[Therapeutic administration of trace elements and manganese poisoning].
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Publications and source records attributed to S Suita.
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Morphometrical analyses of the immunohistochemical expression of bombesin, which is one of the peptides produced by pulmonary neuroendocrine (PNE) cells, were carried out on the bronchioles of human congenital diaphragmatic hernia (CDH) neonates, and the findings were then compared with those in a gestational and postnatal age-matched control group. As a result, no difference was found in the number of bombesin-positive cells between the lungs of the control group and the unaffected side lungs in the CDH group except for the ratio of the bombesin-positive cells per unit of the bronchiolar surface area (P < 0.05). However, compared with the lungs in the control group, the affected side of the lungs in the CDH group showed a significant increase in the expression of bombesin, namely, the ratio of the bombesin-positive cells per bronchiole (P < 0.05), the ratio of the bombesin-positive cells per unit perimeter of the bronchioles (P < 0.05), and the ratio of the bombesin-positive cells per unit of the bronchiolar surface area (P < 0.01). These results thus suggest that hyperplasia of the PNE-cell system in the lungs of the CDH cases, especially on the affected side, exists in human fetuses. We also further speculate that PNE cells may thus play a role in the problems associated with CDH during intrauterine life in human beings.
The prevalence of Helicobacter pylori infection in postoperative patients with biliary atresia (BA) was investigated in relation to esophageal varices, portal-hypertensive gastropathy (PHG), and peptic ulcer disease (PUD) in 25 Japanese patients (10 boys and 15 girls) aged from 16 months to 20 years. Gastric biopsy specimens obtained during endoscopy were used for both the rapid urease test and modified Giemsa staining. The patients were classified into three groups according to liver function: 15 in group A (total bilirubin [TB] < 1.0 mg/dl), 7 in group B (1.0 </= TB < 2.0 mg/dl), and 3 in group C (TB >/= 2.0 mg/dl). Esophageal varices were found in 19 patients (60% of group A and all patients in groups B and C) and PHG in 3 group B patients. However, no gastric or duodenal ulcers were found in any case. Only 2 patients (8%) had H. pylori colonization of the gastric mucosa. Both, however, belonged to group A, and the degree of chronic neutrophilic infiltration of the mucosal layer was as mild as that of the other patients. The prevalence of H. pylori infection and PUD in postoperative patients with BA was quite low, and a pathological relationship with the severity of liver disease could not be determined in these patients.
BACKGROUND/PURPOSE: Intestinal dysmotility, which usually has been encountered in the severely dilated proximal segment, is an important problem in postoperative management of patients with intestinal atresia (IA). Changes of enteric nerves had been histochemically examined in both the proximal and distal segments of IA, but a systemic immunohistochemical analysis is still lacking. The aim of this study was to examine precisely alterations of neuronal and muscular elements and pacemaker cells in intestines from patients with IA. METHODS: Resected intestines were obtained from 5 patients with ileal atresia, 3 patients with jejunal atresia, and 3 controls without gastrointestinal diseases (congenital diaphragmatic hernia). All specimens were immunochemically stained with a monoclonal antibody to alpha-smooth muscle actin (SMA) as a smooth muscle marker, polyclonal antibodies to protein gene product (PGP) 9.5 as a general neuronal marker, and to c-kit protein as a maker of intestinal pacemaker cells. In addition, all specimens also were stained by NADPH-diaphorase (NADPH-d) to know the distribution of inhibitory nitrergic nerves. RESULTS: A hypoplasia of the myenteric ganglia and a marked reduction of intramuscular nerve fibers, including nitrergic neurons, were observed in the dilated proximal segment of IA. C-kit-positive cells were localized around the myenteric plexus, but rarely found within the muscularis propria in the proximal segment. The distribution of nerves and c-kit-positive cells in the distal segment was comparable with that seen in controls. A reduced staining intensity for alpha-SMA was mainly observed in the hypertrophic circular muscle layer of the proximal segment. CONCLUSIONS: A hypoplasia of intramural nerves and pacemaker cells was seen predominantly in the proximal segments of IA. Hypertrophy and reduced immunoreactivity for alpha-SMA also were observed in the circular muscle layer of the proximal segment. These alterations of the proximal segment may thus contribute to the postoperative intestinal dysmotility in IA cases.
BACKGROUND/PURPOSE: Nitric oxide (NO) has been considered one of the putative neurotransmitters of nonadrenergic, noncholinergic inhibitory neurons. To examine the effect of transplantation on NO neurons in the intestine, the distribution of NO neurons was examined and compared with that of peptide-containing neurons. METHODS: A jejunal graft measuring about 20 cm was harvested from a Lewis rat, syngeneically transplanted as a Thiry-Vella loop, and later was replaced to the recipient small bowel 20 days after transplantation. Tissue specimens of the grafts were taken on days 1, 3, 6, 10, and 20, and 1 year after transplantation (n = 5 each). The distribution of the neurons was examined immunohistochemically, using antisera against protein gene product 9.5 (PGP 9.5, general neuronal marker), brain nitric oxide synthase (bNOS), vasoactive intestinal polypeptide (VIP), and substance P. In addition, NADPH diaphorase staining also was performed to visualize NO neurons. RESULTS: In the PGP 9.5 immunoreactivities, no significant difference in the distribution was observed among the controls and on any day after transplantation. However, the NADPHd activities markedly decreased in muscle layers, especially in the deep muscular layer on day 1 and 3, but quickly recovered by day 6. The distribution of bNOS immunoreactivities was almost same as that of NADPHd staining. The VIP and substance P immunoreactivities also decreased on day 1, and thereafter gradually recovered, and then became normal on day 20. CONCLUSIONS: Both the NO and peptidergic neurons markedly decreased just after transplantation, and the NO neurons recovered faster than the peptidergic neurons. These findings suggested that NO neurons might play an important role in the adaptation process of the graft in the early period after transplantation.
BACKGROUND/PURPOSE: Ascending testes, which normally are located at the bottom of the scrotum in early infancy and later ascend back out of the scrotum, have been reported by several investigators. However, little is known about the effect of the division of the genitofemoral nerve (GFN) on testicular ascent as boys grow. The purpose of this study is to investigate whether the division of the proximal genitofemoral nerve in prepubertal rats induces testicular ascent in adulthood. METHODS: Thirty-day-old Wistar King A Rats (n = 27) underwent a unilateral proximal GFN transection on either the right or left side. At 150 days of age, the rats were killed, and their testicular position was examined. The length of the processus vaginalis was measured, and the testes were removed and weighed. Sham-operated rats were used as controls (n = 10). Student's t and the chi2 test were used for the statistical analysis. RESULTS: At 150 days of age, 21 of the 27 operated rats (77.8%) showed unilateral testicular ascent on the operated side. All testes were located at the bottom of the scrotum in sham-operated control rats (20 testes). Both the length of the processus vaginalis and the testicular weight were decreased significantly more on the operated side than in the sham-operated rats. CONCLUSIONS: These findings suggest that the proximal division of the genitofemoral nerve in prepubertal rats may induce a relative ascent of the testis by preventing the growth of the processus vaginalis in adulthood. In patients with such ascending testes, an abnormal development or accidental trauma of the genitofemoral nerve may be involved in testicular ascent.
PURPOSE: The aim of this study was to identify the most appropriate timing for surgery in newborns with choledochal cysts. METHODS: The clinical and histological data of 8 newborn cases of choledochal cysts (newborn group) were compared with 45 cases that were diagnosed later than the newborn period (late group). RESULTS: The mean and standard deviation of age at diagnosis was 0.4+/-0.4 months and 43.4+/-37.8 months in the newborn and late group, respectively. The age at operation was significantly earlier in the newborn group than in the late group (4.9+/-4.5 months v54.7+/-47.0 months). Although no significant difference in the time that elapsed between the operation and the onset of symptoms between the newborn and late groups (4.5+/-4.7 months v11.3+/-21.1 months), the serum bilirubin level (4.6+/-3.8 mg/dL v1.8+/-3.4 mg/dL) and the grade of liver fibrosis (2.0+/-0.8 v1.1+/-0.8) were significantly higher in the newborn group than in the late group. CONCLUSION: The newborn group should be considered as a special group of patients with different clinical course and pathology than those of the late group, which necessitate the early surgical intervention to prevent progression of liver fibrosis.
BACKGROUND/PURPOSE: The N-myc amplification status in neuroblastoma has been evaluated previously for the whole tumor by the Southern blot method. The aim of this study is to evaluate the effectiveness of the fluorescence in situ hybridization (FISH) method to analyze N-myc amplification in neuroblastoma and compare the findings with those using the Southern blot method. METHODS: In 26 neuroblastoma primary tumors and metastatic lesions, the N-myc amplification status was evaluated by both the Southern blot method and FISH method. RESULTS: Of the 22 samples with no N-myc amplification using Southern blot, no cells with N-myc amplification using FISH were present in 21 of the samples. However, one metastatic liver lesion showed 16% of the nuclei to display more than 10 copies of N-myc based on FISH analysis. In the 4 remaining samples with N-myc amplification using the Southern blot method (17 copies, 15 copies, 6 copies, and 3 copies), the rates of cells with more than 10 copies of N-myc based on a FISH analysis were 79%, 68%, 94%, and 9%, respectively. CONCLUSIONS: The FISH method can detect more accurately N-myc amplification than the Southern blot method either when the rate of cells with N-myc amplification is low or intratumor heterogeneity is present.
BACKGROUND/PURPOSE: Infants with congenital diaphragmatic hernia have pulmonary hypoplasia resulting in persistent pulmonary hypertension of neonates (PPHN), which is the main contributor to both high mortality and morbidity. The pulmonary artery bed in patients with congenital diaphragmatic hernia (CDH) is underdeveloped and is very sensitive to slight stimuli. It is, therefore, vital to avoid any factors that might increase pulmonary vascular resistance during the perinatal treatment of these patients. Recently, fetal anesthesia for perinatal stabilization in patients with CDH has been reported. However, the efficacy of this method remains controversial. The aim of this study is to analyze the benefits of fetal stabilization using fetal anesthesia in patients with CDH. METHODS: The authors have seen 9 cases of antenatally diagnosed CDH and attempted fetal stabilization. The indication for fetal stabilization was a lung thoracic ratio of less than 0.2, without any severe associated anomalies. The protocol for fetal stabilization was (1) monitoring the fetal respiratory movement and heart beat by ultrasonography, (2) the administration of morphine (20 to 30 mg) and diazepam (5 mg) to the mother, (3) the confirmation of any interruptions in fetal movement followed by a cesarean section, (4) pancuronimum (0.5 mg) was given through the umbilical vessels, (5) intubation before clamping of the umbilical cord, and (6) high-frequency oscillatory ventilation (HFO) without bagging. RESULTS: The lung-thratic ratio (LTR) was between 0.06 to 0.17 (average, 0.10+/-0.04). Operation was performed in 7 of 9 patients at between 2.5 and 27 hours after birth. The overall survival rate was 66.7% (6 of 9). All of the patients who underwent operation within 5 hours after birth survived. CONCLUSIONS: Perinatal stabilization using fetal anesthesia was found to be effective in preventing PPHN and shortening the period of preoperative stabilization. It also improved the survival rate of patients with severe CDH.
PURPOSE: The correlation between the histological findings of the intrahepatic biliary epithelium and postoperative bile drainage in biliary atresia (BA) was investigated. METHODS: The patients with BA were classified into 2 groups, consisting of a good bile drainage group (GBD, n = 14, mean age at initial operation, 57.6+/-18.0 days) and a poor bile drainage group (PBD, n = 11, mean age at initial operation, 86.9+/-42.7 days). Liver specimens from an initial Kasai's operation were examined by immunostaining using anticytokeratin 7 (CK7) antibody and anti-MIB-1 antibody. The number of CK7-positive cells in the bile ductules was microscopically calculated within the 40-microm-thick interstitium along the limiting plate (LP), and the CK7-positive cell number per unit length of the LP was estimated. In addition, the MIB-1 index in bile ductules also was determined. RESULTS: The number of CK7-positive cells in PBD was significantly higher than that in GBD (167.6+/-45.6 v 117.8+/-32.4/ mm, P<.05). However, the MIB-1 index in biliary cells did not differ between the 2 groups. CONCLUSION: An increased number of intrahepatic bile duct epithelial cells in liver specimens at the initial operation may be a poor prognostic factor in BA and appears to depend on the duration of bile stasis rather than the degree of bile stasis.
OBJECTIVE: To evaluate the association of somatic growth from birth through diagnosis with the development of childhood cancer. METHODS: The weights and heights of 1718 children with cancers were determined and converted into standard deviation (SD) scores, both at birth and at diagnosis, by using the means and SD values of the general population. RESULTS: Among patients with neuroblastoma and acute lymphoblastic leukemia, the percentages of children with body weight and height over mean + 2 SDs were significantly higher at diagnosis than the expected value in the general population. The percentage of children with neuroblastoma and body weight over mean + 2 SD increased significantly from birth through diagnosis (P =.04). Although the medians of weight SD scores decreased from birth through diagnosis in patients with representative cancers except for neuroblastoma, the value significantly increased in patients with neuroblastoma diagnosed before 1 year of age (P =.03), especially in those whose cancer was detected by mass screening at 6 months of age (P <.01). CONCLUSIONS: Rapid somatic growth from birth through diagnosis in patients with neuroblastoma diagnosed before 1 year of age suggests a possible involvement of certain growth factors in these patients.
OBJECTIVE: To investigate whether prenatal maternal stress, considered to alter plasma testosterone concentration and induce a lack of testosterone surge in male rat fetuses, has any effect on the growth of the processus vaginalis and testicular descent in male offspring. MATERIALS AND METHODS: Pregnant rats were divided into two groups. In group 1, the rats were placed three times daily for 60 min each session in Plexiglas rat holders (13x6x8 cm) illuminated by two 150-W flood lights from day 14 to day 18 of gestation during the dark phase of the animals' light (12 h) and dark (12 h) cycle. In group 2, pregnant females were not handled and acted as controls. After birth, the anogenital distance of both the male and female rats was measured, and the length of the processus vaginalis was measured at 7 days of age in some rats. Thereafter, at 21, 24, 27 and 30 days of age, testicular descent was assessed in the remaining male rats. RESULTS: In group 1, at 21, 24, 27 days of age, testicular descent was delayed in the stressed rats compared with the control rats. At 30 days of age, five of 36 stressed male offspring showed abnormal testicular descent; three testes were in the superficial inguinal position and two were above the scrotum. Both the anogenital distance and the length of the processus vaginalis were significantly less in the stressed male rats than in the controls. CONCLUSIONS: Maternal stress induced a female-like anogenital distance in male rat fetuses, and caused delayed and abnormal descent of the testis, by inhibiting the growth of the processus vaginalis after birth. Prenatal stress may therefore be involved in the delay of testicular descent in neonatal rats by inducing a mild anti-androgenic effect in the fetus.
OBJECTIVE: To investigate whether the division of the proximal genitofemoral nerve (GFN) in neonatal rats induces testicular undescent or ascent in adulthood. MATERIALS AND METHODS: Neonatal Wistar King A rats underwent a unilateral proximal GFN transection on either the right or left side. At the age of 30 days, testicular descent was examined in all rats and the position of the testis recorded. The animals were allowed to develop further and the position of the testis re-examined at the age of 90-180 days, when the testes were removed and weighed. Sham-operated rats were used as controls. RESULTS: At the age of 30 days, four of the 46 (9%) operated rats showed a unilateral undescended testis on the operated side. At the age of 90-180 days, 43 rats were re-examined (three rats died before re-examination); 34 (79%) of these rats showed undescended testes on the operated side. The occurrence of cryptorchidism was significantly higher in the 90-180-day-old mature rats than in 30-day-old prepubertal rats (P<0.01). The mean (sd) weight of the undescended testes, at 2.36 (0.21) mg/g body weight, was significantly less than that of the contralateral scrotal testes, at 3.83 (0.23) mg/g; P<0.01) and of the control testes at the age of 90-180 days. In the sham-operated rats, all testes were located at the bottom of the scrotum at 30 days of age and no rats showed any testicular ascent thereafter. CONCLUSIONS: The proximal division of the GFN in neonatal rats not only causes inguinoscrotal testicular maldescent but may also induce testicular ascent in adulthood. Testicular ascent may thus be caused by some intrauterine disorders of the GFN in patients with ascending testis.
The occurrence of primary lung cancer is rare in childhood. The case of an 11-year-old boy with primary lung cancer is presented in this report. He had a substantial family history of cancer. His chief complaint was coughing with right chest pain. A chest radiograph showed a coin lesion in the right lower lung. A right lower lobectomy revealed a squamous cell carcinoma (stage IIIA at Japanese TNM classification). Systemic chemotherapy using cisplatin, vindesine, THP-adriamycin and cyclophosphamide was performed. Six months after surgery, a recurrent tumor occurred. An analysis of the familial cancer related genes (p53 gene and mismatch repair gene) showed no abnormality.
The postoperative intestinal dysmotility seen in intestinal atresia (IA) is usually found in association with a dilatation of the proximal intestinal segment, but the etiology of this disorder is not yet fully understood. A chick IA model was made by cutting the postumbilical midgut on d 11 in ovo. The operated chicks were euthanized 2 d after hatching. The samples were divided into two groups according to the extent of the dilatation of proximal ileal segments. Cryostat sections were processed for immunohistochemistry by the use of antisera to protein gene product 9.5, vasoactive intestinal polypeptide, substance-P, and alpha-smooth muscle actin and were also stained by NADPH-diaphorase. Tn highly dilated proximal segments, a decreased number of protein gene product 9.5-positive fibers was found in both the circular muscle and submucous layers. The number of nerve fibers positive for vasoactive intestinal polypeptide, substance-P, and NADPH-diaphorase also decreased in the circular muscle layer, particularly in the deep muscular plexus. Hypertrophy and an alteration of the staining intensities in the circular muscle layer were also revealed by a-smooth muscle actin staining. The nerve distribution of the distal segments was indistinguishable from that of the age-matched controls and the sham-operated group. Abnormalities in the intramural nerves are only found in the proximal ileal segment of the IA models. The abnormal nerve distribution of the proximal segment might thus be implicated in the postoperative dysmotility of the intestine in IA.
The efficacy of granisetron hydrochloride 20 microg/kg and 40 microg/kg were compared using a cross-over method to determine the optimal dose in children with solid tumors receiving high-dose chemotherapy. Granisetron controlled the onset of vomiting in 17 of 23 patients (73.9%) who were given 40 microg/kg of granisetron, while 8 of 21 patients (38.1%) were free of vomiting in the 20 microg/kg group. The average frequency of vomiting was 7.22 times in the 20 microg/kg dose versus 4.44 times in the 40 microg/kg dose. No safety problems were associated with either dose. The 40 microg/kg dose of granisetron appears to be more optimal.
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