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Biomedical subjects

William B Armstrong

Publications and source records attributed to William B Armstrong.

14 recordsLinked to original sources

In vivo optical coherence tomography of the human oral cavity and oropharynx.

Optical coherence tomography (OCT) is an evolving imaging modality that combines interferometry with low-coherence light to produce high-resolution tissue imaging. Cross-sectional in vivo images were obtained using an OCT device consisting of a Michelson interferometer, 1.3-microm broadband light source, and a handheld fiberoptic imaging probe. Image pixel resolution approached 10 microm. The mucosa of the oral cavity and oropharynx were examined in 41 patients during operative endoscopy. Optical coherence tomographic imaging was combined with endoscopic photography for gross and histologic image correlation. Optical coherence tomographic images of the oral cavity and oropharynx provided microanatomical information on the epithelium, basement membrane (BM), and supporting lamina propria (LP) of the mucosa. Normal microstructures identified in these tissues included an overlying keratin layer, papillae, ducts, glands, and blood vessels. Regions of pathologic features studied included mature scar, granulation tissue, mucous cysts, leukoplakia, and invasive cancer. Optical coherence tomographic imaging showed distinct zones of normal, altered, and ablated tissue microstructures for each pathologic process studied. Abnormal findings were directly compared with regions of normal tissue or conventional histopathologic features when tissue for analysis was available. This study provides a composite series of in vivo OCT images of the oral cavity and oropharynx in a variety of normal regions and pathologic states as well as outline future applications of OCT technology.

Adult↗

Propofol lipemia mimicking chyle leak during neck dissection.

BACKGROUND: Propofol is an intravenous agent used in anesthesia. Lipemia is an uncommon adverse effect of propofol infusion. METHODS: A patient undergoing neck dissection for recurrent chordoma had intraoperative lipemia develop after prolonged propofol infusion. RESULTS: Lipemia gave blood in the surgical field a milky appearance resembling chyle, but no chyle leak was present. Lipemia was confirmed by drawing a sample of blood and leaving it to stand. Layering of the blood with a milky white upper layer was observed. Analysis of a second sample of blood revealed a high lipemic index. CONCLUSIONS: Lipemia is an uncommon adverse effect of propofol infusion, which may give blood a milky appearance and be confused for a chyle leak in a dissected neck. Identification of lipemia is also important because there is a risk of acute pancreatitis, and it may represent the early stage of propofol infusion syndrome.

Anesthetics, Intravenous↗

Optical coherence tomography of laryngeal cancer.

OBJECTIVES: Optical coherence tomography (OCT) is a high-resolution optical imaging technique that produces cross-sectional images of living tissues using light in a manner similar to ultrasound. This prospective study evaluated the ability of OCT to identify the characteristics of laryngeal cancer and measure changes in the basement membrane, tissue microstructure, and the transition zone at the edge of tumors. MATERIALS AND METHODS: One hundred thirty-three patients underwent OCT examination during surgical endoscopy of the head and neck. Twenty-two patients with laryngeal cancer or a history of laryngeal cancer were imaged with a fiberoptic OCT system. Tumor and adjacent transition zones were imaged along with uninvolved subsites. OCT images were correlated with histopathology. RESULTS: Twenty-six OCT examinations were performed in 22 patients. Basement membrane disruption was seen in 18 subjects, all of whom had histology showing classic features of cancer. A transition zone to uninvolved epithelium at the tumor periphery was also often observed. In six studies, benign or premalignant processes were histologically confirmed. In three thin, superficial lesions, an intact basement membrane was observed. The basement membrane could not be identified in three other bulky exophytic, premalignant lesions, primarily because of increased superficial signal backscattering observed in pathologic tissues. CONCLUSIONS: OCT clearly identifies basement membrane violation from laryngeal cancer and can identify transition zones at the cancer margin. In bulky exophytic lesions, OCT signal may not penetrate deeply enough to show the basement membrane, but for many suspicious lesions that require exclusion of cancer, OCT shows potential for assisting in diagnostic assessment.

Aged↗

Can a marker be a surrogate for development of cancer, and would we know it if it exists?

Carcinogenesis proceeds through a very long preclinical period. Our collective hope is that multiple opportunities exist for chemoprevention to arrest or reverse progression towards malignancy. In the hope of faster progress with fewer subjects and lower total cost, much effort is being expended on the search for reliable biomarkers to predict the likelihood of developing cancer and/or to signal the effectiveness of chemopreventive therapy. Considerable attention is paid to identifying those markers that can act as surrogate markers for cancer development, since favorable modulation of the surrogate end-point biomarker (SEBM) may demonstrate effectiveness of a putative preventive treatment. However, the complexity of the biology challenges our ability to measure the effectiveness of attempts to arrest or reverse carcinogenesis, other than through costly and time-consuming prospective trials with disease state as the endpoint. Despite much work, to date no prehistologic biological or molecular intermediate marker has been validated for sporadic cancers. Several factors accounting for the difficulties encountered in SEBM development are reviewed. Discussion is focused on the common thread of the complexity of the underlying biological changes in carcinogenesis limiting the effectiveness of any single biomarker. Additionally, the incidence of sporadic cancers is also low, further limiting the positive predictive value of any putative prognostic marker. Recent successes in development of chemopreventive agents show the concept is valid and worth pursuing, but the current strategies to develop biochemical and genetic markers to identify surrogate biomarkers is flawed, and need to be reassessed in light of the difficulties faced over the last 20 years.

Anticarcinogenic Agents↗

A novel laryngoscope instrument stabilizer for operative microlaryngoscopy.

OBJECTIVE: To evaluate and optimize the design of a removable and inexpensive internal stabilization device to reduce the effect of intention tremor during laryngeal microsurgery. STUDY DESIGN AND SETTING: In this laboratory investigation, stabilizers were designed and constructed to allow a nonobstructing view of the surgical field, permit simple insertion and removal, and accommodate microsurgical instruments. Prototype stabilizers were tested by using a Dedo laryngoscope, a measurement grid, and video recording equipment, which recorded instrument tremor within the magnified operative field for later analysis. Physicians also rated instrument stability, mobility, visualization, and ease of use on a survey form. RESULTS: Instrument tremor was reduced approximately 90%, with little obstruction of view of the surgical field. Instrument range of motion was reduced but improved rapidly as the stabilizer bar was moved further from the tip of the laryngoscope. CONCLUSIONS: Use of a stabilization device in the laryngoscope lumen reduces instrument tremor and has the potential to improve surgical performance during laryngeal microsurgery. EBM RATING: B-3.

Equipment Design↗

Measurement of morphologic changes induced by trauma with the use of coherence tomography in porcine vocal cords.

BACKGROUND AND OBJECTIVE: To evaluate the ability of optical coherence tomography (OCT) (a noncontact, high-resolution imaging technique that generates detailed cross-sectional images of tissue structure) to image and document acute response to trauma in the larynx. MATERIALS AND METHODS: Porcine larynges were dissected to expose the vocal cords. Vocal cords were imaged with 1310 nanometer (nm) light source with a bandwidth of 75 nm at 1 frame/second (s). Vocal cord injuries were simulated by applying topical phenolic acid, injecting titanium dioxide into the submucosa, and carbon dioxide laser irradiation. RESULTS: The epithelium, basement membrane, and lamina propria were clearly delineated, and the effect of each intervention could be monitored as lesions progressed. The OCT image corresponded closely with histology. CONCLUSION: OCT is a powerful imaging tool with the potential for use in real time and has potential for multiple clinical applications in the larynx.

Administration, Topical↗

In vivo optical coherence tomography of the human larynx: normative and benign pathology in 82 patients.

OBJECTIVES: Optical coherence tomography (OCT) is an emerging imaging modality that combines low-coherence light with interferometry to produce cross-sectional images of tissue with resolution about 10 mum. Patients undergoing surgical head and neck endoscopy were examined using a fiberoptic OCT imaging probe to study and characterize microstructural anatomy and features of the larynx and benign laryngeal pathology in vivo. STUDY DESIGN: Prospective clinical trial. MATERIALS AND METHODS: OCT imaging of the larynx was performed in 82 of 115 patients who underwent surgical endoscopy for various head and neck pathologies. The OCT device employs a 1.3 microm broadband light source (FWHM, 80 nm). The frame rate is 1 Hz. Imaging was performed using a handheld probe placed in near contact with the target site. The maximum axial and lateral dimensions for the region of interest imaged were 2.5 mm x 6 mm, with resolutions of 10 microm. Simultaneously, conventional endoscopic images were obtained to provide anatomic correlation with OCT images and histology. Optical micrometry was performed to measure the epithelium thickness. RESULTS: Systematic OCT imaging of laryngeal structures and subsites provided information on the thickness of the epithelium, integrity of the basement membrane, and structure of the lamina propria. Microstructural features identified included glands, ducts, blood vessels, fluid collection/edema, and the transitions between pseudostratified columnar and stratified squamous epithelium. The mean epithelial thickness of laryngeal subsites was calculated: true vocal cord (129 microm), false vocal cords (124 microm), aryepiglottic fold (177 microm), subglottis (98 microm), and epiglottis (185 microm). True vocal cord pathology imaged included Reinke's edema, papillomatosis, polyps, mucous cysts, and granulation tissue. Subglottic imaging identified boundaries between epithelium, lamina propria, and cartilage. The OCT images compared favorably with conventional histopathology. CONCLUSION: OCT has the unique ability to image laryngeal tissue microstructure and can detail microanatomic changes in benign, premalignant, and malignant laryngeal pathologies. OCT holds the potential to guide surgical biopsies, direct therapy, and monitor disease, particularly when office-based systems are developed. This is a promising imaging modality to study the larynx.

Biopsy↗

Bioactive suture: a novel immunotherapy for head and neck cancer.

PURPOSE: We have proposed to characterize the mechanism through which bioactive surgical sutures generate a T(H)1 immune response and to define the immune-stimulating half-life of the sutures. EXPERIMENTAL DESIGN: Bioactive sutures of interferon gamma (IFNgamma), interleukin 2 (IL-2), anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNgamma sutures were used to stimulate lymphocytes from normal donors and from head and neck cancer patients in vitro over a 24-day period. Cell supernatants were analyzed by ELISA, and T cells were phenotyped to characterize the immune response generated. Intracellular cytokine staining was performed to measure the expansion of flu-specific T cells. Electromobility shift assay and supershift assay were used to measure the intranuclear DNA binding activity of nuclear factor kappaB and its p65 subunit in T cells activated by sutures in the presence and absence of a proteasome inhibitor, MG-132. RESULTS: Anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNgamma generated a prolonged T(H)1 immune response for 18 days in vitro. Anti-CD3/CD28 expanded flu-specific T cells. Activated T cells demonstrated enhanced CD40 ligand (CD40L) expression within 72 hours of stimulation, which stimulated other cells to secrete IL-12. Stimulated T cells demonstrated increased intranuclear expression of nuclear factor-kappaB, which was blocked by MG-132, and also reduced CD40L and IL-12 expression. CONCLUSIONS: This is the first report to demonstrate that bioactive surgical sutures can generate a prolonged T(H)1 immune response and expand flu-specific T cells. Bioactive sutures, which are primarily a T-cell stimulant, also stimulated other cells to secrete IL-12 and prolonged the immune response. Sutures may provide a novel in situ stimulating strategy for enhancing the immune system of cancer patients.

Adult↗

Mandibular reconstruction: are two flaps better than one?

This study compared the combined iliac and ulnar forearm flaps with the osteomusculocutaneous fibular free flap for mandibular reconstruction. A retrospective study of 40 patients who had oromandibular reconstruction was performed, of whom 23 patients had a combined iliac crest without skin and ulnar forearm free flap. Seventeen patients had an osteomusculocutaneous free fibular flap. Ten women and 30 men with a mean age of 57.5 years comprised this study population. Ninety percent of the cases were squamous cell carcinoma (55%, T4), of which 11% were recurrent tumors. Anterolateral mandibular defects constituted 52.9% of the fibular reconstructions and 60.9% accounted for the iliac/ulnar reconstructions. The mean bone gaps were 8.79 cm and 8.95 cm respectively. Functional evaluation was based on the University of Washington Questionnaire through phone calls and personal communication. The mean hospital stay was 15.43 days and 10.09 days for the fibular and iliac/ulnar flaps respectively. The facial artery (64.7%) and facial vein (60%) were the main recipient vessels for the fibular reconstructions whereas the external carotid artery (95.6%) and the internal jugular vein (66.7%) were the main recipient vessels for the iliac/ulnar reconstruction. Overall flap survival was 96.8% (100% of fibular flaps and 95.65% of iliac/ulnar flaps). Two flaps were lost in the iliac/ulnar series because of unsalvageable venous thrombosis. Local complications for the iliac/ulnar flaps were 30.4% but were 5.9% for the fibular reconstructions. Function such as speech, swallowing, and chewing were notably better in the fibular than the iliac/ulnar group in 23 of the patients tested. The cosmetic acceptance of 77.8% of the fibular flaps was judged to be excellent and good, whereas 71.4% of the iliac/ulnar flaps were rated good. It appears that within this study population the free osteomusculocutaneous fibular flap had fewer local complications and a higher flap survival rate than the combined iliac/ulnar forearm flaps. Overall functional outcome was also improved. The use of the double flap may be appropriate in massive oromandibular defects, but may be less appropriate in more modest functional reconstructions of mandibular defects.

Adult↗

Development of the Bowman-Birk inhibitor for oral cancer chemoprevention and analysis of Neu immunohistochemical staining intensity with Bowman-Birk inhibitor concentrate treatment.

OBJECTIVES/HYPOTHESIS: Cancer chemoprevention is a rapidly evolving approach to reverse or inhibit carcinogenesis, and there is active interest in development of effective chemopreventive agents against head and neck cancers. The retinoids are archetypal chemopreventive agents for oral premalignant lesions. They have significant clinical effect, but widespread use is limited by significant clinical toxicity. The Bowman-Birk Inhibitor is one of several nontoxic compounds exhibiting both potent anticarcinogenic activity and minimal toxicity. The purposes of the study were to summarize the preclinical and clinical development of Bowman-Birk Inhibitor and a Bowman-Birk Inhibitor concentrate against oral premalignant lesions and to evaluate Neu immunohistochemical staining intensity for lesions and simultaneously obtained biopsy specimens of normal-appearing mucosa from the Phase IIa Bowman-Birk Inhibitor concentrate oral leukoplakia chemoprevention trial. STUDY DESIGN: Part I is a selected literature review. Part II is a retrospective analysis of pathological specimens prospectively obtained from the Phase IIa clinical trial of Bowman-Birk Inhibitor concentrate. METHODS: Thirty-two sets of biopsy specimens from lesions and uninvolved oral mucosa before and after treatment with Bowman-Birk Inhibitor concentrate in doses ranging from 200 to 1066 chymotrypsin inhibitory units were examined in blinded fashion for Neu immunohistochemical staining intensity using the 3B-5 monoclonal antibody. Staining intensity scores among the lesion and control biopsy specimens before and after Bowman-Birk Inhibitor concentrate treatment were analyzed and compared with previously obtained values for serum Neu, oral mucosal cell Neu, protease activity, and clinical response to treatment. RESULTS: Mean Neu staining score was significantly higher in lesions compared with uninvolved mucosa (P <.001). Pretreatment staining scores for biopsy specimens of lesions and control biopsy specimens of normal-appearing tissues were correlated (Spearman correlation coefficient [r] = 0.375, P =.045), but no correlation between lesion and control biopsy specimen scores was evident after treatment. The change in Neu staining score with Bowman-Birk Inhibitor concentrate treatment in control site biopsy specimens demonstrated an inverse relationship of change in lesion area with Bowman-Birk Inhibitor concentrate treatment (Spearman r = -0.493, P <.007). CONCLUSION: Bowman-Birk Inhibitor concentrate shows promise to become an effective nontoxic chemopreventive agent based on results of extensive preclinical studies, and Phase I and Phase IIa clinical trials. Bowman-Birk Inhibitor concentrate has dose-related clinical activity against oral leukoplakia and modulates levels of Neu and protease activity. The current investigation identified increased Neu staining intensity in hyperplastic lesions compared with simultaneously obtained biopsy specimens of normal-appearing mucosa both before and after Bowman-Birk Inhibitor concentrate treatment. This finding supports prior observations that increased Neu expression is present in a subset of oral premalignant lesions and head and neck cancers. The trend of increased Neu staining score in control biopsy tissues of subjects exhibiting decreased lesion area following Bowman-Birk Inhibitor concentrate treatment raises questions about the mechanisms of Bowman-Birk Inhibitor concentrate action. One possible explanation is that Bowman-Birk Inhibitor stabilizes the extracellular domain of Neu, thereby preventing receptor truncation and internalization. Further study of modulation of Neu and protease activity by Bowman-Birk Inhibitor concentrate treatment may provide insights into the role of proteases and protease inhibitors in oral premalignant lesions and the mechanisms underlying Bowman-Birk Inhibitor concentrate effects. A Phase IIb randomized, placebo-controlled clinical trial to determine the clinical effectiveness of Bowman-Birk Inhibitor concentrate and further evaluate these candidate biomarkers is under way.

Animals↗

Ultrashort pulse laser ossicular ablation and stapedotomy in cadaveric bone.

BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate the ablation of ossicular tissue using a 1,053 nm Ti:Sapphire chirped pulse amplifier laser system configured to deliver ultrashort pulses of 350 femtoseconds (fs) (3.5x10(-13) seconds) in cadaver temporal bone. STUDY DESIGN/MATERIALS AND METHODS: Ablation of the formalin-fixed incus and stapes was performed using an ultrashort pulse laser (USPL) (0.4 mm beam diameter, pulse fluence of 2.0 J/cm2, and pulse repetition rate of 10 Hz). The ablation rate was measured using optical micrometry, and crater surface morphology examined using scanning electron microscopy. RESULTS: The laser produced precise bone ablation at a rate of 1.26 microm/pulse, with almost no evidence of thermal damage, and very little evidence of photomechanical injury. CONCLUSIONS: Ultrashort pulse lasers may provide a useful clinical tool for otologic and skull base surgery, where precise hard tissue ablation is required adjacent to critical structures.

Cadaver↗

The effect of optical design on micromanipulator spot size using CO2 laser irradiation.

OBJECTIVE: The study goal was to compare the laser spot size created using reflective and refractive micromanipulators with a CO(2) laser and to determine the sensitivity of spot size to laser power. STUDY DESIGN AND SETTING: A CO(2) laser and operating microscope (400-mm focal length) was coupled to either a reflective (Cassegrain-like) or refractive micromanipulator. Laser spot size was determined by measuring the region of ablation created by laser irradiation of wood (dry tongue depressors), exposed photographic film, and agar gel using optical micrometry. Laser power varied from 0.5 to 20 W with pulse durations of 0.1 and 0.5 second. RESULTS: The reflective micromanipulator demonstrated overall smaller spot sizes for a given laser power and lower incremental change in spot size with increasing power. The reflective design demonstrated less sensitivity to increases in laser power. CONCLUSIONS: Micromanipulator optical design can result in significant differences in laser spot size. The reflective device used in this study demonstrated less sensitivity to increasing laser power.

Algorithms↗