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We investigated 34 deaf and hard-of-hearing children with hearing devices aged 8-12 years and 30 typical hearing peers. We used the capability approach to assess well-being in both groups through interviews. Capability is "the real freedom people have to do and to be what they have reason to value." Speech perception, phonology, and receptive vocabulary data of the deaf and hard-of-hearing children, that were used retrospectively, showed a large variability. The analysis of the relation between clinical quantitative outcome measures and qualitative capability interview outcomes suggests that at this age, differences in clinical performance do not appear to translate into considerable differences in capability, including capability did offer insight into the factors that appeared to ensure this equivalence of capability. We argue that capability outcomes should be used to determine the focus of (auditory) rehabilitation and support, in line with the United Nations Convention on the Rights of the Child., (© The Author(s) 2023. Published by Oxford University Press.)

Objectives: We aimed to determine whether children with severe hearing loss (HL) who use hearing aids (HAs) may experience added value in the perception of speech, language development, and executive function (EF) compared to children who are hard of hearing (HH) or children who are deaf and who use cochlear implants (CIs) and would benefit from CIs over HAs. The results contribute to the ongoing debate concerning CI criteria. We addressed the following research question to achieve this aim: Do children who are HH or deaf with CIs perform better than children with severe HL with HAs with respect to auditory speech perception, and receptive vocabulary and/or EF?, Design: We compared two groups of children with severe HL, profound HL or deafness, with CIs or HAs, matched for gender, test age (range, 8 to 15 years), socioeconomic status, and nonverbal intelligence quotient. Forty-three children had CIs (pure-tone average at 2000 and 4000 Hz >85 dB HL), and 27 children had HAs (mean pure-tone average: 69 dB HL). We measured speech perception at the conversational level (65 dB SPL) and the soft speech perception level (45 dB SPL). We established receptive vocabulary using the Peabody Picture Vocabulary Test-III-NL. We tested EF using the Delis Kaplan Executive Function System battery and the Dutch Rey Auditory Verbal Learning Test. We employed the Mann-Whitney U test to compare data between the CI and HA groups. We used Chi-square goodness of fit tests to contrast the CI and HA group distributions with the norm data of children who are typically developing (TD). We harnessed Kendall's Tau-b to investigate relationships between the study variables., Results: Both groups of children, with CIs and Has, obtained ceiling scores for perception of speech on a conversational level. However, the HA group exhibited significantly lower perception on a soft speech level scores (68 %) than the CI group (87%). No difference was present between the receptive vocabulary distributions of the CI and HA groups. The median receptive vocabulary standard scores for both groups were well within the normal range (CI group: 93; HA group: 96). In addition, we did not find any difference in EF between the CI and HA groups. For planning and verbal memory, the distributions of observed scores for children with CIs were different from the expected distributions of children who are TD. In both groups, a large proportion of children obtained below-average scores for planning (CI: 44%; HA: 33%) and for long-term verbal memory (CI: 44%; HA: 35%). In the HA group, perception at a soft speech level was associated with receptive vocabulary and planning. In the CI group, we did not find any associations., Conclusions: Both groups of children with severe and profound HL with HAs exhibit less favorable auditory perception on the soft speech level, but not at a conversational level, compared to children who are HH or deaf with CIs. Both groups, children with CIs and HAs, only exhibit more problems in planning and verbal memory than the norm groups of children who are TD. The results indicate that to obtain age-appropriate levels of receptive vocabulary and EF, the perception at the soft speech level is a necessary but not sufficient prerequisite., (Copyright © 2022 The Authors. Ear & Hearing is published on behalf of the American Auditory Society, by Wolters Kluwer Health, Inc.)

In the Western world, for deaf and hard-of-hearing children, hearing aids or cochlear implants are available to provide access to sound, with the overall goal of increasing their wellbeing. If and how this goal is achieved becomes increasingly multifarious when these children reach adolescence and young adulthood and start to participate in society in other ways. An approach to wellbeing that includes personal differences and the relative advantages and disadvantages that people have, is the capability approach, as developed by Nobel Prize laureate Amartya Sen. Capability is the set of real opportunities people have to do and be things they have reason to value. We interviewed 59 young people, aged 13 through 25, with cochlear implants (37) or hearing aids (22) to capture their capability. We found that their hearing devices enabled them to actively participate in a predominantly hearing society, with few differences between cochlear implant and hearing aid recipients. They did, however, report challenges associated with prejudices and expectations, and with feeling poorly understood, all of which appeared to impact their capability. Through the lens of capability, alleged differences between hearing aid and cochlear implant recipients began to fade. We discuss the implications for initiatives focused on the long-term support young recipients of hearing devices to meet their specific requirements over time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rijke, Vermeulen, Willeboer, Knoors, Langereis and van der Wilt.)

Introduction: The main idea underlying this paper is that impairments such as deafness are particularly relevant to the extent that they lead to deprivation of capability . Likewise, the impact of healthcare services such as cochlear implants and subsequent rehabilitation can best be inferred from the extent that they protect or restore capability of those affected., Methods: To explore children's post-implant capabilities, we tested two newly developed digital, adaptive child self-report and parent-report questionnaires in 19 deaf children (aged 8-12 years) and their parents during rehabilitation, as well as in 23 age peers with normal hearing., Results: Despite the impressive speech-language results that were recorded with cochlear implants, the post-implant capabilities of the deaf children we evaluated differed from those of their hearing peers, with the cochlear implant group appearing particularly disadvantaged in areas such as accessing information, communication, social participation, and participation in school., Conclusion: Deaf children with cochlear implants who are performing well on linguistic and auditory tests can still experience serious limitations in desired functioning. Our findings suggest that a capability approach may reveal aspects of what is being achieved through rehabilitation that might otherwise remain unnoticed, and that could help to further improve the well-being of our patients.IMPLICATIONS FOR REHABILITATIONOverall, children with cochlear implants appeared disadvantaged in certain capability areas, like accessing information, communication, social participation, and participation in school.It may be worthwhile to also ascertain capabilities in these children, representing a domain not covered by clinical measures, tapping directly into areas that are valuable to the patient.

An infant with congenital heart block and hemodynamically significant bradycardia underwent therapeutic temporary pacing wires placement. Post-operatively, frequent "asystole" alarms were observed on telemetry causing distress to both the family and the nursing staff. Investigation of these alarms showed that pacemaker malfunction led to monitor pseudo-malfunction. The alarms were alleviated with mindful setting of the pacemaker and telemetry monitor parameters. This case highlights the challenges of pacemaker placement and monitoring of very small infants in the intensive care setting. Awareness of these challenges would help in troubleshooting pacemaker and telemetry monitor issues.

Background: Impaired auditory speech perception abilities in deaf children with hearing aids compromised their verbal intelligence enormously. The availability of unilateral cochlear implantation (CI) auditory speech perception and spoken vocabulary enabled them to reach near ageappropriate levels. This holds especially for children in spoken language environments. However, speech perception in complex listening situations and the acquisition of complex verbal skills remains difficult. Bilateral CI was expected to enhance the acquisition of verbal intelligence by improved understanding of speech in noise., Methods: This study examined the effect of bilateral CI on verbal intelligence of 49 deaf children (3;5-8;0 years). Relations between speech perception in noise, auditory short-term memory and verbal intelligence were analysed with multiple linear regressions. In addition, the interaction of educational setting, mainstream or special, on these relations was analysed., Results: Children with bilateral CI obtained higher scores on verbal intelligence. Significant associations were present between speech perception in noise, auditory short-term memory and verbal intelligence., Conclusion: Children with simultaneous bilateral CIs showed better speech perception in noise than children with unilateral CIs, which mediated by the auditory short-term memory capacity, enhanced the ability to acquire more complex verbal skills for BICI children in mainstream education., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Prolactin elevation is a side effect of all currently available D(2) receptor antagonists used in the treatment of schizophrenia. Prolactin elevation is the result of a direct antagonistic D(2) effect blocking the tonic inhibition of prolactin release by dopamine. The aims of this work were to assess the correlation between in vitro estimates of D(2) receptor affinity and pharmacokinetic-pharmacodynamic model-based estimates obtained from analysis of clinical data using an agonist-antagonist interaction (AAI) model and to assess the value of such a correlation in early prediction of full prolactin time profiles. A population model describing longitudinal prolactin data was fitted to clinical data from 16 clinical phases 1 and 3 trials including five different compounds. Pharmacokinetic data were modeled for each compound and the prolactin model was both fitted in per-compound fits as well as simultaneously to all prolactin data. Estimates of prolactin elevating potency were compared to corresponding in vitro values and their predictability was evaluated through model-based simulations. The model successfully described the prolactin time course for all compounds. Estimates derived from experimental preclinical data and the model fit of the clinical data were strongly correlated (p<0.001), and simulations adequately predicted the prolactin elevation in five out of six compounds. The AAI model has the potential to be used in drug development to predict prolactin response for a given exposure of D(2) antagonists using routinely produced preclinical data.

A mechanistic pharmacokinetic/pharmacodynamic model is presented, characterizing the time course of prolactin in healthy as well as schizophrenic subjects following the administration of various doses and formulations of the antipsychotic drugs risperidone and paliperidone. Prolactin concentrations from nine studies (1,462 subjects) were analyzed in NONMEM. A competitive agonist-antagonist interaction model described the competition between these drugs and dopamine for the D(2) receptors that regulate prolactin release. Tolerance development was explained by a feedback loop with prolactin stimulating dopamine release, whereas models wherein tolerance is described in terms of depletion of a prolactin pool did not explain the data well. The diurnal prolactin rhythm was described by a two-period cosine function. Baseline prolactin was health-status dependent and higher in women than in men, although the drug-induced release was less than proportional to baseline. This quantitative mechanism-based model is the first to describe prolactin release in patients, and it confirms that paliperidone and risperidone have similar potencies for prolactin release.

Objectives: To investigate the speech perception performance of children with a cochlear implant (CI) after 3 and 4 years of follow-up and to study the influence of age at implantation, duration of deafness and communication mode on the variability in speech perception performance., Study Design: A broad battery of speech perception tests was administered to 67 children with a CI. The results were reduced into one measure: the 'equivalent hearing loss (EHL)'. This outcome measure refers to the performance of a reference group of severely and profoundly hearing impaired children with conventional hearing aids., Participants: The population comprised 35 congenitally, 17 pre-lingually and 15 post-lingually deaf children implanted between 1989 and 1999. The population was homogeneous with respect to cognition, residual hearing and support at home as a result of conservative inclusion criteria., Results: During the first 2 years after implantation, post-lingually deaf children showed the fastest rate of improvement in speech perception. After 3 years of implant use, the early implanted pre-lingually deaf children and congenitally deaf children implanted under the age of 6 years caught up with the post-lingually deaf children. Pre-lingually deaf children implanted after a relatively long-duration of deafness tended to show poorer performance than those with a shorter duration. Performance of congenitally deaf children implanted after the age of 6 years was poorer and progress was slower. In the congenitally deaf children, 36% of the variability in performance was explained by duration of deafness, whereas in the children with pre- and post-lingually acquired deafness, communication mode explained 69% of the variance., Conclusions: All children derived benefit from their CI for speech perception tasks, but performance varied greatly. Several children reached EHL levels around 70 dB; their speech perception was equal to that of a child with conventional hearing aids who has 70 dB HL. After early implantation, the levels of performance that were eventually achieved differed no more than 10 dB, irrespective of whether the onset of deafness was pre-lingual or postlingual. In congenitally deaf children, duration of deafness played a major role in speech perception performance, whereas in the children with pre-lingually and post-lingually acquired deafness together, mode of communication was a major factor.

The reading comprehension and visual word recognition in 50 deaf children and adolescents with at least 3 years of cochlear implant (CI) use were evaluated. Their skills were contrasted with reference data of 500 deaf children without CIs. The reading comprehension level in children with CIs was expected to surpass that in deaf children without implants, partly via improved visual word recognition. Reading comprehension scores of children with implants were significantly better than those of deaf children without implants, although the performance in implant users was substantially lagging behind that in hearing children. Visual word recognition was better in children with CIs than in children without implants, in secondary education only. No difference in visual word recognition was found between the children with CIs and the hearing children, whereas the deaf children without implants showed a slightly poorer performance. The difference in reading comprehension performance of the deaf children with and without CIs remained present when visual word recognition was controlled for. This indicates that other reading-related skills were also contributing to the improved reading comprehension skills of deaf children with CIs.

Objectives: To evaluate the long-term outcome of children with postmeningitic deafness and partial insertion of the Nucleus electrode array, and to compare their speech perception performance with that of children with full insertion of the electrode array., Design: A battery of seven speech perception tests was administered to 25 children with a cochlear implant (CI). Results were reduced into one score: equivalent hearing loss (EHL)., Setting: Tertiary referral centre., Participants: The partial insertion group comprised seven children, mean age at implantation 5.5 years, mean duration of deafness 3.6 years. The full-insertion control group comprised 18 children. Mean age at implantation: 4.4 years; mean duration of deafness: 2.9 years. All the children became deaf between 0 and 3 years of age., Main Outcome Measures: Over a 3-year follow-up period, the children with partial insertion showed continuing progress, although there was wide variation in performance and the rate of progression. Some open-set comprehension could even be achieved with the insertion of only eight electrodes of a nucleus device., Results: Three years after implantation, speech perception in the partial insertion children was poorer than that in the control groups with long (P < 0.01; 95% confidence interval 7-43 dB EHL) and short duration of deafness (P < 0.0001; 95% confidence interval 28-53 dB EHL). They showed slower progress and reached a poorer EHL plateau. Four of the seven children acquired open-set word recognition., Conclusions: Patients with partial insertion of the electrode array benefit from a CI, although less than patients with complete insertion.

Background: In 1999, an extensive study among bell pepper growers showed that a predatory mite, Amblyseius cucumeris, is a potentially relevant source of occupational allergens because 23% of the population had positive skin prick test reactions., Objective: To investigate whether cross-reactivity between A. cucumeris and Dermatophagoides pteronyssinus is responsible for the cosensitization to both mite species found in 58.7% of A. cucumeris-sensitized greenhouse workers., Methods: Fifteen serum samples from greenhouse workers with work-related inhalant allergy and a positive radioallergosorbent test (RAST) reaction to A. cucumeris or D. pteronyssinus were selected for immunoblot analysis using extracts of both mites. A subselection (n = 5) was used for RAST and immunoblot inhibition to investigate potential cross-reactivity., Results: On immunoblot, 2 distinct patterns were observed: one pattern showed common protein bands in A. cucumeris and D. pteronyssinus blots suggestive of cross-reactivity between A. cucumeris and D. pteronyssinus and the other pattern showed no shared protein bands. Dermatophagoides pteronyssinus RAST inhibition with A. cucumeris extract was low in 4 serum samples (<25% inhibition) and nearly absent in 1 serum sample; A. cucumeris RAST inhibition with D. pteronyssinus extract was high in 1 serum sample (75% inhibition), low in 2 serum samples (35% and <15% inhibition), and absent in 2 serum samples. These results were confirmed by immunoblot inhibition experiments., Conclusions: Amblyseius cucumeris, a new occupational allergen, has species-specific antigens and common antigens that are cross-reactive with the house dust mite D. pteronyssinus.

Background: In a previous investigation, a high prevalence of allergy to sweet bell pepper pollen was found among exposed horticulture workers. Allergy to plant-derived food is often the consequence of primary sensitization to common pollen allergens., Objective: We therefore investigated the cross-reactivity between sweet bell pepper pollen and pollen from grass, birch or mugwort., Method: We selected 10 sera from greenhouse workers who had, besides specific IgE against sweet bell pepper pollen, also IgE to grass, birch or mugwort pollen. Cross-reactivity was tested by the inhibition of IgE binding to solid-phase coupled sweet bell pepper pollen extract. The 10 sera were also analysed for IgE binding to sweet bell pepper pollen by immunoblotting., Results: With these sera, no or small inhibition of IgE binding to sweet bell pepper pollen extract was observed with grass, birch and mugwort pollen. With immunoblotting, major IgE-binding structures were seen at 14, 29 and 69 kDa in sweet bell pepper pollen extract., Conclusion: The results of our study demonstrate that sweet bell pepper pollen contains allergens that have no or limited cross-reactivity with common pollen allergens. With sera from the 10 patients tested, sensitization to sweet bell pepper pollen was not the consequence of primary sensitization to common pollen allergens.

Background: Protection against thrips, a common pest in bell pepper horticulture is effectively possible without pesticides by using the commercially available predatory mite Amblyzeius cucumeris (Ac). The prevalence of sensitization to Ac among exposed greenhouse employees and its clinical relevance was studied., Methods: Four hundred and seventytwo employees were asked to fill in a questionnaire and were tested on location. Next to RAST, skin prick tests (SPTs) were performed with common inhalant allergens, the storage mite Tyrophagus putrescentiae (Tp) which serves as a temporary food source during the cultivation process and Ac. Furthermore, nasal challenge tests with Ac were carried out in 23 sensitized employees., Results: SPTs positive to Ac were found in 109 employees (23%). Work-related symptoms were reported by 76.1%. Sensitization to Tp was found in 62 employees of whom 48 were also sensitized to Ac. Immunoglobulin (Ig)E-mediated allergy to inhalant allergens appeared to be an important risk factor for sensitization to Ac. Employees with rhinitis symptoms showed a significantly higher response to all Ac doses during the nasal challenge test compared with employees without rhinitis symptoms., Conclusions: The predatory mite Ac is a new occupational allergen in horticulture which can cause an IgE-mediated allergy in exposed employees. It is biologically active on the mucous membranes of the nose and therefore clinically relevant for the development of work-related symptoms.

Background: An increasing number of allergic complaints appear to have occurred among bell pepper greenhouse employees., Objective: The aim of this study was to estimate the prevalence of work-related allergic symptoms and the prevalence of sensitization to specific occupational allergens and its determinants., Methods: We studied 472 employees who were invited to answer an extensive questionnaire and to be tested on location with inhalant allergens and home-made extracts of the bell pepper plant. In addition, peak expiratory flow monitoring and RASTs were performed., Results: Work-related symptoms were reported in 53.8% of all cases. Sensitization to the bell pepper plant was found in 35.4%. Positive reactions to leaf, stem and/or juice, however, were associated in nearly 90% with sensitization to pollen, which appeared to be most important allergen of the plant. Sensitization to the bell pepper plant and inhalant atopy were considered the most important risk factors for the occurrence of work-related symptoms of the upper airways (PRR 2.63, CI 2.11-3.25 and PRR 2.25, CI 1.82-2.79) as well as of the lower airways (PRR 4.08, CI 2.38-7.00 and PRR 3.16, CI 1.87-5.33)., Conclusion: There is a surprisingly high prevalence of work-related respiratory symptoms (53.8%) in bell pepper horticulture. In two-thirds of the employees, symptoms at work were associated with an IgE-mediated allergy due to the high and chronic exposure to bell pepper pollen. Complaints at work without specific sensitization to bell pepper pollen can be caused by non-specific hyper-reactivity or atopy to other occupational allergens. The extent of this occupational allergy has important consequences for the health care of this large, still growing occupational group.

Background: The high incidence of occupational allergy in horticulture has only recently been recognized. We determined IgE against pollen and fruit from paprika and tomato plants in sera from 3 greenhouse workers and in 3 sera from food-allergic patients., Methods: Proteins in extracts of paprika and tomato pollen were incubated with patients' sera after covalent coupling of these proteins to agarose beads, or in immunoblots., Results: IgE against paprika pollen, but no IgE against tomato pollen, was found in serum from 2 greenhouse workers who worked with paprika plants only. IgE binding of these 2 sera to agarose-bound paprika pollen extract could be inhibited by paprika pollen but not by tomato pollen extract. A greenhouse worker, who cultivated tomato plants, had IgE against both tomato and paprika pollen. IgE binding of this serum to agarose-bound paprika pollen extract could be inhibited by both paprika pollen and tomato pollen extract. Three food-allergic patients also had IgE against tomato and paprika pollen. IgE from 2 food-allergic patients recognized IgE-binding structures in paprika or tomato pollen that were also present in fruit from the corresponding plant. In contrast, no substantial cross-reactivity was observed between paprika pollen and fruit towards IgE from 3 greenhouse workers. In 4 of 5 sera that were positive in the paprika pollen immunoblot major IgE binding to allergens of about 30 and 64 kD occurred., Conclusion: The presence of IgE against paprika or tomato pollen is not restricted to workers in horticulture; IgE against these pollen can also be present in food-allergic patients who have serum IgE against paprika and/or tomato fruit., (Copyright 2000 S. Karger AG, Basel.)

Background: The objective was to investigate whether venom immunotherapy with bumblebee venom (BBV) is safe and effective., Methods: Eleven patients with severe occupational anaphylaxis caused by stings of bumblebees were studied. Sensitization to bumblebee venom was confirmed by skin tests and RAST. Immunotherapy was started with bumblebee venom extract by the semirush procedure, because these patients showed a primary sensitization to Bombus venom, and a low or absent degree of cross-reactivity with honeybee venom. IgE titer and skin tests with bumblebee venom were performed yearly. Efficacy was evaluated by means of in-hospital sting challenge and/or occupational field stings from bumblebees., Results: All patients reached maintenance dose in 6 weeks without severe side-effects. During the follow-up period (1.5-5 years), three systemic reactions in two patients were seen in 20 bumblebee stings. However, these reactions were milder than the index sting., Conclusions: Immunotherapy with bumblebee venom is safe and effective, and is comparable with honeybee and yellow-jacket venom immunotherapy.

Basal auditory functions and early verbal communication skills were examined in young, profoundly deaf children with hearing aids or a cochlear implant. The hearing aid users (n = 23) were subdivided on the basis of their (unaided) hearing thresholds into: group A (pure tone average (PTA) at 0.5, 1 and 2 kHz: 90-100 dB HL); group B (PTA: 100-110 dB HL); and group C (PTA > 110 dB HL). All the children with a cochlear implant (n = 20) had a profound sensorineural hearing loss with a PTA that exceeded 120 dB HL. Functional hearing was evaluated by means of basal sound identification. The child's communication abilities with hearing aids or a cochlear implant were assessed using structured observations on the Scales of Early Communication Skills for Hearing Impaired Children. The basal auditory functions on a sound identification level improved over time in the cochlear implant users and groups A and B. Hardly any improvement was seen in group C. The performance of all the groups (either hearing aid or cochlear implant) on the Scales of Early Communication Skills for Hearing Impaired Children at 6 months after fitting the device and at later evaluations, was close to the average level for their age.

We describe 14 consecutive patients with complaints due to the handling of flowers. The symptoms varied from allergic rhinoconjunctivitis and asthma to urticaria. Most patients had professions in the flower industry. Skin prick tests (SPT) were performed with home-made pollen extracts from 17 different flowers known to be the most commonly grown and sold in The Netherlands RAST against mugwort, chrysanthemum, and solidago was performed. The diagnosis of atopy against flowers was based on work-related symptoms due to the handling of flowers, positive SPT with flower extracts, and positive RAST. The concordance between SPT and case history was 74%, and that between SPT and RAST was 77% Extensive cross-sensitization was seen to pollen of several members of the Compositae family (e.g., Matricaria, chrysanthemum, solidago) and to pollen of the Amaryllidaceae family (Alstroemeria and Narcissus). Homemade flower extracts can be used to confirm IgE-mediated flower allergy. Mugwort can be used as a screening test for possible flower allergy. For most patients, the allergy led to a change of profession.

Objective: To determine the speech perception of children with cochlear implants., Subjects and Methods: Speech perception results of seven children with cochlear implants (excellent performers), who showed stable speech recognition scores in the long term, were compared with those of severely hearing-impaired children with conventional hearing aids (reference group). The groups of children were matched according to their mean free-field aided thresholds., Results: The results of the open-set word recognition test were comparable in the two groups., Conclusion: If we consider the results of the hearing aid users as the gold standard, the results suggest that speech recognition in selected children with a cochlear implant is close to optimal.

The relation between age at cochlear implantation and long-term open-set speech recognition was studied in a group of nine congenitally deaf children. The age at cochlear implant surgery ranged from 4 to 13 years. The results showed that there was a tendency toward poorer results in the children implanted at a relatively older age. However, the results also indicated that an upper limit for age at implantation cannot yet be defined in these children.

In a previous paper, a method was introduced to transform the results obtained by children with a cochlear implant (CI) on a battery of speech perception tests into an overall value, the "equivalent hearing loss" value. This was achieved by matching the speech perception test scores with those of a reference group of children with conventional hearing aids and hearing loss ranging from 50 to 130 dB hearing level (HL). The equivalent hearing loss values of 16 prelingually deaf children with a CI were plotted as a function of time. There was considerable spread in the rate of progress made by the children in terms of the equivalent hearing loss values. The variables studied, age at onset of deafness/duration of deafness (in the present study, these two factors were indistinguishable) and the communication mode used at the children's school, accounted for 64% of the variance in speech perception performance. A plateau in the performance of the better performers was found which seemed to be caused by the level of hearing (the aided thresholds) with the CI.

The issue of whether an upper age limit should be set for cochlear implantation in congenitally deaf subjects has often been debated. To gain more insight, the speech perception abilities were analyzed of 12 congenitally deaf subjects whose age at the time of cochlear implantation ranged from 4 to 33 years. Subjects implanted during adulthood only showed progress during the first few months after the speech processor had been fitted and their long-term results were poor compared to those of children implanted early in life. This latter group showed steady improvement over the whole evaluation period. The present results support the notion that the earlier in life implantation is performed, the better the development of speech perception. Based on the progress-over-time profiles and data on actual daily use of the cochlear implant, it can be suggested that implantation of congenitally deaf subjects during or after puberty offers only limited benefit.

A steady decrease in serum IgE was noted in cardiac transplant recipients receiving a combination of cyclosporin A and prednisolone for immunosuppressive therapy. The average time period for the demonstration of a 50% decrease in serum IgE levels was calculated to be 40 +/- 16 days in 19 patients.

After i.v. administration of racemic metoprolol in the rat, the plasma concentrations of (R)- and (S)-metoprolol were comparable, and no differences in pharmacokinetic parameters between the two enantiomers were found. From the 3rd to the 12th month, comparable changes were seen for both enantiomers: there was an increase in the area under the plasma concentration-time curve (AUC) and a decrease in blood and plasma clearance. Half-life showed a significant prolongation, volume of distribution decreased between 3 and 12 months and increased between 12 and 24 months. After oral administration of the racemate, AUC and Cmax (maximum plasma concentration) were slightly higher, while oral clearance was slightly lower for (R)-metoprolol than for (S)-metoprolol. With aging, Cmax and AUC increased for both enantiomers, while oral clearance decreased. The change in oral clearance as a function of age is different between (S)- and (R)-metoprolol, and thus enantioselective. In vitro disappearance rate in 3-month-old rats was significantly higher for (S)-metoprolol than for (R)-metoprolol, although the difference was small. With aging, the disappearance rates of both enantiomers increased significantly, but not enantioselectively.

The pharmacokinetics of R- and S-atenolol after intravenous administration of racemic atenolol were studied in 3-, 12- and 24-month-old rats and in 3-month-old rats with renal failure induced by uranyl nitrate. In all age groups, the area under the plasma concentration-time curves is higher for R- than for S-atenolol; volume of distribution, total clearance and renal clearance are lower for R-atenolol than for S-atenolol, but the differences are small. In function of age there is for both enantiomers a significant increase in AUC, due, at least in part, to a decreased renal clearance; the effect of aging is not stereoselective. In rats with renal failure, the AUC of both enantiomers increases, due mainly to a decrease in renal clearance, but to a lesser degree also to a decrease in nonrenal clearance. For both enantiomers, the volume of distribution decreases and the half-life increases in the uraemic rats. The total amount of both enantiomers excreted in the urine is decreased in the rats with renal failure. There are no stereoselective effects of treatment of the rats with uranyl nitrate.

The influence of i.v. administration of 10 micrograms/kg recombinant human interleukin-1 beta (rhIL-1 beta), a putative mediator of inflammation, on the pharmacokinetics and metabolism of the propranolol enantiomers was studied in rats aged 3, 12 and 24 months. After oral administration of rac-propranolol to control rats of the three age groups, the plasma concentrations of (R)-propranolol were higher than those of (S)-propranolol. Administration of IL-1 beta increased the plasma concentrations of the (R)-enantiomer markedly and significantly, those of the (S)-enantiomer only to a lesser degree. For both enantiomers an important increase in plasma binding was found in the IL-1 beta-treated rats, which was linked to the increase in alpha 1-acid glycoprotein levels. The in vitro clearance, measured in 3-month-old rats using the 9000 g liver fraction, was for neither of the propranolol enantiomers influenced by IL-1 beta treatment, which is in keeping with the unchanged cytochrome P450 content. The enantioselective influence of IL-1 beta treatment on the pharmacokinetics of propranolol was also present in 12- and 24-month-old rats, although somewhat less pronounced in the latter group. Our results show an enantioselective influence of IL-1 beta treatment on the pharmacokinetics of propranolol in the rat, favouring the (R)-enantiomer.

The influence of age on stereoselective pharmacokinetics and in vitro metabolism of R- and S-hexobarbital was studied in the rat. After intravenous administration of the racemate, the plasma concentrations of S-hexobarbital are markedly lower than those of R-hexobarbital. For S-hexobarbital the half-life is somewhat shorter and the volume of distribution and plasma clearance is higher than for its antipode. For both enantiomers an increase in AUC and half-life, and a decrease in clearance are observed with aging. These changes occur mainly between the 3rd and the 12th month and are slightly more pronounced for R- than for S-hexobarbital, as appears from the S/R ratios. The volume of distribution shows no changes with aging. In vitro disappearance rate in 3-month-old rats is significantly higher for S- than for R-hexobarbital. There is for both enantiomers an increase in disappearance rate in 12-month-old rats as compared to younger or older rats, but this is significant only for the R-enantiomer. There are pronounced differences in the kinetics and metabolism of both hexobarbital enantiomers; changes with aging occur, but are only slightly and not always significantly more important for R- than for S-hexobarbital.

Fifty-two children with atopic dermatitis were investigated with the mixed-food radio-allergosorbent test (RAST) and the skin provocation test 'Skin Application Food Test' (SAFT). The mixed-food RAST is a commercially available test with multiple allergens on one disk. The disk contains 6 common food allergens: cow's milk, egg, peanut, soy, codfish and wheat. The SAFT is a system with which foods are applied to the skin in the state in which they are consumed. This test system is routinely used in our subdivision of Paediatric Dermatology in Sophia Children's Hospital. In some children, atopic dermatitis grew worse after a positive SAFT reaction. In 50% of the 38 children with food allergy a correlation was found between exacerbation/induction of atopic dermatitis and consumption or direct skin contact of foods to which the child was allergic. Due to direct skin contact of foods, atopic dermatitis can grow worse with sudden attacks of pruritus, especially on the hands and in the face. The SAFT imitates the naturally occurring symptoms, is child friendly and easy to perform. The mixed-food RAST can be used as a screening test to identify the children with atopic dermatitis and an atopic immune response to foods, so possibly food allergy. Further investigations of the sensitivity of the target organ (in atopic dermatitis: the skin) and the usefulness of the SAFT are then indicated.

The influence of aging on the pharmacokinetics and the tissue distribution of (R)- and of (S)-propranolol was studied in 3-, 12-, and 24-month-old rats. After both iv and oral administration of rac-propranolol, the plasma concentrations were higher for the (R)- than for the (S)-enantiomer. For the tissue concentrations, the reverse was true. The free fraction of (S)-propranolol in plasma was about 4 times larger than that of (R)-propranolol, and this is the main factor responsible for the differences in kinetics between the two enantiomers. There was a suggestion for a difference in tissue binding between the two enantiomers. With aging, the plasma and tissue concentrations of both enantiomers increase, probably due to a decrease in blood clearance. Tissue binding did not change much with aging. Notwithstanding the marked differences between the kinetics of the propranolol enantiomers, the changes which occur with aging affect both enantiomers to the same degree.

The aim of this study was to evaluate a new test for IgE antibody screening in children--the Phadiatop Paediatric. The mixture of allergens in this test contains the food and inhalant allergens for infants and children most relevant. 180 sera were selected from samples submitted for routine diagnostic IgE antibody assay. 91% of these sera were from children less than 5 year old. Half the sera were positive in RASTs that were initially requested by the physicians and the highest RAST scores for each serum were equally distributed over the range RAST class 1-4. 20 control sera were from children 1-4 years old. Results of the Phadiatop Paediatric were compared with results of the combination 'Phadiatop + mixed-food-RAST'. 22% of the sera that were negative in all RASTs that were initially requested by the physicians were positive in both tests. This suggests that an IgE antibody response to food components or inhalants was underdiagnosed in these cases. Whereas 135 sera were found positive in the Phadiatop Paediatric, only 116 sera had a positive Phadiatop result and/or a result of the mixed-food-RAST that was RAST class 1 (greater than or equal to 0.35 PRU/ml) or higher. In 11 of 16 sera with RAST class 0/1 (0.18-0.35 PRU/ml) in the mixed-food-RAST specific IgE against individual food allergens with RAST class 1 or higher could be demonstrated. Results of Phadiatop and Phadiatop Paediatric were not only expressed as 'positive' or 'negative', but also as a serum:reference ratio. Clinical documentation was collected retrospectively from the written case reports of 171 children.(ABSTRACT TRUNCATED AT 250 WORDS)

A sensitive high-performance liquid chromatographic method for the determination of the enantiomers of atenolol in rat plasma has been developed. Racemic atenolol and practolol (internal standard) were extracted from alkalinized plasma (pH 12) into dichloromethane containing 3% (v/v) heptafluoro-1-butanol, and the organic layer was evaporated. The samples were derivatized with (+)-1-(9-fluorenyl)ethyl chloroformate at pH 8.5 for 30 min. After removal of excess reagent, the diastereomers were extracted into dichloromethane. The diastereomers were separated on a Microspher C18 column (3 microns) with a mobile phase of acetonitrile-sodium acetate buffer (0.01 M, pH 7) (50:50, v/v) at a flow-rate of 0.8 ml/min. Fluorescence detection (lambda ex = 227 nm, lambda em = 310 nm) was used. When 100 microliters of plasma were used, the quantitation limit was 10 ng/ml for the atenolol enantiomers. The assay was applied to measure concentrations of atenolol enantiomers in plasma after intravenous administration of racemic atenolol to rats.

The enantiospecific determination of R- and S-hexobarbital in rat plasma is described. The method involves liquid-liquid extraction of racemic hexobarbital from plasma, separation of the underivatized enantiomers by high-performance liquid chromatography on an alpha 1-acid glycoprotein column and ultraviolet detection. The mobile phase consists of a phosphate buffer (pH 5.4) containing 0.4% 2-propanol as organic modifier. An alpha 1-acid glycoprotein guard column is used to increase the lifetime of the analytical column. Heptabarbital is the achiral internal standard. With detection limits of ca. 0.05 microgram/ml for both R- and S-hexobarbital, the assay is suitable for pharmacokinetic studies of the enantiomers in rats.