Genetic polymorphisms of CYP2C19 influences the response to clopidogrel in ischemic heart disease patients in the South Indian Tamilian population.

BACKGROUND: The antiplatelet activity of clopidogrel is variable among patients suffering from ischemic heart disease. Variation in the cytochrome P450 2C19 (CYP2C19) gene coding for the CYP2C19 enzyme is one of the major determinants of this variable response to clopidogrel. The activity of the CYP2C19 enzyme, which plays a role in the conversion of the prodrug clopidogrel to its active metabolite, is genetically influenced by polymorphisms in its gene. The aim of our study was to evaluate the association of CYP2C19 polymorphisms and the antiplatelet effect of clopidogrel in the South Indian Tamilian population. MATERIALS AND METHODS: Genotyping and platelet aggregation results of 149 ischemic heart disease patients on clopidogrel maintenance therapy (75 mg daily dose) were analyzed in this study. CYP2C19 polymorphisms were genotyped by the PCR-restriction fragment length polymorphism method. We measured residual platelet activities in these patients on clopidogrel therapy in terms of impedance (expressed as ohms). The study subjects were divided into two metabolizer phenotype groups [group 1: poor/intermediate metabolizers (PM/IM); group 2: extensive/ultra-rapid metabolizers (EM/URM)] based on CYP2C19 genotype, and the residual platelet activities were compared. Higher values of impedance denote increased residual platelet activity. RESULTS: Poor/intermediate metabolizers had significantly higher impedance values than EM/URM [(median; range) 4.0; 0-13 vs. 2.0; 0-11, respectively; p = 0.04]. These higher impedance values denote higher residual platelet activities among the carriers of loss-of-function alleles (CYP2C19*2,*3) than among non-carriers. However, residual platelet activities were lower among the carriers of the gain-of-function allele (CYP2C19*17) than among non-carriers, although this difference was not significant. CONCLUSION: Patients with CYP2C19 (*2 or *3) genetic polymorphisms had higher residual platelet activities and were associated with a reduced antiplatelet response to clopidogrel. As the South Indian Tamilian population is characterized with higher frequencies of these genetic polymorphisms, our findings mandate further studies aimed at initiating genome-based personalized antiplatelet therapy.

Creutzfeldt-Jakob disease.

Cruetzfeldt-Jakob disease is a prion protein disease causing a transmissible, subacute, fatal neurodegenerative disease characterized by a spongiform encephalopathy. Though rare, ever since Pruisner described the pathogenesis in 1982, this disease kept the clinicians as well as biologists spellbound, because of its distinct clinical picture and the novel mechanism of transmission. There was a further quantum leap in the interest in the disease with the establishment of its new clinical variant, the so called 'mad cow disease' in the late 1990s and had led to more stringent measures to ensure the quality of cattle-feeds and cattle-derived food products. The sporadic genetic variants, the commonest form of the disease, continue to challenge the genetic scientists. Advances in neuroimaging, cerebrospinal fluid marker proteins and genetic linkage studies now offer excellent diagnostic methods, while advances in therapeutic medicine which use products from cadaveric extracts such as growth hormone for treatment of hypopituitarism, dural grafts for neurosurgical procedures and cornea for transplantation etc. have thrown new challenges in controlling this serious disease.

Dot-ELISA for the diagnosis of neurocysticercosis.

The aim of the present study was to standardize and evaluate dot-Enzyme linked immunosorbent assay (Dot-ELISA), a simple and rapid test for the detection of cysticercus antibodies in the serum for the diagnosis of neurocysticercosis (NCC). The antigen used in the study was a complete homogenate of Cysticercus cellulosae cysts obtained from infected pigs and dotted on to nitrocellulose membrane. Test sera were collected from the patients of NCC, and control sera from patients with other diseases and healthy students and blood donors of the Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) Hospital, Pondicherry, during a study period from 2001 to 2003. Dot-ELISA detected antibodies in 14 of 25 (56%) in clinically suspected cases of NCC, 13 of 23 (56.5%) in CT/MRI proven cases of NCC and 2 of 25 (8%) each in non-cysticercal CNS infection controls and healthy controls. The test showed a sensitivity of 56.25%, specificity of 92%, positive predictive value of 87.09%, and negative predictive value of 70.76%. Results of the present study shows that the Dot-ELISA as a simple test can be used in the field or poorly equipped laboratories for diagnosis of NCC .

Dot-ELISA for the diagnosis of neurocysticercosis

O objetivo do presente estudo foi estandardizar e avaliar o Dot-ELISA, um teste simples e rápido para detectar anticorpos de cisticercos no soro para diagnóstico da neurocisticercose (NCC). O antígeno usado no estudo foi um homogenizado completo de cistos de Cysticercus cellulosae obtidos de porcos infectados e marcados sobre a membrana de nitrocelulose. Os soros testados foram coletados de pacientes com NCC e os soros controle de pacientes com outras doenças e estudantes saudáveis e doadores e sangue do "Jawaharlal Institute of Postgraduate Medical Education and Research Hospital", em Pondicherry, durante o período de estudo de 2001 a 2003. Dot-Elisa detectou anticorpos em 14 de 25 (56%) casos suspeitos de NCC, em 13 de 23 (56,5%) em CT/MRI casos provados de NCC e em 2 de 25 (8%) cada em controles de infecções do sistema nervoso não devidas à cisticercose e controles saudáveis. O teste mostrou sensibilidade de 56,25%, especificidade de 92%, valor preditivo positivo de 87,09% e valor preditivo negativo de 70,76%. Resultados do presente estudo mostram que o Dot-ELISA como teste simples pode ser usado em trabalhos de campo ou em laboratórios pobremente equipados para o diagnóstico da NCC.

Feasibility of acute thrombolytic therapy for stroke.

BACKGROUND: Thrombolysis is an expensive medical intervention for ischemic stroke and hence there is a need to study the feasibility of thrombolysis in rural India. AIMS: To asses the feasibility and limitations of providing thrombolytic therapy to acute ischemic stroke patients in a rural Indian set-up. MATERIAL AND METHODS: The first 64 consecutive patients registered under the Acute Stroke Registry in a university referral hospital with a rural catchment area were studied as per a detailed protocol and questionnaire. RESULTS: Of the 64 patients 44 were ischemic strokes, and 20 were hemorrhagic. Thirteen (29.55%) patients with ischemic stroke reached a center with CT scan facility within 3 hours, of whom only 7 (15.91%) were eligible to receive thrombolytic therapy as per the existing clinical and radiological criteria, but none received the therapy. Of the remaining 31 (70.45%) who arrived late, 11 (25%) had no clinical and radiological contraindications for thrombolysis, except the time factor. All the patients belonged to a low socioeconomic status and a rural background. CONCLUSION: Though a large proportion of ischemic stroke patients were eligible to receive thrombolytic therapy, the majority could not reach a center with adequate facilities within the recommended time window. More alarmingly, even for those patients who reached within the time window, no significant attempt was made to initiate thrombolysis. These data call not only for attention to improve existing patient transport facilities, but also for improving the awareness of efficacy and therapeutic window of thrombolysis in stroke, among the public as well as primary care doctors.

Clinical and radiographic risk factors for operative stroke and death in the European carotid surgery trial.

OBJECTIVES: carotid endarterectomy is associated with significant morbidity and mortality. A better understanding of the relationships between baseline characteristics and outcome may help to reduce the risks of surgery. In order to make accurate and unbiased estimates of surgical risk it is important to study cohorts of patients that were established prospectively, where independent physicians assessed outcome, and where the decision to analyse and report the results was not data-dependent. The surgical arm of the European Carotid Surgery Trial (ECST) is such a cohort. METHODS: the 30-day outcome of carotid endarterectomy was analysed in ECST surgery patients in relation to their baseline clinical and angiographic characteristics. The severity of operative strokes was compared with that of strokes that occurred in the medical group. RESULTS: 1729 patients underwent trial surgery. There were 17 deaths (1.0%, 95% CI=0.6-1.6) and 105 non-fatal major strokes (6.1%, 95% CI=5.0-7.3) within 30 days of surgery. The risk of major stroke or death was 7.1% (95% CI=5.9-8.4). The risk of disabling or fatal stroke was 3.0% (95% CI=2.1-3.8). The ratio of disabling to non-disabling operative strokes was similar to that in the medical group. Several baseline characteristics predicted the operative risk of stroke and death in univariate analyses, but only four were independent risk factors in a multiple regression analysis: presentation with cerebral TIA vs ocular ischaemic events only (HR=2.99, 95% CI=1.33-6.69, p=0.008); female sex (HR=2.04, 95% CI=1.37--3.06, p=0.001); systolic hypertension (HR=1.01 per 10 mmHg, 95% CI=1.00-1.02, p=0.03) and peripheral vascular disease (HR=2.17, 95% CI=1.17-2.89, p=0.001). CONCLUSIONS: the operative risk of stroke and death in the ECST was comparable with other prospective studies and trials in which patients were assessed postoperatively by both a physician and a surgeon. Case fatality and disability after operative stroke are similar to strokes that occur on medical treatment only. Several baseline patient characteristics predict surgical risk and it may be possible to use these characteristics to aid patient selection and surgical audit.

Acanthameba meningoencephalitis: a case report.

A 45 year old lady presented with history of recent surgery for uterovaginal prolapse and retained vaginal tampons following which she developed chronic meningitis due to acanthameba infection. Patient responded to a regimen containing albendazole. She was left with hydrocephalus as a sequelae.

Fast-wave periodic complexes in a mentally retarded child who later developed subacute sclerosing panencephalitis: a modification of a classic EEG by preexisting brain damage?

The EEG of a 12-year-old girl with stage II subacute sclerosing panencephalitis (SSPE), who had also suffered from a non-progressive mental retardation of unknown aetiology since early childhood, revealed periodic generalised stereotyped fast wave bursts synchronous with myoclonic jerks. The background activity was nearly normal. The diagnosis of SSPE was established by raised serum and measles antibody titres, raised CSF IgG, and brain biopsy. This rare type of periodic complex has only once been described in the literature, again in a mentally retarded child who had developed SSPE. We suggest a mechanism of origin of this type of periodic complex drawn from observations in these two cases, and discuss its significance.

Response to thymectomy in South Indian patients with myasthenia gravis.

AIMS: The rate of remission among patients with myasthenia gravis (MG) following thymectomy and the predictors of the outcome have revealed vast variation in studies from different geographic regions raising suspicion about the influence of ethnic factors. MATERIAL & METHODS: We retrospectively evaluated the outcome of 71 South Indian MG patients who were thymectomized between 1987 through 1993 and analyzed the relationship between clinical and histopathological features and postthymectomy outcome. RESULTS: The clinical severity of the disease did not differ between the 29 patients with and 42 patients without a thymoma. Seventynine percent of our patients responded favourably to thymectomy; without additional immunosupression therapy, 52% achieved a near-complete remission. An younger age and milder disease correlated with a good outcome. Patients with thymoma responded as favourably as those without a thymoma. CONCLUSIONS: The postthymectomy response of South Indian MG patients in general did not differ from that of Western and Oriental patients.

Neuro developmental sequelae of pyogenic meningitis in children.

97 children above one month of age with pyogenic meningitis were followed up after 6 and 12 months at the child development Center, S.A.T Hospital, Medical College, Trivandrum. Developmental quotient was obtained using Bayley scale of Infant Development, intelligence quotient using Binet-Kamath test and behavioural assessment by the Eyberg behavior inventory. The major sequelae observed were mental/developmental retardation 53.2 percent, behavioural problems 11.3 percent, focal neurological deficits 7.2 percent, epilepsy 6.2 percent and perception deafness 3.1 percent. Retardation observed in the 4-12 months age group was statistically significantly higher than the 1-3 months age group. Further, mental impairment significantly outweighed motor impairment as a sequel. Acute phase poor responders had high incidence of retardation. 37.5 percent of those who had focal deficits during acute phase, continued to have persistent deficit at 12 months follow up.

Necrotizing myelopathy--a report of two cases with review of literature.

Necrotizing myelopathy is an uncommon neurological disorder. Till 1991, only 31 cases have been described in the literature. In this report, clinical and neuropathological features in two patients with necrotizing myelopathy are described. The precise aetiological agent in first patient was undetermined, However in the second patient there was serological evidence, suggestive of Herpes simplex virus infection.

Novel antigen system for tracking epithelial cell migration in serum-free culture.

We report here a unique system for tracking normal human urothelial cell migration in serum-free culture medium (HMRI-1). The key observation was that urothelial cells deposited red blood cell surface antigen on the culture dish in a remarkable pattern. Scrutiny of this pattern showed that each migrating cell left behind antigen imprints which formed parallel tracks the width of the cell. Hence the previous migratory history of the cells was instantly mapped by simply visualizing the antigen tracks deposited by the cells on the dish. Apart from providing a simple method for tracking urothelial cells, this observation has wider implications for mechanistic studies of epithelial cell movement in general. It also highlights the complicating effects associated with the addition of serum as a traditional culture supplement, since the inclusion of serum in the HMRI-1 medium abolished the above effect by inhibiting cell migration.