tbuckley/cabot-search huggingface dataset:
Vascular targeting of nanoshells for photothermal cancer therapy.
Authors: Amanda R. Lowery, Andre M. Gobin, Naomi J. Halas, Jennifer L. West
Journal: Clinical Cancer Research (2006)

B83   Photothermal cancer therapy using targeted nanoshells may enable the preferential destruction of cancer cells while minimizing damage to healthy tissue. Nanoshells possess an optical tunability that spans the near infrared (NIR) - a region where light penetrates tissues deeply. Conjugated with tumor-targeting molecules, NIR absorbing nanoshells could be systemically injected and preferentially bound to tumor sites. NIR light heats the tumor-bound nanoshells, thus destroying the tumor.  In vitro  and  in vivo  studies confirmed the ability to selectively induce cell death with the photothermal interaction of nanoshells and NIR light. Previous studies demonstrated the ability of PEG-coated nanoshells to passively accumulate at a tumor site. Complete regression of tumors was observed in animals receiving systemic injections of nanoshells prior to NIR laser treatment. Furthermore, the tissue damage from the NIR laser therapy was confined to the tissue region receiving both nanoshells and laser irradiation. Nanoshells can be targeted to cancer cells or tumor vasculature by the conjugation of tumor specific antibodies to the gold surface. These targeted nanoshells may increase the cellular specificity of nanoshell binding and improve the therapeutic results.Gold nanoshells were manufactured as previously described. Briefly, silica cores were fabricated by the reduction of tetraethoxysilane in ethanol. Following amine functionalization, gold colloid was adsorbed to silica surface. Reduction of additional gold completes the shell. The nanoshells used in the following study had a 110 nm core diameter with a 10 nm thick gold shell and a peak extinction at ~820 nm. Soluble vascular endothelial growth factor (VEGF) was conjugated to the gold nanoshells through a bifunctional PEG linker, containing N-hydroxy succihimide for coupling and an orthopyridyl-disulfide for attachment to the gold surface. In vitro , targeted nanoshells were incubated with murine endothelial cells at 2.9x10 9  particles/mL. Unbound nanoshells were rinsed from the surface with PBS and replaced with fresh medium. Control cells were incubated with PEG-coated nanoshells without targeting molecules. After exposure to NIR light (820 nm, 1.55 W, 1.5 mm diameter spot, for 7 min), the cells were incubated overnight at 37 o C. Cell viability was assessed by staining with calcein AM. Nanoshells were visualized by silver staining.Cell death was confined within the laser spot for cells incubated with properly targeted nanoshells. Silver staining verified the presences of nanoshells. Control nanoshells did not bind to the cells, as indicated by silver staining, and control cells continued to be viable after irradiation. Nanoshells show promise as a minimally invasive cancer therapy. The nanoshells are biocompatible and display selective photothermal destruction of tissue by absorption of NIR light. Targeting may improve the cellular specificity of the nanoshell therapy.
Determining the site of pharyngeal collapse in sleep apnea patients from the inspiratory flow pattern
Authors: Andrew Wellman, Pedro Genta, Owens Robert, White David, Kezirian Eric
Journal: European Respiratory Journal (2014)

Rationale: The upper airway can collapse at a variety of sites in patients with OSA. However, site-specific surgery is currently not an option for many patients due to the difficulty in determining the site of collapse. Furthermore, recent evidence shows that different OSA patients exhibit distinct and characteristic inspiratory flow shapes during sleep. We hypothesized that the site of pharyngeal collapse in an individual could be determined from the shape of their inspiratory flow signal.  Method: To answer this hypothesis, 40 individuals with sleep apnea were studied during natural sleep endoscopy with simultaneously measured airflow. Flow was measured with a pneumotach and the site of airway collapse was visualized with a pediatric bronchoscope. Collapse was produced by slowly lowering CPAP to several cmH2O below the therapeutic level. The site if airway collapse was categorized using the VOTE classification (velum, oropharyngeal lateral walls, tongue base, and epiglottis). The configuration of airway collapse (AP, lateral, concentric) was also classified. The inspiratory flow shape was quantified as the percent reduction in airflow between the peak flow (early in inspiration) and the flow at peak negative epiglottic pressure (during mid/late inspiration).  Results: Patients with collapse primarily at the palate exhibited a small reduction in flow from early to late inspiration. On the other hand, collapse at any of the other sites exhibited a more scooped-out inspiratory flow shape (large reduction peak flow from early to late inspiration).  Conclusion: Analysis of the inspiratory flow shape could yield important structural information for guiding pharyngeal surgery.
Clinical study of mycobacterium avium complex pulmonary disease complicated by interstitial pneumonia
Authors: Hisako Tabata, Yoshiro Mochizuki, Yasuharu Nakahara, Tetsuji Kawamura, Shin Sasaki, Hiroko Okamoto, Akie Morimoto, Tetsuichiro Mayumi, Hiroaki Tukamoto, Yasuyuki Mizumori, Tomoko Miyagawa, Toshihide Yokoyama, Etsuko Watanabe, Rinko Katsuda, Kazuyuki Mimura, Ryogo Kagami, Yasutaka Onishi
Journal: European Respiratory Journal (2011)

Background/Aims:  We have encountered patients with mycobacterium avium complex (MAC) complicated by interstitial pneumonia (IP) and have had the following questions: 1) Does IP induce MAC as a baseline disease? and, 2) Does steroid therapy for IP cause deterioration of MAC?   Methods:  We retrospectively examined the medical records of patients with MAC and/or with IP who consulted at the department of respiratory medicine, Himeji Medical Center, Japan between January 2000 and December 2008, and investigated their clinical course based on chest radiography and CT images.   Results:  Of 29,799 patients who consulted at our department in this period, 346 cases were patients with MAC, 1544 cases had IP, and 18 patients had both MAC and IP. There was no significant difference in the prevalence of MAC between IP patients and IP-free patients (0.0115 vs. 0.0116, p=0.797, chi 2 test).  Among 18 patients with both MAC and IP, no difference was seen in the response rate to anti-MAC medication between the steroid-treated group (4/4 cases) and the non-treated group (3/3 cases). Among the patients not receiving anti-MAC medications, little difference was seen in the clinical course of MAC between the steroid-treated group (n=7) and non-treated group (n=4).   Conclusions:  IP did not significantly increase the prevalence of MAC. No apparent difference was seen in the clinical course of MAC whether or not steroid was administered for IP.
Efficacy of targeted lung denervation in patients with moderate to severe COPD
Authors: Dirk-Jan Slebos, Karin Klooster, Coenraad Koegelenberg, Johan Theron, Dorothy Steyn, Martin Mayse, Chris Bolliger
Journal: European Respiratory Journal (2014)

Background: Acetylcholine derived from parasympathetic nerves is a well-validated target for treatment of patients with COPD. Targeted lung denervation (TLD) is a novel bronchoscopic therapy that ablates parasympathetic pulmonary nerves along the main bronchi.  Aim: Evaluate impact of TLD on COPD patients.  Methods: A first-in-human, prospective, multicenter, study in COPD patients (FEV 1 /FVC 1  30-60% predicted; >15% reversible to ipratropium) was performed (NCT01483534). TLD was performed using a lung denervation system (Holaira, Inc., USA) at either 15W or 20W energy doses following baseline assessment of pulmonary function, exercise testing and quality of life off bronchodilators. This assessment was repeated up to 365 days after TLD.  Results: Twenty-two patients were treated in a staged fashion, 12 (FEV 1  33.8±9.4 % predicted, 58.3% male, age 62.9±11.4 yrs) at a 20W energy dose and 10 (FEV 1  34.5±6.3 % predicted, 40% male, age 64.4±8.9 yrs) at 15W. Change from baseline in FEV 1 , submaximal exercise endurance, and SGRQ for the 20W group are shown as mean±SEM in the Figure. When compared, the 20W group has a larger improvement on these parameters than the 15W group.  Conclusion: TLD provides durable bronchodilation, improvements in exercise endurance and quality of life out to 1 year. This is the first study reporting bronchoscopic nerve ablation for the treatment of COPD. A large-scale randomized study is planned.
Abstract 310: Production of Basal Lamina Collagen IV by Cardiac Fibroblasts in 3-Dimensional Cultures
Authors: Amy Bradshaw, Jessica Trombetta eSilva, Erik Eadie, Thomas K Borg
Journal: Circulation Research (2014)

Cardiac fibroblasts are generally considered the primary cell type that controls extracellular matrix homeostasis in the heart. Distinct changes in amounts and composition of extracellular matrix occur from birth to old age. Accordingly, age-dependent alterations in cardiac extracellular matrix are an important factor governing response to injury and pathological remodeling. Whereas cardiac myocytes are surrounded by a basal lamina, cardiac fibroblasts do not assemble a cell-adjacent basal lamina. Evidence is presented that in addition to fibrillar collagen production, cardiac fibroblasts are also the primary cell type responsible for the production of collagen IV. First, patterns and abundance of collagen IV in murine heart was established in sections from neonate, adult, and aged mice. Second, production of collagen IV by fibroblasts grown in 3-D fibrin gels was assessed by confocal microscopy and quantification by immmunoblot analysis. Finally, co-cultures of cardiac fibroblasts with myocytes were performed to show that fibroblasts are the primary cell type producing collagen IV under these conditions. The basal lamina of the myocytes plays a critical role in aligning and tethering myocytes together as well as making connections to the interstitial collagen fibers of the heart. Hence, production of collagen IV by cardiac fibroblasts would provide a mechanism by which cardiac fibroblasts assist in aligning and securing cardiac myocyte alignment and structural integrity via basal lamina production.
Comparative in vitro performance of a new re-usable breath-actuated nebulizer (BAN) with other high performance systems intended for domiciliary use - 2: Portable battery-compressor
Authors: Jamie Malpass, Mark Nagel, Valentina Avvakoumova, Rubina Ali, Heather Schneider, Jolyon Mitchell
Journal: European Respiratory Journal (2012)

RATIONALE:  Treatments with home based compressor/nebulizer systems can offer very different delivery characteristics. We evaluated a new, reusable BAN (AeroEclipse-XL®, Trudell Medical International) in breath-actuated mode with its portable (Ombra®) battery-compressor.  METHODS:  The nebulizer-on-test (n=5/group) was filled with 2.5-mL, 1.0 mg/mL albuterol (Ventolin®, GSK Canada Inc.), and connected to a breathing simulator (ASL5000, IngMar Medical, Pittsburgh, PA) mimicking adult tidal breathing (V t = 600-mL; duty cycle = 33%; rate = 10 cycles/min). Emitted aerosol was captured on a filter at the mouthpiece, replaced at minute intervals until onset of sputtering, defining run time. Recovery/assay of salbutamol was undertaken by HPLC-UV spectrophotometry. Fine droplet fraction (FDF  ) was the product of total mass and FDF  . Comparative measurements were made with the Sprint® (PARI, Germany) and MicroPlus® (Philips-Respironics, Germany) nebulizers using PARI BOY® Mobile S® and Inspiration Micro Elite® portable compressors respectively.   RESULTS:  See Table   CONCLUSIONS:  The BAN/Ombra® system provided highly respirable aerosol with FDM   substantially greater than the benchmark systems. Its run time reflects the fact that aerosol is only delivered during inhalation and not wasted to the environment.
Medulloblastoma in very young children: outcome of definitive craniospinal irradiation following incomplete response to chemotherapy.
Authors: A Gajjar, R K Mulhern, R L Heideman, R A Sanford, E C Douglass, E H Kovnar, J A Langston, J J Jenkins, L E Kun
Journal: Journal of Clinical Oncology (1994)

PURPOSE To evaluate survival and neurodevelopmental outcomes following radiation therapy in infants and young children with residual or progressive medulloblastoma after primary chemotherapy. PATIENTS AND METHODS Thirteen young patients (&lt; or = 36 months old) with medulloblastoma were treated with preirradiation multiagent chemotherapy and maximal surgical resection. Patients were scheduled to receive radiation therapy at the time of documented disease progression or upon completion of chemotherapy with residual disease. All patients underwent neurodevelopmental evaluation at the time of diagnosis, before receiving radiation therapy, and at yearly intervals posttreatment. RESULTS Two patients completed the scheduled chemotherapy with residual disease and received delayed radiation therapy. The remaining 11 patients had either local or leptomeningeal progression during chemotherapy (median time to progression, 5 months). Six patients had a complete response (CR) to radiation therapy, and three of these children are alive 48 to 104 months postdiagnosis. Of the five patients who had progressive disease (PD) during radiation therapy or residual imaging abnormalities after treatment, only one is alive (with stable enhancing leptomeningeal abnormalities) 48 months postirradiation. Two additional survivors were rendered disease-free by surgical resection before radiation therapy and are without evidence of disease at 91 and 107 months after diagnosis. Thus, six of 13 patients are alive at 48 to 107 months postdiagnosis. Neurodevelopmental scores tended to be below age norms at diagnosis; scores improved during chemotherapy, but then decreased during posttreatment follow-up evaluation. CONCLUSION Radiation therapy appears to produce long-term disease-free survival in a proportion of very young patients who have progressive or residual medulloblastoma during or after primary chemotherapy. However, neurodevelopmental deficits are frequent among long-term survivors.
The Texas Advanced Directive Law: Unfinished Business
Authors: Michael Kapottos, Stuart Youngner
Journal: The American Journal of Bioethics (2015)

The Texas Advance Directive Act allows physicians and hospitals to overrule patient or family requests for futile care. Purposefully not defining futility, the law leaves its determination in specific cases to an institutional process. While the law has received several criticisms, it does seem to work constructively in the cases that come to the review process. We introduce a new criticism: While the law has been justified by an appeal to professional values such as avoiding harm to patients, avoiding the provision of unseemly care, and good stewardship of medical resources, it is applied incompletely. It allows physicians and institutional committees to refuse "futile" treatments desired by patients and families while at the same time providing no way of regulating physicians who recommend or even push "futile" treatments in similar cases. In this sense, the TADA is incomplete on its own terms.
Distinctive intrahepatic characteristics of paediatric and adult pathogenesis of chronic hepatitis C infection
Authors: P. Valva, M.I. Gismondi, P.C. Casciato, M. Galoppo, C. Lezama, O. Galdame, A. Gadano, M.C. Galoppo, E. Mullen, E.N. De Matteo, M.V. Preciado
Journal: Clinical Microbiology and Infection (2014)
Diagnostic value of Von Willebrand factor (VWF) in patients suffering from respiratory distress
Authors: Rabab El Wahsh, Safaa Amin, Enas Essa
Journal: European Respiratory Journal (2011)

Introduction:  Acute respiratory distress syndrome (ARDS) is characterized by an extensive alveolar capillary leak. Von Willebrand Factor antigen (VWF) is a macromolecular antigen that is considered as a marker of endothelial activation.   Aim:  To investigate the diagnostic value of VWF antigen in patients with ALI/ARDS caused by poisoning or non-poisoning etiology.   Patients and methods:  VWF antigen was measured in 52 patients with ALI/ARDS, 13 poisoned patients without ALI/ARDS and 20 control subjects.   Results:  There was a highly significant difference between VWF level in patients and control groups (P≤ 0.001). VWF level had a significant negative correlation with the ratio between PaO 2  and FIO 2  in patients with respiratory distress. There was a non significant difference in VWF level between poisoned and non- poisoned cases. There was a significant relationship between the level of VWF and the severity of poisoning in patients with respiratory distress. Among the poisoned patients, the highest level of VWF was in patients with anticholinesterase poisoning. The difference between VWF level in poisoned patients with ALI/ARDS and those without was highly significant. The level of VWF didn9t affect patients9 need for mechanical ventilation or their mortality. The cut –off value of VWF at 100% sensitivity and 20% specificity was 0.99 units, while the cut –off value of VWF at 100% specificity and 60% sensitivity was 1.87 units.   Conclusion:  VWF has a diagnostic value for ALI/ARDS but it does not differentiate between poisoning or non-poisoning etiology, nor does it predict outcome of the illness. VWF is significantly increased in patients with anticholinesterase poisoning.
RandomizEd phase II trial of Sunitinib four weeks on and two weeks off versus Two weeks on and One week off in metastatic clear-cell type REnal cell carcinoma: RESTORE trial
Authors: J.L. Lee, M.K. Kim, I. Park, J.-H. Ahn, D.H. Lee, H.M. Ryoo, C. Song, B. Hong, J.H. Hong, H. Ahn
Journal: Annals of Oncology (2015)
Effects of abdominal binding on chest wall kinematics in tetraplegic individuals
Authors: Sabine K. Illi, Stefanie Hostettler, Andrea Aliverti, Robert Brown, Gabi Mueller, Christina M. Spengler
Journal: European Respiratory Journal (2012)

Introduction:  Tetraplegic individuals show a paradoxical inward motion of the ribcage during inspiration. Abdominal binding is supposed to decrease paradoxical breathing by decreasing abdominal compliance and increasing the zone of apposition of the diaphragm. We hypothesized that abdominal binding would reduce the paradox during quiet breathing (QB) as well as during different levels of hyperpnoea (HYP) and increase maximal voluntary ventilation (MVV).   Methods:  Chest wall kinematics were assessed by optoelectronic plethysmography in three male complete tetraplegics (C4-C7) during QB and during HYP at 40 and 100% MVV with and without abdominal binding. Tidal volume (V T ) was partitioned into the relative contribution of the pulmonary rib cage (ΔV RCP ), abdominal rib cage (ΔV RCA ), and abdomen (ΔV AB ). Inspiratory paradox time (IPT) was calculated as the percentage of inspiratory time (T I ) with a decrease in V RCP  and/or V RCA .   Results:  Abdominal binding reduced IPT at all ventilatory levels. The reduction was higher in RCA than in RCP. At rest, abdominal binding increased ΔV RCA  more effectively than ΔV RCP . MVV was larger with abdominal binding in all subjects (105.1±49.0 vs. 92.0±53.9 l•min -1  without abdominal binding).   Conclusion:  The reduction in IPT and the increase in MVV in tetraplegic individuals suggest a functional benefit of abdominal binding which is mainly seen in the lower rib cage (RCA).   Support:  SNF grant no. 32-116777.
Phase II trial of the Hsp90 inhibitor tanespimycin (Tan) + trastuzumab (T) in patients (pts) with HER2-positive metastatic breast cancer (MBC)
Authors: S. Modi, S. Sugarman, A. Stopeck, H. Linden, W. Ma, K. Kersey, R. G. Johnson, N. Rosen, A. L. Hannah, C. A. Hudis
Journal: Journal of Clinical Oncology (2008)

1027 Background: Tan (17-AAG) inhibits Hsp90 activity, resulting in degradation of client proteins including the HER2 receptor. A phase 1 trial demonstrated clinical activity of T + Tan in pts with HER2+ MBC (1 PR + 4 MRs in 15 pts with median of 2 prior T-based regimens; Modi et al, JCO 2007). Tan was initially a Cremophor-based product; a suspension became available and was substituted in this phase 2 trial. Methods: Eligible pts have HER2+ MBC and either PD within 3m following adjuvant T or PD following 1-line of T-based therapy for MBC. Pts receive standard weekly doses of T followed by Tan (450 mg/m2). Early pts received a Cremophor-based Tan product with antihistamine/steroid premeds. Later pts received the suspension Tan product without premeds. Primary endpoint: ORR by RECIST, disease status assessed every 8w. Results: As of 19Dec07, 29 pts enrolled (mean age 54 yrs, range 31–71; median KPS 90). 21 pts received Cremophor product; 8 pts received suspension product (4 pts crossed-over to the suspension product). 21 pts are evaluable for efficacy. Drug-related toxicity: fatigue (39%), diarrhea (33%), dizziness (24%) and headache (19%). Grade 3 drug-related toxicity in 3 pts (headache/fatigue; ↑ LFTs; and unsteady gait/euphoria, diarrhea), all reversible; 1 pt withdrawn for toxicity. Toxicities common to cytotoxic chemotherapy noticeably absent (alopecia, myelosuppression, peripheral neuropathy). Activity: 5 pts have a confirmed PR (1) 75% decrease in liver metastases, 8 months (m) on study; (2) 45% decrease in hilar node, 15+m/active; (3) 33% decrease in right breast lesion, 7+m /active; (4) 57% decrease in lymph nodes, liver, and left breast lesions, on study 7m; (5) 37% decrease in lymph nodes, 5+m/active. All 4 active pts maintained PR when cross-over to the new formulation. Two additional pts had MR with ↓ tumor markers (6 and 5 m); 5 pts had SD for 4, 4, 4+, 7 and 8 m. Conclusions: The combination of T + Tan is active in pts with HER2+ MBC with progression on T-based therapy (response rate of 24% and clinical benefit rate of 57%). Toxicity is very manageable. The newer suspension product produces a similar safety profile with responses maintained upon cross-over. Accrual continues on the suspension product. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Kosan Biosciences Kosan Biosciences Kosan Biosciences Kosan Biosciences
Leukocyte Migration Inhibition in Human Pulmonary Neoplasia 2
Authors: B. M. Vose, I. Kimber, M. Moore
Journal: JNCI Journal of the National Cancer Institute (1977)

Peripheral blood leukocytes from 65 lung cancer patients, 69 healthy donors, 33 patients with malignant disease outside the lung, and 24 patients with nonmalignant pulmonary conditions were examined for immune reactivity, as measured by the leukocyte migration inhibition assay, to antigens in homogenates of lung tumor tissue and material derived from tumor-free lung areas and a nonmalignant lung lesion. A low level of reactivity with apparent specificity was detected in the lung cancer patient group, with 17/52 showing migration inhibition with extracts of lung tumor tissue. Reactivity was also detectable in this group against homogenates of tumor-free lung and nonmalignant lung lesion. The data supported the conclusion that sensitization at least in some patients with lung cancer might be directed not only against tumor-specific antigens but also against antigens of less confined disease association.