tbuckley/cabot-search huggingface dataset:
Early [18F]Fluorodeoxyglucose Positron Emission Tomography at Two Days of Gefitinib Treatment Predicts Clinical Outcome in Patients with Adenocarcinoma of the Lung
Authors: Ryo Takahashi, Haruhiko Hirata, Isao Tachibana, Eku Shimosegawa, Atsuo Inoue, Izumi Nagatomo, Yoshito Takeda, Hiroshi Kida, Sho Goya, Takashi Kijima, Mitsuhiro Yoshida, Toru Kumagai, Atsushi Kumanogoh, Meinoshin Okumura, Jun Hatazawa, Ichiro Kawase
Journal: Clinical Cancer Research (2011)

Positron emission tomography (PET) with [(18)F]fluorodeoxyglucose (FDG) is increasingly used in early assessment of tumor response after chemotherapy. We investigated whether a change in [(18)F]FDG uptake at 2 days of gefitinib treatment predicts outcome in patients with lung adenocarcinoma.Twenty patients were enrolled. [(18)F]FDG-PET/computed tomographic (CT) scan was carried out before and 2 days after gefitinib treatment. Maximum standardized uptake values (SUV) were measured, and post-gefitinib percentage changes in SUV were calculated. Early metabolic response (SUV decline < -25%) was compared with morphologic response evaluated by CT scan and with progression-free survival (PFS).At 2 days of gefitinib treatment, 10 patients (50%) showed metabolic response, 8 had metabolic stable disease, and 2 had progressive metabolic disease. Percentage changes of SUV at 2 days were correlated with those of tumor size in CT at 1 month (R(2) = 0.496; P = 0.0008). EGFR gene was assessable in 15 patients, and of 12 patients with EGFR mutations, 8 showed metabolic response at 2 days and 6 showed morphologic response at 1 month. None of 3 patients with wild-type EGFR showed metabolic or morphologic response. Metabolic response at 2 days was not statistically associated with PFS (P = 0.095), but when a cutoff value of -20% in SUV decline was used, metabolic responders had longer PFS (P < 0.0001).Early assessment of [(18)F]FDG tumor uptake with PET at 2 days of gefitinib treatment could be useful to predict clinical outcome earlier than conventional CT evaluation in patients with lung adenocarcinoma.
Split-night versus full-night studies for sleep apnoea/hypopnoea syndrome
Authors: N. McArdle, A. Grove, G. Devereux, L. Mackay-Brown, T. Mackay, N.J. Douglas
Journal: European Respiratory Journal (2000)

Investigation and treatment of sleep apnoea/hypopnoea syndrome (SAHS) is placing increasing demands on healthcare resources. This workload may be reduced by using split-night studies instead of the standard full-nights of diagnostic polysomnography and continuous positive airway pressure (CPAP) titration. Split-night studies involve polysomnography in the first half of the night followed, if there is an abnormal frequency of apnoeas and hypopneas, by CPAP titration for the remainder of the night. The authors9 database of all patients prescribed a CPAP trial 1991-1997 was used to compare long-term outcomes in all 49 (46 accepting CPAP) patients prescribed split-night studies with those in full-night patients, matched 1:2 using an apnoea/ hypopnoea index (AHI) of +/-15% and Epworth score of +/-3 units. Classical symptoms of SAHS were the main reason for the split-night studies (n=27). There were no differences between the groups in long-term CPAP use, median nightly CPAP use (split-night 6.0 h x night-1, interquartile range (IQR) 3.8-7.4, full-night; 6.2 h x night-1, IQR 3.7-7.0, p=0.9), post-treatment Epworth scores and frequency of nursing interventions/clinic visits required. The median time from referral to treatment was less for the split-night patients (13 months, IQR 11-20 months) than for full-night patients (22 months, IQR 12-34 months; p=0.003). Split-night studies, in selected patients, result in equivalent long-term continuous positive airway pressure use to full-night studies with shorter treatment times and less healthcare utilization.
Unresolved Grief in a National Sample of Bereaved Parents: Impaired Mental and Physical Health 4 to 9 Years Later
Authors: Patrizia K. Lannen, Joanne Wolfe, Holly G. Prigerson, Erik Onelov, Ulrika C. Kreicbergs
Journal: Journal of Clinical Oncology (2008)

To assess unresolved parental grief, the associated long-term impact on mental and physical health, and health service use.This anonymous, mail-in questionnaire study was performed as a population-based investigation in Sweden between August 2001 and October 2001. Four hundred forty-nine parents who lost a child as a result of cancer 4 to 9 years earlier completed the survey (response rate, 80%). One hundred ninety-one (43%) of the bereaved parents were fathers, and 251 (56%) were mothers. Bereaved parents were asked whether or not, and to what extent, they had worked through their grief. They were also asked about their physical and psychological well-being. For outcomes of interest, we report relative risk (RR) with 95% CIs as well as unadjusted odds ratios and adjusted odds ratios.Parents with unresolved grief reported significantly worsening psychological health (fathers: RR, 3.6; 95% CI, 2.0 to 6.4; mothers: RR, 2.9; 95% CI, 1.9 to 4.4) and physical health (fathers: RR, 2.8; 95% CI, 1.8 to 4.4; mothers: RR, 2.3; 95% CI, 1.6 to 3.3) compared with those who had worked through their grief. Fathers with unresolved grief also displayed a significantly higher risk of sleep difficulties (RR, 6.7; 95% CI, 2.5 to 17.8). Mothers, however, reported increased visits with physicians during the previous 5 years (RR, 1.7; 95% CI, 1.1 to 2.6) as well as a greater likelihood of taking sick leave when they had not worked through their grief (RR, 2.1; 95% CI, 1.2 to 3.5).Parents who have not worked through their grief are at increased risk of long-term mental and physical morbidity, increased health service use, and increased sick leave.
Risk factors for Mycobacterium tuberculosis infection among contacts of pulmonary tuberculosis patients
Authors: Jae Seuk Park, Do Hyung Kim, Jee Young Kang
Journal: European Respiratory Journal (2012)

Background:  Detection and treatment of tuberculosis(TB) infection with contact investigation is a key component of TB control program. We evaluated the risk factors for TB infection among contacts of recently diagnosed pulmonary TB patients in a tertiary hospital in Korea, an intermediate incidence country.  Methods:  206 contacts of 90 adult pulmonary TB patients underwent tuberculin skin test(TST) and chest radiography. The TST results were considered positive with induration of 10 mm or more, suggesting TB infection. A standardized questionnaire was used to assess risk factors associated with TB infection.  Results:  TST was positive in 97 of 206 contacts of TB patients(47.1%) and TST positive rate increased with age. The risk of TB infection was significantly associated with close contact with TB patients(sleeping in the same room)(OR=4.94, 95% CI = 1.43-17.00).   Conclusion : TB infection rate was higher in elderly, and risk of TB infection was significantly increased with close contact of TB patients.
Efficacy and safety of novel oral anticoagulants for treatment of acute venous thromboembolism: direct and adjusted indirect meta-analysis of randomised controlled trials
Authors: B. D. Fox, S. R. Kahn, D. Langleben, M. J. Eisenberg, A. Shimony
Journal: BMJ (2012)

<b>Objective</b> To critically review the effectiveness of the novel oral anticoagulants (rivaroxaban, dabigatran, ximelagatran, and apixaban) in the treatment of acute venous thromboembolism. <b>Design</b> Systematic review and random effects meta-analysis. Data were extracted independently by two investigators. An adjusted indirect comparison was performed to compare between novel oral anticoagulants. <b>Data sources</b> Medline, Embase, and Cochrane Library (from inception to April 2012). Hand searching of relevant scientific works and contact with experts. <b>Study selection</b> Randomised controlled trials of novel oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism. Selected outcomes were recurrent events, major bleeding, and all cause mortality. <b>Results</b> Nine studies met our inclusion criteria, involving 16 701 patients evaluated for efficacy and 16 611 for safety. Data were stratified according to different novel oral anticoagulants. For recurrent acute venous thromboembolism, there were no significant differences in events rates between any of the anticoagulants and conventional treatment (rivaroxaban (four studies): relative risk 0.85, 95% confidence interval 0.55 to 1.31; dabigatran (two studies): 1.09, 0.76 to 1.57; ximelagatran (two studies): 1.06, 0.62 to 1.80; and apixaban (one study): 0.98, 0.20 to 4.79). Rivaroxaban reduced the risk of major bleeding compared with conventional treatment (0.57, 0.39 to 0.84), whereas other novel oral anticoagulants did not (0.76 (0.49 to 1.18) for dabigatran; 0.54 (0.28 to 1.03) for ximelagatran; 2.95 (0.12 to 71.82) for apixaban). For all cause mortality there were no significant differences between the novel oral anticoagulants and conventional treatment (0.96 (0.72 to 1.27) for rivaroxaban; 1.00 (0.67 to 1.50) for dabigatran; 0.67 (0.42 to 1.08) for ximelagatran; 6.89 (0.36 to 132.06) for apixaban). The adjusted indirect comparison between rivaroxaban and dabigatran did not show superiority of either drug over the others for major bleeding (0.75, 0.41 to 1.34) or the other endpoints. <b>Conclusions</b> Compared with vitamin K antagonists, the novel oral anticoagulants had a similar risk of recurrence of acute venous thromboembolism and all cause mortality, though rivaroxaban was associated with a reduced risk of bleeding.
Repetitive monomorphic ventricular tachycardia originating from the aortic sinus cusp
Authors: Feifan Ouyang, Parwis Fotuhi, Siew Yen Ho, Joachim Hebe, Marius Volkmer, Masahiko Goya, Mark Burns, Matthias Antz, Sabine Ernst, Riccardo Cappato, Karl-Heinz Kuck
Journal: Journal of the American College of Cardiology (2002)
Pulmonary hypertension: diagnosis and management
Authors: D. G. Kiely, C. A. Elliot, I. Sabroe, R. Condliffe
Journal: BMJ (2013)

#### Summary points

Pulmonary hypertension was previously considered a rare untreatable condition. The past two decades have seen major changes in our understanding of the spectrum of disease affecting the pulmonary circulation. More than 30 randomised controlled trials (RCTs) of treatments have been performed, and surgery for patients with chronic thromboembolic pulmonary hypertension has been developed. Advances in imaging have enabled more detailed patient assessment, but pulmonary hypertension continues to be a life shortening condition, and there is often a delay of around two years from onset of symptoms to diagnosis.1 This article focuses on adult pulmonary hypertension in primary and secondary care, its diagnosis, and management.

#### Sources and selection criteria

This review is based on our personal experience, personal archives of references, and a PubMed search using terms including pulmonary hypertension, chronic thromboembolic disease, and prognosis. We consulted international guidelines from the European Society of Cardiology, European Respiratory Society, and American College of Chest Physicians.

Pulmonary hypertension is defined at cardiac catheterisation as a mean pulmonary artery pressure of 25 mm Hg or more. The initial clinical classification in 1973 arose from a World Health Organization sponsored international meeting after an epidemic related to use of …
Vitamin E Protects against Lipid Peroxidation and Rescues Tumorigenic Phenotypes in Cowden/Cowden-like Patient-Derived Lymphoblast Cells with Germline <i>SDHx</i> Variants
Authors: Ying Ni, Charis Eng
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Cowden syndrome (CS), a Mendelian autosomal-dominant disorder, predisposes to breast, thyroid, and other cancers. Germline variations in succinate dehydrogenase genes (SDHx) occur in approximately 10% PTEN mutation-negative CS and CS-like (CSL) individuals (SDHvar+). We previously showed that SDHx variants result in elevated reactive oxygen species (ROS), disruption of nicotinamide adenine dinucleotide (NAD) equilibrium, and destabilization of p53 hence apoptosis resistance in CS/CSL patient-derived lymphoblastoid cells. In the present study, we sought to address the tumorigenic impacts of increased ROS and the potential of protecting SDHvar+ cells with antioxidants. Experimental Design: We measured the lipid peroxidation levels in patient-derived SDHvar+ lymphoblastoid cells and sequenced 74 controls or SDHvar+ germline DNA samples for mitochondrial hypervariable region II (HVRII) polymorphisms. SDHvar+ lymphoblastoid cells were treated with various antioxidants to check p53 expression and sub-G1 cell population with cell-cycle analysis. Results: We showed that elevated ROS results in higher lipid peroxidation in SDHvar+ cells. Accumulation of polymorphisms in mitochondrial HVRII was observed in SDHvar+ samples. Interestingly, α-tocopherol (vitamin E) treatment, but not other antioxidants, rescued SDHvar+ cells from apoptosis resistance and protected SDHvar+ cells from oxidative damage such as decreased lipid peroxidation as well as partially recovered p53 expression and NAD/NADH levels. Conclusions: We conclude that disruption of complex II because of SDHx variants leads to increased ROS generation, specifically accompanied by lipid peroxidation. The lipid soluble antioxidant α-tocopherol can selectively protect SDHvar+ cells from oxidative damage, apoptosis resistance, and rebalance redox metabolites NAD/NADH. Clin Cancer Res; 18(18); 4954–61. ©2012 AACR.
Pattern of Emphysema Distribution in α1-Antitrypsin Deficiency Influences Lung Function Impairment
Authors: David G. Parr, Berend C. Stoel, Jan Stolk, Robert A. Stockley
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

FEV(1) is fundamental to the diagnosis and staging of chronic obstructive pulmonary disease. In emphysema, airflow obstruction usually coexists with impairment of gas exchange, but discordance is not infrequent. We hypothesized that variations in the distribution of emphysema would be associated with functional differences and therefore account for discordant physiology. We used quantitative computed tomography to assess emphysema severity and distribution in 119 subjects with alpha1-antitrypsin deficiency (PiZ phenotype) and grouped them according to distribution pattern. In the 102 subjects with emphysema, 65 had a predominantly basal pattern ("basal"), but 37 (36%) had greater involvement of the upper regions ("apical"). Subjects from each group were matched for total volume of emphysema and age, and matched pairs analysis was used to relate emphysema distribution to clinical phenotype. Basal distribution was associated with greater impairment of FEV(1) (mean difference, 9.9% predicted; 95% confidence interval, 3.8 to 16.0; p = 0.002) but less impairment of gas exchange (Pa(O(2)) mean difference, 0.5 kPa, 0.03 to 0.1; p = 0.016) and alveolar-arterial oxygen gradient (mean difference, 0.7 kPa; 0.2 to 1.2; p = 0.007) than the apical distribution. Emphysema distribution correlated with physiologic discordance (r = -0.409, p < 0.001). The use of single physiologic parameters as a surrogate measure of emphysema severity may introduce systematic bias in the staging of subjects with emphysema.
Phase II Trial of CHOP Plus Rituximab in Patients With HIV-Associated Non-Hodgkin's Lymphoma
Authors: François Boué, Jean Gabarre, Christian Gisselbrecht, Jacques Reynes, Antoine Cheret, Fabrice Bonnet, Eric Billaud, Martine Raphael, Remi Lancar, Dominique Costagliola
Journal: Journal of Clinical Oncology (2006)

To evaluate the safety and efficacy of rituximab adjunction to the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen in patients with newly diagnosed AIDS-related non-Hodgkin's lymphoma.HIV-seropositive patients with high-grade lymphoma of B-cell origin were eligible if they had no more than one of the following characteristics: CD4 cell count less than 100/microL, prior AIDS, or performance status less than 2. This multicenter phase II trial evaluated the response rate and disease-free survival after six courses of rituximab plus CHOP. Results Sixty-one patients were enrolled. All the patients were assessable for safety and 52 were assessable for the tumor response after treatment completion. Characteristics of patients were median age, 41 years; median CD4 cells, 172/microL; histology, diffuse large B-cell lymphoma (n = 42), immunoblastic (n = 2), Burkitt lymphoma (n = 16), and plasmablastic (n = 1); 42 patients with stage III to IV; International Prognostic Index 0 to 1 (n=31), and 2 to 3 (n = 27). Grade 3 or 4 toxicity consisted of febrile neutropenia in nine patients, anemia in 16 patients, and thrombocytopenia in five patients. Complete remission (CR) or unconfirmed CR was achieved in 40 of the 52 assessable patients, partial remission was achieved in five patients, and seven patients experienced progression. Forty-three patients were alive after a median follow-up of 33 months. The estimated 2-year overall survival rate was 75% (95% CI, 64% to 86%). Eighteen patients died: 16 as a result of lymphoma, one as a result of infection, and one as a result of encephalitis.Rituximab adjunction to CHOP produced a CR rate of 77% and a 2-year survival rate of 75% in patients with AIDS-related non-Hodgkin's lymphoma, without increasing the risk of life-threatening infections.
<i>Ralstonia mannitolilytica</i>and COPD: a case report
Authors: Z.Y. Zong, C.H. Peng
Journal: European Respiratory Journal (2011)

To the Editors:

Ralstonia mannitolilytica is a recently established species of clinical significance and was previously known as Pseudomonas thomasii or Ralstonia pickettii biovar 3/ thomasii [1]. It has been recovered from the respiratory tract of patients with cystic fibrosis and has also been associated with catheter-associated bacteraemia, recurrent meningitis, infection of a haemoperitoneum, urinary tract infection and post-renal transplant infection. Hospital outbreaks of R. mannitolilytica due to contamination of water [2], saline solutions [3] or oxygen-delivery devices [4] have also been reported. However, this bacterium has not been reported in patients with respiratory illnesses other than cystic fibrosis.

Isolate G100 was recovered from a sputum sample from a male, 78-yr-old patient in April, 2010. This patient was presented with cough and gradually worsening dyspnoea for 1 month, but without fever. He received no antimicrobial agents prior to admission. This patient had a 20-yr history of intermittent cough, and chronic obstructive pulmonary disease (COPD) was diagnosed 10 yrs previously. He had also had type II diabetes mellitus for 5 yrs and had been a cigarette smoker for >20 yrs, but had stopped smoking 10 yrs previously. Physical examination revealed a “barrel-shaped” chest, reduced breath sounds and crackles. On admission, a full …
Characterization of the defect in activation of factor IX Chapel Hill by human factor XIa.
Authors: K M Braunstein, C M Noyes, M J Griffith, R L Lundblad, H R Roberts
Journal: Journal of Clinical Investigation (1981)

Factor IXChapel Hill (Factor IXCH), an abnormal Factor IX molecule isolated from the plasma of a patient with mild hemophilia B, has previously been shown to exhibit delayed activation by Factor XIa and calcium. In this study, we have found that Factor IXCH is cleaved upon incubation with human Factor XIa and calcium; however, cleavage of this protein is not observed by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis under nonreducing conditions. Under reducing conditions, the rate of disappearance of the zymogen parallels both the appearance of the heavy chain and the generation of clotting activity. In addition, a protein band that migrates with an apparent molecular weight of 45,000 also increases in parallel with clotting activity. Factor IXCH and normal Factor IX (Factor IXN), after incubation with Factor XIa and calcium, were subjected to amino terminal sequence analysis. Activated Factor IXN is cleaved at an arginine-alanine (Arg-Ala) bond and an arginine-valine (Arg-Val) bond as demonstrated by formation of the three amino terminal sequences corresponding to the amino terminal of the light chain, heavy chain, and activation peptide. However, activated Factor IXCH has only two amino terminal sequences, corresponding to the original amino terminal sequence and the heavy chain (formed by cleavage at the Arg-Val bond). It is concluded that the major defect in Factor IXCH is the inability of Factor XIa to cleave the Arg-Ala bond at a significant rate. The rate of formation of clotting activity of Factor IXCH is approximately 60% of the rate of formation of clotting activity of Factor IXN. The specific clotting activity of activated Factor IXCH is between 20 and 33% of activated Factor IXN.
Successful treatment of allergic bronchopulmonary aspergillosis with recombinant anti-IgE antibody
Authors: C. K van der Ent, H. Hoekstra, G. T Rijkers
Journal: Thorax (2007)

Allergic bronchopulmonary aspergillosis (ABPA) can cause severe worsening of the respiratory condition in patients with cystic fibrosis. Treatment can result in steroid dependency and serious adverse events. A dramatic and rapid improvement of respiratory symptoms and lung function after a single dose of anti-IgE antibody (omalizumab) in a 12-year-old girl with cystic fibrosis and ABPA is described. This is the first report of this experimental treatment. It suggests an important role for IgE in the pathogenesis of ABPA and offers new therapeutic possibilities.
Family history of breast cancer
Authors: D Gareth Evans, Douglas Easton
Journal: BMJ (2005)

Family history of breast cancer Referral guidelines changed after acceptance of 10 minute consultationEditor-In their 10 minute consultation on family history of breast cancer Lucassen and Watson drew attention to the recently published guidelines from the National Institute for Clinical Excellence (NICE) on familial breast cancer. 1 2 It is unfortunate that the referral criteria were changed between the acceptance of this article in December 2003 and the final published guidelines in June 2004, which would result in the referral of the patient highlighted in the article for potential mammography screening, rather than for her reassurance.Women aged 40-49 years at moderate risk of breast cancer are entitled to annual mammograms. 2 The definition of moderate risk was based on a risk of at least 3% over the 10 year period from the age of 40 to 50.Available evidence, particularly from combined analyses of case-control studies of familial risks, 3 indicates that a woman reaches this category with a first degree relative (mother or sister) with breast cancer when younger than 40 years or two relatives on the same side of the family (one first degree and one second degree or two first degree) diagnosed at any age.The latter category differs from the draft NICE guidelines and previous referral criteria, which required that the two relatives be diagnosed at an average age of less than 60. 4 This age restriction was removed because it could not be justified on the basis of the available data.It should be noted, however, that referral on the basis of two elderly close relatives is likely to be restricted to the age groups of 30-49, with referral of only high risk groups (for example, two affected relatives diagnosed at an average age of less than 50 years) outside this age group.