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1.
J Neurol Sci ; 399: 169-171, 2019 Apr 15.
Article in English | MEDLINE | ID: mdl-30822604

ABSTRACT

Cladophialophora bantiana (C. bantiana) is a life-threatening melanized mycelial fungus causing brain abscess. C. bantiana is usually observed in tropical countries, including India. We report a Japanese case of C. bantiana presenting with myelitis mimicking neuromyelitis optica (NMO) and brain abscess. A 73-year-old man was administered prednisolone (30 mg/day) for antineutrophil cytoplasmic antibody (ANCA)-related vasculitis 100 days before admission. He had right side-dominant paraplegia and sensory loss in the right leg. T2-weighted spinal cord MRI revealed longitudinal high-intensity signals at the T7 to T12 levels. A ring-enhancing lesion at the T10 level was detected on gadolinium (Gd)-enhanced MRI. He was tentatively diagnosed with NMO, and steroid pulse therapy was performed. One month later, an abscess at the right cerebropontine angle was noted on Gd-enhanced brain MRI. Two months later, several subcutaneous intramuscular tumors were detected. Based on the morphological study of the cultured organelle obtained by tumor enucleation and the internal transcribed spacer sequence of ribosomal RNA, the pathogen was identified as C. bantiana. Although he received liposomal amphotericin B treatment, the patient died of respiratory insufficiency. C. bantiana infection should be considered in patients with myelitis presenting with longitudinal lesions and CNS abscess in an immunocompromised state.


Subject(s)
Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Ascomycota , Brain Abscess/diagnosis , Mycoses/diagnosis , Neuromyelitis Optica/diagnosis , Aged , Brain Abscess/drug therapy , Brain Abscess/microbiology , Diagnosis, Differential , Fatal Outcome , Humans , Male , Mycoses/drug therapy , Mycoses/microbiology
2.
Medicine (Baltimore) ; 97(44): e12981, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30383650

ABSTRACT

Disseminated intravascular coagulation (DIC) is a life-threatening condition that frequently occurs in patients with hematologic malignancies. Currently, recombinant human soluble thrombomodulin (rTM) is a therapeutic DIC drug that is manufactured and sold in Japan only. We evaluated the efficacy of rTM compared to that of gabexate mesilate (GM), which was previously used routinely for treating DIC in Japan, in patients with acute myeloid leukemia (AML). This retrospective study enrolled 43 AML patients, including 17 with acute promyelocytic leukemia (APL), that was complicated with DIC. DIC resolution rates in non-APL AML and rTM-treated APL patients were 68.4% and 81.8%, respectively. In non-APL AML patients, the duration of rTM administration was significantly shorter than that of GM (7 vs 11 days), suggesting that rTM could improve DIC earlier than GM, although rTM was used in patients with more severe DIC. Moreover, treatment with rTM significantly improved DIC score, fibrinogen, fibrin/fibrinogen degradation product (FDP), and prothrombin time (PT) ratio. Conversely, treatment with GM only improved the DIC score and FDP. In APL patients, the duration of rTM administration was also significantly shorter than that of GM. No severe side effects associated with the progression of bleeding were observed during rTM administration. These findings suggest that rTM is safe, and its anti-DIC effects are more prompt than GM for treating AML patients with DIC.


Subject(s)
Disseminated Intravascular Coagulation/drug therapy , Gabexate/therapeutic use , Leukemia, Myeloid, Acute/complications , Thrombomodulin/therapeutic use , Adolescent , Aged , Aged, 80 and over , Disseminated Intravascular Coagulation/etiology , Female , Fibrin Fibrinogen Degradation Products , Fibrinogen , Humans , Male , Middle Aged , Prothrombin Time , Recombinant Proteins/therapeutic use , Retrospective Studies , Treatment Outcome , Young Adult
3.
Gan To Kagaku Ryoho ; 45(1): 45-50, 2018 Jan.
Article in Japanese | MEDLINE | ID: mdl-29362306

ABSTRACT

Chemotherapy-induced nausea and vomiting(CINV)were prospectively evaluated using MASCC Antiemesis Tool(MAT) in patients with hematological malignancies in our institution. A total of 33 patients receiving 46 chemotherapy courses were evaluated. Although vomiting was not observed in the acute phase, nausea was seen in 22.6% and 32.3% of the patients in the acute and delayed phases, respectively. Thirty percent(25 cases)of the patients receiving highly emetogenic chemotherapy presented nausea in both the phases, while 40%(18 cases)of the patients receiving moderately emetogenic chemotherapy presented nausea in the delayed phase. The oral intake was quantitated retrospectively in 31 patients with non- Hodgkin's lymphoma, who were hospitalized and received CHOP±R. Prior to the initiation of the chemotherapy, 13 patients received the first generation 5-HT3 receptor antagonist granisetron, while 18 patients received the second generation palonosetron. Oral intake was greater in the patients who were administered palonosetron. Thus, the present study suggested that antiemetic treatment could be improved at our institution.


Subject(s)
Antiemetics/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Non-Hodgkin/drug therapy , Nausea/chemically induced , Vomiting/chemically induced , Adolescent , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Female , Humans , Male , Middle Aged , Prednisolone/administration & dosage , Prednisolone/adverse effects , Retrospective Studies , Rituximab/administration & dosage , Rituximab/adverse effects , Vincristine/administration & dosage , Vincristine/adverse effects , Young Adult
4.
Curr Probl Cancer ; 41(6): 419-425, 2017.
Article in English | MEDLINE | ID: mdl-29061362

ABSTRACT

The objective of this study was to evaluate whether aprepitant in addition to 5-HT3 receptor antagonist is useful for preventing chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients receiving CHOP therapy, and to evaluate the relationship between in vivo kinetics of plasma substance P and these adverse events. Patients with malignant lymphoma who received CHOP chemotherapy or THP (THP-ADR)-COP therapy were investigated for CINV and anorexia for 5 days after the start of chemotherapy. With the first course of chemotherapy, all patients received only granisetron on day1 as an antiemetic. Patients who experienced nausea, vomiting, or anorexia exceeding grade 1 in the first course received aprepitant for 3 days in addition to granisetron with the second course of CHOP chemotherapy. Plasma substance P concentrations at 24 and 72 hours after chemotherapy were measured. Nineteen patients were evaluated. Nausea, vomiting, or anorexia was observed with the first course in 7 of 19 patients. During the second course with aprepitant, no patients experienced vomiting, and the toxicity grade of nausea, vomiting, or anorexia was decreased compared with those in the first course. Substance P concentrations showed no differences after chemotherapy, in patients with nausea, vomiting, or anorexia and in patients without. The addition of aprepitant to 5-HT3 receptor antagonist appears effective for CINV or anorexia for patients who received CHOP chemotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Lymphoma/drug therapy , Morpholines/therapeutic use , Neurokinin-1 Receptor Antagonists/therapeutic use , Serotonin 5-HT3 Receptor Antagonists/therapeutic use , Adult , Aged , Anorexia/blood , Anorexia/chemically induced , Anorexia/drug therapy , Antiemetics/therapeutic use , Aprepitant , Cyclophosphamide/adverse effects , Doxorubicin/adverse effects , Female , Granisetron/therapeutic use , Humans , Lymphoma/blood , Male , Middle Aged , Nausea/blood , Nausea/chemically induced , Nausea/drug therapy , Prednisone/adverse effects , Receptors, Neurokinin-1/metabolism , Substance P/blood , Substance P/metabolism , Vincristine/adverse effects , Vomiting/blood , Vomiting/chemically induced , Vomiting/drug therapy
5.
Intern Med ; 56(18): 2407-2413, 2017 Sep 15.
Article in English | MEDLINE | ID: mdl-28824057

ABSTRACT

Objective We retrospectively compared the clinical efficacy and toxicity of rituximab (R)-THP-COP (pirarubicin, cyclophosphamide, vincristine, and prednisolone) with that of R-CHOP (rituximab, adriamicin, cyclophosphamide, vincristine, and prednisolone) in previously untreated old patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods Patients admitted to our institution between 2004 and 2013 were examined. The patients received either R (375 mg/m2, day 1)-THP-COP (pirarubicin 50 mg/m2 day 1, cyclophosphamide 750 mg/m2 day 1, vincristine 1.4 mg/m2 day 1, and prednisolone 100 mg day 1-5) or R-CHOP (adriamicin 50 mg/m2 day 1, cyclophosphamide 750 mg/m2 day 1, vincristine 1.4 mg/m2 day 1, and prednisolone 100 mg day 1-5). The doses of chemotherapeutic agents were adjusted depending on the patient's age and associated complications. The treatment was performed for 6 to 8 cycles. Results Among 74 patients with DLBCL (median 76, range 65-90 years; male 39, female 35), 29 received R-THP-COP, while 45 received R-CHOP. The overall response rates were 94.6% (complete response 86.4%, partial response 8.1%). The 2-year overall and progression-free survival rates were 77.6% and 68.5% for the R-THP-COP regimen and 79.2% and 78.9% for R-CHOP, respectively. No significant differences were found between these two regimens regarding the clinical efficacies. The most frequent adverse event was neutropenia (72.4% for the R-THP-COP regimen, 88.9% for the R-CHOP regimen). The cardiac function as evaluated by ejection fraction values was not impaired in either regimen. Conclusion R-THP-COP was effective and safe as an alternative to R-CHOP.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cyclophosphamide/therapeutic use , Disease-Free Survival , Doxorubicin/analogs & derivatives , Doxorubicin/therapeutic use , Drug Administration Schedule , Female , Humans , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Neutropenia/chemically induced , Prednisolone/therapeutic use , Prednisone/therapeutic use , Remission Induction , Retrospective Studies , Rituximab/therapeutic use , Treatment Outcome , Vincristine/therapeutic use
6.
Rinsho Ketsueki ; 58(5): 433-437, 2017.
Article in Japanese | MEDLINE | ID: mdl-28592755

ABSTRACT

A 64-year-old man was diagnosed with acute myeloid leukemia M2 (FLT3-ITD-positive). After induction chemotherapy and four courses of consolidation therapy, he underwent umbilical cord blood transplantation (CBT) in his first remission. He developed acute graft-versus-host disease (skin stage 2) after successful engraftment. On post-transplantation day 147, he was admitted to the hospital suffering from pneumonia. During the treatment, drastic thrombocytopenia was observed on day 251. Both platelet-associated immunoglobulin G and platelet antibody producing B cells were detected, and he was diagnosed with immune thrombocytopenia (ITP). Treatment with prednisolone (1 mg/kg/day), eltrombopag (25 mg/day), and intravenous immunoglobulin (400 mg/kg) was commenced, but there was no improvement in his platelet count. After switching from eltrombopag to romiplostim (350 µg/week), and addition of cyclosporine, the platelet count rapidly elevated to 150,000/µl. ITP after allogenic stem cell transplantation is a rare complication, and it is often refractory to the 1st-line treatment such as steroids. Herein, we report successful treatment using a combination of romiplostim and an immunosuppressive agent in the case of treatment failure in ITP that developed after CBT.


Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia, Myeloid, Acute/therapy , Purpura, Thrombocytopenic, Idiopathic/etiology , Fetal Blood , Humans , Male , Middle Aged , Purpura, Thrombocytopenic, Idiopathic/therapy
7.
Rinsho Ketsueki ; 58(12): 2406-2410, 2017.
Article in Japanese | MEDLINE | ID: mdl-29332875

ABSTRACT

A 68-year-old male patient, who was diagnosed with MGUS (IgG-λ) 11 years ago, was referred to our hospital because of a progressing pancytopenia. He was diagnosed with multiple myeloma (MM) and was hospitalized because of fever and pneumonia. Although empiric antibiotic and antifungal therapies were promptly initiated, his pneumonia worsened. Chest CT images revealed diffuse interstitial pneumonia. Although bortezomib/dexamethasone therapy was initiated as a treatment for MM and pneumonia, he showed little response. His pneumonia worsened and progressed to acute respiratory distress syndrome. Using mPSL (500 mg/day), sivelestat, and MM treatment switching to lenalidomide/dexamethasone (Rd), his respiratory status and CT findings rapidly improved. He received Rd therapy as an outpatient; however, after the completion of six cycles of therapy, his MM progressed, with a recurrence of pneumonia and high fever again. The onset of pneumonia was closely associated with MM progression. His pneumonia improved by treatment with mPSL half-pulse and MM treatment switching to carfilzomib/Rd. In the present study, we report the case of a patient with myeloma, who presented with multiple interstitial pneumonia, resulting in respiratory failure twice in concordance with myeloma progression.


Subject(s)
Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/etiology , Multiple Myeloma , Aged , Humans , Lenalidomide , Lung Diseases, Interstitial/drug therapy , Male , Multiple Myeloma/diagnostic imaging , Multiple Myeloma/drug therapy , Recurrence , Thalidomide/analogs & derivatives , Thalidomide/therapeutic use , Treatment Outcome
8.
Anticancer Res ; 36(12): 6655-6662, 2016 12.
Article in English | MEDLINE | ID: mdl-27919998

ABSTRACT

BACKGROUND/AIM: Tumor lysis syndrome (TLS) is a life-threatening complication associated with cancer chemotherapy. We retrospectively evaluated the risk of developing TLS in patients with symptomatic multiple myeloma undergoing chemotherapy. PATIENTS AND METHODS: Sixty-four patients (median age=71 years, range=48-87 years, 35 males/29 females) who were treated at our Institution between April 2006 and December 2015 were evaluated. RESULTS: A total of 124 chemotherapy courses were administered, of which 63 courses were bortezomib-based regimens and 34 courses were immunomodulatory drug (IMiD)-based regimens. TLS occurred in 13 (10.5%) out of 124 chemotherapy courses with five (4.0%) cases of laboratory TLS and eight (6.5%) cases of clinical TLS. The incidences of TLS were 17.5% for bortezomib-containing regimens and 3.2% for non-bortezomib-based regimens. No TLS occurred in the patients treated with IMiD-containing regimens. TLS occurred more frequently in the patients with elevated uric acid, creatinine, or beta-2-microglobulin levels at baseline. The patients with disease classified as advanced International Staging System also developed TLS more frequently. All the patients who developed clinical TLS received bortezomib-containing regimens (8/63, 12.7%). Among them, patients with elevated values of uric acid or creatinine developed clinical TLS more often than those without such elevation. The incidence of clinical TLS was 33.3% if the patients had renal dysfunction at baseline and were subsequently treated with bortezomib-based regimens (8/24 cases). CONCLUSION: Patients with renal dysfunction or a high uric acid level receiving bortezomib-based chemotherapy have a high risk of developing TLS.


Subject(s)
Bortezomib/therapeutic use , Kidney Diseases/drug therapy , Multiple Myeloma/complications , Tumor Lysis Syndrome/etiology , Aged , Aged, 80 and over , Female , Humans , Kidney Diseases/physiopathology , Male , Middle Aged
9.
Oncol Lett ; 9(5): 2119-2125, 2015 May.
Article in English | MEDLINE | ID: mdl-26137024

ABSTRACT

In the present study, the dosage and duration of rasburicase administration were retrospectively evaluated for the ability to control the serum uric acid (S-UA) level in 13 patients diagnosed with hematological malignancies and tumor lysis syndrome (TLS), or those at risk of developing TLS, at the University of Fukui Hospital. At the time of diagnosis, seven patients already exhibited laboratory TLS, and three demonstrated clinical TLS. All patients received rasburicase in addition to chemotherapy agents. The median dose was 0.19 mg/kg (range, 0.13-0.25 mg/kg), and the median duration was four days (range, 1-7 days). Six patients sequentially received a xanthine oxidase inhibitor, allopurinol or febuxostat. The primary estimate was the normalization of the S-UA level at the end of rasburicase treatment and on treatment day seven. The average S-UA level prior to treatment was 10.4±4.5 mg/dl (mean ±standard deviation), and 11 out of 13 patients demonstrated a S-UA level >7 mg/dl. The S-UA level at the end of rasburicase administration was 0.5±1.5 mg/dl and the S-UA level at day seven was 1.4±1.5 mg/dl. All the patients achieved normalization of the S-UA level. On day seven subsequent to the initiation of treatment, the patients receiving rasburicase for a maximum of three days exhibited an S-UA level of 1.9±1.8 mg/dl, while the patients receiving rasburicase for longer than three days demonstrated an S-UA level of 1.0±1.3 mg/dl (P=0.20; Mann-Whitney test). The administration of 0.13 mg/kg and 0.22 mg/kg resulted in comparable UA level reductions. The administration of allopurinol or febuxostat following rasburicase administration suppressed the re-increase in S-UA level. Therefore, it was concluded that reduced administration of rasburicase successfully controlled the S-UA level in TLS.

10.
Oncol Lett ; 9(2): 851-856, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25621059

ABSTRACT

The primary objective of the present study was to correlate blood cell counts (lymphocyte, monocyte and platelet counts) with early disease relapse following the attainment of complete remission (CR) by the rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP)-like regimen in patients with advanced diffuse large B-cell lymphoma (DLBCL). In total, 30 patients were evaluated, with a median follow-up period of 43 months. All the participating patients attained CR. In total, eight patients experienced relapse within two years of the diagnosis, and the three-year overall survival rate was recorded as 77%. The peripheral counts for lymphocytes, monocytes and platelets, and the lymphocyte-monocyte ratio, all of which have been reported to be prognostic in DLBCL, were assessed. None of these parameters were correlated with the incidence of early relapse or with the prognosis. The lymphocyte count was higher in the patients with durable remission than in those who relapsed, however, no significant differences were identified. Thus, the present study concluded that early disease relapse was not predicted by peripheral blood cell counts in advanced DLBCL that reached CR using the R-CHOP-like regimen.

11.
J Spinal Cord Med ; 38(5): 641-4, 2015 Sep.
Article in English | MEDLINE | ID: mdl-24974738

ABSTRACT

BACKGROUND: Spontaneous spinal epidural hematoma (SSEH) is relatively rare. SSEH with anticoagulants including warfarin and rivaroxaban (Factor Xa inhibitor) have been reported; however, SSEH with Factor X deficiency has not been described yet. METHODS: Case report. FINDINGS: An 82-year-old woman with acquired Factor X deficiency complained of sudden onset of severe posterior neck pain. Magnetic resonance imaging demonstrated an epidural hematoma from C3 to T3 levels. Because she showed tetraparesis on the third hospital day, we performed surgery. Just before surgery, her prothrombin time-international normalized ratio was 2.49, which was immediately reversed by infusion of prothrombin complex concentrate. The patient safely underwent an emergency laminectomy from C3 to T2, in which the epidural hematoma was evacuated. Post-operatively, the patient recovered completely without rebleeding. Hematologists found acquired deficiency of Factor X in this patient with systemic amyloid light-chain amyloidosis. CONCLUSION: To our knowledge, this is the first report of a case of SSEH with Factor X deficiency. A blood coagulation disorder should be considered in patients with SSEH.


Subject(s)
Amyloidosis/complications , Factor X Deficiency/complications , Hematoma, Epidural, Spinal/etiology , Aged, 80 and over , Factor X Deficiency/etiology , Female , Hematoma, Epidural, Spinal/surgery , Humans
12.
Anticancer Res ; 34(12): 7287-96, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25503162

ABSTRACT

BACKGROUND/AIM: Tumor lysis syndrome (TLS) is a life-threatening oncological emergency, and control of serum uric acid level (S-UA) is most important. In this single-institution, short-term and pilot prospective study, the efficacy of a new xanthine oxidase inhibitor, febuxostat, as an alternative to conventional allopurinol, including its effects on hypoxanthine and xanthine, was evaluated in 10 consecutive patients with hematological malignancies at intermediate risk for TLS. PATIENTS AND METHODS: Febuxostat at 40 mg (n=7) or 60 mg (n=3) daily was administered according to renal function, and induction chemotherapy was started within 24 h. The primary end-point was the reduction of S-UA to ≤ 7.5 mg/dl by day 5. RESULTS: The median S-UA at base-line was 8.0 mg/dl (range=3.2-10.6 mg/dl). The median S-UA on day 5 after chemotherapy was 3.3 mg/dl (range=1.1-5.8 mg/dl) (p<0.0001, by paired t-test), indicating successful control of S-UA during chemotherapy. All patients achieved S-UA ≤ 7.5 mg/dl. A simultaneous decrease in serum creatinine and increase in estimated glomerular filtration rate were seen. Serum hypoxanthine and xanthine levels (as the consequence of inhibition of xanthine oxidase) were elevated along with the decrease in S-UA. Xanthine level was elevated higher compared to hypoxanthine level and reached the level reported to cause xanthine nephropathy, but no advance of renal impairment was observed. Serum febuxostat concentrations at 2 h after administration were 891.8 ± 285.0 ng/ml (mean ± SE) for the 40-mg dose and 770.6 ± 242.7 ng/ml for the 60-mg dose (p=0.80, unpaired t-test), showing no accumulation in patients with renal impairment. No febuxostat-related adverse reactions were noted. No patients experienced progressive TLS. CONCLUSION: Febuxostat is promising for the management of TLS of an intermediate-risk patient and further observation and reevaluation regarding xanthine nephropathy should be performed.


Subject(s)
Enzyme Inhibitors/pharmacokinetics , Hematologic Neoplasms/drug therapy , Thiazoles/pharmacokinetics , Tumor Lysis Syndrome/prevention & control , Uric Acid/blood , Xanthine Oxidase/antagonists & inhibitors , Aged , Allopurinol/therapeutic use , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Creatinine/blood , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/adverse effects , Febuxostat , Female , Glomerular Filtration Rate/drug effects , Humans , Hypoxanthine/blood , Male , Middle Aged , Pilot Projects , Prospective Studies , Thiazoles/administration & dosage , Tumor Lysis Syndrome/drug therapy , Xanthine/blood
13.
Anticancer Res ; 34(10): 5631-6, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25275066

ABSTRACT

BACKGROUND/AIM: The prognosis of acute myeloid leukemia (AML) in elderly patients remains poor due to their poor general condition and the intrinsic chemotherapy-resistant nature of their leukemia cells. The present retrospective study evaluated the clinical background as well as the response to treatment, of an unselected group of elderly patients with AML who were admitted to our Institution over a period of six years. PATIENTS AND METHODS: Patients aged 65 years or older with AML admitted to our Institution between January 2005 and May 2011 were evaluated retrospectively. RESULTS: Forty-six patients were admitted to our Institution, among whom 41 received remission induction chemotherapy. Twenty-four patients received intensive chemotherapy, while 13 received low-dose cytarabine-based chemotherapy. Other modalities were used in four patients. Complete remission was obtained in 20 patients (48.8%). The complete remission rate (50.0%) tended to be higher in patients receiving intensive chemotherapy than in those receiving low-dose cytarabine-based regimens (30.7%; p=0.25). The median survival time for the whole patient group was 12 months and the 2-year overall survival was 18%. The median survival times for patients with complete remission and for non-responding patients were 14 months and 7 months, respectively. The 2-year overall survival in patients with complete remission was 32%, while that of non-responding patients was 6% (p=0.0025, log-rank test). CONCLUSION: The present study suggests the necessity of achieving complete remission for obtaining better survival for elderly patients with AML.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Age Factors , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Female , Follow-Up Studies , Humans , Induction Chemotherapy , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/mortality , Male , Treatment Outcome
14.
J Clin Microbiol ; 52(6): 1938-46, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24671792

ABSTRACT

Tetracyclines are administered to cure Japanese spotted fever (JSF) and tsutsugamushi disease (TD). It is generally said that the clinical course of JSF is worse than that of TD despite antibiotic treatment. The precise mechanism underlying the more severe clinical course of JSF is not fully understood. We therefore examined whether the differential cytokine profile between these two infectious diseases contributes to the difference in clinical severity. The serum concentrations of various cytokines (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], and gamma interferon [IFN-γ]) and chemokines (IL-8, interferon-inducible protein 10 [IP-10], monocyte chemoattractant protein 1 [MCP-1], macrophage inflammatory protein 1α [MIP-1α], MIP-1ß, and eotaxin) were measured in 32 TD and 21 JSF patients. The results showed that serum levels of TNF-α in the acute phases of TD and JSF were significantly increased, with a higher concentration of TNF-α in patients with JSF (mean, 39.9 pg/ml) than in those with TD (mean, 13.8 pg/ml). Comparatively higher levels of other cytokines and chemokines (IL-6, IFN-γ, IL-8, IP-10, MCP-1, MIP-1α, and MIP-1ß) were also observed in the acute phase of JSF. The clinical severity score (3.67 ± 1.71) of JSF patients was higher than that of TD patients (1.47 ± 0.77). Our findings revealed that the cytokine and chemokine levels in the acute phase of JSF were significantly higher than those in the acute phase of TD. The differential cytokine levels may be related to the difference in clinical severity between JSF and TD.


Subject(s)
Cytokines/blood , Rickettsia Infections/pathology , Scrub Typhus/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prospective Studies , Severity of Illness Index , Young Adult
15.
Anticancer Res ; 33(9): 3947-51, 2013 Sep.
Article in English | MEDLINE | ID: mdl-24023333

ABSTRACT

Uric acid in serum (S-UA) is produced by the breakdown of the cellular nucleic acids of leukemia cells, and may be a marker of disease aggressiveness. S-UA levels were examined for association with clinical outcomes in patients with acute myeloid leukemia (AML). Fifty-six patients with AML admitted to our Institution were evaluated retrospectively. The median S-UA level at diagnosis was 5.0 mg/dl (range 2-13.8 mg/dl). The S-UA levels did not correlate with peripheral lactate dehydrogenase, peripheral white blood cell counts, or peripheral blast counts, and were not proportional to bone marrow blast counts or marrow cellularity. The S-UA levels in the patients who achieved complete remission were slightly lower than those in those who did not. S-UA levels less than, or equal to the median (5.0 mg/dl) were significantly associated with better prognoses, compared with S-UA levels greater than 5.0 mg/dl. Thus, the S-UA level may predict the prognosis of AML, and is a versatile and cost-effective test for such a purpose.


Subject(s)
Biomarkers, Tumor/blood , Leukemia, Myeloid, Acute/physiopathology , Uric Acid/blood , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , L-Lactate Dehydrogenase/blood , Leukemia, Myeloid, Acute/blood , Male , Middle Aged , Prognosis , Retrospective Studies
16.
Anticancer Res ; 33(8): 3335-40, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23898100

ABSTRACT

BACKGROUND/AIM: The present retrospective study was conducted to measure Wilms' tumor-1 (WT1) mRNA levels in the peripheral blood of patients with acute myeloid leukemia (AML) in order to examine any association with the clinical outcomes. PATIENTS AND METHODS: A total of 58 AML patients were evaluated retrospectively in our institution. WT1 transcripts were determined by real-time reverse transcriptase-polymerase chain reaction in peripheral blood samples. RESULTS: WT1 levels at diagnosis did not vary according to response of induction treatments, and the levels were comparable between the patients with durable remission and the patients with relapse of disease. WT1 levels at the completion of the treatment were higher in the group with relapse of disease than in the group with sustained remission. Detectable WT1 transcripts after the completion of chemotherapy courses were associated with poor prognoses. CONCLUSION: WT1 mRNA levels at treatment completion may predict for prognosis of AML.


Subject(s)
Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Transcription, Genetic , WT1 Proteins/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Female , Gene Expression Regulation, Leukemic , Humans , Leukemia, Myeloid, Acute/blood , Leukemia, Myeloid, Acute/diagnosis , Leukocyte Count , Male , Middle Aged , Prognosis , RNA, Messenger/genetics , RNA, Messenger/metabolism , Survival Analysis , Time Factors , Treatment Outcome , WT1 Proteins/metabolism , Young Adult
17.
Transl Res ; 161(2): 99-109, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23108365

ABSTRACT

Minocycline, which is a member of the broad-spectrum bacteriostatic tetracycline antibiotics group, has also recently been shown to have additional effects that are separate from their antimicrobial function; however, the detailed mechanisms involved remain unknown. We examined the effects of minocycline on cytokine and chemokine production and the expression levels of intracellular phosphorylated proteins in a lipopolysaccharide (LPS)-induced cytokine response model in vitro. In the present study, 3 cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-6, and interferon [IFN]-γ) and 7 chemokines (IL-8, interferon inducible protein [IP]-10, monocyte chemoattractant protein [MCP]-1, macrophage inflammatory protein [MIP]-1α, MIP-1ß, regulated upon activation normal T-cell expressed secreted [RANTES], and eotaxin) were suppressed by minocycline in a dose-dependent manner. Moreover, the phosphorylation of inhibitor of nuclear factor-κB alpha (IκBα) and IκB kinase (IKK)α/ß, which is located upstream from IκBα, was significantly suppressed by minocycline, whereas the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK), p38, and TGF-ß-activated kinase (TAK)1 were not affected. Thus, minocycline appears to inhibit the signaling pathway at the level of IKKα/ß phosphorylation. In conclusion, minocycline was found to reduce the production of multiple cytokines and chemokines by inhibiting LPS-induced IKKα/ß phosphorylation. That is, minocycline appears to be a potent inhibitor of IKKα/ß phosphorylation. From a clinical and translational significance point-of view, these findings suggest that the use of minocycline offers the advantage of providing both antimicrobial and anti-inflammatory effects, which may be key in treating certain types of infectious diseases, particularly those that lead to hypercytokinemia and chronic inflammatory disorders.


Subject(s)
Anti-Bacterial Agents/pharmacology , Chemokines/metabolism , I-kappa B Kinase/metabolism , Minocycline/pharmacology , Monocytes/drug effects , Cell Line, Tumor , Humans , I-kappa B Kinase/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Monocytes/enzymology , Phosphorylation
18.
Int J Infect Dis ; 17(4): e271-6, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23228627

ABSTRACT

OBJECTIVES: The rapid diagnosis of bacteremia is crucial for patient management including the choice of antimicrobial therapy, especially in cases of hematological disease, because neutropenia occurs frequently during antineoplastic chemotherapy or disease progression. We describe a rapid detection and identification system that uses universal PCR primers to amplify a variable region of bacterial 16S ribosomal DNA (rDNA), followed by DNA microarray hybridization. METHODS: Probes for 72 microorganisms including most causal clinical pathogens were spotted onto a microarray plate. The DNA microarray and conventional methods of identification were applied to 335 cultures from patients with hematological diseases. RESULTS: Forty-one samples (12.2%) tested positive by conventional blood culture test in a few days, while 40 cases (11.9%) were identified by the new method within 24 h. The sensitivity and specificity of this new method were 93% and 99%, respectively, compared with conventional blood culture testing. CONCLUSIONS: PCR combined with a DNA microarray is useful for the management of febrile patients with hematological diseases.


Subject(s)
Bacteremia/diagnosis , DNA, Bacterial/analysis , DNA, Ribosomal/genetics , Hematologic Diseases/diagnosis , Oligonucleotide Array Sequence Analysis/methods , Polymerase Chain Reaction/methods , RNA, Ribosomal, 16S/genetics , Bacteremia/genetics , Bacteremia/microbiology , DNA Primers , Gene Amplification , Hematologic Diseases/genetics , Hematologic Diseases/microbiology , Humans , Nucleic Acid Hybridization , Sensitivity and Specificity
19.
Anticancer Res ; 32(11): 5051-7, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23155278

ABSTRACT

The clinical significance of serum soluble interleukin-2 receptor (sIL2R) levels was retrospectively assessed in patients with advanced diffuse large B-cell lymphoma (DLBCL). Twenty-one patients, who were newly-diagnosed with advanced DLBCL (stage III and IV) between 2006 and 2009, were evaluated. The median follow-up period was 37 months. All patients received 6-8 cycles of chemotherapy with rituximab in combination with doxorubicin, cyclophosphamide, vincristine, and prednisolone (CHOP)-like regimens and attained complete remission. Although all patients reached complete remission, six patients experienced disease relapse within 1 year after treatment completion. The overall survival was significantly poorer in patients with relapse than in patients with durable remission. The sIL2R levels after the sixth cycle of treatment were significantly higher in the relapse group than in the non-relapse group. Thus, the present study suggests sIL2R levels to be a valuable predictor for the prognosis of patients with advanced DLBCL.


Subject(s)
Biomarkers, Tumor/blood , Lymphoma, Large B-Cell, Diffuse/blood , Neoplasm Recurrence, Local/blood , Receptors, Interleukin-2/blood , Aged , Aged, 80 and over , Antibodies, Monoclonal, Murine-Derived , Antineoplastic Combined Chemotherapy Protocols , Biomarkers, Tumor/analysis , Cyclophosphamide , Doxorubicin , Enzyme-Linked Immunosorbent Assay , Female , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prednisone , Prognosis , Receptors, Interleukin-2/analysis , Retrospective Studies , Rituximab , Vincristine
20.
Am J Med Sci ; 343(5): 419-20, 2012 May.
Article in English | MEDLINE | ID: mdl-22173051

ABSTRACT

A 77-year-old man treated with prednisolone for pemphigus developed severe sepsis by Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. Several antibiotics were administered. A peripheral blood smear showed growth of a large number of yeast extending pseudohyphae which could be seen both inside and outside of leucocytes. Antifungal agents were added immediately; however, he did not recover. Several days later, blood culture showed Candida albicans septicemia. The autopsy revealed microabscesses in the lung, heart, liver and kidney. A large amount of neutrophil invasion and yeast with pseudohyphae were also detected.


Subject(s)
Candidemia/diagnosis , Fungemia/complications , Pemphigus/complications , Pseudomonas Infections/complications , Staphylococcal Skin Infections/complications , Aged , Candidemia/complications , Fatal Outcome , Fungemia/microbiology , Humans , Male , Methicillin-Resistant Staphylococcus aureus , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa , Skin Ulcer/complications , Staphylococcal Skin Infections/microbiology
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