tbuckley/cabot-search huggingface dataset:
IL‐4 fails to regulate<i>in vitro</i>beryllium-induced cytokines in berylliosis
Authors: L.A. Maier, R.T. Sawyer, S.S. Tinkle, L.A. Kittle, E.A. Barker, R. Balkissoon, C. Rose, L.S. Newman
Journal: European Respiratory Journal (2001)

Bronchoalveolar lavage (BAL) cells from patients with chronic beryllium disease (CBD) have been used to evaluate the beryllium-specific immune response and potential immunotherapeutics. Beryllium induces interferon‐γ (IFN‐γ), interleukin‐2 (IL‐2), tumour necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6) and interleukin‐10 (IL‐10) from BAL cells. An antibody to IL‐2 and recombinant human (rHu) IL‐10 is able to partially suppress the beryllium-stimulated immune response. To obtain BAL cells, bronchoscopy is required, providing risk to the patient and a limited number of cells to study the immune response. As a result, the objectives of the study were to determine 1) whether CBD peripheral blood mononuclear cells (PBMNs) stimulated with beryllium would produce a similar cytokine pattern as BAL cells, and 2) whether this response could be modulated by interleukin‐4 (IL‐4), an immunomodulatory cytokine. CBD and normal individuals' PBMN and BAL cells were stimulated with and without beryllium sulfate. To modulate this antigen-stimulated response, we added rHu IL‐4 to the unstimulated and beryllium-stimulated cells. IFN‐γ, IL‐2, TNF‐α, IL‐6 and IL‐10 cytokine concentrations were determined from cell supernatants by enzyme-linked immunosorbent assays (ELISA), while IL‐4 messenger ribonucleic acid (mRNA) was assessed using polymerase chain reaction (PCR). Beryllium did not stimulate any of these cytokines from normal PBMNs. Increasing levels of IL‐6 and TNF‐α were produced constituitively by CBD PBMNs over time. Compared to the unstimulated CBD PBMNs, beryllium stimulated significant IFN‐γ, TNF‐α, IL‐2, IL‐6 and IL‐10 production. This response was similar to that stimulated from CBD BAL cells, although of a much lower magnitude. Low levels of IL‐4 mRNA were found in CBD and control PBMNs, which were not increased with beryllium stimulation. The beryllium-stimulated cytokine levels were not decreased by the addition of IL‐4. IL‐4 was unable to downregulate any of these beryllium-stimulated cytokines from CBD BAL cells or increase IL‐4 mRNA from either CBD PBMN or BAL cells, and thus is an unlikely immunomodulatory agent in CBD. From the data, it was concluded that chronic beryllium disease peripheral blood mononuclear cells provide a model to study the beryllium-stimulated immune response. Interleukin‐4's inability to downregulate any of the beryllium-stimulated cytokines makes it an unlikely therapeutic candidate in chronic beryllium disease.
EULAR points to consider in the development of classification and diagnostic criteria in systemic vasculitis
Authors: N. Basu, R. Watts, I. Bajema, B. Baslund, T. Bley, M. Boers, P. Brogan, L. Calabrese, M. C. Cid, J. W. Cohen-Tervaert, L. F. Flores-Suarez, S. Fujimoto, K. de Groot, L. Guillevin, G. Hatemi, T. Hauser, D. Jayne, C. Jennette, C. G. M. Kallenberg, S. Kobayashi, M. A. Little, A. Mahr, J. McLaren, P. A. Merkel, S. Ozen, X. Puechal, N. Rasmussen, A. Salama, C. Salvarani, C. Savage, D. G. I. Scott, M. Segelmark, U. Specks, C. Sunderkoetter, K. Suzuki, V. Tesar, A. Wiik, H. Yazici, R. Luqmani
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objectives</h3> The systemic vasculitides are multiorgan diseases where early diagnosis and treatment can significantly improve outcomes. Robust nomenclature reduces diagnostic delay. However, key aspects of current nomenclature are widely perceived to be out of date, these include disease definitions, classification and diagnostic criteria. Therefore, the aim of the present work was to identify deficiencies and provide contemporary points to consider for the development of future definitions and criteria in systemic vasculitis. <h3>Methods</h3> The expert panel identified areas of concern within existing definitions/criteria. Consequently, a systematic literature review was undertaken looking to address these deficiencies and produce 'points to consider' in accordance with standardised European League Against Rheumatism (EULAR) operating procedures. In the absence of evidence, expert consensus was used. <h3>Results</h3> There was unanimous consensus for re-evaluating existing definitions and developing new criteria. A total of 17 points to consider were proposed, covering 6 main areas: biopsy, laboratory testing, diagnostic radiology, nosology, definitions and research agenda. Suggestions to improve and expand current definitions were described including the incorporation of anti-neutrophil cytoplasm antibody and aetiological factors, where known. The importance of biopsy in diagnosis and exclusion of mimics was highlighted, while equally emphasising its problems. Thus, the role of alternative diagnostic tools such as MRI, ultrasound and surrogate markers were also discussed. Finally, structures to develop future criteria were considered. <h3>Conclusions</h3> Limitations in current classification criteria and definitions for vasculitis have been identified and suggestions provided for improvement. Additionally it is proposed that, in combination with the updated evidence, these should form the basis of future attempts to develop and validate revised criteria and definitions of vasculitis.
Radiographically occult lung cancer treated with fibreoptic bronchoscopic electrocautery: a pilot study of a simple and inexpensive technique
Authors: TJ van Boxem, BJ Venmans, FM Schramel, JC van Mourik, RP Golding, PE Postmus, TG Sutedja
Journal: European Respiratory Journal (1998)

The curative potential of bronchoscopic intervention, e.g. photodynamic therapy (PDT) and brachytherapy, for resectable radiographically occult lung cancer has been reported previously. Bronchoscopic electrocautery is currently feasible using an insulated flexible bronchoscope to coagulate and vaporize tumour tissue. Since the lesions are usually small, noninvasive bronchoscopic electrocautery may be able to eradicate radiographically occult lung cancer completely. In a prospective study, 13 patients with 15 radiographically occult lung cancer lesions were treated with bronchoscopic electrocautery. The duration of follow-up was &gt; or = 16 months. The median age of the patients was 69 yrs (range 48-79 yrs). Fibreoptic bronchoscopy under local anaesthesia was used to coagulate the occult lung cancer. Approximately 30 W of energy was applied until visible necrosis of the tumour area became apparent. There were no immediate complications. In 10 patients with 12 lesions, a complete response (CR) was obtained (CR rate 80%; 95% confidence interval (95% CI) 52-96%). Median duration of follow-up was 21 months (range 16-43 months). Bronchoscopic electrocautery did not obtain a CR in the remaining three patients, but PDT also failed to achieve CR. Two patients underwent radical resection, and the tumours were histologically confirmed to be more invasive. One patient received external radiotherapy. Three patients with a CR died during follow-up, two as a result of myocardial infarction and apoplexy, and one because of metastasis from his previously resected T3N1 primary large cell cancer. Current data show bronchoscopic electrocautery to be equally effective and potentially as curative as photodynamic therapy for treating patients with radiographically occult lung cancer. Obvious advantages are that it is an inexpensive and simple procedure, which does not cause photosensitivity.
Comparative intrauterine development and placental function of ART concepti: implications for human reproductive medicine and animal breeding
Authors: Enrrico Bloise, Sky K. Feuer, Paolo F. Rinaudo
Journal: Human Reproduction Update (2014)

The number of children conceived using assisted reproductive technologies (ART) has reached >5 million worldwide and continues to increase. Although the great majority of ART children are healthy, many reports suggest a forthcoming risk of metabolic complications, which is further supported by the Developmental Origins of Health and Disease hypothesis of suboptimal embryo/fetal conditions predisposing adult cardiometabolic pathologies. Accumulating evidence suggests that fetal and placental growth kinetics are important features predicting post-natal health, but the relationship between ART and intrauterine growth has not been systematically reviewed. Relevant studies describing fetoplacental intrauterine phenotypes of concepti generated by in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and somatic cell nuclear transfer (SCNT) in the mouse, bovine and human were comprehensively researched using PubMed and Google Scholar. Intrauterine growth plots were created from tabular formatted data available in selected reports. ART pregnancies display minor but noticeable alterations in fetal and placental growth curves across mammalian species. In all species, there is evidence of fetal growth restriction in the earlier stages of pregnancy, followed by significant increases in placental size and accelerated fetal growth toward the end of gestation. However, there is a species-specific effect of ART on birthweights, that additionally vary in a culture condition-, strain-, and/or stage at transfer-specific manner. We discuss the potential mechanisms that underlie these changes, and how they are affected by specific components of ART procedures. ART may promote measurable alterations to intrauterine growth trajectory and placental function. Key findings include evidence that birthweight is not a reliable marker of fetal stress, and that increases in embryo manipulation result in more deviant fetal growth curves. Because growth kinetics in early life are particularly relevant to adult metabolic physiology, we advise more rigorous assessment of fetal growth and placental function in human ART pregnancies, as well as continued follow-up of ART offspring throughout post-natal life. Finally, strategies to minimize embryo manipulations should be adopted whenever possible.
Randomized Placebo-Controlled Trial of Cognitive Behavioral Therapy and Armodafinil for Insomnia After Cancer Treatment
Authors: Joseph A. Roscoe, Sheila N. Garland, Charles E. Heckler, Michael L. Perlis, Anita R. Peoples, Michelle Shayne, Josée Savard, Nina P. Daniels, Gary R. Morrow
Journal: Journal of Clinical Oncology (2014)

Purpose Insomnia is a distressing and often persisting consequence of cancer. Although cognitive behavioral therapy for insomnia (CBT-I) is the treatment of choice in the general population, the use of CBT-I in patients with cancer is complicated, because it can result in transient but substantial increases in daytime sleepiness. In this study, we evaluated whether CBT-I, in combination with the wakefulness-promoting agent armodafinil (A), results in better insomnia treatment outcomes in cancer survivors than CBT-I alone. Patients and Methods We report on a randomized trial of 96 cancer survivors (mean age, 56 years; female, 87.5%; breast cancer, 68%). The primary analyses examined whether ≥ one of the 7-week intervention conditions (ie, CBT-I, A, or both), when compared with a placebo capsule (P) group, produced significantly greater clinical gains. Insomnia was assessed by the Insomnia Severity Index and sleep quality by the Pittsburgh Sleep Quality Inventory. All patients received sleep hygiene instructions. Results Analyses controlling for baseline differences showed that both the CBT-I plus A (P = .001) and CBT-I plus P (P = .010) groups had significantly greater reductions in insomnia severity postintervention than the P group, with effect sizes of 1.31 and 1.02, respectively. Similar improvements were seen for sleep quality. Gains on both measures persisted 3 months later. CBT-I plus A was not significantly different from CBT-I plus P (P = .421), and A alone was not significantly different from P alone (P = .584). Conclusion CBT-I results in significant and durable improvements in insomnia and sleep quality. A did not significantly improve the efficacy of CBT-I or independently affect insomnia or sleep quality.
Association of Leukocyte Telomere Length With Circulating Biomarkers of the Renin-Angiotensin-Aldosterone System
Authors: Ramachandran S. Vasan, Serkalem Demissie, Masayuki Kimura, L. Adrienne Cupples, Nader Rifai, Charles White, Thomas J. Wang, Jeffrey P. Gardner, Xiaogian Cao, Emelia J. Benjamin, Daniel Levy, Abraham Aviv
Journal: Circulation (2008)

Leukocyte telomere length (LTL) chronicles the cumulative burden of oxidative stress and inflammation over a life course. Activation of the renin-angiotensin-aldosterone system is associated with increased oxidative stress and inflammation. Therefore, LTL may be related to circulating biomarkers of the renin-angiotensin-aldosterone system.We evaluated the cross-sectional relations of LTL (dependent variable) to circulating renin and aldosterone concentrations and the renin-to-aldosterone ratio (all logarithmically transformed; independent variables) in 1203 Framingham Study participants (mean age, 59 years; 51% women). We used multivariable linear regression and adjusted for age, blood pressure, hypertension treatment, smoking, diabetes mellitus, body mass index, hormone replacement therapy, serum creatinine, and the urine sodium-to-creatinine ratio. Overall, multivariable-adjusted LTL was inversely related to renin (beta coefficient per unit increase, -0.038; P=0.036), directly related to aldosterone (beta=0.099; P=0.002), and inversely related to the renin-to-aldosterone ratio (beta=-0.049; P=0.003). Relations of LTL to biomarkers were stronger in those with hypertension, although a formal test of interaction was not statistically significant (P=0.20). Individuals with hypertension displayed significant associations of LTL with renin (beta=-0.060; P=0.005), aldosterone (beta=0.134; P=0.002), and renin-to-aldosterone ratio (beta=-0.072; P<0.001). Participants with hypertension who were in the top tertile of the renin-to-aldosterone ratio had LTL that was 182 base pairs shorter relative to those in the lowest tertile.In our community-based sample, LTL was shorter in individuals with a higher renin-to-aldosterone ratio, especially in participants with hypertension. Additional investigations are warranted to confirm our observations.
Season of Birth Among Patients With Schizophrenia and Their Siblings: Evidence for the Procreational Habits Hypothesis
Authors: Jaana M. Suvisaari, Jari K. Haukka, Jouko K. Lönnqvist
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The birth rate of patients with schizophrenia during the winter and spring months is 5%–8% higher worldwide than the birth rate of the general population in the winter and spring months. Seasonal variation of births among the unaffected siblings of patients with schizophrenia has not been studied with adequate sample sizes. The authors investigated the seasonal variation of births among siblings of patients with schizophrenia in a large, nationwide, representative patient and sibling population. METHOD: Finnish patients with schizophrenia born from 1950 to 1969 (N=15,389) were identified from three nationwide health care registers. Unaffected siblings of these patients born in the same time period (N=37,819) were identified from the Finnish National Population Register. The seasonal variation of births among patients and siblings were examined by using a log-linear model. Explanatory variables were sex, year of birth categorized into four 5-year groups, and seasonal variation, which was analyzed by fitting a short Fourier series to the monthly birth data. RESULTS: The odds for having been born during the winter-spring months were slightly higher among both siblings and patients in all birth-year groups. However, patients born from 1955 to 1959 showed prominent seasonal variation of births, but the magnitude of this variation remained unchanged among siblings. CONCLUSIONS: Seasonal variation of births among patients with schizophrenia may consist of two factors: 1) parental procreational habits causing a slight excess of births of both patients and unaffected siblings during the winter-spring months and 2) irregular environmental factors that considerably increase the magnitude of the seasonal variation of births among patients but not their siblings.
A Phase I Study of a New Nucleoside Analogue, OSI-7836, Using Two Administration Schedules in Patients with Advanced Solid Malignancies
Authors: Chooi P. Lee, Maja J.A. de Jonge, Anne E. O'Donnell, Kristel L. Schothorst, Janet Hanwell, Jon B. Chick, Rik A. Brooimans, Laurel M. Adams, Daniel W. Drolet, Johann S. de Bono, Stan B. Kaye, Ian R. Judson, Jaap Verweij
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To investigate the safety, tolerability, and pharmacokinetic profile of the novel nucleoside analogue OSI-7836 in patients with advanced solid malignancies. Experimental Design: OSI-7836 was initially given as a 60-minute i.v. infusion on day 1 every 21 days. In view of its dose-limiting toxicities, the administration time was amended to a 5-minute bolus, and subsequently, the schedule was amended to weekly for 4 weeks followed by a 2-week rest. Blood and urine samples were collected for pharmacokinetic studies. Analyses of cytokines and lymphocyte subsets were added later in the study to elucidate a mechanism for the severe fatigue and lymphocyte depletion observed in earlier patients. Results: Thirty patients received a total of 61 treatment cycles. Fatigue was the main dose-limiting toxicity. Maximum-tolerated dose was defined as 300 mg/m2 in the 60-minute infusion, (three times per week) schedule; 400 mg/m2 in the 5-minute bolus infusion, (three times per week) schedule; and 100 mg/m2 in the weekly schedule. Other common toxicities were nausea, vomiting, rash, fever, and a flu-like syndrome. There were no clinically significant hematologic toxicities. Following the initial dose, OSI-7836 was eliminated from plasma with a median (range) elimination half-life of 48.3 minutes (22.6-64.8 minutes). Lymphocyte subset analysis showed a significant drop in B cell counts, which persisted to day 14 and beyond. Cytokine analysis showed significant elevations of interleukin-6 and interleukin-10 in all patients who received ≥200 mg/m2 OSI-7836. Best response was disease stabilization in seven patients. Conclusion: OSI-7836 was associated with excessive fatigue, and despite changes in its schedule and duration of administration, we did not observe an improvement in its tolerability. Its potentially selective effect on B lymphocytes could be exploited in further studies in specific hematologic malignancies.
Research in Stevens-Johnson syndrome/toxic epidermal necrolysis (TEN): a network of specialist TEN centres is needed to undertake effective clinical studies and therapeutic trials
Authors: D. Creamer, S. Walsh
Journal: British Journal of Dermatology (2013)

ORIGINAL ARTICLE, p 1304 When a case of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) presents, a management plan must be instigated immediately. Along with discontinuation of the culprit drug, institution of optimal supportive care is mandatory. Specialist dermatology nursing, local treatment of skin and mucous membranes, fluid replacement, nutrition and analgesia are all essential to improve the chances of survival and minimize sequelae. However, dermatologists are also prompted to consider prescribing active therapy in an attempt to ‘switch off’ keratinocyte apoptosis and limit the extension of skin involvement. Over the past 15 years, intravenous immunoglobulin (IVIg) has been used to this end, and many papers have been published indicating efficacy. However, in 2012 Huang et al.1 published a systematic review and meta‐analysis of all studies using IVIg in the treatment of SJS/TEN and concluded that the evidence does not support unambiguous therapeutic benefit. In the current issue of the BJD, Lee et al.2 have presented the outcome of 64 patients with SJS/TEN treated with IVIg in one specialist centre. This is a retrospective analysis using SCORTEN (a validated severity‐of‐illness score) at presentation to predict patient mortality. All 64 patients received IVIg in combination with a standardized regimen of supportive care. Twenty of 64 patients (31%) died; the standardized mortality rate was 1·10 (95% confidence interval 0·62–1·58), indicating that, in keeping with the conclusions of Huang et al.,1 IVIg does not appear to confer a survival benefit in TEN and may in fact be harmful. In previous studies authors have argued that the benefit of IVIg is achieved using higher doses; in the study by Lee et al.2 there was no mortality difference between patients when stratified for high dosage (≥ 3 g kg−1) vs. low dosage (< 3 g kg−1). The study's conclusion was that IVIg does not produce a survival benefit in SJS/TEN. Despite the findings from the study of Lee et al., and the conclusions from the meta‐analysis by Huang et al., we suspect that many dermatologists will continue to prescribe IVIg.
Passive Smoking Induces Atherogenic Changes in Low-Density Lipoprotein
Authors: Miia Valkonen, Timo Kuusi
Journal: Circulation (1998)

Background —According to the American Heart Association, passive smoking is an important risk factor for coronary heart disease (CHD), but the mechanisms underlying this association are not fully understood. We studied the acute effect of passive smoking on the factors that influence the development of CHD: the antioxidant defense of human serum, the extent of lipid peroxidation, and the accumulation of LDL cholesterol in cultured human macrophages, the precursors of foam cells in atherosclerotic lesions. Methods and Results —Blood samples were collected during 2 ordinary working days from healthy, nonsmoking subjects (n=10) before and after (up to 5.5 hours) spending half an hour in a smoke-free area (day 1) or in a room for smokers (day 2). Passive smoking caused an acute decrease (1.5 hours after exposure) in serum ascorbic acid ( P &lt;.001) and in serum antioxidant defense ( P &lt;.001), a decreased capacity of LDL to resist oxidation ( P &lt;.01), and the appearance of increased amounts of lipid peroxidation end products in serum ( P &lt;.01). Finally, LDL isolated from subjects after passive smoking was taken up by cultured macrophages at an increased rate ( P &lt;.05). Conclusions —Exposure of nonsmoking subjects to secondhand smoke breaks down the serum antioxidant defense, leading to accelerated lipid peroxidation, LDL modification, and accumulation of LDL cholesterol in human macrophages. These data provide the pathophysiological background for the recent epidemiological evidence about the increased CHD risk among passive smokers.
Lithogenic bile in patients with ileal dysfunction
Authors: R. H. Dowling, G. D. Bell, J. White
Journal: Gut (1972)

Ileal disease or resection causes bile salt malabsorption and a reduction in the bile salt content of bile. Since cholesterol solubility requires adequate bile salt concentrations, depletion of the bile salt content of bile might, therefore, jeopardize cholesterol solubility and predispose to cholesterol gallstone formation. To study this, we examined biliary lipid composition in 10 patients with ileal dysfunction and in 25 healthy controls. Biliary lipid composition, as analysed in cholecystokinin-stimulated, bile-rich duodenal fluid, was shown to be representative of gallbladder bile and reproducible on repeat duodenal intubation. Nine of the 10 patients with ileal dysfunction had an abnormal, supersaturated bile in which the limits of cholesterol solubility were exceeded, and while nine of 25 control subjects also had an unstable bile, the mean bile composition in the ileal dysfunction group was significantly different from the control population. These studies provide a physicochemical explanation for the clinical observation that patients with ileal dysfunction have an increased incidence of gallstones.