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Biomedical subjects

S W Beasley

Publications and source records attributed to S W Beasley.

At least 37 records · Page 2Linked to original sources

Apoptosis during regression of the tailgut and septation of the cloaca.

PURPOSE: Apoptosis is involved in the embryonic morphogenesis of many organs. The current study was undertaken to ascertain the role of apoptosis during cloacal development in the rat. METHODS: One hundred five rat embryos, ranging from gestational days 11 to 16, were sectioned serially in the transverse or sagittal planes and stained with H&E. The cloaca, urorectal septum, rectum, urogenital sinus, Wolffian ducts, and tailgut (TG) were examined consecutively in temporospatial sequence. RESULTS: The tailgut immediately distal to the hindgut starts to regress by apoptosis on day 12 of gestation in a craniocaudal direction and has regressed completely by day 13.5. A large number of apoptotic cells and debris can be identified in the urorectal septum during cloacal septation. Vacuoles are formed by coalescence of apoptotic cells at the tip of urogenital sinus from day 15 to 16, and, at the same time, sporadic apoptotic bodies in the anal membrane contribute to its thinning. CONCLUSION: Results of the current study confirm that apoptosis occurs in a specific temporo-spatial sequence in the hindgut and cloaca and appears to be an important mechanism in TG regression, uro-rectal separation, urethral opening, and rupture of the anal membrane.

Animals↗

Temporospatial aberrations of apoptosis in the rat embryo developing esophageal atresia.

BACKGROUND/PURPOSE: Recent work has shown that apoptosis is a key component of the normal development of the foregut. This study was designed to compare the patterns of apoptosis in the normal foregut with those in the fetus developing esophageal atresia and tracheoesophageal fistula (EA-TEF) using 3-dimensional reconstructive techniques. METHODS: Timed pregnant rats that received no treatment (control group) or received Adriamycin intraperitoneally (experimental group) had their embryos removed between days 11 and 14 of gestation. The embryos were sectioned serially and stained with H&E. Three-dimensional reconstructions were made of the foregut and areas of apoptosis were marked on them to facilitate analysis of apoptotic patterns. RESULTS: Apoptosis was evident in control embryos in the region in which tracheoesophageal separation occurs from days 12 and 12.5. Experimental embryos showed no apoptosis until day 13 when apoptosis was observed immediately posterior to the foregut within the esophageal mesenchyme and in the laryngeal mesenchyme ventral to the foregut. CONCLUSIONS: The pattern, timing and location of apoptosis in rats developing EA-TEF is abnormal. Our work indicates that it is actually a complete lack of apoptosis at the crucial stage of development that leads to this abnormality rather than an alteration in the patterning of apoptosis at this crucial time. The observation of apoptosis only within the mesenchyme raises the possibility that apoptosis in the foregut developing EA-TEF may be a reaction to that abnormal development rather than its cause.

Animals↗

The acutely painful scrotum in children: how to avoid the traps in diagnosis.

The acutely painful scrotum is one of the more common surgical emergencies in the prepubertal boy. It is almost always caused by torsion of a testicular appendage or torsion of the testis. It may be difficult to distinguish the two conditions clinically with certainty. Where torsion of the testis has occurred, delay in diagnosis and treatment increases the likelihood that the testis will be found dead at the time of surgical exploration. This review identifies the main causes of diagnostic error and describes how the various traps in clinical assessment can be avoided.

Acute Disease↗

Pathohistological study of adriamycin-induced tracheal agenesis in the fetal rat.

There have been few studies of tracheal agenesis (TA) because it is an extremely rare condition and is invariably fatal. However, it is recognised to be associated with a variety of oesophageal abnormalities, including oesophageal atresia (OA) and communicating bronchopulmonary foregut malformations (CBPFM). Except for some gross pathological reports, there has been no detailed histological investigation of this congenital abnormality. Adriamycin-induced TA in fetal rats provides a means of studying this uncommon condition, including its relationship to oesophageal abnormalities. TA was induced in rat features by intra-peritoneal injection of adriamycin (2 mg/kg) into timed-pregnant rats on days 6-9. Their 33 fetuses were removed by caesarean section, cut transversely, and stained after which the slides were examined. OA developed in 27/33 adriamycin-treated fetuses, TA occurred in 5. Four had type III while the 5th had type II TA. The oesophagus of fetuses with TA acquired tracheal features in the region where both ectopic bronchi originated. Two fetuses with TA also had OA, and 4 had a CBPFM. Other abnormalities detected involved the gastrointestinal, urinary and cardiovascular systems. The association of TA and oesophageal abnormalities suggests that there may be a spectrum of abnormalities comprising a number of variants, which may have a common aetiology. The other abnormalities co-existing in this animal model mirror those found in reported cases of human TA. Ultimately, the rat model of OA and TA may give insight into the embryogenesis of these malformations.

Abnormalities, Drug-Induced↗

Gastric perforation in infants with oesophageal atresia and distal tracheo-oesophageal fistula.

Gastric perforation (GP) is a well-recognised complication of oesophageal atresia (OA) with distal tracheo-oesophageal fistula (TOF), and is usually associated with extreme prematurity, hyaline membrane disease, and the requirement for assisted ventilation. The presentation is sudden, and leads to further deterioration in respiratory function because of increasing abdominal distension from pneumoperitoneum and splinting of the diaphragm. Unrelieved, the infant becomes increasingly hypoxic and may die. A review of six infants with OA and distal TOF in whom GP occurred has enabled us to develop the following guidelines for the appropriate initial surgical management of this complication: (1) Needle paracentesis of the abdomen en route to surgery if the infant continues to deteriorate; (2) Urgent laparotomy to decompress the abdomen and to occlude the lower oesophagus with a catheter introduced through the GP; (3) Thoracotomy and division of the fistula; (4) Oesophageal anastomosis if the infant's condition improves sufficiently and the anatomy is favourable; and (5) Repair of the GP and formation of a gastrostomy.

Abnormalities, Multiple↗

The frequency, significance, and management of a right aortic arch in association with esophageal atresia.

An unrecognised right aortic arch (RAA) found at thoracotomy may complicate the repair of oesophageal atresia (OA) and tracheo-oesophageal fistula (TOF). This paper analyses the patient characteristics, peri-operative management, and outcome of 16 infants with a RAA, and proposes management guidelines. Between 1948 and 1996, 709 patients with OA/TOF were admitted to the Royal Children's Hospital, of whom 13 had a RAA. Three additional cases from two other paediatric surgical units were included. All 16 case records were reviewed retrospectively. The overall incidence of RAA in OA was 1.8%. Neither a chest radiograph in 16, nor antenatal ultrasonography in 7 detected a RAA. Post-natal echocardiography (ECHG) detected a RAA in only 1 of 7 infants examined; that patient underwent repair of the OA through a left (L) thoracotomy. The other 15 infants underwent initial right (R) thoracotomy. Six of these had a complete repair from the R side and 5 had division of the fistula only; 2 of these 5 had initial division of the fistula, and the OA was repaired through a repeat R thoracotomy 4 and 7 weeks later. In the remaining 4 infants where the fistula could not be located at the initial R thoracotomy, complete repair proved possible through the L chest. Three of these infants underwent an immediate L thoracotomy; the 4th had a delayed L thoracotomy 1 week later. There were 6 deaths: these occurred early in the study and were related to severe prematurity, congenital heart disease (CHD), and post-operative respiratory complications. CHD was identified in 11 of 16 infants (71%). Routine pre-operative ECHG is unreliable in determining the laterality of the aortic arch. Should a RAA be encountered during a R thoracotomy for OA, it is often possible to divide the fistula and repair the OA from that side, but where repair looks potentially difficult it is wise to proceed to an immediate L thoracotomy.

Abnormalities, Multiple↗

Comparison of results of laparoscopic and open antegrade continence enema procedures.

Several modifications of the Malone antegrade continence enema (ACE) procedure have now been reported. In this study we have compared the results of our experience with the laparoscopic appendicostomy (LACE procedure) with the published results of previously described open ACE procedures. Children who had the LACE procedure at our institutions were reviewed. Intra- and postoperative problems were identified by review of hospital case notes and from a questionnaire completed by the children's caregivers. These results were compared with the reported results of the original Malone procedure, the Peña modification, and the open appendicostomy as described by Wilcox. Since 1994, 30 children have had LACE procedures performed at our institutions. Two have required conversion to an open procedure because of difficulty locating the appendix. The stoma is being used for regular antegrade colonic washouts in 29 of the 30, compared with 19 of 31 in Malone's series and 16 of 20 in Peña's. Improvement in soiling has been achieved in 27 (90%) of our patients, 15 of whom are completely clean, a rate similar to that of the other types of procedure (61%-78%). Stenosis of the stoma has occurred in 8 children (27%), compared with rates of 10%-33% in other series. Stomal leakage has been troublesome for 2 (6.7%), compared with leak rates between 5.6% and 15% in other series. The LACE procedure is technically the simplest. The laparoscopic approach to the ACE procedure appears to be a simpler and safe alternative to previously described methods. It causes minimal morbidity, has a high long-term viability rate, and resulted in improved control of soiling in 90% of the children with faecal incontinence in whom it has been employed.

Adolescent↗

Relationship of the notochord to foregut development in the fetal rat model of esophageal atresia.

BACKGROUND/PURPOSE: The notochord (Nt) is thought to act as a primary organizer for adjacent axial embryonic organs. The current study used the Adriamycin-induced fetal rat model of esophageal atresia and tracheoesophageal fistula (EA-TEF) to determine whether anomalies of the foregut (FG) were associated with an abnormal Nt. METHODS: Eight experimental female Sprague-Dawley rats received intraperitoneal injection of Adriamycin (1.75 mg/kg) on gestational days 6 to 9 inclusive, and 4 control rats received saline injection only. Their embryos were harvested on gestational days 11, 12, 13, and 14. Embryos from each age subgroup were serially sectioned and stained with H&E. The FG and Nt were traced from the primitive pharynx to the level of the stomach. RESULTS: By day 11, the Nt of control embryos had completely separated from the FG and was located immediately ventral to the neural tube. On gestational day 12, the Nt detached from the neural tube, and the trachea and esophagus were separating. On day 11, in the Adriamycin-treated embryos, the Nt was still attached to an FG that was narrowed or occluded. On day 12, the Nt remained adherent to the FG from the primitive pharynx to the level above the primitive respiratory buds, at which point it became thicker and branched sagittally, with the anterior branch contacting or merging with the FG. The FG usually loses its lumen or continuity when in contact with the Nt. CONCLUSIONS: Exposure of rat embryos to Adriamycin leads to abnormal development of the Nt, including prolonged attachment to or fusion with the FG, and abnormal branching. Traction on the FG by the Nt produces occlusion of its lumen and may result in its complete interruption. Separation of the Nt from the FG would appear to be a prerequisite for the normal development of the FG into its derivatives: the esophagus and trachea.

Animals↗

Communicating bronchopulmonary foregut malformations in the adriamycin-induced rat model of oesophageal atresia.

BACKGROUND: Communicating bronchopulmonary foregut malformations (CBPFM) are rare abnormalities of the development of the primitive foregut that result in an abnormal communication between the upper gastrointestinal tract and pulmonary tissue. They usually occur in isolation, but sometimes are seen in association with oesophageal atresia (OA). METHODS: Communicating bronchopulmonary foregut malformations were induced in the offspring of pregnant rats by intraperitoneal injection of Adriamycin (Delta West Pty Ltd, Bentley, Western Australia, Australia). Fetuses harvested by caesarean section were fixed in 10% formalin, transversely sectioned and stained with haematoxylin and eosin. Serial examination of the slides allowed three-dimensional reconstruction of the anatomy of the pulmonary system and the oesophagus. RESULTS: Communicating bronchopulmonary foregut malformations occurred in nine (30%) of fetuses with OA. Three types of CBPFM were produced: an isolated pulmonary structure (accessory lung) attached to the lower oesophagus via a patent bronchus (6 fetuses); an anomalous bronchus from the lower oesophagus to the lower part of the left lung (two fetuses); and atresia of the trachea (one fetus). CONCLUSIONS: These observations are consistent with the assertion that CBPFM and OA are variations of a spectrum of abnormalities and may have a similar aetiology. In the rat model it would appear that Adriamycin interferes with the timing and progression of lung bud differentiation at a time when the primitive foregut is developing rapidly. Ultimately, this model may shed light on the embryogenesis of both anomalies.

Animals↗

Early experience with the laparoscopic ace procedure.

BACKGROUND: In 1990 Malone et al. introduced the reversed appendicocaecostomy as a technique to enable an antegrade continence enema (ACE) to be administered. The aim is to achieve colonic emptying and thus prevent soiling in children with faecal incontinence. The procedure has been modified by suturing the opened appendix directly to the skin as a stoma, and can now also be performed laparoscopically. METHODS: All children undergoing laparoscopic ACE procedures at Christchurch Hospital, Christchurch, New Zealand and Princess Margaret Hospital, Perth, Australia, were reviewed. Intra-operative and postoperative problems were identified retrospectively and questionnaires were completed by the children's caregivers detailing their experience with managing their children following the ACE procedure. RESULTS: Thirty children have had a laparoscopic ACE procedure performed since 1994. Two required conversion to an open procedure because of difficulty locating the appendix. Twenty-nine children are currently using the stoma for regular antegrade colonic washouts. Improvement in continence was seen in 27 children, 15 of whom have been completely continent. Stenosis of the stoma occurred in eight children, two of whom required operative revision of the stoma; the others have been managed by daily dilatation, either with the irrigation catheter or a small perspex dilator. More recently, spatulating the appendix tip has reduced the incidence of stenosis. Two children have had troublesome leaks. CONCLUSIONS: The laparoscopic approach to the ACE procedure results in an improved level of continence in this difficult group of children with faecal incontinence. It is a simpler alternative to previously described methods and causes minimal morbidity. Results to date suggest a satisfactory outcome for both the children and their families.

Child↗

Does postoperative ventilation have an effect on the integrity of the anastomosis in repaired oesophageal atresia?

Several authors have claimed that the use of postoperative ventilation or graded withdrawal of respiratory support reduces the incidence of anastomotic complications after repair of oesophageal atresia, particularly where the gap between the oesophageal ends has been extensive or where the anastomosis has been constructed under tension. Careful review of their data reveals little objective evidence to either support or refute this contention. Many institutions are achieving low leakage rates following oesophageal anastomosis in oesophageal atresia, but to date there has been no controlled study to show that the use of neck flexion, muscle paralysis, intubation and assisted ventilation postoperatively influences the integrity of the anastomosis. The sequence of observations that led to the presumed relationship between postoperative ventilation and oesophageal leak is reviewed. It would appear that the effect of postoperative ventilation and paralysis on the oesophageal anastomosis is yet to be determined.

Anastomosis, Surgical↗

The clinical implications of non-idiopathic intussusception.

A pathological lesion can be identified at the leadpoint of intussusception in about 6% of episodes. Occasionally, general manifestations of an underlying disease indicate the specific cause of an intussusception (e.g., perioral pigmentation in Peutz-Jeghers syndrome), but usually the clinical features provide no clues as to the aetiology. Neonatal intussusception may be caused by a duplication cyst or Meckel's diverticulum. Beyond 12 months, the proportion of intussusceptions due to a pathological lesion at the leadpoint increases with age. There is an identifiable lesion in the majority of children over 5 years of age. Postoperative intussusception accounts for between 0.5% and 16% of intussusceptions, although it has a variety of causes; it typically follows retroperitoneal dissection. It is unusual for an intussusception due to a pathological lesion at the leadpoint to be reduced by enema. If it is reduced, the lesion may be seen at the time of reduction or fluoroscopy, or subsequently on ultrasonography.

Age of Onset↗

Perforation during gas reduction of intussusception.

Perforation during attempted gas-enema reduction of intussusception is more common than during a barium enema. In a review of 650 consecutive attempted gas enemas, perforation occurred in 7 infants (1.1%). Gross abdominal distension from the pneumoperitoneum may be rapid and cause splinting of the diaphragm, which leads to acute respiratory distress. This complication is readily recognised at the time of the gas enema, and may require immediate intervention by paracentesis using a 14-gauge needle. A review of 7 children with intussusception in whom perforation occurred revealed that all had radiologic evidence of bowel obstruction (air-fluid levels) prior to the enema, and the patients had had a relatively long history since the onset of symptoms. No perforation occurred during a delayed repeat enema reduction. Perforation during gas enema produces minimal peritoneal contamination. No pathological lesion at the lead point of the intussusception was identified in any of the children in whom perforation occurred.

Enema↗