Clinical significance of proteinuria determined with dipstick test,edema, and weekly weight gain ⩾500 g at antenatal visit

ObjectiveTo determine how urine dipstick test, edema, and/or excessive weight gain (EWG, defined as ?500 g/week) at antenatal visits predict significant proteinuria (defined as a protein-to-creatinine ratio [P/Cr, mg/mg] ?0.27) and preeclampsia.MethodsData from 3279 antenatal visits between 30 and 36 weeks of gestation were studied in 783 women with singleton pregnancies. In 24 preeclamptic pregnancies, data from 89 antenatal visits at and before diagnosis of preeclampsia were used. Spot P/Cr was determined in women with repeated positive dipstick test results in two successive antenatal visits or in those with a positive dipstick test result tested in the presence of hypertension.ResultsProteinuria on dipstick test, edema, and EWG appeared often in both women with and without preeclampsia; 66.7% vs. 27.7%, 83.3% vs. 44.1%, and 91.7% vs. 81.6%, respectively. However, repeated positive dipstick test results in two successive antenatal visits yielded sensitivity of 45.5%, specificity of 95.2%, and positive and negative predictive values of 30.0% and 97.4%, respectively, for detection of significant proteinuria and corresponding figures of 33.3%, 94.1%, 14.0%, and 98.0% for prediction of preeclampsia.ConclusionRepeated positive dipstick test results in two successive antenatal visits warrant a need for a confirmation test of significant proteinuria.     

Phenotypic Changes in Macrophage Activation in a Model of Nonalcoholic Fatty Liver Disease using Microminipigs

Aim: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders associated with metabolic syndrome, and its prevalence has been on the rise. The pathogenesis of NAFLD has not yet been sufficiently elucidated due to the multifactorial nature of the disease, although the activation of macrophages/Kupffer cells is considered to be involved. We previously reported an animal model of NAFLD using Microminipigs ^TM (µMPs) fed high-fat diets containing cholesterol with or without cholic acid. The aim of this study was to investigate the phenotypic changes of macrophages that occur during the development of NAFLD. Methods: Immunohistochemistry of macrophages, lymphocytes, and stellate cells was performed using liver samples, and the density of positive cells was analyzed. Results: The number of Iba-1-positive macrophages increased with increasing cholesterol content in the diet. The numbers of CD163-positive macrophages and CD204-positive macrophages also increased with increasing cholesterol content in the diet; however, the proportion of CD204-positive macrophages among Iba-1-positive macrophages was significantly reduced by cholic acid supplementation. Conclusion: The results suggest that lipid accumulation induced macrophage recruitment in swine livers, and that the number of M2-like macrophages increased at the early stage of NAFLD, while the number of M1-like macrophages increased at the late stage of NAFLD, resulting in a liver condition like non-alcoholic steatohepatitis. We provide evidence of the phenotypic changes that occur in macrophages during the development of NAFLD that has never been reported before using µMPs.     

Localization of tumour necrosis factor-alpha converting enzyme in normal human skin

The tumour necrosis factor (TNF)-alpha converting enzyme (TACE) is a metalloproteinase-disintegrin that releases soluble TNF-alpha from cells by cleaving within the extracellular domain of membrane-bound pro-TNF-alpha. TACE knockout mice display a range of epithelial abnormalities. However, the localization of TACE in normal human skin is unclear. In this study, we examined the expression of TACE in normal skin by immunohistochemical analysis. The expression of TACE was seen throughout all layers of the epidermis, the hair follicles, eccrine ducts and glands, and sebaceous glands. There was also staining of blood vessels in the dermis. In particular, TACE was localized predominantly in mast cells, suggesting that these cells are an important source of TNF-alpha.     

A case of subcorneal pustular dermatosis treated with tacalcitol (1alpha,24-dihydroxyvitamin D3)

We report a case of subcorneal pustular dermatosis (SPD) treated with tacalcitol (1alpha,24-Dihydroxyvitamin D3) ointment. A 77-year-old male had had asymptomatic, superficial, grouped pustules in annular patterns with mild background erythema for six years which affected his axillae and bilateral groin. A diagnosis of SPD was made. Topical vitamin D3 (tacalcitol) was applied to the lesion of SPD and its clinical effectiveness was assessed. Within one month, symptoms in the lesion treated with tacalcitol ointment started subsiding, and eventually only erythema remained. After three months, the region treated with tacalcitol ointment showed no relapse. We conclude that tacalcitol ointment is effective for SPD in some case.     

Dermatomyositis and pregnancy. Case report and review of the literature.

Dermatomyositis is a rare disease complicating pregnancy. We treated a patient in whom two pregnancies were complicated by dermatomyositis. In the first of the two gestations, a mild form of the disease arose in the last trimester. In the second gestation, the disease was inactive following treatment with 0.3 mg/kg/day prednisolone. Both the mother and two children have since been doing well.     

Plasma microRNA profiles: identification of miR-25 as a novel diagnostic and monitoring biomarker in oesophageal squamous cell carcinoma

Background:

Recent studies have demonstrated that microRNAs are stably detectable in plasma/serum because of their binding to specific proteins or being packaged in secretory particles. This study was designed to detect novel microRNAs in plasma for cancer detection and monitoring using microRNA array-based approaches in oesophageal squamous cell carcinoma (ESCC) patients.

Methods:

Through the integration of two Toray 3D-Gene microRNA array-based approaches to compare plasma microRNA levels between ESCC patients and healthy volunteers and between preoperative and postoperative ESCC patients, we identified a novel plasma biomarker in ESCC.

Results:

(1) Eight upregulated and common microRNAs (miR-15b, 16, 17, 25, 19b, 20a, 20b, and 106a) were selected using two high-resolution microRNA array approaches. (2) Test-scale analyses by quantitative RT–PCR validated a significant higher levels of plasma miR-19b (P=0.0020) and miR-25 (P=0.0030) in ESCC patients than controls. However, a significant correlation was observed between plasma miR-19b levels and concentrations of red blood cells (P=0.0073) and haemoglobin (P=0.0072). (3) miR-25 expression was found to be significantly higher in ESCC tissues (P=0.0157) and ESCC cell lines (P=0.0093) than in normal tissues and fibroblasts. (4) In a large-scale validation analysis, plasma miR-25 levels were significantly higher in 105 preoperative (P<0.0001) ESCC patients who underwent curative oesophagectomy and 20 superficial ESCC patients who underwent endoscopic resection (P<0.0001) than in 50 healthy volunteers. (5) Plasma miR-25 levels were significantly reduced in postoperative samples than in preoperative samples (P<0.0005) and were significantly increased during ESCC recurrences (P=0.0145).

Conclusions:

Plasma miR-25 might be a clinically useful biomarker for cancer detection and the monitoring of tumour dynamics in ESCC patients.     

Molecular analysis of the BCR-ABL1 kinase domain in chronic-phase chronic myelogenous leukemia treated with tyrosine kinase inhibitors in practice: Study by the Nagasaki CML Study Group

An appropriate trigger for BCR-ABL1 mutation analysis has not yet been established in unselected cohorts of chronic-phase chronic myelogenous leukemia patients. We examined 92 patients after 12 months of tyrosine kinase inhibitor (TKI) treatment in Nagasaki Prefecture, Japan. Univariate analysis revealed that significant factors associated with not attaining a major molecular response (MMR) were the presence of the minor BCR-ABL1 fusion gene, a low daily dose of TKI, and the emergence of BCR-ABL1 kinase domain mutations conferring resistance to imatinib. Factors associated with the loss of sustained MMR were a low daily dose of TKI and the emergence of alternatively spliced BCR-ABL1 mRNA with a 35-nucleotide insertion. Taken together, our results suggest that the search for BCR-ABL1 mutations should be initiated if patients have not achieved MMR following 12 months of TKI treatment.     

Differential relationship between changes in tumour size and microcirculatory functions induced by therapy with an antivascular drug and with cytotoxic drugs. implications for the evaluation of therapeutic efficacy of AC7700 (AVE8062)

A novel combretastatin A-4 derivative, AC7700, which is now in Phase I clinical trials under a new code, AVE8062, has shown strong antitumour effects against solid tumours in rodents because of its powerful and continued stanching of the tumour blood flow (TBF). Despite the strong tumour-suppressing qualities of AC7700, it does not produce an immediate reduction in tumour size. To elucidate the reason for this effect, we investigated the relationship between the change in tumour size in Sato lung carcinoma (SLC) and circulatory functions after therapy with AC7700, doxorubicin (Adriamycin [ADR]), or mitomycin C (MMC). To measure time-lapse changes in TBF with the hydrogen clearance method at the same site after drug administration, we developed a new apparatus for keeping electrodes within a tumour. AC7700 led to the destruction of both cancer cells and tumour vessels by interrupting the supply of nutrients. Intravenous (i.v.) administration of fluorescent dyes after AC7700 treatment revealed no fluorescence within the tumour vessels, which confirmed that the tumour microcirculation had been completely blocked. In contrast, ADR led to the destruction of SLC tumour cells, but did not have the same effect on tumour vessels. Intravenously administered fluorescent dyes immediately reached the tumour, which indicated that the tumour vasculature remained intact, and the TBF remained at the preadministration level, even 6 days after ADR treatment. In addition, although the size of the tumour increased slightly for 2 days with ADR treatment, possibly because of swelling of the cancer cells, thereafter it continued to decrease. MMC had virtually no effect on SLC tumour cells, tumour size or tumour vessels. We conclude that changes in tumour size brought about by cancer chemotherapy depend not only on the sensitivity of the cancer cells to the drug in question, but also on the nature of changes in the microcirculatory functions of the tumour brought about by the therapy. When both tumour cells and the tumour vasculature are destroyed, the effectiveness of therapy can not be determined from changes in tumour size alone.     

Intra-arterial CT-angiography for cerebral arteriovenous malformation--initial experiences for treatment planning of radiosurgery

PURPOSE: To clarify the feasibility and effectiveness of intra-arterial CT angiography (IACTA) for treatment planning of arteriovenous malformation radiosurgery. METHODS AND MATERIALS: A CT scanner installed in an angiographic examination room was used. Helical IACTA was performed in 22 patients during continuous intra-arterial infusion of contrast medium via the internal carotid or vertebral artery, and dynamic IACTA was performed in 20 of these patients with reconstruction at 0.2-s intervals. The dynamic IACTA was repeated for each 3- or 5-mm increment to encompass the nidus. Subtractions were performed in postembolization cases. A retrospective review of IACTA was performed to assess the effectiveness of dynamic scans. RESULTS: No complications related to the angiographic procedure or CT imaging were detected. High contrast enhancement was obtained for both helical and dynamic IACTA. In 18 of the 20 cases (90%), draining veins were separated from the nidus by using the enhancement patterns, and in 13 cases (65%), feeding arteries were separated. CONCLUSION: Dynamic IACTA added important information for target-volume determinations. Conventional CT and MRI could be omitted from the protocol, and the period that patients wore the frame was substantially shortened. We conclude that IACTA is a practical and useful method for radiosurgical treatment planning of arteriovenous malformations.