tbuckley/cabot-search huggingface dataset:
Adenoidectomy and Adenotonsillectomy for Recurrent Acute Otitis Media
Authors: Jack L. Paradise, Charles D. Bluestone, D. Kathleen Colborn, Beverly S. Bernard, Clyde G. Smith, Howard E. Rockette, Marcia Kurs-Lasky
Journal: JAMA (1999)

ContextAdenoidectomy and adenotonsillectomy are commonly performed in US children to reduce the occurrence of persistent or recurrent otitis media, but evidence supporting the efficacy of the operations is limited.ObjectivesTo test the efficacy of adenoidectomy and adenotonsillectomy in children with persistent or recurrent otitis media who had not previously undergone tube placement and to compare the relative efficacy of adenoidectomy alone vs adenotonsillectomy in such children.DesignTwo parallel randomized clinical trials.Setting and ParticipantsA total of 461 children aged 3 to 15 years were enrolled at Children's Hospital of Pittsburgh, Pa, between April 1980 and April 1994. Four hundred ten children were observed for up to 3 years.InterventionsChildren without recurrent throat infection or tonsillar hypertrophy (304 enrolled; 266 followed up) were randomized to either an adenoidectomy, adenotonsillectomy, or control group; children who had such conditions (157 enrolled; 144 followed up) were randomized to an adenotonsillectomy or control group.Main Outcome MeasuresOccurrence rate of episodes of acute otitis media by treatment group and estimated proportion of time with otitis media.ResultsIn both trials, most subjects were eligible because of recurrent acute otitis media, with or without persistent otitis media with effusion. A total of 47 children assigned to surgical treatment groups had no surgery. The efficacy of surgery in both trials was modest and limited mainly to the first follow-up year. The largest differences in that year were found in the 3-way trial between the adenotonsillectomy group and the control group: mean annual rate of episodes of acute otitis media, 1.4 vs 2.1 (P<.001); and mean estimated percentage of time with otitis media, 18.6% vs 29.9% (difference, 11.3%; 95% confidence interval, 4.4%-18.2%; P=.002). Perioperative and postoperative complications or other adverse events occurred not infrequently, especially among subjects undergoing adenotonsillectomy (14.6%).ConclusionsOur study showed limited and short-term efficacy of both adenoidectomy and adenotonsillectomy; given the risks, morbidity, and costs of these procedures, these data suggest that neither operation should ordinarily be considered as a first surgical intervention in children whose only indication is recurrent acute otitis media.
Acute Toxic and Withdrawal Reactions Associated with Drug Use and Abuse
Authors: E. J. KHANTZIAN
Journal: Annals of Internal Medicine (1979)

A variety of old and new substances and drugs with powerful psychotropic effects have come into common use during the past decade. Patterns of involvement include experimental, occasional, regular controlled, and regular uncontrolled use, with physical and psychologic dependence and toxic reactions as the frequent result of abuse patterns. This increase in drug use has affected all sectors of the medical profession, with physicians more likely to see patients who use and misuse various psychotropic substances. We discuss the diagnosis and management of common acute problems related to substance use, intoxication, overdose, and withdrawal. The drugs and substances discussed include the opiates, barbiturates (and other sedative hypnotic agents including alcohol and benzodiazepines), cocaine and the amphetamines, phencyclidine, hallucinogens, inhalents, and marijuana.
Excessive Supraventricular Ectopic Activity and Increased Risk of Atrial Fibrillation and Stroke
Authors: Zeynep Binici, Theodoros Intzilakis, Olav Wendelboe Nielsen, Lars Køber, Ahmad Sajadieh
Journal: Circulation (2010)

Background— Prediction of stroke and atrial fibrillation in healthy individuals is challenging. We examined whether excessive supraventricular ectopic activity (ESVEA) correlates with risk of stroke, death, and atrial fibrillation in subjects without previous stroke or heart disease. Methods and Results— The population-based cohort of the Copenhagen Holter Study, consisting of 678 healthy men and women aged between 55 and 75 years with no history of cardiovascular disease, atrial fibrillation, or stroke, was evaluated. All had fasting laboratory tests and 48-hour ambulatory ECG monitoring. ESVEA was defined as ≥30 supraventricular ectopic complexes (SVEC) per hour or as any episodes with runs of ≥20 SVEC. The primary end point was stroke or death, and the secondary end points were total mortality, stroke, and admissions for atrial fibrillation. Median follow-up was 6.3 years. Seventy subjects had SVEC ≥30/h, and 42 had runs of SVEC with a length of ≥20 SVEC. Together, 99 subjects (14.6%) had ESVEA. The risk of primary end point (death or stroke) was significantly higher in subjects with ESVEA compared with those without ESVEA after adjustment for conventional risk factors (hazard ratio=1.64; 95% confidence interval, 1.03 to 2.60; P =0.036). ESVEA was also associated with admissions for atrial fibrillation (hazard ratio=2.78; 95% confidence interval, 1.08 to 6.99; P =0.033) and stroke (hazard ratio=2.79; 95% confidence interval, 1.23 to 6.30; P =0.014). SVEC, as a continuous variable, was also associated with both the primary end point of stroke or death and admissions for atrial fibrillation. Conclusions— ESVEA in apparently healthy subjects is associated with development of atrial fibrillation and is associated with a poor prognosis in term of death or stroke.
Ethical Implications of Rejecting Patients for Clinical Trials
Authors: Thomas C. Chalmers
Journal: JAMA (1990)

Once in a blue moon, the request for an editorial to accompany a scientific article creates an opportunity to make an ethical point that is both new and important. Such an opportunity is presented by the article in this issue of<i>JAMA</i>entitled "The Quality of Life of Hemodialysis Recipients Treated With Recombinant Human Erythropoietin."<sup>1</sup>To quote from the "Patients and Methods" section, "The investigators, in consultation with representatives of the Food and Drug Administration, concluded that a randomized study involving the administration of a placebo was ethically indefensible." Presumably the ethical reasoning was that anyone asked to volunteer for randomization would be sacrificing his or her own health for the good of the study and future patients. That is the standard argument against randomization when there is a reasonable likelihood that the new therapy will be better than the old. It falls down when the expected improvement is entirely
Retrovirally transduced muscle-derived cells contribute to hematopoiesis at very low levels in the nonhuman primate model
Authors: Chunji Gao, Elizabeth M Kang, Ken Kuramoto, Brian A Agricola, Mark Metzger, Christof von Kalle, Robert E Donahue, John F Tisdale
Journal: Molecular Therapy (2003)

Recent studies have suggested a remarkable potential of adult stem cells from a variety of organs to give rise to cells of disparate organs, but evidence of such potential at a clonal level is lacking in most if not all studies to date. To assess directly the hematopoietic potential of muscle-derived cells in a relevant large animal, we initiated retroviral-tagging studies in the rhesus macaque to allow tracking at the clonal level by integration site analysis. Four rhesus macaques underwent transplantation with transduced muscle-derived cells after lethal irradiation followed by delayed infusion of an autologous hematopoietic graft. The first animal showed no evidence of hematopoietic recovery and, despite infusion of the backup hematopoietic graft, succumbed due to complications of prolonged cytopenias. In the remaining three animals, the overall contribution of retrovirally tagged muscle-derived cells toward hematopoiesis was exceedingly low. Retroviral integration site analysis among clonally derived muscle cells and bone marrow cells in vivo in one animal suggests a common source. These results demonstrate that harvesting disparate organs for cellular therapy is currently highly inefficient at best.
Summary of the National Toxicology Program's report of the endocrine disruptors low-dose peer review.
Authors: Ronald Melnick, George Lucier, Mary Wolfe, Roxanne Hall, George Stancel, Gail Prins, Michael Gallo, Kenneth Reuhl, Shuk-Mei Ho, Terry Brown, John Moore, Julian Leakey, Joseph Haseman, Michael Kohn
Journal: Environmental Health Perspectives (2002)

At the request of the U.S. Environmental Protection Agency (U.S. EPA), the National Toxicology Program organized an independent and open peer review to evaluate the scientific evidence on low-dose effects and nonmonotonic dose-response relationships for endocrine-disrupting chemicals in mammalian species. For this peer review, "low-dose effects" referred to biologic changes that occur in the range of human exposures or at doses lower than those typically used in the standard testing paradigm of the U.S. EPA for evaluating reproductive and developmental toxicity. The demonstration that an effect is adverse was not required because in many cases the long-term health consequences of altered endocrine function during development have not been fully characterized. A unique aspect of this peer review was the willing submission of individual animal data by principal investigators of primary research groups active in this field and the independent statistical reanalyses of selected parameters prior to the peer review meeting by a subpanel of statisticians. The expert peer-review panel (the panel) also considered mechanistic data that might influence the plausibility of low-dose effects and identified study design issues or other biologic factors that might account for differences in reported outcomes among studies. The panel found that low-dose effects, as defined for this review, have been demonstrated in laboratory animals exposed to certain endocrine-active agents. In some cases where low-dose effects have been reported, the findings have not been replicated. The shape of the dose-response curves for reported effects varied with the end point and dosing regimen and were low-dose linear, threshold-appearing, or nonmonotonic. The findings of the panel indicate that the current testing paradigm used for assessments of reproductive and developmental toxicity should be revisited to see whether changes are needed regarding dose selection, animal-model selection, age when animals are evaluated, and the end points being measured following exposure to endocrine-active agents.
Insulins for Insulin Resistance
Authors: DAVID M. NATHAN
Journal: Annals of Internal Medicine (1981)

Letters and Corrections1 December 1981Insulins for Insulin ResistanceDAVID M. NATHAN, M.D., LLOYD AXELROD, M.D.DAVID M. NATHAN, M.D.Search for more papers by this author, LLOYD AXELROD, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-95-6-785_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Dr. Galloway (1) notes in his comment on our article "U-500 Insulin in the Treatment of Antibody-Mediated Insulin Resistance" (2) that we did not compare equivalent doses of U-100 pork regular and U-500 pork regular insulins. He adds that for many years he and his colleagues have recommended the use of pork regular insulin to treat antibody-mediated insulin resistance (3-5) and contends that any concentrations of pork regular insulin would have been as effective as the U-500. Although we did not directly compare equivalent doses of the two concentrations of pork regular insulin, the data cited by...References1. GALLOWAY J. Pork insulin. Ann Intern Med. 1981;95:522-3. Letter. LinkGoogle Scholar2. NATHANAXELRODFLIERCARR DLJD. U-500 insulin in the treatment of antibody-mediated insulin resistance. Ann Intern Med. 1981;94:653-6. LinkGoogle Scholar3. BRESSLERGALLOWAY RJ. Insulin treatment of diabetes mellitus. Med Clin North Am. 1971;55:861-76. CrossrefMedlineGoogle Scholar4. GALLOWAYBRESSLER JR. Insulin treatment in diabetes. Med Clin North Am. 1978;62:663-80. CrossrefMedlineGoogle Scholar5. GALLOWAY J. When the patient is resistant or allergic to insulin. Med Times. 1980;108:91. MedlineGoogle Scholar6. AKREKIRTLEYGALLOWAY PWJ. Comparative hypoglycemic response of diabetic subjects to human insulin or structurally similar insulins of animal source. Diabetes. 1964;13:135-43. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Massachusetts General Hospital Boston, MA 02114 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1981Volume 95, Issue 6Page: 785-786KeywordsAttentionInsulinInsulin resistance Issue Published: 1 December 1981 PDF DownloadLoading ...
Endothelin receptor blockade improves endothelial function in human internal mammary arteries
Authors: S Verma
Journal: Cardiovascular Research (2001)

Objective: Endothelial dysfunction, specifically endothelium-derived contracting factors have been implicated in the development of arterial conduit vasospasm. The potent vasoconstrictor endothelin-1 (ET-1) has received much attention in this regard. The present study was designed to evaluate the role of ET-1 in the development of endothelial dysfunction in human internal mammary arteries (IMA). To this aim, we examined the effects of specific and non-specific ET-receptor antagonists on endothelial function (assessed using acetylcholine (ACh)-induced vasodilation) in segments of IMA obtained during coronary artery bypass graft (CABG) surgery. Methods: Vascular segments of IMA were obtained from 51 patients undergoing elective coronary artery bypass graft (CABG) surgery and in vitro endothelium-dependent and -independent responses to ACh and sodium nitroprusside (SNP) were assessed. Isometric dose response curves (DRC) to ACh and SNP were constructed in pre-contracted rings in the presence and absence of bosentan (ETA/B receptor antagonist, 3 μM), BQ-123 (ETA antagonist, 1 μM) and BQ-788 (ETB antagonist, 1 μM) using the isolated organ bath apparatus. Percent maximum relaxation (%Emax) and sensitivity (pEC50) were compared between interventions. Results: ACh caused dose-dependent endothelium-mediated relaxation in IMA (%Emax 43±4, pEC50 6.74±0.12). In the presence of bosentan, BQ-123 and BQ-788 ACh-induced relaxation was significantly augmented (%Emax bosentan 60±3, BQ-123 56±4, BQ-788 53±5 vs. control 43±4, P<0.05) without affecting sensitivity. The effects of these antagonists were endothelium-specific since endothelium-independent responses to SNP remained unaltered. Furthermore, the beneficial effects were independently and maximally mediated by ETA and ETB receptors (%Emax BQ-123 56±4 vs. BQ-788 53±5 vs. bosentan 60±3, P>0.05). Conclusions: These data uncover, for the first time, beneficial effects of ET receptor blockade on endothelial-dependent vasorelaxation in human IMA.
Displaced avulsion of the ischial apophysis: a hamstring injury requiring internal fixation.
Authors: C T Servant, C B Jones
Journal: British Journal of Sports Medicine (1998)

A case is reported of an adolescent sprinter who was chronically disabled by pain after non-operative management for an acute hamstring injury. He had sustained an avulsion fracture of the ischial apophysis with displacement of 2.5 cm. Avulsion fractures of the ischial apophysis with displacement of 2 cm or more are unusual, but they frequently result in a symptomatic non-union, and early diagnosis, open reduction, and internal fixation is to be encouraged.
Immune Checkpoints Score and CD8+ T Cells Infiltration Are Independent Prognostic Biomarkers in Resected Nsclc
Authors: M. Usó, E. Jantus-Lewintre, R. Sirera, S. Calabuig-Fariñas, A. Blasco, R. Guijarro, J. Forteza, C. Camps
Journal: Annals of Oncology (2015)
A Comparison of Global Versus Disease-Specific Quality-of-Life Measures in Patients With NIDDM
Authors: Robert M Anderson, James T Fitzgerald, Kimberlydawn Wisdom, Wayne K Davis, Roland G Hiss
Journal: Diabetes Care (1997)

OBJECTIVE This study was conducted to compare the Short Form 36 (SF-36) (a global measure of health-related quality of life) and the Diabetes Care Profile (DCP) (a diabetes-specific measure of self-care and diabetes-related quality of life) in patients with NIDDM. RESEARCH DESIGN AND METHODS This study was conducted as part of a larger study initiated in 1991 using a randomly selected sample of communities, physicians, and patients with diabetes located throughout Michigan. A total of 255 patients with NIDDM participated. The study examined the relationship between the two measures and diabetes variables, such as glycosylated hemoglobin level and number of complications. RESULTS The SF-36 and the DCP have both common and discrete measurement domains. Both instruments have acceptable subscale reliability. The DCP has predictive validity regarding glycemic control, whereas the SF-36 does not. Both measures correlate with the number of complications for patients who have NIDDM treated with insulin. CONCLUSIONS This study suggests that for examining relationships within diabetes, e.g., the impact of acute complications and/or regimen on quality of life, the DCP is the appropriate measure. Conversely, when examining relationships between the patient's experience of living with diabetes and quality of life and other chronic diseases, the SF-36 would be an appropriate measure. Both instruments can be used to illuminate the experience and behavior of patients living with and caring for NIDDM.
Abstract 3837: Protein Phosphatase PHLPP regulates protein translation and cell size through directly dephosphorylating p70 S6 kinase
Authors: Jianyu Liu, Payton Stevens, Tianyan Gao
Journal: Cancer Research (2011)

Abstract PHLPP (PH domain Leucine rich repeats Proten Phosphatase) is a family of Serine/Threonine protein phosphatases that has been identified to dephosphorylate Akt and PKC. We have shown previously that PHLPP functions as a tumor suppressor by negatively regulating Akt signaling in cancer cells. Here we report the identification of p70 S6 kinase (p70S6K) as a novel substrate of PHLPP. Purified PP2C domain of PHLPP specifically dephosphorylated p70S6K at Thr389 site in vitro and reduced its kinase activity towards purified S6 ribosomal protein. The interaction between PHLPP and p70S6K was detected by co-immunoprecipitation. Overexpression of both PHLPP isoforms resulted in a decrease in p70S6K phosphorylation. Furthermore, this PHLPP-mediated dephosphorylation of p70S6K was independent of its effect on Akt signaling, as PHLPP was capable to dephosphorylate p70S6K in Rictor knockout MEF cells. Interestingly, knockdown of PHLPP in 293E and certain colon cancer cells resulted in an increase in p70S6K phosphorylation and a decrease in Akt activity. Consistent with activation of a negative feedback loop via the p70S6K-IRS1-PI3K axis, we showed that IRS1 expression was significantly decreased in the PHLPP knockdown cells. Treating cells with Rapmycin, an mTOR inhibitor, to release the negative feedback regulation, the phosphorylation of Akt was restored more readily in the PHLPP knockdown cells compared to the control cells. Similarly, the phosphorylation of p70S6K induced by insulin was elevated whereas Akt activation was suppressed in PHLPP1 knockout MEF cells. Functionally, the amount of p70S6K bound to translation initiation factor eIF3 was decreased, whereas the amount of phosphorylated S6 ribosomal protein in the initiation complex bound to the cap structure was increased in PHLPP knockdown cells. This correlates with increased cap dependent translation as measured by a luciferase reporter assay. Moreover, the cell size and protein contents were increased in PHLPP knockdown and knockout MEF cells. Taken together, our results demonstrate that loss of PHLPP expression may activate p70S6K-dependent negative feedback loop, and PHLPP is a novel player involved in regulating protein translation initiation and cell size via direct dephosphorylation of p70S6K. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3837. doi:10.1158/1538-7445.AM2011-3837
Levosimendan vs. dobutamine: outcomes for acute heart failure patients on β‐blockers in SURVIVE†
Authors: Alexandre Mebazaa, Markku S. Nieminen, Gerasimos S. Filippatos, John G. Cleland, Jeffrey E. Salon, Roopal Thakkar, Robert J. Padley, Bidan Huang, Alain Cohen‐Solal
Journal: European Journal of Heart Failure (2009)
Recurrent Use of Disposable Syringe-Needle Units in Diabetic Children
Authors: Shahid Aziz
Journal: Diabetes Care (1984)

Fourteen insulin-dependent diabetic children reused their disposable syringe-needle units an average of 6.3 times per needle. Between uses, the needle was wiped with alcohol and stored in the refrigerator. There were no infections reported during the study for an average duration of 94 days. Dullness of the needle was the major reason for changing to a new one. Recurrent use of disposable needles for insulin injections appears safe in children and may be advised. It will help decrease some of the high cost of the daily care of a person with diabetes.
Remarks on BREECH PRESENTATION: FOETAL MORTALITY AND INJURIES
Authors: G. F. Gibberd
Journal: BMJ (1931)

Before discussing the various causes of foetal death and the types of foetal injury that may result from breech labour, we must be quite clear as to the frequency with which these catastrophies occur.I have drawn up a table illustrating the results to the foettus of breech labour in English maternity hospitals.tThese figures are obtained from the latest available annual reports of the hospitals in England which publish the necessary figures.It has not been possible to work out mortality rates for primiparae and for multiparae separately, since in some of these reports this information is not given.TABLE I. FOETAL AND NEO-
Human clusterin gene expression is confined to surviving cells during in vitro programmed cell death.
Authors: L E French, A Wohlwend, A P Sappino, J Tschopp, J A Schifferli
Journal: Journal of Clinical Investigation (1994)

Clusterin is a serum glycoprotein endowed with cell aggregating, complement inhibitory, and lipid binding properties, and is also considered as a specific marker of dying cells, its expression being increased in various tissues undergoing programmed cell death (PCD). However, no study has so far directly shown that cells expressing clusterin in these tissues are actually apoptotic as defined by morphological and biochemical criteria. We have studied cellular clusterin gene expression in vitro using three different models of PCD: (a) ultraviolet B (UV-B) irradiation of human U937, HeLa, and A431 cell lines, (b) in vitro aging of human peripheral blood neutrophils (PMNs), and (c) dexamethasone-induced cell death of the human lymphoblastoid cell line CEM-C7. In all three models, the classical morphological and biochemical features of PCD observed did not correlate with an increase, but with either a marked decrease or an absence of clusterin gene expression as assessed by Northern blot analysis. In situ hybridization of U937 and A431 cells after UV-B irradiation revealed, in addition, that only morphologically normal cells that are surviving continue to express the clusterin gene. Our results demonstrate that in the human myeloid, lymphoid, and epithelial cell types studied, clusterin gene expression is not a prerequisite to their death by apoptosis. In addition, and most interestingly, in situ hybridization of U937 and A431 cells revealed that only surviving cells express the clusterin gene after the induction of PCD, thus providing novel evidence suggesting that clusterin may be associated with cell survival within tissues regressing as a consequence of PCD.