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The MLL gene is frequently rearranged in leukemias, and MLL chimeric proteins generated by chromosomal translocations play crucial roles in leukemogenesis. Targets of murine Mll include HOX proteins that regulate body pattern formation and hematopoiesis. However, it is not known whether or not the MLL chimeric proteins regulate the HOX gene expression in human leukemia. To address this issue, THP-1 cells, a human leukemia cell line expressing MLL-AF9, were treated with antisense oligodeoxyribonucleotide (ODN) complementary to the coding sequence of the MLL-AF9 junction. Down-regulation of the MLL-AF9 transcript was accompanied by the reduced expression of the HOXA7 and -A10 genes, but not of the HOXA2, -A4, -A5, and -A9 genes. The number of viable cells cultured with 20 microM antisense ODN for 5 days was 10-fold lower than that of the sense ODN-treated control. And the number of the annexin V-/propidium iodide- apoptotic cells in the antisense ODN-treated cells after 3 days of culture was two-fold higher than that in the control. Staining of the antisense ODN-treated cells with Hoechst 33258 showed the morphology characteristic to apoptosis. These results indicate that MLL-AF9 regulates the expression of the selected HOX genes as well as prevents the leukemic cells from apoptosis.

To explore the possibility that deregulated HOX gene expression might commonly occur during leukemic hematopoiesis, we compared the relative levels of expression of these and related genes in phenotypically and functionally defined subpopulations of AML blasts and normal hematopoietic cells. Initially, a semi-quantitative RT-PCR technique was used to amplify total cDNA from total leukemic blast cell populations from 20 AML patients and light density cells from four normal bone marrows. Expression of HOX genes (A9, A10, B3 and B4), MEIS1 and MLL was easily detected in the majority of AML samples with the exception of two samples from patients with AML subtype M3 (which expressed only MLL). Low levels of HOXA9 and A10 but not B3 or B4 were seen in normal marrow while MLL was easily detected. PBX1a was difficult to detect in any AML sample but was seen in three of four normal marrows. Cells from nine AML patients and five normal bone marrows were FACS-sorted into CD34+CD38−, CD34+CD38+ and CD34− subpopulations, analyzed for their functional properties in long-term culture (LTC) and colony assays, and for gene expression using RT-PCR. 93 ± 14% of AML LTC-initiating cells, 92 ± 14% AML colony-forming cells, and >99% of normal LTC-IC and CFC were CD34+. The relative level of expression of the four HOX genes in amplified cDNA from CD34− as compared to CD34+CD38− normal cells was reduced >10-fold. However, in AML samples this down-regulation in HOX expression in CD34− as compared to CD34+CD38− cells was not seen (P < 0.05 for comparison between aml and normal). a similar difference between normal and aml subpopulations was seen when the relative levels of expression of meis1, and to a lesser extent mll, were compared in cd34+ and CD34− cells (P < 0.05). in contrast, while some evidence of down-regulation of pbx1a was found in comparing cd34− to CD34+ normal cells it was difficult to detect expression of this gene in any subpopulation from most AML samples. Thus, the down-regulation of HOX, MEIS1 and to some extent MLL which occurs with normal hematopoietic differentiation is not seen in AML cells with similar functional and phenotypic properties.

The RC99 committee of the Japan Society for Mechanical Engineers conducted the benchmark tests on strengths of adhesive joints using different testing methods. The effects of joint configuration, loading mode, adherend yield strength and so on, on the strength and data scatter were investigated using two typical epoxy adhesives. The strengths obtained by various tests were compared with each other. The relationships among strengths of butt, single lap and double lap joints and fracture toughness were given. Thirteen member institutes of the committee participated in this project. The benchmark results allow us to recognize that the joint strengths are strongly affected by the curing process. The key to obtaining the appropriate joint strength, is precise temperature control inside the adhesive layer for curing. Toughened adhesives do not always give higher joint strengths than untoughened adhesives. The yield strength of adherends much affects the observed lap joint strength of adhesives.

The serum level of a scavenging enzyme, manganese superoxide dismutase (MnSOD) was examined in 95 patients with ovarian epithelial malignancy. The MnSOD values were variable according to the differences of surgical stage, histologic type and histological grade. Factors affecting the MnSOD level were statistically analyzed. The stage and histologic type were less effective than the histological grade in determining the serum MnSOD value. The level increased significantly in accordance with the elevation of grade. Although the mechanism remains unclear, the MnSOD determination may be useful in predicting the histological grade of ovarian carcinoma.

The driver assistance system (DAS) is a driver-cooperative type system developed to reduce driver's workload and enhance driving safety. It was verified that the driver's workload is reduced when using the DAS with integrated lateral and longitudinal control, as well as the operational load, driver's heart rate and reaction time. In this report, driver's vital reaction such as the electromyography and the electrodermal activity were measured using an actual vehicle with the DAS in order to verify the influence on driver's workload. The DAS was also verified to decrease the driver's workload in view of the vital reaction.

The use of immunodeficient mice, particularly of the nonobese diabetic/severe combined immunodeficient (NOD/SCID) strain, has allowed detection of very primitive malignant progenitors from patients with acute myelogenous leukemia (AML). To define the sensitivity and reproducibility with which the engraftment of different AML cells can be detected, 61 different samples from patients with newly diagnosed AML representing a variety of cytogenetic and French-American-British (FAB) subtypes were injected into NOD/SCID mice. Eight weeks after intravenous injection of 10(7) AML cells, the average percent of human cells in mouse bone marrow was 13.3%, with 70% of samples showing easily detectable engraftment of CD45(+) cells. AML samples with cytogenetic changes associated with a poor clinical prognosis tended to engraft to higher levels than those with changes associated with a good prognosis. Cells with FAB subtypes M3 and, to a lesser extent, M2, engrafted more poorly (P =.002 and.06, respectively) than those from other subtypes. Intraperitoneal injection of human interleukin-3 and Steel factor thrice weekly for 4 weeks did not enhance the levels of AML cell engraftment. However, AML samples that showed cytokine-independent colony growth in methylcellulose assay or expressed growth-factor mRNA in malignant blasts achieved significantly higher levels of engraftment than those which were cytokine dependent in culture or failed to express cytokine message (P.03 and P.02, respectively). In 6 patient samples, the frequency of NOD/SCID leukemia-initiating cells (NOD/SL-IC) varied from 0.7 to 45 per 10(7) cells, which was 200- to 800-fold lower than the frequency of AML long-term culture-initiating cells (AML LTC-IC) in the same samples. Each NOD/SL-IC will produce more than 10(6) leukemic blasts as well as many AML-CFC and AML LTC-IC as detected 8 weeks postinjection into mice. Serial transplant experiments showed the ability of NOD/SL-IC to maintain their own numbers over at least 3 to 4 weeks in vivo. The ability of these progenitors to self-renew combined with their potential to differentiate to produce large numbers of more mature progenitors and leukemic blasts suggests that the NOD/SL-IC assay identifies leukemic 'stem cells' that may maintain the malignant clone in human patients. The further use of this assay should facilitate studies of AML stem cell biology and the evolution of novel therapeutic strategies.

Autotaxin (ATX) is a newly found autocrine tumor cell motility-stimulating factor. ATX is a member of the ecto-phosphodiesterase I (PD-I)/ nucleotide pyrophosphatase family. PD-Ialpha was found as a brain-type ecto-phosphodiesterase I/nucleotide pyrophosphatase. ATX and PD-Ialpha are alternative splicing products from one gene. ATX stimulates motility of A2058 melanoma cells in vitro; however, it has not been known if PD-Ialpha/ATX is expressed in naturally occurred human tumors. In this study, we examined the expression of the human PD-Ialpha/ATX gene in human neuroblastoma tumor tissues and the motility stimulating activity of recombinant ATX on neuroblastoma cells and investigated its transcriptional regulatory mechanism in a human neuroblastoma cell line. The PD-Ialpha/ATX gene was expressed in the primary tumor tissues from neuroblastoma patients to varying degrees. This gene is also expressed in the SMS-KAN neuroblastoma cell line. We identified both isoforms, PD-Ialpha and ATX, in these tumor tissues and SMS-KAN cells. The recombinant ATX stimulated the motility of SMS-KAN cells at low nanomolar concentration. We situated the promoter region, which is essential for its transcription in SMS-KAN cells, at -287 to -254 nucleotides by the promoter activity assay. The gel-shift assay revealed that there exists a nuclear protein in SMS-KAN cells that binds this region. These new insights about autocrine tumor cell motility-stimulating protein will help us to understand the metastatic mechanism of human neuroblastoma.

We investigated the therapeutic efficacy and safety of cefpirome sulfate (CPR) in treatment of hematopoietic disorder-associated infections. A total of 219 patients were admitted to 12 hospitals of Hanshin Study Group of hematopoietic disorders and infections between April 1994 and March 1996 and were enrolled in this study. Most patients received intravenously infused CPR at a dose of 1 or 2 g twice a day for 3 days or more. Twenty nine patients dropped out or were excluded and remaining 190 patients were adopted for the evaluation. A overall response rate was 58.4% (111/190). Among neutropenic patients, the response rate was 50% (8/16) in patients whose peripheral neutrophil counts (PNC) remained less than 100/microliter throughout the observation period and was 53.7% (22/41) in patients with PNC remained less than 500/microliter. In contrast, in patient whose PNC was below 500 before the treatment but exceeded 501/microliter during of at the end of the treatment, the response rate was as high as 78.4% (29/37). When G-CSF was combined, the response rate became significantly (P0.05) higher, 68.5% (50/73), as compared with that, 52.1% (61/117), in patients without it. In cases in which the causative organisms could be identified, the organisms were eliminated in 81.8% (9/11) of the patients infected with Gram-positive bacteria, whereas in 100% (12/12) in those infected with Gram-negative bacteria. Skin eruption developed in 6 patients during the treatment with CPR, and vascular pain and parosmia in one each other. These symptoms subsided soon after discontinuation or even without discontinuation of CPR. Abnormal laboratory findings, mainly liver dysfunction, i.e. elevation of slight degree of serum transaminase levels, were observed. The values, however, turned to normal immediately after the cessation or completion of the treatment. In conclusion, CPR is considered to be an antibiotic of value with high efficacy and safety in treatment of hematopoietic disorder-associated infections.

Blood erythropoietin (EPO) concentration was measured by radioimmunoassay in 513 patients with various diseases. Untreated polycythemia vera showed lower EPO concentration than normal. Aplastic anemia (AA) revealed the highest EPO level among all anemic diseases in relation to hematocrit value. EPO level of AA patients who underwent bone marrow transplantation was as low as normal subjects even when the anemia has not fully recovered. Paroxysmal nocturnal hemoglobinuria (PNH) showed unusually high EPO concentration among hemolytic anemias. In normal subjects, blood EPO concentration showed a diurnal rhythm that was higher at night than during the daytime. These findings suggest the diagnostic usefulness of measurement of EPO in blood diseases.

With a newly developed short term enzyme linked immunosorbent assay kit (TOYOBO Co.), in which 2 kinds of anti-EPO monoclonal antibodies were used, we assayed EPO concentration in sera from patients with renal failure and hematological disorders. In this report, the EPO data were analysed in relation to serum iron concentrations, with ferritin and UIBC. In the patients with renal failure, there was no significant correlation between EPO concentration and serum iron, ferritin, nor UIBC concentration. On the other hand, in the patients with hematological disorders, there were two types. One was in patients with iron deficiency anemia, whose serum EPO was negatively correlated to serum iron (r = -0.64) and ferritin (r = -0.59), but positively related to UIBC (r = 0.27). The another was the pattern in patients with aplastic anemia, leukemia and MDS, whose serum EPO positively correlated to iron and ferritin but negatively correlated to UIBC. In the patients with aplastic anemia serum EPO had good correlation to serum iron (r = 0.62), ferritin (r = 0.60) and UIBC (r = -0.46). The relationship of EPO to iron in the patients with leukemia (r = 0.54), and EPO to ferritin in the patients with MDS (r = 0.42) show significantly positive correlation coefficient.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum erythropoietin (EP) concentration was measured by the recombinant EP-based radioimmunoassay and was examined to standardize the hemoglobin (Hb) related level of 144 normal control and 56 patients with iron deficiency anemia and hemolytic anemia excluding paroxysmal nocturnal hemoglobinuria. The standardization was achieved by logarithmic regression of the EP titier on Hb either by the two-phase linear form or by the third degree sigmoid form at a 95% confidence limit for each regression. The third degree regression was found to be preferable from the view point of both statistics and the negative feedback mechanism. The average and scattering of the deviation from the standard level thus determined of the disease groups indicated that the EP level is: (1) 12 fold higher than the standard level in 42 aplastic anemias (the most in excess and a few in standard). (2) three fold higher than that in 27 myelodysplastic syndromes (relatively higher dispersed state). (3) 29% of the standard level in 33 anemias associated with chronic renal failure (deficient state). (4) 105% of the extrapolated standard level in 22 polycythemia veras (standard state). The standardization of Hb-related Ep titer may provide new pathophysiological approaches in a variety of hematopoietic disorders.

With a newly developed enzyme linked immunosorbent assay kit TOYOBO Co. in which 2 anti-EPO monoclonal antibodies were used, we assayed EPO concentration in sera from normal adults, 168 patients with renal failure and 333 patients with hematological disorders. In the patients with renal failure, serum EPO level was normal (52.9%) or reduced (42.9%), and there was no correlation to their hematocrits. However, there was an increment in EPO concentration correlated to their severity of anemia in the most patients with hematological disorders, such as iron deficiency anemia (correlation coefficient r = -0.74), aplastic anemia (r = -0.89), leukemia (r = -0.81), and MDS (r = -0.65). On the other hand, EPO concentration in sera from all the untreated patients with polycythemia vera were significantly low level. But the concentrations of EPO from the patients successfully treated, with normal hematocrit were recovered to normal level. In the patients with secondary polycythemia, there were much varieties in EPO level. Assay of EPO in blood is important not only for diagnosis of polycythemia but also for the analysis of anemia and clinical use of EPO in vivo. The method described here is accurate and technically not complicated, and could be widely induced in most laboratories.

Cefuzonam (CZON) was used to treat severe infections in 151 patients with hematopoietic disorders, and its efficacy and safety were assessed. The drug was given in doses of 2.0 to 6.0 g a day, divided into 2 or 3, intravenously by injection or infusion. The clinical effects were excellent in 34 cases, good in 40 cases, fair in 5 cases, and poor in 57 cases. Therefore, the results were excellent or good in 54.4% of the patients treated. The efficacy rates were 43.8 and 35.9% for groups of patients whose neutrophil counts were 500/microliters or less and 100/microliters or less, respectively. It was excellent or good in 70.6% of patients in whom causative agents were identified, and in 66.7 and 80.0% of patients infected with Gram-negative and -positive bacilli, respectively. The efficacy rate for patients infected with unidentified agents was 52.1%. The rate for patients who had received other antibiotics previously was 41.5%. The rate for patients having received only one antibiotic for the preceding treatment was 50.0%. Six (3.9%) of the treated patients experienced adverse effects including changes in laboratory test results observed in 4.

The efficacy and the safety of meropenem (MEPM), a newly developed carbapenem antibiotic, were investigated in 150 patients with severe infections complicated with hematopoietic disorders. 1. Clinical responses in 132 patients who were evaluable for effectiveness were excellent in 33 patients, good in 45, fair in 10 and poor in 44, with an efficacy rate of 59.1%. 2. The efficacy rate in patients who had previously been treated with the other antibiotics was 51.2%, while that in patients who had not been thus treated was 62.9%. 3. The efficacy rate in patients whose neutrophil counts increased during the therapy with MEPM was higher than that in patients whose neutrophil counts did not increase. The efficacy rate in patients whose neutrophil counts during the therapy were below 100/mm3 was 48.1%. 4. Out of 150 cases, side effects were observed in 4 patients, 3 with eruption and 1 with jaundice. Abnormalities in laboratory test results on liver functions were noted in 8 patients. These results indicate that MEPM is an effective and safe antibiotic for the treatment of severe infections in patients with hematopoietic disorders.

Twenty-nine adult patients with acute lymphocytic leukemia (ALL) were treated with combination chemotherapy consisting of behenoyl-ara-C, adriamycin, cyclophosphamide, vindesine and prednisolone (BHAC-ACVP regimen). Complete remission (CR) was obtained in 7 of 13 (54%) of the previously untreated, and 4 of 16 (25%) of the previously treated patients. Six of 10 (60%) L1 and 5 of 17 (29%) L2 patients achieved CR. Side effects such as nausea, GPT elevation and fever were observed, but these were not severe in most cases. The result indicates that BH-AC is useful for the treatment of adult patients with ALL.

High-dose intravenous immunoglobulin (IVIG) for idiopathic thrombocytopenic purpura (ITP) produces a dramatic and substantial increase in platelet count, but the increased count tends to return rapidly to its pretreatment level. We studied the effects of immunosuppressive treatment aimed at the maintenance of platelet counts following the IVIG administration in ITP. Thirty-five patients with ITP were treated with IVIG, and then thirty-two of them with an immunosuppressant (azathioprine) and a glucocorticoid (prednisolone). After IVIG, the platelet count increased significantly. With immunosuppressive therapy after IVIG, most patients had a tendency to maintain the counts. In particular, this maintaining effect was remarkable in those patients who had been responsive to the standard prednisolone therapy while non-responders to the prior prednisolone failed to maintain the counts. When prednisolone was given after IVIG, the effect of maintaining platelet counts was dose-dependent. The treatment with azathioprine and prednisolone after IVIG appears to be effective in maintenance of platelet counts.

This study showed several accumulated data through ten years from our experience in hematopoietic disorders and associated infections, which has been analyzed by the Hanshin Study Group of Hematopoietic Disorders and Infections. Since 1979 to 1988, our group had evaluated the sorts of causative organisms and the efficacy of various antibiotics therapy in 2119 cases of infectious diseases associated with hematopoietic disorders. On behalf of evaluating the changes of disease profile for ten years, we divided the accumulated data into three phases; former phase the first three years, middle phase the second three years and late phase the last four years. There was no significant difference in the frequency of various hematopoietic disorders among the three phases. Each leukemia patients occupied 77% of all cases. Sepsis suspected is the most frequent infectious disease accounting for 68.8%. The other infectious diseases were 8.4% of the sepsis, 14.8% of the respiratory infections and 3.1% of the urinary tract infections. Comparing the frequency of infections among the three phases, the respiratory and urinary tract infections inclined to decrease. Of the 532 strains isolated from 2119 cases and identified as causative organisms, gram-negative bacilli occupied 62.8% and gram-positive bacteria 36.5%. In comparing the percentage of gram-negative bacilli among the three phases, it showed a decreasing tendency in order former phase 63.6%, middle phase 76.4% and late phase 43.8%. Pseudomonas, however, had been isolated at almost constant ratio through ten years. On the other hand, the ratio of gram-positive bacteria isolated were 34.5% in former phase, 23.6% in middle phase and 56.3% in late phase, showing increasing a tendency through the period. Twenty-three kinds of antibiotics were administered by intravenous drip infusion. The efficacy rate was 43.9% to 67.2%. In particular, effectiveness of antibiotic therapy often depends on the change of peripheral neutrophil counts from the onset and during the therapy. The efficacy rate, however, was 36% even neutrophil counts have not shown the tendency of increase from less than 100/microliters.

Twenty nine patients completed a pain index card for the first 14 days following placement of an archwire. The index card divided the day into morning, afternoon and evening sessions and the patients were asked to score on a 0-3 basis of the severity of discomfort caused to the teeth (score 0: no discomfort, score 1: discomfort, score 2: mild pain, score 3: severe pain). Results were as follows: 1) All patients suffered discomfort and/or pain following placement of an archwire (discomfort: 10.3%, mild pain: 72.4%, severe pain: 17.2%). 2) There was no significant difference in the pain experience among the three age groups (under 12, 13 to 19 and over 20 years of age). 3) There was statistically significant difference in the pain experience between the sexes. 4) There was no significant difference in the pain experience among the four kinds of archwires (0.0175" braided wire, 0.012" stainless steel wire, 0.016" and 0.016" x 0.022" nickel titanium alloy wire). 5) The discomfort experience was observed in 37.9% and the mild pain experience was in 3.4% of the cases immediately after placement of the archwire. 6) The pain experience was observed in 62.1% of the cases by the end of the day. In 20.7% the pain experience was observed the next day and the pain experience was observed after 2 days in 3.4%. 7) In the severe pain group, the mean value of the pain experience was 4.4 days and that of the discomfort experience was 8.2 days.(ABSTRACT TRUNCATED AT 250 WORDS)

This paper deals with the effect of an intermediate lateral spring support on the stability of a cantilevered tubular pipe conveying fluid. The governing equation of motion is cast into a matrix form by applying the Galerkin method. In the flutter analysis the material damping is taken into account. Comparisons are made between the theoretical and experimental results. It is shown that providing the cantilevered pipe with a spring support does not necessarily lead to stabilization and indeed is likely to have a destabilizing effect. In respect to its location a spring support at the free end may be most destabilizing. The stabilizing effect due to a spring can be caused by transition of the instability mechanism from flutter to divergence.

Vibration and stability of elastic columns subjected to uniformly distributed follower forces are investigated by means of the finite difference method for six typical cases of boundary conditions. A system of k finite difference equations is made of compact form by introducing the concept of a transfer matrix. The behavior of the eigenvalue curve is demonstrated in detail for various values of non-conservativeness parameter of the applied force. Precise stability maps are obtained from the eigen value analysis which determines the divergence and flutter limits.

Describes a new read-only memory (ROM) with minimum geometry. A cascade ratioless circuit configuration is used, which is process compatible with silicon-gate metal-oxide semiconductor (MOS) large-scale integration (LSI) using depletion load MOSTs. The content of a memory cell in the new ROM is determined by the choice of the MOST threshold mode, either an enhancement or depletion mode; this differs from the conventional ROM structure where the content of a memory cell is distinguished by the thickness of gate oxide. The size of a single bit of the ROM is only 196 /spl mu/m/SUP 2/ and is a reduction of 45 percent compared to a conventional silicon-gate ROM.

The peculiar features of instability of Dzhanelidze's model, which is composed of a massless flexible bar and a concentrated mass at the tip and is subjected to a tangential follower force at the tip, are considered. By discussing the eigenvalue curves of Pfluger's model, which has distributed mass in addition to the case of Dzhanelidze's model, and of the corresponding discrete model, it is shown that the critical value, which one must use the dynamic method to obtain, can be identical with the classical Euler value obtainable by the static method only as a result of ignoring a crucial mass. The mathematical meaning of the infinitely large critical frequency is pertinently interpreted.

The basic properties of a new high H c gamma ferric oxide (γ-HY) exhibiting coercive force as high as 450 ∼ 470 Oe were compared with those of conventional gamma ferric oxide (γ-LOP). The average axial ratio was 9 : 1 and the average number of pores was 0.2 per one particle for γ-HY. The pigment volume concentration was 15% increased and the gloss of tape surface 25% improved for γ-HY in the same tape formulation. The squareness ratio was 8% larger and the switching field distribution 25% narrower for γ-HY. The improved dispersibility and orientability were directly observed from the scanning electron micrograph for γ-HY tape.

This study was designed to evaluate the usefulness of Coenzyme Q10 (CoQ10) in the prevention of side effects due to anthracycline agents-Adriamycin (ADM) and Daunorubicin (DNR)-by comparing the preventive effect between CoQ10-treated and non-treated groups. The subjects were 79 patients, 55 of whom had malignant lymphoma. The age range was from 16 to 77 years with a mean age of 45.4 years. CoQ10 was administered by intravenous drip at 1 mg/kg/day the day before ADM or DNR administration, on the day and for a further 2 days after administration. In mean total dose, complete remission rate and mortality, no significant differences were observed between the 2 groups. Although there were also no significant differences in the degree of alopecia, fever, nausea and vomiting, the incidences of diarrhea and stomatitis were significantly (p less than 0.10 and p less than 0.05, respectively) reduced in the CoQ10-treated group. Depression of ST waves (more than 0.05 mV) and changes in T waves (R/10 greater than T, flat, inversion) on ECG were regarded as a parameter of aggravation. Such ECG aggravation was found in 20 of 40 patients given CoQ10 (50.0%) and in 18 of 25 receiving none (72.0%); a cardiotoxicity-inhibiting tendency was thus evident (p less than 0.10). In heart rate, tachycardia was noted in the nontreated group when the period of use of anthracycline agents exceeded 8 weeks. Twenty nine patients received ADM or DNR for 8 weeks or more, and, of them, 17 were treated with CoQ10; 11 of the 17 (64.7%) showed ECG aggravation, while 11 of 12 patients (91.7%) not treated with CoQ10 showed ECG aggravation. A tendency to depress ECG aggravation was thus observed in the treated group (p less than 0.10).

Fosfomycin (FOM) was administered intravenously to 65 cases of severe infections complicated with 62 cases of several haematological disorders. Out of 65 cases, 45 were treated with high doses FOM, i.e., 8 g per day or more. Another 20 cases were treated in usual doses of 4--6 g per day. Causative organisms were isolated from 52 cases of which 32 cases were Gram-negative bacilli and 19 cases were Gram-positive cocci. The effective rate of FOM was 57.8% in the high-dose treatment group (26/45) and 45.0% in the usual-dose treatment group (9/20), but the significant difference was not defined. Among 32 cases with Gram-negative bacilli infections, including Pseudomonas aeruginosa or Serratia marcescens, 15 cases were effective (47%). On the contrary, 14 out of 19 cases with Gram-positive cocci infections were effective (74%). Thirteen cases (50.0%) were effective even in which neutrophils were less than 500/cmm before FOM administration. Severe side effects were not observed, without 2 cases. One was skin eruption due to drug allergy and the other was suspected to be interstitial pneumonitis, but not confirmed pathologically. These data suggest that high dose treatment of FOM were useful for the severe infections even in neutropenic state in haematological disorders.

In atrial fibrillation, it is known that hemodynamics vary according to the preceding R-R intervals. However, the informations of blood flow dynamics have not been available because of the methodological limitations. In this study, blood flow dynamics of atrial fibrillation were assessed using pulsed Doppler echocardiography. The subjects were 160 consecutive patients with atrial fibrillation and without left ventricular asynergy. Using a commercially-available pulsed Doppler instrument (Aloka SSD-910), blood flow patterns in the left ventricle were investigated from the apical long-axis view. The results were as follows: 1. In 22 of the 160 cases (14%), systolic blood flow in the central or apical region of the left ventricle directed towards the apex (termed "back flow"). 2. In the cardiac cycle with "back flow", the preceding R-R interval was shorter; whereas it was longer when "back flow" was absent (591 +/- 103 vs 817 +/- 179 msec, p less than 0.01). Moreover, when a long R-R interval (PPI) followed by a short R-R interval (PI) was observed (greater PPI/PI ratios), the next beat showed distinct "back flow". 3. Left ventricular ejection fraction decreased significantly in patients with "back flow" compared to those without it (42 +/- 15 vs 66 +/- 12%, p less than 0.01). 4. On left ventriculography, the motion of the base of the heart was preserved; however, with "back flow", the motion of the apical area was abnormal, extending towards the apex along the longitudinal axis. 5. Left ventricular ejection flow at the outflow tract disappeared in 13 of the 22 cases with "back flow" in cardiac cycles with short preceding R-R intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefoxitin (CFX) at a daily dose of 3 to 12 grams was administered to patients who had hematopoietic disorders as underlying diseases and having severe infections. Efficacy and safety of the drug were evaluated. The underlying diseases in the 64 patients included in the evaluation of efficacy were acute myelocytic leukemia (30 cases), acute lymphocytic leukemia (9), acute promyelocytic leukemia (3), acute monocytic leukemia (2), chronic myelocytic leukemia-blastic crisis (10), erythroleukemia (2), malignant lymphoma (2), aplastic anemia (2), and others (4). The infections were septicemia in 3 patients, suspected septicemia in 47, respiratory tract infections in 7, oral infections in 3, urinary tract infections in 2, and others in 2. The clinical efficacy of CFX was 'excellent' in 13 patients, 'good' in 26, 'fair' in 6, 'poor' in 19 for an efficacy rate of 60.9%. The efficacy rate classified according to infections was 66.7% in septicemia, 66.0% in suspected septicemia, 42.9% in respiratory tract infections and 66.7% in oral infection. The organisms isolated from the patients with septicemia were E. coli in 2 patients and B. cereus in 1. B. cereus was not susceptible to CFX. The efficacy rate was 60.0% in the 10 patients whose causative organisms were identified and 61.1% in the 54 patients whose causative organisms were not identified. There was no significant difference in the efficacy rate between the patients who had failed to respond to prior antibiotic therapy and those treated with CFX from the beginning. The efficacy rates for the former group (23 patients) and for the latter group (41 patients) were 56.5% and 63.4%, respectively. The efficacy rate in patients with an initial neutrophil count less than 500/mm3 (35 cases) and from 501 to 1,000/mm3 (13 cases) were 57.1% and 76.9%, respectively. Side effects which might have been caused by CFX were skin eruptions in 2 patients (2.6%) and transient elevation of GOT and GPT in 1 patient (1.3%) among 76 patients who were evaluated for safety. CFX was considered to be a markedly useful and safe drug in the treatment of patients with hematopoietic disorders who developed severe infections.

Seventy-five patients with severe infection accompanying hematologic disorder, including leukemia and malignant lymphoma, were treated with cefotaxime (CTX). CTX was administered by intravenous drip infusion at a daily dose ranging from 4 to 16 g for terms of 3 to 21 days. The total doses were ranged from 12 to 226 g. The results obtained were as follows: Clinical effects: Excellent in 20 cases, good in 21 cases, fair in 7 cases and poor in 27 cases. The efficacy rate was 54.7% (41/75). Clinical effectiveness on isolated organisms (27 cases): In single infection (21 cases), the efficacy rates were 80% for Gram-positive cocci, including S. aureus and 63.6% for Gram-negative bacilli other than P. aeruginosa. In mixed infection (6 cases), the rate was 50.0%. There were no significant differences in the efficacy rates for those patients who were grouped by the initial number of neutrophil (less than 100, 101--500 and over 501/mm3). There were no significant difference in the efficacy rates for those patients who were grouped by the initial number of lymphocyte (less than 500 and over 501/mm3). Side effects and abnormal laboratory findings: One case of skin rash and 2 cases of elevated GOT and GPT were observed. CTX was therefore considered as a clinically useful antibiotic for the severe infections even in neutropenic state in patients suffering from malignant hematological diseases.

A phase II clinical trial of mitoxantrone in refractory or relapsed malignant lymphomas was conducted by a cooperative study involving 17 institutions. Of 46 patients entered, 33 were evaluable for responses and toxicity. Thirty-one of the 33 had been previously exposed to adriamycin at a median dose of 220 mg/m2 (range 21-489 mg/m2), and two additional patients had each been given THP-adriamycin at a dose of 80 mg/m2 or 4'-epi adriamycin at a dose of 69 mg/m2. Mitoxantrone was administered in 3 different schedules: 8-12 mg/m2, every 3-4 weeks in 23 patients; 4-6 mg/m2, weekly, in 3 patients; and 2-4 mg/m2, for 5 days, in 7 patients. Summarizing the responses obtained in the 3 schedules, there were 2 partial responders among 5 with Hodgkin's disease, while there were 8 complete responders and 4 partial responders among 28 with non-Hodgkin's lymphoma. The overall response rate for all the evaluable patients was 42% with a complete response rate of 24%. The median response duration was 7+ weeks (range 4-27+ weeks) for complete responders and 7 weeks (range 4-46+ weeks) for partial responders. The major toxicity was myelosuppression: leukocytopenia less than 3,000/microliter occurred in 79% of patients, and thrombocytopenia less than 75,000/microliter in 35%. Other toxic effects were minimal, mild nausea and/or vomiting occurred in 39%, and diarrhea in 3%. Possible drug-related liver and renal dysfunctions were observed in 19% and 10%, respectively. The favorable response to mitoxantrone in patients with prior anthracycline antibiotic therapy suggests that the drug is not fully cross-resistant with anthracycline antibiotics, and that this drug is of value in combination with other drugs as a salvage therapy for patients with refractory or relapsed malignant lymphomas.

One hundred and nine patients with infection accompanying hematologic disorders including leukemia and lymphoma were treated with aztreonam (AZT). Of the 90 patients in whom the efficacy could be evaluated, 17 (18.9%) responded markedly and 29 (32.2%) moderately, the effective rate being 51.1%. The efficacy rate classified according to infections was 25% in septicemia, 46.3% in suspected septicemia, 57.1% in pneumonia and 100% in urinary tract infection. The efficacy rate to the Gram-negative bacteria was 78.9% and to the Gram-positive bacteria was 20.0%. In 4 (66.7%) out of 6 patients in whom P. aeruginosa was the causative organism, AZT was effective. The efficacy rate was 52.2% in the 23 patients whose causative organisms were identified and 50.7% in 67 patients whose causative organisms were not identified. There was no significant difference in the efficacy rate between the patients who failed to respond to prior antibiotic therapy (53.6%) and those treated with AZT from the beginning. The initial neutrophil count did not affect the efficacy rate. Side effects which might have been caused by AZT were eruption and fever in 4 patients. Hepatic disorders and eosinophilia were observed in 7 patients. However, the relationship between AZT and these abnormal findings was not established. These results indicate that AZT is an effective and safe antibiotic for the treatment of infections accompanying hematologic disorders.

BHAC-MMP therapy, a combination of behenoyl-ara-C, mitoxantrone, 6-mercaptopurine and prednisolone, was applied to 49 patients with acute leukemia for remission induction. Complete remission was obtained in 6 out of 11 previously untreated patients (55%), and in 16 of 38 pretreated patients (42%). Median duration of complete remission was 41 weeks in previously treated patients, while 67% of untreated patients were still in complete remission. Most frequent side effects other than hematological toxicities were gastrointestinal disturbances, and GPT elevation etc., although most of these were not severe. In conclusion, BHAC-MMP therapy seems to be very promising for remission induction or for possible intensification treatment for acute leukemia.

Seventy-six patients with severe infection accompanying hematologic disorders including leukemia and lymphoma were treated with intravenous drip infusion of cefotetan (CTT). Of the 66 cases in whom the efficacy could be evaluated, 22 cases responded markedly and 16 cases moderately, the effective rate being 57.6%. It is impressed that more cases responded markedly to CTT than to any other antibiotics previously studied. None of the cases revealed serious side effects attributable to CTT. These results indicate that CTT is an effective and safe antibiotic for the treatment of severe infection accompanying hematologic disorders. As CTT was administered to special cases under marked decrease of neutrocyte, the importance of neutrocyte in the treatment of infection was also indicated.