Gaucher disease: Genetics,diagnosis and management

Gaucher disease is a storage disorder with varied manifestations. As the first storage disorder for which treatment is available, it is of considerable clinical and scientific importance. We review the history, clinical syndromes, molecular genetics and manifestations as well as modern diagnosis and therapy of the adult non-neuronopathic variant of Gaucher disease. (c) 2001 Prous Science. All rights reserved.     

Atherosclerotic renal artery stenosis: an update on diagnosis and management

Atherosclerotic renal artery stenosis (ARAS) is a progressive disease and it is usually associated with hypertension as well as with chronic kidney and cardiovascular disease. Although the anatomical lesions are relatively easy to depict, there is need to identify diagnostic methods to establish the functional significance of the stenosis and predict the response to revascularization. Over the last years, renal revascularization appears to be increasingly performed in patients with ARAS. However, controversy abounds as so far prospective, randomised trials did not document any benefit of revascularization with or without stenting plus optimal medical treatment over optimal medical treatment alone. In this review, we discuss the current data in the field of diagnosis and management of patients with ARAS.     

Renal disease in patients with HIV infection: epidemiology, pathogenesis and management

With the introduction of highly active antiretroviral therapy, we have witnessed prolonged survival with the potential for normal life expectancy in HIV-infected individuals. With improved survival and increasing age, HIV-infected patients are increasingly likely to experience co-morbidities that affect the general population, including kidney disease. Although HIV-associated nephropathy, the most ominous kidney disease related to the direct effects of HIV, may be prevented and treated with antiretrovirals, kidney disease remains an important issue in this population. In addition to the common risk factors for kidney disease of diabetes mellitus and hypertension, HIV-infected individuals have a high prevalence of other risk factors, including hepatitis C, cigarette smoking and injection drug use. Furthermore, they have exposures unique to this population, including antiretrovirals and other medications. Therefore, the differential diagnosis is vast.Early identification (through efficient screening) and definitive diagnosis (by kidney biopsy when indicated) of kidney disease in HIV-infected individuals are critical to optimal management. Earlier interventions with disease-specific therapy, often with the help of a nephrologist, are likely to lead to better outcomes. In those with chronic kidney disease, interventions, such as aggressive blood pressure control with the use of ACE inhibitors or angiotensin receptor antagonists where tolerated, tight blood glucose control in those with diabetes, and avoidance of potentially nephrotoxic medications, can slow progression and prevent end-stage renal disease. Only with greater awareness of kidney-disease manifestations and their implications in this particularly vulnerable population will we be able to achieve success in confronting this growing problem.     

Renal artery stenosis: today's questions

Renal artery stenosis remains a challenge, not only in terms of diagnosis but also in regard to when and how to treat this disease. Diagnostic tools that seemed promising have been unmasked as unreliable, and new treatment options such as angioplasty have failed to demonstrate their superiority. In the light of these disappointments, the most fundamental question appears to be: when is a stenosis relevant and therefore clinically significant, and how to proceed from there?     

急性肠系膜上动脉栓塞的诊治分析

目的探讨急性肠系膜上动脉栓塞早期诊断及综合治疗的临床疗效。方法 回顾性分析2005年5月～2008年4月,15例肠系膜上动脉栓塞的临床资料。结果 2例介入溶栓等治疗后痊愈,13例经手术治疗,分别采用局部肠切除、长肠管切除等,术后7例最终死亡。结论 早期诊断和以手术为主要手段的综合治疗可有助于提高存活率和治愈率。     

Emerging concepts in disease management: a role for antimicrobial therapy in coronary artery disease

Coronary artery disease, the leading cause of morbidity and mortality in developed countries, is a chronic inflammatory process that develops in response to a variety of injuries. A number of microbial organisms have been implicated in its pathogenesis. The strongest evidence to date for an association between an infectious agent and coronary heart disease is that for Chlamydia pneumoniae. Evidence implicating other microbial organisms is much less compelling. Sero-epidemiological and pathological data have linked infection with C. pneumoniae to atherosclerotic coronary artery disease. A possible mechanism by which C. pneumoniae may participate in the pathogenesis of atherosclerosis is through immune activation and the initiation of a chronic inflammatory state in the infected arterial wall. Locally secreted inflammatory cytokines trigger a cascade of secondary cellular processes that lead to characteristic structural changes. C. pneumoniae has been detected in atherosclerotic plaques and in the serum of patients with coronary artery disease. It induces foam cells (the hallmark of early atherosclerosis) and it markedly accelerates this disease process in animal models. C. pneumoniae has been associated with elevated levels of inflammatory cytokines and acute phase reactants. Data from three interventional studies in humans have suggested that treatment with antibiotics decreases inflammatory markers and perhaps influences the anti-C. pneumoniae antibody titers; however, adverse clinical events were not uniformly reduced in all trials. Two large prospective clinical trials, the WIZARD trial and ACES, are underway to confirm these preliminary findings and test the hypothesis that antibiotics may be beneficial in preventing or modifying the course of coronary artery disease. At present, antimicrobial therapy for atherosclerosis is not advocated outside of well-controlled research settings.     

Emerging concepts in disease management: a role for antimicrobial therapy in coronary artery disease

Coronary artery disease, the leading cause of morbidity and mortality in developed countries, is a chronic inflammatory process that develops in response to a variety of injuries. A number of microbial organisms have been implicated in its pathogenesis. The strongest evidence to date for an association between an infectious agent and coronary heart disease is that for Chlamydia pneumoniae. Evidence implicating other microbial organisms is much less compelling. Sero-epidemiological and pathological data have linked infection with C. pneumoniae to atherosclerotic coronary artery disease. A possible mechanism by which C. pneumoniae may participate in the pathogenesis of atherosclerosis is through immune activation and the initiation of a chronic inflammatory state in the infected arterial wall. Locally secreted inflammatory cytokines trigger a cascade of secondary cellular processes that lead to characteristic structural changes. C. pneumoniae has been detected in atherosclerotic plaques and in the serum of patients with coronary artery disease. It induces foam cells (the hallmark of early atherosclerosis) and it markedly accelerates this disease process in animal models. C. pneumoniae has been associated with elevated levels of inflammatory cytokines and acute phase reactants. Data from three interventional studies in humans have suggested that treatment with antibiotics decreases inflammatory markers and perhaps influences the anti-C. pneumoniae antibody titers; however, adverse clinical events were not uniformly reduced in all trials. Two large prospective clinical trials, the WIZARD trial and ACES, are underway to confirm these preliminary findings and test the hypothesis that antibiotics may be beneficial in preventing or modifying the course of coronary artery disease. At present, antimicrobial therapy for atherosclerosis is not advocated outside of well-controlled research settings.     

慢性肺心病合并冠心病的临床诊治分析

目的 探讨慢性肺心病合并冠心病的临床特点和诊断依据,总结分析其治疗方法,从而提高临床诊断率、降低病死率.方法 回顾性分析98例慢性肺心病合并冠心病患者的临床特点、心电图、X线摄片、超声心电图以及治疗资料.结果 肺心病出现典型心绞痛、心肌梗死,心电图左心导联动态缺血性改变、左前半或完全性左束支传导阻滞,反复出现左心衰竭伴有左心扩大者,应考虑合并冠心病.处理时要在常规治疗的基础上区别对待.结论 肺心病合并冠心病引起的心力衰竭患者,要根据诊断结果,在常规基础治疗的同时,针对病因与并发症取有效的个体化治疗措施进行处理,可获得较满意的临床效果.     

急性肠系膜上动脉闭塞性疾病的临床特点及诊治体会

目的：探讨急性肠系膜上动脉闭塞性疾病的临床特点及诊治方法。方法：回顾性分析天津医科大学总医院2003年11月至2011年3月收治的36例该病患者的临床资料。结果：本组36例患者,急性栓塞26例,慢性闭塞基础上的急性血栓形成10例;手术治疗27例,行单纯肠系膜上动脉取栓术4例,单纯坏死肠段切除术10例,肠切除及取栓术11例,肠切除及血管旁路术1例,肠切除、取栓及血管旁路术1例,治愈13例,死亡14例;保守治疗9例,好转7例,死亡2例;总死亡率44.4%。20例随访期间,术后再发本病者1例,经肠切除及肠系膜上动脉取栓术治愈,余经彩超证实均无再发肠系膜上动脉闭塞迹象。结论：对高度怀疑本病者应尽早行CTA或DSA检查,早期改善动脉供血、综合手段重建肠系膜上动脉是提高存活率和治愈率的关键。     

Primary blepharospasm: diagnosis and management

Primary blepharospasm is an adult-onset focal dystonia characterised by involuntary contractions of the orbicularis oculi muscles. Patients may have various types of movements arising from the different parts of the orbicularis oculi muscle. These include typical blepharospasm associated with Charcot's sign, pretarsal blepharospasm and flickering of the eyelids. Primary blepharospasm may be associated with so-called apraxia of eyelid opening as well as dystonia in the lower face, jaw or cervical muscles. Unless there are clinical clues to a symptomatic cause, adults presenting with blepharospasm do not require extensive aetiological investigation because the condition is rarely due to an identifiable condition. As the aetiology of primary blepharospasm is largely unknown, therapeutic approaches are symptomatic, with type A botulinum toxin being the treatment of choice.     

Medical management of the diabetic patient with coronary artery disease

The prevalence of type 2 diabetes is rising at an alarming rate worldwide. Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the diabetic population. Future CAD risk should be routinely assessed in patients with diabetes as specific subgroups might benefit from information derived from cardiac stress testing and other diagnostic procedures. Risk factor control is of paramount importance in all cases and it usually requires sustained lifestyle modifications, coupled with pharmacological interventions. Statins and angiotensin-converting enzyme (ACE) inhibitors are the first-line agents for the treatment of dyslipidaemia and hypertension, respectively. Microvascular, but not macrovascular, complications of diabetes are effectively prevented by good glycaemic control. Metformin is considered the first-choice agent in overweight diabetic subjects, while the role of thiazolidinediones is currently the focus of medical research. The diagnosis of acute coronary events in patients with diabetes is often challenging because of the high prevalence of silent ischaemia in these subjects. All acute cardiac events need to be promptly treated and myocardial reperfusion attempted without delay. Maintaining glucose levels as close to normal as possible, during and shortly after an acute event, improves prognosis in patients with diabetes. Risk factor control remains the cornerstone of secondary prevention; beta-blockers, ACE-inhibitors and antiplatelet agents confer additional symptomatic and survival benefit. Similar therapeutic principles also apply to patients with type 1 diabetes. This article addresses the complex problem of managing patients with diabetes and coronary artery disease.     

Celiac disease in pediatric patients with autoimmune hepatitis: etiology, diagnosis, and management

Celiac disease (CD) is defined as a permanent intolerance to ingested wheat gliadins and other cereal prolamins, occurring in genetically susceptible people. Persistent elevation of serum aminotransferase activity is expression of liver damage related to CD, which occurs in two distinctive forms. The most frequent is a mild asymptomatic liver injury, with a moderate increase of serum aminotransferase activities and a mild inflammatory portal and lobular infiltrate on liver biopsy (celiac hepatitis), reversible on a gluten-free diet (GFD). More rarely, severe and progressive inflammatory liver damage, induced by an autoimmune process and identified as autoimmune hepatitis (AIH), can develop and it is generally unaffected by gluten withdrawal. Surveys that included only pediatric patients report a wide range of prevalence of CD in AIH of 11.5-46% (mean 21.5%). CD and AIH share selected combinations of genes coding for class II human leukocyte antigens, which could explain their coexistence. Increased intestinal permeability and circulation of anti-tissue transglutaminase (tTG) have also been considered as further potential causes of liver damage in CD patients. tTG in the liver and in other extraintestinal tissues could modify other external- or self-antigens and generate different neo-antigens, which are responsible for liver injury in patients with CD. Patients with AIH represent a population at high risk for developing CD; screening for CD should be integrated into the diagnostic routine of all patients with AIH, with or without gastrointestinal manifestations, before starting immunosuppressive treatments. The only currently available treatment for CD is the GFD and the supportive nutritional care for iron, calcium, and vitamin deficiencies. Due to the difficulties of a GFD, in the past decade researchers have become increasingly interested in therapeutic alternatives to continuous or intermittent use of a GFD in patients with CD. Interventions addressed to correct the defect in the intestinal barrier are currently at the most advanced stage of clinical trials. The impact of a GFD on the outcome of AIH is not clear but it seems to be ineffective in the treatment of AIH. The early detection and treatment of CD, however, may prevent progression to end-stage liver failure.     

CT血管造影在冠状动脉疾病诊断的应用评价

目的探讨CT血管造影在冠状动脉疾病诊断中的应用价值。方法选取2013年12月~2014年12月在我院进行冠状动脉疾病诊断的64例患者作为研究对象,采用CT血管造影对患者的小钙化斑块情况进行检查,与重建厚度为3mm以及1mm的钙化斑块情况进行比较;对患者进行多层CT成像检查后,再进行冠状动脉造影检查,观察两种检查方法敏感度、特异度、阳性预测值与阴预测值及分级诊断有无差异,分析CT血管造影对冠状动脉疾病的诊断效果。结果使用CT造影检查患者的小钙化斑块以及重建后的钙化斑块情况,发现3mm组有40个小钙化斑块,钙化斑块54个;1mm组有54个小钙化斑块,64个钙化斑块。1mm组小钙化斑块和钙化斑块的检出率为100.00%明显高于3mm组的检出为84.38%,组间比较差异有统计学意义(P0.05)。CT诊断冠状动脉狭窄≥50%的总体敏感度、特异度、阳性预测值与阴性预测值分别为75.2%、80.1%、62.2%和89.7%,两种方法分级诊断具有高度的一致性。结论对冠状动脉疾病患者采用CT血管造影进行检测诊断,其检出率高,是一种有效、无创性的临床诊断方法,值得推广应用。     

Circulating miRNAs as biomarkers for early diagnosis of coronary artery disease

Introduction: Coronary artery disease (CAD) contributes to a huge number of human death worldwide. The early diagnosis can arrest the development of CAD and effectively lower the mortality rate. Recently, circulating miRNAs emerged as CAD biomarkers.

Area covered: Many efforts were paid to explore early diagnostic biomarkers of CAD. Some proteins have been used as diagnostic golden standard. However, the diagnostic and prognostic value of them is limited. MicroRNAs (miRNAs), a class of small noncoding RNAs, have been illustrated to regulate gene expression. The dysfunction of miRNAs is associated with CAD. MiRNAs presenting stably in body fluids are called circulating miRNAs. The altered expression of specific circulating miRNAs has been discovered in CAD and reported to affect the pathogenesis of CAD. We reviewed the recent data about circulating miRNAs regarding their potential roles in diagnosis, prognosis and therapeutic strategies for CAD. Additionally, we also summarized the current knowledge about circulating miRNA formation and detection.

Expert opinion: Compared with traditional diagnostic tools, circulating miRNAs have many strongpoints, suggesting that circulating miRNAs can serve as promising biomarkers for the early diagnosis and prognosis of CAD.     

Renal disease and acid-suppressing drugs

No comparative epidemiological data can be found in the literature on the renal safety of acid-suppressing drugs. We followed-up a cohort of close to 180,000 persons during periods of treatment and non-treatment with five anti-ulcer drugs to evaluate the risk of idiopathic acute renal failure and/or nephrotic syndrome. After reviewing medical records, five patients were found to be cases. Two presented with acute renal failure and three had nephrotic syndrome. Three cases occurred during periods of non-exposure to anti-ulcer drugs. Two cases occurred during current use of ranitidine: one of acute renal failure and one of nephrotic syndrome. No case was encountered during treatment with cimetidine, famotidine, nizatidine or omeprazole. The incidence of idiopathic renal disease in the general population was 1 per 100,000 person-years. The relative risk associated with use of acid-suppressing drugs was 1.8 (95% CI, 0.3-10.7) compared to non-use. These results do not suggest a major increased risk for acute renal injury and/or nephrotic syndrome associated with use of anti-ulcer drugs.     

Characterization of arbutamine: A novel catecholamine stress agent for diagnosis of coronary artery disease

Arbutamine, 1,2-Benzenediol,4-[1-hydroxy-2-[[4-(4-hydroxyphenyl)butyl[amino]ethyl]rsqb;rsqb; hydrochloride, (R), is a new catecholamine being developed as a pharmacologic stress agent for the diagnosis of coronary artery disease and myocardial ischemia. The pharmacology of arbutamine was studied in vitro using receptor binding assays and functional bioassays of α- and β-adrenoceptor activity, and in vivo using the hemodynamic responses to intravenous infusion in anesthetized and conscious dogs. In isolated membranes, receptor binding studies demonstrated K_i values of 196 ± 12 nM and 147 ± 11 nM for β₁- and β₂-adrenoceptors, and 265 ± 4 nM and 867 ± 40 nM for α₁- and β₂-adrenoceptors, suggesting that arbutamine is a mixed β₁₊₂-adrenoceptor agonist with significant affinity for β₁-adrenoceptors. This was supported by in vitro bioassay data, where arbutamine increased spontaneous atrial rate (β₁-activity, ED₅₀ = 16 ± 6 nM), relaxed isolated tracheal rings (β₂-activity, ED₅₀ = 13 ± 5 nM), and contracted aortic rings (α-activity, ED₅₀ = 430 ± 80 nM), indicating 25–30-fold selectivity for β-adrenoceptor activation. In conscious or anethetized dogs, arbutamine elicited dose-dependent increases in heart rate and LV dP/dt with little fall in mean arterial pressure. The data demonstrate that arbutamine exhibits similar degrees of intropic and chronotropic activity, while eliciting less peripheral vasodialation than isoproteronal and less inotropic activity than dobutamine. Moreover, there was rapid termination of the tachycardia, as heart rate resolved to 50% of the maximal effect within 7.2 ± 1.1 min following arbutamine, compared to 5.5 ± 1.0 min following isoproterenol and 5.9 ± 1.4 min following dobutamine. This hemodynamic profile and rapid pharmacodynamic offset makes arbutamine ideally suited for use as a pharmacologic stress agent.