Biomedical subjects
Publications and source records attributed to T Nishi.
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A survey has been made of 150 cases of acute renal failure (A.R.F.) seen between 1962 and 1981. The overall mortality was 43.3%. The patients ranged from 7 to 75 years old. The mean age of all the patients was 47.2 years old. The mean age of the patients seen between 1970 and 1981 was 58.1 years old, 20 years older than those seen between 1962 and 1969. Despite increasing expertise in management of the complications of surgical, medical, and obstetric disorders, and considerable technical advances in dialysis, there was no decrease in mortality over the 20-year period of survey. Many factors have been identified as having an adverse influence on prognosis, such as age of patient, surgical origin, and complications. Mortality rate was high in the patients over 71 years old, postsurgical group (55.6%), and hepatorenal syndrome group (92.3%). Five major complications had an adverse influence: septicemia (57.1%), respiratory infection (61.1%), cardiovascular disorder (46.3%), hemorrhage (59.6%), unconsciousness (62.2%), and hepatic dysfunction (56.8%). Between 1970 and 1981 the mortality in the patients dialyzed up to 3 times was 81.3%, compared with 26.5% in those dialyzed from 4 to 19 times (p less than 0.01). In the former group severity of the underlying disorder had an adverse influence on prognosis. Although the A.R.F. may be controlled in the earlier stages of illness, many of these patients die of overwhelming infection or other complications.
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The TNM classifications of neuroblastoma, nephroblastoma and soft tissue sarcoma were adopted at the International Conference for TNM Classification (UICC) held in May 1980. There is no TNM system under contemplation, however, for primary liver carcinoma in childhood. Accordingly, we have formulated the proposed Japanese TNM system for this carcinoma in children and examined its validity in 136 cases of hepatoblastoma seen in the listed 14 institutions. The basic policy of the Committee on the Japanese TNM Classification is not to include the resectability of the tumor and regional lymph nodes or any other status of the disease resulting from therapeutic intervention as a component of the pTNM system. This is a feature which makes our proposed system widely divergent from the accepted classification scheme for the three types of tumor cited above.
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The tumor promoter teleocidin inhibited the proliferation of human HUH hepatoma cells in tissue culture. HUH cells cultured with teleocidin developed elongated cytoplasm. In addition, these biological effects of teleocidin were associated with a remarkable decrease in the amount of cellular fibronectin. The synthesis of structural proteins and the number of cell surface receptors for epidermal growth factor were not altered in cells treated with teleocidin, suggesting that teleocidin acted selectively on some of the cellular constituents such as fibronectin. The present data also suggest a possible relationship between the cellular fibronectin content and the biological characters of HUH cells.
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The effectiveness of magnesium solution in protecting ischemic myocardium was evaluated in a blood-perfused, isolated rabbit papillary muscle preparation. Anoxic cardioplegia was induced by either a control solution containing no magnesium or a test solution containing a magnesium concentration of 160 mEq/L. The magnesium solution induced a very rapid cardiac arrest, less than 1 minute, in contrast to more than 10 minutes with the control solution. Restarting time was not affected by magnesium cardioplegia. Following 30 minutes of anoxic cardioplegia, the magnesium group showed significantly (p less than 0.01) better recovery of myocardial contractility, 91.3% +/- 8.3% (n = 6), than the control group, 77.7% +/- 4.1% (n = 6). These protective effects of magnesium were lost when the ischemic time was longer than 45 minutes.
An 8-year-old boy with anomalous origin of the left coronary artery from the pulmonary artery associated with tetralogy of Fallot, which was definitely diagnosed preoperatively, was operated on with success. Direct implantation of the left coronary artery into the aorta following division of the left coronary artery from the pulmonary artery and, concomitantly, total repair for tetralogy of Fallot using an external valved conduit were performed. Postoperative cineangiogram revealed a hemodynamically well-repaired intracardiac condition and anterograde filling of the left coronary artery, compared with retrograde left coronary flow from intercoronary collateral vessels preoperatively. To the best of our knowledge, there is not a previously published report of anomalous origin of the left coronary artery from the pulmonary artery associated with tetralogy of Fallot that was treated surgically with success.
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The activity of cefmenoxime (SCE-1365), 7 beta-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid, was compared with that of other cephalosporins. Cefmenoxime exhibited high activity against a wide variety of gram-positive and gram-negative bacteria. The in vitro activity of cefmenoxime against Streptococcus pyogenes, Haemophilus influenzae, and Enterobacteriaceae, including indole-positive Proteus, Serratia marcescens, Enterobacter cloacae, and Citrobacter freundii, was 10 to 1,000 times greater than that of several other cephalosporins. Against Pseudomonas aeruginosa, cefmenoxime showed activity two to four times that of sulbenicillin and carbenicillin but less than that of cefsulodin. Variation in pH, addition of horse serum, and type of growth medium had definite effects on the activity of cefmenoxime, and the inoculum size affected the activity against bacterial species. In Escherichia coli cefmenoxime showed marked affinity for penicillin-binding protein 3 (PBP-3), followed by PBP-1 (1A and 1B). This affinity profile was well correlated with its filamentous cell-forming activity under extremely low drug concentrations and with its bactericidal activity against microorganisms. The high in vitro activity of cefmenoxime was reflected in the degree of protection observed in mice infected intraperitoneally with a wide variety of gram-positive and gram-negative bacteria. Furthermore, cefmenoxime showed good therapeutic activity against infection models in mice such as respiratory tract infection caused by Klebsiella pneumoniae and urinary tract infection caused by Proteus mirabilis.
The effect of cefotiam and cefazolin on the ultrastructure of Klebsiella pneumoniae DT-S in vitro and in experimental pneumonia in mice was examined by electron microscopy. The action of both cephalosporins against K. pneumoniae DT-S was bactericidal, and a dose response in the action was definite. At the minimal inhibitory concentration of each cephalosporin, filamentation of the cells was induced and the cytoplasm became sparse during the course of incubation. With elevation of the concentration of the cephalosporins, spheroplasts were formed; they subsequently collapsed. In the lungs of mice, the infecting organisms localized in the alveolar space, and each cell was connected by a threadlike material. A fibrous matrix, located on the cell surface of the infecting organisms, was observed in ultrathin sections. By administration of each cephalosporin to mice, several morphological changes, similar to those noted in vitro, were observed in the infecting organisms.
The MICs of cefotiam and cefazolin against K. pneumoniae DT-S were unaffected by the inoculum size and were 0.1 and 1.56 micrograms/ml, respectively. Bactericidal and bacteriolytic activities of the cephalosporins were more potent in bacterial concentrations of 10(7) colony-forming units (CFU)/ml than in concentrations of 10(8) CFU/ml. Both activities of cefotiam were more markedly influenced by bacterial concentrations than those of cefazolin. Therapeutic activity of cefotiam was about 9 approximately 15 times as potent as that of cefazolin in experimental pneumonia caused by K. pneumoniae DT-S in mice, and this finding was in accordance with the ratio of in vitro antibacterial activities of the two cephalosporins as judged by the MICs or the bactericidal and bacteriolytic activities in bacterial suspension of 10(7) CFU/ml. The range of concentrations of cefotiam which induced cell filamentation in vitro, was wider than that of cefazolin. This difference, however, was not reflected on the therapeutic activities of the two cephalosporins in the model infection. In the pneumonic lungs, definite therapeutic doses of both cephalosporins (80 mg of cefotiam per kg and 640 mg of cefazolin per kg) produced mainly bacteriolysis of the challenge organisms.
Lewis rats were given a single intravenous injection of soluble immune complexes, composed of human serum albumin and rabbit anti-human serum albumin, prepared with either whole antiserum or purified IgG antibodies. The animals were sacrificed at intervals ranging from 2 to 24 hours, and Fc and C3 receptor activities of Kupffer cells were studied in Kupffer cell-enriched suspensions and in frozen sections of liver, using red cell rosetting techniques employing IgGEA and IgMEAC reagents. At 2 to 12 hours, there was reduction or loss of Fc and C3 receptor activity. The extent of reduction correlated with the amount of complexes injected. Both C3 and Fc receptor activity returned to normal levels within 24 hours. Immunofluorescence revealed rabbit IgG in numerous Kupffer cells at 2 hours, but in almost none at 6 to 12 hours after injection. 125I trace-labeled immune complexes were shown to be cleared more slowly than normal in animals injected 2 hours earlier with immune complexes. The findings show that circulating immune complexes can produce loss of Fc and C3 receptor function of Kupffer cells in vivo and provide evidence that this can result in diminished clearance of complexes.
The protective effects of procaine hydrochloride on the anoxic heart were investigated using the papillary muscle contractility of an isolated, blood-perfused rabbit heart as an index of myocardial function. Fifty-four experiments were divided into nine groups of six experiments each, in which anoxic periods (30, 45, 60 minutes) and concentration of procaine (solution 3, 0.3%) were the variables. The hearts arrested significantly faster with solution 3 compared with solution 2 or 1 (p < 0.01). After 30 minutes of anoxia, the recovery of the contractility was 81.1 +/- 4.2% with solution 1, 90.7 +/- 3.4% with solution 2, and 90.6 +/- 3.3% with solution 3. After 45 minutes of anoxia, the recovery was 31.8 +/- 19.0% with control, 67.5 +/- 15.8% with 0.03% procaine, and 58.1 +/- 22.8% with 0.3% procaine. After 60 minutes of anoxia, the recovery was 2.2 +/- 2.7% with control, 18.7 +/- 14.1% with 0.03% procaine, and 5.0 +/- 7.3% with 0.3% procaine. After each anoxic period, the best recovery occurred with those hearts arrested by solution 2. Although the difference in recovery between the procaine groups was not statistically significant, a longer time was required for the hearts arrested with solution 3 to reach full functional recovery. This study indicated that procaine per se has a protective effect on the anoxic hearts and that although high concentration (0.3%) of procaine arrests the heart rapidly, it delays the recovery of contractions. We recommend the use of 0.03% procaine in cardioplegic solution.
Such factors as suspending medium, operating pressure, exposure time, inoculum size, and strain, sex, age, and weight of the animals were examined for their effects on the development of respiratory tract infection with Klebsiella pneumoniae DT-S in mice. The suspending medium was one of the most important factors. Aerosol challenge with a 10(9) colony-forming units per ml resulted in deposition of 10(4) colony-forming units of the organisms in the lung. The numbers of organisms in the lung increased rapidly, and by 30 h, a well-developed pneumonia was apparent. All the mice died within 4 days after infection. The therapeutic effectiveness of single-dose kanamycin regimens decreased markedly with a delay in administration. The effectiveness of multi-dose kanamycin regimens was influenced by the frequency of dosage. Thus a 12-h dosage schedule was superior to a 24-h regimen. Administration of 20 mg of kanamycin per kg at 12-h intervals for 10 days, initiated 30 h after infection, provided a complete cure. The infecting organisms in the lung, trachea, and blood were eradicated by the kanamycin therapy, but those in the nasal cavity were difficult to eliminate.
The efficacies of several dosage schedules, productive of plasma levels of cefotiam and cefazolin of short and long duration and starting at three levels of cefotiam and cefazolin of short and long duration and starting at three different times (3, 18, and 30h) after infection, were examined in experimental pneumonia caused by Klebsiella pneumoniae DT-S in mice. With each of the multiday regimens there was a large segment of the day when plasma levels fell below assayable concentrations. In all cases, cefotiam proved about eight times as active as cefazolin, indicating that the potent in vitro antibacterial activity of cefotiam was well reflected in the therapeutic effect in this model infection. As judged by the total dose administered, the regimen of cefotiam producing a low but sustained plasma level gave better therapeutic effects than that exhibiting a high but transient plasma level. The cefotiam levels in the plasma of mice that received the regimen effective when initiated at 18 h after infection were less than the expected levels in humans after intravenous infusion of the usual clinical dose.