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Adequacy of current postglucose GH nadir limit (< 1 microg/l) to define long-lasting remission of acromegalic disease
No full textObjective: Some authors proposed to lower the present postglucose GH nadir cut-off (i.e. 0.26 μg/l in 24 patients (Group B). Group B had only slightly higher IGF-1 SDS (0.4 ± 1.0 vs. - 0.1 ± 1.0, P = ns) and lower body mass index (BMI) than Group A (26.2 ± 2.4 vs. 30.6 ± 4.5 kg/m2, P < 0.005). GH nadir positively correlated with IGF-1 (P < 0.05, r = 0.32) and negatively with BMI (P < 0.05, r = 0.42). In Phase 2, all patients had IGF-1 levels in the normal range and GH nadir < 1 μg/l, both parameters being even lower than those found at the time of remission. No patient had either clinical or neuroradiological evidence of disease recurrence. Conclusions: The current GH nadir limit is still adequate to define both short- and long-lasting remission of acromegaly, independently of the type of definitive treatment. Patients with the lowest GH nadir should probably be monitored long-term for adequacy of their GH secretion
Stimulatory effects of ghrelin on circulating somatostatin and pancreatic polypeptide levels
Full text linkGhrelin, the recently identified endogenous ligand of the GH secretagogue receptor, is a gut-brain peptide with endocrine, orexigenic, and gastrointestinal effects. In rodents it increases circulating gastrin and insulin levels, whereas in man it appears to decrease insulin secretion despite a rise in blood glucose levels. The aim of the present study was to evaluate the effects of ghrelin administration on total circulating somatostatin (SS), pancreatic polypeptide (PP), and gastrin levels compared with those elicited on insulin, glucose, and GH. Eight healthy volunteers of normal weight (four women and four men) were injected with 3.3 μg/kg ghrelin or saline after an overnight fast on 2 different days. Blood was taken every 15 min for 1 h and then every 30 min for 2 h. As expected, ghrelin injection elicited a prompt GH and glucose increase with a peak at 30 min and an insulin decrease with a nadir at 60 min. Gastrin concentrations were not modified, whereas significant rises were observed in both SS (in a biphasic pattern with peaks at 15 and 120 min) and PP (which increased promptly with a peak at 15 min). A significant negative correlation was found between SS (first peak) and insulin changes (r = -0.86; P < 0.01). In conclusion, this study clearly demonstrates that ghrelin stimulates SS and PP release in man. Although the underlying mechanisms and biological significance of these pharmacological effects remain to be elucidated, a causal relationship between the SS increase and the insulin changes may be hypothesized. Finally, these findings strongly support ghrelin's postulated role in linking the endocrine control of energy balance and growth with the regulation of gastrointestinal functions
Growth hormone therapy in GH-deficient adults: continuous vs alternate-days treatment
No full textIn the present report, we have compared 12 months of rhGH therapy given daily (D) at the beginning and then on alternate days (A) to 20 subjects with severe adult-onset GH deficiency (GHD). Aim of the study was to establish whether the lower frequency injection regimen is as effective as the daily dose. Measurements included: IGF-I levels, body composition (BF%), lipid profile, insulin sensitivity by homeostasis model assessment (HOMA-IR) and quantitative insulin check index (QUICKI), as well as thyroid function. Evaluation on A therapy was performed both 12 and 36 hours after the last rhGH injection. The final rhGH dose was 0.3 ± 0.1 mg/day. During A, the dose used in D was doubled and given on alternate days. Recombinant hGH given during the A period induced changes in IGF-I levels, BF% and lipid profile comparable to daily treatment. HOMA-IR increased similarly after both regimens, though QUICKI did not significantly change. A significant reduction in serum FT4 levels occurred after both D and A therapy, so that an adjustment of L-T4 replacement dose in 5 of 20 patients was necessary. No differences were found in the various parameters after 12 and 36 hours post rhGH injection. In conclusion, rhGH therapy given on alternate days is clinically effective and may result in improved patient compliance. Monitoring glucose tolerance and thyroid function while on rhGH is essential
Long-term evaluation of postoperative acromegalic patients in remission with previous and newly proposed criteria
No full textCriteria to define remission of acromegaly have changed over years. Since 2000, criteria for cure are normal IGF-I levels and a nadir GH after oral glucose tolerance test (OGTT) of less than 1 μg/liter, although recent studies have suggested to lower this cutoff value. This study reevaluated long-term disease activity of acromegalic patients, who were previously considered in remission, using these criteria. The study included 70 of 146 patients operated on between 1984 and 1996 who were considered cured based on normal IGF-I levels, GH values less than 2.5 μg/liter, and/or disappearance of abnormal GH response to TRH/GnRH. Among these 70 patients, 16 were lost to follow-up, three died, and 11 (one of whom had disease recurrence) only gave a phone interview. Forty patients participated in the study and were reevaluated for IGF-I levels and post-OGTT GH nadir after 14.3 ± 4.2 (mean ± SD) yr from surgery. In all patients, normal IGF-I levels and a post-OGTT GH nadir of less than 1 μg/liter were found. In particular, 19 patients had a GH nadir of less than 0.19 μg/liter, i.e. the upper limit (mean + 2 SD) found in 30 controls, whereas 21 patients had a nadir between 0.19 and 0.77 μg/liter. No significant differences in hormonal parameters and comorbidities between the two subgroups were observed. These data showed that lowering the post-OGTT GH cutoff value within the normal range does not seem to better discriminate patients with different disease activity or long-term recurrence risk. Copyrigh
Evaluation of insulin resistance in acromegalic patients before and after treatment with somatostatin analogues
Full text linkMany studies have recently shown that simple computer-solved indices, based on fasting glucose and insulin levels, closely mirror the euglycemic clamp technique in studying insulin resistance or pancreatic insulin secretion. Few data are at present available on the evaluation of these novel indices in acromegalic patients, known to be GH-dependent insulin-resistant subjects, in particular during medical treatment with somatostatin analogues. Indeed, these drugs are able to inhibit not only GH and IGF-I levels, but also insulin and glucagon pancreatic secretion, with contrasting effects on glucose metabolism. In this study, insulin resistance was evaluated by the homeostasis model assessment (HOMA-IR) and insulin sensitivity by quantitative insulin check index (QUICKI) in 27 normoglycemic acromegalic patients, before and after 6-month therapy with somatostatin analogues (lanreotide-SR 30-60 mg every 7-28 days in 15 and octreotide-LAR 20-30 mg every 28 days in 12). Thirty-five age- and sex-matched healthy subjects and 17 surgically treated acromegalic patients (5 cured and 12 not cured) were studied as control groups. Before medical treatment, HOMA-IR was higher in acromegalic patients than in healthy controls (4±3 vs 1.7±0.7, p<0.05), while QUICKI was lower (0.33±0.04 vs 0.36±0.03, p<0.05). During medical therapy, HOMA-IR decreased to 2.4±1.6 (p<0.05) and became similar to that recorded in both healthy subjects and surgically treated patients. However, fasting glucose was increased and fasting insulin was decreased. QUICKI did not significantly change from basal values. No differences were observed between patients who normalized or not hormonal levels. The effects of the 2 drugs, though higher glucose levels were seen in patients treated with octreotide-LAR. In conclusion, this study demonstrates that medical treatment is able to improve insulin resistance, even if only successful surgery is able to completely normalize both HOMA-IR and QUICKI
New therapeutic options for acromegaly
No full textAcromegaly is a slowly developing disfiguring disease characterized by chronic growth hormone (GH) and insulin-like growth factor-I (IGF-I) excess and caused by a pituitary somatotroph adenoma. It is associated to 2- to 3 fold increased mortality, compared to normal population, mostly due to cardiovascular and cerebro-vascular diseases, and to several co-morbid systemic illnesses, such as diabetes mellitus, hypertension, severe arthropathies, a specific cardio-myopathy, goitre, sleep-apnoea, intractable headache. The morbidity and excess mortality of acromegaly are usually the consequence of the metabolic actions of excess GH and IGF-I secretion, while only in rare patients mortality is due to the mass effects of the pituitary tumour. Since, serum IGF-I concentrations within age-adjusted normal range, and a tight GH control have to be achieved to normalize life-expectancy in these patients, an aggressive, and often multi-modality treatment is required for acromegaly. In recent years, new drugs, and new formulations of old drugs, have been developed that are able to effectively inhibit GH secretion or GH action, and may represent important adjuncts or even alternatives to the traditional approaches of surgery and radiotherapy. This review briefly summarizes the therapeutic options nowadays available for acromegaly. A brief note about innovative drugs under study, is also given
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
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