tbuckley/cabot-search huggingface dataset:
Long-term Retinal Function and Structure Rescue Using Capsid Mutant AAV8 Vector in the rd10 Mouse, a Model of Recessive Retinitis Pigmentosa
Authors: Ji-jing Pang, Xufeng Dai, Shannon E Boye, Ilaria Barone, Sanford L Boye, Song Mao, Drew Everhart, Astra Dinculescu, Li Liu, Yumiko Umino, Bo Lei, Bo Chang, Robert Barlow, Enrica Strettoi, William W Hauswirth
Journal: Molecular Therapy (2010)

The retinal degeneration 10 (rd10) mouse is a well-characterized model of autosomal recessive retinitis pigmentosa (RP), which carries a spontaneous mutation in the β subunit of rod cGMP-phosphodiesterase (PDEβ). Rd10 mouse exhibits photoreceptor dysfunction and rapid rod photoreceptor degeneration followed by cone degeneration and remodeling of the inner retina. Here, we evaluate whether gene replacement using the fast-acting tyrosine-capsid mutant AAV8 (Y733F) can provide long-term therapy in this model. AAV8 (Y733F)-smCBA-PDEβ was subretinally delivered to postnatal day 14 (P14) rd10 mice in one eye only. Six months after injection, spectral domain optical coherence tomography (SD-OCT), electroretinogram (ERG), optomotor behavior tests, and immunohistochemistry showed that AAV8 (Y733F)-mediated PDEβ expression restored retinal function and visual behavior and preserved retinal structure in treated rd10 eyes for at least 6 months. This is the first demonstration of long-term phenotypic rescue by gene therapy in an animal model of PDEβ-RP. It is also the first example of tyrosine-capsid mutant AAV8 (Y733F)-mediated correction of a retinal phenotype. These results lay the groundwork for the development of PDEβ-RP gene therapy trial and suggest that tyrosine-capsid mutant AAV vectors may be effective for treating other rapidly degenerating models of retinal degeneration. The retinal degeneration 10 (rd10) mouse is a well-characterized model of autosomal recessive retinitis pigmentosa (RP), which carries a spontaneous mutation in the β subunit of rod cGMP-phosphodiesterase (PDEβ). Rd10 mouse exhibits photoreceptor dysfunction and rapid rod photoreceptor degeneration followed by cone degeneration and remodeling of the inner retina. Here, we evaluate whether gene replacement using the fast-acting tyrosine-capsid mutant AAV8 (Y733F) can provide long-term therapy in this model. AAV8 (Y733F)-smCBA-PDEβ was subretinally delivered to postnatal day 14 (P14) rd10 mice in one eye only. Six months after injection, spectral domain optical coherence tomography (SD-OCT), electroretinogram (ERG), optomotor behavior tests, and immunohistochemistry showed that AAV8 (Y733F)-mediated PDEβ expression restored retinal function and visual behavior and preserved retinal structure in treated rd10 eyes for at least 6 months. This is the first demonstration of long-term phenotypic rescue by gene therapy in an animal model of PDEβ-RP. It is also the first example of tyrosine-capsid mutant AAV8 (Y733F)-mediated correction of a retinal phenotype. These results lay the groundwork for the development of PDEβ-RP gene therapy trial and suggest that tyrosine-capsid mutant AAV vectors may be effective for treating other rapidly degenerating models of retinal degeneration.
Sudden Death in Infancy: A Study of Cardiac Specialized Tissue
Authors: R. H. Anderson, J. Bouton, C. T. Burrow, A. Smith
Journal: BMJ (1974)

The hearts from 15 cot death patients have been compared with those of 15 controls. In one of the cot death patients an accessory atrioventricular connexion known to be capable of producing ventricular pre-excitation and sudden death was identified. In all hearts examined additional segments of specialized tissue were found in relation to the atrioventricular orifices which may have been significant in producing pre-excitation. Haemorrhagic lesions were present in the atrial myocardium and conducting tissues of hearts from both groups, but no evidence was found of cellular degeneration in the atrioventricular bundle. There is a need for further studies of conducting tissues in sudden death syndromes.
Giant inguinal and suprapubic mastocytomas in an adult with a history of childhood mastocytosis
Authors: V. Menéndez, J.A. Galán, Y. Delgado, P. Devesa, A. Teruel, M. Pérez
Journal: British Journal of Dermatology (2001)

Sir, We describe a 29‐year‐old patient with systemic mastocytosis who developed inguinopubic lesions. The pathological analysis was of mastocytoma. A 29‐year‐old man, with cutaneous mastocytosis diagnosed in childhood and confirmed by various cutaneous biopsies, presented with three hard papillomatous verrucous lesions (Fig. 1a) arising from the suprapubic area and encroaching on the base of the penis and the inguinal fold. The largest lesion measured approximately 7 × 6 cm, had grown slowly but progressively over the previous 5 years from a brownish flat plaque, and was lighter in colour than the surrounding skin. The normal skin showed oval reddish urticarial papules and plaques, except for the palms of the hands, the soles of the feet, and flexures (Fig. 1b). The patient denied any sexual activity and was taking no medication. Full blood count, blood film, coagulation tests and blood chemistry were within normal limits except for IgM (392 mg dL−1, normal 53–334) and C‐reactive protein (18·5 mg L−1, normal 0–12). Urine chemistry showed elevations of dopamine (448 µg in 24 h, normal 65–400) and vanillylmandelic acid (14·6 mg in 24 h, normal < 9). Excision of the smallest lesion was done under local anaesthetic. When the incision was made, rapid hardening of the skin occurred with severe diffuse bleeding. Histological analysis showed epidermal acanthosis and papillomatosis, and a dense nodular infiltrate in the dermis made up of mast cells with ovoid nuclei, slightly granular cytoplasm, and metachromasia as demonstrated with toluidine blue staining (Fig. 1c). The second lesion was removed under spinal anaesthesia and the histological findings were the same. As the patient had been unsupervised for several years, further examination was carried out, after removal of the lesions, in order to determine any systemic involvement. A combination of osteopenic, lytic and sclerotic changes was seen in the left humerus and left costal arch, suggesting systemic mastocytosis. A bone scan with 99mTc‐dimethylphosphonate confirmed these changes. Biopsy of the bone marrow confirmed the presence of infiltration by mature mastocytes.
Mark Walport will be next UK government chief scientific adviser, cabinet office announces
Authors: S. Mayor
Journal: BMJ (2012)

Mark Walport, director of the Wellcome Trust, has been appointed to take over as the UK government chief scientific adviser next year, the cabinet office has announced.

Walport will take over from the current chief scientist John Beddington in April 2013. The chief scientific adviser’s role is to advise the prime minister and UK government on scientific and technology matters to inform policy and decision making.

Their input is particularly obvious at times of crisis, including the Icelandic ash cloud in 2010, the swine flu epidemic in 2009, and the foot and mouth outbreaks of 2001 and 2007, but applies across all areas …
TRENDS AND PREDICTORS OF SMOKING CESSATION AFTER PERCUTANEOUS CORONARY INTERVENTION: EXPERIENCE FROM OLMSTED COUNTY, MINNESOTA, 1999-2010
Authors: Ondrej Sochor, Ryan J. Lennon, John Bresnahan, Ivana Croghan, Quinn Pack, Juan P. Rodriguez Escudero, Tomas Kara, Virend Somers, Francisco Lopez-Jimenez, Randal Thomas
Journal: Journal of the American College of Cardiology (2012)
Asymptomatic Cytomegalovirus Mononucleosis
Authors: WILLIAM BYRON HERLONG
Journal: Annals of Internal Medicine (1973)

Comments and Corrections1 November 1973Asymptomatic Cytomegalovirus MononucleosisWILLIAM BYRON HERLONG, M.D., RICHARD H. ESHAM, M.D.WILLIAM BYRON HERLONG, M.D.Search for more papers by this author, RICHARD H. ESHAM, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-79-5-756_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We read with great interest the article by Jordan and associates (Ann Intern Med 79:153-160, 1973) concerning spontaneous cytomegalovirus mononucleosis. The usual clinical course is that of a mild febrile illness without prominent splenomegaly or lymphadenopathy; however, a more severe illness with prominent splenomegaly and lymphadenopathy may occur, and, as Jordan emphasizes, these clinical findings should not lead the clinician to exclude the diagnosis. We report here an unusual presentation of spontaneous cytomegalovirus mononucleosis in an asymptomatic individual with prominent lymphadenopathy and splenomegaly.Patient D.C. is a 15-year-old white boy who was seen 6 July 1973 with... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Moncrief Army Hospital Fort Jackson, South Carolina PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByMyocarditis complicating cytomegalovirus mononucleosis 1 November 1973Volume 79, Issue 5Page: 756-756KeywordsSplenomegaly Issue Published: 1 November 1973 PDF DownloadLoading ...
The lean and slippered pantaloon
Authors: P. A Gardiner
Journal: BMJ (1994)

Shakespeare's portrait of geriatric existence—sans eyes, sans teeth, sans megabytes, sans many other essential needs for publication in a modern Elizabethan age—would, I suppose, challenge him as it challenges me in this account—sans statistics, sans references, and sans acronyms.

In the context of medical, media, and environmental warnings, which distress us all, I offer some encouragement about survival.

Without question, I owe my life to the medical and nursing help that I have always been given. It now seems that my lifestyle so much disgusts the medical establishment and increases managers' costs that I am on a hit list. But, despite conventional, fashionable, scientific, and statistical norms, I survive. Why?

Father and grandfather died at 77—both from cardiac failure after prolonged treatment with digitalis. One a heavy smoker, the other a non-smoker. Mother, a heavy smoker, died by her own hand at 62. One aunt died of lung cancer at 63 (a non-smoker) and her sister at 90 after a stroke (a non-smoker). One sister died at 75 from cancer (a heavy smoker). One sister alive at 72 (a non-smoker), and one brother died at 21 from lobar pneumonia (a casual smoker). Maternal grandfather (a pipe smoker) died of tuberculosis at 59 and grandmother died from hypertension and heart failure at 79 (a non-smoker). I see no evidence of …
In Vivo Activation of Midbrain Dopamine Neurons via Sensitized, High-Affinity α6∗ Nicotinic Acetylcholine Receptors
Authors: Ryan M. Drenan, Sharon R. Grady, Paul Whiteaker, Tristan McClure-Begley, Sheri McKinney, Julie M. Miwa, Sujata Bupp, Nathaniel Heintz, J. Michael McIntosh, Merouane Bencherif, Michael J. Marks, Henry A. Lester
Journal: Neuron (2008)
Burns rehabilitation is more than skin deep
Authors: Monique Berger, Stephen Wilson
Journal: BMJ (2004)

Cholesterol values seem to divergeEditor-The targets for cholesterol management seem to be ever decreasing, but I cannot get my head around the fact that in the new guidelines from the British Hypertension Society box 8 suggests we should consider treatment if the 10 year risk of cardiovascular disease is > 20% and the total cholesterol level is > 3.5 mmol/l but the target to be attained, which is printed beside box 8, is higher, 4 mmol/l. 1 Can someone explain this anomaly to a simple general practitioner who will have to explain it to patients?
Intravitreal Aflibercept Injection for Neovascular Age-related Macular Degeneration
Authors: Ursula Schmidt-Erfurth, Peter K. Kaiser, Jean-François Korobelnik, David M. Brown, Victor Chong, Quan Dong Nguyen, Allen C. Ho, Yuichiro Ogura, Christian Simader, Glenn J. Jaffe, Jason S. Slakter, George D. Yancopoulos, Neil Stahl, Robert Vitti, Alyson J. Berliner, Yuhwen Soo, Majid Anderesi, Olaf Sowade, Oliver Zeitz, Christiane Norenberg, Rupert Sandbrink, Jeffrey S. Heier
Journal: Ophthalmology (2013)
Treatment of Breast Cancer with Medroxyprogesterone.
Authors: Franco M. Muggia
Journal: Annals of Internal Medicine (1967)

s1 May 1967Treatment of Breast Cancer with Medroxyprogesterone.Franco M. Muggia, M.D., Peter A. Cassileth, M.D., Frederick A. Flatow, M.D., Alfred A. Gellhorn, M.D., F.A.C.P., George A. Hyman, M.D., F.A.C.P., Manuel Ochoa Jr., M.D.Franco M. Muggia, M.D.Search for more papers by this author, Peter A. Cassileth, M.D.Search for more papers by this author, Frederick A. Flatow, M.D.Search for more papers by this author, Alfred A. Gellhorn, M.D., F.A.C.P.Search for more papers by this author, George A. Hyman, M.D., F.A.C.P.Search for more papers by this author, Manuel Ochoa Jr., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-66-5-1066_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe observation that progestational agents alone or combined with estrogens might be useful in the management of cancer led to the treatment of 36 patients (34 women and 2 men) with disseminated breast cancer with medroxyprogesterone acetate (Provera®). Patients were selected from two groups: In one, relapse had occurred after treatment with ablative surgery or conventional hormonal and chemotherapeutic agents; in the other, primary estrogen therapy was limited by intolerance or cardiovascular disease. Provera (100 mg) was administered intramuscularly three times weekly or by mouth daily for at least 5 weeks.Of the 27 patients receiving adequate treatment, 7 had... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Franco M. Muggia, M.D.; Peter A. Cassileth, M.D.; Frederick A. Flatow, M.D.; Alfred A. Gellhorn, M.D., F.A.C.P.; George A. Hyman, M.D., F.A.C.P.; Manuel OchoaJr., M.D.Affiliations: New York, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHomologous ELISA for measurement of medroxyprogesterone acetate in serumProtection by Progestagens or Antioestrogens 1 May 1967Volume 66, Issue 5Page: 1066-1066KeywordsBreast cancerCancer treatmentCardiovascular diseasesCardiovascular therapyChemotherapeutic agentsEstrogensMouthPatientsSurgery ePublished: 1 December 2008 Issue Published: 1 May 1967 PDF downloadLoading ...
Low-Level Human Equivalent Gestational Lead Exposure Produces Sex-Specific Motor and Coordination Abnormalities and Late-Onset Obesity in Year-Old Mice
Authors: J. Leigh Leasure, Anand Giddabasappa, Shawntay Chaney, Jerry E. Johnson, Konstantinos Pothakos, Yuen Sum Lau, Donald A. Fox
Journal: Environmental Health Perspectives (2007)

Low-level developmental lead exposure is linked to cognitive and neurological disorders in children. However, the long-term effects of gestational lead exposure (GLE) have received little attention.Our goals were to establish a murine model of human equivalent GLE and to determine dose-response effects on body weight, motor functions, and dopamine neurochemistry in year-old offspring.We exposed female C57BL/6 mice to water containing 0, 27 (low), 55 (moderate), or 109 ppm (high) of lead from 2 weeks prior to mating, throughout gestation, and until postnatal day 10 (PN10). Maternal and litter measures, blood lead concentrations ([BPb]), and body weights were obtained throughout the experiment. Locomotor behavior in the absence and presence of amphetamine, running wheel activity, rotarod test, and dopamine utilization were examined in year-old mice.Peak [BPb] were < 1, < or = 10, 24-27, and 33-42 microg/dL in control, low-, moderate- and high-dose GLE groups at PN0-10, respectively. Year-old male but not female GLE mice exhibited late-onset obesity. Similarly, we observed male-specific decreased spontaneous motor activity, increased amphetamine-induced motor activity, and decreased rotarod performance in year-old GLE mice. Levels of dopamine and its major metabolite were altered in year-old male mice, although only forebrain utilization increased. GLE-induced alterations were consistently larger in low-dose GLE mice.Our novel results show that GLE produced permanent male-specific deficits. The nonmonotonic dose-dependent responses showed that low-level GLE produced the most adverse effects. These data reinforce the idea that lifetime measures of dose-response toxicant exposure should be a component of the neurotoxic risk assessment process.
Chlorpromazine‐induced lupus anticoagulant and associated immunologic abnormalities
Authors: Rosa T. Canoso, Herbert S. Sise
Journal: American Journal of Hematology (1982)

Abstract Chronic administration of chlorpromazine is associated with the development of a lupus‐like circulating anticoagulant and a variety of immunological abnormalities. The prevalence of these findings was studied in 123 psychiatric patients. The anticoagulant was present in 11 of 30 patients receiving chlorpromazine (CPZ), in none of 17 patients who had been off phenothiazine therapy for over a year and in none of 53 controls. It was also seen in 5 of 13 patients who had been switched from CPZ to another phenothiazine even after several years being off CPZ. The anticoagulant was characterized by prolongation of the partial thromboplastin time, thromboplastin dilution test, and Russell's viper venom time. Washed frozen platelets partially corrected the abnormality induced by the anticoagulant. In all but one case the anticoagulant was associated with positive antinuclear antibody test and/or increased serum IgM. Six of 16 patients also had decreased complement levels, and two had a positive direct Coombs' test. None of these patients manifested bleeding, hemolysis, splenomegaly, or other clinical features of systemic lupus erythematosus.
GW25-e0731 The Triage of Coronary Artery Occlusion and its Long-term Prognosis-A Propensity-Matched Study
Authors: Gai Jingjing, Zhai Xue, Zhang Kaiyi, Jin Qinhua, Sun Zhijun, Chen Yundai, Chen Lian, Liu Hongbin, Gai Luyue
Journal: Journal of the American College of Cardiology (2014)
DNA Cross-Links in Human Tumor Cells Exposed to the Prodrug PR-104A: Relationships to Hypoxia, Bioreductive Metabolism, and Cytotoxicity
Authors: Rachelle S. Singleton, Christopher P. Guise, Dianne M. Ferry, Susan M. Pullen, Mary J. Dorie, J. Martin Brown, Adam V. Patterson, William R. Wilson
Journal: Cancer Research (2009)

PR-104, currently in clinical trial, is converted systemically to the dinitrobenzamide nitrogen mustard prodrug PR-104A, which is reduced selectively in hypoxic cells to cytotoxic hydroxylamine (PR-104H) and amine (PR-104M) metabolites. Here, we evaluate the roles of this reductive metabolism, and DNA interstrand cross-links (ICL), in the hypoxic and aerobic cytotoxicity of PR-104. Using a panel of 9 human tumor cell lines, cytotoxicity was determined by clonogenic assay after a 2-hour aerobic or hypoxic exposure to PR-104A. PR-104H and PR-104M were determined by high performance liquid chromatography/mass spectrometry, and ICL with the alkaline comet assay. Under hypoxia, the relationship between ICL and cell killing was similar between cell lines. Under aerobic conditions, there was a similar relationship between ICL and cytotoxicity, except in lines with very low rates of aerobic reduction of PR-104A (A2780, C33A, H1299), which showed an ICL-independent mechanism of PR-104A cytotoxicity. Despite this, in xenografts from the same lines, the frequency of PR-104-induced ICL correlated with clonogenic cell killing (r(2) = 0.747) with greatest activity in the fast aerobic metabolizers. In addition, changing levels of hypoxia in SiHa tumors modified both ICL frequency and tumor growth delay in parallel. We conclude that both aerobic and hypoxic nitroreduction of PR-104A contribute to the monotherapy antitumor activity of PR-104 in human tumor xenografts, and that ICL are responsible for its antitumor activity and represent a broadly applicable biomarker for tumor cell killing by this novel prodrug.
Remarks ON THE DIAGNOSIS OF ACUTE ABDOMINAL CRISES
Authors: A. H. Burgess
Journal: BMJ (1920)

IN tlhese two lectures I propose to discuss the diagnosis of acute abdominal crises in a general sense, and to consider first of all, individually, the various symptoms and signs met with in suclh crises, attributing to eaclh its relative value as a factor in diagnosis, and as an indication for treatment; and secondly, these same symptoms arranged in groups, such as are observed clinically in the different types of abdominal crises.First, then, let us consider the diagnostic value of such symptoms as may be present in an acute abdominal crisis. GENERAL SYMPTOMS,.The general symptoms include:1. Various degrees of shock or collapse.2. Alterations in the frequency and character of-the pulse..3. Changes in the temperature. 4. Alterations in the type of respiration-" thoracic" type. 5. Other symptoms, such as a dry and furred condition of the tongue, hiccough, strangury, and tenesmus.Speaking generally, one may say tlhat, although these general symptoms are useful in directing attention to the possibility of a crisis having occurred, yet thev give no clue to its nature, nor are they alone of much value as in- dications for treatment.They may occur alike in serious and comparatively trivial abdominal lesions, as evidenced, on tle.one band, by the profound degrees of shock which may accompany a simple contusion of the abdominal wall, or be present during an attack of colic; while, on the other hand, cases of perforation of a viscus are sometimes seen with practically no rise of temperature or pulse, and with very little, if any, shock.In' fact, so unlikely is -it that any material assistance will be obtained from a consideration of the temperature or pulse that I feel strongly that fewer cases would pass unrecognized in their early stages were it to become tlhe universal rule never to take the temperature nor count tlle pulse in a suspected abdominal crisis; they are only too likely to mislead.The per- sistence of shock and of the other general symptoms is of far greater diagnostic importance than is their initial degree.LOCAL SYMPTOMS.t is, then, mainly upon the local symptoms and signs, -those referable to the abdomen itelf2-'thatwel have' to: rely in deciding -questions of diagnosis and 'treatmkent In any acute abdominal crisis.These include:1. Abdominal pain.2. Cutaneous hyperalgesia (" viscero-8ensory reflex) 3. Tenderness, local and general.4. Nausea, vomiting. 5. Muscular rigidity (" viscero-motor" reflex).6. Abdominal distension. 7. Presence of free gas in the peritoneal cavity.8. Presence of free fluid in the peritoneal cavity. - 9. Local abdominal or pelvic swelli'ng.. 10.Certain changes ascertainable upon rectal examination.
TCT-72 Impact of Gender on Adverse Cardiovascular Events Following Percutaneous Coronary Intervention: Pooled Analysis from the SPIRIT II, III and IV trials
Authors: Usman Baber, Roxana Mehran, Annapoorna Kini, Kleanthis Theodoropoulos, Nilusha Gukathasan, Gregg Stone
Journal: Journal of the American College of Cardiology (2012)