Cyclosporin A protects striatal neurons in vitro and in vivo from 3-nitropropionic acid toxicity.

The neuroprotective properties of cyclosporin A (CsA) are mediated by its ability to prevent mitochondrial permeability transition during exposure to high levels of calcium or oxidative stress. By using the mitochondrial toxin 3-nitropropionic acid (3NP), the present study assessed whether CsA could protect striatal neurons in vitro and in vivo. In vitro, 3NP produced a 20-30% reduction of striatal glutamic acid decarboxylase-immunoreactive (GAD-ir) neurons. A single treatment with CsA protected GAD-ir neurons from 3NP toxicity at lower (0.2 or 1.0 microM), but not at higher (5.0 microM) doses. Similar findings were seen when the cultures were treated twice with cyclosporin. In vivo experiments used the Lewis rat model of Huntington's disease (HD) in which a low 3NP dose was delivered subcutaneously through an osmotic minipump. Rats received unilateral or bilateral intrastriatal saline injections to disrupt the blood-brain barrier (BBB) and facilitate CsA reaching vulnerable neurons. In the first experiment, CsA treated 3NP-lesioned rats displayed significantly more dopamine-and adenosine-3;, 5;-monophosphate-regulated phosphoprotein (DARPP32-ir) neurons ipsilateral to BBB disruption compared to the contralateral intact striatum, indicating that disruption of the BBB maybe necessary for CsA's neuroprotective effects. In the second experiment, stereological counts of DARPP32-ir neurons revealed that CsA protected striatal neurons in a dose-dependent manner following bilateral disruption of the striatal BBB. Rats treated with the higher (15 or 20 mg/kg) but not lower (5 mg/kg) doses of CsA displayed greater numbers of DARRP32-ir striatal neurons relative to vehicle-treated 3NP-lesioned rats. Thus, under conditions in which CsA can gain access to striatal neurons, significant protection from 3NP toxicity is observed. Therefore, CsA or more lipophilic analogues of this compound, may be of potential therapeutic benefit by protecting vulnerable neurons from the primary pathological event observed in HD.

Preemployment drug screening in a large metropolitan medical center: a one-month trial.

To assess the prevalence of illicit drug use among job applicants, a large metropolitan medical center conducted preemployment drug screening of all applicants during January 1988. Urine samples from 172 preinformed applicants were screened using Enzyme Multiplied Immunoassay Technique (Emit d.a.u.) followed by confirmatory gas chromatography/mass spectrophotometry. 4.1% of tests were positive for marijuana and/or cocaine and none was positive for heroin. Positive findings increased with decreasing socioeconomic status. The findings suggest that applicants for jobs in large medical centers in metropolitan areas are no different from those in other sectors of the economy with respect to illicit drug use.

Epidemiologic findings on a swine farm with enzootic toxoplasmosis.

A farm in Illinois had swine with enzootic Toxoplasma gondii infections. Ninety-five of 99 pigs had antibody against T gondii by the modified agglutination test; modified agglutination test titers were less than 1:10 (4 pigs), 1:10 (15 pigs), 1:20 (12 pigs), 1:40 (10 pigs), 1:80 (20 pigs), 1:160 (11 pigs), 1:320 (12 pigs), 1:640 (9 pigs), and greater than or equal to 1:1,280 (6 pigs). To trace the route of infection, Toxoplasma-free pigs were introduced into the farm and were evaluated serologically at various intervals. Analysis of data derived from these tracer pigs indicated that cannibalism was a major source of T gondii infection in the pigs.

Field evaluation of the enzyme-linked immunosorbent assay for swine trichinosis: efficacy of the excretory-secretory antigen.

A field evaluation of an enzyme-linked immunosorbent assay (ELISA) for swine trichinosis was done with sera obtained from 5 herds experiencing ongoing transmission of Trichinella spiralis. Epizootiologic studies conducted on these herds offered an opportunity to evaluate the accuracy of an ELISA, using larval T spiralis excretory-secretory antigens. Sera from 162 infected pigs and 143 serum samples from noninfected pigs originating from the same farms were tested. The infection status of the pigs was determined by digestion of diaphragm or tongue muscle samples. Two criteria were established to classify the ELISA optical density (OD) readings: Criterion I stated that an OD greater than or equal to 5 times the mean OD of several normal swine sera pools was positive; criterion II stated that a OD greater than or equal to 4 times the normal sera values was positive. The results obtained did not reveal obvious serologic variations among infected herds located in the 4 states involved. Overall, the test detected 93% (criterion I) and 96% (criterion II) of infected pigs. The majority of false-negative sera was from hogs that had less than 5 larvae/g of muscle; 1 hog had 73.8 larvae/g of diaphragm muscle. The false-positive rates were 8% for criterion I and 9% for criterion II. The actual rate for these false-positive samples may have been overestimated, because generally, only small tissue samples (0.4 to 10 g) were digested; larger sample sizes might have altered the results. The relevance of this qualification is that these pigs originated from herds with prevalence rates greater than 50%. Other factors that may account for occasional false-positive sera or false-negative sera in the swine trichinosis ELISA are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Trichinosis in a herd of swine: cannibalism as a major mode of transmission.

In a herd of approximately 1,000 hogs, evaluation of muscle specimens collected at various intervals during a 12-year period (1973 to 1985) indicated continuous transmission of Trichinella spiralis. The farm's rat population and the incidence of trichinosis in the rats was high during 1974, but diminished markedly by 1978. In January 1984, a longitudinal investigation, using tracer pigs, was performed to determine whether rodents and/or other wild animals were involved in transmission of T spiralis on this farm. Tracer pigs exposed to rodents and wild animals did not become infected with T spiralis. The rodent population on the farm was small and none of the rodents trapped and examined were found to be infected. Hog cannibalism also was evaluated as a mode of T spiralis transmission. Results of the investigation indicated that hog cannibalism was the mode of transmission for trichinosis in the herd.

Cocaine use in persons on methadone maintenance.

Although cocaine use had increased dramatically among all levels of society over the past several years, its use by heroin addicts has existed for decades. To determine whether the prevalence or the pattern of cocaine use changes once an addict enrolls in methadone maintenance, a survey of cocaine use among persons in methadone maintenance therapy was conducted. Of the 613 persons surveyed, 229 (37%) chose to participate, with 33 (14%) considered invalid because of incomplete responses. Of the remaining 196 (86% of the participants), 64 (33%) indicated no cocaine use prior to methadone maintenance, and 132 (67%) reported some prior use. Once treatment had begun, 9 (14%) with no history of prior use admitted to at least one event within the last 6 months, and 55 (86%) reported no use. Of those reporting use prior to methadone maintenance, 41 (31%) stopped usage and 91 (69%) continued. Of the total participants, approximately half used cocaine at least once during methadone maintenance. Among those who used cocaine before and during methadone maintenance, the predominant route of administration was parenteral, 72 (54%) and 46 (51%) participants, respectively. It should be noted that there was a net gain of 17% of patients who stopped using cocaine as a result of entering methadone maintenance. Indices of cocaine use by random urinalysis over the preceding 6 months, for the entire clinic population, revealed only 86 (14%) to 110 (18%) patients to have urine samples positive for cocaine. Although cocaine use decreased on methadone maintenance, its use is still considerable, with the pattern of use differing from the recreational cocaine use in a non-narcotic-dependent population. Random urinalysis for cocaine appears to be an insensitive indication of prevalence of use.

Loitering by patients on methadone maintenance: a perception or a problem.

Loitering has become an increasing matter of concern to both communities and staff involved in drug treatment programs. In order to determine the prevalence of this problem a retrospective two-year study was performed among clients enrolled in a community methadone maintenance treatment program (MM). Of 1064 persons enrolled in MM during this time, 190 (17.8%) were identified as loiterers with 121 (63.7%) loiterers actively enrolled in MM. No significant differences between loiterers and a matched group of MM clients were seen with respect to time in treatment, presence of drug abuse or excessive alcohol intake. Differences between loiterers and non-loiterers were observed with respect to criminal activity (29% vs. 11%, respectively, P less than 0.001), non-opioid drug abuse (78% vs. 67%, respectively, P less than 0.01) and productive activity (44% vs. 61%, respectively, P less than 0.01). Excessive alcohol intake was seen in 15.4% of the study group. No relationship existed between excessive consumption of alcohol and loitering, arrests, and use of mood altering drugs as determined by urinalysis. No relationship could be demonstrated between loitering and residence in the community surrounding the program. Only 11 (6%) of all loiterers lived within two blocks of the program boundaries, and only 59 (31%) resided within East Harlem. These findings suggest that loitering is a real cause for concern being engaged in mainly by individuals who are neither socially productive nor residents of the immediate community surrounding the program. It is therefore important to develop strategies for dealing with this problem not only to reassure the community but to facilitate rehabilitation.

Is treatment for alcoholism effective in persons on methadone maintenance?

A randomized prospective study of 625 drug addicts on methadone maintenance revealed that 105 (17%) were active alcoholics, 47 (8%) were inactive alcoholics, and 473 (76%) were not alcoholics. The active alcoholics were randomly assigned to abstinence therapy, controlled drinking with behavior modification, or a control group receiving the usual clinic services. There were no differences between treatment and control groups at baseline and during follow-up of up to 2 1/2 years, and there was no relation between remission and treatment, suggesting that the effectiveness of currently employed specific interventions for alcoholism in active alcoholic addicts maintained on methadone cannot be demonstrated.

Alcoholism among narcotic addicts and patients on methadone maintenance.

There was no difference in prevalence of current alcoholism between new admissions to a methadone-maintenance treatment program (MMTP) and patients already in MMTP at least one year, by previous treatment for drug misuse, or between MMTP patients and the population of the surrounding community.

Alcoholism as a risk factor in methadone maintenance. A randomized controlled trial.

A randomized controlled trial of 625 addicts on methadone maintenance identified 105 (17 percent) as active alcoholics, 47 (8 percent) as inactive alcoholics, and 473 (75 percent) as nonalcoholics. Subjects were followed for up to 29 months (mean 53.7 weeks) to assess the influence of alcoholism on the rehabilitative process. During the study, alcohol consumption significantly decreased (p less than 0.001) in active alcoholics. Indexes of productive activity on entry or during follow-up revealed no significant differences between active alcoholics and other patients with the exception of alcohol-related hospitalizations (p less than 0.001). Behavioral indexes consistently improved with treatment in all patients, being greatest among active alcoholics (p less than 0.01). During the study, 28 (7 percent) of 399 nonalcoholics were recategorized as active alcoholics, and remission from alcoholism was noted in 28 (27 percent) of patients who were initially classified as alcoholic. These findings suggest that alcoholism does not significantly affect rehabilitation from narcotic use and therefore should not be cause for detoxification from methadone maintenance.

Alcohol consumption in persons on methadone maintenance therapy.

Alcohol use among methadone maintenance treatment program (MMTP) patients is substantial and a frequent impression is that addicts accelerate their consumption once in MMTP. This study reports an attempt to more clearly define alcohol consumption in opioid dependence as well as changes associated with methadone maintenance therapy. Two-day alcohol consumption (2-day EtOH) data were collected initially and quarterly on participants in a randomized controlled trial of intervention for alcoholism. Blood alcohol levels (BAL) were also determined. 17% of the participants were classified as active alcoholics (AA) and 8% as inactive alcoholics (IA). Two-day EtOH and BAL were significantly higher for AA than AI and nonalcoholics (NA, and AI higher than NA. Two-day EtOH decreased significantly over time for AA, AI, and NA. These findings indicate that AA among narcotic addicts and those on MMTP consume large quantities of EtOH but that consumption decreases with time on MMTP. The results, in confirmation of the work of others, suggest that entry and participation in MMTP has a broader effect than just on the use of narcotic drugs.

The effect of alcoholism in methadone-maintained persons on productive activity: a randomized control trial.

The effect of alcoholism on indices of productive activity was determined in a prospective, randomized, and controlled study of alcoholism in narcotic addicts undergoing methadone maintenance (MM) therapy. Indices of productive activity included: percentage of persons engaged in productive activities; number of days worked per quarter; number of arrests per quarter; number of hospitalizations; and days of hospitalizations per quarter. Baseline as well as longitudinal data were obtained on operative alcoholics (OA), inactive alcoholics (IA), and nonalcoholics (NA). OA patients were subsequently randomized to a control group or groups receiving either abstinence-oriented insight group therapy or controlled drinking-oriented behavioral modification group therapy. The retention rate in MM of OA versus NA during the 29-month clinical phase of the study did not differ significantly. Similarly, no significance was reported with respect to any index of productive activity. Indices of productive activity in OA undergoing treatment as compared to those randomized to the control group also did not reveal any significant differences. The compliance of OA in seeking and maintaining therapy for their alcoholism, however, was sufficiently poor so that any conclusions concerning the effectiveness of therapy on indices of productive activity should be viewed cautiously.

The ability of a Self-Administered Alcohol Screening Test (mSAAST) to detect future excessive alcohol consumption in persons on methadone maintenance.

A modified Self-Administered Alcoholism Screening Test (mSAAST) was prospectively administered to 625 narcotic addicts participating in a randomized clinical control trial to study its effectiveness in detecting future excessive alcohol consumption. At entry into the study, of 105 patients categorized as active alcoholics, 84 (80%) obtained a positive score on the mSAAST. Of 77 patients initially identified as being at risk for developing alcoholism (potential alcoholics) by mSAAST scores, 31 (40%) subsequently developed characteristics of excessive alcohol consumption. Of the 321 patients classified as nonalcoholic by history as well as mSAAST score, a significantly lesser proportion (15%) developed characteristics of excessive alcohol consumption (p less than 0.001). These findings suggest the mSAAST to be a useful adjunctive indicator of persons at risk of developing excessive consumption of alcohol. It is probable that the usefulness of the mSAAST extends beyond narcotic-dependent populations and may be of value in identifying the potential for excessive alcohol consumption in other populations.

Abuse of amitriptyline.

Amitriptyline hydrocholride (Elavil) is frequently used in treating mild to moderate depressive states. A survey of 346 persons enrolled in a methadone maintenance program showed that 86 (25%) had admitted taking amitriptyline with the purpose of achieving euphoria. Thin-layer chromatography of random urine specimens over five months showed that 34% of the patients had a positive result for amitriptyline at least once during this time. These results suggest that misuse of amitriptyline is not uncommon and should be carefully considered prior to prescribing this agent to narcotic dependent persons.

Adequacy of sexual performance in men maintained on methadone.

Impairment of sexual performance may occur in men on methadone maintenance. A random sample of 50 of 355 men enrolled in a methadone program was interviewed with respect ot sexual activity. Seventeen (33%) reported sexual dysfunction, occurring in 50% within 1 month after initiating methadone therapy. A comparison between these individuals and those without a reported change in sexual activity revealed no differences with respect to demographic parameters, methadone dose, or presence of polydrug abuse. Inadequate sexual function on heroin, however, was reported in 12 (71%) of those experiencing similar difficulties on methadone. This finding was present in only one person (3%) of those individuals whose sexual function on methadone maintenance was considered adequate. This study suggests that those persons with altered sexual function while on street heroin represent a high risk group for the development of inadequate sexual function upon initiation of methadone maintenance.