tbuckley/cabot-search huggingface dataset:
Effect of Tesamorelin on Visceral Fat and Liver Fat in HIV-Infected Patients With Abdominal Fat Accumulation
Authors: Takara L. Stanley, Meghan N. Feldpausch, Jinhee Oh, Karen L. Branch, Hang Lee, Martin Torriani, Steven K. Grinspoon
Journal: JAMA (2014)

<h3>Importance</h3> Among patients infected with human immunodeficiency virus (HIV), visceral adiposity is associated with metabolic dysregulation and ectopic fat accumulation. Tesamorelin, a growth hormone–releasing hormone analog, specifically targets visceral fat reduction but its effects on liver fat are unknown. <h3>Objective</h3> To investigate the effect of tesamorelin on visceral and liver fat. <h3>Design, Setting, and Patients</h3> Double-blind, randomized, placebo-controlled trial conducted among 50 antiretroviral-treated HIV-infected men and women with abdominal fat accumulation at Massachusetts General Hospital in Boston. The first patient was enrolled on January 10, 2011; for the final patient, the 6-month study visit was completed on September 6, 2013. <h3>Interventions</h3> Participants were randomized to receive tesamorelin, 2 mg (n=28), or placebo (n=22), subcutaneously daily for 6 months. <h3>Main Outcomes and Measures</h3> Primary end points were changes in visceral adipose tissue and liver fat. Secondary end points included glucose levels and other metabolic end points. <h3>Results</h3> Forty-eight patients received treatment with study drug. Tesamorelin significantly reduced visceral adipose tissue (mean change, –34 cm<sup>2</sup>[95% CI, –53 to –15 cm<sup>2</sup>] with tesamorelin vs 8 cm<sup>2</sup>[95% CI, –14 to 30 cm<sup>2</sup>] with placebo; treatment effect, –42 cm<sup>2</sup>[95% CI, –71 to –14 cm<sup>2</sup>];<i>P</i> = .005) and liver fat (median change in lipid to water percentage, –2.0% [interquartile range {IQR}, –6.4% to 0.1%] with tesamorelin vs 0.9% [IQR, –0.6% to 3.7%] with placebo;<i>P</i> = .003) over 6 months, for a net treatment effect of –2.9% in lipid to water percentage. Fasting glucose increased in the tesamorelin group at 2 weeks (mean change, 9 mg/dL [95% CI, 5-13 mg/dL] vs 2 mg/dL [95% CI, –3 to 8 mg/dL] in the placebo group; treatment effect, 7 mg/dL [95% CI, 1-14 mg/dL];<i>P</i> = .03), but changes at 6 months in fasting glucose (mean change, 4 mg/dL [95% CI, –2 to 10 mg/dL] with tesamorelin vs 2 mg/dL [95% CI, –4 to 7 mg/dL] with placebo; treatment effect, 2 mg/dL [95% CI, –6 to 10 mg/dL];<i>P</i> = .72 overall across time points) and 2-hour glucose (mean change, –1 mg/dL [95% CI, –18 to 15 mg/dL] vs –8 mg/dL [95% CI, –24 to 8 mg/dL], respectively; treatment effect, 7 mg/dL [95% CI, –16 to 29 mg/dL];<i>P</i> = .53 overall across time points) were not significant. <h3>Conclusions and Relevance</h3> In this preliminary study of HIV-infected patients with abdominal fat accumulation, tesamorelin administered for 6 months was associated with reductions in visceral fat and additionally with modest reductions in liver fat. Further studies are needed to determine the clinical importance and long-term consequences of these findings. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01263717
Abstract 4405: Orthogonal detection of thymidine analogue based cell proliferation and apoptosis using click chemistry combined with antibody based progesterone receptor detection in estradiol treated rat model
Authors: Scott T. Clarke, Arunkumar Arumugam, Rajkumar Lakshmanaswamy
Journal: Cancer Research (2010)

Abstract Detection reagents which can simultaneously measure cell proliferation and apoptosis, or measure chronological changes in cell proliferation over the course of a treatment provide insight into efficacy and mechanisms of treatment on cell cycle and cell heath. Detection reagents which can temporally separate cell proliferation while combined with apoptosis detection provide a powerful new investigative tool. When 5-ethynyl-2′-deoxyuridine (EdU) incorporation is used in conjunction with bromodeoxyuridine (BrdU), cell proliferation measurements are made with orthogonal detection platforms permitting unambiguous identification of proliferation events. In rat mammary epithelial tissue changes in cell proliferation as a result of treatment combined with apoptosis detection demonstrates the value of click chemistry when combined with antibody based detection methods. We use the rat model to show changes in proliferation and apoptosis rates in mammary epithelial tissue, after alteration in hormone treatment. Use of click chemistry labeling in ovariectomized rats shows a decrease in proliferation rate from their basal levels, while estradiol treatment results in an increase in proliferation rate over basal level. Cessation of a 7 day estradiol treatment causes a drop in proliferation rate and an increase in apoptosis which can be efficiently detected using click chemistry. Progesterone receptor levels are measured simultaneously with proliferation rate when click chemistry based detection is combined with antibody based detection methods. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4405.
Drug Extravasation and the Port-a-Cath System
Authors: STEPHEN B. STRUM
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 September 1985Drug Extravasation and the Port-a-Cath SystemSTEPHEN B. STRUM, M.D., JONATHAN E. MCDERMED, Pharm.D.STEPHEN B. STRUM, M.D.Search for more papers by this author, JONATHAN E. MCDERMED, Pharm.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-103-3-472_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In a recent report, Reed and colleagues (1) describe their clinical experience with various subcutaneously implanted catheter systems. In the ten cases described, five had drug extravasation into the skin overlying the access port during overnight infusions. In three cases, resultant tissue injury was severe enough to warrant surgical removal of the vascular access ports.We agree that the potential for drug extravasation with vascular access ports is real. Our experience with the Port-a-Cath (Pharmacia Hospital Products, Piscataway, New Jersey), however, has shown that the occurrence of drug extravasation with this device is not as common as...References1. REEDNEWMANAPPLEFELDSUTTON WKMF. Drug extravasation as a complication of venous access ports. Ann Intern Med. 1985;102:788-9. LinkGoogle Scholar2. STRUMMCDERMEDKORNRAPPAPORTBARNES SJAHK. The PORT-A-CATH (PAC)—a totally implanted catheter system [Abstract]. Proc Am Soc Clin Oncol. 1985;4:263. Google Scholar3. BOTHEPICCIONEAMBROSINOBENOTTILOKICH AWJPJ. Implantable central venous access system. Am J Surg. 1984;147:565-9. CrossrefMedlineGoogle Scholar4. TRACYMCDERMEDSTRUM JJS. Use of an indwelling Huber needle in the PAC. In: The Care and Maintenance of the PORT-A-CATH. Piscataway, New Jersey: Pharmacia Hospital Products, Inc.; 1985:34-6. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Brotman Medical Center Culver City, CA 90230 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByRare complications of vascular access devicesLong-term central venous catheters: Issues for careIntraosseous Infusions: An Important But Forgotten Method of Vascular Access 1 September 1985Volume 103, Issue 3Page: 472-473KeywordsCathetersDrugs Issue Published: 1 September 1985 PDF DownloadLoading ...
Engineering of Tooth-Supporting Structures by Delivery of PDGF Gene Therapy Vectors
Authors: Qiming Jin, Orasa Anusaksathien, Sarah A Webb, Marie A Printz, William V Giannobile
Journal: Molecular Therapy (2004)

Platelet-derived growth factor (PDGF) exerts potent effects on wound healing including the regeneration of tooth-supporting structures. Limitations of topical protein delivery to periodontal osseous defects include transient biological activity and the bioavailability of PDGF at the wound site. The objective of this investigation was to determine the feasibility of in vivo PDGF-B gene transfer to stimulate periodontal tissue regeneration in large tooth-associated alveolar bone defects in rats. Periodontal lesions (0.3 × 0.2 cm in size) were treated with a 2.6% collagen matrix alone or a matrix containing adenoviruses encoding luciferase (control), a dominant negative mutant of PDGF-A (PDGF-1308), or PDGF-B. Block biopsies were harvested at 3, 7, and 14 days post-gene delivery and descriptive histology and histomorphometric analyses were performed. The defects treated with Ad-PDGF-B demonstrated greater proliferating cell nuclear antigen positively stained cells and strong evidence of bone and cementum regeneration beyond that of Ad-luciferase and Ad-PDGF-1308 groups. Quantitative image analysis showed a nearly fourfold increase in bridging bone and sixfold increase in tooth-lining cemental repair in the Ad-PDGF-B-treated sites compared to lesions treated with Ad-luciferase or collagen matrix alone, which showed limited hard tissue neogenesis. In addition, the Xenogen In Vivo Imaging System revealed sustained and localized gene expression of the luciferase reporter at the periodontal lesions for up to 21 days after gene transfer. These results indicate that in vivo direct gene transfer of PDGF-B stimulates alveolar bone and cementum regeneration in large periodontal defects. Gene therapy utilizing PDGF-B may offer the potential for periodontal tissue engineering applications.
THE ENDOCRINE ANGLE
Authors: C. L. Cope
Journal: BMJ (1953)

Sudan is the largest country in Africa, occupying about one million square miles in the north east of the continent (Fig. 1). The country has a long coastline along the Red Sea, and shares boundaries with nine other countries: Egypt in the north and then clockwise with Eritrea, Ethiopia, Kenya, Uganda, Congo, Central African Republic, Chad and Libya. It is so vast in area that there are various climates and numerous rivers, the most famous of which is the Nile which has more than half its length in Sudan with its main tributaries, the Blue and White Niles meeting in Khartoum, the capital city. Sudan is a multiracial, multicultural country with a unique mixture of African and Arab tribes who have lived in harmony over the centuries, though in recent years there have been several civil wars which are principally fuelled by a struggle for power and wealth rather than
Beyond the Tobacco Settlement
Authors: David A. Kessler, Matthew L. Myers
Journal: New England Journal of Medicine (2001)

Under the Master Settlement Agreement signed with the tobacco industry in November 1998, 46 states settled lawsuits in which they sought to recover tobacco-related health care costs and to hold the tobacco companies accountable for decades of wrongdoing. The broad goals of the settlement were to reduce the exposure of young people to tobacco marketing, to generate comprehensive smoking-prevention efforts in every state, and to counteract the effect on children of marketing by the industry. Specifically, the industry agreed to pay the states $206 billion over a 25-year period (four other states settled their lawsuits separately for a total of . . .
Alterations in protein glycosylation in PMA-differentiated U-937 cells exposed to mineral particles.
Authors: N Trabelsi, A Greffard, J C Pairon, J Bignon, G Zanetti, B Fubini, Y Pilatte
Journal: Environmental Health Perspectives (1997)

Carbohydrate moieties of cell glycoconjugates play a pivotal role in molecular recognition phenomena involved in the regulation of most biological systems and the changes observed in cell surface carbohydrates during cell activation or differentiation frequently modulate certain cell functions. Consequently, some aspects of macrophage response to particle exposure might conceivably result from alterations in glycosylation. Therefore, the effect of mineral particles on protein glycosylation was investigated in phorbol myristate acetate (PMA)-differentiated U-937. Jacalin, a lectin specific for O-glycosylated structures, showed a global increase in O-glycosylation in particle-treated cells. In contrast, no significant modifications were observed with concanavalin A, a lectin that recognizes certain N-glycosylated structures. The sialic acid-specific lectins Sambucus nigra agglutinin and Maackia amurensis agglutinin and the galactose-specific lectin Ricinus communis agglutinin revealed a complex pattern of alterations in glycoprotein glycosylation after crystalline silica or manganese dioxide treatments. Expression of sialyl Lewis(x), a glycosylated structure implicated in leukocyte trafficking, could not be detected in control or treated cells. This finding was consistent with the decrease in sialyl Lewis(x) expression observed during PMA-induced differentiation. In conclusion, various treatments used in this study induced quantitative as well as qualitative changes in protein glycosylation. Whether these changes are due to glycosidase release or to an alteration in glycosyltransferase expression remains to be determined. The potential functional implications of these changes are currently under investigation.
Biphasic induction of immediate early gene expression accompanies activity-dependent angiogenesis and myofiber remodeling of rabbit skeletal muscle.
Authors: J B Michel, G A Ordway, J A Richardson, R S Williams
Journal: Journal of Clinical Investigation (1994)

Sustained contractile activity of skeletal muscle promotes angiogenesis, as well as transformation of contractile protein isoforms and mitochondrial proliferation within myofibers. Since the products of immediate early genes such as c-fos, c-jun, and egr-1 function in many signaling pathways governing cellular responses to external stimuli, we sought to determine whether sustained contractile activity induces their expression in skeletal muscle. Low voltage electrical stimulation was applied to the motor nerve innervating rabbit tibialis anterior muscles for periods ranging from 45 min to 21 d. Northern and Western analysis demonstrated marked but transient inductions of c-fos, c-jun, and egr-1 mRNA and protein within the first 24 h. Longer durations of stimulation were associated with a secondary and sustained rise in the abundance of c-fos, c-jun, and p88egr-1 protein that, surprisingly, was not accompanied by detectable changes in mRNA. Immunohistochemistry demonstrated c-fos immunoreactivity within myofiber and vascular cell nuclei during both early and late phases of this response. These findings reveal a complex pattern of c-fos, c-jun, and egr-1 expression in response to nerve stimulation and suggest that these proteins could function in regulatory pathways that modify muscle phenotype.
Le Veen vs. Denver peritoneovenous shunts: Inadequate numbers or technique?
Authors: Laurence M. Blendis, Robert H. Lund
Journal: Hepatology (1987)

Peritoneovenous shunts (PVSs) have provided salutary effects on medically recalcitrant ascites, functional renal impairment, nutritional derangements, ventilatory embarrassment, and locomotion potential in patients with cirrhosis. While the LeVeen (LPVS) and Denver (DPVS) PVSs are most frequently implanted in such patients, postoperative complications of bleeding gastroesophageal varices, sepsis, and shunt occlusion occur with notable frequency. Addressing primarily the complication of PVS occlusion, a randomized prospective trial of LPVSs and DPVSs was conducted in cirrhotic patients with refractory ascites. From July 1, 1982 to July 1, 1984, 26 initial PVSs were implanted for hepatic-related intractable ascites. Twenty-two patients were eligible for randomization (cirrhosis, sterile ascites, initial PVS, total bilirubin level ≦6.0 mg/dL, prothrombin time ≦5-s prolongation, serum creatinine level ≦2.0 mg/dL [creatinine clearance rate ≧20 mL/min], absence of recent [<30 days] bleeding gastroesophageal varices, or absent spontaneous encephalopathy). Twelve LPVSs and ten DPVSs were implanted; however, one patient with a DPVS was found to have hepatic polycystic disease and was excluded from analysis. All patients were followed up until death or January 1, 1985. The PVS patency determinations included contrast shuntography, technetium Tc 99m albumin scintigraphy, sequential manual compression (DPVS), and operative or autopsy observation. Using the Kaplan-Meier actuarial analysis, the LPVS patency proved to be highly superior to that of the DPVS, while survival was not significantly different. As LPVS and DPVS complications other than patency are comparable, the LPVS is preferred for its superior patency in cirrhotic patients with intractable ascites.
Stimulus properties of inhaled substances.
Authors: R W Wood
Journal: Environmental Health Perspectives (1978)

Inhaled substances can modify behavior by their toxic action, or because they are discriminable events, or because they can support or suppress behavior. They can be used as discriminative stimuli at concentrations above the olfactory threshold. Inhalants can elicit unconditioned reflexes. As aversive stimuli, they can be studied in respondent conditioning experiments (e.g. conditioned suppression), in punishment paradigms, or as negative reinforcers in escape paradigms. Inhalants can also be positive reinforcers; their intoxicating properties have engendered patterns of chronic self-administration (solvent abuse). Such stimulus properties should be considered in industrial hygiene and environmental quality decisions. Laboratory techniques to study such properties abound.
Physicians' group seeks nuclear arms ban
Authors: Mark S. Litwin
Journal: JAMA (1985)

The history and recent activities of the International Physicians for the Prevention of Nuclear War (IPPNW) are reported. Founded in 1980 by cardiologists Bernard Lown of the United States and Eugene Chazov of the Soviet Union, the group has attracted well over 100,000 members from 51 countries. Following the organization's fifth congress in Budapest in June 1985, a four-city tour of the United States by three American and four Soviet physicians was co-sponsored by IPPNW, Physicians for Social Responsibility, and the Soviet Committee of Physicians for the Prevention of Nuclear War. Through separate lecture series aimed at physicians and laypersons, the doctors sought to persuade colleagues to take an active stand against nuclear war, and to increase public awareness of the medical realities of a nuclear attack. A similar tour of the Soviet Union is planned.
Paroxysmal Atrial Tachycardia with Atrioventricular Block
Authors: LEONARD M. GOLDBERG, J. DAVID BRISTOW, BRENT M. PARKER, LEONARD W. RITZMANN
Journal: Circulation (1960)

Paroxysmal atrial tachycardia with block is a cardiac arrhythmia that is usually a manifestation of digitalis toxicity in patients with serious heart disease. The arrhythmia generally ends promptly after potassium administration and withdrawal of digitalis. Since the ventricular rates may be slow and regular, the arrhythmia may be difficult to recognize clinically. Atrial rates as slow as 115 per minute may be seen in cases which are otherwise typical of the condition. In our series associated pulmonary disease was present in 54 per cent and cor pulmonale in 27 per cent of the cases.
A NEW MASTOID RETRACTOR.
Authors: FRANK ALLPORT
Journal: JAMA (1897)

For some years I have been using my old retractors in mastoid and similar operations, and have been well pleased with them. The only objection noticed has been the fact that, as the incision and bone opening has been growing larger, owing to our improved knowledge and operations, the retractor has at times seemed to me rather small. This difficulty has been obviated by myself and others by using two retractors, one in each extremity of the wound, being careful they do not overlap each other. This arrangement has proven eminently satisfactory, opening as it does a large and bloodless field of operation, and I still feel that in its thorough usefulness it is as good a method as can be adopted. Some operators, however, dislike to use two retractors; others have repeatedly expressed the opinion that the blades of the retractors should be always parallel to each other, both
Mutual Antagonism between the Ebola Virus VP35 Protein and the RIG-I Activator PACT Determines Infection Outcome
Authors: Priya Luthra, Parameshwaran Ramanan, Chad E. Mire, Carla Weisend, Yoshimi Tsuda, Benjamin Yen, Gai Liu, Daisy W. Leung, Thomas W. Geisbert, Hideki Ebihara, Gaya K. Amarasinghe, Christopher F. Basler
Journal: Cell Host & Microbe (2013)
Malignant Hyperthermia— A Misnomer
Authors: Elemér K. Zsigmond
Journal: JAMA (1980)

<h3>To the Editor.—</h3> During the past 15 years, I have been involved in the screening of relatives of patients with malignant hyperthermia, and, therefore, I became increasingly aware of the inappropriateness of the term "malignant hyperthermia." Hence, I proposed a new, more descriptive term that, rather, is based on the pathological findings: acute familial peranesthetic rhabdomyolysis. This classification conveys the pathoetiologic signs and the treatment aspects to all physicians at once. Further arguments in favor of this term are as follows: (1) The word "malignant" is often misconstrued by the patients and affected relatives as meaning a carcinomatous tumor. As a result, many potential carriers of this anomaly declined evaluation of their genetic defect. Furthermore, insurance policies were turned down as a result. (2) Before the occurrence of this name for the syndrome, the mortality was indeed high, justifying the term "malignant." But now the survival rate has been greatly
Effect of Alpha-Methyl DOPA in Severe and Malignant Hypertension
Authors: Paul J. Cannon
Journal: JAMA (1962)

A new approach to the control of arterial hypertension involving the administration of a methylated derivative of the naturally-occurring amino-acid dihydroxyphenylalanine (DOPA) has been studied in 33 patients. Alpha-methyl DOPA given orally was found to be a potent, and, in general, a smooth and well-tolerated hypotensive agent for treatment of severe and malignant hypertension. The agent seemed to have less adverse effect on renal function than other hypotensive agents. Also, the compound had no specific effect on sodium balance or aldosterone secretion. The data indicate that the compound does not interfere with endogenous norepinephrine synthesis as was thought at first. It has been suggested that alpha-methyl DOPA interferes with the activity or tissue release of norepinephrine. These results have interesting theoretical and practical implications in hypertensive vascular disease.