Enhanced expression of N-myc messenger RNA in neuroblastomas found by mass screening.

A substantial fraction of neuroblastomas found by mass screening have been suggested to regress spontaneously because of the high incidence of infantile neuroblastomas in the screening population. In this study, 70 neuroblastomas were analyzed for expression of proto-oncogenes related to neuronal differentiation to clarify the biological significance of proto-oncogene expression in the screening-positive and -negative tumors. The tumors consisted of 39 neuroblastomas found by screening (group 1), 16 non-N-myc-amplified neuroblastomas found by clinical symptom(s) (group 2), and 15 N-myc-amplified neuroblastomas found by clinical symptom(s) (group 3). The expression of c-src, trk A, and N-myc in tumor tissues was analyzed by quantitative RNA PCR. Neuronal c-srcN2 expression varied significantly in the following order: group 1 > group 2 > group 3. The level of expression of trk A was markedly reduced in group 3 but did not differ in groups 1 and 2. Most tumors in group 3 overexpressed N-myc. However, N-myc expression in group 1 was significantly higher than that in group 2. Thus, the characteristics of proto-oncogene expression in screening-positive tumors included enhanced expression of c-srcN2 and N-myc mRNA, regardless of nonamplification of N-myc. Our results suggest that the role of N-myc differs in neuroblastomas detected by screening and in N-myc-amplified tumors.

Sleep apnea impairs the arousal response to airway occlusion.

We hypothesized that the increased arousal threshold to upper airway occlusion exhibited by patients with obstructive sleep apnea (OSA) is in part secondary to the disease process itself. To test this hypothesis, we studied the effects of withdrawal of three nights of nasal continuous positive airway pressure (CPAP) treatment on arousal in six male patients with severe OSA who were using nasal CPAP on a long-term basis. During the control week, patients slept with nasal CPAP at home and on the first of 2 nights in the sleep laboratory (night C1, CPAP; night C2, no CPAP). During the apnea week, patients slept without nasal CPAP for 2 nights at home and 2 nights in the sleep laboratory (AP1, AP2). The control and apnea weeks were consecutive and in random order. The mean (+/-SEM) apnea+hypopnea index was 76.9 +/- 7.1 on AP1 vs 3.1 +/- 1.0 events per hour on C1 (p<0.05). Thus, the laboratory night (and presumably the 2 nights at home) preceding AP2 had dramatic increases in apnea compared with the nights preceding C2. The apnea duration during nonrapid eye movement sleep on nights following apnea was greater (AP2: 28.7 +/- 1.5 vs C2: 25.5 +/- 1. 7 s; p<0/05) and the arousal threshold as reflected by the maximum esophageal pressure deflection preceding arousal was higher (DPmax) (AP2: 55.1 +/- 5.7 vs C2: 45.3 +/- 6.4 cm H2O; p<0.005). We conclude that prior sleep apnea increases the arousal threshold to upper airway occlusion on subsequent nights and prolongs the apneic events.

Pulsed Doppler sonography for the diagnosis of strangulation in small bowel obstruction.

BACKGROUND/PURPOSE: This study was undertaken to assess the usefulness of pulsed Doppler sonography (PDS) for the detection of strangulation in small bowel obstruction by evaluating the hemodynamics in the superior mesenteric artery (SMA). METHODS: The authors performed PDS in 117 normal children: 22 children aged 0 to 1 months (group I), 27 children aged 1 to 12 months (group II), 36 children aged 1 to 6 years (group III), and 32 children aged 7 to 15 years (group IV). Patients included 25 with simple obstruction: 1 in group II, 10 in group III, and 14 in group IV; and 9 with strangulating obstruction: 2 in group I, 2 in group II, 3 in group III, and 2 in group IV. The authors measured the peak-systolic velocity, end-diastolic velocity (EDV), and mean average velocity and calculated the resistive index (RI). RESULTS: The authors observed both a significant decrease in the EDV and increase in the RI for the SMA in strangulating obstruction compared with simple obstruction. CONCLUSION: Analysis of the hemodynamics in the SMA using PDS is useful to differentiate strangulating obstruction from simple obstruction.

Pulsed Doppler sonography of the hilar renal artery: differentiation of obstructive from nonobstructive hydronephrosis in children.

BACKGROUND/PURPOSE: It is difficult to detect the arcuate or cortical renal arteries when performing pulsed Doppler sonography (PDS) for congenital hydronephrosis. This study was undergone to assess the usefulness of PDS of the hilar renal artery to differentiate obstructive from nonobstructive hydronephrosis. METHODS: The authors performed PDS of the hilar renal artery in 80 normal children: 20 aged 0 to 1 months (group I), 20 aged 1 to 12 months (group II), 20 aged 1 to 6 years (group III), and 20 aged 7 to 15 years (group IV). Based on diuretic renography findings, 22 kidneys from 19 children with a ureteropelvic junction (UPJ) stricture were divided into 7 dilated obstructed and 15 dilated nonobstructed kidneys. The peak-systolic velocity (PSV), end-diastolic velocity (EDV), mean average velocity (Vm) and the resistive index (RI = [PSV - EDV]/PSV) were measured at the hilar renal artery. RESULTS: There was a significant difference in the RI of the hilar renal artery between obstructive and nonobstructive hydronephrosis. CONCLUSION: A pulsed Doppler evaluation of the hilar renal artery is useful for detecting an obstructive UPJ stricture compared with assessing arcuate or cortical renal arteries.

Nonoperative management of blunt pancreatic injury in childhood.

PURPOSE: Nonoperative management for blunt pancreatic injury in children was performed between 1977 and 1998. The efficiency and safety of nonoperative management was examined. METHODS: Pancreatic injury was diagnosed in 20 children. The surgical indication was determined by hemodynamic instability and the management of associated injuries. Children without surgical indications were treated initially by nonoperative management. RESULTS: Nineteen of 20 children were treated initially nonoperatively, and 18 of the 19 survived. Surgical exploration was performed in only 1 child with perforation of the duodenum and bile duct. One child died of complications of total parenteral nutrition. Ultrasound scan and computed tomography scan showed pancreatic contusion in 9, laceration in 6, and injury of the main pancreatic duct (MPD) in 5. Pseudocysts were detected in 10 (5 laceration and 5 MPD injury). Pseudocysts smaller than 10 cm disappeared after nonoperative management, and those larger than 10 cm required operative management. Rupture of pseudocysts occurred in 2 children by rotating the upper torso. CONCLUSIONS: Nonoperative management of pancreatic injuries is effective in children, although careful management is required to avoid complications. Pseudocysts smaller than 10 cm were treated successfully by nonoperative management, and those larger than 10 cm required surgical management.

Hyperbaric oxygenation therapy for simple adhesive postoperative intestinal obstruction in children: comparison of the use of a short tube versus a long tube.

We hypothesized that hyperbaric oxygenation (HBO) combined with a long tube (LT) [HBO + LT] would be more effective than HBO combined with a short tube (ST) [HBO + ST] for simple adhesive postoperative intestinal obstruction (APIO) in children, assuming that there is synergism between HBO and LT. The objective of this study was to determine retrospectively the effect of HBO + LT compared to HBO + ST for simple APIO in children. Seventy-three patients were diagnosed with simple APIO, and 51 of these patients were treated with HBO + LT during 104 HBO sessions, while 22 were treated with HBO + ST during 34 HBO sessions. HBO was performed at a pressure of 2 atmospheres for 60 minutes once daily. The recovery rates after HBO therapy were 87.5 % for the HBO + LT group and 82.4 % for the HBO + ST group (p = 0.4496). HBO was performed 5 +/- 3 (range 1 to 15) times for the HBO + LT group and 4 +/- 2 (range 1 to 8) times for the HBO + ST group (p = 0.9847) for ultimate recovery from simple APIO. The recovery rate after HBO therapy of up to 6 sessions was 78.2 % for HBO + LT and 92.1 % for HBO + ST (p = 0.0360) among the cases that recovered ultimately. The effect of HBO + LT did not significantly differ from that of HBO + ST, but the insertion of an LT is more intricate and the cost is higher than that of an ST. Therefore, we conclude that the use of an LT is not necessarily required for HBO therapy for simple APIO.

Serological detection of antibodies against Paracoccidioides brasiliensis in dogs with leishmaniasis.

The aim of this study was to detect antibodies against Paracoccidioides brasiliensis in dogs seropositive and seronegative for leishmaniasis. Sera from 836 dogs (449 positive and 387 negative to leishmaniasis) were analysed by ELISA and the immunodiffusion test using gp43 and exoantigen, respectively. The analysis of the 836 serum samples by ELISA and the immunodiffusion test showed a positivity of 67.8 % and 7.3%, respectively, for P. brasiliensis infection. The dogs positive to leishmaniasis showed a higher reactivity to gp43 (79.9%) and exoantigen (12.7%) than the negative ones (54.0% and 1.0%, respectively). The higher reactivity to P. brasiliensis antigens may be due to cross-reactivity or a co-infection of dogs by Leishmania and P. brasiliensis. The lower correlation (0.187) observed between reactivity to gp43 and Leishmania antigen reinforces the latter hypothesis.

Incorporation of microinjected biotin-labelled actin into nascent myofibrils of cardiac myocytes: an immunoelectron microscopic study.

Incorporation of microinjected biotin-labelled actin into nascent myofibrils of cultured cardiac muscle cells was investigated by immunogold electron microscopy. At the proximal parts of myofibrils, gold labelling was first found (at about 4 min after injection) around the A-band level. This observation suggests that polymerization of actin or the addition of newly-formed actin filaments occurs preferentially in association with myosin filaments to increase the myofibrillar girth. The distal terminals of developing myofibrils were also labelled at about 4 min after injection. This rapid incorporation of actin subunits at the myofibrillar ends suggests the continued reorganization and/or de novo formation of myofibrils at these positions. Along the extending direction of the myofibrillar terminals, gold particles were arranged in rows on the inner surface of the sarcolemma. These rows of particles continued to become longer with incubation. It appears that actin subunits are added at the membrane-associated ends of pre-existing actin filaments to increase the length of myofibrils.

Dynamics of actin and assembly of connectin (titin) during myofibrillogenesis in embryonic chick cardiac muscle cells in vitro.

Immunogold electron microscopy of cardiac myocytes microinjected with biotin-labeled actin showed that gold labeling was first found around the A band level of myofibrils at their proximal parts. This observation suggests that polymerization of actin and/or the addition of newly formed actin filaments occurs preferentially in association with myosin filaments to increase the myofibrillar girth. At the distal portions of developing myofibrils, their terminal ends were initially labeled, suggesting that continued reorganization and/or de novo formation of myofibrils occurs at these locations. Soon, gold particles were seen along the termini of growing myofibrils. This appears to indicate that actin subunits are added at the membrane-associated ends of preexisting actin filaments to increase the length of myofibrils. Adhesion plaque proteins, e.g., vinculin, do not appear to play any role in assembling actin monomers at these sites on the inner surface of the sarcolemma. Immunofluorescence and immunoelectron microscopy of cardiomyocytes double-stained with antibodies against two distant domains of connectin (titin) filaments and other sarcomeric proteins showed that these domains of connectin filaments and myosin were synthesized almost simultaneously on large polyribosomes and/or associated immediately after the synthesis of these molecules. Connectin and myosin bands were formed after alpha-actinin striations (Z bands) were seen on preformed I-Z-I-like structures.(ABSTRACT TRUNCATED AT 250 WORDS)

Triazolam in patients with obstructive sleep apnea.

The purpose of this study was to assess the effect of triazolam (0.25 mg) on apnea duration and the arousal response to airway occlusion during sleep in patients with severe obstructive sleep apnea (OSA). Twelve male subjects with a mean (+/- SD) age of 46.6 +/- 14.1 yr and body weight of 260.8 +/- 55.9 lb were studied on two nights separated by a nonstudy night. They ingested triazolam (0.25 mg) or placebo 0.5 h before bedtime in a randomized double-blind crossover manner. In non-rapid-eye-movement (NREM) sleep, the mean (+/- SEM) duration of apnea/hypopnea was slightly increased (26.8 +/- 1.7 versus 23.8 +/- 1.2 s, p < 0.02) and the mean nadir in arterial oxygen saturation lower (80.1 +/- 1.9 versus 84.2 +/- 1.4%, p < 0.001) on triazolam nights. In NREM sleep, the deflections in esophageal pressure prior to apnea termination were higher on triazolam nights (53.3 +/- 5.4 versus 44.5 +/- 4.8 cm H2O, p < 0.001). However, the rate of increase in inspiratory effort (esophageal pressure deflections) during obstructive events was not decreased by triazolam. We conclude that triazolam increases the arousal threshold to airway occlusion, but that this results in only modest prolongation of event duration and increased desaturation at a dose of 0.25 mg in a group of large sleep apnea patients.

Effect of upper airway anesthesia on obstructive sleep apnea.

We hypothesized that upper airway mechanoreceptors contribute to the arousal stimulus that occurs with upper airway occlusion in obstructive sleep apnea (OSA). If so, upper airway anesthesia (UAA) should reduce the arousal stimulus and impair the arousal response. To test this hypothesis, we studied the effects of UAA on apnea duration and the esophageal pressure deflection before arousal in a group of patients with severe OSA. On two study nights separated by one week, subjects were monitored for 2 h after lights out. They were then awakened and either 5 cc of 4% lidocaine or saline (random order) was dripped into the upper airway via the nose over 10 min. Another 2 h of monitoring was then performed. Variables on the first and second parts of the control (C1 and C2) and lidocaine nights (L1 and L2) were compared during non-rapid eye movement sleep using the analysis of variance. With lidocaine, the mean (+/- SEM) apnea duration increased from 24.2 +/- 2.6 (L1) to 30.7 +/- 2.3 (L2) s but with saline the apnea length was unchanged from 23.3 +/- 1.5 (C1) to 23.4 +/- 1.6 (C2) (L2 > [L1, C1, C2], p < 0.01). In addition, the maximum esophageal pressure deflection (cm H2O) before arousal increased after lidocaine from 63.6 +/- 14.5 (L1) to 84.1 +/- 14.7 (L2) but after saline was unchanged from 62.1 +/- 15.4 (C1) to 60.0 +/- 15.2 (C2), (L2 > [L1, C1, C2], p < 0.05). We conclude that UAA impairs the arousal response to airway occlusion. This suggests that input from upper airway mechanoreceptors during obstructive events contributes to the total arousal stimulus in patients with OSA.

Strangulated umbilical hernia in a child: report of a case.

Most umbilical hernias in children close spontaneously. Complications associated with umbilical hernias are rarely observed during follow-up. We report herein a 5-month-old girl with a strangulated umbilical hernia. Her umbilicus was hard, reddish, and irreducible. Plain radiography of the abdomen showed signs of mechanical ileus. The patient was thus diagnosed to have a strangulated umbilical hernia. A 5-cm section of the ascending colon and a 5-cm section of the terminal ileum, as well as the cecum and appendix, were congested, edematous, and erythematous, and together were enclosed by a firm hernial ring. A closure of the fascial defect and umbilicoplasty were performed. The postoperative course was uneventful. In patients with infantile umbilical hernias, strangulation may occur as the fascial defect decreases in size.

Upper airway anesthesia reduces phasic genioglossus activity during sleep apnea.

We hypothesize that stimulation of upper-airway mechanoreceptors during obstructive apnea augments upper airway muscle activity. If so, upper-airway anesthesia (UAA) should reduce mechanoreceptor output and therefore upper-airway muscle activity. To test this hypothesis, we studied the effect of UAA on the relationship between the phasic activity of the moving-time average (MTA) of the genioglossus electromyogram (EMG-GG) and the esophageal pressure deflection (DP) during obstructive apneas in non-rapid-eye-movement (NREM) sleep in a group of six men with severe sleep apnea. Before UAA, the phasic EMG-GG was linearly related to the deflections in esophageal pressure (DP) during the last three occluded breaths (both progressively increased). After UAA, the mean ratio of EMG-GG to DP decreased to 23% of the control value, from 0.17 +/- 0.04 to 0.04 +/- 0.01 (mean +/- SEM) arbitrary units/cm H2O (p < 0.05). The mean slope of the EMG-GG-versus-DP regression lines also decreased to 23% of the control value, from 0.22 +/- 0.03 to 0.05 +/- 0.01 arbitrary units/ cm H2O (p < 0.01). These findings suggest that stimulation of upper-airway mechanoreceptors during obstructive apnea in NREM sleep augments phasic genioglossus activity.

[A morphological study of the cranial base and dentofacial structure of Japanese with Angle Class II, div. 1 malocclusion--as compared with American white with Angle Class II, div. 1 malocclusion].

The purpose of this study was to clarify the morphological differences of Angle class II, div. 1 malocclusion between Japanese and American Caucasians by comparing their cranial base and dentofacial morphology. Materials were lateral cephalograms of 61 Japanese (30 males: mean age 12y3m and 31 females: mean age 12y10m) and 67 American Caucasians (27 males: mean age 13y6m and 40 females: mean age 13y) with Angle class II, div. 1 permanent dentition. Results were as follows: 1. The anterior cranial base length in Japanese with Angle class II, div. 1 malocclusion was significantly shorter than that of American Caucasians. 2. The maxillary length in Japanese with Angle class II, div. 1 malocclusion was significantly shorter than that of American Caucasians. 3. Less than SNA, less than SNB and less than ANB showed no significant difference between Japanese and American Caucasians with Angle class II, div. 1 malocclusion. 4. The whole mandibular length in Angle class II, div. 1 malocclusion of Japanese males and American males showed no significant difference. But the mandibular body length of Angle class II, div. 1 malocclusion in Japanese females was significantly shorter than that of American ones. 5. No significant difference was observed in gonial angle when the two groups were studied. 6. As compared with American Caucasians, the backward rotation of the mandible was evidently observed in Japanese with Angle class II, div. 1 malocclusion.

Management of blunt hepatic injury in children: usefulness of emergency transcatheter arterial embolization.

We reviewed our experience to determine the usefulness of emergency transcatheter arterial embolization (TAE) for severe blunt hepatic injury (BHI) in children. Between 1978 and 2000, 21 children with BHI (14 boys and 7 girls, ranging in age from 2 to 14 years) were managed according to our protocol. The patients who were hemodynamically stable, and had no other associated injury requiring laparotomy, regardless of the hepatic injury grade, were managed nonsurgically. Emergency angiography and TAE performed after a CT scan revealed extravasation of the contrast medium. Of the 21 patients, 3 underwent emergency laparotomy; 2 due to hemodynamic instability despite fluid resuscitation (1 died), and the 3rd patient because of associated injury. The other 18 patients (86%) were initially managed nonsurgically; however, 2 underwent delayed laparotomy because of complications (1 each of suspected delayed hepatic hemorrhage and liver abscess). Nonsurgical management was completed in the remaining 16 (89%) with no morbidity and mortality. Two of the 16 returned to a hemodynamically stable condition with fluid resuscitation, but were compromised with persistent hepatic hemorrhage, and were successfully treated with emergency TAE. We propose that emergency TAE should be considered as an initial treatment for severe BHI in children.

Multicystic dysplastic kidney detected by prenatal ultrasonography: natural history and conservative management.

Conservative management of multicystic dysplastic kidney (MCDK) without nephrectomy has recently been advocated. The purpose of this study was to determine the clinical course of conservatively managed unilateral MCDK detected prenatally. Between 1991 and 2001, ten children (three boys and seven girls) with unilateral MCDK detected by prenatal ultrasonography (US) were prospectively followed at our institution. At birth, US confirmed the prenatal findings in all cases. All patients underwent voiding cystourethrography, intravenous pyelography, and radionuclide scans. Postnatal follow-up US examinations were performed every 3 months until patients were 5 years old and annually from then forward. The mean age at diagnosis during the prenatal period was 29 weeks of gestation (range 21-38 weeks). Median follow-up time was 42 months (range 17-125 months). Follow-up US was performed in eight children; three (38%) showed partial resolution, three (38%) complete resolution, and two (24%) no change in cyst size. The mean age at complete resolution of the lesion was 23 months (range 9-33 months). No children developed hypertension or tumors, and all maintained normal growth. In the present study, the natural history of MCDK was benign, and serial US monitoring showed that the affected kidneys frequently showed resolution with time. The results of this study support the conclusion that a nonsurgical approach for patients with MCDK is advisable.

Successful surgical treatment of two cases of congenital chylous ascites.

The authors report on 2 patients with congenital chylous ascites who underwent successful lymphatic duct ligation after a laparoscopic lymphoid dye test. Fetal ascites had been detected in both cases, and both babies were born with marked abdominal swelling. Given that conservative treatment by medium-chain triglyceride (MCT) milk and total parenteral nutrition (TPN) was ineffective, the authors elected to perform lymphatic duct ligation on the 95th postnatal day in the former case and on the 27th postnatal day in the latter case. Lipophilic dye was administered preoperatively both through oral and subcutaneous routes, and the peritoneal cavity was explored using laparoscopy. This laparoscopic lymphoid dye test precisely identified the area of chylous leakage, and the authors were able to repair the malformed lymphatic duct directly at laparotomy. Both postoperative courses have been favorable with no recurrence of symptoms. The lymphatic duct ligation should be considered in cases resistant to conservative treatment for over a month. The present laparoscopic lymphoid dye test is a novel and useful procedure that allows surgeons to identify the exact location of chylous leakage, and thus successfully ligate the lymphatic duct.

Intralobar bronchopulmonary sequestration evaluated by contrast-enhanced three-dimensional MR angiography.

Bronchopulmonary sequestration (PS) is characterized by non-functioning lung tissue fed from one or several aberrant systemic arteries. The condition is diagnosed by visualizing the feeding arteries using non-invasive CT, MRI, colour Doppler sonography or conventional angiography. We present a 5-year-old boy in whom intralobar sequestration was diagnosed using contrast-enhanced 3D MR angiography, which visualised fine blood vessels in the thoraco-abdominal region without arterial puncture. This technique is useful for diagnosing PS.

Expression of MRP and cMOAT in childhood neuroblastomas and malignant liver tumors and its relevance to clinical behavior.

Advanced neuroblastoma and malignant liver tumor are representative childhood cancers for which combined chemotherapy including cisplatin and doxorubicin is routinely performed. The prognosis of patients with tumors which develop multiple drug resistance (MDR) is unfavorable. To elucidate the role of multidrug resistance-associated protein (MRP) and canalicular multispecific organic anion transporter (cMOAT) in the clinical behavior of the tumors, we examined 42 neuroblastomas and 10 malignant liver tumors for the expressions of MRP and cMOAT by quantitative RNA-polymerase chain reaction (PCR). The amplification and expression of N-myc oncogene in the neuroblastomas were also investigated. We found a close association between MRP and N-myc expression in each neuroblastoma sample but no significant relationship between MRP expression and the patients' outcome. The forced expression of N-myc failed to enhance the expression of MRP in N-myc transfected neuroblastoma cell lines. cMOAT was rarely expressed in the neuroblastomas, but was frequently expressed in the malignant liver tumors. The expression of MRP and cMOAT in the childhood liver tumors was more common and higher, especially in advanced cases with a poor outcome, than that observed in normal liver or in 9 hepatocellular carcinomas from adult patients. The enhanced expression of these genes might be characteristic of childhood malignant liver tumors and related to their clinical chemoresistance.