bluuebunny/crossref_metadata_2025 huggingface dataset:
Four year clinical statistics of iridium‐192 high dose rate brachytherapy
Authors: SHIGEHARA KAZUYOSHI , MIZOKAMI ATSUSHI , KOMATSU KAZUTO , KOSHIDA KIYOSHI , NAMIKI MIKIO
Published: March 2006

Background:  We evaluated the efficacy and complications of high dose rate (HDR) brachytherapy using iridium‐192 (192Ir) combined with external beam radiotherapy (EBRT) in patients with prostate cancer.

Methods:  Ninety‐seven patients underwent 192Ir HDR brachytherapy combined with EBRT at our institution between February 1999 and December 2003. Of these, 84 patients were analysed in the present study. 192Ir was delivered three times over a period of 2 days, 6 Gy per time, for a total dose of 18 Gy. Interstitial application was followed by EBRT at a dose of 44 Gy. Progression was defined as three consecutive prostate‐specific antigen (PSA) rises after a nadir according to the American Society for Therapeutic Radiology and Oncology criteria. The results were classified into those for all patients and for patients who did not undergo adjuvant hormone therapy.

Results:  The 4‐year overall survival of all patients, the nonadjuvant hormone therapy group (NAHT) and the adjuvant hormone therapy group (AHT) was 87.2%, 100%, and 70.1%, respectively. The PSA progression‐free survival rate of all patients, NAHT, and AHT was 82.6%, 92.0%, and 66.6%, respectively. Of all patients, the 4‐year PSA progression‐free survival rates of PSA < 20 and PSA ≥ 20 groups were 100%, and 46.8%, respectively. According to the T stage classification, PSA progression‐free survival rates of T1c, T2, T3, and T4 were 100%, 82.8%, 100%, and 12.1%, respectively. Prostate‐specific antigen progression‐free survival rates of groups with Gleason scores (GS) < 7 and GS ≥ 7 were 92.8% and 60.1%, respectively. Of NAHT, PSA progression‐free survival of PSA < 20 was 100% vs 46.8% for PSA ≥ 20, that of T1c was 100% vs 75% for T2, and that of GS < 7 was 100% vs 75% for GS ≥ 7. No significant intraoperative or postoperative complications requiring urgent treatment occurred except cerebellum infarction.

Conclusions:  192Ir HDR brachytherapy combined with EBRT was as effective as radical prostatectomy and had few associated complications.
Is chronic inflammatory change in the prostate the major cause of rising serum prostate‐specific antigen in patients with clinical suspicion of prostate cancer?
Authors: CHANG SUNG‐GOO , KIM CHUL‐SOO , JEON SEUNG HYUN , KIM YOUN‐WHA , CHOI BO YOUL
Published: March 2006

Aim:  To evaluate the cause of elevated prostate‐specific antigen (PSA) in patients with transrectal needle biopsy negative for prostate cancer.

Methods:  Serum PSA concentration, prostate volume, and pathologic findings were examined in 223 patients with negative biopsy for prostate cancer. The degree of prostate inflammation was determined by the extent and degree of inflammation shown by biopsy specimens and is expressed as an inflammation score (range: 0–36).

Results:  A significant correlation was found between PSA concentration and prostate total volume (P = 0.0001). Prostate chronic inflammation showed no correlation with PSA concentration (P = 0.485, F = 0.488). After allocating patients to normal PSA (≤4 ng/mL) and high PSA (>4 ng/mL) groups, we found that serum PSA concentrations in both groups were predominantly affected by prostate total volume.

Conclusions:  An increase in prostate volume appears to be the major contributor to a high serum PSA concentration in patients with negative biopsy for prostate cancer. However, in contrast to previous reports, there was no correlation between the degree of prostate chronic inflammation and serum PSA concentrations.
How frequent are invasive therapies required in patients receiving tamsulosin for benign prostatic hyperplasia? A retrospective long‐term study
Authors: KAWABE KAZUKI , HOMMA YUKIO , KUBOTA KIYOSHI , SOZU TAKASHI ,   THE TAMSULOSIN LONG‐TERM STUDY GROUP
Published: March 2006

Abstract  Three hundred Japanese patients with benign prostatic hyperplasia (BPH) who started an α1‐adrenoceptor blocker, tamsulosin, between 1993 and 1996 were followed for 3.0 ± 3.3 years (mean ± SD) to determine whether an association existed between the disease severities measured prior to the tamsulosin treatment and the timing at which the invasive therapy was implemented. Patients with a lower quality of life (QOL) index or maximum urinary flow rate (Qmax) were transferred for invasive therapy earlier than those with less severe BPH. The International Prostate Symptom Score (I‐PSS) was also associated, but apparently to a lesser extent, with the timing of the invasive therapy. Finally, the overall severity evaluated using all of the above three indices, I‐PSS, QOL index, and Qmax, in accordance with the ‘Severity Criteria for BPH’ issued by the Japanese Urological Association, was found to be a good measure for predicting the prognosis of patients with BPH treated with tamsulosin.
Prenatal testicular torsion: Ultrasonographic features, management and histopathological findings
Authors: ARENA FRANCESCO , NICÒTINA PIERO ANTONIO , ROMEO CARMELO , ZIMBARO GIOVANNI , ARENA SALVATORE , ZUCCARELLO BIAGIO , ROMEO GIUSEPPE
Published: March 2006

Aim:  To highlight the ultrasonographic features of prenatal torsion of the testis in utero (IUTT) at presentation, the neonatal management and the histological findings postorchiectomy or biopsy.

Methods:  Seven newborns underwent emergency exploration for IUTT. All patients underwent a sonography and real‐time color Doppler ultrasound study of the scrotum before any surgical procedure. A histological examination was performed in the removed specimens.

Results:  Sonography of the scrotum revealed enlarged, heterogeneous testes. In all cases the color and power Doppler did not reveal any flow signal on the affected side. Four newborn with unilateral testicular torsion underwent orchiectomy and contralateral orchidopexy. In one neonate after detorsion and with the absence of gangrenous changes and a reassuring biopsy, a twisted testis could be treated conservatively with orchidopexy. In another case, the parents, acknowledging the inviability of the affected testis, gave consent only for a biopsy of the testis. In the neonate with bilateral IUTT, bilateral testicular biopsies were performed. Histology of the removed testes variably showed interstitial red cell extravasion and coagulation or hemorrhagic necrosis. Light microscopy of the preserved testis highlighted surviving seminiferous tubules, with gonocytes, spermatogonia and fetal Sertoli cells.

Conclusions:  An early diagnosis and treatment in IUTT is essential. Surgical exploration should be always performed through the inguinal route. In bilateral IUTT testes should be left to try to assure, as long as possible, a residual Leydig cell function.
Cytokeratin‐20 and seminal vesicle secretory protein VI as possible marker proteins in urinary bladder preneoplastic lesions induced by N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine
Authors: KIM HYUNG‐JEE , SOHNG INHO , HWANG CHEOL‐HO , PARK JI‐YOUNG
Published: March 2006

Background:  A simple and non‐invasive methods for the diagnosis of transitional cell carcinoma of the bladder are needed for the prevention of invasive tumor. A proteomic technology has recently been developed to facilitate protein profiling of biological mixtures. We tried to detect the marker proteins by proteomic approach during the initiation stages on N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine (BBN)‐induced bladder carcinogenesis in rats.

Methods:  Ten rats in group A were given 0.05% BBN in drinking water for 12 weeks. Other 10 rats in group B with 10 rats were designated as a control group and were not given BBN. Whole urinary bladders of all rats were excised at 12 weeks from the beginning of the experiment. Conventional proteomics was performed with high resolution 2‐dimension gel electrophoresis followed by computational image analysis and protein identification using mass spectrometry.

Results:  A comparison of urinary bladder hyperplasia tissue with control tissue showed that five proteins; actin γ2 propeptide, cytokeratin‐20 (CK‐20), proapolipoprotein, α2 actin (α‐cardiac actin) and heat shock 27 kDa protein‐1 were over‐expressed in hyperplastic tissues. Three proteins; transcription factor myocardin, seminal vesicle secretory protein VI (SVS‐VI) precursor and hypothetical protein RMT‐7 were under‐expressed in hyperplastic tissues.

Conclusion:  In our animal mode, BBN‐induced urinary bladder mucosal hyperplasia resulted in an increase in the expression of five proteins and a decrease in the expression of three proteins. Of these, CK‐20 and SVS‐VI seem to be of particular interest. However other method such as Western blotting seems to be needed for confirmation of these proteins and more information on human bladder tissue is needed for clinical application.
Importance of C16 ceramide accumulation during apoptosis in prostate cancer cells
Authors: ETO MASATOSHI , BENNOUNA JAAFAR , HUNTER ORIANA C. , LOTZE MICHAEL T. , AMOSCATO ANDREW A.
Published: March 2006

Aim:  Adenocarcinoma of the prostate is one of the most frequently diagnosed non‐cutaneous cancers and the second leading cause of cancer‐related deaths among men in the United States. To fully understand the role of ceramide during apoptosis induced by androgen ablation, we modified the levels of intracellular ceramide by pharmacological agents as well as through serum deprivation in androgen‐dependent and independent cell lines.

Methods:  Ceramide levels were modified using N‐oleoylethanolamine (NOE), sphingosine‐1‐phosphate (S1P) as well as through serum deprivation, in LNCaP, DU145 and PC‐3 prostate cancer cells. Various methods including nonyl acridine orange staining, propidium iodide staining/cell cycle analysis and lipid analysis were utilized.

Results:  Our results demonstrate that the inhibition of acid ceramidase by NOE enhances the intracellular ceramide levels induced by androgen ablation in androgen‐dependent LNCaP cells, and is accompanied by an increase in apoptotic cells. Sphingosine 1‐phosphate had no effect in rescuing LNCaP cells from apoptosis induced by androgen ablation. Our results also show that serum deprivation causes intracellular ceramide accumulation and apoptosis in androgen‐independent prostate cancer cells.

Conclusions:  Our studies indicate that the increase in intracellular ceramide itself, but not the balance between ceramide and S1P, determines whether LNCaP cells undergo apoptosis. Our results also show that the increase in intracellular ceramide strongly correlates with apoptosis induced by serum deprivation even in androgen‐independent prostate cancer cell lines.
Laparoscopic removal of a retroperitoneal extralobar pulmonary sequestration in an adult
Authors: FURUNO TSUYOSHI , MORITA KEN , KAKIZAKI HIDEHIRO , HARABAYASHI TORU , WATARAI YOSHIHIKO , NONOMURA KATSUYA
Published: March 2006

Abstract  A 41‐year‐old male patient presented with dull left flank pain. A computed tomography (CT) showed a subdiaphragmatic retroperitoneal extra‐adrenal mass. A magnetic resonance image demonstrated it was hypointense on T1 weighted and hyperintense on T2. Serum analyses for adrenal hormones revealed no abnormality. [I131]metaiodo‐benzylguanidene scintigraphy showed no abnormal uptake. The patient underwent laparoscopic removal to manage the symptoms and to make a pathological diagnosis, which was an extralobar pulmonary sequestration. Another congenital lung malformation was not detected on chest CT scan. The symptom was relieved postoperatively.
Thrombolytic therapy for traumatic unilateral renal artery thrombosis
Authors: NAKAYAMA TSUYOSHI , OKANEYA TOSHIKAZU , KINEBUCHI YOSHIAKI , MURATA YASUSHI , IIZUKA KEIJI
Published: March 2006

Abstract  We report a case of traumatic unilateral renal artery thrombosis that was successfully treated by thrombolytic therapy. The patient was a 17‐year‐old woman, who had put her left upper abdomen between a wall and the handle of a ground roller when using it. A computed tomography scan with intravenous contrast showed a lack of contrast in the left kidney. Angiography showed complete occlusion of the left renal artery, and the diagnosis was traumatic left renal artery thrombosis. Following angiography, thrombolytic therapy was performed. Urokinase was administered into the left renal artery, and 360 000 units per 1.5 h was required. Thrombus disappeared and flow of left renal artery was observed. Recovery of left renal function was seen on renoscintigraphy. Surgical maneuvers for traumatic renal artery thrombosis are autotransplantation or thrombectomy generally, but we think that thrombolytic therapy following angiography is a less invasive method and saves warm ischemic time.
Facilitating the technique of laparoscopic running urethrovesical anastomosis using Lapra‐ty absorbable suture clips
Authors: SHICHIRI YASUMASA , KANNO TORU , OIDA TOMOYUKI , KANAMARU HIROSHI
Published: March 2006

Abstract  We herein describe a simplified technique for performing laparoscopic running urethrovesical anastomosis using Lapra‐ty absorbable suture clips (Ethicon, Somerville, NJ, USA) during a laparoscopic radical prostatectomy (LRP). Using two 20 cm absorbable sutures tied together and locked with Lapra‐ty at their tail ends, the initiating mattress sutures are placed in the 5:30–6:30‐o’clock area between the urethra and the bladder neck. The left and right running sutures are then made clockwise from the 6:30–12‐o’clock position and counterclockwise from the 5:30–12‐o’clock position, respectively. Both sutures are locked with proper tension by Lapra‐ty at the 3, 9 and 12‐o’clock positions, and then they are intracorporeally tied together just at the 12‐o’clock position. In the initial 20 cases, this anastomosis took 22.5 min on average to perform. We experienced no major urine extravasation and no anastomotic stricture to date.
First Order Approximation of an Elliptic 3D Singular Perturbation Problem
Authors: López José L. , Sinusía Ester Pérez , Temme Nico M.
Published: March 2006

A three‐dimensional elliptic singular perturbation problem with discontinuous boundary values is considered. The solution of the problem is written in terms of a double integral. A saddle point analysis is used to obtain a first approximation, which is expressed in terms of a function that can be viewed as a generalization of the complementary error function.
Revisiting General and Specific Union Beliefs: The Union‐Voting Intentions of Professionals
Authors: PARK HEEJOON , MCHUGH PATRICK P. , BODAH MATTHEW M.
Published: March 2006

We examine how general and specific beliefs about unions influence the union‐voting intentions of professional employees. Previous research, mainly on nonprofessionals, has found that both beliefs are significant in predicting voting behavior, but that specific beliefs have the stronger effect. Using a structural equation model, we found a causal relationship between general and specific beliefs, and that the total effect of general beliefs is nearly three times as strong as that of specific beliefs.
Definition of sustainable and unsustainable issues in nutrient management of modern agriculture
Authors: Bergström L. , Bowman B.T. , Sims J.T.
Published: March 2006

Abstract. Sustainable management of nutrients in agricultural systems is critical for sufficient production of nutritious foods and to minimize environmental pollution. In this overview, we discuss some of the most important factors influencing nutrient cycling, and how practices for sustainable nutrient management can be optimized. In most cases, problems are associated with excessive use of nutrients (manures, other organic amendments, and inorganic fertilizers). Options for dealing with such problems at the farm level include: reducing nutrient inputs to balance exports, increasing the land area on which manures are applied, and export of excess nutrients from the farm in the form of value‐added products. These strategies can be used singly, or in combination. Nutrients in the human food chain are often not recycled back to primary crop production. To manage such issues, and avoid regional nutrient accumulations, we need to develop a better understanding of large‐scale nutrient flows, and develop policies to manage them. We stress the importance of scale when considering nutrient management in the future.
Critical aspects of potassium management in agricultural systems
Authors: Öborn I. , Andrist‐Rangel Y. , Askekaard M. , Grant C.A. , Watson C.A. , Edwards A.C.
Published: March 2006

Abstract. Fertilizer and manure application rate and timing are often based on the optimal nitrogen rate and not on potassium (K) requirements. This can lead to excess or shortage of K depending on the crop and rotation. In grass‐dominated agricultural production, including many organic farming systems, K has become a critical element, especially in areas dominated by coarse‐textured or organic soils. In this paper we review K management in relation to long‐term sustainability of both the soil resource and the production of crops of high yield and quality. One question for the future is whether we can adopt management options that favour efficient use of K and secure a sustainable future for global K reserves. For example, is it possible to enhance the release rate of K from soil mineral sources so that we require less fertilizer K from K‐bearing salt deposits? A reduction in external K inputs requires improved on‐farm recycling of K in order to reduce losses. We also need a better understanding of soil processes and soil‐plant interactions and decision‐support tools to predict the potential K release from mineral weathering. Certain areas dominated by young, clay‐rich soils can potentially supply enough K, whereas other areas with coarse sandy or organic soils have a very low weathering potential and would thus need external inputs of K.
Nutrient management in low input grazing–based systems of meat production
Authors: Dahlin A.S. , Emanuelsson U. , McAdam J.H.
Published: March 2006

Abstract. Low input grazing‐based meat production is often practised on land where alternative land use is restricted and where high biodiversity warrants specific environmental payments. Although these systems are characterized by low external nutrient inputs, significant nutrient losses may occur per unit of produce, even though losses per unit area are low. If the aim is to have animal production without further eutrophication of watercourses, these losses should be minimized,. However, if nutrient‐poor grasslands characterized by high biodiversity are the aim, some losses must be accepted to balance nutrient inputs by atmospheric deposition. The impact of grazing animals on nutrient dynamics in grasslands is reviewed in this paper, and options to further improve nutrient management are discussed. It is concluded that nutrient management should largely be addressed indirectly through management of animal behaviour in relation to grazing and supplemental feeding, as well as through optimization of the seasonal distribution of livestock size. A case study indicated that N losses from a cattle farm could be reduced considerably by these means, while animal production could actually be improved. Sustainability issues and trends in legislative and social pressures on low input grazing‐based systems of animal production are discussed in relation to nutrient management and practical recommendations.
Perspectives on nutrient management in mixed farming systems
Authors: Watson C.A. , Öborn I. , Eriksen J. , Edwards A.C.
Published: March 2006

Abstract. Changes in agricultural subsidies in Europe and the ready availability of fertilizers have allowed a spatial decoupling of livestock and crop production. This has increased the flow of nutrients that occurs between farms compared to within individual farms. In terms of nutrient cycling, mixed farms provide the opportunity to re‐integrate aspects of agricultural production. The degree of integration between crop and livestock production is denned by the reliance on the use of home‐produced feed compared to imported feed, and is independent of intensity. Management of inputs and/or internal flows offers the scope to improve nutrient use efficiency (NUE) on mixed farms. Greatest uncertainties in calculating NUE are associated with variation in yield and composition of home‐produced feed, and consequent manure composition. Three key areas are addressed to highlight the interchange of nutrients (and risks for losses) between crop and livestock production; (i) the role of livestock diet in manipulating the amount and availability of manure nutrients; (ii) the impact of manure management on nutrient losses; and (iii) nutrient management through the integration of crops and livestock in rotations. While not all the associated issues are unique to mixed farming, these three areas all influence NUE.
Scaling issues in sustainable management of nutrient losses
Authors: Shirmohammadi A. , Djodjic F. , Bergström L.
Published: March 2006

Abstract. To establish strategies for sustainable nutrient management, the priority of each identified element for different user groups and the issue of data transferability from one scale to the next need to be addressed. This is important to avoid developing policies and strategies using inaccurate data. This paper provides a thorough background on such issues and provides data from specific case studies to reflect the impact of scale on the usability and transferability of data. These data show that using information obtained in a laboratory setting for larger scales can generate major errors. Data are also provided regarding the spatial variability in total N and total P measured at different sub‐watersheds within a large watershed. Results from this case study indicate that there is a definite spatial variability in N and P loadings, which makes it difficult to transfer and extrapolate from data measured at one sub‐watershed to the entire watershed. Therefore, it can be concluded that using either measured or simulated data obtained at a small scale to respond to questions for larger scales may be erroneous. Such difficulty may be due to the inherent spatial variability in soils, nutrients, biology and other features of the landscape.
Using Population Count Data to Assess the Effects of Changing River Flow on an Endangered Riparian Plant
Authors: THOMSON DIANE M. , SCHWARTZ MARK W.
Published: March 2006

Abstract:  Methods for using simple population count data to project extinction risk have been the focus of much recent theoretical work, but few researchers have used these approaches to address management questions. We analyzed 15 years of census data on the federally endangered endemic riparian plant Pityopsis ruthii (Small) with the diffusion approximation (DA). Our goals were to evaluate relative extinction risk among populations in two different watersheds (in Tennessee, U.S.A.) and potential effects of variation in managed river flow on population dynamics. Populations in both watersheds had high projected risks of extinction within 50 years, but the causes of this risk differed. Populations of P. ruthii on the Hiwassee River had higher initial population sizes but significantly lower average growth rates than those on the Ocoee River. The only populations with low predicted short‐term extinction risk were on the Ocoee. Growth rates for populations on both rivers were significantly reduced during periods of lower river flow. We found only marginal evidence of a quadratic relationship between population performance and flow. These patterns are consistent with the idea that low flows affect P. ruthii due to growth of competing vegetation, but the degree to which very high flows may reduce population growth is still unclear. Simulations indicated that populations were most sensitive to growth rates in low‐flow years, but small changes in the frequency of these periods did not strongly increase risk for most populations. Consistent with results of other studies, DA estimates of extinction risk had wide confidence limits. Still, our results yielded several valuable insights, including the need for greater monitoring of populations on the Hiwassee and the importance of low‐flow years to population growth. Our work illustrates the potential value of simple methods for analyzing count data despite the challenges posed by uncertainty in estimates of extinction risk.
Levetiracetam: Antiepileptic Properties and Protective Effects on Mitochondrial Dysfunction in Experimental Status Epilepticus
Authors: Gibbs Julie E. , Walker Matthew C. , Cock Hannah R.
Published: March 2006

Summary: Purpose:To assess the anticonvulsant activity of the novel antiepileptic drug, levetiracetam (LEV) in a model of self‐sustaining limbic status epilepticus, and to measure the consequence of LEV treatment on the pattern of mitochondrial dysfunction known to occur after status epilepticus (SE).

Methods:The rat perforant pathway was stimulated for 2 h to induce self‐sustaining status epilepticus (SSSE). Stimulated rats were assigned to one of three treatment groups, receiving intraperitoneal injections of saline, 200 mg/kg LEV, or 1,000 mg/kg LEV, 15 min into SSSE and at 3 times over the next 44‐h period. All animals received diazepam after 3‐h SSSE to terminate seizures. Forty‐four hours later, the hippocampi were extracted and prepared for electrochemical high‐performance liquid chromatography (HPLC), to measure reduced glutathione levels, and for spectrophotometric assays to measure activities of mitochondrial enzymes (aconitase, α‐ketoglutarate dehydrogenase, citrate synthase, complex I, and complex II/III). These parameters were compared between treatment groups and with sham‐operated rats.

Results:LEV administration did not terminate seizures or have any significant effect on spike frequency, although rats that received 1,000 mg/kg LEV did exhibit improved behavioral seizure parameters. Significant biochemical changes occurred in saline‐treated stimulated rats compared with shams: with reductions in glutathione, α‐ketoglutarate dehydrogenase, aconitase, citrate synthase, and complex I activities. Complex II/III activities were unchanged throughout. Rats that received 1,000 mg/kg LEV had significantly improved biochemical parameters, in many instances, comparable to sham control levels.

Conclusions:Despite continuing seizures, administration of LEV (1,000 mg/kg) protects against mitochondrial dysfunction, indicating that in addition to its antiepileptic actions, LEV may have neuroprotective effects.
Status Epilepticus in 12‐day‐old Rats Leads to Temporal Lobe Neurodegeneration and Volume Reduction: A Histologic and MRI Study
Authors: Nairismägi Jaak , Pitkänen Asla , Kettunen Mikko I. , Kauppinen Risto A. , Kubova Hana
Published: March 2006

Summary:  Purpose: Whether status epilepticus (SE) in early infancy, rather than the underlying illness, leads to temporal lobe neurodegeneration and volume reduction remains controversial.

Methods: SE was induced with LiCl‐pilocarpine in P12 rats. To assess acute neuronal damage, brains (five controls, five with SE) were investigated at 8 h after SE by using silver and Fluoro‐Jade B staining. Some brains from the early phase were processed for electron microscopy. To assess chronic changes, brains from nine controls and 13 rats with SE at P12 were analyzed after 3 months by using histology and magnetic resonance imaging (MRI).

Results: MRI analysis of the temporal lobe of adult animals with SE at P12 indicated that 23% of the rats had hippocampal, 15% had amygdaloid, and 31% had perirhinal volume reduction. Histologic analysis of sections from the MR‐imaged brains correlated with the MRI data. Analysis of neurodegeneration 8 h after SE by using both silver and Fluoro‐Jade B staining revealed degenerating neurons located in the same temporal lobe regions as the volume reduction in chronic samples. Electron microscopic analysis revealed irreversible ultrastructural alterations. As with the chronic histologic and MRI findings, interanimal variability was seen in the distribution and severity of acute damage.

Conclusions: Our data indicate that SE at P12 can cause acute neurodegeneration in the hippocampus as well as in the adjacent temporal lobe. It is likely that acute neuronal death contributes to volume reduction in temporal lobe regions that is detected with MRI in a subpopulation of animals in adulthood.
The Effect of Antiepileptic Drugs on 5‐HT1A–Receptor Binding Measured by Positron Emission Tomography
Authors: Theodore William H. , Giovacchini Giampiero , Bonwetsch Robert , Bagic Anto , Reeves‐Tyer Patricia , Herscovitch Peter , Carson Richard E.
Published: March 2006

Summary:  Purpose: To study the effect of antiepileptic drugs (AEDs) on 5‐HT1A–receptor binding in patients with temporal lobe epilepsy. 5‐HT1A–receptor binding, measured by positron emission tomography, is reduced in patients with temporal lobe epilepsy. Antiepileptic drugs may act on the serotonergic system, as shown in animal models, and thus affect receptor‐binding measurements.

Methods: We analyzed the effect of AEDs on 5‐HT1A–receptor binding in 31 patients and 10 normal controls. Patients with structural lesions, progressive neurologic disorders, or taking other medications were excluded. None had a seizure for ≥2 days before positron emission tomography (PET). [18F]FCWAY PET was performed on a GE Advance scanner with continuous EEG monitoring. Functional images of the distribution volume (V) were generated. Anatomic regions of interest were applied to coregistered PET images, after correction for partial‐volume effect.

Results: Patients had significantly higher [18F]FCWAY free fraction (f1) than did controls. No AED effects were observed on interictal [18F]FCWAY binding after correction for plasma free fraction. [18F]FCWAY V/f1 reduction in epileptic foci was not affected by AEDs.

Conclusions: 5‐HT1A‐receptor binding is reduced in temporal lobe epileptic foci after partial‐volume correction. AED plasma free fractions should be measured when PET receptor studies are performed in patients with epilepsy.
Changes in the Disposition of Oxcarbazepine and Its Metabolites during Pregnancy and the Puerperium
Authors: Mazzucchelli Iolanda , Onat Filiz Yilmaz , Ozkara Cigdem , Atakli Dilek , Specchio Luigi M. , Neve Angela La , Gatti Giuliana , Perucca Emilio
Published: March 2006

Summary:  Purpose: To determine potential changes in the plasma concentrations of oxcarbazepine (OXC) and its metabolites during pregnancy and puerperium.

Methods: Five women receiving OXC monotherapy were followed prospectively during pregnancy and the puerperium. Four women were enrolled in the first trimester, and one woman, 2 weeks before delivery. Steady‐state concentrations of OXC, its active R‐(‐)‐ and S‐(+)‐monohydroxy derivatives (MHD), and the additional metabolite carbamazepine‐10,11‐trans‐dihydrodiol (DHD) were measured at regular intervals by an enantioselective HPLC assay.

Results. In all samples, S‐(+)‐MHD was the most abundant compound in plasma and accounted almost entirely for the amount of active moiety (defined as the molar sum of OXC, R‐(‐)‐MHD, and S‐(+)‐MHD) found in the circulation. The dose‐normalized concentrations of active moiety decreased markedly during gestation and, in four of the five patients, increased strikingly after delivery. Plasma concentrations of S‐(+)‐MHD mirrored closely the levels of the active moiety. Plasma concentrations of the parent drug and other metabolites also tended to decrease during pregnancy and to increase after delivery.

Conclusions: During treatment with OXC, S‐(+)‐MHD is by far the most abundant active compound in plasma. The concentration of this metabolite as well as the active moiety may decrease markedly during pregnancy and may increase severalfold after delivery. Because of these striking pharmacokinetic changes, the clinical response should be monitored closely in OXC‐treated women throughout pregnancy and the puerperium.
Vitamin D Levels and Bone Turnover in Epilepsy Patients Taking Carbamazepine or Oxcarbazepine
Authors: Mintzer Scott , Boppana Prashanthi , Toguri Jeanne , DeSantis Anthony
Published: March 2006

Summary:  Purpose: Evidence suggests that enzyme‐inducing antiepileptic drugs (AEDs) may decrease serum 25‐hydroxyvitamin D (25‐OHD) levels and increase bone turnover. We sought to determine whether these are affected by treatment with carbamazepine (CBZ) or oxcarbazepine (OXC).

Methods: We measured serum levels of 25‐OHD, parathyroid hormone (PTH), osteocalcin (OCLN), bone alkaline phosphatase (BAP), and urinary N‐telopeptides of type I collagen cross‐links (NTX) in normal controls (n = 24) and in epilepsy patients taking CBZ (n = 21) or OXC (n = 24) in monotherapy. CBZ patients were subsequently switched overnight to OXC monotherapy, and after 6 weeks, the tests were repeated.

Results: 25‐OHD levels were lower in each drug‐treated group (OXC, 19.4 ± 2.3 pg/ml; CBZ, 20.4 ± 2.4) than in the controls (27.5 ± 2.8) (ANOVA, p = 0.052). This difference was significant for the OXC group (p < 0.05). PTH, BAP, and NTX did not differ significantly among groups. OCLN levels were somewhat elevated in the OXC group (2.79 ± 0.47 ng/ml) and more clearly and significantly elevated in the CBZ group (3.63 ± 0.36) compared with controls (2.38 ± 0.41) (p = 0.053). Because the data were very similar between OXC and CBZ groups, they were combined to increase statistical power. The combined drug‐treatment group had significantly higher BAP (p = 0.02) and lower 25‐OHD (p = 0.015) than did controls. The latter remained significant even after accounting for the confounding effects of age on 25‐OHD levels (p < 0.05). No significant differences were found after CBZ patients were switched to OXC.

Conclusions: Epilepsy patients taking OXC or CBZ have significantly lower 25‐OHD than do normal controls, with a pattern of changes in other bone biomarkers suggestive of secondary hyperparathyroidism. It may be prudent for patients taking CBZ or OXC to be prescribed 25‐OHD replacement.
Onset of Action of Levetiracetam: A RCT Trial Using Therapeutic Intensive Seizure Analysis (TISA)
Authors: Stefan Hermann , Wang‐Tilz Ying , Pauli Elisabethe , Dennhöfer Stephanie , Genow Alexandra , Kerling Frank , Lorber Bogdan , Fraunberger Britta , Halboni Petra , Koebnick Corinna , Gefeller Olaf , Tilz Christian
Published: March 2006

Summary:  Objectives: To correlate the onset of clinical effects of add‐on levetiracetam (LEV) therapy with daily serum LEV concentration, in pharmacoresistant focal epilepsies, using the TISA method.

Methods: 25 adult patients (aged >16 years) with pharmacoresistant focal epilepsies undergoing presurgical evaluation at the Epilepsy Center Erlangen were enrolled in the study. Eligible patients on a maximum of one other antiepileptic drug (AED) were recruited into the 48‐hour baseline phase. Those who had at least two seizures during this phase were randomized into the seven‐day treatment phase, when they received either LEV or placebo, under continuous day‐and‐night video‐EEG monitoring. The starting daily dose of LEV was 500 mg bid, titrated from the second treatment day to 1000 mg bid. The peak serum concentration of LEV was monitored daily at 8:00 am (one hour after drug administration) for every patient. The number and duration of seizures per 24h (N/24h and D/24h respectively) were investigated.

Results: 23 patients completed the study (LEV group n = 11 and placebo group n = 12). Seven patients in the LEV group and two patients in the placebo group achieved seizure‐freedom during the treatment phase. The intergroup comparison of the decrease in N/24h and D/24h from the baseline phase to the treatment phase was in favor of the LEV group (p < 0.05). A significant effect of LEV on D/24h was seen as early as the second treatment day (p = 0.013), becoming more apparent on the third treatment day (p = 0.009).

Conclusion: The present study objectively quantified the correlation between the anticonvulsant effects of LEV in focal epilepsies and the peak serum concentration of the drug. For the first time, direct measurement was used to demonstrate the onset of action of LEV to be two days after drug initiation.
EEG Features in Idiopathic Generalized Epilepsy: Clues to Diagnosis
Authors: Betting Luiz Eduardo , Mory Susana Barreto , Lopes‐Cendes Iscia , Li Li M. , Guerreiro Marilisa M. , Guerreiro Carlos A. M. , Cendes Fernando
Published: March 2006

Summary:  Purpose: To investigate the EEG profile and its contribution for diagnosis and management in a group of patients with a clinical diagnosis of idiopathic generalized epilepsy (IGE) who were referred to a tertiary hospital.

Methods: We retrospectively studied clinical and EEG features of 180 consecutive patients with IGE. Eighty patients were diagnosed with juvenile myoclonic epilepsy (JME), 35 had absence epilepsy (AE), 13 had generalized tonic–clonic seizures on awakening (GTCS‐A), 28 had generalized tonic–clonic seizures only (TCS), and 24 had adult‐onset idiopathic generalized epilepsy (AIGE). The EEGs were classified in typical (synchronous generalized spike or polyspikes‐and‐wave discharges with normal background), atypical (with clear focalities or asymmetries), and normal.

Results: The 493 EEG exams were analyzed. The first EEG was normal in 45% of the 180 patients, and only 33% had typical abnormalities. AE had a higher proportion of typical examinations and needed fewer sequential examinations to register a typical abnormality compared with the other groups. By contrast, the serial EEG profile of TCS and AIGE showed a higher proportion of normal and atypical EEG findings.

Conclusions: These findings support previous recommendations that IGE patients should be treated with appropriate therapy based on clinical history. Waiting for a typical abnormal EEG pattern can generate an unacceptable delay in the correct diagnosis and treatment of these patients. In patients with long‐term epilepsy, the diagnosis may be difficult. Furthermore, serial EEGs can help to elucidate the syndromic diagnosis, especially in patients with TCS and AIGE.
Early Pattern of Epilepsy in the Ring Chromosome 20 Syndrome
Authors: Ville Dorothée , Kaminska Anna , Bahi‐Buisson Nadia , Biraben Arnaud , Plouin Perrine , Telvi Louise , Dulac Olivier , Chiron Catherine
Published: March 2006

Summary:  Purpose: The characteristics of epilepsy in ring chromosome 20 have been reported in adolescents and adults. The mode of onset most often remains imprecise. To clarify this onset period, we studied the early‐onset features in our personal series and in the reported pediatric cases.

Methods: Our series comprises one child with an onset of epilepsy in the neonatal period and five others with an onset before age 8 years. The cases in the literature with an epilepsy onset before 8 years also were reviewed.

Results: Seizures in the neonatal period were described as motor seizures. Our personal patient with a neonatal onset had severe psychomotor delay. In both infancy and early childhood, the EEG showed no interictal frontal localization of the anomalies, and no long‐lasting seizure was recorded. Seizures with terror and hallucinations usually appeared from about age 4 years. It is not before the age of 8 years that the usual interictal EEG pattern appeared of rhythmic theta slow‐waves activity with spikes predominating in frontal areas described in adolescence and adulthood. The interictal EEG showed 1‐ to 2‐Hz delta slow waves and spike‐and‐waves predominating in frontal areas, but no physiologic activity.

Conclusions: In ring 20 chromosome, specific epilepsy features are lacking in the neonate, but the whole phenotype shows a more severe expression in terms of mental delay. The characteristic frontal EEG pattern and ictal terror do not appear before age 4 to 5 years.
Cardiac Autonomic Control in Patients with Refractory Epilepsy before and during Vagus Nerve Stimulation Treatment: A One‐Year Follow‐up Study
Authors: Ronkainen Eija , Korpelainen Juha T. , Heikkinen Esa , Myllylä Vilho V. , Huikuri Heikki V. , Isojärvi Jouko I. T.
Published: March 2006

Summary:  Purpose: To elucidate possible effect of vagus nerve stimulation (VNS) therapy on interictal heart rate (HR) variability in patients with refractory epilepsy before and after 1‐year VNS treatment.

Methods: A 24‐hour electrocardiogram (ECG) was recorded at the baseline and after 12 months of VNS treatment in 14 patients with refractory epilepsy, and once in 28 healthy age‐ and sex‐matched control subjects. Time and frequency domain measures, along with fractal and complexity measures of HR variability, were analyzed from the ECG recordings.

Results: The mean value of the RR interval (p = 0.008), standard deviation of N‐N intervals (SDNN) (p < 0.001), very‐low frequency (VLF) (p < 0.001), low‐frequency (LF) (p = 0.001), and high‐frequency (HF) (p = 0.002) spectral components of HR variability, and the Poincaré components SD1 (p = 0.005) and SD2 (p < 0.001) of the patients with refractory epilepsy were significantly lower than those of the control subjects before VNS implantation. The nocturnal increase in HR variability usually seen in the normal population was absent in patients with refractory epilepsy. VNS had no significant effects on any of the HR‐variability indexes despite a significant reduction in the frequency of seizures.

Conclusions: HR variability was reduced, and the nocturnal increase in HR variability was not present in patients with refractory epilepsy. One‐year treatment with VNS did not have a marked effect on HR variability, suggesting that impaired cardiovascular autonomic regulation is associated with the epileptic process itself rather than with recurrent seizures.
Late Seizures in Patients Initially Seizure Free after Epilepsy Surgery
Authors: Schwartz Theodore H. , Jeha Lara , Tanner Adrianna , Bingaman William , Sperling Michael R.
Published: March 2006

Summary:  Purpose: Surgery for medically intractable epilepsy is currently the most effective means of achieving seizure control. Although relatively few long‐term outcome studies have been performed, evidence is mounting that the possibility of late seizure recurrence exists, even after an early seizure‐free period. No published reports document the rate and predictors of late recurrence in a large series of patients undergoing surgery in the magnetic resonance imaging (MRI) era.

Methods: We retrospectively queried the databases of two epilepsy surgery centers. Patients eligible for study had preoperative MRI scans, were seizure free for 1 year after surgery, and had a minimal follow‐up period of 3 years. Patients with tumors or vascular lesions were excluded. We performed log‐rank comparison of Kaplan–Meier product limit estimates for categoric variables and used a Cox proportional hazards model for continuous variables. Variables that were significant (p < 0.05) on a univariate screen were entered into a multivariate forward step‐wise Cox regression.

Results: The study included 285 patients, 254 with medial temporal lobe (MTLE) and 31 with neocortical epilepsy. The probability of having a single seizure after being seizure free for 1 year was 18.3% at 5 years and 32.7% at 10 years. However, only 13% were not seizure free at the last follow‐up. Predictors of late recurrences on both uni‐ and multivariate analysis were the presence of preoperative generalized tonic–clonic (GTC) seizures in patients with neocortical epilepsy and late age at surgery in patients with MTLE. MRI results and location of surgery were not predictive.

Conclusions: Although the risk of at least one recurrent seizure after initially successful epilepsy surgery is relatively high, the rate of recurrent intractability is low. The finding that late age at surgery and presence of preoperative GTC seizures are predictors of late recurrence indicates the importance of patient selection and early surgery for persistent seizure control.
Discontinuation of Anticonvulsant Medication after Epilepsy Surgery in Children
Authors: Hoppe Christian , Poepel Annkathrin , Sassen Robert , Elger Christian E.
Published: March 2006

Summary:  Purpose: To evaluate the long‐term outcome of medication‐reduction/discontinuation trials after epilepsy surgery in pediatric patients.

Methods: Of the total Bonn pediatric surgical sample (1988–2001; n = 251), we were able to obtain postsurgical follow‐up data for 232 patients. We surveyed 140 of these patients by using a standardized telephone interview that addressed medication‐reduction/discontinuation trials.

Results: Of the 140 surveyed patients, 102 completely discontinued medication. Seven of these patients had recurring seizures that were controlled again after restarting the medication. Of 102 patients, 101 were completely seizure free during the 3 months before the survey. Postsurgical epileptic events before the trial significantly increased the risk for recurring epileptic events after the trial. Two surveyed patients lost postsurgical seizure freedom after medication reduction. We were also able to identify from the records another nine patients with complete medication discontinuation and seven patients with medication reduction. Two of these latter patients lost postsurgical seizure freedom despite restarting their medication. The total rate of patients with medication‐reduction/discontinuation trials was 55%. The seizure recurrence rate in these patients was 10%. Recurring seizures could not be controlled by restarted medication in 3% of the trials. Currently, 90% of patients with discontinuation trials were seizure free without medication.

Conclusions: The reduction/withdrawal of anticonvulsant medication after successful epilepsy surgery has a low risk of seizure recurrence for pediatric patients in long‐term follow‐up, particularly in cases of complete postsurgical seizure freedom before the trial.
Effects of Temporal Lobe Epilepsy on Retrograde Memory
Authors: Lah Suncica , Lee Teresa , Grayson Sandra , Miller Laurie
Published: March 2006

Summary: Purpose:In a previous investigation (Lah et al., 2004), we found deficits in retrograde memory in patients who had undergone temporal lobectomy (TL). In this study, we set out to determine whether such deficits are present before surgery in patients with temporal lobe epilepsy (TLE).

Methods:Memory for public and autobiographic facts and events was assessed in patients with focal left‐sided (n = 15) or right‐sided (n = 14) TLE and healthy control subjects (n = 15). The impact of epilepsy and underlying cognitive deficits on retrograde memory also was examined.

Results:Patients with left TLE demonstrated retrograde memory deficits across domains. Patients with right TLE showed defective recall only in the autobiographic domain. Young age at onset (younger than 14 years) was associated with greater difficulties in recall of famous events, and patients receiving polytherapy had significantly reduced recall of autobiographic events compared with those receiving monotherapy. In most cases, deficient memory for the past was associated with impairments in other cognitive skills, especially language abilities.

Conclusions: In unoperated‐on patients with TLE, we found deficits in retrograde memory that were similar to those seen after TL, with the pattern of deficits being influenced by side of lesion, anticonvulsant medication, and word‐finding deficits. Unlike patients tested after right TL, patients with right TLE did not have difficulty recalling details of famous events, which raises the possibility that right TL results in a decline in this aspect of retrograde memory.