Biomedical subjects

M Meuli

Publications and source records attributed to M Meuli.

At least 19 recordsLinked to original sources

PubMed2001

Prenatal diagnosis of a fetus with lumbar myelocystocele.

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.

Adult↗

PubMed2001

Efficient gene expression in skin wound sites following local plasmid injection.

Transfection of the skin by local gene delivery, as well as widespread transfection of systemic tissues following intravenous injection of cationic liposome/DNA complexes have been reported. Here, we show that surgically wounded mouse skin can be transfected either by local injection of DNA alone or by intravenous injection of optimized cationic liposome/DNA complexes; however, direct cutaneous injection produces much higher levels of gene expression in the skin, which is targeted to dermal and subdermal layers. High levels of chloramphenicol acetyltransferase activity were present from 3 h to 2 wk following direct injection of a gene expression plasmid into wounded skin and were maintained at detectable levels up to 8 wk after injection. Expression of transferred chloramphenicol acetyltransferase as well as beta-GAL genes was localized to fibroblasts, macrophages, and adipocytes as determined by histochemistry and immunohistochemistry. Further- more, local injection of a human granulocyte- colony-stimulating factor gene expression plasmid produced high levels of the biologically relevant human granulocyte-colony-stimulating factor protein in wounded mouse skin. This efficient and simple method of site-specific gene transfer into wounds may lead to the development of cutaneous gene therapy directed against disorders of abnormal cutaneous wound healing.

Animals↗

PubMed2001

Fractures of the neck of the radius in children. Early experience with intramedullary pinning.

The treatment of fractures of the neck of the radius in children is difficult, particularly if the angulation of the fracture exceeds 60 degrees. Since 1994 we have used closed reduction and stabilisation with an intramedullary Kirschner wire in patients with grade-IV fractures according to the classification of Judet et al. In a retrospective analysis of a two-year period (1994 to 1996), 324 children with fractures of the elbow were treated in our department. Of these, 29 (9%) had a fracture of the neck of the radius; six were grade-IV injuries (1.9%). Five of the latter had an excellent postoperative result with normal movement of the elbow and forearm. One patient with a poor result had a concomitant dislocation of the elbow. Our results suggest that closed reduction and intramedullary pinning of grade-IV fractures allows adequate stabilisation while healing occurs.

Bone Nails↗

PubMed2000

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

Fetal skin wounds heal scarlessly while adult wounds scar. Fetal wound healing occurs in a physiologically hypoxic environment whereas in adult wound healing, cells have to acutely adapt to hypoxia caused by locally impaired blood supply. We examined the expression of hypoxia-inducible factor 1 (HIF-1), a potent transcriptional regulator of oxygen-dependent genes such as vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-beta), a potentially HIF-1-regulated scarring cytokine, on fetal and adult responses to wounding. Incisional skin wounds were created in four sheep fetuses (twins served as controls) and two ewes at 100 days of gestation (term = 150 days). Fetal and adult wounds as well as non-wounded control tissues were harvested 2 days post-wounding. Intraoperative arterial blood gas analyses and invasive subcutaneous pO2 measurements revealed that the fetuses were indeed hypoxic while the mothers were normoxic. Expression patterns of HIF-1alpha were investigated by Western blot analyses. HIF-1alpha expression in fetal wounds and fetal control skin was similar, whereas HIF-1alpha was only detected in adult wounds but not in adult control skin. Exposure of cultured fetal and adult dermal fibroblasts to hypoxia (1% O2) showed a marked induction of VEGF mRNA. In contrast, exposure of these cell types to hypoxia did not significantly affect TGF-beta1 mRNA expression in comparison to their normoxic controls. The presence of HIF-1alpha in fetal but not in adult normal skin indicates that HIF-1alpha might be involved in fetal skin development. Conversely, the upregulation of HIF-1alpha in adult but not early fetal wound repair might represent a pathway in the pathogenesis of scarring, since several growth factors overexpressed in, and associated, with scarring are hypoxia-inducible. Further studies need to be performed in order to identify hypoxia-regulated HIF-1alpha target genes involved in the pathogenesis of scarring.

Age Factors↗

PubMed2000

A toddler with burns, stomatitis, and skin graft loss.

The authors report on a healthy 21-month-old toddler with 13% TBSA deep scald burns who was successfully grafted (take 100%). In the immediate postoperative phase, the patient developed classical aphthous stomatitis and subsequent herpes viremia leading to severe viral "graftitis". Although immediately administered intravenous acyclovir therapy appeared to be effective, one third of grafts were lost and had to be replaced. The lesson from this case is 2-fold: Herpes infection may threaten even perfectly engrafted fresh skin transplants, and, freshly grafted or soon to be grafted burn patients should be given intravenous antiviral therapy as soon as a herpes infection is diagnosed.

Antiviral Agents↗

PubMed2000

Psychological long-term adjustment in children with head burns.

OBJECTIVE: To determine psychological adjustment of children after head burns. METHODS: One hundred four children and adolescents between the ages of 5 and 17 years were assessed with the Child Behavior Checklist 1 to 13 years after burn. Mean total body surface area burned was 18%. According to burn localization, patients were classified into two groups: patients with head burns versus patients with burns of other areas. RESULTS: Psychological adjustment as measured by the broad- and narrow-band scales of the Child Behavior Checklist was normal in both samples of burned patients. CONCLUSION: This study failed to find any specific psychological problems in survivors of pediatric head burns.

Adaptation, Psychological↗

PubMed2000

Genetically modified mouse models in studies on cutaneous wound healing.

Genetically modified mice have become an invaluable tool in modern biomedical and basic research. This review provides an overview of knockout and transgenic mice studied with regard to their cutaneous wound healing properties. In addition, several gene transfer studies are briefly introduced, which have further highlighted our knowledge on individual gene function in wound healing.

Animals↗

PubMed1999

Gene expression along the cerebral-spinal axis after regional gene delivery.

We demonstrate here that intracerebroventricular or spinal cord (intrathecal) injection of either plasmid DNA alone or cationic liposome: DNA complexes (CLDCs) produces significant levels of expression of both reporter genes and biologically relevant genes in nonparenchymal cells lining both the brain and the spinal cord. Gene expression was identified both within the spinal cord and the brain after intracerebroventricular or intrathecal injection of either CLDCs or plasmid DNA alone. Intracerebroventricular or intrathecal injection of CLDCs containing the beta-galactosidase (beta-Gal) gene produced patchy, widely scattered areas of beta-Gal expression. The chloramphenicol acetyltransferase (CAT) reporter gene product reached peak levels between 24 hr and 1 week postinjection, and was still present at significant levels 3 weeks after a single intracerebroventricular or intrathecal injection. Intrathecal injection of the human granulocyte colony-stimulating factor (G-CSF) gene produced high levels of hG-CSF activity in both the spinal cord and the brain. Intracerebroventricular injection of CLDCs containing the murine nerve growth factor (NGF) gene increased mNGF levels in the hippocampus, a target region for cholinergic neurons in the medial septum, and increased cholinergic neurotransmitter synthetic enzyme choline acetyltransferase (ChAT) activity within the brain, a well-characterized effect of both purified and recombinant NGF protein. These findings indicate that intracerebroventricular or intrathecal injection of CLDCs can produce significant levels of expression of biologically and therapeutically relevant genes within the CNS. Efficient gene transfer into the CNS will facilitate the evaluation of gene function and regulation within the brain and spinal cord. We attempted to transfer and express genes within the brain and spinal cord by direct CNS injection of either DNA alone or CLDCs into the intraventricular and subarachnoid compartments. We show that intracerebroventricular or spinal cord (intrathecal) injection of either plasmid DNA alone or CLDCs produces significant levels of expression of both reporter genes and biologically relevant genes in nonparenchymal cells lining both the brain and the spinal cord. Intrathecal injection of the hG-CSF gene produced high levels of hG-CSF activity in both the spinal cord and the brain. Intracerebroventricular injection of CLDCs containing the murine NGF gene increased mNGF levels in the hippocampus, and increased cholinergic neurotransmitter synthetic enzyme ChAT activity within the brain. Locoregional diffusion of gene products expressed by transfected meningeal lining cells into brain and spinal cord parenchyma could potentially target secreted proteins within brain and spinal cord regions relevant to neuropathological states while limiting peripheral side effects.

Animals↗

PubMed1999

Assessment of sensory function in neonatal sheep with somatosensory evoked potentials: methodology and normative data.

Fetal sheep are increasingly used as animal models for fetal surgical interventions such as repair of myelomeningocele. Since behavioral observations cannot provide objective information about preservation of sensory function, we have developed a technique for reliably recording somatosensory evoked potentials in neonatal sheep. We determined anatomic criteria for placement of recording electrodes over the somatosensory cortex using external landmarks, and recorded normative data for both ulnar and posterior tibial nerve stimulation in a series of normal neonatal sheep. The methodology and normative data are presented in this report; a companion paper demonstrates the utilization of this technique in a variety of experimental fetal interventions.

Animals↗

PubMed1999

Experimental fetal neurosurgery: effects of in-utero manipulations on somatosensory evoked potentials.

Somatosensory evoked potentials (SEP) were used to objectively evaluate sensory function in neonatal sheep after experimental fetal surgery. Posterior tibial (PTN) and ulnar (UN) nerves were stimulated electrically and averaged SEP were recorded from scalp electrodes placed over the somatosensory cortex. Animals with experimentally-created myelomeningocele (MMC) showed no SEP to PTN stimulation, but normal SEP to UN stimulation. In-utero repair of the MMC resulted in preservation of neurologic function and normal PTN SEP. In-utero thoracic spinal-cord transection resulted in no regeneration, and no SEP to PTN stimulation. In-utero unilateral transection of the sciatic nerve, even with attempted repair, resulted in little or no regeneration and absent or grossly abnormal PTN SEP from the affected side. In summary, the SEP technique provides valuable information concerning preservation of sensory function in a variety of experimentally created neurologic abnormalities and can aid in functional evaluation of experimental therapeutic fetal interventions.

Animals↗

PubMed1999

Confocal laser scanning analysis of the association of fibulin-2 with fibrillin-1 and fibronectin define different stages of skin regeneration.

The fibulins represent a novel family of extracellular matrix proteins. We report the temporo-spatial expression of fibulin-2 in skin regenerating from keratinocyte autografts. In normal dermis, fibulin-2 was associated with the fibrillin-containing microfibrillar apparatus, except for the portion immediately adjacent to the dermo-epidermal junction. In contrast, early regenerating dermis showed numerous fusiform fibrillin-microfibrils along the basement membrane, whereas fibulin-2 was present in a distinct and separate layer below. Both proteins formed independent fibrillar systems also in the reticular dermis without significant colocalization; however, over time both fibril systems became congruent: after 4 mo there was extensive colocalization of fibulin-2/fibrillin in the reticular dermis, after 17 and 24 mo this also occurred in the papillary dermis. Simultaneous visualization of fibulin-2 and fibronectin revealed an inverse pattern: complete colocalization at 7 d and discordant distribution 17-24 mo after grafting. In particular, the fibrillar fibronectin pattern at early time points changed into a faint granular distribution throughout the dermis and along the subbasement membrane region as in normal skin. Dermal fibroblast cultures showed that fibrillin and fibronectin participated in distinct fibrillar systems; however, fibulin-2 colocalized with either protein. We propose that, in regenerating skin, fibulin-2 is a late component of the cutaneous microfibrillar apparatus with an earlier existence in a fibrillar matrix mediated by fibronectin. This suggests interaction of fibulin-2 with both fibronectin fibrils and fibrillin microfibrils, and is consistent with in vitro binding data.

Adult↗

PubMed1998

The cutaneous microfibrillar apparatus contains latent transforming growth factor-beta binding protein-1 (LTBP-1) and is a repository for latent TGF-beta1.

The transforming growth factors-beta1 and beta2 (TGF-beta) stimulate synthesis of extracellular matrix proteins in vitro and appear upregulated in fibrotic conditions, in scar formation, and in wound healing. The extracellular matrix in turn might also act as a scavenger or repository for TGF-beta. We therefore studied the in situ distribution of latent TGF binding protein-1 (LTBP-1) and latent TGF-beta1 on extracellular matrix elements of normal human skin and skin regenerating from cultured keratinocyte autografts. We localized both LTBP-1 and latent TGF-beta1 to fibrillin-containing (elastic) microfibrils. Both LTBP-1 and latent TGF-beta1 were already present during the earliest stages of the de novo formation of the microfibrillar apparatus, i.e., on fusiform, randomly oriented microfibrils that later coalesced to form the typical candelabra-like structures in the papillary dermis. We show herewith that LTBP-1 exerts a dual role as a component of fibrillin-microfibrils of the skin and in targeting latent TGF-beta1 to the cutaneous microfibrillar apparatus. Thus, this major connective tissue structure does not only serve as a force bearing element and scaffold for elastin deposition in the dermis, but also as an important repository for latent TGF-beta in the skin.

Adult↗

PubMed1998

Altered smooth muscle development and innervation in the lower genitourinary and gastrointestinal tract of the male human fetus with myelomeningocele.

PURPOSE: We determine whether smooth and skeletal muscle or nerve density is altered in the lower genitourinary or gastrointestinal tract of male human fetuses with myelomeningocele at 20 weeks of gestation. MATERIALS AND METHODS: We serially cross sectioned the lower genitourinary and gastrointestinal tracts in 7 male fetuses (mean age 20 weeks of gestation) with myelomeningocele and 4 age matched controls. Immunohistochemical staining was performed using Masson's trichrome stain and antibodies to smooth and skeletal muscle actin. S-100 protein staining for Schwann cell localization and neurofilament protein was also done. Fluorescein and rhodamine double immunolabeling was used to demonstrate the co-expression of smooth and skeletal muscle. RESULTS: Peripheral neural innervation of the bladder, prostate and rectum was markedly decreased in myelomeningocele. Masson's trichrome and smooth muscle actin staining also demonstrated that smooth muscle was less well differentiated in myelomeningocele specimens. Scant smooth muscle was present in the myelomeningocele bladder and bladder neck with an excess of collagen in an interfascicular and intrafascicular distribution. Double immunofluorescence staining revealed persistent co-expression of smooth and skeletal muscle actin by myocytes in the myelomeningocele detrusor, while in the control bladder there was only smooth muscle expression. The skeletal muscle component of structures in fetuses with myelomeningocele, including the external sphincter, was similar to that in controls. Prostatic size, ductal morphogenesis and smooth muscle were decreased compared to those in controls. CONCLUSIONS: A global defect exists in the development of smooth muscle in myelomeningocele in the lower genitourinary and gastrointestinal tracts by 20 weeks of gestation. Peripheral nerve density is decreased in smooth muscle in myelomeningocele, suggesting that an intact nervous system is important for the development of normal smooth muscle. Fetal surgery with coverage of the spinal cord in select cases may prevent progressive environmental injury to the somatic nervous system during the second half of gestation. However, achieving normal autonomic function is unlikely due to the extent of early global organ maldevelopment.

Digestive System↗

PubMed1998

Spontaneous repair of superficial defects in articular cartilage in a fetal lamb model.

A fetal lamb model was developed to investigate the capacity of fetal articular cartilage for repair after the creation of a superficial defect. Superficial defects, 100 micrometers deep, were made in the articular cartilage of the trochlear groove in the distal aspect of the femur in eighteen fetal lambs that were halfway through the 145-day gestational period; the contralateral limb was used as a sham control. The wounds were allowed to heal in utero for three, seven, fourteen, twenty-one, or twenty-eight days. Seven days after the injury, the defects were filled with a hypocellular matrix, which stained lightly with safranin O. At twenty-eight days, the staining of the matrix was similar to that of the sham controls and the chondrocyte density and the architectural arrangement of the cell layers had been restored. An inflammatory response was not elicited, and no fibrous scar tissue was observed.

Animals↗

PubMed1997

Burns (Part 2). Tops and flops using cultured epithelial autografts in children.

The goal of this article is to review the status of cultured epithelial autografts in clinical practice with particular focus on the pediatric subset of patients. The current indications include massive deep burns (>60 - 70% total body surface area), resurfacing-type postburn scar revisions, and skin defect coverage following excision of large skin lesions like giant nevi. Although this method can be lifesaving for massively burned patients, and although excellent functional and cosmetic results may be obtained under ideal circumstances, formidable problems continue to exist. Take is inconsistent, cultured grafts are extremely susceptible to infection, and skin breakdown during the first months post grafting may occur due to mechanical instability of the regenerating skin. It may take one more decade of concerted research, jointly performed by clinicians and tissue culture technology experts in order to fabricate more skin-like grafts which are robust, reliable, and less expensive. Then, "cultured skin" will conquer the world and benefit countless patients.

Burns↗

PubMed1997

Cultured epithelial autografts: diving from surgery into matrix biology.

Cultured epithelial autografts offer an exciting approach to cover extensive skin wounds. The main problem of this method is mechanical instability during the first weeks after grafting. There is evidence that the shortcomings of autografting cultured keratinocytes result from the lack of a mature and functional dermo-epidermal junction. This article summarizes the current knowledge regarding the de novo formation of the dermo-epidermal junction and the dynamics of "take" and stabilization of cultured epithelial autografts. Future strategies are discussed of how to improve and accelerate the process conferring definitive stabilization of cultured epithelial autografts including the potential therapeutic use of transglutaminase as well as cocultivation of a dermo-epidermal equivalent in order to facilitate a permanent skin replacement.

Burns↗

PubMed1997

Scar wars: implications of fetal wound healing for the pediatric burn patient.

Scar formation and fibrosis often cause devastating disabilities in children suffering severe burn injury. In contrast to the child, the fetus has the ability to heal skin injury without scar formation, and instead with regeneration of epithelial and mesenchymal tissues and restoration of normal skin architecture. In this paper we review those unique features of the fetus and fetal wound healing that may contribute to the scarless repair process. It is hoped that an understanding of these remarkable reparative capabilities may lead to the development of new wound healing therapies that reduce or prevent scar formation and fibrosis in the management of children with burns.

Burns↗

PubMed1997

The spinal cord lesion in human fetuses with myelomeningocele: implications for fetal surgery.

Recently produced experimental evidence suggests that secondary traumatic injury and degenerative changes, acquired in utero, to the openly exposed neural tissue may be primarily responsible for the massive neurological deficit associated with myelomeningocele (MMC). The goal of this study was to examine the morphology of human fetuses with MMC to determine if acquired trauma to the spinal cord could be identified. The MMC lesions with surrounding tissues from 10 human fetuses ranging in gestational age between 19 and 23 weeks were prepared with serial histological sections. The MMC lesions were characterized by an open vertebral arch, an open dura mater fused laterally to the dermis, and an open pia mater fused laterally to the epidermis. The spinal cord was exposed, without any meningeal, bony, or cutaneous covering, and was resting on the dorsal aspect of the abnormal arachnoid sac created by the fusion of the meninges to the cutaneous tissues. The exposed neural tissue had undergone varying degrees of recent traumatic injury as a result of its exposed position, ranging from nearly complete preservation of neural elements in four cases to nearly complete loss in two cases. The neural tissue remaining in the MMC with partial loss contained hemorrhages and abrasions from recent injury, suggesting that injury occurred during passage through the birth canal. The presence of dorsal and ventral parts of the cord with nerve roots and ganglia demonstrated that these structures had formed during development and that the loss of tissue by injury was a secondary change. The results support the concept that performing in utero surgery could protect the exposed but initially well-developed and uninjured cord, prevent secondary neural injury, and preserve neural function in the human fetus with myelomeningocele.

Brain Damage, Chronic↗