Treatment of malignant hypercalcaemia with clodronate

We have assessed the effects of clodronate (dichloromethylene diphosphonate; Cl2MDP 0.8-3.2g daily by mouth for up to 3 months) in 17 episodes of hypercalcaemia and osteolysis due to carcinoma. Clodronate reduced serum calcium in 14 episodes and bone resorption in all patients. These remained suppressed for the duration of treatment, but recurred promptly when treatment was stopped. Clodronate may be a useful measure for controlling hypercalcaemia and osteolysis in patients with carcinoma.     

Hepatic iron stores and plasma ferritin concentration in patients with sickle cell anemia and thalassemia major

To examine the relationship between hepatic iron stores and plasma ferritin concentration in individuals treated with red cell transfusion and iron chelation therapy, 37 patients with sickle cell anemia and 74 patients with thalassemia major were studied. In each patient, hepatic iron stores were measured by an independently validated noninvasive magnetic method, and plasma ferritin was determined by immunoassay. The correlation between hepatic iron and plasma ferritin was significant both in patients with sickle cell anemia (R = 0.75, P < 0.0001) and in those with thalassemia major (R = 0.76, P < 0.0001). Regression analysis showed no significant difference between the two groups in the linear relationships between hepatic iron stores and plasma ferritin. Considering all 111 transfused patients as a group, the coefficient of correlation between hepatic iron stores and plasma ferritin was highly significant (R = 0.76, P < 0.0001). Regression analysis found that variation in body iron stores, as assessed by magnetic determinations of hepatic iron, accounted for only ～57% of the variation in plasma ferritin, suggesting that the remainder was the result of other factors, such as hemolysis, ineffective erythropoiesis, ascorbate deficiency, inflammation, and liver disease. The 95% prediction intervals for hepatic iron concentration, given the plasma ferritin, were so broad as to make a single determination of plasma ferritin an unreliable predictor of body iron stores. Variability resulting from factors other than iron status limits the clinical usefulness of the plasma ferritin concentration as a predictor of body iron stores. © 1993 Wiley-Liss, Inc.     

An abstinence syndrome following chronic administration of delta-9-tetrahydrocannabinol in rhesus monkeys

Chaired, chronically catheterized rhesus monkeys were administered IV delta-9-tetrahydrocannabinol (THC), 0.5 mg/kg every 6 h for 3 weeks. Following the first THC injection, the animals appeared heavy-lidded, immobile, and unresponsive to observation. Tolerance developed to these behaviors during the 3 weeks of THC administration, although the animals remained subdued compared to baseline. Following discontinuation of THC, animals showed an increase in gross movement, eye contact, and tooth baring of greater frequency and/or duration than observed before THC. This presumably represents a cannabis abstinence syndrome.     

Effects of Normal and Activated Cell Fractions on the Growth of Tubercle Bacilli

Fractions prepared from normal and activated liver cells were tested for the antimycobacterial activity by the agar plate diffusion test. Results showed that lysosome extracts of normal and activated cells exerted no antibacterial activity, cell extracts and lysosome membranes exerted some activity, and cell membranes exerted the strongest activity. The active materials of activated cells exerted stronger antituberculous activity than the corresponding materials of normal cells. Degrees of the antimycobacterial activity of various cell fractions showed a close correlation with the amounts of nonesterified fatty acids. This correlation, as well as other data, suggested that the antimycobacterial activity of cell fractions was caused by toxic fatty acids which were produced during the hydrolysis of lipoporteins or phospholipids by the activity of tissue lipases. The relationship of these findings to the mechanism of cellular immunity is discussed.     

Mechanism of malignant hypercalcaemia in carcinoma of the breast

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.     

Ambulatory monitoring of bladder and detrusor pressure during natural filling

We have developed a system to perform fully ambulatory monitoring studies of the bladder. Bladder and rectal pressures are recorded during natural filling of the bladder for up to 6 hours. This system has been evaluated in 19 studies performed on 15 patients. The mean duration of the studies was 3 hours 51 minutes (standard deviation +/- 1 hour 3 minutes) and the mean number of voids per patient was 3.8 +/- 2.2. Visual inspection of the recorded data showed that subtraction of the rectal trace from the bladder trace provided a useful detrusor trace when subjects were ambulant as well as resting. When ambulant, movement caused typical peak-to-peak pressure variability in the bladder and rectal traces of approximately 30 +/- 20 cm. water (mean and standard deviation of peak-to-peak pressure for typical ambulant 5-minute sections for each patient), which after subtraction was reduced on the detrusor trace to 10 +/- 5 cm. water. The equivalent figures when resting were 9 +/- 5 cm. water, subtracting to less than 5 cm. water for the detrusor. Further measurements also were calculated for the whole of each trace. The system provided good quality recordings and should prove useful in future evaluations of natural fill urodynamic studies.