tbuckley/cabot-search huggingface dataset:
The potential role of bronchial challenge testing to identify overtreatment of community managed asthma
Authors: Arvind Manoharan, Brian Lipworth, Elizabeth Craig, Cathy Jackson
Journal: European Respiratory Journal (2014)

Introduction: Bronchial hyperresponsiveness is a defining feature of asthma and is measured by bronchial challenges which are not routinely used in primary care.

Aim: To evaluate the potential role of direct (methacholine) and indirect (mannitol) challenge testing in primary care.

Methods: Community managed asthmatics were identified by the Health Informatics Centre (HIC) and invited to take part in the study. At screening the following tests were carried out: spirometry, methacholine and mannitol challenge; FeNO, Asthma Control Questionnaire (ACQ-6) and Asthma Quality of Life Questionnaire (MiniAQLQ).

Results: 3388 asthmatics were identified by HIC with 423 positive responses and 123 completing the study. 70% had either a positive methacholine (PC20<8mg/ml) or mannitol challenge (PD15<635mg) and 30% were non-responsive to both challenges. 14% of methacholine responders were negative to mannitol and 16% of mannitol responders were negative to methacholine. Spirometry, FeNO, ACQ and AQLQ were significantly better in the non-responder group who were exposed to high ICS dose and frequent LABA.

View this table:

Patient characteristics according to bronchial challenge response





Conclusions: We found that 30% of patients with community managed asthma were challenge negative and also appeared to be overtreated, in turn suggesting the need for supervised step-down.
Association of the Type of Toy Used During Play With the Quantity and Quality of Parent-Infant Communication
Authors: Anna V. Sosa
Journal: JAMA Pediatrics (2015)

The early language environment of a child influences language outcome, which in turn affects reading and academic success. It is unknown which types of everyday activities promote the best language environment for children.To investigate whether the type of toy used during play is associated with the parent-infant communicative interaction.Controlled experiment in a natural environment of parent-infant communication during play with 3 different toy sets. Participant recruitment and data collection were conducted between February 1, 2013, and June 30, 2014. The volunteer sample included 26 parent-infant (aged 10-16 months) dyads.Fifteen-minute in-home parent-infant play sessions with electronic toys, traditional toys, and books.Numbers of adult words, child vocalizations, conversational turns, parent verbal responses to child utterances, and words produced by parents in 3 different semantic categories (content-specific words) per minute during play sessions.Among the 26 parent-infant dyads, toy type was associated with all outcome measures. During play with electronic toys, there were fewer adult words (mean, 39.62; 95% CI, 33.36-45.65), fewer conversational turns (mean, 1.64; 95% CI, 1.12-2.19), fewer parental responses (mean, 1.31; 95% CI, 0.87-1.77), and fewer productions of content-specific words (mean, 1.89; 95% CI, 1.49-2.35) than during play with traditional toys or books. Children vocalized less during play with electronic toys (mean per minute, 2.9; 95% CI, 2.16-3.69) than during play with books (mean per minute, 3.91; 95% CI, 3.09-4.68). Parents produced fewer words during play with traditional toys (mean per minute, 55.56; 95% CI, 46.49-64.17) than during play with books (mean per minute, 66.89; 95% CI, 59.93-74.19) and use of content-specific words was lower during play with traditional toys (mean per minute, 4.09; 95% CI, 3.26-4.99) than during play with books (mean per minute, 6.96; 95% CI, 6.07-7.97).Play with electronic toys is associated with decreased quantity and quality of language input compared with play with books or traditional toys. To promote early language development, play with electronic toys should be discouraged. Traditional toys may be a valuable alternative for parent-infant play time if book reading is not a preferred activity.
Angiotensin II-induced superoxide anion generation in human vascular endothelial cells Role of membrane-bound NADH-/NADPH-oxidases
Authors: H Zhang
Journal: Cardiovascular Research (1999)

Angiotensin II (ANG II) mediated hypertension accelerates atherosclerosis (AS) and thereby increases the incidence of myocardial infarction (MI). On the other hand, superoxide anion (O2-) is involved in the modification of low density lipoproteins, inhibition of prostacyclin (PGI2) formation and breakdown of nitric oxide. These events finally lead to rapid progression of AS and MI. In the present study, we investigate whether ANG II can induce O2- release from human vascular endothelial cells (HVECs) and the possible mechanisms involved.The expression of ANG receptors subtype-1 (AT-1) and subtype-2 (AT-2) were identified by using reverse transcription polymerase chain reaction and sequence analysis. The O2- production was dose-dependently increased in HVECs treated with ANG II (10(-7)-10(-9) M) and with a maximum rate after 1 h of incubation. This event was significantly inhibited by pretreatment of cells with the specific AT-1 blocker losartan (10(-7) M) and to a lesser extent by the specific AT-2 receptor blocker PD123319 (10(-7) M). The combined incubation of both receptor blockers was even more effective. In addition, our lucigenin-enhanced chemiluminescence assay showed that the activity of plasma membrane-bound NADH-/NADPH-oxidases derived from ANG II-treated cells was also significantly increased, this effect was reduced in cells pretreated with losartan or to lesser extent by PD123319. However, the activity of xanthine oxidase remained unchanged in response to ANG II. Furthermore, the basal O2- release from HVECs was inhibited in cells treated with angiotensin-converting enzyme (ACE) inhibitor, Lisinopril (10(-6) M), and this event could be reversed by ANG II.ANG II induces O2- release in HVECs via activation of membrane-bound NADH-/NADPH-oxidase, an effect, that is mediated by both AT-1 and AT-2 receptors. This suggests that acceleration of AS and MI in ANG II-mediated hypertension may at least be due to ANG II-induced O2- generation from vascular endothelial cells. In this case, the ACE inhibitors and the ANG receptor antagonists may act as causative "antioxidants".
Chemical exposure and lung function in the fragrance industry: A multi-site cross-sectional study
Authors: Garry Dix
Journal: European Respiratory Journal (2012)

INTRODUCTION 

Fragrance production employees are exposed to large quantities of chemical mixtures, at exposure levels significantly higher than the final consumer.

AIMS AND OBJECTIVES 

To answer the research question:

In fragrance industry employees, is occupational respiratory exposure to chemicals linked to a reduction in lung function? 

METHODS 

A cross-sectional study was designed, using an exposed group (fragrance production) and a control group (non-exposed industry employees). 5 UK fragrance companies took part, total sample size was 112 (exposed n=60, controls n=52), calculated as sufficient to achieve 80% power and 5% significance. Spirometric measurements (FEV1, FVC, PEF) were taken pre- and post-shift, and cross-shift decline was calculated. Questionnaires were completed regarding potential confounding factors (smoking, body mass index, personal or family history of respiratory problems). Analysis of covariance (ANCOVA) was performed using the statistical package SPSS (v18).

RESULTS 

Adjusted mean difference between groups (exposed vs. control) for each outcome was not observed to be statistically significant (table below).

Family history of respiratory problems was observed to have a significant effect on PEF (p=0.043).

View this table:

Adjusted mean differences between Exposed and Control groups*





CONCLUSIONS 

Occupational respiratory exposure to chemicals used in fragrance production did not have a significant effect on lung function.
Acquired Chromosome 11q Deletion Involving the Ataxia Teleangiectasia Locus in B-Cell Non-Hodgkin’s Lymphoma: Correlation With Clinicobiologic Features
Authors: Antonio Cuneo, Renato Bigoni, Gian Matteo Rigolin, Maria Grazia Roberti, Raffaella Milani, Antonella Bardi, Claudia Minotto, Paola Agostini, Cristiano De Angeli, Maria Grazia Narducci, Silvia Sabbioni, Giandomenico Russo, Massimo Negrini, Gianluigi Castoldi
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To study the clinicobiologic significance of acquired 11q deletions involving the ataxia teleangiectasia locus (ATM+/−) in B-cell non-Hodgkin’s lymphomas (NHL). PATIENTS AND METHODS: Fifty-three indolent lymphomas and 82 aggressive lymphomas were studied by conventional cytogenetic analysis and by fluorescence in situ hybridization using an 11q22–23 probe recognizing ATM sequences. Pertinent clinical data were collected. RESULTS: A hemizygous ATM deletion was seen in 44% to 88% of the interphase cells in 15 cases (11.1%); four patients had an indolent lymphoma (follicular center cell lymphoma), and 11 patients had an aggressive lymphoma (five mantle-cell lymphomas [MCLs] and six diffuse large-cell lymphomas). Dual-color hybridization studies showed ATM deletion to be possibly a secondary aberration in three patients with MCL. Ten out of 15 ATM+/− patients had a complex karyotype, 11 out of 15 had more than 90% abnormal metaphases (AA karyotype status), and +12, 13q14 deletion, and 17p13 deletion were seen in seven, four, and five cases, respectively. Patients with ATM+/− more frequently had a complex karyotype (P = .01) and the AA karyotype (P = .04) compared with patients without ATM+/−. With the exception of a poor performance status (P = .001), no correlation was found between ATM+/−, initial clinical variables, and complete remission rate; whereas a highly significant association was found with shorter survival (P &lt; .0001). This cytogenetic lesion maintained its prognostic importance in multivariate analysis (P = .0004), along with performance status (P = .0006), serum lactate dehydrogenase level (P = .03), splenomegaly (P = .01), and histologic grade (P = .03). When analyzing indolent lymphomas and aggressive lymphomas separately, ATM+/− maintained its prognostic importance as an independent variable in both histologic groups (P = .0001 and P = .016, respectively). CONCLUSION: Though possibly not representing a primary genetic lesion in the majority of cases, the acquired ATM+/− status has clinicobiologic importance in NHL, possibly representing a major cytogenetic determinant of outcome.
Therapeutic efficacy of silibinin on chemically-induced mouse lung tumors
Authors: Lori Dwyer-Nield, Rana Singh, Alpna Tyagi, Alvin Malkinson, Rajesh Agarwal
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4969 

Silibinin, a flavanone from milk thistle, inhibits the growth of tumors in several chemically-induced rodent models, including mouse lung. We previously showed that dietary silibinin markedly reduced growth, progression, and angiogenesis of urethane-induced lung tumors in A/J mice when fed to mice 2 weeks after carcinogen administration in a model of chemoprevention. To determine whether silibinin could also act as a chemotherapeutic agent in this system, we examined the effects of silibinin treatment on established mouse lung tumors. A/J mice, injected with urethane (1 mg/g body weight), were allowed to develop lung tumors for 33 wks. Tumors at this stage have characteristics of a malignant phenotype, i.e. they are invasive, exhibit nuclear dysmorphology, and are heterogeneous in appearance. Silibinin (or the vehicle control) was then administered by gavage (5 days/week, 742 mg/kg, a dose determined to be equivalent to the 1% wt./wt. dietary dose previously shown to be effective) for 10 wks. When mice were sacrificed and their lung tumor number and burden determined, those mice receiving silibinin by gavage had 33% fewer tumors and 37% less tumor burden (pooled tumor wt/mouse) than mice receiving vehicle. Immunohistochemical analysis of fixed lungs showed that silibinin-treated mice had 62% fewer PCNA positive cells compared to the vehicle-treated controls, indicating that silibinin decreased tumor cell proliferation. Tumor microvessel density (as determined by counting CD31 positive cells in tumors), an indicator of neovasularization, decreased by 67% in silibinin-treated mice over controls. There was 72% less COX-2 expression in tumors, an enzyme associated with lung neoplasia and angiogenesis, in silibinin-treated mice. These results indicate that silibinin is effective in slowing the growth of, and perhaps stimulating regression of, established mouse lung tumors. This implies that dietary silibinin may be useful in preventing the neoplastic progression of early lesions in humans. This work was supported by CA 33497 and CA113876.
Expression of A-myb, but not c-myb and B-myb, is restricted to Burkitt's lymphoma, sIg+ B-acute lymphoblastic leukemia, and a subset of chronic lymphocytic leukemias
Authors: J Golay, M Luppi, S Songia, C Palvarini, L Lombardi, A Aiello, D Delia, K Lam, DH Crawford, A Biondi, T Barbui, A Rambaldi, M Introna
Journal: Blood (1996)
Paresis Acquired in the Intensive Care Unit&lt;SUBTITLE&gt;A Prospective Multicenter Study&lt;/SUBTITLE&gt;
Authors: Bernard De Jonghe, Tarek Sharshar, Jean-Pascal Lefaucheur, François-Jérome Authier, Isabelle Durand-Zaleski, Mohamed Boussarsar, Charles Cerf, Estelle Renaud, Francine Mesrati, Jean Carlet, Jean-Claude Raphaël, Hervé Outin, Sylvie Bastuji-Garin
Journal: JAMA (2002)

ContextAlthough electrophysiologic and histologic neuromuscular abnormalities are common in intensive care unit (ICU) patients, the clinical incidence of ICU-acquired neuromuscular disorders in patients recovering from severe illness remains unknown.ObjectivesTo assess the clinical incidence, risk factors, and outcomes of ICU-acquired paresis (ICUAP) during recovery from critical illness in the ICU and to determine the electrophysiologic and histologic patterns in patients with ICUAP.DesignProspective cohort study conducted from March 1999 to June 2000.SettingThree medical and 2 surgical ICUs in 4 hospitals in France.ParticipantsAll consecutive ICU patients without preexisting neuromuscular disease who underwent mechanical ventilation for 7 or more days were screened daily for awakening. The first day a patient was considered awake was day 1. Patients with severe muscle weakness on day 7 were considered to have ICUAP.Main Outcome MeasuresIncidence and duration of ICUAP, risk factors for ICUAP, and comparative duration of mechanical ventilation between ICUAP and control patients.ResultsAmong the 95 patients who achieved satisfactory awakening, the incidence of ICUAP was 25.3% (95% confidence interval [CI], 16.9%-35.2%). All ICUAP patients had a sensorimotor axonopathy, and all patients who underwent a muscle biopsy had specific muscle involvement not related to nerve involvement. The median duration of ICUAP after day 1 was 21 days. Mean (SD) duration of mechanical ventilation after day 1 was significantly longer in patients with ICUAP compared with those without (18.2 [36.3] vs 7.6 [19.2] days; P = .03). Independent predictors of ICUAP were female sex (odds ratio [OR], 4.66; 95% CI, 1.19-18.30), the number of days with dysfunction of 2 or more organs (OR, 1.28; 95% CI, 1.11-1.49), duration of mechanical ventilation (OR, 1.10; 95% CI, 1.00-1.22), and administration of corticosteroids (OR, 14.90; 95% CI, 3.20-69.80) before day 1.ConclusionsIdentified using simple bedside clinical criteria, ICUAP was frequent during recovery from critical illness and was associated with a prolonged duration of mechanical ventilation. Our findings suggest an important role of corticosteroids in the development of ICUAP.
Cerebral dysfunction after water pollution incident in Camelford
Authors: A. David
Journal: BMJ (2000)

Editor—Altmann et al's results on a group of litigants were published almost 10 years after the water pollution incident in Camelford.1 Although they acknowledge competing interests, they overlook the main problem—the bias inherent in self selection of cases.

The cases may have already had unexplained symptoms and cognitive problems, the incident serving to focus attention on a possible cause. The results show significant impairment in neuropsychological and neurophysiological tests among the cases, which the authors argue must be the result of prolonged toxicity to acute exposure to aluminium in drinking water. Neuropsychological tests are assumed to be objective, automated, computerised, and quantitative, but they do require the conscious effort of subjects. Those complaining of poor memory and concentration are given a test that requires both, so performance cannot be taken at face value. Subjects are not carrying out a deliberate deception, but their performance like everyone else's is influenced by the context. Similarly, the choice of relatives as controls is unfortunate. Out of loyalty, they will tend to give more than their best, thus widening the gulf in performance.

Sensory evoked potentials are less liable to such effects. The authors report an increased latency in “flash minus pattern” evoked potential (EP), an index of cognitive impairment in patients with Alzheimer's disease and aluminium related dialysis dementia. Their data are inadequate for evaluating this finding since neither the raw latencies for the controls nor the waveforms for the cases are given. The results hang on the difference between patterned visual evoked potentials (VEPs) and flash EPs. The VEP is also known as the P100 since it occurs reliably 100 ms after the onset of the stimulus. The response to flash is characteristically longer, by around 20 ms in normal subjects, more in those with brain disorders.2,3 The table compares results in four groups.1–4 It shows that the latency of the flash EP is not prolonged in the Camelford cases but that the increased difference between the two measures is accounted for by the apparent quickening of the patterned VEP. The most parsimonious explanation for this unphysiological result is a calibration error and wandering baseline. 

The reopening of the Camelford case is regrettable as the people concerned may worry anew about their health. Wessely and I recommended that incidents such as these should trigger a rapid response by public health professionals to gather complete data before litigation, media attention, and local fears distort health perception.5 It seems that such lessons have still to be learnt.
Summative assessment for general practitioner registrars
Authors: J. Bahrami
Journal: BMJ (1995)

initial marking, it is impossible to sit beside one's coexaminer for 30 minutes without forming a (usually accurate) impression of what the co- examiner's mark is likely to be.All of these factors would tend to increase the interexaminer agreement but not necessarily increase the reliability of the vivas.A more thorough analysis would enable us to judge whether the commonly held view that vivas are inherently unreliable can now be revised.
Tumor-directed PET imaging of bone metastases in metastatic castration-resistant prostate cancer (mCRPC) using Zr-89 labeled anti-prostate specific membrane antigen (PSMA) antibody J591.
Authors: Michael J. Morris, Neeta Pandit-Taskar, Scott T. Tagawa, David M. Nanus, Stephen Barnett Solomon, Jorge A. Carrasquillo, Victor E. Reuter, Jason Stuart Lewis, Volkan Beylergil, Joseph A. O' Donoghue, Serge K. Lyashchenko, Danny F. Martinez, Kristen Rebecca Curtis, Jeremy C. Durack, Sarah M. Cheal, Neil Harrison Bander, Howard I. Scher, Steven M. Larson
Journal: Journal of Clinical Oncology (2014)

25 Background: There is no standard imaging modality that specifically and accurately images prostate cancer metastases, hampering assessments of tumor distribution, prognostication, and response. J591 is a humanized antibody that targets the external domain of PSMA, which is copiously expressed in metastatic disease and upregulated in mCRPC. We have previously reported on the feasibility, and PK and biodistribution properties of Zr-89-J591 in 10 patients (Morris et al, GU ASCO 2013). We now report on the targeting/accuracy in 49 patients with mCRPC. Methods: Following standard CT/MRI, bone scintigraphy, and FDG PET imaging, 5 mCi of Zr-89-J591 was administered intravenously. Zr-89-J591 was imaged 6-8 days after injection. Positive scan findings were confirmed, where possible, with biopsies in the following preference: Zr-89-J591 and FDG positivity, then Zr-89-J591 and FDG mismatch, and lastly standard imaging and any PET mismatch. Results: A total of 535 unique bone lesions in 49 patients were identified using all imaging modalities. 339 (63%) of these were evident on bone scans, 302 (56%) on CT, 202 (38%) on FDG PET, and 490 (92%) on Zr-89-J591 PET. The concordance between bone scans and Zr-89-J591 was 303/490 (62%). 102 sites were seen only on Zr-89-J591 and not on any other imaging modality. 44 biopsies were performed from 33 patients; 21 of those biopsies were bone. The histopathologic correlation for bone is provided in the table below. All positive biopsies were J591 positive (16/16); sensitivity of J591 was =100%, and positive predictive value (16/18) was 89%. Conclusions: Imaging using J591 PET/CT detects bone disease at greater rates than any other imaging modality tested. Biopsy data of J591 positive lesions suggest that most J591 positive lesions represent biopsy confirmed prostate metastasis. We are now testing minibodies based on J591 that may target faster, offering a more favorable imaging schedule. Clinical trial information: NCT01543659. [Table: see text]
CORRECTION
Authors: G Longo, E Panontin, G Ventura
Journal: Thorax (2009)

Henderson and colleagues1 interestingly describe six different wheezing phenotypes among which persistent wheeze is, they say, less associated with atopy than intermediate or late-onset wheeze (but with similar lung function deficits, suggesting a mixture of structural airway abnormalities and atopic wheeze).

We would like to emphasise the fact that children with persistent asthma without allergic sensitisation (ie, non-atopic …