1,720,974 research outputs found
Epinephrine's ketogenic effect in humans is mediated principally by lipolysis.
To quantify epinephrine's effects on acetoacetate and beta-hydroxybutyrate kinetics, we infused subjects with 0.3 and 2.5 micrograms/min epinephrine, either alone or with a concomitant somatostatin infusion with insulin, glucagon, and growth hormone replaced at postabsorptive levels (islet clamp). Additional subjects received no epinephrine but sequential infusions of heparin plus 10% Intralipid at rates of 0.5 and 3.0 ml/min. Both epinephrine and Intralipid increased ketone body appearance (unaffected by islet clamp), augmented the interconversion rates between ketone bodies and, during the 2.5 micrograms/min infusion, caused a marked increase in beta-hydroxybutyrate appearance. The fraction of plasma free fatty acid (FFA) flux appearing as plasma ketones increased from 6 to 7% in the basal state to 11% at the high-epinephrine infusion. This fraction was also unaffected by the islet clamp and was not different from values obtained at similar Intralipid plus heparin-induced elevations in plasma FFA levels. We conclude that epinephrine's ketogenic effect in humans is primarily the result of its lipolytic effect, is accompanied by a significantly increased rate of ketone body interconversion, is manifest largely as an increase in plasma beta-hydroxybutyrate appearance at high plasma epinephrine values, and is not limited by portal insulin at post-absorptive levels.</jats:p
Brief twice-weekly episodes of hypoglycemia reduce detection of clinical hypoglycemia in type 1 diabetes mellitus.
We tested the hypothesis that as few as two weekly brief episodes of superimposed hypoglycemia (i.e., doubling the average frequency of symptomatic hypoglycemia) would reduce physiological and behavioral defenses against developing hypoglycemia and reduce detection of clinical hypoglycemia in patients with type 1 diabetes mellitus (T1DM). Compared with nondiabetic controls, six patients with well-controlled T1DM (HbA1c, 7.5 +/- 0.7% [mean +/- SD]) exhibited absent glucagon responses and reduced epinephrine (P = 0.0027), norepinephrine (P = 0.0007), pancreatic polypeptide (P = 0.0030), and neurogenic symptom (P = 0.0451) responses to hypoglycemia as expected. In these patients, 2 h of induced hypoglycemia (50 mg/dl, 2.8 mmol/l) twice weekly for 1 month, compared in a random-sequence crossover design with an otherwise identical 2 h of induced hyperglycemia (150 mg/dl, 8.3 mmol/l) twice weekly for 1 month, further reduced the epinephrine (P = 0.0001) and pancreatic polypeptide (P = 0.0030) responses, tended to further reduce the norepinephrine and neurogenic symptom responses to hypoglycemia, and reduced cognitive dysfunction during hypoglycemia (P = 0.0271), all assessed in the investigational setting. In the clinical setting, induced hypoglycemia did not alter overall glycemic control, but did reduce the total number of symptomatic hypoglycemic episodes detected by the patients from 49 to 30 per month and lowered the mean +/- SE self-monitored blood glucose level during symptomatic hypoglycemia from 51 +/- 2 mg/dl (2.8 +/- 0.1 mmol/l) to 46 +/- 3 mg/dl (2.6 +/- 0.2 mmol/l) (P < 0.01). It also reduced the proportion of low regularly scheduled self-monitored values that were symptomatic by approximately 33%. Thus as little as doubling the frequency of symptomatic hypoglycemia further reduced both the key epinephrine response and clinical awareness of developing hypoglycemia, changes reasonably expected to increase the risk of severe iatrogenic hypoglycemia in T1DM
Role of GH in regulating nocturnal rates of lipolysis and plasma mevalonate levels in normal and diabetic humans.
Insulin independence after islet transplantation into type I diabetic patient
Effective clinical trials of islet transplantation have been limited by the inability to transplant enough viable human islets into patients with type I (insulin-dependent) diabetes mellitus to eliminate their exogenous insulin requirement. We report the first type I diabetic patient with an established kidney transplant on basal cyclosporin immunosuppression who was able to eliminate the insulin requirement after human islet transplantation into the portal vein. We successfully isolated ∼800,000 islets that were 95% pure from 1.4 cadaver pancreases containing 121 U of insulin. Islets were proven viable by in vitro insulin response to glucose challenge. After 7 days of 24°C culture, the islets were transplanted into the portal vein under local anesthesia. Seven days of Minnesota antilymphoblast globulin (20 mg/kg) administration followed the islet transplantation, with maintenance of the cyclosporin. Blood glucose was kept under strict control via intravenous insulin for 10 days posttransplantation, when all insulin therapy was stopped. Off insulin, the average 24-h blood glucose level remained <150 mg/dl, with the fasting glucose level at 115 ± 6 mg/dl and the 2-h postprandial level at 141 ± 8 mg/dl for 22 days posttransplantation (the time of this study). The C-peptide values post-Sustacal testing, although initially rising slower, exceeded the normal range, with peak values of 1.0-1.8 pmol/ml. This preliminary result represents the first essential step required to determine the feasibility of islet transplantation by future clinical trials
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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