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Severe renal toxicity due to intermediate-dose methotrexate.

Methotrexate (MTX) is a drug widely used in the treatment of patients with malignant disease. Its well-known side effects include myelosuppression, mucositis and renal damage. These problems are primarily dose-related, tending to occur more frequently when high doses (greater than 1 g/m2) are given. We present four cases in whom severe renal and mucosal toxicity occurred with intermediate doses (200 mg/m2) of MTX despite folinic acid rescue. Possible reasons for this occurrence are discussed and means of avoiding such toxicity are suggested. Three of four patients developed severe loin pain within a few hours of injection; the significance of this symptom in relation to subsequent renal toxicity has implications for early recognition of the problem.

Adult↗

An in vitro study on the cytotoxicity of chlorhexidine digluconate to human gingival cells.

Chlorhexidine digluconate is the active ingredient in mouthrinses used to prevent dental plaque and gingivitis. The in vitro cytotoxicity of chlorhexidine was evaluated with the Smulow-Glickman (S-G) gingival epithelial cell line. The potency of chlorhexidine was dependent on the length of exposure and composition of the exposure medium. The midpoint cytotoxicity values for 1-, 24-, and 72-h exposures were 0.106, 0.011, and 0.0045 mmol/L, respectively. S-G cells exposed for 2 h to chlorhexidine and then maintained for 48 h in chlorhexidine-free medium were unable to recover from the initial insult. The adverse effects of chlorhexidine on the plasma membrane were suggested by the leakage of lactic acid dehydrogenase from chlorhexidine-treated S-G cells and by the increased permeability of chlorhexidine-treated liposomes to Ca2+. The toxicity of a 24-h exposure to chlorhexidine to the S-G cells was progressively lessened as the content of fetal bovine serum (FBS) in the exposure medium was increased from 2% to 8%. The potency of a 1-h exposure to chlorhexidine was reduced in medium amended with albumin, lecithin, and heat-killed Escherichia coli. These reductions in toxicity were presumably due to the binding of the cationic chlorhexidine to the negatively charged chemical moieties of the components of FBS and of albumin and lecithin and of sites on the surfaces of bacteria. Combinations of chlorhexidine and carbamide peroxide were additive in their cytotoxicities.

Animals↗

The influence of a 0.2% chlorhexidine mouthrinse on plaque regrowth in orthodontic patients. A randomized prospective study. Part II: Bacteriological parameters.

In a prospective plaque regrowth study focusing on oral hygiene during fixed appliance therapy 12 adolescent patients (mean age 14.1 +/- 1.5 years) were evaluated twice over 2-day test periods. In the randomized, double-blind study the influences of a 0.2% chlorhexidine mouthrinse (Corsodyl, CHX) and a commercially available dentifrice supplementing fluoride (Odol-med-3) were compared intra- and interindividually in a crossover design with regard to the bacteriological parameters. The bacteriological parameters of vital fluorescence, bacteriological counts (BC), colony forming units (CFU), plating efficiency (PE) and mutans streptococci (MS) were related to the clinically assessed indices of plaque and gingivitis. All parameters analyzed demonstrated significant differences between the control and the test (chlorhexidine) group. Where-as the values of BC, CFU, and PE progressively increased in the control group from T0 to T2, these parameters distinctly decreased in the chlorhexidine group. All values of vital flora (VF) scored around 75% in the control group compared to values of 30% in the test group. BC, CFU und PE correlated significantly. The score of mutans streptococci persisted or increased in the controls whereas mutans streptococci approached 0 in the chlorhexidine group. Until the 5th day of washout a clear-cut carry over of the chlorhexidine rinse on mutans streptococci as well as on the gingival index was evident. Since dead microorganisms remain on the tooth surface and in order to maintain oral health, chlorhexidine application might advisedly be supplemented by mechanical plaque control.

Adolescent↗

The influence of a 0.2% chlorhexidine mouthrinse on plaque regrowth in orthodontic patients. A randomized prospective study. Part I: clinical parameters.

In a prospective plaque regrowth study focusing on oral hygiene during fixed appliance therapy 12 adolescent patients (mean age 14.1 +/- 1.5 years) were evaluated twice over 2-day test periods. In the randomized, double-blind study the influence of a 0.2% chlorhexidine (CHX) mouthrinse (Corsodyl) and a commercially available dentifrice supplementing fluoride (Odol-med-3) were compared intra- and interindividually in a crossover design with regard to plaque and gingivitis. Before starting the first test phase there was a 14-day preliminary phase for upgrading the oral hygiene. Between the 2 test phases was a 5-day "washout". On the last day of the second test phase the patients were asked to fill in a questionnaire concerning their experiences during the study. The 0.2% Corsodyl reduced the plaque index scores significantly (p < 0.001). The gingival index revealed a similar reduction (2nd day of test: p = 0.03). Until the 5th day of washout a clear-cut carryover effect of the chlorhexidine rinse on the gingival index was observed. Both the lower mean values of the 2 clinical parameters at the beginning of the test phases as compared with those at the beginning of the preliminary phase and the evaluation of the questionnaires indicated a possible Hawthorne effect. 0.2% Corsodyl may be employed as an adjunct to other preventive measures such as professional care and patient-oriented instruction on an intermittent basis in order to reduce the plaque-induced iatrogenic side effects and to enhance the efficacy of oral hygiene measures in connection with orthodontic therapy with fixed appliances.

Adolescent↗

Effects of EDITEMPA on dental calculus and caries formation in vivo.

N,N,N',N'-ethylene diamine tetra (methylene phosphonic acid)--EDITEMPA--was highly effective in reducing dental calculus formation in beagle dogs when applied topically as a 1% solution or in a mouth rinse. A dose-response study in 40 beagles for 12 weeks with dentifrices containing 1, 2, 2.75, and 2.75% EDITEMPA + 0.1% NaF gave a significant (alpha = 0.05) reduction in calculus formation. Based on these results, it was also concluded that 0.1% NaF did not affect the anticalculus activity of 2.75% EDITEMPA. The effect of EDITEMPA dentifrice on dental caries in rats was also studied. A dentifrice containing 1.69% EDITEMPA significantly (alpha less than 0.01) reduced smooth and fissure caries in rats when applied topically. Collectively, the data suggested that EDITEMPA was an effective anticalculus agent and that it did not damage developing enamel in vivo.

Animals↗

Lubrication of selected salivary molecules and artificial salivas.

The lubrication regime displayed by human salivas (parotid and submandibular-sublingual), purified salivary molecules (the mucins MG1 and MG2 and alpha-amylases), and selected artificial salivas (Oracare D, Saliva Substitute, and Orthana) was assessed in vitro using a friction-testing device. Thin-film (boundary) lubrication was observed for all of the salivary samples and two of the artificial salivas examined. Oracare D, a glycerol-based artificial saliva, was the exception since it lubricated by a thick-film (hydrodynamic) regime. On a molar basis, the best lubricants of the purified salivary molecules were MG1 greater than MG2 approximately nonglycosylated alpha-amylases approximately glycosylated alpha-amylases.

Amylases↗

Gargling with povidone-iodine reduces the transport of bacteria during oral intubation.

PURPOSE: Nosocomial pneumonia remains a common complication in patients undergoing endotracheal intubation. This study examined the transport of bacteria into the trachea during endotracheal intubation, and evaluated the effects of gargling with povidone-iodine on bacterial contamination of the tip of the intubation tube. METHODS: In the gargling group, patients gargled with 25 mL of povidone-iodine (2.5 mg.mL(-1)). In the control group, patients gargled with 25 mL of tap water. Before tracheal intubation, microorganisms were obtained from the posterior wall of the patient's pharynx using sterile cotton swabs. After anesthesia, all patients were extubated and bacteria contaminating the tip of the tracheal tube were sampled and cultured. RESULTS: Before orotracheal intubation, all 19 patients who gargled with tap water (control group) had bacterial colonization on the posterior walls of the pharynx. This group included five patients who had methicillin-resistant staphylococcus aureus (MRSA) in their nasal cavity preoperatively and MRSA was also detected in the pharynx of four patients. Bacterial colonization was observed in all 19 patients who gargled with povidone-iodine (gargling group) and four patients carried MRSA in their nasal cavity, although no MRSA was detected in the pharynx. In the control group, all the patients had bacterial colonization at the tip of the tube after extubation. Additionally, MRSA was detected in two of the four patients. In the gargling group, povidone-iodine eradicated general bacteria and MRSA colonies in the pharynx before intubation and at the tip of the tube after extubation. CONCLUSION: Gargling with povidone-iodine before oral intubation reduces the transport of bacteria into the trachea.

Anti-Infective Agents, Local↗

[Prevention of radiochemotherapy-induced mucositis. Value of the prophylactic mouth rinsing with PVP-iodine solution].

BACKGROUND: Oral mucositis is a frequent complication of radiochemotherapy. The origin of radiation-induced mucosa lesions is of iatrogenic nature although further development of mucositis is essentially influenced by infection. It can be assumed that disinfection measures should decrease the severity of mucositis induced by radiochemotherapy. Therefore, in a prospective randomised study the efficacy of prophylactic oral rinsing with a disinfection agent was investigated. PATIENTS AND METHOD: An open, randomised, prospective comparative trial was conducted with 40 patients undergoing radiochemotherapy of head and neck region due to malignant disease. The treatment scheme consisted of irradiation to tumor region and adjacent lymph nodes with a total dose of 71.3 Gy and simultaneous chemotherapy with carboplatin (60 mg/m2) on days 1 to 5 and 29 to 34. In all patients, a prophylaxis of mucositis with nystatine, rutosides, panthenol and immunoglobulin was undertaken. In addition, 20 patients rinsed oral cavity 4 times daily with povidone-iodine-solution, the comparative group rinsed with sterile water. Clinical examination of the oral mucosa was performed weekly. Onset, grading and duration of mucositis were used as main variables. RESULTS: Clinically manifested oral mucositis was observed in 14 patients of the iodine group (mean grading: 1.0) and all 20 patients of the control group (mean grading: 3.0). Total duration (mean) of clinically observed mucositis was 2.75 weeks in treatment patients and 9.25 in control patients. Median AUC (area under curve for grade vs duration) was 2.5 in iodine rinsing patients and 15.75 in control patients. All differences found between the 2 groups were statistically significant. Increased iodine incorporation was not observed. A pathological increase of thyroid hormone levels in the iodine group was not found. CONCLUSIONS: The gained results indicate that incidence, severity and duration of radiochemotherapy-induced mucositis can be significantly reduced by oral rinsing with povidone-iodine performed additionally to the standard prophylaxis scheme.

Adult↗

[Radiation-induced mucositis and neutrophil granulocytes in oral mucosa].

BACKGROUND: Chemotherapy-induced mucositis can be related to a decrease in oral neutrophils. We tested the relationship between radiation-induced mucositis and oral neutrophil counts. PATIENTS AND METHODS: Oral neutrophil counts were obtained for ten patients with head and neck cancer who received radiotherapy of the pharynx and oral cavity. Four patients received additional chemotherapy (5-FU, Mitomycin). Counts were obtained before and during treatment; four healthy volunteers were included in the study as well. For evaluation, a quantitative mouth rinse assay, including neutrophil-staining with acridin-orange, was applied. RESULTS: We observed large inter-individual variations with respect to neutrophil counts for patients and control persons (Table 1). During treatment (irradiation or chemoirradiation), large intra-individual variations were seen additionally (Figure 1). We found a correlation between neutrophil counts and clinical reaction grade. Neutrophil counts increased with increasing mucositis (Figure 2). This increase was more pronounced for patients treated with chemoirradiation compared to radiation alone. Treatment breaks at weekends had no clear influence on neutrophil counts. CONCLUSIONS: We observed a weak correlation between neutrophil counts and clinical reaction grade. However, the variations in neutrophil counts are too large to utilize this parameter as a surrogate for clinical mucositis grading. The assumption that a decrease in oral neutrophils is associated with radiation-induced mucositis was clearly negated.

Adult↗

Oral care reduces incidence of ventilator-associated pneumonia in ICU populations.

OBJECTIVE: To examine whether oral care contributes to preventing ventilator-associated pneumonia (VAP) in ICU patients. DESIGN: Nonrandomized trial with historical controls. SETTING: A medical-surgical ICU in a university hospital. PATIENTS: 1,666 mechanically ventilated patients admitted to the ICU. INTERVENTION: Oral care was provided to 1,252 patients who were admitted to the ICU during period between January 1997 and December 2002 (oral care group), while 414 patients who were admitted to the ICU during period between January 1995 and December 1996 and who did not receive oral care served as historical controls (non-oral care group). MEASUREMENTS AND RESULTS: Incidence of VAP(episodes of pneumonia per 1000 ventilator days) in the oral care group was significantly lower than that in the non-oral care group (3.9 vs 10.4). The relative risk of VAP in the oral care group compared to that in the non-oral care group was 0.37, with an attributable risk of -3.96%. Furthermore, length of stay in ICU before onset of VAP was greater in the oral care than in the non-oral care group (8.5+/-4.6 vs 6.3+/-7.5 days). However, no significant difference was observed in either duration of mechanical ventilation or length of stay between the groups (5.9+/-10.8 vs 6.0+/-8.8 days and 7.5+/-11.5 vs 7.2+/-9.5 days, respectively). Pseudomonoas aeruginosa was the most frequently detected bacteria in both groups. Number of potentially pathogenic bacteria in oral cavity was significantly reduced by single oral care procedure. CONCLUSION: Oral care decreased the incidence of VAP in ICU patients. DESCRIPTOR: Pulmonary nosocomial infection.

Chi-Square Distribution↗

Antimicrobial efficacy of antiseptic mouthrinse solutions.

OBJECTIVE: To assess the activity of different mouthrinse solutions compared to sterile water and sage tea against aerobe bacteria in the oral cavity. METHODS: The extent and the duration of the salivary bacterial count reduction were determined using a uniform model that allows a direct comparison of the different products. In contrast to previous investigations the antimicrobial activity of the tested products was stopped by specific neutralizers immediately after sampling. RESULTS: The obtained results allowed us to classify four categories of mouthrinse solutions according to their antimicrobial properties: Products without any active antimicrobial effect (sterile water, sage tea, Fluomint-Lysoform), products with a weak and temporary effect that does not exceed a salivary bacterial count reduction of 1.5 log of colony forming units (cfu) immediately and 1.0 log cfu 1 h after application (hydrogen peroxide, Meridol, Listerine, Lavasept), products with a strong immediate effect (> or =1.5 log cfu) but no prolonged activity (Betaisodona solution, acriflavine) and finally products that exert a sustained effect of at least 1.0 log cfu 1 h after application (Chloramine T, Gurfix, Skinsept mucosa, Corsodyl, Dobendan, Octenisept). CONCLUSION: The method used in this investigation allows an easy and reproducible evaluation of antimicrobial efficacy and may be part of a future test guideline for efficacy testing of antiseptics.

Adult↗

Topical polyene antifungals in hematopoietic cell transplant patients: tolerability and efficacy.

PURPOSE: The effectiveness of amphotericin B oral suspension versus nystatin oral suspension for the prevention of oral colonization by Candida in hematopoietic cell transplant (HCT) patients was examined. METHODS: Prior to hematopoietic cell infusion, 40 patients receiving systemic fluconazole for prophylaxis were randomized to receive either amphotericin B oral suspension or nystatin oral suspension, q.i.d. The study continued to day 21 or until the patient was discharge from the hospital or withdrawn from the study. Oral examinations were conducted twice weekly, and adverse events and compliance were recorded. Cultures were taken for quantitative counts and species identification. Candida isolates were assessed for resistance to the oral antifungal agents. Blood was collected for assessment of amphotericin B levels. RESULTS AND DISCUSSION: Ulcerative mucositis occurred in 84.6% of patients undergoing HCT, and no correlation was observed between the severity of mucositis and the presence of oral Candida and the severity of mucositis. Systemic and topical antifungal treatment resulted in a decrease in the number of colonized patients (54.8% before treatment; 23.1% during treatment); however, oral colonization was not eliminated. Tolerability of the oral rinse products was limited, with greater noncompliance in the amphotericin B than the nystatin group. Reports of altered taste appeared to be greater in the amphotericin B group. Minimal absorption of amphotericin B was seen following oral rinsing (serum levels 0.12-0.50 microg/ml), and no consistent changes in organism susceptibility to polyenes were seen. The results suggest that topical antifungal rinses may further control oropharyngeal colonization by Candida in patients on systemic antifungals receiving HCT, but the effect is limited by tolerability and reformulation and should be considered in order to increase compliance.

Administration, Oral↗

The role of basic oral care and good clinical practice principles in the management of oral mucositis.

BACKGROUND: The Basic Oral Care Group is one of eight subcommittees functioning within the Mucositis Study Group Guidelines Panel of the Multinational Association of Supportive Care in Cancer and International Society for Oral Oncology (MASCC/ISOO). The Basic Oral Care Group, comprised of the four authors of this paper, represented the disciplines of nursing (DBM, JJ), dentistry (MEPC), and pediatric dentistry (PW). This group reviewed research and clinical literature to update the original 2004 Mucositis Management Guidelines in the areas of basic oral care, bland rinses, protocols and education, and good clinical practices such as pain management, oral assessment, oral care, and dental care. MATERIALS AND METHODS: Over 100 articles published between 2000 and 2005 were identified, and 32 of these were useful for the analysis. Each article was rated by at least two authors using a structured rating form and systematic determination of levels of evidence, based on the American Society of Clinical Oncology criteria. Discussion at the 2005 MASCC/ISOO Geneva pre-conference meeting of the Guidelines Panel resulted in the development of consensus on the interpretation of the literature. RESULTS: Based on the literature and on Panel discussions, a revision of the original guidelines for protocols and education was produced by the group, and they developed a set of recommendations related to good clinical practices. CONCLUSIONS: Although research remains scanty for components of basic oral care, bland rinses, protocols, and education, the original 2004 guidelines with the help of newer literature from 2000 to 2005 and expert consensus among the Guidelines Panel enabled the development of useful clinical practice guidelines for managing oral mucositis in patients receiving cancer treatment with radiation and/or chemotherapy.

Benchmarking↗

Reduction of potential respiratory pathogens by oral hygienic treatment in patients undergoing endotracheal anesthesia.

PURPOSE: This study was conducted to evaluate the usefulness of mechanical and chemical prophylactic oral cleansing treatments for reducing potential respiratory pathogens existing in the oral cavity. METHODS: Thirty-two patients scheduled to undergo oral and maxillofacial surgery that required endotracheal anesthesia were randomly allocated to one of the two groups, the oral cleansing group (n = 16) or the noncleansing group (n = 16). Culture and polymerase chain reaction (PCR) methods were used to detect and enumerate pathogens. Oral cleansing was carried out with an electric toothbrush capable of automatically supplying and aspirating povidone-iodine solution before surgery, followed by rinsing twice a day after surgery. Cephazolin (3 g x day(-1)) was given to all patients for 5 days after surgery. RESULTS: The PCR detection rates of Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, and Porphyromonas gingivalis in gargle samples before treatment were 87.5%, 68.8%, 53.1%, and 40.6%, respectively. Oral cleansing reduced the detection rates and numbers of methicillin-sensitive Staphylococcus species, S. pneumoniae, and H. influenzae. In contrast, there was no significant reduction of methicillin-resistant Staphylococcus species, S. pneumoniae, H. influenzae, or P. aeruginosa in subjects who underwent systemic cephazolin administration without oral cleansing. CONCLUSION: The combination of mechanical and chemical oral cleansing resulted in a significant reduction of potential respiratory pathogens in the oral cavity.

Adult↗

Oral findings in patients with primary Sjögren's syndrome and oral lichen planus--a preliminary study on the effects of bovine colostrum-containing oral hygiene products.

Bovine colostrum is rich in antimicrobial substances and growth factors. The purpose of this open study was to examine and compare the interventory effects of daily use of bovine colostrum-containing oral hygiene products (CHP) on oral symptoms and findings in 20 patients with primary Sjogren's syndrome (pSS) and 20 age-matched patients with oral lichen planus (OLP). Objective oral measures and self-assessment of oral symptoms and general health were conducted before and after 90 days' use of CHP. The pSS patients had more systemic diseases, medication intake, oral dryness, poorer general health and lower salivary secretion than the OLP patients, who had the highest plaque index (PI) and the most mucosal soreness. Oral dryness and soreness were correlated to general health. In both patient groups. unstimulated whole saliva flow rate (UWS) had increased, PI and periodontal pocket depth (PPD) were reduced, and general health and oral dryness and soreness had improved after using CHP. A decrease in hyphae was found in candida smears from both groups and in blastospores in OLP smears. A reduction in the extension of the mucosal lesions was observed in 15 OLP patients. Results suggested beneficial effects of intervention with CHP on oral symptoms, general health, UWS, PI, PPD and candidal load in two patient groups--pSS and OLP--representing different oral symptomatology.

Adult↗