High dose antipsychotic use in schizophrenia: findings of the REAP (research on east Asia psychotropic prescriptions) study.

BACKGROUND: High-dose antipsychotic regimes (defined as the prescription of more than 1000 chlorpromazine-equivalents milligrams of antipsychotic per day) in the management of patients with schizophrenia are not uncommon, but most reports are from western countries. Recent functional neuroimaging studies have found that the previous notion concerning the use of antipsychotic medication, especially in high doses, was unsupported and untenable. METHODS: This international study examined the use of high dose antipsychotic medication and its clinical correlates in schizophrenia patients within six East Asian countries/territories. RESULTS: Within the study group (n = 2399), 430 patients (17.9%) were prescribed high dose antipsychotics. Antipsychotic use varied significantly between countries, with Japan, Korea, and Singapore using higher doses than the other countries. High dose antipsychotic use was associated with younger age in Japan (p < 0.001), longer duration of admission (p < 0.001), duration of illness (p < 0.001, particularly in Korea and Taiwan), positive psychotic symptoms (p < 0.001, particularly in Japan and Korea), and aggression (p < 0.05, particularly in Japan), and also with a higher likelihood of extrapyramidal and autonomic adverse effects (p < 0.05, particularly in China). Country, younger age, the presence of delusions and disorganized speech, polypharmacy, and receiving depot medication but not atypical antipsychotic drugs were important predictors of high antipsychotic use. CONCLUSIONS: This survey revealed that high antipsychotic dosing is not an uncommon practice in East Asia. It behooves the prescribing clinicians to constantly reevaluate the rationale for such a practice.

The contribution of D-mannose, L-fucose, N-acetylglucosamine, and selectin residues on the binding of glycodelin isoforms to human spermatozoa.

Previous data showed that glycodelin-A from amniotic fluid and glycodelin-F from follicular fluid inhibited sperm-zona pellucida binding. Solubilized zona pellucida reduced the binding of glycodelin-F to sperm extract dose dependently. This study demonstrated that the zona pellucida proteins also reduced the binding of glycodelin-A to sperm extract. Ionophore-induced acrosome reaction reduced the binding of iodinated glycodelin-A and -F to sperm, indicating that the glycodelin-binding sites are on the outer acrosomal membrane or on the sperm plasma membrane overlying the acrosome. While the binding of glycodelin-A to sperm was suppressed by mannose and fucose neoglycoproteins, that of glycodelin-F was also reduced by acetylglucosamine neoglycoprotein. Pretreatment of sperm with inhibitors of mannosidase and acetylglucosaminidase reduced the binding of glycodelin-F to sperm. On the other hand, inhibitor of mannosidase but not of acetylglucosaminidase inhibited the binding of glycodelin-A. In a competition binding assay, mannosidase reduced both glycodelin-A and -F binding whereas acetylglucosaminidase reduced only glycodelin-F binding. While fucosidase reduced the binding of both glycodelins, fucosidase inhibitor was marginally active in suppressing the binding of glycodelins to human sperm. Among the selectins tested, only E-selectin had a slight inhibitory effect on the binding of glycodelin-A to sperm. The binding of glycodelin-F was unaffected by selectins and their antibodies. In conclusion, the binding of glycodelin-A to sperm involves mannose, fucose, and possibly E- selectin residues, while that of glycodelin-F involves mannose, fucose, and N-acetylglucosamine but not the selectin residue.

Immunologic profile of patients with protein-losing enteropathy complicating congenital heart disease.

The immunologic profile of patients with congenital heart disease complicated by protein-losing enteropathy (PLE) is undefined. The aim of this study was to assess the lymphocyte subpopulation and immunglobulin (Ig) pattern in patients with PLE complicating congenital heart disease. The immunologic profile of six patients with congenital heart disease complicated by PLE was compared to that of controls without PLE matched for age and cardiac interventions. Enteric protein loss was documented by Tc99m-labeled albumin scintigraphy. The lymphocyte subpopulations were enumerated using flow cytometry, whereas serum IgG, IgA, and IgM concentrations were measured by the turbidimetric technique. The cardiac diagnoses included complex cyanotic heart disease post-Fontan procedure (n = 3), and one each of tetralogy of Fallot, restrictive cardiomyopathy, and valvar pulmonary stenosis. In patients with PLE, the T lymphocyte (CD3+) count was significantly lower (300 +/- 186 vs 2070 +/- 1171/microl, p = 0.017); both the helper/inducer lymphocytes (CD4+) (127 +/- 158 vs 927+/- 377/microl, p = 0.006) and suppressor/cytotoxic lymphocytes (CD8+) (129 +/- 49 vs 850 +/- 695/microl, p = 0.057) reduced with reversal of CD4(+)/CD8(+) ratio (0.81 +/- 0.68 1.64 +/- 0.89, p = 0.027). Furthermore, IgG level was significantly reduced (5.12 +/- 2.84 vs 12.5 +/- 1.58 g/L, p = 0.005) and IgA level tended to be lower (1.36 +/- 1.37 vs 2.50 +/- 0.80 g/L, p = 0.095). In contrast, the B lymphocyte (CD19+) count (340 +/- 151 vs 618 +/- 427/microl, p = 0.25), natural killer cell count (CD16(+) 56(+) CD3(-)) (252 +/- 212 vs 276 +/- 251/microl, p = 0.85), and IgM level (0.98 +/- 0.59 vs 1.12 +/- 0.25 g/L, p = 0.67) were similar for both groups. None of the patients developed opportunistic or severe viral infections. Abnormal immunologic profile of both the cellular and humoral arms of the immune system occurs in patients with congenital heart disease complicated by PLE. Nonetheless, these abnormalities perhaps appear quantitative rather than qualitative in nature, although further functional studies of antibody production and lymphocyte proliferation assays are required to support this proposition.

Expression of protein kinase C isoforms in euxanthone-induced differentiation of neuroblastoma cells.

Euxanthone, a potent neuritogenic compound isolated from the roots of the medicinal herb Polygala caudata, has recently been shown to induce the differentiation of murine neuroblastoma Neuro 2A (BU-1) cells. In this study, the role of protein kinase C (PKC) and the expression of various PKC isoforms in euxanthone-treated BU-1 cells were examined. mRNA phenotyping using the reverse-transcription polymerase chain reaction (RT-PCR) showed that BU-1 cells express six different PKC isoforms, namely PKC-alpha, -beta, -delta, -epsilon, -lambda, and -zeta. Differential regulation and expression of PKC isoforms was observed in BU-1 cells treated with 100 microM euxanthone. PKC-apha, -beta, -delta, -lambda and -zeta were all up-regulated, with 1.7- to 9.5-fold increase, at around 30 to 60 minutes after euxanthone treatment. The expression level of PKC-epsilon remained relatively constant during the treatment. PKC-gamma, -eta, and -theta were not detected in both untreated and euxanthone-treated BU-1 cells. Staurosporine, a broad spectrum PKC inhibitor, was found to inhibit both spontaneous and euxanthone-induced neuritogenesis in BU-1 cells. A significant reduction of the euxanthone-induced neuritogenic effect was also observed when the PKC isoform-specific inhibitor Go6976 was included in the culture. These results suggest that the euxanthone-induced differentiation of the neuroblastoma BU-1 cells may be mediated through the differential expression of PKC-alpha, -beta, -delta, -lambda and -zeta isoforms.

Community study of depression in old age in Taiwan: prevalence, life events and socio-demographic correlates.

BACKGROUND: Published studies of prevalence of depression in old age in Taiwan have yielded equivocal results. AIMS: To study the prevalence of depressive disorders among community-dwelling elderly; further, to assess socio-demographic correlates and life events in relation to depression. METHOD: A randomised sample of 1500 subjects aged 65 and over was selected from three communities. Research psychiatrists conducted all assessments using the Geriatric Mental State Schedule. The diagnosis of depression was made with the GMS-AGECAT (Automated Geriatric Examination for Computerised Assisted Taxonomy); data on life events were collected with the Taiwanese version of the Life Events and Difficulties Schedule. RESULTS: One-month prevalence of psychiatric disorders was 37.7%, with 15.3% depressive neurosis and 5.9% major depression. A high risk of depressive disorders was found among widows with a low educational level living in the urban community, and among those with physical illnesses. CONCLUSIONS: Contrary to most previous reports, we found that the prevalence of depressive disorders among the elderly in the community in Taiwan is high and comparable to rates reported in some studies of UK samples.

Cutaneous oozing of lymphatic fluid after interventional cardiac catheterization in a patient with Noonan syndrome.

A 15-year-old girl with Noonan syndrome, intestinal lymphangiectasia and severe valvar pulmonary stenosis had an abnormal lymphangioscintigram that showed intense activity in the inguinal regions bilaterally. Cutaneous oozing of lymphatic fluid from the groin wound complicated percutaneous balloon pulmonary valvoplasty. This previously unreported complication highlights the risk of damage to abnormal lymphatic channels in patients with Noonan syndrome who undergo interventional catheterization.

Validation of the Chinese Health Questionnaire (CHQ-12) in community elders.

There has been no validated screening instrument for use in non-psychotic illness of the elderly in Taiwan. This study aims to test the validity of the 12-item Chinese Health Questionnaire (CHQ-12) among the elderly in a community study. The CHQ-12 was administrated via reading-out to 222 subjects aged 65 and over from three communities. Psychiatrists using the Geriatric Mental Status Schedule (GMS) assessed psychiatric condition while the diagnosis was made according to the computerized program, AGECAT. Validity indices of the CHQ-12 were calculated, using the Relative Operating Characteristic (ROC) analysis for its optimal cut-off point. Variables hypothesized to affect its performance were assessed. Validity of the CHQ-12 at optimal cut-off point 2/3 were estimated with a sensitivity of 79.7%, a specificity of 83.6%, a positive predictive value of 68.9%, a negative predictive value of 90.0% and an overall misclassification rate of 17.6%, and an estimate of the area under the ROC curve of 0.81. The performance of the CHQ-12 was better in males, in those who were literate, and in those without any physical illness. This study demonstrated that the use of CHQ-12 in the elderly community is as valid as in the general population survey. However, it should be read out by the investigator rather than self-administered due to the high proportion of illiteracy among the Taiwanese elderly.