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991.
Objective Hypoglycaemia‐associated autonomic failure (HAAF) with impaired neurogenic and neuroglycopaenic responses occurs in adults following recent, repeated hypoglycaemia. We aimed to evaluate whether HAAF also occurs in patients with infant‐onset congenital hyperinsulinism (CHI). Design, patients A controlled fast was performed in (i) seven CHI infants with initial symptomatic hypoglycaemia and three recent episodes of spontaneous recurrent hypoglycaemia each lasting <5 min and in (ii) seven infants with idiopathic ketotic hypoglycaemia for control. Measurements At the time of hypoglycaemia (blood glucose <3 mmol/l or clinical signs), blood was drawn for serum insulin, cortisol, glucagon, adrenalin and nor‐adrenalin. Signs of hypoglycaemia were documented. In CHI patients, the ABCC8 and KCNJ11 genes were analysed by denaturing high performance liquid chromatography (DHPLC) and/or direct bidirectional sequencing. Results Two CHI patients had a paternal ABCC8 mutation, five had no mutations. When repeated hypoglycaemia was provoked, all CHI patients exhibited a complete loss of clinical signs of hypoglycaemia, along with a global blunting of the counter‐regulatory hormones cortisol, glucagon, growth hormone, adrenalin and nor‐adrenalin responses (median values 256 nmol/l, 23 pmol/l, 5·6 mU/l, 390 pmol/l and 2·9 nmol/l, respectively), irrespective of mutational status. In the controls, hypoglycaemia was always clinically overt with normal counter‐regulatory cortisol, glucagon, adrenalin and nor‐adrenalin responses (530 nmol/l, 60, 920 pmol/l and 4·0 nmol/l, respectively). Conclusion Recurrent hyperinsulinaemic hypoglycaemia even of short duration blunts the autonomic, neuroglycopaenic and glucose counter‐regulatory hormonal responses in patients with infant‐onset CHI resulting in clinically silent hypoglycaemia. Tight, or continuous, glucose monitoring is therefore recommended, especially in conservatively treated patients.  相似文献   
992.
Circadian rhythms are ubiquitous in biological systems and regulate metabolic processes throughout the body. Misalliance of these circadian rhythms and the systems they regulate has a profound impact on hormone levels and increases risk of developing metabolic diseases. Melatonin, a hormone secreted by the pineal gland, is one of the major signaling molecules used by the master circadian oscillator to entrain downstream circadian rhythms. Several recent genetic studies have pointed out that a common variant in the gene that encodes the melatonin receptor 2 (MTNR1B) is associated with impaired glucose homeostasis, reduced insulin secretion, and an increased risk of developing type 2 diabetes. Here, we try to review the role of this receptor and its signaling pathways in respect to glucose homeostasis and development of the disease.  相似文献   
993.
Portal-systemic encephalopathy (PSE) is associated with increased brain turnover of serotonin (5-HT)in vivo but the brain 5-HT output seems to be unaltered. Recent results suggest, however, that an augmented neocortical 5-HT release in experimental chronic PSE may prevail under certain conditions. In the present study, neocortical extracellular 5-HT and 5-hydroxyindoleacetic-3-acid (5-HIAA) levels were measured in portacaval shunted (PCS) rats and sham-operated controls following local administration of p-chloroamphetamine (pCA) and d-fenfluramine (dFEN), two specific 5-HT releasing agents. The basal neocortical extracellular 5-HT concentrations were unaltered and the 5-HIAA levels were elevated in experimental PSE, supporting an unchanged brain 5-HT output despite elevated brain 5-HT metabolism. Perfusion with pCA or dFEN (5 μM; one 20-min pulse) produced marked increases in brain 5-HT release both in PCS and sham-operated rats compared with corresponding basal values. While no difference in the 5-HT response to dFEN administration was seen between sham (5-HT levels increased by 330%) and PCS (500%) rats, a clear difference (P<0.05) in the brain 5-HT output was observed between the two experimental groups following pCA perfusion (sham, 1100% versus PCS, 1470%). These results support our previous contention of an enhanced neocortical 5-HT output in experimental chronic PSE under certain pharmacological conditions.  相似文献   
994.
In the last few years,the advent of next generation sequencing(NGS) has revolutionized the approach to genetic studies,making whole-genome sequencing a possible way of obtaining global genomic information.NGS has very recently been shown to be successful in identifying novel causative mutations of rare or common Mendelian disorders.At the present time,it is expected that NGS will be increasingly important in the study of inherited and complex cardiovascular diseases(CVDs).However,the NGS approach to the genetics of CVDs represents a territory which has not been widely investigated.The identification of rare and frequent genetic variants can be very important in clinical practice to detect pathogenic mutations or to establish a profile of risk for the development of pathology.The purpose of this paper is to discuss the recent application of NGS in the study of several CVDs such as inherited cardiomyopathies,channelopathies,coronary artery disease and aortic aneurysm.We also discuss the future utility and challenges related to NGS in studying the genetic basis of CVDs in order to improve diagnosis,prevention,and treatment.  相似文献   
995.
996.

Aim

Vericiguat significantly reduced the primary composite outcome of heart failure (HF) hospitalization or cardiovascular death in the VICTORIA trial. It is unknown if these outcome benefits are related to reverse left ventricular (LV) remodelling with vericiguat in patients with HF with reduced ejection fraction (HFrEF). The aim of this study was to compare the effects of vericiguat versus placebo on LV structure and function after 8 months of therapy in patients with HFrEF.

Methods and results

Standardized transthoracic echocardiography (TTE) was performed at baseline and after 8 months of therapy in a subset of HFrEF patients in VICTORIA. The co-primary endpoints were changes in LV end-systolic volume index (LVESVI) and LV ejection fraction (LVEF). Quality assurance and central reading were performed by an echocardiographic core laboratory blinded to treatment assignment. A total of 419 patients (208 vericiguat, 211 placebo) with high-quality paired TTE at baseline and 8 months were included. Baseline clinical characteristics were well balanced between treatment groups and echocardiographic characteristics were representative of patients with HFrEF. LVESVI significantly declined (60.7 ± 26.8 to 56.8 ± 30.4 ml/m2; p < 0.01) and LVEF significantly increased (33.0 ± 9.4% to 36.1 ± 10.2%; p < 0.01) in the vericiguat group, but similarly in the placebo group (absolute changes for vericiguat vs. placebo: LVESVI −3.8 ± 15.4 vs. −7.1 ± 20.5 ml/m2; p = 0.07 and LVEF +3.2 ± 8.0% vs. +2.4 ± 7.6%; p = 0.31). The absolute rate per 100 patient-years of the primary composite endpoint at 8 months tended to be lower in the vericiguat group (19.8) than the placebo group (29.6) (p = 0.07).

Conclusions

In this pre-specified echocardiographic study, significant improvements in LV structure and function occurred over 8 months in both vericiguat and placebo in a high-risk HFrEF population with recent worsening HF. Further studies are warranted to define the mechanisms of vericiguat's benefit in HFrEF.  相似文献   
997.

Purpose

The goal of this study was to quantified the results of microsurgery, in all the patients with acromegaly treated by the same endocrinologist and the same surgeon between 1975 and 2015.

Methods

A series of 548 patients with acromegaly were operated and followed-up from 6 months to 40 years. Patients were selected according to five criteria: (1) Operated by the same surgeon. (2) No previous treatment. (3) Complete endocrinological preoperative studies including GH, OGTT, IGF-I, PRL test and TC/MRI. (4) Complete postoperative endocrinological evaluation for at least one determination of GH, OGTT, PRL test and IGF-I six months after surgery. (5) All the patients were supervised by the same endocrinologist.

Results

Microadenomas were present in 119 patients and 109 (91,5%) achieved remission. Non invasive macroadenomas were present in 200 patients and 164 achieved remission (82%). Results were worse for invasive macroadenomas but even with great invasions some patients achieved clinical remission. Follow-up range from 6 months to 40 years (mean 3.3?±?2.3) A long term follow-up of 15 years was achieved in 61 patients. Four of them had a recurrence 4, 7, 8, 12 years after surgery (6.5%). There was not mortality and the rate of complications was low.

Conclusions

Surgery remains the first line of therapy for a majority of acromegalic patients. This series proves to be very valuable in circumscribed adenomas but also in invasive tumours. Levels of GH and IGF-I were decreased in almost all the patients without remission.
  相似文献   
998.
999.
Introduction: Uptake of HIV tests is a challenging issue in vulnerable populations including immigrants, normally using standard diagnostic tools. Objectives of this study were to evaluate the acceptability of HIV rapid test; estimate the percentage of newly HIV diagnoses and evaluate knowledge, attitudes and perception (KAP) about HIV/AIDS and other STIs in a specific set of immigrants and vulnerable population in Rome (Italy). Methods: All immigrant and Italian people, aged 16–70 years, attending the infectious disease outpatient clinic of the National Institute for Health, Migration and Poverty (INMP) in Rome (Italy), during the period December 2012 to December 2013 were enrolled. HIV rapid testing was provided for free and patients were asked to fill in a questionnaire evaluating KAP about HIV/STIs. All patients with risky sexual behaviours or with a recent diagnosis of STIs were invited to come back after 3–6 months and a post-counselling questionnaire was offered. Results: Out of the total sample, 99.2% (n?=?825) accepted the “rapid test” and 10 new HIV diagnoses were found (1.22%; 95% CI 0.58%–2.22%). Three hundred and eighty-five participants (47%) answered the entry questionnaire and 58 (15%) completed the follow-up. Overall, we found high knowledge about HIV/AIDS; however, lower educational level and immigrant status were associated with poor knowledge about HIV, other STIs and prevention methods. Immigrants have lower perception of sexual risk and higher prejudice than Italians. Conclusions: Our study showed high acceptance of rapid test in this specific vulnerable population and this allowed to identify new HIV diagnoses in unaware people. Socioeconomic inequalities observed in the KAP questionnaire suggest the need for actions to support the reduction of cultural differences in knowledge of HIV/AIDS and for policies aimed at improving access to health services and preventions programmes of marginalized populations.  相似文献   
1000.

Background

The objective of this study is to evaluate use of the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) online risk calculator for estimating common outcomes after operations for gallbladder cancer and extrahepatic cholangiocarcinoma.

Methods

Subjects from the United States Extrahepatic Biliary Malignancy Consortium (USE-BMC) who underwent operation between January 1, 2000 and December 31, 2014 at 10 academic medical centers were included in this study. Calculator estimates of risk were compared to actual outcomes.

Results

The majority of patients underwent partial or major hepatectomy, Whipple procedures or extrahepatic bile duct resection. For the entire cohort, c-statistics for surgical site infection (0.635), reoperation (0.680) and readmission (0.565) were less than 0.7. The c-statistic for death was 0.740. For all outcomes the actual proportion of patients experiencing an event was much higher than the median predicted risk of that event. Similarly, the group of patients who experienced an outcome did have higher median predicted risk than those who did not.

Conclusions

The ACS NSQIP risk calculator is easy to use but requires further modifications to more accurately estimate outcomes for some patient populations and operations for which validation studies show suboptimal performance.  相似文献   
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