tbuckley/cabot-search huggingface dataset:
Low-dose ACOP-B and VABE: weekly chemotherapy for elderly patients with advanced-stage diffuse large-cell lymphoma.
Authors: S E O'Reilly, P Klimo, J M Connors
Journal: Journal of Clinical Oncology (1991)

Elderly patients with advanced-stage diffuse large-cell lymphomas (DLCLs) are either excluded from or under-represented in most clinical trials of combination chemotherapy regimens because they tolerate treatment poorly and usually have a worse outcome. We report two brief weekly chemotherapy regimens designed specifically for elderly patients. Eligible patients were aged 65 to 85 years, had advanced-stage DLCL (diffuse mixed, diffuse large-cleaved or noncleaved, immunoblastic, or diffuse large-cell not otherwise specified). Advanced stage was defined as Ann Arbor stage III or IV or stage I or II with a mass greater than 10 cm or B symptoms. Low-dose doxorubicin, cyclophosphamide, vincristine, bleomycin, and prednisone (LD-ACOP-B) accrued 40 patients between March 1983 and September 1985; 65% achieved a complete response (CR), there were two toxic deaths, the actuarial failure-free survival (FFS) is 19%, disease-specific survival (DSS) 30%, and overall survival (OS) 28%, with a maximum follow-up of 6 years. The regimen of etoposide, doxorubicin, vincristine, bleomycin, and prednisone (VABE) accrued 32 patients between July 1985 and June 1987; 63% achieved a CR, there were two toxic deaths, and the actuarial FFS is 34%, DSS 45%, and OS 36%, with a maximum follow-up of 4 years. There is no difference in FFS, DSS, or OS between these two regimens. VABE caused more myelosuppression and infectious complications, although the toxic death rates were similar. We prefer LD-ACOP-B because follow-up is longer and toxicity is less.
Abstract 17594: Brain Microglial Cytokines are Critical for Renin-Angiotensin-Aldoterone-System(RAAS)-Induced Neurogenic Hypertension
Authors: Peng Shi, Justin L Grobe, Fiona A Desland, Vermali Rodriguez, Zhiying Shan, Elaine M Richards, Mohan K Raizada, Colin Sumners
Journal: Circulation (2011)

Purpose: Our previous studies have established that activation of microglial cells and production of proinflammatory cytokines (PIC) within the PVN are two critical events in the establishment of chronic angiotensin (Ang) II-induced neurogenic hypertension. These have led us to hypothesize that brain microglial cells are a primary target of Ang II, initiating a sequence of cellular and physiological events resulting in sympathetic nervous system activation and hypertension. Methods: Microglial cells from the hypothalamus of Sprague-Dawley rats were established in primary culture. Their phenotype was confirmed by the presence of IBa1 immunoreactivity and high levels of CD11b mRNA, markers for microglia. They were used to determine the effects of, Ang II, prorenin and aldosterone (ALDO) on cytokine production. Neurogenic hypertensive mice were generated using decoxycorticosterone acetate (DOCA)-salt model (DOCA 50 mg s.c., 0.15 M NaCl in drinking water for 3 weeks). The PVN was dissected to determine PIC expression at the end of the protocol. Results: Treatment of cultures with Ang II (100 nM) or ALDO (1 nM) for 24 hr increased the expression of PIC mRNAs, e.g. for tumor necrosis factor (TNF)α. Ang II and ALDO elicited respective 2- and 3-fold increases (P&lt;0.05). More strikingly, we found that prorenin (20 nM, 24 hr) elicited highly significant 300- and 400-fold increases in the expression of TNFα and interleukin (IL)-1β mRNAs, respectively (P&lt;0.05). These effects of prorenin were associated with respective 16- and 14-fold increases in NFκb1 and NFκbia mRNA levels, which are two subunits of the transcription factor NFκb complex. We previously demonstrated that DOCA mice exhibit a similar hypertensive phenotype as double transgenic hypertensive sRA mice, which display increased levels of PIC and activation of microglia in the PVN. Consistently, DOCA-salt mice exhibit respective 1.5, 1.08 and 1.09 fold increases in the expression of mRNAs for IL-1β, TNFα and IL-6 in the PVN compared to control mice (n=3-4). Conclusion: These data indicate that brain microglial cells are the primary target of RAAS components in promoting PIC production, which in turn contribute to hypertension development.
Radiologic manifestations of patients with H1N1 infection
Authors: Mehrdad Bakhshayesh, Bahare Saidi, Payam Tabarsi, Soheyla Zahirifard
Journal: European Respiratory Journal (2011)

Purpose: Swine flu influenza is a very contagious respiratory infection and WHO has raised the alert level to phase 6 (pandemic). The aim of this study was to evaluate the chest X-ray and CT scan of patients with documented influenza A (H1N1) virus infection

Material and methods: 31patients (16 men and 15 women), with H1N1infection confirmed by RT-PCR were included. 31 patients had available chest X-rays and of these 10 had CT scans. The initial radiography obtained from the patients was reviewed regarding pattern (consolidation, ground glass, nodules and reticulation), the distribution (focal, multifocal, and diffuse) and the lung zones involved. CT scans were also reviewed for the same abnormalities. The patient files were studied. LDH and CPK level was available for 22 and 24 patients respectively.

Results: The mean age was 37.97±13.9 years. 17 (54.8%) patients had Co-existing condition (8 Respiratory, 5 cardiovascular, 2 Immunodeficiency, 2 Cancer, 4 others). 12 (38.7%) patients required ICU admission. 5 (16.1%) patients died.8 (25.8%) had normal initial radiographs. The most common radiographic abnormality was consolidation (12/31; 38.7%) in the peripheral region (11/31; 35.5%) followed by peribronchovascular (10/31; 32.3%) which was most commonly observed in the lower zone (left 61.3%; right 45.2%). The patients admitted to the ICU were more likely to have two or more lung zones involved (p =0.005). 11 (35.5%) patients had pleural thickening or effusion.

Conclusion: In patients with the novel swine flu the most common radiographic abnormality observed in our center was consolidation in the lower lung zones. Patients admitted to ICU were more likely to have two or more lung zones involved.
An audit to assess the value of the MDT approach in patients in a UK CF unit
Authors: Manish Gautam, Abdul Ashish, Martin Ledson, Josheel Naveed, Martin Walshaw
Journal: European Respiratory Journal (2011)

Background: It is widely accepted that in CF best patient and family care should involve a well co-ordinated multidisciplinary service. However, the interdisciplinary effectiveness of the team, including the patient's perception of their team is rarely assessed.

Aims: We performed this study in order to evaluate the performance of our local CF MDT from an objective and patient perspective.

Methods: “On the spot” questionnaires were distributed to MDT members, who had worked with the unit for over one year. Questions were related to the knowledge of 15 randomly selected CF patients regarding their microbiology, FEV1, transplant status, social history, portacath, compliance issues and insulin therapy.

Results: 

View this table:

Table 1. Knowledge of MDT members about their patients





Questionnaires were simultaneously distributed to the same patients for anonymous completion requiring them to rank the MDT members according to perceived importance in their care and their relationship with each.

View this table:

Table 2. Overall ranking by patients





Conclusions: Results confirmed CF patients often form close rapport with specialist nurses and associate Consultants with important decision making related to their care. Interestingly, doctors and CF nurses scored equally well in patient knowledge and only marginally above others. These results suggest an effectively functioning MDT whilst highlighting the often under-recognised value of individual specialities.
Intestinal Folate Absorption
Authors: Edward J. Olinger, Joseph R. Bertino, Henry J. Binder
Journal: Journal of Clinical Investigation (1973)

These studies were designed to determine whether pteroylmonoglutamic acid (PGA) at physiologic concentrations is transported across the small intestine unaltered or is reduced and methylated to the circulating folate form (5-methyltetrahydrofolate [5-MeFH(4)]) during absorption. [(3)H]PGA was incubated in vitro on the mucosal side of rat jejunum. Of the folate transferred to the serosal side, the percent identified as 5-MeFH(4) by DEAE-Sephadex chromtography was inversely related to the initial mucosa PGA concentration: at 7, 20, and 2,000 nM, 44%, 34%, and 2%, respectively, was converted to 5-MeFH(4). In contrast, less than 4% of the folate transferred across ileal mucosa was 5-MeFH(4) when the initial mucosa concentration was 20 nM. Specific activity of dihydrofolate (DHF) reductase, the enzyme responsible for converting PGA to tetrahydrofolic acid, was measured in villus homogenates and was significantly greater in the jejunum than in the ileum. 1,000 nM methotrexate (MTX), a DHF reductase inhibitor, markedly inhibited PGA conversion to 5-MeFH(4) by the jejunum. Studies of transmural flux, initial rate of mucosal entry (influx) and mucosal accumulation (uptake) of folate were also performed. Although MTX did not alter the influx of PGA, MTX decreased jejunal mucosal uptake but increased transmural movement. Transmural folate movement across ileal mucosa was greater than across jejunal mucosa although mucosal uptake was greater in the jejunum than in the ileum. These results could explain previous studies which have failed to identify conversion of PGA to 5-MeFH(4) when intestinal preparations have been exposed to higher and less physiologic concentrations of PGA. Further, these studies suggest that 5-MeFH(4) may be retained by the jejunal mucosa.
Comprehensive Analysis of Serum Biomarker and Tumor Gene Mutation Associated with Clinical Outcomes in the Phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (Select)
Authors: M. Tahara, M. Schlumberger, L.J. Wirth, R. Elisei, M. Brose, M.A. Habra, K. Newbold, N. Kiyota, C. Dutcus, J. Zhu, T. Kadowaki, Y. Funahashi, B. Robinson, S. Sherman
Journal: Annals of Oncology (2014)
Trends in Cancer Risks Among Swedish Agricultural Workers2
Authors: Kerstin Wiklund, Lars-Erik Holm
Journal: JNCI Journal of the National Cancer Institute (1986)

Journal Article Trends in Cancer Risks Among Swedish Agricultural Workers Get access Kerstin Wiklund, Kerstin Wiklund Search for other works by this author on: Oxford Academic PubMed Google Scholar Lars-Erik Holm Lars-Erik Holm Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 77, Issue 3, September 1986, Pages 657–664, https://doi.org/10.1093/jnci/77.3.657 Published: 01 September 1986 Article history Received: 16 October 1985 Accepted: 10 April 1986 Published: 01 September 1986
Acute respiratory distress syndrome in patients with and without diffuse alveolar damage: an autopsy study
Authors: José A Lorente, Pablo Cardinal-Fernández, Diego Muñoz, Fernando Frutos-Vivar, Arnaud W Thille, Carlos Jaramillo, Aida Ballén-Barragán, José M Rodríguez, Oscar Peñuelas, Guillermo Ortiz, José Blanco, Bruno Valle Pinheiro, Nicolás Nin, María del Carmen Marin, Andrés Esteban, Taylor B Thompson
Journal: Intensive Care Medicine (2015)
Upper airway evaluation by drug-induced sleep endoscopy (DISE) in children with Down syndrome and obstructive sleep apnoea
Authors: Mieke Maris, Stijn Verhulst, Marek Wojciechowski, Vera Saldien, Paul Van de Heyning, An Boudewyns
Journal: European Respiratory Journal (2013)

Introduction: The statement that upper airway obstruction during sleep in children with Down Syndrome (DS) is caused by a large tongue falling backwards, has recently been challenged. Imaging studies have shown that DS is characterised by a narrow upper airway and relative macroglossia.  Aim: To investigate the pattern of upper airway obstruction in children with DS and obstructive sleep apnoea (OSA).  Methods: Fifteen DS children with OSA, age 4.0 ± 3.9 years, BMI 17.5 ± 4.1 kg/m2 and OAHI 17.5 ± 18.4/hr, without previous upper airway surgery underwent an upper airway endoscopy during drug-induced sleep (DISE). The upper airway was examined under spontaneous breathing and the site (s) of upper airway obstruction or hypotonia were documented.  Results: Significant obstruction at the level of adenoids and/or tonsils was found in 13 out of 15 patients. The remaining 2 patients showed upper airway hypotonia. Partial obstruction at the level of the tongue base was documented in 1 patient with concomittant adenotonsillar obstruction. Obstruction at the level of the epiglottis was found in 6 subjects.  Conclusions: Upper airway evaluation with drug-induced sleep endoscopy in surgically naive Down syndrome children with OSA showed that adenotonsillar hypertrophy is the major cause of upper airway obstruction. Obstruction at the level of the epiglottis was more commonly observed than in otherwise healthy children with OSA and illustrates that DS children may have multilevel upper airway collapse.  Only 1 out of 15 patients had a tongue base obstruction supporting the concept of “ relative macroglossia”.
Breast Cancer Tumor Suppressors: A Special Emphasis on Novel Protein Nischarin
Authors: Mazvita Maziveyi, Suresh K. Alahari
Journal: Cancer Research (2015)

Abstract Tumor suppressor genes regulate cell growth and prevent spontaneous proliferation that could lead to aberrant tissue function. Deletions and mutations of these genes typically lead to progression through the cell-cycle checkpoints, as well as increased cell migration. Studies of these proteins are important as they may provide potential treatments for breast cancers. In this review, we discuss a comprehensive overview on Nischarin, a novel protein discovered by our laboratory. Nischarin, or imidazoline receptor antisera-selected protein, is a protein involved in a vast number of cellular processes, including neuronal protection and hypotension. The NISCH promoter experiences hypermethylation in several cancers, whereas some highly aggressive breast cancer cells exhibit genomic loss of the NISCH locus. Furthermore, we discuss data illustrating a novel role of Nischarin as a tumor suppressor in breast cancer. Analysis of this new paradigm may shed light on various clinical questions. Finally, the therapeutic potential of Nischarin is discussed. Cancer Res; 75(20); 4252–9. ©2015 AACR.
Extrahepatic Bile Duct Carcinoma: Role of the p53 Protein Family
Authors: Alexander I. Zaika, Seung-Mo Hong
Journal: Liver Cancer (2009)

Bile duct carcinomas (cholangiocarci-noma) are devastating tumors. Surgical resection is the mainstay of current treatment; however, it is only effective for a limited number of patients diagnosed at early stages of the disease. Unfortunately, the vast majority of patients seek treatment of the advanced disease making them poor candidates for curative surgery. Conventional chemotherapy and radiation therapy have not been shown to be effective in prolonging long-term survival of patients with cholangiocarcinoma. In addition, there are no sensitive and specific tests to diagnose and exclude this disease in high-risk populations. Thus, there is an urgent need for novel biomarkers and therapies based on a better understanding of biliary tumorigenesis that would significantly impact the disease outcome. This chapter reviews current clinical data on the p53 protein family and its role in biliary tumorigenesis.
T cell CRAC dependence
Authors: Nicole Johnston
Journal: The Journal of Experimental Medicine (2005)

Calcium transport is critical for the activation of transcription pathways that drive T cell proliferation and function. On page 651, Feske and colleagues show that Ca2+ release–activated Ca2+ (CRAC) channels in the plasma membrane are the major, if not only, pathway for T cell receptor–activated calcium influx in T cells. The mechanism of activation and identity of these CRAC channels continues to elude researchers.

The authors analyzed channels in T cells from patients with a form of severe congenital immunodeficiency (SCID) that is characterized by impaired T cell activation and a near total lack of calcium influx. Using electrophysiological techniques, they showed that the lack of calcium influx was due to a complete failure of CRAC channel opening, and not a consequence of dysregulated intracellular calcium stores or aberrant expression of other suspected ion channels. The authors believe that the CRAC channels are present in the patients' T cells but that their activation is somehow impaired.

The specificity and severity of the defect in T cells from the SCID patients provide a powerful tool to pinpoint the identity of the CRAC channel and determine its mode of activation. The authors are now using positional cloning approaches and genetic complementation to try to isolate the underlying molecular components.
Inhalation challenge in pigeon breeder's disease: BAL fluid changes after 6 hours
Authors: SP Reynolds, KP Jones, JH Edwards, BH Davies
Journal: European Respiratory Journal (1993)

The purpose of this study was to determine the cellular events occurring 6 h after bronchial inhalation challenge, in a group of pigeon breeders. Twelve subjects agreed to undergo challenge, either with nebulized pigeon serum (Ps) (n = 10), or with saline (n = 2). The development of characteristic symptoms was used to detect a positive response in combination with monitoring tests (white blood cell count (WBC), body temperature, and spirometry). An initial bronchoalveolar lavage (BAL) was performed before inhalation challenge, and a further BAL on the previously spared right middle lobe subsegment or lingula 6 h after challenge. Paired bronchoalveolar lavage fluid (BALF) samples were analysed for urea, albumin, total and differential WBC, interleukin-1 and interleukin-2. There was a significant increase in total cells, lymphocytes, T-lymphocytes, and neutrophils; numbers.ml-1 of BALF in responders. A monitoring score reflecting severity of patient response correlated with an increase in all cell types (p &lt; 0.05). In conclusion, responders developed both a BALF lymphocytic and neutrophilic "alveolitis" following inhalation challenge, the degree of BALF "alveolitis" correlating with the severity of patient response.
One year survival differences of EGFR- and KRAS-mutated advanced non-small cell lung cancer (NSCLC) compared to the wildtype population
Authors: Christian Boch, Jens Kollmeier, Andreas Roth, Daniel Misch, Anna Streubel, Thomas Mairinger, Torsten T. Bauer
Journal: European Respiratory Journal (2012)

Introduction: With investigation of the complex relationship between EGFR-related biomarkers and response to tyrosine kinase inhibitor (TKI) novel therapies for NSCLC have been established. In numerous clinical studies the effect of TKIs in patients with activating EGFR mutations is proven by a better progression free survival (PFS) while the prognostic value of KRAS mutations remain vague. The current study in our clinic retrospectively analysed the one year survival of patients with NSCLC and an activating EGFR- or KRAS-mutation.  Methods: Within 15 months until Dec 2010, all subsequent biopsies of newly diagnosed NSCLC (n=753) were tested for the ability to be analysed by Sanger- and Pyrosequencing for the presence of EGFR mutations and by LightCycler Real-time PCR for the presence of KRAS mutations. The obtained data were correlated with the centre-bound tumour registry for survival data and analysed by Kaplan-Meier estimator.  Results: In a total of 552 cases with NSCLC, EGFR mutation was present in 27/552 (4,9%, male n=10) and KRAS mutation in 85/552 cases (15,8%, male n=43). In advanced NSCLC (IIIB/IV), 16/27 patients had an EGFR mutation and 46/85 had KRAS mutation. The one year survival of advanced NSCLC and EGFR mutation was 11/16 (68,8%) vs. 5/16 (31,3%) without mutation. Stratifying according to KRAS it was 15/46 (34,8%) with vs. 30/46 (65,2%) without mutation.  Conclusion: Comparable with previous reports, the one year survival of NSCLC with EGFR mutation is improved whereas the the one year survival with KRAS mutations seems to be poorer.
A 66-Year-Old Woman With Newly Diagnosed Oligometastatic Non–Small Cell Lung Cancer
Authors: Stacey Shiovitz, Keith D. Eaton
Journal: Journal of the National Comprehensive Cancer Network (2012)

A 66-year-old woman presented with newly diagnosed stage IV non-small cell lung cancer (NSCLC) and a large adrenal metastasis. She initially had flu-like symptoms and dyspnea and was found to have a right upper lobe (RUL) lung nodule. Chest CT showed a 1.4-cm spiculated RUL lung nodule, peripheral right lung nodule, right perihilar mass, and 10.9-cm left adrenal mass. PET/CT showed enhancement of the RUL nodule, hilar mass, and left adrenal mass. She presented for evaluation of treatment options. This case was thought to represent an instance of oligometastatic stage IV NSCLC. Literature suggests that a select patient population with otherwise resectable disease may benefit from surgical resection of a lung primary and the isolated metastasis with improved survival. This seems to be most effective in patients who have undergone a complete staging evaluation with PET scan; CT of the chest, abdomen, and pelvis; and a brain MRI revealing T1-2, N0-1, M-oligo disease. This radical approach should be reserved for patients with potentially curative disease based on the staging evaluation and who are otherwise good surgical candidates.
Induction of Endogenous Mammary Tumor Virus Expression During Hormonal Induction of Mammary Adenoacanthomas and Carcinomas of BALB/c Female Mice&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: C M McGrath, W A Prass, T M Maloney, R F Jones
Journal: JNCI Journal of the National Cancer Institute (1981)

Treatment of BALB/c female mice with pituitary isografts, under conditions that established mammary hyperplasia in an anovulatory condition, enhanced mammary tumor development with prior onset of dysplastic foci in lobular parenchyma. Tumor onset began at 8 months (mean onset time, 18 mo); the 25-month incidence was 100%. Adenoacanthomatous tumors appeared first. Adenocarcinomas appeared only after more than 14 months of continuous hormone stimulation. Dysplastic and neoplastic changes occurred while blood levels of the three major mammotropic hormones were physiologic. Murine mammary tumor virus (MuMTV) p28 was detected in all tumors tested, independent of time of tumor appearance or tumor type, although keratinizing cells in adenoacanthomatous tumors did not contribute to MuMTV antigen expression. MuMTV gp52 was detected in only a small fraction of cells in a few tumors. MuMTV RNA contents were above normal in all tumors tested. Neither MuMTV structural antigens nor RNA was induced in normal glands by the same hormone treatment that ultimately resulted in dysplasia and tumor formation and elevated levels of these viral markers in neoplasms. The MuMTV RNA in all hormone-induced tumors was readily distinguishable in base sequence from standard MuMTV RNA but indistinguishable from MuMTV RNA recovered from lactating mammary glands of BALB/c females carrying only endogenous MuMTV proviruses, suggesting that endogenous MuMTV RNA sequences were induced in hormone-induced neoplasms. RNA indistinguishable from MuMTV sequences present in hormone-induced primary tumors was also detected in multiple genomic equivalents in two independently derived hormone-induced premalignant alveolar hyperplasias. MuMTV p28 was detected, but gp52 was not. The same hormone stimulus that generated 100% tumors in normal glands greatly accelerated tumor development in premalignant hyperplasias but did not amplify MuMTV RNA or antigens in either hyperplasias or the tumors derived from them. B-type virions were not detected in these tissues, in either hypophyseal implant-stimulated or virgin hosts. Cell-free virions were not detected in culture. These data suggest that the replication of MuMTV induced in hormone-induced neoplasms is defective. Details of its expression suggest that if involved in events leading to tumors, its involvement is insufficient cause for those tumors.