tbuckley/cabot-search huggingface dataset:
Concomitant Infusional Paclitaxel and Fluorouracil, Oral Hydroxyurea, and Hyperfractionated Radiation for Locally Advanced Squamous Head and Neck Cancer
Authors: Merrill S. Kies, Daniel J. Haraf, Fred Rosen, Kerstin Stenson, Marcy List, Bruce Brockstein, Theodore Chung, Bharat B. Mittal, Harold Pelzer, Louis Portugal, Alfred Rademaker, Ralph Weichselbaum, Everett E. Vokes
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To improve local disease control and survival with organ preservation, we conducted a phase II multi-institutional trial with a concomitant taxane-based chemotherapy and hyperfractionated radiation regimen. PATIENTS AND METHODS: Sixty-four patients with locally advanced squamous cancers (stage IV, 98%; N2/3, 81%) were treated on an intensive regimen consisting of 5-day (120-hour) infusions of paclitaxel (20 mg/m 2 /d) and fluorouracil (600 mg/m 2 /d), oral hydroxyurea 500 mg every 12 hours for 11 doses, and radiation 1.5 Gy bid (T-FH2X). Chemoradiation was administered concomitantly on days 1 to 5 of each 14-day cycle. A full treatment course consisted of five cycles during a 10-week period to a total radiation dose of 72 to 75 Gy. RESULTS: The median follow-up for the group is 34 months. At 3 years, progression-free survival is 63%, locoregional control is 86%, and systemic control is 79%; overall survival is 60%. Seventeen patients died of recurrent cancer, two died of second primary cancers, and four died of other causes. Side effects observed include anemia (22% required transfusion), leucopenia (34%, grade 3 to 4), and mucositis (84%, grade 3 to 4). Organ preservation principles were maintained. At 1 year posttreatment, 61% of patients had severe xerostomia and 47% had compromised swallowing. There was little disturbance of speech quality in 97% of patients at the same follow-up point. CONCLUSION: T-FH2X is a highly active and tolerable concomitant chemotherapy and hyperfractionated radiation regimen that induces sustained local tumor control and holds promise for improved survival with organ preservation in high-risk patients. Identification of less toxic therapy and improved distant disease control are needed. T-FH2X should be tested in a randomized trial and compared with a less intensive concomitant regimen that uses once-daily radiation fractionation.
Overexpression of RAGE in lungs of patients with COPD: A contributor to oxidative stress in COPD
Authors: Lei Chen, Lin Liu, Tao Wang, Fuqiang Wen
Journal: European Respiratory Journal (2011)

Background:  Receptor for advanced glycation end products (RAGE) has been recently suggested to be implicated in COPD, although the mechanisms remain unclear. The aim of this study is to investigate the expression of RAGE in lung tissues from COPD patients and its potential role in oxidative stress in COPD.   Methods:  Peripheral lung tissue specimens were obtained from 40 patients who underwent lung resection for non-small cell lung cancer, including 8 non-smoker controls, 7 non-COPD smokers and 25 smoker COPD patients. Immunohistochemistry and ELISA were used to assess RAGE expression in lung tissues, and oxidative stress was also measured by ROS and GSH. Furthermore, human pulmonary epithelial cell (A549) and bronchial epithelial cell (16HBE) were cultured with cigarette smoke extract (CSE). Neutralizing antibody against RAGE was used to detect the role of RAGE in oxidative stress in COPD.   Results:  RAGE expression level in smoker COPD patients was significantly higher than non-smoker controls and non-COPD smokers, which was dominantly expressed in the bronchiolar and alveolar epithelia. Importantly, RAGE in smoker COPD patients was positively correlated with oxidative stress, evidenced by levels of ROS and GSH. In the in-vitro study, CSE enhanced oxidative stress level in A549 and 16HBE cells, as well as activation of NF-kB, a key redox transcription factor, which were all reversed by pretreatment of anti-RAGE antibody.   Conclusion:  Overexpression of RAGE may contribute to COPD pathogenesis, at least partly through enhancement of oxidative stress level.
Design of clone-specific probes from genome sequences for rapid PCR-typing of outbreak pathogens
Authors: E. López-Camacho, Z. Rentero, G. Ruiz-Carrascoso, J.-J. Wesselink, M. Pérez-Vázquez, S. Lusa-Bernal, P. Gómez-Puertas, R.A. Kingsley, P. Gómez-Sánchez, J. Campos, J. Oteo, J. Mingorance
Journal: Clinical Microbiology and Infection (2014)
Pre-emptive therapy with azoles in lung transplant patients
Authors: J. Hamacher, A. Spiliopoulos, A-M Kurt, L.P. Nicod, None and the Geneva Lung Transplantation Group
Journal: European Respiratory Journal (1999)

Pulmonary fungal infection is diagnosed in up to 15-25% of lung transplant recipients and frequently bears a fatal outcome. This prospective uncontrolled study addresses the efficacy and safety of pre-emptive azole therapy against fungal infection in these patients. Fluconazole or itraconazole have been systematically used according to reported fungus sensitivity after the discovery of fungi in lower respiratory tract samples. Patients were treated until the bronchial suture was normal and the cultures of the following bronchoscopy remained negative. Fungi were found post-transplantation in the lower respiratory tract specimens of 26 out of 31 (84%) patients, predominantly Candida albicans (20 patients) and Aspergillus fumigatus (16 patients). Mycelia characteristic of Candida spp. or Aspergillus spp. were found in necrotic tissue at the bronchial suture of nine patients. The mean duration of the 38 treatments was 3.6+/-2.6 months (range, 0.5-12 months). After a median follow-up of 16 (range, 0-48) months, two cases of extended ulcerative and pseudo membranous Aspergillus fumigatus bronchitis were observed and healed under itraconazole treatment. In conclusion, pre-emptive azole therapy may be effective and well-tolerated in lung transplant patients where fungi are found in the airways or pleura.
Tuberculosis (TB) in homeless population in Poland
Authors: Izabela Siemion-Szczesniak, Maria Korzeniewska-Kosela, Jan Kus
Journal: European Respiratory Journal (2014)

Background: Homelessness is recognized as risk factor associated with TB and non adherence to treatment.  Objective: Comparison of TB features in homeless and non homeless patients in Poland.  Methods: Data of 75921 cases with TB registered in the national Central TB Register from 2002 to 2013 were analyzed. Chi-squared test was used to assess statistical significance (SS).  Results: There were 2388 cases of TB in homeless. Mean age of homeless was 49.7 (±10.9 yrs), and non homeless 52.8 (±17.5) yrs, which was a SS difference (p  Conclusion: The results of the study indicate that homelessness is strongly associated with pulmonary and infectious TB, poor treatment outcomes including high default rate and high rate of relapse in TB in patients in Poland. Special attention should be put to the direct observation of treatment in these patients. Extrapulmonary TB predominates in non homeless.
VP-16 plus ifosfamide plus cisplatin as salvage therapy in refractory germ cell cancer.
Authors: P J Loehrer, L H Einhorn, S D Williams
Journal: Journal of Clinical Oncology (1986)

Forty-eight evaluable male patients with germ cell tumors (GCT) failing to be cured with first-line therapy were treated with VP-16 (75 mg/m2), ifosfamide (1.2 g/m2), and cisplatin (20 mg/m2) (VIP), all given daily for 5 consecutive days every 3 weeks. All patients either achieved an unresectable partial remission as their best response to induction chemotherapy (Group A), relapsed from complete remission (CR) less than or equal to 2 months after induction therapy (Group B), or had received cisplatin plus VP-16 as previous salvage therapy (Group C). Nine (19%) had extragonadal GCT, and 37 (77%) had advanced disease. Twenty-three (48%) of the patients had greater than or equal 2 prior treatment regimens. Sixteen of 48 (33%) achieved CR with VIP treatment alone or following surgical excision of residual disease. Six of 22 (27%), three of seven (43%), and seven of 19 (37%) patients from groups A, B, and C, respectively, attained a CR. The median survival time of all patients was 7 months (range 0 to 28+) with seven patients remaining continuously free of disease (four patients greater than 1 year). Myelosuppression was significant with a median WBC nadir of 900/mm2 and platelet nadir of 24,000/mm2. Fourteen (26%) had granulocytopenic fever, and renal insufficiency developed in 15%. VIP combination chemotherapy demonstrates activity in this highly unfavorable population of patients with germ cell tumors. The actual contribution of ifosfamide in this regimen is unclear, but these results compare favorably to our experience with similar patients treated with cisplatin plus VP-16 alone. Further studies with VIP as initial salvage therapy for patients with GCT are planned.
LSC 2013 abstract - Mast cells support rhinovirus but not respiratory syncytial virus replication and contribute to the pro-inflammatory response to rhinovirus
Authors: Emily J. Swindle, Cornelia Blume, Peter Collins, Dean D. Metcalfe, Stephen T. Holgate, Donna E. Davies
Journal: European Respiratory Journal (2013)

Rationale: Respiratory virus infections (Respiratory Syncytial Virus (RSV), Rhinovirus (RV)) are major causes of persistent wheeze in infants and predict the development of asthma in later life. Mast cell (MC) numbers and reticular basement membrane thickness are increased in children with recurrent wheeze at age 1yr and predicts respiratory morbidity at age 3yrs. This suggests an important interaction between viral infection and MCs leading to allergic inflammation and development of asthma in young children. Since MCs have a key role in innate immunity to pathogens we hypothesized that MCs contribute to the innate immune response to viral infection in asthma.

Methods: The human MC line, LAD2, was infected with RSV or RV16 for 1h. After washing, MCs were cultured for 24h. Viral infection was determined by detection of gfp-RSV by flow cytometry or RV viral RNA by real-time PCR and virion release by TCID50 assay. Anti-viral and pro-inflammatory responses were assessed by real-time PCR. Degranulation was assessed by β-hex release.

Results: Exposure of MCs to RV16 but not RSV resulted in detectable viral RNA and increased IFNβ expression indicating that MCs support RV replication and mount an antiviral response. Virions were also released by MCs exposed to RV demonstrating that MCs release infective virus particles. RSV and RV16 did not induce MC degranulation. Investigations of mediator release by MCs showed increased IP-10 but not IL-8 or RANTES gene expression in response to RV16.

Conclusion: MCs contribute to the pro-inflammatory response to RV16 and may act as a viral reservoir and contribute to the development of asthma in early life.
Muscle remodelling is blunted in hypoxemic COPD patients after pulmonary rehabilitation
Authors: Frédéric Costes, Harry Gosker, Léonard Feasson, Marco Kelders, Annemie Schols, Damien Freyssenet
Journal: European Respiratory Journal (2012)

Pulmonary rehabilitation in COPD patients aims at increasing exercise tolerance, partly through improving muscle function. The influence of chronic hypoxia on the training-induced muscle adaptations has not been specifically investigated.

We studied muscle adaptations and exercise capacity following 2 months of endurance and resistance exercises in 8 COPD patients with long term oxygen therapy (hypoxic group) and 15 without arterial oxygen desaturation (normoxic group). Biopsies of the vastus lateralis were analyzed before and after training for fiber size, citrate synthase activity, and markers of protein synthesis/degradation.

At baseline both groups did not differ in pulmonary function, fat free mass, or exercise capacity. Maximal workload and walking distance improved in both groups but to a greater extent in the hypoxic group (27.5 versus 10.5%, p= 0.06; 23.7% versus 6.9%, p= 0.01, respectively). Fiber cross sectional area and citrate synthase activity increased significantly in the normoxic group only (both p<0.05). Levels of phosphorylated AKT, p70S6K and GSK3b tended to increase with training in the normoxic group in favour of an upregulation of anabolism while decreased significantly in the hypoxic group (p=0.01). mRNA levels of anabolic genes (IGF1, MGF) and catabolic genes (MurF-1, Atrogin, Foxo-1 and -3, Myostatin) did not change with training in both groups.

We conclude that in COPD patients with chronic hypoxemia, pulmonary rehabilitation improved exercise capacity while the markers of muscle remodelling remained unchanged. It deserves to be studied whether changes in genes expression occurred earlier during rehabilitation in these patients.
A double-edged sword: CRISPR-Cas9 is emerging as a revolutionary technique for genome editing
Authors: Chun-xiao Li, Hai-li Qian
Journal: Military Medical Research (2015)

In May 2015, Professor Xiao Yang authored a review on the development of CRISPR-Cas9 techniques in the journal of Military Medical Research. This review provided a valuable overview of this major scientific advance. It has been four years since the first publication of the CRISPR-Cas9 breakthrough (Science. 2012; 337: 816-21). The use of this technique has expanded into various scientific areas and is being developed into a systematic technical platform that may contribute to many bioengineering fields involving DNA sequence editing.
Asthma control test (ACT) versus intermittent oscillation system (IOS) assessment for control of asthmatic children
Authors: Malak Shaheen, Emad Mohamed, Mona El Ganzory
Journal: European Respiratory Journal (2011)

Background:  In spite of the great development of international guidelines for the diagnosis and the treatment of asthma, there is continuing evidence of poor control of childhood asthma.  Aim of this work was to evaluate the  subjective asthma control test  (ACT) against the  subjective  impulse oscillation system (IOS) measures of the airways resistance in asthmatic children.   Subject and methods:  This study included 35 asthmatic children. All the study children were subjected to the following; full medical history, clinical examination and spirometric FEV1 measurements (to fulfill GINA  assessment  for asthma control).  Children9s assessment  by ACT (using an Arabic version) was done. Finally; Impulse Oscillation test (IOS) was done to compare the  objective results  with the  subjective results  of ACT.   Results:  Score 19 was the cut off value differentiating children9s asthma control (compared to the gold standard IOS cut off values). Moderate agreement between CACT/ACT test for asthma control and R5 results; kappa test = 0.54 (P 0.05. Nevertheless; there was highly significant negative correlations between total scores of CACT/ACT and values of IOS results; P   Conclusion:  This study confirms that asthma control test (ACT) is a valid and cost effective instrument for assessment of control in asthmatic children.
Allergens in veterinary medicine
Authors: R. S. Mueller, J. Janda, E. Jensen‐Jarolim, C. Rhyner, E. Marti
Journal: Allergy (2015)

Allergic diseases in animals are increasingly gaining importance in veterinary practice and as research models. For intradermal testing and allergen immunotherapy, a good knowledge of relevant allergens for the individual species is of great importance. Currently, the knowledge about relevant veterinary allergens is based on sensitization rates identified by intradermal testing or serum testing for allergen-specific IgE; crude extracts are the basis for most evaluations. Only a few studies provide evidence about the molecular structure of (particularly) dust mite, insect and mould allergens in dogs and horses, respectively. In those species, some major allergens differ from those in humans. This position paper summarizes the current knowledge about relevant allergens in dogs, cats and horses.
Effect of Intestinal Bacteria on Incidence of Liver Tumors in Gnotobiotic C3H/He Male Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: T Mizutani, T Mitsuoka
Journal: JNCI Journal of the National Cancer Institute (1979)

The effect of intestinal microflora on liver tumorigenesis was studied in gnotobiotic C3H/He male mice monoassociated, diassociated, or polyassociated with the following strains of intestinal bacteria: Escherichia coli, Streptococcus faecalis, Bifidobacterium adolescentis, Bifidobacterium infantis, Clostridium indolis, C. paraputrificum, C. perfringens, C. innocuum, C. nexile, C. ramosum, C. clostridiiforme, Bacteroides multiacidus, Bacteroides fragilis, Veillonella alcalescens, V. parvula, and Lactobacillus acidophilus. The incidence of liver tumors was higher in most of the gnotobiotes (67--100%) and conventionalized mice (82%) derived from the germfree mice than in the germfree mice (39%). The average incidence of tumor nodules in gnotobiotes associated with E. coli, S. faecalis, and C. paraputrificum was 2.9, which was significantly higher than that in the conventionalized animals (1.6). In contrast, the average incidence of tumor nodules in gnotobiotes associated with E. coli, S. faecalis, L. acidophilus, C. perfringens, and Bacteroides fragilis (0.9) was not significantly different from that in germfree animals (0.5). The present study demonstrated that the presence of certain intestinal bacteria is related to liver tumorigenesis in gnotobiotic C3H/He male mice.
Comparison of invitro antimicrobial susceptibility tests of patients admitted in a tertiary respiratory center intensive care unit with their clinical symptoms related to ventilator associated pneumonia (in vivo results)
Authors: Majid Malekmohammad, Mohammadreza Hashemian, Parisa Adimi Naghan, Helenaz Fazlalizadeh, Makan Sadr, Hamidreza Jamaati
Journal: European Respiratory Journal (2012)

Background: Ventilator associated pneumonia (VAP),is the most common nosocomial infection in ICU admitted patients.There is no study about comparison of clinical response to routine VAP treatment and susceptibility of microorganism to antibiotics in VAP suspected patients.

Methods: In this cross-sectional retrospective study, the files of 99 mechanically ventilated patients in a respiratory center ICU were assessed. Patients demographic data, underlying diseases, Clinical Pulmonary Infection Score (CPIS), in vitro (culture) results, antibiogram and antibiotic regimen were recorded.The change in CPIS was considered as positive in vivo. The result of culture of secretions (especially tracheal secretion) was considerd as in vitro result.

Results: From 99 patients, 59 (60%) were male with a mean age of 42 years.14 patients (14%) had positive in vivo result and 19 patients (19%) had positive in vitro result. 60% of patients had given VAP antibiotic regimen. Comparison between results are seen in. 56% of patients with both positive results of in vivo and in vitro had resistant antibiotic susceptibility test in antibiogram. Near to half of patient with both negative results of in vivo and in vitro had given antibiotic regimen for VAP.

View this table:

comparison of invivo versus invitro results in ICU patients





Conclusion: More attention to clinical condition of patients (CPIS) than laboratory results is necessary for beginning of VAP antibiotic treatment.
Transformative Impact of Proteomics on Cardiovascular Health and Disease
Authors: Merry L. Lindsey, Manuel Mayr, Aldrin V. Gomes, Christian Delles, D. Kent Arrell, Anne M. Murphy, Richard A. Lange, Catherine E. Costello, Yu-Fang Jin, Daniel T. Laskowitz, Flora Sam, Andre Terzic, Jennifer Van Eyk, Pothur R. Srinivas
Journal: Circulation (2015)

The year 2014 marked the 20th anniversary of the coining of the term proteomics . The purpose of this scientific statement is to summarize advances over this period that have catalyzed our capacity to address the experimental, translational, and clinical implications of proteomics as applied to cardiovascular health and disease and to evaluate the current status of the field. Key successes that have energized the field are delineated; opportunities for proteomics to drive basic science research, facilitate clinical translation, and establish diagnostic and therapeutic healthcare algorithms are discussed; and challenges that remain to be solved before proteomic technologies can be readily translated from scientific discoveries to meaningful advances in cardiovascular care are addressed. Proteomics is the result of disruptive technologies, namely, mass spectrometry and database searching, which drove protein analysis from 1 protein at a time to protein mixture analyses that enable large-scale analysis of proteins and facilitate paradigm shifts in biological concepts that address important clinical questions. Over the past 20 years, the field of proteomics has matured, yet it is still developing rapidly. The scope of this statement will extend beyond the reaches of a typical review article and offer guidance on the use of next-generation proteomics for future scientific discovery in the basic research laboratory and clinical settings.
Recognition and Management of Individuals With Hyperglycemia Because of a Heterozygous Glucokinase Mutation
Authors: Ali J. Chakera, Anna M. Steele, Anna L. Gloyn, Maggie H. Shepherd, Beverley Shields, Sian Ellard, Andrew T. Hattersley
Journal: Diabetes Care (2015)

Glucokinase–maturity-onset diabetes of the young (GCK-MODY), also known as MODY2, is caused by heterozygous inactivating mutations in the GCK gene. GCK gene mutations are present in ∼1 in 1,000 of the population, but most are not diagnosed. They are common causes of MODY (10–60%): persistent incidental childhood hyperglycemia (10–60%) and gestational diabetes mellitus (1–2%). GCK-MODY has a unique pathophysiology and clinical characteristics, so it is best considered as a discrete genetic subgroup. People with GCK-MODY have a defect in glucose sensing; hence, glucose homeostasis is maintained at a higher set point resulting in mild, asymptomatic fasting hyperglycemia (5.4–8.3 mmol/L, HbA1c range 5.8–7.6% [40–60 mmol/mol]), which is present from birth and shows slight deterioration with age. Even after 50 years of mild hyperglycemia, people with GCK-MODY do not develop significant microvascular complications, and the prevalence of macrovascular complications is probably similar to that in the general population. Treatment is not recommended outside pregnancy because glucose-lowering therapy is ineffective in people with GCK-MODY and there is a lack of long-term complications. In pregnancy, fetal growth is primarily determined by whether the fetus inherits the GCK gene mutation from their mother. Insulin treatment of the mother is only appropriate when increased fetal abdominal growth on scanning suggests the fetus is unaffected. The impact on outcome of maternal insulin treatment is limited owing to the difficulty in altering maternal glycemia in these patients. Making the diagnosis of GCK-MODY through genetic testing is essential to avoid unnecessary treatment and investigations, especially when patients are misdiagnosed with type 1 or type 2 diabetes.