Assessment of a point-of-care test for paracetamol and salicylate in blood.

BACKGROUND: Paracetamol and salicylate are commonly taken in acute overdose. Clinicians have a low threshold for excluding the presence of these two drugs, by ordering laboratory tests in any patient suspected of ingesting an overdose or with an altered mental state. AIM: To test the effectiveness of a new point of care test that qualitatively detects paracetamol and salicylate in blood and to examine the potential time saved by its use. DESIGN: Prospective multicentre trial. METHODS: The new test was compared with laboratory analysis in a routine blood sample taken from patients presenting to emergency departments with suspected overdose. RESULTS: The test had sensitivities of 98.5% and 88.5%, and specificities of 74.7% and 92%, for paracetamol and salicylate, respectively, at cut-off levels of 25 mg/l and 100 mg/l, respectively The point of care test results were available 2 h before the laboratory result. DISCUSSION: This point-of-care test could be used to rule out an overdose with either of these two drugs, and could thus lead to earlier clinical decisions for suspected overdose patients. Recommendations have been made following this trial that the cut-off value for paracetamol should be reduced from 25 mg/l to 12.5 mg/l in order to increase its usefulness. To prevent the test being misread, we also suggest that each device should be embossed to remind users that the presence of a line indicates there is no drug present.

Identification of the antigen recognized by the monoclonal antibody BU31 as lamins A and C.

The murine monoclonal antibody BU31 binds to the nuclear membrane of many cell types. The expression of the BU31 antigen has previously been shown to have an inverse correlation with the proliferative index in lung tumours, defined by Ki67 staining. The distribution of BU31-positive cells is now shown to parallel the distribution of non-dividing cells in a range of normal human and rat tissues, although neuroendocrine cells and germ cells in the testis show no reactivity. Cells grown in culture and induced to undergo growth arrest show a higher level of labelling with BU31 than their proliferating counterparts. Confocal laser scanning microscopy reveals that the BU31 antigen is distributed predominantly along the nuclear lamina, with occasional internal foci. This distribution is very similar to that of the nuclear membrane proteins lamin A and lamin C, suggesting that the BU31 antigen and lamins A and C could be one and the same. Immunoblotting using recombinant lamin proteins confirmed this proposal. Moreover, a monoclonal antibody to the non-proliferation-associated antigen, statin, also recognizes lamins A and C. These data indicate that the demonstration of lamins A and C can be used to provide information on the proliferative activity of normal and neoplastic tissues. These data also suggest a role for nuclear lamins A and C during cellular quiescence, possibly through the reorganization and maintenance of nuclear structure, or more directly through interactions with the retinoblastoma gene product or related proteins.

Endocrine cells of the human gastrointestinal tract have no proliferative capacity.

There is compelling evidence that the epithelial cell lineage of the gastrointestinal tract are derived from a common stem cell precursor, but the details of the subsequent cellular hierarchies remain uncertain. In this context, it is important to know the arrangement of cell proliferation that gives rise to the final cell populations. In rodents, a number of studies have been performed examining the possible proliferative capacity of endocrine cells, but a wide range of technical problems makes interpretation of these data difficult. Continuous labelling studies suggest there is potential for proliferation in endocrine cells but flash labelling studies have not been conclusive. In man there are no data on this issue. We have taken advantage of the ability to perform double immunostaining for operational markers of proliferation (Ki67 antigen) and endocrine cell phenotype (chromogranin expression). We demonstrate that there are no double-labelled cells in the normal stomach, small intestine or colon of fetal, neonatal or adult humans. Moreover, no double-labelled cells are found in pathological states associated with endocrine cell hyperplasia (gastritis, ulcerative colitis). These data indicate that the normal endocrine cells of the human gut have no proliferative capacity and that, in this cell lineage, population expansion precedes differentiation.