tbuckley/cabot-search huggingface dataset:
Bretylium Tosylate in Treatment of Severe Hypertension
Authors: K. Somers
Journal: BMJ (1962)

<h3>Background</h3> Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and Trichomonas vaginalis(TV) are among the major causative agents of sexually transmitted infections (STIs). Huge fraction of patients with NG, CT and TV infections are asymptomatic making syndromic case management(SCM) becomes unreliable. Taqman based triplex qPCR assay for simultaneous detection of NG, CT and TV, besides being dependable diagnostic tool, can effectively differentiate between mono-infections and co-infections of these pathogens. <h3>Methods</h3> Endo-cervical dry swabs were procured from non-pregnant females visiting Department of Obstetrics &amp; Gynaecology, VMMC and Safdarjung Hospital, Delhi, India as per ICMR ethical guidelines. DNA was isolated from the samples and presence of the causative agent, if any, was determined using in-house developed Multiplex qPCR assay by employing specific primer-probe sets targeting each pathogen. Analytical sensitivities and specificities were determined for each uniplex assay. In-house developed assay was clinically validated in comparison to published NAAT based assays. <h3>Results</h3> A 108 bp region of orf-1 gene of NG, 133 bp region of pld gene of CT and 147 bp region of pfo-B gene of TV genomic DNA were utilized for identification. Analytical sensitivity of NG uniplex assay was determined to be 10ag of recombinant DNA (3–4 DNA equivalents) and for both CT and TV, it was determined to be 100ag of DNA (30 DNA equivalents). 85 clinical samples have been examined so far and the assay detects NG and CT DNA with 83% and 60% sensitivities, 99% and 100% specificities, 83% and 100% PPV and, 99% and 98% NPV respectively. Two clinical samples among them were co-infected with NG and CT. <h3>Conclusion</h3> In-house developed multiplex qPCR assay provides an opportunity for diagnosis of three highly prevalent and curable STIs in only one assay. The results following validation are motivating enough to project it as a potentially reliable diagnostic tool for their detection.
Development of methods to monitor exposure to 1-nitropyrene.
Authors: K el-Bayoumy, B Johnson, A K Roy, P Upadhyaya, S Partian, S S Hecht
Journal: Environmental Health Perspectives (1994)

On the basis of 32P-postlabeling analysis, treatment of rats with 1-nitropyrene (1-NP) resulted in the formation of multiple DNA adducts in the liver, mammary glands, and peripheral lymphocytes. The one adduct resulting from nitroreduction, N-(deoxyguanosin-8-yl)-1-aminopyrene, constitutes only a minor component among the adducts. In the present study, incubation of calf thymus DNA with mutagenic ring-oxidized metabolites of 1-NP in vitro in the presence and absence of xanthine oxidase also resulted in the formation of multiple adducts. On the basis of their chromatographic behavior, it appears that DNA adducts derived from such metabolites may have been formed in vivo; however, this needs to be confirmed. [3H]1-NP was given to male and female F344 rats and Sprague-Dawley rats by gavage at five dose levels in the range of 0.1 to 1000 micrograms/kg bw. This led to stable hemoglobin adducts accounting for 0.08 +/- 0.05% of the dose (n = 3 rats). The radioactivity associated with hemoglobin following administration of [3H]1-NP was cleared with a half-life of about 14 days, which is faster than that of unmodified erythrocytes in the rat (t1/2 = 30 days). Treatment of the hemoglobin with 1% HCl in acetone, to precipitate the globin, released the radioactivity; it was all bound to the heme moiety. The structures of the heme adducts have not been elucidated; yet, because of their stability, they may be useful as dosimeters for human exposure to 1-NP.(ABSTRACT TRUNCATED AT 250 WORDS)
EXPERIMENTAL SYPHILIS OF ORIENTAL ORIGIN: CLINICAL REACTION IN THE RABBIT
Authors: Louise Pearce
Journal: The Journal of Experimental Medicine (1938)

Two oriental strains of T. pallidum of Chinese origin were compared with two well known occidental strains, the Nichols and the Zinsser-Hopkins, on the basis of the clinical reaction to infection in the rabbit. Four experiments were carried out, two each in Peiping and New York. Animals from American and Chinese sources were represented in each experiment. The results obtained showed that the reaction to both Chinese strains was generally comparable to that of the American strains. But with both Chinese strains, lesions of the eyes were more frequent, the time relations of certain phases of the reaction were shortened, and there was a higher incidence of complete recovery (latency) within the observation period. In view of the well known variability of the syphilitic reaction, however, it was not felt that these qualitative differences in clinical response could be ascribed to inherent or biologically fixed properties of the strains.
Vitamin D Inhibits Monocyte/macrophage Pro-inflammatory Cytokine Production by Targeting Mitogen-Activated Protein Kinase Phosphatase-1
Authors: Y. Zhang, D.Y. Leung, B.N. Richers, Y. Liu, L.K. Remigio, D.W. Riches, E. Goleva
Journal: Journal of Allergy and Clinical Immunology (2012)
Abstract 5317: Non-invasive dynamic bioluminescence imaging of tumor functional vascular changes during antiangiogenic therapy in conscious mice
Authors: Christian R. Schnell, Vanessa Orsini, Stéphanie Barbé, Samuel Arnal, Robert Cozens
Journal: Cancer Research (2011)

Abstract Bioluminescence imaging has been used for several years in oncology research to quantify tumor growth and metastatic spread rather than functional physiological effects. Two recent publications have highlighted the use of non-invasive dynamic bioluminescence imaging (DBLI) in isofluran anesthetized mice to assess vascular changes in subcutaneous xenografts (1) and orthotopic implanted tumors (2) post-treatment. We have previously reported that anesthesia impairs bioluminescence signal intensity (3) and may in turn profoundly affect interpretation of compound activity based on BLI (4). Thus, we decided to investigate DBLI for non-invasive, longitudinal and quantitative monitoring of functional vascular changes (tumor perfusion, blood volume, vascular flow) in conscious mice during antiangiogenic therapy. Subcutaneous xenografts (HCT116 colorectal, U87MG glioblastoma and SJSA-1 osteosarcoma) were treated with a blocking antibody to vascular endothelial growth factor receptor 2 (DC101) and repeatedly examined at bi-weekly intervals. Our results have clearly demonstrated that in all tested models, tumor growth was significantly inhibited (T/C: 0.33, 0.52 and 0.53 for HCT116, U87MG and SJSA-1, respectively) after treatment with DC101 when compared to control. DBLI analysis revealed an initial increase in vascular flow (Day 2 to 3) followed by a gradual decrease after a 2-wk therapy, suggesting early and long-term effects on functional tumor vasculature. Notably, this pattern was more pronounced in highly vascularized (SJSA-1) when compared with less well vascularized (HCT116) tumors. Lastly, very similar decreased microvessel density (MVD) was noted by histological immuno-fluorescence staining following chronic treatment with DC101 in all three tumor models. In conclusion, DBLI measurements in conscious tumor bearing mice offer an optimal and reliable approach for non-invasive functional tumor vessel assessment without the confounding effects of anesthesia. It can be foreseen that with future development of more efficient light-emitting enzyme/substrate systems and the improvement of detection devices it will be possible to increase the sensitivity of this technique allowing the measurement of weaker bioluminescence signals and extending spatial resolution. References: [1] Zhao et al. FASEB J. 22, 2445-2451 (2008). [2] Sun et al. Neurosurgery 66, 751-757 (2010). [3] Schnell et al. AACR meeting (2009), Tumor Biology, Abstract 4006. [4] Schnell et al. EORTC meeting (2010), Animal models, Abstract 261. 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 5317. doi:10.1158/1538-7445.AM2011-5317
Transmission of HIV.
Authors: S. M. Gore
Journal: BMJ (1992)

The European Study Group's findings on Heterosexual Transmission of HIV, is criticized for methodological reasons. A question is raised about how the interaction between the index patient's disease and sex-related efficacy of transmission of HIV is derived. Data need to be made available on the HIV status of the contact at recruitment, the sex of the contact, the number of months of HIV-exposed sexual contact when the index patient had stage 1 disease, the number of months of HIV-exposed sexual contact when the patient had stage 2 disease, and so on. Another question pertains to prospective and past contact for those testing HIV positive and those testing HIV negative who later showed positive results. It is suggested that an improved strategy would be to consider as separate contacts those who where HIV positive at recruitment and those who had seroconversion later. Thus, crude rates of seroconversion can be obtained by a comparison between HIV-exposed sexual contact of female index patients and of male index patients; i.e., 3 seroconversions of females among 135 male contacts, or 2.2/100 HIV- exposed male sexual contacts; and 7 male seroconversions among 313 female contacts, or 2.2/100 HIV-exposed female sexual contacts. The stage of disease is crucial, and monthly exposure rates are pertinent. The data reported were insufficient to address these concerns: 159 male female index patients infected with HIV, of which 16 were HIV positive at recruitment and 3 seroconverted after recruitment; and 404 female contacts of 400 male index patents infected with HIV, of which 75 were seropositive at recruitment and 7 seroconverted subsequently.
Molecular basis of fibrinogen Naples associated with defective thrombin binding and thrombophilia. Homozygous substitution of B beta 68 Ala----Thr.
Authors: J Koopman, F Haverkate, S T Lord, J Grimbergen, P M Mannucci
Journal: Journal of Clinical Investigation (1992)

In an abnormal fibrinogen (fibrinogen Naples) associated with congenital thrombophilia we have identified a single base substitution (G----A) in the B beta chain gene that results in an amino acid substitution of alanine by threonine at position 68 in the B beta chain of fibrinogen. The propositus and two siblings were found to be homozygous for the mutation, whereas the parents and another sibling were found to be heterozygous. Individuals homozygous for the defect had a severe history of both arterial and venous thrombosis; heterozygous individuals had no clinical symptoms. The three homozygotes had a prolonged thrombin clotting time in plasma, whereas the heterozygotes had a normal thrombin clotting time. Fibrinopeptide A and B (FpA and FpB) release from purified fibrinogen by human alpha-thrombin was delayed in both the homozygous propositus and a heterozygous family member. Release of FpA from the normal and abnormal amino-terminal disulfide knot (NDSK) corresponded to that found with the intact fibrinogens, indicating a decreased interaction of thrombin with the NDSK part of fibrinogen Naples. Binding studies showed that fibrin from homozygous abnormal fibrinogen bound less than 10% of active site inhibited alpha-thrombin as compared with normal fibrin, while fibrin formed from heterozygous abnormal fibrinogen bound approximately 50% of alpha-thrombin. These results suggest that the mutation of B beta Ala 68----Thr affects the binding of alpha-thrombin to fibrin, and that defective binding results in a decreased release of FpA and FpB in both homozygous and heterozygous abnormal fibrinogens.
Repeatability of published microarray gene expression analyses
Authors: John P A Ioannidis, David B Allison, Catherine A Ball, Issa Coulibaly, Xiangqin Cui, Aedín C Culhane, Mario Falchi, Cesare Furlanello, Laurence Game, Giuseppe Jurman, Jon Mangion, Tapan Mehta, Michael Nitzberg, Grier P Page, Enrico Petretto, Vera van Noort
Journal: Nature Genetics (2009)
Bladder Neuropathy in Periarteritis Nodosa
Authors: Pierre Amarenco, Gérard Amarenco, Marielle Baudrimont, Etienne Roullet, René Marteau
Journal: Annals of Internal Medicine (1989)

Letters and Corrections1 March 1989Bladder Neuropathy in Periarteritis NodosaPierre Amarenco, MD, Gérard Amarenco, MD, Marielle Baudrimont, MD, Etienne Roullet, MD, René Marteau, MDPierre Amarenco, MDSearch for more papers by this author, Gérard Amarenco, MDSearch for more papers by this author, Marielle Baudrimont, MDSearch for more papers by this author, Etienne Roullet, MDSearch for more papers by this author, René Marteau, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-110-5-411 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: Neuromuscular complications of periarteritis nodosa have been well described (1); however, the occurrence of bladder paralysis has not been reported.A 74-year-old woman was hospitalized in February 1987 for a gait disturbance and generalized weakness. Since September 1986, she had noted the absence of voiding sensation and used to urinate once daily when she thought her bladder was full. Later, voiding became long and difficult but remained painless, and she used abdominal pressure. Her symptoms progressively worsened until a severe motor deficit from mononeuritis multiplex prompted her hospitalization. Perineal examination showed the loss of all conus reflexes...References1. MooreFauci PA. Neurologic manifestations of systemic vasculitis: a retrospective and prospective study of the clinicopathologic features and responses to therapy in 25 patients. Am J Med. 1981;71:517-24. CrossrefMedlineGoogle Scholar2. HaldBradley TW. The Urinary Bladder: Neurology and Dynamics. Baltimore: William and Wilkins; 1982. Google Scholar3. BuckReedSiddiq APY. Bladder dysfunction and neuropathy in diabetes. Diabetology. 1976;12:251-8. CrossrefMedlineGoogle Scholar4. AmarencoDobrinskyLacroixPerrigot GCPM. Les troubles vésico-sphinctériens et sexuels des éthyliques: etude de 170 cas. In: Entretiens de Rééducations. Paris: Masson; 1987:102-8. Google Scholar5. AmarencoCohenAmarencoRoulletMarteau PPGER. Une cause rare d'incontinence urinaire curable: l'artérite giganto-cellulaire. Presse Méd. 1987;16:1058. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited BySingle-Organ Genitourinary VasculitisA 53-Year-Old Man With Dysuria, Pyuria, and Genital UlcersHemorrhagic cystitis complicating untreated necrotizing vasculitisBladder Neuropathy and Gastric Paralysis in Polyarteritis Nodosa Associated with Hepatitis B Virus 1 March 1989Volume 110, Issue 5Page: 411-412KeywordsBladderHospitalizationsMononeuritisNeuropathyParalysisReflexesUrination Issue Published: 1 March 1989 PDF DownloadLoading ...
Deprivation, disease, and death in Scotland: graphical display of survival of a cohort
Authors: J. Chalmers, S. Capewell
Journal: BMJ (2001)

Death rates are widely used as a convenient way of summarising important aspects of health in a population.However, they are not always easy to interpret, and even when techniques such as standardisation are used the impact of premature death may be difficult to assess.Cohort analysis provides summary information that takes account of age at death and that can be displayed graphically in a readily understood format.First used in 1870 by the statistician William Farr, this straightforward technique deserves wider use. 1 It is widely accepted that deprivation increases the risk of early death.However, the age at which death from specific causes occurs and the relative contributions of these causes to mortality are rarely described clearly. 2 We used data on survival in a cohort of middle aged people, divided into groups according to deprivation, to examine the relation between age, deprivation, and causes of death in a straightforward and graphical way.
Abstract IA02: A drug repositioning approach identifies tricyclic antidepressants as inhibitors of small cell lung cancer.
Authors: Nadine Jahchan, Dudley Joel, Pawel Mazur, Joel Neal, Purvesh Khatri, Atul Butte, Julien Sage
Journal: Clinical Cancer Research (2014)

Abstract Small cell lung carcinoma (SCLC) is highly aggressive and metastatic neuroendocrine lung cancer with a dismal 5-year survival. While a majority of patients is initially responsive to chemotherapy, chemoresistant tumors rapidly recur. There are no approved targeted therapies for SCLC. We used a systematic drug-repurposing computational approach querying a large number of gene expression datasets to identify new candidate FDA-approved drugs that may be used to treat SCLC. This analysis identified tricyclic antidepressants (TCAs) and related molecules as possible inhibitors of SCLC. Indeed, these compounds potently induce apoptotic cell death in chemonaïve and chemoresistant tumor cells in culture, in a genetically engineered mouse model, and in human SCLC tumor cells transplanted into immunocompromised mice. Imipramine and Promethazine, the two top candidate drugs, activate stress pathways and induce apoptosis and necrosis in SCLC cells, in part by blocking autocrine survival signals involving neurotransmitters and their receptors (GPCRs). The candidate drugs inhibit the expansion of other neuroendocrine tumors, including pancreatic neuroendocrine tumors. These experiments underscore the power of bioinformatics-based drug-repositioning approaches to rapidly repurpose FDA-approved drugs and identify a novel class of candidate molecules to treat patients with SCLC. In addition, our experiments highlight the importance of autocrine mechanisms promoting the growth of neuroendocrine tumor cells. Citation Format: Nadine Jahchan, Dudley Joel, Pawel Mazur, Joel Neal, Purvesh Khatri, Atul Butte, Julien Sage. A drug repositioning approach identifies tricyclic antidepressants as inhibitors of small cell lung cancer. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr IA02.
ASYMPTOMATIC FIREFIGHTERS WITH METABOLIC SYNDROME HAVE A HIGH INCIDENCE OF BOTH CORONARY AND CAROTID PREMATURE ATHEROSCLEROSIS-ASSOCIATED WITH INCREASED THROMBOTIC AND INFLAMMATORY MARKERS
Authors: Lakshmana K. Pendyala, CATHERINE SKRIFVARS, BRENDA GARRETT, RADHIKA R. GADESAM, KATHRYN MOMARY, H ROBERT SUPERKO
Journal: Journal of the American College of Cardiology (2010)
Why have prison needle exchange programmes not yet been rolled out in the UK?
Authors: J. Brett
Journal: BMJ (2012)

Consumer wearable and smartphone devices provide an accessible means to objectively measure physical activity (PA) through step counts. With the increasing proliferation of this technology, consumers, practitioners and researchers are interested in leveraging these devices as a means to track and facilitate PA behavioural change. However, while the acceptance of these devices is increasing, the validity of many consumer devices have not been rigorously and transparently evaluated. The Towards Intelligent Health and Well-Being Network of Physical Activity Assessment (INTERLIVE) is a joint European initiative of six universities and one industrial partner. The consortium was founded in 2019 and strives to develop best-practice recommendations for evaluating the validity of consumer wearables and smartphones. This expert statement presents a best-practice consumer wearable and smartphone step counter validation protocol. A two-step process was used to aggregate data and form a scientific foundation for the development of an optimal and feasible validation protocol: (1) a systematic literature review and (2) additional searches of the wider literature pertaining to factors that may introduce bias during the validation of these devices. The systematic literature review process identified 2897 potential articles, with 85 articles deemed eligible for the final dataset. From the synthesised data, we identified a set of six key domains to be considered during design and reporting of validation studies: target population, criterion measure, index measure, validation conditions, data processing and statistical analysis. Based on these six domains, a set of key variables of interest were identified and a ‘basic’ and ‘advanced’ multistage protocol for the validation of consumer wearable and smartphone step counters was developed. The INTERLIVE consortium recommends that the proposed protocol is used when considering the validation of any consumer wearable or smartphone step counter. Checklists have been provided to guide validation protocol development and reporting. The network also provide guidance for future research activities, highlighting the imminent need for the development of feasible alternative ‘gold-standard’ criterion measures for free-living validation. Adherence to these validation and reporting standards will help ensure methodological and reporting consistency, facilitating comparison between consumer devices. Ultimately, this will ensure that as these devices are integrated into standard medical care, consumers, practitioners, industry and researchers can use this technology safely and to its full potential.
Oh Wretched We...
Authors: Norman S. Blackman
Journal: JAMA (1965)

To the Editor:—  It was interesting to note the parry and riposte ( JAMA  193 :274 [July 26] 1965), concerning the use of the personal pronoun I in editorial comments.  Although editorials are often based on observed facts, they usually contain much voicing of the editor's personal opinion. Such comment implies an invitation to readers who have observed other facts, and therefore have other opinions, to demur.  A reader's dissenting opinion may be construed, as appears in this case, to suggest a personal attack upon the editor. This is often neither desired nor intended but is unavoidable when the personal pronoun is used without suitable restraint.  It would seem, therefore, that, in the interest of good taste and to avoid personal unpleasantries, the use of the personal pronoun I should be kept to an absolute minimum in editorial comments.
Migration and Health: Discovering New Territory for Bioethics
Authors: Verina Wild
Journal: The American Journal of Bioethics (2012)

Click to increase image sizeClick to decrease image size Acknowledgments I thank members of the Institute of Biomedical Ethics, Zurich (Nikola Biller-Andorno, Carina Fourie, Jan-Christoph Heilinger, Daniel Strech, Annette Rid), Samia Hurst and Madison Powers for their valuable feedback on this commentary. Very special thanks to Ron Bayer, with whom I had the pleasure of discussing my thoughts thoroughly.1. If not specified further, the term "migrant" includes all groups of migrants (e.g., migrant workers, refugees, asylum seekers, undocumented migrants).
Aberrant Carotid Artery Injured at Myringotomy
Authors: James J. Reilly
Journal: JAMA (1983)

THE NORMAL internal carotid artery enters the base of the skull through the carotid canal. The artery then bends medially and anteriorly, traversing the petrous bone and cavernous sinus, before emerging medial to the anterior clinoid process. As it passes through the bony petrous ridge, the artery is separated from the middle ear cavity by the tympanic plate. This 0.5-mm-thick plate may be disrupted in basilar skull fractures, displacing the carotid artery into the middle ear. The artery may also pass through the middle ear because of congenital anomalies in its course. Such a vessel may be seen through the tympanic membrane, where it may be mistaken for hemorrhage behind the drum or a tumor. The vessel may be injured during myringotomy; attempts to perform a biopsy of the "mass" may be disastrous. We recently treated a child who experienced massive hemorrhage from his ear after biopsy of such a