PSMA6/PSMC6/PSMA3基因多态性与系统性红斑狼疮发病的相关性

目的:明确蛋白酶体(PSM)相关基因单核苷酸多态性与中国人群系统性红斑狼疮(SLE)的相关性。方法:PCR扩增101例SLE患者和143名正常对照者外周血目的基因片段,通过二代测序对目的基因片段进行测序检测蛋白酶体20 s亚单位和相关ATP酶基因的4个目标位点PSMA6(rs2277460),PSMA3(rs2348071),PSMC6(rs2295826,rs2295827)的基因型及等位基因频率。结果:SLE组及对照组中rs2277460(GG,GA、AA)基因型频率分别为97.22%,1.85%%,0.93%和96.5%,3.5%,0;rs2348071AA,AG,GG分别为30.56%、53.7%、15.74%和33.57%、50.35%、16.08%;rs2295826AA,AG,GG分别为75.93%、24.07%、0和69.23%、29.37%、1.4%;rs2295827CC、CT、TT分别为78.7%、19.45%、1.85%和76.22%、20.98%、2.8%,均无统计学差异(P0.05)。结论:PSMA6/PSMC6/PSMA3 SNPs可能与SLE的发病无关。     

Impact of a Standardized Titration Protocol with Carvedilol in Heart Failure: Safety,Tolerability, and Efficacy—A Report from the GESICA Registry

Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA) studied whether a standardized protocol for the initiation and titration of the β-blocker carvedilol in a multicenter, open-label program would optimize β-blocker use in heart failure (HF) patients. The program included: (1) the carvedilol initiation and titration period, and (2) long-term follow-up at 6 and 12 months. Of 1299 patients in the registry, 504 were excluded due to current therapy; of the remaining 795 eligible patients, 293 were excluded due to contraindications. Of the included patients with follow-up data (n = 316), 93.3% tolerated carvedilol initiation and 47.7% of the patients reached the target dose of 50 mg/day for a mean dose of 39 mg/day. Rates were comparable in the elderly (n = 83), of which 53% achieved a target dose for a mean dose of 43.08 mg/day. This protocol improved therapy rates and achieved target doses quickly (average of 4 visits). Concomitant medications did not have to be adjusted and there were low withdrawal rates (10%) and hospital admissions (7.2%) for HF. Patients were able to maintain carvedilol therapy at 6 and 12 months. These results indicate that a standardized titration protocol, as used in GESICA, for the initiation and titration of β-blockers is well tolerated and may improve β-blocker use in carefully selected heart failure patients.The study authors are members of the GESICA Steering Committee and Subcommittees     

Automobile driving and implantable defibrillators

The consequences of implanting an automatic cardioverter defibrillator (ICD) on vehicle driving in France are poorly known. This retrospective study examined the behaviour at the wheel of ICD recipients who were recommended to abstain from driving for 3 to 6 months after device implantation. The study population included 98 patients (mean age = 59.5 +/- 14.8 years) followed for a mean of 24. +/- 23.9 months, who underwent ICD implant for ventricular tachycardia (65% of patients ventricular fibrillation (15%), syncope (8%), as part of a research protocol of myocardial cell transplantation 6%, or for primary prevention (5%). The underlying heart disease was ischemic in 59% of patients dilated cardiomyopathy in 11%,hypertrophic cardiomyopathy in 8%, valvular in 6%. Brugada syndrome in 4%, right ventricular arrhythmogenic cardiomyopathy in 2%, and miscellaneous disorders in 9% of patients. Five patients died without post mortem interrogation of the ICD. Only 28% of drivers remembered, and 13% observed, the recommended driving limitations. However, 45% (the oldest) claimed to drive prudently. During follow-up, 47% of patients received an ICD shock. Their mean it ventricular ejection fraction was 34 +/- 14%, versus 43 +/- 18% in patients who received no ICD therapy (p = 0.015). Syncope occurred in 16% who received ICD shocks. Shocks were delivered during driving in 6 patients, without consequent accident. Despite their non-observance of recommended driving limitations. ICD recipients suffered few traffic accidents. Legislation in France should reproduce the guidelines issued by European professional societies and enacted by the British laws.     

Associations analysis of GSTM1, T1 and P1 Ile105Val polymorphisms with carpal tunnel syndrome

Oxidative stress was related with carpal tunnel syndrome (CTS). We aimed to clarify the associations between glutathione S-transferase (GST)M1, GSTT1 and GSTP1-Ile105Val polymorphisms and CTS. One hundred-forty patients with CTS and 97 healthy controls were enrolled in this study. Tinel and Phalen signs were noted as positive or negative. Functional and clinical status of patients was evaluated by the Boston Questionnaire. The intensity of hand and/or wrist pain was evaluated on 10 cm visual analog scale (VAS). We applied the polymerase chain reaction (PCR) to determine the polymorphisms of the GSTM1 and GSTT1 and the PCR-restriction fragment length polymorphism method for detecting the GSTP1-Ile105Val polymorphism. The M1 null genotype was significantly higher in patients with CTS compared to healthy controls, and the M1 null genotype seemed to increase the risk of CTS approximately two-fold (P?=?0.011; odds ratio (OR)?=?1.98; 95 % confidence interval (CI) 1.17–3.36). The M1 null, T1 present combined genotype was significantly higher in patients with CTS compared to healthy controls (P?=?0.043); however, it seemed not to increase the risk of CTS (P?=?0.14; OR?=?0.62; 95 % CI 0.33–1.76). We found significantly higher levels of the VAS, Boston Symptom Severity Scale and Phalen sign in patients with the Ile/Val or the Val/Val genotypes compared to those in patients with the Ile/Ile genotype (P?=?0.003, 0.004 and 0.044, respectively). We proposed that genes involved in the protection from oxidative stress may influence the susceptibility, clinical and functional status of CTS. The GSTM1 null genotype may be related with the development of CTS, whereas the Val allele of GSTP1-Ile105Val polymorphism may be associated with worse functional and clinical status in CTS.     

The role of MBL,PCT, CRP,neutrophil–lymphocyte ratio,and platelet lymphocyte ratio in differentiating infections from flares in lupus

Clinical Rheumatology - The distinction between infection and flare in systemic lupus erythematosus (SLE) has always been a dilemma for clinicians as the clinical and biochemical profiles overlap....     

Post‐renal transplant erythrocytosis: A case report

PTE is defined as hematocrit >51% or hemoglobin >17 g/dL after renal transplantation. Risk factors include native kidneys with adequate erythropoiesis pretransplant, smoking, renal artery stenosis, and cyclosporine treatment. We report the case of a 14‐yr‐old female kidney transplant patient, with triple therapy immunosuppression and stable graft function who developed PTE at 12 months post‐transplant with hemoglobin 17.3 g/dL, hematocrit 54.2%, stable graft function, and normotensive with normal cardiac echocardiogram and erythropoietin levels. The only risk factor found was tobacco use. As she had no spontaneous improvement, enalapril treatment was started at 19 months post‐transplant with a hemoglobin level of 17.5 g/dL and hematocrit 53%; by 23 months post‐transplant, hemoglobin lowered to 15 g/dL and hematocrit to 44.5% and continued to be in normal range thereafter. PTE is a rare condition in childhood and can be successfully treated with enalapril.     

Acute pancreatitis during sickle cell vaso-occlusive painful crisis

Sickle cell disease is characterized by chronic hemolytic anemia and vaso-occlusive painful crisis. The vascular occlusion in sickle cell disease is a complex process and accounts for the majority of the clinical manifestations of the disease. Abdominal pain is an important component of vaso-occlusive painful crisis and may mimic diseases such as acute appendicitis and cholecystitis. Acute pancreatitis is rarely included as a cause of abdominal pain in patients with sickle cell disease. When it occurs it may result form biliary obstruction, but in other instances it might be a consequence of microvessel occlusion causing ischemia. In this series we describe four cases of acute pancreatitis in patients with sickle cell disease apparently due to microvascular occlusion and ischemic injury to the pancreas. All patients responded to conservative management. Acute pancreatitis should be considered in the differential diagnosis of abdominal pain in patients with sickle cell disease.     

The interplay between metabolic alterations,diastolic strain rate and exercise capacity in mild heart failure with preserved ejection fraction: a cardiovascular magnetic resonance study

Background

Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. However its role in mild HF with preserved ejection fraction (HFpEF) is uncertain. We measured myocardial triglyceride content (MTG) in HFpEF and assessed its relationships with diastolic function and exercise capacity.

Methods

Twenty seven HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent ¹H-cardiovascular magnetic resonance spectroscopy (¹H-CMRS) to measure MTG (lipid/water, %), ³¹P-CMRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking cardiovascular magnetic resonance (CMR) imaging for diastolic strain rate.

Results

When compared to controls, HFpEF had 2.3 fold higher in MTG (1.45?±?0.25% vs. 0.64?±?0.16%, p?=?0.009) and reduced PCr/ATP (1.60?±?0.09 vs. 2.00?±?0.10, p?=?0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO₂ max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO₂ max.

Conclusions

Myocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF.