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Prions are highly resistant to the decontamination procedures normally used to inactivate conventional pathogens. This is a challenging problem not only in the medical and veterinary fields for minimizing the risk of transmission from potentially infective sources but also for ensuring the safe disposal or subsequent use of animal by-products. Specific pressure autoclaving protocols were developed for this purpose, but different strains of prions have been reported to have differing resistance patterns to established prion decontamination procedures, and as additional TSE strains are identified it is necessary to determine the effectiveness of such procedures. In this study we assessed the efficacy of sterilization using the EU recommended autoclave procedure for prions (133°C, 3 Bar for 20 min) on the atypical or Nor98 (AS/Nor98) scrapie strain of sheep and goats. Using a highly sensitive murine mouse model (tg338) that overexpresses ovine PrP C , we determined that this method of decontamination reduced the infectivity titre by 10 10 . Infectivity was nonetheless still detected after applying the recommended autoclaving protocol. This shows that AS/Nor98 can survive the designated legislative decontamination conditions, albeit with a significant decrease in titre. The infectivity of a classical scrapie isolate subjected to the same decontamination conditions was reduced by 10 6 suggesting that the AS/Nor98 isolate is less sensitive to decontamination than the classical scrapie source., (© 2019 Blackwell Verlag GmbH.)

Introduction: Scrapie and bovine spongiform encephalopathy (BSE) are transmissible spongiform encephalopathies (TSEs) which naturally affect small and large ruminants respectively. However, small ruminants, which are susceptible to BSE under experimental conditions, have been exposed to the same or similar contaminated food additives as cattle. To date two natural cases of BSE in small ruminants have been reported. As a result surveillance projects, combined with appropriate control measures, have been established throughout the European Union (EU) to minimize the overall incidence of small ruminant TSEs. Although BSE can be differentiated from classical scrapie (subsequently referred to as scrapie) if appropriate discriminatory tests are applied, the value of these tests in BSE/scrapie co-infection scenarios has not been evaluated fully. Mouse bioassay is regarded as the gold standard regarding differentiation of distinct TSE strains and has been used as to resolve TSE cases were laboratory tests produced equivocal results. However, the ability of this method to discriminate TSE strains when they co-exist has not been examined systematically. To address this issue we prepared in vitro mixtures of ovine BSE and scrapie and used them to challenge RIII, C57BL/6 and VM mice., Results: Disease phenotype analysis in all three mouse lines indicated that most phenotypic parameters (attack rates, incubation periods, lesion profiles and Western blots) were compatible with scrapie phenotypes as were immunohistochemistry (IHC) data from RIII and C57BL/6 mice. However, in VM mice that were challenged with BSE/scrapie mixtures a single BSE-associated IHC feature was identified, indicating the existence of BSE in animals where the scrapie phenotype was dominant., Conclusions: We conclude that wild type mouse bioassay is of limited value in detecting BSE in the presence of scrapie particularly if the latter is in relative excess.

Several transgenic mouse models have been developed which facilitate the transmission of chronic wasting disease (CWD) of cervids and allow prion strain discrimination. The present study was designed to assess the susceptibility of the prototypic mouse line, Tg(CerPrP)1536(+/-), to bovine spongiform encephalopathy (BSE) prions, which have the ability to overcome species barriers. Tg(CerPrP)1536(+/-) mice challenged with red deer-adapted BSE resulted in 90% to 100% attack rates, and BSE from cattle failed to transmit, indicating agent adaptation in the deer.

Two cases of unusual transmissible spongiform encephalopathy (TSE) were diagnosed on the same farm in ARQ/ARQ PrP sheep showing attributes of both bovine spongiform encephalopathy (BSE) and scrapie. These cases, UK-1 and UK-2, were investigated further by transmissions to wild-type and ovine transgenic mice. Lesion profiles (LP) on primary isolation and subpassage, incubation period (IP) of disease, PrP(Sc) immunohistochemical (IHC) deposition pattern and Western blot profiles were used to characterize the prions causing disease in these sheep. Results showed that both cases were compatible with scrapie. The presence of BSE was contraindicated by the following: LP on primary isolation in RIII and/or MR (modified RIII) mice; IP and LP after serial passage in wild-type mice; PrP(Sc) deposition pattern in wild-type mice; and IP and Western blot data in transgenic mice. Furthermore, immunohistochemistry (IHC) revealed that each case generated two distinct PrP(Sc) deposition patterns in both wild-type and transgenic mice, suggesting that two scrapie strains coexisted in the ovine hosts. Critically, these data confirmed the original differential IHC categorization that these UK-1 and UK-2 cases were not compatible with BSE., (© 2011 The Authors. Brain Pathology © 2011 International Society of Neuropathology.)

Transmissible spongiform encephalopathies are fatal neurodegenerative diseases that include variant Creutzfeldt-Jakob disease in humans, scrapie in small ruminants, and bovine spongiform encephalopathy (BSE) in cattle. Scrapie is not considered a public health risk, but BSE has been linked to variant Creutzfeldt-Jakob disease. Small ruminants are susceptible to BSE, and in 2005 BSE was identified in a farmed goat in France. We confirm another BSE case in a goat in which scrapie was originally diagnosed and retrospectively identified as suspected BSE. The prion strain in this case was further characterized by mouse bioassay after extraction from formaldehyde-fixed brain tissue embedded in paraffin blocks. Our data show that BSE can infect small ruminants under natural conditions and could be misdiagnosed as scrapie. Surveillance should continue so that another outbreak of this zoonotic transmissible spongiform encephalopathy can be prevented and public health safeguarded.

We present an NMR investigation of the nucleotide-dependent conformational properties of a 44-kDa nucleotide binding domain (NBD) of an Hsp70 protein. Conformational changes driven by ATP binding and hydrolysis in the N-terminal NBD are believed to allosterically regulate substrate affinity in the C-terminal substrate binding domain. Several crystal structures of Hsc70 NBDs in different nucleotide states have, however, not shown significant structural differences. We have previously reported the NMR assignments of the backbone resonances of the NBD of the bacterial Hsp70 homologue Thermus thermophilus DnaK in the ADP-bound state. In this study we show, by assigning the NBD with the ATP/transition state analogue, ADP.AlFx, bound, that it closely mimics the ATP-bound state. Chemical shift difference mapping of the two nucleotide states identified differences in a cluster of residues at the interface between subdomains 1A and 1B. Further analysis of the spectra revealed that the ATP state exhibited a single conformation, whereas the ADP state was in slow conformational exchange between a form similar to the ATP state and another state unique to the ADP-bound form. A model is proposed of the allosteric mechanism based on the nucleotide state altering the balance of a dynamic equilibrium between the open and closed states. The observed chemical shift perturbations were concentrated in an area close to a previously described J-domain binding channel, confirming the importance of that region in the allosteric mechanism.

Background: Vascular rings are uncommon anomalies in which preferred strategies for diagnosis and treatment may vary among institutions. In this report, we offer a description of our approach and a review of our 25-year experience., Methods: A retrospective review was conducted of all pediatric patients with symptomatic tracheoesophageal compression secondary to anomalies of the aortic arch and great vessels diagnosed from 1974 to 2000., Results: Thirty-one patients (38%) of eighty-two patients (mean age, 1.7 years), were identified with double aortic arch, 22 patients (27%) with right arch left ligamentum, and 20 patients (24%) with innominate artery compression. Our diagnostic approach emphasized barium esophagram, along with echocardiography. This regimen was found to be reliable for all cases except those with innominate artery compression for which bronchoscopy was preferred, and except those with pulmonary artery sling for which computed tomography or magnetic resonance imaging, in addition to bronchoscopy, were preferred. Left thoracotomy was the most common operative approach (70 of 82; 85%). Ten patients (12%) had associated heart anomalies, and 6 (7%) patients underwent repair. Complications occurred in 9 (11%) patients and led to death in 3 (4%) patients., Conclusions: In our practice, barium swallow and echocardiography are sufficient in diagnosing and planning the operative strategy in the majority of cases, with notable exceptions. Definitive intraoperative delineation of arch anatomy minimizes the risk of misdiagnosis or inadequate treatment.

Objective: To describe the trends in the pediatric surgeon workforce during the last 25 years and to provide objective data useful for planning graduate medical education requirements., Summary Background Data: In 1975, the Study on U.S. Surgical Services (SOSSUS) was published, including a model to survey staffing. A pediatric surgeon workforce study was initiated in conjunction with SOSSUS as a population, supply, and need-based study. The study has been updated every 5 years using the same study model, with the goals of determining the number and distribution of pediatric surgeons in the United States, the number needed and where, and the number of training programs and trainee output required to fill estimated staffing needs. This is the only such longitudinal workforce analysis of a surgical specialty., Methods: Questionnaires were sent to 100 pediatric surgeons representing the 62 standard metropolitan statistical areas (SMSAs) in the United States with a population of 200,000 or more to verify the names and locations of all active pediatric surgeons and to gain information about the 5-year need for new pediatric surgeons by region. A program was developed to predict the number of pediatric surgeons relative to the total population and the 0-to-17-year-old population in the subsequent 30 years using updated data on the present number and ages of pediatric surgeons, age-specific death and retirement rates, projections of U.S. population by age group, and varying numbers of trainees graduated per year. As each 5-year update was done, previous projections were compared with actual numbers of pediatric surgeons found. The trends during the last 25 years were analyzed and compared and additional information regarding the demographics of practice, trends in reimbursement, and volume and scope of surgery was obtained., Results: The birth rate has been stable since 1994. The 0-to-17-year-old population has been increasing at 0.65% per year; a 0.64% annual rate is projected to 2040. At present, 661 pediatric surgeons are distributed in every SMSA of 200,000 or more population, with an average age of 45 and an average age of retirement 65. The actual number of pediatric surgeons in each 5-year survey has consistently validated previous projections. Trainee output has increased markedly in the past 10 years. The rate of growth of the pediatric surgeon workforce at present is 50% greater than the forecasted rate of increase in the pediatric age group, and during the past 25 years the rate of growth of the pediatric surgeon workforce has been double that of the pediatric population growth. Nationally, significant changes in reimbursement, volume of surgery, and demographics of practice have occurred.

It is well accepted that salicylate ototoxicity results in reversible tinnitus in humans. Salicylate-induced tinnitus may be an example of plasticity of the central auditory system and could potentially serve as a model to further understand mechanisms of tinnitus generation. This study examined levels of glutamic acid decarboxylase (GAD) and the binding characteristics of the GABA(A) receptor in auditory brainstem structures of Long-Evans rats chronically treated with salicylate. Western blotting revealed a significant 63% (P<0.008) elevation of GAD levels in the inferior colliculus (IC) of salicylate-treated subjects. This occurred in subjects demonstrating behavioral evidence of tinnitus. Muscimol saturation analysis was indicative of a salicylate-related increase in receptor affinity. Linear regression of [(3)H]muscimol saturation analysis data revealed a significant (P<0.05) reduction in K(d) values in whole IC (-48%), as well as in the central nucleus of IC (CIC, -58%) and combined external and dorsal cortex of IC (E/DCIC, -46%). The number of GABA(A) binding sites (B(max)) were also significantly (P<0.05) decreased. These changes were observed only in central auditory structures. This suggests that GAD expression and GABA(A) receptor binding characteristics may be altered with chronic exposure to sodium salicylate and these changes may represent aberrant plasticity clinically experienced as tinnitus.

Pharmacological studies of the inferior colliculus (IC) suggest that the inhibitory amino acid neurotransmitter gamma-aminobutyric acid (GABA) plays an important role in shaping responses to simple and complex acoustic stimuli. Several models of auditory dysfunction, including age-related hearing loss, tinnitus, and peripheral deafferentation, suggest an alteration of normal GABA neurotransmission in central auditory pathways. The present study attempts to further characterize noise-induced changes in GABA markers in the IC. Four groups (unexposed control, 0 h post-exposure, 42 h post-exposure, and 30 days post-exposure) of 3-month-old male Fischer 344 rats were exposed to a high intensity sound (12 kHz, 106 dB) for 10 h. Observed hair cell damage was primarily confined to the basal half of the cochlea. There was a significant decrease in glutamic acid decarboxylase (GAD(65)) immunoreactivity in the IC membrane fraction compared to controls (P<0.05) at 0 h (-41%) and 42 h (-28%) post-exposure, with complete recovery by 30 days post-exposure (P>0.98). Observed decreases in cytosolic levels of GAD(65) were not significant. Quantitative muscimol receptor binding revealed a significant increase (+20%) in IC 30 days after sound exposure (P<0.05). These data suggest that changes in GABA neurotransmission occur in the IC of animals exposed to intense sound. Additional studies are needed to determine whether these changes are a result of protective/compensatory mechanisms or merely peripheral differentiation, as well as whether these changes preserve or diminish central auditory system function.

A decline in the ability to discriminate speech from noise due to age-related hearing loss (presbycusis) may reflect impaired auditory information processing within the central nervous system. Presbycusis may result, in part, from functional loss of the inhibitory neurotransmitter GABA. The present study assessed age-related changes of the GABA(A) receptor in the inferior colliculus of young-adult, middle-aged, and aged rats related to: (i) receptor subunit composition and (ii) receptor function. Western blotting was used to measure protein levels of selected GABA(A) receptor subunits in preparations obtained from the inferior colliculus of Fischer 344 and Fischer 344/Brown-Norway F1 hybrid rats. In both strains, the aged group exhibited significant increases in gamma1 subunit protein and a decrease in alpha1 subunit protein. To examine the functional consequence of this putative age-related subunit change, we measured the ability of exogenous GABA to flux/translocate chloride ions into microsac preparations derived from Fischer 344 inferior colliculus. GABA-mediated chloride influx was significantly increased in samples prepared from the inferior colliculus of aged animals. Together with previous studies, these results strongly suggest an age-related change in GABA(A) receptor composition. These changes may reflect a compensatory up-regulation of inhibitory function in the face of significant loss of presynaptic GABA release. These findings provide one example of plastic neurotransmitter receptor changes which can occur during the ageing process.

Gastroesophageal reflux (GER) often develops in children who have undergone prior repair of esophageal atresia/tracheoesophageal fistula (EA/TEF). Fundoplication is necessary in many of these children. The complete wrap (Nissen) fundoplication is often used in this setting. However, poor results have been noted, with a mean failure rate of 30% reported in four recent studies. A partial wrap fundoplication for GER associated with EA/TEF is theoretically attractive, because the poor esophageal motility and diminished acid clearance (already physiologically present) is exacerbated by a complete wrap fundoplication. The authors reviewed their extensive experience with partial wrap (Thal) fundoplication in EA/TEF to determine if the failure rate was better than that reported for the Nissen fundoplication. In the past 18 years, the authors performed 1,467 fundoplication procedures. During the same period, 143 children underwent repair of EA/TEF. Fifty-nine children underwent fundoplication after a previous EA/TEF repair. Most of the fundoplications (58 of 59, 98%) were Thal procedures. Defining failure strictly as a need for reoperation, the failure rate in our series was 15% (9 of 59 children). Compared with the failure rate in the 1,408 non-EA/TEF patients (61 of 1408, 4.3%), results were significantly worse for the EA/TEF group (P > .001). The failure rate of Thal fundoplication performed for GER in the EA/TEF population is substantially higher than the non-EA/TEF patients. The same factors responsible for the development of reflux in these children (poor acid clearance, altered motility, esophageal shortening) may contribute to the higher failure rate. Although partial wrap fundoplication frequently failed (15%), the results were still substantially better than those reported for Nissen fundoplication in these children (30% failure rate).

Unlabelled: Accurate estimations of pediatric surgical manpower needs are necessary if this specialty is to avoid the consequences of under- or oversupply, and reasonable decisions must be made relative to the number of training programs needed., Methods: Fifteen, 10, and 5 years ago, pediatric surgeons (PSs) in 62 standard metropolitan statistical areas (SMSAs) having a population of at least 200,000 were asked to estimate the number of PSs needed in their localities. A computer program analogous to the SOSSUS program was designed to project the number of PSs that would result from various numbers of trainee graduates per year. The program has been updated for comparison. Known input data included the present number and age of PSs, age range of trainees, current US population projections to the year 2025, and the average retirement age., Results: These PSs estimated that 88 additional PSs are needed in the next 10 years. Currently, 26 programs in the United States graduate an average of 24 trainees per year, and six programs in Canada graduate six trainees per year. The previous projection indicated that 20 trainees per year would result in 525 PSs in 1993, and the actual number is 559; so the figures indicate that 27 or 28 PSs are entering practice each year. The apparent increase in numbers is related to entry of Canadian trainees primarily, and a few others, into practice. The current computer projection indicates that 20 graduate trainees per year would result in an absolute increase of 0.55% per year, and 25 per year would result in an increase of 1.43% per year, to 2020, while the increases in the US population would be 1.02% per year for all ages and 0.52% for 0 to 15 year olds. If all programs currently being considered for approval are certified, as many as 36 trainees per year--or 7 times the rate of the 0-15-year population increase--will result., Conclusion: Although an average of 20 graduates per year entering practice would keep pace with the pediatric population, 25 to 27 graduates per year--or 3.5 to 4 times the rate of the 0- to 15-year population increase--can be accommodated now into the current system of delivery of pediatric surgical care on the basis of estimated need. Many more graduates than this would create an excess of surgeons before long.

A persistent left superior vena cava (PLSVC) is the most common anomaly of the major veins. However, an absent right superior vena cava and PLSVC is much less common; fewer than 100 cases have been reported in the world literature in patients with situs solitus. This rare variation was encountered in a newborn requiring extracorporeal membrane oxygenation (ECMO) for meconium aspiration and interfered with venous cannulation. The anomaly was not suspected before an unusual cannula position was observed on the chest radiograph, and it was confirmed by bedside venography. Adequate venous cannulation was obtained through the anomalous vessel using a flexible catheter, allowing for an uneventful ECMO course. The epidemiology and embryology of this incidental anomaly are reviewed, and the methods used to circumvent the difficulties it presented in this case are described.

Intraesophageal pH recordings from 40 patients with abnormal studies who underwent fundoplication during a 1-year period were evaluated. Scores were recalculated for the first 12, 16, and 20 hours, respectively. Five of the recordings were for less than 24 hours, but were grossly abnormal and mathematically could not have normalized at 24 hours. The percentage of studies which were normal at 12, 16, and 20 hours were 20%, 15%, and 0%, respectively. One fifth of the patients would have been denied a fundoplication based on 12-hour results. In addition, 75 consecutive pH recordings were evaluated prospectively. Total scores were determined for the first 12, 16, and 20 hours with accuracies of 85%, 93%, and 92%, respectively. The sensitivity of 12-hour monitoring was only 78%. All abbreviated studies had a low rate of false positives; however, any false positives may be significant when used to determine the need for an operation. Abbreviated studies were associated with high false-negative rates (up to 52% for the 12-hour studies) for the calculated mean duration of sleep reflux, a parameter that has been found to be useful in identifying patients with respiratory symptoms secondary to gastroesophageal reflux. The use of abbreviated pH monitoring is discouraged.

Anterior cricoid resection is an effective procedure to relieve subglottic stenosis. This is well documented in adults, although reports of the procedure in growing airways are limited. Over an 11-year period, seven pediatric patients underwent anterior cricoid resection for recalcitrant subglottic stenosis. In four patients, the stricture was secondary to prolonged intubation, one developed subglottic stenosis following a high placement of tracheostomy for epiglottitis and another had congenital subglottic stenosis. One child had subglottic stenosis combined with laryngotracheoesophageal cleft and more distally located tracheoesophageal fistula. All patients had failed to respond to previous treatment: dilatations (3 to 20), steroid injection (3 patients), and Evan's tracheoplasty (2 patients). All patients had an excellent result from anterior cricoid resection. The median age of children undergoing anterior cricoid resection was 3 years. There was no mortality. Tracheostomy decannulation was accomplished within 12 weeks following operation in all patients. It was necessary to remove a tracheal granuloma in one patient. Anterior cricoid wedge resection leaving the posterior portion of the cricoid in place is done to avoid recurrent nerve injury. It is a relatively simple and effective procedure. There has been minimal morbidity and no mortality. Follow-up from 1 to 11 years shows no recurrence of stenosis. There has been normal laryngeal and airway growth.

Using a posterior repair and rectal suspension procedure for those patients who need surgical treatment of rectal prolapse, we have treated 46 patients over a period of 17 years at Children's Mercy Hospital in Kansas City, MO. One patient with caudal dysgenesis died of multiple congenital anomalies following two unsuccessful attempts at posterior repair and suspension. Four patients developed a recurrence afterwards, which was found to be due to sigmoid intussusception and, presumably, had played a major part in their original prolapse. Two of these required resection, one from the transanal approach and one from the transabdominal approach. One resolved spontaneously and another is as yet unresolved. Three patients had minor mucosal prolapse that was transient and two patients had extrusion of silk sutures but continued to have a very satisfactory result. Overall, 42 patients had satisfactory resolution of their rectal prolapse. Three of the four patients who had unsatisfactory results had associated anomalies that contributed to their poor outcome.

A tumor complex consisting of presacral teratoma and sacral deformity was described along with its occurrence in 6 kindreds. In addition to the tumor and the sacral defect, some patients have had recurrent abscesses, rectal stenosis and skin dimples as manifestation of the tumor. Urinary tract anomalies have also been found to be associated in some patients. The tumor differed considerably from the usual sacrococcygeal teratoma. Only one of the 19 resected tumors had proved to be malignant, although 2 have recurred in a benign manner. This appears to be inherited as a dominant characteristic.

When corrective surgery for tetralogy of Fallot was accomplished through the use of a transannular GORE-TEX patch with a pericardial unicusp, the right-ventricular end-diastolic volumes of all patients studied within a year of the surgery were within the normal ranges because of decreased pulmonary valve regurgitation. The right-ventricular ejection fraction was also only slightly depressed, indicating preservation of right-ventricular function. All patients were noted to maintain normal stroke volumes and normal systolic indices. In contrast, the patients who had transannular patches placed without unicusps showed significantly elevated right-ventricular end-diastolic volumes and lower right-ventricular ejection fractions. These resulted from markedly dilated right-ventricular outflow regions in conjunction with enlarged right-ventricular chambers, which manifested as large dyskinetic areas in the anterior right-ventricular walls.

Radiation injury to arteries can represent a significant complication of therapeutic irradiation, even when the dosage used has not been excessive as judged by approved protocols. Children in whom therapeutic abdominal irradiation has been used should be monitored indefinitely for the development of hypertension. The presence of hypertension in such children with normal blood urea nitrogen (BUN) and creatinine, and without proteinuria, should prompt investigation for a renovascular lesion. Standard bypass procedures are usually effective, although the long-term success may be compromised by continuing changes in affected vessels.

One hundred patients with complications of severe gastroesophageal reflux were treated surgically by the Thal fundoplication. In all patients the symptoms of reflux were eliminated by the operation, although 4 recurred within 8 months. Two of these were due to disruption of the fundoplication and two were due to hiatus hernia not recognized and repaired at initial operation. There were 8 deaths, none related to gastroesophageal reflux or the operation. Four patients required re-operation for intestinal obstruction. The Thal fundoplication is a simple procedure which fixes the distal esophagus within the abdomen and produces an acute angle of His. It is effective in prevention of reflux and the patient is able to burp and vomit if necessary. It has not been associated with dysphagia or "gas bloat" which may follow the Nissen fundoplication.

Ureteropelvic junction (UPJ) obstruction is a common cause of hydronephrosis in infants. Newborns with severe obstruction often have marked improvement following correction; therefore early diagnosis and operation is important. From 1973 to 1983, 21 patients were operated on for UPJ obstruction diagnosed under 6 weeks of age. Six patients (29%) had antenatal ultrasonographic diagnosis. The remaining patients were diagnosed by IVP or radionuclide scan for palpable renal enlargment or for associated anomalies. Seventeen had unilateral and four had bilateral obstruction. Twenty-three pyeloplasties, one primary nephrectomy, and one cutaneous pyelostomy with subsequent nephrectomy were done. All pyeloplasties were dismembered, with tailoring of the renal pelvis. Postoperative renal function was followed with radionuclide scan or IVP. Postoperative complications included a single urinary tract infection in three patients and two bowel obstructions. One early postoperative death occurred in an infant with bilateral obstruction who developed congestive heart failure secondary to severe uncontrollable hypertension. There were two other unrelated late deaths. Documented functional improvement with minimal complications follow unilateral or simultaneous bilateral pyeloplasty in newborns with UPJ obstruction.

Gastroschisis complicated by intestinal atresia is a complex problem. Six cases are presented. A review of the literature and of our own cases shows a high mortality rate. Success or failure is related more to the pathology present than to any specific method of operative management. Resection and primary anastomosis is the favored method of treatment, as the intestine heals well in spite of its appearance. Primary closure of the abdominal wall musculature and skin is done whenever possible. A gastrostomy is used uniformly. Intravenous hyperalimentation is critical to survival of these babies and should be used early. The use of this therapeutic modality allows for the onset of gastrointestinal function spontaneously (often over prolonged periods of time) without nutritional deprivation. Intestinal atresias almost always are easy to identify in babies with gastroschisis. Extensive dissection and mobilization of this friable intestine is contraindicated in those babies in whom an atresia is not obvious but only suspected. In such cases the gastroschisis defect should be managed by whatever method is deemed appropriate and the baby observed while receiving intravenous nutritional support. If an atresia is present, it can be managed later in the baby's course by resection and primary anastomosis.

Two critically ill neonates with severe renovascular hypertension as a complication of aortic monitoring catheter are presented. They did not respond to intensive medical therapy for hypertension. In spite of their precarious general condition, nephrectomy was undertaken with complete relief of symptoms.

Ecchymosis of the scrotum and lower abdominal wall occurred in four newborn boys. All were anemic. Three had coagulation abnormalities and evidence of sepsis. In two, group B streptococcal septicemia was documented. Intraperitoneal hemorrhage from a ruptured subcapsular hematoma of the liver was the source of blood in the scrotum in three, and most probably in the fourth as well. Two infants died in spite of antibiotics, vigorous blood replacement, including exchange transfusion, and desperation laparotomies for continued intraperitoneal hemorrhage. Newborns with scrotal ecchymosis should be examined for intraperitoneal hemorrhage, ruptured subcapsular hematoma of the liver being the most probable source. Their coagulation status should also be evaluated, and sepsis should be suspected, especially in those with a demonstrated coagulopathy. Group B Streptococcus is a likely primary etiologic agent in these critically ill neonates. Nonoperative treatment, as given the two survivors in this experience, is preferred.

Neonatal sepsis due to group B beta-hemolytic Streptococcus (GBS) is reported to occur in about 1 out of 330 live births. Right-sided Bochdalek hernia (RBH) occurs in about 1 of 20,000 live births. The combination of group B streptococcal sepsis and delayed appearance of a right Bochdalek hernia is an infrequently reported phenomenon--18 patients have been previously reported in the English literature. We add four patients from our own experience to these previous reports. Since approximately 10% to 15% of the newborn population are exposed to group B Streptococcus we suspect that the inadequate diaphragmatic motion on the side of the Bochdalek hernia predisposes the child to development of septicemia and/or pneumonitis. Once the etiology has been established and appropriate antibiotic therapy instituted, progressive improvement in the patient's course should be seen. This is in contrast to a very significant mortality rate in many of the patients having early onset GBS. Any child, therefore, surviving early onset GBS only to deteriorate again, should be suspected of having an associated right Bochdalek hernia, and diagnostic steps should be taken to evaluate the integrity of the right diaphragm.

Tracheal agenesis is a rare cause of respiratory distress in the neonatal period. Temporary survival depends on ventilation through the esophagus. Thirty-eight case reports of tracheal agenesis (including one from this institution) have appeared in the literature. In this paper, we present the case reports of our 2 patients and review the literature. Tracheal agenesis is associated with a wide variety of congenital anomalies, the most frequent being ventricular septal defect. A new classification encompassing seven types of tracheal agenesis is described.

There are conflicting views on the pathogenesis of the intestinal malfunction seen in infants with gastroschisis. It has been variously ascribed to abnormalities of ganglion cells and smooth muscle elements, intestinal ischemia, and the "peel" which invests the serosa of the intestine. Review of the clinical and experimental literature showed only limited information on the histology of the eviscerated human intestine. In order to add to this data base, and to further investigate the pathogenesis of the intestinal malfunction from a histologic standpoint, we reviewed surgical and autopsy material from our experience with 105 neonates with gastroschisis. Ten specimens were satisfactory for evaluation from a standpoint of tissue integrity. The specific mural components of mucosa, submucosa, muscularis, and ganglion cells were examined and found to be either normal, or to show nonspecific abnormalities that varied from case to case, and were related mostly to intestinal infarction due to compromise of the gut at the site of the gastroschisis defect. In six patients, this progressed to atresia formation. The most consistent abnormalities were found in the serosal layer with its peel. Using special stains, the peel was found to be composed largely of fibrin and collagen. Based on this study, we feel that edema and ischemic changes, though often present, are much less prominent than the peel, as the leading histologic abnormality of the intestine of gastroschisis. Squamous epithelial cells were seen in the peel in four cases, suggesting that the peel had been "appliqued" onto the serosa of the herniated fetal gut.

The technique of anterior fundoplication for gastroesophageal reflux originally described by Alan Thal has been used in our institution in 605 patients. The description of the technique is the purpose of this paper. A brief description of the results in these 605 patients are also presented.

The anterior fundoplication described by Thal has been used in treating gastroesophageal reflux surgically in 362 children at The Children's Mercy Hospital and at St. Luke's Hospital in Kansas City, Missouri, because medical therapy had failed or was inappropriate. Long-term results have been evaluated in regard to relief of reflux and relief of symptoms attributed to reflux. Of the 335 patients followed from 1 to 8 years, 90% had a satisfactory initial result. Five percent required reoperation for a recurrence of reflux due to failure of the fundoplication or development of a hiatus hernia. All recurrences developed with 5 months of the initial operation. Fifteen of 335 patients (4.5%) had persistent symptoms despite correction of the gastroesophageal reflux; in these patients, attributing the symptoms to reflux was incorrect. There were no deaths in this series of patients as a result of operation. The success rate of the Thal fundoplication in children compares favorably with that of the Nissen Fundoplication.

Ninety cases of esophageal atresia (EA) with double tracheoesophageal fistula (TEF) from the literature and 4 new cases are examined. The incidence may be more common than is generally recognized with incidences up to 5.3% reported. The pre-, intra-, and postoperative diagnosis may be difficult, and half have been missed initially with almost half of these being first recognized at autopsy. During repair of EA and TEF the proximal esophagus should be mobilized looking for a proximal fistula. Many proximal TEF are missed at the initial operation and discovered in the postoperative period. The symptoms, diagnosis and treatment of the unrecognized proximal TEF are similar to that for isolated TEF. Results should be good since this problem occurs in large babies with fewer and less complex associated conditions.

A case of congenital posterior urethral perineal fistula is reported. The English literature is reviewed and anatomical findings, embryology, presenting signs and symptoms, and treatment are discussed.

Two patients were observed who had transient quadriceps paresis following local inguinal block for postoperative pain control following inguinal herniorrhaphy.

Necrotizing enterocolitis (NEC) usually occurs in low birth weight infants who have had perinatal stress, and the mortality remains significant. There are a few reports of NEC in the postoperative period, especially in young infants. Nine neonates developed NEC following operations and form the basis of this report. The interval between operation and the diagnosis of NEC varied from 3 days to 4 mo. The surgical lesions included one case each of esophageal atresia, tetralogy of Fallot, supralevator rectal atresia with rectourethral fistula, and multiple intestinal atresias. Three babies had gastroschisis and two had "apple peel" intestinal atresia. Only 3 of the 9 survived. The usual clinical findings of NEC, abdominal distention, bile stained gastric residuals and diarrhea (with or without blood), can occur in the postoperative period without NEC and are, therefore, not reliable diagnostic signs. Significant changes in the clinical course of these babies occurred from 7 hr to 5 days before the diagnosis was established. In these patients the roentgen findings that established the diagnosis of NEC included intestinal ileus, pneumatosis intestinalis, and portal vein gas. Pneumatosis intestinalis and portal vein gas were the most reliable diagnostic signs, but appeared relatively late in the course of the disease. In one case pneumatosis was seen only in retrospect. None of the patients had definite pneumoperitoneum. Awareness of NEC as a potential postoperative complication may result in early recognition, treatment and survival.

It is evident from studies of boys who suffered a surgical catastrophe at a young age and were then assigned a female sex role that cultural and environmental influence are a potent determinant of a child's gender identity. It is imperative that parents have their child's sex assignment firmly fixed in their minds as early as possible. Early surgical correction of a child with ambiguous genitalia to conform to the sex of assignment will serve greatly to reinforce appropriate behavior in the parent. Such surgical intervention for diagnostic and reconstructive purposes is both desirable and safe in the first weeks of life.

Twelve patients with gastroesophageal reflux following repair of esophageal atresia are presented. Reflux produced recurrent stricture, failure to thrive, repeated pneumonitis, and in one patient, respiratory arrest and nearly death. Treatment consists of positional therapy or fundoplication operation both of which seem less successful in this combination of lesions than with GER and a normal esophagus. There was one death as a late postoperative complication of fundoplication.

Hepatic hemangioma (hemangioendothelioma) is a benign vascular tumor with significant morbidity and mortality. Two newborn infants underwent partial hepatectomy for treatment of massive hepatic hemangioma, one with atrial septal defect and secondary congestive heart failure, and the other with symptomatic marked hepatomegaly. Cardiopulmonary bypass with induced deep hypothermic circulatory arrest was used in both patients in order to facilitate resection and prevent sudden massive blood loss. One infant also had closure of an atrial septal defect in addition to the partial hepatectomy. Both infants survived without complication and showed complete resolution of preoperative symptoms. This technique coupled with the use of fibrin glue is of value in infants with large hepatic hemangiomata and cardiac decompensation in the neonatal period.

An operative procedure for the management of rectal prolapse is described. It has the advantanges of simplicity, relative safety, short hospitalization, and lack of recurrence in the four patients presented.