Toxicity of intrapleural Bacillus Calmette-Guérin treatment in animals.

The toxicity of intrapleural Tice strain Bacillus Calmette-Guérin (BCG) infection was tested in hamsters. Doses above 10(6) colony-forming units caused significant systemic infection, which could be controlled with conventional antituberculosis therapy. Living BCG in the pleural space did not prevent the healing of bronchial or vascular closures after pulmonary resection. Prophylactic intrapleural BCG (10(6) colony-forming units) significantly reduced tumor growth in the lungs of mice following i.v. injection of 5 x 10(5) syngeneic sarcoma cells. These animal experiments suggest that intrapleural BCG may be administered in the pleural space after lung resection in limited doses if followed by a complementary course of antimicrobial therapy.

Mycotic wound infections. A new challenge of the surgeon.

Fungal wound infections have become more common because of the increased use of immunosuppressive and antineoplastic agents, prosthetic devices and grafts, broad-spectrum antibiotics, and hyperalimentation. Severe burns, renal failure, and other debilitating conditions also predispose to invasive mycoses. An aggressive diagnostic approach is particularly important, and tissue biopsy specimens are often necessary to establish a diagnosis. Meticulous surgical technique and minimization of the predisposing factors are crucial in the prevention of these infections, and prophylactic antimycotic agents may be of value in selected high-risk patients. Some mycotic wound infections can be managed effectively without systemic therapy; but when systemic agents are needed, combination antifungal therapy may provide improved results without increased drug toxicity.

Combined amphotericin B-flucytosine therapy in Aspergillus pneumonia.

The incidence of aspergillosis is increasing while the prognosis remains dismal. Standard single-drug therapy with amphotericin B offers unacceptably low cure rates. A patient with Aspergillus pneumonia was treated with a synergistic combination of amphotericin B and flucytosine. A prompt clinical response and progressive resolution of the infection were observed. Combination therapy appeared to decrease the dose of amphotericin B needed for effective therapy. It may provide improved results with decreased toxic effects.

Recent advances in the treatment of systemic mycotic infections.

Serious therapeutic problems are posed by the increasing incidence of invasive fungal infections in transplant recipients as well as in patients with compromised immune defenses, prosthetic devices and grafts and several other predisposing factors. A number of new approaches, including combination drug treatment and the development of newer agents, may justify increased optimism in the management of these infections.

BCG immunotherapy: effects of dose and route of administration on survival of mice bearing established tumors.

Bacillus Calmette-Guérin (BCG) was administered in various doses by four different routes to C3H/HeJ mice bearing well-established syngeneic MC-42 fibrosarcomas. Injections of BCG into established primary tumors decreased survival of tumor-bearing mice as compared to saline-injected controls. Of the three dosage groups, high-dose (10(8) viable organisms) intralesional BCG was most detrimental. The injection of low-dose BCG (10(4) organisms) into established tumors or subcutaneously at a distant site also shortened host survival times. Other subcutaneous injections and injections of BCG into the peritoneal or pleural cavities had no significant effect on survival, regardless of dosage. The dose-dependent effects of BCG immunotherapy which may prolong or shorten survival are discussed.

Possible active enhancement of a human cadaver renal allograft with antilymphocyte serum (ALS) and donor bone marrow: case report of an initial attempt.

Nonspecific immunosuppression of transplant patients frequently leads to complications which might be circumvented by inducing donor-specific immune unresponsiveness. Such specific immunosuppression has been produced experimentally, with use of donor antigen and antilymphocyte serum (ALS) for active enhancement. A case is presented in which the recipient of a cadaveric renal allograft (zero antigen match, cross-match negative) was given ALS (first 14 days after operation) and 11 X 10(9) donor bone marrow cells (twenty-fifth postoperative day) along with conventional doses of prednisone and Imuran in an attempt to produce donor-specific immune unresponsiveness. There were no rejection episodes, and serum creatinine remained less than 1.0 mg. per 100 ml. By the second month after transplantation there was no evidence for the persistence of donor erythrocytes or white cells. The conventional immunosuppressive agents were tapered and renal function was normal 8 months after transplantation, when the patient developed fatal peritonitis secondary to perforated sigmoid diverticulitis. At autopsy the renal allograft showed only minimal evidence of rejection. The present case illustrates an attempt to use ALS and donor bone marrow cells for active enhancement of a human cadaveric renal allograft. The infusion of stored donor marrow cells after transplantation is a particularly applicable technique for human cadaveric organ transplantation. The rejection-free course of this patient suggests that attempts to produce active enhancement clinically deserve further trial.

Survey of the current status of the clinical uses of antilymphocyte serum.

A limited degree of effectiveness of antilymphoid globulin in clinical kidney and bone marrow transplantation has been described. It may also be useful for the prolongation of temporary skin allografts for burn patients and may be valuable as an adjunct in the treatment of certain autoimmune diseases. The use of antilymphoid globulin with donor antigen to facilitate allograft enhancement has been reviewed. An instance of possible enhancement of a mismatched cadaveric renal allograft in a highly sensitized recipient given antilymphoid globulin and donor marrow is recorded. Use of antilymphoid globulin to facilitate enhancement with donor antigen is probably the next major application of antilymphoid globulin.

Immunological detection of human bladder carcinoma.

A rabbit antiserum (RABCa) to membrane antigenic extracts of human bladder carcinomas was produced. RABCa failed to detect bladder cancer-specific antigens in gel diffusion reaction against antigenic extracts of bladder carcinoma and normal bladder mucosa. However, RABCa showed higher complement fixation activity against urines from bladder cancer patients compared with normal urines. The micro-complement fixation (CF) assay (108 patients) was positive in 17 of 27 bladder cancer patients (62.9%) compared to only 1 of 29 normals (3.4%). However, 10 of 11 patients with urinary infections also were positive. A micro-Ouchterlony agar gel diffusion assay was also used to study urine samples (118 patients). RABCa produced separate precipitin bands against 20 of 30 bladder cancer urines (66.7%) while only 1 of 24 normal urines gave these bands (4.2%). Again, infected urines were positive (9 of 11). Additionally, urine from patients with benign urological disease was often positive in CF (11 of 41) and Ouchterlony (15 of 43) assays. RABCa serum was absorbed with normal bladder mucosa membrane extracts either once (1X) or three times (3X) to increase the specificity of the Ouchterlong gel diffusion assay. Using RABCa (1X) the per cent of positive bladder cancer urines and normals decreased only slightly, while the number of positive reactions against benign urological disease urines dramatically decreased (17.9%). RABCa (3X) further reduced the per cent of positive reactions with benign urological disease urines (10.3%), greatly reduced the reactivity with infected urines (60.0%), and gave no positive reactions with normal urines, without significantly decreasing the abiltiy to detect bladder carcinoma (51.9%). Although RABCa was 100% effective in detecting high grade (III) bladder tumors, almost two-thirds of all transitional cell papilloma urines were also positive. The nature of the material detected in bladder cancer and infected urines by RABCa is probably a product of in vivo inflammation. It does not appear to be part of the bacterial cell membrane or a bacterial metabolite. CEA (up to 10 ng/ml) did not produce positive precipitin bands with RABCa. Sephadex G-100 fractionation of urines suggests that RABCa reacts in the CF and Ouchterlony assays with a component or urine which has a molecular weight greater than 100,000-200,000 M.W. In summary, an antiserum has been prepared which may be used in micro-complement fixation and micro-Ouchterlony agar gel diffusion assays for immunological screening in the early detection of clinical disease, especially bladder cancer and urinary infection.