A case of neonate effectively treated with everolimus for giant hepatic hemangioma complicated with congenital duodenal atresia and Kasabach-Merritt syndrome.

BACKGROUND: Disseminated intravascular coagulation (DIC) with Kasabach-Merrit syndrome from a large hepatic hemangioma is life-threatening. We report a case of giant hepatic hemangioma of the newborn with KMS. RESULTS: The patient was born at 37 gestational weeks and 2 days via cesarean section; weight at birth was 2952 g. Congenital duodenal atresia was noted during the fetal period. DIC developed after delivery and a giant liver hemangioma was diagnosed via abdominal CT. The cause of DIC was Kasabach-Merritt syndrome owing to a giant hepatic hemangioma. First, combination therapy of 2 mg/kg/day of prednisolone and 0.2 mg/kg/day of propranolol was initiated form enterostomy. However, the size of the hepatic hemangioma did not alter, as observed via image evaluation. Therefore, 0.3 mg/kg/day of everolimus was administered frorm enterostomy. Subsequently, the size of the hepatic hemangioma was assessed via image evaluation. Although it did not alter, blood flow to the hepatic hemangioma decreased and thrombocytopenia was also suppressed. We performed hepatic lateral segmentectomy, radical operation for duodenal atresia. The pathological diagnosis of the removed tumor was infantile hemangioma. CONCLUSION: We report everolimus may be useful when PSL and propranolol are ineffective.

Mock-up experiment at Birmingham University for BNCT project of Osaka University--Neutron flux measurement with gold foil.

Mock-up experiment for development of accelerator based neutron source for Osaka University BNCT project was carried out at Birmingham University, UK. In this paper, spatial distribution of neutron flux intensity was evaluated by foil activation method. Validity of the design code system was confirmed by comparing measured gold foil activities with calculations. As a result, it was found that the epi-thermal neutron beam was well collimated by our neutron moderator assembly. Also, the design accuracy was evaluated to have less than 20% error.

Immunoglobulin prophylaxis against cytomegalovirus infection in patients at high risk of infection following allogeneic hematopoietic cell transplantation.

Reports on the efficacy of intravenous immunoglobulin (IVIG) prophylaxis against cytomegalovirus (CMV) infection after allogeneic hematopoietic cell transplantation (HCT) have often sparked controversy. In addition, we are not aware of any study that has examined whether prophylaxis with IVIG affects the incidence of CMV infection in high-risk patients--those who are elderly or have received human leukocyte antigen (HLA) mismatched HCT. In the present open-label, phase II study, we addressed this question. We enrolled 106 patients in the study. The cumulative incidences of CMV infection at 100 days after HCT were similar in the intervention and the control groups (68% and 64%, P=.89; 89% and 87%, P=.79, respectively, for patients 55 years or older and those who received HLA-mismatched HCT). In those who received HLA-mismatched HCT, 1-year overall survival after HCT was 46% in the intervention group and 40% in the control group (P=.31); for age≥55 years, the corresponding values were 46% and 40% (P=.27). Our data showed that prophylaxis with regular polyvalent IVIG did not affect the incidence of CMV infections or survival among older patients or those who receive HLA-mismatched HCT.

Accuracy and reliability of continuous blood glucose monitor in post-surgical patients.

BACKGROUND: The STG-22 is the only continuous blood glucose monitoring system currently available. The aim of this study is to determine the accuracy and reliability of the STG-22 for continuously monitoring blood glucose level in post-surgical patients. METHODS: Fifty patients scheduled for routine surgery were studied in surgical intensive care unit (ICU) of a university hospital. After admission to the ICU, the STG-22 was connected to the patients. An attending physician obtained blood samples from a radial arterial catheter. Blood glucose level was measured using the ABL800FLEX immediately after blood collection at 0, 4, 8, and 16 h post-admission to the ICU (total of 200 blood glucose values). RESULTS: The correlation coefficient (R2) was 0.96. In the Clarke error grid, 100% of the paired measurements were in the clinically acceptable zone A and B. The Bland and Altman analysis showed that bias+/-limits of agreement (percent error) were 0.04(0.7)+/-0.35(6.3) mmol (mg/dl) (7%), -0.11(-2)+/-1.22(22) (15%) and -0.33(-6)+/-1.28(23) (10%) in hypoglycemia (<70(3.89) mmol (mg/dl), normoglycemia (3.89(70)-10(180) mmol (mg/dl), and hyperglycemia (>10(180) mmol (mg/dl), respectively. CONCLUSIONS: The STG-22 can be used for measuring blood glucose level continuously and measurement results are consistent with intermittent measurement (percentage error within 15%). Therefore, the STG-22 is a useful device for monitoring in blood glucose level in the ICU for 16 h.

Bleeding time prolonged by daily low-dose aspirin is shortened by one medium dose aspirin.

BACKGROUND: In planning surgery, a low-dose aspirin regimen for prevention of thrombotic events is often discontinued in order to avoid the risk of excessive bleeding during surgery. However, this procedure increases the risk from adverse thrombotic events. We propose a different method, which may normalize the prolonged bleeding time caused by low-dose aspirin. We verified the effectiveness of this method in healthy volunteers. METHODS: Volunteers with bleeding time prolonged by taking 81 mg of aspirin a day for a period of 1 week were randomly divided into two groups. The test group of 18 volunteers received a dose of 660 mg of aspirin, while the control group of 16 received placebo. Bleeding time and maximum platelet activity were then evaluated. RESULTS: Before 660 mg of aspirin or placebo, bleeding time was prolonged: in the aspirin group from 3.1 +/- 0.7 to 6.1 +/- 1.4 min (n=18), and in the placebo group from 2.9 +/- 0.9 to 6.1 +/- 1.5 min (n=16). This prolongation was significant in both groups at the P<0.01 level. In the test group, bleeding time was shortened to 4.5 +/- 1.3 min (P<0.01), which is in the normal range, while it remained prolonged in the control group (6.0 +/- 1.2 min). Platelet activity, on the other hand, was suppressed in both groups. CONCLUSION: We conclude that 660 mg of aspirin effectively shortens the bleeding time prolonged by daily low-dose (81 mg) aspirin.

Saltiness enhancement by the characteristic flavor of dried bonito stock.

There is a pressing need for the development of ways of preparing palatable salt-reduced foods to reduce the salt intake of the Japanese population. The salt-reducing effect of the characteristic flavors other than umami of dried bonito stock, which is widely used in everyday Japanese food, was examined by sensory evaluation. In the 1st sensory evaluation, the effect was evaluated in a model solution. The saltiness of 0.80% NaCl solution was equivalent to that of 0.12% monosodium glutamate (MSG) solution containing 0.81% NaCl and dried bonito stock containing 0.68% NaCl. Saltiness enhancement could not be found when MSG solution was used, but was found with 6% dried bonito stock. The 2nd evaluation examined whether the effect was valid for 2 everyday Japanese foods--traditional Japanese clear soup (sumashi-jiru) and steamed egg custard (tamagodoufu). Although enhancement of saltiness by dried bonito stock could not be clearly demonstrated in the soup, a change in NaCl concentration within 15% did not affect the palatability of the soup. However, dried bonito stock not only enhanced the saltiness but also improved the palatability of steamed egg custard. These findings are expected to be useful for improving the palatability of salt-reduced food.

A review of studies and measures to improve the mycotoxicological safety of traditional Japanese mold-fermented foods.

Miso (fermented soybean paste), shoyu (soy sauce) and sake (rice wine) are traditional moldfermented foods in Japan and have been consumed throughout much of its history. These have long been considered safe foods. In this contribution we review and summarize long-term studies to investigate potential problems with mycotoxin contamination of these products. The fungal cultures used for fermentation of these products are called "koji-molds" and mainly consist of strains ofAspergillus oryzae. A. oryzae belongs to theA. flavus group taxonomically, which is generally known to be a main producer of aflatoxins. Therefore, we studied the productivity of aflatoxins by various koji-molds, as well as the possibility of aflatoxin contamination of rice (which is used in the production of fermented foods), miso, shoyu and sake. Rice was found to be free from aflatoxins. Furthermore, none of the tested koji-molds produced any detectable levels of aflatoxins, consequently no aflatoxins were found in miso, shoyu, or sake. However, some koji-molds are known to produce cyclopiazonic acid (CPA) and kojic acid (KA). We studied the production of CPA and KA by various commercial koji-molds and identified some strains that produce relatively high amounts of CPA or KA. Consequently, we advised food industry not to use these strains. Although mycotoxin contamination of these products is therefore presently very low, further attempts should be made to completely eliminate CPA and KA from fermented foods.

A human case of gnathostomiasis nipponica confirmed indirectly by finding infective larvae in leftover largemouth bass meat.

A human case of creeping eruption due to Gnathostoma nipponicum was confirmed indirectly by finding infective advanced third-stage larvae in leftover largemouth bass meat. This is the first report indicating that the largemouth bass (Micropterus salmoides) serves as a source of G. nipponicum infection in humans.

Hypercalcemic complication in patients with oral squamous cell carcinoma.

Hypercalcemia is one of the metabolic complications associated with cancer. To assess the frequency of hypercalcemia in patients with squamous cell carcinoma (SCC), 242 patients who were evaluated as having SCC in the oral cavity between July 1995 and June 2001 were investigated. All patients were periodically monitored for their serum level of calcium (Ca). Hypercalcemia was defined as a serum Ca concentration higher than 11 mg/dl. By this definition, hypercalcemia was detected in 12 of the 242 patients (5.0%). All 12 patients were at an advanced stage of oral SCC. In these 12 patients, the serum level of parathyroid hormone-related protein (PTH-rP) was also significantly elevated. Therefore, we diagnosed these diseases as humoral hypercalcemia of malignancy (HHM). Moreover, we studied the efficacy of anti-hypercalcemic therapy on the quality of life (QOL). The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 was used for estimation of QOL. The patients with HHM who were administrated drugs such as bisphosphonate and calcitonin showed a reduction in their Ca and PTH-rP levels, and the six of ten EORTC QLQ-C30 subscales (emotional functioning, cognitive functioning, fatigue, dyspnoea, nausea/vomiting and appetite loss) were also improved after the anti-hypercalcemic therapy. However, these suppressive effects were temporary. The median survival time after the diagnosis of HHM was only 54.9+/-18.3 days (range 27-86 days). Therefore, HHM in SCC appears to be an ominous prognostic sign. Although anti-hypercalcemic therapy has a palliative role, the patients may be in less discomfort during the terminal stage of their illness.

Effect of three flavonoids, 5,7,3',4'-tetrahydroxy-3-methoxy flavone, luteolin, and quercetin, on the stimulus-induced superoxide generation and tyrosyl phosphorylation of proteins in human neutrophil.

The effect of three flavonoids, 5,7,3',4'-tetrahydoxy-3-methoxy flavone (THMF), luteolin, and quercetin, on the stimulus-induced superoxide generation and tyrosyl phosphorylation of proteins in human neutrophils were investigated. When the cells were preincubated with these flavonoids, the superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was significantly suppressed, showing a dependence on amounts of the flavonoid. The suppressing effect of the flavonoid was THMF > luteolin > quercetin. These flavonoids also suppressed the superoxide generation induced by phorbol 12-myristate 13-acetate. In this case also, THMF was more effective than luteolin and quercetin. On the other hand, the superoxide generation induced by arachidonic acid was markedly suppressed by quercetin. The suppressing effect was quercetin >> THMF > luteolin. THMF, luteolin, and quercetin significantly suppressed tyrosyl phosphorylation of 80.1-, 58.0-, and 45.0-kDa proteins in fMLP-treated human neutrophils. The suppression depended on the concentration of the flavonoids, and the inhibition of tyrosyl phosphorylation was in parallel to that of the fMLP-induced superoxide generation, respectively. While luteolin and quercetin showed a weak hemolytic activity at 2.5 mM, THMF showed almost no hemolytic activity even at 5 mM, suggesting an advantage of THMF for its clinical use.

Homozygosity mapping to chromosome 5p15 of a gene responsible for Hartnup disorder.

Hartnup disorder is an autosomal recessive phenotype involving a transporter for monoamino-monocarboxylic acids. Genetic analysis of the mouse model mapped its locus to human chromosome 11q13 (8). We report here the results of linkage analysis in two Japanese first cousin-marriage families. In the first family, the proband had Hartnup disorder and his deceased older brother was reported to have had typical Hartnup symptoms. The younger brother of the proband was shown to have decreased tryptophan absorption by oral loading test. In the second family, a 6-year-old girl, the proband, had specific hyperaminoaciduria. DNA was isolated from either blood samples or umbilical cord stumps. Genome-wide screening by homozygosity mapping was conducted. Taking into account that the older brother was affected and the younger brother was a carrier in the first family, homozygosity mapping (LOD score = 3.55) and GENEHUNTER (LOD score = 3.28) locates the locus of the Hartnup disorder on 5p15.

Relationship between triglyceride concentrations and LDL size evaluated by malondialdehyde-modified LDL.

BACKGROUND: Hypertriglyceridemia is associated with decreased HDL-cholesterol (HDL-C) and increased small dense LDL. In addition, small dense LDL is known to be susceptible to oxidation. METHODS: We measured LDL particle size, using gradient gel electrophoresis, and malondialdehyde-modified LDL (MDA-LDL), using an ELISA, and investigated the association between triglyceride (TG) concentrations, LDL size, and MDA-LDL. RESULTS: TG concentrations correlated negatively with the predominant LDL size (r = -0.650) and HDL-C concentration (r = -0.556). The relationship between TG concentration and LDL size, evaluated by measuring MDA-LDL, distinguished subgroups derived from four subfractions of TG concentrations and four distribution ranges of LDL size. These experiments indicated that there is a threshold for oxidation susceptibility at an LDL size of 25.5 nm and a TG concentration of 1500 mg/L. To investigate the relationship between LDL size, MDA-LDL concentration, and other lipids (TGs, HDL-C, apolipoprotein B, and total cholesterol), we evaluated them in control subjects and patients with diabetes mellitus or hypertriglyceridemia. When the size range for normal LDL was postulated to be 25.5 < or = phi (LDL diameter) < 26.5 nm, the MDA-LDL concentration was significantly higher in the subgroups of patients with LDL in the size range 24.5 < or = phi < 25.5 nm compared with patients with normal LDL. This result also suggests that the threshold is at a LDL size of 25.5 nm. CONCLUSION: The threshold for oxidation susceptibility coincided with the point of LDL size separation between the LDL subclass patterns A and B as an atherosclerotic risk.

An in vitro approach to the evaluation of the cross talk between intestinal epithelium and macrophages.

The intestinal epithelium acts as a mucosal barrier by varying their signals to immune cells within the intestine. To observe the cross talk between intestinal epithelium and macrophages, we establish a Caco-2-THP-1 co-culture system. Using this co-culture system, we suggested that paracrine factors of intestinal epithelium increased the phagocytic capacity of intestinal monocytes/macrophages to be ready for immune and inflammatory responses.

[Epidural anesthesia for a patient with catamenial pneumothorax].

Endometriosis extending into the thoracic cage or the lung might induce defect of the tissue and show catamenial symptoms, such as pneumothorax or hemothorax. These events usually occur 48 to 72 hours after menstruation. A 37-year-old woman with ten year history of recurrent catamenial pneumothorax was scheduled for removal of ovarian cyst. Since intermittent positive pressure ventilation or pneumoperitoneum might induce pneumothorax, we selected epidural anesthesia for laparotomy. Epidural cannulations were performed at Th 9/10 and L 4/5 interspaces. After administration of 2% mepivacaine (400 mg) and fentanyl (0.1 mg), the block extended from Th 6 to S 5. The surgery was done without any complication. In this case epidural anesthesia for laparotomy was useful for the patient with catamenial pneumothorax.

Spontaneous regression of merkel cell carcinoma: a comparative study of TUNEL index and tumor-infiltrating lymphocytes between spontaneous regression and non-regression group.

Some Merkel cell carcinomas (MCC) have been reported to regress spontaneously. To clarify the mechanisms of spontaneous regression (SR) of MCC, we analyzed the TUNEL index, the labeling index of proliferating cell nuclear antigen (PCNA), the labeling index of bcl-2 protein, and the expression of p53 of the tumor cells. We also evaluated the number of infiltrating lymphocytes surrounding the tumor in the tissue specimens. Among seven patients with MCC (SR: n=4; non-regression (NR): n=3), the TUNEL index in the SR group was significantly higher than that in NR group (5.2 and 2.0%, respectively). In addition, the number of lymphocytes around the tumor nests was also significantly increased in the SR group compared to NR group (1576 and 663 cells/mm(2), respectively). Most of the infiltrating lymphocytes were UCHL-1 positive T-cells. There were no significant differences of the PCNA labeling index, the bcl-2 protein labeling index, and the expression p53 between SR and NR group. These results indicate that apoptosis and local T-cell mediated immune response might be involved in spontaneous regression of MCC.

Human peptidylarginine deiminase type III: molecular cloning and nucleotide sequence of the cDNA, properties of the recombinant enzyme, and immunohistochemical localization in human skin.

Peptidylarginine deiminase catalyzes the post-translational modification of proteins through the conversion of arginine to citrulline in the presence of calcium ions. In rodents, peptidylarginine deiminase has been classified into four isoforms, types I, II, III, and IV, which are distinct in their molecular weights, substrate specificities, and tissue localization. Of these isoforms, only type III was detected in epidermis and hair follicles. Although the role of this enzyme in these tissues is not yet clear, indirect data have shown that several structural proteins such as filaggrin, trichohyalin, and keratin are substrates for peptidylarginine deiminase. In this study, we cloned the full-length cDNA of human peptidylarginine deiminase type III (3142 bp) from cultured human keratinocytes by reverse transcription-polymerase chain reaction and by rapid amplification of cDNA ends methods. This cDNA contained a 1995 bp open reading frame encoding 664 amino acids (Mr = 74 770). To explore the physicochemical and enzymatic properties of human peptidylarginine deiminase type III, we constructed a plasmid for producing a recombinant human peptidylarginine deiminase type III in bacteria. The enzymatic characteristics of the recombinant enzyme were very similar to those of the rodent peptidylarginine deiminase type III. The recombinant enzyme showed the catalytic activities toward structural proteins of epidermis and hair follicle, filaggrin and trichohyalin, in which the deiminations maxima of about 60% and 13% arginine residues were observed in filaggrin and trichohyalin, respectively. An immunohistochemical study of human scalp skin with a monospecific anti-peptidyl-arginine deiminase type III antibody revealed that the type III enzyme was localized to the inner root sheath and outer root sheath of hair follicles. Peptidylarginine deiminase type III in the inner root sheath was notable between supramatrix and keratogenous zone and was scarcely detected in cornified hair zone. The enzyme was also expressed in the cuticle layer of hair. On the other hand, expression of the enzyme in the epidermis was very low. These data imply that human peptidylarginine deiminase type III is the predominant isoform in hair follicles and may function as a modulator of hair structural proteins, including trichohyalin during hair and hair follicle formation.