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We describe a method for estimating hemoglobin A1c (HbA1c) with a commercially available enzyme immunoassay system. The method is based on microtiter plate technology, utilizing an antibody raised to hemoglobin, the epitope being the Amadori product of glucose plus the first eight amino acids on the N-terminal end of the beta chain of hemoglobin. The enzyme immunoassay displays good within-batch (CV 2.3-2.4%) and between-batch (CV 2.6-5.0%) precision, and the results were not affected by different types of anticoagulant. The method was linear within the expected range of results and showed good correlation (r = 0.88-0.98) with established methods for estimating glycohemoglobin. Using this method, we obtained a reference interval of 2.8-4.9% (central 95%) for HbA1c in a nondiabetic population. The percentages of hemoglobin that were HbA1c in diabetics (6.86% +/- 2.51%) were significantly greater (P < 0.001) than in nondiabetics (3.46% +/- 0.52%).

Plasma von Willebrand factor, plasminogen activator inhibitor activity and C-reactive protein were assessed as markers of coronary recanalisation in 30 patients with acute myocardial infarction receiving tissue-type plasminogen activator (t-PA). Blood samples were taken before t-PA (time 0), 4-hourly for 24 h and daily up to 72 h. A continuous electrocardiogram was recorded in the first 24 h. Coronary arteriography was performed 90 min and 24 h after the start of t-PA. Patients with a patent infarct artery (n = 17), compared to those with occluded artery (n = 13), showed a fall in von Willebrand factor from 0 to 24 h (p = 0.001), a greater fall in plasminogen activator inhibitor from 24 to 48 h (p = 0.04) and a fall in C-reactive protein from 48 to 72 h (p = 0.002). The accuracy of these indices compared favourably with time to peak plasma MB creatine kinase and > or = 50% resolution of maximal ST-deviation on the electrocardiogram. Thus, changes in plasma von Willebrand factor, plasminogen activator inhibitor and C-reactive protein during the first 3 days of myocardial infarction are indicative of thrombolytic efficacy. Their concordant behaviour may reflect a common regulatory mechanism.

1. To examine the metabolic effects of increases in circulating endogenous plasma catecholamines, we measured plasma glucose, potassium and magnesium in 14 patients undergoing elective coronary artery bypass grafting. The patients were randomized into two groups and received either sodium nitroprusside (a direct-acting vasodilator) or trimetaphan camsylate (a ganglion-blocking agent) for routine control of blood pressure during the operation. 2. There were significant differences between the two groups in the levels of all three metabolic variables studied. Plasma glucose levels rose in both groups, but were significantly higher in the sodium nitroprusside group [peak levels 9.14 (SEM 0.72)mmol/l compared with 6.71 (0.88) mmol/l, P less than 0.001, analysis of variance]. The cardioplegia solution caused a large increase in plasma magnesium in both groups but in the sodium nitroprusside group the level rose higher [to 1.59 (0.12)mmol/l compared with 1.34 (0.06)mmol/l] and fell faster (P less than 0.05, analysis of variance). In the group receiving sodium nitroprusside, plasma potassium fell, by a mean of 0.34mmol/l, as plasma catecholamine levels rose; no such fall was seen in the group receiving trimetaphan camsylate (P less than 0.05, analysis of variance). 3. It is concluded that the sympathoadrenal system is important in causing metabolic changes during cardiopulmonary bypass and may be relevant in other conditions such as acute myocardial infarction.

Tumors associated with the Verner Morrison syndrome secrete peptide histidine methionine, its C-terminally extended variant peptide histidine valine, and vasoactive intestinal peptide. There is evidence that vasoactive intestinal peptide mediates diarrhea, but recent evidence suggested that peptide histidine methionine and peptide histidine valine may be at least as important. Infusion of vasoactive intestinal peptide, peptide histidine methionine, and peptide histidine valine into patients with ileostomies produced mean plateau plasma levels of 163, 1301, and 2106 pM, respectively, which are within the range seen in the Verner Morrison syndrome. Vasoactive intestinal peptide produced an integrated ileal output of 174 (53) g (mean [SEM]), compared with only 20 (7) g with peptide histidine methionine and 10 (3) g with peptide histidine valine. These results suggest that vasoactive intestinal peptide is substantially more important than peptide histidine methionine or peptide histidine valine in mediating diarrhea in the Verner Morrison syndrome.

Amylin is a new member of the calcitonin/CGRP family: it is a 37 amino acid polypeptide which was recently isolated from amyloid deposits in pancreatic islets obtained from type II diabetics. In the present study we investigated the effect of amylin and amylin-amide on calcium metabolism in the rat and rabbit. Two main methods were used: in vivo hypocalcaemic activity was assessed by measuring plasma calcium levels after injection of the peptide in 50 g rats; and in vitro resorption of cortical bone by disaggregated rat osteoclasts was quantified by scanning electron microscopy together with image analysis. We demonstrate that amylin and amylin-amide have calcitonin-like effects: both are powerful inhibitors of osteoclastic resorption and as a consequence lower plasma calcium in both rats and rabbits. We speculate that the peptide may exert systemic or local regulatory effects on bone cells.

The calcitonin-calcitonin gene-related peptide (CGRP) gene complex encodes a family of novel peptides--calcitonin, CGRP and katacalcin. Whereas calcitonin is a circulating hormone involved in skeletal maintenance, the physiological function of CGRP still remains unclear. In the present study we have compared the biological activity of CGRP with that of calcitonin using three experimental systems. We have demonstrated that both peptides inhibit bone resorption by active rat osteoclasts and thus lower plasma calcium when injected into young rats. In both respects the CGRP homologues (rat, human alpha and human beta) were found to be 100- to 1000-fold less potent than human calcitonin. The effects of the CGRP peptides and calcitonin were only additive. Human CGRP (alpha) also caused a marked dose-dependent elevation of bone cyclic AMP levels in mice, somewhat like calcitonin. Though from our studies it would seem reasonably clear that CGRP is weakly agonistic for the calcitonin receptor on the osteoclast to produce effects on bone resorption and plasma calcium, it is still unclear whether the elevation of bone cyclic AMP simply represents an osteoclastic effect or an additional, more important, effect on osteoblasts. It is highly unlikely that CGRP may exert systemic effects on bone. Nevertheless, the peptide may be an important local regulator of bone cell function.

In addition to calcitonin and katacalcin, it is now known that the human calcitonin gene encodes a novel peptide called calcitonin gene related peptide (CGRP). In experimental animals, CGRP produces vasodilatation and complex changes in plasma calcium. We have now assessed its biological activity in man by infusing human CGRP (hCGRP) into six normal volunteers. hCGRP (545 pmol/min) caused the diastolic pressure to fall from 64 +/- 5 to 55 +/- 7 mmHg (P less than 0.05), the heart rate to increase from 61 +/- 7 to 87 +/- 5 beats/min (P less than 0.05) and the skin temperature to increase from 33.7 +/- 0.9 to 34.9 +/- 0.5 degrees C. Plasma noradrenaline increased from 481 +/- 126 to 835 +/- 65 pg/ml (P less than 0.05) and plasma adrenaline from 57 +/- 17 to 82 +/- 12 pg/ml (P less than 0.05). There were no significant changes in the albumin-corrected plasma calcium. hCGRP is thus a potent endogenous vasodilator in man and is in fact more potent than any other known vasodilator. Together with the observations that CGRP circulates in normal subjects at relatively high concentration (approximately 25 pmol/l) and that CGRP is present in perivascular nerves, this study suggests a possible role for CGRP in controlling peripheral vascular tone in man.