PubMed HealthSearch

Biomedical subjects

R Fleming

Publications and source records attributed to R Fleming.

At least 19 recordsLinked to original sources

Absence of effect of adjuvant growth hormone therapy on follicular responses to exogenous gonadotropins in women: normal and poor responders.

OBJECTIVE: To examine the effects of growth hormone (GH) on ovarian responses to exogenous gonadotropins after pituitary desensitization in normal and poor responder patients undergoing in vitro fertilization. DESIGN: A prospective study with comparison of control and GH-treated cycles. PATIENTS: Poor responder patients (n = 10) required > 44 ampules of human menopausal gonadotropin (hMG) to achieve criteria for administration of human chorionic gonadotropin (hCG) on day 0 or cancellation in control cycles, and normal responder patients (n = 10) required < 45 ampules. MAIN OUTCOME MEASURES: Ovarian responses to hMG assessed by duration of stimulation required to achieve first significant estradiol (E2) response and hCG criteria. Total doses and duration of hMG, follicular development and E2 concentrations on day 0, and embryology were also assessed. RESULTS: Growth hormone showed no effect on any of the parameters studied in either patient group. CONCLUSION: Follicular recruitment, E2 secretion by mature follicles, and oocyte yield and quality were uninfluenced by GH treatment.

Adult

In vivo and in vitro maturation of human oocytes: effects on embryo development and polyspermic fertilization.

OBJECTIVE: To compare the effects of in vivo and in vitro maturation of human oocytes. DESIGN: Women (n = 60) undergoing follicular stimulation for in vitro fertilization, using long-course analog therapy to suppress endogenous luteinizing hormone (LH), were randomly allocated to a short (34 hour) or long (39 hour) delay between human chorionic gonadotropin (hCG) administration and oocyte retrieval. Each patient's oocytes were divided into two groups that were either inseminated immediately or after 5 hours. RESULTS: The incidence of polyspermic fertilization was highest in oocytes inseminated immediately after a short hCG/oocyte retrieval interval (17/100) and was significantly (P less than 0.05) reduced by preincubation and/or a long hGG/oocyte retrieval interval. Fertilization rates were higher with 39 hours than with 34 hours in vivo maturation (84.2% versus 76.8%; P less than 0.05). The incidence of delayed fertilization was reduced by extending the hCG/oocyte retrieval interval (short, 12.9%; long, 3.9%; P less than 0.001). CONCLUSIONS: Extension of the in vivo maturation time increased fertilization rates and eliminated the requirement for preinsemination incubation, allowing simplification of laboratory procedures.

Chorionic Gonadotropin

Luteinization to oocyte retrieval delay in women in whom multiple follicular growth was induced as part of an in vitro fertilization/gamete intrafallopian transfer program.

Different luteinization-to-oocyte-retrieval delays were examined in 64 IVF/GIFT patients. Multiple follicular stimulation was induced with combined therapy of hMG and GnRH-a to create continuous pituitary suppression and thus eliminate endogenous gonadotropin fluctuations. The results demonstrated that with this induction regime, the time interval can be extended to 39 hours without preoperative ovulation and with improved oocyte maturity.

Buserelin

Induction of multiple follicular development for IVF.

It is now accepted, almost universally, that multiple follicular development is a pre-requisite for a successful assisted conception programme. The reasons for this are based on abundant clinical evidence from the major IVF and GIFT centres of the world indicating the benefits of having multiple gametes available for transfer. The more embryos transferred, the better the pregnancy rate; the more embryos available for cryopreservation the better the chances of subsequent survival and replacement. However, the vast majority of patients in IVF/GIFT programmes have normal ovarian and pituitary function designed to produce a single dominant follicle and oocyte each month. Obtaining multiple follicular growth requires pharmacological manipulation of ovarian function and complicating factors may arise from both ovarian and pituitary sources. Methods employed to achieve multiple follicular growth vary considerably in the different centres and experiments continue in attempts to find either the simplest or the perfect system, or both. This would provide abundant oocytes and the ideal hormone environment for implantation, with no interfering factors at either the ovarian or endometrial level, while avoiding the drawbacks commonly encountered such as pre-operative ovulation or hyperstimulation syndrome. It should also be inexpensive, although in reality cost-effectiveness is more important.

Female

Ovarian sensitivity to gonadotrophins in patients with PCO is unaffected by suppression of LH.

Infertile women with oligomenorrhoea and elevated LH concentrations (presumed polycystic ovary disease, PCO) were treated with exogenous gonadotrophins, HMG and HCG, for induction of follicular growth and ovulation, respectively. This was effected in the absence or presence of a gonadotrophin releasing hormone analogue (GnRH-A) to suppress basal LH and the positive feedback surge of LH. Analyses of the duration of HMG therapy required to attain the degree of stimulation for HCG to be administered showed no difference between those with and without LH suppression. Analyses of the ultrasound estimations of rates of follicle growth and continued recruitment during the course of HMG also failed to show any effect of LH suppression. These data show that the high sensitivity of these patients to HMG is not related to the circulating LH concentrations.

Buserelin

Luteal phase deficiency: ultrasonic and biochemical insights into pathogenesis.

Serial ovarian ultrasound and daily assessments of plasma concentrations of pituitary and ovarian hormones were used to investigate ovarian function in 175 women with unexplained infertility. Their endocrine and ultrasound profiles were compared with similarly derived data from 43 normal volunteers. Fifty-one (29.1%) of the study group showed subnormal luteal phase rises in progesterone concentrations, described as poor progesterone surge (PPS) cycles. Within this group, 23 women (45.1%) demonstrated luteal cyst formation, a pattern not seen in any of the control cycles. High concentrations of follicle stimulating hormone (FSH) and reduced concentrations of oestradiol (E2) were observed in the follicular phases of the PPS cycles suggesting that the phenomenon is a product of abnormal follicular metabolism. An association of PPS with infertility exists, perhaps related to a combination of disturbances in the follicular micro-environment compromising oocyte quality, a failure of oocyte release, and impaired endometrial receptivity.

Adult

The role of the tibial nutrient artery. Microsphere estimation of blood flow in the osteotomised canine tibia.

There has been a long-standing debate as to whether medullary or periosteal flow is the dominant vascular supply during the healing of diaphyseal fractures. We used radioactive microspheres to quantify blood flow to the canine tibia two weeks after an osteotomy. There was a significant contribution from the periosteum to the blood supply of healing cortical bone after nutrient artery ligation, with a reversal of flow from a centrifugal to a centripetal direction. Our study has confirmed the qualitative observations of Trueta (1974) regarding the significant recruitment of vessels from surrounding soft tissue during fracture healing. We have not studied the later stages of healing.

Animals

Luteal cysts and unexplained infertility: biochemical and ultrasonic evaluation.

A prospective, controlled study of ovarian function using ovarian ultrasound and daily plasma hormone estimations (estradiol, progesterone [P], follicle-stimulating hormone [FSH], luteinizing hormone [LH]) was carried out on 175 spontaneously cycling patients with unexplained infertility. Forty-one (23.4%) demonstrated luteal phase cyst formation. In 21 cycles the dominant follicle reduced in size after the LH peak (cystic corpus luteum cycles), and in 20 no shrinkage was seen (luteinized unruptured follicles). Progesterone concentrations in the early luteal phase were significantly reduced in the luteinized unruptured follicle cycles. Elevation in plasma FSH was seen in the early follicular and luteal phases of both cyst forming groups and may be due to disturbances in ovarian metabolism. Follicular rupture is important for efficient P release by the corpus luteum.

Adult

Biogenesis of plasma lipoproteins in rat hepatoma McA-RH7777: importance of diffusion-mediated events during cell growth.

Cultured McA-RH7777 rat hepatoma cells actively synthesize and secrete plasma lipoproteins. However, synthesis of [14C]triglyceride declines monotonically throughout the early growth period and remains low in postconfluent cultures; and net secretion of [14C]triglyceride is 10-fold more efficient in logarithmically growing cultures than in postconfluent cultures. Secretion of apolipoproteins associated with very low density and low density lipoproteins is selectively reduced in postconfluent cultures. The temporal reductions in [14C]triglyceride production are related more strongly to increasing cell concentration (cells/cm3 medium) than to increasing cell density (cells/cm2 growth surface). We have allowed cells to grow either retained within small circular corrals or unrestricted in culture dishes. When seeded at equal density (10(4) cells/cm2) but at one-fifth the cell concentration, corralled cells synthesize twice as much [14C]triglyceride per cell after 2 and 4 d, and are 10 times as efficient in [14C]triglyceride secretion by 6 d of growth, as noncorralled cells. When seeded at equal cell concentration (10(5) cells/dish) but at 5 times the cell density, corralled cells are only 20% less efficient at [14C]triglyceride synthesis and secretion than noncorralled cells. Conditioned medium depresses synthesis and secretion efficiency of [14C]triglyceride. Orotic acid exposure also inhibits synthesis of [14C]triglyceride and secretion of certain [35S]apolipoproteins in early cultures, but it has no significant effect on late cultures. We conclude that diffusion-mediated events are important regulators of triglyceride and apolipoprotein production in growing rat hepatoma cells, but that events associated with formation of cell-to-cell contacts play a minor role in regulation of plasma lipoprotein biogenesis.

Albumins

The quitting experience for smokers in sixth through twelfth grades.

The present study examined the withdrawal process for adolescents who had attempted to quit smoking. A sample of 622 6th through 12th graders were interviewed. Smoking status was reported prior to attempting to quit and its relationship with the withdrawal experience was evaluated. Although over half of those who smoked regularly reported trying to quit, 78% of the "quitters" were smoking six months after their quit attempt. Experiencing adverse withdrawal symptoms was related to smoking at daily levels before quitting; delaying trying to quit was associated with initiation of smoking at an early age; and quitting success was predicted by early quitting age, lower pre-quitting smoking levels, a lack of a prior quitting failure, and peer smoking. The results suggest that smoking intervention programs for adolescents should include components facilitating the quitting process that take into consideration youngsters' smoking and quitting histories.

Adolescent

The role of cigarettes in the initiation and progression of early substance use.

This study examined progression in substance use from initiation to eventual regular use and provided information on a number of levels. Cigarette use was shown to fall on a cumulative (Guttman) scale of use with other drugs (e.g., marijuana, beer, liquor, stimulants or depressants). Also, cigarettes were the drug with the youngest mean age of onset which would still fall on a Guttman scale with other drugs shown to scale in previous research. Finally, it was shown that having tried only cigarettes or marijuana made one significantly more likely to be using other drugs two years later.

Adolescent

Combined gonadotropin-releasing hormone analog and exogenous gonadotropins for ovulation induction in infertile women: efficacy related to ovarian function assessment.

The ovarian function of infertile women with normal menstrual rhythm was investigated by daily plasma hormone (estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone) analyses throughout the menstrual cycle, and patients were diagnosed as showing a subnormal profile of progesterone in the early luteal phase or as showing no abnormality. Women with oligomenorrhea and elevated luteinizing hormone levels were diagnosed as having polycystic ovary syndrome primarily on the basis of endocrinology. All patients were treated with a gonadotropin-releasing hormone analog to suppress endogenous luteinizing hormone and follicle-stimulating hormone so that ovulation induction with exogenous gonadotropins could be undertaken as in patients with hypogonadotropic hypogonadism. Interference in the process of ovulation by endogenous luteinizing hormone fluctuations was eliminated and pregnancies were achieved. The pregnancy rate in the group with polycystic ovary syndrome was 77% per treatment course (six cycles) while that in the group with subnormal progesterone profiles was 61.5%. Patients showing no abnormality achieved no pregnancy, demonstrating the redundancy of interference with normal ovarian function.

Adult

LHRH analogues for ovulation induction, with particular reference to polycystic ovary syndrome.

Infertile women with PCO have been treated with exogenous gonadotrophins (hMG/hCG) for ovulation induction either with or without LHRH-agonist treatment. Those treated without LHRH-agonist-induced LH suppression showed PL in greater than 30% of the cycles and this problem was eliminated by LHRH-agonist therapy. The pregnancy rate (approximately 80% of patients) during the combined therapy was approximately twice that of the group treated with hMG/hCG alone. The suppression of endogenous LH by the LHRH-agonist appeared to have no effect upon the profiles of follicular development in response to hMG, and a high rate of follicle recruitment characterized all PCO treatment cycles irrespective of circulating LH concentrations. These results suggest that LH suppression improves the efficacy of ovulation induction but has no influence on the primary metabolic disturbance in the PCO syndrome.

Drug Therapy, Combination

Health aspects of radio-frequency radiation accidents. Part I: Assessment of health after a radio-frequency radiation accident.

The health aspects of an accident involving nine men exposed to 4.1 GHz radio-frequency radiation (RFR) is described. Two were exposed to levels of 4.6 mW/cm2 for up to 90 minutes, which exceeds the current Australian standard of 1 mW/cm2, while the other seven were exposed to lower levels. For staff in the high-exposure group, the dose rate was calculated for the whole body, skin, eyes, and pituitary. Comprehensive medical examinations were performed on all staff, including follow-up ophthalmological examinations over a period of nine months. Various abnormalities were found in all staff but, with the possible exception of hair loss, there was no consistent gradient of effect in the occurrence of abnormality between the groups. Various problems in conducting the investigation are discussed. It was concluded that the exposure had not resulted in harmful effects.

Accidents, Occupational

The use of GnRH analogues in combination with exogenous gonadotropins in infertile women.

GnRH analogues suppress LH fluctuations and produce a condition of hypogonadotropic hypogonadism. This action combined with treatment with human menopausal gonadotropins (hMG) has been exploited in programmes of induction of follicular growth in infertile women for both in vivo and in vitro fertilisation. There is improved clinical control over the process of ovulation and the phenomenon of premature luteinization in women with polycystic ovary disease has been eliminated.

Drug Therapy, Combination

Apolipoproteins of the orotic acid fatty liver: implications for the biogenesis of plasma lipoproteins.

Rats fed orotic acid develop fatty livers characterized by triglyceride-laden, membrane-bounded vesicles designated "liposomes." We have measured the levels of apolipoproteins in isolated liposomes and other subcellular fractions by SDS-polyacrylamide gel electrophoresis, electrotransfer, and immunodecoration. Apolipoproteins Bh, Bl, E, and C appear to cofractionate; for these proteins, the liposomal pool represents a large portion of their total intracellular mass. However, liposomes are deficient in both variants of apoB relative to apoE and apoC when compared with rat plasma very low density lipoprotein (VLDL). Albumin and apolipoproteins A-I and A-IV are also found in liposomes, but this organelle represents a minor fraction of their total intracellular mass. The liposomal apolipoproteins show varying degrees of association with cisternal lipid and with organelle membranes. Orotic acid may selectively block VLDL production at the level of particle assembly or transorganellar movement. We conclude that liposomal contents probably represent exaggerated accumulations of VLDL assembly intermediates, and that the intracellular partitioning of high density lipoprotein-destined from VLDL-destined components occurs at an early stage in particle biogenesis. Moreover, some unique structural feature of apoB may effect movement of VLDL assembly intermediates through secretory organelles.

Animals