tbuckley/cabot-search huggingface dataset:
Increased liver uptake of liposomes and improved targeting efficacy by labeling with asialofetuin in rodents
Authors: Jian Wu, Pei Liu, Jian-Liang Zhu, Sivaramaiah Maddukuri, Mark A. Zern
Journal: Hepatology (1998)

To improve liposome-directed therapy of liver disease and gene delivery, it would be beneficial to selectively target hepatocytes. For this purpose, conventional liposomes (CL) were labeled with asialofetuin (AF), an asialoglycoprotein. The biodistribution of AF-labeled liposomes (AF-L) in mice and their incorporation into rat hepatocytes, and their potential use in acute liver injury, were investigated. AF-L displayed a quicker plasma clearance than CL, and 25.4%, 2.7%, and 1.2% of the injected dose remained in the plasma versus 47.0%, 26.1%, and 9.5% of CL, respectively at 2, 4, and 20 hours after the injection. Total liver uptake of AF-L (73% ± 3.9%) was markedly higher ( P &lt; .005) than CL (16.5% ± 1.8%) 4 hours after the injection. Liposomal radioactivity (cpm/mg) was greatly enhanced in the liver (11-fold) during the first 4 hours after the administration of 14 C-AF-L, and was much higher than in 14 C-CL-injected mice (1.5-fold). In vitro ncubation of isolated rat hepatocytes with 14 C-AF-L or intravenous injection of 14 C-AF-L in rats resulted in higher hepatocyte-bound radioactivity compared with 14 C-CL ( P &lt; .01-.005). AF-L-associated 1,1′-dilinoleyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) fluorescent signals were not only located in Kupffer cells, but also in hepatocytes, in which bile canaliculus networks were imaged. Intravenous administration of vitamin E (VE)-associated CL (VE-CL, 1 mg/mouse) significantly lowered alanine transaminase (ALT) levels in CCl 4 -treated mice (196 ± 79 vs. 2,107 ± 235 U/mL; P &lt; .01). The ALT level in CCl 4 + VE-AF-L group was decreased to 38 ± 16 units/mL, which was significantly lower than the CCl 4 + VE-CL group ( P &lt; .05). In conclusion, labeling liposomes with AF led to a shortened liposome plasma half-life and greatly enhanced uptake of AF-L liposome by the liver. The enhanced uptake resulted from an increased incorporation of hepatocytes with AF-L liposomes. VE-associated AF liposomes further improved the protective effect of VE liposomes on CCl 4 -induced acute liver injury in mice. Preferential hepatocyte incorporation of AF-L liposomes suggests a useful hepatocyte-targeting approach for drug delivery and gene transfection.
The Medical Appropriateness of Tympanostomy Tubes Proposed for Children Younger Than 16 Years in the United States
Authors: Lawrence C. Kleinman
Journal: JAMA (1994)

<h3>Objective.</h3> —To describe the clinical reasons tympanostomy tubes are proposed for children and to assess their appropriateness. <h3>Design.</h3> —Analysis of data previously collected prospectively by a national utilization review (UR) firm during a two-step UR process to assess the medical appropriateness of tympanostomy tube placement. Nurses interviewed otolaryngologists' and primary care physicians' office staff to collect clinical data. For a randomly selected subsample of cases found inappropriate, we reviewed subsequent interviews of the otolaryngologists by physician reviewers, who looked for possible extenuating clinical circumstances or additional clinical data that might have changed the appropriateness category. <h3>Setting.</h3> —Otolaryngologists' practices from 49 states and the District of Columbia. <h3>Patients.</h3> —All 6611 children younger than 16 years who were insured by three clients of the UR firm and whose proposal to receive tympanostomy tubes was reviewed by this system from January 1,1990, through July 31,1991. The insurance companies in the study insured 5.6 million Americans at the time of the study. <h3>Main Outcome Measure.</h3> —The medical appropriateness of tympanostomy tube surgery according to explicit criteria developed by an expert panel using the RAND/University of California—Los Angeles modified Delphi method. <h3>Results.</h3> —A total of 6429 (97%) of the cases were proposed for recurrent acute otitis media, otitis media with effusion, or both. Making generous clinical assumptions, 41% of the proposals for these reasons had appropriate indications, 32% had equivocal indications, and 27% had inappropriate ones. Considering the additional information available from the subsample review, the proportion appropriate was 42%, equivocal 35%, and inappropriate 23%. <h3>Conclusion.</h3> —About one quarter of tympanostomy tube insertions for children in this study were proposed for inappropriate indications and another third for equivocal ones. (<i>JAMA</i>. 1994;271:1250-1255)
Pressure on hospitals has led to worse care for older patients
Authors: N. Hawkes
Journal: BMJ (2012)

Acute care in hospitals cannot be sustained in its present form, the Royal College of Physicians has warned in a new report.1 An ageing population with multiple and complex needs is producing greater demands, but these have to be met by a hospital system that has a third fewer beds than there were 25 years ago. 

Emergency admissions have risen by 37% in the past decade, the report says. While hospitals have so far dealt with this rise by reducing patients’ length of stay, this cannot be sustained indefinitely. Lengths of stay have stopped declining and in the past three years have started to rise among patients aged over 85.

Patients are increasingly frail, with 65% aged over 65, and an increasing proportion have dementia. But hospitals, services, and staff are ill suited to dealing with patients who have these complex needs.

Within hospitals, continuity of care …
Procainamide, Quinidine, and Lupus Erythematosus
Authors: PETER AMADIO
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 March 1985Procainamide, Quinidine, and Lupus ErythematosusPETER AMADIO JR., M.D., DOYLE M. CUMMINGS, Pharm.D., LARRY DASHOWPETER AMADIO JR., M.D.Search for more papers by this author, DOYLE M. CUMMINGS, Pharm.D.Search for more papers by this author, LARRY DASHOWSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-102-3-419_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: A recent article by West and colleagues (1) described quinidine-induced lupus erythematosus. We report the cases of two patients who developed a lupus-like syndrome while receiving procainamide (Procan SR; Parke-Davis, Morris Plains, New Jersey). The syndrome resolved clinically on discontinuation of the drug but later recurred on quinidine therapy.A 78-year-old white woman with a history of degenerative joint disease and arteriosclerotic cardiovascular disease developed chest pain and had trigeminy on electrocardiography. The patient was hospitalized and the arrhythmia was controlled with procainamide therapy. The patient was discharged on a regimen of propranolol, 40 mg every 12...Reference1. WESTMCMAHONPORTANOVA SMJ. Quinidine-induced lupus erythematosus. Ann Intern Med. 1984;100:840-2. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Jefferson Medical College of Thomas Jefferson University Philadelphia, PA 19107 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByInterpretando a biópsia de pele e importância da imunofluorescência para as doenças reumáticas autoimunesQuinidineDrug-Induced DiseaseAdverse immunological effects of drugs other than anticance drugs and drugs used in immunologyANTIDYSRHYTHMIC DRUGSQuinidineDRUG AND ENVIRONMENTAL LUPUS: CLINICAL MANIFESTATIONS AND DIFFERENCESQuinine induced lupus-like syndrome and cardiolipin antibodies.Quinidine-induced rheumatic syndromesDRUG-INDUCED LUPUSOther Connective Tissue Disorders and The Use of GlucocorticoidsDrug-related lupus syndromes and their relationship to spontaneously occurring systemic lupus erythematosusDrug-Induced Rheumatic SyndromesAssociation of Antibody to Histone Complex H2A–H2B with Symptomatic Procainamide-Induced LupusSouthwestern Internal Medicine Conference: Molecular Mechanisms of AutoimmunityDrug-Related LupusTwo Distinct Quinidine-Induced Rheumatic SyndromesMICHAEL G. COHEN, M.B.B.S., SUMANT KEVAT, M.B.B.S., MICHAEL V. PROWSE, M.B.B.S., MICHAEL J. AHERN, M.B.B.S.Cardiac glycosides and drugs used in dysrhythmiasDrug-induced lupus 1 March 1985Volume 102, Issue 3Page: 419-419KeywordsArrhythmiaCardiovascular diseasesDegenerative joint diseaseDrug therapyElectrocardiographyIschemiaLupus erythematosus Issue Published: 1 March 1985 PDF DownloadLoading ...
Mutation of <i>SDHB</i> is a Cause of Hypoxia-Related High-Altitude Paraganglioma
Authors: Nidia Y. Cerecer-Gil, Luis E. Figuera, Francisco J. Llamas, Mauricio Lara, José G. Escamilla, Ruben Ramos, Gerardo Estrada, A. Karim Hussain, José Gaal, Esther Korpershoek, Ronald R. de Krijger, Winand N.M. Dinjens, Peter Devilee, Jean Pierre Bayley
Journal: Clinical Cancer Research (2010)

Paragangliomas of the head and neck are neuroendocrine tumors and are associated with germ line mutations of the tricarboxylic acid cycle-related genes SDHB, SDHC, SDHD, and SDHAF2. Hypoxia is important in most solid tumors, and was directly implicated in tumorigenesis over 40 years ago when it was shown that dwelling at high altitudes increases the incidence of carotid body hyperplasia and paragangliomas. Although recent research has now elucidated several pathways of hypoxia in paragangliomas, nothing is currently known of the genetics or of gene-environment interactions in high-altitude paraganglioma. We postulated that SDH mutations might play a role in these tumors.Patients from a Mexican family, originating and resident in Guadalajara, were tested for mutations of SDHD, and subsequently, for mutations of SDHB followed by immunohistochemical confirmation of SDHB loss.Two patients, born and resident at altitudes of between 1,560 and 2,240 m, were found to have head and neck paragangliomas, including a remarkably aggressive recurrent tumor. Mutation analysis identified a pathogenic missense mutation in exon 7 of SDHB, c.689G>A, p.Arg230His, and loss of the SDHB protein was confirmed by immunohistochemistry.This is the first report of a SDH gene mutation in paraganglioma at high altitude. A rapidly recurrent head and neck paraganglioma is a very rare finding in an SDH mutation carrier, suggesting a gene-environment interaction. Neither patient showed evidence of sympathetic paraganglioma.
Osteopontin is expressed and functional in human eosinophils
Authors: I. Puxeddu, N. Berkman, D. Ribatti, R. Bader, H. M. Haitchi, D. E. Davies, P. H. Howarth, F. Levi‐Schaffer
Journal: Allergy (2009)

Eosinophils are critically involved in allergic inflammation and tissue remodeling. Osteopontin (OPN) is a glycoprotein molecule which exhibits pro-fibrogenic and pro-angiogenic properties and has recently also been implicated in allergic diseases. In this study, we investigated the expression and function of OPN in human eosinophils.Osteopontin mRNA (RT-PCR) and protein (immunofluorescence) expression in peripheral blood eosinophils from atopic human subjects were evaluated. Soluble OPN release was determined in resting and activated eosinophils. The contribution of OPN to eosinophil-induced angiogenesis was determined using the chick embryo chorio- allantoic membrane (CAM) assay and OPN-induced eosinophil chemotaxis was determined (ChemoTx System microplate wells). Finally, OPN expression in bronchoalveolar lavage (BAL) fluids from mild asthmatic and normal control subjects was determined.Osteopontin is expressed in human eosinophils and is increased following GM-CSF and IL-5 activation. Eosinophil-derived OPN contributes to eosinophil-induced angiogenesis. Recombinant OPN promotes eosinophil chemotaxis in vitro and this effect is mediated by alpha(4)beta(1) integrin binding. Soluble OPN is increased in the bronchoalveolar lavage fluid from mild asthmatic subjects and correlates with eosinophil counts.We therefore conclude that OPN is likely to contribute to the process of angiogenesis observed in the airways in asthma.
A FEW PERSONAL RECOLLECTIONS OF HELMHOLTZ.
Authors: HERMANN KNAPP
Journal: JAMA (1902)

The writer had the great privilege of being a pupil of Helmholtz, living eight years next door to him, at Heidelberg, seeing him almost every day. It gives me great pleasure to furnish some personal notes about Helmholtz's character, his working methods, industry, etc. His working methods, from my first interview with him, aroused my admiration, by their directness. I presented myself in his laboratory without any introduction. He asked me what I wanted to do. I said I wanted to study ophthalmology, and my particular object was to drill myself in physiological optics, under assistance I could not obtain in Berlin. "Where do you wish to begin your work?" I said: "I would like to begin at a certain problem in your paper on accommodation, of which I can not find a solution." He replied: "Sit down and let us see." I showed him the place, and told him
Myocardial Protection. The Pathophysiology of Reperfusion and Reperfusion Injury.
Authors: H M PIPER
Journal: Cardiovascular Research (1993)

Myocardial Protection. The Pathophysiology of Reperfusion and Reperfusion Injury. H M PIPER H M PIPER Düsseldorf, Germany Eds D M Yellon and R B Jennings. (Pp 214; $124.) New York: Raven Press, 1992. ISBN 0-88167-865-1. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 1, January 1993, Pages 142–143, https://doi.org/10.1093/cvr/27.1.142a Published: 01 January 1993
A Genetic Variation in Inositol Polyphosphate 4 Phosphatase A Enhances Susceptibility to Asthma
Authors: Mamta Sharma, Jyotsna Batra, Ulaganathan Mabalirajan, Shilpy Sharma, Rana Nagarkatti, Jyotirmoi Aich, Surendra K. Sharma, Pramod V. Niphadkar, Balaram Ghosh
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Microarray data from mouse studies have identified a number of genes to be differentially expressed in allergen-sensitized mice lungs.Objectives: Taking leads from these datasets, we attempted to identify novel genes associated with atopic asthma in humans.Methods: We performed family-based genetic association analysis on selected markers within or in proximity of 21 human homologs of genes short-listed from ovalbumin-sensitized mouse studies in the Gene Expression Omnibus database of the National Center for Biotechnology Information. Family-based and case-control studies were undertaken for fine mapping and functional variation analysis of INPP4A (inositol polyphosphate 4 phosphatase type I). Western blot analysis was performed to analyze INPP4A protein stability from human platelets.Measurements and Main Results: Our genetic association studies of 21 human genes in 171 trios led to the identification of a biallelic repeat (rs3217304) in INPP4A, associated with atopic asthma (P = 0.009). Further studies using additional three single nucleotide polymorphisms (SNPs), +92031A/T, +92344C/T, and +131237C/T, and two microsatellite markers, D2S2311 and D2S2187, revealed significant genetic associations with loci +92031A/T (P = 0.0012) and +92344C/T (P = 0.004). A nonsynonymous SNP, +110832A/G (Thr/Ala), present within a sequence enriched with proline, glutamic acid, serine, and threonine (PEST), in proximity of these two loci, showed a significant association with atopic asthma (P = 0.0006). The association results were also replicated in an independent cohort of 288 patients and 293 control subjects (P = 0.004). PEST score and Western blot analyses indicated a functional role of this SNP in regulating INPP4A protein stability.Conclusions: In our study, INPP4A was identified as a novel asthma candidate gene, whereby the +110832A/G (Thr/Ala) variant affected its stability and was significantly associated with asthma.
Improving quality of mother-infant relationship and infant attachment in socioeconomically deprived community in South Africa: randomised controlled trial
Authors: P. J Cooper, M. Tomlinson, L. Swartz, M. Landman, C. Molteno, A. Stein, K. McPherson, L. Murray
Journal: BMJ (2009)

To assess the efficacy of an intervention designed to improve the mother-infant relationship and security of infant attachment in a South African peri-urban settlement with marked adverse socioeconomic circumstances.Randomised controlled trial.Khayelitsha, a peri-urban settlement in South Africa.449 pregnant women.The intervention was delivered from late pregnancy and for six months postpartum. Women were visited in their homes by previously untrained lay community workers who provided support and guidance in parenting. The purpose of the intervention was to promote sensitive and responsive parenting and secure infant attachment to the mother. Women in the control group received no therapeutic input from the research team.quality of mother-infant interactions at six and 12 months postpartum; infant attachment security at 18 months. Secondary outcome: maternal depression at six and 12 months.The intervention was associated with significant benefit to the mother-infant relationship. At both six and 12 months, compared with control mothers, mothers in the intervention group were significantly more sensitive (6 months: mean difference=0.77 (SD 0.37), t=2.10, P<0.05, d=0.24; 12 months: mean difference=0.42 (0.18), t=-2.04 , P<0.05, d=0.26) and less intrusive (6 months: mean difference=0.68 (0.36), t=2.28, P<0.05, d=0.26; 12 months: mean difference=-1.76 (0.86), t=2.28 , P<0.05, d=0.24) in their interactions with their infants. The intervention was also associated with a higher rate of secure infant attachments at 18 months (116/156 (74%) v 102/162 (63%); Wald=4.74, odds ratio=1.70, P<0.05). Although the prevalence of maternal depressive disorder was not significantly reduced, the intervention had a benefit in terms of maternal depressed mood at six months (z=2.05, P=0.04) on the Edinburgh postnatal depression scale).The intervention, delivered by local lay women, had a significant positive impact on the quality of the mother-infant relationship and on security of infant attachment, factors known to predict favourable child development. If these effects persist, and if they are replicated, this intervention holds considerable promise for use in the developing world.Current Controlled Trials ISRCTN25664149.
The reasonable workup before recommending medical or surgical therapy: an overall strategy.
Authors: G C Friesinger
Journal: Circulation (1982)

The workup of a patient with chronic ischemic heart disease (IHD) before the selection of medical-surgical or medical therapy depends on multiple objective and subjective factors. These include symptoms, extent of anatomic disease (degree of coronary arteriosclerosis and left ventricular abnormalities), objective evidence of ischemia, extent of left ventricular dysfunction, and recent intercurrent ischemic events. In a minority of patients, a single factor is of overwhelming importance; e.g., the presence of severe left main coronary artery narrowing in a symptomatic patient indicates surgery is a better choice, whereas evidence of advanced left ventricular dysfunction suggests that surgery is likely to be risky and of limited help to the patient. In most instances, multiple factors should be considered before making a recommendation. The patient should be placed in the appropriate clinical subset and the objective factors that are most important in determining survival should be evaluated. Hence, an exercise electrocardiographic study to evaluate symptoms and exercise tolerance in a patient with angina pectoris and radioventriculographic studies with exercise to estimate left ventricular performance in a patient who complains of fatigue and breathlessness are superior to the subjective interpretations of routine clinical examinations. Asymptomatic patients and those with excellent exercise tolerance pose the most difficult decisions. Perhaps serial (even annual) noninvasive evaluation is appropriate in such patients in light of the current uncertainty about how to manage them. Laboratory tests should be used selectively, systematically and sequentially. The high cost of many of the examinations is reason to avoid duplication. When noninvasive evaluation can answer the question being posed and the cost of hospitalization avoided, this should be done. However, there is little reason to perform noninvasive examinations that do not answer the clinical question being asked; hence, in many patients it is appropriate to proceed directly to coronary arteriography rather than to perform a variety of "screening" examinations before this procedure.
Amino-Glutethimide and Metastatic Adrenal Cancer
Authors: David E. Schteingart
Journal: JAMA (1966)

Several compounds have been reported to effectively inhibit hormone production and neoplastic growth in patients with Cushing's syndrome due to metastatic adrenocortical carcinoma.<sup>1</sup>The most effective of these compounds has been orthopara-prime DDD (<i>o, p'</i>, DDD), but the severe side effects which are often encountered has limited its usefulness, particularly for long-term therapy. We have observed a most dramatic and symptomless suppression, of six months' duration, of the excessive cortisol secretion of a patient with metastatic adrenocortical carcinoma. This was brought about by daily administration of a newly discovered inhibitor of steroidal biosynthesis, amino-glutethimide (Elipten, formerly marketed as an anticonvulsive agent). This report details these observations and compares the clinical and biochemical responses in the same patient of<i>o, p'</i>, DDD and amino-glutethimide. <h3>Methods</h3> Urinary 17-hydroxycorticosteroids (170HCS) were determined by the method of Porter and Silber<sup>2</sup>; urinary 17-ketosteroids (17KS) by the method of Drekter<sup>3</sup>; plasma 170HCS by
A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model
Authors: Takehisa Kitazawa, Tomoyuki Igawa, Zenjiro Sampei, Atsushi Muto, Tetsuo Kojima, Tetsuhiro Soeda, Kazutaka Yoshihashi, Yukiko Okuyama-Nishida, Hiroyuki Saito, Hiroyuki Tsunoda, Tsukasa Suzuki, Hideki Adachi, Taro Miyazaki, Shinya Ishii, Mika Kamata-Sakurai, Takeo Iida, Aya Harada, Keiko Esaki, Miho Funaki, Chifumi Moriyama, Eriko Tanaka, Yasufumi Kikuchi, Tetsuya Wakabayashi, Manabu Wada, Masaaki Goto, Takeshi Toyoda, Atsunori Ueyama, Sachiyo Suzuki, Kenta Haraya, Tatsuhiko Tachibana, Yoshiki Kawabe, Midori Shima, Akira Yoshioka, Kunihiro Hattori
Journal: Nature Medicine (2012)