46,XY disorders of sex development (DSD)

The term disorders of sex development (DSD) includes congenital conditions in which development of chromosomal, gonadal or anatomical sex is atypical. Mutations in genes present in X, Y or autosomal chromosomes can cause abnormalities of testis determination or disorders of sex differentiation leading to 46,XY DSD. Detailed clinical phenotypes allow the identification of new factors that can alter the expression or function of mutated proteins helping to understand new undisclosed biochemical pathways. In this review we present an update on 46,XY DSD aetiology, diagnosis and treatment based on extensive review of the literature and our three decades of experience with these patients.

Growth Hormone Receptor Exon 3 Isoforms and Their Implication in Growth Disorders and Treatment

Human recombinant growth hormone (hGH) has been used to treat short stature in several different conditions, but considerable inter-individual variation in short- and long-term growth response exists. Pharmacogenomics can provide important insights into hGH therapy. The GH receptor (GHR) is the first key molecule mediating GH action. In the past 3 years, a common GHR polymorphism reflecting the presence (GHRf1) or absence (GHRd3) of exon 3 has been under intensive investigation regarding its influence on the response to hGH therapy. Studies that evaluated response to GH treatment determined by these two GHR isoforms in children with GH deficiency, girls with Turner syndrome, children born small for gestational age and patients with acromegaly showed that patients carrying the GHRd3 allele demonstrated a greater GH sensitivity than patients homozygous for the GHRf1 allele. Other studies presented contradictory data, however, which may be caused by confounding factors such as small sample sizes and differences in experimental design. This GHR exon 3 genotype is the first identified genetic factor found to modulate the individual response to GH therapy. This article reviews the historical aspects and pharmacogenetic studies published to date in relation to this GHR polymorphism. The analyses of present and future validation studies may define the use of this and other polymorphisms in clinical practice, moving from pharmacogenetics to routine application and allowing individualization of hGH doses to optimize final outcome. Copyright (C) 2009 S. Karger AG, Basel

Anxiety Disorders and Rheumatic Fever: Is There an Association?

Introduction: Findings suggest that obsessive-compulsi e disorder (OCD) and related disorders, referred to as obsessive-compulsive spectrum disorders (OCSDs), are more common in patients with rheumatic fever (RF). Objectives: To determine whether RF or Sydenham`s chorea increases the probability of anxiety disorders in the relatives of individuals with RF with and without SC. Methods: This was a case-Control family study in which 98 probands and 389 first-degree relatives (FDRs) were assessed using structured psychiatric interviews. A Poisson regression model was used to determine whether the presence of any disorder in one family member influences the rate of disorders in the remaining family members. Results: Generalized anxiety disorder (GAD) occurred more frequently in the FDRs of RF probands than in those of control probands (P=.018). The presence of RF,GAD, or separation anxiety disorder in one family member significantly increased the chance of OCSDs in another member of the family.

Visuospatial processing and the function of prefrontal-parietal networks in autism spectrum disorders: a functional MRI study

Objective: Individuals with autism spectrum disorders typically have normal visuospatial abilities but impaired executive functioning, particularly in abilities related to working memory and attention. The aim of this study was to elucidate the functioning of frontoparietal networks underlying spatial working memory processes during mental rotation in persons with autism spectrum disorders. Method: Seven adolescent males with normal IQ with an autism spectrum disorder and nine age- and IQ-matched male comparison subjects underwent functional magnetic resonance imaging scans while performing a mental rotation task. Results: The autism spectrum disorders group showed less activation in lateral and medial premotor cortex, dorsolateral prefrontal cortex, anterior cingulate gyrus, and caudate nucleus. Conclusions: The finding of less activation in prefrontal regions but not in parietal regions supports a model of dysfunction of frontostriatal networks in autism spectrum disorders.

Psychoses of epilepsy: A study comparing the clinical features of patients with focal versus generalized epilepsies

In the literature, psychosis of epilepsy (POE) has been described as one of the most frequent psychiatric comorbidities of epilepsy, occurring particularly in association with temporal lobe epilepsy. However, the presence of such psychiatric disorders among patients with idiopathic generalized epilepsies has also been mentioned. In this study, we evaluated the clinical features of psychotic disorders in a series of patients with temporal lobe epilepsy related to mesial temporal sclerosis (TLE-MTS) and juvenile myoclonic epilepsy with the aim of describing and comparing the clinical patterns of the psychotic symptoms in such frequent and important epilepsy syndromes. POE occurred most frequently in patients with TLE-MTS (P=0.01), but no differences were observed between the groups with respect to the subtypes and core symptoms of psychoses. The clinical implications of POE in both epilepsy syndromes are discussed. (C) 2011 Elsevier Inc. All rights reserved.

Carbamazepine can induce kidney water absorption by increasing aquaporin 2 expression

Background. Carbamazepine (Carba) is an anticonvulsant and psychotropic drug used widely for the treatment of intellectual disability and severe pains, but the incidence of hyponatremia is a common related occurrence. This hyponatremia is frequently attributed to a SIADH induced by this drug. It is also known that Carba is used to decrease the urinary volume in Diabetes Insipidus (DI) because it has an antidiuretic effect. Lithium (Li) is one of the most important drugs used to treat bipolar mood disorders. However Li has the undesirable capacity to induce DI. Nowadays, the association of these drugs is used in the treatment of patients with psychiatric and neurological problems. Methods. In vivo and in vitro (microperfusion) experiments were developed to investigate the effect of Carba in the rat Inner Medullary Collecting Duct (IMCD). Results. The results revealed that Carba was able to stimulate the V2 vasopressin receptor-Protein G complex increasing the water permeability (Pf) and water absorption. In vivo studies showed that in rats with lithium-induced DI, Carba decreased the urinary volume and increased the urinary osmolality. AQP2 expression was increased both in normal IMCD incubated with Carba and in IMCD from lithium-induced DI after Carba addition to the diet, when compared with the control. Conclusion. These results showed that the hyponatremia observed in patients using this anticonvulsant drug, at least in part, is due to the Carba capacity to increase IMCD`s Pf and that the Lithium-Carbamazepine association is beneficial to the patient.

Outcomes after multi-modality treatment of musculoskeletal tumours

Outcomes of treatment of musculoskeletal tumours are evaluated for effectiveness of chemotherapy protocols, function obtained after surgery and survival after treatment. Quality of life achieved after multi-modality treatment is dependent on a combination of all of these factors. Quality of life varies significantly along the treatment pathway, and continuously through the life of a patient. The patient's perception of outcome is based on the total effect of the disease and its treatment, rather than necessarily focussing on separate items of treatment. We have found that visual analogue scales can be used effectively to gauge the patient's perception of their quality of life. Such a method has shown that, overall, perceptions of quality of life seem to be better for those patients who have undergone successful limb salvage surgery when compared with those who have undergone amputation, but the differences are not as great as might be assumed.

Mutations of the thyroglobulin gene and its relevance to thyroid disorders

Purpose of review To perform an update review on thyroglobulin gene mutations associated with congenital hypothyroidism, thyroid cancer, and autoimmunity. Recent findings Forty-two thyroglobulin mutations have been identified in dyshormonogenetic congenital hypothyroidism. Clinical and laboratory criteria defining defective thyroglobulin synthesis are mostly related to thyroglobulin mutations, generally caused by intracellular thyroglobulin transport defects to the colloid rather than defects in thyroid hormones synthesis. Some mutated thyroglobulin may escape the rigorous chaperone control and reach the colloid, allowing a wide phenotypic spectrum that includes euthyroidism in an adequate iodine environment. In some patients, continuous levothyroxine treatment does not reduce elevated serum thyroid-stimulating hormone (TSH) levels that may lead to goiter development. Prenatally, inactive mutant thyroglobulin will not be able to synthesize thyroid hormones and may increase pituitary thyrotroph threshold for thyroid hormone feedback. Congenital goiter is a risk factor for thyroid cancer and some thyroglobulin variants may confer susceptibility to thyroid autoimmunity. Summary Advances in the understanding of thyroglobulin genetic defects and its severity should allow researchers to perform adequate molecular diagnosis, genetic counseling, and intrauterine treatment to prevent subtle deficits in central nervous system development. This knowledge should improve the understanding of physiological functions of the thyroid and influence of nutritional iodine.

Thyroid and the environment: exposure to excessive nutritional iodine increases the prevalence of thyroid disorders in Sao Paulo, Brazil

Objective: To evaluate the prevalence of chronic autoimmune thyroiditis (CAT) and iodine-induced hypothyroidism, hyperthyroidism (overt and subclinical). and goiter in a population exposed to excessive iodine intake for 5 years (table salt iodine concentrations: 40-100 mg/kg salt). Design: This was a population-based, cross-sectional study with 1085 participants randomly selected from a metropolitan area in Sao Paulo, Brazil, and conducted during the first semester of 2004. Methods: Thyroid ultrasound examination was performed in all participants and samples of urine and blood were collected from each subject. Serum levels of thyroid-stimulating hormone, free thyroxine, and anti-thyroid peroxidase (TPO) antibodies, urinary iodine concentration. thyroid volume, and thyroid echogenicity were evaluated. We also analyzed table salt iodine concentrations. Results: At the time the study was conducted, table salt iodine concentrations were within the new official limits (20-60 mg/kg salt). Nevertheless, in 45.6%, of the participants, urinary iodine excretion was excessive (above 300 mu g/l) and, in 14.1%, it was higher than 400 mu g/l. The prevalence of CAT (including atrophic thyroiditis) was 16.9% (183/1085), women were more affected than men (21.5 vs 9.1% respectively, P=0.02). Hypothyroidism was detected in 8.0%, (87/1085) of the Population with CAT. Hyperthyroidism was diagnosed in 3.3% of the individuals (36/1085) and goiter was identified in 3.1% (34/1085). Conclusions: Five years of excessive iodine intake by the Brazilian population may have increased the prevalence of CAT and hypothyroidism in subjects genetically predisposed to thyroid autoimmune diseases. Appropriate screening for early detection of thyroid dysfunction may be considered during excessive nutritional iodine intake.

Empirically validated interventions for adult disorders

The movement towards evidence-based practice in psychology and medicine should offer few problems in cognitive-behaviour therapies because it is consistent with the principles by which they have been developed and disseminated. However, the criteria for assessing empirical status, including the heavy emphasis on manualised treatments, need close examination. A possible outcome of the evidence-based movement would be to focus on the application of manualised treatments in both training and clinical practice; problems with that approach are discussed. If we are committed to evidence-based treatment, comparisons between psychological and pharmacological interventions should also be included so that rational health care decisions can be made. We should not be afraid of following the evidence, even when it supports treatments that are not cognitive-behavioural in stated orientation. Such results should be taken as an opportunity for theoretical development and new empirical inquiry rather than be a cause for concern.

Enhancing the phonological processing skills of children with specific reading disability

The present study evaluated the benefits of phonological processing skills training for children with persistent reading difficulties. Children aged between 9-14 years, identified as having a specific reading disability, participated in the study. In a series of three experiments, pedagogical issues related to length of training time, model of intervention and severity of readers' phonological processing skills deficit prior to intervention, were explored. The results indicated that improvement in poor readers' phonological processing skills led to a dramatic improvement in their reading accuracy and reading comprehension performance. Increasing the length of training time significantly improved transfer effects to the reading process. Children with particularly severe phonological processing skill deficits benefited from art extended training period, and both individual and group intervention models for phonological processing training proved successful. Implications for speech and language therapists are discussed.

Social adaptation of children with mild intellectual disability: Effects of partial integration within primary school classes

is study examined the social adaptation of children with mild intellectual disability who were either (a) partially integrated into regular primary school classes, or (b) full-time in separate classes, All of the children were integrated in sport and play activities with the whole school. Consistent with previous research, children with intellectual disability were less socially accepted than were a matched group of control children. Children in partially integrated classes received more play nominations than those in separate classes, brit there was no greater acceptance as a best friend. On teachers' reports, disabled children had higher levels of inappropriate social behaviours, but there was no significant difference in appropriate behaviours. Self-assessments by integrated children were more negative than those by children in separate classes, and their peer-relationship satisfaction was lower. Ratings by disabled children of their satisfaction with peer relationships were associated with ratings of appropriate social skills by themselves and their teachers, and with self-ratings of negative behaviour. The study confirmed that partial integration can have negative consequences for children with an intellectual disability.

Prevalence of fibromyalgia and chronic widespread pain in community-dwelling elderly subjects living in Sao Paulo, Brazil

Objectives: To estimate the prevalence of fibromyalgia (FM) and chronic widespread pain (CWP) in community-dwelling elderly individuals living in Sao Paulo, to assess the spectrum of problems related to these diseases using the Fibromyalgia Impact Questionnaire (FIQ) and to correlate the FIQ with the number of tender points and with pain threshold. Methods: Our sample consisted of 361 individuals (64% women, 36% men, mean age of 73.3 +/- 5.7 years). Individuals were classified into four groups: FM (according to American College of Rheumatology criteria), CWP, regional pain (RP) and no pain (NP). Pain characteristics and dolorimetry for 18 tender points and the FIQ were assessed. Results: The prevalence of FM was 5.5% [95% confidence interval (CI) = 5.4-5.7], and the prevalence of CWP was 14.1% (95% Cl: 10.5-17.7%). The frequency of RP was 52.6% and the prevalence of NP was 27.7%. FIQ scores were higher in people with FM (44.5), followed by CWP (31.4), RP (18.1) and NP (5.5) (p < 0.001). There was a positive correlation between the domains of the FIQ and the number of tender Points (p < 0.05), and a negative correlation between FIQ score and pain threshold (p < 0.05). Conclusion: In our elderly subjects, the prevalence of FM was slightly higher compared to previously reported studies, and CWP was around 14%. The spectrum of problems related to chronic pain was more severe in FM followed by CWP, strongly suggesting that these conditions should be diagnosed and adequately treated in older individuals. (C) 2010 Elsevier Ireland Ltd. All rights reserved.