tbuckley/cabot-search huggingface dataset:
Granulopoiesis in “Preleukemic” Mice With Anemia Induced by Rauscher Leukemia Virus, Variant a2
Authors: Hal E. Broxmeyer, Leonard Koltun, Joseph LoBue, Torgny N. Fredrickson, Albert S. Gordon
Journal: JNCI Journal of the National Cancer Institute (1975)

To understand further the hematopoietic dyscrasias induced by a variant (a) of Rauscher leukemia virus (RLV), we used Escherichia coli endotoxin to stress the hematopoietic system of control and RLV/a-infected BALB/c mice. During the preleukemic stages of virus infection, there was slight splenomegaly without peripheral blood erythroblastosis. Granulocyte release and tissue mobilization mechanisms appeared unaffected by the RLV/a infection. Both RLV/a-infected and control mice reacted to endotoxin with peripheral granulocytosis and peritoneal granulocyte mobilization, though the circulating granulocyte levels in RLV/a-treated mice initially were lower than those in controls. Spleens of RLV/a-infected animals were larger than those of controls, but both responded to endotoxin with elevated numbers of granulocytes and erythroblasts. Since numbers of bone marrow erythroblasts in both groups of mice were decreased after endotoxin, stem cell competition and/or shunting of stem cells from marrow to spleen may have been involved. Endotoxin also induced rapid falls in hematocrit levels in both groups. These studies suggested that RLV/a-infected mice can be a model to study 1) erythropoietic dysfunction uncomplicated by defective granulopoietic release and tissue mobilization control mechanisms, and 2) progression of evolving granulocytic leukemia.
A randomized trial of CHOP chemotherapy with or without melatonin in patients with favorable prognosis large B-cell lymphoma
Authors: A. Sarma, M. A. Rodriguez, F. Cabanillas, N. H. Dang, P. McLaughlin, F. B. Hagemeister, B. Pro, J. Romaguera, A. Younes, E. A. Grimm
Journal: Journal of Clinical Oncology (2004)

8066 Background: Melatonin is a hormone made in the pineal gland that regulates sleep and influences other hormonal body functions. Studies by Lissoni, et al. (Supportive Care in Cancer. 5: 126,1997) also suggest a myeloprotective effect when administered with chemotherapy. To assess the myeloprotective effect of melatonin on patients receiving CHOP chemotherapy, we conducted the following trial. Methods: Eligible patients had newly diagnosed, histologically proven, large B-cell lymphoma with a favorable prognosis (M.D. Anderson Tumor Score<3. Rodriguez, et al. Ann Oncol. 3: 711–717, 1992). Patients were treated with CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) every three weeks and were randomized to take or not to take melatonin 20 mg daily by mouth for 18 weeks starting on day 1 of course1. Weekly CBC's with differentials were obtained after cycle 1. The primary endpoint was the incidence of neutropenia (neutrophil count ≤ 500) after the first course of chemotherapy. Results: Between 1998 and 2001, 112 evaluable patients were enrolled on the study. 56 were randomized to each arm. Baseline characteristics were statistically similar between the groups. The median age was 54 and the International Prognostic Index score was ≤3 in 96% of patients. 51 patients experienced a neutrophil nadir ≤ 500 after course 1 of chemotherapy; 26 were in the arm with melatonin, 25 were in the arm without melatonin (p=0.78). Tests of association between the treatment group and secondary measured parameters including the nadir ANC, change in hemoglobin, change in platelet count, CR rate, and infection rate were not statistically significant. Overall survival was estimated to be 95% at three years in both arms. The three year failure-free survival was 75% in both treatment groups. Conclusions: The addition of melatonin to CHOP chemotherapy did not decrease the incidence of neutropenia after cycle 1 in this patient population. In addition, this study suggests that there is no improvement in neutrophil nadir, CR rate, infection rate, or change in hemoglobin or platelet counts with the addition of melatonin. No significant financial relationships to disclose.
CA 19-9 and CA 125 Levels in the Sera of Normal Blood Donors in Relation to Smoking History&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: P J Green, S K Ballas, P Westkaemper, H G Schwartz, T L Klug, V R Zurawski
Journal: JNCI Journal of the National Cancer Institute (1986)

CA 19-9 and CA 125 serum levels were evaluated among smoking and nonsmoking healthy blood donors. Smoking did not elevate mean levels of either CA 19-9 or CA 125 in the sera of 496 of these blood donors from Philadelphia, PA. Mean CA 19-9 levels were slightly higher among females than among males. Among smokers there was a trend toward slightly increasing CA 19-9 serum levels with increased age, which was significant among the male donors. Trends toward slightly decreased mean serum levels of CA 125 among smokers were of borderline significance. Serum CA 19-9 and CA 125 levels in none of these donor subpopulations was elevated compared to levels reported by others for gastrointestinal or ovarian carcinoma patients, respectively. Therefore, smoking status should not interfere with use of either the CA 19-9 or CA 125 assays for diagnostic or monitoring applications.
Broad spectrum of virulence of pseudomonas aeruginosa clones characterized in a murine airway infection model
Authors: Antje Munder, Florian Wölbeling, Sarah Dethlefsen, Yang Zang, Huiming Peng, Erich Gulbins, Burkhard Tümmler
Journal: European Respiratory Journal (2013)

The ubiquitous bacterium  Pseudomonas aeruginosa  ( P. aeruginosa ) occurs not only in various environmental habitats but also plays a severe and important role as a human pathogen. Especially infections in the lungs of patients with cystic fibrosis (CF), Chronic Obstructive Pulmonary Disease (COPD) or immunocompromised people deteriorate the course of the diseases and are often life threatening. Here, we tested strains that are representative for the twenty worldwide most common  P. aeruginosa  clones. All strains were examined in a standardized acute murine airway infection model at a dose of 1.5 x 10 6  CFU. We monitored survival, lung function, body weight and temperature and scored the infection course of the mice. As end point parameters lung bacterial numbers, lung histopathology and inflammatory cytokine response were taken. The spectrum of global virulence within the strain collection was extremely broad, so the environmental clone B420 isolated from a German river showed almost no pathogenic potential towards mice, whereas a clone EC21 (Pacific Ocean) turned out to be highly pathogenic and 100% lethal. A similar observation was made assessing the clinical isolates; there were early CF isolates which affected mice only marginally (clone C40A) or showed attenuated virulence like strain PA14, but we also observed highly virulent strains, such as clone OC2E (CF isolate), clone E429 (ventilation associated pneumonia isolate) and clone F469 (COPD isolate). The F469 COPD strain had the highest pathogenic potential. In conclusion it can be stated that high virulence in  P. aeruginosa  is not limited to strains found as clinical isolates but also occurs in environmental strains.
How severe pulmonary hemorrhage influence on surgical tactics at patients with lung abscess and gangrene
Authors: Evgeny Korymasov, Armen Benyan, Sergey Pushkin, Alexander Reshetov, Yurii Syzrantsev, Ildar Kameev, Anton Tepikin, Mikhail Medvedchikov-Ardiya
Journal: European Respiratory Journal (2012)

OBJECTIVE. Surgical management at patients with acute lung abscesses and lung gangrene based on lung destruction sizes, presence of complications, degree of SIRS, efficacy of therapeutic methods, particularly severe pulmonary hemorrhage (blood loss more than 500 ml).  METHODS. We have carried out an analysis of our experience of treatment of patients with lung abscesses and gangrene. There were 1842 patients with lung abscess and 176 patients with lung gangrene from 1985 till 2011 years. We have observed severe pulmonary hemorrhage at 45 patients (2,4%) with lung abscess and at 23 patients (13,1%) with lung gangrene.  RESULTS. At 1797 patients with lung abscess without severe pulmonary hemorrhage therapeutic methods of treatment were effective at 1490 patients (83,0%), chronicity of disease – at 274 patients (15,2)%. We have performed 3 pneumonectomies, 121 lobectomies, 102 wedge resections. Mortality – 33 patients (1,8%). At 153 patients with lung gangrene without severe pulmonary hemorrhage regress of inflammation was achieved in 117 cases (76,5%). We performed 8 pneumonectomies, 69 lobectomies, 16 wedge resections. Mortality – 6 patients (3,9%).  From 68 patients with severe pulmonary hemorrhage 10 dead before operation. To another 58 patients at first we perform roentgenoendovascular embolization of bronchial arteries, then 16 pneumonectomies, 42 lobectomies. General mortality – 26 patients (38,2%).  CONCLUSIONS. At patients with acute lung abscesses and lung gangrene operation must be performed at period of pneumofibrosis or at appearance of severe pulmonary hemorrhage.
A phase II study of sunitinib administered in a continuous daily regimen in patients with cytokine-refractory metastatic renal cell carcinoma (mRCC)
Authors: P. H. De Mulder, J. Roigas, S. Gillessen, S. Srinivas, P. Pisa, N. Vogelzang, G. Fountzilas, C. Peschel, C. Baum, B. Escudier
Journal: Journal of Clinical Oncology (2006)

4529 Background: Renal cell carcinomas are known for their vascularity and production of high levels of VEGF. Sunitinib malate (SU11248), an oral, multitargeted tyrosine kinase inhibitor of multiple receptors including VEGFR, PDGFR, KIT, RET, and FLT3, has previously demonstrated significant efficacy in 168 patients (pts) with mRCC, with a 42% objective response rate (ORR) at 50 mg/day in 6-week (wk) cycles of 4 wks on treatment followed by 2 wks off. This study sought to determine the efficacy and safety of single-agent sunitinib in mRCC when administered in a continuous 37.5 mg/day regimen. Methods: Pts with histologically proven mRCC, refractory to a cytokine-based regimen, were enrolled in this open-label, multicenter, phase II study. Eligibility criteria included measurable disease, ECOG PS 0/1, and adequate organ function. Pts were randomized to receive sunitinib in the morning (AM) or in the evening (PM) at a dose of 37.5 mg/day, with individual doses subsequently titrated based on tolerability. The primary endpoint was RECIST-defined ORR. Secondary endpoints includedprogression-free survival, adverse events (AEs) and quality of life measures. Results: A total of 88/100 planned pts have been randomized to date: AM (43) and PM (45), and enrollment will be completed by end January 2006. 44 pts have been on continuous sunitinib treatment at 37.5 mg/day for &gt;16 wks (3), &gt;12 wks (9), &gt;8 wks (12), and &gt;4 wks (20). 2 pts (2.3%) discontinued (colon perforation and renal insufficiency) and 9 (10.2%) dose reduced to 25 mg/day due to grade 2/3 AEs: mucositis (2), hand-foot syndrome (2), thrombocytopenia (2), asthenia (1), nausea/diarrhea (1), and neutropenia (1). Preliminary efficacy data show some tumor shrinkage in the majority of patients evaluated at 4 wks, with 3 initial partial responses. There has been no significant difference between pts who received AM or PM doses. The most commonly reported AEs were mucositis, fatigue, hair/skin discoloration, and hand-foot syndrome. Conclusions: Sunitinib administered at a continuous dose of 37.5 mg/day was generally well tolerated; only a few patients required treatment breaks and/or dose reduction. Preliminary efficacy data are encouraging. Mature data will be presented. [Table: see text]
Does technology matter? One intensive care unit's experience
Authors: Russell Graham, Roberta Melton, Adam Mullaly, Stanley Rhone, James Fink
Journal: European Respiratory Journal (2012)

Background : Pneumatic nebulizers (PN) can add significant flow to the circuit and can harbor harmful pathogens.1 Use of a PN with mechanical ventilation (MV) often results in incomplete nebulization with retrograde contamination from the patient. Vibrating mesh nebulizers (VMN) have a physical barrier between the aerosol pathway and the medication reservoir, reducing risk of contamination. We hypothesized VMN would provide more effective therapy and potentially reduce the risk of VAP. Method : The Neuroscience ICU Respiratory Therapists initiated a QI project, trialing a VMN (Aerogen, Galway, Ireland), locating one controller in each room to avoid cross-contamination issues as part of a VAP reduction strategy. All medicated aerosol was perormed by VMN. Cumulative data was compiled for the 12 months prior. The new method (VMN) was used for 9 months, resuming the old method for an additional 60 day period (to act as an additional control) Results : 

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Table 1





Use of VMN resulted in a 15% drop in vent days, with a 19% increase during the 60 day return. LOS decreased by 28.7% during the study period. There was no statistically significant change in VAP rate, possibly due to the change in weighted value from the decreased vent days. Conclusions : VMN was preferred by the therapists. In this instance, the advent of technology was felt to make a significant impact on patient care. Further study of the impact of choice of aerosol delivery device on patient outcome is indicated.

1 Respir Care 2005;50(6):725-741.
Pentostatin in the treatment of advanced hairy cell leukemia.
Authors: E H Kraut, B A Bouroncle, M R Grever
Journal: Journal of Clinical Oncology (1989)

2'-Deoxycoformycin (pentostatin [dCF]), a potent inhibitor of adenosine deaminase (ADA), was administered in a biweekly low-dose (2 to 4 mg/m2) intravenous (IV) schedule to patients with advanced hairy cell leukemia. Twenty-three patients were treated, including 12 patients previously treated by splenectomy and five patients treated with interferon. Twenty-one of 23 patients had objective responses, including 20 who achieved a complete remission (CR). Responses occurred rapidly, with an average time to CR of 5.4 months. Treatment was not continued once CR was achieved, and 15 of 20 patients remain in remission with an average duration of 12.6 months. CRs were achieved in both patients previously treated with interferon (three of five) and patients with marked splenomegaly (three of three). Relapses, when seen, have occurred in the bone marrow alone and the one patient who required retreatment was reinduced into CR. Toxicity has been mild and reversible, with nausea and vomiting, conjunctivitis, and skin rash as the main complications of treatment. dCF is the most effective single agent in the treatment of hairy cell leukemia, inducing a high percentage of CRs in all subgroups. Two multiinstitutional trials are now underway to compare its effectiveness v alpha interferon.
An overview analysis of the time people spend outdoors
Authors: B L Diffey
Journal: British Journal of Dermatology (2010)

An important factor in determining our exposure to sunlight, and the consequent impact on skin health and vitamin D status, is the time we spend outdoors.To determine estimates of the typical times per day spent outdoors during weekdays, weekends and holidays during a summer season.A number of published studies giving data on the time per day spent outdoors by people were reviewed and a meta-analysis performed. From these data summary estimates of the average time per day outdoors were extracted.Time spent per day outdoors during weekdays and weekends is positively skewed, with a normal distribution of times outdoors during holidays. The median times per day outdoors during weekdays and weekends gave pooled estimates of 1·04 and 1·64 h, respectively. Corresponding values for the pooled estimates of mean times outdoors during these two periods were 1·43 and 2·38 h. The mean time per day outdoors during holiday exposure is 5-6 h.Summer-long distribution of times spent outdoors on a daily basis exhibits a highly skewed nature that highlights the difference between our adventitious and recreational exposure. Over the course of a summer season, when people are outside, they spend on average of 1-2 h per day outdoors.
Sublinguial allergen extract immunotherapy in a rush pattern to reach the maintainance faster
Authors: Naren Pandey, Saurabh Kole, Surendra Prasad Singh, Swati Gupta Bhattacharya, Suman Kumar, S. Bibhore
Journal: European Respiratory Journal (2011)

Introduction:  Slit (sub lingual immunotherapy Rush immunotherapy was tried on some patients to evolve some faster and affordable immunotherapy modality to make the patient achieve the maintenance pleatu within a very short time. Conventional method of immunotherapy is administered with long durations; rush immunotherapy is super fast methodology in attaining the maintenance/boosting module, which requires hospitalization and other precautionary methods, and multiple allergen vaccines to be administered within short span of time. But in this method, it was found that within 15-20 days the relief of the immunotherapy was reached.   Material & method:  186 patients out of which 48 with urticaria allergy and 138 with allergic Rhinitis & Bronchial Asthma were selected. The therapy consists of administration of four vials of allergen extracts, 1st vial: 1:25,00, 2nd vial 1:2,50, 3rd vial 1:25, and 4th vial 1:10 dil. The 1st & the 2nd concs were administered in daily 6 hourly schedules in a graphically rising manner. The patients had been given pre-medication. Blood examination and IgG & IgE level estimation were done before & after 8 weeks.   Results:  Some of the patients showed local skin reactions which subsided without drugs and no systemic reaction was noted. There was substantial decrease in IgE & increased IgG level, significant & marked satisfactory relief was observed in the patients symptomatology, thus the procedure was graded as a very fast & affordable & SAFE immunotherapy.
Association of Cyclin D1 (CCND1) gene A870G polymorphism and clinical outcome of EGFR-positive metastatic colorectal cancer patients treated with epidermal growth factor receptor (EGFR) inhibitor cetuximab (C225)
Authors: W. Zhang, J. Yun, O. A. Press, M. Gordon, D. Y. Yang, N. Mallik, A. Sherrod, S. Iqbal, H. J. Lenz
Journal: Journal of Clinical Oncology (2004)

3518 Background Cetuximab (C225) is a chimeric anti-EGFR monoclonal antibody with efficacy against EGFR-positive metastatic colorectal cancer. Recently, the link between EGFR signaling and the cell cycle has been identified. In vitro studies show blockade of EGFR by C225 can induce cell cycle arrest in the G1 phase which mediated by inhibition of interactions between cyclins and CDKs and increases expression of the cell cycle inhibitor p27KIP1. A frequent A870G polymorphism in the final codon of exon 4 of the Cyclin D1, leads gene alternatively spliced to produce two different mRNA transcripts [a] and [b] was also identified. In vivo studies have indicated this polymorphism can affect the prognosis of patients with different types of solid tumors. We hypothesized that CCND1 A870G polymorphism will predict clinical outcome in EGFR-positive metastatic colorectal cancer patients treated with EGFR inhibitor Cetuximab(C225). Methods Cyclin D1 A870G gene polymorphism was tested using PCR-RFLP method in genomic DNA extracted from peripheral blood from 39 metastatic colorectal cancer patients enrolled in a phase II EGFR inhibitor Cetuximab(C225) clinical trial. ResultsWe found a significant association between A870G polymorphism and overall survival of patients treated with Cetuximab(C225). With median follow-up 8.7 months (range 2.5, 11.7) and median survival time 4.8 months (95%C.I 2.7, 8.5), Patients with AA homozygous genotype survived a median time of 2.3 months (95%C.I 2.1, 5.7) compared with those have homozygous GG genotype 4.4 months (95%C.I 1.8, 9.8+) or heterozygous AG genotype 8.5 months(95%C.I 5.5, 11.7+), respectively (p<0.05, logrank test). ConclusionsThese data suggest that Cyclin D1 A870G polymorphism may be a potential prognostic molecular marker for clinical outcome of the EGFR-positive metastatic colorectal caner patients treated with third line EGFR inhibitor Cetuximab (C225). Prospective studies are needed to confirm these preliminary findings. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Chiron NCI; NIH; Roche; Lilly; Pharmacia; Bayer; Bristol-Myers Squibb; Chiron; Aventis; Genentech; ImClone; Cellpathway; Newbiotics; Sanofi
Usage of Information Sources by General Practitioners<sup>1</sup>
Authors: B Strickland-Hodge, M H Jeqson
Journal: Journal of the Royal Society of Medicine (1980)

Questionnaires were sent to approximately 500 general practioners in five areas of one National Health Service Region; there was a 52% response. Certain characteristics of each general practitioner, which were collected from the questionnaire and medical lists, were used to assess how information was used by different ‘types’ of general practitioner. Generally, sources of information emanating from the pharmaceutical industry are used more to introduce the new product, while the ‘professional’ sources such as medical journals are used more to evaluate it. Younger doctors used Drug and Therapeutics Bulletin more than did their colleagues, and single-practice doctors found the representative to be more useful than did joint-practice doctors.
Chronic kidney disease as effect modifier in the association between the use of tiotropium respimat and mortality
Authors: Katia Verhamme, Nico van Blijderveen, Silvana Romio, Bruno Stricker, Guy Brusselle, Miriam Sturkenboom
Journal: European Respiratory Journal (2013)

Background: Tiotropium, a long acting anticholinergic, is delivered via Handihaler or via Respimat. RCTs suggest that use of Tiotropium Respimat increases the risk of dying. One of the mechanisms is higher plasma concentrations of Tiotropium Respimat, especially in patients with chronic kidney disease (CKD).  Objective: To investigate whether renal function is an effect modifier in the association between Tiotropium Respimat and mortality.  Methods: Within the IPCI database, we defined a cohort of patients, ≥ 40 years, being prescribed either Tiotropium Respimat or Handihaler in 2008-2011. From these prescriptions, episodes of use were defined and patients were followed until end of treatment episode, end of study or mortality; whichever came first. For each treatment episode, kidney function (eGFR and/or proteinuria) in the 1 year prior to episode start was assessed. Risk of mortality was estimated with adjusted Cox proportional regression analysis. To study effect modification, patients were stratified between normal kidney function or stage 3-5 CKD.  Results: 11,287 patients provided 24,522 episodes of Tiotropium use. 496 patients died during exposure (Handihaler or Respimat). Use of Respimat 5 μg was associated with almost 30% increased risk of dying compared to Handihaler (HR adj  1.28, 95% CI 1.02-1.62). In patients with CKD 3-5, the risk was 1.69 (95% CI 1.10-2.59). In patients with normal kidney function, the association between use of Respimat and mortality was lower and not longer significant but confidence intervals did overlap. (HR adj  1.21, 95% CI 0.48-3.05)  Conclusion: Association between the use of Respimat and mortality is higher in patients with CKD stage 3-5.