PubMed HealthSearch

Biomedical subjects

C Sheridan

Publications and source records attributed to C Sheridan.

At least 19 recordsLinked to original sources

Non-vascular vitreoretinopathy: the cells and the cellular basis of contraction.

BACKGROUND: We consider epiretinal membrane in terms of the two repair processes of gliosis and fibrosis and look at the cellular basis of contraction. METHODS: Pathological material removed at surgery was examined by a range of morphological procedures. Cultures of fibroblasts, retinal pigment epithelium cells and retinal glia were subjected to bioassays which relate to behavioural activities in scar formation. RESULTS AND CONCLUSIONS: Our findings highlight the importance of activities such as migration and adhesion in the formation of epiretinal membranes, and also show that these activities are central to our understanding of contraction.

Animals

'En bloc' dissection of epimacular membranes using aspiration delamination.

'En bloc' dissection is a technique in which epiretinal membranes (ERM) are separated from the retina as a single lamina with a 20-gauge blunt flute needle. We used this technique to remove epimacular membranes of various aetiologies in a consecutive series of 25 eyes, with a minimum follow-up of 5 months (mean 10.4 months). Small residual epicentres of ERM away from the fovea remained in 7 (29.1%) eyes only; 3 were inside and 4 outside the temporal vascular arcades. Postoperatively 64% (16/25) of patients achieved a final visual acuity of 6/12 or better and 76% (19/25) achieved a final visual acuity of 6/18 or better. Progressive lens opacities were the most important postoperative complication in phakic eyes that significantly affected the visual results. This technique successfully removed epimacular membranes over a wide area, without the need to find a starting edge or the use of sharp instruments near the retina. Diaphanous ERMs with ill-defined borders and tenaciously adherent membranes could be removed with minimal trauma to the underlying retina. Histopathological and immunohistochemical examination of 10 ERMs demonstrated the absence of internal limiting lamina in 6 (60%).

Adolescent

Comparison of two cochlear implant speech processors in better versus poorer performers.

The performance and subjective preferences for two different speech-processing strategies, the Speak strategy in the Cochlear Spectra 22 speech processor and the Multipeak (Mpeak) strategy in the Mini Speech Processor (MSP), are compared within two adult patient groups. Ten experienced cochlear implant (CI) users were selected for this study. One group of 5 CI users have significant open-set speech recognition, and the second group consisted of experienced CI users who have little or no open-set speech recognition on standardized tests (< 30% on sentence tests; < 10% on monosyllabic word tests). While only 4 of the 5 users in each group were available to complete this evaluation, suitable comparisons on the Speak and Mpeak strategies on test performance were possible within each patient group. The performance tests were necessarily different to suit each patient group; however, general trends of test scores and subjective evaluations of each speech processor are compared between these two groups. While the performance scores and subjective ratings consistently favored the Speak strategy in the first group of users, with good open-set speech recognition, the results within the second group were more variable. These findings have significant implications for individual patient and processor selection.

Cochlear Implants

Phase I trial of intravenous and intraperitoneal administration of granulocyte-macrophage colony-stimulating factor.

To assess the toxicity, pharmacokinetics, and local and systemic effects of the intraperitoneal (i.p.) administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) at various dosages, 13 patients with predominantly i.p. malignancies refractory to standard chemotherapy were studied. GM-CSF was administered intravenously (i.v.) for 5 consecutive days; 21 days later the same dosage of GM-CSF was administered i.p. for 5 consecutive days. Four dosage levels were studied: 1, 2, 4, and 8 micrograms/kg/day. GM-CSF was well tolerated after i.v. and i.p. administration at doses up to 8 micrograms/kg/day. A transient fall followed by an elevation of circulating white cells was observed over a 24-h period after both i.v. and i.p. GM-CSF administration (mean minimum +/- SE as % baseline): 38 +/- 8% at 30 min after i.v. administration, 21 +/- 5% at 60 min after i.p. administration; mean maximum: 220 +/- 41% at 6 h after i.v. administration, 202 +/- 39% at 12 h after i.p. administration). The magnitude and time course of these changes were very similar for the two routes despite an up to 400-fold difference in serum GM-CSF levels at the same time points. Changes in leukocyte count and differential and neutrophil function were also similar over the 3-week period after both i.v. and i.p. administration. In the only patient who had i.p. GM-CSF levels assayed, i.p. administration achieved high levels of GM-CSF in peritoneal fluid (Cmax 343 ng/ml) with maintenance of high concentrations over 24 h (C24h 128 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The development of a test of speech reception disability for use in 5- to 8-year-old children with otitis media with effusion.

The study aims to develop a test of speech reception disability under simulated classroom conditions for use in young (5-8 year old) schoolchildren, to manage children with otitis media with effusion more effectively. A new video test, TADAST (Two Alternative Auditory Disability and Speech Reception Test), has been constructed in stages by extensively modifying the FADAST (Four Alternative) currently used to assess auditory disability in adults. Minimal word pair lists which were easily identifiable in picture form were developed and refined, and then formulated as a two alternative forced choice picture test. The distribution characteristics of the new test were defined in 89 schoolchildren with and without otitis media with effusion (OME) and compared with pure-tone audiometry performed at the same time. The test correlated highly with audiometry in older children. The distribution characteristics revealed a considerable proportion of children with bilateral OME with little functional disability who might otherwise be at risk of surgery. The test appeared to be sensitive to a 'history of OME' effect. Further refinements are needed to develop a final version which could also be used to evaluate hearing disability in 4-year-old children.

Audiometry, Pure-Tone

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