Proteome and secretome profiling of zinc availability in Cryptococcus neoformans identifies Wos2 as a subtle influencer of fungal virulence determinants.

BACKGROUND: Fungal infections impact over 25% of the global population. For the opportunistic fungal pathogen, Cryptococcus neoformans, infection leads to cryptococcosis. In the presence of the host, disease is enabled by elaboration of sophisticated virulence determinants, including polysaccharide capsule, melanin, thermotolerance, and extracellular enzymes. Conversely, the host protects itself from fungal invasion by regulating and sequestering transition metals (e.g., iron, zinc, copper) important for microbial growth and survival. RESULTS: Here, we explore the intricate relationship between zinc availability and fungal virulence via mass spectrometry-based quantitative proteomics. We observe a core proteome along with a distinct zinc-regulated protein-level signature demonstrating a shift away from transport and ion binding under zinc-replete conditions towards transcription and metal acquisition under zinc-limited conditions. In addition, we revealed a novel connection among zinc availability, thermotolerance, as well as capsule and melanin production through the detection of a Wos2 ortholog in the secretome under replete conditions. CONCLUSIONS: Overall, we provide new biological insight into cellular remodeling at the protein level of C. neoformans under regulated zinc conditions and uncover a novel connection between zinc homeostasis and fungal virulence determinants.

The plant natural product 2-methoxy-1,4-naphthoquinone stimulates therapeutic neural repair properties of olfactory ensheathing cells.

Olfactory ensheathing cells (OECs) are crucial for promoting the regeneration of the primary olfactory nervous system that occurs throughout life. Transplantation of OECs has emerged as a promising therapy for nervous system injuries, in particular for spinal cord injury repair. Functional outcomes in both animals and humans are, however, highly variable, primarily because it is difficult to rapidly obtain enough OECs for transplantation. Compounds which can stimulate OEC proliferation without changing the phenotype of the cells are therefore highly sought after. Additionally, compounds which can stimulate favourable cell behaviours such as migration and phagocytic activity are desirable. We conducted a medium-throughput screen testing the Davis open access natural product-based library (472 compounds) and subsequently identified the known plant natural product 2-methoxy-1,4-naphthoquinone as a stimulant of OEC viability. We showed that 2-methoxy-1,4-naphthoquinone: (i) strongly stimulates proliferation over several weeks in culture whilst maintaining the OEC phenotype; (ii) stimulates the phagocytic activity of OECs, and (iii) modulates the cell cycle. We also identified the transcription factor Nrf2 as the compound's potential molecular target. From these extensive investigations we conclude that 2-methoxy-1,4-naphthoquinone may enhance the therapeutic potential of OECs by stimulating proliferation prior to transplantation.

Supraspinal stimulation for treatment of refractory pain.

Refractory pain syndromes often have far reaching effects and are quite a challenge for primary care providers and specialists alike to treat. With the help of site-specific neuromodulation and appropriate patient selection these difficult to treat pain syndromes may be managed. In this article, we focus on supraspinal stimulation (SSS) for treatment of intractable pain and discuss off-label uses of deep brain stimulation (DBS) and motor cortex stimulation (MCS) in context to emerging indications in neuromodulation. Consideration for neuromodulatory treatment begins with rigorous patient selection based on exhaustive conservative management, elimination of secondary gains, and a proper psychology evaluation. Trial stimulation prior to DBS is nearly always performed while trial stimulation prior to MCS surgery is symptom dependent. Overall, a review of the literature demonstrates that DBS should be considered for refractory conditions including nociceptive/neuropathic pain, phantom limb pain, and chronic cluster headache (CCH). MCS should be considered primarily for trigeminal neuropathic pain (TNP) and central pain. DBS outcome studies for post-stroke pain as well as MCS studies for complex regional pain syndrome (CRPS) show more modest results and are also discussed in detail.

Skin innervation at different depths correlates with small fibre function but not with pain in neuropathic pain patients.

BACKGROUND: Neuropathy can lead not only to impaired function but also to sensory sensitization. We aimed to link reduced skin nerve fibre density in different levels to layer-specific functional impairment in neuropathic pain patients and tried to identify pain-specific functional and structural markers. METHODS: In 12 healthy controls and 36 patients with neuropathic pain, we assessed clinical characteristics, thermal thresholds (quantitative sensory testing) and electrically induced pain and axon reflex erythema. At the most painful sites and at intra-individual control sites, skin biopsies were taken and innervation densities in the different skin layers were assessed. Moreover, neuronal calcitonin gene-related peptide staining was quantified. RESULTS: Perception of warm, cold and heat pain and nerve fibre density were reduced in the painful areas compared with the control sites and with healthy controls. Warm and cold detection thresholds correlated best with epidermal innervation density, whereas heat and cold pain thresholds and axon reflex flare correlated best with dermal innervation density. Clinical pain ratings correlated only with epidermal nerve fibre density (r = 0.38, p < 0.05) and better preserved cold detection thresholds (r = 0.39, p < 0.05), but not with other assessed functional and structural parameters. CONCLUSIONS: Thermal thresholds, axon reflex measurements and assessment of skin innervation density are valuable tools to characterize and quantify peripheral neuropathy and link neuronal function to different layers of the skin. The severity of small fibre neuropathy, however, did not correspond to clinical pain intensity and a specific parameter or pattern that would predict pain intensity in peripheral neuropathy could not be identified.

Outcomes in verteporfin photodynamic therapy for choroidal neovascularisation--'beyond the TAP study'.

AIMS: To report on the clinical efficacy of verteporfin photodynamic therapy (PDT) in the treatment of choroidal neovascularisation (CNV) in an NHS setting and to compare treatment rates and outcomes with those in the published literature. PATIENTS AND METHODS: Patients with a visual acuity of 6/60 or better Snellen equivalent and predominantly classic or classic/no occult CNV within 200 microm of the centre of the fovea were enrolled and followed for a minimum of 12 months. Assessment at baseline and all follow-up visits comprised refraction protocol logMAR visual acuity, contrast sensitivity, and stereoscopic fluorescein angiography. RESULTS: A total of 170 eyes of 159 patients were enrolled with CNV due to: 147 age-related macular degeneration (AMD) (90 classic/no occult, 21 recurrent after confluent laser, 36 predominantly classic with occult), 10 pathological myopia, and 13 others. Response to treatment (loss of < 15 letters) at 12 months was 73% overall, 76% in AMD, 70% in classic/no occult, and 89% in predominantly classic. The mean number of treatments in the first year was 2.7. Contrast sensitivity was unchanged. CONCLUSIONS: Verteporfin PDT delivered in a NHS setting can be at least as effective as and requires fewer treatments than reported in the literature.

Quality of life in cystic fibrosis: the impact of gender, general health perceptions and disease severity.

BACKGROUND: Disease progression in cystic fibrosis (CF) is marked by deterioration across a number of physiological systems. In addition, there is evidence that females have a worse prognosis than males. The current work assesses the impact of both these factors on health related quality of life (HRQoL). METHODS: Two hundred and twenty-three adolescents and adults completed the cystic fibrosis quality of life (CFQoL) questionnaire with a further 185 approached and not responding by non-completion of the questionnaire. The CFQoL is divided into nine domains: physical, social, treatment, chest symptoms, emotional functioning, concerns for the future, relationships, body image, and career. Measurement of objective clinical status included, body mass index (BMI), and percentage of predicted forced expiratory volume in one second (FEV1). General health perceptions (GHP) were also measured. RESULTS: Patients were sub-divided by gender and disease severity (mild > 70% FEV1, moderate 40-69% and severe < 40%). Factorial analysis of variance indicated significant main effects for FEV1 (F = 587.98, P < or = 0.001) and BMI (F = 17.29, P < or = 0.001) as a function of disease severity. Post hoc tests revealed significant two-group differences for FEV1 and BMI between disease severity groups. No differences were observed for gender across FEV1 or BMI. Differences emerged across most CFQoL domains for disease severity, with the exception of concerns for the future, which was consistently low throughout. Gender differences emerged for chest symptoms, emotional functioning, concerns for the future, body image and career. With the exception of body image, females exhibited poorer HRQoL. Pearson correlations indicated that females' perception of health was more closely related to clinical status than males. CONCLUSIONS: Disease severity has an impact on HRQoL in adolescents and adults with CF. Some differences emerged between males and females, with females generally reporting poorer HRQoL. Evidence indicated that males and females perceived their health status differently, with females having a more accurate perception of objective clinical health status.

Validation of the SF-36 for the assessment of quality of life in adolescents and adults with cystic fibrosis.

BACKGROUND: Generic health-related quality of life measures are often applied to disease groups without assessment of their psychometric properties. The current work assesses the properties of the Short Form 36-item (SF-36) questionnaire in a British sample of adolescents and adults with cystic fibrosis (CF). METHODS: Two hundred and twenty-three adolescents and adults with CF completed the SF-36 with a further 185 approached and not responding by non-completion of the questionnaire. The structure and internal reliability of the instrument was assessed by principal components analysis, Cronbach alpha coefficients and item to domain correlations. Differences between disease severity groups were assessed by analysis of variance. RESULTS: Factor analysis of the SF-36 scores broadly confirmed domain structures for the SF-36. Cronbach alpha coefficients were high (range 0.82-0.91) and item-to-same domain correlations were stronger than item-to-unrelated domain correlations. Examination of differences between mild, moderate and severe disease states revealed four significant main effects for: physical functioning, role limitation due to physical functioning, general health perceptions and energy and vitality. The analysis also revealed the presence of numerous ceiling effects across domains. CONCLUSIONS: The domain structure of the SF-36 was demonstrated to be robust. However, the discriminatory ability of the measure was disappointing. The presence of ceiling effects and the low frequency of differences between intermediate disease severity groups indicated that the SF-36 was not discriminatory with respect to mild disease states or progression of illness.

Trends in HIV seroprevalence and risk among gay and bisexual men who inject drugs in San Francisco, 1988 to 2000.

OBJECTIVES: To determine trends in HIV infection and risk behaviors among street-recruited self-identified gay and bisexual male injection drug users (IDUs) in San Francisco. METHODS: Trends in HIV infection and risk behaviors were calculated for gay/bisexual ( n = 1594 interviews) IDUs in 26 semiannual cross sections from 1988 to 2000. RESULTS: HIV seroprevalence among gay/bisexual IDUs decreased from the range of 35% to 45% in 1988/1989 to 25% in 1996 and then began to increase, reaching 42% in 2000. In contrast, HIV prevalence among heterosexual male IDUs remained stable during the study period. For gay/bisexual IDUs, injection and sex-related HIV risk behaviors declined modestly throughout the study period. As of the last cross section (July 2000), however, over a third of respondents reported recent syringe sharing or unprotected anal sex. CONCLUSIONS: Gay/bisexual men who inject drugs continue to be at elevated risk for HIV, suggesting that interventions such as amphetamine drug treatment and sexual risk reduction programs targeted at this population are needed.

Predictors and prevention of nonfatal overdose among street-recruited injection heroin users in the San Francisco Bay Area, 1998-1999.

OBJECTIVES: This study sought to determine prevalence of and risk factors for nonfatal recent overdose among street-recruited injection heroin users. METHODS: From August 1998 through July 1999, 1427 heroin injectors were recruited from 6 inner-city neighborhoods in the San Francisco Bay Area, Calif, and interviewed. Factors hypothesized to be associated with recent overdose were analyzed with logistic regression. RESULTS: Of the 1427 participants, 684 (48%) had had an overdose, 466 (33%) had experienced 2 or more overdose events, and 182 (13%) had had a recent overdose. In multiple logistic regression, being younger (adjusted odds ratio [OR] for each year of increasing age = 0.95; 95% confidence interval [CI] = 0.94, 0.97), having been arrested 3 or more times in the past year (adjusted OR = 2.50; 95% CI = 1.61, 3.87), drinking 4 or more alcoholic drinks per day (adjusted OR = 2.05; 95% CI = 1.37, 3.05), and having participated in methadone detoxification during the past year (adjusted OR = 1.47; 95% CI = 1.03, 2.09) were independently associated with recent overdose. Being homeless; identifying as gay, lesbian, bisexual, or transgender; having spent 5 or more years in prison or jail; and having engaged in sex work also were associated with recent overdose. CONCLUSIONS: Targeted interventions that decrease risk for overdose are urgently needed.

Sexual transmission of HIV-1 among injection drug users in San Francisco, USA: risk-factor analysis.

BACKGROUND: Many new HIV-1 infections in the USA occur in injection drug users (IDUs). HIV-1seroconversion of IDUs is mainly associated with injection-related risk factors. Harm- reduction programmes concentrate on injection-risk behaviour. We aimed to establish whether injection or sexual risk factors, or both, were associated with HIV-1antibody seroconversion of street-recruited IDUs in San Francisco, from 1986 to 1998. METHODS: IDUs were enrolled every 6 months from four community sites. We did a nested case-control study comparing 58 respondents who seroconverted between visits with 1134 controls who remained seronegative. Controls were matched with cases by sex and date. Adjusted odds ratios and 95% CI were calculated for men and women by use of conditional logistic regression. FINDINGS: Men who had sex with men were 8.8 times as likely to seroconvert (95% CI 3.7-20.5) as heterosexual men. Women who reported having traded sex for money in the past year were 5.1 times as likely as others to seroconvert (95% CI 1.9-13.7). Women younger than 40 years were more likely to seroconvert than those 40 years or older (2.8 [1.05-7.6]), and women who reported having a steady sex-partner who injected drugs were less likely to seroconvert than other women (0.32 [0.11-0.92]). INTERPRETATION: HIV-1 seroconversion of street-recruited IDUs in San Francisco is strongly associated with sexual behaviour. HIV-1risk might be reduced by incorporation of innovative sexual-risk-reduction strategies into harm-reduction programmes.

IFN-beta1a may increase serum levels of TIMP-1 in patients with relapsing-remitting multiple sclerosis.

Serum levels of matrix metalloprotease-9 (MMP-9) and tissue inhibitor of MMP-1 (TIMP-1) were measured monthly in 7 patients with relapsing-remitting multiple sclerosis (MS) 6 months before and 6 months during treatment with weekly intramuscular (i.m.) injections of interferon-beta1a (IFN-beta1a) 30 microg. Within-patient median MMP-9 levels were unchanged on treatment. Within-patient median TIMP-1 levels were higher during months 1-6 (771.5 ng/ml) and during months 4, 5, and 6 of treatment (793 ng/ml) compared with 6 months pretreatment (414 ng/ml) (respectively, p = 0.10, p = 0.047; Wilcoxon signed-rank test). These preliminary data suggest that IFN-beta1a therapy may increase TIMP-1 levels.

Ways of coping with cystic fibrosis: implications for treatment adherence.

PURPOSE: How individuals cope with aspects of cystic fibrosis (CF) has the potential to influence their self management and the course of their disease. To evaluate how individuals cope with CF, a disease specific coping scale was developed and validated. A second objective of the work was to examine the relationship between coping styles and treatment adherence. METHODS: The development of the coping scale constituted a longitudinal design. A cross-sectional questionnaire design was used to examine the coping-adherence relationship. The development and validation of the coping scale comprised three phases: (1) Initially, 60 patients were interviewed to identify CF concerns. From this information a list of 23 concerns were recorded; (2) Eighty-three patients were interviewed to identify CF coping responses. For each concern, they were asked what they did or thought to ease the worry. A list of 24 coping strategies were recorded that formed a comprehensive set of items as to how people with CF act, feel and think about aspects of their disease; and (3) Further development and testing of the questionnaire involved 174 patients completing the measure. Four distinct ways of coping with CF were identified by factor analysis. These were termed optimistic acceptance, hopefulness, distraction and avoidance. The cronbach alpha coefficients were 0.74 (optimistic acceptance), 0.69 (hopefulness). 0.71 (distraction) and 0.76 (avoidance). To evaluate the relationship between coping and treatment adherence 60 patients completed the CF Coping Questionnaire and the Manchester Adult Cystic Fibrosis Compliance Questionnaire. RESULTS: Compared with patients who were non-adherent, those who were adherent scored higher on the optimistic acceptance scale (physiotherapy p < 0.05, enzymes p < 0.003, vitamins p < 0.05) and hopefulness scale (physiotherapy p < 0.002, enzymes p < 0.001). Those who were partially adherent reported using distraction as a way of coping to a greater extent than adherent or non-adherent patients (all p's < 0.05). Non-adherent patients used avoidance strategies to a greater extent than those who were adherent (physiotherapy p < 0.05, enzymes p < 0.04), although interestingly, adherence with exercise was associated with avoidant coping (p < 0.004). CONCLUSIONS: The degree of adherence to treatments was influenced by a person's style of coping. The identification of effective coping strategies to aid both long-term psychological and clinical well-being should improve the management of non-adherence.

Relationship between serum levels of IL-10, MRI activity and interferon beta-1a therapy in patients with relapsing remitting MS.

BACKGROUND: The purposes of this study were to: (1) compare monthly serum IL-10 in patients with relapsing remitting (RR) multiple sclerosis (MS) and healthy controls, (2) determine the relationship between IL-10 and MRI activity and (3) determine the effect of interferon beta-1a (IFNB-1a) treatment on IL-10 levels. RESULTS: Median serum IL-10 levels were lower in untreated RRMS (185.5 pg/ml) compared to controls (438.5 pg/ml) (P=0.19). Serum levels of IL-10 did not appear to predict the appearance of new gadolinium-enhancing (Gd+) lesions concurrently or 1 month thereafter. However, IL-10 levels were more likely to be elevated the month during which Gd+ lesions resolved (OR=3.14, P=0.01). Median IL-10 levels were lower during IFNB-1a treatment (P=0.01). CONCLUSIONS: These observations suggest a relationship between serum IL-10 levels and resolution of abnormal vascular permeability in new lesions.

Cross cultural differences in health related quality of life in adolescents with cystic fibrosis.

PURPOSE: Quality of Life (QoL) is an important outcome measure in health care and pharmacological trials. The trend towards multinational clinical trials may be problematic because it is unclear as to whether, or to what extent, QoL-measures are comparable across cultures. This study compared QoL between English and German adolescents with Cystic Fibrosis (CF) and their healthy peers. METHOD: The study comprised a cross-sectional design. The English subjects formed two groups; 58 adolescents with CF and 49 healthy controls. The German subjects consisted of 26 adolescents with CF and 75 healthy controls. Quality of life was measured using the English and German versions of the SF-36. Demographic (age and gender) and clinical data (FEV1% predicted and BMI) were also recorded. RESULTS: The English and German CF groups had similar age-adjusted lung function and body mass index. Both the English CF and control groups reported a poorer quality of life than their respective German counterparts across several domains of the SF-36. These were limitations in activities due to physical health problems and emotional difficulties, social functioning, energy and vitality and pain. CONCLUSIONS: The differences in quality of life between English and German adolescents with CF appear to be either culturally determined or due to idiosyncrasies in the translations of the SF-36. rather than a consequence of their disease or its management.

Development of a disease specific health related quality of life measure for adults and adolescents with cystic fibrosis.

BACKGROUND: Health related quality of life (HRQoL) measurement is important in determining the impact of disease on daily functioning and subsequently informing interventions. In cystic fibrosis (CF) generic HRQoL measures have been employed but these may not be sufficiently specific. The aim of the current work was to develop and validate a disease specific HRQoL measure for adults and adolescents with cystic fibrosis. METHODS: Areas of concern to adults and adolescents with CF were identified by unstructured interviews, self-administered questionnaires, consultation with multidisciplinary specialist staff, a review of the relevant literature, and examination of other HRQoL measures. Items for the questionnaire were generated on the basis of this process. Continued evaluation and development of the Cystic Fibrosis Quality of Life (CFQoL) questionnaire was undertaken by a process of statistical analysis and continued feedback from patients. The full testing and validation of the CFQoL questionnaire took place over four phases: (1) initial item generation and testing of a preliminary questionnaire, (2) testing and validation of the second version of the questionnaire, (3) test-retest reliability of a third and final version of the questionnaire, and (4) sensitivity testing of the final version of the questionnaire. RESULTS: Nine domains of functioning were identified using principal components analysis with varimax rotation. Internal reliability of the identified domains was demonstrated using Cronbach alpha coefficients (range 0.72-0.92) and item to total domain score correlations. Concurrent validity (range r = 0.64-0.74), discriminatory ability between different levels of disease severity, sensitivity across transient changes in health (effect size range, moderate d = 0.56 to large d = 1.95), and test-retest reliability (r = 0.74-0.96) were also found to be robust. CONCLUSIONS: The CFQoL questionnaire is a fully validated disease specific measure consisting of 52 items across nine domains of functioning which have been identified by, and are of importance to, adolescents and adults with cystic fibrosis. This measure will be useful in clinical trials and longitudinal studies.

HyAlx, an aristaless-related gene, is involved in tentacle formation in hydra.

Developmental gradients are known to play important roles in axial patterning in hydra. Current efforts are directed toward elucidating the molecular basis of these gradients. We report the isolation and characterization of HyAlx, an aristaless-related gene in hydra. The expression patterns of the gene in adult hydra, as well as during bud formation, head regeneration and the formation of ectopic head structures along the body column, indicate the gene plays a role in the specification of tissue for tentacle formation. The use of RNAi provides more direct evidence for this conclusion. The different patterns of HyAlx expression during head regeneration and bud formation also provide support for a recent version of a reaction-diffusion model for axial patterning in hydra.

Living arrangements affect dietary quality for U.S. adults aged 50 years and older: NHANES III 1988-1994.

The number and proportion of older U.S. adults who live alone have increased dramatically in the past three decades, and there is concern that these individuals may have particularly poor dietary quality. We examined the association of four living arrangements (living with a spouse only, with a spouse plus someone else, with someone other than a spouse or living alone) with dietary quality (the number of low nutrients out of a possible 15, with low defined as <67% of the recommended dietary allowance) among 6525 U.S. adults aged 50-64 y and those >/=65 y in the third National Health and Nutrition Examination Survey (NHANES III 1988-1994). Among non-Hispanic Caucasian adults, those who lived with a spouse only had better dietary quality, with significant differences ranging from 0.8 to 1.5 fewer low nutrients compared with those with other living arrangements. Effects of living arrangements on dietary quality were also seen among non-Hispanic African-Americans, Mexican-Americans, and those of "other" races, but differences were significant only for African-American men aged >65 y living with a spouse plus others (1.6 additional low nutrients compared with those living with a spouse only). Energy intake was strongly associated with dietary quality, but did not account for the associations between living arrangements and dietary quality. Although middle-aged and older adults with living arrangements other than living with a spouse only (including those living alone) tended to have poorer dietary quality, the effects varied substantially across age, gender and ethnic categories.

Lack of association of C-reactive protein and coronary calcium by electron beam computed tomography in postmenopausal women: implications for coronary artery disease screening.

OBJECTIVES: We sought to test the hypothesis that C-reactive protein, a marker of inflammation, would correlate positively with coronary calcium, a marker of atherosclerosis, in postmenopausal women. BACKGROUND: High sensitivity testing for C-reactive protein (hsCRP) has recently been shown in large population studies to predict cardiac events in asymptomatic postmenopausal women. Coronary calcification determined by electron beam computerized tomography (EBCT) has also been suggested to be predictive of cardiac events in women. METHODS: We performed hsCRP testing and determined calcium scores by EBCT in 172 asymptomatic postmenopausal women (mean age: 64.5 +/- 7.9 years) at risk for cardiac disease. Risk factors were determined by history, physical, electrocardiogram, exercise testing, and lipoprotein profiles. RESULTS: Calcium scores ranged from 0 to 2,618. For analysis, calcium scores were divided into three groups; none (0 to 10), minimal (>10 to 50), and significant (>50). Overall, there was no significant positive relationship between hsCRP level and calcium score. Specifically, the hsCRP levels (mg/dl) were 0.24 +/- 0.43, 0.33 +/- 0.47 and 0.17 +/- 0.32 (medians 0.11, 0.15, and 0.06) for women with none, minimal, and significant coronary calcification, respectively. In subgroup analysis, a similar lack of positive association was observed after stratification by smoking status and by hormone replacement therapy use, two factors known to increase hsCRP. CONCLUSIONS: In contrast to our a priori hypothesis, we found no evidence of a positive association between hsCRP and calcium score by EBCT. These data thus raise the possibility that hsCRP and EBCT calcium score reflect different pathologic processes, an issue with implications for coronary artery disease screening.

The effect of syringe exchange use on high-risk injection drug users: a cohort study.

OBJECTIVE: To determine whether syringe exchange program use is associated with cessation of syringe sharing among high-risk injection drug users. DESIGN AND METHODS: Between 1992 and 1996, street-recruited injection drug users were interviewed and received HIV testing and counseling semi-annually, as part of a dynamic cohort study. We examined a cohort of 340 high-risk injection drug users for whom two observations, 6-months apart, were available and who reported syringe sharing at the first interview. Multivariate logistic regression analysis was performed to determine the relationship between syringe exchange program use and cessation of syringe sharing, while controlling for confounding factors. RESULTS: At follow-up interview, 60% (204 of 340) reported quitting syringe sharing. High-risk injection drug users who began using the syringe exchange program were more likely to quit sharing syringes [adjusted odds ratio (AOR), 2.68; 95% confidence interval (CI), 1.35-5.33], as were those who continued using the syringe exchange program (AOR,1.98; 95% CI, 1.05-3.75) in comparison with non-syringe exchange program users, while controlling for confounding factors. CONCLUSIONS: The initiation and continuation of syringe exchange program use among high-risk injection drug users is independently associated with cessation of syringe sharing. Syringe exchange program use can be an important component in reducing the spread of blood-borne infectious diseases among high-risk injection drug users.