[Disseminated intravascular coagulation (DIC) during cervical laminectomy].
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Biomedical subjects
Publications and source records attributed to T Komatsu.
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Fifty-eight patients studied were anesthetized with diazepam, pancuronium, and a moderate dose of fentanyl; 99 sets of multiple hemodynamic variables were measured after sternotomy and before cardiopulmonary bypass. The relationship between oxygen consumption (VO2) and oxygen delivery (DO2) was studied. The critical value of DO2 was identified to be 330 ml/min X M2 or 8.2 ml/min X kg by an analysis of the regression lines. When DO2 was less than 330 ml/min X M2, the value of VO2 decreased in proportion to a decrease in DO2 and VO2 was expressed as: VO2 = 0.36 X DO2 - 11.20 (n = 30, r = 0.77, p less than 10(-6). At DO2 greater than 330 ml/min X M2, VO2 values plateaued at 109 +/- 16 (SD): n = 69; r = -0.02, p greater than 0.05; while mixed venous oxygen tension (PVO2) decreased in proportion to the decrease in DO2, suggesting compensatory increase of oxygen extraction. A decrease of VO2 at DO2 less than 330 ml/min X M2 suggests tissue oxygen deprivation occurred.
Histopathological analysis of the heart in adult mice inoculated with Coxsackie virus B3 (CB3) strains revealed that strain SK-74 isolated from a patient suffering from severe diarrhea and fever produced severe myocarditis but strain T-70 isolated from a healthy child induced no lesion in the hearts of mice tested, and that intensities of myocardial lesions in mice inoculated with strain PMH were higher than those in mice inoculated with prototype strain Nancy. The results support the conclusion in the preceding paper that strain SK-74 is virulent but strain T-70 is avirulent in mice. The results also partially indicated that the virulence of prototype strain Nancy in the heart of mice is enhanced by passages of the strain in the heart of mice. All four strains of CB3 produced lesions in the pancreas although lesions induced by strain T-70 were less marked than those induced by the remaining three strains.
Virulence of Coxsackie virus B3 (CB3) was compared in mice between strain SK-74 isolated from a patient and strain T-70 isolated from a healthy child as well as between prototype strain Nancy and its mouse-passaged derivative strain PMH. Strain SK-74 showed a high mortality (40-80%), while strain T-70 did not induce deaths in mice (mortality: 0%). Strain PMH showed a high mortality (65-85%), but strain Nancy did not cause deaths in the mice. In agreement with the mortality trend, virus titers in the heart and other organs of mice inoculated with strain SK-74 and PMH were higher than those in mice inoculated with T-70 and Nancy strains. Since virus titers in the heart remained higher than those in other organs, the heart was regarded as the main organ in which CB3 could replicate and induce cell degeneration. The present results suggest that a marked variation in virulence in the hearts of mice among CB3 strains occurred and that passage through the hearts of mice enhances the virulence of CB3 in the hearts of mice.
SM-1652 (sodium 7-[D(-)-alpha-(4-hydroxy-6-methylpyridine-3-carboxamido)-alpha-(4-hydroxyphenyl)acetamido]-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylate) is a new semisynthetic cephalosporin derivative with a broad spectrum of antibacterial activity. Its in vitro activity against gram-positive bacteria was comparable to that of cefazolin. SM-1652 exceeded cefazolin in potency and broadness of antibacterial activity against such Enterobacteriaceae as indole-positive Proteus spp., Enterobacter cloacae, and Serratia marcescens. A remarkable feature of the spectrum of SM-1652 is its high activity against Pseudomonadaceae. Against 200 clinical isolates of Pseudomonas aeruginosa, SM-1652 was significantly more active than cefoperazone, cefotaxime, and sulbenicillin and as active as cefsulodin. The activities of SM-1652 against Pseudomonas maltophilia and Pseudomonas cepacia were superior to those of cefoperazone, cefotaxime, cefsulodin, sulbenicillin, and gentamicin. SM-1652 was relatively stable to hydrolysis with plasmid-mediated penicillinases and cephalosporinases produced by gram-negative bacteria.
The effect of energy on nitrogen balance was examined in young men given amino acid mixture. The minimum amino acid nitrogen requirement for nitrogen equilibrium was determined together with the egg protein requirement. In experiment 1, the nitrogen sparing effect of energy was evaluated in four male students receiving diet containing an amino acid mixture and a constant nitrogen intake of 3.5 g N/day, which was equivalent to the nitrogen requirement with excess energy intake determined by Rose and Wixom (1). When the dietary energy supply was 45 kcal/kg, which is approximately the maintenance level, the mean nitrogen balance was negative, being -23.9 +/- 9.3 mg N/kg. However, with an excess energy intake of 55 kcal/kg, the nitrogen balance improved significantly, being -6.1 +/- 7.7 mg N/kg. In experiment 2, the nitrogen requirement of egg-pattern amino acid mixture for apparently zero balance was evaluated at maintenance energy intake in 28 Japanese young men and was compared with that of egg protein. After receiving standard diet, the subjects were given a semi-purified experimental diet containing egg-pattern amino acid mixture at nitrogen intake levels of 60, 75, 100, and 130 mg N/kg for two weeks. Then all groups except the 60 mg N/kg group were given isonitrogenous egg protein diet for another week. Energy intake was kept constant at approximately the maintenance level of 44.4 +/- 1.4 kcal/kg throughout the experiment. Nitrogen balance was not significantly different in groups given egg-pattern amino acid mixture and intact egg protein in each nitrogen intake level. From regression analysis, the nitrogen requirement for nitrogen equilibrium of the amino acid mixture was calculated to be 110.1 +/- 50.2 mg N/kg, which was not significantly different from the value of 88.4 +/- 40.6 mg N/kg of egg protein. It was concluded that the total amino acid requirement estimated by Rose and Wixom (1) was too low because they gave excess energy, and that there was no difference between the nitrogen requirement of egg protein and that of the corresponding amino acid mixture.
The nutritional quality of soy protein isolate (SPI) was evaluated in young men by the nitrogen balance method using fish protein as a standard. Twenty-one male university students were given SPI (Supro 620, Ralston Purina Co., St. Louis, Mo., U.S.A.), fish protein (cod fish) or a 50:50 mixture of the two proteins as the sole source of protein. SPI and fish were prepared as paste products (kamaboko). Four experimental periods were used in which each subject received 0.35, 0.45, 0.55 and 0.65 g protein/kg/day, respectively, given in random order. Each period consisted of one day on protein-free diet and ten days on the experimental diet, with an interval of three days on a free-choice (ad libitum) diet between periods. Energy intake was constant for each individual to maintain their body weight (44.6 +/- 2.4 kcal/kg/day). The linear regression equations obtained between nitrogen intake (X: mg N/kg/day) and the apparent nitrogen balance (Y: mg N/kg/day) were as follows: SPI, Y = 0.298X-35.2; fish protein, Y = 0.365X-31.8; mixed protein, Y = 0.423X-38.3. The nitrogen requirement for maintenance of nitrogen equilibrium determined from the regression equation was 118.1 +/- 15.4 mg N/kg/day for SPI, 87.1 +/- 17.2 mg N/kg/day for fish protein and 90.5 +/- 17.1 mg N/kg/day for mixed protein. The NPUs calculated at the respective maintenance nitrogen intakes were 38.9, 52.8 and 50.8 for SPI, fish protein and mixed protein, respectively. There was no significant difference between the nutritive values of mixed protein and fish protein. The nutritive value of SPI relative to fish protein was estimated as 82%, 74% and 74% by the slope-ratio method, and values for the nitrogen requirement and NPU, respectively.
The synthesis and the antibacterial activity of 7 beta-[D-2-[(4-hydroxy-1,5-naphthyridine-3-carbonylamino)- and (4-hydroxypyridine-3-carbonylamino)]-2-(4-hydroxyphenyl)acetamido]-cephalosporins with various substituents at the 3-position in the cephem nucleus are described. These compounds exhibited strong antibacterial activities against a variety of Gram-positive and Gram-negative bacteria, including Pseudomonas aeruginosa and Enterobacter aerogenes, which are insensitive to cefazolin and cefmetazole. The compounds (3e, 4e) having a 1-methyl-1H-tetrazolylthiomethyl group at the 3-position appeared to show the best activity in each series. The 4-hydroxypyridine-3-carbonylamino derivative 4e gave higher peak serum concentrations and urinary recovery rates than those of the 4-hydroxy-1,5-naphthyridine derivative 3e when administered subcutaneously to mice and intramuscularly to rats.
The influence of the chirality of the 7-acyl side chain and of various N-acyl moieties (A-CO-) on the in vitro activity of 7 beta-[2-acylamino-2-(4-hydroxyphenyl)acetamido ]-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acids (6) was investigated. A cephalosporin having a 7-acyl side chain of S-configuration (6r) was only weakly active against Staphylococcus aureus and Klebsiella pneumoniae and was inactive against the other species tested. Among the various N-acyl moieties in the cephalosporins having a 7-acyl side chain of the R-configuration, the 4-hydroxypyridine-3-carbonyl moiety, unsubstituted or substituted with 5-bromo and/or 6-alkyl groups and the 4-hydroxy-1,5-naphthyridine-3-carbonyl moiety, unsubstituted or substituted with a 6-methyl and a 6-methoxy group gave the most active compounds. N-Ethylation of the 4-hydroxy-1,5-naphthyridine-3-carbonyl derivative and the 4-hydroxypyridine-3-carbonyl derivative (6p, 6q) resulted in a decrease of the in vitro activity.
The influence of various 3-substituents on the antibacterial activity of 7 beta-[D-2-(4-hydroxy-6-methylpyridine-3-carbonylamino)-2-(4-hydroxyphenyl) acetamido]ceph-3-em-4-carboxylic acids (III) was investigated. Introduction of an acidic substituent, such as a sulfo or a carboxyl group, to a 3-(1-methyl-1H-tetrazolyl)thiomethyl substituent (IIIf--i) resulted in a marked loss of activity against Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus faecalis, Escherichia coli, Klebsiella pneumoniae, and Enterobacter aerogenes, in contrast to an in crease of activity against Proteus mirabilis. Displacement of the acetoxy group of IIIb with pyridines (IIIm--p) enhanced the activity against P. aeruginosa and E. aerogenes: their activity against those strains were superior to that of the cephalosporin IIId having a 3-(1-methyl-1H-tetrazolyl)thiomethyl substituent. As a result of extensive studies in addition to the study of in vitro activity in this series, 7 beta-[D-2-(4-hydroxy-6-methylpyridine-3-carbonylamino)-2-(4-hydroxyphenyl) acetamido]-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid, code No. SM-1652, cefpiramide (generic name), was selected as a candidate for further biological and clinical investigations.
Twenty-three rat lung specimens collected in outbreaks of hemorrhagic fever with renal syndrome (HFRS) in three medical institutions were inoculated onto the VERO-E6 cell monolayers. After several blind passages, an agent growing serially in the cell cultures and reacting specifically with known HFRS-positive sera was isolated from two of these specimens. The two isolates were antigenically identical each other. The agent, named strain SR-11, was identified as the causative virus of HFRS by its antigenic identity with E6 cell-adapted HFRS virus, Hantaan 76-118 strain, and the specific reactions with sera from various HFRS cases.
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A series of antigens was synthesized in which peptide spacers were inserted between the ABA group and TNP-Ficoll. When these antigens were used to assess helper activity in Lewis rats immunized with ABA-tyr, it was found that an increase in the ABA-epitope density and an increase in the peptide spacer size both increased the efficacy of the antigen in eliciting ABA-specific help, manifest by an enhancement of anti-TNP PFC. Substitution of D- for L-amino acids progressively decreased the ability of these conjugates to elicit help until D-tyr-D-ala-D-ala, which when used for coupling ABA to the TNP-Ficoll resulted in a nonimmunogenic molecule. When these same Ficoll conjugates were used to study ABA-specific in vitro proliferative responses, it was found that introduction of even a single D-amino acid into the spacer greatly reduced reactivity. By contrast the ABA-peptides, free of the Ficoll backbone, were all equivalent on a molar basis in their ability to elicit ABA-specific in vitro proliferation, regardless of their content of D-amino acids. These results suggest some form of digestion is required in the processing of these antigens before they can elicit helper activity. This processing can occur only if one or more L-amino acid residues are present. If the ABA-peptides are free of the Ficoll backbone, they are all capable of stimulating T cell proliferation without apparent further processing.
In an effort to study T cell functions in Lewis rats immunized with ABA-N-acetyl-L-tyrosine (ABA-tyr), we developed an antigen that provides a sensitive assay of ABA-specific helper function that is read as an increase in TNP-specific plaque-forming cells (PFC). This antigen has ABA coupled to AECM-Ficoll by virtue of a tripeptide (tyr-ala-ala) spacer and TNP coupled to the AECM side chains. At subimmunogenic doses, this antigen induced 400 anti-TNP PFC/10(6) spleen cells in ABA-tyr-immunized rats. As many as 8000 PFC/10(6) spleen cells were induced with larger doses of antigen (200 micrograms). By contrast, only 490 PFC/10(6) spleen cells could be induced with 1 mg of the conventional doubly haptenated protein carriers such as ABA-BSA-TNP. Both direct and indirect PFC were induced by this antigen in primed rats. The use of this antigen and passive transfer techniques to study ABA-specific helper activity revealed some differences from ABA-specific delayed-type hypersensitivity (DTH) and in vitro proliferation, which were studied previously. Cells responsible for helper activity appeared sooner after immunization and were found most prominently in peritoneal exudates but also significantly in spleen where the cells responsible for DTH or in vitro proliferative responses were never found. By contrast, helper cells were not seen in lymph nodes, where some proliferative activity could be found. Of these three ABA-specific T cell functions, helper activity was least easily suppressed by the previously used regimens of ABA-tyr in incomplete freunds adjuvant (IFA). Moreover, helper activity appears after injection of ABA-tyr in IFA, a method that has never in our hands yielded detectable DTH or in vitro proliferative responses. Despite these differences, phenotyping with monoclonal antibodies indicated that cells responsible for helper and proliferative activities were both W3/25+ and OX8-.
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To detect a biliary tract infection, antibody-coated bacteria (ACB) in bile and duodenal juice was examined in 146 specimens from 111 patients by direct immunofluorescent antibody technique (FA test). One hundred and forty one of these specimens were also cultured and the results were compared with those of FA test. Organisms were isolated in 77 specimens from 59 patients. Thirty nine (from 31 cases) in these 77 specimens showed ACB. Result of FA test was related to clinical findings such as fever and leucocytosis, but was not to upper abdominal pain, jaundice, liver function test abnormality and the presence of gallstones. Isolates were mainly gram negative rods in ACB positive group (77%). Classification of immunoglobulin of ACB indicated a predominance of IgG and IgA classes over IgM class.
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