tbuckley/cabot-search huggingface dataset:
Preirradiation chemotherapy with carboplatin and etoposide in newly diagnosed embryonal pediatric CNS tumors.
Authors: R L Heideman, E H Kovnar, S J Kellie, E C Douglass, A J Gajjar, A W Walter, J A Langston, J J Jenkins, Y Li, C Greenwald
Journal: Journal of Clinical Oncology (1995)

PURPOSE We evaluated the clinical efficacy of preirradiation carboplatin (CARBO) and etoposide (VP-16) in 25 patients with newly diagnosed embryonal CNS tumors. PATIENTS AND METHODS Sixteen patients with high-risk medulloblastoma and nine with other embryonal tumors were treated with two daily doses of CARBO 350 mg/m2 and VP-16 100 mg/m2 (CARBO/VP) every 21 days for four cycles before standard craniospinal irradiation. Patients with disease progression (PD) before radiation therapy were additionally treated with intensive postirradiation cyclophosphamide (CYCLO) and vincristine (VINC). RESULTS Among 23 assessable patients, 48% (95% confidence interval, 27% to 69%) had a complete response (CR) or partial response (PR) to CARBO/VP; eight had PD. Among the subgroup of 15 assessable patients with medulloblastoma, 53% had a CR or PR (95% confidence interval, 27% to 79%) and five PD. The toxicity of CARBO/VP was predominantly hematologic; although grade IV neutropenia was common, only five episodes of febrile neutropenia occurred. Only thrombocytopenia was a more common toxicity than in other reported chemotherapy regimens; ototoxicity was less common than in cisplatin (CDDP) regimens. CONCLUSION The responses and survival associated with neoadjuvant CARBO/VP are similar to those with CDDP-containing and other neoadjuvant drug regimens. Although the rate of progression with this regimen may be higher than with similar CDDP-containing regimens, the numbers of patients in other published studies of these agents are too small to detect meaningful statistical differences. Future studies must balance the apparently comparable efficacy of CARBO and CDDP with their differing toxicities.
The prevalence of neoplastic transformation in idiopathic pulmonary fibrosis (IPF) lungs. A report from a transplanted IPF population
Authors: Elisabetta Balestro, Emanuela Rossi, Francesca Lunardi, Nazarena Nannini, Monica Loy, Federico Rea, Marina Saettta, Fiorella Calabrese
Journal: European Respiratory Journal (2011)

Idiopathic pulmonary fibrosis (IPF) is known to be associated with increased risk of lung cancer but the potential pathological abnormalities that could precede the development of lung cancer are not well known. The aim of our study was to investigate the prevalence of high grade dysplasia/foci of neoplastic transformation (precancerous changes) and their relationship with metaplastic changes in honeycomb areas.  The lungs of 66 patients who underwent lung transplantation for IPF were studied. Scores were used to quantitate the degree of honeycomb changes and squamous, cuboidal and bronchial cell metaplasia in honeycombed areas. The presence or absence of precancerous changes in the same areas was recorded. Twelve of the 66 patients (18%) showed foci of neoplastic transformation/high grade dysplasia (“cancer” group). The “cancer” group (mean age at transplant 53±9 years; F:M=3:9) had similar smoking history, age and duration of disease than the “no cancer” group (mean age at transplant 57±6 years; F:M=17:37). Although all lungs showed metaplasia, the score of squamous (p=0.0001), cuboidal (p=0.018) and bronchial cell (0.018) metaplasia was significantly higher in the “cancer” than in the “no cancer”, while the honeycomb score was similar in the two groups.  In conclusion, contrary to previous reports, we have found that the presence of metaplasia, specially squamous, in the honeycombed areas, is associated to the development of precancerous changes in IPF, independently to smoking history.
Absence of favourable changes in circulating levels of interleukin-16 or β-chemokine concentration following structured intermittent interruption treatment of chronic human immunodeficiency virus infection
Authors: M. Montes de Oca Arjona, R. Pérez Cano, M.J. Orozco, A. Martín Aspas, F. Guerrero, C. Fernández Gutiérrez del Álamo, J.A. Girón-González
Journal: Clinical Microbiology and Infection (2005)
Combination study of tiotropium and olodaterol in human precision-cut lung slices
Authors: Marco Schlepütz, Nina Maihöfer, Annette D. Rieg, Saskia Westphal, Alberto Perez-Bouza, Till Braunschweig, Thomas Schröder, Jan W. Spillner, Rüdiger Autschbach, Michael P. Pieper, Stefan Uhlig, Christian Martin
Journal: European Respiratory Journal (2013)

In COPD, monotherapy often fails to improve health status. Hence, combinations of bronchodilators are recommended. The pharmacological impact of drugs on bronchoconstriction (BC) can be determined  in vitro  by precision-cut lung slices (PCLS). So, the present aim was to characterize the combined effect of tiotropium and the novel LABA olodaterol on BC in human lung tissue.  PCLS were prepared from lung lobes received from cancer patients. BC in PCLS was monitored by videomicroscopy. First, concentration-response curves with carbachol (CCh, 10 -8 –10 -3 M) were performed in the presence and absence of tiotropium (10 -11 -10 -8 M) or olodaterol (10 -10 –10 -7 M). For the combined effect of tiotropium and olodaterol, concentration-response curves with CCh were conducted at 10 -9.5 M tiotropium or 10 -9 M olodaterol alone and in their combination.  Tiotropium concentration-dependently inhibited CCh-induced BC and a suitable inhibitory concentration for the combination study was found at 10 -9.5 M. The functional antagonist olodaterol also inhibited CCh-induced BC and an appropriate inhibitory concentration for the combination study was determined to 10 -9 M. In the combination study half-maximal effective concentrations (logEC 50 ) for CCh-induced BC were -5.9±0.2 under control conditions, -5.7±0.1 at 10 -9.5 M tiotropium, -5.4±0.2 at 10 -9 M olodaterol and -4.6±0.2 for the combination of tiotropium and olodaterol.   In vitro  the combination of tiotropium and olodaterol was more effective to inhibit BC than each bronchodilator alone. Since those studies were performed in human tissue, correlation to the  in vivo  situation may be allowed and the combination of tiotropium and olodaterol may be beneficial in the treatment of patients.
Additional therapy of COPD patients with respiratory muscles dysfunction
Authors: Yuliia Huba, Olena Myronenko
Journal: European Respiratory Journal (2014)

Dihydropyridine calcium antagonists (CA), primarily act on smooth muscles of arteries, i.e. are typical peripheral vasodilators, reducing the pressure in the pulmonary artery. CA also able to reduce the synthesis of matrix metalloproteinase (MMP). One of the positive effects realized through positive employmenton the respiratory muscles (RM).

The aim of the study was to evaluate effect of different therapy for COPD pts with RM dysfunction.

Material. COPD patients with II stage were divided in to 4 groups:1st (berodual 2 puff 3 times per day) - 12 pts, 2nd (tiotropium 18 μg once daily) – 14 pts, 3d (formoteroly fumarat 12 μg twice daily) – 10 pts, 4th (berodual+amlodipini 5 mg) – 16 pts.

Methods. Spirometry and pneumotonometry were performed by means MasterScreen Body/Diff (“Jaeger”, German). FEV1, PImax, PEmax and P0.1 were evaluated.

Results. No significant differences in the level of FEV1, PEmax and P0.1 in groups of observations were observed either at baseline or at the end of treatment. Changes of PImax was determined as provide marker of RM dysfunction for COPD pts. Significant increase of PImax has been established in all groups, determination of growth was conducted using a paired Wilcoxon test (p<0,05).

![Figure][1] 



Conclusion. The most considerable improvement of inspiratory muscles strength was revealed in the group treated with amlodipini besilat. But therapy with LABA is demonstrate very good effect on level of PImax.

 [1]: pending:yes
Combination chemotherapy versus single agents followed by combination chemotherapy in stage IV non-small-cell lung cancer: a study of the Eastern Cooperative Oncology Group.
Authors: P D Bonomi, D M Finkelstein, J C Ruckdeschel, R H Blum, M D Green, B Mason, R Hahn, D C Tormey, J Harris, R Comis
Journal: Journal of Clinical Oncology (1989)

During the last decade, the Eastern Cooperative Oncology Group (ECOG) has studied a series of combination chemotherapy regimens in metastatic (stage IV) non-small-cell lung cancer (NSCLC). In January 1984, the ECOG activated a randomized study, EST 1583, which concluded the evaluation of combination regimens in phase III trials and initiated the evaluation of single agents exclusively in previously untreated patients. The treatment regimens in EST 1583 consisted of: (1) mitomycin, vinblastine, and cisplatin (MVP); (2) vinblastine and cisplatin (VP); (3) MVP alternating with the regimen cyclophosphamide, doxorubicin, methotrexate, and procarbazine (CAMP); (4) carboplatin followed by the MVP regimen at the time of progression; and (5) iproplatin followed by MVP at the time of progression. From January 1984 to July 1985, 743 patients were entered on this trial and 699 fulfilled the eligibility requirements. The following objective response rates (complete plus partial remissions) were observed: first-line MVP, 20%; VP, 13%; MVP/CAMP, 13%; carboplatin, 9%; iproplatin, 6%; and second-line MVP, 6%. First-line MVP produced a significantly higher response rate than the other treatments (P = .03) adjusted for prognostic variables. Using analyses that were adjusted for prognostic covariates, survival for patients treated on a given regimen was compared with survival for all remaining patients. These analyses showed that treatment with carboplatin was associated with longer survival (median survival time, 31.7 weeks; P = .008) while initial treatment with MVP was associated with a trend for shorter survival (median survival time, 22.7 weeks; P = .09). It should be noted that none of these regimens appear to have produced a clinically meaningful prolongation of survival. Similar analyses evaluating time to progression disclosed that carboplatin-treated patients had a significantly longer time to progression (median time to progression, 29 weeks) than all remaining patients (P = .01). Life-threatening and lethal toxicities (toxicity grades 4 and 5) were greater on the combination regimens than on the single agents (P less than .0001). Based on these results, current group-wide ECOG trials in stage IV NSCLC consist of randomized phase II trials evaluating single agents.
Abstract 2209: The Use of the Magnetic Navigation System Allows Shorter Procedure Times and a Reduction of Radiation Risk in Small Children Undergoing Catheter Ablation
Authors: Tamas Szili-Torok, Bruno Schwagten, Maarten Witsenburg, Natasja de Groot, Luc Jordaens
Journal: Circulation (2009)

Background: Transcatheter ablation is an effective method to eliminate arrhythmia substrates in symptomatic children with various types of arrhythmias. Unfortunately, in small-sized children only a...
Dopamine Regulation of Amygdala Inhibitory Circuits for Expression of Learned Fear
Authors: Oh-Bin Kwon, Joo Han Lee, Hyun Jin Kim, Seungho Lee, Sanghyeon Lee, Min-Jae Jeong, Su-Jeong Kim, Hee-Jung Jo, Bumjin Ko, Sunghoe Chang, Sang Ki Park, Yun-Beom Choi, Craig H. Bailey, Eric R. Kandel, Joung-Hun Kim
Journal: Neuron (2015)
Pneumatocoeles that required surgery in childhood: Report of 2 cases
Authors: V. Rozalia, Dimos Gidaris, Fotios Maris, Sofia Ioannidou, Dimitra Tzavella
Journal: European Respiratory Journal (2012)

Pneumatocoeles are thin-walled filled with air cystic lesions that have been recognized as a potential complication of pneumonia. Although, they are usually asymptomatic, they may enlarge and compress the adjacent lung and mediastinum.  The aim of this report is to describe 2 cases of severe pneumonia complicated by pneumatocoeles that required surgical intervention.  Case 1  A one year old girl presented with a 2 day history of pyrexia. Radiological investigation revealed a right sided consolidation with pleural effusion. Pleural fluid culture revealed staphylococcus aureus. Antibiotic treatment and drainage failed and a CT scan on day 21 revealed an enlarging pneumatocoele on the right causing mediastinal shift. The child developed acute respiratory failure; Successful decompression of the pneumatocoele was achieved after initial urgent needle aspiration. Radiologic resolution was complete 2 months post initial presentation.  Case 2  A previously healthy 8 month old boy was admitted to our institution with a tension pneumatocoele following a severe necrotic pneumonia. Blood culture was positive for Pneumococcus type 3F. On auscultation there was dramatically decreased air entry on the left side. CXR and CT revealed hyperinflation,large air cyst causing mediastinal shift to the right. Conservative management was initially attempted, but when o-=xygen saturation decreased dramatically surgical excision (pneumonectomy) was decided. The patient is now asymptomatic 2 months post discharge  Conclusion  Tension pneumatocoeles, although rare, are a serious complication of pneumonia that may need surgical intervention when the patient is in critical condition.
Effects of radiation and chemotherapy on cognitive function in patients with high-grade glioma.
Authors: B V Taylor, J C Buckner, T L Cascino, J R O'Fallon, P L Schaefer, R P Dinapoli, P Schomberg
Journal: Journal of Clinical Oncology (1998)

PURPOSE The effect of radiotherapy on the long-term cognitive performance of patients treated for intracranial neoplasm is a major concern to clinicians and patients, particularly as long-term survival or cure is possible for a small minority of patients. To assess the effects of cranial radiotherapy and chemotherapy on the cognitive performance of high-grade glioma patients, we analyzed cognitive performance data collected in a series of prospective clinical trials. METHODS We studied 701 high-grade brain tumor patients entered onto two consecutive North Central Cancer Treatment Group (NCCTG) randomized treatment trials designed to compare radiotherapy and carmustine (BCNU) versus radiotherapy and 1-(2-chloroethyl)-3(2,6 dioxo-l-piperidyl)-1-nitrosource a (PCNU) (first trial) and radiotherapy and BCNU and interferon alfa (IFN) versus radiotherapy and BCNU (second trial). Folstein Mini-Mental Status Exam (MMSE) score and Eastern Cooperative Oncology Group (ECOG) performance score (PS) recorded at baseline and 6, 12, 18, and 24 months were analyzed to assess cognitive and physical function over time. Patients who did not demonstrate tumor progression within 60 days of the assessment time were considered nonprogressors at that evaluation. A loss of greater than 3 points on the MMSE was considered significant deterioration. RESULTS The number of patients who experienced a greater than 3-point decrease in MMSE from baseline was 13 of 119 nonprogressors (10.9%; 95% confidence interval [CI], 6.3% to 18.9%) at 6 months, three of 54 nonprogressors (5.5%; 95% CI, 0.5% to 12.8%) at 12 months, three of 30 nonprogressors (10%; 95% CI, 2.1% to 26.5%) at 18 months, and four of 22 nonprogressors (18.2%; 95% CI, 5.2% to 40.3%) at 24 months. The CIs at all times overlapped, which indicates no statistically significant increase in the percentage of patients who experienced a significant decrease in their MMSE score. Patients who demonstrated a significant decrease in their MMSE score were significantly older than those who did not (P = .0017) at 6 months and remained so throughout follow-up; moreover, they had a significantly shorter time to progression and death. ECOG PS was strongly negatively correlated with MMSE score throughout the study, and MMSE score at all time intervals was correlated with baseline PS. CONCLUSION In this population of glioma patients who received radiotherapy, there is no clear trend to cognitive worsening. Factors such as older age, poorer PS, and subclinical tumor progression may be more significant factors in those patients who did demonstrate a significant cognitive decline.
Decoding Alzheimer’s in the age of genome-wide analyses
Authors: Rudolph E Tanzi
Journal: Molecular Neurodegeneration (2013)

Alzheimer’s disease (AD) is strongly influenced by genetic factors as evidenced by numerous family and twin studies. Over the past two decades, others and we have co-discovered three early-onset familial AD genes, APP, PSEN1, and PSEN2, which can carry any of >200 fully penetrant mutations characterized by mendelian inheritance. For late-onset AD, the most prevalent and highest impact risk factor is the epsilon 4 variant of APOE, which increases risk by 3.7-fold in the heterozygous state and >10-fold when two copies are inherited. As part of our Alzheimer’s Genome Project funded by the Cure Alzheimer’s Fund and the NIMH, we have been identifying novel AD candidate genes. In Bertram et al. (2008), we reported genome-wide association of AD with several loci including the spinocerebellar ataxia 1 gene, ATXN1, and the SIGLEC3 gene, CD33. Functional studies of the ATXN1 gene carried out both in vitro and in vivo in ATXN1 knockout mice show that ATXN1 can regulate Aβ levels via modulation of β-secretase. CD33 is just one of several genes (TREM2, CR1, etc) involved in the innate immune system of the brain that have been associated with AD risk. In addition, we discovered association of AD with ADAM10, which encodes the major α-secretase in the brain. Re-sequencing of this gene in the best associated AD families led to two rare mutations that tightly co-segregated with AD in seven (of 1000) AD families screened, all with average age of onset ~70 years. We have shown both mutations to impair ADAM10 non-amyloidogenic cleavage of APP in vitro and in transgenic mice, including double trangenics with AD (tg2576) mice. Thus, these are the first rare, highly penetrant mutations reported for late-onset AD. We have also carried out genome-wide association studies on >800 well-characterized late-onset AD families (NIMH and NIA-LOAD samples) using Affymetrix genotyping arrays containing either one million (6.0) or 20,000 coding SNPs. More recently, we have performed whole genome sequencing (Illumina, Hiseq) on over 1500 samples from AD families/sibships. The elucidation of the genes and functional variants influencing risk for AD should continue to enhance our understanding of AD etiology and pathogenesis. Ultimately, these genes will be used to predict risk for AD and guide novel the development of therapies for the effective treatment and prevention of this terrible disease.
A prospective, cohort, multicentre study of candidaemia in hospitalized adult patients with haematological malignancies
Authors: M.N. Gamaletsou, T.J. Walsh, T. Zaoutis, M. Pagoni, M. Kotsopoulou, M. Voulgarelis, P. Panayiotidis, T. Vassilakopoulos, M.K. Angelopoulou, M. Marangos, A. Spyridonidis, D. Kofteridis, A. Pouli, D. Sotiropoulos, P. Matsouka, A. Argyropoulou, S. Perloretzou, K. Leckerman, A. Manaka, P. Oikonomopoulos, G. Daikos, G. Petrikkos, N.V. Sipsas
Journal: Clinical Microbiology and Infection (2013)
Tumor Control by Irradiation: A C3H/He Mouse Mammary Carcinoma in Mammary-Tumor-Agent-Positive and Mammary-Tumor-Agent-Free Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Herman Suit, Andrija Kastelan
Journal: JNCI Journal of the National Cancer Institute (1968)

Tumor control assays have been described for studies of a C3H/He mouse mammary carcinoma transplanted into C3H/He (C3H/He × C57BL)F1(C3BF1), or (C57BL ×C3H/He)F1(BC3F1)animals. All irradiations were performed under conditions of local tissue hypoxia and at a tumor volume of 250 mm3. The TCD50 was the same for tumor growing in each of the three animal systems listed. Further, active immunization of the BC3F1mice, by having tumor transplanted into the right thigh and then cured by local irradiation, did not affect the TCD50. Nor was the TCD50 modified by an active immunization procedure begun 21 days after application of local irradiation. Thus, in this animal tumor system, a very weak but readily demonstrable antigenicity of the tumor cells did not modify the tumor control probability after local irradiation of tumor.
The Epidemiology of Sarcomas of the Uterus
Authors: Bernard L. Harlow, Noel S. Weiss, Steven Lofton
Journal: JNCI Journal of the National Cancer Institute (1986)

Data from nine population-based cancer registries (1973-81) were analyzed to examine the demographic characteristics that are related to the occurrence of sarcomas of the uterus. Leiomyosarcoma and mixed mesodermal sarcoma accounted for 86% of 1,452 uterine sarcomas reported, and both were more common in black women than in white women. The incidence of mixed mesodermal sarcoma was low through middle age, after which it rose sharply. The incidence of uterine leiomyosarcoma, however, was highest in middle-aged women and declined thereafter. The age-incidence pattern of uterine leiomyosarcoma resembles that of carcinomas of the female reproductive tract, unlike the pattern of other uterine sarcomas or sarcomas occurring elsewhere. This suggests that one or more factors that play a role in the etiology of carcinomas of the reproductive tract may be involved in the etiology of this tumor as well.
The association between metabolic factors and asthma in adolescents of southern Taiwan
Authors: Tsu-Nai Wang, Tsu-Yu Yuan, Li-Yu Wang
Journal: European Respiratory Journal (2012)

Background : The prevalence of asthma has increased distinctly over the last two decades. Arising prevalence of metabolic syndrome has also been observed. Few studies have discussed the relation between metabolic factors and asthma.   Objective : This study aimed to assess whether there is an association with asthma and metabolic factors.   Methods : The cross-sectional study randomly sampled 7583 subjects ≤ 18 years old from elementary, junior and senior high schools in southern Taiwan. There were 5754 eligible subjects in the ultimate analysis because they completed a questionnaire interview, anthropometric measurements and blood samples collection. Furthermore, we conducted a meta-analysis including 13 studies according to criteria to review the association with asthma, BMI and total cholesterol (TC).   Results : We found a significant association between asthma and abdominal fat (aOR=4.34, p=0.009) and high concentrations of cholesterol (aOR=1.93, p   Conclusion : We did not measure high density cholesterol [HDL] and low density cholesterol [LDL]. Therefore, we cannot determine the relationship between disease and cholesterol was resulted from HDL or LDL. Asthma patients are more obese, have higher concentrations of cholesterol and more metabolic factors.