tbuckley/cabot-search huggingface dataset:
Secondary malignancies in chronic myeloid leukemia patients after imatinib-based treatment: long-term observation in CML Study IV
Authors: M B Miranda, M Lauseker, M-P Kraus, U Proetel, B Hanfstein, A Fabarius, G M Baerlocher, D Heim, D K Hossfeld, H-J Kolb, S W Krause, C Nerl, T H Brümmendorf, W Verbeek, A A Fauser, O Prümmer, K Neben, U Hess, R Mahlberg, C Plöger, M Flasshove, B Rendenbach, W-K Hofmann, M C Müller, M Pfirrmann, A Hochhaus, J Hasford, R Hehlmann, S Saußele
Journal: Leukemia (2016)

Treatment of chronic myeloid leukemia (CML) has been profoundly improved by the introduction of tyrosine kinase inhibitors (TKIs). Long-term survival with imatinib is excellent with a 8-year survival rate of ∼88%. Long-term toxicity of TKI treatment, especially carcinogenicity, has become a concern. We analyzed data of the CML study IV for the development of secondary malignancies. In total, 67 secondary malignancies were found in 64 of 1525 CML patients in chronic phase treated with TKI (n=61) and interferon-α only (n=3). The most common malignancies (n⩾4) were prostate, colorectal and lung cancer, non-Hodgkin's lymphoma (NHL), malignant melanoma, non-melanoma skin tumors and breast cancer. The standardized incidence ratio (SIR) for all malignancies excluding non-melanoma skin tumors was 0.88 (95% confidence interval (0.63–1.20)) for men and 1.06 (95% CI 0.69–1.55) for women. SIRs were between 0.49 (95% CI 0.13–1.34) for colorectal cancer in men and 4.29 (95% CI 1.09–11.66) for NHL in women. The SIR for NHL was significantly increased for men and women. An increase in the incidence of secondary malignancies could not be ascertained. The increased SIR for NHL has to be considered and long-term follow-up of CML patients is warranted, as the rate of secondary malignancies may increase over time.
The polyamine spermine inhibits mitochondrial permeability transition (mPT) and apoptosis in human eosinophils
Authors: Pinja Ilmarinen, Eeva Moilanen, Jonas S. Erjefält, Hannu Kankaanranta
Journal: European Respiratory Journal (2014)

Background:  Eosinophil accumulation into the airways is characteristic for most phenotypes of asthma. Spermine, spermidine and putrescine are ubiquitous cationic polyamines with basic functions related to nucleic acid packaging, DNA replication, apoptosis, transcription and translation. Polyamine levels are elevated in serum and sputum from patients with asthma suggesting a role in the disease.  Objective:  The aim of the present study was to examine if polyamines, especially spermine, regulate eosinophil survival which is a significant factor contributing to airway eosinophilia.  Methods:  Eosinophils were isolated from venous blood of eosinophilic donors. Apoptosis was determined by transmission electron microscopic (TEM) analysis and DNA fragmentation assay. Mitochondrial permeability transition (mPT) was determined by calcein/CoCl 2  staining. Luminescence and fluorometric assays were used to measure activities of caspases.  Results:  Apoptosis-related DNA fragmentation was prevented by spermine (10-1000 µM) and spermidine (100-1000 µM) but not putrescine. TEM analysis confirmed the survival-prolonging effect of spermine and showed that its efficiency in enhancing survival was close to that of GM-CSF. Spermine and spermidine inhibited also mitochondrial permeability transition (mPT) while putrescine had no effect. Futhermore, spermine reduced activities of caspases.  Conclusions:  The present results introduce spermine as a novel eosinophil survival-prolonging factor associated with asthma and the mechanism seems to involve inhibition of mitochondrial permeability transition and suppression of caspase activity.
Radical treatment with weekly cisplatin (wCDDP) plus concurrent radiotherapy (XRT) in locally advanced cervical cancer (LACC) patients (pts): A mono-institutional experience.
Authors: V. Murgia, C. Arcuri, O. Caffo, V. Vanoni, E. Magri, E. Bagatin, A. Caldara, E. Arisi, E. Galligioni
Journal: Journal of Clinical Oncology (2010)

e15556 Background: Platinum-based radical chemoradiation is the standard treatment for LACC (stage Ib2-IV) pts. We describe in this report the activity and tolerability concurrent wCDDP and XRT in LACC pts treated in our Department. Methods: Between May 2001 and July 2009, we have treated a consecutive series of 40 patients with whole pelvic external XRT (plus XRT boost in patients with parametrial invasion) and brachytherapy (B) in selected cases (with good clinical response to external XRT). We administered weekly CDDP at the dose of 40 mg/sqm for a total of 4-6 courses, starting on XRT day 1. Results: Pts characteristics were: median age 54 yrs (30-78); median PS 0 (0-2); FIGO stage: Ib2 in 5 pts, IIb in 15, IIIa in 1, IIIb in 13, IVa in 3, and IVb (without visceral metastasis) in 3. Histology: squamous in 33 pts and adenocarcinoma in 5, undifferentiated in 1, and unknown in 1.The pts received an external XRT for a median total dose of 50.4 Gy (range 40-67); XRT boost was delivered in 7 cases (median dose 0.9 Gy; range 0.6-1.8); B was performed in 20 pts, who received a B dose ranging from 10.5 to 33.5 Gy (median 30). The treatment was completed in 82.5% of the pts. The median number of delivered CT courses was 5 (range 1-8). Major acute toxicities consisted of grade 3 neutropenia (2 pts), grade 3 anemia (1 pt), grade 3 diarrhoea (1 pt), grade 3 constipation (1 pt), grade 3 fatigue (1 pt). In one case, a blood transfusion was required. We observed one case of febrile neutropenia (requiring GCSF), without major infection. According to the LENT-SOMA toxicity score, we observed the following XRT-related late toxicities: grade 1/2 rectal in 3/1 pts respectively, grade 2 urinary in 1 pt, grade 2 sexual in 1 pt, grade 2 bone in 1 pt. The response rate was 95 % (6 CR and 32 PR). After a median follow-up of 27 mos (range 4-75), the 2-year OS and DFS were 94.4 % and 77.2 % respectively, with median OS and DFS not reached. Conclusions: Our experience with concurrent wCDDP + XRT in LACC confirms the good activity and tolerability of this treatment and appears super imposable to the literature data. No significant financial relationships to disclose.
Abstract P057: Adiposity Associated Inflammation and Hypertension
Authors: Matthew A Allison, Cindy Morgan, Dena Rifkin, Michael H Criqui
Journal: Circulation (2012)

Background: The aim of this study was to test whether selected markers of adiposity associated inflammation (adipokines) are associated with hypertension (HTN) and isolated systolic hypertension (ISH). Methods: Subjects were 1970 individuals who were enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). Subjects provided a wide range of health history information and had several physical measurements performed. Blood pressure was measured three times using a standard protocol, with the last two measurements being averaged. HTN was defined as a systolic blood pressure (SBP) &gt; 140 mmHg, diastolic blood pressure (DBP) &gt; 90 or taking a blood pressure medication while ISH was SBP &gt; 140 or taking a blood pressure medication and a DBP &lt;= 90. Fasting venous blood collected at this visit was analyzed for the following adipokines: leptin, adiponectin, tumor necrosis factor - alpha and resistin. Results: The mean age was 64.7 years and 50% were female. The mean SBP, DBP, mean arterial pressure (MAP) and pulse pressure (PP) was 124, 70, 88 and 54 mmHg, respectively. Forty-four percent had HTN. The Table shows the results of multivariable logistic regression for the adipokines and both HTN and ISH. As shown, leptin was consistently associated with a significantly higher odds for the presence of either HTN and ISH. This applies to whether leptin was utilized as a continuous or categorical variable (in quartiles). Adding body mass index to model #3 modestly attenuated the associations, but remained statistically significant (p ≤ 0.01 for all). Associations for the other adipokines were inconsistent and not significant after full adjustment. Conclusion: Higher leptin, but not the other adipokines studied, is significantly associated with diagnoses of both hypertension and isolated systolic hypertension independent of relevant covariates including body mass index. This suggests that leptin may have an influence on blood pressure beyond the effects of adiposity.
Characterization of Human Malignant Melanoma Cell Lines. I. Morphology and Growth Characteristics in Culture&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: S K Liao, P B Dent, P B McCulloch
Journal: JNCI Journal of the National Cancer Institute (1975)

Seven human malignant melanoma lines were maintained in vitro for various periods of time. One line, established in this laboratory from a metastatic solid tumor by repeated treatment of the primary outgrowth with 0.02 percent EDTA, allowed a continuous culture of melanoma cells free of fibroblasts. By light microscopy, cells in each line could be classified into one of three morphologic types: elongated dendritic, cuboidal, or triangular dendritic. Four of the seven lines exhibited various degrees of pigmentation. The growth pattern was determined by plating efficiency and saturation density for each line. Cytogenetic analysis with the fluorescent banding technique revealed only human chromosomes with gross aneuploidy. Major marker chromosomes specific for each line were identified. None of the parameters studied showed any correlation or interdependence with one another, except for an association of elongated dendritic morphology with poor plating efficiency and low saturation density.
Internal airflow distribution is driven by lobar volume, hyperinflation and emphysema score in COPD patients
Authors: Wilfried De Backer, Cedric Van Holsbeke, Rita Claes, Annemie Hufkens, Lieven Bedert, Peter van Hal, Jan De Backer, Wim Vos
Journal: European Respiratory Journal (2014)

Rationale 

COPD is characterized by tissue and airway wall inflammation, distortion and destruction (emphysema, small airway disease). This trial tries to identify the influence of hallmark characteristics of COPD on regional ventilation in patients.

Methods 

For 28 patients (21M, 66.3±6.4y, 8/18/2 GOLD II/II/IV, FEV1=43.9±11.9%p) FRI-based regional measures on lobar volume, hyperinflation, perfusion, emphysema and ventilation were obtained from breathing gated HRCT scans at FRC and TLC. A generalized estimating equation was fit to the data in order to predict regional ventilation in function of the other parameters, correcting for lobar repeated measures within a patient.

Results 

A positive correlation was found between regional ventilation and static lung volume (p<0.001). Emphysema (p=0.017) and hyperinflation (p=0.028), independently, have a negative correlation with ventilation, while perfusion does not have a direct influence on ventilation (p=0.98).

![Figure][1] 



Conclusions 

It could be seen that airflow distribution is mainly driven by the static lobe volume, i.e. larger lobes attract more air than smaller lobes. However, this correlation is counteracted by the presence of emphysema and/or other reasons for hyperinflation. This means that also hyperinflated regions with predominant small airways disease receive less ventilation and hence a less optimal distribution of inhaled treatments.

This study was funded by Takeda.

 [1]: pending:yes
Preterm birth and inhaled corticosteroid usage in 6-19-year-olds – A Swedish national cohort study
Authors: Hartmut Vogt, Karolina Lindström, Lennart Bråbäck, Anders Hjern
Journal: European Respiratory Journal (2011)

Objective: Preterm birth is associated with respiratory morbidity later in life, including asthma. Previous studies have mainly focused on asthma in early childhood in children born extremely preterm. In this study we examined the risk of asthma in a national cohort of school children by degree of immaturity expressed as completed gestational weeks at birth.

Methods: Register study in a Swedish national cohort of 1 100 826 children 6-19 years old. Retrieval of at least one prescription of inhaled corticosteroids (ICS) during 2006 was used as our main indicator for asthma. Logistic regression was used to test hypotheses with adjustment for multiple socio-economic and perinatal indicators.

Results: Degree of immaturity, expressed as completed gestational weeks at birth, had an inverse dose-response relationship with ICS usage. Compared to children born between 39 and 41 weeks gestation, the odds ratio for ICS usage increased with the degree of prematurity, from 1.10 (1.08-1.13) for children born in weeks 37-38, to 2.28 (1.96-2.64) for children born in weeks 24-28, after adjustment for socio-economic confounders and perinatal mediators.

The increase in ICS usage with decreasing gestational age at delivery was similar in boys and girls and declined with older age.

Conclusion: Preterm birth increases the risk of ICS usage in 6-19 year olds by degree of immaturity, all the way from extremely preterm to early term birth.
Sudden Deaths Among Oil and Gas Extraction Workers Resulting from Oxygen Deficiency and Inhalation of Hydrocarbon Gases and Vapors — United States, January 2010–March 2015
Authors: Robert J. Harrison, Kyla Retzer, Michael J. Kosnett, Michael Hodgson, Todd Jordan, Sophia Ridl, Max Kiefer
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

In 2013, an occupational medicine physician from the University of California, San Francisco, contacted CDC's National Institute for Occupational Safety and Health (NIOSH), and the Occupational Safety and Health Administration (OSHA) about two oil and gas extraction worker deaths in the western United States. The suspected cause of these deaths was exposure to hydrocarbon gases and vapors (HGVs) and oxygen (O2)-deficient atmospheres after opening the hatches of hydrocarbon storage tanks. The physician and experts from NIOSH and OSHA reviewed available fatality reports from January 2010 to March 2015, and identified seven additional deaths with similar characteristics (nine total deaths). Recommendations were made to industry and regulators regarding the hazards associated with opening hatches of tanks, and controls to reduce or eliminate the potential for HGV exposure were proposed. Health care professionals who treat or evaluate oil and gas workers need to be aware that workers might report symptoms of exposure to high concentrations of HGVs and possible O2 deficiency; employers and workers need to be aware of this hazard and know how to limit exposure. Medical examiners investigating the death of oil and gas workers who open tank hatches should consider the contribution of O2 deficiency and HGV exposure.
Clinical guidelines and indications for bronchoalveolar lavage (BAL): chronic bronchitis and emphysema
Authors: E Pozzi, V De Rose, SI Rennard, LM Fabbri
Journal: European Respiratory Journal (1990)

In agreement with the recent state-of-the-art paper and review articles, we believe that there is no indication at present for the use of bronchoalveolar BAL 959 lavage in clinical practice for the diagnosis, staging, monitoring or therapy of bronchial asthma.The only indication that may prove to be clinically helpful is the presence of pulmonary infiltrates in asthmatics, particularly for the diagnosis of allergic bronchopulmonary aspergillosis.
Phase II study of single-agent vinflunine in platinum-refractory transitional cell carcinoma of the urothelium (TCCU)
Authors: D. J. Vaughn, S. Srinivas, W. M. Stadler, R. Pili, D. Petrylak, S. De Marco, D. C. Smith, S. Nason, E. De Wit, C. George
Journal: Journal of Clinical Oncology (2007)

15543 Background: Vinflunine (VFL) is a new microtubule inhibitor of the vinca alkaloid class with clinical activity in TCCU (S. Culine, BJC 2006). This trial was conducted to define VFL activity in platinum-refractory TCCU patients (pts). Methods: Multicenter, single-arm study. Primary endpoint: Objective response rate (Independent Review; WHO criteria). Planned sample size: 150 pts. Main pt eligibility: at least one measurable lesion; documented progression within 12 months of last dose of platinum-containing regimen; calculated creatinine clearance (Cr Cl) = 20 mL/min. VFL 320 mg/m 2 IV infusion over 20 minutes was administered every 3 weeks. In pts with poor performance status, prior pelvic irradiation, or renal impairment (Cr Cl 20–60 mL/min), initial dose (ID) was 280 mg/m 2 , escalated to 320 mg/m 2 if well tolerated. Results: Enrollment of 150 pts complete. Baseline pt characteristics (first 118 pts treated): Gender: male 78%, female 22%. Median age: 66 years (range 40–83). Renal impairment: 32%. Prior chemotherapy: cisplatin: 69%; carboplatin: 47%, gemcitabine: 94%. Total of 402 VFL cycles administered (range: 1–12). 320 mg/m 2 ID: 35 pts; 280 mg/m 2 ID: 83 pts. Main toxicity was hematologic (Grade (G) 3/4): neutropenia: 19%/37%; thrombocytopenia: 3%/0%; anemia: 13%/0%; febrile neutropenia: 320 mg/m 2 ID: 5 pts; 280 mg/m 2 ID: 3 pts. Main non-hematologic toxicities: constipation: 320 mg/m 2 ID: 63% (G3/4: 14%/3%); 280 mg/m 2 ID: 59% (G3/4: 12%/1%); fatigue: 320 mg/m 2 ID: 43% (G3/4: 6%/0%); 280 mg/m 2 ID: 35% (G3/4: 7%/0%). Severe diarrhea or vomiting was infrequent. No G3/4 peripheral neuropathy was noted. Responses have been observed by the investigators, but independent review is on-going. Conclusions: VFL has a manageable toxicity profile in pts with platinum-refractory TCCU. Independently reviewed response rate and other efficacy endpoints of the entire cohort will be presented. No significant financial relationships to disclose.
Pretest counselling and informed consent should be prerequisites
Authors: A. Edwards
Journal: BMJ (1996)

EDITOR,—Neonatal screening is justifiable if the individual screening tests have been assessed against criteria of suitability.1 For its implementation to be ethical, however, a further component is required: adequate pretest counselling and informed consent.

Neonatal screening has potential for rapid expansion, yet there is little evidence that even those tests recently included in …
IgG4 Drives M2 Macrophages to Cortisol, Lcn-2 and IL-10 Release: Implications in Maintenance of Tolerance and Allergen Immunotherapy
Authors: Erika Jensen-Jarolim, Franziska Roth-Walter, Luis F. Pacios, Stefanie Wagner, Lisa-Maria Glenk, Gerlinde Hofstetter, Rupert Palme, Georg A. Roth, Karin Hufnagl, Rodolfo Bianchini
Journal: Journal of Allergy and Clinical Immunology (2016)
Nut Allergy Prevalence and Differences Between Asian-Born Children and Australian-Born Children of Asian Descent: A State-Wide Survey of Children at Primary School Entry in Victoria, Australia
Authors: Katrina Jane Allen, Mary Panjari, Jennifer Koplin, Shyamali Dharmage, Rachel L. Peters, Lyle Gurrin, Susan Sawyer, Vicki L. McWilliam, Jana K. Eckert, Don Vicendese, Bircan Erbas, Melanie C. Matheson, Mimi L.K. Tang, Jo Douglass, Anne-Louise Ponsonby, Terry Dwyer, Sharon Goldfeld
Journal: Journal of Allergy and Clinical Immunology (2016)
Preoperative gemcitabine (G) and docetaxel (D) in patients (pts) with stage IB, II, or III non-small cell lung cancer (NSCLC): A phase II trial of the Minnie Pearl Cancer Research Network
Authors: D. R. Spigel, J. D. Hainsworth, D. A. Yardley, H. A. Burris, D. S. Thompson, J. D. Zubkus, S. Litchy, D. Silverberg, J. R. Thomas, F. A. Greco
Journal: Journal of Clinical Oncology (2006)

17007 Background: Preoperative chemotherapy may improve outcomes for pts with resectable NSCLC compared with surgery alone. This multicenter community-based phase II trial examined the role of preoperative G/D for pts with resectable NSCLC. Methods: The primary endpoint was to assess the response rate (RR) of G/D in pts with potentially resectable clinical stages IB, II, and selected III NSCLC [T 3 N 1 , T 1–3 N 2 (1 nodal station ≤2 cm), T 4 N 0, T 4 N 1 excluding vascular, tracheal, esophageal, vertebral disease, or malignant effusions]. Treatment included: D 30 mg/m 2 IV and G 1000 mg/m 2 IV D1,8 Q 21D × 3 cycles. Pts were restaged after treatment and resected 3–6 weeks later. Eligibility included: measurable disease, ECOG PS 0–1, adequate organ function, informed consent. Analysis was by intent to treat. Results: Fifty-four pts were enrolled between 4/04 and 9/05. Baseline features include: median age 62 years (42–82); male/female, 44%/56%; ECOG PS 0/1: 50%/50%; adenocarcinoma (28%), squamous (43%), large cell (9%), mixed/not specified (20%); IB (30%), IIA (5%), IIB (19%), IIIA (33%), IIIB (13%). Forty-eight pts (91%) completed preoperative treatment and 32 pts (60%) underwent resection. Grade 3/4 hematologic and non-hematologic toxicities were limited to neutropenia (20%) and infection (8%), respectively. All other toxicities were &lt;5%. There were no treatment-related deaths. Complete/partial responses for all pts were observed in 1 pt/16 pts, respectively, for an overall RR of 31% (95% CI 20%–44%). Twenty-five pts (46%) had stable disease, and 11% had progression (6 pts were unevaluable.) No pathological complete responses were observed in 32 resected pts. After a median follow-up of 12 months, actuarial 1-year progression-free survival and overall survival (OS) are 54% and 79%, respectively. Median OS has not been reached. Conclusions: G/D is a well-tolerated preoperative regimen for pts with resectable NSCLC with activity rivaling platinum-based regimens. Further follow-up and additional studies comparing preoperative and adjuvant treatment are needed to assess the benefit of this regimen. [Table: see text]
Horizontal Transmission of Leukemia Virus and Leukemia in the Cat
Authors: William Jarrett, Oswald Jarrett, Lindsay Mackey, Helen Laird, William Hardy, Myron Essex
Journal: JNCI Journal of the National Cancer Institute (1973)

Neonatal and adult cats were exposed to cats that had been inoculated with feline leukemia virus (FeLV). A range of techniques was used on both sets of animals to monitor the presence or absence of virus, group-specific antigen, and antibodies to the virus and feline oncornavirus-associated cell membrane antigen (FOCMA). Horizontal transmission, occurring in most cases, took place between littermates when only a proportion was inoculated at birth and also when litters inoculated neonatally were housed, from birth, with unrelated litters. Adults became infected when exposed to cats that had been inoculated with FeLV as adults. Transfer of infection was demonstrable within a month of mixing; transmission of virus in this way could lead to the development of tumors in cats exposed as kittens or as adults. A wide variety of tissues was examined electron microscopically to determine possible routes of excretion of FeLV. Virus was most common in the trachea and oral mucosa, but it was also recovered from the urine and urinary bladder. Four adult cats became infected after being housed for 1 week with a cat with a naturally occurring alimentary lymphosarcoma.