Numerical oxidation model for gamma radiation-sterilized UHMWPE: consideration of dose-depth profile.

Gamma sterilization of UHMWPE hip and knee joint replacement components secondarily creates free radicals along the polymer chains. Though crosslinking between radicals may improve mechanical properties, typical post-irradiation environments (air shelf storage or in vivo service) may instead favor scission reactions with oxygen from the surroundings. As such aging of irradiated UHMWPE joint replacement components has important consequences such as osteolysis, increased insight has been sought through descriptive models of this oxidation process. The quantitative numerical model presented here accounts for a free radical concentration that varies with position (because of irradiation dose-depth profile) and time (because of free radical decay through crosslinking). A moving front of diffusing O(2) is allowed to traverse the UHMWPE medium containing depth- and time-dependent free radical concentration, and these diffusing molecules react with available free radicals persisting at the front. This model's capabilities are illustrated in three examples of irradiated UHMWPE aging behavior: In room-temperature air (shelf-aging), in atmospheres of augmented oxygen partial pressure and temperature intended to accelerate aging while otherwise remaining simulative of real-time aging; and following post-irradiation vacuum storage intended to consume free radicals through complete crosslinking, but often performed to an incomplete extent.

A novel constrained acetabular liner design with increased range of motion.

One treatment strategy for recurrent dislocation after total hip arthroplasty is the use of a constrained acetabular component. A major drawback of currently available constrained components is the limited range of motion (ROM). We present a novel constrained component that employs a monopolar, highly cross-linked polyethylene liner with cutouts oriented to allow increased ROM, while maintaining constraint against dislocation. ROM and lever-out tests comparing this novel design with a conventional constrained component showed that the cutaway monopolar component allowed ROM substantially greater than a currently available design. The lever-out torque for the cutaway monopolar constrained component was 243% higher than the conventional constrained component. This novel constrained acetabular component offers promise for providing excellent constraint against dislocation, while maintaining a wide ROM.

Biomarker correlations of urinary 2,4-D levels in foresters: genomic instability and endocrine disruption.

Forest pesticide applicators constitute a unique pesticide use group. Aerial, mechanical-ground, and focal weed control by application of herbicides, in particular chlorophenoxy herbicides, yield diverse exposure scenarios. In the present work, we analyzed aberrations in G-banded chromosomes, reproductive hormone levels, and polymerase chain reaction-based V(D)J rearrangement frequencies in applicators whose exposures were mostly limited to chlorophenoxy herbicides. Data from appliers where chlorophenoxy use was less frequent were also examined. The biomarker outcome data were compared to urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D) obtained at the time of maximum 2,4-D use. Further comparisons of outcome data were made to the total volume of herbicides applied during the entire pesticide-use season.Twenty-four applicators and 15 minimally exposed foresters (control) subjects were studied. Categorized by applicator method, men who used a hand-held, backpack sprayer in their applications showed the highest average level (453.6 ppb) of 2,4-D in urine. Serum luteinizing hormone (LH) values were correlated with urinary 2,4-D levels, but follicle-stimulating hormone and free and total testosterone were not. At the height of the application season; 6/7 backpack sprayers, 3/4 applicators who used multinozzle mechanical (boom) sprayers, 4/8 aerial applicators, and 2/5 skidder-radiarc (closed cab) appliers had two or more V(D)J region rearrangements per microgram of DNA. Only 5 of 15 minimally exposed (control) foresters had two or more rearrangements, and 3 of these 5 subjects demonstrated detectable levels of 2,4-D in the urine. Only 8/24 DNA samples obtained from the exposed group 10 months or more after their last chlorophenoxy use had two rearrangements per microgram of DNA, suggesting that the exposure-related effects observed were reversible and temporary. Although urinary 2,4-D levels were not correlated with chromosome aberration frequency, chromosome aberration frequencies were correlated with the total volume of herbicides applied, including products other than 2,4-D. In summary, herbicide applicators with high urinary levels of 2,4-D (backpack and boom spray applications) exhibited elevated LH levels. They also exhibited altered genomic stability as measured by V(D)J rearrangement frequency, which appears reversible months after peak exposure. Though highly detailed, the limited sample size warrants cautious interpretation of the data.

Herbicides and adjuvants: an evolving view.

The present report examines the in vitro genotoxicity (micronucleus assay) of herbicides and adjuvants and reports on an in vivo human study on potential endocrine effects of pesticides, including herbicides. Adjuvants are used in conjunction with 2,4-dichlorophenoxy acetic acid (2,4-D) and other herbicides. Earlier pesticide applier survey results (n = 709) show that 59% of the applicators used adjuvants, and the majority of this group used paraffinic oils and/or surfactant mixtures. As a beginning effort to explore the role of adjuvants and herbicides in hormonally based reproductive effects, a prospective, controlled study was performed to analyze blood specimens from three different exposure groups (applicators using herbicides only; applicators using both herbicides and insecticides; and applicators using fumigants in addition to herbicides and insecticides; and a control group composed of other agricultural workers including organic farmers). The applicators and controls were age- and smoking-matched. Study subjects (n = 78) were tested before, during, and after completion of pesticide application season for the effects of pesticide products on hormone levels in the bloodstream. Of the applicator exposure groups examined, only the herbicide group showed significant endocrinologic differences from controls. Free testosterone levels were significantly elevated in post-season measurements (p = 0.032), and follicle-stimulating hormone (FSH) was significantly decreased at the height of the season (p = 0.016) and in the post-season (p = 0.010) as compared to controls. These endocrinologic findings are discussed in terms of their possible relationship to potential endocrine effects of herbicides, herbicide contaminants, and adjuvants. In vitro genotoxicity examination compared four different commercially available surfactant mixtures with 12 different commercial herbicide products, including six different chlorophenoxy herbicides. Only one herbicide yielded a significant dose-response curve. All four adjuvants showed positive dose-response effects. These preliminary data suggest that adjuvants are not inert but are toxicologically active components added to herbicide mixtures. Whether adjuvant toxicant effects are additive or are independent of herbicide effects is poorly understood.

Pesticide appliers with mixed pesticide exposure: G-banded analysis and possible relationship to non-Hodgkin's lymphoma.

To further investigate the possible relationships between agricultural pesticide exposure and the increased risk of non-Hodgkin's Lymphoma among farm workers in the north central United States, we performed G-banded chromosome analyses of peripheral blood from workers classified according to primary types of pesticide exposure: herbicides (n = 20), insecticides (n = 18), fumigants (n = 23), and occupationally unexposed controls (n = 33). Significantly increased rearrangement frequencies were demonstrated in fumigant and insecticide appliers compared to control subjects. At certain chromosome bands there were significant excesses of breaks observed in pesticide appliers, but no breaks were observed in controls. Some of these bands contained genes with potential implications for cancer risk, including oncogenes and genes involved in tumor suppression and apoptosis. Of particular interest with regard to lymphoma risk were the excess rearrangement and breaks involving band 14q32 in fumigant appliers and the excess breaks involving band 18q21 in herbicide appliers; translocations linking 14q32 and 18q21 are the most common rearrangements observed in non-Hodgkin's lymphoma patients. The potential pathobiological relevance of these cytogenetic events warrants additional investigation at the molecular level.

Pregnancy in patients with cystic fibrosis.

As more patients with cystic fibrosis reach adulthood, questions arise about the potential hazards of pregnancy. We reviewed the medical records of eight women with cystic fibrosis who had a total of 11 completed pregnancies and had been evaluated within 1 year before conception. In five women (Group 1), the overall maternal condition was little affected by the pregnancy, and in three women (Group 2), the mother's condition deteriorated during and after pregnancy and did not return to the pregravid state. With regard to pregravid status, significant differences between patients in Group 1 and Group 2 were found in Shwachman-Kulczycki clinical scores, weight for height values, Brasfield chest radiograph scores, and pulmonary function. A quantitative assessment of pregravid nutritional and pulmonary status is useful in counseling women with cystic fibrosis about the risk of pregnancy.

Cimetidine and the immune response. I. In vivo augmentation of nonspecific and specific immune response.

Cimetidine is a commonly prescribed histamine antagonist useful in the treatment of peptic ulcer disease. Histamine receptors are found on suppressor T cells and therefore we expected to observe enhanced immune responsiveness in animals treated with this drug. Mice given daily subcutaneous injections of cimetidine (25 or 100 mg/kg) were found to produce approximately twice as much specific antibody in response to tetanus toxoid immunization. Furthermore, mitogen-stimulated splenocytes from cimetidine-treated animals proliferated to a greater extent and produced more immunoglobulin in vitro than controls. These observations offer direct in vivo evidence for immunomodulation by cimetidine.