[Prediction of 3-year outcome and clinical typology in inpatient alcoholics].
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Adult↗
Biomedical subjects
M Kato
Publications and source records attributed to M Kato.
Bone morphogenetic protein receptors and activin receptors are highly expressed in ossified ligament tissues of patients with ossification of the posterior longitudinal ligament.
Ossification of the posterior longitudinal ligament (OPLL) is a pathological ossification in the spinal ligament, with formation of ectopic bone mainly through endochondral ossification. Bone morphogenetic proteins (BMPs) and activins are multifunctional proteins that belong to the transforming growth factor-beta superfamily and that have been implicated in the formation of new bone and cartilage. BMPs and activins signal via type I and type II receptors for BMPs (BMPRs) and activins (ActRs), respectively. OP-1/BMP-7 binds to BMPR-II and ActR-II and forms complexes with BMPR-IA and -IB and ActR-I. We studied the expression of BMPR-IA, -IB, and -II, ActR-I, ActR-II, and OP-1/BMP-7 by immunohistochemistry in ossified ligament tissues of patients with OPLL and control ligament tissues from patients with cervical disc herniation. The expression of BMPRs and ActRs was elevated in OPLL compared with controls. Expressions of BMPR-IA, -IB, and -II were observed not only in chondrocytes at the fibrocartilage tissue around the calcified zone but also in fibroblast-like spindle cells at the nonossified ligament. ActR-I and -II were found co-localized in the hypertrophic chondrocytes near the calcified zone and in the ossified tissue. OP-1/BMP-7 was expressed in chondrocytes near the calcified zone. In the control cases, the BMPRs and ActRs were only weakly expressed in the fibrocartilage tissue at the site of ligament attachments to bone and OP-1/BMP-7 was not detected. Enhanced expression of BMPRs at the nonossified ligament in OPLL patients suggests that these cells have a greater potential to differentiate into osteogenic cells than ligament cells from non-OPLL patients. The high expression of BMPRs and ActRs in the ectopic ossified ligament suggests that BMPs and activin may be tightly involved in the pathological ossification process of OPLL.
Activin Receptors↗
[Trial of radiation and cisplatin, carboplatin combination chemotherapy for advanced cancer (W-platinum chemoradiotherapy].
Cisplatin was reported to be an effective radiation sensitizing agent. The effect was also reported to depend on dose intensity. But the incidence of complication was demonstrated in the relationship with the dose escalation curve of anti-cancer agent. The major side effect of CDDP was occasionally serious, as in renal toxicity or bone marrow suppression. W-Platinum is the trial of concurrent chemoradiotherapy. Cisplatin and its derivative, Carboplatin, were selected as effective radiation sensitizing agents and to obtain high-dose intensity and additive cytotoxicities by interaction between the two drugs. Concomitant administration of two platinum anti-cancer agents has the advantage of reduction of side effects compared with administration of single anti-cancer agents to the same degree. The first case was a recurrence of epipharyngeal cancer after 3 courses of chemotherapy, including CDDP or CBDCA. This case was suspected to be cancer-resistant to CDDP. The second case was post-operative residual lung cancer. The pre-operative diagnosis was stage III A. A poor prognosis was expected. This case was disease-free and alive for 1 year after W-Platinum administration. The most frequent complication was bone marrow suppression. Patients were rescued from bone marrow suppression with administration of G-CSF. Renal toxicity could be suppressed with sufficient hydration.
Adenocarcinoma↗
[Roles of the basal ganglia outputs in movement disorders: a viewpoint based on experiences of stereotactic surgery for idiopathic dystonia].
Ventrolateral (VL)-thalamotomy and posteroventral pallidotomy were carried out in 37 patients with idiopathic dystonia, including 23 with dystonia musculorum deformans, 12 with Meige syndrome and 2 with focal dystonia. There were 11 patients with the onset age of dystonia below 10 years and 26 with the age above 11 years. Dystonia tended to generalize in the pediatric patients and to localize to the palmo-mental region in the adult patients. VL-thalamotomy in 30 patients improved the upper body dystonia especially in the adult patients, but, often failed to benefit the pediatric patients. Posteroventral pallidotomy in 18 patients dramatically alleviated the generalized dystonia especially in the pediatric patients. In one adult patient, pallidotomy caused hemiparesis due to intracerebral hemorrhage. The internal pallidum projects the efferents to the thalamic motor nuclei and also to the brainstem reticular formation that connects to the spinal motoneurons. The present findings implicate the descending pallido-reticular pathway in the mechanism of dystonia of pediatric patients, and the ascending pallido-thalamic pathway in that of adult patients.
Adolescent↗
Evaluation of combined therapy with chemoembolization and ethanol injection for advanced hepatocellular carcinoma.
To evaluate the therapeutic efficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous ethanol injection therapy (PEIT) for advanced hepatocellular carcinoma, we studied the effectiveness of TACE therapy combined with PEIT (50 cases) and TACE alone (50 cases). In both groups, patients had multiple lesions, or a single lesion with a diameter exceeding 2 cm or with vascular invasion (stages II, III, and IV in the tumor staging classification of the Liver Cancer Study Group of Japan). The clinical features in the two groups were comparable. The cumulative survival rates with TACE-PEIT were 95.0% for 1 year, 72.5% for 2 years, and 50.0% for 3 years, whereas the rates with TACE alone were 92.5% for 1 year, 57.5% for 2 years, and 20.0% for 3 years. The survival rate in the TACE-PEIT group was significantly higher than that in the TACE alone group. Moreover, the survival rate of patients with stage II or III disease in the TACE-PEIT group was significantly better than that in the TACE alone group, and the survival rate of patients with Child's classification B or C in the TACE-PEIT group was significantly higher than that in the TACE alone group. Multivariate analysis using Cox's proportional hazard regression model showed that the most significant prognostic factors in the TACE-PEIT group were tumor embolus in the portal vein and the number of tumors. These results suggest the effectiveness of combining TACE and PEIT for the treatment of advanced hepatocellular carcinoma.
Antibiotics, Antineoplastic↗
[Factors affecting exercise capacity after coronary bypass grafting].
In order to determine the contribution of cardiac reserve and the peripheral muscle to exercise capacity in patients after Coronary Artery Bypass Grafting (CABG), 19 patients (18 males, 1 female, mean age 63.3 +/- 7.1 years, mean numbers of grafting 2.5 +/- 0.8) performed exercise tests at 1 week, 3 weeks, and 3 months after CABG. Ventilatory gas was analyzed throughout the testing and anaerobic threshold (AT) and peak oxygen uptake (peak VO2) was determined. During exercise testing, the cardiac index (CI) was measured, and the change in CI during exercise, delta CI = (CI at peak exercise) (CI at rest), was calculated. O2 delivery was derived from the product of CO and the oxygen content of arterial blood at peak exercise. The sectional area of the thigh muscles at the level of 10 cm above the patella was measured using a computed tomography before each test. Average peak VO2 at 1 week after CABG was 867 +/- 171 ml/min and it increased to 1,214 +/- 246 ml/min at 6 months. Average AT did not change from 1 week to 3 weeks, however, it increased significantly from 665 +/- 122 ml/min at 3 weeks to 873 +/- 181 ml/min at 6 months. The muscle area of the thigh increased significantly from 170 +/- 24 cm2 at 3 weeks after CABG to 186 +/- 27 cm2 at 3 months. delta CI showed a tendency to increase from 6.6 +/- 1.2 l/min/m2 at 1 week after CABG to 7.3 +/- 1.3 l/min/m2 at 3 weeks, and also showed a tendency to increase from 3 weeks to 6 months. Peak VO2 and AT correlated to delta CI at 1 weeks and also it correlated significantly to both the muscle area of the thigh and delta CI at 3 weeks, 3 months, and 6 months after CABG. The delta value of peak VO2 from 1 week to 3 weeks showed a significant correlation to those of delta CI and O2 delivery. Moreover, the delta values of peak VO2 and AT from 3 weeks to 3 months showed a correlation to those of delta CI and O2 delivery. These results suggest that both cardiac reserve and peripheral factors contribute to the exercise capacity up to 3 months after CABG, and, in particular, O2 delivery are important to increase exercise capacity.
Cardiac Output↗
Structure-activity relationships of spontaneous nitric oxide releasers, FK409 and its derivatives.
(+/-)-(E)-4-Ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409) shows both potent in vitro vasorelaxant and antiplatelet activities via nitric oxide (NO) generated spontaneously from the compound. In this study, we measured spontaneous NO-releasing rates of a series of FK409 derivatives, of which chain lengths or substituents were systematically modified, in sodium-phosphate buffer solution at pH 7.4. Furthermore, we studied their in vitro antiplatelet and vasorelaxant effects to evaluate relationships between spontaneous NO-releasing activities of FK409 analogs and their biological activities. FK409 derivatives were found to possess different spontaneous NO-releasing rates and biological activities according to their structural modification. In addition, these studies revealed a close correlation between NO-releasing rates of FK409 derivatives and their in vitro antiplatelet activities in human platelet-rich plasma, whereas the in vitro vasorelaxant activities of these compounds in isolated rat aorta did not correlate with the rates of NO liberation. The vasorelaxant effects were supposed to be affected by the structural properties of FK409 derivatives as well as their NO-releasing abilities.
Animals↗
[A semantic-pragmatic learning disabled child who showed a discrepancy between the abilities of verbal and non-verbal comprehension].
A learning disabled (LD) child with disorder of verbal semantic comprehension was reported. This case showed normal ability of non-verbal semantic comprehension. He was not able to understand the meaning of what he read aloud and/or repeated, which he did well. The focus of his brain dysfunction in the left temporal lobe was revealed by SPECT in spite of MRI findings of no particular lesions. Neuropsychological and cognitive-psychological findings were similar to those reported of adult sensory aphasias with localized lesions.
Child↗
[Non-Hodgkin's lymphoma associated with cold agglutinin disease].
Autoimmune hemolytic anemia (AIHA) complicated with non-Hodgkin's lymphoma (NHL) is not unusual. Two cases of NHL associated with cold agglutinin disease were reported. Case 1: A 38-year-old man had diffuse medium-sized cell NHL diagnosed by cervical lymph node biopsy. The Hb was 7.6 g/dl with a cold agglutinin titer of 32,768, and the IgM level was 890 mg/dl (I-specific), so cold agglutinin disease (CAD) was suspected. After administration of COP-BLAM therapy, complete remission (CR) was achieved along with a decrease in the cold agglutinin titer and improvement of anemia. Case 2: A 68-year-old woman had follicular mixed NHL diagnosed by inguinal lymph node biopsy. The Hb was 8.2 g/dl with a cold agglutinin titer of 51,200, and an IgM level of 920 mg/dl (I specific), thus concurrent CAD was suspected. Biweekly COP-BLAM therapy was administered and CR was achieved along with a decrease in the cold agglutinin titer and improvement of her anemia. In both patients, the cold agglutinin titer decreased after CR was achieved suggesting that production of anti-erythrocyte autoantibody was due to disturbance of the antibody system by NHL.
Adult↗
Pathological characterization of astrocytic hyaline inclusions in familial amyotrophic lateral sclerosis.
To clarify the pathological characteristics of astrocytic hyaline inclusions (Ast-HIs) in patients with familial amyotrophic lateral sclerosis (FALS) with neuronal Lewy-body-like hyaline inclusions (LBHIs), eight autopsies on members of four different families, including two long-term surviving patients with clinical courses of over 10 years, were analyzed. Ast-HIs were found only in the two long-term surviving patients who belonged to different families and to different races. Ast-HIs were ultrastructurally composed of 15- to 25-nm granule-coated fibrils that had immunoreactivities to superoxide dismutase 1 (SOD1) and ubiquitin. Approximately 50% of the Ast-HIs expressed alpha B-crystallin, metallothionein, glutamine synthetase, and tubulin (alpha and beta) at various intensities. Some Ast-HIs reacted with antibodies to tau protein, S-100 protein, and heat shock protein 27. The Ast-HIs were not stained for glial fibrillary acidic protein. Our results suggest a cooperative role of superoxide dismutase 1, ubiquitin, and cytoskeletal proteins in the formation of granule-coated fibrils (namely, Ast-HIs) and provide evidence that Ast-HIs are formed in certain long-surviving familial amyotrophic lateral sclerosis patients with neuronal Lewy-body-like hyaline inclusions.
Adult↗
[Dialysis-induced hypotension].
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Humans↗
[Study of diazepam with quantitative EEGs taken with eyes opened and topography].
Diazepam is a representative drug of benzodiazepines. The subjects were 9 right-handed healthy male volunteers 21 25 years of age. Double blind crossover trials with placebo control were conducted in a random sequence at an interval of 1 week. Diazepam 10 mg and placebo were administered as single oral doses. Three-minute EEGs were recorded with subjects' eyes opened before and 2 h after drug administration. One-minute out of the 3-minute EEGs was analyzed with FFT, and the absolute amplitude power (microV) was calculated. These results were subjected to Student's t-test (double difference) and displayed with topographic maps (t statistic significance probability mapping). Diazepam decreased the delta absolute amplitude power over left-parietal dominance, theta absolute amplitude power diffusely and alpha absolute amplitude power over parietal region dominance. It also increased the beta absolute amplitude power over left-antero-temporal region dominance. The EEG profiles taken with subjects' eyes open were different from those of diazepam with eyes-closed vigilance controlled concerning the degree of decrease of delta and beta activities and region of the effect on alpha activity.
Adult↗
[Autobiographical memory loss following herpes encephalitis].
We report a patient with prominent autobiographical memory (ABM) impairment, and discussed possible mechanisms of her deficits. The patient was a 36-year-old woman who suffered from herpes simplex encephalitis in November 1994. Four months after the onset, the neuropsychological examination disclosed that her intelligence, attention, language and frontal lobe functions were normal. Moderate anterograde amnesia was evident for visual materials, and she showed difficulties in retrieving visual images. Deficits in verbal learning were minimal. In contrast, her retrograde amnesia (RA) was severe. Further analyses clarified that memory for public events and personal semantic memory were relatively well preserved whereas ABM was severely impaired with no evidence of temporal gradient. Her performance on the ABM questionnaire was even worse than that of alcoholic Korsakoff patients. Interestingly, however, deficits in memory for public events also emerged when questions were presented with pictures instead of ordinary verbal questionnaires. The results suggest that her principle deficits consisted in utilizing visual information of the past events. Her access to and manipulation of the past visual representation/images were impaired. Consequently, her deficits were almost exclusive to ABM because visual information is most crucial for ABM. This material specific ABM impairment demonstrated in the present patient could be differentiated from nonspecific retrograde amnesia observed in typical focal RA patients. MRI, SPECT and PET demonstrated that the present patient had lesions basically in the right hemisphere, specifically in the medical temporal area including the hippocampus.
Adult↗
[An analysis of telephone health counseling for Japanese employees and their families abroad, "Japan health Care Line (overseas)"].
In the past 6 years, the "Japan Health Care Line" has accumulated over 2,000 cases of telephone counseling calls, mainly on health problems, by Japanese living abroad on business, and their families, in 55 countries. The characteristics of these Japanese from medical aspects (physical and psychological), life style, and education were determined; and factors that influence their life abroad as well as some of their problems were analyzed. The role that telephone counseling can play in alleviating their anxiety, in helping them adapt, and in maintaining their health was also examined. The clients were Japanese employees and their families whose health insurance associations had joined this service. Data were recorded on a card for 14 items-the caller, the person needing the advice, age, sex, area of residence, length of stay, hour of call, number of calls etc. The data and main complaints were categorized in three ways: 1) by medical fields for business reports; 2) by coding the complaints; and 3) by the ICD-10 classification. Of the callers, 80% were in their 20's and 30's, meanwhile, as to the persons who need the advice, 30% of them were under 10, and 30% were in their 30's. There were many cases in obstetrics-gynecology, pediatrics, and general medical information. In the contents of the counseling, conditions or symptoms of the client were foremost, and together with advice on treatment, comprised half the calls. A study was made on the correlation between the clients' length of stay/location and the main complaints. Clients living abroad less than 1 year tended to call more, especially for vaccination, translation, mental problems, and medical systems, but did not call much in fields of obstetrics-gynecology, dentistry-oral surgery, examination data and treatments. Location did not make much difference in the fields of consultations, except for obstetrics-gynecology and dermatology. Middle and Near East countries had special characteristics to their consultations. There were differences in fields of counseling in calls from developing countries and developed countries. In the former countries, calls on orthopedics, urology, tropical diseases, and infectious diseases were numerous, while in the latter, pediatrics and mental problems were.
Adolescent↗
Immunological response to repeated administration of recombinant human erythropoietin in rats: biphasic effect on its pharmacokinetics.
We studied changes in the pharmacokinetics of 125I-recombinant human erythropoietin (125I-rh-EPO) after repeated subcutaneous administration once a week for 4 weeks. The plasma level of trichloroacetic acid-precipitable radioactivity after the fourth administration of 125I-rh-EPO was minimal in 8 of 10 rats, whereas in the other two rats, the plasma level was almost the same or somewhat higher than that in control rats that had received the vehicle solution 3 times instead of the first three sequential administrations. Antibody against rh-EPO in serum was detected in all 10 rats receiving multiple administrations of 125I-rh-EPO. However, the binding capacity for 125I-rh-EPO in the latter two rats, assessed by an in vitro serum binding study, was lower than for the other eight rats, suggesting that the antibody level in these two was lower. The effect of intravenous preinjection of various volumes of anti-rh-EPO antiserum on the pharmacokinetics of 125I-rh-EPO was examined. The half-life in the beta-phase was prolonged at lower doses of antiserum. When the pretreatment dose of antiserum was further increased, the half-life in the beta-phase rather shortened and the total body clearance (CL(total) increased. These results suggest that repeated administration of rh-EPO induces the production of antibody against rh-EPO that affects the pharmacokinetics of rh-EPO in a biphasic manner; CL(total) was reduced when a small amount of antibody was produced, and CL(total) was increased when a large amount of antibody was produced.
Animals↗
Mechanism for the nonlinear pharmacokinetics of erythropoietin in rats.
The contribution of erythropoietin- (EPO) receptors in target tissues, such as bone marrow and spleen, to the nonlinear pharmacokinetics of recombinant human EPO (rh-EPO) was evaluated in rats. The total body clearance after i.v. administration of rh-EPO (0.2-5 microg/kg) decreased as the dose of rh-EPO increased, approaching a plateau at high doses. The uptake clearance of 125I-rh-EPO by the target tissues, bone marrow and spleen, exhibited clear saturation. The Km values ranged from 240 to 450 pM, which are comparable with the reported value for the dissociation constant of EPO binding to EPO-receptors (180 pM) in rat bone marrow cells. A single s.c. administration of a large dose of rh-EPO (1 microg/kg) caused a reduction in tissue uptake clearance of 125I-rh-EPO by bone marrow and spleen (down-regulation). Furthermore, repeated intravenous injection of rh-EPO caused up-regulation of the tissue uptake clearance of 125I-rh-EPO, especially by the spleen, in a dose-dependent manner. Hematopoietic parameters such as hematocrit and hemoglobin concentration were also increased by repeated rh-EPO treatment and significantly correlated with the sum of the tissue uptake clearances in bone marrow and spleen. These findings suggest that the pharmacological receptor could be an important factor in defining the nonlinear pharmacokinetics of rh-EPO.
Animals↗
Carcinoma of the common bile duct with superficial spread to the intrahepatic segmental bile ducts: a case report.
A 54-year-old woman presented with jaundice. Percutaneous transhepatic biliary drainage, cholangiography via a percutaneous transhepatic biliary, drainage catheter, and percutaneous transhepatic cholangioscopy were performed to alleviate the jaundice and to evaluate her biliary system. A diffuse-type tumor was detected in the common bile duct. The tumor had spread superficially up to the right anterior segmental duct and the left hepatic duct and involved the caudate branches. Curative surgery, which included a right anterior segmentectomy, total caudate lobectomy, and pylorus-preserving pancreatoduodenectomy, was performed. The histopathologic diagnosis was moderately differentiated tubular adenocarcinoma originating at the common bile duct. The extent of the superficial spread of the tumor corresponded to our preoperative determination. Her postoperative recovery was uneventful. In this case report, we discuss the accurate preoperative diagnosis and rational surgical treatment of bile duct carcinoma with superficial spread.
Adenocarcinoma↗
Pharmacokinetic and pharmacodynamic evaluation of central effect of the novel antiallergic agent betotastine besilate.
Betotastine besilate (betotastine CAS 125602-71-3, TAU-284) is a novel antiallergic agent with histamine H1 receptor antagonistic activity. As the classical antihistamines are known to produce drowsiness, the present study was conducted to assess a possible influence of betotastine on the central nervous system (CNS). Measurement of the drug concentration in brain and plasma after i.v. administration revealed that betotastine, as well as cetirizine and epinastine, poorly penetrate into the CNS, while terfenadine do so slightly more and ketotifen remarkably more. In vitro receptor binding assays demonstrated that betotastine is a highly specific histamine H1 receptor ligand, having no significant binding affinity for histamine H3, adrenergic alpha 1, alpha 2, beta, dopamine D2L, serotonin 5-HT2, muscarinic, and benzodiazepine receptors. On global behavior of mice, oral administration of betotastine did not produce any marked changes at the doses of 100-1000 mg/kg, but suppressed huddling behavior at 1000 mg/kg and caused slight mydriasis at 300 mg/kg and more. Betotastine did not significantly affect spontaneous motor activity (SMA) and hexobarbital-induced anesthesia in mice up to 300 mg/kg p.o. In the sleep-wakefulness pattern of cats, it reduced the total duration of sleep at 10 mg/kg p.o., but did not show significant effect at 30 and 100 mg/ kg p.o. Cetirizine showed a similar profile as betotastine in these experiments, whereas ketotifen and epinastine induced sedative signs or toxic symptoms in lower doses, and terfenadine affected SMA and the anesthesia at a high dose. These results suggest the very low liability of betotastine to produce sedative side-effect in a therapeutic dose range.
Animals↗