tbuckley/cabot-search huggingface dataset:
Recombinant Human Superoxide Dismutase Enhances the Effect of Inhaled Nitric Oxide in Persistent Pulmonary Hypertension
Authors: ROBIN H. STEINHORN, GEORGE ALBERT, DANIEL D. SWARTZ, JAMES A. RUSSELL, CAROLYN R. LEVINE, JONATHAN M. DAVIS
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

We investigated the pulmonary vascular effects of superoxide dismutase (SOD) alone and in combination with inhaled nitric oxide (iNO) in newborn lambs with persistent pulmonary hypertension (PPHN) following prenatal ligation of the ductus arteriosus. In in vitro experiments, pretreatment with SOD significantly enhanced vascular relaxation in response to the NO donor S-nitrosyl-acetylpenicillamine (SNAP) in fifth-generation pulmonary arteries isolated from lambs with PPHN. In vivo treatment of fully instrumented newborn lambs with a single intratracheal dose of recombinant human CuZn SOD (rhSOD; 5 mg / kg) produced selective dilation of the pulmonary circulation. Further studies, of the combination of rhSOD and iNO, showed enhancement of the pulmonary vascular effects of iNO after brief periods of inhalation of 5 ppm and 80 ppm NO. We conclude that rhSOD reduces pulmonary vascular resistance and facilitates the action of iNO in a lamb model of PPHN. This suggests that rhSOD may prove to be an effective adjunctive treatment for newborns with PPHN.Keywords: lung; newborn; pulmonary artery; free radical scavengers
Randomized Clinical Trial of Telephone-Administered Cognitive-Behavioral Therapy to Reduce Post-Traumatic Stress Disorder and Distress Symptoms After Hematopoietic Stem-Cell Transplantation
Authors: Katherine N. DuHamel, Catherine E. Mosher, Gary Winkel, Larissa E. Labay, Christine Rini, Yeraz Markarian Meschian, Jane Austin, Paul B. Greene, Catalina R. Lawsin, Anna Rusiewicz, Celia L. Grosskreutz, Luis Isola, Craig H. Moskowitz, Esperanza B. Papadopoulos, Scott Rowley, Eileen Scigliano, Jack E. Burkhalter, Karen E. Hurley, Andreas R. Bollinger, William H. Redd
Journal: Journal of Clinical Oncology (2010)

A significant number of survivors of hematopoietic stem-cell transplantation (HSCT) report enduring adverse effects of treatment, including illness-related post-traumatic stress disorder (PTSD) symptoms and general distress. We report results of a randomized clinical trial that tested the effects of a 10-session, telephone-administered cognitive-behavioral therapy (CBT) intervention on PTSD, depression, and distress symptoms.Survivors who had undergone HSCT 1 to 3 years earlier (N = 408) were assessed for study eligibility. Those who met study eligibility criteria (n = 89) completed a baseline assessment that included a clinical interview and self-report measures of PTSD symptoms (the primary outcome) and depression and general distress (the secondary outcomes). Next, they were randomly assigned to CBT or an assessment-only condition. Survivors in the CBT group completed 10 individual telephone-based CBT sessions (T-CBT) that included strategies to reduce PTSD symptoms, depression, and general distress. Follow-up assessments occurred at 6, 9, and 12 months after the baseline assessment.Linear mixed-model analyses revealed that, compared with HSCT survivors in the assessment-only condition, survivors who completed T-CBT reported fewer illness-related PTSD symptoms, including less avoidance (P < .001) and fewer intrusive thoughts (P < .05) as well as less general distress and fewer depressive symptoms (P < .05) even after controlling for potential demographic and medical covariates. These results were consistent across the three follow-up assessments.A brief, telephone-administered CBT intervention developed for HSCT survivors is an efficacious treatment for reducing illness-related PTSD symptoms and general distress.
Mapping Geographic Zones of Cancer Risk with Epigenetic Biomarkers in Normal Breast Tissue
Authors: Pearlly S. Yan, Chinnambally Venkataramu, Ashraf Ibrahim, Joseph C. Liu, Rulong Z. Shen, Nils M. Diaz, Barbara Centeno, Frank Weber, Yu-Wei Leu, Charles L. Shapiro, Charis Eng, Timothy J. Yeatman, Tim H.-M. Huang
Journal: Clinical Cancer Research (2006)

Genetic alterations were previously identified in normal epithelia adjacent to invasive cancers. The aim of this study was to determine DNA methylation in histologically normal tissues from multiple geographic zones adjacent to primary breast tumors.First, methylation status of a 4-kb region of RASSF1A promoter was interrogated using oligonucleotide-based microarray in 144 samples (primary tumors, 47; adjacent normals, 69; reduction mammoplasty tissues, 28). Second, allelic imbalance (AI)/loss of heterozygosity (LOH) surrounding RASSF1A promoter were analyzed in 30 samples (tumors, 8; adjacent normals, 22). Third, global methylation screening of 49 samples (tumors, 12; adjacent normals, 25; reduction mammoplasty, 12) was done by differential methylation hybridization. Real-time quantitative methylation-specific PCR was used to validate the microarray findings.DNA methylation in the core RASSF1A promoter was low in reduction mammoplasty tissues (P=0.0001) when compared with primary tumors. The adjacent normals had an intermediate level of methylation. The regions surrounding the core were highly methylated in all sample types. Microsatellite markers showed AI/LOH in tumors and some of the adjacent normals. Concurrent AI/LOH and DNA methylation in RASSF1A promoter occurred in two of six tumors. Global methylation screening uncovered genes more methylated in adjacent normals than in reduction mammoplasty tissues. The methylation status of four genes was confirmed by quantitative methylation-specific PCR.Our findings suggest a field of methylation changes extending as far as 4 cm from primary tumors. These frequent alterations may explain why normal tissues are at risk for local recurrence and are useful in disease prognostication.
Kinetics of Tempol for Prevention of Xerostomia Following Head and Neck Irradiation in a Mouse Model
Authors: Ana P. Cotrim, Anastasia L. Sowers, Beatrijs M. Lodde, Joseph M. Vitolo, Albert Kingman, Angelo Russo, James B. Mitchell, Bruce J. Baum
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Radiotherapy is commonly used to treat the majority of patients with head and neck cancers. Salivary glands in the radiation field are dramatically affected by this procedure. The purpose of this study was to examine pharmacokinetic characteristics of the stable nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) with respect to radioprotection of the salivary glands. Experimental Design: To evaluate the effect of different doses and times of administration, the heads of C3H mice were exposed to a single irradiation dose of 15 Gy, with i.p. tempol injection. To analyze other routes of administration, we injected 275 mg/kg tempol by an i.m., i.v., or s.c. route, 10 minutes before irradiation. We also tested whether oral administration of tempol in a topical form (either in a mouthwash or gel) provided any salivary gland protection. Results: Tempol treatment (137.5 or 275 mg/kg, i.p., 10 minutes before irradiation) significantly reduced irradiation-induced salivary hypofunction (∼50-60%). I.v. or s.c. administration of tempol also showed significant radioprotection, whereas i.m. administration proved to be ineffective. Topical use of tempol, either as a mouthwash or gel, also was radioprotective. Conclusions: Our results strongly suggest that tempol is a promising candidate for clinical application to protect salivary glands in patients undergoing radiotherapy for head and neck cancers.
Functional analysis of human T cell subsets defined by monoclonal antibodies. IV. Induction of suppressor cells within the OKT4+ population.
Authors: Y Thomas, L Rogozinski, O H Irigoyen, S M Friedman, P C Kung, G Goldstein, L Chess
Journal: The Journal of Experimental Medicine (1981)

In this report, we explored the functional heterogeneity within the OKT4+ subset of human T cells. Evidence was obtained that although in vitro pokeweed mitogen-activated OKT4+ cells can function as radioresistant helper cells, these activated OKT4+ cells could also exert potent feedback suppression. Despite the induction of suppressor cells after pokeweed mitogen activation, the OKT4+ population maintains its original OKT3+, OKT4+, nd OKT8- surface phenotype. The suppressor cells contained within the activated OKT4+ population were found to be radiosensitive. Importantly, the suppression mediated by activated OKT4+ cells required the presence of radiosensitive cells contained within the resting OKT4+ population. Taken together, these results suggest that the OKT4+ subset of human T cells contains cells that can be activated to differentiate into suppressor cells independent of OKT8+ cells.
Effect of MRCP introduction on ERCP practice: are there implications for service and training?
Authors: J T Jenkins
Journal: Gut (2006)

Training is an increasingly relevant issue in the UK.1 The structure of postgraduate medical training is undergoing significant change at present, with attempts to streamline and shorten duration. Modernising medical careers (MMC) marks a major reform in postgraduate medical education.2

Endoscopic retrograde cholangiopancreatography (ERCP) requires considerable training to perform effectively and safely.3 Competency has been based on total procedure numbers performed by trainees. Consensus suggests 180–200 diagnostic/therapeutic ERCPs are required to obtain competence within a training facility with sufficient case volume for viable training opportunities.2 Selective cannulation of the bile duct has been used as a benchmark for technical success.4 Moreover, multivariate analyses find case volume to independently predict ERCP related complications.5–8

“Diagnostic” ERCP should rarely be required with …
Role of multivitamins and mineral supplements in preventing infections in elderly people: systematic review and meta-analysis of randomised controlled trials
Authors: Alia El-Kadiki, Alexander J Sutton
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To evaluate the effectiveness of multivitamins and mineral supplements in reducing infections in an elderly population. <b>Design</b> Systematic review and meta-analysis of randomised controlled trials. <b>Data sources</b> Medline and other databases. Reference lists of identified articles were inspected for further relevant articles. <b>Selection of studies</b> Trials were included if they evaluated the effect of multivitamins and mineral supplements on infections in an elderly population. <b>Review methods</b> Studies were assessed for the methodological quality by using the Jadad instrument. If the data required for the analyses were not available from the published articles we requested them from the original study authors. Meta-analysis was undertaken on three outcomes: the mean difference in number of days spent with infection, the odds ratio of at least one infection in the study period, and the incidence rate ratio for the difference in infection rates. Data on adverse events were also extracted. <b>Results</b> Eight trials met our inclusion criteria. Owing to inconsistency in the outcomes reported, only a proportion of the trials could be included in each meta-analysis. Multivitamins and mineral supplements were found to reduce the mean annual number of days spent with infection (three studies) by 17.5 (95% confidence interval 11 to 24, P &lt; 0.001). The odds ratio for at least one infection in the study period (three studies) was 1.10 (0.81 to 1.50, P = 0.53). The infection rate ratio (four studies) was 0.89 (0.78 to 1.03, P = 0.11). Reporting of adverse events was poor. <b>Conclusion</b> The evidence for routine use of multivitamin and mineral supplements to reduce infections in elderly people is weak and conflicting. Study results are heterogeneous, and this is partially confounded by outcome measure.
Effect of an inhaled antihistamine on exercise-induced asthma.
Authors: J P Hartley, S G Nogrady
Journal: Thorax (1980)

The ability of the H1 receptor antagonist clemastine to prevent exercise-induced asthma (EIA) has been studied in 10 adult asthmatic subjects. Exercise was performed for eight minutes on a cycle ergometer on two occasions on each of two days. The first test each day was without premedication and the second was preceded by inhalation of 0.05% clemastine or saline placebo given single blind in random order. Ventilatory function was assessed by serial measurements of peak expiratory flow rate (PEFR) and forced expiratory volume in one second (FEV1). All four tests for each patient were closely matched in terms of oxygen uptake and total ventilation which were monitored throughout exercise. The response to exercise after clemastine or placebo has been compared both directly and in terms of the degree of protection afforded against EIA compared with the initial test on the same day. Clemastine was significantly better than placebo for both PEFR and FEV1. All 10 subjects had less EIA after clemastine, which suggests an important role for histamine in its production. Other mechanisms may also be involved to a variable degree in different individuals.
Plasmapheresis, Infection, and Renal Disease
Authors: J. Cohen
Journal: JAMA (1981)

<h3>To the Editor.—</h3> I read the report by Wing and associates (1980;244:2423) of their experience with patients receiving plasmapheresis for acute renal disease. We have recently completed a prospective study of the infective complications in 75 patients who required high-dose immunosuppression and intensive plasmapheresis (unpublished data), and our results are somewhat at variance with those described by Wing et al. Almost all of our patients had active nephritis, underlying antiglomerular basement membrane disease, polyarteritis, Wegener's granulomatosis, or systemic lupus erythematosus. They received a regimen of high-dose corticosteroids, cyclophosphamide, and azathioprine; 50 patients were treated additionally with plasmapheresis in the amount of 4 L/day (mean, 13 days; range, two to 45 days). There was no correlation between the incidence of infection and the duration of plasmapheresis in the group as a whole (r=.34). A further analysis was performed in 23 patients with major infective complications (serious opportunist infections and death owing
Animal cruelty: Definitions and sociology
Authors: Andrew Nicholas Rowan
Journal: Behavioral and Brain Sciences (2006)

The definition of cruelty used by the author is broad and ambiguous and does not distinguish between acts of sadism, abuse, and neglect that all lead to the suffering of other beings. Some of the research involving animal cruelty is reviewed with the aim of raising questions about the relevance of the pain–blood–death (PBD) complex described by Nell.
Risk of Thyroid Cancer After Exposure to 131 I in Childhood
Authors: Elisabeth Cardis, Ausrele Kesminiene, Victor Ivanov, Irina Malakhova, Yoshisada Shibata, Valeryi Khrouch, Vladimir Drozdovitch, Evaldas Maceika, Irina Zvonova, Oleg Vlassov, André Bouville, Guennadi Goulko, Masaharu Hoshi, Alexander Abrosimov, Jadvyga Anoshko, Larisa Astakhova, Sergey Chekin, Evgenyi Demidchik, Rosaria Galanti, Masahiro Ito, Elena Korobova, Evgenyi Lushnikov, Marat Maksioutov, Vladimir Masyakin, Alexander Nerovnia, Vladimir Parshin, Evgenyi Parshkov, Nikolay Piliptsevich, Aldo Pinchera, Semyon Polyakov, Nina Shabeka, Eero Suonio, Vanessa Tenet, Anatoli Tsyb, Shunichi Yamashita, Dillwyn Williams
Journal: JNCI Journal of the National Cancer Institute (2005)

After the Chernobyl nuclear power plant accident in April 1986, a large increase in the incidence of childhood thyroid cancer was reported in contaminated areas. Most of the radiation exposure to the thyroid was from iodine isotopes, especially 131I. We carried out a population-based case-control study of thyroid cancer in Belarus and the Russian Federation to evaluate the risk of thyroid cancer after exposure to radioactive iodine in childhood and to investigate environmental and host factors that may modify this risk.We studied 276 case patients with thyroid cancer through 1998 and 1300 matched control subjects, all aged younger than 15 years at the time of the accident. Individual doses were estimated for each subject based on their whereabouts and dietary habits at the time of the accident and in following days, weeks, and years; their likely stable iodine status at the time of the accident was also evaluated. Data were analyzed by conditional logistic regression using several different models. All statistical tests were two-sided.A strong dose-response relationship was observed between radiation dose to the thyroid received in childhood and thyroid cancer risk (P<.001). For a dose of 1 Gy, the estimated odds ratio of thyroid cancer varied from 5.5 (95% confidence interval [CI] = 3.1 to 9.5) to 8.4 (95% CI = 4.1 to 17.3), depending on the risk model. A linear dose-response relationship was observed up to 1.5-2 Gy. The risk of radiation-related thyroid cancer was three times higher in iodine-deficient areas (relative risk [RR]= 3.2, 95% CI = 1.9 to 5.5) than elsewhere. Administration of potassium iodide as a dietary supplement reduced this risk of radiation-related thyroid cancer by a factor of 3 (RR = 0.34, 95% CI = 0.1 to 0.9, for consumption of potassium iodide versus no consumption).Exposure to (131)I in childhood is associated with an increased risk of thyroid cancer. Both iodine deficiency and iodine supplementation appear to modify this risk. These results have important public health implications: stable iodine supplementation in iodine-deficient populations may substantially reduce the risk of thyroid cancer related to radioactive iodines in case of exposure to radioactive iodines in childhood that may occur after radiation accidents or during medical diagnostic and therapeutic procedures.
The Connexin40 A96S Mutation Causes Renin-Dependent Hypertension
Authors: Indra Lübkemeier, Katharina Machura, Lisa Kurtz, Björn Neubauer, Radek Dobrowolski, Frank Schweda, Charlotte Wagner, Klaus Willecke, Armin Kurtz
Journal: Journal of the American Society of Nephrology (2011)

Deletion of the gap-junction-forming protein connexin40 leads to renin-dependent hypertension in mice, but whether observed human variants in connexin40, such as A96S, promote hypertension is unknown. Here, we generated mice with the A96S variant in the mouse connexin40 gene. Although mice homozygous for the A96S mutations had normal expression patterns of connexin40 in the kidney, they were hypertensive, had sixfold higher plasma renin concentrations, and had 40% higher levels of renin mRNA than controls. Renin-expressing cells were aberrantly located outside the media layer of afferent arterioles, and increased renal perfusion pressure did not inhibit renin secretion from kidneys isolated from homozygous A96S mice. Treatment with a low-salt diet in combination with an ACE inhibitor increased renin mRNA levels, plasma renin concentrations, and the number of aberrantly localized renin-producing cells. Taken together, these findings suggest that the A96S mutation in connexin40 leads to renin-dependent hypertension in mice. Modulation of renin secretion by BP critically depends on functional connexin40; with the A96S mutation, the aberrant extravascular localization of renin-secreting cells in the kidney likely impairs the pressure-mediated inhibition of renin secretion.
Obstructive sleep apnoea and urine catecholamines in hypertensive males: a population-based study
Authors: A. Elmasry, E. Lindberg, J. Hedner, C. Janson, G. Boman
Journal: European Respiratory Journal (2002)

Studies addressing the relationship between obstructive sleep apnoea (OSA) and sympathoadrenal activity have been criticized for poor control of factors known to confound sympathetic function, including hypertension. The aim of this study was to investigate the relationship between OSA and urinary catecholamines in a population-based sample of hypertensive males. In 1994, 2,668 males aged 40–79 yrs answered a questionnaire regarding sleep disorders and somatic diseases. Of those who reported hypertension, an age-stratified sample of 116 was selected for monitoring of breathing during sleep and overnight urine analysis. Subjects with OSA, defined as apnoea-hypopnoea index ≥10·h −1 , had higher concentrations of urinary normetanephrine (182±57 versus 141±45 µmol·mol −1 creatinine, p&lt;0.001) and metanephrine (70±28 versus 61±28 µmol·mol −1 creatinine, p&lt;0.05) in comparison to subjects without OSA. In a multiple regression analysis, there was an association between variables of sleep-disordered breathing and normetanephrine and metanephrine concentrations, independent of major confounding factors. The authors concluded that, in a population-based sample of hypertensive males, obstructive sleep apnoea is associated with increased urinary concentrations of extraneuronal metabolites of catecholamines independent of major confounding factors, suggesting increased sympathoadrenal activity. Elevated sympathoadrenal activity may explain the increased cardiovascular morbidity associated with obstructive sleep apnoea.
Psychiatric Morbidity Following Injury
Authors: Meaghan L. O’Donnell, Mark Creamer, Phillipa Pattison, Christopher Atkin
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Accurate information regarding the psychopathological consequences of surviving traumatic injury is of great importance for effective health service design and planning. Regrettably, existing studies vary dramatically in reported prevalence rates of psychopathology within this population. The aim of this study was to identify the prevalence of psychiatric morbidity following severe injury by adopting a longitudinal design with close attention to optimizing the research methodology. METHOD: Consecutive admissions (N=363) to a level 1 trauma service, excluding those with moderate or severe traumatic brain injury, were assessed at three time periods: just before discharge and 3 and 12 months after their injury. Structured clinical interviews were used to assess anxiety disorders, depressive disorders, and substance use disorders. RESULTS: Posttraumatic stress disorder (PTSD) and major depressive disorder were the most frequent diagnoses at both 3 and 12 months, with 10% of participants meeting diagnostic criteria for each disorder at 12 months. Over 20% of the group met criteria for at least one psychiatric diagnosis 12 months after their injury. Comorbidity was common, with the most frequent being PTSD with major depressive disorder. CONCLUSIONS: Psychopathology following injury is a frequent and persistent occurrence. Despite the adoption of a rigorous and potentially conservative methodology, one-fifth of participants met criteria for one or more psychiatric diagnoses 12 months after their injury. These findings have major implications for injury health care providers.
A 61-Year-Old Man With Parkinson's Disease
Authors: H. Desmond Hayes
Journal: JAMA (1996)

<h3>To the Editor.</h3> —The discussion by Dr Olanow<sup>1</sup>of Parkinson disease (PD) was of interest to me. I suspect some of us nonneurologists may tend to delay the diagnosis, and thus the treatment, when the presenting symptoms lack the classic features. My concern about Dr H's management, however, centers around the use of sertraline as the antidepressant in conjunction with selegiline. Dr W raised this question, but Olanow's response could be interpreted as minimizing the likelihood of adverse effects. In my experience, the potentially serious effects from drug combinations that can result in the serotonin syndrome are not well recognized. Informal surveys of my colleagues tend to support this contention. An opportunity to increase readers' awareness of the potentially lethal serotonin syndrome should not be dismissed lightly. The serotonin syndrome is thought to be the result of increased serotonin activity in the central nervous system caused by the concurrent