Biomedical subjects
Publications and source records attributed to S Kohno.
Four patients with laryngotracheoesophageal cleft were treated in our institution. Two of the patients survived and two died. Cleft levels ranged from partial 15 mm laryngotracheoesophageal to total with extended right bronchoesophageal cleft.
The activity of a new macrolide, TE-031 (A-56268), against Legionella pneumophila in vitro was superior to the activities of roxithromycin, erythromycin and josamycin. The tissue concentrations of TE-031 in guinea pigs after oral administration (20 mg/kg) was much higher than those of roxithromycin, erythromycin and josamycin. The maximum concentration of TE-031 was 107.0 mg/kg in the lung, and 1.4 mg/l in the serum. The uptake of macrolides by cells collected by bronchoalveolar lavage in guinea pigs was measured by a radioisotopic method. The maximum ratios of intracellular to extracellular concentration of TE-031, roxithromycin, josamycin and erythromycin were 71.9, 24.8, 39.7 and 7.9, respectively. In infected guinea pigs, with the exception of erythromycin, the ratios were reduced to approximately half the values in normal animals. TE-031 showed greater therapeutic efficacy against experimental L. pneumophila pneumonia than roxithromycin, erythromycin and josamycin. TE-031 is a promising drug for treatment of legionella pneumonia and should be investigated in a clinical study on human Legionnaires' disease.
Five 14C-labelled macrolide antibiotics (erythromycin, josamycin, clarithromycin (TE-031), rokitamycin and roxithromycin) were studied for their transport into human polymorphonuclear leucocytes. Intracellular/extracellular concentration ratios (transport ratios) of these macrolides were quite high: erythromycin, 6.6; josamycin, 15.5; clarithromycin, 16.4; rokitamycin, 30.5; and roxithromycin, 21.9. When polymorphonuclear leucocytes were pre-treated with formaldehyde or incubated at 4 degrees C, or at low pH, transport ratios were reduced. When extracellular macrolide was removed, intracellular macrolide concentrations became as low as 30% of the pre-wash concentrations in 5 min. KF lowered the transport ratios of josamycin and rokitamycin in particular and NaCN reduced the transport ratios of erythromycin and josamycin strikingly. Ouabain slightly lowered transport ratios of all the antibiotics tested except roxithromycin, and 2, 4-dinitrophenol decreased the transport ratio of clarithromycin markedly. The addition of various amino acids or hexose did not inhibit the transfer. Adenosine, however, inhibited the transfer of these antibiotics except erythromycin and lowered transport ratios by 83 to 92%. Puromycin reduced transport ratios of the same antibiotics by 59 to 95%. With polymorphonuclear leucocytes that had phagocytosed Legionella pneumophila serogroup 1, transport ratios of all five drugs tended to decrease. However, when Staphylococcus aureus ATCC 25923 or opsonized zymosan was phagocytosed, transport ratios for macrolides, except for roxithromycin, increased.
A 75 year old woman who was admitted to Higashisaga National Hospital due to chronic bronchitis showed a high fever (39.2 degrees C) and marked lymphadenopathy of the bilateral inguinal lymph-nodes. Chest X-ray showed diffuse infiltration. Cryptococcus was detected in biopsied lymph-nodes. Although 5-fluorocytosine, miconazole, amphotericin-B were administered for six weeks, she died and an autopsy was performed. Disseminated cryptococcosis was observed in the lung, liver, spleen, kidney, bone marrow, and lymph-nodes of the lung hilum, paratrachea, retroperitoneum, gall bladder and groin. She was a human T cell leukemia type I (HTLV-I) carrier, and this could be related to disseminated cryptococcosis.
Capsule-deficient Cryptococcus neoformans (CN-CD) infection is very rare. The authors recently experienced the case of CN-CD infection with the complication of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in a 83 year old woman. She was admitted to our hospital with the complaints of fever and general fatigue on June 10, 1987. At the time of admission, there were no abnormal findings except a mildly lowered consciousness level on physical examination, there were no abnormal neurological finding nor meningeal signs. Laboratory data revealed a mild leukocytosis and hyponatremia. Chest X-P showed a few small nodular shadows scattered in both lungs. Antibiotics therapy was of no help and hyponatremia became worse. Then with the suspicion of SIADH, Demeclocycline was administered and limitation of water intake was decreased and hyponatremia improvement was used. Yeast-like fungi was detected in the venous blood culture and in the cerebrospinal fluid (cell count: 252/3) CN-CD by India-ink preparation and bacteriological nature were determined. We made a diagnosis of sepsis and meningitis by CN-CD accompanied with SIADH. In spite of Miconazole administration intravenously and intrathecally, she died 2 months after admission. The minimal inhibitory concentration (micrograms/ml) of antibiotics against the isolated CN-CD was as follows: Amphotericin B: 0.78, 5-PC: 1.56, Miconazole less than or equal to 0.05, Nystatin: 25, Ketoconazole: 0.78.
Progress in chemotherapy and cardiosurgery has remarkably decreased the mortality due to infective endocarditis (IE) in recent years. In chemotherapy for IE, parental administration of antibiotics has been used routinely, the patients suffer from the psychological and physiological burden due to frequent injections and long period of therapy, even though the therapy for IE is successful. In this report, we present a case of IE caused by S. mitis, which was remarkably improved by oral administration of AMPC. A case, 69. y.o. female. She felt like a common cold and visited a G.P. Cardiomegaly was pointed out and positive inflammatory findings in serological examination were found. A low grade fever continued, and she was admitted to the hospital. Blood cultures were positive for S. mitis. For further examination, she was transferred to the university hospital. Based on the extensive blood cultures and cardioechogram, she was diagnosed IE caused by S. mitis. Because there were no symptoms of heart failure, we decided to try oral administration of AMPC, 4 g/day or 6 g/day at an interval of 6 hours. On the second day of therapy, the blood culture turned to be negative for pathogens, and on the fourth day body temperature became normal. On about the 60th day, the CRP finding became negative. Concentrations in the serum of AMPC were more than 10 folds of AMPC-MIC (0.5 microgram/ml) for S. mitis. The patient, however, suffer from complications of lung embolism and was operated for exchange of heart valves. After surgery, she has been well without any symptoms from IE.
Conventional chromogenic limulus test (toxicolor test) reacts with glucan of bakers yeast as well as endotoxin, because toxicolor test contains factor G which is sensitive to glucan and polysaccharide of fungus. A new endotoxin specific limulus test (endospecy test) was developed to improve reaction which responded only to endotoxin. The toxicolor test showed the positive reaction to the culture media of candida albicans 7N strain in RPMI 1640 medium, but the endospecy test did not. D-arabinitol, measured by fluometric enzymatic method, also was positive to culture media. These results suggested that a combination of the toxicolor and the endospecy test and enzymatic measurement of D-arabinitol could be applied to rapid diagnostic methods of fungal infection.
It has been recognized by clinical data that most of sepsis occurring in the immunocompromised host are endogenous infection. In recent years, we have investigated the mechanism of these bacteremia and sepsis by experimental studies using neutropenic mice treated with cyclophosphamide. And we evidenced that most pathogens causing bacteremia originated in the intestinal flora of the host. It has been shown that bacteria causing bacteremia were divided into two main groups, causing systemic bacteremia and causing portal bacteremia. Pseudomonas aeruginosa and Morganella morganii belonged to the former, on the other hand, Escherichia coli, Enterobacter cloacae and some other bacteria belonged to the latter. In this study, we studied the role of the reticuloendothelial system (RES) in the etiology of bacteremia or sepsis, using various kinds of bacteria isolated from bacteremic mice. As a result, the following facts were revealed. 1. It was suggested that the low blood clearance rate of the bacteria was one of the great risk factor of systemic bacteremia, since the blood clearance rate of bacteria causing systemic bacteremia was significantly lower than those of bacteria causing portal bacteremia. 2. Bacteria in the blood were eliminated by the RES, mainly by the liver, and the level of bacterial clearance by the liver was relative to the type of bacteremia which was systemic or portal. 3. It was suggested that the bacterial clearance by the liver mainly reflected the phagocytosis by Kupffer cells, and especially the adherence of these cells to bacteria as the first step of phagocytosis.
The effects of tricyclic antidepressant drugs on cardiac receptor binding sites and Ca2+ binding to cardiac sarcoplasmic reticulum were investigated in rats. 1) Quinupramine was found to possess higher affinity for muscarinic cholinergic receptor binding sites in brain and heart, compared with imipramine. 2) Repeated quinupramine treatment induced a significant increase in the Bmax value in cardiac muscarinic cholinergic receptors. 3) In imipramine treated heart, isoproterenol-induced stimulation of ornithine decarboxylase activity was significantly decreased compared with that in the vehicle control. 4) Repeated quinupramine and imipramine treatment caused a significant reduction of Bmax of 45Ca2+ binding in cardiac sarcoplasmic reticulum fractions. 5) After single quinupramine treatment, its concentrations in heart were higher than those in brain and plasma. 6) After the repeated quinupramine treatment, its concentration in heart was 2.4 times higher than that after single treatment. These results demonstrate that repeated tricyclic antidepressant drug treatment caused a functional impairment in Ca2+ binding sites of cardiac sarcoplasmic reticulum and adaptive changes of receptor binding sites.
Effects of 12 compounds including 5-lipoxygenase (5-LO) inhibitors and antiallergic drugs on the activity of 5-LO from the polymorphonuclear leukocytes (PMN) of guinea pigs, rats, rabbits, monkeys and humans were examined. The 5-LO activity was inhibited by the drugs according to the following orders of efficacy: Guinea pig 5-LO, 5-HDHDMF greater than TZI-2721 greater than NDGA greater than AA861 greater than FPL55712 greater than isoproterenol; rat 5-LO, 5-HDHDMF greater than AA861 greater than TZI-2721 greater than NDGA greater than FPL55712 greater than KP-136 greater than MCI-826 greater than benoxaprofen; and rabbit 5-LO, 5-HDHDMF greater than TZI-2721 greater than NDGA greater than AA861 greater than FPL55712 greater than KP-136 greater than MCI-826. The 5-LO activity from the rhesus monkey was dose-dependently inhibited by only 3 compounds, 5-HDHDMF greater than NDGA greater than TZI-2721, in this order, but the other compounds, except for AA861, did not show any effect on this activity. In humans, 5-LO activity was inhibited in the following order: TZI-2721 greater than 5-HDHDMF greater than NDGA greater than AA861 greater than FPL55712. From these results, it was strongly suggested that there is a species difference of this enzyme in its sensitivity to drugs.
Transthoracic needle aspiration of the lung in guinea pigs with experimental pseudomonas pneumonia was evaluated. The number of bacteria in aspirates correlated well with that of bacteria in the lungs which showed diffuse pneumonia (10(7) inoculum group). The number of deaths of experimental animals increased together with an increase of the times of aspiration. This procedure was also investigated in 16 patients of pneumonia and 17 patients of pulmonary abscess. The isolation rate of pathogen from pneumonia was 31.3% and that from pulmonary abscess 58.8%. A higher isolation rate was obtained with purulent aspirates. Predominantly anaerobic bacteria were isolated, and in pulmonary abscess usually in association with other bacteria. This method could be applied with success, for determining responsible pathogens. Even the normal oropharyngeal flora such as alpha-Streptococcus could be identified as pathogens. The complication rate was relatively low (6 out of 33 patients, 18.2%) including hemoptysis as a major one and pneumothorax or bloody sputum as minor ones. Transthoracic needle aspiration was reevaluated in experimental and clinical materials and was found to be an excellent and safe method for determining the responsible pathogen of respiratory infection.
To investigate the principle of Periotest measurement, we compared PT-value and the duration of contact between the rod of the Periotest-Instrument and the tooth measured directly in an oral cavity. Then we applied this apparatus to the subjects with normal periodontium and the patients of prosthetic treatment. The conclusions are as follows: 1. We confirmed that PT-value was calculated from the duration of contact between the rod of the Periotest and the tooth and it showed mainly the dumping effect of the periodontium. 2. There was a close relationship between PT-value and the clinical degree of tooth mobility, especially in the degree of 0 and 1 of tooth mobility. 3. Periotest was very useful not only for the periodontal treatment but also prosthetic application.
This study was executed at an opportunity for taking the impressions of a full crown abutment tooth by the five different methods with the four different impression materials; the copper ring tray on the abutment method with the polysulfide rubber, the resin ring tray on the abutment method with silicone rubber, the wash technique with silicone rubber, the hydrocolloid impression technique and the hydrocolloid-alginate impression technique. The reproducibility of the preparation margin on the ten stone dies was photographically measured and the following results were obtained. 1. The reproducibility of the preparation margin was affected considerably by the following conditions. 1) The character of the impression materials, 2) the position of the preparation margin in the gingiva sulcus and 3 the undercut degree beneath the preparation margin. 2. The impression technique with the individual ring tray on the abutment showed great utility under any condition of the preparation margin on the abutment. 3. The impression method should be selected clinically according to the condition of the abutment.
The effect of amlexanox on the non-immunological or immunological release of histamine or leukotrienes (LTs) from passively sensitized human lung fragments and atopic human leukocytes was investigated and compared with those of AA-861, tranilast, azelastine and disodium cromoglycate. 1) Amlexanox at concentrations of 10(-7)-10(-4) M showed an inhibition of histamine, LTB4, LTC4, LTD4 and LTE4 release from passively sensitized human lung fragments in a concentration-dependent fashion. A selective and competitive inhibitor of the 5-lipoxygenase activity, AA-861 modestly affected the histamine release and potently suppressed the any LT release at 10(-7) and 10(-6) M. Antiallergic drugs, tranilast and disodium cromoglycate also suppressed these chemical mediator release, but the inhibition potency was somewhat weaker than that of amlexanox. 2) Ca ionophore A23187-induced release of LTB4 and LTC4 from atopic human leukocytes was slightly enhanced up to 10(-6) M of amlexanox. However, 10(-4) M of the drug strongly diminished both of LT release. From these results, it is suggested that amlexanox is a clinically effective drug for atopic diseases, especially allergic asthma and rhinitis.
We had recently experienced two cases of tuberculous peritonitis. One was suspected of ovarian cancer but finally diagnosed as tuberculosis by the exploratory laparotomy. The other was found out casually at the operation of benign ovarian tumor. Both cases accompanied with pulmonary tuberculosis. Tuberculous peritonitis should be considered in the differential diagnosis in patients with abdominal disorders. Remarkable elevation of serum CA-125 related to ovarian cancer was found in both cases. It was suggested that level of serum CA-125 might be useful for diagnosis and monitoring of the disease.
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