This review examines broad issues of concern regarding the primary/secondary care interface. The main purpose was to identify areas of good practice which could be adapted for more general use. One of the most fundamental aspects identified was communication, which is discussed in some detail. Also covered are shared prescribing and disease management. The data suggest that the most effective system(s) of shared care has yet to be established. Further qualitative and economic evaluations are required, taking into account patient preferences. Although the literature does describe certain practice exemplars, it is clear that inter- and intra-professional communication continues to be a problem. Whilst information technology may provide some of the solutions, it is concluded that a culture change, which compels health professionals to make sharing of patient information a much higher priority, is required.

1. IgG, IgM and IgE anti‐benzylpenicilloyl (BPO) antibody activities were determined by enzyme‐linked immunosorbent assay (ELISA) in sera from 100 patients who claimed to be allergic to penicillin, and from 50 healthy volunteers. Continuous frequency distributions for all three classes of anti‐BPO antibody, defined as differential binding (delta OD) to BPO‐human serum albumin (HSA) and HSA, were obtained for both groups. 2. For IgM and IgE classes the anti‐BPO activities were slightly but statistically significantly higher in the patient group compared with the volunteer group. 3. Hapten inhibition ELISAs were performed to confirm specificity for the BPO determinant. On the basis of antibody activities (delta OD values) greater than or equal to 0.3 and 50% inhibition of binding in the presence of 100 micrograms ml‐1 BPO‐caproate, BPO‐specific IgG antibody was identified in 4/100 of the patients' sera and in 1/50 of the volunteers' sera; BPO‐specific IgM was identified in 7/100 patients' sera and 1/50 volunteers' sera; and BPO‐specific IgE in 5/100 patients' sera and 1/50 volunteers' sera. 4. Not all sera with differential antibody binding to BPO‐HSA/HSA were inhibited by the BPO hapten. Hence, hapten inhibition assays are essential for the unambiguous demonstration of drug specific antibodies.

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Transforming growth factor beta (TGF beta) suppresses the growth of differentiation inducible, murine IL-3-dependent multipotential cell lines but has no growth inhibitory effect upon an IL-3-independent (leukaemic) cell line arising from one of them, nor on IL-3-dependent cell lines that are unable to undergo differentiation. TGF beta inhibits in vitro colony formation by normal multipotential haemopoietic progenitor cells. Bipotential progenitors recruited by GM-CSF are, however, more resistant to the inhibitory effects of TGF beta, whereas progenitors recruited by the lineage restricted factor, M-CSF, are sensitive to the inhibitory effects. These data indicate that responsiveness to TGF beta is differentiation linked and studies with the cell lines suggest that response (or lack of response is not determined solely by levels of expression of TGF beta receptors. Furthermore, the effects of TGF beta 2 on haemopoietic progenitors are very similar to those induced by TGF beta.

Interleukin-3 (IL-3) dependent multipotent haemopoietic stem cells FDCP-Mix A4 (A4) were induced to differentiate and develop into mature neutrophils in response to Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) plus granulocyte CSF (G-CSF). This resulted in an increase in cell number over seven days of culture, following which the cells lost the ability to undergo further proliferation. The effect of GM-CSF on these cells has been assessed at various stages of development. Clonogenic cells, able to respond to GM-CSF, were generated only at days 3, 4 post-induction. From day 5 onwards, mature post-mitotic neutrophils are produced and clonogenic cells are lost. Loss of proliferative potential, in response to GM-CSF, was confirmed using [3H]-thymidine incorporation. Receptors for GM-CSF, were also measured during development using [125I]-GM-CSF binding assays. Although the dissociation constant for GM-CSF binding sites did not vary considerably, the number of such sites increased dramatically from about 20 (day 0, when the cells have a primitive morphology) to about 1000 by day 6 (when the cells are predominantly mature neutrophils). GM-CSF-stimulated Na+/H+ antiport activation was also determined. Although few GM-CSF receptors are expressed at day 0, there is a significant response (63% of maximal) to GM-CSF in terms of intracellular alkalinisation: this response increased markedly until, by day 4 (700 GM-CSF binding sites/cell), there is a maximal activation of the antiport by GM-CSF. By day 7 (greater than 900 GM-CSF binding sites/cell), however, there is significant reduction in activation of the Na+/H+ antiport by GM-CSF. Nonetheless, increased viability of these mature cells is still seen in response to GM-CSF. These results suggest that not only does expression of GM-CSF receptors alter during development of multipotential cells to mature neutrophils, but that these receptors are coupled to different intracellular effector mechanisms as the cells progressively mature.