Infertility as a lonely struggle? Coping stories of previously infertile women.

In this narrative study, we explored the meaning infertile women attribute to social support in coping with their infertility-related challenges. Written accounts and episodic interviews with 26 previously infertile Finnish women were used as data. Two different coping story types emerged: coping alone and coping with support. In the coping alone type women neither sought nor received support. Their coping appeared as a lonely struggle. In the coping with stories, women turned to their spouses, peers, or professionals, but still emphasized that they would have needed more support. Based on our findings, we underline the need for individually tailored support.

Urinary 6-hydroxymelatonin sulfate excretion in intellectually disabled subjects with sleep disorders and multiple medications: validation of measurements in urine extracted from diapers.

The aim of this study was to examine the applicability of urinary 6-hydroxymelatonin sulfate (MT6s) measurements in the evaluation of melatonin secretion in intellectually disabled patients with sleep disorders. All 17 patients received drugs with potential interactions with melatonin metabolism. Serum melatonin 24-h profiles were determined at hourly intervals. The area under the curve (AUC) value, peak amplitude, half-rise time, and half-decline time were calculated individually. Urinary MT6s excretion was determined from samples collected from disposable diapers during three consecutive days at varying intervals. The average excretion rate for each hour of the day was calculated. The excretion profiles were characterized by total amount of MT6s excretion/24 h/kg body mass, amount of excreted MT6s during 6 h of maximum excretion (MAX 6h), and start time of the maximum excretion (start MAX 6h). There were significant positive correlations between serum melatonin AUC value and total excretion of MT6s/body mass, between serum melatonin amplitude and urinary MAX 6h, and between melatonin half-rise time and start MAX 6h; one patient on phenobarbital medication was out of line. The serum melatonin profiles of the patients were classified by comparing them with those of matched healthy volunteers (low-, normal-, or high secretors, normal or delayed rhythm). Similarly, the parameters of MT6s profiles were compared with those obtained from healthy controls, and the patients were reclassified as normal or aberrant. The classifications based on serum melatonin and urinary MT6s measurements were mostly concordant. The daily pattern of urinary MT6s excretion reliably reflected the phase of the serum melatonin rhythm irrespective of the medications, but in some cases, the total amount of excreted MT6s was lower than expected based on serum melatonin measurements.

Early development of children at familial risk for dyslexia--follow-up from birth to school age.

We review the main findings of the Jyväskylä Longitudinal study of Dyslexia (JLD) which follows the development of children at familial risk for dyslexia (N = 107) and their controls (N = 93). We will illustrate the development of these two groups of children at ages from birth to school entry in the skill domains that have been connected to reading and reading disability in the prior literature. At school entry, the highest score on the decoding task among the poorer half (median) of the at risk children--i.e. of those presumably being most likely genetically affected--is 1 SD below the mean of the control group. Thus, the familial risk for dyslexia shows expected consequences. Among the earliest measures in which group differences as well as significant predictive associations with the first steps in reading have emerged, are indices of speech processing in infancy. Likewise, various measures of early language including pronunciation accuracy, phonological, and morphological skills (but not performance IQ) show both group differences and predictive correlations, the majority of which become stronger as the reliability of the measures increases by age. Predictive relationships tend to be strong in general but higher in the at risk group because of its larger variance in both the predictor variables and in the dependent measures, such as early acquisition of reading. The results are thus promising in increasing our understanding needed for early identification and prevention of dyslexia.

Language development and symbolic play in children with and without familial risk for dyslexia.

The purposes of this study were to investigate (a) whether children in families with a positive history of dyslexia were more likely to show delays in language development than children without family risk and (b) whether a delayed onset of expressive language (late talking) predicted later language development. We analyzed the language development of 200 children longitudinally at 14, 24, 30, and 42 months and assessed their symbolic play at 14 months. Half of the children (N = 106) were from families with a history of dyslexia (the Dyslexia Risk [DR] group), and other children served as age-matched controls. Parental reports and structured tests were used to assess children's receptive and expressive language and symbolic play. No differences emerged between the two groups in receptive language, symbolic play, or on the Bayley MDI. The groups, however, diverged in expressive language measures. The maximum sentence length at 2 years and object naming and inflectional morphology skills at 3.5 years were higher for the control group than for the DR group. Reynell receptive score at 2.5 years provided the greatest unique contribution to the prediction of the children's receptive and expressive language. Children's risk status did not contribute to receptive language, but provided a significant contribution to their expressive language at 3.5 years, even after the variance associated with parental education and children's previous language skills was controlled. Late talkers in the DR group differed from the other members of the DR group in both receptive and expressive language at 3.5 years, although in the control group children with a late-talking history performed at age-level expectations. The findings suggest that children with a familial risk for dyslexia and with a history of late talking are at higher risk for delays in language acquisition than children without the familial risk for dyslexia.

Seasonal variation in endogenous serum melatonin profiles in goats: a difference between spring and fall?

The pineal hormone melatonin serves as a signal of day length in the regulation of annual rhythms of physiological functions and behavior. The duration of high melatonin levels in body fluids is proportional to the duration of the dark period of the day. Due to the direct suppression of melatonin by light, the overt melatonin rhythm may differ from the endogenous rhythm driven by the hypothalamic circadian clock. The aim of this study was to find out possible differences between the overt and endogenous melatonin rhythms in goats during the course of a year. Seven Finnish landrace goats (nonlactating females) were kept under artificial lighting that approximately simulated the annual changes of day length at 60 degrees N. Blood samples for melatonin measurements by radioimmunoassay were collected at 2-h intervals during six seasons: winter (light:dark 6:18 h), early spring (10:14), late spring (14:10), summer (18:6), early fall (14:10), and late fall (10:14). Melatonin profiles were determined for 2 consecutive days, first in light-dark (LD) conditions and then in continuous darkness (DD). In LD conditions, the profiles matched the dark period with one exception: In winter, the mean peak duration was significantly shorter than the scotoperiod. In DD conditions, two types of endogenous melatonin patterns were found: a "winter pattern" (peak duration 13-15 h) in winter, early spring, early fall, and late fall, and a "summer pattern" (duration about 11 h) in late spring and summer. Thus, in equal habitual LD conditions in late spring and early fall (LD 14:10), the endogenous melatonin rhythms were not quite similar: The pattern in late spring resembled that in summer, and the pattern in early fall that in winter. These results suggest that, in addition to the light-adjusted overt melatonin rhythm, the endogenous rhythm of melatonin secretion varies during the course of a year.

Neurological impairments and sleep-wake behaviour among the mentally retarded.

The objective of the present study was to evaluate the relationship between the sleep-wake behaviour and neurological impairments among mentally retarded people. The sleep-wake behaviour of 293 mentally retarded subjects living in a rehabilitation center was studied by a standardized observation protocol carried out by trained staff members. The protocol consisted of brief check-ups of the subjects' sleep-wake status at 20-min intervals for five randomly chosen 24-h periods during 4 months. From the raw data five sleep-wake behaviour variables were formed. The data concerning the subject characteristics (age, body mass index (BMI), gender, degree of mental retardation, presence of locomotor disability, that of epilepsy, blindness or deafness and the usage of psychotropic medications) were collected from the medical records. Two main findings emerged: (1) severe locomotor disability, blindness and active epilepsy were found to be independent predictors of increased daytime sleep and increased number of wake-sleep transitions and (2) the subjects with a combination of two or all three of these impairments had a significantly more fragmented and abnormally distributed sleep than those with none or milder forms of these impairments. Age, BMI, degree of mental retardation and the studied medications played a minor role in the sleep disturbances of the study population. Finally, deafness was not found to be associated with any of the measured sleep-wake variables.

Developmental pathways of children with and without familial risk for dyslexia during the first years of life.

Comparisons of the developmental pathways of the first 5 years of life for children with (N = 107) and without (N = 93) familial risk for dyslexia observed in the Jyväskylä Longitudinal study of Dyslexia are reviewed. The earliest differences between groups were found at the ages of a few days and at 6 months in brain event-related potential responses to speech sounds and in head-turn responses (at 6 months), conditioned to reflect categorical perception of speech stimuli. The development of vocalization and motor behavior, based on parental report of the time of reaching significant milestones, or the growth of vocabulary (using the MacArthur Communicative Development Inventories) failed to reveal differences before age 2. Similarly, no group differences were found in cognitive and language development assessed by the Bayley Scales of Infant Development and the Reynell Developmental Language Scales before age 2.5. The earliest language measure that showed lower scores among the at-risk group was maximum sentence length at age 2. Early gross motor development had higher correlation to later language skills among the at-risk group rather than the control children. The most consistent predictor of differential development between groups was the onset of talking. Children who were identified as late talkers at age 2 were still delayed at the age 3.5 in most features of language-related skills-but only if they belonged to the group at familial risk for dyslexia. Several phonological and naming measures known to correlate with reading from preschool age differentiated the groups consistently from age 3.5. Our findings imply that a marked proportion of children at familial risk for dyslexia follow atypical neurodevelopmental paths. The signs listed previously comprise a pool of candidates for early predictors and precursors of dyslexia, which await validation.

No evidence for extraocular light induced phase shifting of human melatonin, cortisol and thyrotropin rhythms.

The view that light affects the mammalian circadian clock only through the eyes was recently challenged by a study in which the phases of human circadian rhythms were shifted by extraocular light exposure. This finding has not been confirmed, however. We studied the effects of light exposure (3 h, broad spectrum fluorescent white light, 13000 lux) on abdomen and chest on the circadian rhythms of serum melatonin, cortisol and thyrotropin in six subjects. The protocol consisted of two 3-day sessions in a dimly lit (< 10 lux) experimental unit. In both sessions hourly serum samples were collected for hormone analysis on days 1 and 3. The skin light exposure was delivered on day 2 from 22.00 to 01.00h in one of the two sessions in a randomized order. In both sessions all three rhythms tended to delay, presumably due to the endogenous circadian cycle length being slightly longer than 24 h. However, the phase shifts did not differ significantly between the sessions. Thus, the present study does not support the existence of extraocular photic regulation of the circadian rhythms in humans.

Melatonin release from rat pineals in vitro is stimulated by both the alpha(2)-adrenoceptor agonist medetomidine and the antagonist atipamezole.

This study was done to clarify the role of alpha(2)-adrenoceptors in the regulation of pineal melatonin synthesis. Rat pineal glands were incubated in oxygenated Krebs-Ringer solution in perifusion chambers, and perifused for 30 min with alpha(2)-adrenoceptor ligands. The melatonin concentrations were measured from the perifusate by radioimmunoassay. Both medetomidine and atipamezole (>/=10(-5) M) increased melatonin release. Yohimbine blocked the increase caused by medetomidine but not by atipamezole. The effects of medetomidine and atipamezole were also additive: the maximum response to atipamezole could be significantly increased by medetomidine. These results suggest that the two drugs stimulate the melatonin synthesis through different mechanisms: medetomidine through alpha(2)-adrenoceptors and atipamezole possibly through nonadrenergic mechanisms. The results differ from previous in vivo experiments suggesting that alpha(2)-adrenoceptor ligands affect melatonin synthesis both centrally and locally in the pineal gland. The local effects are most likely masked under the central regulatory systems in vivo.

The development and predictive relations of play and language across the second year.

The play and language development of 171 toddlers was examined at 14 and 18 months by observing their activities on the Symbolic Play Test and by assessing their language skills using the MacArthur Communicative Development Inventories (MCDI) and the Reynell Developmental Language Scales. Additionally, data from the Bayley Scales of Infant Development and the MCDI were obtained at 24 months, in order to investigate how play and language measures taken at 14 and 18 months predict children's development at the age of 2 years. The results showed that the vocabulary production and symbolic play of the 14-month-old toddlers made a unique contribution to their language and cognitive skills at the age of 2 years, while at 18 months only language variables made a similar contribution. Other-directed pretense discriminated between the children's subsequent language and cognitive skills best, whereas nonsymbolic play had no independent predictive contribution. Significant gender differences were found in the use of nonsymbolic and symbolic play acts already at 14 months. Gender did not, however, contribute to the prediction of the children's subsequent skills, whereas maternal education significantly added to the prediction of the 2-year-olds' maximum sentence length and that of their cognitive development.

Suppression of melatonin by 2000-lux light in humans with closed eyelids.

BACKGROUND: In order to clarify the role of light in regulating body functions in sleeping humans, we studied whether the light-sensitive pineal hormone melatonin can be suppressed by facial light exposure in subjects with closed eyelids. METHODS: Eight healthy volunteers participated in 3 nightly sessions: a dim-light control session (< 10 lux) and two light-exposure sessions (2000 lux, 60 min between 2400 and 0200 h). One light exposure occurred with eyes open and the other with eyes closed. Saliva samples were collected at least every hour from 1900 to 0300 h. Melatonin concentrations were measured by radioimmunoassay. RESULTS: Salivary melatonin concentrations decreased only in 2 of the 8 volunteers during light-exposure sessions with eyes closed. On average, light exposure did not decrease the salivary melatonin concentration. CONCLUSIONS: Because indoor illuminance is usually much lower than 2000 lux, light is probably ineffective in regulating the neuroendocrine hypothalamic functions in people during their sleep. Nevertheless, the possibility remains that higher illuminances, often used for therapeutic purposes, can inhibit the secretion of melatonin even in sleeping patients.

Evidence against alpha2-adrenoceptor involvement in the regulation of rat melatonin synthesis by ambient lighting.

This study was carried out to clarify the role of alpha2-adrenoceptors in the regulation of pineal melatonin synthesis. Medetomidine, a selective alpha2-adrenoceptor agonist, was previously found to be a potent suppressor of nocturnal melatonin levels in rats. Medetomidine and alpha2-adrenoceptor antagonists atipamezole and yohimbine were injected into rats in different conditions, and their pineal melatonin contents were measured by radioimmunoassay. Experiment 1: Blocking the alpha2-adrenoceptors and possible non-adrenergic binding sites with atipamezole did not counteract the light-induced suppression of nocturnal melatonin. These receptors are, thus, not essential for the suppression of melatonin by light. Experiment 2: Blocking the alpha2-adrenoceptors with atipamezole or yohimbine did not sensitize the pineal melatonin synthesis to daytime darkness in the light/dark-entrained rats. The binding sites are not involved in keeping the daytime melatonin levels low, even in darkness. Experiment 3: The rats were sensitized to daytime darkness by keeping them for seven days in constant light. The dark-elicited melatonin rise was suppressed by a lower dose of medetomidine than the normal nocturnal rise in light/dark-entrained rats, while atipamezole had no effect. The results showed that alpha2-adrenoceptor insufficiency is not involved in the constant light-induced pineal supersensitivity. In summary, the experiments indicated that the physiological regulation of melatonin synthesis by ambient lighting in rats does not depend on alpha2-adrenergic mechanisms.

Melatonin ineffective in neuronal ceroid lipofuscinosis patients with fragmented or normal motor activity rhythms recorded by wrist actigraphy.

Melatonin was tested as a sleeping pill in five patients with neuronal ceroid lipofuscinoses. The single-blind, placebo-controlled study consisted of motor activity recordings, sleep logs, and administration of placebo or melatonin (2.5 or 5 mg). Daily motor activity rhythms were measured by wrist actigraphy during four 7-day periods (baseline, placebo, melatonin 2.5 mg, and melatonin 5 mg). The placebo or melatonin was administered in the evenings for 3 weeks, and the recordings were made during the last week of the 3-week treatment. Sleep logs were kept by the caregivers during the recordings. Based on period analyses, the activity recordings were evaluated to display a normal (24-h) or fragmented rhythm. Three patients had normal motor activity patterns during the baseline recordings, and administration of placebo or melatonin did not affect their rest/activity rhythms. Two patients had abnormally fragmented activity rhythms during the baseline periods, and administration of placebo or melatonin did not induce synchronization. According to the actigraphic data, there were no changes in activity rhythms resulting from administration of melatonin. However, based on the observations, three families reported that melatonin slightly improved the sleep quality of the patients. These controversial findings show the difficulties involved in specifying the role of melatonin in modulating sleep. Thus, we conclude that more evidence is required before the significance of melatonin as a sleeping pill is defined.

Bright light suppresses melatonin in blind patients with neuronal ceroid-lipofuscinoses.

We studied whether light information can reach the pineal glands of clinically blind patients with neuronal ceroid-lipofuscinoses. The suppression of melatonin by light was used as an indicator. Seven patients and seven control subjects were exposed to 3,000-lux light for 60 minutes at the rising phase of the melatonin synthesis. Most patients were not cooperative, and their eyelids were opened by a researcher every 2 minutes for 2 seconds. The control subjects opened and closed their eyes similarly by themselves. Light suppressed melatonin in three of seven control subjects and in all patients. The average postlight levels were 80% (control subjects) and 51% (patients) of the corresponding levels during the dim-light session. Despite degenerated retinas of the blind patients, light can penetrate their visual system to the hypothalamic and pineal levels and regulate neuroendocrine function.

Pineal melatonin in rats: suppression by the selective alpha2-adrenoceptor agonist medetomidine.

This study was done to clarify the role of alpha2-adrenoceptors in the regulation of pineal melatonin synthesis. A selective alpha2-adrenoceptor agonist, medetomidine, and antagonist, atipamezole, were injected subcutaneously into rats and their pineal melatonin contents were measured by radioimmunoassay. Medetomidine (120 microg/kg) suppressed melatonin at night to a similar extent during the rising and descending phase of melatonin synthesis, but it did not affect the daytime level. A dose of 12 microg/kg was ineffective; doses of 30-180 microg/kg suppressed nocturnal melatonin levels close to the daytime levels. Significant suppression was reached within 15 min and the effect started to fade 3 h after the injection (120 microg/kg). At midday, medetomidine did not inhibit isoproterenol-stimulated synthesis of melatonin. Atipamezole (0.4 or 1.2 mg/kg) had no effect alone, but it counteracted the medetomidine-induced suppression. The effects of alpha2-adrenoceptor ligands on melatonin synthesis depend on the time of day and/or on the activity of the pineal sympathetic nerves.

Categorization of voice disorders with six perceptual dimensions.

To obtain a perceptual reference for acoustic feature selection, 94 male and 124 female voices were categorized using the ratings of 6 clinicians on visual analog scales for pathology, roughness, breathiness, strain, asthenia, and pitch. Partial correlations showed that breathiness and roughness were the main determinants of pathology. The six-dimensional ratings (the six median scores for each voice) were categorized with the aid of the Sammon map and the self-organizing map. The five categories created differed with respect to the breathiness/roughness ratio and the degree of pathology.

Alpha2-adrenoceptor agonist medetomidine affects the melatonin rhythm in rats.

We investigated whether alpha2-adrenergic mechanisms participate in the regulation of the daily melatonin rhythm. Female Wistar rats, living under 12:12 h light-dark conditions, received a subcutaneous injection of saline or medetomidine (alpha2-adrenoceptor agonist; 100 microg/kg) 1 h after lights off. Thereafter they were kept in continuous darkness. Pineal glands were collected for melatonin measurements at 2-h intervals during the first and second subjective nights. During both nights, a significant elevation of melatonin levels in medetomidine-injected rats was found 2 h later than in control rats. We interpret the first-night delay to be a sign of medetomidine's suppressive effect on melatonin synthesis, and the second-night delay a medetomidine-induced resetting of the circadian clock controlling the melatonin onset.

Ontogeny of pineal melatonin rhythm in rats under 12:12-hr and 14:14-hr light:dark conditions.

The aim of the study was to determine whether a discrepancy between the genetically determined endogenous circadian period and an abnormally long Zeitgeber period disturbs the development of melatonin synthesis. Breeding pairs of rats were kept under 12:12- or 14:14-hr light:dark (LD) conditions. Pineal melatonin contents in the offspring were measured by radioimmunoassay. At 2 weeks of age high melatonin contents were found from lights-off to lights-on in both conditions suggesting dominance of the photic regulation. At 3 weeks of age the signs of the circadian regulation in the melatonin profiles were evident: a lag period after the light offset in control conditions and a significant decline before the light onset in both conditions. However, in 14:14-hr LD conditions the melatonin content did not decrease to daytime levels until the lights were on. This could suggest incomplete maturation of the circadian system. The phase relationships between the melatonin peak and LD cycle were different in the two conditions. A statistically significant LD difference was first found at the age of 8-10 days in male pups and at 14 days in female pups under both lighting. The results suggest that the abnormally long LD cycle did not cause any major disorders in the development of photic or circadian regulation of the melatonin synthesis.

Exogenous melatonin fails to counteract the light-induced phase delay of human melatonin rhythm.

Salivary melatonin levels were measured in 6 healthy volunteers in order to determine whether the phase shift caused by a single 60-min light pulse of 2000 lux might be inhibited by maintaining high melatonin concentration. In the control sessions, the samples were collected at 60-min intervals under lighting of < 10 lux from 18.00 to 11.00 h. In the light-exposure sessions, placebo or 0.5 mg melatonin was administered orally 60 min prior to the light pulse, timed at the rising phase of the melatonin synthesis. The after-light sessions, one day after the light exposure, were like the control sessions. The average delays of the melatonin half-rise and half-decline times were equal (about 0.7 h) in the placebo and melatonin replacement experiments. The maintenance of high melatonin levels during the light exposure did not counteract the influence of bright light on the melatonin rhythm. Thus, in the adjustment of the melatonin rhythm, light is a stronger regulator than melatonin itself.

Daytime dark exposure increases pineal melatonin in rat pups.

Photic regulation of the pineal melatonin synthesis was studied in 3- to 21-day-old rat pups by exposing the animals to light at night (30-40 min) or to darkness during the day (30-240 min). The pineal melatonin contents were measured by radioimmunoassay. A significant day/night difference in the melatonin content and the nocturnal light-induced decrease were not found until second postnatal week. A novel finding was that at the age of 13-17 days a daytime dark exposure elevated the pineal melatonin content; it was twofold as compared with the normal daytime level and about half of the nocturnal peak level. In 21-day-old rats the response had disappeared, while the nocturnal suppression by light persisted. The dark-induced increase of the melatonin synthesis was independent of the opening of the eyelids which occurs in pups at the age of two weeks, but it was greater in maternally isolated than non-isolated pups. The results suggest that one component of the circadian regulatory system matures at the end of the third postnatal week. This mechanism inhibits the elevation of the melatonin synthesis by darkness during the daytime.