tbuckley/cabot-search huggingface dataset:
Nasal CPAP or Intubation at Birth for Very Preterm Infants
Authors: Colin J. Morley, Peter G. Davis, Lex W. Doyle, Luc P. Brion, Jean-Michel Hascoet, John B. Carlin
Journal: New England Journal of Medicine (2008)

Bronchopulmonary dysplasia is associated with ventilation and oxygen treatment. This randomized trial investigated whether nasal continuous positive airway pressure (CPAP), rather than intubation and ventilation, shortly after birth would reduce the rate of death or bronchopulmonary dysplasia in very preterm infants.We randomly assigned 610 infants who were born at 25-to-28-weeks' gestation to CPAP or intubation and ventilation at 5 minutes after birth. We assessed outcomes at 28 days of age, at 36 weeks' gestational age, and before discharge.At 36 weeks' gestational age, 33.9% of 307 infants who were assigned to receive CPAP had died or had bronchopulmonary dysplasia, as compared with 38.9% of 303 infants who were assigned to receive intubation (odds ratio favoring CPAP, 0.80; 95% confidence interval [CI], 0.58 to 1.12; P=0.19). At 28 days, there was a lower risk of death or need for oxygen therapy in the CPAP group than in the intubation group (odds ratio, 0.63; 95% CI, 0.46 to 0.88; P=0.006). There was little difference in overall mortality. In the CPAP group, 46% of infants were intubated during the first 5 days, and the use of surfactant was halved. The incidence of pneumothorax was 9% in the CPAP group, as compared with 3% in the intubation group (P<0.001). There were no other serious adverse events. The CPAP group had fewer days of ventilation.In infants born at 25-to-28-weeks' gestation, early nasal CPAP did not significantly reduce the rate of death or bronchopulmonary dysplasia, as compared with intubation. Even though the CPAP group had more incidences of pneumothorax, fewer infants received oxygen at 28 days, and they had fewer days of ventilation. (Australian New Zealand Clinical Trials Registry number, 12606000258550.).
Effect of the Genetic Background on the Phenotype of Mouse Mutations
Authors: XAVIER MONTAGUTELLI
Journal: Journal of the American Society of Nephrology (2000)

Abstract. An increasing number of scientific articles report that the phenotype of a given single gene mutation in mice is modulated by the genetic background of the inbred strain in which the mutation is maintained. This effect is attributable to so-called modifier genes, which act in combination with the causative gene. The modulation of the phenotype can be major, as exemplified in the case of several mouse models of polycystic kidney disease. Because of the existence of inbred strains and the possibility of developing congenic strains, the effect of the genetic background can be analyzed in mice, including the identification of major modifier genes. Furthermore, by transferring a given mutation into different genetic backgrounds, mouse models can be manipulated with the aim of more accurately mimicking specific features of human diseases.
Pioglitazone Treatment Improves Nitrosative Stress in Type 2 Diabetes
Authors: Aaron I. Vinik, Jagdeesh Ullal, Henri K. Parson, Patricia M. Barlow, Carolina M. Casellini
Journal: Diabetes Care (2006)

OBJECTIVE—The purpose of this study was to determine the effect of 24 weeks of treatment with 45 mg/day pioglitazone on peripheral skin blood flow (SkBF) and skin nitric oxide (NO) production in vivo in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—This was a randomized, parallel, cross-over, double-blind, within- and between-subject study designed to compare vascular responses before and after treatment. We studied 12 subjects with type 2 diabetes (average age 58.6 ± 30.8 years, HbA1c 7.9 ± 00.4%, BMI 31.3 ± 1.2 kg/m2). SkBF was measured using laser Doppler techniques in response to ischemia reperfusion and local skin warming, and NO production was assessed in vivo using an amperometric NO meter inserted directly into the skin. These measurements were performed before treatment and at 6 and 24 weeks. RESULTS—The SkBF response was not significantly improved after 24 weeks in either of the groups. NO production was significantly decreased in the pioglitazone-treated group in the basal condition (area under the curve 6.4 ± 1.0 vs. 2.8 ± 0.8, P &amp;lt; 0.01), after local heat stimulation at 40°C (12.9 ± 2.2 vs. 5.7 ± 1.7, P &amp;lt; 0.01), and after nociceptor stimulated flow with local heating at 44°C (36.4 ± 6.3 vs. 16.6 ± 3.4). Differences were not significant in the placebo-treated group. CONCLUSIONS—Treatment of patients with type 2 diabetes with pioglitazone for 24 weeks reduced skin NO production, thus probably reducing nitrosative stress without a demonstrable effect on SkBF. Because nitrosative stress is considered to be a factor in the pathogenesis of neurovascular dysfunction, these findings warrant further investigation.
Bone marrow–derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation
Authors: Jens M Nygren, Stefan Jovinge, Martin Breitbach, Petter Säwén, Wilhelm Röll, Jürgen Hescheler, Jalal Taneera, Bernd K Fleischmann, Sten Eirik W Jacobsen
Journal: Nature Medicine (2004)
Induction of lymphokine-activated killer-like cells by cancer chemotherapy.
Authors: T Kiyohara, K Taniguchi, S Kubota, S Koga, T Sakuragi, Y Saitoh
Journal: The Journal of Experimental Medicine (1988)

Natural cell-mediated cytotoxicity against NK-resistant target tumor cells was found in the peripheral blood of tumor-bearing patients approximately 1 mo after combined chemotherapy. The recognition specificity of these effector cells was broad and had no restriction. From the experiments of negative selection with mAbs and complements, these newly developed killer cells after chemotherapy were thought to be LAK-like cells. Contribution of these LAK-like cells to the mechanism of action of anticancer drugs remains to be clarified.
A Drug Repositioning Approach Identifies Tricyclic Antidepressants as Inhibitors of Small Cell Lung Cancer and Other Neuroendocrine Tumors
Authors: Nadine S. Jahchan, Joel T. Dudley, Pawel K. Mazur, Natasha Flores, Dian Yang, Alec Palmerton, Anne-Flore Zmoos, Dedeepya Vaka, Kim Q.T. Tran, Margaret Zhou, Karolina Krasinska, Jonathan W. Riess, Joel W. Neal, Purvesh Khatri, Kwon S. Park, Atul J. Butte, Julien Sage
Journal: Cancer Discovery (2013)

Small cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with high mortality. We used a systematic drug repositioning bioinformatics approach querying a large compendium of gene expression profiles to identify candidate U.S. Food and Drug Administration (FDA)-approved drugs to treat SCLC. We found that tricyclic antidepressants and related molecules potently induce apoptosis in both chemonaïve and chemoresistant SCLC cells in culture, in mouse and human SCLC tumors transplanted into immunocompromised mice, and in endogenous tumors from a mouse model for human SCLC. The candidate drugs activate stress pathways and induce cell death in SCLC cells, at least in part by disrupting autocrine survival signals involving neurotransmitters and their G protein-coupled receptors. The candidate drugs inhibit the growth of other neuroendocrine tumors, including pancreatic neuroendocrine tumors and Merkel cell carcinoma. These experiments identify novel targeted strategies that can be rapidly evaluated in patients with neuroendocrine tumors through the repurposing of approved drugs.Our work shows the power of bioinformatics-based drug approaches to rapidly repurpose FDA-approved drugs and identifies a novel class of molecules to treat patients with SCLC, a cancer for which no effective novel systemic treatments have been identified in several decades. In addition, our experiments highlight the importance of novel autocrine mechanisms in promoting the growth of neuroendocrine tumor cells.
Diagnostic role of fiberoptic bronchoscopy in suspected smear negative pulmonary tuberculosis
Authors: Mahler Beatrice, Ramona Nedelcu, Ruxandra Ulmeanu, Gina Ciolan, Mihaela Tanasescu, Mara Popescu, Constantin Marica
Journal: European Respiratory Journal (2012)

Background: Sputum smear-negative pulmonary tuberculosis is a common problem faced by clinicians. Bronchoscopy-related transmission of Mycobacterium tuberculosis is rarely reported.

Methods: The retrospectively study evaluated 40 patients(26males, 14females; mean age 45±19.6years; range:19-88years) who had respiratory symptoms and radiographic findings consistent with pulmonary TB, but who were unable to produce sputum spontaneously or had three samples of spontaneously produced sputum that was smear-negative for AFB. Induced sputum tests, bronchial washings and bronchoalveolar lavage were performed where indicated. The relevant specimens were sent for direct smear for acid fast bacilli by Ziel-Neelsen method and culture for M. tuberculosis in Lowenstein medium. Data obtained were analyzed using MS Excel 2007.

Results: Bronchoscopy confirmed or contributed to the diagnosis in 18 patients. In 8 patients(45.5%) upper lobe mucosal inflammation with/without narrowing and scarring was detected. Sputum culture confirmed the diagnosis in 12(30%) cases: 7(17.5%) had culture positive specimens(p<0.005), 4(10%) was culture positive on bronchoscopy and one(2.5%) on induced sputum. All patients had negative HIV test, 31(77.5%) new cases and 35(87.5%) with high erythrocyte sedimentation rate. Majority of radiological findings were infiltrative ulcerated and cavitation lesions which affect one lobe lung.

Conclusions: Flexible bronchoscopy is a widely accepted diagnostic modality for tuberculosis specifically in patients who cannot produce an adequate sputum sample despite hypertonic saline induction. Bronchial aspirates obtained during bronchoscopy considerably increase the diagnostic yield in tuberculosis.
Does Psychotherapy Affect the Survival of Cancer Patients? More Questions Than Answers
Authors: Fernando Dimeo, Eckhard Thiel
Journal: Journal of Clinical Oncology (2007)

off-label use.As stated in our methods, patients receiving trastuzumab off-label were registered in the program as receiving monotherapy, but had at least two dispensing records for taxane or nontaxane chemotherapy, or were registered as receiving trastuzumab with taxanes and had at least two dispensing records for second-line nontaxane therapy.As such, enrollees commencing trastuzumab therapy with taxanes and a platinum compound were not included in our off-label estimates.Furthermore, we did not present the full extent of off-label use as we did not include the use of trastuzumab with single-agent cyclophosphamide, fluorouracil, gemcitabine, capecitabine, and vincristine in our estimates.If these drugs were included, the off-label use increases to 25%.Finally, the authors question one of our interpretations of the finding that there was a longer median duration of therapy in the real-world clinical practice compared with the original trial evidence.The authors cite two recent trials 12,13 with outcomes more closely approximating our real-world estimates.Interestingly, patients in these trials had more stringent inclusion criteria (restricting entry to women with immunohistochemical staining 3ϩ and/or fluorescent in situ hybridization-positive disease) than those in the original Slamon et al study (2ϩ or 3ϩ on IHC), 14 and these more stringent criteria mirror exactly, the requirement for enrollment on the Herceptin Program.As per our comments in the published article, "the longer duration of therapy in clinical practice may reflect a greater benefit of trastuzumab, perhaps because of better HER-2 target identification." 1 Based on the evidence from the two recent trials, it is possible that the variation between our study findings and those of the Slamon et al trial can be attributed to better target identification.However, we cannot totally discount the hypothesis that the longer duration reflects "reluctance on the part of physicians and patients to cease a drug viewed as doing no harm." 1 Furthermore, Drs Chan and de Boer have either discounted or failed to acknowledge our primary point around this issue, which is that the duration and cost of therapy impacts its costeffectiveness.While off-label trastuzumab use may offer a clinical benefit, this does not imply this treatment strategy is cost-effective and hence affordable.Monitoring the use of drugs in the real-world setting is crucial, but accurate conclusions can only be drawn by using unbiased data sets.Drs Chan and de Boer base their arguments on the unfounded belief that all doctors practice as they do, and that their data on "at least 50 women" are superior to data collected from nearly 1,500 individuals.
A RECENT SERIES OF 60 CASES OF TOTAL ENUCLEATION OF THE PROSTATE FOR RADICAL CURE OF ENLARGEMENT OF THAT ORGAN
Authors: P. J. Freyer
Journal: BMJ (1905)

The,heart beat could i,ot be distinctly felt on that account, ;and the pulse was extremely irregular and intermittent.The patient looked in fairly good health, although he was *'asthmatic," and had suffered a great deal from the frequent passage of catheter by day and night during the previous 'three months.I removed the prostate in October, 1904.Dr. Cyril Lewis gave the anaesthetic, Dr. Jones assisted, and Mr. Cresswell, (.B., was present.The prostate and its eapsule were the toughest I have had to deal with and were removed piecemeal-four adenomata and three tough frag- *ments of capsule.My left forefinger got tired out, and I had -to usemy right forefinger before the operation was completed.Rubber gloves were used on the hands when manipulating in the rectum.On the night of the operation I was afraid he was in for an attack of bronchitis, but an emetic removed all anxiety.From the eighteenth day after operation he passed urine entirely per uretbram, and went home on the twenty- sixth day, retaining and passing his urine quite normally.lln March, I905, he reported himself, and said the result was perfect-" I do not get up at night."]In conclusion, I would venture to remark about the use of antiseptics in these operations.Weak antiseptic solutions for washing out the bladder are only a source of local irrita- tion, plus the possibility of being absorbed and throwing unnecessary tax upon the eliminating organs.Sterilized salt solution is better for irrigation, because the beneficial effect is really due to the mechanical removal of surgical dirt.Antiseptics to be of any germicidal value must be strong, and for suprapubic operations upon the bladder I find that pure tincture of iodine poured into the bladder (2 to 4 dr.) through the suprapubic opening is an excellent preparation to correct peptic conditions either at the time of operation or at subse- quent dressings.It is better than any powder, because it 'runs into all the nooks and crevices, and comes into con- tact with the entire field of operation.[Since the above paper was written Messrs.Weiss and Son tave made for me a special elevator for lifting up the base of ,the bladder, and in two suprapubic operations I found it most -useful; in one case where my fingers were too short without it I was able to pick out 47 calculi from a post-prostatic pouch -before I removed a big prostate.The elevator is passed into the rectum, and is under control of the operator.I hope later on to relate cases in which such an instrument is of great -value in raising the pelvic floor through rectum or vagina, in dovariotomy, hysterectomy, and bladder operations.]
Exercise to reduce 'potbelly'
Authors: J. A. Spataro, L. Van Horn
Journal: JAMA (1995)

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MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologue
Authors: Sashwati Roy, Savita Khanna, Syed-Rehan A. Hussain, Sabyasachi Biswas, Ali Azad, Cameron Rink, Surya Gnyawali, Shani Shilo, Gerard J. Nuovo, Chandan K. Sen
Journal: Cardiovascular Research (2009)

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level by either degradation or translational repression of a target mRNA. Encoded in the genome of most eukaryotes, miRNAs have been proposed to regulate specifically up to 90% of human genes through a process known as miRNA-guided RNA silencing. For the first time, we sought to test how myocardial ischaemia-reperfusion (IR) changes miR expression.Following 2 and 7 h of IR or sham operation, myocardial tissue was collected and subjected to miRNA expression profiling and quantification using a Bioarray system that screens for human-, mice-, rat-, and Ambi-miR. Data mining and differential analyses resulted in 13 miRs that were up-regulated on day 2, 9 miRs that were up-regulated on day 7, and 6 miRs that were down-regulated on day 7 post-IR. Results randomly selected from expression profiling were validated using real-time PCR. Tissue elements laser-captured from the infarct site showed marked induction of miR-21. In situ hybridization studies using locked nucleic acid miR-21-specific probe identified that IR-inducible miR-21 was specifically localized in the infarct region of the IR heart. Immunohistochemistry data show that cardiac fibroblasts (CFs) are the major cell type in the infarct zone. Studies with isolated CFs demonstrated that phosphatase and tensin homologue (PTEN) is a direct target of miR-21. Modulation of miR-21 regulated expression of matrix metalloprotease-2 (MMP-2) via a PTEN pathway. Finally, we noted a marked decrease in PTEN expression in the infarct zone. This decrease was associated with increased MMP-2 expression in the infarct area.This work constitutes the first report describing changes in miR expression in response to IR in the mouse heart, showing that miR-21 regulates MMP-2 expression in CFs of the infarct zone via a PTEN pathway.
Nitric Oxide Diffusing Capacity and Alveolar Microvascular Recruitment in Sarcoidosis
Authors: Anagha R. Phansalkar, Chad M. Hanson, Ahmed R. Shakir, Robert L. Johnson, Connie C. W. Hsia
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

We measured diffusing capacities for carbon monoxide (DLCO) and nitric oxide, lung volume, and cardiac output by a rebreathing technique at two alveolar O2 tensions (PAO2) at rest and exercise. Membrane diffusing capacity for CO (DMCO) and VC were estimated from DLCO by the Roughton-Forster (RF) method and also from simultaneous lung diffusing capacity for NO and DLCO measured at one O2 tension (modified RF method). Estimates by these methods agreed closely in normal subjects (Tamhane et al., Chest 2001;120:1850-1856). Using these methods, we studied patients with stages II-III pulmonary sarcoidosis to determine (1) whether the modified RF method accurately estimates DMCO and VC in parenchymal disease and (2) whether sarcoidosis alters recruitment of diffusing capacity with respect to cardiac output. In patients, DMCO and VC estimated by the two methods agreed closely. DMCO was disproportionately reduced relative to VC at any given cardiac output, and the slope of the relationship between DLCO and cardiac output was moderately, though significantly, below normal. We conclude that in sarcoidosis (1) the modified RF method provides comparable estimates of DMCO and VC as the standard RF method and (2) the limitation to diffusive gas transport resides primarily in the membrane barrier, although recruitment of microvascular reserves is also modestly impaired.
Real budgets for GPs will present "significant challenges," experts predict
Authors: A. O'Dowd
Journal: BMJ (2010)

The policy of giving GPs real budgets to commission health services could improve the care of patients and save money but will be difficult to implement, health experts say.

A joint report published on 23 June by six leading NHS organisations and think tanks says that several major challenges lie ahead if commissioning by GPs is to take off and succeed.

The report says that the new coalition government had made clear its intention to give GPs power and responsibility for holding real budgets and to commission health services on behalf of patients.

The organisations—the Nuffield Trust, National Association of Primary Care, NHS Alliance, NHS Confederation’s PCT …
Prevention of fat-induced insulin resistance by salicylate
Authors: Jason K. Kim, Yoon-Jung Kim, Jonathan J. Fillmore, Yan Chen, Irene Moore, Jongsoon Lee, Minsheng Yuan, Zhi Wei Li, Michael Karin, Pascale Perret, Steven E. Shoelson, Gerald I. Shulman
Journal: Journal of Clinical Investigation (2001)

Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and may involve fat-induced activation of a serine kinase cascade involving IKK-β. To test this hypothesis, we first examined insulin action and signaling in awake rats during hyperinsulinemic-euglycemic clamps after a lipid infusion with or without pretreatment with salicylate, a known inhibitor of IKK-β. Whole-body glucose uptake and metabolism were estimated using [3-3H]glucose infusion, and glucose uptake in individual tissues was estimated using [1-14C]2-deoxyglucose injection during the clamp. Here we show that lipid infusion decreased insulin-stimulated glucose uptake and activation of IRS-1–associated PI 3-kinase in skeletal muscle but that salicylate pretreatment prevented these lipid-induced effects. To examine the mechanism of salicylate action, we studied the effects of lipid infusion on insulin action and signaling during the clamp in awake mice lacking IKK-β. Unlike the response in wild-type mice, IKK-β knockout mice did not exhibit altered skeletal muscle insulin signaling and action following lipid infusion. In summary, high-dose salicylate and inactivation of IKK-β prevent fat-induced insulin resistance in skeletal muscle by blocking fat-induced defects in insulin signaling and action and represent a potentially novel class of therapeutic agents for type 2 diabetes.
On the concept of animal innovation and the challenge of studying innovation in the wild
Authors: Grant Ramsey, Meredith L. Bastian, Carel van Schaik
Journal: Behavioral and Brain Sciences (2007)

Abstract The commentaries have both drawn out the implications of, and challenged, our definition and operationalization of innovation. In this response, we reply to these concerns, discuss the differences between our operationalization and the preexisting operationalization if innovation, and make suggestions for the advancement of the challenging and exciting field of animal innovation.