Biomedical subjects
Publications and source records attributed to Y Shimamoto.
An eighty-year-old man presented with recurrent annular erythema with pustules on the axillae, trunk, and groin consistent with a diagnosis of annular pustular psoriasis. Over the years, exacerbations of his skin lesions directly followed manic episodes. Use of major tranquilizers, including chlorpromazine, brought about a favorable remission of both the manic symptoms and the cutaneous lesions.
A case of a 62-year-old man with a large pericardial effusion is presented. He developed clinical signs of cardiac tamponade. Two-dimensional echocardiography revealed collapse of the right ventricle in early diastole and inversion of the free wall of both atria in systole. Pulsed Doppler echocardiography demonstrated an abnormally increased respiratory variation in transvalvular blood flow velocities. Expiration caused an increase in the flow velocities across the mitral and aortic valves, and a decrease in the flow velocity across the tricuspid valve. The exaggerated respiratory variations in transvalvular flow velocities suggest that Doppler evaluation may be a valuable adjunct in the diagnosis of cardiac tamponade.
A 57-year-old male was admitted to our hospital because of high fever and dyspnea. He had convulsive attacks after the operation for subarachnoid hemorrhage. He received an anticonvulsant, Hydantol F (Phenytoin + Phenobarbital), for 20 days before hospitalization. The white cell count on admission was 900/microliters without any neutrophils. Pseudomonas was demonstrated from blood cultures. After the anticonvulsant was discontinued and potent antibiotics were administered, his symptoms improved. Neutrophils appeared in the peripheral blood. We investigated the effect of phenytoin on the granuloid precursors using in vitro colony assay (CFU-C) after recovery from agranulocytosis. There was substantial decrease in CFU-C colony numbers when phenytoin or peripheral T-lymphocytes incubated with phenytoin was added in the culture. The addition of sera from acute phase did not affect the colony formation. These results suggested that direct toxic effect of the drug and cellular immunity played an important role in phenytoin induced agranulocytosis.
Forty-three patients with adult T-cell leukemia (ATL), admitted to the hospital from 1982 to 1987, were studied. Five of those were found to have additional cancer; two of the five had two additional kinds of cancers besides ATL. During the same period, in contrast, the authors encountered only three patients with some superimposed cancer among 155 cases of hematologic malignancies which had no association with human T-cell lymphotropic virus type I (HTLV-I). These facts strongly suggest that HTLV-I infection is not only associated with ATL, but it is likely to increase the incidence of other types of malignancy as well.
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Prognostic factors affecting the survival of adult T-cell leukemia (ATL) patients were analyzed in three groups: total cases, leukemia type cases, and lymphoma type cases. Factors found to be important overall, i.e. for total cases, were leukocyte count, ATL cell ratio in the peripheral blood, serum calcium levels and lactate dehydrogenase (LDH) level. Of those, LDH level proved not significant when evaluated separately for leukemia type or lymphoma type cases. Leukocyte count and ATL cell ratio were significant in leukemia type patients, whereas it was serum calcium level that was significant in lymphoma type; there were mutually exclusive sets of factors for the two groups. Thus, prognostic factors for ATL patients should be considered separately for each type of the disease.
Using a population-based cancer registry, we tabulated 69 definite adult T-cell leukemia/lymphoma cases (36 males and 33 females) and 2.20 expected cases (0.95 for males and 1.25 for females) diagnosed from 1981 to 1983 in Saga, Japan. The number of human T-lymphotropic virus type I carriers was computed by applying sex- and age-specific anti-human T-lymphotropic virus type I antibody positive rates among blood donors at the blood center in 1986 to the whole population of Saga Prefecture in 1982. The age-specific incidence rates among male human T-lymphotropic virus type I carriers from 40 to 79 yr of age per 100,000 were significantly higher than those of female carriers (P less than 0.05), and the rates from 60 to 69 yr of age were the highest in both sexes. The annual crude incidence rates among carriers were 115.9 for males and 66.4 for females. The summary incidence rates with 95% confidence intervals were 115.9 (58.4 to 193.0) for males and 65.9 (30.0 to 115.9) for females. The cumulative risks were 4.5% (0.8 to 11.0) for males and 2.6% (0.3 to 7.0) for females. These morbidity figures were assumed to be underestimated partly due to the newly proposed clinical entity of adult T-cell leukemia/lymphoma.
Forty-three cases of adult T-cell leukemia (ATL) admitted to our hospital between 1982 and 1987 were studied. Three of those were found to be complicated with diffuse panbronchiolitis (DPB). The incidence of DPB is considered to be significantly higher in patients with ATL. The three DPB-complicated cases composed one case each of the smoldering, chronic, and acute type of ATL. In each type, DPB preceded overt ATL and Candida albicans was found in sputa following detection for bacteria. The DPB complication apparently worsened the prognosis of the ATL patients. We have discussed a possible relationship between ATL and DPB.
Methods for pharmacokinetic modulation of the plasma 5-fluorouracil (5-FU) level to increase antitumor activity during continuous venous infusion (CVI) of low doses of 5-FU were examined in Yoshida sarcoma-bearing rats. These methods were additional infusion of 5-FU for a short period (4 h) or oral administration of UFT or Tegafur during long-term CVI of 5-FU that alone gave a plasma 5-FU level of about 50 ng/ml. The antitumor effect on Yoshida sarcoma was markedly potentiated when an additive dose of 5-FU combined with 3-cyano-2,6-dihydroxypyridine (CNDP), a potent inhibitor of 5-FU degradation, giving a plasma level of about 500 ng/ml, was infused for 4 h. A similar increase in the antitumor effect was observed with oral administration of a conventional dose of UFT during CVI of 5-FU without CNDP, giving a plasma level of 30 to 60 ng/ml. These results suggest that the antitumor effect of CVI of 5-FU can be potentiated by pharmacokinetic modulation of the 5-FU concentration in the blood.
The correlations of the 5-fluorouracil (5-FU) level in the plasma and the duration of continuous 5-FU infusion with the antitumor activity of 5-FU on Yoshida sarcomas in rats were examined. The circadian variation in the plasma level of 5-FU during continuous infusion was prevented by treatment with 3-cyano-2,6-dihydroxypyridine (CNDP), which strongly inhibits 5-FU degradation. On continuous venous infusion of 2 to 30 mg/kg of 5-FU over 24 h with CNDP at a molar ratio of 1:10 into normal rats, the 5-FU level in the blood was linearly proportional to the dose of 5-FU. The optimum schedule for antitumor activity on Yoshida sarcomas in rats was found to be infusion of 5-FU at 5 mg/kg over 24 h for 6 consecutive days, which gave a plasma 5-FU level of 176 ng/ml. Continuous infusion of 5-FU to give a plasma level of 300 ng/ml for 6 consecutive days from day 5 after implantation of tumor cells, when the tumors weighed about 1.0 g, resulted in complete regression of the tumors in all rats.
A compound containing both CNDP (3-cyano-2,6-dihydroxypyridine), an inhibitor of 5-fluorouracil (5-FU) degradation, and EM-FU (1-ethoxymethyl-5-fluorouracil), a masked form of 5-FU, was synthesized and named BOF-A2 (3-[3-(6-benzoyloxy-3-cyano-2-pyridyloxycarbonyl)benzoyl]-1-ethoxy methyl-5- fluorouracil). The antitumor activity of BOF-A2 was investigated in sarcoma-180-bearing mice and Yoshida sarcoma-bearing rats. The ED50 (the dose for 50% inhibition) values of BOF-A2 were 25 mg/kg against sarcoma-180 and 15 mg/kg against Yoshida sarcoma. In vitro studies showed that BOF-A2 was rapidly degraded to EM-FU and CNDP in homogenates of the liver and small intestine of mice and rats, and in sera of mice, rats and human, and the conversion of EM-FU to 5-FU occurred only in the microsomal fraction of rat liver in the presence of NADPH. After oral administration of BOF-A2 at 15 mg/kg to Yoshida sarcoma-bearing rats, BOF-A2 was hydrolyzed to EM-FU, CNDP and 5-FU, and their maximum concentrations in the blood were 2000 ng/ml, 300 ng/ml and 40 ng/ml, respectively. Moreover when BOF-A2 was given at the same dose to tumor-bearing mice and rats, the 5-FU levels in the tumor tissue increased much more than those in the blood and persisted for more than 8 h, whereas those in the blood decreased more rapidly. This accumulation and maintenance of a high level of 5-FU in the tumor tissue are concluded to be related to the high antitumor activity of BOF-A2.
A patient with acute lymphoblastic leukemia, who developed acute renal failure, was imaged by computed tomography (CT). Persistent wedge-shaped areas of low attenuation in the kidneys were shown by sequential scans but not areas of infarction were found at autopsy. This case suggests that a wedge-shaped low-density lesion on CT may occur not only in infarcted areas, but also in areas where patchy vasoconstriction occurs.
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Blood flow in the superior mesenteric artery was observed with a chronically implanted electromagnetic flow probe in two-kidney, one-clip renovascular hypertensive rats (2K1C), one-kidney, one-clip renovascular hypertensive rats (1K1C), and normotensive control rats (NCR) in the conscious state. Arterial pressure was recorded with an indwelling catheter. Superior mesenteric resistance was calculated as arterial pressure divided by superior mesenteric flow. In all three groups of rats, superior mesenteric resistance remained almost unchanged when arterial pressure decreased markedly on ganglionic blockade with hexamethonium bromide. However, subsequent injection of a vasopressin antagonist (Manning compound) decreased superior mesenteric resistance significantly in 2K1C but not in 1K1C and NCR. Injection of vasopressin antagonist alone was without effect on arterial pressure and superior mesenteric flow in the three rat groups. Only 2K1C were judged to have appreciable sympathetic tone in resistance vessels of the superior mesenteric area, which was blocked by hexamethonium but compensated for by secondarily secreted vasopressin.
The circadian rhythm of the heart rate was assessed using 24 hour electrocardiographic recordings in 18 hospitalized elderly patients with wasting diseases receiving total parenteral nutrition. The nutrient solutions were administered at doses ranging from 360 to 1640 kcal/day. To determine if the heart rate fluctuates rhythmically with a circadian period, the mean hourly heart rate on 24 hour electrocardiographic recordings was used to fit cosine curves by the statistical technique of least squares, and three parameters of the rhythm--designated the mesor, amplitude, and acrophase--were estimated. The cosine curves fitted with a P value of 0.01 or less in all patients before and after insertion of central venous catheters. The mesor represented the rhythm--adjusted mean of the heart rate. The mesor increased significantly with increase in the energy infusion rate (p less than 0.01). The amplitude values were derived from one half of the total diurnal variation of heart rate and the acrophase indicated the time when heart rates were at their peak above the mean. Neither amplitude nor acrophase changed significantly with increase in the energy infusion rate. Furthermore, neither norepinephrine nor epinephrine plasma levels changed with nutrient administration. There were no significant changes in thyroid hormone concentrations. There was a significant positive correlation between mesor changes and rectal temperature with increase in the energy infusion rate (r = 0.76, p less than 0.01). In severely malnourished subjects, changes in the level of feeding can profoundly affect cardiac functions and thermogenic response.
Thyroid function was investigated in 222 elderly euthyroid subjects (79.6 +/- 7.6 years, males 68, females 154). Serum free T3, free T4, and TSH levels were measured by radioimmunoassay. To assess the factors influencing serum free T3 and free T4, we applied multiple regression analysis. 1) Serum free T3 concentrations were directly proportional to both serum albumin levels and hemoglobin levels. Serum free T3 levels were lower in bedridden male subjects and in female subjects with dementia. 2) Serum free T4 concentrations were negatively correlated to serum TSH levels in male. Serum free T4 levels were higher in bedridden female subjects, and increased in proportion to serum albumin concentrations in females. 3) Age had no apparent effect on either serum free T3 or free T4 concentrations.
The influence of thyroid function on the circadian rhythm of heart rate was assessed using 24 hour electrocardiographic recordings in 196 elderly euthyroid subjects (78.4 +/- 8.1 years; male 60, 76.1 +/- 9.1 years; female 136, 79.4 +/- 7.4 years). Serum free T3, free T4 and TSH levels were measured by radioimmunoassay. To determine if heart rate fluctuates rhythmically with a circadian period, mean hourly heart rates in 24 hour electrocardiographic recordings were used to fit cosine curves by the statistical technique of least squares, and the parameters of the rhythm--the mesor, amplitude, acrophase, maximal and minimal hourly heart rates--were estimated. To investigate the factors influencing the diurnal variation of heart rate, we applied multiple regression analysis. The cosine curves were fitted with a P value of 0.01 or less in all subjects. The mesor, maximal and minimal hourly heart rates were inversely proportional to serum TSH concentrations in males. Neither amplitude nor acrophase had relation to the thyroid function in males. The mesor, maximal and minimal hourly heart rates were directly proportional to serum-free T4 concentrations and inversely proportional to serum TSH concentrations in females. The increase in the acrophase correlated with the increase in serum-free T4 levels, and the acrophase increased in proportion to serum-free T3 levels in females.
A 59-year-old man was admitted to the Saga Medical School Hospital in November 1986 because of unconsciousness and lymph node swelling. He had café au leit spots and multiple neurofibromas since his thirties. The leukocyte count was increased. The level of serum LDH and Ca were extremely elevated. His bone marrow aspiration showed the invasion of lymphoma cells. Lymph node biopsy from his left neck and the study of surface markers were performed. And then, his illness was diagnosed as non-Hodgkin's lymphoma (diffuse, medium sized cell type, B cell type, stage IV B.) following von Recklinghausen's disease. After the admission, his general condition improved by chemotherapy, but he had a relapse 6 months later. And he died in November 1987. The case of von Recklinghausen's disease associated with malignant lymphoma in rarely reported. We reviewed the literature and discussed von Recklinghausen's disease associated with malignant lymphoma including this case.