RESUMEN

The British James Lind Alliance (JLA) has developed a method to allow practitioners, patients and family members together to develop a research agenda for a disease or a form of treatment. In a 'priority setting partnership', they gradually establish a top-10 list of the most important unanswered research questions. Input from patients and their relatives is given the same weight when determining priorities as that from practitioners. More than 50 of these top-10 lists have been created so far, one of which was created in the Netherlands. The JLA method combines elements of the two very different methods currently prevailing in the Netherlands: the dialog model, developed by the VU and the 'health care evaluation agenda', developed by the Dutch Association of Medical Specialists. The JLA method is quite practicable and leads to new research questions. The biggest advantage is that it leads to a dialogue between creators and users of knowledge about what the relevant research questions are.

Asunto(s)

RESUMEN

OBJECTIVE: To study the relationships of muscle strength and maximal oxygen consumption (VO(2peak)) with Childhood Health Assessment Questionnaire (CHAQ) score, Childhood Myositis Assessment Score (CMAS) and Child Health Questionnaire [physical summary (CHQ-PhS) and psychosocial summary (CHQ-PsS)] scores in juvenile dermatomyositis. METHOD: Fifteen patients (age 5-14 yr) participated. CMAS, CHAQ, CHQ, muscle strength and VO(2peak) were measured. RESULTS: Correlations revealed significant relationships between CHAQ and (i) muscle strength (r=-0.72) and (ii) absolute VO(2peak) (r=-0.68); between CMAS and relative VO(2peak) (r=0.73); and between CHQ-PhS and (i) muscle strength (r=0.57) and (ii) relative VO(2peak) (r=0.58). Backward regression analysis showed that muscle strength was the best indicator of variation in CHAQ. Age and relative VO(2peak) were the best indicators for CMAS. Body mass and age were the best indicators for CHQ-PsS. Body mass and muscle strength were the best indicators for CHQ-PhS. CONCLUSION: CMAS, CHAQ and CHQ correlate with muscle strength and VO(2peak). CMAS, CHAQ and CHQ depend on different physical and physiological variables.

Asunto(s)

RESUMEN

OBJECTIVE: To document the trend of the yearly number of newly diagnosed paediatric HIV-1 infections in the Netherlands. DESIGN: Retrospective registration regarding the period January 1st 1982-December 31st 1994 and prospective registration regarding January 1st 1995-December 31st 1997. METHOD: Based on reports to the Dutch Paediatric Surveillance Unit (Nederlands Signaleringscentrum Kindergeneeskunde) numbers of paediatric HIV-1 diagnoses (0-18 years) in the Netherlands were determined prospectively. Retrospective figures were determined by asking the paediatricians also to report the HIV-1 infected children diagnosed before the first of January 1995. A comparison was made with data from the Inspectorate for Health Care (Inspectie voor de Gezondheidszorg). All reports were followed up with standard questionnaires. RESULTS: In both periods an increase in the number of newly diagnosed paediatric HIV-1 infections per year in the Netherlands was seen (1982-1994: 74 children; 1995-1997: 43 children). The majority of the parents of the HIV-1 infected children originated from outside the Netherlands (1982-1994: 57%; 1995-1997: 91%), often from HIV-endemic countries (1982-1994: 41%; 1995-1997: 77%). The main mode of infection was vertical transmission (1982-1994: 62%; 1995-1997: 84%); diagnosis in allochtonous children was made relatively late. CONCLUSION: The current rise in the absolute number of newly detected paediatric HIV-1 infections in the Netherlands is predominantly due to the growing group of children born to parents who originate from HIV-endemic countries.

Asunto(s)

Asunto(s)

RESUMEN

Adjuvant arthritis (AA) in Lewis rats is T-cell mediated and seems to depend on T cells recognising the 180-188 epitope of mycobacterial heat-shock protein (hsp) 60. Analysis of arthritogenic T-cell clone A2b has revealed a mimicry of this particular epitope with an articular cartilage-associated target T-cell epitope. Nasal administration of synthetic peptides covering this 180-188 sequence led to epitope-specific tolerance and resistance to AA. Since this tolerisation protocol also inhibited avridine arthritis, one may conclude that this form of epitope-specific tolerance had effectuated a spreading tolerisation at the level of target antigens that included a diverse set of possible arthritis-associated antigens. In vitro anergised T cells exhibited suppressive activity in a co-culture system. As in this case--depending on the presence of the antigen of the anergic T cell--such T cells suppressed responder T cells of a different antigenic specificity, we postulated that anergic T cells may be responsible for a spreading of tolerance. It seemed that such spreading of tolerance was channelled through the antigen-presenting cells (APC) and was dependent on direct cell-cell contact. This and additional forms of spreading of tolerance could be responsible for specific nasal tolerance, causing inhibition of the development of an arthritogenic inflammatory response. This can be similarly the case for the arthritis protection that resulted from immunisation with hsps. Analysis of T-cell responses following hsp immunisations revealed that the arthritis inhibitory activity resided in T cells with specificity for a conserved part of microbial hsp 60. The same T cells cross-responded to rat self-hsp60. Low level expression of the latter molecule on non-professional APC could possibly have induced a suppressive anergic state in these autoreactive cells. Thus, immunisation with microbial hsp would have led to an expansion of such T cells, leading to raised disease-suppressive potential when selectively trapped and activated in the inflamed self-hsp-overexpressing joint. Alternatively, the cross-recognised self-hsp epitope could have the regulatory qualities of an altered peptide ligand or a partial agonist for T cells that see the microbial homologue as the full agonist.

Asunto(s)

RESUMEN

The relationships between bacterial heat shock proteins (HSPs) and autoimmunity were first disclosed in the mycobacteria-induced model of adjuvant arthritis: passive transfer of a T cell clone responding to mycobacterial HSP60 evoked disease in naive recipient animals. However, the disease could not be induced by immunization with HSP60, but instead protection was established. Subsequently, similar protection was found in experimental models of arthritis that do not involve challenge with bacterial antigens for the induction of disease. This rather general protective potency of bacterial HSPs against arthritis seems to result from the capacity of strongly conserved sequences in the protein to activate T cells that cross-recognize the mammalian homologous HSP-sequences presented on cells at the site of inflammation. It is possible that immunological recognition of bacterial HSPs is part of a general strategy used by the immune system for the regulatory control of the potentially harmful recognition of autoantigens as a hedge against the development of autoimmune disease.

Asunto(s)

Asunto(s)

RESUMEN

The impact of systemic onset JCA on functional outcome was studied in a multidimensional construct. Twenty-one patients were subjected to auxologic evaluation, a laboratory check, pulmonary and cardiac function tests, radiographic evaluation, joint count on tenderness, swelling and function, ADL, health assessment (CHAQ), and psychosocial evaluation. Six of 21 patients had active systemic disease. Restrictive pulmonary function was found in 8/17 patients, 1/21 had pericarditis. Joint impairment was moderate. Functional limitations were mild. Self-esteem was positive. Parental report on functional limitation correlated significantly with joint impairment. Performance of daily activities correlated strongly with perceived competence. Active inflammatory disease did not correlate with joint impairment and functional limitation. Patients with systemic onset JCA develop mild functional limitations, which partially correlate with the more serious impairments. Pulmonary function disorders are a common impairment. Active inflammatory disease might influence functional outcome, but there is no evidence that it influences joint impairment outcome.

Asunto(s)

RESUMEN

UNLABELLED: We describe the case history of a 13-year-old girl with chronic fatigue and prolonged microcytic anaemia. She received oral iron since the age of 11 but failed to respond to it. Laboratory studies revealed elevated C-reactive protein and hypergammaglobulinaemia. A large solitary mesenterial lymph node could be demonstrated by ultrasonography and CT. A diagnosis of Castleman disease was suspected and confirmed histologically. After surgical removal of the lymphoma the patient recovered completely. CONCLUSION: Castleman disease should be considered in cases of chronic fatigue, unexplained fever, microcytic anaemia and hypergammaglobulinaemia.

Asunto(s)

RESUMEN

OBJECTIVE: To determine whether T lymphocyte reactivity to endogenous human hsp60 plays a regulatory role in the course of oligoarticular juvenile rheumatoid arthritis (JRA). METHODS: A prospective, longitudinal study of T cell reactivity to HSP in 15 patients with newly diagnosed HLA-B27 negative oligoarticular JRA was performed. Results were compared with those in a group of 20 patients with newly diagnosed polyarticular or systemic JRA or with acute arthritis caused by other systemic diseases or viral infections, as well as with those in a group of 9 healthy control subjects. RESULTS: In 86% of the patients with oligoarticular JRA (13 of 15), significant T lymphocyte proliferative responses to hsp60 were found in peripheral blood mononuclear cells and/or synovial fluid mononuclear cells within 3 months after the onset of arthritis. Only 5% of the patients in the rheumatologic disease control group (1 of 20) showed such positivity. All patients with oligoarticular JRA and positive responses to human hsp60 developed a remission of their disease within 12 weeks. During this period of remission, blood samples were taken from 8 patients and showed significantly lower and even negative responses to hsp60, compared with active disease, when all 8 patients had good responses. CONCLUSION: The results show that significant proliferative responses to human hsp60 can be found early in the course of oligoarticular JRA. Furthermore, these responses correlate with disease activity in such a manner that T cell reactivity to human hsp60 seems to be associated with disease remission.

Asunto(s)

RESUMEN

To assess the impact of disease on the functional outcome of patients with polyarticular juvenile chronic arthritis (JCA), the relationship between impairments and functional limitations was studied. Therefore, variables from the impairment domain were correlated with variables of the functional limitation domain and outcome variables were analysed for differences as a result of inflammatory disease, rheumatoid factor (RF), disease duration and age at onset. Twenty-three patients with polyarticular JCA were subjected to auxologic evaluation, a laboratory check, radiographic evaluation, joint count on tenderness and swelling, joint mobility/deformity examination, functional assessment of skills, health assessment and psychosocial evaluation. Inflammatory disease parameters, like CRP, ESR, thrombocytosis and leucocytosis, were increased in 6/23 patients. The parameters of the impairment domain, like joint tenderness and swelling, showed mild outcome, while parameters of the functional limitation domain showed more severe outcome. Generally, perceived competence was found to be normal. A clinically relevant number of patients (10/13) showed low scores on the activity factor of the Child Behaviour Check List (CBCL). A significant relationship was found between inflammatory disease variables and functional limitation outcome. RF seropositivity was not a good outcome predictor. Disease duration and age of onset showed no significant difference in the outcome of the domains. Significant correlation was found between the parental report of the Childhood Health Assessment Questionnaire (CHAQ) and all impairment parameters. Joint swelling showed a significant relationship with CHAQ and Juvenile Arthritis Functional Assessment Report (JAFAR). Disability outcome did not correlate with functional limitation. In general, children with polyarticular JCA function rather well when using a multidomain evaluation approach. Compensatory and adaptational mechanisms might contribute to the poor correlation between impairment and functional limitation parameters. Laboratory evaluation of inflammatory disease, a joint count of swollen joints and parent's report of the child's health status related best in our study.

Asunto(s)

Asunto(s)

RESUMEN

Vitamin B12 deficiency is an uncommon disorder in a prosperous western country. In two children a nutritional vitamin B12 deficiency was observed. The first was a 2-year-old girl with neurodevelopmental regression and macrocytic anaemia, a result of a combination of a maternal vitamin B12 deficiency and inadequate feeding after birth. The second patient was a 14-year-old adipose girl with severe polyneuropathy and mild macrocytic anaemia as a result of a nutritional vitamin B12 deficiency. In her case the deficiency resulted from a bizarre feeding pattern. She turned out to be the victim of child abuse. It is concluded that even in a prosperous western country like the Netherlands vitamin B12 deficiency in children can develop as a result of an inadequate feeding pattern. It can lead not only to macrocytic anaemia but also to severe neurological abnormalities.

Asunto(s)

RESUMEN

12 HIV-infected children were treated with a high dose of zidovudine (800/mg/m2/day) during a mean follow up period of 18 months. After starting treatment with zidovudine there was a subjective improvement and an increase in body weight, and a significant decline in serum HIV-antigenemia (p < 0.01) and serum IgG levels (p < 0.05). Zidovudine was generally well tolerated but there was serious hematological toxicity. In 9 patients (75%) dose reduction was necessary because of severe anemia (3 patients) or leucopenia (6 patients). Because of the high incidence of these side effects the starting dose of zidovudine was reduced to 600 mg/m2/day. These results confirm that zidovudine can safely be used to treat HIV-infected children. The main limitation is serious hematological toxicity which appears to be dose-related.

Asunto(s)

RESUMEN

The case is described of an eleven-year-old boy with abdominal pain and hematuria. The hematuria appears to be fabricated by the father of the boy by adding cooked meat to the urine samples. The medical history of the father is very suspect for the Münchhausen syndrome. The case of the son differs in some respects from the normal pattern of the Münchhausen by proxy syndrome: the age of the son, the role of the father as active inducer and the low social class of the family.

Asunto(s)