tbuckley/cabot-search huggingface dataset:
Hemodynamic effects of pneumonia
Authors: Raj Kumar, Wayne A. Wallace, Alberto Ramirez, Herbert Benson, Walter H. Abelmann
Journal: Journal of Clinical Investigation (1970)

Previous work has demonstrated that approximately one-third of patients with pneumonia have a hypodynamic circulatory response. This response is characterized by an abnormally wide arteriovenous oxygen difference, a low cardiac output, increased peripheral resistance, and an increased hematocrit. This state was found to abate in convalescence. In an attempt to elucidate the pathogenesis of this hypodynamic state, nine additional patients were studied hemodynamically during the acute phase of pneumonia before and during acute expansion of blood volume by low molecular weight dextran (seven patients) or normal saline (two patients). Five patients were restudied before and during acute blood volume expansion in convalescence. Three patients with pneumonia had a normal arteriovenous oxygen difference (< 5.5 vol%), and six patients were hypodynamic in that their arteriovenous oxygen differences were greater than 5.5 vol%. With expansion of blood volume in the acute phase of pneumonia, all patients showed an increase in cardiac output, a decrease in arteriovenous oxygen difference, and a decrease in peripheral vascular resistance; however, the percentage change in the hypodynamic patients was not as great as occurred in the patients with normal hemodynamics nor as great as occurred when restudied in convalescence. Likewise, all patients had a normal or near normal hemodynamic profile in convalescence. In addition, ventricular function in the acute phase of pneumonia was depressed. The findings suggest that the hypodynamic state associated with acute pneumonia is due to depressed myocardial contractility to which relative hypovolemia may contribute.
Mutually exclusive Th2 and Th17 bronchial gene expression signatures are associated with eosinophilia in asthma
Authors: David Choy, Aarti Shikotra, Salman Siddiqui, Deepti Nagarkar, Alexander Abbas, Chandra Ohri, Emma Doran, Claire Butler, Beverley Hargadon, Maria Shelley, Lawren Wu, Liam Heaney, Joe Arron, Peter Bradding
Journal: European Respiratory Journal (2014)

*JA and PB are co-senior authors

Background: Th2 and Th17 cytokine-dependent inflammatory pathways are potential therapeutic targets in severe asthma. The extent of the activity of these two pathways in individual patients is unclear.

Objective: To develop gene expression signatures of Th2 and Th17 cytokine activity in asthmatic airways and assess their relationships to airway pathophysiology, clinical disease expression, and biomarkers of cytokine activity.

Methods: Th2 and Th17 cytokine gene expression metrics were developed in vitro in primary human bronchial epithelial cells and used to interrogate the activity of these pathways in endobronchial tissue from patients with clinically well-characterised asthma across a spectrum of severity (n=51).

Results: We identified three clusters of cytokine gene expression in asthmatic airways: Th2-high, Th17-high and Th2/17-low. Th2-high and Th17-high patterns were mutually exclusive in individual patients, and were inversely correlated. However Th2 and Th17 signatures were both associated with airway eosinophilia. The Th17 signature was only detected in patients taking inhaled corticosteroids (ICS) while Th2-high and Th2/17-low patterns were present in ICS users and non-users. Only the Th2/17-low signature was associated with non-eosinophilic pathology.

Conclusion: Patients with severe asthma may have either a Th2-high, Th17-high or Th2/17-low pattern of airway gene expression. Low levels of blood and sputum eosinophilia predict a Th2/17-low molecular phenotype, but all three molecular phenotypes may be associated with eosinophilic disease, which may have implications for therapeutic strategies targeting inflammatory cytokines.
Osteoporosis, sarcopenia and pulmonary hypertension in relation to GOLD classification vs BODE index in COPD
Authors: Shekhar Kadam, Dipti Gothi, Jyotsna Joshi
Journal: European Respiratory Journal (2013)

Background: The prevalence of osteoporosis and sarcopenia important extra-pulmonary effects of chronic obstructive pulmonary disease (COPD) are unknown in Indain population. BODE index a prognostic index for COPD has not been studied in relation to pulmonary hypertension (PH).  Aim: To study osteoporosis, sarcopenia with duel energy xray absorptiometry (DEXA) and their relation with forced expiratory volume in one second (FEV1%). To correlate FEV1 and BODE index with pulmonary hypertension (PH).  Materials and Methods: In 30 stable COPD, bone mineral density (BMD) and fat free mass index were calculated with DEXA scan. Two groups of FEV1 (FEV1 ≥50% and FEV1  Results: All patients had low BMD (33% -osteopenia & 66% -osteoporosis) and 83.3% had sarcopenia. Chi-square test to assess the significance of osteoporosis and sarcopenia in realtion to FEV1 groups and the BODE groups was statistically insignificant (p value=0.88).  5/7 had normal PH and 2 had mild PH in group I (FEV1 ≥50%), whereas in group II (FEV1   Conclusion: Osteoporosis and sarcopenia are very common in COPD in Indian population but there is no correlation with FEV1. GOLD staging (stage III and IV) is more likely to correlate with severity of PH than BODE index.
Comparison pulmonary rehabilitation efficiency in COPD patients between with and without pulmonary hypertension
Authors: Ipek Candemir, Pinar Ergun, Dicle Kaymaz, Nilgun Mendil, Nese Demir, Nurcan Egesel, Fatma Sengul
Journal: European Respiratory Journal (2014)

The aim of study was to evaluate the efficiency of pr in COPD patients with and without PH.According to Echocardiographic diagnosis 2009 ERS/ESC guideline, patients were divided into grup1(PH unlikely) and group2(PH possible,likely). 88 stable COPD Patients underwent an 8week hospital based outpatient PR.  Dyspnea was assessed with MRC scale,health related quality of life with St.GeoergeRespiratoryQuestionnaire(SGRQ).Exercise capacity was measured using Incremental Shuttle Walk Test (ISWT) and Endurance Shuttle Walk Test (ESWT); the body composition with bioelectrical impedance method.In all patients body composition (BMI p:0,01),quality of life (SGRQ symptom,activity,total p:0,00),dyspnea sensation,exercise capasity (ISWT,ESWT,VO2 peak p:0,00) were improved. When the improvements were compared between groups, there was no statistically significant difference except change in ESWT.In grup2 increase in ESWT was more than grup1(p:0,002).  Pulmonary rehabilitation is safe and effective in COPD patients with PH. COPD patients with PH should be refered for comprehensive, multidisplinary, individually, tailored PR programs.
Regional chemotherapy devices: effect of experience and anatomy on complications.
Authors: K A Campbell, R C Burns, J V Sitzmann, P A Lipsett, L B Grochow, J E Niederhuber
Journal: Journal of Clinical Oncology (1993)

Regional hepatic arterial infusion (HAI) devices have been used for 17 years, but reports of unacceptably high complication rates have led to controversy about their use. Inadequate or misdirected infusion has been reported to occur in up to 45% of patients. We evaluated whether surgeon experience or presence of variant arterial anatomy related to risk of coagulation.We reviewed 70 patients undergoing placement of HAI catheters. Surgeons were classed as experienced after 10 procedures and arterial anatomy was evaluated angiographically with confirmation at operation. Complications were categorized as technical (17%) or chemotherapy-related (16%).Inexperienced surgeons had a technical complication rate of 37% (80% of the patients involved had standard anatomy), while experienced surgeons had a technical complication rate of 7% (P < .01). Experienced surgeons had no complications in patients with standard anatomy, while inexperienced surgeons had a 42% (eight of 19) complication rate in similar patients (P < .01).We conclude that technical complications are closely associated with surgeon experience and arterial anatomy.
An Anti-α-Fetoprotein Antibody-Daunorubicin Conjugate With a Novel Poly-&lt;sc&gt;l&lt;/sc&gt;-glutamic Acid Derivative as Intermediate Drug Carrier
Authors: Y Tsukada, Y Kato, N Umemoto, Y Takeda, T Hara, H Hirai
Journal: JNCI Journal of the National Cancer Institute (1984)

In studies on antitumor antibody-cytotoxic drug conjugates as potential antitumor agents with improved tumor specificity, daunorubicin [(DM) daunomycin] was conjugated with an affinity-purified horse antibody to rat α-fetoprotein (AFP) with a novel derivative of poly-l-glutamic acid (PLGA) as the intermediate drug carrier. A single masked thiol group first was introduced by PLGA, and the thiol group was generated from it after the linking of DM to PLGA at the carboxyl groups of PLGA. The thiol group was used selectively for binding PLGA-DM to antibody that had been modified so as to have the maleimide groups. The conjugates (DM:PLGA:immunoglobulin molar ratio, 19.6:2.8:1 or 11.8:1.1:1) were more potent than DM in in vitro cytotoxicity against the AFP-producing rat ascites hepatoma cell line AH66. In therapeutic experiments, the conjugates were more efficacious in prolonging the lives of AH66 hepatoma-bearing DONRYU rats than DM, antibody, a mixture of DM and antibody, or a conjugate similarly prepared with normal horse immunoglobulin.
Recombinant interleukin-2 by continuous infusion and adoptive transfer of recombinant interleukin-2-activated cells in patients with advanced cancer.
Authors: P A Paciucci, J F Holland, O Glidewell, R Odchimar
Journal: Journal of Clinical Oncology (1989)

Twenty-five patients with disseminated cancer (nine with renal cell carcinoma, five with melanoma, three with Hodgkin's lymphoma and chronic myelocytic leukemia [CML], two with soft tissue sarcoma, one each with large-cell lymphoma, breast cancer, and colon cancer), 13 males and 12 females, aged 25 to 68, were treated with recombinant human interleukin-2 (rIL2) by continuous infusion and adoptive transfer of autologous lymphocytes activated in vitro with IL2. Patients underwent leukapheresis on days 1, 8, 15, and 22 of the treatment. Cells, bulk activated for 20 hours in serum-free culture medium with 1,000 U IL2/mL in transfusion transfer packs as culture vessels, were transfused the following day. The infusion of IL2 by continuous infusion for six days started immediately after each adoptive transfer for 4 weekly courses. The dose of IL2 was escalated weekly in each patient; starting doses of IL2 were also escalated in subsequent cohorts of patients until maximally tolerated doses were reached. Nine patients had objective tumor regressions (three with renal cell cancer, two with Hodgkin's lymphoma, and one each with melanoma, sarcoma, breast, and colon cancer). Six responses were partial, two were minor, and one was mixed. Responding patients were maintained with IL2 by continuous infusion for six days every 6 to 8 weeks, without adoptive cell transfer. The median duration of responses was 16 weeks (3 to 60 + weeks). Tumor regression was related to the dose of IL2 (greater than or equal to 3.4 x 10(6) U/m2/d for six days) and to the in vivo lymphoproliferative effects of the lymphokine, but not to the total number of cells adoptively transferred. Side effects of treatment were transient and quickly reversible. Renal, hepatic dysfunction, and dyspnea were directly related to the dose of IL2 and to lymphocytosis. Other toxicities were mild hypotension with mild fluid retention, oral mucositis, anemia, thrombocytopenia, fever, and fatigue.
Facilitation of optimal asthma management to radically influence health policy in primary care in Ireland
Authors: Jean Holohan, Louis Coyne, Francis Guiney, Pat Manning, Basil Elnazir, Eamonn Shanahan, Terry O'Connor, Muireann Ni Chroinin, Netta Williams, Rhonda Forsythe, Pamela Logan
Journal: European Respiratory Journal (2011)

Prior to the initiation of this program guideline based care was not prioritised by health policy. Asthma control is sub-optimal in Ireland; recent primary care data shows 14% of asthma patients attended A&E, 8% hospitalised in the previous 12 months.  The Asthma Society of Ireland (ASI) developed a framework for the Dept. of Health and Health Service Executive (HSE) in collaboration with Healthcare Professional (HCP) bodies based on nationally modified guidelines (GINA) and a core program to assess the feasibility of implementing a National Asthma Program.  The ASI funded and developed an asthma management program in primary care to identify barriers and facilitators to implementation of guideline based care. 25 primary care teams completed a guideline based educational program and practical training session. Each team was given a tool-kit with spirometer, peak flow meters and diaries, patient education materials, placebo inhalers and spacers. Adherence to guidelines was facilitated with a specifically developed Electronic Patient Record. 778 patients were included in the program for 6 months.  A guideline based asthma program can be implemented successfully if practices are provided with necessary resources for diagnosis, management and patient education. HCP agreed guidelines improved patient care (92.7%), facilitated cost effective care (70.7%). Arising from this study HSE has prioritised the development of a National Asthma Program with asthma specific key performance indicators in its service plans.  Active collaboration between patient organisations, HCP and health service providers has lead to a fundamental change in asthma health policy in primary care.
Novel approach to gene expression profiling in Sézary syndrome
Authors: R.G. Pomerantz, E.D. Mirvish, G. Erdos, L.D. Falo, L.J. Geskin
Journal: British Journal of Dermatology (2010)

Background Microarray hybridization studies in Sézary syndrome (SS) have compared T lymphocytes from patients with cutaneous T-cell lymphoma with those of normal controls; a major limitation of this design is that significant inherent genetic variability of lymphocyte populations between individuals may produce differences in gene expression unrelated to disease state. Objective The objective of this study was to minimize the heterogeneity of information derived from whole-genome expression analysis and to identify specific genetic differences between highly purified malignant and nonmalignant (control) T cells from the same patient with SS. Methods Peripheral blood mononuclear cells were obtained from a patient with SS, stained with anti-T-cell receptor Vβ (TCR-Vβ) antibodies, and sorted by multiparameter flow cytometry. Malignant cells expressed the dominant TCR-Vβ; control T cells lacked the dominant TCR-Vβ but were otherwise phenotypically identical (CD3+CD4+CD45RO+). These cell populations were compared using the Illumina Inc. Sentrix Human-6 expression BeadChip system. Results Transcriptome analysis using the J5 test, which was selected for data analysis based on an efficiency analysis of competing statistical methods, showed differential expression of 44 genes between the malignant and nonmalignant cell subsets. Promyelocytic leukaemia zinc finger protein (ZBTB16) was the most profoundly upregulated gene in the malignant cell population, while interferon regulatory factor 3 (IRF3) and interferon-induced protein 35 (IFI35), which are important elements of the cellular response to viral infection, were significantly downregulated. Conclusions The results of this study suggest the feasibility of this novel comparative approach to genomic profiling in SS. Using this method, we identified several differentially expressed genes and pathways not previously described in SS. While these findings require validation in larger studies, they may be important in SS pathogenesis.
Abstract 19808: Short Term Outcomes After Use of Bone Marrow Transplantation for Management of Heart Failure: A Meta-analysis
Authors: Rohit S Loomba, Navdeep Gupta, Saurabh Aggarwal, Imtiaz Ismail, Anushree Agarwal, Atul R Chugh, Rohit R Arora, Roberto Bolli
Journal: Circulation (2014)

The role of bone marrow cell transplant in ischemic heart failure is being increasingly recognized. Multiple studies have been published evaluating their use with varying results. We aimed to perform a meta-analysis of the published literature. We searched Pubmed, EBSCO and Cochrane databases for terms “bone marrow transplant”, “stem cell transplant”, “heart failure”, “cardiac failure” and their combinations. Only studies comparing bone marrow cell transplantation via intracoronary route to placebo, and those with 6 month follow up data were included. Studies in language other than English were excluded. Results: Ejection fraction was significantly increased with the use of bone marrow cell transplant compared to placebo (mean difference 6.16% 95%CI 4.16 to 8.16, p &lt; 0.00001). No significant differences were observed in left ventricular (LV) end-systolic volume (mean difference -1.58 ml 95%CI -4.98 to 1.82, p = 0.36), LV end-diastolic volume (mean difference -0.77 ml 95%CI -3.75 to 2.22, p = 0.61) and mortality (odds ratio 1.08 95%CI 0.26 to 4.56, p = 0.92). Results of heterogeneity analysis showed significant heterogeneity only for ejection fraction endpoint (p = 0.01). Conclusion: As compared to placebo, intracoronary bone marrow cell transplant is associated with improved LV ejection fraction by 6% in ischemic heart failure patients at 6 month follow up.
Phase I trial and pharmacologic trial of sequences of paclitaxel and topotecan in previously treated ovarian epithelial malignancies: a Gynecologic Oncology Group study.
Authors: S O'Reilly, G F Fleming, S D Barker, J R Walczak, M A Bookman, W P McGuire, R J Schilder, R D Alvarez, D K Armstrong, I R Horowitz, R F Ozols, E K Rowinsky
Journal: Journal of Clinical Oncology (1997)

PURPOSE A phase I and pharmacologic study to evaluate the feasibility of administering paclitaxel (PTX) in combination with topotecan (TPT) without and with granulocyte colony-stimulating factor (G-CSF) in women with recurrent or refractory ovarian cancer. PATIENTS AND METHODS TPT was administered as a 30-minute infusion daily for 5 days and PTX was given as a 24-hour infusion (PTX-24) either before TPT on day 1 or after TPT on day 5. Each patient received both schedules on an alternating basis every 3 weeks. Sequential dose escalation of TPT or PTX-24 without and with G-CSF resulted in five dosage permutations of TPT/PTX (mg/ m2): 0.75/135 without G-CSF and 0.75/135, 1.25/135, 1.50/135, and 1.25/170 with G-CSF. RESULTS Twenty-two patients received 109 courses of therapy. Dose-limiting myelosuppression consistently occurred at the first TPT/PTX-24 dose level (0.75/135 mg/m2) in the absence of G-CSF support. Although the addition of G-CSF resulted in reduced rates of complicated neutropenia, the incidences of dose-limiting neutropenia and thrombocytopenia were unacceptably high after the doses of either TPT or PTX-24 were increased. Paired analysis showed similar hematologic toxicities between the two sequences of drug administration. The pharmacologic behavior of both TPT and PTX-24 was not altered by drug sequencing. Major antitumor responses occurred in 40% of patients with measurable and assessable disease, including 45% and 9% of patients with potentially cisplatin-sensitive and -resistant tumors, respectively. CONCLUSION The recommended doses of TPT on a daily times-five schedule combined with PTX-24 in these patients were 0.75 mg/m2/d and 135 mg/m2, respectively, with G-CSF support. Although this dose of PTX has significant single-agent activity in ovarian cancer, the dose of TPT is much lower than the TPT dose at which single-agent activity has been observed. Due to the inability to administer near relevant single-agent doses of both drugs in combination, as well as the requirement for G-CSF support, further evaluations of this regimen in women with refractory or recurrent ovarian cancer are necessary before it can be recommended for previously treated patients in this setting.
Living With Treatment Decisions: Regrets and Quality of Life Among Men Treated for Metastatic Prostate Cancer
Authors: Jack A. Clark, Nelda P. Wray, Carol M. Ashton
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To examine variation in men’s long-term regret of treatment decisions, ie, surgical versus chemical castration, for metastatic prostate cancer and its associations with quality of life. METHODS: Survey of previously treated patients to assess treatment decisions and quality of life, supplemented with focus groups. Two items addressing whether a patient wished he could change his mind and the belief that he would have been better off with the treatment not chosen were combined in classifying survey respondents as either satisfied or regretful. χ 2 and t tests were used to test associations between regret and treatment history, complications, and quality of life. RESULTS: Survey respondents included 201 men aged 45 to 93 years (median, 71 years), who had begun treatment (71% chemical castration, 29% orchiectomy) a median of 2 years previously. Most reported complications: hot flashes (70%), nausea (34%), and erectile dysfunction (81%). Most were satisfied with the treatment decision, but 23% expressed regret. Regretful men more frequently reported surgical (43%) versus chemical (36%) castration (P = .030) and nausea in the past week (54% v 32%; P = .010) but less frequently reported erectile dysfunction (56% v 72%; P = .048). Regretful men indicated poorer scores on every measure of generic and prostate cancer–related quality of life. Qualitative analyses revealed substantial uncertainty about the progress of their disease and the quality of the decisions in which patients participated. CONCLUSION: Regret was substantial and associated with treatment choice and quality of life. It may derive from underlying psychosocial distress and problematic communication with physicians when decisions are being reached and over subsequent years.
Detection of diverse SCCmec variants in methicillin-resistant Staphylococcus aureus and comparison of SCCmec typing methods
Authors: J. Kim, J.H. Jeong, H.Y. Cha, J.S. Jin, J.C. Lee, Y.C. Lee, S.Y. Seol, D.T. Cho
Journal: Clinical Microbiology and Infection (2007)
Changes in bronchial mucous membrane depending on the stage of COPD (I, II)
Authors: Tetyana Pertseva, Igor Ivakh, Oxana Plekhanova
Journal: European Respiratory Journal (2011)

Aim: To determinate immune- hystochemical characteristics of bronchial mucous membrane depending on the stage COPD (I, II).

Study population and methods: 78 patients (pts) (mean age 54.2±2.4 years) with COPD were divided on two groups (Gr); Gr I – 32 pts with I stage (22 male), Gr II – 46 pts with II stage (31 male). Bronchoscopy with consequent histology sampling and assessing by microscopy and immunohistochemistry research was done for all pts. The following indexes were evaluated: Ki-67 (reflect proliferative potential and activity of epithelial regeneration); Cytokeratins 8 (Ctk8) (as a marker of glandular epithelium proliferation); 34βE12 expression (for estimation of squamous metaplasia).

Results: Both groups were similar regarding to age, gender and duration of disease. Results of immunihystochemistry present in table 1.

View this table:



In Group I in all pts there were intensive positive membrane reactions with Ctk 8 in ciliary's and basal epithelial cells and absence of reaction with cytokeratin 34βE12. But there were not any microscopically signs of hyperplasia.

In Groupe II all pts took place intensive positive membrane and cytoplasmatic reaction with Ctk 8 in goblet and basal cells with morphologically signs of hyperplasia. Besides, in every sample there were foci with high Ctk 34βE12 expression in basal cells.

Conclusion: 1. Pts with COPD, stage I have significantly higher potential for the bronchial epithelial cells' regeneration in comparison with COPD, stage II. 2. Co-expression of both Ctk 8 and 34βE12 in COPD pts, stage II allows to suppose high risk of irreversible metaplasia in bronchial epithelium.