tbuckley/cabot-search huggingface dataset:
Late-breaking abstract: Does a relationship exist between mean platelet volume and left ventricular function in children with obstructive sleep apnea syndrome?
Authors: Afroditi Sakellaropoulou, Andreas Giannopoulos, Katerina Haidopoulou, Maria Emporiadou, Maria Hatzistilianou
Journal: European Respiratory Journal (2014)

Mean platelet volume (MPV), the most commonly used measure of platelet size, is a potential marker of platelet reactivity. Previous studies have reported increased platelet activation and aggregation in patients with obstructive sleep apnea syndrome (OSAS). Left ventricle hypertrophy (LVH) was defined as an Interventricular Septal Thickness at Diastole >12 mm.  The aim of this study was to test if high MPV is associated with impaired cardiopulmonary function in children with OSAS.  18 children with symptoms suggestive of OSAS were recruited. OSAS was verified with Sleep polysomnography. Blood samples were collected for measurements of MPV and other laboratory data. Doppler echocardiography was also assessed.  Seven children (36.8%) had mild, 7 (36.8%) moderate and 5 (26.3%) had severe degree of OSAS. One child only had LVH and 12 (63.15%) had increased MPV.  A positive correlation between MPV and BMI z score (p=0.019, r=0.548) was recorded, while a negative correlation exists between MPV and Apnea Hypopnea Index (p=0.590, r= - 0.136) and Apnea Index (p=0.259, r= - 0.281).  Statistical importance difference was only found between MPV and left ventricular internal dimension z score during systole (LVIDs z score, p=0.05), but not with LVID z score during diastole (p=0.821), left ventricle internal dimension in diastole z score (LVPWd z score, p=0.159) and left ventricular posterior wall dimension during systole z score (LVPWs z score, p=0.481).  In conclusion, it appears that a relation probably exists between MPV, left ventricular internal dimensions, obesity, and OSAS, but further studies are required to establish it.
Rhinovirus infection and asthma symptoms in a longitudinal cohort of Australian children
Authors: Sacha Stelzer-Braid, Christiana Willenborg, Brett Toelle, Frances Garden, Adam Jaffe, Roxanne Strachan, Yvonne Belessis, Brian Oliver, Helen Reddel, Guy Marks, William Rawlinson, Euan Tovey
Journal: European Respiratory Journal (2014)

Aims.  Viral infections are the main cause of exacerbations and acute hospital admissions in children with asthma. Little is known about viruses circulating in the community and their impact on day-to-day fluctuation of asthma symptoms.We hypothesised that such infections would be associated with increased symptoms.   Methods.  67 children, aged 5-12, with moderate asthma, were recruited from a High Risk Asthma Clinic or Emergency Department. They self-collected nasal wash and exhaled breath samples and recorded asthma and cold symptoms and lung function, twice a week for 10 weeks. The presence of 8 viruses, including human rhinovirus (hRV), was analysed by PCR and sequencing. A mixed model, to account for repeated measures, was used to determine the current and delayed impact of viruses on symptoms and lung function.   Results. 25.5% of nasal samples and 11.5% of breath samples were hRV positive; only 1.8% were positive for other viruses. With genotyping (56% of positive samples), 58.0% were hRV-A positive, 22.7% were hRV-B positive and 19.2% were hRV-C positive. The presence of hRV in nasal wash, but not in breath, was associated with the presence of symptoms; adjusted odds ratios: cough 2.53 (95%CI 1.62-3.94), wheeze 3.05 (1.89-4.93), self-report fever 2.07 (1.17-3.64) and coryzal symptoms 1.95 (1.14-3.32) over the previous 3-4 days. These associations remained 3-4 days later, but generally not 7 days later.   Conclusions: In a 10-week study of children with moderate asthma, the presence of hRV in nasal wash, but not in exhaled breath, was associated with mild worsening of day-to-day cold and asthma symptoms for up to a week.   Support:  NHMRC Project Grant 633238.
Ability of IGRAs for diagnosis of tuberculosis infection in adolescents, and role of non-tuberculous mycobacteria in the positivity of tuberculine skin test
Authors: Irene Mialdea, Irene Latorre, Empar Giner, Nuria Díez, Carme Salazar, Antonio Salazar, Jose Domínguez, Amparo Escribano
Journal: European Respiratory Journal (2011)

Introduction: A big drawback of tuberculin skin test (TST) is the cross-reaction with bacillus Calmette-Guerin (BCG) vaccine or with non-tuberculous mycobacteria (NTM). In this way, interferon-gamma release assays (IGRAs) are more specific but few data are available for children.  Aims and objectives: To assess the ability of IGRAs to detect Mycobacterium tuberculosis infection in healthy adolescents, and to know the influence of previous NTM sensitisation in discordant results as positive TST with negative IGRA.  Methods: TST was performed on 2,346 students aged 12-16 from Valencia city during the 2009-10 academic year. Those with TST ≥5 mm, underwent a checkup, a chest x-ray and QuantiFERON-TB GOLD In-Tube (QFT) test. Those with negative QFT, were tested by T-SPOT.TB (TSPOT) and T cells were stimulated with Mycobacterium avium sensitin (MAS).  Results: TST was ≥5 mm in 171 students (4.3%), and QFT was tested in 159. QFT was positive in 33 (21%) and it enabled to diagnose 10 individuals BCG-immunized with latent infection. QFT was negative in the 4 students with radiographic findings of previous tuberculosis (TB), and also in 14 from the 17 diagnosed with active TB. From those with negative QFT (126), TSPOT was tested in 95; it was positive in 5 (2 had been classed as vaccine reactions). Stimulation with MAS was positive in 15 (5 were not vaccinated and TSPOT was negative in all of them).  Conclusions: IGRAs help to detect infection in BCG-immunized, and to rule it out in doubtful cases, avoiding unnecessary treatments. Previous NTM sensitisation may explain some positive TSTs in non-vaccinated.  This work is supported by EVES and SENP grants
Medicolegal Consequences of Postoperative Intra-Abdominal Adhesions
Authors: Harold Ellis
Journal: Journal of the Royal Society of Medicine (2001)

Postoperative adhesions are an almost invariable consequence of abdominal and pelvic surgery. Their most important morbidity is small-bowel obstruction, but other sequelae include female infertility and dyspareunia and increased risk of visceral injury at subsequent laparotomy or laparoscopy. Whether chronic abdominal pain is truly a consequence of adhesions is debatable, although it is likely to be accepted as an entity by both patients and their legal advisors. Of 14 successful claims dealt with by a British medical defence organization, 5 were for perforations after laparoscopic division of adhesions, 2 for adhesions after laparoscopic surgery, 1 for infertility as a result of adhesions and 6 for delayed diagnosis of obstruction. General practitioners, surgeons and gynaecologists need to be aware of the increasing burden of medicolegal claims arising from these complications.
Prognostic value of immunophenotypic detection of minimal residual disease in acute lymphoblastic leukemia.
Authors: J Ciudad, J F San Miguel, M C López-Berges, B Vidriales, B Valverde, M Ocqueteau, G Mateos, M D Caballero, J Hernández, M J Moro, M V Mateos, A Orfao
Journal: Journal of Clinical Oncology (1998)

PURPOSE The identification of immunophenotypic aberrancies through multiparametric flow cytometry makes the differentiation between normal and leukemic cells relatively simple and quick, and is therefore an attractive method for the investigation of minimal residual disease (MRD). In this report, we have analyzed the impact on relapse and relapse-free survival (RFS) of detecting immunophenotypical aberrant cells in acute lymphoblastic leukemia (ALL) patients in cytomorphologic complete remission (CR). MATERIALS AND METHODS Two hundred eleven bone marrow (BM) samples from 53 consecutive ALL (37 precursor B-ALL and 16 T-ALL) patients were analyzed. The only selection criteria were to have at least one aberrant immunophenotypic feature at diagosis and to have achieved cytomorphologic CR after induction therapy. For MRD detection, all follow-up samples were analyzed with triple labelings using a two-step acquisition procedure, in which 106 cells were screened for the possible persistence of residual leukemic cells with the same phenotypic aberrancy as that identified diagnosis. RESULTS Patients who displayed a gradual increase in MRD levels showed a higher relapse rate (90% v22%; P &lt; .00001) and shorter median RFS (12 months v not reached; P &lt; .0001) than those with stable or decreasing MRD levels. This adverse prognostic influence also was observed when children and adults, as well as B-ALL and T-ALL patients, were analyzed separately. An MRD level &gt; or = or greater than 10(-3) discriminated two risk groups of ALL patients with significantly different relapse rates and RFS at all treatment phases (end of induction, consolidation, maintenance, and out of treatment). CONCLUSION Multiparametric flow cytometry of MRD in ALL patients is a valuable tool for relapse prediction and for the identification of a cohort of patients with very poor prognosis.
Combined BRAF and MEK Inhibition With Dabrafenib and Trametinib in <i>BRAF</i> V600–Mutant Colorectal Cancer
Authors: Ryan B. Corcoran, Chloe E. Atreya, Gerald S. Falchook, Eunice L. Kwak, David P. Ryan, Johanna C. Bendell, Omid Hamid, Wells A. Messersmith, Adil Daud, Razelle Kurzrock, Mariaelena Pierobon, Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, Yuchen Bai, Kiran Patel, Alan P. Venook, Scott Kopetz
Journal: Journal of Clinical Oncology (2015)

To evaluate dabrafenib, a selective BRAF inhibitor, combined with trametinib, a selective MEK inhibitor, in patients with BRAF V600-mutant metastatic colorectal cancer (mCRC).A total of 43 patients with BRAF V600-mutant mCRC were treated with dabrafenib (150 mg twice daily) plus trametinib (2 mg daily), 17 of whom were enrolled onto a pharmacodynamic cohort undergoing mandatory biopsies before and during treatment. Archival tissues were analyzed for microsatellite instability, PTEN status, and 487-gene sequencing. Patient-derived xenografts were established from core biopsy samples.Of 43 patients, five (12%) achieved a partial response or better, including one (2%) complete response, with duration of response > 36 months; 24 patients (56%) achieved stable disease as best confirmed response. Ten patients (23%) remained in the study > 6 months. All nine evaluable during-treatment biopsies had reduced levels of phosphorylated ERK relative to pretreatment biopsies (average decrease ± standard deviation, 47% ± 24%). Mutational analysis revealed that the patient achieving a complete response and two of three evaluable patients achieving a partial response had PIK3CA mutations. Neither PTEN loss nor microsatellite instability correlated with efficacy. Responses to dabrafenib plus trametinib were comparable in patient-derived xenograft-bearing mice and the biopsied lesions from each corresponding patient.The combination of dabrafenib plus trametinib has activity in a subset of patients with BRAF V600-mutant mCRC. Mitogen-activated protein kinase signaling was inhibited in all patients evaluated, but to a lesser degree than observed in BRAF-mutant melanoma with dabrafenib alone. PIK3CA mutations were identified in responding patients and thus do not preclude response to this regimen. Additional studies targeting the mitogen-activated protein kinase pathway in this disease are warranted.
A Method for Predicting Malignant Tumor Destruction by Laser Radiation
Authors: John Peter Minton, Marvin Zelen
Journal: JNCI Journal of the National Cancer Institute (1965)

Using three separate experiments on the effect of laser radiation on two malignant tumor systems in experimental mice, a theory was developed for predicting the probability of tumor destruction from laser radiation. The probability of tumor kill appears to be a function of the ratio of laser energy to tumor area and also of a parameter which depends on the tumor system and its energy absorption characteristics in relation to the wavelength of the laser energy.
Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary diseases
Authors: Nuri Tutar, Gokhan Metan, A. Nedret Koc, Insu Yilmaz, Ilkay Bozkurt, Zuhal Ozer Simsek, Hakan Büyükoglan, Asiye Kanbay, F. Sema Oymak, Inci Gülmez, Ramazan Demir
Journal: European Respiratory Journal (2013)

The purpose of this study is to investigate the clinical and demographic characteristics and treatment responses of Invasive pulmonary aspergillosis (IPA) in patients with COPD. From January 2006 to December 2011, 71 patients with a positive culture of Aspergillus from lower respiratory tract samples were examined. Of these patients, 11 (15.4%) had IPA with grade 3 or 4 COPD. Aspergillus hyphae was detected in the lung biopsy in three (27.3%) of 11 and defined as proven IPA; the pathological sample was not taken in the other eight (72.7%) patients, and these were defined as probable IPA. Aspergillus isolates were identified as six Aspergillus fumigatus and three Aspergillus niger in nine patients. Patients were diagnosed as IPA 13.8 ± 3.8 days after admission. While five patients required intensive care unit admission, four of them received mechanical ventilation. The most common symptom was dyspnea (n=11, 100%). Positive results of serum galactomannan assays were detected in nine patients (81.8%). The most common finding on chest X-ray and computed tomography (CT) (respectively 63.6%, 72.7%) was infiltration. Worsening radiological findings were observed in seven patients (63.6%). Amphotericin B was the initial drug of choice in all patients and five patients were discharged with oral voriconazole after amphotericin B therapy. Six patients (54.5%) died before treatment was completed. As a conclusion, IPA should be the part of the differential diagnosis particularly in patients with severe and very severe COPD presenting with dyspnea exacerbation, poor clinical status, and a new pulmonary infiltrate under broad-spectrum antibiotics and steroids.
Detection of changes in mortality after heart surgery
Authors: S. Gallivan, J. Lovegrove, C. Sherlaw-Johnson, J D Poloniecki
Journal: BMJ (1998)

Editor—We are concerned about the graphical technique described by Poloniecki et al in their analysis of perioperative mortality rates associated with cardiac surgery.1 Figure 2 shows three traces: observed mortality performance bracketed by control limits and plotted against the number of successive cases performed. The interpretation of the middle of the traces is straightforward since it is simply a variable life adjusted display that has previously been described and will be familiar to many cardiac surgeons in the United Kingdom.2 The use of control limits, on the other hand, is new. However, the usefulness and indeed the validity of these is not clear. As the authors themselves note, their analysis does not amount to a formal test of significance since the control limits have not been corrected for multiple testing; this is a major deficiency. The use of 99% control limits rather than 95% control limits presumably increases their separation and makes them more forgiving. It is not clear which level of significance should be used, a difficulty compounded by the fact that the limits are not based on formal significance testing.

If we understand correctly, these control limits have been calculated using a χ2 distribution. However, this fails to take into account case mix and heterogeneity of risk, the very things for which variable life adjusted display plots are used. The following example illustrates the danger in ignoring case mix when estimating ranges of variability. Consider operations on two sequences of 1000 patients with different underlying mortality risks that have been assessed preoperatively (table). Based on the given mortality risks, there is a 99% probability that the number of deaths that actually occur would fall in the range shown in the last column. These ranges are derived from exact calculations based on the binomial expansion. Using a χ2 distribution would give a range (16 to 44) close to the exact values obtained for the patients in sequence 2, for whom no heterogeneity of risk is present, but would substantially overestimate the range for the patients in sequence 1, for whom risks are heterogeneous. 

When examining surgical mortality, it is important to take case mix into account. However, this should be done not only when estimating the expected mortality but also when estimating the likely variability. Any overestimation of likely ranges of variability might well lead to undue complacency.
Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn's disease
Authors: T ten Hove
Journal: Gut (2002)

Background and aims: Treatment with infliximab induces remission in about 70% of patients with steroid refractory Crohn9s disease. Because Crohn9s disease is considered to be mediated by uncontrolled activation of mucosal T lymphocytes, we hypothesised that infliximab could induce apoptosis of T lymphocytes. Methods: Induction of apoptosis in vivo was studied in 10 patients with therapy refractory Crohn9s disease. In vitro, resting or stimulated Jurkat T cells were incubated with infliximab. Results: Infusion of infliximab (5 mg/kg) in steroid refractory patients with Crohn9s disease induced a clinical response in 9/10 patients but did not influence expression of activation markers, homing receptors, memory cells, Fas expression, or Bax/Bcl-2 expression on peripheral blood T lymphocytes. In contrast, a significant increase in CD3 and TUNEL positive cells within colonic biopsies was detected 24 hours after infusion of infliximab, suggesting that infliximab stimulates apoptosis of activated T lymphocytes but not of resting T cells. To test this hypothesis, the effects of infliximab on Jurkat T cells were investigated. We observed that infliximab induced apoptosis and an increase in the Bax/Bcl-2 ratio of CD3/CD28 stimulated Jurkat T cells but not of unstimulated Jurkat cells. Conclusions: Our data indicate that infliximab treatment causes a rapid and specific increase in apoptosis of T lymphocytes in the gut mucosa. These findings may explain the rapid and sustained therapeutic effects of infliximab in Crohn9s disease.
C-reactive protein at discharge, diabetes mellitus and ≥1 prior hospitalization predict early readmission in patients with acute exacerbation of chronic obstructive pulmonary disease
Authors: Ernesto Crisafulli, Arturo Huerta, Raúl Méndez, Mónica Guerrero, Raquel Martinez, Néstor Soler, Sanjay Sethi, Rosario Menéndez, Antoni Torres
Journal: European Respiratory Journal (2014)

Background  Recurrent hospitalizations in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients have clinical and economic consequences; particularly those readmitted soon after discharge. The aim of our observational study was to determine predictors of early readmission to hospital (30 days from discharge).  Methods  Prospective data on 125 hospitalized AECOPD patients were collected over a 30-month period at two Spanish university hospitals. Based on readmission after discharge, patients were divided into non-readmitted (n=96) and readmitted (n=29). Measures of serum inflammatory biomarkers were recorded on admission to hospital, at day 3 and at discharge; data on clinical, laboratory, microbiological and severity features were also recorded.  Results  In a multivariate model, C-reactive protein (CRP) at discharge ≥7.6 mg/L, presence of diabetes and ≥1 prior hospitalization for AECOPD were significant risk factors for predicting readmission. Presence of all 3 risk factors perfectly identified the readmitted patients (Area under curve-AUC of 1.000; 95% CI, 1.00-1.00; p  Conclusions  A combination of 3 readily available clinical and biochemical parameters is accurate in identifying hospitalized AECOPD patients at risk for early readmission.
Tumorigenesis in Athymic Nude Mouse Skin by Chemical Carcinogens and Ultraviolet Light234
Authors: Lucy M. Anderson, Jerry M. Rice
Journal: JNCI Journal of the National Cancer Institute (1987)

Journal Article Tumorigenesis in Athymic Nude Mouse Skin by Chemical Carcinogens and Ultraviolet Light Get access Lucy M. Anderson, Lucy M. Anderson Search for other works by this author on: Oxford Academic PubMed Google Scholar Jerry M. Rice Jerry M. Rice Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 78, Issue 1, January 1987, Pages 125–134, https://doi.org/10.1093/jnci/78.1.125 Published: 01 January 1987 Article history Received: 17 January 1986 Accepted: 21 July 1986 Published: 01 January 1987
Active Targeting of Sorafenib: Preparation, Characterization, and In Vitro Testing of Drug‐Loaded Magnetic Solid Lipid Nanoparticles
Authors: Agostina Grillone, Eugenio Redolfi Riva, Alessio Mondini, Claudia Forte, Lucia Calucci, Claudia Innocenti, Cesar de Julian Fernandez, Valentina Cappello, Mauro Gemmi, Stefania Moscato, Francesca Ronca, Rodolfo Sacco, Virgilio Mattoli, Gianni Ciofani
Journal: Advanced Healthcare Materials (2015)

Sorafenib is an anticancer drug approved by the Food and Drug Administration for the treatment of hepatocellular and advanced renal carcinoma. The clinical application of sorafenib is promising, yet limited by its severe toxic side effects. The aim of this study is to develop sorafenib-loaded magnetic nanovectors able to enhance the drug delivery to the disease site with the help of a remote magnetic field, thus enabling cancer treatment while limiting negative effects on healthy tissues. Sorafenib and superparamagnetic iron oxide nanoparticles are encapsulated in solid lipid nanoparticles by a hot homogenization technique using cetyl palmitate as lipid matrix. The obtained nanoparticles (Sor-Mag-SLNs) have a sorafenib loading efficiency of about 90% and are found to be very stable in an aqueous environment. Plain Mag-SLNs exhibit good cytocompatibility, whereas an antiproliferative effect against tumor cells (human hepatocarcinoma HepG2) is observed for drug-loaded Sor-Mag-SLNs. The obtained results show that it is possible to prepare stable Sor-Mag-SLNs able to inhibit cancer cell proliferation through the sorafenib cytotoxic action, and to enhance/localize this effect in a desired area thanks to a magnetically driven accumulation of the drug. Moreover, the relaxivity properties observed in water suspensions hold promise for Sor-Mag-SLN tracking through clinical magnetic resonance imaging.
Watchdog questions usefulness of UK’s £600m health and care regulators
Authors: Nigel Hawkes
Journal: BMJ (2015)

Regulation in healthcare costs £600m (€860m; $930m) a year in the United Kingdom and isn’t working well, concludes a new report from the Professional Standards Authority, which oversees the UK’s nine health and care professional regulatory bodies.1

The costs include the budgets of England’s Care Quality Commission (£211m a year) and corresponding bodies in Wales, Scotland, and Northern Ireland (£89m), £72m for Monitor, and the annual costs of the professional regulators, including the General Medical Council (£196m). The report rounds this up to “in the region of £600m” and adds: “If what was being assessed genuinely drove improvements in outcomes and quality …