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A 61-year-old man was referred to our hospital for leukocytosis and thrombocytopenia. Bone marrow examination showed hypercellular bone marrow accompanied by dysplasia, and the karyotype of his bone marrow cells was 46,XY, der(5;12)(q10;q10), +mar,inc[3]/46,XY[12]. A diagnosis of myelodysplastic syndrome, unclassifiable, was made. Analysis of major BCR/ABL1 chimeric RNA by real-time polymerase chain reaction method was positive, and then Ph chromosome was observed afterward. His Ph chromosome was seen in der(5;12)-negative cells analyzed by FISH, which suggested the late-appearing Ph chromosome evolved into another clone. Despite treatment containing imatinib, hydroxyurea, and cytosine arabinoside, he died due to respiratory dysfunction 5 months after the initial diagnosis. The autopsy revealed massive pulmonary infiltration by Ph-negative cells, suggesting MDS-derived clones. It has been reported that the late appearance of Ph chromosome associates with leukemic progression. Although the incidence of late-appearing Ph chromosome is estimated to be relatively low, further accumulation of cases is necessary for the evaluation of its impact on prognosis and disease progression.

We present three long-term survivors treated with high-dose melphalan with autologous peripheral blood stem cell transplantation(auto PBSCT)for primary AL amyloidosis. Because melphalan toxicity is dose-related, patient age and the extent of organ involvement are very important factors for the success of high-dose melphalan treatment with PBSCT. The patients were therefore given high-dose melphalan using the risk-adapted approach to melphalan dosing. They received 3 courses of a vincristine, doxorubicin and dexamethasone(VAD)regimen, along with high-dose melphalan(100-200mg/m2)with auto PBSCT. There were no serious complications or transplantation-related mortalities. Patients survived for an average of 68 months(22-100 months)in partial response. A risk-adapted approach to melphalan dosing with PBSCT is an effective treatment in patients with primary AL amyloidosis.

A 65-year-old man was admitted to a local hospital with symptoms of unstable angina pectoris. He was administered ticlopidine before drug eluting stent (DES) stenting for 2 weeks. Coronary angiography showed 3 vessel diseases. He was then admitted to our hospital due to a sudden onset of unstable angina following shock during the percutaneous coronary intervention (PCI) procedure, emergency off-pump coronary artery bypass grafting (OPCAB) was thus performed. He received aprotinin 5 hundred thousand KIU just at the start of surgery and 5 hundred thousand KIU after undergoing anastomosis of the coronary artery. Postoperatively, only some minor bleeding was observed. Aprotinin reduces bleeding, the transfusion requirements of packed red blood cells, platelets, and the total blood units in patients on ticlopidine who undergo emergency OPCAB.

A 65-year-old man underwent a successful repair of a posterior ventricular septal perforation (VSP) 9 days after suffering an acute inferior myocardial infarction. After hospitalization, his hemodynamic condition gradually worsened, in spite of administering intensive medical therapy. Emergent operation was performed on the 4th day after onset. An equine pericardial patch was sutured around the VSP through the right ventricular side of the septum using the double-patch repair method and the right ventricular wall was closed as using the standard extracorporeal perfusion technique. The dimensions of the VSP measured 5 mm in diameter. Transesophageal echocardiography was performed on the 14th postoperative day. Cardiac catheter examination was done on the 18th postoperative day. No residual shunt was recognized and cardiac function was good. He was discharged on the 20th postoperative day. The occurrence of a posterior VSP is comparatively rare, and repair of VSP is difficult to perform during an acute period. Therefore, the operative results of VSP cases remain poor.

High-dose chemotherapy followed by autologous peripheral blood transplantation (HD-APBSCT) is a therapeutic option for patients with non-Hodgkin's lymphoma (NHL) after complete remission (CR) as consolidation therapy. In this report we describe a retrospective study of such treatment. A total of 38 patients with NHL were treated between November 19 9 1 and March 2005. At five years,the rate of disease-free survival (DFS) and overall survival (OS) was 64.3% and 66.5%, respectively. Patients who underwent transplantation in first CR had a 5-year probability of disease-free survival of 71.6% compared with 35.7% for those who were in second CR at the time of transplantation (p=0.10). In a monovariate analysis, second CR status at the time of transplantation was a relatively adverse predictor of DFS. None of those factors containing surface markers were significantly associated with clinical variables such as the CR status at the time of transplantation. Thirty high intermediate risk and high risk patients with aggressive B-cell lymphoma had a better outcome than patients treated with standard chemotherapy. In this study, 8 patients with T-cell lymphoma had a 3-year DFS and OS of 87.5% and 87.5%, respectively. HDT-APBSCT is a candidate for consolidation therapy for high-intermediate risk and high risk patients with aggressive B-cell and T-cell lymphoma.

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.

We experienced the VNCOP-B (etoposide, mitoxantrone, cyclophosphamide, vincristine, predonisolone, bleomycin) combination regimen for the treatment of elderly patients with aggressive non-Hodgkin lymphoma (NHL) in a multicenter study by 6 collaborative institutions. Patients were previously untreated > or = 60 years of age and received prophylactic G-CSF. Twenty patients entered this trial, and all of them were evaluated for feasibility, toxicity, and efficacy. The complete remission rate was 75.0%, with a 100% overall response rate; overall survival (OS) rate at 3 years was 79.1% (median follow up 761.5 days), with a 60.7% progression-free 3-year survival (PFS) rate (median follow-up 600.0 days). Our trial was promising and well-tolerated. According to IPI, high/high-intermediate risk was associated with significantly worse OS and PFS than low/low-intermediate risk (2-year OS: 51.8% versus 100.0%, p=0.0118; 2-year PFS: 33.3% versus 80.0%, p=0.0125). Grade 3/4 infections occurred in 3 patients, but no patients experienced it with predonisolone reduced.

Cardiac myxoma of right ventricle is rare. We report a 16-year-old girl who underwent an emergent surgical resection of right ventricular myxoma. She had syncopal attach in going to school and was referred to our hospital in emergency. There were no abnormal findings in brain computed tomography (CT) and electroencephalogram, but Levine IV/VI systolic ejection murmur was heard. Echocardiography and magnetic resonance imaging (MRI) revealed the presence of large mass in the right ventricle which was floating into the pulmonary artery. The tumor was removed completely through the both of main pulmonary artery and right atrium using cardiopulmonary bypass. The tumor was attached to the right ventricle free wall by a pedicle, which was 5 x 3 cm in size and was diagnosed as myxoma by histopathological examination.

We report four cases with spinal non-Hodgkin's lymphoma (3 male and 1 female, 33 to 58 years old). On administration, back pain progressing to paraplegia was observed in all cases. Sphincter dysfunction was observed in two cases. Magnetic resonance imaging (MRI) studies were most useful for the clinical diagnosis of spinal lymphoma. Diffuse large B cell lymphoma was revealed from immunohistochemical studies of bone biopsies. The patients' clinical stagings were IV in three and I E in one case. One case treated by surgery followed by chemotherapy (CMT) and radiation therapy (RT) resulted in progressive disease. RT followed by CMT was given in the other cases. Two cases showed a partial response and one died from progressive disease. In all cases, either surgical or radiation therapy was helpful for the amelioration of the patients' progressive paraplegia and sphincter dysfunction.

We report 2 cases of bronchus-associated lymphoid tissue lymphoma (BALT lymphoma), which is a rare disease. Patient 1 was a 76-year-old woman with a chief complaint of cough. Since plain chest radiography revealed an abnormal shadow in the hilum of the lung, she visited our hospital. Patient 2 was a 56-year-old man, who had been diagnosed as having pseudolymphoma at a medical check-up in a local hospital. During follow-up, however, he was referred to our hospital because of enlarged tumors and chest pain. In both patients, bronchofiberscopy demonstrated submucosal tumors and biopsy samples showed formation of lymphoepithelial lesions by centrocyte-like cells with a B-cell staining pattern. The patients were therefore diagnosed as having BALT lymphoma. Both received CEOP-E treatment, which improved the clinical symptoms but did not result in complete remission. The patients have been followed up after discontinuation of the medication. The progress of the disease has been slow, and both patients are alive as of September 2001.

Peripheral blood stem cells can be stored by the following 3 methods: liquid storage, non-rate controlled freezing and rate controlled freezing. Methods of processing of these cells including thawing, ex vivo purging and infusion are described in detail.

The frequency of infection in recipients of allogeneic bone marrow transplants (BMT) who received oral new quinolones (NQ) was compared with that in BMT recipients who were given oral vancomycin/tobramycin (V/T). Between 1984 and 1997, our hospital treated 79 patients with V/T and 90 patients with NQ. Number of febrile days, duration of intravenous antibiotics administration, and frequency of documented infections were statistically the same for both groups. However, the frequency of grampositive bacterial infections, especially staphylococcal infections, was slightly higher in patients receiving NQ than in patients receiving V/T (p = 0.12). Of the patients who received NQ, those who underwent unrelated donor BMT procedures were generally febrile for slightly longer periods than those who underwent related donor BMT procedures (p = 0.10). These results suggest that oral NQ is as effective as oral V/T for the prevention of serious gramnegative bacterial infections in patients who undergo BMTs.

We analyzed the distribution of two T cell subsets, CD8+ CD11a+ (CD8+ cytotoxic effector population) and CD8+ CD57- cells, in the peripheral lymphocytes of 3 post-operative patients with post-transfusion graft-versus-host disease (PT-GVHD) and 5 post-operative patients without PT-GVHD. The percentage of CD8+ CD11a+ cells in the PT-GVHD-negative control was 19 +/- 4%, and in the 3 patients with PT-GVHD, 69%, 66%, and 59%, respectively. The percentage of CD8+ CD57- cells in the PT-GVHD-negative control was 19 +/- 6%, and in the 3 PT-GVHD patients, 59%, 58%, and 55%, respectively. Significantly higher proportions of the two T cell subsets were consistently observed in the patients with PT-GVHD than in the PT-GVHD-negative control. These results suggest that the analysis of CD8+ T cell subsets may be useful for the simple and rapid laboratory diagnosis of PT-GVHD.

Sixty-two episodes of fungemia which occurred in patients with hematological disorders between 1976 and 1996 in our hospital were analyzed with respect to background and prognostic factors. Forty-four of the patients were male and 18 were female. The underlying diseases were acute leukemia in 36 cases, chronic myelogenous leukemia in 9, malignant lymphoma in 9 and others in 8 cases. Trichosporon beigelii and Candida tropicalis were the most frequently isolated fungal pathogens. The prevalence of C. crusei increased while that of C. albicans decreased after 1988. Fuungemia frequently occurred in patients with following factors: 1) advanced disease, such as relapse of acute leukemia or malignant lymphoma or blast crisis of chronic myelogenous leukemia; 2) neutrophil count less than 100/microliter; 3) administration of antibiotics; 4) focal infection, gastrointestinal hemorrhage or urinary catheterization; and 5) isolation of causative organisms from surveillance cultures obtained just before the onset of fungemia. The mortality rate of patients with fungemia was 74%. Absence of hypotension, increased neutrophil count for a week after the onset of fungemia, and the intravenous administration of Amphotericin B (AMPH) were good prognostic factors. Fungemia frequently occurred in patients with advanced disease and had a very poor prognosis. These results emphasized the importance of isolation of fungus from surveillance cultures, early initiation of AMPH administration, and attempts to increase neutrophil counts with G-CSF and other measures for improving the prognosis of fungemia in patients with hematological disorders.

Tsutsugamushi disease is widely spread throughout Japan. A case of tsutsugamushi disease was seen in October, 1996. A 64-year-old male developed typical symptoms of tsutsugamushi disease with Rickettsia tsutsugamushi, after he returned to Japan from Cheju Island, Korea. Not only in Japan but also in other Asian countries including Korea, China, Taiwan, and Thailand, tsutsugamushi disease is one of the most important rickettsial diseases carried by ticks or mites. If a traveller returning from an Asian country has symptoms such as high fever, skin eruption, and lymphadenitis, we should suspect that he is suffering from tsutsugamushi disease and should search if he has an eschar on any area of his body. We should not forget that tsutsugamushi disease is an imported disease. Patients of tsutsugamushi disease often have hematological disorders. They are sometimes referred to the hematological section of the hospital. Hematologists should be familiar with this disease.

We investigated the therapeutic efficacy and safety of cefpirome sulfate (CPR) in treatment of hematopoietic disorder-associated infections. A total of 219 patients were admitted to 12 hospitals of Hanshin Study Group of hematopoietic disorders and infections between April 1994 and March 1996 and were enrolled in this study. Most patients received intravenously infused CPR at a dose of 1 or 2 g twice a day for 3 days or more. Twenty nine patients dropped out or were excluded and remaining 190 patients were adopted for the evaluation. A overall response rate was 58.4% (111/190). Among neutropenic patients, the response rate was 50% (8/16) in patients whose peripheral neutrophil counts (PNC) remained less than 100/microliter throughout the observation period and was 53.7% (22/41) in patients with PNC remained less than 500/microliter. In contrast, in patient whose PNC was below 500 before the treatment but exceeded 501/microliter during of at the end of the treatment, the response rate was as high as 78.4% (29/37). When G-CSF was combined, the response rate became significantly (P < 0.05) higher, 68.5% (50/73), as compared with that, 52.1% (61/117), in patients without it. In cases in which the causative organisms could be identified, the organisms were eliminated in 81.8% (9/11) of the patients infected with Gram-positive bacteria, whereas in 100% (12/12) in those infected with Gram-negative bacteria. Skin eruption developed in 6 patients during the treatment with CPR, and vascular pain and parosmia in one each other. These symptoms subsided soon after discontinuation or even without discontinuation of CPR. Abnormal laboratory findings, mainly liver dysfunction, i.e. elevation of slight degree of serum transaminase levels, were observed. The values, however, turned to normal immediately after the cessation or completion of the treatment. In conclusion, CPR is considered to be an antibiotic of value with high efficacy and safety in treatment of hematopoietic disorder-associated infections.

We clinicopathologically reviewed cases of clear cell adenocarcinoma (CCA) of the endometrium and adenocarcinoma of the endometrial type mixed with a clear cell component (AMC). 1. Among 1,152 cases of endometrial carcinoma, CCA and AMC were found in 16 (1.4%) and 21 (1.8%) cases, respectively. 2. As revealed by cumulative survival rates based on the Kaplan-Meier method, the prognosis was significantly poorer in CCA and AMC than in endometrial carcinoma (p < 0.001). 3. As for the subtype of CCA, 5 (31%), 9 (56%) and 2 (13%) cases were papillary, solid, and tubulocystic, respectively. 4. The frequency of epithelial hyaline body, bizarre nucleus, psammoma body, necrosis, lymphoplasmacytic infiltration, lymphatic invasion, vessel invasion, and atypical hyperplasia among cases of CCA was 8 (50%), 7 (44%), 5 (31%), 6 (38%), 8 (50%), 5 (36%), 4 (29%) and 1 (7%) cases, respectively. Histologically, lymphoplasmacytic response was the most closely correlated with the prognosis. 5. Among the cases of AMC, there were 6 cases of metastasis and recurrence. In 5 (83%) of these, the clear component increased markedly in metastatic and recurrent lesions although the component was very minor in the primary lesions.

Two hundred eighty-seven episodes of septicemia which occurred in patients with hematological disorders between 1980 and 1993 were examined according to respective underlying diseases. The diagnosis of acute myelogenous leukemia (AML) was made in 155 patients, acute lymphocytic leukemia (ALL) in 45, chronic myelogenous leukemia (CML) in 29, malignant lymphoma in 36, adult T-cell leukemia (ATL) in 7, multiple myeloma (MM) in 8 and aplastic anemia (AA) in 7. Three hundred and two strains were isolated from 287 patients. Fifty two point three percent of the total isolates were gram-negative bacilli, 26.8% were gram-positive cocci, 17.2% were fungi and 3.6% were anaerobic bacteria. In ALL patients gram-positive cocci accounted for 42.0%. This rate was significantly higher than in other disorder. Additionally, oral mucositis or gingivitis was evaluated as clinical background in 36.1% of ALL cases. Forty-seven point two percent of organisms which caused septicemia in ALL patients were isolated from surveillance cultures of the throat just before the onset of septicemia. These data suggested that in ALL cases microbiological organisms more frequently invaded through injuries of oral mucosa. In ATL, CML, MM and AA patients, fungi accounted for more than 25% of causative organisms. The most common organism of all of the strains was Pseudomonas aeruginosa (21.9%), but in ATL and MM patients Escherichia coli was more common than P. aeruginosa. At the onset of the septicemia, neutrophil counts were less than 100/mm3 in 76.6% of all patients, and more than 3,000/mm3 in only 5.0%. In contrast to this result, in 66.7% of ATL patients and 37.5% of MM patients, septicemia occurred even when neutrophil counts were more than 3,000/mm3. Septicemia occurred in 28.2% of the total patients but died. The mortality rate in MM and AA patients (50.0% respectively) was higher than in other diseases. According to the mortality of each causative organisms, fungal septicemia had a terribly high mortality of 82.9% while other bacterial mortality was about 20%.

The effects of tamoxifen (TAM) on 56 postoperative breast cancer patients who were orally administered TAM and followed up at Cancer Institute Hospital from 1989 to 1992 were studied retrospectively. The maturation index (MI) and karyopyknotic index (KPI) were employed to investigate the effects of TAM on vaginal epithelial cells cytologically, and the patients were also monitored for complications. The results were as follows. (1) The relationship between the duration of TAM therapy and the changes in MI and KPI were analyzed. It was found that, for the MI, intermediate cells (IMT) increased and superficial cells (ST) decreased during TAM administration for up to 4 years, but when the TAM therapy was continued for longer than 4 years, IMT showed a gradual decrease and ST increased gradually. The KPI values showed similar changes. (2) Studies of the endometrium (26 cases) revealed a tendency for few of the long-term administration cases to show a picture of atrophy. Of the total of 56 patients, endometrial lesions were observed in five cases (8.9%), consisting of endometrial cancer in three and cystic glandular hyperplasia in two. The mean duration of TAM administration to these five patients was 54 (+/- S.D.26.8) months. These data indicate that long-term oral administration of TAM involves the possibility of having an estrogenic effect on the vaginal epithelium and the uterine endometrium.

The natural history and biological behavior of cystic glandular hyperplasia (CGH), which has been considered to be a precursor of endometrial carcinoma, still remain unclear. The present prospective study included 52 patients with CGH, who were followed up for 6 months to 5 years with occasional curettage, surgical procedures or hormonal therapy. The lesion disappeared in 35 cases (67.3%), persisted in 12 cases (23.1%) and became more serious in 5 cases (9.6%). Of these 5 cases, one case was found to have endometrial carcinoma during her follow-up. Nuclear DNA analysis was performed by Flow cytometry in 8 CGH cases. Eighty four point nine % of the cells from these 8 cases were in G0+1 phase, 8.3% in S phase and 7.4% in G2 + M phase. The proliferation index for CGH was 15.7%. Proliferative and mitotic activities of CGH were found to be similar to those of adenomatous hyperplasia, and the levels of these activities were between those of normal endometrium and atypical hyperplasia.G1.

Eighteen patients underwent allogeneic bone marrow transplantation (allo. BMT) during the period May, 1991 to December, 1992 in the Center for Adult Diseases, Osaka. They were monitored for cytomegalovirus (CMV) antigenemia and arterial oxygen saturation (SaO2). More than 10 antigen-positive cells per 50,000 polymorphonuclear leukocytes were detected in five of 18 patients. Three of these 5 patients developed CMV pneumonia several weeks after the first detection of more than 10 positive cells. Six of 18 patients developed interstitial pneumonia (IP) (3 CMV pneumonia and 3 idiopathic IP). SaO2 decreased less than 95% several days before the development of IP in 3 of these 6 patients (2 of CMV pneumonia and 1 of idiopathic IP). CMV antigenemia assay and SaO2 assay were thus both considered to be useful for the early detection or prediction of development of CMV pneumonia.

This manuscript reports Bacillus cereus sepsis in two cases with acute myelogenous leukemia (AML) who suffered complications of fatal intracranial hemorrhage during remission induction therapy. The first case was 43-year-old male with AML (M0) receiving first consolidation chemotherapy who developed sudden diarrhea, abdominal pain and spiking fever. Two days later, he died of intracranial hemorrhage. The second case was 15-year-old male with AML (M5b) who was receiving first induction chemotherapy. He developed headache and vomiting following spiking fever and diarrhea. He died of subarachnoid hemorrhage the next day. In both cases, Bacillus cereus was isolated from blood culture. Fatal intracranial hemorrhage due to severe bleeding tendency caused rapid to death in both cases. These bleeding tendencies might have been induced by B. cereus sepsis. In addition, we should not overlook B. cereus as contamination, but rather consider it as a potential pathogen, when isolated from blood culture.

Blood erythropoietin (EPO) concentration was measured by radioimmunoassay in 513 patients with various diseases. Untreated polycythemia vera showed lower EPO concentration than normal. Aplastic anemia (AA) revealed the highest EPO level among all anemic diseases in relation to hematocrit value. EPO level of AA patients who underwent bone marrow transplantation was as low as normal subjects even when the anemia has not fully recovered. Paroxysmal nocturnal hemoglobinuria (PNH) showed unusually high EPO concentration among hemolytic anemias. In normal subjects, blood EPO concentration showed a diurnal rhythm that was higher at night than during the daytime. These findings suggest the diagnostic usefulness of measurement of EPO in blood diseases.

The first choice for the treatment of gastric cancer is surgery. Presently, endoscopic therapy offers the possibility of cure for some types of early gastric cancer, especially among aged or poor surgical risk patients and has obtained excellent results. During the past 13 years and 6 months from April 1978 to September 1991, 55 lesions in 52 patients aged over 75 years old were treated by endoscopic therapy. During this same period, 57 patients aged over 75 years old were surgically treated for early gastric cancer. In this study we evaluated the efficacy of endoscopic therapy for the treatment of early gastric cancer, and furthermore we compared endoscopic therapy with surgery in relation to prognosis, complications and quality of life. The analysis of endoscopic treatment showed that in 72.7% of our cases local cure was obtained. Generally, early gastric cancers less than 20 mm, of well differentiated type, restricted to the mucosa and without ulceration are suitable for endoscopic therapy. Local cure could be achieved in more than 90% of these cases. Among the 52 patients treated by endoscopic therapy, there were residual lesions after treatment in in 4 patients. They died of advanced disease or metastatic liver tumor. These patients were poor surgical risks and for this reason surgery was contraindicated. Analysis by the Kaplan-Meier method showed that in comparison with conventional surgery, endoscopic therapy showed better results in the first two years of follow up and almost the same results after three years.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum erythropoietin (EP) concentration was measured by the recombinant EP-based radioimmunoassay and was examined to standardize the hemoglobin (Hb) related level of 144 normal control and 56 patients with iron deficiency anemia and hemolytic anemia excluding paroxysmal nocturnal hemoglobinuria. The standardization was achieved by logarithmic regression of the EP titier on Hb either by the two-phase linear form or by the third degree sigmoid form at a 95% confidence limit for each regression. The third degree regression was found to be preferable from the view point of both statistics and the negative feedback mechanism. The average and scattering of the deviation from the standard level thus determined of the disease groups indicated that the EP level is: (1) 12 fold higher than the standard level in 42 aplastic anemias (the most in excess and a few in standard). (2) three fold higher than that in 27 myelodysplastic syndromes (relatively higher dispersed state). (3) 29% of the standard level in 33 anemias associated with chronic renal failure (deficient state). (4) 105% of the extrapolated standard level in 22 polycythemia veras (standard state). The standardization of Hb-related Ep titer may provide new pathophysiological approaches in a variety of hematopoietic disorders.

One hundred thirty-eight patients with severe infections accompanying hematological diseases were treated with cefodizime (CDZM). CDZM was administered by intravenous injection at daily doses ranging from 2 g to 8 g for about 3 to 18 days. Clinical efficacies of CDZM were excellent in 30 cases, good in 37 cases, fair in 1 case and poor in 53 cases. The efficacy rate was 55.4%. The efficacy rate was 56.4% in patients from whom causative organisms were not identified. The efficacy rate against Gram-negative bacteria (66.7%) was higher than that against Gram-positive bacteria (28.6%). No significant differences in the efficacy rates were found among groups of patients with different initial neutrophil counts (less than 100, 100-499, and over 500/microliters). Skin eruption caused by CDZM was observed in 2 patients (1.5%). Hepatic disorders, renal dysfunction and urinary test abnormality (protein and urobilinogen) were observed in 7 (5.0%), 1 (0.7%) and 1 (0.7%), respectively. Therefore, CDZM was considered to be a clinically useful antibiotic for severe infections complicated with hematological diseases.

We encountered two cases of patients who showed vocal cord dysfunction and bronchial asthma. By using an ++astograph , we found that bronchial responsiveness of these ailments differed. In the case of vocal cord dysfunction, bronchial responsiveness to methacholine indicated a false high level by adduction of the vocal cord. Therefore other evaluations including pulmonary function and bronchoscopy were required to distinguish it from bronchial asthma. On the other hand, in the case of bronchial asthma, bronchial responsiveness to methacholine was mild, but life threatening asthmatic attack occurred after inhalation of methacholine. Psychological factors were not neglected in considering both of these cases. Therefore we must consider these results and psychological factors when evaluating bronchial responsiveness.

A 19-year-old psychologically disturbed female was admitted to our hospital because of intractable dyspnea and wheezing for twenty two months. She had been diagnosed as having asthma and had received several medications including steroids before admission to our hospital. According to our clinical observations, she was considered not to have asthma because neither FEV1.0 nor PaO2 was decreased during the periods of wheezing and FEV1.0 was not changed by inhalation of bronchodilators, although she had a family history of allergy and false bronchial hyperreactivity by asthograph. On physical examination, diffuse wheezing was heard mainly over the larynx during inspiration at the times of dyspnea. There was flattening of the inspiratory flow-volume loop during wheezing. Bronchoscopy performed during an attack confirmed that wheezing was due to adduction of the vocal cords throughout the respiratory cycle. Therefore, this case was diagnosed as vocal cord dysfunction. Her symptom was considered to be a form of conversion reaction derived from her unhappy past history. Following psychosomatic therapy, all of her medications became unnecessary. She understood the mind-body relationship of her condition, and learned to achieve self-control.

We investigated the quality of life (QOL) in 72 patients with bronchial asthma who are under our gradational psychosomatic treatment (GPT) by means of an 11-item questionnaire. The results were summarized as follows: 1) Ninety-two percent of the subjects showed a good understanding of mind-body relations and modified their stressful adaptive patterns. 2) Asthmatic symptoms improved in 86 percent of the subjects. Other symptoms also improved in 72 percent of the subjects. 3) In 81 percent of the subjects, their daily life improved. Furthermore 96 percent of the subjects obtained some advantages through GPT. 4) There were various improvements in psychological states, personal relations and life style in most of the subjects. 5) The attitudes of their families toward the patients improved in 46 percent of the subjects, however 71 percent of the families developed a better understanding of the cause of asthma from the psychosomatic point of view. 6) Most of the subjects with moderate or severe symptoms were considered to have reduced the grade of severity of their symptoms from the doctor's standpoint.

The degree of dyspnea when using metered-dose inhalers (MDIs), and the relationship between subjective self assessments and objective peak expiratory flow rates were examined by means of visual analogue scales and mini wright peak flow meters in 16 subjects with asthma. Three subjects who were neurotic in character were found to have a poor perception of the degree of airway obstruction after inhalation compared with objective changes in their condition. Two subjects, one neurotic and one alexithymic, assessed the degree of dyspnea to be worse after inhalation, when objectively there were few changes. However, one neurotic subject perceived an improvement in his condition when, in fact, there was little change. Furthermore, some severe cases used MDIs in the rogressive state of airway obstruction. In conclusion, we must pay attention to patients' characters when determining treatment in order to prevent overuse of MDIs or delays in treatments including the use of MDIs.

Early phase II study of MST-16[4,4-(1,2-ethanediyl) bis (1-isobutoxycarbonyloxy-methyl-2, 6-piperazinedione], a derivative of ICRF-154, on malignant lymphoma was conducted by multi-institutional cooperative group. MST-16 was administered orally at doses of 1,600 mg/body/day for 5 days or 1,200 mg/body/day for 10-14 days, mainly. The number of registered and evaluated patients were 29 and 28, respectively (Hodgkin's disease 3 patients and non-Hodgkin lymphoma 25). Twenty-seven of 28 patients had received prior chemotherapy and/or radiation therapy. Of 28 evaluable patients, overall response rate (CR + PR) was 32.1%. In high-dose administration group, the response rate was not significantly high. The response rate seemed to be high in patients who were treated repeatedly (number of courses greater than 3). Major side effects observed were myelosuppression and gastro-intestinal disorders which were reversible in a rest period. Myelosuppression seemed to be severe in high-dose administration group. This study indicated that MST-16 was a useful agent against malignant lymphoma including primary resistant or relapsed patients, and that the recommended regimen for a late phase II study was considered to be 1,600-2,400 mg/body/day for 5-7 days repeatedly with a pause of several days. Furthermore, the study should be considered at the dose of 3,200 mg/body because half cases administered at this dose showed some response.

We investigated the use of metered-dose beta agonist inhalers (MDIs) by means of 17-item questionnaires from the standpoint of psychosomatic medicine in 56 subjects with bronchial asthma. The results can be summarized as follows: 1) Many asthmatics with neurotic characters used MDIs frequently; Thirteen percent of them suffered adverse effects. The number of times the inhalers were used increased in proportion to the severity and the duration of illness. Fifteen percent of the subjects used MDIs frequently because of anxiety. 2) Fifty percent of the subjects, most of them had neurotic or alexithymic characters, used MDIs without suffering from dyspnea or wheezes; the subjects who used MDIs because of anxiety increased in proportion to the duration of illness. 3) Seventy eight percent of the subjects were anxious about asthmatic attack when they did not carry any MDI; sixty two percent of the subjects, most of them had neurotic or alexithymic characters, actually experienced asthmatic attack. 4) Seventy three percent of the subjects used MDIs secretly; sixty percent of the subjects did not like to inhale in the presence of others. 5) There were some subjects who acted incorrectly on or after asthmatic attack when MDIs were not effective.

Twenty mg of sizofiran (Schizophyllum glucan: SPG) was i.m. administered one day prior to surgery, or the same dose was injected 8 days and one day before surgery to 40 patients with cervical cancer and 15 with a benign tumor. Frozen sections of fresh pelvic lymph nodes from these patients obtained during surgery were stained by the ABC (Avidin-biotin-peroxidase complex) method with several monoclonal antibodies to define the surface phenotype of mononuclear cells. SPG led to a great increase in the number of cells stained with interleukin-2 receptor (IL-2R) and Leu 3a antibodies, mainly in PC, but with only a slight increase in the number of cells stained with Leu 2a, 7, 11, and M3 antibodies. This augmenting effect was more prominent in patients receiving two SPG injects that in those with a benign tumor. These results suggest that stimulus with some antigen (cancer antigen in the present study) may be required to induce immuno-augmentation by SPG which has no antigenicity. Interestingly, the above augmenting effects could be seen even in metastatic lymph nodes from advanced cervical cancer patients. SPG was thus revealed to be a potent biological response modifier leading to augmented helper T (Th) cell functions of pelvic lymph nodes in cervical cancer patients, among which an enhanced IL-2/IL-2R system was noted.

Twenty-five patients with cervical cancer (4 post-operative cases with FIGO stage Ib or IIb, 2 with stage IV, and 19 recurrence) were treated with a new BOMP consisting of bleomycin (5 mg/body, drip, i.v., days 1-7), vincristine (0.7 mg/m2, bolus, i.v., day 7), mitomycin-5 (7 mg/m2, bolus, i.v., day 7) and cisplatin (10 mg/m2, drip, i.v., days 1-7). The mean age of the patients was 54 years (range 30-77). Prior therapy included radiotherapy (13 cases), radical hysterectomy (11), and none (1). Fifteen (79%) of the 19 evaluable patients responded, including 6 with a complete response (CR) lasting over 15 months. Almost all the disease located in lung, liver, bone, and vulva showed a response. In particular, lesions confined to the lung had a 100% CR when the size of each tumor was under 2 cm in diameter even in the case of multiple metastasis. In contrast, 9 patients with pelvic disease had a 56% response with only 1 CR who had no previous radiotherapy. Such a poor response in the pelvic disease was considered to be due to vascularity reduced by prior radiotherapy. The important factors affecting the response to a new BOMP were found to be lesion size, prior radiotherapy, and the site of lesion. Patient age, performance status (PS), and the interval from a previous treatment to BOMP were not of significance with regard to response. The dose limiting factor was hematologic toxicities. Other toxicities including nausea, renal dysfunction, pulmonary fibrosis, and loss of hair were acceptable. Thus, the decrease in the PS of patients due to BOMP was minimal. It is suggested that this regimen will be useful as a neoadjuvant chemotherapy for advanced cervical cancer.

Graft-versus-host disease (GVHD) in leukemia patients following allogeneic bone marrow transplantation (BMT) has a lot of demerits but it also has a merit, namely graft-versus-leukemia effect. We reported the results of our recent trials on prevention, treatment and induction of GVHD, and prevention of viral infection after BMT. The results were as follows: 1) Twenty-four percent of patients who received prophylactic administration of cyclosporine and short term methotrexate still developed II degree-IV degree acute GVHD. 2) Patients with I degree or II degree acute GVHD showed good clinical courses. But, most patients with III degree GVHD gradually developed chronic GVHD. All patients with IV degree GVHD died of GVHD or infection. 3) Mizoribine and deoxyspergualin were effective for steroid-resistant GVHD. 4) Bestatin was administered to recipients who did not develop GVHD until day 30 after BMT. An interim report suggests that bestatin may induce chronic GVHD and suppress the relapse of leukemia. 5) Oral administration of gamma-globulin may prevent viral enteritis. Intravenous administration of anti-cytomegalovirus monoclonal antibody may prevent cytomegalovirus pneumonia.

A patient with FIGO stage IIIb adenocarcinoma of the uterine cervix (moderately differentiated, endocervical type) underwent an exploratory laparotomy because of a direct cancer invasion to the bladder wall, and then she was treated with consecutive intraarterial (IA) CDDP (10 mg/day) combined with continuous IA 5-FU (250 mg/day). Six weeks after, CR (complete response) was obtained by this IA chemotherapy (total dose; 5-FU: 10,500 mg, CDDP: 300 mg). Further 5-weeks-IA chemotherapy was added to keep the "CR" effect (final total dose; 5-FU: 19,250 mg, CDDP: 500 mg). The only toxic sign was a mild nausea. The patient's PS (performance status) was 0 (normal activity) and thereafter she could undergo a "curative" radical hysterectomy. The cancer invasion to the bladder wall observed at the first exploratory surgery completely disappeared histologically as well as macroscopically. In obtained material, small "viable" cancer focus was found in the cervical canal but the margin was free, and all nodes were negative. Postoperatively, the patient has receiving a continuous IA 5-FU (125 mg/day) for 13 months as a maintenance and she is free of disease (NED) with a normal activity (PS = 0). The present treatment modality is considered to be promising for advanced cervical adenocarcinoma having a poor prognosis due to its low sensitivity to radiotherapy.

A 37-year-old female with refractory asthma taking betamethasone orally (1 mg/d), showed a fever of 38.5 degrees C, productive cough and dyspnea. The chest X-ray demonstrated diffuse infiltration in the left lower lung field. The WBC count was 16,000/mm3 with 6% eosinophils. She was treated with intravenous drip infusion of antibiotics (Cefotiam 2 mg/d and Sisomicin 150 mg/d) for 2 weeks, and her symptoms and the chest X-ray findings improved. However, at the end of the therapy eosinophilia was noticed. Sixteen days after the completion of antibiotic therapy, she again experienced fever, cough and dyspnea. The chest X-ray again demonstrated diffuse infiltrations in the left lower lung field. The total IgE level, histamine and circulating immune complex titers were elevated. The WBC count was 14,700/mm3 with 34% eosinophils. Although a sputum culture yielded no organisms, many eosinophils were observed in the sputum. There were no clinical or laboratory findings compatible with allergic broncho-pulmonary aspergillosis. After the administration of oral prednisolone (40 mg/d), the patient showed rapid improvement with resolution of all symptoms and normalization of the IgE, histamine and circulating immune complex levels. The chest X-ray revealed marked regression of the pulmonary infiltrations. A microscopic examination of a transbronchial biopsy specimen demonstrated moderate eosinophilic infiltrations. It was compatible with the diagnosis of pulmonary infiltration with eosinophilia. Treatment was performed with prednisolone. The result of a lymphocyte stimulation test was positive for Cefotiam. An in vitro test was performed to evaluate the diagnosis of drug allergy in this case.(ABSTRACT TRUNCATED AT 250 WORDS)

TNF, IL-1, IFN-gamma and PGE2 secretion of peritoneal macrophage obtained by peritoneal washing at the first day after laparotomy from 19 patients with cervical cancer and 19 with ovarian cancer, who were treated with sizofiran (SPG) intramuscularly before laparotomy or with recombinant interferon gamma (rIFN) intraperitoneally at the day of laparotomy, were studied. Treatment with SPG and rIFN significantly increased the number and secretion of TNF, IL-1 and IFN-gamma (p less than 0.05) but not that of PGE2. A high correlation between secretion of TNF and IFN-gamma (r = 0.99, p less than 0.01) was observed. These data suggest that potent tumoricidal activity of peritoneal macrophage obtained from the patients with gynecological malignancies could be expected by the treatment with SPG and rIFN due to the increased secretion of TNF, IFN-gamma and IL-1 and inhibition of increased secretion of PGE2.

The dimethacrylates, EpDMA and BdDMA, which have a bisphenol type epoxy chain and butadiene chain in their main chains, respectively, were synthesized. The properties of the terpolymer composed of EpDMA, BdDMA and MMA monomers were examined. The monomer mixture of EpDMA, BdDMA and MMA was used as the liquid of denture base resin, and the properties of the cured resin were examined. The polymerization shrinkage of the terpolymer of EpDMA-BdDMA-MMA decreased with the increase in the EpDMA concentration in the cured resin, and the transverse strength and the elastic modulus were greatest at the BdDMA concentration of 0.3-1 vol%. The denture base resin produced using a monomer mixture as the liquid, the transverse strength and the impact strength showed the highest values of about 110 MPa and 14 KJ/m2, respectively, at the liquid composition of 10 vol% EpDMA, 1 vol% BdDMA and 89 vol% MMA.

Twenty nine patients with ovarian cancer of common epitherial origin who had no evidence of disease proved by computed tomography after the initial operation and chemotherapy were studied. The patients were randomized into two groups; (A) administration of UFT (1-(2-tetrahydrofuryl)-5-fluorouracil mixed with uracil) orally at a daily dose of 300 mg, 12 cases, (B) no further therapy, 17 cases. The therapeutic efficacy of UFT was assessed pathologically at the second look laparotomy (SLL). Plasma levels of 5-FU, tegafur and uracil were determined once a month to check whether patients intake UFT regularly or not. There were no significant difference in the mean age, in the distribution of numbers of patients in FIGO stage and histological cell type, in the mean total doses of CDDP and doxorubicin given at the initial chemotherapy [CDDP: (A) 352 +/- 152 mg, (B) 464 +/- 192 mg, doxorubicin: (A) 118 +/- 76 mg, (B) 119 +/- 92 mg] and in the duration between the initial operation and the SLL [(A) 484 +/- 154 days, (B) 414 +/- 274 days] between the two groups. The mean periods in the administration of UFT were 484.3 +/- 154 days. Recurrence was identified at the SLL in 1 case (8.3%) at paraaortic lymph nodes in (A) and 3 cases (17.6%) at the mesenterium, cul-de-sac and ascitic fluids in (B). No significant difference of recurrence ratio was observed between the two. Further long-term observation is required to assess the advantage of administration of UFT.

Of a total of 1,025 cases of radical hysterectomy for histological squamous cell carcinoma (543 stage I cases and 482 stage II cases), we examined 50 cases of recurrence of the carcinoma (4.9 percent; 24 stage I cases and 26 stage II cases) at the site of the vaginal stump. The percentage of recurrence at the site of the vaginal stump was significantly higher in stage I and stage II cases, in which metastases to the lymph nodes or vascular invasion was observed (p less than 0.01). The length of vagina excised during the radical hysterectomy was measured and its relationship to recurrence at the site of the vaginal stump was investigated. In stage I cases that did not exhibit metastases to the lymph nodes, the shortest vaginal length excised in cases with a positive recurrence at the site of the vaginal stump was 2.5 +/- 0.9 cm; the shortest vaginal length in cases with a negative recurrence at the site of the vaginal stump was 1.8 +/- 0.8 cm. A significant difference (p less than 0.05) was observed between them. Furthermore, in stage I cases with no metastases to the lymph nodes, one recurrence at the site of the vaginal stump was observed when the vaginal length excised was 3 cm. In stage I cases with metastases to the lymph nodes and in stage II cases, no significant difference was discovered between the length of vagina excised in cases with positive and those with negative recurrences of the carcinoma at the site of the vaginal stump.

Sixty-two patients with gynecological disease, who were treated with sizofiran (SPG) intramuscularly before laparotomy or with recombinant interferon gamma (IFN) intraperitoneally on the day of the laparotomy, were studied to investigate the change on the number and function of peritoneal macrophages (PM) obtained by peritoneal washing on the day and on the 1st and 4th days after the laparotomy. SPG significantly increased the number of PM by the 1st day, and IFN by the 4th day (p less than 0.05). However, IL-1 and IFN-gamma secretion by PM were not activated by SPG or IFN treatment, respectively. When patients were treated with these two agents simultaneously, the number of PM was significantly increased by both the 1st and the 4th day (p less than 0.05), and IL-1 and IFN-gamma secretion by PM were also significantly activated by the 1st day (p less than 0.05). These data suggest that SPG and IFN had a synergistic effect on increasing the number of PM and on activating the secretion of cytokines by PM, and that the priming with SPG played an important role in the activation of PM function by IFN.

Immunohistochemical study with various monoclonal antibodies to the mononuclear cell surface antigens was carried out on the regional lymph nodes in patients with cervical cancer to assess the augmentative effect of lentinan. Zero, 2, 4, or 6 mg of lentinan was administered i.v. one day prior to surgery to patients with cervical cancer (14 cases with FIGO stage 0 and 19 with FIGO stage Ib) and those with benign gynecologic tumors (8 cases with myoma uteri and 6 with ovarian tumor). Frozen sections of fresh pelvic lymph nodes obtained from these patients during surgery were stained by the ABC (avidin-biotin-peroxidase complex) method using several monoclonal antibodies to define the surface phenotype of mononuclear cells. The results were as follows: 1. Pelvic lymph nodes in patients with benign disease: In the absence of lentinan, lymphocytes stained with Leu 3a antibody were more numerous than those stained with Leu 2a, and both were observed mainly in the paracortical area (PC). The number of lymphocytes stained with Leu 4 antibody was practically equal to the sum of those stained with Leu 3a and Leu 2a. HLA-Dr positive lymphocytes were present in moderate numbers in PC and sinus. The above findings were not changed by the administration of lentinan. Cells stained with monoclonal antibodies including Leu 7, 11, M3, and IL-2 receptor (IL-2R) were very few or absent. 2. Pelvic lymph nodes in patients with cervical cancer receiving no lentinan: The findings obtained in these cases were much the same as those in patients with benign tumors.(ABSTRACT TRUNCATED AT 250 WORDS)