Impact on postoperative, neonatal and 2-year neurodevelopmental outcomes of UA-AREDF during and after fetal spina bifida repair.

OBJECTIVE: Absent or reversed end-diastolic flow (AREDF) in the umbilical artery (UA) on Doppler is a known phenomenon during fetal interventions, such as fetal open spina bifida (OSB) repair. We aimed to evaluate the clinical importance of these Doppler findings by investigating the impact of UA-AREDF on postoperative, neonatal and 2-year neurodevelopmental outcomes. METHODS: This was a prospective study of pregnancies undergoing fetal OSB repair at the Zurich Center for Fetal Diagnosis and Therapy between 2010 and 2019. The group with UA-AREDF during or immediately after the intervention was compared to the group with normal UA Doppler. Primary endpoint was the FIGO scores of cardiotocography (CTG) 1, 2 and 6 h postoperatively and on day 1 after surgery. Secondary endpoints were the neonatal parameters and 2-year neurodevelopmental outcome assessed using the Bayley Scales of Infant and Toddler Development, Third Edition. RESULTS: Data of 130 patients were analyzed. None of the fetuses had UA-AREDF before OSB repair. Normal UA Doppler was observed in 107 (82%) patients and UA-AREDF was observed in 23 (18%) during or immediately after OSB surgery. UA-AREDF was more often observed after version of the fetus (P = 0.045). Seventeen (13%) cases had absent end-diastolic flow (UA-AEDF) and six (5%) cases had reversed end-diastolic flow (UA-REDF). UA-AREDF disappeared in all 23 cases within the first day after OSB surgery. One-third of all CTGs were restricted in oscillation after surgery, but no significant difference in CTG 1, 2 and 6 h postoperatively or on the first postoperative day was found between the UA-AREDF and normal-Doppler groups (P > 0.05). Gestational age at delivery, UA pH, 5-min Apgar score and birth weight were comparable between the two groups, and there was no difference in the 2-year neurodevelopmental outcome (P > 0.05). The neonatal and 2-year neurodevelopmental outcomes also did not differ significantly between the UA-REDF and UA-AEDF groups. CONCLUSIONS: Postoperative CTG abnormalities occur and recover at a similar rate in fetuses with transitory UA-AREDF and those with normal Doppler during fetal OSB repair. UA-AREDF during fetal OSB repair did not negatively influence postnatal or 2-year neurodevelopmental outcomes. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Association of uterine activity and maternal volatile anesthetic exposure during open fetal surgery for spina bifida: a retrospective analysis.

BACKGROUND: Recent warnings postulate a possible damaging effect of volatile anesthetics on the fetus. In our archive of fetal surgeries, we found wide variation in dosing of volatile anesthetics during spina bifida surgeries. We hypothesized that there was an association between volatile anesthetic exposure and uterine activity. METHODS: Sixty anesthesia records from spina bifida operations were assessed. We analyzed the course of the administered volatile anesthetic during surgery and calculated from each patient's anesthesia record the volatile anesthetic exposure expressed in vol%h. We divided the records into two post hoc groups of the 20 lowest exposure (Group L) versus the 20 highest exposure (Group H), and compared them for uterine activity and fetal heart rate. RESULTS: The number of contractions per hour was significantly greater in Group H (mean 1.3, SD ±â€¯1.2) compared with Group L (mean 0.5, SD ±â€¯0.6, P=0.049). There was no difference between the groups for the administration of the tocolytic drug atosiban (P=0.29). The course of the mean arterial pressure did not significantly differ but group H needed significantly more vasoactive medication (P <0.05). CONCLUSIONS: We found that a lower intra-operative volatile anesthetic exposure than recommended in the MOMS-trial (i.e. <2.0 minimum alveolar concentration [MAC]) was not associated with an increase in intra-operative uterine activity. This is an indication that during spina bifida surgery, 2.0 MAC may not be necessary to avoid potentially harmful uterine activity.

Systematic classification of maternal and fetal intervention-related complications following open fetal myelomeningocele repair - results from a large prospective cohort.

OBJECTIVE: To systematically categorise all maternal and fetal intervention-related complications after open fetal myelomeningocele (fMMC) repair of the first 124 cases operated at the Zurich Centre for Fetal Diagnosis and Therapy. DESIGN: A prospective cohort study. SETTING: Single centre. POPULATION: Mothers and fetuses after fMMC repair. METHODS: Between 2010 and 2019, we collected and entered all maternal complications following fMMC repair into the Clavien-Dindo classification. For fetal complications, a classification system based on the Medical Dictionary for Regulatory Activities terminology of Adverse Events was used including the preterm definitions of the World Health Organization. MAIN OUTCOME MEASURES: Systematic classification of maternal and fetal complications following fMMC repair. RESULTS: Gestational ages at surgery and birth were 25.0 ± 0.8 and 35.4 ± 2.0 weeks, respectively. In 17% of all cases, no maternal complications occurred. Maternal intervention-related complications were observed as follows: 69% grade 1, 36% grade 2, 25% grade 3, 6% grade 4 and 0% grade 5. In 34%, no fetal complications were noted; however, 43% of the fetuses developed a grade 1, 14% a grade 2, 8% a grade 3, 2% a grade 4 and 2% a grade 5 complication. CONCLUSION: This study raises awareness of complications following open fMMC repair; 6% of mothers and 2% of fetuses experienced a severe complication (grade 4) and perinatal death rate of 2% was observed (grade 5). These data are useful for prenatal counselling, they help to improve the system of fetal surgical care, and they allow benchmarking with other centres as well as comparison with fetoscopic approaches. TWEETABLE ABSTRACT: Systematic classification of all maternal and fetal intervention-related complications following open fMMC repair.

Intussusception in children: lessons learned from intestinal lymphoma as a rare lead-point.

BACKGROUND: Most cases of intussusception in children are idiopathic. Rarely, a malignant disease such as intestinal lymphoma may cause intussusception. Due to dramatic changes of expected outcome with chemotherapy regime alone, the surgical management of patients with intestinal lymphoma presenting with intussusception has to be reevaluated. METHODS: Retrospective chart review from May 2011 to February 2017. We included all patients with intestinal lymphoma presenting with intussusception. RESULTS: We found five patients with a mean age of 6.4 years (range 3-16). The most common presenting symptom was abdominal pain for several weeks which had acutely worsened. In all but one patient an ultrasound before pneumatic or hydrostatic reduction showed a finding suspicious of a pathological lead-point. Pneumatic or hydrostatic reduction was attempted in all patients, no complications were noted. In one patient reduction was not successful. Recurrence after reduction occurred in two patients. Two patients needed surgery, three had a percutaneous ultrasound-guided biopsy for diagnostic purposes. All patients had aggressive mature B cell non-Hodgkin lymphoma. CONCLUSION: A high index of suspicion for the presence of a pathological lead-point in children older than 4 years and children with recurrent intussusception is necessary in patients presenting with intussusception. Malignant, highly aggressive B cell non-Hodgkin lymphoma, although rare, must actively be searched for. Pneumatic or hydrostatic reduction should remain the first line treatment in most cases.

Intestinal IMINO transporter SIT1 is not expressed in human newborns.

The expression of amino acid transporters in small intestine epithelia of human newborns has not been studied yet. It is further not known whether the maturation of imino acid (proline) transport is delayed as in the kidney proximal tubule. The possibility to obtain small intestinal tissue from patients undergoing surgery for jejunal or ileal atresia during their first days after birth was used to address these questions. As control, adult terminal ileum tissue was sampled during routine endoscopies. Gene expression of luminal imino and amino acid transporter SIT1 (SLC6A20) was approximately threefold lower in newborns versus adults. mRNA levels of all other luminal and basolateral amino acid transporters and accessory proteins tested were similar in newborn mucosa compared with adults. At the protein level, the major luminal neutral amino acid transporter B0AT1 (SLC6A19) and its accessory protein angiotensin-converting enzyme 2 were shown by immunofluorescence to be expressed similarly in newborns and in adults. SIT1 protein was not detectable in the small intestine of human newborns, in contrast to adults. The morphology of newborn intestinal mucosa proximal and distal to the obstruction was generally normal, but a decreased proliferation rate was visualized distally of the atresia by lower levels of the mitosis marker Ki-67. The mRNA level of the 13 tested amino acid transporters and accessory proteins was nonetheless similar, suggesting that the intestinal obstruction and interruption of amniotic fluid passage through the small intestinal lumen did not affect amino acid transporter expression. NEW & NOTEWORTHY System IMINO transporter SIT1 is not expressed in the small intestine of human newborns. This new finding resembles the situation in the proximal kidney tubule leading to iminoglycinuria. Lack of amniotic fluid passage in small intestinal atresia does not affect amino acid transporter expression distal to intestinal occlusion.

Myelinated and unmyelinated nerve fibers reinnervate tissue-engineered dermo-epidermal human skin analogs in an in vivo model.

PURPOSE: The clinical application of autologous tissue-engineered skin analogs is an important strategy to cover large skin defects. Investigating biological dynamics, such as reinnervation after transplantation, is essential to improve the quality of such skin analogs. Previously, we have examined that our skin substitutes are reinnervated by host peripheral nerve fibers as early as 8 weeks after transplantation. Here, we wanted to investigate the presence and possible differences regarding myelinated and unmyelinated host nerve fibers 15 weeks after the transplantation of light and dark human tissue-engineered skin analogs. METHODS: Human epidermal keratinocytes, melanocytes, and dermal fibroblasts were isolated from human light and dark skin biopsies. Keratinocytes and melanocytes were seeded on fibroblast-containing collagen type I hydrogels after expansion in culture. After additional culturing, the tissue-engineered dermo-epidermal skin analogs were transplanted onto full-thickness skin wounds created on the back of immuno-incompetent rats. Skin substitutes were excised and analyzed 15 weeks after transplantation. Histological sections were examined with regard to the ingrowth pattern of myelinated and unmyelinated nerve fibers into the skin analogs using markers, such as Substance P, NF200, and S100-Beta. RESULTS: We found myelinated and unmyelinated peripheral host nerve fibers 15 weeks after transplantation in the dermal part of our human skin substitutes. In particular, we identified large-diameter-myelinated Aß- and Aδ-fibers, and small-diameter C-fibers. Furthermore, we observed myelinated nerves in close proximity to CD31-positive blood capillaries. In the long run, both types of ingrown host fibers showed an identical pattern in both light and dark skin analogs. CONCLUSION: Our data suggest that myelinated and unmyelinated peripheral nerves reinnervate human skin substitutes in a long-term in vivo transplantation assay. Our tissue-engineered skin analogs attract A- and C-fibers to supply both light and dark skin analogs. Potentially, this process restores skin sensitivity and has, therefore, a significant relevance with regard to future application of autologous pigmented dermo-epidermal skin substitutes onto patients.

Successful grafting of tissue-engineered fetal skin.

PURPOSE: Fetal repair of spina bifida results in improved outcomes and has therefore become a standard clinical procedure in some highly specialized centers. However, optimization of the procedure technique and timing is needed. Both might be achieved by facilitating the procedure using laboratory-grown fetal skin substitutes. The aim of this study was therefore to test in vivo the suitability of such a fetal skin substitute for an in utero application. METHODS: Collagen-based hydrogels containing fetal ovine fibroblasts were seeded with fetal ovine keratinocytes and transplanted on immuno-incompetent nu/nu rats. After 3 weeks, grafts were harvested and analyzed histologically and by immunohistochemistry. RESULTS: Laboratory-grown fetal ovine dermo-epidermal skin substitutes showed successful engraftment at 3 weeks. Histologically, grafts revealed a neo-dermis populated by fibroblasts and with ingrowth of vessels, and an epidermis with an adult-like, mature appearance depicting clearly basal, spinous, granular, and a corneal layer. Immunostaining confirmed a physiologically organized epidermis. CONCLUSION: Fetal dermo-epidermal skin substitutes of ovine origin can successfully be grafted in vivo. In a next step, we will have to test whether favorable results can also be obtained when grafts are used in utero. If so, then human fetal spina bifida repair using laboratory-grown autologous fetal skin for defect closure may be envisaged.

Experimental tissue engineering of fetal skin.

PURPOSE: In some human fetuses undergoing prenatal spina bifida repair, the skin defect is too large for primary closure. The aim of this study was to engineer an autologous fetal skin analogue suitable for in utero skin reconstruction during spina bifida repair. METHODS: Keratinocytes (KC) and fibroblasts (FB) isolated from skin biopsies of 90-day-old sheep fetuses were cultured. Thereafter, plastically compressed collagen hydrogels and fibrin gels containing FB were prepared. KC were seeded onto these dermal constructs and allowed to proliferate using different culture media. Constructs were analyzed histologically and by immunohistochemistry and compared to normal ovine fetal skin. RESULTS: Development of a stratified epidermis covering the entire surface of the collagen gel was observed. The number of KC layers and degree of organization was dependent on the cell culture media used. The collagen hydrogels exhibited a strong tendency to shrink after eight to ten days of culture in vitro. On fibrin gels, we did not observe the formation of a physiologically organized epidermis. CONCLUSION: Collagen-gel-based ovine fetal cell-derived skin analogues with near normal anatomy can be engineered in vitro and may be suitable for autologous fetal transplantation.

Assessment of long-term donor-site morbidity after harvesting the latissimus dorsi flap for neonatal myelomeningocele repair.

BACKGROUND AND AIM: The latissimus dorsi flap (LDF) has been employed very successfully over decades to cover large soft-tissue defects. Its donor-site morbidity has been extensively investigated in adults - but not in children - and is considered to be nonrestrictive. The aim of this long-term study was to assess donor-site morbidity with the modified Constant score more than 8 years after coverage of large myelomeningocele (MMC) defects with a reverse latissimus dorsi flap. METHODS: Within the first days after birth, the reverse latissimus dorsi muscle flap was used uni- or bilaterally in three neonates to cover a large MMC defect. Bilateral shoulder function was tested more than 8 years postoperatively according to the modified Constant score. RESULTS: The mean age at follow-up was 11.7 years. None of the patients experienced any pain or shoulder restrictions during normal daily activities. They all managed to position both of their arms comfortably above the head. Forward flexion was normal in all patients as was abduction and external rotation. Dorsal extension was minimally reduced on the operated side. Internal rotation was symmetric in all patients; the extent of active movement varied from excellent to poor. CONCLUSIONS: Our long-term data suggest that there is no specific and significant impairment of shoulder function after using the distally pedicled reverse LDF for neonatal MMC repair.

Osmotic expanders in children: no filling--no control--no problem?

BACKGROUND: Self-filling, hydrogel-based osmotic tissue expanders have been successfully used for several years, mainly in adult patients. We wanted to test this novel device in pediatric plastic and reconstructive surgery. MATERIAL AND METHODS: Between November 2004 and September 2009, we implanted 53 osmotic tissue expanders following standard surgical principles in a total of 30 children and adolescents with burn scars, congenital nevi, alopecia, or foot deformities. RESULTS: All expanders reached their predicted volume within 6 weeks and 51 (96.2%) produced a sufficient amount of additional skin for the intended coverage of the defect. A serious infection precluding the planned reconstructive procedure occurred with 2 expanders (3.8%). Minor complications occurred at 6 implantation sites (11.4%), and consisted of small necrotic areas and perforations (n = 3) and minor infections (n = 3). These problems could be controlled and did not interfere with the subsequent plasty. The final results recorded at the last follow-up (mean: 21 months, range: 9-48 months) were rated as excellent in 25, good in 19, moderate in 6, and poor in 1 patient. CONCLUSION: This is apparently the largest pediatric series in which self-filling expanders have been used. The data obtained indicates that self-filling expanders can be safely and effectively used for various plastic, reconstructive and orthopedic procedures in children and adolescents. The fact that numerous painful and distressing filling sessions are obviated with these expanders is particularly beneficial for those children too young to understand and cooperate. Moreover, this approach minimizes the risk of infection and lowers costs.

Novel treatment for massive lower extremity avulsion injuries in children: slow, but effective with good cosmesis.

BACKGROUND: Extended avulsion injuries are associated with significant loss of skin and subcutaneous fat, leaving the reconstructive surgeon with the challenge of substituting all tissues lost in the best possible way. We wanted to test whether the combined use of a Vacuum Assisted Closure system (VAC) and Integra Dermal Regeneration Template (IDRT) matched the required treatment profile encompassing initial control of infection, remodeling of body contours, and reconstruction of near normal skin. MATERIALS AND METHODS: 4 children with massive lower extremity avulsion injuries were treated with early necrosectomy, VAC application for 3-5 weeks for wound cleansing and wound bed conditioning, subsequent implantation of IDRT, and finally autologous split thickness skin grafting (STSG) for definitive wound closure. Thereafter, a standard rehabilitation program was used. The key parameters of VAC and IDRT application, take rates of IDRT and STSG, complications, length of stay, and final outcome were recorded. RESULTS: In all patients, early removal of necrosis and infection control was successfully achieved. Continuous VAC application fostered the formation of a several millimeters thick new tissue layer partly compensating for the lost hypodermis. IDRT implantation and subsequent STSG yielded take rates of nearly 100% and both functionally and cosmetically excellent long-term results. There were no major complications. CONCLUSION: The combination of VAC and IDRT in children with massive leg avulsion injuries is feasible, safe, and delivers high-quality long-term outcomes that appear to justify the multiple operative procedures, the long hospitalization times, and the comparatively high costs entailed.

Management of prenatally diagnosed abdominal lymphatic malformations.

INTRODUCTION: Abdominal lymphatic malformations (ALM) are rare congenital malformations that can regress spontaneously or lead to serious complications. Thus, the appropriate management may be challenging, particularly since pertinent literature is missing. We present our experience in the management of 5 patients with prenatally diagnosed ALM and their outcome and propose a decision-making algorithm. MATERIAL AND METHODS: We retrospectively reviewed the history, diagnostics, therapy, complications, and outcome of 5 patients with a prenatal diagnosis of ALM, referred to our department between January 2006 and February 2008. RESULTS: ALM was prenatally diagnosed by ultrasound in all patients (gestational age 21, 23, 23, 32, and 34 weeks). MRI was performed pre- and postnatally in one patient and postnatally in another. Clinical symptoms ranged from none to respiratory distress and abdominal compartment syndrome. One ALM involuted. 2 patients underwent primary OK-432 treatment. This led to a 70% size reduction in one patient. The other developed massive intracystic bleeding and required emergency surgery. 2/3 patients with surgery needed segmental bowel resection and 3/3 stayed recurrence-free. Complications included one partial inferior vena cava thrombosis after surgery, one subileus, and one hemorrhage after OK-432 application. CONCLUSION: Asymptomatic and regressing ALM are best managed conservatively ("watchful waiting") while symptomatic ALMs require surgery. Further studies are necessary to determine the ideal timepoint for intervention for non-regressing ALM.

Giant naevus, giant excision, eleg(i)ant closure? Reconstructive surgery with Integra Artificial Skin to treat giant congenital melanocytic naevi in children.

BACKGROUND: The optimal surgical treatment of giant congenital melanocytic naevi remains a considerable challenge in reconstructive surgery. None of the currently available techniques is universally applicable. The goal of this pilot study was to test Integra Artificial Skin (Integra) in the surgical treatment of giant congenital melanocytic naevi. METHODS: Between May 2000 and March 2004, Integra was used in 12 children (n=12; aged seven months to 11 years, mean 3.8 years). Giant congenital melanocytic naevi covered 1-12% of the total body surface area (mean 4.2%) located over the trunk in 50%, and over face and extremities in 25% each. RESULTS: In eight children, Integra implantation was primarily successful; in four patients a partial or complete removal and re-implantation was necessary due to complications. The final take rate of Integra ranged from 95-100%, except for one patient with a take rate of 30% (mean 93%). Second stage split-thickness skin grafting yielded take rates from 95-100% (mean 98%). Functional and cosmetic outcome was rated excellent in 58%, good in 25% and fair in 17% (follow-up six months to four years, mean 2.2 years). CONCLUSIONS: These results suggest that Integra is a new and valid method to successfully treat giant congenital melanocytic naevi in early childhood in a definitive manner and with high-quality results.

Impact of carbon dioxide versus air pneumoperitoneum on peritoneal cell migration and cell fate.

BACKGROUND: Postoperative systemic immune function is suppressed after open abdominal surgery, as compared with that after minimally invasive abdominal surgery. As a first line of defense, peritoneal macrophages (PMo) and polymorphonuclear neutrophil granulocytes (PMNs) are of primary importance in protecting the body from microorganisms. Previous studies have shown changes in these cell populations over time after open versus laparoscopic surgery. This study aimed to investigate the dynamics of cell recruitment and clearance of peritoneal cells. METHODS: Female NMRI mice (33 +/- 2 g) were randomly assigned to carbon dioxide (CO2) or air insufflation. Intravasal cells with phagocytic capabilities were selectively stained by intravenous injection of the fluorescent dye PKH26 24 h before surgery. Gas was insufflated into the peritoneal cavity through a catheter, and the pneumoperitoneum was maintained for 30 min. Peritoneal lavage was performed 1, 3, 8, or 24 h after surgery. Apoptotic cells were assessed by flow cytometry using a general caspase substrate. RESULTS: The total peritoneal cell count did not differ between groups. The PKH26-positive PMo level was significantly increased after CO2, as compared with air, at 1 h and 24 h. The ratio of apoptotic PMo did not differ between the groups. In the peritoneal lavage, polymorphonuclear leukocytes (PMNs) were tripled in the air group, as compared with the CO2 group, whereas the ratio of apoptotic PMNs was significantly decreased. There was a higher fraction of PKH26-positive PMNs after air exposure, as compared with that after CO2. CONCLUSIONS: Air exposure triggered a higher transmigration rate of PMNs from the blood compartment into the peritoneal cavity and decreased PMN apoptosis, as compared with CO2. The lower proportion of PKH26-positive peritoneal macrophages in the air group might have been attributable to a higher inflammatory stimulation than in the CO2 group, leading to increased emigration of PMo to draining lymph nodes. All the findings underscore a complex cell-specific regulation of cell recruitment and clearance in the peritoneal compartment.

Medial clavicular epiphysiolysis in children: the so-called sterno-clavicular dislocation.

We retrospectively reviewed six pediatric cases of medial clavicular injury, i.e., epiphyseal separation (Salter/Harris type I or II injury), diagnosed between 1993 and 1997. The clavicular metaphysis was displaced posteriorly in three cases and anteriorly in three. On conventional radiographic views the diagnosis was initially missed in two of three retrosternal dislocations. A special X-ray projection (described by Heinig) or computed tomography (CT) permitted correct diagnosis. Anterior dislocations were immediately and correctly diagnosed. Closed reduction successfully treated retrosternal displacement in two of the three patients. The third patient needed open reduction and internal fixation. Open reduction and internal fixation had to be performed in all three patients with anterior displacement. Follow-up assessment showed perfect functional results in all cases. Direct visualization during open reduction, which was necessary in four of six cases, yielded clear evidence that the so-called sternoclavicular dislocation in children and young adults is, in fact, a fracture of the medial growth plate with posterior or anterior displacement of the metaphysis.

Oxygen-regulated expression of TGF-beta 3, a growth factor involved in trophoblast differentiation.

The transforming growth factor-beta 3 (TGF-beta 3) is involved in oxygen-dependent differentiation processes during placental development and pregnancy disorders. However, the importance of oxygen partial pressure for the regulation of TGF-beta 3 expression is presently unclear. We and others presented preliminary evidence that the hypoxia-inducible factor-1 (HIF-1) confers TGF-beta 3 transcription but it was unknown whether this occurred directly or indirectly. To analyze how HIF-1 regulates TGF-beta 3 gene transcription, we cloned and sequenced the mouse TGF-beta 3 promoter region. Multiple putative HIF-1 binding sites (HBSs) were identified, many of which co-localized with two G+C rich CpG islands 5' to the TGF-beta 3 transcription start site. A 6.8 kb fragment of the TGF-beta 3 promoter induced reporter gene expression under hypoxic conditions or when treated with an iron chelator known to stabilize and activate the HIF-1 alpha subunit. Deletion of a 2.4 kb fragment upstream of the distal CpG island abolished inducibility of reporter gene expression. Two HBSs (HBS1 and HBS6) that bound the HIF-1 protein could be identified within this 2.4 kb fragment. These results suggest that TGF-beta 3 gene expression is directly regulated by HIF-1.

Does cartoon movie distraction decrease burned children's pain behavior?

The purpose of this study was to evaluate cartoon movie viewing as a practical and low-cost intervention to decrease burned children's pain behavior during dressing changes. Thirteen children, 4 to 12 years of age, with a mean TBSA burn of 7.9% were assessed using a reversal, single-subject experimental design. The experimental condition consisted of the presentation of a cartoon movie as a nonpharmacologic intervention in conjunction with a standardized analgesic medication. In the control condition children's pain was treated with the standardized analgesic medication only. Behavioral distress was measured during the first six dressing changes postburn with the Observational Scale of Behavioral Distress. No significant effect of cartoon movie distraction on observed behavioral distress in patients was found. Interrater reliability of the Observational Scale of Behavioral Distress was good (kappa =.87-.98). Wound debridement was found to be the most painful part of the dressing change. A simple, easily applicable, and low-cost distraction intervention such as presenting cartoon movies does not seem to be sufficiently powerful to measurably reduce burned children's distress during dressing changes. Findings are based on purely observational data. Inclusion of self-report measures in future studies might reveal intervention effects on anxiety and subjective pain perception.

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.

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.