Effect of 1-deamino-5-D-arginine vasopressin (DDAVP) on plasma cortisol (hydrocortisone).

The influence of 1-deamino-8-D-arginine vasopressin (DDAVP), the new antidiutetic polypeptide without any side effects on plasma cortisol, was investigated in 30 healthy persons. A dose of 4 mug DDAVP administered intravenously induced a rise in plasma cortisol (hydrocortisone) levels greater than 3.5 mug/100 ml in 12 out of 20 persons studied. In this group (group I), the average increase at 15 minutes was 6.92+/-1.74 mug/100 ml (P less than 0.005), while in the remaining eight persons (group II) plasma cortisol levels decreased according to the usual normal daily rhythm. DDAVP, 80 mug, administered intranasally had no demonstrable influence on physiologic plasma cortisol regulation. On the basis of the present findings with relatively low doses, pituitary responsiveness (ACTH release) might be expected to occur in a higher percentage of persons after giving high intravenous doses of DDAVP. Further efforts are necessary to develop a safe vasopressin test for clinical examination of adenohypophyseal function.

Gamma-chain heavy-chain disease with primary thyroid plasmacytoma.

A case of gamma-chain heavy-chain disease was associated with primary thyroid plasmacytoma. The patient has been free of complaints for two years since the removal of the tumorous thyroid. The heavy-chain fragment (molecular weight, 32,000 daltons) has disappeared from the serum and urine, while the previously low levels of normal immunoglobulins have increased. The immunoglobulin anomaly may be correlated with the chronic antigen stimulus.

Cetuximab, gemcitabine and capecitabine in patients with inoperable biliary tract cancer: a phase 2 study.

PURPOSE: Biliary tract cancer is rare and has dismal prognosis. Chemotherapy has its role in inoperable disease but the role of targeted agents like cetuximab remains to be defined. On the basis of high epidermal growth factor receptor expression of biliary tract cancers this study aims to investigate the efficacy of cetuximab, gemcitabine and capecitabine in an exploratory phase 2 trial. PATIENTS AND METHODS: Inoperable biliary tract cancer patients were treated with the combination of gemcitabine (1000 mg/m(2) on day 1 and 8), capecitabine (1300 mg/m(2)/d on day 1-14) and weekly cetuximab (400mg/m(2) loading and 250 mg/m(2) maintenance dose) in 21-d cycles until progression or the appearance of intolerable side-effects. RESULTS: Out of 34 patients (mean age 59.7 years) accrued in this study 16 had intrahepatic, eight extrahepatic cholangiocarcinoma and 10 gall bladder cancer. The best overall response rate was 17.6% (two complete responses and four partial responses) and the clinical benefit rate was 76.5%. After a median of 15.4 months follow-up the median progression free survival was 34.3 weeks and the median overall survival was 62.8 weeks. The performance status and chemotherapy efficacy were independent and significant markers of survival. Only moderate side-effects were registered in this study. KRAS mutation was evaluable in 24 tumours, all of these were of wild type. CONCLUSION: The efficacy of cetuximab, gemcitabine and capecitabine combination is encouraging and a well tolerated treatment of inoperable biliary tract cancers.

Opposite effects of spironolactone and amiloride on potassium excretion in a patient with ascites due to liver cirrhosis.

Potassium excretion was enhanced by spironolactone and it was inhibited by amiloride in a patient with ascites. One drug's effect was counteracted by the other when they were used in combination. Individual variation in the sites of action of antikaluretic drugs might be a possible explanation for the unpredictable changes in potassium excretion induced by these agents.

Effect of toremifene in breast cancer patients. Preliminary communication.

Toremifene, an antiestrogenic drug administered at three dose levels (60, 120, and 300 mg/day) was investigated in 17 postmenopausal patients with advanced breast cancer previously treated with hormonal and/or cytostatic therapy. The drug proved to be well tolerated at all dose levels without any serious side effects even on prolonged administration. Neither response nor side effects have shown any dose dependency in this small group of patients.

Reversal of the suppressed potassium excretion during treatment with combinations of antikaliuretic drugs (spironolactone, canrenone, triamterene, amiloride) in patients with liver cirrhosis.

"Refractory" ascites was drained off by combinations of antialdosterone (spironolactone, canrenone) and pseudoantialdosterone (triamterene, amiloride) drugs inducing as high sodium excretion as 100 mEq per day in two patients with liver cirrhosis kept on a 9 mEq Na diet. Potentiation of the natriuretic effects of the two types of antikaliuretic drugs occurred by real synergism rather than addition. Although natriuretic acitivity showed a typical dose-related pattern, potassium excretion was unpredictable. Significant increase in potassium excretion (reversal of the suppression) occurred when 300 mg triamterene was combined with 200 mg canrenone in one of the two patients and when the dose of spironolactone or canrenone was increased from 200 mg to 600 mg within the combinations with 300 mg triamterene or 20 mg amiloride in the other. Parallel increase in sodium and potassium excretions might be caused by a proximal tubular effect or by inhibition of potassium reabsorption along with sodium in Henle's loop. The vasopressin (DDAVP) refractory distorsion of the relationship between osmolal clearance and free water reabsorpton (induced by pseudo-antialdosterone agents and potentiated by antialdosterone drugs) observed in all the 6 cases of the present patient material favoured the "loop hypothesis".

Dose-response relations in drug-induced inappropriate secretion of ADH: effects of clofibrate and carbamazepine.

The effect of different doses of clofibrate and carbamazepine on water metabolism was compared in a patient with psychogenic polydipsia. A definite relationship was found between the doses of both drugs and the antidiuretic effect. Daily 2--4 g clofibrate was ineffective, but 6--8 g induced the syndrome of inappropriate secretion of ADH. 600 mg carbamazepine a day induced a marked antidiuretic response which could be further augmented by administering daily 1200--1800 mg. The discrepancy between the effective "hypolipidemic" and "antidiuretic" dose of clofibrate may perhaps explain the lack of reports on water intoxication induced by this agent, despite of its entensive use in clinical practice.

Renal response to graded intravenous hypertonic NaCl infusion in healthy and hypertensive subjects:dose-related impairment in distal NaCl reabsorption.

The effects of graded acute intravenous hypertonic NaCl loads on the baseline relationship between osmolal clearance and free water reabsorption established during high NaCl dietary intake and on the fractional excretion of various ions were investigated in 15 healthy subjects and in 12 "normal renin" essential hypertensive patients. No significant influence on the baseline relationship could be demonstrated after a moderate NaCl load in the healthy subjects, while free water reabsorption was depressed by the same intervention in the hypertensive patients. High NaCl loads induced depression of free water reabsorption in a dose-related fashion in both groups. No difference was found in phosphaturia between the groups after the same NaCl load as well as in the healthy persons after different NaCl loads, supporting the contention that the observed differences in free water reabsorption were not due to changes in the proximal neprhon. It was concluded that: (1) impaired NaCl reabsorption in Henle's loop (depression of free water reabsorption) may also occur in response to acute NaCl loadings in healthy subjects, and (2) "exaggerated natriuresis" is the consequence of a normal renal response (impaired NaCl transport in Henle's loop) to a certain degree of volume expansion reset abnormally to a lower level in hypertensive patients.

Pain killing with calcitonin in patients with malignant tumours.

The most essential role of Miacalcic (Calcitonin Sandoz), a 32-amino-acids peptide, is the preservation of osseal integrity. Based on this physiological fact it is assumed that this hormone may have a bone-regenerating effect in bone metastasis formation and sometimes in other malignancies. Though no considerable calcium incorporation could be revealed in our 58 patient treated with Miacalcic, a marked relief of pain was observed in 65.5% of the patients. For objectivation of the subjective pain sensation, the decrease in the quantity of other analgetics used daily, duration of pain and changes of its intensity were studied. These figures were 35.4% on the average, from 12.5-6 h and 23.6%, respectively. The pain-killing character of Miacalcic cannot be explained, but the following assumptions are made: (1) it partially inhibits the synthesis of algogenous peptides; (2) with its possibly cytostatic effect it inhibits the cell proliferation in loco and normalizes the internal pressure of the destroyed region, and (3) by conversion into beta-endorphin it exerts its effect centrally. Compared to the pain-killing effect, the simultaneous improvement of the quality of life seems to be even more essential. It has been proved earlier that a hormone physiologically present, when applied in a high dose, has an analgetic effect, i.e. by utilizing the endogenous substance of the organism, relief of pain can be achieved. We should like to point out that Miacalcic is the only analgetic agent capable of ensuring relief of pain with a simultaneous improvement of the quality of life. Accordingly, the application of Miacalcic in patients suffering from malignant tumours is highly recommended.

Activity of epirubicin in combination chemotherapy of advanced ovarian cancer. Results of the South-East European Oncology Group (SEEOG) Study.

The therapeutic efficacy of the combination of cyclophosphamide + epirubicin + cisplatin was evaluated in 107 previously treated or untreated patients with advanced ovarian cancer. The overall response rate was 58.8%, complete remission 36.4% (mean duration-7.62 months) and partial remission 22.4% (mean duration-6.74 months). The response was rated in function of age, menopausal status, performance status and previous therapy. Toxicity (in case of 109 patients) was evaluated according to the WHO recommendation. The similar therapeutic effectiveness and less toxicity of the above drug combination compared to CAP regimen is demonstrated.

Activity of epirubicin and dibromodulcitol in advanced breast cancer. Results of the South-East European Oncology Group Study.

The therapeutic efficacy of the combination of epirubicin + dibromodulcitol was evaluated in 108 previously treated or untreated patients with advanced breast cancer. The overall response rate was 39.8%, complete remission 3.7% (mean duration 6.3 months) and partial remission 36.1% (mean duration 3.5 months). The response was rated in function of age, menopausal status, performance status and previous therapy. Toxicity (in case of 115 patients) was evaluated according to the WHO recommendation. The similar therapeutic effectiveness and less toxicity of the above drug combination compared to ADM + DBD regimen are demonstrated.