tbuckley/cabot-search huggingface dataset:
Toxicities in a phase II study of accelerated high dose thoracic radiation therapy (TRT) with concurrent chemotherapy for limited small cell lung cancer (LSCLC) (RTOG 0239)
Authors: R. Komaki, J. Moughan, D. Ettinger, G. Videtic, J. Bradley, B. Glisson, H. Choy
Journal: Journal of Clinical Oncology (2007)

7717 Background: Accelerated fractionation proved beneficial in INT0096, but the total dose was low and local recurrence was high with higher acute grade (Gr.) 3+ esophagitis. RTOG 0239 was a phase II trial to improve local control and survival with LSCLC with acceptable acute Gr. 3+ esophagitis using accelerated high dose TRT and concurrent cisplatin/etoposide. This is the first report of acute Gr.3+ esophagitis and Gr.5 toxicities. Methods: Patients (pts) with LSCLC without pleural effusion, contralateral hilar or contralateral supraclavicular nodes and PS 0–1 were enrolled. TRT was given to large fields to 28.8 Gy at 1.8 Gy per fraction, 5 days per week for 16 fractions followed by BID with large field in AM, boost in PM, then off-cord boost BID for last 5 days, all at 1.8 Gy per fx for a total dose of 61.2 Gy in 34 fx in 5 weeks. Concurrent chemotherapy was started with TRT with cisplatin, 60 mg/m 2 i.v. day 1; etoposide, 120 mg/m 2 i.v. day 1; etoposide, 240 mg/m 2 p.o. per day or 120 mg/m 2 i.v. per day on days 2 or 3. Cycles were repeated q.3 wks during and for 2 cycles after TRT. Pts who have achieved complete response one month after completion of 4 cycles of chemotherapy were asked to participate in a prophylactic cranial irradiation (PCI) study. Common toxicity criteria (CTC) 2.0 was used for acute toxicity. Results: From 10/2003 to 5/2006, 72 pts were accrued. Median age was 63 yrs with 52% females. Survival data is still maturing. Acute toxicity information is available for 68 pts. Eleven pts (16%) experienced acute Gr. 3 and 1 pt (1%) had acute Gr. 4 esophagitis. 47 pts (69%) had grade 4 blood/bone marrow toxicities. There were 2 (3%) Gr. 5 toxicities reported [1 infection with neutropenia; 1 pulmonary (pneumonia)]. Conclusions: This accelerated high dose TRT with concurrent chemotherapy for LSCLC resulted in 17% acute Gr.3+ esophagitis compared to 27% with BID TRT with 45Gy in 3 weeks by INT0096. There were 3% grade 5 toxicities. This preliminary report suggests that RTOG-0239 has tolerable toxicity. The acute Gr3+ esophageal toxicity correlated with V20 and V40 will be presented. Pts continue to be followed for the primary endpoint of 2-year survival. No significant financial relationships to disclose.
Abstract 168: Effect of Cardiopulmonary Resuscitation on Restoration of Myocardial ATP in Prolonged Ventricular Fibrillation
Authors: Han Joo Choi, Tuyet Nguyen, Kyung Cheol Cha, Hyun Kim, Kang Hyun Lee, Kyu Sang Park, Sung Oh Hwang
Journal: Circulation (2010)

Background: It is known that a short period of cardiopulmonary resuscitation (CPR) prior to defibrillation improves survival in patients with unwitnessed sudden collapse. However, there has been no report about whether CPR restores myocardial ATP during prolonged ventricular fibrillation (VF). The aim of this study is to investigate the effect of CPR on restoration of myocardial high energy phosphate in prolonged VF. Methods and Results: Seventy two adult male Sprague-Dawley rats (330–400 g) were enrolled in the study. Baseline ATP and ADP prior to induction of VF were measured from 9 animals. Sixty three animals were subjected to 4 minutes of untreated VF. Then, animals were randomized into no-CPR group (n=37) and CPR group (n=26). In no-CPR group, ATPs and ADPs were measured 4 (n=9), 6 (n=10), 8 (n=8), and 10 (n=10) minutes after induction of VF, respectively. CPR group received 2 (n=10), 4 (n=8), and 6 (n=8) minutes of mechanical chest compressions, respectively. Baseline myocardial ATP (nmol/mg pr...
Intractable Trigeminal Neuralgia
Authors: P G Watts
Journal: Journal of the Royal Society of Medicine (1987)

In 49 cases of trigeminal neuralgia seen at the Abingdon Pain Relief Unit, Oxfordshire, the average time between initial onset of pain and first referral to the unit was 9.8 years. The pattern of presentation and distribution was no different from previously published studies, indicating that the more intractable cases cannot be predicted at first presentation.
Resistive breathing aggravates endotoxin-induced lung inflammation
Authors: Constantinos Glynos, Dimitris Toumpanakis, Constantinos Loverdos, Vassiliki Karavana, Christina Magkou, Athanasia Pavlidou, Andreas Papapetropoulos, Theodoros Vassilakopoulos
Journal: European Respiratory Journal (2014)

Introduction:  During exacerbations of obstructive lung diseases, inflammation and the accompanying bronchoconstriction lead to significant airway narrowing, i.e. resistive breathing (RB). In order to distinguish between the effects of the mechanical stressor and the underlying inflammation we developed a RB model via tracheal banding (TB), and investigated the effects of RB in mice with pre-existing lung inflammationinduced by endotoxin inhalation. Since smooth muscle tone is a crucial determinant of bronchoconstriction and involves nitric oxide (NO) signaling through soluble guanylyl cyclase (sGC) activation, the expression of sGC was studied.  Materials and Methods:  Adult C57BL/6 mice underwent resistive breathing for 24 hours by placing a nylon band around the extrathoracic trachea, providing a 50% tracheal occlusion. The following groups were studied: 1. TB mice and quietly breathing sham operated mice (controls) 2. Mice treated with inhaled lipopolysaccharide (LPS) pseudomonas aeruginosa 10mg/3ml via nebulization and controls. 3. Mice treated with LPS 24 hours prior TB. Mice were sacrificed 24h post operation.  Results:  Mice subjected to resistive breathing via TB, exhibited a more pronounced increase in bronchoalveolar lavage fluid cellularity and protein content compared with mice treated with LPS alone. By using forced oscillation technique, TB further increased tissue elasticity and airway resistance. The most pronounced decrease in the expression of sGCα1 and β1 subunits was observed in the group subjected to LPS inhalation and TB.  Conclusion:  TB aggravates pre-existing lung inflammation and sGC downregulation implicating new insights into the mechanisms during obstructive lung disease exacerbations.
A Case Report of Unresectable Cutaneous Squamous Cell Carcinoma Responsive to Pembrolizumab, a Programmed Cell Death Protein 1 Inhibitor
Authors: Anne Lynn S. Chang, Jinah Kim, Richard Luciano, Loretta Sullivan-Chang, Alexander D. Colevas
Journal: JAMA Dermatology (2015)

At 1-month follow-up, the skin lesions had partially resolved, and resolution was greater by 2 months (Figure 1B).
ADENOSINE 3' 5'-CYCLIC MONOPHOSPHATE PHOSPHODIESTERASE IN SKIN.
Authors: S. W. J. HOLLA, E. P. M. J. HOLLMAN, P. D. MIER, W. J. B. M. STAAK, E. URSELMANN, J. A. WARNDORFF
Journal: British Journal of Dermatology (1972)

Summary.— The activity of cAMP phosphodiesterase under conditions of substrate saturation (Vmax) and its substrate affinity (Km) were measured in biopsy specimens from the lesions of atopic dermatitis, from atopic uninvolved skin, and from the skin of healthy controls. No significant difference was found between the atopic and the control specimens.
Pathogenic Role of <i>Bacillus Cereus</i> in Wound Infections in the Tropics
Authors: M S Dryden
Journal: Journal of the Royal Society of Medicine (1987)

A bacteriological survey was undertaken on clinically infected traumatic wounds amongst a group of young and fit Operation Raleigh members, who were living and working in a remote area of Costa Rican rain forest. All infected wounds were swabbed before treatment and, where possible, at intervals during treatment. Swabs were also obtained from the nose and throat of each patient. All swabs were stored by desiccation in sterile silica gel for culture at a later date. Culture revealed a high rate of isolation of Bacillus cereus from the wounds. The organism was commonly isolated in pure and heavy growth. Contamination by B. cereus was considered and excluded experimentally. Preliminary toxological studies have shown that the majority of the isolates produce a necrotic exotoxin, in keeping with the clinical findings. These results suggest that B. cereus caused significant sepsis in this series of traumatic wounds.
Factors determining duration of hospital stay in patients hospitalized for acute COPD exacerbation
Authors: Filia Diamantea, Stamatina Tsikrika, Foteini Karakontaki, Dimitrios Mitromaras, Eleni Stagaki, Emmanouil Kastanakis, Vlasis Polychronopoulos
Journal: European Respiratory Journal (2011)

Background:  Factors associated with the length of hospitalization in patients admitted for acute exacerbation of COPD (AECOPD) have not been thoroughly evaluated.   Objectives:  To evaluate the association between clinical and functional parameters and duration of hospital stay of patients admitted due to an AECOPD.   Methods:  We studied prospectively 31 patients (20 men, 11 women), mean age 69.5 (±7.8) years, admitted to hospital for AECOPD. Pulmonary function tests including body box evaluation of lung volumes, Borg dyspnea score at rest, Visual analogue scale dyspnea score, 6 minute walking test (6 MWT), Chronic Respiratory Questionnaire (CRQ) total and 4 domains scores, Charlson index for comorbidities, blood gases on admission, were all parameters evaluated within 72h of admission. Frequency of exacerbations, long term oxygen therapy (LTOT) prior to admission and duration of hospital stay were also recorded.   Results:  Mean duration of hospital stay was 8 days. Patients divided in 2 groups: (group 1 (18 patients): duration of stay    Conclusions:  Functional impairment and dyspnea in patients admitted for AECOPD have significant impact on the duration of their hospital recovery.
Abstract 1547: From Novice to Expert: Confidence and Activity Status Determine Heart Failure Self-Care Performance
Authors: Barbara Riegel, Christopher S Lee, Misook Chung, Nancy Albert, Terry Lennie, Eun Kyeung Song, Brooke Bentley, Linda Worrall-Carter, Seongkum Heo, Debra K Moser
Journal: Circulation (2009)
AZD5069: Pharmacological profile of a CXCR2 antagonist in development for the treatment of respiratory disorders
Authors: Carina Kärrman Mårdh, David Nicholls, Ian Dainty, Caroline Phillips, Fraser McIntosh
Journal: European Respiratory Journal (2014)

Background: Neutrophil-driven inflammation is a key component in inadequately controlled asthma, COPD and bronchiectasis. Neutrophil migration into the lung is predominantly controlled by C-X-C chemokine receptor 2 (CXCR2). AZD5069 is a reversible oral CXCR2 antagonist which is under evaluation in inadequately controlled asthma.

Methods: The affinity of AZD5069 for CXCR2 and CXCR1 was determined using membranes from HEK293 cells transfected with human recombinant CXCR2 or CXCR1 and a radiolabelled endogenous ligand [I125] CXCL8. The antagonist potency of AZD5069 was also assessed in cell systems, using either CXCL8 or CXCL1 to activate the receptor, quantifying changes in intracellular calcium, CD11b expression and chemotaxis. A rat model of pulmonary inflammation with neutrophilia induced by lipopolysaccharide (LPS) was used to investigate AZD5069 efficacy in vivo .

Results: AZD5069 demonstrated high affinity for human recombinant CXCR2 (pIC50 9.1 ± 0.05), a lower affinity for CXCR1 (pIC50 6.9 ± 0.08), potent antagonism of CXCR2-mediated calcium mobilization (pA2 = 9.6 ± 0.1), chemotaxis (pA2 = 9.6) and dose-dependent inhibition of adhesion molecule expression in whole blood. Reversibility was clearly demonstrated by displacement of radiolabelled AZD5069 from CXCR2. In addition, return of CXCR2 activity was shown following removal of AZD5069 from cells. In the LPS in vivo rat model of pulmonary inflammation, oral administration of AZD5069 produced a dose-dependent decrease in lung neutrophilia.

Conclusions: AZD5069 is a potent, reversible and selective CXCR2 antagonist that has potential as a new treatment approach for neutrophil driven inflammatory respiratory disorders.
Phase II double-blind, randomized study of selumetinib (SEL) plus docetaxel (DOC) versus DOC plus placebo as second-line treatment for advanced <i>KRAS </i>mutant non-small cell lung cancer (NSCLC).
Authors: Pasi A. Janne, Alice Tsang Shaw, Jose Rodrigues Pereira, Gaelle Jeannin, Johan Vansteenkiste, Carlos H. Barrios, Fabio A. Franke, Lynda Grinsted, Paul D. Smith, Victoria Zazulina, Ian C. Smith, Lucio Crino
Journal: Journal of Clinical Oncology (2012)

7503 Background: KRAS mutations are the most common (~20%) oncogenic alteration in NSCLC. There are no effective targeted therapies for this subset of NSCLC. Selumetinib (AZD6244, ARRY-142866) inhibits MEK1/2 signaling downstream of KRAS. We prospectively evaluated SEL + DOC vs DOC + placebo in advanced KRAS mutant NSCLC based on preclinical observations (NCT00890825). Methods: Patients (pts) with stage IIIB-IV, KRAS mutant NSCLC, who had received prior chemotherapy, received iv DOC 75 mg/m 2 , and po SEL 75 mg or placebo BD. The primary endpoint was overall survival (OS); secondary endpoints included: progression-free survival (PFS), objective response rate (RR), duration of response, change in tumor size, proportion of patients alive and progression-free at 6 mo, and safety and tolerability. Results: Between April 2009 and June 2010, 422 pts were screened across 67 centers in 12 countries; 113 had KRAS mutant NSCLC and 87 were randomized (DOC, 43; SEL/DOC, 44). Baseline characteristics were balanced (DOC vs SEL/DOC): WHO PS 0, 49%/48%; Female, 54%/52%; KRAS codon 12, 90%/93%. Median number of cycles: DOC, 4; SEL/DOC, 5. Most frequent grade 3/4 hematologic toxicity (DOC vs SEL/DOC): neutropenia (54.8%/67.4%), febrile neutropenia (0%/15.9%); most frequent grade 3/4 non-hematologic toxicity: dyspnea (11.9%/2.3%) asthenia (0%/9.1%), respiratory failure (4.8%/6.8%), acneiform dermatitis (0%/6.8%). Discontinuation due to AEs was similar: 18.2% SEL/DOC vs 11.9% DOC. OS was longer for SEL/DOC vs DOC (9.4 mo vs 5.2 mo; 56 events, median follow-up 219 days) but did not reach statistical significance; hazards were non proportional (HR 0.80; 80% CI 0.56, 1.14; 1-sided p=0.2069). All secondary endpoints, including RR (DOC 0%, SEL/DOC 37%; p&lt;0.0001) and PFS (DOC 2.1 mo, SEL/DOC 5.3 mo; 71 events; HR = 0.58; 80% CI 0.42, 0.79; 1-sided p=0.0138), were significantly improved for SEL/DOC vs DOC. Conclusions: This is the first prospective study to demonstrate a clinical benefit of a targeted therapy (SEL + DOC) for patients with KRAS mutant cancer of any type. Our findings could have implications for the treatment of NSCLC and other KRAS mutant cancers.
Low rates of breast feeding in India require national action, says report
Authors: Cheryl Travasso
Journal: BMJ (2015)

India should monitor and prioritise breast feeding and optimum feeding practices to improve breast feeding rates, says a recent report from the World Breastfeeding Trends Initiative (WBTi).1

In 2015 India scored 78/150 in the WBTi’s assessment of 15 factors in “policy and programmes” and “infant and young child feeding”—only a small improvement from 68/150 in 2005. India ranks poorly alongside other South Asian countries such as Bangladesh, Sri Lanka, and even Afghanistan, which made significant progress in its assessment from 30/150 …
Anemia and Congestive Heart Failure
Authors: Katharina Schroecksnadel, Barbara Wirleitner, Dietmar Fuchs
Journal: Circulation (2003)

Anemia and Congestive Heart FailureTo the Editor:With great interest we read the article by Ezekowitz et al 1 focusing on the high prevalence and possible causes of anemia in patients with congestive heart failure.Most patients in their cohort had anemia of chronic disease.In patients with cardiomyopathy, anemia obviously coincides with immune activation, given that raised concentrations of immune activation markers such as neopterin were found in patients, correlating with left ventricular functional tests and New York Heart Association classes. 2 Neopterin is formed by human macrophages on stimulation with interferon-␥ (IFN-␥) in scope with Th1-type immune response.IFN-␥, especially in cooperation with tumor necrosis factor ␣, is well known to suppress the growth of erythroid precursor cells and appears to be deeply involved in the pathogenesis of anemia of chronic diseases. 3The suppressive effect of IFN-␥ on hematopoiesis is so far mainly attributed to direct cytokine interaction with bone marrow stem cells; still, the exact mechanisms underlying this process remain unclear.A possible explanation for hematopoietic suppression could be an accelerated tryptophan degradation, because IFN-␥ induces enzyme indolamine-2,3-dioxygenase, which converts the essential amino acid tryptophan to kynurenine.Tryptophan is essential for cellular growth.Thus, tryptophan depletion is capable of inhibiting cell proliferation and may contribute to development of T-cell unresponsiveness. 4Earlier enhanced tryptophan degradation was shown in patients with congestive heart failure 2 and in patients suffering from other chronic diseases.Recently, decreased hematopoiesis was found in the bone marrow of mice with heart failure. 5Thus, enhanced degradation of tryptophan could also be the rate-limiting step in hematopoiesis.Consequently, in several diseases with chronic immune activation and concomitant release of IFN-␥, an increased activity of indoleamine-2,3-dioxygenase could be involved in the drop of hemoglobin and the development of anemia.
A Prospective Phase II Study of Cisplatin and Cremophor EL-Free Paclitaxel (Genexol-PM) in Patients with Unresectable Thymic Epithelial Tumors
Authors: Hae Su Kim, Ji Yun Lee, Sung Hee Lim, Jong-Mu Sun, Se Hoon Lee, Jin Seok Ahn, Keunchil Park, Seung Hwan Moon, Myung-Ju Ahn
Journal: Journal of Thoracic Oncology (2015)
Recurrent Panniculitis as the First Clinical Manifestation of Recurrent Acute Pancreatitis Secondary to Cholelithiasis
Authors: K S Cheng, G Stansby, N Law, R Gardham
Journal: Journal of the Royal Society of Medicine (1996)

A case of recurrent panniculitis in the legs as the first clinical manifestation of recurrent acute pancreatitis secondary to cholelithiasis is described in a 59-year-old Caucasian woman.
Spectral Tuning of Killer Whale (<i>Orcinus orca</i>) Rhodopsin: Evidence for Positive Selection and Functional Adaptation in a Cetacean Visual Pigment
Authors: Sarah Z. Dungan, Alexander Kosyakov, Belinda S.W. Chang
Journal: Molecular Biology and Evolution (2015)

Cetaceans have undergone a remarkable evolutionary transition that was accompanied by many sensory adaptations, including modification of the visual system for underwater environments. Recent sequencing of cetacean genomes has made it possible to begin exploring the molecular basis of these adaptations. In this study we use in vitro expression methods to experimentally characterize the first step of the visual transduction cascade, the light activation of rhodopsin, for the killer whale. To investigate the spectral effects of amino acid substitutions thought to correspond with absorbance shifts relative to terrestrial mammals, we used the orca gene as a background for the first site-directed mutagenesis experiments in a cetacean rhodopsin. The S292A mutation had the largest effect, and was responsible for the majority of the spectral difference between killer whale and bovine (terrestrial) rhodopsin. Using codon-based likelihood models, we also found significant evidence for positive selection in cetacean rhodopsin sequences, including on spectral tuning sites we experimentally mutated. We then investigated patterns of ecological divergence that may be correlated with rhodopsin functional variation by using a series of clade models that partitioned the data set according to phylogeny, habitat, and foraging depth zone. Only the model partitioning according to depth was significant. This suggests that foraging dives might be a selective regime influencing cetacean rhodopsin divergence, and our experimental results indicate that spectral tuning may be playing an adaptive role in this process. Our study demonstrates that combining computational and experimental methods is crucial for gaining insight into the selection pressures underlying molecular evolution.
Lag period for diagnosing and starting treatment for pulmonary tuberculosis patients
Authors: Dushantha Madegedara, Damith Nandadeva, Samudani Dhanasekera, Hansa Kumara
Journal: European Respiratory Journal (2014)

Objective   To calculate the total lag period in diagnosing PTB patients.   Design   Descriptive cross sectional study   Methods   Information was collected from TB registry during December 2012 to M ay 2013 . Patients with two or more typical symptoms of PTB more than two weeks was taken as inclusion criterion [2] . Results were analyzed using Microsoft Excel 2010 software.   Results   63 patients were enrolled. 34 sputum positive patients age range of 9-70 years (41.76±17.43) were found; out of them, 25 were males. Among those 24(70.58%) had cough, 9(29.47%) haemoptysis, 14(41.17%) fever, 20(58.87%) LOA and 13(38.23%) with LOW. The mean lag period for positive PTB was 7.05±6.16 weeks.  29 PTB negative patients with the age range of 13-69 years (57.34±18.98) were included. Out of them 14 were male patients. They presented with cough 21(72.41%), haemoptysis 3 (10.34%), fever 8(27.58%), LOA 14 (48.27%) and LOW 11(37.93%). The mean lag period for sputum negative PTB group was 7.93±6.93 weeks.  20 positive (58.82%) and 19 negative (65.51%) PTB patients had a delayed diagnosis while taking treatment from a health care professional.   Conclusion   Both group of patients had significant delayed diagnosis. Out of these two groups, delay in diagnosis of smear positive patients has adverse impact on the general population as during this period a patient can infect the community. This in turn affects the prevalence of TB locally and globally.  Although health care personals were educated during their course of training and continued medical education, significant delay in diagnosis occurred at their level.  Continuous awareness and high degree of suspicion of TB is essential among the health care personals and general public.
ACUTE HEPATITIS ASSOCIATED WITH MOUSE LEUKEMIA
Authors: John B. Nelson
Journal: The Journal of Experimental Medicine (1952)

On four occasions a naturally occurring mouse leukemia, which was maintained by serial passage in weanlings of the Princeton strain, was superseded by a syndrome typical of acute hepatitis. Once initiated, the disease was regularly transmissible by the injection of liver suspensions of sick mice. It was also passed, though irregularly, by feeding such suspensions, and it also followed cannibalism. The course of the disease after intraperitoneal injection of liver suspensions into normal weanlings was commonly less than 7 days and the mortality rate nearly 100 per cent. Focal or diffuse necrosis of the liver was the only constant lesion at autopsy. On recovery, which occurred only in exceptional cases, cirrhosis was often found. The primary source of the disease was undetermined. Latent carriage by healthy mice was not detectable on direct examination nor by the serial passage of suspensions of normal livers.