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Biomedical subjects

M Kitamura

Publications and source records attributed to M Kitamura.

At least 325 records · Page 18Linked to original sources

Twelve years' experience with the St. Jude Medical valve prosthesis.

Since July 1978, 1,284 patients have received the St. Jude Medical prosthesis (425 aortic, 636 mitral, and 223 double aortic-mitral), and the results in these patients were reviewed according to guidelines of the Society of Thoracic Surgeons. Follow-up was complete in 98%. Of 80 late deaths, 29% were valve related. The actuarial survival rate, including operative deaths, at 12 years was 81.7% and 87.1%, respectively, for aortic and mitral valve replacement, and it was 82.6% at 11 years after double valve replacement. All patients were anticoagulated with warfarin to maintain the thrombotest value between 10% and 25%, which is equivalent to between 2.8 and 1.6 times the control according to the international normalized ratio of the prothrombin time. The linearized rate of complication for aortic, mitral, and double valve replacement, respectively (expressed as the percent per patient-year), was as follows: structural deterioration, 0; non-structural dysfunction, 0.16, 0.30, and 0.20; valve thrombosis, 0.05, 0.09, and 0; thromboembolism, 1.35, 1.63, and 0.79; anticoagulant-related hemorrhage, 0.10, 0.18, and 0.10; and prosthetic valve endocarditis, 0.21, 0.06, and 0.20. Reoperation was performed in 16 patients. The freedom from reoperation rate at 12 years was 99.5% and 98.0% for aortic and mitral valve replacement, respectively, and it was 99.1% at 11 years for double valve replacement. Thus, during the 12-year follow-up in patient who received the St. Jude Medical prosthesis, the valve performed satisfactorily and with an acceptable risk of late complication even though patients were anticoagulated using a lower dose of warfarin.

Actuarial Analysis↗

The effect of selective growth hormone defect in the progression of glomerulosclerosis.

The role of endogenous growth hormone (GH) in the progression of glomerulosclerosis was examined in a new mutant strain of Sprague-Dawley (SD) rats with a selective GH gene defect. Fifteen spontaneous dwarf [GH(-)] rats and 10 SD rats underwent subtotal nephrectomy (Nx) or sham operation. Twelve weeks after Nx, the mean arterial pressure, glomerular filtration rate, urinary protein excretion rate, glomerular size, and frequency of glomerulosclerosis were examined. Marked elevation in mean arterial pressure was seen in both SD/Nx and GH(-)/Nx rats. In both strains, the glomerular filtration rate at 12 weeks after Nx was approximately 50% to 60% of that seen in the respective Sham-operated rat groups. The urinary protein excretion rate increased significantly only in the SD/Nx rats. The glomerular size, expressed as the ratio of glomerular volume to body weight, increased by 200% in the SD/Nx rats compared with the SD/Sham rats, in marked contrast to the 70% increase in the GH(-)/Nx rats compared with the GH(-) rats. The frequency of glomerulosclerosis in the GH(-)/Nx rats (1.0 +/- 0.5%) was significantly lower than that in the SD/Nx rats (16.7 +/- 2.8%). The frequency of glomerulosclerosis correlated with glomerular hypertrophy in both the SD and GH(-) rats (r = 0.88 and 0.67, respectively). These results show that the progression of glomerular sclerosis was markedly attenuated in the GH-defective rats. This attenuation of structural injury was correlated with a marked decrease in glomerular hypertrophy. These studies indicate that this specific growth regulatory peptide of endogenous origin plays an important determining role in the progression of glomerulosclerosis.

Analysis of Variance↗

Gene transfer of metalloproteinase transin induces aberrant behavior of cultured mesangial cells.

The aim of the present study is to clarify whether the cellular expression of a matrix-degrading metalloproteinase, transin, alters the behavior of cultured mesangial cells (MCs). The cDNA encoding rat transin was introduced into rat MCs and transcribed under the control of a Rous sarcoma virus promoter. The resulting transfectants were then investigated for cell shape, migration, proliferation, and expression of genes associated with matrix metabolism. Northern blot analysis routinely detected the transin transcript in two separate transfectants, MeTRN2 and MeTRN5. Transin expression was strong in MeTRN2, moderate in MeTRN5, but absent in mock transfectants. Immunoblot analysis revealed that these transin transfectants synthesized 59 and 62 kDa molecules, which correspond to transin gene products. Casein digestion assay detected enhanced proteolytic activity in MeTRN2 and MeTRN5. Microscopically, the transfected cells were somewhat elongated with accentuated margins compared with mock transfectants. [3H]-thymidine uptake studies revealed accelerated growth of the transfectants on a plastic substratum as well as within gel matrix. The migration of the transfectants into gel matrix was also significantly enhanced compared with that of mock transfectants. No obvious alteration, however, was found in transcripts of procollagen alpha 1(IV), laminin B2, or the metalloproteinase inhibitor TIMP. We hypothesize that the metalloproteinase transin has a potential for affecting the behavior of MCs and contributing to the pathogenesis of glomerular injury.

Animals↗

Progressive activity in latent prostate carcinoma defined by argyrophilic staining of the nucleolar organizer regions (AgNOR).

Argyrophilic staining of the nucleolar organizer regions (AgNOR) was studied in 30 cases of benign prostatic hyperplasias (BPH), 17 cases of latent prostate carcinomas, 50 cases of clinical carcinomas and seven cases of metastatic lesions from prostate carcinomas. The criteria for these comparisons were the number of positive-staining dots per nucleus, the area of the dots, and a relative score determined by multiplying the number of positive-staining dots in the nuclei by the areas of the dots. Overall, there were no significant differences in these three parameters between BPH and latent carcinomas. Among latent carcinomas, however, significantly higher AgNOR scores were observed for infiltrative lesions than for non-infiltrative lesions. AgNOR dot number, area and score increased as tumors became less differentiated, with no significant differences detected in metastatic versus non-metastatic carcinomas. These results suggest that some latent tumors are similar in biological behavior, such as cell proliferation, to clinical carcinoma.

Carcinoma↗

Neonatal thymectomy diminishes renal IgA deposition in IgA nephropathy-prone ddY mice.

To understand the role of thymus-derived T cells in the development of IgA nephropathy (IgAN), we performed neonatal thymectomies on ddY mice, in which this disease occurs spontaneously. Although these thymectomized mice developed a renal lesion closely resembling that typical of IgAN, the extent of their mesangial IgA deposition was significantly milder than in control sham-operated mice. The immunological mechanisms responsible for curbing this mesangial deposition of IgA were then analyzed. The percentage of splenic T cells and the magnitude of mitogenic responses both decreased markedly in thymectomized compared with control mice. These results suggested the hypofunction of thymus-derived T cells. However, serum IgA levels were almost identical in both groups. Furthermore, sera from both groups contained similar amounts of macromolecular IgA, of the type formerly eluted from the affected glomeruli of patients with IgAN. These results strongly indicate that thymus-derived T cells or their products determine the amount of IgA deposited in the kidneys of ddY mice.

Animals↗

Gene transfer into the rat renal glomerulus via a mesangial cell vector: site-specific delivery, in situ amplification, and sustained expression of an exogenous gene in vivo.

To evaluate the pathophysiological function of specific molecules in the renal glomerulus, selective, sustained, and modifiable expression of such molecules will be required. Towards achieving this end, we devised a gene transfer system using the glomerular mesangial cell as a vector for gene delivery. A reporter gene which encodes bacterial beta-galactosidase was introduced into cultured rat mesangial cells, and the stable transfectants were transferred into the rat kidney via the renal artery, leading to selective entrapment within the glomeruli. In the normal kidney, the reporter cells populated into 57 +/- 13% of glomeruli site specifically, and the expression of beta-galactosidase was sustained for 4 wk and declined thereafter. Within the glomerulus, some of the reporter cells remained in the glomerular capillaries, while others repopulated the mesangial area and, in part, extended their cytoplasmic processes toward the surrounding capillaries. When the cells were transferred into glomeruli subjected to transient mesangiolysis induced by monoclonal antibody 1-22-3, in situ expression of beta-galactosidase was amplified 7-12-fold, and the enhanced level of expression continued for up to 8 wk. The mesangial cell vector system thus achieves site-specific delivery of an exogenous gene into the glomerulus and is amenable to in situ amplification and sustained expression by preconditioning of the target site.

Animals↗

[Highly sensitive analytical procedure for methotrexate and its main metabolite 7-hydroxymethotrexate in serum by high-performance liquid chromatography].

Recently, methotrexate (MTX) low dose therapy (5-10 mg/m2) has been used for the treatment of patients with rheumatoid arthritis. Hence a practical and sensitive high-performance liquid chromatographic method for the determination of MTX and its main metabolite 7-hydroxymethotrexate (7-OH-MTX) in human serum has been studied. After deproteinization with perchloric acid followed by the addition of pH 5.0 acetate buffer, the serum sample was purified by solid-phase extraction on a Sep-Pak C18 cartridge. The analyte was chromatographed on a reversed-phase Inertsil ODS-2 column using a phosphate buffer-acetonitrile at pH 3.0 system as the mobile phase, and the effluent from the column was monitored at 303 nm. Gradient elution was employed to increase the sensitivity for 7-OH-MTX. A good linear relationship between peak height and concentration was found for the two compounds in the range 2.5 to 100 ng/ml of the human serum, and the detection limits were about 1 ng/ml for the two compounds. The day-to-day coefficients of variation assay were 2.3% (20 ng/ml) and 4.4% (100 ng/ml) for MTX and 4.6% (20 ng/ml) for 7-OH-MTX. The present method was successfully applied to the analysis of the serum after a single oral administration of MTX 2.5 mg tablet to male dogs. MTX was rapidly absorbed, reached to the maximal level at about 1.4 h and thereafter decreased monoexponentially with a half-life of about 1.4 h. A metabolite, 7-OH-MTX was not detected in the serum up to 24 h post dose.

Administration, Oral↗

[An autopsy study of the mode of cancer metastasis on the esophagectomied patients for esophageal cancer].

The records of autopsy on 43 patients underwent esophagectomy were evaluated retrospectively. Fifteen patients were performed palliative surgical treatment and 28 were curative, there were 41 men and 2 women in the series. The mean age at the first operation was 59.5 yr. The distribution of the primary lesions were 1 cervical, 40 thoracic (3 upper intra-thoracic, 28 middle intra-thoracic and 9 lower intra-thoracic) and 2 abdominal esophagus. There were 42 cases of squamous cell carcinoma (13 well differentiated types, 25 moderately differentiated types and 4 poorly differentiated types) and 1 adenosquamous cell carcinoma. Their stage classification were 0 for 2 patients, I for 1, III for 13 and IV for 27. In cases of palliative surgical treatment, the residual tumor were present on 6 cases in trachea or bronchus and 2 in aorta. Others were the rest of metastatic nodes in 3 cases, positive surgical margin in 3 and visceral metastasis and peritoneal dissemination in 1. At autopsy, 14 patients (93%) had distant organ metastases, 11 (73%) local recurrent tumor, 11 (73%) node metastases and 9 (60%) disseminations. In cases of curative surgical treatment, the first recurrent sites were as follows. Lymph node metastasis observed in 20 cases (71%), local recurrence in 9 cases (32%), distant organ metastases in 8 cases (28%) and disseminations in 5 cases (18%). While at autopsy, 24 patients (86%) had lymph node metastases, 20 (71%) distant organ metastases, 15 (54%) local recurrent tumors and 11 (39%) disseminations. On 10 cases whose first recurrent site was observed only at lymph node, 9 cases (90%) had distant organ metastases at autopsy. In both cases of palliative surgical treatment and of curative surgical treatment, the most dominant metastatic site at autopsy was distant organ metastasis. Therefore, in the future, distant organ metastasis must be an important target for esophageal cancer treatment.

Adult↗

[Intrathoracic half-working heart and lung transplantation in the rat].

A new technique of intrathoracic half-working heart-lung transplantation in the rat was established. Donor heart-left lung graft was transplanted into left hemithorax of the recipient with aorta-aorta, bronchus-bronchus and superior vena cava (SVC)-SVC anastomoses, and the recipient's descending aorta proximal to the anastomosis was ligated. Five isografts (Lewis-Lewis) showed excellent cardiopulmonary function 4 weeks after transplantation. In 11 allografts (DA-Lewis), 5 rats without immunosuppression survived in 4-6 postoperative days and 6 rats with cyclosporine 10 mg/kg/day were alive during 8-14 days after operation. Nine of 11 allografts demonstrated moderate to severe (ISHLT grade 3-4) acute rejection and the grade of lung rejection was higher than that of heart rejection in 4 of 9 allografts.

Acute Disease↗

[Effects and problems of intraarterial noradrenaline-induced hypertensive chemotherapy for liver metastasis of gastric cancer].

Intraarterial noradrenaline-induced hypertensive chemotherapy (NA-IHC) was performed on eight patients with liver metastasis of gastric cancer (3 synchronous and 5 metachronous). Mitomycin C was injected via the indwelling catheter placed in the proper hepatic artery, when the mean systolic blood pressure rose to 50 percent above the level in the untreated state by intravenous administration of noradrenaline. As the result, the response rate was 62.5% (CR: 1, PR: 4, NC: 2, PD: 1) and the 50% survival period was 792 days. On the other hand, another hematological metastasis developed in two cases in which liver metastases were effectively controlled. These results indicated both the effectiveness and the limits of NA-IHC as loco-regional chemotherapy. Therefore, we concluded that not only NA-IHC but also another systemic chemotherapy was necessary to treat the patient with liver metastasis of gastric cancer.

Aged↗

[Evaluation of intraperitoneal chemotherapy using CDDP combined with MMC in gastric carcinomatous peritonitis].

Based on the experimental studies using Meth A and L 1210 transplantable mouse, which indicated that simultaneous combined administration of MMC and CDDP prolonged life span more significantly than individual administration, clinical application was performed on 14 cases with carcinomatous peritonitis in gastric cancer. One hundred mg of CDDP was administered before the closure of abdomen and drainage tubes were opened 2 hours later. Then, repeated administration of 10 mg/body of MMC and 40-50 mg/body of CDDP was continued once a month via the drug delivery system. Negative change of cytology was observed in seven out of 14 cases, and the prognosis of these patients was better than in the unchanged cytology group. Side effects such as severe gastro-intestinal symptoms and bone marrow toxicities were not recognized. Further studies should be done to confirm the efficacy of the intraperitoneal chemotherapy for carcinomatous peritonitis.

Animals↗

[Seventy coronary reoperations: indication and results].

Seventy consecutive patients undergoing reoperative coronary artery bypass grafting (re-CABG) were reviewed to determine operative and late results, and indications of re-CABG. There was no operative death (within 30 days after re-CABG) but 3 (4.3%) hospital deaths in patients with emergency re-CABG. Although graft patency rate was acceptable (92.5%), the rate of complete revascularization was only 70%. Including non-cardiac death, the actuarial survival rate at 8 years was 88.2%, and event free rate including all deaths, the third time CABG, PTCA and myocardial infarction was 78.4% at 8 years. At re-CABG, no old arterial grafts and only 4.7% (2/43) of the old saphenous vein grafts to the left anterior descending artery (LAD) were patent without stenosis. Success rate of PTCA was 90.9% in the saphenous vein graft and 95.2% in the internal thoracic artery graft. Restenosis rate was significantly higher in the saphenous vein graft (55%) than the arterial graft (10%) (p < 0.001), and restenosis rate of repeat PTCA to the saphenous vein graft was 100%. In conclusion, re-CABG should be mainly indicated to the patients with persistent symptom and diseased grafts to the LAD, and PTCA to the old saphenous vein graft should be limited to once to avoid acute deterioration requiring emergency re-CABG.

Adult↗

[Long-term results after cardiac valve replacement: 16 years follow-up of 190 patients].

According to STS/AATS guidelines 1988, we compared the long-term results after cardiac valve replacement (ReAVR 26, ReMVR 127, ReDVR 35, ReTVR 2, total 190 patients) with those after initial valve replacement (AVR 760, MVR 1, 001, DVR 431, TVR 22, total 2,214 patients). Actuarial survival (AS), reoperation free (RF) and freedom from all valve-related events (EF) at the 10th postoperative year were 74.6%, 100%, 70.1% after ReAVR, 84.2%. 97.8%, 75.8% after AVR, 82.9%, 91.4%, 75.8% after ReMVR, 86.5%, 91.7%, 70.7% after MVR. 78.4%, 92.9%, 63.2% after ReDVR, 82.8%, 95.6%, 73.8% after DVR, respectively. There was no significant difference of AS, RF and EF between ReVR and initial VR in any valve position. These results justify our current strategy of cardiac valve re-replacement.

Adolescent↗

[Relation between surgical outcome and preoperative end-systolic volume of the left ventricle in patients with regurgitant valvular heart disease].

The relation between the end-systolic volume index of the left ventricle (ESVI (ml/m2)) and the early and late results after valve replacement were reviewed in 249 patients with pure aortic regurgitation (AR) and 189 patients with pure mitral regurgitation (MR). The patients with AR were classified into 4 groups (A1-A4) and those with MR were classified into 3 groups (M1-M3) according to the ESVI. The ESVI, the number of patients (No of P), early mortality rate (EM) and the actuarial survival rate at 12 years after valve replacement (AS at 12 yr) in each group are shown in the following Table. [table: see text] The actuarial survival rate at 12 years after operation in A1 and A2 were significantly lower than that in A3 and A4. In 57% of the late deaths in A1 and A2 patients, the cause of the death was thought to be rhythm disturbance. In contrast, there were no differences in late survival among the three groups with MR (M1, M2 and M3). The minor axis of the left ventricle at end-diastole and at end-systole (Dd and Ds) and shortening fraction of the left minor axis (FS), evaluated by echocardiography, were normalized early after the operation in A1 patients only. The Dd, Ds and FS in A2 and A3 returned to normal late after the operation. However, in A4, these parameters still remained abnormal. Thus, patients with a deteriorated left ventricle can survive the operation. However, the long-term results in patients with AR with ESVI more than 150 ml/m2 were unsatisfactory.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve Insufficiency↗

An evaluation of symptoms and performance status in patients after esophagectomy for esophageal cancer from the viewpoint of the patient.

We used a questionnaire method to investigate the complaints and the life conditions of 81 patients after esophagectomy for esophageal cancer. Patients were separated into three groups according to their follow-up time: less than 2 years, more than 2 years but less than 5 years, and more than 5 years after surgery. The distribution of complaints was similar regardless of the time elapsed since surgery. Only 22% of all patients had no complaints. Abdominal fullness and stenotic sensation were the major complaints. Body weight was unstable for 2 years following surgery, but subsequently stabilized. The content of meals, volume of meals, and Performance Status (PS) did not differ significantly among the groups and were indicative of satisfactory recovery. Our results suggest that in contrast to other surgeries, postoperative symptoms persist in esophagectomyed patients with long survival and that about half of the cases whose follow-up time was less than 2 years have unstable body weight.

Adult↗

[Sarcoidosis of the liver and spleen in Japan].

Although liver and/or spleen sarcoidosis usually shows no symptoms and subtle elevated levels of liver enzymes, diagnostic image scanning methods (abdominal ultrasonic scan, computed tomographic scan, magnetic resonance image, and Ga and Tc scintiscan) can easily detect the lesion. Laparoscopy unveils isolated scattered sarcoid nodules on the surface of the liver and/or spleen and biopsied specimen reveal a non-caseating epithelioid granuloma containing multinucleated giant cells especially in the portal area. Sometimes it is required to differentiate liver and/or spleen sarcoidosis from hepatic tuberculosis, primary biliary cirrhosis or malignant lymphoma. In severe cases, corticosteroid treatment is necessary. Prognosis is usually good, but may be poor in some cases.

Diagnosis, Differential↗