Antroduodenal motor function and gastro-oesophageal reflux in neurologically impaired children, adolescents and young adults.
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Biomedical subjects
Publications and source records attributed to A Okada.
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Crohn's disease is associated with complications in multiple organs. However, there are very few reported cases of patients with Crohn's disease with muscle symptoms and/or high serum creatine phospho-kinase (CPK) levels. We report here a patient with Crohn's disease who experienced skeletal muscle damage with extremely high serum CPK level during treatment with an elemental diet. The non-parenteral administration of large amounts of carbohydrate and limited glycogen degradation capability may be a possible causative mechanism for this elemental diet-induced muscle damage.
The inhibitory effect of FR-118487, a potent angiogenesis inhibitor, on neovascularization induced by the VX2 tumor was confirmed in a rabbit corneal assay. The antimetastatic effect of FR-118487 was also investigated in 21 rabbits. Spontaneous liver metastases were induced by VX2 tumor cell implantation into the ascending colonic wall. FR-118487 was then infused continuously into the portal vein for 7 days after resection of the primary lesion at a dose of 1 mg/kg/day (FR-1 group) or 3 mg/kg/day (FR-3 group). The incidence of liver metastases was 71.4%, occurring in 5 of 7 rabbits, in each of the FR-1 and FR-3 groups, compared with 100%, being all of 7 rabbits, in the control group. The number of metastatic foci tended to be less in the FR-1 (31.0 +/- 36.0) and FR-3 (24.6 +/- 45.1) groups than in the control group (83.7 +/- 73.9) and the weight of metastatic foci was significantly less in the FR-1 (1.4 +/- 1.8 g) and FR-3 (1.3 +/- 2.0 g) groups than in the control group (6.5 +/- 4.9 g) (P < 0.05). However, leakage of the colonic anastomosis and body weight loss were limited to the FR-3 group. These results suggest that the continuous intraportal infusion of FR-118487 at 1 mg/kg/day suppressed liver metastases by inhibiting angiogenesis, without producing any adverse effects.
Laparoscopic cholecystectomy (LC) was safely performed for cholelithiasis in a 4-year-old boy who had a long transverse operative scar in the upper abdomen as a result of intestinal surgery performed during the neonatal period. The adhesions beneath the scar were sharply divided and sometimes coagulated, and additional working ports were subsequently placed as the adhesiolysis proceeded. LC was performed in the usual fashion using 5-mm titanium clips, and his postoperative course was uneventful. This case report serves to demonstrate that laparoscopic surgery is feasible even for pediatric patients who have undergone previous major intraabdominal surgery.
BACKGROUND & AIMS: Regenerating gene (Reg) has been isolated from rat regenerating pancreatic islets, and Reg protein is mitogenic to islet cells. We have recently shown that Reg gene and Reg protein are expressed in gastric enterochromaffin-like (ECL) cells. This study aimed to clarify whether gastrin enhances Reg protein production in ECL cells and whether Reg protein is mitogenic to gastric mucosal cells. METHODS: Reg gene expression in response to acute and chronic hypergastrinemia was investigated in rats. Immunohistochemical studies, Northern blotting, and in situ hybridization were performed to investigate the expression of Reg protein and Reg gene. The direct effect of gastrin on Reg gene expression was investigated using isolated ECL cells, and the trophic effect of Reg protein on cultured gastric epithelial cells was assessed by [3H]thymidine uptake. RESULTS: Both chronic hypergastrinemia and short-term gastrin administration stimulated Reg gene expression and Reg protein production in fundic mucosa. Reg gene expression was also augmented in isolated ECL cells after incubation with rat gastrin. Reg protein was mitogenic to cultured rat gastric epithelial cells. CONCLUSIONS: Gastrin stimulates the production of Reg protein in gastric ECL cells, which may be involved in the gastrin-induced gastric mucosal cell growth.
Adhesion molecules and cytokines are known to be involved in the formation of acute gastric mucosal injury. However, it is not clear whether the gastric mucosal cells express these molecules and modulate the inflammation. To clarify whether gastric mucosal cells express intercellular adhesion molecule-1 (ICAM-1) and proinflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha), interleukin-1-alpha (IL-1-alpha), and cytokine-induced neutrophil chemoattractant-2-beta (CINC-2-beta)) in the formation of gastric mucosal injury, we have used rat indomethacin-induced gastric mucosal lesions as an in vivo model. The gene expression of all cytokines and ICAM-1 increases at the early stages of indomethacin-induced gastritis (TNF-alpha and IL-1-alpha gene expression began to increase earlier than that of ICAM-1 and CINC-2-beta) and can mainly be detected in the gastric epithelial layer. To further identify the source of those molecules, the epithelial cells were separated into seven fractions according to their sizes by a counterflow elution. ICAM-1 and CINC-2-beta gene expressions are particularly enhanced in the middle-sized cell fractions that are rich in gastric mucous-producing cells. The effect of TNF-alpha or IL-1-alpha on the gene expression of ICAM-1 and cytokines was examined by using RGM-1 cells as a model for gastric mucosal cells. RGM-1 cells show an augmented ICAM-1 and proinflammatory cytokine expression in response to TNF-alpha or IL-1-alpha stimulation. Moreover, immunohistochemical staining also reveals an increase in ICAM-1 and CINC protein production in RGM-1 cells in response to TNF-alpha stimulation. We conclude that gastric mucosal cells express various cytokines and an adhesion molecule during the formation of acute gastric mucosal injury and that they may modulate the inflammation.
BACKGROUND/PURPOSE: Hirschsprung's disease (HD, HSCR) is one of the most common diseases in the field of pediatric surgery. It is well known that the aganglionic bowel is primarily a causative factor of dismotility of distal narrow segment. Recent studies have shown that mutations in endothelin-B receptor (EDNRB), endothelin-3, RET, glial cell line-derived neurotrophic factor (GDNF) genes are responsible for the occurrence of congenital aganglionosis. Here, the authors describe two new mutations of the EDNRB gene in Japanese patients with HD. RESULTS: One patient had a heterozygous point mutation at the splice donor site of intron 3, leading to premature termination of translation of EDNRB mRNA. Another patient has a heterozygous missense mutation (N1041) in exon 1, but the same mutation was found in two of 50 normal individuals, so the mutation may be a noncausative polymorphism of the EDNRB gene. CONCLUSION: These results provide further evidence that a spectrum of different mutations within the EDNRB gene are responsible for HD.
BACKGROUND/PURPOSE: The matrix metalloproteinases (MMPs) are responsible for degradation of the extracellular matrix. The MMPs and their specific tissue inhibitor metalloproteinases (TIMP) have been associated with tumor cell invasion and metastasis in a number of adult tumors. This study was carried out to detect their expression pattern in neuroblastoma and to evaluate whether they have any association with tumor progression and clinical outcome. METHODS: Cryostat sections of tumor tissues were collected from 31 patients with neuroblastoma, and immunohistochemical staining of MMP-2, MMP-9 and TIMP-2 with specific antibodies was performed according to labelled streptavidin-biotin method. RESULTS: MMP-2 and MMP-9 were coexpressed in neuroblastoma and exhibited an intratumor variability of staining intensity. MMP-2 and MMP-9 staining were confined mostly to the peritumoral stromal tissues rather than tumor cells and found positive in 80.6% cases and 71.0% cases, respectively. MMP-2 and MMP-9 immunoreactivity had no association with mass screened cases or with age of the patients. Increased expression of MMP-2 in stromal tissues of neuroblastoma had significant association with advanced clinical stages (chi2 test, P < .05). However, the expression of MMP-9 in neuroblastoma had no association with clinical stages and prognosis. However, TIMP-2 staining was confined mostly to the neoplastic cell cytoplasm, stromal tissue, and to the endothelial cells and accounted for 58.0% positivity. Decreased expression of TIMP-2 also had significant relationship with advanced clinical stages (chi2 test, P < .05). Kaplan-Meier survival curve showed that either increased expression of MMP-2 or decreased expression of TIMP-2 had relationship with poor clinical outcome. CONCLUSIONS: In neuroblastoma, stromal tissues are actively involved in the complex interaction between MMP-2 and TIMP-2 in extracellular matrix degradation during tumor progression, and TIMP-2 expression is inversely correlated with the corresponding MMP-2. An early detection of their expression pattern by immunohistochemistry in neuroblastoma may provide prognostic informations in clinical practice.
A 2-year, 9-month-old boy had an umbilical fistula after repair of an inguinal hernia at 8 months of age. Fistulography findings showed a duct running from the umbilicus toward the inguinal wound. Pathological finding of the surgically removed fistula demonstrated granulomatous tissues containing silk ligature. Acquired umbilical fistula is a rare complication of inguinal herniorrhaphy. Its clinical details as well as a review of the previously reported four cases are presented.
BACKGROUND: The prognosis of hepatoblastoma is poor unless the tumor is completely resected. Various types of chemotherapy have been developed to increase its resectability. Recently, transcatheter arterial chemoembolization (TACE) has been developed for the treatment of unresectable adult hepatoma with favorable results. The authors applied this procedure to hepatoblastoma in infants and children. METHODS: TACE was performed in eight hepatoblastoma cases. After an intraarterial catheter was inserted into the main feeding artery of the tumor, injection of adriamycin or THP-adriamycin (20 to 30 mg/m2) dispersed in lipiodol and cisplatin (40 to 60 mg/m2) followed by embolization using Gelfoam pieces was performed. Effects of TACE were evaluated according to shrinkage of tumor mass on imaging examinations, alpha-fetoprotein (AFP) levels, and pathological findings of the surgical specimens 4 weeks after TACE. RESULTS: A marked reduction in tumor size associated with a decrease in AFP level occurred 1 month after the treatment. Tumor shrinkage ranged from 0.9% to 45.0% with a mean value of 25.8%. AFP levels decreased by 0.2% to 11.9% with a mean level of 4.6% from initial levels. In addition, there was no marked chemotherapeutic agent-induced toxicity noted during the observation period. Resection of the tumors was performed safely after TACE in all cases. Pathological examination showed massive necrosis in the surgical specimens, and the mean percentage of necrotic area within the tumor was 71.1%. Two patients died of extensive lung metastasis 2 months and 3 years after the operation, respectively. The remaining six were doing well and free of disease at a mean follow-up period of 50 months. CONCLUSION: TACE is an effective, safe, and useful method for the initial treatment of hepatoblastoma.
PURPOSE: This study was performed to clarify whether infants with congenital dilatation of the bile duct (CDBD) have any specific characteristics in comparison with older children. METHODS: Of 153 cases with CDBD treated at our institution between 1959 and 1997, 34 (22.2%) were infants less than 1 year of age. The control group consisted of 46 children between 1 and 4 years of age. Symptoms, laboratory data, and histological findings were compared between these two groups. RESULTS: As the initial symptoms, abdominal pain was not present in infantile cases, with a significant difference from the older children, and a significantly higher incidence of abdominal mass and acholic stools was noted in infantile cases. Laboratory data of serum aspartate transaminase and amylase level and amylase concentration in the bile of the common bile duct were significantly lower in the infant group than in the older children. The ratio of morphological type of cystic to cylindrical dilatation was 33 to 1 in infants with a significant difference from the control group. CONCLUSION: Infantile cases of CDBD, which mostly have cystic type dilatation, in contrast to older children, are likely to present with abdominal mass. Pancreatitis with abdominal pain related to reflux of pancreatic juice into the biliary duct appears to be uncommon in infantile cases.
BACKGROUND/PURPOSE: It is reported that the main mechanism responsible for gastroesophageal reflux (GER) is transient lower esophageal sphincter (LES) relaxation in children. However, the effect of Nissen fundoplication on transient LES relaxation has not been investigated in children. This study examined the effect of Nissen fundoplication on motor patterns of the LES in children with pathological GER. METHODS: Esophageal manometry and pH were recorded concurrently for 2 hours after administration of apple juice (10 mL/kg). In seven children documented to have pathological GER by prolonged esophageal pH monitoring (%time pH less than 4.0>5.0), studies were performed preoperatively and 1 to 3 months after surgery. RESULTS: Nissen fundoplication virtually eliminated reflux in all patients. Percentage of time pH was less than 4.0 reduced from 15+/-9 to 0+/-0. Basal LES pressure did not change significantly (pre, 21+/-10 mm Hg v post, 27+/-9 mm Hg). The number of transient LES relaxation reduced significantly from 13+/-4 to 7+/-7, and the mean nadir LES pressures during swallow-induced LES relaxation and transient LES relaxation increased significantly from 1+/-1 mm Hg to 13+/-5 mm Hg and from 0+/-0 mm Hg to 11+/-7 mm Hg, respectively. CONCLUSIONS: Our findings suggest the antireflux effects of Nissen fundoplication may be based on changes of LES motor patterns that result in incomplete LES relaxation and reduction of the number of transient LES relaxation.
BACKGROUND/PURPOSE: Gastroesophageal variceal bleeding is a serious and difficult problem in the long-term management of biliary atresia (BA). Recently, endoscopic approaches have been attempted to manage this problem. The authors have attempted endoscopic variceal ligation (EVL), a less invasive procedure than endoscopic sclerotherapy. METHODS: In the past 5 years, 66 EVL procedures using standard flexible endoscope with a diameter of 9 mm (type p-30, XQ200, or XQ240; Olympus, Tokyo, Japan) were performed in 30 separate sessions on 11 postoperative BA patients. The mean age of the children was 7.8 (range, 3 to 15) years. The EVL device was a small elastic O-ring or a loop ligator. RESULTS: EVL was performed for emergency hemostasis in two patients and prophylaxis for impending rupture in nine with large, blue varices, or with red spots on the variceal surface. During the initial procedure, all varices were ligated successfully, and reduction in size was noted. Of eight patients who were examined 7 to 14 days after treatment, seven (87.5%) had improved. Eight of 11 patients (72.7%) were finally cured or at least had improved after one to seven sessions of EVL. However, three patients did not show improvement after four to seven sessions because of the reappearance of the varices, development of distal lesions such as gastric varices, and acute gastric mucosal lesions. A technical complication encountered was a slippage of the O-ring in one patient. A technical difficulty was seen in ligating the giant gastric varix in one patient. There was no deterioration of liver function induced by EVL in this entire series. CONCLUSIONS: EVL is an effective and feasible treatment of gastroesophageal varices in postoperative BA patients. However, reappearance or reactivation of the varices or emergence of the more distal lesions is likely to occur even after repeated EVL.
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Gastrin is a pivotal humoral factor which regulates gastric acid secretion through its receptors. There is no report, however, concerning the age-related changes of gastrin receptor gene expression in the stomach. Northern blot analysis and in situ hybridization were performed to clarify the changes of gastrin receptor expression during the aging. In situ hybridization clarified that gastrin receptor mRNA was expressed mainly in enterochromaffin-like (ECL) cells in adult rat gastric mucosa. With aging, gastrin receptor gene expression in the stomach increased with the concomitant increase in histidine decarboxylase mRNA. Since histidine decarboxylase is a marker of gastric ECL cells, the augmented gastrin receptor mRNA in aged rats may be caused by the increased ECL cells in gastric mucosa during the aging.
OBJECTIVES: We examined the circadian variations in atrioventricular (AV) conduction properties during atrial fibrillation (AF) by a technique based on the Lorenz plot of successive ventricular response (VR) intervals and analyzed their relations with clinical features. BACKGROUND: The VR interval in chronic AF shows circadian variation, which is attenuated in patients with an increased risk of death. Although the VR interval is determined by the dynamic processes in the AV node randomly stimulated by rapid atrial activity, the circadian variations of the AV conduction properties related to this mechanism are unknown. METHODS: In 48 patients with chronic AF, Lorenz plots were generated on overlapping sequential segments of 512 VR intervals in 24-h ambulatory electrocardiograms. For each scatter plot, the 1.0-s intercept of the lower envelope (LE1.0) of the plot and the degree of scatter above the envelope (root mean square difference from the envelope [scattering index]) were measured for estimating AV node refractoriness and concealed AV conduction, respectively. RESULTS: In all patients, a significant circadian rhythm was observed for the average VR interval, LE1.0 and scattering index, with an acrophase occurring at night. The mesor, amplitude and acrophase of LE1.0 and the scattering index closely and independently correlated with the corresponding rhythm variables of the average VR interval (partial r2 0.98, 0.86 and 0.68 for LE1.0 and 0.98, 0.92 and 0.92 for scattering index). The amplitudes of these measures were lower in patients with congestive heart failure (CHF) even after adjustment for the effects of age, duration of AF, medications, left atrial diameter and blood pressure (p < 0.01 for all). CONCLUSIONS: These results suggest that 1) both AV node refractoriness and the degree of concealed AV conduction during AF may show a circadian rhythm; 2) the circadian rhythms of these properties may independently contribute to the circadian variation of the VR interval; and 3) these circadian rhythms may be attenuated in patients with CHF.
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