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Oral complications of cancer therapies. Infectious and noninfectious systemic consequences.

Oral complications of cancer therapy often have systemic consequences. Pain and discomfort are common and can lower intake of fluid and nutrients, which in severe cases can lead to dehydration and malnutrition, requiring hospitalization. Oral infections are frequent accompaniments of cancer treatment. Herpes simplex virus is the most common symptomatic oral viral infection, and, in latently infected patients the virus is frequently reactivated after cytoreductive therapy. Viral (infectious) oral mucositis is often indistinguishable from noninfectious mucositis. Bacterial infections are less commonly observed today, perhaps because of the routine use of empiric broad-spectrum antibiotics; however, many episodes of septicemia in neutropenic patients apparently originate from oral microorganisms. Fungal infections are frequent and are usually due to Candida species. Spread to the esophagus or systemic dissemination can occur. Noninfectious oral mucositis can be used as a marker of toxic effects in other organs, especially hepatic veno-occlusive disease. In bone marrow transplant patients with mucositis, hepatic veno-occlusive disease is six times more frequent than in such patients without mucositis.

Bacterial Infections↗

[Antibiotic therapy of bacterial infections of the oral cavity].

More than 300 commencial bacterial species may be found in the oral cavity. Other microorganisms, such as mycoplasms, mycetes, protozoa and viruses are present as well. The virulency of the saprofites and additional contamination by outside microorganisms are factors determining the development of infectious process in the oral tissues. Moreover, streptococci and anaerobes are the most frequent aetiology agents. The antibiotic therapy should comply with the general treatment criteria, on the one hand, and should be specific for these microorganism, on the other. The penicillines (ampicillin, bacampicillin and especially amoxycillin) process pharmacokinetic properties which make them a favorable choice for treatment. These drugs are effective in case of streptococcal infections, with cariogenic processes involvement and dissemination (endocarditis, glomerulonephritis). Other, frequently used drugs are spiramycin, erythromycin, josamycin and myocamycin that are selectively taken up by the oral tissues and present in large quantities in the saliva. The macrolides have a large spectrum of action on microorganisms normally found in the oral cavity. Lincosamides (lincomycin and clindamycin) are active on anaerobes and are drugs of choice for treatment of staphylococcal osteomyelitis. Tetracycline therapy is restricted usually to parodontite cases caused by Actinobacillus actinomycetemcomitans and Capnocytophaga. In conclusion, the choice of antibacterial therapy should be based on the bacterial aetiology, as well as on the intrinsic drug characteristics (pharmacokinetic, side effects, toxicity etc.).

Anti-Bacterial Agents↗

Oral defense mechanisms are impaired early in HIV-1 infected patients.

We have examined the hypothesis that individuals infected with human immune deficiency virus type 1 (HIV-1) experience significant, specific alterations in mechanisms protecting the oral cavity prior to the appearance of AIDS-related systemic opportunistic infections. In a study of 13 early-stage, stable anti-HIV antibody positive patients, parotid salivary function was found to be generally intact. In contrast, several indicators of submandibular gland dysfunction were detected. In particular, stimulated fluid output was decreased and salivary lysozyme levels were increased relative to controls by 50-60% for both resting (p less than 0.05) and stimulated (p less than 0.001) conditions. Also, the frequency of albumin detection in submandibular saliva samples was approximately 65% in HIV-1 infected patients vs. 0% in controls (p less than 0.05). In addition, cytologic evaluation of oral mucosa revealed a fivefold increase in the prevalence of candidal hyphae in HIV-1 infected patients compared to controls (41% vs. 8%, p less than 0.05). We conclude that normal oral defense mechanisms show signs of compromise in HIV-1 infected individuals. We suggest that (a) effects of HIV-1 infection are seen early in the oral cavity, (b) impairment of oral defense mechanisms may facilitate entry of microorganisms with an attendant increased risk of morbidity and mortality, and (c) intensive oral surveillance and prophylactic care should be part of the routine management afforded to AIDS patients soon after HIV-1 infection is recognized.

Acquired Immunodeficiency Syndrome↗

The effect of bee propolis on oral pathogens and human gingival fibroblasts.

Propolis is one of the few natural remedies that have maintained its popularity over a long period of time. The aim of this study is to investigate the antimicrobial properties of six propolis solutions and evaluate their cytotoxicity on gingival fibroblasts at different dilutions. Two different solutions of powder propolis (Sigma) and Turkish propolis were prepared and propylene glycol (PG) and alcohol were used as solvents for each propolis sample. In addition to the four propolis solutions, two other propolis samples of far geographic regions (USA and Australia) were included in the study. The antibacterial effects of six solutions on oral pathogen microorganisms were tested and their cytotoxic effects on human gingival fibroblasts were evaluated by MTT assay. The effective dilutions of the six propolis samples on periodontopathogen microorganisms were found to be cytotoxic to gingival fibroblasts. All solutions had strong antifungal activity and the effective dilutions were safe for gingival fibroblasts. Propolis could have a promising role in the future medicine, if appropriate solutions can be prepared being strongly antibacterial and non-cytotoxic as well.

Adolescent↗

DNA probes in the diagnosis of periodontal microorganisms.

The need for a rapid and sensitive microbiological assay has become necessary for both research and clinical diagnostic purposes. This need has become clear as a result of extensive documentation linking specific bacterial species and periodontal destruction. DNA probe technology provides both a sensitive and specific assay and alleviates the concern for transport of fastidious microorganisms. The DNA probe procedure includes (1) disruption of bacterial cells with denaturation of DNA, (2) immobilization of DNA onto a nitrocellulose filter, (3) blocking unbound nitrocellulose with non-specific DNA, (4) hybridization of the filter with 32P-labelled probe, (5) washing and detection of bound probe. At our laboratory, microbiological analysis with whole-genomic and cloned DNA probes has been used on thousands of plaque specimens in several large-scale research projects. In one study, levels (greater than or equal to 10(5)) of Actinobacillus actinomycetemcomitans were significantly higher in subjects under 21 yr than in subjects with adult periodontitis (over 21 yr old). In another study, the distribution of periodontal pathogens throughout the mouth was examined. High levels were selectively found at sites with probing depths of 5 mm or more and bleeding on probing, directing specimen collection to these sites. In contrast, random selection of sites for sampling was found to be a poor method for detecting high levels of pathogens. These data suggest appropriate sites for specimen collection for further research and diagnostic purposes.

Actinobacillus↗

Systemic diseases caused by oral infection.

Recently, it has been recognized that oral infection, especially periodontitis, may affect the course and pathogenesis of a number of systemic diseases, such as cardiovascular disease, bacterial pneumonia, diabetes mellitus, and low birth weight. The purpose of this review is to evaluate the current status of oral infections, especially periodontitis, as a causal factor for systemic diseases. Three mechanisms or pathways linking oral infections to secondary systemic effects have been proposed: (i) metastatic spread of infection from the oral cavity as a result of transient bacteremia, (ii) metastatic injury from the effects of circulating oral microbial toxins, and (iii) metastatic inflammation caused by immunological injury induced by oral microorganisms. Periodontitis as a major oral infection may affect the host's susceptibility to systemic disease in three ways: by shared risk factors; subgingival biofilms acting as reservoirs of gram-negative bacteria; and the periodontium acting as a reservoir of inflammatory mediators. Proposed evidence and mechanisms of the above odontogenic systemic diseases are given.

Cardiovascular Diseases↗

[Effects of salivary ultrafiltrates on the production of phenol from tyrosine by oral microorganisms].

The metabolism of oral microorganisms is known to correlate with oral diseases. Protein degradation by oral microorganisms is usually followed by the production of phenol from tyrosine. The purpose of this study is to clarify the effect of salivary ultrafiltrates [MW: less than 10,000, 1,000-10,000 (intermediate fraction), less than 1,000, less than 500] on the production or the decomposition of phenol by oral microorganisms. Salivary sediment and salivary ultrafiltrate, the molecular weight of which is less than 10,000 unless otherwise stated, were incubated at 37 degrees C for 24 hours with tyrosine or phenol at a final concentration of 2.5 mg/100 ml. After incubation, the phenol produced (or remained) was extracted with ether and determined spectrophotometrically. Phenol production by oral microorganisms was not seen in the non-dialyzable fraction of saliva even when tyrosine was added. It was confirmed that the presence of the salivary ultrafiltrates was essential for the production of phenol by oral microorganisms. Phenol production in the salivary ultrafiltrate was further increased with the addition of tyrosine or non-dialyzable fraction of saliva. Phenol disappeared within 48 or 72 hours after the salivary sediment was incubated with phenol. The decomposition of phenol was inhibited with the salivary ultrafiltrate. Phenol production was enhanced with the addition of Good's buffer. Optimum pH of phenol production by oral microorganisms in the ultrafiltrate of saliva was within the range from 6.5 to 7.0 in the presence of Good's buffer (MOPS). Phenol production decreased with the reduction of the molecular weight of the salivary ultrafiltrates. The phenol production was increased when the intermediate fraction was added to the ultrafiltrate (MW: less than 1,000). The increase of the phenol production was considered to be due to the peptides in the intermediate fraction.

Bacteria↗

[Preflight Staphylococcus aureus carrier state of the cosmonauts].

A preflight study of Staphylococcus aureus carriage in cosmonauts has demonstrated that the microorganism harbors in 79.4% of the tested and microbial foci of the carriers amount to 10(2) ml. The isolated Staphylococcus aureus strains show a pronounced plasma coagulatory, alpha-toxic activity and 67.4% of them can be typed by the International set phages. Prophylactic administration of the native staphylococcal anatoxin increases specific antistaphylococcal immunity, reduces or eliminates completely Staphylococcus aureus in the upper respiratory airways.

Bacteriophage Typing↗

Metagenomics: the role of the microbiome in cardiovascular diseases.

PURPOSE OF REVIEW: The human oral and intestinal microbiota interact with the host through poorly understood metabolic pathways. Investigation of such complex ecosystems and interactions has been difficult. In this paper, we assess the current evidence supporting the role of the microbiota as a significant determinant of cardiovascular disease risk. RECENT FINDINGS: The link between oral disease and cardiovascular disease was established about 15 years ago. The accumulated evidence supports, but does not prove a causal association between periodontal infection and cardiovascular disease and suggests some physiologically obvious connections between these pathologies, namely, inflammatory and immune responses, and hemostasis. Moreover, some studies have observed higher concentrations of total and LDL-cholesterol and triglycerides and lower concentrations of HDL-cholesterol in individuals with periodontitis before periodontal treatment. Likewise, recent reports suggest the influence of the gut microbiome in the risk of common age-related diseases such as cancer and potentially cardiovascular disease through modification of classical risk factors such as obesity, insulin resistance and plasma lipids. SUMMARY: The recognition that microorganisms may play an even more important role in maintaining human health than in generating diseases places metagenomics as one of the most relevant areas of future research. The knowledge of the hundreds of genomes that we host and their interaction with our own genome shall provide a much more complete understanding of the individual nutritional needs and may be an obligated part of future personalized healthcare approaches.

Cardiovascular Diseases↗

Effect of nonsurgical periodontal therapy. III. Single versus repeated instrumentation.

Healing events following nonsurgical periodontal therapy were studied, comparing the effect of a single initial instrumentation to the effect of 3 instrumentations, each separated by 3 months. Incisors, cuspids and premolars with periodontal pockets up to 11 mm deep in 13 patients were treated by plaque control and supra- and subgingival debridement using ultrasonic instruments. A split mouth approach was used to compare the 2 frequencies of instrumentation. The results were evaluated by recording of plaque scores, bleeding on probing, probing pocket depths and probing attachment levels. A gradual and marked improvement of the periodontal conditions took place during the initial 9 months following start of therapy. During the remaining 15 months of the 24-month experimental period no further changes of the recorded parameters were noted. No differences in results could be observed when comparing the effects of a single versus repeated instrumentation. Thus, it appears that deep periodontal pockets in incisors, cuspids and premolars may be successfully treated by plaque control and 1 episode of instrumentation. The results also suggest that recurrence of disease due to subgingival recolonization by microorganisms during the healing phase may not be a major clinical problem.

Acute Disease↗

Type of fimbriation determines adherence of Klebsiella bacteria to human epithelial cells.

Clinical isolates of three Klebsiella strains (encapsulated and nonencapsulated mutants) with type 1 (mannose-sensitive, MS+MR-), type 3 (mannose-resistant, MS-MR+) and type 1 and 3 (MS+MR+) fimbriae were investigated for their ability to adhere to epithelial cells. Considerable adhesion to human buccal, tracheal, pulmonary and uroepithelial cells could be demonstrated. Independent of encapsulation and type of epithelial cells, adhesion of MS+MR+ (type 1.3) fimbriated Klebsiella bacteria was significantly stronger than adhesion of microorganisms carrying only type 1 (MS+MR-) or type 3 (MS-MR+) fimbriate, respectively. Adherence of nonencapsulated type 1 and 3 (MS+MR+) fimbriated Klebsiella bacteria to mammalian cells was significantly inhibited in the presence of D-mannose. Certain carbohydrates (D-glucose, D-galactose) did not interfere with this adhesion process.

Bacterial Adhesion↗

Resistance of the normal human microflora to mercury and antimicrobials after exposure to mercury from dental amalgam fillings.

The concentrations of mercury in saliva and feces and the resistance pattern of the gastrointestinal microflora were investigated for 20 subjects. Ten patients, with a mean number of 19 amalgam surfaces, had all amalgam fillings removed during one dental session. Ten subjects without amalgam fillings served as a control group. Saliva and fecal samples were collected before amalgam removal and 2, 7, 14, and 60 days afterward. Mercury levels in saliva and feces correlated significantly with the number of amalgam surfaces. No differences in the resistance pattern of the oral microflora were detected between the two groups. In the amalgam group there was an increase in the relative number of intestinal microorganisms resistant to mercury, ampicillin, cefoxitin, erythromycin, and clindamycin on days 7-14. This was not statistically significant in light of the normal variations of the control group. A significant correlation between the prevalence of mercury resistance and multiple antimicrobial resistance in intestinal bacterial strains was observed.

Adolescent↗

Selective decontamination of alimentary tract microbial flora in patients treated with bone marrow transplantation. A microbiological study.

14 patients undergoing bone marrow transplantation were studied regarding the oral and faecal microflora. Seven patients were given a multidrug regimen, directed against aerobic gram-negative rods and fungi, for local decontamination of the oral cavity and gastrointestinal tract. Seven other patients served as controls. The decontamination regimen was found to decrease the numbers of fungi in the oral cavity and to protect from new colonization. In the gastrointestinal tract aerobic gram-negative rods were eliminated in all patients and new colonization with acquired microorganisms was not observed even when the indigenous anaerobic flora had been disturbed by parenteral antibiotics. In the control group aerobic gram-negative rods and fungi were isolated from all patients during the observation period.

Adolescent↗

[Antioxidant profile of human saliva and its biological significance].

Saliva is the first biological medium to come in contact with materials entering the body through the oral cavity. These materials are contained in food and drink (or inhaled as volatile ingredients). Accordingly, saliva contains various defense mechanisms which have been thoroughly investigated. They include immunological and enzymatic systems aimed at pathological microorganisms. Saliva also can protect the mucosa against mechanical insults and when required, promote its healing via agents such as the epidermal growth factor. Another defense mechanism in saliva which has been gaining increased attention and seems to be of paramount importance is its antioxidant system. We discuss both the molecular and enzymatic components of the salivary antioxidant system in respect to mixed, parotid, submandibular and sublingual saliva and under various physiological conditions of secretion.

Antioxidants↗

[Microflora of the posterior pharyngeal wall, larynx and postoperative wounds in patients after laryngectomy].

The study group were persons with risk factors of colonization by pathogenic strains and included smokers, patients suffering from paradontosis, and patients with visibly neglected oral cavity and teeth. We isolated and classified to the species or genera 488 microorganisms. Of posterior pharyngeal wall flora, 61% of were Gram-negative bacteria, represented predominantly by Haemophilus and anaerobic rods and aerobic cocci belonging to the Neisseria and Moraxella (Branhamella) genera. In the group of Gram-positive cocci (34% of the total number of microorganisms), oral streptococci, Stomatococcus mucilaginosus and Streptococcus pneumoniae were isolated most frequently. The affected by neoplastic lesions larynx, was colonized by similar bacterial groups. However, the incidence of Gram-positive cocci was higher. The main etiologic factor of purulent post-operative wound inflammations were methicillin-resistant Staphylococcus aureus strains (MRSA), which had been absent among the bacteria isolated from patients on admission.

Gram-Negative Bacteria↗

The effects of cadmium on the growth of some oral microorganisms and their ability to bind cadmium.

All seven oral Actinomycetaceae tested grew in broth containing 10 microgram/ml Cd. After 24 hours' growth A viscosus WVU 626 bound nearly 20 microgram Cd/mg dry wt. The amount of Cd bound varied during the growth cycle, being maximal (90 to 100 microgram/mg dry wt.) after 5 hours' growth. Addition of 50 microgram/ml chloramphenicol to actively growing cells inhibited further Cd binding. In contrast S mutans FA1 was greatly inhibited by 2.5 microgram/ml Cd and bound only 1.3 microgram Cd/mg after 24 hours' growth in broth containing 2.5 microgram/ml Cd.

Actinomyces↗

Bloodgroup simulating activity in aerobic gram-negative oral bacteria cultured from fresh corpses.

The gram-negative aerobic oral bacterial flora of 100 consecutive corpses was isolated. After the identification and culturing of the isolated organisms, blood grouping was performed by the haemagglutination inhibition technique on dried culture smears, the dried culture medium and a dried ethanol extract of the bacteria. Forty-seven of the samples showed a gram-negative aerobic bacterial growth, giving 58 microorganisms of 14 different species. Positive blood grouping results were found in two of them (Escherichia coli and Serratia marcescens), both of type B. It is concluded that occasional mistyping of blood groups on saliva and oral material may be caused by the oral gram-negative aerobic flora, especially if the specimens are contaminated or putrefying.

Blood Grouping and Crossmatching↗

Selective antimicrobial modulation of human microbial flora: infection prevention in patients with decreased host defense mechanisms by selective elimination of potentially pathogenic bacteria.

To reduce the frequency and severity of bacterial infection, selective antimicrobial modulation (SAM) was applied in 39 patients with severely decreased host defense mechanisms. The objective was to eliminate potentially pathogenic aerobic microorganisms with minimal disturbance of the normal anaerobic bacterial flora. Elimination of potentially pathogenic aerobic microorganisms was easily accomplished in patients not infected at hospitalization. The anaerobic flora seemed to be undisturbed, and selection of or overgrowth with resistant microorganisms did not occur. The microbiologic results of the SAM regimen correlated with the incidence of infection. Only three major infections occurred in 23 patients who were free of potentially pathogenic microorganisms; 10 major infections occurred in 16 patients who were not free of potential pathogens. Seven of these 10 infections were present at hospitalization. The incidence of major infections was 47% in the patients on the SAM regimen and 82% in a group of control patients with a similar risk of infection.

Adolescent↗