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Purpose: Active surveillance (AS) is an option for the initial management of early-stage prostate cancer. Current risk stratification schema identify patients with low-risk disease who are presumed to be most suitable for AS. However, some men with higher risk disease also elect AS; outcomes for such men have not been widely reported., Patients and Methods: Men managed with AS at University of California, San Francisco, were classified as low- or intermediate-risk based on serum prostate-specific antigen (PSA), Gleason grade, extent of biopsy involvement, and T stage. Clinical and demographic characteristics, and progression in terms of Gleason score, PSA kinetics, and active treatment were compared between men with low- and intermediate-risk tumors., Results: Compared to men with low-risk tumors, those with intermediate-risk tumors were older (mean, 64.9 v 62.3 years) with higher mean PSA values (10.9 v 5.1 ng/mL), and more tumor involvement (mean, 20.4% v 15.3% positive biopsy cores; all P < .01). Within 4 years of the first positive biopsy, the clinical risk group did not differ in terms of the proportions experiencing progression-free survival, (low [54%] v intermediate [61%]; log-rank P = .22) or the proportions who underwent active treatment (low [30%] v intermediate [35%]; log-rank P = .88). Among men undergoing surgery, none were node positive and none had biochemical recurrence within 3 years., Conclusion: Selected men with intermediate-risk features be appropriate candidates for AS, and are not necessarily more likely to progress. AS for these men may provide an opportunity to further reduce overtreatment of disease that is unlikely to progress to advanced cancer.

Background: How case volume and quality of care relate to hospital costs or length of stay (LOS) are important questions as we seek to improve the value of health care., Methods: We conducted an observational study of patients 18 years or older who underwent coronary artery bypass grafting surgery in a network of US hospitals. Case volumes were estimated using our data set. Quality was assessed by whether recommended medications and services were not received in ideal patients, as well as the overall number of measures missed. We used multivariable hierarchical models to estimate the effects of case volume and quality on hospital cost and LOS., Results: The majority of hospitals (51%) and physicians (78%) were lowest-volume providers, and only 18% of patients received all quality of care measures. Median LOS was 7 days (interquartile range [IQR], 6-11 days), and median costs were $25 140 (IQR, $19 677-$33 121). In analyses adjusted for patient and site characteristics, lowest-volume hospitals had 19.8% higher costs (95% CI, 3.9%-38.0% higher); adjusting for care quality did not eliminate differences in costs. Low surgeon volume was also associated with higher costs, though less strongly (3.1% higher costs [95% CI, 0.6%-5.6% higher]). Individual quality measures had inconsistent associations with costs or LOS, but patients who had no quality measures missed had much shorter LOS and lower costs than those who missed even one., Conclusion: Avoiding lowest-volume hospitals and maximizing quality are separate approaches to improving health care efficiency through reducing costs of coronary bypass surgery.

This study presents constrained maximum likelihood derivations of the design parameters of noninferiority trials for binary outcomes with the margin defined on the odds ratio (ψ) or risk-difference (δ) scale. The derivations show that, for trials in which the group-specific response rates are equal under the point-alternative hypothesis, the common response rate, π(N), is a fixed design parameter whose value lies between the control and experimental rates hypothesized at the point-null, {π(C), π(E)}. We show that setting π(N) equal to the value of π(C) that holds under H(0) underestimates the overall sample size requirement. Given {π(C), ψ} or {π(C), δ} and the type I and II error rates, or algorithm finds clinically meaningful design values of π(N), and the corresponding minimum asymptotic sample size, N=n(E)+n(C), and optimal allocation ratio, γ=n(E)/n(C). We find that optimal allocations are increasingly imbalanced as ψ increases, with γ(ψ)<1 and γ(δ)≈1/γ(ψ), and that ranges of allocation ratios map to the minimum sample size. The latter characteristic allows trialists to consider trade-offs between optimal allocation at a smaller N and a preferred allocation at a larger N. For designs with relatively large margins (e.g. ψ>2.5), trial results that are presented on both scales will differ in power, with more power lost if the study is designed on the risk-difference scale and reported on the odds ratio scale than vice versa., (2010 John Wiley & Sons, Ltd.)

Personal health records (PHRs) are information repositories; however, PHRs may be less available to persons in the safety net setting. We deployed a free, secure, internet-based PHR for persons receiving care at the AIDS/HIV clinic at San Francisco General Hospital. In our initial rollout, 221 persons registered for the PHR. Compared to the entire clinic, these initial users were more likely to be Caucasian, male, non-Hispanic, on antiretroviral medications, and have better control of their HIV infection. The median number of online sessions was 7 and the median session length was 4 min. Laboratory results were the most commonly accessed feature. Patients were satisfied with the PHR and more than 80% of users agreed that the PHR helped them manage their medical problems; however, some users were concerned that their health information was not accurate or secure. Patients in a safety net setting will access and use an online PHR.

Objectives: We estimated the relative rate of highly credible gastrointestinal illness (HCGI) per year associated with active versus sham household water filtration devices among older adults in a community receiving tap water meeting current US standards., Methods: We conducted a randomized, triple-blinded, crossover trial in 714 households (988 individuals), which used active and sham water filtration devices for 6 months each. We estimated the annual incidence rate ratio of HCGI episodes and the longitudinal prevalence ratio of HCGI days at population and individual levels with a generalized estimating equation (GEE) and generalized linear mixed models (GLMMs), respectively, adjusted for covariates associated with outcome., Results: The incidence rate ratios (active versus sham) were 0.88 (95% confidence interval [CI] = 0.77, 1.00) and 0.85 (95% CI = 0.76, 0.94) HCGI episodes per year estimated by GEE and GLMM models, respectively. The corresponding longitudinal prevalence ratios were 0.88 (95% CI = 0.74, 1.05) and 0.84 (95% CI = 0.78, 0.90) HCGI days per person per year., Conclusions: We observed reductions in population- and individual-level measures of HCGI associated with use of the active filtration device. These findings suggest the need for further research on the impact of drinking water on the health of sensitive subpopulations.

Background: Care from high-volume centers or surgeons has been associated with lower mortality rates in coronary artery bypass surgery, but how volume and quality of care relate to each other is not well understood., Objective: To determine how volume and differences in quality of care influence outcomes after coronary artery bypass surgery., Design: Observational cohort., Setting: 164 hospitals in the United States., Patients: 81,289 patients 18 years or older who had coronary artery bypass grafting from 1 October 2003 to 1 September 2005., Measurements: Hospital and surgeon case volumes were estimated by using a data set. Quality measures were defined by whether patients received specific medications and by counting the number of measures missed. Hierarchical models were used to estimate effects of volume and quality on death and readmission up to 30 days., Results: After adjustment for clinical factors, lowest surgeon volume and highest hospital volume were associated with higher mortality rates and lower readmission risk, respectively. Patients who did not receive aspirin (odds ratio, 1.89 [95% CI, 1.65 to 2.16) or beta-blockers (odds ratio, 1.29 [CI, 1.12 to 1.49]) had higher odds for death, after adjustment for clinical risk factors and case volume. Adjustment for individual quality measures did not alter associations between volume and readmission or death. However, if no quality measures were missed, mortality rates at the lowest-volume centers (adjusted mortality rate, 1.05% [CI, 0.81% to 1.29%]) and highest-volume centers (adjusted mortality rate, 0.98% [CI, 0.72% to 1.25%]) were similar., Limitation: Because administrative data were used, the quality measures may not replicate measures collected through chart abstraction., Conclusion: Maximizing adherence to quality measures is associated with improved mortality rates, independent of hospital or surgeon volume., Primary Funding Source: California HealthCare Foundation.

Background: Millions of neonates undergo anesthesia each year. Certain anesthetic agents cause brain cell death and long-term neurocognitive dysfunction in postnatal day (P)7 rats. Despite its intuitive appeal, a causal link between cell death and neurocognitive decline after anesthesia has not been established. If one existed, the degree of cell death would be expected to correlate with the degree of neurocognitive dysfunction caused by anesthesia. The authors therefore tested if cell death caused by various durations of isoflurane at 1 minimum alveolar concentration causes duration-dependent long-term neurocognitive dysfunction., Methods: Isoflurane was administered to P7 rats at 1 minimum alveolar concentration for 0, 1, 2, or 4 h. To control for the respiratory depressant effects of anesthesia, a group of rats was treated with 4 h of carbon dioxide. Cell death was assessed by FluoroJade staining 12 h after the end of each intervention, and neurocognitive outcome was assessed 8 weeks later by using fear conditioning, spatial reference memory, and spatial working memory tasks., Results: Widespread brain cell death was caused by 2 h and 4 h of isoflurane and by 4 h of carbon dioxide. The degree and distribution of thalamic cell death was similar in 4 h isoflurane-treated and 4-h carbon dioxide-treated rats. Only 4 h of isoflurane caused a long-term neurocognitive deficit affecting both spatial reference memory and spatial working memory. Working memory was improved in carbon dioxide-treated rats., Conclusion: Isoflurane-induced brain cell death may be partly caused by hypercarbia. The inconsistencies between cell death and neurocognitive outcome suggest that additional or alternative mechanisms may mediate anesthesia-induced long-term neurocognitive dysfunction.

Objectives: Extracted teeth used in dental research need to be considered infective and hence be sterilized without the materials' properties being altered. This study examined the effect of gamma radiation on the nano-mechanical properties of dentin and enamel of extracted human third molars., Methods: Whole teeth were sterilized using gamma radiation doses of 7 kGy and 35 kGy, respectively; teeth of the control group were not treated with gamma radiation. Crowns were sectioned occlusally and polished. Elastic modulus and hardness were tested using atomic force microscopy with nano-indentations under wet conditions., Results: The authors found no significant dose-response relationship in elastic modulus or hardness in either dentin or enamel., Significance: Nano-indentation is a common technique for the determination of local mechanical properties in biological hard tissues. Gamma radiation is an efficient way to sterilize extracted teeth while alteration of dentin and enamel mechanical properties are minimized.

Background: Minocycline has anti-apoptotic and anti-inflammatory effects in vitro, and extends survival in mouse models of some neurological conditions. Several trials are planned or are in progress to assess whether minocycline slows human neurodegeneration. We aimed to test the efficacy of minocycline as a treatment for amyotrophic lateral sclerosis (ALS)., Methods: We did a multicentre, randomised placebo-controlled phase III trial. After a 4-month lead-in phase, 412 patients were randomly assigned to receive placebo or minocycline in escalating doses of up to 400 mg/day for 9 months. The primary outcome measure was the difference in rate of change in the revised ALS functional rating scale (ALSFRS-R). Secondary outcome measures were forced vital capacity (FVC), manual muscle testing (MMT), quality of life, survival, and safety. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00047723., Findings: ALSFRS-R score deterioration was faster in the minocycline group than in the placebo group (-1.30 vs -1.04 units/month, 95% CI for difference -0.44 to -0.08; p=0.005). Patients on minocycline also had non-significant tendencies towards faster decline in FVC (-3.48 vs -3.01, -1.03 to 0.11; p=0.11) and MMT score (-0.30 vs -0.26, -0.08 to 0.01; p=0.11), and greater mortality during the 9-month treatment phase (hazard ratio=1.32, 95% CI 0.83 to 2.10; p=0.23) than did patients on placebo. Quality-of-life scores did not differ between the treatment groups. Non-serious gastrointestinal and neurological adverse events were more common in the minocycline group than in the placebo group, but these events were not significantly related to the decline in ALSFRS-R score., Interpretation: Our finding that minocycline has a harmful effect on patients with ALS has implications for trials of minocycline in patients with other neurological disorders, and for how potential neuroprotective agents are screened for use in patients with ALS.

Unlabelled: Initiation of enamel formation requires reciprocal signaling between epithelially and mesenchymally derived cells., Objective: In this study, we used a transgenic mouse model which drives overexpression of an activated form of TGF-beta2 under control of the osteocalcin promoter, to investigate the role of TGF-beta2 in the dental mesenchyme, on enamel formation., Design: Dentin and enamel were imaged by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Dentin mechanical properties were characterized for hardness and elasticity, following nanoindentation with a modified AFM. Pores found in enamel were quantified and compared using image analysis software (Scion Imagetrade mark)., Results: The elastic modulus of dentin was significantly reduced in the male TGF-beta2 overexpressor mice as compared to male wildtype mice, with no significant differences between female mice. Similarly, there were significantly more pores in enamel of the male transgenic mice as compared to male wildtype mice, with no significant differences between female mice. In situ hybridization of the continuously erupting incisor confirmed that osteocalcin expression was limited to the odontoblast cell layer at all stages of tooth formation., Conclusion: TGF-beta2 overexpression in the dentin matrix, results in sex-linked differences in dentin and enamel formation.

Object: Obtaining brain biopsy specimens is often the diagnostic test of last resort for patients with unexplained neurological conditions, particularly those with a rapidly deteriorating neurological course. The goals of this analysis were to determine the diagnostic sensitivity of brain biopsy specimens in these types of patients and retrospectively identify features of these disorders that may have enabled an earlier diagnosis, which may prevent the need for diagnostic brain biopsy procedures in the future., Methods: The authors reviewed the case records of all brain biopsy procedures that had been performed at a single tertiary care institution between January 1993 and April 2002 in 171 patients. Patients with HIV or nonlymphomatous brain tumors were excluded from this analysis because the utility of brain biopsy specimens for these conditions has been determined front previous studies. A subgroup analysis of this cohort was performed in the 64 patients who had comprehensive medical records and a clinical syndrome involving a progressively deteriorating neurological condition of less than 1 year in duration. The overall sensitivity of brain biopsy procedures for diagnostic purposes in the cohort was 65% (111 of 171 patients). The two most common diagnoses in the subgroup with rapidly deteriorating neurological conditions were primary central nervous system (CNS) B-cell lymphoma in 20.3% (13 patients) and Creutzfeldt-Jakob disease in 15.6% (10 patients), followed by viral encephalitis in 14.1% (nine patients) and CNS vasculitis in 9.4% (six patients). Clinical symptoms and laboratory data were compared among the diagnostic groups., Conclusions: These results will help guide the evaluation of patients with neurological conditions that are difficult to diagnose and will provide a foundation for further prospective studies.

To better understand the design of noninferiority trials for binary data, we identify analogies and contrasts between this and the more familiar superiority trial design. We restrict attention to the problem of detecting a difference between experimental and control response rates in the setting where there is no difference (piE - piC = 0) under the noninferiority alternative hypothesis and under the superiority null, and a matching difference between groups under the complementary hypotheses (/piE - piC/ = delta). Our derivation of the constrained maximum likelihood estimates (MLEs) reveals that superiority and noninferiority trials have different nuisance parameters--the marginal response rate and the control-group response rate, respectively. Our empirical results show that when individuals are allocated to treatment groups in the ratio that minimizes the overall sample size, balanced allocation is optimal only for superiority trials when the error rates are equal; otherwise imbalanced allocation is optimal. Different allocation ratios between trial types lead to different variances, and thus to different sample sizes. Finally, since the value of the marginal response rate--a design parameter in noninferiority trials--typically cannot be obtained from preliminary or published studies, we suggest a means of identifying a value that can be used. We conclude that full documentation of the design of a trial requires specification not only of the design parameters but also of the allocation ratio and the nuisance parameter, the value of which is not obvious under unequal allocation.

Objective: This double-blinded, placebo-controlled clinical trial tested the safety and efficacy of a topical secretory IgA antibody manufactured in tobacco plants (plantibody) in preventing recolonization of mutans streptococci (MS) in human plaque as measured by whole stimulated saliva samples., Methods: Following a 9-day antimicrobial treatment with chlorhexidine (CHX), 56 eligible adults (enrollment salivary MS > or = 10(4) CFU/ml; no current caries) were randomized equally to a group receiving 0, 2, 4, or 6 topical applications of plantibody followed by 6, 4, 2, or 0 applications of placebo, respectively, over a 3-week period., Results: Among the 54 subjects who completed the trial, the CHX regimen eliminated salivary MS in 69%. After 6 months, there were no significant differences in MS levels by number of applications, relative to placebo (p > 0.43). No adverse effects were observed., Conclusion: Plantibody is safe but not effective at the frequency, concentration, and number of applications used in this study., (Copyright (c) 2005 S. Karger AG, Basel.)

Exposed root surfaces frequently exhibit non-carious notches representing material loss by abrasion, erosion, and/or abfraction. Although a contribution from mechanical stress is often mentioned, no definitive proof exists of a cause-effect relationship. To address this, we examined dimensional changes in dentin subjected to cyclic fatigue in two different pH environments. Human dentin cantilever-beams were fatigued under load control in pH = 6 (n = 13) or pH = 7 (n = 13) buffer, with a load ratio (R = minimum load/maximum load) of 0.1 and frequency of 2 Hz, and stresses between 5.5 and 55 MPa. Material loss was measured at high- and low-stress locations before and after cycling. Of the 23 beams, 7 withstood 1,000,000 cycles; others cracked earlier. Mean material loss in high-stress areas was greater than in low-stress areas, and losses were greater at pH = 6 than at pH = 7, suggesting that mechanical stress and lower pH both accelerate erosion of dentin surfaces.

Double-blinded trials are often considered the gold standard for research, but significant bias may result from unblinding of participants and investigators. Although the CONSORT guidelines discuss the importance of reporting "evidence that blinding was successful", it is unclear what constitutes appropriate evidence. Among studies reporting methods to evaluate blinding effectiveness, many have compared groups with respect to the proportions correctly identifying their intervention at the end of the trial. Instead, we reasoned that participants' beliefs, and not their correctness, are more directly associated with potential bias, especially in relation to self-reported health outcomes. During the Water Evaluation Trial performed in northern California in 1999, we investigated blinding effectiveness by sequential interrogation of participants about their "blinded" intervention assignment (active or placebo). Irrespective of group, participants showed a strong tendency to believe they had been assigned to the active intervention; this translated into a statistically significant intergroup difference in the correctness of participants' beliefs, even at the start of the trial before unblinding had a chance to occur. In addition, many participants (31%) changed their belief during the trial, suggesting that assessment of belief at a single time does not capture unblinding. Sequential measures based on either two or all eight questionnaires identified significant group-related differences in belief patterns that were not identified by the single, cross-sectional measure. In view of the relative insensitivity of cross-sectional measures, the minimal additional information in more than two assessments of beliefs and the risk of modifying participants' beliefs by repeated questioning, we conclude that the optimal means of assessing unblinding is an intergroup comparison of the change in beliefs (and not their correctness) between the start and end of a randomized controlled trial.

Objectives: This single-blind randomized controlled pilot study evaluated the efficacy of a behavioral intervention program, PRO-SELF: Candidiasis, to reduce time to recurrence of oral candidiasis over 6 months in susceptible HIV-seropositive persons. The intervention involved instruction by dentists on improving oral hygiene, minimizing sugar intake, and self-diagnosing candidiasis., Methods: Participants were adults with oral candidiasis responsive to antifungals who presented to the UCSF Stomatology Clinic between 1997 and 2000. At 2-3 weeks of follow-up visits, a dentist "examiner", masked to group assignment, quizzed participants as to the presence of candidiasis, and assessed candidiasis status. A second, unmasked dentist "instructor" then delivered the program to intervention participants. Participants recorded dietary and oral hygiene practices in 24-h recall diaries: intervention participants at each visit and controls at initial and final visits., Results: At randomization, CD4+ cell counts (cells/mm(3)) were 298 +/- 188 among 18 intervention participants and 396 +/- 228 among 17 controls. The candidiasis recurrence rates at 6 months were 78% among intervention compared with 88% among control participants (hazard ratio 0.72; 95% CI 0.35-1.50). Performing oral hygiene after meals/snacks showed the largest relative improvement: intervention-control difference in proportion of meals/snacks affected was 24% (95% CI -1 to 48%). Self-diagnoses of candidiasis were inaccurate, possibly because of mild episodes., Conclusions: The results weakly indicate that regular instruction from healthcare professionals helps patients delay candidiasis recurrence by improving oral hygiene. Among HIV-seropositive persons, those with poor oral hygiene, and high-sugar diets are most likely to benefit., (Copyright Blackwell Munksgaard, 2004)

Objective: To determine the effect of dentin smear layers created by various abrasives on the adhesion of a self-etching primer (SE) and total-etch (SB) bonding systems., Methods: Polished human dentin disks were further abraded with 0.05 micro m alumina slurry, 240-, 320- or 600-grit abrasive papers, # 245 carbide, # 250.9 F diamond or # 250.9 C diamond burs. Shear bond strength (SBS) was evaluated by single-plane lap shear, after bonding with SE or SB and with a restorative composite. Smear layers were characterized by thickness, using SEM; surface roughness using AFM; and reaction to the conditioners, based on the percentage of open tubules, using SEM., Results: Overall, SBS was lower when SB was used than when SE was used. SBS decreased with increasing coarseness of the abrasive in the SE group. Among burs, the carbide group had the highest SBS, and 320- and 240-grit papers had SBS close to the carbide group. Surface roughness and smear layer thickness varied strongly with coarseness. After conditioning with SE primer, the tubule openness of specimens abraded by carbide bur did not differ from 240- or 320-grit paper, but did differ from the 600-grit., Significance: Even though affected by different surface preparation methods, SE yielded higher SBS than SB. The higher SBS and thin smear layer of the carbide bur group, suggests its use when self-etching materials are used in vivo. Overall, the 320-grit abrasive paper surface finish yielded results closer to that of the carbide bur and its use is recommended in vitro as a clinical simulator when using the SE material.

Objective: To determine the efficacy of a spit tobacco (ST) intervention designed to promote ST cessation and discourage ST initiation among male high school baseball athletes., Methods: This study was a cluster-randomized controlled trial. Forty-four randomly selected high schools in rural California were randomized within strata (prevalence of ST use and number and size of baseball teams) to either the intervention or the control group. Ninety-three percent of eligible baseball athletes participated, yielding 516 subjects in 22 intervention schools and 568 subjects in 22 control schools. Prevalences of sustained ST cessation and ST use initiation over 1 year were assessed by self-report. Multivariate logistic regression models for clustered responses were used to test the null hypotheses of no association between group and the two outcomes, adjusted for the stratified design and baseline imbalances between groups in significant predictors of ST use., Results: Prevalence of cessation was 27% in intervention high schools and 14% in control high schools (odds ratio (OR)=2.29; 95% confidence interval (CI), 1.36-3.87). The intervention was especially effective in promoting cessation among those who, at baseline, lacked confidence that they could quit (OR=6.4; 95% CI, 1.0-4.3), among freshmen (OR=15; 95% CI, 0.9-260), and among nonsmokers (OR=3.2; 95% CI, 0.9-11). There was no significant difference between groups in the prevalence of ST initiation., Conclusions: This intervention was effective in promoting ST cessation, but was ineffective in preventing initiation of ST use by nonusers.

Glutamate formiminotransferase deficiency, an autosomal recessive disorder and the second most common inborn error of folate metabolism, is presumed to be due to defects in the bifunctional enzyme glutamate formiminotransferase-cyclodeaminase (FTCD). Features of a severe phenotype, first identified in patients of Japanese descent, include elevated levels of formiminoglutamate (FIGLU) in the urine in response to histidine administration, megaloblastic anemia, and mental retardation. Features of a mild phenotype include high urinary excretion of FIGLU in the absence of histidine administration, mild developmental delay, and no hematological abnormalities. We found mutations in the human FTCD gene in three patients with putative glutamate formiminotransferase deficiency. Two siblings were heterozygous for missense mutations, c.457C>T (R135C) and c.940G>C (R299P). Mutagenesis of porcine FTCD and expression in E. coli showed that the R135C mutation reduced formiminotransferase activity to 61% of wild-type, whereas the R299P mutation reduced this activity to 57% of wild-type. The third patient was hemizygous for c.1033insG, with quantitative PCR indicating that the other allele contained a deletion. These mutations are the first identified in glutamate formiminotransferase deficiency and demonstrate that mutations in FTCD represent the molecular basis for the mild phenotype of this disease., (Copyright 2003 Wiley-Liss, Inc.)

This research tested the hypothesis that active and arrested carious dentin lesions have distinct structural characteristics and differ in atomic force microscopy-based nano-mechanical properties of the identifiable zones found in hydrated coronal carious lesions. Eight carious molars were used in this study. After longitudinally bisecting all the samples through the centers of carious lesions, they were divided into two subgroups: moderately active caries and arrested caries. The samples were highly polished and stained by caries detector, which allowed identification of four zones: pink, light pink, transparent and apparently normal. The mechanical properties were studied wet using atomic force microscopy. The results show that both groups contained the same zones, regardless of activity status, and different zones have different mechanical properties. Generally, the more demineralized outer zones (pink, light pink) were larger and the mechanical properties of the zones were lower for moderately active caries. For arrested caries, the transparent zone occupied a larger portion of the lesion and the reduced elastic modulus was not significantly different from the underlying normal zone, although its hardness was lower than the apparently normal zone.

Objective: Dentin structure varies with orientation and location. Ultimate shear strength (USS) has also been found in previous studies to vary with location. The present study further explores this relationship between USS and various locations in coronal dentin as well as distance from the pulp., Methods: Stick specimens were prepared from coronal dentin located in the center or under cusps of human molar teeth. These were tested in the shear mode at various distances from the pulp., Results: Median values ranged from 52.7 (range 29.0-73.1) MPa near the pulp to 76.7 (range 53.9-104.0) MPa near the dentino-enamel junction. No differences were found among the buccal, central or lingual locations, however, the USS near the pulp was found to be significantly lower., Significance: The properties of coronal dentin vary with distance from the pulp, which may affect adhesion and other aspects of restorative dentistry., (Copyright 2002 Acadamy of Dental Materials)

Enamel fluorosis is characterised by increased porosity and a delay in the removal of enamel matrix proteins as the enamel matures. Amelogenin is the primary matrix protein in secretory-stage dental enamel. As enamel matures, amelogenins are hydrolysed by a number of enamel proteinases, including matrix metalloproteinase-20 (MMP-20 or enamelysin) and serine proteinase. Here, the effect of ingested fluoride on the relative activity of proteinases in the enamel matrix and the specific effect of fluoride on MMP-20 activity were examined. Proteinase activity relative to total enamel matrix protein was measured by fluorescence assay of enamel matrix dissected from rats given 0, 50, or 100 parts per 10(6) fluoride in their drinking water. To determine the specific effect of fluoride on the activity of MMP-20, the hydrolysis of a full-length recombinant human amelogenin by recombinant MMP-20 (rMMP-20) in the presence of 0, 2, 5, 10 or 100 microM fluoride was compared by sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis (PAGE). In addition, a fluorescent peptide assay was developed to quantify enzyme activity against the tyrosine-rich amelogenin peptide cleavage site. In the late maturation stage, total proteinase activity per unit protein was lower in the fluoride-exposed rats than in the control rats. This in vivo finding indicates that fluoride ingestion can alter the relative amount of active proteinase in mature enamel. Hydrolysis of amelogenin at neutral pH by rMMP-20 was reduced in the presence of 100 microM F. In the peptide assay, rMMP-20 activity was significantly reduced by concentrations of fluoride as low as 2 microM at pH 6, with no significant effect at pH 7.2. These in vitro assays show that micromolar concentrations of fluoride can alter metalloproteinase activity, particularly when the pH is reduced to 6.0. These studies suggest that the effects of fluoride on enamel matrix proteinase secretion or activity could be involved in the aetiology of fluorosis in enamel and other mineralising tissues.

Self-etching primers are thought to offer significant advantages over total-etch adhesive systems. The hypothesis tested in this study was that there was no difference in etching characteristics between a self-etching primer and a phosphoric acid solution at the same pH. Etching was assessed using atomic force microscopy (AFM) evaluation of site-specific changes in the height of the peritubular and intertubular dentin as a function of exposure time. Human dentin disks (n = 6/group), prepared with an acid-resistant glass reference layer, were etched with a self-etching primer and with 0.0134 M phosphoric acid (both pH approximately egual to 1.94). Depth changes relative to the reference layer were measured with the AFM after each etching interval, at 15 different locations, each in the peritubular and intertubular dentin. The total demineralization depth was measured in a scanning electron microscope. Peritubular dentin etching rate was linear while it could be measured (up to 15 s) and was greater for the self-etching primer (p < 0.0001). Intertubular dentin displayed a similar demineralization pattern with both acids, ultimately reaching a plateau in the majority of specimens. The self-etching primer attained a plateau after less recession than phosphoric acid (p < 0.0001). Dentin demineralization appears to be affected by other factors in addition to the pH of the etchant solutions.

This paper reviews five randomized controlled trials of brief spit (smokeless) tobacco (ST) cessation treatment by dental professionals consisting of oral cancer screening, cessation advice, self-help materials, and brief cessation counseling by a dental hygienist. In addition, original two-year findings from a randomized controlled trial to determine the effect of a dental-directed, peer-assisted ST intervention among high school baseball athletes in rural California (n=1084) are reported. In the latter study, results show sustained quitting at two years of 23 percent (32/141) in the intervention group and 13 percent (21/166) in the control group (OR=2.0, 95% CI 1.1-3.9) with subjects lost-to-follow-up considered non-quitters. The evidence presented supports the efficacy of oral screening and brief cessation counseling by dental professionals to promote ST cessation in the dental office or in athletic facilities. In addition, recommendations for policy and future research are presented.

Mutations in the MTR gene, which encodes methionine synthase on human chromosome 1p43, result in the methylcobalamin deficiency G (cblG) disorder, which is characterized by homocystinuria, hyperhomocysteinemia, and hypomethioninemia. To investigate the molecular basis of the disorder, we have characterized the structure of the MTR gene, thereby identifying exon-intron boundaries. This enabled amplification of each of the 33 exons of the gene, from genomic DNA from a panel of 21 patients with cblG. Thirteen novel mutations were identified. These included five deletions (c.12-13delGC, c.381delA, c.2101delT, c.2669-2670delTG, and c.2796-2800delAAGTC) and two nonsense mutations (R585X and E1204X) that would result in synthesis of truncated proteins that lack portions critical for enzyme function. One mutation was identified that resulted in conversion of A to C of the invariant A of the 3' splice site of intron 9. Five missense mutations (A410P, S437Y, S450H, H595P, and I804T) were identified. The latter mutations, as well as the splice-site mutation, were not detected in a panel of 50 anonymous DNA samples, suggesting that these sequence changes are not polymorphisms present in the general population. In addition, a previously described missense mutation, P1173L, was detected in 16 patients in an expanded panel of 24 patients with cblG. Analysis of haplotypes constructed using sequence polymorphisms identified within the MTR gene demonstrated that this mutation, a C-->T transition in a CpG island, has occurred on at least two separate genetic backgrounds.

Background and Objectives: The use of cannabinoids for appetite stimulation and the management of wasting and antiretroviral side-effects has become a common practice in the care of HIV-infected individuals. We present pharmacokinetic data from a randomized placebo-controlled study designed to evaluate the metabolic effects of smoked marijuana and dronabinol in HIV-infected patients receiving indinavir (IDV) or nelfinavir (NFV)., Methods: Subjects on stable regimens containing IDV 800 mg every 8 h (n = 28) or NFV 750 mg three time a day (n = 34) were randomized to one of three treatment arms: 3.95% THC marijuana cigarettes, dronabinol 2.5 mg capsules or placebo capsules administered three times daily. Serial blood sampling was performed at baseline and on day 14 of treatment. The changes in NFV and IDV pharmacokinetics were measured as the median percentage change from baseline., Results: At day 14, the 8-h area under the curve (AUC(8)) changed by -10.2% (P = 0.15), maximum concentration (C(max)) by -17.4% (P = 0.46), and minimum concentration (C(min)) by -12.2% (P = 0.28) for patients in the NFV marijuana arm (n = 11). Similar decreases had occurred by day 14 among patients in the IDV marijuana arm (n = 9): AUC8 had changed by -14.5% (P = 0.074), C(max) by -14.1% (P = 0.039), and C(min) by -33.7% (P = 0.65)., Conclusion: Despite a statistically significant decrease in C(max) of IDV in the marijuana arm, the magnitude of changes in IDV and NFV pharmacokinetic parameters in the marijuana arm are likely to have no short-term clinical consequence. The use of marijuana or dronabinol is unlikely to impact antiretroviral efficacy.

We conducted a randomized, triple-blinded home drinking water intervention trial to determine if a large study could be undertaken while successfully blinding participants. Households were randomized 50:50 to use externally identical active or sham treatment devices. We measured the effectiveness of blinding of participants by using a published blinding index in which values >0.5 indicate successful blinding. The principal health outcome measured was "highly credible gastrointestinal illness" (HCGI). Participants (n=236) from 77 households were successfully blinded to their treatment assignment. At the end of the study, the blinding index was 0.64 (95% confidence interval 0.51-0.78). There were 103 episodes of HCGI during 10,790 person-days at risk in the sham group and 82 episodes during 11,380 person-days at risk in the active treatment group. The incidence rate ratio of disease (adjusted for the clustered sampling) was 1.32 (95% CI 0.75, 2.33) and the attributable risk was 0.24 (95% CI -0.33, 0.57). These data confirm that participants can be successfully blinded to treatment group assignment during a randomized trial of an in-home drinking water intervention.

Dentin structure and properties are known to vary with orientation and location. The present study explored the variation in the ultimate tensile strength (UTS) of dentin with location in the tooth. Hourglass specimens were prepared from dentin located in the center, under cusps, and in the cervical regions of human molar teeth. These were tested in tension at various distances from the pulp. Median tensile strengths ranged from 44.4 MPa in the inner dentin near the pulp, to 97.8 MPa near the dentino-enamel junction (DEJ). This increase in the median UTS with distance from the pulp to the DEJ was statistically significant (P <.001). Of particular importance was the observation that the UTS measurements followed a Weibull probability distribution, with a Weibull modulus of about 4.5. The Weibull behavior of the UTS data strongly suggests that the large variances in fracture strength data result from a distribution of preexisting defects in the dentin. These findings justify a damage-mechanics approach to studies of dentin failure., (Copyright 2002 Wiley Periodicals, Inc.)

Objective: To determine if medical clinicians are as accurate as dental clinicians in recognizing diagnostic characteristics of HIV-related oral lesions., Methods: In 355 HIV-infected participants at five Women's Interagency HIV Study sites, we paired oral examinations conducted within 7 days of each other by dental and medical clinicians. We used the former as a gold standard against which to evaluate the accuracy of the latter. We assessed the accuracy of the medical clinicians' findings based both on their observations of abnormalities and on their descriptions of these abnormalities., Results: Dental clinicians diagnosed some oral abnormality in 38% of participants. When "abnormality" was used as the medical clinicians' outcome, sensitivities were 75% for pseudomembranous candidiasis and 58% for erythematous candidiasis, but only 40% for hairy leukoplakia. When a precise description of the abnormality was used as their outcome, sensitivities were 19%, 12% and 20%, respectively., Conclusions: Medical clinicians recognize that HIV-related oral abnormalities are present in 40-75% of cases, but less often describe them accurately. Low sensitivity implies that the true associations of specific oral lesions with other HIV phenomena, such as time until AIDS, must be stronger than the literature suggests.

Evaluating smoking prevention and cessation programs requires valid data collection. This study examined two survey modes--face-to-face (FTF) interview and self-administered questionnaire (SAQ)--comparing response rates, sample characteristics, data quality, and response effects. From two family planning clinics, 601 female Latina and African American clients ages 12 to 21 were recruited and randomized to either group. Results reveal that neither mode is superior to the other. The SAQ may therefore be preferable for this population, despite its higher rate of incompletes, because it yields results similar to the FTF yet is more cost effective and less disruptive to clinic routines.

Although oral candidiasis lesions are widely recognized as markers for AIDS, the relative prognostic significance of functions of these episodes has not been examined. We compare the associations with time to AIDS of one fixed and six time-dependent metrics of oral candidiasis lesions, including proximity of a lesion to seroconversion, any candidiasis history, and recency of a lesion. We show in Cox regression models that two metrics are clinically and statistically far more significant than the others, alone or in combination: any history of candidiasis since HIV seroconversion, and recency of a candidiasis episode. The latter metric indicates that the risk of an AIDS diagnosis is high during a candidiasis episode. The results hold for two cohorts of male seroconverters, 627 haemophiliacs and 196 men who have sex with men. Identification of highly prognostic functions of a patient's oral candidiasis history allows clinicians and researchers to focus on these aspects of the history and to omit extraneous information from data collection. Our method extends well beyond candidiasis and AIDS, and may shed light on associations of covariates with outcomes in a variety of settings., (Copyright 2000 John Wiley & Sons, Ltd.)

Objective: To describe the incidence and prevalence of oral manifestations of HIV infection in a population of perinatally infected children., Design: Retrospective and prospective study of a cohort of perinatally HIV-infected children., Setting: Community hospital and community-based paediatric clinic., Sample and Methods: Forty perinatally HIV-infected children with a median age of 12 months were eligible and selected for the study, which included a medical chart review from birth and prospective follow-up. Each child was examined quarterly for oral manifestations, tooth eruption, and for 27 children, caries and periodontal status., Results: The incidence of pseudomembranous candidiasis was 43% (95% CI, 27-58%) within 6 months of birth. Oral candidiasis (defined as pseudomembranous or erythematous) was positively associated with low CD4 counts and the occurrence of plaque. Children with low CD4 counts were also found to have fewer teeth than children with high CD4 counts, after adjusting for age., Conclusions: Oral manifestations are common in paediatric HIV infection and are possible predictors of HIV disease progression. Primary care of HIV-infected children should include periodic oral examinations to monitor their HIV disease progression and to alleviate symptoms associated with oral opportunistic infections.

Objective: To describe the prevalence, patterns, and correlates of spit (smokeless) tobacco (ST) use in a sample of high school baseball athletes in California., Design: This cross sectional study was a survey of 1226 baseball athletes attending 39 California high schools that were randomly selected from a list of all publicly supported high schools with baseball teams. At a baseball team meeting, athletes who agreed to participate and had parental consent completed the study questionnaire. To enhance the accuracy of self reported ST use status, a saliva sample was collected from each subject. The questionnaires and saliva samples were coded and salivary cotinine assay was performed on a random subsample of 5% of non-users who also were non-smokers. Biochemical assay indicated that 2% tested positive for cotinine inconsistent with self reported ST non-use., Results: Overall, 46% had ever used ST and 15% were current users. Odds ratios and 95% confidence intervals (CI) suggested that, among high school baseball athletes, age, living in a rural area, being white, smoking cigarettes, drinking alcohol, not knowing about the adverse effects of ST, perceiving little personal risk associated with ST use, and believing that friends, role models, teammates, and same age baseball athletes in general used ST, increased the likelihood of being an ST user., Conclusion: The findings indicate that considerable experimentation with ST products occurs among high school baseball athletes in California, and many are current users. ST interventions targeting this population are needed to stop the transition from experimental ST use to tobacco dependence. Correlates of ST use for consideration in future intervention studies are identified.

Objectives: The purpose of this study was to determine the efficacy of a college-based smokeless tobacco cessation intervention targeting college athletes., Methods: Sixteen colleges were matched for prevalence of smokeless tobacco use in their combined baseball and football teams and randomly assigned within college pairs to the intervention or the control group. One-year prevalence of cessation among smokeless tobacco users was determined by self-report of abstinence for the previous 30 days. Differences between groups were analyzed in a weighted version of the Fisher 1-sided permutation test for paired samples after adjustment for significant predictors of quitting other than the intervention (i.e., smokeless tobacco uses per week and most frequently used brand)., Results: Cessation prevalences were 35% in the intervention colleges and 16% in the control colleges when subjects with unknown quit status were defined as nonquitters. After adjustment for other significant predictors of quitting, the difference of 19% increased to 21%. The intervention effect increased with level of smokeless tobacco use., Conclusions: This intervention was effective in promoting smokeless tobacco cessation, especially among those who were more frequent users.

Sixteen colleges were matched on the baseline prevalence of spit tobacco (ST) use, and college pairs were randomized, one to the intervention and the other to the control group. Baseball and football athletes at each intervention college received: an oral examination by a dental professional who pointed out ST-related problems in the athlete's mouth and advised him to quit ST use; counseling by a dental hygienist on strategies to cope with cravings and triggers for use; and two follow-up telephone calls. At the three-month follow-up, quit rates were 24% and 16% for the intervention (n = 171) and control (n = 189) groups, respectively (p < 0.05). As the reported amount of ST used weekly increased, the percent of individuals who quit at 3 mos decreased (p < 0.05). Dental professionals appear to be effective in promoting spit tobacco cessation at 3 mos post-intervention in male college athletes, especially among those using lesser amounts of ST.

To determine whether the presence of specific oral lesions is associated with cigarette smoking among HIV-infected patients, we analyzed cross-sectional data (CD4 cell count, smoking history, and oral examination findings) from 1,058 HIV-infected male patients who received clinical care at the University of California, San Francisco. Oral AIDS Center Clinic. To control for potential confounding by the level of immune suppression, final analyses were limited to participants (n = 693) on whom CD4 cell count data (within 180 days of study visit) were available. Six percent of subjects had normal examination findings, 16% had nonnormal findings (but none of the six lesions of interest), 47% had lesions of a single type, and 31% had a combination of two or more types of lesions. After adjusting for CD4 cell count, current smokers were significantly more likely to have candidiasis (odds ratio [OR] = 1.84; 95% confidence interval [CI] 1.34-2.54) and warts (OR = 2.09; 95% CI 1.15-3.81) and less likely to have aphthous ulcers (OR = 0.24; 95% CI 0.14-0.42) than were current nonsmokers. These results suggest a strong association between cigarette smoking and the presence of specific HIV-related oral lesions.

Performances of anti-nuclear antibody testing by immunofluorescence assay (ANA-IFA) and enzyme immunoassay (ANA-EIA) were compared in relation to patient diagnosis. A total of 467 patient serum samples were tested by ANA-IFA (Kallestad; Sanofi) and ANA-EIA (RADIAS; Bio-Rad), and their age, sex, diagnosis, disease status, and medications were obtained through chart review. Reference ranges were established by testing 98 healthy blood donor samples. Eighty-six samples came from patients with diffuse connective tissue diseases, including systemic lupus erythematosus, discoid lupus erythematosus, or drug-induced lupus (n = 71); systemic sclerosis, CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal motility abnormalities, sclerodactyly, and telangiectasia), or Raynaud's syndrome (n = 8); Sjögren's syndrome (n = 5); mixed connective tissue disease (n = 5); and polymyositis or dermatomyositis (n = 3). The sensitivity, specificity, positive predictive value, and negative predictive value for ANA-IFA were 87.2, 48.0, 29.1, and 93.9%, respectively, for the reference range of < 1:160. For ANA-EIA, they were 90.7, 60.2, 35.8, and 96.4%, respectively, for the reference range of < 0.9. ANA-EIA offers equivalent sensitivity and higher specificity compared to ANA-IFA.

The authors used multivariate repeated-measures transition models to identify risk factors for two oral lesions related to human immunodeficiency virus (HIV)-candidiasis and hairy leukoplakia-in 152 HIV-infected blood transfusion recipients and hemophiliacs. Subjects were examined for occurrences of these lesions every 6 months from July 1985 through March 1993, yielding 1,076 study visits. It was found that, after adjustment for the CD4:CD8 T-lymphocyte ratio, patients with a history of candidiasis in the previous 18 months were at high risk of lesion recurrence. This risk increased with the number of prior episodes and with the recency of the episode(s). A history of hairy leukoplakia was less predictive of persistence of that lesion after adjustment for significant risk factors (including candidiasis and use of antifungal agents at the current examination, a low CD4:CD8 cell ratio, and age less than 40 years). The authors also found a high coprevalence of candidiasis and hairy leukoplakia in these subjects. These results suggest that HIV-infected patients with oral candidiasis should be carefully monitored for subsequent episodes over the next 12-18 months, and patients with either oral candidiasis or hairy leukoplakia and a low CD4:CD8 cell ratio should be carefully examined for the other type of lesion as well.

To determine whether daily use of nystatin pastilles can prevent initial outbreak or recurrence of oral candidiasis in HIV-infected patients and to identify factors associated with outbreaks during 20-week follow-up, a randomized, double-blind, placebo-controlled clinical trial was conducted. Subjects were 128 HIV-infected men (aged 27-60 years) who either had had no documented episode of oral candidiasis in the previous year or had been clinically clear of oral candidiasis for at least 72 h before randomization. Study arms were two placebo pastilles, one nystatin (200,000 U) and one placebo pastille, or two nystatin pastilles daily for 20 weeks. The main outcome measure was time to oral candidiasis, as determined by potassium hydroxide (KOH) smear and fungal culture. A multivariate proportional hazards model showed that four factors were significant (p < 0.001) in predicting time to oral candidiasis: nystatin treatment (hazard ratio 0.59), history of oral candidiasis (3.58), Candida albicans carriage (2.79), and CD4 count at randomization (0.65). In this small group of subjects, nystatin appeared to be effective in delaying onset of oral candidiasis. Patients with CD4 counts < 200 who are carriers of C. albicans and have a history of oral candidiasis may be most likely to benefit from antifungal prophylaxis.

In two-sample studies with ordinal responses, the Wilcoxon rank-sum test is generally chosen to test equality of the distributions, in spite of it being a specific test of location shift. I compared the power of the exact tests based on the Wilcoxon statistic, O'Brien's generalized Wilcoxon statistic, and the omnibus Smirnov statistic in the presence of location shift and scale alternatives. All three tests can gain power as a function of the scale parameter, depending on its magnitude relative to the shift parameter. As the relative influence of the scale parameter grows, the O'Brien test is the most powerful. I also compared the power of the asymptotic Wilcoxon test with its exact version, and found that it either inflates or deflates power if there are scale changes present. I present results of a simulation study.

The incidence of human papillomavirus (HPV)-related cervical intraepithelial neoplasia (CIN) and cervical cancer is increased with immunodeficiency, but the role of immune response, including cell-mediated immunity, in disease prevention is not well understood. In this study, T-cell proliferative responses to six synthetic peptides with predicted immunogenic determinants from the HPV-16 E4, E6, E7, and L1 open reading frames were analyzed in 22 sexually active women with new-onset CIN and 65 sexually active women without cervical disease, characterized by cytology, colposcopy, and HPV testing. T-cell proliferative responses were demonstrated to all six HPV-16 peptides. Although not statistically significant, rates of reactivity to E6 (24-45) were higher among sexually active women without disease (26%) than among women with current CIN (7%), as was the overall number of peptides stimulating a response. Women with CIN may not respond to selected HPV antigens as well as women without disease do.

A retrospective review of the medical records of 492 children perinatally exposed to the human immunodeficiency virus (HIV) compared the prevalence of orofacial soft-tissue manifestations in HIV-infected and noninfected children, identified risk factors for occurrence of orofacial lesions in HIV-infected children, and investigated specific orofacial lesions as indicators of progression of HIV disease. Application of eligibility criteria and the Centers for Disease Control classification of pediatric HIV infection resulted in selection of a study group of 91 HIV-positive children and a control group of 185 HIV-seronegative children who had seroreverted. Analysis of oral lesions showed that 67% of the study group and 8% of the control group had oropharyngeal candidiasis (OPC), 4% of the study group and 0% of the control group had parotid enlargement, and 3% of the study group and 0% of the control group had herpes simplex; all three differences were significant at P < 0.04. No statistically significant association was found between OPC and the risk factors of gender, ethnicity, or mode of delivery (vaginal versus cesarean). However, OPC was associated significantly with all progression markers examined: failure to thrive, use of antiretroviral agents, lower CD4 counts, and development of acquired immunodeficiency syndrome (AIDS). Orofacial manifestations are common in pediatric HIV infection and may serve as markers of infection and predictors of progression of HIV disease to AIDS.

Diagnostic tests may be necessary to determine the cause of oral ulcers. Direct immunofluorescence staining of oral smears supplies results much more quickly than viral culture, the "gold standard" for diagnosing HSV lesions. This study compares the sensitivity and specificity of direct immunofluorescence staining vs. viral culture and evaluates the usefulness of the two techniques for the general dental practitioner.

The goals of this study were to compare the prevalence of oral lesions in women infected with human immunodeficiency virus (HIV) and HIV-negative women, and to determine the association of oral lesions with route of HIV transmission and with level of immunosuppression in infected women. As part of a prospective 4-year study, oral examinations and blood tests were performed, at 6-month intervals, on 176 HIV-infected women and on 117 HIV-negative women at risk for HIV infection. We evaluated participants for the following oral conditions: hairy leukoplakia, candidiasis, ulcers, warts, non-Hodgkin's lymphoma, Kaposi's sarcoma, and parotid enlargement. As previously reported in men, the prevalence of oral lesions was significantly higher among HIV-infected (22%) than HIV-negative women (3%) [odds ratio (OR) = 8.2; 95% confidence interval (CI) 2.8, 23.5], particularly candidiasis (14%) and hairy leukoplakia (10%). Among HIV-infected women with CD4 cell count nadir > or = 200 cells/microliters, the prevalence of hairy leukoplakia was higher among those infected heterosexually than among injection drug users (OR = 5.5; 95% CI: 1.5; 19). The OR for the association between oral lesions and CD4 cell count nadir (< 200 vs. > 500 cells/microliters) was 8.9 (95% CI: 2.6, 30), indicating a strong positive association with level of immunosuppression.

We examine the relationship between beliefs regarding spit tobacco (ST) use and addiction among 473 male college athletes who currently use ST. Beliefs were assessed using methods prescribed by the Theory of Reasoned Action. Independent associations between beliefs and addiction, defined by self-reported amount of ST used per week, were found via multivariate polychotomous regression modeling. We found that with increasing addiction level, athletes were significantly more likely to believe that "ST helps me relax," "ST keeps me alert," "ST tastes good," and "ST is addicting." All athletes believed that clinicians, parents, and girlfriends do not approve of their ST use, but that male peers, coaches, and professional athletes are fairly indifferent about it. To increase quit rates, highly addicted ST users may require an intensive cessation program including nicotine replacement to overcome symptoms of withdrawal, oral substitutes for the enjoyable taste of ST, and the support of male peers and athletes who influence their social norms.

We surveyed varsity athletes (N = 1,328) in 16 California colleges about their patterns of spit (smokeless) tobacco (ST) use, related habits, reasons for use, and preferred methods for quitting. Prevalence of use was analyzed by sport and demographic characteristics, and patterns of use in players using snuff exclusively, using chewing tobacco exclusively, and those using both were compared. Odds ratios and 95% confidence intervals were calculated, adjusting for ethnic group. Prevalence was highest in Whites (44%) and Native Americans (48%) and lowest in African Americans (11%), and higher in varsity baseball (52%) than varsity football players (26%), in players attending rural colleges, and among those who ever smoked cigarettes or used alcohol. Forty-one percent of ST users initiated regular use during their high school years. Athletes who used snuff exclusively used it more intensively and for more years than those who used chewing tobacco exclusively. Snuff users indicated a greater perceived need for ST, but also were more ready to quit. These data suggest ST programs with prevention and cessation components are appropriate for high school as well as college athletes. Such interventions should focus on baseball players, distinguish snuff from chewing tobacco users in planning quit strategies, integrate intervention programs for cigarette smoking and alcohol consumption, provide training in refusal skills, and attempt to change social norms in support of ST use by integrating popular peers and significant others (e.g., wives/girlfriends) to endorse nonuse of ST.

Objective, reliable, and valid diagnostic criteria are required for studies of HIV-associated periodontal conditions. A set of diagnostic criteria were devised based on a literature review and the clinical experience of the authors. Validity was assessed by comparison with clinical photographs and the criteria were evaluated and refined for ease of use and objectivity. To assess the reliability of the criteria, 9 experienced examiners were shown 20 clinical photographs accompanied by brief vignettes of clinical information. Each examiner was asked to identify signs evident in a particular area of the photograph and to record a diagnosis. Five examiners were then trained and calibrated in the use of the criteria. Finally, all 9 examiners were shown the original 20 photographs and asked to identify signs and record diagnoses. The examiners showed only fair reliability in the recognition of clinical signs, made diagnoses intuitively, and had only fair agreement on the diagnosis of periodontal diseases. The inter-examiner reliability of examiners trained and calibrated in the use of the criteria increased and was greater than among untrained examiners. Rigid diagnostic criteria are essential in epidemiologic studies. Inter-examiner reliability will be increased if examiners are trained in their use and calibrated in the recognition of clinical signs. Diagnostic criteria should be modified as understanding of the diseases they classify increases. The proposed criteria will enhance the value of studies of HIV-associated periodontal changes and will contribute to that understanding.

Objectives: We evaluated time from HIV seroconversion to diagnosis of two common oral lesions associated with HIV infection and disease progression., Design: Oral examinations were performed on homosexual and bisexual men enrolled in prospective cohorts., Setting: Homosexual and bisexual men were followed in three epidemiologic cohort studies in San Francisco, California, USA., Participants: Data were evaluated from 80 men with well-defined dates of HIV seroconversion from 1984 through 1991., Main Outcome Measures: We determined the cumulative incidence of oral candidiasis and hairy leukoplakia after HIV seroconversion., Results: Four per cent of men developed oral candidiasis within 1 year after HIV seroconversion, 8% within 2, 15% within 3, 18% within 4, and 26% within 5 years. Nine per cent developed hairy leukoplakia within 1 year, 16% within 2, 25% within 3, 35% within 4, and 42% within 5 years. The median CD4+ count was 391 x 10(6)/l when oral candidiasis was first reported and 468 x 10(6)/l when hairy leukoplakia was first reported., Conclusions: Oral candidiasis or hairy leukoplakia appeared in a significant proportion of HIV-infected homosexual and bisexual men. These lesions occurred relatively soon after HIV seroconversion, typically before AIDS. Evaluation of HIV-infected individuals for these lesions has many potential clinical and research benefits, including the possible use of oral lesions as primary end-points in clinical trials.

Gross cystic disease fluid protein 15 (GCDFP-15) is universally present in the apocrine metaplastic epithelium of cystic breast disease and breast cancer, but it is rarely found in normal breast epithelium. Therefore GCDFP-15 detected in nipple aspirates of breast fluid (NAF) could serve as a biochemical marker of the presence and possibly extent of apocrine metaplasia within the breast. GCDFP-15 levels were measured in NAF from 37 Asian and 78 non-Asian women using radioimmunoassay. GCDFP-15 (range, 0-81,643 micrograms/ml) was found in the NAF of all but 1 woman and was highly correlated between right and left breasts. Mean concentrations of GCDFP-15 were significantly lower in NAF from Asian compared with non-Asian women. Markedly reduced levels of GCDFP-15 were found in the 17 women who had been parous in the previous 2 years. In women not parous within the prior 2 years, no relationship was found between GCDFP-15 levels and age, weight, age at menarche, first-degree family history of breast cancer, parity, oral contraceptive use, or smoking history. High concentrations of GCDFP-15 were found in the NAF of women with a history of a benign breast biopsy. Because similarly high levels of GCDFP-15 were found in NAF in over 40% of women without a history of benign breast biopsy, and because GCDFP-15 in the breast is produced only by apocrine metaplastic epithelium, we infer that the breasts of these women likely contain a significant degree of apocrine metaplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Background and Objectives: Sexually active adolescents, especially those in detention, are at high risk for acquisition of sexually transmitted diseases (STDs), including HIV infection. Yet little information is available that describes their risk behaviors associated with STDs. The overall objective was to define the relationship between risk behaviors and STD acquisition among adolescents., Goals of This Study: The first goal was to characterize drug use and sexual behaviors that place a population of adolescent male detainees at STD/HIV risk. The second goal was to define possible interrelationships between drug use, especially alcohol use, and risky sexual behaviors with STD acquisition., Study Design: The study group consisted of 414 adolescent male detainees 12 to 18 years of age who participated in an interview and a clinical assessment. Two hundred sixty-nine of the 414 subjects agreed to STD laboratory tests, including serologic testing for hepatitis B and syphilis, and urethral cultures to screen for chlamydial and gonorrheal urethritis., Results: Results showed that 15% had current evidence of at least one STD, and 34% had a history or current evidence of at least one STD (STD occurrence). The subjects were frequently engaging in risky sexual and drug use behaviors. Two multivariate models described three factors that significantly place the male adolescent in detention at risk for STDs: multiple sexual partners, inconsistent condom use, and the quantity of alcohol consumed per week., Conclusion: Youth in detention place themselves at risk for STDs including HIV because of their risky sexual behavior and drug use. Addressing alcohol use and barriers to condom use appear to be essential components of any STD prevention program targeting this largely minority youth population.