Noboru Oyachi

Development of ovine fetal ileal motility: role of muscarinic receptor subtypes

OBJECTIVE In the preterm human fetus, immaturity of gastrointestinal (GI) motility contributes to impairment of oral feeding and an increased risk of necrotizing enterocolitis. In view of the limited knowledge of fetal GI motility development, and the primary role of the muscarinic system in adult GI motility, we examined the development of GI muscarinic receptor subtypes associated with ileal motility. STUDY DESIGN Ovine term fetal, newborn, and pregnant adult ileal longitudinal muscle contractile responses to muscarinic agonists (bethanechol) and muscarinic nonspecific (atropine) and subtype specific-antagonists (M1-M4) were examined in organ baths. Immunohistochemical analysis of ileal muscle muscarinic receptor subtypes was correlated with contractile responses. RESULTS Bethanechol induced a concentration-dependent ileal contraction at all 3 age groups. Adult ileal maximal tension was 2-fold higher than that of the fetus and newborn, while 50% effective concentration (EC(50)) was similar at all ages. Atropine (10(-6)mol/L) inhibited contractility in fetal (67%+/-7%), newborn (82%+/-5%), and adult (97%+/-2%) in an age-dependent manner. The M3 antagonist exhibited robust inhibition at all age groups while the M2 antagonist demonstrated enhanced inhibition in the fetus. Immunohistochemical analysis indicated coexpression of subtype receptors in fetal, newborn, and adult ileal smooth muscle with increasing expression with advancing age. CONCLUSION These results demonstrate a specific developmental pattern of muscarinic receptor subtype expression. Knowledge and/or alterations of GI motility regulation may aid in the treatment of the preterm fetus or newborn.

Elevated Plasma Corticotrophin Release Factor Levels and In Utero Meconium Passage

Intrauterine meconium (MEC) passage and aspiration may result in significant newborn morbidity, though there is little understanding of the physiologic mechanisms for MEC passage. We hypothesized that stress induces fetal MEC passage via corticotrophin releasing factor (CRF), a known mediator of colonic motility in adult rats. Pregnant rats at e22 were subjected to acute hypoxia or normoxia for 35 min, after which rats were anesthetized and fetuses operatively delivered. Amniotic fluid bilirubin and intestinal alkaline phosphatase were measured as markers for MEC passage, and fetal and maternal plasma CRF and corticosterone levels determined. Hypoxic stress induced defecation in all dams and provoked visible MEC passage in all fetuses. Amniotic fluid bilirubin content was significantly higher in hypoxic fetuses versus controls (1.064 ± 0.101 versus 0.103 ± 0.003 O.D. at 410 nm) and intestinal alkaline phosphatase was consistently elevated in MEC stained amniotic fluid. Hypoxia significantly increased plasma CRF (maternal, 82 ± 5 to 196 ± 14 pg/mL; fetal, 284 ± 15 to 1523 ± 185 pg/mL) and corticosterone (maternal, 417 ± 50 to 1150 ± 50 ng/mL; fetal, 96 ± 5 to 182 ± 10 ng/mL) compared with controls. In view of the known action of CRF in adult colonic motility, these results suggest that hypoxic stress-mediated MEC passage in term fetal rats is mediated by a CRF dependent pathway.

Two different types of infantile renal cell carcinomas associated with tuberous sclerosis.

Renal cell carcinoma (RCC) associated with tuberous sclerosis (TSC) has been reported in adult patients; however, this association is rare in children. We have encountered 2 different types of RCCs in infants who developed TSC later in childhood. The pathologic diagnoses were papillary RCC in one infant and a clear cell-type RCC in the other. Gene analysis showed that both the patients had a mutation in TSC2 gene on chromosome 16.

Costal BCG osteomyelitis developing 1 year after BCG vaccination

Reported here is the case of a 15‐month‐old boy with costal osteomyelitis due to the bacillus Calmette–Guérin (BCG) vaccine against tuberculosis. Mild complications of this vaccine, such as localized abscess and regional lymphadenitis, are occasionally recognized, but its association with osteomyelitis is extremely rare.

Anticholinergic suppression of fetal rabbit upper gastrointestinal motility

Objective: At birth the newborn digestive tract must assume the responsibility of assimilating nutrients for survival. Immature gastrointestinal motility in the neonate may result in impaired feeding and nutrition. Newborn gastrointestinal motility development requires the expression and functional maturation of gastrointestinal receptors. To explore the timing of fetal responses to gastrointestinal cholinergic motility agents, we assessed the effect of the anticholinergic agent atropine in the late-gestation rabbit fetus. Methods: Seven pregnant New Zealand White rabbits were studied at day 30 of their normal 31-day gestation. In each litter, two fetuses were selected as study (n = 14) and two as control (n = 14). Under ultrasound guidance, a spinal needle was percutaneously inserted through the maternal uterus into the fetal stomach and 0.5 ml of gastric content was aspirated. Fluorescein, labelled with colored microspheres, and either atropine (0.04 μg/g fetal body weight) or normal saline were injected in a total volume of 0.5 ml. Two hours after injection, fetuses were delivered, the small intestine harvested, and the total small intestinal length and the distance the gastrointestinal fluorescein travelled were measured by ultraviolet light optical density. The fluorescein travelled distance and the per cent motility, defined as the length of fluorescein travelled divided by the total length of the small intestine, were calculated. Results: All fetuses survived the intragastric injection. Mean fetal body weight at delivery was 44.2 ± 6.7 and 46.8 ± 7.2 g in atropine and control fetuses, respectively. The fluorescein travelled distance (15.4 ± 4.2 vs. 19.0 ± 4.3 cm;. p < 0.01) and per cent motility (51.0 ± 8.9 vs. 63.8 ± 11.7%; p < 0.01) of atropine-treated fetuses were significantly lower than those of control fetuses. Conclusion: Fetal upper gastrointestinal motility is suppressed in response to intragastric atropine. These results indicate that fetal gastrointestinal cholinergic receptors are expressed and functional in the term (0.97 gestation) rabbit fetus. In utero administration of cholinergic agonists/antagonists may potentially modulate fetal gastrointestinal motility and absorption of amniotic fluid water and solutes.

Ontogeny of cholinergic regulation of fetal upper gastrointestinal motility

Objective: In the fetal rabbit immediately prior to birth (day 30; 0.97 gestation), intragastric atropine suppresses upper gastrointestinal (GI) motility, indicating that cholinergic receptors are expressed and functional at birth. To explore the developmental timing of upper GI cholinergic receptor function, we assessed the effect of intragastric atropine administration in rabbit fetuses during the last 10% of gestation. Methods: Pregnant rabbits were studied at day 27, day 28 and day 29 of their normal 31-day gestation. In each litter, two fetuses were selected as study fetuses and two as control fetuses. Under ultrasound guidance, fluorescein and either atropine (0.04 μg/g fetal body weight) or normal saline were injected into the fetal stomach. Two hours after injection, fetuses were delivered and the small intestine was harvested. The per cent motility was calculated as the fluorescein travel distance, which was measured by ultraviolet light optical density, divided by the total small intestinal length. Results: Fetal body weight, small intestinal length and per cent motility increased from day 27 to day 29 (p < 0.01). There were no differences in fetal body weight and small intestinal length between atropine and control groups. Atropine significantly decreased per cent motility (versus control values) in fetuses at day 29 and day 28 (56.1 ± 13.5 vs. 66.1 ± 11.7% and 59.7 ± 15.6 vs. 68.3 ± 11.7%, respectively; p < 0.05), but not at day 27 (52.4 ± 12.9 vs. 52.8 ± 11.2%). Conclusions: These results indicate that upper GI functional cholinergic receptors develop between 0.87 and 0.90 of rabbit gestation. Extrapolation to human development suggests that reduced GI motility in preterm human infants results, in part, from immature GI cholinergic receptors.

Mechanisms of Meconium Passage: Cholinergic Stimulation of Electromechanical Coordination in the Fetal Colon

Objective: Fetal gastrointestinal function develops in utero, with evidence of enhanced motility near-term. Although colonic passage of meconium in utero may be associated with fetal maturation or stress, little is known of the mechanisms potentiating motility. We assessed the effect of bethanechol, a cholinergic prokinetic agent, on colonic muscle muscular contractile and electromyogram (EMG) activity in the near-term ovine fetus. Methods: Near-term (130 days, n = 8) singleton ovine fetuses were chronically prepared with vascular catheters and three sets of miniature strain gauges and bipolar EMGs on the serosal surface of the transverse colon, left colic flexure, and distal colon. Following a 60-minute control period, fetuses received intravenous bethanechol (60 μg/kg, Low-Beth; 120 μg/kg, High-Beth) at 60 and 180 minutes. Colonic activity was recorded digitally and analyzed for short-duration (2<SHORT< 15 seconds) and long-duration (15<LONG< 120 seconds) strain gauge and EMG contractions. Data were expressed as means ± SEM and analyzed using one-way analysis of variance (ANOVA) and paired t test. Results: During the control period, there was significantly greater SHORT versus LONG strain gauge contractions in all segments (P <. 05). As compared to control values, Low-Beth and High-Beth signficantly increased SHORT strain gauge contractions in the transverse colon (160 ± 13 to 201 ± 36 and 307 ± 74 spikes/30 min, respectively, P <.05), although not in left colic flexure or distal colon. Bethanecol did not affect LONG strain gauge contractions. SHORT-EMG and LONG-EMG spike bursts did not change in response to bethanecol (280 ± 20, 59 ± 2 spikes/30 min, respectively). Conclusion: Cholinergic stimulation of fetal sheep colonic activity at 0.9 gestation occurs in the transverse colon, but not the more distal left colic flexure or distal colon. The increased strain gauge, but not EMG activity, suggests that cholinergic stimulation improves electromechanical coordination in the fetal colon. We speculate that cholinergic-induced delivery of gastrointestinal contents to the distal colon evokes local contractile/expulsive mechanisms resulting in meconium passage.

Use of an appendicitis medical information sheet in the pediatric primary care system.

Accurate and prompt diagnosis is required for the primary evaluation of pediatric appendicitis. Among pediatricians and surgeons working in Yamanashi Prefecture, the pediatric appendicitis medical information (PAMI) sheet was edited in April 2011 to reflect the diagnostic results of the pediatric primary and emergency medical service and used as a referral document for surgical consultation to secondary hospitals.

Performance of the appendicitis medical information sheet in pediatric primary care system

Accurate and prompt diagnosis is required for the primary evaluation of pediatric appendicitis. Among pediatricians and surgeons working in Yamanashi Prefecture, the pediatric appendicitis medical information (PAMI) sheet was edited in April 2011 to reflect the diagnostic results of the pediatric primary and emergency medical service and used as a referral document for surgical consultation to secondary hospitals.

Dieulafoy lesion in a two-year-old boy: a case report

BackgroundMassive gastrointestinal bleeding in children, mostly caused by esophageal varices secondary to chronic liver disease, is uncommon. Dieulafoy lesion in the gastrointestinal tract is a rare but important cause of gastrointestinal bleeding; massive bleeding from this lesion can be fatal unless adequate treatment is promptly initiated. We report a case of gastric Dieulafoy lesion in a 2-year old successfully treated with endoscopic hemoclipping.Case presentationA 2-year-old Japanese boy was admitted to our department with sudden massive hematemesis. He had no significant past medical illness, and he was well just before the episode of hematemesis. A clinical examination revealed anemia (hemoglobin, 8.0 g/dl). The rapidly progressive anemia associated with massive hematemesis indicated the presence of an active bleeding in his upper gastrointestinal tract. We performed emergency gastroscopy under general anesthesia. The gastroscopy revealed the presence of an abnormal visible vessel with an adherent clot on the lower body of his stomach. No mucosal abnormality surrounding the lesion was noted; the lesion was thus diagnosed as Dieulafoy lesion. One hemostatic clip was placed on the Dieulafoy lesion and excellent hemostasis was obtained. He recovered without blood transfusion and was discharged 4 days post-endoscopy. He has recovered well with no recurrence of hematemesis.ConclusionsDieulafoy lesion is rare cause of sudden massive gastrointestinal bleeding in children. Nevertheless, it should be considered a differential diagnosis, even in babies. With advances in gastrointestinal endoscopy, as both a diagnostic and therapeutic modality, laparotomy secondary to gastrointestinal bleeding from Dieulafoy lesion has decreased in pediatric cases. Our case report demonstrates the feasibility of endoscopic hemoclipping for gastric Dieulafoy lesion in a child.