Coronary angioplasty, bypass surgery, and retransplantation in cardiac transplant patients with graft coronary disease

BACKGROUND AND OBJECTIVE: Prior studies of laser tissue soldering (LTS) of epithelial skin have shown poor wound strength in the short-term; however, we hypothesize that greater tensile strength and healing properties will result from directing laser energy to the dermal aspect of the skin. The current study compares wound strength and histology in a rat skin flap model of epithelial and dermally applied LTS. STUDY DESIGN/MATERIALS AND METHODS: Skin flaps (2.5 x 4 cm) were raised and bisected on the dorsum of Sprague-Dawley rats. The center line of bisection was closed from a dermal approach by LTS (LTS-D, diode laser 15.9 W/cm2 + Columbia solder), the upper incision by epithelial LTS (LTS-E), and the lower incision by suturing (7-0 Vicryl). Wound skin strips (1-2 mm x 10 mm) were studied immediately (N = 14) and at 3 (N = 57), 7 (N = 31), and 10 (N = 28) days postoperatively and were subjected to tensiometric analysis. Histologic staining with hematoxylin and eosin and Mallory's trichrome methods were used to define wound architecture. RESULTS: No wound dehiscences were noted in any group. Greater immediate tensile strength was noted in wounds closed by LTS-D (521 +/- 61 g/cm2) versus LTS-E (342 +/- 65 g/cm2); however, this difference was not statistically significant (P = .08). By 3 days, both LTS-D (476 +/- 55 g/cm2) and LTS-E (205 +/- 37 g/cm2) maintained their initial strength; however, LTS-D and sutured (436 +/- 49 g/cm2) wounds were stronger (P < .05) than LTS-E. At 7 and 10 days, LTS-D (2,433 +/- 346 g/cm2 and 3,100 +/- 390 g/cm2) showed superior tensile strength (P < .05) compared to both LTS-E (1,542 +/- 128 g/cm2 and 2,081 +/- 219 g/cm2) and suturing (1,342 +/- 119 g/cm2 and 1,661 +/- 115 g/cm2). Histologic analysis of LTS-D wounds at 3 days showed full-thickness tissue apposition, complete epithelialization, and minimal inflammation or thermal injury. At 7 days, solder was present in the wounds. In contrast, LTS-E wounds at 3 days displayed lack of epithelialization secondary to thermal injury and partial-thickness tissue apposition. However by 7 days, epithelialization was complete with moderate scarring, and no solder was seen. Sutured samples appeared similar to LTS-D, except for poorer tissue apposition at the hypodermis. CONCLUSION: Our results show that skin flap wound healing after dermal LTS is superior to epithelial LTS and emphasizes the importance of site specificity in the utilization of this operative technique in reconstructive surgery.     

Changes in coronary risk profiles in employees after three years of multifactorial intervention

A mathematical model for computing stresses in sutured human skin wounds is presented. The model uses the incremental law of elasticity and elastic constants valid for in vivo orthotropic skin. The model is applied to compute the principal stress and displacements resulting from suturing small elliptical and circular wounds in a large flat sheet of skin, in order to determine the optimal suturing patterns. It is observed that the average stress index for a circular wound sutured toward the center is almost double that of a wound sutured transverse to the diameter. Thus, the latter type of suturing pattern is preferable. Similarly, suturing an elliptical wound transversely produces a lower average stress index than a circular wound of the same area. It is also found that the optimal ratio of semi-major to semi-minor axis of an elliptical wound is near 3 (for abdominal wounds), i.e., this ratio produces the most uniform stresses along the wound edges, where wound healing is slowest. Since high stresses have adverse effects on healing and blood flow, this work, depicting regions of high stresses, may be used along with other biological factors to help predict regions of slower healing in sutured wounds.     

The utilization of a biological adhesive for wound treatment: comparison of suture, self-sealing sutureless and cyanoacrylate closure in the tensile strength test

We produced a measurement apparatus for testing the tensile strength of wounds during cataract surgery, and tested the tensile strength of treated wounds including wounds sutured with various methods, non-sutured and wounds treated with various bio-tissue adhesives. METHODS: In cataract surgery on white rabbits eyes, a corneoscleral incision 5 mm in length was made 2.5 mm from the limbus corneae, and entry into the anterior chamber was obtained 0.5 mm to the clear cornea. After treatment for closure, the corneoscleral piece was subjected to the tensile strength test. RESULTS: The tensile strengths just after surgery were (1) 0 gf/mm2 after self-sealing sutureless closure; (2) 114 gf/mm2 after vertical suture closure (one stitch with 10-0 nylon); (3) 125 gf/mm2 after horizontal suture closure (one stitch with 10-0 nylon); (4) 143 gf/mm2 after infinity suture closure (with 10-0 nylon); (5) 112 gf/mm2 after fibrin glue (Beriplast P) application (instilled on the surface of scleral incision); (6) 121 gf/mm2 after fibrin glue application (glued on corneoscleral wound); (7) 131 gf/mm2 after cyanoacrylate closure (instilled on the surface of scleral incision); (8) 139 gf/mm2 after cyanoacrylate closure (glued on corneoscleral wound). The respective strengths at four days after surgery were: (1) 86; (2) 131; (3) 137; (4) 175; (5) 109; (6) 43; (7) 138; and (8) 108 gf/mm2. At 28 days after surgery, the respective strengths were (1) 164; (2) 167; (3) 184; (4) 209; (5) 322; (6) 195; (7) 251; and (8) 175 gf/mm2. CONCLUSION: The use of fibrin glue in treatment of a wound in cataract surgery is beneficial in assisting this treatment.     

Human albumin solder supplemented with TGF-beta 1 accelerates healing following laser welded wound closure

BACKGROUND AND OBJECTIVE: We examined the possibility that human albumin solder can be used as a vehicle for site specific delivery of growth factors for the purpose of accelerating tissue repair following laser welded wound closure. Certain human recombinant growth factors have been shown to accelerate wound healing in model systems. Pilot in vitro studies have established that several growth factors, including TGF-beta 1, maintain bioactivity following exposure to temperatures achieved during laser tissue welding. Using a temperature controlled laser delivery system (TCL) to precisely maintain welding temperatures, it is now possible to avoid thermal denaturation of exogenous bioactive molecules such as growth factors. STUDY DESIGN/MATERIALS AND METHODS: HB-EGF, bFGF, and TGF-beta 1 were tested in vitro for maintenance of bioactivity after exposure to 80 degrees C. In vivo experiments using porcine skin determined the efficacy of solders augmented with growth factors. Incisions were repaired using human albumin alone or supplemented with HB-EGF (2 micrograms), bFGF (10 micrograms), or TGF-beta 1 (1 microgram). Wounds were excised at 3, 5, and 7 days post-operatively. Tensile strength, total collagen content, and histology were performed. RESULTS: At 3 days, tensile strength (TS) of TGF-beta 1 wounds were 36% (P < 0.05) and 20% (n.s.) stronger than laser alone and suture closures, respectively. By 5 days the TS of the TGF-beta 1 group increased by 50% (P < 0.05) and 59% (P < 0.02) over laser alone and suture groups, respectively. At 7 days the TGF-beta 1 group was 50% (P < 0.05) and 79% (P < 0.01) stronger than laser solder alone or suture, respectively. The HB-EGF and bFGF groups were equivalent to the laser solder group at all time points. Total collagen TGF-beta 1 Accelerates Healing Following Laser Welding content at 7 days increased in the TGF-beta 1 group by 7% (n.s.) over the suture group and 21% (P < 0.05) in the laser group. CONCLUSION: Human albumin solder supplemented with TGF-beta 1 increases the early post-operative strength of laser welded wounds. This novel application of laser tissue soldering augmented with a growth factor has the potential to bring about immediate fluid tight seals while providing site specific delivery of biological modifiers. This may lead to an overall improvement in post-operative convalescence, wound infections, and hospital costs.     

MRI of the intracerebral lesions at 0.5 Tesla: comparison of fast spin-echo and conventional spin-echo sequences

The purpose of this study was to identify the angiosome of the medial saphenous artery and vein and to evaluate the use of this cutaneous angiosome as a free skin flap in the dog. In phase 1 of this study, selective angiography of the medial saphenous artery performed in six canine cadavers showed that the skin covering the entire medial femorotibial area, the distal half of the caudal head of the sartorius muscle, and the gracilis muscle were perfused by the medial saphenous artery. In phase 2, a medial saphenous fasciocutaneous island flap was raised and sutured back to the skin edges of the donor wound in three dogs. One hundred percent survival of all of the flaps occurred. In phase 3, a medial saphenous fasciocutaneous microvascular free flap was transferred to a wound that was created over the dorsal metacarpal (n = 3) or metatarsal region (n = 3). The mean length +/- SD of the medial saphenous vascular pedicle was 80 +/- 13 mm (n = 5); the mean diameter +/- SD of the medial saphenous artery was 2.8 +/- 0.2 mm (n = 5) and the mean diameter +/- SD of the medial saphenous vein was 4.2 +/- 0.2 mm (n = 5). One hundred percent of all flaps survived (n = 6). Selective angiography or the distal cranial tibial artery (metatarsal wounds, n = 3) and the median artery (metacarpal wound, n = 3) was performed 3 weeks after surgery. All of the vascular anastomoses were patent and neovascularization of the wound beds was present. This free flap was found to be acceptable for cosmetic reconstruction of wounds located on the distal extremity.     

Medial prefrontal lesion deficits involving or sparing the prelimbic area in the rat

OBJECTIVE: Evaluate wound healing of incisions created by the scalpel, electrocautery, CO2 laser, and potassium titanyl phosphate (KTP) laser in the upper aerodigestive tract in an animal model. STUDY DESIGN: Prospective randomized study in an animal model. METHODS: Postoperative oral intake, histologic depth of injury, and tensile mechanical strength were measured in rat tongues after creating incisions using a scalpel, electrocautery, CO2 laser, and KTP laser. An unpaired, two-tailed Student's t-test was used to compare results between the experimental groups. RESULTS: Oral intake, indirectly assessed by postoperative weight loss, by the third postoperative day was significantly decreased in the electrocautery (P = 0.004), CO2 laser (P = 0.001), and KTP laser (P = 0.0001) groups as compared with the scalpel group. The depth of the wound healing, as assessed by histologic examination, was successively greater for the scalpel (75 +/- 13 microm), electrocautery (110 +/- 10 microm), CO2 laser (145 +/- 10 microm), and KTP laser (195 +/- 23 microm) groups. However, this difference was only statistically significant for the CO2 laser (P = 0.006) and KTP laser (P = 0.01) groups relative to the scalpel group. Wounds created by the KTP laser had the lowest strength (76.5 +/- 6.9 kPa) as compared with the CO2 laser (156 +/- 28.4 kPa), electrocautery (153 +/- 15.7 kPa), and scalpel groups (249 +/- 61.8 kPa). This difference was only statistically significant for the KTP laser group (P = 0.02) when compared with the scalpel group. CONCLUSIONS: Wounds created in the upper aerodigestive tract of rats by scalpels result in the least postoperative weight loss, tissue destruction, and decrease in tensile strength, whereas wounds created by the KTP laser demonstrated a significantly greater postoperative weight loss, depth of wounding, and decrease in tensile strength.     

Keratinocyte growth factor-2 accelerates wound healing in incisional wounds

BACKGROUND: Keratinocyte growth factor-2 (KGF-2) also described as fibroblast growth factor-10 (FGF-10) is a newly identified member of the fibroblast growth factor family. KGF-2 is 96% identical to the recently identified rat FGF-10 and specifically stimulates growth of normal human epidermal keratinocytes. The present study was undertaken to examine the effects of topically applied KGF-2 in an incisional wound healing model. KGF-2 treatment resulted in an improvement in incisional wound healing as characterized by an increase in breaking strength, collagen content, and epidermal thickness. METHODS: KGF-2 was topically applied to linear incisions made in the dorsal skin of Sprague-Dawley rats. Biomechanical testing was done using an Instron tensiometer for breaking and tensile strength determinations. Wound collagen content was determined using the Sircol collagen assay. Epidermal thickness measurements were conducted using Masson's trichrome-stained sections of the wound. RESULTS: A single topical application of KGF-2 at the time of wounding resulted in an increase in wound breaking and tensile strength at Day 5 after wounding. Breaking strength of KGF-2-treated wounds was significantly higher compared with the buffer control (1 microgram, 222.1 +/- 13.5 g, P = 0.0007; 4 microgram, 248.7 +/- 15.4 g, P = 0.0001; 10 microgram, 247.2 +/- 21.9 g, P = 0.001; buffer, 141.0 +/- 9.7 g). Epidermal thickness and wound collagen content were significantly increased following treatment with KGF-2. CONCLUSIONS: Based on our findings, KGF-2 is a potent stimulator of wound healing as demonstrated by increased mechanical strength accompanied by an increase in wound collagen content. KGF-2 could be an important cellular mediator responsible for the initiation and acceleration of wound healing and may enhance the healing of surgical wounds.     

Effect of photodynamic therapy on the healing of a rat skin flap and its implication for head and neck reconstructive surgery

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) may as adjuvant therapy by used to reduce tumor recurrence in the head and neck with surgery, given intraoperatively after resection. A concern with the use of intraoperative PDT is the possible effect on wound healing, especially on the healing of myocutaneous skin flaps, which are widely used to reconstruct defects following resections for head and neck cancer. STUDY DESIGN/ MATERIALS AND METHODS: A flap, based on the inferior epigastric artery, was prepared in thirty male Lewis rats. Group I did not receive any further treatment but the wound was left open for 20 minutes. Group II was injected with 5mg/kg Photofrin, 48 hours prior to the operation and also did not receive any further treatment. The wound bed and wound borders of group III were treated with 630nm light of different dosages, delivered by an argon dye laser. Animals in group IV received 5mg/kg Photofrin 48 hours prior to the operation and their wound beds were treated with the same light dosages as group III. After the treatment all flaps were replaced into the wound bed and the incisions were closed. Biopsies for histological analysis were taken at several time points; and on day 21, biopsies for wound tensile strength measurements were taken. RESULTS: The wound healing in group I, II, and III appeared normal and there were no differences seen between these groups. Also, the tensile strength did not differ significantly. The flaps of group IV showed serous effusion, epidermal necrosis, and weaker tensile strength (P = .04 and .02 for the light doses of 50 J/sq cm and 75 J/sq cm respectively) at a specific time point. CONCLUSION: The results of this study demonstrate that PDT given immediately before flap reconstruction will result in delayed wound healing. These results should be considered when contemplating the use of PDT as adjuvant intraoperative therapy for tumor surgery requiring flap reconstruction after ablative surgery.     

Late recurrence of a large post-infarction left ventricular pseudo-aneurysm. A case report

OBJECTIVE: To evaluate effects of treatment with a pulsed electromagnetic field (PEMF) on healing of open and sutured wounds, clinicopathologic variables, and CNS activity of dogs. ANIMALS: 12 adult female Beagles. PROCEDURE: Open and sutured wounds were created in the skin of the trunk of the dogs. Dogs were divided into 2 groups. One group received PEMF treatment and 1 group served as untreated (control) dogs. The PEMF-treated dogs received treatment twice a day starting the day before surgery and lasting through day 21 after surgery. Wounds were evaluated by use of tensiometry, planimetry, laser Doppler perfusion imaging, and histologic examination. Clinicopathologic variables and electroencephalographic tracings were also evaluated. RESULTS: Use of PEMF treatment resulted in significantly enhanced epithelialization of open wounds 10 and 15 days after surgery. Five days after surgery, wounds of control dogs had a negative value for wound contraction, whereas PEMF-treated wounds had a positive value. The PEMF treatment did not cause significant changes in short-term planimetric, perfusion, tensiometric, histologic, clinicopathologic, or electroencephalographic results. CONCLUSIONS: The PEMF treatment enhanced wound epithelialization in open cutaneous wounds and provided indications of early contraction without significant short-term changes in other variables.     

Laparoscopic versus open posterior adrenalectomy: comparison of acute-phase response and wound healing in the cushingoid porcine model

This prospective randomized study examined the acute-phase response and wound healing, comparing laparoscopic (LA) and open posterior (PA) adrenalectomy in a cushingoid porcine model. Repository corticotropin gel was given to 40 pigs for 21 days. Biochemical and tissue parameters of Cushing syndrome were confirmed. The pigs were randomized to undergo LA or PA. In addition to operating time and morbidity, the acute-phase response was compared by measuring the postoperative white blood cell count, fasting glucose, C-reactive protein, and nitrogen balance. Wound healing was assessed by (1) scored (1-4) gross appearance at 48 hours and 1 and 2 weeks; (2) histologic examination; and (3) tensile strength. There was no difference in operating time (mean +/- SD) (36 +/- 9 minutes open vs. 37 +/- 7 minutes laparoscopic), perioperative mortality, degree of leukocytosis, fasting glucose, or C-reactive protein (p > 0.05). Nitrogen balance, wound scores, and tensile strength at 24 hours and 1 week were more favorable in the LA group than in the PA group (p < 0.05). In the cushingoid porcine model, laparoscopic adrenalectomy was less catabolic and was associated with fewer wound complications than the open posterior adrenalectomy. These findings provide support for continued pursuit of laparoscopic methods for adrenalectomy in the clinical setting.     

BG-1 ovarian cell line: an alternative model for examining estrogen-dependent growth in vitro

Between 1.4.96 and 1.3.97 27 patients with acute infections of bone and soft tissues (n = 13), chronic osteomyelitis (n = 8), and chronic wounds (n = 6) were treated by using Instillation-Vacuum-Sealing. Polyvinylalcohol sponges with drainage tubes were used to cover the internal or external wound surfaces which resulted from surgical debridement. Having hermetically covered the wound with a transparent film dressing a vacuum source generated a partial vacuum in the sponge which was modified according to the type of wound between 20 and 80 kPa. Several times daily, the vacuum line was blocked and, in an alternating fashion, antiseptic or antibiotic solution instilled for 30 minutes. Then, the vacuum was reestablished and the fluids drained from the wound. Seven days later, intermittent drug instillation was stopped and there was either immediate or delayed wound closure by secondary suturing (n = 22), skin grafting (n = 3) or spontaneous epithelialization (n = 2). During a follow-up from the beginning of the instillation treatment of 4.2 (3-14) months there was one recurrency of infection in a patient with chronic osteomyelitis.     

Sequencing of double-stranded PCR products

Glutathione is a low molecular weight tripeptide that is a major intracellular antioxidant, modulates DNA synthesis, and may regulate signal transduction mechanisms. Our previous studies in rats suggested that intracellular stores of glutathione were sensitive to skin ischemia and, therefore, may regulate the early temporal course of wound healing. A 4-cm incision was placed on a rat's back and in vivo wound strength was measured over time. Animals were depleted of glutathione using L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of the enzyme gamma-glutamylcysteine synthetase. Some animals were treated in combination with allopurinol/BSO or with allopurinol alone. The data demonstrated at 4 days that BSO treatment produced a fourfold reduction in glutathione (3.51 +/- 1.78) over baseline (16.15 +/- 2.18) levels and twofold reduction (5.0 +/- 1.1) over untreated sham controls (11.1 +/- 2.3) (P < 0.05). Allopurinol provided no protection to glutathione levels. BSO treatment alone reduced wound burst strength compared to the other groups (P < 0.05). Allopurinol treatment enhanced wound strength over sham controls and BSO groups at 9 days after wounding (P < 0.05). Hydroxyproline content in wounds accumulated faster by Day 4 in the BSO-treatment groups compared to sham controls (P < 0.05), whereas the BSO-treatment groups had lower hydroxyproline levels measured at Day 6 (P < 0.05). These data provide the first evidence that wound healing is related to the temporal course of glutathione metabolism. The effect may not be related to oxidant stress since allopurinol provided enhanced wound burst strength without protecting wound glutathione levels.     

Elective stent implantation after optimal debulking for complex coronary lesions: acute and mid-term results

OBJECTIVE: To determine the vascular and collagen effects of supplemental basic fibroblast growth factor (bFGF) in irradiated porcine skin flaps. INTERVENTION: Animals were subjected to 2 fractions of 650 cGy orthovoltage radiation. Following this, the skin flaps were administered bFGF intracuticularly for 6 days before and after surgery. The animals were sacrificed 3 weeks after the start of bFGF administration. Tissues were analyzed for vascularity, collagen content, wound-breaking strength, and histopathological analysis. RESULTS: The bFGF-treated flaps showed a 62% increase in vascularity compared with controls (10.4%+/-2.4% vs 6.43%+/-2.27%; P<.05). The bFGF flaps had a significantly lower collagen concentration compared with control flaps when measured by hydroxyproline content (0.0619+/-0.0211 nm/microg vs 0.0784+/-0.0150 nm/microg). Wound-breaking strength was not significantly different, although the bFGF flaps had a trend toward lower breaking strength. Histologically, the bFGF-treated flaps showed increased cellularity, fibroblasts, and extracellular mucopolysaccharides compared with controls. CONCLUSIONS: This study provides evidence that supplemental bFGF can increase vascularity to skin flaps in previously irradiated porcine skin tissue. Histologically, radiation did not prevent the angiogenic effect of bFGF.     

Method for securing a subcuticular suture with minimal buried knot

Subcuticular, intradermal suturing with retained suture has been performed with a variety of techniques requiring bulky buried knots. This report outlines a new method for closing a skin wound under light to moderate tension with fewer problems of buried knot bulkiness and gapping of the wound ends. The suture method was developed in a porcine model and has been used in clinical suturing with 3-0, 4-0, and 5-0 suture material. Outcomes for 23 cases have been satisfactory with no dehiscences and no exposure of knot material. This technique provides the surgeon with an excellent way to approximate skin wounds with a retained sucuticular suture. A modified technique for small 3- to 10-mm wounds is also described.     

Wound healing after laser surgery

Compared with scalpel wounds, CO2 laser wounds show delays in inflammation, collagen production, reepithelialization, and tensile strength in the early stages of healing. Some of these delays are similar to those seen with electrocautery and burn wounds. Later stages compensate for these early deficiencies, because scalpel and laser wounds become more similar in epithelialization and wound strength over time. Healed CO2 laser wounds tend to have less scar contraction than scalpel wounds. Débridement of initial laser wound char, tissue cooling techniques during lasering, and pulsed modes of laser delivery all seem to result in more rapid, favorable healing. Similar wound healing trends have been seen with the CO2 laser in bone, with other lasers, and with laser vascular and neural anastomosis. Biostimulation with low-level laser energy is a complex subject of ongoing investigations.     

Use of octyl-2-cyanoacrylate for skin closure in facial plastic surgery

Octyl-2-cyanoacrylate is a long carbon chain cyanoacrylate derivative that is stronger and more pliable than its shorter chain derivatives. One hundred and eleven patients underwent elective surgical procedures by the same surgeon using either octyl-2-cyanoacrylate or sutures for skin closure at the University of Illinois at Chicago. Most patients underwent excision of benign skin lesions with a mean wound size of 112 mm3. Patients were randomized into either control (vertical mattress suture closure) or test groups (closure with octyl-2-cyanoacrylate). Surgical judgment was used to determine which wounds in each group required application of subcutaneous sutures to relieve tension and aid in skin edge eversion. Generally, full-thickness (through dermis) wounds larger than 1 cm3 required the use of subcutaneous sutures. The time required to close the epidermis with suture (mean, 3 minutes and 47 seconds) was about four times that of octyl-2-cyanoacrylate (mean, 55 seconds). Wounds were evaluated at 5 to 7 days for infection, wound dehiscence, or tissue reaction, and at 90 days using the modified Hollander wound evaluation scale. At 1 year, photographs of the wounds were evaluated by two facial plastic surgeons that graded the cosmetic outcome using a previously validated visual analog scale. There were no instances of wound dehiscence, hematoma, or infection in either group. Results of wound evaluation at 90 days determined by the modified Hollander scal revealed equivalent cosmetic results in both groups. Results of the visual analog scale ratings showed scores of 21.7 +/- 16.3 for the 49 patients treated with octyl-2-cyanoacrylate and 29.2 +/- 17.7 for the 51 control patients treated with sutures. The lower visual analog scale score represented a superior cosmetic outcome at 1 year with the octyl-2-cyanoacrylate as compared with sutures. This difference is statistically significant at p = 0.03. Additionally, patient satisfaction was very high in the group treated with octyl-2-cyanoacrylate.     

The minimal sequence needed to define a functional DNA terminator in Bacillus subtilis

BACKGROUND: We wished to determine whether transcutaneous oximetry or laser Doppler flowmetry (LDF) could identify patients at risk for wound failure after conservative, limb-sparing surgery for extremity sarcomas. METHODS: Studies were performed on postoperative days (PODs) 1, 4/5, 7, and 9. Measurements of transcutaneous oxygen pressure (tcPO2) were taken at breathing room air (BL) and 100% oxygen (rate tcPO2). LDF measurements were taken at multiple sites along the wound, and a perfusion index was calculated. RESULTS: Twenty-four patients were studied. Four (17%) had nonhealing wounds. There was no difference in tcPO2 (BL) values between healed and nonhealing wounds. Measurement of rate tcPO2 on POD 1 was significantly lower in the nonhealing wounds than in those with normal healing (28.5 +/- 12.1 mm Hg vs 14.3 +/- 16.2 mm Hg, mean +/- SD, p = 0.03). Rate tcPO2 values increased significantly in healing wounds from POD 1 to PODs 7 and 9 (p = 0.006, p = 0.009). This increase was absent in nonhealing wounds. A clear separation was noted in rate tcPO2 values between groups, with a minimum rate tcPO2 value recorded in a healed wound of 9 mm Hg/min, compared with the maximum value in a nonhealing wound of 7 mm Hg/min. The LDF perfusion index failed to predict wound healing at any of the measured time points. CONCLUSIONS: This study showed that measurement of tcPO2 during oxygen inhalation can accurately predict wound healing in patients after excision of an extremity sarcoma.     

Reduction of skin flap necrosis by transdermal application of buflomedil bound to liposomes

The influence of the vasoactive drug buflomedil hydrochloride bound to liposomes (2 mg/ml) was investigated in an arterial pattern skin flap model using the ear of hairless mice. For flap creation, the ear is cut at four-fifths of its base, which leaves the anterior artery as the only feeding vessel of the flap. Liposomes were locally applied daily for 30 minutes up to 5 days after flap creation. Microvascular perfusion in the proximal, central, and distal parts of the flap was measured by laser Doppler flowmetry. The border between perfused and nonperfused tissue was visualized by intravital fluorescence microscopy using fluorescein isothiocyanate (FITC)-labeled dextran (Mr 150,000) for contrast enhancement of microvessels. The area of nonperfused tissue was assessed by digital planimetry. Five days after flap creation the nonperfused area amounted to 23.8 +/- 3.1 percent of total flap surface in treated ears compared with 46.1 +/- 5.6 percent in untreated ears (p < 0.05) of the contralateral side. Additional preoperative treatment for 5 days did not further reduce the area of nonperfused tissue (treated ears, 23.0 +/- 1.3 percent; control ears, 44.6 +/- 5.1 percent). Microvascular perfusion was higher in the postoperatively treated ears in all parts of the flap from day 1 after flap creation until termination of the experiment. Five days after flap creation, perfusion as measured by laser Doppler flowmetry was reduced to 46.0 +/- 10.8 percent in the distal part in control ears compared with 91.9 +/- 8.3 percent (p < 0.05) in treated animals. Additional preoperative treatment for 5 days did not result in further improvement. It is concluded that local application of the vasoactive drug buflomedil docked to liposomes could be of therapeutic use in the treatment of ischemic tissue, including skin flaps.     

Influence of biosynthetic human growth hormone on the biomechanical strength development in skin incisional wounds of diabetic rats

The influence of biosynthetic human growth hormone (b-hGH) on the mechanical strength development of skin incisional wounds in diabetic rats has been investigated after 4, 7 and 21 days of healing. Diabetes caused decreased mechanical strength of the wounds. After 21 days of healing, the diabetic animals treated with b-hGH from 7 days before wound infliction had an increased maximum load (14%) compared with the untreated diabetic animals. After 4 and 7 days of healing, no differences in the biomechanical strength of diabetic wounds with and without b-hGH treatment were found. The diabetic animals receiving b-hGH showed a significant increase in body weight compared with the untreated diabetic animals. In the diabetic animals, the blood glucose concentration was increased by treatment with b-hGH. In conclusion, treatment with b-hGH from 7 days before operation can counteract the reduced mechanical strength of skin wounds in diabetic rats on day 21.     

2-Iminothiazolidine-4-carboxylic acid produces hippocampal CA1 lesions independent of seizure excitation and glutamate receptor activation

Impaired wound healing is a common complication of diabetes mellitus. The underlying pathophysiology of diabetes-impaired healing is poorly understood. In the present study we have compared cell proliferation rates, apoptosis (programmed cell death), the myofibroblast marker alpha-smooth muscle actin and procollagen I mRNA expression, between diabetic and control mice. Full-thickness skin wounds were made in non-obese diabetic (NOD) mice and C57B6 controls. NOD mice showed a marked retardation of wound healing at both 7 and 14 days after wounding. Comparison of cell proliferation rates 7 days after wounding, using 5-bromo-2'-deoxy-Uridine incorporation, showed higher rates of cell proliferation in controls (88.1 +/- 12.8) than in NOD wounds (52.1 +/- 9.9, p < 0.02, n = 4). Immunohistochemical detection of alpha-smooth muscle actin, showed a later onset in diabetic wounds, suggesting that wound contraction may be delayed in the diabetic animals. In situ hybridisation for alpha 1 (I) procollagen mRNA expression, showed reduced procollagen I expression in the diabetic wounds when compared with controls. Lastly, there appeared to be higher levels of apoptosis in diabetic wounds, shown by the terminal transferase mediated UTP nick end-labelling technique. Apoptotic cells were rare in control wounds confirming previous studies, which showed that apoptosis occurs late in normal wound healing as the wound matures into scar tissue. In conclusion, we hypothesize that reduced cell proliferation, retarded onset of the myofibroblast phenotype, reduced procollagen I mRNA expression and aberrant control of apoptotic cell death may contribute to impaired wound healing seen in this diabetic model.