Publikationen

Physiologically low oxygen concentrations in fetal skin regulate hypoxia-inducible factor 1 and transforming growth factor-beta3.

Annette Scheid1, Roland H Wenger1,Leonhard Schäffer1,Isabelle Camenisch1,Oliver Distler1, Andrej Ferenc1, Heidi Cristina1, Heather E Ryan1, Randall S Johnson1, Klaus F Wagner1, Urs G Stauffer1, Christian Bauer1, Max Gassmann1, Martin Meuli1

In the first-trimester mammalian fetus, skin wounds heal with perfect reconstitution of the dermal architecture without scar formation. Understanding environmental molecular regulation in fetal wound healing may reveal scar-limiting therapeutical strategies for the prevention of postnatal scarring wound repair. Therefore, we performed studies on fetal skin oxygenation and skin and wound expression of hypoxia-inducible factor 1alpha (HIF-1alpha) in the sheep model in vivo and performed studies on the potential relevance of HIF-1alpha during wound healing in vitro. Skin oxygen partial pressure levels were hypoxic throughout normal development. In nonscarring fetal skin at gestation day (GD)60, HIF-1alpha could be detected neither in healthy nor in wounded tissue. At GD100, in wounds with minimal scar formation, HIF-1alpha was expressed in fibroblasts and was markedly up-regulated at the wound edge. In scarring fetal wounds at GD120, HIF-1alpha was predominantly expressed in inflammatory cells. Expression of transforming growth factor beta3 (TGF-beta3), a potent antiscarring cytokine, overlapped with HIF-1a expression at GD100. HIF-1alpha-deficient mouse embryonic fibroblasts showed impaired migratory capabilities and demonstrated that TGF-beta3, but not proscarring TGF-beta1, manifests hypoxia- and HIF-1alpha-dependent regulation. In conclusion, HIF-1alpha-dependent regulation of a potent antiscarring cytokine may provide new strategies for antiscarring manipulation of wound healing.

Journal: PubMed

Date: 20/02/2003

Department of Surgery, University Children's Hospital of Zürich, Switzerland. ascheid@physiol.unizh.ch

Fetal Surgery for Myelomeningocele: Panacea or Peril?

Shinjiro Hirose  1 , Claudia Meuli-Simmen, Martin Meuli

Myelomeningocele affects thousands of children worldwide with devastating consequences. In an effort to improve neurologic outcome, fetal surgery has been performed for myelomeningocele for the past 5 years. Sensorimotor function is not appreciably improved, although there may be a reduction in hindbrain herniation and a decreased need for ventriculoperitoneal shunting. The long-term clinical consequences of these findings are not clear. What is clear, however, is that further study in the form of a prospective, randomized trial is mandatory.

Journal: World Journal of Surgery - published online: December 19, 2002

Date: 06/01/2003

1 The Fetal Treatment Center, Department of Surgery, Division of Pediatric Surgery, University of California, San Francisco, 513 Parnassus Avenue, Room HSW 1601, San Francisco, California 94143-0570, USA.

Hypoxia-regulated gene expression in fetal wound regeneration and adult wound repair

A Scheid1, R H Wenger1, H Christina1, I Camenisch1, A Ferenc1, U G Stauffer1, M Gassmann1, M Meuli1

Journal: PubMed

Date: 01/05/2002

1Department of Surgery, University Children's Hospital Zurich, Switzerland.

Prenatal diagnosis of a fetus with lumbar myelocystocele

N Kölble  1 , T A Huisman, T Stallmach, M Meuli, F Zen Ruffinen Imahorn, R Zimmermann

We present a case of a fetal lumbar myelocystocele, a rare congenital malformation, characterized by herniation of the central canal through a bony spina bifida. Routine ultrasound examination at 11 weeks' gestation by the primary obstetrician showed a suspicious cyst on the fetal back. Initially, the suspected diagnosis was a meningocele. After sonographic detection of newly developed fetal brain anomalies at 22 weeks' gestation the patient was referred to us. The enlarged cyst, which floated freely in the amniotic fluid, had a funnel-like appearance and was covered by a very thin layer of skin. With the help of ultrafast fetal magnetic resonance imaging the diagnosis of a fetal myelocystocele was made.

Journal: Ultrasound in Obstetrics & Gynecology (Volume 18, Issue 5, Pages 536-539)

Date: 01/11/2001

1 Unit of Perinatal Physiology, Department of Obstetrics, University Hospital, Zurich, Switzerland. nicole.koelble@fhk.usz.ch

The Fetus with a Myelomeningocele (in: The Unborn Patient: The Art and Science of Fetal Therapy. 3rd ed. 2001, chapter 28:443-452. Authors: Michael R. Harrison, Mark I. Evans, N. Sc. Adzick. ISBN: 0-7216-8446-7)

Meuli M.

This popular reference returns in the 3rd Edition with an exciting new focus entirely committed to fetal therapy. Leading authorities from around the world provide comprehensive management strategies for several dozen diseases that can now be detected in utero. Each disease is covered in its own chapter providing all of the exciting new options in prenatal and postnatal treatment. Coverage includes updated information on pathophysiology and the technical aspects of treatment. This content also provides excellent teaching material for families considering or undergoing treatment.

Journal: Saunders: The Unborn Patient

Date: 01/01/2001