tbuckley/cabot-search huggingface dataset:
Heterozygosity for E292V in ABCA3, lung function and COPD in 64,000 individuals
Authors: Marie Bækvad-Hansen, Børge Nordestgaard, Morten Dahl
Journal: European Respiratory Journal (2012)

Recessive mutations in the  ATP-binding-cassette-member A3  ( ABCA3 ) gene are associated with chronic lung disease in childhood, but frequency of chronic lung disease due to  ABCA3  mutations in the general population is unknown. We tested the hypothesis that individuals heterozygous for  ABCA3  mutations have reduced lung function and increased risk of COPD in the general population.  We resequenced 760 individuals and identified three novel (H86Y, A320T, A1086D) and four previously described mutations (E292V, P766S, S1262G, R1474W) in  ABCA3 . We genotyped the entire Copenhagen City Heart study (n=10,604) to assess the clinical importance of these mutations. To validate our findings we genotyped an additional 54,395 individuals from the Copenhagen General Population Study for the E292V mutation.  In the Copenhagen City Heart Study E292V heterozygotes had 5% reduced FEV 1 % predicted (t-test: p=0.008) and 3% reduced FVC % predicted compared with noncarriers (p=0.04) and an increased odds ratio for COPD of 1.9 (95% CI: 1.1-3.1). In contrast, the A1086D mutation was associated with increased FEV 1 % predicted (p=0.03) and FVC % predicted (p=0.008) in the Copenhagen City Heart Study. None of the other  ABCA3  mutations associated with lung function or COPD risk. In the larger Copenhagen General Population Study, and in the two studies combined, E292V heterozygotes did not have reduced lung function or increased risk of COPD (p≥0.11), while this was the case for the positive controls,  surfactant protein-B  121ins2 heterozygotes and  α 1 -antitrypsin  ZZ homozygotes.  Our results indicate that partially reduced ABCA3 activity due to E292V is not a major risk factor for reduced lung function and COPD in the general population.
Cytologic Manifestations of Neoplastic Transformation &lt;italic&gt;In Vitro&lt;/italic&gt;
Authors: Barbara E. Barker, Katherine K. Sanford
Journal: JNCI Journal of the National Cancer Institute (1970)

Our objective was to test whether cytologic diagnoses of neoplastic transformation could be made accurately on cultured cells in vitro. Cytologic criteria of malignancy as applied to tissues or exfoliated cells in vivo served as guidelines for the diagnoses in vitro. Diagnosis was made on stained coverslip preparations sent coded from Bethesda to Providence. Neoplastic state was determined at Bethesda by implantation of samples of the tissue culture cells in compatible hosts for assay of their capacity to grow progressively as invasive, serially transplantable neoplasms. Several populations of mixed cell types from embryos of the mouse, hamster, and rat were followed during long-term culture. Of the 12 cell lines initiated, all but one underwent neoplastic transformation. Most lines undergoing such transformation showed a progression of cytologic changes in the following order: increase in cytoplasmic basophilia, increase in number and size of nucleoli, increase in nuclear:cytoplasmic ratio, retraction of cytoplasm, and formation of clusters and cords of cells. Although a few cultures that tested as non-neoplastic or borderline showed certain of the early changes in some cells, all cultures showing the first 4 or 5 changes gave rise to sarcomas in vivo. Diagnoses of 93% of the 95 cultures were consistent with results of in vivo assays. This group of cytologic changes looks promising for further tests, analyses, and possible quantitation.
Ten-year survival of patients with small-cell lung cancer treated with combination chemotherapy with or without irradiation.
Authors: B E Johnson, J Grayson, R W Makuch, R I Linnoila, M J Anderson, M H Cohen, E Glatstein, J D Minna, D C Ihde
Journal: Journal of Clinical Oncology (1990)

We evaluated the 10- to 15-year outcome of 252 patients with small-cell lung cancer entered into therapeutic clinical trials with or without chest and cranial irradiation. Thirty-two patients (13%) survived free of cancer for 2 or more years. Twelve patients (5%) survived at least 10 years free of cancer, and 10 patients are currently alive and free of cancer beyond 10 years. Six of these 10 patients currently function at a level comparable with that before diagnosis. The other 22 patients who were cancer-free at 2 years have died. Nine patients died from recurrent small-cell lung cancer 2 to 6.2 years after initiation of chemotherapy. Five died from non-small-cell lung cancer, three died of other malignancies, and five died of causes other than cancer. A small fraction of patients with small-cell lung cancer are cured of their original malignancy, but these patients remain at high risk for second cancers and death from other causes.
Occupational exposure and lung function in a Dutch general population cohort
Authors: Kim de Jong, H. Marike Boezen, Hans Kromhout, Roel Vermeulen, Dirkje S. Postma, Judith M. Vonk
Journal: European Respiratory Journal (2012)

Background:

Occupational exposure to vapors, gases, dusts, fumes (VGDF) has been associated with lower lung function, with more pronounced effects in smokers. Less is known about occupational exposure to pesticides, solvents and heavy metals in relation to lung function. We assessed whether these agents negatively affect lung function in a general population cohort.

Methods:

We included 8,128 subjects aged 18-89 from the LifeLines cohort study (43% males). Occupational exposures (no/low/high) for current or last held job were estimated with the ALOHA+ Job Exposure Matrix. Associations between exposure and FEV1 were assessed using linear regression, adjusted for sex, age, height, weight, and smoking. Additionally we stratified for gender and smoking status.

Results:

Males were more often exposed than females. VGDF and pesticides had a negative dose-response effect on FEV1 (table 1). Effects were more pronounced in males and ever smokers.

Conclusion:

This study confirmed current knowledge on the detrimental effects of occupational VGDF exposure on lung function, especially in males and ever smokers. Additionally we show negative effects of pesticide exposure on lung function.

View this table:

Associations betweeen exposures and FEV1 (ml) (reference = no exposure)
Impact on overall survival of primary tumor extirpation in breast cancer patients who present with stage IV disease
Authors: J. E. Lang, R. Rao, L. Feng, F. Meric-Bernstam, I. Bedrosian, H. M. Kuerer, S. E. Singletary, K. K. Hunt, G. N. Hortobagyi, G. V. Babiera
Journal: Journal of Clinical Oncology (2007)

598 Background: Limited data exists regarding optimal local therapy for patients who present with stage IV breast cancer with an intact primary tumor. Two retrospective series, from the National Cancer Data Base and the Geneva Cancer Registry, showed that surgery may improve overall survival in these patients. Our institutional experience demonstrated improved metastatic progression-free survival after a median follow-up of 32.1 months but did not show a survival benefit at short term follow-up. We evaluated the impact of local control on overall (OS) and disease-specific survival (DSS) in this population after a longer follow-up interval to determine if a survival benefit could be demonstrated from local surgical treatment for selected patients with stage IV breast cancer. Methods: We reviewed the records of all patients at our institution who presented from 1997–2002 with stage IV disease with an intact primary tumor. OS and DSS were estimated by the Kaplan-Meier method. The log-rank test was used to compare the difference in survival between surgical and non-surgical patients. Multivariate statistical analysis was performed using the Cox proportional hazards model. Results: Of 220 patients identified with stage IV disease with an intact primary tumor, 80 (36%) underwent surgical resection of the primary tumor; 39 (49%) had segmental mastectomy and 41 (51%) had a total mastectomy. There were 140 (64%) patients who did not undergo surgery. The median follow-up duration from time of presentation to our institution was 58.6 months and the median OS time after presentation was 45.8 months. After adjustment for covariates, surgery was associated with improved OS (p=0.03) and DSS (p=0.04) compared to the non-surgical group. Conclusions: With a median follow-up time of 58.6 months, patients who presented with stage IV breast cancer with an intact primary tumor treated surgically had significantly improved OS and DSS compared to patients who did not undergo surgery. Our findings may be limited by a selection bias. Therefore, we feel that the issue of surgical intervention for the primary tumor in stage IV breast cancer patients deserves to be carefully studied in a well-designed, prospective, multi-center trial. No significant financial relationships to disclose.
The American Board of Psychiatry and Neurology: Looking Back and Moving Aheadedited by AminoffMichael J., M.D., D.Sc., F.R.C.P., and FaulknerLarry R., M.D. Washington, DC, American Psychiatric Publishing, 2012, 363 pp., $68.00.
Authors: Joanne H. Ritvo
Journal: American Journal of Psychiatry (2012)
Allergic Rhinitis in Danish General Practice
Authors: Poul A. Pedersen, Eva Rung Weeke
Journal: Allergy (1981)

The prevalence rate of allergic rhinitis and the consultation rate caused by this disease were studied in 131 general practices covering a population of 450,000 persons in Denmark. During a 1‐year period starting June 1977 all consultations with or without symptoms were recorded. Allergic rhinitis was defined as paroxysmal sneezing and rhinorrhoea with or without conjunctivitis, and without signs of infection. Results are presented from three groups of practices classified by self‐estimated completeness of reporting. 11–15 per thousand of the total population contacted a practice during the 1‐year period (males: 12–17%, females: 10–13%). The highest prevalence rate occurred at 10–19 years of age, and allergic rhinitis was common from five to 44 years of age. The prevalence rate was higher among males up to the age of 30, after which age it was a little higher among females. About two‐thirds of the patients consulting had at least one consultation per year with symptoms present. The number of contacts came to 4.4 per patient per year and 20–25% of these were with symptoms.
Iatrogenic isolated isoleucine deficiency as the cause of an acrodermatitis enteropathica-like syndrome
Authors: None Bosch, None Sillevis Smitt, None Van Gennip, None Abeling, None Schutgens, None Bakker, None Wijburg
Journal: British Journal of Dermatology (1998)

We present two patients with a suspected inborn error of metabolism. A female newborn presented with dysmorphic features and convulsions. Metabolic screening suggested a defect in isoleucine degradation. Within 2 weeks after the introduction of an isoleucine‐restricted diet, she developed a severe acrodermatitis enteropathica‐like syndrome. The plasma level of isoleucine was low with a normal leucine/isoleucine ratio. The second patient, a female infant deficient in leucine as a result of a leucine‐restricted diet, did not develop a dermatosis. Isoleucine is essential for normal growth and differentiation of keratinocytes and enterocytes. Deficiency of isoleucine, and not leucine or an imbalance in the leucine/isoleucine ratio, may result in an acrodermatitis enteropathica‐like syndrome.
Depressive Effect of Bone Marrow on the Yield of 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene-Induced Thymic Lymphomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J. K. Ball
Journal: JNCI Journal of the National Cancer Institute (1970)

Journal Article Depressive Effect of Bone Marrow on the Yield of 7,12-Dimethylbenz[a]anthracene-Induced Thymic Lymphomas Get access J. K. Ball J. K. Ball Cancer Research Laboratory, University of Western Ontario, London, Ontario, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 44, Issue 2, February 1970, Pages 439–445, https://doi.org/10.1093/jnci/44.2.439 Published: 01 February 1970 Article history Received: 18 September 1969 Accepted: 05 November 1969 Published: 01 February 1970
Bronchoscopic lung volume reduction with endobronchial valves for patients with heterogeneous emphysema and intact interlobar fissures (BeLieVeR-HIFi)
Authors: Claire Davey, Zaid Zoumot, William McNulty, Simon Jordan, Denis Carr, Michael Rubens, David Hansell, Michael Polkey, Pallav Shah, Nicholas Hopkinson
Journal: European Respiratory Journal (2014)

Background   Endobronchial valve (EBV) placement for patients with emphysema is effective in some individuals but overall group responses have been modest in clinical trials. We evaluated whether prospectively selecting patients with heterogeneous emphysema and intact interlobar fissures could improve outcomes.  The trial was supported by the NIHR EME program and registered (ISRCTN04761234).   Method   A double-blind randomised controlled trial comparing complete lobar occlusion with EBV against sham bronchoscopy.  Inclusion:(1) GOLD III or IV COPD with hyperinflation (TLC>100% & RV>150%) and limited exercise capacity (6 minute walk (6MW)   Primary endpoint was change in FEV 1  at 3 months.   Results   50 participants were randomised. Participants were well matched at baseline.  There were 2 deaths in the treatment arm (not related to EBV placement) and 1 patient in the control arm missed their final visit (in hospital with spontaneous pneumonthorax). Values for these 3 subjects were imputed.   Conclusion   This is the first prospective double-blind, randomised controlled trial of bronchoscopic therapy for emphysema to demonstrate clinically significant improvements in lung function.
Chemical Treatment of Tumors. V. Isolation of the Hemorrhage-Producing Fraction from &lt;italic&gt;Serratia marcescens (Bacillus prodigiosus)&lt;/italic&gt; Culture Filtrate&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: M. J. Shear, Floyd C. Turner, Adrien Perrault, Theresa Shovelton
Journal: JNCI Journal of the National Cancer Institute (1943)

Journal Article Chemical Treatment of Tumors. V. Isolation of the Hemorrhage-Producing Fraction from Serratia marcescens (Bacillus prodigiosus) Culture Filtrate Get access M. J. Shear, M. J. Shear principal biochemist Search for other works by this author on: Oxford Academic PubMed Google Scholar Floyd C. Turner, Floyd C. Turner senior surgeon Search for other works by this author on: Oxford Academic PubMed Google Scholar Adrien Perrault, Adrien Perrault technical assistance Search for other works by this author on: Oxford Academic PubMed Google Scholar Theresa Shovelton Theresa Shovelton National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 4, Issue 1, August 1943, Pages 81–97, https://doi.org/10.1093/jnci/4.1.81 Published: 01 August 1943
Inhibition of Cytochromes P-450 and Induction of Glutathione S-Transferases by Sulforaphane in Primary Human and Rat Hepatocytes
Authors: K Mahéo, F Morel, S Langouët, H Kramer, E Le Ferrec, B Ketterer, A Guillouzo
Journal: Cancer Research (1997)

The isothiocyanate sulforaphane (SF) is thought to be a potential chemoprotective agent. Its effects on Phase I and Phase II enzymes of carcinogen metabolism in primary cultures of rat and human hepatocytes have been investigated. Northern blot analyses of rat hepatocytes showed a dose-dependent induction of mRNAs for rat glutathione S-transferases (rGSTs) A1/A2 and P1 but not M1. This was associated with enhanced levels of not only rGSTA1, A2, A4, A5, and P1 but also of rGSTs M1 and M2. On the other hand, the enzyme activities in rat hepatocytes associated with cytochromes P-450 (CYPs) 1A1 and 2B1/2, namely ethoxyresorufin-O-deethylase and pentoxyresorufin-O-dealkylase, respectively, were decreased in a dose-dependent manner. In SF-treated human hepatocytes, hGSTA1/2 but not hGSTM1 mRNAs were induced, and the expression of CYP1A2 was unaffected, whereas the expression of CYP3A4, the major CYP in human liver, was markedly decreased at both mRNA and activity levels. These observations demonstrate that in intact human and rat hepatocytes, SF may both induce a number of GSTs and cause enzyme inhibition of some but not all CYPs and, in the case of CYP3A4, inhibit both its enzyme activity and its expression.
Early Failure of Titanium Alloy Femoral Components: A Quantitative Radiological Analysis of Osteolytic and Granulomatous Change
Authors: A J Unwin, P J Stiles
Journal: Journal of the Royal Society of Medicine (1993)

Shot blasted titanium alloy femoral components with a coarse finish were withdrawn from use in 1987 following reports of early component failure. We reviewed all coarse titanium femoral stems used in primary total hip arthroplasty in our institution between 1985 and 1987 and compared them to a similar stem made of vitallium which was also used over the same period. We found that, at an average of 5.2 years following implantation, over two-thirds of titanium components were associated with endosteal lysis. In many of the cases the early lytic changes were asymptomatic with significant bone loss occurring prior to presentation. We discuss our findings in relation to revision surgery. We advocate that all those with coarse stem titanium components should be positively reviewed to detect early lytic change before extensive bone destruction occurs.
Mild persistent asthma: a pragmatic approach.
Authors: W Perera
Journal: Thorax (2005)

▴ Boushey HA, Sorkness CA, King TS, et al . Daily versus as-needed corticosteroids for mild persistent asthma. N Engl J Med2005;352:1519–28

[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]



This randomised, three arm, parallel, year long study compared the treatment of mild persistent asthma with budesonide 200 μg bd, zafirlukast 20 mg bd, or no controller therapy. All patients were given a symptom based asthma treatment plan advising them to use open label budesonide or oral prednisone when their symptoms worsened. Patients …

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A cost optimization approach to occupational health screening for tuberculosis
Authors: Abiola Adanijo, Obadiah Elekima
Journal: European Respiratory Journal (2011)

Introduction: National UK guidelines recommend a two-staged screening process for Tuberculosis (TB) in new-entrants to the National Health Service using a chest radiograph (CXR), followed by a Mantoux test and or an Interferon Gamma Release Assay (IGRA) test. The IGRA test appears to be more cost-effective, with a higher sensitivity and specificity than the Mantoux test. Trials in community settings, using first line IGRA test, then CXR, have been more cost-effective compared to the guideline approach. Budgetary constraints necessitate allocating the existing screening resources judiciously.

Aim: To assess the effectiveness of first line IGRA test followed by CXR in TB screening.

Methods: A retrospective study of 246 new-entrant healthcare workers with risk factors for TB, based on symptoms, IGRA tests and CXR was undertaken. Criteria for Latent Tuberculosis Infection (LTBI) were positive IGRA test and a normal CXR.

Results: The prevalence of LTBI was 16.7%. CXRs were needed in 236 subjects. Only 128 (52%) had CXRs done, which did not show active TB; 87 of them had negative IGRA tests, and no documented risk factors for TB. The 108 that declined CXRs did not report any symptom of TB, and 105 of them had negative IGRA tests. Normal CXRs, within the preceding year, were associated with LTB1 (p<0.05). CXRs could have been avoided in the 192 subjects (81%) who had a negative IGRA tests had this test been done first.

Conclusion: The “IGRA test first” protocol is more cost-effective than a “CXR first protocol”, during TB screening, due to a reduction in the number of CXRs required. The presence of symptoms, a positive IGRA/Mantoux test, or risk factors for active TB should be indications for a CXR.
The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in small-cell lung cancer.
Authors: A F List, J D Hainsworth, B W Davis, K R Hande, F A Greco, D H Johnson
Journal: Journal of Clinical Oncology (1986)

Review of clinical data from 350 patients with small-cell lung cancer (SCLC) revealed hyponatremia (sodium less than 130 mEq/L) attributable to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in 40 patients (11%). Although hyponatremia was severe in most instances (median, sodium 117 mEq/L), symptoms attributable to water intoxication were identified in only 27% of hyponatremic episodes. Development of SIADH showed no correlation with clinical stage, distribution of metastatic sites, sex, or histologic subtype of small-cell carcinoma. SIADH occurred most often with initial presentation (33 of 40), and resolved promptly (less than 3 weeks) with initiation of combination chemotherapy in 80% of evaluable patients. The presence of SIADH did not influence response to chemotherapy or overall survival as an independent variable. However, in five patients profound hyponatremia developed immediately following primary cytotoxic therapy (range, one to five days). Despite initial control of SIADH, dilutional hyponatremia recurred in 70% of patients with tumor progression. Our findings suggest that development of clinically demonstrable SIADH in patients with SCLC is dependent on functional properties of the neoplastic cells, rather than tumor burden or metastatic site. The potential for development of clinically significant hyponatremia early in the course of cytotoxic therapy emphasizes the need to closely monitor patients, particularly those receiving chemotherapy regimens requiring substantial intravenous hydration.
Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1)
Authors: Kim Papp, Kristian Reich, Craig L. Leonardi, Leon Kircik, Sergio Chimenti, Richard G.B. Langley, ChiaChi Hu, Randall M. Stevens, Robert M. Day, Kenneth B. Gordon, Neil J. Korman, Christopher E.M. Griffiths
Journal: Journal of the American Academy of Dermatology (2015)