Monitoring of singlet oxygen is useful for predicting the photodynamic effects in the treatment for experimental glioma.

PURPOSE: Singlet oxygen ((1)O(2)) generated in photodynamic therapy (PDT) plays a very important role in killing tumor cells. Using a new near-IR photomultiplier tube system, we monitored the real-time production of (1)O(2) during PDT and thus investigated the relationship between the (1)O(2) production and photodynamic effects. EXPERIMENTAL DESIGN: We did PDT in 9L gliosarcoma cells in vitro and in an experimental tumor model in vivo using 5-aminolevulinic acid and nanosecond-pulsed dye laser. During this time, we monitored (1)O(2) using this system. Moreover, based on the (1)O(2) monitoring, we set the different conditions of laser exposure and investigated whether they could affect the tumor cell death. RESULTS: We could observe the temporal changes of (1)O(2) production during PDT in detail. At a low fluence rate the (1)O(2) signal gradually decreased with a low peak, whereas at a high fluence rate it decreased immediately with a high peak. Consequently, the cumulative (1)O(2) at a low fluence rate was higher, which thus induced a strong photodynamic effect. The proportion of apoptosis to necrosis might therefore be dependent on the peak and duration of the (1)O(2) signal. A low fluence rate tended to induce apoptotic change, whereas a high fluence rate tended to induce necrotic change. CONCLUSIONS: The results of this study suggested that the monitoring of (1)O(2) enables us to predict the photodynamic effect, allowing us to select the optimal laser conditions for each patient.     

Brain acetylcholinesterase activity in Alzheimer disease measured by positron emission tomography

Brain acetylcholinesterase activity was measured in 14 patients with Alzheimer disease and 14 age-matched control subjects by positron emission tomography with a radioactive acetylcholine analogue. Kinetic analysis was performed to calculate k3, an index of acetylcholinesterase activity. The k3 values were significantly reduced in the neocortex, hippocampus, and amygdala of all patients with Alzheimer disease, suggesting a loss of cholinergic innervation from the basal forebrain. Most profound reductions of k3 values were observed in the temporal (-30%) and parietal cortices (-31%), although reductions of k3 values were relatively uniform in the cerebral neocortex. This technique may be a powerful tool for early diagnosis of Alzheimer disease and also for therapeutic monitoring of acetylcholinesterase inhibitors in Alzheimer disease.     

Treatment of rat experimental brain tumors by herpes simplex virus thymidine kinase gene-transduced allogeneic tumor cells and ganciclovir

Transfer of the herpes simplex virus thymidine kinase (HSVtk) gene, followed by administration of ganciclovir (GCV), generates the "bystander effect," in which HSVtk-negative wild-type cells are killed by GCV, as are HSVtk-expressing cells. Our previous study demonstrated that intracranial 9L gliomas could be efficiently treated due to this bystander effect by injecting the 9L glioma cells transduced with the HSVtk gene in the vicinity of the preimplanted wild-type 9L glioma and then administering GCV. For a possible clinical application of the bystander effect-mediated cell killing, we tested HSVtkgene-transduced allogeneic C6 glioma cells (C6tk) instead of syngeneic 9L glioma cells transduced with the HSVtk gene. Fisher rats were implanted intracranially with wild-type 9L glioma cells, subsequently injected with C6tk cells at the same brain coordinate, and thereafter treated with GCV or saline. When the rats were treated with GCV, a significant retardation of tumor growth was observed by serial magnetic resonance imaging, although this growth retardation was less prominent than that observed with 9L glioma cells transduced with the HSVtk gene; consequently, survival was prolonged (P < .01). Tumors that received C6tk cells contained almost no HSVtk-positive cells after treatment with GCV. Rejection of allogeneic tumor cells, although possibly incomplete in the brain, can also contribute to the safety of this therapeutic strategy.     

Demonstration of abnormal perfusion in the pons with high resolution SPECT and Technetium-99m HMPAO in a patient with acoustic neuroma

We detected a regional defect in the pons with ipsilateral cerebellar hypoperfusion in a patient with acoustic neuroma by brain SPECT with^99mTc HMPAO. A high spatial resolution SPECT system with three detectors equipped with fan-beam collimators was employed. This is the first report of a defect in the brainstem being visualized by perfusion SPECT and this method could make it possible to clarify the cause of a remote effect on the cerebellar perfusion by injury to the brainstem.     

Airborne contamination in an operating suite: report of a five-year survey.

Airborne contamination in an operating suite was studied with a slit sampler, settle plates and a light-scattering particle counter. In conventional operating rooms there was a significant difference between the empty rooms and rooms in use; the mean total bacterial count by a slit sampler changed from 1.1 in empty to 42.5 c.f.u./m3 in use (39 times increase), the settle plates count changed from 1.5 to 17.4 c.f.u./m2/min (12 times increase), and the mean total particle count changed from 56.9 to 546.7/l (10 times increase) respectively. The increase was caused mainly by persons present in the room. Another difference was found between zones in the operating suite; the bacterial count in the clean area doubled in the semi-clean area and further doubled in the dirty area in slit sampler count as well as settle plates count, and particle count in the clean area increased by 14 times in the semi-clean and dirty areas. This difference resulted from the different quality of the ventilating system. Air cleanliness of operating rooms in use by persons present in the room dropped to a level between the clean and the semi-clean area in spite of the high quality of the ventilating system. Bacterial species identified were mostly coagulase negative staphylococci and micrococci. Our study indicates that reduction of airborne contamination in an operating suite is accomplished by the combination of an efficient ventilating system and the restriction of the number of persons present in the room.