tbuckley/cabot-search huggingface dataset:
CICATRIZATION OF WOUNDS
Authors: P. Lecomte Du Noüy
Journal: The Journal of Experimental Medicine (1916)

The first article of this series showed that it was possible to express mathematically the phenomenon of cicatrization. The principal point consisted in determining by means of an equation, a constant, or index, characterizing each wound. The calculation had to be made for each patient for each wound, and required two observations, 4 days apart. The index having proved to be a continuous function of the size of the wound and of the age of the patient, of the form See PDF for Equation where S is the area, i the index, a a decimal exponent, and K a constant, it was then possible to draw a chart by means of which this index i could be obtained without calculation. The advantage of the new way of determining the index is, above all, that this index is a general, average, normal index, and no longer an individual index. Hence, the differences between the observed rate of cicatrization of man and the normal rate may give some indication of the general state of the patient. Another advantage is that the determination of the index is no longer controlled by the temporary accidents which may happen between the two observations of S and S'.
The Prognostic Impact of Septal Myectomy in Obstructive Hypertrophic Cardiomyopathy**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Hugh Watkins, William J. McKenna
Journal: Journal of the American College of Cardiology (2005)
Phase II study of RAD001 (everolimus) and depot octreotide (Sandostatin LAR) in patients with advanced low grade neuroendocrine carcinoma (LGNET)
Authors: J. C. Yao, A. T. Phan, D. Z. Chang, C. Jacobs, J. E. Mares, A. Rashid, F. Meric-Bernstam
Journal: Journal of Clinical Oncology (2006)

4042 Background: Effective systemic therapy for advanced LGNET is lacking. Patients with mutation in TSC2, an endogenous inhibitor of mTOR develop LGNET. mTOR also mediate signaling downstream of IGF1 and VEGF, pathways important in LGNET. RAD001 inhibits the serine-threonine kinase activity of mTOR. Octreotide may have cytostatic activity and has been described to inhibit VEGF and IGF1 production in solid tumors. Methods: Treatment consisted of depot octreotide 30 mg IM q28 days, and RAD001 5 or 10 mg po daily. Response evaluation is performed every 12 weeks. Results: 32 patients (18 carcinoids, 13 islet cell) were enrolled between 2/05 - 1/06. 20 had prior octreotide. 27 patients have completed 12 weeks of therapy at the 5 mg dose level and undergone response evaluation. By RECIST criteria, response rate was 15%. There were 4 PR, 19 SD (including 4 patients having 18–28% reduction), 4 PD. PR occurred in 2 carcinoids, and 2 islet cell. PFS rate at week 24 was 71%. Of 21 patients with radiological progression prior to study entry, 17 have completed 12 weeks of therapy. Among these, there were 3 PR, 10 SD, 4 PD. Of 18 patients with elevated chromogranin A at baseline, 9 (50%) patients had &gt; 50% reduction. Treatment is generally well tolerated. The most common toxicity is mild aphthous ulceration. CTC G3/4 toxicity include: anemia (1), thrombocytopenia (1), leukopenia (1), fatigue (3), aphthous ulcer (2), diarrhea (2), hypoglycemia (2), pain (2), rash (2), hyperglycemia (1), edema (1), nausea (1). Conclusions: RAD001 5 mg po daily is well tolerated in combination with Depot Octreotide. Anti-tumor activity has been observed. An additional cohort will be treated at RAD001 10 mg daily dose. Optional blood draws and tumor biopsies will be performed to help assess biomarkers that may predict benefit. No significant financial relationships to disclose.
A nanoparticle therapeutic vaccine targeting HAAH stimulates cellular immunity
Authors: Michael Lebowitz, Solomon Stewart, Susan Walker, Samindhi Wu, Steven Fuller, Hossein Ghanbari
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts We are evaluating the immunogenicity and efficacy of a nanoparticle vaccine (NPV) targeting the tumor marker human aspartyl (asparaginyl) β-hydroxylase (HAAH). HAAH is an embryonic protein that is over-expressed on the surface of cancer cells, is demonstrated to be responsible
Novel human hepatic organoid model enables testing of drug-induced liver fibrosis in vitro
Authors: Sofia B. Leite, Tiffany Roosens, Adil El Taghdouini, Inge Mannaerts, Ayla J. Smout, Mustapha Najimi, Etienne Sokal, Fozia Noor, Christophe Chesne, Leo A. van Grunsven
Journal: Biomaterials (2015)
Burden of disease scoring in epidermolysis bullosa
Authors: D.F. Murrell
Journal: British Journal of Dermatology (2015)

Journal Article Burden of disease scoring in epidermolysis bullosa Get access D.F. Murrell D.F. Murrell Department of Dermatology St George Hospital Gray St, Kogarah Sydney NSW AustraliaFaculty of Medicine University of New South Wales Sydney NSW Australia https://orcid.org/0000-0003-2971-0199 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 6, 1 December 2015, Pages 1357–1358, https://doi.org/10.1111/bjd.14246 Published: 01 December 2015
Abstract #LB-211: CYT997: Preclinical studies on the antivascular effects and mode of action of a phase II vascular disrupting agent.
Authors: David Segal, Pradnya Gangatirkar, Max Joffe, Steven Shnyder, Cathy Malcontenti-Wilson, Chris Christophi, Andrew Powell, Gregg Smith, Christopher Burns, Emmanuelle Fantino
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

CYT997 is an orally available synthetic small molecule that is currently in phase II clinical studies within different oncology settings. CYT997 has been shown to exhibit potent vascular disrupting activity in vivo at doses well below its maximum tolerated dose. We have modeled this activity in vitro and found that CYT997 potently inhibited the proliferation of HUVEC primary endothelial cells at low nM concentrations. In order to evaluate the acute vascular effect of CYT997 on blood flow through tumour tissue in vivo , we have used Laser Doppler Flowmetry to measure blood flow in a mouse model of metastatic colorectal cancer. Oral administration of CYT997 led to a significant reduction in tumour blood flow 15 minutes post administration and this effect persisted for up to 96hrs post administration. Similarly, in athymic nude mice bearing subcutaneous DLD-1 human colon adenocarcinoma xenografts a single oral dose of CYT997 led to a time and concentration dependent shutdown of tumour vasculature. The observed vascular shutdown was rapid and was detected at 1-hour post administration of CYT997. Significant vascular shutdown was maintained in tumours at 24-hours post administration of CYT997 and subsequent histology demonstrated greater necrosis of the tumour core in mice treated with CYT997. In addition to vascular disrupting activity, CYT997 also causes G2/M cell cycle arrest and apoptosis of tumor cell lines. Time course analysis of the cell cycle in HCT-15 cells was performed and showed that CYT997 (250 nM) markedly and rapidly increased the fraction of cells in G2/M. As CYT997 is under clinical development as a therapy to be used in conjunction with current antitumor therapies we have assessed the combination of CYT997 and a number of clinically used anti-cancer agents with a range of different modes of action, on the proliferation of HCT-15 liver adenocarcinoma cells. CYT997 demonstrated marked synergy with 5FU (CI=0.55 at IC50), paclitaxel (CI=0.60 at IC50), and vincristine (CI=0.35 at IC50). In contrast, the kinase inhibitor sorafenib did not affect CYT997 activity on HCT-15 cell viability. Together, these findings clearly demonstrate that CYT997 is an orally available vascular disrupting agent that reduces tumour blood flow in a dose dependent manner in a two murine cancer models and raises the possibility that CYT997 may exhibit increased efficacy in combination with other common anticancer therapies.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-211.
Anticancer Effects of Mesothelin-Targeted Immunotoxin Therapy Are Regulated by Tyrosine Kinase DDR1
Authors: Fatima Ali-Rahmani, David J. FitzGerald, Scott Martin, Paresma Patel, Marco Prunotto, Pinar Ormanoglu, Craig Thomas, Ira Pastan
Journal: Cancer Research (2016)

Recombinant immunotoxins (RIT) have been highly successful in cancer therapy due, in part, to the high cancer-specific expression of cell surface antigens such as mesothelin, which is overexpressed in mesothelioma, ovarian, lung, breast, and pancreatic cancers, but is limited in normal cells. RG7787 is a clinically optimized RIT consisting of a humanized anti-mesothelin Fab fused to domain III of Pseudomonas exotoxin A, in which immunogenic B-cell epitopes are silenced. To enhance the therapeutic efficacy of RITs, we conducted a kinome RNAi sensitization screen, which identified discoidin domain receptor 1 (DDR1), a collagen-activated tyrosine kinase, as a potential target. The collagen/DDR1 axis is implicated in tumor-stromal interactions and potentially affects tumor response to therapy. Therefore, we investigated the effects of DDR1 on RIT. Knockdown of DDR1 by siRNA or treatment with inhibitor, 7rh, greatly enhanced the cytotoxic activity of RG7787 in several cancer cell lines. Investigation into the mechanism of action showed DDR1 silencing was associated with decreased expression of several ribosomal proteins and enhanced inhibition of protein synthesis. Conversely, induction of DDR1 expression or collagen-stimulated DDR1 activity protected cancer cells from RG7787 killing. Moreover, the combination of RG7787 and DDR1 inhibitor caused greater shrinkage of tumor xenografts than either agent alone. These data demonstrate that DDR1 is a key modulator of RIT activity and represents a novel therapeutic strategy to improve targeting of mesothelin-expressing cancers.
Is it Possible to Reverse the Endothelial Dysfunction in Pulmonary Arterial Hypertension?⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Robyn Barst
Journal: Journal of the American College of Cardiology (2007)
Abstract 19415: Akt1 Deficiency Blocks Hypothermia Protection and Increases Plasma PBEF after Murine Sudden Cardiac Arrest
Authors: Jing Li, Huashan Wang, Sy-Jou Chen, David G Beiser, Terry L Vanden Hoek
Journal: Circulation (2014)

Introduction:  Therapeutic hypothermia protection for cardiovascular resuscitation has been related by us to enhanced nitric oxide generation and attenuated blood PBEF concentrations and related inflammation. Akt1 is a multi-organ regulator of both NOS3 and inflammation. We hypothesized that Akt1 may be critical for therapeutic hypothermia protection after murine sudden cardiac arrest (SCA).   Methods:  C57BL6 wild type (WT) and Akt1 +/-  mice underwent 8 min of KCl-induced SCA and received intra-arrest cooling to 30-32 o C at cardiopulmonary resuscitation (CPR) that was maintained until 1 h after CPR. Outcomes included mean arterial pressure (MAP), lactate clearance and 48 h survival. Tissue markers of Akt activation (Western blot phosphorylation of heart Akt, GSK3β and phospholamban) and inflammation (Western blot heart IκBα degradation and blood PBEF) were also measured.   Results:  Compared to the WT mice treated with hypothermia, 48 h survival in Akt1 +/-  mice was significantly decreased (WT 50% n=14 vs. 35% Akt1 group n=10, p    Conclusion:  Akt1 plays a critical role in mediating hypothermia protection against SCA injury. Strategies that rapidly modulate Akt activation and downstream Akt1-specific effects during CPR warrant further study.
The Best “Model System” for Human (Coronary Arteries) Is Human⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Oscar Ö. Braun, Paul A. Insel
Journal: Journal of the American College of Cardiology (2009)
Multimedia: Where Women Have No Doctor: A Health Guide for Women
Authors: H P S Sachdev
Journal: BMJ (1998)

A August Burns, Ronnie Lovich, Jane Maxwell, Katharine Shapiro


Macmillan Education (for the Hesperian Foundation), £7.25, pp 583 




ISBN 0 333 64933 8

———————

Rating: ★★★

In the industrialised nations, simplified texts have long been used to educate the public about important medical conditions. Similar reasonably priced publications are now increasingly in demand in developing countries. Of the many subjects pregnancy, birth, and infant care are evergreen favourites.

Concerned about the welfare of millions of women subsisting in areas “where there is no doctor or where health care is not afford-able,” the Hesperian Foundation has extended this concept to conceive a “self-help medical information” monograph. The stated objectives of the book are “to help women care for their own health, and to help community health workers or others meet women’s health needs” by including “information that will be useful for those with no formal training in healthcare skills, and for those who do have some training.”

Apart from reproductive health, including common obstetric emergencies, the monograph provides relevant information on nutrition, medical problems, disabilities, mental health, and social issues confronting women in underprivileged societies. The text makes easy reading with links to additional pertinent information on important topics, and is enhanced by liberal use of expressive drawings (over 1000) and incorporation of key messages.

An innovative feature is the detailed description of illustrative case studies examining the root cause of a problem and feasible solutions. These true life examples will stimulate motivated readers to initiate remedial action, including community mobilisation, in their own setting.

A large proportion of literate women should be able to comprehend the narrative. However, the sections detailing drug descriptions and healthcare skills could prove too complex for the usual target audience and thus risk inappropriate (and occasionally dangerous) application of incomplete knowledge in unsupervised settings. Interestingly, the copyright holders “do not assume liability for the use of information contained in this book.”

Self help medical information is an oversimplified and controversial method for improving the health of women in places where doctors are not available. These are precisely the areas where there is a high degree of poverty, illiteracy, and inadequate access to good health care. All these factors will seriously impede the envisaged use of the monograph even after translation and local adaptation. For example, providing information about expensive antibiotics and techniques for measuring blood pressure (without availability of instruments) seems superfluous in these settings. Future editions should distinguish between the knowledge suitable for lay women and that for paramedics.
Effectiveness of Patient Choice in Nonoperative vs Surgical Management of Pediatric Uncomplicated Acute Appendicitis
Authors: Peter C. Minneci, Justin B. Mahida, Daniel L. Lodwick, Jason P. Sulkowski, Kristine M. Nacion, Jennifer N. Cooper, Erica J. Ambeba, R. Lawrence Moss, Katherine J. Deans
Journal: JAMA Surgery (2015)

Current evidence suggests that nonoperative management of uncomplicated appendicitis is safe, but overall effectiveness is determined by combining medical outcomes with the patient's and family's perspective, goals, and expectations.To determine the effectiveness of patient choice in nonoperative vs surgical management of uncomplicated acute appendicitis in children.Prospective patient choice cohort study in patients aged 7 to 17 years with acute uncomplicated appendicitis presenting at a single pediatric tertiary acute care hospital from October 1, 2012, through March 6, 2013. Participating patients and families gave informed consent and chose between nonoperative management and urgent appendectomy.Urgent appendectomy or nonoperative management entailing at least 24 hours of inpatient observation while receiving intravenous antibiotics and, on demonstrating improvement of symptoms, completion of 10 days of treatment with oral antibiotics.The primary outcome was the 1-year success rate of nonoperative management. Successful nonoperative management was defined as not undergoing an appendectomy. Secondary outcomes included comparisons of the rates of complicated appendicitis, disability days, and health care costs between nonoperative management and surgery.A total of 102 patients were enrolled; 65 patients/families chose appendectomy (median age, 12 years; interquartile range [IQR], 9-13 years; 45 male [69.2%]) and 37 patients/families chose nonoperative management (median age, 11 years; IQR, 10-14 years; 24 male [64.9%]). Baseline characteristics were similar between the groups. The success rate of nonoperative management was 89.2% (95% CI, 74.6%-97.0%) at 30 days (33 of 37 children) and 75.7% (95% CI, 58.9%-88.2%) at 1 year (28 of 37 children). The incidence of complicated appendicitis was 2.7% in the nonoperative group (1 of 37 children) and 12.3% in the surgery group (8 of 65 children) (P = .15). After 1 year, children managed nonoperatively compared with the surgery group had fewer disability days (median [IQR], 8 [5-18] vs 21 [15-25] days, respectively; P < .001) and lower appendicitis-related health care costs (median [IQR], $4219 [$2514-$7795] vs $5029 [$4596-$5482], respectively; P = .01).When chosen by the family, nonoperative management is an effective treatment strategy for children with uncomplicated acute appendicitis, incurring less morbidity and lower costs than surgery.clinicaltrials.gov Identifier: NCT01718275.
Abstract 12627: Myocardial Infarction Alters Neural Processing of Afferent Inputs in the Intrinsic Cardiac Nervous System
Authors: Pradeep S Rajendran, Marmar Vaseghi, J Andrew Armour, Jeffrey L Ardell, Kalyanam Shivkumar
Journal: Circulation (2014)

Introduction: The intrinsic cardiac nervous system (ICNS) is an important coordinator of cardiac function and its regulatory functions can be impacted by cardiac disease. Our aim was to characterize the neural remodeling that occurs in the ICNS in response to chronic myocardial infarction (MI). Methods: Activity from intrinsic cardiac (IC) neurons in the ventral interventricular ganglionated plexus was recorded using a linear microelectrode array in 5 normal pigs and 6 pigs with chronic MI. Changes in neuron activity were evaluated in response to: (1) focal mechanotransduction (touch); transient occlusion of the (2) inferior vena cava (IVC) and (3) carotid arteries; and electrical stimulation of (4) cervical vagi and (5) stellate ganglia. Results: A total of 72 IC neurons were identified in normal pigs and 63 neurons in MI pigs. The proportion of neurons that responded to epicardial touch at the left ventricular (LV) apex (i.e. infarct zone) was significantly decreased in MI (3.2%) compared to normal (23....
Antidepressants and suicide
Authors: I. Whyte, N. Buckley, G. Carter
Journal: BMJ (1995)

populations, with variable doses and durations, which creates further difficulty in interpreting such data.We therefore conclude that it is not possible to state with certainty which of the seven most commonly prescribed non-steroidal antiinflammatory drugs is the safest; six of these seven have similar profiles of adverse events.
Designed ankyrin repeat proteins are effective targeting elements for chimeric antigen receptors
Authors: Joanne A. Hammill, Heather VanSeggelen, Christopher W. Helsen, Galina F. Denisova, Carole Evelegh, Daniela G. M. Tantalo, Jennifer D. Bassett, Jonathan L. Bramson
Journal: Journal for ImmunoTherapy of Cancer (2015)

Adoptive cell transfer of tumor-specific T lymphocytes (T cells) is proving to be an effective strategy for treating established tumors in cancer patients. One method of generating these cells is accomplished through engineering bulk T cell populations to express chimeric antigen receptors (CARs), which are specific for tumor antigens. Traditionally, these CARs are targeted against tumor antigens using single-chain antibodies (scFv). Here we describe the use of a designed ankyrin repeat protein (DARPin) as the tumor-antigen targeting domain.We prepared second generation anti-HER2 CARs that were targeted to the tumor antigen by either a DARPin or scFv. The CARs were engineered into human and murine T cells. We then compared the ability of CARs to trigger cytokine production, degranulation and cytotoxicity.The DARPin CARs displayed reduced surface expression relative to scFv CARs in murine cells but both CARs were expressed equally well on human T cells, suggesting that there may be a processing issue with the murine variants. In both the murine and human systems, the DARPin CARs were found to be highly functional, triggering cytokine and cytotoxic responses that were similar to those triggered by the scFv CARs.These findings demonstrate the utility of DARPins as CAR-targeting agents and open up an avenue for the generation of CARs with novel antigen binding attributes.
Pseudo-outbreak of Legionnaires disease among patients undergoing bronchoscopy - Arizona, 2008.
Authors: C. Kioski, K. Montefour, M. Saubolle, T. Johnson, J. Faidley, M. Williams, A. Khalsa, M. Rudinsky, C. Ogden, R. Sunenshine, L. Hicks, N. Kozak, E. Brown, M. Buss, B. Fields, M. Arduino, B. Silk, S. Chen
Journal: MMWR Morbidity and Mortality Weekly Report (2009)
Phase II study of hepatic arterial floxuridine, leucovorin, and dexamethasone for unresectable liver metastases from colorectal carcinoma.
Authors: N Kemeny, J A Conti, A Cohen, P Campana, Y Huang, W J Shi, J Botet, S Pulliam, J R Bertino
Journal: Journal of Clinical Oncology (1994)

PURPOSE To determine the toxicity, response rate, and survival of a regimen of hepatic arterial floxuridine (FUDR) with leucovorin (LV) and dexamethasone (Dec) for the treatment of unresectable hepatic metastases from colorectal carcinoma. PATIENTS AND METHODS Sixty-two patients with hepatic metastases (33 previously untreated with chemotherapy) were treated with FUDR (0.30 mg/kg/d) and LV (15 mg/m2/d) and Dec (20 mg total dose) as a 14-day hepatic arterial infusion via an implantable pump alternating with 2 weeks of saline. RESULTS The complete response (CR) plus partial response (PR) rate was 78% in previously untreated patients, with a median survival duration of 24.8 months; 1- and 2-year survival rates were 91% and 57%, respectively. In the previously treated group, the response rate was 52%, with a median survival duration of 13.5 months. Only 3% of patients (two of 62) developed biliary sclerosis; this was significantly lower than the 21% biliary sclerosis rate observed in our previous trial of hepatic arterial FUDR and LV without Dec (P = .002). CONCLUSION The addition of Dec to hepatic arterial FUDR and LV reduces biliary toxicity while maintaining an excellent response rate and survival. We recommend that this treatment be studied further.
M06-03: Prediction of benefit from EGFR TKIs by proteomic analysis of pretreatment serum
Authors: Fumiko Taguchi, Benjamin Solomon, Vanesa Gregorc, Heinrich Roder, Robert Gray, Kazuo Kasahara, Makoto Nishi, Julie Brahmer, Anna Spreafico, Vienna Ludovini, Pierre P. Massion, Rafal Dziadziuszko, Joan Schiller, Julia Grigorieva, Maxim Tsypin, Stephen W. Hunsucker, Richard Caprioli, Mark W. Duncan, Fred R. Hirsch, Paul A. Bunn, David P. Carbone
Journal: Journal of Thoracic Oncology (2007)