Alcohol use disorders in patients with obsessive-compulsive disorder: The importance of appropriate dual-diagnosis

Objective: To evaluate the prevalence and clinical associated factors of alcohol use disorders (AUD) comorbidity in a large clinical sample of patients with obsessive-compulsive disorder (OCD). Methods: A cross-sectional study including 630 DSM-IV OCD patients from seven Brazilian university services, comparing patients with and without AUD comorbidity. The instruments of assessment used were a demographic and clinical questionnaire including evaluation of suicidal thoughts and acts and psychiatric treatment, the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I), the Yale-Brown Obsessive-Compulsive Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, the Brown Assessment of Beliefs Scale, the Beck Depression and Anxiety Inventories and the Clinical Global Impression Scale. Current or past alcohol and other psychoactive substances use, abuse and dependence were assessed using the SCID-I (section E) and corroborated by medical and familial history questionnaires. Results: Forty-seven patients (7.5%) presented AUD comorbidity. Compared to OCD patients without this comorbidity they were more likely to be men, to have received previous psychiatric treatment, to present: lifetime suicidal thoughts and attempts and to have higher scores in the hoarding dimension. They also presented higher comorbidity with generalized anxiety and somatization disorders, and compulsive sexual behavior. Substance use was related to the appearance of the first O.C. symptoms and symptom amelioration. Conclusions: Although uncommon among OCD treatment seeking samples, AUD comorbidity has specific clinical features, such as increased risk for suicidality, which deserve special attention from mental health professionals. Future studies focused on the development of specific interventions for these patients are warranted. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

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

Spectrum of MMACHC mutations in Italian and Portuguese patients with combined methylmalonic aciduria and homocystinuria, cblC type

Methylmalonic aciduria (MMA) and homocystinuria, cblC type (MIM 277400) is the most frequent inborn error of vitamin B-12. The recent identification of the disease gene, MMACHC, has permitted preliminary genotype-phenotype correlations. We studied 24 Italian and 17 Portuguese patients with cblC defect to illustrate the spectrum of mutations in a southern European population and discuss the impact that mutation identification has on routine diagnostic procedures. Since the metabolic defect raises the serum levels of homocysteine, we also tested if variants in MTHFR-playing a key role in homocysteine remethylation pathway-could act as genetic modifier in cblC defect. We found that the c.271 dupA (accounting for 55% of the MMA CH alleles in our cohort) followed by c.394C > T (16%) and c.331C > T (9%) were the most frequent mutations. In our study we also identified a novel mutation (c.544T > C). On the other hand, the MTHFR genotype did not appear to influence age at onset, the clinical phenotype and outcome of patients with cblC defect. This study shows that mutation screening for the most common MMACH mutations occurring in early-onset forms (c.271dupA and c.331C > T) seems to have a high diagnostic yield in a southern European population with cblC defect. Although the identification of the gene defect per se does not predict completely time and severity of disease appearance, our data corroborate the importance of a molecular testing to offer accurate prenatal diagnosis to couples at high risk of having affected children. (C) 2007 Elsevier Inc. All rights reserved.

On the spectrum for K_{m+2}/K_m designs

The spectrum problem for the decomposition of K-n into copies of the graph K_{m+2}\K_m is solved for n = 0 or 1 (mod 2m + 1). (C) 1997 John Wiley & Sons, Inc.

The Parkes half-jansky flat-spectrum sample

We present a new sample of Parkes half-jansky flat-spectrum radio sources, having made a particular effort to find any previously unidentified sources. The sample contains 323 sources selected according to a flux limit of 0.5 Jy at 2.7 GHz, a spectral index measured between 2.7 and 5.0 GHz of alpha(2.7/5.0) > -0.5, where S(nu) proportional to nu(alpha), Galactic latitude \b\ > 20 degrees and -45 degrees < declination (B1950) < +10 degrees. The sample was selected from a region 3.90 steradians in area. We have obtained accurate radio positions for all the unresolved sources in this sample, and combined these with accurate optical positions from digitized photographic sky survey data to check all the optical identifications. We report new identifications based on R- and Kn-band imaging and new spectroscopic measurements of many of the sources. We present a catalogue of the 323 sources, of which 321 now have identified optical counterparts and 277 have measured spectral redshifts.

Resonance fluorescence spectrum of a two-level atom driven by a bichromatic field in a squeezed vacuum

The steady-state resonance fluorescence spectrum of a two-level atom driven by a bichromatic field in a broadband squeezed vacuum is studied. When the carrier frequency of the squeezed vacuum is tuned to the frequency of the central spectral line, anomalous spectral features, such as hole burning and dispersive profiles, can occur at the central line. We show that these features appear for wider, and experimentally more convenient, ranges of the parameters than in the case of monochromatic excitation. ?he absence of a coherent spectral component at the central line makes any experimental attempt to observe these features much easier. We also discuss the general features of the spectrum. When the carrier frequency of the squeezed vacuum is tuned to the first odd or even sidebands, the spectrum is asymmetric and only the sidebands an sensitive to phase. For appropriate choices of the phase the linewidths or only the odd or even sidebands can be reduced. A dressed-stale interpretation is provided.

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.

Spectrum and Prevalence of FP/TMEM127 Gene Mutations in Pheochromocytomas and Paragangliomas

Context Pheochromocytomas and paragangliomas are genetically heterogeneous neural crest-derived neoplasms. We recently identified germline mutations of the novel transmembrane-encoding gene FP/TMEM127 in familial and sporadic pheochromocytomas consistent with a tumor suppressor effect. Objectives To examine the prevalence and spectrum of FP/TMEM127 mutations in pheochromocytomas and paragangliomas and to test the effect of mutations in vitro. Design, Setting, and Participants We sequenced the FP/TMEM127 gene in 990 individuals with pheochromocytomas and/or paragangliomas, including 898 previously unreported cases without mutations in other susceptibility genes from 8 independent worldwide referral centers between January 2009 and June 2010. A multiplex polymerase chain reaction-based method was developed to screen for large gene deletions in 545 of these samples. Confocal microscopy of 5 transfected mutant proteins was used to determine their subcellular localization. Main Outcome Measures The frequency and type of FP/TMEM127 mutation or deletion was assessed and correlated with clinical variables; the subcellular localization of 5 overexpressed mutants was compared with wild-type FP/TMEM127 protein. Results We identified 19 potentially pathogenic FP/TMEM127 germline mutations in 20 independent families, but no large deletions were detected. All mutation carriers had adrenal tumors, including 7 bilateral (P=2.7 x 10(-4)) and/or with familial disease (5 of 20 samples; P=.005). The median age at disease onset in the FP/TMEM127 mutation group was similar to that of patients without a mutation (41.5 vs 45 years, respectively; P=.54). The most common presentation was that of a single benign adrenal tumor in patients older than 40 years. Malignancy was seen in 1 mutation carrier (5%). Expression of 5 novel FP/TMEM127 mutations in cell lines revealed diffuse localization of the mutant proteins in contrast with the discrete multiorganelle distribution of wild-type TMEM127. Conclusions Germline mutations of FP/TMEM127 were associated with pheochromocytoma but not paraganglioma and occured in an age group frequently excluded from genetic screening algorithms. Disease-associated mutations disrupt intracellular distribution of the FP/TMEM127 protein. JAMA. 2010;304(23):2611-2619 www.jama.com

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.

Isotopically resolved (B)over-tilde<-(X)over-tilde electronic spectrum of Ag-3 and calculation of its Jahn-Teller effects

Ag-3 was produced by pulsed-nozzle laser vaporisation and jet-cooled in a Ne supersonic expansion. One-color resonant two-photon ionisation (R2PI) spectra of the (B) over tilde(2) E '' <-- (X) over tilde(2) E' transition of Ag-3 were separately measured for all four isotopic combinations. Long vibrational progressions are observed, involving clearly resolved bands at low energy, merging into a dense but resolvable spectrum up to 1000 cm(-1) above the origin. Both the ground (X) over tilde(2) E' and excited (B) over tilde(2) E '' states of Ag-3 are susceptible to Jahn-Teller distortion along the degenerate e' bending coordinate. The Jahn-Teller analysis includes both linear and quadratic terms, simultaneously with the spin-orbit coupling. Following extensive parameter fitting, the absorption spectrum is calculated, and bands assigned. The spin-orbit splitting is quenched below the localization energy, but becomes observable approximate to 300 cm(-1) above the origin.

A novel TBX5 missense mutation (V263M) in a family with atrial septal defects and postaxial hexodactyly

Background: Congenital heart diseases are the most frequent birth defects and are commonly associated with skeletal malformations. Mutations in the TBX5 gene, a T-box transcription factor located on chromosome 12q24.1, have been demonstrated to be the underlying molecular alteration in individuals with different congenital cardiac disorders, notably the Holt-Oram syndrome. Methods: Six members from a two-generation family from a consanguineous couple, which had atrial septal defects associated with postaxial hexodactyly in all extremities were clinically assessed and submitted to TBX5 mutational analysis performed by direct sequencing. Results: We detected a new TBX5 missense mutation (V263M) in all four individuals studied with cardiac abnormalities. The genotype phenotype correlations in light of unusual features are extensively discussed, as well as the possible significance of these atypical findings. Conclusions: These new data extend our clinical and molecular knowledge of TBX5 gene mutations and also raise interesting questions about the phenotype heterogeneity regarding these gene alterations. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Comorbidity of mental disorders with substance misuse

The title of this editorial evokes the image of a patient with a psychosis, usually schizo phrenia, who abuses or is dependent upon alcohol or an illicit drug. The suffering of these individuals and their families is un deniable, as are the difficulties that mental health and addiction services face in helping them. None the less, this form of comorbid ity has overshadowed more prevalent and remediable patterns of comorbidity between substance misuse and mental disorders (Hall, 1996).

Non-alcoholic Wernicke`s encephalopathy: broadening the clinicoradiological spectrum

Wernicke`s encephalopathy (WE) is a serious neurological disorder secondary to thiamine deficiency. Improved recognition by radiologists and allied health providers of the different clinical settings and imaging findings associated with this emergency can optimise the management of this condition and help prevent its severe consequences. The aim of this study is to illustrate the broad clinicoradiological spectrum of non-alcoholic WE, while emphasising atypical MRI findings.

Frequency of concurrent autoimmune disorders in patients with autoimmune hepatitis - Effect of age, gender, and genetic background

Background: Concurrent autoimmune disorders (CAIDs) have been shown to occur in 22% to 34% of the patients with autoimmune hepatitis (AIH). Their presence has been linked to female gender, older age, and to certain HLA antigens, namely HLA-A11. DRB1*04, and DRB4*01. Aims: To assess the frequency and nature of CAID in Brazilian patients with AIH types 1 (AIH-1) and 2 (AIH-2) and to investigate the influence of age, gender, and genetic background in their occurrence. Patients and Methods: The presence and nature of CAID was studied in 143 patients [117 females, median age 11 (1.3 to 69)] with AIH-1 (n = 125) and AIH-2 (n = 28). HLA typing and tumor necrosis factor a gene promoter and exon I cytotoxic T lymphocyte associated antigen 4 (CTLA-4) gene polymorphisms were determined by polymerase chain reaction-based techniques. Results: The frequency of CAID was similar in patients with AIH-1 (14%) and AIH-2 (18%), but their nature was shown to vary. Arthritis was seen in half of the patients (n = 8) with CAID and AIH-1 and in none of those with AIH-2. Subjects with AIH-1 and CAID were shown to be older [24 (1.3 to 6 1) vs. 11 (1.3 to 69) y P = 0.02] and to have more often circulating antinuclear antibody (76% vs. 40%, P = 0.008) and less frequently antiactin antibodies (33% vs. 75%, P = 0.008) when compared with their counterparts without CAID. No particular HLA-DR and DQ alleles, as well as tumor necrosis factor a and CTLA-4 genotypes, were associated with CAID. Conclusions: The nature, but not the frequency, of CAID was shown to vary in AIH-1 and AIH-2. In subjects with AIH-1, CAID was linked to older subjects and to the presence of antinuclear antibody. No predisposition to CAID was associated to HLA-DRB1*04 or DDB4*01 alleles. The observed lower frequency of CAID could be attributed to the lower age of disease onset in Brazilians and to differences in HLA-encoded susceptibility to AIH-1 observed in South America.