Tyrosine hydroxylase deficiency: a treatable disorder of brain catecholamine biosynthesis

Tyrosine hydroxylase deficiency is an autosomal recessive disorder resulting from cerebral catecholamine deficiency. Tyrosine hydroxylase deficiency has been reported in fewer than 40 patients worldwide. To recapitulate all available evidence on clinical phenotypes and rational diagnostic and therapeutic approaches for this devastating, but treatable, neurometabolic disorder, we studied 36 patients with tyrosine hydroxylase deficiency and reviewed the literature. Based on the presenting neurological features, tyrosine hydroxylase deficiency can be divided in two phenotypes: an infantile onset, progressive, hypokinetic-rigid syndrome with dystonia (type A), and a complex encephalopathy with neonatal onset (type B). Decreased cerebrospinal fluid concentrations of homovanillic acid and 3-methoxy-4-hydroxyphenylethylene glycol, with normal 5-hydroxyindoleacetic acid cerebrospinal fluid concentrations, are the biochemical hallmark of tyrosine hydroxylase deficiency. The homovanillic acid concentrations and homovanillic acid/5-hydroxyindoleacetic acid ratio in cerebrospinal fluid correlate with the severity of the phenotype. Tyrosine hydroxylase deficiency is almost exclusively caused by missense mutations in the TH gene and its promoter region, suggesting that mutations with more deleterious effects on the protein are incompatible with life. Genotype-phenotype correlations do not exist for the common c.698G > A and c.707T > C mutations. Carriership of at least one promotor mutation, however, apparently predicts type A tyrosine hydroxylase deficiency. Most patients with tyrosine hydroxylase deficiency can be successfully treated with l-dopa.

Prevalence of Alcohol-Related Problems in an Elderly Population and Their Association With Cognitive Impairment and Dementia

Background: Studies investigating the association between alcohol use and cognitive disorders in the elderly population have produced divergent results. Moreover, the role of alcohol in cognitive dysfunction is not clear. The aims of this study were to estimate the prevalence of alcohol-related problems in an elderly population from Brazil and to investigate their association with cognitive and functional impairment (CFI) and dementia. Methods: A community-based cross-sectional study was performed. A sample of 1,145 elderly people was examined in 2 phases. Several instruments were utilized in the first phase: the CAGE questionnaire was used to identify potential cases of alcohol-related problems, and a screening test for dementia was used to estimate CFI. The CAMDEX interview (Cambridge Examination) and DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) criteria were used for the clinical diagnosis of dementia in the second phase. Results: ""Heavy alcohol use"" (CAGE >= 2) was found in 92 subjects (prevalence: 8.2%). It was associated with gender (males, p < 0.001), low education (only in females, p = 0.002), and low socioeconomic level (p = 0.001, in females; p = 0.002, in males). The Mini Mental State Examination exhibited a nonlinear relationship with alcohol-related problems in females; ""mild-moderate alcohol use"" (CAGE < 2) presented the highest score. A significant association between alcohol-related problems and cognitive dysfunction was found only in females. ""Heavy alcohol use"" was associated with higher CFI and dementia rates compared to ""mild-moderate alcohol use"" (p = 0.003 and p < 0.001, respectively). ""Mild-moderate alcohol use"" had a tendency of association with lower CFI and dementia rates when compared to ""no alcohol use"" (p = 0.063 and 0.050, respectively). Conclusion: Our findings suggest that alcohol use does not have a linear relationship with cognitive decline.

Trade spectrum of K4-e

A K-4 - e trade consists of two disjoint decompositions of some simple graph H into copies of K-4 - e. The number of vertices of H is referred to as the foundation of the trade, while the number of copies of K-4 - e in each of the decompositions is called the volume of the trade. We determine the values of v and s for which there exists a K-4 - e trade of volume s and foundation v.

Effects of maternal glycemia on fetal heart rate in pregnancies complicated by pregestational diabetes mellitus

Objective: To investigate the influence of maternal glycemia on fetal heart rate (FHR) parameters analyzed by computerized cardiotocography in fetuses of diabetic mothers in the third trimester. Study design: Thirty-nine pregnant women with pregestational diabetes mellitus were studied prospectively. The inclusion criteria were a diagnosis of pregestational diabetes, singleton pregnancy between 36 and 40 weeks, and absence of fetal abnormalities. Computerized cardiotocography (System 8002) was performed over a period of 60 min and capillary glycemia was measured immediately before and 30 and 60 min after the beginning of the exam. The evaluations were done 2 h after lunch. Results: Nineteen patients (48.7%) presented mean glycemia >= 120 mg/dL The mean basal FHR was 136.7 +/- 10.0 bpm in the group with glycemia <120 mg/dL and 144.8 +/- 9.4 bpm in the group with glycemia >= 120 mg/dL (p = 0.013, Student`s t test). There was a significant positive correlation (Pearson`s test, p = 0.0001, r = 0.57) between basal FHR and mean glycemia. A significant negative correlation was observed between short-term variation and mean glycemia (Pearson`s test, p = 0.003, r = -0.47). No significant differences were observed between the other indices evaluated by computerized cardiotocography and glycemia. Conclusions: Maternal hyperglycemia at the time of cardiotocography is associated with elevated FHR. It seems to be important to understand how FHR parameters are influenced by maternal glycemic status at the time of fetal assessment in pregnancies complicated by diabetes. (C) 2009 Published by Elsevier Ireland Ltd.

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.

Morphometric Study on the Anatomy of the Fetal Cricoid Cartilage and Comparison Between Its Inner Diameter and Endotracheal Tube Sizes

Objectives: The high incidence of respiratory disorders is one of the main problems in perinatal medical care. With the increased use of intubation, the incidence of laryngeal injury causing stenosis has also increased. The principal constriction point in the infant`s larynx is the midcricoid area. We sought to provide detailed morphometric data on the anatomy of the cricoid cartilage and its relationship with growth and body characteristics of fetuses at 5 to 9 months of gestational age. Methods: Nineteen larynges obtained from 17 stillborn infants and 2 newborn infants ranging in gestational age from 5 to 9 months were studied. Measurements of the cricoid cartilage were made with a millimeter-graded caliper. Results: Weight was the variable most correlated with cricoid measurements. The cricoid lumen configuration showed an almost elliptic shape and did not change with gestational age. The mean inner subglottic cricoid area was 19.27 +/- 9.62 mm(2) and was related to weight and body surface area. Cricoid growth was more pronounced at the outer portion of the cartilage. Conclusions: The cricoid lumen configuration was elliptic, and its mean area was smaller than that of available endotracheal tubes. This lumen area was most influenced by weight and height.

Effectiveness of the CAGE questionnaire, gamma-glutamyltransferase and mean corpuscular volume of red blood cells as markers for alcohol-related problems in the workplace

Objective: To evaluate the usefulness of gamma-glutamyltransferase (GGT) and mean corpuscular volume (MCV), as well as that of the CAGE questionnaire, in workplace screening for alcohol abuse/dependence. Methods: A total of 183 male employees were submitted to structured interviews (Structured Clinical Interview for DSM-IV 2.0 and CAGE questionnaire). Blood samples were collected. Diagnostic accuracy and odds ratio were determined for the CAGE, GGT and MCV. Results: The CAGE questionnaire presented the best sensitivity for alcohol dependence (91%; specificity, 87.8%) and for alcohol abuse (87.5%, specificity, 80.9%), which increased when the questionnaire was used in combination with GGT (sensitivity, 100% and 87.5%, respectively; specificity, 68% and 61.5, respectively). CAGE positive results and/or alterations in GGT were less likely to occur among employees not presenting alcohol abuse/ dependence than among those presenting such abuse (OR for CAGE = 13, p < 0.05; OR for CAGE-GGT = 11, p < 0.05) or dependence (OR for CAGE = 76, p < 0.0 1; OR for GGT = 5, p < 0.0 1). Employees not presenting alcohol abuse/dependence were also several times more likely to present negative CAGE or GGT results. Conclusions: The use short, simple questionnaires, combined with that of low-cost biochemical markers, such as GGT, can serve as an initial screening for alcohol-related problems, especially for employees in hazardous occupations. The data provided can serve to corroborate clinical findings. (C) 2008 Elsevier Ltd. All rights reserved.

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.

The Role of SRY Mutations in the Etiology of Gonadal Dysgenesis in Patients with 45,X/46,XY Disorder of Sex Development and Variants

Background: The potential involvement of SRY in abnormal gonadal development in 45,X/46,X,der(Y) patients was proposed following the identification of SRY mutations in a few patients with Turner syndrome (TS). However, its exact etiological role in gonadal dysgenesis in patients with Y chromosome mosaicisms has not yet been clarified. Aims: It was the aim of this study to screen for allelic variation in SRY in a large cohort of patients with disorders of sex development due to chromosomal abnormalities with 45, X/46, X, der(Y) karyotype. Patients: Twenty-seven patients, 14 with TS and 13 with mixed gonadal dysgenesis (MGD), harboring 45, X/46, X, der(Y) karyotypes were selected. Methods: Genomic DNA was extracted from peripheral blood leukocytes of all patients and from gonadal tissue in 4 cases. The SRY coding region was PCR amplified and sequenced. Results: We identified only 1 polymorphism (c.561C -> T) in a 45,X/46,XY MGD patient, which was detected in blood and in gonadal tissue. Conclusion: Our results indicate that mutations in SRY are rare findings in patients with Y chromosome mosaicisms. Therefore, a significant role of mutated SRY in the etiology of gonadal dysgenesis in patients harboring 45, X/46, XY karyotype and variants seems very unlikely. Copyright (C) 2010 S. Karger AG, Basel

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.