Biomedical subjects
Publications and source records attributed to H Manabe.
Hypoglycemia is known to be a rare consequence of non-islet cell tumors. A patient having severe, episodic hypoglycemia was found to have a large mass occupying the right hemithorax. The hypoglycemia resolved immediately after surgical removal of the tumor. Histologic examination of the tumor revealed localized fibrous mesothelioma.
Multiple pulmonary nodules were found in a patient who had an occupational history of coal mining for eleven years and road construction for fifteen years. An open lung biopsy was performed, because nodules had increased in size compared to previous ones and a trasbronchial biopsy was not diagnostic. The nodules were composed of dense concentric lamellar collagenous structures with a serpentine pattern surrounded by an infiltration of histiocytes, lymphocytes and plasma cells with Russel bodies. These findings are compatible with pulmonary hyalinizing granuloma (PHG) named by Liebow A. A. The etiopathogenetic mechanism and the difference between PHG and silicotic nodule is discussed.
OBJECTIVE: The purpose of this study was to investigate the effects of continuous epidural blockade on acute zoster-associated pain, compared with intermittent epidural blocks. DESIGN: The design was a retrospective, nonrandomized study. SETTING: The study was conducted at a university hospital in Japan from 1982 through 1992. PATIENTS: A total of 178 otherwise healthy patients hospitalized with moderate or severe herpes zoster lesions. INTERVENTIONS: Group A (n = 66) had intermittent epidural blocks using 1% mepivacaine, 4-6 ml, three to six time daily; group B (n = 43) were given intermittent epidural blocks and parenteral acyclovir (500 mg/day) or vidarabine (600 mg/day) for 5 days; group C (n = 69) were administered a continuous epidural 0.5% bupivacaine infusion (0.3-1.0 ml/h) for approximately 2 weeks and antiviral agents followed by intermittent blocks. MAIN OUTCOME MEASURES: The number of treatment days was used as the outcome measure. RESULTS: The length of treatment was significantly shorter in group C than in groups A or B. For moderate lesions the means (days) were 36.2 [95% confidence interval (CI), 31.4-41.7), 45.6 (95% CI, 34.0-61.4), and 26.8 (95% CI, 22.3-32.3) for groups A, B, and C, respectively (p < 0.01). For severe lesions they were 73.3 (95% CI, 55.1-97.7), 81.7 (95% CI, 59.1-113.0), and 44.9 (95% CI, 35.2-57.3) for groups A, B, and C, respectively (p < 0.01). CONCLUSIONS: Continuous epidural blockade for patients with acute zoster can shorten the duration of treatment and may reduce the incidence of postherpetic neuralgia.
An intra-pulmonary mass in a 51 year old Japanese woman was incidentally discovered in the right middle lobe. The resected tumor was grossly well-demarcated, solid, light yellowish white in color and measured 3.0 x 2.0 x 1.5 cm in size. It was composed of a diffuse proliferation of large polygonal cells with an abundant, granular cytoplasm, and round to irregular nuclei with prominent nucleoli. Smaller eosinophilic cells with hyperchromatic nuclei and larger vacuolated cells were also observed. However, no mucin production was detected. There were neither argyrophilic nor argentaffin cells, and no serotonin-positive cells. They showed an immunoreactivity to cytokeratin and vimentin but not to alpha-actin. On electron microscopy, abundant microvilli, which have never been previously described in pulmonary oncocytomas, were observed. Occasional desmosomes and myelin figures as well as numerous mitochondria were also seen. No neurosecretory granules were present. These findings suggested that this tumor might have an epithelial origin from the bronchial serous gland with subsequent cellular degeneration.
Effect of KW-4679, an antiallergic agent, on the experimental allergic rhinitis was studied in guinea pigs. 1) KW-4679 inhibited the sneeze response and the nasal rubbing induced after the intranasal administration of antigen in sensitized guinea pigs. The inhibitions were dose-related and significant at 0.03 mg/kg p.o. for sneeze response and 1 mg/kg p.o. for nasal rubbing, respectively. 2) The nasal vascular permeability was increased after the intranasal administration of antigen in sensitized guinea pigs. KW-4679 significantly reduced the increase of the nasal vascular permeability at 1 mg/kg p.o. or higher. From these results, KW-4679 may have inhibitory effects on sneeze, nasal irritation and rhinorrhea in clinical use.
The new ceiling mount with the "Space Pointer/Cygnus" system for the Leica Wild M690 operating microscope (Leica AG, Heerbrugg, Switzerland) is reported. Two modes of action, "focus lock" and "point lock", are used with this system, in addition to counterbalanced free motion and electromagnetic brakes. The system also considerably improves space factors around the microscope.
BACKGROUND AND PURPOSE: Serial changes of anti-platelet-aggregating activity in the endothelial cells after experimental subarachnoid hemorrhage were studied in 30 feline two-hemorrhage models. METHODS: One hour or 2, 4, 7, or 14 days after mimic subarachnoid hemorrhage, ADP (40 mg/kg) was infused into the basilar artery via the right vertebral artery to activate circulating platelets. Immediately after ADP infusion, the basilar artery was fixed by intra-arterial perfusion with 1.5% glutaraldehyde in 0.1 mol/L phosphate buffer and was removed. The luminal surface was examined under a scanning electron microscope. RESULTS: One hour after subarachnoid hemorrhage, no platelets adhered or aggregated on the luminal surface. However, 4 to 7 days after subarachnoid hemorrhage, many platelets were observed adhering or aggregating on the luminal surface. CONCLUSIONS: These findings suggest the impairment of anti-platelet-aggregating activity of endothelial cells after subarachnoid hemorrhage. This impairment may be involved in inducing cerebral ischemia during cerebral vasospasm by causing platelet adhesion and aggregation.
In order to develop new oral bronchodilators, a series of novel imidazol[4,5-c][1,8]naphthyridin-4(5H)-ones 5 were designed and synthesized. Some of these new heterocycles exhibited more potent bronchodilator activity in vitro and in vivo than theophylline. With respect to modification at the 5-position, both phenyl and n-butyl substitution produced potent activity. Though bulk tolerance at N-3 is observed with short and small lipophilic groups, any substitution at the other positions and transformations of the parent skeleton eliminated activity. Thus 5-phenyl-1H-imidazo[4,5-c][1,8]naphthyridin-4(5H)-one (23) (KF17625), which satisfied these conditions, was selected for further studies (antigen inhalation-induced bronchospasm model; minimum effective dose (MED) = 1 mg/kg, po; antigen-induced contraction of trachea (the Schultz-Dale reaction), IC50 = 2.2 microM). Compound 23 inhibited carbachol-, histamine-, or leukotriene D4-induced contraction and relaxed spontaneous tone in guinea pig isolated tracheal preparations with, 4- to 16-fold greater potency than aminophylline. Thus it appeared to relax directly the airway smooth muscle. 23 did not have any influence on adenosine binding at 10 microM, but inhibited canine tracheal phosphodiesterase (PDE) IV (IC50 = 12 microM) and concanavalin-A-induced histamine release from rat mast cells (44% inhibition at 10 microM). Although the detailed mechanisms of these compounds remain to be elucidated, this series of novel tricyclic heterocycles represents a new class of bronchodilator.
A series of novel xanthine-based tricyclic heterocycles in 1H-imidazo[4,5-c]quinolin-4(5H)-ones was designed, synthesized, and tested as potential active bronchodilators. Inhibition of the Schulz-Dale (SD) reaction-induced contraction in trachea and inhibition of antigen inhalation-induced bronchospasm in passively sensitized guinea pigs served as primary in vitro and in vivo assays, respectively. Simultaneous measurement of acute lethal toxicity (minimum lethal dose; MLD, po) in mice allowed determination of a safety margin. The bronchodilatory activity of these heterocycles was considerably varied with the nature of substituents at the 5-position. The most active substituents at the 2- and 5-positions and on the aromatic ring were found to be hydrogen, n-butyl, and hydrogen, respectively. There was a bulk tolerance for lipophilic substituents at the 1-position. 5-Butyl-substituted compounds appeared to be less toxic than theophylline on the basis of MLD data. Thus 5-butyl-1-methyl-1H-imidazo[4,5-c]quinolin-4(5H)-one (10) (IC50 value of the SD assay = 0.25 microM, MLD > 300 mg/kg) was selected for further studies. Compound 10 (KF15570) reduced bronchoconstriction produced by antigen (Konzett-Rössler preparation in anesthetized guinea pigs, ED50 = 0.42 mg/kg, iv) more effectively than aminophylline (ethylenediamine salt of theophylline, ED50 = 7.8 mg/kg, iv) but had fewer side effects on the heart and CNS than theophylline. Compound 10 and its derivatives showed weak adenosine antagonism and phosphodiesterase (PDE) inhibition which could not account for their potent bronchodilation. Although their precise mechanism of action remains unclear, this series of novel tricyclic heterocycles represents a new class of bronchodilator.
A hospital-based case-control study was conducted to evaluate occupational risks of lung cancer in an industrialized city of Japan. The lung cancer cases were obtained from 3 major hospitals in the city. The control group consisted of patients with a variety of diseases hospitalized in the same wards of the same hospitals as the cases. After matching on sex, 5-year age category and hospital, 144 cases and 676 controls comprised the study group. A self-administered questionnaire was used to obtain lifetime job histories and smoking status. The conditional logistic regression model was used to estimate relative risks after controlling for smoking and employment in other jobs. The workers in shipbuilding, ironworks and other plants (mostly chemical plants) showed statistically significant increases in lung cancer risk with relative risks of 6.18, 2.02, and 2.66, respectively. An increase in risk with the duration of employment was also observed in the "other plants" category. Building and road construction workers also showed increased relative risks, 1.95 and 1.79, but they were not significant. When the risk was evaluated on the exposure chemicals, the workers exposed to inorganic acids and bases had significantly increased risk. The workers exposed to asbestos, dust or organic chemicals also showed increased risk but the effects were not significant. The combined effect of smoking and employment in ironworks showed a good fit to an additive model, while that in the "other plants" category was closer to a multiplicative model.
A series of novel 3-substituted imidazo[4,5-c]quinolin-4(5H)-ones (2a-w) was prepared by the reaction of imidazo[4,5-c]quinolin-4(5H)-ones (6) with several electrophiles under basic conditions. The bronchodilatory activity of these compounds was evaluated on the basis of their protective effects against antigen-induced contraction (the Schultz-Dale reaction) of guinea-pig trachea (in vitro) and antigen inhalation-induced bronchospasm in passively sensitized guinea-pigs (in vivo). Although correlations between in vitro and in vivo activities were not clear, short alkyl chains such as the methyl and ethyl groups at the 3-position were important for potent activity, especially in vivo. Substituents at the 5-position were more tolerant of the activity than those at the 3-position. 5-Ethyl-3-methyl-3H-imidazo[4,5-c]quinolin-4(5H)-one (21) exhibits the most potent bronchodilatory activity among our tested compounds and is at least 5-fold more active than theophylline in vivo.
Sixteen patients with acute profound heart failure (HF) have been treated with the left ventricular assist device (LVAD), nine of them were successfully weaned from LVAD, and three of them were discharged and survived longer. Decompression of the left ventricle (LV) at the beginning will prevent overextension of impaired myocardium and accelerate scar formation. Gradual increase of LV work will promote the compensation ability of the residual myocardium. We found that continuous LVAD assistance can give time for the impaired heart to recover while maintaining normal circulation. For patients with profound HF which is beyond the limit of intra-aortic balloon pumping's (IABP) capability, LVAD is a more powerful and effective means. Although the heart recovered, many patients later died of multiple organ failure (MOF) which was probably caused by prolonged ischemia before LVAD application. For completely successful recovery from profound HF, diagnosis and deciding to use LVAD should not be delayed. It should be applied before major organs including the heart itself suffer irreversible damage. We have established a systematic therapeutic concept of treating acute HF patients using assisted circulation including LVAD.
A teratological study of suplatast tosilate (IPD-1151T), a newly developed anti-allergic agent, was carried out in pregnant NZW rabbits to assess the effects on dams and fetuses. IPD-1151T was administered to dams orally at dose levels of 0, 100, 300, 450 and 700 mg/kg/day from day 6 through day 18 of gestation, and their fetuses were removed for teratological evaluation. The results were as follows: 1. In dams, marked increase in the incidence of abortion, and decrease in body weight gain, food consumption and feces mass were shown in the 700 mg/kg/day group. Slight decrease in body weight gain and food consumption were seen in the 450 mg/kg/day group, but no toxicities were observed in the 300 mg/kg/day or less groups. 2. In fetuses, marked increase in embryo-fetal deaths and decrease in alive fetal body weights and placental weights, but no teratogenicity were shown in the 700 mg/kg/day group. There were no fetal toxicity or teratogenicity in the 450 mg/kg/day or less groups. 3. No effective dose levels were 300 mg/kg/day for maternal general toxicity and 450 mg/kg/day for maternal reproductive toxicity and for fetuses.
Antigenicity of suplatast tosilate (IPD-1151T) was investigated in guinea pigs and mice. The results were as follows: 1. Homologous passive cutaneous anaphylaxis (PCA), active systemic anaphylaxis (ASA), active cutaneous anaphylaxis (ACA) and Schultz-Dale reaction tests were carried out using guinea pigs which were immunized orally with IPD-1151T alone or subcutaneously with IPD-1151T and Freund's complete adjuvants (CFA). Positive reactions in these tests were not produced by eliciting injection of IPD-1151T or its metabolite, M-1. On the other hand, the sensitization of ovalbumin (OVA) with CFA produced positive reactions in all of PCA, ASA, ACA and Schultz-Dale tests. 2. Heterologous passive cutaneous anaphylaxis (PCA) test using rats was carried out using two strains of mice (C3H/He and BALB/c) which were immunized orally with IPD-1151T alone or intraperitoneally with IPD-1151T and aluminum hydroxide gel (Alum) as an adjuvant. No animals showed positive reaction to both eliciting antigens, IPD-1151T and M-1. On the other hand, a positive reaction in PCA test to eliciting antigen, OVA, was obtained in rats treated with sera of mice sensitized with OVA plus Alum. 3. These findings showed that IPD-1151T had no antigenicity in guinea pigs and mice.
The dura mater adjacent to the attachment of meningiomas was enhanced on MR imaging with intravenous Gd-DTPA infusion. It was examined histologically in four patients with intracranial globoid meningiomas. Histological examination revealed that there was no tumor cell invasion within the dura mater enhanced on MR imaging, except at the point of their attachment. A layer of tumor cells was occasionally observed on the surface of the dura mater, but this was limited to within 5 mm of the tumor margin. Our electronmicroscopic observation indicated that enhancement of the dura mater adjacent to the attachment of meningiomas was caused by increased vascular permeability of the dural vessels and extended extravascular space.
The purpose of this study is to examine the feasibility of long-term circulatory maintenance with only a left-sided single artificial heart that is inserted between the left atrium and the aorta to assist a nonfunctioning heart. The basic hemodynamics were determined in short-term experiments in goats (n = 4), and feasibility studies of long-term circulatory maintenance with a single artificial heart during cardiac arrest were performed in long-term experiments (n = 12). When pulmonary vascular resistance was less than 15,000 dynes .sec.cm-5.kg, which was twice the normal value, the circulation was well maintained with the single artificial heart alone, so long as the right atrial pressure was kept at 14 to 16 mm Hg. Under such conditions the flow yielded by the single artificial heart fluctuated between 80 and 140 ml/kg/min depending on the animal's demand, while the mean arterial pressure was kept above 80 mm Hg. The goats behaved normally, although retention of pleural effusion was a serious problem in maintaining normal circulation over a long-term. Maintaining the plasma total protein level above 6.0 gm/dl delayed the onset of retention or even prevented pooling of pleural effusion. The longest survival period to date has been 38 days. We conclude that when the pulmonary vascular resistance is less than twice the normal value and the total protein level is above 6.0 gm/dl, a left-sided single artificial heart alone can maintain normal circulation and provide time for patients with a nonfunctioning heart to undergo a further treatment, such as heart transplantation.
Giant cell carcinomas of the lung have been notorious in fulminant clinical courses. Thus, this report describes two exceptionally favorable cases among six cases of giant cell carcinoma of the lung. Their histopathological features are a sharply-demarcated tumor of Stage I, absence of vascular permeation of the cancer cells, prominent lymphoid and plasma cell infiltration in the tumor tissue, and lymph follicle formation in the surrounding tissues. Another case with a Stage II tumor showed the same histopathological findings as the above two cases with the exception of lymphatic permeation of the cancer cells. This patient expired about one year after undergoing an operation. As conventional controls, the remaining three cases with Stage III tumors showed an alveolar extension of tumor cells and vascular permeation. There was a fulminant course after the operation. Notwithstanding similar intervals from their clinical onset to operation in the 4 cases other than Cases 4 and 6, their stages showed considerable variations. Hence, each histopathological feature might have substantiated the different clinical courses following the operation. Electron microscopy of three of the cases indicated double-membrane-bound blisters with intermediate junctions in the bizarre giant cells, and cancer cell differentiation toward both glandular and squamous directions.
We report the rare case of ipsilateral posterior inferior cerebellar artery originating from the carotid artery, and associated with multiple concurrent aneurysms. This is the 23rd reported case of carotid-cerebellar anastomosis and the first case with three concurrent aneurysms reported in the literature. Of the 23 cases, 6 had single aneurysms, 2 had double aneurysms and the present case had triple aneurysms.