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Biomedical subjects

A J Friedman

Publications and source records attributed to A J Friedman.

At least 73 records · Page 4Linked to original sources

Sextuplet pregnancy after human menopausal gonadotropin superovulation and intrauterine insemination. A case report.

Sextuplet pregnancy occurred after human menopausal gonadotropin ovulation induction, intrauterine insemination and human chorionic gonadotropin support in the luteal phase. The patient's peak serum estradiol concentration was 861 pg/mL, and ultrasound monitoring demonstrated only one follicle greater than 11 mm in diameter. The possibility of high-order multiple birth exists despite intensive monitoring efforts for this therapy.

Adult↗

Fibroid and myometrial steroid receptors in women treated with gonadotropin-releasing hormone agonist leuprolide acetate.

The reduction in uterine and fibroid volume associated with the chronic administration of a gonadotropin-releasing hormone agonist (GnRH-a) is thought to be secondary to the analogue induced hypoestrogenic state. Our hypothesis was that the concentration of bioactive estrogen receptors (ER) and progesterone receptors (PR) may be important in the regulation of fibroid growth. The purpose of this study was to determine ER and PR content in fibroids and myometria from women pretreated with GnRH-a compared with controls. Tissue was obtained from 20 premenopausal women with uterine fibroids who were randomized to receive either leuprolide acetate depot, 3.75 mg intramuscularly every 28 days for four injections (n = 10) or placebo (n = 10) before myomectomy. The mean fibroid ER and PR content was significantly greater than the mean myometrial ER and PR content. The mean fibroid ER content for GnRH-a-treated patients was significantly greater than in placebo-treated patients (143.3 +/- 22.8 versus 36.1 +/- 14.3 fmol/mg). The mean fibroid PR and the mean myometrial ER and PR content were not significantly different between treatment groups. Clinically, the significant increase in fibroid ER may be an explanation for the rapid regrowth of fibroids observed after the cessation of GnRH-a therapy.

Antineoplastic Agents↗

The secretion of insulin-like growth factors I and II by explant cultures of fibroids and myometrium from women treated with a gonadotropin-releasing hormone agonist.

The gonadotropin-releasing hormone agonist (GnRH-a) leuprolide acetate depot was used as a biologic probe to investigate the possible roles of insulin-like growth factors (IGFs) I and II in fibroid growth. The secretion of IGF-I and IGF-II by explant cultures of fibroids and myometria from women treated with a GnRH-a was compared with that of tissue obtained from placebo-treated controls. Patients were randomized to receive either leuprolide 3.75 mg every 28 days (N = 9) or placebo injections (N = 8) before myomectomy. Fresh tissue was diced into 2-mm3 explants and cultures were established in serum-free media. The media were assayed for IGF-I, IGF-II, and total protein. Patients treated with GnRH-a demonstrated a 34% reduction in uterine volume, whereas placebo-treated patients exhibited no change. The secretion of IGF-I and IGF-II by fibroid explants obtained from women treated with the GnRH-a was significantly less than that in tissue obtained from placebo-treated controls (P less than .01 and P less than or equal to .05, respectively). Similarly, the secretion of IGF-I and IGF-II by myometrial explants was significantly less in tissue obtained from women treated with GnRH-a (P less than .0001 for both IGF-I and IGF-II). Protein secretion by fibroid tissue obtained from women treated with GnRH-a was not significantly different when compared with tissue from placebo-treated controls. In conclusion, fibroids and myometria from women pretreated with the GnRH-a secreted significantly less IGF-I and IGF-II than did tissue obtained from placebo-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Nicotine and cotinine inhibit rat testis androgen biosynthesis in vitro.

The effects of nicotine and cotinine, the major metabolite of nicotine, on testosterone production in rat testis were investigated. Rat Leydig cells were isolated and incubated with nicotine and cotinine. Nicotine produced a dose dependent increase in progesterone levels and a dose-dependent decrease in androstenedione and testosterone concentrations. Cotinine produced a dose-dependent increase in progesterone and androstenedione and a dose-dependent decrease in testosterone levels. The effects of nicotine and cotinine on rat testis mitochondrial cholesterol side chain cleavage enzyme and microsomal 3 beta-hydroxysteroid dehydrogenase-isomerase, 17 alpha-hydroxylase, 17,20-lyase and 17-ketosteroid reductase were examined. Nicotine competitively inhibited 17 alpha-hydroxylase (apparent Ki = 30 microM) and 17,20-lyase (apparent Ki = 18 microM). Cotinine competitively inhibited 17-ketosteroid reductase (apparent Ki = 46 microM). The addition of nicotine to preparations of rat testis microsomes yielded a Type II cytochrome P-450 binding spectrum. We conclude that nicotine and cotinine competitively inhibit multiple steps in testosterone biosynthesis.

Androgens↗

A rapid DNA probe test for detecting human papilloma virus types 6/11 and 16 in biopsy specimens.

A simple, rapid and sensitive non-radioactive in situ hybridization assay for human papillomavirus (HPV) has been developed and used to detect HPV 6/11 and HPV16 DNA in ano-genital biopsy specimens. A comparative study to determine the sensitivity and the specificity of this assay relative to Southern blot hybridization assays was performed using one hundred biopsy specimens. The sensitivity of the in situ hybridization assay was 88% for HPV type 6/11 and 89% for HPV type 16. The specificity of the test was 99% for both virus types. In addition to its high sensitivity and specificity, this in situ hybridization assay for HPV uses a non-radioactive detection system. The assay is faster and easier to perform than the Southern blot method. Also, in situ hybridization assays permit the simultaneous evaluation of the histology, as well as the DNA content of biopsy tissues because they do not result in the destruction of tissue or cell morphology. This prototype HPV DNA assay was developed using DNA probes for HPV 6/11 and HPV 16 DNA in anogenital biopsy specimens. However, the protocol developed in these studies can easily be extended to include the use of probes for detecting other HPV types in a variety of tissues.

Anal Canal↗

A randomized, placebo-controlled, double-blind study evaluating the efficacy of leuprolide acetate depot in the treatment of uterine leiomyomata.

Thirty-eight premenopausal women with uterine leiomyomata were enrolled in a randomized, double-blind, placebo-controlled study evaluating the efficacy of depot leuprolide acetate (LA), a gonadotropin-releasing hormone agonist, in decreasing uterine volume. Eighteen women received intramuscular (IM) depot LA 3.75 mg every 4 weeks for 24 weeks (group A); 20 women received IM placebo with the same injection schedule (group B). Group A patients had a mean reduction in pretreatment uterine volume from 505 +/- 93 cu cm (mean +/- standard error of the mean) to 305 +/- 57 cu cm after 12 weeks (P less than 0.05 versus pretreatment) and 307 +/- 57 cu cm after 24 weeks of therapy (P less than 0.05 versus therapy (P less than 0.05 versus pretreatment). At 3 months after cessation of therapy, the mean uterine volume in group A had increased to 446 +/- 92 cu cm (P less than 0.05 versus week 24). Group B patients had no significant change in uterine volume over the 24-week treatment period. These results suggest that depot LA therapy may significantly decrease uterine volume in patients with leiomyomata, but that regrowth of uterine size occurs shortly after cessation of therapy.

Adult↗

Treatment of leiomyomata uteri with short-term leuprolide followed by leuprolide plus estrogen-progestin hormone replacement therapy for 2 years: a pilot study.

Five premenopausal women with leiomyomata uteri were treated with leuprolide for 3 months and demonstrated a reduction in mean uterine volume of 49%. Cyclic conjugated equine estrogens and MPA were added to leuprolide therapy during the ensuing 24 months, with no significant changes in mean uterine volume or peripheral bone density.

Bone and Bones↗

Cotinine and nicotine inhibit human fetal adrenal 11 beta-hydroxylase.

The effects of nicotine and cotinine on fetal adrenal 11 beta- and 21-hydroxylase were examined using enzymatic and spectral techniques. The addition of nicotine or cotinine to preparations of adrenal mitochondria yielded a type II cytochrome P-450 binding spectrum. The apparent spectral dissociation constants (Ks) for nicotine and cotinine binding to mitochondrial cytochrome P-450 were 20 and 19 microM, respectively. The addition of nicotine to preparations of adrenal microsomes yielded a type II cytochrome P-450 binding spectrum, with an apparent Ks of 70 microM. Adrenal mitochondrial 11 beta-hydroxylase was assayed by measuring the conversion of deoxycorticosterone to corticosterone. Nicotine and cotinine competitively inhibited 11 beta-hydroxylase, with apparent Michaelis-Menten inhibition constants (Ki) of 9.9 and 9.0 microM, respectively. Nicotine competitively inhibited microsomal 21-hydroxylase, with an apparent Ki of 110 microM. Cotinine, in concentrations as high as 1 mM, did not inhibit 21-hydroxylase. These results suggest that nicotine and cotinine inhibit 11 beta-hydroxylase by binding to the heme iron of the cytochrome P-450 component of this enzyme system. Inhibition of 11 beta-hydroxylase could contribute to the altered pattern of steroidogenesis observed in smokers.

Adrenal Glands↗

A randomized, placebo-controlled, double-blind study evaluating leuprolide acetate depot treatment before myomectomy.

Eighteen premenopausal women with symptomatic leiomyomata uteri were enrolled in a stratified, randomized, double-blind, placebo-controlled study evaluating the efficacy of leuprolide acetate (LA) depot treatment before myomectomy. Stratification was based on pretreatment uterine volume (less than 600 cm3 versus greater than or equal to 600 cm3). Nine women received intramuscular (IM) depot LA 3.75 mg every 4 weeks for 12 weeks (group A); nine women received IM placebo with the same injection schedule (group B). All women underwent myomectomy within 4 weeks of their last injection. Mean total intraoperative blood loss was 213 +/- 44 mL (mean +/- standard error of the mean [SEM]) in group A and 302 +/- 43 mL in group B. When data from patients with large uteri (pretreatment uterine volumes of 600 cm3 or greater) were analyzed, mean total blood loss was 189 +/- 44 mL in group A and 390 +/- 20 mL in group B. These data suggest that leuprolide depot treatment before myomectomy may decrease intraoperative blood loss in women with large leiomyomata uteri.

Delayed-Action Preparations↗

A randomized, double-blind trial of a gonadotropin releasing-hormone agonist (leuprolide) with or without medroxyprogesterone acetate in the treatment of leiomyomata uteri.

A randomized, double-blind study was performed on 16 women to compare the efficacy of daily subcutaneous (SC) injections of leuprolide acetate (LA; TAP Pharmaceuticals, North Chicago, IL) plus oral placebo tablets (group A, n = 7) with SC LA plus oral medroxyprogesterone acetate (The Upjohn Company, Kalamazoo, MI; group B, n = 9) in the treatment of leiomyomata uteri. Patients in group A had a significant reduction in uterine size from a pretreatment volume of 601 +/- 62 cm3 (mean +/- standard error) to a mean uterine volume of 294 +/- 46 cm3 at 24 weeks of therapy (P less than 0.01). Group B patients had a reduction in uterine volume from 811 +/- 174 cm3 to 688 +/- 154 cm3, which was not statistically significant. However, only one patient in group B experienced hot flashes, whereas six patients in group A had this symptom (P less than 0.01). Both groups demonstrated significant increases in mean hemoglobin concentrations, hematocrits, and serum iron levels at 24 weeks of therapy compared with pretreatment levels.

Adult↗

Did Princess Charlotte die of pulmonary embolism?

The cause of death of the Princess Charlotte of Wales in 1817 has been attributed to postpartum haemorrhage. Although an autopsy was performed, pulmonary embolism was not diagnosed because this condition was not recognized until 1846, but the clinical description of her last hours clearly points to pulmonary embolization as the most likely cause of death.

Famous Persons↗

Serum steroid hormone profiles in postmenopausal smokers and nonsmokers.

Morning serum steroid levels were determined in postmenopausal chronic smokers and nonsmokers. Postmenopausal smokers (n = 9) had significantly elevated levels of cortisol, progesterone (P), 17-hydroxyprogesterone (17-OHP), androstenedione, and testosterone compared with nonsmokers (n = 16). The increases were most significant for cortisol (P less than 0.001) and 17-OHP (P less than 0.0005). Estrone, estradiol, dihydrotestosterone, and dehydroepiandrosterone sulfate did not differ between the groups. P to estrogen ratios tended to be higher in the smoking population. The significantly elevated P levels observed in the group of postmenopausal smokers may explain, in part, the epidemiologic finding that women smokers have a decreased incidence of endometrial carcinoma. In addition, the hypercortisolism associated with smoking may increase the risk of osteoporosis.

17-alpha-Hydroxyprogesterone↗

Treatment of leiomyomata with intranasal or subcutaneous leuprolide, a gonadotropin-releasing hormone agonist.

Fourteen premenopausal women with uterine leiomyomata were randomized to receive a gonadotropin-releasing hormone agonist (GnRH-a), leuprolide, either by daily subcutaneous (SC) injection (500 micrograms/day) or by intranasal (IN) spray (1600 micrograms/day) for 24 weeks. In the SC group, a significant reduction in uterine volume occurred from a pretreatment volume of 368 +/- 60 (mean +/- standard error of the mean [SEM]) cm3 to 202 +/- 61 cm3 at 12 weeks of therapy (P less than 0.01) and to 172 +/- 49 cm3 at 24 weeks of therapy (P less than 0.005). In the IN group, no significant reduction in uterine volume occurred. In addition, there was a significant negative correlation between the serum estradiol concentration during treatment and the percent decrease in uterine volume (r = -0.55, P less than 0.05). Four months after completing therapy, uterine volume increased to 296 +/- 104 cm3 in the SC group, which was not significantly different from pretreatment volume. These findings suggest that reduction in uterine volume depends on the degree of hypoestrogenism induced and that uterine volume increases soon after cessation of GnRH-a therapy.

Administration, Intranasal↗

Endocervical curettage as a routine part of colposcopic examinations for abnormal cervical cytology.

Two hundred seven consecutive patients with adequate colposcopy and routine endocervical curettage (ECC) were evaluated for abnormal cervical cytology. A positive ECC was found in 31 patients (15.0%). In patients with grade III cervical intraepithelial neoplasia (CIN), ECC was positive 260% more often than in patients with CIN 1 and 2 (P less than .005). The ECC was the only evidence of dysplasia in three instances. The data suggest that routine ECC should be an integral part of the colposcopic examination of patients with abnormal cytology.

Biopsy↗

Ceftriaxone or cefazolin prophylaxis for the prevention of infection after vaginal hysterectomy.

A prospective, double-blind, perioperative prophylactic antibiotic study was performed in 127 women undergoing vaginal hysterectomy. Patients were randomly given a preoperative 1 g dose of ceftriaxone and then placebo 8 and 16 hours later or three 1 g doses of cefazolin over 16 hours. At surgery, blood samples were collected from 81 women and vaginal mucosa samples, from 49 women. Respective antibiotic concentrations were determined by high-pressure liquid chromatography. During the 10 months of this study, 64 patients received ceftriaxone and 63 received cefazolin. Clinical and surgical profiles of the two groups were similar, and the incidence of postoperative pelvic infection was identical, being 1.6 percent. The mean concentration of ceftriaxone was significantly higher than that of cefazolin in serum (p less than 0.001) and vaginal mucosa (p less than 0.05). A single dose of ceftriaxone before surgery was as effective in preventing major pelvic infection and urinary tract infection as were three perioperative doses of cefazolin given over 16 hours. The safety and tolerance of the two regimens were equivalent.

Adult↗