tbuckley/cabot-search huggingface dataset:
Immuno-allergic reactions to antituberculosis treatment
Authors: Sonia Habibech, Hajer Racil, Safa Hfaidh, Sana Cheikhrouhou, Naouel Chaouch, Abdellatif Chabbou
Journal: European Respiratory Journal (2013)

Introduction: 

Pulmonary Tuberculosis (PTB) is a major public health problem in Tunisia. Immunoallergic reactions (IAR) to antiTB treatment are rare. It is a real problem of management and may involve life-threatening.

Materials and methods: 

It is a retrospective study. Among 315 non HIV confirmed PTB patients (P) hospitalized in our department between 2001 and 2012, 19 P (6%) developed IAR to anti-TB treatment.

Results: 

It is 19 male P with an average age of 42 years (between 18 and 71 years). Five of them had in their history PTB correctly treated. Smoking was observed in 19 P. 17 P had sequential TB treatment. IAR reported in order of frequency are: cutaneous pruritus and or urticaria (9 cases), hematological (6 cases), renal failure (4 cases). The occurrence of these reactions was observed on average 17 day of the introduction of antiTB treatment.

Rifadine was incriminated in renal failure (3 cases), thrombocytopenia (2 cases), anemia (4 cases), leukoneutropenia (2 cases) and skin rash (1 case). Piazoline has been implicated in skin reactions (3 cases).

Five P stopped treatment because of adverse events and 1 death related to immune-allergic renal failure was noted. Five patients received symptomatic treatment without stopping TB drugs with a good clinical outcome. The average duration of treatment was 8 months. A delay of smear negativity was noted in 8 P and a relapse in 3. Resistance was confirmed by an antibiogram in 3P.

Conclusion: 

The occurrence of severe IAR is unpredictable. This is a real problem when this therapeutic side effect is caused by a major TB treatment. Careful monitoring of patients is necessary and reporting any side effects in the service of pharmacovigilance is needed in all cases.
Randomized phase II study evaluating veliparib (ABT-888) with temozolomide in patients with metastatic melanoma
Authors: M.R. Middleton, P. Friedlander, O. Hamid, A. Daud, R. Plummer, N. Falotico, B. Chyla, F. Jiang, E. McKeegan, N.M. Mostafa, M. Zhu, J. Qian, M. McKee, Y. Luo, V.L. Giranda, G.A. McArthur
Journal: Annals of Oncology (2015)
The impact of ozone
Authors: A. Munzer
Journal: Environmental Health Perspectives (1995)

Unlike the other four main air pollutants - carbon monoxide, sulfur dioxide, nitrogen dioxide, and particulates - for which the EPA has established National Ambient Air Quality Standards (NAAQS), ozone is not directly emitted into the air from automobiles, power plants, or industrial facilities. Instead, it is a photochemical pollutant, created when sunlight catalyzes chemical reactions with other pollutants. The main culprits in ozone formation, called ozone precursors, are nitrogen oxides, and volatile organic compounds, which stem from numerous activities. But controlling ozone precursors may not solve the ozone problem. Ozone control is complicated by the fact that the pollutant is transported across entire regions by wind, making it difficult for any individual area to control ozone within its boundaries. Given the regional nature of ozone pollution, it might be more appropriate for the EPA to identify regional nonattainment areas, rather than metropolitan areas, as is now the case. But expanding the areas of nonattainment, which is what would occur under this regional approach would be politically unpopular. Ultimately, the EPA administrator will face the unenviable task of setting the ozone standard, but science shoud not be expected to provide clear-cut answers to setting a specific standard.
Frequency and characteristics of circulating CD4<sup>+</sup> CD28<sup>null</sup> T cells in patients with psoriasis
Authors: X.T. Lima, M.L. Cintra, A.C. Piaza, R.L. Mamoni, R.T. Oliveira, R.F. Magalhães, M.H. Blotta
Journal: British Journal of Dermatology (2015)

Psoriasis is a chronic inflammatory disease that affects the skin. CD4+ CD28null cells are a subset of T lymphocytes associated with systemic inflammation and increased cardiovascular disease risk, and may be involved in the pathogenesis of psoriasis. To study the features of circulating CD4+ CD28null cells in patients with psoriasis, adjusted for the influence of known cardiovascular disease risk factors. Forty‐two patients with psoriasis and 42 controls entered the study. Peripheral blood mononuclear cells were analysed for the frequency of CD4+ CD28null T lymphocytes and their expression of cytotoxic granules and homing receptors. Immunostaining for cutaneous cytotoxic granules was assessed in skin biopsies from 11 patients. There were no differences in the frequency of CD4+ CD28null T cells between groups in all situations analysed. However, there was an increased number of cells expressing cytotoxic granules and a decreased number expressing CXCR3 in ex vivo samples of patients with psoriasis. A negative correlation was observed between the frequency of ex vivo CD4+ CD28null cells and psoriasis severity. After clinical remission in nine patients, ex vivo CD4+ CD28null lymphocytes expressing cytotoxic granules decreased. Perforin‐, granzyme B‐ and granulysin‐containing cells were found in skin lesions. Patients with psoriasis also had increased plasma levels of C‐reactive protein. These data suggest that cytotoxic cells, such as CD4+ CD28null lymphocytes, within an inflammatory environment may play a role in the pathogenesis of psoriasis.
Lung Clearance Index and Structural Lung Disease on Computed Tomography in Early Cystic Fibrosis
Authors: Kathryn A. Ramsey, Tim Rosenow, Lidija Turkovic, Billy Skoric, Georgia Banton, Anne-Marie Adams, Shannon J. Simpson, Conor Murray, Sarath C. Ranganathan, Stephen M. Stick, Graham L. Hall
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

The lung clearance index is a measure of ventilation distribution derived from the multiple-breath washout technique. It has been suggested as a surrogate for chest computed tomography to detect structural lung abnormalities in individuals with cystic fibrosis (CF); however, the associations between lung clearance index and early structural lung disease are unclear.We assessed the ability of the lung clearance index to reflect structural lung disease on the basis of chest computed tomography across the entire pediatric age range.Lung clearance index was assessed in 42 infants (ages 0-2 yr), 39 preschool children (ages 3-6 yr), and 38 school-age children (7-16 yr) with CF before chest computed tomography and in 72 healthy control subjects. Scans were evaluated for CF-related structural lung disease using the Perth-Rotterdam Annotated Grid Morphometric Analysis for Cystic Fibrosis quantitative outcome measure.In infants with CF, lung clearance index is insensitive to structural disease (κ = -0.03 [95% confidence interval, -0.05 to 0.16]). In preschool children with CF, lung clearance index correlates with total disease extent. In school-age children, lung clearance index correlates with extent of total disease, bronchiectasis, and air trapping. In preschool and school-age children, lung clearance index has a good positive predictive value (83-86%) but a poor negative predictive value (50-55%) to detect the presence of bronchiectasis.These data suggest that lung clearance index may be a useful surveillance tool to monitor structural lung disease in preschool and school-age children with CF. However, lung clearance index cannot replace chest computed tomography to screen for bronchiectasis in this population.
Maternal smoking during pregnancy and the risk of asthma related symptoms in the early childhood
Authors: Monica Alexandra Stoica, Andrei Dumitrescu, Maria Saftoiu
Journal: European Respiratory Journal (2011)

Maternal smoking during pregnancy and fetal growth retardation might adversely affect early lung development and increase the risks of asthma-related symptoms.

The study of the associations of maternal smoking during pregnancy and fetal growth, measured in different periods of pregnancy with asthma-related symptoms in early childhood.

Methods: We performed a 4 years (2006-2010) prospective population-based cohort study starting in pregnancy. Fetal growth retardation was defined as a decrease of 1 gestational age adjusted standard deviation score in weight from 3rd trimester to birth. Maternal smoking during pregnancy (I, II, III trimesters) and wheezing, lower respiratory tract infections (LRTI) and diagnosed asthma until the age of 3 years were assessed by questionnaires. Adjusted logistic regression analyses were performed in 1217 subjects.

Results: Maternal first trimester only smoking was not associated with asthma-related symptoms in the children. Continued maternal smoking during pregnancy was associated with wheezing at 1, 2 and 3 years with adjusted odds ratios (aOR) 1.47 (94% confidence interval 1.14 to 19.4), 1.51 (1.13, 2.10) and 1.60 (1.09, 2.37), and with LRTI at 2 years (aOR 1.69 (1.19, 2.41)) but not with diagnosed asthma. Fetal growth retardation was not associated with any asthma-related symptoms. Children of continued smoking mothers with fetal growth retardation had higher risks of wheezing than children of smoking mothers without fetal growth retardation.

Conclusions: Continued maternal smoking during pregnancy is associated with increased risks of wheezing in early childhood. These associations are stronger in children with fetal growth retardation.
The prognostic value of CK20, 34betaE12, p53, bcl2, c-erbB-2, Ki-67, CD44 and PSMA immunohistochemical expression in urothelial urinary bladder carcinoma
Authors: C. D. Petraki, M. M. Vaslamatzis, K. Dimosthenous, N. D. Alevizopoulos, K. D. Petraki, G. Kanelis, P. A. Papanastasiou, I. Evangelou, P. Stassinopoulou, A. K. Grigorakis
Journal: Journal of Clinical Oncology (2005)

4588 Background: To study the prognostic value of the immunohistochemical expression of cytokeratin 20 (CK20), 34betaE12 antigen, p53, bcl2 & c-erbB-2 oncoproteins, the cell proliferation marker Ki-67, the cell adhesion molecule CD44 and the prostate- specific membrane antigen (PSMA), in predicting tumor relapse in patients (pts) with primary low-stage (pTa/T1) urothelial urinary bladder carcinoma (UUBC). Methods: Included in the study were 174 consecutive pts, median age 62 (18–75) years who underwent transurethral resection (TUR) of a UUBC between 3/2003 and 11/2004. Hundred-thirty-two/174 (76%) pts had a low-stage UUBC (pTa: 36/132 & T1: 96 pts) and underwent no further treatment. Their median follow-up period was 11.5 (3–20) months and 46/132 (35%) pts recurred. All tumors were graded in accordance with the 1998 WHO/ISUP and 1999 WHO classifications. The immunohistochemical method of streptavidin-biotin-peroxidase was performed. Results: CK20, p53, c-erbB-2, Ki-67, CD44 and PSMA showed a statistically significant positive relation with histological grade (HG) and pathological stage respectively (p=0.003, 0.000, 0.004, 0.000, 0.023, 0.009 and 0.000, 0.000, 0.041, 0.000, 0.006, 0.002 respectively) and bcl2 only with HG (p=0.032). The recurrence rate of the pTa/T1 subgroup was positively related with HG, pathological substaging (pT1a/T1b), CK20, bcl2 and Ki-67 (p=0.000, 0.000, 0.000, 0.017 and 0.000 respectively). Kaplan-Meier survival curves showed that HG, pathological substaging, CK20, bcl2, c-erbB-2 and Ki-67 had a positive statistically significant relation with the recurrence-free interval (p=0.0000, 0.0012, 0.0000, 0.0121, 0.0180 and 0.0000 respectively). However multivariate analysis showed that HG, Ki-67 and PSMA were independent unfavorable predictors for recurrence (p=0.011, 0.008 and 0.020 respectively). Conclusions: Ki-67 and PSMA may be useful markers for recurrence prediction & decision management in pts with primary pTa/T1 UUBC after TUR. No significant financial relationships to disclose.
High-dose vitamin D supplementation and liver histology in NASH: Table 1
Authors: Matthew T Kitson, Alan Pham, Adam Gordon, William Kemp, Stuart K Roberts
Journal: Gut (2015)

Dear Editor,

We read with great interest the recent study by Beilfuss et al ,1 which found vitamin D supplementation to ameliorate transforming growth factor-β-induced fibrogenesis in human hepatic stellate cells.

Vitamin D is an important secosteroid hormone with pleiotropic effects that extend well beyond its established regulatory role in calcium and bone homeostasis. These include its recently described involvement in the regulation of immunomodulation, cell proliferation and differentiation, as well as anti-inflammatory and anti-fibrotic properties.2 Subjects with non-alcoholic fatty liver disease (NAFLD) have a lower 25-hydroxyvitamin D [25(OH)D] level,3 which is …
Yield of pleural cytology and macroscopic pleural invasion in metastatic pleural effusion
Authors: Jérôme Plojoux, Marios Froudarakis, Elise Kaspi, Sophie Laroumagne, Hervé Dutau, Philippe Astoul
Journal: European Respiratory Journal (2014)

Introduction : Diagnostic sensitivity of pleural fluid (PF) cytology is 40-60% and is related to sample size and cytologist's experience. Pleural extension could be a factor. We assessed PF cytology yield in relation to pleural invasion.

Method : Medical records of 288 patients were reviewed. PF cytology, reported appearance during thoracoscopy and malignant diagnosis were inclusion criteria. Mesothelioma was excluded.

Results : NSCLC and breast cancer were most frequent etiologies

View this table:

Final diagnosis





. 56% of patients had positive PF cytology. Thoracoscopy reported parietal pleural invasion in 97% of subjects. 81% of patients with positive cytology had visceral pleural invasion, while only 30% of those with negative cytology

![Figure][1] 



.

Conclusion : PF cytological yield is significantly higher in patients with visceral pleural invasion. Positive PF cytology might be associated with more advanced disease.

 [1]: pending:yes
Response to ß2-mimetics in asthmatic children: Which lung function parameters present reliable response?
Authors: Richard Kraemer, Gisela Wirz, Philipp Latzin, Oliver Fuchs
Journal: European Respiratory Journal (2012)

Rationale. Reversible airflow limitation after short-acting s2-agonist (SABA) is considered as a hallmark of asthma. However, in asthmatic children pulmonary hyperinflation significantly influences airway patency [1]. 'Effective' specific resistance (sReff) measures resistive changes throughout the whole breath cycle concomitantly to changes of resting end-expiratory level [2].

Objectives. Response to SABA assessed by various lung function parameters in asthmatic children.

Methods. Lung function measurements performed in 194 asthmatic children provided base-line (BL) data of functional residual capacity (FRCpleth), sReff, sRtot, volume-time and flow-volume indices such as FEV1, MEF50, and MMEF75-25, analysed as SDS by z-transformation using reference equations. Reversibility was considered, if after inhalation of 1.25 mg albuterol lung function improved > 2 SD from BL.

Results. Significant response to SABA was found for sRtot in 99.3%, sReff in 69.6%, MEF50in 46.8 %, MMEF75-25 in 23.2% FRCpleth in 15.5% and FEV1 in 3.6% of all 754 tests. In 12.5 % of tests, however, spirometry failed to indicate airway limitation at BL. Significant mean differences of improvement in SD were found for sReff 3.6±3.0, sRtot: 3.4±3.0, and MEF50: -2.0±2.52. Response to SABA was significantly higher in tests demonstrating airway obstruction only than in those with concomitant pulmonary hyperinflation (p< 0.001).

Conclusions. Compared to plethysmography, spirometry may fail detection of abnormal airway dynamics at BL, and otherwise only MEF50 reached significant response to SABA.

[1]. Kraemer R, et al.: J Pediatr 1983;102(3):347-350. [2]. Matthys H, et al.: Respiration 1975;32(2):121-134.
Brief Report: A Polymorphism in <i>TLR2</i> Is Associated With Arterial Thrombosis in a Multiethnic Population of Patients With Systemic Lupus Erythematosus
Authors: Rachel Kaiser, Ling Fung Tang, Kimberly E. Taylor, Kirsten Sterba, Joanne Nititham, Elizabeth E. Brown, Jeffrey C. Edberg, Gerald McGwin, Graciela S. Alarcón, Rosalind Ramsey‐Goldman, John D. Reveille, Luis M. Vilá, Michelle Petri, Joyce Rauch, Emily Miller, Kara Mesznik, Pui‐Yan Kwok, Robert P. Kimberly, Jane E. Salmon, Lindsey A. Criswell
Journal: Arthritis & Rheumatology (2014)

Thrombosis is a serious complication of systemic lupus erythematosus (SLE). Studies that have investigated the genetics of thrombosis in SLE are limited. We undertook this study to assess the association of previously implicated candidate genes, particularly Toll-like receptor (TLR) genes, with pathogenesis of thrombosis. We genotyped 3,587 SLE patients from 3 multiethnic populations for 77 single-nucleotide polymorphisms (SNPs) in 10 genes, primarily in TLRs 2, 4, 7, and 9, and we also genotyped 64 ancestry-informative markers (AIMs). We first analyzed association with arterial and venous thrombosis in the combined population via logistic regression, adjusting for top principal components of the AIMs and other covariates. We also subjected an associated SNP, rs893629, to meta-analysis (after stratification by ethnicity and study population) to confirm the association and to test for study population or ethnicity effects. In the combined analysis, the SNP rs893629 in the KIAA0922/TLR2 region was significantly associated with arterial thrombosis (logistic P = 6.4 × 10(-5) , false discovery rate P = 0.0044). Two additional SNPs in TLR2 were also suggestive: rs1816702 (logistic P = 0.002) and rs4235232 (logistic P = 0.009). In the meta-analysis by study population, the odds ratio (OR) for arterial thrombosis with rs893629 was 2.44 (95% confidence interval 1.58-3.76), without evidence for heterogeneity (P = 0.78). By ethnicity, the effect was most significant among African Americans (OR 2.42, P = 3.5 × 10(-4) ) and European Americans (OR 3.47, P = 0.024). TLR2 gene variation is associated with thrombosis in SLE, particularly among African Americans and European Americans. There was no evidence of association among Hispanics, and results in Asian Americans were limited due to insufficient sample size. These results may help elucidate the pathogenesis of this important clinical manifestation.
Randomized phase II study of decitabine in combination with carboplatin compared with carboplatin alone in patients with recurrent advanced ovarian cancer
Authors: R. M. Glasspool, M. Gore, G. Rustin, I. McNeish, R. Wilson, S. Pledge, J. Paul, M. Mackean, S. Halford, S. Kaye
Journal: Journal of Clinical Oncology (2009)

5562 Background: Experimental and clinical data (Gifford et al, Clin Cancer Res. 2004) indicate the potential importance of methylation in mediating resistance to carboplatin in ovarian cancer. A previous phase I trial (Appleton et al, J Clin Oncol. 2007) established the feasibility of combining carboplatin with the demethylating agent decitabine on a day 1 + 8 q4 weekly (w) schedule and PD data provided evidence of target cell demethylation. Methods: Patients (pt) with ovarian cancer relapsing 6–12 months following first line treatment were randomised to receive either 6 cycles of carboplatin AUC 6 q4 w (Arm A), or 90 mg/m 2 decitabine as a 6 hour infusion on day 1 and carboplatin AUC 6 on day 8 q4 w (Arm B). The primary endpoint was response rate. An interim analysis was planned after 11 patients were enrolled into Arm B. Results: 29 pt were enrolled. After the first 4 pt had been treated (at 90 mg/m 2 decitabine) the frequency of dose delays due to neutropenia was considered unacceptable, and therefore the starting dose of decitabine was reduced to 45 mg/m 2 for the subsequent 11 pt. 7 out of 14 pt in Arm A completed 6 cycles compared with 0 of 11 in Arm B (at 45 mg/m 2 decitabine). Grade 2/3 hypersensitivity reactions were more common in Arm B than Arm A (64% vs. 21%), as were prolonged treatment delays due to neutropenia (36% vs. 10%). At the interim analysis, in the 11 pt treated with 45mg/m 2 (Arm B), there were no RECIST responses, while 2 pt had short-lived CA125 responses (59 and 63 days). In contrast 6 of 14 patients in Arm A had RECIST responses consistent with the expected efficacy of carboplatin in this population. Conclusions: The lack of efficacy, as well as the difficulties in treatment delivery in Arm B, led the project team to conclude that the study should be closed. With this dose and schedule, decitabine is ineffective in reversing carboplatin resistance. Further investigations are ongoing to understand (a) the apparent increased incidence of hypersensitivity and (b) the trend towards reduced efficacy in Arm B. [Table: see text]
Loss of Myoepithelial Cell Characteristics in Metastasizing Rat Mammary Tumors Relative to Their Nonmetastasizing Counterparts&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: D J Dunnington, U Kim, C M Hughes, P Monaghan, E J Ormerod, P S Rudland
Journal: JNCI Journal of the National Cancer Institute (1984)

A series of WF rat mammary tumors comprising one transplantable nonmetastasizing line (MT-W9), two predominantly lymphatic (SMT-2A and SMT-077) and one lymphatic and hematogenous (MT-450) metastasizing transplantable lines, and 7,12-dimethylbenz[a]anthracene (DMBA)-induced nonmetastasizing primary tumors was examined for the presence of epithelial and myoepithelial cell characteristics with the use of immunocytochemical techniques. Tumor cells staining for myosin were only occasionally observed in a basal orientation in glandular structures in sections of DMBA-induced and MT-W9 tumors; anti-laminin serum stained the peripheries of the glandular structures in the DMBA-induced and MT-W9 tumors but failed to stain the SMT-2A and SMT-077 tumor cells. In the nonmetastasizing tumors immunologically detectable keratin occurred mainly in the outer cellular layer of glandlike structures, whereas milk fat globule membrane immunoreactivity occurred primarily in the luminal cells. Both these types of immunoreactivity were observed in MT-450 tumor cells, but the pattern of keratin staining was random. No such immunoreactivity occurred in SMT-2A or SMT-077 tumors. No tumor cell-associated staining for fibronectin was seen in any of the tumors examined, although host stromal components stained intensely. The nonmetastasizing tumors contained cuboidal epithelial cells with lumen formation, surface microvilli, and intercellular junctional complexes, together with a relatively undifferentiated elongated cell component. Other elongated cells showed hemidesmosomes, pinocytotic vesicles, tonofilaments, and small bundles of cytoplasmic filaments, suggesting gradations toward a myoepithelial phenotype. The MT-450 tumors were ultrastructurally similar to the nonmetastasizing tumors, but no features of myoepithelial cells were seen, although some cuboidal epithelial cells exhibited prominent tonofilaments. The SMT-2A and SMT-077 tumors consisted of nests of cuboidal-like cells with highly pleomorphic nuclei and much intercellular collagen. The results indicate a progressive loss of cellular differentiation characteristics, particularly those of the myoepithelial cell with increasing malignancy in this system.