tbuckley/cabot-search huggingface dataset:
Phase I study of liposomal MTP-PE-activated autologous monocytes administered intraperitoneally to patients with peritoneal carcinomatosis.
Authors: A Faradji, A Bohbot, H Frost, M Schmitt-Goguel, J C Siffert, P Dufour, M Eber, C Lallot, M L Wiesel, J P Bergerat
Journal: Journal of Clinical Oncology (1991)

We have conducted a phase I study with autologous monocytes activated ex vivo and administered intraperitoneally in nine patients with peritoneal carcinomatosis. Blood monocytes were collected by leukapheresis and then purified by counterflow elutriation (up to 10(9) cells, with a purity of greater than 90%). Ex vivo activation was obtained by incubating these cells with 1 micrograms liposomal MTP-PE/10(6) monocytes for 18 hours in hydrophobic culture bags at 37 degrees C in 5% carbon dioxide humidified air. The activated monocytes were then infused in the peritoneal cavity once a week for 5 consecutive weeks through an implanted peritoneal infusion system, Port-A-Cath (Pharmacia Deltec, St Paul, MN), on an intrapatient dose-escalating schedule (10(7) to 10(9) monocytes). No severe adverse reactions occurred. Toxicity was mild, the chief acute reactions being fever (27%), chills (13%), and abdominal pain (25%). None of the side effects led to dose reduction. No consistent change in hemostatic function, liver function, or renal function was observed. Significant increases in granulocyte counts, neopterine, and acute phase reactants (fibrinogen, C-reactive protein) occurred in the peripheral blood. In vitro monocyte activation was demonstrated by the relapse of procoagulant activity and monokines (interleukin-1 [IL-1], IL-6, and tumor necrosis factor-alpha [TNF alpha]) in the supernatants of cultured monocytes. Evidence for in vivo monocyte activation was provided by the increase of these monokines in the peritoneal fluids. Kinetic studies with indium-111 (111In)-labeled activated autologous monocytes in five patients suggest that these infused monocytes may remain in the peritoneal cavity for up to 7 days. This locoregional immunotherapeutic approach seems to be encouraging in view of adjuvant therapeutic modality in ovarian cancer patients with minimal residual intraabdominal disease following second-look laparotomy.
Evaluation of the Plain Abdominal X-ray in the Acute Abdomen
Authors: M J Stower, T Mikulin, J D Hardcastle, S S Amar, D M Kean
Journal: Journal of the Royal Society of Medicine (1985)

The prognostic value of an erect and supine abdominal X-ray was studied prospectively in 97 patients with an acute abdomen. Although 64 (66%) of the radiographs showed an abnormality, the surgical registrar altered his clinical diagnosis on only seven occasions and changed his management on four. A consultant radiologist was the most accurate at reporting the X-rays even without seeing the patient, whilst junior surgical and radiological staff were as accurate as each other. A surgical registrar, however, was more accurate than junior radiologists in making a diagnosis. The investigation was of immediate clinical value in only 4% of the patients, and its use could probably be limited without detriment to patients.
Single center experience with systematic diagnostic and predictive genetic screening for pulmonary arterial hypertension
Authors: Rozenn Quarck, Thomy De Ravel, Catharina Belge, Wim Wuyts, Bjorn Cools, Marion Delcroix
Journal: European Respiratory Journal (2014)

Germline mutations in the gene encoding for bone morphogenic receptor-2 (BMPR2) can cause pulmonary arterial hypertension (PAH). Molecular genetic diagnosis and counseling is currently available but not broadly implemented due to poor translation in direct clinical benefit.  We aim to investigate the influence of BMPR2 mutation on clinical outcome in PAH and selected parameters of long-term transthoracic echocardiography (TTE) and cardiopulmonary exercise test (CPET) follow-up in heritable PAH (HPAH) patient relatives.  BMPR2 mutation screening was performed in 124 sporadic or familial idiopathic PAH patients. Clinical, functional, hemodynamic parameters and outcome were compared in 23 BMPR2 mutation carriers and 101 noncarriers. Predictive screening was carried out in 53 HPAH relatives. TTE and CPET were performed repeatedly in 18 carriers and 15 noncarriers HPAH patient relatives, respectively.  As compared with noncarriers, BMPR2 mutation carriers were younger at diagnosis, had higher mean pulmonary artery, and pulmonary vascular resistance but similar time to clinical worsening and overall survival. Baseline TTE and CPET parameters were similar in HPAH relatives carrying or not BMPR2 mutation, and remained unchanged along an average 6-year follow-up in HPAH relatives carrying BMPR2 mutation, except for 2 patients who developed severe symptomatic PAH between 1 st  and 2 nd  follow-up.  Our data confirm that BMPR2 mutation carriers with PAH are diagnosed earlier than noncarriers, with more severe hemodynamic and functional profile. In addition, HPAH relatives carrying BMPR2 mutation do not display early TTE or CPET impairments allowing predicting the development of PAH.
Bilateral Oxford Meniscal Knee Arthroplasty
Authors: K P Sherman, S Tibrewal, J Goodfellow, J O'Connor
Journal: Journal of the Royal Society of Medicine (1985)

Thirty-two patients who underwent bilateral bicompartmental Oxford Meniscal Knee arthroplasty have been followed up prospectively for a mean period of 51 months from the time of their first operation. Pain relief was obtained in all but one knee; walking ability was improved in more than two-thirds. Overall patient satisfaction with the results was good. Two knees failed. The results demonstrate that bilateral knee arthroplasty can be expected to give good functional results.
Gene expression profile testing for breast cancer: Patterns and predictors of use and impact on chemotherapy.
Authors: M. J. Hassett, J. C. Niland, M. E. Hughes, R. L. Theriault, D. W. Blayney, Y. Wong, C. Hudis, P. K. Marcom, C. Laronga, J. C. Weeks
Journal: Journal of Clinical Oncology (2010)

566 Background: A test that analyzes the expression profile of 21 genes has offered women with hormone receptor positive breast cancer (HR+BC) useful prognostic and predictive information since it became available in 2004. Unfortunately, we know little about how this test is used in general practice or what impact it has had on quality of care. Methods: To better understand when and for whom the recurrence score test is obtained and what impact it has had on chemotherapy, we identified adult women diagnosed 2006-8 with stage I-III HR+BC and treated at one of 11 institutions participating in the National Comprehensive Cancer Network's prospective outcomes database. We characterized the frequency of testing, identified predictors of testing using multivariable logistic regression and described trends in chemotherapy use. Results: Of 6,642 women, 22% had a recurrence score. Testing varied by institution (12% to 37%; p < 0.01), and increased from 2006 to 2008 among N- (23% to 38%; p < 0.01) and N+ (1% to 10%; p < 0.01) cancers. Results for 1,379 tests (97%) were available: 52% low, 36% intermediate and 9% high risk. Predictors of testing included age 50-59 vs. < 50 (OR 1.2), education beyond high school vs. high school or less (OR 1.6), and HER2- vs. HER2+ (OR 6.0). Factors associated with lower odds of testing included African-American vs. Caucasian non-Hispanic (OR 0.7), unemployed vs. employed/student (OR 0.7), age ≥ 70 vs. < 50 (OR 0.3), ER-/PR+ vs. ER+/PR+ (OR 0.2) and high vs. other grade (OR 0.7). Compared with 1-2 cm tumors, the odds of testing < 1, 2.1-3 and > 3 cm tumors were lower (0.3, 0.6 and 0.3). [p < 0.05 for all predictors] Chemotherapy was administered to 14% of low risk, 47% of intermediate risk, 84% of high risk and 57% of untested cancers; chemotherapy use decreased from 54% in 2006 to 46% in 2008. Conclusions: Recurrence scores were used in cancers without high risk features to identify when to forego chemotherapy; testing increased and chemotherapy use decreased over time. Socio-demographic disparities in testing were identified. Potential quality of care issues that warrant further investigation include test over use among cancers unlikely to be high risk, chemotherapy under use among high risk cancers and chemotherapy over use among low risk cancers. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genomic Health BlueCross BlueShield of Michigan
Diagnosis of Tuberculous Meningitis
Authors: P Monteyne, C J Sindic
Journal: BMJ (1961)

The incidence of tuberculosis (TB) is expected to increase substantially during the next 10 years as well as its extrapulmonary manifestations, often in association with the HIV panepidemic. TB meningitis displays some clinical and radiological characteristics but the "gold standard" for diagnosis remains the identification of Mycobacterium tuberculosis in the CSF by direct staining of culture. Direct staining, however, is rarely successful and culturing of M. Tuberculosis can take 4 to 8 weeks. Other techniques may be helpful, such as the detection of an intrathecal synthesis of antimycobacterial antibodies, or the detection in the CSF of the mycobacterial genome by the polymerase chain reaction (PCR). DNA amplification, and especially the "nested" amplification protocol, may represent a major step forward and find its place as a sensitive, specific and rapid test in the routine diagnostic laboratory.
Biomarkers for sputum eosinophilia in mild-moderate and severe adult-onset asthma patients
Authors: Guus Westerhof, Daniel Korevaar, Marijke Amelink, Selma De Nijs, Christa de Groot, Els Weersink, Anneke ten Brinke, Patrick Bossuyt, Elisabeth Bel
Journal: European Respiratory Journal (2014)

Introduction Eosinophilic airway inflammation is an important pathological characteristic of severe asthma. Treatment guided by sputum eosinophils reduces asthma exacerbations, but differential sputum cell counts are not widely available.

Aim We aimed to estimate the diagnostic accuracy of non-invasive biomarkers for sputum eosinophilia in adult-onset asthma patients.

Methods Three observational clinical trials enrolled patients with adult-onset asthma from pulmonary outpatient clinics. Blood and sputum eosinophils, exhaled nitric oxide (FeNO) and total IgE were assessed in 1-2 days, in 336 patients. In retrospective analyses, area under the receiver operating characteristics curve (AUC) was used to express the accuracy of blood eosinophils, FeNO and IgE in detecting sputum eosinophilia (threshold ≥3%).

Results Sputum eosinophilia was present in 116 patients (35 %). The AUC for blood eosinophils was 0.83 (95%CI 0.78-0.87), vs 0.82 for FENO (95%CI 0.77-0.87) and 0.69 (95%CI 0.63-0.75) for total IgE. AUC's in patients with mild-moderate asthma and severe asthma were, respectively, 0.82 and 0.81 (p=.92) for FeNO, 0.78 and 0.87 (p=.08) for blood eosinophils and 0.66 and 0.68 (p=.67) for IgE.

![Figure][1] 



Conclusion Both blood eosinophils and FeNO have reasonable accuracy as markers of airway eosinophilia in adult-onset asthma patients; there is no difference in accuracy between mild-moderate and severe asthma patients.

 [1]: pending:yes
Noninvasive ventilation in severe life threatening asthma
Authors: Yahya Abazed, Kerstin Krause, Gerhard Laier-Groeneveld, Husam Musleh
Journal: European Respiratory Journal (2014)

Patients with life threatening asthma suffer from episodic or long lasting overload of the respiratory muscles. In case of failure they require mechanical Ventilation (MV). If noninvasive ventilation is helpful in such disease is under debate.  Methods: We report on two patients, who present severe airway obstructions and frequent life threatening asthma attacks. They were adapted to MV to use it daily and during their attacks. MV was set to completely unload the respiratory muscles to a degree that respiratory efforts were not necessary even during severe asthma attacks. They were trained over several weeks.  Both patients had previously undergone multiple attempts to improve their asthma (high dose steroids, Xolair, Interferon, etc.) and been intubated several times. Daily corticoid dose ranged from 300 to 500mg (patient 1) and above 100mg (patient 2) together with high dose of s agonists and inhaled corticosteroids.  Results: To achieve a complete unloading during different levels of obstructions the volume preset mode was used with a tidal volume of 1.3l, PEEP=0, respiratory rate 20 and inspiration time of 1.2s resulting in a ventilation pressure exceeding 60mbar. Both patient´s diaries showed daily attacks and 3 to 6 life threatening events per month during which they effectively used MV. All attacks were managed at home and hospital stay decreased to 1 per year. The patients explain their experience and how to use MV in such critical situations.  Conclusion: Passive noninvasive ventilation with high tidal volume and rapid inspiratory flow can unload the respiratory muscles even during most severe asthma attacks to avoid invasive ventilation. Intensive training to adapt to such ventilation is necessary.
Prognostic Value of Histologic Grade and Proliferative Activity in Axillary Node–Positive Breast Cancer: Results From the Eastern Cooperative Oncology Group Companion Study, EST 4189
Authors: Jean F. Simpson, Robert Gray, Lynn G. Dressler, Charles D. Cobau, Carla I. Falkson, Kennedy W. Gilchrist, Kishan J. Pandya, David L. Page, Nicholas J. Robert
Journal: Journal of Clinical Oncology (2000)

PURPOSE: The identification of a subset of patients with axillary lymph node–positive breast cancer with an improved prognosis would be clinically useful. We report the prognostic importance of histologic grading and proliferative activity in a cohort of patients with axillary lymph node–positive breast cancer and compare these parameters with other established prognostic factors. PATIENTS AND METHODS: This Eastern Cooperative Oncology Group laboratory companion study (E4189) centered on 560 axillary lymph node–positive patients registered onto one of six eligible clinical protocols. Flow cytometric (ploidy and S-phase fraction [SPF]) and histopathologic analyses (Nottingham Combined Histologic Grade and mitotic index) were performed on paraffin-embedded tissue from 368 patients. RESULTS: Disease recurred in 208 patients; in 161 (77%), within the first 5 years. Mitotic index and grade were associated with both ploidy and SPF (P ≤ .01). Within the first 5 years of follow-up, mitotic index (P = .004), grade (P = .004), ploidy (P = .006), and SPF (P = .05) were associated with time to recurrence; there was also a significant association with survival. The effect of mitotic index was largely a result of the difference between 0 to 2 mitoses/10 high-power fields (HPF; 5-year recurrence of 31%) and more than 2 mitoses/10 HPF (5-year recurrence of 52%). The 0 to 2 mitoses/10 HPF group was independently associated with improved prognosis at 5 years (P = .002) in regression models that included other standard prognostic factors. CONCLUSION: A subset of axillary lymph node–positive patients with improved prognosis may be identified using a lower (&lt; 3 mitoses/10 HPF) mitotic count than is usually performed.
Training in oral medicine
Authors: Joanna M Zakrzewska
Journal: Journal of the Royal Society of Medicine (2001)

88 members of the UK specialty society of oral medicine were asked about career satisfaction and their views on training programmes. 70% responded (79% of consultants and all accredited trainees). Men work longer hours than women, report less control over their work and experience more stress. Although high work satisfaction is reported, nearly one-third regret their choice of specialty. Men more than women do locum work while training. Most respondents would welcome flexible training, job shares, financial support during training and a mentoring scheme.
Use of household cleaning products, exhaled nitric oxide and lung function in females
Authors: Nicole Le Moual, Marta Rava, Valérie Siroux, Régis Matran, Rachel Nadif
Journal: European Respiratory Journal (2014)

To the Editor: 

We read with great interest, a report by Casas et al. [1], in a recent issue of the European Respiratory Journal, who studied the relationship between domestic use of cleaning products, reported by the mother, and exhaled nitric oxide fraction ( F eNO) and lung function in children. They concluded that passive exposure to cleaning products may increase airway inflammation in children and may have an adverse effect on lung function [1]. Cleaning products contain numerous chemicals such as irritants (bleach and ammonia) or sensitisers (perfumes) and may cause asthma [2]. The mechanisms are partly unknown [1–3], but could be related to chronic inflammatory changes [4, 5]. The results presented by Casas et al. [1] are of great importance and are consistent with the hypothesis of an inflammatory role of cleaning agents.

We similarly tested the hypothesis of an inflammatory effect of domestic use of cleaning products among adults, by studying their relationships with F eNO among 313 females (197 without asthma and 116 with current asthma; mean age 42 years; 53% never-smokers) from the Epidemiological Study on the Genetics and Environment of Asthma (EGEA) [3, 6]. Both domestic exposures and phenotypes were evaluated by similar methods to those reported by Casas et al. [1]. Briefly, EGEA is a French cohort study based on an initial group of asthma cases, their first-degree relatives, and controls (1991–1995). A follow-up of the cohort was conducted between 2003 and 2007, and detailed information was recorded by questionnaires and health examinations such as pulmonary lung function tests [3, 6]. F eNO measurements, available in three out of five centres (performed for 313 out of 683 females), …
Outside In: Sequencing the Lung Microbiome
Authors: Michael J. Cox, Miriam F. Moffatt, William O. C. Cookson
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Molecular techniques have revolutionised the practise of standard microbiology.In particular, 16S rRNA sequencing, whole microbial genome sequencing and metagenomics are revealing the extraordinary diversity of microorganisms on Earth and their vast genetic and metabolic repertoire.The increase in length, accuracy and number of reads generated by high-throughput sequencing has coincided with a surge in interest in the human microbiota, the totality of bacteria associated with the human body, in both health and disease.Traditional views of host/pathogen interactions are being challenged as the human microbiota are being revealed to be important in normal immune system function, to diseases not previously thought to have a microbial component and to infectious diseases with unknown aetiology.In this review, we introduce the nature of the human microbiota and application of these three key sequencing techniques for its study, highlighting both advances and challenges in the field.We go on to discuss how further adoption of additional techniques, also originally developed in environmental microbiology, will allow the establishment of disease causality against a background of numerous, complex and interacting microorganisms within the human host.
Abstract 1941: GSK3 signaling is critical to glioma stem cell growth and survival
Authors: Angel Alvarez, Andrey Ugolkov, Irina Gaisina, Alan P. Kozikowski, Kaushal Joshi, Sunghak Kim, Ichiro Nakano, Jeffrey J. Raizer, Andrew P. Mazar, Bo Hu, Shi-Yuan Cheng
Journal: Cancer Research (2014)

Abstract GSK3 is an attractive therapeutic target in cancer, known for its role in regulating proliferation, differentiation, metabolism, and apoptosis. Previous studies demonstrate the effectiveness of GSK3 inhibition on established glioma cell lines and patient-derived glioma stem cell lines in vitro and in vivo. In glioma cell lines, GSK3 inhibition induces apoptosis through c-MYC activation, mitochondrial destabilization, and reduction of NF-κB activity. We have characterized a novel set of GSK3 inhibitors for their ability to inhibit glycogen synthase phosphorylation, reduce levels of XIAP, and induce cell death in cancer cells. However, it is uncertain if this mechanism is functional with respect to cancer stem cells and glioma tumor subtype. The need to investigate the mechanistic effects of GSK3 in cancer stem cells is important given their malignancy, innate resistance to therapy, and tumorigenicity. Moreover, the intracellular signaling and transcription networks may differ in glioma stem cells, particularly among cells with different subtypes. We have recently demonstrated that cancer stem cells isolated from glioma patients can be segregated into either a proneural or mesenchymal subtype based on their gene expression pattern. The oncogenic activity of genes like c-MYC in glioma stem cells and differences between glioma stem cell subtypes, such as NF-κB activation, raises questions as to whether GSK3 inhibition will be effective against both subtypes and if their effects utilize distinct mechanisms of inhibition. In this study, we examine the effects of two established and two novel GSK3 inhibitors on glioma stem cells with respect to tumor subtype and investigate their mechanisms of action. Our in vitro data shows that GSK3 inhibition significantly reduces growth and causes cell death in both proneural and mesenchymal glioma stem cells. Using a glioma stem cell xenograft model, we test the effectiveness of GSK3 inhibition as a single agent and in conjunction with clinically-approved chemotherapeutic agents. The characterization of cancer stem cell inhibitors and their effectiveness in different tumor subtypes has significant clinical implications. Our work supports the therapeutic potential of novel GSK3 inhibitors for the treatment of malignant gliomas. Note: This abstract was not presented at the meeting. Citation Format: Angel Alvarez, Andrey Ugolkov, Irina Gaisina, Alan P. Kozikowski, Kaushal Joshi, Sunghak Kim, Ichiro Nakano, Jeffrey J. Raizer, Andrew P. Mazar, Bo Hu, Shi-Yuan Cheng. GSK3 signaling is critical to glioma stem cell growth and survival. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1941. doi:10.1158/1538-7445.AM2014-1941
Preliminary Results From the Cancer Research Campaign Trial Evaluating Tamoxifen Duration in Women Aged Fifty Years or Older With Breast Cancer
Journal: JNCI Journal of the National Cancer Institute (1996)

Background Although trials of postsurgical tamoxifen therapy for patients with breast cancer have convincingly demonstrated reductions in relapse rates and improvements in survival, the optimal duration of therapy is as yet unclear. Purpose : Our objective is to determine whether 2 or 5 years of tamoxifen therapy (20mg/day orally) is preferable in the treatment of patients with early breast cancer.