Low-grade or minimal hepatic encephalopathy (MHE) is characterised by relatively mild neurocognitive impairments, and occurs in a substantial percentage of patients with liver disease. The presence of MHE is associated with a significant compromise of quality of life, is predictive of the onset of overt hepatic encephalopathy and is associated with a poorer prognosis for outcome. Early identification and treatment of MHE can improve quality of life and may prevent the onset of overt encephalopathy, but to date, there has been little agreement regarding the optimum method for detecting MHE. The International Society on Hepatic Encephalopathy and Nitrogen Metabolism convened a group of experts for the purpose of reviewing available data and making recommendations for a standardised approach for neuropsychological assessment of patients with liver disease who are at risk of MHE. Specific recommendations are presented, along with a proposed methodology for further refining these assessment procedures through prospective research.

SUMMARYBackground: There is paucity of data regarding occurrence of reproductive endocrine disorders in Asian women with epilepsy (WWE) on antiepileptic drug (AED) therapy. Purpose: To determine the occurrence of reproductive endocrine disorders in Indian WWE, by seizure type and the AED use. Methods: Consecutive 427 reproductive age WWE receiving various AEDs were screened for the occurrence of menstrual abnormalities, weight change, and hirsutism. Of these, 53 WWE with menstrual disturbances and/or hirsutism were further evaluated for ovarian morphology and reproductive hormonal profile. Results: Menstrual abnormalities and/or hirsutism were observed in 83 of 427 (19.4%) WWE irrespective of epileptic seizure type; of these, 50 (60.2%) received valproate, 21 (25.3%) received carbamazepine, 11 (13.3%) received phenytoin, and one (1.2%) received phenobarbitone as the primary AED. Almost half of valproate-treated women had

Piperine, the active principle of Piper longum, Piper nigrum and Zingiber officinalis, has been reported to enhance the oral bioavailability of phenytoin in human volunteers. The objective of this study was to explore the effect of a single dose of piperine in patients with uncontrolled epilepsy on the steady-state pharmacokinetics of phenytoin. Two groups of 10 patients each receiving either a 150 mg or 200 mg twice daily dose of phenytoin were selected. Twelve hours after the night dose, venous blood samples were collected at 0, 0.5, 1, 2, 4, 6, 9, 12 h after administration of phenytoin. On the next study day, piperine 20 mg was administered along with phenytoin and samples were collected similarly. The mean plasma drug concentrations at different time points and the pharmacokinetic parameters before and after piperine administration were compared by Student's t-test. Piperine increased significantly the mean plasma concentration of phenytoin at most of the time points in both dose groups. There was a significant increase in AUC((0-12h)) (p < 0.01), C(max) (p < 0.001) and K(a) (p < 0.05) whereas the changes in K(el) and t(max) were not significant. The results showed that piperine enhanced the bioavailability of phenytoin significantly, possibly by increasing the absorption.

The present study reveals that a significant number of patients with liver cirrhosis show evidence of peripheral neuropathy, which is present regardless of the etiology of cirrhosis, and is subclinical in a majority of these patients. The cause of neuropathy was probably the liver disease itself, as the incidence and severity of neuropathy in the alcohol-related cirrhosis, although higher, was not significantly different from the neuropathy in patients with non-alcohol-related cirrhosis.

Piperine, the active principle of piper species, is commonly used as a spice and adjuvant in various traditional systems of medicine. It has been known as a bioavailability-enhancer. The present study aimed at evaluating the effect of piperine on the steady-state pharmacokinetics of a single dose of carbamazepine in poorly controlled epilepsy patients on carbamazepine monotherapy. Patients (n = 10 each) receiving either 300 mg or 500 mg dose of carbamazepine twice daily were selected. After administration of carbamazepine, venous blood samples were collected at 0, 0.5, 1, 2, 4, 6, 9, 12 h. Subsequently, piperine (20 mg p.o.) was administered along with carbamazepine and samples were collected similarly. The pharmacokinetic parameters were compared by Students t-test. Piperine significantly increased the mean plasma concentrations of carbamazepine at most of the time points in both dose groups. There was a significant increase in AUC(0-12hr) (p < 0.001), average C(ss) (p < 0.001), t(1\2el) (p < 0.05) and a decrease in K(el) (p < 0.05), in both the dose groups, whereas changes in K(a) and t(1\2a) were not significant. Cmax (p < 0.01) and t(max) (p < 0.01) were increased significantly following piperine administration in the 500 mg dose group; however, these parameters were not significant in the lower dose group. Piperine could significantly enhance the oral bioavailability of carbamazepine, possibly by decreasing the elimination and/or by increasing its absorption.

Genitourinary myiasis, associated with ulcerating lesions and poor hygiene of the local site, has been infrequently reported. We report a case of 45 year-old urinary incontinent female suffering from carcinoma cervix, who presented with genitourinary myiasis. The larva was identified as of Chrysomyia bezziana Villeneuve (C. bezziana). Key words: Genitourinary myiasis, Chrysomyia bezzianaMyiasis, defined as infestation of vertebrate animals with dipterous larvae, can cause massive destruction in neglected patients accompanied by marked inflammatory reactions and secondary bacterial infections. Cutaneous myiasis is the most common form. Genitourinary involvement is rare and usually presents as pruritus and pain at the site of infection. Chrysomyia has been reported to cause myiasis in manand domestic animals in the tropics. Species implicated are C.bezziana(most common and the only known obligatory agent of myiasis), C.megacephala and C.rufifacies.2 The present case is of genitourinary myiasis caused by larvae of Old World screw-worm fly C. bezziana. Case ReportA 45 year-old female, belonging to a poor family, residing in suburban area of Delhi, reported to the radiotherapy out patient department (OPD) of a tertiary care hospital in NewDelhi, India with complaints of pruritus and gnawing pain in the periuretheral area since two days. Before visiting the clinic, she was able to manually remove a small organism from the uretheral orifice, which alleviated the pain. The patient was suffering from carcinoma cervix (grade III), since two years. Three weeeks back, she developed urinary incontinence, due to the spread of the malignancy and since then had been living in poor sanitary conditions. The organism received in the laboratory was white, measured 5mm in length and had tough but not sclerotic integument. It was mounted in chloral -gum medium and kept over a hot plate (for clearing) for a week. A subsequent examination of the urine and stool sample of the patient did not reveal any pathogen. The patient was advised to attend to the gynaecology OPD for physical examination, management of urinary incontinence and antibiotic treatment. The patient could not be followed up.

Summary:Purpose: To assess the association of long-term sodium valproate therapy with reproductive endocrine disorders in Indian women with generalized epilepsy.Methods: Clinical parameters, ovarian morphology, and serum reproductive hormone concentrations were evaluated in 30 clinically normal and eumenorrheic reproductive age women with generalized epilepsy who were newly initiated on valproate. Longitudinal evaluations were done in 25 of these women after 1 year, and in some of them after 2 and 3 years of therapy.Results: Of the 25 women who completed 1 year follow-up, we observed clinically relevant weight gain in 40%, hirsutism in 20%, menstrual abnormalities in 24%, polycystic ovaries (PCO) in 16%, polycystic ovarian syndrome (PCOS) in 20%, and a significant increase in mean serum testosterone (p = 0.046). A significant positive correlation existed between weight gain and the development of menstrual abnormalities (r = 0.66, p < 0.0001), hirsutism (r = 0.53, p = 0.006) and PCO (r = 0.51, p = 0.012). No correlation existed between weight change and serum reproductive hormonal changes. Yearly follow-up for next 2 years in some of these women revealed persistence of menstrual abnormalities, hirsutism and PCO, a significant linear increase in mean body weight, body mass index, and serum testosterone concentrations, and an increase in serum LH levels from second year onwards.Limitations: Limitations include small sample size and a high dropout rate on follow-up.Conclusions: Long-term valproate therapy in Indian women with generalized epilepsy is associated with development of hirsutism, significant weight gain, stable or progressive alterations in reproductive hormonal function, and ultimately a higher occurrence of PCOS.

Context:Parkinson's disease (PD) is associated with sleep disturbances, attributed to the neurodegenerative process and therapeutic drugs. Studies have found levodopa to increase wakefulness in some patients while increasing sleepiness in others.Aims:To confirm sleep disturbances in drug naïve PD patients and understand the impact of levodopa on their sleep.Materials and Methods:Twenty-three drug naïve PD patients and 31 age-gender matched controls were compared using the Parkinson's Disease Sleep Scale (PDSS) and Epworth Sleepiness Scale (ESS). A polysomnogram objectively compared sleep quality. Of the 23 patients, the 12 initiated on levodopa were reassessed subjectively and through polysomnography after 2 months of therapy.Statistical Analysis:Data was expressed as mean ± standard deviation, median, and range. Continuous variables were analyzed by Student's T test for normally distributed data and Mann–Whitney U test for skewed data. Discrete variables were compared by Chi Square tests (Pearson Chi square Test or Fisher's Exact Test). Wilcoxon signed ranks test was applied in the analysis of paired data pre- and post-levodopa. A P value < 0.05 was considered as statistically significant. Statistical analysis of the data was done using the Statistical Package for the Social Sciences (SPSS) version 12.Results:Drug naïve PD patients had lower PDSS scores than controls. The sleep architecture changes observed on polysomnogram were reduced NREM Stage III and REM sleep and increased sleep latency and wake after sleep onset time. Following levodopa, improved sleep efficiency with reduced sleep latency and wake after sleep onset time was noted, coupled with improved PDSS scores. However, NREM Stage III and REM sleep duration did not increase.Discussion:PD patients take longer to fall asleep and have difficulty in sleep maintenance. Sleep maintenance is affected by nocturia, REM behavioral disorder, nocturnal cramps, akinesia, and tremors, as observed in PDSS scores. Levodopa improves sleep efficiency by improving motor scores without altering sleep architecture.Conclusions:Poor sleep quality and sleep architecture changes occur secondary to the neurodegenerative process in PD patients. Though levodopa improves sleep quality by reducing rigidity and tremor, it does not reverse sleep architecture changes.