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Biomedical subjects

R Mahendran

Publications and source records attributed to R Mahendran.

At least 19 recordsLinked to original sources

Susceptibility to neuroleptic-induced tardive dyskinesia and the T102C polymorphism in the serotonin type 2A receptor.

BACKGROUND: Genetic factors have been implicated in the pathophysiology of the movement disorder tardive dyskinesia, which may involve dopamine-serotonin interaction. Case-control association studies have identified the T102C polymorphism of the 5-HT2A receptor gene as being associated with schizophrenia and responsiveness to clozapine. In this study, we examine the association of this polymorphism in the 5-HT2A receptor gene as a risk factor for developing schizophrenia and tardive dyskinesia from prolonged treatment with neuroleptics. METHODS: Ninety-seven healthy control subjects with no history of mental illness and 221 schizophrenic patients (87 with tardive dyskinesia, 134 without) were genotyped by PCR-RFLP. RESULTS: Comparison between cases and control subjects revealed no significant association between the C allele and schizophrenia. There was significant difference in allele frequency (p = .044, OR = 1.54 95% CI = 1.02-2.33) between patients who developed tardive dyskinesia and those who did not. Significant difference remains even after adjusting for age and neuroleptic dosage (p = .041) with the odds ratio at 1.64 (95% CI = 1.02-2.62). CONCLUSIONS: A genetic variant of the 5-HT2A receptor may be associated with neuroleptic-induced tardive dyskinesia in schizophrenia. Further studies are needed to replicate the finding. The role of 5-HT2A receptor in the etiology of tardive dyskinesia or treatment-resistant schizophrenia should be further investigated.

Antipsychotic Agents↗

Transfection of urothelial cells using methyl-beta-cyclodextrin solubilized cholesterol and Dotap.

the murine urothelial cell line, mb49 was transfected with the reporter gene pcmvlacz using a number of commercial transfection agents. the transfection efficiency of these agents, as determined by beta-galactosidase activity, is in the order of dotap>superfect>Fugene. The addition of methyl-beta-cyclodextrin solubilized cholesterol (MBC) to Dotap and Superfect further improved their transfection efficiency by 3.8-fold and 2.6-fold, respectively. beta-Galactosidase activity was detectable within 1 h of transfection and peaked at 48 h. Nuclear and cytoplasmic separation showed that with Dotap + methyl-beta-cyclodextrin solubilized cholesterol (DMBC), the DNA plasmid complex was found in both the nucleus and the cytoplasm. In vivo, murine bladders were transfected with an intravesical instillation of DMBC + DNA for 2 h. Two days later the bladder, lungs, liver, spleen and heart were assayed for the presence of the beta-galactosidase gene by staining and PCR. Expression of the gene was confined to the bladder. Both in vitro and in vivo expression was observed after as little as a 15 min exposure to DMBC:DNA. Expression of the marker gene was present up to 30 days after transfection in vivo. From our data it appears that DMBC is the best nonviral agent for the transfection of urothelial cells in vitro and in vivo.

Animals↗

Mental health literacy survey of psychiatrically and generally trained nurses employed in a Singapore psychiatric hospital.

Mental health literacy studies consider the capacity of respondents to recognize certain psychiatric disorders, judge the comparative utility of a range of interventions, and make estimates about outcome and prognostic issues. We report such a study involving a sample of nursing staff employed at a large psychiatric institution in Singapore, and who were provided with separate brief vignettes of mania, schizophrenia and depression. Subjects were highly accurate in 'diagnosing' schizophrenia, less accurate for depression and even less accurate in diagnosing mania. Depression was alternately diagnosed as stress, mania was most commonly misdiagnosed as schizophrenia, and for both psychotic conditions, a percentage returned non-psychotic diagnoses. In terms of treatment options, staff distinctly favoured a 'medical model' and viewed traditional and alternative healing options as distinctly harmful. Analyses contrasted psychiatrically trained and generally trained nurses, but identified few significant differences. Such information has the potential to shape the education and training of mental health professional staff, as well as provide important insights about how nurses may diagnose, view and favour alternative treatments and strategies to assist those with common psychiatric disorders.

Data Collection↗

Awareness of tardive dyskinesia in Asian patients with schizophrenia.

While ethnocultural differences in risk of tardive dyskinesia (TD) have been suggested, no previous studies have examined whether this factor also plays a role in lack of awareness of TD. This study examined this question in an Asian population with schizophrenia. Six hundred seven patients in a state mental hospital in Singapore were assessed using the Abnormal Involuntary Movement Scale (AIMS) and the Simpson-Angus Rating Scale. Of the 607 patients, 242 (39.9%) met criteria for TD, and 163 (67.4%) patients were not aware of the presence of TD. No significant differences in terms of age, gender, and duration of illness were found between those aware of their TD and those not aware. Daily neuroleptic doses and scores for the AIMS and Simpson-Angus Rating Scale were significantly different, although after logistic regression, only the Simpson-Angus Rating Scale scores remained significant. The finding that a large proportion of our patients lacked awareness of their TD is consistent with other reports in the West and provides evidence that this feature is characteristic of the illness rather than of a specific ethnocultural group. We found an association between lack of awareness and greater severity of extrapyramidal symptoms (EPS), suggesting that there may be a subtype of TD in which lack of awareness and greater vulnerability of developing EPS are features.

Adult↗

Characteristics of patients referred to an insomnia clinic.

AIM: To study the socio-demographic profile, symptomatology, prior treatment and treatment response of patients seen in an Insomnia Clinic. METHOD: Information was gathered by case-note review from eighty-five consecutive cases referred to the clinic. FINDINGS: There were almost equal numbers of males and females and they were predominantly Chinese, married and almost equally distributed in the 31 to 60 years age range. More than half (54.2%) had sleep problems for more than a year and almost three quarters (74.1%) had prior treatment for sleep problems. The main presenting complaints were of difficulty initiating sleep (92.9%). About 60.7% reported that their sleep problems were transient episodes and 39.3% reported it as persistent. 92.9% of the cases received pharmacotherapy. All patients received psychological treatment. For those treated with pharmacotherapy, 44.7% received benzodiazepines and 37.6% received non-benzodiazepine hypnotics. The majority, 77.5% were on treatment for less than six months. 48.2% improved and ended treatment themselves. CONCLUSIONS: The patients in this sample sought treatment or were referred for treatment much earlier compared to other samples studied. Importantly, 29.5% of the patients referred had an undiagnosed psychiatric condition.

Adult↗

Risperidone in the treatment of first episode psychosis.

OBJECTIVE: To evaluate the efficacy and safety of risperidone in Singapore patients with first-episode psychosis in an eight-week open label prospective study. METHOD: Previously untreated male and female patients aged 18 - 65 with DSM IV schizophreniform disorder or DSM IV schizophrenia for no longer than 12 months were recruited from Woodbridge Hospital and Geylang Psychiatric Outpatient Clinic. Patients were treated with risperidone for 56 days. Outcome was assessed with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression scale (CGI). Safety was assessed by monitoring of vital signs and by comparing the frequency of adverse events (AEs) before and after treatment. RESULTS: 24 patients with a mean age of 33.29+/-9.12 years and a mean duration of illness of 166.5+/-111.4 days (median 180 days) were included. The mean risperidone dosage was 2.7 mg +/- 1.0 at day 56. Mean PANSS total scores reduced by 50.21% from 88.29+/-21.55 at baseline to 43.96+/-7.5 at endpoint (p < 0.001). The responder rate (> or = 20% reduction in the total PANSS score) was 87.5%. 13 patients (54.2%) exhibited a 50% or greater reduction in total PANSS score. Except for item G5 (mannerisms and posturing) all single PANSS items were reduced significantly. The CGI scores of all patients improved at endpoint. No serious adverse events were reported. CONCLUSIONS: Overall the therapy of first-episode psychosis patients with risperidone was effective and safe.

Adult↗

Cardiac effects of psychotropic drugs.

INTRODUCTION: The incidence of mortality is higher among psychiatric patients than among the general population and the cause of which may be the psychiatric disorder itself or other related factors like life-style and medications. Sudden death has been associated with certain psychotropic drugs and the underlying cause(s) have been suggested to be some adverse cardiac complications. We reviewed the literature for the cardiac effects attributed to psychotropic drugs. METHODS: A Medline and manual search of the literature on the cardiac effects attributed to the psychotropic drugs was performed. We limited ourselves to the main psychotropic drugs (antipsychotics, antidepressants, mood stabilizers, and benzodiazepines) that are available in Singapore. RESULTS: The search showed that certain drugs carry a greater potential for adverse cardiac complications. Among the antipsychotics, thioridazine has a greater risk for cardiac events. The tricyclic antidepressants also have significant effect on the heart rate, blood pressure as well as having the propensity to cause prolonged QTc, whereas the selective serotonin reuptake inhibitors (SSRIs) are generally safe. Among the mood stabilizers, lithium and carbamazepine have been associated with sinus node arrhythmias while sodium valproate is relatively free of any untoward cardiac effect. The benzodiazepines are in general safe even in patients with myocardial infarction and coronary bypass. CONCLUSIONS: In patients with higher risk of cardiac complications (elderly, pre-existing cardiac disorders, concurrent medications with potential cardiac effects and poor metabolizers), the choice of psychotropic drugs where indicated has to be considered with these factors in mind as well as the inherent risk of these psychotropic drugs. Monitoring of the blood pressure, heart rate and ECG should be done regularly.

Arrhythmias, Cardiac↗

Neuroleptic and anticholinergic drug use in Chinese patients with schizophrenia resident in a state psychiatric hospital in Singapore.

OBJECTIVE: The objective of this study was to survey the prescribing pattern in Chinese patients with chronic schizophrenia in a state mental hospital in Singapore, and to compare our findings with those of surveys of Chinese patients in other countries. METHOD: We surveyed the use of neuroleptic and anticholinergic agents among Chinese patients with chronic schizophrenia (n = 534) in a state mental hospital in Singapore. RESULTS: Fifty-nine per cent of the patients received two or more neuroleptics (median daily dose of 400 mg chlorpromazine equivalents, range 50-2875 mg). There were no differences in gender distribution between those prescribed multiple neuroleptics as against an older group of those receiving none or only one neuroleptic medication. Sixty-six per cent of the patients were receiving depot neuroleptics, with more than half of these subjects also receiving additional oral neuroleptics. Patients who were prescribed multiple neuroleptics received significantly higher total doses than those receiving just one neuroleptic. Only 1% of patients were prescribed an atypical neuroleptic. Sixty-five per cent of patients were prescribed an anticholinergic agent. Those prescribed anticholinergic agents were younger, in receipt of higher doses of neuroleptic medications and had lower Simpson-Angus scores for extrapyramidal side-effects. CONCLUSIONS: The pervasive use of multiple typical neuroleptics, marked underutilisation of atypical neuroleptics, and the lack of anticholinergic medication in patients who might benefit from such treatment are issues of substantial concern, warranting action in both psychiatry practice and mental health policy.

Adult↗

Season of birth in schizophrenia: no latitude at the equator.

BACKGROUND: If the established winter excess in births of people who subsequently develop schizophrenia is an effect of 'seasonality', this would be testable by examining the pattern of births in an equatorial region with no formal seasons. AIMS: To investigate whether there is any variation in month of birth among patients from equatorial Singapore with a diagnosis of schizophrenia. METHOD: All 9655 patients discharged from Singapore's national psychiatric hospital with a diagnosis of schizophrenia were included (year of birth range 1930-1984). We analysed aggregated data, as well as the data of subsamples grouped according to birth-year periods, in order to examine secular trends. One patient subsample (those born 1960-84) allowed exact matching against the general population data set and close testing of any seasonal influence. RESULTS: Monthly variation in births was evident for both patients and controls; the patterns were very similar, apart from the patient sample showing a trough in March-April. CONCLUSIONS: In an equatorial region, where 'seasons' are absent, no seasonal excess in births of those later developing schizophrenia was evident.

Adult↗

Contrasting clozapine prescribing patterns in the east and west?

INTRODUCTION: Polypharmacy is common in the treatment of schizophrenia and it may be especially common in the East. In this survey, we compared the effect of clozapine, an atypical neuroleptic, on polypharmacy in two groups of patients with schizophrenia in two different settings. MATERIALS AND METHODS: The medical charts of patients on stable doses of clozapine from a Canadian psychiatric centre and that of a Southeast Asian centre were analysed to evaluate the daily dose requirement and the concomitant medications prescribed. The beliefs of the Asian psychiatrists on the concomitant use of another neuroleptic were also examined. RESULTS: The mean daily dose of clozapine was 408 mg/day for the Canadian subjects and 169 mg/day for the Asian sample. Of the Canadian sample, none were prescribed another neuroleptic, 45% were on a benzodiazepine, and 10% were receiving an anticholinergic agent. The Singapore sample indicated 28% of the subjects on another neuroleptic, with 36% taking an anticholinergic agent and 28% on a benzodiazepine. The Asian psychiatrists prescribed a second neuroleptic in the belief that it would reduce cost and enhance the antipsychotic effect. CONCLUSIONS: This study suggests that there are regional differences in the prescription patterns and daily dose requirements of clozapine.

Adult↗

Obsessive compulsive disorder following left middle cerebral artery infarct.

A case of a 37-year-old male who developed compulsive washing after a massive infarct involving the left middle cerebral artery, is described. Although an obsessive compulsive disorder can occur following neurological disorders,there have been no previous reports of it occurring following a middle cerebral artery infarct.

Adult↗

Editing of cytochrome b mRNA in physarum mitochondria.

The reading frame in the mRNA for the cytochrome b apoprotein in mitochondria of Physarum polycephalum is created by the insertion of 43 nucleotides in the mRNA relative to the mtDNA sequence encoding it (RNA editing). Most of these insertions (31) are single cytidines; however, single uridines are inserted at six sites, and the dinucleotides, CU and GC, are inserted at two sites and one site, respectively. These insertions create a 392-codon reading frame in the mature mRNA. The amino acid sequence inferred from this reading frame has similarity to cytochrome b apoproteins encoded by other mtDNAs. The insertions are quite evenly distributed throughout the length of the reading frame with an average spacing of 27 nucleotides. This mRNA has the highest percentage (23%) of noncytidine insertions of any Physarum RNA characterized to date. cDNAs corresponding to partially edited RNAs can be enriched by selective amplification. Some cDNAs that lack the GC dinucleotide insertion are fully edited at sites flanking the GC dinucleotide insertion site. Similarly some cDNAs lack the CT dinucleotide insertion or have a CC or TT insertion flanked by a fully edited sequence. These results imply that dinucleotide editing occurs by a process separate from the global insertion of cytidines.

Amino Acid Sequence↗

Evaluation of lymphocytic responses after treatment with Bacillus Calmette-Guerin and interferon-alpha 2b for superficial bladder cancer.

Bladder wash-derived lymphocytes from superficial bladder cancer patients involved in high dose BCG, low dose BCG, and low dose BCG with IFN-alpha treatments were examined. We found an increasing trend in the percentage of CD3 T cells with each weekly intravesical instillation and the proportion of CD3 T cells expressing the gammadelta T cell receptor was significantly higher in patients receiving standard dose BCG than those receiving low dose BCG or low dose BCG plus IFN-alpha. Most patients had a predominance of CD4 T cells, while some had more CD8 T cells. The CD4/CD8 ratio did not vary much during the instillations. Surprisingly, both patients and normal control individuals had high percentages of CD69- and CD45RO-positive lymphocytes in the bladder wash and this was not reflected in lymphocytes from peripheral blood collected in parallel. We found no differences in lymphocyte phenotypes, cytokine production, and clinical outcome in the patients from three arms. This may reflect that the qualitative and quantitative immune responses elicited from the three treatments are similar. However, the lymphokine-activated killing ability of peripheral blood lymphocytes against allogeneic cell-lines from the cancer patients was depressed compared to normal individuals and the cytotoxicity appeared to be enhanced after intravesical treatment.

Adult↗

Diagnosis and treatment of mental disorders: a survey of Singapore mental health professionals.

BACKGROUND: A series of surveys of mental health literacy have been undertaken in Australia, involving members of the general public as well as general practitioners and mental health professionals, whereby respondents consider vignettes of depression and of schizophrenia, offer a diagnosis and rate a series of possible interventions for their judged helpfulness. A similar survey was undertaken in Singapore and is reported in this paper. METHODS: The survey was undertaken at a large state psychiatric hospital with staff (psychiatrists, allied health professionals, psychiatrically and generally trained nursing staff) rating a vignette of mania, in addition to the vignettes derived in Australia for depression and schizophrenia, and with the Australian intervention options extended somewhat to respect Singapore facilities. RESULTS: Responses of those in the four professional groups were compared. The psychiatrists were highly accurate in generating diagnoses, other staff somewhat less so for diagnosing depression (with a percentage instead choosing a diagnosis of stress) and mania (with a percentage instead diagnosing a schizophrenic condition). Reported helpfulness ratings identified those interventions judged consensually as likely to be helpful or harmful, as well as establishing some differences across the four professional groups. CONCLUSIONS: The consensus decisions of helpful treatments for depression and schizophrenia revealed very similar findings to judgements made by Australian professionals. The treated outcome of schizophrenia was judged as somewhat worse than that for mania and depression. While non-medical staff differed from psychiatrists in judging the comparative utility of some drug interventions and lifestyle issues, there was clear evidence of a relatively dominant 'medical model' to recommended treatments, while traditional healing practices and services were rated as distinctly unhelpful.

Adult↗