Biomedical subjects

Gary R Stevens

Publications and source records attributed to Gary R Stevens.

8 recordsLinked to original sources

PubMed2006

Opening plugged tympanostomy tubes: effect of biofilm formation.

OBJECTIVE: To determine if the presence of a bacterial biofilm impacts the rate of clearing of mucoid plugs from tympanostomy tubes (TTs). STUDY DESIGN AND SETTING: Ex vivo model. Stainless steel Reuter Bobbin TTs (n = 18) were placed in growth medium with Pseudomonas aeruginosa and Streptococcus pneumoniae for 12 days to promote biofilm formation. Tympanostomy tubes (n = 18) placed in growth medium, without bacteria, for 12 days served as controls. Biofilm formation was assessed by scanning electron microscopy. All TTs were filled with middle ear mucus and allowed to dry, thereby forming a plug. TTs were placed in a model ear chamber, covered with ofloxacin otic solution, and the time to clear each plug was recorded. RESULTS: Biofilm formation was consistently encountered on TTs exposed to bacteria but in no TTs in the control group. There was a significant effect of the biofilm on plug clearance, favoring TTs without a biofilm (P = 0.0333). Although there was no significant difference in the proportion of unplugged TTs (P = 0.264), TTs with a biofilm did not clear plugs as rapidly as TTs without a biofilm (P = 0.0416). CONCLUSIONS: The presence of a biofilm may slow the time to clear mucoid TT plugs, but it does not seem to affect the overall proportion of TTs that are unplugged.

Anti-Bacterial Agents↗

PubMed2005

Opening plugged tympanostomy tubes: effect of inner diameter and shaft length.

OBJECTIVE: To determine whether tympanostomy tube (TT) inner diameter or shaft length impacts the rate of mucoid plug clearance. STUDY DESIGN AND SETTING: Ex vivo model. Silicone TTs with different inner-diameters (ID) and shaft-length (SL) pairings (1.14 mm ID x 12 mm SL versus 1.14 mm ID x 1 mm SL; 1.14 mm ID x 4.8 mm SL versus 1.32 mm ID x 4.8 mm SL) were plugged with middle-ear mucus (n = 15 per group) and placed in a model ear chamber. Ofloxacin otic solution was instilled into the chamber to cover the plugged TT, and the time to clearance of each plug was recorded. RESULTS: TTs with larger IDs ( P = 0.019) and greater SLs ( P = 0.033) cleared plugs more rapidly. However, the difference in the percentage of tubes that unplugged was not significant ( P = 0.151). CONCLUSIONS: Rate of ex vivo TT plug clearance may be altered by changing TT ID and SL.

Anti-Bacterial Agents↗

PubMed2005

Preoperative antibiotic and steroid therapy and hearing loss caused by semicircular canal transection in pseudomonas otitis media.

OBJECTIVE: The purpose of this experiment was to determine whether preoperative administration of antibiotics and corticosteroids can attenuate the severity of hearing loss (HL) with semicircular canal (SC) transection in a guinea pig model of Pseudomonas aeruginosa (PA) otitis media (OM). Study design and setting Prospective and controlled. METHODS: OM was induced in 64 pigmented guinea pigs by bilateral, transtympanic injection of PA. Two to 4 days later, 1 horizontal SC was randomly transected. In the 1st series, antibiotic therapy was initiated either immediately before or after surgery. In the 2nd series, all animals received preoperative antibiotics, and half received dexamethasone before surgery. Hearing was tested before and after surgery. RESULTS: PA was recovered in all ears. SC transection was associated with significant HL. HL was better in animals given antibiotics preoperatively (clicks, 16 versus 32 dB, P = 0.0220). Addition of preoperative steroids did not significantly further reduce HL (7 versus 14 dB for clicks, P = 0.6919). CONCLUSIONS: HL caused by SC transection in PA OM may be attenuated with preoperative antibiotic therapy in the guinea pig.

Animals↗

PubMed2004

Androgen ablation therapy for prostate carcinoma suppresses the immunoreactive telomerase subunit hTERT.

BACKGROUND: Telomerase is a ribonucleoprotein complex that protects the ends of chromosomes from degradation. Its catalytic subunit, hTERT, controls its activity. Prior data in prostate carcinoma cases indicated that immunohistochemical hTERT reactivity increases with tumor grade and may be absent in lower grade cases. The effect of complete androgen ablation (CAA) on tumor hTERT expression was uncertain. METHODS: hTERT immunostaining was performed on the cancerous pretreatment biopsy tissue of 30 men who consecutively underwent CAA with bicalutamide and goserelin acetate for 30 days prior to undergoing radical prostatectomy, and on their tumor tissue from radical prostatectomy. As controls, biopsy and prostatectomy samples from 30 untreated men were studied. Nuclear staining was evaluated by two observers, and the change in staining between biopsy and prostatectomy samples was evaluated using the Student t test in both groups. RESULTS: The percent of reactive tumor nuclei in treated men declined from 36.7% to 13.2% (P = 0.0001), and declined from 19.8% to 16.1% in untreated men (P = 0.4). The greater mean hTERT reactivity in the treated men's biopsy specimens was attributed to an increased proportion of higher (Gleason score > or = 7) grade tumors. The decline in hTERT immunostaining remained significant after normalizing it to that of the untreated group (P = 0.002). The original Gleason scores, corresponding declines in the percentage of reactive tumor nuclei, and significance were: Gleason score < or = 6: 11% (P = 0.03); Gleason score of 7: 23% (P < 0.006); and Gleason score > or = 8: 46% (P < 0.005) (from a mean 63% to 17%). CONCLUSIONS: CAA for prostate carcinoma can be considered an antitelomerase therapy. The steepest reduction in telomerase activity was noted in the highest grade tumors.

Aged↗

PubMed2004

Pharmacokinetics and safety of the MRI contrast agent gadoversetamide injection (OptiMARK) in healthy pediatric subjects.

RATIONALE AND OBJECTIVE: This clinical trial examined the pharmacokinetics of gadoversetamide, a magnetic resonance imaging contrast agent, in normal pediatric subjects. MATERIALS AND METHODS: Seventeen healthy pediatric subjects received a single intravenous injection of gadoversetamide (0.1 mmol/kg, 0.2 mL/kg). Sixteen subjects that were evaluable for pharmacokinetic analysis fell into 2 stratified age groups: 2 years to <5 years and 5 years to <18 years of age. Serum samples were analyzed for total gadolinium as a measure of gadoversetamide concentration. RESULTS: Statistical analysis demonstrated significant (P < 0.05) age-related trends in the mean elimination half-life (t 1/2) of gadolinium with the older group having a slightly longer t 1/2 (1.39 hours) than the younger group (1.19 hours). No age-related changes occurred in volume of distribution or total body clearance, when normalized to body weight or body surface area. CONCLUSIONS: Based on this preliminary pharmacokinetic assessment, no adjustment from the approved adult gadoversetamide dose of 0.1 mmol/kg should be necessary for children aged 2 or older.

Adolescent↗

PubMed2003

Opening plugged tympanostomy tubes: effect of tube composition.

OBJECTIVE: We sought to determine if tympanostomy tube (TT) composition impacts the rate of clearing mucoid plugs. DESIGN: The study used an ex vivo model. METHODS: TTs with a standard shaft length and inner diameter, varying only by composition materials, were studied. Thirty TTs of each biomaterial (stainless steel, titanium, silicone, fluoroplastic, ion-bombarded silicone, and phosphorylcholine-coated fluoroplastic) were plugged with middle-ear mucus and placed in a model ear chamber. Ofloxacin otic solution was instilled into the chamber to cover the plugged TT. Time to clear each plug was recorded. RESULTS: Ion-bombarded silicone TTs cleared more rapidly than plain silicone TTs (P = 0.0042), but no other statistically significant difference among TT materials was observed. CONCLUSIONS: TT composition does not significantly affect the rate or "ease" with which TTs may be opened after they become plugged with mucus ex vivo. The higher rate of plug clearance observed with ion-bombarded silicone relative to untreated silicone suggests that improvements may be possible with alterations in either TT composition or surface preparations.

Biocompatible Materials↗

PubMed2003

Evaluation of various compounds to inhibit activity of matrix metalloproteinases in the tear film of horses with ulcerative keratitis.

OBJECTIVE: To examine in vitro effects of various antiproteolytic compounds on activity of matrix metalloproteinase (MMP)-2 and -9 in the tear film of horses with active corneal ulcers. SAMPLE POPULATION: Samples of tear film obtained from the eyes of 34 horses with active ulcerative keratitis. PROCEDURE: Horses were sedated, and tear samples were collected from the lower fornix of 34 ulcerated eyes by use of capillary tubes. The protease inhibitors 0.2% EDTA, 0.1% doxycycline, 10% N-acetylcysteine (NAC), 0.1% solution of a modified dipeptide that contains hydroxamic acid (ie, ilomostat), 0.1% alpha1-proteinase inhibitor (PI), 0.5% alpha1-PI, and 100% fresh equine serum (ES) were used to treat pooled samples. Amount of latent and active MMP-2 and -9 was measured by optical density scanning of gelatin zymograms of treated and untreated tear samples. RESULTS: Pooled tear samples obtained from ulcerated eyes contained the latent and active forms of MMP-2 and -9. Compared with MMP activity in untreated samples, total MMP activity (sum of all bands detected) observed on the gelatin zymogram gels was reduced by 99.4% by EDTA, 96.3% by doxycycline, 98.8% by NAC, 98.9% by ilomostat, 52.4% by 0.1% alpha1-PI, 93.6% by 0.5% alpha1-PI, and 90.0% by ES. CONCLUSIONS AND CLINICAL RELEVANCE: We documented that EDTA, doxycycline, NAC, ilomostat, alpha1PI, and ES inhibited MMP activity in vitro. Because these compounds use different mechanisms to inhibit various families of proteases in the tear film of horses, a combination of these protease inhibitors may be beneficial for treatment of corneal ulcers in horses.

Acetylcysteine↗

PubMed2002

The OptiMARK clinical development program: summary of safety data.

PURPOSE: To describe and summarize the safety data from the OptiMARK clinical development program. MATERIALS AND METHODS: In the 18 clinical studies comprising the clinical program, doses ranging from 0.1 to 0.7 mmol/kg were administered to healthy adult volunteers, patients with hepatic or renal impairment, and patients with confirmed or highly suspected central nervous system (CNS), liver, breast, vascular, bone, or soft tissue pathologies. A total of 2038 injections of OptiMARK, Magnevist, or placebo were administered to 1684 subjects. Safety assessments were performed at appropriate intervals during all Phase 1, 2, and 3 studies. RESULTS: Of the 1684 subjects exposed to a study drug or placebo in the clinical development program, 646 subjects experienced 1293 adverse events. Thirty-one percent of the OptiMARK injections were associated with an adverse event. In comparison, 35% of Magnevist injections and 48% of placebo injections were associated with at least one adverse event. CONCLUSIONS: OptiMARK was safe and well-tolerated with a safety profile similar to that of Magnevist.

Adult↗