Potential of Rice-Flour Jelly Made from High-Amylose Rice as a Dysphagia Diet: Evaluation of Pharyngeal Residue by FEES.

Dysphagia diets are recommended to prevent choking and aspiration in people with dysphagia; however, rice-porridge and mashed rice-porridge, which are used as staple foods for people with dysphagia in Japan, are time-consuming to prepare. The National Agriculture and Food Research Organization has found jelly-like food products made from high-amylose rice-flour (rice-flour jelly) to be easy to prepare with a texture suitable for dysphagia diets. To investigate the potential of rice-flour jelly for the dysphagia diet, we evaluated the amount of pharyngeal residue after swallowing rice-flour jelly using fiberoptic endoscopic evaluation of swallowing and compared it with those of rice-porridge, mashed rice-porridge, and fruit jelly. We enrolled 70 participants (43 males and 27 females, aged 32-96 years, median 74.5 years) and evaluated their pharyngeal residue using the Yale Pharyngeal Residue Severity Rating Scale which includes five levels from I (none) to V (severe). Statistical analysis showed that level I was more common in fruit jelly for vallecula residue and pyriform sinus residue, and level III (mild) was more common in rice-porridge for vallecula residue (p < 0.05). No differences of pharyngeal residue were found in rice-flour jelly or mashed rice-porridge. No significant difference was observed in the number of participants with laryngeal penetration or aspiration. Therefore, rice-flour jelly is a suitable alternative to rice-porridge as a staple food for people with dysphagia in terms of food texture.

Renal infiltration of peripheral T-cell lymphoma, not otherwise specified, mimicking drug-induced acute interstitial nephritis.

Renal invasion of T-cell lymphoma does not usually occur. The renal infiltration of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), is rare. Therefore, the detailed pathology, clinical features, and effective therapy of this type of extranodal disease remain uncovered. Here, we report the rare case of acute kidney injury (AKI) caused by the renal infiltration of PTCL-NOS with no evidence of lymphadenopathy and extranodal lesions, except for the kidney. We mistakenly diagnosed our patient with drug-induced acute interstitial nephritis (AIN) at first, because his clinical features were similar to those of drug-induced AIN; however, we reached the correct diagnosis by detecting atypical T-cells in his urine. After the introduction of cyclophosphamide, doxorubicin, vincristine, and prednisone therapy his general condition improved rapidly. When suspecting drug-induced AIN as the cause of AKI, PTCL-NOS should also be recognized as one of the causes, and urine cytology may be useful to noninvasively distinguish between the two diseases.

Atypical familial Mediterranean fever developed in a long-term hemodialysis patient.

Familial Mediterranean Fever (FMF) is usually an autosomal recessive autoinflammatory disease characterized by recurrent attacks of fever and serositis. FMF develops before the age of 20 years in 90% of patients. It has intervals of 1 week to several years between attacks, which leads to renal dysfunction-amyloidosis. We report a case of atypical FMF that developed in a long-term hemodialysis patient. A 65-year-old Japanese female undergoing hemodialysis for 32 years was referred to our hospital with a fever of unknown origin (FUO) following cervical laminoplasty. The fever occurred as recurrent attacks accompanied by oligoarthralgia of the left hip and knee. We suspected FMF because of recurrent self-limited febrile attacks, although the patient showed atypical clinical features such as late-onset and highly frequent attacks. After receiving treatment, she achieved a complete response to colchicine. Therefore, a diagnosis of FMF was made based on the Tel-Hashomer criteria, which was confirmed by genetic testing. The case suggests that FMF may be of note in long-term hemodialysis patients developing FUO.

Focal segmental glomerulosclerosis; why does it occur segmentally?

Podocyte loss is the fundamental basis of glomerulosclerosis. Focal segmental glomerulosclerosis (FSGS) is a progressive glomerular disease, and its glomerular features are a prototype of podocyte loss-driven glomerulosclerosis. The glomerular pathology of FSGS is characterized by a focal and segmental location of the sclerotic lesions in human FSGS; segmental sclerosis often shows simultaneous intra- and extra-capillary changes, including parietal cell migration, capillary collapse, hyaline deposition, and intra-capillary thrombi and occasional hypercellularity. This suggests that local cellular events, initiated by podocyte loss, are the basis of the segmental lesions in FSGS. Using podocyte-specific injury by toxin administration, a series of recent works has identified the cellular basis of the glomerular response to podocyte loss. This review discusses the molecular pathway of the local response to podocyte loss and its progression to sclerosis. Recent results suggest that segmental sclerosis is a physiological tissue response aimed at halting protein leakage from a disrupted filtration barrier.

Podocyte injury-driven lipid peroxidation accelerates the infiltration of glomerular foam cells in focal segmental glomerulosclerosis.

Intracapillary foam cell infiltration with podocyte alterations is a characteristic pathology of focal segmental glomerulosclerosis (FSGS). We investigated the possible role of podocyte injury in glomerular macrophage and foam cell infiltration in a podocyte-selective injury model (NEP25 mice) and hypercholesterolemic model [low-density lipoprotein receptor deficiency (LDLR(-/-)) mice] with doxorubicin-induced nephropathy. Acute podocyte selective injury alone failed to induce glomerular macrophages in the NEP25 mice. However, in the doxorubicin-treated hypercholesterolemic LDLR(-/-) mice, glomerular macrophages/foam cells significantly increased and were accompanied by lipid deposition and the formation and ingestion of oxidized phospholipids (oxPLs). Glomerular macrophages significantly correlated with the amount of glomerular oxPL. The NEP25/LDLR(-/-) mice exhibited severe hypercholesterolemia, glomerular lipid deposition, and renal dysfunction. Imaging mass spectrometry revealed that a major component of oxidized low-density lipoprotein, lysophosphatidylcholine 16:0 and 18:0, was present only in the glomeruli of NEP25/LDLR(-/-) mice. Lysophosphatidylcholine 16:0 stimulated mesangial cells and macrophages, and lysophosphatidylcholine 18:0 stimulated glomerular endothelial cells to express adhesion molecules and chemokines, promoting macrophage adhesion and migration in vitro. In human FSGS, glomerular macrophage-derived foam cells contained oxPLs accompanied by the expression of chemokines in the tuft. In conclusion, glomerular lipid modification represents a novel pathology by podocyte injury, promoting FSGS. Podocyte injury-driven lysophosphatidylcholine de novo accelerated glomerular macrophage-derived foam cell infiltration via lysophosphatidylcholine-mediated expression of adhesion molecules and chemokines in glomerular resident cells.

Podocyte injury-driven intracapillary plasminogen activator inhibitor type 1 accelerates podocyte loss via uPAR-mediated ß1-integrin endocytosis.

Podocyte-endothelial cell cross-talk is paramount for maintaining the filtration barrier. The present study investigated the endothelial response to podocyte injury and its subsequent role in glomerulosclerosis using the podocyte-specific injury model of NEP25/LMB2 mice. NEP25/LMB2 mice showed proteinuria and local podocyte loss accompanied by thrombotic microangiopathy on day 8. Mice showed an increase of glomerular plasminogen activator inhibitor type 1 (PAI-1) mRNA and aberrant endothelial PAI-1 protein already on day 1, before thrombosis and proteinuria. A PAI-1-specific inhibitor reduced proteinuria and thrombosis and preserved podocyte numbers in NEP25/LMB2 mice by stabilization of ß1-integrin translocation. Heparin loading significantly reduced thrombotic formation, whereas proteinuria and podocyte numbers were unchanged. Immortalized podocytes treated with PAI-1 and the urokinase plasminogen activator (uPA) complex caused significant cell detachment, whereas podocytes treated with PAI-1 or uPA alone or with the PAI-1/uPA complex pretreated with an anti-uPA receptor (uPAR) antibody failed to cause detachment. Confocal microscopy and cell surface biotinylation experiments showed that internalized ß1-integrin was found together with uPAR in endocytotic vesicles. The administration of PAI-1 inhibitor or uPAR-blocking antibody protected cultured podocytes from cell detachment. In conclusion, PAI-1/uPA complex-mediated uPAR-dependent podocyte ß1-integrin endocytosis represents a novel mechanism of glomerular injury leading to progressive podocytopenia. This aberrant cross-talk between podocytes and endothelial cells represents a feedforward injury response driving podocyte loss and progressive glomerulosclerosis.

Induction of labour and intrapartum care in obese women.

The rising incidence of obesity in pregnancy has a significant impact on the provision of health services around the world. Due to the pathophysiological processes associated with the condition, the obese pregnant woman is at increased risks of induction of labour, caesarean section, post-partum haemorrhage, infection, longer hospital stay, macrosomia and higher perinatal morbidity and mortality. Labour is more likely to be prolonged and dysfunctional, leading to the requirements for higher doses of oxytocin and increased risks of operative deliveries and morbidity. A multidisciplinary approach to the planning of antenatal, intrapartum and postnatal care is vital to ensure a safe outcome for the obese pregnant woman and her baby. The need for supervision and attendance by senior obstetric staff is increased, emphasising the need to identify the appropriate place of birth for this high-risk group of women, placing a significant strain on the resources of health-care providers.

The direction and role of phenotypic transition between podocytes and parietal epithelial cells in focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a podocyte disease. Among the various histologies of FSGS, active epithelial changes, hyperplasia, as typically seen in the collapsing variant, indicates disease progression. Using a podocyte-specific injury model of FSGS carrying a genetic podocyte tag combined with double immunostaining by different sets of podocytes and parietal epithelial cell (PEC) markers [nestin/Pax8, Wilms' tumor-1 (WT1)/claudin1, and podocalyxin/Pax2], we investigated the direction of epithelial phenotypic transition and its role in FSGS. FSGS mice showed progressive proteinuria and renal dysfunction often accompanied by epithelial hyperplasia, wherein 5-bromo-4-chloro-3-indoyl ß-d-galactoside (X-gal)-positive podocyte-tagged cells were markedly decreased. The average numbers of double-positive cells in all sets of markers were significantly increased in the FSGS mice compared with the controls. In addition, the average numbers of double-positive cells for X-gal/Pax8, nestin/Pax8 and podocalyxin/Pax2 staining in the FSGS mice were comparable, whereas those of WT1/claudin1 were significantly increased. When we divided glomeruli from FSGS mice into those with FSGS lesions and those without, double-positive cells tended to be more closely associated with glomeruli without FSGS lesions compared with those with FSGS lesions. Moreover, the majority of double-positive cells appeared to be isolated and very rarely associated with FSGS lesions (1/1,997 glomeruli). This study is the first to show the incidence and localization of epithelial cells with phenotypical changes in FSGS using a genetic tag. The results suggest that the major direction of epithelial phenotypic transition in cellular FSGS is from podocytes to PECs and that these cells were less represented in the active lesions of FSGS.

Aberrant Notch1-dependent effects on glomerular parietal epithelial cells promotes collapsing focal segmental glomerulosclerosis with progressive podocyte loss.

Collapsing focal segmental glomerulosclerosis (cFSGS) is a progressive kidney disease characterized by glomerular collapse with epithelial hyperplasia. Here we used a transgenic mouse model of cFSGS with immunotoxin-induced podocyte-specific injury to determine the role for Notch signaling in its pathogenesis. The mice exhibited progressive loss of podocytes and severe proteinuria concomitant with histological features of cFSGS. Hyperplastic epithelium was negative for genetic podocyte tags, but positive for the parietal epithelial cell marker claudin-1, and expressed Notch1, Jagged1, and Hes1 mRNA and protein. Enhanced Notch mRNA expression induced by transforming growth factor-ß1 in cultured parietal epithelial cells was associated with mesenchymal markers (α-smooth muscle actin, vimentin, and Snail1). Notch inhibition in vitro suppressed these phenotypic transcripts and Notch-dependent cell migration. Moreover, Notch inhibition in vivo significantly decreased parietal epithelial cell lesions but worsened proteinuria and histopathology in our cFSGS model. Thus, aberrant Notch1-mediated parietal epithelial cell migration with phenotypic changes appears to underlie the pathogenesis of cFSGS. Parietal epithelial cell hyperplasia may also represent an adaptive response to compensate for a disrupted filtration barrier with progressive podocyte loss.

Assessment and significance of abdominal aortic calcification in chronic kidney disease.

BACKGROUND: Abdominal aortic calcification is a common complication and a predictor of cardiovascular mortality in dialysis patients. However, abdominal aortic calcification in pre-dialysis chronic kidney disease (CKD) is poorly understood. METHODS: A cohort study of 101 adult Japanese patients (mean age 66.6 +/- 11.3 years old) with pre-dialysis CKD (18, 29 and 54 in stages 3, 4 and 5, respectively) was performed. At entry, a non-contrast computed tomography scan was used to determine the abdominal aortic calcification index (ACI). Clinical characteristics and laboratory variables were also assessed. The patients were followed for a mean period of 48 +/- 12 months. RESULTS: Among the subjects, 82% had abdominal aortic calcification (50, 83 and 91% for CKD stages 3, 4 and 5, respectively), and the median ACI was 16.7% (8.5, 20.0 and 21.4%, respectively). Multivariate logistic regression analyses identified older age, presence of diabetes and decreased estimated glomerular filtration rate (e-GFR) as independent predictors of the presence (ACI > 0%) and extent (ACI >or= 20%) of aortic calcification. Multivariate Cox proportional hazards analysis identified ACI >or= 20% and diabetes as independent predictors for de novo cardiovascular events in CKD stages 4 and 5. CONCLUSION: Decreased GFR may be associated with the presence and extent of abdominal aortic calcification, and a high level of calcification may be associated with de novo cardiovascular events in pre-dialysis CKD, suggesting that elucidation of the mechanism through which CKD contributes to vascular calcification may lead to an improved prognosis in patients with pre-dialysis CKD.

[Case of Henoch-Schönlein purpura nephritis successfully treated with tonsillectomy and steroid pulse therapy].

A 30-year-old Japanese man was admitted to our hospital because of fever, sore throat, abdominal pain, purpura skin lesion of the lower legs, and macrohematuria. On admission, his urine was positive (++) for protein; the sediment contained 100 red blood cells per high-power field, and the daily proteinuria level was 1.7 g. Renal biopsy was performed, and we diagnosed Henoch-Schönlein purpura nephritis (HSPN). Six months after the renal biopsy, the patient underwent a tonsillectomy. The pathological diagnosis of the resected tonsils was chronic tonsillitis. After tonsillectomy, the daily proteinuria had decreased to 0.1 g and the sediment contained only 10-19 red blood cells per high-power field. High-dose methylprednisolone therapy (500 mg/day for 3 days for three courses) was started two weeks after the tonsillectomy, followed by oral prednisolone at the initial dose of 30 mg on alternate days. The oral prednisolone was tapered gradually over 1 year. Antiplatelet drug (dipyridamole, 300 mg/day) and angiotensin II receptor antagonist (olmesartan, 10 mg/day) were also administered. This combination therapy resulted in a significant decrease in proteinuria and disappearance of microhematuria. The patient finally achieved clinical remission. Recent reports have shown that in patients with IgA nephropathy, combined tonsillectomy and methylprednisolone pulse therapy have an effect on clinical remission. In addition, it has been suggested that HSPN and IgA nephropathy represent a spectrum of clinical presentations of similar disorders. The result of this case indicated that this combination therapy had a favorable effect on clinical remission in adult patients with HSPN.

Catheter-related bacteremia caused by Agrobacterium radiobacter in a hemodialysis patient.

Agrobacterium radiobacter, a Gram-negative bacillus, is recognized as an emerging opportunistic human pathogen that has a propensity to cause infections in patients with indwelling foreign devices. Here, we describe the first reported case of catheter-related bacteremia caused by A. radiobacter in a hemodialysis patient with a long-term tunneled-cuffed hemodialysis catheter. This case shows that A. radiobacter should be included in the list of pathogens that can cause catheter-related bacteremia in hemodialysis patients.