Innate recognition of apoptotic cells: novel apoptotic cell-associated molecular patterns revealed by crossreactivity of anti-LPS antibodies.

Cells dying by apoptosis are normally cleared by phagocytes through mechanisms that can suppress inflammation and immunity. Molecules of the innate immune system, the pattern recognition receptors (PRRs), are able to interact not only with conserved structures on microbes (pathogen-associated molecular patterns, PAMPs) but also with ligands displayed by apoptotic cells. We reasoned that PRRs might therefore interact with structures on apoptotic cells - apoptotic cell-associated molecular patterns (ACAMPs) - that are analogous to PAMPs. Here we show that certain monoclonal antibodies raised against the prototypic PAMP, lipopolysaccharide (LPS), can crossreact with apoptotic cells. We demonstrate that one such antibody interacts with a constitutively expressed intracellular protein, laminin-binding protein, which translocates to the cell surface during apoptosis and can interact with cells expressing the prototypic PRR, mCD14 as well as with CD14-negative cells. Anti-LPS cross reactive epitopes on apoptotic cells colocalised with annexin V- and C1q-binding sites on vesicular regions of apoptotic cell surfaces and were released associated with apoptotic cell-derived microvesicles (MVs). These results confirm that apoptotic cells and microbes can interact with the immune system through common elements and suggest that anti-PAMP antibodies could be used strategically to characterise novel ACAMPs associated not only with apoptotic cells but also with derived MVs.

Characterization of ß-adrenoceptor-mediated relaxation signals in isolated pulmonary artery of Dahl salt-sensitive hypertensive and normotensive rats.

1 Relaxant responses to isoprenaline (ISO) were studied in the pulmonary arteries of normotensive and hypertensive Dahl salt-sensitive rats. Rats were fed either a high-salt (4.0%) or low-salt (0.14%) diet for 5 weeks. Animals fed a high-salt diet (167/123±2/2 mmHg) had a significantly higher blood pressure compared to those fed a low-salt diet (127/87 ± 2/2 mmHg). 2 Isoprenaline-elicited relaxations were not significantly different in tissues from hypertensive compared to normotensive animals. Responses to ISO were significantly attenuated in denuded tissues and substantially more so in hypertensive compared to normotensive animals. While relaxant responses to ISO were resistant to inhibition by Nω-nitro-L-arginine methyl ester, indomethacin, glibenclamide or a combination of barium chloride and ouabain, they were inhibited by Rp-cAMP, anandamide and acidic buffer. The inhibitory impact of anandamide and acidic buffer was significantly greater in tissues from hypertensive vs. normotensive rats. 3 The resting membrane potential (Em) of smooth muscle cells was -67.0±0.7 mV (n=43 cells) and -66.6±0.8 mV (n=55 cells) in pulmonary arteries from hypertensive and normotensive rats, respectively. Isoprenaline produced hyperpolarization of E(m) which was significant in the blood vessels of hypertensive (-71.6±0.8 mV; n=29 cells) but not normotensive (-68.1±0.7 mV; n=49 cells) rats. 4 The endothelium plays a critical role in ß-adrenoceptor-mediated relaxation but nitric oxide is not the mediator for the response. It is possible that the greater hyperpolarization caused by ISO in blood vessels from hypertensive compared to normotensive rats is mediated by activation of TASK-1 channels.

Gender differences in associations between depressive symptoms and patterns of substance use and risky sexual behavior among a nationally representative sample of U.S. adolescents.

OBJECTIVE: This study uses a cluster analysis of adolescents, based on their substance use and sexual risk behaviors, to 1) examine associations between risk behavior patterns and depressive symptoms, stratified by gender, and 2) examine gender differences in risk for depression. METHODS: Data are from a nationally representative survey of over 20,000 U.S. adolescents. Logistic regression was used to examine the associations between 16 risk behavior patterns and current depressive symptoms by gender. RESULTS: Compared to abstention, involvement in common adolescent risk behaviors (drinking, smoking, and sexual intercourse) was associated with increased odds of depressive symptoms in both sexes. However, sex differences in depressive symptoms vary by risk behavior pattern. There were no differences in odds for depressive symptoms between abstaining male and female adolescents (OR = 1.07, 95% CI 0.70-1.62). There were also few sex differences in odds of depressive symptoms within the highest-risk behavior profiles. Among adolescents showing light and moderate risk behavior patterns, females experienced significantly more depressive symptoms than males. CONCLUSIONS: Adolescents who engage in risk behaviors are at increased risk for depressive symptoms. Girls engaging in low and moderate substance use and sexual activity experience more depressive symptoms than boys with similar behavior. Screening for depression is indicated for female adolescents engaging in even experimental risk behaviors.

Regulation of prolactin receptor expression in ovine skin in relation to circulating prolactin and wool follicle growth status.

Seasonal patterns of hair growth are governed, at least in part, by levels of prolactin in circulation, and although receptors for prolactin (PRLR) have been demonstrated in hair follicles, little is known of their regulation in relation to follicular cycles. In this study, a photoperiod-generated increase in prolactin was used to induce a wool follicle cycle during which changes in PRLR expression in sheep skin were determined by ribonuclease protection assay and in situ hybridisation. mRNA for prolactin and both isoforms of PRLR were also detected in skin by reverse transcription and polymerase chain reaction. As circulating prolactin began to rise from low levels, PRLR mRNA in the skin initially fell. These changes immediately preceded the catagen (regressive) phase of the hair cycle. Further increase in prolactin resulted in up-regulation of PRLR during telogen (dormancy), particularly in the epithelial hair germ, to reach a peak during proanagen (reactivation). In anagen (when follicle growth was fully re-established), PRLR mRNA returned to levels similar to those observed before the induced cycle. Hence, this longer term rise and fall of PRLR expression followed that of plasma prolactin concentration with a lag of 12-14 days. PRLR mRNA was most abundant in the dermal papilla, outer root sheath, hair germ, skin glands and epidermis. Location of PRLR in the dermal papilla and outer root sheath indicates action of prolactin on the growth-controlling centres within wool follicles. These cycle-related patterns of PRLR expression suggest dynamic regulation of PRLR by prolactin, thereby modulating hormonal responsiveness of seasonally growing hair follicles.

Characterization of the DGAT1 gene in the New Zealand dairy population.

Recently, DGAT1 was identified as the gene that underlies the QTL for bovine milk production on chromosome 14. This study investigated the effect of the reported polymorphism in three dairy breeds in New Zealand. Statistically significant results were identified for milk fat, milk protein, and volume for Jersey and Holstein-Friesian breeds, and only milk volume for Ayrshires. The average allele substitution effects were 2 to 3 kg of protein and 120 to 130 l milk for both the Jersey and Holstein-Friesian breeds. For milk fat, the average allele substitution effect was 6 kg for Holstein-Friesians and 3 kg for Jerseys. In all breeds, where the polymorphism increased milk fat yield, it decreased milk protein yield and milk volume.

Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infection in pediatric private practice.

BACKGROUND: Universal screening of sexually active adolescents for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) has been recommended in settings in which prevalence is 2% or greater. Although believed to be above 2%, the prevalence of CT and GC infection in private practice settings has not been clearly established and may affect screening practices. OBJECTIVES: To determine CT and GC infection prevalence in 2 pediatric private practices. DESIGN: Cross-sectional study. SETTING: Two pediatric private practices in suburban North Carolina. PATIENTS: Convenience sample of patients aged 15 to 24 years who were seen from August 1998 through June 1999. MAIN OUTCOME MEASURES: Prevalence of CT and GC infection. RESULTS: Of 1114 eligible patients, 803 (72%) completed questionnaires and provided urine specimens tested for CT and GC infection using ligase chain reaction assays. Mean age was 17.1 years (standard deviation: 1.8). Most participants were female (63%), white (87%), and from highly educated families (64% of their mothers graduated from college). Sexual activity was reported by 41%. Prevalence of CT infection in all participants was 0.9% (confidence interval [CI]: 0.4%-1.8%); in sexually active participants, 2.1% (CI: 0.9%-4.3%); in sexually active females, 2.7% (CI: 1.0%-5.7%); and in sexually active males, 0.9% (CI: 0.0%-5.1%). One case of GC infection was found. CONCLUSIONS: The prevalence of CT and GC infection in this private practice population was much lower than reported in other settings. Screening recommendations may need to be reassessed if other low prevalence populations are found.

Adolescents' interpretations of conditional confidentiality assurances.

PURPOSE: To improve physicians' discussions of confidentiality policies with adolescent patients. METHOD: Fifty-three students completed private semistructured interviews designed to explore adolescents' interpretations of a statement explaining both the protections and limitations of confidentiality. RESULTS: Results suggest strategies for explaining conditional confidentiality in a way adolescents' understand and trust.

The AMA Residency Training in Adolescent Preventive Services Project: report of the working group. The American Medical Association.

PURPOSE: To improve resident education in provision of adolescent preventive health care. The American Medical Association (AMA) Residency Training in Adolescent Preventive Services Project Working Group convened to identify specific goals and objectives (G&Os) for pediatric and family medicine resident education in adolescent clinical preventive services and recommend strategies to achieve these G&Os. METHODS: Iterative review process involving members of the working group, nine experienced teaching faculty and 16 resident physicians from family medicine and pediatric training programs, and an advisory board. RESULTS: We achieved consensus on appropriate G&Os for pediatric and family medicine residency education in adolescent clinical preventive services. Faculty and residents expressed concerns about achieving G&Os because of challenges to implementing effective training and evaluation strategies. Suggestions for achieving G&Os included development of an adolescent clinical preventive services curriculum and evaluation program that could be adapted for use in a variety of training program structures. Faculty and residents anticipated the success of a training curriculum would be influenced by: (a) availability of adequate numbers of skilled teaching faculty; (b) availability of time and support for faculty development and teaching efforts; and (c) exposure of residents to adequate numbers of adolescent patients in settings where there are clear expectations for delivery of comprehensive preventive services. CONCLUSIONS: The AMA Residency Training in Adolescent Preventive Services Project Working Group presents G&Os for organizing training experiences in adolescent clinical preventive services in family medicine and pediatric residency training programs and recommends strategies to achieve these G&Os.

Dietary vitamin C supplementation lowers blood pressure in spontaneously hypertensive rats.

In spontaneously hypertensive rats (SHRs) excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing cytosolic free calcium and blood pressure. The thiol compound, N-acetyl cysteine, normalizes elevated blood pressure in SHRs by binding excess endogenous aldehydes. Vitamin C can increase tissue cysteine and glutathione levels. The aim of the present study was to investigate whether a dietary supplementation of vitamin C can lower tissue aldehydes and blood pressure and normalize associated biochemical and histopathological changes in SHRs. Starting at 12 weeks of age, animals were divided into 3 groups of 6 animals each. Animals in the WKY-control group and SHR-control group were given a normal diet and the SHR-vitamin C group a diet supplemented with vitamin C (1000 mg/kg feed) for the next 9 weeks. After nine weeks, systolic blood pressure, platelet [Ca2+]i, plasma insulin and liver, kidney and aortic aldehyde conjugates were significantly higher in SHR controls as compared to WKY controls and the SHR-vitamin C group. SHR-controls also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin C supplementation in SHRs lowered the systolic blood pressure, tissue aldehyde conjugates and attenuated adverse renal vascular changes.

Dietary alpha-lipoic acid supplementation lowers blood pressure in spontaneously hypertensive rats.

BACKGROUND AND OBJECTIVES: In spontaneously hypertensive rats (SHRs), excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing cytosolic free calcium and blood pressure. The thiol compound, N-acetyl cysteine, normalizes elevated blood pressure in SHRs by binding excess endogenous aldehydes and normalizing membrane Ca2+ channels and cytosolic free calcium. The aim of the present study was to investigate whether a dietary supplementation of an endogenous fatty acid, alpha-lipoic acid, another thiol compound that is known to increase tissue cysteine and glutathione, can lower blood pressure and normalize associated biochemical and histopathological changes in SHRs. METHODS AND RESULTS: Starting at 12 weeks of age, animals were divided into three groups of six animals each. Animals in the Wistar- Kyoto (WKY) rat control group and the SHR control group were given a normal diet, and the SHR-lipoic acid group was given a diet supplemented with lipoic acid (500 mg/kg feed) for the next 9 weeks. After 9 weeks, systolic blood pressure, platelet [Ca2+]i, plasma insulin and liver, kidney and aortic aldehyde conjugates were significantly higher in SHR controls as compared with WKY rat controls and the SHR lipoic acid group. SHR controls also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. CONCLUSIONS: Dietary alpha-lipoic acid supplementation in SHRs lowered the systolic blood pressure, cytosolic [Ca2+]i, blood glucose and insulin levels, and tissue aldehyde conjugates, and attenuated adverse renal vascular changes.

Dietary lipoic acid supplementation prevents fructose-induced hypertension in rats.

BACKGROUND AND AIMS: In fructose-induced hypertension in Wistar-Kyoto (WKY) rats, excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, alter membrane Ca2+ channels and increase cytosolic free calcium and blood pressure. The thiol compound N-acetyl cysteine prevents such hypertension by binding these aldehydes and normalizing membrane Ca2+ channels and cytosolic free calcium. The aim of this work was to investigate whether dietary supplementation of an endogenous fatty acid, alpha-lipoic acid, another thiol compound known to increase cysteine and glutathione, prevents this hypertension and its associated biochemical and histopathological changes. METHODS AND RESULTS: Starting at seven weeks of age, animals were divided into three groups of six animals each and treated as follows: control (normal diet and normal drinking water); fructose (normal diet and 4% fructose in drinking water); fructose + lipoic acid (diet supplemented with lipoic acid 500 mg/kg feed and 4% fructose in drinking water). After 14 weeks, systolic blood pressure, platelet [Ca2+]i, plasma glucose and insulin and kidney and aortic aldehyde conjugates were significantly higher in the fructose group. These also displayed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. CONCLUSION: Dietary alpha-lipoic acid supplementation in fructose-treated WKY rats may prevent their increase in systolic blood pressure by normalizing cytosolic [Ca2+], blood glucose and insulin, kidney and aortic aldehyde conjugates and preventing adverse renal vascular changes.

Foregone health care among adolescents.

CONTEXT: No annual national population estimates exist of the numbers of adolescents who think they need but do not receive health care or their risk of health problems. OBJECTIVE: To describe the proportion of adolescents who report foregone health care each year and the influence of sociodemographic factors, insurance status, past health care, and health risks/behaviors on foregone care. DESIGN: Cross-sectional analyses of data from wave 1 of the National Longitudinal Study of Adolescent Health, conducted during 1995. SETTING: In-home interviews conducted throughout the United States. PARTICIPANTS: Of 27000 adolescents in grades 7 through 12 who were invited to participate, 20746 (76.8%) completed the in-home interview. MAIN OUTCOME MEASURE: Reported foregone health care in the preceding year by individual and family characteristics, insurance status, past health care, health/behavior risk factors, and symptoms. RESULTS: On average, 2268 (18.7%) of 12 079 adolescents reported foregone health care within the past year. Factors associated with decreased risk of foregone care included continuous private or public insurance (adjusted relative risk [95% confidence interval], 0.64 [0.50-0.82] to 0.82 [0.70-0.96]), and having a physical examination within the past year (0.87 [0.78-0.97] for male and 0.79 [0.70-0.88] for female adolescents). Factors associated with increased risk of foregone care included older age (1.12 [1.06-1.15] for male), minority race/ethnicity (1.25 [1.06-1.46] to 1.50 [1.30-1.73]), single-parent home (1.31 [1.18-1.46] for female), and disability (2.03 [1.61-2.52] for male and 1.66 [1.20-2.10] for female). Adolescents participating in the following behaviors were more likely to report foregone care than those who did not: daily cigarette use (26.0% vs 16.8%; 1.34 [1.16-1.55]), frequent alcohol use (30.3% vs 18.1%; 1.34 [1.11-1.62] for male), and sexual intercourse (25.1% vs 15.1%; 1.23 [1.09-1.39] for male and 1.39 [1.23-1.56] for female). From 32.4% to 38.2% of adolescents with symptoms suggesting health problems reported foregone care (1.61 [1.13-2.26] to 2.03 [1.81-2.28]). CONCLUSIONS: Our study suggests that adolescents who forego care are at increased risk of physical and mental health problems. Efforts to improve adolescent health through health care should address factors influencing foregone care.

Antihypertensive effect of low ethanol intake in spontaneously hypertensive rats.

Light to moderate drinking in humans lowers the risk of coronary heart disease and may lower blood pressure. We examined the effect of chronic low daily alcohol consumption on blood pressure, platelet cytosolic free calcium [Ca2+]i, tissue aldehyde conjugates and renal vascular changes in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). We also examined the effects of the same weekly amount of alcohol consumption over a one day period each week simulating weekend drinking in humans. Animals, age 7 weeks, were divided into six groups of six animals each and were treated as follows: WKY and SHR control, normal drinking water; WKY and SHR, 0.5% ethanol in drinking water; WKY and SHR, 3.5% ethanol in drinking water one day/week. After 14 weeks systolic blood pressure, platelet [Ca2+]i, liver, kidney and aortic aldehyde conjugates were significantly higher (p < 0.05) in untreated SHRs as compared to untreated WKYs. Daily 0.5% ethanol consumption in SHRs significantly (p < 0.05) attenuated these changes and also attenuated smooth muscle cell hyperplasia and narrowing of the lumen in small arteries and arterioles of the kidney. WKY rats treated with 0.5% ethanol had lower aldehyde conjugates without any significant effect on blood pressure and platelet [Ca2+]i as compared to WKY controls. Consumption of 3.5% ethanol one day/week did not affect blood pressure and associated changes in normotensive WKY rats or hypertensive SHRs as compared to their respective controls. These results suggest that chronic daily low ethanol intake lowers blood pressure in SHRs by lowering tissue aldehyde conjugates and cytosolic free calcium.

Dietary vitamin B6 supplementation attenuates hypertension in spontaneously hypertensive rats.

In spontaneously hypertensive rats (SHRs) excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels, increasing cytosolic free calcium and blood pressure. N-acetyl cysteine normalizes elevated blood pressure in SHRs by binding excess endogenous aldehydes. It is known that dietary vitamin B6 supplementation can increase the level of endogenous cysteine. Our objective was to investigate whether a dietary supplementation of vitamin B6 can prevent hypertension and associated changes in SHRs. Starting at 7 weeks of age, animals were divided into three groups of six animals each. Animals in WKY-control group and SHR-control group were given a normal vitamin B6 diet; and SHR-vitamin B6 group, a high vitamin B6 diet (20 times the recommended dietary intake; RDA) for the next 14 weeks. After 14 weeks, systolic blood pressure, platelet [Ca2+]i and liver, kidney and aortic aldehyde conjugates were significantly higher in SHR controls compared to WKY controls. These animals also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin B6 supplementation attenuated the increase in systolic blood pressure, tissue aldehyde conjugates and associated changes. These results further support the hypothesis that aldehydes are involved in increased systolic blood pressure in SHRs and suggest that vitamin B6 supplementation may be an effective antihypertensive.

Dietary vitamin B6 supplementation prevents ethanol-induced hypertension in rats.

BACKGROUND AND AIMS: All known pathways of ethanol metabolism result in the production of acetaldehyde, a highly reactive compound. Acetaldehyde has been shown to deplete vitamin B6 in chronic alcoholics. It also binds with sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing vascular cytosolic free calcium, peripheral vascular resistance and blood pressure. The aldehyde-binding thiol compound, N-acetyl cysteine, attenuates elevated blood pressure and associated adverse changes in ethanol-induced hypertensive rats. Vitamin B6 supplementation increases the level of endogenous cysteine. Aim of this work was thus to investigate whether a dietary supplementation of vitamin B6 can prevent ethanol-induced hypertension and associated changes in Wistar-Kyoto (WKY) rats. METHODS AND RESULTS: Starting at 7 weeks of age, WKY rats were divided into three groups of six animals each. The control group received a normal vitamin B6 diet (regular chow) and normal drinking water, the ethanol group, the same diet plus 1% ethanol in the drinking water, and the ethanol + vitamin B6 group a high vitamin B6 diet (20 times normal diet) and 1% ethanol in the drinking water. After 14 weeks, systolic blood pressure, platelet [Ca2+]i and kidney and aortic aldehyde conjugate levels were significantly higher in the ethanol group. These rats also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin B6 supplementation prevented these changes. CONCLUSIONS: Dietary vitamin B6 supplementation prevented ethanol-induced hypertension and associated changes in WKY rats by normalizing tissue aldehyde conjugate levels.

Role of aldehydes in fructose induced hypertension.

Aldehydes are formed in tissues of humans and animals as intermediates of glucose and fructose metabolism and due to lipid peroxidation. N-acetyl cysteine (NAC), an analogue of the dietary amino acid cysteine, binds aldehydes thus preventing their damaging effect on physiological proteins. We measured systolic blood pressure (SBP), platelet cytosolic free calcium [Ca2+]i and tissue aldehyde conjugates in fructose induced hypertensive Wistar-Kyoto (WKY) rats and examined the effect of NAC in the diet on these parameters. Animals age 7 weeks were divided into three groups of 6 animals each and were treated as follows: WKY-control (chow diet and normal drinking water); WKY-Fructose (chow diet and 4% fructose in drinking water); WKY-Fructose+NAC (1.5% NAC in chow diet and 4% fructose in drinking water). After 11 weeks, systolic blood pressure, platelet [Ca2+]i and kidney aldehyde conjugates were all significantly higher in fructose treated rats. NAC treatment prevented these changes. These results suggest that aldehydes may be the cause of fructose induced hypertension and elevated cytosolic free calcium.

Aldehyde induced hypertension in rats: prevention by N-acetyl cysteine.

Methylglyoxal, a highly reactive endogenous aldehyde is formed in the tissue of humans and animals as an intermediate of glucose and fructose metabolism. N-acetyl cysteine (NAC), an analogue of the dietary amino acid cysteine, binds aldehydes thus preventing their damaging effect on physiological proteins. We measured systolic blood pressure (SBP), platelet [Ca2+]i, circulating nitric oxide levels, tissue aldehyde conjugates and renal vascular changes in chronic methyglyoxal treated Wistar-Kyoto (WKY) rats and examined the effect of NAC in the diet on these parameters. Animals, age seven weeks, were divided into three groups of six animals each and were treated as follows: WKY-control (chow diet and normal drinking water); WKY-methylglyoxal (chow diet and methyglyoxal in drinking water); WKY-methyglyoxal + NAC (1.5% NAC in diet and methylglyoxal in drinking water) for the next 18 weeks. Methylgyoxal in drinking water was given at a concentration of 0.2% during weeks 0-5; 0.4%, weeks 6-10; and 0.8%, weeks 11-18. After 18 weeks systolic blood pressure, platelet [Ca2+]i and kidney aldehyde conjugates were significantly higher and serum nitric oxide levels lower in methylglyoxal treated rats. Methylglyoxal treated rats also showed smooth muscle cell hyperplasia in the small artery and arterioles of the kidney. N-acetyl cysteine, an aldehyde binding thiol compound, prevented these changes.

Influence of physician confidentiality assurances on adolescents' willingness to disclose information and seek future health care. A randomized controlled trial.

CONTEXT: Adolescents' concerns about privacy in clinical settings decrease their willingness to seek health care for sensitive problems and may inhibit their communication with physicians. OBJECTIVE: To investigate the influence of physicians' assurances of confidentiality on adolescents' willingness to disclose information and seek future health care. DESIGN: Randomized controlled trial. SETTING: Three suburban public high schools in California. PARTICIPANTS: The 562 participating adolescents represented 92% of students in mandatory classes. INTERVENTION: After random assignment to 1 of 3 groups, the adolescents listened to a standardized audiotape depiction of an office visit during which they heard a physician who assured unconditional confidentiality, a physician who assured conditional confidentiality, or a physician who did not mention confidentiality. MAIN OUTCOME MEASURES: Adolescents' willingness to disclose general information, willingness to disclose information about sensitive topics, intended honesty, and likelihood of return visits to the physician depicted in the scenario were assessed by anonymous written questionnaire. RESULTS: Assurances of confidentiality increased the number of adolescents willing to disclose sensitive information about sexuality, substance use, and mental health from 39% (68/175) to 46.5% (178/383) (beta=.10, P=.02) and increased the number willing to seek future health care from 53% (93/175) to 67% (259/386) (beta=.17, P<.001). When comparing the unconditional with the conditional groups, assurances of unconditional confidentiality increased the number of adolescents willing to return for a future visit by 10 percentage points, from 62% (122/196) to 72% (137/190) (beta=.14, P=.001). CONCLUSIONS: Adolescents are more willing to communicate with and seek health care from physicians who assure confidentiality. Further investigation is needed to identify a confidentiality assurance statement that explains the legal and ethical limitations of confidentiality without decreasing adolescents' likelihood of seeking future health care for routine and nonreportable sensitive health concerns.