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Biomedical subjects

M Harada

Publications and source records attributed to M Harada.

At least 325 records · Page 18Linked to original sources

[A giant invasive thymoma made resectable by cisplatin + vincristine + doxorubicin + etoposide (CODE)].

A 39-year-old man experienced cough and dyspnea by right massive pleural effusion. A large tumor was found in the anterior mediastinum and it had invaded the chest wall all around. The diagnosis was invasive thymoma stage IV a by biopsy. His tumor was too large to be resected, so chemotherapy was planned. The tumor responded well to cisplatin + etoposide until day 7, but it relapsed immediately between doses. Hence, we administered cisplatin + vincristine + doxorubicin + etoposide (CODE) with G-CSF for its high-dose intensity. The tumor diminished in size, and the chest wall invasion almost disappeared. An operation was performed. We describe our experience with a case of invasive thymoma which responded to CODE.

Adult↗

[Syphilitic orchitis: a case report].

Syphilitic orchitis is recently a rare disease in Japan. A 75-year-old man was referred to our hospital with the complaint of persistent swelling of the left scrotal contents in spite of prior antibiotic therapy. We suspected a testicular tumor because of lack of pain, and performed high orchiectomy. The specimen showed wide-ranged necrosis with a non-specific inflammatory change of the testis on hematoxylin-eosin stain. After performing analysis using a polymerase chain reaction method, we reached the final diagnosis of syphilitic orchitis.

Aged↗

[A clinical application of laser scanning cytometer--the significance in the cytology as an additional diagnostic technique].

Laser scanning cytometer (LSC) is a new machine similar to flow cytometer but with advantages for certain clinical and research applications. LSC is a microscope based and measures cells on a slide with the position of each cell on the slide. This new technique of LSC can be utilized on extremely small specimens and enables direct correlation of all of the measured fluorescent parameters with light microscopic cytologic morphology. To date, LSC has been successfully used to perform DNA content analysis of numerous specimen types and automated analysis of fluorescence in situ hybridization specimens. In this report, we describe characteristics of LSC comparison with flow cytometry and a clinical application of LSC focused on DNA content analysis in clinical specimens with pulmonary disorders. LSC provides a number of benefits that may make it more suitable for clinical laboratories than FCM.

Bronchi↗

[Antimicrobial activities of beta-lactam antibiotics against clinically isolated Haemophilus influenzae].

Antimicrobial activities of oral beta-lactam antimicrobial agents against clinically isolated 131 strains of Haemophilus influenzae were studied. The peak of MICs of ampicillin (ABPC) was 0.20 microgram/ml. Those of cefaclor (CCL), cefotiam (CTM), cefteram (CFTM), cefpodoxime (CPDX), cefdinir (CFDN), cefditoren (CDTR), cefcapene (CFPN), and faropenem (FRPM) were 1.56, 0.39, 0.013, 0.05, 0.20, 0.013, 0.013, and 0.39 microgram/ml, respectively. The antimicrobial activities of CFTM, CDTR and CFPN were superior to those of others. There was 74.8% of ABPC-sensitive strains, of which the MICs were below 0.78 microgram/ml. The percentages of beta-lactamase-positive strains and beta-lactamase-negative ABPC-resistant H. influenzae (BLNAR) were 14.5% and 14%, respectively.

Anti-Bacterial Agents↗

[Hematopoietic stem cell transplantation for treatment of acute leukemia].

Recently, hematopoietic stem cell transplantation has been diversified and classified into several types of transplants, including allogeneic bone marrow, peripheral blood stem cell and cord blood stem cell transplantation (BMT, PBSCT, CBSCT), from related or unrelated donors. In addition, autologous BMT or PBSCT can be used to facilitate hematologic reconstitution after marrow-ablative therapy for hematologic malignancies. At least 50% of patients with acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL) can be cured by treatment with allogeneic BMT. Autologous BMT has been studied in comparison with allogeneic BMT or intensive chemotherapy in the treatment of AML and ALL. A series of large-scale prospective randomized studies have provided controversial results: relapse rates are significantly low, but treatment-related mortality is significantly high, after allogeneic or autologous BMT as compared to intensive chemotherapy. At present, it is somewhat difficult to determine which treatment modality is indicated as a postremission therapy for AML and ALL. Therefore, risk factors such as leukemia subtype, age, karyotype, and initial response should be taken into consideration when deciding on a postremission therapy. In the 1990's, the use of autologous PBSCT has been replacing autologous BMT, as autologous PBSCT has several advantages over autologous BMT. Consequently, allogeneic PBSCT has come to be increasingly used instead of allogeneic BMT in the treatment of leukemia. Recent clinical data clearly indicate that allogeneic PBSCT can be used as an alternative to allogeneic BMT. With well-designed clinical trials, the places, of allogeneic or autologous BMT and PBSCT will be clarified in the treatment strategy for acute leukemia.

Antineoplastic Agents↗

[Long-term follow-up study on sequelae of carbon monoxide poisoning; serial investigation 33 years after poisoning].

1. We examined 156 patients 33 years after CO poisoning occurred at the Miike Mikawa Mine, Fukuoka, Japan. The subjects were classified according to age as follows: between 55 and 59 years (n = 14), 60 and 69 years (n = 62), 70 and 79 years (n = 60), and 80 and 87 years (n = 18). The mean age was 69.2 years old. Concerning the duration of coma that occurred soon after the accident, 64 remained comatose from 0 to 6 hours, 46 from 6 to 12 hours and 46 from 12 to 48 hours. 2. Subjective symptoms were observed in 96.8% of the patients. Among them, forgetfulness was noted in 89.7%, followed by irritability in 66.7%, headache in 59.6%, insomnia in 55.8%, limb pain in 46.8%, dull head feeling in 42.9% and dizziness in 36.5%. 3. Intellectual disturbances were observed in 68.6% of the patients, including impression disturbance in 58.3%, memory disturbance in 51.9%, calculation disturbance in 63.5%, thinking disturbance in 61.5% and disorientation in 14.1%. 4. Apathy and disorder of volition and interest which were found in 72.4% were included in personality change because all symptoms persisted for many years. Personality change was classified as follows: weakness of emotion and will (hypobulia) in 54.4%, infantilism in 35.2%, hyperactive, talkactive and lack of inhibition in 18.5%, lack of self-possession and unstable temper in 9.6%, depression in 15.3%, neurosis in 7.6% and schizophrenic state in 2.5%. Among these symptoms of personality change, weakness of emotion and will and infantilism were conspicuous among the patients who remained in a coma for more than 6 hours soon after the accident but showed no relationship with age. 5. Neurological symptoms that were found in 48.7% of the patients were classified as sensory disturbance in 25.6%, peripheral nerve symptoms in 16.0%, pyramidal symptoms in 14.1%, ataxia and cranial nerve symptoms in 7.1%, paroxysmal symptoms in 6.4% and focal symptoms in 4.5%, extrapyramidal symptoms in 21.8% (Parkinsonism in 4.5%, tremor in 10.9% and muscle rigidity in 16.0%) and vegetative symptoms in 37.2%. 6. At the time of investigation, 5 CO poisoning patients were classified as serious cases (3.2%), 20 as comparatively serious (12.8%) medium-degree cases, 28 as comparatively mild (17.9%) medium-degree cases, 37 as comparatively serious (23.7%) mild cases, 42 as comparatively mild (26.9%) mild cases, 24 (15.4%) as having symptoms which were not problematic, and 24 (15.4%) as having symptoms that markedly worsened due to complication. 7. A total of 138 (88.4%) cases had complications were classified as follows: 78 cases (50.0%) of hypertension, 62 cases (39.7%) of cerebral infarction, 24 cases (15.4%) of cardiac disturbance, 21 cases (13.5%) of diabetes mellitus, 14 cases (9.0%) of hepatic disturbance and six cases of silicosis (3.8%). 8. Cranial MRI was carried out for 129 cases (82.7%). Of the abnormal findings identified, cerebral atrophy accounted for 72.0% (93 cases), including moderate and severe cases in 47.2% (61 cases), pallidum lesion for 37.9% (49 cases), lacunar infarction (including cerebral infarction) for 52.7% (68 cases), and hippocampal atrophy for 18.6% (24 cases). Many cases of cerebral atrophy and hippocampal atrophy were observed in patients who remained in the initial coma for more than 12 hours and were 80 years of age or old. The cases of pallidum lesion were observed in patients who remained in the initial coma for more than 6 hours, and no relationship with age was found. The other findings, cerebral atrophy and lacunar infarction showed a slight relationship with age. 9. Among the moderate and serious cases of intellectual disturbance, cerebral atrophy constituted to 62.5%, lacunar infarction 68.7% and pallidum lesion 50.0%. Among the moderate and serious cases of personality change, cerebral atrophy constituted 78.5%, lacunar infarction 35.0% and pallidum lesion 50.0%. Moreover, among extrapyramidal symptoms, pallidum lesion constituted 58.6%, cerebral atrophy 55.1% and lacun

Accidents, Occupational↗

[Changes in 24-hour urinary excretion of sodium and potassium in a community-based heath education program on salt reduction].

PURPOSE: To examine changes in urinary excretion of sodium, potassium and sodium/potassium ratio in a community-based health education program on salt reduction. SUBJECTS AND METHODS: The surveyed community was Kyowa town (census population in 1985 = 16,792) where we have conducted a community-based blood pressure control program since 1981 and health education on reduction of salt intake since 1983 for primary prevention of hypertension. A 24-hour urine collection was conducted for systematically selected samples of the participants aged 40-69 in cardiovascular risk surveys in 1982-86 (early period) and in 1990-94 (later period) to estimate changes in urine excretion of sodium, potassium, and sodium/potassium ratio. RESULTS: A 24-hour urine collection was available for 565 persons (410 men and 155 women) in 1982-86 and 1,461 persons (571 men and 890 women) in 1990-94. A decline in mean sodium excretion was larger in ages 40-49 than in other age groups, and for ages 40-69 combined, the decline was 0.9-1.1 g per day for men and women. Mean sodium excretion declined to 10 g or less per day for men and women aged 60-69. Mean potassium excretion did not change except for men aged 60-69 with an increase in potassium. Sodium/potassium ratio tended to decline for women aged 40-49, and declined significantly for other sex-age groups. A larger reduction in sodium excretion was seen among persons with a history of hypertension compared to those without it. CONCLUSIONS: A significant reduction in urinary excretion of sodium and sodium/potassium ratio was observed in a community-based health education program. Men and women aged 60-69 reached a recommended level of 10 g or less in sodium intake.

Adult↗

[An early phase II study of autologous peripheral blood stem cell transplantation for acute myelogenous leukemia in first remission. Japan Blood Cell Transplantation Study Group].

We performed a multicenter, an early phase II clinical trial to evaluate the feasibility, safety and efficacy of myeloablative therapy supported by autologous peripheral blood stem cell transplantation (auto-PBSCT) for the treatment of acute myelogenous leukemia (AML) in first remission. A total of 105 patients were enrolled in the study, and 56 patients in first complete remission received auto-PBSCT. The median age was 44 years. Of the 56 patients, 34 (60.7%) had M2 or M3 AML by the French-American-British Classification system. The median concentration of infused CD34+ cells was 2.3 x 10(6)/kg by recipient body weight. Median days to reach an absolute neutrophil count > 500/microliter and a platelet count > 20000/microliter were 14 and 16, respectively. The median disease-free survival rate was estimated to be 62.0% at a median follow-up time of 534 days. Although the study enrolled a small number of patients and the follow-up period was relatively short, the preliminary results were encouraging and indicated that myeloablative chemotherapy with auto-PBSCT is feasible and can be performed safely as a post-remission therapy for AML. A prospective randomized clinical trial of auto-PBSCT versus standard chemotherapy alone will be necessary to assess the efficacy of high-dose therapy facilitated by auto-PBSCT as a post-remission therapy for AML.

Adolescent↗

[A multicenter early phase II study of high-dose chemotherapy with autologous peripheral blood stem cell transplantation for treatment of intermediate-grade non-Hodgkin's lymphoma. Japan Blood Cell Transplantation Study Group].

We conducted a multicenter early phase II study to evaluate the feasibility and therapeutic efficacy of high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation (auto-PBSCT) for the treatment of intermediate grade non-Hodgkin's lymphoma (IG-NHL). High-dose etoposide or cyclophosphamide followed by G-CSF was used for PBSC mobilization, and a sufficient number of CD34+ cells (> 1 x 10(6)/kg) were collected. Out of 81 enrolled patients, 50 received high-dose chemotherapy with auto-PBSCT; Hematologic recovery after transplantation was rapid. The incidence of grade III/IV toxicity (Bearman) was about 6%; treatment-related mortality was 6% (3/50). The Disease-free survival rate for the patients in complete remission who received high-dose chemotherapy with auto-PBSCT was better than that for the patients who were treated with conventional chemotherapy (57% vs 35%). These preliminary results indicated that high-dose chemotherapy with auto-PBSCT is feasible and effective. A prospective randomized phase III clinical trial will be required to assess the efficacy of high-dose chemotherapy with auto-PBSCT as a post-remission therapy for IG-NHL.

Adolescent↗

[Nationwide survey of allogeneic peripheral blood stem cell transplantation from related donors in Japan: current trends and issues].

In December 1997, we conducted a nationwide survey of cases of primary allogeneic peripheral blood stem cell transplantation (allo-PBSCT) performed in Japan between December 1994 and November 1997 Data was collected on 103 patients with hematologic malignancies, aplastic anemia, or solid tumors. Eighty-seven patients received transplants from HLA-identical siblings, and 16 from HLA-mismatched related donors. Granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSC) were collected from donors by 1 to 3 aphereses. Apheresis products contained a median 5.4 (1.0-30.4) x 10(6) CD34 + cells/kg. Most patients were given cyclosporine and methotrexate for graft-versus-host disease (GVHD) prophylaxis. Median days to ANC > 500/microliter and platelets > 50,000/microliter were 13 (7-49) and 16 (10-94), respectively. Grade II-IV acute GVHD developed in 37/99 (37.4%) and chronic GVHD in 59/86 (68.6%) patients. The incidence of treatment-related mortality within 100 days after transplant was 16.1%. Fifty-five patients (59.6%) were alive after a median follow-up of 794 days. More patients and longer follow-up periods will be required to assess the efficacy of allo-PBSCT and evaluate graft-versus-leukemia effect along with the incidence of acute and chronic GVHD.

Adolescent↗

Analysis of circulating hematopoietic progenitor cells after peripheral blood stem cell transplantation.

We investigated the kinetics of posttransplant circulating progenitor cells (PTCPC) in the early phase after autologous (auto-) and allogeneic (allo-) peripheral blood stem cell transplantation (PBSCT). We analyzed the number of myeloid progenitor cells (CFU-GM) per 10 ml of peripheral blood (PB) on days 0 (just prior to transplantation), 1 (12-15 hours after completion of first transplantation), 2, 3, 5, 7, 10, 14, 17, 21 and 28 (after auto-PBSCT), and also additionally on day 35 after allo-PBSCT. A standard methylcellulose colony assay was used for analysing the number of CFU-GGM and BFU-E on all of the days. In addition, high proliferative potential-colony forming cells (HPP-CFC) of the harvested PBSC from donors and day 1 PB from recipients were assayed in 5 allo-PBSCT patients. Furthermore, a proportion of CD38- cells among CD34+ cells in the harvested PBSC and day 1 PB was evaluated by two-color flow cytometric analysis in 5 allo-PBSCT patients. The number of CFU-GM on day 1 ranged from 7 to 119 per 10 ml PB after auto-PBSCT, and from 15 to 61 per 10 ml PB after allo-PBSCT. After these transient increases, PTCPC diminished rapidly. Then, PTCPC emerged again on day 7 after auto-PBSCT and on day 10 or 14 after allo-PBSCT along with neutrophil recovery. A proportion of HPP-CFC among myeloid colonies from day 1 PB of recipients was significantly higher than that from the harvested PBSC from donors (65.6 +/- 12.7% vs. 17.4 +/- 13.0%, respectively, n = 5, P = 0.0013). In addition, two-color flow cytometric analysis revealed that the proportion of CD34+CD38- cells was significantly higher in day 1 PB of recipients than in the harvested PBSC from donors (57.5 +/- 17.6% vs. 11.7 +/- 4.9%, n = 5, P = 0.005). These observations suggest that both primitive and committed transplanted myeloid progenitor cells may circulate in the very early period following PBSCT.

Adult↗

Effect of intermittent liver ischemia on outcome in patients with hepatocellular carcinoma on liver cirrhosis.

The influence on postoperative liver function of intermittent normothermic hepatic ischemia in cirrhotic patients was studied retrospectively. The mean total ischemia time was 88 (range 30-140) minutes in the hemi-hepatic occlusion group, and 68 (range 10-187) minutes in the total occlusion group. There were no operative deaths due to hepatic failure. Postoperative liver function improved within 1 week of the operation. There was no significant difference in the incidence of postoperative complications between the groups. Thus normothermic hepatic ischemia is tolerated for up to 180 minutes in the cirrhotic liver when an intermittent technique (15 minutes clamped and 5 minutes unclamped) is used.

Carcinoma, Hepatocellular↗

IL-13 as well as IL-4 induces monocytes/macrophages and a monoblastic cell line (UG3) to differentiate into multinucleated giant cells in the presence of M-CSF.

The formation of multinucleated giant cells (MGCs) from monocytes/macrophages is controlled by various cytokines whose crucial roles are not fully understood. In this study, we found that interleukin (IL)-13 as well as IL-4 induced peripheral blood monocytes (PBMs) and monoblastic cell line, UG3, to differentiate into MGCs in the presence of macrophage colony-stimulating factor (M-CSF), while IL-2, IL-7 or IL-10 did not. The presence of M-CSF was essential to this MGC formation, because IL-3 or granulocyte-macrophage colony-stimulating factor (GM-CSF) could not replace M-CSF. IL-4 and IL-13 have been known to inhibit the formation of osteoclast-like cells in the presence of stroma cells or osteoblastic cells. But in our system without stroma cells, IL-4 or IL-13 induced some of characteristics of osteoclasts such as tartrate-resistant acid phosphatase (TRAP) activity, vitronectin receptor (vit-R) expression and resorptive activity for hydroxyapatite, but not the expression of receptors for parathyroid hormone or calcitonin. These results suggest possible involvement of IL-4 and IL-13 in MGCs and osteoclasts development, and UG3 may be useful to further investigate the roles of IL-4 and IL-13 in the formation and physiology of MGCs, and the relationship between these MGCs and osteoclasts.

Acid Phosphatase↗

Partially mismatched pediatric transplants with allogeneic CD34(+) blood cells from a related donor.

This was a phase I, multi-center study of 13 pediatric patients (median age, 11 years) to evaluate toxicity, hematopoietic recovery, and graft-versus-host disease (GVHD) after allogeneic transplantation of enriched blood CD34(+) cells obtained from genotypically haploidentical but partially HLA-mismatched related donors (8 parents and 5 siblings). With regard to rejection, donor HLA disparity was 1 (5), 2 (6), or 3 loci (2). With regard to GVHD, recipient HLA disparity was 0 (1), 1 (3), 2 (8), or 3 (1). The patients suffered from acute myelogenous leukemia (6), chronic myelogenous leukemia (4), acute lymphoblastic leukemia (2), or hemolytic anemia plus immunodeficiency disorder (1). To reduce the risk of graft failure through the infusion of a large amount of stem cells, peripheral blood cells (PBC) were mobilized by recombinant granulocyte colony-stimulating factor (G-CSF; lenograstim, 10 microgram/kg/d for 5 days) and collected by 2 to 5 aphereses. To both enhance engraftment and reduce GVHD, CD34(+) cells were enriched using immunomagnetic procedures with the Baxter ISOLEX 300 system (Baxter Healthcare Corp, Irvine, CA) and cryopreserved. After variable cytoreductive regimens, a median of 7.7 (range, 2.2 to 14) x 10(6)/kg of CD34(+) cells and 1.03 (0.05 to 2.09) x 10(5)/kg CD3(+) cells were infused. Using Center-specific posttransplant supportive care and immunosuppressive GVHD prophylaxis, two patients experienced early death; one from veno-occlusive disease at day 17 and one from sepsis at day 18. Nine of 11 patients showed signs of engraftment; however, subsequent rejection was seen in 4 patients, 2 of whom had autologous recovery. Eight patients were evaluated in the early phase of marrow recovery. The median number of days to achieve an absolute granulocyte count of 0.5 x 10(9)/L was 14 (range, 9 to 20) and that to achieve a platelet count of 20 x 10(9)/L was 17.5 (range, 12 to 23). Donor chimerism persisted in five patients until death or current survival. All of the surviving patients with functioning-donor-type hematopoiesis were given total body irradiation. De novo acute GVHD (grades II and IV) was observed in two of the eight evaluated patients. Scheduled donor lymphocyte infusion (DLI), using the CD34(-) fraction, was administered to four patients, free of de novo acute GVHD, beginning between 28 to 43 days after transplant. Three of these patients developed acute GVHD (grades I, II, and IV). Cytomegalovirus infection was a major infectious complication but was successfully managed with gamma-globulin and gancyclovir treatment with or without additional DLI. Five patients are currently surviving, free of disease, with a follow-up ranging from 476 to 937 days. Each survivor has functioning hematopoiesis, three of donor origin and two of autologous origin. In conclusion, our results show that enriched blood CD34(+) cells from a mismatched haploidentical donor are a feasible alternative source of stem cells, but do not appear to ensure engraftment. Because none of the patients who were administered DLI survived, the therapeutic efficacy and safety of periodic DLI, as an integrated part of such transplants, needs to be clarified in further studies.

Adolescent↗

Genetic alterations in the retinoblastoma protein-related p107 gene in human hematologic malignancies.

Genetic alterations in the p107 gene, a close relative of the retinoblastoma tumor suppressor gene, have never been identified in human malignancies. When we searched for such alterations in human hematologic malignancies by Southern blot analysis, 2 of 21 cell lines and 1 of 88 primary disorders had genomic alterations within the gene. Particularly, an altered p107 gene in a diffuse-large B-cell lymphoma cell line, KAL-1, harbored an intragenic deletion of about 15 kbp leading to the expression of an altered p107 mRNA devoid of 819 nucleotides of the coding sequences, which predicts to encode an approximately 87-kDa protein. This cell line was found to express solely a p107 derivative of 84 kDa by immunoblotting analysis. These results suggest that alterations in the p107 gene are probably related to a limited subset of human hematologic malignancies.

Gene Deletion↗