Development and characterization of an animal model of dental sinusitis.

CONCLUSION: The results of this study confirm that the present rabbit model of dental maxillary sinusitis (dMxS) is reproducible and simulates human dental sinusitis with respect to initiation, progression and inflammation. It is applicable to further studies of sinusitis of odontogenic origin. OBJECTIVES: To induce acute dMxS in rabbits by using their own oral microflora to create a periapical infection and to follow morphological, radiographic, bacteriological and histological changes to the sinus mucosa. MATERIAL AND METHODS: The experimental animals comprised 26 New Zealand White rabbits. Maxillary premolar root canals were identified bilaterally and the continuously growing germs of the roots were severed by diathermy. The animals were randomized into 2 groups: in Group 1 (n=20) the teeth were left open for the entire study period; in Group 2 (n=6) the root canals were sealed 1 week after the initial intervention. The animals in Group 1 were sacrificed at intervals ranging from 2 h to 9 months after intervention. All animals in Group 2 were sacrificed 6 months after intervention. After macroscopic and radiographic examination, post-mortem inspection of the paranasal sinus cavity and maxillary complex and microbiological sampling, the entire nasal sinus complex with the hard palate in situ was resected and processed for serial coronal sectioning. RESULTS: In Group 1, after 3 months, the radiographic changes ranged from widening of the periodontal space to bone reaction. At sacrifice, changes in the sinus mucosa ranged from signs of mucosal inflammation to purulent dMxS. Microbial growth, predominantly Gram-negative aerobes, increased over time. In Group 2, the findings were generally more pronounced. Anaerobic microorganisms were predominant. In both groups the findings were consistent with dMxS.

Impact of antimicrobial agents on the gastrointestinal microflora and the risk of infections.

The most common and significant cause of disturbances in the normal gastrointestinal microflora is the administration of antimicrobial agents. The microflora can be influenced by antimicrobial agents because of incomplete absorption of any orally administered antimicrobial agent, secretion of an antimicrobial agent by the salivary glands and in the bile, or secretion from the intestinal mucosa. In most cases the influence is not beneficial to the patient because suppression of the indigenous microorganisms often permits potential pathogens to overgrow and cause septic conditions, diarrhea, or colitis. Antimicrobial agents that influence the normal microflora also promote the emergence of antimicrobial-resistant strains. The authors' experience on the impact of different beta-lactams, erythromycin, clindamycin, tetracycline, and nitroimidazoles on the gastrointestinal microflora and the risk of infections when these agents are used is reviewed.

Oral condition in children treated with bone marrow transplantation.

Oral health was studied in 49 children below 12 years of age treated with bone marrow transplantation (BMT). Dental treatment prior to BMT was required in 41% of the children. Ulceration of the mucous membranes in the mouth was observed in 37% of the patients during treatment. Those given methotrexate as prophylaxis against graft-versus-host disease (GVHD) exhibited oral ulcerations more frequently (p less than 0.05) than those given cyclosporin. One year after BMT all patients with a clinical chronic GVHD exhibited changes in the oral mucosa. During the first year after BMT 31% of the children developed carious lesions. Children treated with 10 Gy total body irradiation (TBI) had a significantly (p less than 0.05) reduced salivary secretion rate. Dental development was severely affected in children treated with TBI. These disturbances consisted of arrested root development, enamel hypoplasias and microdontia.

A randomized trial comparing use of cyclosporin and methotrexate for graft-versus-host disease prophylaxis in bone marrow transplant recipients with haematological malignancies.

Patients with haematological malignancies with HLA-identical marrow donors were randomized to treatment with cyclosporin (CSA) or methotrexate (MTX). Two of the 29 patients randomized to MTX died before engraftment compared with none of the 30 treated with CSA. Engraftment by leucocytes (P less than 0.0001), granulocytes (P less than 0.02), and reticulocytes (P less than 0.01) was faster among the CSA patients. There were no significant differences between the two groups regarding transfusions, hospitalization and incidence of early septicaemia. Granulocyte transfusions were required in seven of 29 MTX and two of 30 CSA patients (not significant: NS). Overall (grade I-IV) acute graft-versus-host disease (GVHD) was more common (P = 0.001) in the CSA patients. Grade II-IV acute GVHD was seen in 40% of the CSA patients compared with 22% in the MTX patients (NS). In the adult patients grade II-IV GVHD was slightly more common (P less than 0.05) in those treated with CSA compared with MTX. Chronic GVHD appeared in 30 and 39% in the two groups respectively. Actuarial 3-year survival was 58% for the CSA patients and 69% for the MTX patients. There were no significant differences regarding the incidence of interstitial pneumonitis or relapses between the two groups. The side-effects of CSA treatment includes nephrotoxicity (83%), hepatotoxicity (20%), hirsutism (43%), hypertension (23%), tremor (27%) and gingival hyperplasia (27%). Serum creatinine values were increased at 3 and 6 months in the CSA group but were within the normal range after 6 months. A blind study on oral side-effects revealed that CSA patients more often had a normal mucosa (P = 0.025) and less frequently had mucositis (P = 0.01) compared with the MTX group.

Reduced susceptibility to penicillin of viridans group streptococci in the oral cavity of patients with haematological disease.

The occurrence of oral penicillin-resistant viridans group streptococci (VGS) was studied in 50 patients with either newly diagnosed acute leukaemia or autologous peripheral stem cell transplants. One patient was excluded because of Staphylococcus aureus growth in the stem cell harvest. VGS were isolated from the oral cavity of 48 of the remaining 49 patients. Of these 48 patients, 12 (25%) yielded VGS resistant (MIC > 2 mg/L) to penicillin. These 12 patients had a higher frequency of septicaemia (p 0.04) and more days of treatment with trimethoprim-sulphamethoxazole (p 0.04) than patients who harboured susceptible or intermediately resistant VGS (MIC 2 mg/L). There were no other statistically significant differences between the two groups. It is important to be aware of the high level of penicillin resistance in oral VGS in patients with haematological disease, and this parameter should be considered when selecting antibiotic therapy for cases of septicaemia caused by VGS in immunocompromised patients.

Streptococcus mutans major adhesion surface protein, P1 (I/II), does not contribute to attachment to valvular vegetations or to the development of endocarditis in a rat model.

Streptococcus mutans P1 antigen functions as an adhesion factor for binding to salivary pellicle on tooth surfaces. It induces increased antibody titres in patients with Strep. mutans endocarditis. A mutant of Strep. mutans deficient in the function of the gene (spa P) encoding the surface antigen P1, and its isogenic parental strain, were used in a rat endocarditis experiment. Absence of P1 did not decrease adhesion to vegetations determined l h after intravenous infection. The number of bacteria recovered from valvular vegetations after 48 h from animals with manifest endocarditis did not differ between the strains. Consequently, the Pl antigen appears to be unimportant both for adhesion and virulence in endocarditis caused by Strep. mutans.

A comparative immunological analysis of the oral mucosa in chronic graft-versus-host disease and oral lichen planus.

Oral mucosal biopsies of 12 allogeneic marrow transplant recipients with chronic graft-versus-host disease (GVHD) involving the mouth were compared with biopsies taken before transplantation. They were also compared with biopsies from otherwise healthy patients with oral lichen planus, and with those from a control group of normal individuals. Biopsies from chronic GVHD exhibited a low number of infiltrating T lymphocytes (CD3 cells) compared with those from oral lichen planus, which showed intense cell infiltration (p less than 0.005). The ratio of CD4 to CD8 cells in biopsies taken after the manifestation of chronic GVHD exhibited no consistent variation compared with those taken before transplantation or with biopsies of oral lichen planus. The CD4/CD8 ratio in all groups investigated varied between 4:1 and 6:1. The number of natural killer cells (CD57), was increased in biopsy specimens taken before transplantation compared with the other groups. The frequency of homing receptor, Leu-8 bearing T cells was low in the biopsy specimens of all groups, compared with the corresponding frequency in peripheral blood (10-45 and 60-90%, respectively; p less than 0.001). In the biopsies from chronic GVHD and oral lichen planus the number of lymphocytes with transferrin receptors was increased compared with the pretransplant and control groups. Virtually no infiltrating cells were carrying interleukin-2 receptors (CD25) in any of the groups studied. Langerhans cells (CD1) were more frequently found in the specimens from chronic GVHD and oral lichen planus than in the pretransplant specimens and the control group (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

A micromethod for determination of antimicrobial agents in bone.

A microtechnique, requiring very small amounts of tissue material, was developed for assay of antimicrobial agents in bone. Without previous homogenization or extraction, small bone pieces (mean weight 0.014 g) from human subjects and pigs were placed into wells in agar plates preinoculated with the test strain. Round and distinct zones of inhibition were formed around the pieces. Standards for ampicillin and flucloxacillin were prepared from freeze-dried bone pieces from human subjects and pigs with known amounts of antibiotics as well as in human plasma and phosphate-buffered saline (PBS). Curves obtained from these standards were linear. Bone pieces from human and pig maxilla gave superimposable curves, but differed from curves obtained in plasma or PBS. The method was used in a pharmacokinetic study of bacampicillin in human maxillary bone and plasma. Bacampicillin tablets (2 X 400 mg) were given to patients before oral surgery. Standardized bone pieces and plasma samples were obtained at different times during surgery. The peak ampicillin concentrations estimated from the population curves were 8.0 mg/l in plasma and 1.1 mg/l in maxillary bone. The elimination half-life of ampicillin was similar in plasma and maxillary bone.

Pathological changes related to long-term impaction of third molars. A radiographic study.

Pathological changes related to impacted 3rd molars (ITM) were studied in a radiographic investigation of 2128 randomly selected patients. In radiographs from 644 patients, 1211 ITM were noted. Pathological changes were observed in 25 of 477 (5.2%) maxillary ITM and in 59 of 734 (8%) mandibular ITM. A pathologically widened pericoronal space (indicating a dentigerous cyst) was observed in 5 of 477 maxillary and 43 of 734 mandibular ITM (p less than 0.001). Other pathologic changes observed were resorption of the 2nd molars (1% in the maxilla, 1.5% in the mandible) or loss of marginal bone on the distal aspect of the second molars (4% in the maxilla, 1% in the mandible). The risk of pathological sequelae because of ITM, apparently, is low. Prophylactic surgical removal should, therefore, be regarded with some reserve, particularly in view of the high frequency of deep impactions, with greater risk for surgical complications.

Experimental mandibular Staphylococcus aureus osteomyelitis; antibody response and treatment with dicloxacillin.

Staphylococcus aureus mandibular osteomyelitis was produced in 20 rabbits by injection of a sclerosing agent and 1 X 10(9) colony-forming units of Staphylococcus aureus V8 into the medullary cavity of the mandible. After 2 weeks all rabbits developed infections. 10 of the rabbits were then treated with dicloxacillin (22.5 mg/kg body weight) every 12 h for 7 days and 10 were left untreated. The animals were sacrificed after 8 weeks and histopathological examination was performed. An enzyme-linked immunosorbent assay (ELISA) was used to measure IgG response against staphylococcal teichoic acid and alpha-toxin during the observation period. In the treated group, there was a decrease in clinical symptoms after the treatment period, while in the untreated group, progression of the infection was a common finding. At the end of the treatment period, Staphylococcus aureus V8 could not be recovered from aspirates obtained from animals in the treatment group, while in the non-treatment group, Staphylococcus aureus V8 could be recovered from abscesses in 6 rabbits. Both in the treated group and in the untreated group, the rabbits showed increasing IgG titers against teichoic acid and alpha-toxin during the first 2-3 weeks. No significant differences in antibody response patterns were noted between the treated and untreated groups and no clear correlation between the immunological response and the severity of the disease was observed.

Long-term results of amalgam versus glass ionomer cement as apical sealant after apicectomy.

A total of 67 teeth in 64 patients were treated with apicectomy and retrograde fillings. They were randomized to receive fillings of amalgam or glass ionomer cement in a comparative clinical study. Healing was evaluated clinically and radiographically after 1 and 5 years. Evaluation showed no difference in healing capacity between the two materials. Overall success rates in both groups were registered as 90% at 1 year and 85% at 5 years. Contamination with blood or saliva during insertion of the filling material did not affect healing adversely. The study shows that the 5-year follow-up result can be predicted in more than 95% of the cases at the 1-year follow-up. It can be concluded that glass ionomer cement is a valid alternative to amalgam as an apical sealant after apicectomy with equally good long-term clinical results.

Direct oral microscopy and its value in diagnosing mucosal lesions: a pilot study.

OBJECTIVE: Clinical examination of the oral mucosa often leads to an uncertain diagnosis, and a supplementary biopsy with a histopathologic examination of the lesion is necessary to establish a definite diagnosis. However, the site for the biopsy is a subjective choice that sometimes raises doubts about its representativeness. So far, no simple and reliable method is available for selecting the most appropriate area for biopsy. STUDY DESIGN: In a prospective study, we performed direct oral microscopy (oral application of the colposcopy technique used in gynecology) in 35 patients with various clinical diagnoses, such as leukoplakia, oral lichenoid lesions, or suspected malignancy. First, the oral mucosa was examined with direct microscopy, and the most representative site, according to colposcopic criteria, was selected. Then, the mucosa was clinically inspected by an independent examiner. The best site for biopsy according to clinical criteria was noted, and any difference in biopsy sites was recorded. Biopsy specimens were taken from 2 of these sites. RESULTS: Twenty-nine patients (83%) showed changes in the vascular picture on microscopy, according to the colposcopy criteria. In 14 patients (40%), the biopsy sites identified by direct oral microscopy showed more advanced histologic signs than those selected by routine clinical examination (0.01 < P

Dental implant installation without antibiotic prophylaxis.

The objective of this study was to retrospectively compare the outcomes of dental implant treatment with and without antibiotic prophylaxis. Two groups of patients with edentulous or partially edentulous maxillas or mandibles (or both) were treated with dental implants. One group, consisting of 147 patients (790 implants), was given prophylaxis with oral phenoxymethylpenicillin; 1 g of antibiotic was administered 1 hour preoperatively, and 1 g was administered every 8 hours for 10 days postoperatively. The other group, consisting of 132 patients (664 implants) was not given any antibiotics preoperatively or postoperatively. There were no significant differences with respect to early and late postoperative infections or with respect to implant survival between the two groups. It appears that antibiotic prophylaxis for routine dental implant surgery offers no advantage for the patient.

Antibody response in patients with osteomyelitis of the mandible.

Patients with mandibular osteomyelitis had quantification of 10 antibodies against certain bacterial proteins and polysaccharides. Sera from 31 patients with acute or chronic osteomyelitis of the mandible and from 17 healthy controls were analyzed. Some patients showed low levels of investigated antibodies in general and a lack of specific antiteichoic acid antibodies, as well as of different antipneumococcal antibodies particularly. Two patients with therapy-resistant osteomyelitis showed IgG2 and IgG3 subclass deficiency. They had replacement therapy with intravenous 10 or 15 gm immunoglobulin every 3 weeks for 6 months. Both patients showed considerable improvement in their clinical symptoms after treatment with immunoglobulin. This study indicates that impaired humoral immune response may be of importance in subgroups of patients with osteomyelitis of the mandible.

Bone grafting to the maxillary sinus from the lateral side of the mandible.

Patients who were unable to have an implant of the maxilla without a bone graft were operated on by a modified sinus lift method, under local anaesthesia. Cortical bone grafts, harvested from the lateral side of the mandible, were forced horizontally into a slot, made in the lateral sinus wall after a mucosal sinus lift. The immediate stabilization of the graft permitted the dense packing of the space below the horizontal graft with bone chips, which probably contributed to the fast healing of the bone. We saw eight patients (10 sites) for long-term follow-up. Two or three Brånemark standard implants were inserted into the grafted area 3 months postoperatively. The abutments were connected 5 to 6 months after implantation. We have now adopted this modified method as the standard for bone grafting to the maxillary sinus in both of our maxillofacial centres.

Selective suppression of the anaerobic oropharyngeal microflora with local metronidazole.

Anaerobic microorganisms of the normal oropharyngeal flora have been shown to be the main pathogens in orofacial infections of odontogenic origin. Reduction of the density of anaerobes in the oral cavity as a prophylactic measure before oral surgery may be a rational way to reduce the frequency of post-operative infections. This report describes a local antibiotic regimen that can reduce anaerobic pathogens in the oral cavity. Over a period of 7 days, 10 healthy individuals applied locally 1.5-2 g of an antibiotic preparation consisting of 0.5% metronidazole in 99.5% Orabase paste three times daily. The paste had antibacterial activity against obligate anaerobic micro-organisms such as bacteroides, fusobacteria and leptotrichia, known pathogens in orofacial infections. Fusobacteria and leptotrichia were eliminated in all subjects. Bacteroides species were eliminated in five subjects and significantly decreased in three subjects. The aerobic microflora was not affected. No new colonisation of the oropharynx was observed during the treatment period. The pre-treatment numbers of different micro-organisms were re-established within 2-9 days after the withdrawal of metronidazole treatment.

Oropharyngeal colonisation with fungi and gram-negative rods in patients treated with radiotherapy of the head and neck.

Twenty-five patients treated for malignant conditions of the head and neck were investigated for the development of oral radiation mucositis as well as oropharyngeal colonisation with fungi and Gram-negative bacilli. The colonisation rate of the patients increased from 20% to 80% during therapy. The patients were colonised mainly with fungi, but also to a lesser extent with Gram-negative bacilli. During radiotherapy free volatile fatty acids in saliva were determined by direct gas-liquid chromatography. The amounts of acetic, butyric and propionic acid decreased during radiotherapy and remained at low levels 6 months after therapy. Radiation induced mucositis was observed in 28% of the patients after 1 week of irradiation. After 3 weeks of therapy all patients showed varying grades of mucositis. In seven of the 19 survivors (36%) erythema was still present 6 months after radiotherapy.

Effect of chemotherapy on dental maturity in children with hematological malignancies.

Dental maturity or dental age was determined in 44 children with hematological malignancies treated with chemotherapy. No significant difference was observed between the chronological and dental age in children treated with chemotherapy compared to healthy controls. With regard to the number of erupted permanent teeth, no significant differences could be found between the two groups. The results indicate that chemotherapy given to children with hematological malignancies did not interfere with dental maturity or eruption of permanent teeth.

A double blind single dose comparison between two analgesics, rimazolium and acetylsalicylic acid in oral surgery outpatients.

The relief of pain after extraction of a mandibular third molar by two analgesics, rimazolium and acetylsalicylic acid (ASA) was studied in three groups of patients, who received either of these analgesics or a placebo. A questionnaire and careful instructions on its use were given to the patients. ASA had a better effect than both rimazolium and placebo. The results are discussed with regard to differences between analgesics with or without anti-inflammatory properties.

New trends in antibiotic prophylaxis of infective endocarditis in patients undergoing surgery in the oral cavity.

Viridans-streptococci, which normally reside in the oral cavity, are still the most common pathogens in infective endocarditis. During surgical procedures in the oral cavity, pharynx and respiratory tract, microorganisms may disseminate into the blood and cause infective endocarditis in predisposed patients. It is, therefore generally considered that these patients should be protected during surgery by an effective and simple antibiotic regimen. During recent years new recommendations for prevention of endocarditis have been presented in several countries. Single high dose amoxycillin or 2-dose phenoxymethylpenicillin are used in normal risk patients while 2-dose erythromycin or single high dose clindamycin may be used in patients allergic to penicillins. Parental agents are usually recommended in high risk patients with prosthetic heart valves, however, some countries prefer to administer peroral prophylaxis. Topical prophylaxis in the oral cavity is not included in any national recommendation, but may decrease the magnitude, as well as the frequency, of postsurgical bacteremia. Commonly used antiseptics such as chlorhexidine are not selective enough and causes overgrowth of some viridans-streptococci. More selectively acting agents, such as topical vancomycin, appear to be more suitable.