Thermogenesis induced by amino acid administration prevents intraoperative hypothermia and reduces postoperative infectious complications after thoracoscopic esophagectomy.

Minimally invasive thoracoscopic esophagectomy has potential advantages in minimizing the impairment of respiratory function and reducing surgical stress. However, thoracoscopic esophagectomy occasionally results in anesthesia-induced hypothermia, particularly in cases involving artificial pneumothorax with CO2. Thermogenesis induced by amino acid administration has been reported during anesthesia. Here, we tested the efficacy of amino acid treatment for the prevention of hypothermia, and we investigated the potential of this treatment to reduce postoperative infectious complications after thoracoscopic esophagectomy. We conducted a randomized trial in patients with esophageal cancer who underwent thoracoscopic esophagectomy in the prone position in two groups and analyzed the incidences of hypothermia and surgical complications. One-hundred and thirty patients were randomized. Administration of amino acids resulted in a significant increase in core body temperature. In the saline (n = 60) and amino acid (n = 70) administration groups, 30% and 14.2% of patients, respectively, experienced infectious surgical complications (P = 0.029), and 21.6% and 22.8% of patients, respectively, experienced noninfectious surgical complications (P = 0.86). Univariate analysis revealed that blood loss and amino acid administration were significant factors for infectious surgical complications. Multivariate analysis revealed that amino acid administration was an independent factor reducing infectious surgical complications (P = 0.025, 95% confidence interval: 0.105-0.864). Administration of amino acids prevents hypothermia and reduces postoperative infectious complications after thoracoscopic esophagectomy.

Contingent negative variation in children with orthostatic dysregulation.

BACKGROUND: Children with orthostatic dysregulation (OD) appear to have hypodynamia, as well as the symptoms described in the OD criteira. Hypodynamia, which is greatly influenced by motivation, volition and concentration, is unexceptionally recognized in their everyday life. It has been suggested that the symptoms and hypodynamia aggravate considerably the quality of life (QOL) of children with OD. The purpose of this study was to distinguish the characteristics of contingent negative variation (CNV) and post imperative negative variation, which may reflect the level of attention and motivation in children with OD. METHODS: Twelve patients with OD aged 10-15 years and 23 age-matched healthy children were included. The CNV was recorded from Fz, Cz and Pz linked to earlobes during 30 trials consisting of a warning stimulus and an imperative stimulus with an interstimulus interval (ISI) of 2 s and an intertrial interval (ITI) of 10 s. The imperative stimulus of each trial required a button to be pressed. RESULTS: The untreated children with OD did not have a significantly smaller CNV amplitude than healthy children. Children with OD treated with midodrine and autonomic training had a significantly larger CNV amplitude than the untreated children, in the area of early, late and total CNV at the three sites. CONCLUSION: The present study confirms that children with OD have diminished motivation and deterioration of concentration, which cause hypodynamia in everyday life. Treatment for OD improves the symptoms, diminished motivation and deterioration of concentration, consequently restoring dynamia. Treatment for OD should be recommended to ameliorate QOL of children with OD.

Excessive release of [3H] noradrenaline by veratridine and ischemia in spinal cord.

In this study, the properties of ischemic condition-induced and veratridine-evoked [3H]noradrenaline ([3H]NA) release from rat spinal cord slices were compared. It was expected that ischemia mimicked by oxygen and glucose deprivation results in the impairment of Na+/K+ -ATPase with a consequent elevation of the intracellular Na+ -level which reverses the NA carrier and promotes excessive NA release, and veratridine, by the activation of Na+ channels, releases NA both carrier-mediated and Ca2+ -dependent, i.e. vesicular manner. In our experiments, veratridine (1-100 microM) dose-dependently increased the resting [3H]NA release, and its effect was only partially blocked by low temperature or the lack of external calcium, whereas the sodium channel inhibitor tetrodotoxin (TTX, 1 microM) completely prevented it, indicating that veratridine induces NA release via axonal depolarization and reversing the transporters by eliciting Na+ -influx. In contrast to TTX, the local anesthetic lidocaine (100 microM) only partially blocked the veratridine-induced [3H]NA release due to its inhibitory action on K+ channels. The ischemia-induced [3H]NA release was abolished at 12 degrees C, a temperature known to block only the transporter-mediated release of transmitters. However, lidocaine was also partially effective to reverse the action of ischemia on the NA release, indicating that lidocaine is not a useful compound in the treatment of spinal cord-injured patients against the excessive excytotoxic NA release.

Aqueous dispersion behavior of drug particles by addition of surfactant and polymer.

The effect of surfactant and polymer on dispersion stability of aqueous suspensions of 5-(3-ethoxy-4-pentyloxyphenyl)-2,4-thiazolidinedione (CT112) was investigated by measuring the adsorbed amount of surfactant and polymer, zeta potential, particle size, and sedimentation rate of CT112. The addition of celluloses rather than sodium dodecyl sulfate (SDS) provided a high stable suspension of CT112. In addition, mixed systems of celluloses and SDS enhanced CT112 dispersion more effectively. The mechanism of dispersion stability of CT112 by addition of SDS and celluloses is discussed.

Complete paternal uniparental isodisomy for chromosome 1 revealed by mutation analyses of the TRKA (NTRK1) gene encoding a receptor tyrosine kinase for nerve growth factor in a patient with congenital insensitivity to pain with anhidrosis.

Uniparental disomy (UPD) is defined as the presence of a chromosome pair that derives from only one parent in a diploid individual. The human TRKA gene on chromosome 1q21-q22 encodes a receptor tyrosine kinase for nerve growth factor and is responsible for an autosomal recessive genetic disorder: congenital insensitivity to pain with anhidrosis (CIPA). We report here the second case of paternal UPD for chromosome 1 in a male patient with CIPA who developed normally at term and did not show overt dysmorphisms or malformations. He had only the usual features of CIPA with a homozygous mutation at the TRKA locus and a normal karyotype with no visible deletions or evidence of monosomy 1. Haplotype analysis of the TRKA locus and allelotype analyses of whole chromosome 1 revealed that the chromosome pair was exclusively derived from his father. Non-maternity was excluded by analyses of autosomes other than chromosome 1. Thus, we have identified a complete paternal isodisomy for chromosome 1 as the cause of reduction to homozygosity of the TRKA gene mutation, leading to CIPA. Our findings further support the idea that there are no paternally imprinted genes on chromosome 1 with a major effect on phenotype. UPD must be considered as a rare but possible cause of autosomal recessive disorders when conducting genetic testing.

Kinetics of Simultaneous Adsorption of Poly(vinylpyrrolidone) and Sodium Dodecyl Sulfate on Alumina Particles.

The adsorption kinetics of poly(vinylpyrrolidone) (PVP) and sodium dodecyl sulfate (SDS) on alumina particles at pH 3.5 has been studied by measuring the amount of PVP and SDS adsorbed and the dispersion stability of solid suspensions with time. Although PVP alone hardly adsorbs on alumina particles, the adsorption of PVP is enhanced by coadsorption of SDS. In the simultaneous adsorption of PVP-SDS at two initial concentrations of SDS which correspond to the formation of a monolayer and a bilayer of SDS, respectively, the adsorption behavior of PVP with time is significantly affected by the initial SDS concentration. In addition, the dispersion stability of alumina suspensions also changes due to the adsorption of SDS-PVP with time. The mechanism of adsorption kinetics of PVP and SDS on alumina particles is discussed. Copyright 2000 Academic Press.

Infant case with a malignant form of Brugada syndrome.

We report a 6-month-old Japanese infant with a malignant form of Brugada syndrome, who had frequent episodes of ventricular fibrillation (VF) and nonsustained polymorphic ventricular tachycardia (VT). To the best of our knowledge, this infant is the youngest patient reported to have Brugada syndrome. Continuous infusion of a beta-adrenergic agonist and intravenous injection of a parasympathetic antagonist suppressed the electrical storm of polymorphic VT and VF. Combined oral administration of a beta1-adrenergic agonist, a parasympathetic antagonist, and quinidine has successfully suppressed recurrences of VT or VF for 6 months, and the combination may have the potential to decrease the incidence of VT or VF as an adjunctive therapy with prophylactic placement of an implantable cardioverter defibrillator.

The specific expression of three novel splice variant forms of human metalloprotease-like disintegrin-like cysteine-rich protein 2 gene inBrain tissues and gliomas.

We have previously identified 67 exons on a yeast artificial chromosome contig spanning 1.5 Mb around the multidrug resistance 1 gene region of human chromosome 7q21.1. In this study, we identified three novel cytoplasmic variants (MDC2-gamma, MDC2-delta, and MDC2-epsilon) of the human metalloprotease-like disintegrin-like cysteine-rich protein 2 (MDC2) among these exons by screening a human brain cDNA library and also by using a reverse transcription polymerase chain reaction. Genomic sequence analysis strongly supported the idea that the variations in the cytoplasmic domain were generated by alternative splicing. The expression of MDC2 variant forms in human brain tissue and gliomas was examined by reverse transcription polymerase chain reaction and RNase protection assay. MDC2-epsilon was expressed only in the cortical and hippocampal regions in human brain, but not in gliomas. In contrast, MDC2-gamma was a major form expressed in human gliomas. Specific expression of these cytoplasmic variants of MDC2 in human brain and its malignancies is discussed.

[A new sedation technique with propofol during spinal anesthesia].

We compared our new sedation technique with propofol during spinal anesthesia (Group B, n = 50) with a previously described method by Mackenzie et al. (Group A, n = 20). In Group A, propofol was started at a rate of 6 mg.kg-1.h-1 for 10 minutes, followed by continuous infusion at a rate of 4 mg.kg-1.h-1 till the end of surgery. In Group B, propofol 0.4 mg.kg-1 was administered by a bolus injection at the beginning. One-hundred and fifty minutes after the first injection, propofol 0.2 mg.kg-1 was added. The third dose of 0.1 mg.kg-1 of propofol was given 150 seconds after the second dose, followed by continuous infusion at a rate of 4 mg.kg-1.h-1 till the end of surgery. When adequate sedation was not obtained in Group B, propofol 0.1 mg.kg-1 was added by bolus fashion occasionally. In Group A, it took 9 min. 29 sec. to complete adequate sedation assessed by Mackenzie and Grant's sedation score. On the other hand, in Group B, it was 7 min. 27 sec. (P < 0.05 compared with Group A). There was neither excitation nor movement during sedation in Group B, while 5 patients experienced such events in Group A. The blood concentrations of propofol in Group B was 0.946 +/- 0.076 microgram.ml-1 and 0.693 +/- 0.136 microgram.ml-1 at 5 minutes and 10 minutes after the beginning of propofol, respectively. These values were significantly lower than those reported by Kugimiya. Our newly developed method for sedation with propofol during spinal anesthesia would be safer and more effective than that previously described by Mackenzie et al.

Preparation of Hydrophobically Modified Poly(amidoamine) Dendrimer-Encapsulated Gold Nanoparticles in Organic Solvents.

HAuCl(4) in aqueous solution was extracted to toluene or chloroform using a hydrophobically modified poly(amidoamine) dendrimer. Then, by reduction of Au(3+) ions with dimethylamineborane, gold nanoparticles in the size range of 2-4 nm were obtained in toluene or chloroform. It is suggested that gold nanoparticles are encapsulated by the dendrimer. Copyright 2000 Academic Press.

Influence of emission from rice straw burning on bronchial asthma in children.

BACKGROUND: Emission from rice straw burning (ERSB) is observed everywhere after harvest of rice in Niigata Prefecture every year. Pediatricians and many guardians in this district have had the impression that ERSB may induce asthma attack. Recent studies have suggested that particulate air pollution plays a role in the exacerbation of asthma. The authors investigated relationship of ERSB to asthma attack in children. METHODS: A questionnaire on rice straw burning (RSB) was circulated to guardians and pediatric institutions. Change in the monthly number of children with asthma attack (CAA) for 5 years from January 1994 to December 1998 was investigated. In addition, change in the number of CAA from the meteorologic conditions and RSB was investigated from the fourth week of August to the third week of September in 1996, 1997 and 1998. Challenge test exposure to ERSB was tried on a volunteer adult with chronic asthma. The situation of air pollution was examined by measuring suspended particulate matter (PM10). The relationship between PM10 and the number of CAA was studied. RESULTS: A majority of the guardians had the impression that ERSB induces asthma attack. Pediatricians replied similarly to the questionnaire. The number of CAA visiting our emergency room and admitted to our ward increased in the season of RSB. The PM10 had a significant correlation with the number of CAA. It was suggested that the increase in CAA may be not due to the meteorologic conditions, but to the influence of ERSB. CONCLUSION: The ERSB has made an issue of air pollution. Furthermore, the possibility that ERSB induces or exacerbates asthma attack has become clear in the present study. Therefore, it is recommended that RSB should be abolished for the health of inhabitants, especially children with asthma.

Reexamination of 2-Naphthol Adsolubilization on Alumina with Sodium Dodecyl Sulfate Adsorption.

Adsolubilization behavior of 2-naphthol on alumina with adsorption of sodium dodecyl sulfate (SDS) at pH 3.5 in the presence of 10 mmol dm(-3) NaCl was reexamined. The adsolubilized amount of 2-naphthol increased sharply and reached a maximum, then decreased with SDS concentration. The decrement of the adsolubilized amount began below the critical micelle concentration of SDS. From the dispersion state of the alumina suspension and the SDS adsorption isotherm, it is demonstrated that the decrement of adsolubilization of 2-naphthol is not due to the partition of 2-naphthol between the SDS adsorbed layer and SDS micelles, but is due to the difference of SDS adsorption states such as monolayers and admicelles. Copyright 2000 Academic Press.

IL-12 synergizes with IL-18 or IL-1beta for IFN-gamma production from human T cells.

IL-18 is a proinflammatory cytokine that plays an important role in NK cell activation and T(h)1 response. IL-18 has a structural homology to IL-1, particularly IL-1beta. IL-18R, composed of IL-1R-related protein (IL-18Ralpha) and IL-1R accessory protein-like (IL-18Rbeta), belongs to the IL-1R family. Furthermore, IL-18R at least partly shares the signal transducing system with IL-1R. Thus, the IL-18-IL-18R system has a striking similarity to the IL-1-IL-1R system. For this reason, we regarded it important to investigate whether, like IL-18, IL-1beta synergizes with IL-12 in inducing IFN-gamma production from human T cells and plays an important role in the T(h)1 response. Here we show that IL-12 and IL-1beta synergistically induce T cells to proliferate and produce IFN-gamma without their TCR engagement. IL-12 stimulation induced an increase in the proportion of T cells positive for IL-18R. Then, IL-12-stimulated T cells responded to IL-18 or IL-1beta by their proliferation and IFN-gamma production, although levels of IL-1beta-induced responses were lower. CD4(+)CD45RA(+) T cells, although they constitutively expressed IL-18Rbeta mRNA, did not express IL-18Ralpha mRNA. Phytohemagglutinin (PHA) stimulation alone induced IL-18Ralpha mRNA without affecting the expression of IL-18Rbeta mRNA. T(h)1-inducing conditions (PHA, IL-12 and anti-IL-4) further increased this expression. We also show that T(h)1 cells but not T(h)2 cells have increased expression of IL-18R and IL-1R, and produce IFN-gamma in response to IL-18 and/or IL-1beta.

Physicochemical Properties of 2-Vinylpyridine Telomers Possessing Multihydrocarbon Chains in Aqueous Solution and at the Silica/Aqueous Solution Interface.

Physicochemical properties of multialkylated surfactants of partially quaternized 2-vinylpyridine telomers having multihydrocarbon side chains (nRm-2VPQ: n, number of chains; m, alkyl chain length) in aqueous solutions were investigated. The critical micelle concentration (cmc) and surface tension at the cmc were 13 µmol dm(-3) and 52 mNm(-1) for 2.1R(8)-2VPQ, 7.1 µmol dm(-3) and 37 mNm(-1) for 2.5R(12)-2VPQ, and 4.7 µmol dm(-3) and 40.0 mNm(-1) for 3.4R(12)-2VPQ, respectively. The aggregation numbers at the cmc determined by the light scattering method were 4 +/- 1 for 2.1R(8)-2VPQ, 45 +/- 10 for 2.5R(12)-2VPQ, and 11 +/- 1 for 3.4R(12)-2VPQ. Thus, the number of chains and the alkyl chain length of the telomers affected the micellar properties in aqueous solutions. At the interface of the silica/aqueous solution, the adsorbed amounts of the telomers increased sharply at their low concentrations and reached a plateau by forming a monolayer and a subsequent bilayer. Silica suspensions also showed a dispersion-flocculation-redispersion sequence with the telomer concentration, where the maximum sedimentation rate was influenced by the number of chains and the alkyl chain length of the telomers. Copyright 1999 Academic Press.

[Stimulation and inhibition mechanisms in peripheral nerve regeneration].

To better analyse the early growth of peripheral nerve regeneration, we recently developed a film model. Following transection of a peripheral nerve, e.g. the common peroneal nerve in mice, both proximal and distal stumps of the transected nerve are sandwiched between two sheets of film, and kept in vivo for various timed intervals after axotomy. The regenerating neurites sprout not only from the nodes of Ranvier close to the transected nerve end but also from the terminal bulbs which are formed at the transected nerve end. All of the regenerating neurites consist of naked axons for at least 2 days after axotomy, and elongate on the film with a growth rate of 77 microns/day. On migrating from a parent nerve to the regenerating axons, Schwann cells promote the axons to grow with a 4 times higher speed. Thereafter, a distal nerve stump of the transected nerve release some stimulating factors toward the regenerating nerves, and the axonal growth rate is increased by approximately 1.5 fold. Some inhibitory factors, one of which is myelin-associated glycoprotein, are at the same time released from the distal nerve segment for a week from the 7th post-operative day, and keep new axons from sprouting and inhibit outgrowth of young naked axons in order to optimum regeneration and maturation of outgrowing pioneer axons. It means a so-called pruning phenomenon.

Simultaneous exposure to interleukin-18 and interleukin-10 in vitro synergistically augments murine spleen natural killer cell activity.

Interleukin-18 (IL-18) enhances interferon gamma (IFNgamma) production and natural killer (NK) cell activity, and elicits protective antitumor effects in vivo. IL-18 and IL-12 synergistically augment IFNgamma production reportedly because IL-12 enhances IL-18 receptor (IL-18R) expression. We now show that IL-18 also synergizes with IL-10 to augment murine splenic NK activity against Yac-1 cells in a standard 4-h chromium-release assay, but IFNgamma production is only slightly enhanced. This pattern of NK activity was also observed with severe combined immunodeficient (SCID) mouse spleen cells indicating that the cytokines were not acting on T or B cells. The cytokines had no priming activity on the spleen cells and, when cells were left unstimulated for 24 h in culture, little NK activity was induced when IL-18 was added for the next 24 h. The reverse transcriptase/polymerase chain reaction revealed that IL-18 receptor (IL-18R) mRNA was expressed early during in vitro spleen cell culture but none was expressed after culture for 24 h regardless of the stimulus. Binding of 125I-labeled IL-18 revealed that exposure to IL-10 only slightly increased IL-18R expression. Expression of perforin mRNA was constitutive and was unaffected by the cytokines; however, Fas ligand (FasL) mRNA expression was strong in cultures with IL-18 alone or combined with IL-10. When Fas-expressing cells and their parental cells were used as targets, weak Fas-mediated cytolytic activity was observed after exposure to IL-18, and this was further enhanced by combination with IL-10. Finally, the augmentation of NK activity was abrogated by the inhibitor concanamycin A, indicating that the enhanced NK activity is perforin-dependent.

Branched-chain amino acid-induced hippocampal norepinephrine release is antagonized by picrotoxin: evidence for a central mode of action.

Previous studies indicated that administration of a 1:1:1 mixture of the branched-chain amino acids leucine, isoleucine, and valine (BCAA) decreased the response to pain. The present study investigates the effects of BCAA on release of norepinephrine (NE) from isolated hippocampal brain slices. BCAA evoked 3H-NE release in a concentration-dependent manner. This effect was antagonized by the gamma aminobutyric acid (GABA) receptor antagonist picrotoxin, again in a concentration-dependent manner, suggesting that the effect may be mediated via a GABA receptor. Given the role of NE and of GABA receptors in the central response to pain, it is possible that the BCAA may exert their antinociceptive properties through activation of GABA receptors.

Contingent negative variation in children with anorexia nervosa.

BACKGROUND: Central catecholamines, particularly dopaminergic and noradrenergic systems, have affected the appetitive behavior in patients with anorexia nervosa (AN). The purpose of this study is to distinguish the characteristics of contingent negative variation (CNV) and postimperative negative variation (PINV), which may reflect the level of catecholamine in children with AN. METHODS: Eight children with AN aged 10 to 15 years and 23 age-matched healthy children were recruited. Contingent negative variation was recorded from the frontal midline (Fz), central midline (Cz) and parietal midline (Pz) referenced to linked earlobes during 30 trials consisting of a warning stimulus and an imperative stimulus with an interstimulus interval of 2 s and an intertrial interval of 10 s. The imperative stimulus of each trial required a button press. RESULTS: Children with AN had a diminished amplitude of the CNV. They had a significantly more attenuated early CNV and late CNV amplitude at Cz than normal children. No significant differences were observed between AN children and normal children in the amplitude of PINV at all three electrode sites. No difference could be found between the two groups in the frequencies of normal and abnormal duration of PINV. CONCLUSION: These findings suggest that early CNV may be diminished by norepinephrine deficiency and late CNV may be attenuated by dopaminergic deficiency in children with AN. Reduced CNV may represent impaired cognitive processes which reflect impaired appetitive behavior in AN children.