tbuckley/cabot-search huggingface dataset:
Anaphylactic Shock after Insect-Sting Challenge in 138 Persons with a Previous Insect-Sting Reaction
Authors: Peter-Willem G. van der Linden
Journal: Annals of Internal Medicine (1993)

Objective: To study the rate and severity of anaphylactic reaction in relation to plasma levels of cardiovascular mediators in persons with a history of insect-sting anaphylactic shock who were rechallenged with a sting by the same insect. Design: A cohort study with measurements before and after intentional sting challenge. Setting: Intensive care unit of an 830-bed general hospital, a national center of insect-sting anaphylaxis in The Netherlands. Patients: A total of 138 patients referred after a previous anaphylactic reaction to a Hymenoptera sting; and 8 volunteers. Measurements: Signs of anaphylaxis and plasma levels of catecholamines and angiotensins. Main Results: Only 39 of 138 (28%) of patients with a previous insect-sting anaphylactic reaction developed anaphylactic symptoms after sting challenge. Values of cardiovascular mediators and mean arterial pressure did not differ after the challenge from initial values in the volunteers or in the patients with a mild or no reaction after challenge. In the 17 patients with anaphylactic shock, mean arterial pressure decreased from 97 ± 11 (mean ±SD) to 65 ± 17 mm Hg (P < 0.001), epinephrine levels rose from a median of 0.3 nmol/L (range, 0.2 to 2.3 nmol/L) to 2.5 nmol/L (0.2 to 35.7 nmol/L; P < 0.05), norepinephrine from 1.5 nmol/L (0.5 to 6.7) to 5.9 nmol/L (1.6 to 30.9 nmol/L; P < 0.01), and angiotensin II from 61 pmol/L (7 to 217 pmol/L) to 105 pmol/L (11 to 286 pmol/L; P < 0.01), all within 5 minutes after the onset of anaphylactic symptoms. The rise of these mediators correlated with the drop in blood pressure (P < 0.001). Dopamine and angiotensin I levels did not change in any participants. Conclusions: A recurrent insect-sting anaphylactic reaction occurred in only 28% of patients with a previous reaction. During this recurrent reaction, plasma levels of endogenous epinephrine, norepinephrine, and angiotensin II rose in relation to hypotension.
Abstract 13003: Efficacy of Cilostazol on Platelet Reactivity and Cardiovascular Outcomes in Patients Undergoing Percutaneous Coronary Intervention: Insights From a Meta-Analysis of Randomized Trials
Authors: Bora Toklu, Amita Singh, Frederick Feit, Sripal Bangalore
Journal: Circulation (2014)

Introduction: Cilostazol overcomes high on-treatment platelet reactivity (HTPR) and reduce adverse cardiovascular (CV) outcomes after percutaneous coronary intervention (PCI). However, the role for triple antiplatelet therapy (TAPT) with cilostazol in addition to aspirin and clopidogrel after PCI is not well defined. Methods: We conducted a MEDLINE/EMBASE/CENTRAL search for randomized trials, until May 2014, evaluating TAPT compared with dual antiplatelet therapy (DAPT) of aspirin and clopidogrel alone in patients undergoing PCI and reporting platelet reactivity and/or CV outcomes. The primary platelet reactivity outcome was differences in platelet reactivity unit (PRU) with secondary outcomes of %platelet inhibition and rate of HTPR. The primary CV outcome was major adverse cardiovascular events (MACE), with secondary outcomes of death, cardiovascular death, myocardial infarction (MI), stent thrombosis (ST), target lesion revascularization (TLR), and target vessel revascularization (TVR) as well as safety outcomes of bleeding and drug discontinuations. Results: In 17 trials that evaluated platelet reactivity outcomes, the mean PRU value was 47.73units lower with TAPT vs. DAPT (95% CI -61.41 to -34.04, P &lt;0.0001; mean PRU 182.90 vs. 232.65). TAPT also reduced platelet inhibition by 12.71% (95% CI 10.76-14.67, P &lt;0.0001), and led to a 60% reduction in the risk of HTPR (RR=0.40; 95% CI 0.30-0.53) compared with DAPT. Moreover, among the 34 trials that evaluated CV outcomes, TAPT reduced the risk of MACE (IRR=0.68; 95% CI 0.60-0.78), TLR (IRR=0.57; 95% CI 0.44-0.73), TVR (IRR=0.69; 95% CI 0.59-0.81) and stent thrombosis (IRR=0.63; 95% CI 0.40-0.98) with no difference for other outcomes including bleeding, even in trials using drug eluting stents. Drug discontinuation due to adverse effects was however higher with TAPT vs. DAPT (IRR=1.59; 95% CI 1.32-1.91). Conclusions: In patients undergoing PCI, addition of cilostazol to dual antiplatelet therapy results in decreased platelet reactivity and a significant reduction in CV outcomes including stent thrombosis, even in the drug eluting stent era.
Fibrinogen, t-PA, and PAI-1 plasma levels in patients with pulmonary hypertension.
Authors: K Huber, R Beckmann, H Frank, M Kneussl, J Mlczoch, B R Binder
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

We measured fibrinogen levels as well as the fibrinolytic parameters tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) in plasma samples obtained at basal conditions and after stimulating the fibrinolytic system by venous occlusion (VO). Samples were taken from patients with primary pulmonary hypertension (PPH), with secondary thromboembolic pulmonary hypertension (SPHTH), with secondary pulmonary hypertension due to congenital heart disease with Eisenmenger's reaction (SPHCD), and from healthy control individuals (CON). Fibrinogen levels were not significantly different between the groups with PPH and SPHTH or between SPHCD and CON. The latter groups, however, exhibited significantly lower fibrinogen plasma levels compared with PPH or SPHTH (p < 0.01). Basal plasma levels of t-PA antigen, t-PA activity, and PAI-1 activity, respectively, did not differ significantly between the study groups. After VO, mean t-PA activity levels increased to a higher extent in control subjects compared with patients with PPH, or SPHTH, or SPHCD, with significant differences only between CON and SPHTH or CON and PPH (p < 0.03). Patients with PPH and SPHTH exhibit both increased fibrinogen plasma levels and a diminished fibrinolytic response compared with healthy subjects. Moreover, the fibrinogen plasma levels in patients with SPHCD are in normal range, and the fibrinolytic response is similar to CON compared with PPH and SPHTH, thus indicating the existence of a comparable prothrombotic situation in patients with PPH and SPHTH.
Twelve-monthly versus six-monthly radiological screening for active case-finding of tuberculosis: a randomised controlled trial
Authors: G. J. Churchyard, K. Fielding, S. Roux, E. L. Corbett, R. E. Chaisson, K. M. De Cock, R. J. Hayes, A. D. Grant
Journal: Thorax (2010)

<h3>Background</h3> The incidence of tuberculosis has increased among South African gold miners despite comprehensive control programmes, including a radiological screening programme. No data are available as to the optimal frequency of screening. The aim of this study was to compare 6-monthly and 12-monthly radiological screening for active tuberculosis case-finding. <h3>Methods</h3> Employees of a gold mining company were randomly assigned to the control arm (screening at baseline, 12 and 24 months) or the intervention arm (additional 'intervention' radiographs at 6 and 18 months after baseline). Study outcomes included proportion of tuberculosis cases detected by screening, proportion smear-positive, extent of disease and mortality. <h3>Results</h3> 22 634 miners were randomised. Compared with 12-monthly screening, 6-monthly screening detected more tuberculosis suspects but not more cases, partly due to greater attrition between screening and further investigation after 'intervention' compared with routine radiographs. Tuberculosis cases detected in the 6-monthly versus the 12-monthly screening arm had less extensive disease (p=0.05) and a lower tuberculosis-specific mortality (death on tuberculosis treatment) (2.1 and 2.8 per 1000 person-years respectively, HR 0.73, 95% CI 0.50 to 1.08, p=0.1), which was most marked in the first 2 months of treatment (HR 0.48, 95% CI 0.23 to 0.98, p=0.04) when death from tuberculosis is most likely. <h3>Discussion</h3> In settings with a high prevalence of HIV and tuberculosis despite standard tuberculosis control measures, more frequent case-finding may reduce the extent of disease, tuberculosis mortality and tuberculosis transmission through earlier detection of active tuberculosis cases. To be effective, however, all tuberculosis suspects identified through screening must be investigated for tuberculosis.
Incidence of Metachronous Testicular Cancer in Patients With Extragonadal Germ Cell Tumors
Authors: J. T. Hartmann, S. D. Fossa, C. R. Nichols, J.-P. Droz, A. Horwich, A. Gerl, J. Beyer, J. Pont, K. Fizazi, H. Hecker, L. Kanz, L. Einhorn, C. Bokemeyer
Journal: JNCI Journal of the National Cancer Institute (2001)

The frequency of subsequent testicular cancer (referred to as metachronous testicular cancer) in men who have had previous testicular cancer is relatively high. The rate of metachronous testicular cancer in men with extragonadal germ cell tumors (EGCTs), however, is largely unknown. We conducted a retrospective study of EGCT patients to determine the incidence, cumulative risk, and specific risk factors for metachronous testicular cancers.A standardized questionnaire about patient characteristics, the extent of EGCT disease, any second malignancies, and treatments received was completed for 635 patients with EGCTs identified from the medical records of 11 cancer centers in Europe and the United States from 1975 through 1996. Comparisons with age group-specific data from the Saarland, Germany, population-based cancer registry were used to calculate the standardized incidence ratio (SIR). The Kaplan-Meier method was used to analyze survival data and cumulative risk. All statistical tests were two-sided.Sixteen EGCT patients (4.1%) developed metachronous testicular cancers, with a median time between diagnoses of 60 months (range, 14-102 months). The risk of developing metachronous testicular cancers was statistically significantly increased in patients with EGCTs (observed = 16; expected = 0.26; SIR = 62; 95% confidence interval [CI] = 36 to 99) and in subsets of EGCT patients with mediastinal location (SIR = 31; 95% CI = 8 to 59), retroperitoneal location (SIR = 100; 95% CI = 54 to 172), and nonseminomatous histology (SIR = 75; 95% CI = 43 to 123). The cumulative risk of developing a metachronous testicular cancer 10 years after a diagnosis of EGCT was 10.3% (95% CI = 4.9% to 15.6%) and was higher among patients with nonseminomatous EGCTs (14.3%; 95% CI = 6.7% to 21.9%) and retroperitoneal EGCTs (14.2%; 95% CI = 5.6% to 22.8%) than among patients with seminomatous EGCTs (1.4%; 95% CI = 0.0% to 4.2%) and mediastinal EGCTs (6.2%; 95% CI = 0.1% to 12.2%).Patients with EGCTs, particularly those with retroperitoneal or nonseminomatous tumors, but also those with primary mediastinal EGCTs, are at an increased risk of metachronous testicular cancer.
Randomized, Multinational, Phase III Study of Docetaxel Plus Platinum Combinations Versus Vinorelbine Plus Cisplatin for Advanced Non–Small-Cell Lung Cancer: The TAX 326 Study Group
Authors: Frank Fossella, Jose R. Pereira, Joachim von Pawel, Anna Pluzanska, Vera Gorbounova, Eckhard Kaukel, Karin V. Mattson, Rodryg Ramlau, Aleksandra Szczęsna, Panagiotis Fidias, Michael Millward, Chandra P. Belani
Journal: Journal of Clinical Oncology (2003)

To investigate whether docetaxel plus platinum regimens improve survival and affect quality of life (QoL) in advanced non-small-cell lung cancer (NSCLC) compared with vinorelbine plus cisplatin as first-line chemotherapy.Patients (n = 1,218) with stage IIIB to IV NSCLC were randomly assigned to receive docetaxel 75 mg/m2 and cisplatin 75 mg/m2 every 3 weeks (DC); docetaxel 75 mg/m2 and carboplatin area under the curve of 6 mg/mL * min every 3 weeks (DCb); or vinorelbine 25 mg/m2/wk and cisplatin 100 mg/m2 every 4 weeks (VC).Patients treated with DC had a median survival of 11.3 v 10.1 months for VC-treated patients (P =.044; hazard ratio, 1.183 [97.2% confidence interval, 0.989 to 1.416]). The 2-year survival rate was 21% for DC-treated patients and 14% for VC-treated patients. Overall response rate was 31.6% for DC-treated patients v 24.5% for VC-treated patients (P =.029). Median survival (9.4 v 9.9 months [for VC]; P =.657; hazard ratio, 1.048 [97.2 confidence interval, 0.877 to 1.253]) and response (23.9%) with DCb were similar to those results for VC. Neutropenia, thrombocytopenia, infection, and febrile neutropenia were similar with all three regimens. Grade 3 to 4 anemia, nausea, and vomiting were more common (P <.01) with VC than with DC or DCb. Patients treated with either docetaxel regimen had consistently improved QoL compared with VC-treated patients, who experienced deterioration in QoL.DC resulted in a more favorable overall response and survival rate than VC. Both DC and DCb were better tolerated and provided patients with consistently improved QoL compared with VC. These findings demonstrate that a docetaxel plus platinum combination is an effective treatment option with a favorable therapeutic index for first-line treatment of advanced or metastatic NSCLC.
The role of reference values in interpreting lung function tests
Authors: R.O. Crapo
Journal: European Respiratory Journal (2004)

Advances in genomic medicine have lead to debate about the potential inclusion of genetic tests for susceptibility to common complex disorders in newborn screening programmes. Empirical evidence concerning psychosocial reactions to genetic testing is a crucial component of both ethical debate and policy development, but while there has been much speculation concerning the possible psychosocial impact of screening newborns for genetic susceptibilities, there remains a paucity of data. The aim of the study reported here is to provide some of this missing empirical evidence, using type 1 diabetes as an example of a common disorder with multiple significant genetic contributors to its aetiology. Semi-structured interviews were conducted with 11 parents of babies who had received increased risk results in a study that involved newborn screening for genetic susceptibility to type 1 diabetes. Interpretative phenomenological analysis was used to evaluate the data. The interview data suggest that the probabilistic nature of results of genetic susceptibility tests impacts upon all aspects of parents9 psychosocial reactions, resulting in a complex and dynamic process quite different to that described in relation to current newborn screening programmes. While parents generally reported fairly minor levels of concern in response to news of their child9s increased genetic risk, these worries frequently recurred, and perception of risk also varied and fluctuated over time. Both individual and contextual factors appeared to interact with the inherent uncertainty of the test result to contribute to the dynamic nature of parental reactions, and their behavioural responses. The implications of these findings for future research and for the debate concerning potential expansion of newborn screening are discussed.
Association of Tumor Angiogenesis With Bone Marrow Micrometastases in Breast Cancer Patients
Authors: S. B. Fox, K. C. Gatter, R. D. Leek, A. L. Harris, J. Bliss, J. L. Mansi, B. Gusterson
Journal: JNCI Journal of the National Cancer Institute (1997)

Background and Purpose: The microscopic detection of tumor cells (micrometastases) in bone marrow and the extent of blood vessel formation (angiogenesis) in primary tumor specimens are recognized as independent prognostic markers in patients with breast cancer. Since micrometastases occur as a consequence of interaction between the neoplastic cells and the tumor neovasculature, we have examined the relationship between these markers to determine whether the degree of angiogenesis is related to the presence of micrometastases. Methods: Micrometastases were identified in bone marrow aspirates collected from multiple sites in 214 breast cancer patients prior to surgery (mastectomy or lumpectomy). Tumor cells were detected through an examination of epithelial membrane antigen expression and an analysis of cell morphology. Tumor vascularity was graded semiquantitatively or quantitatively (Chalkley point count) after immunohistochemical staining of the CD31 antigen expressed by the endothelial cells. The reproducibility and accuracy of the vascular grading were validated by use of kappa statistics. Associations between micrometastases and clinicopathologic characteristics, including angiogenesis, were examined using chi-squared and logistic regression techniques. All tests of statistical significance were twosided. Results: Of the 214 patients, 42 (20%) were positive for bone marrow micrometastases and 75 (35%) had tumors of high vascular grade. There was 86% agreement between vascular grades assessed twice for 35 tumors (kappa statistic = 0.66); for 22 evaluated tumors, there was absolute concordance between vascular grade and Chalkley point count. There were significant positive associations between tumor angiogenesis and micrometastasis ( P = .01), tumor grade ( P = .003), and estrogen receptor expression ( P = .007); however, no significant associations were observed with tumor size ( P = .9), lymph node status ( P = .33), vascular invasion (peritumoral blood or lymph vessels) ( P = .9), menopausal status ( P = .17), or age (P = .12). Adjusting for confounding factors, multivariate analysis showed that only tumor angiogenesis (odds ratio = 2.7; P P = .016) and vascular invasion (odds ratio = 2.7; P = .012) were significant determinants for the presence of micrometastases. Conclusions: This study suggests that an assessment of tumor angiogenesis and vascular invasion gives a reliable indication of the likelihood of the presence of bone marrow micrometastases in patients with breast cancer and that both processes contribute to metastases.
Efficacy of smoking cessation assistance in Tunisian women
Authors: Besma Ourari, Heifa Zaibi, Jihen Ben Amar, M. Ali Baccar, Saloua Azzabi, Eya Tangour, Mouna Berraies, Hichem Aouina, Leila El Gharbi, Hend Bouacha
Journal: European Respiratory Journal (2012)

Introduction:   Smoking is the most preventable cause of death. Although, woman started smoking in greater numbers later than man, she seems to have more difficulties in quitting cigarette than him.   Aim:    Evaluate the smoking intoxication rate in Tunisian woman and the effectiveness of smoking cessation intervention.   Patients and methods:   It9s a prospective study, including 100 women smokers treated for smoking cessation during the period from 2007 to 2010. We extracted data on smoking history, degree of nicotine dependence, strategies of smoking cessation and the most successful intervention after 3 and 6 months.   Results:   Mean age of women smokers was 43.6 +/- 13.3 years. The mean age of onset of tobacco use was 19.7 +/- 6.4 years. The mean duration of exposition was 23 +/- 12 years, with a mean of cigarettes consummation of 22 +/- 11 cigarettes /day. Tobacco dependence level was important in 65% of women. A half of them had a low level of education attained, and most of them (71.4%) had unfavourable socioeconomic status. According to HAD test, 20 patients were anxious and 45 patients were depressive. The principal reason of quitting cigarette smoking was health problems associated with cigarette (83.2%). Nicotine replacement treatment was the most strategy prescribed (98%). After the first counselling, 40% were lost of sight. Continuous cessation rate at 3 months was 65%. Only 15% stopped definitely smoking at 6 months. Relapses were especially due to greater withdrawal symptoms.   Conclusion:   This study illustrates the importance of tobacco dependence in Tunisian women. Smoking seems to become a phenomenon associated with poorer and less-educated people. Relapses were common after 6 months of smoking cessation assistance.
Combined Targeting of Endothelin A Receptor and Epidermal Growth Factor Receptor in Ovarian Cancer Shows Enhanced Antitumor Activity
Authors: Laura Rosanò, Valeriana Di Castro, Francesca Spinella, Giampaolo Tortora, Maria Rita Nicotra, Pier Giorgio Natali, Anna Bagnato
Journal: Cancer Research (2007)

Abstract Ovarian carcinomas overexpress endothelin A receptors (ETAR) and epidermal growth factor (EGF) receptor (EGFR). In these cells, endothelin-1 (ET-1) triggers mitogenic and invasive signaling pathways that are in part mediated by EGFR transactivation. Combined targeting of ETAR, by the specific ETAR antagonist ZD4054, and of EGFR by the EGFR inhibitor gefitinib (IRESSA), may offer improvements in ovarian carcinoma treatment. In HEY and OVCA 433 ovarian carcinoma cells, ET-1 or EGF induced rapid activation of EGFR, p42/44 mitogen-activated protein kinase (MAPK), and AKT. ZD4054 was able to reduce the ET-1–induced EGFR transactivation. Gefitinib significantly inhibited EGF- and ET-1–induced EGFR phosphorylation, but incompletely reduced the ET-1–induced activation of downstream targets. ZD4054 plus gefitinib resulted in a greater inhibition of EGFR, MAPK, and AKT phosphorylation, indicating the critical role of these interconnected signaling proteins. ZD4054 effectively inhibited cell proliferation, invasiveness, and vascular endothelial growth factor (VEGF) secretion. Concomitantly, ZD4054 enhanced apoptosis and E-cadherin promoter activity and expression. In both cell lines, the drug combination resulted in a significant decrease in cell proliferation (65%), invasion (52%), and VEGF production (50%), accompanied by a 2-fold increase in apoptosis. The coadministration of ZD4054 enhanced the efficacy of gefitinib leading to partial (82%) or complete tumor regression on HEY ovarian carcinoma xenografts. Antitumor effects were paralleled by biochemical and immunohistologic evidence of decreased vascularization, Ki-67, matrix metalloproteinase-2 (MMP-2), VEGF, MAPK and EGFR, and enhanced E-cadherin expression. The cross-signaling between the EGFR/ETAR pathways provides a rationale to combine EGFR inhibitors with ETAR antagonists, identifying new effective therapeutic opportunities for ovarian cancer. [Cancer Res 2007;67(13):6351–9]
Effect of breast feeding in infancy on blood pressure in later life: systematic review and meta-analysis
Authors: Christopher G Owen, Peter H Whincup, Julie A Gilg, Derek G Cook
Journal: BMJ (2003)

<h3>BACKGROUND/AIMS</h3> Although human ocular toxocariasis causes severe vision defect, little is known about its aetiology, diagnosis, and treatment. To develop a new animal model for human ocular toxocariasis, ophthalmological findings of fundi in Mongolian gerbils, <i>Meriones unguiculatus</i>, and BALB/c mice were investigated following infection with<i>Toxocara canis</i>. <h3>METHODS</h3> Using an ophthalmoscope, which was specifically developed to observe the fundi of small animals, ocular changes of fundi of 20 gerbils and 11 mice were monitored after oral infection with embryonated eggs of<i>T canis</i>. <h3>RESULTS</h3> Vitreous, choroidal, and retinal haemorrhages were consistently observed in Mongolian gerbils, but rarely in mice. Severe exudative lesions and vasculitis were often present in gerbils but not in mice. Migrating larvae were also frequently observed in gerbils. <h3>CONCLUSION</h3> Mongolian gerbils are more appropriate animal model for human ocular toxocariasis than previously used experimental animal such as mice, guinea pigs, rabbits, and monkeys because of its high susceptibility of ocular infection.