Antitumor activity of interleukin-1 alpha and cisplatin in a murine model system.

BACKGROUND: Interleukin-1 alpha (IL-1 alpha) has potent antitumor activity either alone or combined with alkylating agents such as cisplatin and mitomycin C or porfiromycin. Cisplatin is an effective chemotherapeutic agent in the treatment of advanced squamous cell carcinoma of the head and neck (SCCHN). In the murine SCCVII/SF squamous cell carcinoma tumor model, IL-1 alpha induced acute hemorrhagic necrosis and increased clonogenic cell kill. OBJECTIVE: To determine the efficacy of cisplatin and IL-1 alpha, singly and in combination, in the treatment of SCCHN. METHODS: Syngeneic C3H/HeN mice were treated with single-dose, concurrent, intraperitoneal injections of cisplatin and interleukin-1 alpha 14 days after subcutaneous tumor implantation and were monitored for delayed tumor regrowth. RESULTS: Cisplatin alone, but not IL-1 alpha, induced significant delayed tumor regrowth when compared with control. The combination of IL-1 alpha and cisplatin was even more effective in delaying tumor regrowth than cisplatin alone. Fractional tumor volume was significantly reduced in animals treated with the combination of cisplatin and IL-1 alpha compared with those treated with IL-1 alpha alone. CONCLUSIONS: Results of interleukin-1 alpha and cisplatin dose-response experiments reveal that the combination of low-dose cisplatin and interleukin-1 alpha is more effective than high-dose cisplatin alone. Our data suggest that cisplatin and IL-1 alpha may be efficacious in the treatment of SCCHN.

The efficacy of topical antibiotic prophylaxis for contaminated head and neck surgery.

This study was undertaken to determine the feasibility of using perioperative topical antibiotics in contaminated head and neck surgery and to standardize the culture methodology (both qualitative and quantitative) which could serve as bacteriologic endpoints for evaluation. Following preliminary studies to establish oral cavity indicator organisms and the impact of a single antibiotic mouthwash dose on oral microflora, 10 consecutive patients undergoing contaminated head and neck surgery were recruited into a clinical trial where clindamycin mouthwash and intraoperative irrigation containing clindamycin were used instead of traditional parenteral antibiotics. The bacteriologic efficacy of topical clindamycin was assessed by comparing the presence of four indicator microorganisms (two aerobic and two anaerobic) cultured from two oral cavity culture sites before and after antibiotic prophylaxis. The patients included in the study underwent total laryngectomy plus neck dissection(s) for laryngeal or hypopharyngeal carcinoma from 1991 to 1992 at a large university hospital specializing in head and neck cancer surgery. The main outcome measures used were the development of a postoperative wound infection and quantitative and qualitative bacteriology of the intraoperative neck wound and postoperative oral cavity. Two aerobic and two anaerobic organisms proved useful as a practical indicator for bacteriologic efficacy. Preoperative mouthwash resulted in a 99% reduction of both aerobic and anaerobic bacteria in intraoperatively cultured neck sites. Irrigation during surgery with the clindamycin solution further reduced the bacterial neck counts by an additional 90%. There was a consistent overgrowth of Hemophilus species on postoperative oral cavity cultures. No patient developed a postoperative wound infection. A topical prophylactic antibiotic alone was efficacious and safe for patients undergoing major contaminated head and neck surgery. Culture methods for assessment of bacteriologic efficacy were reproducible and cost-effective. This pilot study furnishes the ethical and scientific basis for large-scale prospective trials comparing topical versus parenteral antimicrobial agents.

Treatment of idiopathic sudden sensorineural hearing loss.

A retrospective review was done, examining the charts of 41 patients admitted to The Eye and Ear Hospital of Pittsburgh with a diagnosis of sudden hearing loss (SHL). Treatment consisted of (1) systemic steroids; (2) daily intravenous histamine infusion; and (3) carbogen (95% oxygen and 5% CO2) inhalation. Parameters examined included age, sex, duration of symptoms prior to admission, days hospitalized, side of lesion, vestibular symptoms, tinnitus, blood work, radiography, vestibular function (ENG), and serial audiograms. Fifty-four percent showed improvement in hearing, defined as at least a 10-dB increase at any frequency following therapy. There was no correlation of preexisting signs, symptoms, or findings with hearing recovery. Since the natural history of this process demonstrates spontaneous improvement in approximately two thirds of patients without treatment, we conclude that for the group of patients that we treated, our therapeutic regimen was ineffectual.