tbuckley/cabot-search huggingface dataset:
Chemotherapy for metastatic non-small-cell bronchogenic carcinoma: EST 2575, generation V--a randomized comparison of four cisplatin-containing regimens.
Authors: J C Ruckdeschel, D M Finkelstein, B A Mason, R H Creech
Journal: Journal of Clinical Oncology (1985)

Between December 1979, and October 1981, the Eastern Cooperative Oncology Group (ECOG) compared four cisplatin-containing regimens in the treatment of patients with metastatic non-small-cell bronchogenic carcinoma (NSCBC). CBP (cyclophosphamide, bleomycin, and cisplatin) and AFP (doxorubicin, 5-fluorouracil, and cisplatin) had shown activity in generation II of this study (EST 2575). These were compared to MVP (mitomycin C, vinblastine, and cisplatin) and CAP (cyclophosphamide, doxorubicin, and cisplatin) which were reported efficacious in single institution studies. A total of 479 previously untreated patients with metastatic NSCBC (ECOG performance status 0, 1, or 2) were entered, and of these, 432 (90%) were evaluable. Although MVP resulted in a higher response rate (5 complete responses [CRs], 22 partial responses [PRs], 26% overall) than CBP (4 CRs, 18 PRs, 20% overall), AFP (0 CRs, 18 PRs, 17% overall), or CAP (1 CR, 23 PRs, 23% overall), the difference was not significant. Survival by treatment did not differ significantly. There were 45 life-threatening and six lethal complications of therapy. Although each of the above regimens offers a modest chance of inducing greater than 50% tumor shrinkage (17% to 26%, 21% overall) the effect that these responses have an overall median survival (21.6 to 23.7 weeks, 22.9 weeks overall) is unclear.
Anti-Hu antibodies in patients with small-cell lung cancer: association with complete response to therapy and improved survival.
Authors: F Graus, J Dalmou, R Reñé, M Tora, N Malats, J J Verschuuren, F Cardenal, N Viñolas, J Garcia del Muro, C Vadell, W P Mason, R Rosell, J B Posner, F X Real
Journal: Journal of Clinical Oncology (1997)

PURPOSE Anti-Hu antibodies (HuAb) recognize antigens expressed by neurons and small-cell lung cancer (SCLC). High titers of HuAb were initially reported in serum from patients with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/SN) and SCLC. Preliminary studies have indicated that some SCLC patients without PEM/SN harbor low titer of HuAb in their serum, and that the SCLC of these patients may grow more indolently. Based on these observations, we conducted a multicenter prospective study of SCLC patients without PEM/SN to determine the incidence and prognostic implications of HuAb. METHODS Serum samples were collected at diagnosis of SCLC in 196 patients without PEM/SN. HuAb were determined by immunoblot of purified recombinant HuD antigen. RESULTS HuAb were detected in 32 (16%) of the 196 patients. Of the 170 patients who received treatment for the tumor, 27 (16%) were HuAb positive. HuAb was associated with limited disease stage (59.3% v 38.6%; P = .047), complete response to therapy (55.6% v 19.6%; P &lt; .001), and longer survival (14.9 v 10.2 months; P = .018). In a logistic regression analysis, HuAb status was an independent predictor of complete response induction. The probability of achieving a complete response was more than five times higher in HuAb-positive than in HuAb-negative patients (odds ratio, 5.4; 95% confidence interval, 1.71 to 16.89; P = .004). Cox multivariate analysis indicated that HuAb status was not independently associated with survival. CONCLUSION The presence of HuAb at diagnosis of SCLC is a strong and independent predictor of complete response to treatment. This feature accounts for the association between HuAb and longer survival.
Combining rexinoids with psoralen-ultraviolet A sheds light on the management of mycosis fungoides
Authors: Z. Ahmed, V. Piguet
Journal: British Journal of Dermatology (2012)

Journal Article Combining rexinoids with psoralen–ultraviolet A sheds light on the management of mycosis fungoides Get access Z. Ahmed, Z. Ahmed Department of Dermatology and Wound Healing, Institute of Infection and Immunity, Cardiff University School of Medicine and University Hospital of Wales, Heath Park, Cardiff, U.K. E‐mail: piguetv@cardiff.ac.uk Search for other works by this author on: Oxford Academic Google Scholar V. Piguet V. Piguet Department of Dermatology and Wound Healing, Institute of Infection and Immunity, Cardiff University School of Medicine and University Hospital of Wales, Heath Park, Cardiff, U.K. E‐mail: piguetv@cardiff.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 167, Issue 3, 1 September 2012, Page 467, https://doi.org/10.1111/j.1365-2133.2012.11192.x Published: 01 September 2012
Parent administered questionnaire captures presence and severity of doctor confirmed wheeze in infants
Authors: Marc P. van der Schee, Simone Hashimoto, Eric Haarman, Aline B. Sprikkelman, Gerben ter Riet, Wim M.C. van Aalderen, Peter J. Sterk
Journal: European Respiratory Journal (2011)

Rationale:  - Infants with confirmed wheeze are at increased risk of developing asthma. Confirmation by parents is however notoriously unreliable. We aimed to combine parent reported symptoms into a diagnostic index for the presence and severity of doctor confirmed wheeze in infants.   Methods:  -This study is part of the EUROPA-study, aimed at early prediction of asthma. Parents of 78 children (age 18±4 mo) planning to consult the family doctor for acute wheezing or dyspnea scored 11 symptoms and their severity on a scale of 0 (absent) to 5 (threatening). During home visits lung sounds were recorded for confirmation by 5 pediatric pulmonologists. Wheeze severity was simultaneously scored by validated Pediatric Respiratory Assessment Measure (PRAM) (Basco;08). Presence and severity of wheeze was modelled using backwards log-linear regression combined with ROC-analysis and linear regression, respectively.   Results:  - Parents established presence of wheeze correctly in 51% of the cases (AUC 0.50). A model combining nasal obstruction (p = 0.067), shortness of breath (p = 0.001), activity limitation (p = 0.047) and presence of fever (p = 0.06) established presence of confirmed wheeze significantly better (AUC 0.80; p    Conclusion:  - Accurate assessment of the presence and severity of wheezing in infants can be achieved by combining parent reported symptoms into a diagnostic model. Utilizing such an index is considerably more reliable than parent reported wheeze, and may help to guide treatment decisions and correctly phenotype subjects in research on the development of asthma.
Increased Striatal Dopamine Transmission in Schizophrenia: Confirmation in a Second Cohort
Authors: Anissa Abi-Dargham, Roberto Gil, John Krystal, Ronald M. Baldwin, John P. Seibyl, Malcom Bowers, Christopher H. van Dyck, Dennis S. Charney, Robert B. Innis, Marc Laruelle
Journal: American Journal of Psychiatry (1998)

The authors previously observed an increase in striatal dopamine transmission following amphetamine challenge in 15 untreated patients with schizophrenia compared to 15 matched healthy subjects. The purpose of this study was to replicate this finding in a new cohort of schizophrenic patients and healthy subjects.Fifteen patients with schizophrenia and 15 healthy subjects matched for age, gender, ethnicity, and parental socioeconomic status were recruited for this study. Patients fulfilled DSM-IV criteria for schizophrenia, had no history of alcohol or substance abuse or dependence, and were neuroleptic free for a minimum of 21 days. Amphetamine-induced dopamine release was assessed by the reduction in dopamine D2 receptor availability induced by an acute amphetamine challenge (0.3 mg/kg, intravenous bolus). Reduction in D2 receptor availability was measured with single photon emission computed tomography and the D2 receptor radiotracer [123I]IBZM.No differences were observed between patients with schizophrenia and the comparison group in D2 receptor availability at baseline. Patients with schizophrenia exhibited a significantly larger reduction in D2 receptor availability following acute amphetamine challenge than the comparison group. In this study, the effect size was smaller than in the first study. Excess dopamine release following amphetamine was associated with transient emergence or worsening of positive symptoms.In this new cohort of subjects the authors replicated their initial observation of a dysregulation of striatal dopamine release in schizophrenia.
An overview of Internet biosurveillance
Authors: D.M. Hartley, N.P. Nelson, R.R. Arthur, P. Barboza, N. Collier, N. Lightfoot, J.P. Linge, E. van der Goot, A. Mawudeku, L.C. Madoff, L. Vaillant, R. Walters, R. Yangarber, J. Mantero, C.D. Corley, J.S. Brownstein
Journal: Clinical Microbiology and Infection (2013)
100% Complete response rate in patients with cutaneous metastatic melanoma treated with intralesional interleukin (IL)-2, imiquimod, and topical retinoid combination therapy: Results of a case series
Authors: Vivian Y. Shi, Khiem Tran, Forum Patel, Jonathan Leventhal, Thomas Konia, Maxwell A. Fung, Reason Wilken, Miki Shirakawa Garcia, Sarah D. Fitzmaurice, Jayne Joo, Arta M. Monjazeb, Barbara A. Burrall, Brett King, Steve Martinez, Scott D. Christensen, Emanual Maverakis
Journal: Journal of the American Academy of Dermatology (2015)

Patients with cutaneous melanoma metastases have experienced excellent responses to intralesional interleukin (IL)-2. This has led to its recent inclusion into the US National Comprehensive Cancer Network guidelines for management of cutaneous melanoma metastases. Despite this, intralesional IL-2 has not been highlighted in the US literature nor have US physicians adopted it.We sought to evaluate the effectiveness of intralesional IL-2 combined with topical imiquimod and retinoid for treatment of cutaneous metastatic melanoma.A retrospective case series of 11 patients with cutaneous metastatic melanoma were treated with intralesional IL-2 combined with topical imiquimod and retinoid.A 100% complete local response rate with long-term follow-up (average of 24 months) was seen in all 11 patients treated with this proposed regimen. Biopsy specimens of treated sites confirmed absence of malignant cells. The most common treatment-related adverse event was rigors.Small number of patients, retrospective review of charts, and lack of a comparison group were limitations.Intralesional IL-2 administered concomitantly with topical imiquimod and a retinoid cream is a promising therapeutic option for managing cutaneous melanoma metastases. The regimen was well tolerated and should be considered as a reasonable alternative to surgical excision.
Activation of TLR3 augments the production of MMPs in human lung fibroblasts via iuducible NOS dependent pathway
Authors: Tomohiro Ichikawa, Hisatoshi Sugiura, Akira Koarai, Takashi Kikuchi, Masakazu Ichinose
Journal: European Respiratory Journal (2013)

Background : Viral infections cause exacerbations of airway diseases such as asthma and chronic obstructive pulmonary disease. Nitric oxide (NO) is excessively produced in the airways of these diseases via inducible NO synthetase (iNOS) expression. Matrix metalloproteinases (MMPs) are involved in airway remodeling and contribute to the progression of pulmonary diseases. However, the effects of viral infection on the production of iNOS and MMPs are unknown.   Aims : We examined in vitro the effects of polyinosinic-polycytidylic acid (poly I:C), an analog of viral RNA and a ligand for toll-like receptor (TLR)3, on the production of iNOS and MMPs in human lung fibroblasts, and on the signal transduction.   Methods : The productions of MMP-1, 2, 9 and iNOS were measured by zymography or western blotting after the cells were treated with poly I:C. The translocation of nuclear factor (NF)-κB p65 and interferon regulatory transcription factor (IRF)-3 into the nucleus were examined after the treatment. We also investigated the effects of N6-(1-iminoethyl)-lysine, hydrochloride (L-NIL), an iNOS inhibitor, caffeic acid phenethyl ester (CAPE), which is an NF-κB inhibitor, and knockdown of IRF-3 on poly I:C-mediated MMPs production.   Results : Poly I:C augmented the production of MMP-1, 2, 9, and iNOS expression in fibroblasts. L-NIL reduced the poly I:C-augmented production of MMPs. The translocation of NF-κB p65 and IRF-3 into the nucleus was induced by poly I:C. CAPE and knockdown of IRF-3 suppressed the poly I:C-augmented production of MMPs and iNOS.   Conclusions : The activation of TLR3 induced iNOS and, subsequently, MMPs production via both NF-κB and IRF-3 signaling in lung fibroblasts.
Primary asthma prevention amongst children — A cost-effectiveness analysis in a decision-analytic framework
Authors: G. Feljandro Ramos, Sandra Kuiper, Antoinette D.I. van Asselt, Edward Dompeling, Tanja Maas, Johan L. Severens, J. André Knottnerus, Onno C.P. van Schayck
Journal: European Respiratory Journal (2012)

Background:  Primary (prenatally-started) asthma prevention may be unifaceted or multifaceted when one or more allergen-avoidance measures are used, respectively. Presently, no study has directly compared these two categories of prevention to usual care (UC) in a trial or economic evaluation.   Aim:  To model the cost-effectiveness of prenatally-started unifaceted (UF) and multifaceted asthma (MF) primary prevention programmes with UC in a decision-analytic framework.   Methods:  A decision-tree model was developed to compare (from a healthcare perspective) two UFs and three MFs programmes to UC (unstructured allergen-avoidance advice in the Netherlands). Analyses had a time horizon of 10 years. Costs and effects for each option were evaluated through incremental cost-effectiveness ratios (ICERs).   Results:  UC and an MF were found to dominate the other options. UC turned out to be less effective but also less costly compared to the MF. To avoid one asthma case the costs will be €8,250 when choosing the MF over UC. Most of the uncertainty in the results was attributable to the cost estimates for low-risk children.  Conclusion:  Although there is no point of reference for the amount society would be willing to pay to avoid a case of asthma, the threshold used for a QALY roughly ranges between € 20,000 and € 80,000. As a case of asthma prevented will certainly equal at least one QALY gained, this study gives support to the feasibility of multifaceted programmes as viable option to replace usual care in the primary prevention of asthma amongst children.
Clinical evaluation of IP-10 and MIG including IGRAs (QFT and T-SPOT) for the diagnosis of tuberculosis infection
Authors: Yoshihiro Kobashi, Masaki Ikeda, Keiji Mouri, Shigeki Kato, Mikio Oka
Journal: European Respiratory Journal (2014)

[Objective] We focused on some chemokines related to IFN-gamma (IP-10 and MIG), and compared their usefulness for the diagnosis of TB infectionwith previous IGRAs (QFT and T-SPOT).  [Materials and Methods] The subjects consisted of 33 cases with TB diseases (definite cases), 40 cases with pulmonary nontuberculous mycobacterial (NTM) disease, and 11 cases with other respiratory diseases. We measured two IGRAs and IP-10 and MIG using the supernatant stimulated by QFT antigens in all cases, and compared the usefulness of IGRAs, IP-10, and MIG.  [Results] In the patient group of definite TB diseases, the positive response rate of QFT was 79%, that of T-SPOT was 88%, and that of IP-10 was 88%. Although there were significant differences among these diagnostic methods, they all yielded highly positive reposnse rates. In the patient group with pulmonary NTM disease including pulmonary M.kansasii, the positive response rate of QFT was 12%, that of T-SPOT.TB was 15%, and that if IP-10 was 13%. There were no significant differences among these diagnostic methods. In the patient group with other respiratory diseases, QFT showed a positive response in two cases, and IP-10 showed a positive response in 1 case. Concerning MIG, the patient group with definite TB diseases demonstrated significantly higher values than those with pulmonary NTM diseases and other respiratory diseases.  [Conclusions] Although we estimated the clinical usefulness of IP-10 and MIG to diagnose TB infection, they showed similar positive response rates. Therefore, the combination of these diagnostic methods may increase the diagnostic rate based on this study.
Dose-dependent interleukin-3 stimulation of thrombopoiesis and neutropoiesis in patients with small-cell lung carcinoma before and following chemotherapy: a placebo-controlled randomized phase Ib study.
Authors: V D'Hondt, P Weynants, Y Humblet, T Guillaume, J L Canon, M Beauduin, P Duprez, J Longueville, R Müll, C Chatelain
Journal: Journal of Clinical Oncology (1993)

PURPOSE To evaluate the safety, tolerance, and hematologic effects of recombinant human interleukin-3 (IL-3) in patients with small-cell lung cancer (SCLC) before and following multiagent antineoplastic therapy in a placebo-controlled, randomized, double-blind study. PATIENTS AND METHODS Twenty-eight patients (22 men and six women; median age, 60 years) with previously untreated SCLC entered the study. Patients were assigned to six groups of escalating-dose IL-3 ranging from 0.25 to 10 micrograms/kg/d administered by continuous infusion for 7 days, with one patient in each group receiving placebo. After a 1-week interval, the first of three cycles of carboplatin, etoposide (VP16), and epirubicin (CVE) given every 3 weeks was administered. The second cycle of CVE was followed by 7 days of IL-3 administered at the same daily dose as administered during the first infusion. RESULTS The maximum-tolerated dose was not encountered in this study. Fever was the most frequently observed side effect. Before any chemotherapy, World Health Organization (WHO) grade II fever only appeared at doses &gt; or = 2.5 micrograms/kg/d. Other side effects included rash, headache, and myalgia. During the first infusion of IL-3, before administration of chemotherapy, dose-dependent increases in peripheral-platelet counts (r = .613; P &lt; .001) and neutrophil counts (r = .505; P = .007) were observed. Following the second cycle of CVE, recovery of peripheral platelet counts was faster as compared with the first cycle of CVE for patients treated with 7.5 and 10 micrograms/kg of IL-3 (P = .021). Chemotherapy postponements due to myelotoxicity were also less frequent following the second cycle of CVE as compared with the first for patients treated with &gt; or = 2.5 micrograms/kg of IL-3 (P = .036). Compared with an age-matched historical group receiving identical chemotherapy (n = 191), administration of IL-3 did not modify either disease-free survival or overall patient survival rates. CONCLUSION IL-3 is well tolerated at doses up to 10 micrograms/kg/d. In the absence of chemotherapy, biologic effects on both neutrophils and platelets were seen at doses &gt; or = 2.5 micrograms/kg/d. IL-3 infusion following the second cycle of CVE appears to reduce chemotherapy-induced myelosuppression, but does not alter tumor response or patient survival rates.
Polymorphism at 19q13.41 Predicts Breast Cancer Survival Specifically after Endocrine Therapy
Authors: Sofia Khan, Rainer Fagerholm, Sajjad Rafiq, William Tapper, Kristiina Aittomäki, Jianjun Liu, Carl Blomqvist, Diana Eccles, Heli Nevanlinna
Journal: Clinical Cancer Research (2015)

Although most patients with estrogen receptor (ER)-positive breast cancer benefit from endocrine therapies, a significant proportion do not. Our aim was to identify inherited genetic variations that might predict survival among patients receiving adjuvant endocrine therapies.
Inhalation of activated recombinant factor VII to treat pulmonary hemorrhage in a patient with cystic fibrosis
Authors: Constantin Marcu, Robert Bals, Andreas Groeschel, Christian Lensch, Julia Woerner, Sebastian Faendrich
Journal: European Respiratory Journal (2011)

Case:  The patient (30y.o., female) was diagnosed with cystic fibrosis as child. Currently, she was hospitalized with fever and bilateral pulmonary infiltrates. She rapidly deteriorated to respiratory failure with the need of extracorporale membrane oxygenation (ECMO).  Diffus pulmonary haemorrhage complicated the course on ECMO. After 2 days of unremitting bleeding with respiratory failure we used rFVIIa as an intervention of last resort. The patient was treated with inhalation of 50 μg/kg rFVIIa in 5 ml of sodium chloride via a jet-driven nebulizer, which was repeated after 24 hours. Hemorrhage was visualized bronchoscopically, and its resolution following the treatment was immediate and did not occur again.   Discussion:  Factor VII initiates clot formation by its interaction with TF. The FVIIa-TF complex activates factor X. Activated factor X activates prothrombin to thrombin, which converts fibrinogen to fibrin. Tissue factor is expressed in the lung alveoli during inflammation and therefore pulmonary administration of human recombinant activated factor VIIa (rFVIIa) could be a rational treatment option.  Our report indicates the applicability of topical rFVIIa to control unremitting pulmonary haemorrhage. By limiting inhalation to the target organ, the therapeutic effect could be superior as a result of higher topical concentrations without systemic exposure. This could also reduce the risk of thrombotic complications reported with systemic administration of rFVIIa as well as clotting in the ECMO membrane.   Conclusion:  Intrapulmonary administration of activated recombinant factor VII (rFVIIa) via a jet-driven nebulizer may be an option in pulmonary haemorrhage.
Dynamics of QT interval from rest to peak exercise among COPD patients
Authors: Russell Franks, Afrodit Boutou, Divya Mohan, Lilian Mantziari, Tom Wong, Nicholas Hopkinson, Michael Polkey
Journal: European Respiratory Journal (2014)

Background 

Cardiovascular involvement is frequent in Chronic Obstructive Pulmonary Disease (COPD), with autonomic dysfunction a recognized feature. However, the dynamics of QT interval, a known marker of autonomic dysfunction, from rest to peak exercise in COPD patients has not yet been investigated.

Aim 

To examine the changes in QT and heart-rate corrected QT (QTc) intervals from rest to peak exercise in a population of stable COPD outpatients and of healthy controls.

Methods 

Prospectively collected data on COPD patients and healthy controls who underwent spirometry and maximum cardiopulmonary exercise testing with a continuous 12-lead ECG recording, were retrospectively analyzed. Distribution of variables was assessed with Shapiro-Wilk test and group comparisons were conducted utilizing the paired samples T-test or Wilcoxon rank test, as appropriate. Level of p<0.05 was considered significant.

Results 

The study population consisted of 143 patients (63.6% male; 62.8±7.4 years old; FEV1%=32.3±14) and 18 age and gender-matched controls. Among controls, the QT interval shortened (361.1±39.1 vs 270±27.7, p<0.001), while QTc increased (396.4±24.4 vs. 422.7±32.9, p<0.001) from rest to peak exercise. Among COPD patients, QTc interval did not increase (406.2±25.8 vs 411.9±34.2, p=0.53). QT interval shortened (333.4±34.7 vs. 299±32, p<0.001), but its absolute change was smaller, when compared to controls. Medications known to prolong QT interval did not impact on QT dynamics.

Conclusion 

COPD patients demonstrate a different exercise response; QTc interval does not increase, and QT shortening is about 30% of that seen in healthy controls.