Application of ligating loops to control bleeding during endoscopic surgery for a highly vascular hypopharyngeal tumour.

Endoscopic treatment of hypervascular lesions of the hypopharynx is challenging because of difficulty in controlling bleeding during surgery. We report a highly vascular hypopharyngeal solitary fibrous tumour treated by endoscopic laser surgery combined with ligating loops. Application of dual ligating loops provided easy and secure haemostasis of the feeding artery before resection. Since the endoscopic approach is less invasive than the external approach, we confirm that it is worthwhile to attempt an endoscopic approach using ligating loops before resorting to the external approach in the treatment of hypervascular hypopharyngeal lesions.

Multiple laryngeal foreign bodies composed of dried fish vertebral bones: a case report.

We present a rare case of tracheostomy for removal of laryngeal foreign bodies consisting of three connected fish vertebral bones in a 15-month-old girl. Recent endoscopic techniques have made it possible to extract nearly all tracheobronchial foreign bodies with rigid bronchoscopes. However, the three connected foreign bodies in this report could not be extracted entirely by single endoscopy because the glottis as an exit was narrow due to severe oedema. Accordingly, tracheostomy was required to assist ventilation, prevent prolonged post-operative endotracheal intubation, remove the secondary tracheal foreign bodies and to provide a conduit for the introduction of a bronchoscope. This suggests that tracheostomy should be considered to avoid the potential dangers of severe laryngeal oedema and to secure the route for removal of foreign bodies from the trachea when treating patients with multiple laryngeal foreign bodies and laryngeal oedema.

Preliminary study on the effects of bar placement on the thorax after the nuss procedure for pectus excavatum using bone scintigraphy.

AIM: Bone scintigraphy was performed to elucidate the effects of the Nuss procedure for pectus excavatum on the bony thorax. METHODS: Eight boys and 6 girls (5 - 24 years of age) underwent bone scintigraphy, using (99m)Tc-HMDP. Eleven patients were studied 5 to 21 days after the Nuss procedure; 6 were studied 20 to 24 months after the operation before bar removal. Three of 14 were studied twice after the Nuss procedure and before bar removal. RESULTS: In the early postoperative phase, RI accumulation was found at the sternum and ribs in only 1 of 6 patients under 9 years of age, whereas in all 5 older patients, RI had accumulated at the sternum. Scintigrams before bar removal revealed, regardless of age, hot spots at the lateral ribs in contact with the bar and at the costochondral junctions where the bar passed through the intercostal spaces. Furthermore, chest roentgenograms showed the deformed lateral ribs in contact with the bar. CONCLUSIONS: The Nuss procedure creates minute fractures at the sternum and the ribs, especially in older patients. The bar deforms the ribs and restrains the growth of the thorax. Furthermore, it constantly rubs against the ribs and can therefore cause late complications. Bone scintigraphy may determine the appropriate timing for bar removal.

Indications for surgical treatment of funnel chest by chest radiograph.

Forty-seven children with funnel chest (FC) who underwent sternal elevation and 210 normal children were examined to determine the indications for surgical treatment using the vertebral index (VI) and frontosagittal index (FSI). In normal children VI gradually increased and FSI gradually decreased with age. Both indices changed significantly at 3 years of age. Although the VI of FC patients decreased significantly from 33.8 +/- 7.6 (n=40) to 24.4 +/- 3.9 (n=38) postoperatively (P < 0.0001), it was significantly larger than that of normal children over 3 years of age (20.2 +/- 2.2, n=150) (P < 0.0001), and although the FSI of FC patients increased significantly from 22.0 +/- 7.0 (n=40) to 34.5 +/- 6.5 (n=38) postoperatively (P < 0.0001), it was significantly smaller than that of normal children over 3 years of age (41.1 +/- 4.0, n=150) (P < 0.0001). Since many patients had a thin and flat chest despite excellent correction, their postoperative indices were not normal. There was a correlation between VI and FSI in normal children and a high degree of correlation between VI and FSI both before and after operation in FC patients. We conclude that a VI of more than 27 and/or a FSI of less than 29 are indications for surgical treatment based on the mean VI + 3SD and FSI - 3SD of normal children over 3 years of age. These values are almost equal to the mean VI - SD and FSI + SD of patients with physical, cosmetic, and/or psychological disturbances. However, it is not necessary to measure both indices simultaneously. Postoperative VI and FSI did not always reflect the degree of chest-wall depression in FC patients because of their flat chests.

An absolute requirement for STAT4 and a role for IFN-gamma as an amplifying factor in IL-12 induction of the functional IL-18 receptor complex.

IL-12 and IL-18 are both proinflammatory cytokines that contribute to promoting Th1 development and IFN-gamma expression. However, neither IL-12R nor IL-18R is expressed as a functional complex on most resting T cells. This study investigated the molecular mechanisms underlying the induction of an IL-18R complex in T cells. Resting T cells expressed IL-18Ralpha chains but did not exhibit IL-18 binding sites as detected by incubation with rIL-18 followed by anti-IL-18 Ab, suggesting a lack of IL-18Rbeta expression in resting T cells. Although they also failed to express IL-12R, stimulation with anti-CD3 plus anti-CD28 generated IL-12R. Exposure of these cells to IL-12 led not only to up-regulation of IL-18Ralpha expression but also to induction of IL-18R binding sites on both CD4(+) and CD8(+) T cells concomitant with IL-18Rbeta mRNA expression. The IL-18 binding site represented a functional IL-18R complex capable of exhibiting IL-18 responsiveness. IL-12 induction of an IL-18R complex and IL-18Rbeta mRNA expression was not observed in STAT4-deficient (STAT4(-/-)) T cells and was substantially decreased in IFN-gamma(-/-) T cells. However, the failure of STAT4(-/-) T cells to induce an IL-18R complex was not corrected by IFN-gamma. These results indicate that STAT4 and IFN-gamma play an indispensable role and a role as an amplifying factor, respectively, in IL-12 induction of the functional IL-18R complex.

Molecular diversity in zebrafish NCAM family: three members with different VASE usage and distinct localization.

NCAM in vertebrates and its related molecules, apCAM in Aplysia, fasciclin II in Drosophila, and OCAM in mammals, play key roles in various aspects of brain development and functions. In this study, we have identified and characterized three members of the NCAM gene family in zebrafish, designated as zNCAM, zOCAM, and zPCAM. Three molecules exhibit similar domain organization: an amino-terminal signal peptide, five immunoglobulin-like domains, two fibronectin type III-like domains, a transmembrane segment, and a carboxy-terminal cytoplasmic region. A novel molecule zPCAM is most closely related to zNCAM with 66% amino acid identity. Diversity in the extracellular region of zPCAM is generated by insertion of two different types of variable alternatively spliced exons. In situ hybridization analysis revealed that three molecules were specifically expressed by the central and peripheral nervous systems from early developmental stages in region-specific and cell-type-specific manners. For example, zPCAM showed a neuromere-specific segmental expression pattern, while zOCAM first appeared in specific clusters of secondary neurons in the forebrain. These results suggest that each member of the NCAM gene family plays distinct roles in the formation and maintenance of functional neuronal networks in the zebrafish nervous system.

Left vocal cord paralysis associated with long-standing patent ductus arteriosus.

SUMMARY: Left vocal cord paralysis in association with patent ductus arteriosus is unusual. We report a patient with long-standing patent ductus arteriosus (PDA) in whom CT studies obtained before and after paralysis developed showed an interval increase in size of the pulmonary trunk. The pathogenesis of left vocal cord paralysis in association with long-standing PDA is discussed.

Neurofibroma of the larynx in neurofibromatosis: preoperative computed tomography and magnetic resonance imaging.

Neurofibromas of the larynx are extremely rare. They occur in association with neurofibromatosis less frequently than solitary neurofibromas. However, most laryngeal tumors in neurofibromatosis are neurofibromas. This disorder has 2 histological subtypes, which require different surgical approaches because of their biological differences. Few cross-sectional imaging studies have been performed in neurofibroma of the larynx. We describe a 44-year-old man with neurofibromatosis and nonplexiform neurofibroma of the larynx and discuss the role of preoperative computed tomography and magnetic resonance imaging in this case. The tumor was removed completely using an endolaryngeal approach without an external incision. It was possible to distinguish subtypes preoperatively on cross-sectional imaging. Magnetic resonance imaging provided more sensitive information in the diagnosis of this tumor than computed tomography. Preoperative cross-sectional imaging should be performed to help the surgeon diagnose and choose an appropriate surgical approach for this disorder.

Differential effects of N-acetyl-l-cysteine on IL-2- vs IL-12-driven proliferation of a T cell clone: implications for distinct signalling pathways.

Using a T cell clone (2D6) capable of responding to IL-2 and IL-12, we compared the effects of NAC on IL-2 and IL-12-driven T cell proliferation. Addition of N-acetylcysteine (NAC) to 2D6 cultures did not affect IL-2 stimulated proliferation, but strikingly inhibited IL-12 stimulated proliferation. These differential NAC effects did not correlate with the patterns of the mitogen-activated protein kinase (MAPK) activation following cytokine stimulation and its regulation by NAC. Although a p38 MAPK inhibitor downregulated both IL-2- and IL-12-induced proliferation, this effect was seen at drug concentrations one order higher than those reportedly used to specifically inhibit p38 MAPK. The results suggest the existence of distinct signalling pathways and a common, indispensable signalling molecule in IL-2- and IL-12 driven T cell proliferation.

Tumor vaccination that enhances antitumor T-cell responses does not inhibit the growth of established tumors even in combination with interleukin-12 treatment: the importance of inducing intratumoral T-cell migration.

Interleukin-12 (IL-12) treatment is effective in the CSA1M but not in the Meth A and CSA1M-variant tumor models. The authors investigated the cause by which IL-12 treatment fails to induce tumor regression in these two tumor models. T cells from CSA1M-bearing mice have high levels of IL-12 responsiveness, whereas cells from Meth A-bearing mice display marginal levels of responsiveness. Because IL-12 responsiveness in T cells is induced after T-cell receptor stimulation, the lack of IL-12 responsiveness suggests that T cells in Meth A-bearing mice are not sensitized to Meth A tumor antigen. Immunization of normal mice with attenuated Meth A tumor cells resulted in a protective immunity, as shown by the rejection of challenged viable Meth A cells. Such an immunization, when performed in Meth A-bearing mice, induced potent IL-12 responsiveness in T cells. Nevertheless, IL-12 treatment in these mice did not inhibit tumor growth. In another IL-12-incurable (CSA1M-variant) model, IL-12 responsiveness was observed before tumor cell immunization. However, IL-12 treatment was ineffective regardless of whether tumor cell immunization was performed. In these two models, the failure of IL-12 treatment to induce tumor regression was associated with the lack of T-cell migration to tumor sites. These results indicate that the sensitization of T cells to tumor antigens and generation of IL-12 responsiveness are insufficient to induce tumor regression when these sensitized T cells are not allowed to migrate to tumor sites.

Sarcoidosis with vocal fold involvement and hypercalcaemia.

Sarcoidosis affects many different organ systems. However, laryngeal involvement is rare and most cases with laryngeal involvement affect the supraglottis, occasionally secondarily extending to the vocal fold. The features of sarcoidosis in the supraglottic region have been described in several reports, but vocal fold involvement has not been presented in detail. We report an unusual case of laryngeal sarcoidosis initially involving the vocal folds in a 66-year-old man, associated with hypercalcaemia. Our report describes characteristics of the involved vocal folds. Hypercalcaemia is one of the characteristics of sarcoidosis. We concluded that laryngeal sarcoidosis should be added to the differential diagnosis of vocal fold lesions, particularly in patients with hypercalcaemia.

Left vocal cord paralysis as a primary manifestation of invasive pulmonary aspergillosis in a nonimmunocompromised host.

We report the first case (to our knowledge) of vocal cord paralysis as a primary manifestation of invasive pulmonary aspergillosis, which occurred in a 69-year-old woman without immunodeficiency. Her chest radiograph showed left upper lobe infiltration with pleural thickening, and a computed tomogram of her chest showed a thick pleural reaction and fibrosis around the arch of the aorta. A transbronchial biopsy specimen revealed Aspergillus infection. The patient was treated with oral itraconazole. However, since vocal cord paralysis persisted, the patient underwent type I thyroplasty to improve vocal function. A review of the literature showed that the incidence of invasive pulmonary aspergillosis has increased, even in nonimmunocompromised subjects, and that the disease has a potential for recurrent laryngeal nerve palsy. Therefore, invasive pulmonary aspergillosis should be considered in patients with vocal cord paralysis.

A genetic approach to visualization of multisynaptic neural pathways using plant lectin transgene.

The wiring patterns among various types of neurons via specific synaptic connections are the basis of functional logic employed by the brain for information processing. This study introduces a powerful method of analyzing the neuronal connectivity patterns by delivering a tracer selectively to specific types of neurons while simultaneously transsynaptically labeling their target neurons. We developed a novel genetic approach introducing cDNA for a plant lectin, wheat germ agglutinin (WGA), as a transgene under the control of specific promoter elements. Using this method, we demonstrate three examples of visualization of specific transsynaptic neural pathways: the mouse cerebellar efferent pathways, the mouse olfactory pathways, and the Drosophila visual pathways. This strategy should greatly facilitate studies on the anatomical and functional organization of the developing and mature nervous system.

Paracoccus denitrificans aromatic amino acid aminotransferase: a model enzyme for the study of dual substrate recognition mechanism.

The gene for aromatic amino acid aminotransferase (ArAT) from Paracoccus denitrificans was cloned, sequenced, and overexpressed in Escherichia coli cells. The sequence differed from that reported previously [Takagi, T., Taniguchi, T., Yamamoto, Y., and Shibatani, T. (1991) Biotechnol. Appl. Biochem. 13, 112-119]. The enzyme (pdArAT) was purified to homogeneity, and characterized. It was similar to aspartate aminotransferase (AspAT) and ArAT of E. coli (ecArAT) in many respects, including gross protein structure and spectroscopic properties. pdArAT showed activities toward both dicarboxylic and aromatic substrates, and analysis of the binding of substrate analogs and quasisubstrates to the enzyme showed that both dicarboxylic and aromatic substrates take a similar orientation in the active site of pdArAT; these properties are essentially identical with those of ecArAT. As in the case of ecArAT, neutral amino acids with larger side chains are better substrates for pdArAT, suggesting that hydrophobic interaction between the substrate and the enzyme is important for the recognition of substrates with neutral side chains. pdArAT catalyzed transamination of phenylalanine and tyrosine far more efficiently (10(2)-fold in terms of kcat/Km) than those of straight-chain aliphatic amino acids with similar side-chain surface area, whereas ecArAT did not show significant preference for aromatic amino acids over aliphatic amino acids. This shows that the substrate-side-chain-binding pocket of pdArAT, as compared with the pocket of ecArAT, is well suited in shape for interaction with the phenyl and hydroxyphenyl rings of substrates. Thus, pdArAT is an ideal enzyme among ArATs for the study of the high-specificity recognition of two different kinds of substrates, the one having a carboxylic side chain and the other having an aromatic side chain.

Intraosseous hemangioma of the vomer: a case report.

We describe an unusual case of intraosseous hemangioma of the vomer. The lesion had a characteristic radiographic appearance, especially on the computed tomographic scan. The two most interesting points in this case were the rarity as a site for the occurrence of hemangioma and the successful extirpation of the tumor via the Le Fort 1 osteotomy approach without embolization of the feeding vessels. The benefits of this approach included the wide surgical field afforded deep in the midface region, which was important for controlling bleeding, as well as the complete extirpation of the tumor.

Leiomyoblastoma causing acute gastric outlet obstruction in an infant.

A 1-year-old boy had acute gastric outlet obstruction, the cause of which was a prepyloric submucosal mass. The mass and the ulcerated overlying mucosa were excised. The histological diagnosis was leiomyoblastoma with parenchymatous hemorrhage. Apparently, he is the youngest patient reported to have this disease.

Esophagitis in infants with hypertrophic pyloric stenosis: a source of hematemesis.

This study was undertaken to clarify the source of blood in the vomitus of patients with hypertrophic pyloric stenosis (HPS). Twenty-one infants with HPS were examined. Hematemesis was noted in 14 infants. Esophagogastric endoscopy showed a 100% incidence of esophagitis and in one patient gastric erosion was also observed. Histological study of the esophageal mucosa showed evidence of esophagitis in 18 patients (85.7%). Preoperative pH monitoring showed gastroesophageal reflux (GER) in all infants. Excessive acid exposure (> or = 7%) was significantly correlated with the grade of esophagitis and the incidence of hematemesis, whereas acid exposure time was shorter in the cases without histological esophagitis. These results suggested that the source of bleeding in HPS is the esophageal mucosa affected by esophagitis secondary to excessive acid reflux. Although there is obvious massive gastroesophageal reflux in HPS, it is too difficult to evaluate the lower esophageal sphincter function in HPS.

Manometric diagnosis of Hirschsprung's disease in the neonatal period.

A newly designed semiconductor manometer was assembled for anorectal manometry in the neonatal period. Sixty apparently healthy neonates and 17 patients who presented gastrointestinal obstructive symptoms were examined by the eighth day of life. All 60 apparently healthy neonates showed a normal fluctuating wave and rectoanal reflex. Prematurity and postnatal age do not influence the normal rectoanal reflex. Among 17 patients, 5 were diagnosed as having Hirschsprung's disease based on absence of the reflex. There were no false negative or false positive results among these cases. It appears that anorectal manometry could be a reliable diagnostic test of Hirschsprung's disease even in the neonatal period.

Neonatal gastric perforations; a diagnostic clue in pre-perforative phase.

This paper is a retrospective analysis of the pre-perforative clinical picture in twenty-seven neonates with gastric perforations. In fifteen there was a remarkably consistent progressive pattern in the preperforative clinical course. We separated the clinical course of the disease into three distinct stages in relation to pathological changes in the gastric wall i.e. gastric ischemia and dysfunction, transmural peritonitis and paralytic ileus, and actual perforation. Emphasis was placed on the existance of a clinically detectable pre-perforative phase which, if interpreted correctly, should lead to earlier diagnosis and consequently more satisfactory therapeutic results.