Effect of riluzole on the acquisition and expression of amygdala kindling.

PURPOSE: Riluzole possesses various synaptic effects including an inhibitory action on glutamate release. The drug has been shown to inhibit kindled seizures, while its effect on the acquisition of kindling has not been reported. We investigated effects of riluzole on the kindling development in addition to effects on kindled seizures. METHODS: A bipolar electrode was implanted in the right amygdala of rats. Riluzole was injected intraperitoneally 30 min before kindling stimulation. To investigate effects of riluzole on the kindling development, rats were stimulated once daily for the drug session of 14 days at a current of 200 microA, 60 Hz, 1 ms for 2 s and thereafter stimulated without drugs (drug-free session) until completion of kindling. Seizure ranks and after discharge duration were observed every day. To investigate effects of riluzole on kindled seizures, fully-kindled rats were stimulated at the current of generalized seizure threshold (GST) before and after the administration of riluzole. Seizure ranks and after discharge duration were measured. GST after the treatment was also determined. RESULTS: The number of stimuli required for the first appearance of stage five seizure was significantly larger in rats treated with 8 mg/kg of riluzole than in vehicle controls. Riluzole at a dose of 8 mg/kg significantly retarded the development of seizure stages in the drug session. By comparison, effects on the duration of after discharge was relatively mild, though significantly different from the vehicle control. Riluzole at a dose of either 4 or 8 mg/kg markedly inhibited behavioral seizures and reduced the duration of after discharge in kindled seizures provoked by GST. The drug also significantly increased GST at both doses, suggesting that the anticonvulsant effects were attributed to the increase in GST. CONCLUSION: It was demonstrated that inhibitory effects of riluzole on both kindled seizures and the development of behavioral seizures in kindling acquisition with relatively mild correlation to afterdischarge duration. These effects might be attributed to inhibitory actions of riluzole on glutamate release and NMDA-receptor mediated events.

[Interleukin-6 in the cerebrospinal fluid of two patients with herpes zoster meningitis].

Interleukin-6 (IL-6) levels in the cerebrospinal fluid (CSF) and serum were measured in two immuno-competent children with herpes zoster meningitis, who had vesicles, fever, headache and vomiting before admission. The causative agent was identified as varicella zoster virus (VZV) by detecting an increased antibody index in the serum and specific DNA (by polymerase chain reaction) in the CSF. Both patients fully recovered after treatment with acyclovir. The CSF IL-6 levels were high (260.1 pg/ml, 106.1 pg/ml) at the acute stage and thereafter showed a rapid recovery. The serum IL-6 levels were normal. The increased IL-6 level in the CSF may reflect intrathecal inflammatory response following invasion of VZV into the central nervous system.

[A case of pheochromocytoma with von Recklinghausen's and review of 67 Japanese cases].

A 19-year-old woman with von Recklinghausen's disease was referred to our hospital because of right adrenal pheochromocytoma. The tumor was detected incidentally with the abdominal ultrasonography when she complained epigastralgia to the home doctor who treated her hypertension. Plasma and urinary catecholamines level were elevated. The tumor was removed by laparoscopy assisted adrenalectomy without pneumoperitoneum. The resected specimen was 35 x 60 x 75 mm in size and weighed 70 g. Pathological diagnosis was adrenomedullary pheochromocytoma. Postoperative course was uneventful. She has been well with no signs of recurrence after 7.5 years. We reviewed 67 Japanese patients previously reported as von Recklinghusen's disease with pheochromocytoma. Of the 60 patients whose details were described, 16.7% had metastases and pathological malignancy from pheochromocytoma.

Lack of substantial effect of the H(3)-antagonist thioperamide and of the non-selective mixed H(3)-antagonist/H(1)-agonist betahistine on amygdaloid kindled seizures.

We investigated whether some histamine H(3)-antagonists would attenuate amygdaloid kindled seizures in rats. Thioperamide, a standard H(3)-antagonist, did not significantly reduce either seizure ranks or afterdischarge duration (ADD). Betahistine which has both H(3)-antagonistic activity and H(1)-agonistic activity significantly reduced ADD, albeit mild at a toxic dose, though seizure ranks were not affected. In addition, L-histidine, the precursor of histamine, affected neither seizure ranks, nor ADD. It was shown that H(3)-antagonists have no significant inhibitory action against amygdaloid kindled seizures, probably because released histamine was unable to inhibit those seizures.

Functional characterization of renal chloride channel, CLCN5, mutations associated with Dent'sJapan disease.

BACKGROUND: The annual urinary screening of Japanese children above three years of age has identified a progressive renal tubular disorder characterized by low molecular weight proteinuria, hypercalciuria and nephrocalcinosis, and this represents a variant of Dent's disease. Hitherto, 12 mutations of the X-linked renal specific chloride channel, CLCN5, have been reported in the Dent'sJapan variant. To further identify such CLCN5 mutations and to define the structure-function relationships of this channel, we have investigated five unrelated, non-consanguinous Japanese families with this disorder. METHODS: Leukocyte DNA from probands was used with CLCN5 primers for PCR amplification of the coding region, and the DNA sequences of the products determined. Functional studies were performed by expressing the mutants in Xenopus oocytes. RESULTS: Five CLCN5 mutations consisting of two nonsense (R648X and R704X), two missense (S270R and L278F) and one acceptor splice site mutation (ag-->cg) in intron 4 were identified. The missense and splice site mutations represent novel abnormalities. Heterologous expression in Xenopus oocytes of wild-type and the missense mutants demonstrated that the mutations, which were translated, either abolished or markedly reduced chloride conductance. CONCLUSIONS: These results expand the spectrum of CLCN5 mutations associated with this renal disorder and provide insight into possible structure-function relationships. For example, both the missense mutations are located within a short putative loop between two transmembrane domains, and our results suggest that this region may have an important functional role in the regulation of channel activity.

[A case of encephalitis due to Mycoplasma pneumoniae: detection of specific DNA from cerebrospinal fluid and elevation of interleukin-6].

A 9-year-old female was admitted to our hospital due to a generalized seizure and consciousness disturbance. The patient had a fever and rash four days before admission, but she had no respiratory symptoms. The seizure and consciousness disturbance was prolonged and intractable. We diagnosed the patient as having encephalitis because of the increase in the cell count in the cerebrospinal fluid (CSF) and a diffuse slow EEG wave. The computed tomography of the head was normal. The causative agent was identified as Mycoplasma pneumoniae because of the increase of antibodies, and the detection of a specific DNA with a polymerase chain reaction. The interleukin (IL)-6 level of CSF was high (384 pg/ml). In spite of intensive treatment she had severe neurological sequelae. The invasion of Mycoplasma pneumoniae to the central nervous system appeared to have a role in the development of encephalitis in the patient. We speculated that there is a possible relationship between the IL-6 levels of CSF and clinical severity of encephalitis.

Effects of acute treatment and long-term treatment with MK-801 against amygdaloid kindled seizures in rats.

Effects of both acute and long-term treatments with a non-competitive NMDA-antagonist, MK-801, were studied in rats in order to investigate whether NMDA receptors would be involved in the maintenance of kindling. Intraperitoneally administered MK-801 at doses of 0.5, 1.0 and 2.0 mg/kg inhibited fully amygdaloid kindled seizures (stage 5) behaviorally and significantly reduced the duration of after discharge and postictal spikes in a dose-dependent manner. Long-term (28 days) administration of MK-801 at three dosages neither abolished behavioral kindled seizures nor significantly altered generalized seizure thresholds. However the after discharge duration and postictal spikes were significantly reduced in rats treated with MK-801 at doses of 0.5 and 1.0 mg/kg, while no significant alterations were observed in rats treated with saline or MK-801 at a dose of 2.0 mg/kg. Acute effects of MK-801 suggested that NMDA receptors were involved in the maintenance of kindling. On the other hand, long-term treatments with MK-801 remained to show such an unequivocal effect.

[A case of renal pelvic cancer associated with giant hydronephrosis of a horseshoe kidney].

A 71-year-old woman with loss of appetite was referred to our hospital. Imaging diagnosis revealed a large, cystically dilated left kidney with a solid tumor inside the cavity and right hydronephrosis. A chest X-ray revealed multiple metastatic lesions. A horseshoe kidney was found intraoperatively and left nephroureterectomy with partial cystectomy was performed. Histological diagnosis was poorly differentiated transitional cell carcinoma. She died of progressive pulmonary metastases 2 weeks after operation. This is the 19th case of a renal pelvic tumor associated with a horseshoe kidney reported in the Japanese literature. The diagnosis was confounded by the extreme dilation and deformity of the hydronephrotic kidney.

Nasal mucosal thickening simulating a tumor: potential for misdiagnosis in brain perfusion imaging.

A 33-year-old, female presenting with dementia was admitted to our institution. Except for slight muscle atrophy noted on both lower extremities there were no other significant physical signs or laboratory findings. Since initial Tc-99m HMPAO SPECT showed hypoperfusion on both temporal, parietal and occipital lobes, follow up study with the same radiotracer was done. Increase in uptake was noted in the left side of the face. There was no abnormality noted on ENT examination. CT scan and MRI showed slight nasal mucosal wall thickening. T1-201 SPECT showed increased uptake in the nasal area. The increase in uptake could be due to nasal mucosal thickening. This could simulate nasal tumor and interfere in determining ROI for brain perfusion studies.

[Two successful deliveries within four years after cadaveric kidney transplantation: a case report].

A woman successfully delivered two children after cadaveric kidney transplantation. She received a kidney graft at the age of 18 years because of end-stage renal failure due to chronic glomerulonephritis. Eighteen months after surgery, she became pregnant. As she was receiving immunosuppressive therapy with cyclosporin, azathioprine, mizoribine and prednisolone, we discontinued mizoribine. The child was delivered by a caesarean section in week 30 of gestation. Both the increase of liver enzymes and the decrease of creatinine clearance were slight and transient. She successfully delivered another child just a few days before the 4th anniversary of her kidney transplantation. Including this patient, we have experienced 11 deliveries by women bearing kidney grafts. Intensive joint management with the obstetric service is necessary to achieve successful delivery without losing the graft.

[Influence of pneumoperitoneum on respiratory function during urological laparoscopic surgery].

PURPOSE: To determine the influence of pneumoperitoneum on respiratory function during urological laparoscopic surgery. MATERIALS AND METHODS: We performed laparoscopic surgery on 82 patients, 45 of these patients were examined in detail of the effect of pneumoperitoneum on the respiratory function. Of these 45 patients, 14 patients received lymphadenectomy and 31 patients received adrenalectomy. For comparative analysis, 4 patients with laparoscopic cholecystectomies were also examined. Under general anesthesia, carbon dioxide tension (PaCO2) was analyzed before, during, and after the pneumoperitoneum. The data were analysed along with 4 factors; the patient's spirographic parameters, alveolar-arterial gas difference (AaDO2), insufflation pressure for the pneumoperitoneum, and operating time. RESULT: After starting the pneumoperitoneum, PaCO2 levels rose significantly. The PaCO2 levels of patients underwent laparoscopic adrenalectomy were higher than that of patients underwent laparoscopic cholecystectomy. The preoperative vital capacity and forced expiratory volume in one second (FEV1.0) did not show a significant difference of increase in the degree of PaCO2 increase. In contrast, the important factors that were closely related to the elevation of PaCO2 were preoperative AaDO2 and intraoperative insufflation pressure. Patients with high preoperative AaDO2 (> 10 torr) showed a significant increase in PaCO2 levels after pneumoperitoneum. When insufflation pressure was high (> = 10 mmHg), there was a significant rise of PaCO2 after pneumoperitoneum. In all patients whose operating time was 300 minutes or more, high levels of PaCO2 continued on the next day after surgery. CONCLUSION: We should still carefully observe the insufflation pressure, operating time, and other ventilation conditions during laparoscopic surgery.

Simultaneous monitoring of the seizure-related changes in extracellular glutamate and gamma-aminobutyric acid concentration in bilateral hippocampi following development of amygdaloid kindling.

We simultaneously monitored the seizure-related changes in extracellular hippocampal glutamate (Glu) and gamma-aminobutyric acid (GABA) concentration in brain dialysates in order to clarify the role of Glu and GABA in the development of kindling. Brain dialysates were collected every 5 min from 10 min prior to 80 min after stimulus in the three developing conditions consisting of pre-kindling state, stage 3 (C-3), and five consecutive stage 5 (5*C-5) following kindling in the same rat. Extracellular Glu level increased rapidly, lasting for only 5 min after stimulus. The post-stimulus ratio of Glu increase in partially kindled rats (C-3) was 2.5-3.5 times of the baseline, and in fully kindled rats it was about 5 times of the baseline. Extracellular GABA concentration enhanced gradually, reaching a plateau level at 15-20 min and lasting for several hours after stimulus at each stage. The enhancement of GABA level was about 1.5 times of the baseline in partially kindled stage, and was about 2.5 times of the baseline in fully kindled stage. There was no significant difference between the two hemispheres with respect to either the time-course or the magnitude of Glu and GABA increase respectively. These data show that progressive, transient and stimulus-induced enhancement of extracellular Glu levels combined with long-lasting elevation of extracellular GABA levels in the bilateral ventral hippocampi results in imbalance between the excitatory and inhibitory neuronal systems, causing excessive propagation of seizure activity, culminating in the secondary generalized seizure of amygdaloid kindling.

Association of DQB1*0302 alloantigens in Japanese pediatric patients with steroid-sensitive nephrotic syndrome.

We identified human leukocyte alloantigens (HLA) class II alleles in 24 Japanese children with steroid-sensitive nephrotic syndrome (SSNS) by deoxyribonucleic acid (DNA) typing. The DQA1 and DQB1 alleles were identified using sequence-specific oligonucleotide probes for DQA and DQB. The frequency of DQB1*0302 was significantly higher in the patients than in the controls (54.0 vs. 16.0%, respectively; relative risk, RR = 6.2; pc < 0.00009. We also found that the frequency of DQA1*0103 in the patients was significantly lower than in the controls (RR = 0.194, pc < 0.04). Several studies have identified an association between certain HLA by serotyping. In the present study, we investigated the HLAs of Japanese patients with SSNS by DNA typing and observed a significant increase in the frequency of DQB1*0302 in patients with the disease. HLA-DQ3, which was proven to be associated with SSNS, consists of HLA DQ7, 8 and 9. DQB1*0302 is a component of HLA-DQ8. So we proposed the increase of DQ3 was due to an increase in DQ8.

Comparison of asymptomatic and symptomatic childhood glomerulonephritis progressing to renal failure: a report of Kyushu Pediatric Nephrology Study Group.

We evaluated the clinicopathological features and the outcome of 33 children with primary glomerulonephritis (GN) as the cause of renal failure; 17 had asymptomatic (ASP) haematuria and/or proteinuria and the remaining 16 had symptoms suggestive of GN. The renal histology in the ASP group indicated IgA GN in 6 children, focal segmental glomerular sclerosis (FSGS) in 4, diffuse proliferative GN (DPGN) in 3, membranous GN (MGN) in 1, membranoproliferative GN (MPGN) in 1 and diffuse sclerosing GN in 2. In the symptomatic (SYP) group, FSGS was evident in 9 children, DPGN in 3, MGN in 2, IgA GN in 1 and MPGN in 1. There was no difference in the histological severity between the two groups. Fourteen children in the SYP group had nephrotic syndrome (NS) and/or hypertension at their initial visits. Only 4 children in the ASP group showed NS or hypertension during the period of follow-up. Eleven children in the ASP group and all in the SYP group were treated with immunosuppressive and/or antihypertensive drugs, but these did not improve the prognosis of the ASP children compared with those in the SYP group. There was no significant difference in the mean duration between the onset of the disease and the start of dialysis in these two groups. In conclusion, it is questionable whether the urinary mass screening programme in Japan will alter the outcome of children with GN.

Bilateral seizure-related changes of extracellular glutamate concentration in hippocampi during development of amygdaloid kindling.

To monitor the seizure-related changes of extracellular hippocampal glutamate (Glu) concentration during the development of amygdaloid kindling, we used brain dialysates and an enzymatic cycling technique for Glu determination with a highly sensitive assay and high time resolution (1 min). The extracellular Glu level was transiently (for 3 min) enhanced after stimulus and returned rapidly to baseline. In partially kindled rats (stage 3), the extracellular Glu level during the first minute post stimulus was 2.5-3.5-fold that of baseline, while fully kindled rats exhibited about a 5-fold increase in Glu level. Amygdaloid kindling is accompanied by a progressive, transient, stimulus-induced enhancement of extracellular Glu levels during the first minute post stimulus in both hippocampi.

Effect of subject's family name on visual event-related potential in schizophrenia.

Visual event-related potentials (ERPs) were recorded from 15 schizophrenics and 15 age-matched and gender-matched controls, while they performed a modified version of the oddball paradigm. Each subject was required to detect target stimuli among a random sequence of stimuli under two conditions, name and color. In the name condition the stimulus sequence consisted of the subject's family name (deviant 18%), four other family names (standard 73%), and a city name (target 9%). In the color condition the respective stimuli were a pair of solid red circles, four white paired-arrows, and a pair of white plus and minus signs. ERPs elicited by stimuli contained triphasic potentials of P2, N2, and P3. In controls these waves were selectively enhanced for the subject's family name as compared with standards, whereas in schizophrenics no significant difference between the subject's family name and other names was observed. In contrast, selective enhancement for color deviants was observed in both subject groups. These results suggest that impairment of involuntary attention, especially for familiar and significant stimuli such as names in daily life, may underlie disturbances of attentionally controlled central processing in schizophrenia.

Effect of unilateral dentate nucleus lesions on amygdaloid kindling in rats.

Amygdala kindling is used to investigate cerebellar dentate nucleus participation in the neuronal plasticity of the cerebrum. We studied the behavioral change, the occurrence of epileptiform events, and the duration of afterdischarge during amygdaloid kindling under control conditions and after a dentate lesion of the contralateral cerebellum. Our results indicate that the dentate lesion induced the facilitation of the behavioral development of the amygdaloid kindling, whereas there was only a slight increase in the duration of afterdischarge and the spontaneous epileptiform potential of the amygdala. There was a discrepancy between the behavioral kindling and the electroencephalographic epileptic activity. Therefore the dentate lesion must play a role in controlling the generalization mechanism of epilepsy. We also found that on a right amygdala that had been influenced by a left dentate lesion there were few spikes, while on the left amygdala there were frequent spikes. These results suggest that the dentate nucleus plays an important role in amygdaloid kindling as well as in the neuronal plasticity of the amygdala.

Epidemiologic survey of children with end-stage renal disease.

We performed an epidemiologic study on the basis of a questionnaire survey of 162 children with end-stage renal disease (ESRD). Sixty-nine (43%) of our 162 children, including 25 detected at mass screening of urine, were found by chance hematuria and/or proteinuria. The three major causes of ESRD in our children were chronic glomerulonephritis (CGN) in 56, congenital anomalies of the urinary tract in 30, and nephrotic syndrome (NS) in 27. The renal pathology in 39 children with CGN or NS was focal glomerular sclerosis in 15, diffuse mesangial GN in 7, IgA GN in 5, membranoproliferative GN in 3, membranous GN in 3, and unclassified in 6. Forms of dialysis initiated were hemodialysis in 91 children, continuous ambulatory peritoneal dialysis (PD) in 66, and intermittent PD in 5. Renal transplantation was performed on 38 children, and the graft and the patient survival rates were 76% and 89%, respectively. The survival rate of our 162 children for a mean follow-up of 8.1 years was 77%. In conclusion, an integrated program of maintenance dialysis and transplantation provides a favorable life for children with ESRD.