Age-related alterations in the auditory brainstem responses and the compound action potentials in guinea pigs.

The auditory brainstem response (ABR) and the eight nerve compound action potential (CAP) were measured using click click stimuli to investigate the age-related alteration in the auditory function in 66 guinea pigs consisting of four age groups. With advancing age, a gradual elevation of the thresholds in both the ABR and CAP was clearly seen, together with the prolonged latencies for waves I, II, III, and IV to clicks at 95 dBpeSPL in the ABR. There were some individual differences in either threshold elevation or latency prolongation of both the ABR and CAP in aged guinea pigs. These findings suggest that the effect of individual differences on degenerative aging processes of the auditory system should be considered in selected aged animals, although a significant elevation of the neural auditory threshold is clearly found with advancing age as a whole.

Interaction between oral alpha-streptococci and group A streptococci in patients with tonsillitis.

The incidence of oral alpha-streptococci with inhibitory activity against group A streptococci, as a defense mechanism against bacterial infection in the oral cavity, was investigated in 141 patients with streptococcal tonsillitis. The study population included both children (n = 79) and adults (n = 62). Infection by group A streptococci appeared to be more common in children than in adults, as the detection rates of inhibitory alpha-streptococci in healthy children (29.7%), as well as pediatric patients with tonsillitis (14.9%), were lower than those in adults (63.0%; p < .01). It is possible to consider oral alpha-streptococci with inhibitory activity to be among the indications for tonsillectomy in patients with streptococcal tonsillitis, since the detection rate of inhibitory alpha-streptococci in surgical cases (10.9%) was significantly lower than that in nonsurgical cases (31.1%; p < .01). The high detection rate of these strains during the postoperative state supported the observation that the incidence of group A streptococcal infection was decreased postoperatively. Accordingly, it is useful to investigate bacterial interference between oral alpha-streptococci and group A streptococci in patients scheduled for tonsillectomy.

Point, minute and small cancers of the stomach at the early developmental stage detected by improved chymotrypsin lavage method for diagnostic cytology.

The improved selective chymotrypsin lavage method under fluoroscopy for cytologic detection led to the discovery of 12 point or minute gastric cancer lesions of less than one cm maximum diameter among 420 patients. It is reported herein how tiny cancers of the stomach can be found by the method, and how valuable it is to employ morphologic criteria for correct identification of the individual atypical cells in these tiny gastric cancers.

Investigation of oral alpha-streptococcus showing inhibitory activity against pathogens in children with tonsillitis.

The incidence of oral alpha-streptococcus with inhibitory activity against group A streptococcus, as a defense mechanism against bacterial infection in the oral cavity, was investigated in pediatric individuals with tonsillitis. Infection by group A streptococcus appeared to be common in children, because the detection rate of inhibitory alpha-streptococcus in healthy children as well as pediatric patients with tonsillitis was lower than in adults and elderly patients. In particular, the detection rate of these strains was predominantly low in patients with beta-streptococcus. Among pediatric patients scheduled for tonsillectomy, the detection rate of inhibitory alpha-streptococcus was low preoperatively. However, the rate was markedly increased after surgery. The high postoperative detection rate of these strains reflected the decreased incidence of group A streptococcal infection. The results of this investigation of bacterial interference between oral alpha-streptococcus and group A streptococcus suggested that surgical treatment is a more effective approach for improving the oral bacterial flora in children with recurrent tonsillitis.

Effect of lactosucrose (4G-beta-D-galactosylsucrose) on fecal flora and fecal putrefactive products of cats.

The effects of lactosucrose (4G-beta-D-galactosylsucrose) on fecal flora and fecal putrefactive products were studied in 3 Himalayan and 5 Persian cats fed 175 mg of lactosucrose/each/day for 2 weeks. During lactosucrose administration, the counts of lactobacilli increased significantly (p < 0.05), whereas the counts of clostridia, including Clostridium perfringens and Enterobacteriaceace decreased significantly (p < 0.05). The levels of fusobacteria and staphylococci were decreased significantly (p < 0.01) on day 7 of lactosucrose administration, while the counts of bacteroides increased significantly (p < 0.05) and day 14 of lactosucrose administration compared to pre-administration. In frequency of occurrence, bifidobacteria increased significantly (p < 0.001) during lactosucrose administration, while Spirochaetaceae and lecithinase-negative clostridia decreased significantly (p < 0.05) on day 14 of lactosucrose administration compared to pre-administration. No detectable change occurred in the counts of other organisms throughout the experimental periods. Fecal concentrations of ammonia, indole, ethylphenol, and urinary ammonia were reduced significantly (p < 0.05) on day 14 of lactosucrose administration. The water content and weight of the feces increased slightly during lactosucrose administration, but the pH values decreased slightly. The environmental ammonia and the fecal odor also decreased remarkably (p < 0.01) during administration.

Effects of dietary supplementation with lactosucrose (4G-beta-D-galactosylsucrose) on cecal flora, cecal metabolites, and performance in broiler chickens.

The effects of dietary lactosucrose on cecal flora, cecal metabolites, and performance were studied in eight 20-d-old and eight 62-d-old broiler chickens fed a basal diet (control) or a diet with .15% lactosucrose added. On Day 20 of age, the frequency of occurrence of lecithinase-negative clostridia were decreased (P < .05) by lactosucrose consumption. On Day 62 of age, the numbers of bifidobacteria were increased (P < .05) by lactosucrose consumption, but the counts of lecithinase-positive clostridia, including Clostridium perfringens, bacteriodaceae, and staphylococci, total anaerobic bacteria, and the frequency of occurrence of pseudomonads were decreased (P < .05). No detectable change was observed in counts of other organisms throughout the experimental period. Cecal concentration of ammonia (P < .01), phenol (P < .05), and cresol (P < .05) were decreased on Day 62 of lactosucrose consumption. Acetic acid and butyric acid were increased (P < .01 and P < .05, respectively) on Day 62 of lactosucrose consumption. Environmental ammonia and odor of chicken ceca were greatly reduced by lactosucrose consumption.

[Growth inhibitory activity of clinical isolates of Pseudomonas aeruginosa against Staphylococcus aureus (MRSA and MSSA)].

Anti staphylococcal activity by clinical isolates of Pseudomonas aeruginosa was tested by the reversed agar plate and the filter paper stamp methods. Almost 40% of Pseudomonas aeruginosa inhibited the growth of both Methicillin resistant Staphylococcus aureus (MRSA) and Methicillin sensitive Staphylococcus aureus (MSSA). Green pigment (Pyocyanin) produced strains showed a strong inhibitory effect against MRSA and MSSA respectively. But some other pigment (Yellow, Red) strains also showed anti staphylococcal activity. These data suggest the colonization of Pseudomonas aeruginosa with anti staphylococcal activity may not be eradicated by the anti pseudomonic antibiotics.

[Clinical studies on septicemia and infective endocarditis encountered between 1985-1986].

Septicemia encountered at Kawasaki Municipal Hospital between 1985 and 1986 were studied clinically. Forty six patients had monomicrobial and 5 has polymicrobial infections, respectively. Out of these 46 patients with septicemia, 17 were due to Escherichia coli, 7 were due to Klebsiella pneumoniae and 4 were due to Staphylococcus aureus. Ten patients had hepatobiliary, 7 had hematological, 7 had malignant diseases as underlying diseases, respectively. Out of 10 patients complicated with septic shock, 7 died. Twenty three patients were community acquired infections. The age of most of the patients were over 50. The mortality rate of more than 65-year-old patients were higher than that of other patients. Our of 5 patients with septicemia due to polymicrobial infection, only 1 patient with erythroleukemia died. Fifty patients were treated mainly with beta-lactam antibiotics such as piperacillin or cefmetazole alone or in combination with aminoglycosides and so on. Three patients with infective endocarditis were encountered during this period. Two were due to alpha-streptococcus and 1 was due to Enterococcus. A 41-year-old patient with mitral valve insufficiency and metastatic gastric carcinoma to the bone marrow were complicated with disseminated intravascular coagulation. This patient, however, was successfully treated with a daily dose of 24 mega units of benzylpenicillin, and was given gabexate mesilate, concomitantly.

[Clinical studies on patients with legal communicable diseases encountered from 1981 to 1986].

Patients with legal communicable diseases admitted to Kawasaki Municipal Hospital between 1981 and 1986 were studied. Ages of patients were over 15 year-old. During this period 115 patients were admitted. Out of these patients 84 had Shigellosis, and 9 had amebiasis. Out of 20 Salmonellosis, 18 were due to Salmonella typhi and 2 were due to Salmonella paratyphi-A, respectively. Two were admitted because of Cholera. Out of the patients with Shigellosis, 27 were domestic and 57 were foreign infections, respectively. Most of patients were infected in South Asia or India and its neighbour countries. Shigella flexneri were mainly isolated from these patients. On the contrary, Shigella sonnei was the main causative organism of patients infected in Japan. Three amebiasis patients had liver abscesses with peritonitis, and 1 patient was a bisexual person. Out of Salmonellosis, 11 were patients with typhoid fever and 9 were carrier. One Cholera patient with severe diarrhea and acute renal failure was successfully treated and already reported elsewhere.

[Isolation of alpha-streptococci with inhibitory activity against pathogens, in the oral cavity and the effect of tobacco and gargling on oral flora].

We investigated the distribution of oral alpha-streptococci with inhibitory activity against pathogens, which compose an oral defense mechanism. Detection rate of alpha-streptococci with inhibitory activity against S. pyogenes and S. aureus derived from the tonsil was higher than in other portions, the tongue, cheek, gingiva, or saliva. It has suggested that tonsillar bacterial flora are mainly a defense mechanism. The oral flora in healthy smokers was compared with healthy non-smokers to investigate the influence of tobacco on oral bacterial flora. The results showed that the detection rate of S. aureus in smokers was higher while that of alpha-streptococci with inhibitory activity against S. aureus was lower. However, the detection rate of alpha-streptococci with inhibitory activity against S. pyogenes in smokers was as high as in non-smokers. It is suggested that it was easy for S. aureus to adhere to the oral mucosa in smokers, and was considered to influence the strain which produces beta-lactamase for medical treatment. We investigated the influence of gargling on oral bacterial flora by comparing the amount of bacteria before and after gargling with popidine-iodine gargle and saline solution. It was shown that alpha-streptococci, a main component of normal oral flora were decreased after gargling in both smokers and non-smokers. Furthermore, it was shown that group A Streptococcus was not decreased after gargling, and it was concluded that use of gargle medicinal mouth wash in bacillus carriers should be studied further.

[Effect of 14-member lactone ring macrolides on anti staphylococcal activity and swarming ability of Pseudomonas aeruginosa].

The purpose of this report is to examine the effect of Macrolides (Erythromycin and Roxythromycin) on swarming ability and antistaphylococcal activity of Pseudomonas aeruginosa. The standard strain (ATCC27854) and clinically isolated P. aeruginosa were used as test strains. The influence of Macrolides on antistaphylococcal activity and swarming ability were determined by the agar plate dilution method. The antistaphylococcal activity of P. aeruginosa was not affected at the concentration of 1.56 micrograms/ml of both Erythromycin and Roxythromycin. But the antistaphylococcal activity was not observed at the concentration over 100 micrograms/ml. The swarming ability was not affected at the concentration up to 12.5 micrograms/ml. It has been proved that Macrolides reveal inhibition of virulent factors of P. aeruginosa such as protease, elastase, piocianin and so on. Furthermore our data revealed that Macrolides inhibited swarming ability of P. aeruginosa, and did not affect the antistaphylococcal activity of P. aeruginosa under 1.56 micrograms/ml concentration. Consequently, these results suggest that Macrolides have exhibited a previously unknown pharmacological effect, and may be of interest in that there may be bacterial interaction between MRSA and P. aeruginosa.

[Participation in causing O.M.E. with nasopharyngeal alpha-Streptococcus].

The role of normal pharyngeal flora in the defense mechanism against infections in the upper respiratory tract was studied in 50 children with otitis media with effusion (O.M.E.). In the bacteriological study of the nasopharynx, the incidence of H. influenzae, S. pneumoniae, S. aureus, M. catarrhalis and group A Streptococcus was about 46%, 24%, 20%, 12% and 8%, respectively. The incidence of these species in the cases with O.M.E. was higher than that in the cases with chronic tonsilitis or control cases. In 41 O.M.E. cases with alpha-streptococci (82%), the incidence of alpha-streptococci with inhibitory activity against 5 pathogens (H. influenzae, S. pneumoniae, S. aureus, M. catarrhalis, group A Streptococcus) was examined. The detection rate of alpha-streptococcal strains with inhibitory activity against 5 pathogens derived from the nasopharynx in the cases with O.M.E. was significantly lower than that of the strain in the chronic tonsilitis cases and the control cases. Moreover, the detection rate of inhibitory alpha-streptococci from the nasopharynx was lower than that of from the tonsil. These findings suggest that the decline of inhibitory activity against pathogens by normal flora in nasopharynx is one of the factors causing O.M.E.

[Significance of normal oral flora, particularly group oral streptococci as defense mechanism against infection in healthy individuals (normal defense mechanism by oral Streptococcus group)].

The alpha-streptococci, consisted of normal oral flora mainly, with inhibitory activity against pathogenic microbes in healthy individuals was investigated by group A Streptococcus (indicator strain 6-22 nonmucoid T-12). Rate of alpha-streptococci with inhibitory activity against group A Streptococcus was increased as aging, and the rate in pre-school children was higher than that in school children. These results suggested that more than 90% of the tested alpha-streptococci with strong inhibitory activities (S. salivarius) against indicator strain had inhibitory activities against group A Streptococcus (mucoid T-6), H. influenzae, S. pneumoniae, group C Streptococcus, and from 40% to 70% of the tested strains had also inhibitory activities against other pathogens. As there were many strains of alpha-streptococci with inhibitory activities against pathogens, that usually detected in the upper respiratory infection, the problem on the strains in the future will explain significance of the defense mechanism against upper respiratory infection and this can be applied clinically.

[Effect of erythromycin on anti staphylococcal activity and dye production of Pseudomonas aeruginosa isolated from clinical materials].

Anti staphylococcal activity by Pseudomonas aeruginosa was investigated through the use of the reversed agar plate and the filter paper stamp methods. Investigation was also conducted on the dye production of different clinical isolates of Pseudomonas aeruginosa, the relationship between drug susceptibility and anti staphylococcal activity, and the influence of erythromycin on anti staphylococcal activity. Seventy four strains of Pseudomonas aeruginosa were prepared which included 20 strains from pus, 34 strains from sputum and 20 strains from urine. These were then inoculated with methicillin resistant Staphylococcus aureus (MRSA). They were then cultured for 48 hours by using the reversed agar plate and the filter paper stamp methods. Anti staphylococcal activity was observed in 16 strains from pus (80%), 19 strains from sputum (55.9%) and 8 strains from urine (40%). The Pseudomonas aeruginosa strains which have no pigment tended to show poor anti staphylococcal activity. Drug susceptibility was tested using PIPC, AMK, IPM, CFS and OFLX. The strains which showed resistance to OFLX tended to show poor anti staphylococcal activity. Erythromycin inhibited the dye production of Pseudomonas aeruginosa but exhibited no effect on anti staphylococcal activity. Consequently, these results suggest erythromycin has exhibited a previously unknown pharmacological effect, furthermore, anti staphylococcal activity was not caused by pigmentation only.

[Clinical study on SM-4300 in the field of internal medicine].

A new human gamma-globulin for intravenous use, SM-4300, was administered to 13 patients with infectious diseases. Five grams of SM-4300 was drip infused to each patient whose infection was not controlled by previous administered antibiotics. All of 13 patients had primary diseases besides infections. Thirteen patients were composed of 4 with pyelonephritis, 2 with pneumonia, 1 with bronchopneumonia, 1 with bronchitis, 1 with pyothorax, 2 with sepsis and 2 with cholecystitis. The results obtained were good in 3 cases, fair in 2 cases and poor in 7 cases. The results of a patient was not determined. No side effect was found including in laboratory findings.

[Clinical evaluation of clindamycin-2-phosphate in infectious diseases (author's transl)].

Clindamycin-2-phosphate (7(S)-chloro-7-deoxylincomycin-2-phosphate) is a new semi-synthetic antibiotic. It is recognized that the drug itself is inactive against bacteria in vitro but it is hydrolyzed rapidly to active clindamycin, drug intramuscular or intravenous administration. Clindamycin-2-phosphate was administrated intravenously to seven patients with infections, except one intramuscularly, 300 approximately 600 mg, every 8 or 12 hours a day, for 2 approximately 12 days. Three patients (1 bacterial pneumonia, 1 chronic bronchitis and 1 urinary tract infection due to E. coli) recovered from their infection; one patient (bacterial infection in bronchiectasis) partially responded; and three patients (1 urinary tract infection due to E. coli, 1 pneumonia due to Mycoplasma pneumoniae and 1 patient with mycoplasmal pneumonia and acute biliary tract infection) failed to respond to the drug. No remarkable side effect was noted except pain at intramuscular injection site in one patient.

[Clinical trial of fosfomycin for Campylobacter enteritis].

Forty-three children and 4 adults with Campylobacter enteritis were studied in the treatment of fosfomycin (FOM). FOM was administered per orally in doses ranging from 50 to 100 mg/kg/day for children and 3 g/day for adults for 5 days. Main symptoms such as diarrhea and fever were disappeared within 2 days on the average. Campylobacter jejuni in stool specimen disappeared within a week in 95% of these patients. The duration of main symptoms and the period of positive stool culture were evidently shortened in FOM-treated group compared with non-treated group. All of the isolated strains were sensitive to FOM by mono-concentration disk method. MIC50 of these strains remained between 1.56 and 3.13 micrograms/ml. None of these MIC was beyond 12.5 micrograms/ml.

[Incidence of alpha-streptococcus having inhibitory activity against beta-streptococcus in patients with tonsillitis].

Inhibitory activity against the proliferation of group A beta-streptococci by alpha-streptococci, part of the normal flora of the oral cavity and throat, plays a role in host defense against infection. We speculated that there might be some relationship between alteration of oral flora and the presence of recurring tonsillitis. Accordingly, 141 cases of tonsillitis have been investigated for the detection of inhibitory alpha-streptococci. In patients scheduled for tonsillectomy, the mean number of inhibitory alpha-streptococci was preoperatively decreased and postoperatively increased. In patients in whom beta-streptococcus had been detected (including patients scheduled for tonsillectomy), the mean number of inhibitory alpha-streptococci was markedly decreased, indicating a high incidence of beta-streptococci in patients with tonsillitis. As inhibitory strains of alpha-streptococcus are sensitive to almost all antibiotics, it is suggested that chemotherapy may disrupt the normal flora of the throat. In summary, investigation of the oral cavity and the throat for the detection of inhibitory alpha-streptococcus appear to be useful in the management of group A beta-streptococcal infection.

[Bacteriological investigation of the pre- and postoperative transition of the pharyngeal flora in the patients received tonsillectomy].

Several investigations have been reported on the interactive relation between the normal flora and the pathogenic micro-organisms in the human upper respiratory tracts (Thompson, Sanders, etc). It has also been known that some alpha-streptococci have inhibitory effect on the growth of group A beta-hemolytic streptococci. A study upon the role of alpha-streptococci in the throat (tonsil and pharynx) was performed using 73 culture specimens (throat swabs) obtained from 42 patients. Forty-four specimens were taken from the patients who received tonsillectomy, pre- and postoperatively, and 29 were from the patients who did not receive the operation. In the group of patients who received tonsillectomy, alpha-streptococci with inhibitory effect on the growth of group A beta-streptococci were detected less frequently preoperatively, when compared with the patients without tonsillectomy. On the other hand, postoperatively, marked increase of alpha-streptococci of these types was found in the normal flora of the throat. However, further detailed study on this subject is necessary because of the exceptional results in our observations.