tbuckley/cabot-search huggingface dataset:
Mortality risks of COPD for nonsmokers and smokers from a prospective cohort study of 390,269 subjects in Taiwan - Assessing involvement beyond the lungs
Authors: Wei-Erh Cheng, Chi-Pang Wen, Min-Kwang Tsai, Yi-Chen Yang, Xifeng Wu
Journal: European Respiratory Journal (2012)

Background   COPD is known to increase mortality in respiratory diseases, but is less known for its extra-pulmonary and lung cancer effect, particularly among nonsmokers   Objectives   To assess the risks of COPD subjects among smokers and nonsmokers and to quantify its mortality effect beyond the lungs.   Method   The cohort consisted of 390,269 adults, between 1994 and 2008, went through a fee-for-service, standard panel of health screening program. COPD was defined by Gold criteria. Mortality and cancer incidence were identified in an average of 8.5 years of follow-up. Cox proportionate model was used to calculate the hazard ratios (HR)   Results   More men (4.6%) than women (3.8%) and more smokers (5.3%) than nonsmokers (3.7%) had COPD, with a mean age of 50. The excess all-cause mortality for smokers (HR: 2.51) was three times larger than nonsmokers (HR: 1.53), when compared to those without COPD. Not only smokers (4.5-fold) but also nonsmokers (1.4-fold) had lung cancer mortality significantly increased, implying the independent effect from COPD. Other than lung cancer and respiratory diseases, COPD had increased risks for CVD (HR: 1.76), including ischemic heart disease (HR: 1.63) and stroke (HR: 1.80), and kidney diseases (HR: 2.32). The extra-pulmonary causes constituted 77% for non-smokers and 58% for smokers.  Conclusion  Three quarters of the excess deaths among nonsmoking COPD subjects died from causes beyond the lungs. They had increases in stroke, heart, renal and infectious diseases, in addition to lung cancer. These extra-pulmonary risks, under-appreciated by clinicians and unaware of by the patients, are major challenges to overcome.
Transcytosis of Retinol-Binding Protein across Renal Proximal Tubule Cells after Megalin (gp 330)-Mediated Endocytosis
Authors: MICHELE MARINÓ, DAVID ANDREWS, DENNIS BROWN, ROBERT T. McCLUSKEY
Journal: Journal of the American Society of Nephrology (2001)

Plasma retinol-binding protein (RBP) combined with vitamin A (retinol) is partially filtered through the glomerulus and then absorbed by proximal tubule cells, leading to recycling of retinol to the circulation. Recently, it was shown that reabsorption of RBP-retinol complexes by proximal tubule cells is mediated by megalin (gp 330), an apical endocytic receptor. It was proposed that RBP is transported by megalin to lysosomes, where it is degraded, thus liberating retinol, which then combines with newly synthesized RBP to be secreted into the bloodstream. This study shows that passage of RBP through immortalized rat renal proximal tubule (IRPT) cells occurs by transcytosis after megalin-mediated endocytosis, which provides an alternative pathway for recycling of retinol. IRPT cells cultured as polarized monolayers with tight junctions were used on permeable filters in the upper chamber of dual-chambered devices, with megalin expression exclusively on the upper surface. After addition of RBP to the upper chamber and incubation at 37 degrees C, intact RBP was found in fluids that were collected from the lower chamber. In contrast, control substances (mannitol, lysozyme, albumin, and glutathione-S-transferase) were not appreciably transported across IRPT cells, indicating that passage of RBP was by transcytosis and not by paracellular leakage. Confocal microscopy analysis of IRPT cells after addition of RBP to the upper chamber revealed RBP-containing granules at the apical membrane, subapically, and also at basolateral membranes. When RBP was added to IRPT cells together with megalin competitors, the amount of transcytosed RBP was markedly reduced. We also found that some RBP was internalized and degraded by IRPT cells, but this process was not appreciably affected by megalin competitors, indicating that RBP endocytosed by megalin was not transported to lysosomes and degraded but rather transcytosed across IRPT cells.
Patients' opinion for their inhalation device. An assessment of convenience and use
Authors: Katerina Papataxiarchou, Katerina Athanassiou
Journal: European Respiratory Journal (2013)

Introduction:   New inhalation devices are introduced for pulmonary diseases. FSI-10 questionnaire is a tool for assessment patients’ satisfaction. It is valid and reliable in many languages and used extensively by physicians in research and clinical practice.   Aims and objectives:   This is a study to evaluate patients’ opinion regarding a recently introduced device named ‘Elpenhaler®. In addition to questionnaire’s standard context patients were asked to emphasize in device’s benefits and disadvantages.   Methods:   The study has been conducted according to legislation and Good Pharacoepidemiology Practice guidelines. It was undertaken to assess the handling of device in real life. 4312(59,5% males) aged 58,5± 15,2 evaluated their device. Diagnosis: COPD 58,6%(1821 males), asthma 37,3%(927 females), both diseases 1,8%.   Results:   FSI-10 achieved total score 44,2±4,8 (min 16-max 50). 1152 patients(26,7%) pointed out specific advantages: 769(66,8%) evaluated the device as convenient-easy to use, 170(14,8%) emphasized to correct drug administration and 107(9,3%) linked device with drug delivery and hence disease control. 331(7,7%) pointed out specific disadvantages: 106(32%) found the device difficult to use, 140(42,3%) inconvenient and 50(15,1%) linked the device with adverse events occurred during the treatment period. No remarkable differences were recorded between opinions by gender. No safety issues reported during study duration.   Conclusions:   These results suggest that patients are able to assess their inhalation device. This can be further evaluated to define the most appropriate method of selecting an inhaler for a patient, taking into account continued education in proper use and treatment efficacy.
Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality
Authors: Edgar R. Miller, Roberto Pastor-Barriuso, Darshan Dalal, Rudolph A. Riemersma, Lawrence J. Appel, Eliseo Guallar
Journal: Annals of Internal Medicine (2005)

Background: Experimental models and observational studies suggest that vitamin E supplementation may prevent cardiovascular disease and cancer. However, several trials of high-dosage vitamin E supplementation showed non–statistically significant increases in total mortality. Purpose: To perform a meta-analysis of the dose–response relationship between vitamin E supplementation and total mortality by using data from randomized, controlled trials. Patients: 135 967 participants in 19 clinical trials. Of these trials, 9 tested vitamin E alone and 10 tested vitamin E combined with other vitamins or minerals. The dosages of vitamin E ranged from 16.5 to 2000 IU/d (median, 400 IU/d). Data Sources: PubMed search from 1966 through August 2004, complemented by a search of the Cochrane Clinical Trials Database and review of citations of published reviews and meta-analyses. No language restrictions were applied. Data Extraction: 3 investigators independently abstracted study reports. The investigators of the original publications were contacted if required information was not available. Data Synthesis: 9 of 11 trials testing high-dosage vitamin E (≥400 IU/d) showed increased risk (risk difference > 0) for all-cause mortality in comparisons of vitamin E versus control. The pooled all-cause mortality risk difference in high-dosage vitamin E trials was 39 per 10 000 persons (95% CI, 3 to 74 per 10 000 persons; P = 0.035). For low-dosage vitamin E trials, the risk difference was −16 per 10 000 persons (CI, −41 to 10 per 10 000 persons; P > 0.2). A dose–response analysis showed a statistically significant relationship between vitamin E dosage and all-cause mortality, with increased risk of dosages greater than 150 IU/d. Limitations: High-dosage (≥400 IU/d) trials were often small and were performed in patients with chronic diseases. The generalizability of the findings to healthy adults is uncertain. Precise estimation of the threshold at which risk increases is difficult. Conclusion: High-dosage (≥400 IU/d) vitamin E supplements may increase all-cause mortality and should be avoided.
Double-Blind Treatment of Major Depression With Dehydroepiandrosterone
Authors: Owen M. Wolkowitz, Victor I. Reus, Audrey Keebler, Nicola Nelson, Mirit Friedland, Louann Brizendine, Eugene Roberts
Journal: American Journal of Psychiatry (1999)

This study was designed to assess possible antidepressant effects of dehydroepiandrosterone (DHEA), an abundant adrenocortical hormone in humans.Twenty-two patients with major depression, either medication-free or on stabilized antidepressant regimens, received either DHEA (maximum dose = 90 mg/day) or placebo for 6 weeks in a double-blind manner and were rated at baseline and at the end of the 6 weeks with the Hamilton Depression Rating Scale. Patients previously stabilized with antidepressants had the study medication added to that regimen; others received DHEA or placebo alone.DHEA was associated with a significantly greater decrease in Hamilton depression scale ratings than was placebo. Five of the 11 patients treated with DHEA, compared with none of the 11 given placebo, showed a 50% decrease or greater in depressive symptoms.These results suggest that DHEA treatment may have significant antidepressant effects in some patients with major depression. Further, larger-scale trials are warranted.
Cisplatin, vinblastine, and hydrazine sulfate in advanced, non-small-cell lung cancer: a randomized placebo-controlled, double-blind phase III study of the Cancer and Leukemia Group B.
Authors: M P Kosty, S B Fleishman, J E Herndon, K Coughlin, A B Kornblith, A Scalzo, J C Morris, J Mortimer, M R Green
Journal: Journal of Clinical Oncology (1994)

PURPOSE To assess the chemotherapy regimen of cisplatin, vinblastine, and hydrazine sulfate administered to patients with non-small-cell lung cancer (NSCLC) in a randomized, placebo-controlled double-blind phase III study. PATIENTS AND METHODS Between July 25, 1989 and February 1, 1991, 291 patients with stage IIIB or IV NSCLC and performance status 0 or 1 were randomized to receive cisplatin 100 mg/m2 intravenously (IV) every 28 days, vinblastine 5 mg/m2 IV per week times five, then every 2 weeks; and either hydrazine sulfate 60 mg three times per day orally or placebo. The concurrent use of corticosteroids, medroxyprogesterone, or other appetite stimulants was not permitted. Treatment groups were comparable for known prognostic variables. The primary end point of this study was survival; however, the influence of hydrazine sulfate on nutritional status, performance status, and quality of life was also assessed. RESULTS Analysis of 266 eligible patients showed a median survival duration of 7.78 months for the hydrazine sulfate-treated group compared with 7.70 months for the placebo-treated group (P = .65, log-rank). Objective response rates were similar for the two groups, with 4% complete responses, 20% partial responses, and 2% regressions in those treated with hydrazine sulfate; 3% complete responses, 23% partial responses, and 2% regressions in those who received placebo. The major toxicity was severe or life-threatening neutropenia, which occurred in 65% of hydrazine sulfate patients and 63% of placebo patients. There were no differences noted between the two groups in degree of anorexia, weight gain or loss, or overall nutritional status. Sensory and motor neuropathy occurred significantly more often in patients treated with hydrazine sulfate. Quality of life was significantly worse in patients who received hydrazine sulfate. CONCLUSION This study suggests no benefit from the addition of hydrazine sulfate to an effective cytotoxic regimen.
Selenium Inhibition of &lt;italic&gt;N&lt;/italic&gt;-Methyl-&lt;italic&gt;N&lt;/italic&gt;-nitrosourea-Induced Mammary Carcinogenesis in the Rat&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;, &lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;, &lt;xref ref-type="fn" rid="fn4"&gt;4&lt;/xref&gt;
Authors: H J Thompson, P J Becci
Journal: JNCI Journal of the National Cancer Institute (1980)

The effect of supplemental dietary selenium on the postinitiation state of N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis was investigated in noninbred female Sprague-Dawley rats. Mammary cancer was induced by a single iv injection of MNU. Supplemental selenium feeding was begun 7 days after carcinogen treatment. Feeding of selenium prolonged the latency of mammary cancer appearance and resulted in a reduction in the average number of cancers per rat. The results suggested an inhibitory effect of pharmacologic levels of dietary selenium on the postinitiation stage of mammary carcinogenesis.
Contrasting Roles for Orbitofrontal Cortex and Amygdala in Credit Assignment and Learning in Macaques
Authors: Bolton K.H. Chau, Jérôme Sallet, Georgios K. Papageorgiou, MaryAnn P. Noonan, Andrew H. Bell, Mark E. Walton, Matthew F.S. Rushworth
Journal: Neuron (2015)
Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer--report of a Canadian multicenter randomized trial.
Authors: E Rapp, J L Pater, A Willan, Y Cormier, N Murray, W K Evans, D I Hodson, D A Clark, R Feld, A M Arnold
Journal: Journal of Clinical Oncology (1988)

The survival benefit of combination chemotherapy to patients with advanced non-small-cell carcinoma of the lung (NSCLC) is controversial. To study this question, the National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a prospective randomized trial comparing best supportive care (BSC) to two chemotherapy regimens, vindesine and cisplatin (VP), and cyclophosphamide, doxorubicin, and cisplatin (CAP). Between February 1983 and January 1986, 23 centers across Canada entered 251 patients on study. Eighteen centers participated in the three-arm schema (150 patients); centers choosing not to participate in a study with a no-chemotherapy arm followed a two-arm schema comparing VP with CAP (101 additional patients). Altogether, 233 patients were eligible. Patients had measurable or evaluable disease, with either distant metastases (82.5%) or bulky limited disease considered inoperable or unsuitable for radical radiotherapy. The treatment groups were comparable in terms of age, sex, performance status, histology, disease extent, and weight loss. The overall response rates (complete response [CR] plus partial response [PR]) on the chemotherapy arms were CAP, 15.3%, and VP, 25.3% (P = .06). Patients on the three-arm portion of the trial had a median survival of 32.6 weeks when treated with VP, 24.7 weeks with CAP, and 17 weeks with BSC. The significance of the differences in survival, adjusted for prognostic factors, is as follows: chemotherapy v BSC, P = .02; VP v BSC, P = .01; and CAP v BSC, P = .05. Toxicity on the chemotherapy arms was significant, with leukopenia of severe or greater degree occurring in 37.8% (CAP) and 40.0% (VP), severe vomiting in 12.2% (CAP) and 23.3% (VP), and severe neurotoxicity in 15.6% (VP).
Physiology and Practice of Pulmonary Function
Authors: V. Brusasco
Journal: European Respiratory Journal (2010)

Edited by J.M.B. Hughes    Published by the Association for Respiratory Technology and Physiology (ARTP), UK    Pages: 323. Price: £24.95. ISBN: 978-0-9536898-5-9

The knowledge of respiratory physiology has progressed considerably in recent decades. However, the current tendency in clinical practice has been to restrict pulmonary function testing to simple spirometry, while most of the advanced methods have been considered as unnecessary or even esoteric. This has probably been due to a growing enthusiasm towards easy-to-measure biological markers, …
Effects of Perinatal Progesterone on Mouse Mammary Differentiation In Vitro: Brief Communication 2 3
Authors: M. R. Warner
Journal: JNCI Journal of the National Cancer Institute (1978)

The effects of perinatal injection of progesterone on hormone sensitivity of mammary glands to the induction of lobules were investigated after in vivo pretreatment and subsequent organ culture. The mammary tissues of C57BL/Crgl mice given injections of 100 μg progesterone on each of the first 5 days of life and those of un inoculated controls were organ cultured on week 4 of life after 4, 6, or 9 days of pretreatment injections (1 μg 17β-estradiol plus 1 mg progesterone). The effects of several hormone supplements to the chemically defined culture medium were assessed. Lobular development was similar in tissues of mice given injections of progesterone perinatally and their controls after in vivo pretreatment; after culture with 17β-estradiol, progesterone, aldosterone, growth hormone, prolactin, insulin, and thyroxine; or after culture with insulin and thyroxine. Lobular development was enhanced after 6 but not after 9 days of pretreatment followed by culture with 17β-estradiol, progesterone, aldosterone, insulin, and thyroxine. Alveolar but not lobular development was enhanced in tissues from mice given injections of progesterone perinatally after 9 days of pretreatment followed by culture with insulin and thyroxine. Perinatal injection of progesterone, a treatment previously reported to promote mammary tumorigenesis in mice, did not uniformly influence in vitro lobular differentiation of their mammary glands. These results are in contrast to our previous finding that perinatal injection of estrogen in mice, a treatment that is also tumorigenic in the mammary glands, does increase in vitro lobular differentiation in response to mammotropic hormones. Life events subsequent to neonatal exposure may be necessary to promote the expression of tumorigenic potential in the mammary tissues of mice given injections of progesterone neonatally.
Effect of Noninvasive Ventilation vs Oxygen Therapy on Mortality Among Immunocompromised Patients With Acute Respiratory Failure
Authors: Virginie Lemiale, Djamel Mokart, Matthieu Resche-Rigon, Frédéric Pène, Julien Mayaux, Etienne Faucher, Martine Nyunga, Christophe Girault, Pierre Perez, Christophe Guitton, Kenneth Ekpe, Achille Kouatchet, Igor Théodose, Dominique Benoit, Emmanuel Canet, François Barbier, Antoine Rabbat, Fabrice Bruneel, Francois Vincent, Kada Klouche, Kontar Loay, Eric Mariotte, Lila Bouadma, Anne-Sophie Moreau, Amélie Seguin, Anne-Pascale Meert, Jean Reignier, Laurent Papazian, Ilham Mehzari, Yves Cohen, Maleka Schenck, Rebecca Hamidfar, Michael Darmon, Alexandre Demoule, Sylvie Chevret, Elie Azoulay
Journal: JAMA (2015)

for the Groupe de Recherche en Réanimation Respiratoire du patient d'Onco-Hématologie (GRRR-OH) IMPORTANCE Noninvasive ventilation has been recommended to decrease mortality among immunocompromised patients with hypoxemic acute respiratory failure.However, its effectiveness for this indication remains unclear.OBJECTIVE To determine whether early noninvasive ventilation improved survival in immunocompromised patients with nonhypercapnic acute hypoxemic respiratory failure.
Ventilatory responsiveness to carbon dioxide below the normal control point in conscious normoxic humans
Authors: A R Cummin, V S Sidhu, R J Telford, K B Saunders
Journal: European Respiratory Journal (1992)

A recently developed CO2 pulse technique was used to test for ventilatory sensitivity to CO2 in four normal men following 2 min voluntary hyperventilation down to an end-tidal CO2 tension (PETCO2) of 20 mmHg (2.7 kPa). Pure CO2 was injected into the inspiratory limb of a breathing circuit at 0.4 l.min-1 for 30 s and any small ventilatory response was detected against background noise by ensemble-averaging of multiple runs. Following hyperventilation, ventilation was initially often above control and apnoea was not seen. In one subject, the ventilatory response to the CO2 pulse was barely detectable either before or after hyperventilation. In another subject, there was a response to pulses given before hyperventilation and 3 and 5.5 min after hyperventilation but not 30 s after hyperventilation when PETCO2 was about 25 mmHg (3.3 kPa) and rising. In the two remaining subjects ventilatory responses were seen to CO2 pulses started 30 s after hyperventilation, although PETCO2 following the pulse remained some 5 mmHg (0.7 kPa) below baseline. We conclude that in some subjects the PETCO2 threshold lies well below the normal PETCO2. The technique is tedious for the experimental subject because of the large number of repetitions required and, therefore, unsuitable for a study on a large number of subjects.
Simplification of local therapy of psoriasis with 8-methoxypsoralen.
Authors: HANS SCHAEFER, KLAUS VIVELL, VERENA KENTSCH, WOLFGANG SCHALLA, SCHWANHILD JENNY
Journal: British Journal of Dermatology (1976)

Local 8‐methoxypsoralen black‐light treatment was carried out on sixty‐two patients. For the first time, oil was employed as a preparation base in order to increase the transparency and so the effectiveness of irradiation. Also the need for a descaling pretreatment was avoided. In investigations still being carried out, 27.5% patients showed very good improvement, 48.4% good and 24.2% unsatisfactory results of treatment. In many cases, less than fifteen irradiation sessions were necessary for clinical healing. However, to obtain a uniform pigmentation, additional irradiation proved necessary.
On the Orthomolecular Environment of the Mind: Orthomolecular Theory
Authors: LINUS PAULING
Journal: American Journal of Psychiatry (1974)

The author defines orthomolecular psychiatry as the achievement and preservation of good mental health by the provision of the optimum molecular environment for the mind, especially the optimum concentrations of substances normally present in the human body, such as the vitamins. He states that there is sound evidence for the theory that increased intake of such vitamins as ascorbic acid, niacin, pyridoxine, and cyanocobalamin is useful in treating schizophrenia. The negative conclusions of APA Task Force Report 7, Megavitamin and Orthomolecular Therapy in Psychiatry, he says, result not only from faulty arguments and from a bias against megavitamin therapy but also from a failure to deal fully with orthomolecular therapy in psychiatry. Three psychiatrists comment on Dr. Pauling's presentation.