tbuckley/cabot-search huggingface dataset:
Clinical atopy and associated factors in primary‐school pupils
Authors: J. Kuehr, T. Frischer, W. Karmaus, R. Meinert, R. Barth, R. Urbanek
Journal: Allergy (1992)

To investigate potential risk factors for clinical atopy in childhood, we obtained cross‐sectional data a cohort of 1376 8‐year‐old pupils. Parental atopy (hay fever, asthma, eczema), gestational age, maternal smoking habits, and the child's history of asthma, hay fever, and eczema were ascertained by questionnaire. Combining the history and the result of a skin prick test using seven aeroallergens, we defined the child's atopic diseases. Of the population evaluated, 25.4% were categorized as atopic (10.2% allergic asthma, 17.3% eczema, 6.9%, hay fever). As compared with the clear nonatopics (40.2%), parental atopic diseases were more prevalent in each of the atopic groups. Significant associations of the parents' and child's disease were obvious for eczema and hay fever. Low gestational age (LGA) was more frequent in children with any atopy or with an allergic asthma (odds ratio (OR) 1.7; 95% confidence interval (CI) 1.02–2.97; OR frequently in girls (OR 0.5; 95%, confidence interval 0.3–0.8; OR 0.6; 95% CI 0.4–0.9). In conclusion, our data underline the importance of parental atopy for the clinical outcome in the offspring. In addition, L GA appears to be a risk factor for allergic asthma and for general atopy in later life.
Tumoral Drug Metabolism: Overview and Its Implications for Cancer Therapy
Authors: M. Michael, M.M. Doherty
Journal: Journal of Clinical Oncology (2004)

Drug-metabolizing enzymes (DME) in tumors are capable of biotransforming a variety of xenobiotics, including antineoplastics, resulting in either their activation or detoxification. Many studies have reported the presence of DME in tumors; however, heterogenous detection methodology and patient cohorts have not generated consistent, firm data. Nevertheless, various gene therapy approaches and oral prodrugs have been devised, taking advantage of tumoral DME. With the need to target and individualize anticancer therapies, tumoral processes such as drug metabolism must be considered as both a potential mechanism of resistance to therapy and a potential means of achieving optimal therapy. This review discusses cytotoxic drug metabolism by tumors, through addressing the classes of the individual DME, their relevant substrates, and their distribution in specific malignancies. The limitations of preclinical models relative to the clinical setting and lack of data on the changes of DME with disease progression and host response will be discussed. The therapeutic implications of tumoral drug metabolism will be addressed—in particular, the role of DME in predicting therapeutic response, the activation of prodrugs, and the potential for modulation of their activity for gain are considered, with relevant clinical examples. The contribution of tumoral drug metabolism to cancer therapy can only be truly ascertained through large-scale prospective studies and supported by new technologies for tumor sampling and genetic analysis such as microarrays. Only then can efforts be concentrated in the design of better prodrugs or combination therapy to improve drug efficacy and individualize therapy.
Influence of water content of inspired air during and after exercise on induced bronchoconstriction
Authors: LP Boulet, H Turcotte
Journal: European Respiratory Journal (1991)

This study looked at the influence of inspired air water content on exercise-induced bronchospasm (EIB). On separate days, 12 mild asthmatics (4M, 8F), aged 18-39 yrs (mean: 27 yrs), performed four six minute steady-state exercises on ergometer at 80% of their maximum workload. Exercises were randomized to the following inspired air conditions: dry air (0% relative humidity (RH] during exercise followed by dry (DD) or humid air (100% RH) (DH) after exercise, humid air during exercise followed by dry (HD) or humid air (HH). Room temperature was kept constant (22 +/- 1 degree C) at all visits. Forced expiratory volume in one second (FEV1) was measured before and every 5 min for 25 min after exercise. Ventilation (VE) was not significantly different whether the exercise was done under dry or humid air. There was a residual bronchodilatation at the end of exercises performed in humid air, while at this time FEV1 was already lower than baseline when exercise was done in dry air conditions. The maximal fall in FEV1(%) following exercise was significantly greater after those performed in dry air: DD (29 +/- 5.6%) and DH (30 +/- 5.8%) than in humid air: HD (12 +/- 4.9%) and HH (20 +/- 4.9%) (p less than 0.05). The time-course of recovery from bronchoconstriction was significantly improved when inhaling dry air after exercise. However, the difference found in the maximal % fall in FEV1 after exercise when recovery was in dry compared to humid air did not achieve statistical significance. In conclusion, EIB is influenced by the changes in water content during and after exercise. Bronchoconstriction following exercise is minimal if exercise is done in humid air and recovery in dry air, and maximal if the exercise is performed in dry air and recovery in humid air.
Lipoprotein(a) and Coronary Heart Disease
Authors: John Danesh, Rory Collins, Richard Peto
Journal: Circulation (2000)

Background —Studies of the association between the plasma concentration of lipoprotein(a) [Lp(a)] and coronary heart disease (CHD) have reported apparently conflicting findings. We report a meta-analysis of the prospective studies with at least 1 year of follow-up published before 2000. Methods and Results —The following information was abstracted for each study: geographical location of study, size, type of cohort (population-based or selected because of previous disease), mean age, follow-up duration, blood storage temperature and duration, assay methods, degree of adjustment for potential confounders, and relationship of baseline Lp(a) measurement with subsequent CHD risk. There were 5436 deaths from CHD or nonfatal myocardial infarctions during a weighted mean follow-up of 10 years in the 27 eligible studies. Comparison of individuals in the top third of baseline plasma Lp(a) measurements with those in the bottom third in each study yielded a combined risk ratio of 1.6 (95% CI 1.4 to 1.8, 2 P &lt;0.00001), with similar findings when the analyses were restricted to the 18 studies of general populations (combined risk ratio 1.7, 95% CI 1.4 to 1.9; 2 P &lt;0.00001). Despite differences among studies in blood storage techniques and assay methods, there was no significant heterogeneity among the results from the 18 population-based studies or among those from the 9 studies of patients with previous disease. Lp(a) was only weakly correlated with classical vascular risk factors, and adjustment for those that had been recorded made little difference to the reported risk ratios. Conclusions —These prospective studies demonstrate a clear association between Lp(a) and CHD, but further studies are needed to determine the extent to which this is causal.
The new clinical trials on pharmacological treatment in pulmonary arterial hypertension
Authors: N. Galiè, A. Manes, A. Branzi
Journal: European Respiratory Journal (2002)

Past medical therapy for pulmonary arterial hypertension included the use of calcium-channel antagonists in acute vasoreactive subjects and oral anticoagulants and continuous intravenous administration of epoprostenol in the more severe cases. Recently, the thromboxane inhibitor terbogrel, the prostacyclin analogues treprostinil, beraprost and iloprost, and the endothelin receptor antagonist bosentan have been tested in clinical trials in &gt;1,100 patients. Except for terbogrel, all compounds improved the mean exercise capacity by different degrees, as assessed by the 6-min walk test. In the evaluation of the clinical relevance of exercise capacity improvements, additional elements need to be considered, such as baseline functional class and concomitant favourable effects on combined clinical events (including hospitalisations, mortality and rescue therapies), quality of life and haemodynamics. No trials have shown effects on mortality, as the study protocols were not designed for assessing this end-point. Each new compound presents side-effects that are unpredictable in the individual patient and require appropriate attention upon treatment initiation and maintenance. These new therapeutic options will be available in the near future and will allow tailoring of the most appropriate treatment to the single patient, according to an individualised benefit-to-risk ratio.
C-Reactive Protein, Insulin Resistance, and Metabolic Syndrome in a Population With a High Burden of Subclinical Infection
Authors: Barbara V. Howard, Lyle Best, Anthony Comuzzie, Sven O. E. Ebbesson, Stephen E. Epstein, Richard R. Fabsitz, Wm. James Howard, Angela Silverman, Hong Wang, Jianhui Zhu, Jason Umans
Journal: Diabetes Care (2008)

To explore relationships between C-reactive protein (CRP), subclinical infection, insulin resistance, and metabolic syndrome.Data from 1,174 Eskimos, aged >/=18 years, from the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study were analyzed; 40 participants with diabetes were eliminated. Baseline assessment included interviews, physical exam, and blood and urine sampling. Metabolic syndrome was assessed using Adult Treatment Panel III criteria. CRP and antibodies to common pathogens were measured.Although CRP was related in univariate analyses to insulin resistance and metabolic syndrome, relations were attenuated or eliminated after adjustment for relevant covariates. CRP was not higher among those with impaired fasting glucose (IFG), and pathogen burden was not related to insulin resistance, metabolic syndrome, or IFG.Pathogen burden and inflammation do not seem to be related to insulin resistance, metabolic syndrome, or IFG in this population. The inflammatory process may reflect insulin resistance or its correlates but most likely is not causative.
Forecasting the Future of Cardiovascular Disease in the United States
Authors: Paul A. Heidenreich, Justin G. Trogdon, Olga A. Khavjou, Javed Butler, Kathleen Dracup, Michael D. Ezekowitz, Eric Andrew Finkelstein, Yuling Hong, S. Claiborne Johnston, Amit Khera, Donald M. Lloyd-Jones, Sue A. Nelson, Graham Nichol, Diane Orenstein, Peter W.F. Wilson, Y. Joseph Woo
Journal: Circulation (2011)

Cardiovascular disease (CVD) is the leading cause of death in the United States and is responsible for 17% of national health expenditures. As the population ages, these costs are expected to increase substantially.To prepare for future cardiovascular care needs, the American Heart Association developed methodology to project future costs of care for hypertension, coronary heart disease, heart failure, stroke, and all other CVD from 2010 to 2030. This methodology avoided double counting of costs for patients with multiple cardiovascular conditions. By 2030, 40.5% of the US population is projected to have some form of CVD. Between 2010 and 2030, real (2008$) total direct medical costs of CVD are projected to triple, from $273 billion to $818 billion. Real indirect costs (due to lost productivity) for all CVD are estimated to increase from $172 billion in 2010 to $276 billion in 2030, an increase of 61%.These findings indicate CVD prevalence and costs are projected to increase substantially. Effective prevention strategies are needed if we are to limit the growing burden of CVD.
Tracheomalacia in children with reccurent low respiratory diseases
Authors: Lidija Petrushevska-Kolekjevska, Iskra Lazarevska, Jane Buzarov, Katerina Boshkovska, Slavica Kostadinova
Journal: European Respiratory Journal (2014)

Congenital airway malacia is one of the causes of irreversibile airways obstruction in children.The incidence in general population is unknown.If it is often diagnosed later in children and it is mixed with asthma.  Aim:To performe flexible bronchoscopy as a diagnstic procedure in repeated and prolonged wheezing in children.  Methods:We analyzed all flexible bronchoscopies performed at our department from 2007 to 2013.We summarized clinical features (wheezing,cought,reccurent pneumonia) of children with primary airmalacia estimated the predictive value of a clinical diagnosis by pediatritions.Results:In a total of 109 performed bronchoscopies airway malacia was diagnosed in 25 children(22,94%).The mean age was 4,2years(range 0-17).We find tracheomacia in 17 children,bronchomalacia of the right main bronchi in 12 children and 6 children have bronchomalacia of the left bronchi.In 53% of the airway malacia diagnosis the diagnose was not suspected prior to bronchoscopy.Presenting clinical signs of children with airway malacia were variable and atipical and similar with features of allergic asthma.  Conclusion:Primary airway malacia is not rare condition.It is difficult to recognize the malacia based on clinical features but we have to think of it performing bronchoscopy in children with reccurent lower respiratory infections and therapy resistant asthma.
Longitudinal change of prebronchodilator spirometric obstruction
Authors: F. A. A. M. Hoesein, P. Zanen, J.-W. J. Lammers
Journal: Thorax (2010)

RSV bronchiolitis was therefore 3.5e4.1-foldcompared with the population.Lung function by forced expiratory volume in 1 s (FEV 1 ), ratio of FEV 1 to forced vital capacity (FVC) and mid forced expiratory flow (FEF 25e75 ) was reduced in the former patients with RSV bronchiolitis with and without current asthma but not in asthmatic controls. 1The differences were significant in both pre-and post-bronchodilator measurements, suggesting the permanence of the changes.Instead, no evidence was found for permanent small airway dysfunction by lung clearance calculation. 1 In our study, 100 infants aged <24 months were hospitalised with bronchiolitis in 1992e3.Eighty-one attended the control visit at age 12 years; asthma was present in 20% of former patients with RSV and in 52% of former non-RSV patients (OR 0.27, 95% CI 0.09 to 0.82), and in 58% of former patients with rhinovirus and in 34% of former nonrhinovirus patients (OR 2.6, 95% CI 0.89 to 7.94). 3RSV bronchiolitis was associated with a restrictive pattern of lung function documented by reduced FVC. 4 A post-questionnaire study including population-based controls was performed in 2008 when the study subjects were 17e18 years of age (unpublished).Sixtyseven former patients with bronchiolitis and 155 controls attended, and current asthma was present in 30% and 5%, respectively (OR 7.9, 95% CI 3.3 to 19.3).Asthma was present in 25% of the former patients with RSV and in 26% of the former patients with rhinovirus.As in the study of Sigurs et al, 1 asthma was common after early life bronchiolitis but a viral aetiology of bronchiolitis no longer had a predictive value.Sigurs et al enrolled only RSV-positive patients with bronchiolitis aged <12 months treated in hospital, and >90% of the cases were aged #6 months. 1 In the Tucson birth cohort study from which our current concept about childhood wheezing phenotypes originates, patients with bronchiolitis were aged <24 months with parent-reported wheezing treated usually at home. 5 In the Finnish post-bronchiolitis studies highlighting the role of rhinovirus aetiology, RSV predominated in infants aged <6 months ('European bronchiolitis') and rhinovirus in those aged 6e24 months ('American bronchiolitis'). 3 4 In future studies of bronchiolitis, stratified analyses by age and viral findings are mandatory.
Wrist actigraphic assessment of sleep in 116 community based subjects suspected of obstructive sleep apnoea syndrome.
Authors: H A Middelkoop, A Knuistingh Neven, J J van Hilten, C W Ruwhof, H A Kamphuisen
Journal: Thorax (1995)

BACKGROUND--The combined use of wrist actigraphic assessment and self assessment of sleep in the screening of obstructive sleep apnoea syndrome was evaluated in a community based sample. METHODS--One hundred and sixteen community based subjects clinically suspected of having obstructive sleep apnoea (syndrome) were evaluated by means of simultaneous ambulatory recording of respiration (oronasal flow thermistry), motor activity (wrist actigraphy), and subjective sleep (sleep log) during one night of sleep. RESULTS--The subjects were distributed according to their apnoea index (AI); AI &lt; 1 (non-apnoeic snorers) 44%; AI 1- &lt; 5 39%; and AI &gt; or = 5 17%. High apnoea index values were associated with self reported disturbed sleep initiation and more fragmented and increased levels of motor activity and decreased duration of immobility periods, particularly in those with an apnoea index of &gt; or = 5. Across subjects the duration of immobility periods was the only predictor of the apnoea index, explaining 11% of its variance. Use of the multiple regression equation to discriminate retrospectively between those with an apnoea index of &lt; 1 and &gt; or = 5 resulted in sensitivity and specificity values of 75% and 43%, and 5% and 100%, respectively. CONCLUSIONS--The combined use of a sleep log and actigraphic assessment of sleep failed to identify reliably those subjects who suffered from obstructive sleep apnoea (syndrome) in a sample of community based subjects reporting habitual snoring combined with excessive daytime sleepiness and/or nocturnal respiratory arrests.
PTH-084 Nutritional Impact Of Anti-viral Therapy Of Genotype 1 Hepatitis C Patients
Authors: J Bennett, K Young, P Dundas, S English, L Mcleman, B Vijayan, A Fraser, A Mukhopadhya
Journal: Gut (2014)

<h3>Introduction</h3> Hepatitis C Virus (HCV) is a leading cause of chronic hepatitis and liver cirrhosis, with an estimated 170 million patients infected worldwide. The, UKmost common genotype of HCV is Genotype 1. For many years, the ‘Standard of Care’ has been prolonged therapy with the combination of Polyethylene glycol interferon-α and Ribavirin for one year. The recent approval of drugs such as Telaprevir and Boceprevir has restructured treatment for genotype 1 HCV infection, both for previously treated or treatment-naïve patients. Specific dietary intake is warranted for adequate absorption of the protease inhibitors and this has led to a structured dietary advice being given to patients. We wanted to compare the nutritional impact of antiviral therapy in two groups of patients who underwent either dual or triple therapy. <h3>Methods</h3> Treatment of hepatitis C patients at Aberdeen Royal Infirmary is undertaken by Hepatology specialist nurses who review these patients at designated time intervals. At each of these clinic visits the MUST score (Malnutrition Universal Screening Tool) is recorded in addition to the weight and BMI of the patient. Any patient who has a MUST score of 2 is referred for specialist dietetic input, which is also available at the clinic. At 4 weekly intervals, the HAD score for anxiety and depression is also recorded for all patients. <h3>Results</h3> A total of 73 patients with Genotype 1 underwent therapy in the year 2012–2013, including 25 patients with dual therapy of PEG-IFN and Ribavirin and 48 patients on triple therapy of PEG-IFN, Ribavirin and Telaprevir. There was no statistical difference in the initial weight, BMI and MUST scores of these two groups of patients. The mean weight fell from 89.6 ± 17.9 kg to 83.7 ± 15.6 kg by the end of treatment in the dual therapy group with a parallel fall in BMI from 30.7 ± 5.4 to 28.8 ± 4.6 kg/m<sup>2</sup>. However, in the triple therapy group, the mean weight increased from 82.2 ± 30.5 kg to 82.7 ± 26.0 kg and a stable BMI from 26.4 ± 9.5 to 26.2 ± 8.3 kg/m<sup>2</sup>. Dietary referral and intervention was needed in 7/25 patients on dual therapy (28%) as opposed to 7/48 patients on triple therapy (14.6%) (p = 0.23) <h3>Conclusion</h3> Weight reduction is a significant problem in patients undergoing dual therapy for hepatitis C as opposed to those undergoing triple therapy. Referral to the dietician was needed in a larger proportion of cases undergoing standard of care though it did not reach statistical significance. Dietary advice given with respect to protease inhibitors may have had a significant effect in combating the ill effects of the standard treatment of patients with Genotype 1 HCV infection. This specific advice should be extrapolated to all patients undergoing anti-viral treatment. <h3>Disclosure of Interest</h3> None Declared.
Clinical and pharmacological phase I evaluation of Exherin™ (ADH-1), a selective anti-N-cadherin peptide in patients with N-cadherin-expressing solid tumours
Authors: A. Perotti, C. Sessa, A. Mancuso, C. Noberasco, S. Cresta, A. Locatelli, M.L. Carcangiu, K. Passera, A. Braghetti, D. Scaramuzza, F. Zanaboni, A. Fasolo, G. Capri, M. Miani, W.P. Peters, L. Gianni
Journal: Annals of Oncology (2009)
PGD2-CRTH2 Pathway Promotes Tubulointerstitial Fibrosis
Authors: Hideyuki Ito, Xiaoxiang Yan, Nanae Nagata, Kosuke Aritake, Yoshinori Katsumata, Tomohiro Matsuhashi, Masataka Nakamura, Hiroyuki Hirai, Yoshihiro Urade, Koichiro Asano, Masato Kubo, Yasunori Utsunomiya, Tatsuo Hosoya, Keiichi Fukuda, Motoaki Sano
Journal: Journal of the American Society of Nephrology (2012)

Urinary excretion of lipocalin-type PGD(2) synthase (L-PGDS), which converts PG H(2) to PGD(2), increases in early diabetic nephropathy. In addition, L-PGDS expression in the tubular epithelium increases in adriamycin-induced nephropathy, suggesting that locally produced L-PGDS may promote the development of CKD. In this study, we found that L-PGDS-derived PGD(2) contributes to the progression of renal fibrosis via CRTH2-mediated activation of Th2 lymphocytes. In a mouse model, the tubular epithelium synthesized L-PGDS de novo after unilateral ureteral obstruction (UUO). L-PGDS-knockout mice and CRTH2-knockout mice both exhibited less renal fibrosis, reduced infiltration of Th2 lymphocytes into the cortex, and decreased production of the Th2 cytokines IL-4 and IL-13. Furthermore, oral administration of a CRTH2 antagonist, beginning 3 days after UUO, suppressed the progression of renal fibrosis. Ablation of IL-4 and IL-13 also ameliorated renal fibrosis in the UUO kidney. Taken together, these data suggest that blocking the activation of CRTH2 by PGD(2) might be a strategy to slow the progression of renal fibrosis in CKD.