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Biomedical subjects

R W Goy

Publications and source records attributed to R W Goy.

At least 19 recordsLinked to original sources

Neuraxial block for labour analgesia--is the combined spinal epidural (CSE) modality a good alternative to conventional epidural analgesia?

AIM: Apart from conventional epidural analgesia (EA), the combined spinal-epidural (CSE) modality is fast becoming a popular technique for treating labour pain. In this study, we investigated the differences in the patient profile and outcome between CSE and EA for labour pain in KK Women's and Children's Hospital. METHODOLOGY: Data pertaining to 1,532 healthy parturients who had received either CSE or EA for labour pain during a six-month period was systematically collected by using a specially designed form. Multiple logistic regression analysis was used to determine the independent predictors of patient satisfaction and the relation of parturient factors on the choice of block. The side effects and the outcome of labour were also compared. RESULTS: CSE accounted for 80% of all neuraxial blocks performed for labour analgesia (vs 20% for EA). Anaesthesiologists were more inclined to using CSE than EA for multiparous parturients (OR 2.03, p<0.01) in a more painful (OR=1.61, p=0.03) and advanced stage of labour (OR=1.12, p=0.03). The need for supplemental analgesics was greater for EA (p<0.01). Patient satisfaction was higher for CSE (OR=1.77, p<0.026). CSE had a higher risk of pruritus (29% vs 14%, p<0.01) but lower risk of post block neural deficits (0% vs 2%, p<0.01) than EA. No difference in the mode of delivery was detected between the two groups. CONCLUSION: CSE is a safe and good alternative to EA as a technique of neuraxial block for labour analgesia.

Analgesia, Epidural↗

Pulse dye densitometry: a novel bedside monitor of circulating blood volume.

INTRODUCTION: Monitoring of circulating blood volume is important in the management of critically ill patients. Current methods of circulating blood volume measurements such as indicator dilution using radioisotopes or Evans blue dye are unsuitable for clinical application as these tests do not allow for frequent repeated measurements to be done. A direct bedside measurement of circulating blood volume using the principle of pulse dye densitometry was recently introduced. This is essentially an indicator dilution technique using indocyanine green combined with the principle of pulse spectrophotometry. METHODS: This paper aims to review this method of circulating blood volume measurement and provide a summary of the published clinical trials that compared its accuracy with the other conventional methods of circulating blood volume measurement, based on a Medline search, spanning the period 1966 to August 2000. RESULTS: Published studies show that pulse dye densitometry gives comparable results when compared to other conventional methods of blood volume measurement. Its ability to measure circulating blood volume accurately and repeatedly, as frequently as every 20 min makes it suitable for clinical application. CONCLUSION: Pulse dye densitometry provides for a rapid, semi-noninvasive and convenient bedside assessment of circulating blood volume that is applicable clinically. Further studies are needed to ascertain the impact of the use of pulse dye densitometry on the mortality and morbidity of the critically ill.

Blood Circulation↗

Prenatal exposure of female rhesus monkeys to testosterone propionate increases serum luteinizing hormone levels in adulthood.

OBJECTIVE: To determine whether prenatal androgenization of the developing primate hypothalamohypophyseal unit induces irreversible changes in LH secretion. DESIGN: Prospective nonrandomized study. SETTING: An academic research environment. ANIMALS: Forty-one adult ovulatory female rhesus monkeys. INTERVENTION(S): Seventeen female rhesus monkeys exposed prenatally to testosterone propionate (female pseudohermaphrodites) and 24 normal females underwent blood sampling over two ovulatory menstrual cycles. MAIN OUTCOME MEASURE(S): Serum FSH, LH, E2, and T were determined by RIA; P was determined by enzyme immunoassay. Serum bioactive LH was measured by mouse Leydig cell bioassay. RESULT(S): Tonic immunoactive LH hypersecretion and normal FSH release occurred in female pseudohermaphrodites compared with normal females. Periovulatory immunoactive LH and FSH secretion was similar in both female types, whereas a relative increase in the amount of circulating bioactive LH to immunoactive LH was found at midcycle in female pseudohermaphrodites versus normal females. The length of the follicular phase was unaffected by prenatal androgen exposure, but the slopes of serum T and E2 concentrations versus follicular phase cycle day were significantly lower in female pseudohermaphrodites than normal females. Luteal phase length and P secretion were comparable in both types of females. CONCLUSION(S): Androgen exposure during primate neural differentiation may alter permanently the pattern of LH secretion in the presence of cyclic gonadotropin release.

Animals↗

The effects of diethylstilbestrol (DES) before birth on the development of masculine behavior in juvenile female rhesus monkeys.

Eight pregnant rhesus monkeys were injected with 100 microg diethylstilbestrol dipropionate (DESDP) from the 40th day of gestation until term, a long-term treatment. Male (n = 3) and female (n = 5) offspring were obtained. Five other pregnant females were injected with DESDP beginning on the 115th day of gestation and continuing until either the 140th day or term--a relatively short-term treatment. Five female infants were obtained from these short-term treatments. Monkeys from the treated pregnancies were assigned randomly to mother-infant social groups containing untreated male and female infants the same age. They were observed in their peer groups each weekday from 3 to 12 months of age, and the display of mounting and play behavior was recorded for each subject. Results showed that DESDP significantly increased the frequency of display of these juvenile behaviors only in long-term-treated females. However, one of the aspects of mounting that is characteristic of males (the ratio of complete to abortive mounts) was unaffected even by the long-term treatment. Thus, DESDP-treated females displayed a limited behavioral masculinization. Whether this limitation was due to dosage and/or timing or to a selective action of DESDP was not determined. DESDP-treated males were not altered in any measurable way compared to untreated males.

Animals↗

Idazoxan decreases estrogen-induced lordosis in female but not "hormone-independent" lordosis in male guinea pigs of an inbred strain.

This experiment examined whether the imidazoline idazoxan (which binds to alpha-noradrenergic receptors and to imidazoline-preferring sites) interferes with hormone-dependent or hormone-independent lordosis responses. Ovariectomized (ovx) Strain 2 female guinea pigs which were sexually receptive after receiving estradiol benzoate (EB; 3 micrograms/d for 3 days) were injected with either idazoxan (10 mg/kg) or with vehicle at 24 hr after the last EB injection. Idazoxan significantly decreased EB-facilitated lordosis responses in these females. Castrated Strain 2 males, which show lordosis behavior without gonadal hormone administration, were injected with the same dosage of idazoxan (10 mg/kg) or with vehicle. Idazoxan did not inhibit lordosis behavior in these males.

Adrenergic alpha-Antagonists↗

In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin. 2. Effects on sexual behavior and the regulation of luteinizing hormone secretion in adulthood.

When administered to postpubescent male rats, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) decreases plasma androgen concentrations. If such an androgenic deficiency were produced prenatally and/or early postnatally it could impair sexual differentiation of the central nervous system (CNS) and thereby alter male reproductive function. To examine this possibility, sexually dimorphic functions were assessed in male rats born to dams given TCDD (0.064, 0.16, 0.40, and 1.0 micrograms/kg, po) or vehicle on Day 15 of gestation. Masculine sexual behavior was assessed at approximately 60, 75, and 115 days of age. When TCDD-exposed males were caged with receptive control females their mount, intromission, and ejaculation latencies were far longer than normal; these effects were dose-related and were statistically significant at maternal doses as low as 0.16, 0.064, and 0.16 micrograms TCDD/kg, respectively. The numbers of mounts and intromissions to ejaculation were slightly increased by TCDD, while copulatory rates [(mounts+intromissions)/min] were significantly decreased at the three highest maternal doses. Except for a modest increase at the higher doses, TCDD had little effect on the postejaculatory interval. Following assessment of their masculine sexual behavior, the males were castrated and 6 weeks later tested for feminine sexual behavior (lordosis). After being primed with estradiol benzoate and treated with progesterone, males displayed dose-related increases in lordosis quotient and lordosis intensity in response to being mounted by another male. These effects were statistically significant at maternal doses as low as 0.16 and 0.40 micrograms TCDD/kg, respectively. To determine if perinatal TCDD exposure alters the sexually dimorphic regulation of luteinizing hormone (LH) secretion, the LH secretory responsiveness of the hypothalamic/pituitary axis to ovarian steroids was assessed. In unexposed, gonadectomized female rats primed with estradiol benzoate, progesterone injection produced a surge in plasma LH concentrations, whereas in similarly treated control males, plasma LH concentrations were unaffected by progesterone. In castrated, estradiol benzoate-primed male rats that were perinatally exposed to TCDD, progesterone treatment produced dose-related increases in plasma LH concentrations that were statistically significant at the two highest maternal doses. We conclude that in utero and lactational exposure to small amounts of TCDD demasculinizes and feminizes male rats. These effects cannot be accounted for by TCDD-induced hypophagia, modest reductions in adult plasma androgen concentrations, possible nonspecific changes in motor activity, or possible reductions in penile sensitivity to sexual stimulation. The altered sexual behaviors and LH secretion were observed when nearly all TCDD had been excreted (as evidenced by uninduced hepatic ethoxyresorufin-O-deethylase activity).(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Effects of prenatal antiandrogen treatment on masculinization and defeminization of guinea pigs.

Gonadectomized (gdx) guinea pigs which had received the antiandrogen flutamide prenatally were tested for female-typical and male-typical sexual behavior in adulthood. In tests for lordosis behavior, gdx males and females were injected with estradiol benzoate and progesterone. Prenatally flutamide-treated females showed a longer mean lordosis response than control females. This was true whether they were given either a high or a low dose of EB. No male ever showed a lordosis response. In tests for male-typical sexual behavior, gdx adult males were treated with testosterone propionate and tested with stimulus females. The prenatally flutamide-treated males showed significantly decreased levels of ejaculation, a lower intromission rate and a decreased percentage of mounts which included pelvic thrusts, when compared to control males. Mount rate and rate of pericopulatory behavior did not differ between the flutamide and control males. The fact that prenatal administration of flutamide increased female-typical behavior in adult females suggests that the female guinea pig is normally partially defeminized by androgens in utero. The male guinea pig appears to be resilient to attempts to block defeminization with prenatal antiandrogens. However, some aspects of masculinization can be blocked.

Androgen Antagonists↗

Alpha 1 noradrenergic antagonism decreases hormonally-induced and hormonally-independent lordosis.

Manipulations of the alpha noradrenergic (NE) system affect both lordosis and the concentration of hypothalamic steroid receptors. The present studies explored whether NE affects lordosis in guinea pigs via changes in hypothalamic estrogen or progestin receptors or through some other mechanism. The alpha 1 NE antagonist prazosin blocked lordosis which was induced with estradiol benzoate (EB) followed by progesterone (P), lordosis which was induced by EB alone and lordosis which is not dependent upon gonadal hormones for its display. These results suggest that NE modulation of lordosis in the guinea pig is not exerted solely through progestin receptors or estrogen receptors. Because prazosin blocked hormonally-independent lordosis, it is apparent that the NE system modulates some nonhormonal component of lordosis in guinea pigs.

Animals↗

5 alpha-reductase, aromatase, and androgen receptor levels in the monkey brain during fetal development.

To elucidate the metabolic fate and possible role of androgens and their derivatives during primate fetal development, aromatase (AROM), 5 alpha-reductase (5 alpha R), and androgen receptor (AR; cytosolic) levels were assessed in the brain, heart (HRT), lung (LNG), and skeletal muscle (MUS) of fetal rhesus monkeys. Analyses were performed on tissues taken on days 100 and 160 postconception. Five male and four or five female fetuses were examined at each stage. Brain tissues analyzed included medial basal hypothalamus (MBH), amygdala (AMG), cerebellum (CB), corpus callosum (CAL; splenial region), cerebral cortex (CTX), and cingulate cortex (CNG). In the following, enzyme activities are reported as picomoles per mg protein/h, while receptor levels are femtomoles per mg protein. 5 alpha R activity was measurable in all tissues. Analysis of variance revealed significant tissue differences [P less than 0.001, combined stages and sexes; CAL (2.05) greater than MBH (1.08) greater than AMG (0.63) greater than CB (0.4)-CNG-CTX-LNG-HRT-MUS (0.02); -indicates not significantly different]. A significant age x tissue interaction (P less than 0.001) was noted which could be explained by higher MBH and CAL levels in older vs. younger fetuses and higher AMG levels in younger vs. older fetuses. There was also a significant sex x tissue interaction which was attributed to higher female values in the MBH and CAL. AROM activity was detected in all tissues. Levels varied significantly among tissues [P less than 0.001, combined stages and sexes; MBH (0.80)-AMG (0.76) greater than CAL (0.4)-CNG-CB-CTX-LNG-HRT-MUS (0.07)]. Significant age (P less than 0.001) and age x tissue (P less than 0.001) effects were noted, which were due to higher MBH and AMG levels in younger vs. older fetuses. No sex difference in AROM levels was evident in any tissue. AR was measurable in all cases. Although stage and sex differences were not significant, tissue levels varied significantly [P less than 0.001; LNG (2.8)-MUS (2.6)-MBH (2.2) greater than HRT-AMG-CB-CTX-CAL-CNG (0.9)]. These findings indicate that neural and nonneural fetal primate tissues have the potential for transforming androgens to products that could have greater or lesser biological activity. AR were also noted through which dihydrotestosterone or testosterone could effect a genomic response. Since stage, tissue, and sex differences were evident in neural tissues, metabolic and receptor activities may be important for the normal differentiation of sexually dimorphic behavioral systems in monkeys as well as for potential teratogenic changes under abnormal metabolic or physiological conditions.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Obesity in male and female rhesus monkeys: fat distribution, glucoregulation, and serum androgen levels.

Obese (n = 8) and nonobese (n = 6) adult rhesus monkeys (Macaca mulatta) were assessed in terms of body size and distribution of body fat, glucose tolerance, and serum lipid, insulin, and androgen levels. The weights of the obese monkeys were more than 2 SD above the mean for their sex, while the nonobese monkeys averaged less than 0.25 SD from the mean. Obese males and females had excess body fat located predominantly in the abdominal region; abdominal circumference was highly correlated with total body fat, as estimated by the isotope dilution method (r = 0.98; P less than 0.001). Obese monkeys of both sexes had fasting hyperinsulinemia, greater insulin response to iv glucose administration, and marginally impaired glucose tolerance. Obese males had delayed maximal insulin response to glucose administration. Fasting serum triglycerides also were elevated in the obese monkeys (0.95 +/- 0.08 vs. 0.47 +/- 0.05 mmol/L; P less than 0.001). Obese males had lower serum dihydrotestosterone levels than nonobese males (3.1 +/- 0.7 vs. 5.6 +/- 0.4 nmol/L; P less than 0.01). Nonobese females had approximately 2-fold higher serum dehydroepiandrosterone sulfate levels than the other groups. We conclude that obese male and female rhesus monkeys have patterns of fat distribution and glucoregulatory abnormalities similar to those of humans with upper body obesity. The contribution of differences in androgen metabolism to the development of obesity and its complications in rhesus monkeys remain to be defined.

Adipose Tissue↗

The effects of isosexual rearing on adult sexual behavior in captive male rhesus macaques.

The sexual competence of males reared only with other males (isosexually reared) was compared to the sexual competence of males reared in mixed-sex peer groups (heterosexually reared). All subjects were pair-tested with the same 11 females. Isosexually reared males tended to be less sexually active than heterosexually reared males, but the differences were not pronounced. Heterosexually reared males took less time to ejaculate than isosexually reared males, but their ejaculatory frequencies were comparable. Among one peer group of isosexually reared males, their level of sexual competence conformed with their dominance ranks when immature. These results suggest that growing up with female peers is not a prerequisite for the expression of adult sexual behavior among male rhesus macaques and that adult male sexual behavior may be influenced by relative dominance status when immature.

Animals↗

Sex differences in the inhibition by ATD of testosterone-activated mounting behavior in guinea pigs.

Adult male and female guinea pigs from a genetically heterogeneous stock were gonadectomized and tested for mounting behavior before and during various treatments with testosterone cypionate (TC) alone or in combination with an aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD). ATD was implanted subdermally in Silastic capsules (either 1 or 2 in females; 2 or 3 in males). In females 2 capsules of ATD completely blocked the behavioral effects of TC, and 1 capsule was an effective blocker in 58% of the females. The blocking effect was reversed by injection of diethylstilbestrol. In males, there was no measurable effect of ATD on mounting activity even when 3 capsules were implanted. Moreover, the TC induction of higher components of male sexual behavior (intromission and ejaculation) was also not impaired by ATD. Results are interpreted as indicating that either the process of male sexual differentiation or the male genotype eliminates the requirement for aromatization in androgenic activation of sexual behavior.

Androstatrienes↗

Behavioral masculinization is independent of genital masculinization in prenatally androgenized female rhesus macaques.

Genetic female fetuses were exposed transplacentally to testosterone propionate injected into their mothers either early (Days 40 through 64) or late (Days 115 through 139) in gestation. Early and late androgenized females (EAFs and LAFs, respectively) were raised with normal males and females that served as criteria for evaluating degree of behavioral masculinization induced by the prenatal androgen. EAFs were genitally virilized and LAFs were not. Males and untreated females differed reliably on five behavioral measures: males showed more mother-mounting, more peer-mounting, more rough play with peers, a preference for initiating play with male partners, and less grooming of mothers. Neither type of prenatally androgenized female showed masculinization of all five types of behavior. Compared with females, EAFs showed more mother-mounting, more peer-mounting, less mother-grooming, did not differ from females in rough play, and did not manifest a preference for male partners. LAFs, like females, groomed but did not mount their mothers, and did not show a preference for male partners; but unlike females they showed elevated rough play and mounting with peers. EAFs showed a statistically significant delay in puberty onset (menarche), but LAFs did not. Mothers inspected genitalia of their offspring more often if they were males than if they were females. Mothers of EAFs inspected their offspring's genitalia as often as mothers of males, but mothers of LAFs did not. No aspect of maternal behavior was associated with either the amount or kind of masculine behavior shown toward peers. We interpret the results to mean that genital virilization is independent of, and largely irrelevant to, the expression of those behavioral traits that characterize the juvenile male social role. Moreover, the individual behavior traits that are components of the juvenile male role are independently regulated by the organizing actions of androgen and have separable critical periods. Of the two major traits, mounting peers and rough play with peers, the latter has a greater requirement for androgenic stimulation late in prenatal life.

Aggression↗

Social and hormonal influences on behavior of adult male, female, and pseudohermaphroditic rhesus monkeys.

We previously demonstrated that in a simple pair test situation the expression of adult male sexual behavior by rhesus monkeys depends on both prenatal (organizational) and adult (activational) androgen exposure. In the present study we used a more complex social situation (trio tests) to evaluate the behavior of males, females, and female pseudohermaphrodites. In these trio tests, the experimental subjects were tested with two estrogenized stimulus females simultaneously. Sex differences in behavior were made apparent by this complex testing situation that could not have emerged in the pair test. Gonadectomized males and female pseudohermaphrodites, but not ovariectomized females that were concurrently receiving TP, exhibited increased male sexual behavior in trio tests compared to pair tests. In trio tests, the males and pseudohermaphrodites showed evidence of partner preference by interacting almost exclusively with one of the two stimulus females. These "preferred females" in turn were responsible for the majority of the proceptive behavior exhibited in these tests. Ovariectomized females rarely displayed male sexual behavior in either test situation. These results further support the hypothesis that prenatal androgen exposure predisposes monkeys to exhibit masculine behavior traits when they reach adulthood and are exposed to the activational influences of androgens.

Agonistic Behavior↗

Androgenic influences on body size and composition of adult rhesus monkeys.

The effects of daily treatment with testosterone propionate (TP, 2 mg/kg) and dihydrotestosterone propionate (DHTP, 2 mg/kg) were examined in rhesus monkeys in three experiments. In experiments 1 and 2, males and females gonadectomized in infancy, and female pseudohermaphrodites produced by prenatal exposure to TP or DHTP and gonadectomized postpubertally, were studied in conjunction with intact males (IM). The IM group was heavier in adulthood than the three gonadectomized groups, which did not differ in body weight from each other. Genetic males had greater crown-rump length than genetic females. Treatment of the gonadectomized groups with TP produced large increases in body mass (averaging approximately 50%) that were attributable to accretion of lean tissue. This effect did not differ significantly between males and females. In experiment 3, additional groups of males that had been castrated as infants were given daily injections with DHTP or oil. The DHTP treatment resulted in increases in body size that were not different from those seen following TP treatment. When TP and DHPT treatments were discontinued, body weights and dimensions reverted to base-line values. Increased body size induced by TP and DHTP was accomplished without reliable increases in food intake. Because testosterone (T) is metabolized to dihydrotestosterone (DHT), while DHT cannot be converted to T, these results show that both T and DHT are effective anabolic hormones in rhesus.

Aging↗

Estrogenic contributions to sexual differentiation in the female guinea pig: influences of diethylstilbestrol and tamoxifen on neural, behavioral, and ovarian development.

We administered the synthetic estrogen, diethylstilbestrol (DES), or the antiestrogen, tamoxifen, to pregnant guinea pigs and observed the consequences for sexual differentiation of their female offspring. Hormones were administered during the period when treatment of fetuses with testosterone influences the development of sex-related traits (approximately Days 30 to 65 of gestation). Ovarian function, masculine and feminine sexual behavior, and the structure of a sexually dimorphic neural region in the preoptic area were assessed in adulthood in hormone-exposed animals and in oil-treated and untreated controls. Prenatal exposure to DES dipropionate (DESDP) caused masculinization and defeminization. DESDP-treated females mounted more than control females, both without hormonal stimulation and when given testosterone propionate (TP) as adults. The sexually dimorphic neural region was also masculinized in these females. In regard to defeminization, they showed delayed vaginal opening, impaired progesterone (P) production, an absence of corpora lutea, and impaired lordosis and mounting responses to estradiol benzoate (EB) and P. Prenatal treatment with tamoxifen produced a complicated pattern of results. Tamoxifen-exposed females evidenced less masculine-typical behavior, showing diminished mounting without hormonal stimulation and in response to TP. However, they also showed delayed vaginal opening, enhanced P production, and impaired mounting in response to EB and P. Their lordosis behavior and the volume of the sexually dimorphic neural region were unaffected. These results suggest that estrogens play a substantial role in sexual differentiation in the guinea pig. High levels of estrogen promote masculine-typical development, and unusually low levels may impair some aspects of both masculine-typical and feminine-typical development.

Animals↗

Lordosis behavior in males of two inbred strains of guinea pig.

The lordosis behavior of male guinea pigs from inbred strains 2 and 13 was examined. Significantly more isolated gonadally intact males of strain 2 than strain 13 displayed lordosis. Castration did not decrease the display of lordosis. In castrated strain 2 males, those which showed lordosis did not have higher plasma androgen, estrone or estradiol levels than those which did not show lordosis. They also did not differ hormonally from ovariectomized strain 2 females even though strain 2 females never showed lordosis without hormone replacement. Although the lordosis shown by strain 2 males was not related to endogenous gonadal hormone levels, estradiol benzoate (EB) administration facilitated lordosis. EB had no clear effect on lordosis in strain 13 males. Progesterone after EB priming had no further facilitative effect in males of either strain. These results indicate that lordosis is more readily elicited from strain 2 than strain 13 males. Furthermore, lordosis in strain 2 males is not dependent upon gonadal hormones for its display although it is facilitated by EB (but not progesterone).

Animals↗