Synthesis and anticancer activity of 4β-alkylamidochalcone and 4β-cinnamido linked podophyllotoxins as apoptotic inducing agents

A series of 4β-alkylamidochalcone and 4β-cinnamido linked podophyllotoxin congeners have been synthesized. All the twenty nine compounds were evaluated for anticancer activity against five human cancer cell lines (A-549, A375, MCF-7, HT-29 and ACHN). Some of the synthesized compounds showed good anticancer activity that is comparable to etoposide. The IC(50) of compounds 17a and 17f is 2.7 and 2.1?μM respectively against A-549 cancer cell line. Flow cytometric analysis showed that these two compounds arrested the cell cycle in the G2/M phase leading to caspase-3 dependent apoptotic cell death. Further, Hoechst 33258 staining and DNA fragmentation assay also suggested that 17a and 17f induced cell death by apoptosis.     

Long-term seizure outcome and its predictors in patients with recurrent seizures during the first year aftertemporal lobe resective epilepsy surgery

Purpose: The existing data on the implications of the characteristics of seizures that recur during the first year following epilepsy surgery on subsequent seizure outcome are conflicting. We investigated the impact of recurrent seizures in the first postoperative year and their attributes on long‐term seizure outcome. Methods: We studied the postoperative courses of 492 patients who had completed two or more years of follow‐up after temporal lobe resective epilepsy surgery. We used Kaplan‐Meier survival curves to define long‐term seizure outcome and assessed the predictive value of recurrent seizure characteristics on the outcome by univariate and multivariate proportional hazards regression models. Key Findings: In our patients, seizure recurrences during the first postoperative year, irrespective of the attributes of recurrent seizures (such as provoked vs. unprovoked, and timing and number of recurrences), imparted fourfold to sevenfold increased hazards for continued seizures beyond the first postoperative year. Although patients with complex partial seizures with or without secondary generalized tonic–clonic seizures (CPS/GTCS) had a sixfold increased risk, those with auras alone had only a borderline risk for seizures beyond the first postoperative year. In the multivariate model, CPS/GTCS as the predominant seizure type and three or more seizure recurrences during the first postoperative year independently predicted unfavorable long‐term seizure outcome. Significance: Our study provides valuable information that is helpful in prognosticating and counseling patients, and in making rational decisions on the withdrawal of antiepileptic drugs following surgery. Our findings enhance the general understanding of the etiopathogenesis of surgical failure.     

Primary care doctors' management behavior with respect to epilepsy in Kerala, southern India

Although a majority of persons with epilepsy in developing countries are diagnosed, treated, and followed up by primary care doctors, few efforts have been made to examine their understanding with respect to epilepsy management. Through a questionnaire survey, we gathered information about the epilepsy management behavior of 500 primary care doctors distributed across the south Indian state of Kerala. Very few of them ever had diagnosed focal seizures, and the majority of them overutilize EEGs, prescribe continuous antiepileptic drug (AED) prophylaxis for febrile convulsions, use relatively expensive AEDs often in combination and in suboptimal doses, and did not know about alternate management options for AED-resistant epilepsies. A substantial proportion of the current large treatment gap in epilepsy in developing countries could be minimized by educating the primary care physicians about the diagnosis of epileptic seizures, cost-effective AED treatment, and need-based referral for specialized care.     

Frequent seizures and polytherapy can impair quality of life in persons with epilepsy

CONTEXT: Careful evaluation of pharmacotherapy, seizure control and quality of life (QOL) are helpful in improving epilepsy care but such data are relatively meager from developing countries. AIMS: To audit pharmacotherapy, seizure control and QOL in persons with epilepsy and to identify factors associated with impaired QOL. SETTINGS AND DESIGN & MATERIALS AND METHODS: The study was carried out using a cross-sectional design in the setting of a tertiary care epilepsy center in India. Persons with epilepsy with > 12 months follow-up at this Center and aged > 16 years were eligible for enrollment. Persons with other disabilities or pregnancy were excluded. Subjects were interviewed with a standard questionnaire and an adapted version of Quality of Life in Epilepsy - 31 (QOLIE-31). Data pertaining to treatment at the time of referral to this center was extracted from medical records. STATISTICAL ANALYSIS USED: Chi-square test, analysis of variance and multiple regression analysis were carried out for statistical significance. RESULTS: One hundred and twelve patients with epilepsy (59 males, mean age 31.2+/-10.7 years) were included. Forty-seven (42%) persons had Generalized Epilepsy (GE) and 65 persons (58%) had Localization-Related Epilepsy (LRE). At entry 24 persons (21.4%) were not on treatment and 59 persons (64.8%) had frequent seizures. At last follow-up 64 persons (57.1%) were seizure-free, 83 persons (74.1%) were on monotherapy and 29 were (25.9%) on polytherapy. Cost of drug at entry was INR 2276 (monotherapy) and INR 3629 (polytherapy) (45 INR = 1 USD). At the time of last follow-up, it was 1898 and 4929 respectively. QOLIE-31 Total Score (TQOL) ranged from 22.6 to 94.4 (mean 68.0 +/- 15.8). Multiple regression analysis showed significant correlation between low TQOL score and polytherapy (P=0.002) and occurrence of one or more seizures per month (P=0.001). CONCLUSIONS: Frequent seizures and polytherapy are associated with lower QOL in persons with epilepsy.     

Mycological study of tinea versicolor

Mycological study of 100 cases of tinea versicolor was undertaken. Skin scrapings from 100 cases were subjected for culture in Sabouraud's dextrose agar, out of which 60 positive cultures (60%) were obtained.     

Outcome after corpus callosotomy in children with injurious drop attacks and severe mental retardation

Wide variability in patient selection, extent of callosal section and definition of successful outcome between studies make impact of corpus callosotomy on patients with medically refractory epilepsies difficult to interpret. Severe mental retardation is considered to be predictive of unfavorable seizure outcome after callosotomy. Very little attention has been paid on the influence of callosotomy on the psychosocial burden on the patients' families. We evaluated the seizure outcome, and parental perception about change in cognition and behavior of 17 children (median age 9.5 years, range 3.5-18 years) with severe mental retardation (IQ<30 in all, except one) and injurious drop attacks, who have completed >or=1-year postoperative follow-up after callosotomy. Nearly two-thirds of our patients had >or=90% reduction in drop attacks and generalized tonic-clonic seizures. In the one-stage total callosotomy group, 9 of 11 (82%) patients had favorable outcome, compared to 2 of the 6 (33%) in the partial callosotomy group. Absence of generalized epileptiform discharges on the 1-year postoperative EEG was significantly associated with a favorable seizure outcome. The mean duration of epilepsy prior to callosotomy tended to be shorter among patients with favorable seizure outcome. Postoperative complications were trivial and transient. Nearly three-fourths of the parents appreciated improvements in behavior and attentiveness of their children and were satisfied with the outcome. We conclude that, in children with severe mental retardation and injurious drop attacks, total callosotomy can be undertaken as a one-stage procedure with insignificant morbidity and results in highly favorable seizure outcome.     

Women with Onset of Epilepsy Prior to Marriage: Disclose or Conceal?

We inquired reasons for concealment/disclosure of the history of epilepsy during marriage negotiations and marriage outcomes of 82 consecutive women attending a tertiary referral center based epilepsy clinic in Kerala, southern India. At the time of marriage, 55% concealed and 45% disclosed the history of epilepsy. Majority of those who concealed admitted that they did so fearing breakup of marriage negotiations, and majority of those who disclosed did so to forestall the consequences after marriage of concealing. Compared to those who disclosed, the prevalence of divorce, separation and disturbed marriages were significantly higher among those who concealed. Honest prospective communication during marriage negotiations about epilepsy is important for preserving subsequent married life.     

Corpora amylacea in mesial temporal lobe epilepsy: clinico-pathological correlations

PURPOSE: To investigate the electro-clinical significance of premature accumulation of corpora amylacea (CoA) in the resected hippocampus of patients with medically refractory mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). METHODS: We compared the clinical and EEG characteristics, and post-operative seizure outcome of 373 (mean age 29.4 years, range 7-55 years) surgically treated MTLE-HS patients with (MTLE-HS-CoA(+), n=129 [34.5%]) and without (MTLE-HS-CoA(-), n=244 [65.5%]) CoA. RESULTS: Age at surgery was significantly higher and duration of epilepsy before surgery was significantly longer for MTLE-HS-CoA(+) patients compared to MTLE-HS-CoA(-) patients. Although the distribution of interictal epileptiform EEG abnormalities did not differ, type 1 ictal EEG pattern was more frequent in MTLE-HS-CoA(+) patients. Among the 21 patients with major interictal psychosis detected prior to epilepsy surgery, 19 (90.5%) belonged to MTLE-HS-CoA(+) group. Schizophrenia-like psychosis was most prevalent. The post-operative seizure-free outcome was comparable, but significantly more MTLE-HS-CoA(-) patients were free of antiepileptic drugs. CONCLUSIONS: Overall, our observations support the hypothesis that the pathological process in MTLE-HS is progressive. MTLE-HS-CoA(+) patients are predisposed to increased psychiatric morbidity. In vivo detection of hippocampal CoA accumulation in the future will help us to understand the neurobiological significance of this phenomenon.