tbuckley/cabot-search huggingface dataset:
Mouse Skin Tumor-Initiating Activity of 5-, 7-, and 12-Methyl- and Fluorine-Substituted Benz[&lt;italic&gt;a&lt;/italic&gt;]anthracenes&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: Alexander W. Wood, Wayne Levin, Richard L. Chang, Allan H. Conney, Thomas J. Slaga, Robert F. O'Malley, Melvin S. Newman, Donald R. Buhler, Donald M. Jerina
Journal: JNCI Journal of the National Cancer Institute (1982)

As an approach for elucidation of structure activity relationships that underlie the exceptionally large difference in carcinogenic activity between benz[a]anthracene and 7,12-dimethylbenz[a]anthracene (7,12-DMBA), 11 methyl- and/or fluorine-substituted benz[a]anthracenes were evaluated for tumor-initiating activity on mouse skin. Outbred CD-1 and outbred Sencar mice received a single topical application of the hydrocarbons followed by twice weekly applications of the tumor promoter 12-O-tetradecanoylphorbol 13-acetate for 16–26 weeks. 7,12-DMBA was almost two orders of magnitude more active as a tumor-initiator than 7- and 1 2-methylbenz[a]anthracene. Methyl substitution at the 7- and 7,12-positions of benz[a]anthracene was significantly more effective in the enhancement of tumorigenic activity than fluorine substitution at these positions. Although 7-fluorobenz[a]anthracene. 12-fluorobenz[a]anthracene, and 7,12-difluorobenz[a]anthracene had only 0.15, 0.26, and less than 0.005 times the tumor-initiating activity of their respective methyl-substituted derivatives, they were severalfold more active than benz[a]anthracene. 7-Fluorobenz[a]anthracene was slightly less active than 12-fluorobenz[a]anthracene, whereas 7-methylbenz[a]anthracene was about twofold more active than 12-methylbenz[a]anthracene. For 7,12-disubstituted benz[a]anthracenes, 7-methyl-12-fluorobenz[a]anthracene was more than twice as tumorigenic as 7-fluoro-12-methylbenz[a]anthracene, but each was individually more active than 7-methylbenz[a]anthracene and 12-methylbenz[a]anthracene, respectively. Both fluorinated compounds were much less active than 7,12-DMBA. Substitution of fluorine or methyl at the 5-position of 7-methylbenz[a]anthracene and substitution of fluorine at the 5-position of 12-methylbenz[a]anthracene dramatically reduced their tumorigenic activity.
Alzheimer's disease rarer among Nigerians than among African Americans
Authors: Deborah Josefson
Journal: BMJ (2001)

Rates of Alzheimer's disease are lower in Africans living in Africa than in African Americans, a recent study has reported ( JAMA 2001;285:739-47). The study is thought to be the first to find differences in the incidence of dementia related to Alzheimer's disease between an industrial and a non-industrialised country using identical researchers and methodologies.

The findings also suggested that environmental and cultural factors may have a role in the genesis of Alzheimer's disease. The longitudinal, prospective, population based study compared the incidence and prevalence of the disease in an elderly Nigerian population and an elderly African American population.

It was led by Dr Hugh Hendrie of the department of psychiatry and medicine at Indiana University …
Treatment of Metastatic Breast Cancer
Authors: William J. Gradishar
Journal: Journal of the National Comprehensive Cancer Network (2014)

Many newer agents in combination are being studied in the front-line treatment of women with HER2-positive metastatic breast cancer (MBC), but the story in the endocrine arena is more about the wise use of new strategies to overcome endocrine resistance, because no new antihormonal agents have been approved in the past decade. During his presentation at the NCCN 19th Annual Conference, Dr. William Gradishar explored what's new in the treatment of MBC, focusing primarily on enhancing the effect of endocrine therapy to overcome resistance with newer targeted agents such as everolimus, reevaluating the role of rebiopsy on disease progression and measuring circulating tumor cells as a surrogate of response to treatment, and reviewing the effective treatment regimens for HER2-positive disease.
Positron Emission Tomography for Evaluating Para-aortic Nodal Metastasis in Locally Advanced Cervical Cancer Before Surgical Staging: A Surgicopathologic Study
Authors: Peter G. Rose, Lee P. Adler, Michael Rodriguez, Peter F. Faulhaber, Fadi W. Abdul-Karim, Floro Miraldi
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Positron emission tomographic (PET) scanning provides a novel means of imaging malignancies. This prospective study was undertaken to evaluate PET scanning in detecting para-aortic nodal metastasis in patients with locally advanced cervical carcinoma and no evidence of extrapelvic disease before planned surgical staging lymphadenectomy. MATERIALS AND METHODS: After 20 mCi of 2-[ 18 F]fluoro-2-deoxy-d-glucose (FDG) were administered intravenously, the abdomen and pelvis were scanned. Continuous bladder irrigation was used to reduce artifact. Patients were classified by the presence or absence of FDG uptake in the primary tumor and in pelvic or para-aortic nodes. Para-aortic node metastases were classified as present or absent according to a standardized staging procedure. Pelvic node metastases were similarly classified in a subset of patients who underwent pelvic node resection. RESULTS: Thirty-two patients with stage IIB (n = 6), IIIB (n = 24), and IVA (n = 2) tumors were studied. Fluorodeoxyglucose was taken up by 91% of the cervical tumors. Six of eight patients with positive para-aortic node metastasis had PET scan evidence of para-aortic nodal metastasis. One of the two false-negatives had only one microscopic focus of metastatic cancer. In the para-aortic nodes, PET scanning had a sensitivity of 75%, a specificity of 92%, a positive predictive value of 75%, and a negative predictive value of 92%. Fluorodeoxyglucose para-aortic nodal uptake conferred a relative risk of 9.0 (95% confidence interval, 2.3 to 36.0) for para-aortic nodal metastasis. All 10 of 17 patients with metastasis were predicted by PET scanning (P &lt; .001); five of these patients had abnormalities on computed tomographic scans. CONCLUSION: Cervical cancers have a high avidity for FDG. The use of PET-FDG scanning accurately predicts both the presence and absence of pelvic and para-aortic nodal metastatic disease.
Prevalence of self-reported chronic respiratory symptoms and diseases among elderly people in communities located near gold mine tailings impoundments in South Africa
Authors: Vusumuzi Nkosi, Janine Wichmann, Gerard Hoek, Kuku Voyi
Journal: European Respiratory Journal (2014)

Communities in close proximity to mine dumps are perpetually exposed to toxic dust from mine dumps. Exposed are those in low socio-economic status, especially the elderly. To date no information is available regarding their health status in context to chronic respiratory symptoms and diseases. We investigated the association between proximity to mine dumps, other potential risk factors, chronic respiratory symptoms and diseases among elderly people in communities located near mine dumps using a respiratory-health questionnaire. 2397 elderly from exposed and non-exposed communities were cross-sectionally interviewed by locally trained field workers with a previously validated ATS-DLD-78 questionnaire obtained from British Medical Research Council (BMRC) for chronic respiratory symptoms and diseases. Communities near mine dumps had higher prevalence of self reported respiratory symptoms and diseases than those far away: chronic cough (75.3%), wheeze (48, 4%), asthma (17.3%), emphysema (5.6%), chronic bronchitis (13.4%), and emphysema (17.1). Residing in communities close to mine dumps, current smoking, ex-smoking, and occupational history in a dusty environment emerged as significant risk factor for chronic respiratory symptoms and diseases. Our study findings suggest that there is an epidemic of chronic respiratory symptoms and diseases among elderly in communities located near mine dumps  Keywords:Mine dumps; South Africa; Chronic respiratory diseases, elderly.
Patients with COPD wish to discuss palliative care with health professionals
Authors: Camilla Askov Mousing, Helle Timm, Marit Kirkevold, Kirsten Elisabeth Lomborg
Journal: European Respiratory Journal (2014)

Introduction: Patients with chronic obstructive pulmonary disease (COPD) may experience palliative care needs in early, late, and terminal phase of the disease. Health professionals experience several barriers in their work with identifying, initiating, and evaluating palliative interventions aimed at patients with COPD in primary care. Mayor barriers to a palliative care approach are the fear of destroying patients9 hopes and difficulties in deciding the right time to initiate discussions about palliative care.  Aim: To explore the preferences of home-living patients suffering from COPD in relation to conversations about palliative care needs and interventions.  Methods: In the period 2013-2014, twelve patients diagnosed with COPD were interviewed individually in their homes. The semi-structured interviews were conducted in three homecare districts in Denmark and were analyzed descriptively.  Results: Patients reported that they rarely initiated discussions about palliative interventions, as they would not bother the staff with their concerns. Unless they knew the staff very well, they would not open these serious conversations. Several patients explained that they did not discuss their worries with their immediate families either, as they would not cause concern. The analysis showed that patients worry about the future and they would like to discuss: the disease; worries about the future; and management of symptoms with health professionals.  Conclusion: Patients expressed that professionals should not be afraid to initiate conversations about palliative care. The patients knew that COPD was a serious illness and they did not fear that discussions about palliation could destroy their hopes for the future.
Occult Ovarian Tumors in Women With BRCA1 or BRCA2 Mutations Undergoing Prophylactic Oophorectomy
Authors: Karen H. Lu, Judy E. Garber, Daniel W. Cramer, William R. Welch, Jonathan Niloff, Deborah Schrag, Ross S. Berkowitz, Michael G. Muto
Journal: Journal of Clinical Oncology (2000)

To review the findings at prophylactic oophorectomy of a series of women who presented to a familial breast and ovarian cancer clinic.Data from medical charts, operative notes, and pathology reports were collected on women who had undergone prophylactic oophorectomies because of the elevated risk of ovarian cancer. Because only a subset of patients underwent BRCA1 and BRCA2 testing, each patient's risk of hereditary predisposition was calculated using the Berry-Parmigiani model and family history data.From June 1989 to December 1998, 50 women seen at our clinic underwent prophylactic oophorectomy, 33 of whom had a calculated risk of carrying a germline BRCA1 or BRCA2 mutation greater than 25%. Among this group, four incidental tumors were found (four of 33, or 12%); one tumor was noted at the time of surgery and three were noted only in the final pathology. Two patients had microscopic, poorly differentiated serous adenocarcinomas in multiple sites on both ovaries. A third patient had a bilateral serous borderline tumor with micropapillary features. The fourth patient had a microscopic serous borderline ovarian tumor. All four patients had germline BRCA1 or BRCA2 mutations, and three had unremarkable transvaginal ultrasonography examinations within 6 months before prophylactic surgery.Foci of malignant tumor are not uncommon in prophylactic oophorectomies performed in women at very high risk for ovarian cancer and may not be detected on ultrasonograms. Surgeons should have a high suspicion of finding cancer in these women at the time of prophylactic surgery, and careful pathologic assessment of the specimens should be conducted.
Changes in physical activity and sleep duration following hospitalisation with acute exacerbation of COPD
Authors: Dilber Yilmaz, James Dodd, Dinesh Shrikrishna, Nick Hopkinson, Paul Jones
Journal: European Respiratory Journal (2012)

Background: Exacerbations have a negative impact on physical activities in COPD patients, but little is known about their effect on sleep.

Aim: We investigated daily activities and length of sleep during and 3 months after hospitalisation for a COPD exacerbation.

Methods: We recruited 17 COPD patients immediately following a hospital admission for exacerbation (Acute) and 3 months after discharge (Recovered). Physical activity and sleep duration were measured using a multisensory armband (SenseWear Pro3) for 6 consecutive days. The average number of steps, duration lying, walking, sleep and resting were calculated per day. Physical activity level (PAL) was calculated by dividing total energy expenditure by resting energy expenditure. Step rate was calculated by dividing steps by walking time.

Results: The mean FEV1 at discharge was 39±14% pred. Activity levels are tabulated.

View this table:

Daily activity





Groups were compared using paired-t test. On recovery patients rested less, slept 55 mins longer (for 6hr 36min) and took more steps than in the acute state.

Conclusion: 3 months after hospitalisation COPD patients slept and exercised significantly more and rested less than when first discharged.
A therapeutic trial of decitabine and vorinostat in combination with chemotherapy for relapsed/refractory acute lymphoblastic leukemia
Authors: Michael J. Burke, Jatinder K. Lamba, Stanley Pounds, Xueyuan Cao, Yogita Ghodke‐Puranik, Bruce R. Lindgren, Brenda J. Weigel, Michael R. Verneris, Jeffrey S. Miller
Journal: American Journal of Hematology (2014)

DNA hypermethylation and histone deacetylation are pathways of leukemia resistance. We investigated the tolerability and efficacy of decitabine and vorinostat plus chemotherapy in relapse/refractory acute lymphoblastic leukemia (ALL). Decitabine (15 mg/m(2) iv) and vorinostat (230 mg/m(2) PO div BID) were given days 1-4 followed by vincristine, prednisone, PEG-asparaginase, and doxorubicin. Genome wide methylation profiles were performed in 8 matched patient bone marrow (BM) samples taken at day 0 and day 5 (postdecitabine). The median age was 16 (range, 3-54) years. All patients had a prior BM relapse, with five relapsing after allogeneic transplant. The most common nonhematological toxicities possibly related to decitabine or vorinostat were infection with neutropenia (grade 3; n = 4) and fever/neutropenia (grade 3, n = 4; grade 4, n = 1). Of the 13 eligible patients, four achieved complete remission without platelet recovery (CRp), two partial response (PR), one stable disease (SD), one progressive disease (PD), two deaths on study and three patients who did not have end of therapy disease evaluations for an overall response rate of 46.2% (CRp + PR). Following decitabine, significant genome-wide hypo-methylation was observed. Comparison of clinical responders with nonresponders identified methylation profiles of clinical and biological relevance. Decitabine and vorinostat followed by re-Induction chemotherapy was tolerable and demonstrated clinical benefit in relapsed patients with ALL. Methylation differences were identified between responders and nonresponders indicating interpatient variation, which could impact clinical outcome. This study was registered at www.clinicaltrials.gov as NCT00882206.
Investigations of Survival Properties of Airborne Murine Leukemia Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Edgar W. Larson, Gerard J. Spahn, Robert L. Peters, Robert J. Huebner
Journal: JNCI Journal of the National Cancer Institute (1970)

Aerosols of Rauscher leukemia virus were generated in a static cloud chamber conditioned at 75°F and 35% relative humidity to approximate the conditions found in animal colonies. Inactivation of the virus by sampling processes per se was minimal. A high proportion (over 99%) of the virus was inactivated, however, in the process of aerosolization and equilibration with the environment. Thereafter, the virus aerosols were relatively stable, decaying at approximately 1.0%/minute. These studies demonstrated the feasibility of applying conventional aerobiological techniques in the study of murine leukemia virus. Attempts to recover leukemia virus from air samples collected from infected animal colonies were unsuccessful.
Immunologic Control of a Retrovirus-Associated Murine Adenocarcinoma. VIII. &lt;italic&gt;Corynebacterium parvum&lt;/italic&gt;-Activated Natural Killer Cells as Potent Antibody-Dependent Cell-Mediated Cytotoxicity Effectors&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: K J Weinhold, D P Bolognesi, T J Matthews
Journal: JNCI Journal of the National Cancer Institute (1985)

The antibody-dependent lytic activity of Corynebacterium parvum-induced peritoneal exudate cells was examined in vitro by utilizing AD755a tumor targets and a homologous anti-AD755a hyperimmune serum. Maximum antibody-dependent cell-mediated cytolysis (ADCC) of tumor targets was achieved within 4 hours of incubation. ADCC activity was found primarily in the plastic nonadherent cell population and was greatly enriched following removal of phagocytic cells by carbonyl iron. Phenotypically, the cells active in short-term ADCC were Qa-5+, ASGM-1+, Thy 1.2+, and NK 1.1+ and were unaffected by treatment with Lyt 1.2, Lyt 2.2, MAC-1, or I-Ab antibodies plus complement. Cells active in antibody-independent lysis of AD755a targets were phenotypically identical to antibody-dependent effectors. Although indicative of a natural killer (NK) cell phenotype, C. parvum-induced effectors differed from "spontaneous" splenic NK cells in their relative sensitivity to anti-Thy 1.2 as well as to anti-NK 1.1 treatment. Unlike the IgG2a-dependent lysis of AD755a-derived cells by inflammatory macrophages, all IgG isotypes of antiAD755a serum were equally effective in ADCC mediated by C. parvum NK cells. Finally, treatment of C. parvum-inoculated animals with anti-ASGM-1 serum eliminated in vitro NK activity and abrogated the in vivo therapeutic effects of hyperimmune serum. These findings, together with other correlations detailed herein, strongly suggested that C. parvum-activated NK cells appeared to represent a unique subset of NK cells that can serve as potent effectors in the antibody-dependent killing of AD755a tumor cells.
Time to desaturation under 1 minute on the 6m walking test predicts chronic domiciliary oxygen therapy in COPD patients
Authors: Luisa Eiroa, Ruth Pitti, Juan Manuel Palmero, Juan Marco Figueira, Ana Isabel Velázquez, Magdalena Alonso, Jesús Rodríguez, Canelaria Ramos, Irene De Lorenzo, José Luis Trujillo, Alfonso Tauroni, Ignacio García Talavera
Journal: European Respiratory Journal (2011)

Introduction:  Time to desaturation (T90) on the 6 minute walking test (WT6m) on chronic obstructive pulmonary disease (COPD) patients correlates with time of desaturation during 24 hours oximetry. But it is unknown the clinical evolution in time of these patients.   Objetive:  To analise the gasometric parameters changes on copd patients with early desaturation on the WT6m 5 years later.   Material and Methods:  We studied 83 patients with COPD and desaturation on WT6m under 1 minute. 73 men/10 women, average 66 years old, Fev1: 42% pred and PO2 66mmHg. We did spirometries, gasometries, WT6m every 6 months for 5 years. The patients who during the study needed domiciliary oxygen theraphy, were prescribed by their phYsicians who did not know the content of the study.   Results:  5 years later, 65% of patients with early desaturation- T90 under 1 minute- had chronic domiciliary oxygen therapy vs 11% of patients with desaturation after 1 minute (T90 > 1 min), p   Conclusions:  Moderate-severe COPD patients desaturing before 1 min on the WT6m need oxygen therapy before 5 years opposed to patients with desaturation after 1 minute. Early desaturators need more clinical and gasometric controls.
Thymoma: Clinical features and prognostic factors in 47 patients
Authors: Natalija Samardzic, Dragana Jovanovic, Ljiljana Markovic Denic, Marina Roksandic Milenkovic, Vesna Ceriman, Marta Velinovic, Milija Gajic, Jelena Stojsic
Journal: European Respiratory Journal (2013)

Introduction: The purpose of this study was to investigate clinical aspects of Thymoma in our population.  Matherial and methods: We retrospectively reviewed medical records of 47 patients (pts) with Thymoma who were diagnosed and treated in our hospital from 1993 to 2009. There were 22 male and 25 female patients, with ratio 1:1,1.  Results: For the age distribution only 7(15%) pts were younger than 40 yrs. Asymptomatic pts were 17(36%). The most frequent symptoms were chest pain and malaise (53%) each, cough (47%), dysphagio(20%), dispnea (13%) and hemoptysis (7%). Myasthenia gravis was the most common paraneoplastic Sy (17%). The radiographic findings were abnormal in all pts. More than half of the pts were in the early (I) stage of disease (52%); the most common histopathological finding was cortical Thymoma (45%). Complete resection was obtained in 83% of patients with a mean survival of 5.6 yrs. From 1993 to 2003, 19(40%) patients underwent surgical resection of a thymoma. Overall 5-, 10-yr survival rates were 74% and 63%, respectively, with the first stage of the disease in 63% of cases.  Conclusion: Long-term survival can be obtained when a complete resection is performed. Also, pathological classification is a major prognostic factor. Our data are corresponding with worldwide.  References:  1. Davenport E, Malthaner RA. The role of surgery in the management of thymoma; a systemic review. Ann Thorac. Surg 2008; 86: 673.  2. Kim DJ, Yang WI, Choi SS et al. Prognostic and clinical relevance of the world health organisation schema for the classification of thymic epitheliale tumors: a clinicopathologic study of 108 patients and literature review. Chest 2005; 127: 755.