SUMMARY To evaluate the physiological effects of human atrial natriuretic factor-(99-126) (ANF), we infused ANF, 0.1, 0.3, and 1.0 /ig/min, or placebo for 125 minutes on different days into six sodium-deprived normal men. During the last 45 minutes of infusion, angiotensin II, 6 ng/kg/min, was infused. Blood pressure, heart rate, plasma concentrations of ANF, aldosterone, and cortisol, and plasma renin activity (PRA) were measured before and during infusion. Steady state mean plasma ANF levels during infusion were 26.2 (placebo), 68.8 (0.1 n% ANF/min), 221 (0.3 ng ANF/min), and 648 pg/ml (1.0 /ig ANF/min). Systolic blood pressure fell significantly (with 1.0 /xg ANF/min), and diastolk pressure tended to rise in a dose-dependent manner, while heart rate was unchanged. PRA and plasma aldosterone fell during ANF infusion in a dose-dependent manner (significant with 0. A TRIAL natriuretic factor (ANF) may be phys-Z.\ iologically and pathophysiologically in-J-\~ volved in ridding the body of a sodium load and in preventing central venous pressure from rising above a certain limit.1 Most of the ANF activity in human plasma seems to be due to human However, it is controversial whether the effect of ANF on aldosterone secretion occurs with near-normal plasma concentrations of the cardiac peptide and whether the effect in vivo is more or less mediated by changes in plasma renin levels. 9 -11 In the present study, we attempted to find a threshold dose of infused ANF that significantly affects aldosterone and renin secretion in sodium-deprived normal men. Subjects and Methods Six healthy men (age range, 20-29 years; body weight range, 63-87 kg; mean body weight, 73.5 ± 8.5 kg) consented to participate in the study, the protocol of which had been approved by the ethical committee of Klinikum Steglitz (Berlin, West Germany). They were studied on 4 different days (three doses of ANF, one placebo infusion) within two periods of sodium depletion, during which the men collected their urine for the calculation of sodium and potassium balances. Sodium losses were induced to facilitate studying a possible suppressive effect of ANF on elevated basal renin and aldosterone levels. A period of sodium depletion consisted of 3 days on a low sodium diet (15 mmol sodium, 70 mmol potassium per day) plus a single 40-mg dose of furosemide (Lasix, Hoechst) on the morning of the first day. Therefore, most of the sodium loss occurred during the first 24 hours of the sodium depletion period, and the cumulative negative sodium balance at the end of Day 3 was not much different from that on the morning of Day 2. Infusion of one dose of ANF or placebo was given in the afternoon on Days 2 and 3. After an interval of 3 weeks on a free diet, the procedure of sodium depletion was

A study of immunological markers was performed in 16 patients with newly diagnosed refractory anaemia with excess of blasts (RAEB) and RAEB in transformation (RAEB-T) and in 12 other patients with acute myeloid leukaemia evolving from RAEB or RAEB-T. Immunocytochemical investigation of bone marrow blasts was done using a modified indirect immunoperoxidase technique. This method permitted accurate morphological identification of blasts and other cells in bone marrow. The monoclonal antibodies used in RAEB and RAEB-T samples were anti-CD34, -c-kit, -HLA-DR and -CD13. The range of CD34 expression of blasts in RAEB samples was 1-14% (mean 6.2%) and in RAEB-T samples 29-48% (mean 35.5%). CD34 positivity was detected in 3-94% (mean 47.4%) of the bone marrow blasts in acute myeloid leukaemia evolving from RAEB and RAEB-T. Expression of c-kit was demonstrated only in a low percentage of blast cells in RAEB, RAEB-T and acute myeloid leukaemia following myelodysplasia. A high percentage (> 30%) of blasts in most patients with RAEB, RAEB-T and acute myeloid leukaemia was HLA-DR and CD13 positive. We observed the transformation from RAEB to acute myeloid leukaemia in three patients. The proportion of CD34 positive blasts increased to 25% and 32% in two patients. The third patient showed an unchanged percentage of CD34 positivity of blasts. These findings indicate that the CD34 positivity of blasts increases with the progression of myelodysplasia to RAEB-T and acute myeloid leukaemia demonstrating the instability of the clonal defect in myelodysplasia.

Summary:Advances in therapy of intermediate-or high-grade nonHodgkin's lymphomas (NHL) and Hodgkin's disease (HD) are one of the most important breakthroughs in oncology. Patients with relapsed or refractory non-Hodgkin's lymphomas (NHL) and Hodgkin's disease (HD) withUsing CHOP or newer second-and third-generation regimens, about 30-50% of patients with advanced NHL will recurrences after an anthracyclin-containing regimen only have a chance of cure of below 10% with convenachieve long-term disease-free survival (DFS). 1,2 Nevertheless, the outcome of the remaining 50-70% of patients who tional chemotherapy. In order to improve their prognosis, we started a phase I/II trial using high-dose therdo not achieve complete remission (CR) or who relapse is dismal. The 2-year disease-free survival with conventional apy comprising carboplatin, together with etoposide and ifosfamide (CEI), followed by autologous stem cell salvage chemotherapy regimens is less than 15% in most studies. [3][4][5] Therefore, several approaches have been made rescue (ASCR) as consolidation after salvage treatment. Since September 1990, 40 patients with intensively preto increase CR and DFS rates, most of them using highdose chemotherapy (HDT) regimens Ϯ total body treated advanced NHL (n = 24) or HD (n = 16) received one cycle of high-dose therapy (HDT) consisting of carirradiation (TBI) with autologous stem cell support. Widely used chemotherapeutic agents have been cyclophosphamboplatin 1500 mg/m 2 , ifosfamide 10 g/m 2 and etoposide in escalating doses from 1200 mg/m 2 to 2400 mg/m 2 folide, cytosine arabinoside, etoposide and BCNU. Combinations of three or four drugs in high dosages have regulowed by ASCR. Thirty-nine patients were assessable for toxicity and response. The following doses appeared larly shown substantial toxicitiy. [6][7][8] One possible way to improve results of HDT is with nonto be safe: carboplatin 1500 mg/m 2 , etoposide 2400 mg/m 2 and ifosfamide 10 g/m 2 . All patients developed crossresistant drugs which were not used during first-line and salvage treatment. They should have low non-hematograde 3 nausea and grade 3 or 4 mucositis. Granulocytopenic fever occurred in 100% with grade 4 infeclogic toxicity even in escalated doses. The topoisomerase II inhibitor etoposide has become one of the most effective tions in 15%. Mild transient kidney toxicity was noted in 36% and liver toxicity in 20% of patients. One toxic drugs for the treatment of NHL. Its synergism with alkylating agents and its limited non-hematologic toxicity makes death occurred (2.5%). Objective responses were obtained in 36 of 39 patients (92%) with complete it useful for combination in HDT. 9,10 Ifosfamide is an oxazaphosphorine alkylating agent with a broad spectrum of remissions (CR) in 24 patients (61.5%) and partial remissions (PR) in 12 (30.7%). Median observation antineoplastic activity producing favorable response rates, for example, in germ cell cancer, ovarian carcinoma, NHL time for surviving patients was 23.3 months (range 3.4-52.3). The ...

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