tbuckley/cabot-search huggingface dataset:
Beneficial effects of pimobendan on exercise tolerance and quality of life in patients with heart failure. Results of a multicenter trial. The Pimobendan Multicenter Research Group.
Authors: S H Kubo, S Gollub, R Bourge, P Rahko, F Cobb, M Jessup, S Brozena, M Brodsky, P Kirlin, J Shanes
Journal: Circulation (1992)

BACKGROUND This multicenter trial was conducted to determine the efficacy and safety of pimobendan, an inotropic agent with calcium-sensitizing properties and activity as a phosphodiesterase inhibitor, in patients with heart failure. METHODS AND RESULTS One hundred ninety-eight ambulatory patients with symptoms of moderate to severe heart failure despite therapy with digitalis and diuretics with or without a single vasodilator were randomly assigned to receive either placebo (n = 49) or pimobendan (n = 149) in a double-blind fashion for 12 weeks. A dose range of pimobendan was used including 2.5 (n = 49), 5 (n = 51), or 10 mg/day (n = 49). One hundred fifty-eight (80%) patients were taking a converting enzyme inhibitor (CEI) and 28 (14%) patients were taking a non-CEI vasodilator. At end point, the 5-mg dose of pimobendan significantly increase exercise duration compared with placebo (121.6 +/- 19.1 seconds, p less than 0.001), whereas the 10-mg dose produced an increase of borderline significance (81.1 +/- 19.5 seconds, p = 0.05). Peak VO2 was significantly increased by 2.23 +/- 0.58 ml/kg/min in the 5-mg group (p less than 0.01 versus placebo). Furthermore, quality of life measured with the Minnesota Living With Heart Failure Questionnaire improved by 8.5 +/- 2.3 units in the 5-mg group compared with 1.3 +/- 2.2 units in the placebo group (p less than 0.01). There were a total of 23 all-cause hospitalizations in the placebo group, which was significantly greater compared with 33 in the three groups treated with pimobendan (p less than 0.01). There were no significant differences between the placebo and pimobendan groups with respect to changes in ejection fraction and plasma norepinephrine measured at baseline and at the completion of the 12-week study, proarrhythmic effect, or the number of patients with a significant adjustment in background therapy. Eleven patients died, including three (6%) on placebo and eight (5%) on pimobendan (p = NS). Among all adverse events, headache tended to be more common in the pimobendan groups compared with placebo, with the incidence increasing with dose (p less than 0.05). CONCLUSIONS These data demonstrate that pimobendan significantly increases exercise duration, peak VO2, and quality of life in patients with heart failure. Pimobendan appears to be useful adjunctive therapy when added to digitalis, diuretics, and vasodilators.
Facilitating closure of surgical defects on the lower legs with a simple knee-bend
Authors: W. Hussain, N.J. Mortimer, P.J.M. Salmon
Journal: British Journal of Dermatology (2009)

Conflicts of interest: none declared. Madam, The surgical treatment of malignant and premalignant cutaneous lesions below the knee provides a particular challenge to the dermatologist. Even relatively small surgical defects may be difficult to close primarily, due to the lack of tissue laxity in this region. Often a wound may be deemed unsuitable for primary closure or alternatively closed primarily but under significant tension, thereby increasing the risk of wound dehiscence. In actual fact, a not insignificant tissue reservoir does exist on the lower leg, namely the surrounding tissue and skin overlying the gastrocnemius. Frequently, however, due to the positioning of the patient during surgery (most commonly lying supine when operating on the anterior or lateral lower leg), this reservoir is compressed and subsequently not identified and utilized when the surrounding skin is assessed for laxity. A simple ‘knee‐bend’, however, is all that is required to access this reservoir (Fig. 1). In doing so, even relatively large defects on the lower legs may be closed primarily without significant wound tension making the tying of sutures problematic. We have found that combining the ‘knee‐bend’ with the placement of an initial ‘side‐by‐side’ buried subcuticular suture1 can make wound closure effortless. The manoeuvre also has utility on the posterior lower leg (Fig. 2). Here, we usually request the surgical assistant to support the elevated foot (or alternatively rest the elevated foot on pillows), making the knee‐bend as comfortable as possible for the patient.
Abnormal left ventricular structure and function are associated with new onset diabetes mellitus: the strong heart study
Authors: Jennifer E. Liu, David C. Robbins, Jay Sosenko, Vittorio Palmieri, Jonathan N. Bella, Mary J. Roman, Richard R. Fabsitz, Elisa T. Lee, Thomas K. Welty, Barbara V. Howard, Richard B. Devereux
Journal: Journal of the American College of Cardiology (2002)
Biological Diagnosis of Brain Disorders: The Future of the Brain Sciences
Authors: Barry I. Liskow
Journal: JAMA (1975)

This volume has the admirable goal of increasing understanding between basic and clinical neuroscientists. However, despite breadth of scope, presentation of very current material, and conscientious selection of contributors, the book is disappointing when judged by its implicit goals. If the clinician reading the book knows little of such research areas as contingent negative variation, importance of proteolipids in brain chemistry, computer models of learning, or other specialized topics relating to the brain sciences, he is unlikely to gain much understanding from this book. The basic scientist who already knows a great deal about one or more of these topics will probably not find anything he does not already know about his specialty, and he may even disagree with what is presented. Furthermore, he will find but little to relate his fields of interest to the other neuroscience subtopics discussed. The book is an example, perhaps a victim, of its
Phylogeny and Divergence Times in Pinaceae: Evidence from Three Genomes
Authors: Xiao-Quan Wang, David C. Tank, Tao Sang
Journal: Molecular Biology and Evolution (2000)

In Pinaceae, the chloroplast, mitochondrial, and nuclear genomes are paternally, maternally, and biparentally inherited, respectively. Examining congruence and incongruence of gene phylogenies among the three genomes should provide insights into phylogenetic relationships within the family. Here we studied intergeneric relationships of Pinaceae using sequences of the chloroplast matK gene, the mitochondrial nad5 gene, and the low-copy nuclear gene 4CL. The 4CL gene may exist as a single copy in some species of Pinaceae, but it constitutes a small gene family with two or three members in others. Duplication and deletion of the 4CL gene occurred at a tempo such that paralogous loci are maintained within but not between genera. Exons of the 4CL gene have diverged approximately twice as fast as the matK gene and five times more rapidly than the nad5 gene. The partition-homogeneity test indicates that the three data sets are homogeneous. A combined analysis of the three gene sequences generated a well-resolved and strongly supported phylogeny. The combined phylogeny, which is topologically congruent with the three individual gene trees based on the Templeton test, is likely to represent the organismal phylogeny of Pinaceae. This phylogeny agrees to a certain extent with previous phylogenetic hypotheses based on morphological, anatomical, and immunological data. Disagreement between the previous hypotheses and the three-genome phylogeny suggests that morphology of both vegetative and reproductive organs has undergone convergent evolution within the pine family. The strongly supported monophyly of Nothotsuga longibracteata, Tsuga mertensiana, and Tsuga canadensis on all three gene phylogenies provides evidence against previous hypotheses of intergeneric hybrid origins of N. longibracteata and T. mertensiana. Divergence times of the genera were estimated based on sequence divergence of the matK gene, and they correspond well with the fossil record.
One in four hospital patients should be cared for out of hospital
Authors: I. Torjesen
Journal: BMJ (2011)

At least a quarter of hospital inpatients should be cared for at home rather than in hospital, the leader of the body that represents NHS managers has said.

Outlining the challenges the NHS will face in the coming year, Mike Farrar, chief executive of the NHS Confederation, the organisation that represents NHS managers, warned that the NHS needed to let go of the “outdated hospital or bust model of care” and to shift resources into community based services, early intervention, and self care.

The confederation believes that at …
Diagnosis of autism: Adequate funding is needed for assessment services
Authors: I. McClure
Journal: BMJ (2004)

Diagnosis of autism Adequate funding is needed for assessment services2][3] One important additional reason for such provision, which their review does not emphasise, is that well coordinated, multiagency assessment teams for autism spectrum disorders have a better chance of accurately not giving a diagnosis of it.Our multiagency assessment service for autism spectrum disorders has seen 57 patients in the past two years.We request baseline speech and language therapy and (where applicable) educational psychology assessments on the likelihood of autism spectrum disorder in all cases before patients are seen by our team, so as to ensure best use of clinical resources.Despite this approach only 26 patients (46%) deemed to be likely cases of autism spectrum disorder received a positive diagnosis.This is not due to overzealous interpretation of ICD-10 diagnostic criteria (which are increasingly recognised as being in urgent need of review), as we tend, if anything, to err in favour of diagnosis, even if ICD-10 (or DSM-IV) criteria, are not strictly fulfilled.Relevant agencies must receive adequate funding for implementing the national autism plan for children. 3This is to benefit not only the children and their families who are struggling with the often devastating impact of this disorder but also the depressingly high number of children whom, we suspect, will be wrongly, or inaccurately, given diagnoses, if assessment services for autism spectrum disorders do not improve.
Infrequent milk consumption plus being overweight may have great risk for asthma in girls
Authors: X.‐M. Mai, A. B. Becker, E. A. C. Sellers, J. J. Liem, A. L. Kozyrskyj
Journal: Allergy (2007)

Background: Inadequate milk consumption and being overweight are each associated with asthma symptoms in children. Milk consumption has been inversely related to childhood overweight. Thus, being overweight may be a pathway or a confounder in milk–asthma relationship. A combination of both factors may be associated with greater risk of asthma than one factor alone. Methods: This study included 246 children with allergist‐diagnosed asthma and 477 nonasthmatic controls at the age of 8–10 years. Information on milk consumption during the last 12 months was obtained from questionnaires. Being overweight was defined as body mass index ≥85th percentile. Being overweight as a possible pathway or confounder was formally tested. The odds ratio (OR) for combined infrequent milk consumption and being overweight in asthmatic vs nonasthmatic children was determined in multivariate logistic regression analyses. Results: There was a significant interaction between milk consumption and sex of the child in relation to asthma. Asthma was significantly associated with infrequent milk consumption in girls (crude OR 2.11, 95% CI 1.05–4.24) but not in boys. The asthma–milk relation in girls was neither mediated by being overweight (p mediation tests = 0.27) nor was the relationship confounded by being overweight (a 9% change in coefficient). Asthmatic girls had 3.6 times increased odds of having combination of infrequent milk consumption and being overweight than nonasthmatic girls (adjusted OR 3.64, 95% CI 1.18–11.24). Asthma was not associated with either factor or with absence of the other in girls. Conclusion: Infrequent milk consumption plus being overweight may have great risk for asthma in girls.
Cation Transport and Structure of the Red-Cell Plasma Membrane
Authors: JOSEPH F. HOFFMAN
Journal: Circulation (1962)

This paper recounts recent work concerning the Na and K permeability of red blood cells. The discussion deals principally with results derived from isolated red-cell membranes, or ghosts. Using defined isolation techniques, a system of ghosts is described in which Na is actively pumped. Like intact cells, the pump requires extracellular K and energy derived from the metabolism. The source of energy for the pump has been assessed by incorporating normally impermeable substrates into the ghost interior at the time of hemolysis. The specific and direct substrate of the pump has been identified as ATP. Further studies are described that correlate the activity of the Na pump with an ATPase. This ATPase, like the pump, requires both Na and K for activity and is inhibited by cardiac glycosides. The evidence points toward the involvement of this ATPase as an intermediate component of the pump reaction.
Resveratrol improves insulin signaling in a tissue-specific manner under insulin-resistant conditions only: in vitro and in vivo experiments in rodents
Authors: Wonyoung Kang, Hyun Ju Hong, Jian Guan, Dong Geon Kim, Eun-Jin Yang, Gwanpyo Koh, Doekbae Park, Chang Hoon Han, Young-Jae Lee, Dae-Ho Lee
Journal: Metabolism (2011)
Brain Scan Findings in Central Nervous System Involvement by Lupus Erythematosus
Authors: DAVID A. BENNAHUM
Journal: Annals of Internal Medicine (1974)

Brain scans were done on 10 women, from 15 to 42 years old, with active systemic lupus erythematosus. Eleven of 12 scans done on the six patients with clinical evidence of active central nervous system disease were abnormal. All eight scans done on the four patients free of neurologic symptoms were normal (chi-square, P < 0.001). Serial studies in three patients, one of whom had three episodes of central nervous system lupus erythematosus during 2 years, showed a close correlation between changes on brain scan and the clinical manifestations of this disease. These data suggest that the brain scan may be a rapid and sensitive tool in the diagnosis of cerebral lupus erythematosus and that studies correlating this test with other markers of lupus cerebritis, such as spinal fluid complement and IgG levels, are called for.
273. Immuno Gene Therapy of Feline Fibrosarcoma Using Intratumoral Magnetofection or Gene-Activated Matrices for Gene Delivery – Preliminary Results of a Veterinary Clinical Study
Authors: Ulrike Schillinger, Bianca Schwarz, Tina Kempf, Anika Jahnke, Cornelia Fischer, Anne Loecher, Stefanie Schlemmer, Johannes Hirschberger, Thomas Brill, Roberto Koestlin, Bernd Gaensbacher, Christian Plank
Journal: Molecular Therapy (2006)

Feline fibrosarcoma is one of the most common feline tumors. It arises spontaneously, is rarely metastatic and relapses within 6 months after standard therapy (surgical resection) in 75 % of the cases. This makes it an ideal model for evaluating immunostimulatory therapeutic strategies. Moreover, besides aggressive surgical excision no effective and versatile treatment is available. Here we report preliminary results from a comparative clinical study where the genes for feline GM-CSF, IFN-g and IL-2 in combination, feline GM-CSF alone or human GM-CSF were administered. The study design is prospective, randomized, placebo- controlled (= standard therapy) and includes five arms: (1) standard therapy, i.e. surgery alone; (2) nonviral Magnetofection of the feline GM-CSF, IFN-g and IL-2 genes into the tumor before surgery or nonviral administration by Magnetofection of feline (3) or human GM-CSF (4) gene alone and (5) nonviral application of the feline GM-CSF, IFN-g and IL-2 genes by a gene-activated-matrix. The procedure included phase I dose finding studies for the gene therapy groups followed by a phase II. Preliminary clinical endpoint is relapse-free survival for one year. Magnetofection, which has been developed in our laboratory, is the association of vectors with magnetic particles (chemicell, Berlin, Germany) and gene delivery under the influence of a magnetic field (Scherer et al. 2002, Gene Ther., Plank et al. 2003, Biol. Chem). It was applied here in order to achieve improved retention of the injected vector dose in the tumor. Copolymer-protected gene vectors (Scherer et al. 2002, J. Gene Med. 4:634-643) were immobilized on a collagen sponge to achieve sustained localized matrix-mediated gene delivery. After tumor excision the gene-activated matrices were implanted in the tumor bed intrasurgically. Pre- and postsurgical diagnosis included complete clinical monitoring of the cats. All gene-therapeutic treatments were well tolerated and led to prolonged relapse-free survival (one year time points: 50 % for intrasurgical implantation of the vector-loaded collagen sponge in the tumor bed, and 52 % for presurgical Magnetofection with human GM-CSF versus 23 % for surgery alone). Additional patients have been admitted to the Magnetofection group such that long-term follow-up will warrant a profound assessment of the benefits of this treatment.
Development of the PSORIQoL, a psoriasis-specific measure of quality of life designed for use in clinical practice and trials
Authors: S.P. McKenna, S.A. Cook, D. Whalley, L.C. Doward, H.L. Richards, C.E.M. Griffiths, D. Van Assche
Journal: British Journal of Dermatology (2003)

Journal Article Development of the PSORIQoL, a psoriasis‐specific measure of quality of life designed for use in clinical practice and trials Get access S.P. McKenna, S.P. McKenna Galen Research, Enterprise House, Lloyd Street North, Manchester M15 6SE, U.K Stephen P.McKenna. E‐mail: smckenna@galen‐research.com Search for other works by this author on: Oxford Academic Google Scholar S.A. Cook, S.A. Cook Galen Research, Enterprise House, Lloyd Street North, Manchester M15 6SE, U.K Search for other works by this author on: Oxford Academic Google Scholar D. Whalley, D. Whalley Galen Research, Enterprise House, Lloyd Street North, Manchester M15 6SE, U.K Search for other works by this author on: Oxford Academic Google Scholar L.C. Doward, L.C. Doward Galen Research, Enterprise House, Lloyd Street North, Manchester M15 6SE, U.K Search for other works by this author on: Oxford Academic Google Scholar H.L. Richards, H.L. Richards Galen Research, Enterprise House, Lloyd Street North, Manchester M15 6SE, U.KThe Dermatology Centre, University of Manchester, Hope Hospital, Manchester M6 8HD, U.K Search for other works by this author on: Oxford Academic Google Scholar C.E.M. Griffiths, C.E.M. Griffiths Galen Research, Enterprise House, Lloyd Street North, Manchester M15 6SE, U.KThe Dermatology Centre, University of Manchester, Hope Hospital, Manchester M6 8HD, U.K Search for other works by this author on: Oxford Academic Google Scholar D. Van Assche D. Van Assche Galen Research, Enterprise House, Lloyd Street North, Manchester M15 6SE, U.KNovartis Pharma AG, Basel, Switzerland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 149, Issue 2, 1 August 2003, Pages 323–331, https://doi.org/10.1046/j.1365-2133.2003.05492.x Published: 01 August 2003 Article history Accepted: 28 March 2003 Published: 01 August 2003
MPs and peers call for greater patient power
Authors: J. Wise
Journal: BMJ (2014)

Patients should have co-ownership of their medical records and not just access to them, a joint report from six all party parliamentary groups has said.1

The report, Patient Empowerment: For Better Quality, More Sustainable Health Services Globally , recommended going beyond NHS England’s current goal of enabling all patients to view their general practice medical records by 2015. The report said that access alone was unlikely to encourage significant …
Accelerated Triglyceride Secretion A METABOLIC CONSEQUENCE OF OBESITY
Authors: R. Paul Robertson, David J. Gavareski, James D. Henderson, Daniel Porte, Edwin L. Bierman
Journal: Journal of Clinical Investigation (1973)

A new animal model was developed to determine the effect of obesity upon endogenous triglyceride secretion. Desert sand rats (Psammomys obesus), rodents which become spontaneously obese and hyperinsulinemic when given ad lib. chow, were given intravenous Triton to allow in vivo measurement of triglyceride secretion rates (TGSR). In a group of 18 fasted animals of varying body weight and degrees of obesity, TGSR correlated significantly with body weight (r=0.68, P < 0.01) indicating that obesity was associated with accelerated endogenous release of triglyceride. In these same animals, basal plasma insulin levels correlated significantly with body weight (r=0.78, P < 0.001) and TGSR correlated significantly with mean plasma insulin levels (r=0.73, P < 0.001), suggesting that hyperinsulinemia may have been the mechanism through which obesity enhanced TGSR. No correlation was found between basal triglyceride level and either body weight, basal insulin, or TGSR which suggested that individual triglyceride removal rates among the animals may have been variable. To test this hypothesis, seven animals were studied prospectively before and after induction of obesity. There were significant increases (P < 0.02) in all parameters, i.e., weight, plasma insulin level, TGSR, and basal triglyceride level. Thus, when each animal was used as its own control, thereby minimizing the postulated factor of variable individual triglyceride removal, increments in basal triglyceride were shown to accompany the development of obesity, hyperinsulinemia, and accelerated triglyceride secretion. These data from studies in the sand rat offer in vivo evidence that obesity leads to accelerated triglyceride secretion, an effect which may be mediated by hyperinsulinemai, and which can be invoked as one possible mechanism to explain hypertriglyceridemia associated with obesity in man.
Pattern of Failure of the Homografted Canine Heart
Authors: SIGMUND A. WESOLOWSKI, JOHN F. FENNESSEY
Journal: Circulation (1953)

A series of puppy hearts was homografted into the necks of adult dogs. The grafts were followed for viability by palpation and by electrocardiograms. Of the grafts studied none functioned longer than one week. Others removed on successive days after transplantation revealed a pattern of failure that suggests that incompatibility to the homografted canine heart is blood-borne.