Leukocyte behavior in a free-flap model following chemotherapy and application of granulocyte colony-stimulating factor (GCSF).

Free-flap reconstruction following tumor resection and chemotherapy is used increasingly in sarcoma patients. Granulocyte colony-stimulating factor (GCSF) is used to stimulate polymorphnuclear leukocytes (PMNs). In this study we used a free-flap model to investigate PMN behavior after chemotherapy and GCSF stimulation. Eighteen Lewis rats were divided into three groups: (1) chemotherapy + vehicle; (2) chemotherapy + GCSF; and (3) control. Group 1 received vinblastine; group 2 received vinblastine plus 300 microg rhGCSF. Blood was drawn for total white cell and PMN counts for 9 days. Free-flap surgery was simulated by isolating the cremaster muscle on its pedicle and anastomosing the artery. Leukocyte-endothelium interaction was assessed by observation of leukocytes rolling and sticking. Leukocyte sequestration was measured by counting leukocytes in the lungs and the abdomen. We found that leukocyte rolling and sticking were significantly increased, while sequestration was decreased in the chemotherapy + GCSF group. We conclude that leukocytes-endothelium interaction after chemotherapy and GCSF administration is increased in the microcirculation. This augments the risk of microvascular compromise and subsequent flap failure, as capillary flow may be altered.

Microcirculatory studies of frostbite injury.

Frostbite represents a spectrum of injury ranging from irreversible cellular destruction to reversible changes seen after rewarming. These changes include increases in tissue edema, circulatory stasis, and progressive thrombosis leading to further tissue necrosis. For this reason, it is often difficult at the time of surgical debridement to determine the extent of frostbite injury. This delayed tissue injury is similar to that seen in muscle during ischemia/reperfusion injury. Muscle that initially appears viable on reperfusion may subsequently necrose due to collapse of the microcirculation. Adherent neutrophils have been specifically cited as important components in ischemia/reperfusion injury and have also been suggested to play a role in frostbite injury. We have used an intravital microscopic muscle preparation to study microcirculatory changes carefully in frostbite injury during rewarming. The right gracilis muscle of male Wistar rats is dissected free from its primary vascular pedicle and the rat is positioned on a specially constructed microsurgical stage. Temperature changes of the muscle are recorded. The prepared axial pattern flap is transilluminated with a microscope and projected on a video screen, allowing measurement of arteriolar diameters and changes in the numbers of stuck and rolling neutrophils before frostbite, during rewarming, and for several hours later. Cold silicone oil is used to freeze the muscle to -5+/-2 degrees C in 2 to 3 minutes and to hold this temperature for 5 minutes. The muscle is rewarmed with 42 degrees C normal saline placed directly on the muscle surface. Baseline vessel diameter and leukocyte counts in 100-mm segments of the microvasculature are recorded as well as at 5, 15, and 30 minutes, and at 1, 2, and 3 hours postrewarming of frozen muscle. Observations from our initial 11 animals show that reperfusion of the muscle following freezing is varied temporally and spatially, with circulation to most vascular segments restored 5 to 10 minutes after rewarming. In 9 of 11 animals we observed the shedding of "white clots" in small arterioles and venules occurring as soon as 5 minutes after thawing. In some instances shedding continued for as long as 1 hour after rewarming. Microvascular hemorrhage was widespread 1 hour following the thaw, but there was no significant increase in neutrophil adherence observed until 3 hours following rewarming. The exact nature of the vascular injury and the composition of the "white clots" are now being determined from ultrastructural studies. Blood flow in microcirculation stops during freezing, but small-vessel perfusion returns immediately on thawing. This suggests that the vascular architecture is maintained during the freezing and thawing. Unlike ischemia/reperfusion injury, neutrophil adhesion plays a smaller role in the early response to frostbite injury. The early microcirculatory observations seen after rewarming suggest progressive and severe perturbations in platelet function and fibrin formation that are significantly different from ischemia/reperfusion injury.

Elevated compartmental pressures after closure of a forearm burn wound with a skin-stretching device.

A case of successful delayed primary closure of an upper extremity electrical blow-out injury is described using an alternative technique. The Sure-Closure skin-stretching device was used for permanent wound closure following serial debridement to protect the radial artery which was exposed over a distance of 21 cm. This method increases the options possible to achieve wound closure. However, the potential risks of this method include potentially high compartment pressures over a prolonged time in the postoperative period which requires close monitoring of limb perfusion.

[Diagnosis and therapy of calcifying intramuscular hemangiomas of the lower extremity]. / Diagnose und Therapie kalzifizierender intramuskulärer Hämangiome der unteren Extremität.

During a 6 year interval from 1990 to 1996 13 patients suffering from calcifying cavernous hemangioma of the lower extremity were treated by surgical resection of the tumor and were followed-up postoperatively for remaining functional loss and recurrence rate. The resection of the medial head of the gastrocnemius muscle was performed seven times, the resection of the lateral head was done in 5 patients. In one patient the soleus muscle was partially resected. Simultaneous lengthening of the Achilles tendon was done in 11 patients for correction of foot drop deformity. The histological examination revealed three cavernous hemangiomas, one arterio-venous angioma racemosum and nine mixed capillary-cavernous hemangiomas. The patients were able to walk at 5.3 weeks following surgery. During the 29 months follow-up period there was no recurrence of symptoms neither of the hemangioma.

[Thrombosis and tissue protection in microvascular surgery--an overview]. / Thrombose- und Gewebeschutz in der Mikrovaskularchirurgie--Eine Ubersicht.

Although microvascular surgery has become a safer procedure in recent years, failure still occurs. The main cause of failure is thrombosis of the anastomosed vessels. Thrombosis involves the vascular wall, platelets and the coagulation system. Sometimes the transferred tissue dies with the anastomoses open. This is caused by an insufficient perfusion at the microcirculatory level, e.g. a reduction of capillary inflow by arteriolar vasoconstriction. Tissue damage also occurs after ischemia and reperfusion. Oxygen free radicals and activated leukocytes are responsible for this phenomenon. Thrombosis can be reduced by antiplatelet and anticoagulant drugs, substances increasing fibrinolysis and other agents. In the clinical situation, aspirin, heparin and dextrane have proven reliable. The microcirculation can be protected by aspirin. Reperfusion injury is affected with superoxide-dismutase, allopurinol and perfusion solutions. Future developments in this field will include locally applied antithrombotic agents and substances acting more specifically.

Spontaneous esophageal perforation in an acute burn patient.

Spontaneous perforation of the esophagus is an uncommon and catastrophic event accompanied by extremely high morbidity and mortality. In a burn patient, diagnosis may be delayed because of painful burns that may mask the underlying problem. Diagnosis is dependent on a high index of suspicion and by inclusion of this entity in the differential diagnosis of chest pain. The authors report on a 45-year-old male who developed a spontaneous perforation of the esophagus while hospitalized for treatment of an 11% total body surface area burn. Diagnosis and initiation of appropriate treatment resulted in salvage of this patient. The pathophysiology of this disease and a review of the literature are presented.

[Lymphocyte subpopulations in spleen and blood after early wound debridement and acute/chronic treatment with hyperbaric oxygen]. / Lymphozyten-Subpopulationen in Milz und Blut nach frühzeitigem Wunddébridement und akuter/chronischer Behandlung mit hyperbarem Sauerstoff.

Thermal burns as well as hyperbaric oxygen (HBO) may cause immuno-suppression. This is one of the reasons why there is some controversy in the literature regarding adjuvant HBO treatment for thermal burn patient, despite the fact that HBO is known to decrease edema formation and possibly inhibits the progression from second to third degree burns. In this study, lymphocyte subpopulations were labelled with monoclonal antibodies W3/25 for helper cells, and OX-8 for cytotoxic/suppressor cells, to determine changes following early burn wound excision and acute or chronic HBO treatment in a 10% full-thickness burn model in rats. Lymphocyte subpopulations were extracted from blood and spleen on day 1, 8, and 15 following burn and/or treatment. W3/25 cells did not show any significant changes in blood or spleen over time. Significantly lower OX-8 cell counts were found in the group with burn + excision + chronic HBO treatment on day 8 and 15. Acute or chronic HBO treatment alone did not produce evidence of immuno-suppression.

Hyperbaric oxygen and cyclosporine as a combined treatment regimen to prevent skin allograft rejection in immunohistoincompatible mice.

Several previous studies reported various immunosuppressive effects of hyperbaric oxygen on nonspecific and specific cell-mediated reactions. A highly immunogenic skin allograft mouse model was used to evaluate the clinical relevance of the previously described immunosuppressive effects of hyperbaric oxygen. A 1.5 x 2.0-cm full-thickness skin allograft was cross-grafted between paired immunohistoincompatible mouse strains (N = 40, C57BL/6 and BALB/c female mice) that were randomly assigned to four groups receiving (1) no treatment (controls), (2) cyclosporine 1 mg per kilogram intraperitoneally daily, (3) cyclosporine plus a low-dose hyperbaric oxygen treatment (two treatments per day, once a week), and (4) cyclosporine plus a high-dose hyperbaric oxygen treatment (two treatments per day, three times a week) following surgery (N = 32). Allograft samples were taken from each group at day 9 after cross-grafting (N = 8). Skin allograft rejection was significantly delayed in all treatment groups compared to controls. No difference was found between animals who received cyclosporine only and the combined treatment regimen including low-dose hyperbaric oxygen. High-dose hyperbaric oxygen treatment in combination with cyclosporine substantially prolonged skin allograft survival compared to other treatments. These findings were histologically confirmed. We conclude that hyperbaric oxygen treatment as an adjunct to standard immunosuppressive therapy may only be advantageous if frequently applied.

Treatment of a severe alkali burn.

The case history of a 20-year-old male patient who sustained an 85 per cent total body surface area alkali burn to his skin, after falling into a caustic lime pit, is reported. Considerable problems regarding the correct estimate of burn wound depth, predominant location of the deepest burn on the posterior half of the body, appropriate wound coverage, and lack of sufficient skin graft donor sites required a complex treatment plan. Excisions to fascia and intradermal debridement were required to achieve an appropriate bed for wound closure. Five per cent mafenide acetate solution (Sulfamylon) was applied to prevent burn wound sepsis. Human allografts and Biobrane were used extensively to achieve temporary wound closure, to provide mechanical protection of freshly autografted wounds, and to prevent desiccation following application of cultured epidermal autografts on to debrided wounds and split thickness skin grafted donor sites. The case illustrates a number of problems associated with the evaluation and treatment of patients suffering severe alkali burns, and demonstrates the implementation of both established and evolving technologies in the management of these injuries.

[Indications for arterialization of tissue]. / Indikationen für die Arterialisation von Gewebe.

Data from 69 arterialized venous flaps and transplants were reviewed and showed on overall complication rate of 18.6%. Possible hemodynamic mechanisms include, among others, the opening of macro- and microvenous interconnecting pathways with in the perivenous areolar tissue and pressure-induced insufficiency of venouf valves. The use of arterialized venous flaps increases the plastic surgeon's armamentarium if standard local or distant flap procedures are not possible, and the use of a vein to provide arterial inflow into an amputated body part presents a suitable alternative if arteries are not available and venous congestion is controlled.

A model for recording the microcirculatory changes associated with standardized electrical injury of skeletal muscle.

The rate of major limb amputation following high voltage electrical injury remains high despite a decrease in mortality rate. Several theories about the pathophysiology of electrical injury have been discussed in the literature and different clinical regimens have been attempted to decrease the high amputation rate. However, to date, the overall tissue response after electrical injury remains incompletely understood with nothing new to offer these unfortunate patients. We have developed a rat gracilis muscle intravital microscopy preparation in order to better understand the mechanisms of this injury. A standardized 40-V stimulation of 10-sec duration was applied to the anterior belly of the gracilis muscle which translated into a current load of 30 mA. The current density was 750 mA/cm2. Sequential intravital assessment of microcirculatory changes before injury, as well as 5, 15, 30, 60, 120, 180 and 240 min after injury was performed. Consistent findings included initial cessation of blood flow in many capillary beds, focal flow reversal, venous and arterial vascular spasm. Restitution of microvascular flow varied from several minutes to 1 hr and was preceded by vasodilation at 5-15 min following the injury (+16.9 microns from baseline at 15 min). Starting at 30 min progressive vasoconstriction was noted (-0.8 micron from baseline at 30 min, -31.3 microns from baseline at 4 hr). High resolution observation of neutrophil behavior showed an increase in the number of these cells adherent to venular endothelium in areas exhibiting circulatory disturbances (+11.4 cells at 5 min, +15 cells at 4 hr). The standardization of this model allows a quantitative method of evaluating the microcirculatory changes associated with electrical injury and of studying ways to prevent tissue damage. The microcirculatory changes induced by electrical injury were similar to those reported in ischemia-reperfusion injury of skeletal muscle.

Skin allograft rejection and hyperbaric oxygen treatment in immune-histoincompatible mice.

The effect of hyperbaric oxygen (HBO) as an immunosuppressive agent was evaluated by using a highly immunogenic skin allograft mouse model. Immune-histoincompatible female C57BL/6 and BALB/c mice (N = 30) were randomly assigned to three groups receiving no treatment (control group), low dose HBO treatment (two treatments once a week), and intermediate HBO treatment (two treatments 3 times/wk) 1 wk before and 2 wk after transplantation of a 1.5 x 2 cm full thickness skin allograft from the back. Rejection was observed a Day 7 and was completed 14 days after surgery in controls. Low dose and intermediate HBO treatment delayed skin allograft rejection, which was histologically confirmed.

Electrical injuries--morbidity, outcome and treatment rationale.

Electrical injuries are unique with respect to low mortality rates, but very high rates of short- and long-term morbidity, and overall outcome. Controversy still exists regarding the advantages of one-stage debridement versus early serial debridement of necrotic tissue. The purpose of this study was a retrospective evaluation of treatment, morbidity and outcome in a group of patients with electrical injuries. Over a 13-year period 1992 patients were admitted with acute burns to our burn centre. Electrical injuries occurred in 129 (6.5 per cent) of these patients. There were 38 high-tension injuries and 91 low-tension injuries. The average age was 33.7 years (5 months to 63 years), with burn wounds ranging from 1 to 57 per cent total body surface area (mean 9.5 per cent). Ninety-four (72.9 per cent) of these injuries were work related, and most occurred in males (85 per cent). A total of 323 surgical procedures were performed on those 129 patients. An average of 0.48, surgical debridements per patient was necessary in the low-tension injury group and only three partial finger or toe amputations were necessary. In the high-tension group, 27 major limb amputations were performed after 2.3 debridements per patient, resulting in an overall major limb amputation rate of 35 per cent. The average length of stay was 22 days, and the cost of hospitalization ranged from $900 to $120 000 (mean !4,901). Significant long-term neurological deficits persisted in 73 per cent of patients at long-term follow-up (mean 4.5 years). Only 5.3 per cent of patients after high-voltage electrical injury were able to return to their premorbid job.

[The value of technetium scintigraphy for early diagnosis and therapy of severe frostbite]. / Die Bedeutung der Technetium-Szintigraphie für die frühzeitige Diagnose und Therapie schwerer Erfrierungen.

Frostbites often present with a discrepancy between skin lesions and damage to deeper structures. 14 patients with the diagnosis of severe frostbite and/or hypothermia had been treated between 1990 and 1993. In addition to our standard approach including history, physical exam, and Doppler/Laser-Doppler studies, we performed technecium 99 scintigraphies in seven patients at three to five days after injury. In six patients (86%), there was an excellent correlation between scintigraphic and intraoperative findings. We conclude that early diagnosis and treatment of avital tissue reduces length of hospital stay and allows for maximum amputation stump length preservation.

Overwhelming postsplenectomy sepsis in a patient with burns: a case report and a rational approach to treatment.

Overwhelming postsplenectomy sepsis is a dreaded sequel of splenectomy. The rate of overwhelming sepsis in children after splenectomy for trauma is reported to be 10 to 30 times that of the general population. Episodes of pneumonia, septicemia, and meningitis in adults after a splenectomy are 166 times more common than in the general population. The care of a patient with burns and asplenia presents many unique management challenges to the burn physician. Awareness of the development of overwhelming postsplenectomy sepsis and its most common infecting organisms is crucial. The specific immunologic deficiencies of reduced immunoglobulin production and cell-mediated immunity that exist in patients after a splenectomy may be compounded by burn injury. Specific treatment recommendations for patients with burns and asplenia are lacking. We report a fatal case of overwhelming sepsis in a patient with asplenia and with an 8% total body surface area partial-thickness burn, and we review the pathogenesis of overwhelming postsplenectomy sepsis. We focus on treatment recommendations regarding the use of prophylactic antimicrobials, intravenous immunoglobulin replacement therapy, and pneumococcal polyvalent vaccine to standardize the care of the patient with burns and asplenia and reduce infectious morbidity and deaths.

Toxic epidermal necrolysis: a review and report of the successful use of Biobrane for early wound coverage.

Toxic epidermal necrolysis (TEN), is an exfoliative dermatological disorder of unknown cause. A patient with TEN loses epidermis in sheet-like fashion, leaving extensive areas of denuded dermis that must be treated like a large, superficial, partial-thickness burn wound. Methods of coverage described in the English literature over the last decade include the use of several dressings such as fresh-frozen or cryopreserved cadaver allograft, porcine xenograft, and amnionic membrane. Successful use of the biosynthetic dressing, Biobrane, has been described after burn injuries and Stevens-Johnson syndrome; however, its use in TENS has not. We present three patients with TEN treated successfully in our burn center over the past 12 months using Biobrane. The patients were men aged 20, 58, and 77 years, with 58% to 95% total body surface area slough. Diagnosis was confirmed by skin biopsy on admission, and drug ingestion was implicated in each instance. Each patient was thoroughly debrided in the operating room shortly after admission, and denuded areas were covered with Biobrane within 24 to 48 hours of admission. Biobrane demonstrated greater than 90% adherence by 48 hours, and no wound sepsis occurred. Each patient demonstrated epithelialization within 9 days. Patients were ambulatory at 72 hours. Corticosteroids and prophylactic antibiotics were avoided. Enteral nutritional support and aggressive septic surveillance was routine. Hospital stay was between 13 and 30 days without mortality. Early use of Biobrane in patients with TEN appears to provide a reasonable means of wound coverage.

[Biological and molecular biology aspects of burn therapy]. / Biologische und molekularbiologische Aspekte der Verbrennungstherapie.

Early wound closure, permanent skin replacement and management of postburn deformities are still unsolved problems in the treatment of burns. However, recent developments in biology and molecular biology provide new possibilities for improved therapy. This includes the enhancement of burn wound healing by growth factors and growth hormone, modulation of immunogenicity of skin allografts by gene transfer, cytokine treatment of burn sepsis and the use of cell membrane stabilizers in electrical injuries.

Soft-tissue calcifications: differential diagnosis and therapeutic approaches.

Calcification of soft tissue may be an unspecific local response or present as only a symptom of a complex underlying disease. Patient approach and treatment vary greatly depending on the cause of soft-tissue calcifications. The review of literature reveals multiple causes but also confusing nomenclature for similar clinical entities. Dystrophic and metastatic soft-tissue calcifications are discerned, but there is also contribution of both types of soft-tissue calcification to some syndromes. Six previously unpublished cases of soft-tissue calcification including Thibièrge-Weissenbach syndrome, scleroderma (progressive systemic sclerosis), calcifying cavernous hemangioma (2 patients), and heterotopic calcifications after burn injury (2 patients) are presented to discuss the differential diagnosis. The correct diagnosis is crucial for successful treatment. Resections of the lateral heads of the gastrocnemius muscles in 2 patients resulted in cure of the problem. The patient suffering from Thibièrge-Weissenbach syndrome had no recurrence during a 30-month postoperative follow-up period. Surgical treatment of scleroderma or soft-tissue calcification after burn injury is aimed toward relief of symptoms. A proposal for patient assessment and indications for surgical correction with regard to soft-tissue calcifications is presented and discussed.

Use of glycerolized human allografts as temporary (and permanent) cover in adults and children.

Multiple efforts to achieve immediate and complete burn wound closure following early debridement have been attempted to prevent septic complications, and to decrease the morbidity and mortality associated with major burns. The BG University Hospital Bergmannsheil Bochum (BGUBB) Burn Centre admitted 157 patients with deep partial thickness and full thickness skin burns during 1991 and 1992. Twenty-eight of these patients (18 per cent) were treated with glycerolized human allografts. A total of 57 allograft transplantations were performed on these 28 patients. Our indications for the use of glycerolized human allografts, as well as our results, are presented and discussed.