tbuckley/cabot-search huggingface dataset:
Natural variability of lung function in young healthy school children
Authors: Jane Kirkby, Vassiliki Bountziouka, Sooky Lum, Angie Wade, Janet Stocks
Journal: European Respiratory Journal (2016)

Knowledge about long-term variability of lung function in healthy children is essential when monitoring and treating those with respiratory disease over time. The aim of this study was to define the natural variability in spirometry in young children after an interval of 12 months. The Size and Lung function In Children study was a prospective study designed to assess spirometry and body size, shape and composition in a multi-ethnic population of London school children. 14 schools with a wide range of socioeconomic circumstances were recruited. Spirometric and anthropometric assessments and parental questionnaires pertaining to respiratory symptoms, previous medical history, pubertal status and socioeconomic circumstances were completed at baseline and ∼1 year later. Technically acceptable spirometry data on two occasions ∼1 year apart (range 9–16 months) were available in 758 children (39% boys, mean± sd age 8.1±1.6 years), 593 of whom were classified as “healthy”. Mean± sd within-subject between-test variability was 0.05±0.6 z-scores, with 95% of all the children achieving a between-test variability within ±1.2 z-scores (equating to ∼13% predicted). Natural variations of up to 1.2 z-scores occur in healthy children over ∼1 year. These must be considered when interpreting results from annual reviews in those with lung disease who are otherwise stable, if unnecessary further investigations or changes in treatment are to be avoided.
FDA’s Foray Into Big Data Still Maturing
Authors: Bridget M. Kuehn
Journal: JAMA (2016)

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The Heart in Hypertension
Authors: Edward D. Frohlich, Carl Apstein, Aram V. Chobanian, Richard B. Devereux, Harriet P. Dustan, Victor Dzau, Fetnat Fauad-Tarazi, Michael J. Horan, Melvin Marcus, Barry Massie, Marc A. Pfeffer, Richard N. Re, Edward J. Roccella, Daniel Savage, Clarence Shub
Journal: New England Journal of Medicine (1992)

HYPERTENSIVE heart disease can be defined as the response of the heart to the afterload imposed on the left ventricle by the progressively increasing arterial pressure and total peripheral resistance produced by hypertensive vascular disease. Although the response sometimes appears to be out of proportion to the level of the arterial pressure, it is primarily the result of the hemodynamic overload. Hypertension can cause or is related to various cardiac manifestations, among them left ventricular hypertrophy, congestive heart failure, cardiac dysrhythmias, and ischemic heart disease. Although the risk of atherosclerotic coronary heart disease is related to the systolic and diastolic . . .
Gene expression profiling for prediction of distant metastasis and survival in primary nasopharyngeal carcinoma
Authors: K. J. Kao, S. H. Cheng, A. T. Huang
Journal: Journal of Clinical Oncology (2006)

5503 Background: Distant metastasis is the major cause of treatment failure for nasopharyngeal carcinoma (NPC). An accurate means to predict potential of distant metastasis before therapy could allow optimization and further improvement of treatment. Gene expression profiling was performed to identify such predictors. Methods: mRNA transcript profiling was performed using Affymetrix U133A GeneChips on 138 biopsy specimens of primary NPC obtained before therapy and stored in liquid nitrogen. The specimens represented two groups of patients: distant metastasis &lt;3 years after initial therapy (high risk group, n = 47) vs no distant metastasis after &gt;3 years of follow-up (low risk group, n = 91). Two thirds of cases in each risk group were randomized to a training set and 1/3 to an independent test set. Supervised analyses were conducted to discover gene expression signatures associated with metastasis in the training set (n = 96). Genes were selected by Kruskal-Wallis test, grouped by self-organizing-map and further selected by logistic regression. Predictive models were established using logistic regression and k-nearest neighbors (kNN). The predictors thus discovered were validated using independent test set (n = 42). Results: Two molecular predictors were established for identification of patients with high or low risk of developing distant metastasis. The first predictor was based on 52 genes and kNN. The second predictor was based on 12 genes and logistic regression. The specificity, the sensitivity and the accuracy determined on the independent test set were 86%, 69% and 81% for the 52-genes predictor, and 72%, 85% and 77% for the 12-genes predictor. The accuracy increased to 85% and the estimated hazard ratio between predicted high and low risk was 11.1 (95% CI=2.4 to 52.4, p = 0.002), when both molecular predictors were used in combination. Log rank test showed significant difference in overall survival between patients predicted with low and high risk for distant metastasis in the test set (p = 0.003). Conclusions: mRNA transcript profiling of primary tumors of NPC can be used to determine the risk of distant metastasis. The method can be used to identify NPC patients at high metastatic risk to undergo trials of new modalities of treatment at the time of diagnosis. No significant financial relationships to disclose.
SAT0159 Long-Term Follow-Up of Children Born to Mothers with Chronic Arthritides and Exposed in Utero to Anti-TNF-Alpha Agents: A Case-Control Study
Authors: M. Agosti, L. Andreoli, C. Bazzani, C. Nalli, R. Reggia, R. Gorla, M. Taglietti, A. Lojacono, M. Motta, A. Tincani
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Anti-TNFalfa agents have been used to control disease activity of patients with Chronic Arthritides (Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosis Spondilitis) during the wash-out period of teratogenic drugs. Patients with flares during pregnancy may also receive anti-TNFalfa agents during the 2nd-3rd trimester. <h3>Objectives</h3> To investigate the health and developmental conditions of children who were exposed <i>in utero</i> to anti-TNFalfa agents and to compare them with non-exposed children born to women with the same disease. <h3>Methods</h3> An <i>ad-hoc</i> created questionnaire was submitted to women who were followed during pregnancy by a multidisciplinary team (rheumatologist, gynaecologist, neonatologist). Data on birth, lactation, weaning, growth parameters, developmental milestones, vaccinations and disease conditions were collected for the first 24 months of life. <h3>Results</h3> The characteristics of 24 cases (9 male, 15 female) (20 exposed to etanercept, 3 to adalimumab, 1 to certolizumab) and 24 controls (12 M, 12 F) are reported in the table (median value, interquartile range). Eighteen children were exposed during the first trimester (discontinuation of anti-TNFalfa agent at positive pregnancy index), while six during the 2nd-3rd trimester (discontinuation at 34th-37th week). Both cases and controls underwent vaccinations without any severe complications. Vaccinations were protective. Only one child developed chicken-pox despite vaccination (exposure to etanercept in the 1st trimester, until the positive pregnancy index). <h3>Conclusions</h3> No differences in birth parameters, congenital malformations, and developmental steps in the first 24 months of life were found between cases and controls. Growth parameters were within the curves of the general population. Cases received more vaccinations than controls. This may be due to the feeling by either parents or paediatricians that these children exposed to immunosuppressive agents could be more susceptible to infectious diseases. No relevant infectious diseases nor post-vaccine complications were noted in the 6 children exposed to anti-TNFalfa during the 2nd-3rd trimester of gestation. Neurodevelopmental problems were recorded in 2 children: an autism spectrum disorder in one male exposed to etanercept in the 2nd-3rd trimester and a language delay in a male control. Globally, the long-term follow-up of children supports the safety of use of anti-TNFalfa agents, either preconceptionally or during the 2nd-3rd trimester of pregnancy. <h3>References</h3> Ostensen, M. (2014) Safety issues of biologics in pregnant patients with rheumatic diseases, Academy of Sciences, New York. <h3>Disclosure of Interest</h3> None declared
Clinical Studies on the Activity of Orally Administered Cortisone
Authors: George W. Thorn, Albert E. Renold, D. Laurence Wilson, Thomas F. Frawley, Dalton Jenkins, Jose Garcia–Reyes, Peter H. Forsham
Journal: New England Journal of Medicine (1951)

AS EARLY as the end of the last century there were indications in the literature that adrenal cortical hormones were effective when given orally. Notable among these was a report by Osler in 1896 of a patient with Addison's disease who appeared to respond clinically to a glycerol extract of hog adrenal glands.1 In 1931 Britton and Silvette2 , 3 demonstrated conclusively that an orally administered adrenal extract could provide adequate substitution therapy in adrenalectomized cats. It was logical, then, that cortisone, once available in quantity, should be tried by a route that offers so many clinical advantages.The clinical effectiveness of . . .
Clinical and Genetic Abnormalities in Patients with Friedreich's Ataxia
Authors: Alexandra Dürr, Mireille Cossee, Yves Agid, Victoria Campuzano, Claude Mignard, Christiane Penet, Jean-Louis Mandel, Alexis Brice, Michel Koenig
Journal: New England Journal of Medicine (1996)

Friedreich's ataxia, the most common inherited ataxia, is associated with a mutation that consists of an unstable expansion of GAA repeats in the first intron of the frataxin gene on chromosome 9, which encodes a protein of unknown function.
Clinical Hyperbaric Oxygenation with Severe Oxygen Toxicity
Authors: Robert L. Fuson, Herbert A. Saltzman, Wirt W. Smith, Robert E. Whalen, Suydam Osterhout, Roy T. Parker
Journal: New England Journal of Medicine (1965)

HYPERBARIC oxygenation has recently been used in the successful treatment of severe anaerobic infections.1 2 3 Because of these favorable reported results, we gave a patient with an overwhelming anaerobic infection hyperbaric oxygenation in addition to standard forms of therapy. Initially, she improved during treatment and appeared to tolerate easily the high oxygen tensions and increased atmospheric pressures. With further hyperoxygenation treatments, however, convulsions and breathlessness occurred. Ultimately, she died while manifesting severe respiratory insufficiency, and marked pulmonary oxygen toxicity was confirmed at autopsy. Because these serious hazards of therapeutic hyperbaric oxygenation are not fully appreciated, this case report has been prepared. . . .
National practice of radiation therapy and chemoradiation therapy for esophageal cancer in Japan; Results of Patterns of Care Study (1999–2001)
Authors: M. Kenjo, T. Uno, M. Oguchi, K. Gomi, T. Yamashita, D. Yamahana, T. Teshima
Journal: Journal of Clinical Oncology (2005)

4193 Background: Patterns of Care Study (PCS) was conducted to reveal the current status of radiation therapy (RT) and chemoradiation therapy (CRT) for esophageal cancer in Japan. Methods: PCS data format for esophageal cancer was imported to Japan from the United States courtesy of the American College of Radiology. A national survey of 76 facilities including both academic and nonacademic institutions was conducted using the original two-stage cluster random sampling. Eligible criteria were as follows; start radiation therapy (RT) between 1999 and 2001, no evidence of distant organic metastasis (M1b), squamous cell, adenosquamous cell, or adenocarcinoma histology, Karnofsky performance status 60–100, tumors in the thoracic esophagus, and no prior malignancies within the last 5 years. Detailed information was accumulated on 621 patients. Patients were classified according to 1997 UICC criteria. Results: Median age of patients was 68 years. 87% were male and 13% were female. 99% had squamous cell histology. 54% had main lesion in middle thoracic esophagus and 3% had in beneath diaphragm. 13% had stage I disease, 32% had stage IIA or IIB, 43% had stage III and 10% had stage IV disease. All patients received RT. 63% received chemotherapy and 32% received esophagectomy. Patients aged 75 years or more were more frequently treated by RT alone (55%) than by CRT (36%). Preoperative CRT was used for 17% and definitive CRT was used for 39%. Median total dose of RT was 60Gy for all patients, 40Gy for preoperative CRT group and 60Gy in definitive CRT group. 49% of the CRT group received more than 60Gy of external RT. Among CRT group, 88% received chemotherapy concurrently. Cisplatin was used for 85% of CRT group and 5FU was for 98%. Administration schedule of concurrent chemotherapy was daily for 67% of the CRT patients, weekly for 9% and tri-weekly or monthly for 12%. 2% of the patients were treated on approved investigational protocols. Conclusions: CRT has become common for esophageal cancer but used not frequently for elderly patients. High total RT dose was used for CRT patients. Cisplatin and 5FU are the main agents for concurrent CRT. Daily administration schedule was widely used in Japan. No significant financial relationships to disclose.
Infection with Hepatitis GB Virus C in Patients on Maintenance Hemodialysis
Authors: Kazuo Masuko, Takehiro Mitsui, Keiko Iwano, Chikao Yamazaki, Kenji Okuda, Teruo Meguro, Naoki Murayama, Taisuke Inoue, Fumio Tsuda, Hiroaki Okamoto, Yuzo Miyakawa, Makoto Mayumi
Journal: New England Journal of Medicine (1996)

A recently discovered non-A–E hepatitis virus has been designated hepatitis GB virus C (HGBV-C), but little is known about its mode of transmission and its clinical manifestations. We studied 519 patients on maintenance hemodialysis to determine whether they were infected with HGBV-C.
PWE-102 Urinary 1h nuclear magnetic resonance spectroscopy profiling in hepatoecellular carninoma in a bangladeshi cohort corroborates a urinary metabolic fingerprint for liver cancer
Authors: IJ Cox, C Podrini, LJ Markwick, R Williams, M Al-Mahtab, F Akbar, S Rahman, A Islam, S Montagnese, M Crossey, M McPhail, SD Taylor-Robinson
Journal: Gut (2015)

<h3>Introduction</h3> Urinary metabolic profiling using nuclear magnetic resonance (NMR) spectroscopy has an increasing role in both understanding the pathophysiology of cirrhosis, the development of hepatocellular cancer (HCC) and the discrimination of malignant and non-malignant hepatic nodules arising on the background of cirrhosis. Clinical cohorts from Egypt,<sup>1</sup>Nigeria<sup>2,3</sup>and The Gambia<sup>2</sup>have been studied and consensus is emerging for an identifying urinary fingerprint of HCC. The aim of this study was to establish if a similar urinary NMR fingerprint for HCC could be identified in a Bangladeshi cohort. <h3>Method</h3> Urine samples were collected with local research ethics approval and informed consent from 21 Bangladeshi patients with HCC diagnosed by ultrasound and standard clinical tests. Proton (<sup>1</sup>H) NMR spectra were acquired using a JEOL ECP 500 11.7 Tesla spectrometer with a pulse-collect sequence and pre-saturation of the water signal. The HCC urinary <sup>1</sup>H NMR spectral profiles were compared to 18 archived urinary <sup>1</sup>H NMR spectral profiles from Western European healthy subjects. Processed <sup>1</sup>H-NMR spectroscopy data underwent further analysis with principal component analysis (PCA). <h3>Results</h3> PCA illustrated that the urinary <sup>1</sup>H NMR spectral profiles from HCC subjects differed to the control cohort across range of metabolites, including reduced hippurate and creatinine levels but increased creatine levels. These findings are consistent with the published findings from the studies of various African populations.<sup>1,2,3</sup> <h3>Conclusion</h3> Urinary metabolite changes continue to be identified in subjects with HCC, which may be consistent with the diverse effects of HCC on both human physiology and gut bacterial action. Our studies further support the observation of candidate urinary biomarkers of HCC which may aid the development of a simple urinary screening test. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Shariff MI, <i>et al</i>. Urinary metabolic biomarkers of hepatocellular carcinoma in an Egyptian population: a validation study. J Proteome Res. 2011;10:1828–1836 Ladep NG, <i>et al</i>. Discovery and validation of urinary metabotypes for the diagnosis of hepatocellular carcinoma in West Africans. Hepatology 2014;60:1291–1301 Shariff MI, <i>et al</i>. Characterization of urinary biomarkers of hepatocellular carcinoma using magnetic resonance spectroscopy in a Nigerian population. J Proteome Res. 2010;9:1096–1103
IMPS-28PD-L1 EXPRESSION AND PROGNOSTIC IMPACT IN GLIOBLASTOMA
Authors: Edjah K. Nduom, Jun Wei, Nasser Yaghi, Neal Huang, Ling-Yuan Kong, Konrad Gabrusiewicz, Xiaoyang Ling, Shouhao Zhou, Cristina Ivan, Jie Qing Chen, Jared Burks, Greg Fuller, George Calin, Charles Conrad, Caitlin Creasy, Krit Ritthipichai, Laszlo Radvanyi, Amy Heimberger
Journal: Neuro-Oncology (2015)

BACKGROUND: Therapeutic targeting of the immune checkpoints CTLA-4 and PD-1/PD-L1 have demonstrated tumor regression in clinical trials, and phase II trials are ongoing in glioblastoma. Previous reports have suggested that responses are more frequent in patients with tumors expressing PD-L1; however, this has been disputed. At issue is the validation of PD-L1 biomarker assays and prognostic impact. METHODS: Using immunohistochemical analysis, we measured the incidence of PD-L1 expression in 94 patients with glioblastomas. We determined the total number of PD-L1-expressing cells within the glioblastomas and validated this finding using ex vivo glioblastoma flow cytometry, with further analysis of T cell populations. We evaluated the association between PD-L1 expression and median survival time using the protein expression data sets and mRNA from The Cancer Genome Atlas (TCGA). RESULTS: The median percentage of PD-L1-expressing cells in glioblastoma by cell surface staining is 2.77% (range 0-86.6%, n = 92), similar to the percentage found by ex vivo flow cytometry. The majority of glioblastoma patients (61%) had tumors with at least 1% PD-L1-positive cells, and 38% had at least 5% PD-L1 expression. PD-L1 and PD-1 are commonly expressed on glioblastoma-infiltrating T cells. Expression of PD-L1 is prognostic by multivariate analysis for a negative glioblastoma outcome by both immunohistochemistry (p = 0.018) and mRNA expression analysis of TCGA data (p = 0.009). Expression of PD-1 mRNA is correlated with perforin 1 (P 0.0001), both markers of cytolytic activity, as well as the T cell markers CD3 (P < 0.0001), CD4 (P < 0.0001) and CD8 (P < 0.0001). PD-L1 mRNA expression is correlated with granzyme A (P < 0.0001), CD3 (P = 0.0099) and CD4 (P < 0.001). CONCLUSIONS: The incidence of PD-L1 expression in glioblastoma patients is frequent but is confined to a minority subpopulation-similar to other malignancies that have been profiled for PD-L1 expression. Higher expression of PD-L1 is correlated with worse outcome.
Jaundice during Chlorpromazine Therapy
Authors: Jacob Zatuchni, Gladys Miller
Journal: New England Journal of Medicine (1954)

CHLORPROMAZINE hydrochloride, 10-(3-di-methylaminopropyl)-2-chlorphenothiazine hydrochloride, is being used, apparently with remarkable benefit, in the treatment of various neuropsychiatric disorders and as an antiemetic, analgesic and sedative.1 2 3 The following case is reported because of the occurrence of jaundice for which no cause besides chlorpromazine was found.Case ReportJ.M., a 70-year-old woman, was admitted to the hospital on May 24, 1954, because of jaundice. For 3 years she had had many episodes of mental depression, for which electroshock therapy had been given on several occasions. Because the depressed state persisted she had entered a private mental institution, where, on April 28, administration . . .
Letrozole (Femara) causes potent suppression of breast cancer tissue estrogen levels in the neoadjuvant setting
Authors: J. Geisler, H. Helle, D. Ekse, N. K. Duong, D. Evans, P. E. Lønning
Journal: Journal of Clinical Oncology (2006)

10532 Background: Aromatase inhibitors of the third generation like letrozole, anastrozole and exemestane are known to suppress plasma estrogens by 90–99% in postmenopausal women. However, little is known about their influence on tissue estrogen levels. Methods: We investigated the effect of neoadjuvant treatment with letrozole (2.5 mg o.d.) given for 16 weeks to patients with locally advanced breast cancers on tissue levels of estradiol (E 2 ), estrone (E 1 ) and estrone sulfate (E 1 S) measured with a previously published, highly sensitive, HPLC-RIA method (J. Steroid. Biochem. Mol. Biol. 72, 259–264, 2000). All patients had either estrogen receptor (ER) and/or progesterone receptor (PGR) positive tumors (at least one of the receptors expressed in &gt; 50% of the tumor cells). Results: Mean tissue levels of E 2 , E 1 and E 1 S were found to be 475.8, 272.4, and 160.5 fmol/g tissue at baseline (geometric mean values). Following 16 weeks of treatment with letrozole, these levels fell to 11.3, 18.2, and 16.0 fmol/g corresponding to a suppression of tissue levels of E 2 , E 1 and E 1 S by 97.6%, 90.7%, and 90.1%, respectively. All plasma levels of E 2 , E 1 and E 1 S were in the normal range expected for postmenopausal women prior to treatment with letrozole. The individual plasma estrogen fractions were found suppressed by 96.6%, 99.1% and 99.5%, respectively, during treatment with letrozole. Conclusions: Treatment with neoadjuvant letrozole 2.5 mg o.d. potently suppressed tissue estrogen levels in postmenopausal breast cancer patients by 90.1 to 97.6%, surpassing the results previously reported for anastrozole in a similar setting (Clin. Cancer Res. 7, 1230–1236, 2001). While a significant superiority of letrozole versus anastrozole concerning total body aromatase inhibition and plasma estrogen suppression has previously been recorded (J. Clin. Oncol. 20 (3), 751–757, 2002), we are now able to extend this observation to tissue estrogen levels as well. Letrozole (2.5 mg o.d.) seems superior to anastrozole 1 mg daily with respect to plasma as well as tissue estrogen suppression, advocating head to head comparison of these compounds in early breast cancer. [Table: see text]