Biomedical subjects
Publications and source records attributed to S Ohtake.
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To investigate the proliferative characteristics of human bone marrow leukemic cells in vivo, we developed a new method using bromodeoxyuridine (BrdU) and its monoclonal antibody. Thirty minutes after a bolus BrdU infusion, a lst bone marrow aspiration (BMP) was performed to calculate the BrdU labeling index (BrdU-LI). Then, a 150-min continuous infusion of BrdU was started. Immediately after the infusion, a 2nd BMP was done to analyze the increasing rate of the BrdU-LI for 3 h. Each smear was stained by an immunohistochemical method. The BrdU-LI, the duration of S phase (Ts) and the cell cycle time (Tc) of leukemic cells from 13 previously untreated patients with acute leukemias were estimated. A mean value of 7.2% for BrdU-LI was obtained. Furthermore, mean values of 9.7 h and 152.5 h for Ts and Tc respectively were calculated. This method may prove to be useful in the in vivo cell cycle analysis of leukemias and other malignancies.
The authors administered recombinant human granulocyte colony-stimulating factor (rhG-CSF) to 16 patients with advanced non-Hodgkin's lymphoma treated with combination chemotherapy. Groups of three to five patients were treated with 50, 100, 200, and 400 micrograms/m2 per day of rhG-CSF by intravenous infusion for 14 days, beginning 3 days after chemotherapy. There was a strong linear relationship between the dose and the area under the curve over this dose range. The rhG-CSF was rapidly cleared from serum, with a mean half-life of 5.97 hours for the second phase (t1/2). In patients treated with a dose of more than 100 micrograms/m2 per day, the duration of neutropenia (P less than 0.01) and the duration of fever (P less than 0.05) were significantly decreased. The rhG-CSF was well tolerated and the only clinical observation that appeared relating to rhG-CSF administration was slight bone pain. This study strongly suggests that an optimum dose of rhG-CSF in patients after chemotherapy is 100 to 200 micrograms/m2. Our study shows that rhG-CSF is a clinically useful drug for patients treated with myelosuppressive chemotherapy.
We describe the clinical course of a 16 year old girl with aplastic anemia who was treated by syngeneic bone marrow transplantation. Engraftment was not obtained by simple infusion of bone marrow without immunosuppression. The patient received a high-dose cyclophosphamide and thoracoabdominal irradiation, followed by second marrow transplantation from the same donor. Incomplete but significant hematologic recovery was observed; however, marrow failure recurred 5 months after transplantation. Since donor and recipient pairs were genotypically identical, graft failure could not be attributed to immunological reactivity of recipient cells to donor non-HLA antigens. This case report implies that graft failure in some cases of aplastic anemia might be mediated by inhibitory cells resistant to cyclophosphamide and irradiation.
Silver staining of nucleolar organizer regions (NOR) was applied to air-dried peripheral and bone marrow smears of normal subjects and leukemic patients. Specimens were fixed in buffered acetone formalin. Even in smears kept for 2 years at room temperature, the stainability of Ag-NOR was well preserved. By dipping Giemsa-stained smears in 5% trichloracetic acid and then placing them in methanol for 5 minutes, the stain was leached out. After the dye had been removed, the smears were clearly stained by a Ag-NOR staining technique. The mean number of Ag-NOR per nucleus of mature granulocytes and mononuclear cells in normal peripheral bloods was 0.59 and 1.43 respectively. The mean number of Ag-NOR per nucleus of peripheral and bone marrow leukemic cells from patients with acute leukemia and chronic myelocytic leukemia in blastic crisis was 2.32 and 2.66 respectively. On the other hand, the mean number of Ag-NOR per nucleus of peripheral leukemic cells from patients with chronic lymphocytic leukemia was 1.48. These results suggest that acute leukemia cells possess a more active proliferating potential. The Ag-NOR staining technique is very simple and might be useful for investigation of hematologic cells.
We treated 14 patients with aplastic anemia (6 severe, 8 moderate) who did not respond to high dose methylprednisolone, antilymphocyte globulin, or anabolic steroid with cyclosporin (CyA) for more than 4 weeks. Four of them (29%) showed clinical improvement to transfusion-independence. The response rate of patients who received CyA more than 5 weeks was 50% (4 out of 8). The dose of CyA given to the 4 patients who improved after the therapy was 5 to 9 mg/kg/day. One patient needed 11 weeks until the first sign of response (increase of reticulocytes) appeared. In the other three patients, platelets increased first in response to CyA within 5 weeks. Side effects such as hypertricosis and gingival hyperplasia were frequently seen during the CyA therapy, but since they were not so severe or transient, almost all patients tolerated the therapy. These results indicate that CyA can be an efficacious drug for patients with refractory aplastic anemia. Long term treatment with a relatively low dose of CyA may be important for obtaining a high response rate.
The diagnostic potentiality of MR imaging for lung cancer was researched in 17 patients in evaluating local invasions based on surgical-histological evidence. Comparative reviewing with CT was also performed. MR imaging appeared to have an ability unique to portray malignant invasions somewhere such as in the hili or apices. On the other hand, there were also some diagnostic limitations of MR imaging in delineating the localized invasive changes. On the way of working up lung cancer, CT still may stand at the first choice as a radiographic staging procedure which provides the more detailed anatomic-pathologic informations. We consider that MR imaging is mandatory when CT and/or other modalities could'not obtain efficient results.
We established new approaches for CT guided selective pneumomediastinography; paravertebral, pretracheal and anterior mediastinal approaches. CT would seem to be useful method for assessing the invasion to the neighboring structures in the thoracic neoplasms. But scanty fat in mediastinum often interferes with correct evaluation of mediastinal structures in conventional CT. Pneumomediastinal CT with our methods overcomes the weak point and provides additional information to enable exact diagnosis. The feasibility and security of these methods were confirmed through applying to many cases. Based upon these results, selective pneumomediastinal CT would be considered to be advantageous and advisable on the CT diagnosis in thoracic imaging.
Overnight monitoring using pulse oximeter was performed on 10 patients with Duchenne muscular dystrophy (mean age, 22; mean %FVC, 26.6%; mean PaCO2, 54.1 Torr; mean PaO2 76.6 Torr). At the same time, spinal deformity and obesity were examined. In 4 patients, the measurement of the chest and abdominal wall movements were performed by using a respisomnograph. In 5 patients, nocturnal desaturation below 95% occurred despite normal daylight blood gas tension. In the other 5 patients with hypercapnea of over 50 Torr, nocturnal desaturation below 85% occurred, and 3 patients required oxygen supplementation treatment using a low concentration of oxygen. In 4 patients with hypercapnea over 50 Torr, cuirass-assisted respirators were used and they prevented mild nocturnal desaturation, but did not have much effect on severe nocturnal desaturation. Nocturnal desaturation was associated not only with hypopnea and hypoventilation, but with normal chest and abdominal wall movement using cuirass-assisted respirators. It seemed that desaturation with normal respiratory pattern can be attributed to ventilation-perfusion mismatching. The severity of the desaturation did not always correlate to the spinal deformity and the obesity.
A total of 40 patients with recurrent non-Hodgkin's lymphoma were treated with ABEP combination chemotherapy (aclarubicin, N4-behenoyl-1-beta-D-arabinofuranosylcytosine, etoposide, and prednisolone). A complete remission (CR) was achieved in 37.5% of the patients and partial remission, in 15.0%. The ABEP regimen proved to be effective in T-cell as well as B-cell lymphoma. It appears that the ABEP regimen may be partially non-cross-resistant with front-line doxorubicin-containing combinations. Survival for 39 months was achieved in 42.0% of the CR responders compared with 6.7% of partial responders (PRs) and nonresponders (NRs) (P less than 0.01). Disease-free survival for 45 months was seen in 66% of the CR patients. The ABEP regimen was effective in the treatment of patients with recurrent or refractory lymphoma, enabling hope for long-term survival in the majority of CR cases.
Thirty-three patients with complex lesions undergoing the Fontan operation needed either direct tricuspid closure (group 1, 14 patients) or atrial partitioning (group 2, 19 patients). In group 1, the tricuspid patch was sutured to the annulus leaving the coronary sinus draining to the systemic venous atrium. In group 2, atrial partitioning was accomplished with either a Dacron or a polytetrafluoroethylene patch, leaving the coronary sinus draining to the pulmonary venous atrium. Intraoperative distention of the left side was used to check for residual defects. In group 1, complete heart block developed in 5 patients (36%) and patch disruption, in 4 patients (29%). There were 3 late deaths (21%), which were due to sudden death, sepsis caused by Candida, and liver failure. In group 2, no patient had heart block, and patch disruption developed in 1 patient (5%). There was 1 early death (5%) and 2 late deaths (11%), which were due to sepsis caused by Candida and renal failure. Our experience suggests that atrial partitioning is a better approach than direct tricuspid patch closure in patients with complex lesions undergoing the Fontan operation.
Sixty infants with transposition of the great arteries and intact ventricular septum underwent primary surgical correction in the first 3 months of life. Twenty-three patients had a Mustard procedure (group 1) and 37 patients, an arterial switch operation (group 2). The mean age at the time of repair was 42 +/- 31 days for group 1 and 8 +/- 6 days for group 2 (p less than 0.001). The mean weight at the time of repair was 3.6 +/- 0.7 kg for group 1 and 3.4 +/- 0.5 kg for group 2 (p = not significant). Operative mortality was 8.7% (2/23) in group 1 and 8.1% (3/37) in group 2 (p = not significant). The incidence of arrhythmias in the early postoperative period was 39% (9/23) in group 1 and 11% (4/37) in group 2 (p less than 0.01). All patients were followed a mean of 4.8 +/- 2.4 years in group 1 and 2.6 +/- 1.4 years in group 2 (p less than 0.001). Postoperative catheterization has been performed in 86% (18/21) of group 1 operative survivors and 50% (17/34) of group 2 operative survivors. Ejection fraction of the systemic ventricle was 79% +/- 15% of predicted normal in group 1 and 98% +/- 6% in group 2 (p less than 0.005). The incidence of late arrhythmias was 57% (12/21) in group 1 and 3% (1/34) in group 2 (p less than 0.001). There have been 2 late deaths in group 1 and 1 late death in group 2 (p = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)
The adequacy of hepatic circulation in terms of oxygen supply-demand relation was assessed by measuring hepatic venous oxygen saturation (Shvo2) in patients. Among those with congenital cardiac lesions (n = 11), Shvo2 during the early postoperative period was markedly low as less than 20% in Fontan operation group (n = 5) with subsequent clinical findings of acute hepatic dysfunction. Significant correlations were found between Shvo2 values early after surgery and subsequent peak values in serum hepatic enzymes. Serum total bilirubin and prothrombin time started to deteriorate when Shvo2 became below 30%. Cardiac index, hepatic perfusion pressure and mixed venous oxygen saturation showed positive linear correlations with Shvo2, and central venous pressure (CVP) with an inverse relation. In chronic valvular disease (n = 28), those with NYHA class IV patients showed lower Shvo2 (average; 47.4%) at cardiac catheterization than the others (class-I; 66.4%, class-II; 63.9%, p less than 0.05). These results indicate that Shvo2 monitoring appears to be useful to assess the hepatic perfusion in terms of oxygen supply-demand relation in acute and chronic heart failure, and Shvo2 of 30% seems to be a critical level.
At Kanazawa University 28 patients with Hodgkin's disease were treated between 1975 and 1988. Ten patients underwent staging laparotomy by which we had to change the pathological stage in 3 patients because occult splenic lesions were detected histologically. Patients with early disease were treated mainly with radiotherapy (RT) and those with advanced disease received modified MOPP chemotherapy with or without RT. Twenty-six patients entered complete remission, and relapse occurred in 7 including 5 patients with stage III disease. Four patients died of the disease and 4 of other causes. The actuarial survival at 5 and 10 years were 80.1% and 47.1% respectively. The actuarial relapse free rate at 10 years was 65.8%. Fourteen patients are in good health after completion of treatment, and 9 healthy babies were born to 5 patients including 3 female patients. The goal of therapy in Hodgkin's disease is cure. Treatment strategy must be based on proper staging and consideration of iatrogenic morbidity such as sterility and second malignancy.
Two patients aged 2 months and 9 days with postoperative mediastinal infection were treated by continuous closed irrigation with 0.5% povidone-iodine solution. Satisfactory eradication was achieved in both two patients. Although serum iodine level was elevated as high as 7,610 micrograms/dl in the neonatal patient, no disturbances of the thyroid function and the acid-base balance were seen. The usefulness of continuous closed irrigation in the neonatal or infantile period was suggested.
The clinical data of 53 patients with Stage III-IV Hodgkin's disease collected from 9 institutions in Japan were analyzed for the efficacy of chemotherapy. CR rate (78%) and five-year relapse-free survival (RFS) rate (61%) were higher in the patients treated with VEPA/CHOP regimen than those in patients with VEMP/BONP or MOPP/C-MOPP regimen, although the difference was not statistically significant because of the small number of the patients. As to 14 patients treated with CHOP regimen, CR rate was 87% and RFS curve trend toward plateau at 67% after 2 years and 3 months from the initiation of chemotherapy. Salvage therapy with adriamycin-based combination chemotherapy achieved CRs in 9 of 14 (64%) patients who had been treated with VEMP, BONP, modified MOPP or C-MOPP regimen. The CHOP regimen was effective in the treatment of III-IV Hodgkin's disease but an alternative multidrug chemotherapy with ADM, CPM, VCR, BLM, etoposide and procarbazine is recommended for achieving a higher CR rate and a better RFS. Prospective study is needed to establish the standard chemotherapy for Hodgkin's disease in Japan.
A noninvasive and quantitative evaluation of pulmonary regurgitation (PR) using pulsed Doppler echocardiography (PDE) was performed in 25 patients with tetralogy of Fallot (TOF) after corrective surgery. Considering a possibility of the presence of the difference in regurgitant flow velocity in pulmonary artery, four sampling points for detecting the pulmonary regurgitant flow were designed as follows: point 0 was positioned at the right ventricular outflow tract; point 1, at the pulmonary annulus; point 2, at mid-portion of the pulmonary trunk; point 3, at bifurcation of the pulmonary artery. The values of maximum Doppler shift determined by analysing the sonograms recorded at point 1, 2 and 3 were examined in comparison with the grades of PR estimated by pulmonary arteriography and the results obtained were as follows. In a retrospective study in 18 patients with PR, the values of maximum Doppler shift were highest at point 1, and followed by point 2 and point 3 in order (p less than 0.005), indicating that the velocity gradient of regurgitant flow existed in the pulmonary artery. The values of maximum Doppler shift were highest in the group of PR grade III estimated by pulmonary arteriography, and followed by the group of PR grade II and grade I in order. At point 2, the group of grade III-PR showed significantly higher Doppler shift than the group of grade I-PR (p less than 0.05). Following above data, a new criteria for estimating the severity of PR by PDE according to the velocity gradient of regurgitant flow in the pulmonary artery was proposed. In a prospective study in a separate group of other 7 patients, the grade of PR estimated by PDE corresponded well with these of pulmonary arteriography, with a significant Spearman rank correlation coefficient (rs = 0.90, p less than 0.01). An experimental study using a dog with surgically induced PR of different grades confirmed the presence of higher Doppler shift in pulmonary artery corresponding to the grade of PR. These results indicated the usefulness of a newly proposed method evaluating PR by PDE applying a concept of Windkessel model for PR regurgitant flow.
The beneficial effects of a stable prostacyclin analogue (PGI2-A), OP 41483 against myocardial ischemic injury were experimentally and clinically evaluated. In 31P-NMR study, the preischemic treatment with PGI2-A prevented myocardial ATP depletion of rat hearts which were subjected to 20 min global ischemia. In patients with congenital heart disease, the PGI2-A of 300 ng/ml was added to the glucose-insulin-potassium cardioplegia (PGI2-group), and this group was compared to control group without PGI2-A in terms of postoperative maximal leakage of CPK-MB (maxCPK-MB). In patients under 1 yr or patients over 1 yr with aortic cross clamp time exceeded 120 min, the maxCPK-MB was significantly (p < 0.05) reduced as compared to the control. This stable PGI2 analogue has shown significant myocardial protective effects experimentally and also in clinical setting.