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Biomedical subjects

M Tobe

Publications and source records attributed to M Tobe.

At least 37 records · Page 2Linked to original sources

[Long-term results of closed mitral commissurotomy--comparative study of closed mitral commissurotomy (CMC), open mitral commissurotomy (OMC) and mitral valve replacement (MVR)].

As the technique of open heart surgery has improved, CMC has been abandoned in favor of OMC and MVR. We evaluated and compared the results of CMC, OMC and MVR. METHOD. Between 1965 and 1978, 141 patients with mitral stenosis (MS) underwent CMC, and late follow-up obtained in 117 (83%) of them (CMC group). Between 1980 and 1989, 72 patients and 37 patients underwent OMC (OMC group) and MVR (MVR group), respectively. Cumulative follow-up periods were 1982, 632 and 200 patient-years in the CMC, OMC and MVR groups, respectively. RESULTS. (1) Survival rate; In the CMC group there were 2 operative deaths due to severe mitral regurgitation (MR). There were 17 late deaths, due to reoperations in 4 patients, cerebral infarction in 4 patients, congestive heart failure in 3 patients, myocardial infarction in 2 patients and unknown causes in 4 patients. The survival rate was 95%, 91% and 86% at 5, 10 and 15 years, respectively, in the CMC group. In the OMC and MVR groups there was no death. (2) The event free rate was 89%, 79% and 58% at 5, 10 and 15 years, respectively, in the CMC group, 97% and 97% at 5 and 10 years in the OMC group, and 95% and 90% at 4 and 5 years in the MVR group. (3) Reoperations; In the CMC group of 40 patients (34%) required reoperations in an average of 10.4 years after the initial operation, due to re-MS in 22 patients, MR in 10 patients and MRS in the 8 patients. Reoperative findings consisted of clefts in the mitral leaflets in 7 patients. There were pulmonary hypertension in 15 patients and tricuspid regurgitation in 22 patients. Fourteen patients underwent tricuspid anuloplasty and one patient underwent a tricuspid valve replacement. In the OMC group one patient required a reoperation due to MR; in the MVR group one patient required a reoperation due to a thrombosed valve. CONCLUSION. In the CMC group the survival rate and the event free rate were lower, and the rate of reoperation was higher than in the other two groups.

Adult

Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (OECD): familiarization using cyclophosphamide.

A familiarization study was conducted on the "Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (ReproTox)" proposed by the OECD. Cyclophosphamide (CP) at doses of 6.7, 4.5, 3, 2, and 0 mg/kg body wt was given daily by gavage to groups of 12 male and 12 female Sprague-Dawley rats. As a result, anemia and leukopenia were evident in treated males. The absolute and relative thymus and spleen weights were decreased in treated rats. Histopathologically, atrophy of the thymus, spleen, and bone marrow was observed. With respect to the reproductive/developmental toxicity, dose-dependent increases in postimplantation loss of fetuses and postnatal death were found in dams given CP. The body weight of pups treated with CP was significantly lowered in a dose-related manner. Thus the results demonstrated most of the known toxicological properties of CP, except the adverse effects on spermatogenesis and fertility. Therefore ReproTox can be considered as a useful screening test for assessing repeat dose and reproductive/developmental toxicity of existing chemicals of high production volume.

Animals

Toxicities of microencapsulated tribromomethane, dibromochloromethane and bromodichloromethane administered in the diet to Wistar rats for one month.

The gelatin-starch syrup microencapsulation method was applied to subacute toxicity studies of tribromomethane (TBM), dibromochloromethane (DBCM) and bromodichloromethane (BDCM). Groups of Wistar rats (7 males and 7 females) both sexes were given diet containing microcapsules of each of these trihalomethanes (THMs) at the following concentrations: TBM, 0.068, 0.204 and 0.612% in males, and 0.072, 0.217 and 0.651% in females; DBCM, 0.020, 0.062 and 0.185% in males, and 0.038, 0.113 and 0.338% in females; BDCM, 0.024, 0.072 and 0.215% in males, and 0.024, 0.076 and 0.227% in females. Suppression of body weight gain was seen in each high-dose males fed TBM or BDCM and females fed DBCM or BDCM. Histopathologically, hepatic lesions such as vacuolization and swelling of liver cells were significantly noted in both sexes of all groups fed TBM, in both sexes of the middle- and high-dose groups fed DBCM, and in males of the high-dose group and in females of the middle- and high-dose groups fed BDCM. In addition, single cell necroses were observed in males and females fed DBCM and in males fed BDCM. Hepatic cord abnormalities were also noted in males of the high-dose group fed BDCM. Although no increases in serum transaminase activities (ASAT, ALAT) were evident in either sex fed any of the THMs, decreases in triglyceride content, cholinesterase and lactate dehydrogenase activity were observed. Renal lesions reported to occur in gavage studies were not found in the present feeding study. Lowest-observed-adverse-effect-level (LOAEL) of TBM and no-observed-adverse-effect-level (NOAEL) of DBCM and BDCM were determined to be 56.4 mg/kg, 18.3 mg/kg and 20.6 mg/kg, respectively, under the present experimental conditions.

Administration, Oral

Toxicity studies of a synthetic antioxidant, 2,2'-methylenebis (4-ethyl-6-tert-butylphenol) in rats. 1. Acute and subchronic toxicity.

The acute and subchronic toxicity studies on 2,2'-methylenebis (4-ethyl-6-tert-butylphenol) (MBEBP) were conducted using male and female Wistar rats. In acute toxicity test, the LD50 values were estimated to be greater than 10 g/kg BW by oral and intraperitoneal administration in each sex. In subchronic toxicity test, groups of 10 rats of each sex were fed a diet containing 0.2, 1.0 or 5.0% of MBEBP and examined at 4 and 12 weeks. Body weight gain was significantly depressed at doses of 1.0 and 5.0% in both sexes, but the depression in the 1.0% group was severer than that in the 5.0% group in males. Hematological analysis showed slight but significant decrease of hemoglobin in the 1.0 and 5.0% groups of both sexes. Urine analysis showed no remarkable changes in all treated rats of both sexes. In biochemical analysis of serum, decrease of triglyceride level and cholinesterase activity, and increase of amylase activity were observed in treated rats. Histopathologically, testicular atrophy and decrease of spermatogenesis were observed in male rats fed 1.0 or 5.0% MBEBP for 4 and 12 weeks and vacuolization of parathyroid gland cells was observed in female rats fed 1.0 and 5.0% MBEBP for 12 weeks. In subchronic test, the lowest observable adverse effect levels for MBEBP toxicity were estimated to be 171 mg/kg BW/day in male rats and 180 mg/kg BW/day in female rats.

Administration, Oral

Chronic toxicity of microencapsulated bromodichloromethane administered in the diet to Wistar rats.

A chronic feeding study was carried out in Wistar rats using microencapsulated bromodichloromethane. The test substance was administered in the diet at doses of 0, 0.014, 0.055 and 0.22% for 24 months. Rats were sacrificed after 6, 12, 18 and 24 months of continuous dosing. The results showed a suppression of body weight gain in the 0.22% group for both males and females. Dose related changes were clearly observed in the liver with histopathological findings including fatty degeneration in the 0.014% or higher dose male groups, and fatty degeneration and granuloma in the 0.055 and 0.22% group females, as well as bile duct proliferation and cholangiofibrosis in the 0.22% group for both males and females. No significant differences in incidences or numbers of neoplastic changes were seen between control and any of the treatment groups. There were no dose-related non-neoplastic lesions in the kidneys of either sex. Lowest-observed-adverse-effect-level was determined to be 6.1 mg/kg/day under the present experimental conditions.

Animal Feed

[Selection of graft materials in case of emergency coronary bypass surgery following failed angioplasty].

The clinical characteristics of selection of graft materials were analysed for patients undergoing emergency coronary artery bypass surgery (CABG) following failed coronary angioplasty (PTCA). Ten emergency CABGs were performed from January 1983 to December 1991. Perioperative variables and follow-up were compared to 18 patients undergoing elective CABG after PTCA. The emergency group had shorter operative time (p less than 0.01) and shorter bypass time (p less than 0.05). Moreover the emergency group had decreased use of the internal thoracic artery (ITA) (40% vs 94.4%, p less than 0.01). There was no use of bilateral ITAs in the emergency group. There was not significant difference in hospital mortality and medium term follow-up between two groups. In conclusion, emergency CABG carries a significantly less use of ITA graft than elective CABG although ITAs are superior to SVGs about long term patency rate. So it is desirable that arterial graft should be used under an appropriate selection at emergency operation.

Aged

[Surgical repair of discrete subaortic stenosis complicated with prosthetic valve endocarditis--a case report].

A 46-year-old man was referred to our hospital because of prosthetic valve regurgitation. Eight years previously he had undergone aortic valve replacement because of aortic regurgitation due to infective endocarditis. At reoperation, we found prosthetic valve endocarditis and discrete subaortic stenosis. The obstructing fibrous tissue was resected and the aortic valve was replaced. Because discrete subaortic stenosis is usually located just below the aortic valve, the aortic valve cusps are liable to become thickened by the jet through the discrete stenosis and thus are vulnerable to infective endocarditis. It is pointed out that care must be taken not to overlook discrete subaortic stenosis in the presence of other associated cardiac disorders.

Aortic Valve

[A case of reoperation of coarctation of the aorta 13 years after corrective surgery of coarctation of the aorta, ventricular septal defect and pulmonary hypertension in infancy].

A 13-year-old boy underwent corrective surgery of CoA + VSD + PH at 50-day. Vascular murmur and hypertension was present so that he was admitted to our hospital. Systemic pressure was 164/106 mmHg (right arm) and systolic blood pressure at right leg was 70 mmHg. The systolic pressure gradient was 94 mmHg. The intracardiac pressure was within normal limit and there was no shunt. And the stenosis of descending aorta was present at the distal of subclavian branch and that pressure gradient was 76 mmHg. The diagnosis was established recurrent coarctation and operation was performed. The recurrent coarctation was 8 mm in diameter and longitudinal incision was made and woven Dacron patch aortoplasty was done. Aortic cross clamping time was 43 minutes. Postoperative clinical course was smooth. At 4 weeks after aortography was performed and no appreciable stenosis of the descending aorta was revealed. The pressure gradient decreased from 76 mmHg to 11 mmHg.

Adolescent

Segmental mediolytic arteritis. Clinicopathologic study and three-dimensional analysis.

We describe the first recorded case of segmental mediolytic arteritis (SMA) in Japan. A 71-year-old Japanese woman developed sudden abdominal pain and went into shock during hospitalization for treatment of valvular heart disease. Laparotomy revealed a ruptured pseudoaneurysm of the left gastric artery. Histological examination of the resected artery revealed multiple extensive areas of the dilated wall where the media had partially or totally disappeared with or without the intima. These features were typical of those described previously for SMA (1,2). Three-dimensional analysis of the arterial lesions revealed that the residual media formed branches and cavities down the long axis of the artery, indicating that the major cause of the medial disappearance was arterial dissection. Three months later, the patient died of sepsis. Autopsy revealed pseudoaneurysm formation at three different locations in the splenic artery. Histologically, these pseudoaneurysms showed destructive changes in the arterial wall similar to those described above, with organization and thrombosis, and were considered to be the end-stage lesion of SMA. This case is considered to be the fifth adult case of SMA in the literature and the first one showing chronic changes.

Aged

[A surgically treated case of acute pulmonary embolism owing to deep vein thrombosis of the leg mainly caused by uterine myoma].

A 49-year-old woman with deep vein thrombosis of the left leg suddenly complained of slight dyspnea during her hospitalization. Enhanced chest CT and pulmonary arterial DSA revealed pulmonary emboli, while phlebography of the left leg and lower abdominal CT showed a uterine myoma compressing the left external iliac vein, which was regarded as a chief cause of deep vein thrombosis of the left leg. The patient became dyspneic severely with a rapid increase of pulmonary arterial pressure and a decrease of arterial oxygen pressure. Therefore, pulmonary embolectomy and deep vein thrombectomy of the left leg and pelvis was performed using a cardiopulmonary bypass. Hysterectomy was also performed after weaning the bypass. The postoperative course was uneventful without recurrence of pulmonary embolism. This was a very rare case of pulmonary embolism, because, as far as we investigated, no literature has reported deep vein thrombosis of the leg caused by uterine myoma. We emphasize the availability of the enhanced CT for diagnosis of pulmonary embolism.

Acute Disease

Carcinogenic effects of bis(2,3-dibromopropyl)-phosphate in Wistar rats.

Four groups of 40 Wistar rats of each sex per dose level were fed diets containing 0, 80, 400 or 2000 ppm of the magnesium salt of bis(2,3-dibromopropyl)phosphate (Bis-BP) for 24 months. A high incidence of tumours was induced, in both sexes, in the digestive system. Tumours included papillomas and adenocarcinomas of the tongue, oesophagus and forestomach, adenocarcinomas of the intestine and hepatocellular adenomas (neoplastic nodules) and carcinomas. Pre-terminal mortalities were associated with an increased incidence of forestomach papillomas in both sexes, adenocarcinomas of the small intestine in male rats and increased incidence of hepatocellular carcinomas in females. The data suggest that Bis-BP is a more potent proximate carcinogen than tris-(2,3-dibromopropyl)phosphate (Tris-BP).

Animals

[A study on the usefulness of the OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (ReproTox)].

We studied the usefulness of the OECD combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (ReproTox) using cyclophosphamide (CP), which is well known for its toxicological properties. CP was given daily by gavage to groups of 12 male and 12 female 8-week-old Sprague-Dawley rats at doses of 0, 2, 3, 4.5 or 6.7 mg/kg. Significant decreases in body weight and food consumption were observed in males given 6.7 mg/kg and in all treated females. One, 3 and 12 females died during pregnancy in the groups given 3, 4.5 and 6.7 mg/kg, respectively. In males 2 died in the 6.7 mg/kg group. Leukopenia and anemia were evident in treated males. The thymus and spleen weights were significantly decreased in treated rats. Histopathologically, atrophy of the thymus, spleen and bone marrow was observed. With respect to the reproductive/developmental toxicity, dose-dependent increases in postimplantation loss and postnatal death of pups were found in treated dams. The body weight of pups from treated dams was significantly lowered. Thus, most of the known toxicological properties of CP regarding systemic toxicity and reproductive/developmental toxicity were clearly demonstrated in this study. Therefore ReproTox can be considered a useful screening test for assessing repeat dose and reproductive/developmental toxicity of existing chemicals of high production volume, although teratogenic potential and adverse effects on spermatogenesis and fertility were not detected under the present experimental conditions.

Administration, Oral

[Combined chronic toxicity/carcinogenicity test of tris(2-chloroethyl)phosphate (TCEP) applied to female mouse skin].

Tris(2-chloroethyl)phosphate (TCEP), a widely used flame retardant, was tested for its skin chronic toxicity/carcinogenicity using female Slc: ddY mice. TCEP (5 and 50%) dissolved in ethanol was applied to the shaved skin twice a week for 79 weeks. The control group received ethanol under similar condition. In addition, 5 animals in each group were killed at 6 and 12 months and used for the chronic toxicity study. In body weight, food consumption and survival rate, there was no significant difference between the control and treated groups. Spleen weight was decreased in the 50% group. No significant difference in the incidence of tumors and other non-neoplastic lesions of the skin and other organs was found between the control and treated groups. The results indicate that under the conditions of the present study, TCEP has no carcinogenicity and toxicity for the skin.

Administration, Topical

[Acute and subacute toxicity studies of Bis(2,3-dibromopropyl) phosphate magnesium in rat].

Acute and subacute oral toxicity tests of Bis(2,3-dibromopropyl) phosphate magnesium (Bis-BP.Mg) were carried out in Wistar rats. In the acute toxicity test, Bis-BP.Mg suspended in arabic gum was administered orally to a group consisting of 10 male and 10 female rats, and they were observed for 14 days. LD50 values of male and female rats were 283 (253 approximately 314) mg/kg and 261 (219 approximately 310) mg/kg, respectively. As toxic symptoms, eyelid closure, crouching, shivering and staggering gait were observed in the treated groups of both sexes. In gross findings, hypertrophy, discoloration and necrotic change of the liver, and hypertrophy and discoloration of the kidney were observed in the treated groups. In histopathological examination, necrosis, desquamation, large nuclei formation of the tubular epithelium, and tubular dilatation of the kidney and necrosis of the liver cells were observed in the treated groups. In the subacute toxicity test, groups of rats consisting of 5 males and 5 females were fed a commercial diet containing 0, 30, 100, 300 and 1000 ppm Bis-BP.Mg for 45 days. In body weight and food consumption, there were no significant difference between the control and treated groups. Significant increases were observed in the liver and kidney weights of male rats fed 1000 ppm Bis-BP.Mg. Histopathologically, desquamation, swelling, and large nuclei formation of the tubular epithelium and tubular dilatation of the kidney were observed, but they were much less frequent than those in the acute toxicity test. It was concluded that Bis-BP.Mg has apparent renal toxicity.

Administration, Oral

A simple method for screening assessment of acute toxicity of chemicals.

We proposed a simple method for screening assessment of acute oral and dermal toxicity using only three rats and mice of each sex at each dose level. Animals were first treated with chemicals at a dose of 2000 mg/kg and were carefully observed for compound-related morbidity and mortality. If none of the animals died, the following toxicity tests were suspended. If some of the animals died, toxicity tests at doses of 200 and 20 mg/kg were performed. The approximate LD50 values calculated by this method showed little difference between two separate laboratories and were in good agreement with LD50 values reported in the literature. Our toxicological data also showed that LD50 values were about 2-2.5 times the MNLD (maximum non lethal dose) in acute oral and dermal toxicity. This meant that a chemical could be regarded as having an LD50 of about 4000 mg/kg or higher when there was no mortality at the dose of 2000 mg/kg. A chemical with such low toxicity would not require further testing for lethal effects. Therefore, this simple method combining the fixed-dose procedure with the limit test is suitable for determination of approximate LD50 values of chemicals and for screening for necessity for classical full LD50 test using many animals.

Ammonium Sulfate

[Tricuspid annuloplasty and right ventricular function in mitral valve disease].

From 1985 to 1987, we examined relationship between the lesion of tricuspid valve and right ventricular function in 31 patients (male: 9, female: 22) with mitral valve disease. The median age at operation was 52 years (range 37-69 years). Group I consisted of 17 patients (MS: 10, MSR: 5, MR: 2) accompanied with tricuspid regurgitation (TR) and Group II 14 patients (MS: 12, MSR: 2) without TR. In all cases of Group I tricuspid annuloplasty (TAP) were performed correctly. De Vega methods were done in 12 cases and Carpentier rings were used in 5 cases. Cardiac catheterization was done before and after operation. And right ventricular volume was measured by right ventricular angiography. In both groups pulmonary capillary wedge pressure, pulmonary artery pressure and cardiac index were improved postoperatively. Pulmonary artery resistance (PAR) and total pulmonary resistance (TPR) in Group I were significantly higher before operation but there were no difference between two groups postoperatively. Right ventricular end-diastolic volume index (RVEDVI) and right ventricular end-systolic volume index (RVESVI) in Group I were significantly improved postoperatively, but in Group II these were within normal range both pre- and postoperatively. Preoperative PAR was correlated inversely with postoperative right ventricular ejection fraction (RVEF). It means that patients with severe pulmonary vascular lesion had postoperative lower right ventricular function. In both groups, RVESVI was in inverse correlation with RVEF pre- and postoperatively. In both groups, there was an inverse correlation between the per cent change of RVESVI and that of RVEF. This means that RVESVI influenced right ventricular pump function.

Adult

[Evaluation of the thromboexclusion technique for thoracic aortic aneurysms].

From 1981 to 1987 most of DeBakey III type dissecting aneurysms and a part of descending aortic aneurysms were treated by thromboexclusion technique. The effects of the operation by thromboexclusion technique on the patients were compared with those of the operation by temporary bypass technique. Blood loss during an operation was smaller and blood pressure during an operation was more stable in the thromboexclusion technique group, although the difference was not statistically significant. Furthermore, no paraplegia was observed in the thromboexclusion technique group. The respiratory support period was longer and the number of patients with postoperative myocardial injury was greater in the thromboexclusion technique group, although the difference was not statistically significant. Ten patients treated by thromboexclusion techniques were examined by computed tomography. In 7 out of 10 patients (70%), thrombosis occurred in the false lumen of dissecting aneurysm or in the aneurysmal lumen of descending aortic aneurysm. When only the patients without the leakage of blood into the aneurysm through the permanent aortic clamp were examined, thrombosis was observed in 100% of them. Even though the blood flow was reversed, thromboexclusion technique did not have a bad effect on renal function in the long-term. Postoperatively, however, progressive hypertrophy of the left ventricle was recognized, and furthermore, an injury to the aortic wall caused by permanent aortic clamp was observed at an autopsy. This suggests that further long-term follow-up of patients treated by thromboexclusion technique is necessary.

Aged

Chronic toxicity study on formaldehyde administered orally to rats.

Groups of 20 male and 20 female Wistar rats were given formaldehyde solution in their drinking water at concentrations of 0.50, 0.10, 0.02 and 0% for 24 months. Significant decreases in body weight and food and water intake were observed in the 0.50% group of both sexes and all rats in this group died by 24 months. Various non-neoplastic lesions were observed in rats, mostly in the 0.50% group. In this group, erosions and/or ulcers were evident in both the forestomach and glandular stomach. In the forestomach, squamous cell hyperplasia with or without hyperkeratosis and downward growth of basal cells were observed. Glandular hyperplasia of the fundic mucosa was noted along the limiting ridge. A few of such changes of the upper GI tract were seen in the 0.10% group. No toxicological abnormalities were found in 0.02% group of both sexes. There were no significant differences in the incidences of any tumors among groups of both sexes. Based on these findings, the no observable effect level of formaldehyde was 0.02% in the drinking water (10 mg/kg body wt./day).

Administration, Oral