tbuckley/cabot-search huggingface dataset:
Genetic variants in telomerase-related genes are associated with an older age at diagnosis in glioma patients: evidence for distinct pathways of gliomagenesis
Authors: K. M. Walsh, T. Rice, P. A. Decker, M. L. Kosel, T. Kollmeyer, H. M. Hansen, S. Zheng, L. S. McCoy, P. M. Bracci, E. Anderson, G. Hsuang, J. L. Wiemels, A. R. Pico, I. Smirnov, A. M. Molinaro, T. Tihan, M. S. Berger, S. M. Chang, M. D. Prados, D. H. Lachance, H. Sicotte, J. E. Eckel-Passow, J. K. Wiencke, R. B. Jenkins, M. R. Wrensch
Journal: Neuro-Oncology (2013)

Genome-wide association studies have implicated single nucleotide polymorphisms (SNPs) in 7 genes as glioma risk factors, including 2 (TERT, RTEL1) involved in telomerase structure/function. We examined associations of these 7 established glioma risk loci with age at diagnosis among patients with glioma. SNP genotype data were available for 2286 Caucasian glioma patients from the University of California, San Francisco (n = 1434) and the Mayo Clinic (n = 852). Regression analyses were performed to test for associations between "number of risk alleles" and "age at diagnosis," adjusted for sex and study site and stratified by tumor grade/histology where appropriate. Four SNPs were significantly associated with age at diagnosis. Carrying a greater number of risk alleles at rs55705857 (CCDC26) and at rs498872 (PHLDB1) was associated with younger age at diagnosis (P = 1.4 × 10−22 and P = 9.5 × 10−7, respectively). These SNPs are stronger risk factors for oligodendroglial tumors, which tend to occur in younger patients, and their association with age at diagnosis varied across tumor subtypes. In contrast, carrying more risk alleles at rs2736100 (TERT) and at rs6010620 (RTEL1) was associated with older age at diagnosis (P = 6.2 × 10−4 and P = 2.5 × 10−4, respectively). These SNPs are risk factors for all glioma grades/histologies, and their association with age at diagnosis was consistent across tumor subgroups. Carrying a greater number of risk alleles might be expected to decrease age at diagnosis. However, glioma susceptibility conferred by variation in telomerase-related genes did not follow this pattern. This supports the hypothesis that telomerase-related mechanisms of telomere maintenance are more associated with gliomas that develop later in life than those utilizing telomerase-independent mechanisms (ie, alternative lengthening of telomeres).
LABORATORY INSPECTION OF VACCINE.
Authors: ADOLPH GEHRMANN
Journal: JAMA (1903)

In this paper the term vaccine is used in the restricted sense, meaning smallpox vaccine. The purchases of vaccine by the Chicago Department of Health have been subject to inspection and test of each lot received since 1894. During July, 1894, an extended investigation of vaccine was made and showed that glycerinated lymph contained fewer bacteria and had a longer period of efficiency than the dry vaccine points. Glycerinated vaccine was therefore introduced and has been used exclusively ever since. The exact date of the first distributions was Aug. 1, 1894. The points herein brought out are consequently based on the inspection of this supply of the glycerinated product. There have been distributed to the vaccinators approximately one million individual vaccinations from that date to this. Some 20,000 tubes have been used for the purpose of testing; 10,000 for the bacteriologic and animal experiments and 10,000 for the clinical
Zidovudine in Patients with HIV Infection
Authors: John P.A. Ioannidis
Journal: Annals of Internal Medicine (1996)

Letters1 February 1996Zidovudine in Patients with HIV InfectionJohn P.A. Ioannidis, MD, Joseph Lau, MD, and Henry S. Sacks, PhD, MDJohn P.A. Ioannidis, MDNew England Medical Center; Boston, MA 02111Mount Sinai Medical Center; New York, NY 10029, Joseph Lau, MDNew England Medical Center; Boston, MA 02111Mount Sinai Medical Center; New York, NY 10029, and Henry S. Sacks, PhD, MDNew England Medical Center; Boston, MA 02111Mount Sinai Medical Center; New York, NY 10029Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-124-3-199602010-00025 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:The risk ratio reported by Bucher and Griffith for progression to AIDS or death in long-term trials is identical to that which we obtained in our paper [1] (0.96 [CI, 0.81 to 1.13]; 0.88 [CI, 0.73 to 1.08]) if deaths not related to HIV infection are excluded. We believe, however, that their subgroup analysis is not sufficiently robust. Despite further stratification according to CD4 count, studies were pooled regardless of the presence or absence of symptoms (an important covariate), and no meta-regression was done. Overall, we claimed no important long-term benefit from early zidovudine treatment for any subgroup ...References1. Ioannidis JP, Cappalleri JC, Lau J, Skolnik PR, Melville B, Chalmers TC, et al. Early or deferred zidovudine therapy in HIV-infected patients with an AIDS-defining illness. A meta-analysis. Ann Intern Med. 1995; 122:856-66. Google Scholar2. Pocock SJ. Clinical Trials. A Practical Approach. New York: J Wiley; 1983. Google Scholar Author, Article, and Disclosure InformationAffiliations: New England Medical Center; Boston, MA 02111Mount Sinai Medical Center; New York, NY 10029 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPredictors and Impact of Patients Lost to Follow-Up in a Long-Term Randomized Trial of Immediate Versus Deferred Antiretroviral Treatment 1 February 1996Volume 124, Issue 3Page: 372-373KeywordsAIDSClinical trialsHIV infectionsRegression analysisRisk managementRisk ratio Issue Published: 1 February 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
TRENDS IN HYPERTENSION PREVALENCE, CONTROL AND GUIDELINES IMPLEMENTATION IN SPAIN THROUGH LAST DECADE.
Authors: Alberto Cordero, Vicente Bertomeu-Martinez, Pilar Mazón, Lorenzo Facila, Juan Cosin, Enrique Galve, Iñaki Lekuona, Moises Rodriguez, Jose Moreno, Jose R. Gonzalez-Juanatey
Journal: Journal of the American College of Cardiology (2011)
Puerperal and Lactational Mastitis in an Industrial Town
Authors: A. A. Fulton
Journal: BMJ (1945)

PRIMARY ATYPICAL PNEUMONIA MEDICALIJOURNAL693outwards from the left upper hilum to the outer subclavicular region.The white cell count was 3,300.There was no sputum throughout the illness.He had eight days' mild pyrexia, and three weeks after the onset radiographs showed only a little residual striation.Case 113.-L/Cpl.H., aged 21, was admitted on Aug. 16 com- plaining of headache, dyspnoea, and general malaise.He also had pain in the right chest anteriorly on respiration.Three days after admission he had a small haemoptysis, but no physical signs were detectable till the following day, when crepitations with distant tubular breathing were heard at the right base and radiographs showed an oval consolidation situated on the diaphragm, which was slightly elevated.The white cell count was 5,650 per c.mm.On admission his temperature was 100°F., but on the two succeeding days it reached 103°F., and settled by lysis on the sixth day.The pulse was never more than 100 and respirations 22. Culture of the sputum showed streptococci, pneumococci, and M. catarrhalis.A radiograph four weeks after the onset showed, only a slight residual opacity.Case 118.-Gdsmn.I., aged 22, was admitted on Sept. 25 with a history of a few hours' headache and shivering.His temperature on admission was 1040 F. and pulse 110.Blood smears were nega- tive for malaria.On the 27th no physical signs were detected, but radiographs showed a fan-shaped area of consolidation in the left upper zone, chiefly peripheral.The left hilar glands were notably
Low Spinal Block in a Case of Eclampsia
Authors: V. H. Cooper, P. V. Lang
Journal: BMJ (1951)

February, 1950, at laparotomy, both tubes were flaccidly distended in their outer third and terminally closed.Case 5.-Aged 34.Mother of three children.One and a half years' sterility.Four years before her attendance at hospital her attempts to procure an abortion resulted in injury to the bladder.She was treated in hospital for seven months on account of sloughing of the bladder.Drainage tubes were inserted in the pelvis.In October, 1948, a salpingogram showed cornual occlusion of the right tube and fimbrial distension of the left tube with questionable FIG.4.-Kymograph obtained in a case in which the radiograph denoted bilateral terminal occlusion.
Heterosexual Transmission of HIV in Haiti
Authors: Marie-Marcelle Deschamps
Journal: Annals of Internal Medicine (1996)

Background: Despite the importance of human immunodeficiency virus (HIV) transmission through heterosexual contact, the incidence of HIV infection in heterosexual cohorts has not been well studied, particularly in the developing world. Objective: To 1) determine the incidence of HIV infection in discordant heterosexual couples [couples in which one partner had HIV infection and the other did not] in Haiti and 2) assess risk factors for and methods of preventing HIV infection. Design: Prospective study. Setting: National Institute for Laboratory Research, Portau-Prince, Haiti. Participants: 475 HIV-infected patients and their noninfected regular sex partners. Measurements: Patients and their partners were evaluated at 3- to 6-month intervals for HIV infection, sexually transmitted diseases, and sexual practices. The efficacy of counseling and provision of free condoms was also evaluated. Results: Among the 177 couples who remained sexually active during the prospective study period, 20 seroconversions to HIV positivity occurred, for an incidence rate of 5.4 per 100 person-years (95% CI, 5.16 to 5.64 per 100 person-years). Thirty-eight couples (21.5%) discontinued sexual activity during the study. Only 1 seroconversion occurred among the 42 sexually active couples (23.7% of the 177 sexually active couples) who always used condoms. In contrast, the incidence in sexually active couples who infrequently used or did not use condoms was 6.8 per 100 person-years (CI, 6.49 to 7.14 per 100 person-years). Transmission of HIV was associated with genital ulcer disease, syphilis, and vaginal or penile discharge in the HIV-negative partner and with syphilis in the HIV-infected partner. Conclusion: Counseling and the provision of free condoms contributed to the institution of safe sex practices or abstinence in 45% of discordant heterosexual couples. However, 55% of couples reported that they continued to have unprotected sex, resulting in an incidence of HIV infection of 6.8 per 100 person-years.
Arteriogenesis, the good and bad of it
Authors: Wolfgang Schaper, Ivo Buschmann
Journal: Cardiovascular Research (1999)

Arteriogenesis, the process of collateral artery growth as an adaptation to major arterial occlusion, can be life- and tissue saving and may alter the natural course of the consequences and organ manifestations of arterial disease. This is achieved by an active growth process that is coupled to complete arterial remodeling with activation of proteases and destruction of the organ tissue in the immediate vicinity of the growing vessel, to create the space for a new artery which expands to about 20 times its original diameter. Much of the growth and remodeling is achieved by attraction, adhesion, activation and invasion of circulating cells, mostly monocytes, but also T-cells and basophiles. Growth factors that are already present, as well as those that are produced by invading cells, produce an environment of inflammation and facilitate coagulation and are therefore pro-atherogenic. It will be a challenge for future therapies with growth factors, chemokines and cytokines to neutralize the atherogenic and to maximize their arteriogenic properties.
Evening the score on sex drugs: feminist movement or marketing masquerade?
Authors: R. Moynihan
Journal: BMJ (2014)

Ahead of this month’s FDA workshop on patient focused drug development for women’s sexual problems, Ray Moynihan questions a campaign to get a rejected drug licensed

A thrice failed antidepressant is at the centre of a new marketing campaign to win approval for what could become the world’s first blockbuster sex pill for women. Frustrated by the drug’s repeated rejection, proponents have orchestrated a fierce attack, accusing the regulator of unfairness, and enlisting support from several well connected women’s organisations in the US. Critics counter that the campaign is exceedingly misleading, that it targets a desire disorder that does not exist, and that approval could see widespread overprescribing of a drug with marginal benefits and real safety concerns.

A few months ago a website called Even the Score emerged, (www.eventhescore.org) attacking the United States Food and Drug Administration with the claim, “Men outscore women 26 to 0 when it comes to FDA approved treatments marketed for Sexual Dysfunction.” The argument is that men have sildenafil and a host of other drugs, but women have none. And according to Even the Score’s website, 43% of women experience sexual dysfunction.

The campaign uses the broad feminist language of rights, choice, and sex equality, but it has a narrow focus as well: it calls on the FDA to act for women “by approving the first-ever drug to treat the most common form of women’s sexual dysfunction.” Without using the drug’s name, it’s a demand for the regulator to approve the thrice failed antidepressant flibanserin, currently being pushed for hypoactive sexual desire disorder— a now obsolescent diagnosis—by new drug company Sprout, a key sponsor of the campaign. Sprout is run by a group of experienced pharmaceutical and investment specialists who reportedly bought flibanserin in 2011 and, according to the business press, have raised tens …
Single cardiac vagal fiber activity, acute myocardial ischemia, and risk for sudden death.
Authors: D Cerati, P J Schwartz
Journal: Circulation Research (1991)

Experimental and clinical evidence indicates that high risk for sudden death is significantly correlated with post-myocardial infarction depression in two "markers" of vagal activity, heart rate variability and baroreflex sensitivity. The present experiments were designed to answer some of the questions generated by those findings. In 33 anesthetized cats, the neural activity of single cardiac vagal efferent fibers was recorded in control conditions and after injection of phenylephrine (n = 33), before and during a 1-hour coronary artery occlusion (CAO) (n = 17), and before and after removal of the left stellate ganglion (n = 16). In the first minute after CAO, vagal activity increased by 35% from 1.66 +/- 0.37 to 2.57 +/- 0.62 impulses/sec (p less than 0.01); despite a slight decline, it remained for the entire CAO above the control values, to which it returned after CAO release. Of 17 cats, ventricular fibrillation occurred in nine (susceptible) and eight survived (resistant). Resistant and susceptible cats had different reflex vagal responses to CAO. Whereas the resistant cats had a 48% (p less than 0.01) increase by the second minute of CAO, susceptible cats had no change (-18%, p = NS) in vagal activity. These differences were independent of blood pressure changes. The increase in vagal efferent activity in response to the blood pressure rise induced by phenylephrine (baroreceptive reflex) was more marked in the resistant cats compared with the susceptible cats (+246 +/- 66% versus +80 +/- 14%, p less than 0.025). Just before the injection of phenylephrine, vagal activity was not different between resistant and susceptible cats (1.58 +/- 0.35 versus 1.48 +/- 0.30 impulses/sec, p = NS). In 16 cats, left stellectomy increased cardiac vagal efferent activity by 75% (p less than 0.01), and the reflex vagal activation secondary to phenylephrine was further enhanced (from 2.2 +/- 0.4 to 4.7 +/- 0.7 impulses/sec, p less than 0.001). These data demonstrate that 1) cardiac vagal efferent activity increases in response to acute myocardial ischemia--much more so among the animals destined to survive, 2) before CAO, susceptible and resistant animals can be identified by the vagal response to blood pressure increase (assessed clinically by baroreflex sensitivity) and not by tonic vagal activity (assessed clinically by heart rate variability), and 3) the findings with left stellectomy support the hypothesis that vagal activity decreases after myocardial infarction because of an increase, secondary to abnormal stretch of the cardiac mechanoreceptors, in cardiac sympathetic afferent traffic, which exerts a tonic restraint on vagal outflow.
Cool with Plaques and Tangles
Authors: Douglas C. Ewbank, Steven E. Arnold
Journal: New England Journal of Medicine (2009)

Survivors to the age of 95 years are a select and hardy few. At current mortality rates, only about 8% of persons will live to the age of 95, and only about half of those will escape dementia. To some extent, they may just be the lucky few. However, there are certainly behavioral, environmental, and hereditary differences that distinguish these older old persons from the rest of us. Many of these differences make these older old persons less vulnerable than younger old persons to a variety of adverse conditions. The biology and experiences of older old persons help us focus . . .
Abstract 3817: Chromosome specific telomeres and breast cancer risk
Authors: Yun-Ling Zheng, Xin Zhou, Christopher A. Loffredo, Peter G. Shields, Bing Sun
Journal: Cancer Research (2011)

Abstract Although telomere dysfunction is a characteristic of breast cancer cells, the relationship between deficiency on individual chromosomal telomeres in normal somatic cells and breast cancer risk has not been characterized. A case-control study was conducted to examine the associations between individual lengths of 92 telomeres in the human genome and the risk of breast cancer in 204 newly diagnosed breast cancer patients and 236 healthy controls. Chromosome arm-specific telomere lengths were measured by telomere quantitative fluorescent in situ hybridization (TQ-FISH). Unconditional logistic regression was used to estimate the risk associations. This genome-wide screen identified that shorter telomere lengths on chromosome Xp and 15p were associated with breast cancer risk in premenopausal women, with adjusted odds ratios (aOR) of 2.5 (95% CI = 1.3, 4.8), and 2.6 (1.3, 5.0), respectively. The study also revealed that greater length differences between homologous telomeres on chromosome 9p, 15p and 15q were associated with breast cancer risk in premenopausal women, with aORs of 4.6 (2.3, 9.2), 3.1 (1.6, 6.0), and 2.8 (1.4, 5.4) respectively. When the subjects were categorized into quartiles, a dose response relationship was observed for all of the above telomeres (P-for-trend &amp;lt; 0.005). This study revealed that telomere deficiencies on chromosome 9p, 15p, 15q and Xp were associated with breast cancer risk in premenopausal women. If confirmed in future studies, chromosomal arm-specific telomeres are likely to be a useful panel of blood-based biomarkers for breast cancer risk assessment, given their strong associations with breast cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3817. doi:10.1158/1538-7445.AM2011-3817
Acute hemolytic transfusion reaction by anti-P1 antibody in pregnancy
Authors: Beenu Thakral, Prasun Bhattacharya, Naveen Agnihotri, R.R. Sharma, Neelam Marwaha, Sarla Gopalan
Journal: American Journal of Hematology (2005)

of thalassemics due to the development of better chelating drugs will surely make HCC a major problem for thalassemics in future.Nowadays the outcome of HCC can be improved by various treatments, and when HCC develops in absence of cirrhosis, liver surgery can be curative [1,2].However, early detection of HCC is mandatory.Our experience suggests that US screening should be performed strictly in thalassemia syndromes, particularly when there is either HCV or HBV infection or sustained iron overload.
Matrix metalloproteinases: not-so-innocent bystanders in heart failure
Authors: Richard T. Lee, Peter Libby
Journal: Journal of Clinical Investigation (2000)

For decades, the classic teaching of the pathophysiology of heart failure has focused, quite reasonably, on the inside of the cardiac myocyte. The dynamic states of the contractile proteins and exquisite controls of intracellular calcium movements coordinate myocardial contraction and relaxation and appeared to be prime suspects in all forms of systolic and diastolic dysfunction. Furthermore, molecular genetics has implicated mutations in the cytoskeleton as important causes of cardiomyopathy in both mice and humans (1). In contrast, the extracellular matrix (ECM) seemed to serve only a passive role, providing a relatively static external structure whose rates of metabolic turnover appeared much too slow to influence cardiac contractility or hypertrophy directly. Cardiac myocytes did their work on the inside, while the matrix seemed to just hang on for the ride.
Tumor necrosis factor mediates experimental pulmonary edema by ICAM-1 and CD18-dependent mechanisms.
Authors: S K Lo, J Everitt, J Gu, A B Malik
Journal: Journal of Clinical Investigation (1992)

(TNF alpha)-induced sequestration of neutrophils (PMN) in lungs and of the resultant PMN-dependent pulmonary edema. Guinea pig lungs perfused with Ringers-albumin were challenged with TNF alpha (1,000 U/ml) for 90 min, followed by addition of fresh perfusate containing 2 x 10(7) human PMN. TNF alpha challenge caused sequestration of PMN in the pulmonary vascular bed as indicated by a threefold increase in lung tissue myeloperoxidase activity (MPO). The activation of the sequestered PMN with phorbol 12-myristate 13-acetate (PMA; 5 x 10(-9) M) produced threefold increases in pulmonary artery (Ppa) and pulmonary capillary hydrostatic (Pcap) pressures, and twofold increases in lung wet-to-dry weight (W/D) ratio and capillary filtration coefficient (Kf,c) over baseline. TNF alpha prestimulation was required for these responses since activation of PMN with PMA in control lungs produced smaller increases in Ppa and Pcap (P less than 0.01) and did not change the W/D and Kf,c. TNF alpha prestimulation also induced the expression of intercellular adhesion molecule (ICAM-1) on pulmonary vascular endothelial cells. Monoclonal antibodies (mAbs) to the neutrophil CD18 integrin (beta-chain of CD11/CD18 complex) (mAb IB4) and to its endothelial cell ligand ICAM-1 (mAb RR1/1) were used to examine the role of PMN adhesion in the TNF alpha-induced responses. Pretreatment of PMN with mAb IB4 prevented PMN uptake and increases in Ppa, Pcap, Kf,c, and W/D ratio. Addition of mAb RR1/1 to the perfusate reduced PMN uptake by 58%, and prevented the increases in Ppa, Pcap, Kf,c, and W/D ratio, as with mAb IB4. The findings indicate that TNF alpha prestimulation of lungs mediates PMN uptake and that this requires the expression of ICAM-1 and its interaction with CD18 integrin on PMN. The activation of PMN sequestered by ICAM-1-dependent mechanism contributes to the development of pulmonary vascular injury and edema.