tbuckley/cabot-search huggingface dataset:
Histological correlates of vascular density analysis by computer tomography in chronic obstructive pulmonary disease (COPD)
Authors: Gemma Argemí, David Domínguez-Fandos, Farbod Rahaghi, Raúl San José-Estepar, Pedro Arguis, Victor Peinado, George Washko, Joan Albert Barberà
Journal: European Respiratory Journal (2014)

INTRODUCTION: Changes in pulmonary vessels in COPD are complex due to vascular remodeling and emphysema. Quantitative assessment of pulmonary vascular morphology on CT scan provides a unique measure of disease severity. We aimed to evaluate the relationships between CT density of pulmonary vessels and morphological assessments in COPD.  METHODS:39 patients undergoing lung resection for localized neoplasm were studied (7 nonsmokers, 8 smokers with normal lung function and 24 COPD patients). Density of vessels   RESULTS: There was a trend in COPD to lower CSA-CT, compared with nonsmokers (p=0.07). The PA/A ratio did not differ between groups. At the histological analysis, COPD patients had similar vessel density (CSA-Hist), less bronchioles (p=0,02) and less alveolar septa (p=0.001). In the whole population, CT assessed vessel density (CSA-CT) correlated with septal density (r=0.37,p  CONCLUSION: In COPD, assessment of pulmonary vascular density by CT correlates with the microscopic integrity of lung parenchyma and small arteries.
Fortnightly Review: Management of hip osteoarthritis
Authors: P. Dieppe
Journal: BMJ (1995)

Osteoarthritis of the hip is a common disorder of white (but not black) people with a roughly equal incidence in both sexes.Although more common in elderly people, it may start at any age from the second or third decade.Most cases are idiopathic, even among younger people, though a minority are secondary to a congenital or childhood hip disorder (acetabular dysplasia, congenital dislocation, slipped epiphysis, or Perthe's disease) or to an inflammatory arthropathy.'Other risk factors for osteoarthritis may include inequalities in leg length and certain occupations or patterns of use of the hip: for example, there is a strong association between farming and hip osteoarthritis in European men.2The condition has a chronic, variable course and often causes considerable pain and dis- ability.Good management depends on the doctor's ability to diagnose the condition early, appreciate factors that may affect the prognosis or complicate the disease, and make effective use of the many treatment methods available. Presentation, diagnosis, and prognosisThe start of symptomatic hip osteoarthritis is usually insidious, although in a few cases pain starts abruptly.
The N-Hydroxylation of 4-Acetylaminobiphenyl by the Rat and Dog and the Strong Carcinogenicity of N-Hydroxy-4-acetylaminobiphenyl in the Rat
Authors: James A. Miller, Carole S. Wyatt, Elizabeth C. Miller, Henrik A. Hartmann
Journal: Cancer Research (1961)

Summary   N -Hydroxy-4-acetylaminobiphenyl has been identified as a urinary metabolite of the carcinogens 4-acetylaminobiphenyl and 4-aminobiphenyl in the rat. 4-Acetylaminobiphenyl, but not 4-aminobiphenyl, yielded the same metabolite in the dog. The  N -hydroxy metabolite was excreted as a conjugate which was easily cleaved by a bacterial β-glucuronidase preparation but not by Takadiastase. The identity of the metabolic  N -hydroxy-4-acetylaminobiphenyl was established by its isolation in crystalline form and comparison with the synthetic compound. In opposition to the situation previously observed with 2-acetylaminofluorene in the rat,  N -hydroxy-4-acetylaminobiphenyl was found in gradually decreasing amounts in the urine as the feeding of 4-acetylaminobiphenyl to rats progressed over several months. Upon oral administration to adult female rats  N -hydroxy-4-acetylaminobiphenyl was as active a mammary carcinogen as 4-acetylaminobiphenyl and also induced more ear-duct carcinomas and forestomach papillomas than the parent amide. Upon repeated intraperitoneal injection into young female rats  N -hydroxy-4-acetylaminobiphenyl was more active than 4-acetylaminobiphenyl as a mammary carcinogen. Dietary 3-methylcholanthrene had no marked effect on the  N -hydroxylation of 4-acetylaminobiphenyl or on the carcinogenicity of this amide and its  N -hydroxy metabolite toward the mammary gland.  N -Hydroxy-4-acetylaminobiphenyl appears to be one of the proximate agents in carcinogenesis by 4-acetylaminobiphenyl in the rat.
Shaken Baby Syndrome
Authors: John B P Stephenson
Journal: Journal of the Royal Society of Medicine (2003)

With the December 2002 issue of the JRSM I received a colour brochure advertising the European Conference on Shaken Baby Syndrome, to be held in Edinburgh in May 2003. The chief sponsor is the National Center on Shaken Baby Syndrome, USA, but supporters include the RSM. Shaken baby syndrome (or shaken impact syndrome) is a hypothetical condition, albeit believed in by some with a religious passion. In the hurly-burly of full-time paediatric neurological practice I used to believe in it myself; however, within the past two years publications from several centres have critically questioned the assumptions underlying the concept and the diagnosis1,2,3,4,5,6,7. If the purpose of the conference is scientific enquiry and rational discourse, it is surprising that the authors of these publications are entirely absent from the list of invited speakers.
First and final report of a phase II study of the poly(ADP-ribose) polymerase (PARP) inhibitor, AG014699, in combination with temozolomide (TMZ) in patients with metastatic malignant melanoma (MM)
Authors: R. Plummer, P. Lorigan, J. Evans, N. Steven, M. Middleton, R. Wilson, K. Snow, R. Dewji, H. Calvert
Journal: Journal of Clinical Oncology (2006)

8013 Background: Inhibition of PARP and thus Base Excision Repair has been shown to potentiate the cytotoxicity of DNA damaging agents preclinically. A Phase I study of AG014699 + TMZ reported at ASCO 2005 showed that a full dose of TMZ could be given in the presence of profound PARP inhibition. We report the results of a Phase II study of AG014699 12 mg/m 2 and TMZ 200 mg/m 2 5x daily q 4 weekly in patients with advanced MM. This Phase II study commenced in March 2005 and completed recruitment in December 2005. Methods: Patients with measurable MM who were chemotherapy naïve, performance status ≤ 2, and had standard blood indices for early trials were recruited. Patients with ocular melanoma or brain metastases were excluded. Treatment was given until progression, with repeat imaging every 2 cycles. A two stage phase II design was used, with the hypothesis to be tested that the response rate to TMZ would be increased to 25%. α and β error rates were set at 0.10. 27 patients were recruited into the first stage with continuation to 40 patients if ≥3 partial responses were observed. Results 40 patients who fulfilled the eligibility criteria were recruited and treated. The required 3 responses were seen at an early stage. More enhancement of TMZ associated myelosuppression by the addition of AG014699 has been observed compared to the phase I study (Grade 4 thrombocytopenia 12% cycles, grade 4 neutropenia 15% to date). There has been one toxic death in cycle 1 (febrile neutropenia), 3 further patients hospitalised with myelosuppression and 12 patients in total requiring dose reduction of TMZ to 150 mg/m 2 (1 to 100 mg/m 2 ). All of these patients continued treatment at the reduced dose. Other toxicities have been fatigue and mild nausea. Currently there are 4 confirmed partial responses, 4 prolonged disease stabilisations and 20 patients are too early to evaluate. Conclusions The combination of TMZ and AG014666 shows encouraging activity in MM. Myelosuppression is greater than would be expected with single agent TMZ. PARP expression and activity in blood cells and tumour will be correlated with the mature outcome data from the trial. [Table: see text]
Low-dose filgrastim significantly enhances neutrophil recovery following autologous peripheral-blood stem-cell transplantation in patients with lymphoproliferative disorders: evidence for clinical and economic benefit.
Authors: I G McQuaker, A E Hunter, S Pacey, A P Haynes, A Iqbal, N H Russell
Journal: Journal of Clinical Oncology (1997)

PURPOSE To assess the clinical and economic benefit of low-dose (50 microg/m2) filgrastim after peripheral blood stem-cell transplantation (PBSCT) in a randomized, placebo-controlled double-blinded study. PATIENTS AND METHODS Thirty-eight patients with lymphoproliferative disorders were randomized to receive low-dose filgrastim (19 patients) or placebo (19 patients) beginning on the first day after stem-cell reinfusion and continuing until absolute neutrophil count (ANC) was greater than 0.5 x 10(9)/L. All patients received greater than 2.5 x 10(6) CD34+ cells/kg, which was mobilized with chemotherapy and filgrastim 300 microg from the fifth day. An economic analysis was performed based on the outcome in the two groups. RESULTS Neutrophil engraftment was significantly more rapid in patients who received filgrastim with a median number of days until ANC was greater that 0.5 x 10(9)/L of 10 (9 to 13) versus 14 (9 to 19; P &lt; .0001). The time to reach an ANC greater than 1 x 109/L was 12 (9 to 14) versus 16 days (10 to 25; P &lt; .0001). The total number of patients who required intravenous antibiotic therapy was lower in the filgrastim-treated group (68%) compared with the placebo group (89%); also, the median number of days with fever and the duration of antibiotic therapy were shorter, although these differences did not reach statistical significance. However, although only three of 19 (16%) patients who received filgrastim required amphotericin, 11 of 19 (58%) who received placebo did require it, and amphotericin usage was significantly less in the filgrastim group (P = .029). Finally, in-patient stay was significantly shortened in those who received filgrastim from 16 (13 to 23) to 13 days (11 to 18; P = .0003). CONCLUSION Low-dose filgrastim significantly reduces neutrophil engraftment time post-PBSCT and also reduces in-patient stay and costs, which makes it economically viable for patients who are undergoing high-dose chemotherapy.
Thromboembolic complications after perioperative chemotherapy in women with early breast cancer: a European Organization for Research and Treatment of Cancer Breast Cancer Cooperative Group study.
Authors: P C Clahsen, C J van de Velde, J P Julien, J L Floiras, F Y Mignolet
Journal: Journal of Clinical Oncology (1994)

PURPOSE AND METHODS Data from a randomized phase III trial in early breast cancer, comparing surgery followed by one short intensive course of perioperative fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus surgery alone, were analyzed for the occurrence of thromboembolic complications within 6 weeks after surgery. RESULTS Twenty-seven of 1,292 patients assigned to the perioperative chemotherapy treatment arm (2.1%) and 10 of 1,332 patients on observation (0.8%) developed thromboembolic events (P = .004). The frequency of thromboembolic complications was higher among postmenopausal women compared with premenopausal women (2.0% v 0.6%, P = .003). Patients who had mastectomy had a higher frequency of thromboembolic disease than those who had tumorectomy (2.3% v 0.7%, P &lt; .001). Three deaths occurred after pulmonary embolism, all of them in the perioperative chemotherapy treatment arm. CONCLUSION These results suggest a contributing role of perioperative chemotherapy to thromboembolic disease, especially in postmenopausal women and women undergoing mastectomy. Antithrombosis prophylaxis should be considered in the case of adjuvant perioperative chemotherapy.
Comparison of different measurement methods of gas diffusion in the lung
Authors: Alexandra M. Preisser, Maxi Seeber, Xaver Baur
Journal: European Respiratory Journal (2012)

Background:

Lung fibrosis results in decreases of oxygen diffusion and oxygen arterial partial pressure (Pa,O2) especially during exercise. Obstructive airway diseases are often associated with a mismatch of ventilation and perfusion. We investigated the validity of the CO diffusion capacity (DL,CO) in comparison with Pa,O2 and alveolo-arterial oxygen gradient (AaDO2) in different lung diseases.

Methods:

250 subjects (52.3±12.5 yrs) were examined, out of 206 there were: 13 with VC LLN), and 88 healthy controls. Pearson correlation coefficient of DL,CO with Pa,O2 and AaDO2 were analyzed in each group.

Results:

DL,CO (%pred.), Pa,O2 at rest, and AaDO2, respectively, showed low correlation in all groups (0.25**; -0.19\*)(\**=p<0.001, *=p<0.01). DL,CO and Pa,O2 during exercise revealed moderate correlation in the group with bronchial obstruction (0.55**), but there were strong correlations in the groups with reduced VC and/or DL,CO (0.82**; 0.68*). Correlations between DL,CO and AaDO2 during exercise were the best in the latter two groups (-0.84**; -0.64*), medium in the group with bronchial obstruction (-0.47**), but not significant in healthy controls (0.19).

Conclusions: Only in patients with reduced VC and/or impaired DL,CO all three parameters are likely to objectify impaired gas exchange in the lungs. AaDO2 relates to the ventilation, this may be the cause of the good correlation with DL,CO. In the group with bronchial obstruction DL,CO seems to be influenced by other pathophysiological aspects, resulting in only moderate correlation between the different parameters.
Abstract 4238: Speckle Tracking Echocardiography can Identify the Location of Myocardial Injury in Acute Myocarditis
Authors: Fabien Hyafil, Jean-Michel Serfaty, Gregory Ducrocq, David Messika-Zeitoun, Philippe G Steg, Jean-Pierre Laissy, Eric Brochet, Alec Vahanian
Journal: Circulation (2008)
Male Subfertility
Authors: H. A. Davidson
Journal: BMJ (1949)

HERPES ZOSTER AFTER IRRADIATION BEDICJOHL necessary details for such correlation were not available in our cases, the provision of the necessary minutiae in the usual treatment notes being impracticable as a routine.)The relative rarity of zoster in patients treated with x rays, even when the region of the spine is directly treated, suggests that patients vary in their sensitivity either accord- ing to the degree of fibrous reaction or according to the presence of the dormant virus.Even in a large group of cases of carcinoma of the breast treated by a similar post-operative technique the percentage developing zoster is small.A factor that may be important is that of immunity conferred by a previous attack of zoster or varicella.On the other hand, zoster developing after a prolonged period after irradiation-e.g., more than 24 months later-is likely to be purely coincidental.Previous attempts to correlate zoster with cancer or reti- culosis have been based on the hypothesis that the zoster was due to infiltration by the underlying disease of the spinal ganglia or other parts of the afferent nervous reflex arc.No other authors seem to have correlated the inci- dence of zoster with the administration of x-ray treatment in a large series where such infiltration was absent.Summary A series of 45 cases of zoster developing after irradiation is described.The literature concerning the connexion between zoster on the one hand and malignant disease and reticulosis on the other is reviewed.Evidence is adduced to suggest that irradiation is implicated in the development of zoster in the majority of the cases described.
Th1/Th2 cytokine response in infants with lower respiratory tract infection: Can we predict wheezing?
Authors: Ivane Chkhaidze, Dali Zirakishvili, Neli Barnabishvili, Ketevan Gogvadze
Journal: European Respiratory Journal (2013)

Aim  The aim of the study was to assess the relationship among cytokine response in lower respiratory tract illness (LRTI) with wheezing in infancy and frequency of wheezing episodes later, in preschool age.  Methods  45 Infants younger than 3 years of age admitted to Iashvili central children hospital of Tbilisi, between January 2010 and December 2011, with an acute episode of wheezing associated with LRTI were selected.  Levels of tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-6 (IL-6) in blood were evaluated by ELISA at admission to the clinic. IgE concentration also was assessed. The association between wheezing and familial, pre- and postnatal risk factors also was investigated. The follow-up study consisted of physical examination and/or written questionnaire.  Results  At follow-up, 12 children (27%) had recurrent wheezing. Cytokine responses were analyzed in relation to the development of recurrent episodes of wheezing during a 2-year follow-up period. IL-6 and TNF-alpha levels during LRTI turned out to be higher in infants that later developed wheezing. No association was found between IFN-gamma responses and recurrent wheezing.  Atopy in infancy was associated with the increased risk for wheezing (OR:7.4; 95% confidence interval [CI]: 1.799 to 30.994).  Conclusions  Our results suggest that characteristics of the immune system present during the infancy might anticipate the likelihood of development of episodes of airway obstruction in preschool age. Longer follow-up is required to better understand the role of these cytokines, as well as risk factors, in the development of bronchial obstruction.
Phase 1 study with BIBW 2992, an irreversible dual tyrosine kinase inhibitor of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) in a 2 week on 2 week off schedule
Authors: C. H. Mom, F. A. Eskens, J. A. Gietema, K. Nooter, M. J. De Jonge, A. Amelsberg, H. Huisman, P. Stopfer, E. G. De Vries, J. Verweij
Journal: Journal of Clinical Oncology (2006)

3025 Background: BIBW 2992 is a highly selective, potent, irreversible tyrosine inhibitor of EGFR and HER2. A phase 1 study of orally administered BIBW 2992 was performed to determine its safety, PK and PD. Methods: Patients (pts) with advanced solid malignancies received BIBW 2992 once daily (OD) for 2 weeks, in 4 week cycles. Adverse events were evaluated according to CTCv3.0 and tumor response according to RECIST. In cycle 1 and 2, BIBW 2992 plasma PK analysis was performed. Before and after cycle 1, biomarkers involved in EGFR activation were assessed in skin biopsies. Results: 38 pts received 10 mg (n=3), 20 mg (n=3), 30 mg (n=3), 45 mg (n=3), 70 mg (n=18), 100 mg (n=2) and 85 mg (n=6) OD. At 100 mg dose-limiting toxicities (DLTs) consisted of grade 3 skin rash (n=1) and grade 3 diarrhea despite loperamide (n=1). At the dose level of 85 mg, DLTs were seen in 2 pts (diarrhea in both). An additional 12 pts were subsequently enrolled at 70 mg. A total of 3 DLTs was seen in the 18 pts treated at 70 mg (all 3 diarrhea, in one case with additional grade 3 nausea and ALT increase). In other pts, diarrhea was controllable with loperamide, whereas skin events could be ameliorated with minocycline. The dose of 70 mg BIBW 2992 OD was therefore set as the recommended phase 2 dose. Exposure (AUC 0-∞ and AUC τ,ss range 82–2080 ng·h/mL) and peak plasma concentrations (C max and C max,ss range 7–150 ng/mL) increased with increasing doses. High interpatient variability in all PK parameters was found, but was within the range expected for an orally administered drug. The volume of distribution (V z /F) ranged from 800–2900 L, indicating high tissue distribution. Median t max values ranged between 1–4 h. The gMean terminal t 1/2 ranged between 13–32 h. Accumulation ratio based on AUC was between 2–2.9. Steady state was reached around day 8. After cycle 1, a &gt;20% reduction in Ki-67 (range 20–83%), reflecting inhibition of keratinocyte proliferation, was seen in paired skin biopsies of 31 pts. Ki-67 positive cells (mean ± SD) decreased from 14 ± 4.5% pre-treatment to 7.9 ± 4.5% on day 13 (p&lt;0.0001). SD lasting ≥4 cycles occurred in 8 pts. Conclusions: 70 mg BIBW 2992 OD can be safely administered in a 2 week on, 2 week off schedule. Further evaluation in phase 2 trials in warranted. [Table: see text]
Ibrutinib Treatment of Relapsed CLL Following Allogeneic Transplantation: Sustained Disease Response and Promising Donor Immune Modulation
Authors: Christine E. Ryan, Aaron C. Logan, Andrew Rezvani, Manali Kamdar, Hideki Nakasone, Bita Sahaf, Joanne Otani, Katherine A Kong, Mark Klinger, Malek Faham, Steven Coutre, David B. Miklos
Journal: Blood (2014)
The potential role of the pequi fruit (caryocar braziliense camb) in the prevention of lung cancer in an experimental model
Authors: Natália B.R. Colombo, Edwin Roger Parra, César Koppe Grisolia, Márcia Hage, Denise Barbeiro, Vera Luíza Capelozzi
Journal: European Respiratory Journal (2013)

The aim of this study was to evaluate the expression of the isoforms of the oxid nitric synthase (Nos1, Nos 2, Nos 3)and the antioxidant activity of the pequi pulp ethanolic extract and oil, measuring lipid peroxidations and DNA damage in an experimental modelo f lung cancer induced by urethane. Methods: 25 male BALB/c mice that received two intraperitoneal doses of urethane (Ugroup = 5).10 mices received by gavage 3μg/kg of the extract (UEgroup = 10). 10 animals received by gavage 15μL of the oil (UOgroup=10). After 75 days, the tree groups were sacrificed. The expression of the NOSs isoforms were estimated by imunohistochemestry and the antioxidant activity of pequi oil and extract was evaluated by TBARS test and by the comet test method. Results:The lung parenchyma from the Urethane groups showed neoplastic formations induced by the chemical carcinogenesis. The imunohistochemestry for analysis of the NOSs isoforms didn’t show a significant difference. The image analysis of the comet assay showed a statistical significant decreased of the DNA damage cells in the Urethane + Extract group (p=0.02) and the UOgroup (p=0.001) when compared with U. Group. The results of TBARS also showed a significant decreased of lipid peroxidation in the UE group (p=0.02) and a marginal decreased of the UOgroup (p=0.08) when compared with the U. Group. Conclusion: We conclude that the pequi oil and extract are efficient to diminish the oxidative stress and lipid peroxidation in chemical carcinogenesis induced by urethane. These results suggest that the different natural antioxidant components found in the pequi fruit might be an strategy in the prevention of the lung cancer.