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Biomedical subjects

L H Engrav

Publications and source records attributed to L H Engrav.

At least 19 recordsLinked to original sources

Transient exposure to tumor necrosis factor-alpha inhibits collagen accumulation by cultured hypertrophic scar fibroblasts.

BACKGROUND: Hypertrophic scars (HS) are frequent consequences of deep dermal injury, such as deep partial-thickness burns and abrasions, and are characterized by overproduction of collagen. In vitro studies have shown that cultured HS fibroblasts produce elevated levels of collagen and insulin-like growth factor-binding protein 3 (IGFBP-3). Additionally, histological studies have indicated HS contain fewer tumor necrosis factor alpha (TNF-alpha)-positive infiltrating cells and express lower levels of TNF-alpha mRNA, suggesting TNF-alpha, which can inhibit collagen expression in some systems, may function to deactivate the wound healing process in scars. HS also exhibit increased levels of transforming growth factor beta (TGF-beta), a factor that stimulates collagen and extracellular matrix deposition by fibroblasts and also stimulates IGFBP-3 expression. In some systems, IGFBP-3 mediates the effects of TGF-beta. The present study sought to determine the effects of continuous and transient TNF-alpha exposure on collagen and IGFBP-3 expression by cultured HS fibroblasts and to investigate the role of IGFBP-3 in collagen accretion by HS fibroblasts. MATERIALS AND METHODS: Superficial and deep dermal HS fibroblasts from four patients were cultured. Fibroblasts were cultured in serum-free medium and exposed to 0-2 ng/ml TNF-alpha for 0, 1, 4, or 72 h. After 72 h of culture, medium samples were processed for Western blot analysis of type I collagen accumulation or for ligand blot analysis of IGFBP-3 accumulation. The effects of an anti-IGFBP-3 neutralizing antibody on collagen accumulation were also assessed. RESULTS: Treatment of superficial and deep HS fibroblasts with TNF-alpha resulted in dose-dependent decreases in accumulation of both type I collagen and IGFBP-3 in the culture medium (P < 0.01). However, using the anti-IGFBP-3 neutralizing antibody, a causal relationship between decreased IGFBP-3 and decreased collagen accumulation could not be demonstrated. Transient exposure of cultured HS fibroblasts to TNF-alpha for as little as 1 h was as effective as continuous exposure to TNF-alpha for 72 h in inhibiting collagen accumulation. CONCLUSIONS: These results support the hypothesis that TNF-alpha functions as a wound healing deactivation signal that is deficient in HS. Although TNF-alpha inhibited accretion of both collagen and IGFBP-3, the role of IGFBP-3 in HS remains unresolved. This study suggests that transient TNF-alpha exposure may be used to inhibit collagen overaccumulation in HS and that the timing of TNF-alpha exposure following dermal injury may not be critical for this inhibition.

Adult

Methemoglobinemia secondary to topical silver nitrate therapy--a case report.

Methemoglobinemia is a rare complication in individuals exposed to nitrates or nitrites. Whereas methemoglobinemia is a recognized potential complication in burn patients treated with topical 0.5% silver nitrate solution, no report of methemoglobinemia in burn patients has been present in the literature for more than 15 years. We raise consciousness about this complication with a case report of a 12-month-old child with necrotizing fasciitis resulting from a cutaneous flank infection. The patient developed cyanosis 20 days after initiation of topical treatment with 0.5% silver nitrate solution. Intravenous injection of methylene blue can restore normal blood oxygenation.

Administration, Topical

Full-thickness grafting of acute eyelid burns should not be considered taboo.

Split-thickness skin grafts are commonly used for the treatment of acute eyelid burns; in fact, this is dogma for the upper lid. Ectropion, corneal exposure, and repeated grafting are common sequelae, almost the rule. It was hypothesized that for acute eyelid burns, the use of full-thickness skin grafts, which contract less than split-thickness skin grafts, would result in a lower incidence of ectropion with less corneal exposure and fewer recurrences. The records of all patients (n = 18) who underwent primary skin grafting of acutely burned eyelids (n = 50) between 1985 and 1995 were analyzed retrospectively. There were 10 patients who received full-thickness skin grafts (12 upper lids, 8 lower lids) and 8 patients who received split-thickness skin grafts (15 upper lids, 15 lower lids). Three of 10 patients (30 percent) who received full-thickness skin grafts and 7 of 8 patients (88 percent) who received split-thickness skin grafts developed ectropion and required reconstruction of the lids (p = 0.02). No articles were found substantiating the concept that only split-thickness grafts be used for acute eyelid burns. The treatment of acute eyelid burns with full-thickness rather than split-thickness skin grafts results in less ectropion and fewer reconstructive procedures. It should no longer be considered taboo and should be carried out whenever possible and appropriate.

Acute Disease

Limb-salvage in reconstruction of recalcitrant pressure sores using the inferiorly based rectus abdominis myocutaneous flap.

Pressure sore closure is frequently a reconstructive challenge. This challenge is particularly evident in cases of multiply recurrent sores. In such settings, there are often opportunities to manage the recurrent wounds either by repeated advancement of previous flaps or by design of alternative ones. However, these interventions are not always feasible, and limb amputation with total thigh flap closure must be considered. A review of operative experience with seven such complex pressure sores in seven patients is presented. Each patient had previously suffered a permanent thoracic-level spinal cord injury. Prior attempts at wound closure were unsuccessful. Despite consideration of all described locoregional flaps, no limb-sparing procedure could be designed satisfactorily. As an alternative to either hip disarticulation and total thigh flap coverage or distant free-tissue transfer, we reconstructed the debrided ulcer beds with inferiorly based rectus abdominis myocutaneous flaps. Six of the seven wounds healed primarily, whereas one required repeated debridement and the addition of a gracilis muscle flap to achieve complete closure. Postoperative follow-up has ranged from 6 to 45 months. Each patient has returned to his baseline preoperative activity level with no clinical compromise of abdominal wall function. All wounds have healed. Successful application of the inferiorly based vertical rectus abdominis myocutaneous flap for cases of both recalcitrant ischial and trochanteric pressure sores is demonstrated and its consideration is advocated if no reconstructive options short of extremity amputation and total thigh flap coverage exist for such challenging sores.

Activities of Daily Living

Results of 268 pressure sores in 158 patients managed jointly by plastic surgery and rehabilitation medicine.

Despite improvements in surgical repair of pressure sores, recurrence rates greater than 80 percent are reported, thus indicating that this difficult problem is not yet solved. Recurrence results in additional hospitalizations and increased medical expenses. Because associated general clinical and social issues are numerous for these patients, our physical medicine and rehabilitation colleagues are active participants in their perioperative medical care. In addition, the Department of Physical Medicine and Rehabilitation also directs a complete postreconstruction rehabilitation and education program for them. The results of surgically repaired pressure sores for patients managed in this collaborative fashion have not been previously reported. Pressure sore patients at the Harborview and University of Washington Medical Centers are evaluated by plastic surgery colleagues together with the Department of Physical Medicine and Rehabilitation. Patients believed to be candidates for complete postoperative rehabilitation are offered surgical repair and constitute this study cohort. Individuals who cannot cooperate with our protocol are treated nonoperatively and are not included in this study. A retrospective analysis of all 158 patients (mean age 34.5 years) operated on for 268 grade III and IV pressure sores between October of 1977 and December of 1989 was performed. Following surgical debridement and reconstruction, patients receive their principal medical care from the Department of Physical Medicine and Rehabilitation service while the Plastic Surgery Department manages the surgical wounds. Graduated patient mobilization is initiated in accord with a mutually agreed upon standardized protocol. New or primary sores numbered 174 (65 percent), and recurrent or secondary sores numbered 94 (35 percent). Mean patient follow-up was 3.7 years. The overall pressure sore recurrence rate (recurrence at the same site) was 19 percent, and the overall patient recurrence rate (previous patient developing a new sore) was 25 percent. Recurrence rates of 22 and 15 percent were noted for primary and secondary pressure sores, respectively. On most recent examination, 131 patients (83 percent) had intact pelvic and perineal skin. These results support a collaborative approach to the management of high-grade pressure sore patients. Our protocol of mutual patient evaluation followed by surgical reconstruction and postoperative rehabilitation yields notably low recurrence rates of both primary and secondary sores. In addition, the high percentage of patients who manifest long-term maintenance of skin integrity demonstrates the excellent education in personal skin and self-care that this approach provides. Not only do patients enjoy successful and durable reconstructive results, but additional hospitalizations and health care expenses implicit to pressure sore recurrence are consequently diminished. This collaborative clinical effort remains our standard of care.

Adult

Pressure sores in the acute trauma patient: incidence and causes.

OBJECTIVES: The purpose of this review was to determine the incidence of pressure sores in acute trauma patients and to identify the causes. DESIGN AND MATERIALS AND METHODS: This study is a retrospective chart review of all acute trauma patients admitted to Harborview Medical Center between January of 1991 and December of 1993 who were discharged with an ICD-9 diagnosis of acute pressure sore. RESULTS: A total of 7,492 trauma patients were admitted. Thirty-two patients developed 44 pressure sores for an incidence of 0.4%. All of the patients were severely injured (mean Injury Severity Score, 21). Eighteen (41%) of the pressure sores developed as a result of unrelieved positional pressure. Thirteen (30%) of the pressure sores were equipment induced. CONCLUSION: Our incidence of pressure sores in acute trauma victims is very low and occurs in those most seriously injured. The majority of the wounds are due to unrelieved pressure from body positioning or equipment failure.

Adult

Reducing the period of immobilization following pressure sore surgery: a prospective, randomized trial.

The cost to care for a patient with pressure sores can be exorbitant. One part of this expense results from the prolonged postoperative immobilization. Published protocols report 3 to 8 weeks of immobilization; however, there are no studies that establish longer periods to be superior. To justify our 3-week protocol, we conducted a prospective, randomized trial of 2 versus 3 weeks of postoperative immobilization. Each patient was randomized preoperatively to either 2 or 3 weeks of postoperative immobilization. A total of 42 patients with a diagnosis of paraplegia, tetraplegia, or multiple sclerosis and a solitary pressure sore were enrolled over 5 years. The complication rates in the two groups (9 of 23, or 39 percent, for the 2-week group and 9 of 19, or 47 percent, for the 3-week group) were not statistically different (p < 0.493). However, the time to mobilization was significantly reduced in the 2-week group (16.1 +/- 6.1 versus 22.9 +/- 4.9 days, p < 0.0003), as was the time to achieve sitting (21.2 versus 28.9 days, p < 0.0026). In summary, 2 weeks of postoperative immobilization following surgery is adequate for uncomplicated solitary pressure sores.

Humans

Differential expression of IGFBPs by normal and hypertrophic scar fibroblasts.

Insulin-like growth factor-I (IGF-I) is a potent fibroblast mitogen which influences wound healing. IGF action is regulated by a family of six IGF-binding proteins (IGFBPs). The purpose of this study was to determine if expression of IGFBPs is altered in hypertrophic scarring, a wound-healing condition commonly associated with deep dermal injury. Fibroblast populations from the superficial and deep dermal layers of normal human skin (SN and DN, respectively) and from superficial and deep layers of hypertrophic scars (SSc and DSc, respectively) were established and cultured in serum-free medium with or without several growth factors known to modulate wound healing, including basic fibroblast growth factor, the BB isoform of platelet-derived growth factor, IGF-I, and transforming growth factor-beta (TGF-beta). IGFBP release was analyzed by radioligand blot assays of culture media. Two main forms of IGFBPs were released, IGFBP-3 and a 24-kDa form which comigrated with serum IGFBP-4. DSc fibroblasts accumulated significantly more IGFBP-3 into serum-free culture medium than did SN, DN, or SSc fibroblasts in all conditions except TGF-beta treatment and confluence. Additionally, comparisons of IGFBP-3 release by each cell type with and without TGF-beta revealed TGF-beta stimulated IGFBP-3 accumulation by SN and DN fibroblasts but not by SSc or DSc fibroblasts. DN and DSc fibroblasts accumulated significantly more of the 24-kDa IGFBP species than SN or SSc fibroblasts in all conditions except TGF-beta or IGF-I treatment. These findings indicate that superficial and deep dermal fibroblasts are heterogeneous with respect to IGFBP release, and suggest that hypertrophic scar fibroblasts may represent a population of cells with regulatory properties distinct from those of normal dermal fibroblasts.

Cell Count

Necrotizing soft tissue infections: obstacles in diagnosis.

BACKGROUND: This study was done to identify obstacles in the early diagnosis and treatment of necrotizing soft tissue infections. STUDY DESIGN: A ten-year retrospective case series was analyzed. RESULTS: Data from 29 patients were analyzed. Among patients undergoing early operation within 24 hours of admission (n = 17) there was one death (6 percent mortality rate); survivors averaged 2.9 operations per patient. By comparison, of patients with delayed operation (n = 12) three died (25 percent mortality rate) and there were 3.6 operations per patients. Positive fine-needle aspiration (FNA) of suspicious lesions, demonstrating either pus or bacteria by Gram's stain, led to early operation in 80 percent of patients tested. Patients with soft tissue gas on radiographs were more likely to undergo early operation (58 percent). Delayed operation was more common in the absence of radiographic findings. All patients admitted to nonsurgical services had delayed operations. CONCLUSIONS: Suspected necrotizing soft tissue infections require prompt surgical evaluation and early operative exploration. Early operation with definitive surgical therapy initiated within 24 hours of admission is associated with decreased mortality rates. Negative FNA findings, nondiagnostic radiographs, and admission to a nonsurgical service correlate with delay in definitive operative intervention.

Adolescent

Platelet-derived growth factor and wound contraction in the rat.

This experiment was undertaken for three purposes: (1) to determine a dose-response curve of acute steroid inhibition of wound contraction in the rat; (2) to confirm the results of our preliminary study that platelet-derived growth factor (PDGF) enhanced wound contraction in acutely steroid impaired rats; and (3) to examine the histology of the PDGF-treated wounds. To determine the dose-response of acute steroid inhibition of wound contraction, the rats were suppressed with daily doses of methylprednisolone and wound contraction was measured. Results demonstrated that significant glucocorticoid-induced inhibition of wound contraction begins with daily methylprednisolone doses of 2.0 mg/wound/day or 6.7 mg/kg/day. In an effort to confirm the results of our previous study of the effect of PDGF on wound contraction in acutely steroid-impaired rats and to study the histology of the PDGF-treated wounds, rats were suppressed with methylprednisolone or hydrocortisone and administered daily topical doses of rPDGF-BB. Wound contraction measurements revealed no improvement in the amount or rate of wound contraction. Histologically, the wounds were all very similar in the patterns of cellularity, granulation tissue maturity, collagen content, and epithelial migration. We have clarified the dose response of acute steroid inhibition of wound contraction in rats, data previously unavailable, and have concluded that PDGF in reasonable doses does not improve wound contraction in steroid-impaired rats nor does it alter the histology of the wounds.

Animals

Changes in transfusion practices in burn patients.

In 1980 patients with burns greater than 10% of total body surface area (TBSA) received a mean of 8 units of blood (range, 0-42 units) during hospitalization in our burn center. Concern about the risks of blood transfusion caused us to reassess our transfusion practices and to question the need to maintain hematocrits above 30%. We compared the quantity of blood given to burn patients at Harborview Medical Center in 1980 with that given in 1990. Available records were reviewed from all patients with greater than 10% TBSA burns who required at least one operation (1980; n = 41; 1990: n = 38). There were no differences between groups for patients' ages, timing of first excision, or length of hospital stay. There were no differences in extent of burn excision per operation, but surgical times were significantly shorter in 1990 than in 1980. In 1980, 1.2 +/- 1.2 mL of blood was transfused per square centimeter surface area excised, compared with 0.23 +/- 0.49 mL in 1990 (p < 0.0001). In 1980, 133 +/- 153 mL blood was transfused per patient per percent burn during the acute hospitalization, compared with 20 +/- 34 mL in 1990 (p < 0.0001). There have been no instances of myocardial infarction or congestive heart failure related to the maintenance of lower hematocrits. We now permit hematocrits to fall to 15%-20% in healthy patients who need limited operations. In healthy patients with more extensive burns we accept hematocrits of 25%, and only critically ill patients and those with pre-existing cardiovascular disease are transfused to hematocrits of 30% or higher.

Adolescent

Engine block burns: Dupuytren's fourth-, fifth-, and sixth-degree burns.

We recently treated two patients with engine block-muffler contact burns and greatly underestimated the devastating injuries to bone, deep fascia, and muscle. As a result, each patient required multiple procedures to close their burn wounds. Ten-year data from the University of Washington Burn Unit confirmed our observation that these burns tend to be considerably deeper than suspected. Eighteen patients with contact burns from engine parts were identified from 1980 through 1990. Nine (50%) of these were initially recognized to be fourth-degree and five (28%) were third-degree thermal injuries, showing that these are deep burns. Eight patients required fascial excisions and four required debridement of devascularized bone. The mean burn size was only 6% total body surface area; however, the patients with fourth-degree burns had an average graft take of only 56% and required a mean hospital stay of 44 days. Patients with third-degree burns also had suboptimal graft take and some required prolonged hospitalization. Thirty-six percent of patients required flaps either as the initial procedure or as a second procedure following an autograft. The four patients with partial-thickness burns healed without surgery and their average length of hospital stay was 3 days. Of the entire group, only four healed without surgery and only five healed with a single operation. Our 10-year data indicate that engine block contact burns are usually small, but most are deceptively deep, involving tendon, muscle, or bone. If the burn appears full thickness, suspicion must be very high at the initial surgical procedure that there is deep tissue destruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Traffic

Early ambulation and discharge in 100 patients with burns of the foot treated by grafts.

Traditional treatment after grafting of foot, ankle, and lower leg burns is bedrest, limb elevation, and gradual ambulation only after 5 to 10 days. In 1982 we suggested that aggressive surgical treatment and early ambulation could shorten hospital stay and decrease morbidity. Our treatment of these burns is excision and grafting, application of an Unna (dome paste) boot immediately in the operating room or the next morning, with normal ambulation 4 hours later and discharge of the patient if there are no other reasons for continued hospitalization. This paper reports the continuation of this plan in 100 patients treated since 1982 with a mean age of 28.8 +/- 16.9 (SD) years and burn size of 3.7% +/- 4.4%. Sheet grafts were applied to 64% with a 96% take and narrowly meshed grafts to 36% with a 97% take. Results were excellent in 85 patients, satisfactory in ten, and poor in three who required another graft. Return to work was in 4.7 +/- 3 weeks. Unna boot application permits immediate ambulation, avoids frequent dressing changes, permits a brief or no hospital stay, and provides excellent graft take with prompt return to work.

Administration, Topical

Hook nail deformity repaired using a composite toe graft.

The hook nail deformity is caused by loss of fingertip bone and soft tissue. Healing can result in a volarly displaced distal nailbed and a tight tip with inadequate padding and a poor cosmetic appearance. A composite graft from the second toe placed beneath the released nailbed gives good support and improved pulp substance. The technique of the composite toe graft has been performed in nine patients. All grafts were 100 percent viable, but one patient required a second graft for additional tip bulk. There has been no donor-site morbidity in the follow-up of 1 month to 2 years.

Adult

Rating burn impairment.

We have described the method of rating impairment published by the American Medical Association (AMA) and the method requested by the Social Security Administration (SSA). For various reasons it will be some time before burn centers will be able to report impairment as easily as they now report length of stay and other parameters, but in time it will come. When it is possible, the methods used will probably not be identical with the AMA method nor the SSA method described previously. But whatever method is used, it will surely incorporate concepts from each and portions of each--and the two exist and are used right now. Therefore, it is useful for burn physicians to understand the two methods and be prepared to use either.

American Medical Association

Treatment of the concrete scalp donor site.

The scalp has become a popular donor site for split-thickness skin, and few complications have been reported. However, we have been troubled by 5 patients in whom the donor site did not epithelialize but rather turned into dried granulation tissue with embedded growing hairs, a situation rather like concrete with steel reinforcing rods. The pathophysiology is not clear but seems to be related to thick grafts from hair-bearing areas. We treated the lesions by removing the granulation tissue, shaving the hair, and treating the wound as a new donor site. Four lesions healed with total or near total regrowth of hair, and one required a small skin graft.

Adolescent

Outcome and treatment of electrical injury with immediate median and ulnar nerve palsy at the wrist: a retrospective review and a survey of members of the American Burn Association.

Electrical injury to the upper extremity with immediate median and ulnar nerve palsy at the wrist is uncommon but devastating. When it does occur, the immediate clinical questions are (1) will the nerves recover, and (2) should the carpal tunnel and Guyon's canal be released? Our review of the literature did not answer these two questions. Therefore, we reviewed our experience with such patients and surveyed approximately 10% of the physician members of the American Burn Association. We reviewed approximately 80 patients with electrical injuries treated between January 1983 and September 1988, and found 5 patients (8 extremities) who did not require amputation and who manifested immediate palsy of the median and ulnar nerves at the wrist. The questionnaire was returned by 83% of those contacted. We concluded that such nerve palsies can recover to a significant degree and that a majority of surgeons would release the carpal tunnel and Guyon's canal, expecting improved recovery. Although it is still not proven whether decompression is beneficial, we will continue to decompress the carpal tunnel and Guyon's canal in such circumstances.

Adult