[Which factors have an impact on levetiracetam serum concentrations? An analysis in 163 patients with epilepsy]. / Welche Faktoren beeinflussen die Serumkonzentration von Levetiracetam? Eine Analyse bei 163 Patienten mit Epilepsie.

We evaluated factors possibly influencing serum concentrations of levetiracetam (LEV-SC). The study included 163 patients with epilepsy (91 men, 72 women; mean age 39.6 years). The duration of treatment on first analysis was 226 days; the mean daily dose amounted to 2,434 mg. In each patient between one and seven measurements were carried out (mean 2.2). LEV-SC significantly depended on daily dosage and the interval between the time the medication was taken and the time of blood extraction. A marked drop in LEV-SC was observed 4-5 h following ingestion. Carbamazepine, oxcarbazepine and clobazam reduced LEV-SC, whereas valproate elevated LEV-SC significantly. When assessing evaluation of compliance these factors have to be taken into consideration when comparing intraindividual LEV-SC.

Right ventricular dysfunction and the incidence of implantable cardioverter-defibrillator therapies.

INTRODUCTION: Implantable cardioverter-defibrillator (ICD) therapy is well established in preventing sudden cardiac death in patients with left ventricular dysfunction. The influence of right ventricular (RV) function on ICD therapy for sudden cardiac death (SCD) is not known. METHODS: We retrospectively studied 222 patients receiving an ICD for primary prevention of SCD. Baseline clinical and echocardiographic data were gathered. RV systolic function was qualitatively assessed as normal or abnormal (described as mildly, moderately, or severely reduced). Primary endpoint was combined ICD therapy or death and secondary endpoint was ICD therapy alone. RESULTS: The mean follow-up was 940 +/- 522 days. The mean left ventricular ejection fraction was 0.23 +/- 0.07. By Kaplan-Meier analysis, RV dysfunction was predictive of combined ICD therapy or death when comparing between normal and abnormal RV function (P = 0.008) and among qualitative ranges of RV function (P = 0.012). RV dysfunction was not predictive of ICD therapy alone with either type of classification. After adjusting for clinical covariates, severe RV dysfunction was predictive of the combined endpoint of ICD therapy or death (HR 2.02, 95% CI 1.04-3.92, P = 0.037). CONCLUSION: Severe RV dysfunction appears to be an independent predictor of the combined endpoint of ICD therapy or death. RV dysfunction does not reliably predict the incidence of ICD therapy alone.

Which patients become seizure free with antiepileptic drugs? An observational study in 821 patients with epilepsy.

OBJECTIVES: Analysis of factors influencing seizure outcome in antiepileptic drug treatment of epilepsy. PATIENTS AND METHODS: Retrospective analysis of 500 patients with complete seizure control and 321 patients with refractory epilepsy (mean ages 33.3 and 32.1 years respectively). RESULTS: The seizure-free group consisted of 377 patients with symptomatic/cryptogenic epilepsy (SCE; mean seizure control 45 months) and 123 patients with idiopathic generalized epilepsy (IGE; mean seizure control 61 months) (P = 0.02). Of the patients with SCE, 35.7% had achieved seizure control with monotherapy (MT), 29.6% with >or=2 AEDs. No single AED was superior in MT. Of the patients with IGE, 35.9% had become seizure free with MT, 15.6% on combination therapy (CT). Valproate MT was more commonly associated with seizure freedom than lamotrigine (P < 0.05). CONCLUSIONS: The results indicate that, in SCE, seizures can be controlled with carefully selected CT more commonly than suggested by previous studies. The seizure prognosis of patients with IGE presenting to a specialist in epilepsy may be worse than previously thought.

Course of chronic focal epilepsy resistant to anticonvulsant treatment.

Sixty-three patients (32 women, 31 men), chronically treated with carbamazepine, phenytoin, valproate and/or phenobarbital, were investigated. Mean age at manifestation of epilepsy was 16.4 years; mean age at onset of documentation of seizure frequency was 33.7 years; mean duration of follow-up was 104.8 months; mean number of documented seizures per patient was 313.2. A statistical analysis of seizure diaries was performed. For each day the entries were the number of seizures per day. Linear trends, the amount of variance of the seizure frequency compared to randomly distributed events, were computed with the resulting coefficients fitting a general linear regression model. Non-random aggregations (clusters) were searched for as well as gaps of seizure manifestation. A similar number of patients exhibited a decrease (30%) or increase (29%) of seizure frequency during the course of epilepsy. The variance of the daily seizure frequency was in most patients (78%) significantly higher or lower (5%) than corresponding random distributions. The coupling coefficient to the day before was significantly larger than zero (indicating seizure clustering) in 57% of patients. Significant rhythmic components in seizure profiles (quasi-weekly or quasi-monthly) were found in 31 patients (both male and female). Periods of increased seizure frequency (clusters) manifested in 62% of patients; seizure gaps of at least 1 year occurred in 29 patients followed by seizure relapses in 20 patients. In conclusion, there is no evidence for a unique type of course in chronic focal epilepsy in patients on antiepileptic drugs.

Report on the Development of the Advanced Encryption Standard (AES).

In 1997, the National Institute of Standards and Technology (NIST) initiated a process to select a symmetric-key encryption algorithm to be used to protect sensitive (unclassified) Federal information in furtherance of NIST's statutory responsibilities. In 1998, NIST announced the acceptance of 15 candidate algorithms and requested the assistance of the cryptographic research community in analyzing the candidates. This analysis included an initial examination of the security and efficiency characteristics for each algorithm. NIST reviewed the results of this preliminary research and selected MARS, RC™, Rijndael, Serpent and Twofish as finalists. Having reviewed further public analysis of the finalists, NIST has decided to propose Rijndael as the Advanced Encryption Standard (AES). The research results and rationale for this selection are documented in this report.

Precipitating factors and therapeutic outcome in epilepsy with generalized tonic-clonic seizures.

OBJECTIVES: The aim of the study was to evaluate the influence of precipitating factors and therapy on the outcome of epilepsy with generalized tonic-clonic seizures. PATIENTS AND METHODS: Retrospective analysis of data from 34 patients (mean age at seizure onset 19 years; mean duration of follow-up 9.2 years) suffering from epilepsy of either cryptogenic or remote symptomatic (n = 19), or idiopathic (n = 15) etiology. The total number of seizures in all patients was 146. RESULTS: Without treatment 97 seizures manifested during 90.5 years without treatment (1.07 seizures/year), during treatment with carbamazepine or valproate 49 seizures occurred within 224 years (0.2 seizures/year). The frequency of seizures was significantly lower during treatment. Precipitating factors were found in relation to 31% of seizures in patients with remote symptomatic or cryptogenic epilepsy, and for 51% of seizures in patients with idiopathic epilepsy. CONCLUSIONS: There was a low frequency of seizures in patients with generalized tonic-clonic seizures. Precipitating factors are common. Antiepileptic drug treatment is effective.

Advances in telecommunications concerning epilepsy.

Telemedicine is a rapidly expanding discipline. Looking back on a long tradition of telemetric measurement and transmission of brain electrical data, one might ask how relevant telecommunication techniques have become for clinical work in epileptology. In principle, communication can be either between patient and doctor or between doctor and doctor. The former includes telephone reports on frequency and severity of seizures and on mental and physical state. Because of the special problems of patients with epilepsy, the need for traveling should be minimized. To maintain close contact, telemetric transmission of electroencephalograms (EEG), seizure video-registration, and monitoring of anti-epileptic drug (AED) blood levels from home are desirable, but the technical tools now available are not of sufficiently high performance for these applications. However, physicians and medical units can communicate using high-rate data transfer. There are major problems with this technology. Transfer rates using the internet are not fixed. Moreover, using six digital telephone lines simultaneously, good-quality transmission of a 3-min video may take more than 1 h, restricting interactivity. In contrast to imaging (e.g., magnetic resonance imaging), there is no generally accepted protocol for handling EEG/electrocorticography data. There are also legal problems relating to the responsibility for failures and safety of personal or medical data. Nevertheless, the expenses of installation and use of such equipment appear justified by the expected benefits, for the patients (avoiding travel and multiple investigations, checking diagnosis and therapy, amending quality of life), for the physician (sparing equipment and manpower, accelerating and improving diagnosis), for the epilepsy center (increased database for expert systems, improved logistic and data storage) and, finally, for insurance providers (reduced overall costs). When the neurosurgical procedure is remote from the place of presurgical evaluation, telecommunication should be obligatory.

Zoonotic Onchocerca (Nematoda:Filarioidea) in the cornea of a Colorado resident.

OBJECTIVE: A female patient, resident in the state of Colorado, presented with iritis of the right eye. Slit-lamp examination showed the presence of a thin, threadlike worm entwined in the cornea. The patient was taken to surgery for removal of the parasite. DESIGN: A case report. INTERVENTION: A 3-mm-long supertemporal incision was made in the cornea and further dissected until the worm could be grasped and removed by gentle traction. RESULTS: The worm, a filarial nematode, was identified as a member of the genus Onchocerca, most likely Onchocerca cervicalis, a natural parasite of horses. The patient had an uneventful recovery, and 1 week after surgery, her visual acuity, intraocular pressure, and corneal edema were all resolving. CONCLUSION: In the United States and elsewhere, most cases of zoonotic filarial infection involving the eye are caused by Dirofilaria or Dipetalonema-like worms. However, the current case was caused by a species of Onchocerca. This is the first case of zoonotic Onchocerca from the eye to be reported, only the second case of zoonotic Onchocerca in the United States, and the seventh case worldwide. The worm was removed surgically, and the patient had an uneventful recovery.

Seizure occurrence during ovulatory and anovulatory cycles in patients with temporal lobe epilepsy: a prospective study.

We investigated the influence of ovulatory and anovulatory menstrual cycles on seizure occurrence in female patients with complex partial seizures. We prospectively documented seizures in relation to menstrual cycles (defined by measurement of basal body temperature and progesterone serum concentrations) in 39 female patients. One hundred and thirty-two cycles of 35 patients entered final analysis. Only eight patients had anovulatory cycles, in 18 patients all cycles were ovulatory. In the remaining nine patients anovulatory as well as ovulatory cycles were documented. In ovulatory cycles the mean frequency of seizures during the days of menstruation was significantly higher as compared to the periovulatory or the luteal phase of the cycles. During anovulatory cycles seizure frequency was significantly lower during menstruation than in the remaining days of the cycles. Since progesterone is known to exhibit anticonvulsant effects, seizure occurrence during menstruation seems to be related to ovulatory cycles, possibly due to the premenstrual decrease of progesterone. Therapeutic recommendations for the treatment of seizures related to the menstrual cycle (catamenial seizures) include the administration of hormones, as progesterone (recommended especially for women with catamenial epilepsy who have a documented inadequate luteal phase) or the suppression of the menstrual hormonal cycle by synthetic gonadotropin releasing hormone analogs.

Possibilities and limitations of magnetic source imaging of methohexital-induced epileptiform patterns in temporal lobe epilepsy patients.

The usefulness of MEG-based techniques in lateralizing and localizing the epileptogenic area was investigated in the present study. Spontaneous and methohexital-induced spikes were studied in a group of 15 patients with temporomesial epilepsy using a 37-channel neuromagnetometer. The accuracy of the magnetic source imaging was compared to the results of electrocorticographic (ECoG) recordings. Differences of drug-induced spike densities in the MEG recordings between both sides confirmed a similar lateralizing power of the MEG and ECoG recordings. Source location analyses based on a moving dipole model resp. a rotating dipole model were performed using a spherical head model. After subdivision of the volume of each patient's head, 8 cm3 cubicles containing at least 3 source locations were projected onto the individual MRI scan and resulted in source locations within or close to the presurgically defined primary epileptogenic area only in 3 of the 15 patients. Spike induction by methohexital has the advantage of shortening the recording period as compared to recordings of interictal epileptiform discharges. However, the correlation analyses of spike densities from MEG and ECoG recordings and the source location analyses from MEG recordings indicate that spike generated in deep temporomesial structures may escape the MEG registration.

Subdural electrodes.

Physical aspects favour subdural registrations: as the solid angle under which a source is seen from a nearby electrode, the potential is large; there is no distortion by high impedence between source and electrode, nor by perpendicular short circuits; the frequency response is quasi-linear. Technical aspects and implantation strategy are outlined. Interictal and ictal ECoG patterns of diagnostical relevance and activation procedures are discussed. Advantages of subdural electrodes are: They provide detailed information on the epileptogenic zone, data on prognosis, are free of artefacts, allow electrical stimulation to determine eloquent cortex areas; by mathematical analysis methods the localizing power is increased. Disadvantages are: closed fields can be missed (recordable only by depth electrodes), in comparison to EEG, costs are considerably higher. Risks are practically absent with strip electrodes. In about half of the investigated patients, subdural electrodes were necessary to minimize the area of resection on a rational basis.

[A brief psychotherapeutic synergistic approach in child and adolescent psychiatry]. / Ein kurztherapeutisch synergetischer Ansatz in der Kinder- und Jugendpsychiatrie.

The controversy between the concepts of family therapy and systemic therapy is one issue to design a synergetic concept of brief therapy in the psychiatric treatment of children and adolescents. Some principles of the radical-constructivism, systemic theory an the psychology of narratives will be discussed and related to concepts of solution-oriented brief therapy. A case example demonstrates the perspectives of this approach in the ambulant psychiatric treatment.

Localization of the epileptic focus during methohexital-induced anesthesia.

A short anesthesia was provided by methohexital for painless percutaneous removal of subdural electrodes in 27 patients with medically intractable, complex partial seizures who had undergone invasive preoperative evaluation. Electrocorticographic(ECoG) recordings performed before and during the narcosis were submitted to visual (n = 27) and computerized (n = 3) analysis to obtain additional information about the location of the epileptic focus (or foci). The following observations were made: focal epileptiform potentials were induced in 24 of 27 patients (89%); (b) in 20 of these 24, the induced spikes appeared amid or were followed by isoelectric or subdelta activity. These spikes were characterized by high amplitude as well as rhythmic and synchronized appearance over a circumscribed focal area (or areas) known to be spontaneously epileptogenic. This phenomenon, termed spike-burst-suppression (SBS) pattern, allowed identification of the primary epileptic focus in many patients with temporal lobe epilepsy. Furthermore, it indicated a good outcome of epilepsy surgery. Computerized analysis of the induced synchronized spikes (n = 3) allowed further delineation of the primary site of epileptogenicity and quantitative comparison of multiple epileptic generators. ECoG recording during deep methohexital-induced narcosis is a valuable tool for lateralization and delineation of the primary epileptogenic focus.

Serum prolactin concentrations and epilepsy. A study which compares healthy subjects with a group of patients in presurgical evaluation and circadian variations with those related to seizures.

In 20 healthy subjects (10 female and 10 male) and 17 patients undergoing presurgical epilepsy evaluation with intracranial EEG electrodes, circadian variations of serum prolactin (PRL) were measured. A comparison between the peak values found in normals with the postictal rises in patients, led us to consider 700 microU/ml to be the threshold of diagnostic value and the observed rises above this level to be all induced by seizures. In order to assess the clinical value of this threshold, PRL was measured postictally in a further 30 patients with epilepsy and in 11 patients with psychogenic seizures. In none of the latter group did PRL rises exceed 700 microU/ml, while they did so in 39% of the complex partial seizures and in 80% of the tonic-clonic seizures. There was no significant difference with respect to sex (a rise over 700 microU/ml in 42% in male and in 55% in female patients). Based on the findings in 17 patients investigated by means of intracranial electrodes, we were not able to establish different criteria for different focus localisations: in 66% of both temporal as well as frontal lobe seizures the 700 microU/ml level was exceeded. As a trend, in the period preceding an epileptic seizure we found a slightly decreasing PRL level, whereas in healthy persons the PRL concentrations gradually increased in the 40 minutes before the maximum spontaneous peak was reached.

Rethinking levels of abstraction in family systems theories.

This article is an attempt to improve the way we conceptualize "levels" in family systems. The first section reframes thinking about levels by identifying an array of different ways of thinking about levels. The next section suggests a parsimonious frame-work for thinking about levels of abstraction in systemic processes. The proposed framework integrates several earlier ways of conceptualizing levels, and helps eliminate some of the confusion, inconsistencies, fragmentation, and limitations of some earlier models. The new framework has three categories that are called Levels I, II, and III. The most abstract level (III) includes phenomena such as family paradigms and values. The intermediate level includes processes such as second-order change, regime, and "meta" processes such as metacommunication and meta-rules. The least abstract level refers to specific processes such as transformation processes and rules. The article concludes with an attempt to demonstrate the usefulness of the proposed framework by showing how it can be used to eliminate a number of conceptual problems in earlier models, improve conceptual clarity, help generate new theoretical insights, and help deal with several controversies in the field.

Elevated plasma adrenocorticotropin (ACTH) with adrenal hyperplasia: a new factor in ACTH regulation?

We report a patient with Cushing's syndrome in whom the etiology of the hypercortisolemia could not be definitely established despite extensive biochemical investigations. Results included raised basal serum cortisol, plasma ACTH, and urinary free cortisol; failure to suppress even a paradoxical rise in serum cortisol after dexamethasone (1 mg overnight, 2, 8, and 16 mg/day); and a definite but not exaggerated rise in 11-deoxycortisol after metyrapone. After iv CRF, plasma ACTH rose from 22 to 30 pmol/L. Abdominal computed tomographic scanning showed adrenal hyperplasia; the presence of an adrenal adenoma, although suspected, was not established. An unusual finding was the presence in the urine of large amounts of 21-deoxycortisol metabolites, including 3 alpha,11 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one and 5 beta-pregnane 3 alpha,11 beta,17 alpha,20 alpha-tetrol. On the basis of preoperative biochemical/radiological findings, a provisional diagnosis of ACTH-dependent Cushing's syndrome associated with autonomous bilateral adrenal hyperplasia was made. Incomplete bilateral adrenalectomy was performed; adrenal hyperplasia was histologically confirmed, but no tumor was found. However, ACTH was measured 1) just before operation when the patient was receiving treatment with metyrapone, and 2) postoperatively when the patient was receiving steroid replacement only, and on these occasions ACTH levels were lower than during the initial investigations. Pituitary scans before and after adrenalectomy were similar, offering no evidence of pituitary infarction. We propose that abnormal production of 21-deoxycortisol contributed to the aberrant regulation of ACTH and cortisol in this case, providing an example of a previously unreported cause of hypercortisolemia.

Current status of bioassay procedures to detect and quantify previous exposures to radioactive materials. Bioassay Procedures Working Group.

This report was prepared by a working group established by the Oak Ridge Associated Universities (ORAU) for the purpose of assessing the current capabilities of bioassay methods that can be used to determine the occurrence and magnitude of a previous internal deposition of one or more radionuclides. The first five sections discuss general features of the use of in-vitro bioassay samples to achieve this purpose. The remainder of the report is focused on the possible use of urine bioassay procedures to detect and quantify internal depositions of radionuclides that may have occurred in United States occupation troops in Hiroshima or Nagasaki, Japan, prior to 1 July 1946, or to personnel who participated in atmospheric nuclear weapons tests conducted between 1945 and 1962. Theoretical calculations were made to estimate the quantities of various radionuclides produced in a 20-kiloton (kt) nuclear detonation that might still be present in measurable quantities in people today if they were exposed 25 to 40 y ago. Two radionuclides that emerged as good choices for this type of bioassay analysis were 90Sr, which emits beta particles, and 239,240Pu, which emits alpha particles. The current status and future prospects of chemical procedures for analyzing in-vitro urine bioassay samples for these two radionuclides were examined to determine the minimum amounts that could be detected with current methods and how much one might expect the sensitivity of detection to improve in the near future. Most routine 239,240Pu bioassay analyses involve detection by alpha spectrometry. The current minimum detectable amount (MDA) is about 0.74 mBq L-1 (20 fCi L-1), but this could be lowered to 74 muBq L-1 (2 fCi L-1). An MDA of 0.74 mBq L-1 (20 fCi L-1) is adequate for routine bioassay analyses but is too high to detect most uptakes of 239,240Pu that may have occurred 25 to 40 y ago. Methods under development that are or can be much more sensitive and have lower MDAs than alpha spectrometry for 239Pu are fission track analysis and mass spectrometry. Currently, the fission track analysis method has an MDA of about 19 muBq L-1), and this may eventually be lowered to 1.9 muBq L-1 (0.005 fCi L-1). The current MDA for 239Pu by mass spectrometry is about 7.4 mBq L-1 (200 fCi L-1), but the potential exists that it could be lowered to a value of about 0.37 muBq L-1 (0.01 fCi L-1).(ABSTRACT TRUNCATED AT 400 WORDS)