Chitin powder enhances growth factor production and therapeutic effects of mesenchymal stem cells in a chronic kidney disease rat model.

Previously, we fabricated a device with polylactic acid nonwoven filters and mesenchymal stem cells (MSCs), which effectively reduced urinary protein levels in a rat model of chronic kidney disease (CKD) but could not suppress CKD progression. Therefore, to improve the therapeutic effects of MSCs, in this study, we analyzed the ability of rat adipose tissue-derived MSCs (ADSCs) in contact with chitin nonwoven filters or chitin powder to produce growth factors and examined their therapeutic effect in an adriamycin (ADR)-induced CKD rat model. Hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) production was significantly enhanced by ADSCs cultured in a medium containing chitin powder (C-ADSCs) compared with that by ADSCs cultured in a standard medium without chitin (N-ADSCs). However, the production of HGF and VEGF by ADSCs on chitin nonwoven filters was not significantly enhanced compared with that by the control. Intravenous C-ADSC injection significantly increased podocin expression and improved proteinuria compared with those in saline-treated CKD rats; however, no such improvements were observed in the N-ADSC-treated group. These results showed that ADSCs cultured in a medium supplemented with chitin powder suppressed proteinuria via enhanced HGF and VEGF production in ADR-induced CKD rats to mitigate podocyte damage, offering a new strategy to reduce the dose of MSC therapy for safe and effective treatment of kidney disease.

Accuracy of diagnosing acute kidney injury by assessing urine output within the first week of life in extremely preterm infants.

BACKGROUND: Neonatal acute kidney injury (AKI) is associated with increased mortality and is often assessed with the neonatal modified Kidney Disease: improving Global Outcomes (KDIGO) classification, which uses changes in serum creatinine levels. However, because this classification has many drawbacks, a novel method, the neonatal Risk, Injury, Failure, Loss, and End-Stage Kidney Disease (nRIFLE) classification for diagnosing neonatal AKI according to urine output (UO), was recently proposed. To date, no data on the incidence of AKI according to nRIFLE are available for extremely preterm infants (born at gestational age less than 28 weeks). This study was conducted to clarify the association between incidence of AKI and in-hospital mortality in extremely preterm infants. METHODS: Of 171 extremely preterm infants hospitalized from 2006 to 2020, 84 in whom indwelling bladder catheters were placed for UO measurements within 24 h of life were included. The incidence of AKI was assessed using the nRIFLE classification. In-hospital mortality was compared between patients with AKI and those without it. RESULTS: The incidence of AKI during the first week of life was 56% and that of in-hospital mortality was significantly higher in patients with AKI (25.5%) than in those without it (2.8%). The odds ratio was 12.3 with 95% confidence interval ranging from 1.5 to 100.0. CONCLUSION: The incidence of AKI according to nRIFLE was higher than reported in most previous studies using the neonatal modified KDIGO classification, suggesting that assessment by nRIFLE criteria using UO may improve diagnostic accuracy of AKI in extremely preterm infants.

Effect of Delivery Mode and Nutrition on Gut Microbiota in Neonates.

BACKGROUND/AIMS: The mode of delivery (vaginal or cesarean section) and feeding type (breastfeeding or formula feeding) of neonates are considered the most influential factors in the development of gut microbiota. OBJECTIVES: This study investigated the effect of prebiotic-rich breast milk on overcoming gut microbiota dysbiosis. METHOD: Stool samples from 36 healthy Japanese neonates were obtained at 4 days and 1 month of age, and divided into 4 groups based on mode of delivery and feeding type. The gut microbiota composition and bacterial diversity were assessed using 16S rRNA sequencing. RESULTS: At 4 days old, vaginally delivered neonates had a significantly higher diversity of bacteria than those born by cesarean section. Bacteroidales and Enterobacteriales were overrepresented in vaginally delivered neonates (p = 0.0031 and p = 0.011), while Bacillales and Lactobacillales were overrepresented in caesarean section delivered neonates (p = 0.012 and p = 0.0016). However, there was little difference in bacterial diversity and bacterial relative abundance at 1 month of age between groups. CONCLUSIONS: Cesarean section delivery appeared to reduce the diversity of neonate gut microbiota, resulting in dysbiosis, but this improved to the equivalent level seen in vaginally delivered infants by 1 month of age. Breastfeeding, even for short periods, may therefore improve neonate gut dysbiosis.

Natural course of isolated mild congenital hydronephrosis: A 2-year prospective study at a single center in Japan.

OBJECTIVES: To determine a follow-up plan for mild congenital hydronephrosis in Japanese individuals. METHODS: Neonates at Kansai Medical University Hospital (Hirakata, Osaka, Japan) who were diagnosed with mild congenital hydronephrosis - defined as a Society for Fetal Urology grade 1 or 2 - at 1-month old by abdominal ultrasonography between 2014 and 2016 were enrolled. These patients were encouraged to undergo repeated abdominal ultrasonography for 2 years every 3 months to investigate the course of congenital hydronephrosis. RESULTS: Among 1009 neonates, congenital hydronephrosis was detected in 118 affected renal units of 100 (9.9%) patients. According to the definition of the Society for Fetal Urology, 118 affected renal units were graded as grade 1 in 87 (74%), grade 2 in 30 (25%), grade 3 in one (1%) and grade 4 in 0 units. Among them, 117 affected renal units of mild congenital hydronephrosis comprising grades 1 and 2 were subjected to ultrasonographic evaluation to monitor the natural course. The rates of resolution at 7, 10, 13, 16, 19, 22 and 25 months after birth in Society for Fetal Urology grades 1 and 2 cases were 60% and 8%, 77% and 19%, 90% and 32%, 92% and 40%, 95% and 52%, 96% and 56%, and 99% and 60%, respectively. CONCLUSIONS: Grade 1 congenital hydronephrosis does not need to be followed up, because it mostly shows spontaneous resolution by 2 years of follow up without any complications. However, ultrasonographic examinations at 1-year intervals for grade 2 congenital hydronephrosis are recommended to determine the subsequent follow-up plan of patients.

Prediction of urine volume soon after birth using serum cystatin C.

BACKGROUND: Urine volume is an important clinical finding particularly during the early neonatal period. Oliguria is not a sign of impaired renal function but also a predictive factor for various complications and prognoses. It has been postulated that serum cystatin C (S-CysC) is a more sensitive biomarker for renal function than serum creatinine (S-Cr) in both adults and children. The objective of the current study was to investigate whether urine volume during 24 h after birth can be predicted using S-CysC. METHODS: The subjects were 87 infants. The average gestational age was 34.7 ± 2.9 weeks and the average birth weight was 2135 ± 614 g. Blood samples were obtained from either the umbilical cord or the peripheral veins or artery of the newborn at birth. Data regarding the amount of urine volume and fluid intake during the first 24 h of life, maternal S-Cr and S-CysC levels within 48 h before delivery, and neonatal S-Cr and S-CysC levels at birth were collected from the medical records. RESULTS: A significantly positive correlation was observed between maternal and neonatal S-Cr levels (r = 0.84, p < 0.0001) but not between maternal S-Cr levels and neonatal S-CysC levels (r = -0.069, p = 0.52). A significant negative correlation was seen between neonatal S-CysC levels and urine volume (r = -0.47, p < 0.0001). CONCLUSION: The present study findings indicate that it may be possible to use S-CysC levels at birth to predict urine volume during the first 24 h of life.

Appropriate nonwoven filters effectively capture human peripheral blood cells and mesenchymal stem cells, which show enhanced production of growth factors.

Scaffolds, growth factors, and cells are three essential components in regenerative medicine. Nonwoven filters, which capture cells, provide a scaffold that localizes and concentrates cells near injured tissues. Further, the cells captured on the filters are expected to serve as a local supply of growth factors. In this study, we investigated the growth factors produced by cells captured on nonwoven filters. Nonwoven filters made of polyethylene terephthalate (PET), biodegradable polylactic acid (PLA), or chitin (1.2-22 µm fiber diameter) were cut out as 13 mm disks and placed into cell-capturing devices. Human mesenchymal stem cells derived from adipose tissues (h-ASCs) and peripheral blood cells (h-PBCs) were captured on the filter and cultured to evaluate growth factor production. The cell-capture rates strongly depended on the fiber diameter and the number of filter disks. Nonwoven filter disks were composed of PET or PLA fibers with fiber diameters of 1.2-1.8 µm captured over 70% of leukocytes or 90% of h-ASCs added. The production of vascular endothelial growth factor (VEGF), transforming growth factor ß1, and platelet-derived growth factor AB were significantly enhanced by the h-PBCs captured on PET or PLA filters. h-ASCs on PLA filters showed significantly enhanced production of VEGF. These enhancements varied with the combination of the nonwoven filter and cells. Because of the enhanced growth factor production, the proliferation of human fibroblasts increased in conditioned medium from h-PBCs on PET filters. This device consisting of nonwoven filters and cells should be investigated further for possible use in the regeneration of impaired tissues.

Elective Cesarean section at 37 weeks is associated with the higher risk of neonatal complications.

Elective Cesarean section performed before 39 weeks of gestation may be associated with increased risk of neonatal complications. We retrospectively investigated differences in the neonatal complication rate between 684 newborns delivered by elective Cesarean section at 37 weeks of gestation (n = 390) and those delivered by the same procedure at 38 weeks (n = 294) between 2006 and 2012 at our hospital in order to ascertain whether adverse outcomes differ between the groups. Newborns delivered at 37 weeks had a significantly higher incidence of neonatal intensive care unit admission (p = 0.03), adverse respiratory complications (p < 0.01), low birth weight (p < 0.001), and hypoglycemia (p < 0.005) than those delivered at 38 weeks. Compared with normal weight neonates, low birth weight neonates were more likely to have hypoglycemia (p < 0.001). Multivariate logistic regression analysis revealed that an adverse respiratory outcome was independently associated with gestational age (p < 0.01; odds ratio [OR], 3.26; 95% confidence interval [CI], 1.36-7.81), while hypoglycemia was independently associated with birth weight (p < 0.01; OR, 16.34; 95% CI, 7.72-34.56). Respiratory disorders were significantly associated with gestational age even in normal birth weight newborns without any other complications such as hyperbirilubinemia, hypoglycemia or bacterial infections. In conclusion, the incidence of neonatal complications was higher in newborns delivered at 37 weeks of gestation than in those delivered at 38 weeks via elective Cesarean section. Thus, the procedure should be scheduled at 38 weeks to improve neonatal outcomes.

Assessing protein and albumin recovery rates in different ascites filtration membrane washing methods for cell-free and concentrated ascites reinfusion therapy.

Objectives: In cell-free and concentrated ascites reinfusion therapy (CART), the protein recovery rate decreases when the filtration membrane gets clogged. Employing a device with a filtration membrane washing feature prevents clogging, but it leads to the loss of ascites within the filter, resulting in reduced protein recovery. This study employed a device with a membrane washing function to investigate the relationship between protein recovery rate and the quantity of washing solution used, depending on the selected washing method. Methods: We analyzed cases of CART conducted at Fujita Health University Hospital between May 2021 and November 2022. The cases were divided and compared between two groups: one using flush and rinse as the washing method (flush+rinse group) and another using only flushing (flush group). Results: We identified nine cases and 16 sessions. In the flush+rinse group, the median amount of washing solution used per membrane washing was 259 mL per cycle, whereas it was 54 mL per cycle in the flush group. This difference was statistically significant (p<0.0001). The median total protein recovery rate was 53.8% for the flush+rinse group and 78.8% for the flush group, with the latter showing a significantly higher value (p=0.0199). Conclusions: In CART using a membrane washing function, adopting a washing method that reduces the amount of washing solution leads to an increase in the total protein recovery rate.

B-type natriuretic peptide for assessment of haemodynamically significant patent ductus arteriosus in premature infants.

AIM: Haemodynamically significant patent ductus arteriosus (hsPDA) is frequently observed in premature infants. This study was conducted to explore whether the blood BNP can be a valuable biomarker to assess the necessity of treatment for hsPDA in premature infants. METHODS: Serial measurements of the blood BNP were performed during the first 5 days of life in premature infants with hsPDA (Group I) and those without hsPDA (Group N). The definition of the hsPDA was the PDA requiring treatment, such as indomethacin administration and/or surgical ligation. RESULTS: Forty-six subjects were enrolled. Compared with Group N, Group I showed significantly higher level of blood BNP at postnatal 24-96 h and demonstrated the peak value at postnatal 24-48 h. With the ROC curve using the data at postnatal 24-48 h in Group I, we deduced the predictive value of 250 pg/mL of blood BNP for indomethacin treatment. Similarly, with the ROC curve using the maximal value of blood BNP within the first 5 days of life, the predictive value of 2000 pg/mL for surgical ligation was deduced. CONCLUSIONS: Blood BNP during early postnatal period can be a useful biomarker to assess the necessity of treatment for hsPDA in premature infants.

A potential therapeutic system for Alzheimer's disease using adsorbents with alkyl ligands for removal of blood amyloid ß.

Amyloid beta proteins (Aß) in the brain are the main cause of Alzheimer's disease. Peripheral administration of Aß-binding substances, which may act as a sink for Aß from the brain, has been reported to reduce brain Aß. We previously found C16-cellulose beads had high Aß-removal activity in vitro. In this study, we investigated the optimum surface properties of adsorbents for removal of Aß in vitro and in humans. Batch analysis was performed with porous cellulose beads or silica beads with or without 2-22 methylene groups. Aß-removal activity of C16-cellulose beads increased with increasing alkyl chain length. In contrast, with cellulose the amount of Aß removed by the silica beads decreased with increasing alkyl chain length. Cellulose beads with 16 or 22 methylene groups were best (over 99 % removal) among all the beads tested (p ≤ 0.01). The adsorbent surfaces were analyzed by near-infrared spectroscopy, which revealed that the optimum beads had a sufficiently hydrophobic surface with an appropriate amount of adsorbed water accessible on the surface. Aß removal efficiency by C16-cellulose beads was investigated for 5 renal failure patients on hemodialysis, resulting in 51.1 ± 6.6 % for Aß1-40 and 43.8 ± 4.5 % for Aß1-42 (p ≤ 0.01). In conclusion, cellulose beads with 16 or 22 methylene groups and an appropriate amount of adsorbed water were the optimum Aß adsorbents. The device with C16-cellulose beads had high Aß removal activity in humans. These adsorbents might be useful for Alzheimer's disease therapy.

Effects of N-acetyl-L-tryptophan on desorption of the protein-bound uremic toxin indoxyl sulfate and effects on uremic sarcopenia.

INTRODUCTION: Indoxyl sulfate (IS) is a protein-bound uremic toxin that causes uremic sarcopenia. IS has poor dialysis clearance; however, the addition of a binding competitor improves its removal efficiency. METHODS: Dialysis experiments were performed using N-acetyl-l-tryptophan (L-NAT) instead of l-tryptophan (Trp) using pooled sera obtained from dialysis patients. The molecular structures of L-NAT and Trp were similar to that of IS. Therefore, we examined whether Trp and L-NAT were involved in muscle atrophy in the same manner as IS by performing culture experiments using a human myotube cell line. RESULTS: The removal efficiency of L-NAT was the same as that of Trp. However, L-NAT concentrations in the pooled sera increased at the end of the experiment. Trp (1 mM) decreased the area of human myocytes, similar to IS, whereas L-NAT did not. CONCLUSION: L-NAT is a binding competitor with the ability to remove protein-bound IS while preventing sarcopenia.

Dysbiosis of the gut microbiota in children with severe motor and intellectual disabilities receiving enteral nutrition: A pilot study.

BACKGROUND: Children with severe motor and intellectual disabilities (SMIDs) frequently and continuously receive enteral nutrition and medications and lack adequate exercise, which may lead to dysbiosis, an imbalance in the composition of the gut microbiota. However, studies on the composition of gut microbiota in children with SMIDs are limited. Therefore, we aimed to examine the characteristics of the gut microbiota in children with SMIDs. METHODS: 16S rRNA gene sequencing was performed using fecal samples of 10 children with SMIDs, who received enteral nutrition through a gastric fistula or gastric tube (SMID group: median age, 10.0 years), and 19 healthy children (healthy control [HC] group: median age, 9.0 years). Microbial diversity, microbial composition, and abundance of butyric acid-producing bacteria were compared between the groups. Daily dietary fiber intake in the SMID group was evaluated using questionnaires. RESULTS: The Shannon and Simpson indices (alpha diversity indices) were significantly lower in the SMID group than those in the HC group. Beta diversity analysis identified different clusters. Compared with the HC group, Clostridiales and butyric acid-producing bacteria were less abundant and Bacteroidales were more abundant in the SMID group. Dietary fiber intake in the SMID group was approximately two-thirds of the estimated average requirement for healthy Japanese children. CONCLUSION: Children with SMIDs showed dysbiosis with alteration in the microbial diversity, which could partly be attributed to their low dietary fiber intake. Further studies, with the intervention of prebiotics, probiotics, and synbiotics, are warranted to improve dysbiosis in children with SMIDs.

Potential therapeutic system for Alzheimer's disease: removal of blood Aßs by hemodialzyers and its effect on the cognitive functions of renal-failure patients.

The pathological changes of Alzheimer's disease include the deposition of amyloid ß protein (Aß) as senile plaques in the brain. We hypothesized that the rapid removal of Aßs from the blood may act as a peripheral Aß drainage sink from the brain. In this study, the plasma Aß concentrations and the cognitive functions were investigated for in 57 patients on hemodailysis (69.4 ± 3.8 years), 26 renal-failure patients without hemodialysis (66.6 ± 14.7 years), and 17 age-matched healthy controls (66.6 ± 4.1 years). The concentrations of plasma Aßs increased along with the decline of renal functions. Moreover, the renal-failure patients without hemodialysis and with poorer renal functions showed lower cognitive functions. The plasma concentrations of Aß(1-42) correlated with serum creatinine (P < 0.001) and Mini-Mental-State Examination scores (P = 0.017). The dialyzers effectively removed Aßs in the blood during hemodialysis sessions. The plasma Aß concentrations showed steady or slightly decreasing along with duration of hemodialysis. The total amount of Aßs removed during a hemodialysis session was calculated to be comparable to the Aßs dissolved in the blood and the cerebrospinal fluid. The MMSE scores of the hemodialysis patients showed no clear decrease in longer hemodialysis duration. Therefore, the therapeutic approach for Alzheimer's disease by removing Aßs from the blood is worthy of further investigation, including whether or not Aßs in the brain decrease.

First-in-human study of blood amyloid ß removal from early Alzheimer's disease patients with normal kidney function.

INTRODUCTION: Amyloid ß (Aß) is a brain protein that causes Alzheimer's disease (AD). This study aimed to verify whether hemadsorption using a hexadecyl-alkylated cellulose bead (HexDC) column removes blood Aß and brain Aß accumulation in mild cognitive impairment/mild AD cases with normal kidney function. METHODS: Two patients with positive Aß on brain imaging underwent HexDC hemadsorption weekly for 6 months. RESULTS: The Aß removal efficiency of HexDC was 87-99%. Aß1-40 /Aß1-42 influx into the blood in one session was 596/56 and 489/48 ng for Case A and Case B, respectively. Although brain Aß accumulation did not clearly change after 6 months of hemadsorption, cognitive functions measured by the two tests were maintained or slightly improved. CONCLUSION: Blood Aß removal was performed in two early AD patients with normal kidney function without adverse events, and it slightly improved or maintained cognitive function.

Survey of pediatric ward hospitalization due to respiratory syncytial virus infection after the introduction of palivizumab to high-risk infants in Japan.

BACKGROUND: Respiratory syncytial virus (RSV) infection is a major cause of hospitalization during the winter among infants and young children. In 2002 palivizumab was introduced to high-risk infants for RSV hospitalization in Japan. It is important to characterize the hospitalized children due to RSV infection after the introduction of palivizumab. METHODS: A survey was conducted to collect the data from the hospitalized children at 12 participating hospitals during the winter of 2007. RESULTS: From October 2007 through April 2008, 8163 children were admitted to participating hospitals, with RSV infection accounting for 811 of those hospitalizations. Mean age in children with RSV infection at hospitalization was 12.4 ± 12.7 months, and children under 24 months of age accounted for 86.4%. The mean gestational age of those at birth was 38.0 ± 2.6 weeks, with 82.4% of the children born at term. Palivizumab was administered in 24 cases of RSV infection, while there were 28 patients who were not treated with palivizumab, even though they met the indication for palivizumab. Death, in a total of five cases, occurred in children who were not treated with palivizumab. CONCLUSIONS: Palivizumab has been widely used in high-risk infants who were covered by health insurance, and most of the hospitalized children with RSV infection in the study hospitals were not treated with palivizumab.

Prediction of the risk of coronary arterial lesions in Kawasaki disease by brain natriuretic peptide.

Kawasaki disease (KD) is an acute systemic vasculitis associated with the development of coronary arterial lesions (CALs) occurring in 3-5% of children treated by intravenous immune globulin (IVIG). However, a considerable number of patients who are not responding to IVIG are at much higher risk. Although studies have explored potential biomarkers to predict patients with KD who are at risk of CAL, no useful single marker exists. We hypothesized that the serum concentrations of the N-terminal moiety of brain natriuretic peptide (NT-proBNP) can be useful to predict CAL. Forty-three children with KD (29 males and 14 females) were enrolled in this study. Despite IVIG, 6 of the 43 patients developed CAL. There were, however, no significant differences in variables between children with CAL and those without CAL: These include age, gender, day of the illness, leukocyte count, and the serum levels of sodium, C-reactive protein, and albumin. The serum NT-proBNP level was significantly higher in children with CAL than those without CAL (2,611 ± 1,699 vs. 1,073 ± 1,427 pg/ml; P = 0.03): the cutoff value of 1,000 pg/ml to predict CAL produced a specificity of 0.68, sensitivity of 0.83, and an odds ratio as high as 10.4. In conclusion, NT-proBNP is increased in KD patients who are developing CAL, and patients with an elevated serum NT-proBNP >1,000 pg/ml have a risk of CAL ~10 times higher than that of patients with a modest increase.

Evaluation of the performance, operability, and safety of Plasauto µ, a new type of machine for cell-free and concentrated ascites reinfusion therapy, in a postmarketing clinical study.

Cell-free and concentrated ascites reinfusion therapy (CART) is performed by collecting the ascites from the patient, followed by filtration and concentration. Thereafter, concentrated cell-free ascites is reinfused into the patient intravenously. The new type of machine, Plasauto µ, for managing the process of CART was launched onto the market. We have evaluated the machine through postmarketing clinical study in 17 patients with malignant ascites. The amounts of original and concentrated ascites were 3673 ± 1920 g and 439 ± 228 g, respectively. Recovery rates were acceptable regarding values of total protein, albumin, and IgG that were 55.6% ± 17.3%, 60.2% ± 20.8%, and 58.2% ± 20.5%, respectively. Recovery rates were positively associated with amounts of original ascites and negatively associated with total protein concentration. No adverse events related to the machine were observed. The new type of machine showed preferable performance in processing malignant ascites.

Suppression of inflammation during cell-free concentrated ascites reinfusion therapy using a blood purification device.

In recent years, cell-free concentrated ascites reinfusion therapy has been used to treat patients with malignant ascites. However, concentrated ascites reinfusion therapy involves enrichment and reinfusion of useful proteins and inflammatory cytokines. Therefore, fever is a primary side effect and significant problem for patients with ascites. We removed IL-6, an inflammatory cytokine, by mixing malignant ascites and the hexadecyl group adsorbent from a ß2 -microglobulin-adsorbing column (Lixelle S-15). As a result, the hexadecyl group adsorbent did not adsorb the albumin of malignant ascites but adsorbed 43% of IL-6. To investigate the effect of the hexadecyl group adsorbent on hepatocytes, the adsorbed ascites was added to a human hepatoma cell line (HepG2), and the gene expression levels of albumin and serum amyloid A protein were examined. After absorption, ascites showed significantly suppressed serum amyloid A protein expression and significantly increased albumin gene expression compared to before adsorption. Our results suggest that incorporation of Lixelle to filter and concentrate malignant ascites can suppress inflammatory responses and reduce the inhibition of albumin synthesis in the liver after reinfusion.

Expression of tumor necrosis factor receptors on granulocytes in patients with myeloperoxidase anti-neutrophil cytoplasmic autoantibody-associated vasculitis.

BACKGROUND/AIMS: To clarify the clinical significance of tumor necrosis factor (TNF) receptors in patients with myeloperoxidase (MPO)-anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, we evaluated the cell surface expression of TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2). PATIENTS AND METHODS: 43 patients with MPO-ANCA-associated vasculitis, 16 patients with chronic renal failure, 10 patients with sepsis, 15 patients with systemic lupus erythematosus, and 18 healthy controls were enrolled in this study, and the surface expression levels of TNFR1, TNFR2, CD63, and CD64 on granulocytes were assessed. In 21 patients with MPO-ANCA-associated vasculitis, soluble TNFR1 (sTNFR1), soluble TNFR2(sTNFR2), and TNF-alpha in the serum were also measured. RESULTS: The surface expression levels of TNFR1 and TNFR2 on granulocytes were significantly higher in patients with MPO-ANCA-associated vasculitis than in the healthy controls, and positively correlated with the Birmingham Vasculitis Activity Score (BVAS). The levels of sTNFR1, sTNFR2, and TNF-alpha in the serum were also significantly higher in patients with MPO-ANCA-associated vasculitis than in the healthy controls. Serum levels of sTNFR1 and sTNFR2 correlated with serum creatinine, while the surface expression of TNFR1 and TNFR2 on the granulocytes did not. There was no significant correlation between the BVAS and CD63 or BVAS and CD64. CONCLUSION: The surface expression levels of TNFR1 and TNFR2 on granulocytes were upregulated in patients with MPO-ANCA-associated vasculitis and reflected disease activity.

Cerebral blood flow monitoring using a novel laser Doppler flowmeter in asphyxiated infants.

BACKGROUND: The aim of the present study was to investigate the role of early changes in cerebral blood flow (CBF) predicting the severity of neurological outcome in asphyxiated infants. METHOD: Serial monitoring of CBF was performed using a newly developed laser Doppler flowmeter (LDF) in parallel with conventional hemodynamic monitoring, such as mean arterial blood pressure (mABP) or heart rate (HR) in 11 asphyxiated infants (five infants with neurological sequelae and six infants without sequelae) during the first 4 days of life. Psychomotor development was followed up to 20 months. RESULTS: No differences in average CBF, mABP, average HR, or Apgar scores were found between infants with neurological sequelae and those without (P > 0.1). Significant difference was found only in average stability index during the first 48 h of life (SI48), defined as a coefficient of variation of CBF during the corresponding period (P= 0.04). An SI48 > or = 0.24 had positive predictive value of 100% for neurological sequelae while that <0.24 had a negative predictive value of 66.7%. CONCLUSION: SI48, an average stability index of CBF during the first 48 h of life, can be a useful index to predict neurological outcome in asphyxiated infants.