Large-scale purification and preliminary x-ray diffraction studies of human aspartylglucosaminidase

Selective vestibular neurectomy is an effective treatment for intractable vertigo of peripheral vestibular origin when preservation of hearing is a goal. The retrolabyrinthine and retrosigmoid-intracanalicular approaches have been used predominantly at our institutions over the last 10 years. The results and complications of these two techniques were compared. No significant differences were found between hearing results in these two patient groups. The retrosigmoid-internal auditory can approach yielded better control of recurrent episodic vertigo, as well as superior ablation of postoperative ice-water caloric responses (p < 0.05). Surgical complications, including the incidence of cerebrospinal fluid leakage (greater in retrolabyrinthine approach) and postoperative headache (more prevalent in retrosigmoid approach), were also analyzed. To further evaluate the results of this study, data were reanalyzed and compared with previously published reports of selective vestibular nerve section.     

Vestibular nerve section: long-term follow-up

Vestibular nerve section is considered an effective modality in the treatment of refractory and incapacitating vertigo. Typically nerve section results are described on the basis of short-term follow-up. We have reviewed 41 cases of vestibular nerve section spanning an 18-year period. Although the majority of cases involved classic Meniere's disease, delayed endolymphatic hydrops, vestibular neuritis, and Meniere's syndrome secondary to head trauma were also included. Surgical approaches included translabyrinthine (20 cases), retrolabyrinthine (14 cases), retrosigmoid (six cases), and middle fossa (one case) procedures. Postoperative follow-up time averaged 102 months, with 46% of patients followed for a minimum of 9 years. Results are reported according to standards set forth by the American Academy of Otolaryngology--Head and Neck Surgery. Vertigo was cured or markedly improved in 88% of cases (90% in patients with Meniere's disease) at 18 to 24 months postoperatively. These vertigo results were sustained at the time of latest follow-up. Functional level was also preserved over time despite the development of bilateral symptoms in several cases. The rate of bilateral disease reached 22% of cases. Although vertigo results remained stable, long-term follow-up of successful hearing preservation cases demonstrated deterioration over time. Postoperative continuation of medical treatment is urged to optimize and sustain the vestibular neurectomy result.     

Trigeminal neuralgia: retrolabyrinthine selective posterior root section

Experience gained from the treatment of 41 patients with 42 operations for the relief of Vth nerve pain over the past 5 years is reported. For the selective section of the posterior root of the trigeminal nerve 28 retrolabyrinthine procedures were performed for typical tic douloureux with complete lasting relief in 25; 1 was relieved with the addition of aspirin; and 2 were relieved by Tegratol even though it was ineffective before surgery. There were no deaths and no serious complications. None had facial paralysis or anesthesia dolorosa. The retrolabyrinthine approach to the posterior root of the trigeminal nerve is ideally suited for those patients with refractory tic douloureux or patients with facial pain secondary to other causes such as tumor. Because of its effectiveness and low morbidity, this procedure offers advantages over other surgical techniques.     

Middle ear pressure and dysfunction of the labyrinth: is there a relationship?

Relationships between middle ear pressure and non-infection-related cochleovestibular dysfunction have been suggested by several authors. According to some data, vertiginous attacks can be prevented by the insertion of a ventilation tube in patients suffering from Meniere's syndrome. The aim of our study was to investigate if the incidence of eustachian tube malfunction and pathologic middle ear pressure is frequent, and if routine implantation of ventilation tubes is reasonable in ears with dysfunctions of the labyrinth, including clinical Meniere's syndrome. So, we determined in our pressure chamber all active and passive parameters of eustachian tube function in 40 patients suffering from Meniere's syndrome, sudden sensory hearing impairment (SSHI), or vestibular neuronitis. Our results disclosed no nonrandom incidence of impaired tubal function among our patients compared to healthy control subjects. Pressure equalization was sufficient in most patients suffering from clinical Meniere's syndrome, and only one patient with vestibular neuronitis presented with a patulous tube. Our results show that impairment of vestibular or cochlear function is not regularly accompanied by eustachian tube dysfunction. Furthermore, no patient reported symptoms while pressure variation was performed. We conclude that variation of middle ear pressure does not usually play a role in the genesis of Meniere's syndrome, vestibular neuronitis, or SSHI. Thus, from our data, we cannot recommend routine implantation of tympanic ventilation tubes in patients suffering from Meniere's syndrome, vestibular neuronitis, or sudden hearing loss.     

Human vestibular schwannoma growth in the nude mouse: evaluation of a modified subcutaneous implantation model

HYPOTHESIS: Based on the hypothesis that vestibular schwannomas can be successfully implanted and grown in the nude mouse model, an in vivo experiment was designed for subcutaneous implantation of solid vestibular schwannoma tissue. BACKGROUND: Vestibular schwannomas are benign tumors arising from Schwann cells of cranial nerve VIII. Little in vivo research has been carried out with these tumors, due in part to the difficulty to grow cells in culture or maintain tumor in an animal model. Recently, vestibular schwannomas have been implanted in nude mice with moderate success. The current study evaluates a modification of prior techniques in an effort to establish a dependable research model. METHODS: Thirty-six nude mice were implanted with variable-sized vestibular schwannoma tissue from three human subjects. Volumes implanted ranged from 14-170 mm3. Mice were observed for 28 days and individual volumes recalculated. Eleven of the mice were observed for a total of 56 days with volumes re-evaluated, and tumors subsequently were removed for assessment of viability and vascularity. RESULTS: At 28 days, 36 tumors (100%) showed take with 34 tumors (94%) showing macroscopic growth. The 11 tumors observed for 56 days showed a trend of stable or decreased size at 56 days compared with that of the 28-day measurement. Overall growth from time of implantation to measurements at 56 days was noted in 8 (73%) of 11 tumors when measured at the skin and in 10 (91%) of 11 tumors when direct tumor volume was measured. One hundred percent of tumors evaluated microscopically at 56 days was viable. All tumors at the time of removal had significant vascularity with a mean of 70.68% (SD = 23.42) of surface covered with vessels. There were no significant differences in take and growth for the larger tumor specimens compared with those of smaller sizes. CONCLUSION: Human vestibular schwannomas successfully can be implanted and maintained in the subcutaneous pocket of the nude mouse. This in vivo tumor model provides a reliable, accessible base for further research with vestibular schwannomas.     

Establishing a community network for recruitment of African Americans into a clinical trial. The African-American antiplatelet stroke Prevention Study (AAASPS) experience

A major aspect of a clinical trial is the ability to successfully recruit patients. There is a paucity of information concerning the nuances of recruiting study patients, especially those from minority communities. As minorities generally have been underrepresented in the health-care system, they may be less likely to participate in clinical trials or other studies. Thus, a strategy is needed to overcome this potential shortfall. One of our solutions has been the development of a community network to help disseminate information about our program. We believe that a key aspect has been the involvement of community members during pre-trial planning, community awareness programs, and our Community Advisory Panel. We also believe that it may be a major error to bring a health-care initiative unannounced into a targeted community without extensive pre-program planning in cooperation with that community. As our community awareness scheme suggests (Figure), there are many possible avenues to heighten awareness about a health-care program. While the church remains an important institution for religious and cultural activities in the African-American community, we have found that the news, television, and radio media also can be a powerful source for spreading awareness. Thus, we recommend creating awareness about an initiative through a "grassroots" approach of church and community organizations, along with a global approach through news, television, and radio media. As part of the awareness promotion campaign, it must be emphasized that the study is safe and provides benefits to enrollees. The success of health programs is largely dependent on community acceptance, which must be established in the pre-program planning stages of the initiative. This concept of obtaining community approval and acceptance prior to program initiation is not a new one, nor does it exclusively apply to the African-American community. Community leaders and members need to have a vested interest in such a program and a sense of empowerment. Through this type of communication, patient enrollment and community satisfaction can be substantial. Such success can serve as a springboard for other targeted health-care studies or programs in high-risk communities.     

Occupational disease and injury and state compensation

A vestibular neurectomy is indicated in all cases of persistent vertigo without central vestibular compensation, with or without hearing loss. The retrosigmoid approach is described, as well as the postoperative results in 12 patients. The results are compared with those of other surgical treatments.     

Motion sickness susceptibility correlates with otolith- and canal-ocular reflexes

Since motion sickness (MS) never occurs in individuals who lack functional vestibular apparatus, it has been suggested that MS susceptible individuals have more sensitive vestibular systems than non-susceptible people. However, previous investigations involving only stimulation of the semi-circular canals have been inconclusive. We measured gain and time constant (TC) of horizontal canal-ocular reflex (COR) and magnitude of otolith-ocular reflex (OOR). We found that MS susceptibility was not correlated to COR gain but was negatively correlated to OOR magnitude. Thus, MS susceptible individuals do not have more sensitive vestibular systems. We also found a positive correlation between MS susceptibility and TC. We hypothesize that central vestibular integration (velocity storage mechanism), by increasing low frequency vestibular inputs, would favour MS.     

Retrieval of specimens in laparoscopy using reclosable zipper-type plastic bags: a simple, cheap, and useful method

In this study we evaluated the usefulness of a new bilayer artificial dermis (TERUDERMIS; Terumo Corporation, Japan) for vestibular extension. It is composed of a collagen sponge with the silicone layer which is sloughed off as the mucous membrane heals. We have used it for vestibular extension in 50 patients. The material was effective in nearly all patients in promoting haemostasis, relieving pain, inducing granulation, promoting rapid epithelialization, and preventing contracture. There were no side-effects. The greatest problem with such materials in the past has been contracture at the vestibular extension area. However, we found that the degree of contracture was similar to that seen with autogenous mucosa or free skin graft. Our results indicate that the material might be useful for vestibular extension.     

Mutations in the COCH gene are a frequent cause of autosomal dominant progressive cochleo-vestibular dysfunction, but not of Meniere's disease

The COCH gene is the only gene identified in man that causes autosomal dominantly inherited hearing loss associated with vestibular dysfunction. The condition is rare and only five mutations have been reported worldwide. All affected families showed a similar progressive hearing loss and vestibular dysfunction. Since Meniere's disease-like symptoms have also been described in some families, it was suggested that COCH mutations might be present in some patients diagnosed with Meniere's disease. In this study, using a Japanese population, we performed a COCH mutation analysis in 23 patients from independent families with autosomal dominant hearing impairment, four of whom reported vestibular symptoms, and also in 20 Meniere's patients. While a new point mutation, A119 T, was found in a patient with autosomal dominant hearing loss and vestibular symptoms, no mutations were found in the Meniere's patients. Like all other previously identified COCH mutations, the mutation identified here is a missense mutation located in the FCH domain of the protein. The current mutation is located in close spatial proximity to W117, in which a mutation (W117R) had previously been associated with autosomal dominant hearing loss. Model building suggests that, like the W117R mutation, the A119 T mutation does not affect the structural integrity of the FCH domain, but may interfere with the interaction with a yet unknown binding partner. We conclude that mutations in the COCH gene are responsible for a significant fraction of patients with autosomal dominantly inherited hearing loss accompanied by vestibular symptoms, but not for dominant hearing loss without vestibular dysfunction, or sporadic Meniere's disease.     

Vestibular control of the cardiovascular system

Due to modern living conditions the human cardiovascular system is frequently exposed to rapid or/and prolonged changes in gravitational forces. These transients are very short compared to the timescale of the evolution causing substantial difficulties in adaptation. As it has been many times proven experimentally since the first observation in 1922, the vestibular system affects directly the regulation of the cardiovascular system. For example, bilateral transsection of the vestibular nerve of cats significantly disturbs the compensation of acute hypotension induced by lowering the animal's head. The results of human studies also indicate the existence of vestibulo-sympathetic reflexes. Vestibular excitation caused by caloric to other stimuli results in increased sympathetic efferent activity. Several groups or nuclei in the brain-stem (medial vestibular ncl., subretrofacial ncl., the lateral area of tegmentum) were confirmed to have important mediatory function in the central organization of the vestibulo-sympathetic reflex. However, the role of vestibular system in long-term adaptive responses of the vascular system of chronic changes in body position is not classified yet. Such a possible role is suggested by our experimental findings during the last decade. Electronmicroscopic examinations indicated that two-week long orthostatic load due to head-up tilting changes significantly and differently the innervation density of blood vessels in the extremities of rats. There also have been a significant amplification of acute myogenic response to intraluminar pressure-elevation in the saphenous vein. We suppose that adrenergic mechanisms under vestibular control are at least in part responsible for the regionally different adaptive changes including structural remodelling. Spectral analysis of the arterial blood pressure suggested that a two week-long orthostatic load can already alter the overall control of the cardiovascular system in rats.     

Working with difficult-to-treat eating disorders using an integration of twelve-step and traditional psychotherapies

In summary, we have a multidimensional treatment program that attempts to integrate psychodynamic, cognitive-behavioral, systemic, psychopharmacologic, and 12-step interventions. For patients who have not had previous treatments or patients who are young adolescents, we do not emphasize the 12-step approach. For our difficult-to-treat patients, our current overall impression is that the benefits of adding the 12-step component have outweighed the costs. We began the program with an expressed intent of experimenting with the integration. Staff were subsequently recruited who were open to the experiment and the success of the integration has been a function of the flexibility within the staff. Our hunch is that this integration would not work as well with an existing staff who harbored prejudice toward either position. Actually, we have found working on the integration quite invigorating. Our recovering counselors have raised issues that we have not heard raised in the more traditional settings we have been associated with. Likewise, we have seen our counselors grow professionally from hearing alternative views of why individuals struggle and how they get better. The exchange has been synergistic rather than divisive. Although we are encouraged by our early experience, it is the long-term outcome that will clarify the relative usefulness of this treatment strategy. We are confident that as we live with the integration longer, more of the advantages and disadvantages will become apparent and perhaps we can refine our understanding of which subgroup of patients makes most use of this type of integrated approach.     

Recent advances in the pharmacology of the vestibulo-ocular reflex system

Recent advances in the pharmacology of the vestibulo-ocular reflex have had a major impact on our understanding of the vestibular system, the sensory system primarily concerned with the stabilization of gaze and posture during head movement. Increasing evidence suggests that afferent transmission from the receptor hair cells in the vestibular labyrinth to the vestibular nerve probably involves glutamate acting on a number of excitatory amino acid receptor subtypes. Furthermore, hair-cell sensitivity appears to be regulated by cholinergic, GABA-mediated and, possibly, peptide-mediated efferent feedback from the CNS. Likewise, it seems clear that an excitatory amino acid, probably glutamate, is the major transmitter used by the vestibular nerve in its synapses with neurones of the brainstem vestibular nucleus. In this review, Paul Smith and Cynthia Darlington discuss the large number of receptor subtypes that have been identified in the vestibular nucleus, including receptors for several peptides that may have a role in co-transmission.     

Hallucinations, sleep fragmentation, and altered dream phenomena in Parkinson''s disease

Middle ear effusion has been considered the most common cause of vestibular disturbance in children. However, there have been only a few studies on vestibular disturbance in children with otitis media with effusion. We studied the vestibular systems of 30 children with otitis media with effusion aged 8 to 13 years and compared the results with 15 age- and sex-matched controls. A questionnaire relating to vestibular disturbance was given to patients and their parents. Spontaneous nystagmus and positional nystagmus were recorded by electronystagmography as diagnostic tests of the vestibular system. Romberg's and past-pointing tests were performed on children with otitis media with effusion and controls. After vestibular tests were completed, myringotomy was performed, and a ventilation tube was inserted. The questionnaire and the vestibular tests were repeated after the operation and during the first month after surgery. Our study showed that there was a history of vestibular disturbance in 33% of children with otitis media with effusion. Electronystagmography and Romberg's test findings demonstrated that 33% of the children had vestibular dysfunction (p < 0.05). After myringotomy with ventilation tube insertion, vestibular test results returned to normal, and symptoms related to vestibular disturbance improved. These findings confirm the assumption that middle ear effusion may affect the vestibular system, which can be resolved after myringotomy with ventilation tube insertion.     

Activation of the hippocampal formation by vestibular stimulation: a functional magnetic resonance imaging study

Functional MRI (f-MRI) is a non-invasive technique developed to permit functional mapping of the brain with a better temporal and spatial resolution than that offered by PET techniques. In our study, f-MRI was performed using blood oxygenation level dependent (BOLD) contrast imaging based on the magnetic properties of hemoglobin. This method relies on changes in the blood supply to the brain that accompany sensory stimulation or changes in cognitive state. All the images were obtained at 1.5 T on a Signa GEMS without ultrafast imaging. The vestibular stimulation was cold irrigation of the external auditory meatus (caloric stimulation). A population of normal healthy volunteers without a history of vestibular dysfunction was studied. The hippocampal formation as well as the retrosplenial cortex and the subiculum were activated by vestibular stimulation, suggesting that this activation may be related to spatial disorientation and a sensation of self-rotation experienced by the subjects during vestibular stimulation. The other results are similar to those obtained using PET.     

Vestibular-evoked electromyographic responses in soleus: a comparison between click and galvanic stimulation

The aim of this study was to demonstrate, if possible, vestibulospinal reflex responses in soleus using a stimulus known to be capable of exciting vestibular afferents, namely 100-dB (NHL) clicks. We were able to show short-latency electromyographic (EMG) responses after clicks in five of eight normal subjects, and then we compared these responses with those after transmastoid galvanic stimulation (12 normal subjects). Stimulation of the side towards which the head was rotated (i.e. the side facing backwards) with either clicks or the cathode (anode applied to the opposite side) gave an initial excitatory response in soleus, while click or cathodal stimulation of the opposite side (i.e. the side facing forwards) gave an initial inhibitory response. Onset latencies and modulation with changes in postural task were identical for both click- and galvanic-evoked responses. In addition, there was a significant correlation between the amplitudes of the responses in soleus after click and galvanic stimulation (R2=0.72). These similarities suggest that the earliest reflex responses in soleus after clicks and galvanic stimulation may be mediated by a common central pathway. In contrast, there was no correlation between the amplitudes of responses evoked by 100-dB clicks in soleus and those evoked by the same stimulus in the sternocleidomastoid. We conclude that vestibular activation by clicks can evoke reflex responses in lower-limb muscles and these responses have similar characteristics to the earliest responses evoked by galvanic vestibular stimulation.     

Partial cricotracheal resection with primary anastomosis in the pediatric age group

The traditional approach to severe subglottic stenosis (SGS) in the pediatric age group is laryngotracheal reconstruction (LTR). This approach may be complex and multistaged, with variable and unpredictable success rates in the individual patient. Excellent results have been reported in adults who had severe SGS and underwent partial resection of the cricoid and primary thyrotracheal anastomosis. This procedure has not been widely reported in infants and children. We report our experience with this procedure in 16 pediatric patients with grade III or IV SGS. Eleven patients had multiple previous LTR operations. The preoperative evaluation, surgical techniques, postoperative care, complications, and final results are described and discussed. Fourteen patients were decannulated after the procedure, 1 patient needed a second open procedure prior to decannulation, and 1 patient with concomitant bronchopulmonary dysplasia remains cannulated, for an overall 94% decannulation rate. Fourteen patients have no limitation of respiration, and 1 patient has moderate exercise intolerance. The results of this series suggest that partial cricotracheal resection with primary anastomosis is a relatively safe and effective procedure for pediatric patients with severe SGS.     

The spotty sign

BACKGROUND: This report details our experience in 13 patients with a technical modification of the standard central shunt. METHODS: The study was performed using a retrospective chart review approach. In our operation, the aorto-Gore-Tex (W.L. Gore & Assoc, Flagstaff, AZ) anastomosis is created in a side-to-side fashion with the free end of the Gore-Tex shunt being oversewn. RESULTS: All patients had echocardiographic evidence of shunt patency in the immediate postoperative period, and there have been no cases of late shunt occlusion at a mean follow-up period of 10 months. CONCLUSIONS: We believe this approach will yield patency rates equivalent to or better than those of the standard central shunt. The technique has the advantage of creating a short, straight-lying shunt that is less likely to kink or be injured on repeated sternotomy and in which flow may be more reliable.     

Germ-line mutations in the neurofibromatosis 2 gene: correlations with disease severity and retinal abnormalities

Neurofibromatosis 2 (NF2) features bilateral vestibular schwannomas, other benign neural tumors, and cataracts. Patients in some families develop many tumors at an early age and have rapid clinical progression, whereas in other families, patients may not have symptoms until much later and vestibular schwannomas may be the only tumors. The NF2 gene has been cloned from chromosome 22q; most identified germ-line mutations result in a truncated protein and severe NF2. To look for additional mutations and clinical correlations, we used SSCP analysis to screen DNA from 32 unrelated patients. We identified 20 different mutations in 21 patients (66%): 10 nonsense mutations, 2 frameshifts, 7 splice-site mutations, and 1 large in-frame deletion. Clinical information on 47 patients from the 21 families included ages at onset and at diagnosis, numbers of meningiomas, spinal and skin tumors, and presence of cataracts and retinal abnormalities. We compared clinical findings in patients with nonsense or frameshift mutations to those with splice-site mutations. When each patient was considered as an independent random event, the two groups differed (P < or = .05) for nearly every variable. Patients with nonsense or frameshift mutations were younger at onset and at diagnosis and had a higher frequency and mean number of tumors, supporting the correlation between nonsense and frameshift mutations and severe NF2. When each family was considered as an independent random event, statistically significant differences between the two groups were observed only for mean ages at onset and at diagnosis. A larger data set is needed to resolve these discrepancies. We observed retinal hamartomas and/or epiretinal membranes in nine patients from five families with four different nonsense mutations. This finding, which may represent a new genotype-phenotype correlation, merits further study.     

Endolymphatic sac tumors: report of three cases

OBJECTIVE AND IMPORTANCE: We present three cases of endolymphatic sac tumors and review the previously published cases. Despite frequent extension to the cerebellopontine angle, these rare tumors have only recently been recognized by neurosurgeons. CLINICAL PRESENTATION: A 26-year-old man developed a progressive hearing loss, revealing an intrapetrous retrolabyrinthine tumor on the right side. A 28-year-old woman experienced a left cerebellopontine angle syndrome, with a lytic intrapetrous mass extending into the cerebellopontine angle. A 38-year-old woman presented with an intracranial hypertension syndrome caused by a tumor of the jugular foramen. INTERVENTION: For the first and second patients, the tumors originated from the operculum of the endolymphatic sac. Total removal was achieved, via a transpetrosal approach, in these two cases. No recurrence was detected after a 20-month follow-up period. For the third patient, the tumor originated from the distal part of the sac. Recurrence was observed 8 years after subtotal removal via a retrosigmoid route. Histological analysis revealed a papillary-cystic adenocarcinomatous pattern in all cases, without features of aggressiveness. CONCLUSION: Endolymphatic sac tumors are locally invasive neoplasms characterized by bipolar intrapetrous and posterior fossa involvement. The anatomic complexity of the endolymphatic sac may explain the distinct patterns of extension of these tumors. Early radical surgery is related to good outcomes.