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Biomedical subjects

C M White

Publications and source records attributed to C M White.

121 records · Page 7Linked to original sources

Organochlorine residues in Alaskan peregrines.

Organochlorine residue levels in eggs of Alaskan peregrines have remained essentially constant over the period 1969-73 despite decreased usage of these compounds in the United States and Canada. Studies on reproductive success in Great Britain and data on eggshell-thinning suggest that DDE residues above 20 ppm wet weight in peregrine eggs are associated with inability to maintain population levels. Residues in mainland Alaska are well above this critical figure and the reproductive rate is low. On the Colville River in northwestern Alaska, the last young falcons will fledge in 1975 and the remaining adult population will disappear by 1980 unless the present rate of reproductive failure is drastically and quickly reversed. In the Aleutians, however, levels range from 5 to 7 ppm and the reproductive rate is adequate to maintain the population.

Alaska↗

DDE residues and eggshell changes in Alaskan falcons and hawks.

Eggshell thickness after exposure to DDT was reduced by 21.7 percent in Alaskan tundra peregrines, by 16.8 percent in taiga peregrines, by 7.5 percent in Aleutian peregrines, by 3.3 percent in rough-legged hawks, and not at all in gyrfalcons. Tundra peregrine eggs contain an average of 889 parts of DDE per million (lipid basis); taiga peregrine eggs contain 673 parts per million; Aleutian peregrine eggs contain 167 parts per million; rough-legged hawk eggs contain 22.5 parts per million; and gyrfalcon eggs contain 3.88 parts per million. These changes in eggshell thickness and the pesticide residues reflect different degrees of exposure to contamination. There is a highly significant negative correlation between shell thickness and DDE content in peregrine eggs. Tundra and taiga peregrines have fledged progressively fewer young each year since 1966.

Alaska↗

Changes in P-wave dispersion and P-wave duration after open heart surgery are associated with the peak incidence of atrial fibrillation.

BACKGROUND: Increased P-wave dispersion (P-disp) and maximum P-wave duration (P-max) predict the development of atrial fibrillation (AF) in the general population. The present study evaluates the time-dependent relationship of P-disp and P-max after open heart surgery. METHODS AND RESULTS: P-disp and P-max were measured in the perioperative period of open heart surgery (one day before surgery through postoperative day 4). Compared with the baseline, P-max decreased immediately after open heart surgery (112.63 +/- 7.4 ms vs 106.9 +/- 8.2 ms, P =.005). An increase in P-disp was observed between postoperative days 1 and 2 (37.5 +/- 6.8 ms vs 43.1 +/- 4.5 ms, P <.05), and postoperative days 1 and 3 (37.5 +/- 6.8 ms vs 44.1 +/- 6.6 ms, P <.05). There was also an increase in the P-max between postoperative day 1 and 3 (103 +/- 8.3 ms vs 110 +/- 7.7 ms, P <.05). CONCLUSIONS: Nonuniform atrial conduction (P-disp) is greatest on days 2 and 3 after open heart surgery, and the longest atrial conduction time (P-max) is greatest on day 3 after open heart surgery, findings that coincide with the time of greatest risk for AF. (Heart Lung((R)) 2001;30:466-71.)

Aged↗

Characterization of the human hepatocellular carcinoma (hepg2) cell line as an in vitro model for cadmium toxicity studies.

Biochemical indicators and in vitro models, if they mimic in vivo responses, offer potentially sensitive tools for inclusion in toxicity assessment programs. The purpose of this study was to determine whether the HepG2 cell line would mimic known in vivo or in vitro (or both) responses of mammalian systems when confronted with cadmium (Cd2+). Uptake and compartmentalization of Cd2+, metallothionein (MT) compartmentalization, and glutathione (GSH) depletion were examined. In addition, several cytotoxic and stress effects, e.g., viability (neutral red [NR] uptake, 3-[4,5-dimethylthiozole-2-yl]-2,5,-biphenyl tetrazolium bromide [MTT] dye conversion, and live/dead [L/D]), membrane damage (lactate dehydrogenase leakage), metabolic activity (adenosine triphosphate levels), and detoxification capabilities (GSH content, cytochrome P4501A1/2 [EROD (ethoxyresorufin-o-deethylase)] activity, and MT induction), were measured in both naive (no previous exposure) and Cd2+ preexposed cells. Cadmium uptake increased during a 24-h period. Metallothionein induction occurred in response to both Cd2+ and ZnCl2; however, Cd2+ was the more potent inducer. Both Cd2+ and MT were localized primarily in the cytoplasmic compartment. All biochemical responses, except EROD, showed concentration- response relationships, after 24-h exposure to Cd2+ (ranges 0-3 ppm [26.7 microM]). Cadmium effects were reduced in preexposed cells, indicating adaptive tolerance or increased resistance had occurred. Twenty-four-hour LC50, dose causing death of 50% of the test subjects, values were 0.97, 0.69, and 0.80 ppm (8.7, 6.2, and 7.2 microM) for naive cells and 1.45, 1.21, and 1.39 ppm (12.9, 10.7, and 12.3 microM) for preexposed cells based on the NR, MTT, and L/D assays, respectively. These data indicate that this carcinoma cell line is a useful in vitro model for cadmium toxicity studies.

Biomarkers↗

Role of Clara cells and type II cells in the development of pulmonary tumors in rats and mice following exposure to a tobacco-specific nitrosamine.

The role of the Clara and type II cell in the development of pulmonary tumors in the A/J mouse and Fischer rat was investigated by determining the relationship of DNA methylation and repair in pulmonary cells to oncogene activation and by characterizing the morphology of pulmonary tumors induced by treatment with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Marked differences in the formation of the promutagenic adduct O6-methylguanine (O6MG) were observed in pulmonary cells following treatment of rats with NNK. Concentrations of this adduct in Clara cells greatly exceeded (3- to 30-fold) those detected in type II cells and whole lung with doses of NNK ranging from 0.1 to 50 mg/kg. In addition, very low rates of repair of this adduct were detected in Clara cells, whereas efficient adduct removal occurred in type II cells. The importance of this adduct and the role of cell specificity was suggested by the fact that a strong correlation was observed between the concentration of O6MG in Clara cells and tumor incidence in the Fischer rat with doses of NNK ranging from 0.03-50 mg/kg. In contrast, no differences in adduct concentration between type II and Clara cells from A/J mice were observed under conditions resulting in pulmonary tumor formation. Activation of the K-ras gene was detected in lung tumors from A/J mice. This gene was activated by a mutation in codon 12 involving a GC to AT transition (GGT to GAT) and is consistent with base mispairing produced by the formation of O6MG. Activation of this gene was not associated with lung tumor formation in the Fischer rat. DNA from rat lung tumors did induce tumors in the nude mouse carcinogenicity assay. In addition, rat repetitive sequences were detected in DNA isolated from these nude mouse tumors. In spite of the cell selectivity for DNA methylation in Clara cells from rat and the relationship between O6MG formation and tumorigenicity, early proliferative lesions observed in both mice and rats involved the alveolar areas. Ultrastructural examination of these lesions and adenomas revealed morphologic features characteristic of the type II cell. Thus the lack of agreement between biochemical and morphological findings makes it difficult to hypothesize a cell of origin for the pulmonary neoplasms induced by NNK. However, these studies indicate that the concentration of O6MG in Clara cells is an excellent indicator of the carcinogenic potency of NNK in the rat.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Sex, contraception and pregnancy among adolescents in foster care.

Young women aged 13-18 who were surveyed in a 1986 study of child welfare clients were over 50 percent more likely to have had sexual intercourse than those in a comparison group drawn from a national sample of young women; they were also more than twice as likely to ever have been pregnant. The child welfare teenagers also scored significantly lower than their counterparts on a test of sexuality and birth control knowledge. Among the child welfare clients (half of whom were at home and half of whom were in foster care), the young women living in foster homes were less likely than those living with their own families to have ever had sex voluntarily (33 percent vs. 47 percent). However, the foster children were less likely to have used birth control at their most recent intercourse or to have obtained contraceptives from a family planning clinic. Nearly half of the foster care teenagers and 40 percent of the teenagers living at home reported having been sexually abused. Victims of sexual abuse were especially likely to be sexually active. Among blacks, the teenagers in foster care and their national counterparts were similar in the proportions who had had sexual intercourse, who had had voluntary intercourse and who had ever been pregnant. Among whites, however, the foster care teenagers were about four times as likely as their matched peers to have had intercourse and to have had voluntary sex, and they were almost eight times as likely to have been pregnant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Sex education and family planning services for adolescents in foster care.

Representatives of public child-welfare agencies in 48 states were surveyed to determine their states' policies for meeting the sexual development and family planning needs of teenagers served by the agencies. Only nine states have a formal written policy dealing with this area of child welfare, and just two of the states have a comprehensive policy. A handful of states have deliberately avoided addressing the issue. Officials in other states believe that a formal policy would be counterproductive, arguing that a low-key approach is the best way to deal with the needs of the teenagers they serve. Finally, some state child-welfare officials admit that they have not given the issue much thought. Twenty-nine states offer foster parents special training in adolescent sexuality, and 19 offer such training to caseworkers; however, only five states mandate such training for foster parents and only four do so for caseworkers. Southern states are the most likely to have written policies, while western states are the least likely; western states also are the least likely to offer or mandate special training for caseworkers in contact with teenagers. The officials surveyed also identified a number of institutional barriers that prevent their agencies from developing and implementing policies to deal with the sexual development needs of children in state care.

Adolescent↗

Pharmacologic, pharmacokinetic, and therapeutic differences among ACE inhibitors.

Angiotensin-converting enzyme (ACE) inhibitors are a heterogeneous group of agents, and important pharmacologic, pharmacokinetic, and therapeutic differences among them must be understood to obtain optimal therapy. For patients with severe liver disease, lisinopril and captopril are not prodrugs (e.g., do not require hepatic activation), and lisinopril has almost solely renal elimination. Enalaprilat, the intravenous formulation of enalapril, is the only intravenously available ACE inhibitor and can be given to patients with severe liver dysfunction as it is also not a prodrug. Fosinopril is the only drug with compensatory dual routes of elimination, and it does not require dosage adjustment in patients with reduced renal function, as other ACE inhibitors do. Captopril and moexipril have potential drug-food interactions and are the only agents that should be spaced from meals. The ACE inhibitors also differ in their dialyzability, half-life, lipophilicity, trough:peak ratios, approved indications, and therapeutic information available for many indications.

Angiotensin-Converting Enzyme Inhibitors↗

The pharmacokinetics of intravenous estradiol--a preliminary study.

Estradiol USP was extemporaneously compounded for intravenous administration. Eight postmenopausal women were randomized to receive one of four estradiol dosages. Serum estradiol concentrations were determined at frequent intervals after single bolus dosing. The concentration-time profile was stripped and fit, and pharmacokinetic values were generated. Approximate dosage proportionality was seen with area under the curve, the terminal half-life was 27.45+/-5.65 minutes, and volume of distribution was very low (0.082+/-0.015 L/kg). Estradiol was well tolerated by all study participants.

Aged↗