tbuckley/cabot-search huggingface dataset:
Clinical applications of hematopoietic growth factors.
Authors: J M Vose, J O Armitage
Journal: Journal of Clinical Oncology (1995)

PURPOSE AND DESIGN To review the current clinical uses, ongoing investigations, and future applications of hematopoietic growth factors. Approved cytokines, as well as cytokines not yet released for general use, are included in this review. RESULTS Clinical applications of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin, the three recombinant hematopoietic growth factors currently commercially available for clinical use in the United States, are discussed. Macrophage colony-stimulating factor (M-CSF), interleukin-3 (IL-3), PIXY321, stem-cell factor (SCF), IL-1, IL-6, and IL-11 represent cytokines not yet approved; the majority of these newer agents have their principal action at an earlier time point in the hematopoietic cascade than the currently approved cytokines. Current clinical uses of hematopoietic growth factors include decreasing cytopenias associated with chemotherapy, those due to congenital or acquired bone marrow failure states, those that occur after high-dose chemotherapy and bone marrow transplantation, peripheral-blood progenitor mobilization, and supportive care of leukemia patients. CONCLUSION Hematopoietic growth factors have made a significant impact on the prevention of infections associated with chemotherapy-induced neutropenia, shortening of neutropenia following high-dose chemotherapy and progenitor-cell transplantation, and chemotherapy-associated anemia. Cost-effectiveness and cost-benefit analyses in future phase III and pharmacologic studies will aid in the assessment of these agents.
US drug agency approves drug for low sexual desire in women
Authors: Michael McCarthy
Journal: BMJ (2015)

The US Food and Drug Administration (FDA) has approved the first drug for the treatment of women with low sexual desire. The drug, flibanserin, which is made by Sprout Pharmaceuticals, of Raleigh, North Carolina, will be marketed under the name Addyi.

“Today’s approval provides women distressed by their low sexual desire with an approved treatment option,” said Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research in a statement announcing the drug’s approval.

The approval comes after the agency was subject to an intense lobbying campaign by …
Gender differences in the pulmonary acute inflammatory response to concentrated ambient particles in mice
Authors: Kelly Yoshizaki, Jose Mara Brito, Thaís Moraes do Nascimento Santos, Paulo Hilário Nascimento Saldiva, Luiz Fernando Ferraz da Silva, Thaís Mauad, Mariangela Macchione
Journal: European Respiratory Journal (2012)

The reason why the female gender has a significantly higher risk factor to respiratory illnesses compared to males is not known, although some researchers speculate that sex hormones may interfere in the proneness to these diseases. The physiologic hormonal fluctuation during the menstrual cycle is known to induce changes in nasal epithelium and lung inflammation. The aim of this study is to analyze how the hormonal cycling of female mice is affected by near-ambient levels of pollution. Particulate matter (PM) was concentrated by an ambient particle concentrator (APC). 14 Male (M) Balb/C mice were divided into two groups: without exposure to PM (M/A;control group) and exposed to PM. 28 Female Balb/C were divided into four groups, according to the estrous cycle. Only female mice from proestrus (PE) and estrus (E) were enrolled. Those from PE were divided into two subgroups: with and without exposure to PM (PE/PM and PE/A). Mice from E were also divided into two subgroups: with and without exposure to PM (E/PM and E/A). Neutral and acidic nasal mucus content was quantified in epithelium through morphometry. Inflammatory cells were analyzed by bronchoalveolar lavage (BAL). APC exposure in M/PM increased both neutrophils in BAL (p=0.031) and neutral mucus content (p=0.016) from nasal epithelium, when compared to PE/PM. No statistical difference was observed to E/PM. In the M/A group, it was observed an increase in both total BAL (p=0.042) and macrophages (p=0.043) when compared to PE/A. These findings indicate that near-ambient levels of PM exposure promoted a higher neutrophil recruitment in male than in female mice in proestrus.
Problems in diagnosis and treatment of Staphylococcus haemolyticus endocarditis in a hemodialysis patient
Authors: Henk Louagie, Marc Struelens, Raf De Ryck, Geert Claeys, Gerda Verschraegen, Dirk Vogelaers, Norbert Lameire, Mario Vaneechoutte
Journal: Clinical Microbiology and Infection (1998)
PSA density as a predictor of aggressive prostate cancer on repeat prostate biopsy
Authors: S. Rogosin, L. Collins, S. Mongoue-Tchokote, B. H. Blank, T. M. Beer, M. Mori, M. Garzotto
Journal: Journal of Clinical Oncology (2007)

5007 Background: Prostate biopsy procedures carry a high false-negative rate. However, since Gleason score is strongly associated with cancer-specific mortality; efforts to identify men who harbor high-grade prostate cancer will likely assist in patient selection for repeat biopsies. We sought to identify risk factors for the detection of aggressive prostate cancer (Gleason ≥ 7) on repeat biopsy. Methods: Clinical and pathologic variables collected from subjects undergoing a repeat biopsy included all prostate specific antigen (PSA) values, PSA density (PSAD), PSA doubling time (PSADT). PSADT was examined using PSAs up to the first biopsy, and also in an exploratory analysis using both pre- and post-biopsy PSAs. Predictors of aggressive prostate cancer were identified using recursive partitioning and a stepwise Cox regression model. Results: 511 patients with initial negative biopsies underwent 1,319 biopsy procedures. Median follow-up was 3.7 years. Aggressive cancer was diagnosed in 52 of 511 (10.18%) patients. Recursive partitioning analysis selected PSAD as the sole factor for distinguishing high- and low-risk groups. Based on K-M analysis, a PSAD &lt;= 0.304 ng/ml/cc carried 2 and 5 year aggressive cancer detection rates of 4% (± 1.9%) and 9% (± 3.5%) respectively, whereas a PSAD &gt; 0.304 ng/ml/cc carried cancer detection rates of 23% (± 11.9%) and 36% (±15.3%) at 2 and 5 years (p-value &lt;.0001). Independent prognostic factors included (HR, 95% CI): PSA &gt;= 9.7 (2.565, 1.404 - 4.688), PSAD 0.13 - &lt; 0.19 ng/ml/cc (0.423, 0.179 - 0.999) and volume &gt;= 43.3 cc (0.454, 0.247 - 0.833). PSADT became significant when all PSA data were analyzed: PSADT &lt; 2 years (4.203, 1.894 - 9.325) and PSADT &gt;= 5 years (0.17, 0.89- 0.326). Conclusions: In decision tree analysis, a high PSAD is predictive of aggressive prostate cancer on a repeat biopsy. In addition, high PSA, lower PSAD and prostate volume are predictive of aggressive prostate cancer. However in follow-up using all PSA values, a PSADT &lt; 2 yrs. becomes the most significant predictor of aggressive cancer. Such data may help identify the most appropriate patients for a repeat biopsy and could reduce the rate of unnecessary biopsies and the inherent over-treatment of prostate cancer. No significant financial relationships to disclose.
NFkB location in T-cells is promising to monitor immunosuppression after lung transplantation
Authors: Urte Sommerwerck, Monika Lindemann, Bjoern E. Kleibrink, Thomas Rabis, Gerhard Weinreich, Markus Kamler, Helmut Teschler, Peter A. Horn, Vera Rebmann
Journal: European Respiratory Journal (2014)

Background : In solid organ transplantation, immunosuppression (IS) by calcineurin inhibitors (CI) or mTOR inhibitors (mTORI) is assessed by blood levels, which do not reflect the biological activity towards effector cells (EC). The transcription factor nuclear factor kappa beta (NFkB) mediates cell survival, proliferation and growth arrest by regulation of cytokine and chemokine expression. Therefore, nuclear NFkB location (nNFkB-l) might mirror the activity of EC.   Aims and objectives:  We investigated if the nNFkB-l in T-cells represents a suitable parameter to monitor the biological activity of IS.   Methods: n NFkB-l was analysed in unstimulated and TNF-a stimulated T-cells in 13 lung transplant recipients and 7 healthy controls by Multispectral Imaging Flow Cytometry. The results were linked to IS and clinical data. In parallel the number of IFN-g releasing peripheral blood cells (PBLs) after CD3/CD28 stimulation was defined by ELISpot.   Results:  An increased proportion of unstimulated or TNF-a stimulated CD8+ T-cells with nNFkB-l (mean±SEM %) was found in unstable patients e.g. with infections (35.1±7.4 or 45.9±7.2; N=5) compared to stable patients (19.0±3.2, p=0.02 or 30.4±2.7, p=0.06; N=8) or controls (19.3±4.2, p=0.03 or 31.9±3.61, p=0.1, N=7). A trend for higher nNFkB-l in CD8 cells was found in patients with mTORI (33.2±9.0; N=5) compared to CI treated patients (20.2±2.5, p=0.2; N=8). Regarding function, the number of IFN-g producing PBLs correlated with nNFkB-l in CD8 stimulated T-cells (r=0.69, p=0.002; N=17).   Conclusion:  These results provide first evidence that the nNFkB-l in T-cells might be a promising and functionally relevant tool to monitor IS after lung transplantation.
Does infection with Chlamydia pneumoniae and/or Helicobacter pylori increase the expression of endothelial cell adhesion molecules in humans?
Authors: A. Schumacher, I. Seljeflot, A.B. Lerker⊘d, L. Sommervoll, J.E. Otterstad, H. Arnesen
Journal: Clinical Microbiology and Infection (2002)
Alprazolam as a neuroleptic adjunct in the emergency treatment of schizophrenia [published erratum appears in Am J Psychiatry 1992 Aug;149(8):1129]
Authors: J G Barbee, D M Mancuso, C R Freed, A A Todorov
Journal: American Journal of Psychiatry (1992)

While neuroleptics remain the mainstay of drug intervention in the emergency management of psychosis, a variety of agents have received study as alternatives or adjuncts to these drugs in an attempt to improve the safety and efficacy of acute treatment. The purposes of this study were to investigate the efficacy and safety of alprazolam as a neuroleptic adjunct for schizophrenic patients in psychotic relapse and to clarify the effects of combination treatment on specific aspects of the psychotic process.Twenty-eight acutely psychotic patients with schizophrenia who were admitted to an emergency psychiatric service were randomly assigned to treatment with either haloperidol and alprazolam or haloperidol with placebo under double-blind conditions. Drug administration lasted 72 hours.Both groups improved significantly. The combination-treated group required significantly less medication and had 56% fewer dystonic reactions. The addition of alprazolam was most effective for symptoms of excitement and uncooperativeness, particularly in the initial hours of treatment.The combination of alprazolam and haloperidol seems to be the most effective for agitated patients, particularly in the first 48 hours of treatment. It may also result in fewer dystonic reactions.
Adjuvant chemotherapy in operable breast cancer: cyclophosphamide, methotrexate, and fluorouracil versus chlorambucil, methotrexate, and fluorouracil--11-year results of Swiss Group for Clinical Cancer Research trial SAKK 27/82.
Authors: H J Senn, R Maibach, M Castiglione, W F Jungi, F Cavalli, S Leyvraz, J P Obrecht, O Schildknecht, P Siegenthaler
Journal: Journal of Clinical Oncology (1997)

To compare two adjuvant combination chemotherapies, cyclophosphamide, methotrexate, and fluorouracil (CMF) and chlorambucil, methotrexate, and fluorouracil (LMF), for patients who had undergone potentially curative surgery for unilateral breast cancer, in terms of relapse, survival, and toxicity.Selection criteria was as follows: stage pT1-3a, N+ or N-, M0, less than 72 years of age. Eligible patients were randomized to receive either CMF (cyclophosphamide 100 mg/m2 orally on days 1 to 14, methotrexate 40 mg/m2 intravenously (I.V.) on days 1 and 8, fluorouracil 600 mg/m2 I.V. on days 1 and 8) or LMF (Leukeran [Wellcome A.G., Bern, Switzerland] 5 mg/m2 orally on days 1 to 14 with the some I.V. cytostatic drugs). Follow-up examinations were performed every 3 months during the first 3 years after mastectomy, and every 6 months thereafter.A total of 246 patients were randomized, of whom 232 who were fully eligible and contribute to the analyses presented here. No statistically significant difference in favor of adjuvant CMF over LMF emerges after a median follow-up duration of 11.2 years, for either overall survival (P = .15) or disease-free survival (P = .14). A consistent trend suggestive of a possible relative benefit associated with CMF should be pointed out. However, CMF presents a significantly worse toxicity profile as concerns hematologic parameters as well as alopecia, nausea, and vomiting.This prospective trial has not identified a statistically significant difference in disease-free survival or overall survival between the two adjuvant regimens LMF and CMF. Although a trend in favor of CMF has been observed in premenopausal patients, this has to be weighted against its definitely more pronounced toxicity profile.
COPD GOLD stage 1: Is it really a disease?
Authors: Jean Bourbeau, Wan Tan, Robert Cowie, Paul Hernandez, Ken Chapman, Andrea Benedetti, Palmina Mancino, Maria Fernanda Sedeno, Pei Zhi Li, Sean Ling, Lu Zheng, Sarah Bernard
Journal: European Respiratory Journal (2011)

Background: GOLD sought to standardize COPD definition and severity. The clinical meaning of GOLD 1 and it putative progressive nature remains uncertain.

Objective: To determine the characteristics of COPD GOLD stage 1 and it progressive nature.

Methods: This research is part of the Canadian Cohort Obstructive Lung Disease (CanCOLD), a prospective longitudinal study with a population-based sample of COPD. Subjects are recruited from 9 cities in one of 4 subsets (sex and age matched): 1) COPD GOLD ≥2; 2) GOLD 1; 3 and 4) non-COPD controls, i.e., at risk (ever smoker) and healthy. Measurements were done at baseline and 3-5 years later.

Results: This preliminary analysis included 111 subjects. GOLD 1 subjects as compared to GOLD ≥2 had less wheezing (20% vs 41%, p=0.048), physician-reported asthma (14% vs 41%, p=0.007), and better health status (SF-36): PCS (49 vs 46, p=0.191) and MCS (54 vs 50, p=0.002). GOLD 1 subjects were less likely to have a physician-diagnosed COPD (6% vs 17%, p=0.031) and to be prescribed respiratory drug (16% vs 38%, p=0.007). Subjects with GOLD 1 as compared to non-COPD control reported more dyspnea MRC ≥2/5 (39% vs 20%, p=0.082) but chronic bronchitis and level of health status (SF-36) were similar. Annual change in FEV1 were -62 ml/year (p<0.001) for GOLD 1, -32 ml/year (p=0.006) for GOLD ≥2 and -25 ml/year (p=0.18) for non-COPD. Annual change in physical health (SF-36 PCS) were -0.42 (p=0.086) for GOLD 1, -0.89 (p=0.023) for GOLD ≥2 and -0.20 (p=0.54) for non-COPD.

Conclusions: Early disease or GOLD stage 1 appears to be associated with more rapid decline in FEV1 and worsened health status.

Funding: CIHR RxD and the Respiratory Health Network of the FRSQ.
Surgical Management of Gunshot Injuries of the Large Intestine
Authors: T G Parks
Journal: Journal of the Royal Society of Medicine (1979)

Eighty-eight patients suffering from gunshot injuries of the large intestine were admitted during an 8-year period to the Royal Victoria Hospital, Belfast. In 16 patients who died there was an average of 3.8 intra-abdominal organs injured. No patient with an isolated colonic or rectal injury succumbed.
Airway symptoms and lung function among male workers in the aftermath of an oil tank explosion
Authors: Jens-Tore Granslo, Bjørg Eli Hollund, Ågot Irgens, Magne Bråtveit, Cecilie Svanes, Bente Elisabeth Moen
Journal: European Respiratory Journal (2011)

Background:  In 2007 storage tanks with a heterogeneous mixture of hydrocarbons, sulphur compounds and hydrochloric acid exploded and caught fire in a Norwegian industrial harbour. Pollution in air and soil produced an intense smell until clean up was terminated in 2009. Respiratory symptoms and lung function was assessed 1.5 years after the explosion among male fire-fighters, clean- up workers, and employees working in the industrial harbour at the time of the accident.   Methods:  163 exposed men (fire-fighters, clean- up workers, and local employee at the time of the accident) (response rate 86%) and 90 male controls (home address > 20 km from the accident place), aged 18-67 years participated with a questionnaire and spirometry (response rate 59%). Regression analyses of the relationship between outcomes and exposure were performed, adjusting for smoking, occupational exposure (job exposure matrix), Phadiatop® status, infection last month, and age (symptoms).   Results:  Exposed men reported more daily cough; odds ratio 2.0 [95% confidence interval 1.1, 3.7]; dyspnoe walking up hill 2.6 [95% CI 1.3, 5.2]) and sore throat 2.3 [95% CI 1.1, 4.7]. FEV 1 % predicted was 89.0 among exposed and 91.1 among controls, adjusted difference -1.9 [95% CI -6.6, 2.8].   Conclusion:  Fire-fighters, clean up workers and local employee exposed to air pollution from an oil tank explosion had more airway symptoms than a control group 1.5 years after the accident, but not significantly different lung function.
Pragmatic controlled trial of azithromycin for asthma in adults
Authors: David Hahn, Michael Grasmick, Scott Hetzel
Journal: European Respiratory Journal (2011)

Background: Macrolides are a novel treatment for asthma.

Aims: To investigate macrolide effects after treatment.

Methods: Randomized (RAND), placebo-controlled, double-blind parallel group, practice-based trial of azithromycin (AZ), 600 mgm for 3 days, then weekly for 11 weeks or placebo (PLA) with follow up 1 year from randomization. Eligible subjects who declined randomization received open-label (OL) azithromycin.

Results: Compared to RAND, OL subjects had more adult-onset asthma, chronic sinusitis, severe persistent asthma and hospitalizations for asthma. Compared to PLA, OL subjects had significant improvements in asthma symptoms and quality of life (QOL) at 1 year (9 months post-treatment). AZ subjects did not have comparable benefits (Table).

View this table:

Outcomes at 1 year compared to pretreatment





The proportions of subjects achieving a QOL score change ≥1 unit at 9 months (6 months after finishing treatment) were 22% for PLA, 27% for AZ and 80% for OL (P<.001 compared to PLA). At 1 year the comparable figures were 21%, 36% and 54% (P=.072).

Conclusions: OL subjects had severe asthma and persisting benefits, number needed to treat (NNT) = 2 to 4. AZ subjects had milder asthma and did not show benefits, although this study was not powered to detect the NNT = 7 suggested by some results. Azithromycin should be considered as adjunctive therapy for severe asthma unresponsive to guideline treatments. Larger studies are warranted to confirm results in severe asthma and to explore potential benefits in milder asthma.
Montreal cognitive assessment in COPD
Authors: Alexandru F. Crisan, Cristian Lazar, Emanuela Tudorache, Cristian Oancea, Ovidiu Fira-Mladinescu, Alexandru Crisan, Voicu Tudorache
Journal: European Respiratory Journal (2014)

Background/Purpose.  Chronic obstructive pulmonary disease (COPD), especially in severe forms, is commonly associated with multiple cognitive problems. Montreal Cognitive Assessment test (MoCA) is used to detect cognitive impairment evaluating several areas: visuospatial, memory, attention and fluency. We followed the impact of acute and stable COPD phases on cognition status using MoCA questionnaire.   Methods.  38 patients (pts.) smokers, COPD group D (28 stable and 10 acute exacerbation AECOPD) and 10 healthy subjects (control group, CG) having the same level of education and anthropometric data performed spirometry, MoCA questionnaire; blood gases and inflammatory markers were collected.   Results.  In the MoCA test (total score) AECOPD patients showed a significant lower score (means cognitive alteration) than patients in stable phase and in the control group (15±2,64 AECOPD vs. 20,07±2,39 COPD vs. 26,2±1,03 CG, pl0,0001). Major differences were recorded at attention (0,15 AECOPD vs. 0,375 COPD vs. 0,9 CG, p=0,0003) and visuospatial/executive (15 ±2,64 AECOPD vs. 20,07 ±2,39 COPD vs. 27,2 ±1,03 CG, p=0,0002). Beside the boundry blood gases, we found a moderate correlation between MoCA and inflammatory markers (r=-0.492 p= 0.034 for fibrinogen, respectively r=-0.461, p= 0.048 for CRP).   Conclusions.  According to this questionnaire, COPD significantly decreases the cognitive status in advanced and acute stages of the disease. Although hypoxemia is recognized as a factor that alters the cognition, the present study advances the idea that in addition to hypoxemia the inflammatory factors might play an important role.
Relation between preferred and optimal cadences during two hours of cycling in triathletes
Authors: S Argentin, C Hausswirth, T Bernard, F Bieuzen, J-M Leveque, A Couturier, R Lepers
Journal: British Journal of Sports Medicine (2006)

To determine whether the integrated electromyographic signal of two lower limb muscles indicates preferred cadence during a two hour cycling task.Eight male triathletes performed right isometric maximum voluntary contraction (MVC) knee extension and plantar flexion before (P1) and after (P2) a two hour laboratory cycle at 65% of maximal aerobic power. Freely chosen cadence (FCC) was also determined, also at 65% of maximal aerobic power, from five randomised three minute sessions at 50, 65, 80, 95, and 110 rpm. The integrated electromyographic signal of the vastus lateralis and gastrocnemius lateralis muscles was recorded during MVC and the cycle task.The FCC decreased significantly (p<0.01) from P1 (87.4 rpm) to P2 (68.6 rpm), towards the energetically optimal cadence. The latter did not vary significantly during the cycle task. MVC of the vastus lateralis and gastrocnemius lateralis decreased significantly (p<0.01) between P1 and P2 (by 13.5% and 9.6% respectively). The results indicate that muscle activation at constant power was not minimised at specific cadences. Only the gastrocnemius lateralis muscle was affected by a two hour cycling task (especially at 95 and 110 rpm), whereas vastus lateralis remained stable.The decrease in FCC observed at the end of the cycle task may be due to changes in the muscle fibre recruitment pattern with increasing exercise duration and cadence.