Eating disorders, weight perception, and dieting in adolescence

Background: Eating disorders are serious psychiatric disorders, which usually have their onset in adolescence. Body dissatisfaction and dieting, both common among adolescents, are recognised risk factors for eating disorders. The aim of the present study was to assess the prevalence of eating disorders in the general adolescent population, assess the risk of developing eating disorders in subgroups of dieters, and analyse longitudinal concomitants of incorrect weight perception. Method: A prospective follow-up study on 595 adolescents, aged 15 at baseline, was conducted in western Finland. The study comprised questionnaires directed at the whole study population and subsequent personal interviews with adolescents found to be screen-positive for eating disorders, at both baseline and three-year follow-up. Results: The lifetime prevalence rates for 18 year old females were 2.6 % for anorexia nervosa, 0.4 for bulimia nervosa, and 9.0 % for eating disorder not otherwise specified (EDNOS). No prevalent case of DSM-IV eating disorders was found among the male participants. Eating disorders, as well as depressive symptoms, social anxiety, and low self-esteem, was more prevalent among females who perceived themselves as being overweight, despite being normal or underweight, when compared to females with a correct weight perception. An incorrect weight perception was associated in males with social anxiety. Female adolescents dieting due to psychological distress, rather than vanity or overweight, had a fifteen-fold risk of developing an eating disorder. Conclusions: Eating disorders are common among female adolescents, and adolescents choosing to diet due to psychological distress show a markedly increased risk of developing an eating disorder. Promotion of general well-being as well as the prevention of body dissatisfaction and misdirected dieting, accompanied by early detection and proper treatment of eating disorders, is needed to reduce the incidence of and facilitate recovery in adolescents suffering from eating disorders.

Evaluation of common mental disorders in women with polycystic ovary syndrome and its relationship with body mass index

PURPOSE: To evaluate the prevalence of common mental disorders in women diagnosed with polycystic ovary syndrome as compared with paired controls without this syndrome. METHODS: Cross-sectional study with a Control Group examining women between the ages of 18 and 30 who did not use antidepressants and who sought the Gynecology Service of the researched sites. For every woman diagnosed with the polycystic ovary syndrome, another with the same age, educational status and presence or absence of sexual partners was sought without this diagnosis. In total, 166 patients agreed to participate, consisting of 95 diagnosed with polycystic ovary syndrome and 71 in the Control Group. The diagnosis of polycystic ovary syndrome was made by the presence of two from three criteria: oligomenorrhea or amenorrhea, clinical or biochemical hyperandrogenism and polycystic ovaries on transvaginal ultrasound, following exclusion of patients with Cushing's syndrome, congenital adrenal hyperplasia, and androgen-secreting tumors. Weight and height were measured to calculate the body mass index. The Self-Reporting Questionnaire, which evaluated 20 items, was used as an indicator of common mental disorders. A χ² analysis stratified by the category of body mass index was used to compare the prevalence of common mental disorders, between the groups of women with and without the polycystic ovary syndrome. RESULTS: There were no significant differences in age, education, presence of sexual partners, ethnicity, socioeconomic status, use of psychiatric medication, and search for consultation in mental health between the studied groups. The prevalence of obese women with indications of common mental disorders was significantly higher in women with polycystic ovary syndrome than in the Control Group. In the group with healthy body mass index, the incidence of common mental disorders was statistically significant different between women with polycystic ovary syndrome and normal controls (p=0.008). CONCLUSIONS: Women with diagnosis of this disease have an almost three-fold increased likelihood of common mental disorders as compared with those without polycystic ovary syndrome. Although obesity is often observed in polycystic ovary syndrome, even women with a healthy body mass index have an increased risk of psychiatric comorbidity.

Skill Development in Music Reading. The Eye-Movement Approach

This dissertation examined skill development in music reading by focusing on the visual processing of music notation in different music-reading tasks. Each of the three experiments of this dissertation addressed one of the three types of music reading: (i) sight-reading, i.e. reading and performing completely unknown music, (ii) rehearsed reading, during which the performer is already familiar with the music being played, and (iii) silent reading with no performance requirements. The use of the eye-tracking methodology allowed the recording of the readers’ eye movements from the time of music reading with extreme precision. Due to the lack of coherence in the smallish amount of prior studies on eye movements in music reading, the dissertation also had a heavy methodological emphasis. The present dissertation thus aimed to promote two major issues: (1) it investigated the eye-movement indicators of skill and skill development in sight-reading, rehearsed reading and silent reading, and (2) developed and tested suitable methods that can be used by future studies on the topic. Experiment I focused on the eye-movement behaviour of adults during their first steps of learning to read music notation. The longitudinal experiment spanned a nine-month long music-training period, during which 49 participants (university students taking part in a compulsory music course) sight-read and performed a series of simple melodies in three measurement sessions. Participants with no musical background were entitled as “novices”, whereas “amateurs” had had musical training prior to the experiment. The main issue of interest was the changes in the novices’ eye movements and performances across the measurements while the amateurs offered a point of reference for the assessment of the novices’ development. The experiment showed that the novices tended to sight-read in a more stepwise fashion than the amateurs, the latter group manifesting more back-and-forth eye movements. The novices’ skill development was reflected by the faster identification of note symbols involved in larger melodic intervals. Across the measurements, the novices also began to show sensitivity to the melodies’ metrical structure, which the amateurs demonstrated from the very beginning. The stimulus melodies consisted of quarter notes, making the effects of meter and larger melodic intervals distinguishable from effects caused by, say, different rhythmic patterns. Experiment II explored the eye movements of 40 experienced musicians (music education students and music performance students) during temporally controlled rehearsed reading. This cross-sectional experiment focused on the eye-movement effects of one-bar-long melodic alterations placed within a familiar melody. The synchronizing of the performance and eye-movement recordings enabled the investigation of the eye-hand span, i.e., the temporal gap between a performed note and the point of gaze. The eye-hand span was typically found to remain around one second. Music performance students demonstrated increased professing efficiency by their shorter average fixation durations as well as in the two examined eye-hand span measures: these participants used larger eye-hand spans more frequently and inspected more of the musical score during the performance of one metrical beat than students of music education. Although all participants produced performances almost indistinguishable in terms of their auditory characteristics, the altered bars indeed affected the reading of the score: the general effects of expertise in terms of the two eye- hand span measures, demonstrated by the music performance students, disappeared in the face of the melodic alterations. Experiment III was a longitudinal experiment designed to examine the differences between adult novice and amateur musicians’ silent reading of music notation, as well as the changes the 49 participants manifested during a nine-month long music course. From a methodological perspective, an opening to research on eye movements in music reading was the inclusion of a verbal protocol in the research design: after viewing the musical image, the readers were asked to describe what they had seen. A two-way categorization for verbal descriptions was developed in order to assess the quality of extracted musical information. More extensive musical background was related to shorter average fixation duration, more linear scanning of the musical image, and more sophisticated verbal descriptions of the music in question. No apparent effects of skill development were observed for the novice music readers alone, but all participants improved their verbal descriptions towards the last measurement. Apart from the background-related differences between groups of participants, combining verbal and eye-movement data in a cluster analysis identified three styles of silent reading. The finding demonstrated individual differences in how the freely defined silent-reading task was approached. This dissertation is among the first presentations of a series of experiments systematically addressing the visual processing of music notation in various types of music-reading tasks and focusing especially on the eye-movement indicators of developing music-reading skill. Overall, the experiments demonstrate that the music-reading processes are affected not only by “top-down” factors, such as musical background, but also by the “bottom-up” effects of specific features of music notation, such as pitch heights, metrical division, rhythmic patterns and unexpected melodic events. From a methodological perspective, the experiments emphasize the importance of systematic stimulus design, temporal control during performance tasks, and the development of complementary methods, for easing the interpretation of the eye-movement data. To conclude, this dissertation suggests that advances in comprehending the cognitive aspects of music reading, the nature of expertise in this musical task, and the development of educational tools can be attained through the systematic application of the eye-tracking methodology also in this specific domain.

Fetal alcohol spectrum disorders in Finnish children and adolescents : diagnosis, cognition, behavior, adaptation and brain metabolic alterations

Alcohol consumption during pregnancy can potentially affect the developing fetus in devastating ways, leading to a range of physical, neurological, and behavioral alterations most accurately termed Fetal Alcohol Spectrum Disorders (FASD). Despite the fact that it is a preventable disorder, prenatal alcohol exposure today constitutes a leading cause of intellectual disability in the Western world. In Western countries where prevalence studies have been performed the rates of FASD exceed, for example, autism spectrum disorders, Down’s syndrome and cerebral palsy. In addition to the direct effects of alcohol, children and adolescents with FASD are often exposed to a double burden in life, as their neurological sequelae are accompanied by adverse living surroundings exposing them to further environmental risk. However, children with FASD today remain remarkably underdiagnosed by the health care system. This thesis forms part of a larger multinational research project, The Collaborative Initiative on Fetal Alcohol Spectrum Disorders (the CIFASD), initiated by the National Institute of Alcohol Abuse and Alcoholism (NIAAA) in the U.S.A. The general aim of the present thesis was to examine a cohort of children and adolescents growing up with fetal alcohol-related damage in Finland. The thesis consists of five studies with a broad focus on diagnosis, cognition, behavior, adaptation and brain metabolic alterations in children and adolescents with FASD. The participants consisted of four different groups: one group with histories of prenatal exposure to alcohol, the FASD group; one IQ matched contrast group mostly consisting of children with specific learning disorder (SLD); and two typically-developing control groups (CON1 and CON2). Participants were identified through medical records, random sampling from the Finnish national population registry and email alerts to students. Importantly, the participants in the present studies comprise a group of very carefully clinically characterized children with FASD as the studies were performed in close collaboration with leading experts in the field (Prof. Edward Riley and Prof. Sarah Mattson, Center for Behavioral Teratology, San Diego State University, U.S.A; Prof. Eugene Hoyme, Sanford School of Medicine, University of South Dakota, U.S.A.). In the present thesis, the revised Institute of Medicine diagnostic criteria for FASD were tested on a Finnish population and found to be a reliable tool for differentiating among the subgroups of FASD. A weighted dysmorphology scoring system proved to be a valuable additional adjunct in quantification of growth deficits and dysmorphic features in children with FASD (Study 1). The purpose of Study 2 was to clarify the relationship between alcohol-related dysmorphic features and general cognitive capacity. Results showed a significant correlation between dysmorphic features and cognitive capacity, suggesting that children with more severe growth deficiency and dysmorphic features have more cognitive limitations. This association was, however, only moderate, indicating that physical markers and cognitive capacity not always go hand in hand in individuals with FASD. Behavioral problems in the FASD group proved substantial compared to the typically developing control group. In Study 3 risk and protective factors associated with behavioral problems in the FASD group were explored further focusing on diagnostic and environmental factors. Two groups with elevated risks for behavioral problems emerged: length of time spent in residential care and a low dysmorphology score proved to be the most pervasive risk factor for behavioral problems. The results underscore the clinical importance of appropriate services and care for less visibly alcohol affected children and highlight the need to attend to children with FASD being raised in institutions. With their background of early biological and psychological impairment compounded with less opportunity for a close and continuous caregiver relationship, such children seem to run an especially great risk of adverse life outcomes. Study 4 focused on adaptive abilities such as communication, daily living skills and social skills, in other words skills that are important for gradually enabling an independent life, maintain social relationships and allow the individual to become integrated into society. The results showed that adaptive abilities of children and adolescents growing up with FASD were significantly compromised compared to both typically-developing peers and IQ-matched children with SLD. Clearly different adaptive profiles were revealed where the FASD group performed worse than the SLD group, who in turn performed worse than the CON1 group. Importantly, the SLD group outperformed the FASD group on adaptive behavior in spite of comparable cognitive levels. This is the first study to compare adaptive abilities in a group of children and adolescents with FASD relative to both a contrast group of IQ-matched children with SLD and to a group of typically-developing peers. Finally, in Study 5, through magnetic resonance spectroscopic imaging (MRS) evidence of longstanding neurochemical alterations were observed in adolescents and young adults with FASD related to alcohol exposure in utero 14-20 years earlier. Neurochemical alterations were seen in several brain areas: in frontal and parietal cortices, corpus callosum, thalamus and frontal white matter areas as well as in the cerebellar dentate nucleus. The findings are compatible with neuropsychological findings in FASD. Glial cells seemed to be more affected than neurons. In conclusion, more societal efforts and resources should be focused on recognizing and diagnosing FASD, and supporting subgroups with elevated risk of poor outcome. Without adequate intervention children and adolescents with FASD run a great risk of marginalization and social maladjustment, costly not only to society but also to the lives of the many young people with FASD.

Retrospective study of ocular disorders in Amazon parrots

A retrospective study was conducted to identify the occurrence and types of ocular disorders in 57 Amazon parrots admitted to the Ophthalmology Service, Veterinary Teaching Hospital, School of Veterinary Medicine, University of São Paulo, Brazil from 1997 to 2006. The most frequent observed disorder was cataracts, present in 24 of the 114 examined eyes (57 parrots). Uveitis, ulcerative keratitis and keratoconjunctivitis were frequently diagnosed as well. The cornea was the most affected ocular structure, with 28 reported disorders. Uveal disorders also were commonly observed. Conjunctiva and eyelid disorders were diagnosed in lower frequency. Results suggest that cataracts are common and that cornea, lens and uvea are the most affected ocular structures in Amazon parrots.

Kinematic gait analyses in healthy Golden Retrievers

Kinematic analysis relates to the relative movement between rigid bodies and finds application in gait analysis and other body movements, interpretation of their data when there is change, determines the choice of treatment to be instituted. The objective of this study was to standardize the march of Dog Golden Retriever Healthy to assist in the diagnosis and treatment of musculoskeletal disorders. We used a kinematic analysis system to analyse the gait of seven dogs Golden Retriever, female, aged between 2 and 4 years, weighing 21.5 to 28 kg, clinically normal. Flexion and extension were described for shoulder, elbow, carpal, hip, femorotibialis and tarsal joints. The gait was characterized lateral and had accepted hypothesis of normality for all variables, except for the stance of hip and elbow, considering a confidence level of 95%, significance level α = 0.05. Variations have been attributed to displacement of the stripes during movement and the duplicated number of reviews. The kinematic analysis proved to be a consistent method of evaluation of the movement during canine gait and the data can be used in the diagnosis and evaluation of canine gait in comparison to other studies and treatment of dogs with musculoskeletal disorders.

Rainfall effect on dissipation and movement of diuron and simazine in a vineyard soil

From 2003 to 2007, a field study was performed in a vineyard in Chile to investigate diuron and simazine soil behavior and the effect of additional rainfall. Both herbicides were applied once a year at a rate of 2.0 kg ha-1 a.i. Herbicide concentrations in soil were measured at 0, 10, 20, 40, 90 and 340 days after application, under two pluviometric conditions, natural rainfall and natural rainfall plus irrigation with 180 mm of simulated rainfall during the first 90 days after application. Soil partition coefficient (Kd) varied in the soil profile (0 to 90 cm deep) from 6.75 to 2.04 mL g-1 and from 1.4 to 0.66 mL g-1 and the maximum soil adsorption capacity was approximately 18.3 mg g-1 and 8.3 mg g-1 for diuron and simazine, respectively. Diuron and simazine reached up to 90 and 120 cm of soil depth, with an average of 8.3% and 62.4% of herbicide moved below 15 cm in the soil, respectively. Simazine soil half-life (DT50) was 38.1 days and 7.5 days, whereas the half life for diuron varied from 68.0 and 24.6 for natural rainfall and irrigated, respectively. The average of residual simazine remaining in the whole soil profile after 90 DAA was 25.4% and 39.9% for diuron, with no effect of additional rainfall amount. At 340 DAA the amount of simazine in the whole soil profile corresponded to 13.2% of the initial amount applied, being diuron more persistent with 21.5% of the initial herbicide applied. The high movement in soil of both herbicides could be due to a non-equilibrium sorption process explained by preferential flow, low Kd and high desorption.

Rapid eye movement (REM) sleep deprivation reduces rat frontal cortex acetylcholinesterase (EC 3.1.1.7) activity

Rapid eye movement (REM) sleep deprivation induces several behavioral changes. Among these, a decrease in yawning behavior produced by low doses of cholinergic agonists is observed which indicates a change in brain cholinergic neurotransmission after REM sleep deprivation. Acetylcholinesterase (Achase) controls acetylcholine (Ach) availability in the synaptic cleft. Therefore, altered Achase activity may lead to a change in Ach availability at the receptor level which, in turn, may result in modification of cholinergic neurotransmission. To determine if REM sleep deprivation would change the activity of Achase, male Wistar rats, 3 months old, weighing 250-300 g, were deprived of REM sleep for 96 h by the flower-pot technique (N = 12). Two additional groups, a home-cage control (N = 6) and a large platform control (N = 6), were also used. Achase was measured in the frontal cortex using two different methods to obtain the enzyme activity. One method consisted of the obtention of total (900 g supernatant), membrane-bound (100,000 g pellet) and soluble (100,000 g supernatant) Achase, and the other method consisted of the obtention of a fraction (40,000 g pellet) enriched in synaptic membrane-bound enzyme. In both preparations, REM sleep deprivation induced a significant decrease in rat frontal cortex Achase activity when compared to both home-cage and large platform controls. REM sleep deprivation induced a significant decrease of 16% in the membrane-bound Achase activity (nmol thiocholine formed min-1 mg protein-1) in the 100,000 g pellet enzyme preparation (home-cage group 152.1 ± 5.7, large platform group 152.7 ± 24.9 and REM sleep-deprived group 127.9 ± 13.8). There was no difference in the soluble enzyme activity. REM sleep deprivation also induced a significant decrease of 20% in the enriched synaptic membrane-bound Achase activity (home-cage group 126.4 ± 21.5, large platform group 127.8 ± 20.4, REM sleep-deprived group 102.8 ± 14.2). Our results suggest that REM sleep deprivation changes Ach availability at the level of its receptors through a decrease in Achase activity

Relationship of cytokines and cytokine signaling to immunodeficiency disorders in the mouse

The contributions of cytokines to the development and progression of disease in a mouse model of retrovirus-induced immunodeficiency (MAIDS) are controversial. Some studies have indicated an etiologic role for type 2 cytokines, while others have emphasized the importance of type 1 cytokines. We have used mice deficient in expression of IL-4, IL-10, IL-4 and IL-10, IFN-g, or ICSBP - a transcriptional protein involved in IFN signaling - to examine their contributions to this disorder. Our results demonstrate that expression of type 2 cytokines is an epiphenomenon of infection and that IFN-g is a driving force in disease progression. In addition, exogenously administered IL-12 prevents many manifestations of disease while blocking retrovirus expression. Interruption of the IFN signaling pathways in ICSBP-/- mice blocks induction of MAIDS. Predictably, ICSBP-deficient mice exhibit impaired responses to challenge with several other viruses. This immunodeficiency is associated with impaired production of IFN-g and IL-12. Unexpectedly, however, the ICSBP-/- mice also develop a syndrome with many similarities to chronic myelogenous leukemia in humans. The chronic phase of this disease is followed by a fatal blast crisis characterized by clonal expansions of undifferentiated cells. ICSBP is thus an important determinant of hematopoietic growth and differentiation as well as a prominent signaling molecule for IFNs

Rapid eye movement sleep deprivation induces an increase in acetylcholinesterase activity in discrete rat brain regions

Some upper brainstem cholinergic neurons (pedunculopontine and laterodorsal tegmental nuclei) are involved in the generation of rapid eye movement (REM) sleep and project rostrally to the thalamus and caudally to the medulla oblongata. A previous report showed that 96 h of REM sleep deprivation in rats induced an increase in the activity of brainstem acetylcholinesterase (Achase), the enzyme which inactivates acetylcholine (Ach) in the synaptic cleft. There was no change in the enzyme's activity in the whole brain and cerebrum. The components of the cholinergic synaptic endings (for example, Achase) are not uniformly distributed throughout the discrete regions of the brain. In order to detect possible regional changes we measured Achase activity in several discrete rat brain regions (medulla oblongata, pons, thalamus, striatum, hippocampus and cerebral cortex) after 96 h of REM sleep deprivation. Naive adult male Wistar rats were deprived of REM sleep using the flower-pot technique, while control rats were left in their home cages. Total, membrane-bound and soluble Achase activities (nmol of thiocholine formed min-1 mg protein-1) were assayed photometrically. The results (mean ± SD) obtained showed a statistically significant (Student t-test) increase in total Achase activity in the pons (control: 147.8 ± 12.8, REM sleep-deprived: 169.3 ± 17.4, N = 6 for both groups, P<0.025) and thalamus (control: 167.4 ± 29.0, REM sleep-deprived: 191.9 ± 15.4, N = 6 for both groups, P<0.05). Increases in membrane-bound Achase activity in the pons (control: 171.0 ± 14.7, REM sleep-deprived: 189.5 ± 19.5, N = 6 for both groups, P<0.05) and soluble enzyme activity in the medulla oblongata (control: 147.6 ± 16.3, REM sleep-deprived: 163.8 ± 8.3, N = 6 for both groups, P<0.05) were also observed. There were no statistically significant differences in the enzyme's activity in the other brain regions assayed. The present findings show that the increase in Achase activity induced by REM sleep deprivation was specific to the pons, a brain region where cholinergic neurons involved in REM generation are located, and also to brain regions which receive cholinergic input from the pons (the thalamus and medulla oblongata). During REM sleep extracellular levels of Ach are higher in the pons, medulla oblongata and thalamus. The increase in Achase activity in these brain areas after REM sleep deprivation suggests a higher rate of Ach turnover.

Smoking and psychiatric disorders: a comorbidity survey

Epidemiological and clinical studies have shown a positive correlation between smoking and psychiatric disorders. To investigate the prevalence of cigarette smoking, 277 psychiatric outpatients with anxiety or depressive disorders (DSM-IV) answered a self-evaluation questionnaire about smoking behavior and were compared with a group of 68 control subjects. The diagnoses (N = 262) were: 30.2% (N = 79) major depressive disorder, 23.3% (N = 61) panic disorder, 15.6% (N = 41) social anxiety disorder, 7.3% (N = 19) other anxiety disorders, and 23.7% (N = 62) comorbidity disorders. Among them, 26.3% (N = 69) were smokers, 23.7% (N = 62) were former smokers and 50.0% (N = 131) were nonsmokers. The prevalence of nicotine dependence among the smokers was 59.0% (DSM-IV). The frequency of cigarette smoking did not show any significant difference among the five classes of diagnosis. The social anxiety disorder patients were the heaviest smokers (75.0%), with more unsuccessful attempts to stop smoking (89.0%). The frequency of former smokers was significantly higher among older subjects and nonsmokers were significantly younger (c² = 9.13, d.f. = 2, P = 0.01). Our data present some clinical implications suggesting that in our psychiatric outpatient sample with anxiety disorder, major depression and comorbidity (anxiety disorder and major depression), the frequency of cigarette smoking did not differ from the frequency found in the control group or in general population studies. Some specific features of our population (outpatients, anxiety and depressive disorders) might be responsible for these results.

Functional role of a specific ganglioside in neuronal migration and neurite outgrowth

Cell migration occurs extensively during mammalian brain development and persists in a few regions in the adult brain. Defective migratory behavior of neurons is thought to be the underlying cause of several congenital disorders. Knowledge of the dynamics and molecular mechanisms of neuronal movement could expand our understanding of the normal development of the nervous system as well as help decipher the pathogenesis of neurological developmental disorders. In our studies we have identified and characterized a specific ganglioside (9-O-acetyl GD3) localized to the membrane of neurons and glial cells that is expressed in regions of cell migration and neurite outgrowth in the developing and adult rat nervous system. In the present article we review our findings that demonstrate the functional role of this molecule in neuronal motility.

Use of neuron-specific enolase for assessing the severity and outcome of neurological disorders in patients

Neuron-specific enolase (NSE) is a glycolytic enzyme present almost exclusively in neurons and neuroendocrine cells. NSE levels in cerebrospinal fluid (CSF) are assumed to be useful to estimate neuronal injury and clinical outcome of patients with serious clinical manifestations such as those observed in stroke, head injury, anoxic encephalopathy, encephalitis, brain metastasis, and status epilepticus. We compared levels of NSE in serum (sNSE) and in CSF (cNSE) among four groups: patients with meningitis (N = 11), patients with encephalic injuries associated with impairment of consciousness (ENC, N = 7), patients with neurocysticercosis (N = 25), and normal subjects (N = 8). Albumin was determined in serum and CSF samples, and the albumin quotient was used to estimate blood-brain barrier permeability. The Glasgow Coma Scale score was calculated at the time of lumbar puncture and the Glasgow Outcome Scale (GOS) score was calculated at the time of patient discharge or death. The ENC group had significantly higher cNSE (P = 0.01) and albumin quotient (P = 0.005), but not sNSE (P = 0.14), levels than the other groups (Kruskal-Wallis test). Patients with lower GOS scores had higher cNSE levels (P = 0.035) than patients with favorable outcomes. Our findings indicate that sNSE is not sensitive enough to detect neuronal damage, but cNSE seems to be reliable for assessing patients with considerable neurological insult and cases with adverse outcome. However, one should be cautious about estimating the severity of neurological status as well as outcome based exclusively on cNSE in a single patient.

Clinical and molecular analysis of human reproductive disorders in Brazilian patients

Several genes that influence the development and function of the hypothalamic-pituitary-gonadal-axis (HPG) have been identified. These genes encode an array of transcription factors, matrix proteins, hormones, receptors, and enzymes that are expressed at multiple levels of the HPG. We report the experience of a single Endocrinology Unit in the identification and characterization of naturally occurring mutations in families affected by HPG disorders, including forms of precocious puberty, hypogonadism and abnormal sexual development due to impaired gonadotropin function. Eight distinct genes implicated in HPG function were studied: KAL, SF1, DAX1, GnRH, GnRHR, FSHß, FSHR, and LHR. Most mutations identified in our cohort are described for the first time in literature. New mutations in SF1, DAX1 and GnRHR genes were identified in three Brazilian patients with hypogonadism. Eight boys with luteinizing hormone- (LH) independent precocious puberty due to testotoxicosis were studied, and all have their LH receptor (LHR) defects elucidated. Among the identified LHR molecular defects, three were new activating mutations. In addition, these mutations were frequently associated with new clinical and hormonal aspects, contributing significantly to the knowledge of the molecular basis of reproductive disorders. In conclusion, the naturally occurring genetic mutations described in the Brazilian families studied provide important insights into the regulation of the HPG.

Female pelvic floor disorders – outcome after mesh-augmented procedures and studies on vaginal connective tissue

Pelvic floor disorders, such as urinary incontinence (UI) and pelvic organ prolapse (POP), are common disorders in women. Because of the prolonged life expectancy the prevalence of UI and POP and the probability of ending up in surgery are increasing. However, the pathophysiology behind these disorders is still unsolved. The aim of this thesis is to study possible alterations in the connective tissue in the vaginal wall in patients with and without POP. The long-term outcome and complications of mid-urethral slings (MUS) and mesh-augmented POP surgery were studied in heterogenic patient populations. More elastin and a slight increase in immunostaining of type III and V collagens in tissue samples were obtained from patients with POP compared to controls in whom type I collagen was more prominent. The studies assessing the mesh-augmented procedures revealed good efficacy and high patient satisfaction after a long-term follow-up. Patients operated on because of mixed incontinence and with BMI >30 kg/m² reported significantly more urinary symptoms and a lower quality of life than the patients operated on because of stress urinary incontinence and the ones with BMI ≤30 kg/m². The objective outcome was equal between the groups. Mesh exposure through vaginal mucosa occurred in 23 % of the patients after POP surgery, most of these being asymptomatic. There are alterations in connective tissues in patients with POP. Mid-urethral sling procedures produced good long-term cure rates and patient satisfaction. As to the prolapse surgery, in spite of relatively high exposure rate, mesh-augmented procedure proved to be safe and effective method for the correction of POP.