Tissue-engineered skin in the healing of wound stumps from limb amputations secondary to purpura fulminans.

Currently wound treatment options of amputation stumps due to purpura fulminans include healing by secondary intention from wound debridement, split-thickness skin grafting, tissue and muscle flaps, plantar skin free transfer, skin expansion, artificial skin, and hyperbaric oxygen therapy. We saw a 6-month-old girl with purpura fulminans as a complication of meningococcemia. She developed necrosis of the distal extremities resulting in bilateral amputation of the lower limbs. Shortly thereafter the leg stumps also became necrosed and she underwent unsuccessful split-thickness grafts of lower limb ulcers. The patient's difficult-to-heal wounds made her an excellent candidate for treatment with tissue-engineered skin. At 10 months of age, this was applied to her previously nonhealing wounds. The tissue-engineered skin induced rapid healing of the patient's chronic amputation stump ulcers and provided her with substantial pain relief. In conclusion, tissue-engineered skin appears to be a potential beneficial treatment for chronic wounds in children with nonhealing amputation stumps.

The role of graftskin (Apligraf) in difficult-to-heal venous leg ulcers.

A relatively recent option for treating leg ulcers that have lasted longer than a month is to use living bilayered skin equivalent alongside cornerstone compression therapy. This article discusses Graftskin and considers its practical use.

Tissue-engineered skin. Current status in wound healing.

Tissue-engineered skin is a significant advance in the field of wound healing and was developed due to limitations associated with the use of autografts. These limitations include the creation of a donor site which is at risk of developing pain, scarring, infection and/or slow healing. A number of products are commercially available and many others are in development. Cultured epidermal autografts can provide permanent coverage of large area from a skin biopsy. However, 3 weeks are needed for graft cultivation. Cultured epidermal allografts are available immediately and no biopsy is necessary. They can be cryopreserved and banked, but are not currently commercially available. A nonliving allogeneic acellular dermal matrix with intact basement membrane complex (Alloderm) is immunologically inert. It prepares the wound bed for grafting allowing improved cultured allograft 'take' and provides an intact basement membrane. A nonliving extracellular matrix of collagen and chondroitin-6-sulfate with silicone backing (Integra) serves to generate neodermis. A collagen and glycosaminoglycan dermal matrix inoculated with autologous fibroblasts and keratinocytes has been investigated but is not commercially available. It requires 3 to 4 weeks for cultivation. Dermagraft consists of living allogeneic dermal fibroblasts grown on degradable scaffold. It has good resistance to tearing. An extracellular matrix generated by allogeneic human dermal fibroblasts (TransCyte) serves as a matrix for neodermis generation. Apligraf is a living allogeneic bilayered construct containing keratinocytes, fibroblasts and bovine type I collagen. It can be used on an outpatient basis and avoids the need for a donor site wound. Another living skin equivalent, composite cultured skin (OrCel), consists of allogeneic fibroblasts and keratinocytes seeded on opposite sides of bilayered matrix of bovine collagen. There are limited clinical data available for this product, but large clinical trials are ongoing. Limited data are also available for 2 types of dressing material derived from pigs: porcine small intestinal submucosa acellular collagen matrix (Oasis) and an acellular xenogeneic collagen matrix (E-Z-Derm). Both products have a long shelf life. Other novel skin substitutes are being investigated. The potential risks and benefits of using tissue-engineered skin need to be further evaluated in clinical trials but it is obvious that they offer a new option for the treatment of wounds.

Use of skin substitutes in dermatology.

The use of skin substitutes to treat acute and chronic wounds should continue to increase as newer products are developed. The goals for the future are to eliminate the need for autografting, eliminate the risk for transmission of disease, improve the shelf life and simplify storage requirements, improve cosmetic outcomes, and reduce cost. A number of researchers are also looking to incorporate gene therapy into skin substitutes.

Chronic venous insufficiency and venous leg ulceration.

UNLABELLED: Venous ulcers are the most common form of leg ulcers. Venous disease has a significant impact on quality of life and work productivity. In addition, the costs associated with the long-term care of these chronic wounds are substantial. Although the exact pathogenic steps leading from venous hypertension to venous ulceration remain unclear, several hypotheses have been developed to explain the development of venous ulceration. A better understanding of the current pathophysiology of venous ulceration has led to the development of new approaches in its management. New types of wound dressings, topical and systemic therapeutic agents, surgical modalities, bioengineered tissue, matrix materials, and growth factors are all novel therapeutic options that may be used in addition to the "gold standard," compression therapy, for venous ulcers. This review discusses current aspects of the epidemiology, pathophysiology, clinical presentation, diagnostic assessment, and current therapeutic options for chronic venous insufficiency and venous ulceration. (J Am Acad Dermatol 2001;44:401-21.) LEARNING OBJECTIVE: At the conclusion of this learning activity, participants should be familiar with the 3 main types of lower extremity ulcers and should improve their understanding of the epidemiology, pathogenesis, risk factors, clinical presentation, diagnostic assessment, and current therapies for chronic venous insufficiency and venous ulcers.

Purpura fulminans in a patient with malaria.

A case of purpura fulminans in a 44 year old woman infected with malaria is reported. The patient had laboratory findings consistent with disseminated intravascular coagulation and a severe eruption consisting of hemorrhagic bullae and crusts. This case is presented to elucidate another cutaneous manifestation of malaria.

Tissue-engineered skin (Apligraf) in the healing of patients with epidermolysis bullosa wounds.

BACKGROUND: At present, wound treatment of inherited epidermolysis bullosa (EB) is only supportive. OBJECTIVE: To determine the safety and clinical effects of tissue-engineered skin (Apligraf; Organogenesis Inc, Canton, Mass) in the healing of wounds of patients with different types of EB. DESIGN: An open-label uncontrolled study of 15 patients with EB treated with tissue-engineered skin. Each patient received tissue-engineered skin on up to 2 wounds on each of 3 clinic visits: day 1, week 6, and week 12. They were evaluated 7 (+/- 3) days and 6 weeks after each round of treatment. A quality-of-life survey was administered during week 6. SETTING: University of Miami, Miami, Fla. PATIENTS: Volunteers with EB. MAIN OUTCOME MEASURE: Safety and wound healing. RESULTS: A total of 69 different acute wounds received tissue-engineered skin at the day-1 (24 wounds), week-6 (23 wounds), and week-12 (22 wounds) visits. Overall, 63 wounds (79%) were found healed at the day-7 visit. Of the acute wounds, 82% (51/62) were healed 6 weeks after being treated, 75% (27/36) after 12 weeks, and 79% (11/14) after 18 weeks. Nine chronic wounds were also treated. Four were healed at 6 weeks; however, 7 were still open at the last clinic visit (week 18). There were no signs of rejection or clinical infection and no adverse events related to the tissue-engineered skin. The quality of life for most patients improved after treatment. Compared with patients' recollection of wounds treated with standard dressings, healing was faster and less painful. CONCLUSION: In this series of patients, tissue-engineered skin induced very rapid healing, was not clinically rejected, and was devoid of adverse effects. It was felt by the patients and families to be more effective than conventional dressings for EB wounds.

Skin grafting.

No longer an option of last resort, skin grafting has become a technique that is routinely and sometimes preferentially considered as skin replacement for burns, chronic ulcers, and skin defects after cutaneous surgical procedures. When selected as the best alternative for wound closure, autologous skin grafts are commonly considered the gold standard. Availability of autologous grafts is a major obstacle, however, and the search for a manufactured skin replacement has continued. In cases in which autologous grafts cannot be performed, skin substitutes have become an attractive alternative.

Angiographic embolization for intraperitoneal and retroperitoneal injuries.

Angiographic embolization (AE) has been used extensively for bleeding control after injuries to the face and neck. Its role in abdominal trauma requires further exploration. We reviewed the medical records of 137 consecutive patients who underwent angiography with the intent to embolize bleeding sites within the abdomen. Of them, 97 (71%) had blunt and 40 (29%) had penetrating trauma. AE was performed for hemorrhage associated with pelvic fractures (97 patients), liver lacerations (n = 26), renal lacerations (n = 12), splenic lacerations (n = 5), other injuries (n = 9), and multiple injuries (n = 12). On angiography, 102 patients were found to have bleeding sites and underwent AE, with angiographic and clinical bleeding control in 93 (91%). The rate of successful hemostasis by AE was identical in blunt and penetrating trauma patients. There was no major morbidity after AE. No factors predicted patients with a high likelihood to have a positive angiogram. Patients who had AE before or after a period of attempted hemodynamic stabilization in the intensive care unit were no different with respect to hemodynamic parameters immediately before AE or effectiveness of AE for bleeding control. AE is a safe and effective method for controlling bleeding after blunt and penetrating intra- and retroperitoneal injuries. Early AE may be used in selected patients as a front-line therapeutic intervention that offers expeditious hemostasis and prevents delays in definitive bleeding control.

Operative management of civilian rectal gunshot wounds: simpler is better.

Extraperitoneal rectal gunshot wounds have been managed with a variety of methods from simple diverting colostomy to combinations of rectal repair, proximal diversion, transperitoneal or presacral drainage, and distal bowel irrigation techniques. Treatment methodology is chosen based on anecdotal experience, and there is no clear evidence that any technique is superior to the others. The objective of this study was to compare 3 methods of managing civilian extraperitoneal gunshot wounds. Retrospective analysis of 30 consecutive patients with extraperitoneal rectal gunshot wounds was undertaken. Patients were treated with 1 of these 3 techniques: (1) simple diverting colostomy without rectal repair (group A, 12 patients); (2) diverting colostomy and rectal repair (group B, 12 patients); and (3) diverting colostomy and presacral drainage without repair (group C, 6 patients). Injury, hospital course, and outcome data were compared. The 3 groups were similar in age, injury severity, admission hemodynamics, preoperative and intraoperative time, blood loss, fecal contamination, and associated injuries. The overall incidence of complications was 27% (8/27): 25% (3/12) in group A, 33% (4/12) in group B, and 17% (1/6) in group C (p = NS). Complications directly associated with the rectal injury were found in 2 cases (7%): 1 group A patient developed a vesicorectal fistula and 1 group B patient developed a rectocutaneous fistula. For 10 patients with both rectal and bladder injuries, the complication rates for groups A, B, and C were 50%, 20%, and 0%, respectively (p = NS). No patient died. In conclusion, diverting colostomy without rectal repair or drainage appears to be safe for the management of most civilian retroperitoneal rectal gunshot wounds. Additional surgical maneuvers may be required for combined rectal and urinary trauma or other complex rectal injuries. Sound surgical principles, tailored to the individual case, should overrule any unproven dogmas.

Duration of antibiotic prophylaxis in high-risk patients with penetrating abdominal trauma: a prospective randomized trial.

To evaluate the effect of varying durations of antibiotic prophylaxis in trauma patients with multiple risk factors for postoperative septic complications, a prospective randomized trial was undertaken at an urban level I trauma center. The inclusion criteria were full-thickness colon injury and one of the following: (1) Penetrating Abdominal Trauma Index > 25, (2) transfusion of 6 units or more of packed red blood cells, or (3) more than 4 hours from injury to operation. Patients were randomly assigned to a short course (24 hours) or a long course (5 days) of antibiotic therapy. All patients received 2 g cefoxitin en route to the operating room and 2 g intravenously piggyback every 6 hours for a total of 1 day vs. 5 days. Sixty-three patients were equally divided into short-course (n = 31) and long-course (n = 32) therapy. This was a high-risk patient population, as assessed by the mean Penetrating Abdominal Trauma Index (33), number of patients with multiple blood transfusions (51 of 63; 81%), number of patients with an Injury Severity Score greater than 15 (37 of 63; 59%), number of patients with destructive colon wounds requiring resection (27 of 63; 43%), and number of patients requiring postoperative critical care (37 of 63; 59%). Differences in intra-abdominal (1-day, 19%; 5-days, 38%) and extra-abdominal (1-day, 45%; 5-days, 25%) infection rates did not achieve statistical significance. There continues to be no evidence that extending antibiotic prophylaxis beyond 24 hours is of benefit, even among the highest risk patients with penetrating abdominal trauma. A large, multi-institutional trial will be necessary to condemn this common practice with statistical validity.

The use of tissue-engineered skin (Apligraf) to treat a newborn with epidermolysis bullosa.

BACKGROUND: Inherited epidermolysis bullosa (EB) is a mechanobullous disorder. The Dowling-Meara variant, a subtype of EB, is characterized by widespread blister formation that may include the oral cavity and nails. Many patients with the Dowling-Meara phenotype are at increased risk of sepsis and death during infancy. The treatment of EB is generally supportive. The tissue-engineered skin used (Apligraf) is a bilayered human skin equivalent developed from foreskin. It is the only Food and Drug Administration-approved skin equivalent of its kind. It is approved for the treatment of venous ulcers of the lower extremities. It has also been used to treat acute wounds, such as graft donor sites and cancer excision sites. OBSERVATION: To our knowledge, we describe the first case in which a newborn with EB, Dowling-Meara variant, was treated with bilayered tissue-engineered skin. The areas treated with the tissue-engineered skin healed faster than the areas treated with conventional therapy. Most of the areas treated with tissue-engineered skin have remained healed, without developing new blisters. These areas appear to be more resistant to trauma. CONCLUSIONS: Our early success with tissue-engineered skin in this patient may have a significant impact on the future treatment of neonates with EB simplex. Future studies are needed to determine if the beneficial effects of tissue-engineered skin are reproducible in other neonates with EB simplex and in patients of all ages with different subtypes of EB.

Propylthiouracil hypersensitivity: report of two patients with vasculitis and review of the literature.

Two patients with a hypersensitivity vasculitis in association with propylthiouracil (PTU) administration are described. Although both patients presented with a cutaneous eruption, our first patient suffered severe systemic manifestations and the second patient's involvement was primarily limited to the skin. Patients with a vascular hypersensitivity reaction to PTU typically present with constitutional symptoms, acral purpuric skin lesions, and variable involvement of multiple organ systems. The reaction is treated by urgent withdrawal of PTU and implementation of supportive measures and immunosuppressive agents, as necessary. Prompt recognition of this condition and initiation of appropriate therapy lead to complete recovery in most cases.

Stimulation of collagen synthesis by the anabolic steroid stanozolol.

There is evidence that anabolic steroids, which are derived from testosterone and have markedly less androgenic activity, promote tissue growth and enhance tissue repair; however, the mechanisms involved in their anabolic activities remain unclear. In this report, we measured the effect of the anabolic steroid stanozolol on cell replication and collagen synthesis in cultures of adult human dermal fibroblasts. Stanozolol (0.625-5 microg per ml) had no effect on fibroblast replication and cell viability (p = 0.764) but enhanced collagen synthesis (p < 0.01) in a dose-dependent manner (r = 0.907). Stanozolol also increased (by 2-fold) the mRNA levels of alpha1 (I) and alpha1 (III) procollagen and, to a similar extent, upregulated transforming growth factor-beta1 (TGF-beta1) mRNA and peptide levels (p < 0.001). There was no stimulation of collagen synthesis by testosterone. The stimulatory effects of stanozolol on collagen synthesis were blocked by a TGF-beta1 anti-sense oligonucleotide, by antibodies to TGF-beta, and in dermal fibroblast cultures derived from TGF-beta1 knockout mice. We conclude that collagen synthesis is increased by the anabolic steroid stanozolol and that, for the most part, this effect is due to TGF-beta1. These findings point to a novel mechanism of action of anabolic steroids.

The safety and efficacy of a proteolytic ointment in the treatment of chronic ulcers of the lower extremity.

BACKGROUND: Elase is a widely used ointment consisting of a combination of 2 proteolytic enzymes, fibrinolysin and desoxyribonuclease (DNAse). It is said to promote debridement of necrotic and purulent debris from skin ulcers. OBJECTIVE: Our purpose was to assess the efficacy and safety of this ointment and its components in the treatment of chronic ulcers of the lower extremity. METHODS: This was a double-blind, randomized, prospective study of 84 patients with leg ulcers exhibiting necrotic and purulent debris, who were treated for 21 days with twice-daily applications of the ointment, fibrinolysin, DNAse, or who received the ointment vehicle (placebo). We assessed 6 efficacy features: ulcer size, purulent exudate, necrotic tissue, erythema, pain, and overall condition of the lesion at days 8, 15, and 21 after initiation of treatment. We also assessed the frequency of adverse effects. RESULTS: All treatments produced some improvement in the efficacy parameters and overall condition of the ulcers by week 3, but no statistically significant difference was found when compared with placebo. No serious adverse effects were noted. A later retrospective reanalysis of the data found a statistically significant reduction of purulent exudate only at days 3 and 7 of treatment in the group treated with the complete ointment, but not in the other features. CONCLUSION: The proteolytic ointment provides no long-term clinical benefit in reducing purulent exudate, pain, erythema, necrotic tissue, or overall condition of chronic leg ulcers when compared with either of its two components or placebo.

Double intussusception in an adult following a laparotomy for trauma: a case report and review of the literature.

Intussusception is an unusual occurrence in adults. Postoperative intussusception may represent a separate pathophysiologic entity from primary intussusception in adults, occurring more frequently in the small bowel and without a specific underlying cause. Surgical resection is not mandatory and in those patients with viable bowel in whom the intussusception can successfully be reduced, manual reduction alone is an appropriate surgical strategy. Intussusception after laparotomy for trauma is a recently recognized phenomenon. For as yet unexplained reasons there seems to be a high association with liver injuries. A case of double intussusception is presented after a penetrating injury to the liver with discussion of the possible etiology and pathophysiology of this entity.

Uncommon causes of ulcers.

Skin ulcers are a commonly encountered problem in clinical practice. Failure of an ulcer to respond to therapy might suggest less common causes of skin ulcers. This article reviews clinical aspects of uncommon skin ulcers.