Using social indicators to predict addiction.

Because of cost and other constraints, states often find it difficult to estimate need for treatment of alcohol-related problems from routine surveys. The social undesirability of illegal drug use makes the assessment of need for treatment of their use even more difficult. This paper uses independently obtained treatment need estimates to provide parameters for short-term prediction. We obtained the parameters by regressing the proportions of people addicted to alcohol (or drugs) in counties on social-indicator-based relative treatment need estimates for alcohol (or drugs). In addition to integrating estimates coming from independent sources, our approach presents an important tool for planning and resource allocation.

Changes in HIV risk behavior among injecting drug users: the impact of 21 versus 90 days of methadone detoxification.

OBJECTIVE: To evaluate the hypothesis that long-term methadone detoxification would produce greater HIV risk reduction among injecting drug users (IDU) than short-term detoxification. DESIGN: Random assignment to 21 or 90 days of free detoxification. SETTING: Storefront offices in two cities, with referrals to outpatient methadone detoxification. PARTICIPANTS: Out-of-treatment IDU (n = 1803), recruited through street outreach and word of mouth, between April 1990 and March 1991. Of these, 62.6% were successfully located for 6-month follow-up. MAIN OUTCOME MEASURES: Self-reported drug injection and sexual practices at baseline and follow-up. RESULTS: Substantial reductions in risk behavior were observed at follow-up. Substantial percentages of subjects reported less frequent drug injection (54%), use of shooting galleries (85%), needle-sharing (67%), and number of sex partners (73%), and more frequent use of bleach to disinfect needles (67%) and condom use (31%). There were no significant differences in behavioral change between 21 and 90-day treatment, and subjects who entered treatment did not report significantly greater risk reduction than untreated subjects. Discriminant analyses showed a marginal effect for duration of treatment on risk reduction, although results were inconsistent. CONCLUSIONS: Large scale behavioral risk reduction appears to be occurring in this population regardless of treatment condition. In minimal service methadone detoxification, subjects treated under a longer-term detoxification protocol demonstrated no greater risk reduction than those receiving short-term detoxification.

On the construction of a relative needs assessment scale.

The Social Dysfunction Scale, originally framed by Simeone et al., is a major first step in the introduction of objectivity to a complex subject often guided by political concerns rather than empirical findings. However, it is too heavily influenced by population sizes of the geographic units. The Relative Needs Assessment Scale proposed here is more flexible and corrects that problem by using weights that set a balance between the burden of the substance use(r) problem and the size of the "population at risk" in the geographic unit. Assuming that a fairly good mix of indicators is identified for substance use(r) problems, the alternative scale provides a better estimate of relative needs for resources.

Compliance with AZT treatment regimen of HIV-seropositive injection drug users: a neglected issue.

Although treatment with zidovudine (AZT) is now recommended for asymptomatic and symptomatic HIV-infected persons with CD4+ cell counts of 0.20 to 0.50 x 10(9)/L and under, data gathered from a small convenience sample of current and former injection drug users with AIDS in the New York City metropolitan region suggest that noncompliance with HIV/AIDS-related therapeutic regimen may be common in this population. This paper enumerates the reasons for noncompliance offered by these informants, reviews the general literature on treatment compliance to identify additional potential reasons for non-adherence to AZT treatment regimen, and outlines some suggestions for future research into this important issue that may prompt changes in the antiviral delivery system.

Prospective evaluation of a model of risk for HIV infection among injecting drug users.

Data on 3016 out-of-treatment injecting drug users (IDUs) were analyzed in order to replicate findings from an earlier study on risk factors for HIV infection (Iguchi et al., 1992) and evaluate a model for estimating probability of infection. Logistic regression analyses yielded a set of risk factors highly consistent with previous findings. A logistic function was used to estimate subjects' probabilities of infection, and these estimates were strongly correlated with actual HIV prevalence in both the original and current samples. The current study represents a successful replication of earlier findings and supports the validity of the risk model.

What is the addicts' grapevine when there's 'bad dope'? An investigation in New Jersey.

After a rash of fatal overdoses among drug users that was attributed to the synthetic narcotic analgesic fentanyl, the New Jersey Department of Health conducted street interviews with 160 injection drug users in an attempt to identify the channels through which this population had heard about the outbreak and to gauge drug addicts' responses to the incident. The results of the investigation suggest that the drug users learn about such severe threats to health from a variety of sources. The frequency with which some of these sources are reported differs significantly according to the sex of the drug user and, even when sex is controlled, the frequency may vary substantially from city to city in a relatively limited geographic area. Although television was, for this population, a more important source of information about the outbreak than was any other formal means of communication, drug users did not regard TV as a reliable source of good information about "bad dope." Moreover, it does not appear that broadcasts of public warning messages about such substances are a guarantee that addicts will not search for the drug. The data reported in this study point up a need for health officials' greater understanding of the channels through which drug users receive information on threats to their health. The study also provides an understanding of how public health messages are perceived and processed by needle users. The final lesson is the need for close collaboration among drug enforcement personnel, testing laboratories, and health officials in the various affected locales to clarify the public health message.

Dual inhibition of angiotensin-converting enzyme and neutral endopeptidase in rats with hypertension.

Angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP), are two mechanistically similar enzymes involved in the metabolism of several vasoactive peptides. Selective inhibitors of ACE are effective antihypertensive agents in high-renin, renovascular rats and normal-renin, spontaneously hypertensive rats (SHR), but are not effective in the low-renin, deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In contrast, NEP inhibitors are only effective in the low-renin model of hypertension. Treatment with a combination of selective inhibitors or with a dual inhibitor of both enzymes produces an antihypertensive response regardless of basal plasma renin activity. In this study, we compared the activities of MDL 100,173, a novel subnanomolar inhibitor of both ACE and NEP, with those of equimolar doses of captopril, a selective ACE inhibitor, following intravenous administration in these three rat models of hypertension. Treatment with MDL 100,173 significantly lowered blood pressure compared to vehicle treatment in all three models, whereas captopril treatment lowered blood pressure in the renovascular and SHR models only. Administration of MDL 100,173 also significantly elevated diuresis and natriuresis compared to either vehicle or captopril treatment in the SHR and DOCA-salt rats. Urinary excretion of atrial natriuretic peptide (ANP) was increased by MDL 100,173 treatment in all three models of hypertension. Treatment with captopril did not alter urine, sodium, or ANP excretion in any of the models. However, plasma-renin activity was elevated by both MDL 100,173 and captopril '''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''' ''''''''

Reduction in endotoxin-induced organ dysfunction and cytokine secretion by a cyclic nitrone antioxidant.

Multiple organ dysfunction (MOD) is the leading cause of mortality in septic patients with circulatory shock. Recent evidence suggests that the overproduction of the cytokine, tumor necrosis factor-alpha(TNF), and oxygen free radical molecules may mediate the progression of sepsis to MOD and death. In this study, we have examined the ability of MDL 101,002, a free radical scavenger, to reduce organ dysfunction and cytokine secretion induced by lipopolysaccharide (LPS) administration in rats. Treatment with MDL 101,002(10-60 ng/kg, i.p.) 30 min prior to an LPS challenge resulted in a dose-dependent reduction in several markers indicative of organ dysfunction and mortality. MDL 101,002 markedly decreased LPS-induced liver and kidney damage as indicated by serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) or urea and creatinine, respectively. MDL 101,002 also prevented LPS-induced pulmonary edema, but did not prevent leukopenia and only partially reduced thrombocytopenia. Associated with these improvements in organ dysfunction and survival was a modest decrease in LPS-stimulated interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) secretion and a marked ( > 90%) inhibition of TNF secretion by MDL 101,002. The data are consistent with a role for oxygen free radicals in the development of endotoxin-induced organ dysfunction and shock and suggest that free radical scavengers could reduce the mortality consequent to sepsis by decreasing organ dysfunction, at least in part, through a reduction in free radical stimulated cytokine secretion.

Seroprevalence and risk factors associated with HTLV-I/II infection in injection drug users in northern New Jersey.

Data from an AIDS Demonstration Research project in Paterson, NJ, that enrolled out-of-treatment injection drug users (IDUs) were analyzed to detect demographic patterns and risk factors associated with infection with human immunodeficiency virus (HIV) and human T-lymphotropic virus types I or II (HTLV-I/II). Of 410 IDUs screened, 44.2% were HIV-positive and 19.3% were HTLV-I/II-positive. African-Americans were significantly more likely than other racial groups to be HTLV-I/II-seropositive and to be HIV-seropositive. Over one-fifth of African-Americans--but no Latinos or whites--were doubly infected with HIV and HTLV-I/II. In logistic regression analysis, African-American race, long-term injection drug use, and age were significant predictors of HTLV-I/II-seropositivity. While the associations between recent needle practices and HTLV-I/II-seropositivity fell short of significance, the trends in the data were consistent with a hypothesis that HTLV-I/II is transmitted through the sharing of injection equipment. Public health implications of the data are discussed.

Protective effects of a cyclic nitrone antioxidant in animal models of endotoxic shock and chronic bacteremia.

Evidence of a role for oxygen-derived free radicals in the pathophysiology of endotoxic shock has been found in animal models. However, the importance of free radicals in chronic models of bacterial infection has not been examined. In this study a novel nitrone radical spin trap is described and its activity in animal models of endotoxic shock and chronic bacteremia were explored. MDL 101,002 is a cyclized variant of alpha-phenyl N-tert-butyl nitrone (PBN), an established spin trap. MDL 101,002 can react with free radicals to form persistent adducts as demonstrated by electron paramagnetic resonance (EPR) spectroscopy. This agent is about 10 times more potent than PBN as an in vitro antioxidant and scavenger of hydroxyl radicals. In a rat endotoxic shock model MDL 101,002 (3-30 mg/kg, i.p.) administered 30 min prior to endotoxin (30 mg/kg, i.p.) treatment reduced mortality in a dose-dependent manner. Peroxide-enhanced chemiluminescence in hepatic homogenates from endotoxin treated rats was elevated indicating that oxidative stress and antioxidant depletion was increased. Importantly, treatment with MDL 101,002 (30 mg/kg, i.p.) 30 min prior to, and 120 min following endotoxin, minimized the increase in chemiluminescence. MDL 101,002 also reduced mortality in a model of chronic bacteremia employing implantation of infected fibrin clots into the peritoneal cavity of gentamicin-treated leukopenic rats. MDL 101,002 (2.5 mg/kg/hr) increased survival from 24% to 52% in these rats. These data are consistent with a role for free radicals in the pathophysiology of endotoxic shock and suggest free radicals are also important mediators in chronic models of sepsis.

Dihydropyridine Ca2+ channel agonists and antagonists potentiate ultraviolet light-induced relaxation through cyclic GMP formation in porcine coronary artery.

We investigated the mechanisms of dihydropyridine Ca2+ channel agonist potentiation of ultraviolet (UV) light-induced smooth muscle relaxation in porcine coronary artery rings. Rings contracted with the dihydropyridine Ca2+ channel agonist, (+)-S-202-791, were more sensitive to relaxation in response to UV light than were rings contracted with KCl or histamine. Relaxation of (+)-S-202-791-contracted rings was independent of the presence of endothelium and was associated with cyclic GMP formation. Methylene blue (MB) prevented UV light-induced relaxation and cyclic GMP formation. UV light-induced relaxation of histamine and KCl contracted rings and cyclic GMP formation were potentiated by (+)-S-202-791 or the Ca2+ channel antagonist, (-)-R-202-791. Exposure of (+)-S-202-791 to UV light decreased its contractile potency. The data suggest that UV light-induced relaxation of vascular smooth muscle (VSM) is mediated through cyclic GMP formation and that potentiation of UV light-induced relaxation by dihydropyridine Ca2+ channel agonists results from their breakdown to a compound(s) that activates guanylate cyclase.

Interpreting HIV seroprevalence data from a street-based outreach program.

A total of 4,375 subjects were recruited through continuous street outreach over 31 months for interviews on HIV-related risk behavior and HIV-antibody testing. Changes over time among sampled subjects with respect to HIV infection and HIV-risk behavior have been examined retrospectively, and significant and consistent trends noted across successive cohorts. Although overall 42% of the sample tested HIV antibody-positive, HIV infection exhibited a consistent downward trend from 60% in the first quarter year of interviewing to 22% in the final quarter year. Scores on a multivariate index of HIV risk also declined significantly. Mean age, proportion of Black subjects, mean length of drug injection career, frequency of drug injection, and the use of shooting galleries all declined significantly across quarters as well. We argue that these observed differences result from a systematic sampling bias inherent in our outreach-driven sampling procedures, which initially favored recruitment of IDUs with greater behavioral and demographic risk for HIV.

A comparison of male and female intravenous drug users' risk behaviors for HIV infection.

Despite the central role played by female intravenous drug users (IVDUs) in the worsening AIDS statistics of states in the northeastern United States, the relative paucity of research into the HIV risk behaviors--particularly risky needle practices--of female drug injections has left significant gaps in researchers' understanding of how and to what extent such women may differ in their risks from their better-studied male counterparts. This study, derived from a sample of 769 out-of-treatment IVDUs residing in an area (Paterson, New Jersey) characterized by high levels of AIDS and HIV infection among drug users, attempts to address this lacuna in the research literature by comparing the drug usage, AIDS knowledge, and needle and sexual behaviors of male and female IVDUs that place them at risk for HIV infection. In this sample, gender was found to be unrelated to HIV serostatus, injection frequency and injected drug of choice, and to most dimensions of knowledge about AIDS and the means of HIV transmission. Overall, it appears that the average Paterson female IVDU may be at greater risk for HIV infection as a result of involvement with a drug-using sex partner than because of especially risky needle practices, for females in this sample were significantly more likely than males to report injecting with a sex partner in the previous 6 months, and female IVDUs with one sex partner were more than twice as likely as males with one partner to report that this individual was an IVDU. Condom use was relatively rare, particularly among those with one partner. Moreover, female IVDUs were significantly more likely than males to be daily users of crack cocaine, and significantly more likely to report poorer health. However, current needle and sexual practices were found to be unrelated to HIV seropositivity among both males and females. In logistic regression analysis, only length of IV drug involvement was found to be independently associated with HIV seropositivity for both sexes. Implications of the data for future prevention efforts aimed at female IVDUs are discussed.

Characterization of a dual inhibitor of angiotensin I-converting enzyme and neutral endopeptidase.

In the present study we characterize key activities of an agent designed to simultaneously inhibit angiotensin I-converting enzyme (ACE) and neutral endopeptidase (NEP). MDL 100,240 is a thioester prodrug of MDL 100,173, which is a potent competitive inhibitor of both ACE and NEP in vitro. MDL 100,240 was shown in an ex vivo study to inhibit both of these enzymes in rat kidney. When administered to anesthetized rats, MDL 100,240 enhanced the effect of infused ANP on blood pressure, diuresis and natriuresis and of infused bradykinin on blood pressure. Moreover, MDL 100,173 and MDL 100,240 inhibited the pressor response to angiotensin I. These results indicate that MDL 100,173 and its prodrug, MDL 100,240, produced effects, in vivo, consistent with inhibition of both ACE and NEP.

Identification of a specific receptor for interleukin-1 in vascular smooth muscle cells: regulation by interleukin-1 and interleukin-6.

A fluorescently labeled ligand was utilized to establish the existence of an interleukin-1 (IL-1) receptor in vascular smooth muscle. The binding of the phycoerythrin-labeled IL-1 beta to the murine T cell line, EL-4, was examined as a positive control. The phycoerythrin-labeled IL-1 beta identified a specific IL-1 receptor in the EL-4 cells. Vascular smooth muscle cells were also positively stained by the fluorescent ligand. The binding of phycoerythrin-labeled IL-1 beta to these cells was saturable and reversed by 100-fold excess unlabeled IL-1 beta. Incubation of the vascular smooth muscle cells with IL-1 beta (25 ng/ml) or IL-6 (250 ng/ml) for 18 h increased and decreased, respectively, the percentage of cells positively stained by phycoerythrin-labeled IL-1 beta which suggests these cytokines regulate IL-1 receptor expression in these cells. These data indicate a specific receptor for IL-1 exists in vascular smooth muscle cells.

HIV infection and i.v. drug use: medical examiner cases in Essex and Hudson Counties, New Jersey.

Patterns of HIV infection and IV drug use in 697 Essex and Hudson Counties, New Jersey, 1986-1987 Medical Examiner (ME) cases, aged 15-59 years, were examined. All cases had toxicology tests for drugs and had been autopsied. Postmortem stored sera were blind-tested and confirmed for the presence of HIV-1-antibody by the New Jersey Department of Health. All cases and IV drug users were dichotomized according to the presence/absence of HIV-1-antibody and were then analyzed for differences in demographic and postmortem characteristics. Subjects were predominantly Black men aged 30-44 years; the 119 HIV(+) cases were even more likely to be Black or Hispanic and in the 30-44 age group. Evidence of IV drug use and HIV(+) status were very highly correlated; 86 of 181 IV drug users were HIV(+). There was a low rate of suicide among HIV(+) cases and IV drug users. Only 3 of 63 suicide victims were HIV(+), and they were the only IV drug users whose manner of death was certified as suicide. Cases with toxicology findings of both heroin and cocaine were most likely to be HIV(+), followed in order by those with heroin or cocaine alone present. Cocaine alone was the illicit drug most often present in toxicology tests on all cases. Among IV drug users, heroin with cocaine was most often present.

Characterization of cell selectivity of two novel inhibitors of nitric oxide synthesis.

We have assessed the capacity of two novel inhibitors to block cytokine-induced nitric oxide (NO) synthesis by macrophages and vascular smooth muscle cells, as well as NO production by the constitutive enzyme in central nervous system tissue. NG-Cyclopropyl-L-arginine selectively inhibited Ca2+/calmodulin-dependent NO synthesis, with an IC50 of 0.55 microM in brain versus 184 and 258 microM in macrophages and vascular smooth muscle cells, respectively. In contrast, NG-amino-L-homoarginine blocked NO production by all of the cell types examined, with IC50 values ranging from 6.6 to 26 microM. Both inhibitors were active in an in vivo model of endotoxic shock.

The effects of combining sanctions and rehabilitation for driving under the influence: an evaluation of the New Jersey Alcohol Countermeasures Program.

In contrast to many other state Driving under the Influence (DUI) programs developed in the United States in the 1970s as alternatives to traditional sanctions, the New Jersey Alcohol Countermeasures Program combined sanctions with mandatory education/rehabilitation for offenders. Three components were evaluated: DUI education, "treatment," and Alcoholics Anonymous. For 2,734 first and repeat offenders participating in this program between 1979 and 1982, the program was effective in reducing DUI recidivism for program completers (66% while licensed and 51% while suspended) compared with noncompleters, but it was less effective in reducing subsequent moving violations while licensed (20% compared with noncompleters) and accidents while licensed (18% compared with noncompleters). Completers had higher rates of violations and accidents while suspended (9% compared with noncompleters). A small group of repeat offenders, missassigned to DUI education, had higher post conviction rates of negative driving events than those of comparable offenders assigned to "treatment" or Alcoholics Anonymous, indicating that for these offenders the latter interventions were more effective.