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Biomedical subjects

N A Myers

Publications and source records attributed to N A Myers.

At least 19 recordsLinked to original sources

Intrinsic innervation of the oesophagus in fetal rats with oesophageal atresia.

Although the aetiology of oesophageal dysmotility after repair of oesophageal atresia and tracheo-oesophageal fistula (OA-TOF) remains controversial, oesophageal dysmotility also is present in isolated TOF or OA before surgery, suggesting a congenital cause. Our previous work with a model of OA-TOF in fetal rats demonstrated an abnormality in the course and branching pattern of the vagus nerve. However, little is known about the intramural nervous components of the atretic oesophagus. The intrinsic innervation of the atretic oesophagus was examined by immunohistological staining to see if there is an abnormality that might account for dysmotility. OA-TOF was induced in fetal rats by injecting adriamycin intraperitoneally into pregnant rats. Forty-eight controls, 40 OA-TOF, and 6 treated fetuses without OA-TOF were recovered. Whole-mount preparations of each oesophagus were stained with fluorescent antibodies against neuron-specific enolase (NSE), vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP). Compared with control fetuses, the density of the nerve plexus, ganglia, and number of cell bodies per ganglion immunostained by NSE, VIP, or SP was significantly reduced in OA-TOF fetuses. CGRP-immunoreactive nerve fibres in the oesophageal wall of both control and OA-TOF animals were found to be connected with extrinsic nerve bundles. No plexus-like nerve fibre network was observed. The results of the present study demonstrated significant abnormalities of the intramural nervous components of the oesophagus in OA-TOF fetal rats, involving both the excitatory (SP-labelled) and inhibitory (VIP-labelled) intramural nerves. These abnormalities may underlie the oesophageal dysmotility seen in OA-TOF patients.

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↗

Babies born with major disabilities: the medical-legal interface.

This article explores some of the legal and medical issues that confront doctors, lawyers, ethicists, and families when faced with the problems of a baby born with one or more major disabilities. Attitudes vary widely, and these are emphasised by cultural and social aspects in different parts of the world. Although the legal issues vary, in a large number of countries there appears to be less variation than with the medical issues.

Australia↗

The relationship between ethics and phronesis.

The management of a baby born with a major disability presents one of the most significant ethical problems faced at the end of the second millenium. These problems concern the individual baby and its family, but society as a whole is and must be involved in their resolution. This article explores these issues as they impact on the contemporary surgeon confronted with changing medical, technical, and ethical considerations.

Congenital Abnormalities↗

Apoptosis in tracheoesophageal embryogenesis in rat embryos with or without adriamycin treatment.

PURPOSE: The aim of this study was to determine whether apoptosis participates in separation of the foregut into trachea and esophagus and to evaluate the potential role of apoptosis in the development of esophageal atresia and tracheoesophageal fistula (EA + TEF) induced by Adriamycin. METHODS: Timed-pregnant rats were injected daily with either saline or Adriamycin (2 mg/kg) intraperitoneally on days 6 to 9 of gestation. Paraffin sections were prepared from 31 experimental and 31 control embryos at days 12 and 13 of gestation. Condensed nuclei were identified on the paraffin sections using the TUNEL method. Apoptosis was quantified by counting the positively stained cell nuclei in transverse sections of embryos. RESULTS: In day 12 control embryos the number of apoptotic nuclei in both lateral ridges of the foregut was high (15.67 +/- 1.38) but relatively low (4.17 +/- 0.80) in Adriamycin-treated embryos (P< .0001). In day 13 Adriamycin-treated embryos, the number of apoptotic nuclei in the region of the upper esophageal pouch was extremely high (23.78.5 +/- 2.20) compared with no detectable apoptotic nuclei in the control embryos. CONCLUSIONS: Apoptosis is required for normal tracheoesophageal embryogenesis and may be an important mechanism to be involved in the embryological development of esophageal atresia and tracheoesophageal fistula.

Animals↗

Timing and embryology of esophageal atresia and tracheo-esophageal fistula.

BACKGROUND: The embryology of tracheo-esophageal anomalies is controversial. The development of an adriamycin-treated animal model has enabled improved understanding of the embryogenesis of these anomalies. Using this model, we aimed to describe the events leading to esophageal atresia and tracheo-esophageal fistula. METHODS: Timed-pregnant Sprague-Dawley rats were injected daily with adriamycin intraperitoneally at a dose of 2 mg/Kg on days 6-9 of gestation. Histological sections were prepared from 96 experimental and 34 control rat embryos at 11-14 days gestation (plug day = day 0). RESULTS: The tracheal bud failed to develop normally from the foregut, leaving the foregut to give origin to both bronchi and differentiate into the respiratory system, and then continue as a fistula to the lower esophageal segment. Dorsal pouching of the proximal foregut, which is seen clearly on day 13, is responsible for the development of the upper esophageal segment. CONCLUSIONS: We conclude that failure of the tracheal bud to develop normally from the primitive foregut is the main event which leads to the tracheo-esophageal anomalies. As the proximal part of the primitive foregut develops primarily into a trachea rather than an esophagus, the anomaly of the esophagus could be described as agenesis instead of atresia.

Animals↗

Cardiovascular malformations in rat fetuses with oesophageal atresia and tracheo-oesophageal fistula induced by adriamycin.

Associated congenital anomalies have emerged as the most significant prognostic factor in babies born with oesophageal atresia and/or tracheo-oesophageal fistula (OA-TOF). The most frequently encountered groups of anomalies are cardiovascular (CV) and gastrointestinal, the former being more significant from a prognostic point of view. Some, such as a right-sided aortic arch (RAA), vascular ring, or major heart defects, may alter the timing and surgical approach for the repair of OA-TOF or adversely affect the prognosis. The rat fetal OA model induced by adriamycin (Adr) has been described previously. In the present experiments, information was sought regarding the incidence and type of CV abnormalities in fetal rats obtained from Adr-treated dams. OA-TOF was induced in 24 of 36 fetal rats from Adr-treated dams. DV abnormalities were found in 18 (75%) OA-TOF fetuses and 10 (83%) Adr-treated fetuses without OA-TOF. The difference was not significant (P >0.05). The most frequently found anomalies were ventricular and atrial septal defects. A RAA was present in 8/36 fetuses and a double aortic arch in 2/36. A patent ductus arteriosus was present in all treated fetuses compared with two-thirds of controls. The findings in the present study emphasise the importance of CV anomalies in association with OA, and reinforce the value of the Adr-induced rat fetal OA model by adding to our knowledge of the basic embryogenesis of both OA and CV anomalies.

Abnormalities, Multiple↗

Tracheomalacia with esophageal atresia and tracheoesophageal fistula in fetal rats.

BACKGROUND: Many patients who have esophageal atresia and tracheoesophageal fistula (EA-TEF) have associated tracheomalacia, which is thought to be one of the reasons for respiratory complications after surgical correction of the abnormality. METHODS: In this study, tracheas from Adriamycin-induced EA-TEF fetal rats were examined histologically and relevant cross-sectional parameters of the tracheas were measured. RESULTS: The tracheal lumen in tracheomalacia was small and irregular, losing its normal "D" shape. In most rats, the cartilaginous ring was broken into two to four segments, making the trachea lose its rigid support. The submucosa was thickened with prominent bulging of its membranous part into the tracheal lumen. The ratio of the inner luminal cross-sectional area to the outer tracheal cross-sectional area in EA-TEF rats was 15.7%, compared with a control ratio of 47.2%. In EA-TEF rats, the length of the cartilaginous ring was significantly shortened (P < .001), but not the length of membranous trachea, thus resulting in a cartilaginous/membranous (C/M) ratio of 1.55:1, markedly lower than that of normal rats (4.34:1, P < .001). The reduction of anterior-posterior diameter of the tracheal lumen was more marked than that of the transverse diameter. CONCLUSIONS: These observations suggest that the trachea in EA-TEF rats has a smaller lumen and is more flaccid than normal, making it prone to airway obstruction. The fact that tracheomalacia developed only in fetuses who had EA-TEF indicates that the factors that result in EA-TEF also cause tracheomalacia.

Airway Obstruction↗

The vagus and recurrent laryngeal nerves in the rodent experimental model of esophageal atresia.

BACKGROUND: After surgical correction of their esophageal atresia and tracheoesophageal fistula (EA-TEF), many patients exhibit evidence of esophageal dysmotility. Controversy exists as to whether the esophageal motility disorders result from denervation caused by surgery or from an inherent abnormal innervation of the esophagus. METHODS: The present study used an Adriamycin-induced EA-TEF fetal rat model to trace the course and branching of both the vagus and recurrent laryngeal nerves. Abnormalities observed in EA-TEF rat fetuses include: (1) fewer branches from both recurrent laryngeal nerves; (2) deviation of the left vagus from its normal course below the aorta, passing behind the fistula to approach and join with the right vagus to form a single nerve trunk on the right side of the esophagus; (3) relatively few branches from the single vagal nerve trunk (composed of fibers of the left and the right vagus) on the surface of the lower esophagus. CONCLUSIONS: Fetuses affected by EA-TEF have inherent abnormalities in the course and branching pattern of the vagus nerves as they descend through the thorax, culminating in a deficient extrinsic nerve fiber plexus in the lower esophagus. These observations may account for the esophageal motility disorders seen in patients who have EA-TEF even before surgical intervention.

Animals↗

A debt to Alexis: the Beaumont-St Martin story.

This paper is based on the book Experiments and Observations on the Gastric Juice and the Physiology of Digestion, originally published in 1833. The book held in the Cowlishaw Collection of the Royal Australasian College of Surgeons is the Edinburgh edition of 1838, which contains a preface by Andrew Combe, MD. The paper explores several aspects of the Beaumont-St Martin story, from St Martin's original injury and the primary care undertaken by Dr William Beaumont, whose numerous studies of the actions and reactions of the stomach were made possible because St Martin was left with a permanent gastric fistula. While the debt we owe to Beaumont is often acknowledged, patients are not mere machines and surgeons must recognize that surgery also owes a debt to its patients; in this case, to Alexis St Martin for what he permitted by way of experiment.

Canada↗

He who cannot take part in the friendly meal is half cut off from the society of man.

The history of oesophageal surgery is reviewed with particular reference to the early history of ingested foreign bodies, oesophagotomy and oesophageal stricture. Some emphasis is placed on those conditions, which are of particular significance in childhood. A brief mention is also made of the history of carcinoma fo the oesophagus.

Esophageal Diseases↗