Overview of diagnosis and management of paediatric headache. Part I: diagnosis

Headache is the most common somatic complaint in children and adolescents. The evaluation should include detailed history of children and adolescents completed by detailed general and neurological examinations. Moreover, the possible role of psychological factors, life events and excessively stressful lifestyle in influencing recurrent headache need to be checked. The choice of laboratory tests rests on the differential diagnosis suggested by the history, the character and temporal pattern of the headache, and the physical and neurological examinations. Subjects who have any signs or symptoms of focal/progressive neurological disturbances should be investigated by neuroimaging techniques. The electroencephalogram and other neurophysiological examinations are of limited value in the routine evaluation of headaches. In a primary headache disorder, headache itself is the illness and headache is not attributed to any other disorder (e.g. migraine, tension-type headache, cluster headache and other trigeminal autonomic cephalgias). In secondary headache disorders, headache is the symptom of identifiable structural, metabolic or other abnormality. Red flags include the first or worst headache ever in the life, recent headache onset, increasing severity or frequency, occipital location, awakening from sleep because of headache, headache occurring exclusively in the morning associated with severe vomiting and headache associated with straining. Thus, the differential diagnosis between primary and secondary headaches rests mainly on clinical criteria. A thorough evaluation of headache in children and adolescents is necessary to make the correct diagnosis and initiate treatment, bearing in mind that children with headache are more likely to experience psychosocial adversity and to grow up with an excess of both headache and other physical and psychiatric symptoms and this creates an important healthcare problem for their future life

Genetics of human T cell-monocyte interaction in helper cell induction.

The generation of human antigen-specific helper cells from unprimed peripheral blood lymphoid cells in tissue culture requires the presence of the appropriate number of blood monocytes. The role of the HLA complex in this cell interaction was investigated, by using HLA-type donors, and it was found that the monocytes had to share at least one HLA-DR specificity with the T cell donor. These experiments suggested that the genes controlling the macrophage-T cell interaction are closely associated or in linkage disequilibrium with the HLA-DR region

Genetics of human T cell-monocyte interaction in helper cell induction.

The generation of human antigen-specific helper cells from unprimed peripheral blood lymphoid cells in tissue culture requires the presence of the appropriate number of blood monocytes. The role of the HLA complex in this cell interaction was investigated, by using HLA-type donors, and it was found that the monocytes had to share at least one HLA-DR specificity with the T cell donor. These experiments suggested that the genes controlling the macrophage-T cell interaction are closely associated or in linkage disequilibrium with the HLA-DR region

Expression of alloantigens LY-5 and LY-6 on cytotoxic effector cells.

With anti-Ly antisera and complement it has been possible to demonstrate that cytotoxic effector cells generated in vitro against allogeneic cells carry the alloantigen Ly-5 and Ly-6. The studies show that antisera directed against the Ly-6 antigens, together with complement, eliminate essentially all of the killer cells, of the appropriate strain, while killing only 50 to 60% of Thy-1+ cells. Anti-Ly-5 antsera and complement lysed 55 to 65% of Thy-1+ cells and killed a significant portion, but not all, of the cytotoxic cells. The later finding was investigated in more detail since it suggested a degree of heterogeneity within the killer cell subpopulation. However, the data did not support that conclusion, at least for allogeneic killer cells

The transfer of a laboratory based hypothesis to a clinically useful therapy: the development of anti-TNF therapy of rheumatoid arthritis.

The development of anti-TNF therapy is a key step forward in rheumatology as it is the first new therapy for based on investigating the molecular mechanisms of this disease. This chapter reviews how this discovery was made

Comparison of antigen-specific I-region-associated cell interaction factors.

Two basic types of factors reacting with anti-I region (anti-Ia) antisera are compared, those derived from macrophage-like antigen presenting cells and others derived from T-lymphocytes, of either the suppressor or helper type. Despite the common property of reacting with anti-Ia antisera, the two sets of factors differ by many criteria. Macrophages, upon culture with antigen, release complexes of Ia antigen and a fragment of the original immunogen. This material is only produced by responder macrophages and thus appears to be a soluble Ir gene product. The genetic restriction of the T-macrophage interaction was investigated in chimeras, and it was found that the host environment as well as the donor genotype was of importance in determining restrictions, which were thus not really directed to "self." There was no evidence for intrinsic T-cell Ir genes, as nonresponder stem cells developed into responder T-cells in a (responder X nonresponder) F1 environment. However, these cells only responded in the presence of responder macrophages. Specific T-cell factors are different in nature. These all react with anti-Ia antisera, but the nature or function of the T-cell Ia is unknown. The basic structure involves a VARIAble region" responsible for antigen binding which, as it reacts with anti-idiotype antisera and anti-variable region framework antisera is an immunoglobulin variable region. There is also a "constant region," defined by its biological properties as well as by specific rabbit antisera. This two-region nature of specific factors is reminiscent of immunoglobulin structure and it is a reasonable hypothesis that the constant region is linked to the Ig cluster of genes