tbuckley/cabot-search huggingface dataset:
Introducing criteria based audit into Ugandan maternity units
Authors: A. D Weeks
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Problem</b> Maternal mortality in Uganda has remained unchanged at 500/100 000 over the past 10 years despite concerted efforts to improve the standard of maternity care. It is especially difficult to improve standards in rural areas, where there is little money for improvements. Furthermore, staff may be isolated, poorly paid, disempowered, lacking in morale, and have few skills to bring about change. <b>Design</b> Training programme to introduce criteria based audit into rural Uganda. <b>Setting</b> Makerere University Medical School, Mulago Hospital (large government teaching hospital in Kampala), and Mpigi District (rural area with 10 small health centres around a district hospital). <b>Strategies for change</b> Didactic teaching about criteria based audit followed by practical work in own units, with ongoing support and follow up workshops. <b>Effects of change</b> Improvements were seen in many standards of care. Staff showed universal enthusiasm for the training; many staff produced simple, cost-free improvements in their standard of care. <b>Lessons learnt</b> Teaching of criteria based audit to those providing health care in developing countries can produce low cost improvements in the standards of care. Because the method is simple and can be used to provide improvements even without new funding, it has the potential to produce sustainable and cost effective changes in the standard of health care. Follow up is needed to prevent a waning of enthusiasm with time.
Reply to: “Regarding trichoscopy of dissecting cellulitis of the scalp”
Authors: Gonzalo Segurado-Miravalles, Francisco Camacho-Martínez, Salvador Arias-Santiago, Rita Rodrigues-Barata, Cristina Serrano-Falcón, Oscar Muñoz Moreno-Arrones, Pedro Jaén Olasolo, Sergio Vañó-Galván
Journal: Journal of the American Academy of Dermatology (2017)
Prognostic Significance of 11q23/MLL Fusion Partners in Children with Acute Myeloid Leukemia (AML) - Results from the Children's Oncology Group (COG) Trial AAML0531
Authors: Erin M. Guest, Betsy A. Hirsch, E. Anders Kolb, Todd A. Alonzo, Robert Gerbing, Richard Aplenc, Jessica Pollard, Lillian Sung, Soheil Meshinchi, Alan S. Gamis, Susana C. Raimondi
Journal: Blood (2016)
PMO-142 Evidence refuting the Trojan-horse hypothesis of brain swelling in acute liver failure: l-type glutaminase is exclusively neuronal: Abstract PMO-142 Figure 1
Authors: Y Sharifi, N Shah, M Jover, D Marsdon, N Davies, F Scaravilli, R Jalan
Journal: Gut (2012)

<h3>Introduction</h3> Astrocytic swelling is the characteristic feature of hyperammonemia and acute liver failure (ALF) which is thought to result from accumulation of glutamine due to the action of astrocytic glutamine synthetase (GS). It has been suggested that glutamine may not be a benign amino acid and may act as “Trojan horse” which leads to astrocytic apoptosis as it is metabolised by Glutaminase (GLN) yielding glutamate and ammonia. In vivo proof for this hypothesis is lacking. In health, GLN is mainly neuronal and generates glutamate and GABA. The aims of the study were to define the expression of the ammonia metabolising enzymes, GS and GLN in the brain of ALF animals. <h3>Methods</h3> Two groups of CD1 mice were studied, sham: n=6; paracetamol (500 mg/kg IP): n=7. The animals were maintained normothermic and resuscitated with fluid and glucose and sacrificed at 8 h after injection of APAP or before development of coma. Arterial ammonia (COBAS) and frontal cortex brain water (dry weight technique) were measured. The brain sections were stained for GS and K and L-type GLN. <h3>Results</h3> Arterial ammonia was significantly higher in the ALF group compared with controls (345±32 vs 132±11 p=0.002) and brain water did not reach significance (83.6±2.3 vs 76.3±2.6 p=0.05). GS protein expression was observed in the astrocytes in the dentate fascia in both groups and was not different but was also seen in the oligodendrocytes only in ALF group. L-type GLN was expressed only in the neurons and not in the astrocytes and was significantly higher in the ALF animals (++++) compared with controls (+). The most marked areas were the striatum and dentate fascia and interestingly the staining was mainly cytoplasmic. K-type GLN was not different between groups and limited to brain capillaries. <h3>Conclusion</h3> Conclusion: The results of this study refute the Trojan-horse hypothesis and show for the first time increased protein expression of L-type GLN which is exclusively neuronal. From the pathophysiological perspective, this may function to generate excessive ammonia in the neuron thereby producing neuronal cell death. <h3>Competing interests</h3> None declared.
Open-label, multicenter, single-arm, phase I, dose-dscalation with efficacy tail extension study of vemurafenib in pediatric patients with surgically incurable and unresectable stage IIIc or IV melanoma harboring <i>BRAF<sup>V600</sup></i> mutations (NCT01519323).
Authors: Fariba Navid, Julia C. Chisholm, Andrea Ferrari, Cynthia E. Herzog, Carlos Rodriguez-Galindo, Axel Hauschild, Kartik Krishnan, Alberto S. Pappo
Journal: Journal of Clinical Oncology (2013)

TPS9104 Background: Although rare, melanoma is the most common form of skin cancer in children and the incidence is rising in the adolescent population. Similar to adults, the outcome for pediatric patients with advanced or recurrent melanoma is poor. Many adult studies of melanoma exclude patients under the age of 18 years. Approximately 50% of melanomas carry a mutation in the BRAF gene and the oral BRAF inhibitor vemurafenib (VEM) has demonstrated improved rates of overall and progression-free survival in adult melanoma patients who carry this mutation (Chapman et al; NEJM 2011). The current study is designed to determine the maximum tolerated dose (MTD)/recommended dose (RD), pharmacokinetics, safety, tolerability, and efficacy of VEM in pediatric patients with surgically incurable and unresectable stage IIIC/IV melanoma harboring BRAF V600 mutations. Methods: Patients aged 12 through 17 years with newly diagnosed or previously treated measurable disease are eligible. Patients with radiographically stable, asymptomatic previously treated central nervous system lesions are also eligible. In the dose-escalation phase, patients will be enrolled sequentially to increasing dose cohorts of VEM following a 3+3 design. Dose-limiting toxicity will be assessed during the first cycle (defined as the first 28 days). The initial dose will be 720 mg BID (patients ≥45 kg) or 480 mg BID (patients &lt;45 kg). Once the MTD/RD for the extension phase is defined based on the dose-escalation window, all patients will be eligible to receive the MTD/RD. The efficacy tail of the trial will enroll additional pediatric patients at the MTD/RD. Patients will receive VEM until disease progression, death, unacceptable tolerability, discontinuation from the study, or other protocol-specified criteria. The study aims to treat approximately 20 patients at the RD with 3-15 additional patients treated at other dose levels during the dose-escalation phase. This study is currently open at 18 sites in the USA, UK, Germany, Italy, and Australia. As of January 24, 2013, one patient has been enrolled. Clinical trial information: NCT01519323.
Cell-based assays suggest role for RAB11FIP1 in cell cycle and apoptosis
Authors: Wan Yee Leong, Fu Ling Soh, Bing Ling Han, Fui Leng Yan, Lance Miller, Christopher Wong
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

1847 

RAB11FIP1 is one of several potential oncogenes located in the chromosome 8p11 amplicon which is amplified in 10-15% of human breast cancers (1, 2). It is over-expressed in a panel of breast cancer cell lines but not in MCF10A, a non-tumorigenic human breast epithelial cell line. However, its functions and mechanisms of action are not well characterized. We knocked down RAB11FIP1 with siRNA in a panel of cancer cell lines and observed significantly reduced cell viability. Data from cell-based assays suggest that this reduction in cell viability is caused by 2 mechanisms: increased apoptosis and cell cycle arrest at G2. Increased apoptosis was demonstrated by increased activation of Caspase 3, FOXO3a, PARP cleavage and nuclear condensation across a panel of breast and colon cancer cell lines. Knockdown of RAB11FIP1 also made cells more susceptible to SAHA-induced apoptosis, requiring a lower dose than wild-type cells. In addition, we observed increased activation of p53 and p21 in cells where RAB11FIP1 was knocked down, resulting in G2 arrest. Treatment with SAHA enhanced the p53 and p21 activation in a dose-dependent manner. While wild-type p53 was required for cell cycle arrest induced by RAB11FIP1 knock-down, it was not required for apoptosis induced by RAB11FIP1 knock-down, although presence of wild-type p53 enhanced the apoptotic response. In this paper, we will describe the pathways modulated by RAB11FIP1 and provide evidence supporting its candidacy as an oncogene.    References:    1. Yang, Z. Q., Streicher, K. L., Ray, M. E., Abrams, J., and Ethier, S. P. Multiple interacting oncogenes on the 8p11-p12 amplicon in human breast cancer. Cancer Res, 66: 11632-11643, 2006.    2. Garcia, M. J., Pole, J. C., Chin, S. F., Teschendorff, A., Naderi, A., Ozdag, H., Vias, M., Kranjac, T., Subkhankulova, T., Paish, C., Ellis, I., Brenton, J. D., Edwards, P. A., and Caldas, C. A 1 Mb minimal amplicon at 8p11-12 in breast cancer identifies new candidate oncogenes. Oncogene, 24: 5235-5245, 2005.
Spontaneous splenic rupture as the initial presentation of plasma cell leukemia: a case report
Authors: Celalettin Üstün, Cem Sungur, Oral Akbaş, Arzu Sungur, Yücel Gürgen, Şevket Ruacan, Günhan Gürman, Önder Arslan
Journal: American Journal of Hematology (1998)

lymph node involvement with rt ureter compression that required a stent insertion.Brain CT showed a suprasellar lesion involving the diencephalic and chiasmatic regions (Fig. 1a).The patient was treated with CdA (2 hr-infusion of 0.14 mg/kg die × 7 days) and Dexamethasone (0.3 mg/kg die × 4 days).Therapy was well tolerated without significant hematologic toxicity (WHO G4 leukopenia duration, 3 days; no thrombocytopenia).Partial regression of the liver, kidney, and lymph node involvement and complete regression of the brain lesions (Fig. 1b) were documented 1 month later by CT.The patient was discharged on May 24 with complete regression of the neurological symptoms.On June 13 she died from an acute cerebral vascular accident (CVA) of ischemic origin (brain CT not shown).In this patient, a single cycle of CdA induced complete regression of the brain lesion.CVA as a complication of therapy with CdA has not been reported; a relationship between treatment and the final event is unlikely.
Is Atherosclerosis in Diabetes and Impaired Fasting Glucose Driven by Elevated LDL Cholesterol or by Decreased HDL Cholesterol?
Authors: Heinz Drexel, Stefan Aczel, Thomas Marte, Werner Benzer, Peter Langer, Willi Moll, Christoph H. Saely
Journal: Diabetes Care (2005)

Our study (1) demonstrates that an LDL-related lipid factor in coronary patients with type 2 diabetes is 1 ) not elevated, 2 ) not associated with significant coronary stenoses, and 3 ) not significantly predictive for future events. Whereas the first two findings did not even show a trend for the LDL-related factor, our prospective data need to be confirmed by a longer follow-up with more end points. We have …
Broad Spectrum Macromolecular Antimicrobials with Biofilm Disruption Capability and In Vivo Efficacy
Authors: Jeremy P. K. Tan, Daniel J. Coady, Haritz Sardon, Alexander Yuen, Shujun Gao, Shaun W. Lim, Zhen Chang Liang, Eddy W. Tan, Shrinivas Venkataraman, Amanda C. Engler, Mareva Fevre, Robert Ono, Yi Yan Yang, James L. Hedrick
Journal: Advanced Healthcare Materials (2017)

In this study, antimicrobial polymers are synthesized by the organocatalytic ring-opening polymerization of an eight-membered heterocyclic carbonate monomer that is subsequently quaternized with methyl iodide. These polymers demonstrate activity against clinically relevant Gram-positive Staphylococcus epidermidis and Staphylococcus aureus, Gram-negative Escherichia coli and Pseudomonas aeruginosa, and fungus Candida albicans with fast killing kinetics. Importantly, the polymer efficiently inhibits biofilm growth and lyses existing biofilm, leading to a reduction in biomass and cell viability. In addition, the macromolecular antimicrobial is less likely to induce resistance as it acts via a membrane-lytic mechanism. The polymer is not cytotoxic toward mammalian cells with LD50 of 99.0 ± 11.6 mg kg-1 in mice through i.v. injection. In an S. aureus blood stream infection mouse model, the polymer removes bacteria from the blood more rapidly than the antibiotic Augmentin. At the effective dose, the polymer treatment does not damage liver and kidney tissues or functions. In addition, blood electrolyte balance remains unchanged after the treatment. The low cost of starting materials, ease of synthesis, nontoxicity, broad spectrum activity with fast killing kinetics, and in vivo antimicrobial activity make these macromolecular antimicrobials ideal candidates for prevention of sepsis and treatment of infections.
Angiotensin II for the Treatment of Vasodilatory Shock
Authors: Ashish Khanna, Shane W. English, Xueyuan S. Wang, Kealy Ham, James Tumlin, Harold Szerlip, Laurence W. Busse, Laith Altaweel, Timothy E. Albertson, Caleb Mackey, Michael T. McCurdy, David W. Boldt, Stefan Chock, Paul J. Young, Kenneth Krell, Richard G. Wunderink, Marlies Ostermann, Raghavan Murugan, Michelle N. Gong, Rakshit Panwar, Johanna Hästbacka, Raphael Favory, Balasubramanian Venkatesh, B. Taylor Thompson, Rinaldo Bellomo, Jeffrey Jensen, Stew Kroll, Lakhmir S. Chawla, George F. Tidmarsh, Adam M. Deane
Journal: New England Journal of Medicine (2017)

Vasodilatory shock that does not respond to high-dose vasopressors is associated with high mortality. We investigated the effectiveness of angiotensin II for the treatment of patients with this condition.We randomly assigned patients with vasodilatory shock who were receiving more than 0.2 μg of norepinephrine per kilogram of body weight per minute or the equivalent dose of another vasopressor to receive infusions of either angiotensin II or placebo. The primary end point was a response with respect to mean arterial pressure at hour 3 after the start of infusion, with response defined as an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors.A total of 344 patients were assigned to one of the two regimens; 321 received a study intervention (163 received angiotensin II, and 158 received placebo) and were included in the analysis. The primary end point was reached by more patients in the angiotensin II group (114 of 163 patients, 69.9%) than in the placebo group (37 of 158 patients, 23.4%) (odds ratio, 7.95; 95% confidence interval [CI], 4.76 to 13.3; P<0.001). At 48 hours, the mean improvement in the cardiovascular Sequential Organ Failure Assessment (SOFA) score (scores range from 0 to 4, with higher scores indicating more severe dysfunction) was greater in the angiotensin II group than in the placebo group (-1.75 vs. -1.28, P=0.01). Serious adverse events were reported in 60.7% of the patients in the angiotensin II group and in 67.1% in the placebo group. Death by day 28 occurred in 75 of 163 patients (46%) in the angiotensin II group and in 85 of 158 patients (54%) in the placebo group (hazard ratio, 0.78; 95% CI, 0.57 to 1.07; P=0.12).Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors. (Funded by La Jolla Pharmaceutical Company; ATHOS-3 ClinicalTrials.gov number, NCT02338843 .).
First European phase II trial of intravenous (iv) cetuximab (Cet) and hepatic artery infusion (HAI) of irinotecan, 5-fluorouracil and oxaliplatin in patients with unresectable liver metastases from <i>wt</i> KRAS colorectal cancer (CRC) after systemic therapy failure (OPTILIV, NCT00852228).
Authors: Francis Levi, Michel Ducreux, Mohamed Hebbar, Philippe Rougier, C. N. J. Focan, Rosine Guimbaud, Carlos Carvalho, Salvatore Tumolo, Pasquale F. Innominato, Yves Ajavon, Denis Castaing, Thierry De Baere, Abdoulaye Karaboué, Celine Lepere, Valerie Boige, Laetitia Proux, Rene Adam, Mohamed Bouchahda
Journal: Journal of Clinical Oncology (2012)

3547 Background: HAI of chronomodulated (Chrono) irinotecan (I), 5-Fluorouracil (F) and oxaliplatin (O), or flat O combined with iv F-leucovorin allowed secondary metastases resections and prolonged survival in patients (pts) with CRC liver metastases despite prior chemotherapy failure (Bouchahda, Cancer 2009; Goere, Ann Surg 2010). Purpose: To prospectively evaluate safety and efficacy of combining iv Cet with HAI of IFO in pts with CRC liver metastases. Methods: This Phase II trial involved previously treated pts with unresectable CRC liver metastases. Pts received iv Cet (500 mg/m²) and Chrono or conventional HAI of I (180 mg/m²), F (2800 mg/m²), and O (85 mg/m²) q2 weeks. Liver metastases were resected if adequately downstaged. Results: Planned accrual of 60 pts was reached on 01/24/2012. 3 pts were not treated, 9 are ongoing. 48 consecutive treated pts (18F, 30 M; aged 32-76 years) are fully assessed and monitored. They had PS 0-1 (98%), bilobar liver lesions (69%), a median of 8 metastases (1-50; largest diameter, 57 mm – 15-172). Prior chemotherapy involved one (43%), or two or three (57%) lines. A median of 5 protocol courses (1-13) was given. Main grade 3-4 toxicities per pt were neutropenia (40%), abdominal pain (15%), fatigue (15%), nausea (15%), diarrhea (13%) and sensory neuropathy (4%). Objective response rate was 44% [30-58], with 6% radiological complete responses. Disease control rate was 85%. Secondary liver surgery was performed in 15 pts (31.3%).One pt with 25 metastases (1-6 cm) in all liver segments had pathologic complete response in 24 lesions removed through three-stage hepatectomy. She currently has an off treatment disease-free survival of 17+ months.With a follow up of 4 to 47 months, median progression-free survival is 14.2 months [9.7-18.8], 1- and 2-year survival rates are 92.8% and 59.2% respectively. Conclusions: OPTILIV offers a safe and unusually effective treatment option for patients with CRC liver metastases after failure of systemic chemotherapy within a coordinated medico-surgical strategy.
Hepatic sinusoidal endothelium heterogeneity with respect to mannose receptor activity is interleukin-1 dependent
Authors: A Asumendi, A Alvarez, I Martinez, B Smedsrød, F Vidal-Vanaclocha
Journal: Hepatology (1996)

Using fluorescein isothiocyanate–conjugated ovalbumin (OVA–FITC), 125I–mannan, or 125I–invertase as specific ligands for the mannose receptor, we have quantified its activity in mouse and rat hepatic sinusoidal endothelium (HSE), under both basal conditions and after lipopolysaccharide (LPS) or human recombinant interleukin–1β (IL–1β) stimulations. Mouse treatment for 4 hours with 5 μg/kg IL–1β significantly increased OVA–FITC uptake by HSE. Ligand uptake exhibited a sublobular compartmentalization: In control mice as well as in IL–1β–stimulated mice, the ligand distributed preferentially in the periportal and septal areas; no OVA–FITC was observed in the perivenous sinusoids. In vitro exposure of mouse HSE to 100 pg/mL LPS or 1 ng/mL IL–1β for 6 hours significantly ( P &lt; .01) increased OVA–FITC uptake. Blocking IL–1 receptors in HSE by addition of 100 ng/mL IL–1 receptor antagonist (IL–1Ra) before stimulation with LPS or IL–1β abrogated the increase in mannose receptor–mediated uptake. In vitro endocytosis assays showed that rat HSE uptake of 125I–mannan or 125I–invertase progressively increased with both exposure time and concentration of added IL–1β. Upregulation of mannose receptor–mediated uptake in response to IL–1β or LPS was also blocked by previous addition of IL–1Ra to rat HSE. Flow cytometric analysis showed a significant HSE heterogeneity in mannose receptor–mediated endocytosis in response to IL–1β treatment: type I endothelial cells (EC–I, defined by their small size and high cytoplasmic density) significantly ( P &lt; .01) increased OVA–FITC uptake compared with type II endothelial cells (EC–II, defined by their large size and low cytoplasmic density). In addition, the subset of EC–I contained three times more IL–1β–binding cells than the EC–II subset. Because EC–I and EC–II are preferentially located in the periportal and perivenous segments of hepatic sinusoids, respectively, these results suggest that IL–1β, apart from upregulating mannose receptor activity, contributes to the sublobular compartmentalization of this endothelial cell function.
Comparison of concurrent use of carboplatin-Paclitaxel versus cisplatin-etoposide with thoracic radiation for stage III NSCLC patients: A systematic review.
Authors: Conor Ernst Steuer, Madhusmita Behera, Kristin Ann Higgins, Nabil F. Saba, Dong Moon Shin, Suchita Pakkala, Rathi Narayana Pillai, Taofeek Kunle Owonikoko, Walter John Curran, Chandra Prakash Belani, Fadlo Raja Khuri, Suresh S. Ramalingam
Journal: Journal of Clinical Oncology (2015)

7536 Background: The two most commonly used chemotherapy regimens deployed concurrently with thoracic radiation (RT) for patients with unresectable IIIA and IIIB non-small cell lung cancer (NSCLC) are carboplatin/paclitaxel (CP) and cisplatin/etoposide (CE). Because there are no prospective comparisons of these two regimens in this setting, we conducted a systematic review of published trials to compare outcomes and toxicities between CE and CP. Methods: Studies which enrolled stage III patients receiving RT with CP or CE were identified using electronic databases (MEDLINE, EMBASE, and Cochrane library) and meeting abstracts. Trials were excluded if they were phase I, enrolled less than 10 pts, or included surgical resection. A systematic analysis of extracted data was performed using Comprehensive Meta Analysis (Version 2.2) software using random and fixed effect models. Clinical outcomes were compared using point estimates for weighted values of median overall survival (OS), progression free survival (PFS), response rate (RR) and toxicities. Two-tailed T-test with a significance level of 0.05 was used for all comparisons. Results: 3194 patients were included from 32 studies in the CE arm, and 3789 patients from 51 studies in CP. Baseline characteristics of patients on the CE arm versus CP arm were: median age 61 vs. 63 years, male 67.6% vs. 78%, squamous histology 39% vs. 40%, and median radiation dose 62 Gy vs. 63 Gy. There was no significant difference in response rates between CE and CP (65% vs. 56%, p = 0.6), respectively. There was no significant difference in median progression free survival (11.5m vs. 9.3m p = 0.2), overall survival (19.8m vs. 18.4m, p = 0.48), or 3-year survival rate (31% vs. 25%, p = 0.4) for CE vs. CP. CE was associated with higher grade 3/4 hematological toxicities than CP, such as neutropenia (53% vs. 23% p < 0.0001), as well as grade 3/4 nausea/vomiting (20% vs. 9% p = 0.018), while rates of grade 3/4 pneumonitis and esophagitis were similar. Conclusions: CE and CP regimens were associated with comparable efficacy when used with concurrent radiotherapy for stage III unresectable NSCLC pts. The toxicity profile favored the CP regimen.