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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric surgery international 11 (1996), S. 261-265 
    ISSN: 1437-9813
    Keywords: Testicle ; Maldescent ; Nitrofen ; Germ cell ; Sertoli cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the rat model of nitrofen-induced congenital diaphragmatic hernia, we found the testicles in a high abdominal position in many male animals, and undertook to investigate whether the teratogen interferes with testicular descent and development. Male fetuses from time-mated Wistar rats treated intragastrically with 100 mg nitrofen dissolved in oil on day 9.5 of gestation were compared with control fetuses from mothers receiving only vehicle. The litters were recovered by cesarean section on days 17, 19, and 21 of gestation; the position of the testicles in male animals was recorded, and their volume was measured prior to histological assessment of mean tubular diameter, number of germ cells per tubule, and degree of collagenization of the tunica albuginea. Testicular maldescent was present in 100% of nitrofen-exposed fetuses on the 17th gestational day, 77% of those recovered on day 19, and 41% of those near term (21st day), whereas all control animals but 1 had “descended” gonads on all three days. Testicular volume was significantly decreased in treated fetuses on the 21st gestational day, and the mean tubular diameter was significantly decreased in all three age groups. Experimental and control animals had similar numbers of germ cells per tubule. The albuginea layer had apparently normal collagen content in all groups. These findings suggest that prenatal exposure to nitrofen interferes with both transabdominal descent of the testicle (transinguinal descent is postnatal in the rodent) and its normal development. Previous evidence and the present results authorize speculation on the possible role of nitrofen-induced prenatal thyroid hypofunction in the pathogenesis of maldescent and maldevelopment in this model, since thyroid hormones act directly on Sertoli cells, which secrete müllerian inhibiting substance, which is likely responsible for transabdominal descent.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1437-9813
    Keywords: Esophageal atresia ; Tracheoesophageal fistula ; Esophagus ; Rats ; Adriamycin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We recently reported on a new fetal rat model of esophageal atresia (EA) with tracheoesophageal fistula (TEF) induced by prenatal exposure to adriamycin (1.75 mg/kg i. p. injected daily to the pregnant dam from the 6th to 9th gestational days). With this treatment regime, many fetuses were resorbed and the number of associated malformations was very high. The present study demonstrates that similar doses of the drug administered only on the 8th and 9th gestational days allow higher fetal survival (9.7 ∓ 3.9 vs. 6.8 ∓ 4.7 fetuses per litter, P 〈 0.01) with a similar incidence of EA-TEF (41.2% vs. 56.4%, n. s.) and decreased occurence of associated anorectal and genitourinary malformations. Since this model is an instrument for further investigation of the disturbed cellular and morphogenetic events leading to EA and TEF, the narrowing of the embryologic window obtained by the present study will allow better focusing of the research on the critical period of time involved.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric surgery international 13 (1998), S. 307-307 
    ISSN: 1437-9813
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric surgery international 15 (1999), S. 201-205 
    ISSN: 1437-9813
    Keywords: Key words Esophagus ; Atresia ; Notochord ; Adriamycin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Esophageal atresia (EA) is often accompanied by vertebral defects and other anomalies. The adriamycin rat model of EA has disclosed the embryology of the malformation and shown that the vertebrae and notochord are also abnormal. This study describes the nature of notochord malformations in rat embryos exposed to adriamycin. Time-mated rats received either 1.75 mg/kg adriamycin or vehicle i.p. on gestational days (E) 6 to 9; E-12, E-12.5, and E-13 embryos were harvested, embedded in paraffin, and serially sectioned at 3 μm in transverse plane from the head to the stomach for subsequent PAS staining. The findings in both groups were compared at the three endpoints. Control embryos had neither tracheoesophageal nor notochord malformations. On day 12, only 11/36 adriamycin embryos were normal; 7/36 had abnormal notochords, 11/36 had EA, and 7/36 had both. The corresponding figures for 12.5 days were 12/27, 0/27, 7/27, and 8/27 and those for the day 13 7/23, 5/23, 3/23, and 8/23. The malformed notochords were thickened, bifurcated, or trifurcated in the sagittal plane. The simultaneous presence of notochord and esophageal malformations suggests a direct link between both defects, but our observation of isolated occurrence of both shows that they reflect two expressions of the profound disturbance of embryonic para-axial organization responsible for the cluster of malformations rather than a cause-effect association.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric surgery international 8 (1993), S. 389-394 
    ISSN: 1437-9813
    Keywords: Barrett's oesophagus ; Gastro-oesophageal reflux ; Acid exposure ; Alkaline exposure ; Helicobacter pylori
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This paper describes 12 cases of Barrett's oesophagus (BE) selected out of a population of 364 refluxing children studied by X-ray, manometric, pH-metric, endoscopic, and bioptic methods in one single institution from 1986 to 1990. Their mean age was 14 years, the male-female ratio was 5:7, and all had had gastro-oesophageal reflux (GER) symptoms since infancy. At the time of diagnosis 9 (75 %) had vomiting, 6 (50 %) respiratory tract disease, 3 (25 %) hæmorrhage, and 1 (8 %) peptic stenosis. Seven were cared for in special institutions for brain-damaged patients and 2 had been operated upon for oesophageal atresia at birth. Lower oesophageal sphincter pressure was very low in 8 out of 9 children studied and propulsive peristalsis was markedly decreased. Excessive acid exposure was documented in 8 out of 10 patients studied and simultaneous gastric and oesophageal pH-monitoring demonstrated massive duodeno-gastric alkaline reflux in 3 (2 of them with “normal” oesophageal pH studies). Histological and histochemical studies, including special mucin staining revealed that the columnar-lined epithelium was of the fundic type in 2 cases, the junctional type in 7, and the specialised type in the remaining 3. Helicobacter pylori was found in the mucosa of 8 patients (in massive amounts in 3). All patients had a Nissen fundoplication with good results in terms of disappearance of the GER symptoms. The present series confirms that BE should be looked for endoscopically in children with GER and supports the hypothesis that long duration of GER and excessive acid-alkaline chemical exposure of the oesophageal lining contribute to the pathogenesis of mucosal changes. The role of H. pylori is not clear, but its intriguing presence in the majority of our cases indicates that further research along these lines is warranted.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1437-9813
    Keywords: Congenital diaphragmatic hernia ; Predictor factors ; Extracorporeal membrane oxygenation (ECMO) ; Oxygenation index ; Ventilatory index
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Some newborns with congenital diaphragmatic hernia (CDH) and severe pulmonary hypertension cannot be saved by conventional treatment and may obtain some benefit from extracorporeal membrane oxygenation (ECMO) as a bridging measure until adequate hematosis is possible. Early prediction of the insufficiency of “optimal” assistance is still unclear; we reviewed our recent experience with CDH patients in an attempt to evaluate the real need for ECMO in our institution. Between 1987 and 1994, 47 newborns with CDH manifested in the first 24 h were treated with maximal ventilatory assistance (including high-frequency ventilation in 12 cases) and vasoactive drugs prior to surgical repair. In order to summarize the ventilatory and blood-gas parameters, we determined oxygenation index (OI) and ventilatory index (VI) and compared the results in survivors and nonsurvivors. Overall survival was 60% (2 cases of Fryns' syndrome were excluded from analysis). OI was 10.3±5.7 (mean ± SD) for survivors and 46.2 ± 37.8 for nonsurvivors (P 〈 0.01). VI was 460.9±303 and 1,532±500.6, respectively (P 〈0.01). Bayesian analysis and receiver operating characteristic curves enabled us to select a threshold value of OI of 20 as the best means of predicting survival in our current conditions (sensitivity: 0.7, specificity: 0.83). The generally accepted figure of 40 had a sensitivity of 1 but a specificity of only 0.44. For VI, the best threshold value was 1,100 (sensitivity: 0.93, specificity: 0.94), whereas the generally used figure of 1,000 had 0.89 and 1, respectively. According to our results, with our current management conditions, approximately 50% of our CDH patients might have obtained some benefit from ECMO.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1437-9813
    Keywords: Key words Adriamycin ; Apoptosis ; Embryogenesis ; Esophageal atresia ; Notochord ; VATER association
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The adriamycin-induced rat model of the VATER association has provided a means of studying the morphogenesis of a variety of major congenital structural abnormalities similar to those seen in humans with the VATER association. Most interest has been centered on the foregut, where the model has clarified some aspects of the development of esophageal atresia (EA), tracheal agenesis, and other communicating bronchopulmonary foregut malformations. It has demonstrated aberrations in the nerve supply to the esophagus in EA and allowed the study of tracheomalacia. A relationship between an abnormal notochord, foregut abnormalities, and vertebral defects has been shown, and the model has reignited interest in the role of the notochord as a regional organizer of axial development. The normal temporospatial characteristics of apoptosis during fore- and hindgut development is disturbed in this model, resulting in abnormal morphology. The indications are that this model will continue to clarify the processes that lead to many of the structural congenital abnormalities that are seen in infants born with the VATER association.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1437-9813
    Keywords: Pediatric liver transplantation ; Hepatic artery thrombosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thrombosis of the hepatic artery (HAT) is a severe complication of liver transplantation, and most cases need regrafting. The aim of this study was to review our experience with this complication. From January 1986 through January 1992, 76 liver transplants were performed in 59 pediatric patients at the Children's Hospital “La Paz”, Madrid. The diagnosis of HAT was made in 12 cases (15.7%). The common patterns of clinical presentation were: fulminant liver necrosis (5), bile leak due to necrosis of the bile duct (4), and relapsing bacteremia (3). Clinical symptoms of fulminant liver necrosis started within the first 2 weeks after transplantation, with rapid deterioration and steep rises in SGOT and SGPT levels. All these patients were retransplanted on an urgent basis, but only 1 is alive 4 years later. Four patients developed bile leaks 13 to 60 days after transplantation; SGOT, SGPT, and total bilirubin were only slightly increased. Three children were retransplanted electively and are alive with a mean follow-up of 3 years. One exceptional patient had a Roux-en-Y jejunostomy and is doing well 30 months later with his original graft. The 3 remaining children had episodes of septicemia with hepatic abscess, liver infarction, and pleural effusion. Liver function tests were normal, with bilirubin levels below 2 mg/dl. All patients were retransplanted, but only 1 is alive and well 13 months later. In the present series, we found that early HAT produces fulminant clinical deterioration requiring an urgent regraft. Late HAT presenting with either infection or bile leak allows time for treatment by elective retransplantation. The best survival was obtained in the latter group.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric surgery international 3 (1988), S. 195-197 
    ISSN: 1437-9813
    Keywords: Prenatal diagnosis ; Neuroblastoma ; Adrenal tumor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A right retroperitoneal mass with mixed solid and cystic pattern was detected sonographically in a fetus in the 36th week of pregnancy. After term delivery radiologic, sonographic, and CT studies confirmed the presence of a spherical, 5 × 4-cm mass above the right kidney with mixed echogenicity. At operation an enlarged adrenal gland containing hemorrhagic spaces was removed. Histological studies revealed adrenal neuroblastoma. This prenatal sonographic pattern was suggestive of neuroblastoma because it was identical to that of the only similar case reported so far. Prenatal detection is therefore possible and should be regarded as desirable since early diagnosis and treatment provide the best chances for cure.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric surgery international 15 (1999), S. 184-187 
    ISSN: 1437-9813
    Keywords: Key words Congenital diaphragmatic hernia ; Associated malformations ; Nitrofen ; Tracheobronchial anomalies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neonates with congenital diaphragmatic hernia (CDH) have other malformations that contribute to the high mortality. The nitrofen rat model allows experimental study of these anomalies. This study examines whether the tracheobronchial tree is also abnormal in this model. Time-mated rats received 100 mg nitrofen on gestational day 9.5; 90 fetuses were harvested on day 21 (near full term) and dissected. The trachea and bronchi were stained with alcian blue-alizarin red and their anatomy was examined by transillumination under a microscope. The findings were compared with those of 11 suitable controls. Control pups had no malformations. Those with CDH (n = 57) had significantly decreased numbers of tracheal rings in comparison with controls (22.9 ± 1.9 vs 26 ± 1.9, P 〈 0.05) and 40/57 had fragmented rings (0 in controls). Twelve CDH animals had, in addition, tracheal stenoses of variable severity, sometimes related to vascular rings. Nitrofen fetuses without CDH (n = 33) had only short tracheas and 4 had mild stenoses. Nitrofen-exposed fetuses have, in addition to lung hypoplasia and sometimes CDH, severe tracheobronchial anomalies that suggest the involvement of pathogenetic mechansims capable of acting on various tissue components. The genetic control of organogenesis is most probably disturbed by the teratogen.
    Type of Medium: Electronic Resource
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