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ABSTRACT: Intravascular large B-cell lymphoma (IVLBCL) is a rare form of non-Hodgkin's lymphoma characterized by a proliferation of tumor cells within the lumina of small to medium-sized vessels. Because there are few or no concomitant solid lesions, a diagnosis of IVLBCL usually cannot be established by CT or MR imaging. Herein, we describe a case of IVLBCL involving the uterus, in which (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) was useful for diagnosis. A 47-year-old woman was referred to our hospital because of fever and anemia. Laboratory examination demonstrated anemia and thrombocytopenia. Bone marrow aspiration and biopsy showed hemophagocytosis without involvement of lymphoma cells. Random skin biopsy did not demonstrate lymphoma involvement. FDG-PET/CT imaging showed FDG accumulation in the uterus. MR imaging demonstrated uterine leiomyoma only. Based on these findings, uterine endometrial biopsy was performed and histological diagnosis of IVLBCL involving the uterus was established. She received 6 courses of R-CHOP therapy and high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation. At present, she remains in complete remission after 33 months.
[Rinshō ketsueki] The Japanese journal of clinical hematology 11/2011; 52(11):1777-81.
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Asia-Pacific Journal of Clinical Oncology 09/2011; 7(3):315-6. · 0.58 Impact Factor
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ABSTRACT: Acute leukemia (AL) is characterized by overgrowth of neoplastic hematopoietic precursor cells in the bone marrow. After successful chemotherapy in patients with AL, the growth of leukemic cell is thought to be replaced by the recovery of normal hematopoietic cells as a consequence of the activity of anti-cancer agents in eradicating all hematopoietic cells, whether or not they are leukemic cells. However, little is known about the effects of anti-cancer agents on marrow stromal cells, which play a crucial role in supporting hematopoietic cell development. In the present study, we investigated the direct activity of cytosine arabinoside (Ara-C), a key drug for treatment of AL, on human non-leukemic marrow stromal cells by analyzing the effect of Ara-C on gene expression.
Stromal cells were established from 11 patients with no neoplastic hematopoietic precursor cells in the bone marrow. The cells were treated with Ara-C for one week, co-cultured with allogeneic CD34-positive cells, and subjected to colony assay to evaluate their supportive function. A genome-wide DNA microarray analysis was performed to determine Ara-C-induced changes in gene expression in the stromal cells.
Treatment of the stromal cells with Ara-C resulted in a dose-dependent increase in their supportive function. These effects were more evident in the late phase than in the early phase of co-culture with CD34-positive cells, suggesting that Ara-C-treated stromal cells preferably support very immature cells, rather than committed progenitor cells. Furthermore, gene expression profiling with DNA microarrays revealed prominent up-regulation of growth-differentiation factor 15 (GDF15), a divergent member of the transforming growth factor beta superfamily, with concomitant down-regulation of colony-stimulating factor 1 receptor (CSF-1R), both of which are predominantly expressed on macrophages.
Our present study demonstrated that Ara-C directly enhanced the ability of stromal cells to support the development of immature hematopoietic cells, possibly by modulating the function of macrophages in the bone marrow microenvironment. This novel action of Ara-C in the marrow microenvironment may contribute to the better understanding and management of chemotherapy for AL.
Osaka city medical journal 12/2010; 56(2):11-20.
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Cancer genetics and cytogenetics 07/2010; 200(1):70-2. · 1.54 Impact Factor
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Yoshiki Terada,
Hirohisa Nakamae,
Ran Aimoto,
Hiroshi Kanashima,
Erina Sakamoto,
Mizuki Aimoto,
Eri Inoue,
Hideo Koh,
Takahiko Nakane,
Yasunobu Takeoka,
Masahiko Ohsawa,
Ki-Ryang Koh,
Takahisa Yamane,
Yoshitaka Nakao, Kensuke Ohta,
Atsuko Mugitani,
Hirofumi Teshima,
Masayuki Hino
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ABSTRACT: Recently, maintaining higher relative dose intensity (RDI) of chemotherapeutic drugs has become a widespread practice in an attempt to achieve better outcomes in the treatment of aggressive lymphoma. The addition of rituximab to chemotherapy regimens has significantly improved outcome in diffuse large B-cell lymphoma (DLBL). However, it is unknown if higher RDI in chemotherapy when combined with rituximab leads to a better outcome in aggressive B-cell lymphoma.
We retrospectively evaluated the impact of the RDI of initial chemotherapy (consisting of cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab (R-CHOP) on outcome in 100 newly diagnosed DLBL patients.
A multivariate Cox regression model showed that RDI trended towards a significant association with mortality [hazard ratio per 0.1 of RDI = 0.8; 95% confidence interval 0.6-1.0; P = 0.08]. Additionally, on multivariate logistic analysis, advanced age was a significant factor for reduced RDI.
Our data suggest that in DLBL patients, mortality was affected by RDI of R-CHOP as the initial treatment, and the retention of a high RDI could therefore be crucial.
Journal of Experimental & Clinical Cancer Research 09/2009; 28:116. · 2.15 Impact Factor
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International journal of hematology 07/2009; 90(1):11-2. · 1.17 Impact Factor
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Tomofumi Takaya,
Yoshio Takeuchi,
Hideto Nakajima,
Saori Nishiki-Kosaka,
Katsuya Hata,
Yoichi Kijima,
Tomoyuki Kita,
Mitsuaki Ito,
Masashi Okamoto,
Yuji Nishikawa,
Toshihiko Seo,
Rie Takaoka, Kensuke Ohta,
Keiko Yodoi,
Seinosuke Kawashima
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ABSTRACT: A 53-year-old man, who had been treated for penile origin diffuse large B cell type non-Hodgkin lymphoma (NHL), suffered from right femoral pain and dyspnea. Positron emission tomography (PET) revealed abnormal accumulation in his right femur and cardiac segments. Transthoracic echocardiography revealed massive localized pericardial effusion with the collapse of both ventricles and the mass-like echo in the left atrium. We performed emergent pericardiocentesis and diagnosed this case as a recurrence of NHL with cardiac metastasis. With the use of transesophageal echocardiography (TEE), we confirmed the mass-like echo around the inter-atrial septum, which directly invaded to the aortic ring and the right atrial wall. In order to evaluate the effect of chemotherapy, we performed TEE and observed the precise changes of intra-cardiac tumor size. With the use of TEE monitoring, we could select the appropriate chemotherapeutic regimen, and the tumor became smaller and finally diminished. The femoral accumulation detected by PET also disappeared. We experienced a case of cardiac metastasis of NHL complicated with left ventricular diastolic collapse due to the massive localized pericardial effusion. TEE is a useful tool to evaluate precisely the efficacy of chemotherapy for intra-cardiac tumors.
Journal of Cardiology 07/2009; 53(3):447-52. · 1.28 Impact Factor
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Kensuke Ohta,
Saori Nishiki Kosaka,
Yoshitaka Nakao,
Takeo Kumura,
Kiyomichi Hagihara,
Erina Sakamoto,
Shuichiro Okamoto,
Asao Hirose,
Yasutaka Aoyama,
Ryousuke Yamamura,
Yoshiki Hayashi,
Yukari Umemoto,
Yoshiki Terada,
Yasunobu Takeoka,
Takahiko Nakane,
Hideo Koh,
Masayuki Hino
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ABSTRACT: Recently, empirical antifungal therapy with intravenous itraconazole (ITCZ) for neutropenic patients with antibiotics-resistant fever has been approved by Japanese Ministry of Health, Labour and Welfare on the bases of previous multicenter trials of foreign countries. In this study, we conducted a single-arm, multicenter, prospective study in order to evaluate the efficacy of empirical ITCZ injection on Japanese patients. Sixty-eight patients with hematological diseases who underwent anticancer chemotherapy or stem cell transplantation were enrolled. In this study, we found that the overall clinical response rate to ITCZ injection was 67.6% and success rate of achieving composite endpoints including survival, defervescence during neutropenia, no breakthrough fungal infections, and no premature discontinuation of drug was 50.0%. Mild adverse reactions were observed in 6 patients (8.8%). Further analysis revealed that possible/probable deep fungal infection according to the 2002 and 2008 criteria defined by EORTC/MSG were found in 19.1 and 7.5% of the patients, respectively. Interestingly, response rate to ITCZ injection of possible/probable cases according to the 2002 and 2008 criteria was 61.5% (8/13) and 100% (5/5), respectively. These results not only proved the good efficacy and safety of empirical ITCZ injection for Japanese patients, but also indicated a utility of the drug on future "presumptive" approach.
International journal of hematology 06/2009; 89(5):649-55. · 1.17 Impact Factor
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ABSTRACT: Mesenchymal stem cells (MSCs) may modulate inflammatory responses resulting in improvement in inflammatory diseases, as well as tissue regeneration via cellular differentiation. We examined the therapeutic effects of exogenously administered MSCs in dextran sulfate sodium (DSS)-induced colitis in rats.
Experimental colitis was produced in inbred male Lewis rats by administration of 4% DSS in drinking water for 7 days. MSCs (5x10(6) cells) which were isolated from whole marrow cells and cultured in an optimal medium for MSC outgrowth were administered to the treated rats via the tail vein on days 0, 2, and 4. On day 7, we evaluated colon length, histological changes, and colonic various mRNA expressions by RT-PCR. Localization of MSCs was evaluated using a green-fluorescent cell linker dye. To evaluate the anti-inflammatory action of MSCs, we assayed LPS-induced TNF-alpha secretion in a co-culture of MSCs and monocytes (THP-1 cells) using ELISA.
MSCs reduced in bloody stools, weight loss, colon shortening, and microscopic injuries. In the rectum of MSCs-treated rats, mRNA expression of TNF-alpha, IL-1beta, and COX-2 decreased to 40, 15, and 15% of their respective control levels. MSCs significantly suppressed mRNA expression of VEGF, HGF, and b-FGF to 40, 25, and 25% of their respective control levels. Green-fluorescent-labeled MSCs were found only within the lamina propria in inflamed regions. LPS-induced TNF-alpha secretion by THP-1 cells was significantly suppressed by co-culture with MSCs dose-dependently.
We conclude that exogenous MSCs accumulated in inflamed tissues and ameliorated DSS-induced colitis via a local anti-inflammatory action.
Life Sciences 11/2008; 83(23-24):771-9. · 2.53 Impact Factor
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Naoto Hirata,
Kazunari Tominaga, Kensuke Ohta,
Kaori Kadouchi,
Hirotoshi Okazaki,
Tetsuya Tanigawa,
Masatsugu Shiba,
Toshio Watanabe,
Yasuhiro Fujiwara,
Shiro Nakamura,
Nobuhide Oshitani,
Kazuhide Higuchi,
Tetsuo Arakawa
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ABSTRACT: A 50-year old woman suffering from diabetes had a CT scan that revealed a diffuse thickening of small intestinal wall and swollen paraaortic lymph nodes. An esophagogastroduodenoscopy (EGD) confirmed multiple polypoid lesions in the duodenum and small intestine, and conventional histological testing revealed non-specific inflammatory changes. Further examinations including the immunohistochemical profiles of the biopsied specimens led us to diagnose the lesion as a marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type, forming multiple lymphomatous polyposis sequentially spreading from duodenal bulb to terminal ileum. According to Lugano's classification, its staging was clinically diagnosed as stage II. Two courses of a standard CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and predonisolone) regimen with rituximab reduced the lesion and the patient had a almost complete response. A 5-year follow-up EGD and histological examinations detected no recurrence of the disease.
World Journal of Gastroenterology 04/2007; 13(9):1453-7. · 2.47 Impact Factor
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Yasunobu Takeoka,
Mika Nakamae,
Hirohisa Nakamae,
Kiyoyuki Hagihara,
Erina Sakamoto,
Takahiko Nakane,
Hideo Koh,
Ki-Ryang Koh, Kensuke Ohta,
Takahisa Yamane,
Masayuki Hino
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ABSTRACT: There have been many reports of patients with ampulla cardiomyopathy described as takotsubo-shaped cardiomyopathy in the cardiovascular field. This unique cardiomyopathy is characterized by transient apical ballooning and hypokinesis of the left ventricle. We describe 2 cases of ampulla cardiomyopathy associated with hemophagocytic lymphohistiocytosis (HLH). In both of the patients, ventricular dysfunction suddenly occurred during the active phase of HLH. In each case, the findings on ECG, echocardiogram and left ventriculogram were compatible with ampulla cardiomyopathy. To our knowledge, this communication is the first to report cases of ampulla cardiomyopathy associated with HLH. Our cases suggest that HLH hypercytokinemia may have a role in causing ampulla cardiomyopathy.
Acta Haematologica 02/2007; 117(4):205-10. · 1.35 Impact Factor
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ABSTRACT: Thrombotic microangiopathy (TMA) impairs long-term survival after allogeneic hematopoietic stem cell transplantation (HSCT). As the allogeneic HSCT procedure has developed, addressing risk factors for TMA has become more complicated. The aim of this study was to investigate the impact of transplant-associated factors on TMA incidence in patients who have undergone HSCT in various settings. One hundred twenty-three consecutive allogeneic HSCT patients with hematologic diseases receiving myeloablative and reduced-intensity conditioning were evaluated retrospectively. Of 123 patients, 22 (17.9%) developed TMA after HSCT. Multivariate analysis showed the significance of GVHD grade II-IV, and the use of FK506 and the use of high-dose busulfan (Bu) (16 mg/kg) persisted. The hazard ratios of the use of FK506, the use of high-dose Bu (16 mg/kg), and GVHD grade II-IV for TMA were 8.7 (95% CI 2.0-37), 5.7 (95% CI 1.5-21), and 3.4 (95% CI 1.3-9.1), respectively. In the present study, reduced-intensity conditioning did not have an advantage over myeloablative conditioning in decreasing the incidence of TMA after HSCT. Our results also showed that high-dose Bu (16 mg/kg) for the conditioning and FK506 for the prophylaxis of GVHD might contribute more significantly to TMA onset after HSCT than other agents.
American Journal of Hematology 08/2006; 81(7):525-31. · 4.67 Impact Factor
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ABSTRACT: Recently, clinical studies of cord blood transplantation (CBT) in adults after myeloablative or nonmyeloablative conditioning regimens showed cord blood (CB) could effectively restore hematopoiesis and was associated with acceptable levels of graft versus host disease (GVHD).
This study reports the results of cord blood transplantation in 7 adults with hematological malignancies.
Median age was 56 years (range, 43-69 years). HLA match was 4 of 6 in 4 cases and 5 of 6 in 3 cases. Median nucleated cell dose was 2.74 x 10(7) cells/kg (range, 2.13-3.80) and CD34+ cell dose was 1.15 x 10(5) cells/kg (range, 0.44-2.79). Three patients had primary graft failure. There was one early death at day 24 after CBT due to pneumonia. Three patients with engraftment are alive and free of disease at day 390, day 348 and day 164 after CBT. Acute GVHD grade II occurred in 2 cases with engraftment, and chronic GVHD occurred in 1 of 3 evaluable patients. Six patients with and without engraftment received more than 2.0 x 10(7) cells/kg nucleated cells. Three patients without engraftment received CD34+ cell dose less than that of 3 patients with engraftment.
It is considered that graft CD34+ cell dose besides nucleated cell dose is important for engraftment. We believe that adult patients without suitable related or unrelated bone marrow donors should be considered as candidates for CBT by the choice of CB including both sufficient nucleated cell dose and CD34+ cell dose.
Osaka city medical journal 01/2006; 51(2):83-8.
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ABSTRACT: There are three distinct types of doxorubicin-induced cardiotoxicity (acute, chronic, and late-onset). Although previous studies with animal models suggest that angiotensin II plays a key role in the process of the doxorubicin-induced cardiotoxicity, there has been no such observation in humans. This randomized study investigated whether valsartan, a new class of angiotensin II receptor blocker (ARB), can inhibit acute cardiotoxicity after doxorubicin-based chemotherapy.
Forty consecutive patients with untreated non-Hodgkin lymphoma who were scheduled to undergo standard chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) (mean age, 56 yrs; range, 24-70 yrs) were randomized with minimization methods to receive CHOP with or without 80 mg/day of valsartan. Acute cardiotoxicity was comprehensively evaluated with neurohumoral, echocardiographic, and electrocardiographic markers before and on Days 3, 5, and 7 after the initiation of CHOP.
CHOP induced transient increases in the left ventricular end-diastolic diameter in an echocardiogram, the QTc interval and QTc dispersion in an electrocardiogram, and in the plasma brain and atrial natriuretic peptides. All these changes returned to nearly normal levels within a week after CHOP (P < 0.001). Notably, valsartan significantly prevented all these changes except for the elevation in atrial natriuretic peptide (P < 0.05). No significant change was observed in blood pressure or heart rate between the valsartan and control groups.
The results indicate that angiotensin II may play an essential role in acute CHOP-induced cardiotoxicity in humans. Future long-term studies are necessary to judge whether ARBs have a potential to prevent the chronic or late-onset types of doxorubicin-induced cardiotoxicity.
Cancer 01/2006; 104(11):2492-8. · 4.77 Impact Factor
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Erina Sakamoto,
Takahisa Yamane,
Takahiko Nakane,
Yasunobu Takeoka,
Asao Hirose,
Kiyoyuki Hagihara,
Hirohisa Nakamae, Kensuke Ohta,
Michihiko Hirayama,
Yoshihiro Ikura,
Masahiko Ohsawa,
Toru Sawada,
Toshiyuki Kitoh,
Masayuki Hino
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ABSTRACT: A 48-year-old man was referred to Sakai Municipal Hospital with nasal discharge and right facial swelling. The pathological findings of a nasal cavity tumor revealed stage IIB NK/T-cell lymphoma. He was admitted to our hospital and received CHOP therapy, resulting in progressive disease. Irradiation therapy combined with DeVIC chemotherapy also could not shrink his lymphoma. Then, two courses of L-asparaginase(L-Asp) were administered, resulting in partial improvement of the nasal and pharynx lesions, resolution of the fever and improvement of his performance status. On the day before a third course of L-Asp, he again developed a lowgrade fever. Although L-Asp was administered for several days, marked elevation of serum LDH, AST, ALT level, and thrombocytopenia persisted, and he died. Post-mortem examinations revealed hemophagocytosis in the bone marrow and liver, and infiltration of lymphoma cells into multiple organs including left lower lung, liver, spleen and kidneys. Although L-Asp was effective against nasal NK/T-cell lymphoma resistant to combination chemotherapy and irradiation therapy, the effectiveness of the single agent with L-Asp was only transient. L-Asp based regimen should be used as first-line therapy if asparagine synthetase protein expression is low using an immunohistochemical method.
Gan to kagaku ryoho. Cancer & chemotherapy 12/2005; 32(12):1993-6.
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Asao Hirose,
Takahisa Yamane,
Yasuhiro Nakajima,
Masahiro Manabe,
Hiroshi Kanashima,
Kiyoyuki Hagihara,
Erina Sakamoto,
Mika Nakamae,
Yoshiki Terada,
Saori Kosaka,
Yasutaka Aoyama,
Chikahiko Sakamoto,
Takeo Kumura,
Ki-Ryang Koh,
Manabu Hirai, Kensuke Ohta,
Yoshitaka Nakao,
Atsuko Mugitani,
Hirohumi Teshima,
Masayuki Hino
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ABSTRACT: To evaluate the results of high-dose chemotherapy (HDT) and autologous hematopoietic stem cell transplantation (ASCT) in patients with diffuse B-cell aggressive non-Hodgkin's lymphoma(NHL). Between 1991 and 2004, 25 patients who did not achieve complete remission and 26 in complete remission from conventional chemotherapy received HDC-ASCT. Of 25 patients with refractory NHL,14 were chemotherapy-sensitive before HDT-ASCT and 11 were chemotherapy-resistant. CR was achieved after HDC-ASCT in 50% of 14 chemotherapy sensitive patients and in none of 11 chemotherapy-resistant patients. The 5-year probability of event-free survival for chemotherapy-sensitive and chemotherapy-resistant patients was 51.3% and 20.8%, respectively (p<0.05, log-rank test). Moreover, the 5-year probability of event-free survival for patients in the low-risk group with International Prognostic Index (IPI) and in the high-risk group with IPI was 75.0% and 16.3%, respectively (p<0.05, log-rank test). HDT-ASCT should be considered for patients with refractory aggressive NHL who are chemotherapy-sensitive rather than chemotherapy-resistant. Twenty-six patients in complete remission received consolidation therapy with HDT-ASCT. The 5-year probability of disease-free survival for patients in the low-risk group and in the high-risk group was 68.8% and 60.0%,respectively (p = 0.9 6). HDT-ASCT should be considered for patients at high risk who achieve complete remission after induction treatment. In future, HDT-ASCT combined with rituximab as induction therapy or as consolidation therapy is needed for patients with aggressive NHL in the high-risk group.
Gan to kagaku ryoho. Cancer & chemotherapy 12/2005; 32(13):2059-64.
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ABSTRACT: In 1975, Dixson reported that anti-platelet IgG on platelets from patients with idiopathic thrombocytopenic purpura (ITP) is greater than in normal people, by determining anti-platelet antibodies directly on the platelet surface with a quantitative complement lysis-inhibition-assay. Since then, platelet-associated IgG (PAIgG) has been thought of as evidence of ITP. Although platelets from ITP patients show significantly higher PAIgG values than from normal control individuals, PAIgG is not specific for autoantibody because it increases in other than immune ITP patients.
We analyzed positive platelet percentage with various platelet-associated immunoglobulins: IgG, IgM, IgA, and total immunoglobulins, in the blood from 17 normal donors and 23 ITP patients.
The specificity for ITP disease was better in flow cytometry than in ELISA, because, other than ITP, only aplastic anemia was positive in flow cytometry; however, various disorders (aplastic anemia, chronic lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome) showed positive in ELISA. Flow cytometry methods had the same sensitivity for ITP disease as ELISA. However, it is supposed that there was no nonimmune ITP in this study because the PAIgG negative patients (n = 1) showed positive results in flow cytometry.
Flow cytometry method was effective for ITP screening, especially for specificity.
Cytometry Part B Clinical Cytometry 12/2005; 68(1):37-42. · 2.53 Impact Factor
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Hirohisa Nakamae,
Kimihide Himuro,
Kiyoyuki Hagihara,
Yoshiki Terada,
Erina Sakamoto,
Yasunobu Takeoka,
Takahiko Nakane,
Mika Nakamae, Kensuke Ohta,
Takahisa Yamane,
Hiroyuki Shimada,
Takami Miki,
Masayuki Hino
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ABSTRACT: A 57-year-old man underwent an autologous hematopoietic stem cell transplant for mantle cell lymphoma in August 1999. Anemia and thrombocytopenia appeared in November 2001. He was diagnosed with further hematological examination as having acute myeloid leukemia with multilineage dysplasia following secondary myelodysplastic syndrome. He received the allogeneic hematopoietic stem cell transplant from his HLA DRB1 locus mismatched brother in May 2002. The nonmyeloablative preparative regimen consisted of fludarabine 30mg/m2 for 6 days and busulfan 4mg/kg for 2 days. Eosinophilia, decrease of lacrimal fluid and liver dysfunction appeared on Day 104. We diagnosed this as chronic GVHD and treated the patient with prednisolone 10 mg/day. Thereafter, his chronic GVHD gradually improved. He had fever and myalgia in the extremities and lumbar region with elevated serum CPK and aldolase in January 2003. Histological examination led to a diagnosis of polymyositis simultaneously with chronic GVHD. Prednisolone 50 mg/day as an initial dose was started for the polymyositis following which the prednisolone dose was gradually tapered off. The polymyositis improved promptly after the administration of prednisolone and remains in remission with a current maintenance program of prednisolone 5 mg/day.
[Rinshō ketsueki] The Japanese journal of clinical hematology 12/2005; 46(11):1213-7.
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ABSTRACT: Patients with hematological malignancies and aplastic anemia become complicated by critical infections, which are one of the common causes of death in many cases. This is a retrospective investigation of the factors that affect the efficacy of antibiotic treatment of febrile neutropenia (FN). The subjects consisted of 98 cases that developed FN during their hospitalization in this department and received antibiotics as a first-line treatment. Parameters evaluated were age, gender, with or without administration of granulocyte-colony stimulating factor (G-CSF), with or without hematopoietic transplantation, the number of antibiotics, the type of antibiotics, the highest level of C-reactive protein (CRP), with or without antifungal prophylaxis, the duration of neutropenia, and the number of neutrophils before and after the administration of antibiotics. Logistic analysis was used for statistical evaluation. With univariate analysis, significant clinical efficacy was observed with the use of carbapenems (p = 0.0009, Odds; 4.58) when the number of neutrophils was not less than 500/microL (P < 0.0001, Odds: 14.1) after administration of antibiotics. Furthermore, even when multivariate analysis was performed, significant clinical efficacy was observed independently in the use of carbapenems (P = 0.02, Odds: 3.73) and when the number of neutrophils was not less than 500/microL (P < 0.0001, Odds: 10.4) after administration of antibiotics. In this investigation, as a first-line treatment of FN, carbapenem antibiotic is recommended as a primary choice, when the number of neutrophils was expected to decrease after administration.
The Japanese journal of antibiotics 09/2005; 58(4):382-7.
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Ryo Matsumoto,
Takashi Omura,
Minoru Yoshiyama,
Tetsuya Hayashi,
Sakiko Inamoto,
Ki-Ryang Koh, Kensuke Ohta,
Yasukatsu Izumi,
Yasuhiro Nakamura,
Kaname Akioka,
Yasushi Kitaura,
Kazuhide Takeuchi,
Junichi Yoshikawa
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ABSTRACT: Vascular endothelial growth factor (VEGF) plays an important role in inducing angiogenesis. Mesenchymal stem cells (MSCs) may have potential for differentiation to several types of cells, including myocytes. We hypothesized that transplantation of VEGF-expressing MSCs could effectively treat acute myocardial infarction (MI) by providing enhanced cardioprotection, followed by angiogenic effects in salvaging ischemic myocardium.
The human VEGF165 gene was transfected to cultured MSCs of Lewis rats using an adenoviral vector. Six million VEGF-transfected and LacZ-transfected MSCs (VEGF group), LacZ-transfected MSCs (control group), or serum-free medium only (medium group) were injected into syngeneic rat hearts 1 hour after left coronary artery occlusion. At 1 week after MI, MSCs were detected by X-gal staining in infarcted region. High expression of VEGF was immunostained in the VEGF group. At 28 days after MI, infarct size, left ventricular dimensions, ejection fraction, E wave/A wave ratio and capillary density of the infarcted region were most improved in the VEGF group, compared with the medium group. Immunohistochemically, alpha-smooth muscle actin-positive cells were most increased in the VEGF group.
This combined strategy of cell transplantation with gene therapy could be a useful therapy for the treatment of acute MI.
Arteriosclerosis Thrombosis and Vascular Biology 07/2005; 25(6):1168-73. · 6.37 Impact Factor
