Sperm abnormalities associated with high copper levels in impala (Aepyceros melampus) in the Kruger National Park, South Africa.

The morphology of spermatozoa may be affected by very low concentrations of pollutants in the environment, and sublethal effects of toxic substances can be detected by studying the sperm of an animal. Sperm were collected from 50 impala (Aepyceros melampus) from a conservation area in South Africa and studied ultramicroscopically. Thirty-two samples were obtained from animals close to a copper mine, while 18 represented animals from an unpolluted area and held in captivity. Liver samples from all these animals were analyzed for their copper content. The findings from 12 animals kept in captivity and fed on a diet to which copper was added correlated with the findings from the field study. The general condition of the animals as expressed by the fat content of the bone marrow from the area exposed to copper contamination was affected detrimentally in comparison to the animals from the uncontaminated area. High percentages of sperm with neck vacuoles were found in all animals with high liver copper levels. A statistically significant correlation is demonstrated between the percentage of impala sperm with vacuoles in the neck region and the copper concentrations in this group of animals.

Primary combined malignant melanoma and ductal carcinoma of the breast. A report of two cases.

BACKGROUND: Tumors consisting of a combination of malignant melanoma and carcinoma are very rare. The authors report two such cases occurring as primary breast tumors. METHODS: The breast tumors were analyzed by histologic, immunohistochemical, and ultrastructural techniques. RESULTS: Histologically, the tumors were composed of a closely related admixture of ductal adenocarcinoma and malignant melanoma with abundant melanin pigment. Ductal carcinoma in situ was identified in both cases, confirming their origin in the breast. In both tumors, double-labeling immunohistochemistry showed that the epithelial component was immunoreactive for cytokeratin, the melanoma component was immunoreactive for HMB45, and both components were immunoreactive for S-100 protein. Immunostains for estrogen and progesterone receptors were negative in both tumors. Electron microscopy demonstrated glandular lumens and junctional complexes in the epithelial component and melanosomes and premelanosomes in the melanoma component. In one of the cases, rare tumor cells contained both premelanosomes and desmosomes. CONCLUSIONS: Combined malignant melanoma and carcinoma is a rare tumor. Only a handful of cases have been reported. The authors report two such cases occurring as primary tumors of the breast. The histology of the tumors revealed a closely related admixture of pigmented malignant melanoma and ductal carcinoma. Double-labeling immunohistochemistry showed that cytokeratin and HMB45 were expressed in the tumors, but not within the same cells. The authors propose describing this type of lesion as a single tumor of breast origin with bidirectional differentiation.

Disposition of 3-hydroxyquinidine in patients receiving initial intravenous quinidine gluconate for electrophysiology testing of ventricular tachycardia.

The formation rate constant and elimination rate constant for 3-hydroxyquinidine were determined in eight patients with ventricular tachycardia. These two parameters (mean +/- SD) were found to be 0.784 +/- 0.202 and 0.042 +/- 0.058 h-1, respectively. Coefficients of determination for the computer-generated line of best fit for serum concentration-time data were 0.986 +/- 0.008. Patients received two infusions of quinidine gluconate 5 mg/kg over 30 minutes separated by a 20-30 minute electrophysiologic testing period. Unbound and total 3-hydroxyquinidine concentrations were also determined. Among the eight patients, 3-hydroxyquinidine was 61.9 percent bound. Studies in healthy volunteers had shown 50 percent binding. Linear regression of unbound and total 3-hydroxyquinidine was described by the equation Y = 0.3814X-1.448, r = 0.813. Although half-lives of 3.5-12.4 hours had been reported in healthy volunteers, prolonged half-lives were observed in all but two of our arrhythmia patients.

Comparison of disposition values obtained by two assay methods for quinidine gluconate in patients with ventricular tachycardia.

Eight patients with previously untreated ventricular tachycardia, age 48.54 +/- 28.02 years (mean +/- SD), were enrolled in a protocol evaluating the disposition of quinidine gluconate as determined by two assay methods. Patients received two infusions of 5 mg/kg over 30 minutes separated by 20-30 (24.9 +/- 4.0) minutes of electrophysiologic testing. Blood samples were obtained at 0.17 hours and just prior to the second infusion, and then at 0.17, 0.25, 0.33, 1.0, 6.0, 12.0, and 24.0 hours after the second infusion. Paired serum samples were assayed for quinidine concentrations by fluorescence polarization immunoassay and high-performance liquid chromatography. The two assays compared well, with a linear regression equation of Y = 0.927X + 0.247 with a correlation coefficient of 0.985. With the exception of the beta elimination rate constant and beta distribution volume, t test comparison of disposition values demonstrated no significant difference. Differences in the estimates of the beta elimination rate constant reflected differences in the two methods and indicated that even though both assays were comparable, subtle differences in specificity could be reflected in significant differences in this variable.