Fenofibrate increases high molecular weight adiponectin in subjects with hypertriglyceridemia

Beneficial effects of peroxisome proliferator-activated receptor alpha (PPAR alpha) agonists have been reported in improving insulin sensitivity and raising serum total adiponectin. High molecular weight (HMW) adiponectin, which is secreted from adipocytes, and visfatin, which is also expressed in adipose tissue, is related to glucose metabolism. In view of the additive effects of PPAR alpha agonists on these adipocytokines and glucose metabolism, we investigated male hypertriglyceridemic subjects who were treated with fenofibrate. Eleven male subjects with hypertriglyceridemia were treated with fenofibrate and serum total cholesterol (T-cho), triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting glucose, fasting insulin, total and HMW adiponectin, and serum visfatin levels were determined before and 3 months after treatment. Fenofibrate treatment significantly lowered T-cho, triglyceride, and LDL-C levels. There was a statistically significant increase of HDL-C. No differences in insulin sensitivity indices (G/I ratio and HOMA-IR) were observed between before and after treatment with fenofibrate. The treatment did not alter the levels of serum total adiponectin and visfatin in the hypertriglyceridemic patients, while serum HMW adiponectin increased significantly. This study demonstrates that fenofibrate increases serum HMW adiponectin levels, whereas visfatin is not regulated by fenofibrate in hypertriglyceridemic subjects. Further investigations are warranted to determine whether the elevation of HMW adiponectin caused by fenofibrate might improve insulin sensitivity.     

Vitamin K deficiency bleeding with intracranial hemorrhage: focus on secondary form

Non-accidental trauma is the leading cause of intracranial hemorrhage (ICH) in infancy. In contrast, ICH as a part of vitamin K deficiency bleeding (VKDB) secondary to hepatobiliary disease is rare, but encountered even in the era of vitamin K (VK) prophylaxis. During 43 months, six cases with ICH were diagnosed as an initial presentation of VKDB. Clinical features and imaging findings of them were retrospectively reviewed. All cases were breastfed and received oral VK prophylaxis. Liver dysfunction was found in five. Brain CT showed hemorrhage in subdural and subarachnoid space in six, parenchyma in three, and ventricle in one. Abdominal ultrasound was positive in four with final diagnoses of biliary atresia in two, neonatal hepatitis in one, and milk allergy in one. Two cases with negative ultrasound were diagnosed as idiopathic VKDB. In conclusion, ICH with secondary VKDB is rare, but important in infancy in the era of VK prophylaxis.     

Heritability of Serum Apolipoprotein Concentrations in Middle-Aged Japanese Twins

Background

Studies of the genetic and environmental influences on apolipoproteins have been conducted, but few have used data from Japanese twins. The aim of this study was to quantify and compare the genetic and environmental causes of individual differences in the serum concentrations of apolipoproteins in Japanese middle-aged twins.

Methods

Apo A-I, apo A-II, apo B, apo C-II, apo C-III, and apo E were studied. A total of 142 twin pairs, aged 45 through 65 years, were enrolled: 85 monozygotic pairs (59 male, 26 female) and 57 same-sexed dizygotic pairs (43 male, 14 female). The intraclass correlation coefficient and structural equation modeling were used to estimate the best-fitting model and heritability.

Results

Sixteen percent to 75% of the total variances of apo A-I, apo C-II, and apo C-III were attributable to genetic influence; apo A-I and apo C-II were influenced by dominant genetic factors. Twenty percent to 73% of the total variances of apo A-II, apo B, and apo E were attributable to additive genetic influence; apo B was clearly influenced by common environmental factors. Furthermore, the heritability of all apolipoproteins was higher among females than among males.

Conclusions

Genetic factors, including additive genetic effects (A) and dominant effects (D), influence apolipoprotein levels. However, a common environment does not influence the variances of these apolipoproteins, with the exception of apo B. Furthermore, the heritability of apolipoprotein phenotypes differs by sex.Key words: apolipoprotein, heritability, adult twins     

Granulosa cell tumor associated with secondary amenorrhea and serum luteinizing hormone elevation

Adult granulosa cell tumors (GCTs) are the most common type of ovarian sex cord tumors. Menstrual irregularity, menorrhagia, or even secondary amenorrhea is frequently observed in premenopausal women bearing GCTs with hormonal activity. We report herein a case of GCT in a patient presenting with secondary amenorrhea and serum luteinizing hormone elevation. A 28-year-old primigravid Japanese woman was admitted complaining of secondary amenorrhea of 2 years' duration. Pelvic examination, transvaginal ultrasonography, and magnetic resonance imaging demonstrated a left ovarian tumor 4 cm in diameter. Serum hormone assays revealed a follicle-stimulating hormone level of 4.8 mIU/ml, luteinizing hormone (LH) of 35.8 mIU/ml, estradiol of 24 pg/ml, progesterone of 1.6 ng/ml, and testosterone of 40 ng/dl. A left salpingo-oophorectomy was performed. The tumor was diagnosed as an adult-type GCT stage IIb (FIGO [International Federation of Obstetricians and Gynecologists], 1988). Spontaneous menstruation occurred soon after the surgery. Serum levels of LH also decreased to normal levels and showed cyclic changes during the menstrual cycle. Subsequently, the patient conceived and delivered a healthy female baby. The tumor recurred in the pelvis 50 months after the initial conservative surgery, with elevated serum LH levels of 36.0 mIU/ml and amenorrhea. The patient was treated by hysterectomy, right salpingo-oophorectomy, omentectomy, paraaortic and pelvic lymphadenectomy, and low anterior resection of the recto-sigmoid colon. Her hormone levels progressed to the postmenopausal state after this surgery. Although LH elevation in patients with GCT is rare and its mechanism is unknown, monitoring of serum LH may provide an additional tumor marker after conservative surgery in such patients.     

A case of elderly metastatic breast cancer with a complete response to treatment with capecitabine and cyclophosphamide

We report a case of elderly metastatic breast cancer with a complete response to the treatment with XC (X: capecitabine and C: cyclophosphamide). A 78-year-old woman, who presented with left breast cancer, underwent pectoralis-preserving mastectomy when she was 76 years old. Pathological findings were as follows: invasive ductal carcinoma (scirrhous type), pT1c (2.0 cm), n (1/10), ly3, v1, ER (-), PgR (-), HER2: score 1. After one year and a half, a left supraclavicular lymph node metastasis, a left interpectoral lymph node metastasis, and mediastinal lymph nodes metastasis were noted. Capecitabine and cyclophosphamide were administered as first-line chemotherapy. After 8 cycles, all metastases responded, and this therapy is now being continued (19 cycles) on an outpatient basis. The complete response has continued for nine months. XC therapy can be the first-line chemotherapy for elderly metastatic breast cancer patients since it has been effective and no serious side effects have been encountered while maintaining quality of life.     

Atypically enhanced cavernous hemangiomas of the liver: centrifugal enhancement does not preclude the diagnosis of hepatic hemangioma

The imaging features of an atypically enhanced hepatic hemangioma have not been well described in the literature, and the presence of such atypia may sometimes cause clinical problems in the differential diagnosis. Herein, we report a case of hepatic hemangioma demonstrating a previously unreported atypical enhancement pattern. On dynamic computed tomography during hepatic arteriography, a centrifugal enhancement pattern and subsequent peritumoral ring-shaped enhancement mimicking corona enhancement were found in cavernous hemangiomas of the liver in a 68-year-old Japanese man. Histopathological diagnosis of cavernous hemangioma of the liver was made on a biopsy specimen. Considering the importance of differentiating benign hepatic tumor from various forms of malignancy, radiologists and hepatologists should be aware of rare enhancement patterns sometimes seen in hepatic hemangioma. Establishing knowledge of the entire spectrum of atypical hepatic hemangioma may benefit the rational approach to future cases.     

Living-donor liver transplantation for carbamoyl phosphate synthetase 1 deficiency

CPS1 is a mitochondrial matrix enzyme that catalyzes the first committed step of the urea cycle, the primary system for removing nitrogen produced by protein metabolism using N-acetylglutamate. Patients with CPS1 deficiency have severe hyperammonemia that results in serious neurologic sequelae and sometimes death. LT has been indicated for neonatal-onset CPS1 deficiency. This study retrospectively reviewed five children with a diagnosis of CPS1 deficiency who underwent LDLT from heterozygous donors. Between November 2005 and May 2010, 124 children underwent LDLT with an overall patient and graft survival of 91.0%. Five patients were indicated for LDLT because of CPS1 deficiency. All recipients achieved resolution of their metabolic derangement, without donor complication, with a normal feeding regimen without medication for their original metabolic liver disease. LDLT, even from heterozygous donors, appears to be a feasible option, associated with a better quality of life for treating patients with CPS1 deficiency. Long-term observation may therefore be necessary to collect sufficient data to confirm the efficacy of this treatment modality.     

A Phase II Study of VEPA/FEPP Chemotherapy for Aggressive Lymphoma in Elderly Patients: Japan Clinical Oncology Group Study JCOG9203

The Lymphoma Study Group (LSG) of the Japan Clinical Oncology Group conducted a phase II trial of LSG12 therapy for 45 elderly patients with aggressive lymphoma to clarify whether LSG12 reduces severe infection without lowering the complete response (CR) rate in comparison with LSG4. LSG12, which consisted of a regimen of vincristine, cyclophosphamide, prednisolone, doxorubicin, vindesine, etoposide, and procarbazine (VEPA/FEPP), excluded bleomycin and methotrexate of LSG4 therapy, reduced the dosages of doxorubicin and cyclophosphamide, and increased etoposide and procarbazine dosages instead. Inclusion criteria consisted of a patient age of 70 to 75 years, a World Health Organization performance status of 0 to 2, and acceptable organ function.The treatment was completed in 47% of the patients and terminated early for disease progression in 20% and for toxicity in 16%.The CR rate was 60% (95% confidence interval [CI], 44%-74%).The 5-year overall survival (OS) rate was 42% (95% CI, 27%-57%), and the median OS time was 4.3 years. Leukopenia of grade 3 to 4 occurred in 98% of the patients, and severe infection occurred in 9%. Eight patients with hepatitis C virus (HCV) antibody showed no severe hepatic toxicity and had a better CR or OS rate than the 37 HCV-negative patients. Although the outcomes of LSG12 met our expectations with a reduction in severe infection and equivalent CR and OS outcomes compared with LSG4 and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), the possibility of a regimen more beneficial than LSG12 for aggressive lymphoma in the elderly patient should be explored because of frequent hematologic toxicity and poor compliance in LSG12.     

Emergence of H274Y oseltamivir-resistant A(H1N1) influenza viruses in Japan during the 2008–2009 season

BackgroundA substantial increase in oseltamivir-resistant A(H1N1) influenza viruses was reported in Europe in late 2007.ObjectivesTo monitor the antiviral susceptibility profile of human A(H1N1) influenza viruses in Japan during the 2007–2008 and 2008–2009 seasons.Study designViruses were obtained from respiratory samples of patients with influenza collected in Japan between December 2007 and April 2008 (n = 1046) and between December 2008 and April 2009 (n = 1789). Oseltamivir resistance was determined by an H274Y-specific real-time PCR cycling probe assay and a neuraminidase inhibition assay. Amantadine resistance was assessed by sequencing the M2 gene. Sequencing of the hemagglutinin and NA genes was performed to infer phylogenetic relationships between different strains.ResultsThree of 687 (0.4%) A(H1N1) viruses from the 2007–2008 season and 745 of 745 (100%) viruses from the 2008–2009 season carried the NA–H274Y substitution and demonstrated a >300-fold reduction in oseltamivir susceptibility. All oseltamivir-resistant viruses from the 2008–2009 season possessed an A193T substitution in the receptor-binding domain of the hemagglutinin. Amantadine resistance was detected in 431 of 687 (62.7%) and 0 of 745 (0.0%) of the A(H1N1) viruses from the 2007–2008 and 2008–2009 seasons, respectively.ConclusionsA dramatic surge in oseltamivir-resistant A(H1N1) viruses possessing the NA–H274Y substitution was detected in Japan during the 2008–2009 season. The emergence of oseltamivir-resistant viruses was facilitated by mutations in the viral genome. Intensified surveillance, including phenotypic assays and sequencing of the hemagglutinin, neuraminidase, and M2 gene would allow monitoring of the spread and evolution of drug-resistant influenza virus variants.