Biomedical subjects

J M Hutson

Publications and source records attributed to J M Hutson.

At least 19 recordsLinked to original sources

PubMed1999

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↗

PubMed1999

Visceral anomalies in prenatally adriamycin-exposed rat fetuses: a model for the VATER association.

Adriamycin is teratogenic if given to pregnant rats. A wide range of anomalies involving the gastrointestinal, renal, and cardiovascular systems has been described, similar to the VATER association, yet it is not known if they are identical to the human pattern. The aim of this study was to document the visceral anomalies in rat fetuses exposed to adriamycin and to determine their similarities with the congenital defects in humans with the VATER association. The results revealed a spectrum of very similar anomalies. Furthermore, the characteristics of the tracheo-oesophageal anomalies had a lot of features in common with the human pattern. We conclude that the adriamycin-treated fetal rat is an excellent model for studying the VATER association.

Abnormalities, Drug-Induced↗

PubMed1998

Does the gubernaculum migrate during inguinoscrotal testicular descent in the rat?

BACKGROUND: The role of the gubernaculum in descent of the testis is controversial. The mechanism of testicular descent has been studied in the rat, because inguino-scrotal descent occurs postnatally in this species. Several authors have claimed that the cremasteric sac forms by eversion of the gubernacular cone, whereby regression of the extra-abdominal part of the gubernaculum creates a space into which the gubernacular cone everts to form the processus vaginalis within the scrotum. This postulated lack of any gubernacular migration phase contrasts with the situation in the human, where gubernacular migration appears to be an integral component of testicular descent. This study was designed to determine in the rat whether there is any gubernacular migration toward the scrotum during testicular descent, or whether eversion of the cremasteric sac alone could account for the extension of this sac into the bottom of the scrotum. METHODS: Oblique sagittal sections of the inguino-perineal region were taken from rats aged 21 days of gestation and days 1, 3, 4, 6, 8, and 10 days postnatally. Histological sections were examined and the following measurements were obtained: gubernacular cone height, gubernaculum-scrotum distance, processus vaginalis length, and pubic symphysis-anus distance. RESULTS: The gubernaculum was not in close proximity to the developing scrotum at any age. After 21 days of gestation, there was little evidence of a substantial gubernacular bulb distal to the processus vaginalis. At all ages the gubernacular cone height was significantly less than the distance from the gubernaculum to the scrotum. CONCLUSIONS: These results show that the gubernaculum does not develop in close proximity to the developing scrotum. Even if complete eversion of the gubernaculum takes place, the gubernaculum would still fail to reach the bottom of the scrotum. It is proposed that gubernacular eversion is more apparent than real and that some degree of gubernacular migration is needed for complete extension of the cremasteric sac to the bottom of the scrotum.

Animals↗

PubMed1998

Embryogenesis of tracheal atresia.

A spectrum of tracheo-esophageal anomalies has been described in an adriamycin-treated model with common features to the human pattern. Tracheal agenesis was part of this spectrum. It is a rare congenital anomaly that has not been described in embryos. Virgin timed-pregnant Sprague-Dawley rats were injected with adriamycin i.p. at a dose of 2 mg/Kg on days 6-9 of gestation (plug day = day 0). Fetuses were recovered at term and histologic assessment of tracheo-esophageal anomalies was made. Also, embryos were removed on different gestational days and the embryology of these defects was analysed. Two out of sixty-two fetuses and nine out of 180 embryos were identified with tracheal atresia. Type III tracheal atresia was seen in the full-term fetuses with a tracheo-esophageal fistula arising from the origin of the left main bronchus. Day 13 embryos did not show normal tracheal development; instead, the lung buds developed from the ventral aspect of the foregut which continued to the stomach as a lower esophageal segment. A blind ending pouch was seen on the ventral aspect of the upper part of the foregut. The embryogenesis of tracheal atresia was similar to that of esophageal atresia except that the blind upper foregut pouch developed ventrally rather than dorsally.

Abnormalities, Drug-Induced↗

PubMed1998

Skeletal anomalies in the adriamycin-exposed prenatal rat: a model for VATER association.

Vertebral and radial anomalies are prominent features of VATER (vertebral defects, anorectal anomaly, tracheoesophageal fistula with esophageal atresia, and radial dysplasia) association. It has been shown that exposure of the rat fetus to adriamycin produces a spectrum of anomalies, including esophageal atresia and other features of VATER association. We aimed to document the skeletal defects found in rats exposed to teratogenic doses of adriamycin in utero. Vertebral, rib, and limb anomalies were found in 54, 54, and 35% of these examined fetuses, respectively. The range of bone lesions seen in this animal model was similar to the range of lesions seen in infants born with VATER association.

Abnormalities, Drug-Induced↗

PubMed1998

Intestinal rotational abnormalities in polysplenia and asplenia syndromes.

OBJECTIVE: To review the anomalies of intestinal rotation occurring in association with asplenia (right isomerism) and polysplenia (left isomerism) syndromes. MATERIALS AND METHODS: A retrospective study was performed of 27 children with asplenia (21) or polysplenia (6) identified from the cardiology and radiology databases from 1988 to 1996 and in whom an upper gastrointestinal barium study had been performed. The intestinal rotation was determined by reviewing the barium meal and could be divided into four groups: (1) normal rotation, (2) incomplete rotation or nonrotation, (3) reversed rotation and (4) reversed incomplete rotation or nonrotation. Surgical correlation was obtained at laparotomy in 17 patients. RESULTS: Of the 27 children studied, 3 (11 %) had normal rotation; incomplete rotation or nonrotation occurred in 5 (19 %), and 2 in this group developed midgut volvulus; 5 (19 %) had reversed rotation; 14 (52 %) had reversed incomplete rotation or nonrotation. CONCLUSION: Asplenia and polysplenia are frequently associated with intestinal malrotation, and a barium study is recommended in all of these children, as many will be at risk of midgut volvulus.

Abnormalities, Multiple↗

PubMed1998

Distributions of substance P- and VIP-immunoreactive nerve fibres in the colonic circular muscle in children.

In children with severe chronic constipation, abnormal distribution of substance P (SP) and vasoactive intestinal peptide (VIP), which represent excitatory and inhibitory nerves, respectively, has been reported. The normal distribution of these neuropeptides, however, is not well known. The aim of this study was to determine the populations of SP- and VIP-immunoreactive nerve fibres in the circular muscle of the colon in children. Surgically resected specimens were collected from a 6-year-old girl with familial polyposis coli (total colon) and nine patients with anorectal malformations aged 0-4 years (sigmoid colon). Double-labelling immunofluorescence was employed using neuron-specific enolase (NSE) with SP and NSE with VIP to count the percentage of SP- or VIP-labelled nerve fibres. These specimens showed normal submucous and myenteric plexuses stained with NSE. The population of SP- immunoreactive fibres was 15%-21% throughout the colon, and VIP was 39% in the caecum and 63%-65% in the transverse, descending, and sigmoid colon. In the four neonatal specimens (day 1 to 4), the SP population was only 1%-6% and the VIP population was also low (22%-33%). After 3 weeks of age, the populations had stabilised at 18%-26% for SP and 52%-62% for VIP. SP-immunoreactive nerve fibres were scarce in the neonatal period, and showed a rapid increase by 3 weeks and a similar though less dramatic increase in VIP-immunoreactive fibres. VIP-immunoreactive fibres were fewer in the caecum that at other colonic levels, where they accounted for 60% of NSE-labelled fibres; the SP population, however, was comparable at all levels of the colon at about 20% of NSE-labelled fibres.

Adenomatous Polyposis Coli↗

PubMed1998

Ventriculo-peritoneal shunts in children reveal the natural history of closure of the processus vaginalis.

PURPOSE: Little information is known about the natural history of closure of the processus vaginalis. The authors studied children who had ventriculoperitoneal shunts to determine the natural history of closure of the processus vaginalis and to better understand the role of intraabdominal pressure in the etiology of congenital inguinal hernia. MATERIALS AND METHODS: A retrospective review of all children undergoing insertion of ventriculoperitoneal shunts between 1985 and 1995 at the Royal Children's Hospital was undertaken. In each case, the sex, the cause of hydrocephalus, the age at insertion of the shunt, and the subsequent development of an inguinal hernia or hydrocele was recorded. RESULTS: There were 430 children in the study. An inguinal hernia developed in 15% of children after insertion of a ventriculoperitoneal shunt, and a hydrocele developed in an additional 6% of boys. Inguinal hernias were bilateral in 47% of boys and 27% of girls. The incidence of subsequent development of an inguinal hernia or hydrocele was closely related to the age of insertion of the ventriculoperitoneal shunt, being 30% during the last 8 weeks of gestation and the first few months of life, then falling quite sharply to reach about 10% at 1 year. CONCLUSIONS: The high occurrence of inguinal hernias and hydroceles after ventriculoperitoneal shunt insertion supports the role of raised intraabdominal pressure in the etiology of these conditions. It appears that raised intraabdominal pressure is associated with an increased incidence of clinical hernias, but not with increased incidence of patency of the processus vaginalis. The development of an inguinal hernia or hydrocele after insertion of a ventriculoperitoneal shunt can be used as an indirect marker of patency of the processus vaginalis at the time of insertion of the shunt. From this, we propose that the processus vaginalis remains patent in at least 30% of children in the first few months of life, after which time the patency rate appears to fall off quite sharply.

Female↗

PubMed1998

Relationship between esophageal atresia with tracheoesophageal fistula and vertebral anomalies in mammalian embryos.

BACKGROUND/PURPOSE: The association of esophageal atresia with tracheoesophageal fistula and vertebral anomalies is well known, although the embryology of the combined defects has not yet been analysed. The present study describes the origin and development of esophageal atresia with tracheoesophageal fistula and vertebral anomalies in embryos using a rat model of VATER association produced by Adriamycin administration. RESULTS: The lung buds were seen to develop from the laryngotracheal groove but the trachea failed to grow normally and the foregut overgrowth compensated for this failure. The trachea developed by trachealization of the foregut, which continued as a fistula to the lower esophageal segment. The notochord did not separate from the foregut at the correct time (before day 11 in rat embryos, Carnegie stage 11 in human embryos). Overgrowth of the foregut ventrally and caudally carried with it the attached notochord in the same direction leading to abnormal bending of this structure. CONCLUSION: This irregularity of the notochord may be responsible for abnormal development of the vertebrae.

Abnormalities, Drug-Induced↗

PubMed1998

Anatomical relationship between urethra and clitoris.

PURPOSE: We investigated the anatomical relationship between the urethra and the surrounding erectile tissue, and reviewed the appropriateness of the current nomenclature used to describe this anatomy. MATERIALS AND METHODS: A detailed dissection was performed on 2 fresh and 8 fixed human female adult cadavers (age range 22 to 88 years). The relationship of the urethra to the surrounding erectile tissue was ascertained in each specimen, and the erectile tissue arrangement was determined and compared to standard anatomical descriptions. Nerves supplying the erectile tissue were carefully preserved and their relationship to the soft tissues and bony pelvis was noted. RESULTS: The female urethra, distal vaginal wall and erectile tissue are packed into the perineum caudal (superficial) to the pubic arch, which is bounded laterally by the ischiopubic rami, and superficially by the labia minora and majora. This complex is not flat against the rami as is commonly depicted but projects from the bony landmarks for 3 to 6 cm. The perineal urethra is embedded in the anterior vaginal wall and is surrounded by erectile tissue in all directions except posteriorly where it relates to the vaginal wall. The bulbs of the vestibule are inappropriately named as they directly relate to the other clitoral components and the urethra. Their association with the vestibule is inconsistent and, thus, we recommend that these structures be renamed the bulbs of the clitoris. CONCLUSIONS: A series of detailed dissections suggest that current anatomical descriptions of female human urethral and genital anatomy are inaccurate.

Adult↗

PubMed1998

Renal tuberculosis in an Australian-born child.

This report describes a case of renal tuberculosis, complicated by hypertension and ureteric obstruction, in a previously well Australian born child. Despite antituberculous chemotherapy and ureteric stenting, there was a progressive loss of renal function in the right kidney until surgical nephrectomy allowed full recovery. A high level of clinical suspicion is necessary for a diagnosis of genitourinary tuberculosis. Ureteric cicatrisation and obstruction occasionally may occur with healing, and therefore serial renal tract imaging during treatment is necessary to detect this complication.

Child↗

PubMed1998

Efficacy of orchidopexy on spermatogenesis in the immature mutant 'trans-scrotal' rat as a cryptorchid model by quantitative cytological analysis.

OBJECTIVES: To determine whether cryptorchidism is a congenital malformation and whether the impaired spermatogenesis in immature testes can be reversed by early orchidopexy, using the mutant trans-scrotal (T-S) rat which is normally masculinized but has cryptorchidism in 85% of males. MATERIALS AND METHODS: First, T-S rats (six per group) with ectopic testes destined to be undescended were investigated histologically at 4, 7 and 14 days after birth. Secondly, 12-day-old T-S rats were divided into four groups which underwent different procedures, i.e. 1, with normally descending testes (normal control, 10 rats); 2, with undescended testes (UDT) treated by orchidopexy (treated UDT, eight rats); 3, with UDT treated by a sham operation (sham-operated UDT, six rats); and 4, with UDT left untreated (untreated UDT, six rats). Thirty days after operation the testicular anatomy was recorded; excised testes were examined histologically and different types of germ cells were counted per tubule cross-section microscopically. RESULTS: There were no quantitative or morphological differences in the numbers of gonocytes, type-A spermatogonia or Leydig cells in the seminiferous tubules between normal and ectopic testes in the first 14 days after birth. However, by 21 days of age spermatogenesis in the UDT had declined with transformation from primary leptotene spermatocytes to spermatids. There were significantly more Leydig cells in the untreated UDT at 30 days than in normal control testes. The impaired spermatogenesis in UDT was restored by early orchidopexy and there were significantly more seminiferous tubules at stage 3 (pachytene spermatocytes) and stage 4 (spermatids) than in the untreated or sham-operated groups (P < 0.001). CONCLUSIONS: These results show that in the T-S rat with cryptorchidism, the testicular damage is not a congenital malformation and can be reversed with early surgical correction.

Animals↗

PubMed1998

Temperature sensitivity of primary spermatocyte DNA synthesis in immature mice confirmed by bromodeoxyuridine labelling in vitro.

OBJECTIVE: To investigate the relationship between temperature and DNA synthesis of immature germ cells and to determine whether the early primary spermatocytes proliferate at a 'scrotal' temperature of 32 degrees C in vitro. MATERIALS AND METHODS: Day-7 mouse testes (n = 16) were cultured with 10% fetal calf serum (FCS) for 3 days at 32 degrees C or 37 degrees C and labelled by bromodeoxyuridine (BrDU) for a further hour. The BrDU-labelled cells were detected by immunohistochemical staining using a monoclonal anti-BrDU antibody. The numbers of primary spermatocytes with BrDU-labelling or unlabelled in each tubule were determined as an index of spermatocyte DNA synthesis. In addition, the cultured media at different temperatures were collected and the testosterone levels measured by radioimmunoassay. RESULTS: The numbers of primary spermatocytes (P < 0.01) and the BrDU-labelling index in primary spermatocytes per tubule at 32 degrees C in vitro were significantly higher (P < 0.001) than in the culture at 37 degrees C. The testosterone levels in the culture media at 32 degrees C were also markedly higher than in the culture at 37 degrees C (P < 0.01). CONCLUSION: These observations indicate that DNA synthesis of early primary spermatocytes and testosterone production can be stimulated by lower testicular temperature, even in immature mouse testes that are naturally located in the intra-abdominal cavity.

Animals↗

PubMed1998

Paediatric surgical training: a system that works.

BACKGROUND: Paediatric surgical trainees going through the system at the Royal Children's Hospital (RCH), Melbourne, have been impressed with the amount of time dedicated to postgraduate training compared with other institutions. They generally felt well prepared to sit for Fellowship examinations. We decided to look at the programme offered at the RCH and objectively assess the results. METHOD: A review was undertaken of the training system at the RCH. Opinions were sought from recent and current trainees and compared with trainees in other disciplines. Figures were obtained from the RACS Examinations Office with respect to pass rates at Fellowship examinations. RESULTS: The training programme is outlined in some detail. A total of 79% of candidates passed their FRACS in paediatric surgery while at the RCH since 1985, compared with 52% from all other institutions. CONCLUSIONS: A successful training programme requires a commitment to educate one's junior colleagues. Busy consultants can contribute actively by offering to teach and by encouraging their trainees to attend rounds and tutorials. The rewards are better-educated and well-rounded surgeons as well as, hopefully, a higher pass-rate at the Part 2 examination.

Education, Medical, Continuing↗

PubMed1998

Congenital undescended testes in neonatal pigs and the effect of exogenous calcitonin gene-related peptide.

PURPOSE: We investigated the neonatal piglet as a possible animal model for cryptorchidism and to determine whether calcitonin gene-related peptide (CGRP), which has been proposed to regulate inguinoscrotal testicular descent, could induce testicular descent in piglets with congenital cryptorchidism. MATERIALS AND METHODS: We examined 38 cryptorchid piglets to document the anatomy in 8 and to investigate the role of CGRP in 30. The 2-week-old piglets were allocated randomly to receive a mini-osmotic pump containing CGRP at various concentrations or phosphate buffered saline. The pump was inserted surgically into the ipsilateral scrotum, with the contents blinded to the surgeon. The positions of the testes, pump and anatomical landmarks were measured and photographed. The pigs were sacrificed and dissected 2 weeks later, and the positions were remeasured and photographed. The testes were examined histologically. RESULTS: The 3 variants of cryptorchidism observed were intra-abdominal in 20 cases, inguinal in 9 and lateral inguinal ectopic in 9. CGRP had no effect on intra-abdominal or ectopic testes. In contrast, for inguinal testes exogenous CGRP caused a slight but significant 10 +/- 7.9 mm. descent towards the pump in 5 cases compared to -2.9 +/- 5.8 mm. in 4 controls. CONCLUSIONS: Exogenous CGRP stimulated migration of inguinal testes that had been arrested in the line of descent while ectopic testes did not respond. These results support a role for CGRP in testicular descent and suggest that a slow release depot preparation might be useful as a possible treatment in some forms of cryptorchidism.

Animals↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

Histopathologic study of esophageal atresia and tracheoesophageal fistula in an animal model.

A histopathologic study of tracheoesophageal anomalies was conducted on an Adriamycin-treated animal model to determine how closely it resembles the human pattern. Adriamycin was administered (2 mg/kg body weight) to timed-pregnant rats on days 6 through 9 of gestation. The fetuses were recovered at term, dissected and prepared for histological studies. Dissection showed a similar range of variants of tracheoesophageal anomalies as seen in humans. Esophageal atresia with distal tracheoesophageal fistula was by far the most common type. Other varieties were seen such as esophageal atresia without a fistula, tracheal atresia and hypoplastic esophagus with atrophic mucosa, and muscle coat. Serial sectioning of the distal segment showed tracheobronchial elements extending to a variable distance from the origin of the fistula.

Abnormalities, Drug-Induced↗