Kiran Bala

Institute of Human Behaviour & Allied Sciences, Old Delhi, NCT, India

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Publications (26)33.17 Total impact

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    ABSTRACT: Background: Even with numerous studies the cause of Parkinson's disease (PD) remains elusive. It has been hypothesized that interactions between genetic and environmental factors may play an important role in the pathogenesis of PD. Objectives: To examine the gene-gene and gene-environment interaction on PD risk with respect to gene polymorphism of cytochrome P450 2D6 (CYP2D6) and glutathione S-transferases pi 1 (GSTP1), organochlorine pesticides (OCPs) and metals. Methods: This study included 70 patients of PD and 100 age-matched controls. The restriction fragment length polymorphism was used for analysis of genetic polymorphism. OCPs and serum metal levels were estimated by using gas chromatography and an autoanalyser respectively. Results: The CYP2D6*4 mt and GSTP1 *B allelic variants were significantly associated with increase in PD risk. We found a statistically significant difference in β-hexachlorocyclohexane (β-HCH), dieldrin, 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (pp'-DDE) and copper levels between the patients and controls. We found significantly high levels of β-HCH, dieldrin and pp'-DDE in the CYP2D6*4 mt allelic variants, β-HCH and pp'-DDE in the GSTP1*B allelic variants and dieldrin in the GSTP1*C allelic variants when comparing CYP2D6*4 non-mt, GSTP1 non-*B and GSTP1 non-*C allelic variants in patients of PD respectively. Conclusion: This study demonstrates that the CYP2D6*4 and GSTP1 genes may be considered as candidate genes for PD and they may also interact with β- HCH, dieldrin and pp'-DDE to influence the risk for PD.
    Current Aging Science 08/2014;
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    ABSTRACT: Changes in lifestyle habits such as diet modification or supplementation have been indicated as probable protective factors for a number of chronic conditions including Alzheimer's disease (AD). With this background, we aim to hypothesize that whether C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene contributes towards the risk of developing AD and its association with vitamin B12 and folate levels.
    Annals of Indian Academy of Neurology 07/2014; 17(3):308-12. · 0.93 Impact Factor
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    ABSTRACT: It has been assumed that the association between Alzheimer disease (AD) and pesticides may be stronger among genetically susceptible individuals. The aim of the study was to examine the genetic polymorphism in cytochrome P450 2D6 (CYP2D6) and glutathione S-transferases pi 1 (GSTP1) with respect to organochlorine pesticides (OCPs) and metals in AD. This study included 100 patients with AD and 100 age-matched controls. The genetic polymorphisms were analyzed by restriction fragment length polymorphism. The OCPs and serum metal levels were determined using gas chromatography and an autoanalyzer, respectively. We found a statistically significant association between AD and high levels of β-hexachlorocyclohexane (β-HCH; odds ratio [OR] = 2.064, 95% confidence intervals [95% CIs] = 1.373-3.102, dieldrin [OR = 2.086, 95% CI = 1.224-3.555], and copper [OR = 1.038, 95% CI = 1.012-1.064). The significant low level of magnesium (OR = 0.151, 95% CI = 0.047-0.489) even appears to have a protective role against AD. The GSTP1*B (P = .009) and GSTP1*C (P = .011) allelic variants were associated with increase in AD risk. This study demonstrates that the GSTP1*B and *C allelic variants may be considered a candidate gene for AD. It can be suggested that although CYP2D6*4 polymorphism is not a risk of AD, the CYP2D6*4 and GSTP1 polymorphism may interact with β-HCH, dieldrin, and copper to influence the risk of AD.
    Journal of Geriatric Psychiatry and Neurology 02/2014; · 3.53 Impact Factor
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    ABSTRACT: Epidemiologic findings suggest that lipids and alteration in lipid metabolizing protein/gene may contribute to the development of neurodegenerative disorders. The aim of the current study was to determine the serum lipid levels and genetic variation in two lipid metabolizing genes, low-density lipoprotein receptor-related protein-associated protein (LRPAP1) and apolipoprotein E (APOE) gene in Parkinson's disease (PD). Based on well-defined inclusion and exclusion criteria, this study included 70 patients with PD and 100 age-matched controls. LRPAP1 and APOE gene polymorphism were analyzed by polymerase chain reaction and restriction fragment length polymorphism, respectively. Fasting serum lipid levels were determined using an autoanalyser. The logistic regression analysis showed that high levels of serum cholesterol [odds ratio (OR) = 1.101, 95 % confidence interval (CI95%) = 1.067-1.135], LRPAP1 I allelic variant alone (OR = 2.766, CI95% = 1.137-6.752) and in combination with APOE ε4 allelic variant (OR = 4.187, CI95% = 1.621-10.82) were significantly associated with increase in PD risk. Apart from that, the high levels of LDL cholesterol appears to have a protective role (OR = 0.931, CI95% = 0.897-0.966) against PD. The LRPAP1 I allelic variant may be considered a candidate gene for PD, predominantly in patients having the APOE ε4 allelic variant.
    Neurological Sciences 02/2014; · 1.41 Impact Factor
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    ABSTRACT: Organophosphate (OP) poisoning is a common occurrence in the rural areas of developing countries like India. Acute cholinergic crisis is one of the important causes of mortality related to OP poisoning. Delayed peripheral neuropathy, extrapyramidal syndromes and neuropsychiatric manifestations are the major consequences of secondary neuronal damage. This case illustrates a 14-year-old girl who ingested 50 mL of OP pesticide and developed extrapyramidal symptoms in the form of parkinsonism and hand dystonia in spite of immediate medical attention. MRI of the brain with T2, fluid attenuated inversion recovery and diffusion-weighted sequences revealed bilateral symmetrical basal ganglia hyperintensities. Further follow-up revealed a significant clinical improvement with marked resolutions of the brain lesions. The reversible extrapyramidal symptoms with disappearance of neuroimaging findings without neuropathy or neuropsychiatric manifestations are unusual in OP poisoning.
    Case Reports 01/2014; 2014.
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    ABSTRACT: The notion of potential existence of gene environment interaction (GxE) in Alzheimer’s disease (AD) has substantial impact on understanding the role of genetic and non-genetic contribution to this disorder. Keeping in mind this background we examined the genetic and environmental factors which may determine their relative contribution to AD. Based on well defined inclusion and exclusion criteria this study includes 70 AD patients and 75 age-matched controls. Organochlorine Pesticides (OCPs) were analyzed in blood by using gas chromatography and serum metals were analyzed by using an autoanalyser. The LRPAP1 and APOE gene polymorphism were determined by polymerase chain reaction and restriction fragment length polymorphism respectively. The frequency of APOE ε4 allele and LRPAP1 I allele were significantly high (p=0.000 for both allele) in AD patients as compared to controls. The significantly high levels of β-hexachlorocyclohexane (β-HCH) and dieldrin are risk factors for AD independent of the genetic risk factor, recording an odds ratio of 2.777 and 2.344 respectively. This study suggests that out of the environmental factors, high β-HCH levels were the best predictor of presence of AD independent of the genetic component and low levels of serum iron play a protective role against AD.
    American Journal of Alzheimer’s Disease. 07/2013; 1(1):60-71.
  • SNCI-2013; 02/2013
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    ABSTRACT: The cause of Parkinson's disease (PD) remains elusive, but environmental chemical exposures have been postulated to be involved in the etiology of PD. We examined the association between the persistent organochlorine pesticides (OCPs) and PD in the North Indian population. This case control study included 70 PD and 75 control subjects in the age group of 50 to 85 years. Blood samples were collected and high-purity grade hexane and acetone (2 : 1 ratio) were used for extraction of organochlorine residues. OCPs (hexachlorocyclohexane (HCH), aldrin, dieldrin, endosulfan, pp'-Dichlorodiphenyldichloroethylene (pp'-DDE), op'-DDE, pp'- Dichlorodiphenyltrichloroethane (pp'-DDT), op'-DDT, pp'-dichlorodiphenyldichloroethane (pp'-DDD) and op'-DDD) were quantitatively estimated by using gas chromatography. The most frequently detected OCP was dieldrin, which was present in 9.3% of control and 61.4% of PD. The strongest predictor was β-hexachlorocyclohexane (β-HCH), which reported an odds ratio of 2.566, indicating that for every additional one unit of β-HCH, patients had 2.566 times more chances of presence of PD. This study indicates that increased level of β-HCH and dieldrin may be associated with the risk of PD.
    ISRN neurology. 01/2013; 2013:371034.
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    ABSTRACT: Objectives: The aim was to examine the gene environment (GxE) interaction with reference to APO E genotypes, serum lipids and organochlorine pesticides (OCPs) as one of the factors in the etiology of Alzheimer's disease (AD). Methods: A case control study was used to examine, APOE HhaI polymorphism by polymerase chain reaction (PCR)/PCRrestriction fragment length polymorphism method, serum lipids by autoanalyser and OCPs by gas chromatography (GC). Results: APOE ∈4 allele frequency was significantly high (p=0.000, OR=5.73, CI=2.68-12.50) in AD as compared to controls. The serum cholesterol, β- hexachlorocyclohexane and dieldrin are risk factors for AD independent of the APOE ∈4 risk allele, recording an odds ratio of 1.16, 11.38 and 10.45 respectively. Conclusion: GxE interactions exist with APOE ∈4 allele status that need to be considered for the study design and analysis of such data in future studies of AD.
    American Journal of Alzheimer s Disease and Other Dementias 08/2012; 27(7):496-503. · 1.52 Impact Factor
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    ABSTRACT: Alzheimer's disease (AD) could result from a multifactorial process involving both genetic predisposition and exposure to environmental factors like pesticides. A case control study of 70 patients of AD and 75 controls was done to examine the association between organochlorine pesticides (OCPs) and risk of AD. OCPs (hexachlorocyclohexane (HCH), aldrin, dieldrin, endosulfan, pp'-dichlorodiphenyldichloroethylene (pp'-DDE), op'-DDE, pp'-dichlorodiphenyltrichloroethane (pp'-DDT), op'-DDT, pp'-dichlorodiphenyldichloroethane (pp'-DDD) and op'-DDD) were extracted from blood and quantitatively estimated using gas chromatography. A Mann-Whitney U test revealed significant difference in β-HCH levels (U = 1237.00, W = 4087.00, z = -6.296, p = 0.000, r = -0.71), dieldrin levels (U = 1449.00, W = 4299.00, z = -5.809, p = 0.000, r = -0.68) and pp'-DDE levels (U = 2062.00, W = 4912.00, z = -2.698, p = 0.007, r = -0.59) between AD patients and controls. In conclusion, this study supports epidemiological studies that associate exposure to pesticides with increased risk of AD, and we identified the specific pesticides β-HCH, dieldrin and pp'-DDE that are associated with the risk of AD in the north Indian population. However, further research is needed to establish the potential role of these OCPs as an etiologic agent for AD case.
    Human & Experimental Toxicology 08/2012; · 1.31 Impact Factor
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    ABSTRACT: The ATP-binding cassette (ABC) superfamily of transporters is known to efflux antiepileptic drugs (AEDs) primarily in the brain, gastrointestinal tract, liver, and kidneys. In addition, they are also known to be involved in estrogen disposition and may modulate seizure susceptibility and drug response. The objective of the present study was to investigate the role of genetic variants from ABC transporters in seizure control in epilepsy patients treated with monotherapy of first-line AEDs for 12 months. On the basis of gene coverage and functional significance, a total of 98 single nucleotide polymorphisms from ABCB1, ABCC1, and ABCC2 were genotyped in 400 patients from North India. Of these, 216 patients were eligible for therapeutic assessment. Genetic variants were compared between the 'no-seizures' and the 'recurrent-seizures' groups. Bonferroni corrections for multiple comparisons and adjustment for covariates were performed before assessment of associations. Functionally relevant promoter polymorphisms from ABCC2: c.-1549G>A and c.-1019A>G either considered alone or in haplotype and diplotype combinations were observed for a significant association with seizure control in women (odds ratio>3.5, P<10, power>95%). Further, low protein-expressing CGT and TGT (c.-24C>T, c.1249G>A, c.3972C>T) haplotypes were always observed to be present in combination with the AG (c.-1549G>A, c.-1019A>G) haplotype that was over-represented in women with 'no seizures'. The distribution of the associated variants supports the involvement of ABCC2 in controlling seizures in women possibly by lowering of its expression. The biological basis of this finding could be an altered interaction of ABCC2 with AEDs and estrogens. These results necessitate replication in a larger pool of patients.
    Pharmacogenetics and Genomics 06/2012; 22(6):447-65. · 3.61 Impact Factor
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    ABSTRACT: This article briefly outlines the proposed national epilepsy control program. The content of the article is based on four meetings held by invitation of the Ministry of Health. Invitees by ministry - Drs. D. C. Jain, M. Gourie Devi, V. Saxena, S. Jain, P. Satish. Chandra, M. Gupta, K. Bala, V. Puri, K. S. Anand, S. Gulati, S. Johri, P. S. Chandra, M. Behari, K. Radhakrishnan, D. Bachani. Presentations were made by Dr. M. Tripathi.The program will involve all neurologists across the country in teaching and training at state levels and a central monitoring committee.
    Annals of Indian Academy of Neurology 04/2012; 15(2):89-93. · 0.93 Impact Factor
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    ABSTRACT: It is hypothesized that functionally relevant polymorphisms in genes encoding metabolizing enzymes of sex steroids may influence drug response by directly predisposing women with epilepsy to seizure exacerbation. An alteration in estradiol:progesterone ratio is believed to play a role in seizure occurrence in women. CYP1A1 is a key enzyme involved in the metabolism of estradiol, with variants of the CYP1A1 gene having been reported to play a role in the alteration of sex hormone metabolism in women. The objective of the present study was to test for the association of genetic variants in CYP1A1 with seizure recurrence in patients diagnosed with epilepsy. In the study, the association of five variants in CYP1A1 with seizure control in 228 patients with epilepsy on first-line antiepileptic drug therapy for a minimum period of 12 months was investigated. A significant association of an intronic SNP, IVS1 +606C>A (rs2606345), with respect to seizure recurrence (genotypic: p = 3.3 × 10(-4); allelic: p = 7.2 × 10(-4); OR: 2.86; 95% CI: 1.5-5.3) in women with epilepsy from North India was observed. Since CYP1A1 is not involved in the metabolism of any of the first-line antiepileptic drugs, these results imply that variants from genes encoding sex hormone metabolizing enzymes might act as markers for predicting response to antiepileptic drug therapy in women with epilepsy.
    Pharmacogenomics 11/2010; 11(11):1525-34. · 3.86 Impact Factor
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    ABSTRACT: Variability in the physiological levels of neuroactive estrogens is widely believed to play a role in predisposition to several disorders of the central nervous system. Local biosynthesis of estrogens in the brain as well as their circulating serum levels are known to contribute to this pool of neuroactive steroids. It has been well accepted that estrogens modulate neuronal functions by affecting genesis, differentiation, excitability, and degeneration of nerve cells. These actions of estrogens appear to be more prominent in females with higher concentrations and marked variability of circulating serum levels occurring over a woman's lifetime. However, our knowledge regarding the variability of neuroactive steroid levels is very limited. Furthermore, several studies have recently reported differences in the synchronization of circulating and neuronal levels of estradiol. In the absence of reliable circulating steroid levels, knowledge of genetic variability in estrogen disposition may play a determining factor in predicting altered susceptibility or severity of neuropsychiatric disorders in women. Over the past decade, several genetic variants have been linked to both differential serum estrogen levels and predisposition to diverse types of neuropsychiatric disorders in women. Polymorphisms in genes encoding estrogen-metabolizing enzymes as well as estrogen receptors may account for this phenotypic variability. In this review, we attempt to show the contribution of genetics in determining estrogenicity in females with a particular emphasis on the central nervous system. This knowledge will further provide a driving force for unearthing the novel field of "Estrogen Pharmacogenomics." © 2010 Wiley-Liss, Inc.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 09/2010; 153B(8):1391-410. · 3.23 Impact Factor
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    ABSTRACT: Over-expression of efflux transporter P-glycoprotein (PgP) encoded by ABCB1 gene has been implicated in poor responsive epilepsy. Several genetic variants have been shown to influence the expression levels of P-glycoprotein. The aim of the present study was to investigate the role of ABCB1 polymorphisms: C1236T, G2677T/A and C3435T in determining drug response to first line antiepileptic drugs (AEDs) namely phenobarbitone, phenytoin, carbamazepine and valproate in North Indian cohort of epilepsy patients. DNA samples were obtained from 392 consecutive epilepsy patients, out of which 228 had completed follow-up evaluation at 12 months. After attaining steady state of the AEDs in the first two months of study, 133 patients showed complete freedom from seizures (no-seizure group) and 95 patients continued to have seizures (recurrent-seizures group) in the remaining period of study. Comparison of "no-seizure" and "recurrent-seizures" groups revealed no significant differences in allelic, genotypic and haplotypic frequencies for all the studied variants. In conclusion, our finding disproves a general association between ABCB1 polymorphisms and drug response in epilepsy patients.
    Biochimie 09/2010; 92(9):1207-12. · 3.14 Impact Factor
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    ABSTRACT: The first-line antiepileptic drugs, although affordable and effective in the control of seizures, are associated with adverse drug effects, and there is large interindividual variability in the appropriate dose at which patients respond favorably. This variability may partly be explained by functional consequences of genetic polymorphisms in the drug-metabolizing enzymes, such as the CYP450 family, microsomal epoxide hydrolase and UDP-glucuronosyltransferases, drug transporters, mainly ATP-binding cassette transporters, and drug targets, including sodium channels. The purpose of this study was to determine the allele and genotype frequencies of such genetic variants in patients with epilepsy from North India administered first-line antiepileptic drugs, such as phenobarbitone, phenytoin, carbamazepine and valproic acid, and compare them with worldwide epilepsy populations. SNP screening of 19 functional variants from 12 genes in 392 patients with epilepsy was carried out, and the patients were classified with respect to the metabolizing rate of their drug-metabolizing enzymes, efflux rate of drug transporters and sensitivity of drug targets. A total of 16 SNPs were found to be polymorphic, and the allelic frequencies for these SNPs were in conformance with Hardy-Weinberg equilibrium. Among all the polymorphisms studied, functional variants from genes encoding CYP2C19, EPHX1, ABCB1 and SCN1A were highly polymorphic in North Indian epilepsy patients, and might account for differential drug response to first-line antiepileptic drugs. Interethnic differences were elucidated for several polymorphisms that might be responsible for differential serum drug levels and optimal dose requirement for efficacious treatment.
    Pharmacogenomics 07/2010; 11(7):927-41. · 3.86 Impact Factor
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    ABSTRACT: Stigmatized psychosocial perception poses a serious challenge and source of discrimination which impedes epilepsy patients from attaining a satisfactory quality of life. The present study was aimed to obtain information on knowledge, attitudes and practices (KAP) of epilepsy patients in Delhi and compare with the published data from India. We included 120 people with epilepsy (PWE) attending the Neurology outpatient services of the Institute of Human Behavior and Allied Sciences (IHBAS), Delhi. Demographic details and responses to a questionnaire assessing the knowledge, attitude and practices were recorded. Although majority of the patients belonged to low socioeconomic strata, the literacy rate was reasonably high (70%). A large majority (94%) of PWE had heard about epilepsy and 91% knew that epilepsy can be treated with modern drugs. Positive attitude was observed with respect to allowing a child with epilepsy to study (80%), not objecting children to play with a child with epilepsy (95%), marriage (89%) and having children (92%). Negative attitude was refl ected in the belief that epilepsy is due to supernatural powers (16%) and sins committed by patient or ancestors (21%). Analysis of Indian data revealed regional differences in KAP which could be attributed to local factors, such as literacy, awareness about epilepsy, and practice of different systems of medicine. Some of the differences can also be attributed to category of study population whether it included patients or non epilepsy individuals, since the former are likely to have less negative attitudes than the public. There is a need to create awareness about epilepsy on a nation-wide basis to dispel the misconceptions and stigma through effective and robust programs with the aim to lessen the disease burden.
    Neurology Asia 01/2010; 15:225-232. · 0.15 Impact Factor
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    ABSTRACT: The present study was conducted to assess correlation of ammonia levels with valproate levels in epileptic patients presenting with valproate toxicity and also whether liver enzymes and ammonia levels could serve as biochemical marker of valproate toxicity. 100 patients with epilepsy who had received valproate therapy for more than 12 months and had presented with valproate toxicity and 100 controls were included in the study. The serum valproate, ammonia and liver enzymes were measured in these subjects. In patients with valproate toxicity, the mean level of serum valproate was 110.91 ± 28.68 mg/dL (therapeutic range 50-100 mg/dL). Serum ammonia was higher (86.37 ± 39.90 µg/dL) in patients with valproate toxicity compared to controls (68.73 ± 30.07 µg/dL). Out of 100 patients, only 37 patients had serum valproate level > 120 mg/dL and 22 patients had raised levels of valproate as well as ammonia. Age < 30 years and serum ammonia > 69 μg/dL is risk factors for valproate toxicity. Serum ammonia, liver enzymes should be regularly investigated in patients on valproate therapy for early diagnosis of valproate toxicity.
    Indian Journal of Clinical Biochemistry 10/2009; 24(4):366-9.
  • Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2009; 5(4).
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    ABSTRACT: A retrospective study was conducted to assess the appropriateness of the utilization of therapeutic drug monitoring (TDM) services with regards to antiepileptic drugs (AEDs) at a tertiary care hospital, and analysis of 5094 samples of the carbamazepine (CBZ), phenytoin (PHT), valproic acid (VAP), and phenobarbitone (PB) was undertaken. Maximum requisitions were received for CBZ (54.92%) followed by PHT (27.05%), VAP (14.40%), and PB (3.61%). About 2.12% requisitions were received for patients taking unlabeled AEDs. Reasons for TDM were routine monitoring (36.3%), adverse drug reactions (ADRs) (17.2%), relapse (30.7%), no response (3.35%), and irregular treatment (2.24%) and not mentioned (10.5%). Majority of the samples (69%) were drawn for measuring trough levels; however, in 22% time of last dose was not mentioned and 9.64% were for peak or random levels. In all, 6.9% requisitions for TDM were sent before steady-state levels, and in 15.5% duration of therapy was not mentioned. Blood levels within therapeutic range were found with CBZ (63%) followed by PB (56.52%), VAP (45.99%), and PHT (42.52%). Blood levels were above therapeutic range in 45.69%, 29%, and 21.73% patients taking VAP, PHT, and PB, respectively. Unsuspected poor compliance was uncovered in 11.8%, 41.2%, and 29.3% requisitions sent with ADR, relapse, and routine monitoring as reason for drug levels, respectively. Only half of all AED measurement requisitions were complete and met the criteria for appropriate AED-level determination. Incomplete requisitions lead to difficulty in uniform interpretation of results and thus add to unnecessary costs.
    American Journal of Therapeutics 01/2009; 16(1):11-6. · 1.29 Impact Factor