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11 the severity of the clinical symptoms could not be adequately explained by valvular regurgitation, of which there was little evidence on examination of the heart. Blood cultures usually remained sterile, presumably because of inappropriate antibiotic treatment or the limited infectiveness of the organisms present, or both.A striking feature in three patients (cases 1, 2, and 4) was the acute, severe, and rapidly resolving but recurrent episodes of pulmonary oedema. Possibly these were caused by sudden blocking of the orifice by -vegetation-this was indeed shown echocardiographically in one patient (case 4). Other patients (cases 3 and 5 and those reported by Reeve et all and Matula et al2) had more progressive pulmonary oedema, suggesting increasing mitral stenosis. In our experience both types of pulmonary oedema are uncommon in patients with isolated mitral valve regurgitation during bacterial endocarditis.Those of our patients who did not have mitral valve replacement (cases 2, 4, and 5) and the patient of Reeve and his colleagues' had a sudden cardiac arrest. Mitral valve vegetations cause obstruction just as catastrophic as an atrial tumour or a ball thrombus, and hence once the doctor suspects mitral valve obstruction he should confirm the diagnosis promptly and ensure that the patient is rapidly operated on.Accurate diagnosis is vital. Right heart catheterisation showed a raised pulmonary wedge pressure without a striking V wave, but was nevertheless of little value in assessing the severity of the haemodynamic disturbance: pressures may be very high because of rheumatic valve disease (case 4) Journal, 1978, 1, 11-14 Summary and conclusions Thirty-five children known to have had respiratory syncytial virus bronchiolitis in infancy were examined at the age of 8 and their respiratory function tested. The results were compared with those in 35 controls matched for age, sex, and social class. Although 18 of the children who had had bronchiolitis in infancy had experienced subsequent episodes of wheezing, these were neither severe nor frequent in most cases and had apparently ceased by the age of 8. Nevertheless, the mean exercise bronchial lability of the children who had had bronchiolitis was significantly higher than that of the control children and the mean peak expiratory flow rate at rest significantly lower.

A new procedure for measuring patient serum thyrotropin receptor (TSHR) autoantibodies is described in which the autoantibodies inhibit binding of a human monoclonal thyroid stimulating antibody M22 (labeled with biotin) to TSHR-coated enzyme-linked immunosorbent assay (ELISA) plate wells. In the assay, M22-biotin binding is detected by addition of streptavidin peroxidase. The M22 based assay was more sensitive than a similar ELISA based on inhibition of TSH-biotin binding to TSHR coated wells with 1 U/L of NIBSC 90/672 giving approximately 35% inhibition in the M22-based system compared to approximately 15% inhibition in the TSH-based ELISA. This had an important impact on the precision of the 2 assays with the M22-based ELISA showing an interassay coefficient of variation (CV) of 10% at 1 U/L whereas the TSH-based ELISA had an interassay CV of 20% at 1 U/L. Analysis of sera from 307 control subjects without a diagnosis of Graves' disease indicated that only 2 (0.65%) gave inhibition of M22 binding values of greater than 10% (11% and 12% inhibition). In the case of sera from 108 patients with Graves' disease (treated and untreated) 103 (95%) gave inhibition of M22 binding values of 14% or greater. Receiver operating characteristic (ROC) plot analysis showed that 100% specificity for TSHR autoantibody detection in Graves' disease was obtained at 95% sensitivity for the M22-based ELISA and 89% sensitivity for the TSH-biotin-based ELISA. Inhibition of M22 binding to the TSHR was closely correlated to inhibition of TSH binding in the 108 Graves' sera (r = 0.99). However, inhibition of M22 binding was almost always greater resulting in improved sensitivity and precision.

SUMMARY.— The incidence of thyroid disease in patients with alopecia areata was greater than in patients with psoriasis and also greater than in a control series of the general population. There was also an increased incidence of alopecia areata and diabetes mellitus in the relatives of patients with alopecia areata. No significant difference was found in the incidence of thyroglobulin and thyroid complement‐fixing antibodies in patients with alopecia areata as compared with a general practice population. A negative association between psoriasis and thyroid antibodies was demonstrated.

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Graves' disease is an autoimmune disorder but the nature of the association between hyperthyroidism and ophthalmopathy is not yet understood. Serum autoantibodies to orbital tissues have previously been identified and the cross-reactivity with orbital and thyroid antigens has been implicated in the development of thyroid-associated ophthalmopathy (TAO). The ophthalmopathy of Graves' disease is remarkable for the hypertrophy of extraocular muscles and proliferation of fibroblasts within the orbit; features which suggest a possible involvement of growth factors. The present study was therefore undertaken to investigate the interaction of IgGs extracted from the sera of patients with Graves' disease, with or without overt ophthalmopathy, with respect to IGF-1 receptor binding sites on fibroblasts from human orbital tissue. IGF-1 binding sites were demonstrated on human orbital fibroblast monolayers grown from eye muscle explants. These cells exhibited a population of high affinity IGF-1 binding sites (Kd, 0.5nM SEM +/- 0.05). IgG prepared from sera taken from patients with Graves' disease (n = 23) significantly inhibited [125I]IGF-1 binding to orbital fibroblasts when compared to IgGs prepared from normal volunteers (n = 13, p < 0.002). It was found that 12 of 23 (52%) patients' IgG samples gave rise to significant levels of inhibition of [125I]IGF-1 binding to orbital fibroblasts. The IgG preparations did not bind directly to IGF-1. This study demonstrates that IgG prepared from patients with Graves' disease with or without overt ophthalmopathy interact with IGF-1 binding sites on orbital fibroblasts whereas IgG from normal subjects had no significant effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Using a sensitive and precise radioimmunoassay for human TSH we have demonstrated significant elevations in serum TSH levels in euthyroid volunteers following administration of the dopamine receptor blocking drug metoclopramide when compared with placebo. The degree of TSH response is significantly greater in females than in males and is sustained over a 3-hour period after a single oral 10 mg dose of metoclopramide. The degree of TSH release after metoclopramide is inversely related to the basal TSH level suggesting that dopamine is a determinant of low daytime TSH levels and is thus implicated in the circadian rhythm of TSH secretion. Pretreatment with 10 mg of metoclopramide orally, one hour before TRH administration leads to significant enhancement of the TSH response to TRH. Our findings provide further evidence for the physiological inhibitory role of dopamine in the contol of TSH secretion in normal man. The possible mode of action of dopamine and the clinical implications of this neuroregulatory pathway are discussed.