tbuckley/cabot-search huggingface dataset:
Pulmonary hypertension in obesity-hypoventilation-syndrome
Authors: Christoph Kauppert, Iris Dvorak, Johannes Gebauer, Florian Kollert, Frank Heinemann, Michael Pfeifer, Stephan Budweiser
Journal: European Respiratory Journal (2011)

Introduction:  In Obesity-Hypoventilation-Syndrome (OHS), pulmonary hypertension (PH) is considered a common feature.   Aims:  To determine frequency and severity of PH in OHS patients treated with non-invasive pressure ventilation (NPPV).   Methods:  Prospective cross-sectional study of consecutive patients admitted for follow-up of NPPV (initiated ≥3 months before). OHS was defined by BMI≥30kg/m 2 , capillary carbondioxid tension (PaCO 2 )≥45mmHg prior NPPV initiation without other causes for hypoventilation. Right-heart catheterization (RHC) was performed at rest without oxygen supplementation, daytime sleepiness measured by Epworth Sleepiness Scale (ESS).   Results:  177 patients considered to have OHS were screened. Among 64 patients who met the diagnosis criteria for OHS, 21 patients (10f, 11m; median age 62.2 [53.9;71.7] years, BMI 45 [40;53] kg/m 2 , PaCO 2  39.6 [37.8;45.5] mmHg) gave consent for RHC. Only 4 (19%) patients had normal mean pulmonary artery pressure (mPAP 2 /cm 5 ; 8 patients (38.1%) presented with “Borderline”-PH (mPAP 20-24mmHg), mPAP 22 [22.5;23] mmHg and PVRI 392 [287;485] and 9 patients (42.9%) had a manifest PH (mPAP≥25mmHg), mPAP 33 [29;34] mmHg and PVRI 440 [384;728]. In 3 patients with PH, pulmonary capillary wedge pressure was >15mmHg; 2 of them presented with transpulmonary pressure gradient >12mmHg. In patients with PH, ESS (7 [6;11]) was significantly higher than in those without PH (3 [0.5;5.5], p=0.03) or Borderline-PH (3.5 [2.5;6.5], p=0.03).   Conclusion:  Mild to moderate PH is quite frequent in OHS, even after initiation of NPPV. Its impact on survival and quality of life has to be studied in future trials.
Identification of Emergency Department Patients With Acute Heart Failure at Low Risk for 30-Day Adverse Events
Authors: Sean P. Collins, Cathy A. Jenkins, Frank E. Harrell, Dandan Liu, Karen F. Miller, Christopher J. Lindsell, Allen J. Naftilan, John A. McPherson, David J. Maron, Douglas B. Sawyer, Neal L. Weintraub, Gregory J. Fermann, Susan K. Roll, Matthew Sperling, Alan B. Storrow
Journal: JACC Heart Failure (2015)
Abstract 2728: Thermal ablative therapy with novel gold nanorods in an orthotopic model of urinary bladder cancer
Authors: Xiaoping Yang, Lih-Jen Su, Francisco G. La Rosa, Elizabeth Erin Smith, Suehyun Katherine Cho, Brian Kavanagh, Won Park, Thomas W. Flaig
Journal: Cancer Research (2014)

Abstract Background The use of nanoparticles has shown great therapeutic potential, but delivery and clearance concerns have limited their use systemically. Intravesical instillation of nanoparticles in the urinary bladder provides a unique administration route to treat superficial bladder cancer. We examined the anti-tumor effect of epidermal growth factor receptor (EGFR)-directed gold nanorods combined with photothermal treatment in a superficial bladder cancer model. Methods A novel orthotopic nu/nu murine xenograft model was established through intravesical instillation of T24 human bladder cancer cells labeled with Luciferase. After confirmation of positive tumor cell implantation via bioluminescence, gold nanorods linked to the anti-EGFR antibody C225 were instilled into the bladder cavity. The nanorods were specifically fashioned to respond to near infrared (NIR) light, which was externally administered via an 808 nm diode laser to the bladder. A safe and effective regimen of in vivo photothermal ablation was determined by optimizing the duration, power and distance from the tumor to the laser source. The anti-cancer effect was monitored by an in vivo imaging system in a non-invasive manner. Results The tumor implantation rate with the T24 human cancer cell was approximately 90%. The optimized regimen of photothermal treatment in this setting was laser power of 2.1 W/cm2 for 30 seconds at 2.5 centimeters from the skin. Using this in vivo tumor model, and near-infrared energy combined with C225-conjugated gold nanorods, we demonstrate significant therapeutic efficacy against the implanted orthotopic bladder tumor (Table) with minimal systemic toxicity using this regimen. Conclusions Photothermal ablation with EGFR-directed gold nanorods is effective and well tolerated in an in vivo model of urinary bladder cancer. Future clinical development would include NIR light delivery via a cystoscope in a human application Summary of luciferase results of in vivo photothermal treatmentTotal miceLuciferase DecreaseLuciferase IncreaseLuciferase No Significant ChangeConjugated Nano Rods+Laser161303Laser Only14275 Citation Format: Xiaoping Yang, Lih-Jen Su, Francisco G. La Rosa, Elizabeth Erin Smith, Suehyun Katherine Cho, Brian Kavanagh, Won Park, Thomas W. Flaig. Thermal ablative therapy with novel gold nanorods in an orthotopic model of urinary bladder cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2728. doi:10.1158/1538-7445.AM2014-2728
Treatment of advanced homogenous emphysema with endobronchial coils compared to NETT subjects who received LVRS or medical therapy
Authors: Nathaniel Marchetti, Jason Krahnke, Theresa Kaufman, Divay Chandra, Felix Herth, Pallav Shah, Dirk-Jan Slebos, Chandra Dass, Frank Sciurba, Gerard Criner
Journal: European Respiratory Journal (2014)

The National Emphysema Treatment Trial (NETT) demonstrated that LVRS added to maximal medical therapy (MT) was not beneficial in advanced homogenous emphysema leaving only lung transplantation or MT as viable therapeutic options. We hypothesized that bronchoscopic lung reduction using nitinol coils (LVRC) might be more effective than MT alone in patients with advanced homogenous emphysema.  We examined 12-month outcomes in patients with advanced homogenous emphysema (bilateral LVRC vs. NETT subjects), matched by lung function and age. Lung function, survival, QOL and 6-minute walk distance (6MWD) were compared between LVRC, NETT MT and NETT LVRS groups. Data are reported as least squares means with IQR and analyzed using ANOVA.  There were 85 LVRC (46%Men), 51 LVRS (47%Men), and 43 MT (67%Men) subjects with no difference in baseline FEV 1 % predicted (27.6±7.3%, 26.8±3.8%, 27.6±4.3% respectively). TLC (137.9±19.0%, 135.4±8.9%, 136.3±9.3%, p=0.34) was similar but baseline 6MWD (m) was lower in LVRC group (310.8±96.6, 371.4±84.1, 342.3±99.9, pl0.001). 12-month outcomes data (Table 1) shows that LVRC improved hyperinflation, air trapping and 6MWD compared to MT. 12-month survival was 96.4% (LVRC), 78.4% (LVRS) and 97.7% (MT). LVRC may be a useful treatment for patients with advanced homogenous emphysema.
Association of FCN1 and FCN2 gene polymorphisms with earlier onset of chronic pseudomonas aeruginosa (Pa) colonisation in cystic fibrosis (CF) patients
Authors: Filomeen Haerynck, Kristel Van Steen, Tom Cattaert, Bart Loeys, Sabine Van Daele, Petra Schelstraete, Frans De Baets
Journal: European Respiratory Journal (2011)

Background: CF is a multisystem disease with high degree of phenotypic variability especially in lung disease.Modifying genes of innate immunity may be involved in early onset of Pa colonisation.

Methods: 82 Single Nucleotide Polymorphisms (SNPs) in 22 genes contributing to the innate immunity (MBL2, MASP (MBL associated serine Protease) 1/2/3, FCN (Ficolin) 1/2, LBP (Lipopolysaccharide-binding Protein), CD14,TLR (Toll-likereceptors 1→10)) were genotyped in a cohort of 116 CF patients. (age 6-44 years) Association survival analysis (Kaplan Meier and Cox regression) using additive, recessive, dominant and codominant model was performed looking for an association between SNPs and age of onset of Pa colonisation in all CF patients.

Results: CF patients being heterozygous or homozygous for the mutant allel of both linked SNPs FCN1 (promoter) (A/G) and FCN1 (Q272Q) (exon 9) (G>A) are earlier colonised with Pa (p=0,016,p=0,026 resp). Earlier onset of Pa colonisation is seen in CF patients homozygous for mutant allel of -64A>C polymorphism FCN2 (promoter) (p=0,0031) and in patients having at least one mutant allel of the linked S258A (G>T)) polymorphism FCN2 (p=0,0057).

CF patients heterozygous for mutant allel of TLR10 (rs7694115) (promoter) (T>C) (p=0,026) and linked SNP (rs11096957) (ex3) (N241H) (p=0,0113) and SNPs (rs11466645) (pro) (T>A) (p=0,0068), (rs11096956) (ex3) (P344P) (p=0,0067) are significantly later colonised with Pa .

Conclusion: Mutant allel of SNPs FCN1 (pro and Q272Q) and FCN2 (-64A>C and S258A) is significantly associated with earlier Pa colonisation. Mutant allel of polymorphism of TLR10 is associated with later onset of Pa colonisation.
Crystal structure of a T cell receptor bound to an allogeneic MHC molecule
Authors: Jean-Baptiste Reiser, Claudine Darnault, Annick Guimezanes, Claude Grégoire, Thomas Mosser, Anne-Marie Schmitt-Verhulst, Juan Carlos Fontecilla-Camps, Bernard Malissen, Dominique Housset, Gilbert Mazza
Journal: Nature Immunology (2000)
Dysphoria associated with methylphenidate infusion in borderline personality disorder
Authors: P B Lucas, D L Gardner, O M Wolkowitz, R W Cowdry
Journal: American Journal of Psychiatry (1987)

Two patients with borderline personality disorder experienced dramatic dysphoric episodes after acute administration of intravenous methylphenidate in a double-blind manner. These dysphoric episodes were similar to those which occurred spontaneously under conditions of psychological stress. Case histories and the behavioral and cardiovascular effects of the infusions are described. The pharmacology of methylphenidate is discussed in order to elucidate possible mechanisms mediating the observed responses to this drug.
Detection of the NS3 Q80K polymorphism by Sanger and deep sequencing in hepatitis C virus genotype 1a strains in the UK
Authors: A. Beloukas, S. King, K. Childs, A. Papadimitropoulos, M. Hopkins, M. Atkins, K. Agarwal, M. Nelson, A.M. Geretti
Journal: Clinical Microbiology and Infection (2015)
No evidence for involvement of the Toll-like receptor 4 (TLR4) A896G and CD14-C260T polymorphisms in susceptibility to ankylosing spondylitis
Authors: M van der Paardt
Journal: Annals of the Rheumatic Diseases (2005)

Ankylosing spondylitis (AS) is a multifactorial and polygenic disease. Apart from HLA, other genes very probably play a role in disease susceptibility. Indigenous bacteria of the gastrointestinal flora appear to play a role in the pathogenesis of the disease; therefore, genes controling the innate and acquired immune response are good candidates to study disease susceptibility. CD14 and Toll-like receptor 4 (TLR4) are key receptors for the sensing of bacteria. The CD14 C-260T and TLR4 A896G single nucleotide polymorphims are associated with aberrant signal transduction for bacterial agonists.The distribution of the CD14 C-260T and TLR4 A896G polymorphisms was studied in genomic DNA from 113 unrelated white Dutch AS patients and 170 ethnically matched healthy controls. The diagnosis of AS was made according to the modified New York criteria. The CD14 C-260T and TLR4 A896G polymorphisms were genotyped by PCR-RFLP methods.No significant differences were found between patients and controls in the frequencies of the carriership of the less frequent CD14-260T allele (odds ratio 0.65; 95% confidence interval 0.37 to 1.15) or the TLR4 896G allele (1.68; 0.67 to 4.19).There is no evidence for involvement of the CD14 C-260T or TLR4 A896G polymorphisms in susceptibility to AS. An important role of bacteria and genetic predisposition of the innate immune system in cases of AS cannot be excluded by these findings. Therefore, studies of the surprisingly highly polymorphic candidate genes in this field should be continued.
Tumor-extracellular matrix interactions: Identification of tools associated with breast cancer progression
Authors: Marta Giussani, Giuseppe Merlino, Vera Cappelletti, Elda Tagliabue, Maria Grazia Daidone
Journal: Seminars in Cancer Biology (2015)

Several evidences support the concept that cancer development and progression are not entirely cancer cell-autonomous processes, but may be influenced, and possibly driven, by cross-talk between cancer cells and the surrounding microenvironment in which, besides immune cells, stromal cells and extracellular matrix (ECM) play a major role in regulating distinct biologic processes. Stroma and ECM-related signatures proved to influence breast cancer progression, and to contribute to the identification of tumor phenotypes resistant to cytotoxic and hormonal treatments. The possible clinical implications of the interplay between tumor cells and the microenvironment, with special reference to ECM remodelling, will be discussed in this review.
Ethical Issues in Embryonic Stem Cell Research—Reply
Authors: Cynthia B. Cohen
Journal: JAMA (2001)

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Rational clinical examination: The clinical epidemiology of physical signs taught in respiratory medicine
Authors: Rahil Kassamali, Shiva Bikmalla, Vikas Punamiya, Tandra Ghosh, Rahul Mukherjee
Journal: European Respiratory Journal (2012)

Background: Current clinical epidemiology research defines precision and accuracy of items of clinical examination [Stone H, Mukherjee R. Evidence based clinical teaching in respiratory medicine. Proceedings of the Association for Medical Education in Europe 2007; 2 : 5. (AMEE 2007: Trondheim, Norway)]. We set out to examine if doctors naturally carry out the more precise items of respiratory clinical examination from the repertory they learn as part of routine education.

Methods: An online questionnaire was emailed to doctors in the Heart of England NHS Foundation trust to all grades of doctors.

Results: Responses were received from 105 participants from a range of specialties and grades. The majority frequently carried out the respiratory examination as a routine with some items of high precision, although the kappa values of individual items (signifying precision) tend to correlate with items of routine respiratory examination which doctors naturally think are more useful.

![Figure][1] 



Conclusion: Practising doctors tend to develop their own rational examination routine which can be improved by adding items of high precision (e.g. crico-sternal distance), which are not routinely taught. Explicit teaching of the rationale for clinical examination and the quantitative aspect of clinical reasoning based on evidence can be included in the clinical teaching of undergraduate medical students to make it relevant and useful.

 [1]: pending:yes
Central nervous system toxicity following the treatment of pediatric patients with ifosfamide/mesna.
Authors: C B Pratt, A A Green, M E Horowitz, W H Meyer, E Etcubanas, E Douglass, F A Hayes, E Thompson, J Wilimas, M Igarashi
Journal: Journal of Clinical Oncology (1986)

Ifosfamide/mesna treatment of 50 patients with pediatric malignant solid tumors was associated with the development of neurotoxic signs and symptoms in 11 of these individuals who received 29 courses of treatment. Neurologic toxicity included changes in mental status, cerebellar function, cranial nerve, and cerebellar and motor system function, including seizures. All symptoms, signs, and EEG abnormalities were transient. Some of the affected individuals failed to develop acute neurotoxic signs of symptoms when retreated with ifosfamide. A grading system for scoring these neurologic abnormalities is presented for comparison of acute neurotoxic effects of other agents. Recommendations are made regarding early termination or delay of ifosfamide/mesna treatments in the presence of significant neurotoxicity.
Cancer Detection: Microneedle Biosensor for Real-Time Electrical Detection of Nitric Oxide for In Situ Cancer Diagnosis During Endomicroscopy (Adv. Healthcare Mater. 8/2015)
Authors: Do Hee Keum, Ho Sang Jung, Taejun Wang, Myeong Hwan Shin, Young‐Eun Kim, Ki Hean Kim, G‐One Ahn, Sei Kwang Hahn
Journal: Advanced Healthcare Materials (2015)

A novel microneedle biosensor is developed on page 1153 for real-time electrical detection of nitric oxide (NO) for in situ cancer diagnosis during endomicroscopy. S. K. Hahn and co-workers show that the dual diagnostic system of endomicroscope and microneedle biosensor demonstrates high resolution imaging combined with electrical detection of NO released from cancer tissues as a new platform for facile, rapid, and accurate diagnosis of cancers.
Complete removal of the tumor-bearing portal territory decreases local tumor recurrence and improves disease-specific survival of patients with hepatocellular carcinoma
Authors: Junichi Shindoh, Masatoshi Makuuchi, Yutaka Matsuyama, Yoshihiro Mise, Junichi Arita, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Norihiro Kokudo
Journal: Journal of Hepatology (2015)
Advances in managing chronic disease
Authors: R. M Davis
Journal: BMJ (2000)

Chronic diseases have been around as long as humans. But now, in most industrialised nations and in many developing countries, they predominate among the leading causes of death.1 For many years public health practitioners have recognised the increasing burden of chronic illness.2

Just as chronic disease control has developed into a distinct discipline in public health, so chronic disease management is beginning to develop its own identity as an important component of health care. No longer is each chronic illness—asthma, diabetes, arthritis, etc—being considered in isolation. Awareness is increasing that similar strategies can be equally effective in treating many different conditions. In recognition of the maturing field, this issue of the BMJ— and the February issue of its sister journal, the Western Journal of Medicine —is devoted to chronic disease management.

Three essential ingredients are required for continued progress in chronic disease management: research, performance measurement, and quality improvement. Research on innovative methods to treat people with chronic illness should be high on the agenda of organisations that fund health research. The Robert Wood Johnson Foundation, a leading American philanthropic institution, has already designated chronic disease care as one of its major priorities (www.rwjf.org), and its programme emphasises the commonalities of effective …
Use of a high-density DNA probe array for detecting mutations involved in rifampicin resistance in Mycobacterium tuberculosis
Authors: W. Sougakoff, M. Rodrigue, C. Truffot-Pernot, M. Renard, N. Durin, M. Szpytma, R. Vachon, A. Troesch, V. Jarlier
Journal: Clinical Microbiology and Infection (2004)
Human Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes home preferentially to and induce selective regressions of autologous EBV-induced B cell lymphoproliferations in xenografted C.B-17 scid/scid mice.
Authors: J F Lacerda, M Ladanyi, D C Louie, J M Fernandez, E B Papadopoulos, R J O'Reilly
Journal: The Journal of Experimental Medicine (1996)

C.B-17 scid/scid (severe combined immunodeficiency [SCID]) mice inoculated with peripheral blood lymphocytes from Epstein-Barr virus (EBV)-seropositive donors, or with EBV-transformed lymphoblastoid B cell lines (EBV-LCL), develop lethal human EBV+ B cell lymphoproliferative disorders (EBV-LPD) with characteristics similar to those arising in immunodeficient patients. Using this model, we examined the capacity of human effector cells to control human EBV-LPD. SCID mice received rabbit anti-asialo GM1 antiserum to abrogate endogenous natural killer-cell function. Preliminary experiments showed that adoptive transfer of peripheral blood mononuclear cells (PBMC), purified T cells, interleukin (IL) 2-activated PBMC or anti-CD3-activated T cells derived from EBV-seropositive donors did not result in improved survival of treated mice (in vivo effector/target ratio 2:1 to 1:1). In contrast, EBV-specific cytotoxic T lymphocytes (CTL), derived from EBV-seropositive donors and expanded in vitro, exhibited strong EBV-specific and HLA-restricted activity both in vitro and in vivo. SCID mice inoculated intraperitoneally with autologous but not with HLA-mismatched EBV-LCL had significantly improved survival relative to untreated mice after inoculation of EBV-specific CTL either intraperitoneally (P&amp;lt;0.001) or intravenously (P&amp;lt;0.001) (in vivo effector/target ratio 1:1). SCID mice bearing large subcutaneous EBV+ tumors and treated intravenously with 10(7) EBV-specific CTL achieved complete tumor regression. Both CTL- and CTL-plus-IL-2-treated mice survived significantly longer than untreated animals or animals treated with IL-2 alone (P = 0.0004 and P&amp;lt;0.02, respectively). SCID mice bearing two subcutaneous EBV+ tumors, one autologous and the other HLA mismatched to the EBV-specific CTL donor, had regression of only the autologous tumor after intravenous infusion of 10(7) EBV-specific CTL. Moreover, we could demonstrate preferential homing of PKH26-labeled EBV-specific CTL to autologous but not to HLA-mismatched EBV+ tumors as early as 24 h after intravenous adoptive transfer. Immunophenotypic analyses also demonstrated preferential infiltration of T cells into the autologous EBV+ tumor in SCID mice bearing both the autologous and either fully HLA-mismatched or genotypically related haplotype-sharing EBV+ tumors. The human T cells infiltrating EBV+ tumors were CD3+ and, predominantly, CD8+CD4-. Our results indicate that EBV-specific CTL preferentially localize to and infiltrate EBV+ tumors bearing the appropriate HLA antigens and thereafter induce targeted regressions of disease.