A randomized clinical study to assess ingestion of dentifrice by children.

This study investigated whether there was a difference in amounts of dentifrice ingested by children based on age using pea-sized instructions. The study had a randomized, single-blinded, 3-period, crossover design modelled after Barnhart et al. (1974) with one regular-flavored and two specially-flavored dentifrices used ad libitum. Subjects were enrolled in three groups: 2-4, 5-7, and 8-12 years. They were instructed to brush at home as they would normally with each dentifrice for 3 weeks (9 weeks total). On weekly study-site visits, subjects brushed with the assigned dentifrice containing a lithium marker to measure the amount of dentifrice ingested and used. Averaging across dentifrices, amounts ingested were: 0.205 g (2-4 yr), 0.125 g (5-7 yr) and 0.135 g (8-12 yr), demonstrating 2-4 year-olds ingested significantly more than older children (p ≤ 0.002). Averaging across dentifrices, amounts used were: 0.524 g (2-4 yr), 0.741 g (5-7 yr) and 0.978 g (8-12 yr) suggesting an age-related effect (p < 0.01). Findings also showed that ingestion amount for specially-flavored dentifrices may increase relative to regular-flavored dentifrice for children 2-7 years-old. This research demonstrated that dentifrice ingestion amount decreased significantly with age while usage amount increased with age. Importantly, ingestion and usage levels in younger children reflect "pea-sized" direction and were numerically lower than historical levels reported prior to this direction.

Placebo-controlled trial evaluating safety with 12-months continuous use of 6% hydrogen peroxide whitening strips.

OBJECTIVE: To assess the safety and tolerability of 6% hydrogen peroxide whitening strips over 12 months. METHODS: 80 adults were randomly assigned equally to one of two treatments: 6% hydrogen peroxide strips or placebo strips. Strips were worn 5 min daily for 12 months. Safety and tolerability were assessed via oral status interviews and oral examinations at baseline and after 1, 2, 3, 6, 9, and 12 months of use. RESULTS: Tooth sensitivity and oral irritation were the two most common adverse events. After 12 months use, tooth sensitivity was reported by 10% of subjects in the 6% strip group with a 95% confidence interval (CI) of (2.8%, 23.7%) and 5% of subjects in the placebo group with a 95% CI of (0.6%, 16.9%). The occurrence of reported oral irritation was 0% in the 6% strip group with a 95% CI of (0%, 8.8%) and 2.5% in the placebo strip group with a 95% CI of (0.1%, 13.2%). The occurrence of observed oral irritation was also similar between groups. The groups did not differ significantly (p>0.67) for the percent of subjects with each type of adverse event. In the 6% strip group, two subjects discontinued product use due to an adverse event (tooth sensitivity) compared to no subjects in the placebo group. Groups did not differ significantly (p>0.49) with respect to this outcome. CONCLUSION: Use of 6% hydrogen peroxide whitening strips over 12 months resulted in a safety profile similar to that seen with placebo strips.

An exposure-based risk assessment approach to confirm the safety of hydrogen peroxide for use in home tooth bleaching.

Hydrogen peroxide has a long history of safe use in a wide variety of medical and consumer products, including oral care products. The use of hydrogen peroxide in tooth bleaching has been extended to home use. Because this represents a new use, questions have been raised regarding safety, particularly the potential for peroxide tooth-whitening products to increase the risk of oral cancer in high-risk individuals (e.g., smokers and drinkers). These concerns are based on limited experimental data in animals that hydrogen peroxide has extremely weak tumor promoting activity and a lack of publicly available data on exposure to peroxides from the home use of tooth-whitening products. This paper provides a weight-of-evidence cancer hazard characterization for hydrogen peroxide and presents a quantitative risk assessment that confirms a favorable human safety profile risk associated with low levels of exposure to hydrogen peroxide from the use of tooth-whitening products. This includes a lack of tumor promotion risk which is important because tooth-whitening products are often used by chronic smokers and drinkers, who may represent a susceptible subpopulation because of their exposure to other known carcinogens.

Community-acquired bacterial meningitis in adults: categorization of causes and timing of death.

The relationship between cause and timing of death in 294 adults who had been hospitalized with community-acquired bacterial meningitis was investigated. For 74 patients with community-acquired bacterial meningitis who died during hospitalization, the underlying and immediate causes of death were identified according to the criteria of the World Health Organization and National Center for Health Statistics. Patients were classified into 3 groups: category I, in which meningitis was the underlying and immediate cause of death (59% of patients; median duration of survival, 5 days); category II, in which meningitis was the underlying but not immediate cause of death (18%; median duration of survival, 10 days); and category III, in which meningitis was neither the underlying nor immediate cause of death (23%; median duration of survival, 32 days). In a substantial proportion of adults hospitalized with community-acquired bacterial meningitis, meningitis was neither the immediate nor the underlying cause of death. A 14-day survival end point discriminated between deaths attributable to meningitis and those with another cause.

Vital tooth whitening with a novel hydrogen peroxide strip system: design, kinetics, and clinical response.

For many years, at-home whitening has been used with great success and produces some of the most satisfying results of all dental procedures. Historically, the most common procedure used was a custom-fabricated tray loaded with a 10% carbamide peroxide gel that was worn overnight. Today, many manufacturers offer higher concentrations (15% and 20% carbamide peroxide) for faster results. Regardless of the peroxide concentration used, the custom tray delivery system has remained essentially the same. Recently, a trayless whitening system was developed that does not require any prefabrication or gel loading. The new delivery system is a thin, conformable strip precoated with an adhesive hydrogen peroxide gel. Each preloaded strip is presented on a backing liner. To use the strip, it is peeled off of the backing liner and applied to the facial surfaces of the anterior teeth. Each strip is worn for 30 minutes, removed, and discarded. The strip holds the gel in place for sufficient time to allow the peroxide to intrinsically and extrinsically whiten the teeth. The highly flexible strips conform intimately to the tooth surface and provide a uniform, controlled application of the peroxide gel.

Time course of hepatic injury and recovery following coadministration of carbon tetrachloride and trichloroethylene in Fischer-344 rats.

Simultaneous administration of trichloroethylene (TCE), at an oral dose of 0.5 ml/kg, resulted in a marked potentiation of liver injury caused by an oral dose of carbon tetrachloride (CCl4, 0.05 ml/kg). Hepatic glutathione levels were depressed at 24 hr only in the rats given TCE and CCl4. Using serum enzyme (ALT and SDH) as indicators of hepatotoxicity, potentiation of CCl4-injury was most apparent at 24 hr. Upon histological examination of H&E stained liver sections, the differences between livers obtained from TCE and CCl4-treated rats versus CCl4-treated rats were most apparent at later time points (48 and 72 hr). At 48 hr after CCl4, livers showed a distinctive and uniform pattern of injury with regeneration features predominating over necrosis. At this time, livers from TCE and CCl4-treated rats were characterized by extensive zone 3 coagulative necrosis. Inflammatory infiltrations were less prominent. At 72 hr, morphological features of livers from TCE and CCl4 rats were similar to those from rats given CCl4 alone at 48 hr. From the results obtained, it appears that the regenerative activity of the liver may be delayed in rats simultaneously administered TCE and CCl4 as compared to rats administered only CCl4.

Pretreatment with drinking water solutions containing trichloroethylene or chloroform enhances the hepatotoxicity of carbon tetrachloride in Fischer 344 rats.

Previous studies have demonstrated that various compounds, including the common groundwater contaminants trichloroethylene (TCE) and chloroform (CHCl3), can produce a synergistic toxic response when coadministered with the model hepatotoxicant carbon tetrachloride (CCl4). This phenomenon has not, however, been demonstrated following administration of these compounds in drinking water. Initial experiments indicated that Fischer 344 (F-344) rats were significantly more sensitive to these effects than the more commonly utilized Sprague-Dawley strain. To establish the suitability of this strain as a model, a variety of indicators of hepatotoxicity was evaluated and compared to histological evidence of injury 24 hr after dosing with CCl4 or a combination of CCl4 + TCE. Plasma alanine aminotransferase (ALT) activity was the most reliable indicator of hepatic injury and was well-correlated with the histologic data. Dose-response studies utilizing simultaneous ip dosing confirm the sensitivity of the F-344 rat, demonstrating synergistic toxicity at doses as low as 0.165 mmol/kg of CCl4 and 0.6 mmol/kg of TCE. Synergism was also detected following simultaneous ip administration of 1 mmol/kg CCl4 and 0.5 mmol/kg of CHCl3. To evaluate the effects of drinking water exposure, rats were pretreated for 3 days with solutions containing TCE (0-40 mM) or CHCl3 (0-8 mM) stabilized with 1% Emulphor (EL-620P) as their only source of fluids. A single, ip dose of CCl4 (1 mmol/kg) was then administered and 24 hr later animals were killed for examination of liver histology and determination of ALT activity. Although none of the pretreatments were detectably hepatoxic, rats which drank 15 and 40 mM TCE or 8 mM CHCl3 exhibited an enhanced response to CCl4.

Polypharmacy in an Australian teaching hospital. Preliminary analysis of prevalence, types of drugs and associations.

A computer-based prescription retrieval system was used to study 21,521 prescriptions that had been provided to hospital patients who were receiving predominantly outpatient care. Over a three-month period 338 patients were found to be receiving 10 or more different drugs concomitantly. A further 338 patients were drawn at random from the same outpatient population for comparison. Age was linked significantly to polypharmacy (polypharmacy group: mean age, 63.7 years, SEM = 1.09; comparison group: mean age, 53.8 years, SEM = 1.00, P less than 0.05; chi 2 = 62.8, P less than 0.001). The relative risk of polypharmacy was related linearly to age. Admission to hospital was associated with increased prescribing rates in the polypharmacy sample (P less than 0.05), as was attendance at multiple clinics and multiple attendance at outpatient clinics (P less than 0.05 and P less than 0.05, respectively). Benzodiazepine agents were included in 63.7% of prescriptions in the polypharmacy group and in 37.3% of prescriptions in the comparison group. Non-prescription drugs were noted in 97.2% of prescriptions in the polypharmacy group and 58.0% of prescriptions in the comparison group, representing 34.7% and 27.3% of all items, respectively. In patients of less than 30 years of age agents for allergy/asthma/atopy contributed most to polypharmacy; agents that were associated with renal failure most in patients aged 31-50 years; and agents for cardiovascular disease contributed most in patients aged over 50 years. Our results suggest that a reduction in the use of non-prescription and psychotropic agents, heightened awareness of the dangers of polypharmacy and coordination and integration of over-all care and prescribing habits should reduce polypharmacy materially.

Amelioration of bromobenzene hepatotoxicity in the male rat by zinc.

Experiments were conducted to examine the role of zinc in the prevention of bromobenzene hepatoxicity in male rats. Bromobenzene (BB) (7.5 mmol/kg, ip) produced a marked hepatotoxicity as evidenced by increases in plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and a marked depression in hepatic glutathione (GSH) content 24 hr after administration. The administration of zinc (92 mumol Zn/kg, ip, at 48 and 24 hr prior to the bromobenzene) ameliorated the bromobenzene elevations in plasma AST (25%) and plasma ALT (50%) but did not alter the decreases in hepatic GSH. Following administration of [14C]BB, the radioactive label was distributed primarily in the cytosolic and lipid fractions derived from liver homogenates. Furthermore, the subcellular distribution of [14C]BB was not altered by zinc pretreatment. The extent of covalent binding of [14C]BB metabolites to hepatic tissue was significantly depressed in zinc-treated rats. Zinc induced the hepatic levels of metallothionein but [14C]BB did not bind to this sulfhydryl rich protein. Further experiments showed that zinc treatment depressed cytochrome P-450 content, the activity of NADPH cytochrome c reductase, and the metabolism of aniline, but not that of ethylmorphine. These studies suggest that the hepatoprotective effect of zinc against bromobenzene toxicity does not involve altered binding of the reactive toxic metabolite to glutathione or metallothionein, but it may be mediated by the inhibitory effect of zinc on the microsomal cytochrome P-450-dependent drug metabolizing system.

Factors influencing circadian rhythms in acetaminophen lethality.

Experiments were conducted to examine the effects of changes in lighting schedules and food consumption on circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice. Under a normal lighting schedule (light: 06.00-18.00 h), male mice exhibited a circadian rhythm in acetaminophen lethality (peak: 18.00 h; nadir: 06.00, 10.00 h) and an inverse rhythm in hepatic glutathione concentrations (peak: 06.00, 10.00 h; nadir: 18.00 h). Under a reversed lighting schedule (light: 18.00-06.00 h) the glutathione rhythm was reversed and the rhythm in acetaminophen lethality was altered showing greater sensitivity to the drug. Under continuous light, there was a shift in the acetaminophen lethality and the hepatic glutathione rhythms. Under continuous dark, both rhythms were abolished. Under a normal lighting regimen, hepatic glutathione levels were closely correlated with food consumption; i.e., both were increased during the dark phase and decreased during the light phase. Fasting the mice for 12 h abolished the rhythms in acetaminophen lethality and hepatic glutathione levels; moreover, the lethality was increased and the hepatic glutathione levels were decreased. These experiments show that both lighting schedules and feeding can alter the circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice.