Plasma testosterone in narcotic addiction

Mean plasma testosterone levels in male heroin addicts, meth adone-maintained, former methadone-maintained and abstinent addicts did not differ significantly from that of normal controls. A prospective study before and during 1 year of methadone maintenance treatment showed no change in the mean plasma testosterone levels during treatment; no correlation was observed between plasma testosterone levels and symptoms of sexual disturbances. Some untreated heroin addicts and some methadone-maintained patients had plasma testosterone values below the lower limits of normal. In the methadone-treated group there was no direct methadone dose-testosterone level relationship, although patients receiving 40 mg of methadone or less had significantly higher mean testosterone levels than those receiving more than 40 mg of methadone daily. There was no relationship between serum glutamic oxaloacetic trans-aminase (SGOT), presence or absence of illicit drug use, or plasma luteinizing hormone level and plasma testosterone. A significant relationship between low testosterone levels and recognized alcoholism was evident.     

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 < 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 < 0.001). Behavioral indexes consistently improved with treatment in all patients, being greatest among active alcoholics (p < 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.     

The effect of heroin and multiple drug abuse on the electrocardiogram

The electrocardiograms (ECG) of 75 asymptomatic individuals admitted to a methadone treatment program were analyzed to determine the effect of street heroin and other drugs of abuse. All patients were free of cardiac, renal, or pulmonary disease and had no laboratory abnormalities. Two groups of patients were studied. In Group I there were 34 patients on heroin only which was taken within 24 hours of the ECG. Abnormalities were noted in 55 per cent; QT_c prolongation was found in 19 per cent, and significant bradyarrhythmias were found in 19 per cent. In Group II there were 41 patients on methadone with multiple drug abuse; changes were found in 66 per cent. QT_c prolongation was noted in 34 per cent, prominent U waves in 32 per cent, and bradyarrhythmias were found in 32 per cent.It is now a well-known fact that the sudden death syndrome in addicts may not be a pharmacologic or dosage-related phenomenon. The existence of conduction, depolarization, and repolarization abnormalities, as well as bradyarrhythmias in a significant number of drug-dependent individuals may play a role in the production and facilitation of lethal arrhythmias and may be the mechanism of the acute fatal reaction.     

Alcohol Use in Youthful Methadone-Maintained Former Heroin Addicts: Liver Impairment and Treatment Outcome

Combined alcohol abuse and narcotic dependency is now recognized as a common problem in adults but has not been well characterized in adolescents, nor have the effects of combined substance abuse on liver function in this age group been assessed. Forty-four youthful former heroin addicts (27 males (M) and 17 females (F)) on methadone maintenance therapy were interviewed in detail about past and present alcohol use and underwent physical examination. Liver function studies and tests for hepatitis B antigen and antibody were performed. Four and onehalf years later, 28 of these patients still in treatment or willing to return for study purposes were similarly reevaluated. The original sample included 15 whose alcohol intake was high (12 M + 3 F: group A) and 29 whose intake was low or absent (15 M + 14 F: group N). Sixty-six per cent of group A patients and 58% of group N patients remained in treatment at the second time point. Group A had significantly greater abnormalities in liver function than group N with evidence of progression over 4 1/2 years, based both on physical examination and blood chemistry results. Seventy-five per cent of the patients had evidence of exposure to hepatitis B virus (anti HB. positive) in 1981 while 7% demonstrated antigenemia. The results demonstrate that: (1) alcohol abuse is common among adolescents and young adults in methadone maintenance therapy; (2) that it is associated with significant acute or chronic liver impairment; (3) exposure to HE virus is endemic in youthful former heroin addicts; and (4) the retention of alcohol-abusing patients in methadone treatment and drug-free follow-up is as great as with non-alcohol abusing patients.     

Abstinence following detoxification and methadone maintenance treatment

During an 11 year overview of methadone treatment, 161 (72 per cent) of 225 patients who completed detoxification were followed up to eight years. Fifty-one (22.6 per cent) of those were classified as stable and narcotic free 2.9 years after detoxification. Of 89 self-selected patients who had undergone a planned, supported, “therapeutic” detoxification, 37 (42 per cent) were classified narcotic-free; whereas many fewer were so judged after other methods of detoxification. Relapse to nonprescribed opioid use, detected in 34 (38.7 per cent) of those traced, was inversely related to time since detoxification. Relapse potential was very low after three years of apparent continuous narcotic-free existence; three years should be a minimal time for successful detoxification. Some subjects had several cycles of methadone treatment and detoxification. Most patients with combined alcohol-methadone dependencies did poorly, whether or not detoxification from opiolds was undertaken. Since the frequency of enduring narcotic-free state was only 9.7 per cent of 522 patients in the treatment sample, detoxification should not be a realistic goal for all patients who enter treatment.     

Correlation of low serum IgM levels with absence of functional splenic tissue in sickle cell disease syndromes

Serum immunoglobulin concentrations were determined in 21 patients with sickle cell disease syndromes and correlated with the size and visualization of the spleen. Whereas serum immunoglobulin A (IgA) levels were elevated in all patients studied, immunoglobulins G (IgG) and M (IgM) were elevated in those patients with demonstrable increase in splenic mass. When even minimal splenic visualization could be demonstrated, serum IgM was normal. However, when there was complete absence of splenic vi-sualization, or following splenectomy, serum IgM concentration was significantly below normal. This finding of low serum IgM concentration may explain the increased susceptibility to infection observed in some groups of patients with sickle cell disease.     

The Economics of Methadone Programs

The number of methadone programs in New York City has increased in recent years to a total of 161 treatment programs for ex-heroin addicts. Some of the economic implications of this are discussed. A follow-up study of 112 dropouts and 110 active patients of one of the largest methadone maintenance programs provides an opportunity to compare the sources of financial support for these persons. Of the dropouts who went to other programs, 78 per cent were on public assistance, and this is almost identical to the 79 per cent of active patients at the program sampled who were on public assistance. This is about twice as high as the proportion of drug-free dropouts who were on public assistance (38 per cent). Several interpretations are offered for these differences. The need for accurate monitoring and evaluation of drug-treatment facilities is emphasized because it is as important that the tax-payer not be short-changed as it is that the addict or ex-addict receives the kind of treatment that he or she needs to be able to lead a productive and autonomous life.     

Psychotherapy/counseling for opiate addicts: strategies for use in different treatment settings

The authors review evidence from outcome studies of psychotherapy for opiate addicts and make recommendations regarding the use of psychotherapy on the basis of the findings. The place of psychotherapy is evaluated for three types of treatment settings: outpatient drug-free treatment, narcotic antagonist treatment, and methadone maintenance. The heterogeneity of opiate addicts is emphasized, as is the need for multidimensional assessment of clients in order to maximize the effectiveness of psychotherapies offered. In each of the treatment settings evaluated, psychotherapy appears to be most promising for a subgroup of those seen. For outpatient drug-free treatment, psychotherapy appears to be most useful for the new client with no treatment history, the successful client graduating from a more intensive program, the client who has temporarily relapsed, and the client leaving jail or a hospital. In a narcotic antagonist program, psychotherapy appears to be most useful for clients entering the program from illicit heroin use and not for those switching from methadone maintenance to a narcotic antagonist program. Moreover, in the maintenance phase of the program, preliminary evidence suggests the value of family therapy for aiding treatment retention. Regarding psychotherapy in the context of a methadone maintenance program, it appears to be best reserved for those addicts who present to treatment with relatively severe levels of psychiatric symptoms.     

Feasibility of maintaining normal glucose profiles in insulin-dependent pregnant diabetic women

This study was designed to test the feasibility of a patient-monitored glucose determination program to establish and maintain normal blood glucose levels. Ten pregnant women, who were insulin-dependent diabetics prior to becoming pregnant and who were in their eighth week or less of pregnancy, were offered the program. All 10 accepted and continued the program for the duration of their pregnancy. Normal plasma glucose (60 to 140; x? = 80 mg/dl) levels were achieved after one week of the program and were maintained throughout the pregnancy as documented by 5 to 8 blood glucose determinations a day. The hemoglobin A_1c level, which was elevated in all 10 patients at the start (9.4 ± 1.6 per cent) of the program, fell into the normal range (2 to 5.0 per cent) five weeks after glucose values became normal. Serum estradiol (0.8 ± 0.6 ng/ml), serum prolactin (10 ± 9 ng/ml) and serum human chorionic gonadotropin (5,500 ± 1,700 ng/ml), although all abnormal at the start of the program, became normal after glucose control was achieved (program weeks 4, 5 and 6, respectively). The infants showed no signs of macrosomnia (2,988 ± 959 g), hypoglycemia, hyperbilirubinemia, hypocalcemia, erythremia or respiratory distress. Therefore, a program to maintain normal blood glucose levels during a diabetic patient's pregnancy is not only possible but may also improve the pregnancy and the outcome.     

Accidental hypothermia in an alcoholic population

Thirty-nine cases of accidental hypothermia are reviewed. Data indicate that mortality varies with the presence of underlying disease rather than with the degree of hypothermia or the methods of rewarming. In 31 patients with hypothermia alone (average temperature 85 °F) mortality was 6.25 per cent. In eight patients with hypothermia and another primary condition (average temperature 84 °F) mortality was 75 per cent.Intractable cardiac arrhythmia has been reported as the primary cause of death in hypothermia. In these patients, death during hypothermia resulted from pulmonary complications. Ventricular arrhythmias, when they occurred, were responsive to routine measures such as electrical cardioversion and myocardial suppressant drugs. Methods of treatment are discussed.     

Abnormal liver function tests as biological markers for alcoholism in narcotic addicts

Liver Function Test (LFT) abnormalities are frequently observed in narcotic addicts. However, the role of alcohol in producing such changes remains unclear. In order to evaluate the effects of alcohol in producing LFT elevations as well as the use of routine LFTs to serve as biochemical markers for alcoholism in narcotic addicts, 612 addicts participating in a randomized control trial of intervention in alcoholism were studied. Baseline parameters including LFTs and history of alcohol use were obtained on entry into the study and subsequently periodically during follow-up which varied from 6 months to 2 1/2 years (mean 13.5 months). On entry to the study, 104 of 612 (17%) of addicts were classified as alcoholics. Mean values of LFTs (SGOT, SGPT, Alkaline phosphatase, GGTP) in the alcoholic cohort were significantly increased compared to those among nonalcoholics (p less than 0.01 to less than 0.001 for individual tests). Mean values of LFTs did not significantly change during methadone maintenance in either group. Although a greater proportion of alcoholic addicts had elevated LFTs, the predictive values for each test (18 to 35%) were sufficiently low to prevent them from being used as biochemical markers of alcoholism. These findings suggest that although elevations in LFTs are frequently present in narcotic addicts and are significantly greater among addicts who are also alcoholic, most elevations are not specifically due to alcohol. Conventional LFTs are therefore of limited value in assessing alcoholism among narcotic addicts.     

Hepatobiliary diseases associated with serum antimitochondrial antibody (AMA)

In an attempt to define the clinical spectrum of hepatobiliary disease associated with antimitochondrial antibody (AMA), 41 female and four male patients with AMA were investigated. On the basis of clinical criteria, 22 patients had primary biliary cirrhosis (group I), seven had extrahepatic biliary obstruction (group II) and 16 had other liver diseases including chronic active hepatitis, cryptogenic cirrhosis and minor abnormalities of liver function (group III). Elevations of serum cholesterol, alkaline phosphatase and bile acid levels separated the patients with primary biliary cirrhosis from those with miscellaneous liver disease, whereas in those with extrahepatic biliary obstruction results were intermediate. The cholestatic syndrome of primary biliary cirrhosis was further defined by a cholic to chenodoxycholic acid ratio > 1.0 which was found in 75 per cent of the patients with primary biliary cirrhosis but in none of those with miscellaneous liver disease. No significant differences in AMA titers or immunoglobulin M (IgM) levels were found between the groups, indicating that these tests are not correlated with cholestatic liver disease. Examination of liver tissue revealed features which were compatible with the clinical impression in the majority of cases. Cholelithiasis was present in 33 per cent of the patients. Common bile duct obstruction due to stones and/or stricture was found in six cases and carcinoma in one. Since four had fully developed cirrhosis at the time of presentation, extrahepatic biliary obstruction was probably a result of gallstone disease complicating AMA positive parenchymal liver disease. AMA seems to be a marker for idiopathic parenchymal liver disease, primarily in middle-aged women, but in itself gives no. further diagnostic information and does not exclude extrahepatic biliary obstruction.     

Heroin nephropathy: A clinicopathologic and epidemiologic study

The existence of a nephropathy secondary to intravenous narcotic use remains a matter of debate. To determine whether heroin use and renal disease are associated, a clinicopathologic and epidemiologic study was undertaken in the Buffalo Standard Metropolitan Statistical Area (Buffalo-SMSA).Over the past 10 years, 23 addicts presented with the nephrotic syndrome and/or renal insufficiency. All patients were black men 18 to 45 years of age. Kidney biopsies performed on 21 patients uniformly showed sclerosing glomerulonephritis. End stage renal disease (ESRD) developed in 15 of these patients.In the epidemiologic evaluation which spanned four and a half years, heroin use was highly correlated with both sclerosing glomerulonephritis and ESRD. A history of intravenous heroin use was found in 26 per cent of the new cases of sclerosing glomerulonephritis and in 13 per cent of the new cases of ESRD in patients aged 18 to 45 years (p < 0.000001).This investigation confirms the existence of heroin-associated sclerosing glomerulonephritis in black men. Heroin use appears to be a major risk factor for ESRD in the Buffalo-SMSA.     

Ten Years of Methadone Maintenance Treatment: Some Clinical Observations

Ten years of methadone maintenance were reviewed in all 547 patients admitted to one clinic in New York City. High retention rates, reduced but still high mortality rates, increased employment, and minor degrees of recognized opiate abuse characterized those remaining in treatment. The treated patients appeared to evolve into a unique social and economic class, partly in the drug subculture and partly outside the drug world. Many were dependent on public assistance for living expenses, methadone treatment, and medical care. An interesting finding was their heavy demands for inpatient hospital care, often for drug-related reasons. A segment of New York City narcotic addicts was sequestered in an open-ended treatment process with considerable benefits to themselves and to society. Only a small fraction appeared to gravitate toward full economic support, to discontinuation of methadone, and to an enduring narcotic-free state.     

Ten years of methadone maintenance treatment: some clinical observations

Ten years of methadone maintenance were reviewed in all 547 patients admitted to one clinic in New York City. High retention rates, reduced but still high mortality rates, increased employment, and minor degrees of recognized opiate abuse characterized those remaining in treatment. The treated patients appeared to evolve into a unique social and economic class, partly in the drug subculture and partly outside the drug world. Many were dependent on public assistance for living expenses, methadone treatment, and medical care. An interesting finding was their heavy demands for inpatient hospital care, often for drug-related reasons. A segment of New York City narcotic addicts was sequestered in an open-ended treatment process with considerable benefits to themselves and to society. Only a small fraction appeared to gravitate toward full economic support, to discontinuation of methadone, and to an enduring narcotic-free state.     

A comparative study of ticarcillin plus tobramycin versus carbenicillin plus gentamicin for the treatment of serious infections due to gram-negative bacilli.

The combination of ticarcillin plus tobramycin (TT) or carbenicillin plus gentamicin (CG) was used to treat 82 patients with severe systemic gram-negative infection in a prospective, randomized study. Pseudomonas aeruginosa was the primary pathogen in 7 (93 per cent) of these patients. Patients treated with TT responded more frequently (92 per cent or 37 of 40) than patients treated with CG (71 per cent or 30 of 42) (p is less than 0.05). This difference was primarily due to a greater response to TT in patients with pulmonary infections (93 per cent versus 68 per cent) and infections due to Pseudomonas (92 per cent versus 70 per cent). Severity of underlying disease was also an important determinant of response. Except for a greater incidence of hepatotoxicity with CG (23 per cent versus 3 per cent; p is less than 0.02), there was no difference in toxicity, colonization with drug-resistant microorganisms or superinfection between the two treatment groups. The combination of TT appears to be superior to CG for the treatment of pulmonary infections due to Pseudomonas aeruginosa.     

The influence of prolonged stable methadone maintenance treatment on mortality and employment: an 8-year follow-up

A cohort of 169 opiate drug addicts was followed for 8 years. The mortality rate was 3.3 per year. The average lethality per observation year was found to be higher than in other studies. The treatment with methadone was unstable and only 11% had received stable prolonged maintenance treatment. It is not possible to reject a model that described increasing mortality rates neither as a function of falling methadone maintenance treatment nor as a function of socially unstable addicts contra stable addicts. Unemployment was high in the cohort (87%), and no relationship could be demonstrated between methadone maintenance treatment and employment.     

Metyrapone-induced withdrawal symptoms

The metyrapone test is widely used in endocrinological testing to assess the integrity of hypothalamic-pituitary-adrenal axis function; we have used it to study the metabolic basis of addictive disease and opioid dependence. In recent studies, we have observed that metyrapone administration in long-term methadone-maintained patients and in patients undergoing slow dose reduction to drug-free status following chronic treatment may induce a narcotic withdrawal-like syndrome. Although metyrapone is known to produce mild adverse reactions in non-opiate dependent subjects, narcotic withdrawal-like symptoms have not been previously observed or reported. The metyrapone test was administered to 15 former heroin addicts: 10 (8 male, 2 female) in steady-state methadone maintenance therapy (30 to 90 mg/d) and 5 (3 male, 2 female) in the final phase of a slow methadone dose reduction procedure (0 to 10 mg/d). Eight out of 15 methadone maintenance subjects exhibited a narcotic withdrawal-like syndrome ranging from ‘moderate’ to “severe’ and four additional subjects had‘mild’ symptoms, occurring within 1 h after metyrapone administration, and resolving within 2 h of onset. No significant symptoms were seen in 3 methadone maintained subjects nor in any of 9 normal volunteers (7 male, 2 female). The mechanism by which metyrapone induces symptoms resembling narcotic withdrawal in opiate-dependent individuals is unknown but physicians performing this test should be aware of this possible response.     

Treatment collaboration of methadone maintenance programs and therapeutic communities

Although they developed from different backgrounds, therapeutic communities and methadone maintenance programs became major treatments of heroin abuse in the 1970s. Research published in the last 5 years demonstrates that therapeutic communities are associated with long-lasting improvements in functioning for the few drug abusers who stay in treatment at least 3 months. A principal limitation of this modality is that few patients remain in treatment long enough to acquire the changed values that produce long-lasting effects. Research on methadone maintenance continues to show that this treatment produces immediate decreases in criminality and drug abuse; however, patients who taper off of maintenance are prone to relapse. The aspects of treatment that appear to prevent relapse include minimizing withdrawal symptoms during tapering and providing support during and after completing maintenance. The strengths of these two treatment modalities can be combined to enable narcotic addicts to taper off of methadone maintenance in a therapeutic community and remain drug-free. Several other clinical, administrative, and research collaborations could be beneficial, pooling the medical/technical expertise of maintenance programs with the intensity of therapeutic community treatment.