We studied Enoxacin (ENX), a new-quinolon antibacterial agent, by comparing the drug concentration in tooth extraction wound blood with general concentration of the drug. The measurements were performed in 48 healthy volunteers 1, 2, 3, 4 and 6 hours after the drug was administered. The mean concentration in the tooth extraction wound blood and general concentration of ENX reached a peak after one hour. The drug concentration in the tooth extraction wound correlated well with the general blood concentration with a coefficient of correlation of 0.86. The drug was well accessed into the tooth extraction wound with a wound/blood concentration ratio of 1.323.

View full abstract

T-3262 (tosufloxacin tosilate), an oral antimicrobial agent of a new Quinolone derivative, was evaluated clinically in 229 cases with oral infections such as periodontitis, pericoronitis and osteitis of jaw. The daily dose of 150-600 mg was used, and the following results were obtained.
1) The clinical efficacy rate was 83.8% according to the numerical rating on the 3rd day of treatment, and 83.4% by the judgement of the doctor's in charge.
2) The highest clinical efficacy rate classified by diagnosis or severity was obtained dose of 150 mg t. i. d.
3) Side effects were obtained in four cases (1.7%) . However, the symptoms were not serious. Abnormal changes of laboratory findings were noted in three cases, but these were not serious.
4) A total of 282 strains were isolated from the pus of abscesses, of which 139 strains (49.3%) were anaerobes, indicating the important role of anaerobes in oral infections.
5) Streptococcus spp. were the major isolates, but Bacteroides spp., Peptostreptococcus spp., Fusobacterium spp, and anaerobic streptococci were also isolated with high frequency.

View full abstract

Bacteriological studies were carried out in the field of oral and maxillofacial surgery. Samples were gathered by means of needle aspiration from the closed abscess. Including 2 species fungi, the total number of isolated organisms was 285 species. Their susceptibilities to T-3262 (tosufloxacin tosilate), norfloxacine (NFLX), ofloxacin (OFLX) and enoxacin (ENX) were determined. The results were as follows.
1. The proportion of aerobes to anaerobes was 62.1% to 37.2% respectively.
2. The aerobes consisted predominantly of Oral Streptococci. The anaerobes consisted largely of Peptostreptococci and Bacteroides.
3. T-3262 demonstrated high effectiveness on the isolated organisms. NFLX and ENX had little effectiveness on the isolated organisms.

View full abstract

The distribution of T-3262 (tosufloxacin tosilate) was measured in New Zealand White rabbits after oral administration at a dose of 20 mg/kg.
T-3262 was detected in plasma, tongue, gingiva, submandibular gland, parotid gland, cervical lymph node and mandibular bone.
Pharmacokinetic parameters were caliculated from mean plasma levels and each tissue level by one compartment model and moment analysis.
The peak concentration of T-3262 was 4.54μg/ml in submandibular, 1.22μg/ml in parotid gland, 1.37μg/ml in cervical lymph node.

View full abstract

The clinical effectiveness, safety and usefulness of T-3262 (tosufloxacin tosilate), a new oral Quinolone antibacterial agent for the treatment of oral infections, was compared with that of Cefaclor (CCL) by a double-blind method.
The diseases covered by this study were periodontal infections, pericoronitis and osteitis of jaw. Drugs were administered for 3-7 days at doses of 150 mg t.i.d. (T-3262) and 250 mg t.i.d. (CCL) . A total of 259 cases were enrolled in the study.
Results obtained were as follows:
1) The clinical efficacy was evaluated by the doctors in charge and the numerical rating on the 3rd day of treatment in 246 cases (122 in the T-3262 group and 124 in the CCL group) .
The clinical efficacy rate according to the doctors in charge was 80.3% for the T-3262 group and 81.5% for the CCL group. The evaluation of the numerical rating was 86.9% for the T-3262 group and 85.5% for the CCL group.
There was no significant difference in clinical effectiveness between the two groups according to these two methods of clinical judgement.
2) Some side effects were observed in 3 cases (2.3% of 128) treated with T-3262 and in 5 cases (3.9% of 127) treated with CCL, but no severe symptoms were seen. Abnormal changes in laboratory findings were noted in 4.8% in the T-3262 group and 15.4% in the CCL group.
There was no significant difference in safety between the two groups.
3) In terms of clinical usefulness as well, there was no significant difference between the two groups.
From these results, it is concluded that T-3262 is as effective as CCL in the treatment of oral infections.

View full abstract

With patients who were to undergo tonsillectomy as subjects, a preoperative study was made of the flora and the composition of bacterial species on the surface tonsil and in the tonsil core. Bacterial content of blood immediately after the tonsillectomy was also examined. The results of the study were compared by dividing the subjects into the following three groups: non-treatment group, clindamycin phosphate (CLDM-P) group, and aminobenzyl penicillin (ABPC) group.
1) The species on the surface tonsil were all those that constitute oral flora. At the species level, aerobic bacteria and anaerobic bacteria were equal in number.
2) The number of bacteria on the surface tonsil was significantly less in the preventively administered CLDM-P group and ABPC group than in the non-treatment group.
3) The ratio of positive bacterial blood culture was 56.9% for the non-treatment group, 19.5% for the CLDM-P group, and 46.9% for the ABPC group. The reduction was significant in the CLDM-P group.
4) The distribution of CLDM and ABPC in the blood and the tonsil core differed greatly. The tonsil core level 2 hours after administration was 15.1μg/g for CLDM and 0.88μg/g for ABPC. These findings suggest that selection of drugs is also important in the preventive administration.
5) It was pointed out that problems relating to the preventive administration of antibiotics is one of the important issues confronting the modern medicine.

View full abstract

PT-01 is a controlled-release insert into the periodontal pocket. It consists of fast- and sustained-release parts containing ofloxacin. The ofloxacin level effective for periodontopathic microorganisms was maintained in the pocket for about 7 days afer insertion of PT-01. This study was designed to compare the clinical effectiveness and safety of inserting with and without PT-01. Eighty-three patients suffering from acute periodontal infections received crevicular irrigation and were assigned into PT-01 (T) and control (C) groups. PT-01 was inserted into some periodontal pockets of the affected teeth in T group at day 0. The average dose was 1.05±0.74 mg as ofloxacin. Clinical symptoms (spontaneous pain, tenderness, oppressive pain at chewing, gingival swelling, gingival flare, tooth mobility, bleeding on probing, pus discharge, and probing depth) were evaluated at day 0, 1, 3 and 7.
The following results were obtained:
1) All symptoms except for the tooth mobility were more significantly improved in T group than in C.
2) The clinical efficacy rate was 84.4% for the T group (45 cases) and 9.4% for the C group (32 cases) . The efficacy rate of T group was significantly (p<0.001) superior to that of C.
3) No side effects were observed in all 83 cases including 47 cases inserted PT-01.
From the above results, the topical chemotherapy using PT-01 could be effective for the treatment of acute periodontal infections.

View full abstract

We experienced a case of anaphylactic shock due to antibiotics (LMOX) .
1) A 56-year-old male was treated by intravenous antibiotic therapy for the infection secondary to MFH of the maxilla.
2) Intradermal test with LMOX before anaphylactic shock showed negative. We thought that it was a false-negative.
3) Patient suffered cardiac and respiratory arrest, but we succeeded in resuscitation with defibrillation and artificial ventilation.
4) Intradermal test and basophil degranulation test revealed that LMOX was positive one month after the anaphylaxis.
5) It was reconfirmed in our case that a through inquiry into the patient's history of allergy and Intradermal tests is needed to prevent anaphylactic shock.
If anaphylaxis occurs, prompt and proper treatment should be initiated.

View full abstract

CZX, 1 or 2g, was administered i.v. preoperatively to 16 patients operated on for maxillary sinusitis or with postoperative maxillary cyst, the serum, mucosa of the maxillary sinus and bone were obtained during operation, and the level of CZX in these tissues were measured. As a result, in the 1 g group (n=7) the mean serum level was 43.77 μg/ml, that in the maxillary sinus 16.2 μg/g and that in the bone 5.06 μg/g. In the 2 g group (n=9) the corresponding values were 55.24 μg/ml, 46.36 μg/g and 14.86 μg/g, respectively. The drug is considered to exist in concentrations higher than the MICs of many bacteria detected in diseases of the maxillary sinus.
Furthermore, this drug was administered to 31 cases to prevent postoperative infection and oral infection. Infections or aggravation of symptoms were found in no patients and results with an efficacy rate of 96.8% were obtained. Abnormal findings—a slight elevation of S-GOT and GPT—were found the only one patient. Thus, this drug is considered to be safe and highly useful in the field of oral surgery.

View full abstract

Gingival hyperplasia induced by Biphenyl hydantoin has been well docummented.
Recently reports have become available on gingival hyperplasia induced by the vasodilating drug Nifedipine, which is clinically and histologically similar to Piphenyl Hydantoin induced gingival hyperplasia.
We encountered a case of Nifedipine-induced gingival hyperplasia and performed gingivectomy after oral hygiene measures, this resulted in uneventful recovery, with no signs of recurrence.
The Nifedipine-induced gingival hyperplasia is rare and the mechanisms of action of Nifedipine are not clarified at present. But it is expected that the number of cases of Nifedipine-induced gingival hyperplasia may increase in Japan.
Thus we should consider the mode of chemotherapy and attempt to improve periodontal gingival treatment.

View full abstract

The study was conducted to examine the analgesic efficacy and safety of SR-318T, a sustained-release tablet containing dichlofenac sodium, after tooth extraction, 63 adult patients with postexodontic pain which needed an analgesic drug were each administrated with 2 tablets of (18.75 mg of dichlofenac sodium/1 tablet) .
1. The effective rate was 85.7% according to impressions of patients, and 82.5% in the judgement of the doctor.
2. Side effects reported in 3 of 63 patients (4.8%) ; such as warm feeling, drowsiness and heavy-headed feeling. However, these were slight symptoms and it was considered that there was no relationship with the administrating of SR-318T.
3. In the judgement by our group, the reduction of a pain was 50.8% and the speed was 88.9%, the duration of efficacy was 93.7% over “effective” respectively. The global effective rate was 85.7%. And the utility considering safety was 87.3%.
Concluding results of this study; it was considered that SR-318T is effective and safe for relieving postexdontic pain.

View full abstract

The purpose of this experiment was to investigate the tissue irritation induced by GP-Solvent, a newly designed solvent for removing the guttapercha point in the root canal. In this study, the degree of inflamatory response in the skin was observed after intradermal injection of “GP-Solvent” and other existing solvents into the dosal skin of guinea pig.
The results may be summarized as follows:
1. When Evans blue was used to evaluate the serum protein leakage, it was proved that the increased vascular permeability induced by “GP-Solvent” was comparatively weak, corresponding to 1/2 or less than that of chloroform and xylene.
2. “GP-Solvent” and chloroform were injected into the skin of guinea pigs, and after that, the tissue reactions were observed for 25 days.
With both solvents, an ulcer appeared on the injected site after 24 hours, but the one induced by “GP-Solvent” was undoubtedly mild compared to that produced by chloroform. Furthermore, the tissue injury produced by “GP-Solvent” was repaired in a shorter time than that induced by chloroform.
From the above results, it was concluded that the tissue irritation of “GP-Solvent” was significantly weaker than that of chloroform.

View full abstract

In the preceding paper, we reported that the inflammatory response of the local site induced by intradermal injection of “GP-Solvent” was significantly milder than that produced by chloroform.
In the present paper the inflammatory reaction induced by “GP-Solvent” on the oral mucosa of rabbits was compared with that induced by chloroform. The results were as follows:
1) The monitoring of serum protein leakage with Evans blue showed the increased vascular permeability in the oral mucosa when chloroform was applied topically on the mucosal surface for 5 minutes, while little effect appeared even after the application of “GP-Solvent” for 20 minutes.
2) The process of inflammation in oral mucosa was observed for 14 days after “GP-Solvent” and chloroform application for 5, 10, 20, 40 and 60 minutes respectively on the mucosal surface. With “GP-Solvent” contact even for 60 minutes, we did not find any changes on the application site during 14 days. However, chloroform contact for only 5 minutes caused the severe ulceration of the application site after only one day.
The above results proved that chloroform injured the oral mucosa seriously in contrast with “GP-Solvent.”

View full abstract

Branhamella catarrhalis is the pathogenic organism in respiratory infection.
Some investigators have suggested that this originates from normal flora of the oral cavity.
A survey on possible pathogenic bacterias and their susceptibilities to antibiotics in collaboration with many institutes of oral surgery was made over the period from 1982 to 1988.
Minimum inhibitory concentrations of the penicillins, cephems, macrolides and new quinolones against the Branhamella catarrhalis isolated from closed abscess of odontogenic infections were determined, and in some strains β-lactamase production was examined.
The following results were obtained.
1) Forty-nine strains of Branhamella catarrhalis were isolated from the closed abscess of 863 patients with odontogenic infections during the past seven years.
2) In 7 of 49 cases (14.3%) of Branhamella catarrhalis were isolated as a single infection and in 42 cases (85.7%) it was associated with other organisms.
3) β-Lactamase producing strains had resistance to ABPC and AMPC.
CTRX, OFLX, CPFX, Lomefloxacine and T-3262 had high effectiveness against β-lactamase producing strains.
Branhamella catarrhalis is a pathogenic organism different from non-pathogenic Nisseria, and β-lactamase producing Branhamella catarrhalis, it has resistance to β-lactams. The important thing in the choice of antibiotics is to make sure of the existence of β-lactamase production when Branhamella catarrhalis is isolated.

View full abstract

Two medicaments (formalin guaiacol: FG and formalin cresol: FC) have been investigated clinically as root canal antiseptics by ordinal criteria.
Three hundred and eighty-seven patients (pulpitis; 131 cases, periodontitis; 256 cases) participated in this study. Their endodontic treatments were carried out by routine endodontic technique, and clinical evaluation was completed at every visit according to several clinical symptoms which were shown on a protocol card (Table 2) .
The results can be summarized as follows:
1) FG and FC were effective for acute pulpitis and acute periodontitis. But in asymptomatic cases (234 cases), it was difficult to evaluate clinically the antiseptic effect on both medicaments.
2) No side effects in respect of FG and FC appeared in any of the cases.
3) It was suggested that there is a difficulty in evaluating the antiseptic effect of root canal treatment by clinical symptoms alone, therefore it is recommended to introduce some additional evaluation such as culture test.

View full abstract

We have made many reports about migration to tissues or organs of antimicrobial agents. The pharmacokinetic analysis of the experiments was performed by a program for personal computer made by the author. As the program is not standard, it is necessary to explain it.
In this paper, the structure and theory of the program is explained. And it is shown through several results calculated using that the program, is valid and useful.

View full abstract

Oral dose of 500 mg lenampicillin was administered before exodontia in 250 patients a sum total of 284 times.
Drug concentration as ampicillin in the blood from the exodontia wound was measured.
MIC 90% of the isolates from odontogenic infection including Oral Streptococci was 0.39μg/ml.
This antimicrobial agent valued≥0.39μg/ml 83 cases out of 88 cases (94%) between 60 minutes and 135 minutes after peroral administration.

View full abstract

The present study was undertaken to examine the alkaline and acid phosphatase (ALPase and ACPase) activities in the first lower molar tooth germs of rats cultivated under a lowcalcium environment. The right and left first lower molar tooth germs were extracted from 12 neo-natal Wistar strain rats. The right and left molar tooth germs were used as control and low Ca groups respectively. These tooth germs were cultivated in normal and low Ca culture media for 8 days, exchanging the culture medium every other day. ALPase and ACPase activities were measured on 0, 4 and 8 days in culture, using the Kind and King method (1954) . ALPase activity per pg protein was lower in the low Ca group than in the control group, and showed a tendency to decrease in the control group and to increase in the low Ca group time-dependently. The ratios of ALPase activity in the low Ca group to that in control group after 8 days in culture was higher than that after 4 days in culture. ACPase activity per μg protein showed a tendency to decrease in both groups time-dependently. ACPase activity was lower in the low Ca group than in the control group. The ratios of ACPase activity in the low Ca group after 8 days in culture was similar to that after 4 days in culture. From these results, it was suggested that ALPase activity showed a tendency to increase in the first lower molar tooth germs of rats cultivated under the low calcium environment.

View full abstract