Oral contraceptive use in women is associated with defeminization of otoacoustic emission patterns.

The production of otoacoustic emissions (OAEs) by the cochlea is a sexually dimorphic trait. Although often hypothesized to be influenced by testosterone in utero, little attention has been devoted to the possibility that levels of circulating sex steroids in adulthood might modulate the sex difference in OAE production. The purpose of the current study was to investigate whether oral contraceptive (OC) use affects OAE production in women, revisiting a question originally posed by McFadden [(2000) Hearing Research 142:23-33]. Forty-five males and 50 females were tested. The women were retrospectively classified based on whether or not they were using OCs at present. Two types of OAEs were quantified: those produced spontaneously (spontaneous otoacoustic emissions or SOAEs) and those produced in response to click stimuli (click-evoked otoacoustic emissions or CEOAEs). Women currently using OCs showed a defeminized pattern of OAE production: they produced fewer SOAEs, SOAEs with significantly less power, and smaller CEOAE response amplitudes compared with naturally cycling women who were tested irrespective of phase of the menstrual cycle. It is proposed that the observed group difference may be mediated by the interaction of circulating estradiol with estrogen receptor alpha (ERα) or estrogen receptor beta (ERß) receptors in the cochlea.

Adverse physiological events under anaesthesia and sedation: a pilot audit of electronic patient records.

Review of perioperative activity including adverse events, throughput and compliance with 'best practice', can theoretically be used to optimise healthcare delivery. Computer-based analysis of electronic patient records could provide a practical means to manage quality improvement. This pilot study examined the effectiveness of such a system in practice. All intraoperative patient notes and physiological data were collected over 17 months in a rural hospital using data from an electronic record-keeping system. Algorithms were developed to automatically identify potential adverse events based on physiological measures. Each computer-identified event was reviewed by a panel of three anaesthetists and assessed for validity, severity and probable cause. Two areas were identified to pilot quality improvement activities-sedation for colonoscopies and inhalational anaesthesia with desflurane. Specific 'in-house' guidelines were created for these procedures and feedback on the patterns of adverse events were provided to anaesthetic staff A total of 138 separate adverse events were identified for all operative cases over 17 months, with an overall adverse event incidence of 3.3%. The adverse event incidence during colonoscopy and laryngospasm/hypoxia during desflurane anaesthesia was 6.3% and 1.3% respectively. This decreased to 2.8% (P <0.005) and 0.13% (P <0.0001) respectively for the nine months following feedback and the introduction of guidelines. Anaesthesia information systems can be an effective quality improvement tool and may enhance existing tools such as incident reporting systems.

Protothecosis in 17 Australian dogs and a review of the canine literature.

Systemic protothecosis was diagnosed in 17 Australian dogs between 1988 and 2005. There was a preponderance of young-adult (median 4 years), medium- to large-breed dogs. Females (12/17 cases) and Boxer dogs (7 cases, including 6 purebreds and one Boxer cross) were over-represented. Sixteen of 17 dogs died, with a median survival of four months. A disproportionate number of cases were from coastal Queensland. In most patients, first signs were referable to colitis (11/17 cases), which varied in severity, and was often present for many months before other symptoms developed. Subsequent to dissemination, signs were mostly ocular (12 cases) and/or neurologic (8 cases). Two dogs had signs due to bony lesions. Once dissemination was evident, death or euthanasia transpired quickly. Prototheca organisms had a tropism for the eye, central nervous system (CNS), bone, kidneys and myocardium, tissues with a good blood supply. Microscopic examination and culture of urine (5 cases), cerebrospinal fluid (CSF;1 case), rectal scrapings (4 cases), aspirates or biopsies of eyes (5 cases) and histology of colonic biopsies (6 cases) as well as skin and lymph nodes (2 cases) helped secure a diagnosis. Of the cases where culture was successful, P wickerhamii was isolated from two patients, while P zopfii was isolated from five. P zopfii infections had a more aggressive course. Treatment was not attempted in most cases. Combination therapy with amphotericin B and itraconazole proved effective in two cases, although in one of these treatment should have been for a longer duration. One surviving dog is currently still receiving itraconazole. Protothecosis should be considered in all dogs with refractory colitis, especially in female Boxers.

Genetic heterogeneity of day blindness in Alaskan Malamutes.

Day blindness is a progressive and specific degeneration of cone photoreceptors in the retina of young dogs. This disorder has been associated with a breed-specific non-synonymous substitution in exon 6 of the cyclic nucleotide gated channel beta3 (CNGB3) gene in German Shorthaired Pointer dogs and a genomic deletion removing the entire gene in Alaskan Malamute dogs from the USA. To further investigate this disorder, we characterized CNGB3 in a three-generation pedigree of Alaskan Malamute dogs from Australia segregating for day blindness. Fifteen of the dogs showed clinical signs of day blindness. Four of these were definitively diagnosed by standardized electroretinography. Polymerase chain reaction amplification of exon 6 of CNGB3 was attempted, and as expected, amplification was successful in the 18 unaffected or carrier dogs. However, a non-mutated exon 6 was also amplified and sequenced in six of the 15 affected dogs. On sequencing each exon and exon/intron boundary in two such affected individuals and two unaffected individuals, three exonic substitutions and 12 intronic changes were noted. These sequence variations in affected individuals were also present in one or both unaffected dogs and so appear to have no obvious effect on the protein's function. Hence, day blindness shows genetic heterogeneity within the Alaskan Malamute population of Australia, a result that is somewhat unexpected given the relatively small effective population size of this breed.

Primary glaucoma in Burmese cats.

OBJECTIVE: To document the clinical signs and management of primary glaucoma in Burmese cats. DESIGN: A retrospective study of six affected Burmese cats, from 1996 to 2001. Procedure Six Burmese cats diagnosed with primary glaucoma were managed over periods varying from 3 months to 4.5 years. Clinical details were obtained from practice records. Gonioscopic examination of the drainage or iridocorneal angle in eyes of these affected cats was made. RESULTS: Six desexed female Burmese cats (ages 7.0 to 10.5 years) presented with complaints of either unilateral (n = 4) or bilateral (n = 2) red eye, dilated pupil or enlarged eye. In one of the affected cats, one eye had been enucleated prior to the commencement of the study, thus a total of 11 eyes were examined. Clinically, all affected eyes (n = 8) had injected episcleral blood vessels and elevated intraocular pressure. Gonioscopy revealed the presence of nine narrow and two closed iridocorneal angles. Medical therapy included topical 2% dorzolamide (n = 8), 0.5% timolol maleate (n = 1), 0.005% latanoprost (n = 1) and 0.5-1.0% prednisolone acetate (n = 8). Surgery was performed in six eyes using either diode laser (n = 5) and/or cryothermy (n = 2) and one eye was eviscerated, with implantation of a prosthesis. With therapy, five affected eyes maintained vision and normal intraocular pressure, one eye remained blind with normal intraocular pressure, one eye remained blind with elevated intraocular pressure and one eye was eviscerated. CONCLUSIONS: The Burmese cat may be predisposed to primary narrow-angle glaucoma. Early diagnosis and continuous antiglaucoma therapy can help control intraocular pressure and maintain vision.

A sex difference on a novel spatial working memory task in humans.

Neurophysiological and behavioral evidence suggests that the prefrontal cortex (PFC) may be sexually differentiated in nonhuman primates. The present study examined whether there are sex differences in working memory in humans that might reflect sexual differentiation of human PFC. Male and female undergraduates were administered a novel multitrial spatial working memory task (SPWM) and a verbal working memory task. In three experiments, females committed significantly fewer working memory errors and took significantly less time to reach criterion than males on the SPWM task. The female advantage was not accounted for by differences in general intellectual ability, attention, perceptual speed, incidental memory, or speed of verbal access. In Study 3, a sex difference was also observed on a measure of verbal working memory. The findings suggest that some prefrontal functions may be sexually differentiated in humans.

A beneficial effect of estrogen on working memory in postmenopausal women taking hormone replacement therapy.

Recent neurophysiological data suggest that the prefrontal cortex (PFC) may be susceptible to modulation by estrogen. In humans, the PFC mediates a number of cognitive processes that contribute to memory function, particularly working memory. The present study examined whether memory tasks that recruit PFC-dependent information processing might exhibit estrogen sensitivity in women. Performance on several memory tasks, including measures of working memory, was evaluated in three groups of postmenopausal women: (1) women who were tested when taking estrogen only (n = 38, M(age) = 55.1 years), (2) women who were tested when taking estrogen and a progestin concurrently (n = 23, M(age) = 55.9 years), and (3) women who were not taking hormone replacement therapy (n = 35, M(age) = 56.0 years). Estrogen users exhibited significantly better performance on a verbal task and on a spatial task, each with a prominent working memory component, but did not differ from nonusers on control tasks involving simple passive recall. These findings are consistent with the hypothesis that estrogen is active within PFC and is capable of influencing functions dependent on this region. The results of this study raise the possibility that estrogen may play a role in maintaining certain frontal lobe functions in women.

Salivary testosterone concentrations in left-handers: an association with cerebral language lateralization?

The level of testosterone exposure in early brain development may influence the direction or degree of cerebral language lateralization. Possible links between individual differences in testosterone levels and patterns of speech representation were investigated in 180 healthy young adults (97 left handed, 83 right handed) using the Fused Dichotic Words Test (T. Halwes, 1991). Among left-handed participants, significantly higher testosterone concentrations were observed in individuals with a left-ear advantage on dichotic listening than in individuals with a right-ear advantage. Among right-handed participants, the pattern of group differences in testosterone tended to be reversed, resulting in a statistically significant interaction. Results extend prior findings by S. D. Moffat and E. Hampson (1996a) and raise the possibility that higher testosterone is associated with patterns of brain organization in which speech and praxic functions are lateralized to the same hemisphere.

Morphology of the planum temporale and corpus callosum in left handers with evidence of left and right hemisphere speech representation.

In the present study we investigated planum temporale asymmetry and corpus callosum morphology in a sample of young adult left-handed males, using MRI. Two subgroups of left-handed males were identified on the basis of their differing speech lateralization patterns, which were inferred from results of the Fused Dichotic Words Test. These individuals then underwent MRI in order to obtain area measurements of the left and right planum temporale and the midsagittal corpus callosum. Comparisons between these left-handed males and an archival sample of age-matched right-handed males were also performed. Results demonstrated a strong leftward asymmetry in the planum temporale among subjects with left-hemisphere speech representation, regardless of handedness, but no consistent planum temporale asymmetry among subjects with right hemisphere speech representation. The results suggest that reversed speech lateralization is not necessarily accompanied by a concomitant reversal of planum temporale asymmetry. Examination of callosal areas revealed that left-handed subjects with left hemisphere speech functions had a larger corpus callosum than either left-handed subjects with right hemisphere speech functions or right-handed subjects. Increased interhemispheric communication may be required when the neural systems underlying speech and handedness are represented in opposite hemispheres.

Testosterone is correlated with regional morphology of the human corpus callosum.

Theoretical speculation in humans (S.F. Witelson, Psychoneuroendocrinology 16 (1991) 131-153) and empirical findings in animals (R.H. Fitch, P.E. Cowell, L.M. Schrott, V.H. Denenberg, Int. J. Dev. Neurosci. 9 (1991) 35-38) suggest that testosterone (T) may play a significant role in the development of the corpus callosum (CC). However, there are currently no empirical studies directly relating T concentrations to callosal morphology in humans. The purpose of the present study was to investigate the relationship between free T concentrations as determined by radioimmunoassay, and the mid-sagittal area of the corpus callosum, as determined by magnetic resonance imaging (MRI). Subjects were 68 young adult (20-35 years), neurologically normal, right-handed males. All subjects underwent MRI and provided two samples of saliva for radioimmunoassay of T and cortisol. Anatomical regions of interest included total brain volume, left and right hemisphere volume and regional areas of the CC. CC regions were defined using two different measurement techniques, each dividing the CC into six sub-sections. Anatomical measurements were performed blind with respect to the hormone levels of subjects. A significant positive correlation between T concentration and cross-sectional area of the posterior body of the CC was found. This finding was consistent across the two measurement techniques and was not attributable to individual differences in total brain volume. All correlations between cortisol and CC sub-regions were non-significant. The results of this study are consistent with the notion that T, at an earlier stage in development, may play a significant role in modulating cortical/callosal architecture in humans.

Turning bias in humans is influenced by phase of the menstrual cycle.

Previous studies have provided evidence that humans demonstrate subtle, but measurable, turning biases when tested in the absence of environmental constraints. Preferences for leftward or rightward rotation have been repeatedly demonstrated in rodents and appear to be modulated to a significant degree by ovarian hormones, particularly estrogen. In the present study, we examined the turning biases of adult women at the midluteal and menstrual phases of the menstrual cycle, associated with high and low levels of estradiol and progesterone, respectively. Saliva samples were collected during each test session, and salivary concentrations of estradiol and progesterone were measured using radioimmunoassays. Overall, a rightward-turning bias was evident; however, a minority of the women displayed consistent leftward biases. Among right-turning subjects, turning biases were significantly weaker at the midluteal phase than at the menstrual phase. These results suggest that the mechanisms underlying human turning biases are subject to modulation by ovarian hormones.

Evolution and the hormonal control of sexually-dimorphic spatial abilities in humans.

A number of hypotheses have been proposed for the evolution of sex differences in spatial ability. Two of these hypotheses assume a sex-based division of labor in foraging during human evolutionary history, three propose sexual selection for spatial ability, and two suggest that human life history has imposed sex-specific selection on spatial abilities. We derive predictions from each of these models and test the predictions against recent data on the effects of hormones on spatial ability across the lifespan. Sexual selection for increased range size in males might be the evolutionary origin of the enhancing effects of testosterone on spatial ability, while the benefits of reduced mobility in women at different stages of reproduction could be the origin of the inhibitory effects of oestrogen on spatial ability.

A sex difference in turning bias in humans.

A large body of literature has documented the existence of individual preferences in turning direction among rodents which appear to be dependent on striatal dopaminergic mechanisms. Recent work has indicated that humans also demonstrate individual turning preferences, and that these preferences may also be related to the nigrostriatal dopamine system. We describe here a new method for measuring turning preferences in humans and report a sex difference in the magnitude of the directional preference. While both males and females tended to turn towards the right, this tendency was significantly stronger among females. Analyses of test-retest reliability across two sessions (1-2 weeks apart) indicated that, in general, the rotation task elicited consistent turning biases. However, the turning biases of males and of females using oral contraceptives were significantly more consistent than those of regularly cycling females. These results are compatible with the animal literature and provide indirect evidence that ovarian hormones may modulate the mechanism(s) underlying this motor asymmetry.

A curvilinear relationship between testosterone and spatial cognition in humans: possible influence of hand preference.

The nature of the relationship, if any, between performance on visuo-spatial tests in humans and circulating testosterone (T) concentrations remains controversial. We investigated possible relationships between salivary T and cortisol (C) concentrations and performance on visuo-spatial and verbal cognitive tests in a sample of healthy young adults. Among right-handers, salivary T was found to be negatively correlated with spatial performance in males, but was positively correlated with a measure of spatial visualization in females. This pattern was not evident in left-handers. Across the entire observed range of T, the relationship between spatial cognition and T was best described by an inverted quadratic function in right-handers, but not in left-handers. A significant difference in spatial accuracy was seen among right-handers tested in early vs. late morning testing sessions, in accordance with the expected diurnal change in circulating T. No significant relationships between salivary C and visuo-spatial performance were found. These results are consistent with prior literature suggesting a curvilinear relationship between spatial performance and circulating T concentrations, with intermediate levels of T being associated with better spatial functioning, but raise the possibility that hand preference may be one factor that moderates the observed relationship.

Salivary testosterone levels in left- and right-handed adults.

It has been proposed that prenatal testosterone (T) may contribute to the development of hand preference and cerebral functional asymmetry in humans. To investigate any persisting association between T and asymmetry in adulthood, left-handed (LH) and right-handed (RH) men and women were administered a hand preference questionnaire and the Fused Dichotic Words Test. Testosterone was measured in samples of saliva. Results showed that LH subjects of both sexes had lower salivary T concentrations than their RH counterparts. Among LH males, subjects with a right-ear advantage in dichotic listening tended to have lower T concentrations than subjects with a left-ear advantage. These results are consistent with the notion that T may be involved in the development of hand preference and cerebral functional asymmetry.

Spatial cognition in humans: possible modulation by androgens and estrogens.

Many studies in nonhuman species have shown that gonadal steroid hormones can influence the regional structure and physiology of the central nervous system, and can bring about both short- and long-term effects on behavior. The extent to which human behavior and thought processes are subtly influenced by the hormonal milieu is unclear. There is preliminary evidence from a number of clinical endocrine syndromes, and from studies of normal human subjects, that sex steroids may modulate the expression of certain specific cognitive abilities. This paper will briefly review some recent evidence suggesting that visual-spatial abilities are among the cognitive functions that may be affected.

Heterogeneous morphology and tracer coupling patterns of retinal oligodendrocytes.

The present study characterizes the morphology and tracer coupling patterns of oligodendrocytes in the myelinated band of the rabbit retina, as revealed by intracellular injection of biocytin or Lucifer yellow in an isolated superfused preparation. Based on the observed heterogeneity in morphology, we have grouped the presumptive oligodendrocytes into three categories termed 'parallel', 'stratified' and 'radial'. Most parallel oligodendrocytes were tracer coupled to nearby oligodendrocytes and astrocytes, whereas the stratified and radial oligodendrocytes rarely showed coupling. We conclude that the different categories of oligodendrocytes may be stages in a developmental series, with radial oligodendrocytes being premyelinating cells, parallel oligodendrocytes being mature myelinating cells and the stratified cells representing a transition between these categories.

Gonadal hormone levels and spatial learning performance in the Morris water maze in male and female meadow voles, Microtus pennsylvanicus.

The present study examined the relationships between spatial learning and circulating levels of plasma estradiol and testosterone in adult male and female meadow vole, Microtus pennsylvanicus. Meadow voles are induced ovulators and most females that are housed with females or in isolation are in constant diestrus, whereas most females that are housed with males are in constant behavioral estrus. In this study sexually mature, adult male and female meadow voles housed with either females (constant diestrus) or males (constant behavioral estrus) were required to learn the spatial position of a hidden, submerged platform in the Morris water maze. Individual voles were tested using two blocks of four trials twice a day for 3 days for a total of six blocks. Task retention was examined with a probe trial 1 day after the last acquisition trial. Females were divided into two groups based on the median level of plasma estradiol [High Estradiol (15.79 +/- 1.20 pg/ml) and Low Estradiol (6.22 +/- 2.79 pg/ml) Females]. Males were similarly divided on the basis of median plasma testosterone levels [High (2.53 +/- 0.96 ng/ml) and Low Testosterone (0.45 +/- 0.08 ng/ml) Males]. High Estradiol females exhibited significantly longer latencies to reach the hidden platform, indicating poorer acquisition, than did either males (P = 0.025) or Low Estradiol females (for Blocks, 2, 3, 4, and 6, P = 0.037). Male superiority in spatial learning performance was evident only when High Estradiol females were compared to males. There were no significant performance differences between High and Low Testosterone males. There were also no group differences in retention, with all voles displaying significant retention of the spatial task. There was, however, a significant correlation between plasma estradiol levels in females and retention, with higher estradiol levels being associated with poorer retention. These results suggest that levels of estradiol in adult female meadow voles are significantly related to spatial learning, with low levels of estradiol being associated with better spatial learning. There was no evidence that levels of testosterone were related to spatial performance in adult male meadow voles. The results suggest that estradiol may have activational effects on spatial learning in the adult meadow vole and that sex differences in spatial learning are evident only when High Estradiol females are compared to adult males.