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Biomedical subjects

M C Martin

Publications and source records attributed to M C Martin.

At least 37 records · Page 2Linked to original sources

Assisted reproductive technologies: estimates of their contribution to multiple births and newborn hospital days in the United States.

OBJECTIVE: Estimate the contribution of assisted reproductive technology (ART) in the United States to multiple gestation births and newborn hospital days. DESIGN: Analysis of successful ART conceptions occurring during 1990 to 1991 compared with vital statistics. Newborn hospital days are estimated from the 1990 National Hospital Discharge Survey. SETTING: The American Fertility Society and the Society for Assisted Reproductive Technology registry. PATIENTS: Infants delivered from ART. INTERVENTIONS: Assisted reproductive technology. MAIN OUTCOME MEASURES: Number of multiple gestation infants and newborn hospital days. RESULTS: Approximately 12,327 live-born infants were delivered from ART conceptions during 1990 to 1991, representing 22.2% of all live-born triplet, 17.3% of quadruplet, and 11.4% of quintuplet infants born in the United States. The number of newborn hospital days attributed to ART infants was 87,135 days. Between the periods 1972 through 1974 and 1990 through 1991, the rate of triplet and higher order multiple gestation infants per 100,000 white live births increased by 191%, with 38% due to ART conceptions and 30% to increased childbearing among older women. CONCLUSIONS: Assisted reproductive technology contributed 22% of U.S. triplet and higher order multiple births during 1990 to 1991.

Female↗

Functional maturation of the primate fetal adrenal in vivo: I. Role of insulin-like growth factors (IGFs), IGF-I receptor, and IGF binding proteins in growth regulation.

The rapid growth of the primate fetal adrenal from midgestation until term is regulated by ACTH secreted by the fetal pituitary. Previous studies suggest that the trophic actions of ACTH are mediated by insulin-like growth factor II (IGF-II) synthesized by fetal adrenal cortical cells. To characterize further the role of IGF-II in the regulation of fetal adrenal growth, we investigated the expression of the messenger RNAs (mRNAs) encoding IGF-I, IGF-II, IGF-I receptor (IGF-IR) and IGF binding protein (IGFBP) 1-6 in the fetal rhesus monkey adrenal in vivo from 109 days of gestation until term (165 +/- 5 days) using in situ hybridization. To assess the role of ACTH in the regulation of expression of the IGF system in vivo, we administered metyrapone (3-7 days) to late gestation fetal rhesus monkeys (n = 4) in utero to increase fetal pituitary ACTH secretion. IGF-II mRNA was abundant in the definitive, transitional and fetal zones of the adrenal cortex from 109 days until term. IGF-IR mRNA was expressed in the definitive, transitional and fetal zones and decreased to nondetectable levels at term. IGFBP-2 and IGFBP-6 mRNAs were expressed in the definitive, transitional, and fetal zones, whereas IGFBP-1, -3, -4, and -5 were not detected in adrenal cells. The effects of increasing ACTH secretion on the growth of the specific zones of the adrenal were determined using morphometric techniques. Metyrapone treatment approximately doubled adrenal weight, which was due to an increase in the area of the definitive, transitional, and fetal zones with decreased cell density of the definitive, transitional, and fetal zones compared with controls and not due to a change in total cell number. Therefore, the increase in adrenal weight after metyrapone treatment was due to hypertrophy of the three cortical zones; there was no effect on adrenal medullary growth. The relative abundance of the mRNAs encoding IGF-II and the IGF-IR was increased after metyrapone treatment, whereas the localization and relative abundance of IGFBP 1-6 mRNAs were not altered by metyrapone treatment. We conclude that the ontogenetic increase in adrenal growth may be regulated, at least in part, by locally synthesized IGF-II, and the cessation of adrenal growth that occurs at term may be mediated by the decrease in the IGF-IR. The adrenal cortical expression of IGFBP-2 and IGFBP-6 suggests that these IGFBPs may modulate the IGF-IGF-IR interaction. Metyrapone treatment, which likely increased fetal pituitary ACTH secretion, causes a coordinated increase in expression of IGF-II and IGF-IR in fetal adrenal cortical cells, which may be an important mechanism of regulation of fetal adrenal cortical growth.

Adrenal Glands↗

Functional maturation of the primate fetal adrenal in vivo. II. Ontogeny of corticosteroid synthesis is dependent upon specific zonal expression of 3 beta-hydroxysteroid dehydrogenase/isomerase.

Cortisol, produced by the primate fetal adrenal, regulates the maturation of organ systems necessary for extrauterine life. During most of primate pregnancy, however, the fetal adrenal lacks the enzyme 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta HSD), which is essential for cortisol synthesis. Therefore, we used immunohistochemistry and in situ hybridization techniques to investigate the developmental expression of 3 beta HSD in the fetal rhesus monkey adrenal from 109 days' gestation until term (165 +/- 5 days) and assessed the role of ACTH in the induction of its expression and localization. We also examined whether ACTH regulates the expression of two other steroidogenic enzymes, cytochrome P450 cholesterol side-chain cleavage (P450scc) and P450 17 alpha-hydroxylase, 17/20-lyase (P450c17), in the fetal rhesus monkey adrenal. To stimulate ACTH secretion from the fetal pituitary in vivo, we administered metyrapone to late gestation fetal rhesus monkeys for 3-7 days. Adrenals were collected from untreated fetuses at 109-125 days (n = 5), 130-148 days (n = 7), 155-172 days (n = 4), and after metyrapone treatment at 135-137 days (n = 4). The cortical width and total amount of 3 beta HSD staining were measured using an image analysis system. 3 beta HSD was localized primarily in the definitive zone cells of the adrenal from fetuses between 109-148 days, whereas at term (155-172 days), 3 beta HSD was localized in both definitive and transitional zone cells. The cortical width and total amount of 3 beta HSD staining in the adrenal increased significantly (P < 0.05) between 148 days (137 +/- 14 microns and 3,689 +/- 522 grains) and 155 days (315 +/- 61 microns and 7,321 +/- 2,008 grains). Interestingly, in metyrapone-treated fetuses at 135-137 days, 3 beta HSD messenger RNA (mRNA) and protein were localized extensively in both the definitive and transitional zones, a pattern seen only in term fetal adrenals in untreated animals. In addition, metyrapone treatment significantly (P < 0.05) increased cortical width (386 +/- 95 microns) and total 3 beta HSD immunostaining (29,063 +/- 13,692 grains) compared with age-matched controls. In contrast to 3 beta HSD, P450scc mRNA was detected in the definitive, transitional, and fetal zones, and its expression was not altered after metyrapone treatment. P450c17 mRNA was detected in the transitional and fetal zones, and the relative abundance was greater in the transitional zone. The relative abundance of P450c17 mRNA was increased in the fetal zone after metyrapone treatment. In summary, at term or after metyrapone treatment, expression of 3 beta HSD is induced in the transitional zone of the fetal rhesus monkey adrenal gland, an indication of functional maturation of the primate adrenal cortex. These data suggest that the ontogenetic increase in fetal pituitary ACTH secretion plays an important role in the induction of 3 beta HSD expression in the transitional zone.

Adrenal Cortex Hormones↗

Transjugular intrahepatic portosystemic shunt with the Strecker stent for control of refractory acute and chronic variceal bleeding.

BACKGROUND: We wanted to assess prospectively the safety, efficacy, and applicability of transjugular intrahepatic portosystemic shunt (TIPS) with the Strecker stent, focusing mainly on clinical and hemodynamic medium- and long-term follow-up. METHODS: Fifty-two patients reached an indication to perform a TIPS, in an emergency or after refractory variceal bleeding. It was completed in 50 of them. All presented with cirrhosis (Child C = 15, B = 23, A = 12). The prosthesis was a Strecker stent. During the follow-up, clinical, biochemical, endoscopic, ultrasound, and pressure measurement studies were performed at 1, 3, 6, 12 months. Mean follow-up was 13.5 + or - 7.8 months. RESULTS: Portal pressure decreased from 32.3 + or - 8.1 (mean + or - standard deviation) to 22.3 + or - 6.7 mm Hg and portocaval gradient from 21 +/- 5.2 to 8.7 +/- 3.9 mm Hg (average, 56 + or - 16%). Shunt dysfunction was diagnosed when the portocaval gradient was >12 mm Hg (20 patients). Eleven patients (22%) presented with variceal rebleeding because of shunt dysfunction. The probability of remaining free of bleeding was 78%, 74%, and 68% at 6, 12, and 24 months, respectively. Actuarial survival rate was 91% and 86% after 12 and 18 months, respectively. CONCLUSION: TIPS with the Strecker stent is a safe alternative for variceal bleeding. Shunt dysfunction is frequent and increases the rebleeding rate, requiring a close follow-up with pressure measurements. Randomized trials comparing stents and other alternatives are needed to fully address the role of this procedure.

Acute Disease↗

The choice of a gonadotropin-releasing hormone analog influences outcome of in vitro fertilization treatment.

OBJECTIVE: Our purpose was to determine if there is a difference in outcome associated with choice of gonadotropin-releasing hormone analog in in vitro fertilization treatment cycles. STUDY DESIGN: A retrospective analysis of 510 consecutive in vitro fertilization cycles with patient-selected use of either nafarelin (Synarel) or leuprolide (Lupron) was performed. RESULTS: Of 510 consecutive patient cycles, 284 patients (56%) chose nafarelin and 226 (44%) chose leuprolide. In the nafarelin group 64 cycles (34% of retrievals) resulted in deliveries. In the leuprolide group 37 (24%) resulted in delivery (p < 0.05). There were 260 patients in their first cycle of treatment, with 157 (60%) choosing nafarelin, resulting in 33 deliveries (34% per retrieval). Leuprolide, used in 103 (40%) of first cycles, resulted in 12 deliveries (20% per retrieval), (p = 0.052). CONCLUSIONS: In a large population of unselected patients undergoing in vitro fertilization the choice of nafarelin was associated with a significantly better outcome in terms of successful pregnancies achieved.

Adult↗

Elevated serum progesterone levels on the day of human chorionic gonadotropin administration do not predict outcome in assisted reproduction cycles.

OBJECTIVE: To determine if the level of serum P drawn on the day of hCG administration predicts assisted reproductive technology (ART) outcome in patients undergoing stimulation with hMG under GnRH agonist (GnRH-a) suppression. DESIGN: Retrospective P assay of stored serum. PATIENTS: One hundred seventy-one patients (189 cycles) who had undergone GnRH-a suppression (leuprolide acetate or nafarelin) and stimulation with hMG for an ART procedure. MAIN OUTCOME MEASURES: Progesterone RIA of serum obtained on the day of hCG administration. Measurement of sequential serum LH values by RIA in those patients with the highest P levels. RESULTS: Pregnancy rates per oocyte retrieval were not correlated with the P level before hCG administration. There were 18 of 54 (33.3%) clinical pregnancies in those cycles with P < 0.9 ng/mL (conversion factor to SI unit, 3.180) and 42 of 135 (31.1%) clinical pregnancies in cycles with a P > or = 0.9 ng/mL. Significantly higher serum E2 levels and numbers of of follicles and oocytes obtained were observed in the high P cycles. There were no differences in the number of oocytes fertilized, the number of embryos transferred, or the implantation rate. However, a significantly higher percentage of mature oocytes were fertilized in the low P cycles (73%), as compared with the high P cycles (60%). CONCLUSIONS: Serum P levels before hCG administration do not predict the outcome of ART cycles in patients suppressed with GnRH-a before hMG stimulation. Lower fertilization rates observed in the high P cycles did not have an effect on clinical outcome.

Chorionic Gonadotropin↗

Menopause without symptoms: the endocrinology of menopause among rural Mayan Indians.

OBJECTIVE: Our purpose was to determine the characteristics of menopause among Mayan women who did not have menopausal symptoms. STUDY DESIGN: A cross-sectional study of Mayan women from Chichimila, Mexico, was performed. Demographic information, history and physical examination, hormone concentrations, and radial bone density measurement were obtained. RESULTS: Fifty-two postmenopausal women were compared with 26 premenopausal women. Menopause occurred at 44.3 +/- 4.4 years. None of the women admitted to hot flushes and did not recall significant menopausal symptoms. Hormone levels included elevated follicle-stimulating hormone (66.6 +/- 29 mlU/ml), low estradiol and estrone (9.4 +/- 8.3 and 13.3 +/- 7.8 pg/ml), estrone greater than estradiol levels, normal levels of testosterone and androstenedione (0.17 +/- 0.14 and 0.31 +/- 0.17 ng/ml). Bone mineral density declined with age, but height did not. Clinical evidence of osteoporosis was not detected. CONCLUSIONS: Lack of symptoms during the menopausal transition is not attributable to a difference in endocrinology. Postmenopausal Mayan women are estrogen deprived and experience age-related bone demineralization but do not have a high incidence of osteoporotic fractures.

Adult↗

Defining and interpreting pregnancy success rates for in vitro fertilization.

OBJECTIVES: To review current practice in describing pregnancy success rates after IVF-ET, to identify issues associated with interpreting these rates, and to suggest useful methods of describing these rates in the future. DESIGN: Review of literature concerning medical, epidemiologic, and statistical aspects of reporting IVF-ET pregnancy success rates. SETTING: The United States. PATIENTS: Infertile couples participating in IVF-ET. MAIN OUTCOME MEASURES: Usefulness and accuracy of IVF-ET pregnancy reporting. RESULTS: Several groups have collected information on the pregnancy success rates of IVF-ET clinics and have discussed appropriate definitions of pregnancy success. The largest of these groups in the United States is The American Fertility Society and its affiliate, the Society for Assisted Reproductive Technology. The number of live deliveries per 100 ET procedures and the number of live deliveries per 100 egg retrieval procedures are among the most commonly used definitions. CONCLUSION: The most commonly used definitions are particularly useful for describing the probability that a live infant will be delivered after IVF-ET is completed. To measure the effectiveness of the IVF-ET procedures and the costs of undergoing IVF-ET, other definitions are also important. Success rates need to be stratified by patient characteristics, such as age, that affect the probability of success.

Data Collection↗

Evaluation of natural family planning programmes in Liberia and Zambia.

Studies to evaluate use-effectiveness and cost-effectiveness of natural family planning (NFP) were conducted in Liberia and Zambia. The Liberian programme provided uni-purpose NFP services to 1055 clients mainly in rural areas; the Zambian programme provided NFP services integrated with MCH to 2709 clients predominantly in urban areas. The one-year life table continuation and unplanned pregnancy rates were 78.9 and 4.3 per 100 woman-years in Liberia, compared to 71.2 and 8.9 in Zambia. However, high rates of loss to follow-up mandate caution in interpretation of these results, especially in Zambia. More women progressed to autonomous NFP use in Liberia (58%) than in Zambia (35.3%). However, programme costs per couple-year protection were lower in Zambia (US$25.7) than in Liberia (US$47.1). Costs per couple-year protection were higher during learning than autonomy, and declined over time. These studies suggest that NFP programmes can achieve acceptable use- and cost-effectiveness in Africa.

Adult↗

Response to hemorrhagic stress in the rhesus monkey fetus in utero: effects on the pituitary-adrenal axis.

In human pregnancy, fetoplacental hemorrhage is often associated with morbidity and potentially mortality. We investigated the effect of acute fetal hemorrhage on the fetal pituitary-adrenal axis in the subhuman primate (Macaca mulatta). We measured fetal and maternal plasma concentrations of ACTH, cortisol, and dehydroepiandrosterone sulfate (DHAS) by RIA in 10 rhesus monkeys. At 133-158 days of gestation (d) the fetuses were subjected to acute hemorrhage (0.5 mL/min for 10 min). Fetal plasma ACTH and cortisol concentrations were significantly increased above baseline in response to fetal hemorrhage. There was a more rapid, but significantly reduced, fetal plasma ACTH and cortisol response in the 133-143 d fetuses than in the 147-158 d fetuses. In 133-143 d fetuses, the maximal changes from baseline in plasma ACTH and cortisol concentrations were +6.5 +/- 2.6 pmol/L at +25 min and +4.55 +/- 1.19 nmol/L at +10 min, respectively. Fetal plasma ACTH and cortisol concentrations remained elevated throughout the 60-min period after hemorrhage (3.06 +/- 1.21 pmol/L and +2.42 +/- 1.05 nmol/L at +70 min). In 147-158 d fetuses, the maximal changes from baseline in plasma ACTH and cortisol concentrations were +13.7 +/- 4.23 pmol/L and +12.92 +/- 3.25 nmol/L at +70 min. In the 133-143 d fetuses, plasma DHAS concentrations did not change in response to hemorrhage, whereas in the 147-158 d fetuses, plasma DHAS concentrations were elevated above baseline during the hemorrhage (+624.2 +/- 269.5 nmol/L, at +9 min) and returned quickly to pre-hemorrhage values. These data suggest that the fetal pituitary-adrenal axis plays a role in the fetal response to intrauterine stress, but that only later in gestation is the fetal cortisol response to fetal hemorrhage mediated via ACTH secreted by the fetal pituitary.

Adrenocorticotropic Hormone↗

Preimplantation diagnosis.

Preimplantation embryonic biopsy and analysis offer couples at increased risk of having offspring affected with a genetic disorder the possibility of an early prenatal diagnosis. For many couples, this approach would avoid the issue of the selective termination of affected fetuses. Substantial advances have been made in the area of preimplantation diagnosis, but the possible difficulties with this approach cannot be ignored.

Animals↗

Lymphocytic adenohypophysitis: a pituitary mass lesion occurring in pregnancy. Proposal for medical treatment.

Lymphocytic adenohypophysitis is a nonneoplastic, autoimmune cause of pituitary enlargement and insufficiency. Forty-eight of the 50 reported cases have occurred in women, nearly all in association with pregnancy. Left undiagnosed and untreated, it can progress to pituitary insufficiency and death. Histologic studies show characteristic changes of autoimmune disease with lymphocytic infiltration and destruction of anterior pituitary tissue with fibrotic replacement. Lymphocytic adenohypophysitis is currently diagnosed after other pituitary mass lesions are excluded and has been treated with a combination of neurosurgery and end-organ hormone replacement. However, with improved knowledge of the pathophysiologic characteristics and natural history of the disease and with the ability to make a prospective diagnosis, we believe glucocorticoids may suppress the inflammatory response and protect remaining pituitary tissue. Two previously unreported pregnancy-associated cases are described, including one prospectively diagnosed and treated without neurosurgery during pregnancy. Obstetrician-gynecologists must place lymphocytic adenohypophysitis in the differential diagnosis of pituitary enlargement associated with pregnancy, since treatment is available and the sequelae may be life-threatening.

Adult↗

Maturation of immature oocytes by coculture with granulosa cells.

To increase the number of embryos available for transfer, immature human oocytes were cocultured with granulosa cells from preovulatory follicles. Greater numbers of immature oocytes incubated with granulosa cells had dispersion of the cumulus and corona cells compared with immature oocytes cultured in media alone. Fifty-four percent of immature oocytes were fertilized after coculture with granulosa cells compared with 20% fertilization of immature oocytes cultured without granulosa cells. There were no cases in which only embryos developed from immature oocytes were transferred, and thus we could not determine if the immature oocytes could contribute to a pregnancy.

Cell Communication↗

Development of a circadian variation of plasma oxytocin concentration in the late gestation rhesus monkey.

The 24-h pattern of oxytocin (OT) concentrations in maternal plasma was investigated serially from 112-168 days gestation in four chair-restrained pregnant rhesus monkeys. No change in the mean daily plasma OT concentration was observed with advancing gestational age; there was a change in the pattern of plasma OT secretion throughout the period, however. About 21 days from delivery (150.8 +/- 1.8 days gestational age), plasma OT levels showed occasional fluctuations, distributed throughout the day. About 8 days from delivery (163.2 +/- 2.4 days gestational age), a clear circadian pattern of OT was detected, with an acrophase at 2200 h. These results suggest that there is a relationship between the pattern of OT secretion and advancing pregnancy. This may account partially for the increase in uterine activity known to occur in term rhesus monkeys.

Animals↗

Recent advances in the management of sexual precocity in girls.

Sexual precocity has important psychosocial implications for the prematurely developing child, as well as being associated in some cases with significant pathology. Conscientious evaluation and initiation of effective therapy can have a significant impact on improving long-term outcome. The differentiation between complete sexual precocity with activation of the hypothalamic-pituitary axis and incomplete sexual precocity without activation of the central reproductive system is of paramount importance. In incomplete sexual precocity, the sex steroids are of exogenous, adrenal, or gonadal origin. Premature adrenarche presents with the early development of pubic hair only and must be distinguished from adrenal hyperplasia or an androgen-secreting neoplasm, which may be associated with accelerated growth, advanced bone age, and virilization. When incomplete sexual precocity involves the ovary, ovarian tumors must be considered. Other causes of incomplete sexual precocity include hypothyroidism and gonadotropin-independent precocity such as McCune-Albright syndrome. Complete sexual precocity or precocious puberty of central origin is diagnosed in girls by gonadotropin-releasing hormone challenge yielding a stimulated luteinizing hormone peak greater than 15 IU/L. Radiologic evaluation of the central axis is necessary. Treatment of precocious puberty relies on the use of potent agonists of gonadotropin-releasing hormone that reversibly suppress the prematurely activated pituitary. Depot preparations are efficacious. Early initiation and careful monitoring of treatment can reduce physical signs of development, improve the likelihood for normal adult height, and postpone normal pubertal progression to a more appropriate age.

Child↗

Effect of previous supramaximal work on lacticaemia during supra-anaerobic threshold exercise.

Twelve male and female subjects (eight trained, four untrained) exercised for 30 min on a treadmill at an intensity of maximal O2 consumption (% VO2max) 90.0%, SD 4.7 greater than the anaerobic threshold of 4 mmol.l-1 (Than = 83.6% VO2max, SD 8.9). Time-dependent changes in blood lactate concentration [( lab]) during exercise occurred in two phases: the oxygen uptake (VO2) transient phase (from 0 to 4 min) and the VO2 steady-state phase (4-30 min). During the transient phase, [lab] increased markedly (1.30 mmol.l-1.min-1, SD (0.13). During the steady-state phase, [lab] increased slightly (0.02 mmol.l-1.min-1, SD 0.06) and when individual values were considered, it was seen that there were no time-dependent increases in [lab] in half of the subjects. Following hyperlacticaemia (8.8 mmol.l-1, SD 2.0) induced by a previous 2 min of supramaximal exercise (120% VO2max), [lab] decreased during the VO2 transient (-0.118 mmol.l-1.min-1, SD 0.209) and steady-state (-0.088 mmol.l-1.min-1, SD 0.103) phases of 30 min exercise (91.4% VO2max, SD 4.8). In conclusion, it was not possible from the Than to determine the maximal [lab] steady state for each subject. In addition, lactate accumulated during previous supramaximal exercise was eliminated during the VO2 transient phase of exercise performed at an intensity above the Than. This effect is probably largely explained by the reduction in oxygen deficit during the transient phase. Under these conditions, the time-course of changes in [lab] during the VO2 steady state was also affected.

Adult↗

Neuromodulatory regulation of gonadotropin-releasing hormone pulsatile discharge in women.

The pulsatile release of gonadotropin-releasing hormone and the consequent secretion of gonadotropins are regulated by a complex interplay of steroids, neuropeptides, catecholamines, and environmental factors. Estrogen and progesterone influence the amplitude and frequency of luteinizing hormone pulsatile secretion. These effects lead to both a diurnal variation in pulse frequency, with a lower frequency at night, and variation during the menstrual cycle, with a lower frequency and increased amplitude during the luteal phase. Opioid peptides inhibit the pulsatile discharge of gonadotropin-releasing hormone and luteinizing hormone. The opioid antagonist, naloxone, causes an increase in luteinizing hormone secretion, particularly during the luteal phase. The administration of opioid receptor agonists, such as beta-endorphin, results in a decline in serum luteinizing hormone during the early follicular phase. Corticotropin-releasing factor, which is increased during stress, inhibits pulsatile luteinizing hormone secretion, and this effect can be blocked by the simultaneous administration of naloxone. These observations suggest that corticotropin-releasing factor exerts its effects on luteinizing hormone through an opioidergic intermediary. Endogenous catecholamines such as dopamine inhibit pulsatile luteinizing hormone release; however, the mechanism involved is not clear.

Adult↗