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Background: The GlideScope (Verathon Inc., Bothell, WA, USA) and Airway Scope (Hoya Corp., Tokyo, Japan) have both been used for difficult airway management, including in patients with cervical spine pathology. The Airway Scope's disposable blade has a tube channel to guide tracheal tube insertion through the glottis. Our hypothesis is that this tube guidance system improves the ease of tracheal intubation compared with the GlideScope, which does not have a tube guiding system. We tested this hypothesis in a randomized comparison of the two videolaryngoscopes in patients whose cervical spines were immobilized.Methods: Seventy consenting patients were randomized to have tracheal intubation with the GlideScope (n=35) or the Airway Scope (n=35). In all patients, we applied manual in-line stabilization of the cervical spine throughout airway management. All the airway procedures were carried out by two anaesthetists experienced in the use of both videolaryngoscopes.Results: The tracheal intubation time was 34.2 (sd 25.1) s with the Airway Scope compared with 71.9 (47.9) s with the GlideScope (P<0.001). Tracheal intubation was successful with the Airway Scope in 35 (100%) patients compared with 31 (88.6%) patients with the GlideScope (P=0.114). Tracheal intubation was successful within 60 s in 33 (94.3%) patients with the Airway Scope and 22 (62.9%) patients with the GlideScope (P=0.003).Conclusions: These results suggest that the Airway Scope's tube guide system enables more rapid tracheal intubation compared with the GlideScope in patients with cervical spine immobilization. [ABSTRACT FROM AUTHOR]

BACKGROUND: The LMA CTrach system (The Laryngeal Mask Company, Singapore) is a development of the LMA Fastrach system (The Laryngeal Mask Company, Singapore), with integrated fiberoptic bundles and a detachable liquid crystal display viewer. This randomized study of 271 patients compared tracheal intubation with these two systems. METHODS: In both groups, ventilation was optimized after insertion of the laryngeal mask conduit before proceeding further: intubation with the LMA Fastrach, and optimizing the conduit placement and view and then intubation with the LMA CTrach. The first-attempt and overall success rates of tracheal intubation, and the times required, were recorded. RESULTS: Tracheal intubation was successful on the first attempt in 93.3% of patients with the LMA CTrach and 67.9% of patients with the LMA Fastrach (P < 0.001). The success rates within three attempts were 100% with the LMA CTrach and 96.4% with the LMA Fastrach (P = 0.06). The median (interquartile range) time for the complete tracheal intubation process was 116 (82-156) s with the LMA CTrachand 100 (74-121) s with the LMA Fastrach (P = 0.002). There was no correlation between the grade of conventional laryngoscopy and success of intubation with either system. CONCLUSIONS: The ability to view the glottis and optimize placement of the LMA CTrach under vision enabled a higher first-attempt success rate of tracheal intubation with the LMA CTrach. However, more time is required with the LMA CTrach, there are failed views in some patients, and its cost effectiveness remains unclear. [ABSTRACT FROM AUTHOR]

The obesity epidemic continues to increase, with half of US women predicted to be obese by 2030. Women with obesity are at increased risk for not only cardiovascular and liver disease, but also reproductive disorders. Although mouse models are useful in studying the effects of obesity, there is inconsistency in obesity-induction methods, diet composition, and mouse strains, and studies using female mice are limited. In this study, we sought to compare the effects of a 45% high-fat diet (HFD) versus a 60% HFD on the uterine estrous cycle of nulligravid C57BL/6J mice. For 22 weeks, we placed a total of 20 mice on either a 60% HFD, 45% HFD, or each HFD-matched control diet (CD). Both HFDs produced significant weight gain, with 60% HFD and 45% HFD gaining significant weight after 2 weeks and 15 weeks, respectively. Additionally, both HFDs led to glucose intolerance, fatty liver, and adipocyte hypertrophy. Mice fed 60% HFD displayed hyperphagia in the first 12 weeks of HFD treatment. Moreover, 60% HFD-treated mice had a longer estrous cycle length and an increased percentage of estrus stage samplings compared to CD-treated mice. Estrous cycle stage-controlled 60% HFD-treated mice displayed an increased estrogen-to-progesterone ratio and decreased ovarian corpora lutea compared to CD-treated mice, which may underlie the observed estrous cycle differences. There was no significant difference between diets regarding endometrial morphology or the percent of endometrial CD45+ immune cells. Our results indicate that consideration is needed when selecting a HFD-induced obesity mouse model for research involving female reproductive health., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Studies looking at individual variability in cognition have increased in recent years. We followed 43 marmosets (21 males, 22 females) from infancy to young adulthood. At 3-months old, marmosets were trained to touch a rewarded stimulus. At 9-, 15-, and 21-months old, they were given visual discrimination and cognitive bias tests, and urine samples were collected to examine hormone levels. Marmosets were significantly more successful learners at 15 months than 9 months. Individuals who were more successful learners at 9 months were also more successful at 15 months, with more male learners than expected at 15 months. At 9 months, learning success was associated with higher cortisol levels. At 15 months, males with higher estradiol levels were more successful learners, whereas at 21 months, females with higher estradiol and cortisol levels tended to be less successful learners and more pessimistic. Nine months, therefore, appears to be an important developmental timepoint for acquiring cognitive control, which has developed by 15 months. Steroids may have differential effects on each sex, with complex interactions between gonadal and adrenal hormones having an influence on cognitive function over the lifespan. This longitudinal study offers new insight into cognition, including its development and biological underpinnings., (© 2023 Wiley Periodicals LLC.)

Common marmoset fathers are highly involved in care of their infants. However, variability exists in their response to infant behavior even in paternally experienced fathers. Using infant distress cries as a motivation test, we investigated: 1. the differences in paternally experienced fathers' motivation to search for the infant vocalization stimuli; 2. the relationship between a father's motivation to search for the source of the infant cries and testosterone levels; and 3. if there is a rapid steroidogenesis pathway leading to increased testosterone and estradiol in the peripheral circulation. Only 44% of the paternally experienced fathers showed a high frequency of searching for the source of the infant distress cries. Through the use of multisteroid analysis, we found high responsive fathers had significantly higher levels of progesterone and testosterone in response to infant distress cries compared to a control stimulus with progesterone and androstenedione correlating with testosterone, while no differences were seen in low responders. The frequency to search for the infant stimuli was positively correlated with higher testosterone compared to control vocal levels. These results suggest that searching for the source of infant cries represents a motivation behavior for fathers that is activated by testosterone and reflects rapid circulating testosterone., (Published by Elsevier Inc.)

Insulin is a peptide hormone that is secreted by the β cells of the pancreas and is essential to the metabolism of carbohydrates, fats, and proteins in the body. The marmoset insulin peptide is not homologous with human insulin and therefore commonly available assays do not work for this species. Due to the increasing popularity of marmoset research, a simple, specific assay for the quantitation of marmoset insulin is needed. This study aimed to develop and validate a bottom-up proteomic workflow with trypsin digestion and analysis using LC coupled with triple quadrupole mass spectrometry (LC-MS/MS). Marmoset serum proteins were subjected to denaturation, reduction, and enzymatic cleavage to extract a unique, 7 amino acid peptide for quantitation of marmoset insulin. Resolution of the peptide was achieved by LC-MS/MS using electrospray ionization operating in positive mode. Calibration was achieved by aliquot dilution of fully synthetic marmoset insulin tryptic peptide into macaque serum. A stable-isotope labeled ( 13 C, 15 N) synthetic marmoset insulin tryptic peptide was used as internal standard. The assay was fully validated according to bioanalytical method validation guidelines for linearity, precision, and dilution linearity using purified marmoset insulin. The limit of detection was 15.49 pmol/L and the limit of quantitation was 140.78 pmol/L. Biological validation was achieved by comparison of samples previously run by radioimmunoassay and measurement of the marmoset insulin response to glucose via an oral glucose tolerance test (OGTT). The physiological range of marmoset insulin was shown to be 84.5 to 1222 pmol/L. In summary, this paper presents a simple, reproducible method to measure marmoset insulin in serum using LC-MS/MS., (Copyright © 2022 Elsevier B.V. All rights reserved.)

There is currently no consensus about the mean volume of blood lost during spinal tumour surgery and surgery for metastatic spinal disease. We conducted a systematic review of papers published in the English language between 31 January 1992 and 31 January 2012. Only papers that clearly presented blood loss data in spinal surgery for metastatic disease were included. The random effects model was used to obtain the pooled estimate of mean blood loss. We selected 18 papers, including six case series, ten retrospective reviews and two prospective studies. Altogether, there were 760 patients who had undergone spinal tumour surgery and surgery for metastatic spinal disease. The pooled estimate of peri-operative blood loss was 2180 ml (95% confidence interval 1805 to 2554) with catastrophic blood loss as high as 5000 ml, which is rare. Aside from two studies that reported large amounts of mean blood loss (> 5500 ml), the resulting funnel plot suggested an absence of publication bias. This was confirmed by Egger's test, which did not show any small-study effects (p = 0.119). However, there was strong evidence of heterogeneity between studies (I(2) = 90%; p < 0.001). Spinal surgery for metastatic disease is associated with significant blood loss and the possibility of catastrophic blood loss. There is a need to establish standardised methods of calculating and reporting this blood loss. Analysis should include assessment by area of the spine, primary pathology and nature of surgery so that the amount of blood loss can be predicted. Consideration should be given to autotransfusion in these patients.

Context: Simulators provide an effective platform for the learning of clinical motor skills such as endotracheal intubation, although the optimal learning technique remains unidentified. We hypothesised that, for novices, experiential learning would improve the learning and retention of endotracheal intubation compared with guided learning., Methods: Year 4 medical students were randomised to either guided or experiential learning. Students in the guided group were taught using the conventional step-by-step technique. Students in the experiential group had to work out the correct technique for intubation on their own. Both groups had further opportunities to intubate manikins and patients during their postings. The students were recalled 3, 6, 9 and 12 months later, and their intubation skills assessed in four major categories: equipment preparation; intubation technique; successful intubation, and placement confirmation., Results: A total of 210 students (107 guided, 103 experiential) participated in the study. At 3 months, 64.5% of the students in the experiential group successfully intubated the manikin, compared with 36.9% in the guided group (P < 0.001). The experiential group also had higher overall scores, signifying quality of intubation attempts, at 3 months (79% versus 70%; P < 0.001). Success rates and overall scores for both groups were comparable at 6 and 9 months, but were better in the experiential group at 12 months. Success rates improved with time, reaching 86% at 12 months., Conclusions: Novices learned and retained the skill of endotracheal intubation better with experiential learning. This study suggests that experiential learning should be adopted for the teaching of endotracheal intubation and that refresher tuition at 3-monthly intervals will prevent the decay of this skill in infrequent users.

Background: The laryngeal tube has a potential role in patients with a difficult airway, but cricoid pressure is required if the patient is at risk of aspiration. The effect of cricoid pressure on insertion of these devices is unknown., Methods: In a randomized cross-over study, the laryngeal tube (25 patients) or the laryngeal tube-suction II (15 patients) was inserted with cricoid pressure applied on one occasion and with sham pressure on the other occasion. Adequacy of ventilation, time to achieve adequate ventilation, and the leak pressure were assessed., Results: Ventilation was adequate in all patients when sham pressure was applied. Cricoid pressure significantly reduced the rate of adequate ventilation to 6 of 25 patients for the laryngeal tube [P < 0.001; 95% confidence interval (CI) for difference: 59-93%] and to 5 of 15 patients for the laryngeal tube-suction II (P < 0.05; 95% CI for difference: 43-91%). The median time taken to achieve adequate ventilation for the laryngeal tube was 10 s [inter-quartile range (IQR): 8-15] (range 5-26) for sham pressure and 25 s (15-32) (15-33) for cricoid pressure; the median leak pressure was 30 (IQR: 30-30) (range 20-30) cm H2O for sham pressure and 15.5 (14.3-20.5) (12-22) cm H2O for cricoid pressure., Conclusions: Continuous cricoid pressure prevents correct placement of the laryngeal tube and the laryngeal tube-suction II such that placement and ventilation via these devices are ineffective. The effect of cricoid pressure on ventilation via these devices, after correct placement, remains unknown.

Background: The LMA CTrach++ system has integrated fibreoptics to enable viewing of the glottis to aid tracheal intubation via a laryngeal mask conduit. Earlier evaluations of this system had shown high success rates of insertion, ventilation and tracheal intubation, but frequent difficulty or failure to view the glottis., Method: We evaluated CTrach views in 100 patients. In 69 patients with partial or no views of the glottis, we evaluated the causes with the aid of an Olympus LF-DP fibreoptic laryngoscope passed through the CTrach. In those with poor views, we tested the effectiveness of simple corrective measures to improve the views and optimize CTrach placement. These included pushing the CTrach deeper in, partial withdrawal by 6 cm and reinsertion to correct epiglottic downfolding, withdrawal by 1 cm and applying forward lift to correct obstruction by the arytenoids, and complete removal to clean the fibreoptic ports followed by reinsertion when secretions were the problem., Results: Downfolding of the epiglottis caused poor views in 57 patients, which was correctable in 51. Obstruction of the view by the arytenoids occurred in seven patients and by secretions in five, all of which were correctable. With the Ctrach, we were able to ventilate the lungs in all patients, view the glottis in 94 and intubate the trachea in 97 patients., Conclusion: Despite the ability to ventilate the lungs in all patients with the CTrach, poor initial views were very frequent, indicating suboptimal placement, although most poor views can be improved, leading to a high intubation success rate.

Background: The LMA CTrach is a new laryngeal mask system consisting of an LMA CTrach Airway with integrated fibreoptic channels, and a detachable LMA CTrach Viewer. This system enables viewing of the larynx and aids endotracheal intubation through a laryngeal mask airway. Method. We used and evaluated this system in 100 adult patients undergoing general anaesthesia for elective surgery. Our primary outcomes were the success rates of LMA CTrach Airway insertion and endotracheal intubation with this system., Results: We were able to insert the LMA CTrach Airway in and to ventilate all 100 patients. We were successful in endotracheal intubation, either under vision or blind, in 96 patients. We were able to view the larynx in 84 patients, but the quality of the best view obtained was very variable. The median (inter quartile range) time for the complete intubation process was 166 (114-233) s. The system allowed nearly continuous ventilation and oxygenation during the process., Conclusions: The LMA CTrach system has potential advantages over the LMA Fastrach system, including the ability to align the LMA outlet with the larynx and a high first intubation attempt success rate. However, it was difficult to view the larynx with the LMA CTrach compared with direct laryngoscopy, and expectations must be moderated.

The combined spinal-epidural technique (CSE) has been associated with prolonged motor recovery and more frequent arterial hypotension as compared with a single-shot spinal (SSS) technique. We determined the median effective dose (MED) of intrathecal hyperbaric bupivacaine for CSE and SSS by using the up-down sequential allocation technique. Sixty male patients were randomly allocated to receive intrathecal administration through an SSS or CSE technique. Needle insertion occurred at the L3-4 interspace in all patients. In SSS, 9.5 mg of hyperbaric bupivacaine was administered through a 27-gauge Whitacre spinal needle. In CSE, a 17-gauge Tuohy needle with 4 mL of air was used to locate the epidural space, through which a 27-gauge Whitacre spinal needle was introduced and 7.0 mg of hyperbaric bupivacaine was administered. The dosing adjustment was 0.5 mg. A "successful" outcome was arbitrarily defined as sensory anesthesia at or above the T6 dermatome lasting for 60 min. A "success" resulted in a 0.5-mg decrement, whereas a "failure" resulted in a 0.5-mg increment in the next patient. There were 13 successes in both groups. The MED of bupivacaine was 9.18 mg (95% confidence interval, 8.89-9.47 mg) for CSE as compared with 11.37 mg (95% confidence interval, 10.88-11.86 mg) for SSS (P < 0.001). CSE required 19.3% (95% confidence interval, 14.9%-23.6%) less local anesthetic to achieve the defined clinical target. We found significant discrepancies in the MED of hyperbaric bupivacaine between the two techniques. Under similar clinical conditions, a 20% decrement in the dose of bupivacaine may be warranted whenever CSE is intended in place of SSS.

Objective: Machado-Joseph disease is a form of progressive spino-cerebellar ataxia with both bulbar and peripheral neurological manifestations. To date, anesthesia for patients affected by this disease has not been described. General anesthesia may be problematic because of the risk of pulmonary aspiration and hypoxia. We describe our experience with the successful use of combined spinal-epidural in a patient with Machado-Joseph Disease (MJD)., Case Report: A 38-year-old woman with MJD complicated by significant bulbar and peripheral neuropathy presented for an elective vaginal hysterectomy. She had no other medical history of note. After informed consent, subarachnoid block was performed by combined spinal-epidural anesthesia at the L2-3 lumbar intervertebral space with hyperbaric bupivacaine 12 mg, morphine 100 microg, and fentanyl 10 microg. Surgery proceeded uneventfully, with excellent postoperative analgesia. There was full recovery of preinduction neurologic function by the sixth postoperative hour., Conclusions: Central neuraxial anesthesia is an option for patients with MJD presenting for lower abdominal and lower extremity operations. Combined spinal-epidural anesthesia confers hemodynamic stability yet allows for augmentation of intraoperative anesthesia and postoperative analgesia.

Unlabelled: The extent of the intrathecal compartment depends on the balance between cerebrospinal fluid and subatmospheric epidural pressure. Epidural insertion disrupts this relationship, and the full impact of loss-of-resistance on the qualities of subarachnoid block is unknown. In this study we sought to determine if subarachnoid block, induced by combined spinal-epidural (CSE) using loss-of-resistance to air could render higher sensory anesthesia than single-shot spinal (SSS) when an identical mass of intrathecal anesthetic was injected. Sixty patients, scheduled for minor gynecological procedures, were randomly allocated into three groups all receiving 10 mg of 0.5% hyperbaric bupivacaine. In the SSS group, intrathecal administration was through a 27-gauge Whitacre spinal needle inserted at the L3-4 level. For the CSE group, the epidural space was identified with an 18-gauge Tuohy needle using loss-of-resistance to 4 mL of air. After intrathecal administration, a 20-gauge catheter was left in the epidural space. No further drug or saline was administered through the catheter. The procedure was repeated in group CSE ((no-catheter)) except without insertion of a catheter. Sensorimotor anesthesia was assessed at regular 2.5-min intervals until T10 was reached. In all aspects, there was no difference between CSE and CSE ((no-catheter)). Peak sensory level in SSS was lower than CSE and CSE ((no-catheter)) (median T5 [max T3-min T6] versus (T3 [T1-4] and (T3 [T2-5]) (P < 0.01). During the first 10 min postblock, dermatomal thoracic block was the lowest in SSS (P < 0.05). Time for regression of sensory level to T10 was also shortest in SSS. Hypotension, ephedrine use and period of motor recovery were more pronounced in CSE and CSE ((no-catheter)). We conclude that subarachnoid block induced by CSE produces greater sensorimotor anesthesia and prolonged recovery compared with SSS. There is also a more frequent incidence of hypotension and vasoconstrictor use despite using identical doses and baricity of local anesthetic., Implications: This study confirms that induction of subarachnoid block by a combined-spinal epidural technique produces a greater sensorimotor anesthesia and results in prolonged recovery when compared with a single-shot spinal technique. There is a more frequent incidence of hypotension and vasoconstrictor administration despite identical doses of intrathecally administered local anesthetic.

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.

Background: EMLA cream is the current technique of choice to reduce pain during venous cannulation in most paediatric practice. Its use is limited by logistic arrangements and failure to improve cooperation and allay anxiety. Nitrous oxide (N2O) would appear to be an effective alternative. A combination technique may be useful in selected patients., Methods: One hundred and twenty unpremedicated ASA 1 and 2 day surgery patients, aged 8-15 years were randomized into group 1 (EMLA + air/O2), group 2 (50% N2O/50% O2) and group 3 (EMLA + 50% N2O/50% O2). All patients underwent cannulation on the dorsum of the hand with a 22-G intravenous catheter. Pain behaviour before cannulation was assessed by an observer with Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). Pain during cannulation was evaluated with CHEOPS by an observer and Visual Analogue Scale (VAS) (0-100 mm) by the patient. Satisfaction score (0-100%) for the experience were reported by the patient. Degree of ease of cannulation, time for cannulation were assessed. Heart rate, oxygen saturation were compared before, during and after cannulation., Results: The self-reported VAS for group 3 (10.10 +/- 14.99) was significantly lower than group 1 (26.13 +/- 27.59) and group 2 (18.35 +/- 18.11) (P = 0.003). No significant difference existed between VAS for group 1 and 2. There were also significantly more patients with VAS = 0 in group 3 (23/40) versus group 2 (11/40) versus group 1 (10/40), P = 0.004. The satisfactory score in group 3 (93 +/- 9.96) was significantly higher (P = 0.039) than group 1 (81.13 +/- 24.61) and group 2 (84 +/- 22.02). The increase in CHEOPS from before to during cannulation was significant only in group 1 (P = 0.002). There was no significant difference between frequency of patients with side-effects, ease of cannulation and time taken for cannulation in the three groups., Conclusions: EMLA and 50% N2O are equally effective for pain reduction while a combination technique provides superior analgesia and satisfaction. N2O has an advantage over EMLA in reduction of pain related behaviour in older children.

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.

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.

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.

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.

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)

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.

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.

Specific brain regions, namely, thalamus, tectum, tegmentum, cerebellum, medulla and pineal, from five proestrous rats were incubated for 30 min with [3H]progesterone. After reverse isotopic dilution analysis, the following metabolites were identified in all incubations by purification to constant specific activity, derivative formation and/or gas liquid chromatography trapping: [3H]5alpha-pregnane-3, 20-dione (10-20% of the starting substrate except pineal -- 0.7%), [3H]3alpha-hydroxy-5alpha-pregnan-20-one (1.6-3.8% except for pineal -- 0.5%) and [3H]20alpha-hydroxy-4-pregnen-3-one (0.05-0.11%). Preliminary results from the corpus collosum incubation indicated the presence of the same metabolites. Although some apparent constant specific activities were obtained for 20alpha-hydroxy-5alpha-pregnan-3-one and 5beta-pregnane-3, 20-dione, the low levels of 3H associated with these steroids did not permit a definitive identification. The results indicate the presence of at least delta1-steroid 5alpha-reductase, 3alpha-hydroxysteroid dehydrogenase and 20alpha-hydroxysteroid dehydrogenase activities with progesterone as substrate in the brain regions examined.

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.

Urine was collected from 6 female cotton-top tamarins (Saguinus o. oedipus) and urinary oestrone and oestradiol concentrations were measured by radioimmunoassay. Oestrone was excreted at 50-fold higher concentrations than oestradiol. Five females showed patterns of regular oestrone cyclicity, with a mean peak-to-peak oestrone cycle of 23.6 +/- 1.2 days. Levels of oestradiol tended to vary with levels of oestrone excretion, but peaks were less pronounced and more variable. The sixth female, diagnosed as having 'wasting marmoset syndrome', had very low levels of excreted oestrogens, suggesting infertility. We suggest that urinary oestrone provides a good index to ovarian cyclicity in female cotton-top tamarins.

Bilateral radiofrequency lesions were made in the medial preoptic-anterior hypothalamic (MP-AH) area of 6 adult male rhesus monkeys; 5 sham-lesioned subjects served as controls. Behavioral analysis consisted of observations on copulatory behavior, yawning, masturbation and some aspects of social behavior. MP-AH lesions reduced or completely eliminated the display of manual contacts of the partner, mounts, intromissions and ejaculations without interfering with masturbation. Yawning, a sexually dimorphic behavior, was not affected either, Measure of several social behaviors indicated no evidence of social withdrawal or other aberrance of social interactions, which might have led to the decline in heterosexual behavior. The results with regard to copulatory behavior were consistent with the effects of MP-AH lesions in rats, cats and dogs. In rhesus monkeys it appears as though the MP-AH region is specifically involved in the mediation of heterosexual copulation and is not vital to the performance of other forms of male sexual activity such as masturbation. Also the MP-AH is not critical for the display of all sexually dimorphic behaviors. The types of behavioral change in MP-AH lesioned subjects differed to some extent from those following castration, indicating that the effects of the lesions cannot be explained as basically that of functional castration.

Competitions for access to water were conducted weekly in a captive group of Macaca arctoides. After giving birth, parturient females that had been low in order of access showed elevation. Elevation was not due solely to increased motivation for water, since it depended on the presence of higher ranking animals. Presence of higher ranking animals did not influence agonistic behavior involving parturient females as greatly as it influenced order of access to water. Elevation of access order after parturition tended to be long lasting, and it was not an artifact of depression in access order preceding birth. Delivery of a dead fetus did not alter access order.

In the female guinea pig, copulation produces a rapid inhibition of subsequent sexual receptivity. Injection of the alpha adrenergic agonist clonidine before mating blocked the early inhibitory effects of coital stimulation, while the serotonergic antagonist methysergide, and the dopaminergic antagonist pimozide were without effect. The effects of clonidine were prevented by pretreatment with the alpha adrenergic antagonist yohimbine. These results suggest that an adrenergic system is involved in the copulation-induced inhibition of receptivity and provide further evidence that such a system has an important facilitative role in the control of female sexual behavior in the guinea pig.

Negative feedback regulation of LH release was studied by ovariectomy and estrogen treatment in female guinea pigs of four different ages (days 10, 30, 50, and 150). The average age at first ovulation in guinea pigs in our colony was 60.1 +/- 2.2 days (n = 33). Bilateral ovariectomy (OVX) on day 30, 50, or 150 of age resulted in a sharp increase in serum LH concentrations within 3 days, and this rise continued for 9 days, when LH values reached a plateau. In contrast, when OVX was performed on day 10 of age, only a slight elevation in LH levels was observed during the first 16 days after surgery. Twenty days after OVX (day 30 of age), LH concentrations started to increase rapidly and reached the maximum value on day 38 of age; this latter response was similar to that observed immediately after OVX in animals in the three older age groups. Serum LH concentrations after LHRH administration (2 micrograms/kg BW) were similar in ovariectomized females on days 23 and 43 of age, suggesting that the postcastration increase in LH secretion after day 26 of age was not due to a change in pituitary sensitivity. Daily injections of estradiol benzoate at doses of 0.5 and 2.0 micrograms/kg BW from 15-20 days after OVX suppressed LH levels in all four age groups. The present findings indicate that an increase in the capacity for LH release occurs around day 30 in the female guinea pig. Since this increased LH release is not due to an apparent change in pituitary sensitivity to LHRH, the endogenous release of LHRH may be inhibited before day 30 of age. These results suggest that an alteration in the regulation of LH release by the brain may occur before the onset of puberty in female guinea pigs.

Neural tissues from adult, castrated male guinea pigs were examined for their capability to concentrate and metabolize [1,2-3H]testosterone (T) and [1,2-3H]dihydrotestosterone (DHT), both in vitro and in vivo. In vitro uptake of DHT and T was greater in the hypothalamus and anterior pituitary than in the cerebral cortex. With DHT as the substrate, the 800 times g particulate concentration of this compound was highest in the hypothalamus, although in this tissue, particulate concentration was less than that of the cytoplasm. In the cerebral cortex 5alpha-androstane-3,17-dione was the most abundant metabolite, whereas 5alpha-androstane-3,17-dione, 5alpha-androstane-3alpha,17beta-diol, and 5alpha-androstane-3beta,17beta-diol were all present in equivalent amounts in the hypothalamus and pituitary. Incubation with T resulted in the formation of DHT, 4-androstene-3,17-dione, and a compound with the mobility of 5alpha-(or 5beta-)androstane-3,17-dione. The radioactivity associated with DHT was the most prevalent in the pituitary (1.3%), and least prevalent in the cerebral cortex (0.6%), and in all cases cytoplasmic concentration of this compound exceeded the concentration in the particulate fraction. Recrystallization failed to confirm the presence of estradiol-17beta. Although there were no apparent tissue differences in the uptake of DHT or T 1 hour after their injection, intracellular distribution varied. In all tissues examined, that percentage of total radioactivity attributable to DHT was greatest in the 800 times g particulate preparations, particularly in the hypothalamus. Thus neural tissues in the guinea pig, as in other species, exhibit differential uptake and metabolism of androgen through which physiological and behavioral effects may be mediated.

Behavioural and hormonal data were collected throughout pregnancy in captive rhesus monkeys. Heterosexual pairs observed in daily time-limited mating tests showed two distinct periods of increased sexual interaction, as measured by the incidence of ejaculation. One period was coincident with the preovulatory oestradiol peak, while the other occurred between the 6th and 10th weeks of pregnancy. The positive relationship found during the menstrual cycle between the ratio of circulating oestradiol: progesterone and degree of sexual activity continued for the first 8 weeks of pregnancy. However, sexual activity ceased in the second half of pregnancy despite a continued high oestradiol: progesterone ratio.

The effects of ventromedial hypothalamic (VMH) lesions on body weight, body composition, and food intake were examined in gonadally intact and gonadectomized adult rats of both sexes. The most striking finding was that, while gonadectomy only modestly augmented the weight gain following VMH lesions in females, castrated VMH males gained twice as much weight as gonadally intact VMH males. Furthermore, the weight gain of the castrated VMH males was comparable to that seen in VMH females. Thus, castration of males eliminates the sex difference in body weight gain that is ordinarily observed in gonadally intact animals following VMH lesions. The degree of weight gain in all VMH animals correlated highly with the amount of food eaten, and additional body weight of all VMH animals was accounted for by increased body fat.

Brain serotonin (5-HT) levels and accumulation rate within the dorsal raphe nucleus (DR) were elevated in ovariectomized (OVX) rats after ovarian steroid treatment, which consisted of estradiol benzoate (EB) followed by progesterone (P) 48 hr later. Some animals were also given the monoamine oxidase (MAO) inhibitor pargyline at designated times 10-40 min prior to sacrifice. Decapitation occurred 5 hr following the second steroid injection and 4-6 hr into the dark phase of a 14:10 light/dark cycle. Basal 5-HT levels and the rate of 5-HT accumulation (5-HTr) following MAO inhibition were estimated by radioenzymatic assay of brain tissue punched from frozen sections or dissected freehand. Within the DR, 5-HT levels and 5-HTr rates were respectively 13.8% (p less than 0.001) and 23.2% (p less than 0.025) higher in EB+P treated females compared with oil controls. Differences in basal 5-HT were found within the median raphe nucleus, but these were inconsistent from experiment to experiment. No differences were found in tissue immediately adjacent to these nuclear regions or within other brain regions including the ventral medial nucleus and suprachiasmatic nucleus of the hypothalamus. Increased levels of 5-HT were also found in grossly dissected tissue containing the mesencephalic raphe nuclei.

Influences of estrogens on the differentiation of psychosexual traits in the female guinea pig were studied. Pregnant animals were injected intramuscularly with either 1, 2, or 3.3 micrograms estradiol benzoate (EB) or with 1 or 3 micrograms diethylstilbestrol dipropionate (DESDP). Injections were started on the 29th day of pregnancy, given daily for 6 days, and continued every other day until parturition. Female offspring were evaluated for onset of puberty, ovarian function, and lordosis and mounting behavior in adulthood. Prenatal treatment with 3 micrograms DESDP caused delayed puberty, impaired ovarian function, reduced responsiveness of lordosis to EB and P in adulthood (defeminization), augmented mounting in the absence of hormones (masculinization), and reduced responsiveness of mounting to exogenous EB and P in adulthood (defeminization). Prenatal treatment with 1 microgram DESDP produced similar but less pronounced effects. Prenatal treatment with 3.3 micrograms EB also caused a delay in puberty. However, responsiveness of lordosis to EB and P in adulthood was enhanced by treatment with either 1 or 3.3 micrograms EB prenatally. Further, neither mounting in the absence of hormones nor mounting in response to EB and P in adulthood were affected in any measurable way by any prenatal treatment with EB. These results show that estrogens can have masculinizing and defeminizing effects on sexually dimorphic reproductive traits in guinea pigs. The failure of EB to duplicate or parallel the effects of DESDP is not completely understood at this time, but it may indicate that less of the active substance reaches the target tissues following maternal and placental metabolism of EB than of DESDP.

The relationship between dominance and intermale mounting was analyzed in two troops of captive rhesus monkeys (Macaca mulatta). The data did not support the assumption that mounting among males functions as a dominance demonstration as described in the literature because mounting commonly (63% of 65 dyads) occurred in a bidirectional fashion, and mounting not only was performed by dominant males but also was shown with regularity (36% of 521 cases) by subordinate males. Intermale mounting was often (37% of 521 cases) associated with amicable interactions--commonly preceding them--but it was only rarely (2%) associated with dominance-subordination behaviors. It was concluded that intermale mounting may serve as a socially cohesive behavior in rhesus monkeys by promoting nonagonistic contact.