tbuckley/cabot-search huggingface dataset:
Non-tuberculous mycobacterium infection in lung transplant recipients
Authors: Héctor Eduardo Riera Ave, Carles Bravo, Berta Sáez, Teresa Tórtola, Fernando Ruiz, Cristina Berastegui, Manuel Lopez Meseguer, Victor Monforte, Antonio Román
Journal: European Respiratory Journal (2014)

BACKGROUND: Non-tuberculous mycobacterial (NTM) infections are relatively frequent in lung transplant (LT) recipients and they might be associated with increased morbi-mortality.  METHODS: We did a retrospective and observational review of LT recipients from whom NTM were isolated between 2002 and 2013 (n=539) that had at least one NTM positive culture, to study the incidence, clinical manifestations, treatment and outcome  RESULTS: 25 patients had NTM positive cultures. 72% were men, the mean age was 46.75 years (r 7-63). 72% were bilateral LT recipients  Most frequent culture sources were tracheal aspirate, sputum, bronchoalveolar lavage. 44% had positive perioperative cultures (2 of the donor and 9 of the recipient), 56% were diagnosed during follow up, with a mean of 283.92 days post LT (r 20-1291). 3 patients had NTM infection prior to the LT.  56% patients developed NTM disease and were treated. Most frequent symptoms were cough, bronchorrea and dyspnea. 6 patients developed NTM extrapulmonary disease. Most frequent radiologic findings were pulmonary nodules, consolidations, and ground glass opacities.  The most frequent NTM were M. abscessus 24%, M. gordonae 20%, M. fortuitum 12%, M. immunogenum 12%. 1 presented concomitant M. avium and M. tuberculosis infection. 28% patients that had NTM infection died, mean of 670,14 days post LT (r 55-2173), 1 of them by disseminated M. abscessus disease  CONCLUSIONS: Incidence of NTM infection among LT recipients in our center between 2002-2013 is 4,63% (disease 2,59% , colonization 2,04%)  The most frequent NTM were M. abscessus, M. gordonae, M. fortuitum.  NTM infection prior to the LT increases the risk of NTM infection post LT  1 of the deaths was linked directly to NTM.
A phase I dose escalation study of oral bexarotene in combination with intravenous decitabine in patients with AML
Authors: John S. Welch, Haixia Niu, Geoffrey L. Uy, Peter Westervelt, Camille N. Abboud, Ravi Vij, Keith E. Stockerl‐Goldstein, Meagan Jacoby, Iskra Pusic, Mark A. Schroeder, John F. Dipersio, Amanda F. Cashen
Journal: American Journal of Hematology (2014)

The response rate of non-M3 acute myeloid leukemia (AML) to all trans retinoic acid has been limited. Using Affymetrix expression arrays, we found that in diverse AML blasts RXRA was expressed at higher levels than RARA and that mouse Ctsg-PML-RARA leukemia responded to bexarotene, a ligand for RXRA. We therefore performed a phase I study of combination bexarotene and decitabine in elderly and relapsed AML patients. We found that this combination was well tolerated, although outcomes were modest (1 CRi, and 3 PR among 19 patients). Correlative studies found that patients with clinical response had increased differentiation to bexarotene both in vivo and ex vivo, suggesting that pre-treatment analysis might identify a more susceptible subgroup of patients.
Histogenetic Behavior of Tumors. I. Morphologic Variation &lt;italic&gt;In Vitro&lt;/italic&gt; and &lt;italic&gt;In Vivo&lt;/italic&gt; of Two Related Human Carcinoma Cell Lines&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Nelly Auersperg
Journal: JNCI Journal of the National Cancer Institute (1969)

The histogenetic behavior of two human cervical squamous carcinoma cell lines (C-4 I and C-4 II), originating from the same biopsy specimen and probably from the same cell clone, were examined histochemically and electron microscopically in vitro and in vivo. In culture, C-4 I cells formed compact, highly stratified, epithelial colonies, flattened on contact with culture medium, and retracted from substrata in response to crowding. In culture, C-4 II cells formed spreading, predominantly monolayered, epithelial colonies with hemicysts, joined by junctional complexes on contact with culture medium, and segregated in response to crowding. When inoculated into hamster cheek pouches, C-4 I cells grew as expanding, compact masses, whereas C-4 II cells in small groups infiltrated connective tissues. Thus the in vitro growth patterns of the cell lines were reproduced in the patterns of invasion in vivo. Glycogen was produced in vivo by C-4 I cells only, and basement membranes were found around tumors of both cell lines. The morphologic and functional characteristics of the cell lines could be interpreted as due partly to the retention of tissue-specific properties of normal epithelial cells at various levels of squamous differentiation.
Comparative Study of Interstitial Cell Tumors of Rat Testis Induced by Cadmium Injection and Vascular Ligation&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Samuel A. Gunn, Thelma Clark Gould, W. A. D. Anderson
Journal: JNCI Journal of the National Cancer Institute (1965)

A single subcutaneous injection of cadmium salts caused selective acute injury to the vasculature of the rat testis, the internal spermatic artery and its branches, and the pampiniform plexus, leaving untouched the deferential (vasal) vessels accompanying the vas deferens. Total necrosis resulted, but interstitial tissue in time regenerated and resulted in interstitial cell tumor (ICT) formation. ICT also occurred in rats after ligation of the blood vessels of the testis, the internal spermatic artery, and pampiniform plexus, either alone or in combination with ligation of the vas deferens and vasal vessels. Since cadmium injury produces, in a sense, a “selective chemical ligation” of the testicular vasculature, a comparison was made between the ICT resulting from total vascular ligation (spermatic plus vasal vessels), partial vascular ligation (spermatic vessels only), and cadmium injection. The incidence of ICT formation varied from 68 to 91 percent 1 year after surgical vascular ligation or cadmium injection; there was no significant difference between the various tumor-induction methods with regard to the incidence of ICT. Although by routine staining methods the ICT's formed by the three tumor-induction methods studied were indistinguishable morphologically, they did exhibit different endocrine characteristics. Androgenic activity, as indicated by the capacity of the dorsolateral prostate to take up Zn65, was significantly lower in rats with total vascular ligation than in rats with partial vascular ligation or cadmium injection. In all experimental groups, the androgenic activity was significantly lower than in intact controls. Although zinc was known to prevent the formation of ICT induced by cadmium, it did not alter the development of ICT induced by either partial or total vascular ligation.
Quantification of elastin fibre remodelling in COPD using probe-based confocal laser endomicroscopy (pCLE)
Authors: Michael Bennett, John Fleming, Tom Havelock, Joy Conway, Peter Howarth
Journal: European Respiratory Journal (2012)

COPD causes disruption of alveolar elastin and probable disruption of the elastin in the airway wall. pCLE can be used during bronchoscopy to image the elastin structure. A method for the automatic assessment of the directional distribution of the elastin fibres is presented. The structural disorder caused by the remodelling process can then be objectively quantified. Figure 1 shows examples of the analysis output, with detected elastin fibres in green, showing greater disorder in the case of mild COPD.

![Figure][1] 



Figure 2 shows example histograms of the direction of the elastin fibres, showing a clear broadening of the histogram between health and COPD.

![Figure][1] 



Initial results from 8 subjects, 4 healthy and 4 mild COPD (Table 1) demonstrate the difference is significant (independent t-test, p=0.0363).

View this table:



These initial results suggest that this technique has potential as an objective, in vivo measure of elastin remodelling in the airways.

 [1]: pending:yes
Lactate dehydrogenase-B cDNA from the teleost Fundulus heteroclitus: evolutionary implications.
Authors: D L Crawford, H R Constantino, D A Powers
Journal: Molecular Biology and Evolution (1989)

A cDNA that encodes the heart-type lactate dehydrogenase (LDH-B) from the teleost fish Fundulus heteroclitus was cloned and sequenced. The protein encoded by the cDNA was analyzed in relation to 13 LDH proteins from a variety of taxa. One of the deductions from this analysis is that LDH-B proteins have residues in the active site that are unique and that may be important in determining the biochemistry of the heart-type isozyme. Phylogenetic analysis of the LDH sequences indicates that the branch lengths are greater in lower vertebrates, suggesting that the amino acid replacement rates vary depending on the evolutionary constraints within each taxon. Furthermore, the analysis suggests that LDH-C arose prior to the divergence of the LDH-A and LDH-B isozymes and thus that it is probably ancestral to these isozymes.
Functional exercise capacity, lung functions, and muscle strength in allogeneic hematopoietic stem cell transplantation recipients suffering from graft versus host disease
Authors: Meral Bosnak Guclu, Gulsah Bargi, Zeynep Aribas, Burcu Camcioglu, Muserrefe Nur Karadalli, Zeynep Sahika Aki, Nurdan Kokturk, Muge Aydogdu, Gulsan Türkoz Sucak
Journal: European Respiratory Journal (2013)

Background:  Graft versus host disease (GVHD) is one of the major complications of allogeneic hematopoietic stem cell transplantation (HSCT) and is a reaction of donor immune cells against host tissues. Reduced exercise capacity, lung function abnormalities and muscle weakness are frequently seen during the treatment process. However, no study investigated the impact of GVHD in allogeneic HSCT recipients.   Aim : To compare functional exercise capacity and pulmonary functions, carbon monoxide diffusing capacity (DLCO), respiratory and peripheral muscle strength in allogeneic HSCT recipients with and without GVHD.   Methods : Ten patients (40.10±15.64 years) with and 28 patients (38.75±12.05 years) without GVHD, allogeneic HSCT recipients were included. Pulmonary functions and DLCO were measured. Functional exercise capacity was evaluated using 6-minute walk test (6MWT), respiratory muscle strength (MIP, MEP) using mouth pressure device, quadriceps femoris (QF) and hand grip (HG) muscles strength using dynamometer.   Results:  Six-MWT distance (p=0.001), FEV 1 % (p=0.005), FVC% (p=0.004), PEF% (p=0.016), FEF 25-75%  (p=0.018) ,  DLCO% (p=0.009), MIP (p=0.07), QF (p=0.017) and HG muscle (p=0.021) strength were significantly lower in recipients suffering from GVHD compared to recipients without GVHD.   Conclusions:  Graft versus host disease additionally reduces functional exercise capacity, pulmonary functions, diffusion capacity, respiratory and peripheral muscle strength. Studies are needed to investigate the effects of inspiratory, peripheral muscle and aerobic exercise training in allogeneic HSCT recipients suffering from GVHD.
Pharmacokinetic, oral bioavailability, and safety study of fluorouracil in patients treated with 776C85, an inactivator of dihydropyrimidine dehydrogenase.
Authors: S D Baker, S P Khor, A A Adjei, M Doucette, T Spector, R C Donehower, L B Grochow, S E Sartorius, D A Noe, J A Hohneker, E K Rowinsky
Journal: Journal of Clinical Oncology (1996)

PURPOSE To study the absolute bioavailability and pharmacokinetics of an oral solution of fluorouracil (5-FU) in patients treated with 776C85, an oral inactivator of dihydropyrimidine dehydrogenase (DPD), and to evaluate the feasibility of administering oral 5-FU and 776C85 on a multiple-daily dosing schedule. PATIENTS AND METHODS Twelve patients with refractory solid tumors were enrolled onto this three-period study. In periods 1 and 2, patients were randomly assigned to treatment with 5-FU 10 mg/m2 on day 2 given by either the oral or intravenous (IV) route with oral 776C85 3.7 mg/m2/d on days 1 and 2. In period 3, patients received escalating doses of 5-FU (10 to 25 mg/ m2/d) orally for 5 days (days 2 to 6) with 776C85 3.7 mg/m2/d orally (days 1 to 7) every 4 weeks. Pharmaco-kinetic studies were performed in periods 1 and 2, and after the fifth oral dose of 5-FU in period 3. RESULTS Twelve patients completed the bioavailability and pharmacokinetic studies. Following oral 5-FU 10 mg/m2, the bioavailability was 122% +/- 40% (mean +/- SD), the terminal half-life (t1/2 beta) was 4.5 +/- 1.6 hours, the apparent volume of distribution (V beta) was 21.4 +/- 5.9 L/ m2, and the systemic clearance (Clsys) was 57.6 +/- 16.4 mL/min/m2. A correlation was observed between oral 5-FU systemic clearance and calculated creatinine clearance (r = .74; P = .009). Multiple-daily dosing did not appear to affect the pharmacokinetics of oral 5-FU. Neutropenia was the principal toxicity of oral 5-FU and 776C85, precluding escalation of oral 5-FU to doses greater than 25 mg/m2/d for 5 days every 4 weeks with 776C85. CONCLUSION The oral DPD inactivator 776C85 enables oral administration of 5-FU and may alter conventional 5-FU administration practices.
Results of the Sixth International Society of Pediatric Oncology Wilms' Tumor Trial and Study: a risk-adapted therapeutic approach in Wilms' tumor.
Authors: M F Tournade, C Com-Nougué, P A Voûte, J Lemerle, J de Kraker, J F Delemarre, M Burgers, J L Habrand, C G Moorman, D Bürger
Journal: Journal of Clinical Oncology (1993)

PURPOSE The Sixth International Society of Pediatric Oncology study (SIOP6) concerned Wilms' tumor with favorable histology, preoperatively treated to obtain a high rate of stage I patients, and sought to reduce treatment for patients with stage I and stage II negative nodes (IIN0) tumors and to find better therapy to prevent relapses in stage II positive nodes (IIN1) and stage III patients. PATIENTS AND METHODS Eligible patients (N = 509) had received four weekly doses of vincristine (VCR) and two courses of dactinomycin (AMD) preoperatively and were assigned after surgery, according to stage and lymph node involvement, to three different prognostic groups, which were to be randomized. Stage I patients (n = 303) received VCR and AMD either for 17 weeks (S) or 38 weeks (L). Stage IIN0 patients (n = 123) received either 20 Gy irradiation (R+) or no irradiation (R-) and received VCR and AMD for 38 weeks. Stage IIN1 and III patients (n = 83) received intensified VCR and AMD (INTVCR) versus VCR, AMD, and Adriamycin (ADRIA; Doxorubicin Farmitalia Carbo Erba, Rueil, Malmaison, France; doxorubicin). Assessment criteria were 2-year disease-free survival (DFS) and 5-year survival (SURV) percentages. A stopping rule was added that took into account abdominal recurrences for the stage IIN0 trial. RESULT A 52% rate of stage I tumors was obtained, with a low rate of ruptures (7%). The 2-year DFS and 5-year SURV rates according to the different therapeutic groups were stage I, 92% versus 88% (equivalent) and 95% versus 92% for S and L, respectively; stage IIN0, 72% versus 78% (stage equivalent) and 88% versus 85% for R+ and R-, respectively; and stage IIN1 and stage III, 49% versus 74% (P &lt; .029) and 77% versus 80% for INTVCR and ADRIA, respectively, which results in an 82% DFS and 89% SURV rate for the entire trial population. However, six abdominal metastases observed during the first year of follow-up (FU) in the R- group versus none in the R+ group resulted in discontinuation of the stage IIN0 trial. CONCLUSION Risk-adapted therapy to limit risk of sequelae is possible. More intensive chemotherapy is necessary to prevent abdominal recurrences in nonirradiated stage IIN0 patients treated preoperatively. A three-drug protocol is necessary in stage IIN1 and stage III patients.
The influence of respiratory infection on bronchial asthma
Authors: Dmitry Ruzanov, Nataly Efimova, Elena Davidovskaya, Tatyana Baranovskaya, Irina Buynevich, Nataly Plotnikova, Olga Serdyukova
Journal: European Respiratory Journal (2012)

Acute respiratory infection (ARI) intensify the severity of inflammation reaction of bronchial asthma (BA).  AIM: to study the influence of ARI on the level of the control over BA and the immunology of this combination and the possibilities of treatment.  METHOD: The clinical monitoring over 316 patients with bronchial asthma for a year, the immunological research and the results of treatment with affine purified antibodies for gamma-interferon of the human (48 cases).  RESULTS: during the observation there were fixed 4,1±0,3 episodes of ARI for each patient. Analyzing the graph of frequency of ARI with BA, some differences with seasonal virus ARI attract our attention. There is no traditional apex of seasonal virus ARI in the February, the reduction of tension is seen only by May, summer months are not also free from ARI, and the intensity of winter months the frequency of ARI reaches already in October. There is not direct link between the frequency of ARI and the level of control over asthma. The dependence of the dose of ICS and the frequency of ARI was also detected. On the whole, each patient received 2,7±0,6 the course of antibiotics therapy relatively to respiratory pathology. 94,4% of patients got different mukoactive drugs.  Low tension of the immunity was fixed: CD4/CD8 index was 1,23±0,08, phagocytic index was 62±2,1%. After three month of the use of antibodies for gamma-interferon frequency of ARI was marked, the real improvement of the rate of the cellular immunity, the increase of the level of IgG to 9,88±0,41 l/l with the following return to the previous level, and also the real reduction of the level of IgE to 69,2±5,5 among the patients with exogenous asthma.
Abstract 12461: Cardiopulmonary Exercise Testing in 117 Moderate to Severe Aortic Stenosis Patients; A Prospective, Descriptive Study
Authors: Van D Le, Hanne Elming, Gunnar V Jensen, Steen Carstensen, Lars Kjoller-Hansen
Journal: Circulation (2011)

Background:  We hypothesized that cardiopulmonary exercise testing (CPET) compared to conventional exercise testing (CET) generates more conclusive results and differentiates patients with truly asymptomatic aortic stenosis (AS) from symptomatic AS and functional limitations due to other causes.   Methods:  CET with additional CPET information were performed in 117 patients, median age 72 years (range 44-90), with asymptomatic or questionably symptomatic AS with AVA 3,5m/s.   Results  of CPET were interpreted according to Wassermann algorithm and CET after the international guidelines. An abnormal CPET as peak oxygen uptake (pVO2)    Results:  CPET was conclusive in 115 compared to 89 patients examined by CET (p   Conclusions:  In patients with moderate to severe AS, including older and sedentary persons, CPET is feasible, and compared to CET gives more conclusive results and helps differentiate between patients with truly asymptomatic AS and functional limitations due to AS or other causes.
Evaluation of length, maximum Gleason score, and extension of disease at positive surgical margins during radical prostatectomy.
Authors: Hooman Djaladat, Mehrdad Alemozaffar, Christina Day, Manju Aron, Jie Cai, Tracy Campanelli, Gary Lieskovsky, Siamak Daneshmand
Journal: Journal of Clinical Oncology (2014)

98 Background: Positive surgical margin (PSM) found following radical prostatectomy (RP) is known to affect subsequent recurrence and survival. The extent of PSM has been shown to impact clinical outcomes. We examined the effect of length of PSM, extent of disease at PSM and maximum Gleason score at PSM on oncologic outcomes. Methods: A retrospective review of 3971 patients undergoing RP for prostate cancer at our institution between1978-2009 revealed 1053 patients with PSM, out of whom 814 received no hormone therapy. The initial 175 patients were selected to maximize available follow-up, and their slides were re-reviewed for following parameters: length of PSM (mm), maximum Gleason score at PSM, and maximal extension of PSM (intraprostatic incision vs. extracapsular extension). Data was available in 107 patients who are the subject of this study. Multivariable Cox regression models were used to evaluate the impact of above features as well as age, preoperative PSA, pathologic Gleason score, stage and adjuvant radiotherapy on biochemical and clinical recurrence-free survival (RFS), and overall survival (OS). Results: Median follow-up was 17.6 years. Maximum extension of PSM was limited to intraprostatic incision in 63 (58.9%) and extracapsular in 44(41.1%) patients. Median length of PSM was 4 mm (range 1-55 mm); 41 (38.3%) with &lt;3mm and 66 (61.7%) with &gt;4mm. Maximum Gleason score at PSM was &lt;6 in 70 (66.0%) and &gt;7 in 36 (34%) patients. 10-yr PSA RFS, clinical RFS, and OS were 60.2%, 80.7%, and 60.2%, respectively. Multivariable Cox regression modeling showed the length of PSM &gt;4mm and extracapsular extension as independent predictors of PSA RFS and clinical RFS. Age and extracapsular extension were independent predictors of OS. Conclusions: PSM &gt;4mm and extracapsular extension have a higher risk of PSA and clinical recurrence after RP. These findings can help decision-making regarding adjuvant therapy in patients with PSM and should be reported by pathologists in addition to the presence of PSM. [Table: see text]
First-line high-dose chemotherapy ± radiation therapy in patients with metastatic germ-cell cancer and brain metastases
Authors: C. Kollmannsberger, C. Nichols, M. Bamberg, J.T. Hartmann, N. Schleucher, J. Beyer, P. Schöffski, G. Derigs, U. Rüther, I. Böhlke, H.-J. Schmoll, L. Kanz, C. Bokemeyer
Journal: Annals of Oncology (2000)

To examine the feasibility and efficacy of first-line high-dose chemotherapy (HD-CTX) in patients with advanced metastatic germ-cell tumors (GCT) and brain metastases.Twenty-two patients with brain metastases at initial diagnosis were identified within a cohort of two hundred thirty-one consecutive patients with advanced metastatic disease, entered on a German multicenter trial between January 1993 and July 1998. All patients received first-line HD-CTX with cisplatin-etoposide-ifosfamide (HD-VIP) followed by autologous stem-cell transplantation. Brain irradiation (BRT) with 30-50 Gy +/- 10 Gy boost was applied in patients with symptomatic CNS disease or as consolidation in case of residual CNS lesions after HD-CTX.A median number of 4 HD-CTX cycles (range 2-5) were applied to the 22 patients. Ten patients received HD-CTX alone and twelve patients were treated with HD-CTX plus BRT. Median duration of WHO grade 4 granulocytopenia and thrombocytopenia was seven and five days after each cycle, respectively. Non-hematologic toxicity consisted mainly of mucositis/enteritis (WHO grade 3-4 32%). Two early deaths occurred in twenty-two patients (one CNS-bleeding/one sepsis). Fourteen of twenty patients achieved a CR/PRm- status. Twenty patients (91%) responded in the brain (55% CR/36% PR). Two-year progression-free and overall survival rates were 72% and 81%, respectively. These survival rates are substantially higher compared to the available data in the literature.High-dose chemotherapy with autologous stem-cell support +/- BRT appears to be feasible without increased therapy-related mortality in patients with advanced metastatic GCT and brain metastases. The results achieved emphasize the high chemosensitivity of CNS metastases from GCT and suggest a potential role for dose intensification. The dose of BRT in addition to HD-CTX may be tailored to the presence of clinical symptoms and the response of CNS metastases to chemotherapy.