Seasonal variation in serum testosterone, testicular volume, and semen characteristics in the coyote (Canis latrans).

The coyote is a seasonally breeding mammal, with most copulations occurring between December and April (depending on location). The objective of this study was to characterize seasonal changes in serum testosterone concentrations, testicular volume, and ejaculate quantity and quality in captive male coyotes. There were seasonal differences in testicular volume, with the greatest volume (20.2+/-5.4cm2), mean+/-S.E.M.) in February, corresponding with peak breeding season. Circulating serum testosterone concentrations peaked (3.31+/-0.9 ng/mL) during January and were positively correlated (P< or =0.001, r=0.413) with testicular volume. Ejaculate volume (1.67+/-0.4 mL) and sperm concentration (549.2 x 10(6)+/-297.7 spermatozoa/mL) both peaked during January and February, consistent with the height of the breeding season. Ejaculate volume and sperm concentrations were positively correlated with testicular size (r=0.679, P< or =0.001 and r=0.499, P< or =0.001, respectively) and with serum testosterone concentrations (r=0.368, P< or =0.01 and r=0.208, P< or =0.05). Progressively motile, viable, and morphologically normal spermatozoa fluctuated seasonally, peaked (90.4+/-4.5, 84.8+/-4.1, and 87.9+/-2.9%) during the breeding season, and then subsequently declined (period of aspermatogenesis). All three of these end points were positively correlated with testicular size (r=0.589, P< or =0.001; r=0.586, P< or =0.001; and r=0.469; P< or =0.001) and serum testosterone (r=0.167, P< or =0.05; r=0.190, P< or =0.05; and r=0.221, P< or =0.01). In conclusion, there were intricate relationships among testosterone concentrations, testicular volume, and the production of both functionally intact and morphologically normal spermatozoa.

False negative rate of cervical cytologic smear screening as determined by rapid rescreening.

OBJECTIVE: To determine the reliability of the false negative rate (FNR) of cervical cytologic smear screening by rapid rescreening. STUDY DESIGN: A test set of 401 cases (311 originally diagnosed as negative, 74 as atypical squamous cells of undetermined significance [ASCUS], 14 as low grade squamous intraepithelial lesion [LSIL] and 2 as high grade squamous intraepithelial lesion [HSIL]) were rapidly (30 seconds each) rescreened by five cytotechnologists with no prior experience in rapid rescreening, and the FNRs of rapid rescreening and primary screening were determined. These results were compared with each other and with the FNR of primary screening as determined by routine rescreening of all cases with no time limit. RESULTS: All five observers detected a different group of abnormal cases; only 9% of all cases originally diagnosed as ASCUS or worse and 43% of all cases diagnosed as LSIL or worse were detected by all five observers. Nevertheless, using ASCUS as the threshold for an abnormal result, the FNR of rapid rescreening fell into a relatively narrow range, 61-74% (mean, 68.2 +/- 5.0); using LSIL as the threshold resulted in FNRs of rapid rescreening between 25% and 38% (30.0 +/- 4.7). Each observer, using rapid rescreening, detected between one and three false negative cases; routine rescreening of all cases without a time limit detected five cases. The FNR of cervical cytologic smear screening, as determined by rapid rescreening, was 18.4 +/- 6.1% as compared with 14.8% by routine rescreening without a time limit. CONCLUSION: The FNR of rapid rescreening is relatively reproducible even though the individual cases identified varied between reviewers. The FNR of rapid rescreening is similar to that of routine rescreening. Rapid prescreening may be the most logistically simple method to determine the true FNR of a laboratory.

Performance characteristics of rapid (30-second) prescreening. Implications for calculating the false-negative rate and comparison with other quality assurance techniques.

Rapid (30-second) prescreening of cervicovaginal smears can be used to detect false-negative cases and determine the false-negative rate of primary screening, but the performance characteristics have not been evaluated fully. A test set of 242 cases including 80 originally false-negative cases were rapidly screened by 4 different cytotechnologists on 2 occasions. Intraobserver and interobserver reproducibility were good. Median specificity for each round of observations was 89% (range, 30%-96%). Median sensitivity for all true-positive cases was 78% (range, 63%-97%); for all false-negative cases it was 59% (range, 38%-89%). The relative sensitivity of rapid screening for true-positive and false-negative cases varied with the diagnosis. Rapid screening detected almost the same percentage of false-negative cases of atypical squamous cells of uncertain significance (ASCUS) as true-positive ASCUS cases (median ratio, 1.12; range, 0.72-1.52). The median ratio of false-negative to true-positive ASCUS cases was significantly different than the ratio for low-grade plus high-grade squamous intraepithelial lesions (0.68; range, 0.50-0.96). Although performance varies between individuals, in this test population the reproducibility, specificity, and sensitivity were good. Because it detects more false-negative cases at a lower cost per case than routine rescreening, rapid prescreening should be considered as an alternative to current quality control measures.

Adenocarcinoma in situ in cervical smears with a small cell (endometrioid) pattern: distinction from cells directly sampled from the upper endocervical canal or lower segment of the endometrium.

Adenocarcinoma in situ (AIS) with small, endometrioid cells in cervicovaginal smears, is a source of false-negative diagnoses because of the difficulty in distinguishing these cells from endometrial cells of the lower uterine segment or benign cells from the upper endocervical canal. This study was designed to elucidate the most useful criteria for this distinction. Three observers blinded to the actual diagnoses reviewed 29 preselected cases (AIS, 17; benign, 12) that had originally caused diagnostic difficulty. Each observer made a diagnosis and evaluated 15 preselected diagnostic criteria. All 3 observers agreed on the correct diagnosis in 19 (66%) of 29 cases, and at least 2 observers agreed on the correct diagnosis in 27 (93%) of 29 cases. No case was misdiagnosed by all 3 observers. The most useful criteria for the diagnosis of AIS are a predominance of groups with marked crowding, focal feathering, nuclear hyperchromatism with coarsening of chromatin, and occasional mitotic figures. Sheets of cells, endometrial tubules, and endometrial stroma favor a benign diagnosis. Although 12 (14%) of 87 possible diagnoses were erroneous, well-preserved, small, endometrioid AIS cells can be identified correctly on cervical smears and distinguished from epithelium from the lower uterine segment and high endocervical canal in most cases using the aforementioned criteria.

Koilocytotic atypia in Papanicolaou smears. Reproducibility and biopsy correlations.

BACKGROUND: It would be useful if cervical smears containing koilocytes alone could be reliably separated from those containing other forms of nuclear atypia within the spectrum of low grade squamous intraepithelial lesions (LSIL) and that this separation was predictive of differences in biopsy follow-up. In this article, the authors sought to test this possibility. METHODS: Consecutive smears diagnosed as LSIL from 140 patients who had follow-up colposcopic biopsies were reviewed independently by three observers. The inter- and intraobserver reproducibility in diagnosing smears with koilocytes alone was assessed by the kappa statistic. Comparison of each reviewer's cytologic diagnosis with a reviewed biopsy diagnosis was assessed using chi-square analysis. The quantity of abnormal cells was compared with the presence or absence of a lesion on biopsy. RESULTS: Kappa values for any 2 observers agreeing on koilocytosis as a separate category ranged from 0.22-0.47 (poor to good). Intraobserver reproducibility across all cytologic categories ranged from 0.35-0.62 (poor to good). A cytologic diagnosis of koilocytosis predicted a lower rate of high grade SIL (HSIL) on initial biopsy for one of the observers, but not for the other two. Koilocytosis did not predict a lower rate of LSIL on initial biopsy or HSIL in follow-up biopsies for any observer. The quantity of cells on the initial smear did not correlate with a lesion on biopsy. CONCLUSIONS: Separation of LSIL into two diagnostic categories is not feasible because of its poor cytologic reproducibility and inability to predict differences in biopsy diagnosis. The quantity of abnormal cells in LSIL is not predictive of the detection of a lesion on biopsy.

Papanicolaou smear sensitivity for adenocarcinoma in situ of the cervix. A study of 34 cases.

The sensitivity of cervical smears for adenocarcinoma in situ (AIS) is not known, nor is it known whether false-negative smears are due to sampling or to screening or interpretive errors. In 16 of 34 patients with AIS, 38 negative smears were reported 2 weeks to 7 years before biopsy. Thirty-one of these negative smears were rescreened, and 17 (55%) were retrospectively diagnosed as abnormal. Ten of the 17 had numerous well-preserved AIS cells: 5 with very small, crowded AIS cells, possibly originally mistaken for endometrial cells, and 5 with large groups in which AIS cells resembled reactive endocervical cells. Four smears were confirmed sampling errors. The sensitivity of cervical smears for AIS was 55% to 72%. Improved sampling of the endocervical canal offers cytologists the opportunity to diagnose AIS. This study demonstrates that this opportunity may not be fully exploited. Small "endometrioid" AIS cells and AIS cells resembling reactive endocervical cells may be mistaken for benign cells, thus decreasing sensitivity.

A more accurate measure of the false-negative rate of Papanicolaou smear screening is obtained by determining the false-negative rate of the rescreening process.

BACKGROUND: The false-negative rate (FNR), or fraction, of Papanicolaou (Pap) smear screening has been proposed as a useful quality assessment measure. The FNR should account for the FNR of the rescreening process itself. The authors measured the FNR of the rescreening process by rescreening a set of abnormal smears. METHODS: A randomly selected group of negative (150) and abnormal (91) smears were rescreened in a blinded fashion. A diagnosis of atypical squamous cells of undetermined significance (ASCUS) or worse was used as a positive (abnormal) result. All discrepancies were confirmed by consensus review. The true FNR of screening Pap smears was calculated as: true FNR = calculated FNR/(1-FNR of rescreening). RESULTS: When rescreened, 17 originally negative cases were interpreted as ASCUS and 5 as unsatisfactory. Twenty-three originally abnormal cases (22 ASCUS and 1 low grade squamous intraepithelial lesion) were interpreted as negative. After consensus review, only 1 of the originally negative cases was believed to be ASCUS and 1 unsatisfactory; 18 of the 23 originally abnormal cases were believed to be rescreening errors and 5 of the 23 originally abnormal cases were believed to be false-positives. The FNR of Pap smear screening as traditionally calculated was 6.1%, which was slightly less than the laboratory's usual FNR. The FNR of review screening was 20.9%. The true FNR of Pap smear screening was 7.8% and the false-positive rate was 0.6%. CONCLUSIONS: The FNR of rescreening is not insubstantial. It can and should be measured by rescreening abnormal smears, and when taken into account yields a more accurate measure of the FNR of Pap smear screening.