(1) While several factors correlated with cisplatin nephrotoxicity, most of the observed nephrotoxicity was not explained by the variables identified. (2) While most patients received intravenous hydration, patients receiving high hydration volumes did not have significantly less nephrotoxicity than patients receiving lower hydration volumes: (3) Of the variables identified, serum albumin, metoclopramide and phenytoin may have affected nephrotoxicity by altering cisplatin uptake into or distribution within the kidney.
Autopsy tissues were obtained from 30 patients who had received cisplatin antemortem; the tissues were assayed for platinum by flameless atomic absorption spectrometry. Patients with antemortem evidence of renal toxicity had higher renal cortical platinum concentrations than did patients without evidence of kidney damage. In addition, patients with nephrotoxicity were more likely than patients without toxicity to have renal cortical platinum concentrations that were higher than renal medullary platinum concentrations. Overall, the two variables most closely associated with an increase in serum creatinine with treatment were renal cortical platinum concentration (P less than .02) and cumulative dose of cisplatin (P less than .05). These two variables were important independently of one another. Renal cortex platinum concentrations correlated inversely with time from last treatment until death, whereas hepatic platinum concentrations did not. In contrast, hepatic platinum concentrations correlated with dose of cisplatin while renal platinum concentrations did not. Our results suggest the following: (1) cisplatin-induced renal toxicity is tissue-platinum-concentration dependent and cisplatin-dose dependent; and (2) cisplatin may be handled differently at the molecular level in liver and kidney.
SY N 0 PSISThe transmission infrared spectra of exfoliated endocervical mucin-producing columnar epithelial cells and the attenuated total reflectance ( ATR) infrared spectra of the singlecolumnar cell layer on the endocervical tissues have been measured and compared with the corresponding infrared spectra of the ectocervical squamous cells and squamous epithelium. The infrared spectra of the exfoliated cervical cells obtained from the present work are comparable with those directly measured from the epithelia on the cervical tissues by ATR technique. The transmission infrared spectra of endocervical columnar epithelial tissue containing some components of the underlying connective tissue have also been measured and compared with the ATR/FTIR ( Fourier-transform infrared) spectra of the endocervical columnar epithelial tissue. The effects of the contaminated connective tissue on the infrared spectra of the endocervical columnar epithelial tissue have demonstrated that ATR/FTIR is a more desirable method than the transmission method to obtain meaningful and good-quality infrared spectra of tissue samples, especially samples consisting of thin layers of different types of tissues. Substantial differences in the infrared spectra between the columnar cells and squamous cells on the endocervical and ectocervical tissues, respectively, were evident. The strong glycogen bands in the infrared spectrum of the ectocervical squamous cells are absent in the spectrum of the endocervical columnar cells. This spectral change is similar to that observed in malignant squamous cells. Therefore, if the decrease in the intensity of the glycogen bands is used as the only criterion for the determination of cellular abnormalities in the cervix, the presence of a large number of normal endocervical columnar cells in the cervical specimen would lead to a false result. Consequently, in addition to the glycogen bands, other features in the infrared spectra should be considered for the evaluation of abnormalities in exfoliated cervical epithelial cells. In order to identify the spectral features that are unique to endocervical columnar cells, the infrared spectra of an aqueous solution of glycogen, the mucus from the endocervix, and the connective tissues from both the endocervix and the ectocervix have also been measured and analyzed. lignant human squamous epithelial tissues, the exfoliated epithelial cells from human tissues, as well as the cultured malignant cells have been investigated systematically in Our Extremely-high-quality infrared spectra of these samples have been obtained. In the study of cervical tissues and cells, we found that many features in the infrared spectra of the cervical specimens with cancer, precancerous lesions ( dysplasia ) , and in-
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