In vitro and in vivo analysis of the inability of fetal rabbit wounds to contract.

Fetal rabbit wounds that are sutured show excellent repair without obvious scarring. In contrast, an unsutured wound in a rabbit fetus does not close, and it appears that the process of wound contraction does not occur. Experiments were carried out to illustrate the mechanisms responsible for the noncontraction of open fetal rabbit wounds. Results showed that the lack of wound contraction was not an artifact caused by rapid fetal growth. With regard to the ability of cultured fetal fibroblasts to show cytoplasmic muscle-induced cell contraction, we found that, in cultured fetal fibroblasts, cell contraction was induced by adenosine triphosphate. Contractile abilities of fetal-derived fibroblasts were equivalent to those of adult-derived fibroblasts. The fetal fibroblasts also demonstrated the generation of superior contractile activity when examined in a fibroblast-populated collagen lattice model. Finally, the ability of amniotic fluid to alter wound contraction was addressed by means of the fibroblast-populated collagen lattice in vitro model. Increasing concentrations of amniotic fluid inhibited fetal fibroblast lattice contraction. Therefore, rabbit amniotic fluid contains an inhibitor that may be partially responsible for the noncontraction of fetal rabbit wounds in utero.

Characterization and quantitation of wound matrix in the fetal rabbit.

Fetal response to injury has been characterized by the deposition of a matrix that is not primarily collagen. This study was designed to identify this matrix, in order to better understand the fetal mechanism of tissue repair. Silastic/polyvinyl alcohol sponge (PVA) wound implants were placed paravertebrally in 24-day gestation (31 days = term) fetal (n = 65) and adult (n = 43) rabbits and then harvested from one hour to 6 days post-wounding. Histologic analysis of the fetal wound matrix deposited in the PVA implants suggested the presence of glycosaminoglycans (GAG) rather than the collagen found in adult wound implants. To further analyze the fetal wound matrix, the GAG content was quantitated using an Alcian Blue dye-binding assay. Results showed significantly increased (p less than 0.05) GAG deposition on days 2-6 in the fetal wound compared to the adult wound. Fetal GAG levels were approximately three times those of the adult during this period. Separation of individual GAG species by cellulose acetate electrophoresis demonstrated that the GAG matrix of the fetal wound was composed predominantly of hyaluronic acid. This finding was confirmed by selective enzymatic digestion of separated GAG species using highly specific polysaccharidases. These observations of hyaluronic acid deposition in the fetal wound may be ascribed an important physiologic role by providing a more fluid and malleable matrix rather than a restrictive matrix composed of collagen. This new evidence coupled with earlier findings of the lack of an acute inflammatory response in the fetus further supports the hypothesis that the fetal response to injury is significantly different from the adult response.

Transthoracic Nissen fundoplication for gastroesophageal reflux in patients with severe kypho-roto-scoliosis.

Transthoracic Nissen fundoplication was used for the correction of gastroesophageal reflux in five mentally retarded patients with severe kypho-roto-scoliosis. This deformity may result in a gastroesophageal junction so high above the left costal margin that transabdominal fundoplication is extremely difficult. Operative morbidity was minimal. One wrap disruption occurred that required reoperation. Results have been satisfactory 6 to 24 months postoperatively.

Twelve-year clinical experience with the Greenfield vena caval filter.

Optimal protection from pulmonary thromboembolism (PE) by a mechanical device requires long-term freedom from complications as well as from recurrent PE. From 1974 to 1986 the Greenfield filter was implanted surgically in 469 patients, most commonly when anticoagulation was contraindicated (38%) or failed to prevent recurrent PE (27%). The jugular vein was used for access in 83% and the femoral vein in 16%; in the remainder the filter was inserted via the right atrium or the left axillary vein. Technical complications included air embolism in 4 patients (0.9%) and misplacement in 19 (4%), with no sequelae. There were 7 deaths from PE within 48 hours postoperatively, primarily in patients with pulmonary hypertension. An additional 9 later deaths were attributed to PE, 5 confirmed by autopsy, but in only 1 of these was there trapped thrombus in the filter. An additional 9 patients had nonfatal PE, suspected and confirmed in 2 by angiogram, for an overall recurrent PE rate of 4% over 12 years. During this follow-up there were 133 deaths, and 146 patients were followed up for an average of 43 months (190 were lost to follow-up). Ten patients had thrombosed inferior venae cavae at the time of insertion of the Greenfield filter, and 3 were recanalized late to a caval patency rate of 96%. Three initially patent filters occluded, for a long-term filter patency rate of 98%, which was independent of anticoagulation. Clinically silent embolism into the Greenfield filter was seen in 18 patients, half of whom had dissolution on subsequent cavogram. Venous stasis sequelae developed in 44% of the patients, compared with 52% with preoperative edema, and ulceration was seen in 3%. Of 32 patients who had suprarenal filters, 11 died and 12 returned for follow-up study, which showed that all were patent. Favorable results with suprarenal filter placement have made this an appropriate choice in pregnant women and in young women anticipating pregnancy.

Transforming growth factor beta (TGF-beta) induces fibrosis in a fetal wound model.

The adult cellular response to tissue injury is characterized by acute inflammation followed eventually by fibroblast proliferation and collagen synthesis. Fetal tissue responses to injury differ markedly from those of the adult; an early acute inflammatory response is absent, few fibroblasts participate, and no collagen is deposited. The object of the present study was to analyze the effects of transforming growth factor beta (TGF-beta), an important regulatory molecule in adult healing events, on the fetal tissue response following wounding. Fetal cellular and extracellular matrix responses to injury were evaluated by placing subcutaneous wound implants containing TGF-beta (0.01 to 10 ng) in fetal rabbits at 24 days gestation (term = 31 days). Histologic responses one to seven days later were compared with fetal and adult control implants without TGF-beta. The histology of the adult implant was characterized by an early acute inflammatory response: by day 7 fibroblasts and collagen were predominant. In contrast, control implants removed from fetal rabbits had no histologic evidence of acute inflammation or fibroblast penetration and no collagen was deposited. When implants containing 1.0 ng TGF-beta were removed from fetal rabbits at seven days, a grossly fibrotic reaction was observed: histology confirmed marked fibroblast penetration with collagen deposition. Fetal implants containing 0.01 ng or 10 ng TGF-beta showed few fibroblasts but had increased numbers of inflammatory cells compared with controls. These observations demonstrate that the fetal response becomes adultlike with fibroblast proliferation and collagen accumulation when TGF-beta is added, thus documenting the responsiveness of the fetal system to adult repair signals.(ABSTRACT TRUNCATED AT 250 WORDS)

Cricoid split for subglottic stenosis in infancy.

Historically, tracheostomy has been used for infants with airway obstruction caused by congenital or acquired subglottic stenosis. Postoperative morbidity and mortality with this provisional operation led Cotton, in 1980, to substitute anterior cricoid split as the primary definitive procedure. Within the past three years, anterior cricoid split has been performed in 4 infants, aged 3 to 9 months, with acquired (3 patients) or congenital (1 patient) subglottic stenosis requiring ventilation through an endotracheal tube. Following cricoid split, the trachea is stented for 12 to 14 days by a nasotracheal tube, with extubation and rigid bronchoscopy in the operating room with the patient under anesthesia to confirm healing and patency. During an 18- to 24-month follow-up in these 4 patients, morbidity has been minimal, patency has persisted, and stridor has not recurred. Accordingly, a conclusive operation, cricoid split, rather than a temporizing tracheostomy may be employed for certain obstructive tracheal lesions early in life.

Multifocal ganglioneuroblastoma coexistent with total colonic aganglionosis.

Neuroblastoma and Hirschsprung's disease are considered aberrations of neural crest cell growth, migration, or differentiation. Their coexistence, however, is rare. We present the case of an only child with total colon Hirschsprung's disease diagnosed shortly after birth, who was found to have noncontiguous ganglioneuroblastomas without metastases at age 16 months. The spectrum of neural crest anomalies, long segment Hirschsprung's disease and multifocal neuroblastoma, in this child is unique and previously unreported.

Experimental comparison of percutaneous vena caval devices: titanium Greenfield filter versus bird's nest filter.

A venous embolism model with autogenous thrombus was used for comparison of the functional properties of two new vena caval devices: a titanium Greenfield filter and the bird's nest filter. All nine Greenfield filters were correctly placed in the inferior vena cava and produced significant clot lysis of 81.3% +/- 16.3% (p less than 0.001, paired t test). Difficulty was encountered in affixing the hooks of the bird's nest device into the vein wall and resulted in two filters not being inserted and two filters being placed too proximally. One set of hooked wires of another bird's nest device migrated to the right atrium despite correct insertion. Eight bird's nest devices allowed clot lysis of 83.4% +/- 17.7% (p less than 0.001), paired t test) but thrombus size was increased in one case. The Greenfield and bird's nest filters have comparable effects on trapped emboli, but the bird's nest filter may be susceptible to thrombosis and occlusion under certain circumstances. The pre-shaped hooked wires of the bird's nest device may be difficult to insert and may allow proximal migration after a large thrombus was trapped.