tbuckley/cabot-search huggingface dataset:
Evaluation of high-dose versus standard FAC chemotherapy for advanced breast cancer in protected environment units: a prospective randomized study.
Authors: G N Hortobagyi, G P Bodey, A U Buzdar, D Frye, S S Legha, R Malik, T L Smith, G R Blumenschein, H Y Yap, V Rodriguez
Journal: Journal of Clinical Oncology (1987)

Fifty-nine evaluable patients under 65 years of age with measurable metastatic breast cancer and without prior chemotherapy were randomly assigned to treatment with fluorouracil, Adriamycin (Adria Laboratories, Columbus, OH), and cyclophosphamide (FAC) at standard or high doses (100% to 260% higher than standard FAC) following a dose escalation schedule. Patients randomized to the high-dose FAC received the first three cycles of therapy within a protected environment. Subsequent cycles for this group were administered at standard doses of FAC in an ambulatory setting, the same as for the control group. After reaching 450 mg/m2 of Adriamycin, patients in both groups continued treatment with cyclophosphamide, methotrexate, and fluorouracil until there was disease progression. Analysis of pretreatment patient characteristics showed an even distribution for most known pretreatment factors, although the control group had slightly (but nonsignificantly) more favorable prognostic characteristics. Fourteen patients (24%) achieved a complete remission (CR) and 32 (54%) achieved a partial remission (PR), for an overall major response rate of 78%. There were no differences in overall, CR, or PR rates between the high-dose FAC and control groups. The median response durations were 11 and 10 months for the protected environment and control groups, respectively, and the median survival was 20 months for both groups. Hematologic, gastrointestinal (GI), and infection-related complications were significantly more frequent and severe in the group treated with high-dose chemotherapy. Stomatitis, diarrhea, and skin toxicity were dose-limiting. However, there were no treatment-related deaths. High-dose induction combination chemotherapy with the agents used in this study failed to increase the response rate or survival duration, and resulted in a substantial increase in toxicity.
DNA Microarray Analysis of Labial Salivary Glands in IgG4‐Related Disease: Comparison With Sjögren's Syndrome
Authors: Hiroto Tsuboi, Yuji Nakai, Mana Iizuka, Hiromitsu Asashima, Chihiro Hagiya, Sayaka Tsuzuki, Tomoya Hirota, Haruka Miki, Shinya Hagiwara, Yuya Kondo, Akihiko Tanaka, Masafumi Moriyama, Isao Matsumoto, Seiji Nakamura, Toshio Yoshihara, Keiko Abe, Takayuki Sumida
Journal: Arthritis & Rheumatology (2014)

To compare gene expression in labial salivary glands (LSGs) from patients with IgG4-related disease with that in LSGs from patients with Sjögren's syndrome (SS).Gene expression was analyzed by DNA microarray in LSG samples from 5 patients with IgG4-related disease, 5 SS patients, and 3 healthy controls. Genes differentially expressed in IgG4-related disease and SS were identified, and gene annotation enrichment analysis of these differentially expressed genes was performed using Gene Ontology (GO) annotation. Validation of the results was performed by quantitative polymerase chain reaction (PCR) using LSG samples from 9 patients with IgG4-related disease, 10 SS patients, and 4 controls.Gene expression patterns in patients with IgG4-related disease, SS patients, and healthy controls were quite different from each other in hierarchical clustering as well as in principal components analysis. In IgG4-related disease compared with SS, a total of 1,771 probe sets (corresponding to 1,321 genes) were identified as up-regulated, and 1,785 probe sets (corresponding to 1,320 genes) were identified as down-regulated (false discovery rate of <5%). GO term analysis indicated that the up-regulated set of differentially expressed genes in IgG4-related disease encoded proteins that function in cell proliferation, extracellular matrix organization, and organ development. PCR validated significantly higher expression of lactotransferrin in patients with IgG4-related disease than in SS patients (P < 0.05) and significantly higher expression of CCL18 in patients with IgG4-related disease than in SS patients and controls (P < 0.05).The results clearly showed that the gene expression pattern in LSGs from patients with IgG4-related disease is different from that in LSGs from SS patients.
Restoration of Pulsatile Flow Reduces Sympathetic Nerve Activity Among Individuals With Continuous-Flow Left Ventricular Assist Devices
Authors: William K. Cornwell, Takashi Tarumi, Abigail Stickford, Justin Lawley, Monique Roberts, Rosemary Parker, Catherine Fitzsimmons, Julius Kibe, Colby Ayers, David Markham, Mark H. Drazner, Qi Fu, Benjamin D. Levine
Journal: Circulation (2015)

Background— Current-generation left ventricular assist devices provide circulatory support that is minimally or entirely nonpulsatile and are associated with marked increases in muscle sympathetic nerve activity (MSNA), likely through a baroreceptor-mediated pathway. We sought to determine whether the restoration of pulsatile flow through modulations in pump speed would reduce MSNA through the arterial baroreceptor reflex. Methods and Results— Ten men and 3 women (54±14 years) with Heartmate II continuous-flow left ventricular assist devices underwent hemodynamic and sympathetic neural assessment. Beat-to-beat blood pressure, carotid ultrasonography at the level of the arterial baroreceptors, and MSNA via microneurography were continuously recorded to determine steady-state responses to step changes (200–400 revolutions per minute) in continuous-flow left ventricular assist device pump speed from a maximum of 10 480±315 revolutions per minute to a minimum of 8500±380 revolutions per minute. Reductions in pump speed led to increases in pulse pressure (high versus low speed: 17±7 versus 26±12 mm Hg; P &lt;0.01), distension of the carotid artery, and carotid arterial wall tension ( P &lt;0.05 for all measures). In addition, MSNA was reduced (high versus low speed: 41±15 versus 33±16 bursts per minute; P &lt;0.01) despite a reduction in mean arterial pressure and was inversely related to pulse pressure ( P =0.037). Conclusions— Among subjects with continuous-flow left ventricular assist devices, the restoration of pulsatile flow through modulations in pump speed leads to increased distortion of the arterial baroreceptors with a subsequent decline in MSNA. Additional study is needed to determine whether reduction of MSNA in this setting leads to improved outcomes.
Acute exacerbations in COPD patients are associated with increased levels of hyaluronic acid and heparan sulfate in BAL
Authors: Eleni Papakonstantinou, Ioannis Klagas, Spyros Batzios, Michael Roth, Michael Tamm, Daiana Stolz
Journal: European Respiratory Journal (2014)

BACKGROUND 

Acute exacerbations of COPD (AECOPD) accelerate the deterioration of lung function and remain a major cause of mortality and morbidity.Glycosaminoglycans (GAGs) are essential extracellular matrix molecules that are involved in the pathophysiology of lung diseases.

AIM 

To investigate if AECOPD is associated with differential expression of GAGs in BAL.

METHODS 

94 COPD patients diagnosed with either stable disease (SCOPD) (n=53) or AECOPD (n=44), undergoing diagnostic bronchoscopy were included in this study. Hyaluronic acid (HA), dermatan sulfate (DS), chondroitin sulfate (CS) and heparan sulfate (HS) were measured in BAL by ELISA. The results were correlated with lung function, smoking status, microbiology and demographic characteristics of the patients.

RESULTS 

HA and HS were significantly elevated in BAL of patients with AECOPD as compared to SCOPD (p=0.002 and p=0.031, respectively). Furthermore, in AECOPD, there was a significant negative correlation between HA and CS with FEV1%pred (p=0.031 and p=0.025, respectively) indicating that these GAGs may contribute to airway obstruction.

CONCLUSIONS 

AECOPD are associated with differential expression of specific GAGs such as HA, CS and DS in BAL. These molecules may be proved as potential biomarkers for AECOPD and as alternative targets for pharmacological intervention for the prevention and/or treatment of AECOPD.
Evaluation and Treatment of Pericarditis
Authors: Massimo Imazio, Fiorenzo Gaita, Martin LeWinter
Journal: JAMA (2015)

<h3>Importance</h3> Pericarditis is the most common form of pericardial disease and a relatively common cause of chest pain. <h3>Objective</h3> To summarize published evidence on the causes, diagnosis, therapy, prevention, and prognosis of pericarditis. <h3>Evidence Review</h3> A literature search of BioMedCentral, Google Scholar, MEDLINE, Scopus, and the Cochrane Database of Systematic Reviews was performed for human studies without language restriction from January 1, 1990, to August 31, 2015. After literature review and selection of meta-analyses, randomized clinical trials, and large observational studies, 30 studies (5 meta-analyses, 10 randomized clinical trials, and 16 cohort studies) with 7569 adult patients were selected for inclusion. <h3>Findings</h3> The etiology of pericarditis may be infectious (eg, viral and bacterial) or noninfectious (eg, systemic inflammatory diseases, cancer, and post–cardiac injury syndromes). Tuberculosis is a major cause of pericarditis in developing countries but accounts for less than 5% of cases in developed countries, where idiopathic, presumed viral causes are responsible for 80% to 90% of cases. The diagnosis is based on clinical criteria including chest pain, a pericardial rub, electrocardiographic changes, and pericardial effusion. Certain features at presentation (temperature &gt;38°C [&gt;100.4°F], subacute course, large effusion or tamponade, and failure of nonsteroidal anti-inflammatory drug [NSAID] treatment) indicate a poorer prognosis and identify patients requiring hospital admission. The most common treatment for idiopathic and viral pericarditis in North America and Europe is NSAID therapy. Adjunctive colchicine can ameliorate the initial episode and is associated with approximately 50% lower recurrence rates. Corticosteroids are a second-line therapy for those who do not respond, are intolerant, or have contraindications to NSAIDs and colchicine. Recurrences may occur in 30% of patients without preventive therapy. <h3>Conclusions and Relevance</h3> Pericarditis is the most common form of pericardial disease worldwide and may recur in as many as one-third of patients who present with idiopathic or viral pericarditis. Appropriate triage and treatment with NSAIDs may reduce readmission rates for pericarditis. Treatment with colchicine can reduce recurrence rates.
Psychological and social aspects of the surgical treatment of obesity
Authors: Albert J. Stunkard, James L. Stinnett, Jordan W. Smoller
Journal: American Journal of Psychiatry (1986)

New surgical procedures have revolutionized the treatment of morbid obesity (more than 100% overweight), a condition associated with serious medical complications and for which conservative treatment has been largely ineffective. These procedures, which are surprisingly safe, produce large weight losses and marked improvement in hypertension, diabetes, and other disorders influenced by obesity. Striking changes also occur in vocational and psychosocial functioning, including marital and sexual relations, in eating behavior, in food preferences, and in body image. The emotional state of patients during weight loss following surgery is far superior to that during attempts at weight reduction by other methods. The surgical procedures appear to produce a major biological change, perhaps lowering a body weight set point.
Complex karyotype, older age, and reduced first‐line dose intensity determine poor survival in core binding factor acute myeloid leukemia patients with long‐term follow‐up
Authors: Federico Mosna, Cristina Papayannidis, Giovanni Martinelli, Eros Di Bona, Angela Bonalumi, Cristina Tecchio, Anna Candoni, Debora Capelli, Andrea Piccin, Fabio Forghieri, Catia Bigazzi, Giuseppe Visani, Renato Zambello, Lucia Zanatta, Francesca Volpato, Stefania Paolini, Nicoletta Testoni, Filippo Gherlinzoni, Michele Gottardi
Journal: American Journal of Hematology (2015)

Approximately 40% of patients affected by core binding factor (CBF) acute myeloid leukemia (AML) ultimately die from the disease. Few prognostic markers have been identified. We reviewed 192 patients with CBF AML, treated with curative intent (age, 15–79 years) in 11 Italian institutions. Overall, 10‐year overall survival (OS), disease‐free survival (DFS), and event‐free survival were 63.9%, 54.8%, and 49.9%, respectively; patients with the t(8;21) and inv(16) chromosomal rearrangements exhibited significant differences at diagnosis. Despite similar high complete remission (CR) rate, patients with inv(16) experienced superior DFS and a high chance of achieving a second CR, often leading to prolonged OS also after relapse. We found that a complex karyotype (i.e., ≥4 cytogenetic anomalies) affected survival, even if only in univariate analysis; the KIT D816 mutation predicted worse prognosis, but only in patients with the t(8;21) rearrangement, whereas FLT3 mutations had no prognostic impact. We then observed increasingly better survival with more intense first‐line therapy, in some high‐risk patients including autologous or allogeneic hematopoietic stem cell transplantation. In multivariate analysis, age, severe thrombocytopenia, elevated lactate dehydrogenase levels, and failure to achieve CR after induction independently predicted longer OS, whereas complex karyotype predicted shorter OS only in univariate analysis. The achievement of minimal residual disease negativity predicted better OS and DFS. Long‐term survival was observed also in a minority of elderly patients who received intensive consolidation. All considered, we identified among CBF AML patients a subgroup with poorer prognosis who might benefit from more intense first‐line treatment. Am. J. Hematol. 90:515–523, 2015. © 2015 Wiley Periodicals, Inc.
Genetic variation in the cytochrome P450 2C9 enzyme and dose of Celecoxib in the prevention of colorectal adenoma
Authors: Andrew Chan, Ann Zauber, Meier Hsu, Aurora Breazna, David Hunter, Rebecca Rosenstein, Craig Eagle, Ernest Hawk, Monica Bertagnolli
Journal: Clinical Cancer Research (2008)

B32    Background:  In a randomized trial, the cyclooxygenase-2 inhibitor celecoxib reduced, in a dose-dependent manner, the occurrence of newly detected colorectal adenomas but was associated with an increase in cardiovascular events. Genetic variants in the cytochrome P450 2C9 (CYP2C9) enzyme, particularly the I359L allele, are associated with impaired metabolism of celecoxib and may influence dose-related response or toxicity.   Methods:  In the Adenoma Prevention with Celecoxib trial, 2,035 participants with a history of prior adenoma were randomized to placebo, 200 mg, or 400 mg of celecoxib twice daily. We genotyped 1660 participants for the I359L as well as R144C variant alleles of CYP2C9; 1497 patients underwent evaluation with at least one follow-up colonoscopy at 1 and 3 years for the occurrence of newly detected adenomas.   Results:  Compared with placebo, celecoxib treatment at either the twice-daily 200 mg and 400 mg dose was associated with an overall lower three-year cumulative incidence of adenoma among participants with either wild-type or variant genotypes (≥ one R144C or I359L allele). However, the additional benefit of the higher dose was observed primarily among those with I359 genotypes. Among 183 participants with I359L genotypes, treatment with the 400 mg dose was significantly associated with reduced adenoma incidence compared with the 200 mg dose (RR 0.54; 95% CI, 0.31-0.92; p=0.02). In contrast, treatment with the 400 mg dose was not associated with a significantly greater reduction in adenoma incidence compared with the 200 mg dose among the 318 participants with R144C genotypes (RR 0.93; 95% CI, 0.64-1.36; p=0.72) or the 996 participants with wild-type genotypes (RR 0.88; 95% CI, 0.71-1.11; p=0.28). Among participants with I359L genotypes, the three-year cumulative incidence of investigator-reported, treatment-emergent, cardiovascular events was 4.4% for placebo, 3.4% for 200 mg, and 13.3% for 400 mg. The cumulative incidence of cardiovascular events was 3.9% for placebo, 2.8% for 200 mg, and 9.4% for 400 mg among participants with R144C genotypes and 5.7% for placebo, 9.6% for 200 mg, and 8.1% for 400 mg among participants with wild-type genotypes.   Conclusions:  Chemoprevention with celecoxib appears to be modified by genetic variation in its metabolism. Individuals with CYP2C9 variant I359L genotypes may benefit differentially according to celecoxib dose.
Standardization of single-breath transfer factor (TLCO); derivation of breathholding time
Authors: DJ Chinn, R Harkawat, JE Cotes
Journal: European Respiratory Journal (1992)

Breathholding time is usually defined using the procedure of Ogilvie et al. or of Jones and Meade; these procedures depend on knowing when inspiration begins and, for the latter, when it ends. Some alternative procedures do not require this information. With a view to standardizing the measurement, transfer factor of the lungs for carbon monoxide (TLCO) was measured in 18 adults with labile airflow obstruction, who were assessed before and after inhalation of salbutamol. The inflection points defining the start and end of inspiration were defined visually (method 1), and by extrapolation of the linear part of the inspiratory limb of the single-breath trace (method 2). The spirograms met recognized standards of quality and were rated by experienced observers. Compared with method 1 the TLCO and related indices by method 2 were lower using the procedure of Jones and Meade and higher using the procedure of Ogilvie et al. in each case by, on average, 1.0%. The within- and between-day variabilities were independent of the method used. Thus, the extrapolation and visual methods yielded interchangeable results when applied by experienced operators. However, extrapolation may be easier for inexperienced operators.
Clinical course of breast cancer patients with liver metastases.
Authors: J W Zinser, G N Hortobagyi, A U Buzdar, T L Smith, G Fraschini
Journal: Journal of Clinical Oncology (1987)

Between June 1973 and November 1980, 1,171 patients with metastatic breast cancer were treated with various doxorubicin-containing regimens at our institution (M.D. Anderson Hospital and Tumor Institute, Houston). Retrospective analysis of all 233 cases (20%) with liver metastases was done to correlate various clinical and biochemical characteristics with response to treatment, survival, and causes of death. A similar analysis was performed for 58 consecutive patients with liver metastases treated at this hospital between December 1955 and December 1957 with hormone therapy or single-agent chemotherapy. Objective responses were observed in 132 of 233 patients (57%) treated with combination chemotherapy. The median survival was 14 months in the 1970s and 5 months in the 1950s. Among patients who had liver metastases at the time of initial diagnosis of breast cancer, survival was longer for the group treated with combination chemotherapy. All cases were classified according to the number of organ sites involved by metastases. Patients with only liver metastases, or liver plus bone lesions had the longest survival. Other clinical and biochemical factors that correlated significantly with longer survival were: no prior chemotherapy, performance status of 1 to 2, absence of ascites, normal bilirubin and lactic dehydrogenase (LDH), SGOT less than or equal to 2 times normal and albumin greater than 4.5 g/dL. The main cause of death was multiorgan failure, with only 20% of patients dying of liver failure. The present study shows that the presence of liver metastases in breast cancer is not by itself an ominous factor. Most patients respond to therapy, and significant palliation with extended survival is possible for several prognostic subgroups. Further improvement in length and quality of survival is expected with earlier diagnosis.
Clinical Activity of Trastuzumab and Vinorelbine in Women With HER2-Overexpressing Metastatic Breast Cancer
Authors: Harold J. Burstein, Irene Kuter, Susana M. Campos, Rebecca S. Gelman, Laura Tribou, Leroy M. Parker, Judith Manola, Jerry Younger, Ursula Matulonis, Craig A. Bunnell, Ann H. Partridge, Paul G. Richardson, Kathryn Clarke, Lawrence N. Shulman, Eric P. Winer
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine the response rate and toxicity profile of trastuzumab administered concurrently with weekly vinorelbine in women with HER2-overexpressing advanced breast cancer. PATIENTS AND METHODS: Forty women with HER2-positive (+3 by immunohistochemistry, n = 30; +2 or positive, n = 10) breast cancer were enrolled onto a study of trastuzumab (4 mg/kg × 1, 2 mg/kg weekly thereafter) and vinorelbine (25 mg/m 2 weekly, with dose adjusted each week for neutrophil count). Eighty-two percent of women had received prior chemotherapy as part of adjuvant (30%), metastatic (25%), or both (28%) treatment, including substantial portions of patients who had previously received either anthracyclines (20%), taxanes (15%), or both types (38%) of chemotherapy. RESULTS: Responses were observed in 30 of 40 patients (overall response rate, 75%, conditional corrected 95% confidence interval, 57% to 89%). The response rate was 84% in patients treated with trastuzumab and vinorelbine as first-line therapy for metastatic disease, and 80% among HER2 +3 positive patients. High response rates were also seen in women treated with second- or third-line therapy, and among patients previously treated with anthracyclines and/or taxanes. Combination therapy was feasible; patients received concurrent trastuzumab and vinorelbine in 93% of treatment weeks. Neutropenia was the only grade 4 toxicity. No patients had symptomatic heart failure. Grade 2 cardiac toxicity was observed in three patients. Prior cumulative doxorubicin dose in excess of 240 mg/m 2 and borderline pre-existing cardiac function were associated with grade 2 cardiac toxicity. CONCLUSION: Trastuzumab in combination with vinorelbine is highly active in women with HER2-overexpressing advanced breast cancer and is well tolerated.
Respiratory morbidity in moderate to late preterm infants during the first three years of life: SAREPREM 3235 study
Authors: Antonio Moreno-Galdó, Eduardo G. Pérez-Yarza, Octavio Ramilo, Asunción Mejías
Journal: European Respiratory Journal (2014)

Objectives.  To determine the incidence and risk factors associated with recurrent wheezing (RW) in a Spanish birth cohort of infants born at 32-35 weeks of gestation.   Methods.  Prospective, longitudinal multicenter study of preterm infants (32-35 w) followed until 3 years of age. Development of physician-diagnosed RW (≥ 3 episodes/year) was assessed and multivariable logistic regression analyses performed to identify independent risk factors associated with RW.   Results.  977 infants were enrolled. Table 1 displays the incidence of RW over the study period.  Day care attendance was consistently identified as a risk factor (OR [95% CI]) for RW at 1 year (3.73, [2.30-6.03]), 2 years (2.21 [1.42-3.45]) and 3 years of age (2.90 [1.32-6.35]). Parental asthma (1 year; (1.94 [1.14-3.30]), and 3 years; (1.96 [1.07-3.60]), or acetaminophen use ≥ 1/pregnancy trimester (2 years (1.87[1.17-3.00]) and 3 years (1.95[1.15-3.31]) were identified as a risk factors at most ages. Lastly, at 1 year of age low birth weight (1.71, [1.06-2.76]) and school-age siblings (1.72 [1.10-2.71]) and at 3 years of age male gender (2.0 [1.18-3.33]) and animal contact during pregnancy (2.66 [1.02-6.93]) were also independenly associated with RW. Only palivizumab prophylaxis was shown to be protective for the development of RW at 3 years of age (0.30 [0.12-0.75]).   Conclusions.  Moderate to late preterm infants demonstrated significant respiratory morbidity during the first three years of life associated with several modifiable and non-modifiable risk factors.