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Biomedical subjects

M Bessho

Publications and source records attributed to M Bessho.

At least 37 records · Page 2Linked to original sources

New system for assessing the prognosis of refractory anemia patients.

Refractory anemia (RA) is a very heterogeneous disease regarding biological and clinical features. The International Prognostic Scoring System (IPSS) was useful for assessing the prognosis in the whole group of 219 myelodysplastic syndrome (MDS) patients. However, the IPSS was not sufficient in 132 RA patients. To predict survival and freedom from acute myeloid leukemia (AML) evolution, we investigated individual prognostic factors based on the clinical parameters (age, gender, morphologic features, cytopenias and cytogenetics) of 132 RA patients using univariate and multivariate analyses. Based on the results, we devised a new system for assessing the prognosis of RA patients. In our system, RA patients with pseudo-Pelger-Huët anomalies >/=3% were classified as high risk (12 patients); of patients without pseudo-Pelger-Huët anomalies >/=3%, those with intermediate/poor karyotype according to IPSS, Hb </=6 g/dl or mMgk >/=10% were classified as intermediate risk (57 patients); and those without high or intermediate risk were classified as low risk (67 patients). In our system, the analyses of both survival times and leukemia-free survival times revealed significant differences among the three groups (P < 0.0001).

Acute Disease↗

[Non-Hodgkin's lymphoma complicated by recurrent intractable generalized herpes zoster responsive to long-term acyclovir therapy].

A 34-year-old male with a history of chickenpox developed primary abdominal non-Hodgkin's lymphoma (diagnosed in August 1995). Treatment with cyclophosphamide, doxorubicin, vincristine, and prednisolone achieved a partial remission. In July 1996, the disease recurred, and the patient received chemotherapy with carboplatine, etoposide, mitoxantrone, and prednisolone, but no response was noted. Involvement of the central nervous system and meninges was diagnosed on September 12, 1997. Blast cells were detected in the peripheral blood on September 26. Based on these findings, he was diagnosed as having leukemia. On September 27, painless vesicles developed on the left gluteal region. On October 13, the patient was hospitalized because the vesicles had spread over his entire body. Pathologic examination of the roofs of the blisters showed masses of inclusion bodies. Based on this, a diagnosis of varicella-zoster infection was made. Treatment with acyclovir (750 mg/day) for seven days failed to form crusts. New vesicles developed after the drug was discontinued, but crusts formed after acyclovir therapy was resumed. He died of interstitial pneumonia on December 21. Autopsy could not be performed. Histopathologic examination of pulmonary tissue obtained by necropsy did not reveal the presence of inclusion bodies characteristic of herpes simplex or varicella-zoster infection. Varicella-zoster virus (VZV) antigen was negative by an immunochemical staining method using monoclonal antibodies against VZV. Continuous long-term administration of acyclovir has been reported to be effective for non-Hodgkin's lymphoma complicated by recurrent intractable herpes zoster.

Acyclovir↗

[A neutropenic acute myeloid leukemia patient complicated with chronic otitis media due to Aspergillus niger and yeast-like fungi caused by superinfection].

There have been few reports describing otomycosis in association with compromised hosts. So we report a neutropenic acute myeloid leukemia (AML) patient complicated with otomycosis caused by superinfection. A 51-year-old male was admitted because a third relapse of AML in March 1998. Two years ago, he was diagnosed as having chronic otitis media involving the VII cranial nerve due to Pseudomonas aeruginosa coinciding with AML. Then, he had suffered from a right-sided earache and otic discharge in accord with every myelosuppression, which improved on treatment with otic administration of ofloxacin. After 1 course of induction chemotherapy, he developed a spiking fever with severe earache and otic discharge at a nadir period of WBC. Ear swab cultures yielded Aspergillus niger and yeast-like fungi. So, he was treated with intravenous administration of amphotericin B (AMPH-B): initial dose was 5 mg/day and was gradually increased to 30 mg/day. Thereafter, the otic symptoms subsided and never recurred. Subsequently, he was given another antifungal agent, itraconazole. Although induction chemotherapies resulted in failure, he did not suffer otic symptoms until his death due to cerebral bleeding in January 1999. For neutropenic patients without rapid hematological improvement, we recommend intensive antifungal therapy as the first-line of therapy for otomycosis rather than local therapy.

Acute Disease↗

[Atypical chronic myeloid leukemia presenting with trilineage dysplasia and IgG (lambda) type monoclonal gammopathy].

A 78-year-old man was diagnosed as leukocytosis in February 1994. Physical examination revealed marked hepatosplenomegaly. A peripheral blood examination disclosed 95,090/microliter leukocytes without hiatus leukemicus, 6.5 g/dl Hb, and 15.0 x 10(4)/microliter platelets. The neutrophil alkaline phosphatase score was 27, and serum VB12 was above 1,600pg/ml. IgG was identified as monoclonal immunoglobulin of type lambda. Bone marrow specimens demonstrated marked granulocytic hyperplasia. Neither the Philadelphia chromosome (Ph1) nor BCR gene rearrangement was detected; hence, the diagnosis of Ph1 (-) chronic myeloid leukemia (CML) was made. The patient was treated with hydroxyurea and low-dose VP-16 with no improvement, and died of pneumonia and sepsis in June 1995. This case was considered to be consistent with atypical CML (aCML) according to the FAB classification because monocytosis was not observed. It seems likely and interesting that the coexistent monoclonal gammopathy and aCML might have arisen from common abnormal hematopoietic stem cells.

Aged↗

[The importance of WT1 gene expression in the detection of minimal residual disease. A comparison of WT1 AML1/MTG8 transcripts].

The Wilms tumor gene (WT1) has been reported to be a prognostic factor and a marker for the detection of minimal residual disease (MRD) in acute leukemia. Using competitive polymerase chain reaction procedures, we examined the expression of the WT1 gene in acute leukemia patients with several tumor-specific DNA markers, including bcr/abl, PML/RAR alpha, and AML1/MTG8. A strong correlation was observed between the levels of WT1 and PML/RAR alpha expression. However, AML1/MTG8 transcripts were detected at all stages of the disease even when the expression level of WT1 gene was low. From these findings, we concluded that monitoring the WT1 expression level is a useful means of determining the effectiveness of chemotherapy, and that WT1 is an effective marker for the detection of MRD, especially in acute myeloid leukemia patients with AML1/MTG8.

Acute Disease↗

Accelerated entry into S phase associated with up-regulation of cyclin D1 as a mechanism for granulocyte colony-stimulating factor (G-CSF)-induced apoptosis of murine myeloid leukemia cells.

We previously reported that injection of recombinant granulocyte colony-stimulating factor (G-CSF) suppressed the development of leukemia in mice transplanted with C2M-A5 (C2M) myeloid leukemia cells and that the anti-leukemic effect of G-CSF was ascribed to the induction of apoptosis of C2M cells. These observations make a striking contrast with other previous reports on the biological activities of G-CSF. In the present study, in order to further clarify the G-CSF-induced apoptosis of C2M cells, we studied the effects of G-CSF on the cell cycle as well as the molecular events involving D-type cyclines and their cyclin-dependent kinases (cdk) in G-CSF-treated C2M cells. Cell cycle analysis revealed that G-CSF treatment of C2M cells resulted in accelerated entry from the first gap (G1) phase into the DNA synthesis (S) phase. Western blotting disclosed that G-CSF treatment resulted in down-regulation of cyclin D2 and cdk2 and up-regulation of cyclin D1 and cdk4. The reciprocal relationship between the up-regulation of cyclin D1 and down-regulation of cyclin D2 was closely associated with accelerated entry into S phase and subsequent apoptosis of C2M cells. These results suggest that G-CSF-induced apoptosis of C2M cells might be ascribed to imbalanced cell cycle progression due to deregulated expression of D-type cyclins and their cdks.

Animals↗

Therapy-related AML after successful chemotherapy with low dose etoposide for virus-associated hemophagocytic syndrome.

A 19-year-old male patient with virus associated hemophagocytic syndrome (VAHS) began receiving chemotherapy including etoposide (cumulative dose of 900 mg/m2 intravenously) and Ara-C (cumulative dose of 360 mg/m2 intravenously) in July 1994. He achieved complete remission, but developed acute myelomonocytic leukemia (AML, FAB M4) with t(9;11)(p22;q23) in March 1997 and a rearrangement of the MLL gene was also recognized. The MLL gene rearrangement is closely associated with secondary leukemia with an 11q23 translocation. It is highly likely that this case of AML was caused by the cytostatic treatment the patient received, including etoposide for VAHS.

Adult↗

Refractory anemia with severe dysplasia: clinical significance of morphological features in refractory anemia.

Refractory anemia (RA) in myelodysplastic syndromes (MDS) are very heterogeneous diseases regarding their morphology, clinical features and survival. We proposed the new designations 'RA with severe dysplasia (RASD)' and 'RA with minimal dysplasia (RAminiD)'. In our criteria, RASD is considered present if a bone marrow (BM) examination shows Pseudo-Pelger-Huet anomalies of mature neutrophils > or =3% and/or micromegakaryocytes (mMgk) of megakaryocytes > or =10% in RA patients. RAminiD is defined as RA cases other than RASD. After the reclassification of 58 primary RA patients, the group was composed of 45 RAminiD and 13 RASD patients. The blast percentage in the BM and the frequency of cytogenetic abnormalities observed in the RASD patients were intermediate between those in the RAminiD and RAEB patients. The analysis of survival curves revealed differences among the three groups; the RASD patients had lower survival probabilities than those of the RAminiD group, and significantly higher probabilities than those of the RAEB group. (RAminiD vs RASD, P=0.06; RASD vs RAEB, P=0.004.) Our data indicate that in RA patients, RASD is a distinct subset of RA with an unfavorable clinical outcome.

Adult↗

[Two cases of hematological malignancies diagnosed before death as aspergillosis with skin lesion].

We report two cases of aspergillosis with skin lesions. The first involved a 63-year-old female with acute lymphocytic leukemia. In 1992, she received chemotherapy for acute leukemia. Subsequently, she noted swelling of her leg, a skin biopsy was performed and Aspergillus flavus was isolated. The second patient was a 71-year-old male with myelodysplastic syndrome. In 1996, he developed a massive inguinal abscess from which Aspergillus fumigatus was isolated. The prognosis of aspergillosis was poorer in the case with skin swelling than in the one with a massive abscess.

Aged↗

[Clinical efficacy of fosfomycin in combination with sulbactam/cefoperazone in the treatment of severe infections complicated to blood dyscrasia. Working Group of Kanto Combination Therapy for FOM + SBT/CPZ].

In the treatment of severe infections complicated to blood dyscrasia, the efficacy and usefulness of fosfomycin (FOM) in combination with sulbactam (SBT)/cefoperazone (CPZ) were compared between patients receiving FOM in the first followed by SBT/CPZ (Group A) and those receiving both drugs simultaneously (Group B). The following results were obtained. 1. The efficacy rate was 56.3% for Group A and 47.9% for Group B, with no significant difference. 2. The efficacy for patients suspected of the presence of septicemia, the efficacy rate was 57.9% for Group A and 54.3% for Group B, with no significant difference. 3. As for underlying disease, patients with acute myelogenous leukemia were most prevailing. In these patients, the efficacy rate was 57.1% for Group A and 27.3% for Group B, with no statistically significant difference. However, the efficacy rate tended to be higher in Group A. 4. The administration of antibiotics was effective to restore the neutrophil count to 501/microliters or higher in 77.8% and 45.5% of the cases for Groups A and B, respectively, with significantly higher efficacy for Group A. 5. In the safety evaluation a total of 115 cases were included. Side effects and laboratory abnormalities were seen in 3 cases each, but none of them were serious in degree. From these results, it was confirmed that the combination therapy consisting of administration of FOM followed by SBT/CPZ with some interval is effective for severe infections complicated to blood dyscrasia.

Anti-Bacterial Agents↗

[Acute promyelocytic leukemia relapse as leukemia cutis shortly after complete remission with all-trans retinoic acid].

A 56-year-old man was admitted to our hospital in September, 1996. Chromosomal translocation (15; 17) and a PT-PCR study for PML-RAR alpha mRNA were positive in bone marrow aspirates, and acute promyelocytic leukemia was diagnosed. After CR was obtained with all-trans retinoic acid (ATRA) followed up with chemotherapy, the RT-PCR became negative. When he was readmitted in April, 1997, skin eruption on his chest and extremities were observed. Specimens taken for biopsy revealed leukemia cutis, and RT-PCR became positive in the same specimen. Bone marrow PT-PCR was also positive without abnormal promyelocytes. Although he was treated with oral ATRA 80 mg/day again, no significant improvement in leukemia cutis was noted. After combined therapy with Ara-C and acularubicin, skin eruption disappeared and bone marrow RT-PCR became negative. A second CR was then obtained. Although it is unknown whether the administration of ATRA is related to extramedullary relapse or not, we recommend combined chemotherapy for such cases.

Humans↗

[Clinical evaluation of combination therapy with cefpirome and amikacin for infections associated with hematological disorders].

Cefpirome (CPR) and amikacin (AMK) were used concomitantly to treat infections complicated by hematological diseases. A total of 100 subjects were evaluated, and the allover efficacy rate was 72.0%. Acute leukemia was found in the largest number of patient, 55, followed by 12 cases of malignant lymphoma and 6 cases of chronic myelogenous leukemia. By type of infection, patients having suspected sepsis were the largest in number, being 50, and the efficacy rate was 68.0%. The efficacy rates for sepsis and pneumonia were 57.1% (7 cases) and 61.1% (18 cases), respectively. The efficacy rates by neutrophil counts before administration of CPR and AMK and at 7 days after administration were both 71.9% in the group of less than 500/microliter, both 60.0% in the group of less than 100/microliter. The efficacy rate was 75.0% in the group of granulocyte colony stimulating factor (G-CSF) concomitant usage, and 70.0% in the non-concomitant usage group. Concomitant treatment with CPR and AMK exhibited a high level of safety and efficacy rates in infections complicated by hematological diseases and high.

Adolescent↗

[Waldenström's macroglobulinemia effectively treated with chronic daily oral administration of low-dose etoposide].

A 77-year-old woman with complaints of fever and systemic lymphadenopathy was admitted to our hospital on February 16, 1995. Serum IgM was elevated to 2,097 mg/dl. Lymph node biopsy showed diffuse infiltration with lymphoplasmacytoid cells. Thus, she was diagnosed as having Waldenström's macroglobulinemia. Considering her age and congestive heart failure, she was treated with oral administration of low-dose etoposide (25 mg/day). Splenomegaly and superficial lymphadenopathy disappeared after one course of therapy. Until her death due to pneumonia, complete remission continued for one year without any symptoms and adverse effects except for mild diarrhea. Low-dose etoposide therapy was considered to be well tolerated and useful for elderly patients with Waldenström's macroglobulinemia.

Administration, Oral↗

Magnetic resonance imaging patterns in patients with multiple myeloma.

Sixty-one consecutive patients with multiple myeloma were studied with magnetic resonance (MR) imaging of the spine. Sagittal T1-weighted and short inversion time (TI) inversion recovery (STIR) images were obtained. The MR patterns of the bone marrow were classified as diffuse (D) (n=26), nodular (N) (n=11), D+N (n=13) or normal (n) (n=11). Abnormal patterns were seen in 50 (82%) of the 61 patients. Correlations were found between the MR imaging patterns and some laboratory findings (WBC, haematocrit, platelet count, serum albumin, and percentage of marrow plasmacytosis). The survival of the patients with abnormal MRI patterns was significantly poorer than that of the patients with normal patterns. However, the survival of patients with a nodular pattern did not differ from those with a normal pattern. The MR imaging pattern of the bone marrow in patients with multiple myeloma is a useful factor in the assessment of prognosis.

Adult↗

Bone marrow patterns in patients with aplastic anaemia and myelodysplastic syndrome: observations with magnetic resonance imaging.

Bone marrow magnetic resonance imaging (MRI) was obtained in 48 patients with myelodysplastic syndrome (MDS) (35 cases) or aplastic anaemia (AA) (13 cases). The lower thoracic and lumbar spine were evaluated on sagittal plane using a 1.5 Tesla superconducting MR unit with a surface coil. Pulse sequence of STIRs (TR 2000 msec, TI 160 msec, TE 20 msec) were applied. Four distinct patterns of signal intensity (SI) on the STIR images were classified as follows: pattern 1, homogeneously low SI; 2, marginally high SI; 3, heterogeneously high SI; 4, homogeneously high SI. In all 13 patients with AA, STIR images initially revealed pattern 1. In 25 of 35 cases with MDS patients, the STIR images were initially classified as pattern 3. The STIR images of 6 AA and 5 MDS patients with a clinical response to treatment showed pattern 2 similar to that of normal marrow distribution. The STIR images of MDS patients showed an abnormal distribution of SI. Significant signal changes in the STIR images can be observed in successive examinations of the patients, thus facilitating follow-up of the disease and treatment. MRI of the bone marrow provides a noninvasive means of grossly examining a large fraction and is a useful technique in patients with aplastic anaemia or myelodysplastic syndrome.

Adolescent↗