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1.
Eur Psychiatry ; 33: 18-36, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26854984

ABSTRACT

PURPOSE: Patients with chronic depression (CD) by definition respond less well to standard forms of psychotherapy and are more likely to be high utilizers of psychiatric resources. Therefore, the aim of this guidance paper is to provide a comprehensive overview of current psychotherapy for CD. The evidence of efficacy is critically reviewed and recommendations for clinical applications and research are given. METHODS: We performed a systematic literature search to identify studies on psychotherapy in CD, evaluated the retrieved documents and developed evidence tables and recommendations through a consensus process among experts and stakeholders. RESULTS: We developed 5 recommendations which may help providers to select psychotherapeutic treatment options for this patient group. The EPA considers both psychotherapy and pharmacotherapy to be effective in CD and recommends both approaches. The best effect is achieved by combined treatment with psychotherapy and pharmacotherapy, which should therefore be the treatment of choice. The EPA recommends psychotherapy with an interpersonal focus (e.g. the Cognitive Behavioural Analysis System of Psychotherapy [CBASP]) for the treatment of CD and a personalized approach based on the patient's preferences. DISCUSSION: The DSM-5 nomenclature of persistent depressive disorder (PDD), which includes CD subtypes, has been an important step towards a more differentiated treatment and understanding of these complex affective disorders. Apart from dysthymia, ICD-10 still does not provide a separate entity for a chronic course of depression. The differences between patients with acute episodic depression and those with CD need to be considered in the planning of treatment. Specific psychotherapeutic treatment options are recommended for patients with CD. CONCLUSION: Patients with chronic forms of depression should be offered tailored psychotherapeutic treatments that address their specific needs and deficits. Combination treatment with psychotherapy and pharmacotherapy is the first-line treatment recommended for CD. More research is needed to develop more effective treatments for CD, especially in the longer term, and to identify which patients benefit from which treatment algorithm.


Subject(s)
Antidepressive Agents/therapeutic use , Depressive Disorder , Psychotherapy/methods , Chronic Disease , Combined Modality Therapy/methods , Depression , Depressive Disorder/diagnosis , Depressive Disorder/psychology , Depressive Disorder/therapy , Diagnostic and Statistical Manual of Mental Disorders , Europe , Humans , Outcome and Process Assessment, Health Care , Psychiatric Status Rating Scales
2.
Tijdschr Psychiatr ; 57(10): 710-8, 2015.
Article in Dutch | MEDLINE | ID: mdl-26479250

ABSTRACT

BACKGROUND: Somatic disorders occur more often in psychiatric patients than in the general population. Somatic symptoms can cause or increase psychiatric symptoms. Psychiatric symptoms and their treatment can have an effect on the physical state of the patient. A pilot study involving an adult outpatient population has demonstrated that 62% of the patients studied had new clinically relevant symptoms. So far, no other data are available relating to somatic screening in child and adolescent psychiatry. AIM: To assess whether somatic screening of children and adolescents newly referred to a department of child and adolescent psychiatry in the Netherlands gives added value to the diagnosis and treatment policy. METHOD: In a pilot study 43 newly referred patients aged between 6 and 18 were screened by means of somatic history, a physical examination and blood parameters. On this basis we could calculate the percentage of somatic symptoms and , where necessary, follow-up treatment could be applied. RESULTS: One or more clinically relevant disorders were found in almost 56% of the children and adolescents investigated. The disorders included dysmorphic anomalies, weight and height deviations, raised thyroid hormone levels, dyslipidaemia, anaemia and vitamin D and B12 deficiency. Advice about a healthy lifestyle was given to 44% of the patients. An antipsychotic medication in 25% of the patients was changed, in the case of 16% of the patients a family doctor was contacted about subsequent treatment and 19% of the patients were referred to a medical specialist. CONCLUSION: Although the results of the pilot study indicate that somatic screening does provide added value, more research is needed in order to optimise the screening procedure.


Subject(s)
Chronic Disease/epidemiology , Health Status , Mental Disorders/epidemiology , Adolescent , Child , Comorbidity , Female , Humans , Male , Mental Disorders/diagnosis , Physical Examination , Pilot Projects
3.
Tijdschr Psychiatr ; 56(10): 670-9, 2014.
Article in Dutch | MEDLINE | ID: mdl-25327349

ABSTRACT

BACKGROUND: The a-theoretical approach to psychiatric disorders, introduced via dsm iii, has had a tremendous impact. It has stimulated a large body of research, facilitated by the concurrent development of new techniques in genetics, neuro-imaging and neuropsychology. However, the research results of the last twenty years or so have cast doubt on the validity of the clinical categories set out in dsm iii. AIM: To develop a new view on developmental pathways in psychopathology, clinical assessment and scientifically acceptable classification. METHOD: In this article we review the state of the art with regard to underlying endophenotypes at the level of brain and neurotransmitter functioning and neuropsychology and we consider the effect of social determinants on the developments of psychopathology. RESULTS: Our results show that neither genotypes and endophenotypes, nor brain mechanism, nor neuropsychological deviances have a one-to-one correlation with clinical categories as defined in even the dsm 5. CONCLUSION: dsm-5 provides a range of possibilities for classifying psychiatric disorders at symptom level. But these categories seem to be less distinct than was at first assumed. Recent research has shown that there is a great deal of overlap at the genetic, epigenetic and endophenotype level. This calls for more emphasis on individual assessment and diagnostics in both clinical practice and scientific research. More attention needs to be given to the dimensions of emotion and behavior, vulnerability and resilience. This type of approach, involving genotypes, endophenotypes, epigenetics and brain functioning, could help to elucidate the interaction between these various levels and/or explain the underlying mechanisms of psychiatric disorders.


Subject(s)
Mental Disorders/classification , Mental Disorders/diagnosis , Psychiatric Status Rating Scales , Epigenomics , Genotype , Humans , Personality Inventory , Phenotype , Psychometrics
4.
Eur Psychiatry ; 29(2): 83-100, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24506936

ABSTRACT

PURPOSE: To advance mental health care use by developing recommendations to increase trust from the general public and patients, those who have been in contact with services, those who have never been in contact and those who care for their families in the mental health care system. METHODS: We performed a systematic literature search and the retrieved documents were evaluated by two independent reviewers. Evidence tables were generated and recommendations were developed in an expert and stakeholder consensus process. RESULTS: We developed five recommendations which may increase trust in mental health care services and advance mental health care service utilization. DISCUSSION: Trust is a mutual, complex, multidimensional and dynamic interrelationship of a multitude of factors. Its components may vary between individuals and over time. They may include, among others, age, place of residence, ethnicity, culture, experiences as a service user, and type of disorder. For mental health care services, issues of knowledge about mental health services, confidentiality, continuity of treatment, dignity, safety and avoidance of stigma and coercion are central elements to increase trust. CONCLUSION: Evidence-based recommendations to increase mutual trust of service users and psychiatrists have been developed and may help to increase mental health care service utilization.


Subject(s)
Mental Disorders/psychology , Mental Disorders/therapy , Mental Health Services/standards , Professional-Patient Relations , Trust , Culture , Humans
5.
Eur Psychiatry ; 29(2): 101-6, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24503245

ABSTRACT

The European Union Free Movement Directive gives professionals the opportunity to work and live within the European Union, but does not give specific requirements regarding how the specialists in medicine have to be trained, with the exception of a required minimum of 4 years of education. Efforts have been undertaken to harmonize post-graduate training in psychiatry in Europe since the Treaty of Rome 1957, with the founding of the European Union of Medical Specialists (UEMS) and establishment of a charter outlining how psychiatrists should be trained. However, the different curricula for post-graduate training were only compared by surveys, never through a systematic review of the official national requirements. The published survey data still shows great differences between European countries and unlike other UEMS Boards, the Board of Psychiatry did not introduce a certification for specialists willing to practice in a foreign country within Europe. Such a European certification could help to keep a high qualification level for post-graduate training in psychiatry all over Europe. Moreover, it would make it easier for employers to assess the educational level of European psychiatrists applying for a job in their field.


Subject(s)
Curriculum , Education, Medical, Graduate , Psychiatry/education , Europe , Humans
6.
Tijdschr Psychiatr ; 55(1): 21-31, 2013.
Article in Dutch | MEDLINE | ID: mdl-23315693

ABSTRACT

BACKGROUND: Transparency by means of quality indicators is regarded as a method for monitoring and improving the quality of care. In the Dutch mental health service (GGZ) a generic basic set of indicators has been developed, but it is not clear whether the set is suitable for use in child and adolescent psychiatry. AIM: To assess whether the GGZ Basic Set of performance indicators for 2007-2008 was suitable for use in a child and adolescent psychiatric setting and to detect any omissions in that set. METHOD: A heterogeneous national group of eight health professionals and five 'stakeholders' in child and adolescent mental health judged the existing Basic Set by means of a Delphi procedure consisting of two written rounds and a panel discussion. The experts assessed potential indicators with regard to necessity, validity, clarity and applicability to child and adolescent psychiatry using a scale of 0 to 9. Indicators scoring more than 7 were considered to be appropriate. RESULTS: Only two of the 54 indicators were considered appropriate. A lower cut-off point would leave 16 indicators, of which 10 related to the outcome of treatment. One of the nine proposed innovative indicators was added. CONCLUSION: Very few of the indicators in the Basic Set were considered to be suitable for use in child and adolescent psychiatry. Respondents expressed a preference for a limited number of indicators that emphasised the opinion of the patient and of parents rather than the outcomes of treatment.


Subject(s)
Adolescent Psychiatry/standards , Child Psychiatry/standards , Practice Guidelines as Topic , Quality of Health Care , Adolescent , Benchmarking , Child , Delphi Technique , Female , Humans , Male , Netherlands
7.
Tijdschr Psychiatr ; 54(11): 965-72, 2012.
Article in Dutch | MEDLINE | ID: mdl-23138624

ABSTRACT

BACKGROUND: On the basis of our current knowledge, developmental disorders can be divided into the following stages: stage 0: normal variation, stage 1: simple disorder of moderate severity, stage 2: complicating co-morbidity and/or harmful background circumstances, and stage 3: serious disorder with harmful background circumstances. AIM: To describe the current views on prognostic aspects of staging from a developmental perspective. METHOD: The study is based on a critical review of the relevant literature. RESULTS: The current division into stages is still insufficiently predictive, partly because development is a flexible process with risks, chances and second chances. All psychiatric disorders are in essence developmental disorders that arise in the course of development as a result of the interaction between predisposition and background circumstances. As from the very first meiosis the hereditary predisposition is subject to influences in the womb environment. The forming of networks in the brain, the distribution of neurotransmitters and the neurological profile are influenced by the genetic potential for chances and risks and are all a result of interactions. This complicated developmental history raises questions about the specificity of current clinical syndromes. CONCLUSION: In time there is likely to be a much more accurate staging system. This will come about if, as a result of the analysis of large pooled databases, it becomes possible to make a better assessment of the relative risks of genetic configurations, brain connections, stress regulation in the brain, neuropsychological profiles and behavioural and emotional forms of expression in the light of the interactions that occur with the aforementioned background circumstances.


Subject(s)
Child Development Disorders, Pervasive/classification , Child Development Disorders, Pervasive/diagnosis , Developmental Disabilities/classification , Developmental Disabilities/diagnosis , Diagnostic and Statistical Manual of Mental Disorders , Adaptation, Psychological , Child , Diagnosis, Differential , Genetic Predisposition to Disease , Humans , Prognosis , Risk Factors , Social Environment , Treatment Outcome
8.
Cereb Cortex ; 20(8): 1937-45, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20016003

ABSTRACT

Language in high-functioning autism is characterized by pragmatic and semantic deficits, and people with autism have a reduced tendency to integrate information. Because the left and right inferior frontal (LIF and RIF) regions are implicated with integration of speaker information, world knowledge, and semantic knowledge, we hypothesized that abnormal functioning of the LIF and RIF regions might contribute to pragmatic and semantic language deficits in autism. Brain activation of sixteen 12- to 18-year-old, high-functioning autistic participants was measured with functional magnetic resonance imaging during sentence comprehension and compared with that of twenty-six matched controls. The content of the pragmatic sentence was congruent or incongruent with respect to the speaker characteristics (male/female, child/adult, and upper class/lower class). The semantic- and world-knowledge sentences were congruent or incongruent with respect to semantic expectancies and factual expectancies about the world, respectively. In the semantic-knowledge and world-knowledge condition, activation of the LIF region did not differ between groups. In sentences that required integration of speaker information, the autism group showed abnormally reduced activation of the LIF region. The results suggest that people with autism may recruit the LIF region in a different manner in tasks that demand integration of social information.


Subject(s)
Child Development Disorders, Pervasive/psychology , Language Development Disorders/psychology , Language Tests , Magnetic Resonance Imaging/psychology , Semantics , Social Behavior , Speech Perception/physiology , Adolescent , Brain Mapping , Child , Child Development Disorders, Pervasive/complications , Comprehension/physiology , Female , Frontal Lobe/anatomy & histology , Frontal Lobe/physiology , Frontal Lobe/physiopathology , Humans , Language Development Disorders/etiology , Magnetic Resonance Imaging/methods , Male , Neuropsychological Tests
9.
Brain ; 132(Pt 7): 1941-52, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19423680

ABSTRACT

Difficulties with pragmatic aspects of communication are universal across individuals with autism spectrum disorders (ASDs). Here we focused on an aspect of pragmatic language comprehension that is relevant to social interaction in daily life: the integration of speaker characteristics inferred from the voice with the content of a message. Using functional magnetic resonance imaging (fMRI), we examined the neural correlates of the integration of voice-based inferences about the speaker's age, gender or social background, and sentence content in adults with ASD and matched control participants. Relative to the control group, the ASD group showed increased activation in right inferior frontal gyrus (RIFG; Brodmann area 47) for speaker-incongruent sentences compared to speaker-congruent sentences. Given that both groups performed behaviourally at a similar level on a debriefing interview outside the scanner, the increased activation in RIFG for the ASD group was interpreted as being compensatory in nature. It presumably reflects spill-over processing from the language dominant left hemisphere due to higher task demands faced by the participants with ASD when integrating speaker characteristics and the content of a spoken sentence. Furthermore, only the control group showed decreased activation for speaker-incongruent relative to speaker-congruent sentences in right ventral medial prefrontal cortex (vMPFC; Brodmann area 10), including right anterior cingulate cortex (ACC; Brodmann area 24/32). Since vMPFC is involved in self-referential processing related to judgments and inferences about self and others, the absence of such a modulation in vMPFC activation in the ASD group possibly points to atypical default self-referential mental activity in ASD. Our results show that in ASD compensatory mechanisms are necessary in implicit, low-level inferential processes in spoken language understanding. This indicates that pragmatic language problems in ASD are not restricted to high-level inferential processes, but encompass the most basic aspects of pragmatic language processing.


Subject(s)
Autistic Disorder/psychology , Comprehension , Acoustic Stimulation/methods , Adolescent , Adult , Auditory Cortex/physiopathology , Auditory Perception , Autistic Disorder/physiopathology , Brain Mapping/methods , Communication , Female , Humans , Language Tests , Magnetic Resonance Imaging/methods , Male , Young Adult
10.
Ned Tijdschr Geneeskd ; 152(24): 1353-7, 2008 Jun 14.
Article in Dutch | MEDLINE | ID: mdl-18664210

ABSTRACT

Autism spectrum disorder was diagnosed in three adults. The first patient, a married man aged 41, was referred to a psychiatrist with 'impending burn-out'. The second was a 32-year-old male student with schizophrenia and a depressive disorder who was referred to a centre for autism because a friend of his mother's knew someone with Asperger's syndrome. The third patient was a 25-year-old woman with a 'fixation on food' who was referred by her general practitioner to a psychiatrist for evaluation of longstanding use of antidepressant medication. Autism used to be thought of as a condition of childhood. Only recently has the diagnosis and treatment of autism spectrum disorders become the focus of attention in adult psychiatry. It is made all the more difficult as during development into adulthood, the expression of disorders of reciprocal social interaction, communication, imagination and repetitive stereotypical thinking and actions, change.


Subject(s)
Asperger Syndrome/diagnosis , Autistic Disorder/diagnosis , Adult , Behavioral Symptoms , Communication Disorders/diagnosis , Communication Disorders/etiology , Diagnosis, Differential , Female , Humans , Interpersonal Relations , Male , Social Behavior Disorders/diagnosis , Social Behavior Disorders/etiology
11.
Ned Tijdschr Geneeskd ; 152(24): 1365-9, 2008 Jun 14.
Article in Dutch | MEDLINE | ID: mdl-18664213

ABSTRACT

Early infantile autism' as defined by Kanner has grown into a spectrum of autistic disorders. The recognition of Asperger's disorder and of pervasive developmental disorder not otherwise specified (PDD-NOS), has led to increased demand for appropriate diagnostic assessment of autism in adults. The expression ofimpairments in social interaction, communication, imagination and mental flexibility changes during development into adulthood. The diagnostic procedure in adult psychiatry should comprise a collateral developmental interview. Autism spectrum disorders in adults may mimic, or be overshadowed by, other psychiatric disorders. For effective diagnosis, the application of structured interviews, such as the 'Autism diagnostic observation schedule' (ADOS), 'Autism diagnostic interview-revised' (ADI-R) or 'Diagnostic interview for social and communication disorders' (DISCO) is recommended.


Subject(s)
Asperger Syndrome/diagnosis , Autistic Disorder/diagnosis , Child Development Disorders, Pervasive/diagnosis , Communication Disorders/diagnosis , Social Behavior Disorders/diagnosis , Adult , Asperger Syndrome/epidemiology , Autistic Disorder/epidemiology , Behavioral Symptoms , Child , Child Development Disorders, Pervasive/epidemiology , Communication Disorders/epidemiology , Diagnosis, Differential , Female , Humans , Male , Social Behavior Disorders/epidemiology
13.
J Clin Psychiatry ; 62(4): 239-48, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11379837

ABSTRACT

BACKGROUND: Risperidone is an atypical antipsychotic drug that blocks dopamine as well as serotonin receptor systems. The present study was designed to examine the efficacy and safety of risperidone in a 6-week double-blind, randomized, parallel-group design in the treatment of aggression in adolescents with a primary diagnosis of DSM-IV disruptive behavior disorders and with subaverage intelligence. METHOD: We randomly assigned 38 adolescents (33 boys; 10 subjects with slightly subaverage IQ, 14 with borderline IQ, and 14 with mild mental retardation), who were hospitalized for treatment of psychiatric disorders associated with severe aggression, to receive risperidone or placebo. The main efficacy measures were the Clinical Global Impressions-Severity of Illness scale (CGI-S), the modified Overt Aggression Scale (OAS-M), and the Aberrant Behavior Checklist (ABC). Side effects were measured using the Extrapyramidal Symptom Rating Scale (ESRS). RESULTS: The mean daily dose of risperidone at the end of treatment was 2.9 mg (range, 1.5-4 mg). Risperidone, compared with placebo, was associated with significant improvements on the CGI-S (p < .001) and the at-school ABC overall and hyperactivity scales (p < .05). During a 2-week washout following the 6-week trial, a statistically significant worsening was found in the risperidone group on the CGI-S scale, the OAS-M. and the ABC. Extrapyramidal symptoms were absent or very mild during risperidone treatment. Transient tiredness was present in 11 (58%) of 19 drug-treated subjects. Other untoward effects included sialorrhea, nausea, and slight weight gain (mean = 3.5% of body weight in the risperidone group). No clinically relevant changes were found in laboratory parameters, electrocardiogram, heart rate, or blood pressure. CONCLUSION: These results suggest that risperidone may be effective for severe aggression in adolescents with disruptive behavior disorders and subaverage intelligence, and these results are consistent with reports suggesting its effectiveness for treating severe aggression in adolescents in general.


Subject(s)
Aggression/drug effects , Antipsychotic Agents/therapeutic use , Attention Deficit and Disruptive Behavior Disorders/drug therapy , Hospitalization , Intellectual Disability/epidemiology , Risperidone/therapeutic use , Adolescent , Aggression/psychology , Antipsychotic Agents/adverse effects , Antipsychotic Agents/pharmacology , Attention Deficit and Disruptive Behavior Disorders/epidemiology , Attention Deficit and Disruptive Behavior Disorders/psychology , Basal Ganglia Diseases/chemically induced , Comorbidity , Double-Blind Method , Female , Humans , Male , Placebos , Psychiatric Status Rating Scales/statistics & numerical data , Risperidone/adverse effects , Risperidone/pharmacology , Severity of Illness Index , Treatment Outcome
14.
Br J Ophthalmol ; 84(11): 1238-43, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11049947

ABSTRACT

AIM: To study the value of polymerase chain reaction (PCR) analysis, to detect viral DNA in recipient corneal buttons taken at the time of penetrating keratoplasty (PKP) in patients with an initial diagnosis of herpetic stromal keratitis (HSK). Since HSK has a tendency to recur, an accurate diagnosis of previous HSK could be the reason to start antiviral treatment immediately, thereby possibly decreasing the number of graft failures due to recurrent herpetic keratitis. METHODS: Recipient corneal buttons and aqueous humour (AH) samples were obtained at the time of PKP from HSK patients (n=31) and from other patients (n=78). Eye bank corneas were also used (n=23). Herpes simplex virus type 1 (HSV-1), type 2 (HSV-2), and varicella zoster virus (VZV) infection were assessed by PCR and antibody detection. RESULTS: The clinical diagnosis HSK could be confirmed by PCR for HSV-1 in 10/31 (32%). In these corneal buttons HSV-2 DNA was detected in 1/31 (3%) and VZV DNA in 6/31 (19%). Intraocular anti-HSV antibody production was detected in 9/28 AH samples tested (32%). In the other patient derived corneas HSV-1 DNA was detected in 13/78 (17%), including eight failed corneal grafts without clinically obvious herpetic keratitis in the medical history. In clear eye bank corneas HSV-1 was detected in 1/23 (4%). CONCLUSIONS: PCR of HSV-1 on corneal buttons can be a useful diagnostic tool in addition to detection of intraocular anti-HSV antibody production. Furthermore, the results were suggestive for the involvement of corneal HSV infection during allograft failure of corneas without previous clinical characteristic signs of herpetic keratitis.


Subject(s)
Corneal Diseases/diagnosis , Corneal Transplantation , DNA, Viral/analysis , Eye Infections, Viral/virology , Herpes Simplex/diagnosis , Keratitis, Herpetic/diagnosis , Corneal Diseases/virology , Eye Infections, Viral/diagnosis , Herpesvirus 1, Human/isolation & purification , Herpesvirus 2, Human/isolation & purification , Herpesvirus 3, Human/isolation & purification , Humans , Keratitis, Herpetic/virology , Polymerase Chain Reaction
15.
Psychoneuroendocrinology ; 25(8): 753-64, 2000 Nov.
Article in English | MEDLINE | ID: mdl-10996471

ABSTRACT

In this study, we tried to replicate the finding of a diminished cortisol response to stress in autistic-like patients in a more homogenous Multiple Complex Developmental Disorder (MCDD) group. MCDD forms a distinct group within the autistic-like disorders, characterized by impaired regulation of anxiety and affective state, impaired social behavior/sensitivity, and thought disorder. A number of MCDD children develop schizophrenia in adult life. Responses to a psychosocial stressor, consisting of speaking in public while recorded on video, were measured in 10 MCDD children and 12 healthy control children. The public speaking test was imbedded in a two-hour test session, and compared to a control test session. Hypothalamic-pituitary-adrenal (HPA) responses were measured on salivary cortisol at about 20-minute intervals. Heart rate was measured continuously. Delta AUC's were computed for both heart rate (dAUCHR) and salivary cortisol (dAUCCORT), as a measure of response to the test.The public speaking task resulted in significant responses in heart rate and salivary cortisol in healthy control children, but not in MCDD children. dAUCHR was 3.28+/-2.37 in healthy control children, but -0.09+/-1.73 in MCDD children (t=3.31, P<0.01). dAUCCORT was 3.22+/-3.16 in healthy control children, but 0. 17+/-1.74 in MCDD children (t=2.72, P<0.05).The impaired responses to psychosocial stress found in MCDD children may be the result of their limited abilities to react adequately to their (social) environment. The same impairment in stress processing has been found in schizophrenia, and might be a factor in the vulnerability of these MCDD children to develop schizophrenia.


Subject(s)
Autistic Disorder/physiopathology , Stress, Psychological , Adrenal Glands/physiopathology , Autistic Disorder/psychology , Child , Female , Heart Rate , Humans , Hydrocortisone/analysis , Hypothalamus/physiopathology , Male , Pituitary Gland/physiopathology , Saliva/chemistry , Speech
16.
Invest Ophthalmol Vis Sci ; 41(8): 2239-47, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10892868

ABSTRACT

PURPOSE: In rats, corneal allograft rejection is delayed for at least 100 days by clodronate liposomes. These liposomes selectively deplete macrophages. To investigate the immunologic basis for absence of graft rejection in treated rats, the effect of these liposomes on the generation of cytotoxic T lymphocytes (CTLs) and antibody production after orthotopic corneal allotransplantation was determined. METHODS: Transplantations of corneal buttons from PVG rats were performed in AO rats. After surgery, one group received clodronate liposomes subconjunctivally at five time points, and the other group remained untreated. On postoperative day (POD) 3, 7, 12, or 17, rats were killed, the presence of CTLs was investigated at three different anatomic locations, and antibodies against donor antigens were tested. RESULTS: No significant differences were found between the groups tested 3 and 7 days after surgery. But on POD 12 (the time of onset of rejection in the untreated group) and on POD 17, the CTL activities detected in the submandibular lymph nodes (P < or = 0.008) and the spleen (P < or = 0.009) were significantly less in the treated groups compared with the untreated groups. In the untreated groups complement-independent antibodies were present only on POD 17, whereas no antibodies were found in the treated rats. CONCLUSIONS: Local treatment with clodronate liposomes was shown to downregulate local and systemic CTL responses and to prevent the generation of antibodies. Local depletion of macrophages in the initiation phase of the immune response appears to lead to a less vigorous attack on the grafted tissue and therefore to promote graft survival.


Subject(s)
Cornea/immunology , Corneal Transplantation/immunology , Graft Rejection/immunology , Macrophages/physiology , T-Lymphocytes, Cytotoxic/immunology , Animals , Clodronic Acid/administration & dosage , Cornea/drug effects , Cytotoxicity Tests, Immunologic , Cytotoxicity, Immunologic/immunology , Down-Regulation , Drug Carriers , Graft Rejection/prevention & control , Graft Survival/drug effects , Isoantibodies/analysis , Liposomes , Male , Rats , Rats, Inbred Strains , Transplantation, Homologous
17.
Ophthalmic Res ; 32(4): 157-64, 2000.
Article in English | MEDLINE | ID: mdl-10828736

ABSTRACT

Cytokine profiles in aqueous humour were studied in relation to corneal disease and subsequent corneal graft survival or rejection. Cytokine levels in samples obtained from eyes with clear grafts (n = 59) were all within the normal range. At the time of penetrating keratoplasty (n = 146), intraocular levels of IL-6 were increased in 38% (50/131), most markedly in eyes with previous allograft failure or herpetic stromal keratitis. The level of IL-10 was increased in 1 eye (n = 144) and of IL-4 and IFN-gamma in none. During rejection (n = 10), the levels of IL-6 in aqueous humour were increased in 75% (3/4), of IL-10 in 50% (3/6), of IL-4 in none (0/4) and of IFN-gamma in 40% (2/5). In conclusion, the levels of total protein and IL-6 were increased prior to penetrating keratoplasty in eyes with previous inflammation. These results could however not predict the final outcome of the graft. Increased intraocular levels of IL-6, IL-10 and IFN-gamma were observed during rejection.


Subject(s)
Aqueous Humor/metabolism , Cytokines/metabolism , Graft Rejection/metabolism , Keratoplasty, Penetrating , Adult , Aged , Aged, 80 and over , Biomarkers , Corneal Diseases/surgery , Enzyme-Linked Immunosorbent Assay , Female , Graft Rejection/immunology , Humans , Keratitis, Herpetic/metabolism , Male , Middle Aged , Prognosis , Retrospective Studies
18.
Curr Eye Res ; 20(4): 322-4, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10806446

ABSTRACT

PURPOSE: To test the effects of clodronate liposomes on graft survival and neovascularisation after transplantation in pre-vascularised recipient corneas. METHODS: Corneal neovascularisation was induced in F344 rats by injecting heat inactivated rabbit serum intrastromally. After 4 weeks F344 rats were orthotopically grafted with corneal buttons from DA rats. Directly after transplantation and on 2, 4, 6 and 8 days postoperatively clodronate liposomes were administrated subconjunctivally in one group, whereas the other group remained untreated. For 60 days grafts were observed for signs of graft rejection and neovascularisation. RESULTS: Graft survival was significantly prolonged, but not prevented in clodronate liposome treated rats compared to untreated rats ( p =.004). Also clodronate liposome administration delays growth of corneal neovascularisation after transplantation. CONCLUSIONS: Previous studies revealed that clodronate liposomes prevent corneal graft rejection and reduce neovascularisation in orthotopic corneal allotransplantation in rats. This study shows that also in pre-vascularised recipient corneas subconjunctival administration of clodronate liposomes seems to delay corneal graft rejection and reduces neovascularisation.


Subject(s)
Clodronic Acid/administration & dosage , Cornea/blood supply , Corneal Transplantation , Graft Rejection/prevention & control , Animals , Clodronic Acid/therapeutic use , Conjunctiva , Drug Carriers , Injections , Liposomes , Male , Neovascularization, Pathologic/etiology , Neovascularization, Pathologic/prevention & control , Rabbits/blood , Rats , Rats, Inbred F344 , Rats, Inbred Strains , Time Factors
19.
Invest Ophthalmol Vis Sci ; 40(13): 3194-201, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10586942

ABSTRACT

PURPOSE: Corneal allograft rejection in rats can be prevented by subconjunctival injections of liposomes containing dichloromethylene diphosphonate (clodronate-LIP), which selectively eliminate macrophages. In this study, the effect of clodronate-LIP treatment on cytokine mRNA levels in corneal allografts was examined. METHODS: AO rats received corneal grafts of PVG rats. Rats were either not treated or injected subconjunctivally with clodronate-LIP on the day of transplantation and on postoperative days (PODs) 2, 4, 6, and 8. RNA was isolated from the graft and rim of corneas at different times after transplantation and from normal controls. Interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1RA), IL-2, IL-4, IL-6, IL-10, IL-12p40, tumor necrosis factor (TNF)-alpha, TNF-beta/lymphotoxin (LT), interferon (IFN)-gamma, monocyte chemotactic protein 1 (MCP-1), and macrophage inflammatory protein 2 (MIP-2) mRNA levels were analyzed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Corneal rejection, observed in all untreated rats by POD 12, was associated with increased mRNA levels of all cytokines investigated in grafts and rims. Clodronate-LIP treatment prevented allograft rejection and strongly decreased the levels of IL-1beta, IL-1RA, IL-2, IL-4, IL-6, IL-10, IFN-gamma, TNF-beta/LT, MCP-1, and MIP-2 mRNA in grafts and IL-1 beta, IL-2, IL-4, IL-6, and IFN-gamma mRNA in rims. Interleukin-12p40 mRNA levels were unaltered in clodronate-treated rats, except for a transient increase in grafts at POD 3. TNF-alpha mRNA levels were increased by clodronate-LIP in grafts and rims early after transplantation (PODs 3 and 7). Despite a normal appearance, long-term accepted corneal grafts (POD 100) contained mRNA for IL-10, IL-12p40, TNF-alpha, MCP-1, and MIP-2. CONCLUSIONS: Clodronate-liposome treatment markedly altered the mRNA levels of all cytokines investigated in corneal allografts. These results may explain in part the mechanism by which clodronate-LIP treatment prevents corneal allograft rejection.


Subject(s)
Clodronic Acid/administration & dosage , Cornea/drug effects , Corneal Transplantation , Cytokines/genetics , Graft Rejection/prevention & control , RNA, Messenger/metabolism , Animals , Blotting, Southern , Chemokine CCL2/genetics , Chemokine CXCL2 , Cornea/metabolism , Cytokines/metabolism , Drug Carriers , Graft Rejection/metabolism , Graft Survival , Liposomes , Monokines/genetics , Rats , Rats, Inbred Strains , Reverse Transcriptase Polymerase Chain Reaction , Transplantation, Homologous
20.
J Child Psychol Psychiatry ; 40(6): 869-81, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10509882

ABSTRACT

This study was designed to examine the developmental and cognitive correlates of theory of mind (ToM) and emotion recognition ability in children with autism (N = 20), with pervasive developmental disorder-not otherwise specified (PDD-NOS) (N = 20), and in psychiatric control children (N = 20). The diagnostic groups were person-to-person matched on age and verbal IQ. The age of the children was between 8 and 18 years; their Full Scale IQ was at least 65. The test battery included tasks for the matching and the context recognition of emotional expressions, and a set of first- and second-order ToM tasks. The relationships between composite domain scores and the subjects' age, Verbal IQ, Performance IQ, verbal memory, visual memory, and gender were examined in bivariate and multivariate analyses. Further, the subjects who reliably and consistently passed the tasks of a domain and those who could not were compared on developmental and cognitive characteristics. Overall, the results of the various analyses converged and indicated that verbal memory, Performance IQ, age and gender were the best predictors of social cognitive ability.


Subject(s)
Autistic Disorder/psychology , Child Development Disorders, Pervasive/psychology , Cognition , Emotions , Memory , Social Behavior , Adolescent , Age Factors , Case-Control Studies , Child , Facial Expression , Female , Humans , Intelligence Tests , Male , Multivariate Analysis , Problem Solving , Psychiatric Status Rating Scales , Verbal Learning
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