Recent findings suggest that maternal vitamin D insufficiency during pregnancy has consequences for the offspring's bone health in later life. To investigate whether maternal vitamin D insufficiency affects fetal femur growth in ways similar to those seen in childhood rickets and study the timing during gestation of any effect of maternal vitamin D status, we studied 424 pregnant women within a prospective longitudinal study of maternal nutrition and lifestyle before and during pregnancy (Southampton Women's Survey). Using highresolution 3D ultrasound, we measured fetal femur length and distal metaphyseal cross-sectional area, together with the ratio of femoral metaphyseal cross-sectional area to femur length (femoral splaying index). Lower maternal 25-hydroxyvitamin vitamin D concentration was not related to fetal femur length but was associated with greater femoral metaphyseal cross-sectional area and a higher femoral splaying index at 19 weeks' gestation [r ¼ À0.16, 95% confidence interbal (CI) À0.25 to À0.06 and r ¼ À0.17, 95% CI À0.26 to À0.07, respectively] and at 34 weeks' gestation (r ¼ -0.10, 95% CI À0.20 to 0.00 and r ¼ À0.11, 95% CI À0.21 to À0.01, respectively). Three groups of women were identified with 25-hydroxyvitamin vitamin D concentrations that were sufficient/borderline (>50 nmol/L, 63.4%), insufficient (25 to 50 nmol/L, 30.7%), and deficient ( 25 nmol/L, 5.9%). Across these groups, the geometric mean femoral splaying indices at 19 weeks' gestation increased from 0.074 (sufficient/borderline) to 0.078 (insufficient) and 0.084 (deficient). Our observations suggest that maternal vitamin D insufficiency can influence fetal femoral development as early as 19 weeks' gestation. This suggests that measures to improve maternal vitamin D status should be instituted in early pregnancy. ß

The thermic effect of 1.67 MJ (400 kcal) of carbohydrate (glucose), fat, protein and mixed meal were examined in 11 lean and 11 obese subjects by indirect calorimetry. The changes in metabolic rate in response over 90 min period (30-120 min after the meal) to the different meals were compared with that seen after a similar volume of low calorie drink. The thermic effects of glucose and protein were not significantly different between lean and obese subjects. Obese subjects showed very little increase in metabolic rate following ingestion of fat (-0.9 +/- 2.0%, mean +/- SEM) and this was significantly different from that seen in lean subjects (14.4 +/- 3.4%). The thermogenic response to mixed meal was also significantly lower in obese subjects when expressed as percentage change (12.9 +/- 2.3% compared to 25.0 +/- 4.8%). There was no evidence for delay in gastric emptying times for glucose and fatty meal in the six obese subjects in whom these were measured. We conclude that obese subjects show a reduced thermogenic response to fat.

Follow-up of recurrent differentiated thyroid carcinoma involves the measurement of serum thyroglobulin (Tg). However, Tg autoantibodies are present in a high proportion of thyroid carcinoma patients (up to 25%) and these can interfere with the Tg immunoassays. To overcome this obstacle, investigators have used real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to measure Tg mRNA in the blood of patients with differentiated thyroid cancer, with varying degrees of success. In the present study, we demonstrate the first reported use of the PAXgene Blood RNA collection tube and extraction kit method for the preparation of RT-PCR-quality RNA with subsequent deployment of the latter in the development of a specific, sensitive, and reproducible Taqman assay for the detection and quantification of thyroglobulin mRNA. Beta-actin mRNA was also assayed and results are expressed as a ratio of Tg to beta-actin mRNA. The intra-assay coefficient of variations (CVs) for Tg and beta-actin mRNA assay were 27.7% and 25.4%, respectively. Inter-assay CVs were 20.8% and 28.8%, respectively, for the two assays. Tg mRNA was detected in all cancer subjects (n = 42) and healthy individuals (n = 20). Tg mRNA was significantly higher in cancer patients than in the healthy subjects (0.00169 +/- 0.00013 vs. 0.00051 +/- 0.00015; P<0.0001). Fourteen cancer patients had detectable levels of serum Tg, and Tg mRNA levels tended to be higher in these than in cancer subjects with undetectable serum Tg (0.00188 +/- 0.00021 vs. 0.00157 +/- 0.000178; P = 0.08). Circulatory Tg mRNA measurement may serve a useful role in the assessment of thyroid cancer.

SUMMARY Our earlier observation that pentagastrin is a calcitonin (CT) secretagogue was confirmed and extended to include both synthetic human gastrin I and pure porcine gastrin II. The latter hormone was shown to stimulate the secretion rate of CT from thyroid preparations perfused in situ in anaesthetized pigs at concentrations (0·5 nmol/l) similar to those found after stimulation of gastrin production by a meat extract placed in the stomach (0·2 nmol/1). These concentrations of plasma gastrin are considerably less than those found in man in both pernicious anaemia and the Zollinger—Ellison syndrome, whereas the mean fasting plasma gastrin concentrations in normal human beings and pigs are similar. It is suggested that the comparatively high incidence of parathyroid hyperactivity in association with the Zollinger—Ellison syndrome may be a consequence of an increased CT secretion rate induced by hypergastrinaemia. Furthermore, the existence of a gastrointestinal—thyroid C cell system is proposed as an integral part of postprandial calcium homeostasis.

The role of calcitonin (CT) in postprandial calcium homeostasis and the possibility of a gastroentero-thyroid C-cell system was studied in young pigs. When pigs were fasted for more than 36 h and then fed, the plasma calcium concentration decreased by 6\m=.\1 % over a period of 60\p=n-\120 min after a meal. Since in thyroidectomized pigs the plasma calcium concentration increased by 7\m=.\2 % when they were fed after a fast of 36 h it is suggested that increased CT secretion assists in the control of postprandial hypercalcaemia. Direct measurement of CT in peripheral plasma supported this suggestion. Because the plasma calcium concentration in an intact pig on a normal feeding regime does not change after a meal, the possibility of the involvement of one or more humoral factors in the stimulation of thyroid C-cells was investigated. Exogenous gastrin and endogenous gastrin stimulated by meat extract were both previously shown by us to increase CT secretion rate. This observation has now been extended to include other stimuli to endogenous gastrin, e.g. glycine and gastric distension. Furthermore, partially purified enteroglucagon increased CT secretion rate from perfused thyroid glands, isolated in situ. Stimulation of endogenous entero\x=req-\ glucagon by the intraduodenal administration of glucose, and probable stimulation of endogenous pancreozymin by intraduodenal fat, were both associated with an increased CT secretion rate from the thyroid gland.These results support the concept of a gastroentero-thyroid C-cell system which serves to stimulate CT secretion and thus to protect the skeleton from excessive bone resorption during periods of dietary sufficiency.