Newer anti-epileptic drugs, vitamin status and neuropathy: A cross-sectional analysis.

Science.gov (United States)

Cahill, V; McCorry, D; Soryal, I; Rajabally, Y A

Whether new antiepileptic drugs (AEDs) may result in neuropathy is unknown but possible given their effects on vitamin metabolism. This analysis aimed to determine frequency and correlates of neuropathy in subjects treated with new AEDs in relation to drug used, length of exposure and serum vitamin B12 and folate levels. We performed a cross-sectional study of 52 consecutive epileptic subjects. Presence of neuropathy was determined using the Utah Early Neuropathy Score (UENS). Exposure to anti-epileptic drugs was quantified. Serum vitamin B12 and folate levels were measured. Commonly used AEDs were levetiracetam (28/52), carbamazepine (20/52), lamotrigine (20/52), sodium valproate (10/52) and zonisamide (10/52). Eight of 52 (15.4%) patients had neuropathy. There was no association with any particular AED. Neuropathy correlated with age (P=0.038) and total exposure to AEDs (P=0.032). UENS correlated with age (P=0.001), total AED exposure (P=0.001) and serum vitamin B12L (P=0.018). Independent association of neuropathy was found with total AED exposure (P=0.032), but not age. UENS was independently associated with total exposure to AEDs (Pvitamin B12L (P=0.002), but not age. Serum vitamin B12 and folate levels were highly inter-correlated (Pvitamin B12 and folate metabolism. Although further research from controlled studies is needed and despite the presence of other possible confounding factors, monitoring for neuropathy and vitamin B12 and folate levels merits consideration in patients on long-term treatment with new AEDs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

[A modified approach to the diagnosis and therapy of epileptic seizures in the third stage of life].

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Gavranović, Muhamed; Delilović, Jasminka; Kurtović, Azra; Alibegović, Sakib; Rajić, Zeljka; Ajanović, Zakira

2003-01-01

Incidence of seizures in the elderly is nowadays greater than the one characteristic for children up to 10 years of age. Epileptic seizures are the third most common serious neurological disorder in this age group, after stroke and dementia. Optimal care for those patients, regarding to the seizures, demands some modification in diagnostic and treatment approach. Aim of this report was to point out problems in diagnostics, treatment and most common mistakes in practice. Fifty one patients were assessed, aged 65-83 years, (30 female and 21 male), with diagnosis of epilepsy and established antiepileptic treatment. All patients were re-examined, and following procedures were utilised: auto and heteroanamnesis (especially data provided by eyewitnesses), clinical examination, biochemical status, complete cardiological examination, EEG registration, serum concentrations of antiepileptic drugs, CT and MRI scan. Out of 51 patients 11 were misdiagnosed (syncope, provoked seizures, TIA). The most common form of seizures were partial seizures with or without secondary generalization (31 cases). Etiologic factors: stroke (25 cases), arteriosclerosis (7 cases), tumours (3 cases), trauma (2 cases), unknown (3 cases) cardiovascular diseases (29 casec) diabetes mellitus (20 cases), respiratory disturbance (12 cases) renal disturbances (8 cases). Only 30 patients had monotherapy from the beginning, with either carbamazepine or valproate. Rest were treated from the beginning with 2 antiepileptic drugs (phenobarbital + carbamazepine or pheytoin + phenobarbital). Adverse effects were recorded in 21 patients. I. It is crucial to distingiush unprovoked and provoked seizures during diagnostic procedures, as well as epileptic and non-epileptic attacks; 2. Principle of monotherapy is conditio sine qua non, and in treatment attention should be paid to co-morbidity, multitherapy, drug interactions, intoxication, diminished detoxication and elimination of drugs, as well as increased

Epileptic seizures precipited by eating: a case report

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Fernando Carlos Aleixo Sepulveda

1981-03-01

Full Text Available The case of one 23 year-old girl who had epileptic manifestations is reported. At first, generalized tonic seizures; afterwards, epileptic seizures precipited by eating. The electroencephalograms showed left temporal lobe disfunctions. Different types of drugs were used with no sucess. The best results were obtained by association of sodium valproate, clonazepan and phenobarbital. Comments are made about clinic and etiopathogenesis, believing the authors in the hipothesis of nervous structures chronic hiperactivity. To Walker8 the hiperactivity was reached by hormones production under neural control of specific cerebral centers. The continuous bombardment of epileptic discharges to hypothalamic centers is the probably responsible by epileptic seizures precipited by eating.

Determination of Four Anti-epileptic Drugs in Plasma Using Ultra Performance Liquid Chromatography with Mass Detection Technique.

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Hassib, Sonia T; Hashem, Hanaa M A; Mahrouse, Marianne A; Mostafa, Eman A

2018-04-10

Status epilepticus (SE) is considered the second most frequent neurologic emergency. Its therapeutic management is performed using sequential anti-epileptic drug regimens. Diazepam (DIA), midazolam (MID), phenytoin (PHT) and phenobarbital (PB) are four drugs of different classes used sequentially in the management of SE. A sensitive, selective, accurate and precise method was developed and validated for simultaneous determination of the four anti-epileptic drugs in human plasma. Their separation and quantification were achieved using ultra performance liquid chromatography (UPLC) with mass detection using carbamazepine as internal standard (IS). For the first three drugs and IS, UPLC-MS/MS with electrospray ionization working in multiple reaction monitoring mode was used at the following transitions: m/z 285→193 for DIA, m/z 326→291 for MID, m/z 253→182 for PHT and m/z 237→194, 237→192 for IS. For the fourth drug (PB), molecular ion peak of PB [M+H] + at m/z 233 was used for its quantitation. The method was linear over concentration ranges of 5-500 ng/ml for DIA and MID and 0.25-20 μg/ml for PHT and PB, respectively. Bio-analytical validation of the developed method was carried out according to European Medicines Agency guidelines. The developed method can be applied for routine drug analysis, therapeutic drug monitoring and bioequivalence studies. This article is protected by copyright. All rights reserved.

Immune-mediated steroid-responsive epileptic spasms and epileptic encephalopathy associated with VGKC-complex antibodies.

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Suleiman, Jehan; Brenner, Tanja; Gill, Deepak; Troedson, Christopher; Sinclair, Adriane J; Brilot, Fabienne; Vincent, Angela; Lang, Bethan; Dale, Russell C

2011-11-01

Autoantibodies that bind to voltage-gated potassium-channel complex proteins (VGKC-complex antibodies) occur frequently in adults with limbic encephalitis presenting with cognitive impairment and seizures. Recently, VGKC-complex antibodies have been described in a few children with limbic encephalitis, and children with unexplained encephalitis presenting with status epilepticus. We report a case of infantile-onset epileptic spasms and developmental delay compatible with epileptic encephalopathy. Our patient was a female infant, aged 4 months at presentation. She had evidence of immune activation in the central nervous system with elevated cerebrospinal fluid neopterin and mirrored oligoclonal bands, which prompted testing for autoantibodies. VGKC-complex antibodies were elevated (201 pmol/L, normalVGKC-complex antibodies might represent a marker of immune therapy responsiveness in a subgroup of patients with infantile epileptic encephalopathy. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

The evaluation of 25-hydroxy vitamin D, calcium, phosphate and alkaline phosphatase levels in epileptic children under antiepileptic medication

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Keyhani doost Z

2011-01-01

Full Text Available "n 800x600 Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 st1":*{behavior:url(#ieooui } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman","serif";} Background: Epilepsy is a common disease in the pediatric neurology. There are frequent anti-epileptic drugs which are used in management of epilepsy. Anti-epileptic drugs may have some complications on bone and vitamin-D metabolism. In this study we aimed to evaluate vitamin-D metabolism in epileptic children."n"nMethods: The study was a prospective and cross sectional one. A total 89 epileptic children who were taking anti-epileptic drugs for longer than six months with no underlying disorder in Imam Khomeini and Bahrami Hospitals in Tehran, Iran were enrolled in our study"n"nResults: Forty nine boys and 40 girls were enrolled in this study; mean age of the patients was 7.8±2.1 years. Mean duration of anti-epileptic drug therapy was 2.3 years (SD=0.4, 70 of patients were under monotherapy and 19 were under polytherapy. None of the patients had signs of rickets. Serum calcium and phosphor levels were within normal ranges. Serum alkaline phosphates levels were increased more than two times in 43%. 42% had vitamin-D deficiency (25-OH Vit D<10 ng/ml and another 33% had vitamin-D insufficiency (10<25-oh Vit D<20 ng/ml. 29 patients (32% were taking prophylactic supplemental Vit D (200-400 IU/day. There was significant difference between patients taking supplemental vitamin-D as prophylaxis and patients who did not (p=0.04. There was no significant difference in vitamin-D levels between patients according to age, gender or different drugs."n"nConclusion: Periodic

Epileptic peri-ictal psychosis, a reversible cause of psychosis.

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González Mingot, C; Gil Villar, M P; Calvo Medel, D; Corbalán Sevilla, T; Martínez Martínez, L; Iñiguez Martínez, C; Santos Lasaosa, S; Mauri Llerda, J A

2013-03-01

Epileptic psychoses are categorised as peri-ictal and interictal according to their relationship with the occurrence of seizures. There is a close temporal relationship between peri-ictal psychosis and seizures, and psychosis may present before (preictal), during (ictal) or after seizures (postictal). Epileptic psychoses usually have acute initial and final phases, with a short symptom duration and complete remission with a risk of recurrence. There is no temporal relationship between interictal or chronic psychosis and epileptic seizures. Another type of epileptic psychosis is related to the response to epilepsy treatment: epileptic psychosis caused by the phenomenon of forced normalisation (alternative psychosis), which includes epileptic psychosis secondary to epilepsy surgery. Although combination treatment with antiepileptic and neuroleptic drugs is now widely used to manage this condition, there are no standard treatment guidelines for epileptic psychosis. We present 5 cases of peri-ictal epileptic psychosis in which we observed an excellent response to treatment with levetiracetam. Good control was achieved over both seizures and psychotic episodes. Levetiracetam was used in association with neuroleptic drugs with no adverse effects, and our patients did not require high doses of the latter. Categorising psychotic states associated with epilepsy according to their temporal relationship with seizures is clinically and prognostically useful because it provides important information regarding disease treatment and progression. The treatment of peri-ictal or acute mental disorders is based on epileptic seizure control, while the treatment of interictal or chronic disorders has more in common with managing disorders which are purely psychiatric in origin. In addition to improving the patient's quality of life and reducing disability, achieving strict control over seizures may also prevent the development of interictal psychosis. For this reason, we believe that

Assessing quantitative EEG spectrograms to identify non-epileptic events.

Science.gov (United States)

Goenka, Ajay; Boro, Alexis; Yozawitz, Elissa

2017-09-01

To evaluate the sensitivity and specificity of quantitative EEG (QEEG) spectrograms in order to distinguish epileptic from non-epileptic events. Seventeen patients with paroxysmal non-epileptic events, captured during EEG monitoring, were retrospectively assessed using QEEG spectrograms. These patients were compared to a control group of 13 consecutive patients (ages 25-60 years) with epileptic seizures of similar semiology. Assessment of raw EEG was employed as the gold standard against which epileptic and non-epileptic events were validated. QEEG spectrograms, available using Persyst 12 EEG system integration software, were each assessed with respect to their usefulness to distinguish epileptic from non-epileptic seizures. The given spectrogram was interpreted as indicating a seizure if, at the time of the clinically identified event, it showed a visually significant change from baseline. Eighty-two clinically identified paroxysmal events were analysed (46 non-epileptic and 36 epileptic). The "seizure detector trend analysis" spectrogram correctly classified 33/46 (71%) non-epileptic events (no seizure indicated during a clinically identified event) vs. 29/36 (81%) epileptic seizures (seizure indicated during a clinically identified event) (p=0.013). Similarly, "rhythmicity spectrogram", FFT spectrogram, "asymmetry relative spectrogram", and integrated-amplitude EEG spectrogram detected 28/46 (61%), 30/46 (65%), 22/46 (48%) and 27/46 (59%) non-epileptic events vs. 27/36 (75%), 25/36 (69%), 25/36 (69%) and 27/36 (75%) epileptic events, respectively. High sensitivities and specificities for QEEG seizure detection analyses suggest that QEEG may have a role at the bedside to facilitate early differentiation between epileptic seizures and non-epileptic events in order to avoid unnecessary administration of antiepileptic drugs and possible iatrogenic consequences.

Pharmacological response of systemically derived focal epileptic lesions

Energy Technology Data Exchange (ETDEWEB)

Remler, M.P.; Sigvardt, K.; Marcussen, W.H.

1986-11-01

Focal epileptic lesions were made in rats by systemic focal epileptogenesis. In this method, a focal lesion of the blood-brain barrier (BBB) is produced by focal alpha irradiation followed by repeated systemic injection of a convulsant drug that cannot cross the normal BBB, resulting in a chronic epileptic focus. Changes in the spike frequency of these foci in response to various drugs was recorded. The controls, saline and chlorpromazine, produced no change. Phenytoin, phenobarbital, chlordiazepoxide, and valproic acid produced the expected decrease in spike frequency. Pentobarbital and diazepam produced a paradoxical increase in spike frequency.

Knowledge and attitude of Iranian community pharmacists about the pharmaceutical care for epileptic females

International Nuclear Information System (INIS)

Sabzghabaee, A.M.; Zolfaghari, B.; Ebrahimabadi, M.H.

2012-01-01

This study was designed to evaluate the knowledge and attitude of a cohort of Iranian community pharmacists about the pharmaceutical care indexes and drug therapy in female epileptic patients. Methodology: This cross-sectional study was conducted in Iran (2011) and one hundred and twenty two community pharmacists were randomly selected using clustering method for sampling. A self-administered questionnaire which was originally made by a clinical pharmacy focus group was used. This questionnaire had 10 true/false questions for knowledge assessing (Spearman-Brown coefficient, 0.65) and 19 attitude statements (with Likert scale) about the intention of pharmacists for providing pharmaceutical care for epileptic females (Croanbach's alpha, 0.802). Face and content validity for both parts of the questionnaire were performed before the study. Results: There was a significant inverse relationship between pharmacists' knowledge on pharmaceutical care for epileptic females and the time elapsed from their graduation date. Considering the minimum passing score of 5, 85% of pharmacists did not have enough knowledge. The range of pharmacists' attitude scores was 35 to 64 and its mean was 46.09. Regarding the minimum passing score of 45, 63.3% of pharmacists had positive attitude to AEDs in epileptic females. Conclusion: It seems that the pharmaceutical care for epileptic females is a missing part of Pharmacy education. It is highly recommended to pay special attention to this topic in continuing education programs for Iranian pharmacists. (author)

The effect of antiepileptic drugs on cognitive functions

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A. S. Kotov

2013-01-01

Full Text Available Impaired cognitive function is a common problem in epileptic patients. The exact cause of cognitive impairment in case of epilepsy has not been explored fully, but there is no doubt that a role in this is played by three factors: the disease underlying epilepsy; epileptic seizures proper; and negative side effects of antiepileptic drugs. Their cognitive effects are one of the major problems affecting the tolerance of therapy. The review considers the effects of phenobarbital, phenytoin, carbamazepine, valproates, oxcarbazepine, topiramate, lamotrigine, and levetiracetam in terms of their action on the cognitive function of healthy volunteers and epileptic patients.

Topiramate-induced paresthesia is more frequently reported by migraine than epileptic patients.

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Sedighi, Behnaz; Shafiei, Kaveh; Azizpour, Iman

2016-04-01

Topiramate is an approved and effective drug in migraine prophylaxis. Paresthesia is the most commonly reported side effect. The primary objective of this study was to compare the frequency of topiramate-induced paresthesia in migraine headache to epileptic patients. Patients with migraine without aura and epilepsy were enrolled in this observational study. All cases were interviewed by telephone about their history of paresthesia. Confounding factors were controlled through logistic regression. The odds ratio of developing topiramate-induced paresthesia in migraine compared to epilepsy patients was 3.4. Three factors were independent contributors to developing topiramate-induced paresthesia: female sex (odds ratio 2.1), topiramate dosage (odds ratio 0.3) and duration of therapy. Our findings indicate an independent association between migraine and development of paresthesia. Migraineurs were more likely than epileptic patients to report paresthesia as topiramate adverse effects. Female sex, treatment duration and topiramate dosage contribute significantly to subsequent development of paresthesia.

Development Enamel Defects in Children Prenatally Exposed to Anti-Epileptic Drugs

DEFF Research Database (Denmark)

Jacobsen, Pernille Endrup; Henriksen, Tine Brink; Haubek, Dorte

2013-01-01

Objective Some anti-epileptic drugs (AED) have well-known teratogenic effects. The aim of the present study was to elucidate the effect of prenatal exposure to AED and the risk of enamel defects in the primary and permanent dentition. Methods A total of 38 exposed and 129 non-exposed children, 6......–10 years of age, were recruited from the Aarhus Birth Cohort and the Department of Neurology, Viborg Regional Hospital, Denmark. Medication during pregnancy was confirmed by the Danish Prescription Database. All children had their teeth examined and outcomes in terms of enamel opacities and enamel...... hypoplasia were recorded. Results Children prenatally exposed to AED have an increased prevalence of enamel hypoplasia (11% vs. 4%, odds ratio (OR) = 3.6 [95% confidence interval (CI): 0.9 to 15.4]), diffuse opacities (18% vs. 7%, OR = 3.0; [95% CI: 1.0 to 8.7, p3) white opacities (18...

Focal epileptic seizures with secondary generalization in cortical atrophy and gliosis dysplasia in the left temporal lobe and hemimegalencephaly in the left occipital lobe

International Nuclear Information System (INIS)

Manchev, I.; Mancheva-Ganeva, V.; Manolova, T.; Manchev, L.

2016-01-01

It is a case of an eight-year-old patient with cortical dysplasia and gliosis in the left temporal lobe clinically manifested with focal epileptic seizures with secondary generalization. Signs of mental retardation and a number of somatic complications - diabetes, etc., were found. The complex therapy with anticonvulsant medications, immunovenin, plasmaphoresis and anti-diabetic drugs was partially effective

Thirty Years of Orphan Drug Legislation and the Development of Drugs to Treat Rare Seizure Conditions: A Cross Sectional Analysis

OpenAIRE

D?ring, Jan Henje; Lampert, Anette; Hoffmann, Georg F.; Ries, Markus

2016-01-01

Background Epilepsy is a serious chronic health condition with a high morbidity impairing the life of patients and afflicted families. Many epileptic conditions, especially those affecting children, are rare disorders generating an urgent medical need for more efficacious therapy options. Therefore, we assessed the output of the US and European orphan drug legislations. Methods Quantitative analysis of the FDA and EMA databases for orphan drug designations according to STrengthening the Repor...

Video electroencephalography monitoring differentiates between epileptic and non-epileptic seizures

DEFF Research Database (Denmark)

Nørmark, Mette Borch; Erdal, Jesper; Kjær, Troels Wesenberg

2011-01-01

Epilepsy is often misdiagnosed and approximately one in every four patients diagnosed with refractory epilepsy does not have epilepsy, but instead non-epileptic seizures. Video electroencephalography monitoring (VEM) is the gold standard for differentiation between epileptic and non...

Effects of anticonvulsants and inactivity on bone disease in epileptics

Science.gov (United States)

Murchison, Lilian E.; Bewsher, P. D.; Chesters, Marion; Gilbert, J.; Catto, G.; Law, Elizabeth; McKay, E.; Ross, H. S.

1975-01-01

No significant biochemical or radiological features of vitamin D deficiency were found in groups of juvenile and adult epileptics and control groups of non-epileptic patients in hospitals for the mentally retarded. There was evidence of hepatic enzyme induction in patients on anticonvulsants, in that urinary D-glucaric acid concentration and excretion were raised. No effect was found of prolonged anticonvulsant therapy on bone densitometry, but in children immobility was closely associated with decreased bone density. The evidence suggests that disuse osteoporosis is the major bone disease in these mentally retarded children. PMID:1161672

Epileptic Seizure Prediction Using a New Similarity Index for Chaotic Signals

Science.gov (United States)

Niknazar, Hamid; Nasrabadi, Ali Motie

Epileptic seizures are generated by abnormal activity of neurons. The prediction of epileptic seizures is an important issue in the field of neurology, since it may improve the quality of life of patients suffering from drug resistant epilepsy. In this study a new similarity index based on symbolic dynamic techniques which can be used for extracting behavior of chaotic time series is presented. Using Freiburg EEG dataset, it is found that the method is able to detect the behavioral changes of the neural activity prior to epileptic seizures, so it can be used for prediction of epileptic seizure. A sensitivity of 63.75% with 0.33 false positive rate (FPR) in all 21 patients and sensitivity of 96.66% with 0.33 FPR in eight patients were achieved using the proposed method. Moreover, the method was evaluated by applying on Logistic and Tent map with different parameters to demonstrate its robustness and ability in determining similarity between two time series with the same chaotic characterization.

Transient epileptic amnesia: clinical report of a cohort of patients.

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Lapenta, Leonardo; Brunetti, Valerio; Losurdo, Anna; Testani, Elisa; Giannantoni, Nadia Mariagrazia; Quaranta, Davide; Di Lazzaro, Vincenzo; Della Marca, Giacomo

2014-07-01

Transient epileptic amnesia is a seizure disorder, usually with onset in the middle-elderly and good response to low dosages of antiepileptic drugs. We describe the clinical, electroencephalography (EEG), and neuroimaging features of 11 patients with a temporal lobe epilepsy characterized by amnesic seizures as the sole or the main symptom. We outline the relevance of a detailed clinical history to recognize amnesic seizures and to avoid the more frequent misdiagnoses. Moreover, the response to monotherapy was usually good, although the epileptic disorder was symptomatic of acquired lesions in the majority of patients.

Differentiating epileptic from non-epileptic high frequency intracerebral EEG signals with measures of wavelet entropy.

Science.gov (United States)

Mooij, Anne H; Frauscher, Birgit; Amiri, Mina; Otte, Willem M; Gotman, Jean

2016-12-01

To assess whether there is a difference in the background activity in the ripple band (80-200Hz) between epileptic and non-epileptic channels, and to assess whether this difference is sufficient for their reliable separation. We calculated mean and standard deviation of wavelet entropy in 303 non-epileptic and 334 epileptic channels from 50 patients with intracerebral depth electrodes and used these measures as predictors in a multivariable logistic regression model. We assessed sensitivity, positive predictive value (PPV) and negative predictive value (NPV) based on a probability threshold corresponding to 90% specificity. The probability of a channel being epileptic increased with higher mean (p=0.004) and particularly with higher standard deviation (pentropy is likely to be epileptic; with a threshold corresponding to 90% specificity our model can reliably select a subset of epileptic channels. Most studies have concentrated on brief ripple events. We showed that background activity in the ripple band also has some ability to discriminate epileptic channels. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

The Investigation of Insulin Resistance in Two Groups of Epileptic Patients Treated with Sodium Valproate and Carbamazepine

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Mohammad Reza Najafi

2017-01-01

Full Text Available Background: Valproic acid (VPA is a widely used broad-spectrum antiepileptic drug for therapy of generalized and focal epilepsies. Cross-sectional studies have suggested that valproate treatment may be associated with hyperinsulinemia. We decided to investigate hyperinsulinemia as a health-threatening side effect of VPA in Iranian epileptic patients. Materials and Methods: Body mass index (BMI, lipid profile, fasting serum insulin, fasting blood glucose (FBS, and homeostatic model assessment-insulin resistance (HOMA-IR were measured in 30 VPA-treated epileptic patients and 30 controls (CBZ-treated. The Chi-square test, t-test, and Pearson correlation test were used. Results: BMI was higher in VPA group than in control group (25.7 ± 3.5 > 21.7 ± 4.1 (0.000 0.05. Conclusion: Despite the majority of previous studies that are against VPA and according to our study, VPA could be prescribed safely and it may not cause IR and its complications.

Automated differentiation between epileptic and non-epileptic convulsive seizures

DEFF Research Database (Denmark)

Beniczky, Sándor; Conradsen, Isa; Moldovan, Mihai

2015-01-01

Our objective was the clinical validation of an automated algorithm based on surface electromyography (EMG) for differentiation between convulsive epileptic and psychogenic nonepileptic seizures (PNESs). Forty-four consecutive episodes with convulsive events were automatically analyzed with the a......%) and 18 PNESs (95%). The overall diagnostic accuracy was 95%. This algorithm is useful for distinguishing between epileptic and psychogenic convulsive seizures....

Ketogenic diet efficacy in the treatment of intractable epileptic spasms.

Science.gov (United States)

Kayyali, Husam R; Gustafson, Megan; Myers, Tara; Thompson, Lindsey; Williams, Michelle; Abdelmoity, Ahmad

2014-03-01

To determine the efficacy of the ketogenic diet in controlling epileptic spasms after failing traditional antiepileptic medication therapy. This is a prospective, case-based study of all infants with epileptic spasms who were referred for treatment with the ketogenic diet at our hospital between 2009 and 2012. All subjects continued to have epileptic spasms with evidence of hypsarrhythmia or severe epileptic encephalopathy on electroencephalography despite appropriate medication treatments. The diet efficacy was assessed through clinic visits, phone communications, and electroencephalography. Quality of life improvement was charted based on the caregiver's perspective. Twenty infants (15 males) were included in the study. The mean age at seizure onset was 4.5 months. Age at ketogenic diet initiation was 0.3 to 2.9 years (mean 1.20, standard deviation 0.78). Fifteen patients had epileptic spasms of unknown etiology; three had perinatal hypoxic ischemic encephalopathy, one had lissencephaly, and one had STXBP1 mutation. Fifteen infants failed to respond to adrenocorticotropin hormone and/or vigabatrin before going on the ketogenic diet. Three months after starting the diet, >50% seizure reduction was achieved in 70% of patients (95% CI 48-86). These results were maintained at 6- and 12-month intervals. All eight of the patients followed for 24 months had >50% seizure reduction (95% CI 63-100). At least 90% seizure reduction was reported in 20% of patients at 3 months (95% CI 7-42), 22% (95% CI 8-46) at 6 months, and 35% (95% CI 17-59) at 12 months. The majority of patients (63%) achieved improvement of their spasms within 1 month after starting the diet. Sixty percent of patients had electroencephalographic improvement. All caregivers reported improvement of the quality of life at the 3-month visit (95% confidence interval 81-100). This ratio was 94% at 6 months (95% CI 72-99) and 82% at 12 months (95% CI 58-95). The ketogenic diet is a safe and potentially

Fertility rate oF epileptic women at Kenyatta national Hospital

African Journals Online (AJOL)

2008-07-07

Jul 7, 2008 ... multifaceted, and both epilepsy and antiepileptic drug (aeDs) use may alter fertility and pregnancy ... Conclusion: Fertility rate in epileptic women is decreased by two thirds ..... The effect of this bias on our primary aim was.

[Peptidergic nootropic therapy in cerebral palsy associated with epilepsy].

Science.gov (United States)

Kholin, A A; Zavadenko, N N; Il Ina, E S; Kolpakchi, L M; Fedonyuk, I D; Bembeeva, R C; Esipova, E S

To assess the efficacy and safety of сortexin in the treatment of children with cerebral palsy (CP) combined with epilepsy. Eighty-four patients (55 boys and 29 girls), aged from 1 to 11 years, with CP combined with epilepsy received cortexin together with antiepileptic drugs (AEDs). Cortexin was administered in doses of 5-10 mg depending on the patient's age and body weight intramuscularly during hospitalization. Cortexin as add-on to AEDs reduced for more than two times the number of seizures, along with improvement of motor function, in 31 (36.9%) patients. The improvement of motor function, but without a significant decrease in epileptic seizures, was achieved in 15 (17.8%) of the patients. Reduction of epileptic seizures frequency (>2 times), but without a significant effect on motor function, was observed in 14 cases (16.7%). Twenty-three patients (27.4%) did not respond the therapy. The aggravation of epileptic seizures during cortexin therapy was observed in only 1 girl with West syndrome (1.2%), and this was significantly lower than the probability of seizures aggravation on AED. Polypeptide nootropic medication cortexin demonstrated efficacy and safety as adjunctive therapy in children with CP combined with epilepsy.

Exfoliative Dermatitis Due To Carbamazepine In An Epileptic Patient

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Ghosh Sadhan Kr

1995-01-01

Full Text Available A young epileptic girl of 17 years who was being treated with carbamazepine suddenly developed exanthematous skin eruption all over the body resulting in exfoliative dermatitis within 2 days of onset. The drug was withdrawn and the patient responded well with symptomatic treatment.

Changes of cortical epileptic afterdischarges under the influence of convulsant drugs

Czech Academy of Sciences Publication Activity Database

Koryntová, Hana; Kubová, Hana; Tutka, P.; Mareš, Pavel

2002-01-01

Roč. 58, č. 1 (2002), s. 49-54 ISSN 0361-9230 R&D Projects: GA ČR GA309/00/1643 Institutional research plan: CEZ:AV0Z5011922 Keywords : epileptic afterdischarges * cerebral cortex * rat Subject RIV: FH - Neurology Impact factor: 2.283, year: 2002

Reports on Polysomnograph Combined with Long-term Video Electroencephalogram for Monitoring Nocturnal Sleep-breath Events in 82 Epileptic Patients

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Hongliang Li

2013-06-01

Full Text Available Objective: To investigate the effects of epileptic discharges in sleep of epileptic patients on sleepbreath events. Methods: Polysomnograph (PSG and long-term video electroencephalogram (LTVEEG were used to monitor 82 adult epileptic patients. The condition of paroxysmal events in nocturnal sleep was analyzed, and the epileptiform discharge and effects of antiepileptic drugs were explored. Results: In epileptic group, latency to persistent sleep (LPS and REM sleep latency increased, the proportion of light sleep increased while that of deep sleep decreased, sleep efficiency reduced, nocturnal arousal times increased and apnea hyponea indexes (AHI improved, which demonstrated significant differences by comparison to control group. Periodic leg movements (PLM had no conspicuous differences compared with control group. There were no specific effects of epileptiform discharge and antiepileptic drugs on AHI and PLM indexes. Conclusion: Epileptic patients have sleep structure disorders and sleep-disordered breathing, and arousal, respiratory and leg movement events influence mutually. Synchronous detection of PSG combined with LTVEEG is in favor of comprehensively analyzing the relationship between sleep structures and epilepsy-breath events.

Computed tomography of epileptic children

International Nuclear Information System (INIS)

Kurihara, Mana; Yamashita, Sumimasa; Miyake, Shota; Yamada, Michiko; Iwamoto, Hiroko

1986-01-01

The aim of this study was to analyze the changes seen on cranial computed tomography (CT) of epileptic children, especially in the area of the temporal horn. The subjects were 242 epileptic children excluding those with encephalitis, brain tumor, neurocutaneous syndromes, degenerative disease, hydrocephalus etc. The control subjects were 195 children without any neurological disease and symptoms. CT scan were taken with a TCT-60A whole body scanner, and 14 check points were evaluated excluding the temporal horn. 195 epileptic children (N-group) and all control children were normal at 14 check points. Next, the areas of the temporal horns and adjoining hemispheres of the epileptic children (N-group) and control children were examined with Muto-Tablet-Desitizer. The temporal horn ratio ((area of temporal horn/area of ipsilateral hemisphere) x 100) was greater in younger children of the control group, and it was higher in epileptic than in control children. Enlargement of the temporal horn was seen in 1 % of the controls and in 35 % of the 125 epileptic children with normal measurements at 14 points on CT scans (p < 0.01). The frequency of enlargement of temporal horns was not variable among different epileptic types. In the epileptic children with normal CT scans except for enlargement of temporal horns behavioral disturbances were 6 boys and 5 had enlarged temporal horns (bilateral 1 case, left side 1 case, right side 3 cases). (author)

Biomarkers of epileptic seizures and epilepsy

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Bogdan Lorber

2013-07-01

Full Text Available The purpose of this article is to review biological markers, their importance and usefulness in the diagnosis of epileptic seizure or epilepsy. Assessed are also their prognostic value, their use in the evaluation of antiepileptic therapy effect and some other useful properties. The article reviews prolactin, neuron specific enolase, S–100 protein, creatin kinase, laminin, matrix metalloproteinase, nesfatin–1, ghrelin, obestatin and chromogranin A. The authors stress the need for further research studies in this area.

Domoic Acid Epileptic Disease

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John S. Ramsdell

2014-03-01

Full Text Available Domoic acid epileptic disease is characterized by spontaneous recurrent seizures weeks to months after domoic acid exposure. The potential for this disease was first recognized in a human case study of temporal lobe epilepsy after the 1987 amnesic shellfish-poisoning event in Quebec, and was characterized as a chronic epileptic syndrome in California sea lions through investigation of a series of domoic acid poisoning cases between 1998 and 2006. The sea lion study provided a breadth of insight into clinical presentations, unusual behaviors, brain pathology, and epidemiology. A rat model that replicates key observations of the chronic epileptic syndrome in sea lions has been applied to identify the progression of the epileptic disease state, its relationship to behavioral manifestations, and to define the neural systems involved in these behavioral disorders. Here, we present the concept of domoic acid epileptic disease as a delayed manifestation of domoic acid poisoning and review the state of knowledge for this disease state in affected humans and sea lions. We discuss causative mechanisms and neural underpinnings of disease maturation revealed by the rat model to present the concept for olfactory origin of an epileptic disease; triggered in dendodendritic synapases of the olfactory bulb and maturing in the olfactory cortex. We conclude with updated information on populations at risk, medical diagnosis, treatment, and prognosis.

The ketogenic diet can be used successfully in combination with corticosteroids for epileptic encephalopathies.

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Ville, Dorothée; Chiron, Catherine; Laschet, Jacques; Dulac, Olivier

2015-07-01

Hormonal therapy or ketogenic diet often permits overcoming the challenging periods of many epileptic encephalopathies (West and Lennox-Gastaut syndromes and encephalopathy with continuous spike-waves in slow sleep), but relapse affects over 20% of patients. We report here a monocenter pilot series of 42 consecutive patients in whom we combined oral steroids with the ketogenic diet for corticosteroid-resistant or -dependent epileptic encephalopathy. We retrospectively evaluated the effect on seizure frequency, interictal spike activity, neuropsychological course, and steroid treatment course. Twenty-three patients had West syndrome (WS), 13 had encephalopathy with continuous spike-waves in slow sleep (CSWS), and six others had miscellaneous epileptic encephalopathies. All patients succeeded to reach 0.8 to 1.6g/l ketone bodies in the urine following the usual KD regimen. For at least 6 months, 14/42 responded to the addition of the ketogenic diet: 4/23 with WS, 8/13 with CSWS, and 2/6 with miscellaneous epileptic encephalopathies. The addition of the KD allowed withdrawing steroids in all responders. Among them, 10/15 had been patients with steroid-dependent epileptic encephalopathy and 4/27 patients with steroid-resistant epileptic encephalopathy. Therefore, the ketogenic diet can be used successfully in combination with corticosteroids for epileptic encephalopathies. Patients presenting with steroid-dependent CSWS seem to be the best candidates. Copyright © 2015 Elsevier Inc. All rights reserved.

The Anticonvulsant Effects of Ketogenic Diet on Epileptic Seizures and Potential Mechanisms.

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Zhang, Yifan; Xu, Jingwei; Zhang, Kun; Yang, Wei; Li, Bingjin

2018-01-01

Epilepsy is a syndrome of brain dysfunction induced by the aberrant excitability of certain neurons. Despite advances in surgical technique and anti-epileptic drug in recent years, recurrent epileptic seizures remain intractable and lead to a serious morbidity in the world. The ketogenic diet refers to a high-fat, low-carbohydrate and adequate-protein diet. Currently, its beneficial effects on epileptic seizure reduction have been well established. However, the detailed mechanisms underlying the anti-epileptic effects of ketogenic diet are still poorly understood. In this article, the possible roles of ketogenic diet on epilepsy were discussed. Data was obtained from the websites including Web of Science, Medline, Pubmed, Scopus, based on these keywords: "Ketogenic diet" and "epilepsy". As shown in both clinical and basic studies, the therapeutic effects of ketogenic diet might involve neuronal metabolism, neurotransmitter function, neuronal membrane potential and neuron protection against ROS. In this review, we systematically reviewed the effects and possible mechanisms of ketogenic diet on epilepsy, which may optimize the therapeutic strategies against epilepsy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Nonlinear mixed effects modelling approach in investigating phenobarbital pharmacokinetic interactions in epileptic patients.

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Vučićević, Katarina; Jovanović, Marija; Golubović, Bojana; Kovačević, Sandra Vezmar; Miljković, Branislava; Martinović, Žarko; Prostran, Milica

2015-02-01

The present study aimed to establish population pharmacokinetic model for phenobarbital (PB), examining and quantifying the magnitude of PB interactions with other antiepileptic drugs concomitantly used and to demonstrate its use for individualization of PB dosing regimen in adult epileptic patients. In total 205 PB concentrations were obtained during routine clinical monitoring of 136 adult epilepsy patients. PB steady state concentrations were measured by homogeneous enzyme immunoassay. Nonlinear mixed effects modelling (NONMEM) was applied for data analyses and evaluation of the final model. According to the final population model, significant determinant of apparent PB clearance (CL/F) was daily dose of concomitantly given valproic acid (VPA). Typical value of PB CL/F for final model was estimated at 0.314 l/h. Based on the final model, co-therapy with usual VPA dose of 1000 mg/day, resulted in PB CL/F average decrease of about 25 %, while 2000 mg/day leads to an average 50 % decrease in PB CL/F. Developed population PB model may be used in estimating individual CL/F for adult epileptic patients and could be applied for individualizing dosing regimen taking into account dose-dependent effect of concomitantly given VPA.

Importance of competing risks in the analysis of anti-epileptic drug failure

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Sander Josemir W

2007-03-01

Full Text Available Abstract Background Retention time (time to treatment failure is a commonly used outcome in antiepileptic drug (AED studies. Methods Two datasets are used to demonstrate the issues in a competing risks analysis of AEDs. First, data collection and follow-up considerations are discussed with reference to information from 15 monotherapy trials. Recommendations for improved data collection and cumulative incidence analysis are then illustrated using the SANAD trial dataset. The results are compared to the more common approach using standard survival analysis methods. Results A non-significant difference in overall treatment failure time between gabapentin and topiramate (logrank test statistic = 0.01, 1 degree of freedom, p-value = 0.91 masked highly significant differences in opposite directions with gabapentin resulting in fewer withdrawals due to side effects (Gray's test statistic = 11.60, 1 degree of freedom, p = 0.0007 but more due to poor seizure control (Gray's test statistic = 14.47, 1 degree of freedom, p-value = 0.0001. The significant difference in overall treatment failure time between lamotrigine and carbamazepine (logrank test statistic = 5.6, 1 degree of freedom, p-value = 0.018 was due entirely to a significant benefit of lamotrigine in terms of side effects (Gray's test statistic = 10.27, 1 degree of freedom, p = 0.001. Conclusion Treatment failure time can be measured reliably but care is needed to collect sufficient information on reasons for drug withdrawal to allow a competing risks analysis. Important differences between the profiles of AEDs may be missed unless appropriate statistical methods are used to fully investigate treatment failure time. Cumulative incidence analysis allows comparison of the probability of failure between two AEDs and is likely to be a more powerful approach than logrank analysis for most comparisons of standard and new anti-epileptic drugs.

Drug reaction with eosinophilia and systemic symptoms syndrome in a patient taking phenytoin and levetiracetam: a case report

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Hall David Jeffrey

2013-01-01

Full Text Available Abstract Introduction Drug reaction with eosinophilia and systemic symptoms syndrome is a potentially life-threatening hypersensitivity reaction with rash, fever, and internal organ involvement, often hepatitis, occurring most commonly two to eight weeks after initiation of a medication. The present case is an example of severe and potentially life-threatening hepatitis as a manifestation of drug reaction with eosinophilia and systemic symptoms syndrome. Case presentation We report a case of anti-epileptic-induced drug reaction with eosinophilia and systemic symptoms syndrome in an 18-year-old African-American man who presented with a five-day history of rash, periorbital and upper extremity edema, hepatitis and fever. Laboratory findings revealed an atypical lymphocytosis, eosinophilia, and elevated serum transaminases. No drug allergies were reported at the time of presentation, but phenytoin and levetiracetam therapy had been initiated five weeks prior to hospital admission for new-onset seizures. Both medications were discontinued on hospital admission, and after three days of high-dose corticosteroid therapy the patient experienced resolution of both his symptoms and laboratory markers of inflammation. Conclusion Given the significant mortality attributed to drug reaction with eosinophilia and systemic symptoms syndrome, medical personnel should be aware of the potential for this severe hypersensitivity reaction and should ensure close follow-up and offer anticipatory guidance when beginning any new medication, particularly anti-epileptic therapy. Early recognition of drug reaction with eosinophilia and systemic symptoms syndrome and initiation of appropriate therapy are imperative in limiting morbidity.

Therapy against organophosphate poisoning: The importance of anticholinergic drugs with antiglutamatergic properties

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Weissman, Ben Avi; Raveh, Lily

2008-01-01

Potent cholinesterase inhibitors (e.g., soman, sarin), induce a wide range of deleterious effects including convulsions, behavioral impairments and ultimately, death. Due to the likelihood of various scenarios of military or terrorist attacks by these and other chemical weapons, research has to be aimed at finding optimal therapies. Early accumulation of acetylcholine in synaptic clefts was suggested to trigger an array of toxic events including an excessive release of glutamate, culminating in the activation of its receptors. Stimulation of the N-Methyl-D-Aspartate (NMDA) subtype of these receptors was associated with the neuronal injury that initiates organophosphate-induced brain damage. The notion of a stepwise mechanism yielded treatments based on a combination of an immediate administration of enzyme reactivators and anticholinergic drugs. This strategy dramatically increased survival rates but did not abolish convulsions and failed to prevent the ensuing cognitive dysfunction. Efforts to improve this paradigm by adding anticonvulsants or antiglutamatergic drugs with anti-epileptic characteristics produced dubious results. Under these conditions, benactyzine and caramiphen, agents with anticholinergic and antiglutamatergic properties, provided improved protection when introduced as adjunct agents to oximes, reversible cholinesterase inhibitors and/or specific antimuscarinic drugs such as atropine. In contrast, the specific antimuscarinic drug scopolamine failed to block soman-induced changes in glutamatergic and behavioral parameters even when given prophylactically. These findings along with a large number of additional reports led towards the conclusion that the therapeutic advantage of drugs such as benactyzine and caramiphen could derive from their ability to modulate central cholinergic and glutamate neurotransmission

Health-related quality of life in epilepsy patients receiving anti-epileptic drugs at National Referral Hospitals in Uganda: a cross-sectional study.

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Nabukenya, Anne M; Matovu, Joseph K B; Wabwire-Mangen, Fred; Wanyenze, Rhoda K; Makumbi, Fredrick

2014-04-12

Epilepsy is a devastating disorder that impacts on patients' quality of life, irrespective of use of anti epileptic drugs (AEDs). This study estimates the health-related quality of life (HRQOL) and its associated predictors among epilepsy patients receiving AEDs. A total of 175 epilepsy patients already receiving AED for at least 3 months were randomly selected and interviewed from mental clinics at Mulago and Butabika national referral hospitals in Uganda between May - July 2011. A HRQOL index, the primary outcome, was constructed using items from Quality Of Life in Epilepsy Inventory (QOLIE-31) and the Hospital Anxiety and Depression Scale (HADS) questionnaires. The internal consistency and adequacy of these items was also computed using Cronbach's alpha and Kaiser-Meyer-Olkin tests. Partial correlations were used to evaluate the contribution of the health dimensions (mental, psychological, social, physical functioning and emotional well being) and, multiple linear regressions to determine factors independently associated with HRQOL. Just about half of the respondents (54%) were males, and nearly two thirds (62%) had received AEDs for at least 12 months. The average age was 26.6 years (SD = 11.1). The overall HRQOL mean score was 58 (SD = 13) on a scale of 0-100. The average scores of different dimensions or subscales ranged from 41 (physical) to 65 (psychological). At least three quarters (75%) of all subscales had good internal consistency and adequacy. The largest variations in the overall HRQOL were explained by social and mental functioning; each accounting for about 30% of the difference in the HRQOL but seizure control features explained a little (6%) variation. Factors negatively associated with HRQOL were poly-therapy (-1.16, p = 0.01) and frequency of seizures (-2.29, p = 0.00). Other factors associated with overall HRQOL included drug side effects, sex, marital status and education. Duration on AEDs was not a significant predictor of HRQOL. The HRQOL

Seizure characteristics and the use of anti-epileptic drugs in children and young people with brain tumours and epileptic seizures: Analysis of regional paediatric cancer service population.

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Pilotto, Chiara; Liu, Jo-Fen; Walker, David A; Whitehouse, William P

2018-03-21

Epileptic seizures complicate the management of childhood brain tumours. There are no published standards for clinical practice concerning risk factors, treatment selection or strategies to withdraw treatment with antiepileptic drugs (AED). we undertook a case note review of 120 patients with newly diagnosed brain tumours, referred to a regional paediatric cancer service. data was available on 117/120 (98%) children seizures. A cortical tumour location was associated with the highest risk of seizures (OR: 7.1; CI 95% 2.9-17.3). At a median follow up of 24 months (IQR 25°-75° : 15-48), 22/35 (63%) with seizures, had a single seizure episode, 15/35 (43%) were seizure free (SF) on AEDs, 13/35 (37%) were SF off AEDs, and 7/35 (20%) experienced continuing epileptic seizures. Overall 34/35 (97%) were treated with AEDs after a seizure, of whom 12/35 (35%) withdrew from AED medication, and although 4/35 (12%) had seizure relapse, all were after further acute events. The median duration of AED before withdrawal was 11 months (IQR 25°-75° 5-14 months), and the median follow up after withdrawal was 15 months (IQR 25°-75° 5-34 months). Seizures affect about 1/3rd of children and young people presenting with and being treated for brain tumours particularly when the tumour is in the cerebral cortex. The low risk of recurrent seizures after AED treatment justifies consideration of early withdrawal of AED after seizure control. Copyright © 2018. Published by Elsevier Ltd.

A double-blind, placebo-controlled interaction study between oxcarbazepine and carbamazepine, sodium valproate and phenytoin in epileptic patients.

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McKee, P J; Blacklaw, J; Forrest, G; Gillham, R A; Walker, S M; Connelly, D; Brodie, M J

1994-01-01

1. The effect of carbamazepine (CBZ), sodium valproate (VPA) and phenytoin (PHT) on the pharmacokinetics of oxcarbazepine (OXC) was explored in three groups of 12 epileptic patients taking one of these drug as monotherapy. 2. Each patient took a single 600 mg dose of OXC followed 7 days later by 3 weeks' treatment with OXC 300 mg thrice daily and matched placebo in random order. 3. Seven untreated patients, acting as controls, were prescribed the single OXC dose and 3 weeks' active treatment only. 4. In those patients completing the study, the area under the concentration-time curve (AUC) at steady-state for hydroxycarbazepine (OHCZ), the active metabolite of OXC, was significantly lower in the CBZ-treated group than in controls (P effects during treatment with OXC compared with one taking placebo (P < 0.01). 8. There were no important changes in cognitive function testing during administration of OXC compared with placebo. 9. Standard doses of OXC can be given as add-on therapy in epileptic patients receiving CBZ, VPA or PHT without producing a clinically relevant pharmacokinetic interaction. PMID:8148215

Dilemmas in diagnostics and therapy of rolandic epilepsy

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Škrijelj Fadil

2011-01-01

Full Text Available Introduction. It is considered that around 20%-30% of patients of all ages and in all continents have wrong epilepsy diagnoses. Diagnostic and consequential therapeutic errors appear, most often, when an adequate diagnostics is not applied. Benign focal epilepsy of childhoods with centrotemporal spikes-rolandic epilepsy, brings very often to diagnostic and therapeutic problems because of persistence of epilepticforms changes in an electroencephalography (EEG recording, several years after establishment of good control over seizures. Case report. We presented 8.5 years-old girl, with the first and the only epileptic seizure at the age of 5, during her sleep. With a clear correlation of EEG record, benign rolandic epilepsy was diagnosed, so the therapy with valproate was introduced. There were no seizures after three years of its implementation. Because of epileptic-forms changes that still persisted in EEG record during her sleep, it was suggested to further use valproate. However, after reconsidering all circumstances it was concluded that the AED should bee slowly reduced up to its exclusion. After a complete stoppage of the therapy, the patient did not have any epileptic seizure for nine months, although EEG still remained pathologically changed during her sleep. Conclusion. A changed EEG record in a patient with rolandic epilepsy must not be a predictor of continuation of antiepileptic drugs therapy, after 2-3 years of successful seizures remission.

Knowledge and attitude of epilepsy among secondary schools students (epileptic and non-epileptic) in Assiut city Egypt.

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Shehata, Ghaydaa A; Mahran, Dalia G

2011-06-01

This study was designed to assess knowledge and attitude with respect to epilepsy among secondary school students (epileptic and none) in Assiut city, Egypt. A cross sectional study was applied among secondary school students in Assiut city, Egypt. A 13-item questionnaire was self administered by 2226 students who selected randomly. All students either epileptic or non-epileptic had been heard about epilepsy. Only 7.1% of epileptic students and 8.5% of non-epileptic students thought that the epilepsy is a brain disease. Out of 2198 non-epileptic students, 28.4% thought that person with epilepsy (PWE) should not marry and 92% of them refused to marry from PWE. The correct knowledge of epilepsy was significantly positive correlated with positive attitude towards PWE. However, students still feel persons with epilepsy are stigmatized and are different from others. Secondary school students in Egypt have a vague knowledge about the etiology of epilepsy. Misconceptions about and negative attitudes towards epilepsy are unexpectedly high among those students. Copyright © 2011 Elsevier B.V. All rights reserved.

Algorithms for optimizing drug therapy

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Martin Lene

2004-07-01

Full Text Available Abstract Background Drug therapy has become increasingly efficient, with more drugs available for treatment of an ever-growing number of conditions. Yet, drug use is reported to be sub optimal in several aspects, such as dosage, patient's adherence and outcome of therapy. The aim of the current study was to investigate the possibility to optimize drug therapy using computer programs, available on the Internet. Methods One hundred and ten officially endorsed text documents, published between 1996 and 2004, containing guidelines for drug therapy in 246 disorders, were analyzed with regard to information about patient-, disease- and drug-related factors and relationships between these factors. This information was used to construct algorithms for identifying optimum treatment in each of the studied disorders. These algorithms were categorized in order to define as few models as possible that still could accommodate the identified factors and the relationships between them. The resulting program prototypes were implemented in HTML (user interface and JavaScript (program logic. Results Three types of algorithms were sufficient for the intended purpose. The simplest type is a list of factors, each of which implies that the particular patient should or should not receive treatment. This is adequate in situations where only one treatment exists. The second type, a more elaborate model, is required when treatment can by provided using drugs from different pharmacological classes and the selection of drug class is dependent on patient characteristics. An easily implemented set of if-then statements was able to manage the identified information in such instances. The third type was needed in the few situations where the selection and dosage of drugs were depending on the degree to which one or more patient-specific factors were present. In these cases the implementation of an established decision model based on fuzzy sets was required. Computer programs

Determination of a selection of anti-epileptic drugs and two active metabolites in whole blood by reversed phase UPLC-MS/MS and some examples of application of the method in forensic toxicology cases.

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Karinen, Ritva; Vindenes, Vigdis; Hasvold, Inger; Olsen, Kirsten Midtbøen; Christophersen, Asbjørg S; Øiestad, Elisabeth

2015-07-01

Quantitative determination of anti-epileptic drug concentrations is of great importance in forensic toxicology cases. Although the drugs are not usually abused, they are important post-mortem cases where the question of both lack of compliance and accidental or deliberate poisoning might be raised. In addition these drugs can be relevant for driving under the influence cases. A reversed phase ultra-performance liquid chromatography-tandem mass spectrometry method has been developed for the quantitative analysis of the anti-epileptic compounds carbamazepine, carbamazepine-10,11-epoxide, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, 10-OH-carbazepine, phenobarbital, phenytoin, pregabalin, and topiramate in whole blood, using 0.1 mL sample volume with methaqualone as internal standard. Sample preparation was a simple protein precipitation with acetonitrile and methanol. The diluted supernatant was directly injected into the chromatographic system. Separation was performed on an Acquity UPLC® BEH Phenyl column with gradient elution and a mildly alkaline mobile phase. The mass spectrometric detection was performed in positive ion mode, except for phenobarbital, and multiple reaction monitoring was used for drug quantification. The limits of quantification for the different anti-epileptic drugs varied from 0.064 to 1.26 mg/L in blood, within-day and day-to-day relative standard deviations from 2.2 to 14.7% except for phenobarbital. Between-day variation for phenobarbital was 20.4% at the concentration level of 3.5 mg/L. The biases for all compounds were within ±17.5%. The recoveries ranged between 85 and 120%. The corrected matrix effects were 88-106% and 84-110% in ante-mortem and post-mortem whole blood samples, respectively. Copyright © 2014 John Wiley & Sons, Ltd.

Limited efficacy of the ketogenic diet in the treatment of highly refractory epileptic spasms.

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Hussain, Shaun A; Shin, Ji Hyun; Shih, Evan J; Murata, Kristina K; Sewak, Sarika; Kezele, Michele E; Sankar, Raman; Matsumoto, Joyce H

2016-02-01

Numerous studies have suggested that the ketogenic diet is effective in the treatment of epileptic spasms, even in refractory cases. However, there has been very limited demonstration of prompt and complete (video-EEG confirmed) response. We set out to describe our center's experience with the ketogenic diet in the treatment of children with highly refractory epileptic spasms, with rigorous seizure outcome assessment. Children treated with the ketogenic diet for epileptic spasms between April, 2010 and June, 2014 were retrospectively identified. Seizure burden was tabulated at baseline and after 1, 3, 6, and 12-months of ketogenic diet exposure. Adverse events were similarly ascertained. We identified a cohort of 22 consecutive patients who received ketogenic diet therapy, with median age of onset of epileptic spasms of 5.2 (IQR 2.0-9.0) months, with diet initiation beginning a median of 26.4 (12.5-38.7) months after onset, and following a median of 7 (IQR 5-7) treatment failures. Only 2 patients exhibited a complete response during ketogenic diet exposure, and response was more reasonably attributed to alternative therapies in both cases. A modest early reduction in seizure frequency was not sustained beyond 1 month of diet exposure. The diet was well tolerated, and continued in 6 patients with subjective and/or partial response. In contrast to prior studies reporting substantial efficacy of the ketogenic diet, our findings suggest limited efficacy, albeit in a highly refractory cohort. Prospective studies in both refractory and new-onset populations, with both video-EEG confirmation of response and rigorous cognitive outcome assessment, would be of great value to more clearly define the utility of the ketogenic diet in the treatment of epileptic spasms. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Syndrome of Electrical Status Epilepticus During Sleep: Epileptic Encephalopathy Related to Brain Development.

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Chen, Xiao-Qiao; Zhang, Wei-Na; Hu, Lin-Yan; Liu, Meng-Jia; Zou, Li-Ping

2016-03-01

Epileptic encephalopathy with electrical status epilepticus during sleep is an age-related and self-limited disorder. The present study analyzed the etiology, demographics, and pathogenesis of patients with electrical status epilepticus during sleep to provide information on the diagnosis and therapy of this syndrome. The etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in patients admitted in Chinese People's Liberation Army General Hospital from 2009 to 2014 were retrospectively analyzed. Patients were classified into the genetic, structural-metabolic, and unknown groups according to the etiology. Demographics and clinical characteristics of all the patients were then analyzed and compared among groups. The etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in 75 patients mainly included benign childhood epilepsy with centrotemporal spikes, Landau-Kleffner syndrome, polymicrogyria, and migration disorders. Age at onset of epilepsy did not show a specific pattern, but age at onset of epileptic encephalopathy with electrical status epilepticus during sleep was concentrated at age 6-9 years. The mean age at onset of epilepsy in the genetic group was significantly older than that in the structural-metabolic group (P status epilepticus during sleep did not significantly differ between the two groups. Electrical status epilepticus during sleep is an epileptic encephalopathy related to brain development and presents an age-dependent occurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

Aspirin attenuates spontaneous recurrent seizures in the chronically epileptic mice.

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Zhu, Kun; Hu, Ming; Yuan, Bo; Liu, Jian-Xin; Liu, Yong

2017-08-01

Neuroinflammatory processes are pathologic hallmarks of both experimental and human epilepsy, and could be implicated in the neuronal hyperexcitability. Aspirin represents one of the non-selective nonsteroidal anti-inflammatory drugs with fewer side effects in long-term application. This study was carried out to assess the anti-epileptic effects of aspirin when administered during the chronic stage of temporal lobe epilepsy [TLE] in mice. The alteration of hippocampal neurogenesis was also examined for raising a possible mechanism underlying the protective effect of anti-inflammatory treatment in the TLE. Two months after pilocarpine-induced status epilepticus, the chronically epileptic mice were treated with aspirin (20 mg, 60 mg or 80 mg/kg) once a day for 10 weeks. Spontaneous recurrent seizures were monitored by video camera for 2 weeks. To evaluate the profile of hippocampal neurogenesis, the newly generated cells in the dentate gyrus were labeled by the proliferation marker BrdU. The newborn neurons that extended axons to CA3 area were visualized by cholera toxin B subunit retrograde tracing. Administration of aspirin with a dosage of 60 mg or 80 mg/kg initiated at 2 months after pilocarpine-induced status epilepticus significantly reduced the frequency and duration of spontaneous recurrent seizures. Aspirin treatment also increased the number of newborn neurons with anatomic integration through improving the survival of the newly generated cells. Aspirin treatment during the chronic stage of TLE could attenuate the spontaneous recurrent seizures in mice. Promotion of hippocampal neurogenesis and inhibition of COX-PGE2 pathway might partly contribute to this anti-epileptic effect. Highlights • Aspirin attenuates spontaneous recurrent seizures of chronically epileptic mice • Aspirin increases neurogenesis of chronically epileptic hippocampus by improving the survival of newly generated cells • Promotion of hippocampal neurogenesis and inhibition

Mutations of PTPN23 in developmental and epileptic encephalopathy

KAUST Repository

Sowada, Nadine

2017-10-31

Developmental and epileptic encephalopathies (DEE) are a heterogeneous group of neurodevelopmental disorders with poor prognosis. Recent discoveries have greatly expanded the repertoire of genes that are mutated in epileptic encephalopathies and DEE, often in a de novo fashion, but in many patients, the disease remains molecularly uncharacterized. Here, we describe a new form of DEE in patients with likely deleterious biallelic variants in PTPN23. The phenotype is characterized by early onset drug-resistant epilepsy, severe and global developmental delay, microcephaly, and sometimes premature death. PTPN23 encodes a tyrosine phosphatase with strong brain expression, and its knockout in mouse is embryonically lethal. Structural modeling supports a deleterious effect of the identified alleles. Our data suggest that PTPN23 mutations cause a rare severe form of autosomal-recessive DEE in humans, a finding that requires confirmation.

Clarithromycine-Induced Ventricular Tachycardia in a Geriatric Patient Using Multiple Drugs

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Gulsah Karaoren

2016-07-01

Full Text Available Long QT syndrome is a cardiac repolarization disorder, which can be either idiopathic or congenital, and cause sudden cardiac death. The iatrogenic form is generally associated with drugs or electrolyte imbalance. Although prolonged QT interval is frequently seen due to antiarrhythmic agents, it can also be seen with antibiotics or anti-epileptics. Adverse drug interaction can manifest in several clinicopathological forms in elder individuals. In such cases, potential adverse effects of drugs used should be taken into consideration before prescribing additional drugs. Here, we present a case of clarithromycine-induced ventricular arrhythmia accompanied by QT prolongation on the third day of therapy, and the subsequent therapeutic approach, in a 91-year-old man. The patient was taking multiple drugs due to comorbid conditions and was prescribed clarithromycine therapy in the intensive care unit.

Sirenomelia after phenobarbital and carbamazepine therapy in pregnancy.

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Tica, Oana Sorina; Tica, Andrei Adrian; Brailoiu, Cristina Gabriela; Cernea, Nicolae; Tica, Vlad Iustin

2013-06-01

Epilepsy still remains a serious challenge for any obstetrician due to the potential teratogenicity of all antiepileptics. However, without appropriate maternal therapy the seizures can reappear, with direct negative impact on fetus. Currently, sirenomelia is the most severe caudal pole dysgenesis, consequent to an abnormal vascular supply development in the fetal lower body. We report a stillborn, GA/LMP = 37 weeks, delivered by an epileptic woman, who received in the first four months of pregnancy phenobarbital (PH) 0.1 g/day and carbamazepine (CMZ) 0.4 g/day, followed only by PH 0.1 g/day, until delivery. The stillborn, weighing 2200 g, presented sirenomelia type II, with some of its "classic" features: oligohydramnios, absence of kidneys, bladder, rectum, uterus, and a single umbilical artery. Some other "particularities" included: no Potter's facies and no significant cardio-pulmonary abnormalities. Since PH and CMZ alone are responsible, commonly, for mild abnormalities, we hypothesized that combined therapy with PH and CMZ (both strong enzyme-inductors, especially PH) potentiated their teratogenicity, by producing supplementary quantities of epoxides and/or other oxides, which accumulated in the fetal tissues. Except for sirenomelia, all other mild abnormalities, theoretically associated with "fetal CMZ and/or PH syndrome," are rarely observed, fact which demonstrates the drug-drug interactions between the two antiepileptics. This report highlights the possibility that PH/CBZ therapy during fetal organogenesis can induce sirenomelia, by a synergistic teratogenic effect and support the recommendation to use only one drug in pregnant epileptic women. A careful ultrasound monitoring of these patients is mandatory due to the teratogenic risk of both seizures and therapy. Copyright © 2013 Wiley Periodicals, Inc.

[Nootropics and antioxidants in the complex therapy of symptomatic posttraumatic epilepsy].

Science.gov (United States)

Savenkov, A A; Badalian, O L; Avakian, G N

2013-01-01

To study the possibility of application of nootropics and antioxidants in the complex antiepileptic therapy, we examined 75 patients with symptomatic focal posttraumatic epilepsy. A statistically significant reduction in the number of epileptic seizures, improvement of cognitive function and quality of life of the patients as well as a decrease in the severity of depression and epileptic changes in the EEG were identified. The potentiation of antiepileptic activity of basic drugs, normalization of brain's electrical activity and reduction in EEG epileptiform activity, in particular coherent indicators of slow-wave activity, were noted after treatment with the antioxidant mexidol. A trend towards the improvement of neuropsychological performance and quality of life was observed. There was a lack of seizure aggravation typical of many nootropic drugs. Thus, phenotropil and mexidol can be recommended for complex treatment of symptomatic posttraumatic epilepsy.

[Combination drug therapy in leprosy].

Science.gov (United States)

Terencio de las Aguas, J

1983-01-01

The importance of polichemotherapy in multibacilar leprosy (LL and LD) in patients without any previous therapy as in those diagnosticated and under monotherapy most of all in the resistance patients is presented. Sulphones, clofazimine and rifampicine are selected as first rate drugs and protionamide-etionamide as second rate drugs. The therapy plans with the association of two and three drugs and the convenience of continuing indefinitely with at least one of the drugs are presented insisting on the advantages of the clofazimine-sulphones and rifampicine-sulphones associations. The necessity of immunotherapy for recover of celular immunity against the bacilus, is the only form of preventing relapses and drug resistance.

Drug interactions between common illicit drugs and prescription therapies.

Science.gov (United States)

Lindsey, Wesley T; Stewart, David; Childress, Darrell

2012-07-01

The aim was to summarize the clinical literature on interactions between common illicit drugs and prescription therapies. Medline, Iowa Drug Information Service, International Pharmaceutical Abstracts, EBSCO Academic Search Premier, and Google Scholar were searched from date of origin of database to March 2011. Search terms were cocaine, marijuana, cannabis, methamphetamine, amphetamine, ecstasy, N-methyl-3,4-methylenedioxymethamphetamine, methylenedioxymethamphetamine, heroin, gamma-hydroxybutyrate, sodium oxybate, and combined with interactions, drug interactions, and drug-drug interactions. This review focuses on established clinical evidence. All applicable full-text English language articles and abstracts found were evaluated and included in the review as appropriate. The interactions of illicit drugs with prescription therapies have the ability to potentiate or attenuate the effects of both the illicit agent and/or the prescription therapeutic agent, which can lead to toxic effects or a reduction in the prescription agent's therapeutic activity. Most texts and databases focus on theoretical or probable interactions due to the kinetic properties of the drugs and do not fully explore the pharmacodynamic and clinical implications of these interactions. Clinical trials with coadministration of illicit drugs and prescription drugs are discussed along with case reports that demonstrate a potential interaction between agents. The illicit drugs discussed are cocaine, marijuana, amphetamines, methylenedioxymethamphetamine, heroin, and sodium oxybate. Although the use of illicit drugs is widespread, there are little experimental or clinical data regarding the effects of these agents on common prescription therapies. Potential drug interactions between illicit drugs and prescription drugs are described and evaluated on the Drug Interaction Probability Scale by Horn and Hansten.

[Analysis of gene mutation of early onset epileptic spasm with unknown reason].

Science.gov (United States)

Yang, X; Pan, G; Li, W H; Zhang, L M; Wu, B B; Wang, H J; Zhang, P; Zhou, S Z

2017-11-02

Objective: To summarize the gene mutation of early onset epileptic spasm with unknown reason. Method: In this prospective study, data of patients with early onset epileptic spasm with unknown reason were collected from neurological department of Children's Hospital of Fudan University between March 2016 and December 2016. Patients with known disorders such as infection, metabolic, structural, immunological problems and known genetic mutations were excluded. Patients with genetic disease that can be diagnosed by clinical manifestations and phenotypic characteristics were also excluded. Genetic research methods included nervous system panel containing 1 427 epilepsy genes, whole exome sequencing (WES), analysis of copy number variation (CNV) and karyotype analysis of chromosome. The basic information, phenotypes, genetic results and the antiepileptic treatment of patients were analyzed. Result: Nine of the 17 cases with early onset epileptic spasm were boys and eight were girls. Patients' age at first seizure onset ranged from 1 day after birth to 8 months (median age of 3 months). The first hospital visit age ranged from 1 month to 2 years (median age of 4.5 months). The time of following-up ranged from 8 months to 3 years and 10 months. All the 17 patients had early onset epileptic spasm. Video electroencephalogram was used to monitor the spasm seizure. Five patients had Ohtahara syndrome, 10 had West syndrome, two had unclear classification. In 17 cases, 10 of them had detected pathogenic genes. Nine cases had point mutations, involving SCN2A, ARX, UNC80, KCNQ2, and GABRB3. Except one case of mutations in GABRB3 gene have been reported, all the other cases had new mutations. One patient had deletion mutation in CDKL5 gene. One CNV case had 6q 22.31 5.5MB repeats. Ten cases out of 17 were using 2-3 antiepileptic drugs (AEDs) and the drugs had no effect. Seven cases used adrenocorticotropic hormone (ACTH) and prednisone besides AEDs (a total course for 8 weeks

Homocysteine, folic acid and vitamin B12 levels in serum of epileptic ...

African Journals Online (AJOL)

The mechanism of this association with epileptogenesis has not been clearly understood, although there is emerging evidence to support the unfavorable effects of some anti-epileptic drugs (AEDs) on the plasma homocysteine (Hcy) concentrations. The aim of this study was to uncover the relationship between the levels of ...

Drug therapy of leprosy

Directory of Open Access Journals (Sweden)

A. A. Kubanov

2016-01-01

Full Text Available Leprosy (Hansen’s disease is a chronic granulomatous bacterial infection mainly affecting the skin and peripheral nervous system yet also involving other organs and systems as a result of a pathological process. The causative agent of leprosy - Mycobacterium leprae - is an obligate intracellular microorganism. Despite the removal of a threat of a leprosy epidemic, European countries still record outbreaks of the disease mainly among migrants coming from endemic areas. A golden standard of the treatment of leprosy is a WHO-recommended combined drug therapy comprising drugs such as dapsone, clofazimine and rifampicin. The article provides current data on the mechanisms of action, efficacy and safety of these drugs and their combined scheme of treatment obtained as a result of clinical trials. Moreover, it also reviews new regimens of the drug therapy of leprosy including those with the use of drugs from the group of fluoroquinols as well as immunotherapy of the disease.

Recurrent epileptic Wernicke aphasia.

Science.gov (United States)

Sahaya, Kinshuk; Dhand, Upinder K; Goyal, Munish K; Soni, Chetan R; Sahota, Pradeep K

2010-04-15

We report a patient with recurrent epileptic Wernicke aphasia who prior to this presentation, had been misdiagnosed as transient ischemic attacks for several years. This case report emphasizes the consideration of epileptic nature of aphasia when a clear alternate etiology is unavailable, even when EEG fails to show a clear ictal pattern. We also present a brief discussion of previously reported ictal aphasias. Copyright 2010 Elsevier B.V. All rights reserved.

Epileptic Negative Myoclonus as the First and Only Symptom in a Challenging Diagnosis of Benign Epilepsy With Centrotemporal Spikes

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Jing Chen MD

2017-07-01

Full Text Available Objective: To investigate the clinical and neurophysiological characteristics of epileptic negative myoclonus as the first and only ictal symptom of benign epilepsy with centrotemporal spikes. Methods: Electrophysiological evaluations included polygraphic recordings with simultaneous video electroencephalogram monitoring and tests performed with patient’s upper limb outstretched in standing posture. Epileptic negative myoclonus manifestations, electrophysiological features, and responses to antiepileptic drugs were analyzed. Results: The authors report 2 patients with benign epilepsy with centrotemporal spikes, who had epileptic negative myoclonus as the first and only seizure type. Video electroencephalogram monitoring results showed that their negative myoclonus seizures were emanating from the contralateral central and the parietal regions. Epileptic negative myoclonus was controlled by administration of valproate and levetiracetam. Conclusion: Epileptic negative myoclonus can be the first and only seizure type of benign epilepsy with centrotemporal spikes, and long-term follow-up monitoring should be the care for the recurrence and/or presence of other types of seizures.

A study on epileptic negative myoclonus in atypical benign partial epilepsy of childhood.

Science.gov (United States)

Yang, Zhixian; Liu, Xiaoyan; Qin, Jiong; Zhang, Yuehua; Bao, Xinhua; Chang, Xingzhi; Wang, Shuang; Wu, Ye; Xiong, Hui

2009-04-01

To investigate the clinical and neurophysiological characteristics, particularly therapeutic considerations, of epileptic negative myoclonus (ENM) in atypical benign partial epilepsy (ABPE) of childhood. From 1998 to 2006, 14/242 patients with benign children epilepsy with centrotemporal spikes (BECTS) were diagnosed as having ABPE with ENM. In all 14 patients, we performed video-EEG monitoring along with tests with the patient's arms outstretched; 6/14 patients were also simultaneously underwent surface electromyogram (EMG). ENM manifestations, electrophysiological features, and responses to antiepileptic drugs were analyzed. In all cases, ENM developed after the onset of epilepsy and during antiepileptic drug therapy, and the appearance of ENM were corresponding to EEG findings of high-amplitude spikes followed by a slow wave in the contralateral motor areas with secondary generalization. This was further confirmed by time-locked silent EMG. During ENM occurrence or recurrence, habitual seizures and interictal discharges were exaggerated. In some patients, the changes in antiepileptic drug regimens in relation to ENM appearance included add-on therapy with carbamazepine, oxcarbazepine, and phenobarbital or withdrawal of valproate. ENM was controlled in most cases by administration of various combinations of valproate, clonazepam, and corticosteroids. The incidence of ENM or ABPE in our center was approximately 5.79%. A combination of video-EEG monitoring with the patient's arms outstretched and EMG is essential to identify ENM. The aggravation of habitual seizures and interictal discharges indicate ENM. Some antiepileptic drugs, such as carbamazepine, oxcarbazepine, and phenobarbital, may be related to ENM occurrence during spontaneous aggravation of ABPE. Various combinations of valproate, benzodiazepines, and corticosteroids are relatively effective for treating ENM that occurs in ABPE.

Cognitive Dysfunctions in Epileptic Syndromes

Directory of Open Access Journals (Sweden)

Semih Ayta

2014-05-01

Full Text Available Some children with epilepsy display a low level of intelligence, learning disabilities, attention deficit hyperactivity disorder, mood disorders and anxiety. Besides specific learning disabilities like reading, writing, arithmetics, learning problems may involve other major areas of intellectual functions such as speech and language, attention, memory, fine motor coordination. Even in the presence of common pathology that leads to epilepsy and mental dysfunctions, seizures cause additional cognitive problems. Age at seizure onset, type of seizures and epileptic syndromes are some variables that determine the effect of epilepsy on cognition. As recurrent seizures may have some negative impact on the developing brain, the use of antiepileptic drugs should be considered not only to aim reducing seizures but also to prevent possible seizure-induced cortical dysfunctions. Epilepsy is a disorder requiring a complicated psychological adjustment for the patients and indeed is a disease that affects the whole family. Thus, the management of epilepsy must include educational, psychotherapeutic and behavioral interventions as well as drug treatment.

Cerebellar atrophy in epileptic patients

International Nuclear Information System (INIS)

Taneva, N.

1991-01-01

52 patients with epileptic seizures of different form, frequency and duration who had received long term treatment with anticonvulsive drugs were examined on Siretom 2000, a brain scanner of II generation. 6 standard incisions were made in all patients in the area of cerebellum, side ventricules and high convexity. Additional scanning with an incision width of 5 mm was made when pathological changes were detected. There were found 3 cases of cerebellar atrophy, 3 - cerebral atrophy, 1 - combined atrophy and 4 - with other changes. It was difficult to establish any relation between the rerebellar atrophy and the type of anticonvulsant used because treatment had usually been complex. 1 fig., 1 tab., 4 refs

Antiretroviral therapy: current drugs.

Science.gov (United States)

Pau, Alice K; George, Jomy M

2014-09-01

The rapid advances in drug discovery and the development of antiretroviral therapy is unprecedented in the history of modern medicine. The administration of chronic combination antiretroviral therapy targeting different stages of the human immunodeficiency virus' replicative life cycle allows for durable and maximal suppression of plasma viremia. This suppression has resulted in dramatic improvement of patient survival. This article reviews the history of antiretroviral drug development and discusses the clinical pharmacology, efficacy, and toxicities of the antiretroviral agents most commonly used in clinical practice to date. Published by Elsevier Inc.

Multidisciplinary approach to hospitalized epileptic children and their families

Directory of Open Access Journals (Sweden)

Angela Cristina Pontes

2006-06-01

Full Text Available Objective: Epilepsy is the most frequent diagnosis in the ward;due to the high degree of complexity of its investigation andtreatment, the objective of this work was to proceed to an analysisof the interventions of the team with hospitalized epileptic childrenand their families. Methods: The data were obtained from theclinical handbooks and individual registers of the specialties.Results: There were 235 elective admissions, 88 regarding theEpilepsy. The services for specialties were distributed among those88 epileptic children: physiotherapy (34%, psychology (41% andoccupational therapy (88.6%. Conclusion: Given the severity ofthe social and biological sequelae associated with the diagnosisof epilepsy and the need for a family intervention, themultidisciplinary work focused on the child, in stimulationinterventions and promotion of his/her development, with a viewto minimize the sequelae; and providing the family with orientationand support, in order to give them more elaborate strategies forcoping with the disease and improve conditions for supplying postdischargeinfant treatment.

Drug therapy in headache.

Science.gov (United States)

Weatherall, Mark W

2015-06-01

All physicians will encounter patients with headaches. Primary headache disorders are common, and often disabling. This paper reviews the principles of drug therapy in headache in adults, focusing on the three commonest disorders presenting in both primary and secondary care: tension-type headache, migraine and cluster headache. The clinical evidence on the basis of which choices can be made between the currently available drug therapies for acute and preventive treatment of these disorders is presented, and information given on the options available for the emergency parenteral treatment of refractory migraine attacks and cluster headache. © Royal College of Physicians 2015. All rights reserved.

Drug delivery system and radiation therapy

International Nuclear Information System (INIS)

Shibata, Tokushi

2005-01-01

This paper describes the review of radiation therapy, neutron capture therapy (NCT) and drug delivery system for the latter. In cancer radiation therapy, there are problems of body movement like breathing, needless irradiation of normal tissues, difficulty to decide the correct irradiation position and tumor morphology. NCT has advantages to overcome these, and since boron has a big cross section for thermal neutron, NPT uses the reaction 10 B(n, α) 7 Li in the target cancer which previously incorporated the boron-containing drug. During the period 1966-1996, 246 patients were treated with this in Japan and the treatment has been continued thereafter. The tasks for NCT are developments of drug delivery system efficient to deliver the drug into the tumor and of convenient neutron source like the accelerator. (S.I.)

Behaviour therapy for obesity treatment considering approved drug therapy

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Wasem, Jürgen

2008-05-01

Full Text Available Introduction: Obesity is a worldwide health problem whose prevalence is on the increase. Many obesity-associated diseases require intensive medical treatment and are the cause of a large proportion of health-related expenditures in Germany. Treatment of obesity includes nutritional, exercise and behaviour therapy, usually in combination. The goal of behaviour therapy for obesity is to bring about a long-term alteration in the eating and exercise habits of overweight and obese individuals. Under certain circumstances, drug treatment may be indicated. Objectives: What is the effectiveness of behaviour therapy for obesity considering approved drugs reduce weight under medical, economic, ethical-social and legal aspects? Methods: A systematic review was conducted using relevant electronic literature databases. Publications chosen according to predefined criteria are evaluated by approved methodical standards of the evidence-based medicine systematically and qualitatively. Results: In total 18 studies, included one HTA and one meta-analysis could be identified according to the predefined inclusion criteria. Three studies compare behaviour therapy to other therapy forms (advice or instruction on nutritional changes, physical activity or a combination of the two, six studies evaluate different forms of behaviour therapy, four studies and four studies compare behaviour therapies mediated by Internet or telephone. Three studies could be identified examining the effect of the combination of behaviour and drug therapy. Furthermore one HTA and one meta-analysis could be included in the evaluation. The behaviour therapy in comparison with other therapy forms reveals a higher effectiveness. In comparison of the different therapeutic approaches of the behaviour therapy intensive behaviour therapy forms and group therapy show a higher effectiveness. Studies related to behaviour therapy based on media support demonstrate a weight reduction both through the

Differential Effect of Neuropeptides on Excitatory Synaptic Transmission in Human Epileptic Hippocampus

DEFF Research Database (Denmark)

Ledri, Marco; Sorensen, Andreas T.; Madsen, Marita G.

2015-01-01

therapy is an evolving innovative approach that may prove useful for clinical applications. In animal models of temporal lobe epilepsy (TLE), gene therapy treatments based on viral vectors encoding NPY or galanin have been shown to effectively suppress seizures. However, how this translates to human TLE...... remains unknown. A unique possibility to validate these animal studies is provided by a surgical therapeutic approach, whereby resected epileptic tissue from temporal lobes of pharmacoresistant patients are available for neurophysiological studies in vitro. To test whether NPY and galanin have...

Autism spectrum disorder and epileptic encephalopathy: common causes, many questions.

Science.gov (United States)

Srivastava, Siddharth; Sahin, Mustafa

2017-01-01

Epileptic encephalopathies represent a particularly severe form of epilepsy, associated with cognitive and behavioral deficits, including impaired social-communication and restricted, repetitive behaviors that are the hallmarks of autism spectrum disorder (ASD). With the advent of next-generation sequencing, the genetic landscape of epileptic encephalopathies is growing and demonstrates overlap with genes separately implicated in ASD. However, many questions remain about this connection, including whether epileptiform activity itself contributes to the development of ASD symptomatology. In this review, we compiled a database of genes associated with both epileptic encephalopathy and ASD, limiting our purview to Mendelian disorders not including inborn errors of metabolism, and we focused on the connection between ASD and epileptic encephalopathy rather than epilepsy broadly. Our review has four goals: to (1) discuss the overlapping presentations of ASD and monogenic epileptic encephalopathies; (2) examine the impact of the epilepsy itself on neurocognitive features, including ASD, in monogenic epileptic encephalopathies; (3) outline many of the genetic causes responsible for both ASD and epileptic encephalopathy; (4) provide an illustrative example of a final common pathway that may be implicated in both ASD and epileptic encephalopathy. We demonstrate that autistic features are a common association with monogenic epileptic encephalopathies. Certain epileptic encephalopathy syndromes, like infantile spasms, are especially linked to the development of ASD. The connection between seizures themselves and neurobehavioral deficits in these monogenic encephalopathies remains open to debate. Finally, advances in genetics have revealed many genes that overlap in ties to both ASD and epileptic encephalopathy and that play a role in diverse central nervous system processes. Increased attention to the autistic features of monogenic epileptic encephalopathies is warranted for

[Unusual dreams in epileptics].

Science.gov (United States)

Boldyrev, A I

1984-01-01

The author discusses bizarre dreams characteristic of epileptics and never occurring in normal subjects which have an important practical implication especially for early detection of epilepsy and the prevention of severe forms of the disease. This group of dreams includes vivid nightmares with vital fear, dreams not infrequently transforming into pro-dream states; persistently repeated stereotyped dreams and dreams with invariably the same unpleasant sensations representing an isolated aura of subsequent epileptic attacks. Diagnostically important may also be dreams with the symptoms of derealization and depersonalization, vague dream images and the deja vu phenomenon.

Efficacy of fish liver oil and propolis as neuroprotective agents in pilocarpine epileptic rats treated with valproate.

Science.gov (United States)

Mannaa, Fathia; El-Shamy, Karima A; El-Shaikh, Kamal A; El-Kassaby, Mahitab

2011-09-01

To evaluate the action of fish liver oil and propolis in pilocarpine epileptic rats treated with the anticonvulsant drug valproate. Seven groups of rats were treated daily for six months: control; fish liver oil (0.4ml/kg b.w); propolis (50mg/kg b.w); pilocarpine-treated rats (epileptic control); epileptic rats treated with valproate (400mg/kg b.w); groups 6 and 7, epileptic rats treated with valproate plus fish liver oil or propolis. Pilocarpine administration caused a significant increase in hippocampal dopamine and serotonin levels accompanied with a significant decrease in their levels in serum. Lipid peroxidation level and LDH activity in hippocampus were significantly increased after pilocarpine treatment whereas Na(+)/K(+)-ATPase activity and total antioxidant capacity were significantly decreased compared to the controls. Animals treated with the combined treatments showed a significant improvement in tested parameters towards the normal values of the control. Fish liver oil and propolis when given in combination with valproate, neuroprotected against the neurophysiological disorders induced by pilocarpine epilepsy in rats. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Artificial intelligence in drug combination therapy.

Science.gov (United States)

Tsigelny, Igor F

2018-02-09

Currently, the development of medicines for complex diseases requires the development of combination drug therapies. It is necessary because in many cases, one drug cannot target all necessary points of intervention. For example, in cancer therapy, a physician often meets a patient having a genomic profile including more than five molecular aberrations. Drug combination therapy has been an area of interest for a while, for example the classical work of Loewe devoted to the synergism of drugs was published in 1928-and it is still used in calculations for optimal drug combinations. More recently, over the past several years, there has been an explosion in the available information related to the properties of drugs and the biomedical parameters of patients. For the drugs, hundreds of 2D and 3D molecular descriptors for medicines are now available, while for patients, large data sets related to genetic/proteomic and metabolomics profiles of the patients are now available, as well as the more traditional data relating to the histology, history of treatments, pretreatment state of the organism, etc. Moreover, during disease progression, the genetic profile can change. Thus, the ability to optimize drug combinations for each patient is rapidly moving beyond the comprehension and capabilities of an individual physician. This is the reason, that biomedical informatics methods have been developed and one of the more promising directions in this field is the application of artificial intelligence (AI). In this review, we discuss several AI methods that have been successfully implemented in several instances of combination drug therapy from HIV, hypertension, infectious diseases to cancer. The data clearly show that the combination of rule-based expert systems with machine learning algorithms may be promising direction in this field. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

FOCAL EPILEPTIC MYOCLONUS IN KOZHEVNIKOV–RASMUSSEN SYNDROME

Directory of Open Access Journals (Sweden)

N. E. Kvaskova

2016-01-01

Full Text Available The article presents the clinical, electroencephalographic (EEG and neuroimaging features, as well as the results of treatment of patients with focal epileptic myoclonus (FEM with the Kozhevnikov–Rasmussen syndrome (KRS. FEM in KRS-patients was identified in 11 cases, accounting for 0.9 % of all the cases of epilepsy with the onset of seizures up to 18 years (n = 1261. The age at onset of KRS ranged from 3 to 21 years (average – 9.2 ± 5.7 years. In the active period of the disease of all patients in the clinical picture the active FEM appeared and increasing frequency of the secondary generalized seizures (SGS. In addition SGS and FEM, the clinical picture of the disease in most patients (91 % the focal motor (clonic and the somatosensory focal seizures were observed. As the disease progressed, the FEM became more pronounced in frequency and intensity, seized more muscle groups, localizing mainly in the muscles of the trunk and limbs. The typical EEG pattern of FEM patients with KRS was regional epileptiform activity that occurs in the structure of the continued regional slowing localizing maximum of the fronto-central-temporal region. During the magnetic resonance tomography of the brain in dynamics all the patients observed the increase in total cortical hemiatrophy. In all the cases, the appointment of antiepileptic therapy resulted in a slowing of the FEM, however, a complete remission was reached at none of the patients. Two patients were made surgical treatment of epilepsy. In one case remission of epileptic seizures was observed after right-side hemispherotomy. Our study showed that FEM is very resistant type of epileptic seizures. This fact calls for the identification of the FEM at the early stages of the disease with the purpose to improve the prognosis, as well as for an earlier surgical treatment.

Multimodality localization of epileptic foci

Science.gov (United States)

Desco, Manuel; Pascau, Javier; Pozo, M. A.; Santos, Andres; Reig, Santiago; Gispert, Juan D.; Garcia-Barreno, Pedro

2001-05-01

This paper presents a multimodality approach for the localization of epileptic foci using PET, MRI and EEG combined without the need of external markers. Mutual Information algorithm is used for MRI-PET registration. Dipole coordinates (provided by BESA software) are projected onto the MRI using a specifically developed algorithm. The four anatomical references used for electrode positioning (nasion, inion and two preauricular points) are located on the MRI using a triplanar viewer combined with a surface-rendering tool. Geometric transformation using deformation of the ideal sphere used for dipole calculations is then applied to match the patient's brain size and shape. Eight treatment-refractory epileptic patients have been studied. The combination of the anatomical information from the MRI, hipoperfusion areas in PET and dipole position and orientation helped the physician in the diagnosis of epileptic focus location. Neurosurgery was not indicated for patients where PET and dipole results were inconsistent; in two cases it was clinically indicated despite the mismatch, showing a negative follow up. The multimodality approach presented does not require external markers for dipole projection onto the MRI, this being the main difference with previous methods. The proposed method may play an important role in the indication of surgery for treatment- refractory epileptic patients.

Potential drug therapies for the treatment of fibromyalgia.

Science.gov (United States)

Lawson, Kim

2016-09-01

Fibromyalgia (FM) is a common, complex chronic widespread pain condition is characterized by fatigue, sleep disturbance and cognitive dysfunction. Treatment of FM is difficult, requiring both pharmacological and non-pharmacological approaches, with an empiric approach to drug therapy focused toward individual symptoms, particularly pain. The effectiveness of current medications is limited with many patients discontinuing use. A systemic database search has identified 26 molecular entities as potential emerging drug therapies. Advances in the understanding of the pathophysiology of FM provides clues to targets for new medications. Investigation of bioamine modulation and α2δ ligands and novel targets such as dopamine receptors, NMDA receptors, cannabinoid receptors, melatonin receptors and potassium channels has identified potential drug therapies. Modest improvement of health status in patients with FM has been observed with drugs targeting a diverse range of molecular mechanisms. No single drug, however, offered substantial efficacy against all the symptoms characteristic of FM. Identification of new and improved therapies for FM needs to address the heterogeneity of the condition, which suggests existence of patient subgroups, the relationship of central and peripheral aspects of the pathophysiology and a requirement of combination therapy with drugs targeting multiple molecular mechanisms.

The offspring of epileptic mother.

Science.gov (United States)

Tamer, S K; Misra, S; Jaiswal, S

1996-01-01

The offspring of an epileptic mother is an issue-currently getting attention because of its several implications. A complex interaction between epilepsy during pregnancy and its adverse impact on foetus, labor, neonate, congenital malformation, psychosocial and medico-social concern and treatment challenges of such cases is increasingly being realised. Some of the significant observations has been reviewed extensively in this article. Maternal epilepsy is likely to adversely affect the off-spring at its various stages of development amounting to increased morbidity and mortality. Increased seizure frequency during pregnancy with resultant increased risk is well documented but its mechanism is poorly understood. Low apgar score, increased still birth rates (1.3 to 14%) in offspring of epileptic mother (OEM) is reported. So also, the neonatal and perinatal deaths are twice more common in OEMS than normal control. Small for dates, and prematurity in OEM is reported to be 7 to 10% and 4-11% respectively. Adverse impact on labor and delivery like preclampsia, abruptio placentae, polyhydramnios, assisted delivery, cesarean section and IUGR poses particular challenges to the obstetrician. Pediatrician's alertness is needed to anticipate and deal with the bleeding manifestation due to deficiency of Vit-K dependent clotting factors and various anticonvulsant drug (AED) withdrawal symptoms. Significant risk of developing congenital malformation is the result of epilepsy perse and the AED used during pregnancy. AED exposure leads to other distinct clinical syndromes, the orofacial clefts and cardiac anomalies being the commonest manifestation. Epilepsy in mother but not in father has significant adverse impact. Management strategies in the context of available observation has been discussed.

Drug therapy smartens up

Science.gov (United States)

Martin, Christian

2015-11-01

The submission of the first 'smart pill' for market approval, combined with progress in the European nanomedicine landscape, illustrates the positive outlook for drug therapy and health monitoring, explains Christian Martin.

Electrical stimulation of the epileptic focus in absence epileptic WAG/RIJ rats: assessment of local and network excitability

NARCIS (Netherlands)

Luttjohann, A.K.; Zhang, S.W.; Peijper, R.A.G. de; Luijtelaar, E.L.J.M. van

2011-01-01

[Objective] The study aims to investigate whether there is a higher excitability in the deep cortical layers of the pen-oral region of the somatosensory cortex as compared to other cortical regions in absence epileptic WAG/Rij rats and whether this is unique for this type of epileptic rats, as would

Metabolomics has the potential to improve drug therapy

DEFF Research Database (Denmark)

Stage, Claus; Jürgens, Gesche; Dalhoff, Kim Peder

2014-01-01

Until now drug therapy has primarily been controlled by dose titration on the basis of effects and side effects. However, a lot of people being treated with a drug experience too little effect or too many side effects. Therefore it will be advantageous to improve drug therapy and make it even more...

Compare Of the West Syndrome with Other Syndromes in the Epileptic Encephalopathy - Kosovo Experience

Science.gov (United States)

Zeka, Naim; Gërguri, Abdurrahim; Bejiqi, Ramush; Retkoceri, Ragip; Vuciterna, Armend

2017-01-01

BACKGROUND: West Syndrome (WS) represents as a specific epileptic encephalopathy characterised with a unique type of attacks, called infantile spasms, severe forms of abnormalities in electroencephalographic (EEG) records as a hypsarythmias and delays in the psychomotoric development. The characteristics of the disease, mostly affecting male gender, are infantile spasms and typical findings in EEG as a hypsarythmia. Infantile spasms are a consequence of many factors in the undeveloped brain. AIM: We aimed: (1) to see the incidence of the illness and the spreading out because of gender in rapport with other syndromes in the epileptic encephalopathies group; (2) to show principles of the treatment for the illness; and (3) to present the effects of the disease in the psycho-motoric development of affected children. METHODS: The study was designed as a cross-sectional study of the patients with epileptic encephalopathies, treated in Paediatric Clinic in Prishtina, from 1st of January 2013 until the 31st of December 2015. RESULTS: From the cohort group of 97 children diagnosed with epileptic encephalopathies, in 14 of them clinical and EEG signs of WS were noted. The earliest age of disease manifestation was 74 days (± 63.8 days). On the group of children with WS, 13 of them with Natrium Valpropat were treated, with the doses of 301.9 mg (± 64.1). From the cohort group, in 89 children (91.8%) psychomotoric retardation was documented, within the higher reoccurrence in the undifferentiated epileptic encephalopathies (96%) and the WS (78.6%). CONCLUSION: WS is a frequent disease of the encephalopathies with the epileptogenic framework. The resistance in anticonvulsive therapy is huge, and psychomotoric retardation follows a big percentage of children with this syndrome. PMID:29362620

Treating Lennox–Gastaut syndrome in epileptic pediatric patients with third-generation rufinamide

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Jessica Gresham

2010-09-01

Full Text Available Jessica Gresham1, Lea S Eiland2,3, Allison M Chung2,41Auburn University, Harrison School of Pharmacy (AUHSOP, 2Department of Pharmacy Practice, AUHSOP, 3University of Alabama, School of Medicine, Huntsville Regional Medical Campus, 4University of South Alabama School of Medicine, Department of Pediatrics, Mobile, Alabama, USAAbstract: Lennox–Gastaut syndrome (LGS is a rare but debilitating pediatric epileptic encephalopathy characterized by multiple intractable seizure types. Treatment of LGS is challenging because of the small number of antiepileptic drugs (AEDs which are effective for this syndrome, as well as the need for polytherapy in the majority of patients. This review focuses on the treatment of LGS with rufinamide, a recently approved third-generation AED with reported efficacy as adjunctive therapy for LGS. All relevant papers identified through a PubMed search on the treatment of LGS with rufinamide were reviewed. To date, the literature suggests improvements in seizure frequency for pediatric patients with LGS on rufinamide. Rufinamide appears to be especially effective for atonic or drop attack seizures. Rufinamide also displays a favorable adverse event profile compared with the older anticonvulsants, as well as a minimal number of drug interactions, making it a promising option for the adjunctive treatment of seizures associated with LGS.Keywords: epilepsy, Lennox-Gastaut syndrome, pediatrics, seizure, rufinamide

Potential effects of valproate and oxcarbazepine on growth velocity and bone metabolism in epileptic children- a medical center experience.

Science.gov (United States)

Lin, Chien-Ming; Fan, Hueng-Chuen; Chao, Tsu-Yi; Chu, Der-Ming; Lai, Chi-Chieh; Wang, Chih-Chien; Chen, Shyi-Jou

2016-05-03

Children with longstanding use of antiepileptic drugs (AEDs) are susceptible to developing low bone mineral density and an increased fracture risk. However, the literature regarding the effects of AEDs on growth in epileptic children is limited. The aim of this study was to investigate the potential effects of valproate (VPA) and/or oxcarbazepine (OXC) therapy on growth velocity and bone metabolism. Seventy-three ambulatory children (40 boys and 33 girls) with epilepsy, aged between 1 and 18 years (mean age 9.8 ± 4.1 years), were evaluated for growth velocity before and for 1 year after VPA and/or OXC treatment. The bone resorption marker serum tartrate-resistant acid phosphatase 5b (TRAcP5b) and the bone formation marker serum bone-specific alkaline phosphatase (BAP) were measured post-AEDs therapy for 1 year. The difference in growth velocity (ΔHt) and body weight change (ΔWt) between pre- and post-AEDs treatment were -1.0 ± 2.8 cm/year (P effect of VPA and/or OXC therapy on dysregulation of bone metabolism might play a crucial role in physical growth.

International veterinary epilepsy task force recommendations for systematic sampling and processing of brains from epileptic dogs and cats

DEFF Research Database (Denmark)

Matiasek, Kaspar; Pumarola I Batlle, Martí; Rosati, Marco

2015-01-01

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fai...

Daytime encopresis associated with gland mal epileptic seizures: case report.

Science.gov (United States)

Oyatsi, D P

2005-08-01

Sphincteric incontinence of stool and urine are not unusual features of generalised epileptic seizures. Isolated secondary encopresis as a manifestation of an epileptic seizure is unusual. This report is of, a four year old boy, with daytime secondary non-retentive encopresis. The onset of encopresis was preceded by several episodes of nocturnal generalised tonic clonic epileptic seizures. An electroencephalogram showed features consistent with complex partial seizures. He was commenced on anti-epileptic treatment with phenytoin sodium, and by the third day of treatment, the patient had achieved stool control.

The Short-Term Effects of Ketogenic Diet on Cardiac Ventricular Functions in Epileptic Children.

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Doksöz, Önder; Çeleğen, Kübra; Güzel, Orkide; Yılmaz, Ünsal; Uysal, Utku; İşgüder, Rana; Çeleğen, Mehmet; Meşe, Timur

2015-09-01

Our primary aim was to determine the short-term effects of a ketogenic diet on cardiac ventricular function in patients with refractory epilepsy. Thirty-eight drug-resistant epileptic patients who were treated with a ketogenic diet were enrolled in this prospective study. Echocardiography was performed on all patients before beginning the ketogenic diet and after the sixth month of therapy. Two-dimensional, M-mode, color flow, spectral Doppler, and pulsed-wave tissue Doppler imaging measurements were performed on all patients. The median age of the 32 patients was 45.5 months, and 22 (57.8%) of them were male. Body weight, height, and body mass index increased significantly at the sixth month of therapy when compared with baseline values (P 0.05). Doppler flow indices of mitral annulus and tricuspid annulus velocity of patients at baseline and month 6 showed no significant differences (P > 0.05). Tricuspid annular E/A ratio was lower at month 6 (P 0.05), there was a decrease in Ea velocity and Ea/Aa ratio gathered from tricuspid annulus at month 6 compared with baseline (P ketogenic diet does not impair left ventricular functions in children with refractory epilepsy; however, it may be associated with a right ventricular diastolic dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

Definition and classification of epilepsy. Classification of epileptic seizures 2016

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K. Yu. Mukhin

2017-01-01

Full Text Available Epilepsy is one of the most common neurological diseases, especially in childhood and adolescence. The incidence varies from 15 to 113 cases per 100 000 population with the maximum among children under 1 year old. The prevalence of epilepsy is high, ranging from 5 to 8 cases (in some regions – 10 cases per 1000 children under 15 years old. Classification of the disease has great importance for diagnosis, treatment and prognosis. The article presents a novel strategy for classification of epileptic seizures, developed in 2016. It contains a number of brand new concepts, including a very important one, saying that some seizures, previously considered as generalized or focal only, can be, in fact, both focal and generalized. They include tonic, atonic, myoclonic seizures and epileptic spasms. The term “secondarily generalized seizure” is replace by the term “bilateral tonic-clonic seizure” (as soon as it is not a separate type of epileptic seizures, and the term reflects the spread of discharge from any area of cerebral cortex and evolution of any types of focal seizures. International League Against Epilepsy recommends to abandon the term “pseudo-epileptic seizures” and replace it by the term “psychogenic non-epileptic seizures”. If a doctor is not sure that seizures have epileptic nature, the term “paroxysmal event” should be used without specifying the disease. The conception of childhood epileptic encephalopathies, developed within this novel classification project, is one of the most significant achievements, since in this case not only the seizures, but even epileptiform activity can induce severe disorders of higher mental functions. In addition to detailed description of the new strategy for classification of epileptic seizures, the article contains a comprehensive review of the existing principles of epilepsy and epileptic seizures classification.

Knowledge about epilepsy among teachers and epileptic patients

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Maria F. Valls Tosetti

1991-09-01

Full Text Available 223 epileptics patients and their families and 136 teachers from public and private schools were submitted to similar questionnaires related to inheritance, transmission, cure, complilcation rates, care during seizures, need for information on the disease, habits, comparison with other diseases and to the educational and social performances of epileptics. Cure and complication nates accounted for the main differences between those populations. Epileptics could recognize a bigger number of complications but still expected to be cured from the disease. The majority of teachers and patients have never been informed about epilepsy and this finding was related to the big number of equivocal answers obtained from them. Put together, the data showed that social and educational performance of epileptic patients could be disturbed by medical and social parameters. Some, of them could be improved by an educational program towards these aspects of epilepsy.

Consciousness in Non-Epileptic Attack Disorder

OpenAIRE

Reuber, M.; Kurthen, M.

2011-01-01

Non-epileptic attack disorder (NEAD) is one of the most important differential diagnoses of epilepsy. Impairment of\\ud consciousness is the key feature of non-epileptic attacks (NEAs). The first half of this review summarises the clinical research\\ud literature featuring observations relating to consciousness in NEAD. The second half places this evidence in the wider context\\ud of the recent discourse on consciousness in neuroscience and the philosophy of mind. We argue that studies of consci...

Clinical Presentation of Epilepsy among Adult Sudanese Epileptic ...

African Journals Online (AJOL)

Objective: To study the pattern of clinical presentation of epilepsy among adult Sudanese epileptic patients. Methods: 120 patients with epilepsy were included in a prospective cross-sectional study. Setting: The study was conducted at Sheik Mohamed Kheir Friday Epileptic Clinic .Duration: May 2003 Oct 2006. Results: ...

Dramatic effect of levetiracetam in early-onset epileptic encephalopathy due to STXBP1 mutation.

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Dilena, Robertino; Striano, Pasquale; Traverso, Monica; Viri, Maurizio; Cristofori, Gloria; Tadini, Laura; Barbieri, Sergio; Romeo, Antonino; Zara, Federico

2016-01-01

Syntaxin Binding Protein 1 (STXBP1) mutations determine a central neurotransmission dysfunction through impairment of the synaptic vesicle release, thus causing a spectrum of phenotypes varying from syndromic and non-syndromic epilepsy to intellectual disability of variable degree. Among the antiepileptic drugs, levetiracetam has a unique mechanism of action binding SV2A, a glycoprotein of the synaptic vesicle release machinery. We report a 1-month-old boy manifesting an epileptic encephalopathy with clonic seizures refractory to phenobarbital, pyridoxine and phenytoin that presented a dramatic response to levetiracetam with full epilepsy control and EEG normalization. Genetic analysis identified a novel de novo heterozygous mutation (c.[922A>T]p.[Lys308(∗)]) in the STXBP1 gene that severely affects the protein. The observation of a dramatic efficacy of levetiracetam in a case of STXBP1 epileptic encephalopathy refractory to other antiepileptic drugs and considerations regarding the specific mechanism of action of levetiracetam modulating the same system affected by STXBP1 mutations support the hypothesis that this drug may be able to reverse specifically the disease epileptogenic abnormalities. Further clinical observations and laboratory studies are needed to confirm this hypothesis and eventually lead to consider levetiracetam as the first choice treatment of patients with suspected or confirmed STXBP1-related epilepsies. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Prevalence of Autism among Epileptic Children Referring to Imam Reza Clinic and Comparing to Control Group (non Epileptic Children During2013-2014

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LS mohammadijahromi

2017-06-01

Discussion: According to this study, the prevalence of autism among epileptic children is higher than non epileptic ones. As the age of the onset of seizure is lower the prevalence of autism will be higher. Also, the prevalence of autism among epileptic children will be higher as abnormal findings of imaging and known etiologies of seizureincrease. Loss of significant correlations among prevalence of autism and some variables of seizure can be due to few numbers of autistic cases, which were diagnosed in this study comparing with previous studies.

Temporal epileptic seizures and occupational exposure to solvents

DEFF Research Database (Denmark)

Jacobsen, M; Bælum, Jesper; Bonde, J P

1994-01-01

Long term exposure to organic solvents is usually not considered as a possible cause of chronic epileptic seizures. A case that shows a remarkable coincidence between exposure to organic solvents and occurrence of epileptic seizures is reported. The man was a 58 year old sign writer with lifelong...

Is there anything distinctive about epileptic deja vu?

Science.gov (United States)

Warren-Gash, Charlotte; Zeman, Adam

2014-02-01

Déjà vu can occur as an aura of temporal lobe epilepsy and in some psychiatric conditions but is also common in the general population. It is unclear whether any clinical features distinguish pathological and physiological forms of déjà vu. 50 epileptic patients with ictal déjà vu, 50 non-epileptic patients attending general neurology clinics and 50 medical students at Edinburgh University were recruited. Data were collected on demographic factors, the experience of déjà vu using a questionnaire based on Sno's Inventory for Déjà Vu Experiences Assessment, symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale as well as seizure characteristics, anti-epileptic medications, handedness, EEG and neuroimaging findings for epileptic patients. 73.5% of neurology patients, 88% of students and (by definition) all epilepsy patients had experienced déjà vu. The experience of déjà vu itself was similar in the three groups. Epileptic déjà vu occurred more frequently and lasted somewhat longer than physiological déjà vu. Epilepsy patients were more likely to report prior fatigue and concentrated activity, associated derealisation, olfactory and gustatory hallucinations, physical symptoms such as headaches, abdominal sensations and fear. After controlling for study group, anxiety and depression scores were not associated with déjà vu frequency. Déjà vu is common and qualitatively similar whether it occurs as an epileptic aura or normal phenomenon. However ictal déjà vu occurs more frequently and is accompanied by several distinctive features. It is distinguished primarily by 'the company it keeps'.

Long-Term Intake of Uncaria rhynchophylla Reduces S100B and RAGE Protein Levels in Kainic Acid-Induced Epileptic Seizures Rats.

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Tang, Nou-Ying; Lin, Yi-Wen; Ho, Tin-Yun; Cheng, Chin-Yi; Chen, Chao-Hsiang; Hsieh, Ching-Liang

2017-01-01

Epileptic seizures are crucial clinical manifestations of recurrent neuronal discharges in the brain. An imbalance between the excitatory and inhibitory neuronal discharges causes brain damage and cell loss. Herbal medicines offer alternative treatment options for epilepsy because of their low cost and few side effects. We established a rat epilepsy model by injecting kainic acid (KA, 12 mg/kg, i.p.) and subsequently investigated the effect of Uncaria rhynchophylla (UR) and its underlying mechanisms. Electroencephalogram and epileptic behaviors revealed that the KA injection induced epileptic seizures. Following KA injection, S100B levels increased in the hippocampus. This phenomenon was attenuated by the oral administration of UR and valproic acid (VA, 250 mg/kg). Both drugs significantly reversed receptor potentiation for advanced glycation end product proteins. Rats with KA-induced epilepsy exhibited no increase in the expression of metabotropic glutamate receptor 3, monocyte chemoattractant protein 1, and chemokine receptor type 2, which play a role in inflammation. Our results provide novel and detailed mechanisms, explaining the role of UR in KA-induced epileptic seizures in hippocampal CA1 neurons.

Mental Development of Children with Non-epileptic Paroxysmal States in Medical History

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Turovskaya N.G.,

2015-10-01

Full Text Available The author studied mental functions disorders in children with a history of paroxysmal states of various etiologies and compared mental development disorder patterns in patients with epileptic and non-epileptic paroxysms. Study sample were 107 children, aged 6 to 10 years. The study used experimental psychological and neuropsychological techniques. According to the empirical study results, non-epileptic paroxysms unlike epileptic much less combined with a number of mental functions disorders and intelligence in general. However, non-epileptic paroxysmal states as well as epileptic seizure associated with increasing activity exhaustion and abnormal function of the motor analyzer (dynamic and kinesthetic dyspraxia. Visual memory disorders and modal-nonspecific memory disorders have more pronounced importance in the mental ontogenesis structure in children with convulsive paroxysms compared to children with cerebral pathology without paroxysms history

Laboratory markers in personalized drug therapy

NARCIS (Netherlands)

Geerts, A.F.J.

2012-01-01

During the last decade two major trends have influenced the thinking about the benefit-risk balance in drug therapy.The first trend showed that this balance is not only determined by the interaction of the pharmacological properties of the drug with the patient’s (patho)physiological profile, but is

COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES): statistical and economic analysis plan for a randomised controlled trial.

Science.gov (United States)

Robinson, Emily J; Goldstein, Laura H; McCrone, Paul; Perdue, Iain; Chalder, Trudie; Mellers, John D C; Richardson, Mark P; Murray, Joanna; Reuber, Markus; Medford, Nick; Stone, Jon; Carson, Alan; Landau, Sabine

2017-06-06

Dissociative seizures (DSs), also called psychogenic non-epileptic seizures, are a distressing and disabling problem for many patients in neurological settings with high and often unnecessary economic costs. The COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES) trial is an evaluation of a specifically tailored psychological intervention with the aims of reducing seizure frequency and severity and improving psychological well-being in adults with DS. The aim of this paper is to report in detail the quantitative and economic analysis plan for the CODES trial, as agreed by the trial steering committee. The CODES trial is a multicentre, pragmatic, parallel group, randomised controlled trial performed to evaluate the clinical effectiveness and cost-effectiveness of 13 sessions of cognitive behavioural therapy (CBT) plus standardised medical care (SMC) compared with SMC alone for adult outpatients with DS. The objectives and design of the trial are summarised, and the aims and procedures of the planned analyses are illustrated. The proposed analysis plan addresses statistical considerations such as maintaining blinding, monitoring adherence with the protocol, describing aspects of treatment and dealing with missing data. The formal analysis approach for the primary and secondary outcomes is described, as are the descriptive statistics that will be reported. This paper provides transparency to the planned inferential analyses for the CODES trial prior to the extraction of outcome data. It also provides an update to the previously published trial protocol and guidance to those conducting similar trials. ISRCTN registry ISRCTN05681227 (registered on 5 March 2014); ClinicalTrials.gov NCT02325544 (registered on 15 December 2014).

FT-Raman, FT-IR and UV-visible spectral investigations and ab initio computations of anti-epileptic drug: Vigabatrin

Science.gov (United States)

Edwin, Bismi; Joe, I. Hubert

2013-10-01

Vibrational analysis of anti-epileptic drug vigabatrin, a structural GABA analog was carried out using NIR FT-Raman and FTIR spectroscopic techniques. The equilibrium geometry, various bonding features and harmonic vibrational wavenumbers were studied using density functional theory method. The detailed interpretation of the vibrational spectra has been carried out with the aid of VEDA.4 program. Vibrational spectra, natural bond orbital analysis and optimized molecular structure show clear evidence for the effect of electron charge transfer on the activity of the molecule. Predicted electronic absorption spectrum from TD-DFT calculation has been compared with the UV-vis spectrum. The Mulliken population analysis on atomic charges and the HOMO-LUMO energy were also calculated. Good consistency is found between the calculated results and experimental data for the electronic absorption as well as IR and Raman spectra. The blue-shifting of the Csbnd C stretching wavenumber reveals that the vinyl group is actively involved in the conjugation path. The NBO analysis confirms the occurrence of intramolecular hyperconjugative interactions resulting in ICT causing stabilization of the system.

Pharmacogenetic evaluation of ABCB1, Cyp2C9, Cyp2C19 and methylene tetrahydrofolate reductase polymorphisms in teratogenicity of anti-epileptic drugs in women with epilepsy

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Manna Jose

2014-01-01

Full Text Available Aim: Pregnancy in women with epilepsy (WWE who are on anti-epileptic drugs (AEDs has two- to three-fold increased risk of fetal malformations. AEDs are mostly metabolized by Cyp2C9, Cyp2C19 and Cyp3A4 and transported by ABCB1. Patients on AED therapy can have folate deficiency. We hypothesize that the polymorphisms in ABCB1, Cyp2C9, Cyp2C19 and methylene tetrahydrofolate reductase (MTHFR might result in differential expression resulting in differential drug transport, drug metabolism and folate metabolism, which in turn may contribute to the teratogenic impact of AEDs. Materials and Methods: The ABCB1, Cyp2C9, Cyp2C19 and MTHFR polymorphisms were genotyped for their role in teratogenic potential and the nature of teratogenecity in response to AED treatment in WWE. The allelic, genotypic associations were tested in 266 WWE comprising of 143 WWE who had given birth to babies with WWE-malformation (WWE-M and 123 WWE who had normal offsprings (WWE-N. Results: In WWE-M, CC genotype of Ex07 + 139C/T was overrepresented (P = 0.0032 whereas the poor metabolizer allele FNx012 and FNx012 FNx012 genotype of CYP2C219 was significantly higher in comparison to WWE-N group (P = 0.007 and P = 0.005, respectively. All these observations were independent of the nature of malformation (cardiac vs. non cardiac malformations. Conclusion: Our study indicates the possibility that ABCB1 and Cyp2C19 may play a pivotal role in the AED induced teratogenesis, which is independent of nature of malformation. This is one of the first reports indicating the pharmacogenetic role of Cyp2C19 and ABCB1 in teratogenesis of AED in pregnant WWE.

Spiritual self-schema therapy, drug abuse, and HIV.

Science.gov (United States)

Marcotte, David; Avants, S Kelly; Margolin, Arthur

2003-01-01

This case report describes the use of Spiritual Self-Schema (3-S) therapy in the treatment of an HIV-positive inner-city drug user maintained on methadone and referred for additional treatment due to unremitting cocaine use. 3-S therapy is a manual-guided intervention based on cognitive self-schema theory. Its goal is to help the patient create, elaborate, and make accessible a cognitive schema--the "spiritual" self-schema-that is incompatible with drug use and other HIV risk behaviors. 3-S therapy facilitates a cognitive shift from the habitual activation of the "addict" self-schema, with its drug-related cognitions, scripts and action plans, to the "spiritual" self-schema, with its associated repertoire of harm reduction beliefs and behaviors.

Dose-Dependent Effect of Curcumin on Learning and Memory Deficit in Kainate-Epileptic Rats

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Zahra Kiasalari

2014-09-01

Full Text Available Background & objectives : Epileptic seizures accompany disturbances in learning, memory, and cognitive skills. With regard to antiepileptic potential of curcumin and its beneficial effect on memory, the effect of its administration on learning and memory in kainate-epileptic rats was investigated.   Methods: Forty male rats were divided into sham, positive control ( valproate-treated epileptic, epileptic, and two curcumin-treated epileptic groups. Rat model of epilepsy was induced by unilateral intrahippocampal administration of 4 μg of kainate per rat. Rats received intraperitoneal injection of curcumin (50 and 100 mg/kg daily for 1 week before surgery. For evaluation of learning and memory, initial (IL and step-through latencies (STL were determined using passive avoidance test and alternation behavior percentage was obtained according to Y maze test.   Results: Regarding IL, there was no significant difference between the groups. In contrast, STL significantly decreased in curcumin-50-treated epileptic group (p<0.05 (a change from 263.1 to 184.5 s. However, this parameter significantly increased in curcumin-100-treated epileptic group as compared to epileptic group (p<0.01 (a change from 263.1 to 220.3 s. In addition, STL was also significantly higher in valproic acid-treated epileptic group versus epileptic group (p<0.05 (a change from 145.7 to 210.3 s. Alternation percentage was also significantly higher in curcumin-50- and curcumin-100-treated epileptic groups relative to epileptic group (p<0.05 (a change from 60.5 to 77.6 and 80.3%.   Conclusion: Curcumin could dose-dependently enhance the consolidation and recall in epileptic animals and could improve spatial memory in such animals.

Nanomedicine of synergistic drug combinations for cancer therapy - Strategies and perspectives.

Science.gov (United States)

Zhang, Rui Xue; Wong, Ho Lun; Xue, Hui Yi; Eoh, June Young; Wu, Xiao Yu

2016-10-28

Nanomedicine of synergistic drug combinations has shown increasing significance in cancer therapy due to its promise in providing superior therapeutic benefits to the current drug combination therapy used in clinical practice. In this article, we will examine the rationale, principles, and advantages of applying nanocarriers to improve anticancer drug combination therapy, review the use of nanocarriers for delivery of a variety of combinations of different classes of anticancer agents including small molecule drugs and biologics, and discuss the challenges and future perspectives of the nanocarrier-based combination therapy. The goal of this review is to provide better understanding of this increasingly important new paradigm of cancer treatment and key considerations for rational design of nanomedicine of synergistic drug combinations for cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of music therapy on drug therapy of adult psychiatric outpatients: A pilot randomised controlled study

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Mario Degli Stefani

2016-10-01

Full Text Available Objective: Framed in the patients’ engagement perspective, the current study aims to determine the effects of group music therapy in addition to drug care in comparison with drug care in the treatment of psychiatric outpatients. Method: Participants (n = 27 with ICD-10 diagnoses of F20 (schizophrenia, F25 (schizoaffective disorders, F31 (bipolar affective disorder, F32 (depressive episode and F60 (specific personality disorders were randomised to receive group music therapy plus standard care (48 weekly sessions of two hours or standard care only. The clinical measures included dosages of neuroleptics, benzodiazepines, mood stabilisers and antidepressants. Results: The participants who received group music therapy demonstrated greater improvement in drug dosage relative to neuroleptics than those who did not receive group music therapy. Antidepressants had an increment for both groups that was significant only for the control group. Benzodiazepines and mood stabilisers did not show any significant change in either group. Conclusions: Group music therapy combined with standard drug care is effective for controlling neuroleptic drug dosages in adult psychiatric outpatients who received group music therapy. We discuss the likely applications of group music therapy in psychiatry and the possible contribution of music therapy in improving the psychopathological condition of adult outpatients. In addition, the implications for the patient-centred perspective were also discussed.

Effects of Music Therapy on Drug Therapy of Adult Psychiatric Outpatients: A Pilot Randomized Controlled Study

Science.gov (United States)

Degli Stefani, Mario; Biasutti, Michele

2016-01-01

Objective: Framed in the patients’ engagement perspective, the current study aims to determine the effects of group music therapy in addition to drug care in comparison with drug care in addition to other non-expressive group activities in the treatment of psychiatric outpatients. Method: Participants (n = 27) with ICD-10 diagnoses of F20 (schizophrenia), F25 (schizoaffective disorders), F31 (bipolar affective disorder), F32 (depressive episode), and F60 (specific personality disorders) were randomized to receive group music therapy plus standard care (48 weekly sessions of 2 h) or standard care only. The clinical measures included dosages of neuroleptics, benzodiazepines, mood stabilizers, and antidepressants. Results: The participants who received group music therapy demonstrated greater improvement in drug dosage with respect to neuroleptics than those who did not receive group music therapy. Antidepressants had an increment for both groups that was significant only for the control group. Benzodiazepines and mood stabilizers did not show any significant change in either group. Conclusion: Group music therapy combined with standard drug care was effective for controlling neuroleptic drug dosages in adult psychiatric outpatients who received group music therapy. We discussed the likely applications of group music therapy in psychiatry and the possible contribution of music therapy in improving the psychopathological condition of adult outpatients. In addition, the implications for the patient-centered perspective were also discussed. PMID:27774073

[Experience of rapid drug desensitization therapy in the treatment of mycobacterial disease].

Science.gov (United States)

Sasaki, Yuka; Kurashima, Atsuyuki; Morimoto, Kozo; Okumura, Masao; Watanabe, Masato; Yoshiyama, Takashi; Ogata, Hideo; Gotoh, Hajime; Kudoh, Shoji; Suzuki, Hiroaki

2014-11-01

Drugs for tuberculosis and non-tuberculosis mycobacterial diseases are limited. In particular, no new drugs for non-tuberculosis mycobacterial disease have been developed in recent years. Antimycobacterial drugs have many adverse reactions, for which drug desensitization therapy has been used. Rapid drug desensitization (RDD) therapy, including antituberculosis drugs and clarithromycin, has been implemented in many regions in Europe and the United States. We investigated the validity of RDD therapy in Japan. We report our experience with RDD therapy in 13 patients who developed severe drug allergy to antimycobacterial treatment. The desensitization protocol reported by Holland and Cernandas was adapted. The underlying diseases were 7 cases of pulmonary Mycobacterium avium complex disease and 6 cases of pulmonary tuberculosis. Isoniazid was readministered in 2 (100%) of 2 patients; rifampicin, in 8 (67.7%) of 12 patients; ethambutol, in 4 (67.7%) of 6 patients; and clarithromycin, in 2 (100%) of 2 patients. In Japan, the desensitization therapy recommended by the Treatment Committee of the Japanese Society for Tuberculosis have been implemented generally. We think RDD therapy is effective and safe as the other desensitization therapy. We will continue to investigate the efficiency of RDD therapy in patients who had discontinued antimycobacterial treatment because of the drug allergic reaction.

Genetic epileptic encephalopathies: is all written into the DNA?

Science.gov (United States)

Striano, Pasquale; de Jonghe, Peter; Zara, Federico

2013-11-01

Epileptic encephalopathy is a condition in which epileptic activity, clinical or subclinical, is thought to be responsible for any disturbance of cognition, behavior, or motor control. However, experimental evidence supporting this clinical observation are still poor and the causal relationship between pharmacoresistant seizures and cognitive outcome is controversial. In the past two decades, genetic studies shed new light onto complex mechanisms underlying different severe epileptic conditions associated with intellectual disability and behavioral abnormalities, thereby providing important clues on the relationship between seizures and cognitive outcome. Dravet syndrome is a childhood disorder associated with loss-of-function mutations in SCN1A and is characterized by frequent seizures and severe cognitive impairment, thus well illustrating the concept of epileptic encephalopathy. However, it is difficult to determine the causative role of the underlying sodium channel dysfunction and that of the consequent seizures in influencing cognitive outcome in these children. It is also difficult to demonstrate whether a recognizable profile of cognitive impairment or a definite behavioral phenotype exists. Data from the laboratory and the clinics may provide greater insight into the degree to which epileptic activity may contribute to cognitive impairment in individual syndromes. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Methadone maintenance therapy as evidence based drug abuse ...

African Journals Online (AJOL)

Methadone maintenance therapy as evidence based drug abuse planning in ... drugs are being used as artificial problem-solvers such as frustrations, stress or ... Drug use is a problem to users when it begins to cause some damage to their ...

[Subacute encephalopathy with epileptic seizures in an alcoholic patient].

Science.gov (United States)

Kozian, R; Otto, F G

2000-09-01

We introduce a case of a 66 year-old male with chronic alcoholism who suffered from confusion, Wernicke-aphasia and epileptic seizures. Several EEG revealed periodic lateralized epileptiform discharges. The patient's case resembles the symptoms of a subacute encephalopathy with epileptic seizures which can occur in alcoholics.

Antiepileptic drugs and bone metabolism

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Labban Barbara

2006-09-01

Full Text Available Abstract Anti-epileptic medications encompass a wide range of drugs including anticonvulsants, benzodiazepines, enzyme inducers or inhibitors, with a variety effects, including induction of cytochrome P450 and other enzyme, which may lead to catabolism of vitamin D and hypocalcemia and other effects that may significantly effect the risk for low bone mass and fractures. With the current estimates of 50 million people worldwide with epilepsy together with the rapid increase in utilization of these medications for other indications, bone disease associated with the use of anti-epileptic medications is emerging as a serious health threat for millions of people. Nevertheless, it usually goes unrecognized and untreated. In this review we discuss the pathophysiologic mechanisms of bone disease associated with anti-epileptic use, including effect of anti-epileptic agents on bone turnover and fracture risk, highlighting various strategies for prevention of bone loss and associated fractures a rapidly increasing vulnerable population.

A guided interview process to improve student pharmacists' identification of drug therapy problems.

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Rovers, John; Miller, Michael J; Koenigsfeld, Carrie; Haack, Sally; Hegge, Karly; McCleeary, Erin

2011-02-10

To measure agreement between advanced pharmacy practice experience students using a guided interview process and experienced clinical pharmacists using standard practices to identify drug therapy problems. Student pharmacists enrolled in an advanced pharmacy practice experience (APPE) and clinical pharmacists conducted medication therapy management interviews to identify drug therapy problems in elderly patients recruited from the community. Student pharmacists used a guided interview tool, while clinical pharmacists' interviews were conducted using their usual and customary practices. Student pharmacists also were surveyed to determine their perceptions of the interview tool. Fair to moderate agreement was observed on student and clinical pharmacists' identification of 4 of 7 drug therapy problems. Of those, agreement was significantly higher than chance for 3 drug therapy problems (adverse drug reaction, dosage too high, and needs additional drug therapy) and not significant for 1 (unnecessary drug therapy). Students strongly agreed that the interview tool was useful but agreed less strongly on recommending its use in practice. The guided interview process served as a useful teaching aid to assist student pharmacists to identify drug therapy problems.

Long-Term Intake of Uncaria rhynchophylla Reduces S100B and RAGE Protein Levels in Kainic Acid-Induced Epileptic Seizures Rats

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Nou-Ying Tang

2017-01-01

Full Text Available Epileptic seizures are crucial clinical manifestations of recurrent neuronal discharges in the brain. An imbalance between the excitatory and inhibitory neuronal discharges causes brain damage and cell loss. Herbal medicines offer alternative treatment options for epilepsy because of their low cost and few side effects. We established a rat epilepsy model by injecting kainic acid (KA, 12 mg/kg, i.p. and subsequently investigated the effect of Uncaria rhynchophylla (UR and its underlying mechanisms. Electroencephalogram and epileptic behaviors revealed that the KA injection induced epileptic seizures. Following KA injection, S100B levels increased in the hippocampus. This phenomenon was attenuated by the oral administration of UR and valproic acid (VA, 250 mg/kg. Both drugs significantly reversed receptor potentiation for advanced glycation end product proteins. Rats with KA-induced epilepsy exhibited no increase in the expression of metabotropic glutamate receptor 3, monocyte chemoattractant protein 1, and chemokine receptor type 2, which play a role in inflammation. Our results provide novel and detailed mechanisms, explaining the role of UR in KA-induced epileptic seizures in hippocampal CA1 neurons.

Personalized Drug Therapy in Cystic Fibrosis: From Fiction to Reality.

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de Lima Marson, Fernando Augusto; Bertuzzo, Carmen Silvia; Ribeiro, Jose Dirceu

2015-01-01

Personalized drug therapy for cystic fibrosis (CF) is a long-term dream for CF patients, caregivers, physicians and researchers. After years of study, the fiction of personalized treatment has turned to hope. Basic information about CFTR mutations classes and new treatments is needed if we are to deal properly with the new CF era. The problems involved in this issue, however, should be evaluated with greater care and attention. VX-770 is a new drug available to treat CF patients with some class III CFTR mutations and other drugs are being studied regarding other classes. The scientific literature has constantly given information about each therapy, both in vitro and in vivo. The hope is increasing. Nevertheless the "scientific world" still lacks information about patients' reality and daily health related practical needs. Clinical trials have showed good evaluation of some drugs so far, but clinical response is a wide spectrum yet to be analyzed: CFTR mutations spectrum, costs related to the treatment with new drugs (for VX-770 therapy), variability of CF clinical expression, limitations to test in vitro drugs, absence of good clinical markers to evaluate drug response, absence of long-term studies and with patients below six years old, multidrug treatment used to improve the expression response, and finally, the most important problem, who will benefit from the new drugs therapy, are issues that constitute a barrier that should be overcome. Personalized drug therapy may not be a fiction anymore, but it is not yet a reality for all CF patients.

[Epilepsy and epileptic syndromes during the first year of life].

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Durá-Travé, T; Yoldi-Petri, M E; Hualde-Olascoaga, J; Etayo-Etayo, V

To analyse the epidemiological characteristics and the relative distribution of the different types of epilepsy and epileptic syndromes during the first year of life. An analysis was performed of the patient records of all patients with epilepsy diagnosed during their first year of life who were submitted to a developmental check-up in the year 2007. The sample consisted of 60 patients (27 boys and 33 girls). Epidemiological and clinical data were collected, together with the findings from complementary examinations. The diagnostic criteria applied were those of the International League Against Epilepsy. The mean age at the time of diagnosis was 6.3 months. The mean follow-up time was 7.6 years. The aetiology was symptomatic in 40 cases (66.7%), cryptogenic in 16 (26.7%) and idiopathic in four cases (6.7%). Neuroimaging tests detected abnormalities in 34 patients (56.7%). West's syndrome (30%), symptomatic focal epilepsies (23.3%) and epilepsies linked to specific syndromes (16.7%) were the epileptic syndromes with the highest prevalence. Learning disabilities were observed in 82.5% of the children. Most epilepsies that present during the first year of life are symptomatic and/or cryptogenic, and are accompanied by psychoneurological impairment and/or resistance to therapy, which condition cognitive disorders that are eligible for specialised psycho-pedagogical intervention.

The ecological executive function of epileptic children with ADHD%癫痫共患ADHD儿童的生态学执行功能

Institute of Scientific and Technical Information of China (English)

陈静; 周农; 刘天龙; 顾安丽; 陈晓霞

2015-01-01

Objective To study the characteristics of ecological executive function and influencing factors of epilep-tic children with attention deficit hyperactivity disorder ( ADHD) . Methods By utilizing the cross-sectional survey study, 79 cases of epileptic children were evaluated according to the clinical diagnostic scale of the Diagnostic and Statistical Manual of Mental Disorders ( DSM-IV, USA);all of the epileptic children and 52 cases of normal chil-dren with the matched age, gender and levels of education were completed with the questionnaire evaluation of Be-havior Rating Index of Executive Function ( BRIEF, Parents Version) . Results ①30 cases of ADHD were found in 79 cases of children with epilepsy, and the coincidence rate was 37. 97%. There were no statistically significant differences between epileptic children with ADHD and epileptic children without ADHD in gender, age, onset age, education level , course of diseases , control or not , family history and history of traumatic brain injuries . But there were statistically significant differences in epileptic seizure type and drug treatment or not ( P<0. 05 ) . ②The two scores of behavior management index and metacognition were higher in epileptic children with ADHD than the epi-leptic children without ADHD and the normal group, and the differences were statistically significant (P<0. 05).③ The clinical characteristics of seizure type, course of disease, epileptic seizure control or not and drug treatment or not in epileptic children with ADHD were significantly correlated with BRIEF(P<0. 05). Conclusion The eco-logical executive function is comprehensively damaged in the epileptic children with ADHD, and the damage is more serious than the epileptic children without ADHD. The ecological executive function of epileptic children with ADHD is significantly influenced by epilepsy seizure type, epilepsy control or not and drug treatment or not.%目的 探讨癫痫共患注意缺陷多动障碍( ADHD

Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease.

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Gunay, Mine Silindir; Ozer, A Yekta; Chalon, Sylvie

2016-01-01

Although a variety of therapeutic approaches are available for the treatment of Parkinson's disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson's disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α -synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson's disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson's Disease therapy and reduce its side effects.

Cortical GABAergic excitation contributes to epileptic activities around human glioma

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Pallud, Johan; Varlet, Pascale; Cresto, Noemie; Baulac, Michel; Duyckaerts, Charles; Kourdougli, Nazim; Chazal, Geneviève; Devaux, Bertrand; Rivera, Claudio; Miles, Richard; Capelle, Laurent; Huberfeld, Gilles

2015-01-01

Rationale Diffuse brain gliomas induce seizures in a majority of patients. As in most epileptic disorders, excitatory glutamatergic mechanisms are involved in the generation of epileptic activities in the neocortex surrounding gliomas. However, chloride homeostasis is known to be perturbed in glial tumor cells. Thus the contribution of GABAergic mechanisms which depend on intracellular chloride and which are defective or pro-epileptic in other structural epilepsies merits closer study. Objective We studied in neocortical slices from the peritumoral security margin resected around human brain gliomas, the occurrence, networks, cells and signaling basis of epileptic activities. Results Postoperative glioma tissue from 69% of patients spontaneously generated interictal-like discharges. These events were synchronized, with a high frequency oscillation signature, in superficial layers of neocortex around glioma areas with tumor infiltration. Interictal-like events depended on both glutamatergic transmission and on depolarizing GABAergic signaling. About 65% of pyramidal cells were depolarized by GABA released by interneurons. This effect was related to perturbations in Chloride homeostasis, due to changes in expression of chloride co-transporters: KCC2 was reduced and expression of NKCC1 increased. Ictal-like activities were initiated by convulsant stimuli exclusively in these epileptogenic areas. Conclusions Epileptic activities are sustained by excitatory effects of GABA in the peritumoral human neocortex, as in temporal lobe epilepsies. Glutamate and GABA signaling are involved in oncogenesis and chloride homeostasis is perturbed. These same factors, induce an imbalance between synaptic excitatory and inhibition underly epileptic discharges in tumor patients. PMID:25009229

Consciousness in non-epileptic attack disorder.

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Reuber, Markus; Kurthen, M

2011-01-01

Non-epileptic attack disorder (NEAD) is one of the most important differential diagnoses of epilepsy. Impairment of consciousness is the key feature of non-epileptic attacks (NEAs). The first half of this review summarises the clinical research literature featuring observations relating to consciousness in NEAD. The second half places this evidence in the wider context of the recent discourse on consciousness in neuroscience and the philosophy of mind. We argue that studies of consciousness should not only distinguish between the 'level' and `content' of consciousness but also between 'phenomenal consciousness' (consciousness of states it somehow "feels to be like") and 'access consciousness' (having certain 'higher' cognitive processes at one's disposal). The existing evidence shows that there is a great intra- and interindividual variability of NEA experience. However, in most NEAs phenomenal experience - and, as a precondition for that experience, vigilance or wakefulness - is reduced to a lesser degree than in those epileptic seizures involving impairment of consciousness. In fact, complete loss of "consciousness" is the exception rather than the rule in NEAs. Patients, as well as external observers, may have a tendency to overestimate impairments of consciousness during the seizures.

FT-Raman, FT-IR and UV-visible spectral investigations and ab initio computations of anti-epileptic drug: vigabatrin.

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Edwin, Bismi; Joe, I Hubert

2013-10-01

Vibrational analysis of anti-epileptic drug vigabatrin, a structural GABA analog was carried out using NIR FT-Raman and FTIR spectroscopic techniques. The equilibrium geometry, various bonding features and harmonic vibrational wavenumbers were studied using density functional theory method. The detailed interpretation of the vibrational spectra has been carried out with the aid of VEDA.4 program. Vibrational spectra, natural bond orbital analysis and optimized molecular structure show clear evidence for the effect of electron charge transfer on the activity of the molecule. Predicted electronic absorption spectrum from TD-DFT calculation has been compared with the UV-vis spectrum. The Mulliken population analysis on atomic charges and the HOMO-LUMO energy were also calculated. Good consistency is found between the calculated results and experimental data for the electronic absorption as well as IR and Raman spectra. The blue-shifting of the C-C stretching wavenumber reveals that the vinyl group is actively involved in the conjugation path. The NBO analysis confirms the occurrence of intramolecular hyperconjugative interactions resulting in ICT causing stabilization of the system. Copyright © 2013 Elsevier B.V. All rights reserved.

Wavelet analysis of epileptic spikes

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Latka, Miroslaw; Was, Ziemowit; Kozik, Andrzej; West, Bruce J.

2003-05-01

Interictal spikes and sharp waves in human EEG are characteristic signatures of epilepsy. These potentials originate as a result of synchronous pathological discharge of many neurons. The reliable detection of such potentials has been the long standing problem in EEG analysis, especially after long-term monitoring became common in investigation of epileptic patients. The traditional definition of a spike is based on its amplitude, duration, sharpness, and emergence from its background. However, spike detection systems built solely around this definition are not reliable due to the presence of numerous transients and artifacts. We use wavelet transform to analyze the properties of EEG manifestations of epilepsy. We demonstrate that the behavior of wavelet transform of epileptic spikes across scales can constitute the foundation of a relatively simple yet effective detection algorithm.

Wavelet analysis of epileptic spikes

CERN Document Server

Latka, M; Kozik, A; West, B J; Latka, Miroslaw; Was, Ziemowit; Kozik, Andrzej; West, Bruce J.

2003-01-01

Interictal spikes and sharp waves in human EEG are characteristic signatures of epilepsy. These potentials originate as a result of synchronous, pathological discharge of many neurons. The reliable detection of such potentials has been the long standing problem in EEG analysis, especially after long-term monitoring became common in investigation of epileptic patients. The traditional definition of a spike is based on its amplitude, duration, sharpness, and emergence from its background. However, spike detection systems built solely around this definition are not reliable due to the presence of numerous transients and artifacts. We use wavelet transform to analyze the properties of EEG manifestations of epilepsy. We demonstrate that the behavior of wavelet transform of epileptic spikes across scales can constitute the foundation of a relatively simple yet effective detection algorithm.

Clinical management of drug-drug interactions in HCV therapy: Challenges and solutions

NARCIS (Netherlands)

Burger, D.M.; Back, D.; Buggisch, P.; Buti, M.; Craxi, A.; Foster, G.; Klinker, H.; Larrey, D.; Nikitin, I.; Pol, S. van der; Puoti, M.; Romero-Gomez, M.; Wedemeyer, H.; Zeuzem, S.

2013-01-01

Hepatitis C virus (HCV) infected patients often take multiple co-medications to treat adverse events related to HCV therapy, or to manage other co-morbidities. Drug-drug interactions associated with this polypharmacy are relatively new to the field of HCV pharmacotherapy. With the advent of the

Drug therapy in patients with Parkinson’s disease

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Müller Thomas

2012-05-01

Full Text Available Abstract Parkinson`s disease (PD is a progressive, disabling neurodegenerative disorder with onset of motor and non-motor features. Both reduce quality of life of PD patients and cause caregiver burden. This review aims to provide a survey of possible therapeutic options for treatment of motor and non motor symptoms of PD and to discuss their relation to each other. MAO-B-Inhibitors, NMDA antagonists, dopamine agonists and levodopa with its various application modes mainly improve the dopamine associated motor symptoms in PD. This armentarium of PD drugs only partially influences the onset and occurrence of non motor symptoms. These PD features predominantly result from non dopaminergic neurodegeneration. Autonomic features, such as seborrhea, hyperhidrosis, orthostatic syndrome, salivation, bladder dysfunction, gastrointestinal disturbances, and neuropsychiatric symptoms, such as depression, sleep disorders, psychosis, cognitive dysfunction with impaired execution and impulse control may appear. Drug therapy of these non motor symptoms complicates long-term PD drug therapy due to possible occurrence of drug interactions, - side effects, and altered pharmacokinetic behaviour of applied compounds. Dopamine substituting compounds themselves may contribute to onset of these non motor symptoms. This complicates the differentiation from the disease process itself and influences therapeutic options, which are often limited because of additional morbidity with necessary concomitant drug therapy.

Population pharmacokinetic analysis for 10-monohydroxy derivative of oxcarbazepine in pediatric epileptic patients shows no difference between Japanese and other ethnicities.

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Sugiyama, Ikuo; Bouillon, Thomas; Yamaguchi, Masayuki; Suzuki, Hikoe; Hirota, Takashi; Fink, Martin

2015-04-01

Oxcarbazepine is an anti-epileptic drug, which is almost completely metabolized by cytosolic enzymes in the liver to the active 10-monohyroxy metabolite (MHD) following oral administration. The pharmacokinetic (PK) profiles of MHD were evaluated in pediatric epileptic patients and a possible ethnic difference in PK of MHD between Japanese and non-Japanese pediatric patients was assessed. A non-linear mixed effect modeling approach was used to determine the PK of MHD. A one-compartment population model with first-order absorption appropriately described the PK of MHD. No clinically relevant differences were found for using body surface area or weight to explain between-patient variability, therefore the final model included the effects of body weight on apparent clearance (CL/F) and apparent volume of distribution (V/F) of MHD, and in addition, the effect of 3 concomitant anti-epileptic drugs (carbamazepine, phenobarbital and phenytoin) on CL/F of MHD. Inclusion of ethnicity as a covariate in the final model, concluded no ethnic difference with respect to CL/F of MHD between Japanese and non-Japanese patients. Hence, oxcarbazepine can be generally applied using the same dosage and administration for the treatment of partial onset seizures in pediatric patients, regardless of ethnicity. Copyright © 2014 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Epileptic seizures and headache/migraine: a review of types of association and terminology.

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Cianchetti, Carlo; Pruna, Dario; Ledda, Mariagiuseppina

2013-11-01

There are different possible temporal associations between epileptic seizures and headache attacks which have given rise to unclear or controversial terminologies. The classification of the International League Against Epilepsy does not refer to this type of disorder, while the International Classification of Headache Disorders (ICHD-2) defines three kinds of association: (1) migraine-triggered seizure ("migralepsy"), (2) hemicrania epileptica, and (3) post-ictal headache. We performed an extensive review of the literature, not including "post-ictal" and "inter-ictal" headaches. On the basis of well-documented reports, the following clinical entities may be identified: (A) "epileptic headache (EH)" or "ictal epileptic headache (IEH)": in this condition headache (with or without migrainous features) is an epileptic manifestation per se, with onset, and cessation if isolated, coinciding with the scalp or deep EEG pattern of an epileptic seizure. EH maybe followed by other epileptic manifestations (motor/sensory/autonomic); this condition should be differentiated from "pure" or "isolated" EH, in which headache/migraine is the sole epileptic manifestation (requiring differential diagnosis from other headache forms). "Hemicrania epileptica" (if confirmed) is a very rare variant of EH, characterized by ipsilateral location of headache and ictal EEG paroxysms. (B) "Pre-ictal migraine" and "pre-ictal headache": when a headache attack is followed during, or shortly after, by a typical epileptic seizure. The migraine attack may be with or without aura, and its seizure-triggering role ("migraine-triggered seizure") is still a subject of debate. A differentiation from occipital epilepsy is mandatory. The term "migralepsy" has not been used uniformly, and may therefore led to misinterpretation. On the basis of this review we suggest definitions and a terminology which may become the basis of a forthcoming classification of headaches associated with epileptic seizures. Copyright

Reflex epileptic mechanisms in humans: Lessons about natural ictogenesis.

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Wolf, Peter

2017-06-01

The definition of reflex epileptic seizures is that specific seizure types can be triggered by certain sensory or cognitive stimuli. Simple triggers are sensory (most often visual, more rarely tactile or proprioceptive; simple audiogenic triggers in humans are practically nonexistent) and act within seconds, whereas complex triggers like praxis, reading and talking, and music are mostly cognitive and work within minutes. The constant relation between a qualitatively, often even quantitatively, well-defined stimulus and a specific epileptic response provides unique possibilities to investigate seizure generation in natural human epilepsies. For several reflex epileptic mechanisms (REMs), this has been done. Reflex epileptic mechanisms have been reported less often in focal lesional epilepsies than in idiopathic "generalized" epilepsies (IGEs) which are primarily genetically determined. The key syndrome of IGE is juvenile myoclonic epilepsy (JME), where more than half of the patients present reflex epileptic traits (photosensitivity, eye closure sensitivity, praxis induction, and language-induced orofacial reflex myocloni). Findings with multimodal investigations of cerebral function concur to indicate that ictogenic mechanisms in IGEs largely (ab)use preexisting functional anatomic networks (CNS subsystems) normally serving highly complex physiological functions (e.g., deliberate complex actions and linguistic communication) which supports the concept of system epilepsy. Whereas REMs in IGEs, thus, are primarily function-related, in focal epilepsies, they are primarily localization-related. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic". Copyright © 2015 Elsevier Inc. All rights reserved.

Targeted drugs in radiation therapy

International Nuclear Information System (INIS)

Favaudon, V.; Hennequin, C.; Hennequin, C.

2004-01-01

New drugs aiming at the development of targeted therapies have been assayed in combination with ionizing radiation over the past few years. The rationale of this concept comes from the fact that the cytotoxic potential of targeted drugs is limited, thus requiring concomitant association with a cytotoxic agent for the eradication of tumor cells. Conversely a low level of cumulative toxicity is expected from targeted drugs. Most targeted drugs act through inhibition of post-translational modifications of proteins, such as dimerization of growth factor receptors, prenylation reactions, or phosphorylation of tyrosine or serine-threonine residues. Many systems involving the proteasome, neo-angiogenesis promoters, TGF-β, cyclooxygenase or the transcription factor NF-κB, are currently under investigation in hopes they will allow a control of cell proliferation, apoptosis, cell cycle progression, tumor angiogenesis and inflammation. A few drugs have demonstrated an antitumor potential in particular phenotypes. In most instances, however, radiation-drug interactions proved to be strictly additive in terms of cell growth inhibition or induced cell death. Strong potentiation of the response to radiotherapy is expected to require interaction with DNA repair mechanisms. (authors)

[Consensus clinical practice guidelines of the Andalusian Epilepsy Society: therapeutic recommendations when dealing with a first epileptic seizure and in epileptic status].

Science.gov (United States)

Mercadé-Cerda, J M; Sánchez-Alvarez, J C; Galán-Barranco, J M; Moreno-Alegre, V; Serrano-Castro, P J; Cañadillas-Hidalgo, F M

Most epileptic seizures are brief and self-limiting, but sometimes they can last longer than expected and this entails (in the case of generalised seizures) a high risk of morbidity and mortality, which increases as they get longer. This severity justifies the need to draw up a set of consensus-based practice guidelines based on implicit evidence, to use Liberati's nomenclature, concerning aspects related to the recommended therapeutic management of a patient with prolonged seizures who is being attended in an emergency department. A selective search was conducted on PubMed-Medline for scientific information related to the subject using scientific evidence filters. This search was completed in other scientific evidence search engines, such as Tripdatabase, Biblioteca Cochrane Plus or DARE. The selected references were analysed and discussed by the authors, and the available evidence and any recommendations that could be drawn from it were collected. The search revealed the existence of 33 primary documents and six practice guidelines or protocols related with the topic under study. The recommendations were inserted in the text explicitly. The therapeutic protocol must be started when faced with any seizures that last more than five minutes. First, steps must be taken to ensure proper respiratory and cardiocirculatory functioning, and then fast-acting antiepileptic drugs are administered intravenously and in high doses until the cause is identified and controlled. Due to their lower level of morbidity and mortality, prolonged non-convulsive seizures do not generally require therapy that is so vigorous and with such a high risk of complications.

Imaging DC MEG Fields Associated with Epileptic Onset

Science.gov (United States)

Weiland, B. J.; Bowyer, S. M.; Moran, J. E.; Jenrow, K.; Tepley, N.

2004-10-01

Magnetoencephalography (MEG) is a non-invasive brain imaging modality, with high spatial and temporal resolution, used to evaluate and quantify the magnetic fields associated with neuronal activity. Complex partial epileptic seizures are characterized by hypersynchronous neuronal activity believed to arise from a zone of epileptogenesis. This study investigated the characteristics of direct current (DC) MEG shifts arising at epileptic onset. MEG data were acquired with rats using a six-channel first order gradiometer system. Limbic status epilepticus was induced by IA (femoral) administration of kainic acid. DC-MEG shifts were observed at the onset of epileptic spike train activity and status epilepticus. Epilepsy is also being studied in patients undergoing presurgical mapping from the Comprehensive Epilepsy Center at Henry Ford Hospital using a whole head Neuromagnetometer. Preliminary data analysis shows that DC-MEG waveforms, qualitatively similar to those seen in the animal model, are evident prior to seizure activity in human subjects.

Alternative Drugs in Pain Therapy

Directory of Open Access Journals (Sweden)

İlker Kelle

2006-01-01

Full Text Available Various treatment modalities of acute and chronic pain have been an area of interest of medicine and investigators for centuries. There are two major classes of drugs that are used to control pain: opioid and non-opioid analgesics. They could be used in the case of monotherapy or combination therapy in pain management. However, these agents are not accepted as ideal drugs in clinical approaches against pain because of their serious side effects such as development of tolerance and addiction, renal failure and gastrointestinal bleeding. As a consequent, developing new forms of pain relievers that are more safe and effective without any other side effects has became the main goal of researchers. In recent studies, it has been shown that conotoxin therapies are not addictive, and have tolerable indexes unlike opioids. In addition, conotoxins side effects are much milder and easier to manage than those of opioids. In this regard, it has been emphasized that biotoxins such as conotoxins obtained from marine creatures can be better choices in pain management for future prospects.

Basic Mechanisms of Action of the Antiepileptic Drugs

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Kuzmanova R.

2017-10-01

Full Text Available Available antiepileptic drugs interact with a variety of different molecular targets. The mechanism of action of most anticonvulsants is most often complex with a number of affected regions. The combination of mechanisms of action of drugs in particular proportions can possibly determine the showcase of its antiepileptic activity. The common factor between the different supposed mechanisms for a number of drugs includes the possibility for modulating the excitatory and inhibitory neurotransmission through effects upon the voltage-gated ion channels, synaptic plasticity, heterogeneous receptors, and metabolism of neurotransmitters. There are controversial data on the extent to which a specific action can be the reason for the wholesome anticonvulsive characteristics of various medications, as well as the relation with the presence of undesired drug effects. The complexity of the action of some antiepileptic drugs creates conditions for optimal choice during therapy. In many cases, the insufficient familiarity with individual genetic differences and the disease related receptor damages can hinder defining a particular drug action. Characterizing the mechanisms of action of the present antiepileptic medications would increase the understanding for the pathophysiological mechanisms of epileptic seizures, as well as the development of new therapeutic strategies. The development of novel antiepileptic drugs and the ongoing research regarding the mechanism of action of established antiepileptic drugs, are continuously increasing the level of complexity in the spectrum of molecular targets relevant for epilepsy therapy. The current state of knowledge as well as the limitations in our understanding should guide future research aiming for a more detailed elucidation of the impact of genetics and pathophysiological mechanisms on interindividual differences in expression and function of antiepileptic drug targets.

DNA nanostructure-based drug delivery nanosystems in cancer therapy.

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Wu, Dandan; Wang, Lei; Li, Wei; Xu, Xiaowen; Jiang, Wei

2017-11-25

DNA as a novel biomaterial can be used to fabricate different kinds of DNA nanostructures based on its principle of GC/AT complementary base pairing. Studies have shown that DNA nanostructure is a nice drug carrier to overcome big obstacles existing in cancer therapy such as systemic toxicity and unsatisfied drug efficacy. Thus, different types of DNA nanostructure-based drug delivery nanosystems have been designed in cancer therapy. To improve treating efficacy, they are also developed into more functional drug delivery nanosystems. In recent years, some important progresses have been made. The objective of this review is to make a retrospect and summary about these different kinds of DNA nanostructure-based drug delivery nanosystems and their latest progresses: (1) active targeting; (2) mutidrug co-delivery; (3) construction of stimuli-responsive/intelligent nanosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

MDR-1 and MRP2 gene polymorphisms in Mexican epileptic pediatric patients with complex partial seizures.

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David eEscalante-Santiago

2014-10-01

Full Text Available Although the Pgp efflux transport protein is overexpressed in resected tissue of patients with epilepsy, the presence of polymorphisms in MDR1 / ABCB1 and MRP2 / ABCC2 in patients with antiepileptic-drugs resistant epilepsy is controversial. The aim of this study was to perform an exploratory study to identify nucleotide changes and search new and reported mutations in patients with antiepileptic-drugs resistant epilepsy (ADR and patients with good response to anti-epileptic drugs (CTR in a rigorously selected population. We analyzed 22 samples from drug-resistant patients with epilepsy and 7 samples from patients with good response to anti-epileptic drugs. Genomic DNA was obtained from leukocytes. Eleven exons in both genes were genotyped. The concentration of drugs in saliva and plasma was determined. The concentration of valproic acid in saliva was lower in ADR than in CRT. In ABCB1, five reported SNPs and five unreported nucleotide changes were identified; rs2229109 (GA and rs2032582 (AT and AG were found only in the ADR. Of six SNPs associated with the ABCC2 that were found in the study population, rs3740066 (TT and 66744T>A (TG were found only in the ADR. The strongest risk factor in the ABCB1 gene was identified as the TA genotype of rs2032582, whereas for the ABCC2 gene the strongest risk factor was the T allele of rs3740066. The screening of SNPs in ACBC1 and ABCC2 indicates that the Mexican patients with epilepsy in this study display frequently reported ABCC1 polymorphisms; however, in the study subjects with a higher risk factor for drug resistance, new nucleotide changes were found in the ABCC2 gene. Thus, the population of Mexican patients with AED-resistant epilepsy used in this study exhibits genetic variability with respect to those reported in other study populations; however, it is necessary to explore this polymorphism in a larger population of patients with AED-resistant epilepsy.

Psycho-Social Aspects of Educating Epileptic Children: Roles for School Psychologists.

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Frank, Brenda B.

1985-01-01

Epileptic children may have physical and emotional needs which can interfere with learning and socialization. Current prevalence estimates, definitions, and classifications of epilepsy are surveyed. Factors affecting the epileptic child's school performance and specific learning problems are addressed. Specific roles are presented for school…

Drug-drug interactions between anti-retroviral therapies and drugs of abuse in HIV systems.

Science.gov (United States)

Kumar, Santosh; Rao, P S S; Earla, Ravindra; Kumar, Anil

2015-03-01

Substance abuse is a common problem among HIV-infected individuals. Importantly, addictions as well as moderate use of alcohol, smoking, or other illicit drugs have been identified as major reasons for non-adherence to antiretroviral therapy (ART) among HIV patients. The literature also suggests a decrease in the response to ART among HIV patients who use these substances, leading to failure to achieve optimal virological response and increased disease progression. This review discusses the challenges with adherence to ART as well as observed drug interactions and known toxicities with major drugs of abuse, such as alcohol, smoking, methamphetamine, cocaine, marijuana, and opioids. The lack of adherence and drug interactions potentially lead to decreased efficacy of ART drugs and increased ART, and drugs of abuse-mediated toxicity. As CYP is the common pathway in metabolizing both ART and drugs of abuse, we discuss the possible involvement of CYP pathways in such drug interactions. We acknowledge that further studies focusing on common metabolic pathways involving CYP and advance research in this area would help to potentially develop novel/alternate interventions and drug dose/regimen adjustments to improve medication outcomes in HIV patients who consume drugs of abuse.

Does rapid and physiological astrocyte–neuron signalling amplify epileptic activity?

Science.gov (United States)

2016-01-01

Abstract The hippocampus is a key brain region in the pathophysiology of mesial temporal lobe epilepsy. Long‐term changes of its architecture and function on the network and cellular level are well documented in epilepsy. Astrocytes can control many aspects of neuronal function and their long‐term alterations over weeks, months and years play an important role in epilepsy. However, a pathophysiological transformation of astrocytes does not seem to be required for astrocytes to contribute to epileptic activity. Some of the properties of physiological astrocyte–neuron communication could allow these cells to exacerbate or synchronize neuronal firing on shorter time scales of milliseconds to minutes. Therefore, these astrocyte–neuron interactions are increasingly recognized as potential contributors to epileptic activity. Fast and reciprocal communication between astrocytes and neurons is enabled by a diverse set of mechanisms that could both amplify and counteract epileptic activity. They may thus promote or cause development of epileptic activity or inhibit it. Mechanisms of astrocyte–neuron interactions that can quickly increase network excitability involve, for example, astrocyte Ca2+ and Na+ signalling, K+ buffering, gap junction coupling and metabolism. However, rapid changes of astrocyte neurotransmitter uptake and morphology may also underlie or support development of network hyperexcitability. The temporal characteristics of these interactions, their ability to synchronize neuronal activity and their net effect on network activity will determine their contribution to the emergence or maintenance of epileptic activity. PMID:27106234

Does rapid and physiological astrocyte-neuron signalling amplify epileptic activity?

Science.gov (United States)

Henneberger, Christian

2017-03-15

The hippocampus is a key brain region in the pathophysiology of mesial temporal lobe epilepsy. Long-term changes of its architecture and function on the network and cellular level are well documented in epilepsy. Astrocytes can control many aspects of neuronal function and their long-term alterations over weeks, months and years play an important role in epilepsy. However, a pathophysiological transformation of astrocytes does not seem to be required for astrocytes to contribute to epileptic activity. Some of the properties of physiological astrocyte-neuron communication could allow these cells to exacerbate or synchronize neuronal firing on shorter time scales of milliseconds to minutes. Therefore, these astrocyte-neuron interactions are increasingly recognized as potential contributors to epileptic activity. Fast and reciprocal communication between astrocytes and neurons is enabled by a diverse set of mechanisms that could both amplify and counteract epileptic activity. They may thus promote or cause development of epileptic activity or inhibit it. Mechanisms of astrocyte-neuron interactions that can quickly increase network excitability involve, for example, astrocyte Ca 2+ and Na + signalling, K + buffering, gap junction coupling and metabolism. However, rapid changes of astrocyte neurotransmitter uptake and morphology may also underlie or support development of network hyperexcitability. The temporal characteristics of these interactions, their ability to synchronize neuronal activity and their net effect on network activity will determine their contribution to the emergence or maintenance of epileptic activity. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Effect of epileptic seizures on the cerebrospinal fluid--A systematic retrospective analysis.

Science.gov (United States)

Tumani, Hayrettin; Jobs, Catherine; Brettschneider, Johannes; Hoppner, Anselm C; Kerling, Frank; Fauser, Susanne

2015-08-01

Analyses of the cerebrospinal fluid (CSF) are obligatory when epileptic seizures manifest for the first time in order to exclude life-threatening causes or treatable diseases such as acute infections or autoimmune encephalitis. However, there are only few systematic investigations on the effect of seizures themselves on CSF parameters and the significance of these parameters in differential diagnosis. CSF samples of 309 patients with epileptic and 10 with psychogenic seizures were retrospectively analyzed. CSF samples were collected between 1999 and 2008. Cell counts, the albumin quotient, lactate and Tau-protein levels were determined. Findings were correlated with seizure types, seizure etiology (symptomatic, cryptogenic, occasional seizure), and seizure duration. Pathological findings were only observed in patients with epileptic but not with psychogenic seizures. The lactate concentration was elevated in 14%, the albumin quotient in 34%, and the Tau protein level in 36% of CSF samples. Cell counts were only slightly elevated in 6% of patients. Different seizure types influenced all parameters except for the cell count: In status epilepticus highest, in simple partial seizures lowest values were seen. Symptomatic partial and generalized epileptic seizures had significantly higher Tau-protein levels than cryptogenic partial seizures. In patients with repetitive and occasional epileptic seizures, higher Tau-protein levels were seen than in those with psychogenic seizures. Duration of epileptic seizures was positively correlated with the albumin quotient, lactate and Tau-protein levels. High variability of investigated CSF parameters within each subgroup rendered a clear separation between epileptic and psychogenic seizures impossible. Elevated cell counts are infrequently observed in patients with epileptic seizures and should therefore not uncritically be interpreted as a postictal phenomenon. However, blood-CSF barrier disruption, increased glucose metabolism

Drug Therapy Problems in Patients on Antihypertensives and ...

African Journals Online (AJOL)

Drug therapy problems (DTPs), with the associated risks inherent in antihypertensive and antidiabetic therapy require utmost attention. This present study was aimed at assessing the DTPs observed in the management of hypertension and diabetes mellitus (DM) in two tertiary health facilities in Niger Delta region. In this ...

Smart Drug Delivery Systems in Cancer Therapy.

Science.gov (United States)

Unsoy, Gozde; Gunduz, Ufuk

2018-02-08

Smart nanocarriers have been designed for tissue-specific targeted drug delivery, sustained or triggered drug release and co-delivery of synergistic drug combinations to develop safer and more efficient therapeutics. Advances in drug delivery systems provide reduced side effects, longer circulation half-life and improved pharmacokinetics. Smart drug delivery systems have been achieved successfully in the case of cancer. These nanocarriers can serve as an intelligent system by considering the differences of tumor microenvironment from healthy tissue, such as low pH, low oxygen level, or high enzymatic activity of matrix metalloproteinases. The performance of anti-cancer agents used in cancer diagnosis and therapy is improved by enhanced cellular internalization of smart nanocarriers and controlled drug release. Here, we review targeting, cellular internalization; controlled drug release and toxicity of smart drug delivery systems. We are also emphasizing the stimulus responsive controlled drug release from smart nanocarriers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Brand-name drug, generic drug, orphan drug. Pharmacological therapy with biosimilar drugs - provision of due diligence in the treatment process.

Science.gov (United States)

Zajdel, Justyna; Zajdel, Radosław

2013-01-01

Due diligence in the process of provision of healthcare services refers, among other elements, to the application of pharmacological therapy at a time which offers the greatest chance for a successful outcome of treatment, i.e. for achieving the optimum expected effect understood as an improvement in the patient's health, reduction of health risks or elimination of the disease. However, due diligence may also refer to actions aimed at ensuring that neither the patient nor the healthcare payer is required to incur unreasonable costs in the process of treatment. The validity of that statement stems not only from normative acts but also from ethical standards laid down in the Medical Code of Ethics (Article 57 section 2). It often happens that the provision of optimal treatment calls for deviations from the formal provisions included in Summary Product Characteristics (SPCs), and the application of drugs that are bioequivalent to reference drugs, which translates into a significant reduction of costs. The present study addresses the problem of acceptability of a specific form of drug substitution consisting in the replacement of a reference drug with a generic drug. Also explored are legal aspects associated with the possibility of therapy based on "off-label use". The study reviews normative acts existing in the Polish and EU legislation. It also provides a clear definition of orphan drug, which has made it possible to make a distinction and investigate mutual relations between the concepts of brand-name (reference) drug, orphan drug and generic drug.

Antiretroviral drug resistance in HIV-1 therapy-naive patients in Cuba.

Science.gov (United States)

Pérez, Lissette; Kourí, Vivian; Alemán, Yoan; Abrahantes, Yeisel; Correa, Consuelo; Aragonés, Carlos; Martínez, Orlando; Pérez, Jorge; Fonseca, Carlos; Campos, Jorge; Álvarez, Delmis; Schrooten, Yoeri; Dekeersmaeker, Nathalie; Imbrechts, Stijn; Beheydt, Gertjan; Vinken, Lore; Soto, Yudira; Álvarez, Alina; Vandamme, Anne-Mieke; Van Laethem, Kristel

2013-06-01

In Cuba, antiretroviral therapy rollout started in 2001 and antiretroviral therapy coverage has reached almost 40% since then. The objectives of this study were therefore to analyze subtype distribution, and level and patterns of drug resistance in therapy-naive HIV-1 patients. Four hundred and one plasma samples were collected from HIV-1 therapy-naive patients in 2003 and in 2007-2011. HIV-1 drug resistance genotyping was performed in the pol gene and drug resistance was interpreted according to the WHO surveillance drug-resistance mutations list, version 2009. Potential impact on first-line therapy response was estimated using genotypic drug resistance interpretation systems HIVdb version 6.2.0 and Rega version 8.0.2. Phylogenetic analysis was performed using Neighbor-Joining. The majority of patients were male (84.5%), men who have sex with men (78.1%) and from Havana City (73.6%). Subtype B was the most prevalent subtype (39.3%), followed by CRF20-23-24_BG (19.5%), CRF19_cpx (18.0%) and CRF18_cpx (10.3%). Overall, 29 patients (7.2%) had evidence of drug resistance, with 4.0% (CI 1.6%-4.8%) in 2003 versus 12.5% (CI 7.2%-14.5%) in 2007-2011. A significant increase in drug resistance was observed in recently HIV-1 diagnosed patients, i.e. 14.8% (CI 8.0%-17.0%) in 2007-2011 versus 3.8% (CI 0.9%-4.7%) in 2003 (OR 3.9, CI 1.5-17.0, p=0.02). The majority of drug resistance was restricted to a single drug class (75.8%), with 55.2% patients displaying nucleoside reverse transcriptase inhibitor (NRTI), 10.3% non-NRTI (NNRTI) and 10.3% protease inhibitor (PI) resistance mutations. Respectively, 20.7% and 3.4% patients carried viruses containing drug resistance mutations against NRTI+NNRTI and NRTI+NNRTI+PI. The first cases of resistance towards other drug classes than NRTI were only detected from 2008 onwards. The most frequent resistance mutations were T215Y/rev (44.8%), M41L (31.0%), M184V (17.2%) and K103N (13.8%). The median genotypic susceptibility score for the

Bone scintigraphy during therapy with cytostatically acting drugs

International Nuclear Information System (INIS)

Schmidt, U.; Pries, H.H.; Joseph, K.; Mahlstedt, J.; Marburg Univ.

1976-01-01

Case reports show up, that bone scintigraphy during therapy of metastasing cancer of mamma or prostata with cytostatically acting drugs may reveal 'pseudonormal' results. False negative diagnosis can be excluded only by carefully regarding drug history. Gamma-camera with wholebody scan device for scintigraphy in two projections simplifies safe evaluation significantly. (orig.) [de

Oral hygiene practices and status of epileptics and controls in Lagos ...

African Journals Online (AJOL)

Bacterial plaque is the primary aetiologic agent in inflammatory periodontal disease. This study therefore aims to investigate the oral health practices and status of epileptics and controls. This will form the basis of a more detailed study on the periodontal status and treatment needs of epileptic patients. Materials and Method: ...

Epileptic seizures in patients with a posterior circulation infarct

Directory of Open Access Journals (Sweden)

Yüksel Kaplan

2014-08-01

Full Text Available OBJECTIVE: The aim of this study was to investigate the frequency of seizures and the clinical features of patients with seizures related to a posterior circulation infarct (POCI. METHODS: We reviewed all ischemic stroke patients admitted to our clinic between January 2011 and January 2012. The patients’ database information was retrospectively analyzed. Fifty-five patients with a POCI were included in the study. We reviewed all patients with epileptic seizures related to a POCI. Age, gender, recurrent stroke, risk factors, etiology, radiographic localization, the seizure type and onset time, and the electroencephalographic findings of patients were evaluated. We excluded all patients who had precipitating conditions during seizures such as taking drugs, acid-base disturbances, electrolyte imbalance, and history of epilepsy. RESULTS: Seizures were observed in four patients (3 male, 1 female with a POCI related epileptic seizures (7.2%. The etiology of strokes was cardiac-embolic in 3 patients and vertebral artery dissection in 1 patient. Seizures occurred in 2 patients as presenting finding, in 1 patient within 7 days, and 1 patient within 28 days. Primary generalized tonic-clonic seizures occurred in 3 patients and simple partial seizures with secondary generalization in 1 patient. Three patients had cerebellum infarction at the left hemisphere. One patient had lateral medullary infarction at the right side. The electroencephalographic findings of patients were normal. CONCLUSION: Studies involving patients with seizures related to a POCI are novel and few in number. Three patients with seizure had cerebellum infarction. The cerebellum in these patients may contribute via different mechanisms over seizure activity.

EFFICACY OF RUFINAMIDE IN THE TREATMENT OF DRUG-RESISTANT FOCAL EPILEPSIES IN PAEDIATRIC PRACTICE

Directory of Open Access Journals (Sweden)

I. O. Shchederkina

2016-01-01

Full Text Available Among drug-resistant epilepsies, epileptic syndromes, characterized by combination of several types of seizures, are considered to be the most difficult in terms of treatment. Lennox–Gastaut syndrome is one of them. It manifests with polymorphic seizures (tonic axial, myatonic, atypical absence seizures, status epilepticus of minor motor seizures, myoclonic, generalized convulsive, and focal seizures. This is a heterogeneous disease, represented by a complex of clinical and electroencephalographic manifestations with various etiology. Current review is devoted to a novel antiepileptic drug rufinamide, which has a new mechanism of action. The drug has been registered in Russia in 2015. The authors also describe their own experience of rufinamide usage in the treatment of drug-resistant focal epilepsy as a part of multicomponent therapy for polymorphic seizures. One patient achieved clinical remission for 16 months; the second one had more than 50 % decrease in seizures frequency with a remission of drop-attacks.

Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance.

Science.gov (United States)

Khdair, Ayman; Chen, Di; Patil, Yogesh; Ma, Linan; Dou, Q Ping; Shekhar, Malathy P V; Panyam, Jayanth

2010-01-25

Tumor drug resistance significantly limits the success of chemotherapy in the clinic. Tumor cells utilize multiple mechanisms to prevent the accumulation of anticancer drugs at their intracellular site of action. In this study, we investigated the anticancer efficacy of doxorubicin in combination with photodynamic therapy using methylene blue in a drug-resistant mouse tumor model. Surfactant-polymer hybrid nanoparticles formulated using an anionic surfactant, Aerosol-OT (AOT), and a naturally occurring polysaccharide polymer, sodium alginate, were used for synchronized delivery of the two drugs. Balb/c mice bearing syngeneic JC tumors (mammary adenocarcinoma) were used as a drug-resistant tumor model. Nanoparticle-mediated combination therapy significantly inhibited tumor growth and improved animal survival. Nanoparticle-mediated combination treatment resulted in enhanced tumor accumulation of both doxorubicin and methylene blue, significant inhibition of tumor cell proliferation, and increased induction of apoptosis. These data suggest that nanoparticle-mediated combination chemotherapy and photodynamic therapy using doxorubicin and methylene blue has significant therapeutic potential against drug-resistant tumors. Copyright 2009 Elsevier B.V. All rights reserved.

Sleep deprivation and spike-wave discharges in epileptic rats

OpenAIRE

Drinkenburg, W.H.I.M.; Coenen, A.M.L.; Vossen, J.M.H.; Luijtelaar, E.L.J.M. van

1995-01-01

The effects of sleep deprivation were studied on the occurrence of spike-wave discharges in the electroencephalogram of rats of the epileptic WAG/Rij strain, a model for absence epilepsy. This was done before, during and after a period of 12 hours of near total sleep deprivation. A substantial increase in the number of spike-wave discharges was found during the first 4 hours of the deprivation period, whereas in the following deprivation hours epileptic activity returned to baseline values. I...

Derangement of lipid profile in antiepileptic drugs treated patients in local population

International Nuclear Information System (INIS)

Zuberi, N.A.; Perveen, T.

2012-01-01

Epilepsy is the third most common neurological disorder. It is not a single entity. The abnormal electrical activity may result in a variety of events, including loss of consciousness, abnormal movements, a typical or odd behavior or distorted perceptions falls seizers. Epilepsy is a chronic disorder and often requiring years of treatment. A large number of drugs are used for the treatment of epilepsy. The choice among the antiepileptic drugs depends on its effectiveness and side effects. Our retrospective study investigated the effect of anti epileptic drugs on lipid profile. Serum lipid profile was measured in 160 patients in which 40 patients were not started any antiepileptic drug .The remaining 120 patients were receiving antiepileptic drugs (AEDs). 40 control subjects were taken from general population for comparison. The height, weight and body mass index (BMI) and lipid profile of antiepileptic drugs treated patients were compared with control and untreated group. The weight and body mass index of antiepileptic drugs treated group was significantly increased when compared to the control group. Total Cholesterol (TC), Triglyceride (TO), High density lipoprotein (HDL-C), low density lipoprotein (LDL-C), ratio TC/HDL-C and ratio LDL-C/HDL-C were investigated for each group of drugs and controls. TC, TO, LDL-C, ratio TC/HDL-C and ratio LDL-C/HDL-C were significantly increased in patients who were on AEDs when compared with control but HDL-C of all drug treated groups showed significantly decreased when compared with control group. There was significant change in lipid profile was seen in AEDs treated group when compared with control group. Ratio TC/HDL-C and ratio LDUHDL-C alteration showed the risk of atherosclerosis and cardiovascular diseases. Anti-epileptic drugs also alter the BMI and so it could potentially facilitate the development of diabetes mellitus. Our results additionally suggest that there is a need for careful monitoring of lipid profile in

Oral Uncaria rhynchophylla (UR) reduces kainic acid-induced epileptic seizures and neuronal death accompanied by attenuating glial cell proliferation and S100B proteins in rats.

Science.gov (United States)

Lin, Yi-Wen; Hsieh, Ching-Liang

2011-05-17

Epilepsy is a common clinical syndrome with recurrent neuronal discharges in cerebral cortex and hippocampus. Here we aim to determine the protective role of Uncaria rhynchophylla (UR), an herbal drug belong to Traditional Chinese Medicine (TCM), on epileptic rats. To address this issue, we tested the effect of UR on kainic acid (KA)-induced epileptic seizures and further investigate the underlying mechanisms. Oral UR successfully decreased neuronal death and discharges in hippocampal CA1 pyramidal neurons. The population spikes (PSs) were decreased from 4.1 ± 0.4 mV to 2.1 ± 0.3 mV in KA-induced epileptic seizures and UR-treated groups, respectively. Oral UR protected animals from neuronal death induced by KA treatment (from 34 ± 4.6 to 191.7 ± 48.6 neurons/field) through attenuating glial cell proliferation and S100B protein expression but not GABAA and TRPV1 receptors. The above results provide detail mechanisms underlying the neuroprotective action of UR on KA-induced epileptic seizure in hippocampal CA1 neurons. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

Role of Nanodiamonds in Drug Delivery and Stem Cell Therapy.

Science.gov (United States)

Ansari, Shakeel Ahmed; Satar, Rukhsana; Jafri, Mohammad Alam; Rasool, Mahmood; Ahmad, Waseem; Kashif Zaidi, Syed

2016-09-01

The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Nanodiamonds (NDs) have contributed significantly in the development of highly efficient and successful drug delivery systems, and in stem cell therapy. Drug delivery through NDs is an intricate and complex process that deserves special attention to unravel underlying molecular mechanisms in order to overcome certain bottlenecks associated with it. It has already been established that NDs based drug delivery systems have excellent biocompatibility, nontoxicity, photostability and facile surface functionalization properties. There is mounting evidence that suggests that such conjugated delivery systems well retain the properties of nanoparticles like small size, large surface area to volume ratio that provide greater biocatalytic activity to the attached drug in terms of selectivity, loading and stability. NDs based drug delivery systems may form the basis for the development of effective novel drug delivery vehicles with salient features that may facilitate their utility in fluorescence imaging, target specificity and sustainedrelease.

Trigeminal neuralgia: successful antiepileptic drug combination therapy in three refractory cases

Directory of Open Access Journals (Sweden)

Prisco L

2011-08-01

Full Text Available Lara Prisco1, Mario Ganau2, Federica Bigotto1, Francesca Zornada11Department of Anaesthesiology, Intensive Care and Emergency Medicine, University Hospital of Cattinara, 2Graduate School of Nanotechnology, University of Trieste, ItalyAbstract: Antiepileptic drug combination therapy remains an empirical second-line treatment approach in trigeminal neuralgia, after treatment with one antiepileptic drug or other nonantiepileptic drugs have failed. The results in three patients followed in our clinic are not sufficient to draw definitive conclusions, but suggest the possibility of developing this type of therapeutic approach further.Keywords: trigeminal neuralgia, antiepileptic drugs, combination therapy

Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1

DEFF Research Database (Denmark)

Carvill, Gemma L; Heavin, Sinéad B; Yendle, Simone C

2013-01-01

Epileptic encephalopathies are a devastating group of epilepsies with poor prognosis, of which the majority are of unknown etiology. We perform targeted massively parallel resequencing of 19 known and 46 candidate genes for epileptic encephalopathy in 500 affected individuals (cases) to identify...... CHD2 and SYNGAP1 mutations are new causes of epileptic encephalopathies, accounting for 1.2% and 1% of cases, respectively. We also expand the phenotypic spectra explained by SCN1A, SCN2A and SCN8A mutations. To our knowledge, this is the largest cohort of cases with epileptic encephalopathies...

Psychomotor developmental effects of prenatal exposure to psychotropic drugs: a study in EFEMERIS database.

Science.gov (United States)

Hurault-Delarue, Caroline; Damase-Michel, Christine; Finotto, Laurent; Guitard, Claudine; Vayssière, Christophe; Montastruc, Jean-Louis; Montastruc, François; Lacroix, Isabelle

2016-10-01

Little is known about neurodevelopment of children exposed to psychotropic drugs during pregnancy. The purpose of this study was to evaluate the effects of prenatal exposure to psychotropic drugs on psychomotor development in children. This observational study used the EFEMERIS database. The database records the drugs prescribed and delivered during pregnancy and the resulting outcomes. Neurodevelopment at nine and 24 months of children born to women exposed to psychotropic drugs (anxiolytics, antidepressants, neuroleptics and anti-epileptics) during the second and/or third trimesters of pregnancy was compared to children who were not exposed to these drugs. Psychomotor development of 493 children (1.5%) exposed to psychotropic drugs during pregnancy was compared to 32 303 unexposed children. Exposure to psychotropic drugs during pregnancy was associated with an increased risk of abnormal motor development at 9 months (OR = 1.3 [1.1-2.2]) and abnormal motor and mental development at 24 months (OR = 4.8 [2.1-11.0] and OR = 2.3 [1.05-4.9]). Increased risk was observed in children born to women exposed to anti-epileptic drugs, neuroleptics or antidepressants during pregnancy. This study found a higher rate of deviation from the normal developmental milestones in children born to women exposed to psychotropic drugs during pregnancy and more particularly antidepressants, neuroleptics and anti-epileptics. © 2016 Société Française de Pharmacologie et de Thérapeutique.

Optimal Control of Drug Therapy in a Hepatitis B Model

Directory of Open Access Journals (Sweden)

Jonathan E. Forde

2016-08-01

Full Text Available Combination antiviral drug therapy improves the survival rates of patients chronically infected with hepatitis B virus by controlling viral replication and enhancing immune responses. Some of these drugs have side effects that make them unsuitable for long-term administration. To address the trade-off between the positive and negative effects of the combination therapy, we investigated an optimal control problem for a delay differential equation model of immune responses to hepatitis virus B infection. Our optimal control problem investigates the interplay between virological and immunomodulatory effects of therapy, the control of viremia and the administration of the minimal dosage over a short period of time. Our numerical results show that the high drug levels that induce immune modulation rather than suppression of virological factors are essential for the clearance of hepatitis B virus.

Brand-name drug, generic drug, orphan drug. Pharmacological therapy with biosimilar drugs – provision of due diligence in the treatment process

Science.gov (United States)

Zajdel, Justyna

2013-01-01

Due diligence in the process of provision of healthcare services refers, among other elements, to the application of pharmacological therapy at a time which offers the greatest chance for a successful outcome of treatment, i.e. for achieving the optimum expected effect understood as an improvement in the patient's health, reduction of health risks or elimination of the disease. However, due diligence may also refer to actions aimed at ensuring that neither the patient nor the healthcare payer is required to incur unreasonable costs in the process of treatment. The validity of that statement stems not only from normative acts but also from ethical standards laid down in the Medical Code of Ethics (Article 57 section 2). It often happens that the provision of optimal treatment calls for deviations from the formal provisions included in Summary Product Characteristics (SPCs), and the application of drugs that are bioequivalent to reference drugs, which translates into a significant reduction of costs. The present study addresses the problem of acceptability of a specific form of drug substitution consisting in the replacement of a reference drug with a generic drug. Also explored are legal aspects associated with the possibility of therapy based on “off-label use”. The study reviews normative acts existing in the Polish and EU legislation. It also provides a clear definition of orphan drug, which has made it possible to make a distinction and investigate mutual relations between the concepts of brand-name (reference) drug, orphan drug and generic drug. PMID:24592133

Drug therapy for chronic idiopathic axonal polyneuropathy

NARCIS (Netherlands)

Vrancken, A. F. J. E.; van Schaik, I. N.; Hughes, R. A. C.; Notermans, N. C.

2004-01-01

BACKGROUND: Chronic idiopathic axonal polyneuropathy is an insidiously progressive sensory or sensorimotor polyneuropathy that affects elderly people. Although severe disability or handicap does not occur, it reduces quality of life. OBJECTIVES: To assess whether drug therapy for chronic idiopathic

[Drug susceptibility test guided therapy and novel empirical quadruple therapy for Helicobacter pylori infection: a network Meta-analysis].

Science.gov (United States)

Gou, Q Y; Yu, R B; Shi, R H

2017-05-10

Objective: To compare the efficacy and the risk of adverse effect of drug susceptibility test guided therapy and novel empirical quadruple therapy for Helicobacter ( H .) pylori infection. Methods: Literature retrieval was conducted by using major databases. Related papers published up to June 2015 were considered eligible if they were randomized control trials comparing different pharmacological formulations for H. pylori infection and used in a network Meta-analysis and a single rate Meta-analysis to evaluate the relative and absolute rates of H. pylori eradication and the risk of adverse effect. The Jadad score was used to evaluate the methodological quality. Funnel plot was constructed to evaluate the risk of publication bias. Begg's rank correlation test or Egger's regression intercept test was done for the asymmetry of funnel plot. Results: Twenty randomized control trials for the treatment of 6 753 initial treated patients with H. pylori infection were included. Drug susceptibility test guided therapy was significantly superior to concomitant therapy, hybrid therapy, sequential therapy and bismuth quadruple therapy. The culture-based therapy had the highest likelihood of improving clinical efficacy, with lowest risk of adverse effect. Concomitant therapy had the highest probability of causing adverse effect despite its effectiveness. Hybrid therapy and bismuth quadruple therapy were associated with lower risk of adverse effect and higher effectiveness. Conclusion: Drug susceptibility test guided therapy showed superiority to other 4 interventions for H. pylori eradication mentioned above. Hybrid therapy and bismuth quadruple therapy might be applied in the settings where the culture-based strategy is not available.

Drug therapy for people with mental disorders in the view of nursing professionals

Directory of Open Access Journals (Sweden)

Camila Bonfim de Alcântara

2018-03-01

Full Text Available Abstract Objective: To identify the perception of nursing professionals about drug therapy for people with mental disorders. Methods: An exploratory qualitative research was carried out in four Psychosocial Care Centers of Curitiba, Paraná, Brazil. Data, collected from January to March 2015 using an individual semi-structured interview applied to 56 nursing professionals, were submitted to qualitative data analysis and interpretation as proposed by Creswell. Results: The data were organized into three thematic categories: drug therapy improves the life of the person with a mental disorder; negative and positive consequences related to drug therapy; and drug therapy as one of the resources needed to treat mental health. Conclusion: Nursing staff perceive the importance of medications as a resource to treat people with mental disorders as psychotropic drugs minimize he acute symptoms of disorders and improve living conditions when associated with other therapeutic resources.

Agmatine for combined treatment of epilepsy, depression and cognitive impairment in chronic epileptic animals.

Science.gov (United States)

Singh, Tanveer; Bagga, Neetu; Kaur, Anureet; Kaur, Navjot; Gawande, Dinesh Yugraj; Goel, Rajesh Kumar

2017-08-01

Epilepsy is fourth most common neurological disorders associated with depression and cognitive deficits. As per present scenario, none of the antiseizure drugs have been reported successful to have ameliorative effect on epilepsy associated depression and cognitive deficits. Thus, the study was envisioned to assess an ameliorative potential of agmatine on epilepsy and its efficacy and safety for management of associated depression and cognitive deficits. The animals were made epileptic employing pentylenetetrazole (35mg/kg i.p. every 48±2h) kindling model of epilepsy and subsequently were treated with vehicle, valproic acid (300mg/kg/day i.p.) and agmatine (2.5, 5, and 10mg/kg)/day/i.p. for 15days. Except naïve, all the groups were challenged with same pentylenetetrazole dose as employed during kindling on days 5, 10, and 15 to evaluate seizure severity. Two hours after seizure severity test, tail suspension test and passive shock avoidance paradigm was employed to evaluate depression and cognitive behavior respectively. Results suggested that epileptic animals were significantly associated with depression and cognitive impairment. Chronic valproate treatment significantly reduced seizure severity, but was found unable to mitigate depression and cognitive deficits. However, agmatine treatment dose dependently ameliorated seizure severity as well as associated depression and cognitive deficits. On 15th day, animals were euthanized and pertinent neurochemical estimations were carried out in cortical and hippocampal areas of the mice brain. Thus, study concluded that agmatine ameliorated seizure severity, depression and cognitive impairment in epileptic animals, possibly via restoring glutamate-GABA neurotransmission and serotonin synthesis with decreased nitrosative stress. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Celiac Disease and Drug-Based Therapies: Inquiry into Patients Demands.

Science.gov (United States)

Branchi, Federica; Tomba, Carolina; Ferretti, Francesca; Norsa, Lorenzo; Roncoroni, Leda; Bardella, Maria Teresa; Conte, Dario; Elli, Luca

2016-01-01

Medical research is looking for alternative drug-based options to the gluten-free diet (GFD) for celiac disease. We aimed at evaluating the need for alternative therapies perceived by celiac patients. During the 2013 meeting of the Lombardy section of the Italian Celiac Patients Association, adult subjects were invited to fill in a questionnaire investigating their clinical profile in relation to compliance to the diet, quality of life (QOL) as well as their opinion on alternative therapies. Three hundred and seventy two patients (76 m, mean age 41.7 ± 13.9 years) completed the questionnaire. Patients reported a significant improvement in health status (HS) and QOL after the diet was started (p < 0.001). The GFD was accepted by 88% patients, but the need for alternative therapies was reported by 65%. Subjects expressing the need for a drug-based therapy showed a lower increase in QOL (p = 0.003) and HS (p = 0.005) on GFD. The preferred option for an alternative therapy was the use of enzymes (145 subjects), followed by a vaccine (111 subjects). The GFD is favorably accepted by most celiac patients. Nevertheless, a proportion of patients pronounce themselves in favor of the development of alternative drugs. © 2016 S. Karger AG, Basel.

Drug therapy problems identification by clinical pharmacists in a private hospital in Kuwait.

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Bayoud, T; Waheedi, M; Lemay, J; Awad, A

2018-05-01

To report the types and frequency of drug therapy problems (DTPs) identified and the physician acceptance of the clinical pharmacist interventions in a private hospital in Kuwait. A retrospective cross-sectional study was conducted on 3500 patients admitted to the hospital between December 2010 and April 2013. A structured approach was used to identify DTPs and recommend interventions. Data were analyzed using MAXQDA version 11. A total of 670 DTPs were identified and recommendations were proposed to treating physicians for each DTP. Overdosage was the most frequently identified drug therapy problem (30.8%), followed by low dosage (17.6%), unnecessary drug therapy (17.3%), need for additional drug therapy (11.6%), and need for different drug product (11.6%). The drug classes most frequently involved were anti-infectives (36.9%), analgesics (25.2%), and gastrointestinal agents (15.5%). More than two-third of the interventions (67.5%) were accepted and implemented by physicians. The most frequently accepted interventions were related to nonadherence, adverse drug reaction, monitoring parameters, inappropriate dosage, and need for additional drug therapy. The current findings expand the existing body of data by reporting on pharmacist recommendations of identified DTPs and importantly, their high rate of acceptance and implementation by the treating physician. These results could serve as a springboard to support further development and implementation of clinical pharmacy services in other healthcare settings in Kuwait. Copyright © 2018 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy

DEFF Research Database (Denmark)

Stenvang, Jan; Kümler, Iben; Nygård, Sune Boris

2013-01-01

-standard chemotherapeutic drug will be relatively low in such a patient cohort it is a pre-requisite that such testing is based on predictive biomarkers. This review describes our strategy of biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy, taking the repurposing of topoisomerase I (Top1...

International veterinary epilepsy task force recommendations for systematic sampling and processing of brains from epileptic dogs and cats.

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Matiasek, Kaspar; Pumarola I Batlle, Martí; Rosati, Marco; Fernández-Flores, Francisco; Fischer, Andrea; Wagner, Eva; Berendt, Mette; Bhatti, Sofie F M; De Risio, Luisa; Farquhar, Robyn G; Long, Sam; Muñana, Karen; Patterson, Edward E; Pakozdy, Akos; Penderis, Jacques; Platt, Simon; Podell, Michael; Potschka, Heidrun; Rusbridge, Clare; Stein, Veronika M; Tipold, Andrea; Volk, Holger A

2015-08-28

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete clinical work-up. This may be due to sparse training in epilepsy pathology and or due to lack of neuropathological guidelines for companion animals.The protocols introduced herein shall facilitate systematic sampling and processing of epileptic brains and therefore increase the efficacy, reliability and reproducibility of morphological studies in animals suffering from seizures.Brain dissection protocols of two neuropathological centres with research focus in epilepsy have been optimised with regards to their diagnostic yield and accuracy, their practicability and their feasibility concerning clinical research requirements.The recommended guidelines allow for easy, standardised and ubiquitous collection of brain regions, relevant for seizure generation. Tissues harvested the prescribed way will increase the diagnostic efficacy and provide reliable material for scientific investigations.

Modeling epileptic brain states using EEG spectral analysis and topographic mapping.

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Direito, Bruno; Teixeira, César; Ribeiro, Bernardete; Castelo-Branco, Miguel; Sales, Francisco; Dourado, António

2012-09-30

Changes in the spatio-temporal behavior of the brain electrical activity are believed to be associated to epileptic brain states. We propose a novel methodology to identify the different states of the epileptic brain, based on the topographic mapping of the time varying relative power of delta, theta, alpha, beta and gamma frequency sub-bands, estimated from EEG. Using normalized-cuts segmentation algorithm, points of interest are identified in the topographic mappings and their trajectories over time are used for finding out relations with epileptogenic propagations in the brain. These trajectories are used to train a Hidden Markov Model (HMM), which models the different epileptic brain states and the transition among them. Applied to 10 patients suffering from focal seizures, with a total of 30 seizures over 497.3h of data, the methodology shows good results (an average point-by-point accuracy of 89.31%) for the identification of the four brain states--interictal, preictal, ictal and postictal. The results suggest that the spatio-temporal dynamics captured by the proposed methodology are related to the epileptic brain states and transitions involved in focal seizures. Copyright © 2012 Elsevier B.V. All rights reserved.

Cerebral perfusion alterations in epileptic patients during peri-ictal and post-ictal phase: PASL vs DSC-MRI.

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Pizzini, Francesca B; Farace, Paolo; Manganotti, Paolo; Zoccatelli, Giada; Bongiovanni, Luigi G; Golay, Xavier; Beltramello, Alberto; Osculati, Antonio; Bertini, Giuseppe; Fabene, Paolo F

2013-07-01

Non-invasive pulsed arterial spin labeling (PASL) MRI is a method to study brain perfusion that does not require the administration of a contrast agent, which makes it a valuable diagnostic tool as it reduces cost and side effects. The purpose of the present study was to establish the viability of PASL as an alternative to dynamic susceptibility contrast (DSC-MRI) and other perfusion imaging methods in characterizing changes in perfusion patterns caused by seizures in epileptic patients. We evaluated 19 patients with PASL. Of these, the 9 affected by high-frequency seizures were observed during the peri-ictal period (within 5hours since the last seizure), while the 10 patients affected by low-frequency seizures were observed in the post-ictal period. For comparison, 17/19 patients were also evaluated with DSC-MRI and CBF/CBV. PASL imaging showed focal vascular changes, which allowed the classification of patients in three categories: 8 patients characterized by increased perfusion, 4 patients with normal perfusion and 7 patients with decreased perfusion. PASL perfusion imaging findings were comparable to those obtained by DSC-MRI. Since PASL is a) sensitive to vascular alterations induced by epileptic seizures, b) comparable to DSC-MRI for detecting perfusion asymmetries, c) potentially capable of detecting time-related perfusion changes, it can be recommended for repeated evaluations, to identify the epileptic focus, and in follow-up and/or therapy-response assessment. Copyright © 2013 Elsevier Inc. All rights reserved.

Possible roles for frequent salivary antiepileptic drug monitoring in the management of epilepsy.

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Herkes, G K; Eadie, M J

1990-07-01

Salivary levels of phenytoin, phenobarbitone, carbamazepine and carbamazepine-epoxide correlate with the simultaneous plasma water levels of these substances, after correcting for the effects of pH differences between saliva and plasma in the case of phenobarbitone. Saliva is easy and painless to collect, and salivary levels of the drugs are conveniently measured. Frequent (often daily) monitoring of pre-dose morning anticonvulsant drug concentrations in saliva over periods of weeks or months in 3 groups of epileptic subjects showed that (i) in some but not all poorly controlled epileptic patients seizures tended to occur on days when salivary anticonvulsant levels were lower than on non-seizure days, (ii) in such subjects it was possible to estimate an anticipated optimal drug concentration and dose to minimize seizure activity from the plot of seizure frequency against drug concentrations, (iii) in women with 'catamenial' epilepsy, salivary anticonvulsant levels were lower on perimenstrual days than at mid-cycle in half of the subjects studied, and (iv) in pregnant epileptic women the time course of the change in drug levels relative to dose could be followed more closely throughout pregnancy and the post-natal period than was practicable when using blood level measurements. Frequent measurement of salivary anticonvulsant concentrations appears a promising and inexpensive adjunct to the investigation and management of certain problem areas in epilepsy.

Drug therapy for peripheral vestibular vertigo

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L. M. Antonenko

2017-01-01

Full Text Available The choice of effective treatments for vestibular vertigo is one of the important problems, by taking into account the high prevalence of peripheral vestibular diseases. Different drugs, such as vestibular suppressants for the relief of acute vertigo attacks and vestibular compensation stimulants for rehabilitation treatment, are used to treat vestibular vertigo. Drug therapy in combination with vestibular exercises is effective in patients with vestibular neuronitis, Meniere's disease, so is that with therapeutic maneuvers in patients with benign paroxysmal positional vertigo. The high therapeutic efficacy and safety of betahistines permit their extensive use for the treatment of various vestibular disorders.

Nanomaterial-based drug delivery carriers for cancer therapy

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Feng, Tao

2017-01-01

This brief summarizes different types of organic and inorganic nanomaterials for drug delivery in cancer therapy. It highlights that precisely designed nanomaterials will be the next-generation therapeutic agents for cancer treatment.

De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies

DEFF Research Database (Denmark)

2014-01-01

in five individuals and de novo mutations in GABBR2, FASN, and RYR3 in two individuals each. Unlike previous studies, this cohort is sufficiently large to show a significant excess of de novo mutations in epileptic encephalopathy probands compared to the general population using a likelihood analysis (p...... = 8.2 × 10(-4)), supporting a prominent role for de novo mutations in epileptic encephalopathies. We bring statistical evidence that mutations in DNM1 cause epileptic encephalopathy, find suggestive evidence for a role of three additional genes, and show that at least 12% of analyzed individuals have...... analyzed exome-sequencing data of 356 trios with the "classical" epileptic encephalopathies, infantile spasms and Lennox Gastaut syndrome, including 264 trios previously analyzed by the Epi4K/EPGP consortium. In this expanded cohort, we find 429 de novo mutations, including de novo mutations in DNM1...

Epileptic Seizures Versus Syncope: Pathophysiology and Clinical Approach

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Marios Charalambous

2017-02-01

Full Text Available Generalised epileptic seizures and syncope are two syndromes with similar clinical manifestation and their differentiation can be quite challenging. The aim of this review is to use an evidence-based approach in differentiating these two syndromes through the comprehension of the pathophysiological mechanisms involved and their clinical signs. Both syndromes affect regions of the forebrain and consciousness level, although, different mechanisms are involved. Syncope is a paroxysmal event secondary to a short-term decrease in cerebral perfusion, oxygenation or essential nutrients delivery. Generalised epileptic seizure activity is defined as the clinical manifestation of transient paroxysmal disturbances in brain function secondary to an imbalance between excitatory and inhibitory neurotransmitters. Clinical criteria, including precipitating events, clinical signs preceding, during and following the episodes and event duration, can be used to differentiate the two syndromes. Although these criteria might be useful for the practitioner, definite conclusions should be precluded due to the lack of original research articles and weak evidence on this specific field.Application: The review might be a useful tool for the general practitioner and clinical scientist as it will aid towards the differentiation of two syndromes, i.e. generalised epileptic seizures and syncope, with similar clinical presentation.

Microsponges based novel drug delivery system for augmented arthritis therapy.

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Osmani, Riyaz Ali M; Aloorkar, Nagesh H; Ingale, Dipti J; Kulkarni, Parthasarathi K; Hani, Umme; Bhosale, Rohit R; Jayachandra Dev, Dandasi

2015-10-01

The motive behind present work was to formulate and evaluate gel containing microsponges of diclofenac diethylamine to provide prolonged release for proficient arthritis therapy. Quasi-emulsion solvent diffusion method was implied using Eudragit RS-100 and microsponges with varied drug-polymer ratios were prepared. For the sake of optimization, diverse factors affecting microparticles physical properties were too investigated. Microsponges were characterized by SEM, DSC, FT-IR, XRPD and particle size analysis, and evaluated for morphology, drug loading, in vitro drug release and ex vivo diffusion as well. There were no chemical interactions between drug and polymers used as revealed by compatibility studies outcomes. The drug polymer ratio reflected notable effect on drug content, encapsulation efficiency and particle size. SEM results revealed spherical microsponges with porous surface, and had 7.21 μm mean particle size. The microsponges were then incorporated in gel; which exhibited viscous modulus along with pseudoplastic behavior. In vitro drug release results depicted that microsponges with 1:2 drug-polymer ratio were more efficient to give extended drug release of 75.88% at the end of 8 h; while conventional formulation get exhausted incredibly earlier by releasing 81.11% drug at the end of 4 h only. Thus the formulated microsponge-based gel of diclofenac diethylamine would be a promising alternative to conventional therapy for safer and efficient treatment of arthritis and musculoskeletal disorders.

Mental development of tuberous sclerosis with regard to epileptic seizures and CT findings

International Nuclear Information System (INIS)

Katafuchi, Yukihiko; Ishihara, Osamu; Matsuishi, Toyojiro; Shiotsuki, Yuko; Yamaguchi, Yoichiro; Imuta, Fusae

1985-01-01

The relation of mental development to epileptic seizures and CT findings was examined in 17 patients with tuberous sclerosis. Epileptic seizures occurred in 16 of the 17 patients. The earlier it occurred, the higher the incidence of mental retardation was. There was no constant correlation between mental development and the type of epileptic seizures or the attainment of inhibition of seizures. In two patients in whom calcification spreading to the cerebral cortex and subcortical region was detected on CT, in addition to calcified tubercles around the cerebral ventricle, an intelligence quotient was significantly lower than in the other patients. (Namekawa, K.)

The application of machine learning techniques in the clinical drug therapy.

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Meng, Huan-Yu; Jin, Wan-Lin; Yan, Cheng-Kai; Yang, Huan

2018-05-25

The development of a novel drug is an extremely complicated process that includes the target identification, design and manufacture, and proper therapy of the novel drug, as well as drug dose selection, drug efficacy evaluation, and adverse drug reaction control. Due to the limited resources, high costs, long duration, and low hit-to-lead ratio in the development of pharmacogenetics and computer technology, machine learning techniques have assisted novel drug development and have gradually received more attention by researchers. According to current research, machine learning techniques are widely applied in the process of the discovery of new drugs and novel drug targets, the decision surrounding proper therapy and drug dose, and the prediction of drug efficacy and adverse drug reactions. In this article, we discussed the history, workflow, and advantages and disadvantages of machine learning techniques in the processes mentioned above. Although the advantages of machine learning techniques are fairly obvious, the application of machine learning techniques is currently limited. With further research, the application of machine techniques in drug development could be much more widespread and could potentially be one of the major methods used in drug development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Mortality predictors of epilepsy and epileptic seizures among hospitalized elderly

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Telma M. R Assis

2015-06-01

Full Text Available Epilepsy and epileptic seizures are common brain disorders in the elderly and are associated with increased mortality that may be ascribed to the underlying disease or epilepsy-related causes.Objective To describe mortality predictors of epilepsy and epileptic seizures in elderly inpatients.Method Retrospective analysis was performed on hospitalized elderly who had epilepsy or epileptic seizures, from January 2009 to December 2010. One hundred and twenty patients were enrolled.Results The most common etiology was ischemic stroke (37%, followed by neoplasias (13%, hemorrhagic stroke (12%, dementias (11.4% and metabolic disturbances (5.5%. In a univariate analysis, disease duration (p = 0.04, status epilepticus (p < 0.001 and metabolic etiology (p = 0.005 were associated with mortality. However after adjustment by logistic regression, only status epilepticus remained an independent predictor of death (odds ratio = 13; 95%CI = 2.3 to 72; p = 0.004.Conclusion In this study status epilepticus was an independent risk factor for death during hospitalization.

The influence of folate serum levels on depressive mood and mental processing in patients with epilepsy treated with enzyme-inducing anti-epileptic drugs.

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Rösche, J; Uhlmann, C; Weber, R; Fröscher, W

2003-04-01

Folate deficiency is common in patients with epilepsy and also occurs in patients with depression or cognitive deficits. This study investigates whether low serum folate levels may contribute to depressive mood and difficulties in mental processing in patients with epilepsy treated with anti-epileptic drugs inducing the cytochrome P450. We analysed the serum folate levels, the score in the Self Rating Depression Scale (SDS) and the results of a bedside test in mental processing in 54 patients with epilepsy. There was a significant negative correlation between the serum folate levels and the score in SDS and significant positive correlations between the score in SDS and the time needed to process an interference task or a letter-reading task. Low serum folate levels may contribute to depressive mood and therefore to difficulties in mental processing. Further studies utilizing total plasma homocysteine as a sensitive measure of functional folate deficiency and more elaborate tests of mental processing are required to elucidate the impact of folate metabolism on depressive mood and cognitive function in patients with epilepsy.

Epileptic seizures, coma and EEG burst-suppression from suicidal bupropion intoxication.

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Noda, Anna Hiro; Schu, Ulrich; Maier, Tanja; Knake, Susanne; Rosenow, Felix

2017-03-01

Bupropion, an amphetamine-like dual mechanism drug, is approved and increasingly used for the treatment of major depression, and its use is associated with a dose-dependent risk of epileptic seizures. Suicide attempts are frequent in major depression and often an overdose of the drugs available is ingested. Therefore, it is important to be aware of the clinical course, including EEG and neurological symptoms, as well as treatment and prognosis of bupropion intoxication. We report on the clinical and EEG course of a women who ingested 27 g of bupropion in a suicide attempt. Myoclonic seizures were followed by generalized tonic-clonic seizures and coma associated with EEG burst-suppression and brief tonic seizures. Active carbon and neuro-intensive care treatment, including respiratory support, were given. Within three days, the patient returned to a stable clinical condition with a mildly encephalopathic EEG. In conclusion, bupropion intoxication requires acute intensive care treatment and usually has a good prognosis, however, misinterpretation of the clinical and EEG presentation may lead to errors in management.

Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance in vitro.

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Khdair, Ayman; Handa, Hitesh; Mao, Guangzhao; Panyam, Jayanth

2009-02-01

Drug resistance limits the success of many anticancer drugs. Reduced accumulation of the drug at its intracellular site of action because of overexpression of efflux transporters such as P-glycoprotein (P-gp) is a major mechanism of drug resistance. In this study, we investigated whether photodynamic therapy (PDT) using methylene blue, also a P-gp inhibitor, can be used to enhance doxorubicin-induced cytotoxicity in drug-resistant tumor cells. Aerosol OT (AOT)-alginate nanoparticles were used as a carrier for the simultaneous cellular delivery of doxorubicin and methylene blue. Methylene blue was photoactivated using light of 665 nm wavelength. Induction of apoptosis and necrosis following treatment with combination chemotherapy and PDT was investigated in drug-resistant NCI/ADR-RES cells using flow cytometry and fluorescence microscopy. Effect of encapsulation in nanoparticles on the intracellular accumulation of doxorubicin and methylene blue was investigated qualitatively using fluorescence microscopy and was quantitated using HPLC. Encapsulation in AOT-alginate nanoparticles significantly enhanced the cytotoxicity of combination therapy in resistant tumor cells. Nanoparticle-mediated combination therapy resulted in a significant induction of both apoptosis and necrosis. Improvement in cytotoxicity could be correlated with enhanced intracellular and nuclear delivery of the two drugs. Further, nanoparticle-mediated combination therapy resulted in significantly elevated reactive oxygen species (ROS) production compared to single drug treatment. In conclusion, nanoparticle-mediated combination chemotherapy and PDT using doxorubicin and methylene blue was able to overcome resistance mechanisms and resulted in improved cytotoxicity in drug-resistant tumor cells.

Drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy.

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Gheorghe, Liana; Cotruta, Bogdan; Trifu, Viorel; Cotruta, Cristina; Becheanu, Gabriel; Gheorghe, Cristian

2008-09-01

Pegylated interferon-alpha in combination with ribavirin currently represents the therapeutic standard for the hepatitis C virus infection. Interferon based therapy may be responsible for many cutaneous side effects. We report a case of drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy. To our knowledge, this is the first reported case of Sweet's syndrome in association with pegylated interferon-alpha therapy.

The comprehension of drug therapy in elderly in a family health unit

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Maria Carolina Martinghi Spinola Moretti

2018-04-01

Full Text Available Introduction: The complex therapeutic regimen and aging changes contribute to the difficulty of understanding the drug therapy and treatment adherence. Objective: To evaluate the comprehension of drug therapy for elderly identifying the limiting factors to its adherence to the treatment. Methods: A descriptive, exploratory and quantitative study using na evaluation questionnaire of the comprehension of the drug therapy, mini-mental state examination and the Lawton scale in patients from the Adult Program of a Family Health Unit, in nearby São Paulo, SP, Brazil. Data were analyzed by χ2 tests or Fisher’s exact test, of Mann-Whitney or Kruskal-Wallis. Results: The sample consisted of 50 elderly patients with diabetes and/or arterial hypertension with the average age of 68.8 years and low education. Only 30% of them knew the name of the medications that they make use of, 6% understood the letter of the prescription, 24% thought there is no need to take their medications when they feel good; and 20% have abandoned treatment sometime. The factors that influenced the comprehension of the drug therapy were marital status, family composition, cognitive status, number of pills/day and level of education. Conclusion: The lack of understanding by the elderly about their drug therapy may hinder to its adherence to the treatment, lead to poor control of symptoms, and interfere directly in their health and quality of life.

Prolonged exposure therapy for the treatment of patients diagnosed with psychogenic non-epileptic seizures (PNES) and post-traumatic stress disorder (PTSD).

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Myers, Lorna; Vaidya-Mathur, Urmi; Lancman, Marcelo

2017-01-01

Although there is general consensus that psychogenic non-epileptic seizures (PNES) are treated with psychotherapy, the effectiveness of most psychotherapeutic modalities remains understudied. In this treatment series of 16 patients dually diagnosed with PNES and post-traumatic stress disorder (PTSD), we evaluated the effect of prolonged exposure therapy (PE) on reduction of PNES. Secondary measures included Beck Depression Inventory (BDI-II) and Post-Traumatic Disorder Diagnostic Scale (PDS). Subjects diagnosed with video EEG-confirmed PNES and PTSD confirmed through neuropsychological testing and clinical interview were treated with traditional PE psychotherapy with certain modifications for the PNES. Treatment was conducted over the course of 12-15 weekly sessions. Seizure frequency was noted in each session by examining the patients' seizure logs, and mood and PTSD symptomatology was assessed at baseline and on the final session. Eighteen subjects enrolled, and 16 (88.8%) completed the course of treatment. Thirteen of the 16 (81.25%) therapy completers reported no seizures by their final PE session, and the other three reported a decline in seizure frequency (Z=-3.233, p=0.001). Mean scores on scales of depression (M=-13.56, SD=12.27; t (15)=-4.420, pPTSD symptoms (M=-17.1875, SD=13.01; t (15)=-5.281, pPTSD reduced the number of PNES and improved mood and post traumatic symptomatology. Follow-up revealed that gains made in seizure control on the last day of treatment were maintained over time. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Recent advances in targeted drug therapy for hepatocellular carcinoma

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FAN Yongqiang

2018-02-01

Full Text Available More and more clinical trials have proved the efficacy of targeted drugs in the treatment of hepatocellular carcinoma (HCC. With the development of science and technology, more and more targeted drugs have appeared. In recent years, targeted drugs such as regorafenib and ramucirumab have shown great potential in related clinical trials. In addition, there are ongoing clinical trials for second-line candidate drugs, such as c-Met inhibitors tivantinib and cabozantinib and a VEGFR-2 inhibitor ramucirumab. This article summarizes the advances in targeted drug therapy for HCC and related trial data, which provides a reference for further clinical trials and treatment.

Laboratory findings in neurosyphilis patients with epileptic seizures alone as the initial presenting symptom.

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Tong, Man-Li; Liu, Li-Li; Zeng, Yan-Li; Zhang, Hui-Lin; Liu, Gui-Li; Zheng, Wei-Hong; Dong, Jie; Wu, Jing-Yi; Su, Yuan-Hui; Lin, Li-Rong; Yang, Tian-Ci

2013-04-01

A retrospective chart review was performed to characterize the clinical presentation, the characteristic combination of serologic and cerebrospinal fluid (CSF) abnormalities, and the neuroimaging findings of neurosyphilis (NS) patients who had epileptic seizures alone as an initial presenting symptom. In a 6.75-year period, 169 inpatients with NS were identified at Zhongshan Hospital (from June 2005 to February 2012). We demonstrated that 13 (7.7%) of the 169 NS patients had epileptic seizures alone as an initial presenting feature. Epileptic seizures occurred in NS patients with syphilitic meningitis (2 cases), meningovascular NS (5 cases), and general paresis (6 cases). The types of epileptic seizures included simple partial, complex partial with secondary generalization (including status epilepticus), and generalized seizures (no focal onset reported). Nine of NS patients with only epileptic seizures as primary symptom were misdiagnosed, and the original misdiagnosis was 69.23% (9/13). Ten (10/13, 76.9%) patients had an abnormal magnetic resonance imaging, and 7 (7/13 53.8%) patients had abnormal electroencephalogram recordings. In addition, the sera rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TPPA) from all 13 patients were positive. The overall positive rates of the CSF-RPR and CSF-TPPA were 61.5% and 69.2%, respectively. Three patients demonstrated CSF pleocytosis, and 9 patients exhibited elevated CSF protein levels. Therefore, NS with only epileptic seizures at the initial presentation exhibits a lack of specificity. It is recommended that every patient with clinically evident symptoms of epileptic seizures should have a blood test performed for syphilis. When the serology results are positive, all of the patients should undergo a CSF examination to diagnose NS. Copyright © 2013 Elsevier Inc. All rights reserved.

Clinical Microbiological Aspects of Epileptic Seizures in the Tropical Countries with Specific Focus on Nigeria

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Ijeoma Kanu

2005-01-01

Full Text Available Epilepsy is a common neurological disorder; however, in Nigeria and other tropical regions, the causes of epileptic seizures differ greatly in etiology. This paper is an attempt to highlight some possible microbiological aspects of epileptic seizures. A literature review was carried out to identify the extent to which microbial infections were involved in the elicitation of epileptic seizures. Data were collected from several clinics in the community and hospitals in Nigeria and correlated with the evidence from the literature review. It was found that different microbial agents including viral, bacterial, protozoa, and fungal agents were involved in several aspects of epileptic seizures. Malaria was found to cause more than 88% of childhood epileptic seizures and 12% of adult seizures. Generalized tonic-clonic seizures occurred in more than 40% of adult patients. Partial seizures were uncommon. Cases of epileptic seizures associated with bacteria (e.g., brucellosis, viral, fungal, and protozoa infections were frequently reported. Malaria, tapeworm, and cysticercosis were some of the common infectious causes of epilepsy; however, in some cases, the cause remained unknown. From these findings, it was evident that microbiological aspects of epilepsies are possible research areas that might be developed. It is believed that the unraveling of the various microbiological factors in epileptic seizures would have important implications for understanding the underlying neurobiology, evaluating treatment strategies, and perhaps planning health-care resources for the affected. It will also help to improve the prognostic factors in initial seizure symptomatic etiology and presence of any structural cerebral abnormalities.

Modeling antibiotic treatment in hospitals: A systematic approach shows benefits of combination therapy over cycling, mixing, and mono-drug therapies.

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Tepekule, Burcu; Uecker, Hildegard; Derungs, Isabel; Frenoy, Antoine; Bonhoeffer, Sebastian

2017-09-01

Multiple treatment strategies are available for empiric antibiotic therapy in hospitals, but neither clinical studies nor theoretical investigations have yielded a clear picture when which strategy is optimal and why. Extending earlier work of others and us, we present a mathematical model capturing treatment strategies using two drugs, i.e the multi-drug therapies referred to as cycling, mixing, and combination therapy, as well as monotherapy with either drug. We randomly sample a large parameter space to determine the conditions determining success or failure of these strategies. We find that combination therapy tends to outperform the other treatment strategies. By using linear discriminant analysis and particle swarm optimization, we find that the most important parameters determining success or failure of combination therapy relative to the other treatment strategies are the de novo rate of emergence of double resistance in patients infected with sensitive bacteria and the fitness costs associated with double resistance. The rate at which double resistance is imported into the hospital via patients admitted from the outside community has little influence, as all treatment strategies are affected equally. The parameter sets for which combination therapy fails tend to fall into areas with low biological plausibility as they are characterised by very high rates of de novo emergence of resistance to both drugs compared to a single drug, and the cost of double resistance is considerably smaller than the sum of the costs of single resistance.

Recurrent occurrences of CDKL5 mutations in patients with epileptic encephalopathy.

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Yamamoto, Toshiyuki; Shimojima, Keiko; Kimura, Nobusuke; Mogami, Yukiko; Usui, Daisuke; Takayama, Rumiko; Ikeda, Hiroko; Imai, Katsumi

2015-01-01

The cyclin-dependent kinase-like 5 gene (CDKL5) is recognized as one of the genes responsible for epileptic encephalopathy. We identified CDKL5 mutations in five Japanese patients (one male and four female) with epileptic encephalopathy. Although all mutations were of de novo origin, they were located in the same positions as previously reported pathogenic mutations. These recurrent occurrences of de novo mutations in the same loci may indicate hot spots of nucleotide alteration.

Thirty Years of Orphan Drug Legislation and the Development of Drugs to Treat Rare Seizure Conditions: A Cross Sectional Analysis.

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Döring, Jan Henje; Lampert, Anette; Hoffmann, Georg F; Ries, Markus

2016-01-01

Epilepsy is a serious chronic health condition with a high morbidity impairing the life of patients and afflicted families. Many epileptic conditions, especially those affecting children, are rare disorders generating an urgent medical need for more efficacious therapy options. Therefore, we assessed the output of the US and European orphan drug legislations. Quantitative analysis of the FDA and EMA databases for orphan drug designations according to STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) criteria. Within the US Orphan Drug Act 40 designations were granted delivering nine approvals, i.e. clobazam, diazepam viscous solution for rectal administration, felbamate, fosphenytoin, lamotrigine, repository corticotropin, rufinamide, topiramate, and vigabatrin. Since 2000 the EMA granted six orphan drug designations whereof two compounds were approved, i.e. rufinamide and stiripentol. In the US, two orphan drug designations were withdrawn. Orphan drugs were approved for conditions including Lennox-Gastaut syndrome, infantile spasms, Dravet syndrome, and status epilepticus. Comparing time to approval for rufinamide, which was approved in the US and the EU to treat rare seizure conditions, the process seems faster in the EU (2.2 years) than in the US (4.3 years). Orphan drug development in the US and in the EU delivered only few molecular entities to treat rare seizure disorders. The development programs focused on already approved antiepileptic drugs or alternative pharmaceutical formulations. Most orphan drugs approved in the US are not approved in the EU to treat rare seizures although some were introduced after 2000 when the EU adopted the Orphan Drug Regulation.

Medical emergencies facing general practitioners: Drugs for the doctor's bag

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Janković Slobodan

2014-01-01

Full Text Available General practitioners are frequently facing medical emergencies. In order to react properly and administer therapy on time, a general practitioner needs to prepare and keep with himself the appropriate set of drugs which could be effectively used for treatment of the emergencies. The following drugs should find their place in the doctor's bag: acetaminophen (for mild and moderate pain, and for fever, morphine (for severe pain, naloxone (for heroin poisoning, ceftriaxone (for meningococcal meningitis, albuterol (for bronchial asthma attack, hydrocortisone (for bronchial asthma attack, glucagon (for severe hypoglycemia, dextrose (for mild to moderate hypoglycemia, diazepam (for febrile convulsions or epileptic status, epinephrine (for anaphylaxis and cardiac arrest, atropine (for symptomatic bradicardia, chloropyramine (for acute allergy, aspirin (for acute myocardial infarction, nitroglycerine (for acute coronary syndrome, metoclopramide (for nausea and vomiting, haloperidol (for delirium, methylergometrine (for control of bleeding after delivery or abortion, furosemide (for acute pulmonary edema and flumazenil (for benzodiazepine poisoning. For each of the listed drugs a physician should well know the recommended doses, indications, contraindications and warnings. All of the listed drugs are either registered in Serbia or available through special import, so general practitioners may fill their bags with all necessary drugs and effectively and safely treat medical emergencies.

Ketogenic Diet in Epileptic Encephalopathies

OpenAIRE

Sharma, Suvasini; Tripathi, Manjari

2013-01-01

The ketogenic diet is a medically supervised high-fat, low-carbohydrate diet that has been found useful in patients with refractory epilepsy. It has been shown to be effective in treating multiple seizure types and epilepsy syndromes. In this paper, we review the use of the ketogenic diet in epileptic encephalopathies such as Ohtahara syndrome, West syndrome, Dravet syndrome, epilepsy with myoclonic atonic seizures, and Lennox-Gastaut syndrome.

Non-Steroidal Anti-inflammatory Drugs As Host-Directed Therapy for Tuberculosis : A Systematic Review

NARCIS (Netherlands)

Kroesen, Vera M.; Gröschel, Matthias I.; Martinson, Neil; Zumla, Alimuddin; Maeurer, Markus; van der Werf, Tjip S.; Vilaplana, Cristina

2017-01-01

Lengthy, antimicrobial therapy targeting the pathogen is the mainstay of conventional tuberculosis treatment, complicated by emerging drug resistances. Host-directed therapies, including non-steroidal anti-inflammatory drugs (NSAIDs), in contrast, target host factors to mitigate disease severity. In

Anticonvulsant therapy in brain-tumor related epilepsy

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Fröscher Walter

2016-06-01

Full Text Available Background. The lifetime risk of patients with brain tumors to have focal epileptic seizures is 10-100%; the risk depends on different histology. Specific guidelines for drug treatment of brain tumor-related seizures have not yet been established.

Medical management of epileptic seizures: challenges and solutions

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Sarma AK

2016-02-01

Full Text Available Anand K Sarma,1 Nabil Khandker,1 Lisa Kurczewski,2 Gretchen M Brophy2 1Department of Neurology, 2Departments of Pharmacotherapy & Outcomes Science and Neurosurgery, Virginia Commonwealth University, Richmond, VA, USA Abstract: Epilepsy is one of the most common neurologic illnesses. This condition afflicts 2.9 million adults and children in the US, leading to an economic impact amounting to $15.5 billion. Despite the significant burden epilepsy places on the population, it is not very well understood. As this understanding continues to evolve, it is important for clinicians to stay up to date with the latest advances to provide the best care for patients. In the last 20 years, the US Food and Drug Administration has approved 15 new antiepileptic drugs (AEDs, with many more currently in development. Other advances have been achieved in terms of diagnostic modalities like electroencephalography technology, treatment devices like vagal nerve and deep-brain stimulators, novel alternate routes of drug administration, and improvement in surgical techniques. Specific patient populations, such as the pregnant, elderly, those with HIV/AIDS, and those with psychiatric illness, present their own unique challenges, with AED side effects, drug interactions, and medical–psychiatric comorbidities adding to the conundrum. The purpose of this article is to review the latest literature guiding the management of acute epileptic seizures, focusing on the current challenges across different practice settings, and it discusses studies in various patient populations, including the pregnant, geriatric, those with HIV/AIDS, comatose, psychiatric, and “pseudoseizure” patients, and offers possible evidence-based solutions or the expert opinion of the authors. Also included is information on newer AEDs, routes of administration, and significant AED-related drug-interaction tables. This review has tried to address only some of these issues that any practitioner who

Epileptic seizures due to multiple cerebral cavernomatosis

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Spasić Mirjana

2007-01-01

Full Text Available Background. Cavernous angiomas are angiographically occult vascular malformations that are present in 0.4−0.9 % of people, and represent around 5% of all cerebrovascular malformations. They can be single or multiple, and sporadic or familial. The presence of multiple lesions is more frequent in familial cavernomatosis. Ten to 30 % are associated with familial clustering. Case report. We presented the case of a 43-year-old man, admitted to the Emergency Department due to unprovoked seizure during the wide awake and everyday activities. Neurological examination was with no focal signs. A 32-channel standard digital EEG was without any significant changes of normal baseline activity. After sleep deprivation EEG showed multifocal, bilateral and asymmetric polyspikes and sharpwaves activity. Hyperventilation induced generalized epileptiform discharges. MRI scan demonstrated multiple small cavernous angiomas. Neuropsychological testing demonstrated a delayed memory impairment. Neurosurgery treatment was not recommended, and the therapy with valproate 1 250 mg/day had an excellent efficacy with no singnificant adverse effects. Conclusion. This patient considered as a rare case with multiple cavernomatosis highlights the importance of neuroradiological examination in adult patients with the first epileptic seizure but with no focal neurological signs. .

Combined Effects of Feedforward Inhibition and Excitation in Thalamocortical Circuit on the Transitions of Epileptic Seizures

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Fan, Denggui; Duan, Lixia; Wang, Qian; Luan, Guoming

2017-01-01

The mechanisms underlying electrophysiologically observed two-way transitions between absence and tonic-clonic epileptic seizures in cerebral cortex remain unknown. The interplay within thalamocortical network is believed to give rise to these epileptic multiple modes of activity and transitions between them. In particular, it is thought that in some areas of cortex there exists feedforward inhibition from specific relay nucleus of thalamus (TC) to inhibitory neuronal population (IN) which has even more stronger functions on cortical activities than the known feedforward excitation from TC to excitatory neuronal population (EX). Inspired by this, we proposed a modified computational model by introducing feedforward inhibitory connectivity within thalamocortical circuit, to systematically investigate the combined effects of feedforward inhibition and excitation on transitions of epileptic seizures. We first found that the feedforward excitation can induce the transition from tonic oscillation to spike and wave discharges (SWD) in cortex, i.e., the epileptic tonic-absence seizures, with the fixed weak feedforward inhibition. Thereinto, the phase of absence seizures corresponding to strong feedforward excitation can be further transformed into the clonic oscillations with the increasing of feedforward inhibition, representing the epileptic absence-clonic seizures. We also observed the other fascinating dynamical states, such as periodic 2/3/4-spike and wave discharges, reversed SWD and clonic oscillations, as well as saturated firings. More importantly, we can identify the stable parameter regions representing the tonic-clonic oscillations and SWD discharges of epileptic seizures on the 2-D plane composed of feedforward inhibition and excitation, where the physiologically plausible transition pathways between tonic-clonic and absence seizures can be figured out. These results indicate the functional role of feedforward pathways in controlling epileptic seizures and

Combined Effects of Feedforward Inhibition and Excitation in Thalamocortical Circuit on the Transitions of Epileptic Seizures

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Denggui Fan

2017-07-01

Full Text Available The mechanisms underlying electrophysiologically observed two-way transitions between absence and tonic-clonic epileptic seizures in cerebral cortex remain unknown. The interplay within thalamocortical network is believed to give rise to these epileptic multiple modes of activity and transitions between them. In particular, it is thought that in some areas of cortex there exists feedforward inhibition from specific relay nucleus of thalamus (TC to inhibitory neuronal population (IN which has even more stronger functions on cortical activities than the known feedforward excitation from TC to excitatory neuronal population (EX. Inspired by this, we proposed a modified computational model by introducing feedforward inhibitory connectivity within thalamocortical circuit, to systematically investigate the combined effects of feedforward inhibition and excitation on transitions of epileptic seizures. We first found that the feedforward excitation can induce the transition from tonic oscillation to spike and wave discharges (SWD in cortex, i.e., the epileptic tonic-absence seizures, with the fixed weak feedforward inhibition. Thereinto, the phase of absence seizures corresponding to strong feedforward excitation can be further transformed into the clonic oscillations with the increasing of feedforward inhibition, representing the epileptic absence-clonic seizures. We also observed the other fascinating dynamical states, such as periodic 2/3/4-spike and wave discharges, reversed SWD and clonic oscillations, as well as saturated firings. More importantly, we can identify the stable parameter regions representing the tonic-clonic oscillations and SWD discharges of epileptic seizures on the 2-D plane composed of feedforward inhibition and excitation, where the physiologically plausible transition pathways between tonic-clonic and absence seizures can be figured out. These results indicate the functional role of feedforward pathways in controlling epileptic

Epileptic Seizures are Reduced by Autonomic Biofeedback Therapy Through Enhancement of Fronto-limbic Connectivity: A Controlled Trial and Neuroimaging Study

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Yoko Nagai

2018-01-01

Interpretation: Our clinical study provides evidence for autonomic biofeedback therapy as an effective and potent behavioral intervention for patients with drug-resistant epilepsy. This approach is non-pharmacological, non-invasive and seemingly side-effect free.

The Socio-Demographic and Clinical Characteristics of the Adult Epileptic Patients Applying to the Neurology Clinic of Erciyes University and the Relation of These Phenomena to Depression

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Vesile Şenol

2007-08-01

Full Text Available OBJECTIVE: The epidemiological characteristics of epilepsy vary from society to society. Epilepsy, whose prevalence is between 0.5-1.0%, is usually seen in early and late ages, at the both of ends of life, and more often in males, and in people who have low income and education. Besides ıts neuropsychologic effects, epilepsy is a disease which has psychological, socilogical aspects such as social isolation, low self-esteem and depression. Depression is seen more often in people with epilepsy than people who don’t have this disease. The percentage of depression for the whole life-time for people with epilepsy is 10-30%. Age at onset of epilepsy, seizure type, frequency, time and the type of treatment (mono-poly therapy affect the incidence and degree of depression. OBJECTIVES: To define the socio-demographic and clinical characteristics of epilepsy cases, to determine the percentage of depressive disorders in epilepsy cases, to probe the characteristics of epileptic seizure and its relation to depression. METHODS: The study was conducted through a face-to-face survey of 102 adult epileptic patients who applied to the Erciyes University Epilepsy Outpatient Clinic between October 2004 and 2005. In order to gather the data, which was prepared by the researcher “A survey form for the epileptic individuals” and “The Turkish Version of Beck Depression Inventory”, whose accuracy and validity was checked by Hisli, was used. RESULTS: The average age for the cases is 34.3±12.6, the average age at seizure onset is 21.4±14.6 and in 66% of them the seizure started when they were under 25. Majority of the cases were male and lower than the minimum wage. Among the patients, 45.6% had generalized (tonic-clonic seizures, and 36% had been ≥1/month seizures and 32% seizure-free during the previous year. CONCLUSION: The average of depressive disorder was 29.4%. 15.7% of the cases were with major depression. Age at onset epilepsy, seizure type and

High-Definition transcranial direct current stimulation in early onset epileptic encephalopathy: a case study.

Science.gov (United States)

Meiron, Oded; Gale, Rena; Namestnic, Julia; Bennet-Back, Odeya; David, Jonathan; Gebodh, Nigel; Adair, Devin; Esmaeilpour, Zeinab; Bikson, Marom

2018-01-01

Early onset epileptic encephalopathy is characterized by high daily seizure-frequency, multifocal epileptic discharges, severe psychomotor retardation, and death at infancy. Currently, there are no effective treatments to alleviate seizure frequency and high-voltage epileptic discharges in these catastrophic epilepsy cases. The current study examined the safety and feasibility of High-Definition transcranial direct current stimulation (HD-tDCS) in reducing epileptiform activity in a 30-month-old child suffering from early onset epileptic encephalopathy. HD-tDCS was administered over 10 intervention days spanning two weeks including pre- and post-intervention video-EEG monitoring. There were no serious adverse events or side effects related to the HD-tDCS intervention. Frequency of clinical seizures was not significantly reduced. However, interictal sharp wave amplitudes were significantly lower during the post-intervention period versus baseline. Vital signs and blood biochemistry remained stable throughout the entire study. These exploratory findings support the safety and feasibility of 4 × 1 HD-tDCS in early onset epileptic encephalopathy and provide the first evidence of HD-tDCS effects on paroxysmal EEG features in electroclinical cases under the age of 36 months. Extending HD-tDCS treatment may enhance electrographic findings and clinical effects.

Inferences from a community study about non-epileptic events

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Gomes Marleide da Mota

2002-01-01

Full Text Available OBJECTIVE: To demonstrate the epidemiological importance of the different types of non-epileptic events (NEE in a low-income urban community. METHOD: The patients suspected of having epilepsy, who were detected in the first phase (screening one of this prevalence study, were interviewed by a neurologist in a non-structured neurological interview. These NEE were classified as physiological and psychogenic, subdivided by various types. The psychogenic NEE were classified according to the DSM-IV criteria. RESULTS: We compared the cases suspected of having epilepsy (n=176 with those not suspected (n=806 and discovered that those cases suspected of having epilepsy had a greater median age (<0.01 and female predominance (p<0.01. Among the cases suspected of having epilepsy there were different diagnosis: epileptic events without identifiable cause (n=20 or with identifiable causes (e.g., febrile convulsions and eclampsia. The most prevalent diagnosis for those suspected of having epilepsy was syncope (n=63; 35.8%. In terms of physiological events, the most frequent were: epileptic seizures, paroxysmal toxic phenomena (including alcoholism and brain trauma, besides syncope; in terms of psychogenic events the most frequent were: dissociative and anxiety disorders. Regarding gender differences, paroxysmal toxic problems were significantly more prevalent in men (p= 0.02, and dissociative disorders (p=0.01 in women. CONCLUSION: This survey confirms the epidemiological importance of syncope in a populational sample with NEE. However, among the psychogenic disorders of this NEE sample, the most frequent were dissociative and anxiety phenomena. This finding contrasts with the literature based on samples from tertiary epileptic centers with video-EEG resources, which found somatoform disorders to be more prevalent than dissociative and anxiety phenomena.

Transplantation of bone marrow mononuclear cells modulates hippocampal expression of growth factors in chronically epileptic animals.

Science.gov (United States)

Zanirati, Gabriele; Azevedo, Pamella Nunes; Marinowic, Daniel Rodrigo; Rodrigues, Felipe; de Oliveira Dias, Ana Christina; Venturin, Gianina Teribele; Greggio, Samuel; Simão, Fabrício; DaCosta, Jaderson Costa

2015-05-01

In previous studies, transplantation of bone marrow mononuclear cells (BMMCs) in epileptic animals has been found to be neuroprotective. However, the mechanism by which the BMMCs act remains unclear. We hypothesize that BMMCs may provide neuroprotection to the epileptic brain through trophic support. To test our hypothesis, we studied the temporal expression of neurotrophins after BMMC transplantation in the epileptic rat hippocampus. Chronically epileptic rats were intravenously transplanted with 1 × 10(7) BMMCs isolated from GFP transgenic mice. Expression levels of BDNF, GDNF, NGF, VEGF, and TGF-β1, and their receptors, were evaluated by ELISA and/or qRT-PCR analysis. Our data revealed increased protein expression of BDNF, GDNF, NGF, and VEGF and reduced levels of TGF-β1 in the hippocampus of transplanted epileptic animals. Additionally, an increase in the mRNA expression of BDNF, GDNF, and VEGF, a reduction in TGF-β1, and a decrease in mRNA levels of the TrkA and TGFR-β1 receptors were also observed. The gain provided by transplanted BMMCs in the epileptic brain may be related to the ability of these cells in modulating the network of neurotrophins and angiogenic signals. © 2015 John Wiley & Sons Ltd.

Cardiac troponin I (CTnI level among children with epileptic seizures

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Ahmed Anwer Attia Khattab

2014-09-01

Conclusion: Cardiac troponin I is a perfect tool for early detection of cases with myocardial dysfunction in epileptic patients – cardiac troponin I is significantly increased in children with epilepsy especially the complicated epilepsy. Cardiac injury in epileptic children is more common in patients with early onset epilepsy, positive prenatal problem, idiopathic epilepsy, abnormal imaging and EEG – elevated TnI levels may be of value in assessing the severity and eventual outcome and mortality risk of the disease in children with epilepsy.

Differential DNA methylation patterns define status epilepticus and epileptic tolerance.

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Miller-Delaney, Suzanne F C; Das, Sudipto; Sano, Takanori; Jimenez-Mateos, Eva M; Bryan, Kenneth; Buckley, Patrick G; Stallings, Raymond L; Henshall, David C

2012-02-01

Prolonged seizures (status epilepticus) produce pathophysiological changes in the hippocampus that are associated with large-scale, wide-ranging changes in gene expression. Epileptic tolerance is an endogenous program of cell protection that can be activated in the brain by previous exposure to a non-harmful seizure episode before status epilepticus. A major transcriptional feature of tolerance is gene downregulation. Here, through methylation analysis of 34,143 discrete loci representing all annotated CpG islands and promoter regions in the mouse genome, we report the genome-wide DNA methylation changes in the hippocampus after status epilepticus and epileptic tolerance in adult mice. A total of 321 genes showed altered DNA methylation after status epilepticus alone or status epilepticus that followed seizure preconditioning, with >90% of the promoters of these genes undergoing hypomethylation. These profiles included genes not previously associated with epilepsy, such as the polycomb gene Phc2. Differential methylation events generally occurred throughout the genome without bias for a particular chromosomal region, with the exception of a small region of chromosome 4, which was significantly overrepresented with genes hypomethylated after status epilepticus. Surprisingly, only few genes displayed differential hypermethylation in epileptic tolerance. Nevertheless, gene ontology analysis emphasized the majority of differential methylation events between the groups occurred in genes associated with nuclear functions, such as DNA binding and transcriptional regulation. The present study reports select, genome-wide DNA methylation changes after status epilepticus and in epileptic tolerance, which may contribute to regulating the gene expression environment of the seizure-damaged hippocampus.

Novel Drug Delivery Technique for Breast Cancer Therapy

National Research Council Canada - National Science Library

Esenaliev, Rinat O

2004-01-01

.... We proposed to complete Task 3 and to implement Task 4 in the third year of the project. Task 3 focuses on in vivo studies of efficacy of cancer therapy with the use of ultrasound-enhanced delivery of anti-cancer drug 5-FU...

Cancer therapy with drug loaded magnetic nanoparticles-magnetic drug targeting

International Nuclear Information System (INIS)

Alexiou, Christoph; Tietze, Rainer; Schreiber, Eveline; Jurgons, Roland; Richter, Heike; Trahms, Lutz; Rahn, Helene; Odenbach, Stefan; Lyer, Stefan

2011-01-01

The aim of magnetic drug targeting (MDT) in cancer therapy is to concentrate chemotherapeutics to a tumor region while simultaneously the overall dose is reduced. This can be achieved with coated superparamagnetic nanoparticles bound to a chemotherapeutic agent. These particles are applied intra arterially close to the tumor region and focused to the tumor by a strong external magnetic field. The interaction of the particles with the field gradient leads to an accumulation in the region of interest (i.e. tumor). The particle enrichment and thereby the drug-load in the tumor during MDT has been proven by several analytical and imaging methods. Moreover, in pilot studies we investigated in an experimental in vivo tumor model the effectiveness of this approach. Complete tumor regressions without any negative side effects could be observed. - Research Highlights: →Iron oxide nanoparticles can be enriched in tumors by external magnetic fields. → Histology evidences the intravasation of particles enter the intracellular space. → Non-invasive imaging techniques can display the spatial arrangement of particles. → HPLC-analysis show outstanding drug enrichment in tumors after MDT.

Cancer therapy with drug loaded magnetic nanoparticles-magnetic drug targeting

Energy Technology Data Exchange (ETDEWEB)

Alexiou, Christoph, E-mail: c.alexiou@web.d [Department of Oto-rhino-laryngology, Head and Neck Surgery, University Hospital Erlangen, Section for Experimental Oncology and Nanomedicine at the Else Kroener-Fresenius-Stiftung-Professorship (Germany); Tietze, Rainer; Schreiber, Eveline [Department of Oto-rhino-laryngology, Head and Neck Surgery, University Hospital Erlangen, Section for Experimental Oncology and Nanomedicine at the Else Kroener-Fresenius-Stiftung-Professorship (Germany); Jurgons, Roland [Franz Penzoldt Center, University Hospital Erlangen (Germany); Richter, Heike; Trahms, Lutz [PTB Berlin (Germany); Rahn, Helene; Odenbach, Stefan [TU Dresden, Chair of Magnetofluiddynamics, 01062 Dresden (Germany); Lyer, Stefan [Department of Oto-rhino-laryngology, Head and Neck Surgery, University Hospital Erlangen, Section for Experimental Oncology and Nanomedicine at the Else Kroener-Fresenius-Stiftung-Professorship (Germany)

2011-05-15

The aim of magnetic drug targeting (MDT) in cancer therapy is to concentrate chemotherapeutics to a tumor region while simultaneously the overall dose is reduced. This can be achieved with coated superparamagnetic nanoparticles bound to a chemotherapeutic agent. These particles are applied intra arterially close to the tumor region and focused to the tumor by a strong external magnetic field. The interaction of the particles with the field gradient leads to an accumulation in the region of interest (i.e. tumor). The particle enrichment and thereby the drug-load in the tumor during MDT has been proven by several analytical and imaging methods. Moreover, in pilot studies we investigated in an experimental in vivo tumor model the effectiveness of this approach. Complete tumor regressions without any negative side effects could be observed. - Research Highlights: Iron oxide nanoparticles can be enriched in tumors by external magnetic fields. Histology evidences the intravasation of particles enter the intracellular space. Non-invasive imaging techniques can display the spatial arrangement of particles. HPLC-analysis show outstanding drug enrichment in tumors after MDT.

Depression and anxiety disorder among epileptic people at Amanuel Specialized Mental Hospital, Addis Ababa, Ethiopia.

Science.gov (United States)

Tegegne, Minale Tareke; Mossie, Tilahun Belete; Awoke, Andargie Abate; Assaye, Ashagre Molla; Gebrie, Belete Temitm; Eshetu, Desalegn Asmare

2015-09-02

Although depression and anxiety disorders are very common in people with epilepsy; there are no studies that assessed the magnitude and associated factors among epileptic people in Ethiopia. Therefore, this study determined prevalence and associated factors of depression and anxiety disorders in people with epilepsy. An institution based cross-sectional study was conducted from April to May, 2013, among 423 people with epilepsy from the outpatient department of Amanuel Mental Specialized Hospital. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale. Logistic regression analysis was used to assess predictors of depression and anxiety. The prevalence of anxiety and depression among epileptic people were 33.5 and 32.8%, respectively. Monthly income, frequency of seizure and side effects of anti convulsants were found to be significantly associated with both depression and anxiety. Being divorced/widowed was associated with anxiety while using poly-therapy of anti convulsants, perceived stigma, and inability to read or write were associated with depression. The prevalence of co-morbid anxiety and depression was found to be high among people with epilepsy. Early identification of co-morbid depression and anxiety in people with epilepsy and managing epilepsy to become seizure free should be of great concern for health care providers.

Family Therapy for Drug Abuse: Review and Updates 2003-2010

Science.gov (United States)

Rowe, Cynthia L.

2012-01-01

Just 15 years ago, Liddle and Dakof ("Journal of Marital and Family Therapy," 1995; 21, 511) concluded, based on the available evidence, that family therapy represented a "promising, but not definitive" approach for the treatment of drug problems among adolescents and adults. Seven years later, Rowe and Liddle (2003) review described considerable…

Genetics Home Reference: early infantile epileptic encephalopathy 1

Science.gov (United States)

... Early infantile epileptic encephalopathy 1 (EIEE1) is a seizure disorder characterized by a type of seizure known as ... 2 links) Health Topic: Developmental Disabilities Health Topic: Epilepsy Genetic and Rare Diseases Information Center (1 link) ...

Self-assembled nanoparticles based on PEGylated conjugated polyelectrolyte and drug molecules for image-guided drug delivery and photodynamic therapy.

Science.gov (United States)

Yuan, Youyong; Liu, Bin

2014-09-10

A drug delivery system based on poly(ethylene glycol) (PEG) grafted conjugated polyelectrolyte (CPE) has been developed to serve as a polymeric photosensitizer and drug carrier for combined photodynamic and chemotherapy. The amphiphilic brush copolymer can self-assemble into micellar nanopaticles (NPs) in aqueous media with hydrophobic conjugated polyelectrolyte backbone as the core and hydrophilic PEG as the shell. The NPs have an average diameter of about 100 nm, with the absorption and emission maxima at 502 and 598 nm, respectively, making them suitable for bioimaging applications. Moreover, the CPE itself can serve as a photosensitizer, which makes the NPs not only a carrier for drug but also a photosensitizing unit for photodynamic therapy, resulting in the combination of chemo- and photodynamic therapy for cancer. The half-maximal inhibitory concentration (IC50) value for the combination therapy to U87-MG cells is 12.7 μg mL(-1), which is much lower than that for the solely photodynamic therapy (25.5 μg mL(-1)) or chemotherapy (132.8 μg mL(-1)). To improve the tumor specificity of the system, cyclic arginine-glycine-aspartic acid (cRGD) tripeptide as the receptor to integrin αvβ3 overexpressed cancer cells was further incorporated to the surface of the NPs. The delivery system based on PEGylated CPE is easy to fabricate, which integrates the merits of targeted cancer cell image, chemotherapeutic drug delivery, and photodynamic therapy, making it promising for cancer treatment.

Microwave coagulation therapy and drug injection to treat splenic injury.

Science.gov (United States)

Zhang, Guoming; Sun, Yuanyuan; Yu, Jie; Dong, Lei; Mu, Nannan; Liu, Xiaohong; Liu, Lanfen; Zhang, Yan; Wang, Xiaofei; Liang, Ping

2014-01-01

The present study compares the efficacy of 915- and 2450-MHz contrast-enhanced ultrasound (CEUS)-guided percutaneous microwave coagulation with that of CEUS-guided thrombin injection for the treatment of trauma-induced spleen hemorrhage. In a canine splenic artery hemorrhage model with two levels of arterial diameter (A, microwaves and drug injection. Therapy efficacy was measured by comparing bleeding rate, hemostatic time, bleeding index, bleeding volume, and pathology. The most efficient technique was CEUS-guided 915-MHz percutaneous microwave coagulation therapy in terms of action time and total blood loss. The success rate of the 915-MHz microwave group was higher than that of the 2450-MHz microwave and the drug injection groups (except A level, P microwave group than those in the 2450-MHz microwave and drug injection groups (P microwave group, but pathologic changes of light injury could be seen in the other groups. The present study provides evidence that microwave coagulation therapy is more efficient than thrombin injection for the treatment of splenic hemorrhage. Furthermore, treatment with 915-MHz microwaves stops bleeding more rapidly and generates a wider cauterization zone than does treatment with 2450-MHz microwaves. Copyright © 2014 Elsevier Inc. All rights reserved.

The clinical presentation and diagnosis of epileptic autonomic auras

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Marina Revditovna Kremenchugskaya

2012-01-01

Full Text Available Objective: to refine the pattern of clinical manifestations of epileptic autonomic auras (EAA and to reveal clinical, electroencephalographic, and neuroimaging ratios. Patients and methods. Eighteen patients (8, 41% men and 10, 59% women aged 9 to 27years (mean 18±5years were examined. The examination encompassed analysis of history data, clinical and neurological studies, long-term video-assisted electroencephalographic monitoring, and magnetic resonance imaging (MRI of the brain. Results. In most patients (n = 12, 67%, the symptoms of EAA corresponded to the criteria for abdominal one. In the other patients, the clinical manifestations resembled autonomic paroxysms as attacks of panic. Interictal pathological changes on an electroencephalogram (EEG were present in the frontal, temporal, and frontotemporal regions in 4 (22%, 6 (33%, and 7 (39% patients, respectively, as well as in both the left and right hemispheres without significant differences. Pathological EEG changes were not found in one case. MRI detected that 13 (72% patients had structural changes that were potentially eliptogenic. Conclusion. The clinical symptoms of EAA give information on the site of a primary pathological focus. It is necessary to differentiate EAA from non-epileptic paroxysmal states. The autonomic phenomena of epileptic genesis help study the functional organizations of the autonomic nervous system.

Nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs.

Science.gov (United States)

Huang, Wei; Chen, Liqing; Kang, Lin; Jin, Mingji; Sun, Ping; Xin, Xin; Gao, Zhonggao; Bae, You Han

2017-06-01

Anticancer therapy has always been a vital challenge for the development of nanomedicine. Repeated single therapeutic agent may lead to undesirable and severe side effects, unbearable toxicity and multidrug resistance due to complex nature of tumor. Nanomedicine-based combination anticancer therapy can synergistically improve antitumor outcomes through multiple-target therapy, decreasing the dose of each therapeutic agent and reducing side effects. There are versatile combinational anticancer strategies such as chemotherapeutic combination, nucleic acid-based co-delivery, intrinsic sensitive and extrinsic stimulus combinational patterns. Based on these combination strategies, various nanocarriers and drug delivery systems were engineered to carry out the efficient co-delivery of combined therapeutic agents for combination anticancer therapy. This review focused on illustrating nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs for synergistically improving anticancer efficacy. Copyright © 2017 Elsevier B.V. All rights reserved.

CDKL5 gene-related epileptic encephalopathy: electroclinical findings in the first year of life.

Science.gov (United States)

Melani, Federico; Mei, Davide; Pisano, Tiziana; Savasta, Salvatore; Franzoni, Emilio; Ferrari, Anna Rita; Marini, Carla; Guerrini, Renzo

2011-04-01

Cyclin-dependent kinase-like 5 (CDKL5) gene abnormalities cause an early-onset epileptic encephalopathy. We performed video-electroencephalography (video-EEG) monitoring early in the course of CDKL5-related epileptic encephalopathy in order to examine the early electroclinical characteristics of the condition. We used video-EEG to monitor six infants (five females, one male) with CDKL5-related epileptic encephalopathy (five mutations; one deletion), at ages 45 days to 12 months and followed them up to the ages of 14 months to 5 years (mean age 23 mo). We focused our analysis on the first year of life. The results were evaluated against those of a comparison group of nine infants (aged below 1y) with epileptic encephalography who had tested negative for CDKL5 mutations and deletions. One infant exhibited normal background activity, three exhibited moderate slowing, and two exhibited a suppression burst pattern. Two participants had epileptic spasms and four had a stereotyped complex seizure pattern, which we defined as a 'prolonged' generalized tonic-clonic event consisting of a tonic-tonic/vibratory contraction, followed by a clonic phase with series of spasms, gradually translating into repetitive distal myoclonic jerks. Seizure duration ranged from 2 to 4 minutes. The EEG correlate of each clinical phase included an initial electrodecremental event (tonic vibratory phase), irregular series of sharp waves and spike slow waves (clonic phase with series of spasms), and bilateral rhythmic sharp waves (time locked with myoclonus). Infants with CDKL5-related early epileptic encephalopathy can present in the first year of life with an unusual electroclinical pattern of 'prolonged' generalized tonic-clonic seizures. © The Authors. Journal compilation © Mac Keith Press 2011.

Epileptic aura and perception of self-control

DEFF Research Database (Denmark)

Lohse, Allan; Kjaer, Troels W; Sabers, Anne

2015-01-01

OBJECTIVE: The health locus of control is the subjective perception of control over one's health. It has been studied for years as one of several factors that determine patient health-related behaviors. The aim of this study was to investigate how the epileptic aura is associated with the health...

Potential drug interactions in patients given antiretroviral therapy.

Science.gov (United States)

Santos, Wendel Mombaque Dos; Secoli, Silvia Regina; Padoin, Stela Maris de Mello

2016-11-21

to investigate potential drug-drug interactions (PDDI) in patients with HIV infection on antiretroviral therapy. a cross-sectional study was conducted on 161 adults with HIV infection. Clinical, socio demographic, and antiretroviral treatment data were collected. To analyze the potential drug interactions, we used the software Micromedex(r). Statistical analysis was performed by binary logistic regression, with a p-value of ≤0.05 considered statistically significant. of the participants, 52.2% were exposed to potential drug-drug interactions. In total, there were 218 potential drug-drug interactions, of which 79.8% occurred between drugs used for antiretroviral therapy. There was an association between the use of five or more medications and potential drug-drug interactions (p = 0.000) and between the time period of antiretroviral therapy being over six years and potential drug-drug interactions (p central nervous and cardiovascular systems, but also can interfere in tests used for detection of HIV resistance to antiretroviral drugs. investigar potenciais interações droga-droga (PDDI) em pacientes infectados com HIV em terapia de antirretroviral. um estudo de corte transversal foi conduzido em 161 pessoas infectadas com o HIV. Dados de tratamentos clínicos, sociodemográficos e antirretrovirais foram coletados. Para analisar a possível interação medicamentosa, nós usamos o software Micromedex(r). A análise estatística foi feita por regressão logística binária, com um valor P de ≤0.05, considerado estatisticamente significativo. dos participantes, 52.2% foram expostos a potenciais interações droga-droga. No total, houve 218 interações droga-droga, das quais 79.8% ocorreram entre drogas usadas para a terapia antirretroviral. Houve uma associação entre o uso de cinco ou mais medicamentos e possíveis interações droga-droga (p = 0.000), e entre o período de tempo de terapia antirretroviral acima de seis anos e possíveis interações droga

Application of rare variant transmission disequilibrium tests to epileptic encephalopathy trio sequence data

DEFF Research Database (Denmark)

2017-01-01

The classic epileptic encephalopathies, including infantile spasms (IS) and Lennox-Gastaut syndrome (LGS), are severe seizure disorders that usually arise sporadically. De novo variants in genes mainly encoding ion channel and synaptic proteins have been found to account for over 15% of patients...... with IS or LGS. The contribution of autosomal recessive genetic variation, however, is less well understood. We implemented a rare variant transmission disequilibrium test (TDT) to search for autosomal recessive epileptic encephalopathy genes in a cohort of 320 outbred patient-parent trios that were generally...... not find evidence of a role for individual autosomal recessive genes, our current sample is insufficiently powered to assess the overall role of autosomal recessive genotypes in an outbred epileptic encephalopathy population....

The lateralizing and localizing value of peri-ictal cough in epileptic seizures

OpenAIRE

Korkmaz, Bektaş; Erşen, Gülsün; Delil, Şakir; Özkara, Çiğdem; Yeni, S. Naz

2013-01-01

Introduction. Coughing may be observed as an epiphenomenon during or after epileptic seizures. Aim. In this paper we discuss the lateralization and localization value of cough as an epileptic peri/post ictal semiological phenomenon. Material and Methods. Seven patients presenting cough as a part of their symptomatology are presented. We will discuss cough in the context of these seven patients. Results. Six out of these seven patients were multidrug resistant temporal lobe epilepsy patient...

‘Transient epileptic amnesia’ : een caus en loteratuuroverzicht

NARCIS (Netherlands)

Thissen, S.; Vlooswijk, Marielle; Hendriks, M.P.H.; Majoie, Marian

‘Transient epileptic amnesia’ (TEA) wordt gezien als een weinig voorkomende vorm van temporaalkwabepilepsie, gekarakteriseerd door aanvallen van specifieke amnesie door epileptische activiteit (ictaalof postictaal). TEA treft voornamelijk mannen bovende 40 jaar. Aanvallen duren korter dan 60 minuten

Competence of medical students in communicating drug therapy: Value of role-play demonstrations.

Science.gov (United States)

Tayem, Yasin I; Altabtabaei, Abdulaziz S; Mohamed, Mohamed W; Arrfedi, Mansour M; Aljawder, Hasan S; Aldebous, Fahad A; James, Henry; Al Khaja, Khalid A J; Sequeira, Reginald P

2016-01-01

This study used role-play demonstrations to train medical students to communicate drug therapy and evaluated the perceptions on this instructional approach. The second-year medical students who attended a prescription writing session (n = 133), participated in this study. Prescription communication was introduced by using role-play demonstrations. Participant's perceptions were explored by a self-administered questionnaire and focus group discussion. The academic achievement of attendees and nonattendees was compared with an objective structured performance evaluation (OSPE) station that tested students' competence in this skill. Most attendees responded to the questionnaire (81.2%). Almost all respondents expressed their desire to have similar demonstrations in other units. A large proportion of participants reported that role-play demonstrations helped them develop their communication skills, in general, confidence to communicate drug-related information in a prescription, and the ability to explain the aim of drug therapy to patients. Most trainees thought also that they developed skills to communicate instructions on drug use including drug dose, frequency of administration, duration of therapy, adverse drug reactions, and warnings. During the focus group interviews, students thought that role-play was useful but would be more beneficial if conducted frequently in small group as part of the curriculum implementation. The majority of students also reported improved competence in writing a complete prescription. Analysis of attendees and nonattendees grades in the OSPE showed that the former scored higher than the latter group (P = 0.016). Role-play demonstrations were well accepted by medical students and led to the development of their competence in communicating drug therapy to patients.

Drug addiction therapy. A dance to the music of time.

Science.gov (United States)

Goodison, L; Schafer, H

1999-10-21

Dance therapy can play a useful role in the treatment and rehabilitation of women with drug addiction. It works by raising self-esteem through an improved relationship with the body, giving women the strength to help combat their habit. The benefits of dance therapy for women at the detox unit of Holloway Prison have been confirmed by prison staff.

CDKL5 alterations lead to early epileptic encephalopathy in both genders.

Science.gov (United States)

Liang, Jao-Shwann; Shimojima, Keiko; Takayama, Rumiko; Natsume, Jun; Shichiji, Minobu; Hirasawa, Kyoko; Imai, Kaoru; Okanishi, Tohru; Mizuno, Seiji; Okumura, Akihisa; Sugawara, Midori; Ito, Tomoshiro; Ikeda, Hiroko; Takahashi, Yukitoshi; Oguni, Hirokazu; Imai, Katsumi; Osawa, Makiko; Yamamoto, Toshiyuki

2011-10-01

Genetic mutations of the cyclin-dependent kinase-like 5 gene (CDKL5) have been reported in patients with epileptic encephalopathy, which is characterized by intractable seizures and severe-to-profound developmental delay. We investigated the clinical relevance of CDKL5 alterations in both genders. A total of 125 patients with epileptic encephalopathy were examined for genomic copy number aberrations, and 119 patients with no such aberrations were further examined for CDKL5 mutations. Five patients with Rett syndrome, who did not show methyl CpG-binding protein 2 gene (MECP2) mutations, were also examined for CDKL5 mutations. One male and three female patients showed submicroscopic deletions including CDKL5, and two male and six female patients showed CDKL5 nucleotide alterations. Development of early onset seizure was a characteristic clinical feature for the patients with CDKL5 alterations in both genders despite polymorphous seizure types, including myoclonic seizures, tonic seizures, and spasms. Severe developmental delays and mild frontal lobe atrophies revealed by brain magnetic resonance imaging (MRI) were observed in almost all patients, and there was no gender difference in phenotypic features. We observed that 5% of the male patients and 14% of the female patients with epileptic encephalopathy had CDKL5 alterations. These findings indicate that alterations in CDKL5 are associated with early epileptic encephalopathy in both female and male patients. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

Clinical and electroencephalographic characteristics of some forms of epileptic encephalopathies in infants: The data of the authors' follow-up observations

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I. D. Lemeshko

2016-01-01

Full Text Available Objective: to study clinical symptoms and brain activity in new forms of infantile epilepsy, such as malignant migrating partial seizures in infancy (MMPSI and Markand-Blume-Ohtahara syndrome (MBOS and to elaborate their differential diagnostic criteria for the timely choice of treatment policy and for the prediction of the disease.Patients and methods. Thirty-eight children aged 1.5 months to 3 years with MMPSI and MBOS were examined. Their medical history and neurological examination data, electroencephalographic and neuroimaging characteristics, and the efficiency of chosen anticonvulsant therapy were investigated.Results and discussion. The investigators revealed the following characteristics of these forms: the causes of these syndromes were highly diverse and unspecific; the neurological status was characterized by a variety of symptoms with an obvious delay in psycho-prespeech development concurrent with a high rate of partial focal (in MMPSI and generalized (in MBOS status epilepticus; The EEC characteristic sign was MISF and«lafa» patterns in the children with MBOS and continuous migrating partial ictal status epilepticus patterns in those with MMPSI. These forms of epileptic encephalopathies are extremely drug-resistant and characterized by a high risk for a fatal outcome.

Enhancing the Pediatric Drug Development Framework to Deliver Better Pediatric Therapies Tomorrow.

Science.gov (United States)

Bucci-Rechtweg, Christina

2017-10-01

Health care professionals involved in the clinical management of children have long appreciated the limited number of therapies suitably evaluated for their optimal use in the pediatric population. In the past century, advances in regulatory policy significantly evolved adult drug evaluation. The scarcity of available patient populations, practical complexities of drug development research, and minimal financial returns have hampered pharmaceutical investment in the study of therapies for children. More recently, pediatric policy and legislation in the United States and Europe have instituted a system of obligations and incentives to stimulate investment in pediatric drug development. These initiatives, in conjunction with a more sophisticated process of drug discovery and development, have led to significant advancements in the labeling of drugs for pediatric use. Facilitated by the emergence of new targets, precision medicine, and innovations in regulatory science, there is now a subtle shift in focus toward drug development research for children rather than simply in children. Although there has been an increase in pediatric studies of investigational agents and labeling of pediatric information for use, there have been unintended consequences of existing policies. As a result, limited progress has been made in certain therapeutic areas and for off-patent therapies. Future policy reform to enhance the availability and accessibility of pediatric medicines should not only reflect an understanding not only of the successes of existing policy and legislative initiatives but also constructively address failures and unintended consequences. Taken together, policy reform, global cooperation, and innovation in regulatory science will more ably deliver better pediatric therapies tomorrow. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Application of magnetic source imaging in localizing the epileptic foci in patients with grey matter heterotopia

International Nuclear Information System (INIS)

Sun Jilin; Wu Jie; Jia Xiuchuan; Li Sumin

2011-01-01

Objective: To evaluate the value of magnetic source imaging (MSI) in localizing the epileptic foci of patients with histologically proved grey matter heterotopia (GMH) and seizure. Methods: MSI examinations were performed on 8 patients with GMH and seizure. The location of the epileptic foci defined by MSI was compared with the results of the ECoG. After imaging examinations, all patients received operation with 13-48 months follow up to observe the effectiveness of the operation. Results: Among the 8 patients, 1 had hippocampal sclerosis, 2 had focal cortical dysplasia of type Ⅰ B and 1 had focal cortical dysplasia of type Ⅱ B. MRI showed normal findings in 2 cases, subcortical heterotopia in 4 cases, and nodular heterotopia in 2 cases with one having schizencephaly. The epileptic foci defined by MSI were at right temporal lobe in 2 cases, left frontal lobe in 2 cases, biparietal lobe in 1 case, left parietal lobe in 1 case, left temporal lobe in 1 case, and left frontal-parietal lobe in 1 case. The epileptic foci defined by MSI were completely overlaid with area of GMH in 4 cases, closely behind the area of GMH in case, and partly overlaid with area of CMH in 1 cases with size larger than that of the latter. One patient showed two epileptic foci with one located within the area of GMH and the other one 2 centimeters anterior to the area of GMH. One case's epileptic focus located 2 centimeters posteolateral to the area of GMH. The locations of the epileptic foci defined by MSI showed no difference with those defined by ECoG in all patients. According to Engel classification of treatment effect of epilepsy, 6 patients achieved Engle class Ⅰ ( seizure free after operation), and 2 patients Engel class Ⅳ (no changes in the frequency of occurrence of seizures before and after operation). Conclusion: MSI can noninvasively and precisely localize the epileptic foci before operation in patients with GMH and seizure. (authors)

Neo-Timm staining in the thalamus of chronically epileptic rats

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Hamani C.

2005-01-01

Full Text Available The thalamus is an important modulator of seizures and is severely affected in cholinergic models of epilepsy. In the present study, chronically epileptic rats had their brains processed for neo-Timm and acetylcholinesterase two months after the induction of status epilepticus with pilocarpine. Both controls and pilocarpine-treated animals presented neo-Timm staining in the anterodorsal nucleus, laterodorsal nucleus, reticular nucleus, most intralaminar nuclei, nucleus reuniens, and rhomboid nucleus of the thalamus, as well as in the zona incerta. The intensity of neo-Timm staining was similar in control and pilocarpine-treated rats, except for the nucleus reuniens and the rhomboid nucleus, which had a lower intensity of staining in the epileptic group. In animal models of temporal lobe epilepsy, zinc seems to modulate glutamate release and to decrease seizure activity. In this context, a reduction of neo-Timm-stained terminals in the midline thalamus could ultimately result in an increased excitatory activity, not only within its related nuclei, but also in anatomical structures that receive their efferent connections. This might contribute to the pathological substrate observed in chronic pilocarpine-treated epileptic animals.

Development of a neurostimulator for studies of epileptic crisis

International Nuclear Information System (INIS)

Niro, J; Manso, J; Ballina, F; Periolo, S; D'Atellis, C; Ponce, S; Barroso, M; Anessi, C; Kochen, S

2007-01-01

This work describes the development and use of a multi-channel, programmable physiological stimulator. The device is intended for the detection of epileptic events and crisis prediction using encephalograms. The animals were followed by the kindling model. The system program accepts several inputs of stimulation parameters such as, pulse width, separation between pulses, pulse intensity and total number of pulses. The stimulator generates constant-current, bipolar pulses with a maximum amplitude of 5 mA and a resolution of 50μA. As regards voltage, the maximum amplitude is 150 V. The stimulator was constructed with a microcontroller (PIC18F4550), the latter version being controlled by a personal computer. Experiments of achieving the epileptic events were carried out on rats

Development of a neurostimulator for studies of epileptic crisis

Energy Technology Data Exchange (ETDEWEB)

Niro, J [Universidad Tecnologica Nacional / Secretaria de Proyectos Especiales, Buenos Aires (Argentina); Manso, J [Universidad Tecnologica Nacional / Secretaria de Proyectos Especiales, Buenos Aires (Argentina); Ballina, F [Universidad Tecnologica Nacional / Secretaria de Proyectos Especiales, Buenos Aires (Argentina); Periolo, S [Universidad Tecnologica Nacional / Secretaria de Proyectos Especiales, Buenos Aires (Argentina); D' Atellis, C [Universidad Tecnologica Nacional / Secretaria de Proyectos Especiales, Buenos Aires (Argentina); Ponce, S [Universidad Tecnologica Nacional / Secretaria de Proyectos Especiales, Buenos Aires (Argentina); Barroso, M [Universidad Nacional de Buenos Aires / Facultad de Medicina, Centro de Epilepsia UBA - CONICET, Buenos Aires (Argentina); Anessi, C [Universidad Nacional de Buenos Aires / Facultad de Medicina, Centro de Epilepsia UBA - CONICET, Buenos Aires (Argentina); Kochen, S [Universidad Nacional de Buenos Aires / Facultad de Medicina, Centro de Epilepsia UBA - CONICET, Buenos Aires (Argentina)

2007-11-15

This work describes the development and use of a multi-channel, programmable physiological stimulator. The device is intended for the detection of epileptic events and crisis prediction using encephalograms. The animals were followed by the kindling model. The system program accepts several inputs of stimulation parameters such as, pulse width, separation between pulses, pulse intensity and total number of pulses. The stimulator generates constant-current, bipolar pulses with a maximum amplitude of 5 mA and a resolution of 50{mu}A. As regards voltage, the maximum amplitude is 150 V. The stimulator was constructed with a microcontroller (PIC18F4550), the latter version being controlled by a personal computer. Experiments of achieving the epileptic events were carried out on rats.

Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer therapy.

Science.gov (United States)

Dilnawaz, Fahima; Singh, Abhalaxmi; Mohanty, Chandana; Sahoo, Sanjeeb K

2010-05-01

The primary inadequacy of chemotherapeutic drugs is their relative non-specificity and potential side effects to the healthy tissues. To overcome this, drug loaded multifunctional magnetic nanoparticles are conceptualized. We report here an aqueous based formulation of glycerol monooleate coated magnetic nanoparticles (GMO-MNPs) devoid of any surfactant capable of carrying high payload hydrophobic anticancer drugs. The biocompatibility was confirmed by tumor necrosis factor alpha assay, confocal microscopy. High entrapment efficiency approximately 95% and sustained release of encapsulated drugs for more than two weeks under in vitro conditions was achieved for different anticancer drugs (paclitaxel, rapamycin, alone or combination). Drug loaded GMO-MNPs did not affect the magnetization properties of the iron oxide core as confirmed by magnetization study. Additionally the MNPs were functionalized with carboxylic groups by coating with DMSA (Dimercaptosuccinic acid) for the supplementary conjugation of amines. For targeted therapy, HER2 antibody was conjugated to GMO-MNPs and showed enhanced uptake in human breast carcinoma cell line (MCF-7). The IC(50) doses revealed potential antiproliferative effect in MCF-7. Therefore, antibody conjugated GMO-MNPs could be used as potential drug carrier for the active therapeutic aspects in cancer therapy. Copyright 2010 Elsevier Ltd. All rights reserved.

Weather as a risk factor for epileptic seizures: A case-crossover study.

Science.gov (United States)

Rakers, Florian; Walther, Mario; Schiffner, Rene; Rupprecht, Sven; Rasche, Marius; Kockler, Michael; Witte, Otto W; Schlattmann, Peter; Schwab, Matthias

2017-07-01

Most epileptic seizures occur unexpectedly and independently of known risk factors. We aimed to evaluate the clinical significance of patients' perception that weather is a risk factor for epileptic seizures. Using a hospital-based, bidirectional case-crossover study, 604 adult patients admitted to a large university hospital in Central Germany for an unprovoked epileptic seizure between 2003 and 2010 were recruited. The effect of atmospheric pressure, relative air humidity, and ambient temperature on the onset of epileptic seizures under temperate climate conditions was estimated. We found a close-to-linear negative correlation between atmospheric pressure and seizure risk. For every 10.7 hPa lower atmospheric pressure, seizure risk increased in the entire study population by 14% (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.01-1.28). In patients with less severe epilepsy treated with one antiepileptic medication, seizure risk increased by 36% (1.36, 1.09-1.67). A high relative air humidity of >80% increased seizure risk in the entire study population by up to 48% (OR 1.48, 95% CI 1.11-1.96) 3 days after exposure in a J-shaped association. High ambient temperatures of >20°C decreased seizure risk by 46% in the overall study population (OR 0.54, 95% CI 0.32-0.90) and in subgroups, with the greatest effects observed in male patients (OR 0.33, 95% CI 0.14-0.74). Low atmospheric pressure and high relative air humidity are associated with an increased risk for epileptic seizures, whereas high ambient temperatures seem to decrease seizure risk. Weather-dependent seizure risk may be accentuated in patients with less severe epilepsy. Our results require further replication across different climate regions and cohorts before reliable clinical recommendations can be made. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Profiling persistent tubercule bacilli from patient sputa during therapy predicts early drug efficacy.

Science.gov (United States)

Honeyborne, Isobella; McHugh, Timothy D; Kuittinen, Iitu; Cichonska, Anna; Evangelopoulos, Dimitrios; Ronacher, Katharina; van Helden, Paul D; Gillespie, Stephen H; Fernandez-Reyes, Delmiro; Walzl, Gerhard; Rousu, Juho; Butcher, Philip D; Waddell, Simon J

2016-04-07

New treatment options are needed to maintain and improve therapy for tuberculosis, which caused the death of 1.5 million people in 2013 despite potential for an 86 % treatment success rate. A greater understanding of Mycobacterium tuberculosis (M.tb) bacilli that persist through drug therapy will aid drug development programs. Predictive biomarkers for treatment efficacy are also a research priority. Genome-wide transcriptional profiling was used to map the mRNA signatures of M.tb from the sputa of 15 patients before and 3, 7 and 14 days after the start of standard regimen drug treatment. The mRNA profiles of bacilli through the first 2 weeks of therapy reflected drug activity at 3 days with transcriptional signatures at days 7 and 14 consistent with reduced M.tb metabolic activity similar to the profile of pre-chemotherapy bacilli. These results suggest that a pre-existing drug-tolerant M.tb population dominates sputum before and after early drug treatment, and that the mRNA signature at day 3 marks the killing of a drug-sensitive sub-population of bacilli. Modelling patient indices of disease severity with bacterial gene expression patterns demonstrated that both microbiological and clinical parameters were reflected in the divergent M.tb responses and provided evidence that factors such as bacterial load and disease pathology influence the host-pathogen interplay and the phenotypic state of bacilli. Transcriptional signatures were also defined that predicted measures of early treatment success (rate of decline in bacterial load over 3 days, TB test positivity at 2 months, and bacterial load at 2 months). This study defines the transcriptional signature of M.tb bacilli that have been expectorated in sputum after two weeks of drug therapy, characterizing the phenotypic state of bacilli that persist through treatment. We demonstrate that variability in clinical manifestations of disease are detectable in bacterial sputa signatures, and that the changing M.tb m

Tubulin Inhibitor-Based Antibody-Drug Conjugates for Cancer Therapy

Directory of Open Access Journals (Sweden)

Hao Chen

2017-08-01

Full Text Available Antibody-drug conjugates (ADCs are a class of highly potent biopharmaceutical drugs generated by conjugating cytotoxic drugs with specific monoclonal antibodies through appropriate linkers. Specific antibodies used to guide potent warheads to tumor tissues can effectively reduce undesired side effects of the cytotoxic drugs. An in-depth understanding of antibodies, linkers, conjugation strategies, cytotoxic drugs, and their molecular targets has led to the successful development of several approved ADCs. These ADCs are powerful therapeutics for cancer treatment, enabling wider therapeutic windows, improved pharmacokinetic/pharmacodynamic properties, and enhanced efficacy. Since tubulin inhibitors are one of the most successful cytotoxic drugs in the ADC armamentarium, this review focuses on the progress in tubulin inhibitor-based ADCs, as well as lessons learned from the unsuccessful ADCs containing tubulin inhibitors. This review should be helpful to facilitate future development of new generations of tubulin inhibitor-based ADCs for cancer therapy.

Etomidate accurately localizes the epileptic area in patients with temporal lobe epilepsy.

Science.gov (United States)

Pastor, Jesús; Wix, Rybel; Meilán, María Luisa; Martínez-Chacón, José Luís; de Dios, Eva; Domínguez-Gadea, Luis; Herrera-Peco, Iván; Sola, Rafael G

2010-04-01

A variety of drugs have been used to activate and identify the epileptogenic area in patients during presurgical evaluation. We have evaluated the safety and usefulness of etomidate in identifying the epileptic zone by measuring bioelectrical brain activity and cerebral blood flow (CBF). We studied 13 men and 9 women under presurgical evaluation for temporal lobe epilepsy. We applied etomidate (0.1 mg/kg) while patients were monitored by video-electroencephalography (VEEG) with foramen ovale electrodes. In a subset of 15 patients, we also measured CBF with single photon emission computed tomography (SPECT). (1) Etomidate induced seizures in 2 of 22 patients. (2) The main side-effects observed were myoclonus (14 of 20) and moderate pain (3 of 20). (3) No changes in capillary oxygen saturation, respiration, or heart rate were observed. (4) Irritative activity specifically increased in the temporal mesial and lateral areas. No spikes were observed in other areas, aside from those observed under baseline conditions. (5) Irritative activity induced by etomidate correctly lateralized the ictal onset zone in 19 of 20 patients. In addition, the two etomidate-induced seizures appeared in the same regions as spontaneous ones. (6) The kinetics of pharmacologically induced activity was higher in the region of the ictal-onset zone. (7) Etomidate increased the CBF in the basal ganglia and especially in the posterior hippocampus of the temporal mesial region contralateral to the ictal-onset zone. Etomidate activation is a safe, specific, and quick test that can be used to identify the epileptic region in patients evaluated as candidates for temporal lobe epilepsy surgery.

GRIN1 Mutations in Early-Onset Epileptic Encephalopathy

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Wenjuan Chen

2015-06-01

Full Text Available Investigators from Yokohama City University and other medical centers in Israel and Japan reported mutations on N-methyl-D-aspartate (NMDA receptors subunit GRIN1 (GluN1 identified in patients with nonsyndromic intellectual disability and early-onset epileptic encephalopathy.

[Combination drug therapy in patients with BPH].

Science.gov (United States)

Kuzmenko, A V; Kuzmenko, V V; Gyaurgiev, T A

2018-03-01

Introuction. One of the risk factors for LUTS is an infravesical obstruction, which is most often caused by benign prostatic hyperplasia (BPH). BPH symptoms are formed due to three components: static (mechanical), dynamic, and impaired functional capacity of the bladder. Medical treatment with 1-blockers decreases the outflow obstruction. 5-alpha reductase inhibitors are used to inhibit the static component of BPH. To investigate the effectiveness of various modifications of medical therapy of BPH using -blockers and 5-reductase inhibitors and combinations thereof. The study comprised 90 BPH patients who were divided into three groups, with each group containing 30 people. Patients of group I, II and III received monotherapy with -blockers, a combination of 5-reductase and -blockers, and fixed-dose combination drug Duodart, respectively. Evaluation of the treatment effectiveness included filling out voiding diaries, completing the I-PSS and QL questionnaires, uroflowmetry, transrectal ultrasonography of the prostate and estimation of the incidence of adverse effects. Also, compliance with the treatment was evaluated, and the number of patients who had episodes of acute urinary retention and required surgical treatment during the 12 month treatment course was registered. Compared to monotherapy, combination therapy with -blockers and 5-reductase inhibitors more effectively reduces the LUTS, increases Qmax and prevents the disease progression, which manifests in a lower incidence of AUR and fewer surgical interventions in groups II and III. However, the combination therapy can be associated with some side effects. Patients who received fixed-dose combination drug Duodart had a greater compliance rate than patients on the combination of drugs, which, in our opinion, is associated with fewer cases of AUR and surgical interventions. The use of Duodart in patients with BPH effectively alleviates LUTS and reduces the risk of the disease progression, which manifests itself

Treatment with antithyroid drugs or iodine following radioiodine therapy for Graves' disease

International Nuclear Information System (INIS)

Mazeto, Glaucia; Leal, B.M.B.; Souza, L.S.; Griva, B.L.; Moriguchi, S.M.; Moreira, C.C.; Lemos, A.C.; Kiy, Y.

2005-01-01

Full text: The effect of radioiodine ( 131 I) therapy in Graves' disease is gradual and the patients continue to be hyperthyroid for much time after this therapy. In a retrospective study, we compared the evolution of 196 patients in this situation treated with some therapeutic regimens. They received propylthiouracil or methimazole (ATD), one of them and potassium iodide (KI), KI only, or no drugs after 131 I therapy. ATD was started usually one day and KI two months after the radioiodine. The groups had similar age, pretreatment serum T 4 concentrations and 131 I treatment dose. Cure of the hyperthyroidism occurred in 83,9%, 75,5%, 75,0% and 70,6% in no-drugs, KI, ATD and KI-ATD groups, respectively. Hyperthyroidism was longer in KI and KI-ATD groups. Definitive hypothyroidism occurred in 39,2%, 47,2%, 52,9% and 66,1% in KI-ATD, KI, ATD and no-drugs groups, respectively. This condition appeared more quickly in no-drugs and ATD groups. Conclusion: We conclude that KI and ATD groups had similar evolutions as to cure of hyperthyroidism and occurrence of hypothyroidism. (author)

Impact of Active Drug Use on Antiretroviral Therapy Adherence and Viral Suppression in HIV-infected Drug Users

OpenAIRE

Arnsten, Julia H; Demas, Penelope A; Grant, Richard W; Gourevitch, Marc N; Farzadegan, Homayoon; Howard, Andrea A; Schoenbaum, Ellie E

2002-01-01

Despite a burgeoning literature on adherence to HIV therapies, few studies have examined the impact of ongoing drug use on adherence and viral suppression, and none of these have utilized electronic monitors to quantify adherence among drug users. We used 262 electronic monitors to measure adherence with all antiretrovirals in 85 HIV-infected current and former drug users, and found that active cocaine use, female gender, not receiving Social Security benefits, not being married, screening po...

Magnetic resonance imaging in relation to EEG epileptic foci in tuberous sclerosis

International Nuclear Information System (INIS)

Tamaki, Kyoko; Okuno, Takehiko; Ito, Masatoshi; Asato, Reinin; Konishi, Junji; Mikawa, Haruki

1990-01-01

In 20 patients with tuberous sclerosis (TS), who were sequentially treated for epilepsy at our clinic, the high signal lesions in the cerebral cortex and subcortex detected on T2 weighted magnetic resonance imaging (MRI) were compared with the interictal EEG findings. In four cases who showed a unilateral distribution of the MRI lesions, there was a good correlation between the laterality of the affected lobes and the localization of the EEG epileptic foci. Thirteen cases with more than four affected lobes in both hemispheres also showed bilateral epileptic foci on EEG. The MRI lesions in the occipital lobes showed the best correlation with the EEG epileptic foci, while the worst correlation was seen in the frontal lobes. In addition, the cases with four or more affected lobes without laterality on MRI are more likely to show bilateral synchronization on EEG. The prognosis of epilepsy in these cases was found to be rather poor. (author)

VNS Therapy versus the latest antiepileptic drug.

Science.gov (United States)

Ben-Menachem, Elinor; French, Jacqueline A

2005-09-01

Pro AED: The central issue in medical decision-making is risk-benefit assessment. Surgery of any type is still considered to be a major undertaking. To warrant these risks, the patient has a right to expect that they have a greater chance of a good outcome with an invasive therapy than with a non-invasive one. The main question is when, if ever, this becomes the case when comparing implantation of a VNS Therapy System versus adding an antiepileptic drug (AED)? After the first drug? The second? After all AEDs have failed? To date, no randomized trial comparing the addition of an AED against vagus nerve stimulation (VNS Therapy) has been undertaken, although several are currently being contemplated. Without this information, it is more difficult to make a case for early implementation of VNS Therapy. Unfortunately, few data are available regarding the potential for patients to become seizure-free after implantation of a VNS Therapy System. Another issue is side effects. It is important to remember that VNS Therapy also produces adverse events, albeit very different in character than those associated with AEDs, to which physicians have become accustomed. These include cough, dyspnea, pharyngitis, voice alteration and sleep apnea. A less frequently discussed, potentially negative consequence of VNS Therapy relates to the ability to obtain imaging of the patient. Patients who have undergone VNS Therapy System implantation are not candidates for imaging of the chest, breast, or abdomen. A second issue is that imaging of the brain can only be performed with MRI scanners that meet certain requirements, and as MRI technology develops, scanners meeting these requirements may become harder to find. However, to summarize, VNS Therapy is an excellent and useful treatment choice. Fortunately, the choice between AEDs and VNS Therapy is not an "either/or" decision. Each has a role in the treatment of patients with epilepsy, and the advantages and disadvantages of each should be

Synergistic gene and drug tumor therapy using a chimeric peptide.

Science.gov (United States)

Han, Kai; Chen, Si; Chen, Wei-Hai; Lei, Qi; Liu, Yun; Zhuo, Ren-Xi; Zhang, Xian-Zheng

2013-06-01

Co-delivery of gene and drug for synergistic therapy has provided a promising strategy to cure devastating diseases. Here, an amphiphilic chimeric peptide (Fmoc)2KH7-TAT with pH-responsibility for gene and drug delivery was designed and fabricated. As a drug carrier, the micelles self-assembled from the peptide exhibited a much faster doxorubicin (DOX) release rate at pH 5.0 than that at pH 7.4. As a non-viral gene vector, (Fmoc)(2)KH(7)-TAT peptide could satisfactorily mediate transfection of pGL-3 reporter plasmid with or without the existence of serum in both 293T and HeLa cell-lines. Besides, the endosome escape capability of peptide/DNA complexes was investigated by confocal laser scanning microscopy (CLSM). To evaluate the co-delivery efficiency and the synergistic anti-tumor effect of gene and drug, p53 plasmid and DOX were simultaneously loaded in the peptide micelles to form micelleplexes during the self-assembly of the peptide. Cellular uptake and intracellular delivery of gene and drug were studied by CLSM and flow cytometry respectively. And p53 protein expression was determined via Western blot analysis. The in vitro cytotoxicity and in vivo tumor inhibition effect were also studied. Results suggest that the co-delivery of gene and drug from peptide micelles resulted in effective cell growth inhibition in vitro and significant tumor growth restraining in vivo. The chimeric peptide-based gene and drug co-delivery system will find great potential for tumor therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

An epileptic seizures detection algorithm based on the empirical mode decomposition of EEG.

Science.gov (United States)

Orosco, Lorena; Laciar, Eric; Correa, Agustina Garces; Torres, Abel; Graffigna, Juan P

2009-01-01

Epilepsy is a neurological disorder that affects around 50 million people worldwide. The seizure detection is an important component in the diagnosis of epilepsy. In this study, the Empirical Mode Decomposition (EMD) method was proposed on the development of an automatic epileptic seizure detection algorithm. The algorithm first computes the Intrinsic Mode Functions (IMFs) of EEG records, then calculates the energy of each IMF and performs the detection based on an energy threshold and a minimum duration decision. The algorithm was tested in 9 invasive EEG records provided and validated by the Epilepsy Center of the University Hospital of Freiburg. In 90 segments analyzed (39 with epileptic seizures) the sensitivity and specificity obtained with the method were of 56.41% and 75.86% respectively. It could be concluded that EMD is a promissory method for epileptic seizure detection in EEG records.

Carbon nanotubes as a novel drug delivery system for anticancer therapy: a review

International Nuclear Information System (INIS)

Kushwaha, Swatantra Kumar Singh; Ghoshal, SauravI; Rai, Awani Kumar; Singh, Satyawan

2013-01-01

Carbon nanotubes (CNTs) were discovered in 1991 and shown to have certain unique physicochemical properties, attracting considerable interest in their application in various fields including drug delivery. The unique properties of CNTs such as ease of cellular uptake, high drug loading, thermal ablation, among others, render them useful for cancer therapy. Cancer is one of the most challenging diseases of modern times because its therapy involves distinguishing normal healthy cells from affected cells. Here, CNTs play a major role because phenomena such as EPR, allow CNTs to distinguish normal cells from affected ones, the Holy Grail in cancer therapy. Considerable work has been done on CNTs as drug delivery systems over the last two decades. However, concerns over certain issues such as biocompatibility and toxicity have been raised and warrant extensive research in this field. (author)

Carbon nanotubes as a novel drug delivery system for anticancer therapy: a review

Directory of Open Access Journals (Sweden)

Swatantra Kumar Singh Kushwaha

2013-12-01

Full Text Available Carbon nanotubes (CNTs were discovered in 1991 and shown to have certain unique physicochemical properties, attracting considerable interest in their application in various fields including drug delivery. The unique properties of CNTs such as ease of cellular uptake, high drug loading, thermal ablation, among others, render them useful for cancer therapy. Cancer is one of the most challenging diseases of modern times because its therapy involves distinguishing normal healthy cells from affected cells. Here, CNTs play a major role because phenomena such as EPR, allow CNTs to distinguish normal cells from affected ones, the Holy Grail in cancer therapy. Considerable work has been done on CNTs as drug delivery systems over the last two decades. However, concerns over certain issues such as biocompatibility and toxicity have been raised and warrant extensive research in this field.

Carbon nanotubes as a novel drug delivery system for anticancer therapy: a review

Energy Technology Data Exchange (ETDEWEB)

Kushwaha, Swatantra Kumar Singh; Ghoshal, SauravI; Rai, Awani Kumar, E-mail: swatantrakushwaha@yahoo.co.in [Pranveer Singh Institute of Technology, Kanpur (India); Singh, Satyawan [Saroj Institute of Technology and Management, Lucknow (India)

2013-10-15

Carbon nanotubes (CNTs) were discovered in 1991 and shown to have certain unique physicochemical properties, attracting considerable interest in their application in various fields including drug delivery. The unique properties of CNTs such as ease of cellular uptake, high drug loading, thermal ablation, among others, render them useful for cancer therapy. Cancer is one of the most challenging diseases of modern times because its therapy involves distinguishing normal healthy cells from affected cells. Here, CNTs play a major role because phenomena such as EPR, allow CNTs to distinguish normal cells from affected ones, the Holy Grail in cancer therapy. Considerable work has been done on CNTs as drug delivery systems over the last two decades. However, concerns over certain issues such as biocompatibility and toxicity have been raised and warrant extensive research in this field. (author)

Idiopathic epileptic syndromes and cognition.

Science.gov (United States)

Hommet, Caroline; Sauerwein, Hannelore C; De Toffol, Bertrand; Lassonde, Maryse

2006-01-01

Epilepsy is frequently associated with cognitive impairments which result from various interacting factors. The present paper deals with the contribution of neuropsychology to the characterization of the type of epilepsy and the possible mechanisms underlying idiopathic epileptic syndromes. The non-lesional, so-called idiopathic epilepsies, constitute an interesting model for assessing the relationship between epileptiform EEG discharges and cognition. Among the idiopathic generalized epilepsies, disorders of social integration and personality have been frequently reported in juvenile myoclonic epilepsy (JME). Since similar disturbances are observed in frontal-lobe-lesioned patients, impairments in other frontal lobe functions (e.g. executive functions) might be expected in JME. This gives rise to speculation about the possible underlying pathophysiological mechanisms in JME. With regard to partial idiopathic epilepsies, benign childhood epilepsy with centrotemporal spikes (BCECTS) may provide a useful model for the study of the relationship between epileptiform EEG discharges in the peri-sylvian region and language functions. Furthermore, the description of mild cognitive dysfunctions in BCECTS, and their persistence into adulthood, can provide information about compensatory mechanisms and may allow for the generation of remedial strategies. Thus, 'lesional' neuropsychology has given way to 'dynamic' neuropsychology based on specific postulates. By using the cognitive profile to specify the mechanism underlying the behavioral disturbances observed in different types of epilepsy, neuropsychology may eventually contribute to a revision of the present classification of epileptic syndromes. In addition, the neuropsychological data may help predict the extent and limits of functional recovery and cerebral plasticity.

Childhood masturbation simulating epileptic seizures: A report of ...

African Journals Online (AJOL)

owner

2013-03-01

Mar 1, 2013 ... Childhood masturbation is re- garded as one of the paroxysmal, non-epileptic disorders in children, which incorporate several potential diagno- ses. Therefore, if not recognized, it could pose diagnos- tic difficulties, unnecessary investigative spending and considerable parental anxiety.3. There is paucity of ...

Drug taper during long-term video-EEG monitoring

DEFF Research Database (Denmark)

Guld, A. T.; Sabers, A.; Kjaer, T. W.

2017-01-01

Objectives: Anti-epileptic drugs (AED) are often tapered to reduce the time needed to record a sufficient number of seizure during long-term video-EEG monitoring (LTM). Fast AED reduction is considered less safe, but few studies have examined this. Our goal is to examine whether the rate of AED r...

Ursodeoxycholic Acid Can Improve Liver Transaminase Quantities in Children with Anticonvulsant Drugs Hepatotoxicity: a Pilot Study.

Directory of Open Access Journals (Sweden)

Masoumeh Asgarshirazi

2015-06-01

Full Text Available The present study has been directed to investigate Ursodeoxycholic Acid (UDCA effect in children, to reduce the high Liver transaminases induced by Anticonvulsant drugs (drug induced hepatitis. This idea has been driven from Cytoprotective and antioxidant properties of UDCA to be used in drug induced inflammation in Liver. Twenty two epileptic patients aged between 4 mo - 3 yr whom were under anticonvulsant therapy with drugs such as valperoic acid, primidone, levetiracetam, Phenobarbital or any combination of them and had shown Liver transaminases rise , after rule out of Viral-Autoimmune, Metabolic and Anatomic causes, have been prescribed UDCA in dose of 10-15 mg/kg/day, at least for 6 months. Any patient who have shown confusing factors such as genetic disorders with liver involvement or spontaneous decline in enzymes or had not treatment compliance has been excluded from the study. Transaminases range changes as well as Probable side effects of the drug have been monitored. The results indicated that UDCA is effective and well tolerable in the children with drug induced hyper transaminasemia. No side effect has been seen and recorded in this study. Based on this study and its results, we recommend UDCA as a safe and effective choice in drug induced hepatotoxicities.

Localisation of epileptic foci using novel imaging modalities

Science.gov (United States)

De Ciantis, Alessio; Lemieux, Louis

2013-01-01

Purpose of review This review examines recent reports on the use of advanced techniques to map the regions and networks involved during focal epileptic seizure generation in humans. Recent findings A number of imaging techniques are capable of providing new localizing information on the ictal processes and epileptogenic zone. Evaluating the clinical utility of these findings has been mainly performed through post-hoc comparison with the findings of invasive EEG and ictal single-photon emission computed tomography, using postsurgical seizure reduction as the main outcome measure. Added value has been demonstrated in MRI-negative cases. Improved understanding of the human ictiogenic processes and the focus vs. network hypothesis is likely to result from the application of multimodal techniques that combine electrophysiological, semiological, and whole-brain coverage of brain activity changes. Summary On the basis of recent research in the field of neuroimaging, several novel imaging modalities have been improved and developed to provide information about the localization of epileptic foci. PMID:23823464

Two drugs are better than one. A short history of combined therapy of ovarian cancer.

Science.gov (United States)

Bukowska, Barbara; Gajek, Arkadiusz; Marczak, Agnieszka

2015-01-01

Combined therapy of ovarian cancer has a long history. It has been applied for many years. The first drug which was commonly combined with other chemotherapeutics was cisplatin. It turned out to be effective given together with alkylating agents as well as with taxanes. Another drug which is often the basis of first-line therapy is doxorubicin. The use of traditional chemotherapy is often limited due to side effects. This is why new drugs, targeted specifically at cancer cells (e.g. monoclonal antibodies or epidermal growth factor receptor inhibitors), offer a welcome addition when used in combination with conventional anticancer agents. Drugs applied in combination should be synergistic or at least additive. To evaluate the type of interaction between drugs in a plausible sequence, isobolographic analysis is used. This method allows one to assess whether the two agents could make an efficient combination, which might improve the therapy of ovarian cancer.

Limits of 2D-TCA in detecting BOLD responses to epileptic activity.

Science.gov (United States)

Khatamian, Yasha Borna; Fahoum, Firas; Gotman, Jean

2011-05-01

Two-dimensional temporal clustering analysis (2D-TCA) is a relatively new functional MRI (fMRI) based technique that breaks blood oxygen level dependent activity into separate components based on timing and has shown potential for localizing epileptic activity independently of electroencephalography (EEG). 2D-TCA has only been applied to detect epileptic activity in a few studies and its limits in detecting activity of various forms (i.e. activation size, amplitude, and frequency) have not been investigated. This study evaluated 2D-TCA's ability to detect various forms of both simulated epileptic activity and EEG-fMRI activity detected in patients. When applied to simulated data, 2D-TCA consistently detected activity in 6min runs containing 5 spikes/run, 10 spikes/run, and one 5s long event with hemodynamic response function amplitudes of at least 1.5%, 1.25%, and 1% above baseline respectively. When applied to patient data, while detection of interictal spikes was inconsistent, 2D-TCA consistently produced results similar to those obtained by EEG-fMRI when at least 2 prolonged interictal events (a few seconds each) occurred during the run. However, even for such cases it was determined that 2D-TCA can only be used to validate localization by other means or to create hypotheses as to where activity may occur, as it also detects changes not caused by epileptic activity. Copyright © 2011 Elsevier B.V. All rights reserved.

The ketogenic diet is effective for refractory epilepsy associated with acquired structural epileptic encephalopathy.

Science.gov (United States)

Villaluz, Mel Michel; Lomax, Lysa Boissé; Jadhav, Trupti; Cross, J Helen; Scheffer, Ingrid E

2018-07-01

Ketogenic diet therapies have proven efficacy for refractory epilepsy. There are many reports of their use in the genetic developmental and epileptic encephalopathies; however, little attention has been paid as to whether the diet is also effective in individuals with an acquired structural aetiology. We observed remarkable efficacy of the diet in two patients with hypoxic-ischaemic encephalopathy. We then analysed our cases with refractory structural epilepsies of acquired origin to characterize their response to the ketogenic diet. The classical ketogenic diet was implemented with dietary ratios of 3:1 to 4.4:1. Seizure frequency at 1 month, 3 months, 6 months, 1 year, and 2 years was ascertained. A responder was defined as greater than 50% seizure reduction compared to baseline. Seven of the nine patients were responders at 3 months. Somewhat surprisingly we found that the ketogenic diet was effective in patients with a developmental and epileptic encephalopathy due to an acquired structural aetiology. This cohort may not be routinely considered for the ketogenic diet because of their structural and acquired, rather than genetic, basis. The ketogenic diet should be considered early in the management of patients with acquired structural encephalopathies as it can improve seizure control with the potential to improve developmental outcome. The ketogenic diet was effective in children with epilepsy associated with an acquired structural aetiology. © 2018 Mac Keith Press.

Emperor Napoleon Bonaparte: did he have seizures? Psychogenic or epileptic or both?

Science.gov (United States)

Hughes, John R

2003-12-01

Napoleon Bonaparte was a general in the French army at 24 years of age, later conquering most of Europe. He was one of the greatest military geniuses the world has ever known, but also an extremely intelligent individual. Did he have seizures? The evidence shows that he had both psychogenic and epileptic attacks. The psychogenic attacks were likely related to the tremendous stress in his life, and the epileptic seizures were the result of chronic uremia from a severe urethral stricture caused by gonorrhea that was transmitted from his wife, Empress Josephine.

Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy.

Science.gov (United States)

Piktel, Ewelina; Niemirowicz, Katarzyna; Wątek, Marzena; Wollny, Tomasz; Deptuła, Piotr; Bucki, Robert

2016-05-26

The rapid development of nanotechnology provides alternative approaches to overcome several limitations of conventional anti-cancer therapy. Drug targeting using functionalized nanoparticles to advance their transport to the dedicated site, became a new standard in novel anti-cancer methods. In effect, the employment of nanoparticles during design of antineoplastic drugs helps to improve pharmacokinetic properties, with subsequent development of high specific, non-toxic and biocompatible anti-cancer agents. However, the physicochemical and biological diversity of nanomaterials and a broad spectrum of unique features influencing their biological action requires continuous research to assess their activity. Among numerous nanosystems designed to eradicate cancer cells, only a limited number of them entered the clinical trials. It is anticipated that progress in development of nanotechnology-based anti-cancer materials will provide modern, individualized anti-cancer therapies assuring decrease in morbidity and mortality from cancer diseases. In this review we discussed the implication of nanomaterials in design of new drugs for effective antineoplastic therapy and describe a variety of mechanisms and challenges for selective tumor targeting. We emphasized the recent advantages in the field of nanotechnology-based strategies to fight cancer and discussed their part in effective anti-cancer therapy and successful drug delivery.

Using bivariate signal analysis to characterize the epileptic focus: the benefit of surrogates.

Science.gov (United States)

Andrzejak, R G; Chicharro, D; Lehnertz, K; Mormann, F

2011-04-01

The disease epilepsy is related to hypersynchronous activity of networks of neurons. While acute epileptic seizures are the most extreme manifestation of this hypersynchronous activity, an elevated level of interdependence of neuronal dynamics is thought to persist also during the seizure-free interval. In multichannel recordings from brain areas involved in the epileptic process, this interdependence can be reflected in an increased linear cross correlation but also in signal properties of higher order. Bivariate time series analysis comprises a variety of approaches, each with different degrees of sensitivity and specificity for interdependencies reflected in lower- or higher-order properties of pairs of simultaneously recorded signals. Here we investigate which approach is best suited to detect putatively elevated interdependence levels in signals recorded from brain areas involved in the epileptic process. For this purpose, we use the linear cross correlation that is sensitive to lower-order signatures of interdependence, a nonlinear interdependence measure that integrates both lower- and higher-order properties, and a surrogate-corrected nonlinear interdependence measure that aims to specifically characterize higher-order properties. We analyze intracranial electroencephalographic recordings of the seizure-free interval from 29 patients with an epileptic focus located in the medial temporal lobe. Our results show that all three approaches detect higher levels of interdependence for signals recorded from the brain hemisphere containing the epileptic focus as compared to signals recorded from the opposite hemisphere. For the linear cross correlation, however, these differences are not significant. For the nonlinear interdependence measure, results are significant but only of moderate accuracy with regard to the discriminative power for the focal and nonfocal hemispheres. The highest significance and accuracy is obtained for the surrogate-corrected nonlinear

Antibody-drug conjugates for cancer therapy: The technological and regulatory challenges of developing drug-biologic hybrids.

Science.gov (United States)

Hamilton, Gregory S

2015-09-01

Antibody-drug conjugates (ADCs) are a new class of therapeutic agents that combine the targeting ability of monoclonal antibodies (mAbs) with small molecule drugs. The combination of a mAb targeting a cancer-specific antigen with a cytotoxin has tremendous promise as a new type of targeted cancer therapy. Two ADCs have been approved and many more are in clinical development, suggesting that this new class of drugs is coming to the forefront. Because of their unique nature as biologic-small drug hybrids, ADCs are challenging to develop, from both the scientific and regulatory perspectives. This review discusses both these aspects in current practice, and surveys the current state of the art of ADC drug development. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Dynamic imaging of coherent sources reveals different network connectivity underlying the generation and perpetuation of epileptic seizures.

Directory of Open Access Journals (Sweden)

Lydia Elshoff

Full Text Available The concept of focal epilepsies includes a seizure origin in brain regions with hyper synchronous activity (epileptogenic zone and seizure onset zone and a complex epileptic network of different brain areas involved in the generation, propagation, and modulation of seizures. The purpose of this work was to study functional and effective connectivity between regions involved in networks of epileptic seizures. The beginning and middle part of focal seizures from ictal surface EEG data were analyzed using dynamic imaging of coherent sources (DICS, an inverse solution in the frequency domain which describes neuronal networks and coherences of oscillatory brain activities. The information flow (effective connectivity between coherent sources was investigated using the renormalized partial directed coherence (RPDC method. In 8/11 patients, the first and second source of epileptic activity as found by DICS were concordant with the operative resection site; these patients became seizure free after epilepsy surgery. In the remaining 3 patients, the results of DICS / RPDC calculations and the resection site were discordant; these patients had a poorer post-operative outcome. The first sources as found by DICS were located predominantly in cortical structures; subsequent sources included some subcortical structures: thalamus, Nucl. Subthalamicus and cerebellum. DICS seems to be a powerful tool to define the seizure onset zone and the epileptic networks involved. Seizure generation seems to be related to the propagation of epileptic activity from the primary source in the seizure onset zone, and maintenance of seizures is attributed to the perpetuation of epileptic activity between nodes in the epileptic network. Despite of these promising results, this proof of principle study needs further confirmation prior to the use of the described methods in the clinical praxis.

Access to antiepileptic drug therapy in children in Camagüey Province, Cuba

Science.gov (United States)

Arencibia, Zeina Bárzaga; Leyva, Alberto López; Peña, Yordanka Mejías; Reyes, Alba Rosa González; Nápolez, Maurilys Acosta; Carbonell Perdomo, Demetrio; Manzano, Edita Fernández; Choonara, Imti

2012-01-01

Objective To describe access to antiepileptic drug therapy and estimate the prevalence of epilepsy in children in Camagüey Province, Cuba. Methods All the community pharmacies in the province were visited and information collected about the number of children receiving antiepileptic drugs in 2009. Availability and cost of each antiepileptic drug were determined. The prevalence of epilepsy was estimated by determining the number of children receiving antiepileptic drugs. Results There were 923 children who received a total of 977 antiepileptic drugs in Camagüey Province. The estimated prevalence of epilepsy was 5.18 per thousand children which is lower than previously reported rates in other low and lower-middle income countries. Most of the children (871, 94%) received a single antiepileptic drug. Carbamazepine and valproate were the two most frequently prescribed antiepileptic drugs. Antiepileptic drugs were available from the local pharmacy on 76% of occasions. If the antiepileptic drug was not available from the local pharmacy, the parent had to travel to another pharmacy to obtain the medicine. Conclusions The estimated prevalence of epilepsy in children in Cuba is lower than that estimated in other lower-middle income countries. Access to drug therapy in children with epilepsy can be achieved in lower-middle income countries. PMID:23134098

Salvage Therapy of Multiple Myeloma: The New Generation Drugs

Directory of Open Access Journals (Sweden)

Alessandra Romano

2014-01-01

Full Text Available During the past decade, overall results of treatment of multiple myeloma (MM have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs. However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and therapeutic strategies are required for continued disease control. In this review, we summarize new insights in salvage therapy for relapsed/refractory MM as emerging from recent clinical trials exploring the activity of bendamustine, new generation proteasome inhibitors, novel IMiDs, monoclonal antibodies, and drugs interfering with growth pathways.

Salvage Therapy of Multiple Myeloma: The New Generation Drugs

Science.gov (United States)

Romano, Alessandra; Conticello, Concetta; Di Raimondo, Cosimo; Schinocca, Elena; La Fauci, Alessia; Parrinello, Nunziatina Laura; Chiarenza, Annalisa

2014-01-01

During the past decade, overall results of treatment of multiple myeloma (MM) have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs). However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and therapeutic strategies are required for continued disease control. In this review, we summarize new insights in salvage therapy for relapsed/refractory MM as emerging from recent clinical trials exploring the activity of bendamustine, new generation proteasome inhibitors, novel IMiDs, monoclonal antibodies, and drugs interfering with growth pathways. PMID:24967371

Nanotechnology-based combinational drug delivery: an emerging approach for cancer therapy.

Science.gov (United States)

Parhi, Priyambada; Mohanty, Chandana; Sahoo, Sanjeeb Kumar

2012-09-01

Combination therapy for the treatment of cancer is becoming more popular because it generates synergistic anticancer effects, reduces individual drug-related toxicity and suppresses multi-drug resistance through different mechanisms of action. In recent years, nanotechnology-based combination drug delivery to tumor tissues has emerged as an effective strategy by overcoming many biological, biophysical and biomedical barriers that the body stages against successful delivery of anticancer drugs. The sustained, controlled and targeted delivery of chemotherapeutic drugs in a combination approach enhanced therapeutic anticancer effects with reduced drug-associated side effects. In this article, we have reviewed the scope of various nanotechnology-based combination drug delivery approaches and also summarized the current perspective and challenges facing the successful treatment of cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.

Individualization of anticancer therapy; molecular targets of novel drugs in oncology

Directory of Open Access Journals (Sweden)

Katarzyna Regulska

2012-11-01

Full Text Available Deregulation of cellular signal transduction, caused by gene mutations, has been recognized as a basic factor of cancer initiation, promotion and progression. Thus, the ability to control the activity of overstimulated signal molecules by the use of appropriate inhibitors became the idea of targeted cancer therapy, which has provided an effective tool to normalize the molecular disorders in malignant cells and to treat certain types of cancer. The molecularly targeted drugs are divided into two major pharmaceutical classes: monoclonal antibodies and small-molecule kinase inhibitors. This review presents a summary of their characteristics, analyzing their chemical structures, specified molecular targets, mechanisms of action and indications for use. Also the molecules subjected to preclinical trials or phase I, II and III clinical trials evaluating their efficiency and safety are presented. Moreover, the article discusses further perspectives for development of targeted therapies focusing on three major directions: systematic searching and discovery of new targets that are oncogenic drivers, improving the pharmacological properties of currently known drugs, and developing strategies to overcome drug resistance. Finally, the role of proper pharmacodiagnostics as a key to rational anticancer therapy has been emphasized since the verification of reliable predictive biomarkers is a basis of individualized medicine in oncology. 

[Modern aspects of epilepsy treatment].

Science.gov (United States)

Alajbegović, Azra; Kantardzić, Dzelaludin; Suljić, Enra; Alajbegović, Salem

2003-01-01

It is a general rule today, after a relevant diagnostics of an epilepsy, to start a monotherapy treatment, depending on a kind of a seizure, a life age and a general health condition. First line of monotherapy epilepsy drugs remain carbamazapine and sodium valproat. New drugs that are being introduced are: felbamat, gabapentin, lamotrigin, oxcarbazepin, tiagabin, topiramat, vigabatin and zanisamid. These are commonly used as add-on therapy, or as an addition for previously used antiepileptic. Their indicated areas are complex resistant partial seizures with or without generalization. Attention should be paid on proper dosage, interactions and toxicity. Regardless on the new epileptic era, according to reports of International League against epilepsy, most of the patients do not receive the drug that is the most appropriate for them concerning the price (cost-benefit). Neurosurgical methods in epilepsy treatment are: selective amygdalo-hyppocampotomy, temporal lobotomy, subpial resection, hemispherectomy, corpus callosotomy, removal of lesions like tumors or cysts provide encouraging results in reduction of epileptic seizures that can be followed by reduction of drug therapy. N. vagus stimulation is being wider introduced in resident epileptics. Treatment of epilepsy in women requires an approach to sexuality, conception, pregnancy, introduction of medicaments, antiepileptic terratogenity, contraception, motherhood and menopause. A special significance of modern approach to epilepsy is in treatment of elderly who have cerebrovascular and neurodegenerative disease as a cause of seizures. A complex treatment of epilepsy using pharmacological and neurosurgical approach requires supportive psychotherapy, socio-therapy, the work with a family, education about epilepsy and living a life with more quality having one.

CT findings in epileptic children

International Nuclear Information System (INIS)

Koide, Nobuo; Kimura, Shigeru; Watanabe, Jun; Haneda, Satoshi; Takebe, Yukinao

1981-01-01

CT findings in 43 children with generalized seizures (grand mal seizures) (GM group) and in 50 children with partial seizures (P group), classified according to clinical seizure type, were studied. 1) CT abnormalities were demonstrated in 19% (8/43) in GM group and in 40% (20/50) in P group, including localized CT abnormalities in 9.3% (4/43) and in 34% (17/50) respectively. CT abnormalities were found more frequently in cases with abnormal past histories and/or mental defects (MD) than in those without them. 2) In P group, localized CT abnormalities and generalized brain atrophy were observed in 13 and 7 cases respectively. In 40 cases with focal epileptic discharges (FED) in EEG, localized CT abnormalities were demonstrated in 23% (9/40). The sites of localized CT abnormalities corresponded in 73% (11/15) to the sites of focal suppression in EEG (i.e., slowing, low amplitude and lazy pattern) regardless of FED. 3) The bicaudate cerebro-ventricular index (B-CVI) in 19 cases in the normal control group over 2 years of age was 10.0 +- 1.2 (mean +- SD). Ventricular narrowing (VN), with B-CVI less than 8.2 (mean - 1.5 SD), was observed in 5, 17 and 27% in control, GM and P groups respectively, indicating more frequently in epileptic children than in normal controls. Seizures were well controlled in 85% (11/13) in VN group and in 70% (26/36) in normal ventricular group. Brain atrophy in CT findings to inspection was ascertained in all cases by measuring B-CVI. (author)

Multifractal detrended cross-correlation analysis for epileptic patient in seizure and seizure free status

International Nuclear Information System (INIS)

Ghosh, Dipak; Dutta, Srimonti; Chakraborty, Sayantan

2014-01-01

Highlights: • We analyze EEG of patients during seizure and in seizure free interval. • Data from different sections of the brain and seizure activity was analyzed. • Assessment of cross-correlation in seizure and seizure free interval using MF-DXA technique. - Abstract: This paper reports a study of EEG data of epileptic patients in terms of multifractal detrended cross-correlation analysis (MF-DXA). The EEG clinical data were obtained from the EEG Database available with the Clinic of Epileptology of the University Hospital of Bonn, Germany. The data sets (C, D, and E) were taken from five epileptic patients undergoing presurgical evaluations. The data sets consist of intracranial EEG recordings during seizure-free intervals (interictal periods) from within the epileptogenic zone (D) and from the hippocampal formation of the opposite hemisphere of the epileptic patients’ brain, respectively (C). The data set (E) was recorded during seizure activity (ictal periods). MF-DXA is a very rigorous and robust tool for assessment of cross-correlation among two nonlinear time series. The study reveals the degree of cross-correlation is more among seizure and seizure free interval in epileptogenic zone. These data are very significant for diagnosis, onset and prognosis of epileptic patients

Recognition of psychogenic non-epileptic seizures: a curable neurophobia?

LENUS (Irish Health Repository)

O'Sullivan, S S

2013-02-01

Diagnosing psychogenic non-epileptic seizures (PNES) remains challenging. The majority of \\'PNES status\\' cases are likely to be seen in the emergency department or similar non-specialised units, where patients are initially assessed and managed by physicians of varying expertise in neurology.

Toxins and derivatives in molecular pharmaceutics: Drug delivery and targeted therapy.

Science.gov (United States)

Zhan, Changyou; Li, Chong; Wei, Xiaoli; Lu, Wuyuan; Lu, Weiyue

2015-08-01

Protein and peptide toxins offer an invaluable source for the development of actively targeted drug delivery systems. They avidly bind to a variety of cognate receptors, some of which are expressed or even up-regulated in diseased tissues and biological barriers. Protein and peptide toxins or their derivatives can act as ligands to facilitate tissue- or organ-specific accumulation of therapeutics. Some toxins have evolved from a relatively small number of structural frameworks that are particularly suitable for addressing the crucial issues of potency and stability, making them an instrumental source of leads and templates for targeted therapy. The focus of this review is on protein and peptide toxins for the development of targeted drug delivery systems and molecular therapies. We summarize disease- and biological barrier-related toxin receptors, as well as targeted drug delivery strategies inspired by those receptors. The design of new therapeutics based on protein and peptide toxins is also discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

[Epilepsy from a metaphysical perspective: an interpretation of the biblical story of the epileptic boy and Raphael's Transfiguration].

Science.gov (United States)

Janz, D

1994-01-01

Raphael's last painting reveals, in the upper half of the picture, Christ's transfiguration on Mount Tabor and, in the lower half, the young boy's epileptic seizure at the foot of the mountain in the presence of the other disciples. Raphael depicts both events, which are told in succession in the Gospels, as if they took place at the same time. By synchronizing both scenes, Raphael demonstrated a significant correspondence between Christ and the epileptic boy which reveals the epileptic seizure as a symbolic representation of a transcendental event. This metaphysical aspect of epilepsy depicted by Raphael can also be found in the corresponding biblical passages. In the Gospels, the metamorphosis caused by the epileptic seizure is used as a simile for Christ's transfiguration through suffering, death and resurrection.

REHABILITATION THERAPY VERSUS DRUG THERAPY IN PATIENTS WITH LUMBAR DISC DEGENERATION

Directory of Open Access Journals (Sweden)

BROSCATEAN, Emanuela-Flavia

2013-12-01

Full Text Available Lumbar disc degeneration is a disorder whose clinical manifestations are represented by episodic pain in the lumbar spine, without lumbar blockage and minor muscle contraction. Because lumbalgia caused by lumbar disc degeneration is not always very high intensity pain, the easiest to apply treatment is drug therapy. The aim of this study was to analyze the potential role of rehabilitation treatment in the recovery of patients and the prevention of complications compared to drug therapy alone. The study included 28 patients (17 women and 11 men aged between 23-60 years, assigned to two groups: 20 patients who received rehabilitation treatment (consisting of massage, kinesiotherapy, hydrokinesiotherapy, electrotherapy and medication and 8 patients who received drug treatment consisting of anti-inflammatory and analgesic drugs. The treatment duration was 10 days. For the evaluation of pain, the visual analogue scale was used, for the degree of disability, the Oswestry questionnaire, and for joint mobility and muscle strength, articular and muscular testing. At the end of treatment, the study group compared to the control group had a statistically significant result for pain (p=0.001, as well as for the Oswestry score (p=0.030. The mean age of the patients was 35.51±3.026, which shows an increased incidence among young adults. A possible connection between the development of the disease in women and age less than 45 years was also investigated, but the result was not statistically significant, p=0.22. Our data suggest the fact that rehabilitation treatment plays an important role in the reduction of pain and the improvement of the quality of life of patients with lumbar disc degeneration by decreasing the degree of disability. In the future, it can be proposed to monitor patients with lumbar disc degeneration over a longer time period in order to see the effects of kinetic rehabilitation programs in relation to the delay of chronicization. As

Pharmokinetics in Drug Therapy as a Required Undergraduate Course

Science.gov (United States)

Schumacher, G. E.

1976-01-01

This course is offered in the third quarter of the fourth year of the five-year curriculum in pharmacology. The year includes (1) a 350-hour clinical clerkship, (2) two courses in "Case Studies in Drug Therapy," (3) one course in "Case Studies in Pharmacy Practice," and (4) professional electives. (LBH)

Use of peri-operative anti-epileptic drugs in patients with newly diagnosed high grade malignant glioma: a single center experience.

Science.gov (United States)

Lwu, Shelly; Hamilton, Mark G; Forsyth, Peter A; Cairncross, J Gregory; Parney, Ian F

2010-02-01

An American Academy of Neurology practice parameter recommends that long-term prophylactic anti-epileptic drugs (AED) should not be routine in patients with newly diagnosed brain tumors. However, prospective multi-center North American data shows that most newly diagnosed glioma patients receive prophylactic AED. We examined our own peri-operative AED practice patterns in newly-diagnosed patients with malignant glioma to determine if we deviate from published guidelines. A retrospective chart review was performed in adult patients with newly diagnosed malignant gliomas undergoing surgery in southern Alberta between January 2003 and December 2005. Demographic information, AED use, seizure incidence, adverse effects, tumor size, and tumor location were recorded. Of 164 eligible patients, 54 (33%) presented with seizures and all received AED. Prophylactic AED were given to 44 patients (27%). Peri-operative seizures (within 1 week) occurred in two patients without (3%) and no patients with seizure prophylaxis. Adverse AED reactions and adverse effects attributable to seizures were both rare. Prophylactic AED were continued >1 week post-op in 30 patients (18%). Patients receiving prophylactic AED were more likely to have had tumors involving the temporal lobe than those who did not (50 vs. 20%; P < 0.01). Patients receiving peri-operative AED prophylaxis were common, had a trend to reduced peri-operative seizures, and had few adverse effects. However, most of these patients were maintained on prophylactic AED continued beyond the first peri-operative week, contradicting published guidelines. Increased awareness of practice guidelines may help modify AED prescription patterns in malignant glioma patients.

Effects of Multidimensional Family Therapy (MDFT) on Nonopioid Drug Abuse:

DEFF Research Database (Denmark)

Filges, Trine; Andersen, Ditte; Jørgensen, Anne-Marie Klint

2015-01-01

trials. Meta-analytic methods were used to quantitatively synthesize study results.  Results: The search yielded five studies that met inclusion criteria. MDFT was found to be more effective than other treatments on drug abuse problem severity and drug use frequency in the short run but not in the long...... run and demonstrated positive effects on treatment retention compared to control conditions.  Discussion: While additional research is needed, the review offers support for MDFT as a treatment to young nonopioid drug abusers. The number of studies included in this review was limited, however......Purpose: This review evaluates the evidence of the effects of multidimensional family therapy (MDFT) on drug use reduction in young people for the treatment of nonopioid drug use.  Method: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized...

Complete remission of epileptic psychosis after temporal lobectomy: case report

Directory of Open Access Journals (Sweden)

Marchetti Renato Luiz

2001-01-01

Full Text Available We report a case of a female patient with refractory complex partial seizures since 15 years of age, recurrent postictal psychotic episodes since 35 which evolved to a chronic refractory interictal psychosis and MRI with right mesial temporal sclerosis (MTS. After a comprehensive investigation (video-EEG intensive monitoring, interictal and ictal SPECT, and a neuropsychological evaluation including WADA test she was submitted to a right temporal lobectomy. Since then, she has been seizure-free with remission of psychosis, although with some persistence of personality traits (hiperreligiosity, viscosity which had been present before surgery. This case supports the idea that temporal lobectomy can be a safe and effective therapeutic measure for patients with MTS, refractory epilepsy and recurrent postictal epileptic psychosis or interictal epileptic psychosis with postictal exacerbation.

First Analysis of the Association Between CYP3A4/5, ABCB1 Genetic Polymorphisms and Oxcarbazepine Metabolism and Transport in Chinese Epileptic Patients with Oxcarbazepine Monotherapy and Bitherapy.

Science.gov (United States)

Wang, Ping; Yin, Tao; Ma, Hong-ying; Liu, Dan-Qi; Sheng, Yangh-ao; Zhou, Bo-Ting

2015-01-01

Oxcarbazepine (OXC) is widely used in anti-epileptic treatment. Cytochrome P450 3A4 (CYP3A4), cytochrome P450 3A5(CYP3A5), and ATP-binding cassette sub-family B member 1 (ABCB1) are potential genes involved in OXC metabolisms and transport in vivo. This study aims to examine the genetic effects of CYP3A4, CYP3A5, and ABCB1 on OXC metabolism and transport in Chinese epileptic patients using OXC as monotherapy and bitherapy with lamotrigine (LTG), levetiracetam (LEV), or valproic acid (VPA). Sixty-six Chinese epileptic patients were recruited from Xiangya Hospital Central South University, of whom 40 patients were receiving OXC monotherapy, 11 patients were placed in the OXC bitherapy group combined with one enzyme-inducing anti-epileptic drugs (LTG or LEV), and 15 patients were placed in the OXC bitherapy group combined with VPA. Oxcarbazepine and its main metabolite 10-hydrocarbazepine (MHD) plasma concentrations were measured using high performance liquid chromatography (HPLC)-UV method. In addition, eight single nucleotide polymorphisms (SNPs) in CYP3A4, CYP3A5, ABCB1 gene were genotyped by polymerase chain reaction-improved multiple ligase detection reaction (PCR-iMLDR). In the OXC+VPA group, ABCB1 rs2032582 and rs2032582-rs10234411-rs1045642 TAG haplotype were associated with MHD and MHD+OXC plasma concentration before permutation test. In OXC monotherapy and OXC+ LTG/LEV groups, no significant association between genetic polymorphisms in CYP3A4/5, ABCB1 gene and OXC plasma concentration parameters were observed. CYP3A4/5 and ABCB1 genetic variants might not take part in the metabolism and transport of MHD and OXC among epileptic patients using OXC monotherapy and bitherapy in combination with LEV, LTG or VPA.

The epileptic seizure and the mystery of death in Christian painting.

Science.gov (United States)

Mann, Michael W

2010-02-01

The epileptic seizure is in many cultures associated with death. Indo-European tradition perceives death not necessarily as the end but as a step, as a point the life cycle is passing through. The epileptic seizure may be seen as a transient form of death, which offers some symmetry with the biblical story of the death and resurrection of Christ. This article, originating from a case report, shows how some Christian painting alludes to renaissance after a seizure and to the parallelism between the patient with epilepsy and the destiny of Christ. Special attention is paid to Raphael's, in this respect particularly complex work, The Transfiguration. (c) 2009 Elsevier Inc. All rights reserved.

Affordable HIV drug-resistance testing for monitoring of antiretroviral therapy in sub-Saharan Africa.

Science.gov (United States)

Inzaule, Seth C; Ondoa, Pascale; Peter, Trevor; Mugyenyi, Peter N; Stevens, Wendy S; de Wit, Tobias F Rinke; Hamers, Raph L

2016-11-01

Increased provision of antiretroviral therapy in sub-Saharan Africa has led to a growing number of patients with therapy failure and acquired drug-resistant HIV, driving the demand for more costly further lines of antiretroviral therapy. In conjunction with accelerated access to viral load monitoring, feasible and affordable technologies to detect drug-resistant HIV could help maximise the durability and rational use of available drug regimens. Potential low-cost technologies include in-house Sanger and next-generation sequencing in centralised laboratories, and point mutation assays and genotype-free systems that predict response to antiretroviral therapy at point-of-care. Strengthening of centralised high-throughput laboratories, including efficient systems for sample referral and results delivery, will increase economies-of-scale while reducing costs. Access barriers can be mitigated by standardisation of in-house assays into commercial kits, use of polyvalent instruments, and adopting price-reducing strategies. A stepwise rollout approach should improve feasibility, prioritising WHO-recommended population-based surveillance and management of complex patient categories, such as patients failing protease inhibitor-based antiretroviral therapy. Implementation research, adaptations of existing WHO guidance, and political commitment, will be key to support the appropriate investments and policy changes. In this Personal View, we discuss the potential role of HIV drug resistance testing for population-based surveillance and individual patient management in sub-Saharan Africa. We review the strengths and challenges of promising low-cost technologies and how they can be implemented. Copyright © 2016 Elsevier Ltd. All rights reserved.

RNA Editing and Drug Discovery for Cancer Therapy

Directory of Open Access Journals (Sweden)

Wei-Hsuan Huang

2013-01-01

Full Text Available RNA editing is vital to provide the RNA and protein complexity to regulate the gene expression. Correct RNA editing maintains the cell function and organism development. Imbalance of the RNA editing machinery may lead to diseases and cancers. Recently, RNA editing has been recognized as a target for drug discovery although few studies targeting RNA editing for disease and cancer therapy were reported in the field of natural products. Therefore, RNA editing may be a potential target for therapeutic natural products. In this review, we provide a literature overview of the biological functions of RNA editing on gene expression, diseases, cancers, and drugs. The bioinformatics resources of RNA editing were also summarized.

Hyperspherical Manifold for EEG Signals of Epileptic Seizures

Directory of Open Access Journals (Sweden)

Tahir Ahmad

2012-01-01

Full Text Available The mathematical modelling of EEG signals of epileptic seizures presents a challenge as seizure data is erratic, often with no visible trend. Limitations in existing models indicate a need for a generalized model that can be used to analyze seizures without the need for apriori information, whilst minimizing the loss of signal data due to smoothing. This paper utilizes measure theory to design a discrete probability measure that reformats EEG data without altering its geometric structure. An analysis of EEG data from three patients experiencing epileptic seizures is made using the developed measure, resulting in successful identification of increased potential difference in portions of the brain that correspond to physical symptoms demonstrated by the patients. A mapping then is devised to transport the measure data onto the surface of a high-dimensional manifold, enabling the analysis of seizures using directional statistics and manifold theory. The subset of seizure signals on the manifold is shown to be a topological space, verifying Ahmad's approach to use topological modelling.

Behavioral problems of siblings of epileptic children in Enugu ...

African Journals Online (AJOL)

Materials and Methods: Epileptic patients who consecutively referred to the Pediatric Neurology Clinic of the University of Nigeria Teaching Hospital, Enugu, from October 1999 to September 2000 were recruited. Demographic data were obtained, with a questionnaire administered to the parents. Information on the behavior ...

Early antiretroviral therapy and potent second-line drugs could decrease HIV incidence of drug resistance.

Science.gov (United States)

Shen, Mingwang; Xiao, Yanni; Rong, Libin; Meyers, Lauren Ancel; Bellan, Steven E

2017-06-28

Early initiation of antiretroviral therapy (ART) reduces the risk of drug-sensitive HIV transmission but may increase the transmission of drug-resistant HIV. We used a mathematical model to estimate the long-term population-level benefits of ART and determine the scenarios under which earlier ART (treatment at 1 year post-infection, on average) could decrease simultaneously both total and drug-resistant HIV incidence (new infections). We constructed an infection-age-structured mathematical model that tracked the transmission rates over the course of infection and modelled the patients' life expectancy as a function of ART initiation timing. We fitted this model to the annual AIDS incidence and death data directly, and to resistance data and demographic data indirectly among men who have sex with men (MSM) in San Francisco. Using counterfactual scenarios, we assessed the impact on total and drug-resistant HIV incidence of ART initiation timing, frequency of acquired drug resistance, and second-line drug effectiveness (defined as the combination of resistance monitoring, biomedical drug efficacy and adherence). Earlier ART initiation could decrease the number of both total and drug-resistant HIV incidence when second-line drug effectiveness is sufficiently high (greater than 80%), but increase the proportion of new infections that are drug resistant. Thus, resistance may paradoxically appear to be increasing while actually decreasing. © 2017 The Author(s).

Non-Steroidal Anti-inflammatory Drugs As Host-Directed Therapy for Tuberculosis: A Systematic Review

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Vera M. Kroesen

2017-06-01

Full Text Available Lengthy, antimicrobial therapy targeting the pathogen is the mainstay of conventional tuberculosis treatment, complicated by emerging drug resistances. Host-directed therapies, including non-steroidal anti-inflammatory drugs (NSAIDs, in contrast, target host factors to mitigate disease severity. In the present Systematic Review, we investigate whether NSAIDs display any effects as therapy of TB and discuss possible mechanisms of action of NSAIDs as adjunctive therapy of TB. Ten studies, seven preclinical studies in mice and three clinical trials, were included and systematically reviewed. Our results point toward a beneficial effect of NSAIDs as adjunct to current TB therapy regimens, mediated by decreased lung pathology balancing host-immune reaction. The determination of the best timing for their administration in order to obtain the potential beneficial effects needs further investigation. Even if the preclinical evidence requires clinical evaluation, NSAIDs might represent a potential safe, simple, and cheap improvement in therapy of TB.

Chitosan in Mucoadhesive Drug Delivery: Focus on Local Vaginal Therapy

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Toril Andersen

2015-01-01

Full Text Available Mucoadhesive drug therapy destined for localized drug treatment is gaining increasing importance in today’s drug development. Chitosan, due to its known biodegradability, bioadhesiveness and excellent safety profile offers means to improve mucosal drug therapy. We have used chitosan as mucoadhesive polymer to develop liposomes able to ensure prolonged residence time at vaginal site. Two types of mucoadhesive liposomes, namely the chitosan-coated liposomes and chitosan-containing liposomes, where chitosan is both embedded and surface-available, were made of soy phosphatidylcholine with entrapped fluorescence markers of two molecular weights, FITC-dextran 4000 and 20,000, respectively. Both liposomal types were characterized for their size distribution, zeta potential, entrapment efficiency and the in vitro release profile, and compared to plain liposomes. The proof of chitosan being both surface-available as well as embedded into the liposomes in the chitosan-containing liposomes was found. The capability of the surface-available chitosan to interact with the model porcine mucin was confirmed for both chitosan-containing and chitosan-coated liposomes implying potential mucoadhesive behavior. Chitosan-containing liposomes were shown to be superior in respect to the simplicity of preparation, FITC-dextran load, mucoadhesiveness and in vitro release and are expected to ensure prolonged residence time on the vaginal mucosa providing localized sustained release of entrapped model substances.

Promise and deceit: pharmakos, drug replacement therapy, and the perils of experience.

Science.gov (United States)

Meyers, Todd

2014-06-01

The problem of lying as a feature of medication compliance has been well documented in anthropological and clinical literatures. Yet the role of the lie-its destabilizing effects on the continuity of drug treatment and therapy, as a technology of drug misuse, or as a way to understand the neuro-chemical processes of treatment (pharmacotherapy "tricking" or lying to the brain)-has been less considered, particularly in the context of opioid replacement therapy. The following paper is set against the backdrop of a three-year study of adolescents receiving a relatively new drug (buprenorphine) for the treatment of opiate dependency inside and outside of highly monitored treatment environments in the United States. Lies give order not only to the experience of addiction but also to the experience of therapy as well. In order to better understand this ordering of experience, the paper puts the widely discussed conceptual duality of the pharmakon (healing and poison) in conversation with a perilously overlooked subject in the critical study of pharmacotherapy, namely the pharmakos or the personification of sacrifice. The paper demonstrates how the patient-subject comes to represent therapeutic promise by allowing for the possibility of (and often performing) deceit.

Effect Of Cognitive Stimulation On Hippocampal Ripples In Epileptic Patients

Czech Academy of Sciences Publication Activity Database

Brázdil, M.; Cimbálník, J.; Roman, R.; Stead, M.; Daniel, P.; Halámek, Josef; Jurák, Pavel

2013-01-01

Roč. 54, S3 (2013), s. 268-268 ISSN 0013-9580. [International Epilepsy Congress /30./. 23.06.2013-27.06.2013, Montreal] Institutional support: RVO:68081731 Keywords : Cognitive Stimulation * Epileptic Patients Subject RIV: FH - Neurology

Drug Therapy.

Science.gov (United States)

He, Ri-Hui; Tao, Ran

2017-01-01

This chapter first summarizes the therapy of addiction disorder, and elaborates on the progress of medication. First, the difference between dependency and addiction are introduced. The basic principles of the therapy of substance and non-substance addiction are then put forward. It is also pointed out in this chapter that with the progress of the study, the goal of addiction disorder therapy is expected to transfer from reducing the relapse and harm of the addiction to completely eliminating and recovering from it. This chapter also introduces the progress of psychological addiction elimination technology, especially the "Unconditioned Stimulus Retrieval Extinction Paradigm and Conditioned Stimulus Retrieval Extinction Paradigm" and PITDH technology. Finally it is pointed out that in addiction disorder therapy, comprehensive intervention has become a trend. With regard to the medication for addiction disorders, this chapter also includes the progress and deficiencies of substance and non-substance addiction. In terms of addiction disorder rehabilitation, the foundation of substance addiction is medication which is, however, limited for non-substance addiction. The key to the rehabilitation of addiction disorder is psycho-behavioral therapy, which is especially effective in eliminating craving.

Cancer therapy leading to state of cancer metabolism depression for efficient operation of small dosage cytotoxic drugs

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Ponizovskiy MR

2015-04-01

Full Text Available “Prolonged medical starvation” as the method of cancer therapy was borrowed from folk healers Omelchenko A and Breuss R. Author was convinced in efficiency of this method of cancer treatment via examination of cured patients and on own experience. The mechanism of this method of cancer therapy operates via Warburg effect targeting that promotes efficient cancer treatment with small cytotoxic drugs. Just it was described the mechanism of Warburg effect as well as mechanism transmutation of mitochondrial function in cancer metabolism which are exhibited in connection with operation of described method cancer therapy. There were described the biochemical and biophysical mechanisms of formations resistance to some cytotoxic drugs and recurrence cancer disease after disease remission which occur sometimes as result of treatment with great dosage of cytotoxic drugs. Also it was described the benefits of use the method “Prolonged medical starvation” with decreased dosage of cytotoxic drugs for cancer treatment. The significance of this work that it was substantiated the mechanism operation of combination “Prolonged medical starvation” with small dosages cytotoxic drugs of cancer treatment, which mechanism leads to prevention recurrence cancer disease and resistance to anticancer drugs in comparison with intensive anticancer chemotherapy with great dosages of cytotoxic drugs in cancer therapy. Also the offered concepts of cancer therapy mechanism gave possibility to explain mechanisms of some results of experiments eliminating the doubts of the authors these experiments.

Behavioral couples therapy (BCT) for alcohol and drug use disorders: A meta-analysis

NARCIS (Netherlands)

Powers, M.B.; Vedel, E.; Emmelkamp, P.M.G.

2008-01-01

Narrative reviews conclude that behavioral couples therapy (BCT) produces better outcomes than individual-based treatment for alcoholism and drug abuse problems (e.g., [Epstein, E. E., & McCrady, B. S. (1998). Behavioral couples treatment of alcohol and drug use disorders: Current status and

Continuous Drug Infusion for Diabetes Therapy: A Closed-Loop Control System Design

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Jiming Chen

2008-03-01

Full Text Available While a typical way for diabetes therapy is discrete insulin infusion based on long-time interval measurement, in this paper, we design a closed-loop control system for continuous drug infusion to improve the traditional discrete methods and make diabetes therapy automatic in practice. By exploring the accumulative function of drug to insulin, a continuous injection model is proposed. Based on this model, proportional-integral-derivative (PID and fuzzy logic controllers are designed to tackle a control problem of the resulting highly nonlinear plant. Even with serious disturbance of glucose, such as nutrition absorption at meal time, the proposed scheme can perform well in simulation experiments.

NIR photoregulated chemo- and photodynamic cancer therapy based on conjugated polyelectrolyte-drug conjugate encapsulated upconversion nanoparticles

Science.gov (United States)

Yuan, Youyong; Min, Yuanzeng; Hu, Qinglian; Xing, Bengang; Liu, Bin

2014-09-01

The design of nanoplatforms with target recognition and near-infrared (NIR) laser photoregulated chemo- and photodynamic therapy is highly desirable but remains challenging. In this work, we have developed such a system by taking advantage of a conjugated polyelectrolyte (CPE)-drug conjugate and upconversion nanoparticles (UCNPs). The poly(ethylene glycol) (PEG) grafted CPE not only serves as a polymer matrix for UCNP encapsulation, but also as a fluorescent imaging agent, a photosensitizer as well as a carrier for chemotherapeutic drug doxorubicin (DOX) through a UV-cleavable ortho-nitrobenzyl (NB) linker. Upon 980 nm laser irradiation, the UCNPs emit UV and visible light. The up-converted UV light is utilized for controlled drug release through the photocleavage of the ortho-nitrobenzyl linker, while the up-converted visible light is used to initiate the polymer photosensitizer to produce reactive oxygen species (ROS) for photodynamic therapy. The NIR photo-regulated UCNP@CPE-DOX showed high efficiency of ROS generation and controlled drug release in cancer cells upon single laser irradiation. In addition, the combination therapy showed enhanced inhibition of U87-MG cell growth as compared to sole treatments. As two light sources with different wavelengths are always needed for traditional photodynamic therapy and photoregulated drug release, the adoption of UCNPs as an NIR light switch is highly beneficial to combined chemo- and photodynamic therapy with enhanced therapeutic effects.

Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy

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Warangkana Lohcharoenkal

2014-01-01

Full Text Available Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy.

Protein nanoparticles as drug delivery carriers for cancer therapy.

Science.gov (United States)

Lohcharoenkal, Warangkana; Wang, Liying; Chen, Yi Charlie; Rojanasakul, Yon

2014-01-01

Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy.

Epilepsy, anti-epileptic medication use and risk of cancer

DEFF Research Database (Denmark)

Kaae, Jeanette; Carstensen, Lisbeth; Wohlfahrt, Jan

2014-01-01

Whether the powerful medications used to treat epilepsy increase the risk of cancer has been debated for decades, but until now no study could disentangle the contributions of anti-epileptic medications and epilepsy itself to cancer risk. Using a cohort comprising all Danish residents ≥ 16 years ...

On the slow diffusion of Point of Care systems in Therapeutic Drug Monitoring

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Barbara eSanavio

2015-02-01

Full Text Available Recent advancements in point-of-care technologies show great transformative promises for personalized preventative and predictive medicine. However, fields like therapeutic drug monitoring, that first allowed for personalized treatment of patient’ disease, still lag behind in the widespread application of point-of-care devices for monitoring of patients. Surprisingly, very few applications in commonly monitored drugs, such as anti-epileptics, are paving the way for a point of care (PoC approach to patient’ therapy monitoring, compared to other fields –like intensive care cardiac markers monitoring, glycemic controls in diabetes, or bench-top hematological parameters analysis at the local drug store. Such delay in the development of portable fast clinically effective drug monitoring devices is in our opinion due more to an inertial drag on the pervasiveness of these new devices into the clinical field than a lack of technical capability. At the same time, some very promising technologies failed in the clinical practice for inadequate understanding of the outcome parameters necessary for a relevant technological breakthrough that has superior clinical performance. We hope, by overviewing both therapeutic drug monitoring practice and its yet unmet needs and latest advancement in micro and nanotechnology applications to PoC clinical devices, to help bridging the two communities, the one exploiting analytical technologies and the one mastering the most advanced techniques, into translating existing and forthcoming technologies in effective devices.

Health care costs of adults treated for attention-deficit/hyperactivity disorder who received alternative drug therapies.

Science.gov (United States)

Wu, Eric Q; Birnbaum, Howard G; Zhang, Huabin F; Ivanova, Jasmina I; Yang, Elaine; Mallet, David

2007-09-01

Many therapies exist for treating adult attention-deficit/hyperactivity disorder (ADHD), also referred to as attention-deficit disorder (ADD), but there is no research regarding cost differences associated with initiating alternative ADD/ADHD drug therapies in adults. To compare from the perspective of a large self-insured employer the risk-adjusted direct health care costs associated with 3 alternative drug therapies for ADD in newly treated patients: extended-release methylphenidate (osmotic release oral system-MPH), mixed amphetamine salts extended release (MAS-XR), or atomoxetine. We analyzed data from a US claims database of 5 million beneficiaries from 31 large self-insured employers (1999-2004). Analysis was restricted to adults aged 18 to 64 years with at least 1 diagnosis of ADD/ADHD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 314.0x--attention deficit disorder; 314.00--attention deficit disorder without hyperactivity; or 314.01--attention-deficit disorder with hyperactivity) and at least 1 pharmacy claim for OROS-MPH, MAS-XR, or atomoxetine identified using National Drug Codes. In preliminary analysis, we calculated the duration of index ADHD drug therapy as time from index therapy initiation to a minimum 60-day gap. Because the median duration of index ADHD drug therapy was found to be approximately 90 days, the primary measures were total direct medical plus drug costs and medical-only costs computed over 6 months following therapy initiation. Adults were required to have continuous eligibility 6 months before and 6 months after their latest drug therapy initiation and no ADHD therapy during the previous 6 months. Cost was measured as the payment amount made by the health plan to the provider rather than billed charges, and it excluded patient copayments and deductibles. Medical costs included costs incurred for all-cause inpatient and outpatient/other services. Costs were adjusted for inflation to

Nanotechnology-Based Drug Delivery Systems for Photodynamic Therapy of Cancer: A Review.

Science.gov (United States)

Calixto, Giovana Maria Fioramonti; Bernegossi, Jéssica; de Freitas, Laura Marise; Fontana, Carla Raquel; Chorilli, Marlus

2016-03-11

Photodynamic therapy (PDT) is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS) is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs) with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug delivery systems, such as polymeric nanoparticles (PNPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), gold nanoparticles (AuNPs), hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin is a potential strategy to overcome this difficulty. Additionally, nanotechnology-based drug delivery systems may improve the transcytosis of a PS across epithelial and endothelial barriers and afford the simultaneous co-delivery of two or more drugs. Based on this, the application of nanotechnology in medicine may offer numerous exciting possibilities in cancer treatment and improve the efficacy of available therapeutics. Therefore, the aim of this paper is to review nanotechnology-based drug delivery systems for photodynamic therapy of cancer.

Nanotechnology-Based Drug Delivery Systems for Photodynamic Therapy of Cancer: A Review

Directory of Open Access Journals (Sweden)

Giovana Maria Fioramonti Calixto

2016-03-01

Full Text Available Photodynamic therapy (PDT is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug delivery systems, such as polymeric nanoparticles (PNPs, solid lipid nanoparticles (SLNs, nanostructured lipid carriers (NLCs, gold nanoparticles (AuNPs, hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin is a potential strategy to overcome this difficulty. Additionally, nanotechnology-based drug delivery systems may improve the transcytosis of a PS across epithelial and endothelial barriers and afford the simultaneous co-delivery of two or more drugs. Based on this, the application of nanotechnology in medicine may offer numerous exciting possibilities in cancer treatment and improve the efficacy of available therapeutics. Therefore, the aim of this paper is to review nanotechnology-based drug delivery systems for photodynamic therapy of cancer.

Skeletal mass in patients receiving chronic anticonvulsant therapy

Energy Technology Data Exchange (ETDEWEB)

Zanzi, I.; Roginsky, M.S.; Rosen, A.; Cohn, S.H.

1981-01-01

The technique of in vivo total body neutron activation analysis was used to measure total body calcium (TBCa), a sensitive and precise index of skeletal mass, expressed as the Ca ratio (TBCa observed/TBCa predicted). 23 unselected, ambulatory, noninstitutionalized, adult epileptic patients under long-term anticonvulsant therapy were studied. Ca ratio was normal in 20 of the patients, low in only 2 and borderline in 1 patient. Plasma alkaline phosphatase values were elevated in half the subjects. Plasma Ca (uncorrected) was in the normal range in all. Serum 25-hydroxvitamin D (25-OHD) was low in 67% of the subjects, but only 1 patient had a value below 5 ng/ml. There was no correlation between the Ca ratio and the alkaline phosphatase or 25-OHD values. No radiographic or other evidences of osteomalacia were observed. This study does not support the notion of a prevalence of osteopenia in ambulatory, noninstitutionalized, adult epileptic patients receiving chronic anticonvulsant therapy in this geographical area despite the frequent findings of biochemical abnormalities.

A Penalized Semialgebraic Deflation ICA Algorithm for the Efficient Extraction of Interictal Epileptic Signals.

Science.gov (United States)

Becker, Hanna; Albera, Laurent; Comon, Pierre; Kachenoura, Amar; Merlet, Isabelle

2017-01-01

As a noninvasive technique, electroencephalography (EEG) is commonly used to monitor the brain signals of patients with epilepsy such as the interictal epileptic spikes. However, the recorded data are often corrupted by artifacts originating, for example, from muscle activities, which may have much higher amplitudes than the interictal epileptic signals of interest. To remove these artifacts, a number of independent component analysis (ICA) techniques were successfully applied. In this paper, we propose a new deflation ICA algorithm, called penalized semialgebraic unitary deflation (P-SAUD) algorithm, that improves upon classical ICA methods by leading to a considerably reduced computational complexity at equivalent performance. This is achieved by employing a penalized semialgebraic extraction scheme, which permits us to identify the epileptic components of interest (interictal spikes) first and obviates the need of extracting subsequent components. The proposed method is evaluated on physiologically plausible simulated EEG data and actual measurements of three patients. The results are compared to those of several popular ICA algorithms as well as second-order blind source separation methods, demonstrating that P-SAUD extracts the epileptic spikes with the same accuracy as the best ICA methods, but reduces the computational complexity by a factor of 10 for 32-channel recordings. This superior computational efficiency is of particular interest considering the increasing use of high-resolution EEG recordings, whose analysis requires algorithms with low computational cost.

Mozart k.545 mimics mozart k.448 in reducing epileptiform discharges in epileptic children.

Science.gov (United States)

Lin, Lung-Chang; Lee, Mei-Wen; Wei, Ruey-Chang; Mok, Hin-Kiu; Wu, Hui-Chuan; Tsai, Chin-Lin; Yang, Rei-Cheng

2012-01-01

Mozart K.448 has been shown to improve cognitive function, leading to what is known as the Mozart Effect. Our previous work reveals positive effects of Mozart K.448 in reducing epileptiform discharges in epileptic children. In this study, we evaluated the effect of Mozart K.545 and compared the effects with those of Mozart K.448 on epileptiform discharges in children with epilepsy. Thirty-nine epileptic children with epileptiform discharges were included in the study. They received electroencephalogram examinations before, during, and after listening to Mozart K.448 and K.545, one week apart, respectively. The frequencies of epileptiform discharges were compared. There was a significant decrease in the frequency of epileptiform discharges during and right after listening to Mozart K.448 and K.545 (reduced by 35.7 ± 32.7% during Mozart K.448 and 30.3 ± 44.4% after Mozart K.448; and 34.0 ± 39.5% during Mozart K.545 and 31.8 ± 39.2% after Mozart K.545). Spectrogrammatic analysis of the two pieces of music demonstrated that both share similar spectrogrammatic characteristics. Listening to Mozart K.448 and K.545 decreased the epileptiform discharges in epileptic children. This suggests that Mozart K.448 is not the only piece of music to have beneficial effects on children with epilepsy. Other music with lower harmonics may also decrease epileptiform discharges in epileptic children.

Radioiodine therapy versus antithyroid drugs in Graves' disease: a meta-analysis of randomized controlled trials

Science.gov (United States)

Qin, Lan

2016-01-01

Objective: This meta-analysis was performed to compare radioiodine therapy with antithyroid drugs in terms of clinical outcomes, including development or worsening of ophthalmopathy, hyperthyroid cure rate, hypothyroidism, relapse rate and adverse events. Methods: Randomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, SinoMed and National Knowledge Infrastructure, China, were systematically reviewed to compare the effects of radioiodine therapy with antithyroid drugs in patients with Graves' disease. Results were expressed as risk ratio with 95% confidence intervals (CIs) and weighted mean differences with 95% CIs. Pooled estimates were performed using a fixed-effects model or random-effects model, depending on the heterogeneity among studies. Results: 17 RCTs involving 4024 patients met the inclusion criteria and were included. Results showed that radioiodine treatment has increased risk in new ophthalmopathy, development or worsening of ophthalmopathy and hypothyroidism. Whereas, compared with antithyroid drugs, radioiodine treatment seems to have a higher hyperthyroid cure rate, lower recurrence rate and lower incidence of adverse events. Conclusion: Radioiodine therapy is associated with a higher hyperthyroid cure rate and lower relapse rate compared with antithyroid drugs. However, it also increases the risk of ophthalmopathy and hypothyroidism. Advances in knowledge: Considering that antithyroid drug treatment can be associated with unsatisfactory control of hyperthyroidism, we would recommend radioiodine therapy as the treatment of choice for patients with Graves' disease. PMID:27266544

Elevated VGKC-Complex Antibodies in a Boy with Fever-Induced Refractory Epileptic Encephalopathy in School-Age Children (FIRES)

Science.gov (United States)

Illingworth, Marjorie A.; Hanrahan, Donncha; Anderson, Claire E.; O'Kane, Kathryn; Anderson, Jennifer; Casey, Maureen; de Sousa, Carlos; Cross, J. Helen; Wright, Sukvhir; Dale, Russell C.; Vincent, Angela; Kurian, Manju A.

2011-01-01

Fever-induced refractory epileptic encephalopathy in school-age children (FIRES) is a clinically recognized epileptic encephalopathy of unknown aetiology. Presentation in previously healthy children is characterized by febrile status epilepticus. A pharmacoresistant epilepsy ensues, occurring in parallel with dramatic cognitive decline and…

Current status of the New Antiepileptic drugs in chronic pain.

Directory of Open Access Journals (Sweden)

Harpreet Singh Sidhu

2016-08-01

Full Text Available Antiepileptic drugs (AEDs are extensively used worldwide to treat a wide range of disorders other than epilepsy, such as neuropathic pain, migraine and bipolar disorder. Due to this situation more than 20 new third-generation AEDs have been introduced in the market recently. The future design of new AEDs must also have potential to help in the non-epileptic disorders. The wide acceptance of second generation AEDs for the management of various Non-epileptic disorders has caused the emergence of generics in the market. The wide use of approved AEDs outside epilepsy is based on both economic and scientific reasons. Bipolar disorders, migraine prophylaxis, fibromyalgia and neuropathic pain represent the most attractive indication expansion opportunities for anticonvulsant developers, providing blockbuster revenues. Strong growth in non-epilepsy conditions will see Pfizer’s Lyrica become the market leading brand by 2018. In this review we mainly focus on the current status of new AEDs in the treatment of chronic pain and migraine prophylaxis. AEDs have a strong analgesic potential and this is demonstrated by the wide use of carbamazepine in trigeminal neuralgia and sodium valproate in migraine prophylaxis. At present, data on the new AEDs for non-epileptic conditions are inconclusive. Not all AEDs are effective in the management of neuropathic pain and migraine. Only those AEDs whose mechanisms of action are match with pathophysiology of the disease, have potential to show efficacy in non-epileptic disorder. For this better understanding of the pathophysiology of the disease and mechanisms of action of new AEDs are essential requirement before initiating pre-clinical and clinical trials. Many new AEDs show good results in the animal model and open-label studies but fail to provide strong evidence at randomized, placebo-controlled trials. The final decision regarding the clinical efficacy of the particular AEDs in a specific non-epileptic disorder

The determinants of seizure severity in Nigerian epileptics | Imam ...

African Journals Online (AJOL)

This assesses generalisation of seizures, falls, injuries, urinary incontinence, warning interval before loss of consciousness, automatisms and time of recovery on a graded scale. Results: The most frequent indices of seizure severity in Nigerian epileptics is the generalisation of seizures in 85.7% of subjects, incontinence of ...

Sleep deprivation and spike-wave discharges in epileptic rats

NARCIS (Netherlands)

Drinkenburg, W.H.I.M.; Coenen, A.M.L.; Vossen, J.M.H.; Luijtelaar, E.L.J.M. van

1995-01-01

The effects of sleep deprivation were studied on the occurrence of spike-wave discharges in the electroencephalogram of rats of the epileptic WAG/Rij strain, a model for absence epilepsy. This was done before, during and after a period of 12 hours of near total sleep deprivation. A substantial

Novel concept of the smart NIR-light-controlled drug release of black phosphorus nanostructure for cancer therapy.

Science.gov (United States)

Qiu, Meng; Wang, Dou; Liang, Weiyuan; Liu, Liping; Zhang, Yin; Chen, Xing; Sang, David Kipkemoi; Xing, Chenyang; Li, Zhongjun; Dong, Biqin; Xing, Feng; Fan, Dianyuan; Bao, Shiyun; Zhang, Han; Cao, Yihai

2018-01-16

A biodegradable drug delivery system (DDS) is one the most promising therapeutic strategies for cancer therapy. Here, we propose a unique concept of light activation of black phosphorus (BP) at hydrogel nanostructures for cancer therapy. A photosensitizer converts light into heat that softens and melts drug-loaded hydrogel-based nanostructures. Drug release rates can be accurately controlled by light intensity, exposure duration, BP concentration, and hydrogel composition. Owing to sufficiently deep penetration of near-infrared (NIR) light through tissues, our BP-based system shows high therapeutic efficacy for treatment of s.c. cancers. Importantly, our drug delivery system is completely harmless and degradable in vivo. Together, our work proposes a unique concept for precision cancer therapy by external light excitation to release cancer drugs. If these findings are successfully translated into the clinic, millions of patients with cancer will benefit from our work.

Classifying epileptic EEG signals with delay permutation entropy and Multi-Scale K-means.

Science.gov (United States)

Zhu, Guohun; Li, Yan; Wen, Peng Paul; Wang, Shuaifang

2015-01-01

Most epileptic EEG classification algorithms are supervised and require large training datasets, that hinder their use in real time applications. This chapter proposes an unsupervised Multi-Scale K-means (MSK-means) MSK-means algorithm to distinguish epileptic EEG signals and identify epileptic zones. The random initialization of the K-means algorithm can lead to wrong clusters. Based on the characteristics of EEGs, the MSK-means MSK-means algorithm initializes the coarse-scale centroid of a cluster with a suitable scale factor. In this chapter, the MSK-means algorithm is proved theoretically superior to the K-means algorithm on efficiency. In addition, three classifiers: the K-means, MSK-means MSK-means and support vector machine (SVM), are used to identify seizure and localize epileptogenic zone using delay permutation entropy features. The experimental results demonstrate that identifying seizure with the MSK-means algorithm and delay permutation entropy achieves 4. 7 % higher accuracy than that of K-means, and 0. 7 % higher accuracy than that of the SVM.

Cost-utility analysis of antithyroid drug therapy versus 131I therapy for Graves' disease

International Nuclear Information System (INIS)

Hayashi, Katsumi; Abe, Katsumi; Sakata, Ikuko; Sakaguchi, Chiharu; Yamamoto, Kentaro; Kosuda, Shigeru

2005-01-01

There is no comparative cost-utility study between 131 I therapy and antithyroid drugs (ATD) therapy for Graves' disease, though 131 I therapy has higher remission rate and less side effects. The objective of the study was to analyze the cost-utility of ATD therapy versus 131 I therapy by calculating life-long medical costs and utility, based on the responses of Graves' disease patients to questionnaires. To determine the expected cost and expected utility, a decision tree analysis was designed on the basis of the 2 competing strategies of ATD therapy versus 131 I therapy. A simulation of 1,000 female patients weighing≥50 kg who assumed to experience the onset of Graves' disease at the age of 30, to first complain of thyrotoxic symptoms and moderate goiter 2-3 mo. previously, and to undergo a 40-years-long cohort study, was created for each strategy using a decision tree and baselines of other relevant variables. The variables and costs were based on the literature and hospital bills. The maximum and minimum values of utility were defined as 1.0 and 0.0, respectively. Future costs and utilities were discounted 5%. The medical costs and utilities were 85,739-88,650 yen/patient/40 years and 16.47-16.56/patient/40 years, respectively, for the ATD therapy strategy, and 81,842 yen/patient/40 years and 17.41/patient/40 years, respectively, for the 131 I therapy strategy. These results quantitatively demonstrated that the 131 I therapy strategy was superior to the ATD therapy strategy in terms of both cost and utility. 131 I therapy should be used more widely in Japan because of its greater utility and lower cost. (author)

Study of urinary 6 beta-hydroxycortisol/cortisol ratio in spot urine sample as a biomarker of 3A4 enzyme activity in healthy and epileptic subjects of Egyptian population.

Science.gov (United States)

El Desoky, Ehab S; Mohamed, Hanan O; Farghaly, Wafaa M A; Hamed, Sherifa A; Hedaya, Mohsen A; Siest, Jean-Pascal

2005-06-01

The ratio of urinary 6 beta-hydroxycortisol/cortisol (6 beta-OHC/FC) in morning spot urine samples collected from 8:00 a.m. to 12:00 p.m. was studied using ELIZA kits (Stabiligen) in a group of healthy adult Egyptians (control group) of both sex (n=65, age range: 16-48 years). The frequency distribution of urinary 6 beta-OHC/FC ratio was widely distributed among subjects with higher values in males in comparison to females. No bimodality in either sex was observed. Another group of adult epileptic patients (n=16) was studied for the influence of chronic carbamazepine antiepileptic drug administration on urinary 6 beta-OHC/FC ratio in spot urine samples. The induction property of carbamazepine on CYP3A4 was observed through significant increase (p=0.01) in 6 beta-OHC/FC ratio among epileptic patients in comparison with control subjects. In conclusion, the frequency distribution of urinary 6 beta-OHC/FC ratio among Egyptians shows sexual dimorphism. Also, measurement of urinary 6 beta-OHC/FC ratio provides a simple non-invasive method to monitor CYP3A4 enzyme induction during administration of carbamazepine antiepileptic drug.

Antibody-drug conjugates: Promising and efficient tools for targeted cancer therapy.

Science.gov (United States)

Nasiri, Hadi; Valedkarimi, Zahra; Aghebati-Maleki, Leili; Majidi, Jafar

2018-09-01

Over the recent decades, the use of antibody-drug conjugates (ADCs) has led to a paradigm shift in cancer chemotherapy. Antibody-based treatment of various human tumors has presented dramatic efficacy and is now one of the most promising strategies used for targeted therapy of patients with a variety of malignancies, including hematological cancers and solid tumors. Monoclonal antibodies (mAbs) are able to selectively deliver cytotoxic drugs to tumor cells, which express specific antigens on their surface, and has been suggested as a novel category of agents for use in the development of anticancer targeted therapies. In contrast to conventional treatments that cause damage to healthy tissues, ADCs use mAbs to specifically attach to antigens on the surface of target cells and deliver their cytotoxic payloads. The therapeutic success of future ADCs depends on closely choosing the target antigen, increasing the potency of the cytotoxic cargo, improving the properties of the linker, and reducing drug resistance. If appropriate solutions are presented to address these issues, ADCs will play a more important role in the development of targeted therapeutics against cancer in the next years. We review the design of ADCs, and focus on how ADCs can be exploited to overcome multiple drug resistance (MDR). © 2018 Wiley Periodicals, Inc.

Evaluation of SPECT with N-isopropyl[I-123]-p-iodoamphetamine (IMP) in epileptic patients

International Nuclear Information System (INIS)

Nambu, Toshikazu; Itoh, Kazuo; Sumi, Tetsuo; Furudate, Masayori; Irie, Goro

1988-01-01

Brain SPECT scintigrams with N-Isopropyl[I-123]-p-Iodoamphetamine (IMP) were reviewed and compared with the EEG findings in 21 epileptic patients (22 SPECT images) with normal CT. Thirteen of 22 SPECT images showed abnormal low uptake and 7 of them corresponded to the EEG focus. In order to obtain the quantitative analysis, the count ratio of the focus side to the opposite I-123 content in fixed ROI was measured for each case, but no statistically significant correlation for the frequency or the duration of epilepsy was found. EEG is not considered to be favorite standard for localizing epileptic foci, especially in deep cerebral region, and that may be one of the main reason for the incomplete correlation. In the qualitative study, however, the cases with frequent epileptic attack were more likely to show abnormal findings. I-123 IMP SPECT can now be considered as having a significant clinical role for the diagnosis and management of patients with epilepsy. (author)

Gene therapy decreases seizures in a model of Incontinentia pigmenti.

Science.gov (United States)

Dogbevia, Godwin K; Töllner, Kathrin; Körbelin, Jakob; Bröer, Sonja; Ridder, Dirk A; Grasshoff, Hanna; Brandt, Claudia; Wenzel, Jan; Straub, Beate K; Trepel, Martin; Löscher, Wolfgang; Schwaninger, Markus

2017-07-01

Incontinentia pigmenti (IP) is a genetic disease leading to severe neurological symptoms, such as epileptic seizures, but no specific treatment is available. IP is caused by pathogenic variants that inactivate the Nemo gene. Replacing Nemo through gene therapy might provide therapeutic benefits. In a mouse model of IP, we administered a single intravenous dose of the adeno-associated virus (AAV) vector, AAV-BR1-CAG-NEMO, delivering the Nemo gene to the brain endothelium. Spontaneous epileptic seizures and the integrity of the blood-brain barrier (BBB) were monitored. The endothelium-targeted gene therapy improved the integrity of the BBB. In parallel, it reduced the incidence of seizures and delayed their occurrence. Neonate mice intravenously injected with the AAV-BR1-CAG-NEMO vector developed no hepatocellular carcinoma or other major adverse effects 11 months after vector injection, demonstrating that the vector has a favorable safety profile. The data show that the BBB is a target of antiepileptic treatment and, more specifically, provide evidence for the therapeutic benefit of a brain endothelial-targeted gene therapy in IP. Ann Neurol 2017;82:93-104. © 2017 American Neurological Association.

Pancreatitis associated with potassium bromide/phenobarbital combination therapy in epileptic dogs.

OpenAIRE

Gaskill, C L; Cribb, A E

2000-01-01

In a retrospective study, at least 10% of dogs receiving potassium bromide/phenobarbital combination therapy, compared with 0.3% of dogs receiving phenobarbital monotherapy, had probable pancreatitis. Pancreatitis may be a more frequent and more serious adverse effect of potassium bromide/phenobarbital combination therapy than has been reported previously.

Effects of aerobic exercise and drug therapy on blood pressure and ...

African Journals Online (AJOL)

EB

Key words: Aerobic exercise, drug therapy, blood pressure, randomised controlled trial. African Health Sciences 2013; (1): .... body fat and displayed it on the screen of the meter. ... inelastible tape measure (Butterfly, China). Blood pressure ...

Treating Women Drug Abusers: Action Therapy and Trauma Assessment

Science.gov (United States)

Uhler, Ann S.; Parker, Olga V.

2002-01-01

The authors suggest that action therapy, a group of techniques including psychodrama, drama therapy, and role training, warrants research attention to determine whether it is well suited to the special characteristics and needs of women clients. In addition, the authors call on researchers to develop a new standardized tool for counselors to use during initial interviews to determine whether women presenting for drug abuse treatment also have significant issues related to trauma. The authors believe the use of unassisted clinical judgment for trauma assessment in first interviews may drive patients away by probing for painful information that clients are not yet ready to confront or divulge. PMID:18567963

Assessment of patients' knowledge of their drug therapy in a ...

African Journals Online (AJOL)

Patients' knowledge of their medications is an important factor in ensuring adherence. Medication adherence is essential for rational drug use and derivation of optimal therapy. This study was conducted to assess knowledge of outpatients regarding their medications. A well structured questionnaire was administered to 200 ...

Bisphosphonate Treatment in Osteoporosis: Optimal Duration of Therapy and the Incorporation of a Drug Holiday.

Science.gov (United States)

Villa, Jordan C; Gianakos, Arianna; Lane, Joseph M

2016-02-01

Bisphosphonates are the most widely used treatment for osteoporosis. They accumulate in the bone for years, and therefore, their inhibitory effects on osteoclasts may persist after drug discontinuation. The ideal duration of therapy remains controversial. The purpose of this study is to review the literature to determine the (1) indications for drug holiday, (2) the duration of drug holiday, (3) the evaluation during drug holiday, and (4) the proper treatment and maintenance after drug holiday. A review of two electronic databases (PubMed/MEDLINE and EMBASE) was conducted using the term "(Drug holiday)," in January 29, 2015. Inclusion criteria were as follows: (1) clinical trials and case control, (2) human studies, (3) published in a peer-review journal, and (4) written in English. Exclusion criteria were as follows: (1) case reports, (2) case series, and (3) in vitro studies. The literature supports a therapeutic pause after 3-5 years of bisphosphonate treatment in patients with minor bone deficiencies and no recent fragility fracture (low risk) and in patients with moderate bone deficiencies and/or recent fragility fracture (moderate risk). In these patients, a bone health reevaluation is recommended every 1-3 years. Patients with high fracture risk should be maintained on bisphosphonate therapy without drug holiday. The duration and length of drug holiday should be individualized for each patient. Evaluation should be based on serial bone mass measurements, bone turnover rates, and fracture history evaluation. If after drug therapy, assessments show an increased risk of fracture, the patient may benefit from initiating another treatment. Raloxifene, teriparatide, or denosumab are available options.

Endogenous sulfur dioxide regulates hippocampal neuron apoptosis in developing epileptic rats and is associated with the PERK signaling pathway.

Science.gov (United States)

Niu, Manman; Han, Ying; Li, Qinrui; Zhang, Jing

2018-02-05

Epilepsy is among the most common neurological diseases in children. Recurrent seizures can result in hippocampal damage and seriously impair learning and memory functions in children. However, the mechanisms underlying epilepsy-related brain injury are unclear. Neuronal apoptosis is among the most common neuropathological manifestations of brain injury. Endogenous sulfur dioxide (SO 2 ) has been shown to be involved in seizures and related neuron apoptosis. However, the role of endogenous SO 2 in epilepsy remains unclear. This study assessed whether endogenous SO 2 is involved in epilepsy and its underlying mechanisms. Using a rat epilepsy model induced by an intraperitoneal injection of kainic acid (KA), we found that hippocampal neuron apoptosis was induced in epileptic rats, and the SO 2 content and aspartate aminotransferase (AAT) activity in the plasma were increased compared to those in the control group. However, the inhibition of SO 2 production by l-aspartate-β-hydroxamate (HDX) can subvert this response 72h after an epileptic seizure. No difference in apoptosis was observed 7 d after the epileptic seizure in the KA and KA+HDX groups. The protein expression levels of AAT2, glucose-regulated protein 78 (GRP78), pancreatic eIF2 kinase-like ER kinase (PERK) and phospho-PERK (p-PERK) were remarkably elevated in the hippocampi of the epileptic rats, while the HDX treatment was capable of reversing this process 7 d after the epileptic seizure. These results indicate that the inhibition of endogenous SO 2 production can alleviate neuronal apoptosis and is associated with the PERK signaling pathway during the initial stages after epileptic seizure, but inhibiting SO 2 production only delayed the occurrence of apoptosis and did not prevent neuronal apoptosis in the epileptic rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Direct anti-atherosclerotic therapy; development of natural anti-atherosclerotic drugs preventing cellular cholesterol retention.

Science.gov (United States)

Orekhov, Alexander N

2013-01-01

The results of numerous clinical trials with statins and other drugs have demonstrated the principal possibility of the prevention and regression of atherosclerosis by pharmacotherapy. This review describes the use of cultured human arterial cells for the mass screening of anti-atherosclerotic substances, the investigation of the mechanisms responsible for their atherosclerosis-related effects, and the optimization of anti-atherosclerotic and anti-atherogenic drug and dietary therapies. Natural products can be considered promising drugs for anti-atherosclerotic therapy. Our basic studies have shown that cellular lipidosis is the principal event in the genesis of atherosclerotic lesions. Using cellular models and natural products, we have developed an approach to prevent lipid accumulation in arterial cells. Based on our knowledge of atherosclerosis, we developed drugs that possess direct anti-atherosclerotic activity. Two-year treatment with allicor (garlic powder) has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Inflaminat (calendula, elder, and violet), which possesses anti-cytokine activity, has been shown to cause the regression of carotid atherosclerosis following the treatment of asymptomatic men for one year. The phytoestrogen-rich drug karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid) prevents the development of carotid atherosclerosis in postmenopausal women. Thus, our basic findings were successfully translated into clinical practice. Because of this translation, a novel approach to antiatherosclerotic therapy was developed. Our clinical trial confirmed the efficacy of both the novel approach and the novel drugs.

Cognitive-Behavioral Therapies for Young People in Outpatient Treatment for Nonopioid Drug Use

Science.gov (United States)

Filges, Trine; Jorgensen, Anne-Marie Klint

2018-01-01

Objectives: This review evaluates the evidence on the effects of cognitive-behavioral therapy (CBT) on drug use reduction for young people in treatment for nonopioid drug use. Method: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized trials. Meta-analytic methods were used to…

Cognitive-Behavioural Therapies for Young People in Outpatient Treatment for Non-Opioid Drug Use:

DEFF Research Database (Denmark)

Filges, Trine; Knudsen, Anne-Sofie Due; Svendsen, Majken

2015-01-01

), Multidimensional Family Therapy (MDFT), and Psychoeducational Therapy (PET)). RESULTS Our main objective was to evaluate the current evidence on the effect of CBT on abstinence and drug use reduction for young people in outpatient treatment for non-opioid drug use. Seven randomised trials, involving 953......, and PET ) with respect to reduction in young people’s drug use. The evidence drawn from this systematic review is based on seven included studies analysed in two separate analyses, depending on whether the intervention was CBT with an add-on component such as motivational interviewing (four studies......) or CBT without an add-on component (three studies). The seven studies are very different in terms of their findings regarding the effects of CBT interventions compared to other interventions (ACRA, CBOP (+ACC), DHPE, FFT, IT, MDFT, and PET ) on young people’s drug use. Therefore, the overall conclusion...

Preictal Dynamics of EEG Complexity in Intracranially Recorded Epileptic Seizure

Czech Academy of Sciences Publication Activity Database

Bob, P.; Roman, R.; Světlák, M.; Kukleta, M.; Chládek, Jan; Brázdil, M.

2014-01-01

Roč. 93, č. 23 (2014), el151:1-4 ISSN 0025-7974 R&D Projects: GA MŠk(CZ) LO1212 Institutional support: RVO:68081731 Keywords : EEG * epileptic Seizure Subject RIV: FS - Medical Facilities ; Equipment Impact factor: 5.723, year: 2014

Glial adenosine kinase--a neuropathological marker of the epileptic brain

NARCIS (Netherlands)

Aronica, Eleonora; Sandau, Ursula S.; Iyer, Anand; Boison, Detlev

2013-01-01

Experimental research over the past decade has supported the critical role of astrocytes activated by different types of injury and the pathophysiological processes that underlie the development of epilepsy. In both experimental and human epileptic tissues astrocytes undergo complex changes in their

Causes of mortality in early infantile epileptic encephalopathy: A systematic review.

Science.gov (United States)

Radaelli, Graciane; de Souza Santos, Francisco; Borelli, Wyllians Vendramini; Pisani, Leonardo; Nunes, Magda Lahorgue; Scorza, Fulvio Alexandre; da Costa, Jaderson Costa

2018-06-12

Early infantile epileptic encephalopathy syndrome (EIEE), also known as Ohtahara syndrome, is an age-dependent epileptic encephalopathy syndrome defined by clinical features and electroencephalographic findings. Epileptic disorders with refractory seizures beginning in the neonatal period and/or early infancy have a potential risk of premature mortality, including sudden death. We aimed to identify the causes of death in EIEE and conducted a literature survey of fatal outcomes. We performed a literature search in MEDLINE, EMBASE, and Web of Science for data from inception until September 2017. The terms "death sudden," "unexplained death," "SUDEP," "lethal," and "fatal" and the medical subject heading terms "epileptic encephalopathy," "mortality," "death," "sudden infant death syndrome," and "human" were used in the search strategy. The EIEE case report studies reporting mortality were included. The search yielded 1360 articles. After screening for titles and abstracts and removing duplicate entries, full texts of 15 articles were reviewed. After reading full texts, 11 articles met the inclusion criteria (9 articles in English and 2 in Japanese, dated from 1976 to 2015). The review comprised 38 unique cases of EIEE, 17 of which had death as an outcome. In all cases, the suppression-burst pattern on electroencephalographies (EEGs) was common. Most cases (55%) involved male infants. The mean (standard deviation [SD]) age at onset of seizure was 19.6 ± 33 days. The mean (SD) age at death was 12.9 ± 14.1 months. Most infants (58.8%) survived less than one year. The cause of death was described only in eight (47%) patients; the cause was pneumonia/respiratory illness or sudden unexpected death in epilepsy (SUDEP). The results show EIEE as a severe disease associated with a premature mortality, evidenced by a very young age at death. Increasing interest in the detection of new molecular bases of EIEE is leading us to a better understanding of this severe

Studies on long-lasting consequences of prenatal exposure to anticonvulsant drugs

NARCIS (Netherlands)

Dessens, A. B.; Boer, K.; Koppe, J. G.; van de Poll, N. E.; Cohen-Kettenis, P. T.

1994-01-01

Based on neonatal examination at birth, it has been estimated that epileptic women have a 2-3 times greater risk of giving birth to an infant with congenital anomalies. But anticonvulsant drugs may also have more subtle influences on the developing foetus which are not visible at birth but only

Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy: a novel strategy in drug development

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Jan eStenvang

2013-12-01

Full Text Available Cancer is a leading cause of mortality worldwide and matters are only set to worsen as its incidence continues to rise. Traditional approaches to combat cancer include improved prevention, early diagnosis, optimized surgery, development of novel drugs and honing regimens of existing anti-cancer drugs. Although discovery and development of novel and effective anti-cancer drugs is a major research area, it is well known that oncology drug development is a lengthy process, extremely costly and with high attrition rates. Furthermore, those drugs that do make it through the drug development mill are often quite expensive, laden with severe side-effects and, unfortunately, to date, have only demonstrated minimal increases in overall survival. Therefore, a strong interest has emerged to identify approved non-cancer drugs that possess anti-cancer activity, thus shortcutting the development process. This research strategy is commonly known as drug repurposing or drug repositioning and provides a faster path to the clinics. We have developed and implemented a modification of the standard drug repurposing strategy that we review here; rather than investigating target-promiscuous non-cancer drugs for possible anti-cancer activity, we focus on the discovery of novel cancer indications for already approved chemotherapeutic anti-cancer drugs. Clinical implementation of this strategy is normally commenced at clinical phase II trials and includes pre-treated patients. As the response rates to any non-standard chemotherapeutic drug will be relatively low in such a patient cohort it is a pre-requisite that such testing is based on predictive biomarkers. This review describes our strategy of biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy, taking the repurposing of topoisomerase I inhibitors and topoisomerase I as a potential predictive biomarker as case in point.

42 CFR 423.153 - Drug utilization management, quality assurance, and medication therapy management programs (MTMPs).

Science.gov (United States)

2010-10-01

... PRESCRIPTION DRUG BENEFIT Cost Control and Quality Improvement Requirements § 423.153 Drug utilization... 42 Public Health 3 2010-10-01 2010-10-01 false Drug utilization management, quality assurance, and medication therapy management programs (MTMPs). 423.153 Section 423.153 Public Health CENTERS FOR MEDICARE...

Mozart K.545 Mimics Mozart K.448 in Reducing Epileptiform Discharges in Epileptic Children

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Lung-Chang Lin

2012-01-01

Full Text Available Mozart K.448 has been shown to improve cognitive function, leading to what is known as the Mozart Effect. Our previous work reveals positive effects of Mozart K.448 in reducing epileptiform discharges in epileptic children. In this study, we evaluated the effect of Mozart K.545 and compared the effects with those of Mozart K.448 on epileptiform discharges in children with epilepsy. Thirty-nine epileptic children with epileptiform discharges were included in the study. They received electroencephalogram examinations before, during, and after listening to Mozart K.448 and K.545, one week apart, respectively. The frequencies of epileptiform discharges were compared. There was a significant decrease in the frequency of epileptiform discharges during and right after listening to Mozart K.448 and K.545 (reduced by 35.7±32.7% during Mozart K.448 and 30.3±44.4% after Mozart K.448; and 34.0±39.5% during Mozart K.545 and 31.8±39.2% after Mozart K.545. Spectrogrammatic analysis of the two pieces of music demonstrated that both share similar spectrogrammatic characteristics. Listening to Mozart K.448 and K.545 decreased the epileptiform discharges in epileptic children. This suggests that Mozart K.448 is not the only piece of music to have beneficial effects on children with epilepsy. Other music with lower harmonics may also decrease epileptiform discharges in epileptic children.

Magnetic chitosan nanoparticles as a drug delivery system for targeting photodynamic therapy

International Nuclear Information System (INIS)

Sun Yun; Chen Zhilong; Yang Xiaoxia; Huang Peng; Zhou Xinping; Du Xiaoxia

2009-01-01

Photodynamic therapy (PDT) has become an increasingly recognized alternative to cancer treatment in clinic. However, PDT therapy agents, namely photosensitizer (PS), are limited in application as a result of prolonged cutaneous photosensitivity, poor water solubility and inadequate selectivity, which are encountered by numerous chemical therapies. Magnetic chitosan nanoparticles provide excellent biocompatibility, biodegradability, non-toxicity and water solubility without compromising their magnetic targeting. Nevertheless, no previous attempt has been reported to develop an in vivo magnetic drug delivery system with chitosan nanoparticles for magnetic resonance imaging (MRI) monitored targeting photodynamic therapy. In this study, magnetic targeting chitosan nanoparticles (MTCNPs) were prepared and tailored as a drug delivery system and imaging agents for PS, designated as PHPP. Results showed that PHPP-MTCNPs could be used in MRI monitored targeting PDT with excellent targeting and imaging ability. Non-toxicity and high photodynamic efficacy on SW480 carcinoma cells both in vitro and in vivo were achieved with this method at the level of 0-100 μM. Notably, localization of nanoparticles in skin and hepatic tissue was significantly less than in tumor tissue, therefore photosensitivity and hepatotoxicity can be attenuated.

Effectiveness of cognitive behavioral stress management on depression and anxiety symptoms of patients with epilepsy and migraine

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Mohammad Dehghanifiroozabadi

2015-01-01

Conclusion: According to the results of this study, cognitive behavioral stress management was effective on the depression and anxiety of epileptic and migraine patients, and chronic disease has no effect on this effectiveness. This method can be used in combination with drug therapy.

Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy.

Science.gov (United States)

Palmer, Adam C; Sorger, Peter K

2017-12-14

Combination cancer therapies aim to improve the probability and magnitude of therapeutic responses and reduce the likelihood of acquired resistance in an individual patient. However, drugs are tested in clinical trials on genetically diverse patient populations. We show here that patient-to-patient variability and independent drug action are sufficient to explain the superiority of many FDA-approved drug combinations in the absence of drug synergy or additivity. This is also true for combinations tested in patient-derived tumor xenografts. In a combination exhibiting independent drug action, each patient benefits solely from the drug to which his or her tumor is most sensitive, with no added benefit from other drugs. Even when drug combinations exhibit additivity or synergy in pre-clinical models, patient-to-patient variability and low cross-resistance make independent action the dominant mechanism in clinical populations. This insight represents a different way to interpret trial data and a different way to design combination therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

Nanotechnology-Based Drug Delivery Systems for Melanoma Antitumoral Therapy: A Review.

Science.gov (United States)

Rigon, Roberta Balansin; Oyafuso, Márcia Helena; Fujimura, Andressa Terumi; Gonçalez, Maíra Lima; do Prado, Alice Haddad; Gremião, Maria Palmira Daflon; Chorilli, Marlus

2015-01-01

Melanoma (MEL) is a less common type of skin cancer, but it is more aggressive with a high mortality rate. The World Cancer Research Fund International (GLOBOCAN 2012) estimates that there were 230,000 new cases of MEL in the world in 2012. Conventional MEL treatment includes surgery and chemotherapy, but many of the chemotherapeutic agents used present undesirable properties. Drug delivery systems are an alternative strategy by which to carry antineoplastic agents. Encapsulated drugs are advantageous due to such properties as high stability, better bioavailability, controlled drug release, a long blood circulation time, selective organ or tissue distribution, a lower total required dose, and minimal toxic side effects. This review of scientific research supports applying a nanotechnology-based drug delivery system for MEL therapy.

Analysis of combination drug therapy to develop regimens with shortened duration of treatment for tuberculosis.

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George L Drusano

Full Text Available Tuberculosis remains a worldwide problem, particularly with the advent of multi-drug resistance. Shortening therapy duration for Mycobacterium tuberculosis is a major goal, requiring generation of optimal kill rate and resistance-suppression. Combination therapy is required to attain the goal of shorter therapy.Our objective was to identify a method for identifying optimal combination chemotherapy. We developed a mathematical model for attaining this end. This is accomplished by identifying drug effect interaction (synergy, additivity, antagonism for susceptible organisms and subpopulations resistant to each drug in the combination.We studied the combination of linezolid plus rifampin in our hollow fiber infection model. We generated a fully parametric drug effect interaction mathematical model. The results were subjected to Monte Carlo simulation to extend the findings to a population of patients by accounting for between-patient variability in drug pharmacokinetics.All monotherapy allowed emergence of resistance over the first two weeks of the experiment. In combination, the interaction was additive for each population (susceptible and resistant. For a 600 mg/600 mg daily regimen of linezolid plus rifampin, we demonstrated that >50% of simulated subjects had eradicated the susceptible population by day 27 with the remaining organisms resistant to one or the other drug. Only 4% of patients had complete organism eradication by experiment end.These data strongly suggest that in order to achieve the goal of shortening therapy, the original regimen may need to be changed at one month to a regimen of two completely new agents with resistance mechanisms independent of the initial regimen. This hypothesis which arose from the analysis is immediately testable in a clinical trial.

Radioiodine therapy and thyrostatic drugs and iodine

Energy Technology Data Exchange (ETDEWEB)

Moka, D.; Dietlein, M.; Schicha, H. [Department of Nuclear Medicine, University of Cologne, Joseph Stelzmannstrasse 9, 50924 Koeln (Germany)

2002-08-01

Radioiodine therapy is now the most common definite treatment for persistent hyperthyroidism. The outcome of radioiodine therapy depends mainly on the absorbed energy dose in the diseased thyroid tissue. The administered activity and the resulting target dose in the thyroid depend on both the biokinetics of radioiodine and the actual therapeutic effect of radioiodine in the thyroid. Thyrostatic drugs have a major influence on the kinetics of radioiodine in the thyroid and may additionally have a radioprotective effect. Pre-treatment with thyrostatic medication lowers the effective half-life and uptake of radioiodine. This can reduce the target dose in the thyroid and have a negative influence on the outcome of the therapy. Discontinuation of medication shortly before radioiodine administration can increase the absorbed energy dose in the thyroid without increasing the whole-body exposure to radiation as much as would a higher or second radioiodine administration. Furthermore, administration of non-radioactive iodine-127 2-3 days after radioiodine administration can also increase the effective half-life of radioiodine in the thyroid. Thus, improving the biokinetics of radioiodine will allow lower activities to be administered with lower effective doses to the rest of the body, while achieving an equally effective target dose in the thyroid. (orig.)

Management of noninfectious posterior uveitis with intravitreal drug therapy

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Tan HY

2016-10-01

Full Text Available Hui Yi Tan,1 Aniruddha Agarwal,2 Cecilia S Lee,3 Jay Chhablani,4 Vishali Gupta,5 Manoj Khatri,6 Jayabalan Nirmal,7 Carlos Pavesio,8 Rupesh Agrawal1,7–9 1Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 2Department of Vitreoretina, Stanley M Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, 3Department of Ophthalmology, University of Washington, Seattle, WA, USA; 4Department of Vitreoretina, L V Prasad Eye Institute, Hyderabad, Telangana, 5Department of Retina and Uvea, Post Graduate Institute of Medical Education and Research, Chandigarh, 6Department of Retina, Rajan Eye Care Hospital, Chennai, Tamil Nadu, India; 7School of Material Science and Engineering, Nanyang Technological University, Singapore; 8Department of Medical Retina, Moorfields Eye Hospital, NHS Foundation Trust, London, UK; 9Department of Ophthalmology, National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore Abstract: Uveitis is an important cause of vision loss worldwide due to its sight-threatening complications, especially cystoid macular edema, as well as choroidal neovascularization, macular ischemia, cataract, and glaucoma. Systemic corticosteroids are the mainstay of therapy for noninfectious posterior uveitis; however, various systemic side effects can occur. Intravitreal medication achieves a therapeutic level in the vitreous while minimizing systemic complications and is thus used as an exciting alternative. Corticosteroids, antivascular endothelial growth factors, immunomodulators such as methotrexate and sirolimus, and nonsteroidal anti-inflammatory drugs are currently available for intravitreal therapy. This article reviews the existing literature for efficacy and safety of these various options for intravitreal drug therapy for the management of noninfectious uveitis (mainly intermediate, posterior, and panuveitis. Keywords: intravitreal therapy, noninfectious uveitis, posterior uveitis

Fighting cancer with nanomedicine---drug-polyester nanoconjugates for targeted cancer therapy

Science.gov (United States)

Yin, Qian

The aim of my Ph. D. research is to develop drug-polyester nanoconjugates (NCs) as a novel translational polymeric drug delivery system that can successfully evade non-specific uptake by reticuloendothelial system (RES) and facilitate targeted cancer diagnosis and therapy. By uniquely integrating well-established chemical reaction-controlled ring opening polymerization (ROP) with nanoprecipitation technique, I successfully developed a polymeric NC system based on poly(lactic acid) and poly(O-carboxyanhydrides) (OCA) that allows for the quantitative loading and controlled release of a variety of anticancer drugs. The developed NC system could be easily modified with parmidronate, one of bisphosphonates commonly used as the treatment for disease characterized by osteolysis, to selectively deliver doxorubicin (Doxo) to the bone tissues and substantially to improve their therapeutic efficiency in inhibiting the growth of osteosarcoma in both murine and canine models. More importantly, the developed NCs could avidly bind to human serum albumin, a ubiquitous protein in the blood, to bypass the endothelium barrier and penetrate into tumor tissues more deeply and efficiently. When compared with PEGylated NCs, these albumin-bound NCs showed significantly reduced accumulation in RES and enhanced tumor accumulation, which consequently contributed to higher their tumor inhibition capabilities. In addition, the developed NC system allows easy incorporation of X-ray computed tomography (CT) contrast agents to largely facilitate personalized therapy by improving diagnosis accuracy and monitoring therapeutic efficacy. Through the synthetic and formulation strategy I developed, a large quantity (grams or larger-scale) of drug-polyester NCs can be easily obtained, which can be used as a model drug delivery system for fundamental studies as well as a real drug delivery system for disease treatment in clinical settings.

Predicting epileptic seizures in advance.

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Negin Moghim

Full Text Available Epilepsy is the second most common neurological disorder, affecting 0.6-0.8% of the world's population. In this neurological disorder, abnormal activity of the brain causes seizures, the nature of which tend to be sudden. Antiepileptic Drugs (AEDs are used as long-term therapeutic solutions that control the condition. Of those treated with AEDs, 35% become resistant to medication. The unpredictable nature of seizures poses risks for the individual with epilepsy. It is clearly desirable to find more effective ways of preventing seizures for such patients. The automatic detection of oncoming seizures, before their actual onset, can facilitate timely intervention and hence minimize these risks. In addition, advance prediction of seizures can enrich our understanding of the epileptic brain. In this study, drawing on the body of work behind automatic seizure detection and prediction from digitised Invasive Electroencephalography (EEG data, a prediction algorithm, ASPPR (Advance Seizure Prediction via Pre-ictal Relabeling, is described. ASPPR facilitates the learning of predictive models targeted at recognizing patterns in EEG activity that are in a specific time window in advance of a seizure. It then exploits advanced machine learning coupled with the design and selection of appropriate features from EEG signals. Results, from evaluating ASPPR independently on 21 different patients, suggest that seizures for many patients can be predicted up to 20 minutes in advance of their onset. Compared to benchmark performance represented by a mean S1-Score (harmonic mean of Sensitivity and Specificity of 90.6% for predicting seizure onset between 0 and 5 minutes in advance, ASPPR achieves mean S1-Scores of: 96.30% for prediction between 1 and 6 minutes in advance, 96.13% for prediction between 8 and 13 minutes in advance, 94.5% for prediction between 14 and 19 minutes in advance, and 94.2% for prediction between 20 and 25 minutes in advance.

Cognitive-Behavioural Therapies for Young People in Outpatient Treatment for NonOpioid Drug Use

DEFF Research Database (Denmark)

Filges, Trine; Jørgensen, Anne-Marie Klint

2016-01-01

Objectives: This review evaluates the evidence on the effects of cognitive–behavioral therapy (CBT) on drug use reduction for young people in treatment for nonopioid drug use. Method: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized trials...

Drug utilization pattern in a pain clinic of a tertiary care teaching hospital in Eastern India

Directory of Open Access Journals (Sweden)

Debjyoti Dutta

2013-01-01

Full Text Available Background: Patients attend the Pain Clinic with varieties of complains of pain, like low back pain, knee pain, shoulder pain, headache, facial pain, different neuralgias and other neuropathic pain states. They receive a multimodal treatment for their pain, Multimodal pain therapy is an integrated multidisciplinary treatment in small groups with a closely coordinated therapeutic approach. Drugs that are prescribed for treatment are not only NSAIDS or Opioids, but also various groups of adjuvant pain medications like anti-epileptics, antidepressants etc. Aim: To find out the drug utilization pattern in the Pain Clinic of a tertiary care medical college hospital in Eastern India. Materials and Methods: A cross sectional; unicentric study was conducted in the Pain Clinic during April 2013 to June 2013. New patients who were willing to participate in the study were enrolled as per selection criteria. A copy of prescriptions were collected from the patients. The drugs prescription patterns were analyzed. Result: 319 patients were included in this study in three months period and their prescriptions were analyzed. Female patients (222 were more in number than male (97. As single prescription and also as combination therapy, paracetamol was found to be the most frequently prescribed drug. Frequently used adjuvant pain medications were found to be pregabalin (21.63% and amitriptyline (16.92%.. Antacid was commonly prescribed as gastroprotective agent. Among drug combinations paracetamol (325 mg + tramadol (37.5 mg combination was used most frequently. (55.17%. Conclusion: In this uncentric study we found that patacetamol, tramadol, pregabalin and amitriptyline are the commonly used medications in a pain clinic. We need more multi-centric and comparative Indian studies.

Hidden pattern discovery on epileptic EEG with 1-D local binary patterns and epileptic seizures detection by grey relational analysis.

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Kaya, Yılmaz

2015-09-01

This paper proposes a novel approach to detect epilepsy seizures by using Electroencephalography (EEG), which is one of the most common methods for the diagnosis of epilepsy, based on 1-Dimension Local Binary Pattern (1D-LBP) and grey relational analysis (GRA) methods. The main aim of this paper is to evaluate and validate a novel approach, which is a computer-based quantitative EEG analyzing method and based on grey systems, aimed to help decision-maker. In this study, 1D-LBP, which utilizes all data points, was employed for extracting features in raw EEG signals, Fisher score (FS) was employed to select the representative features, which can also be determined as hidden patterns. Additionally, GRA is performed to classify EEG signals through these Fisher scored features. The experimental results of the proposed approach, which was employed in a public dataset for validation, showed that it has a high accuracy in identifying epileptic EEG signals. For various combinations of epileptic EEG, such as A-E, B-E, C-E, D-E, and A-D clusters, 100, 96, 100, 99.00 and 100% were achieved, respectively. Also, this work presents an attempt to develop a new general-purpose hidden pattern determination scheme, which can be utilized for different categories of time-varying signals.

Functional Family Therapy for Young People in Treatment for Nonopioid Drug Use

DEFF Research Database (Denmark)

Filges, Trine; Andersen, Ditte

2016-01-01

Objectives: This review evaluates the evidence on the effects of functional family therapy (FFT) on drug abuse reduction for young people in treatment for nonopioid drug use. Data and Analysis: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized...... and nonrandomized trials. Results: The search yielded two studies that met inclusion criteria. Only one study provided numerical results on the effect of FFT on drug use reduction. Conclusions: There is insufficient evidence to allow any conclusion to be drawn on the effect of FFT for young people in treatment...

Brief strategic family therapy for young people in treatment for drug use

DEFF Research Database (Denmark)

Lindstrøm, Maia; Filges, Trine; Jørgensen, Anne-Marie Klint

2015-01-01

This review evaluates the evidence on the effects of brief strategic family therapy (BSFT) on drug use reduction for young people in treatment for nonopioid drug use. Method: We followed Campbell Collaboration guidelines to prepare this review and ultimately located three studies for final analysis...... and interpretation. Results: The results are mixed: BSFT does not seem to have better or worse effects on drug use frequency and family functioning than other treatments but has positive effects on treatment retention compared to control conditions. Longer retention in treatment has been identified as a consistent...

Epileptic seizure detection from EEG signals with phase-amplitude cross-frequency coupling and support vector machine

Science.gov (United States)

Liu, Yang; Wang, Jiang; Cai, Lihui; Chen, Yingyuan; Qin, Yingmei

2018-03-01

As a pattern of cross-frequency coupling (CFC), phase-amplitude coupling (PAC) depicts the interaction between the phase and amplitude of distinct frequency bands from the same signal, and has been proved to be closely related to the brain’s cognitive and memory activities. This work utilized PAC and support vector machine (SVM) classifier to identify the epileptic seizures from electroencephalogram (EEG) data. The entropy-based modulation index (MI) matrixes are used to express the strength of PAC, from which we extracted features as the input for classifier. Based on the Bonn database, which contains five datasets of EEG segments obtained from healthy volunteers and epileptic subjects, a 100% classification accuracy is achieved for identifying seizure ictal from healthy data, and an accuracy of 97.67% is reached in the classification of ictal EEG signals from inter-ictal EEGs. Based on the CHB-MIT database which is a group of continuously recorded epileptic EEGs by scalp electrodes, a 97.50% classification accuracy is obtained and a raising sign of MI value is found at 6s before seizure onset. The classification performance in this work is effective, and PAC can be considered as a useful tool for detecting and predicting the epileptic seizures and providing reference for clinical diagnosis.

Danish epileptics given Thorotrast

International Nuclear Information System (INIS)

Olsen, J.H.; Anderson, M.; Boice, J.D. Jr.

1989-01-01

Cancer incidence among 8004 patients hospitalized for epilepsy between 1933 and 1962 was compared to that of the general population. Among 140 epileptics given Thorotrast during cerebral angiography, a significant excess of cancer was observed. Thorotrast exposure was linked to significant excesses of liver cancer, leukaemia and lung cancer. An excess of brain cancer occurred shortly after hospital admission, suggesting brain tumours were the cause of the seizure disorder and are not due to Thorotrast. Haemangiosarcomas of the liver appeared uniquely related to Thorotrast, as did the rare subtypes of leukaemia observed. Cholangiocarcinomas also occurred in excess. The preponderance of anaplastic lung cancer is provocative and suggests the possibility that thoron exposure from the decay of Thorotrast might be involved. The cumulative risk of developing cancer at 40 years, excluding the brain cancer risk, was 60±6%. (author)

Cognitive-Behavioral Treatment of Depressed Affect among Epileptics: Preliminary Findings.

Science.gov (United States)

Davis, Gay R.; And Others

1984-01-01

Evaluated a program where cognitive-behavioral methods were utilized in a structured learning format with clinically depressed epileptics (N=13). Results indicated that cognitive behavioral interventions result in significant decreases in depression and increases in related areas of psychosocial functioning that are maintained over time. (LLL)

Computer-aided diagnosis of interictal 18F-FDG PET images for presurgical evaluation of epileptic foci in extratemporal lobe epilepsy

International Nuclear Information System (INIS)

Imabayashi, Etsuko

2003-01-01

Interictal 18 F-FDG PET is beneficial to patients with epilepsy to define the epileptic foci before operation, especially to decide the laterality of temporal lobe epilepsy (TLE). However usefulness has not been clearly established in extra TLE. We retrospectively applied Z-score analysis to interictal preoperative 18 F-FDG PET images for detection of the epileptic foci in order to achieve better performance. Seventeen epileptic patients (women/men; 8/9, age; 11-55 yrs) underwent resection of epileptic foci with good outcome (Engel's stage of I or II) even after more than a year from operation. Presurgical 18 F-FDG PET images were spatially normalized using statistical parametric mapping 99 (SPM99) with an original Japanese template for 18 F-FDG and compared with normal database constructed from 31 healthy volunteers (women/men; 14/17, age; 19-59 yrs). A software program, easy Z-score imaging system (eZIS), for analysis of patient data was developed by calculating Z-score in each voxel and visualizing the score in a standardized stereotactic space; Z-score=(normal mean-patient's value)/a standard deviation of normal data. Detectability of epileptic foci for this computer-aided analysis was compared with visual inspection of original 18 F-FDG PET images by five radiologists without any clinical information. In all cases, there was significant reduction of glucose metabolism in the operated area. The sensitivities of the detection of epileptic foci obtained from visual inspection were 47-59%. In contrast to, computer analysis by eZIS showed 71% sensitivity when we defined the highest Z-score in the cerebrum to be the focus diagnosed by eZIS. Computer-aided diagnosis with eZIS for 18 F-FDG PET study is useful for detecting epileptic foci in extra TLE. (author)

Effect of impaired ambulation and anti-epileptic drug intake on vitamin D status of children with cerebral palsy.

Science.gov (United States)

Seth, Anju; Aneja, Satinder; Singh, Ritu; Majumdar, Ritu; Sharma, Neera; Gopinath, Muthuselvan

2017-08-01

Children with cerebral palsy (CP) are vulnerable to developing vitamin D deficiency. There is little information on the prevalence and severity of vitamin D deficiency in these patients. To study vitamin D status in children with CP with special reference to their intake of anti-epileptic drugs (AED) and ambulatory status. The relative effects of AED use and ambulatory status on the vitamin D status of 120 children with CP aged 2-10 years were examined in this observational study. The patients were classified into four groups (30 in each) on the basis of AED use and ambulatory status: ambulatory (CPA), ambulatory receiving AED (CPAD), non-ambulatory (CPNA) and non-ambulatory receiving AED (CPNAD). A control group of 30 age-matched healthy children was also included. Parameters assessed included dietary calcium intake, sun exposure, serum total and ionised calcium (tCa, iCa), inorganic phosphate (iP), alkaline phosphatase (ALP), parathormone (PTH), 25 hydroxy vitamin D [25(OH)D] levels and a wrist radiograph to detect rickets. Vitamin D status was defined on the basis of serum 25(OH)D levels as normal (>50 nmol/L), mild deficiency (25-50 nmol/L), moderate deficiency (12.5-25 nmol/L), severe deficiency (D levels in patients with CP were 35.6 (26.75-64) nmol/L compared with 60 (37-69.25) nmol/L in controls (p = 0.04). Sixty per cent of children with CP and 36.7% of controls were vitamin D-deficient [25(OH)D D-deficient with median (IQR) 25(OH)D levels of 33.5 (12.5-45.25) nmol/L. Also, 53.3% of them had raised ALP and 17.2% raised PTH levels. Children with CP are highly vulnerable to vitamin D deficiency. In these patients, AED use and lack of sun exposure contribute towards poor vitamin D status, the effect being more pronounced when they co-exist.

Ictal brain SPET during seizures pharmacologically provoked with pentylenetetrazol: a new diagnostic procedure in drug-resistant epileptic patients

International Nuclear Information System (INIS)

Calcagni, Maria Lucia; Giordano, Alessandro; Bruno, Isabella; Di Giuda, Daniela; De Rossi, Giuseppe; Troncone, Luigi; Parbonetti, Giovanni; Colicchio, Gabriella

2002-01-01

Functional brain imaging plays an important role in seizure focus localisation. However, truly ictal single-photon emission tomography (SPET) studies are not routinely performed owing to technical problems associated with the use of tracers and methodological and logistical difficulties. In this study we tried to resolve both of these issues by means of a new procedure: technetium-99m ethyl cysteinate dimer (ECD) brain SPET performed during seizures pharmacologically provoked with pentylenetetrazol, a well-known central and respiratory stimulant. We studied 33 drug-resistant epileptic patients. All patients underwent anamnestic evaluation, neuropsychological and psychodynamic assessment, magnetic resonance imaging, interictal and ictal video-EEG monitoring, and interictal and ictal SPET with 99m Tc-ECD. In order to obtain truly ictal SPET, 65 mg of pentylenetetrazol was injected every 2 minutes and, immediately the seizure began, 740 MBq of 99m Tc-ECD was injected. The scintigraphic findings were considered abnormal if a single area of hyperperfusion was present and corresponded to the site of a single area of hypoperfusion at interictal SPET: the ''hypo-hyperperfusion'' SPET pattern. In 27 of the 33 patients (82%), interictal-ictal SPET showed the hypo-hyperperfusion SPET pattern. Video-EEG showed a single epileptogenic zone in 21/33 patients (64%), and MRI showed anatomical lesions in 19/33 patients (57%). Twenty-two of the 27 patients with hypo-hyperperfusion SPET pattern underwent ablative or palliative surgery and were seizure-free at 3 years of follow-up. No adverse effects were noted during pharmacologically provoked seizure. It is concluded that ictal brain SPET performed during pharmacologically provoked seizure provides truly ictal images because 99m Tc-ECD is injected immediately upon seizure onset. Using this feasible procedure it is possible to localise the focus, to avoid the limitations due to the unpredictability of seizures, to avoid pitfalls due

Achieving a Spiritual Therapy Standard for Drug Dependency in Malaysia, from an Islamic Perspective: Brief Review Article.

Science.gov (United States)

Seghatoleslam, Tahereh; Habil, Hussain; Hatim, Ahmad; Rashid, Rusdi; Ardakan, Abolfazl; Esmaeili Motlaq, Farid

2015-01-01

Religion is one of the protective factors that facilities positive outcomes by preventing individuals from engaging in addictive substance. A recent study has confirmed that religion inhibits drug addiction. The concept of psychospiritual therapy was to introduce drug addiction. Therefore, of the various methods of psychotherapy, the usage of Taqwa (piety) emerged as an applicable method of Islamic spiritual therapy. This study was conducted in Malaysia as a Muslim country and focuses on Islamic recommendations and its relation to spiritual therapy.

帕金森病的药物治疗%Drug therapy for Parkinson's disease

Institute of Scientific and Technical Information of China (English)

杨任民

2011-01-01

帕金森病(PD)的多种治疗药物是针对运动症状的治疗,而PD非运动症状可降低患者生活质量,甚至可加重PD患者的运动症状和功能残疾,其治疗也不容忽视.本文综述PD运动症状的药物治疗原则,以及各类药物的临床使用及其疗效评价,同时汇总多种非运动症状的药物治疗研究.%Several drugs have been used to treat the motor symptoms of Parkinson's disease (PD). Non-motor symptoms may reduce quality of life, cause more motor symptoms and functional disability in PD patients. The therapy for non-motor symptoms should not be ignored. This review describes the principle and application of drug therapy for motor symptoms of PD, and summarizes drug therapy for a variety of non-motor symptoms.

Characteristics of Hemorrhagic Peptic Ulcers in Patients Receiving Antithrombotic/Nonsteroidal Antiinflammatory Drug Therapy

OpenAIRE

Nakamura, Kazuhiko; Akahoshi, Kazuya; Ochiai, Toshiaki; Komori, Keishi; Haraguchi, Kazuhiro; Tanaka, Munehiro; Nakamura, Norimoto; Tanaka, Yoshimasa; Kakigao, Kana; Ogino, Haruei; Ihara, Eikichi; Akiho, Hirotada; Motomura, Yasuaki; Kabemura, Teppei; Harada, Naohiko

2012-01-01

Background/Aims Antithrombotic/nonsteroidal antiinflammatory drug (NSAID) therapies increase the incidence of upper gastrointestinal bleeding. The features of hemorrhagic peptic ulcer disease in patients receiving antithrombotic/NSAID therapies were investigated. Methods We investigated the medical records of 485 consecutive patients who underwent esophagogastroduodenoscopy and were diagnosed with hemorrhagic gastroduodenal ulcers. The patients treated with antithrombotic agents/NSAIDs were c...

Chinese herbal therapy and Western drug use, belief and adherence for hypertension management in the rural areas of Heilongjiang province, China.

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Xia Li

Full Text Available Traditional Chinese medicine (TCM including Chinese herbal therapy has been widely practiced in China. However, little is known about Chinese herbal therapy use for hypertension management, which is one of the most prevalent chronic conditions in China. Thus we described Chinese herbal therapy and western drug users, beliefs, hypertension knowledge, and Chinese herbal and western drug adherence and determinants of Chinese herbal therapy use among patients with hypertension in rural areas of Heilongjiang Province, China.This face-to-face cross sectional survey included 665 hypertensive respondents aged 30 years or older in rural areas of Heilongjiang Province, China. Of 665 respondents, 39.7% were male, 27.4% were aged 65 years or older. At the survey, 14.0% reported using Chinese herbal therapy and 71.3% reported using western drug for hypertension management. A majority of patients had low level of treatment adherence (80.6% for the Chinese herbal therapy users and 81.2% for the western drug users. When respondents felt that their blood pressure was under control, 72.0% of the Chinese herbal therapy users and 69.2% of the western drug users sometimes stopped taking their medicine. Hypertensive patients with high education level or better quality of life are more likely use Chinese herbal therapy.Majority of patients diagnosed with hypertension use western drugs to control blood pressure. Chinese herbal therapy use was associated with education level and quality of life.

Nanoparticle-Based Drug Delivery for Therapy of Lung Cancer: Progress and Challenges

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Anish Babu

2013-01-01

Full Text Available The last decade has witnessed enormous advances in the development and application of nanotechnology in cancer detection, diagnosis, and therapy culminating in the development of the nascent field of “cancer nanomedicine.” A nanoparticle as per the National Institutes of Health (NIH guidelines is any material that is used in the formulation of a drug resulting in a final product smaller than 1 micron in size. Nanoparticle-based therapeutic systems have gained immense popularity due to their ability to overcome biological barriers, effectively deliver hydrophobic therapies, and preferentially target disease sites. Currently, many formulations of nanocarriers are utilized including lipid-based, polymeric and branched polymeric, metal-based, magnetic, and mesoporous silica. Innovative strategies have been employed to exploit the multicomponent, three-dimensional constructs imparting multifunctional capabilities. Engineering such designs allows simultaneous drug delivery of chemotherapeutics and anticancer gene therapies to site-specific targets. In lung cancer, nanoparticle-based therapeutics is paving the way in the diagnosis, imaging, screening, and treatment of primary and metastatic tumors. However, translating such advances from the bench to the bedside has been severely hampered by challenges encountered in the areas of pharmacology, toxicology, immunology, large-scale manufacturing, and regulatory issues. This review summarizes current progress and challenges in nanoparticle-based drug delivery systems, citing recent examples targeted at lung cancer treatment.

Population-based differences in treatment outcome following anticancer drug therapies.

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Ma, Brigette By; Hui, Edwin P; Mok, Tony Sk

2010-01-01

Population-based differences in toxicity and clinical outcome following treatment with anticancer drugs have an important effect on oncology practice and drug development. These differences arise from complex interactions between biological and environmental factors, which include genetic diversity affecting drug metabolism and the expression of drug targets, variations in tumour biology and host physiology, socioeconomic disparities, and regional preferences in treatment standards. Some well-known examples include the high prevalence of activating epidermal growth factor receptor (EGFR) mutations in pulmonary adenocarcinoma among northeast (China, Japan, Korea) and parts of southeast Asia (excluding India) non-smokers, which predict sensitivity to EGFR kinase inhibitors, and the sharp contrast between Japan and the west in the management and survival outcome of gastric cancer. This review is a critical overview of population-based differences in the four most prevalent cancers in the world: lung, breast, colorectal, and stomach cancer. Particular attention is given to the clinical relevance of such knowledge in terms of the individualisation of drug therapy and in the design of clinical trials. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy

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Han-Chung Wu

2010-01-01

Full Text Available Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

Mouse neuroblastoma cell-based model and the effect of epileptic events on calcium oscillations and neural spikes

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Kim, Suhwan; Jung, Unsang; Baek, Juyoung; Lee, Sangwon; Jung, Woonggyu; Kim, Jeehyun; Kang, Shinwon

2013-01-01

Recently, mouse neuroblastoma cells have been considered as an attractive model for the study of human neurological and prion diseases, and they have been intensively used as a model system in different areas. For example, the differentiation of neuro2a (N2A) cells, receptor-mediated ion current, and glutamate-induced physiological responses have been actively investigated with these cells. These mouse neuroblastoma N2A cells are of interest because they grow faster than other cells of neural origin and have a number of other advantages. The calcium oscillations and neural spikes of mouse neuroblastoma N2A cells in epileptic conditions are evaluated. Based on our observations of neural spikes in these cells with our proposed imaging modality, we reported that they can be an important model in epileptic activity studies. We concluded that mouse neuroblastoma N2A cells produce epileptic spikes in vitro in the same way as those produced by neurons or astrocytes. This evidence suggests that increased levels of neurotransmitter release due to the enhancement of free calcium from 4-aminopyridine causes the mouse neuroblastoma N2A cells to produce epileptic spikes and calcium oscillations.

If the Airway Opens with Finger During Epileptics Attack: A Case Report

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Seyran Kilinc

2016-01-01

Full Text Available The human bites generally have been came across after the situation as fighting, aggression, murder, sports competitions and child abuse. Hands and wrists are the most common areas that human bites have seen. Our case was seen first time when 65 aged woman treating for diabetes mellitus in our endocrinology service consultated us with a neglected open wound that occurred after she put on her hands second finger%u2019s proximal phalanx to her relative%u2019s mouth to keep open duration of epileptic attack before 45 days. In this case we try to explain that the wrong intervention in epileptic attack and delaying treatment of infections of human bites can be resulted with limb missing.

Treatment of hyperthyroidism with radioiodine: adjunctive therapy with antithyroid drugs reconsidered

International Nuclear Information System (INIS)

Velkeniers, B.; Vanhaelst, L.; Cytryn, R.; Jonckheer, M.H.

1988-01-01

To assess the value of antithyroid drugs as an adjunct to radioactive iodine for the treatment of hyperthyroidism the incidence of relapse or hypothyroidism after a mean follow-up of 51/2 years (range 2-7 years) was reviewed retrospectively for 206 patients, some treated with and others without antithyroid drugs after radioiodine therapy. Allocation to treatment group had been random, and both groups were similar in all respects except for the adjunctive treatment with antithyroid drugs. All doses of 131 I had been calculated by one physician. Compared with those who received 131 I alone, those starting on antithyroid drugs within 8 days after 131 I had a lower incidence of hypothyroidism but a higher incidence of early post-treatment recurrence or persistence of hyperthyroidism, and considerably lower incidence of remission. (author)

Epileptic seizures in Neuro-Behcet disease: why some patients develop seizure and others not?

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Kutlu, Gulnihal; Semercioglu, Sencer; Ucler, Serap; Erdal, Abidin; Inan, Levent E

2015-03-01

Behcet disease (BD) is a chronic relapsing inflammatory disorder. Neuro BD (NBD) is seen in approximately 5% of all patients. The aim of this study is to investigate the frequency, type and prognosis of epileptic seizures in different forms of NBD. All files of 42 patients with NBD were evaluated between 2006 and 2012, retrospectively. The demographic data, the presentation of NBD, clinical findings including seizures, EEG and neuroimaging findings were reviewed. The mean age of patients was 35.02±8.43 years. Thirty (71.4%) patients were male; the remaining 12 of them were female. Twenty-four patients had brainstem lesions; 16 patients had cerebral venous thrombosis. Spinal cord involvement was seen in two patients. Seven patients had epileptic seizures (six partial onset seizures with or without secondary generalization). Six of them had cerebral sinus thrombosis (CVT). Four patients had a seizure as the first symptom of the thrombosis. One patient had late onset seizure due to chronic venous infarct. The other patient with seizure had brainstem involvement. The remaining was diagnosed as epilepsy before the determination of NBD. CVT seen in BD seems to be the main risk factor for epileptic seizures in patients with NBD. The prognosis is usually good especially in patients with CVT. Epileptic seizures in patients with brainstem involvement may be an indicator for poor prognosis. Superior sagittal thrombosis or cortical infarct would be predictor of seizures occurrence because of the high ratio in patients with seizures. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Nanotechnology-based drug delivery treatments and specific targeting therapy for age-related macular degeneration

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Tai-Chi Lin

2015-11-01

Full Text Available Nanoparticles combined with cells, drugs, and specially designed genes provide improved therapeutic efficacy in studies and clinical setting, demonstrating a new era of treatment strategy, especially in retinal diseases. Nanotechnology-based drugs can provide an essential platform for sustaining, releasing and a specific targeting design to treat retinal diseases. Poly-lactic-co-glycolic acid is the most widely used biocompatible and biodegradable polymer approved by the Food and Drug Administration. Many studies have attempted to develop special devices for delivering small-molecule drugs, proteins, and other macromolecules consistently and slowly. In this article, we first review current progress in the treatment of age-related macular degeneration. Then, we discuss the function of vascular endothelial growth factor (VEGF and the pharmacological effects of anti-VEGF-A antibodies and soluble or modified VEGF receptors. Lastly, we summarize the combination of antiangiogenic therapy and nanomedicines, and review current potential targeting therapy in age-related macular degeneration.

Astrocyte Senescence and Metabolic Changes in Response to HIV Antiretroviral Therapy Drugs

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Justin Cohen

2017-08-01

Full Text Available With the advent of highly active antiretroviral therapy (HAART survival rates among patients infected by HIV have increased. However, even though survival has increased HIV-associated neurocognitive disorders (HAND still persist, suggesting that HAART-drugs may play a role in the neurocognitive impairment observed in HIV-infected patients. Given previous data demonstrating that astrocyte senescence plays a role in neurocognitive disorders such as Alzheimer’s disease (AD, we examined the role of HAART on markers of senescence in primary cultures of human astrocytes (HAs. Our results indicate HAART treatment induces cell cycle arrest, senescence-associated beta-galactosidase, and the cell cycle inhibitor p21. Highly active antiretroviral therapy treatment is also associated with the induction of reactive oxygen species and upregulation of mitochondrial oxygen consumption. These changes in mitochondria correlate with increased glycolysis in HAART drug treated astrocytes. Taken together these results indicate that HAART drugs induce the senescence program in HAs, which is associated with oxidative and metabolic changes that could play a role in the development of HAND.

Transfer function between EEG and BOLD signals of epileptic activity

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Marco eLeite

2013-01-01

Full Text Available Simultaneous EEG-fMRI recordings have seen growing application in the evaluation of epilepsy, namely in the characterization of brain networks related to epileptic activity. In EEG-correlated fMRI studies, epileptic events are usually described as boxcar signals based on the timing information retrieved from the EEG, and subsequently convolved with a heamodynamic response function to model the associated BOLD changes. Although more flexible approaches may allow a higher degree of complexity for the haemodynamics, the issue of how to model these dynamics based on the EEG remains an open question. In this work, a new methodology for the integration of simultaneous EEG-fMRI data in epilepsy is proposed, which incorporates a transfer function from the EEG to the BOLD signal. Independent component analysis (ICA of the EEG is performed, and a number of metrics expressing different models of the EEG-BOLD transfer function are extracted from the resulting time courses. These metrics are then used to predict the fMRI data and to identify brain areas associated with the EEG epileptic activity. The methodology was tested on both ictal and interictal EEG-fMRI recordings from one patient with a hypothalamic hamartoma. When compared to the conventional analysis approach, plausible, consistent and more significant activations were obtained. Importantly, frequency-weighted EEG metrics yielded superior results than those weighted solely on the EEG power, which comes in agreement with previous literature. Reproducibility, specificity and sensitivity should be addressed in an extended group of patients in order to further validate the proposed methodology and generalize the presented proof of concept.

Pharmacological analysis of postictal refractoriness after cortical epileptic seizures in rats

Czech Academy of Sciences Publication Activity Database

Mareš, Pavel; Kubová, Hana

2007-01-01

Roč. 59, Suppl.1 (2007), s. 12-13 ISSN 1734-1140. [Day of neuropsychopharmacology /16./. 06.09.2007-08.09.2007, Wroclaw] Institutional research plan: CEZ:AV0Z50110509 Keywords : postictal refractoriness * epileptic afterdischarges * rat Subject RIV: ED - Physiology

[Epileptic seizures during childbirth in a patient with idiopathic generalised epilepsy

NARCIS (Netherlands)

Voermans, N.C.; Zwarts, M.J.; Renier, W.O.; Bloem, B.R.

2005-01-01

During her first pregnancy, a 37-year-old woman with idiopathic generalised epilepsy that was adequately controlled with lamotrigine experienced a series of epileptic seizures following an elective caesarean section. The attacks were terminated with diazepam. The following day, she developed

Role of antithyroid drug treatment prior to radioiodine therapy in hyperthyroidism

International Nuclear Information System (INIS)

Das, B.K.; Pradhan, P.K.; Senthilnathan, M.S.; Malhotra, G.

2005-01-01

Full text: Radio Iodine (RI) therapy is preceded by anti thyroid drug treatment in most centres. There is a general notion that this is a pre-requisite for RI therapy. There have been some sporadic reports in the past emphasizing that euthyroid state is not necessary in all cases before RI. However, no prospective randomized study has been reported in recent literature. The aim of this prospective study was to find out whether prior treatment with anti thyroid drugs showed any advantage in comparison to direct application of radio iodine in hyperthyroid patients. Seventy-two clinically and bio chemically proven cases of hyperthyroidism were randomized into two groups , each with 36 patients. They were matched by age, sex and size of goiter. After establishment of the diagnosis the patients were either subjected to anti thyroid drug treatment (Group A) or given calculated dose of radio iodine (Group B). After being euthyroid for at least 4 weeks the Group A patients were asked to stop the drugs (Neomercazole) for 3-5 days and radio iodine was administered. Patients in both groups were prescribed beta blockers for 4-6 weeks. Average radio iodine dose in both groups was 5 ± 0.92 mCi. All patients were evaluated both clinically and bio chemically 3, 6, 12 months after the radio iodine application. The duration to achieve euthyroid state, patient tolerance and side effects if any were meticulously recorded. In the pre treated group 72.1, 83.4 and 97.2% of the patients attained euthyroid state at 3, 6, 12 months respectively. Five patients needed a second dose after 3 months. No side effect or complications were observed. In group B 77.7, 88.8 and 94.4% of patients achieved euthyroid status at 3, 6 and 12 months respectively. There was no side effects or complications noted. However, 16.7 and 22.2% of the patients in group A and 27.7 and 36.1% of the group B became hypothyroid at 6 and 12 months respectively. They were treated with Thyroxine supplementation. Overall

Grey matter volume in healthy and epileptic beagles using voxel-based morphometry – a pilot study

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Lisa Frank

2018-02-01

Full Text Available Abstract Background One of the most common chronic neurological disorders in dogs is idiopathic epilepsy (IE diagnosed as epilepsy without structural changes in the brain. In the current study the hypothesis should be proven that subtle grey matter changes occur in epileptic dogs. Therefore, magnetic resonance (MR images of one dog breed (Beagles were used to obtain an approximately uniform brain shape. Local differences in grey matter volume (GMV were compared between 5 healthy Beagles and 10 Beagles with spontaneously recurrent seizures (5 dogs with IE and 5 dogs with structural epilepsy (SE, using voxel-based morphometry (VBM. T1W images of all dogs were prepared using Amira 6.3.0 for brain extraction, FSL 4.1.8 for registration and SPM12 for realignment. After creation of tissue probability maps of cerebrospinal fluid, grey and white matter from control images to segment all extracted brains, GM templates for each group were constructed to normalize brain images for parametric statistical analysis, which was achieved using SPM12. Results Epileptic Beagles (IE and SE Beagles displayed statistically significant reduced GMV in olfactory bulb, cingulate gyrus, hippocampus and cortex, especially in temporal and occipital lobes. Beagles with IE showed statistically significant decreased GMV in olfactory bulb, cortex of parietal and temporal lobe, hippocampus and cingulate gyrus, Beagles with SE mild statistically significant GMV reduction in temporal lobe (p < 0.05; family- wise error correction. Conclusion These results suggest that, as reported in epileptic humans, focal reduction in GMV also occurs in epileptic dogs. Furthermore, the current study shows that VBM analysis represents an excellent method to detect GMV differences of the brain between a healthy dog group and dogs with epileptic syndrome, when MR images of one breed are used.

[Contemporary opinions on classification, pathogenesis and treatment of drug-resistant epilepsy].

Science.gov (United States)

Jóźwiak, Sergiusz

2007-01-01

Epilepsy is one of the most frequent neurological disorders, both in children and adult persons. About 0.5-1% of general population suffer from epilepsy, which means that about 50 million people in the world are affected. First years of life and very late adulthood are periods in human's life particularly predisposing to epilepsy. Repetitive epileptic seizures may cause many life-threatening situations and significantly lower patient's quality of life. To the most serious complications belong status epilepticus and sudden unexpected deaths due to epilepsy (SUDEP). Absences from work or school caused by seizures, difficulties in social life, frequent injuries and necessity of polytherapy are also important for patients. All these factors result in low self-esteem and poor quality of life. The main aim of the treatment was control of epileptic seizures. However, despite of new antiepileptic drugs developed almost every year, in one third of all patients with epilepsy seizures remain out of control. Those patients are regarded to have "drug-resistant epilepsy". Despite of significant scale of the problem, there is no one definition of the phenomenon. In the presented review the authors outline current definitions, recent opinions on pathogenesis and risk factors, and provide practical rules of pharmacotherapy of epilepsy, which should help to restrict drug-resistancy.

Impact of use of alcohol and illicit drugs by AIDS patients on adherence to antiretroviral therapy in Bahia, Brazil.

Science.gov (United States)

Teixeira, Celia; Dourado, Maria De Lourdes; Santos, Marcio P; Brites, Carlos

2013-05-01

Use of alcohol and illicit drugs is a common finding among HIV-infected individuals, but there are many open questions about its impact on adherence to antiretroviral therapy and virological outcomes. Our study aimed to evaluate the impact of the use of alcohol and illicit drugs on the adherence to antiretroviral therapy (ART) among patients starting ART in Salvador, Brazil. We followed up 144 AIDS patients initiating ART for a 6-month period. At baseline, they were interviewed about demographics, behavior, and use of illicit drugs and alcohol. All of them had HIV-1 RNA plasma viral load and CD4(+)/CD8(+) cells count measured before starting therapy. After 60 days of treatment they were asked to answer a new questionnaire on adherence to ART. All patients were monitored during the following months, and new CD4(+) cell count/HIV-1 RNA plasma viral load determinations were performed after 6 months of therapy. Optimal adherence to therapy was defined by self-reported questionnaire, by 95% use of prescribed drug doses, and by using plasma HIV-1 RNA viral load as a biological marker. A total of 61 (42.4%) patients reported alcohol use, 7 (4.9%) used illicit drugs, and 17 (11.8%) used both alcohol and illicit drugs. Being in a steady relationship was protective to nonadherence (95% CI: 0.18-0.84). Missing more than two medical visits was also associated with a 68% higher likelihood of nonadherence (95% CI: 0.10-1.02). After logistic regression we detected a higher risk of nonadherence for patients declaring use of alcohol plus illicit drugs (odds ratio=6.0; 95% CI: 1.78-20.28) or high-intensity use of alcohol (odds ratio=3.29; 95% CI: 1.83-5.92). AIDS patients using alcohol and/or illicit drugs are socially vulnerable, and need specific and flexible programs, combining mental health care, harm reduction strategies, and assisted drug therapy to maximize the chances of successful use of ART.

Specific Cell Targeting Therapy Bypasses Drug Resistance Mechanisms in African Trypanosomiasis.

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Juan D Unciti-Broceta

2015-06-01

Full Text Available African trypanosomiasis is a deadly neglected disease caused by the extracellular parasite Trypanosoma brucei. Current therapies are characterized by high drug toxicity and increasing drug resistance mainly associated with loss-of-function mutations in the transporters involved in drug import. The introduction of new antiparasitic drugs into therapeutic use is a slow and expensive process. In contrast, specific targeting of existing drugs could represent a more rapid and cost-effective approach for neglected disease treatment, impacting through reduced systemic toxicity and circumventing resistance acquired through impaired compound uptake. We have generated nanoparticles of chitosan loaded with the trypanocidal drug pentamidine and coated by a single domain nanobody that specifically targets the surface of African trypanosomes. Once loaded into this nanocarrier, pentamidine enters trypanosomes through endocytosis instead of via classical cell surface transporters. The curative dose of pentamidine-loaded nanobody-chitosan nanoparticles was 100-fold lower than pentamidine alone in a murine model of acute African trypanosomiasis. Crucially, this new formulation displayed undiminished in vitro and in vivo activity against a trypanosome cell line resistant to pentamidine as a result of mutations in the surface transporter aquaglyceroporin 2. We conclude that this new drug delivery system increases drug efficacy and has the ability to overcome resistance to some anti-protozoal drugs.

[Molecular fundamentals of drug interactions in the therapy of colorectal cancer].

Science.gov (United States)

Regulska, Katarzyna; Stanisz, Beata; Regulski, Miłosz; Gieremek, Paulina

2014-03-04

Rapid advances in the field of chemotherapy have resulted in the introduction of numerous antineoplastic drugs into clinical practice, which increased the efficiency of patient management. Also the prevalent use of combination treatment based on drug action synergy contributed to the improved clinical effect associated with cytotoxic drug administration. It seems, however, obvious that the multidirectional pharmacotherapy in oncology requires a thorough knowledge of drugs' pharmaceutical behavior in order to maximize their collective action and prevent the occurrence of unintended drug interactions that could potentially impair treatment effectiveness. In fact, drug interactions constitute a serious problem for current oncology primarily resulting from a narrow therapeutic index specific for the majority of anticancer drugs. This, in turn, indicates that even slight deviations of their pharmacokinetics could cause significant clinical consequences, manifested by alteration of the toxicological profile or reduction of therapeutic efficiency. Hence, the investigation of molecular aspects underlying the mechanisms of various drug interactions seems to be essential for proper and safe patient management. The present article is devoted to the extensive subject of drug interactions occurring in the therapy of colorectal cancer. It presents the available literature data on both positive and negative effects of interactions and it discusses their mechanisms complying with their classification into pharmacokinetic and pharmacodynamic ones.

Chlorpromazine-induced status epilepticus: A case report

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Momčilović-Kostadinović Dragana

2013-01-01

Full Text Available Introduction. It is largely known that some antipsychotic agents could have proconvulsive and proepileptogenic effects in some patients and could induce EEG abnormalities as well. However, the association of status epilepticus with certain antipsychotic drugs has been very rarely reported. Case Report. A case of an 18-year-old adolescent girl, with chlorpromazine therapy started for anxiety-phobic disorder was reported. Her personal history disclosed delayed psychomotor development. Shortly after the introduction of the neuroleptic chlorpromazine therapy in minimal daily dose (37.5 mg, she developed myoclonic status epilepticus, confirmed by the EEG records. Frequent, symmetrical bilateral myoclonic jerks and altered behavior were associated with bilateral epileptiform discharges of polyspikes and spike-wave complexes. This epileptic event lasted 3.5 hours and it was stopped by the parenteral administration of valproate and lorazepam; she was EEG monitored until stable remission. Status epilepticus as initial epileptic event induced by neuroleptic agent was not previously reported in our national literature. Conclusion. Introduction of chlorpromazine to a patient without history of seizures is associated with the evolution of an epileptic activity, including the occurrence of status epilepticus. Clinical evaluation of the risk factors possibly related to chlorpromazine-induced seizure is recommended in individual patients before administering this drug.

Atypical presentation in Rasmussen encephalitis: delayed late-onset periodic epileptic spasms.

Science.gov (United States)

Ferrari, Taíssa P F; Hamad, Ana P A; Caboclo, Luís Otávio S F; Centeno, Ricardo S; Zaninotto, Ana Luiza; Scattolin, Monica; Carrete Junior, Henrique; Lancellotti, Carmem L P; Yacubian, Elza Márcia T

2011-09-01

A five-and-a-half-year-old girl started experiencing progressive left hemiparesis at age two and a half years. At age five years and four months she started presenting clusters of asymmetric periodic epileptic spasms with no hypsarrhythmia. The ictal EEG showed periodic, constant and stereotyped complexes. Serial brain imaging revealed progressive atrophy of the right hemisphere with increased T2 signal on MRI. She underwent a right hemispherotomy, and histological examination showed signs of inflammation and features of focal cortical dysplasia (FCD). She has been seizure-free for 16 months. This case is unique in the following aspects: the presence of typical Rasmussen encephalitis features of progressive unilateral brain involvement without seizures, a delay of almost three years prior to seizure onset; an atypical seizure type presentation with periodic epileptic spasms and the presence of FCD associated with inflammatory changes. [Published with video sequences].

Epileptic MEG Spike Detection Using Statistical Features and Genetic Programming with KNN

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Turky N. Alotaiby

2017-01-01

Full Text Available Epilepsy is a neurological disorder that affects millions of people worldwide. Monitoring the brain activities and identifying the seizure source which starts with spike detection are important steps for epilepsy treatment. Magnetoencephalography (MEG is an emerging epileptic diagnostic tool with high-density sensors; this makes manual analysis a challenging task due to the vast amount of MEG data. This paper explores the use of eight statistical features and genetic programing (GP with the K-nearest neighbor (KNN for interictal spike detection. The proposed method is comprised of three stages: preprocessing, genetic programming-based feature generation, and classification. The effectiveness of the proposed approach has been evaluated using real MEG data obtained from 28 epileptic patients. It has achieved a 91.75% average sensitivity and 92.99% average specificity.

G2 checkpoint abrogator abates the antagonistic interaction between antimicrotubule drugs and radiation therapy

International Nuclear Information System (INIS)

Sui Meihua; Zhang Hongfang; Di Xiaoyun; Chang Jinjia; Shen Youqing; Fan Weimin

2012-01-01

Background and purpose: We previously demonstrated that radiation may arrest tumor cells at G2 phase, which in turn prevents the cytotoxicity of antimicrotubule drugs and results in antagonistic interaction between these two modalities. Herein we tested whether G2 abrogators would attenuate the above antagonistic interaction and improve the therapeutic efficacy of combination therapy between radiation and antimicrotubule drugs. Materials and methods: Breast cancer BCap37 and epidermoid carcinoma KB cell lines were administered with radiation, UCN-01 (a model drug of G2 abrogator), paclitaxel or vincristine, alone or in combinations. The antitumor activities of single and combined treatments were analyzed by a series of cytotoxic, apoptotic, cell cycle, morphological and biochemical assays. Results: UCN-01 significantly enhanced the cytotoxicity of radiation, antimitotic drugs, and their combined treatments in vitro. Further investigations demonstrated that UCN-01 attenuated radiation-induced G2 arrest, and subsequently repressed the inhibitory effect of radiation on drug-induced mitotic arrest and apoptosis. Conclusions: This is the first report demonstrating that G2 checkpoint abrogation represses the inhibitory effect of radiation on antimicrotubule drugs, which may be implicated in cancer combination therapy. Considering that G2 abrogators are under extensive evaluation for cancer treatment, our findings provide valuable information for this class of promising compounds.

A retrospective study of carbamazepine therapy in the treatment of idiopathic generalised epilepsy

LENUS (Irish Health Repository)

O'Connor, G

2011-05-01

Objective: The exacerbation of idiopathic generalised epilepsy (IGE) by some anti-epileptic drugs (AEDs) such as carbamazepine (CBZ) has been well documented. However, it is unclear whether IGE is always worsened by the use of CBZ, or whether some patients with IGE benefit from its use. \\r\

Electric Stimulation of Ear Reduces the Effect of Toll-Like Receptor 4 Signaling Pathway on Kainic Acid-Induced Epileptic Seizures in Rats

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En-Tzu Liao

2018-01-01

Full Text Available Epilepsy is a common clinical syndrome with recurrent neuronal discharges in the temporal lobe, cerebral cortex, and hippocampus. Clinical antiepileptic medicines are often ineffective or of little benefit in 30% of epileptic patients and usually cause severe side effects. Emerging evidence indicates the crucial role of inflammatory mediators in epilepsy. The current study investigates the role of toll-like receptor 4 (TLR4 and its underlying mechanisms in kainic acid- (KA- induced epileptic seizures in rats. Experimental KA injection successfully initiated an epileptic seizure accompanied by increased expression of TLR4 in the prefrontal cortex, hippocampus, and somatosensory cortex. In addition, calcium-sensitive phosphorylated Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα increased after the initiation of the epileptic seizure. Furthermore, downstream-phosphorylated signal-regulated kinase (ERK, c-Jun NH2-terminal protein kinase (JNK, and p38 kinase simultaneously increased in these brain areas. Moreover, the transcriptional factor phosphorylated nuclear factor-κB (pNF-κB increased, suggesting that nucleus transcription was affected. Furthermore, the aforementioned molecules decreased by an electric stimulation (ES of either 2 Hz or 15 Hz of the ear in the three brain areas. Accordingly, we suggest that ES of the ear can successfully control epileptic seizures by regulating the TLR4 signaling pathway and has a therapeutic benefit in reducing epileptic seizures.

Mouse neuroblastoma cell based model and the effect of epileptic events on calcium oscillations and neural spikes

Science.gov (United States)

Kim, Suhwan; Baek, Juyeong; Jung, Unsang; Lee, Sangwon; Jung, Woonggyu; Kim, Jeehyun; Kang, Shinwon

2013-05-01

Recently, Mouse neuroblastoma cells are considered as an attractive model for the study of human neurological and prion diseases, and intensively used as a model system in different areas. Among those areas, differentiation of neuro2a (N2A) cells, receptor mediated ion current, and glutamate induced physiological response are actively investigated. The reason for the interest to mouse neuroblastoma N2A cells is that they have a fast growing rate than other cells in neural origin with a few another advantages. This study evaluated the calcium oscillations and neural spikes recording of mouse neuroblastoma N2A cells in an epileptic condition. Based on our observation of neural spikes in mouse N2A cell with our proposed imaging modality, we report that mouse neuroblastoma N2A cells can be an important model related to epileptic activity studies. It is concluded that the mouse neuroblastoma N2A cells produce the epileptic spikes in vitro in the same way as produced by the neurons or the astrocytes. This evidence advocates the increased and strong level of neurotransmitters release by enhancement in free calcium using the 4-aminopyridine which causes the mouse neuroblastoma N2A cells to produce the epileptic spikes and calcium oscillation.

IONP-doped nanoparticles for highly effective NIR-controlled drug release and combination tumor therapy

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Fu X

2017-05-01

Full Text Available Xudong Fu,1 Xinjun Wang,1 Shaolong Zhou,1 Yanyan Zhang2 1The Fifth Affiliated Hospital of Zhengzhou University, 2School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China Abstract: Despite advances in controlled drug delivery, drug delivery systems (DDSs with controlled activated drug release and high spatial and temporal resolution are still required. Theranostic nanomedicine is capable of diagnosis, therapy, and monitoring the delivery and distribution of drug molecules and has received growing interest. In this study, a near-infrared light-controlled “off–on” DDS with magnetic resonance imaging and magnetic targeting properties was developed using a hybrid nanoplatform (carbon nanotubes [CNTs]-iron oxide nanoparticle. Doxorubicin (DOX and distearoyl-sn-glycero-3-phosphoethanolamine-PEG were adsorbed onto CNTs-iron oxide nanoparticle, and then to avoid the unexpected drug release during circulation, 1-myristyl alcohol was used to encapsulate the CNTs–drug complex. Herein, multifunctional DOX-loaded nanoparticles (NPs with “off–on” state were developed. DOX-NPs showed an obvious “off–on” effect (temperature increase, drug release controlled by near-infrared light in vitro and in vivo. In the in vivo and in vitro studies, DOX-NPs exhibited excellent magnetic resonance imaging ability, magnetic targeting property, high biosafety, and high antitumor combined therapeutic efficacy (hyperthermia combined with chemotherapy. These results highlight the great potential of DOX-NPs in the treatment of cancer. Keywords: controlled drug release, magnetic targeting, MRI, combination therapy

APPLICABILITY OF THE NON STEROID ANTIINFLAMMATORY DRUGS IN FEVER THERAPY OF CHILDREN

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O.A. Mubarakshina

2008-01-01

Full Text Available The non steroid anti-inflammatory drugs are widely applied in the pediatric practices for the fever therapy among children. While choosing the medications from this group to prescribe them to the children, it is essential to get guided towards the highly efficient medications with the least risk of the side effects. Only Paracetamol and ibuprofen are fully compliant with this requirement. They are officially recommended by who as the anti febrile medications for use in pediatrics. In the given article, the author reviews the advantages of ibuprofen over to Paracetamol based on the data from the foreign randomized research. She pays certain attention to the safety issues during the ibuprofen based treatment and to the opportunities of the combined Paracetamol and ibuprofen based therapy.Key words: fever, treatment, non steroid anti-inflammatory drugs, children.

Pulmonary fibrosis associated with psychotropic drug therapy: a case report

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Thornton Clare

2009-11-01

Full Text Available Abstract Introduction Sertraline and Risperidone are commonly used psychotropic drugs. Sertraline has previously been associated with eosinopilic pneumonia. Neither drug is recognised as a cause of diffuse fibrotic lung disease. Our report represents the first such case. Case Presentation We describe the case of a 33 year old Asian male with chronic schizophrenia who had been treated for three years with sertraline and risperidone. He presented to hospital in respiratory failure following a six month history of progressive breathlessness. High resolution CT scan demonstrated diffuse pulmonary fibrosis admixed with patchy areas of consolidation. Because the aetiology of this man's diffuse parenchymal lung disease remained unclear a surgical lung biopsy was undertaken. Histological assessment disclosed widespread fibrosis with marked eosinophillic infiltration and associated organising pneumonia - features all highly suggestive of drug induced lung disease. Following withdrawal of both sertraline and risperidone and initiation of corticosteroid therapy the patient's respiratory failure resolved and three years later he remains well albeit limited by breathlessness on heavy exertion. Conclusion Drug induced lung disease can be rapidly progressive and if drug exposure continues may result in respiratory failure and death. Prompt recognition is critical as drug withdrawal may result in marked resolution of disease. This case highlights sertraline and risperidone as drugs that may, in susceptible individuals, cause diffuse pulmonary fibrosis.

Drug utilization and therapy provision patterns by prescriber types among patients with systemic lupus erythematosus in Korea

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Shin S

2017-10-01

Full Text Available Sooyoung Shin College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST, Ajou University, Yeongtong-gu, Suwon, Republic of Korea Background: Systemic lupus erythematosus (SLE poses a growing challenge for healthcare systems, affecting an increasing number of people in Korea. This study aimed to investigate the prescribing patterns of SLE therapies and to compare common drug regimens prescribed by provider types.Methods: Sampled national health insurance claims data in 2015 were used to select eligible SLE patients. Frequency analyses were carried out regarding patient characteristics related to relevant SLE prescriptions. Patient-days were calculated per substance and per drug class and then categorized by provider types. Differences in drug utilization trends among the main types of providers were examined with the chi-square test.Results: A total of 2,074 patients with SLE were selected for study inclusion. Systemic corticosteroid therapy was provided for up to 67.9% of patients, frequently in conjunction with other SLE therapies. About 33.2% and 18.7% of steroid users were treated for more than 150 days and 300 days during the study period, respectively. The provider group that most frequently prescribed systemic corticosteroids was dermatologists. Hydroxychloroquine, an antimalarial considered pivotal to SLE management, was prescribed for only 32.4% of patients, predominantly by rheumatologists. Antimalarial therapy was associated with the longest therapy duration (257.7±120.1 days, followed by immunosuppressant therapy (187.0±153.0 days. Prescription rates of antimalarials and immunosuppressants were substantially lower in primary care doctor group and particularly in dermatologist group, compared to rheumatologist group (P-value associated with prescription patterns by provider types was <0.001 for both drug classes.Conclusion: The drug utilization patterns among the main provider groups commonly

Therapies for inborn errors of metabolism: what has the orphan drug act delivered?

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Talele, Sonali S; Xu, Kui; Pariser, Anne R; Braun, M Miles; Farag-El-Massah, Sheiren; Phillips, M Ian; Thompson, Barry H; Coté, Timothy R

2010-07-01

The 1983 US Orphan Drug Act established a process through which promising therapies are designated as orphan products and, later, with satisfactory safety and efficacy data, receive marketing approval and fiscal incentives. We examined accomplishments in drug development for inborn errors of metabolism (IEMs). Food and Drug Administration data were used to identify orphan product designations and approvals for IEMs, and the trends for the past 26 years were summarized. Individual clinical development times (CDTs) from filing investigational new drug application to marketing approval were determined. We examined 1956 orphan product designations from 1983 through 2008 and found 93 (4.8%) for IEMs. Of those, 24 (25.8%) received marketing approval. This proportion of approval was significantly (P = .036) higher than that for non-IEM orphan products (17%). Among the IEM products, disorders of complex molecules received the most designations and approvals (61 and 11, respectively). Among the subgroups, lysosomal storage diseases received the most designations and approvals (43 and 9, respectively), whereas mitochondrial diseases (other than fatty acid oxidation disorders) received 7 designations with no approvals. We then examined the CDTs for the approved IEM products and found a median of 6.4 years (range: 2.6-25.1 years). Biological products had significantly shorter CDTs than drugs (mean: 4.6 vs 11.0 years; P = .003). For 26 years, the Orphan Drug Act has generated new therapies for IEMs. Why some IEMs have motivated successful drug development and others have not remains enigmatic; yet the needs of IEM patients without treatment are a certainty.

Process Pharmacology: A Pharmacological Data Science Approach to Drug Development and Therapy.

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Lötsch, Jörn; Ultsch, Alfred

2016-04-01

A novel functional-genomics based concept of pharmacology that uses artificial intelligence techniques for mining and knowledge discovery in "big data" providing comprehensive information about the drugs' targets and their functional genomics is proposed. In "process pharmacology", drugs are associated with biological processes. This puts the disease, regarded as alterations in the activity in one or several cellular processes, in the focus of drug therapy. In this setting, the molecular drug targets are merely intermediates. The identification of drugs for therapeutic or repurposing is based on similarities in the high-dimensional space of the biological processes that a drug influences. Applying this principle to data associated with lymphoblastic leukemia identified a short list of candidate drugs, including one that was recently proposed as novel rescue medication for lymphocytic leukemia. The pharmacological data science approach provides successful selections of drug candidates within development and repurposing tasks. © 2016 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Clinical utility of adjunctive retigabine in partial onset seizures in adults

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Rejdak K

2012-01-01

Full Text Available Konrad Rejdak1, Jarogniew J Luszczki2,3, Barbara Blaszczyk4, Roman Chwedorowicz5, Stanislaw J Czuczwar2,51Department of Neurology, Medical University of Lublin, Lublin, 2Department of Pathophysiology, Medical University of Lublin, Lublin, 3Isobolography Analysis Laboratory, Institute of Agricultural Medicine, Lublin, 4Faculty of Health Sciences, High School of Economics and Law, Kielce, 5Department of Physiopathology, Institute of Agricultural Medicine, Lublin, PolandAbstract: In ~30% of epileptic patients, full seizure control is not possible, which is why the search for novel antiepileptic drugs continues. Retigabine exhibits a mechanism of action that is not shared by the available antiepileptic drugs. This antiepileptic enhances potassium currents via Kv7.2–7.3 channels, which very likely results from destabilization of a closed conformation or stabilization of the open conformation of the channels. Generally, the pharmacokinetics of retigabine are linear and the drug undergoes glucuronidation and acetylation. Results from clinical trials indicate that, in the form of an add-on therapy, retigabine proves an effective drug in refractory epileptic patients. The major adverse effects of the add-on treatment are dizziness, somnolence, and fatigue. This epileptic drug is also considered for other conditions – neuropathic pain, affective disorders, stroke, or even Alzheimer’s disease.Keywords: antiepileptic drugs, epilepsy, seizure control

18F-FDG PET Reveals Fronto-temporal Dysfunction in Children with Fever-Induced Refractory Epileptic Encephalopathy

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Mazzuca, M.; Dulac, O.; Chiron, C.; Jambaque, I.; Hertz-Pannier, L.; Bouilleret, V.; Archambaud, F.; Rodrigo, S.; Dulac, O.; Chiron, C.; Jambaque, I.; Hertz-Pannier, L.; Bouilleret, V.; Archambaud, F.; Rodrigo, S.; Chiron, C.; Hertz-Pannier, L.; Rodrigo, S.; Dulac, O.; Chiron, C.; Caviness, V.

2011-01-01

Fever-induced refractory epileptic encephalopathy in school-age children (FIRES) is a recently described epileptic entity whose etiology remains unknown. Brain abnormalities shown by MRI are usually limited to mesial-temporal structures and do not account for the catastrophic neuro-psychologic findings. Methods: We conducted FIRES studies in 8 patients, aged 6-13 y, using 18 F-FDG PET to disclose eventual neo-cortical dysfunction. Voxel-based analyses of cerebral glucose metabolism were performed using statistical parametric mapping and an age-matched control group. Results: Group analysis revealed a widespread inter-ictal hypo-metabolic network including the temporo-parietal and orbito-frontal cortices bilaterally. The individual analyses in patients identified hypo-metabolic areas corresponding to the predominant electroencephalograph foci and neuro-psychologic deficits involving language, behavior, and memory. Conclusion: Despite clinical heterogeneity, 18 F-FDG PET reveals a common network dysfunction in patients with sequelae due to fever-induced refractory epileptic encephalopathy. (authors)

Should pediatric patients with hyperlipidemia receive drug therapy?

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Bhatnagar, Deepak

2002-01-01

Hyperlipidemia is now established as a major risk factor for causation of coronary heart disease (CHD) in adults; however, there is much debate on the level of coronary risk at which lipid-lowering drugs should be used. These issues of possible harm or lack of benefit from long-term use of lipid-lowering therapy, and cost effectiveness, are also pertinent in the pediatric setting. Evidence from several countries indicates that children have an increasing prevalence of obesity, hyperlipidemia and type 2 diabetes mellitus. Children who have high serum lipids 'track' these increased levels into adulthood. In some countries there is a trend to screen children for hypercholesterolemia. Family history itself is a poor discriminator in determining which children need to be screened and treated. Estimation of apolipoprotein B and/or apolipoprotein E genotype can improve prediction. Measuring high density lipoprotein cholesterol also helps, but obesity appears to be the best marker for screening children at high risk. These considerations should not cloud the need for case finding and treatment of children with genetic disorders. Low fat diets have been shown to be well tolerated and effective in children; however, there are no major long-term studies demonstrating harm or benefit in those on lipid-lowering drugs. Nevertheless, concerns regarding the psychological effect and the theoretical metabolic effects of long-term lipid lowering remain. Lipid-lowering drugs should be generally restricted to children with genetic disorders of lipid metabolism. Children with diabetes mellitus, hypertension or nonlipid-related inherited disorders leading to premature CHD in adults should be treated with diet, and with lipid-lowering drugs when they reach adulthood. Children with secondary hyperlipidemia should be assessed individually. A number of drugs and nutriceuticals are available for use in children, but only a few drugs are licensed for use in children.

Indefinite antithyroid drug therapy in toxic Graves′ disease: What are the cons

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Rajesh Rajput

2013-01-01

Full Text Available Existing treatment modalities for Graves′ disease includes antithyroid drugs (ATDs, radioactive iodine, and surgery. There has been a lack of general agreement as to which therapy is the best as none is ideal since all effectively restore euthyroidism, but with some limitations. Previously, therapies were selected with the goal of achieving euthyroidism. Instead, hypothyroidism is now the goal of treatment, to ensure that hyperthyroidism does not recur. Current evidences suggest that high relapse rate and not so rare fatal side effects seen with ATD therapy compel one to consider other definite modes of treatment like radiotherapy and surgery for toxic Graves′ disease after discussing this with the patient.

Indefinite antithyroid drug therapy in toxic Graves’ disease: What are the cons

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Rajput, Rajesh; Goel, Vasudha

2013-01-01

Existing treatment modalities for Graves’ disease includes antithyroid drugs (ATDs), radioactive iodine, and surgery. There has been a lack of general agreement as to which therapy is the best as none is ideal since all effectively restore euthyroidism, but with some limitations. Previously, therapies were selected with the goal of achieving euthyroidism. Instead, hypothyroidism is now the goal of treatment, to ensure that hyperthyroidism does not recur. Current evidences suggest that high relapse rate and not so rare fatal side effects seen with ATD therapy compel one to consider other definite modes of treatment like radiotherapy and surgery for toxic Graves’ disease after discussing this with the patient. PMID:24251229

Neuropsychological effects of antiepileptic drugs (carbamazepine versus valproate in adult males with epilepsy

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Ghaydaa A Shehata

2009-10-01

Full Text Available Ghaydaa A Shehata,1 Abd El-aziz M Bateh,2 Sherifa A Hamed,1 Tarek A Rageh,1 Yaser B Elsorogy11Department of Neurology and Psychiatry, Faculty of Medicine, Assiut University, Egypt; 2Department of Psychology, Faculty of Arts, Banha University, EgyptPurpose: To evaluate the effect of antiepileptic drugs (AEDs on cognition and behavior in adult epileptic males controlled on treatment with conventional antiepileptic medications. Methods: Cognitive, mood, behavior and personality traits were assessed in 45 epileptic patients treated with carbamazepine and/or valproate and free of seizures for ≥1 year. Thirty-four newly diagnosed or untreated patients with epilepsy and 58 matched healthy subjects were also included for comparison. A battery of psychometric tests was utilized including Stanford-Binet (4th edition, Beck Inventory for Depression, Aggressive Scale and Eysenck Personality Questionnaire.Results: Compared to matched control subjects, treated and untreated epileptic patients had poor performance in different cognitive and behavioral functions testing. Treated patients had worse scores in memory for digits forward and backward, total short-term memory, extroversion and psychosis. The duration of AEDs intake was correlated with memory of objects (r = -0.323; P = 0.030, bead memory (r = -0.314; P = 0.036 and total nonverbal short-term memory (r = -0.346; P = 0.020. Treated and untreated epileptic patients had poor performance of similar extent in behavioral functions testing (depression, aggression and neurosis. The dose of AEDs was correlated with testing scores for neurosis (r = 0.307; P = 0.040, verbal aggression (r = 0.483; P = 0.001 and nonverbal aggression (r = 0.526; P = 0.000, and duration of drug intake was correlated with scores for depression (r = 0.384; P = 0.009, psychosis (r = 0.586; P = 0.0001 and nonverbal aggression (r = 0.300; P = 0.045.Conclusions: This study provides support for the notion that AEDs can impair performance

Diagnostic and therapeutic problems in pediatric epileptology

International Nuclear Information System (INIS)

Faienza, C.; Prati, G.L.

1988-01-01

The topics covered include a critical review of the ILEA classification of epilepsy in children, genesis of the epileptic seizures, recent advances on the pathology of early epileptic encephalopathies, etiologic and prognostic factors in drug-resistant epilepsies, and a very interesting approach on cyclic modulating processes and electrical activity in the brain. Detailed information on the usefulness of brain mapping and magnetic resonance has also been expertly provided. In the second part of the volume the management of epilepsy, including criteria for starting and interrupting AED, the usefulness and limitation of AED monitoring, neurosurgical approach in the diagnosis and therapy of childhood epilepsy, adverse effects of AED in pediatric age, and new research in AED therapy has been explored. refs.; figs.; tabs

Classification of epileptic seizures using wavelet packet log energy and norm entropies with recurrent Elman neural network classifier.

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Raghu, S; Sriraam, N; Kumar, G Pradeep

2017-02-01

Electroencephalogram shortly termed as EEG is considered as the fundamental segment for the assessment of the neural activities in the brain. In cognitive neuroscience domain, EEG-based assessment method is found to be superior due to its non-invasive ability to detect deep brain structure while exhibiting superior spatial resolutions. Especially for studying the neurodynamic behavior of epileptic seizures, EEG recordings reflect the neuronal activity of the brain and thus provide required clinical diagnostic information for the neurologist. This specific proposed study makes use of wavelet packet based log and norm entropies with a recurrent Elman neural network (REN) for the automated detection of epileptic seizures. Three conditions, normal, pre-ictal and epileptic EEG recordings were considered for the proposed study. An adaptive Weiner filter was initially applied to remove the power line noise of 50 Hz from raw EEG recordings. Raw EEGs were segmented into 1 s patterns to ensure stationarity of the signal. Then wavelet packet using Haar wavelet with a five level decomposition was introduced and two entropies, log and norm were estimated and were applied to REN classifier to perform binary classification. The non-linear Wilcoxon statistical test was applied to observe the variation in the features under these conditions. The effect of log energy entropy (without wavelets) was also studied. It was found from the simulation results that the wavelet packet log entropy with REN classifier yielded a classification accuracy of 99.70 % for normal-pre-ictal, 99.70 % for normal-epileptic and 99.85 % for pre-ictal-epileptic.

Molecular fundamentals of drug interactions in the therapy of colorectal cancer

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Katarzyna Regulska

2014-03-01

Full Text Available Rapid advances in the field of chemotherapy have resulted in the introduction of numerous antineoplastic drugs into clinical practice, which increased the efficiency of patient management. Also the prevalent use of combination treatment based on drug action synergy contributed to the improved clinical effect associated with cytotoxic drug administration. It seems, however, obvious that the multidirectional pharmacotherapy in oncology requires a thorough knowledge of drugs’ pharmaceutical behavior in order to maximize their collective action and prevent the occurrence of unintended drug interactions that could potentially impair treatment effectiveness. In fact, drug interactions constitute a serious problem for current oncology primarily resulting from a narrow therapeutic index specific for the majority of anticancer drugs. This, in turn, indicates that even slight deviations of their pharmacokinetics could cause significant clinical consequences, manifested by alteration of the toxicological profile or reduction of therapeutic efficiency. Hence, the investigation of molecular aspects underlying the mechanisms of various drug interactions seems to be essential for proper and safe patient management. The present article is devoted to the extensive subject of drug interactions occurring in the therapy of colorectal cancer. It presents the available literature data on both positive and negative effects of interactions and it discusses their mechanisms complying with their classification into pharmacokinetic and pharmacodynamic ones.

SCN1A, ABCC2 and UGT2B7 gene polymorphisms in association with individualized oxcarbazepine therapy.

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Ma, Chun-Lai; Wu, Xun-Yi; Jiao, Zheng; Hong, Zhen; Wu, Zhi-Yuan; Zhong, Ming-Kang

2015-01-01

Associations between the effects of SCN1A, SCN2A, ABCC2 and UGT2B7 genetic polymorphisms and oxcarbazepine (OXC) maintenance doses in Han Chinese epileptic patients were investigated. Genetic polymorphisms were detected in 184 epileptic patients receiving OXC monotherapy by high-resolution melting curve and TaqMan method. Carriers of the SCN1A IVS5-91G>A, UGT2B7 c.802T>C and ABCC2 c.1249G>A variant alleles required significantly higher OXC maintenance doses than noncarriers (p GA > AA. SCN1A, UGT2B7 and ABCC2 genetic polymorphisms are associated with OXC maintenance doses and may be useful for the personalization of OXC therapy in epileptic patients. Further studies are needed. Original submitted 6 June 2014; Revision submitted 5 September 2014.

De novo mutations in HCN1 cause early infantile epileptic encephalopathy.

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Nava, Caroline; Dalle, Carine; Rastetter, Agnès; Striano, Pasquale; de Kovel, Carolien G F; Nabbout, Rima; Cancès, Claude; Ville, Dorothée; Brilstra, Eva H; Gobbi, Giuseppe; Raffo, Emmanuel; Bouteiller, Delphine; Marie, Yannick; Trouillard, Oriane; Robbiano, Angela; Keren, Boris; Agher, Dahbia; Roze, Emmanuel; Lesage, Suzanne; Nicolas, Aude; Brice, Alexis; Baulac, Michel; Vogt, Cornelia; El Hajj, Nady; Schneider, Eberhard; Suls, Arvid; Weckhuysen, Sarah; Gormley, Padhraig; Lehesjoki, Anna-Elina; De Jonghe, Peter; Helbig, Ingo; Baulac, Stéphanie; Zara, Federico; Koeleman, Bobby P C; Haaf, Thomas; LeGuern, Eric; Depienne, Christel

2014-06-01

Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to cationic Ih current in neurons and regulate the excitability of neuronal networks. Studies in rat models have shown that the Hcn1 gene has a key role in epilepsy, but clinical evidence implicating HCN1 mutations in human epilepsy is lacking. We carried out exome sequencing for parent-offspring trios with fever-sensitive, intractable epileptic encephalopathy, leading to the discovery of two de novo missense HCN1 mutations. Screening of follow-up cohorts comprising 157 cases in total identified 4 additional amino acid substitutions. Patch-clamp recordings of Ih currents in cells expressing wild-type or mutant human HCN1 channels showed that the mutations had striking but divergent effects on homomeric channels. Individuals with mutations had clinical features resembling those of Dravet syndrome with progression toward atypical absences, intellectual disability and autistic traits. These findings provide clear evidence that de novo HCN1 point mutations cause a recognizable early-onset epileptic encephalopathy in humans.

Commercialization strategy of the herbal composition HemoHIM as a complementary drug for anti-cancer therapies

Energy Technology Data Exchange (ETDEWEB)

Jo, Sungkee; Jung, Uhee; Park, Haeran

2013-01-15

Ο Purpose - Establishment of strategy for the development of HemoHIM as a complementary drug for cancer therapies including non-clinical data preparation, obtainment of a research project grant, base of manufacturing process and raw material standardization Ο Research Results - Examination and confirmation of the essential requirements to develop the complementary drug for anticancer therapies by consulting with Korea FDA, and clinical CRO, and medical experts (animal efficacy study, toxicological safety test, standard analytical method, raw material standardization) - Obtainment of a governmental research project for 3 years from Ministry of Health and Welfare to develop HemoHIM as an complementary herbal drug for anti-cancer therapies - Acquisition of fundamental data on the manufacturing process and the raw material standardization for the optimal efficacy of HemoHIM Ο Expected benefit - Planning to get the approval of IND from Korea FDA by 2015 after completing the non-clinical study through the on-going project from Ministry of Health and Welfare - Planning to commercialize the product by 2017.

Commercialization strategy of the herbal composition HemoHIM as a complementary drug for anti-cancer therapies

International Nuclear Information System (INIS)

Jo, Sungkee; Jung, Uhee; Park, Haeran

2013-01-01

Ο Purpose - Establishment of strategy for the development of HemoHIM as a complementary drug for cancer therapies including non-clinical data preparation, obtainment of a research project grant, base of manufacturing process and raw material standardization Ο Research Results - Examination and confirmation of the essential requirements to develop the complementary drug for anticancer therapies by consulting with Korea FDA, and clinical CRO, and medical experts (animal efficacy study, toxicological safety test, standard analytical method, raw material standardization) - Obtainment of a governmental research project for 3 years from Ministry of Health and Welfare to develop HemoHIM as an complementary herbal drug for anti-cancer therapies - Acquisition of fundamental data on the manufacturing process and the raw material standardization for the optimal efficacy of HemoHIM Ο Expected benefit - Planning to get the approval of IND from Korea FDA by 2015 after completing the non-clinical study through the on-going project from Ministry of Health and Welfare - Planning to commercialize the product by 2017

Preliminary study of the association between the elimination parameters of phenytoin and phenobarbital.

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Methaneethorn, Janthima; Panomvana, Duangchit; Vachirayonstien, Thaveechai

2017-09-26

Therapeutic drug monitoring is essential for both phenytoin and phenobarbital therapy given their narrow therapeutic indexes. Nevertheless, the measurement of either phenytoin or phenobarbital concentrations might not be available in some rural hospitals. Information assisting individualized phenytoin and phenobarbital combination therapy is important. This study's objective was to determine the relationship between the maximum rate of metabolism of phenytoin (Vmax) and phenobarbital clearance (CLPB), which can serve as a guide to individualized drug therapy. Data on phenytoin and phenobarbital concentrations of 19 epileptic patients concurrently receiving both drugs were obtained from medical records. Phenytoin and phenobarbital pharmacokinetic parameters were studied at steady-state conditions. The relationship between the elimination parameters of both drugs was determined using simple linear regression. A high correlation coefficient between Vmax and CLPB was found [r=0.744; pphenobarbital. These proposed equations can be of use in aiding individualized drug therapy.

Modeling the effects of space structure and combination therapies on phenotypic heterogeneity and drug resistance in solid tumors.

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Lorz, Alexander; Lorenzi, Tommaso; Clairambault, Jean; Escargueil, Alexandre; Perthame, Benoît

2015-01-01

Histopathological evidence supports the idea that the emergence of phenotypic heterogeneity and resistance to cytotoxic drugs can be considered as a process of selection in tumor cell populations. In this framework, can we explain intra-tumor heterogeneity in terms of selection driven by the local cell environment? Can we overcome the emergence of resistance and favor the eradication of cancer cells by using combination therapies? Bearing these questions in mind, we develop a model describing cell dynamics inside a tumor spheroid under the effects of cytotoxic and cytostatic drugs. Cancer cells are assumed to be structured as a population by two real variables standing for space position and the expression level of a phenotype of resistance to cytotoxic drugs. The model takes explicitly into account the dynamics of resources and anticancer drugs as well as their interactions with the cell population under treatment. We analyze the effects of space structure and combination therapies on phenotypic heterogeneity and chemotherapeutic resistance. Furthermore, we study the efficacy of combined therapy protocols based on constant infusion and bang-bang delivery of cytotoxic and cytostatic drugs.

Rational use and interpretation of urine drug testing in chronic opioid therapy.

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Reisfield, Gary M; Salazar, Elaine; Bertholf, Roger L

2007-01-01

Urine drug testing (UDT) has become an essential feature of pain management, as physicians seek to verify adherence to prescribed opioid regimens and to detect the use of illicit or unauthorized licit drugs. Results of urine drug tests have important consequences in regard to therapeutic decisions and the trust between physician and patient. However, reliance on UDT to confirm adherence can be problematic if the results are not interpreted correctly, and evidence suggests that many physicians lack an adequate understanding of the complexities of UDT and the factors that can affect test results. These factors include metabolic conversion between drugs, genetic variations in drug metabolism, the sensitivity and specificity of the analytical method for a particular drug or metabolite, and the effects of intentional and unintentional interferants. In this review, we focus on the technical features and limitations of analytical methods used for detecting drugs or their metabolites in urine, the statistical constructs that are pertinent to ordering UDT and interpreting test results, and the application of these concepts to the clinical monitoring of patients maintained on chronic opioid therapy.

Selected pharmacokinetic issues of the use of antiepileptic drugs and parenteral nutrition in critically ill patients.

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Salih, Muhannad R M; Bahari, Mohd Baidi; Abd, Arwa Y

2010-12-31

To conduct a systematic review for the evidence supporting or disproving the reality of parenteral nutrition- antiepileptic drugs interaction, especially with respect to the plasma protein-binding of the drug. The articles related to the topic were identified through Medline and PubMed search (1968-Feburary 2010) for English language on the interaction between parenteral nutrition and antiepileptic drugs; the search terms used were anti-epileptic drugs, parenteral nutrition, and/or interaction, and/or in vitro. The search looked for prospective randomized and nonrandomized controlled studies; prospective nonrandomized uncontrolled studies; retrospective studies; case reports; and in vitro studies. Full text of the articles were then traced from the Universiti Sains Malaysia (USM) library subscribed databases, including Wiley-Blackwell Library, Cochrane Library, EBSCOHost, OVID, ScienceDirect, SAGE Premier, Scopus, SpringerLINK, and Wiley InterScience. The articles from journals not listed by USM library were traced through inter library loan. There were interactions between parenteral nutrition and drugs, including antiepileptics. Several guidelines were designed for the management of illnesses such as traumatic brain injuries or cancer patients, involving the use of parenteral nutrition and antiepileptics. Moreover, many studies demonstrated the in vitro and in vivo parenteral nutrition -drugs interactions, especially with antiepileptics. There was no evidence supporting the existence of parenteral nutrition-antiepileptic drugs interaction. The issue has not been studied in formal researches, but several case reports and anecdotes demonstrate this drug-nutrition interaction. However, alteration in the drug-free fraction result from parenteral nutrition-drug (i.e. antiepileptics) interactions may necessitate scrupulous reassessment of drug dosages in patients receiving these therapies. This reassessment may be particularly imperative in certain clinical situations

Association Between the Occurrence of Adverse Drug Events and Modification of First-Line Highly Active Antiretroviral Therapy in Ghanaian HIV Patients.

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Tetteh, Raymond A; Nartey, Edmund T; Lartey, Margaret; Mantel-Teeuwisse, Aukje K; Leufkens, Hubert G M; Yankey, Barbara A; Dodoo, Alexander N O

2016-11-01

Patients initiated on highly active antiretroviral therapy (HAART) generally remain on medication indefinitely. A modification in the HAART regimen may become necessary because of possible acute or chronic toxicities, concomitant clinical conditions, development of virological failure or the advent of adverse drug events. The study documents adverse drug events of HIV-positive Ghanaian patients with HAART modifications. It also investigates the association between documented adverse drug events and HAART modification using an unmatched case-control study design. The study was conducted in the Fevers Unit of the Korle Bu Teaching Hospital and involved patients who attended the HIV Care Clinic between January 2004 and December 2009. Data from 298 modified therapy patients (cases) were compared with 298 continuing therapy patients (controls) who had been on treatment for at least 1 month before the end of study. Controls were sampled from the same database of a cohort of HIV-positive patients on HAART, at the time a case occurred, in terms of treatment initiation ±1 month. Data were obtained from patients' clinical folders and the HIV clinic database linked to the pharmacy database. The nature of the documented adverse drug events of the cases was described and the association between the documented adverse drug events and HAART modification was determined by logistic regression with reported odds ratios (ORs) and their 95 % confidence interval (CI). Among the 298 modified therapy patients sampled in this study, 52.7 % of them had at least one documented adverse drug event. The most documented adverse drug event was anaemia, recorded in 18.5 % of modified therapy patients, all of whom were on a zidovudine-based regimen. The presence of documented adverse drug events was significantly associated with HAART modification [adjusted OR = 2.71 (95 % CI 2.11-3.48), p < 0.001]. Among HIV patients on HAART, adverse drug events play a major role in treatment

Restriction of the spread of epileptic discharges in cats by means of Bragg peak, intracranial irradiation

International Nuclear Information System (INIS)

Gaffey, C.T.; Montoya, V.J.; Lyman, J.T.; Howard, J.

1981-01-01

Adult male cats with a single epileptic focus receive neon ion Bragg peak radiation at the Bevalac at Lawrence Berkeley Laboratory. Bragg peak radiation is deposited in a thin disc of brain tissue beneath an epileptogenic focus produced with alumina cream. Paroxysmal electroencephalograms (EEGs) from the occipital cortex of cats confirm the biolectric changes in the pathogenesis of epilepsy. Distant spread of seizure activity occurs when the cells in the cortical focus fire a series of relatively simultaneous spikes at high frequency with sufficient intensity to develop self-sustained discharges in remote brain areas. The development of a 'mirror focus' in the EEG records in the contralateral cortex gives a measure of the distances paroxysmal discharges spread. Interhemispheric responses (IHR) that travel from the alumina-treated cortex via the corpus callosum to the contralateral cortex are a second measure of pathways over which paroxysmal discharges spread. In cat studies Bragg peak radiation is positioned beneath the epileptic cortical focus. Various heavy ion doses are employed to test whether an absorbed dose per cat is sufficient to block the transmission of epileptic activity as a function of the post-irradiation time. The relationship between neon ion dose and the post-irradiation time for the loss of IHR is a measure of the physiological dissociation of the epileptic brain tissue from the remainder of the brain. The loss of the 'mirror focus' in EEG records agrees with the IHR findings. (author)

How large must an epileptic focus be to cause an electrographic status epilepticus--a case report.

Science.gov (United States)

Fauser, Susanne; Schulze-Bonhage, Andreas

2004-10-01

Based on experimental data from animal studies different theories regarding the size of an epileptic focus have been postulated which range from single pacemaker cells to extended neuronal networks. We report a case which gives further information about the size of a human epileptic focus which can trigger manifest epileptic seizures. We report a 22-year-old man with medically refractory temporal lobe epilepsy. This patient suffered from brief complex partial seizures and frequent epigastric auras. To differentiate a mesiotemporal from a temporolateral seizure origin the patient was implanted with a 10 contact depth electrode from a posterior approach into the right hippocampus, and additional temporobasal/temporolateral subdural strip electrodes. Depth recordings revealed an electrographic status with continuous rhythmic sharp wave activity (1 Hz), the field of which was confined to a diameter of less than 1 cm in the anterior hippocampus, whereas temporobasal subdural strip electrodes did not display this activity. Periodically, spread of this activity occurred to the amygdala, to the posterior part of the hippocampus, and less often to the temporobasal cortex. Most seizure patterns remained subclinical, few of them became symptomatic as partial seizures. This case demonstrates that a hippocampal epileptic focus causing electrographic focal status epilepticus may be limited to a volume of less than 1 cm in diameter. This observation is discussed with regard to implantation strategies and to possible superselective resective or modulatory approaches in the treatment of such limited epileptogenic areas.

HSA/PSS coated gold nanorods as thermo-triggered drug delivery vehicles for combined cancer photothermal therapy and chemotherapy

Science.gov (United States)

Tu, Ting-Yu; Yang, Shu-Jyuan; Wang, Chung-Hao; Lee, Shin-Yu; Shieh, Ming-Jium

2018-02-01

Drug delivery systems combined multimodal therapy strategies are very promising in cancer theranostic applications. In this work, a new drug-delivery vehicles based on human serum albumin (HSA)-coated gold nanorods (GNR/PSS/HSA NPs) was developed. The success of coating was verified by transmission electron microscopy (TEM), zeta potential and fourier transform infrared spectroscopy (FTIR). Furthermore, it is demonstrated that doxorubicin (DOX) is successfully loaded among multilayered gold nanorods by the electrostatic and hydrophobic force, and DOX@GNR/PSS/HSA NPs were highly biocompatible and stable in various physiological solutions. The NPs possess strong absorbance in nearinfrared (NIR) region, and high photothermal conversion efficiency for outstanding photothermal therapy applications. A bimodal drug release triggered by proteinase or NIR irradiation has been revealed, resulting in a significant chemotherapeutic effect in tumor sites because of the preferential drug accumulation and triggered release. Importantly, the in vitro and in vivo experiments demonstrated that DOX@GNR/PSS/HSA NPs, which combined photothermal and chemotherapy for cancer therapy, revealing a remarkably superior synergistic anticancer effect over either monotherapy. All these results suggested a considerable potential of DOX@GNR/PSS/HSA NPs nano-platform for antitumor therapy.

Antithyroid drug regimens before and after 131I-therapy for hyperthyroidism: evidence-based?

Science.gov (United States)

Mijnhout, G S; Franken, A A M

2008-06-01

In view of the new national guideline on thyroid dysfunction, the evidence base for current practice as well as the new guideline is assessed with regard to the use of antithyroid drugs (ATDs) before and after radioiodine (131I) therapy. In December 2006, we surveyed 16 hospitals by telephone about different aspects of their antithyroid drug regimen: all eight academic centres and eight nonacademic teaching hospitals. The literature was searched for an evidence-based answer to each question in the inquiry. 13 of 16 hospitals (81%) use antithyroid drugs for pretreatment before 131I. ATDs are discontinued on average four days before 131I or diagnostic scan. However, 27% stop only three days beforehand, which may diminish the effect of 131I. Propylthiouracil (PTU) is also withdrawn four days before 131I, although the literature shows that PTU diminishes the effect of 131I even if it is stopped 15 days beforehand. Resumption of ATDs after 131I to prevent thyrotoxicosis is common practice (81%). One hospital (6%) never restarts ATDs, two (13%) only by indication. Adjunctive treatment consists of combination therapy in 93%, is usually resumed within two days after 131I therapy, and then continued for two to six months. Routine adjunctive treatment is not evidence-based and may be limited to a high-risk subset, especially elderly patients (>70 years) and patients with cardiac comorbidity. Resumption of ATDs within five to seven days after 131I may diminish the effect of 131I. Antithyroid drug regimens in the Netherlands are heterogeneous. The evidence base of current practice and the new guideline are discussed.

Colchicine in therapy. State of the art and new perspectives for an old drug.

Science.gov (United States)

Famaey, J P

1988-01-01

Colchicine is the most specific treatment in acute gouty attacks. In several European countries, oral colchicine is still used for routine treatment of acute gout. Its selectivity is used as a diagnostic tool. It is also active in the treatment of acute crises of chondrocalcinosis and more occasionally of other arthritic crises (e.g. sarcoidosis). Colchicine appears to be the necessary adjuvant prophylactic drug when starting a hypouricemic treatment with uricosuric or uricolytic drugs for avoiding acute gouty crisis due to sudden mobilisation of the uric acid pool. Besides gout, colchicine is the drug of choice for treating familial mediterranean fever. It appears to be helpful in the treatment of Behçet's disease. It seems also useful for treating fibrosing conditions such as liver cirrhosis and scleroderma. As an adjuvant therapy, it helps treating dermatological disorders which are associated with leucocyte migration as an essential pathogenic factor (e.g. psoriasis, dermatitis herpetiformis, necrotising vasculitis ...). It has been advocated as an adjuvant therapy in malignant diseases as a support in radiotherapy and as an useful drug in various other diseases where it has been tried occasionally (e.g. Paget's disease of the bone, idiopathic thrombocytopenic purpura, disc syndrome). This very old drug remains a modern therapeutic agent.

Automated Detection of Epileptic Biomarkers in Resting-State Interictal MEG Data

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Miguel C. Soriano

2017-06-01

Full Text Available Certain differences between brain networks of healthy and epilectic subjects have been reported even during the interictal activity, in which no epileptic seizures occur. Here, magnetoencephalography (MEG data recorded in the resting state is used to discriminate between healthy subjects and patients with either idiopathic generalized epilepsy or frontal focal epilepsy. Signal features extracted from interictal periods without any epileptiform activity are used to train a machine learning algorithm to draw a diagnosis. This is potentially relevant to patients without frequent or easily detectable spikes. To analyze the data, we use an up-to-date machine learning algorithm and explore the benefits of including different features obtained from the MEG data as inputs to the algorithm. We find that the relative power spectral density of the MEG time-series is sufficient to distinguish between healthy and epileptic subjects with a high prediction accuracy. We also find that a combination of features such as the phase-locked value and the relative power spectral density allow to discriminate generalized and focal epilepsy, when these features are calculated over a filtered version of the signals in certain frequency bands. Machine learning algorithms are currently being applied to the analysis and classification of brain signals. It is, however, less evident to identify the proper features of these signals that are prone to be used in such machine learning algorithms. Here, we evaluate the influence of the input feature selection on a clinical scenario to distinguish between healthy and epileptic subjects. Our results indicate that such distinction is possible with a high accuracy (86%, allowing the discrimination between idiopathic generalized and frontal focal epilepsy types.

Moving forward in uveitis therapy: preclinical to phase II clinical trial drug development.

Science.gov (United States)

Salazar-Méndez, Raquel; Yilmaz, Taygan; Cordero-Coma, Miguel

2016-01-01

Several advances have been made in the diagnostic approach and therapeutic management of patients with immune-mediated uveitis over the last few decades, which have to lead to an improvement in the visual prognosis of patients. However, the use of available therapies, including steroids and immunosuppressive drugs, is still associated with limited efficacy and potentially serious side effects. Consequently, efforts have been made to develop novel therapeutic alternatives including new molecules and innovative therapeutic approaches. Herein, the authors provide an updated review of those drugs in the initial phases of evaluation for the treatment of immune-mediated uveitides as well as the latest evidence from basic research. Enhanced understanding of the pathogenic mechanisms leading to immune-mediated uveitis has led to the identification of new therapeutic targets and thus to the development of more specific drugs. In addition, considering that the eye is a semi-enclosed chamber and that local therapy has the benefit of sparing the rest of the body from potentially toxic exposure, several attempts of establishing direct ophthalmologic avenues for delivery of the established and emerging drugs have also been made. All these advances have been an unquestionable step forward in the challenging management of uveitis patients.

Plasticity of Hippocampal Excitatory-Inhibitory Balance: Missing the Synaptic Control in the Epileptic Brain

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Christian Bonansco

2016-01-01

Full Text Available Synaptic plasticity is the capacity generated by experience to modify the neural function and, thereby, adapt our behaviour. Long-term plasticity of glutamatergic and GABAergic transmission occurs in a concerted manner, finely adjusting the excitatory-inhibitory (E/I balance. Imbalances of E/I function are related to several neurological diseases including epilepsy. Several evidences have demonstrated that astrocytes are able to control the synaptic plasticity, with astrocytes being active partners in synaptic physiology and E/I balance. Here, we revise molecular evidences showing the epileptic stage as an abnormal form of long-term brain plasticity and propose the possible participation of astrocytes to the abnormal increase of glutamatergic and decrease of GABAergic neurotransmission in epileptic networks.

Functional Family Therapy for Young People in Treatment for Nonopioid Drug Use: A Systematic Review

Science.gov (United States)

Filges, Trine; Andersen, Ditte; Jørgensen, Anne-Marie Klint

2018-01-01

Objectives: This review evaluates the evidence on the effects of functional family therapy (FFT) on drug abuse reduction for young people in treatment for nonopioid drug use. Data and Analysis: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized trials. Results: The search yielded two…

Vibrio cholerae infection, novel drug targets and phage therapy.

Science.gov (United States)

Fazil, Mobashar Hussain Urf Turabe; Singh, Durg V

2011-10-01

Vibrio cholerae is the causative agent of the diarrheal disease cholera. Although antibiotic therapy shortens the duration of diarrhea, excessive use has contributed to the emergence of antibiotic resistance in V. cholerae. Mobile genetic elements have been shown to be largely responsible for the shift of drug resistance genes in bacteria, including some V. cholerae strains. Quorum sensing communication systems are used for interaction among bacteria and for sensing environmental signals. Sequence analysis of the ctxB gene of toxigenic V. cholerae strains demonstrated its presence in multiple cholera toxin genotypes. Moreover, bacteriophage that lyse the bacterium have been reported to modulate epidemics by decreasing the required infectious dose of the bacterium. In this article, we will briefly discuss the disease, its clinical manifestation, antimicrobial resistance and the novel approaches to locate drug targets to treat cholera.

The Impact of Herbal Drug Use on Adverse Drug Reaction Profiles of Patients on Antiretroviral Therapy in Zimbabwe

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Tinashe Mudzviti

2012-01-01

Full Text Available Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART. Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record. Results. The majority (98.2% of participants were using at least one herbal drug together with ART. The most common herbal remedies used were Allium Sativum (72.7%, Bidens pilosa (66.0%, Eucalyptus globulus (52.3%, Moringa oleifera (44.1%, Lippia javanica (36.3%, and Peltoforum africanum (34.3%. Two indigenous herbs, Musakavakadzi (OR=0.25; 95% CI 0.076–0.828 and Peltoforum africanum (OR=0.495; 95% CI 0.292–0.839 reduced the occurrence of adverse drug events. Conclusions. The use of herbal drugs is high in the HIV-infected population and there is need for pharmacovigilance programs to recognize the role they play in altering ADR profiles.

Network dynamics in the healthy and epileptic developing brain

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Richard Rosch

2018-03-01

Full Text Available Electroencephalography (EEG allows recording of cortical activity at high temporal resolution. EEG recordings can be summarized along different dimensions using network-level quantitative measures, such as channel-to-channel correlation, or band power distributions across channels. These reveal network patterns that unfold over a range of different timescales and can be tracked dynamically. Here we describe the dynamics of network state transitions in EEG recordings of spontaneous brain activity in normally developing infants and infants with severe early infantile epileptic encephalopathies (n = 8, age: 1–8 months. We describe differences in measures of EEG dynamics derived from band power, and correlation-based summaries of network-wide brain activity. We further show that EEGs from different patient groups and controls may be distinguishable on a small set of the novel quantitative measures introduced here, which describe dynamic network state switching. Quantitative measures related to the sharpness of switching from one correlation pattern to another show the largest differences between groups. These findings reveal that the early epileptic encephalopathies are associated with characteristic dynamic features at the network level. Quantitative network-based analyses like the one presented here may in the future inform the clinical use of quantitative EEG for diagnosis.

Geriatric drug therapy and healthcare utilization in the United kingdom.

Science.gov (United States)

Kennerfalk, Anita; Ruigómez, Ana; Wallander, Mari-Ann; Wilhelmsen, Lars; Johansson, Saga

2002-05-01

To describe the use of prescription drug therapy, especially polypharmacy, in an elderly general population; to relate that use to age, gender, and different types of healthcare utilization; and to investigate the influence of selection of different time windows on the result of the quantity as well as the categories of drugs used. Data on a sample of 5000 patients aged 65-90 years in 1996 were derived from the General Practice Research Database (GPRD). The population covered by GPRD is broadly representative of the UK population treated in general practice. Drug use was assessed using 2 time windows - current use of individual drugs on a random day (index date) and 1 month following the index date. Healthcare utilization was analyzed by use of information on visits to general practitioners (GPs), hospitalizations, and referrals to specialists. Women used more drugs than men; however, the prevalence of polypharmacy, defined as concomitant use of > or =5 drugs, was similar in both genders. The most frequently used therapeutic groups were cardiovascular, central nervous, and gastrointestinal system drugs. Almost 80% of both women and men visited a GP at least once a year. Overall, women used more ambulatory care services and men were hospitalized more often. Use of random date compared with 1-month period resulted in a significant underestimation of the amount of drugs used for acute conditions and, consequently, the risk of polypharmacy. The overall results confirm the findings in earlier studies suggesting that the GPRD might be a useful tool in further studies on prescription drug use among elderly persons. More information on the appropriateness of drug use is needed to prevent overuse as well as underuse of medications among the elderly.

Patterns of muscle activation during generalized tonic and tonic–clonic epileptic seizures

DEFF Research Database (Denmark)

Conradsen, Isa; Wolf, Peter; Sams, Thomas

2011-01-01

Purpose: Tonic seizures and the tonic phase of tonic–clonic epileptic seizures are defined as “sustained tonic” muscle contraction lasting a few seconds to minutes. Visual inspection of the surface electromyogram (EMG) during seizures contributed considerably to a better understanding and accurat...

77 FR 75177 - Impact of Approved Drug Labeling on Chronic Opioid Therapy; Public Hearing; Request for Comments

Science.gov (United States)

2012-12-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1172] Impact of Approved Drug Labeling on Chronic Opioid Therapy; Public Hearing; Request for Comments AGENCY... impact the entire class of opioid drugs or a large subcategory thereof (e.g., ER/LA opioids), such as the...

CYP3A5 Polymorphism In Serbian Paediatric Epileptic Patients On Carbamazepine Treatment

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Milovanovic Dragana Dragas

2015-06-01

Full Text Available Carbamazepine exhibits significant inter-individual variability in its efficacy and safety, which leads to unpredictable therapy outcomes for the majority of patients. Although its complex biotransformation depends on CYP3A5 activity, evidence of association between carbamazepine treatment outcomes and CYP3A5 functional variations remains inconclusive. The aim of the present study was to investigate the distribution of two of the functionally important CYP3A5 variants *2 and *3 as well as their effects on carbamazepine dose requirements, plasma concentrations and clearance in a Serbian population. The study involved 40 paediatric epileptic patients on steady-state carbamazepine treatment. Genotyping was conducted using the PCR-RFLP method, and carbamazepine plasma concentrations were determined using the HPLC method. CYP3A5*2 and *3 polymorphisms were found at frequencies of 0.0% and 97.5%, respectively, which corresponds well to previously published data for Caucasians. No differences in CYP3A5*3 allele frequencies were detected among epileptic patients in comparison to healthy volunteers within similar ethnic populations (p>0.08, indicating that CYP3A5 polymorphism does not represent a risk factor for epilepsy development. There was an observed tendency towards lower dosage requirements (mean±SD: 15.06±4.45 mg/kg vs. 18.74±5.55 mg/kg; p=0.26, higher plasma concentrations (mean±SD: 0.45±0.13 mg/kg vs. 0.38±0.03 mg/kg; p=0.47 and lower clearance (mean±SD: 0.14±0.05 mg/kg vs. 0.15±0.01 mg/kg; p=0.79 of carbamazepine in homozygous carriers of CYP3A5*3/*3 compared to heterozygous CYP3A5*1A/*3 Serbians. Because these genotype groups did not differ significantly in terms of their carbamazepine pharmacokinetics parameters, the proposed effects of CYP3A5*3 on carbamazepine metabolism could not be confirmed.

Avaliação pelo P300 de crianças com e sem epilepsia e rendimento escolar Assessment through P300 of epileptic and non-epileptic children and school performance

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JUCELEI F. VISIOLI-MELO

2000-06-01

Full Text Available Dificuldade de aprendizagem é situação comum em crianças com epilepsia. Distúrbios da inteligência têm sido associados com epilepsia. O potencial cognitivo (P300 é um adjunto clínico para mensurar neurofisiologicamente o processo cognitivo. Foram estudadas 99 crianças com 10 anos a 11 anos e 11 meses. Do Grupo I, sem epilepsia, faziam parte 64 crianças, das quais 32 com bom rendimento e outras 32 com mau rendimento escolar. Do Grupo II, com epilepsia, faziam parte 35 crianças, sendo 21 com bom rendimento escolar e 15 com mau rendimento escolar. Não foi encontrada diferença significativa na latência do P300 entre os dois grupos. Quando foram estratificados segundo o desempenho escolar, as crianças do Grupo I, com bom rendimento escolar, apresentaram latência do P300 de 336 ms e as com mau rendimento escolar, latência de 382 ms; as crianças do Grupo II, com bom rendimento escolar, apresentaram latência do P300 de 363 ms e as com mau rendimento escolar, latência de 400 ms, com diferença significativa. Essa diferença estava localizada entre as crianças não epilépticas com bom desempenho escolar e as com mau desempenho escolar, epilépticas ou não.Learning disability is common in epileptic children. Epilepsy has been associated with disorders of intelligence. Cognitive potential (P300 is considered to be a clinical aid in the neurophysiological measurement of the cognitive process. Ninety-nine children between the ages of 10 years and 11 years and 11 months formed our sample, with good and poor school performance. Group I, non-epileptic, had 64 children of whom 32 had good and 32 poor school performance. Group II, epileptic, had 35 children, of whom 21 had good and 15 poor school performance. No significant difference in P300 latency was found between Groups I and II. When groups were stratified based on school performance, Group I children with good school performance had P300 latency of 336 ms, while the ones with poor

Biological in situ Dose Painting for Image-Guided Radiation Therapy Using Drug-Loaded Implantable Devices

International Nuclear Information System (INIS)

Cormack, Robert A.; Sridhar, Srinivas; Suh, W. Warren; D'Amico, Anthony V.; Makrigiorgos, G. Mike

2010-01-01

Purpose: Implantable devices routinely used for increasing spatial accuracy in modern image-guided radiation treatments (IGRT), such as fiducials or brachytherapy spacers, encompass the potential for in situ release of biologically active drugs, providing an opportunity to enhance the therapeutic ratio. We model this new approach for two types of treatment. Methods and Materials: Radiopaque fiducials used in IGRT, or prostate brachytherapy spacers ('eluters'), were assumed to be loaded with radiosensitizer for in situ drug slow release. An analytic function describing the concentration of radiosensitizer versus distance from eluters, depending on diffusion-elimination properties of the drug in tissue, was developed. Tumor coverage by the drug was modeled for tumors typical of lung stereotactic body radiation therapy treatments for various eluter dimensions and drug properties. Six prostate 125 I brachytherapy cases were analyzed by assuming implantation of drug-loaded spacers. Radiosensitizer-induced subvolume boost was simulated from which biologically effective doses for typical radiosensitizers were calculated in one example. Results: Drug distributions from three-dimensional arrangements of drug eluters versus eluter size and drug properties were tabulated. Four radiosensitizer-loaded fiducials provide adequate radiosensitization for ∼4-cm-diameter lung tumors, thus potentially boosting biologically equivalent doses in centrally located stereotactic body treated lesions. Similarly, multiple drug-loaded spacers provide prostate brachytherapy with flexible shaping of 'biologically equivalent doses' to fit requirements difficult to meet by using radiation alone, e.g., boosting a high-risk region juxtaposed to the urethra while respecting normal tissue tolerance of both the urethra and the rectum. Conclusions: Drug loading of implantable devices routinely used in IGRT provides new opportunities for therapy modulation via biological in situ dose painting.

[Clinical and electrophysiologic studies on epileptic negative myoclonus in atypical benign partial epilepsy of childhood].

Science.gov (United States)

Yang, Zhi-xian; Liu, Xiao-yan; Qin, Jiong; Zhang, Yue-hua; Bao, Xin-hua; Chang, Xing-zhi; Wu, Ye; Xiong, Hui

2008-12-01

To investigate the clinical, neurophysiologic characteristics and therapeutic considerations of epileptic negative myoclonus (ENM) in atypical benign partial epilepsy of childhood (ABPE). Video-EEG monitoring with outstretched arm tests were carried out in 17 patients, and 9 of them were examined with simultaneous electromyography (EMG). The ENM manifestations, electrophysiologic features and responses to antiepileptic drugs (AED) were analyzed. Seventeen patients were diagnosed as having benign childhood epilepsy with centrotemporal spikes (BECT) during the early course of the disease and were treated with AED. During the course of the disease, hand trembling, objects dropping, head nodding and instability during standing might be clues for ENM occurrence. ENM had been confirmed in our patients by outstretched arm tests during video-EEG recording. The ictal EEG showed that high-amplitude spikes followed by a slow wave over the contralateral motor areas. This was further confirmed by time-locked silent EMG in 9 patients. During ENM occurrence or recurrence, the habitual seizures and interictal discharges were exaggerated. Atypical absence seizures also occurred in 6 patients. The alteration of therapeutic options of AED relating to ENM appearance in some patients included the add-on therapy with carbamazepine (CBZ), oxcarbazepine, phenobarbital, or withdrawal of valproate (VPA). ENM was controlled in most cases by using VPA, clonazepam (CZP) and corticosteroid with different combination. ENM could occur during the course of ABPE. Outstretching arm tests during video-EEG monitoring in combination with EMG was essential to confirm ENM. The ENM occurrence was always associated with the frequency increasing of habitual seizures and the aggravation of interictal discharges. Some AED such as CBZ might induce ENM. VPA, benzodiazepines and corticosteroid with different combination were relatively effective in treatment of ENM.

[Experimental therapy of cardiac remodeling with quercetin-containing drugs].

Science.gov (United States)

Kuzmenko, M A; Pavlyuchenko, V B; Tumanovskaya, L V; Dosenko, V E; Moybenko, A A

2013-01-01

It was shown that continuous beta-adrenergic hyperstimulation resulted in cardiac function disturbances and fibrosis of cardiac tissue. Treatment with quercetin-containing drugs, particularly, water-soluble corvitin and tableted quertin exerted favourable effect on cardiac hemodynamics, normalized systolic and diastolic function in cardiac remodeling, induced by sustained beta-adrenergic stimulation. It was estimated that conducted experimental therapy limited cardiac fibrosis area almost three-fold, that could be associated with first and foremost improved cardiac distensibility, characteristics of diastolic and also pump function in cardiac remodeling.

Cost-effectiveness-analysis: radioiodine or antithyroid drugs as first-line therapy of hyperthyroidism due to Graves' disease

International Nuclear Information System (INIS)

Dietlein, M.; Moka, D.; Dederichs, B.; Schicha, H.; Hunsche, E.; Lauterbach, K.W.

1999-01-01

Aim: As first-line therapy of hyperthyroidism caused by Graves' disease antithyroid drugs are favoured in Europe, while radioiodine therapy is favoured in the USA. Radioiodine therapy has become more economic in Germany since the new recommendations by the Federal German Radiation Protection Committee (SSK) for patient discharge guidelines. Method: Sensitivity analyses took into account the long-term relapse rate of conservative or radioiodine therapy, use of diagnostic tests, level of health insurance, drops in productivity and a discount factor. Costing models included the costs of follow-up care over 30 years. The costs of the hospitalisation for radioiodine therapy were calculated for 300 patients, discharged with 250 MBq I-131 residual activity. Result: Antithyroid drugs were considered cost-effective when they achieved relapse rate of 50% or less, a cut in the number of tests needed and reduced working hours. Failure to meet any one of these conditions makes primary radioiodine therapy more cost-effective in 1593 of 1944 calculated costing models. Repeated conservative therapies will increase clearly the overall costs. Conclusion: Radioiodine is a cost-effective, first-line therapy in patients with a special risk of relapse after primary conservative therapy (goitre, younger patient, persistent elevated TSH-receptor-antibodies or Tc-uptake). (orig.) [de

A combination therapy of selective intraarterial anti-cancer drug infusion and radiation therapy for muscle-invasive bladder cancer

International Nuclear Information System (INIS)

Okuno, Yumiko; Zaitsu, Masayoshi; Mikami, Koji; Takeuchi, Takumi; Matsuda, Izuru; Arahira, Satoko

2017-01-01

The gold standard for the treatment of muscle-invasive bladder cancer Without metastasis is radical cystectomy. However, there increase patients very elderly and with serious complications. They are not good candidates for invasive surgical operation. Intraarterial infusion of 70 mg/m"2 of cisplatin and 30 mg/m"2 of pirarubicin into bilateral bladder arteries was conducted for 5 patients diagnosed with muscle invasive bladder cancers without distant metastasis. Right and left distribution of anti-cancer drugs was determined based on the location of bladder tumor(s). External beam radiation therapy was commenced immediately following intraarterial infusion. The patients were followed up with clinical and radiographic investigations and bladderbiopsy was performed as needed. Patients were all males who are smoking or with smoking history ranging from 73 to 85 years of age (median 82). The duration between transurethral resection of bladder tumors (TUR-Bt) and intraarterial infusion of anti-cancer drugs was 47.4 days (range 26-68), the median follow-up period after intraarterial infusion was 21.5 months (range 87-547) without death. Total radiation dose was 59.2 ±3.0 Gy. Complete remission was accomplished in all cases. One patient showed intravesical recurrence of non muscle-invasive tumors 45.8 months following intraarterial infusion and underwent TUR-Bt. Two cases underwent bladder biopsies showing no tumors. All patients but one case with bladder recurrence were free of tumor recurrence with radiographic investigation. For adverse events, acute renal failure was in one case and leukocytopenia was in all 5 cases, Grade 2 for one and Grade 3 for 4 cases. Follow-up periods are not long enough, but early results of a combination therapy of selective intraarterial anti-cancer drug infusion and radiation therapy for muscle-invasive bladder cancer were good. (author)

Differential effects of valproic acid and enzyme-inducing anticonvulsants on nimodipine pharmacokinetics in epileptic patients

Science.gov (United States)

Tartara, A.; Galimberti, C.A.; Manni, R.; Parietti, L.; Zucca, C.; Baasch, H.; Caresia, L.; Mück, W.; Barzaghi, N.; Gatti, G.; Perucca, E.

1991-01-01

1 The single dose pharmacokinetics of orally administered nimodipine (60 mg) were investigated in normal subjects and in two groups of epileptic patients receiving chronic treatment with hepatic microsomal enzyme-inducing anticonvulsants (carbamazepine, phenobarbitone or phenytoin) and sodium valproate, respectively. 2 Compared with the values found in the control group, mean areas under the plasma nimodipine concentration curve were lowered by about seven-fold (P anticonvulsants and increased by about 50% (P < 0.05) in patients taking sodium valproate. 3 Nimodipine half-lives were shorter in enzyme-induced patients than in controls (3.9 ± 2.0 h vs 9.1 ± 3.4 h, means ± s.d., P < 0.01), but this difference could be artifactual since in the patients drug concentrations declined rapidly below the limit of assay, thus preventing identification of a possible slower terminal phase. In valproate-treated patients, half-lives (8.2 ± 1.8 h) were similar to those found in controls. PMID:1777370