tbuckley/cabot-search huggingface dataset:
Suicide Attempts, Gender, and Sexual Abuse: Data From the 2000 British Psychiatric Morbidity Survey
Authors: Paul E. Bebbington, Claudia Cooper, Sarah Minot, Traolach S. Brugha, Rachel Jenkins, Howard Meltzer, Michael Dennis
Journal: American Journal of Psychiatry (2009)

The purpose of this study was to utilize data from the 2000 British National Survey of Psychiatric Morbidity, a randomized cross-sectional survey of the British population that included questions relating to the phenomena of suicidality and sexual abuse, to test the hypothesis that suicide attempts in women are significantly associated with a history of sexual abuse.Participants were male and female volunteers, ages 16 to 74 years old (N=8,580), interviewed in the 2000 British National Survey of Psychiatric Morbidity.Sexual abuse was strongly associated with a history of suicide attempts as well as of suicidal intent and was more common in women. The population attributable risk fraction was considerably greater in female respondents (28%) than in male respondents (7%), which is consistent with more prevalent exposure to sexual abuse among women. The effect of sexual abuse on suicidal attempts and suicidal intent was reduced by controlling for affective symptoms, suggesting that the effect of the former was likely to be mediated by affective changes.Sexual abuse is a significant antecedent of suicidal behavior, particularly among women. In identifying suicidal behavior, it is important to consider the possibility of sexual abuse, since it implies a need for focused treatment.
Carcinogenic Activity of Petasitenine, a New Pyrrolizidine Alkaloid Isolated From Petasites japonicus Maxim2
Authors: Iwao Hirono, Hideki Mori, Kiyoyuki Yamada, Yoshimasa Hirata, Masanobu Haga, Hiroshi Tatematsu, Shigeki Kanie
Journal: JNCI Journal of the National Cancer Institute (1977)

The carcinogenic activity of petasitenine, a new pyrrolizidine alkaloid isolated from young flower stalk of Petasites japonicus, was studied in ACI rats. All rats that had received a 0.05% solution of petasitenine in drinking water died or were killed in moribund condition 72 days after the start of experiment. They showed necrosis, hemorrhage, and remarkable proliferation of the bile ducts in the liver. In another group that had received a 0.01% solution, 8 of 10 animals surviving beyond 160 days developed tumors in the liver, i.e., hemangioendothelial sarcomas in 5 rats and liver cell adenomas in 5 rats, 2 of which simultaneously developed hemangioendothelial sarcomas. No tumors were observed in the livers of the control animals.
Peripheral mononuclear cell response to nonspecific antigenic stimulation in children with obese asthma phenotype
Authors: Hasan Yuksel, Ozge Yilmaz, Seda Vatansever, Ece Onur, Cengiz Kirmaz, Emine Nal, Ahmet Turkeli, Ferda Bozyigit
Journal: European Respiratory Journal (2012)

Background: Investigation of immunopathogenetic mechanisms of obesity associated asthma may demonstrate novel therapeutic targets.  Objective: The aim of this study was to compare levels of Th1, Th2, Treg and Th17 cytokines secreted by peripheral mononuclear cell culture (PBMC) in response to nonspecific stimulation in obese and nonobese children with asthma.  Methods: Obese and nonobese children with asthma aged 5 to 16 were enrolled into this case-control study consecutively. Age at asthma diagnosis and clinical severity were recorded. Skin prick test was performed. Serum adipokine levels as well as PBMC supernatant IL-4, IL-10, IL-17, IL-23, IFNγ and TGF-β levels were measured.  Results: Mean (± standard deviation) ages of obese (n=28) and nonobese (n=39) children with asthma were 8.7 ± 2.9 and 10.5 ± 3.2 respectively. Asthma symptom score was higher and age at asthma diagnosis was lower in obese compared to nonobese children with asthma (p=0.03 and p=0.004 respectively). Leptin levels were significantly higher in obese than nonobese asthma group (p  Conclusion: Low IL-10 and high TGF-β levels in obese compared to nonobese children with asthma might indicate lower antiinflammatory cytokine secretion and regulatory T lymphocyte function as well as a higher remodelling process in obesity associated asthma in children.
Treatment of advanced-stage Hodgkin's disease: alternating noncrossresistant MOPP/CABS is not superior to MOPP.
Authors: D L Longo, P L Duffey, V T DeVita, P H Wiernik, S M Hubbard, J C Phares, A W Bastian, E S Jaffe, R C Young
Journal: Journal of Clinical Oncology (1991)

One hundred twenty-five assessable patients with advanced-stage Hodgkin's disease were randomized to receive mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or MOPP alternating with lomustine (CCNU), doxorubicin, bleomycin, and streptozocin (CABS). The median follow-up is 7.7 years. The complete response rate was 60 of 66 MOPP-treated patients (91%) and 54 of 59 MOPP/CABS-treated patients (92%) (difference not significant). The level of the disease-free survival curve at longest follow-up is 65% for MOPP-treated patients and 72% for MOPP/CABS-treated patients (difference not significant). The overall survival at 12 years is projected at 68% for MOPP-treated patients and 54% for MOPP/CABS-treated patients (difference not significant). Thus, there were no significant differences in efficacy between MOPP and MOPP/CABS. However, MOPP/CABS was more emetogenic than MOPP, and four MOPP/CABS-treated patients went on to develop secondary acute leukemia. No MOPP-treated patients developed leukemia. High initial erythrocyte sedimentation rate (ESR) and high platelet counts adversely affected treatment outcome. MOPP-treated patients who received greater than 81% of the projected dose intensity of vincristine over the first three cycles had significantly improved disease-free survival rates over those receiving less than 81%. MOPP/CABS-treated patients who received greater than 82% of the projected dose intensity of vincristine had significantly better overall survival than those who received less than 82%. Disease-free survival on both arms was significantly better in patients who received greater than 84% of the projected dose intensity of all agents. The effect of dose intensity was particularly apparent in patients with poor prognostic factors where those who received greater than 84% of the projected dose intensity of all agents had significantly improved disease-free and overall survival.
European Union of Medical Specialists (UEMS): Section of Rheumatology, and European Board of Rheumatology (EBR)
Authors: A D Woolf
Journal: Annals of the Rheumatic Diseases (2003)

The aim of the UEMS Section of Rheumatology/European Board of Rheumatology is to maintain the highest level of care with the best outcome for those with musculoskeletal conditions through establishing and maintaining high professional standards amongst rheumatologists in Europe.
Adult-onset asthma: Risk factors
Authors: Teresa Gomez Garcia, Javier De Miguel Díez, Roberto Pelta Fernández, MªCarmen Juarez Morales, Liliana Moran Caicedo, Veronica Sanz de Burgoa, Julio Hernandez Fernandez
Journal: European Respiratory Journal (2011)

To determine the risk factors for the development of asthma in patients older than 12 years.   Methods:  An observational, transversal, multicentric, case-control study was led from May to October 2009 in Spain. Patients over 12 years old, diagnosed of asthma in the last 12 months that went to a neumologist or allergist clinic for any reason were chosen as cases. Each case had at least a non-asthmatic control chosen in the first 7 days after inclusion. Bivariate and multivariate analysis was made.   Results:  After exclusion criteria, 247 cases and 671 controls were included in the study. Mean age was 28.3±8.2, 54.9% women. No significant differences were found by BMI (p=0.4965) or smoking habits (p=0,1327). Age was a protective factor (OR 0.969; CI95% 0.948-0.991), and so was educational level (OR 0.685; CI95% 0.546-0.856). Other risk factors were animals hypersensitivity (OR 2.581; CI95% 1.515-4.399), other allergens hypersensitivity (OR 1.984; CI95% 1.306-3.015), rhinitis (OR 1.878; CI95% 1.263-2.794), exposure to irritant substances (OR 1.733; CI95% 1.075-2.793), NSAID hypersensitivity/intolerance (OR 2.305; CI95% 1.066-4.983) and familiar history of asthma (OR 1.543; CI95% 1.073-2.220).   Conclusions:  This study demonstrates that higher age and superior educational level behave as protective factors, while animals hypersensitivity, other allergens hypersensitivity, rhinitis, exposure to irritant substances, NSAID hypersensitivity/intolerance and familiar history of asthma were risk factors for the development of adult-onset asthma. Further studies should be made in order to prevent this disease.
Physical activity promotes pulmonary recovery after cardiac surgery
Authors: Marcus Jonsson, Elisabeth Westerdahl
Journal: European Respiratory Journal (2012)

Introduction   It is well known that physical activity has substantial impact on general health and mortality. Benefits of physical activity have been reported for patients after cardiac surgery. Patients undergoing cardiac surgery have reduced lung function postoperatively and often suffer from postoperative pulmonary complications.  No studies have been published where the relationship between physical activity and lung function after cardiac surgery has been investigated.   Aim   To test the hypothesis that physical activity is positively correlated with pulmonary recovery, the relationship between postoperative self-reported physical activity and lung function, two months after cardiac surgery, was investigated.   Methods   In a prospective cohort study, a sample of 76 patients undergoing cardiac surgery between 2007 and 2009, was followed up two months after cardiac surgery. Physical activity level was quantified using a categorical question on physical activity at work and during leisure time. Lung function was measured by spirometry. The measurements were made preoperatively and 2 months postoperatively.   Result   Two months postoperatively the patients had increased their self-reported level of physical activity. Patients with a higher level of physical activity showed a significantly better recovery of lung function two months after cardiac surgery (VC 95 % ± 11 vs 91 % ± 7 (p = 0,043) and FEV1 93 % ± 8 vs 89 % ± 6 (p = 0,008)) compared to patients reporting low physical activity.   Conclusion   A higher level of physical activity, during the first two months after cardiac surgery is associated with a better recovery of lung function, compared to being less active or sedentary.
Phase I trial of doxorubicin with cyclosporine as a modulator of multidrug resistance.
Authors: N L Bartlett, B L Lum, G A Fisher, N A Brophy, M N Ehsan, J Halsey, B I Sikic
Journal: Journal of Clinical Oncology (1994)

PURPOSE To study the effects of cyclosporine (CsA), a modulator of multidrug resistance (MDR), on the pharmacokinetics and toxicities of doxorubicin. PATIENTS AND METHODS Nineteen patients with incurable malignancies entered this phase I trial. Initially patients received doxorubicin alone (60 or 75 mg/m2) as a 48-hour continuous intravenous (i.v.) infusion. Patients whose tumors did not respond received CsA as a 2-hour loading dose of 6 mg/kg and a 48-hour continuous infusion of 18 mg/kg/d with doxorubicin. Target CsA levels were 3,000 to 4,800 ng/mL (2.5 to 4.0 mumol/L). Doxorubicin doses were reduced to 40% of the prior dose without CsA, and then escalated until myelosuppression equivalent to that resulting from doxorubicin alone was observed. Doxorubicin pharmacokinetics were analyzed with and without CsA. RESULTS Thirteen patients received both doxorubicin alone and the combination of doxorubicin and CsA. Mean CsA levels were more than 2,000 ng/mL for all cycles and more than 3,000 ng/mL for 68% of cycles. Dose escalation of doxorubicin with CsA was stopped at 60% of the doxorubicin alone dose, as four of five patients at this dose level had WBC nadirs equivalent to those seen with doxorubicin alone. Nonhematologic toxicities were mild. Reversible hyperbilirubinemia occurred in 68% of doxorubicin/CsA courses. The addition of CsA to doxorubicin increased grade 1 and 2 nausea (87% v 47%) and vomiting (50% v 10%) compared with doxorubicin alone. There was no significant nephrotoxicity. Paired pharmacokinetics were studied in 12 patients. The addition of CsA increased the dose-adjusted area under the curve (AUC) of doxorubicin by 55%, and of its metabolite doxorubicinol by 350%. CONCLUSION CsA inhibits the clearance of both doxorubicin and doxorubicinol. Equivalent myelosuppression was observed when the dose of doxorubicin with CsA was 60% of the dose of doxorubicin without CsA. Understanding these pharmacokinetic interactions is essential for the design and interpretation of clinical trials of MDR modulation, and should be studied with more potent MDR modulators.
Emperipolesis in a patient receiving romiplostim
Authors: Nichola Cooper, Barbara J. Bain
Journal: American Journal of Hematology (2015)

A 22-year-old man with autoimmune thrombocytopenic purpura that was refractory to high-dose corticosteroids and high-dose intravenous immunoglobulin was prescribed romiplostim, a thrombopoietin mimic, in an increasing dose to a maximum of 10 μg/kg. There was no response of the platelet count, which did not rise above 11 × 109/l. However, a subsequent bone marrow aspirate showed abundant megakaryocytes with prominent emperipolesis (images). Emperipolesis is the active entry of a living cell into another. In the hemopoietic system, it is most often observed as the entry of other cells—granulocytes, erythroblasts, lymphocytes—into the surface-connected canalicular system of megakaryocytes. It differs from phagocytosis in that the cell that penetrates another cell remains intact and is cytologically normal. The term is derived from the Greek em inside, peri around, polemai to wander about; it was coined by Humble et al. to describe the behavior or lymphocytes in relation to megakaryocytes, malignant cells, and hemopoietic cells in mitosis 1. Emperipolesis is a common observation if a large number of megakaryocytes are examined and does not seem to have any specific diagnostic significance 2. It can occur both with neoplastic and with normal megakaryocytes. It is rarely as prominent as in the current patient.
Unique two-cell co-culture assays show mutual dependence of macrophages and breast cancer cells in invasion
Authors: Sumanta Goswami, Erik A. Sahai, Jeffrey B. Wyckoff, Dianne Cox, Fiona J. Pixley, John S. Condeelis
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

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One of the key steps in the metastatic spread of tumors is the invasion of tumor cells into the surrounding connective tissue and blood vessels. The presence of increasing numbers of macrophages in primary tumors has been shown to correlate with poor prognosis. The possible mechanism supporting this observation was not available until recently, when a paracrine loop was proposed between the tumor cells and the macrophages mediated by the growth factors Epidermal growth factor (EGF) and Colony stimulating factor-1 (CSF-1). EGF was shown to be synthesized by macrophages and CSF1 by carcinoma cells in tumors exhibiting the paracrine interaction between these cell types. In order to further elucidate the paracrine loop we have reconstituted the paracrine loop in vitro. In a 2D assay, carcinoma cells (MTLn3) and macrophages (BAC) were co-cultured on glass and they exhibit polarization towards each other when stimulated with CSF-1. The effect is dependent on the activation of EGF receptors as evident by the absence polarization in the presence of EGFR blocking drugs. The mechanism of this polarization is being studied. In a 3D assay, these cells are co-cultured on glass and allowed to invade an overlaid collagen matrix. In this assay, optimum invasion occurs only in the presence of both cell types and requires CSF1, and EGF-R function. RTPCR demonstrates the expression of EGFR and CSF-1 message in the carcinoma cells and EGF and Colony stimulating factor-1 receptor message in the macrophages. Taken together these results along with the evidence published before by our group, indicate that the carcinoma cells and macrophages interact closely in a paracrine loop augmenting invasion and possibly intravasation and metastasis.
Prognostic value of self-reported fatigue on overall survival in patients with myelodysplastic syndromes: a multicentre, prospective, observational, cohort study
Authors: Fabio Efficace, Gianluca Gaidano, Massimo Breccia, Maria Teresa Voso, Francesco Cottone, Emanuele Angelucci, Giovanni Caocci, Reinhard Stauder, Dominik Selleslag, Mirjam Sprangers, Uwe Platzbecker, Alessandra Ricco, Grazia Sanpaolo, Odile Beyne-Rauzy, Francesco Buccisano, Giuseppe A Palumbo, David Bowen, Khanh Nguyen, Pasquale Niscola, Marco Vignetti, Franco Mandelli
Journal: The Lancet Oncology (2015)
Increase of Rat Pulmonary Microvascular Permeability to Albumin by Recombinant Interleukin-2
Authors: Fairman Rp, Glauser Fl, Merchant Re, Bechard D, Fowler Aa
Journal: Cancer Research (1987)

Immunotherapy with the lymphokine interleukin-2 (IL-2), with or without lymphokine activated killer (LAK) cells, offers a new approach to the treatment of solid tumors. Unfortunately, most patients receiving IL-2 and LAK cells develop a “third space syndrome” from a presumed generalized increase of vascular permeability. We have investigated the role of IL-2 on lung fluid balance, by measuring changes in lung water and albumin intake. Rats were injected with IL-2 500,000 U i.p. three times a day for 1 to 4 days. At the completion of the injections, lungs were isolated and perfused, and total lung water (TLW) and 125I-albumin uptake were measured. After 1 day of injections, TLW increased from 4.90 ± 0.14 to 5.57 ± 0.34 ml/g dry lung and albumin uptake nearly doubled from 0.47 ± 0.08 to 0.91 ± 0.28 cm3/s/g dry lung × 10-3. Longer injection periods increased both TLW and albumin uptake further. After 2 days, TLW and albumin uptake were also significantly increased by 160,000 U i.p. three times a day, but not by 40,000 or 10,000 U. To eliminate possible contributions to increased permeability by ( a ) LAK cells generated in vivo , or ( b ) circulating leukocytes, we isolated lungs from normal rats and perfused them for 5 min with a cell-free perfusate containing IL-2 (2, 10, or 5 × 10-3 U/ml) excipient or 0.9% NaCl placebo. TLW was similar in all groups, but albumin uptake was significantly increased by 10,000 and 50,000 U/ml (0.94 ± 0.15 and 0.82 ± 0.16 cm3/s/g dry lung × 10-3, respectively), but not by 2,000 U/ml. We conclude that lung microvascular albumin permeability is increased following administration of IL-2 in vivo and in vitro . We suggest that LAK cells are not required for the initiation of increased permeability and that IL-2 may have some direct effect on the pulmonary microvasculature.
Acute exacerbation of idiopathic pulmonary fibrosis: shifting the paradigm
Authors: Christopher J. Ryerson, Vincent Cottin, Kevin K. Brown, Harold R. Collard
Journal: European Respiratory Journal (2015)

The goal of this review is to summarise the clinical features, management, and prognosis of acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF). AE-IPF has previously been defined based on clinical and radiological features that include the subacute onset of dyspnoea, bilateral ground glass changes on chest high-resolution computed tomography, and the absence of an identifiable aetiology. The annual incidence of AE-IPF is typically reported at 5-15%, but is less common in mild disease. Features of diffuse alveolar damage are present when a biopsy is performed. Idiopathic pulmonary fibrosis (IPF) patients with acute respiratory worsening are often initially treated with high dose corticosteroids and antimicrobials; however, there are no clear data to support these therapies, and the short-term mortality of AE-IPF is ~50%. Recent studies have shown that the features and prognosis of AE-IPF are similar to other causes of acute respiratory worsening, including infection, aspiration, air pollution and mechanical injury to the alveolar epithelium. Based on this emerging evidence, we propose a novel approach to the classification of acute respiratory worsening events in patients with IPF that focuses on clinical and radiological findings consistent with an underlying pathobiology of diffuse alveolar damage.
Non-invasive ventilation for acute respiratory failure due to exacerbation of COPD; a national survey in the Netherlands on the adherence to the Dutch guideline
Authors: Janneke Hilderink, Anna van Gemert, Folkert Brijker, Ron Vaartjes, Michiel Wagenaar
Journal: European Respiratory Journal (2014)

Objective  Non-invasive ventilation (NIV) is common practice in acute hypercapnic respiratory failure (AHRF) due to exacerbation of COPD. Nowadays, many international and national guidelines have been published. However, the generalizability of guidelines to the general practice is unclear in most countries. A national survey was performed to evaluate the adherence to the Dutch guideline (July 2013) for the use of NIV in COPD patients.   Methods  A 10-item web based questionnaire was developed in September 2013. All pulmonary physicians in the Netherlands were invited to respond. The topics of questions were: year of introduction of NIV on the pulmonary ward, awareness of the Dutch guideline, number of patients per year treated with NIV and success rates. The recommendations in the Dutch guidelines for NIV were considered to be standard care.   Results  Pulmonary physicians of 74 hospitals responded. In 40/74 (54%) hospitals NIV is available on the pulmonary ward. The year of introduction ranged from 1998-2012. In 37 hospitals (93%), doctors were aware of the Dutch NIV guideline. Guideline adherence rate was 65%. The stratified number of NIV patients per year were: 10-20: n=5 (13%), 20-50: n=14 (35%), 50-75: n=3 (8%), 75-100: n=1 (3%), unknown: n=17 (43%). Success rates were:  90%: n=10 (25%), unknown: n=17 (43%).   Conclusion  Even though there is a wide range in the number of patients treated with NIV per year and in the success rates, the national guidelines for NIV in COPD on the pulmonary ward seem to be well adopted in Dutch hospitals.
Induction of Immunity to a Mouse Lymphoma by Multiple Methods, Including Vaccination With Soluble Membrane Fractions2
Authors: Morton D. Prager, Ariel C. Hollinshead, R. J. Ribble, Ina Derr
Journal: JNCI Journal of the National Cancer Institute (1973)

6C3HED lymphoma grows to the point of lethality from a small inoculum in C3H mice, the strain of origin. Noncytotoxic antibodies that form during tumor growth give evidence of an immune response by the host. C3H mice were rendered immune to 6C3HED by 1) L-asparaginase treatment of tumorbearing animals, 2) vaccination with iodoacetamide- modified 6C3HED cells, 3) transfer of spleen and lymph node cells from immune mice (100% protection at a lymphoid cell: tumor cell ratio of 100 : 1), 4) preincubation of tumor cells with noncytotoxic immune serum before injection into nonimmune hosts, and 5) vaccination with soluble 6C3HED membrane antigen(s). Two membrane fractions isolated from Sephadex G-200 columns contained antigens that were effective in protective vaccination and in neutralizing antibody in the highly specific C3H anti-6C3HED.