Computerized tomography (CT)-guided stereotactic biopsies of intracranial lesions in 29 patients were analyzed, paying particular attention to the correlation between core biopsies and aspiration smears. Seven percent were nondiagnostic due to sampling error. Discrepancies occurred between core biopsies and aspiration smears in 10% of the cases. In two instances of such discrepancies, cytologic findings on the aspiration smear yielded the diagnosis of metastatic tumor. One patient, with herpetic encephalitis, was diagnosed by electron microscopic review of the core biopsy only. One patient died of an intraoperative hemorrhage, a complication of the fine-needle technique.

Biopsy↗

PubMedDate not supplied

Structure-activity relationships in allergic contact dermatitis.

Skin sensitization by simple chemicals involves reaction with nucleophilic groups on skin proteins or possibly on proteins in cell membranes to form haptenic groups, which act as allergenic determinants. A quantitative model for sensitization by 'alkylating agents', the RAI (Relative Alkylation Index) theory, has been devised and applied to the sensitization observed with three model series of compounds--p-nitrobenzyl halides and saturated and unsaturated sultones. Examination of chemical structures, and predictions of the types of chemical reaction that substances may undergo, can be used to assess the likely reactivity of unknown materials towards skin proteins. In addition such examinations of structure may be used to assess the likely cross-reactivity of materials. The pro-hapten concept of Dupuis & Benezra (Allergic Contact Dermatitis to Simple Chemicals. A Molecular Approach. Marcel Dekker, New York) offers an explanation for the sensitization potential of substances that do not contain chemically reactive groups prior to in vivo conversion and for cross-reactions between apparently unrelated chemicals.

Alkylation↗

PubMedDate not supplied

Dioxin incinerator emissions exposure study Times Beach, Missouri.

PURPOSE: To determine whether living in the vicinity of a hazardous waste incinerator that was burning material contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increased TCDD and toxicity equivalencies (TEQ) in individuals living near the incinerator. METHODS: Participants were randomly chosen from an area close to the incinerator and compared to participants outside of the exposure area. TCDD and related compounds were measured in blood serum before incineration, four months after incineration started, and at the end of incineration. RESULTS: Lipid adjusted serum levels of TCDD and TEQ decreased from pre-incineration to four months after incineration, and decreased further by the end of incineration. CONCLUSION: Incineration of TCDD did not result in any measurable exposure to the population surrounding the incinerator.

Adolescent↗

PubMedDate not supplied

The reliability of 2,3,7,8-tetrachlorodibenzo-p-dioxin and toxicity equivalence measurements in Missouri residents.

This study evaluates the reliability of serum measurements of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and toxicity equivalence (TEQ) in individuals with no prior exposure to TCDD or dioxin-like compounds above background levels. Reliability was measured over three time-periods in the same individuals. TCDD and TEQ were measured in 127 and 128 participants. The values declined during the testing periods. Reliability coefficients for TCDD was 0.69 and for TEQ 0.91 but increased to 0.79 and 0.92, respectively, after removal of three outlying cases. Study results show good reliability over 22 months suggesting a consistency in the uptake and excretion of TCDD and other dioxin-like compounds.

Adult↗

PubMedDate not supplied

Structure-activity relationships for contact allergenic potential of gamma,gamma-dimethyl-gamma-butyrolactone derivatives. 1. Synthesis and electrophilic reactivity studies of alpha-(omega-substituted-alkyl)-gamma,gamma-dimethyl-gamma-butyrolacton es and correlation of skin sensitization potential and cross-sensitization patterns with structure.

A series of alpha-(X-substituted-methyl)-gamma,gamma-dimethyl-gamma-butyrolactones (series 1), a series of alpha-(2-X-substituted-ethyl)-gamma,gamma-dimethyl-gamma-butyrolactones (series 2), where X is a leaving group, and the compound alpha-(3-bromopropyl)-gamma,gamma-butyrolactone (3) were synthesized. Their reactions as electrophiles toward n-butylamine, used as a model for nucleophilic groups on skin proteins whose in vivo chemical modification leads to skin sensitization, were investigated. The compounds of series 1 were shown to react via a two-stage elimination--Michael addition sequence whereby the elements of HX are eliminated to form alpha-methylene-gamma,gamma-dimethyl-gamma-butyrolactone, which reacts more slowly with n-butylamine to give alpha-[(N-butylamino)methyl]-gamma,gamma-dimethyl-gamma-butyrolactone. The compounds of series 2 and compound 3 were shown to react with n-butylamine via a single-stage substitution reaction to give respectively alpha-[2-(N-butylamino)ethyl]- and alpha-[3-(N-butylamino)propyl]-gamma,gamma-dimethyl-gamma-butyrolactones . Rate constants for these reactions have been determined, and it is found that substitution reactions of series 2 and compound 3 are slower than Michael addition of alpha-methylene-gamma,gamma-dimethyl-gamma-butyrolactone, which in turn is slower than the elimination reactions of series 1. The results of guinea pig skin sensitization tests on these compounds were found to be consistent with the above findings in that the compounds of series 1 were found to be in general much stronger sensitizers than those of series 2 and compound 3. The results of cross-challenge tests indicate that sensitizing compounds from series 2 were cross-reactive with both series 1 and compound 3 but that compound 3 is only weakly cross-reactive with series 1. These observations indicated that for these compounds a difference of two carbon atoms between the determinant groups transferred to protein had a markedly greater effect than a difference of one carbon atom on antigenic specificity.

4-Butyrolactone↗

PubMedDate not supplied

Structure-activity relationships for contact allergenic potential of gamma,gamma-dimethyl-gamma-butyrolactone derivatives. 2. Quantitative structure-skin sensitization relationships for alpha-substituted-alpha-methyl-gamma,gamma-dimethyl-gamma-butyrolactone s.

A skin sensitization cross-challenge dataset for a series of alpha-(X-substituted-methyl)-gamma,gamma-dimethyl-gamma-butyrolactones is analyzed in terms of the relative alkylation index (RAI) model. The data analyzed consist of guinea pig sensitization response data for tests in which one lactone derivative is used for the induction stage and then the animals are challenged with another lactone derivative to elicit the response. RAI values are based on calculated log P (octanol/water) values together with measured relative rate constants for reactions of the lactones with n-butylamine to form alpha-methylene-gamma,gamma-dimethyl-gamma-butyrolactone. Plots of biological response against RAI for induction (RAIi) for sets of data in which the same compound is used for challenge have the double-sigmoid shape typical of sensitization response--RAIi plots, with some points in the overload region. Relative elicitation potential (REP) values, defined in terms of the biological response when sensitized animals are challenged with the compound in question relative to the response when the same animals are challenged with a chosen reference compound, are obtained. Consistent with the RAI model, plots of REP against RAIc, the RAI value corresponding to challenge, are linear and the slopes of plots corresponding to different reference compounds are, within the limits of experimental error, in the same ratio as the REP values of the reference compounds. Finally, multiple linear regression analysis gives a quantitative structure-activity relationship (QSAR) covering the complete set of cross-challenge data, relating the biological responses to the RAIi and RAIc values.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗

PubMedDate not supplied

A medical follow-up of the health effects of long-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The human health effects of long-term exposure to low levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have not been well established. The results of a prior study showed that persons exposed to TCDD had depressed cell-mediated immunity, and 18 of 51 persons had anergy or relative anergy on skin testing. This paper presents the results of a medical follow-up on participants who were reported to be anergic or relatively anergic in the earlier study. None of the participants in the follow-up study was anergic, and only one exposed and one unexposed participant were relatively anergic. Several technical and biological possibilities for the difference in results of the two studies are presented. The possibility that recovery from the effects of TCDD exposure caused the differing results is the least plausible explanation for the changes in the skin test results.

Adult↗

PubMedDate not supplied

Prenatal determination of obesity, tumor susceptibility, and coat color pattern in viable yellow (Avy/a) mice. The yellow mouse syndrome.

Maturity-onset obesity and elevated circulating insulin levels are characteristic of some, but not all, mice bearing the viable yellow mutation (Avy) at the agouti locus. The expression of the Avy/a genotype in individual mice, which become obese and which remain lean is determined during prenatal development by as yet unidentified conditions in the dam's reproductive tract. One Avy/a phenotype is identified by a mottled yellow coat and characterized by adult obesity, elevated circulating insulin levels, and impaired glucose tolerance. These mice are notably more susceptible to hyperplasia and neoplasia. The alternative Avy/ a phenotype has a pseudoagouti coat, remains lean, is normoinsulinemic and normoglycemic, and in numerous other characteristics resembles congeneic lean black (a/a) littermates. Obese mottled yellow and lean pseudoagouti Avy/a mice differ in capacity to support the growth of ascites cells, in the growth response to castration, and in hepatic glutathione S-transferase activity, erythrocyte fragility, immune function, and susceptibility to Plasmodium yoelii pathogenesis. Our working hypothesis is that the constellation of characteristics, except coat color pattern, which differentiate the obese yellow mice from their lean littermates, is largely a consequence of the elevated circulating insulin levels that induce increased lipogenesis and decreased lipolysis, increased DNA and protein synthesis, increased mitosis in sensitive tissues, and increased proliferation of transformed cells.

Animals↗

PubMedDate not supplied

Immunotoxicity of cephalosporins in mice.

This study was performed in female B6C3F1 mice to confirm previously observed effects of selected cephalosporin antibiotics on nonspecific immunity, and to determine possible effects on specific acquired immunity and host resistance. Mice were treated intravenously with DQ-2556, ceftizoxime or ceftezole at 800 mg/kg/day for 3, 5, or 7 consecutive days. All three compounds increased total serum IgM levels from day 3, but had no effects on total serum IgG levels and the thymus weight. All three cephalosporin antibiotics caused a slight increase in spleen weight and splenic germinal centers were enlarged after 5- or 7-day treatments. Antibody responses to type III pneumococcal polysaccharide (S3), a T-cell-independent immunogen, and sheep red blood cells (SRBC), a T-cell-dependent immunogen, were slightly decreased after 5-day dosings with each compound, and reached significance in DQ-2556 (response to S3) and ceftizoxime (response to S3 and SRBC). None of the tested cephalosporin antibiotics altered delayed-type hypersensitivity to oxazolone or host resistance to Plasmodium yoelii, indicating that the antibiotic-treated mice retained the capacity to mount a multicomponent and sustained protective immune response. These data suggest that although cephalosporins may cause polyclonal expansion of B cells with associated increases in total serum IgM, they do not affect the tested measures of cell-mediated immunity or host resistance. The decreased IgM antibody responses to S3 and SRBC are associated with but not known to be causally related to the concurrent IgM hypergammaglobulinemia.

Animals↗

PubMedDate not supplied

Pattern of response to interstitial hyperthermia and brachytherapy for malignant intracranial tumour: a CT analysis.

Interstitial microwave hyperthermia in combination with iridium-192 brachytherapy has been administered to 23 cases of malignant brain tumours in a phase one clinical trial to assess the feasibility and safety of this treatment. In order to quantify the acute and long-term response of tumour and surrounding brain to this treatment, a morphometric computed tomography scan analysis was performed in 18 evaluable patients. Volumes defined by the outer margin of the contrast-enhancing rim, by the hypodense necrotic region within the enhancing rim and by the surrounding hypodensity region were calculated from computer measurements. Hyperthermia equipment performance (HEP) was calculated for the evaluation of heating. After the treatments, the volume of the inner hypodensity region decreased in seven patients and the volume increased in 11 patients. In five patients, the outer margin of the contrast-enhancing lesion showed an initial increase in volume followed by a decrease and in these patients higher HEP and longer survival were observed significantly. The volume of the surrounding hypodensity region varied following treatments, but in most instances, the region subsequently increased in the interval immediately prior to death. Contribution of heat effect to these changes are discussed and the significance of aggressive heating, which provides transient opening of blood brain barrier, is shown.

Adult↗