[Estimation of medroxyprogesterone acetate (MPA) and etoposide against a human uterine endometrial cancer].
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Biomedical subjects
Publications and source records attributed to J Yasuda.
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A case of Klippel-Trenaunay-Weber syndrome associated with multiple intracranial angiomas was reported. Intracranial angiomas with Klippel-Trenaunay-Weber syndrome is very rare. Only 4 cases are known to this day. A 24-year-old man fell at his workplace and suffered a head injury. He was admitted to our hospital. Neurological examination revealed no abnormality. However, physiological examination demonstrated hyperplasia and cutaneous hemangiomas of left lower leg, malformation of the left eyelid and clouding of the left cornea. CT showed left hemispheric atrophy and subdural effusion. MRI demonstrated multiple flow voids at the left cerebellar hemisphere and at pons. Cerebral angiogram demonstrated left cerebellar AVM and pontine angioma. Feeding arteries of the AVM were left superior cerebellar artery and left posterior inferior cerebellar artery. Those of the pontine angioma could not be identified. No spinal angiomas were revealed. While spinal angiomas associated with this syndrome are known, association of intracranial lesions are rare. Reported anomalies are angiomas, hemi-hypertrophy of skull and brain, carotid occlusion, megadolicoanomaly of the basilar artery, meningioma and glioma. Our case report with cerebral angiomas is the first one in Japan. We postulate that anomaly of our case originated at the Streeter's 2nd-3rd stage or that multiple anomalies occurred. We emphasize that intracranial, spinal or visceral angiomas, which can be fatal if it bleeds, should be routinely examined in Klippel-Trenaunay-Weber syndrome.
For better understanding of pathophysiological aspects of tuberculosis sequelae, we investigated the relationship between pulmonary hemodynamics and chest X-ray findings. One hundred and seven patients with sequelae of pulmonary tuberculosis were examined by the right cardiac catheterization, and pulmonary hemodynamic values were measured and calculated. Chest X-ray findings were defined and classified into the following five items. The items were emphysematous change; fibrosis, bronchiectasis and/or cavity (hereafter abbreviated as "fibrosis"); pulmonary resection and/or atelectasis; pleural thickening; and thoracoplasty. The extent of each finding was defined. We tried to describe chest X-ray findings by applying and categorizing these classifications and the extent to each case. First, we tried to estimate the grade of pulmonary hypertension by categorized X-ray findings. Further, we analyzed what kinds of findings were most influential on the increase of pulmonary artery mean pressure (PPA) and pulmonary arteriolar resistance (PAR). Secondly, we investigated whether PPA, cardiac index (CI) and PAR changed before and after oxygen administration. Thirdly, we analyzed what kind of X-ray findings most affected pulmonary hemodynamics under 100% oxygen administration for 10 minutes. The results were as follows: (1) Out of 107 cases, it was possible to predict PPA by categorized chest X-ray findings in 75 cases by Hayashi's first method of quantification, one of multivariative analyses. "Pleural thickening" was the most influential finding on the increase of PPA. "Fibrosis" was the most influential on the increase of PAR. (2) The values of PPA, CI and PAR decreased more after 100% oxygen administration than under room air breathing. Therefore, PAR was used as the index to estimate pulmonary hemodynamics under the condition of oxygen administration. (3) It was possible to measure PAR under oxygen administration (PARO2) in 72 cases. "Emphysematous change" was the most influential X-ray finding on the increase of PARO2. From these results, it was thought that pulmonary circulatory disorder in patients with tuberculosis sequelae was caused by the combination of various chest X-ray findings with the different extent. It was possible to predict pulmonary hypertension to a certain degree from categorized chest X-ray findings. It was suggested that "emphysematous change" less related to hypoxic pulmonary vasoconstriction than "fibrosis" and "pleural thickening" from the results of comparison among the partial correlation coefficients, which were associated with the increase of PAR under room air breathing and oxygen administration.(ABSTRACT TRUNCATED AT 400 WORDS)
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Twenty-eight COPD patients underwent right heart catheterization while in clinically stable condition. Pulmonary vascular response to oxygen was evaluated by the percent change in pulmonary arteriolar resistance after 100% oxygen inhalation (% delta PAR), and its relation to the pressure-flow relationship during incremental exercise was assessed. Mean pulmonary arterial pressure (PPA) during exercise was plotted against the cardiac index (C.I.) from rest to maximal exercise in each patient. In most of the patients, the changes in PPA were nearly linear to the C.I. Therefore, a slope could be obtained from the regression equation in each patient. Patients were divided into two groups according to whether their % delta PAR was greater than 20 defined as a responder (RES), or less than five defined as a non-responder (N-RES). Seven out of 28 patients were RES, nine were N-RES, RES showed a higher %FEV1.0 level, C.I. and stroke volume index (S.I.) at maximal exercise, and a lower level of RV/TLC as well as slope. The slope correlated significantly with %DLCO (r = -0.724, p < 0.01), baseline PAR (r = 0.562, p < 0.01) and % delta PAR (r = -0.522, p < 0.01). These results suggest that the diminished pulmonary vascular bed, and the distensibility of pulmonary vessels, appear to contribute to the steepness of the slope and reduced % delta PAR in patients with COPD.
The NS2 protein, one of the two nonstructural proteins of influenza A virus, was found to exist in virus particles. By immunochemical method, the average number of NS2 in a virus particle was estimated to be 130-200 molecules. After solubilization of viral envelope, NS2 was still associated with ribonucleoprotein cores, but was later dissociated upon removal of the M1 protein. A filter-binding assay in vitro indicated direct protein-protein contact between M1 and NS2. Following chemical cleavage of the M1 protein, NS2 bound only a C-terminal fragment of M1. By immunoprecipitation, NS2-M1 complexes were also detected in virus-infected cell lysates. These observations altogether indicate specific molecular association between M1 and NS2. Biological significance of M1-NS2 interaction is discussed.
Influenza virus A/WSN/33 forms large plaques (> 3 mm diameter) on MDCK cells whereas A/Aichi/2/68 forms only small plaques (< 1 mm diameter). Fast growing reassortants (AWM), isolated by mixed infection of MDCK cells with these two virus strains in the presence of anti-WSN antibodies, all carried the M gene from WSN. On MDCK cells, these reassortants produced progeny viruses as rapidly as did WSN, and the virus yield was as high as Aichi. The fast-growing reassortants overcame the growth inhibitory effect of lignins. Pulse-labeling experiments at various times after virus infection showed that the reassortant AWM started to synthesize viral proteins earlier than Aichi. Taken together, we conclude that upon infecting MDCK cells, the reassortant viruses advance rapidly into the growth cycle, thereby leading to an elevated level of progeny viruses in the early period of infection. Possible mechanisms of the M gene involvement in the determination of virus growth rate are discussed, in connection with multiple functions of the M proteins.
Pharmacokinetic and clinical studies on DQ-2556, a new cephem antibiotic, in obstetrics and gynecology were performed and following results were obtained. Concentrations of DQ-2556 were determined in serum, internal genital organs and retroperitoneal exudate after single intravenous administration (i.v.) or drip infusion (d.i.v.) of 1.0 g. Serum levels following i.v. were approximately 30 micrograms/ml at 1 hour, 14 micrograms/ml at 3 hours 30 minutes, and concentrations in internal genital organs including oviduct, ovary, endometrium, myometrium, cervix uteri and portio vaginalis reached approximately 50% to 70% levels of serum concentration. The mean concentration (n = 6) in the retroperitoneal exudate after d.i.v. of 1.0 g following radical hysterectomy were about 20 micrograms/ml, 23 micrograms/ml, 14 micrograms/ml and 8 micrograms/ml at 1 hour, 2 hours 30 minutes, 4 hours 30 minutes and 6 hours 30 minutes, respectively. In clinical trials, DQ-2556 (2.0 g b.i.d. for daily dose) was given in 5 patients with gynecological infections such as pyometra (1 case), salpingitis (1), retroperitoneal space infection (2), pelvic peritonitis (1). The clinical results were evaluated as good in 3 cases and poor in 2 cases including a case with salpingitis infected by Pseudomonas aeruginosa and the other with pelvic peritonitis caused by Methicillin-resistant Staphylococcus aureus. Bacteriologically, 11 organisms were isolated from patients, and eradication rate was 54.5%. Neither side effect nor abnormal laboratory test result was observed. Thus, DQ-2556 appears to be effective for gynecological infections, and the good results were supported by good penetration of the compound into tissues of internal genital organs and retroperitoneal exudate after i.v. or d.i.v.
Foetal electrocardiograms (ECG) were obtained from 39 of 50 Thoroughbred foaling mares close to delivery. The 50 newborn foals were studied electrocardiographically during their adaptive period, immediately after birth. In 48 foals there were paroxysmal arrhythmias or mixed arrhythmias. The most common arrhythmias were sinus arrhythmias including wandering pacemaker (32/50) and atrial premature contraction (30/50). The others observed were atrial fibrillation (15/50), ventricular premature contraction (10/50), partial atrioventricular block (7/50), ventricular tachycardia (4/50), atrial tachycardia (3/50) and idioventricular rhythm (1/50). The duration of the arrhythmias was approximately 5 min, and in all cases the arrhythmia disappeared within 15 min of birth. From foetal ECG recordings, no indication of the likelihood of neonatal arrhythmias was detected. With the exception of 2 cases, all foals have continued to grow and develop normally. These arrhythmias are considered normal physiological processes in newborn Thoroughbred foals during the adaptive period to extra-uterine life. High vagal tone and hypoxaemia at birth are probably the main contributing factors.
Estradiol 17-sulphate is readily converted to 2-OH or 4-OH estradiol 17-sulphate. The latter two strongly antagonize lipid peroxidation, which may play certain roles during pregnancy, such as pregnancy-induced hypertension. Serum estradiol 17-sulphate during mid and late pregnancy was measured using a direct radioimmunoassay without hydrolysis, and the level increased as pregnancy progressed. The levels in the sixth (20-23 weeks) and tenth months (36-39 weeks) of gestation were 1.42 +/- 0.04 nmol/l (mean +/- SD) and 3.42 +/- 1.09 nmol/l, respectively. The maternal venous levels before and at delivery and in the umbilical veins and artery were 3.38 +/- 0.83, 3.48 +/- 1.53, 4.11 +/- 1.40 and 4.30 +/- 1.81 nmol/l, respectively. The latter two values were slightly higher than the former two. Estradiol 17-sulphate in maternal venous blood began to decrease around delivery. Serum lipid peroxides were measured using the method of Yagi. Estradiol 17-sulphate and lipid peroxides showed a simple regression slope (r = -0.548, p less than 0.05) during late pregnancy. These results suggest that estradiol 17-sulphate may be converted to 2-OH or 4-OH estradiol 17-sulphate, which act as lipid peroxide scavengers during pregnancy.
An 84-year-old woman was admitted to our hospital because of swelling of the cervical lymph nodes and multiple tumorous lesions observed on radiographic studies. Transcutaneous lung biopsy was performed, but necrosis of the tissue was too marked to make a diagnosis. The diagnosis of diffuse large-cell lymphoma was made based on a biopsy of the pretracheal lymph node. During the first two months after admission, the left cervical lymph nodes and most of the pulmonary lesions regressed not withstanding of special treatment for lymphoma. The patient eventually died of generalized peritonitis. At autopsy, metastasis of systemic organs by malignant lymphoma was observed. Most of the lung regions were cicatrized, but clusters of atypical lymphocytes were observed in the necrotic tissue. The tumor in the mucosa of the small intestine showed necrosis, which accounted for the intestinal perforation. The total clinical course after admission was about six months. Spontaneous regression of diffuse large cell lymphoma is rare, and this is the second reported case in Japan.
Medroxyprogesterone acetate (MPA), which is widely used clinically as an anticancer steroid preparation, is a very useful drug that seldom causes severe side effects such as bone marrow suppression, and can be dispensed at the outpatient clinic for an oral administration at home to the advantage of QOL. Recently however, there have been several reports suggesting its relationship with thrombosis. We measured t-PA, protein C, factor X, AT III, TAT, plasminogen, PIC, fibrinogen, and D-dimer in 11 patients with gynecologic malignancies who are treated with MPA (600 mg/day) and 11 controls. Then we examined the effects of the drug on blood coagulation and fibrinolytic activities. No changes in these parameters clearly suggested thrombogenesis in either group at this measurement or during the observation period (17 months at the maximum). The present study found no remarkable abnormalities in the blood coagulation and fibrinolytic activities. Thus, to avoid the use of MPA to patients at risk is considered to be the most important precaution for prevention of thrombosis.
A 27-year old patient was diagnosed as having post-primary hilar lymph node tuberculosis. First being admitted to the hospital with a high fever, a chest x-ray examination revealed a swelling of the left hilar lymph nodes and a sputum smear tested positive for acid-fast bacilli. Neither regular clinical examination or investigation had reported abnormality. The acid-fast bacilli was successfully treated through treatment using INH RFP SM. However, after two months, swelling was observed in the right para-tracheal lymph nodes, Further, a bronchoscopic examination revealed polyp-like tumors at the left upper and lower bifurcation. The swelling of the para-tracheal lymph nodes was considerably reduced and the tumors non-existent after five months. These lymph node reactions could have likely been a part of the so called early exacerbation. The polyp-like tumors were not found during the bronchoscopy performed during admission to the hospital. It is therefore suspected that the cause was perforation of the hilar lymph node into the bronchus.
A previously healthy 16-year-old girl complaining of fever, hemosputum, chest pain and dyspnea was hospitalized. On admission, physical examination revealed mental confusion, holosystolic heart murmur, and swelling of the left foot. Laboratory investigations showed anemia, leukocytosis, thrombocytopenia, activation of inflammatory reactions, prolongation of PT and APTT, and hypoxia. Antinuclear antibody test was negative. There were no other findings suggestive of collagen diseases such as SLE. Chest X-ray showed consolidation in the left lower lung field and pleural effusion. Echocardiography disclosed a mass lesion in the left atrium in contact with the mitral valve, and mitral regurgitation. No findings indicative of an infectious etiology were present. The patient rapidly improved with high dose corticosteroid and anticoagulant therapy. A venogram of the lower extremity disclosed deep venous thrombosis. A lung ventilation-perfusion scan revealed multiple pulmonary thromboemboli. Elevation of anticardiolipin antibody was noted. Based on these findings, the diagnosis of primary antiphospholipid syndrome was made. Further administration of steroid and anticoagulant resulted in decrease of the titer of anticardiolipin antibody. This is the second report of primary antiphospholipid syndrome in Japan. The clinical significance of this disease is also discussed.
The haemagglutinins (HAs) of five H3 influenza A viruses isolated from domestic ducks and one from a goose in southern China were analysed antigenically and genetically. The patterns of reactivity of two of the duck viruses and the goose virus with a panel of monoclonal antibodies to 10 different epitopes on the H3 HA were similar to those of influenza viruses isolated from wild ducks and pigs, as well as those of the earliest human H3 viruses. The other three isolates from domestic ducks were different from each other and from these viruses antigenically. Sequence analysis revealed that the HA genes of the two duck viruses and the goose virus were closely related to those of isolates from wild ducks and pigs; the identities between the deduced amino acid sequence of the HA of one of the isolates from domestic ducks and those of isolates from a wild duck and a pig were 98.7% and 99.5%, respectively. The antigenic and genetic similarity between these H3 HAs suggests that in southern China, the hypothetical influenza epicentre, domestic ducks may have played a role in the introduction of avian influenza viruses to pigs from feral ducks. The findings also support the hypothesis that the pig was a 'mixing vessel', producing a new human pandemic strain, A/Hong Kong/68 (H3N2), by genetic reassortment.
Between 1986 and 1990 we had twelve patients (ten males, two females, 19-65 years of age) with laryngeal tuberculosis who complained hoarseness and whose larynges were examined by fiberscopes. Chest roentgenograms revealed cavities in ten and in seven the lesions were extensive (Grade 3 according to the classification of Japanese Society for Tuberculosis). In all patients sputum smears were positive. Both patient's and doctor's delays were longer than those of patients with pulmonary tuberculosis without laryngeal involvements. Group infection was the source of infection in one patient. Since the diagnosis of laryngeal tuberculosis is difficult to make on clinical basis, it is important to make fiberscopic examinations of the larynx and do biopsies in patients with pulmonary tuberculosis who complain hoarseness.
In 101 newborn Thoroughbred foals and foaling mares, 45 fetal (FECGs) and 101 neonatal electrocardiograms (NECGs) were obtained to investigate neonatal arrhythmias and other parameters including changes in fetal (FHR) and neonatal heart rate (NHR). Moreover, umbilical arterial, venous and jugular venous blood gas tensions and pH immediately after birth were analyzed to compare with the type and the degree of neonatal arrhythmias. Before delivery, in 37 fetuses FHR gradually decreased while in 8 cases it increased after rupture of the chorio-allantois. Abnormal deliveries were related in 5 of the 8 cases. In foals born with sinus rhythm, NHR at birth was 22 beats per minute higher than the FHR immediately before birth, gradually decreased for 1-2 min and then increased. Various types of neonatal arrhythmias and their combinations were recorded in 92 of the 101 NECGs. No arrhythmias demonstrated in NECGs were detected in the FECGs. The mean values for umbilical arterial pH, PCO2 and PO2 indicated that newborn foals at birth were exposed to hypoxemic, hypercapnic and acidemic conditions. The relationship between the umbilical arterial PO2 value as an indicator of the degree of hypoxemia of the foal and the type of arrhythmias was not apparent. However, the PO2 value in the group with severe arrhythmias was comparatively lower than that in the group with mild arrhythmias. It was suggested that hypoxemia played an important role in neonatal arrhythmias.
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