The education and training of personnel auxiliary to dentistry.
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Biomedical subjects
Publications and source records attributed to J Galloway.
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Deflazacort and prednisone were given to 26 patients with rheumatoid arthritis, polymyalgia rheumatica, or other chronic inflammatory diseases, in a double-blind study. Deflazacort rapidly and effectively suppressed disease activity in a manner supporting its assumed therapeutic potency of 83% that of prednisone. Prednisone induced a rapid increase in the level of daily calcium excretion that was not evident with deflazacort. Cortisol secretion was acutely inhibited by prednisone, but not by deflazacort. Neither corticosteroid had a significant effect on glucose metabolism, at the doses studied. Treatment with deflazacort may be an effective alternative to prednisone treatment, with fewer adverse effects on levels of calcium and cortisol, in patients with severe inflammatory conditions warranting the use of glucocorticoids.
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We studied the effect of high doses of biosynthetic human C-peptide on pancreatic hormone secretion in response to oral (75 g) and intravenous [( IV] 0.33 g/kg of D50%) glucose on normal volunteers. The infusion of human C-peptide at a rate of 360 ng/kg/min body weight, increased the plasma C-peptide concentration from a basal level of 0.32 +/- 0.04 pmol/mL to 38.5 +/- 1.8 pmol/ml. Overall, C-peptide had no significant effect on the serum levels of glucose, insulin, proinsulin, glucagon, and pancreatic polypeptide, either under basal conditions or following IV and oral glucose administration. However, small decreases in glucose and insulin concentrations that were not statistically significant were seen during the first hour after C-peptide infusion. The results of the present studies are therefore consistent with the conclusion that even supraphysiologic plasma concentrations of infused C-peptide do not affect basal insulin secretion or overall insulin secretory responses to oral or IV glucose. However, we cannot definitively exclude a small reduction in insulin secretion in the first hour after oral glucose ingestion.
Cardiovascular disease is a frequent cause of morbidity and mortality following renal transplantation. The percentage of deaths due to ischemic cardiovascular disease and cerebrovascular accidents nearly equals that caused by infection among patients receiving their first transplant, according to data from the European Dialysis and Transplant Association Registry. Hypercholesterolemia is a risk factor for cardiovascular disease frequently identified following renal transplantation, and diets low in fat and cholesterol have been suggested as treatment. Previous studies have not reported the response of LDL cholesterol to dietary treatment, and it is this form of cholesterol that is most closely related to cardiovascular disease. The American Heart Association has provided nutritionists with guidelines for the treatment of hyperlipidemic patients which include the Step One Diet. Previous dietary studies of renal transplant recipients have allowed a slightly higher intake of fat than that currently recommended by the AHA. We wondered if an easily reproducible diet well known to nutritionists such as the AHA Step One Diet would be effective in lowering cholesterol levels in hyperlipidemic renal transplant recipients. The purpose of our study was not to define the mechanisms of posttransplant hyperlipidemia, but rather to assess the effectiveness of dietary intervention on hyperlipidemia following renal transplantation.
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1. The effects of three intravenous diphosphonates (etidronate, clodronate and aminohexane diphosphonate) on phosphate homoeostasis were studied in 30 patients with Paget's disease of bone and in three patients with hypoparathyroidism. 2. In Paget's disease, all three diphosphonates induced significant increases in serum phosphate and renal tubular reabsorption of phosphate. This effect was most marked and persistent after etidronate, whereas in the clodronate- and aminohexane diphosphonate-treated patients the increases were less, of shorter duration and followed thereafter by significant decreases in serum phosphate and renal tubular reabsorption of phosphate. Unlike etidronate, both clodronate and aminohexane diphosphonate caused a significant reduction in serum and urinary calcium, with appropriate homoeostatic increases in immunoassayable parathyroid hormone. 3. Phosphaturic responses to infused parathyroid hormone were observed in two patients with etidronate-induced hyperphosphataemia. 4. In three hypoparathyroid patients, clodronate induced a more marked increase in serum phosphate and renal tubular reabsorption of phosphate than in Paget's disease, which was of comparable degree but of shorter duration than that after etidronate in Paget's disease. 5. These findings suggest that all three diphosphonates increase renal tubular reabsorption of phosphate, but that this effect is attenuated with those diphosphonates which induce secondary hyperparathyroidism.
We have assessed the early effects of three diphosphonates on calcium and skeletal homeostasis in 68 patients with Paget's disease of bone treated with daily intravenous infusions for five consecutive days. Both clodronate (300 mg/day) and aminohexane diphosphonate (AHDP; 50 mg/day) induced a fall in serum and urine calcium, and secondary hyperparathyroidism. In contrast, these changes were not observed with etidronate (300-700 mg/day) despite similar effects on bone resorption, as judged by urinary excretion of hydroxyproline with each of the three disphosphonates. Histological studies during the early phase of treatment indicated that etidronate, but not clodronate or AHDP, acutely impaired the accretion of calcium into bone, thereby offsetting a hypocalcaemic response. All three diphosphonates induced significant increases in plasma phosphate and tubular reabsorption of phosphate (TmP/GFR). The increase induced by etidronate remained significantly higher than pretreatment values for one month, whereas those induced by clodronate and AHDP were less marked and ill-sustained, and followed by significant decreases in both measurements. These data indicate that the effects of different diphosphonates on serum calcium homeostasis are heterogeneous, depending not only on the prevailing rate of bone resorption, but also on the rate of bone formation, and the effect of each diphosphonate on bone and mineral accretion.
The skeletal manifestations of hyperparathyroidism are due to the stimulation of osteoclast-mediated bone resorption by high circulating concentrations of parathyroid hormone (PTH). Since diphosphonates inhibit PTH-mediated bone resorption, we assessed the effects of clodronate in 42 patients with hypercalcaemia and increased bone resorption due to primary hyperparathyroidism (20 patients), secondary hyperparathyroidism in chronic renal failure (12 patients on haemodialysis replacement therapy) and tertiary hyperparathyroidism following successful renal transplantation (10 patients). Clodronate (0.8-1.6 g daily by mouth or 300 mg given as an intravenous infusion following five consecutive dialysis treatments) significantly decreased serum calcium and biochemical indices of bone resorption in the three groups studied. In primary and tertiary hyperparathyroidism, serum calcium values remained above the upper limit of the reference range despite suppression of bone resorption due to the unopposed effect of PTH on renal tubular reabsorption of calcium. Prolonged treatment (3 months) was associated with a partial recurrence of hypercalcaemia in 8 of 12 patients with primary hyperparathyroidism despite continued effects on bone resorption, possibly due to a secondary decrease in bone formation. These studies indicate that clodronate is capable of suppressing PTH-mediated bone resorption in disorders of parathyroid secretion and may prove to be a useful adjunct in their medical management.
We undertook this study to examine the accuracy of plasma C-peptide as a marker of insulin secretion. The peripheral kinetics of biosynthetic human C-peptide (BHCP) were studied in 10 normal volunteers and 7 insulin-dependent diabetic patients. Each subject received intravenous bolus injections of BHCP as well as constant and variable rate infusions. After intravenous bolus injections the metabolic clearance rate of BHCP (3.8 +/- 0.1 ml/kg per min, mean +/- SEM) was not significantly different from the value obtained during its constant intravenous infusion (3.9 +/- 0.1 ml/kg per min). The metabolic clearance rate of C-peptide measured during steady state intravenous infusions was constant over a wide concentration range. During experiments in which BHCP was infused at a variable rate, the peripheral concentration of C-peptide did not change in proportion to the infusion rate. Thus, the infusion rate of BHCP could not be calculated accurately as the product of the C-peptide concentration and metabolic clearance rate. However, the non-steady infusion rate of BHCP could be accurately calculated from peripheral C-peptide concentrations using a two-compartment mathematical model when model parameters were derived from the C-peptide decay curve in each subject. Application of this model to predict constant infusions of C-peptide from peripheral C-peptide concentrations resulted in model generated estimates of the C-peptide infusion rate that were 101.5 +/- 3.4% and 100.4 +/- 2.8% of low and high dose rates, respectively. Estimates of the total quantity of C-peptide infused at a variable rate over 240 min based on the two-compartment model represented 104.6 +/- 2.4% of the amount actually infused. Application of this approach to clinical studies will allow the secretion rate of insulin to be estimated with considerable accuracy. The insulin secretion rate in normal subjects after an overnight fast was 89.1 pmol/min, which corresponds with a basal 24-h secretion of 18.6 U.
With the recent availability of biosynthetic human proinsulin there has been a renewed interest in evaluating its metabolic effects, either alone or in combination with insulin. It has been suggested that pretreatment with proinsulin enhances the hypoglycemic response to subsequently administered insulin. On the other hand, the simultaneous administration of proinsulin and insulin has additive, not synergistic, effects. To clarify this question we used the euglycemic glucose clamp technique in 10 normal subjects to compare the steady state effects on glucose disposal of combined infusions of insulin (0.54 microgram/M2 . min, equivalent to 15 mU/M2 . min) and proinsulin (2.75 micrograms/M2 . min) given both simultaneously and sequentially. The mean +/- SEM steady state glucose disposal rates were similar whether the two hormones were given simultaneously (7.2 +/- 0.7 mg/min . kg), after proinsulin pretreatment (7.7 +/- 0.7 mg/min . kg), or after insulin pretreatment (7.1 +/- 0.7 mg/min . kg). The serum proinsulin concentration of 5.39 +/- 0.3 pmol/ml during the infusion of proinsulin alone was unchanged by the simultaneous infusion of insulin, suggesting that in the doses used, insulin did not affect proinsulin clearance. We conclude that in normal subjects there is no enhancement of the combined action of insulin and proinsulin to stimulate glucose disposal by pretreatment with proinsulin or insulin.
To investigate the mechanisms of hypercalcaemia in carcinoma of the breast, 22 patients with hypercalcaemia due to metastatic carcinoma were studied and the findings compared with those obtained in normal subjects and patients with benign and malignant breast disease without hypercalcaemia. As expected, patients with metastases of bone showed biochemical evidence of increased bone resorption. Whereas all patients with hypercalcaemia had skeletal metastases, not all patients with skeletal metastases had hypercalcaemia despite considerable degrees of bone resorption. The presence of hypercalcaemia was associated with a significant increase in renal tubular reabsorption of calcium (p less than 0.001) and decreased reabsorption of phosphate (p less than 0.001) despite adequate rehydration of patients. These studies suggest that increased renal tubular reabsorption of calcium, possibly mediated by a humoral factor with activity similar to that of parathyroid hormone, contributes appreciably to the hypercalcaemia of malignant breast disease.