tbuckley/cabot-search huggingface dataset:
Phase III Clinical Trial of the Combination of Cisplatin, Dacarbazine, and Carmustine With or Without Tamoxifen in Patients With Advanced Malignant Melanoma
Authors: Edward T. Creagan, Vera J. Suman, Robert J. Dalton, Henry C. Pitot, Harry J. Long, Michael H. Veeder, Allen M. Vukov, Kendrith M. Rowland, James E. Krook, John C. Michalak
Journal: Journal of Clinical Oncology (1999)

PURPOSE: A prospective randomized phase III clinical trial was conducted to assess whether the addition of tamoxifen (TAM) to the three-agent regimen of cisplatin (CDDP), dacarbazine (DTIC), and carmustine (BCNU) significantly increased the progression-free survival and overall survival of patients with advanced malignant melanoma. PATIENTS AND METHODS: Patients with advanced malignant melanoma were treated with CDDP + DTIC + BCNU (CDB) with or without TAM. The dose schedule was CDDP 25 mg/m 2 given intravenously (IV) for 30 to 45 minutes in 500 mL of dextrose and ½ normal saline (NS) on days 1 to 3 of a 3-week cycle; DTIC 220 mg/m 2 IV for 1 hour in 500 mL of dextrose and ½ NaCl on days 1 to 3 of a 3-week cycle; BCNU 150 mg/m 2 IV for 2 to 3 hours in 750 to1,000 mL of dextrose and 5% water onday 1 of every odd 3-week cycle; and TAM 20 mg taken orally every morning. RESULTS: There were 184 eligible patients enrolled. These patients were observed until death or for a minimum of 1.3 years. At last contact, 12 were still alive. The median time to progression was 3.4 months on the CDB arm and 3.1 months on the CDB + TAM arm. The median survival time was 6.8 months with CDB and 6.9 months with CDB + TAM. Progression-free survival (P = .429) and overall survival (P = .545) were not found to differ by treatment. CONCLUSION: The addition of TAM to this three-agent regimen of CDB was not found to provide a meaningful clinical advantage in the treatment of patients with advanced malignant melanoma.
Sixteen-week multidrug regimen versus cyclophosphamide, doxorubicin, and fluorouracil as adjuvant therapy for node-positive, receptor-negative breast cancer: an Intergroup study.
Authors: J H Fetting, R Gray, D L Fairclough, T J Smith, K A Margolin, M L Citron, M Grove-Conrad, D Cella, K Pandya, N Robert, I C Henderson, C K Osborne, M D Abeloff
Journal: Journal of Clinical Oncology (1998)

PURPOSE The Intergroup conducted this breast cancer adjuvant trial to compare an investigational 16-week regimen with cyclophosphamide, doxorubicin, and fluorouracil (5-FU; CAF). The 16-week regimen features greater doxorubicin and 5-FU dose-intensity than CAF and improved scheduling of antimetabolites with sequential methotrexate and 5-FU, as well as infusion 5-FU. PATIENTS AND METHODS A total of 646 node-positive, receptor-negative patients were randomly assigned to receive either the 1 6-week regimen or six cycles of CAF. Breast cancer outcomes included recurrence as well as disease-free and overall survival. Toxicity was evaluated by the Common Toxicity Criteria (CTC). Treatment-related quality of life was assessed by the Breast Chemotherapy Questionnaire (BCQ) before, during, and 4 months after treatment in 163 patients. The trial was designed to use one-sided tests of significance for power calculations, but is now reported with both one-sided and the traditional two-sided tests of significance. RESULTS At a median follow-up of 3.9 years, the estimated 4-year recurrence-free survival rate was 67.5% with the 16-week regimen versus 62.7% with CAF (P = .19, two-sided; P = .095, one-sided). The estimated 4-year survival rate was 78.1% with the 16-week regimen versus 71.4% with CAF (P = .10, two-sided; P = .05, one-sided). CAF produced significantly higher grades of leukopenia, granulocytopenia, and thrombocytopenia, as well as liver and cardiac toxicity, whereas the 16-week regimen produced significantly higher grades of anemia, nausea, stomatitis, and weight loss, as well as skin and neurotoxicity. There were three treatment-related deaths with CAF but none with the 16-week regimen. During treatment, quality of life declined significantly more with the 16-week regimen than CAF, but by 4 months posttreatment, there was no difference. CONCLUSION The 16-week regimen produced marginally better breast cancer outcomes than CAF with similar toxicity but a greater reduction in during-treatment quality of life. The 16-week regimen should not be used instead of a standard-dose regimen without careful consideration of the 16-week regimen's pros and cons, which include its complicated schedule. It should probably not be tested further, but its antimetabolite schedules and frequent drug administration (ie, dose density) should be considered in the development of new regimens.
Cross-Cultural Evaluation of Schneider’s First-Rank Symptoms of Schizophrenia: A Report from the International Pilot Study of Schizophrenia
Authors: WILLIAM T. CARPENTER, JOHN S. STRAUSS
Journal: American Journal of Psychiatry (1974)

The authors analyzed diagnostic data collected in nine countries in an effort to determine the clinical usefulness of Kurt Schneider's II "first-rank symptoms" (FRSs) of schizophrenia. The study specifically sought to determine whether the prevalence of FRSs in patients diagnosed as schizophrenic (N = 811) justified their use in diagnosis, what the frequency distribution was among FRSs, and whether or not FRSs were pathognomonic of schizophrenia, as Schneider claimed. The findings showed that FRSs do occur with sufficient frequency to have potential diagnostic usefulness and that each of the nine FRSs analyzed is highly discriminating for schizophrenia. However, since FRSs were also reported in patients receiving other psychiatric diagnoses. FRSs cannot be considered absolutely discriminating for schizophrenia.
Overall survival (OS) in Swedish RCC patients treated 2000–2012: Update of the RENCOMP study.
Authors: Magnus Lindskog, Thomas Wahlgren, Rickard Sandin, Jan Kowalski, Maria Jakobsson, Sven Lundstam, Börje Ljungberg, Ulrika Harmenberg
Journal: Journal of Clinical Oncology (2015)

413 Background: The RENal COMParison (RENCOMP) study showed a significant improvement in OS for Swedish patients diagnosed with renal cell carcinoma (RCC) and metastatic (m)RCC in the first years following the introduction of targeted agents (TAs) in 2006 (Br J Cancer 2013;108:1541). Here we investigated whether a further improvement in OS can be detected in the more recent years of the TA era. Methods: Using data from the Swedish Cancer Register (diagnosis and death records), National Patient Register (in-/out-patient visit records), and Swedish Prescribed Drug Register (prescribed/dispensed drug records), we assessed OS in RCC and mRCC patients diagnosed during two periods after (2009–2012 and 2006–2008) and one period before (2000–2005 [RCC]; 2002–2005 [mRCC]) the introduction of TAs, and factors influencing OS in mRCC. Multivariate analysis was performed using a Cox proportional hazards model, including estimates of adjusted HR. The regression model included the covariates age, gender, geographical region, institution size, nephrectomy status, diagnosis period, and TA prescription. Results: In total, 3,980, 2,956, and 5,225 RCC patients were identified from 2009–2012, 2006–2008, and 2000–2005, respectively. From 2002–2012, 4,217 patients met the criteria for mRCC diagnosis. RCC patients diagnosed 2009–2012 and 2006–2008 had a significant improvement in OS compared with patients diagnosed 2000–2005 (median OS: not reached and 86 vs. 48 months, respectively; both P&lt;0.001 [log-rank]). Likewise, mRCC patients diagnosed 2009–2012 and 2006–2008 had a significant improvement in OS compared with patients diagnosed 2002–2005 (median OS: 18.0 and 13.0 vs. 10.0 months, respectively; both P&lt;0.001 [log rank]; with adjusted HR [95% CI] of 0.76 [0.69–0.83] and 0.97 [0.89–1.06], respectively). Factors significantly associated with longer OS in mRCC were (HR, 95% CI): female gender (0.88, 0.82–0.94), lower age (0.97, 0.97–0.98), prior nephrectomy (0.57, 0.53–0.61), and a TA prescription (0.84, 0.77–0.91). Conclusions: A continued significant improvement in OS for RCC and mRCC patients was shown, reflecting intensified medical and surgical treatment, more available TAs, and increased clinical experience.
Are upper airways resistance syndrome and obstructive sleep apnea a side-effect of oral cancer therapy?
Authors: S Tandon, A. Khutarkar, S. Ansari, M. Khale, S. Rajan, Joyita Deodhar, J.P. Agarwal, Pankaj Chaturvedi, P. Pai, Devendra Chaukar, Rohini Havaldar, Siddhartha Laskar, Prabha Yadav, Anil D'Cruz
Journal: European Respiratory Journal (2011)

Background: Reconstructive surgery and radiotherapy cause changes in airway calibre and tone which may lead to Upper Airways Resistance Syndrome (UARS) and Obstructive Sleep Apnea (OSA). We aimed to study the prevalence of UARS and OSA in treated Oral Cancer patients.

Methodology: 78 patients (69 males, 9 females, mean age 49 years) treated for Oral Cancer were administered the Epworth Sleepiness Scale (ESS). Patients' perception of sleep quality (SLq) and mental health status were noted from Mental Health and Quality of Life Questionnaires (GHQ28, EORTC QLQ-C30 (V03), QLQ-H&N35) and all underwent Polysomnography. They were categorised on the basis of Respiratory Disturbance Index (RDI) {i.e.Apnea-Hypopnea Index (AHI) with Respiratory Effort Related Arousals (RERAs)} into Normal (RDI 15/h) and Sleep Disordered Breathing (SDB) where (SDB=UARS+OSA: RDI>5/h).

Results: 66 patients underwent surgery with adjuvant (chemo)radiation and remaining 12 (chemo)radiation.SDB defined by RDI was present in 70.5% as compared to 29.5% defined by AHI. 48.7% had UARS and 21.8% had OSA.SLq was significantly associated with high GHQ28 scores (p=0.002) and SDB (p=0.04).

Conclusions: Upper Airways Resistance Syndrome and Obstructive Sleep Apnea are a common yet unrecognised problem in treated Oral Cancer patients.Apnea-Hypopnea Index underestimated SDB,UARS and OSA significantly (29.5%,24.4% and 5.1% respectively)with a higher prevalence (70.5%,48.7% and 21.8%) as per the Respiratory Disturbance Index which included Respiratory Effort Related Arousals.Poor mental health is associated with disturbed sleep in these patients,but Sleep Disordered Breathing may also be a contributing factor.
Induction of protective T cell immunity against influenza using a novel peptide vaccine
Authors: Tom Wilkinson, Olga Pleguezuelos, Stuart Robinson, Gregory Stoloff, Rob Lambkin Williams, John Oxford, Alex Mann, Anthony Gilbert, Wilson Caparros-Wanderley
Journal: European Respiratory Journal (2012)

Influenza infection remains an important cause of global morbidity despite current vaccine strategies which generate antibody responses to surface viral proteins. Recent studies have established that naturally occurring T cells which recognise highly conserved core viral proteins and limit illness against a range of viral strains.We aimed to demonstrate that induction of T cell memory using a novel peptide vaccine (Flu-V) could limit influenza severity using a human viral challenge model.  32 seronegative healthy males were randomised to receive 500μg of peptide vaccine or placebo. All subjects were challenged by nasal instillation of live A/Wisconsin/67/2005 (H3N2). Safety, tolerability, influenza severity and cellular immunity data were collected.  The vaccine was safe and well tolerated. No pre-existing T cell responses to the novel Flu-V vaccine were seen at baseline by IFN-y release assay. All subjects in the treatment arm demonstrated strong induction of the peptide specific cellular response (fold rise 8.2± 3.9 (Range 2.0-30.6) p=0.0005). The strength of the induction of T cell response to Flu-V inversely correlated with influenza illness severity -symptoms r=-0.786, p=0.02 and viral shedding r=-0.821, p=0.01. Furthermore the peptide vaccine induced strong cellular responses against heterologous strains including H1N1pdm in vitro.  Peptide vaccination can induce cellular immunity to influenza which correlates closely with disease protection in humans. T cell responses can be induced against a range of strains and therefore this approach carries potential for the induction of broad heterologous immunity required to protect against future pandemics.
Effect of megestrol acetate on quality of life in a dose-response trial in women with advanced breast cancer. The Cancer and Leukemia Group B.
Authors: A B Kornblith, D R Hollis, E Zuckerman, A P Lyss, G P Canellos, M R Cooper, J E Herndon, C A Phillips, J Abrams, J Aisner
Journal: Journal of Clinical Oncology (1993)

PURPOSE The impact of the side effects of megestrol acetate on the quality of life of noncachectic women with advanced breast cancer was studied in a dose-response clinical trial of the Cancer and Leukemia Group B (CALGB 8741). Side effects of appetite increase and weight gain at higher doses were predicted to have a negative effect on quality of life. PATIENTS AND METHODS Stage IV breast cancer patients were randomized to receive either 160, 800, or 1,600 mg/d of megestrol acetate. Quality of life was assessed in 131 patients at trial entry and at 1 and 3 months while on treatment, by telephone interview, using the following measures: the Functional Living Index-Cancer (FLIC), Rand Functional Limitations Scale, Rand Mental Health Inventory (MHI), the Body Image Subscale, and linear analog scales of drug side effects. RESULTS At 3 months, women treated with 160 mg/d reported less severe side effects (P &lt; .0005), better physical functioning (FLS, P &lt; .0005), less psychologic distress (MHI, P = .008), and an improvement in overall quality of life (FLIC, P = .003) from the time of study entry as compared with those treated with 1,600 mg/d. Patients who received the 800-mg/d dose fell between the low- and high-dose arms in reported intensity of drug side effects, but responded similarly to those in the 160-mg/d group in terms of physical functioning, psychologic distress, and overall quality of life. CONCLUSION Unless additional follow-up data demonstrate a survival advantage at higher doses, the 160-mg/d dose is optimal, achieving maximal treatment effect with the fewest side effects and better quality of life.
Evidence for a Deficiency in Inter-Molecular Cross-Linking in Collagen Fibrils Isolated from Rheumatoid Joints
Authors: F. S. Steven
Journal: Annals of the Rheumatic Diseases (1966)

Collagen fibrils can be isolated from mature uncalcified connective tissue by a preliminary treatment with crude bacterial a-amylase.This type of collagen fibril has been described as Nishihara collagen (Steven, 1964).Amino acid analyses of Nishihara collagen preparations indicate that the fibrils are a highly purified form of collagen, containing less of the impurities which are often found in trace amounts in preparations of acid soluble collagen (Steven, in preparation).Electron microscopic examination of reconstituted acid soluble collagen fibrils and Nishihara collagen fibrils indicate that both are made up of collagen molecules (tropocollagen monomers) polymerized laterally and endto-end.Reconstituted collagen fibrils are held together by non-covalent bonds, e.g.ionic, hydrogen, and hydrophobic bonds.However, Nishihara collagen fibrils have in addition a second type of stabilizing force, covalent cross-linkages between monomers, which confer stability on the fibril towards physical and biological destruction.Nishihara collagen provides us with purified samples of naturally-occurring collagen at the fibrillar level.Nishihara collagen fibrils isolated from rheumatoid knee joints were previously demonstrated to be more susceptible to proteolytic digestion by pronase than were collagen fibrils isolated from normal synovia (Steven, 1965).Chemical studies (Steven, 1966) have indicated the presence of at least two distinct types of covalent intermolecular cross- linkages in mature collagen fibrils.One type of cross-linkage is destroyed by hydroxylamine and may be considered to be "ester-like" and a second type is destroyed in cold alkali.It was therefore of
Severity of Remodeling, Myocardial Viability, and Survival in Ischemic LV Dysfunction After Surgical Revascularization
Authors: Robert O. Bonow, Serenella Castelvecchio, Julio A. Panza, Daniel S. Berman, Eric J. Velazquez, Robert E. Michler, Lilin She, Thomas A. Holly, Patrice Desvigne-Nickens, Dragana Kosevic, Miroslaw Rajda, Lukasz Chrzanowski, Marek Deja, Kerry L. Lee, Harvey White, Jae K. Oh, Torsten Doenst, James A. Hill, Jean L. Rouleau, Lorenzo Menicanti
Journal: JACC. Cardiovascular imaging (2015)
Dexamethasone inhibits secretory and cytosolic phospholipases A2 in alveolar macrophages in acute lung injury
Authors: Olga Kuzniatsova
Journal: European Respiratory Journal (2013)

Alveolar macrophages (AM) synthesize secretory and cytosolic phospholipases A2 (cPLA2) – main pulmonary surfactant phospholipids metabolizing enzymes. cPLA2 activity is also important as a first step in prostaglandin biosynthesis.  Purpose of research was to define phospholipases A2 activity during acute lung injury and to estimate the possibility of its correction by glucocorticoids.  Methods: intratracheal administration of bleomycin to rats and radioassay of cytosolic (cPLA2) and secretory phospholipase(sPLA2) activity in AM.  Results. We found increased activity of cPLA2 and sPLA2 in AM at all periods of bleomycin-induced lung injury in rats.  At the first inflammatory period activity of cPLA2 was 167% (p ≤ 0.01) above control. Activity of sPLA2 exceeded the cheking level on 22%. Glucocorticoid dexamethasone (1µM) was found to significantly reduce the activity of cPLA2 (on 35%) and further to inhibit (on 27%) the activation of sPLA2 in AM during inflammatory phase of lung damage. The most prominent effect of dexamethasone on phospholipase activity was found at the period of fibroproliferation (21day), when it decreased activity of cPLA2 on 41% and sPLA2 on 48%  Experiments show, that dexamethasone is an effective inhibitor of intra- and secretory phospholipases from alveolar macrophages, and can prevent the enzymatic degradation of surfactant during the lung injury.
A population-based study of statin, ARB, and ACE inhibitor use on pneumonia-related outcomes
Authors: Eric Mortensen, John Cornell, Laurel Copeland, Brandy Nakashima, Mary Jo Pugh, Marcos Restrepo, Antonio Anzueto
Journal: European Respiratory Journal (2011)

Studies suggest that statins and/or angiotensin converting enzyme inhibitors (ACEI) might be beneficial for some infections. Our purpose was to examine the association of the use of statins, ACEI, and angiotensin–receptor blockers (ARBs) on pneumonia-related outcomes.  We conducted a 5–year national cohort study using US Department of Veterans Affairs data including patients >64 years hospitalized with pneumonia. Outcomes examined included 30-day mortality, need for mechanical ventilation and/or vasopressors. We performed propensity-score matching for all 3 of the medication classes simultaneously adjusting for 40 different potential confounders. Results reported as odds ratios and 95% confidence intervals.  Of 50,119 eligible patients, we matched 11,498 cases with 11,498 controls. Mortality at 30-days was 13%. Overall, 34% used statins, 30% ACEI, and 4% ARBs. After matching no clinically significant imbalances existed between cases/controls. In adjusted models, prior statin use was associated with decreased mortality (0.74, 0.68–0.82) and mechanical ventilation (0.81, 0.70–0.94). Inpatient statin use was associated with decreased mortality (0.68, 0.59–0.78) and mechanical ventilation (0.68, 0.60–0.90). Prior (0.88, 0.80-0.97) and inpatient use (0.58, 0.48–0.69) of ACEI were only associated with decreased mortality. Prior (0.73, 0.58–0.92) and inpatient use (0.47, 0.30–0.72) of ARBs were only associated with decreased mortality.  Use of statins, and to a lesser extent ACEI and ARBs, is associated with improved pneumonia-related outcomes. Additional studies are needed to determine whether the use of these medications in those with pneumonia may be beneficial.
The addition of dexamethasone to bortezomib for patients with relapsed multiple myeloma improves outcome but ongoing maintenance therapy has minimal benefit
Authors: Simon J. Harrison, Hang Quach, Emma Link, Huaibao Feng, Joanne Dean, Michael Copeman, Helgi Van De Velde, Anthony Schwarer, Bartrum Baker, Andrew Spencer, John Catalano, Philip Campbell, Bradley Augustson, Ken Romeril, Henry Miles Prince
Journal: American Journal of Hematology (2015)

Despite the common practice of combining dexamethasone (Dex) with bortezomib (Bz) in patients with multiple myeloma (MM), until now there has been few prospective trials undertaken. We undertook a trial that recapitulated the original APEX study except that dexamethasone was incorporated from cycle 1. We also incorporated an exploratory maintenance component to the study. Twenty sites enrolled 100 relapsed/or refractory MM patients utilizing eight 21 day cycles of IV Bz [1.3 mg/m(2) ; Day (D) 1, 4, 8, 11] and three 35 day cycles; Bz (1.3 mg/m(2) ; Day (D) 1, 8, 15, 22). Our study was registered at www.clinicaltrials.gov (NCT00335348). Patients with stable disease or better received maintenance Bz (1.3 mg/m(2) ) every 14 days until progression. Dexamethasone (20 mg) was given for 2 days with each Bz dose. A prospectively defined matched-analysis of primary (overall response rate; ORR) and secondary endpoints [Complete Response (CR) and time to progression (TTP)] compared our cohort to those on the Bz arm of the APEX trial. The addition of Dex improved ORR by 20% (56% vs. 36%) [odds ratio 0.44 (0.24-0.80)]. The median TTP was also significantly longer (10.1 vs. 5.1 months) (hazard ratio 0.50, 95% CI: 0.35-0.72, P = 0.0002) and our landmark analysis demonstrated that this was largely due to the early use of dexamethasone, as we were unable to demonstrate any benefit of bortezomib/dexamethasone maintenance therapy.
Topical valrubicin application reduces skin inflammation in murine models
Authors: E. Hauge, H. Christiansen, C. Rosada, E. de Darkó, T.N. Dam, K. Stenderup
Journal: British Journal of Dermatology (2012)

Background Valrubicin is a cytostatic anthracycline analogue, lacking toxicity by skin and tissue contact, and represents a new drug with potential for topical treatment of psoriasis and nonmelanoma skin cancer (NMSC); the beneficial effects have been partly explained by its antiproliferative and proapoptotic characteristics. Objectives To assess the effect of valrubicin on skin inflammation as inflammation also plays a key role in psoriasis and NMSC. Methods The effect of topical valrubicin treatment on skin inflammation in vivo was addressed in skin inflammation mouse models, where 12‐O‐tetradecanoylphorbol 13‐acetate was used to induce irritant contact dermatitis. An acute and a chronic model were included, to investigate the effect of valrubicin in short‐term inflammation and in more persistent inflammation. Inflammation‐associated ear oedema was evaluated by measuring ear thickness, infiltration of neutrophil cells, and expression of inflammatory cytokines, interleukin (IL)‐1β and IL‐6. Results Topical valrubicin treatment effectively reduced the inflammatory response in the acute and the chronic models. Conclusions The present data document an anti‐inflammatory effect of valrubicin, and may suggest an interesting new role for valrubicin in other debilitating skin diseases in which inflammation is a significant factor.