Effect of free-radical scavengers and hyperbaric oxygen on random-pattern skin flaps.

OBJECTIVE: To determine whether treatment with the combination of hyperbaric oxygen and free-radical scavengers or inhibitors would result in increased skin-flap survival. DESIGN: An animal model with male Sprague-Dawley rats was used. The flap was a cranial-based dorsal 3 x 12-cm random-pattern skin flap that included the panniculus carnosus. Rats were randomly assigned to one of 10 treatment groups. INTERVENTIONS: The radical scavengers superoxide dismutase, catalase, and alpha-tocopherol acetate and the inhibitor allopurinol were used to combat or scavenge radicals. Oxygen (100%) treatments were for 90 minutes at 2.5 atm absolute daily. MAIN OUTCOME MEASURES: At 7 days, the flaps were examined for survival by fluorescein injection. Lipid peroxidation as a measure of tissue damage was measured by thiobarbituric acid-malondialdehyde analysis. RESULTS: The combination of treatments resulted in significantly increased flap survival compared with untreated controls (P < .05) except in the group treated with allopurinol and hyperbaric oxygen. Lipid peroxidation was inhibited by the superoxide dismutase plus catalase and the alpha-tocopherol treatments but not by treatment with allopurinol. CONCLUSION: Moderate doses of radical scavengers or antioxidants coupled with a conservative hyperoxic exposure regimen can result in the increased survival of random-pattern skin flaps.

Effect of radical scavengers and hyperbaric oxygen on smoke-induced pulmonary edema.

Respiratory complications, especially pulmonary edema, account for over 50% of mortalities in inhalation injuries. This study was conducted to determine the effect of free radical scavengers and hyperbaric oxygen (HBO) in vivo on reducing pulmonary edema. Adult New Zealand rabbits were allowed to breath cooled, cotton smoke until a significant inhalation lung injury was produced. Five percent of body weight lactated Ringer's solution was then administered i.v. over 2 h. The following free radical scavengers were given as bolus infusions at the beginning of fluids resuscitation: superoxide dismutase, catalase, butylated hydroxytoluene/piperonyl butoxide, and mannitol. At the completion of fluid administration, half of the subjects were given HBO treatment. Pulmonary edema was then measured as extravascular lung water and wet/dry lung weight. Results indicate that free radical scavengers or HBO reduce pulmonary edema. Free radical scavengers in conjunction with HBO showed no significant improvement over HBO or free radical scavengers alone.

Measurement of free radicals from smoke inhalation and oxygen exposure by spin trapping and ESR spectroscopy.

Research in smoke inhalation has established that free radicals are produced from gases released during combustion and these species impair lung function. Using spin traps and their adducts in an animal model free radicals were measured. Various hyperbaric oxygen regimens were tested in an attempt to attenuate pulmonary damage caused by free radical reactions. Our data demonstrated that persistent oxygen- and carbon-centered free radicals are detectable in intravascular fluids after smoke inhalation. The smoke inhalation model showed however, clearing of spin trap adducts one hour after smoke exposure. Other researchers have found that when 100% oxygen is given at 1 atmosphere absolute (ATA) for 1 h, free radicals were not detectable. However, oxygen given at 2.5 ATA does produce detectable free radicals. With continued exposure at this pressure, the levels of free radicals increase for up to 60 min. This study suggests that the level of free radical induced oxygen toxicity may be a function of oxygen pressure and duration of oxygen exposure.

Effects of ibuprofen on pulmonary oedema in an animal smoke inhalation model.

The ability of ibuprofen to lower extravascular lung water significantly was examined in an animal smoke inhalation model. Adult New Zealand White rabbits weighing 3-5 kg were anaesthetized and intubated. They were then allowed to breathe cooled cotton smoke until the carboxyhaemoglobin (COHb) reached a level of 60 per cent or higher. Each ibuprofen-treated animal received a dose of 50 mg/kg either intraperitoneally or intravenously. Ibuprofen was administered to animals that received smoke inhalation alone and those that received smoke inhalation combined with a 10 per cent BSA partial skin thickness thermal injury. Control groups were established for both of the above-mentioned groups. Peak carboxyhaemoglobin levels as well as CO half-lives were not significantly different between ibuprofen-treated groups and the controls. Ibuprofen treatment resulted in significantly (P less than 0.05) decreased lung water in both smoke, and smoke plus thermal injury groups as compared to controls. These results suggest that ibuprofen promotes the reduction of early-onset lung water resulting from smoke inhalation injury alone or from smoke inhalation injury plus a thermal injury.

Effect of high-dose cimetidine on pulmonary extravascular water after acute smoke inhalation injury.

An animal model utilizing gamma imaging was used to examine pulmonary edema of an inhalation injury model. Tests were conducted using radiolabeled tracers and a dual indicator dilution technique as well as gravimetric analysis of excised lungs to determine extravascular water formation. The effect of cimetidine (Tagamet, an H2 receptor antagonist) was investigated as a potential agent for reduction of pulmonary edema following inhalation injury. Control groups included no treatment; smoke only; fluids only; and smoke and fluids. These were compared with identical groups given the same treatments but with the addition of cimetidine (100-150 mg/kg body weight intravenously). Fluids administered were 5% body weight intravenous infusions of lactated Ringer's solution over two hours. Results show that pulmonary edema was evidenced in animals given an inhalation injury, and was markedly worsened by fluid resuscitation. Treatment with cimetidine at high doses, either before or after inhalation injury, did not protect the animals from formation of pulmonary edema.

Early detection of extravascular lung water in an inhalation injury animal model.

A rabbit inhalation injury model using a dual tracer radioactive isotope technique (Rowland et al., 1986), has been utilized with small- and medium-sized molecular weight tracers. There is oedema formation at 2 h after smoke inhalation or fluid resuscitation and especially with the combination of inhalation injury and fluid resuscitation [corrected]. This oedema appears to have decreased by 24 h post-injury. There does not appear to be any difference between the small- and medium-sized tracers in the transit times of tracer in the lung vascular compartment. The increases in extravascular water volume have been confirmed by gravimetric analyses of the lungs. Thus the pulmonary oedema in the rabbit animal model is detectable within 2 h post-injury, with a return towards normal values some time within 24 h if fluid challenged for short periods. Fluid resuscitation exacerbates the amount of oedema that developed. The onset of pulmonary oedema may therefore be earlier than previously seen clinically, and fluid resuscitation modifications may be of benefit in smoke inhalation injury.

Frostbite and bone scanning: the use of 99m-labeled phosphates in demarcating the line of viability in frostbite victims.

Early diagnosis of the extent of bone and soft tissue damage is a very important step in treating a frostbite victim. The diagnostic use of Tc-99m-phosphates in assessing the viability of soft tissue and bone in frostbite was evaluated in the early post-thaw period. Four patients were treated with a combination of warm baths, rehydration, vasodilators, epidural block, fasciotomy, and debridement. Six scans were done to stage involvement. In three of the four cases, final involvement could be determined as early as the third day. When a specific level of soft tissue or bone uptake was determined, future scanning showed either improvement, or no change in three of the four patients. In our experience, Tc-99m-phosphate scans represent an improvement over other diagnostic tests for viability of tissues.

Effects of antioxidants and hyperbaric oxygen in ameliorating experimental doxorubicin skin toxicity in the rat.

Doxorubicin, an antineoplastic drug, can cause severe ulceration if extravasated when iv injected. In this study, the effects of hyperbaric oxygenation (HBO) and the antioxidants butylated hydroxytoluene (BHT) and beta-carotene were tested on such ulcers using female Sprague-Dawley rats. It was found that HBO and vitamin A did not greatly ameliorate the ulcers produced by doxorubicin, but BHT prefed for 1 week before doxorubicin was injected was able to significantly reduce lesion size (P less than 0.05). Doxorubicin with HBO was a lethal combination, with an 87% mortality among the animals by the fourth week after injection. This was probably due to doxorubicin and HBO both promoting the formation of free radicals which are highly destructive to cells. BHT, when prefed (and to a lesser extent, beta-carotene), demonstrated a protective effect by lowering the death rate (P less than 0.05), probably due to their ability to scavenge free radicals. This experiment also tested more conventionally recommended treatments such as sodium bicarbonate (NaHCO3), hydrocortisone, and ice. NaHCO3 and hydrocortisone decreased lesion size although only at a significance of P less than 0.10. Ice did not aid in the healing of the doxorubicin-induced ulcers and even proved deleterious. Multiple injections of hydrocortisone or NaHCO3 appeared to deepen ulceration. Of all the treatments tested, free radical scavengers appear to most significantly reduce skin toxicity of doxorubicin.

Smoke inhalation model for lung permeability studies.

The purpose of this project was the development of a small animal model and the use of external gamma imaging for the study of acute post-inhalation permeability changes. New Zealand white rabbits were anesthetized with ketamine and acepromazine IM, intubated, and a catheter placed in an ear artery. Smoke was produced by burning absorbent cotton in a combustion chamber supplied with 10 liters/min of air. Smoke was delivered to a holding chamber, allowed to cool to room temperature, and immediately delivered to the animals via endotracheal tube. Animals were allowed to inhale smoke for 3 sessions of 2 to 3 minutes. Blood samples were collected for the measurement of PO2, PCO2, and COHb. Lungs were removed at 3 to 4 days postinjury and subjected to microscopic histologic analysis. The results of six animal experiments showed a significant inhalation injury. The mean COHb level was 48% (range, 36%-58%). The change in the pre- and post-injury PO2 and PCO2 values were not significant (mean PO2, 66 mm Hg; mean PCO2, 32 mm Hg). Histologic evaluation of the lungs of three animals at 24 hrs postinjury revealed extensive loss of tracheal epithelium extended to many terminal bronchi. Inflammation of surrounding tissue, including edema and increased migration of polymorphonuclear cells, was also present. Analysis of tissue obtained at 10 to 14 days showed reparative reepithelialization of trachea and major bronchi but acute inflammation and loss of intralobar bronchi. Inflammatory exudate extended to adjacent alveoli. In conjunction with the above model we have developed a method for the noninvasive measurement of lung permeability changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic value of fine needle aspiration biopsy in neoplasms of the head and neck.

In this paper, the cytologic findings of 90 aspirates obtained by the fine needle aspiration technique from head and neck masses are compared with the histology of the permanent section. The overall concurrence rate between cytologic and histologic findings for benign and malignant tumors is 80%. There is a 6.6% false negative rate. There are no false positive results. Fine needle aspiration biopsy is found to be safe, complication free, and most helpful in treatment planning.

Induction chemotherapy in advanced squamous head and neck carcinoma with high-dose cis-platinum and bleomycin infusion.

Forty patients with advanced head and neck cancer were treated with combined Cis-platinum-Bleomycin chemotherapy. Cis-diammine dichloroplatinum (DDP) 120 mg/m2 iv was given after prehydration, with mannitol diuresis on Day 1. On Day 3, an initial loading dose of Bleomycin 15 mg/m2 was given by rapid iv push followed by continuous 24 hour intravenous infusion of Bleomycin 15 mg/m2 Day 3 through Day 10. DDP 120 mg/m2 iv was administered again on Day 22. The patients were evaluated for tumor response and resectability between Day 29 to Day 35. Of 39 patients who were evaluable, there were 8 complete responses or CR (20%) and 22 partial responses or PR (56%), for a major response rate of 76%. Nineteen patients had surgery (14 patients whose lesions were initially inoperable and 5 patients who were initially operable). Chemotherapy toxicity in 40 patients included alopecia (40), vomiting (39), mucositis (11), skin rash (10), fever (17), weight loss of more than 5 lbs. (25), WBC less than 3,000 (2), platelets less than 100,000 (1), peak serum creatinine of 2 mg% (3), severe-hearing loss (1), hypersensitivity reaction (2). Surgical complication in 19 patients were pharyngocutaneous fistulae (2), wound dehiscence (1), meningitis and brain abscess (1). There was one death secondary to nephrotoxicity. This particular combination chemotherapy when given as initial treatment, appears very effective in reduction of tumor bulk. Long-term follow-up and randomization is necessary to determine effect upon survival.

Inverted papilloma and squamous cell carcinoma.

Since 1960, 15 patients with histologically proven inverted papilloma of the nose and paranasal sinuses have been treated at the University Hospital, City Hospital, and V. A. Hospital in Boston. Eight of these patients have been found to have squamous cell carcinoma in the pathological specimens; four of these patients have died of carcinoma. Wide surgical excision, usually through a lateral rhinotomy with exenteration of the invaded sinus as indicated, was the therapy of choice. In spite of the published incidence of carcinoma in inverted papilloma of approximately 7-24 per cent, we have found a much higher rate. We therefore, suggest that meticulous microscopic examination of multiple sections of inverted papilloma specimens be carried out in a search for evidence of squamous cell carcinoma. Inverted papilloma should be treated as a premalignant lesion by appropriate radical surgery.

Seeding of parotid carcinoma along Vim-Silverman needle tract.

A case report of seeding of parotid carcinoma along a core biopsy needle tract is presented. Excision of the needle biopsy site at the time of definitive surgery is recommended. Aspiration needle biopsy with a fine needle is reliable, with tumor seeding less likely.

Hemangiopericytoma of the parotid gland with a review of the literature.

Hemangiopericytoma, a rare vascular tumor characterized by pericytes, has been confused with benign lesions. The tumor cannot be identified clinically and requires histopathologic examination. Although the five year survival rate is good, the 10 year survival rate is poor for tumors in the head and neck region. Aggressive treatment with wide surgical margins appears warranted. Surgery in combination with radiotherapy has improved the poor prognosis. A case of hemangiopericytoma of the parotid gland, the eighth known in the surgical literature, is presented which illustrates the difficulty in the diagnosis and treatment of this lesion.