ABSTRACT. Random urine samples were obtained from 31 patients with neuroblastoma (newborn to 8 yr of age) and from PO0 children without this tumor (newborn to 10 yr). The urine samples were studied for the presence of sulfate and glucuronide conjugates of homovanillic (HVA), dihydroxyphenylacetic, vanilmandelic, and vanillactic acids. The urinary concentrations of these acids were determined by capillary gas-chromatography before and after enzymatic treatment with glucuronidase and sulfatase. Concentrations of the "free" fraction and "total" urinary content of these acids were determined using the results from untreated and treated urines respectively. Age-related reference values were established for children without neuroblastoma. Fractions of the total content of urinary HVA (18-39%) and dihydroxyphenylacetic acid (36-66%) were excreted as glucuronides and/or sulfates by the control group, with the highest conjugated fractions found in the urine of young infants (0-3 months). Vanilmandelic was excreted mainly as "free" acid (unconjugated), whereas vanillactic acid was undetectable in almost all control samples. Patients with neuroblastoma also excreted a fraction of these acids as glucuronide and/or sulfate conjugates, (25% of urinary HVA, 39% of dihydroxyphenylacetic acid and 45% of vanillactic acid) whereas vanilmandelic acid was excreted only as "free" in controls. Determination of "total" rather than "free" urinary HVA was diagnostic in one neuroblastoma patient with borderline "free" HVA levels, whereas determination of "free" or "total" dihydroxyphenylacetic acid and vanillactic acid did not improve the diagnostic sensitivity in the cases examined. We conclude that it may be clinically useful to determine "total" urinary HVA in patients with borderline "free" HVA levels who are suspected of having neuroblastoma. (Pediatr Res 23: 576-579,1988) Abbreviations HVA, homovanillic acid DOPAC, 3,4-dihydroxyphenylacetic acid VMA, vanilmandelic acid VLA, vanillactic acid UCr, urinary creatinine concentration Most children with neuroblastoma excrete higher than normal amounts of catecholamine metabolites in their urine (1-3). The measurement of urinary catecholamine metabolites has been used routinely to establish or confirm the diagnosis of this tumor (4, 5). Three main groups of catecholamine metabolites have been found in elevated concentrations in the urines of neuroblastoma patients I) acidic derivatives including HVA, VMA, DOPAC, and VLA; 2) Alcoholic derivatives including: 4-hydroxy-3-methoxyphenylethylglycol (HMPG) 3,4 dihydroxyphenylethylglycol; and 3) metanephrines. Of the metabolites listed above, HVA and VMA are used most often as neuroblastoma markers because they are excreted most consistently in elevated amounts by patients with neuroblastoma (5). Of patients with neuroblastoma 92% have elevated concentrations of HVA and/ or VMA in random urine samples at diagnosis (6). The use of prolonged urine collections rather than random urine samples is not advantageous in respect of diagnostic sensitivit...
It is havn that mug dependent wan?n ( m ) have an increased incidence of medical and obstetrical conplications, but little infomation exists on the intrvtm cmse and managanent of these patients. Within the context of Family Center, a clinical and research W g r m pmviding cqmhensive pand postnatal services for CDW and their infants, a study was undertaken to determine if the DtM had n o d patterns of labor and if standard intraprtm managanent is appopriate. The study population included 336 wwen who delivered between January 1982 and July 1984, of which 112 were CIW (72% receiving methe done maintenance). The canparison group of 224 non-drug dependent wan?n was matched for gravity, parity and socioeconcmic background. The incidence of wmature delivery, abruptio placentae, breech wsentation and intrauterine grmth retardation were significantly greater in the m. The average duration of the first, second and third stages of labor canpared well with the n o d course of labor and matched the results of the canparison group. Labor abnormalities and cesarean sections were of no greater incidence, but there were more than twice as mmy forceps deliveries which coincides with the 40% increased use of epimal anesthesia. Analgesia and anesthesia were in excess of that which is given to the average patient. There were three stillborns, one neonatal death, and one maternal death. Apgar scores and the incidence of fetal distress and meconim staining were identical in both groups. Postptm canplications were more cormon in the DtM, but most were secondary to the use of subclavian intravenous lines inserted due to the presence of sclerotic veins. These data suggest that high risk prenatal managanent and ca~eful monitoring in the intraand postpartm periods utilizing epidural anesthesia identifies and usually wvents untmuard cmplications in m . Acetaminophen (A4AP) is known to be activated by oxidative metabolism to a reactive iminoquinone. Two structural analogues, N-Acetyl-3-AminoPhenol (A3AP) and N-Acetyl-2-AminoPhenol (AZAP) have been studied as to their oxidation. A2AP is more reactive than A4AP whereas A3AP is not oxidizable to an iminoquinone using an electrochemical cell. Using the in vitro human lymphocyte/ mouse hepatic microsome method which demonstrated toxicity of A4AP we have shown that A2AP is a more potent cytotoxic agent than A4AP and that A3AP is devoid of toxicity (Table). This is consistent with the observation that A3AP is not hepatotoxic in animals but contradicts the observation that AZAP was also not hepatotoxic. Previous arguments as to the necessity for Nhydroxylation to activate A4AP to a reactive species are not substantiated by these observations. AZAP, not hydroxylated due to steric constraints, is readily oxidized and is very cytotoxic. Its apparent lack of toxicity in animals was likely an artifact of its rapid clearance in vivo. A3AP, the non-toxic analogue & The role of phenytoin(DPH) in causing birth defects is uncertain. Only a minority of fetuses exposed to DPH have malformations. Arene oxide me...
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