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Biomedical subjects

J A McClure

Publications and source records attributed to J A McClure.

At least 19 recordsLinked to original sources

A cure for benign positional vertigo.

Benign positional vertigo is a common clinical entity encountered in any dizzy clinic. It is easily diagnosed on the basis of historical information and a positive Dix-Hallpike position test. The available evidence suggests that this condition is due to involvement of the posterior semicircular canal. The pathophysiology of this condition can be explained theoretically on the basis of free-floating particles within the endolymph of the posterior semicircular canal that move under the influence of gravity with certain provocative positional changes. Based on this theoretical model, a variety of particle-repositioning manoeuvres have been developed that attempt to relocate the loose particles from the posterior semicircular canal to the utricular sac. If the particles are kept in the utricular sac for a period of 48 h by maintaining the patient in an upright position, the clinical symptoms are relieved in a high proportion of patients. If the manoeuvre is unsuccessful on a first attempt, or if the benign positional vertigo recurs at a later date, the condition can usually be relieved by a second manoeuvre. Bilateral benign positional vertigo can be treated by performing a manoeuvre on one side followed by a manoeuvre on the other side at a later date. On occasion, posterior canal benign positional vertigo is converted to horizontal canal benign positional vertigo, but this subsides readily within the 48-h post-manoeuvre period.

Humans↗

Phosphorylation-associated conformation shift of anti-oncogene phosphoprotein p53 in concanavalin-A activated human T lymphocytes.

A new radioimmunoassay for p53, employing an anti-peptide antibody directed against conserved Domain V, exhibited specificity for a relatively dephosphorylated form of p53. This form, correlated with the monoclonal antibody PAB421+ conformation, appeared transiently in the cytosol of cycloheximide-treated T cells undergoing activation by concanavalin-A/serum. Concurrently, there were decreased levels of p53 in the nucleus that correlated with increased phosphorylation of p53. After 90 min nuclear levels of p53 increased steadily above levels of unstimulated cells. Anti-p53 antibodies introduced into cells prior to stimulation enhanced cell proliferation in response to mitogens.

Alkaline Phosphatase↗

Free-floating endolymph particles: a new operative finding during posterior semicircular canal occlusion.

Most clinicians accept cupulolithiasis as the pathophysiological mechanism underlying benign paroxysmal positional vertigo (BPPV.) According to this theory, a cupular deposit induces a gravitational effect on the posterior canal crista. Posterior semicircular canal occlusion is a new operative procedure for treating incapacitating BPPV. It is postulated that canal occlusion abolishes endolymph movement within the canal, effectively fixing the cupula and rendering it unresponsive to both angular and linear acceleration (gravity). During two recent canal occlusions, abundant "free-floating particles" were identified within the posterior canal endolymph. When changing the position of the canal in the earth vertical plane, these free-floating particles would move under the influence of gravity. The hydrodynamic drag of the particles would induce endolymph movement with cupular displacement leading to the typical response. This finding supports an alternate explanation to cupulolithiasis as the pathophysiological mechanism underlying BPPV.

Aged↗

Posterior semicircular canal occlusion in the normal hearing ear.

This report outlines our experience with posterior semicircular canal occlusion, a new operative procedure for intractable benign paroxysmal positional vertigo (BPPV). We postulate that the resulting solid canal "plug" prevents endolymph movement within the posterior canal, which effectively fixes the cupula. This selectively abolishes the receptivity of the posterior canal to both angular acceleration and gravity without influencing the other inner ear receptors. We previously reported the success of this procedure in two patients with BPPV and a co-existing profound sensorineural hearing loss in the affected ear. Since that report, a slightly modified technique has been used to occlude six more posterior canals--five in normal hearing ears. While our follow-up times range from only 3 to 18 months, all eight patients continue to be relieved of their BPPV. Temporary mixed hearing losses occurred in three of the five ears with normal preoperative hearing. Hearing in all five patients ultimately returned to the preoperative state. We believe this procedure is a simpler and safer alternative to singular neurectomy for the treatment of intractable benign paroxysmal positional vertigo.

Aged↗

Posterior semicircular canal occlusion for intractable benign paroxysmal positional vertigo.

Benign paroxysmal positional vertigo (BPPV) is most often a self-limited disorder arising from the posterior semicircular canal of the undermost ear in the Hallpike position. Some individuals with this disorder have severe and protracted symptoms requiring more than expectant therapy. We describe two patients with intractable BPPV and profound sensorineural hearing loss in the affected ear treated by transmastoid posterior semicircular canal occlusion. Postoperatively, both were relieved of their BPPV and demonstrated preserved lateral semicircular canal function as measured by electronystagmography. We feel this new procedure provides a simpler and possibly safer alternative to singular neurectomy and should be given future consideration in the treatment of intractable BPPV in a normal-hearing ear.

Adult↗

Rotatory recovery nystagmus: an important localizing sign in endolymphatic hydrops.

Localizing the ear responsible for vertigo attacks may be exceedingly difficult in patients with delayed endolymphatic hydrops, vestibular Ménière's disease or bilateral Ménière's disease. This has important clinical implications when planning operative treatment. We present a case of delayed endolymphatic hydrops to exemplify these difficulties and demonstrate the localizing value of recovery nystagmus. We stress the importance when possible of monitoring patients with endolymphatic hydrops for recovery nystagmus during acute vertigo attacks. Monitoring should include direct eye observation as pure rotatory nystagmus escapes detection on electronystagmography.

Aged↗

The membrane rupture theory of Menière's disease--is it valid?

The Membrane Rupture Theory states that the acute attack of Menière's disease occurs when endolymph, with its high potassium ion concentration, escapes into the perilymph and surrounds the first-order neuron. Initially, this causes partial depolarization of the nerve and an increased resting discharge, followed by complete depolarization. Clinically, one would expect an initial irritative nystagmus (toward the affected side) followed by a paralytic nystagmus (toward the unaffected side). To confirm this, the guinea pig perilymphatic space was perfused with an artificial endolymph solution. The results confirmed an irritative/paralytic sequence of nystagmus that differs from the pattern of spontaneous nystagmus observed with ENG monitoring during the acute attack of Menière's disease. Early in the attack, one observes a paralytic nystagmus followed by a secondary nystagmus beating toward the affected side (similar to an irritative nystagmus) as the patient recovers. This raises questions about the validity of the Membrane Rupture Theory.

Animals↗

Vertigo and imbalance in the elderly.

The diagnosis of vestibular disorders causing dizziness and imbalance in the elderly can present a difficult problem. Knowledgeable diagnosis depends on an understanding of the role of the vestibular end-organs as motion sensors and sensors of gravity as well as an understanding of how the vestibular system influences body balance and how visual mechanisms interact with the vestibular system. Based on a knowledge of these physiological principles, a number of interesting aspects of age-related vestibular disorders are discussed in more detail.

Adaptation, Physiological↗

Immunological characterization of phosphoprotein phosphatases.

Phosphoprotein phosphatases regulate the biological activities of proteins through their involvement in cyclic phosphorylation/dephosphorylation cascades. A variety of multimeric phosphatases have been isolated and grouped into several classes, termed type 1 and types 2A, 2B, and 2C. To elucidate the relationship between the different phosphoprotein phosphatases, highly purified enzymes from soil amoebae, turkey gizzards, bovine heart and brain, and rabbit skeletal muscle and reticulocytes were tested for immunological antigenic relatedness. Two heterologous antibody preparations were employed for this purpose. One was made against an Acanthamoeba type 2A phosphatase and the other was made to bovine brain phosphatase type 2B (calcineurin, holoenzyme). Specific subunit cross-reactivity was examined by protein blot ("Western") analysis. The antibody to the type 2A phosphatase reacted with the catalytic subunits of every type 2 enzyme tested, including both the catalytic and Ca2+-binding subunits of the Ca2+/calmodulin-dependent type 2B phosphatase (calcineurin), bovine cardiac type 2A phosphatase, and turkey gizzard smooth muscle phosphatase-1 (type 2A1). It did not react with any type 1 phosphatase (catalytic subunit or ATP-Mg-dependent). The antigenic relatedness of calcineurin and the bovine cardiac type 2A phosphatase (Mr 38,000) was demonstrated further by protein blot analysis showing that the anti-calcineurin antibody cross-reacted with both enzymes. The mutual cross-reactivity poses an intriguing problem because these enzymes are so different in their molecular structures and modes of regulation. The degree of evolutionary conservation exhibited by the antigenic cross-reactivity of the type 2 enzymes from a broad range of species and tissues suggests a strong selective pressure on maintaining one or more features of these important regulatory enzymes.

Animals↗

Horizontal canal BPV.

Benign paroxysmal vertigo (BPV) is generally attributed to a differential density condition in the posterior semicircular canal. Although the posterior canal is implicated because of its dependent position, the possibility exists that either the horizontal or superior canal could become involved. This paper reports on seven patients with a clinical picture consistent with horizontal canal BPV. The characteristic features are brief vertigo and horizontal nystagmus precipitated by head movement into or out of one of the lateral positions. Position change toward the left lateral position induces left beating nystagmus and vice versa for position change toward the right. The direction of the nystagmus indicates a utriculopetal "endolymph flow" when the affected horizontal canal is undermost. This could be explained by particle movement or a "viscous plug" in the posterior aspect of the canal.

Adult↗

Effect on brainstem auditory evoked responses of posterior semicircular canal occlusion in guinea pigs.

The site of origin of benign paroxysmal positional vertigo is the posterior semicircular canal and when persistent, the condition is known as cupulolithiasis. Singular neurectomy is the current procedure of choice for the treatment of incapacitating cupulolithiasis. The neurectomy is difficult to learn and carries a significant risk of hearing loss. An alternative procedure, whereby the posterior canal is occluded, is discussed. This was performed on 11 guinea pigs and the effect on hearing was measured using brainstem evoked audiometry. Eight animals showed no hearing loss while the other three had a mild to moderate loss of hearing due to intra-operative complications. The effect of canal plugging on hearing compares favorably with the hearing results obtained with singular neurectomy. Posterior semicircular canal occlusion is suggested as a safer and technically easier treatment for incapacitating cupulolithiasis.

Animals↗

Orbital Burkitt's lymphoma in a homosexual man with acquired immune deficiency.

A 22-year-old homosexual man had persistent systemic lymphadenopathy and a three-week history of rapid swelling and induration of his right upper eyelid. Acquired immune deficiency leading to the development of lymphoma was suspected. A biopsy specimen of the mass revealed Burkitt's lymphoma and treatment with systemic chemotherapy and radiation therapy resulted in remission. A significant number of patients with acquired immune deficiency are developing Burkitt's lymphoma. The three separate syndromes of acquired immune deficiency and their associated ophthalmic manifestations are discussed.

Acquired Immunodeficiency Syndrome↗

Purification of a protein phosphatase from Acanthamoeba that dephosphorylates and activates myosin II.

The actin-activated ATPase activity of myosin II from Acanthamoeba castellanii is inhibited by phosphorylation of 3 serine residues near the carboxyl end of the heavy chain of the molecule. We have purified a protein phosphatase from Acanthamoeba using myosin II as a substrate. This phosphatase has a molecular weight of 39,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and an isoelectric point in urea of 5.2. The enzyme also is active against other phosphoserine protein substrates such as turkey gizzard smooth muscle myosin light chain, but not against a synthetic phosphotyrosine protein substrate. It does not hydrolyze ATP or p-nitrophenol phosphate. No effector has been found to increase substantially the activity of the enzyme as isolated, but it is inhibited by ATP, pyrophosphate, and NaF. This inhibition is reduced in the presence of MnCl2. The Mg2+-dependent actin-activated ATPase of myosin II is activated by dephosphorylation of phosphorylated myosin II by the phosphatase. Its broad substrate specificity, molecular weight, and response to protein phosphatase inhibitors suggest that the Acanthamoeba protein phosphatase is a type 2A phosphatase (Cohen, P. (1982) Nature (Lond.) 206, 613-620).

Actins↗

Vestibular asymmetry. Some theoretical and practical considerations.

Pathological vestibular asymmetry can be divided into static and dynamic types. Static asymmetry results from a unilateral change of the resting neural input. Acute, chronic, and recovery stages can be recognized if one interprets the direction and intensity of the resultant spontaneous nystagmus relative to the clinical picture. Static asymmetry is additive with induced asymmetry and manifests itself as directional preponderance or as the direction-fixed or direction-changing feature of positional nystagmus. Dynamic asymmetry refers to abnormal asymmetry induced by normal head movements. For example, with unilateral hypofunction, a greater gain is observed with head movement toward the unaffected side, suggesting nonlinearity as specified by Eswald's second law. Visually induced vestibular asymmetry is a form of dynamic asymmetry generated by convergence of visual-vestibular information, and causing symptoms in certain "motion-active" visual environments.

Eye Movements↗

Diazepam as an anti-motion sickness drug.

Diazepam has been used empirically for the relief of vertigo and, in addition, there are animal studies to suggest that this drug suppresses the vestibular system. One might anticipate therefore that diazepam would be an effective antimotion sickness drug. To study this, motion sickness was generated in four groups of normal subjects by having the subject make controlled head movements while rotating at constant velocity. Every subject was subjected (using a double-blind technique) to four different drug states, namely no drug, placebo, dimenhydrinate, and diazepam. Each group of subjects received the drug state at a different time interval (i.e. 30, 60, 90, and 120 min) prior to the motion sickness exposure. Motion sickness endpoints were measured subjectively using a nausea scale and objectively using a sweat sensor. The results showed significant antimotion sickness properties for both dimenhydrinate and diazepam as compared to the placebo. For the time intervals studied, the maximum effect was obtained at 120 min for both drugs.

Adolescent↗

Recovery nystagmus in Ménière's disease.

Spontaneous nystagmus occurs during a Meniere's attack although the literature indicates that the direction can be variable. Previous observations made during the acute and recovery stages of a Meniere's attack suggested that the direction of the spontaneous nystagmus was consistent with the primary-secondary sequence of nystagmus that occurs with relatively prolonged stimulation of the normal vestibulo-oculomotor system. To evaluate this nystagmus pattern further, spontaneous nystagmus was monitored in eight patients using DC electronystagmography during an acute Meniere's attack. All showed an initial contralateral nystagmus during the acute phase of the attack with reversal to an ipsilateral (or recovery) nystagmus, as the acute symptoms subsided. Such a pattern of nystagmus occurring over a few hours is a helpful diagnostic aid, and when surgery is being considered, it provides objective evidence of the ear with active disease.

Adult↗