tbuckley/cabot-search huggingface dataset:
Nod1-Mediated Endothelial Cell Activation by <i>Chlamydophila pneumoniae</i>
Authors: Bastian Opitz, Stefanie Förster, Andreas C. Hocke, Matthias Maass, Bernd Schmeck, Stefan Hippenstiel, Norbert Suttorp, Matthias Krüll
Journal: Circulation Research (2005)

Seroepidemiological and animal studies, as well as demonstration of viable bacteria in atherosclerotic plaques, have linked Chlamydophila pneumoniae infection to development of chronic vascular lesions and coronary heart disease. Inflammation and immune responses are dependent on host recognition of invading pathogens. The recently identified cytosolic Nod proteins are candidates for intracellular recognition of bacteria, such as the obligate intracellular chlamydia. In the present study, mechanisms of endothelial cell activation by C . pneumoniae via Nod proteins were examined. Viable, but not heat-inactivated, chlamydia activated human endothelial cells, suggesting that invasion of these cells is necessary for their profound activation. Endothelial cells express Nod1. Nod1 gene silencing by small interfering RNA reduced C pneumoniae –induced IL-8 release markedly. Moreover, in HEK293 cells, overexpressed Nod1 or Nod2 amplified the capacity of C pneumoniae to induce nuclear factor κB (NF-κB) activation. Interestingly, heat-inactivated bacteria were still able to induced a NF-κB reporter gene activity via Nod proteins when transfected intracellularly, but not when provided from the extracellular side. In contrast, TLR2 sensed extracellular heat-inactivated chlamydia. In conclusion, we demonstrated that C pneumoniae induced a Nod1-mediated and Nod2-mediated NF-κB activation in HEK293 cells. In endothelial cells, Nod1 played a dominant role in triggering a chlamydia-mediated inflammatory process.
Multimarker Strategy for Short-Term Risk Assessment in Patients With Dyspnea in the Emergency Department
Authors: Luc W. Eurlings, Sandra Sanders-van Wijk, Roland van Kimmenade, Aart Osinski, Lidwien van Helmond, Maud Vallinga, Harry J. Crijns, Marja P. van Dieijen-Visser, Hans-Peter Brunner-La Rocca, Yigal M. Pinto
Journal: Journal of the American College of Cardiology (2012)
Autosomal Dominant Pseudohypoaldosteronism Type 1
Authors: David S. Geller, Junhui Zhang, Maria-Christina Zennaro, Alberto Vallo-Boado, Juan Rodriguez-Soriano, Laszlo Furu, Robert Haws, Daniel Metzger, Barbara Botelho, Lefkothea Karaviti, Andrea M. Haqq, Howard Corey, Sandra Janssens, Pierre Corvol, Richard P. Lifton
Journal: Journal of the American Society of Nephrology (2006)

Autosomal dominant pseudohypoaldosteronism type 1 (adPHA1) is a rare condition that is characterized by renal resistance to aldosterone, with salt wasting, hyperkalemia, and metabolic acidosis. It is thought of as a mild disorder; affected children's symptoms respond promptly to salt therapy, and treatment is not required after childhood. Mutations in the mineralocorticoid receptor gene (MR) cause adPHA1, but the long-term consequences of MR deficiency in humans are not known. Herein are described six novel adPHA1-causing MR mutations (four de novo) and evidence that haploinsufficiency of MR is sufficient to cause adPHA1. Furthermore, genotype-phenotype correlation is reported in a large adPHA1 kindred. A number of cases of neonatal mortality in infants who were at risk for adPHA1 were identified; coupled with the frequent identification of de novo mutations in affected individuals, this suggests that the seemingly benign adPHA1 may have been a fatal neonatal disorder in previous eras, preventing propagation of disease alleles. In contrast, it is shown that adult patients with adPHA1 are clinically indistinguishable from their wild-type relatives except for presumably lifelong elevation of renin, angiotensin II, and aldosterone levels. These data highlight the critical role of MR in the maintenance of salt homeostasis early in life and illuminate the sodium dependence of pathologic effects of renin and angiotensin II. They furthermore argue that nongenomic effects of aldosterone play no significant role in the long-term development of cardiovascular disease.
Obstructive sleep apnoea in the elderly: role of continuous positive airway pressure treatment
Authors: Miguel Ángel Martínez-García, Eusebi Chiner, Luis Hernández, Jose Pascual Cortes, Pablo Catalán, Silvia Ponce, Jose Ramón Diaz, Ester Pastor, Laura Vigil, Carmen Carmona, Josep Maria Montserrat, Felipe Aizpuru, Patricia Lloberes, Mercedes Mayos, Maria José Selma, Jose Fernando Cifuentes, Alvaro Muñoz
Journal: European Respiratory Journal (2015)

Almost all the information about the effect of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnoea (OSA) comes from clinical trials involving only middle-aged patients. The objective of this study was to assess the effect of CPAP treatment in elderly patients with severe OSA on clinical, quality-of-life and neurocognitive spheres. We performed an open-label, randomised, multicentre clinical trial in a consecutive clinical cohort of 224 elderly (≥70 years old) patients with confirmed severe OSA (apnoea-hypopnea index ≥30) randomised to receive CPAP (n=115) or no CPAP (n=109) for 3 months. A sleep study was performed by either full polysomnography or respiratory polygraphy. CPAP titration was performed by an autoCPAP device. The primary endpoint was quality of life (Quebec Sleep Questionnaire) and secondary endpoints included sleep-related symptoms, presence of anxiety/depression, office-based blood pressure and some neurocognitive tests. The mean±sd age was 75.5±3.9 years. The CPAP group achieved a greater improvement in all quality-of-life domains (p<0.001; effect size: 0.41-0.98), sleep-related symptoms (p<0.001; effect size 0.31-0.91) as well as anxiety (p=0.016; effect size 0.51) and depression (p<0.001; effect size: 0.28) indexes and some neurocognitive tests (digit symbol test (p=0.047; effect size: 0.20) and Trail Making Test A (p=0.029; effect size: 0.44)) in an intention-to-treat analysis. In conclusion, CPAP treatment resulted in an improvement in quality of life, sleep-related symptoms, anxiety and depression indexes and some neurocognitive aspects in elderly people with severe OSA.
Montelukast plus cetirizine in the prophylactic treatment of seasonal allergic rhinitis: influence on clinical symptoms and nasal allergic inflammation
Authors: M. Kurowski, P. Kuna, P. Górski
Journal: Allergy (2004)

The aim of our study was to investigate effects of 6-week pretreatment of seasonal allergic rhinitis (AR) with cetirizine, and montelukast, alone and in combination. Antihistamine/antileukotriene treatment is effective in AR. Antihistamines may prevent AR symptoms while prophylactic activity of antileukotrienes remains unclear.Sixty AR patients, aged 18-35 years, were randomized to receive placebo, montelukast only, cetirizine only, or montelukast plus cetirizine, 6 weeks prior and 6 weeks after the beginning of grass pollen season. Mean self-recorded in-season symptom scores and mean weekly all-symptom scores were analyzed. In 31 patients, nasal lavages were performed before treatment, and at the end of the study, i.e. 12 weeks after the treatment initiation. Eosinophil and basophil counts, eosinophil cationic protein (ECP), and mast cell tryptase (MCT) levels were evaluated in lavage samples.Combined montelukast/cetirizine pretreatment significantly reduced in-season symptom score for sneezing, eye itching, nasal itching, rhinorrhea, and congestion. Montelukast plus cetirizine were more effective than cetirizine alone in preventing eye itching, rhinorrhea, and nasal itching. Moreover, combined pretreatment with montelukast and cetirizine delayed appearance of AR symptoms. Eosinophil nasal lavage fluid counts were significantly increased during pollen season in placebo and montelukast-only groups. No differences were observed in basophil counts. The in-season ECP level was significantly increased in all groups except montelukast-plus-cetirizine group. In-season MCT levels were not increased.Combined antihistamine and antileukotriene treatment started 6 weeks before the pollen season is effective in preventing AR symptoms and reduces allergic inflammation in nasal mucosa during natural allergen exposure.
JNK1 activation predicts the prognostic outcome of the human hepatocellular carcinoma
Authors: Qingshan Chang, Jianguo Chen, Kevin J Beezhold, Vince Castranova, Xianglin Shi, Fei Chen
Journal: Molecular Cancer (2009)

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with an extremely poor prognosis. The classification of HCC based on the molecular signature is not well-established. Results In the present study, we reported HCC signature genes based on the JNK1 activation status in 31 HCC specimens relative to the matched distal noncancerous liver tissue from 31 patients. The HCCs with high JNK1 (H-JNK1) and low JNK1 (L-JNK1) were sub-grouped. Two different signature gene sets for both H-JNK1 and L-JNK1 HCC were identified through gene expression profiling. A striking overlap of signature genes was observed between the H-JNK1 HCC and the hepatoblastoma or hepatoblastoma-type HCC. Many established biomarkers for hepatic progenitor cells were over-expressed in H-JNK1 HCC, including AFP, TACSTD1, KRT19, KRT7, THY1, and PROM1. In addition, the majority of the most up-regulated genes were those associated with metastasis and earlier recurrence, whereas the genes for normal liver function were substantially down-regulated in H-JNK1 HCC tissue. A Kaplan-Meier plot demonstrated that the survival of the patients with H-JNK1 HCC was severely impaired. Conclusion Accordingly, we believe that the H-JNK1 HCC may originate from hepatic progenitor cells and is associated with poorer prognosis. The status of JNK1 activation in HCC tissue, thus, might be a new biomarker for HCC prognosis and therapeutic targeting.
Nitroglycerin and Heterogeneity of Myocardial Blood Flow REDUCED SUBENDOCARDIAL BLOOD FLOW AND VENTRICULAR CONTRACTILE FORCE
Authors: Robert Forman, Edward S. Kirk, James M. Downey, Edmund H. Sonnenblick
Journal: Journal of Clinical Investigation (1973)

The effects of both intracoronary and intravenous administration of nitroglycerin on transmural distribution of blood flow in the left ventricle after partial coronary artery occlusion was investigated using two independent methods. In 16 open chest, anesthetized dogs, tubing supplying the cannulated left coronary artery was partially occluded. Strain gauges sutured paralled to superficial and deep fibers of the myocardium separately recorded the contractile force of each layer. With occlusion set so that depression of the deep contractile force was imminent. 12 mug intracoronary nitroglycerin in seven dogs depressed only the deep contractile force without changing systemic hemodynamics. Intravenous administration of 180 mug nitroglycerin in nine dogs resulted in a decrease of deep contractile force and aortic pressure often associated with an increase in superficial contractile force. Distribution of myocardial blood flow during peak coronary flow after intracoronary administration of nitroglycerin or during a decrease in aortic pressure after intravenous nitroglycerin administration was determined by the tissue uptake of an intracoronary bolus of rubidium-(80). This was compared with the uptake of potassium-(42) injected before nitroglycerin. Intravenous or intracoronary administration of nitroglycerin caused a significant reduction in subendocardial blood flow with a decrease in the subendocardial/subepicardial ratio of isotope. These experiments suggest that under conditions of acute partial coronary occlusion, the autoregulatory response results in more fully dilated subendocardial vessels causing them to be less responsive to nitroglycerin. Nitroglycerin may then reduce the vascular resistance in the subepicardial more than the subendocardial vessels, resulting in a "steal" of blood flow from deep to superficial myocardium.
Double-Blind Study of Clozapine Dose Response in Chronic Schizophrenia
Authors: George M. Simpson, Richard C. Josiassen, Joseph K. Stanilla, Jose de Leon, Chand Nair, George Abraham, Aruby Odom-White, Ralph M. Turner
Journal: American Journal of Psychiatry (1999)

This study explored the relative efficacy of three different doses of clozapine.Fifty patients who met Kane et al.'s criteria for treatment-refractory schizophrenia or schizoaffective disorder were studied. All subjects were randomly assigned to 100, 300, or 600 mg/day of clozapine for 16 weeks of double-blind treatment. Forty-eight patients completed this first 16 weeks. Of the 50 patients, 36 went on to second and third 16-week trials of double-blind treatment at the remaining doses.Four subjects (8%) responded to the first 16-week condition, and one subject (2%) responded to the next 16-week crossover condition. A chi-square comparison of the response rates from the three dose groups failed to show a significant effect. An analysis of variance (ANOVA) comparison of Brief Psychiatric Rating Scale-Anchored (BPRS-A) total change scores from baseline to last observation carried forward showed a significant dose effect (600>300>100 mg/day) at 16 weeks of treatment. A crossover ANOVA of the BPRS-A total scores from the 48-week study also showed that the main effect for dose was highly significant; the 100-mg/day dose gave the higher (poorer) values, and the 300- and 600-mg/ day doses gave equal (better) values. Gender played a role in clinical response to treatment at 100 mg/day.Clozapine treatment at 100 mg/day was less effective than at 300 or 600 mg/day. At 100 mg/day, women responded better than did men. The 600 mg/day group had the best results, but an occasional patient required up to 900 mg/day. Overall response rates were lower than expected.
Underdiagnosis of asthma: is the doctor or the patient to blame? The DIMCA project
Authors: C P van Schayck
Journal: Thorax (2000)

It is important to diagnose asthma at an early stage as early treatment may improve the prognosis in the long term. However, many patients do not present at an early stage of the condition so the physician may have difficulty with the diagnosis. A study was therefore undertaken to compare the proportion of patients who underpresented their respiratory symptoms with the proportion of underdiagnosed cases of asthma by the general practitioner (GP). A secondary aim was to investigate whether bad perception of dyspnoea by the patient was a determining factor in the underpresentation of asthma symptoms to the GP.A random sample of 1155 adult subjects from the general population in the eastern part of the Netherlands was screened for respiratory symptoms and lung function and the results were compared with the numbers of asthma related consultations registered in the medical files of the GP. In subjects with reduced lung function the ability to perceive dyspnoea was investigated during a histamine provocation test in subjects who did and did not report their symptoms to their GP.Of the random sample of 1155 subjects 86 (7%) had objective airflow obstruction (forced expiratory volume in one second (FEV(1)) below the reference value corrected for age, length, and sex minus 1.64SD on two occasions) and had symptoms suggestive of asthma. Of these 86 subjects only 29 (34%) consulted the GP, which indicates underpresentation by 66% of patients. Of all subjects with objective airflow obstruction who presented to their GP with respiratory symptoms, 23 (79%) were recorded in the medical files as having asthma, indicating underdiagnosis by the GP in 21% of cases. Of the subjects with objective airflow obstruction who visited the GP with respiratory symptoms 6% had bad perception of dyspnoea compared with 26% of those who did not present to the GP in spite of airflow obstruction (chi(2) = 3.02, p = 0.08).Underpresentation to GPs of respiratory symptoms by asthmatic patients contributes significantly to the problem of underdiagnosis of asthma. Underdiagnosis by the GP seems to play a smaller role. Furthermore, there are indications that underpresentation of symptoms by the patient is at least partly explained by a worse perception of dyspnoea.
Heterotachy and Tree Building: A Case Study with Plastids and Eubacteria
Authors: Peter Lockhart, Phil Novis, Brook G. Milligan, Jamie Riden, Andrew Rambaut, Tony Larkum
Journal: Molecular Biology and Evolution (2005)

The nature of heterotachy at the center of recent controversy over the relative performance of tree-building methods is different from the form of heterotachy that has been inferred in empirical studies. The latter have suggested that proportions of variable sites (pvar) vary among orthologues and among paralogues. However, the strength of this inference, describing what may be one of the most important evolutionary properties of sequence data, has remained weak. Consequently, other models of sequence evolution have been proposed to explain some long-branch attraction (LBA) problems that could be attributed to differences in pvar. For an empirical case with plastid and eubacterial RNA polymerase sequences, we confirm using capture-recapture estimates and simulations that pvar can differ among orthologues in anciently diverged evolutionary lineages. We find that parsimony and a least squares distance method that implements an overly simple model of sequence evolution are susceptible to LBA induced by this form of heterotachy. Although homogeneous maximum likelihood inference was found to be robust to model misspecification in our specific example, we caution against assuming that it will always be so.
Apoptosis in lung injury and fibrosis
Authors: F. Drakopanagiotakis, A. Xifteri, V. Polychronopoulos, D. Bouros
Journal: European Respiratory Journal (2008)

Pulmonary fibrosis is characterised by fibroblast accumulation and alveolar epithelium denudation. Increased apoptosis of alveolar epithelial cells and decreased apoptosis of fibroblasts may play an important role in the pathogenesis of disease. Inflammatory cells can modulate apoptosis of other cell types, both by removal of apoptotic debris and by cytokine production, thus preserving a pro-fibrotic environment. In the present review, some of the mechanisms by which apoptosis may contribute to the pathogenesis of idiopathic pulmonary fibrosis are described.
Lymphocytic colitis: a retrospective clinical study of 199 Swedish patients
Authors: M Olesen
Journal: Gut (2004)

<b>Background:</b> Lymphocytic colitis is characterised by chronic diarrhoea and specific microscopic changes in a macroscopically normal colonic mucosa. We report clinical features and treatment outcome in a large patient cohort. <b>Methods:</b> Patients were searched for in 24 Swedish gastroenterology clinics. The biopsy material was reassessed using strict histopathological criteria. Clinical data were obtained from medical notes. <b>Results:</b> Lymphocytic colitis was diagnosed in 199 cases. The female:male ratio was 2.4:1. Median age at diagnosis was 59 (48–70) years. The most frequent symptoms were diarrhoea (96%), abdominal pain (47%), and weight loss (41%). The course was chronic intermittent in 30% of patients, chronic continuous in 7%, and a single attack in 63%, and in these cases the disease duration was 6 (4–11) months. Seventy nine (40%) patients reported associated diseases, of which thyroid disorders, coeliac disease, and diabetes mellitus were the most common. In 34 first or second degree relatives of 24 (12%) patients, a family history of ulcerative colitis, Crohn’s disease, collagenous colitis, or coeliac disease was reported. Drug induced disease was suspected in 19 (10%) patients. A non-significant peak of disease onset was seen in December-January. More than 80% of treated patients improved on corticosteroids, including budesonide. <b>Conclusions:</b> A family history of other bowel disorders is a new finding. The sudden onset and single attack of limited duration may support a possible infectious cause in some cases. Drugs may cause lymphocytic colitis.
Aetiological factors in attempted suicide.
Authors: S. Greer, J. C. Gunn, K. M. Koller
Journal: BMJ (1966)

In recent years there have been major advances in our understanding of attempted suicide. In particular, several important studies have thrown light upon the psychopathology and social effects (Stengel, Cook, and Kreeger, 1958), epidemiology (Schneidman and Farberow, 1961 ; Kessel, 1965; Parkin and Stengel, 1965), and prognosis (Dahlgren, 1945; Schneider, 1954; Riiegsegger, 1963) of this behaviour disturbance. Less satisfactory, however, is the present state of knowledge concerning the causes. This is not surprising, since the difficulties of studying the manifold circumstances which may contribute to suicidal behaviour are formidable. But a legitimate criticism is that, hitherto, reported findings have been based almost entirely on uncontrolled observations. Thus the aetiological significance of suggested predisposing factors, which include physical and mental illness, social isolation and disorganization, interpersonal conflicts, and parental deprivation in childhood, remains obscure in the absence of similar data for nonsuicidal controls. It is evident that suicidal behaviour results from the complex interaction of a variety of adverse circumstances in the life of any given individual. Furthermore, these predisposing factors will vary considerably from person to person. Nevertheless, it
Patient Comparison of Sensory Attributes of Olopatadine and Azelastine Nasal Sprays
Authors: E.O. Meltzer, W.E. Berger, S.J. Chadwick, G. Gross, C.F. LaForce, R. Garadi, K. Crenshaw, G.M. Wall
Journal: Journal of Allergy and Clinical Immunology (2007)
Supporting Family Caregivers at the End of Life
Authors: Michael W. Rabow, Joshua M. Hauser, Jocelia Adams
Journal: JAMA (2004)

Even for patients receiving complex, intensive medical care for serious and life-threatening illness, family caregiving is typically at the core of what sustains patients at the end of life. The amorphous relationship between physicians and the families of patients at the end of life presents both challenges and opportunities for which physicians may be unprepared. Families play important roles in the practical and emotional aspects of patient care and in decision making at the end of life. At the same time, family members may carry significant burdens as a result of their work. Through the perspectives of the wife, daughter, and home care nurse of a patient who died from pancreatic cancer, we illustrate the range of family caregiver experiences and suggest potentially helpful physician interventions. We describe 5 burdens of family caregiving (time and logistics, physical tasks, financial costs, emotional burdens and mental health risks, and physical health risks) and review the responsibilities of physicians to family caregivers. Based on available evidence, we identify 5 areas of opportunity for physicians to be of service to family members caring for patients at the end of life, including promoting excellent communication with family, encouraging appropriate advance care planning and decision making, supporting home care, demonstrating empathy for family emotions and relationships, and attending to family grief and bereavement. In caring well for family caregivers at the end of life, physicians may not only improve the experiences of patients and family but also find greater sustenance and meaning in their own work.