Best practices for the prevention and treatment of pressure ulcers.

In this article, the Canadian Association of Wound Care puts forward 12 recommendations for best practices in the prevention and treatment of pressure ulcers that focus on an interdisciplinary patient-centered approach. These recommendations are a synthesis of the Agency for Health Care Policy and Research guidelines, European guidelines, and current literature as interpreted by the Canadian experience and achieved through a national consensus panel. The article concludes that best practice guidelines must be fluid documents that respond to new evidence and experience.

The role of Apligraf in the treatment of venous leg ulcers.

A cultured, allogeneic, bi-layered human skin equivalent has recently become available to help clinicians manage difficult-to-heal venous ulcers. This skin equivalent has an epidermis and dermis similar to human skin. Its living keratinocytes and fibroblasts are from cultured cell banks derived from human neonatal foreskin. Because the skin equivalent is made up of viable human cells, it cannot be terminally sterilized. Safety concerns, which have been addressed, include the risk of possible transmission of infection, immunogenicity, immunological graft rejection, and tumor formation. However, the maternal blood of the neonatal donor and the master cell banks are screened for infectious agents. Additionally, the human skin equivalent is produced under strict aseptic control, with sterility continuously monitored by the Good Manufacturing Processes. This paper reviews the characteristics of this human skin equivalent and provides practice guidelines.

Orbital volumetric analysis: clinical application in orbitozygomatic complex injuries.

Fifteen patients with unilateral orbitozygomatic complex fractures and five with bilateral injuries were analyzed with respect to the differences in orbital volume between the affected and the uninjured, or other, side. The study was conducted using the ALLEGRO Workstation and software package from ISG Technologies, which was capable of calculating volume partitions from either axial or coronal images. Patients without postoperative enophthalmos demonstrated a maximum volume difference of 3.8%; those with enophthalmos demonstrated differences of 4% or greater. The Critical Volume Difference at which enophthalmos becomes clinically apparent (whereby the orbital-corneal distance measured by Hertel exophthalmometry is greater than 3 mm on the affected side) is in the range of 4% to 5%. Volume analysis of the orbits by manipulation of the computed tomography data may allow a better understanding of changes in orbital configuration, which can result in better-directed primary and secondary reconstructions.

Topical putrescine (Fibrostat) in treatment of hypertrophic scars: phase II study.

Previous studies indicated that tissue transglutaminase plays a role in the cross-linking of type III procollagen in wound matrices and that this may be inhibited by 50 mM putrescine in vitro. For this reason, the clinical effect of 50 mM putrescine in a eutectic vehicle (Fibrostat) was studied in this phase II double-blind crossover study in 43 patients. Twenty of the patients had had recent surgery and were studied for product safety rather than efficacy. No toxic effects were observed in this group of patients, and only 1 of the 23 unoperated patients had a rash during treatment. The observed effect of Fibrostat versus sham treatment of 1 month's duration in active hypertrophic scar was a significant improvement of hypertrophy in 23 patients during the Fibrostat treatment arm, regardless of the order in which treatment was received. It is suggested that Fibrostat is a safe therapeutic agent for treatment of hypertrophic scar. Clinical examples to illustrate its use are given.

Inhibition of tissue transglutaminase and epsilon (gamma-glutamyl) lysine cross-linking in human hypertrophic scar.

Immunohistochemical staining with monoclonal antibody to tissue transglutaminase was used to study cryostat sections of human skin wounds. The enzyme was found in acute wounds and chronic hypertrophic scars but not in normal mature scars. Because tissue transglutaminase is responsible for the formation of isopeptide cross-links, a two-stage high-performance liquid chromatographic analysis was used to quantitate the epsilon (gamma-glutamyl) lysine cross-link produced by various types of wound tissues. Eighteen patients with hypertrophic scars between 6 months' and 10 years' duration after injury underwent a double-blind trial with putrescine 50 mmol/L in a eutectic vehicle for 2 months under nonocclusive dressings (Biofill). For the control portion of the same or different scar, sham vehicle and non-occlusive dressing were simultaneously applied. Both scars were harvested at biopsy or elective revision surgery 2 months later. After homogenization and exhaustive proteolysis, digests were studied with the use of high-performance liquid chromatography analysis. The results of treatment were a significant decrease in the levels of isopeptide cross-link formation from 0.018 +/- .006 nmol/micromol amino acids in untreated scars to 0.008 +/- .001 nmol/micromol amino acid in the treated group (p < 0.05). The isopeptide cross-link content in treated scars was nearly as low as that in normal mature scars (0.003 +/- 0.001 nmol/micromol amino acid). These results show that cross-link formation by tissue transglutaminase activity is inhibited during treatment of hypertrophic scar by putrescine. These results support the possible therapeutic use of topical putrescine in the treatment of hypertrophic scar formation.

Importance of crossover innervation in digital nerve repair demonstrated by nerve isolation technique.

This study was conducted to determine how testing of nerve repair using nerve isolation techniques compares with standard testing. Nerve isolation consisted of double-gloving, leaving the study finger free, and administering local anesthetic blocks to all other sensory contributions in the exposed digit. Ten patients with 13 single digital nerve repairs of equally severe injuries were studied at a mean of 41 months postoperatively. Standardized tests yielded an excellent result in 77% for static two-point discrimination (S2pd), 85% for moving two-point discrimination (M2pd), and 46.2% for Semmes-Weinstein monofilaments (SWMF). The same studies combined with nerve isolation yielded an excellent result in only 43% for S2pd, 43% for M2pd, and 0% for SWMF. These results indicate a statistically significant difference and the importance of crossover innervation from intact nerves in the long-term result of digital nerve repair. Nerve isolation study techniques are an important adjunct in assessing the outcome of nerve repair and are the only method of evaluating the true end result of nerve regeneration following neurorrhaphy.

Digital nerve repair: relationship between severity of injury and sensibility recovery.

The purpose of this study was to measure the relationship between severity of injury and sensibility outcome. This was done by a retrospective study of 37 digital nerve repairs in 26 patients, with a mean follow-up of 35 months. All patients underwent complete hand examination and standard nerve testing, including static and moving two-point discrimination, Semmes-Weinstein monofilaments (SWMF), object recognition, and the pick-up test. A hand injury severity scoring system based on wound characteristics, mechanism of injury, and number of structures involved was then developed. Severity grading led to three classes, and each study group was well matched. Subjectively, all patients considered their outcome as either good or excellent. Objective results are reviewed individually for each test, with the overall combined result of static and moving two-point discrimination being excellent (Highet S4) in 81% for class I, 41% for class II, and 31% for class III, all different at a statistically significant level. We concluded that the severity of injury in the hand can be graded and does have a relationship to the functional end result of digital nerve repair.

Effect of putrescine on tissue transglutaminase activity in wounds: decreased breaking strength and increased matrix fucoprotein solubility.

Topical application of putrescine, a transglutaminase inhibitor, for 3 days directly to rat skin wounds produced a significant average decrease of 48 percent in wound breaking strength in test animals from 8 pairs studied between day 5 and day 10 after wounding. No external or systemic toxic effects of putrescine were seen with localized topical application of 50 mM putrescine for 3 days in any of the test rats (n = 12), and no systemic toxicity was seen in rabbits (n = 4) after topical exposure to 50 mM putrescine for 3 weeks. Quantitation of tritiated fucose incorporation in rat wound explants from 10 pairs of rats revealed that a significant overall decrease in radiolabeled glycoprotein production of 23 percent occurred when putrescine was present; in addition, the fraction of tritiated glycoprotein which was soluble in buffer was significantly increased, while that in the buffer-insoluble fraction decreased. This study suggests that putrescine inhibits tissue transglutaminase-mediated cross-linking of fucoprotein in the extracellular wound matrix and supports a role for this process in the generation of incisional wound strength.

Transglutaminase levels in Dupuytren's disease.

By use of immunoperoxidase staining, tissue transglutaminase and aminopropeptide of collagen type III were localized to fibroblasts running within cords of Dupuytren's fascia. Quantitative analysis of transglutaminase revealed that activity levels were significantly higher in acutely contracting fascia than in chronic contractures. The results show that contractures in Dupuytren's fascia may be reflected by the level of transglutaminase activity in the tissue. Furthermore, it is suggested that isopeptide bond formation, involving collagen type III aminopropeptide moieties, may be the biochemical mechanism by which transglutaminase maintains the contracted state.

Plasma fibronectin levels as predictive of survival in major thermal injury.

Plasma fibronectin levels, assayed by rocket immunoelectrophoresis, were measured in adult burn patients with 25-75 per cent total body surface area burns. Significant differences in the level of plasma fibronectin were detected in the one fatally injured patient prior to death (at 48 and 24 h) as a precipitous and persistent drop to 0.07 and 0.09 g/l, respectively. This deficiency coincided with early clinical signs of sepsis, the severity of which was not clinically apparent prior to overwhelming sepsis and incipient shock. This report supports previous suggestions that secondary deficiencies in plasma fibronectin may be predictive of mortality occurring after day 6 postburn. The need for routine assay of plasma fibronectin using rocket immunoelectrophoresis is demonstrated.

Intrathoracic meningocele associated with neurofibromatosis: case report.

The authors present a case of intrathoracic meningocele associated with neurofibromatosis. Computed tomography with metrizamide myelography proved valuable in locating the lesion, thus facilitating surgical intervention. With the preoperative diagnosis established and the severity of the meningocele known, the surgeons safely employed a subpleural approach at thoracotomy.

Components of increased labelling with putrescine and fucose during healing of skin wounds.

To study the glycoproteins and transglutaminase substrates involved in healing, wounds were made in the skin of anesthetized rats with a biopsy punch. Explants made 1-5 days later were incubated with [3H]-labelled putrescine, fucose or proline. As compared with unwounded skin there was an increased incorporation of label which was greatest at 3 days. Incubation for various times suggests that the incorporation of fucose and proline is dependent on protein synthesis, whereas putrescine is incorporated into preformed proteins. Putrescine and fucose label polypeptides with an Mr of about 45,000 before and 14,000 after reduction. These correspond in size with the aminopropeptide of type III collagen. Other labelled material of higher molecular weight is partly degraded to similar polypeptides on collagenase digestion. Much of the [3H]putrescine in the polypeptides is in the form of gamma-glutamyl putrescine. It is hypothesized that isopeptide linkage of the aminopropeptide III occurs in wound healing.