Cross-training in 3-D.
With 3 hospitals and 10 perinatal nursing units, nurse leaders developed a cross-training program to unify staff for maximum flexibility, greater job satisfaction, and savings.
Clinical Competence↗
Biomedical subjects
J M Sanders
Publications and source records attributed to J M Sanders.
Disposition of 2-methylimidazole in rats.
2-Methylimidazole (2-MI), widely used as a chemical intermediate, is also present in cigarette smoke and may form in food and forage as a result of ammoniation of simple sugars. 2-MI has been shown to be neurotoxic in several animal species and to alter serum levels of T3, T4, and thyroid-stimulating hormone (TSH) in the rat, apparently leading to hyperplasia of thyroid follicular cells. In order to better characterize 2-MI-induced toxicity, the disposition of [2-(14)C]-2-MI has been investigated following p.o. administration of either 5, 50, or 150 mg/kg to male F344 rats. Excretion data indicated that absorption of 2-MI was both rapid and proportional to dose in the range studied. Approximately 90% of the total dose was eliminated in urine within 24 h. Most of the remaining 14C was excreted in feces and as expired 14CO2. Excretion data were similar following i.v. administration of 5 mg/kg. Little or no enterohepatic circulation of compound occurred, since biliary excretion of 2-MI-derived 14C was negligible. Approximately 70% of the 14C excreted in urine, following all dosing, consisted of parent compound. High-performance liquid chromatography (HPLC) chromatograms for all treatment groups were similar, indicating that metabolism of 2-MI in rats was not affected by dose or route of administration.
Administration, Oral↗
Determination of tamoxifen and metabolites in serum by capillary electrophoresis using a nonaqueous buffer system.
Tamoxifen (TAM), an antiestrogen, is widely used to treat hormone-dependent breast cancer in post-menopausal women. TAM may be used as a chemopreventive agent in women of child-bearing age; however, few data exist describing potential TAM-induced fetal toxicity. In support of the National Toxicology Program's characterization of reproductive and developmental effects of TAM, this work describes an analytical technique utilizing capillary electrophoresis (CE) for the detection of circulating levels of TAM, N-desmethyltamoxifen (DMT), and 4-hydroxytamoxifen (4-HT) in maternal rodent serum. Greater than 90% of 3H-labeled TAM was extractable from serum using 98:2 hexane-isoamyl alcohol. Optimum separation of TAM, DMT, and 4-HT was obtained on a 57 cmx50 microm capillary using a nonaqueous buffer system of 1:1 methanol-acetonitrile containing 50 mM ammonium acetate and 1% acetic acid. 4-Dimethylaminopyridine was used as internal standard. Temperature and voltage were optimized at 40 degrees C and 15 kV, respectively. The limit of detection of TAM by UV detection at 214 nm was approximately 800 amol. TAM and DMT were confirmed in serum of female rats 4 h following a single oral dose of 120 mg/kg. Transplacental exposure of TAM to fetal tissue will be evaluated using this technique.
Animals↗
Arterial thrombin activity after angioplasty in an atherosclerotic rabbit model: time course and effect of hirudin.
BACKGROUND: A 2-hour infusion of the direct thrombin inhibitor hirudin at the time of balloon angioplasty limits restenosis in the focally atherosclerotic rabbit. Although short-term administration of hirudin may have a prolonged biological effect, the effect of hirudin on vessel thrombin activity has not been previously studied in an animal model of angioplasty. We hypothesized that a short intravenous infusion of hirudin would result in prolonged inhibition of arterial wall-associated thrombin activity (ATA) after angioplasty. METHODS AND RESULTS: Sixty-one rabbits received recombinant hirudin (r-hirudin)(1 mg/kg bolus plus 1 mg x kg(-1) x h(-1)x2hours) or bolus heparin (controls, 150 U/kg) intravenously at the time of femoral balloon angioplasty. ATA was measured through exposure of arterial segments ex vivo to fibrinogen and conducting an assay for fibrinopeptide A (FPA). ATA was low in nonballooned, atherosclerotic vessels (FPA=0.5+/-0.3 ng x mL(-1) x mg(-1)) but increased significantly at 24 hours after angioplasty in the heparin group (3.7+/-0.9 ng x mL(-1) x mg(-1), P<.01 versus baseline, n=9) but not in the hirudin group (FPA = 1.4+/-0.3; P=NS versus baseline, P<.02 versus heparin controls, n=8). The time course of ATA after angioplasty was assessed in 44 rabbits. Thrombin activity peaked at 48 hours and declined to baseline at 72 hours and 7 days. FPA values between the heparin and r-hirudin groups were similar at these later time points. CONCLUSIONS: A 2-hour intravenous infusion of r-hirudin suppressed ATA measured 24 hours after angioplasty in the focally atherosclerotic rabbit. This prolonged biological effect may account, in part, for the reduction in restenosis seen in this model.
Angioplasty, Balloon↗
Comparative metabolism and disposition of ethoxyquin in rat and mouse. I. Disposition.
1. The biological fate of the antioxidant [3-14C]ethoxyquin (EQ) was investigated in the male F344 rat and the B6C3F1 mouse following either p.o. or i.v. administration. 2. The disposition of single doses up to 25 mg/kg was similar in the rat and mouse. About 90% of a total dose was excreted in urine and faeces within 24 h post-dosing. In contrast, no more than 60% of a higher dose of 250 mg/kg was excreted within 24 h following p.o. administration. 3. Metabolism of EQ was rapid in both the rat and mouse following either p.o. or i.v. administration. Little or no parent compound was detected in cumulative 24-h excreta. 5. EQ-derived radioactivity bioaccumulated in some tissues following repeated exposure to rat of either 25 or 250 mg/kg by gavage. However, the fold-increases in concentrations of EQ-derived radioactivity in tissues following repeated administration of the higher dose were generally less than those observed following repeated administration of the lower dose. Repeated high dose administration may overcome delayed gastric emptying (observed following single dose administration of 250 mg/kg) and/or lead to auto-induction of EQ metabolism.
Absorption↗
Comparative metabolism and disposition of ethoxyquin in rat and mouse. II. Metabolism.
1. The major pathways of ethoxyquin (EQ) metabolism in both the rat and mouse are O-deethylation and conjugation to endogenous substrates. 2. The two major EQ-derived metabolites excreted in rat urine were in the form of sulphate conjugates, 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline sulphate, and 1,2,3,4-tetrahydro-3,6-dihydroxy-4-methylene-2,2-dimethylquinoline sulphate. The latter apparently arises from an intramolecular rearrangement of the 3,4-epoxide of ethoxyquin. 3. Mouse urine contained one major glucuronide, 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline glucuronide as well as one major sulphate conjugate, 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline sulphate. 4. EQ-derived radioactivity was excreted in rat bile, mainly as GSH conjugates, with little unchanged EQ present. Two of the biliary metabolites are glutathione conjugates of ethoxyquin 3,4-epoxide; the third appears to be a conjugate of either ethoxyquin 7,8-epoxide or 2,2,4-trimethylquinol-6-one.
Animals↗
Toxicokinetics of the cholinomimetic compound benzyltrimethylammonium chloride in the male rat and mouse.
1. Benzyltrimethylammonium chloride (BTMAC)-derived radioactivity was rapidly eliminated from the F344 rat and the B6C3F1 mouse following p.o. administration of 0.63-63 mg/kg of [ring-U-14C] BTMAC. Greater than 90% of the radioactivity was excreted in urine and faeces within 24-h post-dosing. 2. BTMAC was poorly to moderately absorbed from the GI tract following p.o. administration. The percent of total dose absorbed did not exceed either 40% in the rat or 15% in the mouse. 3. Absorption was linear, but limited, over time following dermal administration of 63 mg/kg to the rat. Less than 10% of the total dose was absorbed from the skin within 24 h of BTMAC application. 4. Metabolism of BTMAC was minimal in both the rat and mouse. Toxicity (excessive cholinergic stimulation and mortality) appears to be attributable to the parent compound. 5. The limited absorption and rapid elimination of BTMAC should result in little or no bioaccumulation in tissues following repeated exposure to low levels of this compound. The results suggest that greater human health risks may be associated with acute high level exposure rather than chronic low level exposure.
Absorption↗
Implantable intravenous access devices in children with hemophilia.
Explore the source record for details and available documents.
Adolescent↗
Pediatricians' views of access to health services for adolescents.
PURPOSE: The American Academy of Pediatrics (AAP) carried out a member survey to measure pediatricians' views of parental permission and notification for selected health services for two age groups of adolescents, the 13 to 15 year olds and the 16 to 17 year olds. METHODS: Through an AAP Periodic Survey, a sample of 1000 members of the AAP were sent questionnaires to fill out and return. The response rate was 77%. RESULTS: The majority of pediatricians in all groups examined believed parental permission and notification were important for general medical and surgical care. But for most other types of care delineated, related to substance abuse and sexuality, most pediatricians did not believe parental permission should be required, except for requests for abortion for 13-15 year olds. For several types of care most pediatricians believed parental notification should be required for 13-15 year olds. Older pediatricians, male pediatricians, and self-employed pediatricians were more apt to support both parental permission and notification for all types of care. When age, gender and self versus not self-employed were introduced together through a logistic regression procedure differences in views were accounted for by self versus not self-employed, and age and gender had no additional impact. CONCLUSIONS: Most pediatricians supported the right of minors to seek care without parental permission for care related to substance abuse and sexuality. The majority were less likely to grant confidentiality to adolescents, particularly those 13 to 15 years.
Adolescent↗
Genes involved in production of plasmidlike forms by a Bacteroides conjugal chromosomal element share amino acid homology with two-component regulatory systems.
Many human colonic Bacteroides strains carry large (greater than 70-kbp) self-transmissible chromosomal tetracycline resistance (Tcr) elements. These Tcr elements can also mediate the excision and circularization of discrete nonadjacent segments of chromosomal DNA which are designated NBUs (nonreplicating Bacteroides units). We have localized a 6.5-kbp segment of Tcr element DNA that mediates NBU excision and circularization. Analysis of the DNA sequence of this region indicated that it contained three open reading frames, all transcribed in the same direction. The first gene was the Tcr gene, tetQ. The second two open reading frames exhibited amino acid similarity to known two-component regulatory systems. Complementation and gene fusion data supported the hypothesis that the three genes were organized in an operon. Transcription from the tetQ promoter region was inducible by tetracycline, as might be expected from the previous finding that NBU excision was detectable only in cells preexposed to tetracycline. The 6.5-kbp region appeared to be essential not only for NBU excision but also for self-transfer of the elements, another activity that is enhanced by preexposure to tetracycline. Accordingly, the two genes downstream of tetQ have been designated rteA and rteB (regulation of Tcr elements).
Amino Acid Sequence↗
Secondary myelodysplastic syndrome complicating therapy for osteogenic sarcoma.
A 12-year-old girl with nonmetastatic osteogenic sarcoma received treatment with doxorubicin, methotrexate, cisplatin, cyclophosphamide, bleomycin, and dactinomycin. She developed unexplained persistent pancytopenia after completion of chemotherapy. Twenty-three months after the initial diagnosis of osteosarcoma an evaluation revealed a bone marrow pattern consistent with the diagnosis of refractory anemia with excess blasts, and karyotype analysis showed characteristic findings of therapy-related myelodysplasia (loss of chromosomes 5 and 7, as well as 12p and 17p deletions). Bone marrow transplantation from an human leukocyte antigen (HLA)-compatible sibling donor was performed 26 months after the diagnosis of the primary malignancy. Although it is unproven that the alkylating agents administered to this patient were responsible for the myelodysplastic syndrome, careful follow-up of osteosarcoma patients who receive alkylating agents is warranted.
Antineoplastic Combined Chemotherapy Protocols↗
Malignant rhabdoid tumor: a highly malignant childhood tumor with minimal karyotypic changes.
Malignant rhabdoid tumors (MRT) are rare; thus very few cytogenetic studies of this type of tumor have been performed. We report the results of cytogenetic studies of 10 MRTs from various anatomic primary sites. Six cases had normal diploid karyotypes with no detectable rearrangements or aneuploidy except for occasional tetraploid cells. In 4 of these cases the tumor phenotype was verified by electron microscopic studies. In a seventh case only normal cells were identified in short-term culture, but a del(13)(q14) appeared after 4 months in culture. A soft tissue MRT contained a translocation, t(8;15)(q12;p11), and a liver MRT contained a del(3)(q21) or t(3;?)(q21;?). The single case of a primary brain MRT had monosomy 22 with deletion of part of the remaining chromosome 22. Our findings indicate that visible chromosomal rearrangements occur in fewer than half of MRTs. When combined with other reported series, our study indicates that monosomy 22 is a non-random chromosomal abnormality in primary MRT of the brain.
Brain Neoplasms↗
Diagnosis of adolescent hypertension on initial screening by the use of height age.
The tremendous variability in growth and maturation during adolescence makes body mass a better determinant of blood pressure (BP) than chronologic age (CA). To evaluate whether two accepted indicators of body mass, height age (HA), and weight age (WA) could accurately predict hypertension on initial screening, 1426 healthy adolescents had their BP, height, and weight measured and Tanner stage assessed. The mean of three BP measurements were compared to eight published nomograms which correlate BP with height, weight, or CA. Patients with an initial elevated BP (greater than 95 percentile for height, weight or CA) were reevaluated to verify persistent hypertension. Eighty-seven (6.1%) initially appeared to be hypertensive with 0.84% persistently hypertensive. The diagnosis of hypertension varied considerably when the BP measurements were reevaluated based on HA or WA. Height age was the most sensitive (100%) and specific (62.6%) criteria for the diagnosis of hypertension and can be used for initial BP screening in this age group.
Adolescent↗
The bleeding time may be longer in children than in adults.
The bleeding time, the most frequently performed test reflecting in vivo platelet function, is the duration of blood flow from a standardized incision on the volar surface of the forearm. Normal values have been determined in adult subjects, but with the exception of neonates, data on the range of bleeding time values in pediatric patients are unavailable. Standard hematology textbooks imply that bleeding time values in children are similar to those of adults. We have reviewed our 9 years of experience with 137 children (mean age 6.5 years) who were referred for diagnostic evaluation of a bleeding disorder but whose history and physical examination were felt by us to be inconsistent with an abnormality of hemostasis. Bleeding time values in these individuals (mean 6.0 min, 95th percentile 9.0 min) were compared with those of 85 normal adult volunteers (mean 4.4 min, 95th percentile 6.5 min). The Simplate-I disposable device and vertical (perpendicular to elbow crease) incision direction were used in both groups. This difference between the pediatric and adult bleeding time values is statistically significant (p less than 0.0001). Neither age nor sex had a significant effect on the pediatric bleeding time measurements. We conclude that the bleeding time, when performed as described, is longer in children than in adults and that pediatric standards for bleeding time should be used in order to avoid a spurious diagnosis of a primary hemostatic disorder in some normal children.
Adolescent↗
Vaginal absorption of polyvinyl alcohol in Fischer 344 rats.
Polyvinyl alcohol (PVA) is a polymer with a wide range of molecular weights and uses. Recently, low molecular weight formulations of PVA have been used as components of contraceptive products designed for intravaginal administration in human females. Previous studies in animals have determined that little or no absorption of PVA occurs from the gastrointestinal (GI) tract. However, there is some concern that PVA of lower molecular weights might be absorbed across membranes of the reproductive tract. Consequently, this work has investigated the absorption of low molecular weight PVA across biological membranes of the reproductive and GI tracts of Fischer 344 rats. Oral administration of ten consecutive daily doses of 14C PVA resulted in little apparent absorption of the dose from the GI tract. In contrast, intravaginal administration of 14C PVA resulted in increasing concentrations of PVA-derived radioactivity in major tissues following one, three or ten daily doses of the estimated human dose of 3 mg/kg. PVA-derived radioactivity was concentrated mainly in the liver, reaching a peak greater than 1750 ng equivalents/g tissue 24 hours following ten daily doses. Over 300 ng equivalents/g tissue were still present in the liver 30 days following the last dose.
Absorption↗
Effects of dose, age, inhibition of metabolism and elimination on the toxicokinetics of 2-butoxyethanol and its metabolites.
Acute exposure to 2-butoxyethanol (BE) causes dose- and age-dependent hemolytic anemia in rats. Recently, we have shown that butoxyacetic acid (BAA) is the proximate hemolytic agent and that inhibition of alcohol or aldehyde dehydrogenases protected rats against BE-induced hemolytic anemia. In the present investigations, the kinetics of 14C-BE metabolism and clearance were studied in control adult (3-4 months old) and old (12-13 months old) male F344 rats and in adult male F344 rats treated with pyrazole, cyanamide or probenecid. Our results showed that the area under the curve (AUC), maximum plasma concentration (Cmax) and systemic clearance (Cls) of BE were dose-dependent. In contrast, there was no effect of dose on half-life (T1/2) or volume of distribution (Vd) of BE. These results also showed that there was no age effect on T1/2, Vd or Cls of BE. However, Cmax and AUC of BE increased as a function of age. Also, analysis of variance indicated no significant interactions (P less than or equal to .05) between dose and age in relation to BE kinetics. As expected, inhibition of BE metabolism by pretreatment of rats with pyrazole or cyanamide resulted in a significant increase in the T1/2 and AUC of BE, whereas it caused a significant decrease in the Cls. Furthermore, pyrazole had no effect, whereas cyanamide had decreased Vd of BE. Analysis of the toxicokinetic parameters of BAA revealed that T1/2, AUC and Cmax of BAA were directly related to the age of the rats and the dose of BE administered.(ABSTRACT TRUNCATED AT 250 WORDS)
Age Factors↗
Comparative metabolism and disposition of ethyl carbamate (urethane) in male Fischer 344 rats and male B6C3F1 mice.
The metabolism, disposition, and excretion of ethyl carbamate (EC) was investigated following oral or iv administration of a wide range of doses to male rats and mice. At a low dose, 4.75 mg/kg, administered iv, approximately 98% was exhaled as CO2 within 8 or 12 hr by mice or rats, respectively. However, as the dose increased, the percentage of dose eliminated as CO2 decreased in a dose-dependent manner which was much more pronounced in rats than mice. At all doses studied, mice eliminated EC as CO2 (as % dose) more rapidly than rats. Evidence of saturation of metabolism and elimination was observed at doses greater than 4.75 mg/kg in rats and greater than 47.5 mg/kg in mice. Following iv administration of 47.5 or 475 mg/kg, EC was initially evenly distributed in all tissues of each species except fat. After the initial time point (15 min), rat tissues contained higher concentrations of 14C compared to tissues of mice receiving the same dose. The disappearance of 14C from blood and various tissues followed monoexponential kinetics with rates dependent upon the species and the dose but independent of the tissue. Following oral administration, EC was completely absorbed from the gastrointestinal tracts of rats and mice at all doses studied. Approximately 5, 0.7, and 1% of the doses were excreted in urine, in feces, and as volatile organics, respectively. EC was neither an inducer nor an inhibitor of its own metabolism to CO2 following daily treatment of rats with oral doses of 47.5 mg/kg for 9 days. Only the parent compound was present in blood, lungs, skin, liver, kidney, muscle, and bile of treated rats. The urinary metabolic profile of EC was not affected by the route of administration in either species; however, in the rat but not in the mouse it was influenced by dose. Pretreatment of rats with piperonyl butoxide or SKF 525A (cytochrome P-450 inhibitors) or tri-o-cresyl phosphate (TOCP) or paraoxon (carboxylesterase inhibitors) or methyl carbamate (competitive substrate) did not greatly alter the metabolism of EC to CO2. The in vitro metabolism of EC to CO2 was not highly localized in any particular tissue or subcellular fraction of liver and was not affected by NADPH, GSH, NADH, or combinations of these cofactors. This work indicates that a number of studies of EC carcinogenicity have used doses that exceed the capacity of rats and mice to metabolize this chemical in a linear fashion.
Animals↗
Sexual behavior and contraceptive risk taking among sexually active adolescent females.
Drawing on DeLamater's conceptual model of premarital contraceptive activity, this study assessed the relationships between various social, developmental, and behavioral variables and contraceptive risk taking by sexually active adolescent females. The hypotheses were tested on a national random sample of unmarried sexually active adolescent females (n = 1512) ages 15-20 years from Cycle III of the National Survey of Family Growth. The number of years the subjects had been sexually active was the strongest predictor of their frequency of sexual intercourse, followed by their frequency of attendance at religious services. The inverse relationship between religious attendance and coital frequency was much stronger among whites than blacks. When the influence of these variables on contraceptive risk taking was assessed, coital frequency explained 7.2% of the variation in contraceptive risk taking, with the number of years the adolescent had been dating explaining a small amount of additional variation. Our data support not only the first stage of DeLamater's conceptual model of premarital contraceptive activity, but also aspects of Jessor's more general theory of adolescent risk taking and problem behavior.
Adolescent↗