BACKGROUND The purpose of this study was to analyze the extent of hypoxia in prostate carcinoma tumors using the Eppendorf pO2 microelectrode and correlate this with pretreatment characteristics and prognostic factors. METHODS Custom‐made Eppendorf pO2 microelectrodes were used to obtain pO2 measurements from the pathologically involved region of the prostate (as determined by the pretreatment sextant biopsies) as well as from a region of normal muscle for comparison. Each set of measurements comprised approximately 100 separate readings of pO2, for a total of 10,804 individual measurements. Fifty‐five patients with localized prostate carcinoma were studied: Forty‐one patients received brachytherapy implants, and 14 patients underwent radical prostatectomy. The pO2 measurements were obtained in the operating room by using a sterile technique under spinal anesthesia for the brachytherapy group and under general anesthesia for the surgery group. The Eppendorf histograms were recorded and described by the median pO2, mean pO2, and percentage < 5 mm Hg and < 10 mm Hg. A multivariate mixed‐effects analysis for the prediction of tumor oxygenation was performed and included the following covariates: type of tissue (prostate vs. muscle), type of treatment (implant vs. surgery) and/or anesthesia (spinal vs. general), prostate specific antigen level, disease stage, patient age and race, tumor grade, tumor volume, perineural invasion, and hormonal therapy. RESULTS Due to differences in patient characteristics and the anesthesia employed, control measurements were obtained from normal muscle (in all but two patients). This internal comparison showed that the oxygen measurements from the pathologically involved portion of the prostate were significantly lower (average median pO2, 9.9 mm Hg) compared with the measurements normal muscle (average median pO2, 28.6 mm Hg; P < 0.0001). A multivariate, linear, mixed analysis demonstrated that, among all of the patients, the significant predictors of oxygenation were tissue (prostate vs. muscle) and anesthesia (spinal vs. general) or treatment (implant vs. surgery). Among the brachytherapy (spinal anesthesia) patients, the significant predictors of pO2 were tissue type, disease stage, and patient age. There were no significant predictors of oxygenation in the surgical (general anesthesia) group. CONCLUSIONS This study, employing in vivo electrode oxygen measurements, demonstrated that hypoxia exists in prostate carcinoma tumors. A dramatic effect of anesthesia was observed, likely due to modulation of polarography in the presence of fluorine. Within the group of brachytherapy (spinal anesthesia) patients, increasing levels of hypoxia (within prostatic tissue) correlated significantly with increasing clinical stage and patient age. More patients will be accrued to this prospective study to further correlate the oxygenation status in prostate carcinoma tumors with known prognostic factors and, ultimately, treatment outcome. Cancer 2000;89:2018–24. © 2000 American Cancer Society.
Activation of the transcriptase in purified reovirus by chymotrypsin requires facilitating conditions in the digestion mix. In the presence of facilitation the virions are uncoated to cores. Without facilitation, uncoating is blocked at an intermediate stage, with transcriptase latent. Two independent types of facilitation have been discovered. The first type is mediated by K+, Rb+ or Cs+ ions. A second type, described here, is mediated by suitably high concentrations of virus in the digestion mix and requires collisions between intermediate subviral particles for its occurrence. The virus-concentration-mediated process is reversibly inhibited by high levels of active chymotrypsin.
RO-07-0582 toxicity studies were performed in 12 patients for a total of 16 assays. Single and multifraction dose schedules were used, and drug concentrations in solid tumor tissue, cerebrospinal fluid, and blood (at 14 to 24 hr.) were established. A severe peripheral neuropathy occurred in 1 patient on the multifraction regimen when the total dosage reached 24 g. Drug absorption and concentration in the blood do not significantly differ from that of metronidazole. Maximum blood levels were reached at from 2 to 4 hr., and several days subsequent to administration had stabilized to levels only slightly above control levels.
The effects of sham ovariectomy (SOVX) or ovariectomy (OVX) on (1) basal luteinizing hormone (LH) concentrations, (2) number of LH peaks per hour and (3) magnitude of LH peaks were determined in prepubertal and pubertal beef heifers. Basal LH concentrations were not influenced by SOVX of prepubertal or pubertal heifers. However, after OVX, basal LH concentrations increased between 168 and 192 hr in prepubertal heifers and between 72 and 80 hr in pubertal heifers. The number of LH peaks per hour was not influenced by SOVX but OVX caused an increase in the number in both prepubertal and pubertal heifers, and the increase occurred sooner after OVX in pubertal than in prepubertal heifers. The magnitude of LH peaks was similar for both prepubertal and pubertal heifers prior to SOVX and OVX. Magnitude of LH peaks was unchanged after SOVX in prepubertal and pubertal heifers, but increased within the first 24 hr after OVX in pubertal heifers and within 168 to 192 hr after OVX in prepubertal heifers. These data indicate that inhibition of LH secretion by ovaries occurred in both prepubertal and pubertal beef heifers. The time-related differences between prepubertal and pubertal heifers in basal LH concentrations, number of LH peaks per hour and magnitude of the LH peaks after OVX may reflect a difference in endocrine environment in these two reproductive states. However, this hypothesis was not tested in this experiment.
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