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Biomedical subjects

Z Blumenfeld

Publications and source records attributed to Z Blumenfeld.

At least 109 records · Page 6Linked to original sources

Partial loss of responsiveness of human fetal pituitary cells to hGHRH after chronic exposure.

Synthetic hGHRH was incubated with dispersed pituitary cells from 14 human fetuses at 14-23 weeks of fetal age. After at least three days following plating the cells on an extracellular matrix in serum-containing medium, 3 h incubation with hGHRH in serum-free medium induced a significant increase in GH secretion into the medium at concentrations of hGHRH of 0.01 nmol/l or higher. After 24 h exposure to 0.5 nmol/l hGHRH, subsequent incubation with 0.5 nmol/l hGHRH for 3 h induced significantly lower GH secretion into the medium compared to the GH secretion by cells exposed previously to medium alone. In contrast, when the subsequent exposure to hGHRH was at 10-fold higher concentrations than the concentration present in the initial exposure, GH secretion into the medium did not significantly decrease compared to previously untreated cells. These results suggest that desensitization (down-regulation) of GHRH receptors on somatotropes may be involved in the mechanism by which prior GHRH exposure inhibits GH secretion in response to subsequent GHRH administration. Such desensitization seems to occur in the human fetus but is incomplete. The desensitization may be overcome by increasing the GHRH concentrations with subsequent exposure, suggesting that cellular GH depletion is not responsible for the decreased responsiveness observed.

Cells, Cultured↗

Use of an agonistic analog of gonadotropin-releasing hormone (nafarelin) to treat leiomyomas: assessment by magnetic resonance imaging.

The purposes of this study were to investigate the effect of a superactive agonistic analog of gonadotropin-releasing hormone, nafarelin, on uterine leiomyomas and to assess the use of magnetic resonance imaging in monitoring uterine and myoma size. Eleven women with uterine leiomyomas were treated with 800 micrograms of nafarelin per day for 6 months. Serum gonadotropin and estradiol concentrations were suppressed during treatment. The mean +/- SEM serum luteinizing hormone level decreased from 11.1 +/- 1.4 to 5.6 +/- 0.42 mlU/ml and follicle-stimulating hormone from 9.5 +/- 0.66 to 7.5 +/- 0.72 mlU/ml by 3 months of treatment (p less than 0.01). The estradiol level decreased from a pretreatment follicular phase mean +/- SEM of 43 +/- 8.3 to 19.8 +/- 3.1 (p less than 0.05) and 14.8 +/- 2.2 pg/ml (p less than 0.01) at 3 and 6 months of treatment, respectively. Mean pretreatment androgen levels (testosterone, androstenedione, and dehydroepiandrosterone sulfate) were low in these women and did not change significantly during treatment. Ten women had magnetic resonance imaging, which provided excellent resolution of individual uterine myomas. As assessed by magnetic resonance imaging, the largest myoma decreased in size in nine of 10 women; the mean decrease was 46% +/- 9%. Uterine volume decreased in all 10 patients; the mean decrease was 57% +/- 7%. In several women myomas reenlarged after discontinuance of nafarelin treatment. Posttreatment myomectomy was carried out in four women; there was minimal blood loss and no surgical complications. These data indicate that suppression of ovarian estrogen production with nafarelin is associated with a decrease in uterine myoma size in many women but that myomas may regrow with reinstitution of ovarian function. Magnetic resonance imaging is an excellent method by which to monitor treatment as changes in the size of the uterus, as well as individual myomas, can be assessed. The optimal use of gonadotropin-releasing hormone analogs may be in perimenopausal women or as presurgical treatment to decrease uterine and myoma size to facilitate myomectomy.

Adult↗

Luteal dysfunction in ovulation induction: the role of repetitive human chorionic gonadotropin supplementation during the luteal phase.

Several studies have indicated that ovulation induction with human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) or clomiphene citrate (CC) is associated with luteal phase defect. To assess the efficiency of luteal support by hCG to an infertile population undergoing ovulation induction, with CC/hCG or hMG/hCG, we have randomly administered 2500 IU hCG intramuscularly on days 3, 6, and 9 after ovulation induction by 10,000 IU of hCG to 74 patients on 265 treatment cycles. As controls served 357 ovulation induction cycles in the same 74 patients. The treatment cycles were randomly alternated with control cycles so that each patient served as her own control. However, the mean +/- standard deviation (SD) midluteal P was 38.1 +/- 10.8 ng/ml in the study group versus 15.7 +/- 10.5 ng/ml in the control group (P less than 0.001). Luteal phase length was 15.4 +/- 1.5 days in the treatment group versus 12.1 +/- 1.7 in the control group (P less than 0.01). In the treatment group, 64.8% of the patients achieved pregnancy (27% pregnancies/treatment cycle) versus 47.3% in the control group (11.5% pregnancies/control cycle) (P less than 0.01). The pregnancy wastage rates (including abortions and "chemical" pregnancies) were 30.6% in the treatment group versus 56% in the control group (P less than 0.01). We conclude that repetitive hCG administration may be an efficient luteal support in infertile patients undergoing ovulation induction.

Adult↗

Gonadotropin-releasing hormone (GnRH) antibodies formation in hypogonadotropic azoospermic men treated with pulsatile GnRH--diagnosis and possible alternative treatment.

Five hypogonadotropic azoospermic men received pulsatile, intravenous gonadotropin-releasing hormone (GnRH) treatment over prolonged period. In three patients, the spouses were successful in achieving five pregnancies, three of which generated five healthy newborns, one ended in a first-trimester abortion, and one is ongoing. In one patient, anti-GnRH antibodies were detected, secondary to initial response. This was associated with deterioration of gonadotropin levels and diminution in testosterone to pretreatment levels. The cross-reactivity of the antibodies with five GnRH agonistic analogs was examined. Possible treatment with pulsatile GnRH analogs in such patients is discussed. In light of the relatively long period of treatment needed to achieve spermatogenesis and fertility in patients with hypogonadotropic azoospermia, monitoring the appearance of GnRH antibodies seems appropriate to assess whether therapy should be concluded. The superiority of intravenous pulsatile GnRH treatment to subcutaneous GnRH treatment or to human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) treatment is discussed.

Adolescent↗

Induction of spermatogenesis and fertility in hypogonadotropic azoospermic men by intravenous pulsatile gonadotropin-releasing hormone (GnRH).

Gonadotropin-releasing hormone (GnRH) has only recently become a helpful tool in the medication of hypogonadotropic hypogonadism (HH). Two azoospermic patients with HH who had previously been treated with hCG/hMG because of delayed puberty and each of whom had fathered a child after previous gonadotropin therapy were referred due to secondary failure of hCG/hMG treatment to induce spermatogenesis and fertility. A pulse study where blood was drawn every 15 minutes for LH, FSH and PRL RIAs was performed in each patient, and afterwards a bolus of i.v. GnRH was injected to assess gonadotropin responsiveness. A portable GnRH pump was connected to each patient so that it administered 5-20 micrograms of GnRH i.v. every 89 minutes. Spermatogenesis was first detected after 42 and 78 days respectively in the 2 treated HH men and 4 1/2 months from the start of treatment their wives became pregnant. No thrombophlebitis or other complications of the i.v. therapy occurred. In the case of the first patient, the semen was washed and concentrated and intra-uterine inseminations were carried out in an attempt to shorten the time needed to achieve fertility. The first pregnancy was successfully terminated at 38 weeks with the delivery of 2 heterozygotic normal male babies. The second pregnancy ended in spontaneous delivery of a healthy female. We conclude that i.v. pulsatile, intermittent GnRH administration is a safe, efficient and highly successful means of treating azoospermic men with HH.

Adolescent↗

Peripartum congestive cardiomyopathy and endocardial fibroelastosis associated with ritodrine treatment. A case report.

Congestive cardiomyopathy from endocardial fibroelastosis occurred in a 24-year-old primigravida with a twin gestation and preeclampsia. The patient was taking ritodrine for premature labor. Cardiovascular evaluation should be performed during the course of ritodrine treatment, and no patient should be discharged if she does not have normal cardiovascular function.

Adult↗

Corticotropin-releasing factor can stimulate gonadotropin secretion by human fetal pituitaries in superfusion.

In previous studies, corticotropin-releasing factor was found to elicit a rise in circulating adrenocorticotropic hormone in human subjects and laboratory animals, but no stimulatory effect of corticotropin-releasing factor on other pituitary hormones was detected. Since stress may be associated with luteinizing hormone changes as well as with those of corticotropin-releasing factor and adrenocorticotropic hormone, we quantified gonadotropin responses to corticotropin-releasing factor and arginine vasopressin in 11 human fetal pituitaries with use of both superfusions and static incubations. Exposure to corticotropin-releasing factor brought about a significant increase in adrenocorticotropic hormone and gonadotropin concentrations in the effluent media by means of the superfusion system. Similar concentrations of corticotropin-releasing factor significantly increased adrenocorticotropic hormone secretion into the medium by dispersed fetal pituitary cells cultured on an extracellular matrix but failed to increase luteinizing hormone and follicle-stimulating hormone secretion. Exposure to 3 mmol/l 8-bromo-cyclic adenosine monophosphate caused an increase in all three peptides, both in superfusion and static incubations. Dose-response studies showed that the effect on gonadotropin secretion occurred at concentrations of 8-bromo-cyclic adenosine monophosphate two orders of magnitude lower than those affecting adrenocorticotropic hormone secretion. The purity of corticotropin-releasing factor and arginine vasopressin used in these studies was confirmed by high-performance liquid chromatography. These in vitro results are consistent with a paracrine effect of corticotropes acting on gonadotropes. The combination of static incubation and superfusion has proved useful in elucidating the effects of different secretagogues on pituitary cells.

8-Bromo Cyclic Adenosine Monophosphate↗

Hypophysiotropic and neuromodulatory regulation of adrenocorticotropin in the human fetal pituitary gland.

Synthetic human corticotropin-releasing factor (hCRF) stimulated ACTH secretion by human fetal pituitaries in superfusion and dispersed human fetal pituitary cells cultured on an extracellular matrix in static incubation from 14 to 23 wk gestational age. The action of hCRF in vitro was potentiated by arginine vasopressin (AVP) at all ages studied. 8-Br-cAMP induced a response similar to hCRF. The AVP effect on ACTH was synergistic with both CRF and 8-Br-cAMP. hCRF-mediated secretion of ACTH was noncompetitively inhibited by 24-h pretreatment, or by 3-h concomitant treatment, with dexamethasone. Neither oxytocin, catecholamines, prostaglandins, nor indomethacin exerted significant effects on ACTH secretion, either alone or in combination with hCRF or AVP during the gestational ages studied. These results support a physiologic role for CRF in the regulation of secretion by corticotropic cells as early as 14 wk gestation, by which time corticotropes and ability to secrete ACTH have been demonstrated.

8-Bromo Cyclic Adenosine Monophosphate↗

Dose-dependent inhibition of pituitary-ovarian function during administration of a gonadotropin-releasing hormone agonistic analog (nafarelin).

To determine if treatment with the GnRH agonistic analog nafarelin could reliably block ovulation while only partially disrupting ovarian estrogen production, three degrees of pituitary-ovarian inhibition were investigated. Thirty-two women with ovulatory menstrual cycles were given 125 micrograms (group (Gp) I), 250 micrograms (Gp II), or 1000 micrograms (Gp III) nafarelin daily by intranasal spray. Twenty-seven women completed 6 months of treatment. Basal serum FSH concentrations decreased (P less than 0.01) in all groups. Suppression of serum LH was dose dependent and significant (P less than 0.01) only in Gps II and III. Pituitary desensitization to nafarelin developed in all groups. Peak LH responses to nafarelin decreased by about 70% (Gps I and II) and 95% (Gp III). Basal serum estradiol levels after 1 month of treatment were approximately 70 pg/ml (Gp I) and 25 pg/ml (Gps II and III). Serum estradiol levels increased acutely in Gps I and II, but not in Gp III, in response to each dose of nafarelin. Thus, average daily estradiol levels in Gp II were higher than those in Gp III. Serum testosterone and androstenedione levels decreased slightly (P less than 0.05; Gp II) or by 50% (P less than 0.01; Gp III) during treatment. The effects of nafarelin on ovulatory function also were dose-dependent. In Gp I there were four ovulations (progesterone, greater than 4 ng/ml) and seven instances of luteinization (progesterone, 2-4 ng/ml) during 73 months of nafarelin administration. In contrast, there were no ovulations during 58 and 44 months in Gps II and III, respectively. After discontinuance of nafarelin, ovulatory menstrual function returned rapidly in all women. In summary, inhibition of pituitary-ovarian function by daily intranasal nafarelin administration is dose dependent. Gonadotroph sensitivity to 125 micrograms is variable, and there is inconsistent inhibition of ovulation. Daily doses of 250 or 1000 micrograms analog reliably inhibit ovulation, but are associated with either moderate (Gp II) or marked (Gp III) reduction of ovarian estradiol secretion. The effects of these reduced levels of circulating estradiol on bone are not known. Further investigation, with dosage adjusted according to individual patient sensitivity, may lead to the development of a clinically acceptable contraceptive which consistently inhibits ovulation while maintaining serum estradiol levels sufficient to prevent osteoporosis.

Administration, Intranasal↗

An improved sperm immobilization test based on multiple exposure photography.

An improved method for objective evaluation of results in the complement dependent sperm immobilization test, with the aid of the multiple exposure photography (MEP) method is described. With this method it is possible to determine the percentage of residual motility of spermatozoa quantitatively after incubation with sera suspected of having immobilizing activity in the presence of complement. Long term storage of information, reexamination of data and comparison of results after various treatment are routinely possible with this method.

Antibodies↗

Effect of acute hypoxia on human fetal heart rate. The significance of increased heart rate variability.

The fetal heart rate response to acute hypoxemia was observed during an accidental drop in oxygen concentration inspired by the mother in labor. There was a marked increase in FHR variability in the early stage of hypoxia and also during the recovery phase. While an increase in fetal heart variability is generally considered to be a normal physiological event, it may also indicate a state of fetal hypoxemia associated with an intact fetal circulation, and should be treated with caution during labor.

Adult↗

Clinical, endocrine and ultrastructural study of XY gonadal dysgenesis. A case report.

About 120 cases of XY gonadal dysgenesis have been reported on. We treated such a patient with bilateral gonadectomy. The gonadal tissue's capacity to respond to hormonal trophic stimulation was assessed. When the gonads were examined ultrastructurally, structures with the morphologic characteristics of stromal ovarian cells, Sertoli's cells and Leydig's cells were found. Because of the potential malignancy of the XY gonads, bilateral gonadectomy and hormonal substitution therapy are recommended for these patients. We prefer to use combined hormone replacement with sequential estrogen and progesterone rather than sequential unopposed estrogen because of the small but increased risk of endometrial hyperplasia and carcinoma after long-standing sequential therapy.

Adolescent↗

Increased alpha-fetoprotein levels in mixed mesodermal tumor of the ovary.

2 Cases of mixed mesodermal tumor of the ovary with elevated peripheral levels of alpha-fetoprotein (alpha-FP) were studied. The morphology of these tumors is presented. The finding of hyaline droplets of alpha-FP is of special interest. The histogenesis of the tumor was reappraised in light of the increased level of the marker.

Aged↗

Changes in lipoproteins and subfractions following oophorectomy and oestrogen replacement in peri-menopausal women.

Serum cholesterol concentrations in lipoprotein fractions and subfractions were determined in 11 peri-menopausal women both before and after bilateral oophorectomy, as well as 60 days after commencement of oral oestradiol replacement therapy. Pre-operatively, all subjects were found to have normal lipid and lipoprotein concentrations. There was a post-operative increase in the total cholesterol level, which was attributed to a raised very-low-density lipoprotein (VLDL) cholesterol. Changes in high-density lipoprotein (HDL) subfractions HDL-2 and HDL-3 were noted but since these were compensatory little difference in total HDL cholesterol was observed. Following oral oestrogen replacement, the cholesterol level decreased as a result of a drop in both VLDL and low-density lipoprotein (LDL) cholesterol. The oestradiol-induced HDL cholesterol increment reflected an increase in the levels of both HDL subfractions.

Castration↗