Cold crucible levitation melting of biomedical Ti-30 wt%Ta alloy.

Recently, titanium-tantalum alloys have been studied as implant materials for dental and orthopedic surgery. However, titanium and tantalum are difficult to mix by common arc melting and induction melting, because of their high melting point and the marked difference between their densities (Ti: 1,680 degrees C, 4.5 g/cm3, Ta: 2,990 degrees C, 16.6 g/cm3). Thus, the Cold Crucible Levitation Melting (CCLM) method was chosen to produce a Ti-30 wt%Ta binary alloy in the present study. The CCLM furnace, with 1 kg capacity, consisted of a water-cooled crucible comprising oxygen-free high purity copper segments and coils wrapped around the crucible and connected to a frequency inverter power supply. A qualified ingot of 1.0 kg of Ti-30 wt%Ta alloy was obtained. The ingot was characterized from the surface quality, chemical composition distribution and microstructure, and finally the melting process was discussed.

Pamidronate treatment in patients with tumor-associated hypercalcemia: pharmacological effects and pharmacokinetics.

The purpose of this study was to investigate the effects of pamidronate, a second generation bisphosphonate, on the change in calcium homeostasis in patients with tumor-associated hypercalcemia. Eight patients with tumor-associated hypercalcemia received intravenous infusion of pamidronate (45 mg) and their high mean serum calcium concentration significantly decreased from 3.56 mmol/L to 2.62 mmol/L7 days after treatment. Serum intact PTH before treatment had been suppressed to below normal in all patients but returned to normal range in six patients within 7 days after treatment. Urinary PTH related peptide (PTHrP) excretion before treatment had been elevated in seven patients and then significantly increased further after pamidronate therapy. The serum bone Gla protein concentration was not apparently changed by the treatment. Pamidronate in serum was rapidly eliminated after the treatment and urinary excretion reached a plateau on the second day (13.8% of the administered dose), suggesting that the major portion of the infused dose had been distributed to the bone and other tissues. These findings suggest that pamidronate has a potent hypocalcemic effect and that PTHrP production in malignant tumors could be affected by pamidronate therapy.

Effect of metyrapone pretreatment on adrenocorticotropin secretion induced by corticotropin-releasing hormone in normal subjects and patients with Cushing's disease.

To examine the influence of endogenous cortisol on the ACTH response to CRH, we compared ACTH secretion during CRH tests before and after metyrapone administration in 9 normal subjects and 12 patients with Cushing's disease. The administration of 4.5 g metyrapone (750 mg, orally, every 4 h) resulted in a decrease in basal (pre-CRH) plasma cortisol levels and an increase in basal plasma ACTH levels in both normal subjects and Cushing's patients. The pretreatment with metyrapone significantly blunted the increase in plasma cortisol levels and markedly enhanced ACTH secretion after iv injection of 100 micrograms human CRH. The peak ACTH levels during CRH test before and after metyrapone administration were 8 +/- 1 and 58 +/- 8 pmol/L, respectively, in normal subjects (P less than 0.01) and 26 +/- 5 and 50 +/- 11 pmol/L, respectively, in Cushing's patients (P less than 0.05). Although the basal and peak ACTH levels as well as delta ACTH (peak ACTH - basal ACTH) during the CRH test before metyrapone administration were significantly higher in Cushing's disease patients than in normal subjects (P less than 0.01), no such difference was observed between the 2 groups after metyrapone administration. The results clearly indicate that the endogenous cortisol levels greatly influence the ACTH response to CRH, and that the CRH test as commonly performed does not allow a correct evaluation of potential responsiveness of normal pituitaries and Cushing's adenomas to CRH.

Neurohypophyseal function in postpartum hypopituitarism: impaired plasma vasopressin response to osmotic stimuli.

We studied neurohypophyseal function in 12 women with postpartum hypopituitarism (Sheehan's syndrome) by measuring plasma arginine vasopressin concentrations during 5% hypertonic saline infusions. All patients had a history of obstetric shock or massive bleeding, and were receiving cortisol and/or L-T4 replacement therapy. None had any symptoms of diabetes insipidus. The mean basal plasma vasopressin level in the patients [0.6 +/- 0.1 (+/- SE) pmol/L] was significantly lower (P less than 0.01) than that in normal adults (2.5 +/- 0.5 pmol/L; n = 12), whereas mean plasma osmolality values were similar in the two groups. During hypertonic saline infusion, the 10 hypopituitary patients had varying degrees of subnormal arginine vasopressin responses to the increase in plasma osmolality. Urine-concentrating ability after dehydration also was lower in the patients, although overt polyuria was absent at the time of this study. These results indicate that the osmoregulation of arginine vasopressin secretion is frequently impaired in postpartum hypopituitarism, suggesting neurohypophyseal damage.

High activity of cyclic 3',5'-nucleotide phosphodiesterase in sera of patient with phaeochromocytoma.

Our previous observations that serum cyclic 3',5'-nucleotide phosphodiesterase activity varied in thyroid disorders and was positively correlated with thyroid function stimulated us to investigate the phosphodiesterase levels in sera of patients with pituitary and adrenal disorders, and the response to glucagon in normal subjects. Both serum cyclic AMP phosphodiesterase (cyclic AMP-PDE) and cyclic GMP phosphodiesterase (cyclic GMP-PDE) activities were measured at a low substrate concentration. Serum cyclic AMP-PDE activity was elevated in five patients with phaeochromocytoma and was not elevated in patients with Cushing's syndrome or acromegaly, compared to the level in normal subjects. Increased enzyme activities returned to normal after resection of the tumours. Intramuscular injection of glucagon to five healthy subjects elevated cyclic AMP levels and cyclic AMP-PDE activity in plasma. These results imply that the increased cyclic AMP level by the activation of cyclase may have induced cyclic AMP-PDE in the target organ and the soluble cyclic AMP-PDE may leak into blood vessels from target organs.

Effect of fusaric acid (a dopamine beta-hydroxylase inhibitor) on phaeochromocytoma.

Fusaric acid, an inhibitor of dopamine beta-hydroxylase, which converts dopamine to noradrenaline, lowered the blood pressure and induced a subjective improvement in patients with phaeochromocytoma. These effects may be due either to an impairment of catecholamine biosynthesis or to a direct action on the blood vessels. The use of this drug in the treatment of patients with inoperable malignant phaeochromocytoma or neuroblastoma may improve symptoms and prolong survival.

Serum cyclic 3',5'-nucleotide phosphodiesterase in patients with various thyroid disorders.

Previous observations that cyclic 3',5'-nucleotide phosphodiesterase activity exists in mammalian sera including human serum prompted us to investigate the phosphodiesterase levels in sera of patients with various thyroid disorders. Both serum cyclic AMP phosphodiesterase (cAMP-PDE) and cyclic GMP phosphodiesterase (cGMP-PDE) activities measured in a low substrate concentration were elevated 3-fold in subacute thyroiditis and slightly in hyperthyroidism, compared to the normal. Slight decreases of these enzyme activities were observed in primary hypothyroidism. PDE activities were positively correlated with the value of T3-RSU and serum thyroid hormone levels in hyper- and hypothyroidism. Altered enzyme activities returned to normal during the course of recovery. Identical results were obtained when plasma was tested. These results suggest that serum PDE activities may be partly related to the thyroid function.

[Serum cortisol fractions in breast cancer].

Serum cortisol fractions were determined by isocolloidosmolar equilibrium dialysis in 93 women with breast cancer and 29 normal women. In breast cancer patients, the percentage of protein-unbound cortisol was increased at any concentration of total serum cortisol; this was accompanied by a relative decrease in the percentage of transcortin-bound cortisol. A significant increase in the unbound fraction is indicative of accelerated physiological activity of cortisol in breast cancer patients. In the breast cancer cases, there was a high incidence of obesity (61%) and impaired glucose tolerance (85%). In obese and/or diabetic patients, more remarkable increases of unbound cortisol were observed. We suggest that obesity and impaired glucose tolerance may increase the risk for breast cancer, and that the characteristic increase in the unbound cortisol fraction in women with breast cancer may reflect such risk factors.