CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy camptothecin, is a newly developed water-soluble camptothecin derivative now undergoing phase-II evaluation. In an attempt to establish whether the combination of CPT-11 with other standard anti-cancer agents would be of any benefit, we studied the effects of CPT-11 in combination with 11 other anti-cancer agents on a human T-cell leukemia cell line, MOLT-3, in culture. We used both CPT-11 and SN-38 (active substance of CPT-11 in vivo), for our study. Cells were incubated for 3 days in the presence of 2 drugs (CPT-11 or SN-38 and another drug) and cytotoxic effects were determined by MTT assay. The effects of drug combinations on ID50 were analyzed by an improved isobologram method. Supra-additive and marginal supra-additive effects (synergism) were observed for CPT-11 in combination with cisplatin, cytosine arabinoside and mitomycin C. Additive effects were observed for its combination with amsacrine, bleomycin, doxorubicin, etoposide, 5-fluorouracil, mitoxantrone and vincristine. Alternate sub-additive and protective effects (antagonism) were observed for CPT-11 in combination with methotrexate. Similar tendencies were observed for SN-38 in combination with other agents. These results suggest that CPT-11 in simultaneous administration with a majority of anti-cancer agents has an advantage for cytokilling. Of these agents, cisplatin, cytosine arabinoside and mitomycin C are most suitable for simultaneous administration with CPT-11.

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Halitosis, defined as unpleasant oral odor, is a concern among the general public. Halitosis is generally diagnosed by organoleptic examination and by gas chromatographic analysis of the main source of halitosis, volatile sulfur compounds, such as hydrogen sulfide, methyl mercaptan, and dimethyl sulfide. Gas chromatography requires a large-scale system and a long running time. We investigated the use of a zinc-oxide thin film semiconductor sensor for measuring trace volatile sulfur compounds in mouth air. Mouth air samples collected in teflon bags from 21 volunteers were analyzed by 3 methods: the monitor analysis, gas chromatography, and organoleptic examination by 3 judges. The readings of the monitor were correlated with the values of the total volatile sulfur compounds measured by gas chromatography (r = 0.75, P < 0.01) and also with the organoleptic scores given by the judges (r = 0.76, P < 0.01). The organoleptic scores were correlated with the gas chromatographic values (r = 0.71, P < 0.01). These results suggest that this new monitor with a zinc-oxide thin film semiconductor sensor may be used for the diagnosis of halitosis. Its small size and simplicity of handling may enable its use for routine chair-side study and field surveys of halitosis.

Halitosis, defined as an unpleasant oral odor, has become a health concern among the general public. The objective of this study was to evaluate the diversity of clinical characteristics of halitosis of the patients who visited dental clinics. Sixty-eight patients with primary complaints of halitosis and 19 patients with primary complaints of periodontal diseases but secondary complaints of halitosis were studied by organoleptic examination. The patients with primary complaints were diagnosed as having halitosis in fewer cases than the patients with secondary complaints-25% and 53%, respectively. Patient complaints for halitosis were further categorized, by questionnaire, into three types: Type 1, self-conscious; Type 2, conscious by the indication of others; and Type 3, conscious by presumptions from the attitude of others. Although 80% of the patients of both groups were of Type 1, only 24.1% of the Type 1 patients with primary complaint, in comparison with 50% of the Type 1 patients with secondary complaint, were actually found to have halitosis. The results suggest that the majority of patients with primary complaints of halitosis at the dental clinic did not actually have halitosis, but suffered from an imaginary halitosis due to presumptions based upon others' attitudes. After treatment, these patients were more likely to be dissatisfied than patients who had visited the clinic with halitosis as their secondary complaint.

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A B S T R A C T The possible participation of proteases in superoxide (O°) production by human polymorphonuclear leukocytes (PMN) and monocytes was explored using various protease inhibitors and substrates. Protease inhibitors used included naturally occurring inhibitors of serine proteases and synthetic inhibitors that modify the active site of serine proteases. Substrates used were synthetic substrates of the chymotrypsin type as well as trypsin type ofprotease. All these inhibitors and substrates inhibited O2 production by human PMN and monocytes induced by cytochalasin E and concanavalin A, though PMN were more sensitive to these inhibitors and substrates than monocytes. Inhibition appeared rapidly even when the inhibitors were added at the same time as the stimulants, during the "induction time of O2 production" or at the time of maximum O2 production, whereas much greater inhibition was observed when the cells were preincubated with the inhibitors. These observations suggest that enzymatically active serine proteases are essential for these phagocytic cells to initiate and maintain the O2 production in response to the stimuli. The inhibitory effect of the inhibitor and substrate for chymotrypsin type protease was greater than that of those substances for trypsin-type protease. Macromolecular inhibitors also inhibited the O2 production.These findings suggest that the serine proteases involved in the O2 production by human PMN and monocytes are similar to chymotrypsin rather than trypsin, and are possibly located at the cell surface membrane.

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