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Biomedical subjects

S Nader

Publications and source records attributed to S Nader.

At least 37 records · Page 2Linked to original sources
PubMed1992

Endogenous luteinizing hormone surges following administration of human chorionic gonadotropin: further evidence for lack of loop feedback in humans.

The existence of inhibitory short- and ultrashort-loop feedback mechanisms for luteinizing hormone (LH), while documented in animals, has been questioned in humans. Since human chorionic gonadotropin (hCG) binds to LH receptors but can be distinguished from LH in immunoassays, it is possible to identify LH surges in the face of exogenously administered hCG. The present study demonstrates LH surges at midcycle in normal volunteers and in women undergoing controlled ovarian hyperstimulation, given hCG. This provides further evidence for lack of loop feedback control of LH secretion in humans.

Chorionic Gonadotropin↗
PubMed1992

Comparison of Nb2 lymphoma cell bioassay with immunoassay for human prolactin: the role of estrogen.

The Nb2 lymphoma cell bioassay (BA-PRL) is a sensitive measure of serum prolactin under physiologic conditions. Since estrogens prime the lactotroph, prolactin heterogeneity and hence bioassayable prolactin may be influenced. A study was performed to observe the effect on BA-PRL of changing estradiol (E2) concentrations. In 13 normal subjects clomiphene citrate was administered to stimulate ovarian activity and blood samples were obtained before and after stimulation. Estradiol, BA-PRL and immunoassayable prolactin (RIA-PRL) were measured. While there was a substantial increase in E2 post-stimulation (p less than 0.001), there was no significant change in BA-PRL, RIA-PRL or BA/RIA-PRL ratios. Despite the lack of change in the mean BA/RIA-PRL ratio over a wide range of E2 concentrations that include and exceed those normally seen in spontaneous menstrual cycles, it is difficult to drawn conclusions regarding an association between E2 and BA/RIA-PRL ratios as there was no discernible change in the concentration of prolactin (possibly due to the antiestrogenic effect of clomiphene citrate).

Adolescent↗
PubMed1992

The effect of haloperidol on aldosterone secretion.

Haloperidol (0.02 mg/kg, intravenous) did not stimulate aldosterone secretion in six normal controls or in six schizophrenic subjects. This is contrary to our hypothesis, which was based on the finding that peripheral D2 receptor antagonists stimulate aldosterone secretion, including haloperidol in rats and chlorpromazine in man. We speculated that a different dose of haloperidol would stimulate aldosterone in man. As expected, prolactin release was markedly stimulated in both groups of subjects, but no difference was found between groups.

Adult↗
PubMed1992

Kinetics and viral protein specificity of the cytotoxic T lymphocyte response in healthy adults immunized with live attenuated varicella vaccine.

The cytotoxic T lymphocyte (CTL) response was evaluated in adults given live attenuated varicella vaccine, using target cells expressing varicella-zoster virus (VZV) immediate-early protein (IE62) or VZV glycoproteins gpI, gpIV, or gpV to determine viral protein specificity. The frequency of CTL that recognized IE62 was 1:171,000 +/- 46,000 SE in subjects tested 10 days to 8 weeks after the initial vaccine dose; the induction of CTL specific for gpI was equivalent. CTL recognition of VZV proteins was mediated by CD4+ or CD8+ cells. CTL recognition of IE62 and gpIV persisted in vaccinees (tested approximately 4 years later) and was comparable to that in the naturally immune. The mean frequency of CTL specific for gpV was lower (but not significantly) in vaccinees than in naturally immune subjects. Assay of responder cell frequencies showed persistence of equivalent numbers of T lymphocytes that recognized IE62 and gpI in vaccinees and naturally immune subjects. Immunization with this vaccine elicited memory T lymphocyte responses to VZV comparable to those induced by natural infection.

Antibodies, Viral↗
PubMed1991

Polycystic ovary syndrome and the androgen-insulin connection.

The association of hyperandrogenism, insulin resistance, and polycystic ovarian disease is well established. The accompanying hyperinsulinemia results in acanthosis nigricans, an epiphenomenon of this syndrome. The knowledge that states of insulin resistance of diverse causes are associated with ovarian hyperandrogenism makes the argument for insulin-driven ovarian androgen secretion compelling. However, equally compelling evidence suggests that hyperandrogenism may contribute to insulin resistance and hyperinsulinemia. The irreconcilable differences between these two hypotheses have resulted in an array of contradictory studies. In this article a unified concept of polycystic ovary syndrome and its androgen-insulin connection is proposed. The hypothesis incorporates the role of hyperinsulinemia in the androgen excess observed (and vice versa); the key to this connection is the androgen-dependent change in regional body fat distribution and its metabolic consequence. The pathophysiologic features of polycystic ovary syndrome, which has important clinical sequelae, deserve further consideration.

Androgens↗
PubMed1991

Premenstrual syndrome. Tailoring treatment to symptoms.

Despite the interest in premenstrual syndrome (PMS) taken by the media and the public in recent years, some women still do not recognize the cyclic nature of their symptoms. Thus, PMS continues to elude diagnosis. Dr Nader discusses the major categories of symptoms and when they occur, summarizes theories on the cause of PMS, and comments on how well these theories have been substantiated by testing. Choosing agents for treatment on the basis of symptoms to be controlled is also described.

Bromocriptine↗
PubMed1991

Use of the hormonal response to clomiphene citrate as an endocrinological indicator of ovarian ageing.

We compared the gonadotrophin and oestradiol responses to clomiphene citrate (CC) in women aged 18-25 versus 35-40 years. Despite similar baseline hormone concentrations and the attainment of similar concentrations of the E and Z isomers of clomiphene, higher follicle stimulating hormone (FSH) concentrations were observed in the older women, possibly indicative of their ageing ovaries. Furthermore, diminished oestradiol responses occurred in a subgroup of women showing FSH hyper-responsiveness to CC. These preliminary results support the concept that the hormonal response to CC may be an indicator of approaching perimenopause.

Adolescent↗
PubMed1990

Study of the pharmacokinetics of human chorionic gonadotropin and its relation to ovulation.

The pharmacokinetics of human chorionic gonadotropin (hCG) was studied in 15 normal volunteers and 15 patients undergoing in vitro fertilization (IVF). Each subject received 6000 IU hCG, intramuscularly (im), at midcycle, and serum was assayed for hCG frequently for 16 hr. All 30 subjects achieved hCG concentrations greater than or equal to 10 IU/liter within 2 hr and 19 (63%) did so within 1 hr of injection. The time taken to attain concentrations of greater than or equal to 20 and greater than or equal to 40 IU/liter correlated positively with the subjects' weight and/or surface area, but the correlation was not strong. Eleven of the 15 IVF patients had oocytes retrieved 34-35 + hr post hCG. Three of the 11 showed evidence of prior "undetected ovulation" at the time of surgery (definite in one, presumed in two). Taking into consideration the pharmacokinetics of hCG and other factors that could lead to undetected ovulation, the authors conclude that (1) hCG is rapidly absorbed in the majority of subjects following im injection, (2) ovulation may occur earlier than 36 hr following hCG in some individuals, and (3) implementation of a shorter (than 35 hr) hCG-to-oocyte retrieval interval would be advised if undetected ovulation is to be avoided.

Adult↗
PubMed1990

Prolactin response to thyrotropin-releasing hormone in normoprolactinemic patients with ovulatory dysfunction and its use for selection of candidates for bromocriptine therapy.

It has been suggested in the past that some normoprolactinemic patients with amenorrhea or infertility respond to treatment with bromocriptine. However, the beneficial effect of this therapy in normoprolactinemic women remains controversial. Some authors have suggested that the responders suffer with "reactive" hyperprolactinemia and that this may be detected with thyrotropin releasing hormone (TRH) stimulation. In this study, we performed TRH stimulation tests in 538 patients with ovulatory dysfunction. Only those patients showing a peak prolactin response after TRH which exceeded 40 ng/ml were treated with bromocriptine. A direct correlation between peak prolactin level after TRH and a favorable response to treatment was observed. Serum testosterone and DHEA-sulfate levels did not correlate with prolactin response to TRH. A majority of patients with prolactin hyperresponse to TRH did not show a hyperresponse of TSH to TRH. This study suggests that incidence of beneficial response to bromocriptine therapy in normoprolactinemic women with ovulatory dysfunction is significantly higher in subjects exhibiting excessive prolactin response to TRH stimulation.

Adult↗
PubMed1990

Pituitary disorders and pregnancy.

In conclusion, the physiologic changes that occur in the pituitary during pregnancy make women harboring pituitary tumors more vulnerable to tumor complications, namely tumor expansion resulting in either visual defects or hormone deficiencies. Fortunately, vast experience with the most common of these tumors (prolactinomas) allows us to make specific recommendations to women with such tumor embarking upon pregnancy. These recommendations have been outlined. In addition to tumors, the anterior lobe of the pituitary may be the seat of two rare conditions (Sheehan's syndrome and lymphocytic hypophysitis) that afflict pregnant women predominantly. Their importance lies in the fact that hypopituitarism, sometimes requiring urgent treatment, may result. Finally, pregnancy may have an unfavorable impact upon women with diabetes insipidus, necessitating careful observation. Given the availability of a specific and highly effective therapeutic agent, desmopressin acetate, the management of these women is rarely problematic.

Female↗
PubMed1988

Luteal-phase support in stimulated cycles in an in vitro fertilization/embryo transfer program: progesterone versus human chorionic gonadotropin.

A study was undertaken to compare the hormonal parameters [serum concentrations of estradiol (E2), and progesterone (P) and P/E2 ratios] of patients undergoing in vitro fertilization/embryo transfer to whom either progesterone in oil or human chorionic gonadotropin (hCG) was administered as luteal support. Seventeen patients were studied in 20 cycles. In 10 randomly assigned cycles 25 mg of intramuscular progesterone in oil was administered daily from the day of embryo transfer (day +4) until day +18. In the other 10 cycles, 1500 IU of hCG was given intramuscularly on days +4, +7, +10, and +13. Even when accounting for the differences in recruitment in the two groups, the hCG-treated group had significantly higher concentrations of serum P (P less than 0.01) and E2 (P less than 0.05) during the luteal phase. The luteal P/E2 ratios were higher in the progesterone-treated group because of the lower E2 levels in that group, although the difference was not statistically significant. The ratio of the mean luteal P to the preovulatory serum E2 was significantly higher in the hCG-treated group (P less than 0.01). There were three clinical pregnancies in the hCG-treated group. We conclude that (1) higher P concentrations are achieved with hCG treatment than with progesterone treatment during the luteal phase; (2) high luteal P/E2 ratios per se may not be an important determinant of implantation; (3) progesterone production by the corpus luteum is not maximal in progesterone-treated cycles; and (4) the usefulness of hCG as a luteal support agent should be further evaluated.

Chorionic Gonadotropin↗
PubMed1987

Absence of testicular protection by a gonadotropin-releasing hormone analogue against cyclophosphamide-induced testicular cytotoxicity in the mouse.

Protection of testicular integrity against damage from cyclophosphamide (CY) by simultaneous treatment with a gonadotropin-releasing hormone (GnRH) analogue was reported in BALB/c mice (L.M. Glode et al., Lancet, 1: 1132-1134, 1981). This approach has been used as the basis for clinical trials in various treatment centers (D. H. Johnson et al., Blood, 65:832-836, 1985) in an attempt to prevent iatrogenic sterility in males. This study aims at duplicating the original findings and obtaining quantitative data on spermatogonial killing by CY, and possible protection by GnRH, of differentiating and stem cell spermatogonia. Mice were treated with 23 daily injections of 0.4 micrograms D-leucine-6 GnRH, and with 200 mg/kg CY on Days 8, 15, and 22. Three additional groups of mice received phosphate-buffered saline and bovine serum albumin only, GnRH only, and CY only. Animals were killed at 29 days after the last injection to determine the number of late spermatids in testicular homogenates, and at 56 days for histological measurement of the ratio of elongated spermatids to Sertoli cells in the tubules. The twenty-ninth day assay was a measure of damage to differentiating spermatogonia, whose killing results in temporary sterility. The fifty-sixth day point assay assessed damage to stem spermatogonia, whose killing results in long-term or permanent sterility. Sperm counts at 29 days were identical in saline-treated control mice and GnRH-treated mice; no sperm were present in the CY-treated mice, both with and without GnRH. Thus, killing of differentiating spermatogonia by CY is not prevented by GnRH treatment. Similarly, counts of spermatids at 56 days showed no difference between saline- and GnRH-treated groups; a reduction to approximately 40% of control counts was observed equally with CY and CY plus GnRH treatments. Since GnRH treatment did not alter spermatogonial kinetics in BALB/c mice, it is not surprising that it did not protect against CY-induced damage. Thus, the mouse is not a suitable model for analyzing such effects of GnRH on spermatogenesis, and further studies in other experimental animals are needed if they are to be used as a rationale for clinical administration of GnRH to cancer patients.

Animals↗
PubMed1987

Patterns of increase in serum estradiol in response to ovarian stimulation and their relationship to oocyte fertilization and cleavage in vitro.

The in vitro fertilization and cleavage rates of oocytes obtained from patients exhibiting two different patterns of increase in serial serum concentrations of estradiol (E2) in response to ovarian stimulation were compared. Forty-two cycles (from 38 stimulated patients) were evaluated because they fulfilled requirements from two pre-defined patterns of E2 response to ovarian stimulation. In 16 cycles, serial serum E2 concentrations followed a "plateau" pattern (group A), viz., the rate of increase in the serum concentration of E2 decreased prior to the administration of human chorionic gonadotropin (hCG). In 26 cycles, serial serum E2 concentrations followed a "leap" pattern (group B), in which the rate of increase in serum concentrations of E2 increased progressively up to and including the day of hCG administration. There was no significant difference in the fertilization rate of oocytes obtained from patients exhibiting either pattern A or pattern B (78 versus 74%) but the cleavage rate was significantly higher in ova obtained from patients who exhibited pattern A rather than pattern B (72 vs 50%; P less than or equal to 0.01). In addition, embryos resulting from fertilized ova obtained from women in group A were of better quality morphologically than those obtained from women in group B (mean embryo grades, 3.9 vs 3.2; P less than or equal to 0.005). We conclude that cycles in which serial serum concentrations of E2 follow pattern A in response to stimulation give rise to oocytes that, when fertilized, yield higher cleavage rates and better-quality embryos than oocytes obtained from women in whom serial serum E2 concentrations follow pattern B.(ABSTRACT TRUNCATED AT 250 WORDS)

Chorionic Gonadotropin↗
PubMed1986

Characteristics of patients with and without gonadotropin surges during follicular recruitment in an in vitro fertilization/embryo transfer program.

Fifteen ovulatory patients undergoing ovarian stimulation with clomiphene citrate-human menopausal gonadotropin-human chorionic gonadotropin (hCG) for in vitro fertilization were studied. All 15 attained peak estradiol (E2) levels of greater than 600 pg/ml. Eight patients had an endogenous luteinizing hormone (LH) surge before the administration of hCG. The characteristics of these "surge" patients were compared with those of the remaining seven "nonsurge" patients. There was no significant difference in the peak morning E2 achieved before hCG or the endogenous LH surge, nor in the peak absolute increase in E2 over a 24-hour period in these two groups. The surge group had significantly higher E2 levels per follicle greater than or equal to 15 mm, measured by ultrasound on the morning of the day of administration of hCG or the LH surge (P less than or equal to 0.005). In addition, nonsurge patients had a greater number of follicles greater than or equal to 15 mm, compared with surge patients (P less than or equal to 0.05). It is hypothesized that greater quantities of nonsteroidal hormones, such as inhibin, produced by a greater number of preovulatory follicles in nonsurge patients, may block the pituitary response to hypothalamic gonadotropin-releasing hormone in the face of high and rising E2 levels.

Chorionic Gonadotropin↗
PubMed1986

Patterns of estradiol response in patients with endogenous gonadotropin surges during follicular recruitment in an in vitro fertilization and embryo transfer program.

This report is an analysis of 16 cycles in 15 patients stimulated with human menopausal gonadotropin and clomiphene citrate for the purpose of follicular recruitment in an in vitro fertilization program, all of which resulted in endogenous luteinizing hormone (LH) surges. A study of the pattern of estradiol (E2) response to stimulation revealed two groups of cycles, designated "leap" pattern (9 cycles) and "plateau" pattern (7 cycles), the rate of rise of E2 increasing or decreasing, respectively, as the time of the LH surge was approached. There were no significant differences between these groups of cycles in the peak E2 level attained or the number of follicles greater than or equal to 12 mm on the day of peak E2. In the plateau, but not in the leap pattern cycles, a significant correlation (r = 0.958) was found between the number of follicles greater than or equal to 12 mm and the peak E2. We tentatively conclude that "plateau" pattern cycles reflect relatively synchronous follicular recruitment; the greater the number of follicles recruited, the higher the E2 level attained, increased amounts of inhibin-like substances being available to restrain the LH surge; "leap" pattern cycles reflect asynchronous follicular recruitment.

Clomiphene↗
PubMed1986

Undetected ovulation in in vitro fertilization-embryo transfer patients.

A retrospective evaluation was done of 102 consecutive in in vitro fertilization-embryo transfer (IVF-ET) treatment cycles that culminated in surgical intervention for oocyte pickup. In 35% of these patients, a disparity was noted in the number of mature follicles present on the day of human chorionic gonadotropin administration, compared with the day of surgery. This suggests the occurrence of undetected ovulation. An endogenous luteinizing hormone (LH) surge was detected in 14 of these patients. Another cohort showed evidence of early luteinization without a detected endogenous LH surge. Finally, a group without early luteinization was defined. Possible explanations for these outcomes and the implications for success of IVF-ET are discussed.

Embryo Transfer↗