Publikationen

In a previous series of fetal sheep experiments, the authors demonstrated that midgestational exposure of the normal spinal cord to the amniotic space leads to a myelomeningocele (MMC) at birth that closely resembles human MMC phenotypes in terms of morphology and functional deficit. The present study tested whether delayed in utero repair of such evolving experimental MMC lesions spares neurological function. In 12 sheep fetuses, a spina bifida-type lesion with exposure of the lumbar spinal cord was created at 75 days' gestation (full term, 150 days). Four weeks later, the developing MMC lesions were repaired in utero for seven fetuses (five fetuses died before this time). Of those that had repair, three were delivered near term by cesarean section, and four died in utero or were aborted. All survivors had healed skin wounds and near-normal neurological function. Despite mild paraparesis, they were able to stand, walk, and perform demanding motor tests. Sensory function of the hindlimbs was present clinically and confirmed electrophysiologically. No signs of incontinence were detected. Histologically, the exposed and then covered spinal cord showed significant deformation, but the anatomic hallmarks as well as the cytoarchitecture of the spinal cord essentially were preserved. These findings show that timely in utero repair of developing experimental MMC stops the otherwise ongoing process of spinal cord destruction and “rescues” neurological function by the time of birth. Because there is evidence that a similar secondary damage to the exposed neural tissue also occurs in human MMC, we propose that in utero repair of selected human fetuses might reduce the neurological disaster commonly encountered after birth.

Journal: Journal of Pediatric Surgery (Volume 31, Issue 3, Pages 397-402)

Experimental fetal neurosurgery: the normal neurology of neonatal lambs and abnormal findings after in utero manipulation

No abstract available

Journal: Contemporary Topics in Laboratory Animal Science 1996 Jan;35(1):53-6

Fetal reconstructive surgery: experimental use of the latissimus dorsi flap to correct myelomeningocele in utero

A recent study in human fetuses with myelomeningocele produced evidence that nonclosure of the spine leads to progressive damage of the exposed spinal cord during pregnancy. Thus in utero coverage might spare function. We tested the use of the latissimus dorsi flap for fetal myelomeningocele repair. In seven sheep fetuses, a lumbar myelomeningocele type of lesion was created at 75 days' gestation and was covered with a "reversed" latissimus dorsi flap at 100 days. At term, the three survivors had healed cutaneous wounds and normal hindlimb function. The vascular pedicle of the latissimus dorsi flap was patent, the viable flap covered the entire lesion, and the underlying spinal cord was grossly intact. We conclude that the latissimus dorsi flap repair is suitable for fetal surgery and provides efficient coverage of the lesion. These results have clinical implications, since fetal myelomeningocele repair may be a compelling way to reduce the severe neurologic deficit in humans.

Journal: Plastic and reconstructive surgery 1995 Oct;96(5):1007-11

Exogenous transforming growth factor-beta amplifies its own expression and induces scar formation in a model of human fetal skin repair.

etal skin wounds heal without scarring. To determine the role of TGF-beta 1 in fetal wound healing, mRNA expression of TGF-beta 1 was analyzed in human fetal and adult skin wounds.

Journal: PubMed

Fetal skin wounds heal without scarring. To determine the role of TGF-beta 1 in fetal wound healing, mRNA expression of TGF-beta 1 was analyzed in human fetal and adult skin wounds.

Journal: Annals of Surgery (Vol. 222, No. 2, 146-154)