Effects of oral propafenone on defibrillation and pacing thresholds in patients receiving implantable cardioverter-defibrillators. Propafenone Defibrillation Threshold Investigators.

OBJECTIVES: The effects of propafenone, a predominantly class IC antiarrhythmic drug, on defibrillation and pacing thresholds were evaluated in patients undergoing cardioverter-defibrillator implantation. BACKGROUND: Previous studies have shown that the class IC agents encainide and flecainide may increase the energy requirements for pacing and defibrillation. Animal studies with propafenone have shown inconsistent results regarding its effect on defibrillation energy requirements. This report investigated the effects of propafenone on defibrillation and pacing thresholds in humans. METHODS: After cardioverter-defibrillator implantation, 47 patients were enrolled in a double-blind, three-way parallel, randomized trial of 450 mg/day (Group 1) or 675 mg/day (Group 2) of oral propafenone or placebo (Group 3) for 3 to 7 days. Predischarge defibrillation and pacing thresholds after treatment were compared with baseline thresholds obtained at implantation. RESULTS: There was no statistically significant difference between implantation and predischarge defibrillation thresholds in the three groups (Group 1: [mean +/- SE] 11.0 +/- 1.3 vs. 12.1 +/- 1.5 J; Group 2: 11.5 +/- 1.1 vs. 13.6 +/- 1.3 J; Group 3: 12.5 +/- 1.2 vs. 13.3 +/- 1.6 J), and no significant difference between treatment groups was found with a 0.86 power to detect a 5-J difference between groups. Paired pulse width pacing thresholds at 2.8 V were compared in 14 patients. A small increase of 0.02 ms was noted at predischarge testing in patients treated with propafenone and placebo. CONCLUSIONS: Short-term oral propafenone (450 and 675 mg/day) does not significantly affect defibrillation or pacing thresholds. Concomitant use of propafenone in patients with implantable cardioverter-defibrillators with recurrent ventricular or atrial tachyarrhythmias should not interfere with proper device function.

Cerebral blindness and encephalopathy with cyclosporin A toxicity.

We observed acute cerebral blindness and encephalopathy complicating cyclosporin A (CyA) toxicity in a 5-year-old transplantation patient. Serum CyA level was 1,704 ng/ml (normal, less than 300 ng/ml). Additional neurologic complications of CyA toxicity will be reviewed.

Quantitative autoradiography of 5-[3H]6-cyano-7-nitro-quinoxaline-2,3-dione and (+)-3-[3H]dizocilpine maleate binding in rat vestibular nuclear complex after unilateral deafferentation, with comparison to cochlear nucleus.

The distributions of non-N-methyl-D-aspartate and N-methyl-D-aspartate receptors in the rat vestibular nuclear complex were estimated by quantitative autoradiography of 5-[3H]6-cyano-7-nitro-quinoxaline-2,3-dione and (+)-3-[3H]dizocilpine maleate binding, respectively. The binding of 5-[3H]6-cyano-7-nitro-quinoxaline-2,3-dione in the vestibular nuclear complex was also compared with that in the cerebellar cortex and cochlear nucleus. Measurements were made in control rats and in rats with unilateral destruction of the inner ear and removal of the vestibular ganglion. Compared to the unlesioned side, 5-[3H]6-cyano-7-nitro-quinoxaline-2,3-dione binding in the lesioned-side vestibular nuclear complex was decreased significantly in all regions at two to four postoperative days. However, the bilateral asymmetry disappeared in most regions by 30 days. 5-[3H]6-Cyano-7-nitro-quinoxaline-2,3-dione binding increased in the molecular layer of the cerebellar cortex at 30 days after lesion, although there were no clear changes at two to seven days. 5-[3H]6-Cyano-7-nitro-quinoxaline-2,3-dione binding in the cochlear nucleus decreased on the lesioned side, compared to the unlesioned side, in regions receiving significant auditory nerve innervation, but increased in the molecular layer of the dorsal cochlear nucleus. (+)-3-[3H]Dizocilpine maleate binding in regions of the vestibular nuclear complex was reduced on the lesioned side, compared to the unlesioned side, after deafferentation, with the largest reductions usually at 30 postoperative days. It is suggested that: (i) non-N-methyl-D-aspartate receptors are involved in synaptic transmission for both vestibular and auditory nerve fibers, while the involvement of N-methyl-D-aspartate receptors is less certain; (ii) unilateral deafferentation of the vestibular nuclear complex can result in bilateral asymmetries for non-N-methyl-D-aspartate and N-methyl-D-aspartate receptors, which are most prominent at earlier and later survival times, respectively; and (iii) vestibular compensation may involve regulation of both non-N-methyl-D-aspartate and N-methyl-D-aspartate receptors in the vestibular nuclear complex and activation of non-N-methyl-D-aspartate receptor-related processes in cerebellar cortex.

Myasthenia gravis with thymoma and pure red blood cell aplasia.

A case of myasthenia gravis with histopathologic confirmation of spindle cell thymoma and pure red blood cell aplasia is reported. This is the twelfth case in the literature in which a simultaneous occurrence of all three disorders, with documented thymic pathology, is noted. Immunologic observations in this patient include an elevated acetylcholine receptor antibody and antinuclear antibody titer, agglutination of mouse red blood cells when combined with the patient's serum, and lack of inhibition of binding of radioactive erythropoietin to mouse red cell receptors when combined with the patient's serum. Although both myasthenia with thymoma and pure red blood cell aplasia may have a common immunologic denominator, our findings in this case indicate that inhibition of erythropoiesis is unrelated to erythropoietin receptor blockade. An alternative hypothesis is offered based on defective T-cell function.

Parathyroid gland transplantation after total thyroidectomy with pharyngolaryngoesophagectomy.

Surgical treatment of extensive hypopharyngeal carcinoma often includes total thyroidectomy together with resection of the primary disease. The risk of removing or damaging the parathyroid glands is considerable; this may render the patient permanently hypoparathyroid with all the problems of management. These patients must be on lifelong supplementation and at times, due to failure to take the medication, hypocalcemic crises are precipitated. To avoid this problem, we have been identifying the parathyroid glands intraoperatively and, after pathological confirmation, have transplanted them to the forearm. Three patients who underwent this procedure are presented. All are normocalcemic without supplementation and parathyroid hormone assays on serum from the transplanted forearm show significantly elevated levels.

Comparison of surgeries for removal of primary vestibular inputs: a combined anatomical and behavioral study in rats.

Unilateral removal of Scarpa's ganglion and neurectomy of the peripheral vestibular nerve branches were compared in rats as methods to eliminate primary vestibular input. Ocular nystagmus was consistently observed after both types of lesion, but it completely disappeared within 4 to 7 days. Imbalance and rotation were more serious and prolonged after ganglionectomy than after peripheral neurectomy. Corresponding with these differences in symptoms were differences in terminal degeneration. After ganglionectomy, degenerated axons and terminals were distributed throughout all terminal regions of primary vestibular fibers on the lesioned side, while after peripheral neurectomy, the degeneration was more limited. The results of this study suggest that vestibular ganglionectomy is a more successful approach than peripheral vestibular neurectomy for removing the primary vestibular input.

Otolaryngologic management of dizziness in the older patient.

Studies report that dizziness is the most common presenting symptom in older patients who seek primary care. To understand the causes of dizziness, which is one of the major risk factors in causing falls in the older population, basic anatomy and physiology are reviewed in this article. Age-specific histopathologic changes occur in the labyrinth of the inner ear. To display evidence of the patient's symptoms, evaluation must include a comprehensive history, neurotologic examination, and diagnostic testing. There are common disorders associated with dizziness; thus, management depends on the cause. Once a diagnosis is secured, treatment is instituted based on sound medical principles.

Tinnitus: etiology and management.

Tinnitus is the perceived sensation of sound in the absence of acoustic stimulation. Individuals who suffer from it are commonly between the ages of 40 and 80 years. Tinnitus is often classified as objective or subjective, yet the pathophysiologic cause is still unknown. Subjective tinnitus is largely identified with hearing loss. Management of tinnitus is based on an individual approach; there is no single treatment or regimen for it.

Head-upright tilt-table testing: a useful tool in the evaluation and management of recurrent vertigo of unknown origin associated with near-syncope or syncope.

Recurrent idiopathic vertigo associated with near-syncope and syncope is a common perplexing problem, some cases of which are considered autonomically mediated (vasovagal). Upright-tilt-table testing has emerged as a potential method to test for vasovagal episodes. This study evaluated the use of this technique in the evaluation and management of patients with recurrent idiopathic vertigo associated with near-syncope or syncope. Twenty-one patients with recurrent unexplained vertigo and syncope/near-syncope and 11 control subjects were evaluated by use of an upright-tilt-table test for 30 minutes, with or without a graded isoproterenol infusion (1 to 4 micrograms/min given intravenously), in an attempt to provoke hypotension, bradycardia, or both, which reproduced the patient's symptoms. The patients included 10 men and 11 women (mean age, 51 +/- 16 years). Eleven controls with no history of vertigo were also studied. Transcranial Doppler sonography was used to assess cerebral arteriolar blood flow during tilt. All tilt-positive patients were placed on therapy with either beta-blockers, disopyramide, or transdermal scopolamine, the effectiveness of which was determined with another tilt-table study. Symptoms occurred in seven patients (33%) during the baseline tilt and in eight patients (38%) during isoproterenol infusion (total positives, 71%). Transcranial Doppler sonography demonstrated a 225% +/- 192% increase in pulsatility index and a 70% +/- 29% increase in resistance index (indicative of cerebral arteriolar vasoconstriction) at the time of vertigo. No control subject experienced syncope during this test. Each tilt-positive patient eventually became tilt-negative with therapy, and over a mean follow-up period of 26 months, no further episodes have occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Enzymes of transmitter and energy metabolism in cat middle ear muscles.

Activities of the enzymes choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), which metabolize the neuromuscular transmitter acetylcholine, and malate and lactate dehydrogenase (MDH and LDH), enzymes of oxidative and glycolytic energy metabolism, respectively, were measured in the middle ear muscles of the cat. For comparison, the same enzyme activities were measured in extraocular muscle tissue and in three hindlimb muscles rich in either slow oxidative (soleus), fast glycolytic (white part of vastus lateralis), or fast oxidative glycolytic (plantaris) muscle fibers. ChAT and AChE activities were much higher in middle ear muscles than in hindlimb muscles, consistent with a denser neuromuscular innervation, as in extraocular muscles. By contrast, MDH and LDH activities were remarkably low in the middle ear muscles, lower than in any of the hindlimb muscles or the extraocular muscles. Denervation of the stapedius muscle by peripheral transection of the facial nerve resulted in decreases in all four enzyme activities without associated changes in the tensor tympani. Surgical ablation of the peripheral facial nerve supply to the stapedius muscle appears to be a feasible option for producing its denervation. The results suggest some rather specialized chemical characteristics for the middle ear muscles.

Astrocyte reaction in the rat vestibular nuclei after unilateral removal of Scarpa's ganglion.

Unilateral vestibular ganglionectomy (UVG) results in a complete degeneration of vestibular nerve fibers and terminals in the ipsilateral vestibular nuclear complex (VNC). A subsequent glial reaction may affect the activities of VNC neurons and thereby influence compensation for lesion-induced vestibular disorders. Expression of glial fibrillary acidic protein (GFAP), a specific marker for reactive astrocytes, was demonstrated immunohistochemically in the rat VNC at 7, 14, and 35 days after UVG. An increased GFAP-positive astrocytic response was evident at 7 days after lesion in all the VNC regions on the lesioned side and in some regions on the unlesioned side and remained through 35 days. The glial response included hypertrophy, which was more prominent at 7 days than at 14 days or 35 days, and proliferation, more prominent at the later times, of GFAP-positive astrocytes. Astrocytic projections around VNC neuron somata and proximal dendrites increased in number and became thicker and more elongated, especially at 14 days, in the lateral vestibular nucleus. It is suggested that UVG results in a bilateral astrocytic reaction in the VNC that would affect the subsequent compensation.

Vestibulo-thalamic projections studied with antidromic technique in the cat.

The vestibulo-thalamic projection was investigated in anaesthetized cats. Electrical stimulation of posterolateral thalamic areas frequently changed the spontaneous firing pattern of neurons in the vestibular nuclei but only 5% were antidromically invaded. This group was further analysed with regard to types of labyrinthine and somatosensory input; thalamo-projecting neurons in the vestibular nuclei are frequently located in the lateral vestibular nucleus, they receive no monosynaptic inflow from the labyrinth and they often receive convergent vestibular and somatosensory input.

Limb input to the cat vestibular nuclei.

The input from fore- and hindlimbs to the vestibular nuclear complex (VNC) was investigated in awake cats. Electrical stimulus was given to the sciatic, radial and vestibular nerves bilaterally and single unit responses were recorded in the VNC with extracellular technique. The position of the microelectrode was histologically confirmed. All four major vestibular nuclei received fore- as well as hindlimb input. Forty per cent of the neurons with limb input also received vestibular afferents. No major distinguishing features appeared between the different nuclei with regard to response characteristics. Certain differences in laterality of response, quantitative fore-hindlimb ratio and somatosensory-labyrinthine convergence were observed however. Response latencies to sciatic and radial nerve stimuli always exceeded a 3 msec and were grouped around 8 and 16 msec. A third population of vestibular neurons had latencies over 20 msec. Both excitatory and inhibitory responses were recorded, with the latter not always following an activation. The findings illustrate the complex nature of the ascending pathway to the VNC and the integrative properties of this complex.

Labyrinthine input to the vestibular nuclei of the awake cat.

The labyrinthine input to the vestibular nuclei was investigated in 24 awake cats. Stimulus consisted of electrical shocks given through bipolar silver wire electrodes, implanted in the utricular and lateral ampullar nerves. Throughout the vestibular nuclei, single units were recorded extracellularly with glass micropipettes filled with Fast Green. The tracts of the penetrating electrodes were identified histologically. In all four nuclei units responding to both labyrinths outnumbered unilaterally responding neurones with certain differences between the individual nuclei. Excitatory as well as inhibitory responses were observed, polysynaptic being more common than mono- or disynaptic ones. No monosynaptic contralateral responses were seen. The latency distribution of contralateral responses closely mirrored that of ipsilateral responses within each nucleus. Both excitatory and inhibitory responses fell into relatively segregated populations, based upon latency distribution. This implies separate pathways for labyrinthine input to the vestibular nuclei.

Labyrinthine and somatosensory convergence upon vestibulospinal neurons.

In awake cats cells forming the lateral (LVST) and medial (MVST) vestibulospinal tracts were identified by employing antidromic stimulation of the spinal cord. Neuronal responses to bilateral vestibular, forelimb, hindlimb, and neck electrical nerve stimulation were analysed. Extracellular recording in the vestibular nuclei was performed via a glass micropipette saturated with Fast Green, to aid in later histological tract identification. The number of cells projecting to cervical and lumbar regions in the dorsal and ventral division of Deiters' nucleus did not differ significantly. An unexpectedly large number of MVST units was found in the descending nucleus. Some MVST units projected to the lumbar cord but in both the medial and descending nuclei, projections to the cervical cord were in majority. Almost all spinal projecting vestibular neurons received labyrinthine input and more than half received somatosensory input. The units could be separated into several populations on basis of excitatory and inhibitory labyrinthine response latencies indicating multiple pathways. As regards labyrinthine-somatosensory integration the two tracts were found to be quite similar. The extent and complexity of labyrinthine-somatosensory convergence indicate the importance of feed-back mechanisms upon postural controls also at the level of the vestibular nuclei.

Labyrinthine and somatosensory convergence upon vestibulo-ocular units.

The vestibular nuclei were investigated in 18 adult cats. Vestibulo-oculo-motor neurons were identified by antidromic stimulation of the ascending medial longitudinal fasciculus (MLF). The neurons were subjected to various stimuli: vestibular, neck, forelimb and hindlimb nerve stimulation on both sides. The recording was extracellular with micropipettes containing Fast Green. Only the medial and the superior vestibular nuclei were found to project to the MLF. All projecting units had input from the labyrinths. Excitatory response latencies to ipsilateral labyrinth stimulation never exceeded 3 msec. Both excitatory and inhibitory response latencies could be distributed into different categories. The majority of the neurons did not receive a somatosensory input, and surprisingly few convergent units could be seen. Peripheral somatosensory information apparently plays a minor role in vestibulo-ocular relations.

Quantitative distribution of amino acids in the rat vestibular nuclei.

The normal concentrations of 12 amino acids in the vestibular nuclei of rats were quantitatively measured using microdissection of freeze-dried brain sections combined with high performance liquid chromatography (HPLC) analysis. Both excitatory amino acids, aspartate and glutamate, showed only small variation across the vestibular nuclei. The distribution of glutamine tended to parallel that of glutamate. The inhibitory amino acids, gamma-aminobutyrate (GABA) and glycine, were much more concentrated in some regions than in others. GABA tended to be more concentrated than glycine in dorsal and rostral nuclei, while glycine tended to be more concentrated than GABA in ventral and caudal nuclei. The distribution of taurine was comparable to that of GABA, suggesting a close relationship with GABA function. Asparagine, serine, threonine, arginine, alanine and tyrosine had relatively low concentrations without significant differences among vestibular nuclei. Our results suggest that (1) different parts of the vestibular nuclear complex may receive similar amounts of excitatory amino acid afferents, (2) there is predominance of GABA or glycine as an inhibitory transmitter in different parts of the vestibular nuclear complex, and (3) there may be a close functional relationship between taurine and GABA within the vestibular nuclear complex. These results provide data basic to further research on the details of amino acid functions in the normal and abnormal vestibular system, as well as studies of plasticity in this system.

Near-drowning, scuba diving: an unusual late sequela of bulbar polio.

This case report illustrates an unusual hazard of underwater sports: vagal neuropathology secondary to early poliomyelitis which resulted in residual palato-pharyngeal paresis. Gag and swallowing reflexes appeared to function adequately but in fact were not normal. When stressed, during water aspiration, they were inadequate, resulting in great risk to the underwater enthusiast. A history of early viral myelitis must be considered as a potential hazard in underwater sports.

Hearing under stress: II. Effect of hyperventilation and hypercapnia on speech discrimination.

Changes in the ability to discriminate speech from a eucapnic state to hyperventilation and hypercapnia were investigated. Standard speech audiometric techniques were employed to determine the speech reception threshold and the speech discrimination values, while respiratory conditions were varied and measured utilizing a mixed-gas breathing method. Respiratory parameters were similar to those encountered in aircraft personnel who experience oxygen/pressure system malfunction. The results of the study suggest no significant change in the speech reception threshold while in a hyperventilated or hypercapnic state. The speech discrimination results, however, suggest a significant performance decrement while in a state of hyperventilation.

Hearing under stress: IV. a speech delivery communication system for utilization in high ambient noise environments.

Many communication systems have been devised to improve the individual's ability to receive speech information in the presence of ambient noise. The purpose of this study was to determine the effectiveness of a speech delivery system which combined a high degree of ambient noise attenuation with the ear's own natural amplification phenomenon--the occlusion effect. It was demonstrated that occlusion of the auditory system at the level of the external auditory meatus, in conjuction with bone-conducted speech stimuli presented at the mastoid, was most effective in providing high speech discrimination ability with significant attenuation of ambient noise.