Prevalence and correlates of "popper" (amyl nitrite inhalant) use among HIV-positive Latinos living in the U.S.-Mexico border region.

Poppers (nitrite inhalants) are legal, commonly used by men who have sex with men, and associated with HIV acquisition, yet research is lacking on popper use and associated adverse outcomes. People living with HIV (PLWH) in the U.S.-Mexico border region lead binational lives, including accessing care and having sex and drug use partners on both sides of the border, with broad personal and public health implications. Understanding popper use provides crucial information to guide policy and develop targeted interventions for binational PLWH. We examine prevalence and correlates of popper use among HIV-positive Latinos in the border region, an underserved population at risk for poor health outcomes. This cross-sectional study recruited a convenience sample from agencies in San Diego and Tijuana to complete quantitative surveys. Participants (N = 121) were primarily male (82.6%) and gay/bisexual (62%). Lifetime substance use (excluding cannabis) was reported by 72% of participants, and 25.6% reported lifetime popper use. Individuals recruited in the U.S. were significantly more likely to report use of poppers than were participants recruited in Mexico. Our regression model found that identifying as gay/bisexual and having bought, sold, or traded sex for money, drugs, or other goods were independently associated with popper use. Findings shed light on the profile of individuals who use poppers and lay the foundation for further research to understand the context of popper use as it relates to high-risk behavior among PLWH in this region of high transborder mobility. Binational collaborative approaches are needed to improve regional HIV care outcomes and reduce transmission risk.

A Study of the Longitudinal Patterns of Stimulant and Amyl Nitrite Use and Sexual Behavior Pre- and Post-HIV Seroconversion Among MSM.

The use of stimulant drugs alone or in combination with amyl nitrites (stimulant/nitrites) has been associated with higher rates of risky sexual behavior and predictive of HIV infection among men who have sex with men. However, the temporal pattern of stimulant/nitrite use pre- and post-seroconversion has not been well established. This study assessed changes in stimulant/nitrite use and risky sexual behavior among seroconverting MSM over time. Data were collected in the Baltimore-Washington, DC; Pittsburgh; Chicago; and Los Angeles sites of the Multicenter AIDS Cohort Study (MACS), a longitudinal study of the natural history of HIV infection among MSM. We used propensity scores to select 1044 MSM from 7087 MACS participants composed of 348 seroconverting, 348 seronegative, and 348 seroprevalent participants matched on demographics, recruitment cohort, and study visits. We centered up to four-years of semi-annual data around the seroconversion visit of the seroconverting case within each matched group of participants. Mixed effects regressions estimated the effects of serostatus, recruitment cohort, and time on self-reported stimulant/nitrite use, numbers of male intercourse partners, and numbers of unprotected receptive anal intercourse (URAI) partners. Covariates included demographics, binge drinking, and marijuana use. Seroconverters had the highest odds of stimulant/inhaled nitrite use (AOR 10.3, CI 4.8-22.0), incident rates of intercourse (IRR 1.6, CI 1.3-2.1), and URAI partners (IRR 5.1, CI 3.5-7.3). All participants decreased drug use and sexual risk behavior over time. However, the decreases were largest for seroconverters who nevertheless maintained the highest rates of stimulant/nitrite use and sexual risk. Cohort-related effects were associated with sharp reductions in stimulant/nitrite use and URAI in the early 1990s that rebounded considerably within the first decade of the 2000s. Although all participants decreased risky sexual behavior and stimulant and/or nitrite use over time, seroconverters had the largest decreases. There was no evidence for abrupt or substantial increases in drug use or risky sex post-seroconversion. However, there was substantial variation at the individual level, with the factors underlying this variation not well understood and worth further study. Moreover, stimulant/nitrite use and risky sexual behavior appear to have been strongly influenced by contextual historical and socio-cultural effects. The manner in which contextual factors influence individual behavior is also not well understood and also warrants further study.

The Amyl Nitrite Expectancy Questionnaire for Men who have Sex with Men (AEQ-MSM): a measure of substance-related beliefs.

A measure of perceived reinforcement associated with amyl nitrite was developed and evaluated among gay and bisexual men. This is the first known expectancy measure to date for this drug class. The Amyl Nitrite Expectancy Questionnaire for Men who have Sex with Men (AEQ-MSM) was completed online by 102 gay and bisexual men, between 2006 and 2008 in Queensland, Australia. The AEQ-MSM demonstrated good psychometric properties and was associated with consumption patterns. Factor analysis revealed three distinct reinforcement domains: "Enhanced sexual desire and pleasure," "Disorientation," and "Sexual negotiation." Limitations include sampling via self-selection, recruitment through health centers and self-report data. Implications for sexual activity and risk-taking, including reducing associated harm (e.g., HIV transmission), and future directions are discussed.

Pharmacologic interrogation of patients with esophagogastric junction outflow obstruction using amyl nitrite.

BACKGROUND: The Chicago Classification of esophageal motility includes a group of patients who show evidence of esophagogastric junction outflow obstruction (EGJOO) as demonstrated by elevated integrated relaxation pressure (IRP) and preserved peristalsis. Our aim is to classify EGJOO patients based on response to amyl nitrite (AN) during high-resolution manometry. METHODS: Patients were considered to have true EGJOO if elevated IRP during supine swallow persisted in the upright position and was associated with high intrabolus pressure. The EGJ response to AN was compared between patients with achalasia type 2 (A2) and normal esophageal motility. Based on the relaxation gain (deglutitive IRP-AN IRP) value that best discriminated these two groups (10 mm Hg), patients with true EGJOO were categorized as being in either the AN-responsive (AN-R) or AN-unresponsive (AN-U) subgroups. KEY RESULTS: In the group of 49 patients with true EGJOO, the AN response classified 27 patients (IRP = 25 ± 10 mm Hg) with AN-R and 22 patients (IRP = 20 ± 5 mm Hg) with AN-U (P = 0.2). In AN-R, AN produced a relaxation gain and rebound after-contraction response at the EGJ comparable to A2 patients. AN-U patients had an elevated IRP after AN and a relaxation gain similar to normal esophageal motility patients. AN-U patients were obese and had higher prevalence of sleep apnea (P < 0.05). CONCLUSIONS: Among patients with true EGJOO, only half have pharmacologic evidence of impaired LES relaxation. Pharmacologic interrogation of the EGJ is thus necessary to identify the subgroup of EGJOO patients who could be expected to benefit from LES ablative therapies.

Following Lives Undergoing Change (Flux) study: Implementation and baseline prevalence of drug use in an online cohort study of gay and bisexual men in Australia.

BACKGROUND: Drug use among gay and bisexual men (GBM) is higher than most populations. The use of crystal methamphetamine, erectile dysfunction medication (EDM), and amyl nitrite have been associated with sexual risk behaviour and HIV infection among gay and bisexual men (GBM). OBJECTIVE: This paper describes an online prospective observational study of licit and illicit drug use among GBM and explores baseline prevalence of drug use in this sample. Capturing these data poses challenges as participants are required to disclose potentially illegal behaviours in a geographically dispersed country. To address this issue, an entirely online and study specific methodology was chosen. METHODS: Men living in Australia, aged 16.5 years of age or older, who identified as homosexual or bisexual or had sex with at least one man in the preceding 12 months were eligible to enrol. RESULTS: Between September 2014 and July 2015, a total of 2250 participants completed the baseline questionnaire, of whom, 1710 (76.0%) consented to six-monthly follow-up. The majority (65.7%) were recruited through Facebook targeted advertising. At baseline, over half (50.5%) the men reported the use of any illicit drug in the previous six months, and 28.0% had used party drugs. In the six months prior to enrolment, 12.0% had used crystal methamphetamine, 21.8% had used EDM, and 32.1% had used amyl nitrite. Among the 1710 men enrolled into the cohort, 790 men had used none of these drugs. CONCLUSION: Ease of entry and minimal research burden on participants helped ensure successful recruitment into this online cohort study. Study outcomes will include the initiation and cessation of drug use, associated risk behaviours, and health consequences, over time. Results will provide insights into the role gay community plays in patterns of drug use among GBM.

Provocation of latent left ventricular outflow tract gradients with amyl nitrite and exercise in hypertrophic cardiomyopathy.

Amyl nitrite may be used to provoke latent gradients in patients with hypertrophic cardiomyopathy (HC) without significant resting outflow tract gradients, but afterload reduction may not be comparable to a more physiologic stressor such as symptom-limited exercise testing. This study compared the ability of amyl nitrite and exercise testing to provoke outflow tract gradients in 57 patients (40 men and 17 women, mean age +/- SD 49 +/- 16 years) with HC (septal thickness 19 +/- 5 mm, average resting gradient 13 +/- 10 mm Hg) who underwent echocardiography at rest, after amyl nitrite inhalation, and after maximal exercise. No significant gradient (< 50 mm Hg) was induced after either provocation in 26 patients (46%); in 15 patients (26%), inducibility was achieved after both stressors, in 6 (11%) after exercise only, and in 10 (18%) after amyl only. Patients with amyl-induced gradients differed from those in whom gradients were noninducible on the basis of smaller outflow tract dimensions (p < 0.001), larger resting gradients (p < 0.001), and a greater prevalence of "septal bulge" morphology (p = 0.02). Those with exercise-induced gradients were able to attain a greater workload (p = 0.07), have larger resting gradients (p = 0.02), and also tended to have a septal bulge morphology (p < or = 0.01). Although outflow tract obstruction increased to similar levels after amyl nitrite (49 +/- 39 mm Hg) and symptom-limited exercise (47 +/- 39 mm Hg), gradients induced by exercise and amyl correlated poorly (r = 0.54).(ABSTRACT TRUNCATED AT 250 WORDS)

Amyl nitrite induced acute haemolytic anaemia in HIV-antibody positive man.

Volatile nitrites (amyl and butyl) are popular recreational drugs, especially in the homosexual population. Haemolytic anaemia is a rare complication of nitrite inhalation and occurs when the reducing capacity of the red cell enzymes is overcome by the oxidizing effect of the nitrite. We describe here a patient with HIV infection who developed a profound haemolytic anaemia after repeated inhalation of large quantities of amyl nitrite.

Baroreflex function in uremic and hypertensive man.

Human hypertension has been related to abnormalities of autonomic blood pressure regulation. In order to characterize a possible defect, we have studied several aspects of reflex autonomic circulatory control in normal subjects, patients with primary hypertension, and two types of subjects with uremia and elevated blood pressure. Phenylephrine infusion (a measurement of baroreceptor response to high pressure stimulus) resulted in similar hemodynamic changes in all types of subjects. However, all groups of patients exhibited significantly different hemodynamic responses to amyl nitrite inhalation (an index of baroreceptor response to low pressure stimulus). These results suggest that patients with uremia and those with primary hypertension differ from each other and normal subjects regarding baroreceptor reflex function. Furthermore, one type of uremic patient may have a neurogenic component to their hypertension similar to experimental animals following surgical section of afferent baroreceptor nerves.

Effects of acute inhalation exposure to isoamyl nitrite on the hypothalamo-pituitary-adrenal axis in male Sprague-Dawley rats.

Isoamyl nitrite (IAN) is a member of the family of volatile organic nitrites that exert vasodilatory effects and have recently exhibited a considerable potential for inhalation abuse. In an effort to provide mechanistic insight into the neurotoxic effects and abuse potential of these agents, the present study was designed to evaluate the acute effects of IAN on the hypothalamo-pituitary-adrenal (HPA) axis. Attempts were also made to correlate the neuroendocrine effects of IAN with its pharmacokinetic profile. Male Sprague-Dawley rats were exposed to 600 or 1200 ppm IAN by inhalation for 10 or 30 min. Following exposure, adrenocorticotropic hormone (ACTH) and corticosterone in plasma and corticotropin-releasing factor (CRF) in three brain regions (hypothalamus, hippocampus, and frontal cortex) were determined by radioimmunoassay. Levels of IAN in the three brain regions as well as in blood were measured by gas chromatography to determine the target tissue concentrations responsible for neuroendocrine changes. Uptake of IAN into blood and all brain regions was very rapid, as stable concentrations were achieved within 10 min of exposure and maintained for 30 min of continuous inhalation. Plasma corticosterone decreased significantly after 10 min inhalation of both IAN doses, and returned to control levels after 30 min. Moreover, plasma ACTH was significantly increased by 10 and 30 min of exposure to 600 and 1200 ppm IAN, while hypothalamic CRF increased significantly after 30 min of exposure to the 600 ppm dose. These latter findings suggest activation of the hypothalamus and pituitary due to a reduction in negative feedback resulting from the initial decrease in corticosterone. Although plasma ACTH was greatly increased after 30 min, plasma corticosterone levels were unchanged, indicating that IAN primarily acts to inhibit the synthesis or secretion of adrenal steroids and that activation of the HPA axis is not involved in the behavioral manifestations of IAN inhalation. These compensatory effects of HPA axis regulation, and possibly the vasodilatory properties of IAN, also likely precluded the establishment of definitive relationships between observed changes in hormone levels and blood or regional brain concentrations of the inhalant.

Detection of coronary artery disease by vasodilator thallium imaging of the heart with amyl nitrite inhalation: a pilot study.

Thallium imaging of the heart using dipyridamole-induced coronary arteriolar vasodilation has proven to be an effective means of detecting significant coronary stenosis. However, intravenous dipyridamole has not yet been made available for general use. We therefore examined the feasibility of substituting amyl nitrite inhalation as an arteriolar vasodilator prior to thallium imaging. Seventeen patients, all of whom had catheterization-proven coronary stenosis, inhaled amyl nitrite for 2-5 min. Thallium was injected after 45-60 s of inhalation. Completion of inhalation was followed immediately by planar imaging. Of 6 patients who inhaled amyl nitrite for at least 4 min, 5 had moderate or severe image defects on immediate scans which completely resolved on delayed scans. Only 3 of 11 who inhaled amyl nitrite for 2 min or less prior to scanning had similarly positive tests. Overall sensitivity for significant stenosis was 8 of 17 (47%). Inhalation was well tolerated with only one episode of angina and hypotension. We conclude that amyl nitrite inhalation for at least 4 min may offer an effective and readily available alternative to intravenous dipyridamole for vasodilator imaging of the heart.

Subtle features of the hemodynamic response to amyl nitrite inhalation: new aspects of an old tool.

Although amyl nitrite inhalation (ANI) antedates all current short acting vasodilators as a clinically useful pharmacologic stressor, few clinicians are aware of the subtle hemodynamic actions of this agent. This study examined transients in left and right heart hemodynamics after ANI in seven men (ages 44 +/- 7 years) undergoing elective cardiac catheterization. High-fidelity central aortic (AoP), left ventricular (LVP), pulmonary artery (PAP), right ventricular (RVP), and right atrial (RAP) pressures were simultaneously recorded from left and right heart multisensor catheters. As expected, ANI caused an acute fall in Ao pressure (27%; p < 0.01) and reflex tachycardia (p < 0.001). Little change was noted in PAP, RVP, RAP, or LV end-diastolic pressures or the time constant of LV isovolumetric relaxation (tau). LV ejection time decreased 23 +/- 10 ms (p < 0.05) and RV ejection time did not change. Baroreflex sensitivity was similar during pressure fall and recovery (6.4 +/- 4.5 vs. 6.1 +/- 3.6 ms/mmHg), however hysteresis (p < 0.05) was noted. Aortic pressure waveforms also changed following ANI. Changes were determined to be in part a consequence of the attenuation and delay in arterial wave reflections. This study extends the understanding of the complex nature of the hemodynamic response associated with ANI.

Pulsus alternans. Its response to amyl nitrite inhalation.

Marked pulsus alternans was observed in a patient with primary congestive cardiomyopathy. Afterload reduction with amyl nitrite caused the disappearance of the pulsus alternans. Investigation by phonocardiography, echocardiography, systolic time interval measurement and cardiac catheterization disclosed that during pulsus alternans the weak beat originated following a short diastolic filling period and generated much lower contractile force. This report may be relevant to the currently accepted concepts of afterload reduction in the treatment of chronic congestive heart failure.

Expanding the indications for septal myectomy in patients with hypertrophic cardiomyopathy: results of operation in patients with latent obstruction.

OBJECTIVE: Many patients with symptomatic hypertrophic cardiomyopathy have minimal left ventricular outflow tract gradients, and there is uncertainty whether their limitation is due to diastolic dysfunction or labile outflow tract obstruction. The purpose of this study was to characterize the clinical presentation and outcome of septal myectomy in patients with hypertrophic cardiomyopathy and latent obstruction. METHODS: Among 749 patients who underwent septal myectomy, 249 had latent obstruction with minimal (0-30 mm Hg) resting gradients preoperatively. All were symptomatic and had more severe left ventricular outflow tract obstruction provoked by Valsalva maneuver or amyl nitrite inhalation during Doppler echocardiography or by stimulation with isoproterenol during catheterization. Clinical characteristics, survival, and functional outcome of these patients were compared with those of 500 patients with more severe resting left ventricular outflow tract obstruction who underwent myectomy during the same period. RESULTS: Compared with those with severe obstruction, more patients with latent obstruction were male (63% vs 52%, P < .003), but ages were similar (53 ± 14 years vs 52 ± 15 years). Preoperative symptoms and functional limitation were similar in the 2 groups with 86% and 85%, respectively, having New York Heart Association class III or IV disability. Among patients with latent obstruction, mixed venous oxygen saturation was 61.6% ± 19.0% of predicted compared with 56.8% ± 17.3% for those with severe resting obstruction (P < .008). Septal thickness was less in patients with latent obstruction (20 ± 9 mm vs 22 ± 15 mm, P < .001). Early mortality was 1% in each group, and survival at 5 and 10 years was 93% and 87%, respectively, for patients with latent obstruction compared with 93% and 74%, respectively, for patients with severe resting obstruction preoperatively (P = .34). Self-reported late functional status was similar; 3 to 5 years postoperatively, 81% of patients with latent obstruction preoperatively were in New York Heart Association class I or II compared with 77% of patients with severe resting obstruction. CONCLUSIONS: Patients with obstructive hypertrophic cardiomyopathy who have low resting gradients and latent obstruction may have limiting symptoms comparable to those of patients with more severe resting gradients. Septal myectomy should be offered to these patients because survival and symptom relief are excellent, suggesting that dynamic obstruction is the major hemodynamic problem rather than diastolic dysfunction.

Does amyl nitrite have a role in the management of pre-hospital mass casualty cyanide poisoning?

CONTEXT: Amyl nitrite has been recommended as a cyanide antidote for several decades. Its antidotal properties were initially attributed to induction of methemoglobin and later to a nitric oxide mediated hemodynamic effect. The ease of administration and alleged rapid clinical effect would recommend its wide use in the pre-hospital management of mass casualty cyanide poisoning; yet there are concerns regarding the use of amyl nitrite for this indication. OBJECTIVE: Review the data on amyl nitrite in cyanide poisoning and evaluate its efficacy and safety in mass casualty cyanide poisoning. METHODS: A literature search utilizing PubMed, Toxnet, textbooks in toxicology and pharmacology, and the bibliographies of the articles retrieved identified 17 experimental studies and human reports on the use of amyl nitrite in cyanide poisoning, and 40 additional articles on amyl nitrite's properties and adverse effects. One paper was excluded as it was a conference abstract with limited data. MECHANISMS OF ACTION: The antidotal properties of amyl nitrite were attributed initially to induction of methemoglobinemia and later to nitric oxide mediated vasodilation. EXPERIMENTAL STUDIES: Animal studies on the use of amyl nitrite in cyanide poisoning are limited, and their results are inconsistent, which makes their extrapolation to humans questionable. HUMAN STUDIES: Clinical reports are limited in number and the part played by amyl nitrite relative to the other treatments administered (e.g. life support, sodium nitrite, and sodium thiosulfate) is unclear. ADVERSE EFFECTS: Amyl nitrite can be associated with potentially serious adverse reactions such as hypotension, syncope, excessive methemoglobinemia, and hemolysis in G6PD deficient patients. These effects are more pronounced in young children, in the elderly, and in patients with cardiac and pulmonary disorders. Dose regimen. The method of administration of amyl nitrite (breaking pearls into gauze or a handkerchief and applying it intermittently to the victim's nose and mouth for a few minutes) is not easily controlled, might result in under- or over-dosing, can prevent the caregiver from administering life support, and possibly expose him/her to amyl nitrite's adverse effects. CONCLUSIONS: Administration of amyl nitrite in mass casualty cyanide poisoning can result in unnecessary morbidity and may interfere with the proper management of the incident and the required supportive treatment and rapid evacuation. In the authors' opinion these drawbacks make the use of amyl nitrite in pre-hospital mass casualty cyanide poisoning unwarranted.