Heterogeneous enzyme immunoassay.

During the past 10 to 15 years immunoassays have gained acceptance as the methods of choice in the diagnosis of a number of disease states. At present the immunodiagnostic techniques employed range from radioimmunoassay for haptens through immunofluorescence for autoimmune diseases to complement fixation for viral infections. All of these assays have their own individual limitations such as: safety, short shelf life and sensitivity. The development of enzyme immunoassays, in particular enzyme linked immunosorbent assay (ELISA), has led to a substantial literature which offers the view that enzyme immunoassays provide a safe, sensitive and specific alternative to standard methods for the detection of antibodies or antigens. The application of heterogeneous enzyme linked immunosorbent assays for the quantitation of haptens, macromolecular antigens and antibodies is reviewed.

Multicenter audiometric results with the Vibrant Soundbridge, a semi-implantable hearing device for sensorineural hearing impairment.

The Vibrant Soundbridge, a semi-implantable hearing device for subjects with moderate to severe sensorineural hearing impairment was introduced commercially. First audiologic results are presented on 63 patients from 10 European implant centers. Hearing loss was at 0.5, 1, 2, and 4 kHz varying between 43 and 81 dB HL. The patients used the analogue audio processor, type 302. Measured sound-field gain was compared with NAL-R target values. For most patients an acceptable agreement was found. There was a subgroup of patients, however, with relatively low gain. The results suggest that this was related to the suboptimal positioning and fixation of the transducer to the incus.

Development of the Midland adult cochlear implant programme.

This paper describes the development of adult cochlear implantation in Birmingham over its first six years, from 1990 to 1996. During this time 366 patients were referred to the implant programme, female referrals outnumbered males 1.2:1. Eight per cent of referrals were over the age of 70. The annual rate of referral suggests a fairly steady demand for the service. Approximately one third of patients referred each year were subsequently implanted. The centre is currently performing an average of 2 implants per month. The average time from referral to implant is approximately 19 months. The greatest number of referrals originated from health districts closest to the implant centre. An examination of patients implanted suggested an imbalance in the uptake of the service amongst the different socio-economic groups.

Electrode complications in 100 adults with multichannel cochlear implants.

At switch-on (first post-operative stimulation of the implant) and during subsequent reprogramming, electrodes can, in some patients, be found to be non-functional or to be performing sub-optimally for a number of reasons. This paper examines the reasons for the poor performance of these electrodes by means of a retrospective analysis of 100 patient records. All of these patients received the Nucleus multichannel device. The most common reason for an electrode to require de-activation was found to be facial nerve stimulation, with poor sound quality and pain also being very common. Other reasons included absence of auditory stimulation, vibration, reduced dynamic range, throat sensations, absence of loudness growth or dizziness. The occurrence of these reasons along the electrode array was examined, more basal electrodes being found to be non-functional as a result of having a small dynamic range or poor sound quality. Pain and vibration were found to occur throughout the array and the more apical electrodes were found to be non-functional as a result of facial nerve stimulation. It is suggested that the electrodes at the basal end of the array are likely to be extra-cochlear or are at the site of the most cochlear damage, whereas the more apical electrodes lie in closer proximity to the facial nerve.

The Birmingham bone anchored hearing aid programme: referrals, selection, rehabilitation, philosophy and adult results.

The Birmingham bone anchored hearing aid team is part of the Birmingham osseointegrated programme. In the first seven years of its existence it has received 309 referrals. Twenty-six per cent had suffered a congenital conductive hearing loss and 74 per cent had an acquired conductive hearing loss; the majority secondary to chronic suppurative otitis media. This report is of 68 out of 106 adults wearing bone anchored hearing aids (BAHAs). Ninety-eight per cent showed audiological improvement with the congenital group demonstrating marginally the best free-field thresholds and speech discrimination. Questionnaire data as to the patient experience confirms the benefits especially hearing in noise, and comfort, and the vast majority were more satisfied with the bone anchored hearing aid than their previous aid.

The Birmingham bone anchored hearing aid programme: paediatric experience and results.

Over a five-year period, 34 patients have been referred to the Birmingham bone anchored hearing aid programme, paediatric section, of who 21 are now wearing the bone anchored hearing aid (BAHA) and four are awaiting surgery for fitting of the BAHA. Of the patients assessed, found to be suitable and who proceeded to surgery for the BAHA, 44 per cent had Treacher Collins syndrome, 28 per cent had bilateral atresia or microtia, 16 per cent had Goldenhaar's syndrome, four per cent (one patient) had branchio-otorenal syndrome and eight per cent had chronic suppurative otitis media. This paper presents objective and subjective data collected from these patients. It is shown that the BAHA is a very effective hearing aid for children with congenital hearing loss.

UCH/RNID single channel extracochlear implant: results in thirty profoundly deafened adults.

The University College Hospital/Royal National Institute for the Deaf (UCH/RNID) Cochlear Implant Programme has now given single channel extracochlear implants to forty profoundly deafened adults. Audiological, psychophysical, speech perceptual and subjective results for the first thirty cases are described. The main findings can be summarised as follows: 1. Users of the single channel extracochlear implant gained considerable improvements in their lipreading and communication ability, as assessed by both objective testing and by the patients' own reports. All acquired useful awareness of environmental sounds and an improvement in their quality of life; some also showed improvements in their own speech. A small number were capable of some open-set speech discrimination without lipreading. 2. Extracochlear implantation was not found to destroy residual hearing, although it did cause slight deterioration in hearing thresholds in some cases. 3. Our results so far suggest that patients deafened by meningitis are likely to obtain less benefit from a single channel cochlear implant than those deafened by other causes. Better results were also achieved by younger, more recently deafened patients and those who were good lipreaders. Despite the emergence of these trends we have not yet found a reliable way to predict benefit from an implant on the basis of preoperative variables. 4. Self-reported measures of the benefits of the implant correlated well with the objective test results, but also revealed important information that was not available from the objective tests. In particular, they showed that the improvement in lipreading provided by the implant was reduced in noisy conditions.

Outcomes from adult implantation, the first 100 patients.

We present the outcome of implantation in the first 100 adult patients treated under the Midland Cochlear Implant Programme. All patients were post-lingually deaf with profound or total hearing loss. Performance was tested in lip-reading, implant only and combined lip-reading and implant modes using BKB sentences, connected discourse tracking (CDT) and environmental sound recognition. Assessments were made at nine and 18 months post-implant. The dominant aetiologies were idiopathic and meningitis. Meningitis was associated with the greatest numbers of ossified cochleas. Forty-three per cent of cases of partial ossification were identified only at surgery. Four per cent of patients became non-users of their devices, however the majority used their implants for more than 12 hours each day. The mean scores at nine months post-implant, in the implant only mode, were for environmental sound recognition 56.7 per cent, for BKB sentences 46.6 per cent (80 per cent of patients scored above 0 per cent) and for CDT 31.2 words per minute (w.p.m.) (62 per cent scored above zero per cent). In the combined lip reading and implant mode the mean scores, at nine months, were for BKB sentences 81.5 per cent and for CDT 65.8 w.p.m. All results were sustained at 18 months. Patients reported that implantation significantly reduced their hearing handicap. Pre-operative measures of depression were also significantly reduced at nine months post-implant. Results were sustained at 18 months. Post-operative audiological outcomes in the electrical stimulation only mode correlated significantly with length of profound deafness. Results suggest that performance outcome is also related to the number of active electrodes.

Extra-cochlear implants: the patient's viewpoint.

A subjective questionnaire has been used for assessing cochlear implantees. It provides information on the benefits and the problems found after one year's use as viewed by the patients. This information is important to the management of future subjects for implantation. In three patients with a year's experience of implant use provision of environmental sound and improved speech loudness modulation were the most appreciated benefits. Improved speech reading ability did not emerge as the greatest benefit, except in one case in good listening conditions. Alleviation of tinnitus occurred only to a limited extent, in one patient out of the three.

Lipid-free glycerol teichoic acids with potent membrane-binding activity.

Lipid analysis of several glycerol teichoic acid preparations strongly indicated that covalently bound lipid is not required for spontaneous adsorption of glycerol teichoic acid to erythrocyte membranes. Although fatty acids were detected in each of four batches, none were covalently bound. Chloroform-ether-extracted antigens retained potent erythrocyte membrane-binding activity as measured by passive hemagglutination, even though they were shown to contain less than one fatty acid residue per 4,869 teichoic acid chains. Mild ammonolysis abolished erythrocyte-sensitizing activity in passive hemagglutination, but further studies indicated the loss of activity was due to partial destruction of the polyglycerophosphate backbone and not to the removal of esterified lipid. The amount of hydrolyzed antigen required to produce 100% passive hemagglutination inhibition was between 170 and 330 times the amount required to produce the same result using unhydrolyzed glycerol teichoic acid. The average chain length was reduced from 19.1 to 9.7, 7.4, and 5.1 glycerophosphate residues for antigen samples hydrolyzed for 1, 5, and 16 h, respectively.

Cross-reactions of Streptococcus mutans due to cell wall teichoic acid.

Antisera to the whole cells of Streptococcus mutans cross-reacted with antigen extracts from four other gram-positive species, as well as with those of three other oral streptococci. Similarly, antisera to these bacteria cross-reacted with extracts from S. mutans and with those from each other. Using a purified phenol extract of the walls of S. mutans, which was identified by chemical, immunochemical, and enzymatic analyses as glycerol teichoic acid, the cross-reactions were shown to be specific for a determinant of the teichoic acid backbone. Results were confirmed in immunodiffusion tests where clear bands of identify were shown. These observations point out the need for caution in sereological research empolying extracts of gram-positive bacteria and may be of interest in investigations of periodontal disease.

Preparation and chemical composition of the cell walls of Streptococcus mutans.

Purified cell walls from Streptococcus mutans strain BHT were prepared without the use of proteolytic enzymes in order to retain all cell wall constituents for chemical analysis. Of four methods employed, the Ribi cell fractionator produced disrupted cell suspensions which could be most thoroughly purified on sucrose gradients. Results of chemical analyses on purified cell walls prepared in this 8.9% glycerol teichoic acid, 33.6% non-peptidoglycan polysaccharide, and 49.9% peptidoglycan.

Modulation of the immune response to sheep erythrocytes by lipid-free glycerol teichoic acid.

The 4-day response of C3H/HeJ mice to sheep erythrocytes was suppressed by a lipid-free teichoic acid with an average molecular weight of 2,900 when it was administered by the intraperitoneal route. Enhancement was not observed at that time, and neither suppression nor enhancement could be demonstrated by the intravenous route. Either suppression or enhancement of background plaques could be induced, depending upon the timing. Dosage influenced the degree of suppression from 8 to 100 micrograms, whereas suppression of background plaques required only 1 microgram of lipid-free teichoic acid. The kinetics of the sheep erythrocyte response was altered by treatment of the mice with lipid-free teichoic acid, delaying the peak until day 5 and producing enhancement at that time. Although lipid-free teichoic acid was shown to be toxic for mouse splenocytes (50% lethal dose, ca. 200 micrograms) in vitro, no effect at the levels employed was observed in vivo. The data presented indicate that modulatory activity is influenced by route, timing, dosage, and apparently the number of antibody-secreting cells.

Immunogenicity of soluble versus cellular glycerol teichoic acid.

Guinea pigs which were injected with either whole bacilli or purified soluble glycerol teichoic acid (GTA) usually exhibited a rise in hemolysin titer to GTA-coated erythrocytes. The only exceptions were those animals having high baseline titers of natural anti-GTA antibodies. Rats yielded better responses than guinea pigs and produced significantly higher responses to the soluble antigen than to the cellular GTA. Rats reared on a GTA-free diet were predominantly free of natural antibodies to GTA and furnished a more clear-cut model for assaying immune responses. Using this model, it was shown that adsorption of GTA to homologous erythrocytes before injection resulted in poor responses, suggesting that such spontaneous adsorption does not account for the good responses to soluble antigen. In GTA-deprived rats, positive skin tests were induced only with bacilli, whereas migration inhibitory factor was induced with both bacilli and soluble antigen. Hemolytic plaques in immunized rats were increased over controls with both kinds of immunogen, but the GTA-deprived rats responded better than conventional ones, and hemolytic plaque responses to bacilli were better than those to soluble antigen. This reversal of the serum hemolysin results may be due to delayed suppression by soluble GTA or to antibody cycling. The guinea pig data, combined with results from GTA-deprived rats, suggest that high antibody levels resulted in depressed antibody synthesis, perhaps because antibody cycling was initiated. No evidence was found to explain the superior responses to soluble antigen, but it did not seem related to formation of immune complexes or adsorption to erythrocyte membranes.

The UCH/RNID cochlear implant programme: patient selection.

After an initial postal questionnaire, patients undergo a series of tests and assessments designed to establish their suitability for implantation. The following criteria should be met: Total or profound post-lingual hearing loss. Sufficient age to give informed consent. General good health. Psychological stability. Unable to benefit from hearing aids. Free from middle ear or mastoid disease. Detailed medical, audiometric, vestibular and psychological investigations are performed, as well as acute electrical stimulation of the cochlea, and a hearing aid trial in those subjects with some measurable hearing. Fifty-two applicants have so far been assessed and of these 14 have been found to be suitable for implantation and seven have received implants.

A clinical study of tinnitus maskers.

This report describes a three-centre study of the effectiveness of tinnitus maskers, combination instruments (masker plus hearing aid), and hearing aids in the management of tinnitus. Some 472 patients entered the study with 382 reaching the first evaluation session after a minimum period of 6 months from fitting, and 206 reaching the second evaluation not less than 6 months after the first. The study included two control groups, by which to assess the comparative benefit to be derived solely from the investigation and counselling of such patients. The principal results were as follows: thorough investigation and careful counselling do much to help the patient; much further benefit is given by tinnitus masking instruments of various kinds; maskers are more often effective than hearing aids, although the latter are frequently the most appropriate first treatment of those patients who have substantial (but not yet treated or insufficiently treated) hearing difficulties as well; there is no evidence of masking having any harmful effect on hearing. None of the audiometric or tinnitus tests currently employed can be regarded as predictive, either of tinnitus severity, or of the eventual outcome of masking therapy, however certain measurements may help as a guide to patient management.