A Homozygous Frameshift Mutation in the HOXC13 Gene Underlies Pure Hair and Nail Ectodermal Dysplasia in a Syrian Family

Pure hair and nail ectodermal dysplasia (PHNED) is a rare genetic disorder characterized by hypotrichosis or complete alopecia, as well as nail dystrophy. Mutations in the type II hair keratin gene KRT85 and the HOXC13 gene on chromosome 12q have recently been identified in families with autosomal‐recessive PHNED. In the present study, we have analyzed a consanguineous Syrian family with an affected girl having complete alopecia and nail dystrophy since birth. The family clearly showed linkage to chromosome 12q13.13–12q14.3, which excluded the KRT85 gene. Sequencing of another candidate gene HOXC13 within the linkage interval identified a homozygous frameshift mutation (c.355delC; p.Leu119Trpfs*20). Expression studies in cultured cells revealed that the mutant HOXC13 protein mislocalized within the cytoplasm, and failed to upregulate the promoter activities of its target genes. Our results strongly suggest crucial roles of the HOXC13 gene in the development of hair and nails in humans.     

Nonoperative Removal of Bilateral Intrahepatic Biliary Stones by Endoscopic Electrohydraulic Lithotripsy

We report the successful treatment of bilateral intrahepatic biliary stones by endoscopic electrohydraulic lithotripsy (EHL). EHL is a useful procedure by which large stones can be fragmented easily and complete removal of stones can be attained.     

Usefulness of hydrophilic vs lipophilic statins after acute myocardial infarction: subanalysis of MUSASHI-AMI.

BACKGROUND: Statins are widely used to reduce blood levels of low-density lipoprotein-cholesterol (LDL-C). Each statin has unique pharmacokinetic properties; lipophilicity is one such property and relates to tissue selectivity. METHODS AND RESULTS: The Multicenter Study for Aggressive Lipid-lowering Strategy by HMG-CoA Reductase Inhibitors in Patients with Acute Myocardial Infarction (MUSASHI-AMI) trial evaluated the effect of discretional statin treatment initiated within 96 h after onset of acute myocardial infarction (AMI) in Japanese patients. To clarify whether statin lipophilicity affects prognosis, a post hoc analysis of the MUSASHI-AMI database was performed. Patients who were assigned to receive statin were separated into 2 groups according to the lipophilicity of the statins they were administered: lipophilic statins (atorvastatin, fluvastatin, pitavastatin and simvastatin; LS group; n=131) or hydrophilic statins (pravastatin; HS group; n=110). There was no difference in baseline LDL-C concentrations between the 2 groups. Although LDL-C was decreased more potently in the LS than HS groups (-34% vs -19%; p=0.0069), acute coronary syndrome events tended to occur less frequently (3.6% vs 9.9%; p=0.0530) and the incidence of new Q-wave appearance in electrocardiogram was significantly lower (75% vs 89%; p=0.0056) in the HS than LS groups. CONCLUSIONS: In normocholesterolemic Japanese patients after AMI, hydrophilic pravastatin could be superior to lipophilic statins at preventing new Q-wave appearance and reducing cardiovascular events.     

Metastatic renal cell carcinoma presenting as multiple pleural tumours

A 66-year-old man was admitted with dyspnoea. Chest X-ray and chest computed tomography (CT) demonstrated a left-sided pleural effusion and multiple tumours, suggesting malignant mesothelioma in the left pleural space, but there were no pulmonary lesions. However, abdominal CT revealed a right renal tumour. An ultrasonography-guided needle biopsy of the pleural mass provided evidence of metastatic renal cell carcinoma (RCC). The pleural lesions dramatically decreased in size following right radical nephrectomy and subsequent interferon-alpha treatment. While the thorax is a frequently affected site of RCC, sole pleural metastases are rare and are often secondary to lung involvement. Batson's plexus, a network of vertebral valve-less veins with multiple connections, is likely responsible for the contralateral pleural metastases of RCC.     

Effect of pravastatin on the development of diabetes and adiponectin production

In the West of Scotland Coronary Prevention Study (WOSCOPS), treatment of hypercholesterolemic men with pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, reduced their likelihood to progress to diabetes mellitus by 30%. However, the mechanism of this effect of pravastatin has not been investigated. In the current study, we examined the effect of pravastatin on the development of diabetes in obese diabetic mice, and on the insulin-induced glucose uptake and adiponectin production. Pravastatin treatment attenuated the development of diabetes in db/db and high fat/high sucrose diet-fed C57BL/6J mice. An in vivo glucose transport assay showed that pravastatin upregulated glucose uptake in adipose tissue. Insulin-stimulated glucose uptake was enhanced in primary adipocytes isolated from pravastatin-treated mice. Pravastatin treatment increased adiponectin production in 3T3-L1 adipocytes. Plasma adiponectin levels were significantly increased in pravastatin-treated mice. Analyses of plasma samples from the WOSCOPS biobank indicated a significant increase of plasma adiponectin levels with pravastatin treatment (placebo -0.28+/-0.34 microg/ml versus pravastatin +1.47+/-0.33 microg/ml, p=0.0003). Taken together, our findings suggest that pravastatin may have beneficial effects on adipose tissue, which may partly explain the reduction of the development of diabetes by pravastatin treatment.     

Effect of statin on restenosis after radius stent implantation in patients with acute coronary syndrome

Despite reports that statin treatment reduces the rate of coronary restenosis with a balloon expandable stent, there is no evidence that statins affect the incidence of restenosis with a self-expanding Radius stent. Ninety-five patients with acute coronary syndrome who had been implanted with a Radius stent were classified into two groups: those with hyperlipidemia and initial statin treatment (statin group, n = 38) and those without statin treatment (comparative group, n = 57). At six months after stent implantation, the rate of coronary restenosis was significantly lower in the statin group (10.5%) than control group (28.1%) (p = 0.033), while there were no differences in morphology, maximal inflation pressure or stent size between the two groups. Interestingly, there was no difference in the serum lipid profile between the two groups at the 6-month follow-up, although the statin group had a significantly lower rate of restenosis. In conclusion, initial statin therapy reduced the rate of coronary restenosis even when a Radius stent was implanted.     

Metabolic syndrome and lifestyle modification

A clustering of metabolic abnormalities such as dyslipidemia, hypertension, and diabetes mellitus, all of which are major risk factors for cardiovascular disease (CVD), occurs more often than by chance. Numerous epidemiological studies, as well as basic researches, have revealed that visceral fat accumulation is closely involved in this risk clustering. This morbid condition is now well recognized as the metabolic syndrome. The concept of the metabolic syndrome, i.e., the involvement of visceral adiposity in the clustering of CVD risk factors, implies that an effective CVD risk reduction will be accomplished by an intervention to reduce visceral fat deposits. The primary strategy of the intervention is lifestyle modification, which can be put into practice in healthcare fields, without necessity of medical treatment. Now that CVD is a leading global health burden, the metabolic syndrome attracts increasing attention in the world. To take global action against the syndrome, several working groups developed its internationally unified diagnostic criteria. Most recently, the International Diabetes Federation (IDF) and the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) jointly proposed the criteria, although some cautions will be needed in their practical use. In this review, we mainly focus on the findings observed in clinical and epidemiological studies, to discuss a practical strategy of the management of the metabolic syndrome in healthcare fields.