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Tomoyuki Yokota,
Ichiro Morioka,
Takayuki Kodera,
Takeshi Morisawa,
Itsuko Sato,
Seiji Kawano,
Tsubasa Koda,
Kiyomi Matsuo,
Kazumichi Fujioka,
Satoru Morikawa,
Akihiro Miwa,
Akio Shibata,
Naoki Yokoyama,
Masahiko Yonetani,
Hideto Yamada, Hajime Nakamura,
Kazumoto Iijima
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ABSTRACT: BACKGROUND: Serum unbound bilirubin (UB) level measures bilirubin not bound to albumin, and has been reported to be better than total bilirubin level at identifying infants at risk of developing bilirubin-induced neurotoxicity, including auditory abnormalities. A detailed treatment strategy for newborns with high serum UB levels has not been established. Our objective was to assess auditory outcomes in newborns with serum UB levels of ≥1.00 μg/dL who were treated according to our novel treatment protocol. METHODS: A prospective clinical study was conducted in newborns weighing >1,500 g with serum UB levels of ≥1.00 μg/dL who were admitted to Kobe University Hospital and Kakogawa Municipal Hospital, Japan from 2006 to 2011. Enrolled newborns were treated as follows: (1) if the serum UB level was 1.00-1.50 μg/dL, phototherapy and infusion were administered with or without albumin or immunoglobulin therapy; and (2) if the serum UB level was >1.50 μg/dL, exchange transfusion was performed immediately. Auditory brainstem responses were evaluated at the time of discharge. RESULTS: A total of 89 Japanese newborns with UB levels of ≥1.00 μg/dL were enrolled at a median age of 4 days. Of these, 85 had UB levels of 1.00-1.50 μg/dL and four had UB levels of >1.50 μg/dL. After being treated according to our protocol, no newborns were diagnosed with auditory brainstem response abnormalities. CONCLUSIONS: Our treatment protocol for Japanese newborns with serum UB levels of ≥1.00 μg/dL may be useful for the prevention of bilirubin-induced auditory abnormalities.
Pediatrics International 09/2012; · 0.63 Impact Factor
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Akihiro Miwa,
Ichiro Morioka,
Tomoyuki Yokota,
Akio Shibata,
Kiyomi Matsuo,
Kazumichi Fujioka,
Tsubasa Koda,
Satoru Morikawa,
Hisahide Nishio,
Naoki Yokoyama, Hajime Nakamura,
Masafumi Matsuo,
Hideto Yamada
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ABSTRACT: Free bilirubin concentration (B(f)) is an index for identifying newborns at risk for developing bilirubin-induced neurotoxicity. It has been suggested that B(f) measured by a single peroxidase concentration (B(f-single)) does not equal the equilibrium concentration of B(f), which is confirmed by B(f) at two different peroxidase concentrations (B(f-two)). However, the differences between B(f-single) and B(f-two) are unknown in the serum of term or late-preterm newborn infants. Furthermore, to apply B(f-single) with savings on time and cost to the clinical setting, it is very important for us to clarify the differences between B(f-single) and B(f-two).
Forty serum samples were obtained from 21 term or late-preterm newborns who were admitted at Kobe University Hospital. Using a peroxidase method, B(f-single) was measured at one peroxidase concentration, and B(f-two) was determined at two different peroxidase concentrations (the manufacturer's recommended peroxidase concentration and half the manufacturer's recommended peroxidase concentration). To clarify the relationship between B(f-single) and peroxidase concentrations, B(f-single) was measured at five different concentrations of peroxidase reagent. Intra-day and inter-day analyses were performed to assess the precision of B(f-single) and B(f-two).
1/B(f-single) increased as peroxidase concentration increased. B(f-single) was significantly lower than B(f-two) (B(f-single): 0.50 microg/dL [0.13 - 1.22 microg/dL] versus B(f-two): 0.59 microg/dL [0.15 - 1.76 microg/dL], p < 0.001), but B(f-single) was significantly correlated with B(f-two) (r = 0.953, p < 0.0001). Intra-day analysis showed that the CV was 9.7% for B(f-two) and 3.3% for B(f-single), and the inter-day CV was 12.4% for B(f-two) and 3.2% for B(f-single).
Although B(f-single) and B(f-two) are not identical, B(f-single) is significantly correlated with B(f-two) and it is more precise than B(f-two) in term or late-preterm newborns.
Clinical laboratory 01/2012; 58(5-6):507-14. · 0.90 Impact Factor
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ABSTRACT: The clinical presentations of head trauma due to falls among young children aged less than 2 years are controversial, particularly in Japan, as the history of trauma recounted by a caretaker is not always reliable. The purpose of this study was to assess the validity of caregiver's reports on head trauma due to falls in young children aged less than 2 years in Japan.
All patients <2 years of age presenting with head trauma resulting from a fall who were admitted to 3 children's hospitals in Japan from January 2001 to December 2005 were retrospectively reviewed (N = 58). The clinical presentations were compared among groups categorized by the heights from which the patient fell (short (≤120 cm) or long (>120 cm)) and the surface on which the patient landed (carpet, tatami (Japanese mattress), hardwood floor, or concrete).
Patients who suffered short falls were more likely to present with subdural hemorrhage (SDH) than those who suffered long falls (74% and 40%, respectively, P = 0.027). More specifically, 62% of short falls showed SDH indicative of shaken baby syndrome (e.g. multilayer SDH). Neurological symptoms, cyanosis, and SDH were more commonly observed in patients who landed on carpeted or tatami surfaces than in those who landed on hardwood or concrete floors.
Short falls and landing on soft surfaces resulted in the presentation of severer clinical symptoms than did long falls and landing on hard surfaces, suggesting that the validity of caretakers' reports on infant or young children's head trauma due to falls is low. Further research is warranted to investigate the cause of infant head trauma due to falls.
Clinical medicine insights. Pediatrics. 01/2010; 4:11-8.
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ABSTRACT: Background: The aim of the present study was to evaluate the value of an end-tidal carbon monoxide corrected for inhaled carbon monoxide concentration (ETCOc) at the early neonatal period. The value would be useful for predicting subsequent hyperbilirubinemia in non-hemolytic full-term infants.Methods: The ETCOc levels were measured every 6 h during the first 72 h of life in healthy, full-term, non-hemolytic, newborn Japanese infants using a breath carbon monoxide analyzer. The ETCOc levels in hyperbilirubinemic infants were compared with those in non-hyperbilirubinemic infants. Hyperbilirubinemia was defined as the level of the peak total serum bilirubin concentration (TBC) greater than or equal to 257 μmol/L (15.0 mg/dL). The ETCOc measurement for predicting subsequent hyperbilirubinemia was evaluated with a receiver–operating characteristic (ROC) curve.Results: Fifty-one infants were enrolled in the study. Seven of the 51 infants developed hyperbilirubinemia. The ETCOc levels in non-hyperbilirubinemic infants were decreased in the first 72 h after birth. However, those in the hyperbilirubinemic infants were not decreased significantly, and were higher than those in non-hyperbilirubinemic infants at 42, 48, 54 and 66 h of age. The ETCOc level at 42 h of age was the most predictive of subsequent hyperbilirubinemia by ROC analysis. At the cut-off level of 1.8 μL/L (p.p.m.), the sensitivity, the specificity, the positive predictive value and negative predictive value were 86, 80, 40 and 97%, respectively.Conclusion: Increased ETCOc level in the early neonatal period is associated with subsequent hyperbilirubinemia, even in infants without hemolytic disease. The ETCOc measurement may be useful as a screening test for predicting hyperbilirubinemia without hemolytic diseases.
Pediatrics International 07/2008; 43(4):329 - 333. · 0.63 Impact Factor
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Keiko Wada,
Atsuko Takeuchi,
Kayoko Saiki,
Retno Sutomo,
Hans Van Rostenberghe,
Narazah Mohd Yusoff,
Vichai Laosombat,
Ahmad Hamim Sadewa,
Norlelawati Abdul Talib,
Surini Yusoff,
Myeong Jin Lee,
Hitoshi Ayaki, Hajime Nakamura,
Masafumi Matsuo,
Hisahide Nishio
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ABSTRACT: Mutations in the gene encoding UDP-glucuronosyltransferase 1A1 (UGT1A1) may reduce the glucuronidation of estradiol, bilirubin, etc. In the present study, we used a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method to assay the activities of recombinant mutated UGT1A1 toward 17beta-estradiol (E2), by determining its glucuronide (E2G) content. Direct evidence for glucuronide formation was provided by E2G-specific ion peaks. The UGT1A1 activities of G71R (exon 1), F83L (exon 1), I322V (exon 2) and G493R (exon 5) mutants were 24, 30, 18 and 0.6% of the normal UGT1A1 activity, respectively. In conclusion, our study showed that LC/MS/MS enabled accurate evaluation of the effects of mutations on recombinant UGT1A1 activity towards E2.
Journal of Chromatography B 07/2006; 838(1):9-14. · 2.89 Impact Factor
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Pediatrics International 07/2005; 47(3):343-7. · 0.63 Impact Factor
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ABSTRACT: Periventricular cysts are not rare findings in neonates. However, they are sometimes associated with serious clinical complications, such as congenital viral infections and anomalies.
We performed a retrospective follow-up study on newborns who had periventricular cysts on routine cranial ultrasound examination.
We followed 13 infants (three preterm) with periventricular cysts. Ten had single or multiple germinolysis cysts and the remaining three had choroid plexus cysts. All infants had various kinds of underlying complications, including congenital viral infection (two with cytomegalovirus and one with rubella),Sotos syndrome (n = 4), intrauterine growth retardation (n = 5), large-for-dates(n = 4), congenital heart disease (n = 1),myelomeningocele (n = 1) and other minor anomalies. All cases of germinolysis except for one developed a neurodevelopmental abnormality and/or delay. In contrast,all three cases with choroid plexus cysts appeared to develop well,despite the underlying complications.
Germinolysis cysts seem to be associated with systemic diseases and should be treated as a high-risk sign for impaired neurological development.
Pediatrics International 01/2004; 45(6):692-6. · 0.63 Impact Factor
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ABSTRACT: In the neonatal intensive care unit (NICU), hemodynamics in very low-birthweight infants are generally examined for oxygen saturation (SpO2), heart rate, respiration rate, and blood pressure. The present study examined how changes in cerebral circulation in preterm infants can be evaluated by the SpO2 monitoring method with near infrared spectroscopy (NIRS) to detect the cerebral circulation.
The study was conducted in 11 low-birthweight neonates with a mean weight of 1252 g (940-1948 g), mean post-conceptional age of 28.9 weeks (28-31 weeks) and in whom a total of 145 apneic episodes were examined. Changes in cerebral circulation at the apneic attack were evaluated by two parameters of Delta HbD ( micro mol/L) for reduction in cerebral oxygenation and Delta cHb (mL/100 g brain) for variation in cerebral blood volume using the near infrared spectroscopy (NIRS).
There was a tendency for a reduction in cerebral oxygenation and a change in cerebral blood volume as SpO2 was reduced. In the event of apneic attacks where SpO2 was reduced to <85%, cerebral oxygen saturation was extensively reduced. In addition, cerebral blood volume was also greatly changed when the SpO2 was reduced to <85%, and changed further still when SpO2 was reduced again to < or =75%.
Reduction in SpO2 (<85%) was suggested to be an effective indication to changes in cerebral circulation. In the case of apneic attacks where SpO2 was < or =85%, the cerebral circulation in preterm low-birthweight neonates was extensively changed and, therefore, attention should be paid to changes in the concentration of SpO2 when managing apnea of prematurity in NICU.
Pediatrics International 12/2003; 45(6):661-4. · 0.63 Impact Factor
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ABSTRACT: We tested whether the entire soluble extracellular domain of the human transforming growth factor-beta (TGF-beta) type II receptor, fused to the Fc portion of human immunoglobulin G (IgG1) (Tbeta-ExR) and expressed in skeletal muscles by adenovirus-mediated gene transfer (AdTbeta-ExR), can ameliorate renal dysfunction and histologic progression in a rat experimental anti-glomerular basement membrane (GBM) nephritis.
Anti-GBM nephritis was induced in Wistar Kyoto rats by an intravenous injection of anti-rat glomerular basement membrane (GBM) sera. At day 1 (24 hours after induction), AdTbeta-ExR (1 x 109 pfu/mL) was injected into the femoral muscle in the treatment group, and an adenovirus vector-expressing bacterial beta-galactosidase (AdLacZ) was injected into the control group. Then, clinical and histologic changes were examined for 3 weeks after the induction of anti-GBM nephritis.
Tbeta-ExR was detected in the serum at day 7, but the serum concentration of Tbeta-ExR had decreased below the detectable level by day 14. Although blood pressure and the degree of proteinuria were similar in both groups, the deterioration of renal function was significantly blunted in the treatment group. Crescent formation and interstitial fibrosis were also ameliorated in the treatment group. These histologic improvements were accompanied by the decreased interstitial infiltration of macrophages and the decreased alpha-smooth muscle actin (alpha-SMA)-positive cells in the glomeruli and the interstitium.
This study demonstrated for the first time that the blockade of TGF-beta action by AdTbeta-ExR in the early stage of anti-GBM nephritis ameliorates the clinical and histologic progression. In addition, this study shed light on the development of a specific gene therapy for human crescentic glomerulonephritis.
Kidney International 08/2003; 64(1):92-101. · 6.61 Impact Factor
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ABSTRACT: Blockade of TGF- action ameliorates renal dysfunction and histologic progression in anti-GBM nephritis.Background We tested whether the entire soluble extracellular domain of the human transforming growth factor- (TGF-) type II receptor, fused to the Fc portion of human immunoglobulin G (IgG1) (T-ExR) and expressed in skeletal muscles by adenovirus-mediated gene transfer (AdT-ExR), can ameliorate renal dysfunction and histologic progression in a rat experimental anti-glomerular basement membrane (GBM) nephritis.
Kidney International 06/2003; 64(1):92-101. · 6.61 Impact Factor
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ABSTRACT: Intron 2 of the dystrophin gene is unusually large, extending 157 kb on the X-chromosome, and is known to contain one cryptic exon 2a. Here, we report that a single nucleotide change in the middle of this huge intron is a source of two novel extra exons. A novel point mutation changing T to A nucleotide was identified at 5591 bp downstream from the 3' end of exon 2 (T310+5591A) in genomic DNA of an asymptomatic dystrophinopathy case. The mutation identification was initiated by detection of two novel dystrophin mRNAs containing a 132-nucleotide or 46-nucleotide insertion between exons 2 and 3 in lymphocytes but one with a 132-nucleotide insertion in skeletal muscle. It was concluded that T310+5591A created a novel consensus sequence for a splice acceptor site leading to the formation of two novel exon structures by using two cryptic splice donor sites at 132 bp or 46 bp downstream. The former maintained the dystrophin reading frame and was expected to insert 44 amino acids in the N-terminal domain of dystrophin, whereas the latter created a premature stop codon. An immunohistochemical study of the skeletal muscle of the patient disclosed that the N-terminal domain of dystrophin was not stained, but the rod- and C-terminal domains were stained in a patchy and discontinuous manner, indicating that the in-frame mRNA was functional. Creation of a splice acceptor site by a single nucleotide change leading to extra exon structures is a novel molecular mechanism in human disease.
Human Genetics 03/2003; 112(2):164-70. · 5.07 Impact Factor
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ABSTRACT: We hypothesized that selective brain hypothermia (SBHT) decreases production of hydroxyl radicals (*OH) induced by hypoxia-ischemia (H-I) and reperfusion and attenuates neuronal damage in neonatal rat brain. Anesthetized 7-day-old rats were divided into a normothermia (NT) group (n=6) and a SBHT group (n=7) and subjected to 90-min H-I, followed by a 90-min recovery period. Brain temperature (BT) was regulated by a water-cooled metallic plate placed under the head. The BT of the SBHT group was set at 31.0+/-1.0 degrees C during the H-I and recovery period. Microdialysis and the salicylate-trapping method were used to detect *OH in the striatum. Neuronal damage was quantified by counting the surviving neurons at 120 hr after reperfusion. The NT group had significant increases in 2,3-dihydroxybenzoic acid (DHBA) (223+/-166%) and 2,5-DHBA (321+/-153%) above baseline levels. The increases in 2,3-DHBA (127+/-40%) and 2,5-DHBA (133+/-33%) were significantly lower (p < 0.01) in the SBHT group. The number of surviving neurons was decreased significantly in the NT group but not in the SBHT group. We conclude that SBHT reduces *OH production during H-I and reperfusion and has protective effects against neuronal damage.
The Kobe journal of medical sciences 02/2003; 49(3-4):83-91.
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ABSTRACT: To confirm the accuracy and precision of transcutaneous bilirubin (TcB) values measured by a new device with two optical paths (JM-103) and the value of total serum bilirubin (TSB) level in clinical units of measurement.
For comparison of the levels of accuracy and precision of JM-103 and the old device (JM-102), serum samples were collected from 77 Japanese infants in three different hospitals including 24 preterm infants and 53 term infants. Measurement of TcB by JM-103 and JM-102 were performed on the forehead of each infant within 30 min before or after blood sampling.
The range of TSB was limited to 19.6 mg/dL and to 17 mg/dL for preterm infants. The correlation coefficients for all subjects (r = 0.94) and for term and preterm subjects between TcB measured by JM-103 and TSB was higher than that between TcB measured by JM-102 and TSB. The regression line in term infants between TcB measured by JM-103 and TcB was similar to that in preterm infants. The error distribution of TcB measured by JM-102 and TSB for all subjects (0.00 +/- 2.21) and for term and preterm subjects was larger than that of TcB measured by JM-103 and TSB (all subjects, 0.30 +/- 1.55).
Journal of Perinatal Medicine 02/2003; 31(1):81-8. · 1.70 Impact Factor
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ABSTRACT: A retrospective analysis of the clinical features of 62 patients with various hematological or other diseases who received allogeneic stem cell transplantation (SCT) between April 1990 and July 2002 in the Department of Pediatrics, Kobe University Hospital was conducted to investigate prognostic factors of allo-SCT. Among 62 allo-SCT, 51 (82%) were bone marrow transplantation (BMT), 5 (8%) were peripheral blood stem cell transplantation and 6 (10%) were cord blood transplantation. Disease-free survival rate (DFS) estimated according to the diagnosis group did not show any significant difference. For hematological malignant diseases, DFS estimated according to the disease stage was 66.7% for the patients in the standard stage and 30.0% for the patients in the advanced stage (p=0.0249). Of 47 evaluable patients receiving allo-BMT, DFS of patients receiving the last transfusion of platelets on or before day 21 was significantly higher than that of patients receiving the last transfusion after day 21 (66.7% vs 34.8%, p=0.0111). These results demonstrate that more appropriate indications and points for SCT should be applied to patients in the advanced stage, and that whether the last transfusion of platelet is on or before or after day 21 is an important prognostic factor for allo-BMT because the necessity for platelet transfusion was vividly reflected in the status of the patients.
The Kobe journal of medical sciences 02/2003; 49(1-2):1-10.
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ABSTRACT: The molecular background of an intermediate type of dystrophinopathy [Duchenne and Becker muscular dystrophy (DMD/BMD)] remains to be clarified, and out-of -frame and in-frame mutations of the dystrophin gene are shown to be causes of DMD and BMD, respectively. In a boy with this disease, dystrophin mRNA extracted from lymphocytes and muscle were analyzed both qualitatively and quantitatively using reverse transcription PCR. Three different dystrophin mRNA were found to be produced via the use of three cryptic splice acceptor sites resulting from a novel point mutation of 2831-2A>G at the conserved splice acceptor site of intron 20. One of three mRNA showed an insertion of six nucleotides of intron 20 between exons 20 and 21 (dys+6) that encoded two novel amino acids in the rod domain of dystrophin. Two other mRNA species showed an insertion of seven nucleotides of intron 20 between exons 20 and 21 (dys+7) or a seven-nucleotide deletion in exon 21 (dys-7). Quantitative analysis of each dystrophin mRNA expressed in the boy's skeletal muscle disclosed that around 95% and 5% of dystrophin mRNAs were dys-7 and dys+6, respectively, whereas these two mRNA were almost equally expressed in lymphocytes. It is suggested that production of a small fraction of in-frame mRNA in muscle explains the molecular background of the intermediate type of dystrophinopathy in the index case. This finding underlines the potential of genetic therapeutic strategies aimed to modify mRNA in DMD to generate a much milder disease.
Pediatric Research 01/2003; 53(1):125-31. · 2.70 Impact Factor
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ABSTRACT: We report for the last 1 year and 9 months results of the molecular diagnosis of Duchenne (DMD) and Becker (BMD) muscular dystrophy at Kobe University. Analysis was done on 87 patients belonging to 76 families (66 DMD cases, 10 BMD cases). We first determined the presence of deletions or duplications using Southern blot analysis. Then analyzed small mutations (point mutations or small deletions/insertions) by mRNA analysis using RT-PCR and direct sequencing. 69 mutations (89.5%) were found, 46 deletions (60.5%), 5 duplications (6.6%) and 17 point mutations (22.4%) including 15 nonsense mutation. mRNA analysis from lymphocytes or muscle was useful for screening patients without a mutation identifiable by Southern blot analysis.
No to hattatsu. Brain and development 10/2002; 34(5):391-7.
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ABSTRACT: Gilbert's syndrome is a common inherited disorder of bilirubin metabolism contributing to the development of neonatal jaundice and causing recurrent jaundice after the neonatal period. In the patients with Gilbert's syndrome, mutations have been reported in the promoter and exons of the uridine diphosphate-glucuronosyl transferase 1 (UGT1A1) gene on chromsome 2q37, which encodes bilirubin uridine diphosphate-glucuronosyltransferase. However, the genetic basis of Gilbert's syndrome, including its inheritance trait, remains to be clarified.
Patients 1 and 2 were Thai sisters with Gilbert's syndrome. They had a history of prolonged neonatal jaundice and showed recurrent jaundice after their infancy, while the parents showed no symptoms. To search for the mutation in the patients, all exons of the UGT1A1 gene were amplified by polymerase chain reaction (PCR) and sequenced directly. The frequency of the mutation in controls was studied by PCR-restriction enzyme digestion method.
The patients were homozygous for a novel single transition of T to C at nucleotide position 247 (exon 1), which would predict a substitution of leucine for phenylalanine at codon 83 of the enzyme protein. No other mutation was detected in any regions except exon 1. The parents with no symptoms showed heterozygosity for the mutation. Among the 110 Japanese controls, no homozygous individuals and three heterozygous individuals for the mutation were identified, giving a mutated allele frequency of 0.0136.
A novel missense mutation in the UGT1A1 gene was identified in two Thai siblings with Gilbert's syndrome. The affected family showed that homozygosity for the mutation may lead to apparent symptoms and that the syndrome was inherited as an autosomal recessive trait. The mutation does not explain a high incidence of neonatal jaundice in Japan, because it is very rare in the Japanese population.
Pediatrics International 09/2002; 44(4):427-32. · 0.63 Impact Factor
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ABSTRACT: The serum bilirubin level of Japanese newborn infants in their first few days is significantly higher than that in Caucasian newborn infants, suggesting that there might be genetic risk factors for the development of neonatal hyperbilirubinemia in the Japanese population. Recently, it has been reported that a variant TATA box in the promoter region of the bilirubin UDP-glucuronosyltransferase 1 (UGT1A1) gene is associated with the development of neonatal hyperbilirubinemia. This finding led us to the idea that a mutation, glycine to arginine at codon 71 (G71R), in the coding region of the UGT1A1 gene can cause neonatal hyperbilirubinemia. In this study, we determined the genotypic distribution of the G71R mutation in 72 Japanese newborn infants: 23 infants with hyperbilirubinemia and 49 infants without hyperbilirubinemia. In the hyperbilirubinemia group, 15 of 23 newborn infants had the G71R mutation (3 homozygotes and 12 heterozygotes), whereas in the non-hyperbilirubinemia group 16 of 49 newborn infants had the G71R mutation (1 homozygote and 15 heterozygotes). Therefore, the G71R mutation was present significantly more frequently in the hyperbilirubinemia group than in the non-hyperbilirubinemia group. This finding strongly suggests that the presence of the G71R mutation contributes to the development of neonatal hyperbilirubinemia in the Japanese population.
The Kobe journal of medical sciences 09/2002; 48(3-4):73-7.
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ABSTRACT: Cyclosporine (CsA) is effective for the treatment of children with steroid-dependent and -resistant nephrotic syndrome (NS), but it can result in chronic CsA nephrotoxicity including CsA-induced tubulointerstitial lesions. The factors responsible for the development of CsA-induced tubulointerstitial lesions are unknown.
To identify the risk factors for the development of CsA-induced tubulointerstitial lesions in children with minimal change NS who had been treated with long-term moderate-dose CsA, we compared several clinical and laboratory factors of 37 patients with and without CsA-induced tubulointerstitial lesions by the Mann-Whitney U test, Fisher's exact test, and stepwise logistic-regression analysis.
Thirteen patients had CsA-induced tubulointerstitial lesions and 24 patients had none. Among clinical and laboratory factors, the duration of CsA treatment (P = 0.003) and the duration of heavy proteinuria during CsA treatment (P = 0.024) were related to the development of CsA-induced tubulointerstitial lesions as determined by the univariate analyses. Indeed, CsA-induced tubulointerstitial lesions were found in 2 of 18 (11%) patients who had been treated with CsA for less than 24 months, but in 11 of 19 patients (58%) who had been treated for more than 24 months (P = 0.005). They were also found in 4 of 23 patients (17%) who had heavy proteinuria for less than 30 days during CsA treatment, but in 9 of 14 patients (64%) who had heavy proteinuria for more than 30 days (P = 0.006). Stepwise logistic-regression analysis revealed that the duration of CsA treatment for more than 24 months (chi2 = 6.203, P = 0.013) and the duration of heavy proteinuria during CsA treatment for more than 30 days (chi2 = 5.871, P = 0.015) were independent risk factors for the development of CsA-induced tubulointerstitial lesions.
Duration of the CsA treatment and the duration of heavy proteinuria during CsA treatment were independent significant risk factors for the development of CsA-induced tubulointerstitial lesions in children with MCNS who had been treated with long-term moderate-dose CsA.
Kidney International 06/2002; 61(5):1801-5. · 6.61 Impact Factor
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ABSTRACT: Spinal muscular atrophy (SMA) is one of the most common autosomal recessive disorders characterized by degeneration of anterior horn cells in the spinal cord, and leads to progressive muscular weakness and atrophy. At least three SMA-related genes have been identified: SMN1, NAIP and p44t. We analyzed these genes in 32 SMA patients and found that the SMN1 gene was deleted in 30 of 32 patients (94 %), irrespective of clinical type. The NAIP gene was deleted in 6 patients and its deletion rate was higher in type I patients than that in type U or V. Further, in type I patients lacking the NAIP gene, deterioration in their respiratory function is more rapid than in those type I patients retaining the NAIP gene. Since complete p44t deletion was observed in only 3 patients, the correlation between the p44t deletion and severity of SMA remained ambiguous. We concluded that the NAIP deletion was closely related to the clinical severity of SMA and was a predictive marker of SMA prognosis, while the SMN1 deletion did not correlate with clinical severity.
The Kobe journal of medical sciences 05/2002; 48(1-2):25-31.
