Surgical Treatment of Intractable Seizures Due to Hypothalamic Hamartoma

Summary: A 6.5-year-old boy developed seizures at age 2.8 years consisting of episodes of unconsciousness and laughing attacks. By age 6 years, multiple seizure types, including generalized tonic-clonic (GTC), complex partial (CPS) and akinetic seizures, and drop attacks were occurring several times daily. EEG showed multifocal epileptic discharges. Antiepileptic drugs (AEDs) did not control the seizures. With progression of the epilepsy, cognitive deterioration developed. There were no manifestations of precocious puberty. Neuroimaging disclosed a suprasellar mass in continuity with the hypothalamus, and a diagnosis of hypothalamic hamartoma was made. After surgical resection of the hamartoma, the seizures were completely alleviated, and the epileptic EEG discharges disappeared. Improvement of mental function was also noted.     

Non-prostanoid thromboxane A2 receptor antagonists with a dibenzoxepin ring system. 2.

A series of 11-[2-(1-benzimidazolyl)ethylidene]-6,11-dihydrodibenz[b,e]oxep in-2- carboxylic acid derivatives and related compounds were synthesized and found to be potent TXA2/PGH2 receptor antagonists. Each compound synthesized was tested for its ability to displace [3H]U-46619 binding from guinea pig platelet TXA2/PGH2 receptors. Structure-activity relationship studies revealed that the following key elements were required for enhanced activities: (1) an (E)-2-(1-benzimidazolyl)ethylidene side chain in the 11-position of the dibenzoxepin ring system and (2) a carboxyl group in the 2-position of the dibenzoxepin ring system. The studies also indicated that the TXA2/PGH2 receptor binding affinities of this series of compounds in guinea pig platelet were poorly correlated with those in human platelet. Introduction of substituent(s) to the benzimidazole moiety was effective and sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)ethylidene]- 6,11-dihydrodibenz[b,e]oxepin-2-carboxylate monohydrate (57) recorded the highest affinity for human platelet TXA2/PGH2 receptor with a K(i) value of 1.2 +/- 0.14 nM. It demonstrated potent inhibitory effects on U-46619-induced guinea pig platelet aggregation (in vitro and ex vivo) and human platelet aggregation (in vitro). Compound 57, now designated as KW-3635, is a novel, orally active, and specific TXA2/PGH2 receptor antagonist with neither TXA2/PGH2 receptor agonistic nor TXA2 synthase inhibitory effects. It is now under clinical evaluation.     

Typing of methicillin-resistant Staphylococcus aureus by antibiotic resistance phenotypes as an epidemiological marker in nosocomial infections]

A total of 129 clinical isolates of methicillin-resistant Staphylococcus aureus was tested for the susceptibility to 28 antibiotics, antiseptics and heavy metal salts, according to the method of Gillespie et al. The strains showed resistance ranging from 20% to 80%, to 10 agents, such as amikacin, chloramphenicol, clindamycin, gentamicin, neomycin, streptomycin, tobramycin, acriflavine, cadmium nitrate, ethidium bromide. These agents were finally chosen for typing in this study. Strains resistant to 10 agents were distributed into 55 phenotypes. Most strains isolated from one ward belonged to the specified phenotype, whereas strains isolated from other wards were divided into a variety of phenotypes. It seemed to be the occurrence of nosocomial infection in this hospital. This typing method gives the merit to be easy, economical, rapid and reproducible for the epidemiological investigations in the clinical bacteriological laboratory.     

Somatosensory and spinal evoked potentials in patients with cervical syringomyelia.

We recorded somatosensory evoked potentials (SEPs) from the skin surface and spinal evoked potentials (SpEP) from the posterior epidural space after median nerve stimulation in 11 patients with cervical syringomyelia. We compared SEPs with SpEP to assess the possible feasibility of using these techniques to localize the offending lesion. SEP abnormalities were present on one or both sides of 7 patients (9 of 22 upper limbs; 41%). The abnormal SEP pattern was the attenuation or loss of N13, which was of little value for delineating the lesion. In patients with abnormal SEPs, three types of abnormal SpEPs were noted. In the Type A abnormality (three limbs), potentials were attenuated in all cervical segments, suggesting that the syrinx itself had enlarged to involve the posterior column. In Type B (two limbs), there was reduced amplitude or absent upper cervical potentials, probably a result of the accompanying tonsilar herniation. Finally, the Type C (four limbs) abnormality was a mixture of Type A and B abnormalities in that the attenuated cervical potentials were again affected in the most upper cervical segment. We concluded that SpEP revealed various kinds of involvement of the dorsal column pathway in the syringomyelic patients, a finding not expressed with conventional SEPs.     

Radical correction of paracardiac type IIb of total anomalous pulmonary venous connection using pedicled flaps of right atrium and atrial septum

Surgical results of total anomalous pulmonary venous connection (TAPVC) has been improved in recent years, however, late development of pulmonary venous obstruction was our concern in its total correction in early infancy. In the cardiac type of TAPVC, in which the pulmonary veins were connected to the right lateral wall, prosthetic patch is conventionally used in diversion of pulmonary venous flow into left atrium. It seemed favorable to repair this subset without using prosthesis. A 3-month-old female with TAPVCIIb according to Darling's classification underwent total correction on September 22th, 1988. Two pedicled flaps were developed using the right atrial wall and the atrial septum to create a pulmonary venous channel to divert arterial blood into left atrium and absorbable sutures were used throughout. Right atrium was entered through a vertical incision in its body and all the pulmonary veins were found in a recess in the lateral wall of the right atrium. Atrial septal defect in the cranial aspect of the fossa ovalis was enlarged by cutting the primum tissue along the right limbus and its caudal margin so as to form a pedicled flap attached to the left limbic tissue. Then the flap was sutured along the limbus to create a roof of the fossa ovalis. The second flap was made in the middle of the lateral atrial wall and was used to create a tunnel from the recess to the atrial septal defect. The defect in the right atrial wall was closed directly and no prosthetic patch was used. Postoperative course was uneventful and echocardiogram showed wide pulmonary venous channel draining into the left atrium.     

Migraine is associated with enhanced arterial stiffness.

Migraine is a common subtype of headache. Epidemiological studies have revealed that migraine could be an independent risk factor for ischemic stroke even in elderly subjects. Arterial stiffness is one of the major pathophysiological bases of stroke. In the present study, we cross-sectionally investigated the possible relationship between migraine and arterial stiffness in community-dwelling subjects. The study subjects were independently recruited from two sources (Group A, n=134, 68+/-5 years; Group B, n=138, 68+/-7 years). Augmentation index (AI), the ratio of augmented pressure by the reflection pressure wave to the pulse pressure, was obtained from the radial arterial waveform as an index of arterial stiffness. Brachial blood pressure was also measured simultaneously. Migraine was diagnosed using a previously validated questionnaire. The prevalence of migraine was 5.2% (Group A) and 16.7% (Group B). Subjects with migraine had higher radial AI in both Group A (migraine, 101+/-15%; other headache, 88+/-12%; no headache, 86+/-12%, p=0.003) and Group B (95+/-11%, 90+/-11%, 91+/-14%, p=0.058). Multiple linear regression analysis revealed that migraine was an independent determinant of AI (beta=0.154, p=0.002) after adjustment for other confounding factors: age (beta=-0.024, p=0.654); sex (beta=0.141, p=0.069); body height (beta=-0.215, p=0.005); systolic blood pressure (beta=0.174, p=0.001); medication for hypertension, hyperlipidemia, and diabetes mellitus (beta=-0.014, p=0.787); and heart rate (beta=-0.539, p<0.001). In a separate analysis by sex, migraine was also a significant determinant for AI (male, beta=0.246, p=0.019; female, beta=0.159, p=0.008). Migraine in the elderly could be a clinical manifestation of enhanced arterial stiffness.     

Pharmacologic preconditioning effects: Prostaglandin E1 induces heat-shock proteins immediately after ischemia/reperfusion of the mouse liver

Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilation, and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion injury in vivo using a complementary DNA microarray. PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 minutes and then reperfused. Livers were harvested 0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays. Serum alanine aminotransferase and aspartate aminotransferase levels at 180 minutes postreperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and glutathione S-transferase were upregulated at the end of the ischemic period (0 minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1 induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an important role in the protective effects of PGE1 against ischemia/reperfusion injury of the liver.     

Susceptibility of neonatal lipoproteins to oxidative stress

We compared peroxidizability of neonatal and adult lipoproteins exposed to oxidative stress initiated by an azo-compound. Oxygen uptake showed a two-phase pattern, with slow oxygen uptake in the first phase and faster uptake in the second phase. During the first phase, tocopherol was consumed progressively, inhibiting lipid peroxidation by scavenging peroxy radicals. After the tocopherol concentration fell below a critical level, extensive propagation of chain oxidative reactions produced the rapid oxygen uptake in the second phase. In the first phase of neonatal lipoprotein oxidation, a faster oxygen uptake was observed and the length of this phase was shorter than in adults. The oxygen uptake rate in the second phase was smaller in the neonatal lipoproteins. In other words, neonatal lipoproteins were more susceptible to oxidative stress than were adult ones when tocopherol remained in lipoproteins, but after tocopherol depletion the reverse was true. These results were consistent with the finding that in neonatal lipoproteins the tocopherol/lipid ratio was significantly lower (length of the inhibitory phase was closely correlated to the lipoprotein tocopherol content). In addition, the average number of active bisallylic hydrogen atoms, which are considered to determine the relative susceptibility of polyunsaturated fatty acids to oxidation, was significantly smaller (oxygen uptake rate in the second phase was closely correlated to the active bisallylic hydrogen number) in neonatal lipoproteins, and the ratio of active bisallylic hydrogen to tocopherol content (which closely correlated to oxygen uptake rate in the first phase) was also significantly lower compared with the adult ratio. Under physiologic conditions, an intensive oxidation of lipoproteins sufficient to cause lipoprotein tocopherol to fall below critical levels is unlikely to occur.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of submental stimulation for several consecutive nights in patients with obstructive sleep apnoea.

BACKGROUND--It has previously been reported that short term submental stimulation can reduce the frequency of apnoea and improve sleep architecture in patients with obstructive sleep apnoea. The effects of submental stimulation during consecutive nights on apnoea or on daytime sleepiness have not, however, been studied. METHODS--Patients with obstructive sleep apnoea were studied by polysomnography on a control night, for five consecutive nights of submental stimulation, and on three following nights (n = 8). A multiple sleep latency test (MSLT) (n = 8) and measurement of the upper airway resistance (n = 5) were performed during the day after the polysomnographic study, on the control night, and on the fifth stimulation night. In an additional five patients with obstructive sleep apnoea, matched for age, sex, and weight, the effects of two nights of stimulation were examined for comparison. Submental stimulation began when an apnoea lasted for five seconds and stopped with the resumption of breathing as detected by oronasal flow. RESULTS--The apnoea index, the number of times per hour that SaO2 dropped below 85% (SaO2 < 85%/hour), and the total apnoea duration expressed as a percentage of total sleep time during stimulation nights decreased to approximately 50% of the corresponding values on the control night. This improvement persisted for at least two nights after the five consecutive stimulation nights, but not after the two consecutive stimulation nights. Sleep architecture and MSLT following the stimulation nights improved but upper airway resistance did not change. CONCLUSIONS--Submental stimulation for five consecutive nights in patients with obstructive sleep apnoea improved the breathing disturbance, sleep quality, and daytime sleepiness. The effect lasted for the following two nights, but did not completely abolish the sleep disordered breathing.