Inhibition of wound contraction with locally injected lathyrogenic drugs.

BACKGROUND: Previous studies using systematically administered lathyrogens to inhibit wound contractures have produced inconsistent results. The purpose of this study was to investigate the effects of lathyrogenic drugs on wound contraction when injected locally. METHODS: Two symmetrical full-thickness wounds were made on the dorsum of either side of hairless (hr/hr) mice; thus, each animal served as its own control. Animals were divided into groups receiving daily local injections of beta-aminopropionitrile or D-penicillamine, or both beta-aminopropionitrile and D-penicillamine and normal saline vehicle (control side) for 5 or 10 days. The rate of contraction was determined by serial measurements of the surface area of each wound during the treatment period. At the end of the treatment period, the wounds were excised en bloc with the chest wall and prepared for blinded histological analysis. Granulation tissue thickness, number of fibroblasts in granulation tissue per unit area, number of inflammatory cells (neutrophils, lymphocytes, macrophages and mast cells) in subjacent muscle per unit area, and collagen deposition in subjacent muscle were determined. RESULTS: Wound contraction, granulation tissue thickness, and collagen deposition in subjacent muscle were decreased only in wounds treated with beta-aminopropionitrile plus D-penicillamine. Collagen deposition in subjacent muscle was also decreased in wounds treated with D-penicillamine alone. Neither drug alone nor the combination affected the number of inflammatory cells in subjacent muscle. Body weight was not affected by the experimental procedures. CONCLUSIONS: The combination of beta-aminopropionitrile and D-penicillamine is potentially useful for inhibiting contracture formation when injected locally.

Inhibition of wound contraction with colchicine and D-penicillamine.

The effects of locally injected combined colchicine and D-penicillamine on wound contraction were investigated in a murine model. Two full-thickness excisional wounds were made on either side of the back of hairless (hr/hr) mice. A volume of 0.15 ml of colchicine, D-penicillamine, or combined colchicine and D-penicillamine in normal saline vehicle were injected daily into the wound on one side of the animal and 0.15 ml of vehicle alone was injected into the wound on the other side for 5 or 10 days; thus, each animal served as its own control. The surface area of each wound was measured on Days 0, 5, and 10 to determine an index of the rate of wound contraction. At the end of the experimental period (Day 5 or 10), wounds were excised en bloc from euthanized animals for histological studies. The following histological parameters were determined: the thickness of the granulation tissue, the number of fibroblasts in granulation tissue per unit area, and the number of inflammatory cells (neutrophils, lymphocytes, macrophages, mast cells) in subjacent muscle per unit area. Our data showed that after 5 days of treatment, wound contraction was significantly inhibited only in wounds treated with combined colchicine and D-penicillamine. Wound contraction was significantly inhibited even after 10 days of treatment with the combination. Histological studies revealed that although the thickness of the granulation tissue and the number of inflammatory cells in subjacent muscle were decreased by D-penicillamine alone, only combined colchicine and D-penicillamine decreased the thickness of the granulation tissue, fibroblasts in granulation tissue, and inflammatory cells in subjacent muscle. Our data suggests that very low concentrations of colchicine and D-penicillamine when combined and injected locally may be potentially useful in controlling surface scar formation.

Comparison of the effects of commonly used wound agents on epithelialization and neovascularization.

BACKGROUND: The primary effect sought with most topical wound therapy is antimicrobial. Topical wound agents are thought to promote normal healing by protecting the wound from infection. In this study, we examined the effect of six commonly used topical wound agents (bacitracin, sodium hypochlorite, silver nitrate, silver sulfadiazine, mafenide acetate, and povidone-iodine) on epithelialization and neovascularization in noninfected wounds. For this study, a new wound model was used in which direct visualization and quantification of wound epithelialization and neovascularization were carried out throughout the entire healing process. STUDY DESIGN: We measured the effect which 500 U per g of bacitracin, 0.25 percent of sodium hypochlorite, 0.5 percent silver nitrate, 1 percent silver sulfadiazine, 8.5 percent mafenide acetate, and 10 percent povodione-iodine had on the rate of wound epithelialization and neovascularization. The agents were applied topically to 99 circular full-thickness wounds (2.25 mm diameter, 0.125 mm depth) created on the dorsum of male hairless mouse ears. This model enabled us to visualize and measure directly wound epithelialization and neovascularization repeatedly throughout healing, using intravital video microscopy and computerized digitized planimetry. RESULTS: Control wounds and wounds treated with silver sulfadiazine (n = 18) and mafenide acetate (n = 14) epithelialized in 7.2 +/- 0.7, 7.1 +/- 0.3, and 7.3 +/- 0.3 days, respectively. This was significantly (p < 0.01) faster than the wounds treated with povidone-iodine (n = 10), sodium hypochlorite, (n = 8), and bacitracin (n = 13). Wounds treated with povidone-iodine epithelialized the slowest (11.8 +/- 0.55 days). Wound neovascularization was completed most rapidly in the groups treated with povidone-iodine and silver sulfadiazine (15.0 +/- 0.4 and 15.3 +/- 0.7 days, respectively). This was significantly (p < 0.05) faster than wounds treated with silver nitrate (n = 15), which neovascularized in 18.4 +/- 0.56 days. One-half of the wounds treated with sodium hypochlorite (eight of 16) did not epithelialize or neovascularize. CONCLUSIONS: The various antimicrobial agents studied in our in vivo model affect wound epithelialization and neovascularization differently. These effects on these two very important aspects of healing should be taken into consideration when indicating a specific agent for treatment of different types of wounds.

The hairless mouse ear: an in vivo model for studying wound neovascularization.

Microvascular ingrowth into damaged tissue is an essential component of the normal healing process. In fact, wound therapy is often aimed at promoting neovascularization. However, little is known about the mechanisms that regulate microvascular ingrowth into a healing wound. This limited knowledge is largely due to the lack of adequate models in which microvascular ingrowth can be quantitatively analyzed throughout the healing process. To address this deficiency, we developed a model in which a wound was created on the ear of the hairless mouse-a well established model for directly viewing and measuring skin microcirculation. While the animals were under ketamine and xylazine anesthesia, 2.25 mm diameter full-thickness wounds were created on the dorsum of hairless mouse ears down to but not including the cartilage (0.125 mm depth). With the use of video microscopy and computer-assisted digitized planimetry, the precise epithelial and neovascular wound edge was viewed and measured regularly throughout healing. Therefore, this model can provide objective data on wound epithelialization and neovascularization throughout healing. This model was used to examine the effect of topical wound agents on epithelialization and neovascularization. Differential effects by these anti-microbial agents on these two processes were observed, which suggests clinical implications for their use.

Direct visualization and measurements of wound neovascularization: application in microsurgery research.

Neovascularization or angiogenesis is an essential yet poorly understood component of the healing process. In wound healing research, there is a lack of models enabling quantitative and continuous measurements of wound neovascularization. The hairless mouse ear wound model permits quantitative measurements of wound epithelialization and neovascularization continuously throughout the healing process. On the ears of male homozygous (hr/hr) hairless mice, standardized circular full thickness dermal wounds are produced; then, using vital microscopy, these two processes are directly viewed and measured at day 0 and every third day thereafter until these are complete. This model system and its application to clinically relevant situations are reviewed.

A randomized prospective study of topical antimicrobial agents on skin grafts after thermal injury.

We prospectively studied 52 consecutive patients who were treated by early tangential excision and grafting following thermal injury. The usefulness of two topical antimicrobial agents--0.5% silver nitrate (Ag) and neomycin (1 gm/liter) plus bacitracin (50,000 units/liter) (NB)--was compared with the effectiveness of Ringer's lactate (RL) for prevention of autogenous skin-graft loss due to infection. Graft loss of 10 percent or more occurred in 17 patients (33 percent)--due to infection in 16. Skin-graft loss was a minor problem in patients with less than 20 percent total body surface area (TBSA) burn (Ag: 0 of 6, NB: 1 of 6, RL: 1 of 5). The use of either antimicrobial (Ag or NB) resulted in less graft loss (1 of 14) than RL (4 of 6; p less than 0.05) in the 20 to 40 percent TBSA burn group. Large burns (greater than 40 percent) had a very high incidence of at least 10 percent graft loss (67 percent) regardless of treatment. Infection in the area of graft loss was caused by antibiotic-resistant organisms or yeast in 50 percent of the Ringer's lactate group and the entire neomycin plus bacitracin group. No graft infections were caused by resistant organisms or yeast in the silver nitrate group. This study demonstrates that topical antimicrobial agents reduce infection-related skin-graft loss in patients with medium-sized (20 to 40 percent TBSA) burns and that neomycin plus bacitracin is associated with rapid emergence of drug-resistant organisms whereas silver nitrate is not.

V-Y advancement flaps. Reusable flaps for pressure ulcer repair.

V-Y advancement modification of skin paddle design for the biceps femoris, tensor fascia lata, transverse lumbar, and gracilis flaps permits readvancement of each of these flaps for recurrent pressure ulcers. Our use of this refinement of these flaps over the past twelve years shows that up to two readvancements of each of these flaps can be done, thus preserving reconstructive options in a patient population prone to pressure ulcer recurrence.

One-stage simple mastectomy with immediate reconstruction for high-risk patients. An improved technique: the biologic basis for ductal-glandular mastectomy.

The heterogeneity of human breast carcinoma appears to be a cumulative interrelationship of genetic and environmental factors that may be identifiable with a high risk for carcinogenesis. Until breast cancer prevention is realized, one-stage total ductal-glandular mastectomy with immediate reconstruction may be offered as an alternative to simple mastectomy for women at high risk for developing cancer. This technique affords the complete extirpation of breast tissue at a deep plane with flaps that are identical in thickness to those elevated in classic mastectomies for invasive cancer. Breast reconstruction with submuscular prostheses in a one-stage procedure gives an aesthetically acceptable result. The role of ductal-glandular mastectomy as prophylaxis for invasive carcinoma warrants future prospective trials.

An ideal stent for reliable and efficient skin graft application.

A simple, efficient, yet expedient method producing an ideal stent has proved to be highly reliable in over 150 clinical cases. When performed technically correctly, 100% graft take may be anticipated under most grafting circumstances. The method uses Reston (3-M Company, St. Paul, MN), a synthetic urethane foam pad, as the stent material. Reston has intrinsic compressibility; therefore, a consistent external pressure can uniformly be exerted within the effective physiological range needed to achieve graft take. The stent is stapled in position and does not depend upon the mechanical forces generated by tissue elasticity. Several advantages inherent to the method include rapid and efficient surgical application, ease of postoperative care, use in clean or contaminated wounds, and effective and reliable graft survival. The pitfalls of other techniques are avoided. An in vitro study demonstrated the magnitude of the physiological pressures (mm Hg) applied by the elasticity of Reston when stapled in a simulated wound.

One-stage pharyngoesophageal and oral mucocutaneous reconstruction with two segments of one musculocutaneous flap.

This report describes a one-stage technique that provides both cover and lining to mucocutaneous defects of the head and neck with either latissimus dorsi or pectoralis major musculocutaneous units that are split into anatomic segments to create two independent flaps from one musculocutaneous unit. In addition, this technique further refines reconstruction of pharyngoesophageal defects. Techniques of simultaneous mandibular reconstruction with vascularized bone carried on these same segmental flaps are also commented on.

The split latissimus dorsi myocutaneous flap.

Consistent proximal branching of the latissimus dorsi neurovascular anatomy permits surgical splitting of the myocutaneous unit into two flaps. Either or both branches of the split flap can be independently transferred. Experimental and clinical applications of this flap, which illustrate several of its uses and advantages, are presented. Applications include simultaneous provision of cover and lining flaps for head and neck reconstruction, motor transfers with split muscle branches, preservation of motor function in the flap donor site with one split muscle branch, and microvascular free tissue transfer of the branched flap or of individual branches.

The biceps femoris myocutaneous advancement flap: a useful modification for ischial pressure ulcer reconstruction.

We describe a modification of the biceps femoris myocutaneous flap for reconstruction of ischial pressure ulcer defects. In this modification, all neural and vascular pedicles are preserved and the flap is advanced into the ischial defect rather than transposed as described in the literature. With this method, no transferred tissue is lost. Besides ensuring good tissue survival, the flap preserves a maximum number of reconstructive options in the event of ischial pressure ulcer recurrence. These advantages make the biceps femoris myocutaneous advancement flap our first choice for reconstruction of ischial pressure ulcer defects.

Desmoplastic malignant melanoma: a case report.

A further case of desmoplastic malignant melanoma of the cheek is presented, bringing the total number of reported cases to 15. Its clinicopathological features and treatment are discussed.

Primary treatment of shotgun injuries to the face.

The treatment of close-range shotgun wounds to the face can be extremely difficult. Over the years, surgeons have progressed from the conservative approach of debridement and delayed reconstruction to that of immediate reconstruction. While the complex nature of these injuries requires treatment on an individual basis, the principles of conservative debridement, thorough wound cleansing, and primary replacement of soft-tissue defects will often result in a better functional and esthetic restoration in a shorter period of time. Five patients with shotgun facial wounds managed by individualized primary repair are discussed.

Pseudomonas ulceration of the cornea following major total body burn: a clinical study.

If periorbital or facial areas are involved in burn injury, the eyes must be given prophylactic care. The importance of these cases is not to point out the danger of corneal injury as a direct result of thermal trauma; rather, it is to emphasize the seriousness of corneal abrasions and the danger of subsequent Pseudomonas infection during convalescence of the postburn patient. Once the corneal epithelium is damaged, ulceration rapidly occurs and when infected with Pseudomonas aeruginosa presents one of the most difficult ophthalmologic situations. The convalescent burn patient is in jeopardy of corneal abrasion during general anesthesia for grafting or debridement. Neither of the patients who underwent anesthesia was noted to have corneal abrasion. Nor did either ectropion or lid contracture develop in the three patients described herein. Lid contracture may lead to corneal exposure and should be corrected by expeditious lid tarsorrhaphy. Once ulceration has occurred, as with these patients, corneal transplantation may be indicated.