorders, the cellular mechanisms by which these receptors shape neuronal activity have remained a mystery. The studies presented here reveal that D<sub>2</sub> receptor stimulation in enkephalin-expressing medium spiny neurons suppresses transmembrane Ca<sup>2+</sup> currents through L-type Ca<sup>2+</sup> channels, resulting in diminished excitability. This modulation is mediated by G<sub>β</sub><sub>γ</sub> activation of phospholipase C, mobilization of intracellular Ca<sup>2+</sup> stores, and activation of the calcium-dependent phosphatase calcineurin. In addition to providing a unifying mechanism to explain the apparently divergent effects of D<sub>2</sub> receptors in striatal medium spiny neurons, this novel signaling linkage provides a foundation for understanding how this pivotal receptor shapes striatal excitability and gene expression.
Squeeze on NHS has not yet resulted in worse care, report says
Authors: N. Hawkes
Journal: BMJ (2013)

The quality of care in the NHS in England is being sustained despite the drive for efficiency savings, the Nuffield Trust and the Health Foundation have found in a joint programme of research. But despite this reassuring conclusion they say that more could be done to reduce the number of emergency admissions to hospital, especially of older people.

The findings are the first to come from a collaboration between the two organisations, which plan over the next five years to keep a scorecard of quality in the NHS, assessing whether it is improving, stable, or declining by evaluating almost 150 quality indicators that cover the whole spectrum of health and social care. The programme, QualityWatch, will examine access, safety, effectiveness, …
Harm resulting from screening is likely to be high where prevalence of breast cancer is low
Authors: P. Adab
Journal: BMJ (1997)

Editor—Matti Hakama and colleagues evaluated an organised programme of screening for breast cancer in Finland.1 They report a 24% reduction in mortality from breast cancer due to screening, which, as they point out, is close to the protective effect reported in the early randomised controlled trials. In their …
Superior Vena Cava Syndrome
Authors: R G Kovacs, S M Aguayo
Journal: New England Journal of Medicine (1993)

Figure 1. Superior Vena Cava Syndrome. The photograph shows massive engorgement of collateral subcutaneous veins of the chest and abdomen in a 58-year-old man with partial obstruction of the superior vena cava caused by small-cell lung cancer. The patient also had distended neck veins but minimal facial edema. The venous dilatation improved transiently with radiation therapy. The patient died several weeks after the photograph was taken.
HODGKIN'S DISEASE IN BROTHERS
Authors: W. Kenneth Jennings
Journal: JAMA (1934)

<h3>To the Editor:—</h3> InThe Journal, February 17, McHeffey and Peterson reported two cases of Hodgkin's disease occurring simultaneously in brothers. Reference was made to the rarity in which this condition occurs in more than one member of a family. I wish to report another instance of two cases occurring in brothers: A. C., a man, aged 32, came to the surgical dispensary at Northwestern University Medical School, April 13, 1931, complaining of a swelling in the right axilla of one year's duration. Examination at that time revealed several indurated discrete axillary nodes. There was moderate enlargement of the spleen. The blood count indicated 6,125 white blood cells, with a normal differential count save for 3 per cent eosinophils, and 4,760,000 red blood cells with 85 per cent hemoglobin. The patient stated that a biopsy had been made three months previously at Epworth Hospital, South Bend, Ind. A laboratory report
The Definition of Anemia in Older Persons
Authors: Gerbrand J. Izaks
Journal: JAMA (1999)

ContextWhether hemoglobin concentrations defined as anemia by the World Health Organization (WHO) are associated with increased mortality in older persons is not known.ObjectiveTo investigate the association between hemoglobin concentration and cause-specific mortality in older persons.DesignCommunity-based study conducted from 1986 to 1996 (follow-up period, 10 years).SettingLeiden, the Netherlands.ParticipantsA total of 1016 community residents aged 85 years and older were eligible and 872 agreed to have a blood sample taken. Hemoglobin concentration was measured in 755 persons (74%).Main Outcome MeasuresHemoglobin concentration, 10-year survival, and primary cause of death. According to the WHO criteria, anemia was defined as a hemoglobin concentration below 7.5 mmol/L (120 g/L) in women and below 8.1 mmol/L (130 g/L) in men.ResultsCompared with persons with a normal hemoglobin concentration, the mortality risk was 1.60 (95% confidence interval [CI], 1.24-2.06; P&lt;.001) in women with anemia, and 2.29 (95% CI, 1.60-3.26; P&lt;.001) in men with anemia. In both sexes, the mortality risk increased with lower hemoglobin concentrations. In persons without self-reported clinical disease at baseline, the mortality risk of anemia was 2.21 (95% CI, 1.37-3.57; P=.002). Mortality from malignant and infectious diseases was higher in persons with anemia.ConclusionsAnemia defined by the WHO criteria was associated with an increased mortality risk in persons aged 85 years and older. The criteria are thus appropriate for older persons. A low hemoglobin concentration at old age signifies disease.
Not made to measure
Authors: A. Liston
Journal: BMJ (2001)

Today I was late for the primary care group (PCG) board meeting. After morning surgery there had been the usual rush of paperwork, telephone calls, and the mad dash round my house calls. The final call was a visit to an elderly man whose wife had died two days before. She had become ill while I had been away on a course (on evidence based practice) and had been attended by one of my colleagues. Her heart failure had not responded to treatment and she needed admission to hospital, where she died the next day.

> Is there an evidence base for the efficacy of bereavement visits and, if so, who is best placed to provide them? 

My colleague had told me of the concern the couple had expressed that their usual doctor had been unable to attend. His thoughtful follow up phone call to ask if the widower would appreciate a house call met with a request for his “usual doctor” to call—“if that was all right.”

When at first there was no response …
Circulating transforming growth factor β1 and coronary artery disease
Authors: X Wang
Journal: Cardiovascular Research (1997)

Objective: Transforming growth factor β1 (TGF-β1), a multifunctional cytokine, is involved in many physiological and pathological processes and possibly in atherogenesis. Methods: We explored the association between circulating plasma TGF-β1 measured by ELISA and coronary artery disease (CAD) assessed angiographically in 371 Caucasian patients (269 men and 102 women) aged ≤65 years. Results: While mean±s.e.m. total TGF-β1 was not different among patients with (56.9±1.5 ng/ml) or without (54.6±2.8 ng/ml) angiographically demonstrable CAD, naturally active TGF-β1 was significantly higher in CAD patients (1.74±0.18 vs 0.96±0.17 ng/ml, P<0.01). Active TGF-β1 increased with the number of major coronary arteries with more than 50% luminal obstruction (P<0.01), and patients with triple vessel disease had twice the level of those with no or mild vessel disease (2.15±0.46 vs 1.12±0.14 ng/ml, P<0.001). We found no relationship between TGF-β1 and Lp(a), but TGF-β1 was significantly correlated with circulating fibrinogen (r=0.178, P=0.005) and fasting glucose (r=0.177, P=0.007) levels. Conclusions: Our study identifies an increase in active TGF-β1 levels with both the occurrence and severity of CAD which is independent of standard CAD risk factors. This may reflect a 'double-edged sword' effect of TGF-β1 in that it may reduce atherogenesis by inhibiting smooth muscle cell proliferation but, when there is ongoing vessel wall injury, enhance it by promoting excessive extracellular matrix accumulation. The outcome could represent a complex balance between these two competing influences.
Tools Available for Health Care Providers Whose Patients Are at Risk for Domestic Violence
Authors: Teri Randall
Journal: JAMA (1991)

HEALTH CARE providers may be the first and only professionals in a position to recognize violence in their patients' lives. Physicians are advised to routinely discuss the problem of domestic violence with their female patients and make available written material with resource information. <h3>Resources for Patients</h3> The Michigan Coalition Against Domestic Violence provides information packets to health care providers nationwide that include brochures and stickers for use in the office. Physicians who use these materials say they cannot keep enough on hand. All the materials may be reproduced. (Write the Michigan Coalition Against Domestic Violence, PO Box 463100, Mount Clemens, MI 48046, or telephone (313) 954-1180.) The best place to display the brochures is in the examination room, and not the lobby, says Sherrie Eisele, advocate/volunteer coordinator for Woman-Kind. If the brochures are in the lobby, Eisele explains, the woman has to "walk across the room and pick up a
Long-QT mutation p.K557E-Kv7.1: dominant-negative suppression of IKs, but preserved cAMP-dependent up-regulation
Authors: Roel L.H.M.G. Spätjens, Markéta Bébarová, Sandrine R.M. Seyen, Viola Lentink, Roselie J. Jongbloed, Yvonne H.J.M. Arens, Jordi Heijman, Paul G.A. Volders
Journal: Cardiovascular Research (2014)

Mutations in KCNQ1, encoding for Kv7.1, the α-subunit of the IKs channel, cause long-QT syndrome type 1, potentially predisposing patients to ventricular tachyarrhythmias and sudden cardiac death, in particular, during elevated sympathetic tone. Here, we aim at characterizing the p.Lys557Glu (K557E) Kv7.1 mutation, identified in a Dutch kindred, at baseline and during (mimicked) increased adrenergic tone. K557E carriers had moderate QTc prolongation that augmented significantly during exercise. IKs characteristics were determined after co-expressing Kv7.1-wild-type (WT) and/or K557E with minK and Yotiao in Chinese hamster ovary cells. K557E caused IKs loss of function with slowing of the activation kinetics, acceleration of deactivation kinetics, and a rightward shift of voltage-dependent activation. Together, these contributed to a dominant-negative reduction in IKs density. Confocal microscopy and western blot indicated that trafficking of K557E channels was not impaired. Stimulation of WT IKs by 3′-5′-cyclic adenosine monophosphate (cAMP) generated strong current up-regulation that was preserved for K557E in both hetero- and homozygosis. Accumulation of IKs at fast rates occurred both in WT and in K557E, but was blunted in the latter. In a computational model, K557E showed a loss of action potential shortening during β-adrenergic stimulation, in accordance with the lack of QT shortening during exercise in patients. K557E causes IKs loss of function with reduced fast rate-dependent current accumulation. cAMP-dependent stimulation of mutant IKs is preserved, but incapable of fully compensating for the baseline current reduction, explaining the long QT intervals at baseline and the abnormal QT accommodation during exercise in affected patients.
ATRIAL TACHYARRHYTHMIAS AS A MANIFESTATION OF ORALLY ACQUIRED ACUTE CHAGAS DISEASE
Authors: Ivan Mendoza, Juan Marques, Mendoza M. Ivan, Belkisyole Alarcon, Francesca Misticchio, Federico Moleiro, Alvaro Matheus, Jaime Torres, Oscar Noya
Journal: Journal of the American College of Cardiology (2011)
Non-Mendelian Inheritance of Paralogs of 2 Cytoskeletal Genes in the Ciliate Chilodonella uncinata
Authors: T. Robinson, L. A. Katz
Journal: Molecular Biology and Evolution (2007)

Recognition of the role of non-Mendelian inheritance is on the rise, particularly as epigenetic phenomena are shown to shape the transformation of genomes into phenotypes. Ciliates provide a model system in which to explore the role of epigenetics because ciliates have both a germ line (micronuclear) and somatic (macronuclear) genome within every cell. In the ciliate Chilodonella uncinata, the macronucleus is extensively fragmented such that many genes end up on their own chromosomes. Hence, it is possible to track the fate of unlinked genes within macronuclei of C. uncinata. Here we demonstrate that the pattern of inheritance in isolates of C. uncinata is complex and involves both Mendelian transmission between micronuclei and macronuclei and epigenetic phenomena. The macronuclei from 2 isolates of C. uncinata and their progeny share identical rDNA loci and 2 identical beta-tubulin paralogs, yet have different actin paralogs and some beta-tubulin paralogs that are not shared. We propose a model in which all the divergent paralogs are present in the ciliate micronuclei. Under this model, different paralogs are retained in developing macronuclei following conjugation. We further speculate that an epigenetic mechanism, such as RNA interference, is involved in selective retention of specific paralogs within lines. This system allows the exploration of epigenetic phenomena that shape somatic genomes and provides parallels to studies of the development of somatic nuclei within animals.
Recombinant adeno-associated viral vectors as therapeutic agents to treat neurological disorders
Authors: Ronald J. Mandel, Fredric P. Manfredsson, Kevin D. Foust, Aaron Rising, Sharon Reimsnider, Kevin Nash, Corinna Burger
Journal: Molecular Therapy (2006)

Recombinant adeno-associated virus (rAAV) is derived from a small human parvovirus with an excellent safety profile. In addition, this viral vector efficiently transduces and supports long-term transgene expression in the nervous system. These properties make rAAV a reasonable candidate vector for treating neurological disorders. Indeed, rAAV is currently being used in five early stage clinical trials for various neurodegenerative disorders. Therefore, we will review the currently available preclinical data using rAAV in animal models of central nervous system (CNS) disorders. Moreover, potential caveats for rAAV-based gene therapy in the CNS are also presented.
THE CONTRIBUTION OF RENAL FAILURE AND DIABETES MELLITUS TO THE PROGNOSIS OF PATIENTS WITH ACUTE MYOCARDIAL INFARCTION UNDERGOING PERCUTANEOUS CORONARY INTERVENTION
Authors: Manuel A. Gonzalez, Sara D. Collins, Itsik Ben-Dor, Gabriel Maluenda, Asmir I. Syed, Michael A. Gaglia, Zhenyi Xue, Cedric Delhaye, Kohei Wakabayashi, Nicholas N. Hanna, Rebecca Torguson, William O. Suddath, Kenneth M. Kent, Joseph Lindsay, Augusto D. Pichard, Lowell F. Satler, Ron Waksman
Journal: Journal of the American College of Cardiology (2010)