tbuckley/cabot-search huggingface dataset:
Randomized, controlled pilot trial of electro-acupuncture for nausea, vomiting, and myelosuppression in women receiving adjuvant chemotherapy for early breast cancer.
Authors: J. M. Beith, B. Oh, K. Orme, A. McLean, M. Chatfield, R. Venkateswaran
Journal: Journal of Clinical Oncology (2010)

e19630 Background: Nausea, vomiting and myelosuppression are common side effects of chemotherapy. Despite recent advances in anti-emetic therapy, a significant percent of women still experience nausea and vomiting. Nonblinded trials have suggested acupuncture may have some benefit in controlling these side effects. The primary objective of this study was to assess feasibility and safety of electro-acupuncture (EA) used in women receiving adjuvant anthracycline based chemotherapy for early breast cancer. Secondary objectives were to assess any benefit of EA on reducing chemotherapy induced nausea, vomiting and myelosuppression. Methods: Thirty women receiving adjuvant anthracycline based chemotherapy for early breast cancer were randomized to receive sham EA (n=16) or real EA (n=14). Acupuncture was administered immediately prior to chemotherapy and on day 2 for the first 2 cycles. All patients received standard anti-emetic therapy. Nausea and vomiting were assessed in the first 3 cycles of chemotherapy with women completing the Multinational Association of Supportive Care in Cancer (MASCC) anti-emetic tool daily for 5 days. WCC and neutrophil counts were measured prior to each chemotherapy and mid cycle for the first 3 cycles. Results: All women completed all planned acupuncture treatments with no adverse events. Complete control of vomiting (79% vs. 69%) was greater in the EA group than the sham group but the opposite was true for nausea (14% vs. 25%). Three patients in the control group experienced febrile neutropenia (FN) compared to one patient in the intervention group. Four patients in the control group received pegfilgrastrin and one in the intervention group because of FN or low neutrophil count prior to chemotherapy. There were significant differences in the WCC (median 6.05 vs. 4.50 ×109/L) and neutrophil (3.55 vs. 1.90 ×109/L) count at week 6. Conclusions: In this pilot study EA was well tolerated. In the treatment arm there were fewer episodes of FN and the use of pegfilgrastrin as well as higher WCC and neutrophil count prior to cycle 3. There was little difference in either nausea or vomiting. A larger trial is planned to assess efficacy. No significant financial relationships to disclose.
Clinical significance of translocation t(1;19) in childhood acute lymphoblastic leukemia in the context of contemporary therapies: a report from the Children's Cancer Group.
Authors: F M Uckun, M G Sensel, H N Sather, P S Gaynon, D C Arthur, B J Lange, P G Steinherz, P Kraft, R Hutchinson, J B Nachman, G H Reaman, N A Heerema
Journal: Journal of Clinical Oncology (1998)

PURPOSE The nonrandom translocation t(1;19) has been associated with poor outcome in pediatric B-lineage acute lymphoblastic leukemia (ALL). Because most patients treated by contemporary therapies now achieve improved outcomes, we have reassessed the prognostic significance of t(1;19). PATIENTS AND METHODS Cytogenetic data were accepted for 1,322 children (&lt;21 years old) with newly diagnosed ALL enrolled between 1988 and 1994 on risk-adjusted studies of the Children's Cancer Group (CCG). Forty-seven patients (3.6%) were t(1;19) positive (+); 1,275 (96.4%) were t(1;19) negative (-). Clinical characteristics and treatment outcome were compared using standard methods. RESULTS Translocation (1;19)+ patients were more likely than t(1;19)- patients to be 10 years of age or greater (P &lt; .001) or CD10+ CD19+ CD34- (P &lt; .0001), or nonwhite (P = .02). Patients with a balanced t(1;19) were less likely to be hyperdiploid than patients with an unbalanced der(19)t(1;19). Event-free survival (EFS) was similar for the overall group of t(1;19)+ and t(1;19)- patients, with 4-year estimates of 69.5% (SD, 6.8%) and 74.8% (SD, 1.3%; P = .48), respectively. However, patients with unbalanced der(19)t(1;19) had significantly better outcomes than patients with balanced t(1;19): 4-year EFS were 80.6% (SD, 7.1%) and 41.7% (SD, 13.5%), respectively (P = .003). These differences were maintained within the individual studies analyses and after exclusion of t(1;19)+ patients whose cells were hyperdiploid with more than 50 chromosomes. CONCLUSION The overall group of t(1;19)+ patients, as well as the subgroup with an unbalanced der(19)+ (1;19) had outcomes similar to that of t(1;19)- patients, whereas patients with balanced t(1;19) had poorer outcomes. Thus, although the overall prognostic significance of t(1;19) has been obviated by contemporary risk-adjusted protocols, the balanced t(1;19) translocation remains an adverse prognostic factor.
Epigenetic control of antiviral and innate immune response following viral infection in a lung epithelial model
Authors: Mirella Cosma Spalluto, Karl J. Staples, Richard McKendry, Tilman Sanchez-Elsner, Tom M.A. Wilkinson
Journal: European Respiratory Journal (2013)

The immune system is controlled by epigenetic mechanisms that modulate responses over the long term and influence disease processes. The impact of respiratory viral infection on epigenetic controls of innate immunity is not yet understood.  We established A549 epithelial cell culture models of acute and chronic Respiratory Syncytial Virus (RSV) infection. We investigated how infection epigenetically modulates the transcription of genes RIG1 involved in antiviral response and TLR4 in innate immune response. The epigenetic analysis was performed using Chromatin Immuno Precipitation (ChIP) with antibodies against histone modifications associated with active promoters: H3K4me3, H3K9ac and RNApolII and repressed promoters: H3K9me3 and H3K27me3.  In A549, acute RSV infection induced a 40-fold increase in RIG1 mRNA at 48h that correlated at his promoter with enrichment of H3K9ac, H3K4me3, RNApolII and reduction of H3K9me3. An increase in TLR4 mRNA was associated with enrichment of H3K9ac and H3K9me3, and H3K4me3 and RNApolII reduction.  In A549 persistently infected with RSV for over 8 months, RIG1 was reduced while TLR4 was increased. Preliminary data show a correlation with epigenetic changes at the gene promoters.  These findings suggest that acute and chronic viral infection leave epigenetic marks, which may lead to differential and long term influences on key inflammatory and innate responses.
Childhood tuberculosis in Romania
Authors: Ramona Nedelcu, Nicoleta Cioran, Elmira Ibraim
Journal: European Respiratory Journal (2012)

Introduction : TB incidence rate in children sharply decreased in Romania in the last decade. TB etiology is difficult to confirm, as the sample for bacteriological examination is obtained in low proportion of cases. For this reason the diagnosis can often be overlooked.   Aim and objectives:  To analyze the trend and the profile of TB epidemic in children in Romania .    Method : The trend of TB incidence rate in children has been observed in Romania in the last decade and all children with TB diagnosis notified in 2009 have been analyzed by gender, residence, age group, treatment history, site and extension of disease, bacteriological status and treatment outcome. Data have been extracted from National TB Register.   Results : TB incidence rate in children failed from 2001 (47.3%ooo) to 2010 (25.3%ooo). In the 965 children registered with TB in Romania in 2009, the male/female ratio was 1.1 and urban/rural ratio 0.87. By age group 49 (5.1%) had less than 1 year, 338 (35%) were in 1-4 years age group and 578 (59.9%) in 5-14 years age group. From the total number of 965, new cases represented 98.7%, 14.9% had severe forms of the disease (30 meningitis, 8 miliaria and 106 with cazeo-cavitary pulmonary lesions), 39.3% had pulmonary TB and of them smear and culture positivity rates were 14% and respectively 25.8%. Of 98 culture positive cases, only 34 (34.7%) had a DST and of them 2 (5.9%) had MDR-TB. Overall outcome was favorable in 96.4% of pulmonary cases, but 2 children deceased, 2 failed and 8 abandoned the treatment.  Conclusion:  Despite the decrease in incidence rate in Romania, there are still many challenges in the control of TB epidemic in childhood, as early detection of cases, proper diagnostic with confirmation of the etiology and successful treatment.
Syk mediates airway contractility independently of leukocyte function
Authors: Jeremy Scott, Xiaomin Wang, Nivedita Khanna, Joyce Wu, Chung-Wai Chow
Journal: European Respiratory Journal (2013)

BACKGROUND:  Syk plays a role in inflammatory diseases such as asthma and rheumatoid arthritis. We reported a role for epithelial expression of Syk in the airways hyperresponsiveness in a mouse model of asthma. These observations led us to posit a role of epithelial Syk in airway contractility.   OBJECTIVE:  To investigate the role of Syk in airway contractility in response to methacholine (MCh).   METHODS:  We used Syk flox/flox //rosa26CreER T2  conditional Syk knockout mice to evaluate respiratory mechanics and MCh-responsiveness  in vivo  using the ventilator-based flexiVent® system, and used live microscopy to assess airway contractility by measuring airway lumen diameter in lung slices  ex vivo .   RESULTS:  In vivo  studies showed that Syk-deficient mice were less responsive to MCh compared with Syk-intact mice. Central airways resistance (R N ) was significantly different between the Syk-intact and Syk-deficient mice (R N (max) : 2.06±0.29 vs 1.29±0.10, respectively, p  ex vivo  lung slices, which are devoid of circulating leukocytes, MCh (100 mg/ml) induced a 20% reduction in the luminal area in the Syk-expressing mice to 80.5±0.6% of baseline. In contrast, MCh-induced contraction of the airways was virtually abrogated in  ex vivo  lung slices obtained from Syk-deficient mice (luminal area 92.2±0.6 % of baseline in Syk-deficient mice, n=4/group, p    CONCLUSIONS:  These observations suggest that Syk mediates AHR independent of its role and function in leukocytes, and supports a potential paracrine role for airway epithelial Syk in modulating airway smooth muscle activity.
AN INTEGRATED MEDICO-PSYCHOLOGICAL PROGRAM AT THE UNITED STATES COAST GUARD ACADEMY
Authors: ROBERT H. FELIX, DALE C. CAMERON, JOSEPH M. BOBBITT, SIDNEY H. NEWMAN
Journal: American Journal of Psychiatry (1945)

1. An integrated medico-psychological program has been developed at the United States Coast Guard Academy. 2. Most of the work has been concerned with the evaluation of officer candidates. 3. Individual interviews by psychiatrist-psychologist teams, objective tests, and questionnaires have been used. 4. Typical results with reserve cadets show (a) That the methods used here make possible an accurate prediction of success and failure in the training school. (b) That objective ability tests and personal interviews are about equally efficient in predicting performance in training. (c) That a combination of interview and test score results is superior to either of these methods alone. 5. The conditions necessary for the effective use of selection methods are discussed.
Treatment of localized aggressive lymphomas with combination chemotherapy followed by involved-field radiation therapy.
Authors: D L Longo, E Glatstein, P L Duffey, D C Ihde, S M Hubbard, R I Fisher, E S Jaffe, M Gilliom, R C Young, V T DeVita
Journal: Journal of Clinical Oncology (1989)

Localized lymphomas of diffuse and aggressive histology sometimes undergo early hematogenous dissemination such that local therapies (surgery alone or followed by radiation therapy) are not curative in 100% of cases. We have treated 47 clinical stage I or IE patients with aggressive lymphoma histologies (diffuse large-cell, diffuse mixed, diffuse immunoblastic, follicular large-cell, diffuse small-non-cleaved cell) with four monthly cycles of an eight-drug combination chemotherapy program consisting of cyclophosphamide, etoposide, doxorubicin, nitrogen mustard (mechlorethamine), procarbazine, high-dose methotrexate with leucovorin rescue, and prednisone (Pro-MACE-MOPP) administered systemically followed by 40 Gy involved-field radiation therapy. Forty-five (96%) patients achieved a complete remission and no patient has relapsed with a median follow-up time of 42 months (range, 8 to 90). Both patients failing to achieve a complete remission died of lymphoma, and one patient died free of lymphoma 45 months after diagnosis during coronary artery bypass surgery unrelated to lymphoma or its treatment. Hospital admissions were necessary to manage complications on nine of 188 (5%) cycles of treatment. There were no treatment-related deaths. ProMACE-MOPP plus involved-field radiation therapy is safe and effective treatment for localized aggressive lymphoma.
Correlating Surrogate Endpoints with Overall Survival at the Individual Patient Level in BRAFV600E-Mutated Metastatic Melanoma Patients Treated with Vemurafenib
Authors: Emily C. Zabor, Glenn Heller, Lawrence H. Schwartz, Paul B. Chapman
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Surrogate endpoints are needed that correlate with overall survival (OS). We analyzed individual patient tumor data from a phase III trial of vemurafenib versus dacarbazine (BRIM3) to identify criteria for tumor measures that correlated with OS. Correlates were validated using a separate data set from a phase II trial of vemurafenib (BRIM2). Experimental Design: Deidentified tumor measurements and OS data from BRIM3 and from BRIM2 were analyzed. Target tumor measurement data and nontarget tumor data were available from pretreatment, weeks 6,12, and every 9 weeks thereafter. In the BRIM3 data set, associations of OS with both early tumor response (first 12 weeks) and time to progression (TTP) were assessed. Different definitions of response and progression were explored. Findings were validated using the BRIM2 data set. Results: Thresholds of early response were explored ranging from any degree of tumor shrinkage to 100% tumor shrinkage. Correlation was weak at all thresholds tested. TTP, however, was more strongly correlated with OS. The strongest correlation was seen when progression was defined as ≥50% increase in the sum of tumor diameters or appearance of new tumors. This was confirmed by similar analyses in the BRIM2 cohort. Conclusions: TTP defined as ≥50% increase in the sum of tumor diameters or appearance of new tumors was more strongly associated with OS than early tumor shrinkage in melanoma patients treated with RAF inhibitor. In future trials, consideration should be given to replacing response rate with TTP or PFS as preferable clinical endpoints in early-phase studies. Clin Cancer Res; 22(6); 1341–7. ©2015 AACR.
<i>RAS</i>and Leukemia: From Basic Mechanisms to Gene-Directed Therapy
Authors: Darrin M. Beaupre, Razelle Kurzrock
Journal: Journal of Clinical Oncology (1999)

PURPOSE AND DESIGN: The purpose of this review is to provide an overview of the literature linking Ras signaling pathways and leukemia and to discuss the biologic and potential therapeutic implications of these observations. A search of MEDLINE from 1966 to October 1998 was performed. RESULTS: A wealth of data has been published on the role of Ras pathways in cancer. To be biologically active, Ras must move from the cytoplasm to the plasma membrane. Importantly, a posttranslational modification—addition of a farnesyl group to the Ras C-terminal cysteine—is a requisite for membrane localization of Ras. Farnesylation of Ras is catalyzed by an enzyme that is designated farnesyltranferase. Recently, several compounds have been developed that can inhibit farnesylation. Preclinical studies indicate that these molecules can suppress transformation and tumor growth in vitro and in animal models, with little toxicity to normal cells. CONCLUSION: An increasing body of data suggests that disruption of Ras signaling pathways, either directly through mutations or indirectly through other genetic aberrations, is important in the pathogenesis of a wide variety of cancers. Molecules such as farnesyl transferase inhibitors that interfere with the function of Ras may be exploitable in leukemia (as well as in solid tumors) as novel antitumor agents.
Recombinant human tumor necrosis factor administered as a five-day continuous infusion in cancer patients: phase I toxicity and effects on lipid metabolism.
Authors: M L Sherman, D R Spriggs, K A Arthur, K Imamura, E Frei, D W Kufe
Journal: Journal of Clinical Oncology (1988)

Recombinant human tumor necrosis factor (rH-TNF) is a cytotoxic monokine with pleiotropic effects. A phase I trial of rH-TNF was initiated using a five-day continuous intravenous (IV) infusion repeated every 28 days. Thirty-eight courses of therapy were administered to 19 patients. The starting dose was 5 X 10(4) U/m2/d, with escalations to 1.0 X 10(5), 2.0 X 10(5), 2.4 X 10(5), and 3.0 X 10(5) U/m2/d. Systemic side effects, including fever, chills, hypotension, fatigue, anorexia, and headaches, were mild and self-limiting. At the maximum tolerated dose of 3.0 X 10(5) U/m2/d, dose-limiting hematologic toxicity was manifested by transient thrombocytopenia and leukopenia. Elevated bilirubin levels were also seen at the higher dose levels. Lipoprotein analysis demonstrated that the five-day treatment with rH-TNF was associated with decreases in high-density lipoproteins, as well as increases in triglycerides and very-low-density lipoproteins. Pharmacokinetic studies using an enzyme-linked immunosorbent assay (ELISA) test indicated plasma rH-TNF levels less than 0.2 U/mL. The recommended phase II dose of rH-TNF administered as a five-day continuous infusion is 2.4 X 10(5) U/m2/d.
Leprosy-associated renal disease
Authors: N Ahsan, D E Wheeler, B F Palmer
Journal: Journal of the American Society of Nephrology (1995)

Leprosy is an infectious disease the principal clinical manifestations of which are anesthetic skin lesions and the development of peripheral neuropathy. The most common renal manifestation in leprosy patients is glomerulonephritis. Both immunofluorescent and electron microscopic studies suggest that the varied glomerular lesions found in these patients are immune complex mediated. Other renal lesions that have been described include amyloidosis, tubulointerstitial disease, acute renal failure, and functional defects in the absence of identifiable histologic abnormalities. In this report, a patient is described who developed the clinical syndrome of rapidly progressive glomerulonephritis. The renal biopsy showed a diffuse endocapillary proliferative process with electron-dense deposits in the glomerular subendothelial and subepithelial spaces. Organisms consistent with Mycobacterium leprae were identified within several of the glomeruli.
Area under the maximum expiratory flow-volume curve a sensitive parameter in the evaluation of airway obstruction
Authors: Lubomir Legath, Marek Varga, Slavomir Perecinsky, Martin Orolin
Journal: European Respiratory Journal (2011)

Introduction: The most frequently used parameters for assessing bronchoconstriction and bronchodilation are forced expiratory volume in 1 s (FEV 1) and peak expiratory flow (PEF).

Objectives: To assess the sensitivity of other parameters after induced bronchoconstriction and bronchodilation.

Methods: Forced vital capacity, FEV 1, PEF, maximum expiratory flows (MEF) at 25, 50 and 75% of vital capacity and the area under the maximal expiratory flow- volumeMEFV curve (Area ex) were measured in two groups of asthmatic patients after induced bronchoconstriction and bronchodilation.

Results: In 158 asthmatics without airway obstruction, bronchoconstriction was induced by inhalation of 1% histamine aerosol. The 20% fall in Area ex compared to baseline was found in all asthmatics, while the 20 and 15% falls in FEV 1 were noted in 31 and 69% of the patients, respectively. Other parameters were less sensitive. Another 102 asthmatics with mild-moderate airway obstruction were treated with various bronchodilators. The 20% increase in Area ex was observed in all asthmatics, while the 20% increase in FEV 1 was found in only 28% of the patients and the 15% increase in FEV 1 in 56%.

Conclusion: In evaluation of correlation between dynamic functional parameters the most accurate parameter is Areaex – value defining surface under the expiratory part of “flow – volume” curve. Area ex was a sensitive parameter in the evaluation of airway patency in comparison withf MEF25, MEF50, MEF75, FEV 1 and other parameters measured from the MEFV curve in our study patients.
Nontuberculous mycobacteria – Respiratory specimens isolation and its clinical significance
Authors: Hans Dabó, Vanessa Santos, Anabela Marinho, Angelica Ramos, Teresa Carvalho, Manuela Ribeiro, Adelina Amorim
Journal: European Respiratory Journal (2014)

Introduction:  Isolation of nontuberculous mycobacteria (NTM) in respiratory specimens often poses challenges to the clinician.   Objective:  Identify and assess the clinical relevance of NTM respiratory isolation (ATS/IDSA criteria).   Methods:  Retrospective analysis of patients (pts) followed in Pulmonology department (Jan/08 to Dec/12), with isolation of NTM in at least one respiratory specimen (Jan/08 to Dec/12). Patients9 identification made by review of medical files.   Results:  202 pts were identified (407 isolates), 58.4% men, mean age 64 years (23-89). Pulmonary comorbidities: COPD 36%, bronchiectasis (BQ) 31% and sequelae of tuberculosis (ST) 20%. The species was identified in 378 pts: MAC 63%,  M.gordonae  11%,  M.peregrinum  9%,  M.chelonae  7%,  M.kansasii  3%,  M.abscessus  3%,  M.scrofulaceum  2% and others 2%. NTM were isolated in sputum in 95% pts, in bronchial lavage in 6%, bronchioalveolar in 4%, lung biopsy in 0.5% and gastric juice in 0.5%. Number of isolates/year: 2008 (52), 2009 (58) 2010 (74), 2011 (86) and 2012 (137). Treatment was performed in 18% pts (89% met the ATS/IDSA criteria): 61% men, mean age 62 years (32-89). Pulmonary comorbidities: COPD 33%, BQ 25% and ST 22%. The MNT treated were MAC in 94% pts,  M. kansasii  in 3% and  M. xenopi  in 3%. Two pts treated for MAC had further treatment for  M. scrofulaceum  and  M. abscessus .   Conclusion:  The majority of patients did not fulfill the criteria for NTM lung disease. The MAC was the most frequently isolated and had greater clinical relevance. The progressive increase in the number of isolations of NTM is probably due to the development of methodologies for detection and increasing respiratory and systemic comorbidities.
The Combined Abuse of Alcohol and Amphetamines
Authors: ALLAN KIPPERMAN, ERIC W. FINE
Journal: American Journal of Psychiatry (1974)

The authors interviewed 15 men who used both alcohol and amphetamines. Clinical histories indicated the existence of two types of abuse patterns—one primarily concerned with the effects of amphetamines and the other with the effects of alcohol. The authors discuss the similarities and differences between these two groups in terms of psychological test results and drug abuse histories. They suggest that the management of this combination syndrome will be different from that for separate alcohol and drug abuse syndromes.