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At least 19 recordsLinked to original sources

Pharmacokinetics and toxicity of tolonium chloride in sheep.

The pharmacokinetic disposition, urinary excretion and toxicity of tolonium chloride were determined after i.v. administration to sheep. Pretreatment with sodium nitrite significantly decreased the volume of the central compartment, apparent volume of distribution, area under the concentration-time curve, and total body clearance of tolonium chloride. Urinary excretion of tolonium chloride and its metabolite, leucotolonium chloride, together accounted for less than 15% of the administered dose in sheep receiving sodium nitrite and less than 10% of the administered dose in control sheep. The LD50 of tolonium chloride was 10 mg/kg with a 95% confidence interval of 7.35-13.60 mg/kg. Comparison with previously published data describing the pharmacokinetics and toxicity of a related compound, methylene blue, indicated that tolonium chloride has a higher volume of distribution and a narrower therapeutic index.

Animals↗

The utility of tolonium chloride rinse in the diagnosis of recurrent or second primary cancers in patients with prior upper aerodigestive tract cancer.

BACKGROUND: The clinical utility of tolonium chloride rinse was compared with unaided visual examination alone in the diagnosis of oral carcinoma in patients previously treated for carcinoma of the upper aerodigestive tract. METHODS: A total of 668 patients were enrolled in this multicenter study. At each site, an oral clinical visual examination was completed by one investigator followed by tolonium chloride rinse and examination by a second investigator blinded to the examination findings of the first investigator. If a lesion was considered suspicious (urgent biopsy required at the first visit), the lesion was biopsied after tolonium chloride rinsing. Patients with lesions characterized at the first visit as not suspicious (biopsy not urgent) or that stained with tolonium chloride were asked to return for a second visit. At the second visit, any residual lesion or lesions that retained tolonium chloride were biopsied. RESULTS: A total of 96 biopsies was performed in 81 of the 668 patients (12.1%), of which 30 (31.3%) were diagnosed histologically as carcinoma/carcinoma in situ (CIS) and the remainder as inflammation (31.3%), keratosis (26.6%), dysplasia (21.9%), ulcer (2.1%), other (3.1%), or no abnormality (1.0%). Of the 30 lesions with the diagnosis of carcinoma/CIS, 12 (sensitivity 40.0%) were considered to be clinically suspicious (CS+), whereas 29 (sensitivity 96.7%) retained tolonium chloride (p =.0002). The predictive values of a positive test for clinical examination and tolonium chloride staining were similar (36.4% vs 32.6%; p =.5871), indicating that the greater sensitivity of tolonium chloride was not associated with an excessive number of unnecessary biopsies (false positives). CONCLUSIONS: Tolonium chloride rinse is more sensitive than clinical examination alone in detecting lesions that might be found on biopsy to be carcinoma or CIS. The increased sensitivity is largely attributed to lesions that stain but were not detected clinically on visual examination.

Aged↗

Use of tolonium chloride in the diagnosis of malignant gastric ulcers.

Peroral staining with tolonium chloride (toluidine blue) was performed in 45 patients with suspected gastric ulcer disease. During endoscopy, 19 of 21 malignant ulcers and one of 15 benign ulcers were stained. Following surgery, 18 of 21 malignant ulcers found in the surgical specimens were stained. Eleven patients with benign ulcers underwent surgery and none of these ulcers were found to be stained in the surgical specimens. Normal gastric mucosa and areas of gastritis appeared unchanged. The data suggest that tolonium chloride staining prior to endoscopy or surgery seems to be helful in differentiating between minute benign and malignant gastric ulcers.

Adenocarcinoma↗

Photosensitizing effects of the tricyclic heteroaromatic cationic dyes pyronin Y and toluidine blue O (tolonium chloride).

Pyronin Y [3,6-bis(dimethylamino)xanthylium chloride; PY] and toluidine blue O [tolonium chloride; 3-amino-7-(dimethylamino)-2-methyl phenothiazin-5-ium chloride; TB] are cationic dyes commonly used in cytochemistry that have affinity to nucleic acids, predominantly to RNA. In live cells these dyes accumulate in mitochondria and sensitize the cells to light. The photosensitizing effects of PY and TB were compared with those of another mitochondrial cationic dye, rhodamine 123, and a noncationic dye, merocyanine 540, which binds to the cell membrane. Ninety % reduction of clonogenicity of human epidermoid carcinoma (A-253) cells pretreated with 3.3 microM PY, 0.67 microM TB, 13 microM rhodamine 123, or 18 microM merocyanine 540 was achieved by cell exposure to 0.7, 1.0, 1.2, or 1.5 J/cm2 doses of white light, respectively. The above concentrations of PY, TB, or merocyanine 540 represent the maximal ones at which the effect of each of these dyes alone, in the dark, in reducing cell clonogenicity was less than 12%. Exposure of A-253 cells to light at doses reducing clonogenicity by 50% caused a transient (24 h) arrest of the surviving cell population in the G1 phase of the cell cycle. In contrast to A-253 cells, Chinese hamster ovary cells were highly resistant to the photosensitizing effects of each of the four dyes. Also, the normal human lung fibroblasts (WI-38) were highly resistant to photosensitization by PY, whereas the simian virus 40-transformed WI-38 cells and another carcinoma line (OV-3) were sensitive. The data suggest that PY and TB, like other mitochondrial dyes, may have a selective antitumor photosensitizing activity.

Cell Cycle↗

Use of meta-analysis to evaluate tolonium chloride in oral cancer screening.

This study used meta-analysis, an analytical technique that uses raw data from previous researchers, to estimate the efficacy of screening for oral cancer with tolonium chloride (TCl). TCl, a vital blue dye, selectively stains acid tissue components such as DNA and RNA and has been used for more than 20 years by surgeons to identify suspected cancerous lesions. It has not been routinely used by dentists to screen either general or high-risk populations. Sensitivity and specificity, as well as positive and negative predictive values for the TCl test, were calculated. Sensitivity of TCl ranged from 97.8% to 93.5%, and specificity ranged from 92.9% to 73.3%. It was determined that if TCl is used to screen high-risk populations, the likelihood of a false negative finding is extremely low, whereas false positive results will be relatively numerous. However, given the high sensitivity of the test, the absolute number of false positive tests will be small. Further analysis is needed to evaluate the economic costs of false positives and false negatives, versus the value of identifying true positives at an early stage.

Cross-Sectional Studies↗

Antibacterial action of photoactivated disinfection {PAD} used on endodontic bacteria in planktonic suspension and in artificial and human root canals.

OBJECTIVES: To measure antibacterial action of photoactivated disinfection (PAD) on endodontic bacteria in planktonic suspension and root canals. METHODS: Four bacteria, Fusobacterium nucleatum,Peptostreptococcus micros, Prevotella intermedia and Streptococcus intermedius, were tested in suspension. After mixing equal volumes of Tolonium chloride and bacterial suspension for 60s, each 200 microL of concentration (>10(6)cfu mL(-1)) was irradiated with light at 633+/-2 nm. Each energy dose/Tolonium chloride concentration combination was tested eight times, with controls. Prepared root canals in Training Blocs and extracted human teeth were inoculated with S. intermedius followed by 10 mg L(-1) Tolonium chloride or saline. Bacteria in canals were sampled before and after light irradiation. Student t-test assessed significance of changes in viable bacteria produced by treatment of either light or Tolonium chloride alone and light/Tolonium chloride combinations. RESULTS: In suspension, reductions in bacteria were highly significant (P<0.01) for light/Tolonium chloride combinations compared to light or Tolonium chloride alone. Maximum mean log reductions of 1.14 (P. intermedia), 2.48 (P. micros), 2.81 (F. nucleatum) and 6.73 (S. intermedius) were at 4.8 J/20 mg L(-1). Antibacterial action was increased by energy dose increase (not always significantly), but not by Tolonium chloride concentration. In control canals mean log reductions of 0.42 (Blocs) and 0.38 (teeth) from initial levels were not significant. PAD mean log reductions of 2.40 (Blocs) and 2.01 (teeth) were highly significant. Changes for PAD/energy dose combinations were not significant. CONCLUSION: PAD killed endodontic bacteria at statistically significant levels compared to controls. Kills varied with bacterial species.

Anti-Bacterial Agents↗

Chemiluminescence as a diagnostic aid in the detection of oral cancer and potentially malignant epithelial lesions.

Chemiluminescence was evaluated as a diagnostic aid in the detection of oral cancer and potentially malignant epithelial lesions (PMELs) by comparing it against 1% tolonium chloride mouth rinse. Forty-six clinically identified lesions [14 primary squamous cell carcinoma (SCC), 26 PMELs and 6 benign lesions] and five cases of normal oral mucosa from 40 subjects (inclusive of 10 previously treated SCC cases) were examined with a commercial chemiluminescent kit (Vizilite) and tolonium chloride. Biopsy and histological verification of 31 lesions disclosed 14 SCC (45.2%), 10 epithelial dysplasias (32.3%), 5 lichen planus (16.1%) and 2 benign lesions (6.4%). For the remaining 15 lesions, a biopsy was not performed owing to patient's lack of consent or ill-health. The five cases of normal oral mucosa which tested negative for both tools were also not biopsied for ethical reasons. Sensitivity for Vizilite and tolonium chloride was 100% and 70.3%, respectively; and specificity was 14.2% for Vizilite and 25% for tolonium chloride. Their accuracy was 80.6% and 64.5%, respectively. Current findings suggest that chemiluminescence is a more reliable diagnostic tool than tolonium chloride in the detection of oral cancer and PMELs, and for follow-up of patients treated for the same.

Acetic Acid↗

Tolonium (toluidine blue) rinse--a screening method for recognition of squamous carcinoma. Continuing study of oral cancer IV.

Tolonium chloride (toluidine blue) application is useful for identifying malignant changes in squamous mucosa. However, early asymptomatic mucosal changes may remain undetected by tolonium application. A study was carried out to determine the feasibility of using a tolonium mouth rinse as a routine procedure after thorough clinical examination, to discover undetected cancers. A proved, effective tolonium application method was compared with a rinse sequence. One hundred five asymptomatic oral lesions (51 carcinomas and 54 nonmalignant lesions) that persisted for ten to 14 days were evaluated with application and rinse modalities and biopsies. There were 2% false-negatives (1/51) with the application as opposed to 5.9% (3/51) with the rinse and 9.3% false-positives (5/54) with the application as compared to 7.4% (4/54) with the rinse. Four inapparent, second primary cancers, unobserved for application, were delineated by the rinse (three oral, one pharyngeal). Tolonium blue rinse may be used to detect unobserved, asymptomatic oral mucosal cancers after clinical examination. After a positive rinse stain, a subsequent positive application stain ten to 14 days later mandates a biopsy of the lesion.

Carcinoma, Squamous Cell↗

Acute intoxication with aniline: detection of acetaminophen as aniline metabolite.

A 47-year-old woman unwittingly ingested an unknown substance together with her breakfast coffee. She suffered effects such as strong headache, generalized cyanosis, and a burning sensation of the lips and collapsed some minutes later. After admission into hospital a methemoglobin level of 35% was determined in the blood. Treatment by administration of tolonium chloride (toluidine blue) resulted in complete recovery of the patient. The toxic agent was identified as aniline by GC with mass selective detection after organic solvent extraction and 11 h after ingestion the plasma aniline level was 0.13 mg/l. Acetanilide (0.79 mg/ml) and acetaminophen (2.3 mg/ml) were identified in plasma as metabolites of aniline. It was assumed that a high metabolic capacity for acetylation protected the victim from more severe reactions. Her husband confessed later that he had tried to poison her.

Acetaminophen↗

Reliability of histologic diagnosis of clinically normal intraoral tissue adjacent to clinically suspicious lesions in former upper aerodigestive tract cancer patients.

Oral lesion biopsies often include adjacent clinically normal tissue to assess lesion spread, but the reliability of adjacent tissue histologic diagnoses has not been reported. Sixty-seven patients presenting with subsequent suspicious intraoral lesions underwent tissue staining with tolonium chloride. Biopsies of unstained tissue adjacent to suspicious lesions were reviewed by independent pathologists. The weighted kappa (kappa(w)) for histologic classification was 0.75 (95% confidence interval [CI] 0.64, 0.86) and was lower for: inflamed specimens [kappa(w)=-0.13 (95% CI -0.30, 0.05)] versus noninflamed specimens [kappa(w)=0.81 (95% CI 0.69, 0.92)], wedge biopsies [kappa(w)=0.58 (95% CI 0.37, 0.79)] versus punch biopsies [kappa(w)=0.90 (95% CI 0.83, 0.97)], and current smokers [w=0.59 (95% CI 0.32, 0.86)] versus past and never smokers [kappa(w)=0.82 (95% CI 0.72, 0.91)]. Histologic diagnosis of subsets of clinically normal oral specimens adjacent to suspicious tissue has low reliability. Molecular techniques may improve diagnoses in these subsets.

Adult↗

Intravenous injection of India ink with suicidal intent.

We describe the case of a 33-year-old man who injected 4 ml of India ink into one of the median cubital veins with suicidal intent. He was hospitalized in good general condition 10 h after the injection. Abnormal laboratory test results were a leukocytosis, an oximetrically determined methemoglobin level of 36.9% (normal range: 1.5%) and a free hemoglobin level of 74 mumol/L (normal range: < 25 mumol/L). Toxicological examination showed the presence of nitrobenzene in blood and urine. Intravenous administration of vitamin C and tolonium chloride plus forced diuresis led to an improvement in cyanosis and a fall in the methemoglobin concentration. Repeated increase in the concentration of aminobenzene were successfully treated by hemodialysis with a high-flux dialyzer.

Adult↗