Transient Elastography for the Prediction of Oxaliplatin-Associated Liver Injury in Colon Cancer Patients : A Preliminary Analysis

Objective

The prognosis of advanced colon cancer has improved significantly over the last decade since new chemotherapy regimens including oxaliplatin have been developed. However, oxaliplatin-induced liver injury and characterized hepatic hemostatic status can occur after chemotherapy. The assessment of this type of liver injury is often difficult.

Methods

Elastography (Fibroscan?) was used to evaluate liver injury in five cases before and after 5-FU, leucovorin, and oxaliplatin combination (FOLFOX) treatment.

Results

A clear change was observed in the stiffness of liver after chemotherapy within 48 h, and the hepatic stiffness was normalized in most cases after 2 weeks. Among the five patients, one patient showed aberrant elevation after a FOLFOX treatment, and the patient showed liver injury pathologically.

Conclusion

Elastography is a good tool for evaluating hepatic injury after FOLFOX treatment.     

Distribution of estimated glomerular filtration rate (eGFR) values in patients receiving contrast-enhanced magnetic resonance imaging

Purpose

The aim of this study was to elucidate the distribution of estimated glomerular filtration rate (eGFR) values in patients who underwent gadolinium-based contrast agent (GBCA)-enhanced magnetic resonance imaging (MRI) at different types of hospitals.

Materials and methods

We retrospectively studied 2,550 patients who underwent MRI at five institutions. We recorded the date and value of each patient??s eGFR test. The distribution of eGFR values was compared with that in the general Japanese population.

Results

A total of 84.3% of patients had their eGFRs evaluated before GBCA-enhanced MRI. Of these, 84.7% were evaluated within 3?months before the GBCA-enhanced MRI, and 1.3% were evaluated on the day of the GBCA-enhanced MRI. A total of 87.2% of patients tested had an eGFR of ??60?ml/min/1.73?m²; 12.8% had an eGFR of <60 and ??30?ml/min/1.73?m², and no patients had an eGFR of <30?ml/min/1.73?m².

Conclusion

The rate of renal function evaluation differed among hospitals. The prevalence of low eGFR values was greater in Juntendo Tokyo Koto Geriatric Medical Center than in the other hospitals, and the prevalence of low eGFR values was greater in patients who underwent GBCA-enhanced MRI than in the general Japanese population.     

Macrophage response to peripheral nerve injury: the quantitative contribution of resident and hematogenous macrophages

Whereas local microglial cells of the CNS rapidly respond to injury, little is known about the functional role of resident macrophages of the peripheral nervous system in nerve pathology. Using bone marrow chimeric rats, we recently identified individual resident endoneurial macrophages that rapidly became activated after nerve injury. However, the extent of local macrophage activation and its quantitative contribution to the total macrophage response is unknown. We now have created chimeric mice by transplanting bone marrow from green fluorescent protein (GFP)-transgenic mice into irradiated wild-type mice, allowing easy differentiation and quantification of hematogenous and resident endoneurial macrophages. After sciatic nerve crush injury, both GFP(-) and GFP(+) resident macrophages, the latter having undergone physiological turnover from the blood before injury, rapidly underwent morphological alterations and increased in number. Proliferating GFP(-) and GFP(+) resident macrophages were abundant and peaked 3 days after injury. A major lesion-induced influx of hematogenous macrophages with a disproportionate increase of GFP(+) macrophages was not observed until Day 4. Throughout all time points examined, GFP(-) resident macrophages were strikingly frequent, reaching maximum numbers 9.5-fold above baseline. There was also a notable proportion of GFP(-) resident endoneurial macrophages phagocytosing myelin and expressing major histocompatibility complex class II. Our results demonstrate for the first time that the rapid response of resident endoneurial macrophages to nerve injury is quantitatively important and that local macrophages contribute significantly to the total endoneurial macrophage pool during Wallerian degeneration.     

Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 3

The pathogenesis of hepatitis C virus (HCV)-associated insulin resistance remains unclear. Therefore, we investigated mechanisms for HCV-associated insulin resistance. Homeostasis model assessment for insulin resistance was increased in patients with HCV infection. An increase in fasting insulin levels was associated with the presence of serum HCV core, the severity of hepatic fibrosis and a decrease in expression of insulin receptor substrate (IRS) 1 and IRS2, central molecules of the insulin-signaling cascade, in patients with HCV infection. Down-regulation of IRS1 and IRS2 was also seen in HCV core-transgenic mice livers and HCV core-transfected human hepatoma cells. Carbobenzoxy-l-leucyl-l-leucyl-l-leucinal, a potent proteosomal proteolysis inhibitor, blocked down-regulation of IRS1 and IRS2 in HCV core-transfected hepatoma cells. In human hepatoma cells, HCV core up-regulated suppressor of cytokine signaling (SOCS) 3 and caused ubiquitination of IRS1 and IRS2. HCV core-induced down-regulation of IRS1 and IRS2 was not seen in SOCS3(-/-) mouse embryonic fibroblast cells. Furthermore, HCV core suppressed insulin-induced phosphorylation of p85 subunit of phosphatidylinositol 3-kinase and Akt, activation of 6-phosphofructo-2-kinase, and glucose uptake. In conclusion, HCV infection changes a subset of hepatic molecules regulating glucose metabolism. A possible mechanism is that HCV core-induced SOCS3 promotes proteosomal degradation of IRS1 and IRS2 through ubiquitination.     

Magnetic Resonance Imaging Grading System for Preoperative Diagnosis of Leiomyomas and Uterine Smooth Muscle Tumors

Study Objective

To evaluate a new magnetic resonance imaging (MRI) grading system for preoperative differentiation between benign and variant-type uterine leiomyomas including smooth muscle tumors of uncertain malignant potential (STUMPs).

Metabolomics analysis of umbilical cord blood clarifies changes in saccharides associated with delivery method

Background

A metabolomic approach using umbilical cord blood from infants at birth has not been studied widely yet.

Aim

We examined changes in metabolite levels in umbilical cord blood at birth via gas chromatography/mass spectrometry (GC/MS)-based metabolomics, with the aim of achieving a detailed understanding of fetal stress during labor.

Study design

All procedures were reviewed and approved by the Institutional Review Board of Kobe University School of Medicine. This was a cohort study of pregnant women based in Palmore Hospital, which is located in an urban area of Japan, and was carried out between December 2010 and May 2011.

Subject

Umbilical cord arterial blood samples were obtained from 41 infants immediately after delivery.

Outcome measures

Metabolites in the blood samples were measured using GC/MS to investigate whether the delivery method (spontaneous onset of labor, induction of labor or elective cesarean section) affected the metabolite profile in umbilical cord blood.

Results

Elective cesarean section without labor led to lower levels of isoleucine, fructose, mannose, glucose, allose, glucuronic acid, inositol and cysteine in comparison with vaginal delivery following spontaneous labor and without medication.

Conclusion

It is proposed that the stress associated with labor be involved in alterations in the levels of metabolites, particularly saccharides such as glucose, in umbilical cord blood.     

First Japanese case of Pierson syndrome with mutations in LAMB2

Pierson syndrome (OMIM 609049) is typically characterized by congenital nephritic syndrome and peculiar ocular anomalies with microcoria. It is caused by mutations in LAMB2, which encodes laminin β2. Approximately 50 mutations of LAMB2 from approximately 40 unrelated families have been identified; however, most of them were from Western countries. Although three patients in Asia with mutations of LAMB2 have been reported, they were not typical cases. We report the first Japanese case of Pierson syndrome with proven causative LAMB2 mutations. She presented with congenital nephrotic syndrome and bilateral microcoria at birth, and developed end‐stage renal disease at 2 months of age. This is the first report of a typical case from Asia. LAMB2 analysis by direct sequencing revealed the compound heterozygous mutations c.3974_3975insA (p.N1325KfsX1331, maternal, novel) in exon 25 and c.4519C>T (p.Q1507X, paternal) in exon 27. The phenotype due to LAMB2 mutations appears to be similar between different ethnic groups.     

Effects of methylprednisolone pulse on cytokine levels in Kawasaki disease patients unresponsive to intravenous immunoglobulin

This study aimed to determine the effects of intravenous methylprednisolone pulse (IVMP) therapy on cytokine levels in patients with acute Kawasaki disease (KD) unresponsive to initial intravenous immunoglobulin (IVIG) therapy. Fifteen KD patients unresponsive to initial IVIG, 2 g/kg/day, were randomized to receive IVMP (n = 7), 30 mg/kg/day for 3 days or additional IVIG (n = 8), 2 g/kg/day, and plasma cytokine levels were compared. The fraction of febrile patients was significantly lower in the IVMP group than in the additional IVIG group on day 2 (0/7 vs. 3/8, p = 0.03), but not on day 4 and later (3/7 vs. 4/8, p = 1.00) because of recurrent fever. The prevalence of coronary lesions was similar between the two groups (2/7 vs. 2/8, p = 1.00). The ratios of plasma levels of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 to those at enrollment (defined as day 1) were significantly lower in the IVMP group on day 4 (0.50 +/- 0.27 vs. 1.01 +/- 0.46, 0.53 +/- 0.39 vs. 0.93 +/- 0.44, p = 0.02 and 0.045, respectively), but not on day 7 (0.54 +/- 0.34 vs. 0.88 +/- 0.39, 0.76 +/- 0.39 vs. 0.61 +/- 0.17, p = 0.07 and 0.83, respectively). The ratios of interleukin-2 receptor, interleukin-6, and vascular endothelial cell growth factor to those at enrollment did not differ significantly between the two groups. In conclusion, for KD patients unresponsive to initial IVIG, IVMP suppresses cytokine levels faster, but subsequently similarly, compared with additional IVIG.