A New Ultrasonographic “Fluttering Sign” for Hepatic Hemangioma

The aim of the study described here was to clarify the diagnostic value of the fluttering sign, a new sign that characterizes hepatic hemangiomas in gray-scale ultrasonography (US). It refers to a phenomenon in which the speckled echogenicity inside the hemangioma changes continuously and seems to be moving. A total of 172 hemangiomas diagnosed with contrast-enhanced US were evaluated. The fluttering sign was found in 123 of 172 hemangiomas (71.5%). Its prevalence was significantly higher than that of the marginal strong echo (89/172, 51.7%, p < 0.001), posterior acoustic enhancement (103/172, 59.9%, p = 0.031) and chameleon sign (100/172, 58.1%, p = 0.013). In addition, the fluttering sign was observed significantly more frequently in mixed or hypo-echoic tumors than in hyper-echoic tumors (p < 0.001), relatively large tumors (p < 0.001) and tumors that were less than 5 cm from the body surface (p = 0.015). The fluttering sign in gray-scale US has great potential to be a new complementary sign for the diagnosis of hemangioma.     

Prediction of Treatment Efficacy and Telaprevir-Resistant Variants after Triple Therapy in Patients Infected with Hepatitis C Virus Genotype 1

It is often difficult to predict the response to telaprevir-pegylated interferon (PEG-IFN)-ribavirin triple therapy and the appearance of telaprevir-resistant variants. The present study determined the predictive factors of a sustained virological response (SVR) to 12- or 24-week triple therapy (T12PR12 or T12PR24, respectively) in 194 Japanese patients infected with hepatitis C virus genotype 1b (HCV-1b). The study also evaluated whether ultradeep sequencing technology can predict at baseline the emergence of resistant variants after the start of therapy. Analysis of the data of the entire group indicated that an SVR was achieved in 78% of the patients. Multivariate analysis identified IL28B rs8099917 (genotype TT), the substitution of amino acid (aa) 70 (Arg70), response to prior treatment (naive or relapse), PEG-IFN dose (≥1.3 μg/kg of body weight), and treatment regimen (T12PR24) as significant determinants of SVR. Among patients of the T12PR24 group, 92% with genotype TT achieved an SVR, irrespective of a substitution at aa 70. In patients with the non-TT genotype, an SVR was achieved in 76% of those with Arg70, while only 14% of patients with the non-TT genotype, Gln70(His70), and nonresponse to ribavirin combination therapy achieved an SVR. Ultradeep sequencing was conducted for 17 patients who did not achieve an SVR to determine the emergence of resistant variants during therapy. De novo resistant variants were detected in 16 of 17 patients (94%), regardless of the variant frequencies detected at baseline. In conclusion, the results indicate that the response to triple therapy can be predicted by the combination of host, viral, and treatment factors and that it is difficult to predict at baseline the telaprevir-resistant variants that emerge during triple therapy, even with the use of ultradeep sequencing.     

Ketogenic diet for refractory epilepsy with MEHMO syndrome: Caution for acute necrotizing pancreatitis

BackgroundThe MEHMO (mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity) syndrome, which is caused by a hemizygous variant in the EIF2S3 gene on chromosome Xp22, is associated with significant morbidity and mortality. Refractory epileptic seizures and glucose dysregulation are characteristic manifestations of the MEHMO syndrome, which can often diminish patients’ quality of life.CaseA 5-year-old boy was referred to our hospital because of profound intellectual disability, micropenis, cryptorchidism, central hypothyroidism, and microcephaly. He had neonatal hypoglycemia at birth and later experienced refractory epileptic seizures and developed obesity and insulin-dependent diabetes. A diagnosis of MEHMO syndrome was established on the basis of the patient’s clinical manifestations and de novo novel missense variant in the EIF2S3 gene (NM_001415.3:c.805 T > G) that was detected through whole-exome analysis. Although the patient’s refractory seizures and diabetes had been well controlled with a combination of ketogenic diet (KD) therapy and insulin therapy, acute fatal necrotizing pancreatitis occurred at the age of 68 months. Moreover, despite intensive care, his condition rapidly deteriorated to multiple organ failure and acute respiratory distress syndrome, resulting in death.ConclusionThe pathophysiology of glucose intolerance in MEHMO syndrome remains to be elucidated; however, recent studies have suggested that EIF2S3 gene variants could lead to glucose dysregulation and β-cell damage in the pancreas. We suspect that in the present case, KD therapy led to an abnormal load on the beta cells that were damaged owing to eIF2γ dysfunction. Therefore, the adverse effects of KD in patients with MEHMO syndrome should be considered.     

Development of pre and post-operative models to predict early recurrence of hepatocellular carcinoma after surgical resection

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Dissecting aneurysm during pregnancy and the puerperium

According to Schnitker, Mandel, Hirst and their associates, approximately half of the dissecting aneurysms in women under 40 years of age are associated with pregnancy. This significant relationship between dissecting aneurysm and pregnancy has been discussed by considering hemodynamic stress and also the hormonal changes of pregnancy. In this report, we describe five patients with dissecting aneurysm during pregnancy or the puerperium, review the literature and discuss the influence of pregnancy on the pathogenesis of this disease.     

Infection with hepatitis B virus genotype A in Tokyo, Japan during 1976 through 2001

Background Because genotype A of hepatitis B virus (HBV) is not indigenous, there have been only few data on infection with it in Japan.Methods We examined clinical and virological features of the 66 Japanese patients who admitted Toranomon Hospital in Tokyo, Japan, between 1976 and 2001, who were found to have HBV/A infection. HBV genotype A was classified into subtype A (European type) and A (South African type) by phylogenetic analysis of the preS1 and preS2 regions, and the S gene sequences.Results Of the 66 patients infected with HBV/A, 14 (21%) were asymptomatic carriers, 26 (39%) presented with acute hepatitis, 22 (33%) with chronic hepatitis, and 4 (6%) with liver cirrhosis. HBV/A infection persisted for more than 6 months in 5 of the 26 (19%) patients with acute hepatitis. The frequency of acute hepatitis in patients infected with HBV/A was higher after than before 1991 (2/22 [9%] vs 24/44 [55%]; P < 0.0001). The frequency of nucleotide 1858 of T was higher in asymptomatic carriers than in patients with acute hepatitis in whom infection was resolved (5/14 [36%] vs 0/21 [0%]; P = 0.008). Of the 57 patients for whom subtypes of genotype A were determined, subtype A was identified in 53 (93%) and subtype A in only 4 (7%). All patients infected with subtype A were persistently infected with HBV.Conclusions HBV/A infection has become more frequent during recent years, predominantly presenting as acute hepatitis, and subtype A is uncommon in the Tokyo metropolitan area.     

Evolution of the glutamine synthetase gene, one of the oldest existing and functioning genes.

We performed molecular phylogenetic analyses of glutamine synthetase (GS) genes in order to investigate their evolutionary history. The analyses were done on 30 DNA sequences of the GS gene which included both prokaryotes and eukaryotes. Two types of GS genes are known at present: the GSI gene found so far only in prokaryotes and the GSII gene found in both prokaryotes and eukaryotes. Our study has shown that the two types of GS gene were produced by a gene duplication which preceded, perhaps by > 1000 million years, the divergence of eukaryotes and prokaryotes. The results are consistent with the facts that (i) GS is a key enzyme of nitrogen metabolism found in all extant life forms and (ii) the oldest biological fossils date back 3800 million years. Thus, we suggest that GS genes are one of the oldest existing and functioning genes in the history of gene evolution and that GSI genes should also exist in eukaryotes. Furthermore, our study may stimulate investigation on the evolution of "preprokaryotes," by which we mean the organisms that existed during the era between the origin of life and the divergence of prokaryotes and eukaryotes.