tbuckley/cabot-search huggingface dataset:
Right Heart Catheterization in Acute Lung Injury
Authors: WILLIAM A. MARINELLI, CRAIG R. WEINERT, CYNTHIA R. GROSS, JOHN P. KNOEDLER, CARON L. BURY, JAMES R. KANGAS, JAMES W. LEATHERMAN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Right heart catheterization (RHC) is commonly used in the diagnosis and management of acute lung injury (ALI). However, controversy exists regarding RHC. We examined RHC use during the first 3 d of ALI in an observational study of 135 patients defined by American–European Consensus Conference criteria. Study parameters examined for association with RHC included the Acute Physiology and Chronic Health Evaluation (APACHE) III score, lung injury score (LIS), and 20 additional epidemiologic, clinical, and laboratory parameters. RHC was performed in 70 patients (52%) within the first 3 d of ALI. RHC was positively associated (p < 0.05) with a diagnosis of sepsis, APACHE III score, blood urea nitrogen (BUN), creatinine, net fluid balance, and positive end-expiratory pressure. RHC was negatively associated (p < 0.05) with mean arterial pressure (Pa) and PaO2 /Fi O2 . Logistic regression identified four predictors for RHC placement: sepsis, PaO2 /Fi O2 , BUN, and Pa. Initial right atrial and pulmonary artery occlusion pressure measurements demonstrated a moderately strong correlation (r = 0.72). Use of RHC was associated with a change in one or more therapeutic interventions (intravascular fluids, vasopressors, diuretics) in 78% of patients. In summary, patients receiving RHC during the first 3 d of ALI were more severely ill than those who did not receive RHC, and RHC was associated with a change in therapy in most patients.
Secalonic Acid-D Represses HIF1α/VEGF-Mediated Angiogenesis by Regulating the Akt/mTOR/p70S6K Signaling Cascade
Authors: Santosh Kumar Guru, Anup Singh Pathania, Suresh Kumar, Deshidi Ramesh, Manjeet Kumar, Satiander Rana, Ajay Kumar, Fayaz Malik, P.R. Sharma, B.K. Chandan, Sundeep Jaglan, J.P. Sharma, Bhahwal Ali Shah, Sheikh Abdullah Tasduq, Surrinder K. Lattoo, Abdul Faruk, A.K. Saxena, R.A. Vishwakarma, Shashi Bhushan
Journal: Cancer Research (2015)

Tumor angiogenesis is a validated target for therapeutic intervention, but agents that are more disease selective are needed. Here, we report the isolation of secalonic acid-D (SAD), a mycotoxin from a novel source that exhibits potent antiangiogenic antitumor activity. SAD inhibited multiple HIF1α/VEGF-arbitrated angiogenesis dynamics as scored in human umbilical vascular endothelial cells and human MCF-7 breast tumor xenografts. Similarly, SAD suppressed VEGF-induced microvessel sprouting from rat aortic ring and blood vessel formation in the Matrigel plug assay in C57/BL6J mice. Under normoxic or hypoxic conditions, SAD inhibited cell survival through the Akt/mTOR/p70S6K pathway, with attendant effects on key proangiogenesis factors, including HIF1α, VEGFR, and MMP-2/MMP-9. These effects were reversed by cotreatment with the Akt inhibitors perifosine and GSK69069 or by the addition of neutralizing VEGF antibodies. The apoptotic properties of SAD were determined to be both extrinsic and intrinsic in nature, whereas the cell-cycle inhibitory effects were mediated by altering the level of key G1-S transition-phase proteins. In experimental mouse models of breast cancer, SAD dosing produced no apparent toxicities (either orally or intraperitoneal) at levels that yielded antitumor effects. Taken together, our findings offered a preclinical validation and mechanistic definition of the antiangiogenic activity of a novel mycotoxin, with potential application as a cancer-selective therapeutic agent.
Chemical Carcinogenesis in the Rat: Common Mode of Action of Carcinogens at the Chromosome Level&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: T Sugiyama, N Ueda, S Maeda, N Shiraishi, K Goto-Mimura, S Murao, S C Chattopadhyay
Journal: JNCI Journal of the National Cancer Institute (1981)

The chromosomal distribution of chromosome aberrations (CA) and sister chromatid exchanges (SCE) induced by various chemical carcinogens such as 7,12-dimethylbenz[a]anthracene, 7,8,12-trimethylbenz[a]anthracene, 1-butyl-1-nitrosourea, urethan, 4-nitroquinoline 1-oxide, 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide, and the antineoplastic compound mitomycin C was studied with the use of noninbred Long-Evans male rat bone marrow cells in vivo and in vitro. The CA and SCE induced by these structurally different chemicals were distributed in a similar pattern among and along chromosomes when the chemicals were given a short time (6 hr) before the metaphase cells were harvested. The specific distribution pattern of chemically induced CA and SCE along chromosomes was attributed to the late DNA replication of the vulnerable chromosome regions. Conversely, X-ray-induced CA were distributed more randomly. Thus the different chemical carcinogens were shown to exert a similar genetic effect at the chromosome level.
Respiratory function in patients with obstructive sleep apnea hypopnea syndrome
Authors: Nadia Boudawara, Leila Boussoffara, Soumaya Bouchareb, Raouia Ouaja, Habib Khalil, Mounira Sakka, Jalel Knani
Journal: European Respiratory Journal (2014)

Introduction:  In the obstructive apnea hypopnea syndrome Sleep (OSAHS) the exploration of respiratory function is indicated for smoking subjects and / or ex -smoking subjects with lung disease associated and cases of obesity with BMI ≥ 30.  The aim of our study was to investigate disorders of respiratory function related to OSAHS.   Patients and methods : We performed pulmonary function tests (plethysmography, arterial blood gas and 6 minute walk test) for all patients aged over 18 years and who having a suspicion of OSAHS. We included all patients with OSAHS  (AHI / h ≥ 5) after recording polygraphy. We excluded patients with pulmonary pathology associated other than OSAHS.   Results:  468 patients presented in pulmonology department of CHU Taher Sfar Mahdia for exploration of a sleep apnea syndrome, among them only 218 patients were enrolled. OSAHS was mild in 25 % of cases, moderate in 23% of cases and severe in 52 % of cases. An obstructive ventilatory defect was found in 28 % of cases. A restrictive ventilatory defect in 30 % of cases. Neither the severity of OSAHS, nor the BMI did not influence the presence of a certain type of ventilatory defect.   Conclusion:  OSAHS may be accompanied by a ventilatory deficit. A pulmonary function study is needed with different parameters of ventilation, and on a larger scale.
Acute Ischemic Stroke Therapy
Authors: Louis R. Caplan, Anthony J. Furlan, Werner Hacke
Journal: JAMA Neurology (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Cohort study of patients with asthma and immunodeficiency
Authors: Mayra Parra Pérez, Marta Ferrer Galván, Verónica Sánchez López, Auxiliadora Romero Falcón, Juan Francisco Medina Gallardo, Pilar Pérez Morilla, Pablo Pérez Navarro, Francisco Javier Álvarez Gutierrez
Journal: European Respiratory Journal (2014)

Background: The relation between bronchial asthma and immunodeficiency has been described previously. Associated are deficits of IgG subclasses and MBL (Mannose Binding Lectin). These patients can present with severe asthma due to repeated respiratory infections.  Aims: We describe the clinical and functional profiles of patients with asthma and immunodeficiency and their respective type of deficit.  Methods: We included 76 adult patients diagnosed with bronchial asthma according to GINA criteria (Global Initiative for Asthma) and immunodeficiency (with immunological tests). We evaluated: Grade of control, atopy, severeness of asthma, number of exacerbations in previous year. We found the most frequent types of immunodeficiency and their differences.  Results: Mean age was 63 (±8) years, 78% (59) female, non-smokers: 83 %( 63), atopy 45%(34). Severe Asthma: 64% (49). Moderate Asthma: 24% (18). Mild Asthma: 12%(9). Fully controlled: 52% (40). Partly controlled: 20% (15). Uncontrolled: 28 %( 21). Number of exacerbations in previous year: 2 (±2). Most frequent type of immunodeficiency was MBL with 63% (48), in 31 % of patients (15) associated with a deficit of IgG1. Subclasses: Deficit of IgG1: 32% (24), IgG4 in 11% (8), deficits in more than one subtype of IgG 14,5% (11). Patients with shortages of both MBL and IgG1 had more exacerbations 5 (±2) and presented severe asthma in 80% (12) and uncontrolled asthma in 67% (10).   Conclusions:  We found association between immunodeficiency and asthma in an ample group of patients, the most common deficit was MBL. The patients with deficits of both MBL and IgG1 presented with the most severe symptoms. Immunological studies in patients with asthma and frequent exacerbations are needed.
BMA demands that health services be excluded from trade treaty
Authors: G. Iacobucci
Journal: BMJ (2015)

The BMA has urged the four UK governments to remove health and social care services and public health legislation from the controversial trade deal currently being negotiated between the European Union and the United States.

In a motion overwhelmingly carried at the BMA’s annual representative meeting in Liverpool this week, doctors expressed concern that the Transatlantic Trade and Investment Partnership (TTIP) posed a …
Enhanced expression of IL-18 receptor but not soluble form of IL18R in chronic obstructive pulmonary disease (COPD)
Authors: Shinichi Takenaka, Tomoaki Hoshino, Yuki Sakazaki, Masanori Sawada, Hanako Oda, Haruki Imaoka, Satoko Takei, Takashi Kinoshita, Tomotaka Kawayama, Hisamichi Aizawa
Journal: European Respiratory Journal (2011)

We have recently reported that a significant correlation exists between serum levels of IL-18 and pulmonary functions in COPD patients (Imaoka, ERJ 2008). These results suggest that IL-18R expression can be over-expressed in the lungs of COPD. More recently, we isolated and characterized the soluble human IL-18Ra complex (sIL-18Ra) from human serum. We also found that serum levels of the complex in RA patients were significantly higher than in healthy controls (submitting). In this study, we examined whether the expression of IL-18Ra proteins is increased in the lungs obtained from very severe COPD patients who underwent for lung volume reduction surgery. We also examined the serum levels of sIL-18Ra in non-smokers, smokers and COPD patients. We used immunohistochemical techniques to examine the expression of IL-18Ra in the lungs of very severe COPD (GOLD Stage IV) (n = 16), smokers (n = 13), and non-smokers (n = 13). IL-18Ra proteins were strongly expressed especially in alveolar macrophages, mononuclear cells, and both the bronchiolar and alveolar epithelia in the lungs of COPD, but not smokers nor non-smokers. Interestingly, serum levels of sIL-18Ra in 100 COPD (GOLD stage I [n=28], II [n=34], III [n=22], and IV [n=16]), 36 smokers and 51 non-smokers were 41.6±8.1, 53.1±17.5, and 58.6±11.8 ng/ml, respectively. Interestingly,serum levels of sIL-18Ra in COPD (n=100) were significantly (P
Induction and Transplantation of Murine Skin Cancers Induced by Methoxsalen Plus Ultraviolet (320–400 nm) Radiation&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: M L Kripke, W L Morison, J A Parrish
Journal: JNCI Journal of the National Cancer Institute (1982)

Properties of skin tumors resulting from treatment of mice with ip methoxsalen plus UVA (320-400 nm) radiation (PUVA) were compared to those of skin tumors induced by UVB (280-320 nm) radiation. Repeated treatment of C3H/HeN murine mammary tumor virus-negative (C3H-) mice with PUVA produced both fibrosarcomas and squamous carcinomas that were indistinguishable morphologically from UVB-induced tumors. Fragments of 12 primary PUVA-induced tumors were transplanted into normal and immunosuppressed syngeneic recipients, and all grew progressively. In contrast, 19 primary tumors induced by repeated exposure of C3H- mice to UVB grew only in the immunosuppressed mice and not in the normal recipients. The growth of graded doses of cells from 5 PUVA-induced tumors was compared in normal and UVB-irradiated recipients. No preferential growth in UVB-irradiated mice was observed, even though this is characteristic of UVB-induced tumors. Thus PUVA-induced tumors do not appear to have the same antigenic properties as UVB-induced tumors.
Effect of heart-lung transplantation on airway potential difference in patients with and without cystic fibrosis
Authors: EW Alton, A Khagani, RF Taylor, R Logan-Sinclair, M Yacoub, DM Geddes
Journal: European Respiratory Journal (1991)

Measurement of the potential difference (PD) across the airways provides an indication of the viability and integrity of the lining epithelium. PD was recorded from the lower airways in "diseased controls" and in patients following heart-lung transplantation. Diseased controls showed a high PD centrally which fell (became less negative) peripherally (trachea -15.8 mV (SEM 1.0), lobar bronchi -12.6 mV (1.2), segmental bronchi -9.8 mV (1.2]. Following heart-lung transplantation (HLT) the profile of PD with airway size was altered in comparison to non-transplanted patients with reduced values in the large airways. Host tracheal values above the anastomosis were similarly reduced. Two episodes of rejection were associated with a lower mean airway PD; no significant changes were found with infection. In patients with cystic fibrosis (CF), values in the donor lung did not differ from those in non-CF transplanted patients up to one year following transplantation, although nasal PD in the host remained elevated. HLT selectively alters the PD profile only of larger airways, which may relate to the interruption of the bronchial arterial supply to these sites.
Granulocyte colony-stimulating factor in established febrile neutropenia: a randomized study of pediatric patients.
Authors: P L Mitchell, B Morland, M C Stevens, G Dick, D Easlea, L C Meyer, C R Pinkerton
Journal: Journal of Clinical Oncology (1997)

PURPOSE Infection in neutropenic patients is potentially life-threatening and carries important implications for hospital resource use. Prophylactic administration of cytokines may reduce the severity of neutropenia, but involves the treatment of all patients for the possible benefit of a minority. This study evaluates whether treatment with cytokines in the setting of established febrile neutropenia will influence outcome and be potentially more cost-effective. PATIENTS AND METHODS In a double-blind study, pediatric patients with fever and severe neutropenia were randomized to receive granulocyte colony-stimulating factor ([G-CSF] filgrastim; 5 microg/kg/d) or placebo, in addition to antibiotics. The study protocol required a resolution of fever and a neutrophil count &gt; or = 0.2 x 10(9)/L for hospital discharge. Patients could be randomized for up to four independent febrile episodes. A total of 186 episodes of febrile neutropenia were investigated. RESULTS Patients randomized to G-CSF had a shorter hospital stay (median, 5 v 7 days; P = .04) and fewer days of antibiotic use (median, 5 v 6 days; P = .02). G-CSF-treated patients also had more rapid neutrophil recovery and higher neutrophil levels at discharge. The 2-day reduction in hospital stay reduced the median bed cost by 29% per patient admission (P = .04). CONCLUSION Under the clinical guidelines of our institution, the use of G-CSF in the treatment of established febrile neutropenia produced a small but significant reduction in the time that children required antibiotics and hospital admission, with possible cost savings.
Treatment-related leukemia in breast cancer patients treated with fluorouracil-doxorubicin-cyclophosphamide combination adjuvant chemotherapy: the University of Texas M.D. Anderson Cancer Center experience.
Authors: E Diamandidou, A U Buzdar, T L Smith, D Frye, M Witjaksono, G N Hortobagyi
Journal: Journal of Clinical Oncology (1996)

PURPOSE Adjuvant chemotherapy for breast cancer has been the routine practice in the past decade. A number of studies have observed an increased incidence of treatment-related leukemias following chemotherapy with alkylating agents and/or topoisomerase II inhibitors. We evaluated the incidence of treatment-related leukemias in breast cancer patients treated in four adjuvant and two neoadjuvant chemotherapy trials at The University of Texas M.D. Anderson Cancer Center. PATIENTS AND METHODS Between 1974 and 1989, 1,474 patients with stage II or III breast cancer were treated in six prospective trials of adjuvant (n = 4) or neoadjuvant (n = 2) chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide (CTX) (FAC) with or without other drugs. The median observation time was 97 months. In 1,107 patients, FAC chemotherapy was given postoperatively; 367 patients received induction chemotherapy, as well as postoperative chemotherapy. Eight hundred ten patients had surgery followed by radiotherapy and chemotherapy; 664 patients had surgery and chemotherapy only. Patients in two adjuvant and one neoadjuvant study received higher cumulative doses of CTX compared with those in the other studies. RESULTS Fourteen cases of leukemia were observed. Twelve of these patients had received radiotherapy and chemotherapy, and two had received chemotherapy only. Six of the reported patients with leukemia were treated with a cumulative CTX dose of greater than 6 g/ m2. Five of these patients had received both radiotherapy and chemotherapy. The median latency period in the 14 patients was 66 months (range, 22 to 113). Six of 10 patients with adequate cytogenetic analyses had abnormalities that involved chromosomes 5 and/or 7. The rest of the patients had nonspecific cytogenetic abnormalities or lacked cytogenetic information. The 10-year estimated leukemia rate was 1.5% (95% confidence interval [CI], 0.7% to 2.9%) for all patients treated, 2.5% (95% CI, 1.0% to 5.1%) for the radiotherapy-plus-chemotherapy group, and 0.5% (95% CI, 0.1% to 2.4%) for the chemotherapy-only group; this difference was statistically significant (P = .01). The 10-year estimated leukemia risk for the higher-dose (&gt; 6 g/m2) CTX group was 2% (95% CI, 0.5% to 5.0%) compared with 1.3% (95% CI, 0.4% to 3.0%) for the lower-dose group, a difference that was not statistically significant (P = .53). CONCLUSION These data illustrate that patients treated with adjuvant FAC chemotherapy plus radiotherapy have a slightly increased risk of leukemia. This information needs to be considered in the treatment plans for patients with breast cancer. However, for most patients, the benefits of adjuvant therapy exceed the risk of treatment-related leukemia.
<i>EWS-FLI1</i> and <i>EWS-ERG</i> Gene Fusions Are Associated With Similar Clinical Phenotypes in Ewing's Sarcoma
Authors: Jill P. Ginsberg, Enrique de Alava, Marc Ladanyi, Leonard H. Wexler, Heinrich Kovar, Michael Paulussen, Andreas Zoubek, Barbara Dockhorn-Dworniczak, Herbert Juergens, Jay S. Wunder, Irene L. Andrulis, Rajesh Malik, Poul H.B. Sorensen, Richard B. Womer, Frederic G. Barr
Journal: Journal of Clinical Oncology (1999)

PURPOSE: There are a variety of solid tumors in which alternative chromosomal translocations generate related fusion products. In alveolar rhabdomyosarcoma and synovial sarcoma, these variant fusions have been found to have major clinical significance. We investigated whether the two alternative gene fusion products, EWS-FLI1 and EWS-ERG, define different clinical subsets within the Ewing's sarcoma family of tumors. PATIENTS AND METHODS: We selected 30 cases of Ewing's sarcoma with the EWS-ERG gene fusion and 106 cases with the EWS-FLI1 fusion. Clinical data were obtained for each case and compared with the molecular diagnostic findings. RESULTS: There were no significant clinical differences observed between the two groups in age of diagnosis, sex, metastasis at diagnosis, primary site, event-free survival, or overall survival. CONCLUSION: Differences in the C-terminal partner in the Ewing's sarcoma family gene fusions are not associated with significant phenotypic differences.
SPC2968—A novel Hif-1α antagonist for treatment of clear cell renal cell carcinoma
Authors: M. Westergaard, H. F. Hansen, C. A. Thrue, J. B. Hansen, L. S. Kjaerulff, E. M. Straarup, O. Olsen, L. W. Dalby, L. Hildebrandt-Eriksen, P. Kearney
Journal: Journal of Clinical Oncology (2006)

14581 Background: SPC2968 is a short (16-mer), oligonucleotide antagonist of Hif-1α mRNA in which potency has been enhanced through incorporation of Locked Nucleic Acid. Over-expression of Hif-1α has been correlated with increased vascularisation, metastatic potential and poor clinical outcome in a variety of malignancies, including Renal Cell Carcinoma (RCC) of clear cell aetiology, where Hif-1α dysregulation, brought about by mutations in the von Hippel Lindau gene, appears to play a major pathogenic role. Methods: In vitro, human cancer and endothelial cells grown under hypoxic conditions were used to evaluate the effect of SPC2968 on mRNA and protein to Hif-1α as well as phenotypic effects, measured by quantitative polymerase chain reaction (QPCR), Western blotting and biochemical/cellular assays. QPCR was also used to measure mRNA levels in SPC2968-treated mice, while the effects of the drug on tumour growth and vascularisation were evaluated in xenografts. To assess biodistribution in vivo, tritium-labelled SPC2968 was injected intravenously. Results: In vitro, SPC2968 at 1nM reduced both mRNA and protein levels of Hif-1α in cancer cell lines and downregulated two downstream targets of Hif-1, VEGF and MMP-2.Treatment also induced apoptosis in tumour cells and prevented tube formation by endothelial cells in vitro. Parenteral administration of SPC2968 in mice yielded potent inhibition of Hif-1α and VEGF mRNA in several tissues, including kidney, liver, and colon. Radioactively labelled SPC2968 distributed to kidney, liver, colon, bone marrow, lymph nodes and skin. Preclinical studies investigating acute and sub-acute toxicity and safety pharmacology of SPC2968 are completed, and SPC2968 was well tolerated. Conclusions: SPC2968 is an effective suppressor of Hif-1α mRNA and Hif-1α-regulated genes in vitro and in vivo and has shown good tissue biostability and biodistribution in rodents. Preclinical safety studies have been completed, and SPC2968 is ready for clinical testing. A phase I/II, dose-escalating study of SPC2968 in clear cell RCC in the US and the EU is planned to be submitted by mid 2006. [Table: see text]
Definitions, methodology and therapeutic strategies in portal hypertension
Authors: R. de Franchis, J.P. Pascal, E. Ancona, A.K. Burroughs, M. Henderson, W. Fleig, R. Groszmann, J. Bosch, T. Sauerbruch, C. Soederlund, D. Lebrec, T.I.A. Soerensen, L. Pagliaro
Journal: Journal of Hepatology (1992)