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Biomedical subjects

K Kidouchi

Publications and source records attributed to K Kidouchi.

At least 19 recordsLinked to original sources
PubMed2003

Allopurinol challenge tests performed before and after living-related donor liver transplantation in citrullinaemia.

We performed allopurinol challenge tests to evaluate the metabolic state of a citrullinaemic patient who received a living-relative donor liver transplant. Before transplantation, large amounts of orotic acid and orotidine were excreted during the challenge test. Following transplantation, excretion of these compounds in response to allopurinol was normalised. The challenge test was a safe and useful method to evaluate the metabolic state of the patient.

Allopurinol↗
PubMed2000

Urinary pyrimidine analysis in healthy newborns, infants, children, adults and patients with congenital metabolic diseases.

BACKGROUND: In previous reports, the reference range for urinary pyrimidine was determined on the basis of a small number of samples, with data for only a few patients being reported. In the present study, we measured urinary pyrimidine compounds in 25 healthy newborns, 33 healthy infants, 130 healthy children and 166 healthy adults. In addition, we also analyzed urinary pyrimidine compounds in various patients with abnormal pyrimidine metabolism, such as congenital pyrimidine metabolism disorders and urea cycle disorders. METHODS: We analyzed urines by high-performance liquid chromatography with column switching. Analyses were performed with both a reverse-phase column and an anion-exchange column. The columns were connected by a column switch, with all systems being controlled automatically by a computerized system controller. RESULTS: The excretion of pyrimidine compounds in patients with abnormal pyrimidine metabolism (containing heterozygotes) was out of our reference ranges. CONCLUSIONS: These results suggest that urinary pyrimidine analysis is a useful index for the diagnosis of pyrimidine metabolism disorders, urea cycle disorders and these heterozygotes. Based on this large-group analysis of healthy individuals, we were able to determine the reference ranges of urinary orotic acid, dihydrouracil and uracil for each age group.

Adolescent↗
PubMed2000

Screening for pyrimidine metabolism disorders using dried filter-paper urine samples: method development and a pilot study in Nagoya City, Japan.

A screening system for pyrimidine metabolism disorders by measurement with high-performance liquid chromatography using dried filter-paper urine samples is presented. This system permits the simultaneous determination of dihydrouracil, uracil, orotic acid and pseudouridine. The coefficient of variations for the four compounds on the filter-paper urine samples were 0.010 approximately 0.069 and the recoveries were 98.5 approximately 107.1%. The detection limits of the four compounds were 2 approximately 20 micromol/liter. The correlation between the filter-paper urine samples and liquid urine samples was excellent (0.938-0.988). We supeculated that this method could be used to detect pyrimidine metabolism disorders, such as dihydropyrimidinuria, dihydropyrimidine dehydrogenase deficiency and hereditary orotic aciduria. As a pilot study, we have analyzed dried filter-paper urine samples from 34, 200 healthy Japanese, and found three cases of dihydropyrimidinuria without clinical symptoms.

Drug Stability↗
PubMed2000

Detection of ornithine transcarbamylase deficiency heterozygotes by measuring of urinary uracil.

The importance of detecting heterozygosity for X-linked ornithine transcarbamylase deficiency is well known. Although the DNA analysis and the allopurinol loading tests are commonly used for this purpose, both methods require complicated procedures. In order to establish a simple test for detecting female heterozygotes, we examined the uracil and orotic acid in single-voided urine samples from 70 healthy women, and from 12 asymptomatic females with ornithine transcarbamylase deficiency. Based on the results of healthy women, we were able to determine a screening cut-off line of 11.9 micromol/mmol creatinine (mean +/- 1SD in logarithmic form) for uracil. Using this cut-off line, the sensitivity of OCT heterozygotes was 100%. We were also able to establish a second cut-off line of 28.9 micromol/mmol creatinine (mean +/- 3SD in logarithmic form) for diagnosis. Using this second cut-off line, the specificity of OCT heterozygotes was 100%. Our study has shown that the measurement of urinary uracil is a relatively simple and effective method for detecting female heterozygotes.

Female↗
PubMed1999

Automated determination of 5-fluorouracil and its metabolite in urine by high-performance liquid chromatography with column switching.

We report a quantitative assay of 5-fluorouracil (FU) and its metabolite, 5-fluorodihydrouracil (FDHU) in human urine by used a column-switching high-performance liquid chromatographic method. The analyses were carried out using a molecular exclusion column for sample purification, and a cation-exchange column for separation. Each sample required only 40 min to analyze, and required no preparation other than filtration. Linearity was verified up to 1000 nmol/ml (r > 0.993). The recovery of FU was 96-101%; recovery of FDHU was 96-105%. The imprecision (RSD) for FU (10-100 nmol/ml) was < 1.5%, same-day (n = 5), and < 1.8%, day-to-day (n = 5). The imprecision (RSD) for FDHU (10-100 nmol/ml) was < 3.2%, same-day (n = 5), and < 4.0%, day-to-day (n = 5). The detection limits were, respectively, 0.1 nmol/ml. We measured FU and FDHU in urine of seven cancer patients after oral administration of FU. The cumulative quantity ratio of the FDHU and FU (FDHU/FU) excreted in their urine within 120 min after FU administration was a constant value in all seven patients. Based on these results, we believe that our method provides a useful tool for evaluating FU metabolism.

Breast Neoplasms↗
PubMed1998

Population and family studies of dihydropyrimidinuria: prevalence, inheritance mode, and risk of fluorouracil toxicity.

To evaluate the prevalence of dihydropyrimidinuria (DHPuria), we analyzed urine samples from 21,200 healthy Japanese infants, and found two cases of DHPuria without clinical symptoms. Based on this result, we estimated the prevalence to be approximately 1/10,000 births in Japan. In addition, we analyzed pyrimidine catabolism on a previously reported family with an adult DHPuria case. We newly identified the sister of the propositus as the second case of DHPuria in this family, because she excreted large amounts of dihydrouracil and dihydrothymine. The parents and the child of the propositus showed slight increases of dihydrouracil and dihydrothymine. This is the first family with 2 cases of DHPuria, indicating that DHPuria is an inherited condition. To determine the inheritance of DHPuria in this family and to examine the risk of 5-fluorouracil (5-FU) toxicity, a uracil loading test was performed on the parents. Urinary dihydrouracil concentrations in the parents after the loading were several times higher than those in normal control persons, the finding being consistent with DHPuria heterozygotes. This, along with data on the propositus, his sister, and his child, indicates that DHPuria is an autosomal recessive condition. In addition, DHPuria homozygotes may have a high risk of 5-FU toxicity, while the risk is relatively low in heterozygotes.

Adult↗
PubMed1998

Dihydropyrimidinase deficiency: structural organization, chromosomal localization, and mutation analysis of the human dihydropyrimidinase gene.

Dihydropyrimidinase (DHP) deficiency (MIM 222748) is characterized by dihydropyrimidinuria and is associated with a variable clinical phenotype. This disease might be associated with a risk of 5-fluorouracil toxicity, although no cases have been reported. We present here both the molecular characterization of the human DHP gene and, for the first time, the mutations causing DHP deficiency. The human DHP gene spans >80 kb and consists of 10 exons. It has been assigned to 8q22, by FISH. We performed mutation analysis of genomic DNA in one symptomatic and five asymptomatic individuals presenting with dihydropyrimidinuria. We identified one frameshift mutation and five missense mutations. Two related Japanese adult subjects were homozygous for the Q334R substitution, whereas two other, unrelated Japanese infant subjects were heterozygous for the same mutation, but this mutation is not common in the Japanese population. A Caucasian pediatric patient exhibiting epileptic attacks, dysmorphic features, and severe developmental delay was homozygous for W360R. Using a eukaryotic expression system, we showed that all mutations reduced enzyme activity significantly, indicating that these are crucial DHP deficiency-causing mutations. There was no significant difference, in residual activity, between mutations observed in the symptomatic and those observed in the asymptomatic individuals.

Adult↗
PubMed1998

Hereditary orotic aciduria heterozygotes accompanied with neurological symptoms.

We report a family with hereditary orotic aciduria heterozygotes. A 3-year-old boy who had been diagnosed as having cerebral palsy and mental retardation presented himself with an increase in excretion of urinary orotic acid. Enzymatic studies revealed that the boy and his healthy mother were hereditary orotic aciduria heterozygote carriers. We can not prove that this pyrimidine disorder caused his neurological symptoms, but his pyrimidine nucleoside supply may have been insufficient in his neonatal period.

Cerebral Palsy↗
PubMed1998

Possible prediction of adverse reactions to fluorouracil by the measurement of urinary dihydrothymine and thymine.

Dihydropyrimidine dehydrogenase (DPD) deficiency with a defect of the pyrimidine catabolic pathway has recently become the focus of considerable attention, due to the severe 5-fluorouracil (5-FU) toxicities occurring in DPD deficiency patients. Studies also suggest that 5-FU toxicities could occur in another pyrimidine metabolic disorder, dihydropyrimidinuria (DHPuria). This study shows that urinary dihydrothymine (DHT) and thymine (THY) are useful indexes for detection of DPD deficiency and DHPuria. We measured urinary DHT and THY in 276 Japanese adults to establish reference ranges. When males and females were compared, both DHT and THY levels were found to be significantly higher in females. The reference ranges (mean +/- SD with logarithmic values) for males were found to be 1.56-5.70 micromol/g of creatinine for DHT and 0.40-1.47 micromol/g of creatinine for THY. The reference ranges for females were found to be 1.89-8.33 micromol/g of creatinine for DHT and 0.58-2.30 micromol/g of creatinine for THY. In addition to this study we analyzed a DPD deficiency case and a DHPuria case. In the DPD deficiency case, the THY concentrations of all urine samples were out of the reference range. However, uracil levels in most of the samples were within the normal range. The DHPuria case excreted large amounts of DHT and dihydrouracil, both out of the normal range.

Adolescent↗
PubMed1998

[A case of gastric cancer with decreased dihydropyrimidine dehydrogenase activity].

We analyzed the pyrimidine metabolite in the urine of a patient with severe mucositis and hand and foot syndrome, who was administered 5-fluorouracil for recurrence of gastric cancer. From our analysis, it was suggested that the patient had decreased dihydropyrimidine dehydrogenase activity. Dihydropyrimidine dehydrogenase activity is usually measured in peripheral blood mononuclear cells, but this time it was estimated from the analysis of uracil, dihydrouracil, thymine, and dihydrothymine in the urine. We concluded that urinary analysis of the pyrimidine metabolism is effective as screening for the prediction and prevention of 5-fluorouracil toxicity.

Adenocarcinoma↗
PubMed1998

Identification of novel mutations in the dihydropyrimidine dehydrogenase gene in a Japanese patient with 5-fluorouracil toxicity.

5-Fluorouracil (5-FU) is used widely in the treatment of several common neoplasms. Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-FU. Several recent studies have described a pharmacogenetic disorder in which cancer patients with decreased DPD activity develop life-threatening toxicity following exposure to 5-FU. We reported recently the first Japanese case of decreased DPD activity accompanied by severe 5-FU toxicity. The present study describes the results of molecular analysis of this patient and her family, in which three novel mutations (Arg21Gln, Val335Leu, and Glu386Ter) of the gene coding for DPD were identified. We also revealed that Arg21Gln and Glu386Ter are on the same allele and that Val335Leu is on the other allele, on the basis of analysis of the family genome. Expression analysis in Escherichia coli showed that Val335Leu and Glu386Ter led to mutant DPD protein with significant loss of enzymatic activity and no activity, respectively. The Arg21Gln mutation, however, resulted in no decrease in enzymatic activity compared with the wild type. The present data represent the first molecular genetic analysis of DPD deficiency accompanied by severe 5-FU toxicity in a Japanese patient.

Antimetabolites, Antineoplastic↗
PubMed1997

[The basics for establishing a needlestick injury prevention program in hospitals].

Although the risk of occupationally acquired infection is a matter of considerable concern for health care workers, the problem of needlestick injuries has yet to be fully understood in Japan. We investigated 257 cases of needlestick injuries in five Nagoya Municipal Hospitals from 1989 to 1994 using the Japan EPInet. The number of needlestick injuries increased each year of the study. In one of these hospitals, the Higashi Municipal Hospital, a specialist committee began activities in April, 1993, and protective equipment and devices were also introduced during 1994. HCV contamination injuries accounted for 70%-80% of the total number of injuries reported during the 1991-1994 period at the four hospitals and during 1991-1992 period at the Higashi Municipal Hospital. At the Higashi Municipal Hospital, HCV contamination injuries decreased from 22 cases (48%) in 1993, to 15 cases (25%) in 1994. The use of the Japanese EPINet for analytical purposes enabled us to clearly identify the causes and status of needlestick injuries, resulting in the establishment of an effective prevention program.

Female↗