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Biomedical subjects

A J Friedman

Publications and source records attributed to A J Friedman.

At least 37 records · Page 2Linked to original sources

Extending the use of gonadotropin-releasing hormone agonists: the emerging role of steroidal and nonsteroidal agents.

OBJECTIVE: To review and summarize the state of the art as it relates to the long-term application of GnRH agonists (GnRH-a). DESIGN: A retrospective analysis of the available literature and results and an up-to-date review of a rapidly evolving field. CONCLUSION: Although the precise use of long-term GnRH-a therapy (in conjunction with sex steroid add-back therapy) remains unknown, the information provided strongly supports additional studies in this area to achieve a body of promising preliminary data.

Endometriosis↗

Early diagnosis and treatment of cervical pregnancy in an in vitro fertilization program.

This is a report of three cervical pregnancies, one of which was a heterotopic twin cervical pregnancy that occurred in combination with a single intrauterine pregnancy. Transvaginal ultrasound examination was sufficient to establish the diagnosis in two of three patients, and MRI scanning was conclusive in the third. Early diagnosis lead to intervention before 7 weeks gestation in all cases with no complications. The incidence of cervical pregnancy may be higher in IVF-ET than recognized previously.

Adult↗

Long-term medical therapy for leiomyomata uteri: a prospective, randomized study of leuprolide acetate depot plus either oestrogen-progestin or progestin 'add-back' for 2 years.

Treatment of women with leiomyomata with gonadotrophin-releasing hormone agonists (GnRHa) for > 6 months is not recommended because of concerns regarding adverse sequelae of prolonged hypoestrogenism. It has been postulated that addition of low-dose sex steroids to GnRHa treatment, i.e. 'add-back' therapy, may avert some of these adverse effects (accelerated bone resorption, vasomotor flushes) without altering the efficacy of GnRHa therapy. To evaluate the effects of long-term GnRHa therapy on uterine size, bleeding patterns, bone mass and lipids, 51 pre-menopausal women with leiomyomata were treated with the GnRHa leuprolide acetate depot, 3.75 mg every 4 weeks for 2 years. After 3 months of leuprolide therapy, the women were randomized to receive either low-dose continuous oestropipate, 0.75 mg daily, plus cyclic norethindrone, 0.7 mg on days 1-14 each month (the oestrogen-progestin add-back group) or higher-dose norethindrone, 10 mg daily (the progestin add-back group), for the remaining 21 months. Mean uterine volume decreased by 40% in both treatment groups during the first 3 months on leuprolide treatment. There was no significant change in uterine size following oestrogen-progestin add-back. However, mean uterine volume in the progestin add-back group increased to 87% of pre-treatment size by treatment month 12 and 95% of pre-treatment size by treatment month 24. Mean bone density of the lumbar spine as measured by dual X-ray absorptiometry decreased significantly by 2.6% during the first 3 months in all patients, but did not change significantly following steroid add-back in both treatment groups during the final 21 treatment months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Relative overexpression of collagen type I and collagen type III messenger ribonucleic acids by uterine leiomyomas during the proliferative phase of the menstrual cycle.

Uterine leiomyomas contain abundant quantities of extracellular matrix (ECM). We characterized the localization of three ECM proteins, collagen type I, collagen type III, and fibronectin, in leiomyomas and adjacent normal myometrium. We further examined the expression of messenger ribonucleic acid (mRNA) levels for these proteins from 1) women who were in various stages of the menstrual cycle and 2) multiple leiomyomas from the same patient. Immunohistochemical staining showed that fibronectin was localized primarily around individual smooth muscle cells (SMC). Collagen type I was distributed across the ECM and also in the cytoplasm of SMC. Collagen type III was found primarily in the ECM. Leiomyomas showed more intense staining for collagen types I and III than corresponding normal myometrium. Northern blot and densitometric analysis showed that both collagen type I and III mRNAs were consistently elevated in leiomyomas relative to the adjacent myometrium in patients who were in the proliferative phase of the menstrual cycle (P < 0.02 for both). These differences were not evident in the secretory phase. Fibronectin mRNA levels were quite variable, and there were no significant differences between the two tissues at any stage of the menstrual cycle. We conclude that leiomyomas show increased levels of mRNA for collagen types I and III relative to the normal myometrium. However, this difference is only manifested during the proliferative phase of the menstrual cycle. These findings suggest that leiomyomas may be more sensitive to the hormonal changes that occur during the menstrual cycle than is normal myometrium.

Blotting, Northern↗

A self-programmable in vitro fertilization/gamete intrafallopian transfer patient database management system for MacIntosh computers.

PURPOSE: Our purpose was to develop a data processing system for a large in Vitro Fertilization/Gamete Intrafallopian Transfer (IVF/GIFT) practice which would (1) require minimal data entry time, (2) be easy to operate, (3) be simple to construct (no knowledge of procedural language or programming necessary), and (4) quickly collate and reduce data. RESULTS: A database management system was successfully constructed on an Apple MacIntosh computer which met the above criteria. The key elements of this database were its user-friendly features (MacIntosh-based system), adaptability (user was constantly able to update and revise the program as informational needs changed), and ability to perform complex searches and data analyses imposed by the individual operators. CONCLUSIONS: The software and hardware described in this report were found to be highly effective in meeting the ever-changing administrative and clinical needs of our IVF/GIFT program.

Database Management Systems↗

Should uterine size be an indication for surgical intervention in women with myomas?

The quality assurance guidelines published by the American College of Obstetricians and Gynecologists advocate hysterectomy for women with fibroids once the size of the uterus equals or exceeds that at 12 weeks of gestation, regardless of the presence or absence of significant symptoms. Reasons frequently cited by gynecologists for the necessity for surgical intervention include (1) the inability to examine the ovaries, (2) the possible malignancy of the enlarged pelvic mass, (3) the potential for compromise of adjacent organ function if uterine or myomatous growth continues, (4) the greater risks of future surgical treatment if uterine or myomatous growth continues, (5) the potential for greater fertility after surgery on a smaller uterus, and (6) the possibility of continued uterine or myomatous growth resulting from hormone replacement therapy after menopause. A review of the literature reveals surprisingly scant data supporting each of these indications for surgical intervention. The availability of high-resolution ultrasonography and magnetic resonance imaging allows for expectant management in many cases where the uterus is at least 12 gestational weeks in size. The presence and severity of myoma-related symptoms should be the most important considerations in the individualization of treatment strategies.

Female↗

Adverse effects of leuprolide acetate depot treatment.

One hundred two premenopausal women with uterine myomas were treated with LA depot. All women experienced adverse effects during GnRH-a treatment. The majority experienced symptoms attributed to a rapid and sustained decrease in circulating estrogen concentrations beginning 2 to 7 weeks after initiation of treatment. A smaller percentage of women experienced transient adverse effects due to the initial surge and subsequent rapid decline of gonadal steroids. The mechanism of other adverse effects (e.g., arthralgias) remains unclear. Only 6% of women terminated LA treatment before 12 weeks because of the severity of adverse effects.

Adult↗

Acute urinary retention after gonadotropin-releasing hormone agonist treatment for leiomyomata uteri.

A case of rapid uterine enlargement and subsequent urinary retention occurring 7 days after GnRH-a administration in a 53-year-old premenopausal woman with myomas is presented. Rapid uterine enlargement was presumed to be caused by hyperestrogenism shortly after GnRH-a administration. The patient was treated with an indwelling Foley catheter for 2 weeks until the uterus decreased to near baseline dimensions. The patient's uterus continued to decrease in size during the 12 weeks she received GnRH-a, and she underwent an uneventful total abdominal hysterectomy and bilateral salpingectomy/oophorectomy after donating 2 units of autologous blood. This case illustrates that adverse effects from GnRH-a treatment may be caused by the transient increase in ovarian steroid secretion shortly after drug administration.

Acute Disease↗

Gonadotropin-releasing hormone agonist plus estrogen-progestin "add-back" therapy for endometriosis-related pelvic pain.

OBJECTIVE: To evaluate the safety and efficacy of leuprolide acetate depot (LA, Lupron; TAP Pharmaceuticals, Deerfield, IL) plus daily conjugated equine estrogens (Es, Premarin; Wyeth-Ayerst Laboratories, Philadelphia, PA), and medroxyprogesterone acetate (MPA, Provera; The Upjohn Company, Kalamazoo, MI) "add-back" treatment of endometriosis-associated pelvic pain. DESIGN: Retrospective case series. SETTING: Tertiary care, academic medical center. PATIENTS: Eight patients with moderate to severe pelvic pain and laparoscopically documented endometriosis. INTERVENTION: Leuprolide acetate depot 3.75 mg IM every 4 weeks for 24 months. Oral conjugated equine Es 0.625 mg/d plus MPA 2.5 mg/d were also taken from treatment months 3 through 24. RESULTS: Six women completed the 2-year study. Mean revised endometriosis scores for implants, adhesions, and total values were significantly reduced at the conclusion of treatment from pretreatment scores. Self-reported pelvic pain scores were significantly lower at treatment months 3, 6, 12, 18, 24, and 6 months after therapy than pretreatment scores. Dual X-ray absorptiometry bone density measurements of the lumbar spine did not change significantly during the 24-month treatment period. The proportion of women experiencing hot flushes was significantly reduced after E-progestin add-back treatment from the proportion at treatment month 3. CONCLUSION: Treatment with LA depot plus conjugated equine Es and MPA for 2 years was a safe and effective therapy for women with endometriosis and pelvic pain in this small retrospective study.

Adult↗

Leuprolide acetate depot decreases the number of nucleolar organizer regions in uterine leiomyomata.

Women with symptomatic uterine myomas were randomized to receive LA depot or placebo for 12 weeks before myomectomy. Silver staining nucleolar organizer regions (AgNORs) per nuclei were assessed in the tissue obtained at the time of myomectomy. Myoma tissue from women treated with LA depot before myomectomy had significantly fewer AgNORs per nuclei than myoma tissue obtained from women treated with placebo. Leuprolide acetate depot may reduce the number of proliferating cells in myomas.

Adult↗

Combined oestrogen-progestin treatment of vaginal haemorrhage following gonadotrophin-releasing hormone agonist therapy of uterine myomas.

Three pre-menopausal women with uterine myomas were treated with leuprolide acetate depot and experienced profuse vaginal bleeding 7-11 weeks after initiation of treatment, despite profound oestradiol suppression. In each case, leuprolide therapy was discontinued and the women were treated with combination oral contraceptives and ferrous sulphate. Vaginal bleeding ceased within 24-48 h of oral contraceptive treatment in all women. Haemoglobin concentrations were restored to normal values and all women underwent definitive surgical treatments after 4-6 weeks of oral contraceptive treatment without the need for homologous blood transfusion. The final pathology report revealed focal necrosis of submucous myomas in all cases.

Adult↗

Production of prolactin by smooth muscle cells cultured from human uterine fibroid tumors.

Uterine leiomyomas, which are myometrial smooth muscle tumors, secrete PRL. We investigated the actions of several hormones known to stimulate PRL secretion by the pituitary gland or decidua on PRL secretion by leiomyoma-derived smooth muscle cells (SMC) in monolayer culture. Cultures were verified to be SMC by immunostaining for smooth muscle alpha-action and desmin. Hormone treatments were performed in serum-free medium for 72 h. Medium was harvested every 24 h and assayed for PRL. 17 beta-Estradiol, progesterone, TRH, insulin-like growth factor-I, epidermal growth factor, and the GnRH agonist leuprolide did not affect PRL secretion by these SMC. Insulin caused a significant suppression of PRL secretion by 72 h, and this was accompanied by a 64% increase in total cell protein per well, which represented an increase in cell number. Cells were also plated at various densities to determine the effects of cell number on PRL secretion. The amount of PRL secreted per 1000 cells decreased significantly as cell number per well increased. Northern blot analysis identified PRL mRNA in fresh leiomyoma tissue. PRL mRNA in three independent cultures of SMC was then detected by reverse transcription and the polymerase chain reaction. Hybridization occurred only with the expected band of approximately 423 basepairs in size. We conclude that leiomyomas express PRL mRNA in vivo and that leiomyoma-derived SMC in culture continue to express the PRL mRNA and secrete PRL in the absence of ovarian steroids. PRL secretion by SMC in culture appears to be modulated primarily by changes in cell density.

Base Sequence↗

A prospective, randomized trial of gonadotropin-releasing hormone agonist plus estrogen-progestin or progestin "add-back" regimens for women with leiomyomata uteri.

Treatment of women with myomas with GnRH agonists (GnRH-a) for 3-6 months will result in profound hypoestrogenism, a significant but temporary reduction in uterine volume, and menstrual suppression. Long-term (i.e. > 6 months) treatment with a GnRH-a is not recommended because of accelerated bone resorption and the presence of hypoestrogenic symptoms. In this 2-yr study, women with myomas were treated with GnRH-a plus one of two steroid "add-back" regimens to minimize adverse sequelae of chronic hypoestrogenism. Fifty-one premenopausal women with large, symptomatic uterine myomas all received the GnRH-a, leuprolide acetate depot (LAD), every 4 weeks for 12 weeks at which time the women were randomized to receive LAD plus either an estrogen-progestin or progestin-only add-back regimen for an additional 92 weeks. Efficacy parameters assessed included serial uterine volumes, hemoglobin concentrations, and hematocrits; safety parameters evaluated included serial bone mineral density measurements, lipid profiles, and medication-related symptoms. This report analyzes the first 52 weeks of study data. Mean uterine volume decreased to 64% of pretreatment size at 12 weeks of LAD treatment in both groups. The estrogen-progestin add-back group had no significant regrowth of uterine volume, which was 75% of pretreatment size at treatment week 52; in contrast, the progestin add-back group had a mean uterine volume of 92% of pretreatment size by treatment week 52. Both groups demonstrated significant improvements in mean hemoglobin concentrations and hematocrits. The progestin add-back group had a significant decline in mean high density lipoprotein-cholesterol concentration, which was not seen in the estrogen-progestin add-back group. Finally, after a significant 3% bone loss during the first 12 weeks of treatment, bone mineral density stabilized in both add-back regimen groups. GnRH-a/steroid add-back regimens provide a useful long-term treatment strategy in women with large, symptomatic uterine myomas and may obviate the need for surgical intervention in selected cases. The estrogen-progestin add-back regimen was superior or equal to the progestin add-back regimen in all efficacy and safety parameters assessed.

Adult↗

The concentrations of collagen-associated amino acids are higher in GnRH agonist-treated uterine myomas.

OBJECTIVE: To test the hypothesis that the effects of estrogen reduction on uterine leiomyoma regression are mediated through changes in cell density or the extracellular matrix. METHODS: Uterine myomas were obtained from 20 women who had received randomly either the GnRH agonist leuprolide acetate depot for 3 months or placebo. The biochemical and morphologic characteristics studied included: total protein, DNA, and amino acid concentrations; histologic appearance; collagen content; and nuclear density. RESULTS: The absolute and relative concentrations of hydroxylysine, hydroxyproline, glycine, and proline were significantly greater (P < .05) in uterine myomas from patients pretreated with a GnRH agonist compared with placebo-treated controls. The GnRH agonist was also associated with trends toward increased mean total protein, DNA, and nuclear density, but the differences did not reach statistical significance. CONCLUSIONS: The concentrations of the amino acids contained in collagen were significantly greater in uterine myomas from patients treated with the GnRH agonist compared to myomas from placebo-treated controls. In addition, our observations suggest that the reduction in uterine myoma volume associated with GnRH agonist therapy is associated with alterations in the extracellular matrix.

Amino Acids↗

The effect of operative technique and uterine size on blood loss during myomectomy: a prospective randomized study.

OBJECTIVES: To compare operative blood loss between two accepted blood loss-reducing techniques used during myomectomy and to evaluate the effect of preoperatively determined uterine volume on blood loss. DESIGN: Subjects were stratified by ultrasound-determined uterine volume < 600 cm3 (n = 11) and > or = 600 cm3 (n = 10) and then randomized into treatment groups. The same radiologist, surgeons, and anesthetic induction technique were involved in every case. In the pharmacologic technique, diluted vasopressin (20 U in 20 mL normal saline) was injected into the serosa and/or myometrium overlying the fibroid(s) before the uterine incision(s). In the mechanical technique, a penrose drain tourniquet was passed through defects created in the broad ligaments at the level of the internal os and secured posteriorly, occluding the uterine vessels. In addition, vascular clamps were placed on the infundibulopelvic ligaments, occluding anastomotic blood flow through the ovarian vessels. RESULTS: There was no difference in operative blood loss, operating time, preoperative and intraoperative mean arterial blood pressures, postoperative febrile morbidity, preoperative and postoperative hematocrits, transfusion rates, and length of hospital stay between groups. Blood loss was significantly greater for uteri with ultrasound-determined volumes > or 600 cm3 (627 +/- 175 mL, mean +/- SEM) than for those < 600 cm3 (228 +/- 49 mL). For all subjects, blood lost while operating on the uterus (mean, 379 mL; range, 35 to 1,968 mL) was positively correlated with the total weight of the fibroids resected and with time spent operating on the uterus. Total blood loss (mean, 418 mL; range, 42 to 1,968 mL) was also positively correlated with the time spent operating on the uterus and with total operating time. CONCLUSIONS: There were no demonstrable differences in blood loss, morbidity, or transfusion requirements between subjects undergoing myomectomy using pharmacologic vasoconstriction and mechanical vascular occlusion techniques. Blood loss during myomectomy is primarily incurred while operating on the uterus and is correlated with preoperative uterine size, total weight of fibroids removed, and operating time.

Adult↗

Detecting semen antisperm antibodies in the clinical laboratory.

Although antisperm antibodies are associated with infertility, many hospital laboratories do not test for these antibodies. This study included 520 males who were referred for infertility evaluation. Semen samples from all patients were tested for antisperm antibodies by using the mixed antiglobulin reaction and immunobead binding tests. These results were correlated with the findings of semen analyses, postcoital tests, and sperm penetration assays. Eighty-eight men (16.9%) tested positive for IgG, IgA, or IgM antisperm antibodies. More samples tested positive for IgG antibodies by the mixed antiglobulin reaction than by the immunobead test (n = 71 vs n = 42); 57 samples tested IgA positive. Both methods showed good reproducibility (97.6%). Antibody-positive males had a higher incidence of abnormal semen analyses (92% vs 74%) and other immune-related fertility test results (94.2% vs 38.4%). The presence of antisperm antibodies correlates with other abnormal semen parameters. Testing for these antibodies should be included in an infertility evaluation and could be readily implemented in a clinical laboratory.

Antibodies↗