Fractional excretion of total protein in patients with nephrotic syndrome.

BACKGROUND: The urine protein to creatinine ratio (UPCR) correlates well with the 24-h urine protein test (24-h UPT) and is a reliable indicator of proteinuria. However, in nephrotic syndrome, the correlation between the UPCR and the 24-h UPT tends to decrease. To address this, we introduced the fractional excretion of total protein (FETP), which reflects serum total protein and creatinine levels because severe hypoproteinemia and/or elevated serum creatinine levels tend to occur under these conditions. The 24-h UPT corrected for body surface area (BSA) (24-h UPT/BSA) was used to take body size into consideration. The correlation coefficients for 24-h UPT/BSA and FETP and 24-h UPT/BSA and UPCR were calculated. The statistical significance of the differences between these coefficients was also calculated. METHODS: Thirty-six pediatric patients with nephrotic syndrome were included in this study. The FETP was calculated as total protein clearance/creatinine clearance (%). Correlation coefficients were calculated for 24-h UPT/BSA and FETP and 24-h UPT/BSA and UPCR. The statistical significance of the differences between these coefficients was also calculated. RESULTS: The mean ± standard error of FETP was 0.11% ± 0.013%. The correlation coefficients of FETP and UPCR with 24-h UPT/BSA were 0.91 and 0.81, respectively. The FETP demonstrated a significantly stronger correlation with 24-h UPT/BSA than with UPCR (p = 0.01). CONCLUSIONS: The FETP correlated more strongly with 24-h UPT/BSA than with UPCR in patients with nephrotic syndrome. The FETP is a reliable indicator of proteinuria in nephrotic syndrome, especially in patients with severe hypoproteinemia or elevated serum creatinine levels.

Diversity of cortical bone morphology in anuran amphibians.

The cortical bones of mammals, birds, and reptiles are composed of a complex of woven bone and lamellar bone (fibrolamellar bone) organized into a variety of different patterns; however, it remains unclear whether amphibians possess similar structures. Importantly, to understand the evolutionary process of limb bones in tetrapods, it is necessary to compare the bone structure of amphibians (aquatic to terrestrial) with that of amniotes (mostly terrestrial). Therefore, this study compared the cortical bones in the long bones of several frog species before and after metamorphosis. Using micro-computed tomography (CT), we found that the cortical bones in the fibrolamellar bone of Xenopus tropicalis (Pipoidea superfamily) and Lithobates catesbeianus (Ranoidea superfamily) froglets are dense, whereas those of Ceratophrys cranwelli (Hyloidea superfamily) are porous. To clarify whether these features are common to their superfamily or sister group, four other frog species were examined. Histochemical analyses revealed porous cortical bones in C. ornata and Lepidobatrachus laevis (belonging to the same family, Ceratophryidae, as C. cranwelli). However, the cortical bones of Dryophytes japonicus (Hylidae, a sister group of Ceratophryidae in the Hyloidea superfamily), Microhyla okinavensis (Microhylidae, independent of the Hyloidea superfamily), and Pleurodeles waltl, a newt as an outgroup of anurans, are dense with no observed cavities. Our findings demonstrate that at least three members of the Ceratophryidae family have porous cortical bones similar to those of reptiles, birds, and mammals, suggesting that the process of fibrolamellar bone formation arose evolutionarily in amphibians and is conserved in the common ancestor of amniotes.

The impact of uncertainty in society on the use of traditional, complementary and alternative medicine: a comparative study on visits to alternative/traditional/folk health care practitioners.

BACKGROUND: While traditional, complementary and alternative medicine (TCAM) is gaining increased interest worldwide, the structural factors associated with the usage of TCAM at the social level have not been sufficiently explored. We aim to understand the social structure of uncertainty in society that affects the TCAM usage for men and women. METHODS: We studied 32 countries using data from the International Social Survey Programme and the World Bank. In this study, we defined TCAM usage as visits to an alternative/traditional/folk health care practitioner during the past 12 months. We performed a correlation analysis and used a generalized linear model . RESULTS: The prevalence of TCAM usage in terms of visits to practitioners was 26.1% globally, while usage varied across the 32 countries. Generalized linear models showed that unemployment rate was associated with the prevalence of TCAM usage in terms of visits to practitioners. CONCLUSIONS: At the social-structural level TCAM usage involving visits to practitioners was related to job insecurity. Job insecurity led to a decrease in TCAM usage regarding visits to practitioners. These findings suggest that it is necessary to consider the social-structural factors of uncertainty in society when designing health policies related to TCAM.

[A Resected Case with Early Gastric Cancer That Was Overdiagnosed as Scirrhous Gastric Cancer].

We experienced a case of early gastric cancer. A 69-year-old woman with a thick gastric wall, thickened folds, and undifferentiated cancer cells in biopsy was diagnosed with scirrhous gastric cancer. The patient underwent total gastrectomy for scirrhous gastric cancer and was found to have only an early gastric cancer lesion located on the upper gastric wall. The thick wall diagnosed before surgery was diagnosed as angiodysplasia occupying the submucosal layer.

Application of Muse Cell Therapy for Kidney Diseases.

The kidney plays an essential role in the maintenance of homeostasis in healthy individuals, e.g., by regulating the amount of water and concentration of electrolyte in the body. Owing to the structural complexity, renal dysfunction is caused by a myriad of diseases and conditions, and in severe cases, it progresses to end-stage renal disease in which patients require renal replacement therapy, i.e., maintenance dialysis or kidney transplantation. The currently available therapeutic modalities, with the exception of renal transplantation, cannot recover severely deteriorated renal function. Thus, regenerative medicine holds considerable promise as a potential means for developing next-generation renal therapeutics. Mesenchymal stem cell (MSC) transplantation has been investigated in acute kidney injury and chronic kidney disease models, and clinical studies have already been started for some kinds of kidney diseases. However, most of these studies concluded that the main underlying mechanism of therapeutic effect of MSC transplantation was paracrine. Recently, we reported that Muse cell therapy in a murine model of chronic kidney disease resulted in differentiation of intravenously injected Muse cells into glomerular cells after preferential homing to damaged glomerulus and improvement in renal function. The result suggested the potentiality of Muse cell therapy for glomerular regeneration. Muse cells are a promising cell source for regenerative therapy for kidney diseases.

Preoperative sonographic evaluation of the defect size and the diaphragm rim in congenital diaphragmatic hernia - preliminary experience.

BACKGROUND: Sonographic assessment before congenital diaphragmatic hernia repair has rarely been studied. OBJECTIVE: To evaluate the accuracy of preoperative ultrasound in measuring the defect size and in anticipating the presence of a rim and thereby to determine ultrasound's usefulness in informing the surgical approach for definitive repair of congenital diaphragmatic hernia. MATERIALS AND METHODS: We performed a retrospective review of the medical records of seven children with left congenital diaphragmatic hernia who had undergone ultrasound and definitive repair between 2014 and 2017 at our institution. RESULTS: The estimated defect size by ultrasound to the actual defect size measured intraoperatively for each case were as follows: 23 × 25 mm to 20 × 26 mm (case 1); 23 × 30 mm to 20 × 30 mm (case 2); 43 × 25 mm to 30 × 30 mm (case 3); 21 × 23 mm to 20 × 25 mm (case 4); 19 × 24 mm to 10 × 30 mm (case 5); 32 × 33 mm to 30 × 50 mm (case 6); and almost total absence to 40 × 50 mm (case 7). Presence or absence of each part of the diaphragm rim evaluated by ultrasound was almost identical with the actual intraoperative findings. According to the ultrasound findings, we performed a successful thoracoscopic repair in cases 1-5 with relatively small defects and presence of all parts of the rim or absence of only posterolateral rim. CONCLUSION: There was good concordance between ultrasound findings and operative findings regarding the size of the defect and presence or absence of the diaphragm rim.

Beneficial Effects of Systemically Administered Human Muse Cells in Adriamycin Nephropathy.

Multilineage-differentiating stress-enduring (Muse) cells are nontumorigenic endogenous pluripotent-like stem cells that can be collected from various organs. Intravenously administered Muse cells have been shown to spontaneously migrate to damaged tissue and replenish lost cells, but the effect in FSGS is unknown. We systemically administered human bone marrow-derived Muse cells without concurrent administration of immunosuppressants to severe combined immune-deficient (SCID) and BALB/c mouse models with adriamycin-induced FSGS (FSGS-SCID and FSGS-BALB/c, respectively). In FSGS-SCID mice, human Muse cells preferentially integrated into the damaged glomeruli and spontaneously differentiated into cells expressing markers of podocytes (podocin; 31%), mesangial cells (megsin; 13%), and endothelial cells (CD31; 41%) without fusing to the host cells; attenuated glomerular sclerosis and interstitial fibrosis; and induced the recovery of creatinine clearance at 7 weeks. Human Muse cells induced similar effects in FSGS-BALB/c mice at 5 weeks, despite xenotransplant without concurrent immunosuppressant administration, and led to improvement in urine protein, creatinine clearance, and plasma creatinine levels more impressive than that in the FSGS-SCID mice at 5 weeks. However, functional recovery in FSGS-BALB/c mice was impaired at 7 weeks due to immunorejection, suggesting the importance of Muse cell survival as glomerular cells in the FSGS kidney for tissue repair and functional recovery. In conclusion, Muse cells are unique reparative stem cells that preferentially home to damaged glomeruli and spontaneously differentiate into glomerular cells after systemic administration. Introduction of genes to induce differentiation is not required before Muse cell administration; thus, Muse cells may be a feasible therapeutic strategy in FSGS.

Prediction of Poor Prognosis After Severe Head Injury in Children Using Logistic Regression.

OBJECTIVES: Head trauma is one of the main causes of death in childhood and often leaves severe disability with serious neurological damage. Appropriate treatment must be provided immediately to improve outcomes. This study was performed to identify factors associated with a poor prognosis at an early stage of severe head injury in children. METHODS: The subjects were registered in the Japan Neurotrauma Data Bank. They were 119 children (mean age, 8 years; male, 67.2%) with severe head injury registered during a period of 4 years (from July 1, 2004 to June 30, 2006 and from July 1, 2009 to June 30, 2011). Univariate and multivariate analyses were performed to examine relationships among factors and outcome 6 months after discharge. Logistic regression analysis was performed to develop models for poor prognosis and death. RESULTS: Outcome was evaluated based on the Glasgow Outcome Scale: 73 children (61.3%) had good recovery, 11 (9.2%) had moderate disability, 8 (6.7%) had severe disability, 4 (3.3%) were in a vegetative state, and 23 (19.3%) had died. Four factors were identified as predictors of a poor prognosis: serum glucose level greater than or equal to 200 mg/dL, Glasgow Coma Scale score on admission less than or equal to 5, presence of mydriasis, and presence of traumatic subarachnoid hemorrhage. Three factors were identified as predictors of death: serum glucose level greater than or equal to 200 mg/dL, Glasgow Coma Scale score on admission less than or equal to 5, and presence of mydriasis. CONCLUSIONS: Using these predictors, subsequent exacerbation may be predicted just after arrival at the hospital and appropriate treatment can be provided immediately.

Transfusion-associated hypoxemia in pediatric patients with solid tumors after autologous peripheral blood stem cell transplantation.

BACKGROUND: Although several types of transfusion-related adverse reactions (TRARs) have been reported, one of the most important involves respiratory features during and after blood transfusion. Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are the most severe adverse events following blood transfusion, whereas transfusion-associated dyspnea　(TAD) is a less severe respiratory distress. However, there exists little evidence of these factors in pediatric populations. CASE REPORT: Here, two cases of atypical TRARs with respiratory features, in pediatric patients with solid tumors, appearing after transfusion of platelet concentrate following autologous peripheral blood stem cell transplantation are reported. Both patients developed mild hypoxemia during PC transfusion, which continued for approximately 2 weeks. Chest radiography in either patient did not reveal any abnormalities that are included in the criteria of either TRALI or TACO. Both patients recovered following oxygen administration. CONCLUSION: This complication of TRARs with respiratory features may occur more frequently in pediatric populations than realized because it may be under-recognized or under-reported. Accumulation of additional cases, including non-typical cases, is necessary to fully understand the pathology of TRARs, correctly classify these reactions, and improve care of patients receiving blood transfusions.

[A Case of Gastric Remnant Cancer after Proximal Gastrectomy with Jejunum Pouch Interposing Reconstruction].

A 83-year-old man was diagnosed an earlygastric remnant cancer on the site of jejuno-gastrostomyafter proximal gastrectomywith jejunum interposing reconstruction 23 years ago. A total gastrectomywas performed due to the difficultyof endoscopic submucosal resection. The surgical operation took 200 minutes and the blood loss was 180 mL. Histologically, tumor size was 28×22mm invading to submucosal layer with a lymph node metastasis. To reduce the risk of surgical operation for gastric remnant cancer of aged patients, a simple reconstruction method is important for proximal gastrectomy, like a esophagogastrostomyplacing a gastric tube in the mediastinum.

[A Patient with Scirrhous Gastric Cancer Diagnosed and Resected Subsequently by Laparotomy Examination Due to Difficulty to Take Cancer Specimen by Endoscopic Biopsy].

Some of scirrhous gastric cancer are difficult to diagnose on the surface view or to take correct biopsy specimen.A 85-yearold man with dysphagia was diagnosed scirrhous gastric cancer endoscopically, but could not be taken a biopsy specimen showing cancer.We informed cases of scirrhous gastric cancer difficult to take correct biopsy specimen and recommended surgical operation to take correct specimen and to start a treatment.Patient underwent total gastrectomy after cancer diagnosis( P0CY0cT4aN0).He can eat more food and survive longer than 1 year without any chemotherapies.Scirrhous gastric cancer needs early diagnosis and treatment to improve patient prognosis.

Preoperative Treatment With Pazopanib in a Case of Chemotherapy-Resistant Infantile Fibrosarcoma.

Clinical and radiological diagnosis of infantile fibrosarcoma (IFS) is challenging because of its similarity to vascular origin tumors. Treatment involves complete resection. Although chemotherapy may allow more conservative resection, treatment guidelines are not strictly defined. One IFS patient with an unresectable tumor had disease progression during chemotherapy. A primary tumor sample showed high VEGFR-1/2/3 and PDGFR-α/ß expression. After pazopanib therapy, most tumor showed necrosis within 29 days and could be removed completely, with no relapse in 8 months post-resection. When IFS features hypervascularity, VEGFR and PDGFR expression may be high, thus allowing consideration of VEGFR inhibitors such as pazopanib.

Early RAAS Blockade Exerts Renoprotective Effects in Autosomal Recessive Alport Syndrome.

Alport syndrome is a progressive renal disease caused by mutations in COL4A3, COL4A4, and COL4A5 genes that encode collagen type IV alpha 3, alpha 4, and alpha 5 chains, respectively. Because of abnormal collagen chain, glomerular basement membrane becomes fragile and most of the patients progress to end-stage renal disease in early adulthood. COL4A5 mutation causes X-linked form of Alport syndrome, and two mutations in either COL4A3 or COL4A4 causes an autosomal recessive Alport syndrome. Recently, renin-angiotensin-aldosterone system (RAAS) blockade has been shown to attenuate effectively disease progression in Alport syndrome. Here we present three Japanese siblings and their father all diagnosed with autosomal recessive Alport syndrome and with different clinical courses, suggesting the importance of the early initiation of RAAS blockade. The father was diagnosed with Alport syndrome. His consanguineous parents and his wife were healthy. All three siblings showed hematuria since infancy. Genetic analysis revealed that they shared the same gene mutations in COL4A3 in a compound heterozygous state: c.2330G>A (p.Gly777Ala) from the mother and c.4354A>T (p.Ser1452Cys) from the father. Although RAAS blockade was initiated for the older sister and brother when their renal function was already impaired, it did not attenuate disease progression. In the youngest brother, RAAS blockade was initiated during normal renal function stage. After the initiation, his renal function has been normal with the very mild proteinuria to date at the age of 17 years. We propose that in Alport syndrome, RAAS blockade should be initiated earlier than renal function is impaired.

[Successful Multidisciplinary Treatment of Metastatic Ovarian Cancer after Perforative Peritonitis of the Rectum Due to Disseminated Ovarian Cancer].

A72 -year-old woman who complained of abdominal pain and distention visited the emergency clinic of our hospital in April 2014. Computed tomography(CT)showed an omental mass and a pelvic mass with massive ascites. The fluid was removed by abdominal aspiration, and the patient showed perforative peritonitis next day. An emergency operation was performed. The surgical operation showed that the rectum was perforated due to stenosis covered by the ovarian cancer metastases. Aleft colectomy combined with a transverse colostomy was performed. After 4 weeks of rest, 6 courses of tri- weekly TC chemotherapy were administered, and the CA125 level decreased from 140 U/mL to 11.8 U/mL. She underwent a complete cytoreductive surgery in February 2015. She was histologically diagnosed with Grade 2b serous adenocarcinoma. After these 2 surgical operations, she underwent a splenectomy to remove a single metastasis in February 2016 and consecutive chemotherapy. For ovarian cancer, if dissemination occurs, rectal perforation can be a treatment target with a gastrointestinal surgeon's help.

An approach to medical knowledge sharing in a hospital information system using MCLink.

Clinicians often need access to electronic information resources that answer questions that occur in daily clinical practice. This information generally comes from publicly available resources. However, clinicians also need knowledge on institution-specific information (e.g., institution-specific guidelines, choice of drug, choice of laboratory test, information on adverse events, and advice from professional colleagues). This information needs to be available in real time. This study characterizes these needs in order to build a prototype hospital information system (HIS) that can help clinicians get timely answers to questions. We previously designed medical knowledge units called Medical Cells (MCs). We developed a portal server of MCs that can create and store medical information such as institution-specific information. We then developed a prototype HIS that embeds MCs as links (MCLink); these links are based on specific terms (e.g., drug, laboratory test, and disease). This prototype HIS presents clinicians with institution-specific information. The HIS clients (e.g., clinicians, nurses, pharmacists, and laboratory technicians) can also create an MCLink in the HIS using the portal server in the hospital. The prototype HIS allowed efficient sharing and use of institution-specific information to clinicians at the point of care. This study included institution-specific information resources and advice from professional colleagues, both of which might have an important role in supporting good clinical decision making.

Molecular pathogenesis of pseudohypoaldosteronism type II: generation and analysis of a Wnk4(D561A/+) knockin mouse model.

WNK1 and WNK4 mutations have been reported to cause pseudohypoaldosteronism type II (PHAII), an autosomal-dominant disorder characterized by hyperkalemia and hypertension. To elucidate the molecular pathophysiology of PHAII, we generated Wnk4(D561A/+) knockin mice presenting the phenotypes of PHAII. The knockin mice showed increased apical expression of phosphorylated Na-Cl cotransporter (NCC) in the distal convoluted tubules. Increased phosphorylation of the kinases OSR1 and SPAK was also observed in the knockin mice. Apical localization of the ROMK potassium channel and transepithelial Cl(-) permeability in the cortical collecting ducts were not affected in the knockin mice, whereas activity of epithelial Na(+) channels (ENaC) was increased. This increase, however, was not evident after hydrochlorothiazide treatment, suggesting that the regulation of ENaC was not a genetic but a secondary effect. Thus, the pathogenesis of PHAII caused by a missense mutation of WNK4 was identified to be increased function of NCC through activation of the OSR1/SPAK-NCC phosphorylation cascade.

Absence of ferroelectric critical size in ultrathin PbTiO3 nanotubes: a density-functional theory study.

We simulate from first principles the energetic, structural, and electronic properties of ferroelectric (FE) ultrathin PbTiO3 nanotubes. The nanotube possesses spontaneous polarization despite their sidewalls being thinner than the critical thickness at which the thin films lose ferroelectricity; this indicates the absence of an intrinsic critical size for ferroelectricity. The ground state of the nanotube is not purely FE since it primarily involves antiferrodistortive (AFD) rotations of oxygen atoms due to compression in the inner tube wall. The emergence of the AFD displacement plays a central role in stabilizing both the nanotubular structure and FE distortions due to direct AFD-FE coupling. Moreover, we predict intriguing rich phase transitions due to axial strains including polarization vortices as an important class of nanoscale FE ordering.

Generation and analyses of R8L barttin knockin mouse.

Barttin, a gene product of BSND, is one of four genes responsible for Bartter syndrome. Coexpression of barttin with ClC-K chloride channels dramatically induces the expression of ClC-K current via insertion of ClC-K-barttin complexes into plasma membranes. We previously showed that stably expressed R8L barttin, a disease-causing missense mutant, is retained in the endoplasmic reticulum (ER) of Madin-Darby canine kidney (MDCK) cells, with the barttin ß-subunit remaining bound to ClC-K α-subunits (Hayama A, Rai T, Sasaki S, Uchida S. Histochem Cell Biol 119: 485-493, 2003). However, transient expression of R8L barttin in MDCK cells was reported to impair ClC-K channel function without affecting its subcellular localization. To investigate the pathogenesis in vivo, we generated a knockin mouse model of Bartter syndrome that carries the R8L mutation. These mice display disease-like phenotypes (hypokalemia, metabolic alkalosis, and decreased NaCl reabsorption in distal tubules) under a low-salt diet. Immunofluorescence and immunoelectron microscopy revealed that the plasma membrane localization of both R8L barttin and the ClC-K channel was impaired in these mice, and transepithelial chloride transport in the thin ascending limb of Henle's loop (tAL) as well as thiazide-sensitive chloride clearance were significantly reduced. This reduction in transepithelial chloride transport in tAL, which is totally dependent on ClC-K1/barttin, correlated well with the reduction in the amount of R8L barttin localized to plasma membranes. These results suggest that the major cause of Bartter syndrome type IV caused by R8L barttin mutation is its aberrant intracellular localization.

Calcium and calcimimetics regulate paracellular Na+ transport in the thin ascending limb of Henle's loop in mouse kidney.

The effect of Ca(2+) and calcimimetics on NaCl transport was investigated in the in vitro isolated microperfused mouse thin ascending limb of Henle's loop. In the presence of a transmural NaCl gradient, the transepithelial diffusional potential was 13.7 +/- 0.4 mV (n = 17). When the Ca(2+) in the bath was increased from 1.5 to 4.5 mM at 37 degrees C, the relative permeability of Na(+) to Cl(-) (P (Na) /P (Cl)) estimated from the diffusional voltage deflection due to the transepithelial NaCl gradient (V (d)) changed from 0.371 +/- 0.017 to 0.341 +/- 0.015 (n = 10, P < 0.0001). When the Ca(2+) in the lumen was increased from 1.5 to 4.5 mM, the P (Na) /P (Cl) decreased from 0.349 +/- 0.013 to 0.330 +/- 0.013 (n = 5, P < 0.002). The addition of 0.1 mM neomycin and 0.2 mM gentamicin to the bath or lumen also decreased the P (Na) /P (Cl). The same effect on P (Na) /P (Cl) of Ca(2+) and calcimimetics occurred in ClC-K1 (kidney-specific chloride channel) knockout mice. The addition of 300 mug/ml protamine to the bath strongly inhibited changes to P (Na) /P (Cl) induced by basolateral Ca(2+). These data indicate that ambient Ca(2+) and calcimimetics inhibit Na(+) transport in the thin ascending limb, which is known to occur via the paracellular shunt pathway. Our observations strongly suggest that Ca(2+) is involved in the regulation of paracellular Na(+) permeability in the thin ascending limbs.

A Japanese nationwide survey for evaluation of the comprehensibility of alternative audiometry display formats: Insight into otolaryngologists' cognitive processes.

OBJECTIVE: The present study aimed to elucidate opinions regarding comprehensibility of audiometry display formats among otolaryngologists in Japan, and to identify the characteristics of otolaryngologists' cognitive processes for audiometry. METHODS: We conducted a cross-sectional nationwide questionnaire-based mail survey regarding the comprehensibility of audiometry display formats among 543 Japanese otolaryngologists. Of 543 otolaryngologists to whom the questionnaires were mailed, 137 replied to the questions. For the analysis, the sample size used was 112 participants. The questionnaire contained questions regarding the otolaryngologists' occupational characteristics, and assessed their opinions of four comprehensibility aspects of five display formats. RESULTS: Otolaryngologists in clinics indicated that the passage of time and changes in thresholds of each frequency in numeric tables were ordinary or incomprehensible. More than 60% of otolaryngologists with extensive experience in using electronic medical records indicated that both, the passage of time and change in the thresholds in overlaid thresholds on a chart were comprehensible. CONCLUSIONS: Display formats in audiometry influenced the comprehension of pure tone audiometry data. Our results suggest that overlaid thresholds on a chart rather than numeric table or multi-dimensional charts are the primary choice for computerized audiometry display formats in most aspects of audiometry.