Functional MR imaging assessment of a non-responsive brain injured patient.

Functional magnetic resonance imaging (fMRI) was requested to assist in the evaluation of a comatose 38-year-old woman who had sustained multiple cerebral contusions from a motor vehicle accident. Previous electrophysiologic studies suggested absence of thalamocortical processing in response to median nerve stimulation. Whole-brain fMRI was performed utilizing visual, somatosensory, and auditory stimulation paradigms. Results demonstrated intact task-correlated sensory and cognitive blood oxygen level dependent (BOLD) hemodynamic response to stimuli. Electrodiagnostic studies were repeated and evoked potentials indicated supratentorial recovery in the cerebrum. At 3-months post trauma the patient had recovered many cognitive & sensorimotor functions, accurately reflecting the prognostic fMRI evaluation. These results indicate that fMRI examinations may provide a useful evaluation for brain function in non-responsive brain trauma patients.

Successful repair of esophageal injury using an elastin based biomaterial patch.

An esophageal injury with significant tissue loss is very difficult to repair. We conducted an in vivo study to test our elastin based acellular biomaterial patch to repair such defect. The patch was made from porcine aorta, by decellularization and sterilization. Collagen fibers were preserved to retain mechanical strength and enhance cellular in-growth. Ten domestic pigs underwent right thoracotomy. A 2 cm circular defect was made on the distal esophagus, excising half its circumference, and was repaired using the biomaterial patch and sutures. Soon after the procedure, the animals resumed oral feeding. They were followed for clinical status, weight gain, barium studies, and endoscopic studies, and were killed after 6 weeks to 4 months. All ten animals survived long term, with a procedure success rate of 100% (10 of 10). With the exception of one pneumothorax, no complications occurred, and all animals resumed oral feeding and gained weight. Endoscopic studies showed mucosal coverage by 6 weeks, with minimal stricture at the repair site. Excised specimens showed complete mucosal coverage with regeneration of all three layers. Our biomaterial patch can be used safely and reliably for repair of esophageal injury with significant tissue loss when repaired immediately as in our experiment.

Interleukin-6 promotes post-traumatic healing in the central nervous system.

The central nervous system (CNS) is an immune-privileged site where the role of immune cells and mediators in traumatic brain injury is poorly understood. Previously we have demonstrated that interleukin (IL)-6, a cytokine that acts on a wide range of tissues influencing cell growth and differentiation, is an agonist for vascular endothelial growth factor (VEGF), in in vitro vascularization assays for brain microvessel endothelial cells. In this present work we focus on the role of IL-6 in promoting tissue repair in the CNS in vivo. An aseptic cerebral injury (ACI) was created in the right parietal cortex, using both wild type (C57Bl/6J) and IL-6-deficient (C57Bl/6J-IL-6-/-) mice to study the consequences of the absence of IL-6 on the pathology of brain injuries. We monitored the immediate, early, and late responses to this traumatic injury by characterizing several histologic features in the CNS at days 1, 4, 7 and 14 following injury. Acellular necrosis, cellular infiltration, and re-vascularization were characterized in the injured tissues, and each of these histologic features was individually graded and totaled to assign a healing index. IL-6-deficient mice were found to have a comparatively slower rate of recovery and healing. Furthermore, fluorescein isothiocyanate (FITC)-dextran intravenous injection demonstrated leaky vessels in IL-6-deficient but not in wild type animals following ACI. Additionally, chronic expression of IL-6 in the CNS using transgenic GFAP-IL-6 mice resulted in more rapid healing following ACI. The accelerated tissue repair in GFAP-IL-6 transgenic animals is primarily due to extensive re-vascularization as detected by endothelial cell markers. Combined, this data suggests an important role of IL-6 in tissue repair processes following traumatic injury in the CNS.

Use of a new elastin patch and glue for repair of a major duodenal injury.

Major duodenal injury with significant tissue loss causes high morbidity and mortality. Our new elastin based heterograft combined with small intestinal submucosa (SIS) and biodegradable glue could be used for repair of such defects. Twenty-four domestic pigs were anesthetized and underwent celiotomy. A 2 cm circular defect was created at the second portion of the duodenum with scissors, excising one-half of its circumference. Our elastin patch, combined with SIS, was applied to cover the defect using biodegradable cyanoacrylate glue and a few sutures. It was then covered with omentum. Animals were followed by weight gain, endoscopic evaluation, and upper GI barium studies. After 2-5 months, animals were sacrificed to obtain specimens. One failed in 3 days due to a technical problem, and one failed in 20 days due to an abdominal abscess. The other 22 animals (22/24, 91.7%) did well, gaining weight. Early endoscopic studies (5-14 d) showed an intact patch. Upper GI studies showed varying degrees of stenosis at the repair site at 3-4 months. Sacrifice after 2-5 months showed complete healing of the defect and a dissolved patch. Our new elastin patch material provides a reliable barrier for repair of duodenal injury, and the biodegradable glue provides quick and easy watertight tissue fusion for our patch.

Effects of E. coli endotoxin on rat plasma angiotensin converting enzyme activity in vitro and in vivo.

Angiotensin converting enzyme (ACE), a glycoprotein, is found in high concentration in pulmonary capillary endothelial cells. Several investigators have studied the relationship between various direct and indirect pulmonary insults and ACE activity and in some cases have found conflict. In an attempt to clarify this relationship we have examined the effect of endotoxin on rat plasma ACE activity in vitro and in vivo. We used the synthetic ACE substrate 3H-BPAP and the assay described by Catravas and Gillis [J Pharmacol Exp Ther 217:263-270, 1981]. In vitro, a statistically significant concentration-dependent reduction in ACE activity was demonstrated (p less than .005). In vivo an intravenous dose of endotoxin (20 mg/kg) alone resulted in no significant change in plasma ACE activity. However, the combination of intravenous endotoxin (20mg/kg) and mild hemorrhage (5-10% of blood volume) caused a statistically significant reduction in plasma ACE activity by 15 min as compared to control rats with hemorrhage only (39% vs. 66%, p less than .005). This reduction persisted at 30 and 60 min. However, by 180 min ACE activity was no longer statistically different from control values. We have demonstrated an acute reduction of plasma ACE activity in the endotoxemic rat that appears to be dependent on the amount of circulating endotoxin and the presence of mild blood loss.

Long-term follow-up of patients with gastroschisis.

Long-term follow-up of children with gastroschisis has been made possible by the increased survival of these infants over the past 20 years. We have observed that children with isolated gastroschisis defects exhibit normal growth and development beyond 5 years of age without significant bowel sequelae. Infants with gastroschisis with concomitant bowel atresia or complications who require small bowel resection are at a greatly increased risk for long-term bowel problems and abdominal complaints.

Selective management of gastroschisis.

Mortality of patients with gastroschisis has decreased from nearly 90% to 13% (14 of 106) during the period from 1967 to 1984. Coincident with advances in perioperative management, including parenteral nutrition and mechanical ventilation, has been the introduction of staged reduction of the viscera using prosthetic material. To assess the relative merits of primary closure, skin flap coverage, and silo reduction, operative treatment of 106 consecutive infants with gastroschisis was reviewed. Primary fascial closure was accomplished in 54 patients (52%). When fascial approximation resulted in excessive intra-abdominal pressure, the viscera were covered with lateral skin flaps in 10 infants (10%), or the defect was closed after staged reduction with a prosthetic silo in 40 infants (38%). Detailed analysis of the hospital records revealed no significant differences between the primary closure, skin flap, and silo groups with regard to duration of ileus (22 +/- 25, 30 +/- 27, 31 +/- 30 days), length of hospitalization (39 +/- 36, 54 +/- 37, 53 +/- 39 days), or mortality (6, 20, 18%). Respiratory, septic, hemorrhagic, renal, and wound complications occurred in significantly fewer patients with primary closure (36%) and skin flap coverage (30%) than in those with silos (68%) (p less than 0.05). Postoperative mortality was 12% (12/104) and was most often due to respiratory insufficiency (35%) or nonviable small bowel (19%). Primary fascial closure may be accomplished safely in a majority of patients with gastroschisis. However, no single operative strategy is ideal for all patients with gastroschisis, and initial treatment of individual defects should be tailored to the degree of visceroabdominal disproportion.

Ventral hernia in the treatment of omphalocele and gastroschisis.

Twenty-three patients with gastroschisis or omphalocele undergoing delayed ventral herniorrhaphy were reviewed. The ventral defects resulted from elective skin flap coverage in 15 patients, prosthetic silo failure in five, and nonoperative management using escharotic agents in three. Herniorrhaphy was performed at 2 months to 15 years of age. Fascial closure was achieved in a single procedure in 15 patients (65%) and with multiple operations involving prosthetic material in five patients (22%). Three patients (13%) had prosthetic material left in their defects without sequelae. There was no operative mortality from interval herniorrhaphy, and complications were minor. We conclude that conversion of a gastroschisis or an omphalocele to a ventral hernia is strategically useful in an infant with a giant defect, prosthetic silo failure, or when associated anomalies preclude early definitive surgery.