Two Cases of Malignancy-Associated Hypercalcemia Treated with Mithramycin

The hypocalcemic effect of mithramycin, an antitumor antibiotic,was studied in two consecutive hypercalcemic patients with malignancy.Case 1 was a 60-year-old woman with advanced breast cancer.Severe, generalized bone metastasis seemed to be the cause ofthe hypercalcemia. Serum calcium levels reached 14.6mg/dl (ionizedcalcium 3.84 mEq/I) despite continued therapy with saline (5liters/day) with frosemide (60mg/day, intravenously), high dosesof elcatonin (up to 440 MRC units/day) and prednisolone (30mg/day). Case 2 was a 49-year-old woman with recurrence of ovariancancer. Bone metastasis was not found on X-ray films. Hypercalcemiawas progressive in spite of extensive treatments with saline(2 liters/day) with frosemide (40 mg/day), indomethacin (150mg/day), elcatonin (160 MRC units/day) and prednisolone (30mg/day). Meantime, serum calcium rose to 14.6mg/dl (ionizedcalcium 3.57 mEq/I). In both cases, mithramycin (1.25 mg) wasthen administered intravenously. Serum calcium levels droppedto 9.6 and 9.4 mg/dl two days after the administration of mithramycinin case 1 and case 2, respectively. These observations indicate that mithramycin is more effectivethan any other drug tested for the treatment of hypercalcemiacaused by malignancy irrespective of the presence or absenceof bone metastasis. Therefore, it should be widely used forhypercalcemic emergency.     

Plasmoptysis and Gelation of Erythrocytes in Coagulation of Blood of Freshwater Bony Fishes

1. A clot-like material which results from very rapid plasmoptysis andhydrophyllic swelling of karyoplasm of erythrocytes from freshwater fishwas reported. This attribute was found to a lesser degree in erythrocytes froman amphibian, but it was almost lacking in those of an aquatic reptile.

2. Rapid clotting of fish blood with the usual clinical methods was confirmed in this work. Fish blood clotted more quickly with the slide test thanwith the capillary tube test. In the presence of water, complete coagulationof fish blood occurred in only 65 per cent of the time required for clottingto be completed in air. This speed is attributed to the water-erythrocyte reaction, and not to a quality of the plasma.

3. An attempt was made to correlate the findings with the need forhemostasis and blood coagulation that is peculiar to aquatic vertebrates.

Submitted on September 17, 1958 Accepted on June 28, 1959     

NEUROMUSCULAR EFFECTS OF I.A. INFUSION OF LIGNOCAINE IN MAN

Neuromuscular effects of lignocaine during and after i.a. infusionwere studied in healthy adult patients, using evoked electromyography.Supramaximal, paired stimuli were applied to the ulnar nervewith variable intervals between the two stimuli. The amplitudeof the hypothenar muscle action potential to the second componentof the paired stimulus (test response) was compared with thatevoked by the first component (conditioning response). Duringand after i.a. infusion of lignocaine, there were marked decreasesof the test response at intervals from 7 to 100 ms after theconditioning stimulus, although the decreases of the conditioningresponse were slight or negligible. The finding of decreasedtest responses coincided with the results obtained with tetanicstimulation such as pronounced fade and only slight post-tetanicpotentiation. Differences between these findings and those foundwith muscle relaxants were compared, and it was concluded thatthe mechanism responsible for these results might be attributedto an effect of lignocaine on the motor nerve terminal.     

Definitive Diagnosis of Pancreatic Carcinoma with Percutaneons Fine Needle Aspiration Biopsy Under Ultrasonic Guidance

Definitive diagnosis of pancreatic cancer presents difficulties in that positive identification is often possible only by intraoperative biopsy. Recently, ultrasonic visualization of the pancreas has made preoperative diagnosis possible by furnishing a guide to percutaneous biopsy via a flexible 23-gauge, 0.6 mm. needle.     

A Case of Small Cell Carcinoma of the Lung Producing ADH, ACTH, MSH and Calcitonin: Successful Treatment of Severe Hyponatremia with Furosemide and Hypertonic Saline

A 48-year-old man with a small cell carcinoma of the lung presentedhyponatremia and was diagnosed as having the syndrome of inappropriateADH secretion. A plasma ADH bioassay confirmed this syndrome.During the clinical course, the patient developed a hyponatremiccrisis with a serum sodium of 108mEq/l. His hyponatremia wasrapidly corrected by infusing furosemide in conjunction withhypertonic saline. The postmortem studies demonstrated ADH bioactivityin the tumor tissues, as well as immunoreactive ACTH, ß-MSHand calcitonin. Tumor hypersecretion of ACTH appeared to bethe cause of the patient's hyperresponsiveness to exogenousACTH and of the bilateral adrenocortical hyperplasia observedat the time of autopsy. Therefore, this was a case of a multiple hormone-producing smallcell carcinoma of the lung, in which the severe clinical manifestationsof SIADH were successfully treated with furosemide and hypertonicsaline.     

Tamoxifen in Advanced Breast Cancer; Response Rate, Effect on Pituitary Hormone Reserve and Binding Affinity to Estrogen Receptor

Patients with advanced breast cancer were treated with antiestrogen,tamoxifen, 20 mg orally, twice a day. Of the evaluable 23 patients,one achieved complete response with a duration of 16 months,and five achieved partial response lasting from two to eightmonths, indicating that the response rate was 26%. In the fiveperi-and postmenopausal patients, basal and LH-RH stimulatedplasma LH levels decreased but stayed within the postmenopausalrange in three patients during the tamoxifen therapy. Basaland LH-RH stimulated FSH levels decreased also but stayed withinthe postmenopausal range in all five patients. In a premenopausalpatient, basal and stimulated plasma LH and FSH levels did notchange significantly during the tamoxifen therapy. The plasmaTSH responses did not change significantly. In three of thesix patients, basal and TRH-stimulated prolactin levels decreasedslightly during the tamoxifen therapy. These relatively inconsistentand small changes in the pituitary hormone secretion observedduring the tamoxifen therapy suggest that the anti-tumor effectof tamoxifen was not due to alteration of the pituitary hormonesecretion. The binding of tamoxifen for the estrogen receptorwas examined in the estrogen receptor assay system. The doseresponse curve for tamoxifen was parallel to that for estradiol,indicating that tamoxifen competes with estradiol for the estrogenreceptor. The affinity constants of tamoxifen for the estrogenreceptor in eight cytosols of human breast cancer tissues were(139 ±79) X 10^–10M (mean±SD), indicatingthat the binding affinity of tamoxifen was about 0.7% that ofestradiol. The affinity constants for nuclear receptors weresimilar to those for cytosol receptors. These data suggest thattamoxifen is a useful drug for treatment of advanced breastcancer, and that the anti-tumor effect could be related to itsbinding to estrogen receptors in tumor tissues, and not causedby altering the secretion of pituitary hormones.