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Biomedical subjects

A Kanamaru

Publications and source records attributed to A Kanamaru.

At least 145 records · Page 8Linked to original sources

Application of long-term bone marrow cultures for studying the leukemic transformation of myelodysplastic syndromes.

Myelodysplastic syndrome (MDS) has been thought to be an identifiable early stage in multistep leukemogenesis. Considerable numbers of patients with MDS eventually develop acute myelogenous leukemia (AML), which is very much more difficult to manage than typical denovo AML. There are several differences in both the clinical and biological behavior of AML with and without prior MDS. We have established an unique long-term bone marrow culture (LTBMC) system which allows abnormal cells to grow in preference to normal cells, based on the method originally described by Dexter et al. Leukemic transformations occur more frequently in MDS patients with abnormal karyotypes, and particularly those with multiple abnormalities. New cytogenetic abnormalities were occasionally observed at the time of transition to AML. We have applied this LTBMC system for cytogenetic and molecular studies on the leukemic transformation from MDS. Among the 32 patients with MDS studied thus far, novel abnormal karyotypes were detected during the LTBMCs in 15 patients. Furthermore, 6 out of 23 novel karyotypes detected during the in-vitro cultures emerged in vivo, one to 11 months later in 4 patients. In addition, point mutation of the N-ras proto-oncogene was observed in 3 of 18 cases. The signal of the dot-blot hybridization was increased in one examined case after 2 weeks in culture. Thus, this LTBMC system may provide some promising information with respect to understanding the multistep process from the preleukemic stage to the development of overt leukemia as well as its prognostic relevance.

Bone Marrow↗

A randomized controlled study of granulocyte colony stimulating factor after intensive induction and consolidation therapy in patients with acute lymphoblastic leukemia. Japan Adult Leukemia Study Group.

To determine the efficacy and optimal daily dose of recombinant human granulocyte colony-stimulating factor (rG-CSF) after intensive chemotherapy, a prospective randomized study was conducted with daily intravenous administration of 2, 5 or 10 micrograms/kg G-CSF after induction therapy, and 0, 2, 5 or 10 micrograms/kg after consolidation therapy, until neutrophil counts recovered to more than 2000/mm3. The subjects were 41 adult patients with newly diagnosed acute lymphoblastic leukemia (ALL). After the induction therapy, neutrophil recovery to more than 1000/mm3 was significantly faster in the 5 (P = 0.047) and 10 micrograms/kg groups (P = 0.011) than in the 2 micrograms/kg group, but did not differ between the 2 former groups. The median days of neutrophil recovery to more than 1000/mm3 were 8.5, 9 and 12 days, respectively. After the consolidation therapy, neutrophil recovery to more than 1000/mm3 was significantly faster in the 2, 5 and 10 micrograms/kg groups than in the no rG-CSF group (P < 0.001, respectively), but did not differ among the 3 former groups. The median days of neutrophil recovery to more than 1000/mm3 were 12, 11, 10, and 23 days, respectively. Febrile neutropenia and incidence of documented infection tended to be less in the 5 and 10 micrograms/kg groups than in 0 and 2 micrograms/kg groups. A dose of 5 micrograms/kg rG-CSF given by a 30 min infusion daily seems to be an effective and optimal daily dose to accelerate neutrophil recovery after intensive remission induction and consolidation chemotherapy in adults with acute lymphoblastic leukemia (ALL).

Adolescent↗

[An evaluation of a therapy with antibacterial and antifungal agents infections with hematological disorders].

The primary objective of this study is to confirm the efficacy and safety of combination therapy with antibacterial and antifungal drugs for patients with hematological disorders complicated with infections of unknown causative organisms. The subjects consisted of 55 patients with hematological disorders, 28 males and 27 females, ranging from 1 to 78 years of age, with an average age of 34 years. The breakdown of the patients by disease was: 41 leukemias, 10 malignant lymphomas, 3 myelodysplastic syndromes and an aplastic anemia. All patients were treated with sulbactam/cefoperazone (SBT/CPZ) and aminoglycoside (AG) plus fluconazole (FLCZ) as an empiric therapy. Overall efficacy rate was 54.5% for all the patients: 57.7% for patients with suspected sepsis and 0% for those with pneumonia from which unknown organisms were detected. The efficacy rate was 59.4% for patient who had been previously treated with other antibiotics and 47.8% for those who had not previously been treated. The above results suggested that this combination therapy might be effective for severe infections of unknown causative organisms associated with hematological disorders.

Adolescent↗

Hematopoietic recovery from host progenitors with normal karyotype devoid of Philadelphia chromosome in a patient with CML after allogeneic BMT.

A male patient with CML received a BMT from his sister and developed chronic GVHD. The host-origin normal karyotype (46,XY) was identified for the first time in the 60th month after BMT. Detection of Y-chromosome-specific DNA in BM and peripheral blood (PB) showed that all BM samples obtained 6 months from BMT were positive for Y-specific DNA, while PB became positive in the 60th month after BMT. The BCR-ABL mRNA derived from leukemic cells was detected in the 36th month post-BMT, but not in the 60th month or thereafter. Fluorescence in situ hybridization revealed that 1.5% and 0.6% in BM and PB cells were Y-positive in the 70th month post-BMT, respectively. DNA analysis of hematopoietic progenitor colonies revealed 1 of 42 erythroid colonies to be host derived. These results indicate that host-origin hematopoietic cells survive chronic GVHD, while the Ph1 clone was eliminated.

Adult↗

[Bone marrow transplantation for refractory anemia].

Each nineteen patients with severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS) have been treated by allogeneic bone marrow transplantation (BMT) at Hyogo College of Medicine between 1980 and 1991. Rejection was one of the major problems for SAA patients. Conditioning regimen including irradiation reduced the rejection rate, but secondary cancers may develop as the dose of irradiation increased. It is practically important to determine the indication of BMT for MDS-refractory anemia (RA). We considered the indication of BMT for those who have abnormal karyotypes and/or life threatening complications. Five out of nine patients with MDS-RA are surviving after BMT. Four out of ten cases with MDS RAEB-T and overt leukemia are alive. BMT should be recommended for patients with MDS who satisfy the above conditions, if suitable donors are available. However, it remains to be determined whether the patients with RAEB or MDS overt leukemia should be treated with chemotherapy prior to the preconditioning for BMT.

Adolescent↗

High serum IL-6 level reflects susceptible status of the host to endotoxin and IL-1/tumor necrosis factor.

Patients with high level of serum endotoxin did not necessarily develop into lethal shock, whereas some patients died of septic shock even when their serum endotoxin levels were low. These results indicate that limiting factor which determines the host to be endotoxin shock principally depends on the host susceptibility to endotoxin instead of serum endotoxin level. To understand this susceptible status of the host to endotoxin, we used Propionibacterium acnes primed mouse endotoxin shock model. We found that P. acnes-primed mice responded to low dose of LPS by enhanced production of IL-1 and TNF. And such mice were highly susceptible to the lethal shock inducing effect of IL-1 and/or TNF, which also induced high level of serum IL-6 in these mice. Therefore, measurement of serum IL-6 level provides us with the information of the preceding exposure of the host to either LPS or IL-1 and/or TNF and the highly susceptible status of the host to these stimuli. Based on these results obtained from animal model, we investigated the relationship between serum IL-6 levels and serum endotoxin levels in the patients with malignant hematologic disorders. We found that these patients fell into two groups; an endotoxin susceptible group, equivalent to P. acnes-primed mice, showing high level of serum IL-6 with low level of serum endotoxin, and a nonendotoxin susceptible group, equivalent to P. acnes-nonprimed mice, showing low or undetectable level of serum IL-6 with high level of serum endotoxin. We propose that the measurement of serum IL-6 level in the patients positive for endotoxin is a useful tool in evaluating diagnosis and prognosis of endotoxin shock.

Adolescent↗

Serum thymidine kinase, a possible marker for monitoring the effect of bone marrow transplant treatment in early recovery phase.

We measured serum thymidine kinase (TK) activity with a radioenzyme assay system employing [I-125]-iododeoxyuridine as the tracer on serial specimens from five bone marrow transplant (BMT) patients before and after transplantation. The serum level of TK activity in the 4 patients with effective BMT treatment ranged from 3.0 to 16.9 U/L (mean, 7.80 U/L) before transplantation and from 27.3 to 236.1 U/L (mean, 82.95 U/L) after the BMT treatment. Mean serum TK activity increased 13.17-fold (range, 1.68 to 29.14-fold). In contrast, the activity in the patient with ineffective BMT treatment was not significantly different during, before, or after BMT treatment. In addition, serum TK activity in BMT patients was well correlated with the change in the number of leukocytes before and after BMT treatment [r = +0.709 (p less than 0.01), y = 0.012 x +0.87]. We conclude that the determination of serum TK activity in BMT patients is very useful in monitoring the course of bone marrow transplantation in the early recovery phase.

Adolescent↗

Detection of latent subclones with abnormal karyotypes by long-term bone marrow cultures in cases of myelodysplastic syndrome.

Cytogenetic studies on non-adherent cells from long-term bone marrow cultures (LTBMC) were done for 23 patients with myelodysplastic syndrome (MDS) and compared with the karyotypes detected during their clinical courses. Of 14 cases with normal karyotype before culture, abnormal karyotypes were detected first in LTBMC from seven. Novel abnormal karyotypes were observed after LTBMC in two of four cases which had had both normal and abnormal karyotypes before culture. Abnormal karyotypes were also newly detected in four of five cases with only abnormal karyotypes before culture. Among 13 cases in which abnormal karyotypes were observed during the cultures, three patients showed the same karyotypes 1-11 months later in their clinical courses. These findings suggest that our LTBMC might be useful for evaluating the prognosis and choice of treatment for MDS patients.

Adult↗

Effect of acupuncture at right Hoku point on the bilateral vibration-induced finger flexion reflex in man.

Vibration applied to the volar side of the finger tip has been reported to induce finger flexion reflex. Acupuncture is reported to inhibit this vibration-induced finger flexion reflex (VFR) in the ipsilateral hand. The purpose of this study was to investigate the effect of unilateral acupuncture in the hand on VFR in both hands. As no systematic study on the relationship between VFR and the force of voluntary contraction with no vibration (Initial Force: IF) has been reported, this relationship was studied prior to the present study on acupuncture. VFR was induced by mechanical vibration on the volar side of the middle finger tip with 10 g to 500 g IF. With approximately 300 g IF, VFR was consistent. Therefore, approximately 300 g IF was applied for VFR induction to study the effect of acupuncture on VFR. A stainless steel needle was inserted into the right Hoku point and remained inserted (in-situ technique) for 10 minutes. VFR in both hands was significantly decreased by acupuncture at the right Hoku point (% control force of VFR: right, 67.8%; left, 74.6%). The present results suggest that acupuncture in the unilateral hand influences the bilateral reflex arc of VFR.

Acupuncture Points↗

Comparison of the survivals between bone marrow transplantation and chemotherapy for acute leukemia in first remission--a Japanese single institution study.

The outcome of sixty-four patients with acute leukemia in first remission who had been treated with either bone marrow transplantation (BMT) or conventional chemotherapy was retrospectively evaluated (a median follow-up of 37 months). Among them, 26 patients (age range; 14-42 years) received allogeneic BMT from HLA-identical siblings and 38 patients (age range; 13-43 years) who had no HLA-identical donors undertook the continued combination chemotherapy. Kaplan-Meier product-limit estimate of actuarial survival of acute myelogenous leukemia (AML) patients was 48.9% for the BMT group and 15.7% for the chemotherapy group (p = not significant, NS). For acute lymphoblastic leukemia (ALL) patients, the survival following BMT was 80.2% and was significantly higher than that of the chemotherapy group of 33.3% (p < 0.05). The disease-free survival of AML and ALL for the BMT group was 34.3% and 36.5%, respectively, which was higher than that of the chemotherapy group (16.7% and 23.4%, respectively (p = NS)). These findings in our Japanese single institution study suggested that BMT may be the treatment of choice for adult patients with acute leukemia in first remission if they had suitable donors and that more effective therapeutic regimens were necessary for patients without compatible donors in order to obtain the longer remission duration.

Acute Disease↗

[Dyspnea and respiratory reflexes].

It has been suggested that afferents from intercostal muscles may play a role in the genesis of dyspnea. In this study, lower intercostal muscles were tapped or vibrated to induce a reflex, evoked potentials, and sensation. The tapping stimulus induced H reflex in the same muscle with a latency of 12 msec. Also the same stimulus induced evoked potentials in the cerebral cortex (N1: 19.8 +/- 1.2 msec). This suggests projection of the intercostal muscle spindle afferents to the cerebral cortex. 100 Hz vibration induced a later component, presumably an event-related potential, at 250 msec after the onset of both the inspiratory and expiratory phase. Thus, it may be possible that intercostal muscle spindle afferents project to the cerebral cortex and play a role in respiratory sensation. It has been suggested that dyspnea is reduced by increasing inspiratory and expiratory intercostal muscle spindle afferents during the inspiratory and expiratory phases, respectively. Thus, stretching the inspiratory and expiratory intercostal muscles during the respective muscular contraction phase may be effective in reducing dyspnea.

Dyspnea↗

[Measurement of busulfan concentration in plasma and spinal fluid from transplant patients pretreated with busulfan and cyclophosphamide].

Busulfan (BU) concentrations in the blood and spinal fluid of 7 patients pretreated with BU for bone marrow transplantation (BMT) were measured using gas chromatography. The data from these periodically obtained samples were used to study the relationship between the BU concentration and complications (e.g. vomiting), indicating that vomiting leads to a lower maximum BU level. The trough level of BU concentration at 6 hours after administration was stable at around 500 ng/ml, not showing little effect of vomiting. The BU concentrations in the spinal fluid were virtually the same as those in plasma collected at the same time and the spinal fluid/plasma ratio of the BU concentration averaged 1.06. No veno-occlusive disease (VOD) was noted. Failure of engraftment occurred in one case of myelofibrosis, however, as the plasma BU concentration in this case was not lower than the others, the graft failure was not considered to be due to the preconditioning regimen including BU.

Adolescent↗

[Interleukin-6 in hematological diseases with septic shock].

The authors measured the level of interleukin-6 (IL-6), endotoxin and CRP from 7 patients of documented sepsis with hematological disorders. IL-6 was higher in patients who developed septic shock, compared with patients who had only sepsis. These data revealed the importance in the level of IL-6, rather than endotoxin and CRP, in managing the patients with septic shock.

Hematologic Diseases↗

[Primary myelofibrosis successfully treated with allogeneic bone marrow transplantation].

A 31-year-old man with primary myelofibrosis initially received low dose Ara C. Splenomegaly decreased but pancytopenia continued. Allogeneic bone marrow transplantation from his sister was then performed. Busulfan and cyclophosphamide were used as a preconditioning regimen, which included neither irradiation nor splenectomy. As the bone marrow was hypoplastic after transplantation, G-CSF was given. It was useful for systemic infection. After transplantation, leukoerythroblastosis and tear drop poikilocytosis disappeared in peripheral blood. Finally, bone marrow fibrosis disappeared and hemopoiesis to normal limits recovered 17 months later. These results demonstrate that bone marrow transplantation is effective for primary myelofibrosis for which there is no otherwise curative therapy.

Adult↗

[Co-operative on salvage chemotherapy with VP-16 for malignant lymphoma. Hanshin Study Group on Treatment for Hematological Disorders].

Forty one patients with refractory malignant lymphoma were treated with a combination of VP-16, ACM, BH-AC, MTX and PDN as a salvage chemotherapy. These patients were either resistant to frontline therapy or refractory in their relapses. Three patients (7%) achieved a complete remission and 14 patients (34%) attained a partial remission. An overall response rate was 41%. Major toxicities were myelosuppression, nausea, and vomiting. However, they were well tolerated. This regimen has been effective in the treatment for the patients with refractory malignant lymphoma.

Aclarubicin↗

[A study of combination chemotherapy (BHAC-ACVP) for adult acute lymphocytic leukemia. Hanshin Co-operative Study Group of Hematological Malignancies].

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.

Antineoplastic Combined Chemotherapy Protocols↗

Clinical effect of BV-araU on varicella-zoster virus infection in immunocompromised patients with haematological malignancies.

We evaluated the treatment of varicella-zoster infection with BV-araU in immuno-compromised patients with haematological malignancies in a randomized controlled study. Comparison was made between doses of 150 and 30 mg/day. For ethical reasons there was no placebo group. The percentage of patients given a 'very effective' rating by both attending physicians and the Evaluation Committee was significantly higher in the 150 mg/day group (56.0%) compared to the 30 mg/day group (15.0%). There was no significant difference in efficacy rate ('very effective' plus 'effective') between the two groups. The incidence of side effects was low (7.8%), all were mild and disappeared on stopping treatment. These results suggest that BV-araU is clinically useful, especially at a dose of 150 mg/day in immunocompromised patients. Further comparative studies between BV-araU and acyclovir or vidarabine are indicated.

Adolescent↗