tbuckley/cabot-search huggingface dataset:
Growth of the aortic anastomosis, annulus, and root after the arterial switch procedure performed in infancy.
Authors: M Hourihan, S D Colan, G Wernovsky, U Maheswari, J E Mayer, S P Sanders
Journal: Circulation (1993)

BACKGROUND We investigated the size and growth potential of the neoaortic root and aortic anastomosis after the arterial switch operation (ASO) for D-transposition of the great arteries (D-TGA) performed in infants. Circumferential suture lines connecting the great arteries and extensive surgery on the arterial roots to transplant the coronary arteries are essential parts of the ASO. However, little is known about the growth of the aortic anastomosis, the neoaortic root, and the neoaortic annulus after the ASO performed in infancy. METHODS AND RESULTS Serial echocardiograms on 50 patients with D-TGA who underwent ASO in infancy at our institution were reviewed, and the size of the aortic anastomosis, the neoaortic root, and the neoaortic annulus were compared with similar structures in a group of 312 control subjects. Before surgery, the native pulmonary root (future neoaortic root) was 1.59 SD larger (P &lt; .001) and the native pulmonary annulus (future neoaortic annulus) was 1.4 SD larger (P &lt; .001) in infants with D-TGA than the aortic root and annulus of control patients. At a mean of 22 months (12 months to 6 1/2 years) after surgery, the diameter of the aorta at the anastomosis was 0.45 SD smaller than the ascending aorta of control subjects (P &lt; .001). The neoaortic root was 2.9 SD larger (P &lt; .001) and the neoaortic annulus was 1.6 SD larger (P &lt; .001) than the comparable structures in the control population. Most important, growth of the aortic anastomosis was commensurate with somatic growth, but the dilation of the neoaortic root appeared to be progressive over time. The neoaortic root was significantly more dilated in patients with a history of pulmonary artery banding (P &lt; .001) and in patients with neoaortic regurgitation (P &lt; .001). The presence of a ventricular septal defect was not significantly related to postoperative neoaortic root size. CONCLUSIONS This study underlies the importance of continued acquisition and examination of the data regarding the long-term outcome of the arterial switch operation performed in infancy.
The role of cAMP- and cGMP-dependent protein kinases in the cardiac actions of the new calcium sensitizer, levosimendan
Authors: H Haikala
Journal: Cardiovascular Research (1997)

The role of phosphodiesterase III inhibition and calcium sensitization in the cardiac actions of levosimendan, (R)-[[4-(1,4,5, 6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propane dinitrile, was studied.Various heart preparations were used to investigate positive inotropy, chromotropy, coronary flow and calcium sensitivity of contractile proteins. The cAMP- and cGMP-dependent protein kinases (PKA and PKG) were inhibited by KT5720 and KT5823, respectively. Furthermore, the synthesis of cAMP was stimulated by forskolin and increased phosphorylation of troponin I was induced by isoprenaline.In Langendorff guinea-pig heart, levosimendan (0.01-1 microM) and milrinone (0.1-10 microM) increased the left ventricular systolic peak pressure almost to the same extent. In the presence of KT5720 (1 microM) milrinone was devoid of positive inotropic activity. In contrast, KT5720 did not antagonize the inotropic effect of levosimendan at < or = 0.03 microM (-up to the EC50 of levosimendan). The effects of levosimendan and milrinone on heart rate and coronary flow were not affected by KT5720. The PKG inhibitor, KT5823 (1 microM), on the other hand, potentiated the levosimendan-induced increase in coronary flow while it had no effect on the increase induced by milrinone. The mechanical parameters were not affected by KT5823. In the papillary muscle, the positive inotropic effect of milrinone but not that of levosimendan was potentiated by forskolin (0.1 microM). In contrast to milrinone, the positive inotropy by levosimendan was decreased by isoprenaline pretreatment (0.1 microM; 3 min). In line with this, the calcium-sensitizing effect of levosimendan was decreased in skinned fibers prepared from isoprenaline-treated hearts.Our results indicate that the cardiac effects of levosimendan at its therapeutically relevant concentrations were not mediated through PKA or PKG and its positive inotropy is therefore most probably due to the previously reported troponin-C-mediated calcium sensitization of contractile proteins.
Repair mechanisms in embryos: wound healing and learning from how embryos repair perfectly
Authors: P. Martin
Journal: European Respiratory Journal (2003)

Embryos heal wounds very rapidly and efficiently without leaving a scar. Studying how they do this can tell a great deal about the natural morphogenetic movements of embryogenesis as well as suggesting ways in which adult tissues could repair more efficiently. Using live confocal imaging of transgenic Drosophila embryos expressing green fluorescent protein­labelled actin in epithelial tissues, the key actin machineries that drive the paradigm morphogenetic process of dorsal closure, which appear to bear striking analogy with re­epithelialisation of a vertebrate skin wound have been revealed. Using embryos expressing mutant forms of the various small guanadine triphosphatases, the function of each of these actin­based elements, the actin cable and dynamic filopodia and lamellipodia, were tested in both dorsal closure and the repair of laser­generated wound holes in the fly embryo. These experiments conducted in embryonic chicks and mice and in the neonatal PU.1 null mouse, which is genetically macrophageless, suggest that an inflammatory response is not essential for healing and may indeed be causal of fibrosis in postembryonic animals. Consequently, a microarray approach was used with this mouse in order to identify a portfolio of candidate inflammation/fibrosis genes. Finally, by taking advantage of the translucency of the zebrafish larval tail, the author9s group has begun to make differential interference contrast movies of the inflammatory response and to dissect the genetics of this process by screening for mutants that fail to recruit leukocytes to the wound site and by morpholino knockdown of candidate “inflammation” genes. The hope is that these basic cell and molecular studies in genetically tractable organisms will supply the clues needed to design the new repair and regeneration medicines of the future.
Synaptic Currents Generated by Neuronal Acetylcholine Receptors Sensitive to α-Bungarotoxin
Authors: Zhong-wei Zhang, Jay S Coggan, Darwin K Berg
Journal: Neuron (1996)

Nicotinic acetylcholine receptors are widely distributed throughout the nervous system, but their functions remain largely unknown. One of the most abundant is a class of receptors that contains the α7 gene product, has a high relative permeability to calcium, and binds α-bungarotoxin. Here, we report that receptors sensitive to α-bungarotoxin, though concentrated in perisynaptic clusters on neurons, can generate a large amount of the synaptic current. Residual currents through other nicotinic receptors are sufficient to elicit action potentials, but with slower rise times. This demonstrates a postsynaptic response for α-bungarotoxin-sensitive receptors on neurons and suggests that the functional domain of the postsynaptic membrane is broader than previously recognized.
Massive Intrathecal Overdose: “Check the Label Twice!”
Authors: David G. Poplack
Journal: New England Journal of Medicine (1984)

First developed for the treatment of childhood leukemia, intrathecal chemotherapy has been used with increasing frequency to treat many cancers of adulthood in which spread to the meninges occurs. Intrathecal administration provides an effective means of achieving therapeutic concentrations of selected anticancer agents in cerebrospinal fluid, because this route bypasses the blood–brain barrier, which normally restricts the central-nervous-system penetration of most systemically administered drugs.1 Intrathecal chemotherapy is almost always administered by the intralumbar route. After intrathecal injection of a drug, the initial volume of distribution is relatively small (approximately 140 ml for cerebrospinal fluid vs. approximately 5000 ml for blood); . . .
New proposals for reorganisation of healthcare staff in England
Authors: J. Dixon
Journal: BMJ (2011)

Extensive, rapid, and risky



Last year’s white paper Equity and Excellence: Liberating the NHS proposed extensive reform of the NHS.1 Away from the current parliamentary debates on the resulting Health and Social Care Bill, the Department of Health is still seeking responses to proposals in some key areas. One of these is how the healthcare workforce might be developed in the future⇑.2

The workforce is central to the current NHS—1.4 million people are employed in 300 roles and cost more than 60% of the £107bn (€123bn; $174bn) NHS budget. How intelligently the supply of staff, their education, training, and development are planned and managed is crucial for the future viability of the NHS. Previous experience suggests substantial room for improvement. The Health Select Committee in 2007 noted the shortage of skills and data on which to plan supply, lack of coordination in planning across professional silos, poor engagement from local NHS organisations for whom these matters were a secondary consideration, lack of integration with financial planning and plans for future service development, and the lack of a long term view.3

The new proposals cover both planning the supply of and the education, training, and future development of healthcare staff in England, except for public health staff (for which there will be a separate consultation). The rationale for change includes the points made by the select committee, but also that planning has been too “top-down,” siloed by profession, inflexible, and not driven enough by local employers. It argues that this has resulted …
Inclusive Conjunctivitis With Hearing Loss
Authors: J.A. Gow
Journal: JAMA (1974)

<h3>To the Editor.—</h3> Inclusion conjunctivitis is an acute follicular conjunctivitis caused by a member of the<i>Chlamydia (Bedsonia)</i>group of microorganisms. The agent is transmitted sexually, and the eye infection is usually accompanied by genitourinary symptoms. In both experimentally and naturally acquired infections, otitis media has been reported.<sup>1,2</sup>In the case described here, severe hearing loss accompanied the ocular symptoms. <h3>Report of a Case.—</h3> The patient, a 39-year-old white woman, was seen with irritation, redness, and secretion in the right eye of two months' duration, and of similar involvement of the left eye of one month's duration. She had been treated with a number of tropical antibacterial agents (including sulfacetamide drops and a mixture of polymyxin B sulfate, neomycin sulfate, and bacitracin zinc [Neosporin Ointment]), and with both topical and systemic antiinflammatory agents. She had also noticed a marked impairment of her hearing, and a diagnosis of bilateral otitis
Cerebral perfusion in invasive meningococcal disease
Authors: Peter J Flegg
Journal: BMJ (2008)

Vitamin D deficiency is widespread in Scotland I agree with Holick 1 and Sievenpiper et al 2 about the urgent need to highlight the neglected subject of vitamin D deficiency in the United Kingdom.We have found in our general practice in Edinburgh a (to us) surprisingly high prevalence of gross vitamin D deficiency.The deficiency affects not only our South Asian patients but also a considerable number of those with white skin colour.Between 2005 and 2007, blood samples were taken from 99 patients aged 15-85.We included patients suspected of having a possible vitamin D deficiency: patients of South Asian origin or other ethnic minorities, patients with vague musculoskeletal symptoms or overweight, patients taking antiepileptic drugs, patients using sunscreen or make up, housebound patients, and patients with little exposure to sunlight.The figure shows our as yet unpublished results.According to the definitions of most vitamin D researchers, insufficient vitamin D concentrations are those below 75 nmol/l.In our sample only 2% had a sufficient vitamin D concentration.Measurements below 25 nmol/l are defined as severe deficiency; in our sample, the proportion was 47%.We select the letters for these pages from the rapid responses posted on bmj.com favouring those received within five days of publication of the article to which they refer.Letters are thus an early selection of rapid responses on a particular topic.
Comparative Exercise-Cardiorespiratory Performance of Normal Men in the Third, Fourth, and Fifth Decades of Life
Authors: JOHN S. HANSON, BURTON S. TABAKIN, ARTHUR M. LEVY, DAVID B. HILL
Journal: Circulation (1968)

The circulatory and respiratory responses to five levels of treadmill exercise were recorded for 75 normal males divided equally in the age groups 20 to 29, 30 to 39, and 40 to 49 years. Parameters studied included heart rate, cardiac output, stroke volume, intra-arterial blood pressure, minute ventilatory volume, oxygen uptake, and carbon dioxide elimination. Values for peripheral vascular resistance, left ventricular work, and stroke work indices were calculated. Intergroup and intragroup differences were analyzed by modified covariance technique using oxygen uptake per square meter of body surface area as the concomitant variable reflecting a specific midrange work level. Significant differences were observed between groups in cardiac output, stroke volume, systolic, diastolic, and mean arterial blood pressure as well as pressure-related variables with regard to absolute values and trend over the exercise spectrum. The results indicate that normal untrained males in the fourth and fifth decades of life react to moderate and heavy upright exercise with statistically significant systemic pressure elevations as compared to 20-year-olds. A tendency toward initially high cardiac output and stroke volume during light exercise was observed in the older men. Relatively small subsequent increments in cardiac output with resultant low absolute values during heavier work were also characteristic for this group as reflected in their decreasing stroke output at submaximal loads.
The Overdiagnosis of Lyme Disease
Authors: Craig P. Cleveland
Journal: JAMA (1993)

<h3>To the Editor.</h3> —I was dismayed to read that Steere et al<sup>1</sup>ignored many of the basic principles of the practice of medicine as well as of good research. First, they ignored the accepted guidelines as published by the National Institutes of Health<sup>2</sup>that Lyme disease is a clinical diagnosis. Their insistence on eliminating cases that had not resulted in positive Lyme disease tests ignores this fact. Second, Luger and Krauss<sup>3</sup>showed that the interlaboratory variation seen in their studies reinforced the concept that the diagnosis of Lyme disease must be made on a clinical basis. The inconsistencies were again shown by Bakken et al<sup>4</sup>when they reviewed 45 laboratories. Why do Steere et al believe that their tests are better than any others? Is it in order to promote their own hypotheses? Third, since there does not exist a test to demonstrate a "cure" in
Diagnosis of ascending aortic dissection by transesophageal echocardiography: Utility of M-mode in recognizing artifacts
Authors: Arturo Evangelista, Herminio Garcia-del-Castillo, Teresa Gonzalez-Alujas, Rosa Dominguez-Oronoz, Armando Salas, Gaieta Permanyer-Miralda, Jordi Soler-Soler
Journal: Journal of the American College of Cardiology (1996)
1012 Consensus interferon and ribavirin retreatment of chronic HCV patients with non-response or relapse after previous alpha-interferon therapy
Authors: W BOECHER, M SPRINZL, J MUDTER, H HILLENBRAND, H BROCKMANN, P GALLE, H LOEHR
Journal: Hepatology (2003)

We investigated the in vivo effects of orally administered cariprazine (RGH-188; trans-N-{4-[2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl]-cyclohexyl}-N′,N′-dimethyl-urea), a D3/D2 dopamine receptor partial agonist with ∼10-fold preference for the D3 receptor. Oral bioavailability of cariprazine at a dose of 1 mg/kg in rats was 52% with peak plasma concentrations of 91 ng/mL. Cariprazine 10 mg/kg had good blood–brain barrier penetration, with a brain/plasma AUC ratio of 7.6:1. In rats, cariprazine showed dose-dependent in vivo displacement of [3H](+)-PHNO, a dopamine D3 receptor-preferring radiotracer, in the D3 receptor-rich region of cerebellar lobules 9 and 10. Its potent inhibition of apomorphine-induced climbing in mice (ED50 = 0.27 mg/kg) was sustained for 8 h. Cariprazine blocked amphetamine-induced hyperactivity (ED50 = 0.12 mg/kg) and conditioned avoidance response (CAR) (ED50 = 0.84 mg/kg) in rats, and inhibited the locomotor-stimulating effects of the noncompetitive NMDA antagonists MK-801 (ED50 = 0.049 mg/kg) and phencyclidine (ED50 = 0.09 mg/kg) in mice and rats, respectively. It reduced novelty-induced motor activity of mice (ED50 = 0.11 mg/kg) and rats (ED50 = 0.18 mg/kg) with a maximal effect of 70% in both species. Cariprazine produced no catalepsy in rats at up to 100-fold dose of its CAR inhibitory ED50 value. Cariprazine 0.02–0.08 mg/kg significantly improved the learning performance of scopolamine-treated rats in a water-labyrinth learning paradigm. Though risperidone, olanzapine, and aripiprazole showed antipsychotic-like activity in many of these assays, they were less active against phencyclidine and more cataleptogenic than cariprazine, and had no significant effect in the learning task. The distinct in vivo profile of cariprazine may be due to its higher affinity and in vivo binding to D3 receptors versus currently marketed typical and atypical antipsychotics.
Postperfusion Ventilation Studies in the Diagnosis of Pulmonary Embolism An Economic Appraisal
Authors: L ALDEN PARKER, JORDAN B. RENNER, LAWRENCE M. VINCENT, WILLIAM H. McCARTNEY
Journal: Clinical Nuclear Medicine (1987)

Postperfusion lung ventilation imaging with xenon-127 (Xe-127) gas was evaluated from an economic perspective. Results of five years experience at a tertiary referral center suggest that the use of postperfusion lung ventilation techniques can significantly reduce patient costs for diagnostic studies and may reduce institutional costs for radiopharmaceuticals.
Where shall John go? North-western Australia.
Authors: C L Hughes
Journal: BMJ (1977)

<h3>Introduction</h3> Achieving optimal placement of the left ventricular (LV) lead in cardiac resynchronisation therapy (CRT) is a prerequisite in order to achieve maximum clinical benefit, and is likely to help avoid non-response. Pacing outside scar tissue and targeting late activated segments may improve outcome. The present study will be the first randomised controlled trial to compare the efficacy of <i>real-time</i> image-guided LV lead delivery to conventional CRT implantation. In addition, to estimate the cost-effectiveness of targeted lead implantation, an early decision analytic model was developed, and described here. <h3>Methods and analysis</h3> A multicentre, interventional, randomised, controlled trial will be conducted in a total of 130 patients with a class I or IIa indication for CRT implantation. Patients will be stratified to ischaemic heart failure aetiology and 1:1 randomised to either empirical lead placement or live image-guided lead placement. Ultimate lead location and echocardiographic assessment will be performed by core laboratories, blinded to treatment allocation and patient information. Late gadolinium enhancement cardiac magnetic resonance imaging (CMR) and CINE-CMR with feature-tracking postprocessing software will be used to semi-automatically determine myocardial scar and late mechanical activation. The subsequent treatment file with optimal LV-lead positions will be fused with the fluoroscopy, resulting in live target-visualisation during the procedure. The primary endpoint is the difference in percentage of successfully targeted LV-lead location. Secondary endpoints are relative percentage reduction in indexed LV end-systolic volume, a hierarchical clinical endpoint, and quality of life. The early analytic model was developed using a Markov-model, consisting of seven mutually exclusive health states. <h3>Ethics and dissemination</h3> The protocol was approved by the Medical Research Ethics Committee Utrecht (NL73416.041.20). All participants are required to provide written informed consent. Results will be submitted to peer-reviewed journals. <h3>Trial registration number</h3> NCT05053568; Trial NL8666.
Folate for oral contraceptive users may reduce cervical cancer risk
Authors: William A. Check
Journal: JAMA (1980)

Folic acid supplementation may help reduce the risk of cervical cancer in women taking combination oral contraceptive agents. According to data presented at the American Society for Clinical Nutrition meeting in Washington, DC, by Charles E. Butterworth, MD, chief, Division of Nutrition, University of Alabama School of Medicine, Birmingham, young women with mild to moderate cervical dysplasia had significant improvement in this condition after taking 10 mg of folate orally each day for three months. At present there is no epidemiologic evidence that oral contraceptive agents increase the risk of cervical cancer in the population as a whole. But many investigators believe that cervical dysplasia progresses to carcinoma in situ of the cervix in some women, and there is preliminary evidence suggesting that oral contraceptive agents can hasten this progression. The effect of folate on abnormal cervical cytology has been investigated over the last five years by Butterworth, obstetrician-gynecologist Kenneth
Cytochrome b Phylogeny and the Taxonomy of Great Apes and Mammals
Authors: Jose Castresana
Journal: Molecular Biology and Evolution (2001)

In the Linnaean system of classification, the generic status of a species is part of its binomial name, and it is therefore important that the classification at the level of genus is consistent at least in related groups of organisms. Using maximum-likelihood phylogenetic trees constructed from a large number of complete or nearly complete mammalian cytochrome b sequences, I show that the distributions of intrageneric and intergeneric distances derived from these trees are clearly separated, which allows the limits for a more rational generic classification of mammals to be established. The analysis of genetic distances among hominids in this context provides strong support for the inclusion of humans and chimpanzees in the same genus. It is also of interest to decipher the main reasons for the possible biases in the mammalian classification. I found by correlation analysis that the classification of mammals of large body size tends to be oversplit, whereas that of small mammals has an excess of lumping, which may be a manifestation of the larger difficulty in finding diagnostic characters in the classification of small animals. In addition, and contrary to some previous observations, there is no correlation between body size and rate of cytochrome b evolution in mammals, which excludes the difference in evolutionary rates as the cause of the observed body size taxonomic bias.