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BACKGROUND: Progressive nonsteroidal anti-inflammatory drug (NSAID) dose reduction appears logical; however, there is no evidence-based medicine indicating that efficacy is maintained as dose is reduced. OBJECTIVE: To determine if NSAID dose can be reduced and pain relief and mobility can be maintained in dogs with osteoarthritis (OA). ANIMALS: Client-owned dogs (n = 59) with OA-associated impaired mobility and pain. METHODS: Prospective, randomized, blinded study. After 14 days wash-out, dogs were randomized to reducing dose (RDG) (n = 30) or maintenance dose (MDG) (n = 29). MDG received standard dose meloxicam. RDG received a reducing dose from D28 onward, reducing to 0% of maintenance for the final 2 weeks. Assessments were at D14, 28, 42, 56, 70, 84, 98 and 112 using subjective owner assessments, accelerometry (AM), and standing percent body weight distribution (%BW). A Kaplan-Meier survival curve described how dogs dropped out because of insufficient pain control. A Log-rank test compared the groups. RESULTS: More dogs in RDG (13) dropped out because of owner-evaluated insufficient pain control compared with MDG (5) (P = .029; odds ratio: 3.67; median dropout time: 84 days in each group). For the dogs that did not drop out (n = 41), there were no significant differences between groups in owner assessments (P > .2 for each), %BW placed on the index limb (P = .750), or accelerometer-measured activity (P = .14). CONCLUSION AND CLINICAL RELEVANCE: Dose reduction is a less effective means of pain control compared with maintained dosing. However, NSAID dose reduction with maintained efficacy is possible, but success appears to be individual dog dependent.

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Seminomas are very rare tumours in children and adolescents. We describe a case of seminoma in a 15-year-old boy who was managed with orchidectomy but no adjuvant therapy. He remains relapse-free 8 years after surgery as determined by clinical, radiological and serological surveillance. This study emphasizes the uncertainty over the need for adjuvant treatment in the management of seminoma in the adolescent patient, in particular in prepubescent children.

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A case of urogenital nonunion is presented to illustrate the importance of laparoscopy for the impalpable testis. A 4-year-old boy with an impalpable left testis underwent laparoscopy. This revealed not only the vas deferens entering the deep inguinal ring but also a small intraabdominal testis supplied by the testicular vessels. Exploration of the inguinal canal revealed the vas deferens terminating in a nubbin of tissue. Histology identified epididymal structures both adjacent to the testis and in the terminal nubbin of the vas deferens. This is an example of urogenital nonunion. Complete separation of the vas and testis with epididymal structures attached to each is very unusual, with only four other cases reported. Laparoscopy should be the initial procedure for impalpable testis. A blind-ending vas deferens found on exploration of the inguinal canal might be taken as evidence of the vanishing testis syndrome. However, this conclusion should not be drawn unless laparoscopy has demonstrated testicular vessels entering the internal inguinal ring.

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PURPOSE: The aim of this study was to evaluate delayed elective resection of antenatally detected enteric duplication cysts. METHODS: A retrospective casenote study of intraabdominal cysts detected antenatally between January 1991 and January 2002 found 37 fetuses with cysts. Twelve were enteric duplications. Two were duodenal, 1 was an 85-cm tubular jejunoileal duplication, and 9 were ileocecal. Asymptomatic cysts were followed with serial ultrasound scars and resected electively over 14 months. RESULTS: Three neonates had small bowel obstruction demanding laparotomy: 1 of the 2 infants with duodenal duplication cysts, 1 infant with an ileocecal duplication, and the infant with the tubular duplication. One with an ileocecal duplication became symptomatic at 2 months and underwent a laparotomy. Seven had their duplications resected electively between 6 weeks and 14 months, and the other is still being followed. Four of the 7 asymptomatic duplications electively resected contained gastric mucosa. CONCLUSIONS: Intraabdominal enteric duplication cysts are increasingly likely to be detected antenatally. The majority are likely to remain asymptomatic for several months at least, after which a resection can be planned. The prevalence of gastric mucosa suggests that they should not be left indefinitely. Laparoscopically assisted resection of ileocecal duplications is safe and effective.

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OBJECTIVE: Limb-body wall complex (LBWC) is a rare fetal polymalformation of uncertain etiology, but it has been regarded as sporadic in nature with a low recurrence risk. We review a case series in light of recent evidence about possible genetic and environmental associations. METHODS: All abortions or births coded as limb-body wall defect or fetal acrania/exencephaly or with unclassified polymalformation between January 1996 and January 2001 were audited. RESULTS: During the 5-year period there were 33,286 live births in our region. Eleven cases met the criteria of LBWC giving an incidence of 0.33/1000 live births. In 50%, 50% and 30% of women a history of cigarette, alcohol and marijuana use, respectively, was noted. Furthermore, 40% of the women had a history of a previous infant with a congenital anomaly. One patient delivered two consecutive male infants with LBWC. CONCLUSIONS: Whilst the majority of cases of LBWC are sporadic, some women may have an underlying genetic predisposition. It may be prudent to advise against the use of alcohol, cigarettes and other drugs and to offer an ultrasound scan in a tertiary referral center in a subsequent pregnancy.

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The incidence of congenital diaphragmatic hernia (CDH) is 1:1,200-5, 000, and the condition is associated with high mortality and morbidity attributed principally to associated pulmonary hypoplasia. One treatment approach has been for intrauterine intervention to induce lung growth to a sufficient level to allow survival at birth. Repair of the hernia in utero has been attempted, using a method of immediate reduction and repair of the hernia (patch) compared to a slow reduction method using a silastic "silo" sewn over the diaphragm defect to contain the hernial contents. In animal studies, this second method has been associated with lower fetal morbidity and mortality. This study, utilizing the sheep model of CDH, focuses on analysis of lung structural development and maturation, comparing the efficacy of the immediate vs. slow methods of hernial repair in preventing/reversing pulmonary hypoplasia. We hypothesized that: a) Both the immediate (patch) and slow (silo) methods of hernia repair performed in the lamb model of CDH will stimulate lung growth and structural development and restore lung structure and maturity towards normal levels by term gestation; b) Effects will be detectable by morphometric measurement of the following parameters: lung volume; parenchyma to nonparenchyma tissue ratio; volume density of connective tissue in nonparenchyma; gas exchange tissue to airspace ratio; gas exchange surface area; capillary loading; alveolar/airspace density; and alveolar perimeter; c) Effects will be seen in all lobes of the lung; and d) There will be no significant difference in lung size or structural parameters between the two groups. Forty-four pregnant ewes were allocated randomly to one of four groups. Fetal lambs in three groups (n = 36) underwent CDH creation at days 72-74 of gestation. Of surviving lambs showing an adequate hernia, 9 were not operated on further, 11 underwent "repair" using a silastic chimney around the hernial contents (slow reduction), and 11 underwent "repair" by a silastic patch over the diaphragmatic defect (immediate reduction). The fourth group were normal controls. All surviving lambs (n = 8 in each group) were delivered by Cesarian section at 141-143 days (term = 145-149 days). Lungs were obtained at autopsy, inflation-fixed, divided into lobes, and sampled, and morphometric analysis was performed. Comparisons were made between these groups and with matched normal controls and CDH untreated animals prepared in conjunction and previously reported. The lungs from the CDH animals treated by both methods of fetal hernia repair showed significant lung growth and structural development and maturation, although they remained significantly hypoplastic compared to normal. There were minor differences in the lung parameters between these two groups, with a tendency for the slow method to provide more normal parameter values. An exception was the increase in lung volume that was greater for the immediate (patch) method, particularly in the left lower lobe. In conclusion, intrauterine hernia repair by both methods is capable of partially reversing total lung and lobar structural hypoplasia and immaturity. The slow reduction method, with reduced potential for mortality and morbidity, is at least as good at reversing pulmonary hypoplasia as the immediate method. Alternative intrauterine interventions to prevent or reverse pulmonary hypoplasia are discussed and compared with the hernia repair methods used in this study.

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A study was undertaken of childhood deaths caused by fires in South Australia over a 10-year period from 1989 to 1998. A total of 23 deaths of children occurred with an age range of 2 months to 16 years (mean 5 years 10 months; M:F = 13:10). Fourteen deaths were associated with house fires, four with fires in cars and four were miscellaneous or unspecified. While house fire deaths remained the major cause of childhood fire deaths (65%), deaths in car fires accounted for a significant proportion of cases (17%). Although the numbers are small, cars represented a specific danger because of their confined space with highly flammable interiors, lockable doors, and built in non-childproof lighters. Cars should not be regarded as suitable places to leave young children, or for children to play in unsupervised.

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This study tested whether concordance could be achieved for abnormal inflammation in the basal decidua of placental specimens among 6 pathologists experienced in placental pathology. Thirty microscope slides were evaluated by the pathologists for chronic deciduitis. They also scored the severity and extent of inflammation and the presence of plasma cells. No definition of chronic deciduitis was provided. Concordance (5/6 or 6/6 agreement) was achieved in 23 cases (76%). Spearman's rank correlation showed that the diagnosis of chronic deciduitis was almost identical to the assessment of the severity of the inflammation. A regression analysis showed that the perception of severity (and hence chronic deciduitis) was influenced by the other 2 variables, extent and plasma cells. The results were shared with the pathologists, and 25 cases (excluding those with previous 6/6 consensus) were reevaluated. Concordance was now achieved in the 83% of those remaining cases. Using a threshold based on the severity and the extent of lymphocytes, and the presence of plasma cells, pathologists are able to diagnose chronic deciduitis with sufficient concordance to be of value in clinical correlation studies.

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We describe 17 children with non-alcoholic steatohepatitis. All had elevated levels of serum liver enzymes and 16 were morbidly obese. Liver biopsy showed variable steatosis and fibrosis in nine patients. At follow-up, 12 of 14 patients had persistent morbid obesity and 11 had elevated liver enzyme levels.

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Congenital diaphragmatic hernia (CDH) in humans carries high mortality/morbidity attributed to associated pulmonary hypoplasia. An understanding of the effects of CDH on fetal lung growth is important for development of successful treatments. This study aimed to quantitate structural differences between normal and CDH-affected preterm lamb lungs. We hypothesized that (a) pulmonary hypoplasia is present in preterm CDH-affected lungs; (b) the relative degree of pulmonary hypoplasia increases with gestation; and (c) the left upper lobe (LUL) is affected most. Fetal lambs were allocated to two groups. One group underwent surgery (72-74 days gestation) inducing CDH. Both groups (n = 7, n = 7) were delivered by cesarean section at 129 days (term: 145-149). Lungs were obtained at autopsy, were inflation-fixed, processed for histology, and morphometry was performed. Preterm lungs of CDH-affected lambs in comparison to those of normal lambs demonstrated a reduction in the following: lung weight (37.7 g vs. 116.3 g); lung weight:body weight (0.012 vs. 0.040); fixed lung volume (33.6 ml vs. 96.9 ml); gas-exchange surface area (4.56 m(2) vs. 13.70 m(2)); parenchyma:nonparenchyma (59:41 vs. 72:28); and parenchymal airspace:tissue (16:84 vs. 35:65). Non-parenchyma connective tissue was increased (58%), airspaces were more numerous (1077/mm(2)) and smaller (perimeter 76.6 microm), gas-exchange surface density (2394 cm(-1)) was greater and capillary loading (0.04 ml/m(2)) was reduced compared to preterm normal lung (49%; 778/mm(2); 108.7 microm; 2003 cm(-1), 0.11 ml/m(2), respectively). The LUL was affected most. These data quantitate pulmonary hypoplasia in preterm CDH-affected lambs. Comparisons with published data indicate increasing relative hypoplasia as gestation proceeds. Fetal interventions will affect lung development, depending on timing, with intervention still likely to be worthwhile during late gestation.

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Postnatal lung development in the tammar wallaby was investigated using transmission electron microscopy and stereological morphometry. Volume densities of interstitial, epithelial and endothelial tissue and capillaries in the parenchymal septa were measured as were surface densities of the airspaces and gas exchange capillaries. Absolute changes in these parameters were related to body mass. Three phases of development were identified. During the ectothermic period, in the first 70 days after birth when the lung was in the terminal air sac phase, the most marked change was an increase in volume density of septal interstitium. The transitional period between ectothermy and endothermy, between 70 and 180 days after birth, corresponded to the alveolar phase and was characterised by accelerated increase in air space surface area. Maturation of the parenchymal septa and establishment of the mature capillary system occurred largely after 180 days when endothermy was established. The anatomical diffusion factor in the tammar wallaby adult is similar to that for eutherians.

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A study of 15 childhood fatalities due to farm or tractor-related accidents demonstrated extensive injuries typified by crushing, evisceration, and amputation of limbs. Although these injuries are characteristic of industrial accidents in adults, such accidents do not commonly occur in children. However, the unique circumstance of the farm, which incorporates home and industrial environments, results in particularly severe patterns of injuries in accidental childhood deaths. A knowledge of the range of machines that are used and the environment of the farm facilitates assessment of the types of injuries that may be found at autopsy in cases of pediatric farm accident.

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Infants who are preambulatory and toddlers who have only just learned to walk have particular characteristics that give them a unique susceptibility to drowning in certain circumstances. A study of drowning deaths in 32 infants and children <2 years of age in South Australia over a 35-year period from March 1963 to February 1998 was undertaken. The age range was 3 to 24 months (average, 15.4 months), and there was a male:female ratio of 21:11. Drownings occurred in home swimming pools (N = 10); baths (N = 9); waterways (i.e., rivers, irrigation ditches, sea; N = 5); buckets, bins, sinks (N = 4); and fish ponds (N = 3). Details were lacking in one case. Two cases raised questions regarding the manner of death and the possibility of inflicted injury. Specific problems that occur in the assessment of infant drownings include the vulnerability of infants to accidental and nonaccidental drowning, the absence of autopsy findings in inflicted drowning, and the lack of independent witnesses to the fatal episodes. Although the numbers of childhood drownings have declined in recent years, specific situations that remain dangerous for infants include unsupervised bathing and access to swimming pools, fish ponds, and industrial buckets containing water. Complete submersion does not have to occur for drowning to take place.

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Postnatal growth of the lung in the tammar wallaby, Macropus eugenii, was investigated using morphometric techniques with light microscopy. Lung volume, parenchymal and non-parenchymal volume densities were measured. Volume densities of parenchymal airspace and tissue and non-parenchymal conducting airways and large blood vessels were determined. Lung volume and all the other parameters that were measured showed a biphasic increase in relation to increase in body mass. All parameters, with the exception of airway volume, increased relatively slowly in relation to increase in mass in the first 70 days after birth, when the pouch young are ectothermic. Between 70 and 180 days, during the period of transition from ectothermy to endothermy, the parameters increased more rapidly, suggesting accelerated lung growth in preparation for the extra metabolic demands associated with the establishment of thermoregulatory control in the pouch young. Specific lung volume in the adult tammar is lower than that of eutherians of equivalent mass, however, the parenchymal volume is relatively high.

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The incidence of congenital diaphragmatic hernia (CDH) is 1:1,207-5,000, and the condition is associated with high mortality and morbidity, attributed principally to associated pulmonary hypoplasia. Repairing the diaphragmatic defect by antenatal surgery has high mortality, mainly due to premature labor. Antenatal tracheal occlusion, which is achievable by less invasive methods, stimulates lung growth (weight and DNA). However, its effectiveness in reversing structural and maturational abnormalities and its optimal timing requires further investigation. We hypothesized that (1) antenatal tracheal occlusion performed in the lamb model of congenital diaphragmatic hernia will stimulate lung growth and structural development and restore lung structure and maturity toward normal levels by term gestation; (2) effects will be detectable by morphometric measurements of the following parameters: lung volume, ratio of parenchyma to nonparenchyma, volume density of connective tissue within nonparenchyma, ratio of gas exchange tissue to airspace in parenchyma, gas exchange surface area, capillary loading, alveolar/airspace density and alveolar perimeter; (3) effects will be seen in all lobes of the lung; and (4) a greater effect will be observed when tracheal occlusion is performed early rather than late in gestation. Fourteen lambs underwent CDH creation at gestation day 72-74 followed by tracheal occlusion at day 101 (n = 7) or 129 (n = 7). They were delivered by Cesarean section at 143 days (term = 145-149). Lungs were obtained at autopsy, inflation fixed, divided into lobes, and sampled; morphometric analysis was performed. Comparisons were made with previously reported results from control lungs of normal lambs and lambs with untreated CDH. In comparison with untreated lungs, antenatal tracheal occlusion at both times resulted in increased volumes for total lung and lobes, increased volume density of parenchyma and of airspace within parenchyma, and increased gas exchange surface areas. Normal values for gas exchange surface area density, and alveolar density and perimeter were attained and the lungs appeared more mature than non-occluded lungs. Tracheal occlusion earlier in gestation produced a greater effect, achieving greater than normal values for lung volumes and volume densities, whereas the capillary loading value was similar to normal lung. Later occlusion achieved less than normal values for lung volumes and volume densities, with a reduced capillary loading value. We conclude that antenatal tracheal occlusion is capable of reversing structural total lung and lobar hypoplasia and immaturity caused by CDH as determined by morphometrically determined parameters. The effect is greater when tracheal occlusion is performed early rather than late in gestation. The results are encouraging for development of treatment methods for humans with antenatally diagnosed CDH.

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OBJECTIVE: To analyse the circumstances surrounding farm and tractor-related childhood fatalities in South Australia, to identify potentially dangerous situations and to delineate prevention strategies. METHODS: A retrospective search of files was conducted at the Women's and Children's Hospital Department of Histopathology from 1981 to 1996, and the State Coroner's Office from 1988 to 1996. RESULTS: Fifteen fatalities were identified comprising 11 boys and four girls (age range, 2 years 11 months to 13 years; average, 6 years). Activities prior to death included riding on a tractor/trailer (n=8); playing near a field grain storage bin (n=2); playing near machinery (n=2); sleeping in a car near a burn off (n=1); walking around a dam (n=1) and riding as a passenger on a motorbike (n=1). Causes of death included multiple skull fractures and cerebral damage (n=11), asphyxia (n=2), drowning (n=1) and incineration (n=1). CONCLUSIONS: The most dangerous activity involved children riding unrestrained on tractors; falls resulted in extensive injuries from tractor rear wheels or towed machinery. Allowing children on farms to ride on tractors or machinery only if there is a safe seat with a restraining harness would substantially reduce the number of fatal farm-related childhood injuries in South Australia.

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The lung of the new-born marsupial is at the terminal air sac stage of development. The maturational status of the lung of new-born tammar wallaby was assessed using established morphometric techniques and the results were compared with data from a morphometric study of the lung of the rat. Volume densities of the parenchyma and non-parenchyma, conducting airways and blood vessels, the relative volumes of airspace and tissue, the thickness and the composition of the septa differed between the two species. In addition the volume of capillaries and the surface area of the effective gas-exchange tissue was greater in the new-born rat than in the new-born tammar pouch young. The lung of the new-born tammar appears to be at an earlier phase of the terminal air sac stage than that of the new-born rat. Lung development up to birth appears to be commensurate to the metabolic needs of the organism at birth.

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Congenital diaphragmatic hernia (CDH) in humans is relatively common and associated with high mortality attributed mainly to pulmonary hypoplasia. Previous animal models have induced CDH late in gestation, in contrast to the human situation, and only limited morphometric analyses have been reported. We undertook early surgical creation of CDH in fetal lambs, days 72-74 of gestation (n = 8), with unoperated lambs (n = 8) as controls. At 143 days (term = 145-149) a cesarean section was performed and the lungs were obtained, inflation fixed, divided into lobes, and processed for morphometry. In the CDH group the total lung volumes (51.3 mL compared to 223.8 mL) and gas exchange surface areas (5.85 m2 versus 26.43 m2) were less than one quarter of control values. Capillary loading was reduced from 0.3 mL/m2 in controls to 0.12 mL/m2 in CDH and parenchymal volume reduced from 77% in controls to 57% in CDH. Within parenchyma, gas exchange tissue volume was increased in CDH (66%) compared with controls (50%). CDH lungs had primitive air sacs/alveoli that were smaller (perimeter 83 microns) and more numerous (1321 per mm2) than in controls (perimeter 132 microns, 504 per mm2). The left lung and left upper lobe were affected most. Induction of CDH in the lamb at this early age results in quantifiable, reproducible pulmonary hypoplasia from which comparisons can be made with the human condition.

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PURPOSE: To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS: Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS: Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION: This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.

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Fetal lambs with diaphragmatic herniae (CDH) created surgically at 73 days' gestation were subjected to three different forms of intrauterine correction: silastic patch correction of the diaphragmatic defect plus an abdominal patch at 101 days gestation; an intrathoracic "silo" at 101 days; and a tracheal "plug" obstruction at 101 or 129 days. At 143 days' gestation (term 145-149 days), the lambs were delivered by caesarean section and ventilated for 30 min before undergoing respiratory compliance measurements. These results were compared to those of normal lambs and animals with uncorrected herniae. The total respiratory system compliance values in those groups undergoing corrections were remarkably similar: those with any form of correction had a significant improvement (P < 0.05) compared to those with herniae and no correction (patch = 1.57 = ± 0.182 ml/cm H2O; silo = 1.53 ± 0.179; plug at 101 days = 1.66 ± 0.311; plug at 129 days = 2.00 ± 0,175; without correction = 0.62 ± 0.073). None, however, reached the values of those with normal lungs: 2.72 ± 0.223 (P < 0.05). This improvement in compliance in all corrected groups suggests that fetal tracheal obstruction is as effective as the two more invasive forms of open fetal surgery carried out in this study and, as this procedure lends itself to surgery through a small uterine incision or "minimally invasive" surgery, it may be the procedure of choice to reduce the incidence of preterm labour for those human fetuses undergoing antenatal correction of a CDH.bb.