Neuropeptide levels in the basal ganglia of aged common marmosets following prolonged treatment with MPTP

Summary Aged common marmosets were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 0.5–2.0 mg/kg/week i.p.) for 16 or 24 weeks, observed for a total of 30 weeks and then killed for measurement of biochemical pramaters in basal ganglia. The MPTP treatment induced a marked depletion in dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels in the caudate nucleus and putamen. In contrast, the concentrations of five neuropeptides: [Met⁵]-enkephalin, [Leu⁵]-enkephalin, cholecystokinin, substance P and neurotensin as measured by a combined HPLC/RIA method, remained unaltered in all basal ganglia regions examined. Enkephalin precursor levels, as reflected by cryptic [Met⁵]-enkephalin content, were increased in the putamen, but not in the caudate nucleus, as a consequence of MPTP administration. Cryptic [Leu⁵]-enkephalin content remained unchanged in the striatum of MPTP treated marmosets. Overall, these results suggest an increase in striatal [Met⁵]-enkephalin release following chronic MPTP treatment of aged marmosets. However, the chronic treatment of aged marmosets with MPTP does not reproduce the neuropeptide alterations characteristic of Parkinson's disease.     

Cross-cultural invariance of the Academic Expectations Stress Inventory: Adolescent samples from Canada and Singapore

We provide further evidence for the two-factor structure of the 9-item Academic Expectations Stress Inventory (AESI) using confirmatory factor analysis on a sample of 289 Canadian adolescents and 310 Singaporean adolescents. Examination of measurement invariance tests the assumption that the model underlying a set of scores is directly comparable across groups. This study also examined the cross-cultural validity of the AESI using multigroup confirmatory factor analysis across both the Canadian and Singaporean adolescent samples. The results suggested cross-cultural invariance of form, factor loadings, and factor variances and covariances of the AESI across both samples. Evidence of AESI's convergent and discriminant validity was also reported. Findings from t-tests revealed that Singaporean adolescents reported a significantly higher level of academic stress arising from self expectations, other expectations, and overall academic stress, compared to Canadian adolescents. Also, a larger cross-cultural effect was associated with academic stress arising from other expectations compared with academic stress arising from self expectations.     

Working‐correlation‐structure identification in generalized estimating equations

Selecting an appropriate working correlation structure is pertinent to clustered data analysis using generalized estimating equations (GEE) because an inappropriate choice will lead to inefficient parameter estimation. We investigate the well‐known criterion of QIC for selecting a working correlation structure, and have found that performance of the QIC is deteriorated by a term that is theoretically independent of the correlation structures but has to be estimated with an error. This leads us to propose a correlation information criterion (CIC) that substantially improves the QIC performance. Extensive simulation studies indicate that the CIC has remarkable improvement in selecting the correct correlation structures. We also illustrate our findings using a data set from the Madras Longitudinal Schizophrenia Study. Copyright © 2008 John Wiley & Sons, Ltd.     

Imaging findings of the developing temporal bone in fetal specimens.

PURPOSETo trace the development of the normal fetal temporal bone by means of plain radiography, MR, and CT.METHODSEighteen formalin-fixed fetal specimens, 13.5 to 24.4 weeks'' gestational age, were examined with a mammographic plain film technique, CT, and MR imaging at 1.5 T. Temporal bone development and ossification were assessed.RESULTSThe membranous labyrinth grows with amazing rapidity and attains adult size by the middle of the gestation period. The cochlea, vestibule, and semicircular canals are very prominent and easily recognized on MR images. The otic capsule develops from a cartilage model. Ossification of the otic capsule proceeds rapidly between 18 and 24 weeks from multiple ossification centers that replace the cartilaginous framework. The mastoid, internal auditory canal, vestibular aqueduct, and external auditory canal continue to grow after birth.CONCLUSIONThe study of fetal developmental anatomy may lead to a better understanding of congenital disorders of the ear. Faster MR scanning techniques may provide a method for in utero evaluation of the fetal temporal bone.     

Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia.

BACKGROUND: Hypofunction of N-methyl-D-aspartate glutamate receptor had been implicated in the pathophysiology of schizophrenia. Treatment with D-serine or glycine, endogenous full agonists of the glycine site of N-methyl-D-aspartate receptor, or D-cycloserine, a partial agonist, improve the symptoms of schizophrenia. N-methylglycine (sarcosine) is an endogenous antagonist of glycine transporter-1, which potentiates glycine's action on N-methyl-D-aspartate glycine site and can have beneficial effects on schizophrenia. METHODS: Thirty-eight schizophrenic patients were enrolled in a 6-week double-blind, placebo-controlled trial of sarcosine (2 g/d), which was added to their stable antipsychotic regimens. Twenty of them received risperidone. Measures of clinical efficacy and side effects were determined every other week. RESULTS: Patient who received sarcosine treatment revealed significant improvements in their positive, negative, cognitive, and general psychiatric symptoms. Similar therapeutic effects were observed when only risperidone-treated patients were analyzed. Sarcosine was well-tolerated, and no significant side effect was noted. CONCLUSIONS: Sarcosine treatment can benefit schizophrenic patients treated by antipsychotics including risperidone. The significant improvement with the sarcosine further supports the hypothesis of N-methyl-D-aspartate receptor hypofunction in schizophrenia. Glycine transporter-1 is a novel target for the pharmacotherapy to enhance N-methyl-D-aspartate function.     

Localized cerebral proton MR spectroscopy in HIV infection and AIDS.

PURPOSETo document differences in the cerebral proton MR spectra of patients with early and late stages of human immunodeficiency virus (HIV) infection.METHODWe studied the relative N-acetyl-aspartate (NAA) levels by localized proton spectroscopy of the parietooccipital region of the brain in 43 HIV-seropositive patients, including 26 with an acquired immunodeficiency syndrome (AIDS)-defining diagnosis, and in eight control subjects.RESULTSReduced relative NAA levels were shown in those HIV-1-seropositive patients: 1) with AIDS against HIV-1-seropositive patients without AIDS (P < .04); 2) with HIV-1-associated cognitive/motor complex against neurologically healthy patients (P < .007); 3) with encephalopathic changes on MR against those with normal imaging (P < .001); and 4) on follow-up against their results on initial study (P < .03).CONCLUSIONSBy clinical (Centers for Disease Control classification) and radiologic (MR evidence of white-matter disease) criteria indicating late-stage HIV infection, reduced relative levels of NAA have been demonstrated. Spectroscopic abnormalities can be quantitatively tracked with time. This paper demonstrates the clinical use of detecting NAA as a putative in vivo measure of the neuronal loss that has been demonstrated in postmortem studies of patients with AIDS. This neuronal loss, which is believed to underlie the HIV-1-associated cognitive/motor complex, is thought to be attributable directly or indirectly to the presence of HIV in the brain. Proton spectroscopy may serve as a quantitative noninvasive indicator of this aspect of cerebral involvement in HIV disease.     

The epidemiology of urinary dysfunction in Chinese women

The epidemiology of urinary dysfunction in a Chinese population living in Hong Kong was investigated. Fifteen hundred ethnic Chinese women answered a telephone questionnaire including symptoms of urinary dysfunction, anthropometric measurements, obstetric history and place of birth. The relative predictive value of these factors was analyzed using logistic regression. The prevalence of urinary dysfunction was 13%. Ten percent reported stress incontinence, and 4% had urgency or urge incontinence. The strongest predictor was place of birth, with women born in mainland China having the highest prevalence of pure stress incontinence (OR 1.33, CI 1.1–1.6). For the symptoms of detrusor instability age was the strongest predictor, with women over 50 years being at greater risk (OR 2.8, CI 1.6–5.0). Contrary to earlier beliefs, urinary dysfunction in Chinese women is as common as in Caucasian women. Place of birth is the strongest predictor for pure stress incontinence, with women born in mainland China being at greater risk. This suggests that environmental factors in early life have a differential effect on the development of urinary incontinence. EDITORIAL COMMENT: Taiwan Chinese women have a comparable prevalence of urinary dysfunction with Hong Kong Chinese women. A survey representing a multistage sample of 82 678 women aged 18 years or older was conducted in the Taipei area from January to June 1993. A total of 818 cases were interviewed by trained students. One hundred and eighty-nine (23.1%) of the respondents reported having had some degree of incontinence in the preceding 12 months, 28 (3.4%) reporting regular incontinence. Most presented with stress urinary incontinence, whereas urge incontinence and mixed incontinence were more commonly seen in the elderly group (aged 60 years or older). The risk factors for urinary incontinence included age, number of vaginal deliveries (>3), number of abortions (>2) and maternal history of incontinence. Voiding symptoms (irritative or obstructive) and constipation were significantly more prevalent among respondents with incontinence than those without (P<0.001). This evidence also indicates that the long-held belief that Chinese women have a much lower prevalence of urinary dysfunction than western women has all but ended.