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Biomedical subjects

P H Ward

Publications and source records attributed to P H Ward.

At least 19 recordsLinked to original sources

Point-touch technique of botulinum toxin injection for the treatment of spasmodic dysphonia.

Intralaryngeal injections of botulinum toxin (Botox), under electromyographic guidance, have emerged as an effective treatment for adductor spasmodic dysphonia. To remain effective, these injections must be repeated every 3 to 9 months as the symptoms recur. One drawback to the current method is the need for electromyographic confirmation of needle placement into the thyroarytenoid muscle. This report describes an anatomic approach to Botox injection that requires only flexible nasopharyngeal endoscopy and careful evaluation of the anatomic landmarks. This technique has been used successfully on 13 patients, and objective pretreatment and posttreatment measures are reported.

Adult

Metastatic head and neck malignancy treated using MRI guided interstitial laser phototherapy: an initial case report.

Interstitial laser phototherapy (ILP) guided by magnetic resonance imaging (MRI) may become an attractive adjunctive modality for the treatment of deep and surgically inaccessible tumors of the head and neck when accurate methods of laser dosimetry and "real-time" monitoring techniques with the MRI are introduced. We recently demonstrated in ex vivo and in vivo models, a linear relationship between levels of laser energies, thermal profiles, MR signal intensity changes, and histopathological tissue damage. Results of treatment in a patient with an unresectable large right jugulodigastric metastatic squamous carcinoma using new approach of MRI guided ILP are now reported. The patient complained of significant right-sided neck pain and headaches secondary to a rapidly growing metastatic lymphadenopathy which recurred after previous surgery, radiation, and chemotherapy. Two treatment sessions were used at an interval of 2 weeks. Each treatment was performed in the MRI suite under heavy sedation. Using a 600-microns bare fiber of the Nd:YAG laser implanted interstitially under MR guidance, the metastatic node was treated at three sites. T1- and T2-weighted images were performed prior to, immediately after, 24 and 48 hours, and 4, 5, 7, 9, 16, and 25 days post-treatment. Successful relief of pain and growth arrest of this node was observed after the second treatment and at the 3-month follow-up. These results demonstrate that this technique of ILP guided by MRI may be feasible in humans, and will become clinically practical when appropriate methods of dosimetry and instrumentation are developed.

Aluminum Silicates

Laser dyes for experimental phototherapy of human cancer: comparison of three rhodamines.

The mitochondrial dye Rhodamine 123 (Rh-123) has been shown to be an effective photosensitizer for argon-laser irradiation of some types of human cancer cells in vitro. We reported that 514.5-nm laser illumination of Rh-123 sensitized human melanoma, and squamous carcinoma cells strongly inhibited tumor-cell proliferation as measured by decreased 3H-thymidine (3H-T) uptake in vitro and may eradicate some tumors when grown as transplants in nude mice. However, several other human tumors were resistant to Rh-123 laser therapy in vitro and in vivo. In the current study, it was possible to obtain 100- to 1000-fold increased sensitivity to 514.5-nm laser illumination by replacement of Rh-123 with the cationic rhodamine dyes Rh-3G and Rh-6G. Cell viability was decreased over 95% and 3H-T incorporation reduced at least 80% by laser phototherapy after sensitizing tumor cells with 1 micrograms/mL Rh-123, 0.01 microgram/mL Rh-3G, or 0.001 microgram/mL Rh-6G. However, Rh-123 alone did not decrease 3H-T uptake significantly unless present at over 10- to 100-fold higher levels than Rh-3G, respectively. The tumor cell dye uptake level was measured by N-butanol extraction and absorption scans at 400 to 600 nm. The results revealed that dye uptake was more rapid, and retention of Rh-3G and Rh-6G was 5- to 10-fold higher than for Rh-123 in the human tumor cells. The data suggest that Rh-3G and Rh-6G may be highly sensitive chromophores for laser phototherapy of human cancer cells.

Adenocarcinoma

Positron emission tomography: a new, precise imaging modality for detection of primary head and neck tumors and assessment of cervical adenopathy.

Positron emission tomography (PET) has been shown to be effective in detecting intracranial malignancies based on cerebral glucose metabolism. To evaluate the ability of PET to detect extracranial head and neck neoplasms and cervical metastases, 16 patients with primary squamous cell carcinomas were examined. All patients received preoperative computerized tomography (CT) and magnetic resonance imaging (MRI) scans and underwent PET evaluation using intravenous 18F-2-fluoro-2-deoxy-D-glucose (FDG). Histopathologic analysis compared tumor invasion and positive lymph nodes with findings on MRI, CT, and PET images. All primary tumors were delineated by PET, while MRI and CT failed to detect one superficial tumor involving the anterior tongue. Ten nodes were detected by CT and MRI versus 12 nodes demonstrated by PET. PET is highly effective in detecting head and neck carcinomas as well as metastatic cervical lymph nodes. In addition, PET may be useful in evaluating postsurgery and postradiotherapy patients for recurrent and new primary tumors.

Adult

Biodistribution of rhodamine-123 in nude mice heterotransplanted with human squamous cell carcinomas.

Rhodamine-123 uptake and release was determined in nu/nu mice heterotransplanted with P3 human squamous carcinomas to assess its value as an in vivo laser photosensitizer for treatment of solid tumors. Following intraperitoneal injection of Rh-123 (1 micrograms/g of body weight), mice were killed at 2, 4, 6 and 24 hours, and 3 and 7 days postinjection. The peak concentrations of Rh-123 per milligram of tissue measured by fluorescence spectrophotometry was distributed as follows: kidneys greater than spleen greater than intestine greater than stomach greater than liver greater than tumor greater than skin greater than skeletal muscles greater than lung greater than heart greater than blood greater than brain. No preferential uptake or retention of Rh-123 by tumors was observed. However, a longer retention with higher concentrations of the dye was seen in normal skin as opposed to P3 tumors from 4 hours to 7 days postinjection with Rh-123. The elimination of Rh-123 was rapid, with the dye falling to less than 2% of peak concentration at 7 days postinjection. Knowledge of Rh-123 biodistribution in tumors and other tissues suggests that optimal timing after injection of this dye may allow selective photodiagnosis and photodynamic therapy of tumors with the argon laser.

Animals

Nasopharyngeal carcinoma: treatment results with primary radiation therapy.

One hundred three patients with nasopharyngeal carcinoma were treated with radiotherapy at UCLA Medical Center from January 1955 to December 1990. Overall survival, disease-free survival, and local control rates were analyzed. In addition, survival from 1955 to 1978 and from 1979 to 1990 were evaluated. Overall 5- and 10-year actuarial survival rates for all patients were 58% and 47%, respectively. Disease-free survival rates at 3 and 5 years were 45% and 30%, respectively. Local, persistent, or recurrent disease in the nasopharynx was the primary cause of failure, occurring in 32% of patients and correlating with the initial tumor size (T stage). Twenty-four percent of patients developed distant metastases, which correlated with nodal status but not with T stage. Seventy-nine percent of patients failed either locally or distally by 4 years. Sex, race, age, and T and N stage categories were evaluated as prognostic variables in terms of survival. Control of primary disease is important in determining long-term outcome. Modern imaging techniques have greatly assisted in the evaluation of disease extent and treatment options.

Adolescent

Oxygen-derived free radicals mediate liver damage in rats subjected to tourniquet shock.

The placement of rubber band tourniquets upon rat hind-limbs for 5 h followed by reperfusion of the extremities results in a severe form of circulatory shock characterized by hypotension and death within 24 h of tourniquet release. Oxidative damage to muscle tissue is an early consequence of hind-limb reperfusion on tourniquet release, yet this local damage does not explain the lethal hypotensive shock state which evolves within the next 24 h. Multiple system organ failure (MSOF), of as of yet unknown causes, is usually described in relation to several shock states. It has been suggested that injured or necrotic tissue may activate neutrophils, platelets, and the coagulation system leading to embolization in remote tissues. Effective decreases in hepatic blood flow have been observed in several forms of sepsis which precedes the biochemical evidence consistent with an ischemic insult of the liver. In support of our original hypothesis, that organ failure has its genesis in a primary perfusion abnormality with secondary ischemic organ injury, herein we have assessed the possibility that oxygen-derived free radicals are generated in the liver of rats after reperfusion of their hind-limbs on release of the tourniquets. We report on the protective effects of allopurinol (ALLO) and a mixture of superoxide dismutase (SOD) catalase (CAT) and dimethylsulfoxide (DMSO) on liver free sulfhydryl content (SH), thiobarbituric acid-reactive substances (TBARS), and on the release of aspartic acid (AsT) and alanine aminotransferase (AlT) activities, and of alkaline phosphatase during a 5 h tourniquet period and after 2 h of reperfusion of the hind-limbs. During the hind-limb ischemic period hepatis tissue SH levels remained essentially constant during the first hour (6.02 +/- 0.36 to 5.65 +/- 0.20 mumoles/g wet tissue), and decreased significantly, over and above the normal circadian decrease of liver glutathione levels, to 4.02 +/- 0.69 mumoles/g wet tissue after the third hour and remained lowered until tourniquet release. A further significant decrease (3.11 +/- 0.49 mumoles/g wet tissue) was observed after 2h of reperfusion. TBARS production remained constant during the 5 h hind-limb ischemic period (168.4 +/- 37.3 mumoles/g wet tissue) and rose by 55% to 261.7 +/- 55.8 mumoles/g wet tissue after 2 h of tourniquet release. ALLO, but not the SOD-CAT-DMSO combination, protected hepatic SH loss during the hind-limb ischemic insult, yet both offered protection after 2 h of tourniquet release.(ABSTRACT TRUNCATED AT 400 WORDS)

Alanine Transaminase

Differential diagnosis of virus-like particles in the human inner ear.

The entire endolymphatic duct and sac as well as the vestibular epithelia were obtained from four patients with Meniere's disease during translabyrinthine (TL) eighth nerve section and from 12 patients undergoing TL resection of acoustic schwannomas. After these specimens were processed for routine transmission electron microscopy (TEM), they were studied for morphologic evidence of viral infection. Although no virus particles were identified, numerous regularly occurring cell components and artifacts were found to morphologically mimic viruses. An atlas of these structures is presented.

Diagnosis, Differential

Vocal fold medialization by surgical augmentation versus arytenoid adduction in the in vivo canine model.

There are a variety of methods for treating unilateral vocal cord paralysis, but to date there have been few studies that compare these phonosurgical techniques by using objective measures of voice improvement. Vocal efficiency is an objective voice measure that is defined as the ratio of the acoustic power produced by the larynx to the subglottic air power. Vocal efficiency has been found to decrease with glottic disorders such as vocal cord paralysis and carcinoma. This study compared the effects of vocal fold medialization by surgical augmentation to those of arytenoid adduction on the vocal efficiency, videostroboscopy, and acoustics (jitter, shimmer, and signal-to-noise ratio) of a simulated unilateral vocal cord paralysis in an in vivo canine model. Arytenoid adduction was superior to surgical augmentation in vocal efficiency, traveling wave motion, and acoustics.

Animals

Technique for transmission and immunoelectron microscopy of the human endolymphatic sac and vestibular epithelia.

A surgical technique is presented to obtain the entire vestibular aqueduct, containing the endolymphatic duct and sac as well as the vestibular epithelia, from the maculae and cristae during labyrinthectomy. The inner ear tissue was fixed in 3% glutaraldehyde, decalcified in 0.1 mol/L Na-EDTA, and routinely processed for transmission electron microscopy, including post-fixation with osmium tetroxide. Postembedding protein A-colloidal gold immunoelectron microscopy was performed after exposure of cellular antigenic sites by sodium metaperiodate. To validate this technique, thin sections from the crista ampullaris and the endolymphatic sac were incubated with antibodies raised against S-100, a protein present in specific types of neural tissue. Specific immunoreactivity was observed in the crista ampullaris, but not in the endolymphatic sac. The surgical biopsy technique described provides a means for the neuro-otologist to collect inner ear tissue from surgical patients that can be used for pathological studies using immunohistochemistry and electron microscopy.

Biopsy

Cell and molecular anatomy of nicotinic acetylcholine receptor subunits and calcitonin gene-related peptide in the rat vestibular system.

In this report we demonstrate the pattern of calcitonin gene-related peptide (CGRP) mRNA and immunoreactivity in the central and peripheral vestibular system of the rat, using a CGRP cRNA probe and a polyclonal CGRP antiserum. We present evidence that somata in all regions of efferent vestibular neurons contain CGRP based on the correspondence between in situ hybridization (mRNA) and immunohistochemistry (mRNA translation product). CGRP immunohistochemistry (CGRPi) and in situ hybridization confirm that CGRPi axons and terminals present in the vestibular neuroepithelium are efferent in origin. Immunoelectron microscopy revealed an extensive innervation of the afferent vestibular pathway by CGRPi terminals that was not limited to the primary afferent chalice, as previously reported by Tanaka et al. (Brain Res 1989;504:31-5). An efferent neuromodulatory role of CGRP can be inferred from the distribution of terminals found on the primary afferent fibers, and type I and type II hair cells. In addition, we present evidence that nicotinic acetylcholine receptor (nAChR) subunit mRNA is expressed by primary afferent cell bodies. On the basis of these data, a hypothetical molecular mechanism of vestibular efferent modulation of the primary afferent pathway is proposed.

Animals

Future directions of laser phototherapy for diagnosis and treatment of malignancies: fantasy, fallacy, or reality?

A new and highly promising adjunctive modality for the diagnosis and therapy of malignancies is under development using lasers and tumor targeting dyes. To reach the eventual goal of clinical treatment, several current "fantasies and fallacies" regarding laser applications in medicine must be identified and their problems clearly outlined. A multidisciplinary scientific approach is also required to enable the clinical practicality of this laser targeting approach. Many new dyes and laser wavelengths are being tested to improve specific tumor uptake and/or retention, lower systemic toxicity, increase tissue penetration, and identify fluorochromes with synergistic properties to further enhance laser tumoricidal effects. Rapid technological advancements in magnetic resonance imaging may now provide an extremely sensitive way to detect and monitor laser-tissue effects, and allow efficient interstitial laser phototherapy of deep and sometimes inaccessible tumors. The current and future prospectives of the emerging field of laser phototherapy are described.

Coloring Agents

Molecular biology of the vestibular system.

Molecular biology of the vestibular system has been limited by a number of technical difficulties including fixation, decalcification of the temporal bone and the small size of specific structures relative to their surroundings. In situ hybridization histochemistry and immunoelectron microscopy allow the subcellular study of gene expression and gene products, respectively. We developed the methodologies necessary to apply these techniques to the central and peripheral vestibular systems. The central and temporal bone distributions of the neuropeptide calcitonin gene-related peptide (CGRP) mRNA and two genes coding for gap junction proteins, connexin C32 and C43 mRNA, were studied. The cellular distributions of these mRNAs are presented. In addition, examples of pre-embedding and postembedding immunoelectron microscopy are presented demonstrating the usefulness of these techniques in studying the subcellular localization of specific antigens. The ultrastructural innervation of the vestibular periphery by the efferent neuropeptide CGRP and ultrastructural evidence of glycoprotein secretion by the human endolymphatic sac is presented.

Animals

Evaluation of mandibular tumor invasion with magnetic resonance imaging.

Evaluating the extent of tumor invasion of the mandible is clinically important in the management of mandibular tumors. Conventional imaging studies including panoramic radiography, bone scans, and computed tomography, as well as clinical evaluation can be unreliable in defining the extent of neoplastic marrow invasion. This study presents the initial UCLA, Los Angeles, Calif, experience with magnetic resonance imaging in evaluating mandibular invasion by benign and malignant neoplasms. Magnetic resonance imaging, using T1 and T2 images, was compared with conventional imaging methods in 11 patients with malignant lesions and nine patients with benign lesions. In all cases, magnetic resonance imaging most accurately determined the full extent of tumor invasion in the mandibular marrow spaces. Magnetic resonance imaging appears to be superior to offer clear benefits over conventional imaging methods, including computed tomography, for the evaluation of tumor invasion of the mandible.

Adult

Oxygen-derived free radicals mediate the cutaneous necrotizing vasculitis induced by epinephrine in endotoxin-primed rabbits.

To assess the possible role of oxygen-derived free radical in the pathogenesis of cutaneous necrotizing vasculitis (Thomas reaction) induced by epinephrine in endotoxin-primed rabbits, animals were treated with superoxide dismutase (intraperitoneal or local), catalase, allopurinol, or ibuprofen 2 h before inducing the reaction. This is done by an earlobe intravenous injection (10 micrograms) of endotoxin followed by an intradermal injection (100 micrograms) of epinephrine in the shaved abdomen; 18-24 h later, a hemorrhagic-necrotic lesion can be observed at the site of the epinephrine injection. The reaction was completely inhibited by superoxide dismutase, catalase, and ibuprofen, while allopurinol afforded only partial protection. Thus, oxyradicals seem to participate in the pathogenesis of this reaction.

Animals

Re-evaluation of the role of the human endolymphatic sac in Menière's disease.

The role of endolymphatic sac (ES) dysfunction in the etiopathogenesis of Meniere's disease has remained controversial since the early 1900s. The first reports of the ultrastructural (transmission electron microscopy, TEM) pathology of the human ES in Meniere's disease have been published only in the last decade. These studies have been based on biopsies of the extraosseous (intradural) ES and in no cases has the TEM appearance of the intraosseous ES been described. Likewise the control material used has been from biopsies of extraosseous ES taken from patients with acoustic schwannomas. To date, no reports have compared the ultrastructure of the intrasosseous ES from normal control patients to patients with Meniere's disease. Since the intraosseous ES is believed to be the most active portion of the entire ES, studies were made of the ultrastructure of ten normal interosseous human ESs fixed immediately after death and obtained at autopsy (control material). Fourteen patients undergoing translabyrinthine (TL) neurotologic procedures (10, TL resection of acoustic schwannoma; 4, TL eighth cranial nerve section for Meniere's disease) had the entire vestibular aqueduct, containing the endolymphatic duct and the intraosseous ES, removed and processed for TEM. The roles of the epithelium, subepithelial space, and vasculature were morphologically studied to evaluate possible ES pathology in Meniere's disease and in patients with acoustic schwannoma. Wide anatomic variation in the distribution and density of the subepithelial connective tissue was observed in all groups. There was no difference in the TEM appearance of the intraosseous ES from normal controls and patients with eighth nerve schwannoma, nor was there any difference in the ES collagen deposition in patients with Meniere's disease. The ESs from two patients with Meniere's disease showed evidence of abnormal glycoprotein metabolism; one with possible hypersecretion and one with possible alteration of degradation of resorbed glycoprotein. The results of this preliminary study suggest that "perisaccular fibrosis" of the intraosseous ES was not a pathologic feature in these four cases of Meniere's disease and that alteration of ES glycoprotein secretion/resorption may be of etiopathologic significance.

Adult