Association between APOE polymorphisms and mesial temporal lobe epilepsy with hippocampal sclerosis.

To evaluate the hypothetical link between apolipoprotein E (APOE) polymorphisms and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and whether presence of APOE epsilon4 allele shortens the latent period between febrile seizures and epilepsy. A further interest is whether presence of APOE epsilon4 allele has an impact on severity of the disease. Forty-seven patients with MTLE-HS were compared with 62 controls. APOE polymorphisms were determined from lymphocytes by standard methods. Eight patients (17%) and 10 controls (16.1%) were demonstrated to have one APOE epsilon4 allele. There was not any statistically significant difference in APOE epsilon4 frequency between patients and controls (P > 0.05). There was not any difference statistically according to onset age of epilepsy and the presence of APOE epsilon4 allele within patient group. APOE epsilon4 polymorphisms did not influence the severity of epilepsy. APOE epsilon4 polymorphisms had no impact on outcome after surgery. Patients with bilateral memory deficits, bilateral hippocampal atrophy and with bilateral epileptiform interictal EEG transients, were independently compared with patients having unilateral features and there were not any statistically significant differences. This study has found no association between APOE epsilon4 polymorphisms and presentation of MTLE-HS in a group of Turkish patients.

Efficacy of 7-day treatment with metronidazole+miconazole (Neo-Penotran) - a triple-active pessary for the treatment of single and mixed vaginal infections.

OBJECTIVE: To evaluate the efficacy of Neo-Penotran pessaries (metronidazole 500 mg + miconazole nitrate 100 mg) in candidal, bacterial and trichomonal vaginitis and in mixed vaginal infections. METHOD: Ninety-seven patients with clinical diagnosis of vaginitis entered this open, non-comparative study. Each patient inserted one pessary twice daily for 7 days. Gynecological and microbiological assessments were carried out before, and 8-10/21-23 days after the start of treatment. RESULTS: Vaginitis symptoms were resolved in 91% of the 74 patients evaluated, and improved in a further 7%. Microbiological cure rates were 97.3% for trichomonal, 86.6% for bacterial and 81% for candidal vaginitis. Recurrence rates were 2.7, 3.8 and 16.1%, respectively. Overall microbiological cure rate for mixed infections was 86%, with 93% for trichomonal+bacterial, and 73% for bacterial+candidal vaginitis. In two out of three cases with trichomonal+bacterial+candidal infection, the microorganisms were eradicated completely. CONCLUSION: Neo-Penotran provides immediate and effective treatment for vaginitis, irrespective of single or multiple infection, even when the diagnosis may be uncertain.

GABA and L-glutamic acid release in en bloc resection slices of human hippocampus: an in vitro microdialysis study.

The interaction of neurotransmitters has been a major interest in pathophysiological conditions like epilepsy. In vivo microdialysis has recently gained much validity in measuring neurotransmitter release in experimental animals. However, there is a paucity of data concerning its use in humans on the grounds of safety considerations. Microdialysis experiments were performed using the hippocampal head region removed from patients with medically intractable seizures, who underwent surgery for mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Following en bloc resection, the tissues were immediately transferred to the essential in vitro milieu. Slices were incubated in lactated Ringer's solution and microdialysis probes inserted into the slices were perfused with artificial cerebrospinal fluid (aCSF). When the K+ concentration of aCSF was elevated to 100 mM, GABA and L-glutamic acid levels increased by 293% and 177%, respectively. This method may serve as an experimental model for human brain, to throw more light on the interactions between GABA and L-glutamic acid in hippocampal tissues obtained from patients with MTLE-HS.

Ictal spitting during a left emporal lobe-originated complex partial seizure: a case report.

We present a 35-year-old male patient with intractable temporal lobe epilepsy in whom spitting automatism was documented by ictal recordings during seizures. Spitting is an uncommon automatism and occurs mainly with right-sided, nondominant, temporal focus. However, our patient had left mesial temporal sclerosis with nonverbal memory impairment, but intracarotid amobarbital test demonstrated language and memory dominance on the right hemisphere. The authors feel that this case supports the hypothesis of a nondominant, temporal lobe origin for the spitting automatism.

Surgical outcome of epilepsy patients evaluated with a noninvasive protocol.

Surgery is now an accepted treatment for some medically intractable epilepsies. Presurgical evaluation is particularly important for the localization of the epileptogenic zone, which may necessitate sophisticated imaging techniques and intracranial electroencephalogram (EEG) recordings. If patients are carefully selected, however, successful results can be achieved with noninvasive evaluation methods. Seventy-seven patients were operated on for intractable seizures. All patients underwent EEG, neuropsychological, psychiatric, and magnetic resonance imaging investigations. Ictal EEG-video recording was performed in all nonlesional and in some lesional cases that had discordant data. Selective amygdalo-hippocampectomy was performed on patients with mesial temporal lobe epilepsy (MTLE), an extended or a limited lesionectomy was performed on patients with structural lesions, and a lesionectomy with deafferentation was performed on two patients with West syndrome. Electrocorticography was not used. Temporal lobe directed surgery was performed in 63.6% of the cases. The pathological examinations of all cases showed hippocampal sclerosis (HS) in 43%, tumor or tumor-like lesions in 36%, and cortical dysplasia in 5% of patients. After a mean follow-up of 17 months (range, 2-53), 75% of the patients were seizure-free with or without aura and 15% had a marked improvement, whereas 10% did not benefit from surgery. Neuropsychological outcome of patients with MTLE and HS also showed worthwhile results. Our patients, who were evaluated without pre- and perioperative intracranial recordings and other sophisticated techniques, had an outcome comparable to those in other series from more experienced centers. Our experience indicates that successful results, especially for patients with MTLE-HS and lesion-related epilepsies, can be obtained at centers with limited resources if the diagnoses and evaluation procedures are performed carefully.

Total acid soluble and insoluble carnitine levels in human brain tumors.

Carnitine has two main functions, i.e., transporting long-chain fatty acids into the mitochondrial matrix for beta-oxidation to provide cellular energy and modulating the rise in intramitochondrial acyl-CoA/CoA ratio, which relieves the inhibition of many intramitochondrial enzymes involving glucose and amino acid catabolism. The present study examined the acid soluble carnitine (ASCAR) acid insoluble carnitine (AICAR) and total carnitine (TCAR) concentrations of 50 human brain tumor tissues and 11 normal brain tissues. The ASCAR levels significantly higher in gliomas and meningiomas than brain, however similar to brain in metastatic adenocarcinomas. AICAR levels were lower than brain in all tumors with the exception of a medullablastoma. TCAR levels were similar to brain in all tumor types. Decreased AICAR levels may be due to increased utilization of lipids or enhanced phospholipid and cholesterol synthesis which is need for increased membrane synthesis or formation of eicosanoids. Also decreased concentrations may be a reflection of camitine and its acylesters role in preserving the physiologic membrane structure function from oxidative damage.

The effect of epidural cooling on lipid peroxidation after experimental spinal cord injury.

STUDY DESIGN: The effect of epidural space perfusion with chilled saline solution (% 0.9 NaCl) on lipid peroxidation after experimental spinal cord injury in rats was evaluated. OBJECTIVES: The extent of lipid peroxidation is a useful parameter for evaluating the cellular disturbance caused by spinal cord trauma in experimental conditions. The protective effects of hypothermia against neurological injury resulting from trauma or ischemia both in experimental and clinical situations have been demonstrated. SETTING: Departments of Neurosurgery and Biochemistry, Cerrahpasa Medical School, Istanbul, Turkey. METHODS: Twenty-five female Wistar Albino rats were used. There were five rats in group I (sham-operated), seven rats in group II (trauma), and eight rats in group III (epidural cooling). The remaining five rats were used for the pilot study to determine the spinal cord and body temperature. A clip compression method was used to produce acute spinal cord injury. In group III, 30 min after the trauma the injured spinal cord was cooled by perfusion of the epidural space with chilled saline solution (% 0.9 NaCl) with a flow rate of 5 ml/min for 30 min. At 2 h after trauma, all rats other than the ones used in the pilot study, were sacrificed and the spinal cords were excised. The extent of lipid peroxidation in the spinal cord was assessed by measuring the tissue content of malonil dialdehyde (MDA). RESULTS: The tissue MDA contents were 1.58 micromol MDA/gram wet weight (gww) in group I (sham-operated), 2.58 micromol MDA/gww in group 2 (trauma), and 1.77 micromol/gww in group 3 (epidural cooling), the differences being statistically significant. CONCLUSION: The results indicated that epidural cooling of traumatized spinal cord is effective in preventing secondary damage due to the peroxidation of lipid membranes.

Profiles of the fatty acids in the plasma membrane of human brain tumors.

Several studies demonstrated that certain fatty acids have specific effects on tumor cells. n-3 series fatty acids (alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid) may suppress the carcinogenesis, whereas n-6 series fatty acids (arachidonic acid, linoleic acid) may exert tumor promoting effects. In this study, 19 patients with various brain tumors and 12 control brain tissues were studied. n-3, n-6, n-9 unsaturated fatty acids and certain saturated fatty acids levels were measured in the plasma membrane of tumor or control brain tissues by capillary gas chromatography. We found that the level of docosahexaenoic acid from n-3 series fatty acids was significantly lower in gliomas and meningiomas than controls (p = 0.000). Total n-3 fatty acids level was also significantly lower in tumors than controls (p = 0.000). The levels of linoleic acid, arachidonic acid and dihomogamma linolenic acid from n-6 series were significantly higher in gliomas and meningiomas compared with controls (p = 0.000). Total n-6 fatty acids level was also significantly higher in tumors than controls (p = 0.000). Furthermore, in total n-9 fatty acids, total unsaturated fatty acids and total saturated fatty acids levels, there were no significant differences in gliomas and meningiomas compared with controls (p = 0.6840, p = 0.4388 and p = 0.4343, respectively). This findings suggest that n-6 fatty acids can act as a tumor-promoting agent in human brain tumors.

Prostaglandin E2 levels in human brain tumor tissues and arachidonic acid levels in the plasma membrane of human brain tumors.

Arachidonic acid is stored in the cell membrane and released when the cell is activated by appropriate stimuli. It is the substrate for prostaglandins. Both experimental and human tumors often synthesize high levels of prostaglandins, most notably prostaglandin E2 (PGE2). Some experiments suggest that these compounds increase tumor growth through their actions on host immunocytes. In this study, 22 patients with various brain tumors and 12 control brain tissues were studied. PGE2 levels in tissue samples were measured by ELISA. Arachidonic acid levels in the plasma membrane of tissue samples were analyzed by capillary gas chromatography. The levels of PGE2 were significantly higher in gliomas (n = 10) and meningiomas (n = 7) compared with control tissues (P = 0.000 and P = 0.000, respectively). Also, PGE2 levels in meningiomas were significantly higher than in gliomas (P = 0.000). Arachidonic acid levels in the plasma membrane of gliomas (n = 9) and meningiomas (n = 6) were significantly higher than in the control tissues (P = 0.000 and P = 0.000, respectively). These results suggest that the increased production of PGE2 may suppress the immune system and play an important role in tumor growth.

The prognostic importance of fibronectin and sialic acid levels in human pituitary adenomas.

In this study, fibronectin and sialic acid levels were determined in human pituitary adenomas. The mean fibronectin and sialic acid levels for human pituitary adenomas were found to be 31.64 +/- 15.82 microgram/mg protein and 21.90 +/- 9.82 microgram/mg protein, respectively, versus 6.30 +/- 2.96 microgram/mg protein and 9.88 +/- 2.81 microgram/mg protein for the normal brain tissues. Fibronectin and sialic acid levels were significantly higher (P < 0.001) in human pituitary adenomas than the normal brain tissues. In human infiltrative and non-infiltrative pituitary adenomas, the mean fibronectin and sialic acid levels were found to be 40.87 +/- 15.90 microgram/mg protein, 27.59 +/- 11.10 microgram/mg protein and 22.40 +/- 9.51 microgram/mg protein, 16.21 +/- 3.20 microgram/mg protein, respectively. Fibronectin and sialic acid levels were slightly elevated (P < 0.05) in human infiltrative pituitary adenomas compared with non-infiltrative adenomas.

Plasma fibronectin and sialic acid levels in various types of human brain tumors.

In this study, fibronectin and sialic acid concentrations were determined in plasma from patients with pituitary adenoma, meningioma and glioma, and, from controls. The mean plasma fibronectin levels in patients with pituitary adenoma, meningioma and glioma (p < 0.001) appeared to be significantly lower than controls. On the contrary, the mean plasma sialic acid values in patients with pituitary adenoma (p < 0.01), and glioma (p < 0.001) were significantly higher as compared to normal plasmas. The mean plasma sialic acid values in patients with meningioma were not different from those in controls. Also, the mean fibronectin levels in patients with glioma were found to be significantly higher than those in patients with meningioma (p < 0.05).

Fibronectin and sialic acid levels in human meningiomas and gliomas.

In this study, fibronectin and sialic acid levels have been assayed in human meningiomas and gliomas. The mean fibronectin and sialic acid levels for human meningiomas were 22.01 +/- 9.70 micrograms/mg protein and 19.58 +/- 4.89 micrograms/mg protein, respectively, and for human gliomas were 27.30 +/- 13.70 micrograms/mg protein and 25.67 +/- 11.60 micrograms/mg protein, respectively, versus 9.23 +/- 5.40 micrograms/mg protein and 13.50 +/- 4.30 micrograms/mg protein for normal brain tissues. Fibronectin and sialic acid levels were significantly higher in human meningiomas (P < 0.01 and P < 0.05) and gliomas (P < 0.001 and P < 0.01) than control group. Also the mean fibronectin and sialic acid levels were found to be 18.27 +/- 7.08 micrograms/mg protein and 17.04 +/- 6.25 micrograms/mg protein in Grade I-II and 32.60 +/- 15.00 micrograms/mg protein and 29.50 +/- 11.60 micrograms/mg protein in Grade III-IV gliomas, respectively. Fibronectin and sialic acid levels were significantly higher in Grade III-IV gliomas than Grade I-II gliomas (P < 0.05).

Glutamate receptor antagonists in experimental focal cerebral ischaemia.

Excessive activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor has been implicated in the sequence of neurochemical events in cerebral ischaemia that results in irreversible neuronal damage. The effects of the NMDA antagonist MK-801 upon the amount of ischaemic brain damage has been assessed quantitatively in a cat and in a rat model of focal cerebral ischaemia. In chloralose-anaesthetised cats, focal cerebral ischaemia was produced by permanent occlusion of one middle cerebral artery (MCA) and the animal sacrificed 6 hours later. Pretreatment with the non-competitive NMDA antagonist, MK-801 (5 mg/kg, i.v.) reduced significantly the volume of ischaemic damage in the cerebral cortex by 57% compared to vehicle-treated cats. A similar degree of neuroprotection could be demonstrated in the cat MCA occlusion model if treatment with MK-801 was initiated 2 hours after the induction of ischaemia. In halothane-anaesthetised rats, focal cerebral ischaemia was produced by permanent MCA occlusion and the animals sacrificed 3 hours later. Pretreatment with MK-801 (0.5 mg/kg, i.v.) reduced the volume of ischaemic damage in the cerebral cortex by 38%; treatment with MK-801 initiated 30 minutes after MCA occlusion was equally effective in reducing cortical damage. In contrast to calcium entry blockers such as nimodipine in the rat MCA occlusion model, the improved histopathological outcome with MK-801 is not associated with improvement in cerebral tissue perfusion to the ischaemic tissue. The increasing evidence that NMDA receptor antagonists are beneficial in experimental focal cerebral ischaemia is reviewed.

Tissue lipid composition of human gliomas and meningiomas.

This study is a comparative analysis of some lipid fractions in human brain tumors and normal brain tissue. Gliomas and meningiomas were studied and in these tumors while total lipid, total and free cholesterol and total phosphoglyceride levels were found to be significantly lower than in normal controls, the difference in esterified cholesterol levels was found to be insignificant. No significant differences in lipid fractions existed between gliomas and meningiomas except total and esterified cholesterol values.

Xanthine oxidase levels in human brain tumors.

Xanthine oxidase is most recognized for its role as the rate-limiting enzyme in nucleic acid degradation through which all purines are channelled for terminal oxidation. The enzyme serves as a source of oxygen-derived free radicals which induce both cellular injury and edema as well as changes in vascular permeability. In the study we compared xanthine oxidase levels of human brain tumors with normal brain tissues. Statistical evaluation of our results shows significantly higher xanthine oxidase levels in tumoral brain tissues. However, xanthine oxidase has not any significance for the differentiation of tumor types among each others. The oncotypes studied were meningioma and astrocytoma.

Protective effect of the glutamate antagonist, MK-801 in focal cerebral ischemia in the cat.

The effects of the glutamate N-methyl-D aspartate (NMDA) receptor antagonist, MK-801, upon ischemic brain damage has been examined in anesthetized cats. Focal cerebral ischemia was produced by permanent occlusion of one middle cerebral artery and the animal were killed 6 h later. The amount of early ischemic damage was assessed in coronal sections at 16 predetermined stereotactic planes. Pretreatment with MK-801 (5 mg/kg, i.v.), 30 min before occlusion of the middle cerebral artery significantly reduced the volume of ischemic damage (from 32.7 +/- 4.0% of the cerebral hemisphere in vehicle-treated cats to 16.2 +/- 4.5% in MK-801-treated cats). NMDA receptor antagonists that penetrate the blood-brain barrier, such as MK-801, merit further study as protective agents against ischemic brain damage.