Biclonal Extramedullary Plasmacytoma Arising in the Peritoneal Cavity: Report of a Case

We report a rare case of extramedullary plasmacytoma, which arose either in the ileum or the ileal mesentery. A 70-year-old woman presented with a high fever and symptoms of bowel obstruction. Computed tomography and magnetic resonance imaging showed a large heterogeneous tumor in the peritoneal cavity. Serum immunoelectrophoresis revealed a biclonal increase of IgA- and IgG-. At surgery, we found that the parenchyma of the fragile tumor had firm communication with the ileal mesentery, and the cavity of the tumor communicated with the ileal lumen. After a temporary regression following surgery and chemotherapy, the tumor grew rapidly. Although there was no evidence of progression to multiple myeloma, the patient died of cachexia less than 4 months after surgery.     

The beneficial effect of effective control of anemia on hyperinsulinemia and hypoxemia in a hemodialysis patient with corrected transposition of the great arteries

We report the beneficial effect of control of anemia on hyperinsulinemia and hypoxemia in a hemodialysis patient with corrected transposition of the great arteries. The patients hemoglobin (Hb) level of 10.3g/dl on admission represents good control for hemodialysis (HD) patients, but it was too low for this patient with secondary polycythemia because of a right-to-left shunt. Control of anemia for a 10-month period was followed by a marked increase in Hb level (from 10.3g/dl to 13.9g/dl) and in aerobic work capacity, while the fasted insulin level decreased from 36.7µU/ml to 8.0µU/ml, without changes in leptin level, body mass index (BMI), fat mass, Kt/V, or protein catabolic rate (PCR). Additionally, hypoxemia was ameliorated, from PO₂ 33.1mmHg to PO₂ 56.2mmHg, and the hyperdynamic cardiac state was improved. The degree of anemia, together with deteriorating tissue oxygenation, may have predisposed this patient to developing insulin resistance and consequent hyperinsulinemia. The most appropriate target Hb concentration should be tailored for the clinical condition of each individual patient, bearing in mind an insulin-resistance state, especially in hemodialysis patients with hypoxemia. A more complete understanding of what regulates insulin resistance and consequent hyperinsulinemia in endstage renal disease (ESRD) awaits the elucidation of carbohydrate and insulin metabolism.     

Effects of phospholipids on antiganglioside antibody reactivity in GBS

Serum antibody activities to mixtures of a ganglioside and various phospholipids were compared with those to a ganglioside alone in 30 anti-GM1 IgG-positive GBS patients and 30 anti-GQ1b IgG-positive Miller Fisher syndrome (MFS) patients. Anti-GM1-positive sera had higher antibody reactivities against a mixture of GM1 and several phospholipids including PA, PI and PS, than against GM1 alone. In contrast, in case of anti-GQ1b antibody, no phospholipid provided significant enhancement. Sphingomyelin provided decrease of the activity for both anti-GM1 and anti-GQ1b IgG. The effects of phospholipids must be considered to determine the pathogenetic role of antiganglioside antibodies in GBS and MFS.     

Heparan sulfate deficiency in periocular mesenchyme causes microphthalmia and ciliary body dysgenesis

The heparan sulfate (HS) is a component of proteoglycans in the extracellular matrix and on cell surfaces, modulating developmental processes. The aim of this study is to investigate whether the defect of HS in the periocular mesenchyme impairs ocular morphogenesis. First, using Protein 0-Cre transgenic mice, we ablated Ext1, which encodes an indispensable enzyme for HS synthesis, in the developing periocular mesenchyme. The expression of Ext1 messenger RNA (mRNA) and HS were observed by RT-PCR and immunohistochemistry, respectively. The phenotypes in the mutant were evaluated by light microscopy and immunohistochemistry for cellular makers. Second, the distribution of the mutant periocular mesenchymal cells was tracked using a Rosa26 Cre-reporter gene. No mutant embryos (Protein 0-Cre;Ext1^flox/flox) were identified after embryonic day 14.5 (E14.5). RT-PCR showed that an intense band amplified from Ext1 was observed in cDNAs from the control periocular mesenchymal cells at E13.5; however, the band for Ext1 was hardly detectable in cDNA from the mutant embryo, indicating that the mRNA was missing in the mutant periocular mesenchyme at E13.5. The HS expression was disrupted in the periocular mesenchyme of the mutant ocular tissues. The HS deficiency resulted in microphthalmia with reduced axial lengths, lens diameters, and vitreous sizes compared with the littermate eyes. The mutant embryos showed agenesis of the anterior chamber, where cells expressing Cre recombinase were distributed. Moreover, the mutants showed phenotypic alterations in the neural ectoderm including dysgenesis of the presumptive ciliary body and agenesis of the optic nerve head. These findings demonstrate that HS in the periocular mesenchyme plays a critical role in normal ocular morphogenesis, indicating reciprocal interactions between the periocular mesenchyme and the neural ectoderm.     

Administration of alfacalcidol for patients with predialysis chronic kidney disease may reduce cardiovascular disease events

Background

Besides its effect on calcium metabolism, vitamin D may play a part in preventing the onset and progression of cardiovascular disease (CVD) events. Only a few reports on the studies relating to whether vitamin D may reduce CVD events in patients with predialysis chronic kidney disease (CKD) are available, and many ambiguities remain.

Methods

We conducted a retrospective cohort study of 665 patients with predialysis CKD. With log-rank test using the Kaplan–Meyer survival curve, comparison of incidences of CVD events, CVD-related mortality, and all-cause mortality were made between patients in the alfacalcidol treatment group (107 patients) in the predialysis stage to whom alfacalcidol 0.25–0.5 μg/day was orally administered for at least 24 weeks, and patients in the nontreatment group (558 patients) who received no administration of alfacalcidol or other type of activated vitamin D and its analogues. Patients to whom alfacalcidol administration was discontinued within 24 weeks as well as initiation of dialysis of <24 weeks were excluded for this study. Factors relating to CVD events were examined using Cox’s proportional hazards analysis.

Results

The mean follow-up period was 55.1 ± 38.9 months in the alfacalcidol treatment group and 41.9 ± 38.4 months in the nontreatment group. CVD events occurred in 172 patients during the follow-up period, and 74 of those occurred during the predialysis period. In the alfacalcidol treatment group, the incidence of cumulative CVD events was significantly lower. In relation to all-cause deaths and CVD-related deaths, the cumulative mortality rate was significantly lower in the alfacalcidol treatment group during the follow-up period. Throughout the follow-up period, the association between CVD events and alfacalcidol use was detected when adjusted for age, sex, diabetes, hypertension, use of renin–angiotensin system inhibitors, estimated glomerular filtration rate, and albumin and parathyroid hormone.

Conclusion

These data showed that oral administration of alfacalcidol for predialysis CKD patients was associated with reduced risk for CVD.     

Phylogenetic, ontogenetic, and pathological aspects of the urine-concentrating mechanism

The urine-concentrating mechanism is one of the most fundamental functions of avian and mammalian kidneys. This particular function of the kidneys developed as a system to accumulate NaCl in birds and as a system to accumulate NaCl and urea in mammals. Based on phylogenetic evidence, the mammalian urine-concentrating mechanism may have evolved as a modification of the renal medulla's NaCl accumulating system that is observed in birds. This qualitative conversion of the urine-concentrating mechanism in the mammalian inner medulla of the kidneys may occur during the neonatal period. Human kidneys have several suboptimal features caused by the neonatal conversion of the urine-concentrating mechanism. The urine-concentrating mechanism is composed of various functional molecules, including water channels, solute transporters, and vasopressin receptors. Abnormalities in water channels aquaporin (AQP)1 and AQP2, as well as in the vasopressin receptor V2R, are known to cause nephrogenic diabetes insipidus. An analysis of the pathological mechanism involved in nephrogenic diabetes insipidus suggests that molecular chaperones may improve the intracellular trafficking of AQP2 and V2R, and, in the near future, such chaperones may become a new clinical tool for treating nephrogenic diabetes insipidus.     

Neuroradiologic findings in Sotos syndrome

Sotos syndrome is a well-known anomaly syndrome characterized by overgrowth, characteristic facial gestalt, and developmental delay, and haploinsufficiency of the NSD1 gene has been revealed as one of the major genetic causes. However, there have been only a few reports on neuroradiologic findings by computed tomography (CT) or magnetic resonance imaging (MRI), and functional examination of the brain has not been reported. We examined three cases with typical Sotos syndrome, which also were confirmed by genetic analysis with a specific probe for the NSD1 gene. The results of MRI showed the characteristic features that have been reported previously. The findings obtained by using single-photon emission computed tomography and magnetic resonance spectroscopy suggested an association between mental delay and behavioral tendency in Sotos syndrome and immaturity in frontal brain function.     

Evaluation of risk of liver metastasis in colorectal adenocarcinoma based on the combination of risk factors including CD10 expression: multivariate analysis of clinicopathological and immunohistochemical factors

Evaluation of the relationship between clinicopathological and immunohistochemical risk factors for liver metastasis, including CD10 expression, is meaningful in colorectal carcinoma (CRC). The purpose of the present study was to clarify what kind of risk factors are significant and independent factors for the development of liver metastasis in CRC. Sixty cases of advanced CRC with synchronous liver metastasis and sixty cases of advanced CRC without liver metastasis at least 5 years after resection of the primary CRC were randomly selected. We analysed the clinicopathological factors and the expression of four biological factors, CD44, transforming growth factor alpha (TGF-alpha), vascular endothelial growth factor (VEGF) and CD10, by immunohistochemistry. Univariate analysis revealed that the incidence of vascular invasion, the incidence of lymph node metastasis and the expression of CD44, TGF-alpha, VEGF and CD10 were all significantly higher in the cases of CRC with liver metastasis than in cases of non-metastatic CRC. Logistic regression analysis showed that lymph node metastasis, the expression of CD10 and the expression of VEGF were significant factors and independent of the other variables. If all three markers are positive, the probability of liver metastasis becomes 92.7%. In this study, lymph node metastasis, CD10 and VEGF were all found to be significant risk factors for the development of liver metastasis in the cases of CRC. These risk factors according to multivariate analysis are candidate markers for predicting the development of liver metastasis.