tbuckley/cabot-search huggingface dataset:
Feasibility and toxicity of intraperitoneal cisplatin-paclitaxel chemotherapy (IPC) for epithelial ovarian cancer (EOC) in a routine clinical setting
Authors: S. Braun, A. G. Zeimet, L. Hefler, E. Weissenboeck, S. Kickmaier, B. Volgger, A. Reinthaller, C. Marth
Journal: Journal of Clinical Oncology (2008)

16530 Background: We report first clinical experience on routine IPC application: data from the “Austrian Registry on Intraperitoneal Chemotherapy”, a national AGO16 documentation study. Methods: We provide a descriptive intention-to-treat analysis of 33 pts with stage I-III EOC (R<1cm) and IP port implantation. We treated pts with 135–175 mg/m2 paclitaxel/3h IV (d1), 100 mg/m2 cisplatin IP (d2) and 60 mg/m2 paclitaxel IP (d8) (q21d). We registered SAEs and CTCAEs grade 3/4 (abbreviated as S/C) according to GCP criteria. Results: Of 33 pts with implanted IP port, 29 pts actually received a total of 110 (68%) complete cycles (d1,2,8) of 162 scheduled cycles. d8 had to be omitted in 9 pts in up to 4 cycles (median, 1), and a total of 43 cycles were switched to IV paclitaxel(175 mg/m2)-carboplatin(AUC5). Thus, 10 (35%) of 29 pts received complete IPC treatment as planned. In 4 of 33 cases no IPC was administered due to port leakage prior to treatment initiation, α1-antitrypsin deficiency with excess SGOT/SGPT, renal insufficiency from general vasosclerosis, and withdrawal of patient consent. Of the remaining 29 pts with IPC treatment, 4 pts completed all planned cycles without any S/C. In 25 of 29 pts, we registered a total of 107 S/C (3.7/pt). Most frequent S/Cs were: neutropenia (N=29), anemia (N=17), ileus (N=11), subileus (N=9), port leakages/infections (N=8), thrombosis/embolism (N=7), fatigue (N=7), vaginal cuff dehiscence (N=3), septicemia (N=3). Conclusions: Rate of completed full IPC cycles (68%) is improved over published data (42%; Armstrong et al NEJM 2006), and rate of S/Cs was similar (3.7/pt vs. 3.6/pt, respectively). We therefore conclude that IPC can be safely and successfully administered in a routine clinical setting of academic cancer centers. The applied IPC regimen justifies G-CSF prophylaxis of febrile neutropenia, and both careful port management and adequate thrombosis prophylaxis emerged as important clinical issues from our documentation trial. Thus, the national registry serves as a quality assessment and forensic tool that enables both rapid augmentation of clinical data and guided implementation of a new national standard-of-care therapy for EOC pts. No significant financial relationships to disclose.
Efficacy of rituximab in patients with connective tissue disease associated interstitial lung disease: Preliminary results in safety and clinical response
Authors: Julio Gómez-Seco, María Jesús Rodríguez-Nieto, Fredeswinda Romero-Bueno, Sheila Recuero-Díaz, Teresa Presa-Abos, Olga Sánchez-Pernaute, Felipe Villar-Álvarez, Itziar Fernández-Ormaechea
Journal: European Respiratory Journal (2012)

Objectives:  We present safety and clinical outcomes of Rituximab (RTX) in connective tissue diseases-associated interstitial lung disease (CTD-ILD) in a real-life clinical setting.   Methods:  Efficacy was assessed by lung function tests (LFT) and high-resolution computed tomography (HRCT). ILD exacerbations and safety were assessed.   Results:  14 patients with CTD-ILD (29% rheumatoid arthritis, 21% Sjogren, 21% unclassifiable CTD, 14% systemic sclerosis and 14% myopathies) received 4000mg (2000 – 6000) RTX (observation period 161 patient-year). ILD patterns were: 57% usual interstitial pneumonia, 21% unclassifiable ILD, 7% nonspecific interstitial pneumonia, 7% cryptogenic organizing pneumonia and 7% lymphoid interstitial pneumonia. At baseline, IgG levels and leukocyte subset counts were within normal range, with reduced numbers of unswitched memory B cells. Incidence infection rate during RTX therapy was 4.35/100 patient-month (p/m) with one case severe. There was 1 death, due to neutropenia with a disseminated fungal infection. LFT available in 12 patients showed an overall improvement in FVC (85%±19 vs. 73%±18) and DLCO (58%±18 vs. 45%±19). Radiographic progression could be evaluated in 6 patients, with 5 stabilized and 1 improved. ILD incidence relapse rate during RTX therapy was 0.745/100 p/m compared to 5.56/100 p/m in the pre-treatment period.   Conclusions:  Our preliminary data indicate that RTX is safe and shows a low exacerbation rate. Although optimal outcome measures in the short term are difficult to establish, we could confirm disease stabilization in most patients.
Cancer Risk and Low-Penetrance Susceptibility Genes in Gene-Environment Interactions
Authors: Peter G. Shields, Curtis C. Harris
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To provide a concise review for human cancer risk related to low-penetrance genes and their effects on environmental carcinogen exposure. METHODS: Citation of relevant and recent references for molecular epidemiology, focusing on lung cancer, ethical issues, and some clinical implications of recent molecular epidemiology studies. RESULTS: Low-penetrance genes contribute to cancer risk by augmenting the effects of carcinogen exposures. These exposures can be measured in the body through molecular dosimetry (ie, the amount of DNA damage), which reflects a biologically effective dose. The examination of tumors and the mutations within tumor suppressor genes, such as p53, can provide etiologic clues for both exposure and susceptibility. Although many studies have focused on carcinogen metabolism and cancer risk, more recent studies are considering DNA repair. Also, we are learning that behavior, such as tobacco addiction, also may be genetically controlled. CONCLUSION: Sporadic cancers are caused by gene n -environment n interactions rather than a dominant effect by a specific gene, environmental exposure, or gene-environment interaction. New paradigms, where we categorize genes as caretaker or gatekeeper genes, will allow for new hypotheses to be tested and will require advanced methods of analysis. The goal of molecular epidemiology is to develop risk assessment models for individuals, but currently the most achievable goal will be population risk assessment and a better understanding of carcinogenesis.
Impact of food intake on pharmacokinetics(PK) of first-line tuberculosis drugs in treatment-naive patients
Authors: Antonia M. Saktiawati, Marieke G.G. Sturkenboom, Sumardi, Yanri W. Subronto, J.G.W. Kosterink, Ymkje Stienstra, Jan Willem C. Alffenaar, Tjip S. van der Werf
Journal: European Respiratory Journal (2014)

Background :In treatment naive TB patients,the impact of food intake on the PK data of 1st line TB drugs is unknown in the early phase of treatment. Objectives :To assess impact of food intake on PK of isoniazid(INH), Rifampisin(RIF),pyrazinamide(PZA)and ethambutol(EMB) in treatment-naive TB patients. Methods :Randomized,cross-over trial in 20 patients.Subjects were administered INH,RIF,and EMB iv and PZA orally on day 1,and Fixed Drug Combination of all four on day 2&3 either while fasting or along with a high carbohydrate meal.Full PK curves were collected,and assayed by Liquid Chromatography-tandem Mass Spectrometry. Results :mean age was 41.8(SD=20)yrs,mean body mass index 17.48(SD=2.6)kg/m2.The PK data was shown in

View this table:

PK data





Conclusions :In treatment naive TB patients,concomitant food intake substantially influenced PK of TB drugs.Area under the curve(AUC0-24,),maximum concentration(Cmax ) and bioavailability decreased significantly when drugs were taken with food.The impact of the differences found in drug exposure on treatment efficacy and tolerability should be evaluated in a randomized prospective study.
Functional imaging using computational fluid dynamics to assess effect of stimulation of the hypoglossal nerve on upper airway morphology: A pilot study
Authors: Jan De Backer, Wim Vos, Quan Ni, Olivier Vanderveken, Paul Parizel, Paul Van De Heyning, Wilfried De Backer
Journal: European Respiratory Journal (2011)

This study assessed the in-vivo effect of stimulation of the hypoglossal nerve on the upper airway morphology using imaging techniques in combination with computational fluid dynamics (CFD) tools. In 8 patients the upper airway was imaged using CT before and during stimulation of the hypoglossal nerve. Changes in airway volume and resistance were determined using segmentation and CFD. A statistically significant (p = 0.035) enlargement of the volume for the upper airway at the level of the tongue-base was observed. A significant correlation (R2= 0.89, p=0.002) was found between the change in hydraulic radius and the volume changes at the level of the palate. The distance from the tongue base to the mandibula measured just above the epiglottis correlated significantly with the change in upper airway resistance (R2=0.91, p=0.014).  It could be concluded that stimulating the hypoglossal nerve changes the upper airway morphology. A relatively complex motion of the tongue is observed with an enlargement of the airway lumen predominantly near the tongue base. Depending on the volume of the oral cavity, the enlargement is homogeneous or a decrease in cross sectional area occurs at the palatal level. The distance between the tongue base and the mandibula appears to be a good surrogate for changes in upper airway resistance.
Functional variants of 17q12-21 are associated with allergic asthma but not allergic rhinitis
Authors: Anand Kumar Andiappan, Yang Yie Sio, Bernett Lee, Bani Kaur Suri, Sri Anusha Matta, Josephine Lum, Shihui Foo, Geraldine Koh, Jianjun Liu, Francesca Zolezzi, Michael Poidinger, De Yun Wang, Olaf Rotzschke, Fook Tim Chew
Journal: Journal of Allergy and Clinical Immunology (2015)
HSP65-PRA identification of non-tuberculosis mycobacteria from 4892 samples suspicious for mycobacterial infections
Authors: M. Saifi, E. Jabbarzadeh, A.R. Bahrmand, A. Karimi, S. Pourazar, A. Fateh, M. Masoumi, E. Vahidi
Journal: Clinical Microbiology and Infection (2012)
Glutaraldehyde: an occupational hazard in the hospital setting
Authors: F. Di Stefano, S. Siriruttanapruk, J. McCoach, P. Sherwood Burge
Journal: Allergy (1999)

Background: We report a series of 24 health‐care workers with respiratory symptoms suggestive of occupational asthma due to glutaraldehyde exposure. Methods: The history of asthmatic symptoms was investigated with peak expiratory flow rate (PEFR) monitoring, and in eight of the subjects, the specific bronchial provocation test (SBPT) was applied as reference standard for diagnosis of occupational asthma. Levels of glutaraldehyde were monitored in the challenge chamber during the SBPT. Work environmental levels of glutaraldehyde were measured from air samples collected at least once during the PEFR monitoring of endoscopy and theatre nurses. Specific IgE antibodies to glutaraldehyde were measured with a series of glutaraldehyde modified proteins. Results: In the eight workers who underwent SBPT, the diagnosis of occupational asthma was confirmed by a positive reaction (late and dual reaction in five and in three subjects, respectively). The mean level of glutaraldehyde observed during the challenge tests was 0.075 mg/m 3 (range 0.065–0.084 mg/m 3 ). In 13 out of the 16 remaining workers, the serial PEFR monitoring showed a work‐related effect. In three workers, there was no physiological confirmation of occupational asthma. Levels of glutaraldehyde from the air samples collected in the workplace were as follows: personal short‐term samples (mean 0.208 mg/m 3 ; median 0.14 mg/m 3 ; range 0.06–0.84 mg/m 3 ), personal long‐term samples (mean 0.071 mg/m 3 ; median 0.07 mg/m 3 ; range 0.003–0.28 mg/m 3 ). Measurements of specific IgE antibodies to glutaraldehyde‐modified proteins were positive in seven patients (29.1%) according to a cutoff value of 0.88% RAST binding. The presence of atopy to common environmental allergens and smoking was not associated with specific IgE positivity ( P &gt;0.05; Fisher's exact test). Conclusions: Our report indicates the importance of glutaraldehyde as an occupational hazard among exposed health‐care workers. Intervention in the workplace, training of personnel handling this chemical, and accurate health surveillance may reduce the risk of developing occupational asthma due to glutaraldehyde.
A Patient With Anaplastic Lymphoma Kinase–Positive Non–Small Cell Lung Cancer With Development of Leptomeningeal Carcinomatosis While on Targeted Treatment With Crizotinib
Authors: Jonathan W. Riess, Seema Nagpal, Joel W. Neal, Heather A. Wakelee
Journal: Journal of the National Comprehensive Cancer Network (2013)

Leptomeningeal carcinomatosis (LM) is an infrequent yet morbid and often fatal complication of non–small cell lung cancer (NSCLC). Management of LM is multimodal, often involving systemic chemotherapy, radiotherapy, and a variety of symptom management maneuvers to address elevated intracranial pressure, pain, and mood changes that can accompany the disease. It is increasingly recognized that tumors with actionable mutations in NSCLC, including epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) translocations, respond well to systemic therapy with tyrosine kinase inhibitors yet often progress in the central nervous system. More information is needed regarding the natural history and optimal management of LM in specific molecular subtypes of NSCLC. This case report summarizes the management of a patient with ALK-positive NSCLC who developed LM while on targeted treatment with crizotinib within the context of current NCCN Clinical Practice Guidelines in Oncology and recently published studies.
Urinary antigen of S. pneumoniae in the microbiological diagnosis of lower respiratory tract infections
Authors: Sindy Cedeño de Jesús, José Gutierrez Fernandez, Antonio Sorlózano
Journal: European Respiratory Journal (2013)

Background and objective:  The rapid immunochromatographic test for detection of Streptococcus pneumoniae antigen in urine has experienced a request increasing to clinical microbiology laboratories. We compared with conventional microbiological isolation methods and evaluated the impact of the application of this test in the etiological diagnosis in lower respiratory tract infections.  Patients and method:  Six hundred and sixteen determinations were retrospectively studied, whom BinaxNOW® urinary antigen S. pneumoniae was performed. All patients over 14 years old, admitted to the Virgen de las Nieves University Hospital (Granada, Spain) from November 2010, were selected. All patients were divided into two groups: lower respiratory tract infection (LRTI) and no lower respiratory tract infection (No LRTI).  Results:  The diagnosis of LRTI was based on clinical, radiological and/or analytical criteria (529 cases). Of the 616 antigenurias, only 8.6% were positive. In 7/163 sputum cultures the S. pneumoniae was isolated (5 positive antigenurias), 3/152 blood cultures (3 positive antigenurias), 1/10 BAL. In 39% of cases no additional microbiological tests were carried out. On the other hand, 22.5% of 662 samples had a microbiological etiology. The contribution of the antigenuria at the etiologic diagnosis was a 6%, being more frequently positive in pneumonia (39/288). In COPD patients, only three cases had evidence of active pneumococcal infection through antigenuria.  Conclusions:  This technique should be carefully interpreted, especially those with severe infections, as well as, be used in a complementary manner and not in substitution of other microbiological tests.
Widespread Scaly Eruption in a Patient With Multiple Comorbidities
Authors: Elizabeth K. Jones, Nina Mingioni, Jason B. Lee
Journal: JAMA (2015)

A 73-year-old African Americanwoman presented with a widespread scaly pruritic rash lasting 2 months. Her medical history included hypertension, diabetes, pulmonary sarcoidosis, and acid reflux, for which she takes amlodipine, carvedilol, repaglinide, hydroxychloroquine, and pantoprazole. Her history also included chronic renal insufficiency and chronic hepatitis C, for which she takes no medications. She reported no fevers, new skin exposures, oral ulcers, arthritis, alopecia, or photosensitivity and no worsening pulmonary symptoms of cough or shortness of breath. The rash did not improve after 2 weeks of applying topical triamcinolone ointment (0.1%). Physical examination revealed annular coalescing scaly patches with erythematous borders on her forehead, neck, back, and upper and lower extremities (Figure, panels A and B). Laboratory workup revealed an antinuclear antibodies titer of 1:80 with a speckled pattern, elevated Sjogren syndrome–related antigen A (SS-A) level (>8 AI), and no elevation of Sjogren syndrome–related antigen B (SS-B), ribonucleoprotein, double-stranded DNA, Smith, or anti-histone antibodies. Complete blood cell count, erythrocyte sedimentation rate, and C-reactive protein level were within normal limits. Creatinine level was elevated but stable at 1.8 mg/dL (159.1 μmol/L). Skin biopsy revealed an inflammatory pattern of vacuolar interface dermatitis (Figure, panel C). Quiz at jama.com A B
MUC1 gene polymorphisms are associated with serum KL-6 levels and pulmonary dysfunction in pulmonary alveolar proteinosis
Authors: Shinichiro Ohshimo, Nobuhisa Ishikawa, Yasushi Horimasu, Kazunori Fujitaka, Yoshinori Haruta, Hiroshi Murai, Nobuyuki Hirohashi, Noboru Hattori, Koichi Tanigawa, Nobuoki Kohno, Francesco Bonella, Josune Guzman, Ulrich Costabel
Journal: European Respiratory Journal (2013)

BACKGROUDS:  KL-6, a human MUC1 mucin, is a sensitive biomarker for interstitial lung diseases including pulmonary alveolar proteinosis (PAP). Recent studies have demonstrated a correlation between MUC1 gene single nucleotide polymorphisms (SNPs) and serum KL-6 levels.   AIMS:  To investigate the correlations between serum KL-6 levels, pulmonary dysfunction and MUC1 SNPs in PAP.   METHODS:  24 Caucasian patients with PAP and 30 healthy Caucasian were prospectively collected. Serum KL-6 levels were analyzed using ELISA and MUC1 rs4072037 SNPs were genotyped using polymerase chain reaction. The correlation between serum KL-6 levels, pulmonary dysfunction and MUC1 SNPs were evaluated.   RESULTS:  The frequency of MUC1 rs4072037 SNPs was significantly different between PAP patients and healthy volunteers (PAP, A/A 46%, A/G 54%, G/G 0%; healthy, A/A 30%, A/G 40%, G/G 30%; p=0.013). Serum KL-6 levels in PAP patients were significantly higher than in healthy volunteers (p 2  at rest, total lung capacity, diffusing capacity for carbon monoxide (D LCO ) and time to next whole lung lavage (p=0.002, p=0.036, p=0.038, p=0.028 and p=0.018, respectively). MUC1 A/G genotype was associated with decreased alveolar-arterial oxygen difference (A-aDO 2 ) and increased D LCO  compared with A/A genotype (p=0.022, p=0.044, respectively).   CONCLUSIONS:  MUC1 rs4072037 SNPs were correlated with serum KL-6 levels and the severity of pulmonary dysfunction in PAP.
Immunoproteasome expression in pulmonary fibrosis
Authors: Ilona Keller, Angela Dann, Isis Fernandez-Buelvaz, Shinji Takenaka, Andreas Günther, Oliver Eickelberg, Silke Meiners
Journal: European Respiratory Journal (2013)

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with unknown cause ultimately leading to death. It is believed that repetitive microinjuries of the alveolar epithelial cells initiate chronic wound healing and immune responses which ultimately leads to pulmonary fibrosis. Immunomodulatory cytokines such as IFNγ and IL17 contribute to disease pathogenesis. Only recently, the IFNγ inducible immunosubunits of the proteasome have been shown to affect regulation of adaptive immune responses. Here, we investigated the expression pattern and possible involvement of immunoproteasomes (IP) in pulmonary fibrosis.  To study regulation of IP in lung cells in vitro, we analyzed expression of IP subunits LMP2 and LMP7 in different cell lines and primary mouse and human lung fibroblasts. IFNγ induced pronounced expression of IP in all examined cell types. Expression levels of LMP2 and LMP7 were evaluated in wildtype (wt) as well as LMP2-/- and LMP7-/- mice in whole lung homogenate. Of note, we observed pronounced expression of IP subunits in wt lungs compared to other organs. Expression of IP was induced in bleomycin-induced pulmonary fibrosis and remained elevated even during tissue repair. Notably, immunohistochemical analysis of lung sections of human donor (n=6) or IPF patients (n=7) revealed expression of LMP2 in alveolar macrophages and interstitial cells in both donor and IPF. LMP2 positive alveolar epithelial cells, however, were only detected in IPF lungs. We are currently investigating the causal role of LMP2 in pulmonary fibrosis using LMP2 deficient mice.  Elevated levels of IPs in pulmonary fibrosis might add to disease course by affecting adaptive immune responses in the lung.
Emergence of carbapenem-resistant Enterobacteriaceae in Austria, 2001–2010
Authors: G. Zarfel, M. Hoenigl, B. Würstl, E. Leitner, H.J.F. Salzer, T. Valentin, J. Posch, R. Krause, A.J. Grisold
Journal: Clinical Microbiology and Infection (2011)
Effect of aminophylline and verapamil upon diaphragmatic force generation in dogs
Authors: EL De Vito, AJ Roncoroni
Journal: European Respiratory Journal (1990)

The effects on the diaphragm of verapamil (VPM) and aminophylline (AMP) were studied in dogs during stimulation of phrenic nerves at the 5th cervical roots (5th-PS) or transvenously at the trunk (T-PS). Transdiaphragmatic pressure (Pdi)/frequency curves were constructed. Our findings were: 1) AMP increased Pdi at all stimulation frequencies (p less than 0.01) during 5th-PS but only at 10-30 Hz during T-PS; 2) in other dogs infusion of VPM (0.14 mg.kg-1.min-1) decreased Pdi at all frequencies (p less than 0.025) without change in diaphragmatic blood flow; 3) the effects of VPM were completely reverted by AMP; 4) after a large amount of AMP, infusion of VPM (0.21 mg.kg-1.min-1) decreased Pdi at all frequencies. Since these drugs have several mechanisms of action and do not show mutual blocking effect, different action sites are suggested.
Detection of metastatic neuroblastoma in bone marrow: when is routine marrow histology insensitive?
Authors: N K Cheung, G Heller, B H Kushner, C Liu, I Y Cheung
Journal: Journal of Clinical Oncology (1997)

PURPOSE To measure the sensitivity of histologic examination in detecting metastatic solid tumor in bone marrow. PATIENTS AND METHODS A total of 145 patients with stage 4 neuroblastoma underwent 840 marrow examinations, each consisting of six sites (four aspirates and two biopsies), from October 1990 to June 1996 at Memorial Sloan-Kettering Cancer Center. Metastasis was detected by either histology (aspirate by Wright-Giemse and biopsy by Hematoxylin-Eosin stains) or immunostaining of aspirates using anti-G(D2) monoclonal antibodies. RESULTS The absence of tumor by histology at a single marrow site was a poor guarantee of the absence of disease. The number of false-negative sites increased as the percent of G(D2)-positive tumor cells in the marrow decreased: zero of six if tumor cell count was &gt; or = 1%, and approximately six of six sites if &lt; or = 0.003%. Sensitivity was comparable between marrow aspirate and biopsy. A lower bound (LB) for the probability of false-negative histology was calculated from the (1) discordance among the six marrow samplings and (2) comparison with immunofluorescence. When disease was extensive (eg, at diagnosis), the LB was 0.13 and 0.3, respectively. After treatment, it increased to 0.37 and 0.8. Examining multiple marrow sites can decrease the LB to 0.15. However, at least three sites have to be negative at relapse, six at diagnosis, and more than 50 during treatment or off-therapy follow-up. The marginal decrease in the LB by additional samplings rapidly diminished to less than 0.05 after two sites. CONCLUSION Except at diagnosis and relapse when gross disease is present, marrow sampling by histology has limited sensitivity. Current practice grossly underestimates the true prevalence of marrow disease.