RESUMO
As biomarkers are lacking, multi-item questionnaire-based tools like the Positive and Negative Syndrome Scale (PANSS) are used to quantify disease severity in schizophrenia. Analyzing composite PANSS scores as continuous data discards information and violates the numerical nature of the scale. Here a longitudinal analysis based on Item Response Theory is presented using PANSS data from phase III clinical trials. Latent disease severity variables were derived from item-level data on the positive, negative, and general PANSS subscales each. On all subscales, the time course of placebo responses were best described with Weibull models, and dose-independent functions with exponential models to describe the onset of the full effect were used to describe paliperidone's effect. Placebo and drug effect were most pronounced on the positive subscale. The final model successfully describes the time course of treatment effects on the individual PANSS item-levels, on all PANSS subscale levels, and on the total score level.
Assuntos
Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adulto , Idoso , Ensaios Clínicos Fase III como Assunto , Método Duplo-Cego , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Palmitato de Paliperidona , Efeito Placebo , Escalas de Graduação Psiquiátrica , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto JovemRESUMO
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.
Assuntos
Isoxazóis/sangue , Modelos Biológicos , Prolactina/sangue , Prolactina/metabolismo , Pirimidinas/sangue , Risperidona/sangue , Interações Medicamentosas/fisiologia , Feminino , Humanos , Isoxazóis/farmacologia , Masculino , Palmitato de Paliperidona , Prolactina/agonistas , Prolactina/antagonistas & inibidores , Pirimidinas/farmacologia , Risperidona/farmacologiaRESUMO
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.
Assuntos
Implante Coclear , Surdez/diagnóstico , Percepção da Fala , Adolescente , Fatores Etários , Criança , Pré-Escolar , Comunicação , Surdez/congênito , Surdez/etiologia , Seguimentos , Humanos , Lactente , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Fala , Fatores de Tempo , Resultado do TratamentoRESUMO
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.
Assuntos
Implante Coclear/métodos , Surdez/fisiopatologia , Surdez/terapia , Meningite/complicações , Percepção da Fala/fisiologia , Limiar Auditivo/fisiologia , Criança , Pré-Escolar , Surdez/etiologia , Seguimentos , Humanos , Valor Preditivo dos Testes , Fatores de Tempo , Resultado do TratamentoRESUMO
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.
Assuntos
Doenças dos Trabalhadores Agrícolas/imunologia , Capsicum/imunologia , Pólen/imunologia , Rinite Alérgica Sazonal/imunologia , Alérgenos/imunologia , Especificidade de Anticorpos , Artemisia/imunologia , Betula/imunologia , Reações Cruzadas , Ambiente Controlado , Humanos , Imunoglobulina E/sangue , Poaceae/imunologia , Testes Cutâneos/métodosRESUMO
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.
Assuntos
Doenças dos Trabalhadores Agrícolas/epidemiologia , Alérgenos/imunologia , Hipersensibilidade Imediata/epidemiologia , Ácaros/imunologia , Rinite/epidemiologia , Doenças dos Trabalhadores Agrícolas/diagnóstico , Doenças dos Trabalhadores Agrícolas/etiologia , Animais , Capsicum , Estudos Transversais , Humanos , Hipersensibilidade Imediata/diagnóstico , Hipersensibilidade Imediata/etiologia , Ácaros/classificação , Testes de Provocação Nasal , Exposição Ocupacional , Prevalência , Teste de Radioalergoadsorção , Rinite/diagnóstico , Rinite/etiologia , Inquéritos e QuestionáriosRESUMO
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.
Assuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Poluentes Ocupacionais do Ar/imunologia , Alérgenos/imunologia , Capsicum/química , Ambiente Controlado , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Adulto , Fatores Etários , Especificidade de Anticorpos/imunologia , Estudos Transversais , Feminino , Humanos , Imunização , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Pico do Fluxo Expiratório/fisiologia , Pólen/efeitos adversos , Pólen/imunologia , Prevalência , Teste de Radioalergoadsorção , Fatores de Risco , Índice de Gravidade de Doença , Testes CutâneosRESUMO
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.
Assuntos
Capsicum/imunologia , Immunoblotting , Imunoglobulina E/imunologia , Plantas Medicinais , Pólen/imunologia , Solanum lycopersicum/imunologia , Adulto , Alérgenos/imunologia , Antígenos/imunologia , Criança , Feminino , Hipersensibilidade Alimentar/etiologia , Humanos , Imunoglobulina E/sangue , Masculino , Doenças Profissionais/etiologiaRESUMO
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.
Assuntos
Anafilaxia/terapia , Venenos de Abelha/imunologia , Hipersensibilidade/complicações , Hipersensibilidade/terapia , Imunoterapia , Doenças Profissionais/terapia , Adulto , Anafilaxia/etiologia , Feminino , Seguimentos , Humanos , Imunoterapia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/etiologia , Testes Cutâneos , Resultado do TratamentoAssuntos
Alérgenos/imunologia , Colagenases/metabolismo , Líquido da Lavagem Nasal/química , Rinite Alérgica Perene/imunologia , Ribonucleases , Animais , Proteínas Sanguíneas/metabolismo , Poeira/efeitos adversos , Proteínas Granulares de Eosinófilos , Habitação , Humanos , Mediadores da Inflamação/metabolismo , Metaloproteinase 9 da Matriz , Ácaros/imunologia , Testes de Provocação Nasal , Poaceae/imunologia , Pólen/imunologiaRESUMO
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.
Assuntos
Implante Coclear , Auxiliares de Audição , Perda Auditiva Neurossensorial/terapia , Testes de Discriminação da Fala/métodos , Percepção da Fala/fisiologia , Fala/fisiologia , Audiometria de Tons Puros/métodos , Criança , Pré-Escolar , Feminino , Perda Auditiva Neurossensorial/diagnóstico , Humanos , Masculino , Resultado do TratamentoRESUMO
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.
Assuntos
Hipersensibilidade/imunologia , Exposição Ocupacional , Plantas/imunologia , Adulto , Feminino , Humanos , Hipersensibilidade/diagnóstico , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Teste de Radioalergoadsorção , Testes CutâneosRESUMO
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.
Assuntos
Implante Coclear , Surdez/cirurgia , Auxiliares de Audição , Percepção da Fala , Audiometria de Tons Puros , Limiar Auditivo , Criança , Pré-Escolar , Surdez/diagnóstico , Humanos , Estudos Longitudinais , Índice de Gravidade de Doença , Fatores de TempoRESUMO
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.
Assuntos
Implante Coclear , Surdez/congênito , Surdez/cirurgia , Percepção da Fala , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Humanos , Teste do Limiar de Recepção da FalaRESUMO
A new measure has been developed to quantify the speech perception performance of children with a cochlear implant (CI). The method summarizes the speech perception scores obtained on a battery of tests that ranges from very basal tasks up to open speech recognition. The overall performance of a child with a CI on the test battery at a certain time during follow-up is matched to that of a reference group of severely and profoundly hearing-impaired children with conventional hearing aids. This matching procedure results in the expression of the speech perception scores of a child with a CI as an "equivalent hearing loss" value. The equivalent hearing loss concept deals adequately with floor and ceiling effects which inevitably occur when a battery with such a large range of tests is used. To illustrate this, application of the procedure to three children with a CI showed that before implantation, while they were using conventional hearing aids, the equivalent hearing loss was above 120 dB hearing level (HL). At 3 years' follow-up the equivalent hearing loss improved to 70 dB HL in the two children with an aetiology of meningitis. This means that these children were performing as well as children in the reference group with a hearing loss of 70 dB HL. The child with congenital deafness showed minor improvements over time.
Assuntos
Implantes Cocleares , Surdez/reabilitação , Auxiliares de Audição , Perda Auditiva/reabilitação , Percepção da Fala , Criança , Testes Auditivos , Humanos , Testes de Discriminação da FalaRESUMO
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.
Assuntos
Implantes Cocleares , Surdez/reabilitação , Auxiliares de Audição , Idade de Início , Criança , Pré-Escolar , Surdez/congênito , Surdez/etiologia , Testes Auditivos , Humanos , Meningite/complicações , Testes de Discriminação da FalaRESUMO
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.
Assuntos
Implantes Cocleares , Surdez/reabilitação , Adolescente , Adulto , Fatores Etários , Estudos de Casos e Controles , Criança , Pré-Escolar , Surdez/congênito , Surdez/fisiopatologia , Seguimentos , Humanos , Testes de Discriminação da Fala , Percepção da Fala , Fatores de TempoAssuntos
Surdez , Inteligibilidade da Fala , Medida da Produção da Fala , Adolescente , Adulto , Audiometria de Tons Puros , Criança , Pré-Escolar , Surdez/diagnóstico , HumanosRESUMO
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.