海洛因成瘾者后扣带回结构和功能连接的磁共振研究

目的 应用基于体素的形态测量学和静息态功能磁共振研究海洛因成瘾者后扣带同结构和功能连接的变化情况.方法 14例海洛因成瘾者和13例正常对照者分别采集3DT1WI图像和静息态功能磁共振图像,对3DT1WI图像进行基于体素的形态测量学分析以了解相关脑区灰质密度和体积的变化,对功能磁共振图像分别以左、右后扣带同为感兴趣区与全脑的体素进行相关分析,比较海洛因成瘾组与正常对照组的后扣带回结构和功能连接的变化情况.结果 与正常对照相比,海洛因成瘾组的后扣带回灰质密度显著降低;以左侧后扣带回为感兴趣区进行功能连接分析,海洛因成瘾组左侧后扣带回与右侧颞叶的功能连接高于正常对照组,与右侧前额叶、丘腩以及左侧顶叶的功能连接明显低于正常对照组;以右侧后扣带回为感兴趣区进行功能连接分析,海洛因成瘾组右侧后扣带回与左侧额叶、左侧顶叶以及丘脑的功能连接明显低于正常对照组(双样本t检验,P<0.01).结论 海洛因成瘾者后扣带回的结构和功能连接异常,这与海洛因成瘾的脑结构和功能障碍以及奖赏系统障碍有关.

Abstract：

Objective To explore the abnormalities in the posterior cingulated cortex structure by voxel based morphometry(VBM)and changes of functional connectivity by resting-state functional magnetic resonance imaging(fMRI)in long-term heroin addictions.Methods High-resolution volumetric T1-weighted images and resting state fMRI examination were performed on 13 long-term heroin addicts and 14 matched healthy volunteers.The T1-weighted images were processed using optimized voxel-based morphometry to investigate abnormalities in the gray matter,at the sarne time,the posterior cingulated cortex was setted as the region-of-interest(ROI)seed,with which a whole-brain voxel temporal correlation in low frequency fMRI fluctuations was calculated,to find changes of the posterior cingulated cortex functional connectivity.Results Compared with the control group,gray matter concentration significantly decreased in the posterior cingnlated cortex,at the same time,the functional connectivity between the left posterior cingulated cortex and the right temporal lobe was increased,but the functional connectivity between the left posterior eingulated cortex and the left thalamus,the left parietal lobe,the left cerebrum were all decreased in heroin addicts.At the same time,the functional connectivity between the fight posterior cingulated cortex and the left thalamus,the left parietal lobe,the left frontal lobe were decreased in heroin addicts(t testing,P<0.01).Conclusion The structure and the functional connectivity in posterior cingulated cortex in long-term heroin addicts are changed,which may affect the dysfunction of the addictive brain and the function of reward mechanism.     

改良性治疗法联合西地那非治疗勃起功能障碍维吾尔族患者2505例回顾性分析

目的:性治疗法目前尚未普及,本研究旨在评价性治疗法联合西地那非治疗勃起功能障碍(ED)的疗效。方法:根据治疗方法的不同将在本院治疗随访过的3130例维吾尔族ED患者分成2组。对照组625例,单纯口服西地那非3个月;试验组2505例,采用性治疗法联合西地那非治疗3个月。采用国际勃起功能问卷表(IIEF-5)在各组治疗前、后进行疗效评估,并随访12个月。结果:对照组治疗前、后及在6个月、12个月随访的IIEF-5评分分别为12.80±3.76、18.10±2.61、17.35±2.73和16.64±2.63;试验组治疗前、后及在6个月、12个月随访的IIEF-5评分分别为12.73±3.52、19.06±4.07、19.86±2.42和20.47±2.38。两组治疗前后IIEF-5评分自身对比差异均有显著性(P<0.05)。组间比较,试验组较对照组6个月和12个月随访IIEF-5评分均有显著性差异(P<0.05)。结论:性治疗法联合西地那非治疗ED的效果优于单纯西地那非治疗,并在12个月的随访中稳定性良好。     

Infection and Malignancy Outweigh Cardiovascular Mortality in Kidney Transplant Recipients: Post Hoc Analysis of the FAVORIT Trial

Objective

Now that long-term survival after successful renal transplantation is no longer limited by excessive cardiovascular risk, the primary care physician should consider that infection and malignancy are leading noncardiovascular causes of death even in the recipient with diabetes.

Influence of Renal Function on the Pharmacokinetics,Pharmacodynamics, Efficacy,and Safety of Non–Vitamin K Antagonist Oral Anticoagulants

With the growing integration of non–vitamin K antagonist oral anticoagulants (NOACs) into clinical practice, questions have arisen regarding their use in special populations, including groups that may have been underrepresented in clinical trials. Patients with renal impairment, particularly in the lower echelons of renal function, are one such group. In an effort to elucidate the current evidence regarding the use of NOACs in patients with renal impairment, a systematic assessment of the literature was performed. The MEDLINE database was interrogated for studies and analyses evaluating the influence of renal function on the pharmacokinetics, pharmacodynamics, efficacy, and safety of NOACs published from January 1, 2000, through August 2, 2017. The 82 relevant publications retrieved highlight the diversity in the NOAC class regarding the impact of renal function on drug clearance, drug exposures, and clinical trial outcomes. In several large clinical trials, subgroup analyses revealed no significant differences when patients were stratified by creatinine clearance as a measure of renal function. Efficacy findings, in particular, were largely aligned with the overall population in the included studies. However, relative risks of bleeding were shown to vary, sometimes driven by changes in bleeding event rates in the comparator arm (eg, warfarin, enoxaparin). With few exceptions, minimal influence of mild renal impairment was observed on the relative efficacy and safety of NOACs. Taken together, the evidence suggests that the presence of renal impairment merits careful consideration of anticoagulant choice but should not deter physicians from appropriate use of NOACs.     

Early PREdiction of sepsis using leukocyte surface biomarkers: the ExPRES-sepsis cohort study

Purpose

Reliable biomarkers for predicting subsequent sepsis among patients with suspected acute infection are lacking. In patients presenting to emergency departments (EDs) with suspected acute infection, we aimed to evaluate the reliability and discriminant ability of 47 leukocyte biomarkers as predictors of sepsis (Sequential Organ Failure Assessment score?≥?2 at 24 h and/or 72 h following ED presentation).

Methods

In a multi-centre cohort study in four EDs and intensive care units (ICUs), we standardised flow-cytometric leukocyte biomarker measurement and compared patients with suspected acute infection (cohort-1) with two comparator cohorts: ICU patients with established sepsis (cohort-2), and ED patients without infection or systemic inflammation but requiring hospitalization (cohort-3).

Results

Between January 2014 and February 2016, we recruited 272, 59 and 75 patients to cohorts 1, 2, and 3, respectively. Of 47 leukocyte biomarkers, 14 were non-reliable, and 17 did not discriminate between the three cohorts. Discriminant analyses for predicting sepsis within cohort-1 were undertaken for eight neutrophil (cluster of differentiation antigens (CD) CD15; CD24; CD35; CD64; CD312; CD11b; CD274; CD279), seven monocyte (CD35; CD64; CD312; CD11b; HLA-DR; CD274; CD279) and a CD8 T-lymphocyte biomarker (CD279). Individually, only higher neutrophil CD279 [OR 1.78 (95% CI 1.23–2.57); P?=?0.002], higher monocyte CD279 [1.32 (1.03–1.70); P?=?0.03], and lower monocyte HLA-DR [0.73 (0.55–0.97); P?=?0.03] expression were associated with subsequent sepsis. With logistic regression the optimum biomarker combination was increased neutrophil CD24 and neutrophil CD279, and reduced monocyte HLA-DR expression, but no combination had clinically relevant predictive validity.

Conclusions

From a large panel of leukocyte biomarkers, immunosuppression biomarkers were associated with subsequent sepsis in ED patients with suspected acute infection.

Clinical trial registration

NCT02188992.

     

Synthetic and partially-purified adenylate cyclase-stimulating proteins from tumors associated with humoral hypercalcemia of malignancy inhibit phosphate transport in a PTH-responsive renal cell line

Hypophosphatemia and hyperphosphaturia characteristically occur in patients with humoral hypercalcemia of malignancy (HHM). To determine if a tumor product causes these abnormalities in phosphate metabolism, rather than, for example, hypercalcemia, we investigated the effect of partially-purified adenylate cyclase-stimulating activity (ACSA) from human and animal HHM-associated tumors on sodium-dependent phosphate transport (Na PiT) in a PTH-responsive renal epithelial cell line. Thirty minute exposure to 7 X 10(-10) MbPTH (1-34) equivalents of ACSA from the human and animal tumors, reduced NaPiT by 20% and 14%, respectively. We also recently isolated an adenylate cyclase-stimulating protein (hACSP) from two human tumors associated with HHM and identified a cDNA clone for this protein which encodes a 141 amino-acid peptide. Based on the deduced amino-acid sequence, we synthesized tyr36 (1-36) hACSP. This synthetic peptide induced a 22% decrease in the initial rate of NaPiT by the epithelial monolayer. Its inhibitory activity was roughly equipotent to that of bPTH (1-34). We conclude that the ACSP derived from HHM-associated tumors decreases phosphate transport in renal epithelial cells. This peptide appears to play a key role in mediating the changes in phosphate metabolism in this syndrome.     

Reassessment of vasodilator therapy in angina: Effects of oral isosorbide dinitrate and hydralazine on exercise tolerance in patients receiving propranolol

Nitrates, predominantly venodilators, are commonly used in the treatment of angina pectoris, whereas hydralazine, a potent systemic and coronary arterial vasodllator, is usually contraindicated. Hydralazine might be useful in therapy of angina H tachycardia could be prevented by beta adrenergic blockade. Consequently, treadmill exercise tolerance was determined in 20 patients with chronic stable angina during treatment with oral propranolol, 60 mg four times daily (control), propranolol plus 20 mg of oral isosorbide dinitrate, propranolol plus 100 mg of oral hydralazine, and all three drugs combined. The mean heart rate at rest in patients recelving propranolol was 54.0 ± 1.7 beats/min (mean ± standerd error of the mean). It increased 6.8 beats/min with the additlon of hydralazine (p < 0.005) and 7.2 beats/min with Isosorbide dlnitrate and hydralazine comblned (p < 0.005), but was unchanged with Isosorbide dinitrarate alone. Systoilc blood pressure decreased 13.5 mm Hg with Isosorbide dinitrate (p < 0.05) and 28.3 mm Hg with Isosorbide dinitrate and hydralazine combined (p < 0.005), but did not change significantly with hydralazine alone (average decrease 4.1 mm Hg). The mean duration of exercise increased by 24.1 seconds with Isosorbide dinitrate (p < 0.05), and almost twice that (42.4 seconds longer than the control value) with Isosorbide dinitrate and hydralazine (p < 0.005). With hydralazine alone, exercise duration was decreased by 24.7 seconds (p < 0.05). Rate-pressure product at symptom-tolerated maximal exercise was unchanged with Isosorbide dinitrarate or hydralazine alone, but lower than the control value with the two agents combined. It Is concluded that Isosorbide dinitrate Improves exercise tolerance in patients with angina who are being treated with propranolol, but hydralazine remains detrlmental despite the use of the beta blocking agent. However, when Isosorbide dinitrate is combined with hydralazine, the detrimental effects of hydralazine on exercise tolerance are reversed.     

An alarmingly high prevalence of diabetic nephropathy in Asian type 2 diabetic patients: the MicroAlbuminuria Prevalence (MAP) Study

Aim/hypothesis Microalbuminuria represents the earliest clinical evidence of diabetic nephropathy and is a marker of increased cardiovascular morbidity and mortality. Its early detection allows the implementation of individualised and aggressive intervention programmes to reduce cardiovascular risk factors. There is limited information on the prevalence of microalbuminuria among hypertensive type 2 diabetic patients in Asia.Methods This cross-sectional epidemiological study aimed to assess the prevalence of microalbuminuria and macroalbuminuria among consecutively screened hypertensive type 2 diabetic adult patients in 103 centres in 10 Asian countries or regions. Predictive factors for microalbuminuria and macroalbuminuria were characterised using a stepwise logistic regression model.Results A total of 6,801 patients were enrolled and 5,549 patients constituted the per-protocol population (patients with bacteriuria and haematuria were excluded). The prevalence of microalbuminuria was 39.8% (39.2–40.5; 95% CI) and the prevalence of macroalbuminuria was 18.8% (18.2–19.3; 95% CI). Only 11.6% of the patients had systolic and diastolic blood pressure below the 130/80 mm Hg target. In the multivariate analyses, the predictive factors for the presence of microalbuminuria were age, BMI, systolic blood pressure and ethnic origin. The highlighted predictive factors for the presence of macroalbuminuria were age, sex, ethnic origin, BMI, duration of diabetes, presence of diabetic complications, intake of diuretics, intake of calcium channel blockers, diastolic and systolic blood pressure.Conclusions/interpretation The high prevalence (58.6%) of micro or macroalbuminuria observed in these patients is alarming and indicates an impending pandemic of diabetic cardiovascular and renal diseases in Asia with its potential economic consequences.A.Y.T. Wu, F.A. de Leon and M.R. Weir received honoraria for speaking engagements and A. Rouillon is employed by Sanofi-Synthelabo Groupe.