Biochemical and molecular characterization of a new sporadic glucose-6-phosphate dehydrogenase variant described in Italy: G6PD Modena

Summary. A new glucose-6-phosphate dehydrogenase variant detected in an Italian man from the Po delata is described and designated as G6PD Modena. Biochemical characterization of the variant enzyme revealed an activity 21% of normal, a slow electrophoretic mobility, increased K_m value for NADP, decreased K_m value for G6P and a complete absence of NADPH inhibition, which could account for the apparently nonhaemolytic feature of this variant. The cloning and sequencing of the G6PD Modena allele showed a GC transition at nucleotide 844 in exon VIII causing a Asp His amino acid substitution. On the basis of biochemical characterization, G6PD Modena is classified as a genuine variant but it has the same mutation as G6PD Seattle-like.     

清肺止咳丸配合穴位贴敷治疗咳嗽变异性哮喘的研究

目的：探讨清肺止咳丸配合穴位贴敷对咳嗽变异性哮喘的治疗作用。方法：选取2013年1月-2014年9月的120例咳嗽变异性哮喘患者,随机分为两组,每组各60例,治疗组应用清肺止咳丸配合穴位贴敷治疗,对照组应用肺力咳胶囊治疗,两组均以10 d为一疗程,2个疗程后统计结果。结果：治疗组总疗效及主要症状评分、LCQ测评及各单项指标评分、小气道通气状况与对照组比较差异有统计学意义（P<0.05）,两组患者外周血嗜酸粒细胞计数均有改善。结论：清肺止咳丸配合穴位贴敷治疗咳嗽变异性哮喘有较好的临床疗效。     

Collapsing focal segmental glomerulosclerosis in a patient with oral cavity cancer: A case report

Rationale:Focal segmental glomerulosclerosis (FSGS) is one of the most common glomerular diseases, leading to end-stage renal disease. Among the 5 variants of FSGS, the collapsing variant is rare and has the worst prognosis. Solid and hematologic malignancies are associated with glomerular diseases, such as membranous nephropathy, minimal change disease, and FSGS. However, squamous cell carcinoma of the oral cavity is rarely associated with nephrotic syndrome, especially FSGS.Patient concerns:A 55-year-old woman diagnosed with oral cavity cancer presented with generalized edema with heavy proteinuria and renal dysfunction after neoadjuvant chemotherapy and wide surgical excision.Diagnosis:Renal biopsy shows segmental or global collapse of glomerular capillaries with marked hyperplasia and swelling of overlying epithelial cells, suggesting a collapsing variant of FSGS.Interventions:After the renal biopsy, we prescribed oral prednisolone at a dose of 1 mg/kg/day. Despite immunosuppressive treatment, renal function deteriorated, and hemodialysis was started.Outcomes:After 23 sessions of hemodialysis and high-dose oral glucocorticoid treatment, renal function gradually improved, and oral glucocorticoid therapy was discontinued after 8 months. Currently, this patient is in a cancer-free state and has normal renal function without proteinuria.Lessons:Unusual collapsing FSGS might be associated with neoadjuvant chemotherapy and wide surgical excision in patients with oral cavity cancer. Proper diagnostic workup, such as renal biopsy and high-dose glucocorticoid therapy, might have helped recover from nephrotic syndrome and acute renal injury in cancer patients.     

Precision Medicine Approaches to Vascular Disease: JACC Focus Seminar 2/5

In this second of a 5-part Focus Seminar series, we focus on precision medicine in the context of vascular disease. The most common vascular disease worldwide is atherosclerosis, which is the primary cause of coronary artery disease, peripheral vascular disease, and a large proportion of strokes and other disorders. Atherosclerosis is a complex genetic disease that likely involves many hundreds to thousands of single nucleotide polymorphisms, each with a relatively modest effect for causing disease. Conversely, although less prevalent, there are many vascular disorders that typically involve only a single genetic change, but these changes can often have a profound effect that is sufficient to cause disease. These are termed “Mendelian vascular diseases,” which include Marfan and Loeys-Dietz syndromes. Given the very different genetic basis of atherosclerosis versus Mendelian vascular diseases, this article was divided into 2 parts to cover the most promising precision medicine approaches for these disease types.     

Cardiac Genetic Predisposition in Sudden Infant Death Syndrome

Background

Sudden infant death syndrome (SIDS) is a leading cause of postneonatal mortality. Genetic heart diseases (GHDs) underlie some cases of SIDS.

Angiographic documented coronary arterial spasm in absence of critical coronary artery stenoses in a patient with variant angina episodes during exercise and dobutamine stress echocardiography

Dobutamine stress echocardiography is widely performed as a useful diagnostic tool in patients with known or suspected coronary artery disease. Dobutamine induced myocardial ischaemia is frequently associated with ST segment depression. ST segment elevation is uncommon and is almost always associated with prior myocardial infarction or transient total coronary occlusion. Dobutamine induced ST segment elevation in absence of significant coronary artery disease is a rare condition and is supposed to be a consequence of severe coronary artery spasm. The case of a 58 year old man with variant angina episodes at rest, during exercise test, and dobutamine stress echocardiography is reported, in whom coronary spasm without significant coronary artery stenoses was documented angiographically.


Keywords: coronary spasm; variant angina; Prinzmetal angina; dobutamine stress echocardiography; exercise test     

江苏省2010年O1群霍乱疫情分离株病原学特征分析

目的:分析2010年江苏省O1群霍乱疫情分离株病原学特征,为霍乱疫情分析及临床治疗提供实验室依据?方法:对2010年江苏省O1群霍乱疫情分离株进行毒力基因检测?ctxB基因序列分析?抗生素敏感性实验?脉冲场凝胶电泳分子分型分析?结果:2010年江苏省O1群霍乱疫情分离株均携带毒力基因ctxA?ace?zot? toxR? tcpI?ompU?rtxC?tcpAEL?hlyAEL,且CTXB氨基酸序列为古典型;对庆大霉素?诺氟沙星?环丙沙星100%敏感,对复方新诺明?链霉素100%耐药,且均为多重耐药株;除VC201014外,其余14株菌脉冲场凝胶电泳图谱相似度达100%?结论:2010年9月初至10月初,发生在江苏省徐州?淮安?宿迁?南京4个地市的O1群霍乱疫情可能是有关联的暴发流行,2010年8月底发生在连云港的O1群霍乱疫情是一起散发疫情,与上述四地的霍乱疫情可能没有流行病学关联,所有疫情的病原均为非典型埃尔托型霍乱弧菌,庆大霉素?诺氟沙星?环丙沙星可作为临床治疗的首选药物?     

The Return of Actionable Variants Empirical (RAVE) Study,a Mayo Clinic Genomic Medicine Implementation Study: Design and Initial Results

Objectives

To identify clinically actionable genetic variants from targeted sequencing of 68 disease-related genes, estimate their penetrance, and assess the impact of disclosing results to participants and providers.

Clinical Implications of Clonal Hematopoiesis

Clonal hematopoiesis (CH)—an expansion of blood cells derived from a single hematopoietic stem cell—is a defining feature of hematologic cancers, but recently CH was also found to be a frequent consequence of aging. When aging-associated CH results from acquisition of a somatic mutation in a driver gene associated with leukemia, and this mutation is present at a variant allele frequency of at least 0.02 (2%) yet the patient does not meet World Health Organization diagnostic criteria for a hematologic neoplasm, this state is termed clonal hematopoiesis of indeterminate potential (CHIP). CHIP is present in approximately 10% to 15% of people older than 70 years and more than 30% by age 85 years and represents a precursor state for neoplasia akin to monoclonal gammopathy of undetermined significance. Recently, CHIP was unexpectedly found to be an important risk factor for cardiovascular events, with accumulating evidence supporting a mechanism of accelerated atherogenesis as a result of vascular inflammation driven by clonally derived monocytes/macrophages. Risk factors for CHIP include aging, male sex, cigarette smoking, and a common germline variant in the telomere-associated gene TERT. Clonal hematopoiesis can also occur after cytotoxic chemotherapy or radiotherapy for a solid tumor, after hematopoietic stem cell transplant, in the context of aplastic anemia, or after induction chemotherapy for acute leukemia; in each setting, CH has distinct clinical implications. This review summarizes recent studies of CH and CHIP and outlines challenges in clinical management of affected patients.