Soluble vascular endothelial growth factor receptor-1 is reduced in patients with resistant hypertension after renal denervation.

Renal denervation (RDN) has been shown in several studies to reduce blood pressure (BP) in patients with resistant hypertension (RH). Data on potential biomarkers associated with BP changes remain scarce. We evaluated whether soluble vascular endothelial growth factor receptor (sVEGFR-1) is affected by the procedure. A total of 57 patients with RH participated in this study. BP and heart rate were recorded at baseline and at 3 months follow-up, at which time blood samples were collected to determine the levels of sVEGFR-1, VEGF-A, VEGF-C, nitric oxide (NO), soluble vascular adhesion molecule 1 and soluble intracellular adhesion molecule 1. None of the biomarkers had a predictive value that could identify responders vs non-responders to RDN. However, sVEGFR-1 concentration was dramatically reduced after RDN (5913±385 vs 280±57 pg ml-1, P<0.001). At the same time VEGF-A levels were significantly increased (10.0±3.0 vs 55.5±7.9 pg ml-1, P<0.001), without significant changes in VEGF-C. NO levels were significantly increased after RDN in the whole group (82.6±6.2 vs 106.9±7.8 µM, P=0.021). Interestingly, the elevation in NO levels at 3 months was only seen in patients who demonstrated a reduction in systolic BP of ⩾10 mm Hg (78.9±8.3 vs 111.6±11.7 µM, P=0.018). We report a significant reduction in sVEGFR-1 levels after RDN procedure, which was accompanied by a significant increase in VEGF-A concentration as well as NO. Changes in plasma cytokines were not quantitatively linked to magnitude of BP reduction. An RDN-induced reduction in sVEGFR-1 plasma levels and increase in VEGF-A would raise the VEGF-A/sVEGFR-1 ratio, thereby increasing VEGF-A bioavailability to act on its full-length receptor and may contribute to the BP-lowering effect potentially via NO-mediated pathways.

Central vagal activation by alpha(2) -adrenergic stimulation is impaired in spontaneously hypertensive rats.

AIM: To elucidate the abnormality of vagal control in spontaneously hypertensive rats (SHR) by measuring left ventricular myocardial interstitial acetylcholine (ACh) release in response to α(2) -adrenergic stimulation as an index of in vivo vagal nerve activity. METHODS: A cardiac microdialysis technique was applied to the rat left ventricle in vivo, and the effect of α(2) -adrenergic stimulation by medetomidine or electrical vagal nerve stimulation on myocardial interstitial ACh levels was examined in normotensive Wistar-Kyoto rats (WKY) and SHR under anaesthetized conditions. RESULTS: Intravenous medetomidine (0.1 mg kg(-1) ) significantly increased the ACh levels in WKY (from 2.4 ± 0.6 to 4.2 ± 1.3 nmol L(-1) , P < 0.05, n = 7) but not in SHR (from 2.5 ± 0.7 to 2.7 ± 0.7 nmol L(-1) , n = 7). In contrast, electrical vagal nerve stimulation increased the ACh levels in both WKY (from 1.0 ± 0.4 to 2.9 ± 0.9 nmol L(-1) , P < 0.001, n = 6) and SHR (from 0.9 ± 0.2 to 2.2 ± 0.4 nmol L(-1) , P < 0.001, n = 6). Intravenous administration of medetomidine (0.1 mg kg(-1) ) did not affect the vagal nerve stimulation-induced ACh release in either WKY or SHR. CONCLUSION: Medetomidine-induced central vagal activation was impaired in SHR, whereas peripheral vagal control of ACh release was preserved. In addition to abnormal sympathetic control, vagal control by the central nervous system may be impaired in SHR.

Microleakage of self-etching primers after thermal and flexural load cycling.

PURPOSE: To evaluate the adhesive properties of a one-bottle self-etching primer system. MATERIALS AND METHODS: 150 wedge-shaped cervical cavities on bovine teeth were restored with Clearfil Liner Bond 2 (LB), Clearfil Liner Bond 2V (LV) or Clearfil SE Bond (SE), according to the manufacturer's instructions. Twenty specimens of each adhesive system were finished 15 mins after light curing and 30 specimens were finished after a 24-hr storage period in water. From each group, 10 restorations were immediately immersed in 0.5% basic fuchsin solution and kept there for 24 hrs to examine microleakage. The other 10 restorations were thermocycled (5-60 degrees C, 15 s dwell time, 5,000 cycles), and then immersed in the dye solution. The remaining 10 specimens of the 24-hr storage group were subjected to flexural load cycling (0.5 mm labio-lingual displacement at the incisal edge, 10,000 cycles, 1 cps) prior to immersion in the dye solution. The data was analyzed using the Mann-Whitney U-test and the Kruskal-Wallis test. The tensile bond strengths of the adhesive systems to bovine enamel and dentin were also determined. The data was analyzed using the Student's t-test and ANOVA. In addition, SEM examinations were made to evaluate the effects of self-etching primers on enamel and dentin surfaces. RESULTS: LV and SE showed significantly better marginal sealing than LB (P<0.05). The marginal integrity of SE did not deteriorate even after immediate finishing, thermal stresses or flexural loads. There were no significant differences in bond strengths among the adhesive systems tested. All adhesive systems showed similar bond strengths to enamel and dentin. The enamel etching patterns using LV and SE systems were obscure and difficult to assess. Although the smear plugs were not fully removed, no smear layer was observed on the treated dentin surfaces, regardless of the self-etching primer system used. CLINICAL SIGNIFICANCE: Clearfil SE bond could possibly improve the clinical performance of cervical cavities.

The effect of flexural load cycling on the microleakage of cervical resin composites.

Although several in vitro studies have attempted to investigate the microleakage of Class V resin composites under loading, the effect of load cycling on marginal seal is still unclear. This may be due to the fact that axial loads were applied to the specimens. This study investigated the effect of flexural loads on marginal sealing of cervical resin composites. One hundred and fifty cervical wedge-shaped cavities were restored with Clearfil Photo Bond, Clearfil Liner Bond 2, Scotchbond Multi-Purpose with 10% maleic acid, Scotchbond Multi-Purpose with 35% phosphoric acid or Mac-Bond 2 according to the manufacturers' instructions. After the restorations were finished, 10 specimens from each group were immersed in 0.5% basic fuchsin solution to examine microleakage. Prior to dye solution immersion, 20 specimens were subjected to flexural load cycling (1 mm labio-lingual or linguo-labial displacement at the incisal edge, 10,000 cycles, 1 cycle/second). The data were analyzed using the Kruskal-Wallis test and the Mann-Whitney U-test (p<0.05). When the flexural loads were not applied, both the incisal and apical margins showed good marginal sealing, regardless of the adhesive system used. Labio-lingual loading significantly deteriorated the marginal integrity at the incisal enamel margins, except for those restored with Clearfil Photo Bond. However, only Clearfil Photo Bond demonstrated a significant increase in microleakage along the apical dentin margins. Linguo-labial loading had no significant effect on the marginal seal.

[Developmental changes of awareness during passive and active attentions: evaluation of serial event-related potentials (N130, N180, P250)].

Serial event-related potentials (ERPs), especially the negative components before P300, were recorded to evaluate the developmental changes of awareness, or intentional attention. In this study, 36 healthy children (5-16 years of age) and eight healthy adults (19-37 years) were told to perform two attentive paradigms: passive and active. Each test condition consisted of 16 electrical stimuli. Four trials were averaged in sequence and then evaluated as serial four blocks. With repetition in both passive and active attentive paradigms the amplitude of N130 was not attenuated until six years old. During active attention, N180 remained undiminished in adolescents and adults. The amplitude of P250 decreased with repetition during passive attention in children over seven years old, but was not attenuated during active attention in adults. These results suggest that N130 reflects the orienting reflex, and that N180 is associated with the process to maintain awareness.

[Quantitative measurement of prefrontal lobe volume on three dimensional magnetic resonance imaging scan].

This article describes the measurement of the frontal and prefrontal lobe volumes on three dimensional (3-D) MRI in 13 children aged 5 months to 14 years and in 3 adults aged 27 to 39 years. The 3-D MRI data were acquired by the fast spoiled gradient recalled (SPGR) sequence using a 1.5 T MR imager. The frontal and prefrontal lobe volumes were measured by the volume measurement function of the Workstation. We confirmed that this technique to analyze segmental brain volumes achieved acceptable levels of reliability and accuracy. There was an increase in the frontal and prefrontal lobe volumes with advancing age, being rapid between 8 and 15 years of age. The prefrontal to frontal lobe volume ratio also increased gradually, with spurts between 8 and 15 years of age. This approach may be particularly useful for studies on patients with frontal and prefrontal lobe dysfunctions.

[Evaluation of nasal obstruction with acoustic rhinometry: a simulated study with a nasal model].

The measurement of nasal resistance is important for understanding the pathophysiology of nasal obstruction. However, it is difficult to define the normal range of nasal resistance because of various physiological factors. Several authors have reported that nasal resistance is not correlated with the sensation of nasal obstruction. On the other hand, acoustic rhinometry was introduced by Hilberg et. al. (1989) to determine the geometry of the nasal cavity. The method based on sound reflection analysis provides an estimate of the cross-sectinal area of the nasal cavity as a function of the distance from the nostril. Recently, the measurement by acoustic rhinometry is becoming popular also in our country. However, the assessment by acoustic rhinometry may be different from that by measuring nasal resistance because the cross-sectional area is measured without studying the air flow. The aim of this study was to investigate the benefit of acoustic rhinometry using a nasal model. First, 4 pieces of nasal model LM005 (KOKEN, Co., Japan) made of silicone were coated with resinous putty. Then, the changes in the area-distance curve were measured with an acoustic rhinometer RHIN 2100 (SRE, Co., Denmark) in which this putty was scraped off gradually from anterior to posterior. In the next study, the quality of coated putty was increased at three points of the nasal area: anterior part, middle part, and posterior part. Thereafter the changes in the area-distance curve were observed in the same way. As a result, neither a decrease or an increase in the putty changed the area-distance curve at the posterior part. Therefore, it is suitable that the degree of the changing of nasal mucosa is defined as the change in the nasal volume between the top the I-notch and the end of the C-notch. In conclusion, acoustic rhinometry is useful to investigate nasal obstruction, especially the change in the nasal mucosa. Therefore, further clinical study is required for the different purpose of measuring nasal resistance.

[Electrophysiologic evaluation of passive and active attentions--I. Topographic analysis of somatosensory event-related potentials].

We studied the topography of somatosensory event-related potentials (SERP) in two different attentive conditions: passive and active. Seventeen healthy right-handed young men, aged 19 to 28 years old (average age; 22.9 years), were requested to perform the following four paradigms in turn. In the passive attentive paradigm, participants were given no specific task when 0.3 Hz electrical stimuli were at random delivered to the right median nerve. In the active attentive paradigm, subjects were required to direct their attention to the regular 0.3 Hz stimuli with all their might. In the control paradigm. 2.0 Hz stimuli were delivered as they listened to their favorite music. Finally, in the oddball paradigm, subjects were instructed to push a button whenever they detected rare stimuli. SERP was recorded at 13 electrodes Grand average topographic amplitude maps from the individual data of the seventeen subjects were made at the latencies of N 60, P 90, N 130 and P 250 for each of the four paradigms. The topographic maps of P 250, the largest positive peak between 200 and 300 msec after the stimuli, showed a significant difference in the distribution of amplitude in the passive and active attentive paradigms compared to the control paradigm. A statistically significant enhancement was noted at the central region in the passive attention, and at the central and frontal regions in the active attention. These results suggest that P 250 consists of two attentive components distinct from selective or discriminative attention. The enhanced positivity at the frontal region during active attention may be associated with expecting the next stimulus and maintaining awareness.

[Electrophysiologic evaluation of passive and active attentions--II. Developmental changes of somatosensory event-related potentials in different attentive paradigms].

By somatosensory event-related potentials (SERP) we have previously demonstrated in adults that an enhanced positivity of P 250 is statistically significant at the frontal region during the active attentive state. We have also evaluated developmental changes of P 250 during different attentive states: passive and active. In this study, 30 healthy children (5-16 years of age) and six healthy adults (23-41 years) were required to perform the following four paradigms: passive attentive, active attentive, control, and oddball. SERP were recorded at Fz, Cz and Pz. In the passive attentive paradigm, P250 amplitude at Fz, Cz and Pz remained constant irrespective of age. With regard to the topography of the amplitude, however, P 250 was distributed dominantly at Pz in Group 1 (5-6 years of age) and Group 2 (7-11 years), contrary to the dominance at Cz in both Group 3 (12-16 years) and adults. In the active attentive paradigm, on the other hand, the P 250 amplitude at Fz reached its minimum at about 10 years and then increased until the adulthood. With respect to the topography of the amplitude, P 250 was distributed dominantly at Pz in Groups 1 and 2, at Cz in Group 3, and at Fz and Cz in adults. These results suggest that the topographic changes in the active attentive paradigm are dependent upon the developing abilities to expect the next stimulus and to maintain awareness.

[Efficacy and side effects of lidocaine by intravenous drip infusion in children with intractable seizures].

Intravenous drip infusions of lidocaine (IDIL; 1-5 mg/kg/h) were performed in ten patients with intractable seizures. The medication was very effective in five patients, whose seizures disappeared immediately after the treatment of IDIL. In four patients, the medication proved to be effective judging from decreased incidence of seizures. In one patient with intractable seizures, the therapy was not effective. In nine patients with the effective medication, five had generalized seizures and four had partial seizures. Side effects were observed in four patients. Two patients had muscle hypotonia, one had visual and auditory hallucination and another had bradycardia. These symptoms completely disappeared after the ceasing of IDIL. Serum concentrations of lidocaine at the appearance of the side effects ranged from 1.8 to 4.7 micrograms/ml, although the toxicity level is more than 5.0 micrograms/ml for arrhythmic adult patients. These findings suggest that the serum toxic level of lidocaine in children is different from that in adults, and that careful observation and appropriate management for the children with lidocaine therapy should be necessary, even though the serum level of lidocaine ranges within the therapeutic level.

[Cerebral cortical dysplasia associated with epilepsy: MRI and clinical aspects].

Clinical and electroencephalographic (EEG) studies were performed in nine patients with cerebral cortical dysplasia (CD). Interictal single photon emission computed tomography (SPECT) using 99mTc-hexamethyl propylene amine oxime were studied in four patients. A patient with hemimegalencephaly and agyria had poor outcome in both developmental and epileptic aspects. The prognoses of clinical seizures were generally related to the severity, location and size of CD. The size of the lesion was not always correlated with the clinical seizure outcome. Four patients had focal pachygyria. Clinical pictures were diverse in these patients. One patient underwent callosotomy for the control of intractable seizures. The others had no clinical seizures despite of the appearance of paradoxical discharges in the area of pachygyria. The distribution of CD detected by MRI did not always correlate with that of paradoxical discharges in EEG and/or hypoperfusional areas seen in SPECT. These findings suggest that a detailed neuroimaging study is useful to elucidate the epileptogenesis in patients with CD, and that all the cortical abnormalities in patients with intractable epilepsy are not detected by MRI.

[Death due to cold of a 63-year-old male associated with hepatocellular carcinoma--bibliographic consideration on alcohol metabolism of the patients with liver dysfunction].

In the early morning of late December, a 63-year-old man was found dead in front of his apartment house. At medico-legal autopsy, subcutaneous hemorrhages of the occipital region and linear fractures of the occipital bone was observed, but there was no cerebral contusion leading him to death. Many white tumors, ranging from 0.5 to 2.0 cm in diameter, were observed in the liver. On sections of the liver, hepatic parenchyma was found entirely occupied by the tumors, which were histopathologically diagnosed as moderately- or well-differentiated hepatocellular carcinoma. Alcohol concentrations of the mixed intracardiac blood and the urine were determined to be 1.9 and 3.6 mg/ml, respectively. Through the police investigation, it became clarified that the male had been sleeping in front of his apartment house about at 10:30 p.m. on the day before he was found dead. The cause of his death was, therefore, considered due to cold, and the authors gave a bibliographic consideration on blood and urine alcohol concentrations and alcohol metabolism of a patient with liver dysfunction due to hepatocellular carcinoma.

[A successful treatment with a continuous intravenous lidocaine for a cluster of minor seizures in a patient with Doose syndrome].

We reported a 7-year-old girl with myoclonic-astatic epilepsy of early childhood (Doose syndrome). She had minor seizures (i. e. absence, atonic and myoclonic seizures) refractory to treatment with many kinds of anti-epileptic drugs as well as thyrotropin releasing hormone. Though she had suffered from long-lasting clusters of minor seizures, the treatment with continuous intravenous lidocaine successfully brought a case of prolonged remission of both clinical seizures and EEG abnormalities. It has been reported that lidocaine is effective mainly for partial seizures. The efficacy of lidocaine for generalize seizures, however, has been reported only in a few papers. We considered that the treatment with continuous intravenous lidocaine is indicated in patients with Doose syndrome presenting with a cluster of refractory minor seizures.