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Biomedical subjects

C Sheridan

Publications and source records attributed to C Sheridan.

32 records · Page 2Linked to original sources

In search of missing links in otology. III. Development of a new animal model for cholesteatoma.

An experimental study was conducted in chinchillas regarding the pathogenesis of acquired cholesteatoma (keratoma). The placement of a chemically modified gelatin membrane from the external auditory canal to the promontory through a tympanic membrane perforation stimulated squamous epithelial cell migration. Cholesteatoma formation with the presence of keratin debris and inflammatory reactions was observed in the middle ear and anterior bulla in 53.5% of the experimental animals. These experimental findings show for the first time the presence of epithelial migration and true cholesteatoma formation in the middle ear of chinchillas in an experimental model with deliberate perforation of the tympanic membrane. Erosion of the cochlear walls was observed in areas with granulation tissue and cholesteatoma. The importance and significance of the migration of squamous epithelium and of the middle ear inflammatory reaction in the genesis of acquired cholesteatomas are discussed.

Animals↗

A phase I trial of recombinant human interleukin-1 beta alone and in combination with myelosuppressive doses of 5-fluorouracil in patients with gastrointestinal cancer.

We studied escalating doses of recombinant human interleukin-1 beta (IL-1 beta) alone and after a myelosuppressive dose of 5-fluorouracil (5-FU) in patients with gastrointestinal cancer. Transient neutropenia, monocytopenia, and lymphocytopenia were observed followed by a 1.3- to 6.0-fold (mean, 3.46-fold) dose-dependent neutrophil leukocytosis (P less than .00001) on the days of IL-1 beta administration. Increases in platelet counts were observed at a median of 14 days (range, 6 to 23) after IL-1 beta administration. Transient hypoglycemia, rebound hyperglycemia, elevations in serum cortisol, and C-reactive protein were observed. Side effects included fever, rigors, and headache in the majority of patients. Hypotension was observed in three of five patients at the highest dose level (0.1 micrograms/kg) and was dose-limiting. Fewer days of neutropenia were noted after 5-FU plus IL-1 beta than after 5-FU alone; however, this difference did not reach statistical significance. These data show that IL-1 beta has stimulatory effects in human hematopoiesis.

Adult↗

In vivo measurements of bone marrow cellularity using volume-localized proton NMR spectroscopy.

Volume-localized proton NMR spectroscopy was used to estimate bone marrow cellularity in the posterior iliac crests of patients undergoing treatment with hematopoietic growth factors for a variety of hematologic and neoplastic disorders. Twelve patients were accrued, six of whom were studied more than once, yielding a total of 25 measurements. These data were compared to cellularity assessments derived from conventional bone marrow core biopsies obtained within a 24-h period before or after the NMR exam. The results obtained by the two methods are well correlated (R = 0.94, P less than 0.001), suggesting that this noninvasive technique may preclude the need for biopsies in some cases.

Adult↗

CA 125 levels in patients with ovarian carcinoma undergoing autologous bone marrow transplantation.

Levels of CA 125, determined in three patients with ovarian carcinoma undergoing autologous bone marrow transplantation, dropped significantly in the month after bone marrow transplantation. This decrease was linear by multiple regression analysis. The CA 125 decrease after bone marrow transplantation in patients with nonevaluable or stable disease may represent biologic response to high-dose therapy.

Adult↗

Ototoxicity of cisplatin vs. platinum analogs CBDCA (JM-8) and CHIP (JM-9).

Cis-diamminedichloroplatinum (cisplatin), a divalent platinum compound and cell-cycle nonspecific chemotherapeutic agent, produces a permanent high-frequency sensorineural hearing loss and a dose-related cumulative renal insufficiency with tubular necrosis and interstitial nephritis. Synthetic platinum analogs are presently being tested to identify an analog with greater antitumor activity, but less ototoxicity and nephrotoxicity than cisplatin. The objectives of this study were to analyze the potential cochlear and nephrotoxic effects of two synthetic platinum analogs presently in phases I and II of clinical trials, CBDCA [JM-8 or cis-diammine, 1,1-cyclobutane dicarboxylato (2)-0,0(1)-platinum (NSC-241240)] and CHIP [JM-9 or cis-dichloro-trans-dihydroxybisisopropylamine platinum IV (NSC-256927)]. Cytocochleography, auditory brain-stem evoked response (ABR), double-blind light microscopy of renal tissues, and gamma emission analysis of 195mpt localization in viscera and inner ear were employed in the evaluation of cisplatin and platinum analogs (JM-8 and JM-9) in adult guinea pigs. Final results indicate that the investigational chemotherapeutic analogs CBDCA (JM-8) and CHIP (JM-9) do not produce the ototoxicity and nephrotoxicity characteristic of cisplatin. Furthermore, these findings demonstrate 195mpt localization in the vestibular labyrinth and confirm previous platinum distribution studies in the organ of Corti and stria vascularis tissues.

Animals↗

Vestibular morphological analysis of the effects of cisplatin vs. platinum analogs, CBDCA (JM-8) and CHIP (JM-9).

Synthetic second generation chemotherapeutic platinum analogs are presently being tested to identify an analog with greater antitumor activity, but less ototoxicity and nephrotoxicity than cisplatin. The objective of this study was to analyze potential vestibular effects of cisplatin and of the two platinum analogs, CBDCA (cis-diammine 1,1-cyclobutane dicarboxylato [2]-0,0(1) platinum or JM-8) and CHIP (cis-dichlorotrans-dihydroxy-bis(isopropylamine) platinum [IV] or JM-9) using scanning and transmission electron microscopy of vestibular neuroepithelium from the albino guinea pig. Vestibular neuroepithelial damage was not demonstrated in either cisplatin- or the analog-treated animals when administered at equitoxic doses.

Animals↗