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Biomedical subjects

K Deguchi

Publications and source records attributed to K Deguchi.

At least 217 records · Page 12Linked to original sources

[Antimicrobial activity of cefetamet against fresh clinical isolates of Branhamella catarrhalis].

Against strains of Branhamella catarrhalis which were separated from various RTIs (respiratory tract infections) in 1991 antimicrobial activities (MICs) of cefetamet (CFMT) were determined, and the following conclusions were obtained. 1. The MIC80 of CFMT against B. catarrhalis was 0.39 microgram/ml, which was higher than that of cefixime (CFIX) by one dilution or twofold, but was lower than that of cefpodoxime (CPDX) by two dilutions or fourfold and that of cefotiam (CTM) by three dilutions or eightfold. 2. The fact that all of the 50 strains tested were beta-lactamase producers appeared to indicate that CFMT was stable against BRO-1 and BRO-2 beta-lactamases produced by B. catarrhalis. 3. Blood concentrations of the test drug, CFMT, and control drugs upon normal single doses were calculated using pharmacokinetic parameters. Lengths of time periods during which drug concentrations stayed above their MICs against B. catarrhalis obtained in this study were determined for CFMT, CFIX, CPDX and CTM. They were, respectively, 12 hours, 12 hours, 6 hours, and 2 hours, thus CFMT appeared to remain above MIC for sufficiently long time for the treatment of RTIs which are affected by B. catarrhalis directly or indirectly.

Cefixime↗

[Antimicrobial activities of ceftriaxone against clinically isolated strains].

Antibiotic activities (MICs) of ceftriaxone (CTRX) against 1,210 strains of bacteria including 28 spp. isolated in 1987 and 1990 were compared with those of other cephems. 1. When compared to data on clinically isolated strains reported in the early 1980s, strains of the following species isolated in 1990 showed extremely elevated MIC90s of CTRX: Staphylococcus spp., Streptococcus pneumoniae, Escherichia coli, Citrobacter spp., Enterobacter spp., Serratia spp., Proteus vulgaris, Morganella morganii and Providencia spp. No changes were observed in MIC90s between the 2 periods for microorganisms such as Streptococcus pyogenes, Haemophilus influenzae, Klebsiella pneumoniae, Proteus mirabilis and Peptostreptococcus spp. 2. The MIC90 of CTRX to S. pneumoniae was high because a large number of benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP) was present among this species. The MIC80 to Bacteroides fragilis group was also high because highly resistant B. fragilis and B. thetaiotaomicron were isolated in large proportions among the bacteria of this group. Other oxime-type cephems also had high MICs against the above mentioned bacteria. Therefore, a further evaluation has to be made with regard to activities of oxime-type cephems such as CTRX against PISP and B. fragilis group. 3. Sample strains included, in high ratios, methicillin-resistant Staphylococcus aureus (MRSA), cephamycin-resistant as well as oxime-type cephem-resistant intestinal bacteria, Gram-negative bacteria, and new-quinolone-resistant bacteria. Some of there resistant bacteria are also CTRX-resistant, and CTRX had insufficient activities against them. 4. With regard to the assessment of changes of frequencies of specific drug-resistant bacteria, including those with CTRX-resistance from year to year, the authors would like to point out the following comment of theirs made in 1989 and 1991, which appears to be increasing its significance, "Subjects of future studies should include dose on the mechanisms for the acquisition of bacterial resistance to entire beta-lactam antibiotics and the social circumstances in which resistant bacteria appear". 5. It appears that those strains resistant to cephems including CTRX are increasingly found among clinically isolated strains in recent years. CTRX, however, was found still effective against most clinical pathogens. Furthermore, considering that CTRX is one of the few drugs which sustain high blood concentrations of active forms we concluded that CTRX is a useful cephem-group antibiotic.

Bacteria↗

Electrophysiological and pharmacological studies of somatosensory reflex myoclonus.

Reflex myoclonus displays symptomatological heterogeneity involving the cortical and brain stem types that seem to originate above the spinal cord. Three cases of generalized myoclonus proved to be spontaneous and stimulus-sensitive, and increased with action. Segmental spinal myoclonus was spontaneous, stimulus-sensitive and rhythmical and decreased with action. Two cases of post-anoxic myoclonus seemed to be of the reticular reflex in which myoclonus was manifested in all muscles, particularly the proximal ones, and for which the EEG showed no spikes preceding myoclonus. The evoked electromyogram showed a long-loop reflex (LLR) of high amplitude, with no giant somatosensory evoked potential (SEP). Pharmacological examinations showed that the thyrotropin-releasing hormone (TRH) enhanced the onset of myoclonus, shortened the latency of the LLR and increased its amplitude, but caused no remarkable changes in SEP. These results indicate that TRH stimulates the medullary reticular neuron, thereby enhancing reticular reflex myoclonus. The myoclonus of a 3rd case was believed to be cortical reflex myoclonus on the basis of the emergence of giant SEP, increased LLR and the onset of spikes in the EEGs preceding myoclonic jerks, as ascertained by jerk-locked averaging analysis with muscular discharge. Pharmacologically, LLR, SEP and myoclonus showed no definite changes in response to TRH. Segmental myoclonus which seemed to have a spinal origin, showed no giant SEP, enhanced LLR or cortical spikes in the electrophysiological studies. No definite clinical or electrophysiological changes in response to TRH were observed. We believe the TRH administration test may be useful in the differential diagnosis of stimulus-sensitive myoclonus. In addition, the origins and nature of these types of reflex myoclonus are discussed.

Acoustic Stimulation↗

Homozygous protein C deficiency: identification of a novel missense mutation that causes impaired secretion of the mutant protein C.

We analyzed the promoter region and all the coding exons and exon-intron boundaries of the protein C gene in a Japanese patient with recurrent thromboembolism and complete protein C deficiency. By sequencing these fragments we identified a previously undescribed mutation. A guanine residue was replaced by an adenine residue converting Gly-292 (GGC) to Ser (AGC) in the last exon coding for the catalytic domain. Substitution of this key amino acid, invariably conserved in the serine protease superfamily to which protein C belongs, probably leads to destabilization of the tertiary structure. In a transient expression assay with COS 7 cells, the protein C level was extremely low in the culture medium of the cells transfected with the mutated protein C expression vector, as compared with the normal vector. In contrast, the cell extracts contained similar amounts of mutant and normal protein C, suggesting impaired secretion of the mutant protein C. Using mutagenic primers to introduce a new PvuII site into the mutant allele, we made a study of the family members in this patient's pedigree, revealing that the mutant allele had been inherited in the affected individuals in this pedigree.

Adult↗

[Study on fibrinolysis and platelet function].

The aim of this study is to evaluate the relationship between tissue plasminogen activator (tPA)/PA inhibitor (PAI) complex and PAI, and platelet in the circulating blood. tPA/PAI complex and active PAI (act PAI; Teijin Co., Japan), and PAI antigen (PAI ant; Biopool AB, Sweden) were assayed by enzyme immunoassay (EIA). The mean concentrations (ng/10(9) platelets) in supernatant from lysate of platelet rich plasma (PRP) and washed platelets were 27.1 +/- 9.2, 1.5 +/- 1.2 in tPA/PAI complex, 188.7 +/- 46.1, 83.3 +/- 7.5 in act PAI and 236.2 +/- 41.6, 191.9 +/- 45.1 in PAI ant, respectively. PRP was mixed with ADP (10(-5), 10(-4), 10(-3) M), for 3 min and the supernatant after centrifugation then was provided for assay of PAI and tPA/PAI complex. Concentrations of act PAI, PAI ant and tPA/PAI complex dose-dependently increased with ADP. Almost the same results were obtained, when collagen and other agents were used instead of ADP. This study revealed that platelets contained quantities PAI (as free PAI) and released PAI during aggregation, and that a part of the PAI immediately formed a complex with tPA. Those findings suggested that platelets may play an important role on the formation of thrombus, in the way of anti-fibrinolysis, in addition to novel platelet functions, such as aggregation.

Adult↗

Plasma level of IL-1 beta in disseminated intravascular coagulation.

The plasma level of interleukin-1 beta (IL-1 beta) was determined in normal individuals, patients with disseminated intravascular coagulation (DIC), patients in the pre-DIC period (within 7 days before the onset of DIC), and non-DIC patients to examine the relationship between DIC and the plasma IL-1 beta level. The plasma IL-1 beta level was 0-0.085 ng/ml in normal individuals, with little difference being seen according to related age. It was significantly higher in the DIC group (0.19 +/- 0.19 ng/ml) than in the pre-DIC group (0.05 +/- 0.08 ng/ml) or the non-DIC group (0.09 +/- 0.01 ng/ml). The plasma IL-1 beta level was not markedly elevated in leukemia patients, even in the DIC group, but it was significantly increased in the DIC group of solid cancer patients and was generally elevated in patients with sepsis. It was markedly elevated to 0.39 +/- 0.26 ng/ml in patients with organ failure. When mononuclear cells were incubated with lipopolysaccharide, it was found that IL-1 beta, tumor necrosis factor, and tissue factor (TF) were released into the medium, and there was an increase of TF release from endothelial cells incubated with this medium. These results suggest that the increase in IL-1 beta reflected the activation of monocytes and may be an important factor in DIC and its associated organ failure.

Adult↗

Dynamic fluctuations in blood of thrombin/antithrombin III complex (TAT).

The dynamic fluctuation of thrombin-antithrombin III complex (TAT) was studied in blood obtained during the daytime (at 9 AM, noon, 3 PM), during extracorporeal circulation and during the course of disseminated intravascular coagulation (DIC), to certify whether the level of TAT in blood can reflect the generation of thrombin. In 10 healthy male volunteers, the mean values of TAT (micrograms/liter) were 1.74 (+/- 1.36) at 9 AM, 1.22 (+/- 0.47) at noon, and 1.25 (+/- 0.68) at 3 PM. TAT did not show a daytime fluctuation, unlike fibrinolytic factors. The mean values of TAT in 38 hemodialyzed patients were 4.83 (+/- 2.8) before the initiation, 6.59 (+/- 4.39) in the first hour, and 13.42 (+/- 10.96) at the end of a dialysis session. In 20 patients undergoing open heart surgery, the mean value of TAT was increased during cardiopulmonary bypass (CPB) and decreased with time after the end of surgery. The fibrinopeptide A (FPA) value was increased with TAT during CPB but achieved a maximum level immediately after heparin neutralization by protamine. In 20 patients with DIC, the values of TAT varied from 5.8 to 297 micrograms/liter in the blood at the onset of DIC. In seven of eight patients treated with low-molecular-weight heparin (LMW-H), the values of TAT and FPA were lower 24 hr after LMW-H than before the treatment. These results suggest that the level of TAT in blood reflected the formation of thrombin and could serve as a sensitive parameter of activated coagulation in circulating blood.

Adult↗

[A study on the beta-lactamase production for Neisseria gonorrhoeae and the sensitivity to various antibacterial agents].

During the 10-year period from 1980 through 1989 using gonococci isolated in Sapporo, we studied beta-lactamase production capacity and the sensitivity of various antibacterial agents and obtained the following results. 1. The frequency of isolating beta-lactamase producing gonococci (PPNG) displayed a gradual tendency to increase during the first half of the 80's and reached a peak in 1985 of 23.9% (61/255). However, thereafter it tended to decline and in 1989 it was 6.3% (2/32). 2. The sensitivity to penicillin-type antibacterial agents was higher against PPNG than non-PPNG against PCG, ABPC, and AMPC displaying about a 7 level MIC90 so that it was quite sensitive. Against CVA/AMPC, SBTPC it showed a relatively favorable MIC90. Also, the sensitivity of PPNG against AMPC with 1984 as the boundary, thereafter the MIC distribution was observed to decline somewhat. 3. Against the monobactam-type injectable drug, AZT, both non-PPNG and PPNG showed a low MIC distribution and against SPCM both showed a relatively high MIC distribution of 3.13-25 micrograms/ml. 4. In regard to the sensitivity to cephem-type antibacterial agents, against such 3rd generation injectables as CZX, CFTM-PI, etc. it displayed a particularly low MIC distribution. 5. Against tetracycline and macrolide antibacterial agents, it displayed a relatively high MIC distribution. 6. Against new quinolone type antibacterial agents, regardless of being non-PPNG or PPNG, it showed a low MIC.

Anti-Bacterial Agents↗

[Plasma thrombomodulin levels in elderly subjects].

Plasma levels of thrombomodulin (TM), fibrinogen, antithrombin III (ATIII) and thrombin ATIII complex (TAT) were studied in healthy young subjects (group A), healthy elderly subjects (group B) and patients with level of TM in group B tended to be higher than that in group A. Levels of TM, fibrinogen and TAT in group C suggested the presence of a hypercoagulable state. When group C was further divided into those with and without diabetes mellitus (DM), the TM level in the former tended to be higher than that in the latter. Furthermore, among the patients with DM, those with diabetic retinopathy showed significantly higher levels of TM than those without retinopathy. Thus, high TM levels indicate the presence of endothelial injury. In groups B and C, TM correlated positively with fibrinogen, and negatively with ATIII, which also indicates that a high TM level is related to a hypercoagulable state. In conclusion, the TM level is considered to be a potential marker of the presence of endothelial injury.

Adult↗

[Biological types and drug-sensitivities of multiple strains of freshly isolated methicillin-resistant Staphylococcus aureus].

Biological studies were done on numbers of methicillin-resistant strains of Staphylococcus aureus (MRSA) either clinically isolated at medical institutes nationwide and sent to us or isolated and identified by us from samples obtained in the year 1990 from patients with various infections. The results of the studies are summarized as follows. 1. The origins of the 1,047 strains used in our studies included arterial and venous blood samples (6.9%), samples from the respiratory tract (43.3%), surgical and dermatological samples (30.2%), otorhinolaryngological and ophthalmological samples (3.8%), urological samples (7.2%), fecal samples (5.1%) and others (3.6%), thus samples from the respiratory tract were the most frequent. 2. The strains were classified according to coagulase types into type II (76.4%), type III (2.1%), type IV (15.4%), type VII (5.3%) and other types (0.8%), thus type II strains were the most numerous. When classified according to their origins, type II strains were found in a significantly high frequency in respiratory tract samples, and type IV strains appeared to be present at relatively high frequencies in the surgical, dermatological, otorhinolaryngological and ophthalmological samples. Some coagulase types were found more frequently in samples from some institutes than in others, but coagulase type distributions were similar in different localities. 3. The strains were classified according to their enterotoxin types into type A (22.8%), type B (10.5%), type C (54.9%) and other types (11.7%), thus type C strains were the most frequent. Significant correlations were observed between enterotoxin type C and coagulase type II, and type A and type IV. 4. Defining strains with minimum inhibitory concentrations (MICs) of greater than or equal to 100 micrograms/ml as high MRSA and less than or equal to 50 micrograms/ml as moderate MRSA, 94.8% of coagulase type II strains were high MRSA and 78.9% of coagulase type IV strains were moderate MRSA, thus coagulase type II strains tended to be high in methicillin resistance. 5. MIC50 and MIC90 of vancomycin (VCM) against many of these strains of MRSA were 0.78 and 1.56 micrograms/ml, respectively, suggesting that VCM has also a potent antibacterial activity against recent isolates of MRSA in Japan.

Cefamandole↗

[Synergistic action of cefodizime and other antimicrobial agents on clinically isolated microorganisms. I. Synergistic action with minocycline].

Since cefodizime (CDZM) shows a broad antimicrobial spectrum and relatively long half life in blood, we examined its synergistic action with minocycline (MINO) in vitro against Staphylococcus aureus. 1. CDZM in the presence of MINO, most of cases 1 MIC showed FIC index greater than 0.5-less than or equal to 2 against methicillin-susceptible S. aureus (MSSA), thus the results suggested a synergistic action against S. aureus. 2. CDZM in combination with MINO at 1 MIC or sub MIC where therapeutically a favorable efficacy is expected on MINO-susceptible strains exhibited FIC index less than or equal to 0.5-less than or equal to 1, Methicillin-resistant S. aureus (MRSA), thus suggesting a synergistic action against MINO-susceptible MRSA strains. Synergism was hardly recognized against MINO-resistant MRSA strains, however. 3. Synergism by both drugs was produced in MINO-susceptible strains of S. aureus including MRSA where MIC by CDZM was high or moderate, but no synergism was demonstrated against MINO-resistant strains. That is, synergistic action by both drugs was thought to depend on antimicrobial activity of MINO.

Cefotaxime↗

[Clinical application of laboratory diagnosis: leukemia and DIC].

Plasma levels of molecular markers of hemostatic activation were investigated in 205 samples from patients with haematopoietic malignancies. These markers included thrombin/antithrombin III complex (TAT), D-dimer, plasmin/alpha 2plasmin inhibitor complex (PIC) and thrombomodulin (TM), and were assayed by EIA methods. Samples were divided into 4 groups according to the level of FDP: group A; FDP 10 greater than, group B; 10 less than or equal to less than 20 group C; 20 less than or equal to less than 40, and group D; less than 40. The mean level of each marker except TM increased in the order of group A, B, C and D. However, in many samples belonging to group A the plasma TAT or PIC levels and both were increased in spite of low FDP level. Furthermore, levels of TAT and PIC in several samples belonging to groups C and D were within the normal range. Also, the mean levels of each marker except TM increased in the order of 2, 3, 4, 5 and over 6 points in DIC score according to the criteria of DIC diagnosis by the research committee on DIC of the Ministry of Health and Welfare in Japan. Eight of the 11 samples (72.7%) obtained from cases with a DIC score of 3 points had high plasma levels of TAT, PIC and D-dimer. Plasma levels of these markers were increased after chemotherapy. These findings lead to the following conclusions: 1) FDP reflexed activation of coagulation and fibrinolysis, but 2) FDP was not more sensitive than TAT and PIC, and 3) the increase of FDP rarely resulted from fibrinogenolysis or non-plasmin mediated fibrinolysis. Furthermore, 4) TAT, D-dimer and PIC may serve as sensitive parameters of hemostatic activation in circulating blood and be valuable markers for early diagnosis of DIC.

Antifibrinolytic Agents↗

[Combined antibacterial activity of aztreonam and clindamycin against clinically isolated strains].

It has been reported in some studies that the combination of aztreonam (AZT) and clindamycin (CLDM) have high clinical effectiveness in the treatment of intractable infections. We, therefore, studied combined in vitro antibacterial activity of these 2 compounds using many freshly isolated strains. 1. AZT and CLDM in combination had synergistic effects on Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Haemophilus influenzae, which are sensitive or quasi-sensitive to CLDM, in the presence of CLDM at MIC or sub-MIC. 2. For Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter cloacae, Serratia marcescens, and Pseudomonas aeruginosa, which are not sensitive to CLDM, the 2 drugs in combination showed synergistic effects on some species and additive or slightly additive effects on most species in the presence of CLDM at those concentrations which are usually maintained in blood. 3. The 2 drugs showed no antagonism.

Aztreonam↗

[Clinical evaluation of fleroxacin in gynecological infections].

Fleroxacin (FLRX), a new quinolone oral antibacterial agent, was studied in the field of obstetrics and gynecology, and the following results were obtained. 1. Clinical efficacy was evaluated in 105 patients (intrauterine infection 38, adnexitis 28, extragenital organ infection 29, others 10), with an exclusion of 9 patients out of a total of 114 patients. FLRX was orally administered at 200 mg or 300 mg once daily. 2. Clinical efficacy rates were 37/38 (97.4%) in intrauterine infection, 26/28 (92.9%) in adnexitis, 29/29 (100%) in extragenital organ infection and 10/10 (100%) in others. 3. Efficacy rates classified by isolated organisms were 23/23 (100%) in single infections by Gram-positive organisms, 11/13 (84.6%) in those by Gram-negative organisms, 8/9 (88.9%) in those by anaerobic organisms and 15/19 (78.9%) in mixed infections. 4. Side effects were observed in 4 cases (3.5%); gastrointestinal disorder with diarrhea and diarrhea in 1 patient each and insomnia in 2 patients. In laboratory examination, eosinophilia and elevation of GOT and GPT were noted in 1 patient each (1.9%). Based on the above results, we consider that FLRX is a useful drug for the obstetrical and gynecological infections.

Administration, Oral↗

[Bacteriological study on fosfomycin against organisms clinically isolated from paranasal sinusitis].

Multi-center bacteriological and clinical studies on fosfomycin (FOM) nasal solution were performed in subjects with paranasal sinusitis from January, 1988 to May, 1990. In these studies, we were exclusively responsible for bacterial isolation from clinical sources, bacterial identification and the determination of drug susceptibility. Before local administration of FOM nasal solution, many strains of various bacterial species were isolated from sources totalling 396 cases involved in phase II clinical studies, dose-finding and open clinical studies. From antibacterial activities of FOM against those isolates, we obtained the following conclusions. 1. Among the 447 isolates, Streptococcus spp. occupied 25.7%, Staphylococcus spp. 21.7% and anaerobic Gram-positive cocci (GPC) 13.6%, showing high detection frequency of aerobic and anaerobic GPC. Next to these, Haemophilus influenzae, Pseudomonas aeruginosa, Klebsiella spp. and Branhamella catarrhalis also were often obtained. 2. After exclusion of possibly contaminating strains which might have entered into cultures at samplings or transfers, the MIC50 and the MIC80 of FOM against the remaining 354 isolates were determined to be 12.5 and 25 micrograms/ml, respectively, indicating that local use of FOM would be fully effective to eradicate most of the bacteria. 3. FOM nasal solution showed sufficient eradication efficacy against most clinical isolates of possible causative organisms of paranasal sinusitis, and appeared to be useful as a topical preparation for the treatment of this disease.

Administration, Intranasal↗

[Antimicrobial activity of cefpiramide to fresh clinical isolates].

In the subjects of 835 strains of 37 clinically isolated microbial strains, which were separated and identified among materials collected from patients with various infections and which were sent from medical therapeutic institutions throughout Japan in 1990, for the purpose of examining the antimicrobial activity of cefpiramide (CPM), its minimum inhibitory concentration (MIC), together with those of other cephem antibiotics, was determined, and the following conclusions were obtained. 1. Microbial strains in which no CPM-resistant strains emerged were Streptococcus pyogenes, Streptococcus pneumoniae and Anaerobic Gram-positive cocci. 2. In comparison with reports by many researchers at the former half of the 1980s, microbial stains suggesting an increase in resistance to CPM were Staphylococcus aureus, Proteus vulgaris, Pseudomonas aeruginosa, Pseudomonas cepacia, Pseudomonas putida, Acinetobacter calcoaceticus, and Haemophilus influenzae, but also in other microbial strains the resistance to CPM was observed in high ratios. 3. Among strains used in the test, methicillin-resistant S. aureus, cephamycin and oxime type cephalosporin-resistant Gram-negative bacilli of Enterobacteriaceae, and new quinolone-resistant microbes were observed in high ratios; therefore, it was considered that CPM could not exert sufficient antimicrobial activities to these strains because of many resistant strains being complicated among these "CPM-resistant strains". 4. It was discussed that "the resistance mechanism observed throughout beta-lactam drugs as a while and the study themes in the dimension including social circumstances where resistant strains emerged", as pointed out by the authors in 1989, increased the significance of these days in the evaluation of timecourse changes in microbes resistant to specific drugs including CPM. 5. There are many unfavorable conditions in the antimicrobial activities of CPM to clinically isolated strains in recent years. However, it was jointly confirmed that CPM maintained effective antimicrobial activities to the majority of clinically isolated strains. Furthermore, when it was additionally considered that CPM was one of not many cephem drugs having persistent blood levels, a conclusion was drawn that CPM was one of clincally useful cephem drugs even at present.

Anti-Bacterial Agents↗