SULFISOMIDINE IN THE TREATMENT OF PERTUSSIS

Sulfisomidine and pertussis serum were used in the treatment of 21 patients with pertussis. Twenty of the patients were under six months of age and seven had bronchopneumonia.Therapeutic concentrations of the drug in the blood were obtained in 14 cases when it was given in dosage of 0.26 gm. per kilogram of body weight per 24 hours.The average stay in hospital was ten days. None of the patients died. Hematuria developed in one case but crystalluria was not concomitant and it abated promptly when fluid intake was increased.     

Differential effects of nitrogen mustard in vivo on the cancer and host cells in MCa-11 tumours

We analysed the effects of nitrogen mustard (HN₂) on the growth, cell cycle distributions, and ratios of tumour cells to host cells for MCa-11 tumours grown in vivo. Treatment of tumour-bearing BALB/c mice with 3 mg/kg of HN₂ produced a significant slowing of MCa-11 tumour growth. Seventy-two hours after treatment in vivo with either 3 or 4 mg/kg of HN₂, the host cells in the treated tumours showed a significantly decreased G₀/G₁ peak and an increased G₂/M peak (P < 0.01), whereas the cancer cells in the treated tumours showed significant increases in the G₀/G₁ peak coupled with relatively decreased proportions of S and G₂/M tumour cells (P < 0.001). The ratio of the total number of cancer cells to the total number of host cells in the tumours was significantly increased 72 h after HN₂ administration (P<0.01). Thirty-two days after treatment with HN₂, the cell cycle distributions of the host and tumour cells in the treatment and control tumours had returned to being identical, but the ratio of the total number of cancer cells to the total number of host cells remained increased in the treated tumours (P<0.01). These results show that the administration in vivo of HN₂ can lead to entirely different cell cycle effects for the host and cancer cells in the same tumour, and that the partial growth arrest of MCa-11 tumours from HN₂ treatment may be due in part to the preferential destruction of host cells rather than solely to a direct cytotoxic effect on the cancer cells.     

Validity of VO(2 max) in predicting blood volume: implications for the effect of fitness on aging

A multiple regression model was constructed to investigate the premise that blood volume (BV) could be predicted using several anthropometric variables, age, and maximal oxygen uptake (VO(2 max)). To test this hypothesis, age, calculated body surface area (height/weight composite), percent body fat (hydrostatic weight), and VO(2 max) were regressed on to BV using data obtained from 66 normal healthy men. Results from the evaluation of the full model indicated that the most parsimonious result was obtained when age and VO(2 max) were regressed on BV expressed per kilogram body weight. The full model accounted for 52% of the total variance in BV per kilogram body weight. Both age and VO(2 max) were related to BV in the positive direction. Percent body fat contributed <1% to the explained variance in BV when expressed in absolute BV (ml) or as BV per kilogram body weight. When the model was cross validated on 41 new subjects and BV per kilogram body weight was reexpressed as raw BV, the results indicated that the statistical model would be stable under cross validation (e.g., predictive applications) with an accuracy of +/- 1,200 ml at 95% confidence. Our results support the hypothesis that BV is an increasing function of aerobic fitness and to a lesser extent the age of the subject. The results may have implication as to a mechanism by which aerobic fitness and activity may be protective against reduced BV associated with aging.     

Potentiation of carbon tetrachloride hepatotoxicity by chlordecone: Dose-response relationships and increased covalent binding in vivo

Chlordecone greatly potentiates carbon tetrachloride (CC1₄) hepatotoxicity. In order to quantitate the degree of this potentiation, the effects of a range of doses of CC1₄ on two microsomal enzymatic functions and liver enzyme release were examined in chlordecone-treated and control rats. Male Sprague-Dawley rats were pretreated with 15 mg chlordecone per kilogram body weight (BW) intragastrically or with vehicle. After 48 hours, 0 to 250 μ1 CC1₄ per 100 g body weight were given intraperitoneally (IP), and the rats were killed 24 hours later. Chlordecone treatment produced approximately a 17-fold potentiation of the CC1₄ dependent loss of cytochrome P-450 and glucose-6-phosphatase activity, so that a dose of 6 μ1 CC1₄ per 100 g body weight in the chlordecone-treated animals resulted in a similar amount of damage as observed with 100 μ1 CC1₄ per 100 g body weight in controls. A similar potentiation by chlordecone was seen with CC1₄- induced increases in serum glutamic-oxaloacetic transaminase (SGOT) levels. Chlordecone treatment also increased hepatic cytochrome P-450 levels by 67% and resulted in an increase in the covalent binding of [14-C]-CC1₄-derived metabolites to microsomal protein and lipid in vivo.     

Metabolism of fluoroacetate in the skink (Tiliqua rugosa) and the rat (Rattus norvegicus)

Administration of 100 mg sodium fluoroacetate (compound 1080) per kilogram body weight to T. rugosa resulted in a 3.4-fold increase in plasma citrate levels 48 h after dosing while administration of 3 mg sodium fluoroacetate per kilogram body weight to R. norvegicus produced a fivefold increase in plasma citrate levels within 4 h. Administration of 300 mg sodium fluoroacetate per kilogram body weight reduced the oxygen consumption of the skink by between 2.5 and 11% while in the rat, 2 mg sodium fluoroacetate per kilogram body weight reduced oxygen consumption by between 28 and 57%. Aconitate hydratase activity in extracts of liver acetone powders from T. rugosa was less inhibited by (-)erythrofluorocitrate (Ki: 0.065 mM) than that in extracts derived from R. norvegicus (Ki: 0.026 mM). The rate of defluorination of fluoroacetate in erythrocytes and in extracts of liver acetone powders of T. rugosa was 8- and 4.5-fold greater, respectively, than that found in similar preparations from R. norvegicus. A rapid rate of defluorination together with a low reliance on aerobic respiration favoured detoxification of fluoroacetate in T. rugosa rather than its conversion into fluorocitrate. Though defluorination in this species helped to minimize the immediate effects of fluoroacetate on aerobic respiration, it resulted in rapid depletion of liver glutathione levels.     

Single administration of low dose cyclophosphamide augments the antitumor effect of dendritic cell vaccine

Single administration of low dose cyclophosphamide (CTX) was previously reported to enhance the antitumor efficacy of immunotherapies. To investigate the possible mechanisms for this effect, we examined whether a single administration of low dose CTX could augment the immunogenicity of dendritic cell (DC) vaccines. Fifty milligrams per kilogram body weight dose of CTX was administrated intraperitoneally to mice after B16 melanoma or C26 colon carcinoma tumor models were established, DC vaccine generated from mouse bone marrow and pulsed with B16 or C26 tumor cells lysates were vaccinated 4 days later. CTX treatment potentiated the antitumor effects of the DC vaccine, and increased the proportion of IFN-γ secreting lymphocytes in spleens. Furthermore, a significantly reduced proportion of CD4+CD25+FoxP3+ regulatory T (T_reg) cells was detected by flow cytometry in spleen lymphocytes from tumor-bearing mice treated with CTX. Thus, a single administration of low dose CTX could augment antitumor immune responses of DC vaccine by reducing the proportion of CD4+CD25+FoxP3+ T_reg cells in tumor-bearing mice. Our results suggested a possible mechanism of CTX-induced immunopotentiation and provided a strategy of immunotherapy combining a low dose CTX with DC vaccine. J.-Y. Liu and Y. Wu contributed equally to this work.     

Increases in Phosphorus Requirements for CO(2)-Enriched Pine Species

Pinus radiata D. Don (half-sib families 20010 and 20062) and Pinus caribaea var hondurensis (an open-pollinated family) were grown for 49 weeks at seven levels of phosphorus and at CO₂ concentrations of either 340 or 660 microliters per liter, to establish if the phosphorus requirements differed between the CO₂ concentrations and if mycorrhizal associations were affected. When soil phosphorus availability was low, phosphorus uptake was increased by elevated CO₂. This may have been related to changes in mycorrhizal competition. When the phosphorus concentration in the youngest fully expanded needles was above 600 milligrams per kilogram the shoot weight of all pine families was greater at high CO₂ due to increases in rates of photosynthesis. More dry weight was partitioned to the stems of P. radiata family 20010 and P. caribaea. At foliar phosphorus concentrations above 1000 milligrams per kilogram (P. radiata) and 700 milligrams per kilogram (P. caribaea), growth did not increase at 340 microliters of CO₂ per liter. Soluble sugar levels in the same needles mirrored the growth response, but the starch concentration declined with increasing phosphorus. At 660 microliters of CO₂ per liter, shoot weight and soluble sugar concentrations were still increasing up to a foliar P concentration of 1800 milligrams per kilogram for P. radiata and 1600 milligrams per kilogram for P. caribaea. The starch concentrations did not decline. These results indicate that higher foliar phosphorus concentrations are required to realize the maximum growth potential of pines at elevated CO₂.     

Alterations in platelet aggregation and microsomal benzo-α-pyrene hydroxylase activities after exposure of rats to a prudhoe bay crude oil

Administration of a Prudhoe Bay crude oil (PBCO) to rats has been shown to (a) inhibit platelet aggregation induced by adenosine diphosphate (ADP), arachidonic acid, or epinephrine and (b) induce benzo-α-pyrene hydroxylase (BPH) in the liver and small intestine. Maximum inhibition of aggregation (90%) was seen 12 to 16 hours subsequent to dosing. However, substantial inhibition was observed as early as four hours and as late as 48 hours after dosing. Of particular interest was the sensitivity of the platelet response compared with the putatively sensitive response of monooxygenase induction in liver. As little as 0.1 ml of PBCO per kilogram body weight (bw) caused an inhibition of aggregation with all three agonists. A similar inhibition of the release of ADP from platelets in the presence of arachidonic acid or epinephrine was also observed. In contrast, hepatic BPH activity showed only a modest increase (67%) over the control value even after administration of 2 ml of PBCO per kilogram body weight. Small intestine BPH activity was more sensitive, showing a gradual increase of up to 19-fold 24 hours after dosing with 2 ml of PBCO per kilogram body weight. The sensitivity of the platelet response is of general environmental interest and evaluating platelet aggregation in humans may be important as a noninvasive assay for exposure to either accidental or “acceptable” levels of petroleum hydrocarbons in the occupational environment.     

Blood volume in cardiac decompensation; determinations by use of radiochromium

RADIOCHROMIUM HAS THESE ADVANTAGES FOR THE MEASUREMENT OF WHOLE BLOOD VOLUME: it remains in the erythrocytes many hours; it can be measured easily and accurately; the amount of radiation from it is very low.As measured by the radiochromium method, the whole blood volume of normal patients was determined to be 65.6 cc. +/- 5.95 cc. per kilogram of body weight or 2.49 +/- 0.28 liters per square meter of body surface. In a majority of a series of patients with heart disease, hypervolemia was found during right ventricular failure but not in those having left ventricular failure or mitral stenosis alone.     

Reversibility of the reproductive toxicity of gossypol in peripubertal bulls

Gossypol has been shown to impair sperm production in male ruminants. The purpose of this study was to determine if the adverse effects of gossypol on spermatogenesis in peripubertal bulls were reversible. Twenty-eight crossbred Angus bulls were allocated into treated and control groups at 11 months of age. For 8 weeks, treated bulls were fed a ration containing 8 mg of free gossypol per kilogram of body weight per day while control bulls were fed a soybean meal ration free of gossypol. At 28-days intervals, scrotal circumference was measured and semen collected to assess sperm motility and morphology. Seven control and seven treated animals were castrated 56 days after the start of the experiment and the testes were examined histologically. The remaining bulls were fed a gossypol-free diet for 210 days prior to castration. There were significant increases in primary and secondary sperm abnormalities in treated bulls 28 and 56 days after gossypol feeding. The number of sperm with proximal droplets was significantly higher in gossypol-treated bulls, suggesting testicular degeneration. There was no significant effect on the sperm motility, scrotal circumference, or histopathological characteristics of the testes. Four weeks after the end of gossypol feeding, primary and secondary abnormalities were still increased in gossypol-treated bulls, however in subsequent collection periods the percentage of abnormalities were similar between groups. At 210 days, there was no treatment effect on scrotal circumference, and histological characteristics of the testes were not different between groups. The deleterious effects of gossypol on the morphological characteristics of spermatozoa were reversible. Gossypol (8 mg/kg per day for 56 days) increased sperm abnormalities but the effects were reversible.     

Changes of Endogenous Gibberellin-like Substances with Sex Reversal of the Apical Inflorescence of Corn

In developing apical meristems of corn, the level of acidic, ethyl acetate-soluble gibberellin (GA)-like substances increased to a maximum of 108 micrograms GA₃-equivalents per kilogram dry weight of tissue at inflorescence initiation, and then fell rapidly. At anthesis, only a trace (0.2 microgram per kilogram) of GA-like activity remained in the apical (male) inflorescences, whereas moderate activity (32 micrograms per kilogram), mostly of a nonpolar nature, was present in lateral, female, inflorescences.     

Estimation of lung liquid production in fetal sheep with blue dye dextran and radioiodinated serum albumin.

Lung liquid production and reabsorption rates and lung volumes were measured in 99 fetal sheep (119-148 days of gestation) by indicator-dilution methods with the simultaneous use of blue dye dextran (BDD) and radioiodinated serum albumin (RISA). There were no significant differences between rates of lung liquid production or reabsorption by the two methods (n = 71 pairs; paired t-test; Wilcoxon test; ANOVA); this was equally true for rates in milliliters per hour or milliliters per kilogram body weight per hour and was independent of age. Volumes measured by both methods showed a close linear relationship (r = 0.97; for slope P < 0.0001; n = 99), whether expressed as milliliters or milliliters per kilogram body weight. Either method could give the higher volume. Values differed by only approximately 4%, independent of age or parameter (ml or ml/kg body wt; volumes regressed to original volume, or as measured in untreated control hours). However, this small difference was significant by paired t-test or Wilcoxon test when all data were combined irrespective of age; it was not significant after allowance for gestational age (two-way ANOVA). Both indicators showed the same increase in lung volume toward birth and the same fall when related to body weight (slopes significant P = 0.0003-0.0004; r = 0.93). Two-way ANOVA showed that the declines were significant (P = 0.003). The data suggest that 1) there was no significant difference in production or reabsorption rates measured by BDD or RISA, 2) differences in volumes measured by the two indicators were only significant if gestational age was ignored and were too small to have physiological importance, and 3) although BDD and RISA each may have methodological weaknesses, for purposes of measuring lung liquid volumes both are sufficiently accurate and reproducible to obtain meaningful physiological results.     

Influence of manganese deficiency and toxicity on isoprenoid syntheses

Twenty-eight day old wheat (Triticum aestivum L. cv Stacy) response to varying Mn concentration (10.1-10,000 micromolar) in nutrient solution was measured. Manganese concentrations in the most recently matured leaves (blade 1) were 0.21 to 19.03 mmol Mn per kilogram dry weight, respectively. Fresh and dry weights increased to a maximum at the 5 micromolar Mn nutritional level (0.37 millimole Mn per kilogram dry weight) and were decreased at Mn above and below this concentration. Blade 1 chloroplast pigment concentrations increased up to the 20 micromolar Mn nutritional level (1.98 millimole Mn per kilogram dry weight) and decreased at higher Mn concentrations. Thylakoid Mn content was above 1 mole Mn/100 mole chloroplast at Mn nutrition levels which resulted in greatly decreased plant growth. Total phytoene biosynthesis was decreased by Mn deficiency and toxicity. In vitro ent- kaurene synthesis was greatly influenced by Mn concentration with a maximal biosynthesis at 1 micromolar Mn and decreases at Mn levels above and below this concentration. In vivo blade 1 gibberellic acid equivalent concentrations were maximal at 20 parts per million Mn nutrition solution levels (1.98 millimole Mn per kilogram dry weight) and decreased at Mn tissue concentrations above and below this value; additionally, gibberellic acid concentrations were reciprocal to extracted C₂₀ alcohol concentrations. Mn influence on gibberellin and chloroplast pigment biosyntheses exactly matched the measured changes in growth.     

Low iron diet and parenteral cadmium exposure in pregnant rats: the effects on trace elements and fetal viability

The effects of latent iron deficiency combined with parenteral subchronic or acute cadmium exposure during pregnancy on maternal and fetal tissue distribution of cadmium, iron and zinc, and on fetal viability were evaluated. Timed-pregnant Sprague-Dawley rats were fed on semisynthetic test diets with either high iron (240 mg kg) or low iron (10 mg kg), and concomitantly exposed to 0, 3 or 5 mg cadmium (as anhydrous CdCl₂) per kilogram body weight. Animals were exposed to cadmium from gestation day 1 through 19 by subcutaneously implanted mini pumps (Subchronic exposure) or on gestation day 15 by a single subcutaneous injection (Acute exposure). All rats were killed on gestation day 19. Blood samples, selected organs and fetuses were removed and prepared for element analyses by atomic absorption spectrometry. Low iron diet caused decreases in maternal body weight, maternal and fetal liver weights, placental weights and tissue iron concentrations. By cadmium exposure, both subchronic and acute, tissue cadmium concentrations were increased and the increase was dose-related, maternal liver and kidney zinc concentrations were increased, and fetal zinc concentration was decreased. Cadmium concentration in maternal liver was additionally increased by low iron diet. Acute cadmium exposure caused lower maternal body and organ weights, high fetal mortality, and decreased fetal weights of survivors. In conclusion, parenteral cadmium exposure during pregnancy causes perturbations in essential elements in maternal and fetal compartments. Acute cadmium exposure in the last trimester of gestation poses a risk for fetal viability especially when combined with low iron in maternal diet.     

Long-term follow-up after relapses in children with Hodgkin's disease

In the years 1969-1980, 68 children with Hodgkin's disease were subjected to a combined MVPP and radiotherapy. Remissions were obtained in 64 patients, and relapses occurred in 11 children. The treatment of relapse consisted in administration of B-DOPA alone or alternatively with MVPP combined with radiotherapy (in 7 out of 11 patients). The patients were recycled every 2-3 weeks which, with other modifications of chemotherapy, allowed for the completion of the six first cycles within the period of 4,5 to 7 months. A relapse caused death of one child, and two others demonstrated further relapses. At present eight children have been showing disease-free survival following a relapse for the period of 29+ to 152+ (median, 94.5 months). The authors concluded that in patients with relapses of Hodgkin's disease the decisive role rests upon aggressive chemotherapy (high frequency of cycles).     

Pattern and cost of weight gain in previously obese women

Weight gain is common among postobese individuals, providing an opportunity to address the cost of weight regain on energy expenditure. We investigated the energy cost of weight regain over 1 yr in 28 women [age 39.5 +/- 1.3 (SE) yr; body mass index 24.2 +/- 0.5 kg/m(2)] with recent weight loss (>12 kg). Body composition, total energy expenditure (TEE) using doubly labeled water, resting metabolic rate (RMR), and thermic effect of a meal (TEM) were assessed at 0 and 12 mo. Metabolizable energy intake (MEI) was calculated from TEE and change in body composition. Fourteen women had a weight gain of 13.2 +/- 2.1 kg. Twelve-month cumulative excess MEI, calculated as the intake in excess of TEE at month 0, was 749 +/- 149 MJ. Of this, 462 +/- 83 MJ (62%) were stored as accrued tissue, and 287 +/- 72 MJ (38%) was increased TEE. Expressed per kilogram of body weight gain, the energy cost of weight gain was calculated to be 54.8 +/- 4.6 MJ/kg. Interestingly, weight regain time courses fell into three distinct patterns, possibly requiring varying countermeasures.     

Zoledronic Acid Therapy of Patients With Paget Disease of Bone Resistant to or With Unsustained Remission Following Prior Bisphosphonate Therapy

Objective: To evaluate the effect of zoledronic acid (ZA) in patients with Paget disease (PD) who had not had a biochemical remission with prior bisphosphonate therapy or had a remission ≤12 months.Methods: The effects of ZA therapy were studied in 14 patients aged 54 to 90. Serum alkaline phosphatase (ALP) levels were elevated to at least 40% above the normal reference range, and glomerular filtration rates (GFRs) were ≥40 mL/minute. ZA (5 mg) was infused over 15 minutes. ALP and urine N-telopeptide/creatinine (NTx/Cr) were obtained before therapy and at 3, 6, 9, and 12 months, and thereafter at 4-month intervals.Results: At baseline, ALP ranged from 141 to 1,009 U/L. In 13 patients, ALP fell to normal following ZA administration. Remissions occurred in 9 patients who had not previously had a remission. Remissions varied from 12 to 60 months and were more prolonged in 4 patients with prior remissions ≤12 months. ZA failed to induce a remission in 1 patient. Ten to 12 days after therapy in 3 asymptomatic patients, serum calcium levels fell to 7.9, 8, and 8.3 mg/dL. Other than flu-like symptoms in 3 patients after ZA infusion, there were no other adverse effects.Conclusion: Therapy with ZA induced remissions in 13/14 patients and induced more prolonged remissions in patients who previously had remissions ≤12 months. The lack of remission in 1 patient despite 2 courses of therapy is evidence of a continuing therapeutic challenge for some patients with a more resistant form of PD.Abbreviations: ALP = alkaline phosphatase Cr = creatinine NTx = N-telopeptide 25-OHD = 25-hydroxyvitamin D PD = Paget disease ZA = zoledronic acid     

One size does not fit all: Factors associated with increased frequency of radiation overexposure alerts based on fixed-alert thresholds

ObjectivesQuantify the expected rate of CT radiation dose alerts for three body regions using accepted radiation dose benchmarks and assess key determinants of alert frequency.MethodsThis IRB-approved retrospective cohort study evaluated consecutive CT examinations performed between July and December 2013 within an academic medical system. CTDI_vol x-ray tube output metrics were compared to the body-region-specific benchmark levels, Achievable Doses (AD), Diagnostic Reference Levels (DRL), and Dose Notification Values (DNV). A logistic regression model for the simulated alerts was fit as a function of the independent predictors: scanner, body region, gender, weight, and age.ResultsFor 17,000 exams, the proportion of events triggering alerts increased with patient weight. Significant covariates were scanner, body region, patient weight and patient age (all p < 0.0001). Odds of alert generation for the AD, DRL, and DNV benchmarks increased by 7.6%, 6.6% and 2.9% per kilogram, respectively, and by 0.8%, 1.1% and −2.7% per year of age (all p < 0.0001). Compared to the most highly optimized scanner, odds of alert generation varied by a factor of 595 for AD, 1126 for DRL, and 13 for DNV.ConclusionAlert frequency was significantly correlated with weight, age, body region and scanner. Controllable factors include scanner functionality and associated protocol optimization. Patient factors driving alert frequency are predominantly weight, and to a lesser degree, age. Size-agnostic fixed dose thresholds can frequently produce false positive alerts in appropriately performed exams of large patients, while missing opportunities to identify outlier scans of higher-than-expected dose in small patients.     

Scaling Vo2 Peak in Obese and Non‐obese Girls

Objective: The conventional ratio method (milliliters O₂ per mass) typically is used to express Vo ₂ peak. The goal of the current study was to compare Vo ₂ peak of obese girls with normal‐weight girls by ratio and allometric scaling methods. Research Methods and Procedures: We compared Vo ₂ peak by ratio and allometric methods in 46 obese and 47 normal‐weight girls. Indirect calorimetry was used to measure Vo ₂ peak during either treadmill running or walking. Regression analysis was used to determine coefficients for mass and stature for each group with ANOVA used to compare data between groups. Results: The obese girls were taller and had higher values of body fatness (p ≤ 0.05). Absolute Vo ₂ peak (liters per minute) was similar between groups ; however Vo ₂ peak relative to mass was 50% lower (p ≤ 0.05) in the obese girls. When Vo ₂ peak (milliliters per minute per kilogram) and mass were correlated, r = ?0.48 was found in the obese group. Allometric scaling of logarithmic transformed stature and mass reduced this to r = ?0.002, thus eliminating the bias associated with the ratio method. Adjusting Vo ₂ peak allometrically scaled for mass, stature, and the combination of mass and stature reduced the difference between groups from 50% (ratio method) to 10% to 11% (p ≤ 0.05) with higher values found in the normal‐weight girls. Discussion: These results demonstrate the bias associated with the ratio method when comparing Vo ₂ peak in obese girls with Vo ₂ peak in normal‐weight girls. Allometric scaling eliminated the bias and thus may reflect a truer comparative response.     

Clinical use of rubomycin in neuroblastoma in children]

The results of treatment of 23 children at the age of 7 months to 11 years suffering from neuroblastoma are presented; 22 patients with tumors, relapses or metastases were subjected to the treatment and 1 child was treated prophylactically after radical operation. Four patients were subjected to roentgen therapy in addition to the treatment with rubomycin. The antibiotic was administered intravenously in doses of 0.7--1.5 mg/kg in 1--3 days or daily. The caurse dose (3--12 mg/kg) was determined by the treatment efficiency and the side reactions. The objective effect was observed in 68 per cent of the patients, including the pronounced objective effect (marks 3 and 2) in 41 per cent of the cases. Leucopenia (less than 4000 cells in 1 mm3 of the blood). thrombocytopenia, vomiting (or nousea) and changes in the ECG were registered in 20 (87 per cent), 4,9 and 2 patients respectively. When the results of the treatment were positive, repeated courses of the therapy within 1.5--2 years were carried out; 18 patients died within 4 months to 2 years after the first course of the treatment with rubomycin because of the disease development. No signs of the disease were observed in 4 children with in 3--6 years of observation.