Biomedical subjects

P W Houben

Publications and source records attributed to P W Houben.

7 recordsLinked to original sources

PubMed2001

Ki-67 immunoquantitation in cervical intraepithelial neoplasia (CIN): a sensitive marker for grading.

The aim of this study was to assess the value of Ki-67 immunoquantitation with a computerized image analysis system for grading support in cervical intraepithelial neoplasia (CIN). Sixty-five 'blind' consensus biopsies (23 CIN 1, 22 CIN 2, and 20 CIN 3) were used as a learning set. Measurements were done in the carefully selected most severely dysplastic part of the epithelium of each CIN case. The resulting discriminating combination of quantitative features was then prospectively applied on 121 new biopsies (test set) and compared with the classical CIN grade assessed routinely by six different pathologists and with the blind review grades assessed by two experienced pathologists. In the learning set of 65 cases, a jack-knifed stepwise discriminant analysis showed that the 90th percentile of the stratification index and the number of positive nuclei per 100 microm basal membrane are the best discriminating set of features to distinguish the three CIN grades at the same time. With these features, two CIN 1 cases were 'misclassified' as CIN 2 and nine CIN 2 cases as CIN 3. Overall agreement, therefore, was only 83%. However, recut of the paraffin blocks in the two 'misclassified' CIN 1 cases revealed CIN 2 in the first and CIN 3 in the other, while the other CIN 1 cases that were correctly classified with Ki-67 quantitation remained CIN 1. Likewise, nine CIN 2 cases were misclassified as CIN 3, but in two of these nine cases histological follow-up clearly indicated CIN 3. Agreement may thus be higher than the 83% in the learning set suggests. In the subsequent prospective evaluation on 121 routine CIN cases (test set), agreement between routine CIN grades (by six independent different pathologists) and quantitative Ki-67 classification was 78%. However, when compared with the blind review CIN grades of two expert pathologists, agreement was 97% and sensitivity, specificity, and positive and negative predictive value were very high. It is concluded that Ki-67 immunoquantitation is a useful diagnostic adjunct to distinguish different CIN grades and may also be a sensitive biological indicator of progression of seemingly low-grade CIN.

Antigens, Neoplasm↗

PubMed2001

Prospective multicenter evaluation of the morphometric D-score for prediction of the outcome of endometrial hyperplasias.

Prospective multicenter evaluation of the WHO classification and the morphometric D-score to predict endometrial hyperplasia cancer progression. In 132 endometrial hyperplasias WHO classification was performed by two experienced gynecologic pathologists. The D-score was assessed blindly by technicians in a routine diagnostic setting. Development of endometrial carcinoma during a 1-10-year follow-up was used as the end point. Eleven of 132 patients (8%), 10 of 61 (16%) atypical hyperplasias, and 1 of 71 (1%) nonatypical hyperplasias developed cancer. Twenty-six curettings had a D-score < or = 0 ("unfavorable" or endometrial intraepithelial neoplasia) of which 10 (38%) developed cancer. None of the 86 cases with a D-score > 1 ("favorable") and one of the 20 (5%) cases with 0 < D-score < or = 1 ("uncertain") developed cancer. Sensitivity of the D-score was 100%, specificity 82%, the positive and negative predictive values were 38% and 100%, respectively. These values are similar to those in three prior retrospective D-score studies but higher than the WHO values (which are 91%, 58%, 16%, and 99%, respectively). The D-score in endometrial hyperplasias is a more sensitive and specific marker for cancer prediction than the WHO classification, can be assessed in a routine clinical setting on standard hematoxylin and eosin sections (15-30 minutes per case), and is highly reproducible and cost-effective (U.S. $50 per case).

Adult↗

PubMed2001

A 1-year comparison of the efficacy and clinical tolerance in postmenopausal women of two hormone replacement therapies containing estradiol in combination with either norgestrel or trimegestone.

This double-blind, randomized, multi-center study compared the efficacy and clinical tolerance of a combined formulation containing 2 mg estradiol (E2) and 0.5 mg trimegestone (TMG) with a standard hormone replacement therapy containing estradiol valerate (E2V) and norgestrel (NG) in the treatment of climacteric symptoms. The study was conducted over 13 cycles, each of 28 days, and involved 634 subjects, of whom 481 completed the study. The primary efficacy variable was the percentage of subjects who showed at least a 50% reduction from baseline in the mean daily number of hot flushes in cycle 3. This was observed in 98.5% of the subjects in the E2 + TMG group and 93.3% of the subjects in the E2V + NG group (95% confidence interval of the difference, -8.6, -1.9). Significant differences in favor of the E2 + TMG combination were observed in the reduction in the mean daily number and severity of hot flushes, and in the percentage of subjects who had hot flushes at baseline but no hot flushes during treatment. There were no significant differences between the treatments in the Kupperman index and in urogenital signs or symptoms. Treatment with the E2 + TMG combination was well tolerated and the incidences of adverse events were similar in the two treatment groups. Breast pain was the main adverse event, possibly related to treatment that resulted in discontinuation. The mean number of bleeding days per cycle was significantly lower with the E2 + TMG combination than with the E2V + NG combination. The incidences of endometrial hyperplasia were low and comparable in both treatment groups. It was concluded that the E2 + TMG combination was either equivalent or superior to the E2V + NG combination in the treatment of hot flushes and other climacteric symptoms, and that its bleeding profile was favorable.

Double-Blind Method↗

PubMed1987

The differential regulation of the intranuclear progestin in mouse kidney and prostate-seminal vesicles.

This study was designed to confirm the identity of the enzyme involved in the appearance of a nuclear metabolite of 6a-methyl progesterone (6MP) in mouse kidney but not in prostate-seminal vesicle. 6MP and progesterone competed for metabolism by the kidney enzyme. Using progesterone as substrate, the results of recrystallization of the product with 20a-hydroxy progesterone supported the identification of the enzyme as 20a-hydroxysteroid dehydrogenase (20aHSD). The enzyme had a substrate specificity similar to that reported for 20aHSD in other tissues. Renal enzyme activity was higher in female than in male CD-1 mice while activity was generally lower and without a sex difference in a random bred colony. Renal enzyme activity varied slightly with the estrous cycle, being highest at proestrus and lowest on day 2 of diestrus. Little enzyme activity was detected in prostate-seminal vesicles. It appears that 20aHSD is an important factor in regulating the differential presence of the 20a-metabolite of 6MP in kidney and prostate-seminal vesicle nuclei.

20-Hydroxysteroid Dehydrogenases↗

PubMed1986

Differences in the androgen response between two mouse species.

Renal weight and beta-glucuronidase activity are two of several well-characterized androgen-responsive parameters in Mus musculus. A similar sexual dimorphism was not reported for a second mouse species, Mus caroli, however. Since this was not associated with a general absence of androgen action, we considered whether a localized defect in androgen receptors or a difference in renal androgen-responsive endpoints in the two species existed. Only minor differences in the characteristics of renal androgen receptors from the two species were found when they were analyzed by two different methods. These differences were not thought to be sufficient to account for the apparent renal androgen unresponsiveness. No differences were found in androgen receptors from brain. Subsequently, a third renal endpoint, ornithine decarboxylase activity, was found to respond to androgen stimulation in Mus caroli. Control of renal androgen action in these two mouse species thus differs at the level of genetic regulatory elements.

Animals↗

PubMed1985

Receptor binding of 6 alpha-methylprogesterone in mouse kidney.

6 alpha-Methylprogesterone (6MP) is an androgenic progestin that binds to the androgen receptor. However, results from an in vivo study suggested that 6MP was also bound by a second receptor. In the present study, we found that 6MP was bound in kidney cytosol from adrenalectomized/ovariectomized female mice as well as Tfm/Y mice, which lack androgen receptors. 6MP was bound with high affinity (Kd = 1.2 X 10(-8) M) by a binder that was present in 7-8 times greater concentration than the androgen receptor and had the specificity of a glucocorticoid receptor. 6MP was bound with similar specificity in liver cytosol. These data indicate that, despite its androgenic effects, 6MP binds primarily to a glucocorticoid receptor in mouse kidney.

Animals↗

PubMed1984

Two forms of ornithine decarboxylase activity in mouse kidney.

Renal ornithine decarboxylase (ODC) activity was evaluated in normal female, male, testosterone-treated female and androgen-insensitive Tfm/Y mice for its heat sensitivity and in vivo half-life. ODC activity in normal female kidney consisted of 2 forms which differed in their heat sensitivity at 46 degrees C. Androgens, either endogenous in normal males or administered exogenously to females, induced primarily the heat-sensitive form. Results from mixing experiments indicated that the heat-sensitive form represented a change in the property of the ODC activity rather than a change in cytoplasmic factors. The in vivo half-life of ODC activity was increased slightly in males and short-term androgen-treated females over normal females and was markedly increased by prolonged androgen treatment. In vivo, the androgen-induced, heat-sensitive form decayed faster than did the heat-resistant form. We conclude that androgens have specific effects on both the amount as well as the biochemical properties of ODC activity in mouse kidney.

Animals↗