Episodic vestibular disruption following ablation of the inferior olive in rats: behavioral correlates.

The experiments herein investigate whether the behavioral responses to transient and episodic vestibular disruption and permanent ablation are distinct in the absence of climbing fiber input. Subjects in group 1 received an IP injection of PBS followed by an IP injection of niacinamide. Seven days later these rats received the first of 3 serial transtympanic injections of TTX on the same side with 7 days between each injection. Following each TTX injection rats displayed unilateral vestibular symptoms that persisted beyond 48h. Spontaneous barrel rolling behavior was not observed. Group 2 subjects received an IP injection of 3-acetylpyridine (3-AP)+niacinamide followed by the same TTX regimen as group 1. Following each TTX injection vestibular symptoms (severe body twisting and persistent spontaneous barrel rolling) emerged rapidly (<15min) and resolved by 72h. Group 3 subjects received an IP injection of 3-AP+niacinamide and 7 days later a single unilateral transtympanic injection of sodium arsanilate. Rats in group 3 developed vestibular symptoms similar to those observed in group 2 although there was no resolution of these symptoms. The results indicate that TTX has a rapid rate of infiltration and blockade of the VIIIth nerve that persists for >48h and then completely resolves. The contrast in vestibular symptoms between groups 1 and 2 suggest that climbing fibers are recruited soon after onset of vestibular disruption and play a role in attenuating the severity of vestibular symptoms associated with transient/episodic vestibular disruption.

Ultrastructure and synaptology of the paratrigeminal nucleus in the rat: primary pharyngeal and laryngeal afferent projections.

The paratrigeminal nucleus (PTN) receives primary afferent projections from the aerodigestive tract and orofacial regions and plays a role in the integration of visceral and somatic information. This study describes the fine structure of the rat PTN and the synaptology of primary afferent projections from the pharynx and larynx. Injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) or cholera toxin-HRP (CT-HRP) were made into the wall of the pharynx or larynx to label primary afferent axon terminals. Light microscopic observations demonstrated that afferent axons terminated bilaterally in overlapping fields in the PTN. Electron microscopic observations of the PTN revealed that there were three distinct classes of neurons, based on morphology and axosomatic contacts. The most abundant neurons, Type 1, were fusiform in shape and received very few or no axosomatic contacts. Type 2 neurons contained prominent Nissl substance (rough endoplasmic reticulum) and few axosomatic contacts, while Type 3 neurons had many axosomatic synapses. Terminals containing round, clear vesicles and forming asymmetric contacts (round asymmetric, RA) with dendrites were the predominant synaptic type in the PTN. Primary afferent terminals from the pharynx and larynx were of the RA type and formed synaptic contacts with small-diameter (<1 microm) dendrites. Visceral primary afferent inputs from the pharynx and larynx overlap with trigeminal somatic afferents in the PTN and have similar synaptic morphology. The results support the concept that the PTN provides an anatomical substrate for mediating viscerovisceral and somatovisceral reflexes via efferent connections with autonomic centers in the brainstem.

Status of complementary and alternative medicine in the osteopathic medical school curriculum.

Reflecting society's interest in complementary and alternative medicine (CAM), most allopathic medical schools in the United States offer instruction in CAM. Pertinent information about the teaching of CAM at osteopathic medical schools is lacking. The authors therefore sought to document the form and content of CAM instruction at osteopathic medical schools and compare their findings with those reported for allopathic medical schools in a recently published survey. Phone conversations with academic officials at each of the 19 colleges of osteopathic medicine revealed that only one school did not teach CAM. With the help of these officials, the authors identified 25 CAM instructors at 18 osteopathic medical schools and sent them questionnaires. All returned a completed form with details about CAM instruction at their schools. The authors found that CAM material was usually presented in required courses sponsored by clinical departments, was most likely taught in the first 2 years of medical school, and involved fewer than 20 contact hours of instruction. The topics most often taught were acupuncture (68%), herbs and botanicals (68%), spirituality (56%), dietary therapy (52%), and homeopathy (48%). Most (72%) CAM instructors were also practitioners of CAM modes of therapy. Few (12%) of the instructors taught CAM from an evidence-based perspective. The authors conclude that the form and content of CAM instruction at osteopathic medical schools is similar to that offered at allopathic medical schools and that both osteopathic and allopathic medical schools should strive to teach CAM with less advocacy and more reliance on evidence-based medicine.

Episodic blockade of cranial nerve VIII provokes asymmetric changes in lobule X of the rat.

Although debilitating syndromes like Ménière's disease are in part characterized by recurrent or episodic vestibular disturbance the study of episodic vestibular disruption has only recently been possible with the introduction of a new model utilizing tetrodotoxin (TTX). In the present study, serial unilateral transtympanic administration of TTX produced behavioral symptoms indicative of transient vestibular disruption and novel patterns of Fos activity in the brainstem and cerebellum. Following two or three serial injections of TTX and a final survival time of 2 h, Fos immunocytochemistry revealed a distinct pattern of labeling in the brainstem that differed temporally from that observed following a single unilateral TTX injection. Specifically there was protracted expression of Fos in the beta subdivision of the inferior olive (IO) on the side ipsilateral to TTX treatment. In the cerebellum, the hallmark of episodic vestibular blockade was an asymmetric pattern of Fos labeling that involved all three layers of the cortex. In particular, there was prominent Fos labeling of Purkinje cells in the contra-TTX half of lobule X. In view of the fact that Fos labeling is not found in Purkinje cells following a single transient event or following peripheral vestibular ablation, it is suggested that Fos expression in Purkinje cells is a unique feature of episodic vestibular disruption and may represent a novel plastic response by a select population of Purkinje cells to episodic functional deafferentation.

Asymmetric Fos labeling in lobule X of the cerebellum following transtympanic tetrodotoxin (TTX) in the rat.

Unilateral transtympanic administration of the sodium channel blocker tetrodotoxin (75 microl of 3 mM TTX in 0.1 M citrate buffer, pH 5.0) produced behavioral symptoms indicative of unilateral vestibular disruption. Following survival times of 2 and 24 h immunocytochemistry for Fos revealed asymmetric labeling in the granular and molecular layers of lobule X of the cerebellum and in the medial cerebellar nucleus. The granular and molecular layers as well as the medial cerebellar nucleus ipsilateral to TTX treatment contained elevated levels of Fos relative to the same regions contralaterally and when compared to controls receiving equal volume injections of vehicle. The asymmetric changes in neuronal activity as measured by Fos (genetic activity) in lobule X implicate this region of the vestibulocerebellum in recovery from transient vestibular disruption in the intact system.

Distribution of Fos labeling in the inferior olive following transient blockade of the VIIIth cranial nerve.

The sodium channel blocker, tetrodotoxin (TTX), is an effective tool for blockade of action potentials in neurons. Unilateral transtympanic administration of 3 mM TTX produced behavioral symptoms paralleling those previously reported following unilateral vestibular ablation. Behavioral symptoms were evident as early as 15 min post-TTX. Fos immunocytochemistry revealed an initial bilateral distribution of Fos in the inferior olive (IO) followed by an almost exclusively unilateral distribution of Fos. By 1 h, Fos was predominantly localized in subdivisions of the IO contralateral to TTX treatment. Fos labeling in the IO was most pronounced at 2- and 6-h survival times and was localized in the contralateral IOA, IOB, IOC, IOBe, and IOK subdivisions and bilaterally in the IOM and IODM. Other regions of the brainstem including the vestibular nuclei, prepositus hypoglossi, dorsal paragigantocellular reticular nucleus, nucleus of the tractus solitarius and locus coeruleus also exhibited altered patterns of Fos labeling following TTX. The finding that Fos activity in the IO is initially bilateral and then rapidly becomes unilateral has not been reported for the traditional vestibular ablation models and may be unique to the TTX model. In addition, since altered Fos activity is readily detected in the IO at time-points prior to detectable changes in Fos in the central vestibular complex it is possible that the IO is particularly sensitive to events precipitated by unilateral vestibular disturbance.

The teaching of complementary and alternative medicine in U.S. medical schools: a survey of course directors.

PURPOSE: The number of U.S. medical schools offering courses in complementary and alternative medicine (CAM) has risen sharply in recent years. This study gauged the current state of CAM instruction by gathering details about the specific topics being taught and the objectives behind the instruction. METHOD: Data were collected from questionnaires mailed to 123 CAM course directors at 74 U.S. medical schools. RESULTS: Questionnaires were returned by 73 course directors at 53 schools. The topics most often being taught were acupuncture (76.7%), herbs and botanicals (69.9%), meditation and relaxation (65.8%), spirituality/faith/prayer (64.4%), chiropractic (60.3%), homeopathy (57.5%), and nutrition and diets (50.7%). The amounts of instructional time devoted to individual CAM topics varied widely, but most received about two contact hours. The "typical" CAM course was sponsored by a clinical department as an elective, was most likely to be taught in the first or fourth year of medical school, and had fewer than 20 contact hours of instruction. Most of the courses (78.1%) were taught by individuals identified as being CAM practitioners or prescribes of CAM therapies. Few of the courses (17.8%) emphasized a scientific approach to the evaluation of CAM effectiveness. CONCLUSION: A wide variety of topics are being taught in U.S. medical schools under the umbrella of CAM. For the most part, the instruction appears to be founded on the assumption that unconventional therapies are effective, but little scientific evidence is offered. This approach is questionable, especially since mainstream medicine owes much of its success to a foundation of established scientific principles.