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Biomedical subjects

R A Miles

Publications and source records attributed to R A Miles.

10 recordsLinked to original sources
PubMed1994

Pharmacokinetics and endometrial tissue levels of progesterone after administration by intramuscular and vaginal routes: a comparative study.

OBJECTIVE: To determine pharmacokinetic and endometrial effects of vaginally delivered micronized P. DESIGN: Functionally agonadal estrogen-replacement recipients received either micronized P administered vaginally or bi-daily IM injections of P. Hourly blood samples were obtained, from baseline to 6 hours after the initial dose of P and again on simulated cycle day 21 when transvaginal ultrasound (US) measurements and tissue samples of the endometrium were performed. Blood and tissue samples were assayed for P. Endometrial histology, estrogen receptor (ER) and P receptor (PR) contents were evaluated. SETTING: University of Southern California School of Medicine, Los Angeles, California. PARTICIPANTS: Twenty functionally agonadal and four normally ovulating women. MAIN OUTCOME MEASURE: Delivery differences were assessed by [1] endometrial P concentrations; [2] USs; [3] histologic datings; [4] ER and PR contents, and [5] serum P levels. RESULTS: Endometrial P concentrations were higher with vaginally administered P than endometrial concentrations observed in normal ovulatory women or women who consistently had the highest serum P after IM administration (11.50 +/- 2.60 versus 1.40 +/- 0.40 versus 0.30 +/- 0.10 ng/mg protein [36.56 +/- 8.27 versus 4.45 +/- 1.27 versus 0.95 +/- 0.32 nmol/L], respectively). After 7 days of P, no differences between either treatment regimen and control groups were detected by histologic, ultrasonographic, or immunocytochemical receptor analyses. CONCLUSION: Vaginal micronized P enhances P delivery to the uterus compared with a standard IM regimen and results in a synchronous secretory endometrial histology in agonadal women preparing for embryo donation.

Administration, Intravaginal↗
PubMed1993

Evaluating the effect of age on endometrial responsiveness to hormone replacement therapy: a histologic ultrasonographic, and tissue receptor analysis.

OBJECTIVE: Our objective was to characterize the endometria of women of various ages placed on similar estrogen/progesterone replacement regimens prior to attempted donor embryo transfer using histologic, ultrasonographic, and steroid receptor markers in order to determine if advancing age has a detrimental effect on uterine responsiveness to pharmacologic sex steroid replacement therapy. STUDY DESIGN: This was a prospective open clinical trial. Functionally agonadal women aged 25 to 60 years receiving hormone replacement therapy underwent transvaginal ultrasound examination of the uterus followed by a timed endometrial biopsy on artificial cycle day 21. Endometrial histology and estrogen and progesterone receptors were analyzed from biopsy material. Subjects were assigned to three groups according to age: Group I, aged 25 to 39 years (n = 48); Group II, aged 40 to 49 years (n = 61); and Group III, aged 50 to 60 years (n = 13). Endometrial preparation was accomplished in all patients using the same sequential regimen consisting of oral micronized estradiol and intramuscular progesterone. RESULTS: Similar histologic, ultrasonographic, and steroid receptor characteristics were noted in all groups of patients regardless of age. A normal appearing midluteal secretory endometrium was demonstrated histologically in 85% of biopsies. However, 15% of biopsies exhibited intraluminal papillary excrescences within the glands and/or increase in the normal gland-to-stroma ratio. Three patients, one from each group, did not initially respond to replacement therapy and required further treatment. CONCLUSION: Functionally agonadal women exhibit normal or near-normal endometrial responses to sex steroid replacement therapy designed to imitate the natural cycle through the sixth decade of life.

Adult↗
PubMed1992

The ratio of androstenedione:11 beta-hydroxyandrostenedione is an important marker of adrenal androgen excess in women.

OBJECTIVE: To determine if the ratio of serum androstenedione (A):11 beta-hydroxyandrostenedione (OHA) would be helpful in differentiating adrenal from ovarian hyperandrogenism. DESIGN/SETTING: Prospective study of outpatients being evaluated for hyperandrogenism. PATIENTS/PARTICIPANTS: Normal women (n = 27), those with hyperandrogenic chronic anovulation (n = 25), and 7 with adult onset of congenital adrenal hyperplasia (CAH) because of 21-hydroxylase deficiency. INTERVENTIONS: Fasting serum between 8:00 A.M. and 9:00 A.M. Patients with hyperandrogenic chronic anovulation and CAH received dexamethasone (DEX) 2 mg for 7 days. MAIN OUTCOME MEASURES: Serum testosterone (T), unbound T, dehydroepiandrosterone sulfate (DHEAS), A, and 11 beta-OHA by radioimmunoassay. RESULTS: Serum 11 beta-OHA and DHEAS were elevated in 52% and 40% of patients with hyperandrogenic chronic anovulation and in 7 of 7 and 1 of 7 patients with CAH. The ratio of A:11 beta-OHA was significantly higher (P less than 0.05) in hyperandrogenic chronic anovulation and significantly lower (P less than 0.05) in CAH compared with controls. Serum A:11 beta-OHA correlated with T (r = 0.58, P less than 0.05). The ratios of A:11 beta-OHA were similar and significantly lower in CAH and hyperandrogenic chronic anovulation patients who were DEX sensitive compared with those who were not DEX sensitive. The ratio correlated with the percentage suppression of T, unbound T, and A after DEX (P less than 0.01). There were no differences with measurements of DHEAS and 11 beta-OHA. Using the mean ratio of controls (1.3) as a cutoff value, the sensitivity of the A:11 beta-OHA in detecting adrenal hyperandrogenism, as assessed by DEX sensitivity, was 100%, the specificity was 84%, and the predictive value was 67%. CONCLUSIONS: The ratio of A:11 beta-OHA appears to be an excellent marker for identifying patients with adrenal hyperandrogenism and CAH.

Adolescent↗
PubMed1992

Cutaneous application of an androstenedione gel as an in vivo test of 5 alpha-reductase activity in women.

OBJECTIVE: Assessment of an in vivo test for 5 alpha-reductase activity using serum markers, 5 alpha-androstane-3 alpha,17 beta-diol glucuronide and androsterone glucuronide, after the cutaneous application of androstenedione (A). DESIGN: An A gel was applied for 6 days to the skin of normal women, male volunteers, and hirsute and nonhirsute patients with polycystic ovarian syndrome (PCOS). Blood samples were obtained at baseline and on day 6 of the A gel application. Blood samples were assayed for A, 5 alpha-androstane-3 alpha,17 beta-diol glucuronide, and androsterone glucuronide. In three hirsute women, the protocol was followed before and after receiving an oral contraceptive (OC) and spironolactone 200 mg/d for 3 months. SETTING: The study was performed in the outpatient clinic of the Division of Reproductive Endocrinology and Infertility, Women's Hospital of the Los Angeles County and University of Southern California Medical Center in Los Angeles, California. PATIENTS, PARTICIPANTS: A total of eight nonhirsute patients with PCOS, seven hirsute patients with PCOS, and six male volunteers were enrolled in the study. Five normal women served as a control group. MAIN OUTCOME MEASURE: Serum A increased after 6 days by a similar magnitude in all groups. Serum androsterone glucuronide showed a significant increase from baseline only in the hirsute group (P < 0.03), whereas the increase in 5 alpha-androstane-3 alpha,17 beta-diol glucuronide was not statistically significant. RESULTS: The ratio of the increases in serum androsterone glucuronide over serum A was significantly higher in the hirsute group (P < 0.02). In the three hirsute patients who were placed on an OC and spironolactone, serum 5 alpha-androstane-3 alpha,17 beta-diol glucuronide and androsterone glucuronide decreased after 3 months and did not increase with application of the gel for another 6 days. CONCLUSION: The cutaneous application of A provides a useful assessment of in vivo 5 alpha-reductase activity. However, because we found that A absorption varied considerably (30% to 62%), we suggest that this in vivo test may not provide more information than baseline determinations of 5 alpha-androstane-3 alpha,17 beta-diol glucuronide and androsterone glucuronide. It may, however, be useful as a parameter for assessing the effectiveness of various treatment regimens for hirsutism.

Administration, Cutaneous↗
PubMed1976

The Montenegro reaction in guinea pigs infected by Leishmania enriettii and the effect of antigens prepared from various Leishmania isolates.

All antigens (leishmanin) prepared from nine isolates of Leishmania gave positive skin tests in guinea pigs infected with L. enriettii. However, variation in potency was observed and ascribed to batch variation. It is recommended that biological testing of leishmanin is considered before use in field surveys or as an aid to clinical diagnosis.

Animals↗