Phase II study of accelerated fractionation radiation therapy with carboplatin followed by PCV chemotherapy for the treatment of anaplastic gliomas.

PURPOSE: To conduct a Phase II one-arm study to evaluate the long-term efficacy and safety of accelerated fractionated radiotherapy combined with i.v. carboplatin for patients with previously untreated anaplastic gliomas. METHODS AND MATERIALS: Between 1988 and 1992, 90 patients received 1.9-2.0-Gy radiation 3 times a day with 2-h infusions of 33 g/m(2) carboplatin for two 5-day cycles separated by 2 weeks. After radiotherapy, patients received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or until the tumor progressed. RESULTS: Ninety patients were evaluable for analysis. Histologically, 69 had anaplastic astrocytoma; 14, anaplastic oligoastrocytoma; and 7, anaplastic oligodendroglioma. Gross total resection was performed in 20 (22%), subtotal resection in 45 (50%), and biopsy in 25 (28%); reoperation (total or subtotal resection) was performed in 50 (56%) patients. A multivariate analysis showed that a younger age (p = 0.026), Karnofsky performance score (KPS; p = 0.009), and brain necrosis (p = 0.0002) were predictive of a better survival. Results from analysis of extent of surgery (biopsy, subtotal resection, gross total resection) approached significance (p = 0.058). Radiation dose, irradiated tumor volume, and techniques used (boost and fields) were not significant variables. The median survival (MS) of all anaplastic glioma patients was 28.1 months; for anaplastic astrocytoma patients, MS was 28.7 months and 40.8 months for the combined anaplastic oligodendroglioma/oligoastrocytoma patients. Long-term survival occurred in 25% of anaplastic glioma patients who were alive 8.6 years after treatment was initiated. Treatment-induced necrosis was documented by surgery or autopsy in 19 (21%) patients; 21 (23%) had a mixed pattern of necrosis and tumor; and an additional 13 (14%) patients who did not have surgical or autopsy demonstration of predominant radiation necrosis had magnetic resonance imaging (MRI) evidence of radiation necrosis. Serious clinical neurologic deterioration and/or dementia requiring full-time caregiver attention were observed in 9 (10%) patients. CONCLUSION: When comparable selection criteria are applied, the rate of MS in this study is inferior to results attainable with current radiation and chemotherapy approaches, although the rates of long-term survival are comparable. Theoretically, patients failing therapy and dying earlier than anticipated may be because of excessive central nervous system (CNS) toxicity resulting from the combination of accelerated fractionated irradiation, intensive carboplatin chemotherapy before each radiation fraction, and postirradiation PCV chemotherapy. On the other hand, patients with treatment-induced necrosis survived significantly longer than patients who did not demonstrate MRI or histologic evidence of necrosis (MS, 106 months vs. 18-33 months).

Phase III randomized study of postradiotherapy chemotherapy with alpha-difluoromethylornithine-procarbazine, N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosurea, vincristine (DFMO-PCV) versus PCV for glioblastoma multiforme.

Although the efficacy of the nitrosourea-based combination chemotherapy procarbazine, N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosurea, and vincristine (PCV) has been previously demonstrated in the setting of anaplastic/intermediate-grade gliomas, the benefit for glioblastoma patients remains unproven. In the current study, we sought to determine whether the addition of alpha-difluoromethylornithine (eflornithine), an inhibitor of ornithine decarboxylase, which has shown encouraging results in the setting of recurrent glioma patients, to a nitrosourea-based therapy (PCV) would constitute a more effective adjuvant therapy in the treatment of glioblastoma multiforme patients in the postradiation therapy setting. Following conventional radiation therapy, 272 glioblastoma (GBM) patients were randomized to receive either alpha-difluoromethylornithine-PCV (DFMO-PCV; 134 patients) or PCV alone (138 patients), with survival and time to tumor progression being the primary endpoints. The starting dosage of DFMO was 3.0 g/m2 p.o. q8h for 14 days before and after treatment with N-(2-chloroethyl)-N-cyclohexyl-N-nitrosurea; PCV was administered as previously described1. Clinical and radiological (Gadolinium-enhanced MRI) follow-ups were nominally at the end of each 6 or 8 week cycle (PCV at 6 weeks; DFMO-PCV at 8 weeks). Laboratory evaluations for hematologic and other adverse effects were at 2 week intervals. There was no difference in median survival or median time-to-tumor progression between the two treatment groups, as measured from day of commencement of postradiotherapy chemotherapy [MS (months): DFMO-PCV, 10.5; Overall survival, as measured from time of tumor diagnosis at first surgery, was 13.3 and 14.2 months at the median and 6.2 and 8.7% at 5 years, respectively, for the DFMO-PCV and PCV arms. The treatment effect was unchanged after adjustment for age, performance status (KPS), extent of surgery, and other factors using the multivariate Cox proportional hazard model. Adverse effects associated with DFMO consisted of gastrointestinal (diarrhea nausea/vomiting), cytopenias, and minimal ototoxicity (limited to tinnitus) at the dose range tested. The addition of DFMO to the nitrosourea-based PCV regimen in this phase III study demonstrated no additional benefit in glioblastoma patients, underscoring the resistance of glioblastoma multiforme tumors to alkylating agents. For patients with anaplastic (intermediate grade) gliomas, in which the previously demonstrated benefit of post-radiation chemotherapy is more substantial, the evaluation of DFMO-PCV vs. PCV is still ongoing and hopefully will yield more encouraging results.

Thymidine dinucleotides inhibit contact hypersensitivity and activate the gene for tumor necrosis factor alpha1.

DNA is a target for ultraviolet-B-induced inhibition of contact hypersensitivity, and small DNA fragments such as thymidine dinucleotides (pTpT) can simulate several ultraviolet-induced effects. To determine whether pTpT mimics the suppressive influence of ultraviolet-B on contact hypersensitivity, we compared the effects of topical application of pTpT with those of ultraviolet-B irradiation on C57BL/6 mice sensitized to dinitrofluorobenzene. Mice pretreated with pTpT or ultraviolet-B irradiation showed markedly suppressed ear swelling responses to dinitrofluorobenzene challenge. Because tumor necrosis factor alpha mediates ultraviolet-B-induced suppression of contact hypersensitivity, and because pTpT exerts many ultraviolet-mimetic effects by augmenting mRNA and protein levels of effector molecules, we asked if pTpT mimics ultraviolet-B's upregulatory influence on tumor necrosis factor alpha expression. Using transgenic mice carrying a chloramphenicol acetyl transferase reporter linked to the tumor necrosis factor alpha promoter, we examined effects of ultraviolet-B irradiation versus intradermal injection of pTpT on tumor necrosis factor alpha gene transcription. Both treatments induced cutaneous chloramphenicol acetyl transferase activity. Ultra- violet-B or pTpT treatment of cultured dermal fibroblasts from these mice also stimulated chloramphenicol acetyl transferase activity. To determine whether human cells responded similarly, a well- differentiated ultraviolet-responsive human squamous cell carcinoma line was treated with pTpT. pTpT increased tumor necrosis factor alpha mRNA expression and protein secretion in a dose-dependent manner. Our findings expand the spectrum of ultraviolet effects mimicked by pTpT to include inhibition of contact hypersensitivity and activation of the tumor necrosis factor alpha gene. These results support the hypothesis that DNA photoproducts and/or their repair intermediates trigger many of the biologic consequences of ultraviolet irradiation.

Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials.

PURPOSE: To determine aggregate outcomes and prognostic covariates in patients with recurrent glioma enrolled onto phase II chemotherapy trials. PATIENTS AND METHODS: Patients from eight consecutive phase II trials included 225 with recurrent glioblastoma multiforme (GBM) and 150 with recurrent anaplastic astrocytoma (AA). Their median age was 45 years (range, 15 to 82 years) and their median Karnofsky performance score was 80 (range, 60 to 100). Prognostic covariates were analyzed with respect to tumor response, progression-free survival (PFS), and overall survival (OS) by multivariate logistic and Cox proportional hazards regression analyses. RESULTS: Overall, 34 (9%) had complete or partial response, whereas 80 (21%) were alive and progression-free at 6 months (APF6). The median PFS was 10 weeks and median OS was 30 weeks. Histology was a robust prognostic factor across all outcomes. GBM patients had significantly poorer outcomes than AA patients. The APF6 proportion was 15% for GBM and 31% for AA, whereas the median PFS was 9 weeks for GBM and 13 weeks for AA. Results were also significantly poorer for patients with more than two prior surgeries or chemotherapy regimens. CONCLUSION: Histology is a dominant factor in determining outcome in patients with recurrent glioma enrolled onto phase II trials. Future trials should be designed with separate histology strata.

Contralateral coronoid process bone grafts for orbital floor reconstruction: an anatomic and clinical study.

PURPOSE: This study compares the contour of the coronoid process with the orbital floor using skulls and shows the use of this bone as a graft for orbital floor reconstruction. METHODS: Measurements and contour evaluations of the orbital floor and the contralateral mandibular coronoid process (12 right orbital floors with the lateral surface of the left coronoid process and 12 left orbital floors with the lateral surface of the right coronoid processes) were made in 24 dried adult human skulls (age, race, gender unknown) to assess the feasibility of using the mandibular coronoid process for orbital floor reconstruction. Applying the findings of this study, eight patients who had sustained either an isolated orbital floor blowout fracture (n = 2) or orbital floor compromise with an associated zygomatic bone fracture (n = 6) were treated by using their contralateral coronoid process for repair of the orbital floor. RESULTS: Anatomic Study: Measurements and contour comparisons of the right orbital floor with the left lateral cortex of the coronoid process in 12 skulls and the left orbital floor with the right lateral cortex of the coronoid process in the another 12 skulls showed a close match in contour and demension. CLINICAL STUDY: Although minimal trimming of the peripheral bony margins and medial coronoid cortical plate was needed, none of the grafts required recontouring of their lateral cortical surface in the eight patients. Postoperative radiographic studies showed a correct anatomic contour of the orbital floor. A 1-year follow-up of each patient showed no occurrence of diplopia, enophthalmia, muscle entrapment, or infection. All eight patients had transient (1 to 2 weeks) trismus. CONCLUSION: Based on the anatomic studies and clinical results, the coronoid process makes an excellent donor graft site for reconstruction of orbital floor deformities.

The treatment of recurrent cerebral gliomas with all-trans-retinoic acid (tretinoin).

Malignant gliomas continue to be a significant source of mortality in young and middle aged adults. The introduction of new treatment strategies and multidisciplinary approaches has improved the outcome of patients with these tumors only slightly. Because retinoic acid has growth inhibitory activity against glioma and neuroblastoma cells in cultures, we assessed the efficacy of all-trans-retinoic acid in the treatment of recurrent cerebral gliomas. Thirty-six patients with recurrent cerebral gliomas were entered in the study and treated with 120 or 150 mg/ m2/day of all-trans-retinoic acid as a single agent. The drug was given for 3 weeks followed with one week of rest. Two blocks of 4 weeks constituted one course of treatment. One (3%) of 34 evaluable patients had a minor response and 14 (41%) had stable disease. In the rest of the patients (56%), tumors continued to progress despite treatment. The median time to progression of all evaluable patients was 8 weeks, and for the responders was 17 weeks. The higher dose level (150 mg/m2) was associated with high incidence of headache, which responded to dose reduction. The lower dose level was very well tolerated, with mild, mainly dermatological toxicity. All-trans-retinoic acid as a single agent has no significant activity against recurrent cerebral gliomas.

Comparison of dental water quality management procedures.

The effectiveness of ADA-recommended approaches for reducing dental unit waterline, or DUWL, contamination was investigated using newly installed dental units. Over a 2-month period, the authors studied independent water reservoirs, a sodium hypochlorite disinfection regimen, daily draining and purging of DUWLs and point-of-use filters by assessing microbial contamination and biofilm development using scanning electron microscopy. The findings demonstrate that DUWL contamination can be controlled when dental personnel use available technologies and adhere to recommended maintenance protocols.

Treatment of recurrent malignant gliomas with high-dose 13-cis-retinoic acid.

Malignant gliomas account for more than 60% of all primary brain tumors in adults. Adjuvant chemotherapy in addition to radical surgery and radiation therapy has provided only a modest increase in survival. Retinoic acid has been shown to have growth-inhibitory activity against glioma cells in culture. This provides the rationale for a Phase II study using 13-cis-retinoic acid (CRA) in patients with recurrent malignant brain tumors. The objective of this study was to determine the clinical activity of CRA in patients with a histologically proven diagnosis of malignant brain tumor and documented progressive or recurrent disease after radiation and chemotherapy. Fifty patients with documented recurrent disease were treated with CRA as a single agent p.o. at a dose of 60-100 mg/m2 per day. Three weeks of treatment were followed by 1 week of rest. Of the 43 patients who received more than 4 weeks of therapy, 3 (7%) achieved partial response, 7 (16%) achieved minor response, 13 (30%) remained stable, and 20 (47%) had disease progression. The median time from onset of treatment to disease progression for the whole group of 43 patients was 16 weeks (19 weeks for glioblastomas and 11 weeks for anaplastic glioma), whereas that for the 23 patients with partial response and minor response and who remained stable was 66 weeks, and that for the 20 patients with progressive disease was only 8 weeks. The median survival time for glioblastoma was 58 weeks, and 34 weeks for anaplastic astrocytoma. Toxicity was mainly dermatological, with dry skin and cheilitis. These preliminary results suggest that 13-cis-retinoic acid is active against malignant gliomas and is very well tolerated.

Combination of 6-thioguanine, procarbazine, lomustine, and hydroxyurea for patients with recurrent malignant gliomas.

OBJECTIVE: To determine the efficacy of the combination of 6-thioguanine, procarbazine, lomustine, and hydroxyurea for patients with recurrent malignant gliomas after failure of either previous radiotherapy alone or previous radiotherapy plus nitrosourea-based chemotherapy. METHODS: Seventy-seven patients with recurrent malignant gliomas were studied. 6-Thioguanine was administered for 4 days before lomustine, and procarbazine was administered for 1 day before and 2 days after lomustine to potentiate lomustine's antitumor effect. Hydroxyurea was initiated 1 day before lomustine and continued for a total of 3 days. RESULTS: Thirty patients with glioblastomas and 47 patients with anaplastic gliomas were eligible for evaluation. In the glioblastoma group, 2 of 30 patients had a partial response and 8 of 30 patients had stable disease. This group of patients who responded and had stable disease included 6 of 10 patients who had not undergone previous chemotherapy but only 4 of 20 who had undergone previous chemotherapy. The overall median time to disease progression for the glioblastoma group was 9 weeks. In the anaplastic glioma group, 11 of 47 patients had a partial response and 25 of 47 had stable disease, including 23 of 30 without previous chemotherapy and 13 of 17 who had undergone previous chemotherapy. The median time to disease progression for the whole anaplastic glioma group was 24 weeks; however, the time to disease progression was 50 weeks for responding patients who had not undergone previous chemotherapy and 25 weeks for those who had undergone previous chemotherapy. CONCLUSION: Our results indicate that chemotherapy with a combination of 6-thioguanine, procarbazine, lomustine, and hydroxyurea is active for patients with recurrent anaplastic gliomas and glioblastomas not previously treated with nitrosourea-based chemotherapy but is inactive for patients with glioblastomas previously treated with chemotherapy.

MR of toxic effects of accelerated fractionation radiation therapy and carboplatin chemotherapy for malignant gliomas.

PURPOSE: To present MR findings of parenchymal brain injury after accelerated fractionation radiation therapy combined with carboplatin chemotherapy in the treatment of malignant brain gliomas. METHODS: Eighty-one evaluable subjects in an ongoing treatment protocol for malignant gliomas form the patient base for this report. After surgical resection of tumors, patients underwent a course of accelerated fractionation radiation therapy to a total dose of 60 Gy. Carboplatin was infused intravenously before each radiation treatment. Precontrast and postcontrast MR scans were obtained before treatment and at 4-week intervals afterward and were analyzed retrospectively. RESULTS: Posttreatment MR imaging in 20 of the 81 patients showed development of unusual parenchymal lesions or enlarging masses needing debulking, and these patients underwent second operations. Two groups emerged: those with tumor and necrotic brain (n = 11) and those with necrosis and reactive gliosis but no definitive tumor (n = 9). Enhancing lesions in the tumor-negative group appeared later than those in the tumor-positive group, were often multiple, and were usually located several centimeters away from the tumor resection site or even contralaterally. Common locations were the corpus callosum and corticomedullary junctions. Lesions in the tumor-positive group were more often solitary and located immediately adjacent to the surgical site. Positive and negative results of positron emission tomography with fludeoxyglucose F 18 were obtained in both groups. The incidence of brain necrosis without associated tumor was 11%. CONCLUSIONS: A pattern of unusual enhancing parenchymal brain lesions was seen on MR imaging after accelerated fractionation radiation therapy and concomitant carboplatin chemotherapy. The abnormalities seem more extensive than focal necrotic lesions on enhanced CT or MR imaging after conventional radiation therapy, and they may mimic recurrent tumor.

Densitometric properties of rapid manual processing solutions: abbreviated versus complete rapid processing.

Rapid manual processing solutions produce wet, readable radiographs in 1 to 2 min. However, some manufacturers permit time reductions for various processing steps to obtain images even more quickly. Differences in densitometric characteristics and spatial resolution between abbreviated rapid processing (ARP) and complete rapid processing were examined in four rapid manual processing systems on D- and E-speed film. When compared with films processed conventionally in an automatic processor, films processed in rapid manual processing chemistries had more fog and generally lower levels of speed and contrast. ARP radiographs were excessively stained unless they were washed for at least 60 s after fixing. The most severe depreciation in ARP film quality occurred when developing time was reduced by 50%; the complete rapid processing developing time should always be used. E-speed films produced radiographs with comparable densitometric and resolution characteristics to D-speed films for ARP and complete rapid processing techniques while requiring 40% less radiation.

Sixteen years of experience with sterilization monitoring.

Sterilization in the dental office should be monitored to ascertain proper sterilizer function. Biologic monitoring with calibrated preparations of bacterial spores is the preferred, as well as the only method that actually measures sterilization. A dental school-based sterilization monitoring service for dental practices was established in 1978 at the University of Detroit. This service has grown from 20 participating dental offices to more than 1,500. In 1993, 18,137 biologic monitoring tests were performed. The participants in the service primarily use autoclaves (70%) for heat sterilization, while unsaturated chemical-vapor sterilizers (20%) and dry-heat units (10%) are less common. This article describes the history of sterilization monitoring in dental practices from 1978 to the present through a dental school-based service.

The treatment of anaplastic oligodendrogliomas and mixed gliomas.

We evaluated the treatment outcome of 17 patients with anaplastic oligodendroglioma and 17 patients with anaplastic mixed oligodendroglioma-astrocytoma. In the anaplastic oligodendroglioma group, eight patients were treated at the time of the initial admission with radiotherapy and adjuvant chemotherapy, and nine patients were treated at the time of recurrence with salvage chemotherapy. Three patients for whom adjuvant chemotherapy was not successful were also treated with chemotherapy at the time of recurrence. In the initial group, one patient had complete response, three had partial responses, and 4 had stable disease (response and stable disease, 100%), but all except one progressed within 10 months. Of the 12 patients who received chemotherapy during recurrence, there was 1 complete response, 2 partial responses, and 6 stable disease (response and stable disease, 75%), with long response duration and long survival (15-132+ mo). In the anaplastic mixed oligodendroglioma-astrocytoma group, 12 patients were treated at the time of the initial admission and 6 patients treated at the time of recurrence. The initial treatment resulted in two complete responses, three partial responses, and seven stable disease (response and stable disease, 100%), with most responses lasting longer than 12 months. The treatment of the patients with recurrent disease resulted in one partial response and five stable disease (response and stable disease, 100%), with a median time to progression of 6 months. These results suggest that aggressive treatment is beneficial for recurrent anaplastic oligodendrogliomas and mixed gliomas as well as initial mixed gliomas but may offer only minimal advantage over conventional radiotherapy for the initial treatment of anaplastic oligodendrogliomas.

Treatment of recurrent gliomas with eflornithine.

BACKGROUND: Oral eflornithine in combination with intravenous mitoguazone (methylbisguanylhydrazone) has shown activity against recurrent anaplastic gliomas. Eflornithine alone, however, has not been evaluated against recurrent gliomas. PURPOSE: This study compared the antitumor activity of oral eflornithine with that of oral eflornithine combined with intravenous mitoguazone in the treatment of patients with recurrent or progressive glioblastoma multiforme as well as nonglioblastoma anaplastic gliomas. METHODS: During the 1st year of therapy with eflornithine alone, the drug was given at a dose of 3.6 g/m2 on days 1-14, 22-35, and 43-56 every 8 hours; cycles were repeated every 63 days until progression. For the 2nd year, the drug was given on days 1-14, 29-42, and 57-70, with 84 days between cycles. For the 1st and 2nd years of eflornithine-mitoguazone therapy, eflornithine was given at 1.8 g/m2 on the same schedule. Mitoguazone was given intravenously at 200 mg/m2 on the final day of each 2-week sequence of eflornithine therapy. Response was determined by evaluating changes in the size of contrast-enhanced neuroimages. RESULTS: Because of two cases of lethal hepatic necrosis, the initial random allocation of patients to the eflornithine-mitoguazone arm was stopped after 23 patients had been accrued. Ninety-eight patients were entered in the eflornithine arm; 80 patients (36 glioblastoma multiforme patients and 44 anaplastic glioma patients) were assessable for response. Antitumor activity (partial response, minor response, and stable disease) was seen in 45% of the patients with anaplastic gliomas, for a median of 49 weeks, but in only 17% of patients with glioblastoma multiforme (median not attained). Twenty-one (20%) of the patients with anaplastic glioma and 33% of the patients with glioblastoma multiforme were removed from the study before completing the first 8-week course of therapy because of neurological deterioration and tumor progression by the 5th week of treatment. CONCLUSION: This study suggests that eflornithine alone is an effective palliative therapy for recurrent anaplastic gliomas. Additional studies are needed to confirm our finding.

Effectiveness of dental office instrument sterilization procedures.

To evaluate instrument sterilization procedures in Minnesota, biological indicators were used to monitor 406 sterilizers in 381 dental offices. Findings suggest a general improvement in instrument performance over that of a decade ago, but sterilization failure rates are still too high. Sterilizer operator errors are a major cause of sterilization failures. BIs are useful in monitoring sterilization performance only when sterilization procedures are performed consistently and competently by well-trained staff using adequately maintained equipment.

Intravenous carboplatin for recurrent malignant glioma: a phase II study.

Thirty patients with recurrent malignant glioma were treated with intravenous (IV) carboplatin (CBDCA) every 4 weeks at a starting dose of 400 mg/m2 escalating to 450 mg/m2. All patients had documented recurrent tumor after prior radiotherapy but had not received prior chemotherapy. Of 29 assessable patients, four (14%) responded to the treatment for 44, 51+, 72, and 91 weeks; 10 (34%) achieved stable disease (S); while 15 (52%) had progressive disease (P). The total response (responses plus S) rate was 48%, with a median time to progression (MTP) of 26 weeks in these patients; the MTP for all 29 patients was 11 weeks. The toxic effects were mainly hematologic, with thrombocytopenia and granulocytopenia being mild at 400 mg/m2 and 450 mg/m2 doses. NO neurotoxicity or renal toxicity was encountered. These results suggest that CBCDA given at 400 mg/m2 or 450 mg/m2 every 4 weeks is marginally active in patients with recurrent malignant gliomas. Since hematologic toxicity is mild, a higher dose could possibly be given, and may increase the response rate.

Epidermal toxicity of disinfectants.

The purpose of the present study was to investigate the capacity of various disinfectant chemicals to cause epithelial toxicity with repeated exposure. The abdominal area of 3-month old, experimental ICR/CD-1 mice was initially shaved, denuded with a depilatory agent and allowed to rest for 24 hours. Commercial preparations of iodophors, bleach, synthetic phenols, phenolic/alcohols, and glutaraldehydes were then sprayed onto the exposed abdominal tissue 8 times/day (0.8 ml spray) for 2 consecutive days. The applied disinfectant was allowed to dry between procedures. In comparison to controls sprayed with distilled water, each disinfectant stimulated some degree of epidermal changes. Resultant multiple brownish lesions showed local thickening and hardening. Histologically, epidermal changes ranged from mild hypertrophy to extensive epithelial erosion. A few inflammatory cells were occasionally detected in the epithelium. When present, dermal reactions ranged from a mild inflammation to focal areas of collagen degeneration. The results indicated that iodophors stimulated the mildest reactions, followed by the synthetic phenol preparations, bleach, phenolic/alcohols, and glutaraldehyde sprays. Similar assays using glutaraldehyde immersion sterilants/disinfectants produced marked tissue destruction.