GABAB Receptor Agonist R-Baclofen Reverses Social Deficits and Reduces Repetitive Behavior in Two Mouse Models of Autism.

Autism spectrum disorder (ASD) is diagnosed by two core behavioral criteria, unusual reciprocal social interactions and communication, and stereotyped, repetitive behaviors with restricted interests. Excitatory/inhibitory imbalance is a prominent hypothesis for the etiology of autism. The selective GABAB receptor agonist R-baclofen previously reversed social deficits and reduced repetitive behaviors in a mouse model of Fragile X syndrome, and Arbaclofen improved some clinical symptoms in some Fragile X and ASD patients. To evaluate R-baclofen in a broader range of mouse models of ASD, we tested both the R-baclofen enantiomer and the less potent S-baclofen enantiomer in two inbred strains of mice that display low sociability and/or high repetitive or stereotyped behaviors. R-baclofen treatment reversed social approach deficits in BTBR T+ Itpr3tf/J (BTBR), reduced repetitive self-grooming and high marble burying scores in BTBR, and reduced stereotyped jumping in C58/J (C58), at nonsedating doses. S-baclofen produced minimal effects at the same doses. These findings encourage investigations of R-baclofen in other preclinical model systems. Additional clinical studies may be warranted to further evaluate the hypothesis that the GABAB receptor represents a promising pharmacological target for treating appropriately stratified subsets of individuals with ASD.

Is a routine ultrasound in the third trimester justified? Additional fetal anomalies diagnosed after two previous unremarkable ultrasound examinations.

PURPOSE: The detection of fetal structural abnormalities is a routine part of antenatal care. Ultrasound examination policies vary among European countries. An additional ultrasound for fetal structural anomalies in the 3 rd trimester seems important for many reasons. Some abnormalities develop or first become apparent later in pregnancy. The aim of the study was to analyze the rate of previously undetected structural abnormalities in the 3 rd trimester. MATERIALS AND METHODS: 8074 fetuses were examined in this prospective study between 1998 and 2008. All received an examination at 11 - 14 weeks and 79 % (6378 / 8074) of these fetuses also received an ultrasound at 20 - 24 weeks. If both of the examinations did not detect structural abnormalities, the fetuses were included in the study group and received an ultrasound at 28 - 32 weeks (n = 5044). New structural abnormalities in the 3 rd trimester were analyzed. The outcome was available in 96 % of the cases. RESULTS: The overall incidence of fetal malformations was 3.6 % (n = 289), of which 40 % (116 / 289) were diagnosed at 11 - 14 weeks. The following 2nd trimester scan revealed 102 (35 %) new fetal malformations. An additional 44 (15 %) structural abnormalities were found in the 3 rd trimester. These were mainly abnormalities of the urogenital system (n = 18). There were also anomalies of the cardiovascular system (n = 9), the gastrointestinal system (n = 6) and the central nervous system (n = 4). One of the cases had a previously undiagnosed abnormal karyotype. CONCLUSION: The ultrasound examination in the 3 rd trimester is of additional benefit and can detect previously unknown structural abnormalities. These findings are relevant for perinatal management and postnatal follow-up.

[Prenatal diagnosis of diastematomyelia and tethered cord - a case report and review of the literature]. / Pränataldiagnose einer Diastematomyelie und "tethered cord" - ein Fallbericht mit Literaturübersicht.

Diastematomyelia is a rare form of occult spinal dysraphism. It is characterized by longitudinal clefting and separating of the spinal cord by a bony or fibrous spur. Diastematomyelia is associated with other anomalies, i. e. spina bifida, scoliosis, visceral malformations or anomalies of the overlying skin. Prenatal diagnosis is based on fetal ultrasound supplemented by fetal MRI. We present a case of diastematomyelia and prenatal diagnosis in the 23rd gestational week using routine ultrasound scanning and confirmation by fetal MRI. After vaginal delivery at term, the child's development is normal. Prenatal diagnosis of isolated diastematomyelia is challenging. Management and prognosis are still controversial as only few cases have been reported. Affected fetuses might benefit from early diagnosis enabling surgical intervention before the development of neurological sequelae.

Urban cause-specific socioeconomic mortality differences. Which causes of death contribute most?

BACKGROUND: Cause-specific information on socioeconomic differences in health is necessary for a rational public health policy. At the local level, the Municipal Health Service studies these differences in order to support the authorities in policy making. METHODS: Mortality data of the under 65 age group in The Hague were analysed (1982-1991) at residential area level. RESULTS: Causes of death with a high socioeconomic gradient among males were: homicide, chronic liver disease, 'other' external causes of injury, diabetes, bronchitis, emphysema and asthma, and motor vehicle accidents; and among females: diabetes, ischaemic heart disease, 'other' diseases of the circulatory system, signs, symptoms and ill-defined conditions, malignant neoplasm of cervix, and 'other' diseases. Main contributors to the mortality differences between the highest and lowest socioeconomic quartiles among males were: ischaemic heart disease (17.3%), 'other' diseases of the circulatory system (10.2%), signs, symptoms and ill-defined conditions (9.0%), 'other' external causes of injury (8.6%), and chronic liver disease (7.2%); and among females: ischaemic heart disease (25.5%), 'other' diseases (20.1%), signs, symptoms and ill-defined conditions (18.6%), 'other' diseases of the circulatory system (11.0%), and diabetes (9.1%). Among females the contributions of malignant neoplasms of breast (-16.3%) and colon (-5.5%) and suicide (-4.3%) were negative. CONCLUSIONS: The diseases that are the main contributors to urban socioeconomic mortality differences can be influenced by public health policy.

Diabetes mellitus among South Asian inhabitants of the Hague: high prevalence and an age-specific socioeconomic gradient

BACKGROUND: The prevalence of diabetes mellitus is known to be high among South Asians. The Municipal Health Service in The Hague investigated the prevalence of self-reported diabetes among South Asian inhabitants of The Hague, and the relationship between diabetes prevalence and socioeconomic status in this population. METHODS: A total of 3, 131 South Asians >30 years of age, randomly selected (stratified according to age and sex), were included in a postal survey with subsequent telephone interviews with non-respondents. RESULTS: Self-reported diabetes prevalence varies from 6.4 percent in the 31-49 year group to 37.1 percent in the over 60s age group. The relationship with age varies across the different socioeconomic strata. There are only a few people with diabetes in the 31-39 year age group in the highest stratum, whereas in the lowest stratum at the same age the prevalence of self-reported diabetes approximates 20 percent. In the over 60s age group the prevalence of diabetes does not significantly differ between the higher and lower socioeconomic strata. CONCLUSIONS: Diabetes is an extremely common disease among South Asian inhabitants of The Hague. In this population, the relationship between diabetes prevalence and socioeconomic status varies with age. Cohort and age effects may account for this varaiation. (AU)

[Epidemiology of attempted suicide in The Hague]. / Epidemiologie van parasuïcide in Den Haag.

OBJECTIVE: To estimate the incidence of parasuicide in a metropolitan area and to identify subgroups of individuals with the purpose of developing secondary preventive strategies. DESIGN: Longitudinal prospective case register study (1987-1993). METHOD: In the city of the Hague, the Netherlands, all individual contacts concerning parasuicidal behaviour were registered by the participating facilities i.e., hospitals, community mental health organizations and emergency services. Demographic and case-related information was recorded. Record linkage of the anonymized data including those of the municipal coroner concerning suicide was done by the project administration for longitudinal monitoring. RESULTS: Over the registration period of 7 years (1987-1993) 4458 parasuicidal acts were recorded involving 3333 individuals. The age and sex distribution was in accordance with formerly published national and local data, but the real numbers of parasuicide rates were 50-100% higher than those usually presented in the literature. Repetition of parasuicide during an average follow-up period of 3.8 years occurred in 18.2% of all cases and the repetition rate increased over time. The suicide risk within a year after the last registered parasuicide came to 1.5% for men as well as women, and that within four years to 1.9% for women and 2.9% for men. Men and women with a history of three or more acts of parasuicide had a suicide risk of over 5% in a follow-up period of 4 years. The incidence of parasuicide was highest in the younger age groups of non-European women (including Turkish women), in particular those with an ethnocultural background in Surinam.

Diabetes mellitus among South Asian inhabitants of The Hague: high prevalence and an age-specific socioeconomic gradient.

BACKGROUND: The prevalence of diabetes mellitus is known to be high among South Asians. The Municipal Health Service in The Hague investigated the prevalence of self-reported diabetes among South Asian inhabitants of The Hague, and the relationship between diabetes prevalence and socioeconomic status in this population. METHODS: A total of 3,131 South Asians >30 years of age, randomly selected (stratified according to age and sex) from the municipal register, were included in a postal survey with subsequent telephone interviews with non-respondents. RESULTS: Self-reported diabetes prevalence varies from 6.4% in the 31-49 year age group to 37.1% in the over 60s age group. The relationship with age varies across the different socioeconomic strata. There are only a few people with diabetes in the 31-39 year age group in the highest stratum, whereas in the lowest stratum at the same age the prevalence of self-reported diabetes approximates 20%. In the over 60s age group the prevalence of diabetes does not significantly differ between the higher and lower socioeconomic strata. CONCLUSIONS: Diabetes is an extremely common disease among South Asian inhabitants of The Hague. In this population, the relationship between diabetes prevalence and socioeconomic status varies with age. Cohort and age effects may account for this variation.