tbuckley/cabot-search huggingface dataset:
Clinical impact of chemotherapy-induced thrombocytopenia in patients with gynecologic cancer.
Authors: G L Goldberg, D G Gibbon, H O Smith, C DeVictoria, C D Runowicz, E R Burns
Journal: Journal of Clinical Oncology (1994)

PURPOSE AND METHODS This retrospective analysis of 501 patients with gynecologic cancer treated with chemotherapy evaluates the relationship between platelet count and clinical bleeding, as well as the clinical effects of platelet transfusion therapy. Thrombocytopenic patients were divided into six groups according to platelet counts, and major or minor bleeding manifestations were documented. Thrombocytopenia was defined as a platelet count less than 100,000/microL. RESULTS Thrombocytopenia occurred in 182 (36.3%) patients over 808 of 1,546 chemotherapy cycles (52%). No intracranial or life-threatening bleeding occurred in any patient. The majority of patients (139 [76.4%]) had no clinical bleeding. Minor bleeding, such as purpura, occurred in 34 patients (18.7%) and 44 cycles (5.4%). Major bleeding occurred in nine patients (4.9%) and 10 cycles (1.3%). Five major bleeding events occurred in 49 patients with platelet counts between 0 and 10,000/microL. Forty-three of these patients received platelet transfusions. Thirty-eight of 43 transfused patients (88.3%) had no bleeding. Of the remaining five patients, two were transfused prophylactically with no effect. Three major bleeding events occurred in patients with platelet counts that ranged from 11,000 to 20,000/microL, but these were due to chronic instrumentation or trauma. In patients with platelet counts more than 20,000/microL, major bleeding occurred only from necrotic metastatic lesions. Random-donor platelet transfusions provided inconsistent increments in platelet counts. Overall, 27.5% of patients achieved the expected increase in platelet number based on units of platelet concentrate transfused. The use of single-donor or human leukocyte antigen (HLA)-matched platelets did not provide greater increments in those patients who were refractory to random-donor platelets. CONCLUSION Platelet counts &gt; or = 10,000/microL are not associated with spontaneous major bleeding. Prophylactic platelet transfusions in patients with gynecologic malignancies and chemotherapy-induced thrombocytopenia should be limited to those with platelet counts &lt; or = 10,000/microL, provided they are not bleeding and have no major anatomic or pathophysiologic precursors of bleeding.
Scintigraphic detection of metastatic melanoma using indium 111/DTPA conjugated anti-gp240 antibody (ZME-018).
Authors: J M Kirkwood, R D Neumann, S S Zoghbi, M S Ernstoff, E A Cornelius, C Shaw, T Ziyadeh, J A Fine, M W Unger
Journal: Journal of Clinical Oncology (1987)

We evaluated the toxicity, pharmacokinetics, and localization of a monoclonal IgG2 alpha murine anti-human melanoma (gp240) antibody (ZME-018) that recognizes a tumor-associated cell surface glycoprotein of 240,000 molecular weight present in most melanomas. The antibody was conjugated with DTPA (diethylenetriamine pentaacetic acid) and labeled by chelation of 111In. One mg of antibody labeled with 5 mCi of 111In was infused, together with 0 to 40 mg of "cold" carrier ZME-018. The blood clearance, urinary excretion, and in vivo localization were determined in 26 patients. Scintigraphic images were obtained at 24 hours and 72 hours in all patients. Mild toxicity occurred in one patient. The half-time clearance of labeled monoclonal murine antibody (MoAb) from the blood increased from 16.1 hours at an antibody dose of 1 mg to 35.9 hours at 40 mg. Males showed faster clearance from the blood than did females or a single castrated male, perhaps due to selective concentration of antibody in the testes. Nonspecific uptake in liver, spleen, bone marrow, and intestine was seen in all patients. The percentage of known metastatic foci detected increased with the total dosage of antibody, from 23% at doses less than or equal to 5 mg, to 65%, 87% and 78% for 10, 20, and 40 mg, respectively. We conclude that at doses of greater than or equal to 10 mg, ZME-018 is a safe and potentially useful agent for the scintigraphic detection of metastatic malignant melanoma.
Wrong biochemistry results
Authors: I. D Watson
Journal: BMJ (2002)

Editor—In their editorial Ismail and Barth discuss the possibility of getting wrong biochemistry results, particularly when immunoassays are done.1 Laboratories try to detect these problems and provide an accurate, clinically relevant result. But the large number of assays done has resulted in widespread reliance on automation, particularly for hormones, and the “one size fits all” approach inherent in this makes the likelihood of inaccurate results quite high.

What is needed is fit-for-purpose assays on these automated platforms. We are aware, though, of the problems that this may present: we have experienced difficulty in persuading a company that the female testosterone values that its machine produces are analytically incorrect and may lead to inappropriate clinical action if preceded by an oestradiol assay (table). The fact that we elicited similar findings from other centres through a computer mailbase and added this weight of evidence to ours did not matter to the company or, worryingly, to the Medical Devices Agency. 

Until companies recognise that, in a clinical governance setting, no-blame reporting is constructive criticism requiring positive action, then inappropriate interventions will continue to affect patients. More critical oversight of analysis and its clinical implications by the Medical Devices Agency is vital. We need confidence that any problem will be addressed either cooperatively or by effective monitoring.
Prognostic influence of comorbidities in idiopathic pulmonary fibrosis (IPF)
Authors: Svenja Ehlers-Tenenbaum, Ute Oltmanns, Karin Palmowski, Thomas Muley, Miriam Schaaf, Arne Warth, Philipp A. Schnabel, Claus P. Heussel, Felix J.F. Herth, Michael Kreuter
Journal: European Respiratory Journal (2014)

Introduction:  Comorbidities have a significant influence on the clinical course of IPF. However, their prognostic impact is not fully understood.   Methods:  Patients with IPF were selected from the database of our tertiary referral center for interstitial lung diseases and reviewed for details on patient comorbidities, their frequency per patient and overall survival data. .   Results:  Between 1/2004-12/2011, 272 IPF patients were identified: 75% male, 74% ex-/smokers (median 30 PY), medians: age 70 years, vital capacity 72% predicted, diffusion capacity 44% predicted. Comorbidities were found in 88% of patients and the number of comorbidities per patient was 1 in 19%, 2 in 19%, 3 in 21% and g3 in 29%. In a comorbidom analysis (n=107) after a median follow up of 56 months, median survival was 42 (95% CI 23-61) months. Median survival was significantly longer in patients with ≤ 3 comorbidities (n=70, 60 months) compared to patients with 4 comorbidities (n=37, 25 months, p=0,03). In a multivariate analysis, survival was significantly influenced by lung cancer (HR 5.7, pl0.0001), depression (HR 4.4, p=0.007) and cardiovascular diseases (HR 2.32, p=0.015). Coronary artery disease (univariate, p=0.047) and diabetes mellitus (HR 1.84, p=0.067) were of borderline significance.   Conclusion:  Comorbidities are frequent in IPF patients and their cumulative incidence impacts on survival, especially lung cancer and depression. Future research should focus on improved screening and treatment of comorbidities in these severely compromised patients and assess the potential impact on quality of life and survival rates.
Smoke-free zones and higher taxes reduce smoking in young people, US study finds
Authors: Susan Mayor
Journal: BMJ (2015)

Legislation banning smoking in the workplace and higher taxes on cigarettes are associated with a significant reduction in the number of adolescents starting to smoke and with a reduction in smoking in young adults, a US study has shown.

The study, published in JAMA Pediatrics , looked at the effects of smoke-free laws on a group of nearly 4000 12 to 18 year-olds taking part in the National Longitudinal Survey of Youth.1 Study participants …
Comparison of pulmonary and extra pulmonary characteristics in allogeneic hematopoietic stem cell transplantation recipients with healthy controls
Authors: Meral Bosnak Guclu, Gulsah Bargi, Zeynep Aribas, Burcu Camcioglu, Muserrefe Nur Karadalli, Zeynep Arzu Yegin, Zeynep Sahika Aki, Gülsan Turkoz Sucak
Journal: European Respiratory Journal (2014)

Background: Limited number of studies reported reduction in exercise capacity, muscle strength and abnormalities in lung functions in allogeneic hematopoetik stem cell transplantation (allo-HSCT) recipients. However, pulmonary and extrapulmonary characteristics in allo-HSCT recipients have not been compared with healthy controls so far.

Aim: To compare submaximal exercise capacity, pulmonary functions, respiratory and peripheral muscle strength, dyspnea and fatigue perception and depression in allo-HSCT recipients with healthy controls.

Methods: Forty patients (41.55±12.03 years) previously underwent allo-HSCT (>100 days status post transplantation) and 30 controls (45.77±10.02 years) were compared. Functional exercise capacity using 6-minute walk test (6MWT), respiratory muscle strength (MIP, MEP) using a mouth pressure device, peripheral muscles strength using dynamometer, dyspnea using Modified Medical Research Council (MMRC) dyspnea scale, fatigue using Fatigue Impact Scale (FIS), depression using Beck Depression Scale (BDS), pulmonary functions were evaluated

Results: Six-MWT distance, MIP, MEP, quadriceps femoris and hand grip muscle strength were significantly lower, Modified MMRC, BDS and FIS scores were significantly higher in recipients compared with controls p<0.05).

Conclusion: Functional exercise capacity, respiratory and lower extremity muscle strength are reduced, fatigue, dyspnea perception and depression are worsened in allo-HSCT recipients. Randomized prospective studies are needed to investigate the effects of respiratory and peripheral muscle training and aerobic exercise training in allo-HSCT recipients.
Cyclin‐Dependent Kinase 9 Inhibition Protects Cartilage From the Catabolic Effects of Proinflammatory Cytokines
Authors: Jasper H. N. Yik, Zi'ang Hu, Ratna Kumari, Blaine A. Christiansen, Dominik R. Haudenschild
Journal: Arthritis & Rheumatology (2014)

Cyclin-dependent kinase 9 (CDK-9) controls the activation of primary inflammatory response genes. The purpose of this study was to determine whether CDK-9 inhibition protects cartilage from the catabolic effects of proinflammatory cytokines.Human chondrocytes were challenged with different proinflammatory stimuli (interleukin-1β [IL-1β], lipopolysaccharides, and tumor necrosis factor α) in the presence or absence of either the CDK-9 inhibitor flavopiridol or small interfering RNA (siRNA). The expression of messenger RNA (mRNA) for inflammatory mediator genes, catabolic genes, and anabolic genes were determined by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. Cartilage explants were incubated for 6 days with IL-1β in the presence or absence of flavopiridol. Cartilage matrix degradation was assessed by the release of glycosaminoglycan (GAG) and cleaved type II collagen (COL2A) peptides.CDK-9 inhibition by flavopiridol or knockdown by siRNA effectively suppressed the induction of mRNA for inducible nitric oxide synthase by all 3 proinflammatory stimuli. Results from NF-κB-targeted PCR array analysis showed that flavopiridol suppressed IL-1β induction of a broad range of inflammatory mediator genes (59 of 67 tested). CDK-9 inhibition also suppressed the induction of catabolic genes (matrix metalloproteinase 1 [MMP-1], MMP-3, MMP-9, MMP-13, ADAMTS-4, and ADAMTS-5), but did not affect the basal expression of anabolic genes (COL2A, aggrecan, and cartilage oligomeric matrix protein) and housekeeping genes. Flavopiridol had no apparent short-term cytotoxicity, as assessed by G6PDH activity. Finally, in IL-1β-treated cartilage explants, flavopiridol reduced the release of the matrix degradation product GAG and cleaved COL2A peptides, but did not affect long-term chondrocyte viability.CDK-9 activity is required for the primary inflammatory response in chondrocytes. Flavopiridol suppresses the induction of inflammatory mediator genes and catabolic genes to protect cartilage from the deleterious effects of proinflammatory cytokines, without affecting cell viability and functions.
Expression of Heme Oxygenase Isoenzymes 1 and 2 in Normal and Asthmatic Airways
Authors: SAM LIM, DAVID GRONEBERG, AXEL FISCHER, TIMOTHY OATES, GAETANO CARAMORI, WALDO MATTOS, IAN ADCOCK, PETER J. BARNES, KIAN FAN CHUNG
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Heme oxygenase (HO) is considered to be an antioxidant enzyme that catabolizes heme to produce carbon monoxide (CO) and biliverdin. We determined the expression and distribution of HO-1 and HO-2, two isoenzymes of HO, in the airways of patients with asthma, and determined the effect of inhaled corticosteroid therapy. Immunostaining for both enzymes was widely distributed in the airways' submucosa, particularly in airway epithelium and submucosal macrophages (CD68(+)) as determined by double immunostaining. There was no difference in intensity and extent of staining in biopsies from normal subjects (n = 10) and subjects with asthma (n = 10). Following 1 mo of treatment with inhaled corticosteroids (budesonide 1,600 microg/d), there was no significant change in the expression and distribution of either HO-1 or HO-2 in the airways' submucosa in eight subjects with mild asthma, despite a significant reduction in airway eosinophils and a reduction in bronchial responsiveness to methacholine. Levels of exhaled nitric oxide were significantly reduced, but exhaled CO levels remained unchanged by the treatment. Treatment with a placebo inhaler (n = 8) had no effects on these parameters. Thus, both HO-1 and HO-2 are extensively distributed equally in normal subjects and subjects with asthma, and are not modulated by inhaled corticosteroid therapy in subjects with asthma. HO may be an important endogenous antioxidant enzyme.
Dynamics of the etiological structure from sputum of patients with pneumonia
Authors: Nelya Bisenova, Aigerim Yergalieva
Journal: European Respiratory Journal (2013)

Microbiological characteristics of respiratory infections change specific structure. Therefore, constant microbiological monitoring of specific structure, specific properties, and antibiotic resistance is required.  The purpose of this research is to produce a dynamic analysis of microbial spectrum from sputum of patients with pneumonia at the National Medical Research Centre.  From 2007 to 2012, 400 strains of microbes were isolated from sputum of patients with pneumonia. Identification was determined by the microbiological computer analyzer «Vitek 2-Compact».  Comparative analysis of the microbial landscape showed that S.pneumoniae had a high level of detection. It increased from 37.5% in 2007 to 45% in 2012. In the same period, sputum detection of Enterococcus faecalis increased from 1.7% to 10%, and of Candida albicans from 1.7% to 4.2%. At the same time, there was a decrease in detection of Streptococcus pyogenes by 3 times and Moraxella catarrhalis by 2.5 times.  Thus, our results showed that the basic pathogen of pneumonia was Streptococcus pneumoniae.
Phase I trial of cyclosporine-induced autologous graft-versus-host disease in patients with multiple myeloma undergoing high-dose chemotherapy with autologous stem-cell rescue.
Authors: S Giralt, D Weber, M Colome, M Dimopoulos, R Mehra, K Van Besien, J Gajewski, B Andersson, I Khouri, D Przepiorka, B von Wolff, K Delasalle, M Korbling, D Seong, R Alexanian, R Champlin
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine the feasibility and toxicity of inducing autologous graft-versus-host disease (GVHD) with cyclosporine in patients with multiple myeloma undergoing autologous stem-cell transplantation. PATIENTS AND METHODS Fourteen multiple myeloma patients with a median age of 50 years (range, 41 to 63) were enrolled. The median time from diagnosis to transplant was 651 days (range, 229 to 3,353). Ten patients had primary refractory disease, two were in first remission, and two were responsive to salvage therapy. The preparative regimen consisted of thiotepa, busulfan, and cyclophosphamide. Cyclosporine was administered daily for 28 days after the stem-cell infusion, and the dose was adjusted to maintain whole-blood cyclosporine levels between 50 and 150 ng/dL in the first seven patients (low-level group) and between 150 and 300 ng/dL in the other seven patients (high-level group). RESULTS All patients achieved neutrophil engraftment a median of 11 days after transplant. Four patients developed &gt; or = grade 2 hepatic toxicity, six developed &gt; or = grade 2 nephrotoxicity, and four developed reversible cardiac toxicity. Only one treatment-related death occurred. Cyclosporine was withheld in seven patients for a median of 6 days because of renal and/or liver dysfunction. One patient developed clinical skin GVHD, which responded to corticosteroid therapy. Six patients developed histologic evidence of GVHD without clinical signs of GVHD (subclinical GVHD). The incidence of clinical and subclinical GVHD was similar in both cyclosporine groups. Three of 11 patients assessable for response achieved remissions. Three patients experienced disease progression 80, 160, and 354 days after transplant. Ten patients are alive without progression between 56 and 444 days after transplant. CONCLUSION Induction of autologous GVHD by posttransplant cyclosporine is feasible and well tolerated in patients with multiple myeloma.
Neoadjuvant treatment for operable breast cancer in the community: Applications of cooperative group trials
Authors: R. A. Somer, R. Dougherty, M. Koch, E. Rodler, K. Sharan, G. Grana
Journal: Journal of Clinical Oncology (2008)

11529 Background: Neoadjuvant treatment for operable breast cancer is increasing based on clinical guidelines that are typically derived from randomized phase 3 cooperative group trials whose results establish a standard of care. However, the majority of cancer therapy is given in the community. There is controversy about the applicability of these studies to community practice. The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-27 (JCO (24)2019–27, 2006) found the preoperative addition of four cycles of docetaxel to four cycles of AC significantly improved response rates in women with operable breast cancer. We studied whether community practice can achieve similar results in women with operable breast cancer treated in a neoadjuvant approach. Methods: Retrospective analysis of a cancer registry database from a community center consisting of 36 women with operable breast cancer who were treated preoperatively with four cycles of doxorubicin and cyclophosphamide followed by docetaxel was performed. Clinical and pathologic response to therapy was evaluated and compared to the peer-reviewed, published standard. Results: Of 36 patients reviewed, a total of 21 patients were identified for analysis. The average age of the patient was 54. The average tumor size was 6.4 cm, with 48% having estrogen receptor (ER) positive disease. The complete clinical response (CCR) was found to be 42.9% v 63.6%, p = 0.066; the partial clinical response (PCR) 38.1% v 27.1%, p = 0.320; the overall clinical response (CCR + PCR) 81.0 v 90.7; and the complete pathologic response (CPR) 23.8% v 26.1%, p = 1.00, compared to results published in NSABP B27, respectively. The data was tested against the standard as established by the NSABP B-27 by using the Fisher exact test. There were no significant differences between the two groups in regards to response rates. Sample size was too small to compare disease-free and overall survival. Conclusions: Although our sample contained a large proportion of ER positive tumors, women with operable breast cancer treated with four cycles of doxorubicin and cyclophosphamide followed by four cycles of docetaxel in the community setting achieve similar outcomes compared to national standards. Current breast cancer trials reflect community practice. No significant financial relationships to disclose.
Assessing the learning curve for EUS(b)-FNA in comparison with classical 'blind' TBNA
Authors: Ilya Sivokozov, Olga Lovacheva, Irina Shumskaya
Journal: European Respiratory Journal (2012)

Background. Transbronchial needle aspiration (TBNA) is a challenge due to very flat learning curve. Now, EUS and EBUS significantly improved the results of TBNA. Nevertheless, number of 9learning9 procedures to become an expert in this type of biopsy is controversial.  Aim. To evaluate the learning curve for EUS(b)-FNA versus classical 9blind9 TBNA in a tertiary center.  Materials. Patients with chest lymphadenopathy with main suspicion for sarcoidosis referred to the bronchoscopy were randomized 1:1 to EUS(b)-FNA (arm A) or classical blinded TBNA (Arm B). All procedures performed under local anesthesia by experienced endoscopist with no skills for both techniques, under expert control. Position 7 or 4L were punctured in both groups. Age, sex, size of lymph nodes by CT, number of biopsies, duration of procedure, complications, quality of diagnostic material and diagnostic yield were assessed.  Results. 56 patients were enrolled into the study, with 28 for each arm. Patients were comparable in age (mean 44,2 yrs) and sex (men 34/56), and size of target lymph nodes (27±5 mm). There were no complications. Median duration of procedure in arm A reduced from 9 min for first 5 pts to 4 min in last 5 pts (p 80%) reached plateau after 15 patients (42 biopsies) in group A and 25 pts (67 punctures) in group B (p  Conclusion. The learning curve of EUS(b)-FNA estimates a number of procedures to achieve an acceptable level of performance in 15 procedures, whereas classical TBNA needs 10 procedures more.
Factors influencing to HRQOL of patients with mild to moderate persistent asthma in Japan; sub-analysis of GAIA study
Authors: Kumiya Sugiyama, Takeshi Fukuda, Mitsuru Adachi, Ken Ohta, Yuji Tohda, Shunsuke Shoji, Terumasa Miyamoto
Journal: European Respiratory Journal (2013)

Background : Health Related Quality of Life (HRQOL) is one of the most important measures to evaluate health condition of patients. However, a few studies have examined the relationship between characteristics of asthma patient and HRQOL.

Objective : Purpose of this study is to evaluate the factors influencing on HRQOL in patients with asthma.

Methods : A total of 280 patients with mild to moderate persistent asthma registered for GAIA Study (Trial ID:UMI03250) were used for analysis at basement, as the data sets for MOS 8-Item Short-Form Health Survey (SF-8).

Results : SF-8 scores at basement were as same value as compared with Japanese national norms. VT (Vitality) and MH (Mental Health) for female, PF (Physical Functioning) and PCS (Physical Component Summary) for older patients (≥65) were significantly lower than those of male (p=0.022, p=0.025), those of younger patients (<65) (p=0.018, p=0.025). PF and VT for patient’s duration of asthma over 10 years were significantly lower than those duration of asthma under 10 years (p=0.024, p=0.022). In patients with sputum, PF, SF (Social Functioning), VT, and PCS were significantly lower than those without sputum (p=0.006, p=0.004, p=0.050, p=0.020). No significant differences were found between patients with and without asthma control medications such as ICS/LABA combination therapy, patients of %FEV1<80% and %FEV1≥80%, atopic and non-atopic type.

Conclusion : Factors influencing to SF-8 were sex difference, age, duration of asthma, and sputum. The treatment of asthma should be discussed under improvement of HRQOL.