Ultrasound detection rate of single umbilical artery in the first trimester of pregnancy

Objective To determine accuracy of first trimester detection of single umbilical artery (SUA). Methods The number of vessels in the umbilical cord was examined in a prospective cohort of 779 singleton, low-risk, unselected pregnancies, in the first (11-13 weeks) and second (17-24 weeks) trimesters, using both power and color Doppler and after delivery, by placental histopathologic exam. Concordance between first and second trimester findings to postnatal diagnoses was compared by calculating kappa coefficients. Results There was medium concordance between the findings in the first trimester and the postnatal diagnoses (kappa = 0.52) and high concordance (kappa = 0.89) for the second trimester scan. Sensitivity, specificity, positive and negative predictive values for the findings in the first trimester were 57.1, 98.9, 50.0 and 99.2% and for the second trimester were 86.6, 99.9, 92.9 and 99.7%. Conclusion Sensitivity and positive predictive value of first trimester scan to identify an isolated SUA in a prospective unselected population was poor. Diagnosis of isolated SUA as well as a definitive judgment about the presence of associated anomalies would still require a scan in the second trimester. Copyright (C) 2011 John Wiley & Sons, Ltd.

Intrauterine Growth Restriction and Zinc Concentrations in Term Infants during the First Month of Life

Objective: We analyzed the influence of IUGR on the concentrations of plasma (Znpl) and erythrocyte (Zne) zinc and on the ratios of Zne to Znpl (Zne:Znpl) and Zne to hemoglobin (Zne:Hb) in term infants during the first month of life. Design: Cohort study. Setting: Tertiary Care Neonatal Unit. Subjects: Exclusively breastfed term newborns (n = 84) were divided into 3 groups: group 1, without IUGR (n = 41), group II. with mild to moderate IUGR (n = 12). and group III, with severe IUGR (n = 31). IUGR was defined as birth weight under the 5th percentile of the Alexander et at curve and as a Kramer Index (KI: ratio of birth weight to estimated weight for each gestational age) <0.85. Severe IUGR was defined as a KI <0.75. Znpl, Zne. and Hb were measured at birth. 3 days, and 1 month of life. Results: Znpl tended to decrease (P = 0.073), Zne and Zne:Znpl increased (P < 0.001), and Hb decreased (P < 0.001) during the first month of life. There was not Znpl, Zne and Zne:Znpl time by group interaction. Zne:Hb increased (P < 0.001) during the first month of life and was lower in Group II at I month of age. Differences between Groups I and If (P = 0.017) and Groups II and III at I month of age (P = 0.011) were detected. Conclusions: Our results suggest that IUGR did not have association with erythrocyte zinc and Zne:Hb ratio at birth. However. neonatal nutrition could have influenced zinc incorporation during this period, through Zne increase.

Phenotype-genotype analysis of cryopyrin-associated periodic syndromes (CAPS): Description of a rare non-exon 3 and a novel CIAS1 missense mutation

We describe in this paper the phenotype-genotype analysis of a Brazilian cohort of patients with cryopyrin-associated periodic syndromes (CAPS). Patient 1 presented with an urticarial rash and recurrent fever exacerbated by cold weather, arthritis, and anterior uveitis, thus, receiving a clinical diagnosis of familial cold autoinflammatory syndrome. CIAS1 sequencing identified the T436I mutation, previously associated to a clinical phenotype of chronic infantile neurological cutaneous and articular/neonatal onset multisystem inflammatory disease. Patient 2 developed a papular exanthema with daily fever shortly after birth, frontal bossing, patellae enlargement, and cognitive and motor impairments. Sequencing identified the exceedingly rare G755R CIAS1 mutation in exon 4. Patient 3 developed skin rash and articular symptoms 6 h after birth, followed by aseptic meningitis. He was found to have the novel C148Y missense mutation in CIAS1. This report expands the spectrum of CIAS1 mutations associated to clinical disease, suggests that the same mutation can be associated with different clinical syndromes, and supports the evidence that CAPS patients should always be screened for mutations outside exon 3.

A population-based morphometric MRI study in patients with first-episode psychotic bipolar disorder: comparison with geographically matched healthy controls and major depressive disorder subjects

Objectives: Many morphometric magnetic resonance imaging (MRI) studies that have investigated the presence of gray matter (GM) volume abnormalities associated with the diagnosis of bipolar disorder (BD) have reported conflicting findings. None of these studies has compared patients with recent-onset psychotic BD with asymptomatic controls selected from exactly the same environment using epidemiological methods, or has directly contrasted BD patients against subjects with first-onset psychotic major depressive disorder (MDD). We examined structural brain differences between (i) BD (type I) subjects and MDD subjects with psychotic features in their first contact with the healthcare system in Brazil, and (ii) these two mood disorder groups relative to a sample of geographically matched asymptomatic controls. Methods: A total of 26 BD subjects, 20 subjects with MDD, and 94 healthy controls were examined using either of two identical MRI scanners and acquisition protocols. Diagnoses were based on DSM-IV criteria and confirmed one year after brain scanning. Image processing was conducted using voxel-based morphometry. Results: The BD group showed increased volume of the right dorsal anterior cingulate cortex relative to controls, while the MDD subjects exhibited bilateral foci GM deficits in the dorsolateral prefrontal cortex (p < 0.05, corrected for multiple comparisons). Direct comparison between BD and MDD patients showed a focus of GM reduction in the right-sided dorsolateral prefrontal cortex (p < 0.05, corrected for multiple comparisons) and a trend (p < 0.10, corrected) toward left-sided GM deficits in the dorsolateral prefrontal cortex of MDD patients. When analyses were repeated with scanner site as a confounding covariate the finding of increased right anterior cingulate volumes in BD patients relative to controls remained statistically significant (p = 0.01, corrected for multiple comparisons). Conclusions: These findings reinforce the view that there are important pathophysiological distinctions between BD and MDD, and indicate that subtle dorsal anterior cingulate abnormalities may be relevant to the pathophysiology of BD.

Time to rehospitalization in patients with schizophrenia discharged on first generation antipsychotics, non-clozapine second generation antipsychotics, or clozapine

Rehospitalization is an important outcome of drug effectiveness in schizophrenia. In this study, the hypothesis that clozapine and some second generation antipsychotics (SGA) were superior to first generation antipsychotics (FGA) in preventing rehospitalization of patients with schizophrenia discharged from a university hospital in Brazil was tested. A retrospective observational study was conducted designed to evaluate time to rehospitalization of patients with schizophrenia discharged on a regimen of oral FGA, depot FGA, risperidone, olanzapine and amisulpride, other SGA, or clozapine, during a three-year follow-up period. Risk factors associated with rehospitalization were examined. Of the 464 patients with schizophrenia discharged from hospital, 242 met criteria for study entry. Higher rehospitalization rates were observed in patients treated with depot FGA (30%), risperidone (30%) and other SGA groups (28.5%), respectively. Clozapine was significantly associated with lower rehospitalization risk compared with risperidone. The risk of rehospitalization in patients on olanzapine and amisulpride, and oral FGA, was similar to that of patients in use of clozapine. These results however, are limited by the heterogeneity of illness severity across the groups. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Lack of progression of brain abnormalities in first-episode psychosis: a longitudinal magnetic resonance imaging study

Background. Some neuroimaging studies have supported the hypothesis of progressive brain changes after a first episode of psychosis. We aimed to determine whether (i) first-episode psychosis patients would exhibit more pronounced brain volumetric changes than controls over time and (ii) illness course/treatment would relate to those changes. Method. Longitudinal regional grey matter volume and ventricle : brain ratio differences between 39 patients with first-episode psychosis (including schizophrenia and schizophreniform disorder) and 52 non-psychotic controls enrolled in a population-based case-control study. Results. While there was no longitudinal difference in ventricle : brain ratios between first-episode psychosis subjects and controls, patients exhibited grey matter volume changes, indicating a reversible course in the superior temporal cortex and hippocampus compared with controls. A remitting course was related to reversal of baseline temporal grey matter deficits. Conclusions. Our findings do not support the hypothesis of brain changes indicating a progressive course in the initial phase of psychosis. Rather, some brain volume abnormalities may be reversible, possibly associated with a better illness course.

Lateral ventricle differences between first-episode schizophrenia and first-episode psychotic bipolar disorder: A population-based morphometric MRI study

Objectives. The extent to which psychotic disorders fall into distinct diagnostic categories or can be regarded as lying on a single continuum is controversial. We compared lateral ventricle volumes between a large sample of patients with first-episode schizophrenia or bipolar disorder and a healthy control group from the same neighbourhood. Methods. Population-based MRI study with 88 first-episode psychosis (FEP) patients, grouped into those with schizophrenia/schizophreniform disorder (N = 62), bipolar disorder (N = 26) and 94 controls. Results. Right and left lateral ventricular and right temporal horn volumes were larger in FEP subjects than controls. Within the FEP sample, post-hoc tests revealed larger left lateral ventricles and larger right and left temporal horns in schizophrenia subjects relative to controls, while there was no difference between patients with bipolar disorder and controls. None of the findings was attributable to effects of antipsychotics. Conclusions. This large-sample population-based MRI study showed that neuroanatomical abnormalities in subjects with schizophrenia relative to controls from the same neighbourhood are evident at the first episode of illness, but are not detectable in bipolar disorder patients. These data are consistent with a model of psychosis in which early brain insults of neurodevelopmental origin are more relevant to schizophrenia than to bipolar disorder.

Cognitive performance is related to cortical grey matter volumes in early stages of schizophrenia: A population-based study of first-episode psychosis

Background: Neuropsychological deficits have been reported in association with first-episode psychosis (FEP). Reductions in grey matter (GM) volumes have been documented in FEP subjects compared to healthy controls. However, the possible inter-relationship between the findings of those two lines of research has been scarcely investigated. Objective: To investigate the relationship between neuropsychological deficits and GM volume abnormalities in a population-based sample of FEP patients compared to healthy controls from the same geographical area. Methods: FEP patients (n = 88) and control subjects (n = 86) were evaluated by neuropsychological assessment (Controlled Oral Word Association Test, forward and backward digit span tests) and magnetic resonance imaging using voxel-based morphometry. Results: Single-group analyses showed that prefrontal and temporo-parietal GM volumes correlated significantly (p < 0.05, corrected) with cognitive performance in FEP patients. A similar pattern of direct correlations between neocortical GM volumes and cognitive impairment was seen in the schizophrenia subgroup (n = 48). In the control group, cognitive performance was directly correlated with GM volume in the right dorsal anterior cingulate cortex and inversely correlated with parahippocampal gyral volumes bilaterally. Interaction analyses with ""group status"" as a predictor variable showed significantly greater positive correlation within the left inferior prefrontal cortex (BA46) in the FEP group relative to controls, and significantly greater negative correlation within the left parahippocampal gyrus in the control group relative to FEP patients. Conclusion: Our results indicate that cognitive deficits are directly related to brain volume abnormalities in frontal and temporo-parietal cortices in FEP subjects, most specifically in inferior portions of the dorsolateral prefrontal cortex. (C) 2009 Elsevier B.V. All rights reserved.

Association of the UGT1A1-53(TA)(n) polymorphism with L-thyroxine doses required for thyrotropin suppression in patients with differentiated thyroid cancer

There is a considerable interindividual variation in L-thyroxine [ 3,5,3`,5`-tetraiodo-l-thyronine (T(4))] dose required for thyrotropin (thyroid-stimulating hormone) suppression in patients with differentiated thyroid cancer. To investigate whether uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)-mediated T(4) glucuronidation in liver affects T(4) dose, we genotyped 101 patients for the common UGT1A1-53(TA)(n) polymorphism and compared T(4) doses among patients having zero (5/6 and 6/6 genotypes), one (6/7 genotype), or two (7/7 and 7/8 genotypes) copies of the low-expression (TA) 7 and (TA) 8 alleles. A significant trend for decreasing T(4) dose with increasing number of copies of (TA)(7) and (TA)(8) (P = 0.037) and significant difference in T(4) dose across the UGT1A1-53(TA)(n) genotypes (P = 0.048) were observed, despite considerable overlap of T(4) doses among different genotypes. These results are consistent with reduced T(4) glucuronidation in patients with low-expression (TA) 7 and (TA) 8 alleles and provide the first evidence for association between UGT1A1-53(TA)(n) and T(4)-dose requirement for thyroid-stimulating hormone suppression in a natural clinical setting. Pharmacogenetics and Genomics 21: 341-343 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Pharmacogenetics and Genomics 2011, 21: 341-343

White-matter hyperintensities in first-episode psychosis

Background White-matter hyperintensities have been associated with both schizophrenia and mood disorders, particularly bipolar disorder, but results are inconsistent across studies. Aims To examine whether white-matter hyperintensities are a vulnerability marker for psychosis or are specifically associated with bipolar disorder. Method T-2-weighted magnetic resonance imaging data were acquired in 129 individuals with first-episode psychosis (either affective or non-affective psychoses) and 102 controls who were randomly selected from the same geographical areas. visual white-matter hyperintensity ratings were used for group and subgroup comparisons. Results There were no statistically significant between-group differences in white-matter hyperintensity frequency or severity scores. No significant correlations were found between white-matter hyperintensity scores and duration of illness, duration of untreated psychosis, or severity of psychotic, manic or depressive symptoms. Conclusions White-matter hyperintensities are not associated with vulnerability to psychosis in general, or specifically with affective psychoses. Further, first-episode psychosis investigations using more quantitative methods are warranted to confirm these findings. Declaration of interest None. Funding detailed in Acknowledgements.

Influence of the Fibroblast Growth Factor Receptor 4 Expression and the G388R Functional Polymorphism on Cushing`s Disease Outcome

Context: Abnormal FGFR4 expression has been detected in pituitary tumors, especially in larger and invasive adenomas. In addition, the FGFR4 functional polymorphism G388R has been associated with poor outcome in several human malignancies. Then, we hypothesized that FGFR4 expression and genotype could be markers of adverse outcome of Cushing`s disease after transsphenoidal surgery. Objectives: The objective was to investigate whether there is an association between the postoperative outcome of Cushing`s disease (remission/recurrence) and the FGFR4 G388R genotype or the FGFR4 expression in corticotrophinomas. Design and Patients: Clinical, hormonal, and pathological data of 76 patients who underwent the first transsphenoidal surgery were retrospectively reviewed. All patients were genotyped for G388R polymorphism. FGFR4 expression was assessed by real-time PCR in 18 corticotrophinomas. Main Outcome Measures: The outcome measures included the FGFR4 G388R genotype and FGFR4 expression in postoperative remission and recurrence of Cushing`s disease. Results: Homozygosis for FGFR4 glycine (Gly(388)) allele was associated with reduced disease-free survival, in the univariate analysis (hazard ratio of 6.91; 95% confidence interval of 1.14-11.26; P = 0.028). Male gender (P = 0.036), lack of pathology confirmation (P = 0.009), and cortisol levels more than 2 mu g/dl in the early postoperative period (P < 0.001) were also significant predictors of Cushing`s disease recurrence in the univariate analysis. FGFR4 overexpression was found in 44% of the corticotrophinomas, and it was associated with lower postoperative remission rate (P = 0.009). Conclusions: Our data suggest that homozygosis for FGFR4 Gly(388) allele and FGFR4 overexpression are associated with higher frequency of postoperative recurrence and persistence of Cushing`s disease, respectively. (J Clin Endocrinol Metab 95: E271-E279, 2010)