Comparison of the use of Tanner and Whitehouse, NCHS, and Cambridge standards in infancy

The British (Tanner and Whitehouse) and American (National Center for Health Statistics, NCHS) growth standards are widely used internationally, although the data are now over 30 years old. Routine weight data was retrieved from the child health records of a complete annual cohort of 3418 children aged 18-30 months to test the validity of these standards for modern infants. Compared with the Tanner and Whitehouse standards, Newcastle children rose initially and then fell a mean of 0.7 SDs between 6 weeks and 18 months, resulting in a threefold difference in the proportion of children below the 3rd centile at different ages. NCHS standards showed a similar pattern. When compared with modern standards from the Cambridge growth study, there was a much closer match, although Newcastle children showed a slight gain by the age of 1 year. Existing standards for weight introduce inaccuracy into the estimation of centile position in the early months of life. As both standards show similar problems this probably represents a real secular change due to changes in infant nutrition. These findings support the need to develop new national growth reference standards.     

Antibodies that promote thyroid growth. A distinct population of thyroid-stimulating autoantibodies

We used a strain of differentiated rat-thyroid cells in continuous culture (the FRTL-5 strain) to detect the presence of growth-promoting antibodies in serum samples from patients with autoimmune thyroid disease. We found that IgG preparations from 17 of 20 patients (85 per cent) with active Graves' disease and two of five patients (40 per cent) with Hashimoto's thyroiditis could augment thyroid-cell growth. In parallel with IgG-induced elevations in intracellular cyclic AMP levels in the same cell line, all 20 of the patients with active Graves' disease had thyroid-stimulatory antibodies. Patients' IgG preparations fell into three subclasses: those with both potent cyclic AMP stimulation and potent growth-promoting activity; those with potent cyclic AMP stimulation but low-level growth promotion; and those with potent growth promotion and low-level cyclic AMP action. Growth-promoting antibodies were not detected in patients with Graves' disease in remission (seven patients), nodular goiter (seven), subacute thyroiditis (five), or atrophic thyroiditis (one). Simultaneous assays of growth promotion and cyclic AMP stimulation may be useful in the care of patients with autoimmune thyroid disease.     

Calf serum modifies the mitogenic activity of epidermal growth factor in WRT thyroid cells

It has already been shown that Wistar rat thyroid (WRT) cells in low concentrations of calf serum (0.5%) are under the influence of both thyrotropin (TSH) and insulin as regards growth. The present data show that epidermal growth factor (EGF), in concentrations up to 10 micrograms/ml, is not able to modify DNA synthesis in WRT cells. On the other hand, insulin-like growth factor I (IGF-I) stimulates DNA synthesis from a dose which is 10-fold lower than that of insulin alone. Combined stimulation of EGF and TSH in WRT cells is equal to that of TSH alone in relation to DNA synthesis, while the combined presence of TSH and IGF-I, or TSH and insulin, in the same medium results in an effect which is greatly superior to the theoretical sum of activities. Repetition of the same experiments using the original clone of WRT cells, but in high concentrations of calf serum (5%), shows that EGF stimulates DNA synthesis in a dose-dependent way from 0.1 to 100 ng/ml. Under these conditions, combined stimulation of EGF with TSH shows that DNA synthesis is equal to the predicted theoretical sum. No other differences in WRT cell sensitivity to either IGF-I or insulin, or IGF-I and TSH and insulin and TSH, can be noted. This finding is confirmed by the demonstration of specific and sensitive binding sites for EGF on WRT cells cultured in 5% calf serum; these binding sites are not present on WRT cells adapted to grow in 0.5% calf serum. Present data support the hypothesis that EGF and serum growth actions are mediated through the same analogous pathway, which is, however, different from those of TSH and/or IGF-I and/or insulin.     

Monoclonal antibodies to the thyrotropin receptor: the identification of blocking and stimulating antibodies

Monoclonal antibodies to the thyrotropin (TSH) receptor have been obtained from fusions of mouse myeloma cells with spleen cells immunized with solubilized thyroid membrane preparations. Two monoclonal antibodies which inhibit 125I-TSH binding and are reactive with the glycoprotein component of the bovine TSH receptor (11E8 and 13D11), are shown to inhibit basal and TSH stimulated adenylate cyclase activity in bovine thyroid membranes and human thyroid cells. Both antibodies also inhibit 125I-TSH binding in vitro, whether binding is measured at pH 6.0 in low salts and at 0-4 C or at pH 7.4 in 50 mM NaCl and at 37 C. The glycoprotein component is thus a portion of the physiologic TSH receptor in vivo and 125I-TSH binding studies apparently measure the high affinity glycoprotein component under nonphysiologic conditions and conditions more representative of the physiologic milieu. A third monoclonal antibody whose interaction with thyroid membranes is prevented by TSH is shown to stimulate adenylate cyclase activity in bovine thyroid membranes and human thyroid cells. This stimulating antibody only weakly inhibits 125I-TSH binding to thyroid membranes or to the glycoprotein component of the TSH receptor. The 22A6 antibody does, however, immunoprecipitate mixed brain gangliosides, in distinct contrast to the monoclonal antibodies to the glycoprotein receptor component, i.e., 11E8 and 13D11. The results support the speculation that autoimmune antibodies which inhibit TSH binding to thyroid membranes are not necessarily identical to antibodies which stimulate function; that antibodies directed at the high affinity initial site of TSH interaction with a cell can behave as blocking rather than stimulating antibodies and that a possible relationship exists between stimulating antibodies and the low affinity TSH binding sites (gangliosides) on thyroid membranes.     

LORAZEPAM IN STUPOR

SUMMARY The use of lorazepam in relieving catatonic symptoms is illustrated by the dramatic response in a stuporous patient. The treatment allows further investigations and management. It is recommended that clinicians familiarise themselves with this simple pharmacological intervention.