Herpes simplex virus type 2 shedding in human immunodeficiency virus-negative men who have sex with men: frequency, patterns, and risk factors.

We investigated the frequency, site, and risk factors for herpes simplex virus (HSV) shedding in 30 human immunodeficiency virus (HIV)-negative HSV type 2 (HSV-2)-seropositive men who have sex with men. Subjects collected daily HSV culture samples from genital, perianal, and oral areas for 100 days and maintained diaries of signs and symptoms. Sixteen men (53.3%) shed HSV-2, and 9 (56.3%) of 16 men who were also HSV type 1 (HSV-1)-seropositive shed HSV-1. Overall, HSV-2 was isolated on 3.1% of the days; 68% of the isolations were on days that lesions did not occur. HSV-2 shedding was predominantly perianal (83.3%). HSV-1 was isolated on 2.1% of the days; 23 of 24 HSV-1 isolates were from oral areas. Rates of perianal or genital shedding were 6.6% on the days that participants reported prodromal symptoms and 1.9% on the days that participants did not report prodromal symptoms (P<.001). Men seropositive for both HSV-1 and HSV-2 were significantly more likely to shed HSV-2 (odds ratio, 4.1; 95% confidence interval, 1.4-11.9) than were HSV-2-seropositive men. HSV-2-seropositive men who have sex with men have frequent subclinical HSV-2 shedding, usually from the perianal area, and more frequent prodromal HSV-2 shedding.

Safety and toxicity of nonoxynol-9 gel as a rectal microbicide.

BACKGROUND AND OBJECTIVES: Methods of HIV and STD prevention, which can be controlled by the receptive partner, are a high priority for research and development. Studies on the safety of Nonoxynol-9 (N-9) on the vaginal mucosa have yielded conflicting results. No Phase I study has evaluated the effect of N-9 on the rectal mucosa. GOALS: To assess the safety of 52.5 mg of N-9 in a 1.5-g gel when applied one to four applicators per day to the rectum and penis. STUDY DESIGN: The study included 25 HIV-negative and 10 HIV-positive, monogamous gay male couples in which each partner was exclusively insertive or receptive while using N-9 gel. Each participant served as his own control during placebo gel use compared to during N-9 gel use. Receptive partners underwent anoscopic examination after 1 week of placebo use and after 2, 5, and 6 weeks of N-9 gel use, with rectal biopsies obtained after 1 week of placebo use and after 5 and 6 weeks of N-9 gel use. Insertive partners had safety monitoring after 1 week of placebo use and after 2, 5, and 6 weeks of N-9. RESULTS: No rectal ulcers were detected; superficial rectal erosions were noted in two HIV-negative participants. Abnormal or slightly abnormal histologic abnormalities of rectal biopsies were detected in 31 (89%) receptive participants after N-9 gel use compared to 24 (69%) participants after 1 week of placebo gel use. Meatal ulceration, not caused by herpes simplex virus, was detected in one HIV-negative participant. CONCLUSION: Low-dose N-9 gel was not associated with macroscopic rectal and penile epithelial disruption or inflammation, but histologic abnormalities were commonly observed during N-9 gel as well as during placebo gel use.

Substance use and psychological adjustment in homeless adolescents: a test of three models.

Three models of adolescent substance use, the deviance-prone, affect-regulation, and normative development models, were assessed regarding their ability to predict the substance use of a high-risk homeless adolescent sample with high rates of deviance, depression, and substance use. Hierarchical multiple regression analyses that included tests for curvilinear and gender interaction effects were performed. Results supported the deviance-prone model most strongly, with delinquency but not aggressive behavior predicting substance use. The affect-regulation model received support for females but not for males. With respect to the normative development model, results did not indicate that moderate substance users were better off than abstainers in terms of negative affect or interpersonal relationships.

Activation of the 2'-N-acetyltransferase gene [aac(2')-Ia] in Providencia stuartii by an interaction of AarP with the promoter region.

The aac(2')-Ia gene in Providencia stuartii encodes a 2'-N-acetyltransferase capable of acetylating both peptidoglycan and certain aminoglycoside antibiotics. Regulation of the aac(2')-Ia gene is influenced in a positive manner by the product of the aarP gene, which encodes a small transcriptional activator of the AraC (XylS) family. In this study, we demonstrate the sequence requirements at the aac(2')-Ia promoter for AarP binding and activation.

Incidence of HIV and sexually transmitted diseases (STD) in a cohort of HIV-negative men who have sex with men (MSM).

OBJECTIVE: To determine the prevalence of sexually transmitted diseases (STD) and incidence of and risk factors for STD, including HIV-1, among a cohort of HIV-negative men who have sex with men (MSM). SETTING: Seattle, Washington, United States. PARTICIPANTS: Prospective cohort of 578 HIV-negative MSM in which risk factors for acquiring a STD over 12 months follow-up were evaluated using a cumulative incidence analysis. MAIN OUTCOME MEASURES: Baseline tests obtained were: herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) Western blots, hepatitis B, and syphilis serologies; anorectal and pharyngeal Neisseria gonorrhoeae (GC) cultures; first-catch urine for leukocyte esterase (LE) and Chlamydia trachomatis (CT) ligase chain reaction (LCR). Men with a positive urine LE had urethral GC cultures obtained. The following outcomes were measured over 12 months follow-up: incident symptomatic bacterial STD (urethritis, proctitis, epididymitis), HSV-1 and HSV-2 seroconversion, and HIV-1 seroconversion. The 31 incident cases of STD (men with bacterial STD) were compared with those 489 men without symptomatic bacterial STD or seroconversion to HSV-1, HSV-2 or HIV-1 infection. RESULTS: Bacterial STD were found in nine participants at enrollment; there were two cases of nonchlamydial urethritis, two cases of nonchlamydial epididymitis, and five cases of asymptomatic GC infection. At enrollment, HSV-2 antibodies were detected in 149 (26.0%) of 572 men and prior hepatitis B infection in 145 (34.8%) of 417 unvaccinated men. During the 1-year of follow-up, 31 men (5.7/100 person-years) had 34 episodes of a symptomatic bacterial STD syndrome (urethritis, epididymitis or proctitis). Urethritis was the most common STD syndrome, detected in 29 men, of whom 10 had GC and 19 had nongonococcal urethritis. In the 1-year of follow-up, five participants seroconverted to HIV-1 (1.3/100 person-years), four to HSV-2 (1.0/100 person-years), and seven to HSV-1 (4.3/100 person-years). Unprotected insertive anal sex [odds ratio (OR) 2.6; 95% confidence interval (CI) 1.2-5.6]; and nitrite inhalant ('poppers') use (OR, 2.3; 95% CI, 1.0-5.0) were independently associated with incident STD. CONCLUSIONS: STD and HIV infection continue to be acquired even in a city with an overall low bacterial STD prevalence and among educated MSM receiving regular HIV screening and risk-reduction. Urethritis was the most common STD detected, and public health messages aimed at MSM need to emphasize safe insertive as well as receptive sexual practices.

Herpes simplex virus shedding among human immunodeficiency virus-negative men who have sex with men: site and frequency of shedding.

The frequency and anatomic location of subclinical and symptomatic herpes simplex virus (HSV) shedding were evaluated among human immunodeficiency virus (HIV)-negative HSV-2-seropositive men who have sex with men (MSM). Eight men attended a research clinic daily for 30 days for a detailed genital examination and anoscopy with colposcopy to detect herpes lesions. HSV cultures were obtained daily from four sites (perianal, urethral, penile shaft, and oral) at home and the research clinic. Signs and symptoms of genital herpes were recorded by the participants and clinician. Three (37.5%) of the men shed HSV. Overall, the 8 men shed HSV on 5.5% of days cultures were obtained and shed subclinically on 2.7% of days. All HSV shedding was perianal or rectal; only 1 symptomatic recurrence, concurrent with an external perianal lesion, was detected by anoscopy. Subclinical HSV shedding was frequent among HIV-negative MSM, and anoscopy with colposcopy did not increase the detection rate of rectal HSV lesions or shedding.

A regulatory cascade involving AarG, a putative sensor kinase, controls the expression of the 2'-N-acetyltransferase and an intrinsic multiple antibiotic resistance (Mar) response in Providencia stuartii.

A recessive mutation, aarG1, has been identified that resulted in an 18-fold increase in the expression of beta-galactosidase from an aac(2')-lacZ fusion. Transcriptional fusions and Northern blot analysis demonstrated that the aarG1 allele also resulted in a large increase in the expression of aarP, a gene encoding a transcriptional activator of aac(2')-Ia. The effects of aarG1 on aac(2')-Ia expression were mediated by aarP-dependent and -independent mechanisms. The aarG1 allele also resulted in a multiple antibiotic resistance (Mar) phenotype, which included increased chloramphenicol, tetracycline and fluoroquinolone resistance. This Mar phenotype also resulted from aarP-dependent and -independent mechanisms. Sequence analysis of the aarG locus revealed the presence of two open reading frames, designated aarR and aarG, organized in tandem. The putative AarR protein displayed 75% amino acid identity to the response regulator PhoP, and the AarG protein displayed 57% amino acid identity to the sensor kinase PhoQ. The aarG1 mutation, a C to T substitution, resulted in a threonine to isoleucine substitution at position 279 (T279I) in the putative sensor kinase. The AarG product was functionally similar to PhoQ, as it was able to restore wild-type levels of maganin resistance to a Salmonella typhimurium phoQ mutant. However, expression of the aarP and aac(2')-Ia genes was not significantly affected by the levels of Mg2+ or Ca2+, suggesting that aarG senses a signal other than divalent cations.

Mutations in aarE, the ubiA homolog of Providencia stuartii, result in high-level aminoglycoside resistance and reduced expression of the chromosomal aminoglycoside 2'-N-acetyltransferase.

The aarE1 allele was identified on the basis of the resulting phenotype of increased aminoglycoside resistance. The aarE1 mutation also resulted in a small-colony phenotype and decreased levels of aac(2')-Ia mRNA. The deduced AarE gene product displayed 61% amino acid identity to the Escherichia coli UbiA protein, an octaprenyltransferase required for the second step of ubiquinone biosynthesis. Complementation experiments in both Providencia stuartii and E. coli demonstrated that aarE and ubiA are functionally equivalent.

An extracellular factor regulating expression of the chromosomal aminoglycoside 2'-N-acetyltransferase of Providencia stuartii.

The chromosomal aac(2')-Ia gene in Providencia stuartii encodes a housekeeping 2'-N-acetyltransferase [AAC(2')-Ia] involved in the acetylation of peptidoglycan. In addition, the AAC(2')-Ia enzyme also acetylates and confers resistance to the clinically important aminoglycoside antibiotics gentamicin, tobramycin, and netilmicin. Expression of the aac(2')-Ia gene was found to be strongly influenced by cell density, with a sharp decrease in aac(2')-Ia mRNA accumulation as cells approached stationary phase. This decrease was mediated by the accumulation of an extracellular factor, designated AR (for acetyltransferase repressing)-factor. AR-factor was produced in both minimal and rich media and acted in a manner that was strongly dose dependent. The activity of AR-factor was also pH dependent, with optimal activity at pH 8.0 and above. Biochemical characterization of conditioned media from P. stuartii has shown that AR-factor is between 500 and 1,000 Da in molecular size and is heat stable. In addition, AR-factor was inactivated by a variety of proteases, suggesting that it may be a small peptide.

aarC, an essential gene involved in density-dependent regulation of the 2'-N-acetyltransferase in Providencia stuartii.

The 2'-N-acetyltransferase [AAC(2')-Ia] in Providencia stuartii has a dual function where it is involved in the acetylation of peptidoglycan and certain aminoglycosides. A search for negative regulators of the aac(2')-Ia gene has resulted in the identification of aarC. A missense allele (aarC1) resulted in an 8.9-fold increase in beta-galactosidase accumulation from an aac(2')-lacZ transcriptional fusion. Northern blot analysis demonstrated an increase in aac(2')-Ia mRNA accumulation that was specific to cells at high density. In addition, the aarC1 allele also resulted in a substantial increase in the expression of aarP, a transcriptional activator of the aac(2')-Ia gene. The wild-type aarC gene was isolated by complementation and encodes a predicted protein of 365 amino acids with a molecular mass of 39,815 Da. The predicted AarC protein exhibited 88% amino acid homology to the previously identified GcpE protein of Escherichia coli and 86% homology to a gene product from Haemophilus influenzae. The E. coli gcpE gene was able to functionally complement the aarC1 allele in P. stuartii. The aarC1 allele was identified as a T to G transversion that resulted in a valine to glycine substitution at position 136 in the AarC protein. The aarC gene appears to be essential for cell viability as construction of a disrupted copy (aarC::lacZ) was possible only in cells that carried an episomal copy of aarC or gcpE.

A prospective study of in-line skating: observational series and survey of active in-line skaters--injuries, protective equipment, and training.

OBJECTIVES: 1) To assess the relationship between types of injuries incurred and training and protective equipment worn by adults injured while in-line skating; 2) to observe the type and amount of protective equipment worn by in-line skaters while skating; and 3) to survey active in-line skaters about formal training, protective equipment, and history of injuries incurred, and the effect of such injuries on the protective equipment subsequently worn. METHODS: A prospective study of consecutive adult patients presenting to the ED for evaluation of in-line skating injuries; a consecutive-series observational study of active in-line skaters to assess protective equipment worn; and a survey of selected active in-line skaters. Eighty-five adult patients were included who presented with a history of injury related to in-line skating to the EDs of an urban academic medical center, a suburban academic-affiliated hospital, and a community hospital. Four hundred eleven active in-line skaters on the Chicago lakefront were observed for protective equipment worn, 91 of whom participated in the survey. RESULTS: Of those presenting to the ED with injuries, only 15% indicated that they had received formal in-line skating instruction. Of the ED patients, 50% wore no protective equipment; overall, 6% wore a helmet; 44%, wrist protection; 23%, knee protection; and 19%, elbow protection. Only 2% wore all of the above equipment. The primary mechanism of injury reported was a loss of balance (58%); others included collision with objects (25%), collision with bicycles (11%), and collision with cars (5%). Fractures or dislocations occurred in 48% of the patients; 6% had head injuries necessitating CT scans. Those who wore no protective gear were more likely to require hospital admission (p < 0.05). Of the 411 in-line skaters observed, 157 (38%) wore no protective equipment. Compared with the injured group presenting to the ED, fewer observed participants were without protection (p < 0.05). Among those surveyed, prior injury was not associated with the subsequent use of protective gear. CONCLUSION: Patients who present to the ED for evaluation of in-line skating injuries have a high incidence of fractures/dislocations. Few injured or surveyed in-line skaters had formal training. Use of protective equipment by injured skaters was associated with a decreased likelihood of hospitalization. Observed in-line skaters more commonly wore protective gear than did those who presented to the ED with injuries.

Measuring substance abuse program treatment orientations: the Drug and Alcohol Program Treatment Inventory.

Assessment of therapeutic orientation is a significant problem in substance abuse program evaluation. This study reports the initial results of a new approach to measuring treatment orientation through a self-report survey that focuses on distinctive features of substance abuse treatment orientations. The Drug and Alcohol Program Treatment Inventory (DAPTI) assesses treatment goals and activities specific to eight orientations: AA/12 Step, Therapeutic Community, Cognitive-Behavioral, Insight/Psychodynamic, Rehabilitation, Dual Diagnosis, Medical and Marital/Family Systems. We present findings from a nationwide assessment of 327 Veterans Administration (VA) Substance Abuse treatment programs that demonstrate promising subscale internal consistency, discriminant validity, and concurrent validity. In addition, the DAPTI distinguishes between programs with independently verified orientations and between inpatient, extended care, outpatient, and methadone maintenance programs. The DAPTI may be helpful in systematically assessing differences in treatment orientations between different types of programs, such as inpatient, community residential, and outpatient care.

Inpatient treatment for substance abuse patients with psychiatric disorders: a national study of determinants of readmission.

This study examined the patient case mix and program determinants of 6-month readmission rates and early treatment dropout for 7,711 VA inpatients with both substance abuse and major psychiatric disorders treated in one of 104 substance abuse programs. Patients were treated in one of three types of inpatient programs: explicitly designed dual diagnosis specialty programs, substance abuse programs with a dual diagnosis psychotherapy group or standard substance abuse programs. Dual diagnosis specialty programs differed from regular substance abuse programs in that they had a more severe case mix, a higher 180-day readmission rate, greater dual diagnosis treatment orientation, used more psychotropic medication, had longer lengths of stay, had greater tolerance of relapse and medication noncompliance, and a higher rate of psychiatric aftercare in the 30 days after discharged. Programs with less severe case mix, longer intended and actual length of stay, lower 7-day dropout rates, greater tolerance of problem behavior, 12-step groups, and higher immediate postdischarge utilization of outpatient mental health treatment lower 180-day readmission rates. Programs with less severe patient case mix, more use of psychotropic medications but less of methadone and antabuse, less varied and diverse treatment activities, and low use of patient-led groups had lower dropout rates.

A randomized, double-blind, phase I/II trial of tumor necrosis factor and interferon-gamma for treatment of AIDS-related complex (Protocol 025 from the AIDS Clinical Trials Group).

To determine safety and efficacy of tumor necrosis factor (TNF) and interferon-gamma (IFN gamma) in the treatment of patients with acquired immunodeficiency syndrome (AIDS)-related complex, a randomized, double-blind study was conducted. Twenty-five patients with AIDS-related complex and CD4 lymphocytes less than or equal to 500 x 10(6)/L attended an AIDS Clinical Trials Unit of a tertiary referral center. Patients were administered tumor necrosis factor (TNF) (10 micrograms/m2) or IFN gamma (10 micrograms/m2), or both intramuscularly three times weekly for 16 weeks. Side effects from all three preparations included fever, constitutional symptoms, and local reactions. No significant hematologic, hepatic, renal, or coagulation abnormalities were observed. CD4 lymphocyte counts, beta 2-microglobulin, p24 antigen levels, and anti-p24 antibody did not change significantly during therapy. Similarly, no significant change was noted in rates of HIV isolation from peripheral blood mononuclear cells or plasma. TNF and IFN gamma were tolerable after premedication with acetaminophen; however, no significant change in markers of human immunodeficiency virus infection was demonstrated. These cytokines alone do not appear to be of benefit, nor do they appear to hasten the progression of HIV infection.