tbuckley/cabot-search huggingface dataset:
Simulation-Based Trial of Surgical-Crisis Checklists
Authors: Alexander F. Arriaga, Angela M. Bader, Judith M. Wong, Stuart R. Lipsitz, William R. Berry, John E. Ziewacz, David L. Hepner, Daniel J. Boorman, Charles N. Pozner, Douglas S. Smink, Atul A. Gawande
Journal: New England Journal of Medicine (2013)

Operating-room crises (e.g., cardiac arrest and massive hemorrhage) are common events in large hospitals but can be rare for individual clinicians. Successful management is difficult and complex. We sought to evaluate a tool to improve adherence to evidence-based best practices during such events.Operating-room teams from three institutions (one academic medical center and two community hospitals) participated in a series of surgical-crisis scenarios in a simulated operating room. Each team was randomly assigned to manage half the scenarios with a set of crisis checklists and the remaining scenarios from memory alone. The primary outcome measure was failure to adhere to critical processes of care. Participants were also surveyed regarding their perceptions of the usefulness and clinical relevance of the checklists.A total of 17 operating-room teams participated in 106 simulated surgical-crisis scenarios. Failure to adhere to lifesaving processes of care was less common during simulations when checklists were available (6% of steps missed when checklists were available vs. 23% when they were unavailable, P<0.001). The results were similar in a multivariate model that accounted for clustering within teams, with adjustment for institution, scenario, and learning and fatigue effects (adjusted relative risk, 0.28; 95% confidence interval, 0.18 to 0.42; P<0.001). Every team performed better when the crisis checklists were available than when they were not. A total of 97% of the participants reported that if one of these crises occurred while they were undergoing an operation, they would want the checklist used.In a high-fidelity simulation study, checklist use was associated with significant improvement in the management of operating-room crises. These findings suggest that checklists for use during operating-room crises have the potential to improve surgical care. (Funded by the Agency for Healthcare Research and Quality.).
Significance of Sentinel Lymph Node Micrometastases in Patients With Breast Cancer
Authors: David E. Gyorki, Michael A. Henderson
Journal: Journal of Clinical Oncology (2010)

TO THE EDITOR: Hansen et al report an interesting analysis of the significance of micrometastatic sentinel lymph node (SLN) involvement in breast cancer. They conclude that patients with isolated tumor cells (ITCs) and micrometastatic tumor deposits measuring smaller than 2 mm (American Joint Committee on Cancer nodal stage pN0[i ] and pN1mi) do not have worse 8-year disease-free survival or overall survival compared with SLN-negative patients (pN0). However, they do demonstrate significantly reduced survival for patients with SLN metastases larger than 2 mm (pN1). This is in contrast with a large recently published retrospective review from the Netherlands, which demonstrated reduced 5-year disease-free survival in patients with both ITCs and micrometastatic disease in the SLN. We are concerned by Hansen et al’s failure to include details of the primary tumor characteristics (ie, tumor grade and receptor status) in their report. Table 3 reveals that only 54% of SLN-negative patients received adjuvant hormone therapy (tamoxifen group and chemotherapy and tamoxifen group) compared with 76.1%, 72.2%, and 66.9% for the groups with ITCs, micrometastases, and macrometastases, respectively. Is this because the SLN-negative patients were not routinely administered adjuvant hormone therapy or because estrogen receptor–negative patients are over-represented in this group? If the latter is true, the SLN-negative group would be expected to have a worse prognosis. In the multivariate analysis, SLN status was categorized as macrometastatic or all others. Patients with ITCs and micrometastases represented only 22.2% of this group. The majority of patients in this comparative group were SLN negative (pN0). It is not surprising that a difference was found when they were compared with the macrometastatic group. The number of patients in the ITC and micrometastatic groups who developed a failure event (ie, disease recurrence or death) is rather small (Fig 3 of Hansen et al), and the CIs for disease-free and overall survival for these groups are likely to be large. Therefore, it is not possible to convincingly argue that patients with ITCs and micrometastatic tumor deposits do not have worse prognosis than patients with macrometastatic disease in the SLN. The significance of finding ITCs or micrometastatic disease burden in the SLN of patients with breast cancer remains a considerable management dilemma. SLN status is an important determinant for adjuvant therapy decision making, and additional studies are required to better understand the biologic significance of low-volume disease in the SLN.
Relation between dose of bendrofluazide, antihypertensive effect, and adverse biochemical effects.
Authors: J E Carlsen, L Kober, C Torp-Pedersen, P Johansen
Journal: BMJ (1990)

OBJECTIVE--To determine the relevant dose of bendrofluazide for treating mild to moderate hypertension. DESIGN--Double blind parallel group trial of patients who were given placebo for six weeks and then randomly allocated to various doses of bendrofluazide (1.25, 2.5, 5, or 10 mg daily) or placebo for 12 weeks. SETTING--General practices in Zealand, Denmark. PATIENTS--257 Patients with newly diagnosed or previously treated hypertension, aged 25-70, who had a mean diastolic blood pressure of 100-120 mm Hg after receiving placebo for six weeks. MAIN OUTCOME MEASURES--Reduction in diastolic blood pressure and changes in biochemical variables (potassium, urate, glucose, fructosamine, total cholesterol, apolipoprotein A I, apolipoprotein B, and triglyceride concentrations). RESULTS--All doses of bendrofluazide significantly reduced diastolic blood pressure to the same degree (10-11 mm Hg). Clear relations between dose and effect were shown for potassium, urate, glucose, total cholesterol, and apolipoprotein B concentrations. The 1.25 mg dose increased only urate concentrations, whereas the 10 mg dose affected all the above biochemical variables. CONCLUSION--The relevant range of doses of bendrofluazide to treat mild to moderate hypertension is 1.25-2.5 mg a day. Higher doses caused more pronounced adverse biochemical effects including adverse lipid effects. Previous trials with bendrofluazide have used too high doses.
Activation of the p21ras pathway couples antigen receptor stimulation to induction of the primary response gene egr-1 in B lymphocytes.
Authors: S B McMahon, J G Monroe
Journal: The Journal of Experimental Medicine (1995)

The primary response gene egr-1 encodes a sequence-specific transcription factor whose expression is necessary for antigen receptor-stimulated activation of B lymphocytes. The molecular processes involved in linking egr-1 induction to antigen receptor signaling have not been defined. The present study demonstrates that expression of an activated form of p21ras results in egr-1 induction similar to that previously shown after antigen receptor cross-linking. In addition, both antigen receptor cross-linking and p21ras use the same element in the egr-1 promoter to exert their effects. Using dominant-negative mutants of p21ras and raf-1, we demonstrate that induction of egr-1 after antigen receptor cross-linking is mediated by activation of the p21ras/mitogen-activated protein kinase signaling pathway. While regulation of the p21ras pathway during B cell activation has been intensively studied, this report represents the first description of a biologically relevant event associated with its activation.
Restriction of HIV-1 replication in macrophages and CD4+ T cells from HIV controllers
Authors: Asier Sáez-Cirión, Chiraz Hamimi, Anna Bergamaschi, Annie David, Pierre Versmisse, Adeline Mélard, Faroudy Boufassa, Françoise Barré-Sinoussi, Olivier Lambotte, Christine Rouzioux, Gianfranco Pancino
Journal: Blood (2011)
Evaluation of treatment with fixed dose combinations in asthma patients in primary care in Sweden by using mannitol challenge test
Authors: Kerstin Romberg, Anna-Carin Berggren
Journal: European Respiratory Journal (2012)

Background: The mannitol challenge test is an indirect bronchial challenge test suitable for use in a primary-care setting. The test is most often used to diagnose asthma. In this pilot study the test was used to evaluate the effectiveness of ongoing treatment with ICS/LABA combination therapy in patients with asthma.

Objectives: To explore the prevalence of optimal treated asthma patients in primary care in Sweden. The hypothesis was that not all patients are optimal treated.

Methods: Male and female subjects, age 18-65 years with asthma, who were treated with a fixed dose combination (budesonide/formoterol or fluticasone/salmeterol) were included in the study. The subjects performed a mannitol challenge test (direct fall) followed by an inhalation of a β2-agonist. A new spirometry (reversibility test) was performed 15 minutes later. The main explorative end-point was positive or negative response of mannitol challenge test and/or a reversibility of ≥15%.

Results: The preliminary result of this pilot study (100 subjects) shows that an unexpected, surprisingly high proportion of the asthma patients had a positive response, either as a direct fall of FEV1 ≥15% in the mannitol challenge test and/or a reversibility of ≥15%.

Conclusion: The result of this study indicates that a large proportion of asthma patients in primary care, who are currently treated with fixed dose combination therapy, may not be optimally treated. Further research is needed to support these findings and to understand the reasons.
Preferential association of a functional variant in complement receptor 2 with antibodies to double-stranded DNA
Authors: Jian Zhao, Brendan M Giles, Rhonda L Taylor, Gabriel A Yette, Kara M Lough, Han Leng Ng, Lawrence J Abraham, Hui Wu, Jennifer A Kelly, Stuart B Glenn, Adam J Adler, Adrienne H Williams, Mary E Comeau, Julie T Ziegler, Miranda Marion, Marta E Alarcón-Riquelme, Graciela S Alarcón, Juan-Manuel Anaya, Sang-Cheol Bae, Dam Kim, Hye-Soon Lee, Lindsey A Criswell, Barry I Freedman, Gary S Gilkeson, Joel M Guthridge, Chaim O Jacob, Judith A James, Diane L Kamen, Joan T Merrill, Kathy Moser Sivils, Timothy B Niewold, Michelle A Petri, Rosalind Ramsey-Goldman, John D Reveille, R Hal Scofield, Anne M Stevens, Luis M Vilá, Timothy J Vyse, Kenneth M Kaufman, John B Harley, Carl D Langefeld, Patrick M Gaffney, Elizabeth E Brown, Jeffrey C Edberg, Robert P Kimberly, Daniela Ulgiati, Betty P Tsao, Susan A Boackle
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> Systemic lupus erythematosus (SLE; OMIM 152700) is characterised by the production of antibodies to nuclear antigens. We previously identified variants in complement receptor 2 (<i>CR2/CD21</i>) that were associated with decreased risk of SLE. This study aimed to identify the causal variant for this association. <h3>Methods</h3> Genotyped and imputed genetic variants spanning <i>CR2</i> were assessed for association with SLE in 15 750 case-control subjects from four ancestral groups. Allele-specific functional effects of associated variants were determined using quantitative real-time PCR, quantitative flow cytometry, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)-PCR. <h3>Results</h3> The strongest association signal was detected at rs1876453 in intron 1 of <i>CR2</i> (p<sub>meta</sub>=4.2×10<sup>−4</sup>, OR 0.85), specifically when subjects were stratified based on the presence of dsDNA autoantibodies (case-control p<sub>meta</sub>=7.6×10<sup>−7</sup>, OR 0.71; case-only p<sub>meta</sub>=1.9×10<sup>−4</sup>, OR 0.75). Although allele-specific effects on B cell <i>CR2</i> mRNA or protein levels were not identified, levels of complement receptor 1 (<i>CR1/CD35)</i> mRNA and protein were significantly higher on B cells of subjects harbouring the minor allele (p=0.0248 and p=0.0006, respectively). The minor allele altered the formation of several DNA protein complexes by EMSA, including one containing CCCTC-binding factor (CTCF), an effect that was confirmed by ChIP-PCR. <h3>Conclusions</h3> These data suggest that rs1876453 in <i>CR2</i> has long-range effects on gene regulation that decrease susceptibility to lupus. Since the minor allele at rs1876453 is preferentially associated with reduced risk of the highly specific dsDNA autoantibodies that are present in preclinical, active and severe lupus, understanding its mechanisms will have important therapeutic implications.
Value of fibreoptic bronchoscopy in the diagnosis of complicated pulmonary unilocular cystic hydatidosis
Authors: A Saygi, I Oztek, M Guder, F Sungun, B Arman
Journal: European Respiratory Journal (1997)

Complicated pulmonary unilocular cystic hydatidosis (CPUCH) is a serious condition, which requires immediate treatment. The aim of the present study was to evaluate the efficacy of fibreoptic bronchoscopy (FOB) in the final diagnosis of CPUCH. Of 1,726 cases, who underwent FOB evaluation between 1990 and 1994 in our centre, 24 patients (17 females and 7 males), who had proven CPUCH after thoracotomy, were included in this study. Fourteen of the 24 cases were diagnosed in the preoperative period by cytological and histopathological evaluation of FOB material, whereas the remaining 10 cases with presumed CPUCH underwent thoracotomy for final diagnosis. Of the 14 cases diagnosed by FOB (11 females and 3 males); none had concomitant extrapulmonary hydatid disease. Whitish-yellow membranes were seen in 12 of the cases during FOB. Whilst cuticular particles, degenerated scoleces, and hooklets were seen in 14 cases in bronchial lavage, these elements were identified in brushing material in only seven. In 10 of the 14 cases, cytological diagnosis was confirmed by FOB biopsies before thoracotomy. It is concluded that whilst the clinical, radiological and laboratory findings are presumptive, fibreoptic bronchoscopic examination and the cytological and histopathological examination of material obtained during that procedure are conclusive for the diagnosis of complicated pulmonary unilocular cystic hydatidosis.
Evidence for a dual effect by beta-adrenoceptor antagonists on post-exercise airway calibre
Authors: KE Berkin, G Walker, NC Thomson
Journal: European Respiratory Journal (1988)

The effect of selectivity of beta-adrenoceptor antagonists on resting and post-exercise airway calibre in normal subjects was studied. Eight normal subjects were given atenolol 50 mg, propranolol 80 mg and placebo orally, in random order, double-blind. Specific airways conductance and flow-volume curves (partial and complete) were recorded before, 2 hours after drug administration and after exercise. Neither beta-adrenoceptor antagonist had a measurable effect on lung function tests at rest. The post-exercise increase in flow rates measured from partial flow volume curves was inhibited by propranolol but not by the beta-1-selective adrenoceptor antagonist atenolol, whereas both drugs caused a decrease in specific airways conductance after exercise. Beta-adrenoceptor antagonists may have a dual effect on airway calibre. Firstly, a direct effect on the beta-2 receptors in airway smooth muscle may occur. Secondly, beta-adrenoceptor blockade may, in the large airways, inhibit vagal pre-junctional beta-1 receptors which normally inhibit acetylcholine release at the nerve ending, thereby permitting vagally-induced airway narrowing.
Concurrent radiation therapy and chemotherapy for locally unresectable squamous cell head and neck cancer: an Eastern Cooperative Oncology Group pilot study.
Authors: D J Adelstein, L A Kalish, G L Adams, H Wagner, M M Oken, S C Remick, E G Mansour, R E Haselow
Journal: Journal of Clinical Oncology (1993)

The feasibility and success of an intensive chemoradiotherapeutic protocol for patients with locally advanced, unresectable squamous cell head and neck cancer was tested in this limited-institution, Eastern Cooperative Oncology Group phase II pilot study.Between December 1987 and September 1989, 57 patients were entered onto this trial. The treatment protocol consisted of three courses of a 4-day continuous fluorouracil infusion, a single cisplatin bolus injection, and concurrent split-course radiotherapy. After 30 Gy of radiation and two chemotherapy courses, patients were evaluated for response and for the possibility of surgical resection.Fifty-five of 57 registered patients are assessable for toxicity and 52 are assessable for response and survival. Toxicity was significant, but tolerable, although there were three toxic deaths. A complete response to this treatment was ultimately achieved by 77% of patients. Twenty-four patients remain relapse-free. The projected Kaplan-Meier 4-year relapse-free survival rate is 45% and the overall survival rate is 49%. Median relapse-free and overall survival durations are 26 and 37 months, respectively. Of the 28 treatment failures, 79% were locoregional. Fourteen patients underwent surgery. Six remain relapse-free.This aggressive concurrent chemoradiotherapy protocol appears feasible within a cooperative group. Treatment results are promising and appear durable. A randomized phase III clinical trial is currently underway.
P12.01 * SURGERY WITH INTRA-OPERATIVE NEUROPHYSIOLOGICAL MONITORING IN THE MANAGEMENT OF THALAMIC ASTROCYTOMAS
Authors: G. Carrabba, G. Bertani, G. Ardolino, F. Cogiamanian, B. Zarino, M. Locatelli, S. Barbieri, M. Caroli, P. Rampini
Journal: Neuro-Oncology (2014)

INTRODUCTION: The thalamus is a deep-seated and crucial structure for the sensory-motor system. It has been longly considered a surgically inaccessible area due to the morbidity associated with surgical resections. In fact, astrocytomas of the thalamus usually undergo bioptic procedures followed by adjuvant treatments (if indicated). Intra-operative neurophysiological monitoring (IONM) allows safe and satisfactory resections of lobar gliomas. Considering the need of reliable specimens for the pathological diagnosis and that the extent of resection is positively associated with overall survival, aim of this study was to review the feasibility and outcome of a small series of patients with thalamic astrocytomas operated with the aid of IONM. PATIENTS AND METHODS: Five patients with thalamic astrocytomas (1 grade I, 3 grade III, 1 grade IV) underwent surgical resection with IONM. Two astrocytomas were in the dominant hemisphere. All patients performed pre-operative and post-operative neuropsychological assessment. IONM consisted in transcranial MEP monitoring (4 patients), cortical MEP monitoring (2 patients), direct electrical stimulation (5 patients), EEG (5 patients) and ECoG monitoring (2 patients). Anesthesia was totally intra-venous (propofol + remifentanyl) for all patients; 1 patients was operated following an asleep-awake protocol, 4 following an asleep-asleep protocol. RESULTS: None of patients suffered from permanent motor deficits; 2 patients had a transient hemiparesis requiring rehabilitation; 1 patient suffered a transient aphasia, and 1 patient had permanent aphasia. None of the patients had intraoperative seizures, but 1 patient had a post-operative transient status epilepticus. Resection was total or subtotal in 3 cases and partial (with resection between 50 and 80% of the tumor volume) in the other 2 cases. CONCLUSIONS: Surgical resection of thalamic astrocytomas could be meaningful and relatively safe when guided by IONM. Larger series of patients are required to confirm this preliminary data.
Are Fluorescent Organic Nanoparticles Relevant Tools for Tracking Cancer Cells or Macrophages?
Authors: Adrien Faucon, Houda Benhelli‐Mokrani, Luis A. Córdova, Bénédicte Brulin, Dominique Heymann, Philippe Hulin, Steven Nedellec, Eléna Ishow
Journal: Advanced Healthcare Materials (2015)

Strongly solvatochromic fluorophores are devised, containing alkyl chains and enable to self‐assemble as very bright fluorescent organic nanoparticles (FONs) in water ( Φ f = 0.28). The alkyl chains impart each fluorophore with strongly hydrophobic surroundings, causing distinct emission colors between FONs where the fluorophores are associated, and their disassembled state. Such color change is harnessed to assess the long‐term fate of FONs in both cancer cells and monocytes/macrophages. Disintegration of the orange‐emitting FONs by monocytes/macrophages is evidenced through the formation of micrometer green‐yellowish emitting vesicles. By contrast, cancer cells retain longer the integrity of organic nanoparticles. In both cases, no significant toxicity is detected, making FONs as valuable bioimaging agents for cell tracking with weak risks of deleterious accumulation and low degradation rate.
Lack of relation between glycosylated haemoglobin concentrations and number of daily insulin injections: cross sectional study in care of ambulatory diabetes.
Authors: C D Agardh, G Tallroth
Journal: BMJ (1985)

Diabetic treatment aims at achieving a normal blood glucose concentration as reflected by the glycosylated haemoglobin concentration. Intensive treatment by insulin pump or multiple insulin injections is thought to achieve this. In an unselected group of outpatient diabetics metabolic control was the same after one, two, three, or more injections, which suggests that the mode of treatment was optimal for each group.
Blood concentrations of dihydroxylated vitamin D metabolites after an oral dose.
Authors: R S Mason, D Lissner, S Posen, A W Norman
Journal: BMJ (1980)

Postpartum haemolytic-uraemic syndrome successfully treated with antithrombin III Since first described in 1966 the acute postpartum haemolyticuraemic syndrome (HUS) has been reported in over 40 cases by various authors.'In view of the poor prognosis despite treatment with dialysis, immunosuppression and heparin, streptokinase, dipyridamol, acetylsalicylic acid, or corticosteroids, alone or combined, we report a case in which treatment with a concentrate of antithrombin III (AT-III) appeared to cure the haemolytic anaemia and the thrombo- cytopenia rapidly, normalise kidney function within a few days, and prevent irreversible kidney damage. Case reportA 34-year-old primipara was admitted to hospital in the eighth month of pregnancy because of a slightly raised blood pressure (150/100 mm Hg) and proteinuria (1-5-4 g/24 h).Thirty hours before delivery her serum creatinine was 277 ,umol/l (3-1 mg/100 ml).Four days after admission labour began spontaneously and was completed in 70 minutes without complications.
Systemic inflammation in absence of gut bacterial translocation in C57BL/6 mice with cirrhosis
Authors: María Úbeda, Margaret Lario, Leticia Muñoz, David Díaz, María José Borrero, Laura García-Bermejo, Melchor Álvarez-Mon, Agustín Albillos
Journal: Gut (2012)

We read with interest the article by Wiest et al about spontaneous bacterial peritonitis guidelines.1 The authors point out the relevance of pathological bacterial translocation (BT) from the gut to mesenteric lymph nodes (MLN) as the pathophysiological hallmark of spontaneous bacterial peritonitis in cirrhosis, and the need of further research in the factors involved in BT. The study of BT, ascites and related immune system abnormalities in carbon tetrachloride (CCl4) cirrhosis is usually conducted in rats. This model has proved useful for research into the pathogenesis and role of the systemic pro-inflammatory response associated with cirrhosis and its link to BT.2–4 We recently showed that modulation of the immune system response in cirrhotic rats …
Reduced Cognition in Syngap1 Mutants Is Caused by Isolated Damage within Developing Forebrain Excitatory Neurons
Authors: Emin D. Ozkan, Thomas K. Creson, Enikö A. Kramár, Camilo Rojas, Ron R. Seese, Alex H. Babyan, Yulin Shi, Rocco Lucero, Xiangmin Xu, Jeffrey L. Noebels, Courtney A. Miller, Gary Lynch, Gavin Rumbaugh
Journal: Neuron (2014)