Rosiglitazone as an option for patients with acromegaly: a case series

<p>Abstract</p> <p>Introduction</p> <p>In the patient with acromegaly, pituitary surgery is the therapeutic standard. Despite undergoing surgery, a significant number of patients with acromegaly continue to have uncontrolled growth hormone secretion. These patients require other treatments such as external irradiation and/or drug therapy.</p> <p>Case presentation</p> <p>We present the clinical and laboratory responses to six months of treatment with rosiglitazone in four cases. In all four cases, the patients had persistent growth hormone overproduction despite previous surgical treatment and other conventional therapy. Case 1 is a 57-year-old Caucasian woman, case 2 is a 51-year-old Hispanic man, case 3 is a 32-year-old Hispanic woman, and case 4 is a 36-year-old Hispanic man. In three of these patients, basal and nadir growth hormone and insulin-like growth factor 1 levels were significantly decreased (<it>P </it>< 0.05 and <it>P </it>< 0.01, respectively).</p> <p>Conclusion</p> <p>Rosiglitazone could be a treatment option in select patients with acromegaly.</p

Corporate Culture of Contemporary Research University in Search of Complementarity of Humanitarian and Commercial Principles in Education (Russian Context)

Background: In the paper the formation of world-class research universities is analysed. The paper studies the history of the research university, prerequisites of its appearance, formation and its development toward modern research university. The modern research university is being cautiously viewed nowadays. The crisis of the university is its reality. The question of the corporate culture formation is now considered to be a topical matter in connection with globalization process, Methods: The authors implemented comparative analysis by comparing Humboldt's model of the research university and the modern one. Results: The comparison is made in regard to the idea of university, its criteria and mission. Special emphasis is laid on the analysis and comparison of corporate culture systems. Conclusions: Corporate culture is a novel criterion of the classical university that has recently arisen in the information society and now characterizes the university in a complementary way: on the one hand, as a competitive market entity, and on the other hand, as a guardian of its traditional, historically formed humanitarian criteria, ideas and mission. The following conclusion has been reached: the updated parameters have the identical form to those found by W. von Humboldt, only essence has changed

Rapid and sustained reduction of serum growth hormone and insulin-like growth factor-1 in patients with acromegaly receiving lanreotide Autogel® therapy: a randomized, placebo-controlled, multicenter study with a 52 week open extension

The study was designed to evaluate the long-term efficacy and safety of the 28-day prolonged-release Autogel formulation of the somatostatin analogue lanreotide (Lan-Autogel) in unselected patients with acromegaly. The study comprised four phases: washout; a double-blind comparison with placebo, at a single randomized dose (60, 90 or 120 mg) of Lan-Autogel; a single-blind, fixed-dose phase for four injections (placebo group was re-allocated to active treatment); and eight injections with doses tailored according to biochemical response. Serum samples were assessed for growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels, at weeks 4, 13, 14, 15, 16, 32 and 52. 108 patients were enrolled and 99 completed 52 weeks’ treatment. Four weeks after the first injection, serum GH levels decreased by >50% from baseline in 63% of patients receiving Lan-Autogel compared with 0% receiving placebo (P < 0.001). After four injections, 72% of patients had a >50% reduction in GH levels; 49% patients achieved GH levels ≤ 2.5 ng/ml; 54% had normalized IGF-1; and 38% achieved the combined criterion of GH level ≤ 2.5 ng/ml and normalized IGF-1. The corresponding proportions by week 52 were 82, 54, 59 and 43%, respectively. In patients not requiring dose escalation to 120 mg, 85% achieved biochemical control (combined criterion). Treatment was well tolerated by all patients. In conclusion, Lan-Autogel was effective in controlling GH and IGF-1 hypersecretion in patients with acromegaly and showed a rapid onset of action

Genetic variation in insulin‐induced kinase signaling

Individual differences in sensitivity to insulin contribute to disease susceptibility including diabetes and metabolic syndrome. Cellular responses to insulin are well studied. However, which steps in these response pathways differ across individuals remains largely unknown. Such knowledge is needed to guide more precise therapeutic interventions. Here, we studied insulin response and found extensive individual variation in the activation of key signaling factors, including ERK whose induction differs by more than 20‐fold among our subjects. This variation in kinase activity is propagated to differences in downstream gene expression response to insulin. By genetic analysis, we identified cis‐acting DNA variants that influence signaling response, which in turn affects downstream changes in gene expression and cellular phenotypes, such as protein translation and cell proliferation. These findings show that polymorphic differences in signal transduction contribute to individual variation in insulin response, and suggest kinase modulators as promising therapeutics for diseases characterized by insulin resistance.SynopsisGenetic variants contribute to individual variation in insulin response, including kinase activation, changes in gene expression and cell growth, suggesting kinase modulators as promising therapeutics for diseases characterized by insulin resistance.Extensive individual variation is observed in insulin‐induced activation of signal transduction.The variation in signaling response is propagated downstream to influence gene expression and cell growth.There is a genetic component to the individual differences in signaling and gene expression response to insulin.Genetic variants contribute to individual variation in insulin response, including kinase activation, changes in gene expression and cell growth, suggesting kinase modulators as promising therapeutics for diseases characterized by insulin resistance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112224/1/msb156250-sup-0001-EVFigs.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112224/2/msb156250.reviewer_comments.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112224/3/msb156250.pd

Gastrointestinal symptom severity in irritable bowel syndrome, inflammatory bowel disease and the general population

BackgroundIrritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) patients report similar gastrointestinal (GI) symptoms, yet comparisons of symptom severity between groups and with the general population (GP) are lacking.MethodsWe compared Patient‐Reported Outcomes Measurement Information System (PROMIS®) GI symptom scales measuring gastro‐esophageal reflux (GER), disrupted swallowing, diarrhea, bowel incontinence, nausea/vomiting, constipation, belly pain, and gas/bloating in: (i) USA GP sample, (ii) IBS patients, and (iii) IBD patients from tertiary care and community populations. Symptom severity scores were based on T‐score metric with mean 50±10 (standard deviation) relative to the GP.Key ResultsOf 1643 patients enrolled, there were 253 IBS patients (68% F, mean age 45±15 years), 213 IBD patients (46% F, mean age 41±14 years), and 1177 GP subjects (57% F, mean age 46±16 years). IBS patients reported greater severity of GER, disrupted swallowing, nausea/vomiting, belly pain, gas/bloating, and constipation symptoms than their IBD counterparts (all P<.05). Compared to the GP, IBD patients had worse belly pain, gas/bloating, diarrhea, and bowel incontinence, but less severe GER and disrupted swallowing (all P<.05), and IBS patients had more severe nausea/vomiting, belly pain, gas/bloating, and constipation (all P<.05). Women had more severe belly pain and gas/bloating than men, whereas men had more severe bowel incontinence (all P<.05).Conclusion & InferencesIBS and IBD are associated with more severe GI symptoms compared to the GP excluding esophageal symptoms. Unlike IBD, IBS is not characterized by observable GI inflammation but patients report more severe upper and lower GI symptoms.The PROMIS GI scales were used to determine gastrointestinal symptoms severity in patients. Unlike IBD, IBS is not characterized by observable gastrointestinal inflammation, but patients report more severe upper and lower gastrointestinal symptoms.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136712/1/nmo13003.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136712/2/nmo13003_am.pd

Construct Validity of the Patient‐Reported Outcomes Measurement Information System Gastrointestinal Symptom Scales in Systemic Sclerosis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109333/1/acr22337.pd

GH peak response to GHRH-arginine: relationship to insulin resistance and other cardiovascular risk factors in a population of adults aged 50–90

OBJECTIVE: To assess the GH response to GHRH-arginine in apparently healthy adults in relation to cardiovascular risk factors. DESIGN: Cross-sectional. PATIENTS: Eighty-six male and female volunteers aged 50–90. MEASUREMENTS: GH peak response to GHRH-arginine and cardiovascular risk factors, including obesity, insulin resistance, low levels of high density lipoprotein (HDL) cholesterol, elevated triglycerides, and hypertension. The primary outcome measurement was GH response to GHRH-arginine. The relationship between GH peak responses and cardiovascular risk factors was determined after data collection. RESULTS: GH peaks were highly variable, ranging from 2·3 to 185 µg/l (14% with GH peaks < 9 µg/l). An increasing number of cardiovascular risk factors were associated with a lower mean GH peak (P < 0·0001). By univariate analysis, fasting glucose, insulin, body mass index (BMI), HDL cholesterol and triglycerides were significantly associated with GH peak (all P < 0·0001). Multiple regression analysis revealed that fasting glucose, fasting insulin, BMI, triglycerides and sex accounted for 54% of GH peak variability. The role of abdominal fat as it relates to GH peak was explored in a subset of 45 subjects. Trunk fat and abdominal subregion fat measured by dual energy X-ray absorptiometry (DXA) were inversely related to GH peak (P < 0·008 and 0·001, respectively). Analysis of this subgroup by multiple regression revealed that subregion abdominal fat became the significant obesity-related determinant of GH peak, but still lagged behind fasting insulin and glucose. CONCLUSIONS: GH response to secretagogues was highly variable in apparently healthy adults aged 50–90 years. Peak GH was significantly related to fasting glucose, insulin, BMI, HDL cholesterol, triglycerides, trunk fat and abdominal subregion fat, with fasting glucose ranking first by multiple regression analysis. There was a strong relationship between cardiovascular risk factors and low GH, with individual risk factors being additive. Although these data do not differentiate between low GH being a cause or an effect of these cardiovascular risk factors, they indicate that the relationship between low GH and increased cardiovascular risk may be physiologically important in the absence of pituitary disease

Meta-Analysis on the Effects of Octreotide on Tumor Mass in Acromegaly

<div><h3>Background</h3><p>The long-acting somatostatin analogue octreotide is used either as an adjuvant or primary therapy to lower growth hormone (GH) levels in patients with acromegaly and may also induce pituitary tumor shrinkage.</p> <h3>Objective</h3><p>We performed a meta-analysis to accurately assess the effect of octreotide on pituitary tumor shrinkage.</p> <h3>Data Sources</h3><p>A computerized Medline and Embase search was undertaken to identify potentially eligible studies.</p> <h3>Study Eligibility Criteria</h3><p>Eligibility criteria included treatment with octreotide, availability of numerical metrics on tumor shrinkage and clear definition of a clinically relevant reduction in tumor size. Primary endpoints included the proportion of patients with tumor shrinkage and mean percentage reduction in tumor volume.</p> <h3>Data Extraction and Analysis</h3><p>The electronic search identified 2202 articles. Of these, 41 studies fulfilling the eligibility criteria were selected for data extraction and analysis. In total, 1685 patients were included, ranging from 6 to 189 patients per trial. For the analysis of the effect of octreotide on pituitary tumor shrinkage a random effect model was used to account for differences in both effect size and sampling error.</p> <h3>Results</h3><p>Octreotide was shown to induce tumor shrinkage in 53.0% [95% CI: 45.0%–61.0%] of treated patients. In patients treated with the LAR formulation of octreotide, this increased to 66.0%, [95% CI: 57.0%–74.0%). In the nine studies in which tumor shrinkage was quantified, the overall weighted mean percentage reduction in tumor size was 37.4% [95% CI: 22.4%–52.4%], rising to 50.6% [95% CI: 42.7%–58.4%] with octreotide LAR.</p> <h3>Limitations</h3><p>Most trials examined were open-label and had no control group.</p> <h3>Conclusions</h3><p>Octreotide LAR induces clinically relevant tumor shrinkage in more than half of patients with acromegaly.</p> </div

A consensus on the diagnosis and treatment of acromegaly complications

In March 2011, the Acromegaly Consensus Group met to revise and update the guidelines on the diagnosis and treatment of acromegaly complications. The meeting was sponsored by the Pituitary Society and the European Neuroendocrinology Association and included experts skilled in the management of acromegaly. Complications considered included cardiovascular, endocrine and metabolic, sleep apnea, bone diseases, and mortality. Outcomes in selected, related clinical conditions were also considered, and included pregnancy, familial acromegaly and invasive macroadenomas. The need for a new disease staging model was considered, and design of such a tool was proposed

Aspects of Black Hole Quantum Mechanics and Thermodynamics in 2+1 Dimensions

We discuss the quantum mechanics and thermodynamics of the (2+1)-dimensional black hole, using both minisuperspace methods and exact results from Chern-Simons theory. In particular, we evaluate the first quantum correction to the black hole entropy. We show that the dynamical variables of the black hole arise from the possibility of a deficit angle at the (Euclidean) horizon, and briefly speculate as to how they may provide a basis for a statistical picture of black hole thermodynamics.Comment: 20 pages and 2 figures, LaTeX, IASSNS-HEP-94/34 and UCD-94-1