Biomedical subjects

J M Hutson

Publications and source records attributed to J M Hutson.

At least 19 recordsLinked to original sources

PubMed2001

Investigation of the intra-abdominal oesophagus and hiatus in fetal rats with oesophageal atresia and tracheo-oesophageal fistula.

After surgical management of their oesophageal atresia (OA) and tracheo-oesophageal fistula (TOF), most patients exhibit evidence of gastro-oesophageal reflux (GOR) and many have oesophagitis. However, the aetiology of the GOR is still controversial. This study was undertaken to document whether there are congenital abnormalities in the intra-abdominal oesophagus and the hiatus in the fetal rat with OA and TOF following exposure to adriamycin (ADR). Time-pregnant rats were injected daily with either saline or 2 mg/kg ADR intraperitoneally on gestational days (GD) 6-9. The fetuses (n = 56) from 8 litters were harvested on GD 21 for examination. The length of the oesophagus between the diaphragmatic crura and the gastro-oesophageal junction (GOJ) and the sizes of the stomach and the oesophageal hiatus were measured under a dissecting microscope. The length of the oesophagus between the diaphragmatic crura and the GOJ in the ADR-treated fetuses (0.85 +/- 0.37 mm) was significantly shorter than in control fetuses (2.41 +/- 0.32 mm) (P < 0.0001). The size of the stomach in ADR-treated fetuses (5.30 +/- 1.01 mm) was significantly smaller than in the controls (8.07 +/- 0.49 mm) (P < 0.001). Moreover, the size of the oesophageal hiatus in ADR-treated fetuses (1.16 +/- 0.43 mm) was markedly larger than in the controls (0.32 +/- 0.1 mm) (P < 0.0001). These results showed that the congenital abnormalities in ADR-treated rat fetuses may account for the oesophageal functional disorders seen after surgical correction in patients who have OA and TOF.

Abnormalities, Drug-Induced↗

PubMed2001

Ontogeny of bladder agenesis in rats induced by adriamycin.

OBJECTIVES: To determine the anatomical steps leading to bladder agenesis in rats prenatally exposed as fetuses on gestational days (GD) 6-9 to adriamycin. MATERIALS AND METHODS: Timed-pregnant Sprague-Dawley rats were injected intraperitoneally with adriamycin at 2 mg/kg (n = 28) on GD 6-9 (vaginal plug = day 0). The control group (n = 21) received saline. Fetuses were harvested on GD 10, 11, 12, 13, 14, 15 and 16. Serial paraffin sections were prepared from a minimum of 10 experimental and five control fetuses at each gestational age, and stained with either trichrome or haematoxylin and eosin, and examined by light microscopy. RESULTS: In the control group the urorectal septum first became visible and the mesonephric ducts apparently abutting the anterior cloaca on GD 12. The presumptive urinary bladder was clearly defined on GD 14. On GD 15, the common excretory ducts became incorporated into the newly formed urogenital sinus and the ureters opened into the bladder. In the treated animals, beginning on GD 11, the undivided cloaca was noticeably smaller and by GD 13-14, the vesical extension of the urogenital sinus was conspicuously absent. Instead, opposite ureters joined to drain directly into the proximal blind-ending urethra or the persistent distal urogenital sinus. CONCLUSIONS: Prenatal exposure of rat fetuses to adriamycin resulted in primary agenesis rather than secondary resorption of the bladder. The ontogeny showed that the mechanism underpinning bladder development is unique and is under the influence of factors that can be targeted by adriamycin. Further work will elucidate the unique nature of bladder organogenesis and should have important applications in future research into artificial bladders.

Abnormalities, Drug-Induced↗

PubMed2001

Undescended testis is accompanied by calcitonin gene related peptide accumulation within the sensory nucleus of the genitofemoral nerve in trans-scrotal rats.

PURPOSE: Recent data suggest that calcitonin gene related peptide (CGRP) released from the sensory branch of the genitofemoral nerve may regulate testicular descent. We studied the number of CGRP immunoreactive cells in the sensory nucleus of the genitofemoral nerve (L1 to L2 dorsal root ganglia) in cryptorchid trans-scrotal rats. Four-week-old trans-scrotal rats with unilateral undescended testis underwent bilateral genitofemoral nerve dissection and retrograde nerve labeling with the fluorescent dye 4,6-diamidino-2-phenylindole (DAPI). Animals were sacrificed 48 hours later and the L1 to L2 dorsal root ganglia were removed. Serial sections were obtained and double fluorescent labeled with antibody to CGRP. Retrograde labeled and CGRP immunoreactive cells were counted using an epi-fluorescent microscope. In the 6 male trans-scrotal rats evaluated we noted a mean plus or minus standard deviation of 1,272 +/- 98 retrograde labeled dorsal root ganglion cells ipsilateral to a fully descended testicle, including 98 +/- 34 that were also CGRP immunoreactive. On the side of the undescended testis there was a mean of 1,600 +/- 304 DAPI positive cells and 160 +/- 51 CGRP immunoreactive, DAPI labeled cells. The difference was significant (p <0.02). This study shows that in trans-scrotal rats the sensory nucleus of the genitofemoral nerve contains more CGRP immunoreactive cells ipsilateral to an undescended testis than on the contralateral side, highlighting the significance of CGRP supply through the sensory branch of the genitofemoral nerve for testicular descent.

Animals↗

PubMed2001

Leydig insulin-like hormone, gubernacular development and testicular descent.

PURPOSE: Testicular descent is controlled by 2 morphological and hormonal steps. Transabdominal testicular descent is mediated by gubernacular swelling and regression of the cranial suspensory ligament. Müllerian inhibiting substance (MIS) has been proposed to stimulate the swelling but this remains controversial. Recently, a mouse mutant for Leydig insulin-like hormone (Insl3) was found to have undescended testis and deficient gubernaculum. We examine the testicular position of Insl3 mutant mice and the development of gubernacula. MATERIALS AND METHODS: Mice with Insl3 homozygotes (-/-), heterozygotes (+/-) and wild-types (+/+) were examined at embryonic day 16.5 and birth. Macroscopic dissections and measurements of the testicular position, as well as microscopic analysis (hematoxylin and eosin, and Masson's trichrome) were performed. RESULTS: Of the mice 11 Insl3 homozygote males had significantly impaired testicular descent at embryonic day 16.5 and birth (p <0.01), and the cord was thin and elongated, while 14 heterozygotes and 7 wild-types had normal testicular descent. Microscopically, the gubernaculum of Insl3 homozygotes was small with some muscle development but no central core of mesenchyme at embryonic day 16.5. On the other hand, heterozygotes and wild-types had normal gubernacular development with a swelling reaction. CONCLUSIONS: Insl3 mutants show feminized gubernaculum with deficient mesenchymal core. Insl3 appears to have some role in the gubernacular swelling reaction in mice.

Animals↗

PubMed2000

The suspensory ligament of the clitoris: connective tissue supports of the erectile tissues of the female urogenital region.

We aimed to define the gross anatomy of the supporting structures of the clitoris. We performed a dissection of the perineum of a series of 22 female and four male cadavers. Specific dissection of the clitoral and penile suspensory ligament complex was performed in four female and two male cadavers. Serial written observations and photography were used to document the findings. Our findings were then compared with the anatomical description of these structures in the historical and current anatomical literature. The suspensory ligament of clitoris consistently displayed two components: a superficial fibro-fatty structure extending from a broad base within the mons pubis to converge on the body of the clitoris and extending into the labia majora: in addition there is a deep component with a narrow origin on the symphysis pubis extending to the body and the bulbs of the clitoris. The supporting structures of the clitoris are more substantial and complex than previously described. Their shape, extent, and orientation are different from analogous structures of the penis, the suspensory ligament of which was found as described in the literature.

Adolescent↗

PubMed2000

Apoptotic cell death and fertility in three unilateral cryptorchid rat models.

Three rat strains have been studied, using a sensitive apoptotic detection method for germ-cell degeneration, to resolve the controversy regarding the effect of cryptorchidism on the contralateral descended testis (CDT). Sprague Dawley and Buffalo rats were made cryptorchid by operation at 20-22 days of age, while trans-scrotal (T-S) rats were a congenitally unilateral cryptorchid strain. Sham operated rats or normal T-S littermates were used as controls. Experiments were performed over a period ranging from 2 weeks to 18 months. Testis weight was assayed, as was the detection of apoptosis by agarose gel laddering and immunohistochemistry by using the TUNEL method. Labeled cells in 150 cross-sectioned testis tubules were counted on the TUNEL stained slides and the mean number of labeled cells per tubule was calculated. Paternity studies on Sprague Dawley and T-S rats were carried out at 12 and 24 weeks of age to assess fertility by the resultant number of pregnancies and litter sizes. Both Sprague Dawley and T-S rat models showed a biphasic distribution of apoptosis levels. This biphasic distribution was not observed in Buffalo rats as they were only studied at later time points (12-20 weeks). A significant effect on either testis weight or apoptosis in the CDT compared with the control descended testis (P > or = 0.1) has not been found in these three cryptorchid models, and the present results are discussed with reference to observations of other researchers in rodents and humans. While the cryptorchid testis showed a high level of labeled apoptotic cells per tubule in all rat strains, fertility was not affected and remained the same as controls at 12 and 24 weeks. There was, however, a marked strain difference in fertility in T-S as compared with Sprague Dawley rats. After 24 weeks of cryptorchidism, both control and cryptorchid T-S rats had a 44% pregnancy incidence compared with a 90% pregnancy incidence in Sprague Dawley rats. In addition, litter size in T-S control and cryptorchid rats were small compared with those of Sprague Dawley rats at 12 and 24 weeks.

Animals↗

PubMed2000

Balanitis xerotica obliterans with urethral stricture after hypospadias repair.

Three cases of urethral stricture due to balanitis xerotica obliterans (BXO) after hypospadias repair are reported. The first patient showed white, dense scarring on the prepuce before the hypospadias repair and developed a stricture of the urethra after the operation. The second and the third were uneventful for 6 and 2 years, respectively, after the hypospadias repair, and then developed urethral strictures. Pathologic diagnosis of the stenotic lesion is essential. Complete excision of the affected urethra with topical steroid ointment or sublesional triamcinolone injection is recommended for this condition. Although the complication of BXO after hypospadias repair is rare (3 out of 796 cases with hypospadias in our series), surgeons need to be aware of this condition as a cause for late onset of urethral problems.

Balanitis↗

PubMed2000

Fusion of childhood inguinal hernia induced by HGF and CGRP via an epithelial transition.

BACKGROUND/PURPOSE: Recent evidence has suggested that calcitonin gene-related peptide (CGRP), which is released from the genitofemoral nerve, may trigger fusion of the patent processus vaginalis in children with inguinal hernia. The purpose of this study was to determine whether CGRP triggers the release of mesenchymal factors leading to subsequent fusion of the processus vaginalis. METHODS: The response of cultured epithelial cells derived from the patent processus vaginalis was analysed by a novel in vitro culture system. Epithelial cells lining fresh hernial sacs (removed at inguinal herniotomy) were detached enzymatically and cultured for 72 hours on Micropore filters, in the presence of either 100 ng/mL hepatocyte growth factor (HGF), 7.4 x 10(-6) mol/L CGRP (amino acids 1 to 37), 7.4 x 10(-6) mol/L CGRP (8 to 37) antagonist, 10% fetal calf serum (FCS), or serum-free medium (SFM) alone. Transformation from an epithelial cell morphology to motile mesenchymal fibroblast-like cells was assessed by an average migration score (AMS), ranging from 0 with no sign of migration, to 3 with greater than 75% of cells migrating. Confocal microscopy was used to record changes in expression of epithelial (cytokeratin) and mesenchymal (vimentin) markers, as well as actin. Beta-catenin also was examined because it is part of the molecular complex that links cadherins to actin resulting in cell-cell adhesion. RESULTS: Epithelial and mesenchymal markers underwent either down-regulation or up-regulation as epithelial cell sheets broke apart and individual cells commenced migration. The AMS after 72 hours of culture was 0.22 with SFM (control); with FCS the score was 1.4 (P < .01). The AMS score with CGRP (1 to 37) was 0.55 (P = .165) and with its analogue, CGRP (8 to 37), which is a competitive inhibitor, 0.67 (P = .309). Neither was significant. HGF caused a significant increase in the AMS to 1.56 (P = .01). CONCLUSION: Both HGF and FCS (which contains various undefined peptides and growth factors) produced transformation of hernial sac epithelial cells, whereas CGRP and its inactive analogue did not. CGRP receptors are localised to mesenchymal fibroblasts within the processus vaginalis connective tissue, suggesting that CGRP could act indirectly via HGF, which, in turn, promotes fusion of the processus vaginalis. In the future, a nonsurgical treatment of inguinal herniae in children might be possible by the local administration of agents which promote fusion.

Actins↗

PubMed2000

Does the sensory nucleus of the genitofemoral nerve have a role in testicular descent?

BACKGROUND/PURPOSE: A role for the genitofemoral nerve (GFN) and its neurotransmitter, CGRP, in testicular descent has been well established. The exact mechanism, however, by which circulating androgens act on the GFN is not yet known. The authors studied the sensory nucleus of the GFN (L1-L2 dorsal root ganglia [DRG]) to determine whether it is sexually dimorphic and able to be influenced by intrauterine antiandrogen treatment. METHODS: Sprague-Dawley rats were injected daily with 100 mg/kg/d of the antiandrogen flutamide on day 16 to 19 of pregnancy. Control animals were treated with vehicle only. At the age of 2 to 3 days the newborn rats underwent unilateral dissection of the GFN. The proximal end was labelled with fluorescent dye, diamidinophenyl indole. The rats were killed 48 hours later, and the relevant ganglia (L1,L2) were removed. Cryostat frozen serial sections were cut, and retrogradely labelled fluorescent cells were counted under an epifluorescence microscope. In 32 animals, the cells were double fluorescent labelled with antibody to CGRP and FITC. RESULTS: Of 75 rats evaluated, the mean number of the DAPI-positive, retrogradely labelled cells in the control groups was 266 +/- 55 in the male, and 230 +/- 67 in the female as opposed to 186 +/- 45 and 161 +/- 35 in the flutamide-treated male and female groups, respectively. In 32 animals the DRG sections were double labelled for CGRP. The number of CGRP plus DAPI-positive cells were as follows: control males, 60 +/-12; control females, 50 +/- 9; flutamide males, 36 +/- 8; flutamide females, 40 +/- 10. CONCLUSIONS: These findings show a sexual dimorphism in the number of GFN cell bodies in the DRG. Flutamide decreases the number of GFN cell bodies in the DRG of both males and females. Our results are consistent with a role for circulating androgens acting on the sensory nucleus of the GFN (DRG) instead of the motor nucleus as previously thought. The release of CGRP from the nerve endings may occur via the sensory branch of the GFN.

Androgen Antagonists↗

PubMed2000

Cloacal and urogenital malformations in adriamycin-exposed rat fetuses.

OBJECTIVES: To determine the spectrum of cloacal and urogenital malformations in rat fetuses prenatally exposed to adriamycin, which causes abnormalities that strongly resemble the VATER association (vertebral defects, anal atresia, tracheo-oesophageal fistula with oesophageal atresia, renal defects and radial limb dysplasia) in humans, and to evaluate how closely such anomalies resemble those seen in humans. MATERIALS AND METHODS: Timed-pregnant rats were injected intraperitoneally with adriamycin at 6-9 days of gestation; a control group received saline only. Fetuses (35 treated and 30 control) were recovered at 21 days of gestation, and examined macroscopically and microscopically for cloacal and urogenital abnormalities. RESULTS: All the treated fetuses had no bladders and severe hydroureter/hydronephrosis on one or both sides. Male fetuses had a proximal blind-ending urethra communicating with dilated ureters and giving rise to vasa. Female fetuses had a persistent urogenital sinus communicating with the ureters and cervix/uterus; 57% of the treated group had an imperforate anus and some had recto-urethral fistulae (males) or recto-urogenital fistulae (females). CONCLUSION: Rat fetuses exposed to adriamycin have a spectrum of cloacal and urogenital anomalies (predominantly no bladder) which is more severe than those of the human VATER association. Nonetheless, this is an excellent animal model for the study of genitourinary embryology, especially bladder development.

Abnormalities, Drug-Induced↗

PubMed2000

Rectal mucosal biopsy compared with laparoscopic seromuscular biopsy in the diagnosis of intestinal neuronal dysplasia in children with slow-transit constipation.

BACKGROUND/PURPOSE: Intestinal neuronal dysplasia (IND) as a cause for severe chronic constipation remains controversial. The aim of this study is to examine the correlation between a deficiency of substance P (SP) immunoreactive nerve fibers in the colon and enzyme histochemistry of rectal biopsies in children with slow-transit constipation. METHODS: Fifty children with intractable constipation have been assessed by rectal biopsies examined with histochemical staining for lactate dehydrogenase, and 32 children among those 50 have been studied by laparoscopic seromuscular biopsy of the colon labelled with antibodies to SP using immunofluorescence methods. RESULTS: Four children have evidence of IND. Fifteen children, including all 4 IND cases, showed a deficiency of SP immunoreactivity. There is a significant correlation between giant ganglia and SP deficiency (P <.01). CONCLUSION: This study is attempting to propose that a deficiency of SP immunoreactivity in colonic circular muscle nerves may be used as a histologic marker for slow-transit constipation and that IND may be a small subset of patients with SP deficiency.

Adolescent↗

PubMed2000

Patterns of radial dysmorphology with the VACTERL association in the adriamycin-exposed prenatal rat.

The VACTERL association is an acronym for a constellation of abnormalities affecting the spinal column, anus, heart, trachea, esophagus, kidneys, and limbs that are seen in newborns. It has been shown that prenatal rats exposed to Adriamycin demonstrate a similar series of anomalies. It is the aim of this study to characterize the spectrum of limb anomalies in this model. Female Sprague-Dawley rats (N = 18; 14 experimental and 4 control) were used. After mating, pregnant animals received intraperitoneal injections of Adriamycin (2 mg per kilogram) on days 6, 7, 8, and 9 of gestation. Fetuses were recovered on day 21 of gestation. Ten experimental litters (42 fetuses) and two control litters (18 fetuses) underwent skeletal staining with Alizarin Red S stain. Four experimental litters (N = 18) and two control litters (N = 17) underwent histological study including staining for vascular and neural structures. Upper limb anomalies were found in 45% of the experimental animals, all including either hypoplasia or bending of the radius. The ulna was involved in 37% of the affected limbs. There were no isolated ulnar deformities. There were no histological differences noted. The spectrum of upper limb anomalies seen in the Adriamycin-exposed prenatal rat closely approximates, in incidence and morphology, the upper limb deformities seen with the VACTERL association in children. It is a reliable model for use in additional studies of the embryological mechanism by which these defects arise.

Abnormalities, Drug-Induced↗

PubMed2000

In vitro fusion of human inguinal hernia with associated epithelial transformation.

The processus vaginalis (PV) is a peritoneal diverticulum which forms to allow descent of the fetal testis to the scrotum. During human development fusion and obliteration of the PV often fails to occur with the result that inguinal hernias are the most prevalent congenital abnormality requiring surgery in childhood. Androgen is proposed to regulate testicular descent via the genitofemoral nerve which releases the neuropeptide calcitonin gene-related peptide (CGRP). It is possible that subsequent fusion of the PV and tissue remodelling following descent is indirectly controlled by androgen via CGRP action. An organ culture assay was developed to assess fusion of the PV taken from inguinal herniotomy in infants. Fusion was induced in vitro by CGRP but not by CGRP 8-37, CGRP 27-37 or dihydrotestosterone in equimolar concentrations. Fusion was accompanied by transformation of the epithelium, as shown by staining of intermediate filament proteins, cytokeratin and vimentin. Localization studies for CGRP receptors on 25 specimens indicated CGRP acts on mesenchymal fibroblasts but not directly on PV epithelium suggesting an indirect pathway. Hepatocyte growth factor/scatter factor was found to induce fusion of PV and may be involved as an intermediate molecule in the fusion cascade. This study represents the first approach to understanding the humoral control and underlying mechanism by which the PV fuses.

Animals↗

PubMed2000

Growth factor and somatic cell regulation of mouse gonocyte-derived colony formation in vitro.

At birth, the mouse gonocyte does not resume mitotic activity for several days in vivo but, in an in vitro clonogenic system, cell division commences soon after culture. Somatic testis cell underlays had potent inhibitory activity on gonocyte-derived colony formation (23 +/- 15% compared with 84 +/- 1% in controls; P = 0.0001) when added to cultures of gonocytes in vitro. A Sertoli cell line, TM4B, had an even more pronounced effect on gonocyte clonogenic capacity, with 1 +/- 1% compared with 72 +/- 17% colony formation in controls (P = 0.0003). Testis cells appeared to have a direct inhibitory effect since testis-conditioned medium did not show a significant reduction in the number of colonies. The observed reduction in colony formation with the testis cell underlay was not accounted for by decreased attachment of gonocytes as simultaneous addition of a single cell suspension of testis cells was still effective in significantly reducing colony number when compared with controls (P = 0.01). Therefore, the observed inhibition exerted by testis cells appears to be a consequence of decreased proliferation of gonocytes. Growth factors belonging to the transforming growth factor beta superfamily which are known to be expressed in testis, such as transforming growth factor beta and epidermal growth factor, did not exert any inhibitory action on gonocyte-derived colony formation when added together or alone. However, a shift to a smaller colony size occurred in the presence of transforming growth factor beta and transforming growth factor beta plus epidermal growth factor, indicating a reduction in colony cell proliferation. Evidence for the expression of the Müllerian inhibiting substance receptor on newborn gonocytes using in situ hybridization was inconclusive. This finding was in agreement with the lack of a direct action of Müllerian inhibiting substance on the formation of gonocyte-derived colonies in vitro. Leukaemia inhibitory factor, alone or in combination with forskolin, had neither an inhibitory nor an enhancing effect on gonocyte-derived colony formation. An in vitro clonogenic method to assay for the proliferation of gonocytes in the presence of specific growth factors, cell lines, testis cell underlays and cell suspensions was used to identify a somatic cell-mediated inhibitor which may be responsible for the inhibitory action on gonocyte proliferation in vivo shortly after birth.

Animals↗

PubMed1999

Effect of androgens on the cranial suspensory ligament and ovarian position.

Androgens have been postulated to have a major role in testicular descent via regression of the cranial suspensory ligament, which in normal rodents anchors the ovary to the retroperitoneum near the lower pole of the kidney. This study aimed to quantitate the degree of descent of the foetal ovary in androgen-treated female mice to determine the role of androgens in regression of the cranial suspensory ligament and descent of the testis. Time-pregnant mice were injected with testosterone propionate or methyl testosterone (2.5-3.0 mg) in vehicle on day 13 or 14. Control animals received vehicle only. Newborn mice were anaesthetised and dissected for macroscopic anatomy of the ovary, which was quantified by measuring the vertical distance from the lower pole of the kidney to the lower pole of the ovary. Histological analysis was also performed. The external genitalia were masculinised in all females exposed to prenatal androgens. The ovaries of treated animals were mobile, with no cranial suspensory ligament, and located slightly caudal to the kidney. Wolffian duct structures were identifiable, but the gubernaculum was qualitatively unchanged compared with control females. The ovary was displaced caudally (P< 0.001), but only 15-25% of the distance to the lower abdomen. Exogenous androgens induce regression of the cranial suspensory ligament, causing the ovary to be more mobile and lower in the abdominal cavity. However, since the testicular position at birth is at or below the bladder neck, androgen-mediated regression of the cranial suspensory ligament is only an adjunct to the control of transabdominal testicular descent.

Animals↗

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↗

PubMed1999

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↗