Genetic susceptibility to tardive dyskinesia in chronic schizophrenia subjects: III. Lack of association of CYP3A4 and CYP2D6 gene polymorphisms

Recent studies of the association between the metabotropic glutamate receptor 3 gene (GRM3) and schizophrenia have produced conflicting results, although GRM3 is a promising candidate gene. Fujii et al. found a single nuclear polymorphism (SNP) for within this gene, rs1468412 to have a positive association to schizophrenia in Japanese patients. To investigate this further, we genotyped 7 SNPs around GRM3 including rs1468412, in 752 Chinese patients with schizophrenia and 752 controls using Taqman technology. We did not detect any association between rs1468412 and schizophrenia, however we found differences in the allele frequency distribution of SNP rs2299225 (p=0.0297, odds ration [OR]=1.44, 95% confidence interval 1.05-1.99) between cases and controls. Moreover, the overall frequency of haplotypes constructed from three SNPs including rs2299225 showed significant differences between cases and controls (p=0.0017). Our results partially support the previous studies in other ethnic groups and indicate that the GRM3 gene may play an important role in the etiology of schizophrenia in the Han Chinese.     

Aspiration cytology of sarcomatoid carcinoma of the breast: Report of a case with cystic change

Sarcomatoid/metaplastic carcinomas of the breast are rare breast malignancies that show a myriad of cytohistologic patterns in aspirates. These poorly differentiated invasive carcinomas contain both ductal and mesenchymal elements with transitional forms displaying either spindle, squamous, chondroid, or osseous differentiation. We describe such a neoplasm in a 68-yr-old woman, the diagnosis of which was missed at the initial fine-needle aspiration (FNA) due to cystic change. Extensive cystic change in a sarcomatoid carcinoma is unusual and is reported for the first time in the English literature.     

Childhood brucellosis--a microbiological, epidemiological and clinical study

A total of 5726 blood specimens (from children aged 14 years and younger) were studied for the serological evidence of brucellosis. Ninety-three (1.6 per cent) showed diagnostic agglutinin titres with a geometric mean titre of 403 (SD +/- 547). Forty-three (59.7 per cent) blood specimens yielded the growth of Brucella melitensis. Thirty-nine patients (41.93 per cent) were shepherds, who constituted the major occupational group affected in the present series. More than 60 per cent of the patients had a history of both consumption of fresh goat's milk and close animal contact. The habit of consuming fresh goat's milk to obtain relief from chronic ailments was noted in nine patients. Seventy-three (78.49 per cent) were males and 20 (21.51 per cent) were females, with a male to female ratio of 3:1. The disease occurred mainly in the school age group (mean age 10.3 years). All the patients had an acute history of less than 2 months. Forty-nine (52.68 per cent) patients presented with persistent fever, 19 (20.43 per cent) with joint pain, and the rest with a combination of fever and joint pain with and without low backache, fever being the commonest complaint. One case presented with involuntary movements of limbs alone and the other with burning feet only. Pityriasis alba was the consistent physical finding, with fever in the majority of the patients. The major joint found to be involved was the knee (52.77 per cent). The synovial fluid obtained from the knee joint of five patients demonstrated Brucella agglutinins and also three grew B. melitensis. Eight patients presented with complications that included skin lesions (3), carditis (2), neurobrucellosis such as chorea (1), peripheral neuritis (1), and meningitis (1). Brucella melitensis biotype 1 was successfully isolated from the papular eruption of one out of three cases who presented with skin lesions. To our knowledge this is the fourth confirmed isolation of B. melitensis from skin lesions with brucellosis, reported in the literature. The cerebrospinal fluid obtained from the meningitis patient was positive for B. agglutinins. To our knowledge chorea of brucellar origin appears to be the first case reported in the literature. In 15 cases (16.13 per cent) brucellosis was suspected clinically whereas 78 (83.87 per cent) cases, only serological evidence of brucellosis confirmed the diagnosis. None of the cases relapsed. In our experience an initial combination therapy with a three-drug regimen followed by a two-drug regimen for a minimum of 6 weeks has been found to be effective in the prevention of a relapse.     

Improving asthma outcomes in harder-to-reach populations: challenges for clinical and community interventions

The burden of asthma differs from country to country and within populations. The factors that influence this variation include asthma prevalence and severity, aspects of healthcare services (such as accessibility, quality and utilisation) and social demographic factors (such as income inequality, cultural and linguistic diversity and indigenous populations). The identification of individuals and populations that are 'harder to reach', 'special' or at greater risk of poor asthma outcomes therefore depends on how the burden of asthma and its management are measured. Meeting the challenge of educating harder-to-reach populations with asthma is the focus of this article. In clinical settings, communication is the mainstay of engaging and building trust to influence behavioural change in individuals; community-based interventions provide valuable opportunities for targeting harder-to-reach populations. However, they require active community consultation and participation and innovative approaches to service delivery, in addition to being theoretically driven and systematically developed.     

11beta-alkyl-Delta9-19-nortestosterone derivatives: high-affinity ligands and potent partial agonists of the androgen receptor

We report the synthesis of novel steroidal androgen receptor ligands comprising 11beta-alkyl-Delta(9)-derivatives of 19-nortestosterone. These compounds are structurally related to the antiprogestin, antiglucocorticoid, and antiandrogen drug mifepristone (RU486). Nortestosterone analogues bearing 11beta-octyl and 11beta-decyl side-chains bind tightly to recombinant AR protein (IC(50) = 6.6 nM and IC(50) = 0.8 nM), block AR dimerization, exhibit activity against LNCaP prostate cancer cells, and comprise partial AR agonists with low antiglucocorticoid activity.     

Evaluation of familial influences on the course and severity of schizophrenia among US and Indian cases

Abstract.Background: Prior studies suggest familial (possibly genetic) influences on the course of schizophrenia.Aims: The aim of this study was to compare familial influences on the course and severity of schizophrenia in two independent samples.Method: Thirteen selected measures were compared among affected sibling pairs (ASPs) from Pittsburgh, USA and New Delhi, India (48 US pairs, 53 Indian pairs). For each ASP proband, an unrelated patient was selected randomly from a suitable pool of cases ascertained in the same study (Sibpair proband—comparison case or S-C pairs). Correlations between these pairs were compared.Results: The correlations varied by item and by site. Significant correlations for longitudinal course and pattern of severity were noted among the ASPs from USA, but did not remain significant following corrections for multiple comparisons. Comparisons between the correlations for ASPs and the S-C pairs, used to estimate familial effects, yielded trends for the ASP correlations to be numerically larger than the S-C correlations in both samples. Separate cross-site comparisons revealed several significant differences with regard to several demographic and clinical variables. The possible impact of the cross-site variations on the observed ASP correlations is discussed.Conclusions: Though familial factors did not appear to have a significant impact on course/severity using this novel design, the suggestive trends need to be examined in larger samples.     

Dynamics of CD4 and CD8 T cell responses to cytomegalovirus in healthy human donors

To study the dynamics of cytomegalovirus (CMV) immunity in healthy immunocompetent hosts, interferon-gamma-producing CD4 and CD8 T cell responses in the presence or absence of CMV antigens were measured from 15 CMV-seropositive donors and 13 CMV-seronegative donors. Cytokine responses in the absence of antigen were significantly higher in CMV-seropositive donors. Also, a disproportionate number of CD69(+) cells isolated ex vivo from CMV-seropositive donors were specific for CMV, suggesting recent reactivation in vivo. To examine changes in cellular responses over time, 10 seropositive donors were tested over a 6-month period. About half of the donors showed significant variability over time, but staphylococcal enterotoxin B responses remained relatively constant. These findings suggest that CMV can present a considerable and recurrent burden to the human immune system. By understanding the normal dynamics of CMV responses over time, it may be possible to better identify aberrant responses to CMV in immunocompromised hosts.