Biomedical subjects

M Meuli

Publications and source records attributed to M Meuli.

At least 37 records · Page 2Linked to original sources

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↗

PubMed1997

Latissimus dorsi flap procedures to cover myelomeningocele in utero: a feasibility study in human fetuses.

There is experimental and clinical evidence that in utero repair of myelomeningocele (MMC) may preserve neurological function. In five aborted human fetuses (gestational age, 18 to 29 weeks), the authors tested whether proximally and distally based latissimus dorsi flaps (LDF) can be used to cover MMC lesions. Fetal soft tissues were developed enough to allow surgical handling, preparation of both flap types was technically easy, and the vascular pedicles could be preserved. The proximally pedicled LDF was suitable to cover the upper spine from lower cervical to lower thoracic levels, whereas the distally pedicled LDF was suitable to cover the spine between lower thoracic and lower sacral levels. These results suggest that various LDF procedures are technically feasible in early gestational human fetuses and could be used for in utero repair of MMC.

Back↗

PubMed1997

Efficacy of cultured epithelial autografts in pediatric burns and reconstructive surgery.

BACKGROUND: Cultured epithelial autografts are regularly used in burn patients, but they have not been tested in patients undergoing reconstructive surgery. The aim of this study was to analyze and compare the efficacy of cultured grafts in both burn and reconstructive surgery patients. METHODS: In six children with severe and massive burns, full-thickness areas were grafted with cultured grafts. In another six children with hypertrophic or hyperpigmented scars, or both, cultured grafts were used to cover defects resulting from scar excision or deep dermabrasion. RESULTS: In burn surgery the final cover rate averaged 60% (range, 0% to 100%). The functional and cosmetic results were good and at least equivalent to results after conventional grafting. Fragility, infection, and, in particular, mechanical instability of cultured grafts during the first weeks after transplantation were the main problems encountered. In reconstructive surgery the final cover rate was 100% in all patients. The functional and cosmetic results were very good and considered better than those obtained by using conventional grafting techniques. No major management problems were encountered. CONCLUSIONS: In massively burned children, cultured epithelial autografts represent an effective additional and potentially lifesaving method to conventional grafting. Questions remain regarding the use of this technique to treat less severe burns. For resurfacing-type scar revisions, cultured epithelial autografts yield excellent results that appear to be superior to those of conventional techniques.

Adolescent↗

PubMed1997

Laparoscopic removal of hydrosalpinx in a girl: case report.

We report on a 12-year-old girl who underwent laparoscopic excision of a left-sided hydrosalpinx. She presented with recurrent lower abdominal pain 8 years after appendectomy and resection of the left ovary. Sonography revealed a large cystic, tubular mass cranial and to the left of the urinary bladder. Laparoscopy demonstrated a left-sided hydrosalpinx which was resected endoscopically using a stapler.

Appendectomy↗

PubMed1997

Midgestational sciatic nerve transection in fetal sheep results in absent nerve regeneration and neurogenic muscle atrophy.

In order to test whether fetal nerve healing and regeneration result in complete functional recovery, we transected the sciatic nerve at trunk level in 13 midgestational sheep fetuses. In 10 fetuses immediate microsurgical nerve coaptation was performed. The neonatal lambs were evaluated clinically, electrophysiologically, and histologically. On the transected side, the 10 surviving lambs showed a sensorimotor sciatic nerve paralysis and atrophy of the muscles innervated by the sciatic nerve. Somatosensory evoked potentials were weakly present in 5 animals and absent in 5 animals. Histologically, minimal signs of axonal regeneration, massive degeneration of the entire nerve, and a marked neurogenic muscle atrophy were found. These unexpected results differ from the findings after peripheral nerve transections in late gestational sheep fetuses and also from the classic wallerian degeneration-regeneration pattern that follows adult nerve injury. We speculate that the almost absent regenerative potential at midgestation is related to axotomy-induced neurotrophic factor deprivation during a developmental phase where the neurons are critically dependent on growth factor for survival.

Animals↗

PubMed1996

Cross-linking of the dermo-epidermal junction of skin regenerating from keratinocyte autografts. Anchoring fibrils are a target for tissue transglutaminase.

Since transglutaminases create covalent gamma-glutamyl-epsilon-lysine cross-links between extracellular matrix proteins they are prime candidates for stabilizing tissue during wound healing. Therefore, we studied the temporo-spatial expression of transglutaminase activity in skin regenerating from cultured epithelial autografts in severely burned children by the specific incorporation of monodansylcadaverine into cryostat sections from skin biopsies obtained between 5 d to 17 mo after grafting. The dansyl label was subsequently immunolocalized in the epidermis, dermal connective tissue, and along the basement membrane. Incubation of cryosections of normal and regenerating skin with purified tissue transglutaminase confirmed the dermo-epidermal junction and the papillary dermis as targets for this enzyme and revealed that in regenerating skin transamidation of the basement membrane zone was completed only 4-5 mo after grafting. Immunoelectron microscopy revealed that three distinct regions on the central portion of anchoring fibrils were positive for monodansylcadaverine in normal skin which were negative during the initial phase of de novo formation of anchoring fibrils in regenerating skin. Biochemically, we identified collagen VII as potential substrate for tissue transglutaminase. Thus, tissue transglutaminase appears to play an important role not only in cross-linking of the papillary dermis but also of the dermo-epidermal junction in particular.

Adolescent↗

PubMed1996

Experimental fetal transesophageal and intracardiac echocardiography utilizing intravascular ultrasound technology.

Fetal transesophageal and intracardiac echocardiography by utilizing ultrasound technology permits accurate definition of cardiac anatomy in fetal sheep. Because fetal transesophageal echocardiography is less invasive than intracardiac echocardiography, it has the potential to serve as a monitoring tool for currently developed open and fetoscopic fetal cardiac interventions.

Animals↗

PubMed1996

Fetal endoscopic ('Fetendo') tracheal clip.

Fetal surgery can correct several life-threatening malformations before birth. Despite recent advances in fetal surgery, preterm labor remains a major problem directly related to the large uterine incision required for fetal exposure. Fetal endoscopic surgery ("Fetendo") obviates the need for a large uterine incision and may reduce the overall risks of fetal surgery by causing less uterine trauma and ultimately less preterm labor. Temporary tracheal occlusion is a promising strategy to enlarge the lungs in fetuses with congenital diaphragmatic hernia. Using the technology developed for laparoscopic surgery and for temporary tracheal occlusion, we have developed an endoscopic technique for tracheal occlusion with an endoscopic clip in a fetal sheep model. The evolution of this technique may allow temporary tracheal occlusion without incisional hysterotomy or maternal laparotomy.

Animals↗

PubMed1996

Immediate reconstruction for penile agenesis.

The goal of treatment for penile agenesis is early female gender assignment and feminizing reconstruction of the perineum. Historically, this required multiple operations including both vesicostomy and colostomy. The present case demonstrates the feasibility of early total reconstruction through a posterior sagittal approach that avoids diversion of stool and urine.

Congenital Abnormalities↗

PubMed1996

In utero repair of experimental myelomeningocele saves neurological function at birth.

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.

Animals↗

PubMed1996

Fetal endoscopic tracheal occlusion ('Fetendo-PLUG') for congenital diaphragmatic hernia.

Despite recent advances in surgical technique, posthysterotomy preterm labor remains a major determinant of postoperative fetal morbidity and mortality after in utero repair of congenital diaphragmatic hernia (CDH). Temporary fetal tracheal occlusion, or "PLUG" (Plug the Lung Until it Grows), reverses the pulmonary hypoplasia seen in experimental models of CDH and provides an alternative treatment strategy for some fetuses with CDH. Adaptation of current, minimally invasive surgical technology to the PLUG technique allows treatment of CDH without opening the uterus. In this report the authors describe a video-fetoscopic, intrauterine technique of tracheal occlusion (called Fetendo-PLUG) that could be used in human fetuses with CDH. The technique was developed in four fetal lambs that underwent video-fetoscopic intervention at 110 days' gestation (full term, 145 days), having undergone open creation of diaphragmatic hernias at 75 days. After maternal laparotomy and uterine exposure, the fetal head was located and a 5-mm curved, balloon-cuffed trocar was introduced through a uterine puncture directly into the fetal oral cavity. A steerable "bronchoscope" (with an instrument channel) was used to endoscopically intubate the trachea through the trocar, and the trocar was advanced over the bronchoscope and its balloon inflated to provide secure tracheal access below the vocal cords. Next, a 10-mm trocar was placed directly over the fetal neck, and the amniotic space was expanded with warm saline. A 5-mm laparoscope was introduced, and under simultaneous, dual video-fetoscopic (endotracheal and endoamniotic) visualization, a 1-mm nephrostomy puncture wire was advanced along the instrument channel of the bronchoscope, through the anterior wall of the trachea and fetal neck, into the amniotic space, then through the uterine wall to the outside. Withdrawal of the bronchoscope over the wire left a 5-mm endotracheal "trocar channel" along which a compressed, gelatin-encapsulated, polymeric foam insert (outer diameter, 4.8 mm) could be delivered by suture attachment to the guide wire. Once the foam was in its final endotracheal position, dissolution of the gelatin membrane allowed expansion of the foam to produce a water impervious tracheal occlusion. This two-trocar video-fetoscopic PLUG technique was performed successfully in all four fetuses, with a sequential decrease in operating time (median, 3.5 hours). Although two fetuses aborted postoperatively, the other two were carried successfully to term and demonstrated the anticipated physiological effects of adequate tracheal occlusion at the time of delivery.

Animals↗

PubMed1996

The fetal spinal cord does not regenerate after in utero transection in a large mammalian model.

OBJECTIVE: Regeneration and functional recovery after spinal cord transection do not occur in mammalian animals and humans postnatally. The goal of this study was to test whether in utero transection of the fetal spinal cord is succeeded by anatomic healing and functional recovery. METHODS: In five sheep fetuses, at 60 days of gestation and 75 days of gestation (term = 150 d), the spinal cord was completely transected at T10. The animals were delivered near term by cesarean section for clinical evaluation, measurement of cortical somatosensory evoked potentials, and morphological assessment. RESULTS: The newborn lambs demonstrated sensory-motor paraplegia, were incontinent of urine and stool, and exhibited a spinally generated, ambulatory pattern of the hindlimbs. No cortical somatosensory evoked potentials could be recorded in response to posterior tibial nerve stimulation, although potentials from the ulnar nerve, which enters the cord rostral to the lesion, were normal in all animals. Histologically, no neuronal connections across the transection site were identified. The cord proximal to the lesion was grossly normal, whereas distal to the transection, it appeared slightly smaller but with the cytoarchitecture preserved. CONCLUSIONS: Unlike in lower vertebrate and avian species, the fetal ovine spinal cord has no detectable spontaneous regenerative capabilities when transected during midgestation. Gap formation after transection, secondary posttraumatic cell death, and missing guiding channels for sprouting axons may be factors involved in the absence of any regenerative response.

Animals↗

PubMed1996

Fibrillin and elastin expression in skin regenerating from cultured keratinocyte autografts: morphogenesis of microfibrils begins at the dermo-epidermal junction and precedes elastic fiber formation.

The temporo-spatial expression of fibrillin and elastin in skin regenerating from autologous keratinocyte grafts was studied in three burned children. Skin biopsies taken between 5 days and 17 months after grafting were investigated by conventional immunofluorescence, confocal laser scanning, and electron microscopy. Fibrillin, the major component of 10-12nm microfibrils, appeared 5 days after grafting in a band-like fashion similar to collagen VII at the prospective basement membrane, and the formed the characteristic microfibrillar candelabra at the dermo-epidermal junction by fusion of several fine microfibrils to communicating microfibrils projecting downward into the reticular layer of the neodermis. Four to five months after grafting, several communicating microfibrils were connected to a web of horizontally undulating microfibrils of the neodermis which had developed independently. Elastin was first identified in the deeper neodermis 1 month after grafting as granular aggregates and 4 months after grafting on fibrillar structures and surrounding capillaries of the upper neodermis. Association of elastin with microfibrils in the papillary dermis was not detectable before month 17. Our findings suggest that the cutaneous microfibrillar apparatus develops simultaneously at both the dermo-epidermal junction and the reticular dermis and is a prerequisite for elastic fiber formation. In addition, it might be a driving force for the formation of the papilla-rete ridge pattern.

Adolescent↗

PubMed1996

Percutaneous access to the uterus for fetal surgery.

In utero repair of selected life-threatening malformations in the human fetus is now a clinical reality, yet fetal surgery continues to pose significant risks to both the mother and the unborn child. Preterm labor is a major problem directly related to the large uterine incision required for fetal exposure. Using technology developed for laparoscopic surgery, we have devised instruments and techniques to perform fetal endoscopic surgery. We now report a percutaneous technique for direct endoscopic access to the uterus. Minimally invasive fetoscopic surgery may expand the indications for fetal surgery by decreasing fetal risks, facilitating intervention earlier in gestation, and reducing preterm labor. This technique was developed in 4 fetal lambs who underwent endoscopic intervention at 105-110 days gestation (term = 145 days). Under ultrasound guidance, a 20-gauge spinal needle was advanced through the maternal abdomen, uterus, and directly into the amniotic cavity. Warmed saline was infused through the needle to expand the amniotic cavity. Next, a 5-mm balloon-tipped trocar was placed percutaneously with ultrasound guidance into the amniotic cavity. A 5-mm laparoscope was introduced and under endoamniotic vision two more 5-mm trocars were percutaneously placed. In all four sheep a 5-mm trocar was placed percutaneously into the gravid uterus. The most difficult step was puncturing through the amniotic membranes, but the sharp tip of the trocar facilitated getting into the amniotic cavity. Excellent visualization of the fetus was obtained with minimal uterine trauma. We have developed a fetoscopic technique in sheep for percutaneous placement of trocars into the uterus using ultrasound guidance. This approach allowed excellent visualization of the fetus with significantly less uterine trauma than open fetal surgery and is an essential prerequisite for future fetal endoscopic interventions.

Animals↗

PubMed1995

Human scalp hair follicle development from birth to adulthood: statistical study with special regard to putative stem cells in the bulge and proliferating cells in the matrix.

The depths of hair follicle compartments, and in particular of the bulge, the putative site of hair follicle stem cells, have not yet been determined in human scalp skin from infants, children or adolescents. This information is necessary in order to use the scalp safely as a donor site for skin grafts. We therefore investigated the development of the infundibulum, the bulge, Adamson's fringe, the B-fringe and the matrix by measuring the depths of these five follicular compartments in parietal scalp biopsy specimens from 100 patients ranging in age from 2 weeks to 21 years. The thickness of the epidermis and the dermis were also assessed. The correlations of these measurements with age were determined by regression analysis. The regression equation for the bulge was found to be b (microns) = 683.3 + 30.8y (r = 0.73; SEM = 145.5) where y is the age in years, and for the matrix it was m (microns) = 1616.2 + 90.4y (r = 0.76; SEM = 406.5); P < 0.0001 for the null hypothesis. The growth of the inferior portion below the bulge was not parallel but proportional to that of the superior portion. The relative position of the bulge in the dermis was stable, whereas the inferior portion moved progressively more deeply into the subcutis. These findings provide evidence for the postulated biologically advantageous localization of the bulge, and thus is a further argument in favour of the bulge as the site of follicular stem cells.

Adolescent↗

PubMed1995

Fetal endoscopic ('Fetendo') surgery: the relationship between insufflating pressure and the fetoplacental circulation.

Application of video-endoscopic surgery to the gravid uterus provides a new treatment option for the fetus with a correctable congenital anomaly. "Fetendo" surgery requires temporary enlargement of the uterine cavity to create a working space. Volume expansion of the amniotic space raises intrauterine pressure, which could increase placental vascular resistance and thereby reduce placental blood flow. To test this hypothesis, the authors developed a fetal sheep model to examine the relationship between insufflating pressure and flow in the placental circulation. Fetoplacental blood flow was measured via ultrasonic flow probes placed around the fetal common umbilical artery and the maternal uterine artery in five anesthetized 120-day-gestation ewes. Invasive feto-maternal monitoring permitted synchronous measurement of fetal mean arterial pressure, fetal central venous pressure, maternal mean arterial pressure, amniotic pressure, and fetal oxygen saturation, with calculated values for fetal and maternal placental vascular resistance. Amniotic pressure was raised from 10 mm Hg to 40 mm Hg in 5-mm Hg increments by a combination of saline amnioinfusion and external uterine compression. At amniotic pressures of 20 mm Hg or less, placental blood flow was preserved; however, elevation of amniotic pressure above 20 mm Hg resulted in a significant decrease in placental flow, with concomitant fetal hypoxia. The authors conclude that the relationship between intrauterine pressure, flow in the placental circulation, and fetal oxygen delivery must be considered when selecting intrauterine insufflation pressures for hysteroscopic intervention.

Amnion↗

PubMed1995

Scar formation in the fetal alimentary tract.

The aim of this study was to determine whether the fetal alimentary tract shares the unique scarless healing properties of fetal skin. Full-thickness incisional gastric wounds were created and sutured closed in fetal lambs at 60, 75, and 120 days' gestation (full term, 145 days), and in adult control sheep. At the time of harvest, 14 days postwounding, dense fibrous adhesions were found intraperitoneally in all fetal and adult animals. Histologically, all fetal and adult gastric wounds healed with pronounced scar formation. In contrast to the adult wound, there was no significant inflammatory response in the fetal wounds. Because scar formed in the absence of inflammation in fetal gastric wounds, there is no obvious relation between scarring and the inflammatory response at this location. This study shows that not all fetal tissues exhibit scarless repair properties.

Animals↗