SUMMARY Parathyroid hormone and calcium were measured in plasma taken from pregnant women at term and from the umbilical veins of their infants at birth. Three assays were used to measure parathyroid hormone, a cytochemical bioassay of bioactivity and two immunoradiometric assays, one specific for the amino terminus, the other specific for the carboxy terminus of the parathyroid hormone molecule.Plasma calcium was significantly higher in the infants than in the mothers. Maternal parathyroid hormone bioactivity and the amino terminus were both slightly raised, but the carboxy terminus value was normal; these findings supported the view that late pregnancy is a time of mild physiological hyperparathyroidism. In the infants, the amino terminus was undetectable and the carboxy terminus was either undetectable or towards the lower end of the normal range: bioactivity of parathyroid hormone was considerably raised and was related to the gradient of calcium across the placenta. This suggests that the parathyroid glands are not suppressed during fetal life and that they may play an important part in the maintenance of high fetal plasma calcium concentrations.It has long been recognised that the total concentration of calcium in maternal plasma falls during pregnancy, particularly during the last trimester
Four weight reduction strategies were investigated in a diabetic population who previously had shown little motivation to lose weight. Some 409 patients, body mass index 28-45 were invited to participate. Only 51% replied, although 22 patients (5.4%) lost > 3 kg by invitation alone. The study comprised 159 patients, randomly allotted to either regular clinic visits, behavioural group therapy, dexfenfluramine (30 mg d-1 for initial 3 months) or combined home and clinic visits. A further 58 patients were monitored as controls. At 3 months the best weight loss (intention to treat) was achieved using dexfenfluramine with mean weight losses of 1.6, 1.2, 3.4, and 1.7 kg, respectively, in each group. At 1 year weight losses were similar (1.2, 1.8, 2.8, 1.2 kg, respectively) but contrasted with a mean 1.2 kg weight gain in the controls. Some 38% lost > 3 kg on dexfenfluramine compared to 19-23% for the others. In those who completed the study, weight loss was similar with behavioural therapy (3 kg) or dexfenfluramine (3.2 kg). We conclude that intensive dietetic efforts can reverse the weight increase in the diabetic population although weight loss is minimal. Dexfenfluramine was most effective in the short term, behavioural therapy useful long term but only in those who remained within the group; home visits offered no advantage.
Circulating immunoreactive parathyroid hormone (PTH) was measured by a homologous, amino-terminal, specific, immunoradiometric assay in man. In forty-two healthy subjects the concentrations ranged between < 40 pg/ml and 120 pg/ml. No hormone could be detected in the sera of eleven patients with hypoparathyroidism, but the concentrations were clearly elevated in six patients with pseudohypoparathyroidism (range 190-1120 pg/ml). In thirty-five patients with primary hyperparathyroidism the mean (+/- SEM) concentration was 283.4 +/- 42.4 pg/ml (range 100-1350 pg/ml). A significant positive correlation was demonstrated between immunoassayable hormone and serum calcium concentrations in these patients. In nine patients PTH concentrations were measured before and after parathyroidectomy. In all of them they were elevated pre-operatively but fell to the normal range after parathyroidectomy. The disappearance of exogenously administered synthetic human PTH (1-34) from the circulation of two normal subjects was rapid with an apparent plasma half-disappearance time (t1/2) between 2 and 3 min; the metabolic clearance rate was 12.9 and 9.0 ml. kg-1 . min-1 respectively. Similarly, the disappearance of endogenous, amino-terminal, immunoreactive PTH from the circulation of two patients with primary hyperparathyroidism after parathyroidectomy was rapid; the apparent t1/2 was approximately 3 min. Homologous amino-terminal specific immunoassays for PTH can thus be useful for the study of both the acute, and chronic, changes of circulating hormone in man and represent an improvement over heterologous unselected assay systems.
Weight change and glycaemic control in 132 diabetic patients previously treated for 1 year by four different methods aimed at weight loss were reanalysed 4 years after the outset. The four treatment groups comprised clinic visits, home visits, behavioural group therapy, and dexfenfluramine given for the initial 3 months followed by clinic visits. When analysed on an intention to treat basis only the dexfenfluramine group maintained a significant weight loss at year 4 (mean -2.46 kg) with 43% of patients losing 3 kg or more; HBA1c was not decreased. The other treatment groups showed overall weight regain from year 1 to year 4. Within the home visit group however, the number of patients losing at least 3 kg doubled between years 1 (21%) and 4 (38%). When analysed on a completion basis, weight loss in the dexfenfluramine group was significant in females but not in males at year 4. During the 4 years of observation a cohort of 54 patients reflecting our routine clinic practice gained on average 0.35 kg. Although now withdrawn, the use of an appetite suppressant dexfenfluramine for just 3 months would appear to have a long-term advantage on weight loss in this diabetic population, although the weight lost was not associated with improvement in glycaemic control.
SUMMARYAn homologous carboxy‐terminal specific immunoradiometric assay for human parathyroid hormone (PTH) has been developed which uses an antiserum raised in a goat against intact human PTH. This assay has been applied to the measurement of circulating PTH in man; the reference preparation was a 53–84 fragment prepared from native human parathyroid hormone. PTH was detectable in all the normal subjects studied (range 0·1–0·79 ng/ml) and elevated concentrations were found in a group of patients with primary hyperparathyroidism (range 0·82–25·5 ng/ml). Carboxy‐terminal hormone concentrations were particularly raised in uraemic subjects (range 1–02–52–5 ng/ml) but some patients with vitamin D deficient osteomalacia had concentrations within the normal range (0·5–2·4 ng/ml). All patients with pseudohypoparathyroidism had elevated concentrations (range 1·0–2·8 ng/ml) and in patients with idiopathic or surgical hypoparathyroidism the concentration ranged from undetectable to 0·4 ng/ml. These results have been compared with those obtained using an amino‐terminal specific assay. In normal subjects carboxy‐terminal immuno‐reactive hormone concentrations were, on average, three times higher than those measured in the amino‐terminal assay (C:N ratio 3·28). In patients with secondary hyperparathyroidism this ratio was dependent on renal function and the plasma calcium concentration. The disappearance of endogenous carboxy‐and amino‐terminal PTH from the circulation of a patient with primary hyperparathyroidism was studied. Amino‐terminal reactive PTH disappeared much more rapidly (t½= 1·5 min) than carboxy‐terminal hormone (t½= 2·75 h). It is hoped that the carboxy‐terminal specific assay described here will be of value in the further study of the secretion and metabolism of PTH.
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