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Biomedical subjects

J N Miceli

Publications and source records attributed to J N Miceli.

At least 19 recordsLinked to original sources
PubMed1988

Pharmacokinetics of propylthiouracil in children and adolescents with Graves' disease in the hyperthyroid and euthyroid states.

The pharmacokinetics of propylthiouracil (PTU) was studied in 7 patients having Graves' disease when they were hyperthyroid and then again when they were euthyroid. Two additional euthyroid patients were also studied. The t1/2, Ke, Ka, apparent Vd, AUC and clearance were calculated. Serum T3 and T4 were also measured. PTU had an immediate effect in reducing T3 levels. Although there were intraindividual variations, the mean PTU elimination half-time did not change from the hyperthyroid state (1.47 h) to the euthyroid state (1.53 h). The mean Ka when hyperthyroid (2.12 h-1) was significantly increased (p less than 0.005) compared to when euthyroid (1.00 h-1). The calculated kinetic information indicates that the disposition of PTU in children is similar to that reported in adults.

Adolescent↗
PubMed1987

Chloramphenicol and vancomycin.

These two antibiotics have been important agents in the treatment of serious infections. Chloramphenicol use is decreasing owing to the potentially fatal toxicities associated with its use. Vancomycin use, on the other hand, is increasing owing to the emergence of methicillin-resistant staphylococci. It is important to routinely monitor serum concentrations of these drugs. An overview of the pharmacology and methods of analysis for each drug is presented in this review.

Chloramphenicol↗
PubMed1985

Persistence of polybrominated biphenyls (PBB) in human post-mortem tissue.

Polybrominated biphenyl (PBB), a fire retardant, was accidentally substituted for an animal feed supplement in Michigan 10 years ago. This led to widespread livestock contamination and ultimately to contamination of virtually every human residing in the State at that time. In order to evaluate the extent of PBB persistence and distribution in human tissues 10 years after this accidental poisoning, a study was conducted on a series of autopsy cases from the Grand Rapids ("high" exposure) area of the State. No attempt was made to relate cause of death to PBB exposure or tissue concentration. Samples of 196 tissues from 15 subjects were analyzed for PBB content, and levels were determined by measurement of the hexabromobiphenyl peak using electron capture gas chromatography. Only 4 of the 196 samples analyzed did not have PBB concentration above the limit of detection (0.5 ng/g). As expected, fat and fat-rich tissue had the highest PBB concentration. Perirenal fat had the highest mean concentration (475 ng/g). Adrenal, atheromatus aorta and thymus had mean concentrations about half that of perirenal fat; all other tissues had mean concentrations one-tenth or less of perirenal fat. The results document that PBB is still present in human tissue and that PBB was distributed in all tissues examined. The PBB fat elimination half-time was estimated to be at least 7.8 years. If this is approximately correct, PBB will persist in tissues throughout the lifetime of humans so contaminated.

Adipose Tissue↗
PubMed1984

Metabolism and pharmacokinetics of acetaminophen in a severely poisoned young child.

A 1-year-old child with severe acetaminophen (APAP) poisoning after ingestion of 10 gm APAP demonstrated central nervous system depression, shock, hypothermia, and metabolic acidosis. There was dramatic improvement during treatment with intravenously administered N-acetylcysteine (NAC) and hemodialysis, and the patient recovered without sequelae. A detailed study of APAP metabolism was carried out during the initial 72 hours after ingestion. APAP-sulfate and APAP-glucuronide accounted for 29% and 33%, respectively, of total drug in urine, whereas cysteine and NAC conjugates accounted for only 12%. The low incidence of severe toxicity in children after overdoses of APAP may be related to greater capacity to metabolize APAP via a nontoxic pathway.

Acetaminophen↗
PubMed1984

Analysis of caffeine: comparison of the manual enzyme multiplied immunoassay (EMIT), automated EMIT, and high-performance liquid chromatography procedures.

Caffeine has been recommended for the treatment of apnea in newborn children. Most of the current methods for measurement of caffeine in newborns have used high-performance liquid chromatography (HPLC) because analysis can be performed on as little as 50 microliter of serum, an important factor when obtaining multiple blood samples for routine drug monitoring in infants and children. We evaluated the manual Syva enzyme multiplied immunoassay technique (EMIT) caffeine procedure and compared the assay results with our HPLC caffeine method. The EMIT procedure was also automated, and these results were compared with those of the manual and HPLC procedures. The 7-micrograms/ml calibrator was analyzed 20 times to establish within-run precision for the manual procedure. The mean +/- SD was 6.97 +/- 0.33, and the coefficient of variation (CV) was 4.80%. Reproducibility was tested by multiple analysis of the 11-micrograms/ml control. The mean +/- SD (CV) for the manual system was 11.3 +/- 0.45 (4%), n = 17; for the HPLC system, 10.58 +/- 0.89 (8.4%), n = 10; and for the automated system, 10.4 +/- 0.78 (7.5%), n = 12. Samples from 32 patients were analyzed by each of the above procedures. There was a good correlation among all three procedures. The correlation coefficient (r) for HPLC vs. manual EMIT was 0.98; for HPLC vs. automated EMIT, 0.97; and for automated EMIT vs. manual EMIT, 0.96. We conclude that the new Syva EMIT caffeine method is reliable and reproducible and can be applied to automated analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Caffeine↗
PubMed1981

Tissue distribution and elimination kinetics of polybrominated biphenyls (PBB) from rat tissue.

The concentration of polybrominated biphenyl (PBB) in serum in a large number of organs was determined in a population of rats for 36 weeks a single dose of PBB. Groups were killed at 6, 12, 24 and 36 weeks after exposure to PBB (1 mg/100g body wt, i.p.). Growth, weight gain and appearance of the rats and their internal organs were normal. Complex and varied relationships were found in tissue concentrations with time after PBB administration. Serum and fat had apparent first-order elimination kinetics with calculated half-times of 23.1 and 69.3 weeks, respectively. For five other tissues, apparent t 1/2s ranged from 9.0-63 weeks, while for four others, kinetics could not be determined from these 4 time points. It is likely that a substantial residue of PBB will still remain in the body of the rat at the end of its life span because of the persistence of PBB in lipid-rich tissues (adipose, adrenal, and brain).

Adipose Tissue↗
PubMed1981

Pharmacokinetics of chloramphenicol and chloramphenicol succinate in infants and children.

The metabolism and elimination of chloramphenicol-3-monosuccinate was studied in 45 infants and children, ages 3 days to 16 years, during intravenous administration. The apparent half-life of chloramphenicol was extremely variable, ranging from 1.7 to 12.0 hours with a mean of 5.1 hours. Apparent half-lives were inversely correlated with age. Chloramphenicol-S serum concentration declined biexponentially in most patients, with an estimated mean initial half-life of 0.7 hours and a subsequent longer mean half-life of 2.2 hours. Chloramphenicol-S persisted in serum up to six hours after a dose, and comprised a significantly larger fraction of total chloramphenicol in the serum of infants under one month of age than in older infants and children. A widely variable fraction of the administered chloramphenicol-S dose, with a mean of 33%, was excreted in the urine unchanged and was, therefore, not bioavailable in active form. Mean renal clearance of chloramphenicol-S was 259.5 ml/minute/1.73 M2, four times the mean creatinine clearance, indicating active tubular secretion. Variable hydrolysis and renal elimination of nonhydrolyzed chloramphenicol-S reduces the bioavailability of the antibiotic and appears to contribute substantially to the wide variation in apparent half-life and poor correlation between dose and serum concentration of free chloramphenicol.

Adolescent↗
PubMed1981

Elimination kinetics of isoniazid in the newborn infant.

The elimination of isoniazid was followed in 2 newborn infants who had received the drug transplacentally, and in 1 of the mothers. The half-time for serum elimination for mother No. 1, babies No. 1 and 2 were calculated as 3.0, 7.8 and 19.8 h, respectively. Near equality existed between maternal and newborn serum isoniazid concentrations. Additional studies are required to determine the acetylation capacity of newborns.

Female↗