tbuckley/cabot-search huggingface dataset:
Animal Models of Neuropsychiatric Disorders
Authors: A.B.P. Fernando, T.W. Robbins
Journal: Annual Review of Clinical Psychology (2011)

We survey the utility of animal models of mental illness, based on the identification of possible neurocognitive or neurobehavioral endophenotypes. Three broad clusters of neuropsychiatric disorder are discussed: (a) impulsive-compulsive syndromes, comprising drug addiction, attention deficit/hyperactivity disorder, gambling, obsessive-compulsive disorder, and compulsive eating; (b) disorders at the cognitive-emotional interface, comprising anxiety, depression, and schizophrenia; and (c) disorders purely of cognition, which contribute to the third cluster, cognitive disorders. The emphasis is thus on modeling symptoms rather than disorders per se. We also distinguish between two main aspects of any validated model: the precise neurobehavioral or neurocognitive processes implicated from detailed study of the clinical phenotype, and the perturbations, whether typically genetic, environmental, pharmacological, or neurodevelopmental, that are designed to simulate relevant neural, neurochemical, or molecular aspects of particular neuropsychiatric disorders.
Bronchoalveolar lavage in extrinsic allergic alveolitis: effect of time elapsed since antigen exposure
Authors: M Drent, H van Velzen-Blad, M Diamant, SS Wagenaar, HC Hoogsteden, JM van den Bosch
Journal: European Respiratory Journal (1993)

The aim of the present study was to investigate whether bronchoalveolar lavage (BAL) cell profile and immunoglobulin levels from patients with extrinsic allergic alveolitis (EAA) were related to the time elapsed between last antigen exposure and BAL. For this purpose, an analysis was performed of BAL fluid (BALF) obtained from 59 nonsmoking EAA patients at various time-points after termination of antigen exposure and BAL. BALF early after antigen provocation (group 1: < 24 h) contained high absolute and relative numbers of lymphocytes, neutrophils, eosinophils and mast cells, and a low relative number of alveolar macrophages. When obtained after recent antigen exposure (group 2: 2-7 days), BALF showed high numbers of lymphocytes, plasma cells and mast cells, and high levels of immunoglobulins M, G and A (IgM, IgG and IgA). In BAL obtained one week or more after the final antigen exposure, (Group 3: 8-30 days; Group 4: 1-12 months) the distribution of all constituents showed a tendency to return to normal values, with the exception of the lymphocytes. These results demonstrate that BAL cell profile and immunoglobulin levels in EAA are highly dependent on the time-point at which the material is obtained in relation to the last exposure to the causative antigen.
Residual β-Cell Function 3–6 Years After Onset of Type 1 Diabetes Reduces Risk of Severe Hypoglycemia in Children and Adolescents
Authors: Jesper S. Sørensen, Jesper Johannesen, Flemming Pociot, Kurt Kristensen, Jane Thomsen, N. Thomas Hertel, Per Kjaersgaard, Caroline Brorsson, Niels H. Birkebaek
Journal: Diabetes Care (2013)

To determine the prevalence of residual β-cell function (RBF) in children after 3-6 years of type 1 diabetes, and to examine the association between RBF and incidence of severe hypoglycemia, glycemic control, and insulin requirements.A total of 342 children (173 boys) 4.8-18.9 years of age with type 1 diabetes for 3-6 years were included. RBF was assessed by testing meal-stimulated C-peptide concentrations. Information regarding severe hypoglycemia within the past year, current HbA1c, and daily insulin requirements was retrieved from the medical records and through patient interviews.Ninety-two children (27%) had RBF >0.04 nmol/L. Patients with RBF <0.04 nmol/L were significantly more likely to have severe hypoglycemia than patients with RBF >0.04 nmol/L (odds ratio, 2.59; 95% CI, 1.10-7.08; P < 0.03). HbA1c was significantly higher in patients with RBF <0.04 nmol/L compared with patients with RBF >0.04 nmol/L (mean, 8.49 ± 0.08% [69.3 ± 0.9 mmol/mol] vs. 7.92 ± 0.13% [63.1 ± 1.4 mmol/mol]; P < 0.01), and insulin requirements were significantly lower in patients with RBF >0.2 nmol/L (mean ± SE: 1.07 ± 0.02 vs. 0.93 ± 0.07 units/kg/day; P < 0.04).We demonstrated considerable phenotypic diversity in RBF among children after 3-6 years of type 1 diabetes. Children with RBF are at lower risk for severe hypoglycemia, have better diabetes regulation, and have lower insulin requirements compared with children without RBF. There appears to be a lower limit for stimulated RBF of ∼0.04 nmol/L that confers a beneficial effect on hypoglycemia and metabolic control.
Whole-body and segmental bioelectrical parameters in chronic liver disease: Effect of gender and disease stages
Authors: Carmine Panella, Francesco William Guglielmi, Tecla Mastronuzzi, Antonio Francavilla
Journal: Hepatology (1995)

The aim of this study was to examine and compare whole-body and segmental impedance measurements in control subjects and patients with progression of liver disease and to investigate whole-body and segmental bioelectrical changes occurring during dehydration therapy or paracentesis. Males have lower resistance (R) and reactance (Xc) values than females in measurements both of the whole body and of the arm, leg, and trunk. This is not true in patients. In the three groups of patients, whole-body R and Xc were lower in each increased disease stage, suggesting that stage has a significant main effect on impedance measurements. The lower extremities were the segment most influenced by the progression of liver disease. The sum of the arm and leg R was only slightly lower than the value of whole-body resistance. The trunk has a meager influence on this parameter, as is clearly shown by the absence of variations before and immediately after paracentesis. In edematous cirrhotic patients without ascites treated with diuretics, our data also showed a significant correlation (r = .81; SEE = 1.2) between changes in body weight (BW) and in the bioelectrical evaluation of total body water (TBW). The association of a prevalent increment of Xc (approximately 40%) with a reduction of extracellular water is the most significant bioelectrical event during dehydration therapy. All these findings show that impedance measurements have a low sensitivity in detecting the volume of ascites in cirrhotic patients, whereas Xc has a clinical use in monitoring changes in extracellular water (EW).
Capsaicin cough receptor sensitivity test in children
Authors: AB Chang, PD Phelan, RG Roberts, CF Robertson
Journal: European Respiratory Journal (1996)

Capsaicin has been used as a tussive agent in studies in adults to determine cough receptor sensitivity. The aim of this study was to determine the tolerance, repeatability and influence of inspiratory flow on the capsaicin cough receptor sensitivity test in children. Thirty children (mean age 11 yrs; range 6-16 yrs) were tested on two different days, to determine the lowest concentration of capsaicin required to stimulate two or more coughs (cough threshold (Cth)), 2-4 coughs (C2), and five or more coughs (C5). Capsaicin was nebulized through a dosimeter, with an arrangement that allowed the subjects to visualize and regulate their inspiratory flow. Using a constant inspiratory flow of 20 L x min(-1), tests were reproducible for C2, C5 and Cth (doubling dose changes of 1.13, 1.03 and 1.08, respectively). An increase in the inspiratory flow from 20 to 60 L x min(-1) significantly increased C2 (19.5 to 46.8 microM; p=0.016) and C5 (46.8 to 128.8 microM; p=0.008). We conclude that in children, the capsaicin cough challenge test: 1) is well-tolerated; 2) is highly repeatable; and that 3) the inspiratory flow significantly influences cough receptor sensitivity and repeatability of the test and should, thus, be regulated.
Recent advances in cutaneous angiogenesis
Authors: M. Bhushan, H.S. Young, P.E.C. Brenchley, C.E.M. Griffiths
Journal: British Journal of Dermatology (2002)

An understanding of the molecular basis of angiogenesis is key to the appreciation of many of the advances made in the field of neovascularization over the past two decades. The sequence of events involved in angiogenesis includes: (i) increased vascular permeability and leakage; (ii) degradation of basement membrane; (iii) endothelial cell proliferation and migration through the surrounding extracellular matrix; and (iv) maturation and stabilization of the newly formed vessel bed. This review provides an update on the molecular basis of such pathways in the skin, with particular emphasis on the endothelial cell‐specific vascular endothelial growth factor and angiopoietins as modulators of angiogenesis that can be targeted in therapy of cutaneous disease.
Left Ventricular Volume Reduction by Radiofrequency Heating of Chronic Myocardial Infarction in Patients With Congestive Heart Failure
Authors: Octavio A. Victal, John R. Teerlink, Efrain Gaxiola, Arthur W. Wallace, Sergio Najar, David H. Camacho, Augustin Gutierrez, Gabriel Herrera, Gustavo Zuniga, Fausto Mercado-Rios, Mark B. Ratcliffe
Journal: Circulation (2002)

Myocardial infarct expansion and left ventricular (LV) remodeling are integral components in the evolution of chronic heart failure and predict morbidity and mortality. Radiofrequency (RF) heating and patch placement of chronic LV aneurysms caused a sustained reduction in LV infarct area and volume in an ovine infarct model. This study evaluated the effect of RF heating and epicardial patch as an adjunct to coronary artery bypass graft on LV volumes in patients with prior myocardial infarction, evidence of akinetic/dyskinetic scar, and LV ejection fraction < or =40%.Ten patients (3 female; mean age, 64+/-11 years) scheduled for coronary artery bypass graft were enrolled (Canadian Cardiovascular Society angina class 2.1+/-1.1; New York Heart Association class 3.1+/-0.5). Intraoperative digital photography demonstrated an acute 39% reduction in infarct area (n=5; P=0.01), and transesophageal ECGs demonstrated a 16% acute reduction in LV end-diastolic volumes (n=9; P=0.002) after RF treatment. There were no intraoperative or procedure-related postoperative complications, and during an average follow-up of >180 days, there have been no safety issues. All patients had complete relief of their angina and improvement in exercise tolerance. Serial transthoracic ECGs over the 6 months of follow-up after RF treatment demonstrated persistent reductions in LV end-diastolic volume (29%; P<0.0001) and LV end-systolic volume (37%; P<0.0001) with improved ejection fraction (P<0.02).RF heating and patch placement in these 10 patients resulted in acute reduction in infarct area and ventricular volumes that were maintained 180 days after procedure. This technique may reduce the incidence of congestive heart failure and mortality in these patients and warrants investigation in larger clinical trials.
Effects of Carbon Monoxide Inhalation during Experimental Endotoxemia in Humans
Authors: Florian B. Mayr, Alexander Spiel, Judith Leitner, Claudia Marsik, Peter Germann, Roman Ullrich, Oswald Wagner, Bernd Jilma
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Data show that carbon monoxide (CO) exerts direct antiinflammatory effects in vitro and in vivo after LPS challenge in a mouse model. We hypothesized that CO may act as an antiinflammatory agent in human endotoxemia. The aim of this trial was to study the effects of CO inhalation on cytokine production during experimental human endotoxemia. The main study was a randomized, double-blinded, placebo-controlled, two-way cross-over trial in healthy volunteers. Each volunteer inhaled synthetic air (as placebo) and 500 ppm CO for 1 hour in random order with a washout period of 6 weeks and received a 2-ng/kg intravenous bolus of LPS after inhalation. Carboxyhemoglobin levels were assessed as a safety parameter. CO inhalation increased carboxyhemoglobin levels from 1.2% (95% confidence interval, 1.0 to 1.4%) to peak values of 7.0% (95% confidence interval, 6.5 to 7.7%). LPS infusion transiently increased plasma concentrations of tumor necrosis factor-alpha, interleukin (IL)-6 (approximately 150-fold increases), and IL-8, as well as IL-1alpha and IL-1beta mRNA levels (an approximately 200-fold increase). These LPS-induced changes were not influenced by CO inhalation. Inhalation of 500 ppm CO for 1 hour had no antiinflammatory effects in a systemic inflammation model in humans, as 250 ppm for 1 hour did in rodents.
Influence of the third generation pill controversy on prescriptions for oral contraceptives among first time users: population based study
Authors: L. de Jong-van den Berg
Journal: BMJ (2003)

Women taking oral contraceptives containing gestodene or desogestrel (the so called third generation oral contraceptives) have a higher risk of venous thrombosis than women taking a second generation pill.1 After the first publication on the subject, in 1995,2 the discussion in Dutch medical journals was conservative; prescribing physicians were advised to not alarm women who did not have a risk of deep vein thrombosis, be cautious in the prescribing of third generation oral contraceptives to young women who start taking the oral contraceptive pill, and encourage women at risk of deep vein thrombosis to change from taking a third generation pill to taking a second generation pill. 3 4 Many experts, …
Allergen-specific Th1 cells fail to counterbalance Th2 cell–induced airway hyperreactivity but cause severe airway inflammation
Authors: Gesine Hansen, Gerald Berry, Rosemarie H. DeKruyff, Dale T. Umetsu
Journal: Journal of Clinical Investigation (1999)

Allergic asthma, which is present in as many as 10% of individuals in industrialized nations, is characterized by chronic airway inflammation and hyperreactivity induced by allergen-specific Th2 cells secreting interleukin-4 (IL-4) and IL-5. Because Th1 cells antagonize Th2 cell functions, it has been proposed that immune deviation toward Th1 can protect against asthma and allergies. Using an adoptive transfer system, we assessed the roles of Th1, Th2, and Th0 cells in a mouse model of asthma and examined the capacity of Th1 cells to counterbalance the proasthmatic effects of Th2 cells. Th1, Th2, and Th0 lines were generated from ovalbumin (OVA)-specific T-cell receptor (TCR) transgenic mice and transferred into lymphocyte-deficient, OVA-treated severe combined immunodeficiency (SCID) mice. OVA-specific Th2 and Th0 cells induced significant airway hyperreactivity and inflammation. Surprisingly, Th1 cells did not attenuate Th2 cell–induced airway hyperreactivity and inflammation in either SCID mice or in OVA-immunized immunocompetent BALB/c mice, but rather caused severe airway inflammation. These results indicate that antigen-specific Th1 cells may not protect or prevent Th2-mediated allergic disease, but rather may cause acute lung pathology. These findings have significant implications with regard to current therapeutic goals in asthma and allergy and suggest that conversion of Th2-dominated allergic inflammatory responses into Th1-dominated responses may lead to further problems.
IMMUNIZATION EXPERIMENTS WITH SWINE INFLUENZA VIRUS
Authors: Richard E. Shope
Journal: The Journal of Experimental Medicine (1936)

1. Swine influenza virus obtained from the lungs of infected ferrets or mice, when administered intramuscularly or subcutaneously, immunizes swine to swine influenza. 2. Ferrets, which have received subcutaneous injections of swine influenza virus obtained from the lungs of infected ferrets, are immune to intranasal infection with this virus. Similar injections with virus from the lungs of infected mice or swine do not immunize. 3. Mice can be immunized to intranasal infection with swine influenza virus by the subcutaneous injection of virus obtained from the lungs of infected mice, but not by similar injection with virus from the lungs of infected ferrets or swine. Repeated injections induce greater immunity than a single one. 4. Intraperitoneal inoculation of both mice and ferrets with swine influenza virus immunizes them to intranasal infection and it appears to make little or no difference whether the virus used as vaccine is obtained from the lungs of infected mice, ferrets, or swine. 5. Field experiments in which swine influenza followed the intramuscular administration of virus are cited as examples of the hazard involved in the use of this means of immunization in a densely crowded susceptible population.
Bacterial and fungal microbiota in relation to probiotic therapy (VSL#3) in pouchitis
Authors: T Kuhbacher
Journal: Gut (2006)

<b>Background:</b> The intestinal microbiota plays a critical role in the pathophysiology of pouchitis, a major complication after ileal pouch anal anastomosis in patients with ulcerative colitis. Recently, controlled trials have demonstrated that probiotics are effective in maintenance of remission in pouchitis patients. However, the mechanism by which therapy with probiotics works remains elusive. This study explores the role of the bacterial and fungal flora in a controlled trial for maintenance of remission in pouchitis patients with the probiotic VSL#3 compound. <b>Methods:</b> The mucosa associated pouch microbiota was investigated before and after therapy with VSL#3 by analysis of endoscopic biopsies using ribosomal DNA/RNA based community fingerprint analysis, clone libraries, real time polymerase chain reaction (PCR), and fluorescence in situ hybridisation. Patients were recruited from a placebo controlled remission maintenance trial with VSL#3. <b>Results:</b> Patients who developed pouchitis while treated with placebo had low bacterial and high fungal diversity. Bacterial diversity was increased and fungal diversity was reduced in patients in remission maintained with VSL#3 (p = 0.001). Real time PCR experiments demonstrated that VSL#3 increased the total number of bacterial cells (p = 0.002) and modified the spectrum of bacteria towards anaerobic species. Taxa specific clone libraries for <i>Lactobacilli</i> and <i>Bifidobacteria</i> showed that the richness and spectrum of these bacteria were altered under probiotic therapy. <b>Conclusions:</b> Probiotic therapy with VSL#3 increases the total number of intestinal bacterial cells as well as the richness and diversity of the bacterial microbiota, especially the anaerobic flora. The diversity of the fungal flora is repressed. Restoration of the integrity of a “protective” intestinal mucosa related microbiota could therefore be a potential mechanism of probiotic bacteria in inflammatory barrier diseases of the lower gastrointestinal tract.
Infections in the male genital tract and reactive oxygen species
Authors: F R Ochsendorf
Journal: Human Reproduction Update (1999)

In the male genital tract, reactive oxygen species (ROS) are generated by spermatozoa and leukocytes including neutrophils and macrophages. ROS are involved in the regulation of sperm functions such as capacitation and the acrosome reaction. Infections lead to an excessive ROS production, resulting in an 'oxidative burst' from neutrophils/macrophages as a first-line defence mechanism. This is modulated by several cytokines and the pro-oxidant mechanisms of bacteria and viruses. At the site of an infection, the degree of activation of leukocytes, i.e. the amount of ROS produced, and the available antioxidative systems determine whether spermatozoa are damaged or not. During an infection, an imbalance of pro- and antioxidants favouring the former result in oxidative stress which impairs the sperm functions mentioned, as well as motility and fertilization. ROS produced during infections of the testis and epididymis are especially harmful to spermatozoa due to the longer contact time and the lack of antioxidant protection. In the final ejaculate, only very high numbers of ROS-producing leukocytes are detrimental to sperm functions. An infectious injury involving ROS in the prostate gland, seminal vesicles of epididymis could impair sperm functions indirectly. Pro- and antioxidative properties of therapeutics are currently receiving more attention as part of anti-infectious therapies. At present, there are many unresolved questions concerning the exact role of ROS during infections of the male genital tract because of the difficulty of specifically assessing the site of generation and the short-lived effects of ROS. New techniques may enable specific studies to fill this gap in the near future.
Downstream molecular pathways of FLT3 in the pathogenesis of acute myeloid leukemia: biology and therapeutic implications
Authors: Shinichiro Takahashi
Journal: Journal of Hematology & Oncology (2011)

FLT3 is a type III receptor tyrosine kinase. Mutations of FLT3 comprise one of the most frequently identified types of genetic alterations in acute myeloid leukemia. One-third of acute myeloid leukemia patients have mutations of this gene, and the majority of these mutations involve an internal tandem duplication in the juxtamembrane region of FLT3, leading to constitutive activation of downstream signaling pathways and aberrant cell growth. This review summarizes the current understanding of the effects of the downstream molecular signaling pathways after FLT3 activation, with a particular focus on the effects on transcription factors. Moreover, this review describes novel FLT3-targeted therapies, as well as efficient combination therapies for FLT3-mutated leukemia cells.
Long-Term Evaluation of Ifosfamide-Related Nephrotoxicity in Children
Authors: Odile Oberlin, Oumaya Fawaz, Annie Rey, Patrick Niaudet, Vita Ridola, Daniel Orbach, Christophe Bergeron, Annie Sophie Defachelles, Jean-Claude Gentet, Claudine Schmitt, Hervé Rubie, Martine Munzer, Dominique Plantaz, Anne Deville, Veronique Minard, Nadège Corradini, Guy Leverger, Florent de Vathaire
Journal: Journal of Clinical Oncology (2009)

Ifosfamide is widely used in pediatric oncology but its nephrotoxicity may become a significant issue in survivors. This study is aimed at evaluating the incidence of late renal toxicity of ifosfamide and its risk factors.Of the 183 patients prospectively investigated for renal function, 77 treated for rhabdomyosarcoma, 39 for other soft tissue sarcoma, 39 for Ewing's sarcoma, and 28 for osteosarcoma were investigated at least 5 years after treatment. No patients had received cisplatin and/or carboplatin. Glomerular and tubular functions were graded according to the Skinner system.The median dose of ifosfamide was 54 g/m(2) (range, 18 to 117 g/m(2)). After a median follow-up of 10 years, 89.5% of patients had normal tubular function, and 78.5% had normal glomerular function rate (GFR). Serum bicarbonate and calcium were normal in all patients. Hypomagnesemia was observed in 1.2% and hypophosphatemia in 1%. The tubular threshold for phosphate was reduced in 24% of the patients (grade 1 in 15%, grade 2 in 8%, and grade 3 in 0.5%). Glycosuria was detected in 37% of the patients but was more than 0.5 g/24 hours in only 5%. Proteinuria was observed in 12%. Ifosfamide dose and interval from therapy to investigations were predictors of tubulopathy in univariate and multivariate analysis. In a multivariate analysis, an older age at diagnosis and the length of interval since treatment had independent impacts on the risk of abnormal GFR.Renal toxicity is moderate with a moderate dose of ifosfamide. However, since it can be permanent and can get worse with time, repeated long-term evaluations are important, and this risk should be balanced against efficacy.