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Biomedical subjects

M E Toaff

Publications and source records attributed to M E Toaff.

At least 19 recordsLinked to original sources

Value of sonohysterography in the diagnosis and management of abnormal uterine bleeding.

PURPOSE: To assess the value of sonohysterography in the diagnosis and management of abnormal uterine bleeding. MATERIALS AND METHODS: Sonohysterography was performed in 28 women (aged 29-55 years) in whom transvaginal sonography (TVS) suggested an abnormal endometrial echo (n = 14) or fibroids (n = 14). Its effect on diagnosis and treatment was studied. RESULTS: In the patients with an abnormal endometrial echo, sonohysterography depicted endometrial polyps (n = 9), intracavitary fibroids (n = 3), placental polyp (n = 1), and a normal cavity (n = 1). Hysteroscopic resection resolved the bleeding in 11 of 14 patients; surgery was obviated in one. In the group with fibroids, sonohysterography depicted small submucous fibroids amenable to hysteroscopic myomectomy (n = 5), a small mural fibroid with a normal cavity, which obviated surgical intervention (n = 4), and endometrial polyps, which altered the treatment plan (n = 1). Sonohysterography suggested the need for an abdominal myomectomy (n = 4) and alerted the surgeon to explore the uterine cavity in three patients. CONCLUSION: By helping elucidate the cause of bleeding, sonohysterography assisted in determining the therapeutic approach and often reduced the level of surgical intervention or obviated it altogether.

Adult↗

Controlled ovarian hyperstimulation and transvaginal intratubal insemination as an alternative to gamete intrafallopian transfer.

OBJECTIVE: To evaluate the efficacy of controlled ovarian hyperstimulation (COH) followed by intratubal insemination in the treatment of infertility. DESIGN: Retrospective analysis of 179 intratubal insemination trials in 78 women over a 48-month period. SETTING: Reproductive endocrinology practice. PATIENTS: Seventy-eight women, 26 to 44 years old (34 +/- 4.3 years; mean +/- SD), classified into subgroups according to diagnosis and age (< 40 or > or = 40 years). INTERVENTIONS: Patients underwent COH and intratubal insemination. MAIN OUTCOME MEASURES: The rates of pregnancy, delivery, spontaneous abortion, ectopic and multiple gestation, and complications were studied and analyzed statistically. RESULTS: Overall, there were 36 pregnancies (20.1% of 179 trials), 29 deliveries (16.2%), 5 of 36 first trimester abortions (13.9%), 2 of 36 ectopic pregnancies (5.6%), and 4 twin gestations. There were no serious complications. In 43 women < 40 years without male factor the first trial resulted in 15 pregnancies (34.9%); in 27 women < 40 years with male factor the first trial resulted in 4 pregnancies (14.8%). Male factor reduced significantly the probability of conception. In 19 women < 40 years of age with either ovarian dysfunction or infertility of unknown cause, the first trial resulted in 9 pregnancies (47.4%), which was significantly better than the 10 pregnancies achieved in the first trial in the remaining 51 women < 40 years of age. Peak serum E2 levels and number of mature follicles had a significant effect on pregnancy rates. CONCLUSIONS: Intratubal insemination yielded pregnancy rates comparable to those published for GIFT at reduced cost and with fewer complications.

Adult↗

Hysterosalpingography before and after myomectomy: clinical value and imaging findings.

OBJECTIVE: Myomectomy is being performed increasingly for the treatment of menorrhagia and infertility. The purpose of this study was to describe the findings at hysterosalpingography before and after myomectomy and to correlate the findings with the operative technique and observations at surgery. This study also examined the value of hysterosalpingography in planning surgery, as well as in detecting postoperative complications and residual fibroids. MATERIALS AND METHODS: The study group comprised 32 patients who were consecutively referred for hysterosalpingography after myomectomy. The indications for myomectomy were infertility in all cases, associated with menorrhagia in 20, pelvic pain in 15, and urinary frequency in eight. Eighteen of the 32 patients also had hysterosalpingography before surgery. The hysterosalpingographic findings were reviewed without knowledge of the clinical findings and then correlated with surgical and pathologic findings. RESULTS: Preoperative hysterosalpingograms showed enlargement and/or distortion of the uterine cavity in 13 of 14 patients who had submucous fibroids or mural fibroids with a submucous component (mural/submucous fibroid). Cornual asymmetry was seen in seven of 18 patients, the result of an adjacent fibroid deforming one bilaterally in another two. In all four patients, tubal patency was shown after myomectomy. Intracavitary filling defects consistent with submucous or mural/submucous fibroids were found in 12 of 18 patients. After myomectomy, these defects resolved in eight cases; in the remaining four, persistent filling defects suggested residual submucous enlargement of the uterine cavity in only two of 32 patients; in both, residual mural and/or submucous fibroids were shown on sonography after surgery. Major distortion of the cavity after surgery was found in four patients; it was caused by filling defects consistent with residual submucous fibroids in two and by major synechiae in two. Diverticula at the site of resection of submucous fibroids were found in six patients. Major synechiae were found in two patients, resulting in unilateral or bilateral tubal occlusion. CONCLUSION: Hysterosalpingography before myomectomy can assist the surgeon in planning the surgical approach by showing the presence, size, and location of submucous fibroids and concomitant tubal disease. Hysterosalpingography after myomectomy shows residual fibroids and complications of surgery, such as synechiae and diverticula, that may affect further treatment.

Adult↗

Imaging of uterine leiomyomas.

Advances in the medical and surgical treatment of uterine leiomyomas have stimulated interest in the imaging of these common tumors. The purpose of this essay is to illustrate the appearance of leiomyomas on images obtained with various techniques. The advantages of each technique in particular clinical circumstances are discussed.

Female↗

Communicating septate uterus with double cervix: a rare malformation.

The class of uterine malformations known as communicating uteri is characterized by two separate uterocervical cavities connected by an isthmic communication. Nine types have been described. We report the second proven case of a septate communicating uterus with double cervix. Investigation of secondary infertility in a woman with a history of second-trimester spontaneous abortion revealed two cervices on a speculum examination. A work-up for uterine anomaly began with endovaginal sonography, which demonstrated a normal fundal contour. A septum symmetrically dividing the endometrial cavity and two cervical canals were seen. The separated endometrial echoes converged at the isthmus, indicating a communicating uterus. Hysterosalpingography confirmed the diagnosis; injection of each cervix resulted in opacification of both hemicavities via the isthmic defect. Laparoscopy confirmed the normal fundal contour. It is believed that the etiology of this malformation involves failure of fusion of the distal müllerian ducts and arrested septal resorption above the isthmus.

Adult↗

Diagnostic imaging in puerperal febrile morbidity.

This retrospective study was conducted to assess the value of imaging in patients with refractory puerperal febrile morbidity. During a 36-month period, 31 patients were referred for ultrasound and/or computed tomography or magnetic resonance imaging because of postpartum fever unresponsive to broad-spectrum antibiotic therapy of at least 72 hours' duration. Hematomas were identified in 11 women. Abscesses were diagnosed in seven patients, ovarian venous thrombosis in two, vesicouterine fistula in one, small-bowel obstruction in one, and a subcutaneous seroma in one. Twenty-one women had endomyometritis, 13 of whom also had other extrauterine abnormalities (abscess in six, hematoma in four, and ovarian venous thrombosis, vesicouterine fistula, and small-bowel obstruction in one each). Retained placental tissue was found in two women with endomyometritis. Only two subjects had negative imaging studies. In most patients, imaging led to definitive diagnosis and specific therapeutic measures resulting in resolution of the febrile morbidity. Our experience suggests that these imaging techniques may be helpful in evaluating puerperal fever.

Abdomen↗

Leiomyomas in pregnancy: sonographic study.

With ultrasound monitoring, analysis of the behavior of uterine leiomyomas (fibroids) and their impact on the course of pregnancy was undertaken in a group of 113 patients. Fibroid size changes were analyzed on the basis of trimesters. In the second trimester, smaller fibroids increased in size, whereas larger fibroids decreased in size. In the third trimester, a decrease in size was documented regardless of initial size. The most common patterns of echotexture were hypoechoic, heterogeneous, and echogenic rim. The development of a heterogeneous pattern or anechoic/cystic spaces on a follow-up study was accompanied in seven of ten patients by severe abdominal pain, compared with 12 cases of abdominal pain in 103 patients without such echotexture changes. Although the number of patients was small, the development of these patterns apparently indicates significant degeneration of the fibroid. Fibroids located in the lower uterine segment were accompanied by a higher frequency of cesarean section and retained placenta. Fibroids located in the uterine corpus were more frequently associated with early abortions. Multiple fibroids were accompanied by a higher frequency of malpresentation and premature contractions compared with cases with one or two fibroids.

Adult↗

Mechanisms subserving the trophic actions of insulin on ovarian cells. In vitro studies using swine granulosa cells.

Direct actions of insulin on gonadal tissues have been difficult to demonstrate in vivo. We have developed an in vitro system in which swine ovarian cells remain highly responsive to trophic actions of insulin. Purified porcine insulin significantly augmented the biosynthesis and secretion of progesterone by cultured granulosa cells. These stimulatory actions of insulin were dose- and time-dependent and saturable. Under serum-restricted conditions, insulin also significantly amplified the capacity of estradiol and 8-bromo cyclic AMP to stimulate progesterone production. Inhibitors of protein and RNA synthesis (cycloheximide, actinomycin D, and alpha-amanatin) inhibited insulin action. The stimulation of progesterone production by insulin was attributable to increased biosynthesis of pregnenolone, rather than diminished catabolism of progesterone to its principal metabolite, 20alpha-hydroxypregn-4-en-3-one. Insulin also enhanced progesterone production in the presence of a soluble sterol substrate, 5-cholesten-3beta,25-diol, which readily gains access to the mitochondrial cholesterol side-chain cleavage system. Moreover, exposure of granulosa cells to insulin produced a three- to sevenfold increase in mitochondrial content of cytochrome P-450 measured by difference spectroscopy, with a corresponding increase in mitochondrial cholesterol side-chain cleavage activity. The capacity of insulin to facilitate progesterone biosynthesis by ovarian cells was mimicked by the insulinlike somatomedin, multiplication stimulating activity, but not by epidermal growth factor, fibroblast growth factor, or porcine relaxin. Insulin's augmentation of progesterone production reflected a selective action on progestin biosynthesis, since insulin significantly suppressed estrogen biosynthesis by granulosa cells.Thus, our investigations indicate that insulin acts on ovarian cells selectively to stimulate pregnenolone (but not estrogen) biosynthesis. The actions of insulin are exerted by processes that require protein and RNA synthesis, and by mechanisms that augment mitochondrial cytochrome P-450 content and facilitate the utilization of cholesterol in the side-chain cleavage reaction. The striking mimicry of insulin effect by multiplication stimulating activity suggests that insulin action may be mediated through somatomedin receptors. Moreover, in view of the high concentrations of somatomedin in ovarian follicles in vivo, our in vitro observations suggest that specific trophic actions of insulin or insulinlike growth factors are likely to significantly regulate the differentiated function of the Graafian follicle in vivo.

Animals↗

Regulation of cytochrome P-450scc in immature porcine granulosa cells by FSH and estradiol.

FSH, estradiol, or a combination of FSH and estradiol enhanced secretion of progesterone by primary cultures of immature porcine granulosa cells; they also increased the mitochondrial content of cytochrome P-450 and mitochondrial cholesterol side-chain cleavage activity. FSH or estradiol alone increased mitochondrial cytochrome P-450 levels and cholesterol side-chain cleavage activity to a similar extent. The combination of FSH and estradiol further increased cytochrome P-450 and side-chain cleavage activity. Our results demonstrate that FSH, estrogen and the combination of the hormones stimulate progestin synthesis by granulosa cells, at least in part, by increasing cholesterol side-chain cleavage enzyme levels. These observations suggest a dual hormonal regulation of the enzyme catalyzing the rate-limiting step in the biosynthetic pathway of steroid hormones.

Animals↗

Metabolism of 25-hydroxycholesterol by rat luteal mitochondria and dispersed cells.

The metabolism of 25-hydroxycholesterol (25-OH-cholesterol) to progestins by mitochondria and dispersed cells prepared from ovaries of PMSG-hCG-primed rats was studied. Mitochondria converted [3H]25-OH-cholesterol into [3H]pregnenolone and [3H]progesterone. Unlabeled 25-OH-cholesterol also stimulated mitochondrial steroidogenesis in a dose-dependent, saturable fashion. A direct relationship between rates of steroid synthesis in the presence of 25-OH-cholesterol and mitochondrial cytochrome P-450 levels was found. Although steroid production and cytochrome P-450 content per milligram protein were higher in mitochrondia prepared from ovaries removed on day 8 post hCG than on either day 1 or day 14, steroid production per nanomole cytochrome P-450 was similar. Treatment of rats with hCG 1 h before killing significantly increased mitrochondrial steroid synthesis from endogenous substrate but had no effect on metabolism of 25-OH-cholesterol. Dispersed cells increased progestin production by 6-fold when incubated with 25-OH-cholesterol. The effects of 25-OH-cholesterol were dose dependent and saturable. While both LH and (Bu)2cAMP stimulated progestin synthesis from endogenous substrate, secretion of progestins with these agents reached levels only 60% of those observed in the presence of 25-OH-cholesterol. Neither LH nor (Bu)2cAMP altered the metabolism of the dydroxysterol by the cells nor did cycloheximide, which substantially inhibited progestin secretion in the absence of the hydroxysterol. However, animoglutethimide did block the stimulation of steroidogenesis by 25-OH-cholesterol. We conclude that 25-OH-cholesterol is an effective steroidogenic substrate for rat luteal tissue. With its use, information regarding the maximal capacity of luteal tissue to produce progestins in vitro can be obtained.

Aminoglutethimide↗

Regulation of ovarian cholesterol metabolism: control of 3-hydroxy-3-methylglutaryl coenzyme A reductase and acyl coenzyme A:cholesterol acyltransferase.

Activities of enzymes involved in cholesterol metabolism were measured in ovaries of PMS-hCG-primed immature rats. Microsomal 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme in sterol synthesis, was low during the period of maximal steroid production and cholesteryl ester storage. Acyl CoA:cholesterol acyltransferase (ACAT), the microsomal enzyme catalyzing sterol esterification and cytosolic cholesteryl ester hydrolase and mitochondrial cholesterol side chain cleavage activities, paralleled storage of sterol esters and levels of plasma progesterone, being highest on day 7 post hCG. Further experiments demonstrated that HMG-CoA reductase and ACAT are regulated by different mechanisms than the sterol esterase and cholesterol side chain cleavage system. When blood sterol levels were lowered by 4-aminopyrazolo (3,4-d)pyrimidine, plasma progestin concentrations fell and ovaries failed to accumulate sterol esters. HMG-CoA reductase increased more than 10-fold as a result of this treatment, while ACAT was 15% of that measured in controls. In contrast, cholesteryl esterase and the cholesterol side chain cleavage system were not affected. Intravenous infusion of human lipoproteins reversed the effects of 4-aminopyrazolo (3,4-d)pyrimidine. Raising blood levels up to 6-fold with either cholesterol-supplemented diets or intravenous injections of rat lipoproteins had no effect upon ovarian sterol metabolism, suggesting that the process by which blood cholesterol is utilized is saturated at normal blood sterol levels. Intravenous injection of LH on day 7 post hCG increased HMG-CoA reductase and decreased ACAT activity in addition to depleting cholesteryl esters. Prior treatment of rats with aminoglutethimide prevented the effects of LH on both HMG-CoA reductase and ACAT, indicating that changes in these enzymes were a consequence of the steroidogenic stimulus imposed by LH. Treatment with aminoglutethimide alone on day 7 post hCG did not further depress the already low HMG-CoA reductase activity, but ACAT and cholesterol ester storage were stimulated while sterol esterase activity was not altered. Aminoglutethimide also produced elevated ACAT activity and sterol ester storage in animals treated on day 2 post hCG, a time when there is normally little sterol ester accumulation. We conclude that HMG-CoA reductase and ACAT are regulated, in a reciprocal fashion, by ovarian cholesterol balance. When sufficient cholesterol is available, HMG-CoA reductase is suppressed and ACAT increases to facilitate esterification of sterol in excess of cell needs. When exogenous sterol supplies cannot meet ovarian demands, HMG-CoA reductase rises, and there is a concomitant decline in ACAT. Thus, gonadotropic control over these enzymes may be exerted, in part, through modulation of the supply of cholesterol to the ovary and/or through regulation of the rate of sterol utilization for hormone synthesis.

Acyltransferases↗

Presence of a low molecular weight inhibitor of succinate-supported cholesterol side chain cleavage in rat ovaries.

1. Low molecular weight fractions (mol. wt. 3500-10 000) prepared from cytosols of luteinized rat ovaries inhibited succinate-supported cholesterol side chain cleavage by intact ovarian mitochondria utilizing endogenous or exogenous sterol as substrate. 2. The low molecular weight fractions inhibited steroid secretion by collagenase-dispersed ovarian cells stimulated with lutropin or dibutyryl cyclic AMP. 3. Steroidogenesis by intact mitochondria incubated with NADPH was enhanced by the low molecular weight ovarian fraction, but cholesterol side chain cleavage carried out by sonicated mitochondria incubated with NADPH was unaffected. 4. Succinate-supported mitochondrial respiration was stimulated by the low molecular weight factor, apparently by uncoupling of oxidative phosphorylation. The uncoupling seems to be the mechanism by which steroid synthesis is inhibited. 5. The low molecular weight factor was heat-labile and not extracted by activated charcoal. Similar heat-labile material capable of inhibiting succinate-supported mitochondrial steroid synthesis was not found in low molecular weight fractions prepared from rat kidney, liver, spleen, brain, plasma and bovine corpus luteum. 6. Treatment of rats with cycloheximide 1 h before killing resulted in a reduction of inhibitory activity in ovarian low molecular weight cytosolic fractions. 7. We conclude that ovarian cytosols contain a low molecular weight factor, presumably a protein, which inhibits mitochondrial cholesterol side chain cleavage by uncoupling oxidative phosphorylation. The physiological function of this factor remains to be determined.

17-alpha-Hydroxypregnenolone↗