T cell receptor beta chain gene rearrangement shared by murine T cell lines derived from a site of autoimmune inflammation.

Advances in our understanding of the structure and molecular biology of the T lymphocyte antigen-receptor have now made it feasible to study human autoimmune diseases using new approaches. One such approach involves cloning of T cells from sites of autoimmune pathology followed by identification of putative disease-related T cell oligoclonality at the level of the T cell receptor gene rearrangements. We have now tested the feasibility of this approach in an animal model of autoimmunity, murine experimental allergic encephalomyelitis (EAE). Spinal cord-derived, self (murine) myelin basic protein (MBP)-reactive T cell lines and sublines were analyzed at the level of their receptor beta chain rearrangements using Southern blots. We now report that the MBP-reactive T cell lines and sublines derived from the spinal cords of four of five SJL/J mice with EAE share a 14.5-kb rearranged T cell receptor beta 1 band on Southern blots. A spinal cord-derived T cell line that was reactive to purified protein derivative of tuberculin (PPD), several lymph node-derived ovalbumin- and PPD-reactive T cell lines, as well as one MBP-reactive spinal cord-derived T cell line did not share this 14.5-kb rearranged beta 1 band. These results suggest that analysis of the antigen receptors used by T cells cloned from sites of inflammation may be a useful initial approach for identifying pathogenetically relevant T cells in the study of certain human autoimmune diseases.

Some engineering aspects of insulin delivery systems.

The characteristics of electronically controlled insulin delivery systems are presented. Early experiments with an external system have shown promise in providing improved glycemic control over conventional methods of single or multiple subcutaneous insulin injections. The encouraging results with external insulin delivery systems have led to the development and early testing in dogs of an implantable system with remote controls to permit variable insulin flow rates. A number of questions remain to be answered before widespread experimentation with external and implanted insulin delivery systems is possible. There appears to be no major development problems with the engineering aspects of such systems.

Civilian air travel and the otolaryngologist.

Thousands of individuals fly commercial airlines and private aircraft daily. One airline boasts of serving more than 100,000 passengers each day. Of these individuals exposed to barometric alterations, an undocumented number will develop significant barotrauma and may seek help from an otolaryngologist. Although many otolaryngologists learn the mechanics and management of barotrauma as military flight surgeons, residents in otolaryngology usually receive no specific training in this area. Because private and commercial aviation are so common today, we believe that a basic knowledge of barometric changes experienced while flying is essential for the practicing otolaryngologist. These basic principles are covered in this presentation. Case histories will also be discussed. One patient, who presented with signs of perilymph fistula, including sensorineural deafness and abnormal ENG, recovered spontaneously.

The biphasic acoustic reflex: a new perspective.

The anatomic, neurologic, and physiologic characteristics of the middle ear structures have created confusion concerning the nature of the intraaural muscle reflex. After reviewing the relevant literature, we correlated this information with our studies of human temporal bones and computer analyses of the acoustic reflex responses of individuals with normal hearing. Our hypothesis is that although the stapedius is the initiator of the reflex and the primary contributor to ossicular chain fixation, the tensor tympani is responsible for the major observed response. The negative deflection present in normals tested on the impedance bridge is caused by the stapedius, whereas the large positive deflection is the result of the tensor tympani contraction. We postulate that proprioceptive feedback mechanisms located within the stapedius muscle and tendon permit and/or initiate tensor tympani contraction during acoustic stimulation.

Perilymphatic fistulas.

The oft-quoted dictum that clinical suspicion rather than any specific test leads to the diagnosis is confirmed by our study. Further work is needed to define the vestibular findings more precisely and to work out relationships between CSF and perilymph pressures. Temporal bone study will be necessary to document the double membrane break theory. Future study may include analysis of suspected fistula fluid to determine if it represents a mixture of perilymph and endolymph. From our study, fistulae may occur from minimal or no trauma. The presentation is usually subtle. Because no diagnostic test is available to assure correct diagnosis, one must maintain a high index of suspension. Diagnosis usually cannot be made until the ear is surgically explored. The low morbidity of an exploratory tympanotomy, coupled with the high positive to negative ratio of exploration and the high degree of successful results, leads the authors to encourage exploration. Indeed, the overall concensus is that many active fistulae remain undiagnosed because of the lack of suspension and the reluctance to explore an ear without a concrete preoperative diagnosis. The duration of the fistulae and the recurrent nature of the problem poses another diagnostic dilemma. The first positive exploratory tympanotomy for perilymphatic fistula often leaves the surgeon with a dichotomy of emotion from pride of a correct diagnosis to fear that perhaps his observations of the minute clear fluid seepage was an error. Reversal of patient symptoms quickly erases such fears and presumptive diagnosis of perilymphatic fistula becomes easier to make. Eventually, one begins to worry, "How many have I missed."

Otologic and otoneurologic injuries in divers: clinical studies on nine commercial and two sport divers.

In the past two decades, we have seen a great increase in the number of injuries from commercial and sport diving. During this time, our knowledge of the physiology and pathophysiology of diving has also increased. As a result, we now can accurately diagnose and successfully treat many of these injuries. Of the commercial and sport divers examined as pateints in the Department of Otolaryngology at the University of Texas Medical Branch in Galveston, Tex., between September, 1974, and May, 1975, 11 showed positive otologic and otoneurologic findings which are reported herein. One patient was surgically explored for an oval window fistula. In localizing and classifying these injuries, we have utilized extensive and broad-based test batteries, which include complete history, otologic and otoneurologic physical examination, audiometry, a central auditory test battery, and a vestibular test battery. These tests are described. The findings in each of the divers are illustrated and analyzed. This article further describes the use of these test batteries, which were employed to localize otoneurologic pathology in this sample of injured divers. Based on these cases, we have expanded and modified Edmonds' classification of the etiology of vertigo related to diving. We feel that the test batteries which we describe, or similar tests, should be part of the otologic and otoneurologic workup of injuries divers.

Effect of stable xenon inhalation on internal carotid artery blood flow in unanesthetized monkeys.

Stable xenon (Xe) gas, at inspired concentrations above 30%, reportedly increased cerebral blood flow (CBF) in animals and humans. An unpredictable Xe-induced elevation of CBF could result in erroneous CBF values being measured by Xe-enhanced computed tomography (Xe-CT). In order to detect a potentially rapid and transient effect of Xe on CBF, estimations of supratentorial CBF were obtained by Doppler flow probes chronically and bilaterally implanted on the internal carotid arteries of five adult monkeys. The unanesthetized monkeys with a clear plastic helmet were equilibrated for 15 min on a control gas (33% N2/67% O2) randomly exposed for 5 min to gas mixtures of either 33% Xe/67% O2 or 10% CO2/23% N2/67% O2. The mean control bilateral internal carotid artery blood flow (ICABF) was 23 +/- 10 ml/min (mean +/- SD), mean arterial pressure (MAP) was 101 +/- 13 mm Hg, and PaCO2 was 34 +/- 6 mm Hg. Inhalation of 33% Xe in O2 did not change the ICABF, MAP, or PaCO2. Inhalation of 10% CO2 in O2 increased the ICABF to 39 +/- 15 ml/min (p <0.001), MAP to 112 +/- 16 mm Hg (p <0.05), and PaCO2 to 54 +/- 5 mm Hg (p <0.001). The lack of change in ICABF and PaCO2 with 32% Xe inhalation suggests that a clinically relevant change in CBF is unlikely.

Neoglottic reconstruction after total laryngectomy: a preliminary report.

This paper is a preliminary report on neoglottic reconstruction of the larynx after total laryngectomy following the techniques described by Staffieri. Also included are general observations on the criteria for selecting candidates for this procedure. At the University of Texas Medical Branch in Galveston, this procedure has been attempted on eight candidates. Reconstruction was accomplished in six, of whom five achieved satisfactory speech, providing an 80% success rate. One of the five did not like the quality of his voice and refused to use it. The sixth produced speech with difficulty and is still undergoing speech therapy. One patient died from recurrence before a second stage could be carried out, and another patient did not have sufficient tissue for neoglottic reconstruction after total laryngectomy. Three patients developed salivary fistulas at the drain site, but all closed spontaneously with the application of pressure. From this data, one may conclude that this technique offers much potential and warrants further study.

Basilar artery migraine presenting as fluctuating hearing loss and vertigo.

A review of the literature on basilar artery migraine as well as a brief overview of classic migraine is given. Diagnosis and management are also discussed as well as six case histories.

Malignant external otitis. Cure with adjunctive hyperbaric oxygen therapy.

Malignant otitis externa developed in a 55-year-old man with diabetes. This Pseudomonas aeruginosa infection was refractory to high-dose moxalactam disodium therapy, despite sufficient in vitro tube dilution sensitivity results. When adjunctive hyperbaric oxygen therapy was added to the treatment regimen, the infection resolved.

Injury to the facial nerve associated with the use of a disposable nerve stimulator.

Clinical observations and experimental data from this study support the thesis that the disposable Weck nerve locator/stimulator may induce neural damage. This potential damage may cause at least a temporary paresis. Although more study is required to better document the method, degree, and factors influencing injury, we believe that enough evidence is present to induce caution and warrant further study. We recommend that the stimulators be used with caution on the lowest setting possible and with as little contact with the nerve as possible.

Utilization of a central auditory processing test battery in evaluating residual effects of decompression sickness.

Six professional divers were examined as patients who presented peripheral auditory, vestibular, or central symptoms attributed to incidents which occurred while diving. Each diver received a central auditory processing (CAP) test battery consisting of: (1) a dichotic sentence listening task, (2) a monotic filtered word task, (3) a binaural fusion task, and (4) an alternating speech task. The CAP test results, in all cases substantiated other neurological/vestibular test battery results which we have reported in detail previously.

Otoadmittance measurements in cases of dual ossicular disorders.

Audiologic evaluations, including otoadmittance measurements, were obtained on two patients, each of whom had dual, series-connected disorders of ossicular fixation and disarticulation. In one case, the disarticulation was the lateral-most disorder; in the other case the fixation was the lateral-most disorder. In both cases, it was the lateral-most disorder that had the dominant effect on the otoadmittance of the tympanic membrane, due to the fact that the sites of the two disorders were connected in series with the tympanic membrane.

Physiologic implications of adding small amounts of carbon dioxide to the gas mixture during inhalation of xenon.

In addition to being a physiologically active tracer of CBF, xenon (Xe) in subanesthetic concentrations produces a relatively mild lowering of carbon dioxide (CO2) in the blood and elevation of transcranial Doppler (TCD) velocity. The addition of small concentrations of CO2 (0.4-1.2%) to the inhaled mixture produced no measurable effect on end tidal (P(et)) CO2 or TCD velocity. Cerebral blood flow (CBF) alterations induced by Xe are minimized by allowing P(et)CO2 to fall, permitting quantitative measurement of CBF by the Xe/CT CBF method.

The protein kinase C inhibitor H-7, inhibits antigen and IL-2-induced proliferation of murine T cell lines.

Activation of protein kinase C has been shown to be involved in the activation pathway of many cell types. Recently, a number of investigations have suggested that protein kinase C plays an essential role in T lymphocyte activation. The recent synthesis of the protein kinase inhibitors, H-7 and HA1004, have now made possible a new approach for testing the relevance of protein kinase C in T cell activation and proliferation. We now report that the antigen-induced and interleukin-2-induced proliferation of murine T cell lines can be consistently inhibited by the protein kinase C inhibitor, H-7. HA1004, a somewhat more potent inhibitor of cyclic nucleotide-dependent protein kinases, but a significantly weaker inhibitor of protein kinase C than H-7, demonstrated no consistent inhibition of these T cell responses. These results represent a further demonstration that protein kinase C plays an essential role in the activation of T cells.