Sustained efficacy and long-term safety of oxcarbazepine: one-year open-label extension of a study in refractory partial epilepsy

PURPOSE: To evaluate the long-term efficacy, tolerability, and safety of oxcarbazepine (OXC) in medically refractory partial epilepsy. METHODS: This study is the open-label extension phase that followed a multicenter, randomized, double-blind, dose-response clinical study of OXC monotherapy in patients with medically refractory partial epilepsy. We analyzed the efficacy, tolerability, and safety of OXC during the first 48 weeks of open-label therapy. To evaluate efficacy, we compared the change in seizure frequency throughout the 48 weeks of treatment with OXC with the baseline seizure frequency that preceded the double-blind phase of the core study by an intent-to-treat and completer analysis. Safety and tolerability were evaluated by using an intent-to-treat analysis. RESULTS: Of the 87 patients enrolled in the double-blind study, 76 patients participated in the open-label extension phase. Fifty-five (72%) patients completed 48 weeks of open-label treatment on a median OXC dose of 2,400 mg/day. Based on an intent-to-treat analysis, the median reduction in seizure frequency was 47%(p = 0.0054); the 50 and 75% responder rates were 46.1 and 25.0%, respectively, with 6.6% of patients remaining seizure free. The completer analysis yielded comparable efficacy results. OXC was well tolerated, with 13% of patients exiting because of adverse events. The six most common adverse events, irrespective of their causal relation to OXC, were dizziness, headache, fatigue, diplopia, nausea, and rash. For the most part, these adverse events tended to be transient. CONCLUSIONS: The efficacy of OXC is sustained with good safety and tolerability profiles during long-term treatment of patients with medically refractory partial epilepsy.     

Treatment modalities and outcome of the renal victims of the Marmara earthquake

BACKGROUND/AIMS: Circulating CD14+CD16+ monocytes, a potent phagocytosing and antigen-presenting monocyte population, have been reported to be expanded in patients on hemodialysis (HD). In this study, changes in the population of CD14+CD16+ monocytes were analyzed during a single session of HD therapy, and the influence of dialyzer membrane materials on these monocytes was investigated. METHODS: Nine patients were hemodialyzed using regenerated cellulose (RC) membranes and thereafter polysulfone (PS) membranes. Peripheral blood cells were taken from these subjects, and these cells were stained with anti-CD14 and anti-CD16 antibodies. The percentages of CD14- and CD16-expressing monocytes were analyzed by two-color flow cytometric analysis. Moreover, the serum soluble CD14 (sCD14) levels were measured with an ELISA kit. RESULTS: It was found that CD14+CD16+ monocytes before HD were significantly increased in patients on HD as compared to healthy controls. In the RC group, CD14+CD16+ monocytes were decreased at both 30 and 240 min after the initiation of HD. The reduction rate of CD14+CD16+ monocytes in the RC group was higher than that in the PS group. There was no significant difference in sCD14 levels between the two groups. CONCLUSION: Monocytes are activated in patients on HD. Furthermore, the population of CD14+CD16+ monocytes was stimulated to a greater extent during HD in the RC group than in the PS group. The significant reduction in CD14+CD16+ monocytes by RC membranes indicated that the level of CD14+CD16+ monocytes is a sensitive marker for the biocompatibility of HD membranes.     

Renal replacement therapies in the aftermath of the catastrophic Marmara earthquake

BACKGROUND: Renal replacement therapy is of vital importance in the treatment of crush syndrome victims, who are frequently encountered after catastrophic earthquakes. The Marmara earthquake, which struck Northwestern Turkey in August 1999, was characterized by 477 victims who needed dialysis. METHOD: Within the first week of the disaster, questionnaires containing 63 clinical and laboratory variables were sent to 35 reference hospitals that treated the victims. Information considering the features of dialyses obtained through these questionnaires was submitted to analysis. RESULTS: Overall, 639 casualties with renal complications were registered, 477 of whom (mean age 32.3 +/- 13.7 years, 269 male) needed dialysis. Among these, 452 were treated by a single dialysis modality (437 intermittent hemodialysis, 11 continuous renal replacement therapy and 4 peritoneal dialysis), while 25 victims needed more than one type of dialysis. In total, 5137 hemodialysis sessions were performed (mean 11.1 +/- 8.0 sessions per patient) and mean duration of hemodialysis support was 13.4 +/- 9.0 days; this duration was shorter in the non-survivors (7.0 +/- 8.7 vs. 10.0 +/- 9.8 days, P = 0.005). Thirty-four victims who underwent continuous renal replacement therapy had higher mortality rates (41.2 vs. 13.7%, P < 0.0001). Only eight victims were treated by peritoneal dialysis, four of whom also required hemodialysis or continuous renal replacement therapy. The mortality rate in the dialyzed victims was 17.2%, a significantly higher figure compared to the mortality rate of the non-dialyzed patients with renal problems (9.3%; P = 0.015). CONCLUSION: Substantial amounts of dialysis support may be necessary for treating the victims of mass disasters complicated with crush syndrome. Dialyzed patients are characterized by higher rates of morbidity and mortality.     

The graded anxiety test: a novel test of murine unconditioned anxiety based on the principles of the elevated plus-maze and light-dark test

The trajectory of secretory vesicles to their fusion sites at the plasma membrane is expected to give insight into the mechanisms that underlie vesicle transport, maturation and the initiation of membrane fusion. Evanescent-wave (EW) microscopy allows the tracking of fluorescently labeled granules and vesicles prior to fusion with nanometer precision in xy-direction. At the same time, the exponential sensitivity of granular fluorescence to experimental parameters can preclude quantitative estimates of the granule's approach to the plasma membrane. Thus, it has remained controversial to which extent axial distance can be obtained from simple intensity measurements. We used the information contained in a stack of images acquired at 80-125 nm penetration depth of the EW field to estimate individual granule diameter and axial distance. A population analysis on 90 granules revealed an average diameter of 305 +/- 47 nm, below the diffraction-limited 352 +/- 31 nm obtained from xy measurements at fixed depth penetration. Stimulation of exocytosis by potassium depolarization resulted in the selective loss of the 18 +/- 5% of granules located closest to the plasma membrane, while a second population of granules located 60 nm deeper within the cytoplasm increased by recruitment of granules previously located at > or = 120 nm depth. These measurements extend and corroborate previous observations at fixed penetration depth of functionally distinct granule populations. Parameters influencing the accuracy of the parameter estimation are evaluated in the appendix.     

Nephropathy and retinopathy in type 2 diabetic patients living at moderately high altitude and sea level

BACKGROUND: High-altitude-induced hypoxia results in various diseases, such as chronic mountain sickness and high altitude retinal edema, and may affect severity and incidence of some cardiovascular diseases. In order to evaluate the effects of moderately high altitude on diabetic nephropathy and retinopathy, a cross-sectional study was planned. MATERIAL METHOD: Long-term type II diabetic residents of sea level (n=75, 38 male, 37 female, mean age 51.9+/-10.5 in Trabzon and Zonguldak cities) and moderately high altitude (h = 1,727 m, n = 73, 28 male, 45 female, mean age 48.3+/-12.1, Van city) were compared. RESULTS: No difference was observed in terms of age, gender, diabetes duration, body mass index, smoking, systolic, diastolic, and mean arterial blood pressure values, serum glucose levels, cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, hemoglobin, HbA1C, hypertension control, or blood pressure medications and retinopathy incidence. Mean 24 h protein excretion (210.0+/-139.9, 127.8+/-112.1 mg; P=0.00), proteinuria prevalence (57.5% versus 33.3%, p=0.003), and serum creatinine levels (1.04+/-0.22 versus 0.84+/-0.21, p = 0.00) were significantly higher in the highlanders, glomerular filtration rate (GFR) was significantly lower in sea level (SL) patients (90.9+/-26.5 versus 83+/-21.1, p=0.05). CONCLUSION: Tendency to diabetic nephropathy as indicated by higher proteinuria and creatinine levels is increased among type 2 diabetic patients living at moderately high altitude. Prospective studies are needed to confirm these findings.     

Contrast-enhanced CT and MRI findings of atypical hepatic Echinococcus alveolaris infestation

Diagnosis of liver infestation by Echinococcus alveolaris (EA) is based on serological and radiological findings. In this report, we present a 15-year-old girl with atypical hepatic EA infestation showing central punctate calcifications and contrast enhancement on the portal and late phases of CT and MRI. CT showed a hypodense mass involving more than half of the liver with prominent central calcifications. MRI revealed hypointense signal of the infiltrative mass on both T1- and T2-weighted images. Contrast enhancement is a unique finding in hepatic EA infestation that may cause difficulties with diagnosis. MRI may provide invaluable information in the diagnosis of EA infestation of the liver, either by disclosing the infiltrative pattern of infestation without significant effect to vascular structures, or by the signal characteristics.     

The prevalence of stress urinary incontinence among women operated on for abdominal wall hernias

The high co-occurrence of an abdominal wall hernia (AWH) and stress urinary incontinence (SUI) suggests that there is a common factor in the etiopathogenesis of these disorders in these patients.     

Efficacy of intraperitoneal cisplatin as consolidation therapy in patients with pathologic complete remission following front-line therapy for epithelial ovarian cancer. Consolidative intraperitoneal cisplatin in ovarian cancer

OBJECTIVE: The aim of this study is to evaluate the efficacy of intraperitoneal cisplatin as consolidation treatment in epithelian ovarian cancer patients with complete pathologic response following front-line platin-based chemotherapy. PATIENTS AND METHODS: Thirty patients who had no evidence of disease as assessed by second-look laparotomy following chemotherapy for stage III epithelial ovarian cancer were given three courses of intraperitoneal cisplatin (100 mg/m(2)) with three weekly intervals as consolidation therapy. RESULTS: Median age was 50 years. After a median follow-up period of 37 months, 16 patients are being followed with no evidence of disease. Eleven patients developed recurrent disease. Median disease-free survival was 50 months. Median overall survival is not reached. WHO grades 3-4 toxicity criteria were emesis in 19 patients (63.3%), abdominal pain in 5 (16.7%) and nephrotoxicity in 2 (6.7%) patients. Catheter-related complications were infection/peritonitis in one and catheter malfunction in one patient. There were no serious hematologic side effects that required transfusions or caused treatment delays. None of the patients developed serious neurologic toxicity. Treatment had to be stopped early in four patients who refused further treatment due to abdominal pain, nausea ::and vomiting. Dose reductions were required in five patients.CONCLUSION: Our results suggest that intraperitoneal cisplatin is a feasible regimen that may provide a favorable outcome in terms of progression-free survival in patients with a complete pathologic response following front-line treatment for ovarian cancer. Further randomized trials are required to evaluate the role of consolidation treatment in this setting.     

Intracranial calcification and tumoural calcinosis during vitamin D therapy

Extraskeletal calcifications are frequently observed in patients with chronic renal failure. However, clinically, they usually remain silent. In this report, we describe two patients with massive extraskeletal calcifications that caused significant morbidity. The first patient had tumoural calcification located on the shoulder and the second patient had severe neurological symptoms caused by intracranial calcifications. High calcium phosphorus product and severe secondary hyperparathyroidism were present in both patients. Furthermore, they both received inappropriately high doses of active vitamin D, even though they failed to respond to this therapy. We suggest to monitor closely the calcium, phosphorus and parathyroid hormone levels during calcitriol therapy and to perform parathyroidectomy, without delay, in patients who were resistant to calcitriol.