tbuckley/cabot-search huggingface dataset:
Acute exposure to swine dust causes bronchial hyperresponsiveness in healthy subjects
Authors: P Malmberg, K Larsson
Journal: European Respiratory Journal (1993)

Six urban subjects, with little or no previous experience of farm-work, were exposed to dust while weighing swine for 2-5 h. Three subjects experienced toxic symptoms 4-5 h after the beginning of exposure. Bronchial responsiveness increased in all subjects within 6 h (more than three doubling steps difference in a methacholine test). One week later, airway responsiveness had partly normalized. The mean (interquartile range) cumulative dose of methacholine causing a 20% decrease in forced expiratory volume in one second (FEV1) was 3.1 (1.0-6.6) mg, before exposure, fell to 0.13 (0.01-0.76) mg 6 h after exposure (p < 0.02), and was 0.99 (0.42-1.5) mg one week later (n = 5, p < 0.05), Mean (SD) FEV1 decreased 5 (2)%. The concentration of total dust varied between 9 and 14 mg.m-3 and of endotoxin between 0.1 and 0.5 mu g.m-3. Thus inhalation of swine farm dust, caused a marked increase in bronchial responsiveness in non-sensitized subjects.
Is lobular breast cancer mainly inherited from the father?
Authors: H. L. Olsson, C. Ellberg
Journal: Journal of Clinical Oncology (2010)

1544 Background: The association between invasive lobular carcinoma (ILC) and family history is not clear, some studies show no association; however, a few studies made on younger women show an association to family history, especially in BRCA2 carriers. Therefore, we thought it would be interesting to investigate the relationship between histopathological subtype of breast cancer, focusing on lobular breast cancer, and cancer other than breast cancer in first degree relatives to possibly find new hereditary patterns predisposing for cancer. We also excluded male breast cancer. Methods: In 1677 consecutive breast cancer patients the following risk factors were related to histopathology; parity, HRT use and detailed family history of breast cancer. All analyses were age adjusted and factors were simultaneously adjusted for. Results: In binary regression logistic models adjusted for age at diagnosis, type of breast cancer inheritance, HRT use and number of children, the patients with ILC were found to be significantly associated to having a father diagnosed with cancer, OR 1.72 (CI 1.13-2.61), no association with a mother diagnosed with cancer. The most prevalent cancer diagnosis was prostate cancer, however, in comparison with the other histopathologies sarcoma and leukemia occurred more often. There was a significant association between ILC and prostate cancer OR 2.4 (CI 1.1-5.3), and the association was stronger in the younger patient group OR 2.9 (CI 1.1- 7.8), and weaker in the older group OR 1.9 (CI 0.5-7.4). The association between ILC and a father remained significant after excluding prostate cancer OR 1.94 (CI 1.20-3.14). Conclusions: Among patients with ILC there was an overrepresentation of having a father diagnosed with cancer (24%) in comparison with mothers (13%). In line with previous findings (Loman et al. 2003), an association between ILC and prostate cancer was found. The association with a father diagnosed with cancer remained significant even after removing prostate cancer, indicating that this phenomenon was not associated to prostate cancer exclusively. We are presently investigating if gender differences in risk may be due to an effect of sex on risk alleles by imprinting. No significant financial relationships to disclose.
2-Chlorodeoxyadenosine activity in patients with untreated chronic lymphocytic leukemia.
Authors: A Saven, R H Lemon, M Kosty, E Beutler, L D Piro
Journal: Journal of Clinical Oncology (1995)

2-chlorodeoxyadenosine (2-CdA; cladribine) is a purine analog with activity in patients with chronic lymphocytic leukemia (CLL) who fail to respond to alkylator therapy. We conducted a phase II trial of 2-CdA in previously untreated CLL patients.2-CdA was administered to 20 patients with previously untreated CLL as a 0.1-mg/kg/d 7-day continuous intravenous infusion every 28 to 35 days until maximum response or prohibitive toxicity.A median of four courses (range, one to nine) was administered to each patient. Five patients (25%) achieved a complete response and 12 (60%) achieved a partial response, for an overall response rate of 85%. The median response follow-up duration was 8+ months (range, 3 to 27). Myelosuppression was the principal toxicity. Four of 20 patients (20%) experienced grade III or IV thrombocytopenia. Three patients, all of whom received corticosteroid therapy, developed opportunistic infections at a median of 19 months following discontinuation of 2-CdA therapy.2-CdA has major activity in patients with previously untreated CLL, and the lower response rates seen in previously treated patients may be due in part to poor marrow reserve from prior therapy. Determination of the relative effectiveness of 2-CdA, fludarabine, and chlorambucil in the treatment of CLL patients will require a randomized trial.
Sequences of topotecan and cisplatin: phase I, pharmacologic, and in vitro studies to examine sequence dependence.
Authors: E K Rowinsky, S H Kaufmann, S D Baker, L B Grochow, T L Chen, D Peereboom, M K Bowling, S E Sartorius, D S Ettinger, A A Forastiere, R C Donehower
Journal: Journal of Clinical Oncology (1996)

PURPOSE A phase I and pharmacologic study was performed to evaluate the feasibility of administering the topoisomerase I (topo I) inhibitor topotecan (TPT) in combination with cisplatin (CDDP) in minimally pretreated adults with solid tumors. The study was designed to evaluate the magnitude of the toxicologic and pharmacologic differences between the two sequences of drug administration. MATERIALS AND METHODS TPT was administered as a 30-minute infusion daily for 5 days and CDDP was given either before TPT on day 1 or after TPT on day 5. Each patient was treated with both schedules on an alternating basis every 3 weeks. Sequential dose escalation of TPT or CDDP resulted in three dosage permutation of TPT/CDDP (mg/m2): 0.75/50, 1/50, and 0.75/75. After the maximum-tolerated dose (MTD) level was achieved, the feasibility of using granulocyte colony-stimulating factor (G-CSF) to permit further dose escalation was studied. To examine the interaction of TPT and CDDP in vitro, human A549 lung cancer cells were exposed to these agents concurrently and sequentially. RESULTS Dose-limiting neutropenia and thrombocytopenia resulted after the doses of TPT or CDDP were increased to greater than 0.75 and 50 mg/m2, respectively, without and with G-CSF. The sequence of CDDP before TPT induced significantly worse neutropenia and thrombocytopenia than the alternate sequence. In vitro studies failed to provide any evidence for the differences in the cytotoxicity of these two sequences. Instead, pharmacokinetic studies suggested that the differences in toxicity were due, in part, to lower TPT clearance and exposure when CDDP preceeds TPT, possibly due to subclinical renal tubular toxicity induced by CDDP. CONCLUSION The sequence of CDDP before TPT at doses of 50 and 0.75 mg/m2, respectively, is recommended for subsequent clinical trials in tumor types in which both agents have significant single-agent activity. The potential for sequence-dependent cytotoxic, toxicologic, and pharmacologic effects should be evaluated in concurrent clinical and laboratory studies in the course of developing combination chemotherapy regimens that consist of topo I-targeting agents and other antineoplastic agents, particularly DNA-damaging agents.
Abstract 19118: Motor and Cognitive Impairment Following Pediatric Heart Transplantation in the US Analysis of Organ Procurement and Transplant Network Data
Authors: Leslie B Smoot, Christina VanderPluym, Kimberlee Gauvreau, Melisa Oliva, TP Singh, Christopher Almond
Journal: Circulation (2012)

BACKGROUND: Studies suggest the cognitive and motor performance of pediatric heart transplant (HT) recipients falls below population norms; though the incidence and risk factors for these observations are not well characterized. We sought to identify independent predictors of cognitive and motor impairment after HT based on predictors recorded at the time of HT. METHODS: OPTN data were used to identify all children <18 years of age with a post-HT neurodevelopmental screen available between 2007 and 2010, when the screen was mandatory for all children. Logistic regression was used to identify independent risk factors for definite or probable cognitive and motor impairment, respectively, as reported by transplant centers using a standardized screen. RESULTS: Of 1999 children with a cognitive screen available and 2048 children with a motor screen available, the median age at HT was 6 years, the median weight was 19.1 kg, 57% were white, 37% had congenital heart disease (CHD), 59% were listed UNOS status 1A a...
The Impact of the US Food and Drug Administration Chlorofluorocarbon Ban on Out-of-pocket Costs and Use of Albuterol Inhalers Among Individuals With Asthma
Authors: Anupam B. Jena, Oliver Ho, Dana P. Goldman, Pinar Karaca-Mandic
Journal: JAMA Internal Medicine (2015)

The US Clean Air Act prohibits use of nonessential ozone-depleting substances. In 2005, the US Food and Drug Administration announced the ban of chlorofluorocarbon (CFC) albuterol inhalers by December 31, 2008. The policy resulted in the controversial replacement of generic CFC inhalers by more expensive, branded hydrofluoroalkane inhalers. The policy's impact on out-of-pocket costs and utilization of albuterol is unknown.To study the impact of the US Food and Drug Administration's CFC ban on out-of-pocket costs and utilization of albuterol inhalers.Using private insurance data from January 1, 2004, to December 31, 2010, we investigated the effect of the CFC ban on out-of-pocket costs and utilization of albuterol inhalers among individuals with asthma (109,428 adults; 37,281 children), as well as asthma-related hospitalizations, emergency department visits, and outpatient visits. We estimated multivariable models adjusted for age, sex, comorbidities, and mean out-of-pocket costs of albuterol inhalers in an individual's drug plan. We analyzed whether effects varied between adults vs children and those with persistent vs nonpersistent asthma.Pharmacy claims for albuterol inhalers, as well as asthma-related hospitalizations, emergency department visits, and outpatient visits.The mean out-of-pocket albuterol cost rose from $13.60 (95% CI, $13.40-$13.70) per prescription in 2004 to $25.00 (95% CI, $24.80-$25.20) immediately after the 2008 ban. By the end of 2010, costs had lowered to $21.00 (95% CI, $20.80-$21.20) per prescription. Overall albuterol inhaler use steadily declined from 2004 to 2010. Steep declines in use of generic CFC inhalers occurred after the fourth quarter of 2006 and were almost fully offset by increases in use of hydrofluoroalkane inhalers. In multivariable analyses, a $10 increase in out-of-pocket albuterol prescription costs was estimated to lower utilization by 0.92 percentage points (95% CI, -1.39 to -0.44; P < .001) for adults and 0.54 percentage points (95% CI, -0.84 to -0.24; P = .001) for children, with no difference between adults vs children and patients with persistent vs nonpersistent asthma and with no impact on asthma-related hospitalizations, emergency department visits, and outpatient visits.The Federal ban of CFC inhalers led to large relative increases in out-of-pocket albuterol costs among privately insured individuals with asthma and modest declines in utilization. The policy's impact on individuals without insurance, who faced greater cost increases, is unknown.
Relationships of Tubal Ligation to Endometrial Carcinoma Stage and Mortality in the NRG Oncology/Gynecologic Oncology Group 210 Trial
Authors: Ashley S. Felix, Louise A. Brinton, D. Scott McMeekin, William T. Creasman, David Mutch, David E. Cohn, Joan L. Walker, Richard G. Moore, Levi S. Downs, Robert A. Soslow, Richard Zaino, Mark E. Sherman
Journal: JNCI Journal of the National Cancer Institute (2015)

Stage is a critical determinant of treatment among endometrial carcinoma patients; understanding patterns of tumor spread may suggest approaches to improve staging. Specifically, the importance of exfoliation of endometrial carcinoma cells through the fallopian tubes into the peritoneum is ill defined. We assessed the hypothesis that tubal ligation (TL), which should impede transtubal passage of cells, is associated with lower endometrial carcinoma stage at presentation and, consequently, lower mortality. The NRG Oncology/Gynecologic Oncology Group (GOG) 210 Trial included 4489 endometrial carcinoma patients who completed a risk factor questionnaire that included TL history. Pathology data were derived from clinical reports and central review. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between TL with stage and peritoneal metastasis, overall and by tumor subtype. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals for TL and mortality. All statistical tests were two-sided. Compared with stage I, TL was inversely associated with stage III (OR = 0.63, 95% CI = 0.52 to 0.78) and stage IV carcinomas (OR = 0.14, 95% CI = 0.08 to 0.24) overall and among individual tumor subtypes. TL was inversely related to peritoneal metastasis overall (OR = 0.39, 95% CI = 0.22 to 0.68) and among serous carcinomas (OR = 0.28, 95% CI = 0.11 to 0.68). In multivariable models unadjusted for stage, TL was associated with lower endometrial carcinoma-specific mortality (HR = 0.74, 95% CI = 0.61 to 0.91); however, adjustment for stage eliminated the survival advantage. Similar relationships with all-cause mortality were observed. TL is associated with lower stage and mortality among women with aggressive endometrial carcinomas, suggesting transtubal spread is clinically important. Future studies should evaluate whether detection of intraluminal tumor cells is prognostically relevant.
MOLLUSCUM CONTAGIOSUM OF THE SOLE.
Authors: MARY H. BUNNEY, JOHN A. A. HUNTER, MARIE M. OGILVIE
Journal: British Journal of Dermatology (1969)

SUMMARY.— A case is reported of molluscum contagiosum on the sole of the foot, which was diagnosed virologically. The difficulty of making the diagnosis on clinical grounds in this site is emphasized. The diagnosis may rather be missed than rare.
Virus Infection of Cells in Mitosis. III. Cytology of Mitotic and Amitotic HEp-2 Cells Infected With Measles Virus&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Bernard Roizman, Ann E. Schlueder-Berg
Journal: JNCI Journal of the National Cancer Institute (1962)

Journal Article Virus Infection of Cells in Mitosis. III. Cytology of Mitotic and Amitotic HEp-2 Cells Infected With Measles Virus Get access Bernard Roizman, Bernard Roizman Department of Microbiology, School of Medicine and School of Hygiene and Public Health, Johns Hopkins University, and the Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Ann E. Schlueder-Berg Ann E. Schlueder-Berg Department of Microbiology, School of Medicine and School of Hygiene and Public Health, Johns Hopkins University, and the Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 28, Issue 1, January 1962, Pages 35–53, https://doi.org/10.1093/jnci/28.1.35 Published: 01 January 1962 Article history Received: 12 June 1961 Published: 01 January 1962
Establishment of Four Mouse Hybridoma Cell Lines Producing Monoclonal Antibodies Reactive With &lt;italic&gt;ras&lt;/italic&gt; Oncogene Product p21&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: N Kuzumaki, A Oda, S Yamagiwa, N Taniguchi, H Kobayashi, T Oikawa
Journal: JNCI Journal of the National Cancer Institute (1986)

With the use of proteins derived from Escherichia coli cells expressing the v-H-ras gene product as immunogens and an enzyme-linked immunosorbent assay with whole cells for a screening method, 4 BALB/c mouse hybridoma cell lines (rp-12, rp-28, rp-35, and rp-38) were isolated that produced monoclonal antibodies (MoAbs) showing higher reactivity with murine ras gene-activated cell lines than with normal cell lines. All the MoAbs complexed p21ras from the ras gene-activated cell lines in Western immunoblot analysis and demonstrated a binding property of p21ras to guanine nucleotides. The indirect immunofluorescence assay revealed that MoAbs rp-12 and rp-28 stained the murine and human H- or K-ras-activated cell lines, and MoAbs rp-35 and rp-38 not only stained these cell lines but also weakly stained a human N-ras-activated cell line. All these MoAbs stained the murine fibroblast lines with lower intensity, but they did not stain a human fibroblast line. Further, positive reactions with MoAb rp-12 were seen against human melanomas, but there was no reaction against nevi. The rp-12, rp-28, rp-35, and rp-38 antibodies are useful additions to the MoAbs reacting with p21ras reported previously.
Who Benefits From Maintenance Therapy in Acute Promyelocytic Leukemia?
Authors: Edmond Marzbani, Elihu Estey
Journal: Journal of the National Comprehensive Cancer Network (2012)

Acute promyelocytic leukemia (APL) is remarkable for its upfront mortality rate from disseminated intravascular coagulation and its high cure rate with therapy. Although induction and consolidation regimens continue to evolve, newer approaches combine an anthracycline with or without cytarabine and the highly effective differentiating drugs all-trans retinoic acid and arsenic trioxide. Early trials showed a benefit of maintenance therapy on overall survival, although this benefit has been less clear in subsequent trials. This review assesses the differences in these trials and outlines a rational approach to maintenance therapy in APL, generally advising against maintenance in patients who underwent adequate consolidation therapy, particularly if they presented with low-risk disease (WBC < 10,000) and experienced molecular complete remission after completion of consolidation.
Prognostic Significance of K-<i>ras</i> Codon 12 Mutations in Patients With Resected Stage I and II Non–Small-Cell Lung Cancer
Authors: Stephen L. Graziano, Gary P. Gamble, Nancy B. Newman, Lynn Z. Abbott, Michelle Rooney, Sulagna Mookherjee, Melissa L. Lamb, Leslie J. Kohman, Bernard J. Poiesz
Journal: Journal of Clinical Oncology (1999)

PURPOSE: The aim of this study was to investigate the prognostic importance of codon 12 K-ras mutations in patients with early-stage non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We identified 260 patients with surgically resected stage I (n = 193) and stage II (n = 67) NSCLC with at least a 5-year follow-up. We performed polymerase chain reaction analysis of DNA obtained from paraffin-embedded NSCLC tissue, using mutation-specific probes for codon 12 K-ras. RESULTS: K-ras mutations were detected in 35 of 213 assessable specimens (16.4%). K-ras mutations were detected in 27 of 93 adenocarcinomas (29.0%), one of 61 squamous cell carcinomas (1.6%), five of 39 large-cell carcinomas (12.8%), and two of 20 adenosquamous carcinomas (10%) (P = .001). G to T transversions accounted for 71% of the mutations. There was no statistically significant difference in overall survival for all patients with K-ras mutations (median survival, 39 months) compared with patients without K-ras mutations (median survival, 53 months; P = .33). There was no statistically significant difference in overall or disease-free survival for subgroups with stage I disease, adenocarcinoma, or non–squamous cell carcinoma or for specific amino acid substitutions. The median survival time for stage II patients with K-ras mutations was 13 months, compared with 38 months for patients without K-ras mutations (P = .03). CONCLUSION: Codon 12 K-ras mutations were more common in adenocarcinomas than in squamous cell carcinomas. For the subgroup with stage II NSCLC, there was a statistically significant adverse effect on survival for the presence of K-ras mutations. However, when the entire group was considered, the presence of K-ras mutations was not of prognostic significance in this cohort of patients with resected early-stage NSCLC.
Onset of bronchodilation with fluticasone/formoterol versus fluticasone/salmeterol
Authors: Guy Brusselle, René Aalbers, Tammy McIver, Birgit Grothe, Anna Bodzenta-Lukaszyk
Journal: European Respiratory Journal (2012)

Background:  Rapid bronchodilation has been identified as a key attribute of ICS/LABA combination therapy for asthma. This post - hoc analysis assessed the onset of bronchodilation with fluticasone propionate/formoterol fumarate (FLUT/FORM) and fluticasone propionate/salmeterol xinafoate (FLUT/SAL).   Methods:  202 adults with asthma (forced expiratory volume in 1 sec [FEV 1 ] reversibility of ≥15%) were randomized to 12 weeks9 treatment with either FLUT/FORM (pMDI; 100/10 or 250/10 μg b.i.d. [treatment doses]; n=101) or FLUT/SAL (pMDI; 100/50 or 250/50 μg b.i.d. [treatment doses]; n=101) in an open-label, parallel-group study. The percentage of patients with onset of bronchodilation within 5 min and 120 min post-dose was assessed on days 0 and 84. Onset of bronchodilation was defined as the first time point post-dose with a ≥12% increase in FEV 1  versus pre-dose.   Results:  Baseline mean FEV 1  was 2.1±0.6 L (reversibility 27.6±12.8%) and 2.1±0.5 L (reversibility 24.9±9.9%) in the FLUT/FORM and FLUT/SAL groups, respectively. On day 0, a significantly greater proportion of patients had an onset of bronchodilation with FLUT/FORM than FLUT/SAL within 5 min (38.6% vs 14.0%; odds ratio [OR] 4.0; 95% CI 2.0, 8.0) and within 120 min post-dose (78.0% vs 64.0%; OR 2.0; 95% CI 1.1, 3.9). This was sustained over 12 weeks; on day 84, the percentage of patients with an onset of bronchodilation was greater with FLUT/FORM than FLUT/SAL within 5 min (16.3% vs 2.0%; OR 9.6; 95% CI 2.1, 42.9) and within 120 min post-dose (51.0% vs 35.1%; OR 1.9; 95% CI 1.1, 3.4).   Conclusion:  FLUT/FORM consistently provided more rapid bronchodilation than FLUT/SAL in patients with asthma over 12 weeks of therapy.
SoNar, a Highly Responsive NAD+/NADH Sensor, Allows High-Throughput Metabolic Screening of Anti-tumor Agents
Authors: Yuzheng Zhao, Qingxun Hu, Feixiong Cheng, Ni Su, Aoxue Wang, Yejun Zou, Hanyang Hu, Xianjun Chen, Hai-Meng Zhou, Xinzhi Huang, Kai Yang, Qian Zhu, Xue Wang, Jing Yi, Linyong Zhu, Xuhong Qian, Lixin Chen, Yun Tang, Joseph Loscalzo, Yi Yang
Journal: Cell Metabolism (2015)