tbuckley/cabot-search huggingface dataset:
Beyond Efficacy: The STAR*D Trial
Authors: Thomas R. Insel
Journal: American Journal of Psychiatry (2006)

Psychiatrists have a range of treatments to offer patients with depression.Randomized controlled trials have demonstrated the efficacy of tricyclic antidepressants, SSRIs, cognitive behavior therapy, and interpersonal therapy.For each of these interventions, one can say with some confidence that at least 40% of a cohort with depression will show statistically significant reductions in unbiased ratings of depression.This information, while entirely commendable in the world of research, is far from satisfactory in the world of practice where an individual clinician needs to make treatment decisions to help an individual patient.The practical questions that the clinician might ask include: For this specific patient, what is the best of the available treatments?What magnitude of response can my patient realistically expect in 4 or 6 weeks?And what should I do if my patient is not sufficiently better in this period: continue or switch treatments?If the first treatment does not work, what is the next best option?So what does this approach tell us?This first report of the STAR*D trial includes only Phase 1 results (N=2,876) but already provides important, practical answers.First, only about 30% of patients met criteria for remission during citalopram treatment.For remission, the mean dose of citalopram (41.8 mg/day) was higher and the mean duration of treatment (47 days with 5.5 visits) was longer than might have been expected on the basis of current clinical practice.
Randomized Trial of Amifostine in Locally Advanced Non–Small-Cell Lung Cancer Patients Receiving Chemotherapy and Hyperfractionated Radiation: Radiation Therapy Oncology Group Trial 98-01
Authors: Benjamin Movsas, Charles Scott, Corey Langer, Maria Werner-Wasik, Nicos Nicolaou, Ritsuko Komaki, Mitchell Machtay, Colum Smith, Rita Axelrod, Linda Sarna, Todd Wasserman, Roger Byhardt
Journal: Journal of Clinical Oncology (2005)

To test the ability of the cytoprotectant, amifostine, to reduce chemoradiotherapy-induced esophagitis and evaluate its influence on quality of life (QOL) and swallowing symptoms.A total of 243 patients with stage II to IIIA/B non-small-cell lung cancer received induction paclitaxel 225 mg/m(2) intravenously (IV) days 1 and 22 and carboplatin area under the curve (AUC) days 1 and 22, followed by concurrent weekly paclitaxel (50 mg/m(2) IV) and carboplatin (AUC 2), and hyperfractionated radiation therapy (69.6 Gy at 1.2 Gy bid). Patients were randomly assigned at registration to amifostine (AM) 500 mg IV four times per week or no AM during chemoradiotherapy. Beyond standard toxicity end points, physician dysphagia logs (PDLs), daily patient swallowing diaries, and QOL (EORTC QLQ-C30/LC-13) were also collected. Swallowing AUC analyses were calculated from patient diaries and PDLs.A total of 120 patients were randomly assigned to receive AM, and 122, to receive no AM (one patient was ineligible); 72% received AM per protocol or with a minor deviation. AM was associated with higher rates of acute nausea (P = .03), vomiting (P = .007), cardiovascular toxicity (P = .0001), and infection or febrile neutropenia (P = .03). The rate of >/= grade 3 esophagitis was 30% with AM versus 34% without AM (P = .9). Patient diaries demonstrated lower swallowing dysfunction AUC with amifostine (z test P = .025). QOL was not significantly different between the two arms, except for pain, which showed more clinically meaningful improvement and less deterioration at 6 weeks follow-up (v pretreatment) in the AM arm (P = .003). The median survival rates for both arms were comparable (AM, 17.3 v no AM, 17.9 months; P = .87).AM did not significantly reduce esophagitis >/= grade 3 in patients receiving hyperfractionated radiation and chemotherapy. However, patient self-assessments suggested a possible advantage to AM that is being explored with modified dosing route strategies.
Prognostic impact of sleep disordered breathing and its treatment in heart failure: an observational study
Authors: Clemens Jilek, Marion Krenn, Daniela Sebah, Ruth Obermeier, Astrid Braune, Victoria Kehl, Stephan Schroll, Sylvia Montalvan, Günter A.J. Riegger, Michael Pfeifer, Michael Arzt
Journal: European Journal of Heart Failure (2010)
Enhanced expression of vascular endothelial growth factor in lungs of newborn infants with congenital diaphragmatic hernia and pulmonary hypertension
Authors: S. M K Shehata, W. J Mooi, T. Okazaki, I. El-Banna, H. S Sharma, D. Tibboel
Journal: Thorax (1999)

Pulmonary hypoplasia accompanied by pulmonary hypertension resistant to treatment is an important feature of congenital diaphragmatic hernia (CDH). The pathogenesis of the pulmonary vascular abnormalities in CDH remains to be elucidated at the molecular level. Vascular endothelial growth factor (VEGF), an endothelial cell specific mitogen, is known to play a role in pulmonary angiogenesis and vascular remodelling but there are no data on VEGF expression in patients with CDH.Necroscopic lung specimens from 21 patients with CDH with lung hypoplasia and from seven age matched control newborn infants without lung hypoplasia were processed for immunohistochemical analysis using affinity purified anti-human VEGF antibodies. All the cases of CDH had pulmonary hypoplasia, indicated by a lung/body weight index of </=0.012, and pulmonary hypertension indicated by repeated cardiac ultrasonography. Cellular localisation of VEGF was semiquantitatively analysed using a staining score ranging from 0 (no staining) to 4 (very strong staining).Significantly raised levels of VEGF immunoreactivity were observed in lung specimens from cases of CDH compared with controls. VEGF was detected mainly in the bronchial epithelium and the medial smooth muscle cells of large (>200 microm) and small (<200 microm) pulmonary arteries, the most intense staining being in the medial smooth muscle cells of the small pulmonary arteries. Endothelial cells were positive for VEGF staining in patients with CDH but not in controls.This is the first study of VEGF expression in newborn infants with CDH. Increased levels of VEGF, especially in the small, pressure regulating pulmonary arteries, point to a potential role in vascular remodelling. This may reflect an unsuccessful attempt by the developing fetus to increase the pulmonary vascular bed in the hypoplastic lungs to alleviate the associated pulmonary hypertension.
Enhanced Startle Reactions to Acoustic Stimuli in Patients With Obsessive-Compulsive Disorder
Authors: Veena Kumari, Hossein Kaviani, Peter W. Raven, Jeffrey A. Gray, Stuart A. Checkley
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Anxiety states induced experimentally or occurring naturally potentiate the startle reflex elicited by sudden sensory stimuli in both animals and human beings. The authors investigated whether patients with obsessive-compulsive disorder (OCD) show exaggerated startle reactions to acoustic probes, especially during negative-affect-toned stimuli, compared with healthy subjects. METHOD: Ten patients with OCD and 10 age- and sex-matched comparison subjects were shown a series of film clips. Two of the film clips had positive valence, two had negative valence, and two had relatively neutral valence. The subjects' eyeblink startle response was measured in reaction to startle-eliciting stimuli presented three times binaurally during each film clip. RESULTS: Patients with OCD produced larger startle reflexes and shorter latencies to onset of startle response than the comparison subjects over the entire session. CONCLUSIONS: Patients with OCD were excessively responsive to startle-eliciting stimuli. This effect may be associated with the development or maintenance of OCD.
Echocardiographic abnormalities in patients with COPD at their first hospital admission
Authors: Xavier Freixa, Karina Portillo, Carles Paré, Judith Garcia-Aymerich, Federico P. Gomez, Marta Benet, Josep Roca, Eva Farrero, Jaume Ferrer, Carlos Fernandez-Palomeque, Josep M. Antó, Joan Albert Barberà
Journal: European Respiratory Journal (2012)

Cardiovascular disease accounts for significant morbidity and mortality in chronic obstructive pulmonary disease (COPD). Its prevalence and mechanisms of association have not been elucidated. The study aimed to assess the prevalence of echocardiographic abnormalities and potential risk factors in patients with COPD at their first exacerbation requiring hospital admission. Transthoracic echocardiography was prospectively performed in 342 patients (forced expiratory volume in 1 s 52 ± 16% predicted) 3 months after discharge. Significant cardiac alterations were present in 64% of patients; 27% left- and 48% right-heart disorders. The most common were right ventricle enlargement (30%) and pulmonary hypertension (19%). Left ventricle enlargement was present in 6%, left ventricle systolic dysfunction in 13%, left ventricle diastolic impairment in 12% and left atrial dilatation in 29%. Echocardiographic abnormalities were unrelated to COPD severity and were more frequent in patients with self-reported cardiac disease. They were also observed in 63% of patients with no known cardiac disease or cardiovascular risk factors other than smoking. We conclude that cardiac abnormalities are highly prevalent in COPD patients at the time of their first severe exacerbation, even in the absence of established cardiac disease or cardiovascular risk factors. Considering the prognostic and therapeutic implications of cardiac comorbidity, echocardiography should be considered in the assessment of patients with clinically significant COPD.
Specific inhibition of lymphokine biosynthesis and autocrine growth using antisense oligonucleotides in Th1 and Th2 helper T cell clones.
Authors: A Harel-Bellan, S Durum, K Muegge, A K Abbas, W L Farrar
Journal: The Journal of Experimental Medicine (1988)

T helper cells have recently been divided into two subsets. The Th1 subset secretes and responds to IL-2 in an autocrine manner. The Th2 subset upon mitogen or antigen stimulation releases IL-4. Here we describe a novel technology that allowed us to confirm this distinction. We have used synthetic oligonucleotides complementary to the 5' end of mouse IL-2 and IL-4 to specifically block the biosynthesis of IL-2 or IL-4 in two murine helper T cell clones from the Th1 or Th2 subset. We show that the antisense IL-2 oligonucleotide inhibited the proliferation of the Th1 clone and had no effect on the Th2 clone. In parallel experiments, the antisense IL-4 oligonucleotide blocked the proliferation of the Th2 clone and not the proliferation of the Th1 clone. The inhibition was significantly reversed in both cases by the addition of the relevant lymphokine (IL-2 in the case of the Th1 clone, IL-4 in the case of the Th2 clone). Northern analysis, using cDNA probes specific for the two lymphokines, showed a decrease in the steady-state level of the relevant lymphokine mRNA, suggesting the specific degradation of the mRNA by an RNase H-like enzymatic activity. This strategy, which allows the specific blockade of the biosynthesis of a lymphokine, could be useful for future studies on the role of each T helper subset in physiological immune responses.
Gender and mortality following hospitalisation for COPD
Authors: A. Fahim, W. Y. Lee, S. Faruqi, J. A. Kastelik
Journal: Thorax (2011)

We read with interest the article by Gonzalez et al 1 on gender differences in survival following hospitalisation of chronic obstructive pulmonary disease (COPD) patients in a large cohort of a Canadian population. There are limited data on gender differences and mortality in COPD. Despite women having worse dyspnoea and health status, they appear to have a lower mortality rate than men.2 The study conducted by Gonzalez and coworkers demonstrated an interesting finding of a significantly better mean survival and time to rehospitalisation in female patients. We conducted a study of …
Response to Emotional Stimuli in Boys With Conduct Disorder
Authors: Sabine C. Herpertz, Bodo Mueller, Mutaz Qunaibi, Christiane Lichterfeld, Kerstin Konrad, Beate Herpertz-Dahlmann
Journal: American Journal of Psychiatry (2005)

Boys with conduct disorder are at risk of persistently showing antisocial behavior in adult life, particularly if they have an additional diagnosis of attention deficit hyperactivity disorder (ADHD). In the search for biological risk factors that predispose children to the development of antisocial personality disorder, research has provided substantial data suggesting that autonomic hyporesponsiveness indicates a greater likelihood of future antisocial behavior. The purpose of this study was to examine autonomic arousal in boys with conduct disorder, comorbid conduct disorder and ADHD, and ADHD only.In addition to self-ratings, electrodermal responses to pleasant, neutral, and unpleasant slides were obtained for 21 boys with conduct disorder and 54 boys with ADHD plus conduct disorder. Forty-three boys with a diagnosis of ADHD only were recruited as a clinical comparison group, and 43 boys with no conduct disorder or ADHD were included as a healthy comparison group. All subjects were ages 8-13 years.Compared to the healthy subjects and the subjects with ADHD only, the boys with conduct disorder and with ADHD plus conduct disorder reported lower levels of emotional response to aversive stimuli and lower autonomic responses to all slides independent of valence.Although the self-report data supported a deficit in reactivity to explicit fear cues, the psychophysiological data indicated that boys with conduct disorder both with and without a comorbid condition of ADHD are characterized by a generalized deficit in autonomic responsivity in an experimental situation in which children were exposed to complex visual stimuli of unpredictable affective quality. Psychophysiological findings may point to a deficit in associative information processing systems that normally produce adaptive cognitive-emotional reactions.
Reducing Medical Errors and Adverse Events
Authors: Julius Cuong Pham, Monica S. Aswani, Michael Rosen, HeeWon Lee, Matthew Huddle, Kristina Weeks, Peter J. Pronovost
Journal: Annual Review of Medicine (2011)

Medical errors account for ∼98,000 deaths per year in the United States. They increase disability and costs and decrease confidence in the health care system. We review several important types of medical errors and adverse events. We discuss medication errors, healthcare-acquired infections, falls, handoff errors, diagnostic errors, and surgical errors. We describe the impact of these errors, review causes and contributing factors, and provide an overview of strategies to reduce these events. We also discuss teamwork/safety culture, an important aspect in reducing medical errors.
Some Observations on the Co-ordination of Diaphragmatic and Rib Movement in Respiration
Authors: H. Herxheimer
Journal: Thorax (1949)

Diaphragm and intercostal muscles together ventilate the lungs.Little is known about the pro- portion in which they share in this work.Such knowledge, however, is necessary if we want to understand the aetiology of certain respiratory disorders.An attempt has been made, therefore, to investigate the part played by diaphragm and intercostal muscles in the exchange of air. METHODTracings of the respiration were made with a spiromefer of the Benedict-Roth type to which a flowmeter was attached.Oxygen was supplied continuously through this flowmeter at the same rate at which it disappeared from the spirometer.The tracings were thus kept horizontal.After quiet breathing had been recorded for some minutes the subject was asked,to inhale and exhale fully, and the vital capacity was OF
Postnatal Changes in Response to Norepinephrine in the Normal and Pulmonary Hypertensive Lung
Authors: Margrid B. Schindler, Alison A. Hislop, Sheila G. Haworth
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

The effect of norepinephrine administration on pulmonary blood flow during the neonatal period is unclear. Therefore, norepinephrine responses were studied in isolated pulmonary arteries, pulmonary veins, and femoral arteries taken from normal pigs from birth to adulthood and from pigs subjected to chronic hypoxia either from birth for 3 days or from 3 to 14 days of age. Normally, the contractile response of pulmonary arteries and veins to norepinephrine decreased after birth (p < 0.01), and α2-adrenoceptor–mediated relaxation increased in pulmonary arteries and veins and in femoral arteries. Hypoxic exposure from birth prevented the normal postnatal reduction in pulmonary arterial contractile response, nor was there a postnatal increase in pulmonary arterial adrenoceptor–mediated relaxation. When hypoxic exposure followed a period of normal adaptation, the pulmonary arterial contractile response was not enhanced, but relaxation was significantly impaired. The response of pulmonary veins and femoral arteries was not affected by hypoxic exposure. The contractile effect of norepinephrine was 15- to 60-fold greater in isolated systemic arteries than in pulmonary arteries taken from both normal and pulmonary hypertensive piglets at all ages. This suggests that use of norepinephrine to manage systemic hypotension in infants and children will not compromise the pulmonary vasculature.
Emerging Paradigms in Cardiomyopathies Associated With Cancer Therapies
Authors: Bonnie Ky, Pimprapa Vejpongsa, Edward T.H. Yeh, Thomas Force, Javid J. Moslehi
Journal: Circulation Research (2013)

The cardiovascular care of cancer patients (cardio-oncology) has emerged as a new discipline in clinical medicine, given recent advances in cancer therapy, and is driven by the cardiovascular complications that occur as a direct result of cancer therapy. Traditional therapies such as anthracyclines and radiation have been recognized for years to have cardiovascular complications. Less expected were the cardiovascular effects of targeted cancer therapies, which were initially thought to be specific to cancer cells and would spare any adverse effects on the heart. Cancers are typically driven by mutations, translocations, or overexpression of protein kinases. The majority of these mutated kinases are tyrosine kinases, though serine/threonine kinases also play key roles in some malignancies. Several agents were developed to target these kinases, but many more are in development. Major successes have been largely restricted to agents targeting human epidermal growth factor receptor-2 (mutated or overexpressed in breast cancer), BCR-ABL (chronic myelogenous leukemia and some cases of acute lymphoblastic leukemia), and c-Kit (gastrointestinal stromal tumor). Other agents targeting more complex malignancies, such as advanced solid tumors, have had successes, but have not extended life to the degree seen with chronic myelogenous leukemia. Years before the first targeted therapy, Judah Folkman correctly proposed that to address solid tumors one had to target the inherent neoangiogenesis. Unfortunately, emerging evidence confirms that angiogenesis inhibitors cause cardiac complications, including hypertension, thrombosis, and heart failure. And therein lies the catch-22. Nevertheless, cardio-oncology has the potential to be transformative as the human cardiomyopathies that arise from targeted therapies can provide insights into the normal function of the heart.
Circulating plasma concentrations of atrial natriuretic peptide and catecholamines in response to maximal exercise in normal and asthmatic subjects.
Authors: G Hulks, A F Mohammed, A G Jardine, J M Connell, N C Thomson
Journal: Thorax (1991)

BACKGROUND: Intravenous infusion of atrial natriuretic peptide has been shown to cause bronchodilatation in patients with asthma and endogenous atrial natriuretic peptide is known to rise with exercise. Whether an aberration in release of atrial natriuretic peptide is concerned in the pathogenesis of exercise induced bronchoconstriction has not been studied. METHODS: The atrial natriuretic peptide response to exercise was studied in eight men with exercise induced asthma and eight age matched non-asthmatic men. Subjects exercised to exhaustion on a treadmill, using the Bruce protocol. Atrial natriuretic peptide and catecholamines were measured at the end of each stage of exercise and oxygen consumption and heart rate were monitored throughout. RESULTS: Both groups showed a 3.5 fold increase in plasma atrial natriuretic peptide during exercise (mean (SE): normal subjects 25 (4) pmol/l; asthmatic subjects 24 (5) pmol/l), with no difference between the two groups. There was a close correlation between plasma atrial natriuretic peptide concentrations and oxygen uptake, catecholamine release, and heart rate in both groups. The catecholamine response was similar in the asthmatic and normal subjects, both groups showing a four fold rise in plasma adrenaline and a 4-5 fold rise in plasma noradrenaline. CONCLUSION: A defect in the release of circulating atrial natriuretic peptide does not account for exercise induced asthma; the concentrations of the circulating peptide that were achieved may effect a small reduction in airway reactivity. Our data do not support the idea that asthmatic patients have abnormal sympathoadrenal activity.
Advancing donor liver age and rapid fibrosis progression following transplantation for hepatitis C
Authors: M Wali, R F Harrison, P J Gow, D Mutimer
Journal: Gut (2002)

Cirrhosis with liver failure due to hepatitis C virus (HCV) infection is the most common indication for liver transplantation (LT). Reinfection of the transplanted liver by HCV is inevitable, and aggressive hepatitis with accelerated progression to graft cirrhosis may be observed. Of concern, recent reports suggest that the outcome of LT for HCV may have deteriorated in recent years. Determinants of rate of progression to cirrhosis in the immunocompetent non-transplant patient are well defined, and the most powerful determinant is patient age at the time of infection. Following LT for HCV, recipient age does not affect outcome of HCV reinfection. However, the impact of donor age on graft fibrosis progression rate following LT has not been examined.We have examined post-transplant biopsies to assess histological activity, including fibrosis stage (scored 0-6 units, 6 representing established cirrhosis), and to calculate fibrosis progression rates in 101 post-transplant specimens from 56 HCV infected LT patients. Univariate and multivariate analyses examined the impact of parameters including recipient and donor age and sex on fibrosis progression rate, and on predicted time to cirrhosis.For the cohort, median fibrosis progression rate was 0.78 units/year, and median interval from transplantation to development of cirrhosis was 7.7 years. In multivariate analysis, donor age (not recipient age) was a powerful determinant (p=0.02) of fibrosis progression rate. When the liver donor was younger than 40 years, median progression rate was 0.6 units/year and interval to cirrhosis was 10 years. When the donor was aged 50 years or more, median progression rate was 2.7 units/year and interval to cirrhosis only 2.2 years. During the observation period there has been a significant increase in donor age (p=0.01) but date of transplantation per se is not a determinant of progression rate when included in multivariate analyses.Donor age has a major influence on graft outcome following transplantation for HCV. The changing organ donor profile will affect the long term results of LT for HCV. These observations have important implications for donor liver allocation.