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Biomedical subjects

N D Schwade

Publications and source records attributed to N D Schwade.

10 recordsLinked to original sources

In vitro study of drug-loaded bioresorbable films and support structures.

Bioresorbable films can serve simultaneously as anatomic support structures and as drug delivery platforms. In the present study, bioresorbable poly(L-lactic acid) (PLLA) films containing dexamethasone were prepared by solution processing methods. Their in vitro studies focused on the mechanical properties with respect to morphology and degradation and erosion processes. Novel expandable support devices (stents) developed from these films were studied. Such a stent would support conduits, such as the neonatal trachea to treat tracheal malacia, until the airway matures, and would then be totally resorbed, obviating the need for a removal operation. The PLLA films showed good initial mechanical properties. They can accommodate drug incorporation on the film surface and also in the bulk. Water incubation of the films results in a decrease in their tensile mechanical properties, due to chain scission and morphological changes. These changes can vary from degradation and small changes in morphological features to erosion, leading to a microporous structure, depending on the polymer. The cumulative release of dexamethasone from the films is linear. The rate of release is determined by the film's structure (drug location/dispersion). The stents demonstrated good mechanical properties. The initial radial compression strength of the stent is determined mainly by the polymer structure. Drug incorporation has a minor effect on the initial stent strength. Exposure to radial compression stress results in elastic reversible deformation or a sudden brittle fracture, depending on the polymer. A 20-week in vitro study of the stents showed that they are applicable for supporting body conduits, such as the trachea.

Absorbable Implants↗

Particulate dermal matrix as an injectable soft tissue replacement material.

Products currently used as injectable soft tissue replacement materials in the dermatologic, plastic and reconstructive, and urological fields exhibit several shortfalls including reactivity, migration, rapid degradation, and necessity of a donor site. This study examines the feasibility of providing a particulate acellular human dermal matrix for injection as a soft tissue replacement material that addresses many of these issues. Animal feasibility studies tested differences in implant performance related to processing techniques, matrix concentration, and volume of the collagen matrix to be injected. Results demonstrated that processing techniques that involve shearing and tearing of the dermal collagen matrix resulted in frayed and damaged collagen bundles and led to rapid resorption or loss of the implant, when injected subcutaneously in a rat model. Processing the collagen matrix in liquid nitrogen resulted in less damage to the collagen matrix and exhibited longer persistence, when compared to the damaged collagen matrix. This particulate matrix also exhibits rapid repopulation by host cells that should enhance revascularization and remodeling. The particulate nature of this processed dermal matrix allows for easy delivery of concentrations up to 330 mg/mL, which exceeds that of other currently used products. This increased concentration should allow for decreased need of "overcorrection" and repeated injections.

Animals↗

Characteristics of bony erosion in allergic fungal rhinosinusitis.

OBJECTIVES: Erosion of bone with or without extension of disease into adjacent anatomic spaces is observed among some patients with allergic fungal rhinosinusitis (AFRS). The objective of this report is to further define these findings as they relate to this disease. STUDY DESIGN: Retrospective chart review of 142 patients with AFRS diagnosed using the Bent-Kuhn criteria. All patients were treated at a single institution. RESULTS: Approximately 20% of patients with AFRS demonstrated bone erosion on CT scan. The ethmoid sinus was the most commonly eroded site. The orbit and anterior cranial fossa were the most common adjacent anatomic spaces to exhibit disease extension. Sinus expansion, not the specific organism identified, was associated with the presence of bone erosion. Surgical management with endoscopic techniques was successful for all patients without any major perioperative complications. CONCLUSION: Bone erosion can be related to AFR. Recognition of this possibility is important because bone erosion can be interpreted as an indication of invasive pathosis. In the presence of bone erosion or disease extension, endoscopic techniques can be used to surgically manage this disease.

Bone Resorption↗

Use of immunotherapy in previously treated patients with allergic fungal sinusitis.

OBJECTIVE: Sixty patients with a diagnosis of allergic fungal sinusitis were studied. The objective was to show whether, after initial surgical removal of allergic mucin and polyps, immunotherapy decreases re-operation rates and office visits that require medical intervention. STUDY DESIGN AND SETTING: Sixty patients with adequate follow-up for at least 1 year were evaluated: 24 patients who did not receive immunotherapy and 36 patients whose treatment included postoperative immunotherapy. RESULTS: The re-operation rates were 33.0% in those not receiving immunotherapy versus 11.1% in the treated group. Furthermore, the total number of postoperative office visits that required medical therapy decreased from 4.79 per patient to 3.17 with the addition of immunotherapy. CONCLUSION/SIGNIFICANCE: These results indicate that immunotherapy is a beneficial part of the overall treatment regimen for allergic fungal sinusitis.

Adolescent↗

Structured drug-loaded bioresorbable films for support structures.

Bioresorbable films can serve simultaneously as anatomic support structures and as drug delivery platforms. In the present study, bioresorbable PLLA films containing dexamethasone were developed through solution processing. The effect of processing parameters on the film morphology and the resulting mechanical properties was studied. A model describing the structuring of these films is suggested. Generally, the solvent evaporation rate determines the kinetics of drug and polymer crystallization and thus, both the mode of drug dispersion in the polymer and the resulting mechanical properties. Two types of structured films were studied: (1) a polymer film with drug located on its surface, obtained due to drug skin formation accompanied by a later polymer core formation; and (2) a polymer film with small drug particles and crystals distributed within the bulk, obtained by parallel solidification of the two components. A prototypical application of these films is an expandable biodegradable support structure (stent). which we have developed. This stent demonstrated good initial mechanical properties. The film structure has only a minor effect on the stent radial compression strength, but more significantly affects the tensile mechanical properties.

Biocompatible Materials↗

Fosfomycin does not inhibit the tumoricidal efficacy of cisplatinum.

OBJECTIVES: This study investigates the effect of fosfomycin on the tumoricidal efficacy of cisplatinum. STUDY DESIGN: Prospective study utilizing the FaDu squamous cell carcinoma cell line and a nude mouse tumor xenograft model. METHODS: Tumor cell growth was assessed in vitro in the presence of cisplatinum and/or fosfomycin utilizing the MTT assay. An optimal cisplatinum dose and dosing schedule was established in a nude mouse tumor xenograft model of squamous cell carcinoma. Using this model, fosfomycin was tested at three dosages and tumor growth monitored over 4 weeks. RESULTS: Mice treated with cisplatinum and fosfomycin had smaller tumors than those treated with cisplatinum alone (P<.01). CONCLUSIONS: This study is the first demonstration that fosfomycin does not inhibit the tumoricidal efficacy of cisplatinum in vivo. This suggests that fosfomycin may be useful in preventing cisplatinum-induced ototoxicity and nephrotoxicity in humans without altering the tumor response rate.

Animals↗

Salt-load electrocochleography.

OBJECTIVE: To introduce a new protocol for diagnostic electrocochleography using a pretest oral salt load to improve test sensitivity in patients with suspected inner ear fluid imbalance. STUDY DESIGN: A retrospective review of patients who reported vertigo that, by medical history, was suggestive of an inner ear fluid imbalance was preformed. The patients received a complete audiovestibular evaluation that included a baseline electrocochleogram. Despite the incapacitating nature of their vertigo, there were no symptoms or electrophysiologic abnormalities that would isolate an etiologic ear. After the baseline studies, the patients received 4 g of sodium chloride daily for 3 days before repeat electrocochleography. A control group of 13 healthy volunteers with normal baseline electrocochleography and pure tone audiometry was tested under similar conditions. SETTING: This study was conducted at an ambulatory care clinic associated with a tertiary referral medical center. INTERVENTION: Electrocochleography was performed using alternating polarity clicks presented at a rate of 9.7/sec at 95 dB nHL by an extratympanic TIPtrode electrode and recorded with a Nicolet Spirit (Nicolet Instrument Corp., Madison, WI, U.S.A.). Responses were averaged for 1000 sweeps using a 10-msec time base with bandpass filtering from 5 to 1500 Hz. A summating potential/action potential (SP/AP) ratio of 0.37 was considered the upper limit of normal. MAIN OUTCOME MEASURES: Enhancement in the SP/AP ratio from a normal baseline value to > 0.37 after oral salt loading was indicative of a positive test. RESULTS: None of the ears from control subjects had a positive salt load electrocochleogram, and one or both ears in 38% of the patients in the study group with normal baseline SP/AP ratios and symptoms of inner ear fluid imbalance converted to abnormal. The mean SP/AP ratio of the control group for the conditions before and after salt-load was not statistically different (p = 0.48), although the difference in the mean SP/AP ratio in the study group after salt loading was statistically significant (p = 1.329 x 10(-5)). CONCLUSIONS: A group of patients who reported vertigo with no localizing abnormalities had a statistically significant increase in the mean SP/AP ratio after ingestion of a large quantity of sodium chloride. A modest percentage had elevation of the SP/AP ratio above the upper limit of normal for our audiovestibular lab. The localization of a "salt-senstitive" ear could assist the clinician in the management of these difficult problems with long-term medical therapy or surgical treatment when alternative measures fail.

Adolescent↗

The use of trabeculectomy to study the pharmacological modulation of ophthalmic wound healing.

A trabeculectomy model was developed to test the efficacy of a putative interleukin-1 blocker on the modulation of ophthalmic wound healing in the pigmented rabbit. The corticosteroid, methylprednisolone acetate, was used as a positive control and was effective in prolonging the time to failure of the trabeculectomy. The experimental compound CK-103A was found to be more efficacious than methyl prednisolone acetate. CK-103A increased the time of failure by 79%, with no side effects at the doses tested to date.

Animals↗

Effects of interleukin-1 blockers on ophthalmic wound healing in a rabbit model of trabeculectomy.

A trabeculectomy model was used to test the efficacy of some Interleukin-1 blockers on the modulation of ophthalmic wound healing in the pigmented rabbit. The corticosteroid, methyl prednisolone, was used as a positive control and was effective in prolonging the time to failure of the trabeculectomy by 21%. The experimental compounds CK-17, CK-101A, CK-102 and CK-103A were more efficacious than vehicle control at prolonging the number of days before failure of the trabeculectomy by 55%, 55%, 30% and 79%, respectively. The CK- compounds increased the amount of time before failure of the fistula, with no side effects at the doses tested to date.

Acridines↗

The anticonvulsant activity of D-cycloserine is specific for tonic convulsions.

D-Cycloserine has been shown to exert anticonvulsant activity in maximal electroshock seizures. The purpose of the present study was to evaluate the spectrum of D-cycloserine anticonvulsant activity using other experimental models of epilepsy. D-Cycloserine induced a dose-related decrease in the incidence of tonic convulsions induced by 120 mg/kg of pentylenetetrazol. The ED50 of D-cycloserine for the inhibition of the tonic convulsions was 109 mg/kg. The anticonvulsant activity was specific for the D-isomer at L-cycloserine (400 mg/kg) had no effect on the tonic convulsions. D-Cycloserine had no effect on the pentylenetetrazol-induced clonic convulsions induced by either 70 or 120 mg/kg pentylenetetrazol, electrically induced nonkindled hippocampal seizures or kindled amygdala seizures. D-Cycloserine had no effect on strychnine-induced tonic convulsions. These results indicate that D-cycloserine is inactive against clonic convulsions and may be active only against tonic convulsions mediated by brainstem sites.

Animals↗