Biomedical subjects
N Hartman
Publications and source records attributed to N Hartman.
Transdermal nicotine and smoking behavior in psychiatric patients.
The authors used a double-blind crossover design to observe the effect of transdermally administered nicotine on the smoking behavior of 13 psychiatric patients who were not trying to stop smoking. The patients smoked significantly fewer cigarettes while receiving nicotine than while receiving placebo. These data suggest that transdermally administered nicotine can be a useful adjunct in treating nicotine-addicted psychiatric patients in a non-smoking environment.
Long-term toxicity/activity profile of 2',3'-dideoxyinosine in AIDS or AIDS-related complex.
To evaluate the long-term toxicity and activity profile of 2',3'-dideoxyinosine (ddI), a potent inhibitor of human immunodeficiency virus (HIV) replication, in vitro. 58 patients with AIDS or AIDS-related complex were studied with additional reference to the effect of previous treatment with zidovudine, and the effect of ddI on HIV-induced cognitive dysfunction. Doses above 9.6 mg/kg per day of ddI were frequently associated with toxicity (peripheral neuropathy, pancreatitis, or hepatitis). Doses of 9.6 mg/kg per day or below were well tolerated for up to 21 months. A subset of patients receiving 3.2-9.6 mg/kg per day of ddI had long-term immunological improvement and reduction of serum HIV p24 antigen. Immunological changes were especially seen in patients who had little previous zidovudine therapy. 5 patients with HIV-induced cognitive impairment improved with ddI. Thus, ddI may have anti-HIV activity at doses which are tolerated for long-term therapy, although pancreatitis could be a life-threatening complication.
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.
Metyrapone-induced withdrawal symptoms: symptoms in methadone-maintained patients.
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Reduction of cigarette smoking by use of a nicotine patch.
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3,5,3'-triiodothyroacetic acid therapy for thyroid hormone resistance.
3,5,3'-Triiodothyroacetic Acid (Triac) is reputed to suppress pituitary secretion of TSH with minimal metabolic effects. Triac has been used successfully to treat eight patients with thyroid hormone resistance. We gave Triac to a woman with selective pituitary resistance for treatment of hyperthyroidism (patient 1) and to a man with generalized resistance and chronic schizophrenia to determine whether it would improve his schizophrenia (patient 2). Patient 1 was given 0.35-3.5 mg Triac/day; patient 2 was given 0.7-4.2 mg/day. Dosages were increased by 0.7 mg/day every 2 weeks. Serum T3, T4, free T4, TSH, TSH response to TRH, systolic time intervals (STI), angiotensin-converting enzyme (ACE), and lipids were monitored bimonthly. In both patients, there was no change in symptoms, weight, lipids, or STI. In patient 1, basal TSH suppressed from 16.3 to 1.5 mU/L; in patient 2, from 2.0 to 0.5 mU/L. The peak TSH response to TRH stimulation decreased from 144 to 12.5 mU/L in patient 1 and from 14.2 to 2.8 mU/L in patient 2. Serum T4 decreased from 160 to 109 nmol/L in patient 1 and from 270 to 192 nmol/L in patient 2. ACE levels were persistently elevated in both patients. Resting energy expenditure, measured by oxygen consumption, was increased by Triac in both patients (12% in patient 1 and 9% in patient 2). Although Triac suppressed TSH and T4 secretion in both patients, it did not reduce peripheral action of thyroid hormone as expressed in STI, resting energy expenditure, and ACE. We conclude that in these two patients with resistance to thyroid hormone, at the doses used to suppress TSH and T4 secretion, the intrinsic peripheral action of Triac offset whatever decrease in thyroid hormone secretion it produced.
Relation between clinical features of the mitral prolapse syndrome and echocardiographically documented mitral valve prolapse.
Mitral valve prolapse, the most common inherited cardiovascular condition, has been associated with a variety of signs, symptoms and electrocardiographic abnormalities, but the true spectrum of the mitral prolapse syndrome remains in doubt because clinical findings often contribute to patient identification and their prevalence in patient groups may be overstated because of ascertainment bias. Accordingly, clinical findings in 88 patients with echocardiographic mitral prolapse were compared with those in 81 of their adult first degree relatives with mitral prolapse (a group free of ascertainment bias) and in two control groups without mitral prolapse: 172 first degree relatives and 60 spouses. Comparison of relatives with and without mitral prolapse demonstrated true associations between mitral prolapse and clicks or murmurs, or both (67 versus 9%, p less than 0.001), thoracic bony abnormalities (41 versus 16%, p less than 0.001), systolic blood pressure less than 120 mm Hg (53 versus 31%, p less than 0.001), body weight 90% or less of ideal (31 versus 14%, p less than 0.005) and palpitation (40 versus 24%, p less than 0.01). In contrast, relatives with mitral prolapse showed no significant increase over normal relatives or spouses without mitral prolapse in prevalence of chest pain, dyspnea, panic attacks, high anxiety or repolarization abnormalities, but these features were all more common in women than in men (p less than 0.01 to less than 0.001). Thus, the true spectrum of the mitral prolapse syndrome encompasses a midsystolic click and late systolic murmur, thoracic bony abnormalities, low body weight and blood pressure and palpitation. Other suggested clinical features, including nonanginal chest pain, dyspnea, panic attacks and electrocardiographic abnormalities, have appeared to be associated with mitral valve prolapse because of ascertainment bias and an erroneous classification of differences between men and women as being due to mitral valve prolapse.
Effect of methadone plus neuroleptics on treatment-resistant chronic paranoid schizophrenia.
In a placebo-controlled single-crossover study, seven patients with treatment-resistant chronic paranoid schizophrenia who received methadone plus neuroleptic showed significant improvement. Methadone may be a useful adjunctive treatment in a subpopulation of patients with chronic paranoid schizophrenia.
ACTH, cortisol and beta-endorphin response to metyrapone testing during chronic methadone maintenance treatment in humans.
Normal responses to metyrapone were observed in most steady-state methadone maintained treatment patients. These preliminary studies suggest that in recently detoxified methadone maintained treatment patients, there may be an exaggerated response of the hypothalamic-pituitary-adrenal axis to metyrapone.
Circadian rhythms and levels of beta-endorphin, ACTH, and cortisol during chronic methadone maintenance treatment in humans.
Previous studies have shown alterations of neuroendocrine function in humans receiving any narcotic on short-term basis or short-acting narcotics on a chronic basis. In this study of 16 well-stabilized patients, it was demonstrated that normalization of hypothalamic-pituitary-adrenal axis function, as reflected by normal levels and normal circadian rhythm of levels of beta-endorphin, ACTH and cortisol, is achieved during long-term steady state methadone maintenance treatment of former heroin addicts.
Alcohol use in youthful methadone-maintained former heroin addicts: liver impairment and treatment outcome.
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Chronic use of opioids and antipsychotic drugs: side effects, effects on endogenous opioids, and toxicity.
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Change in Ig expression of a human lymphoblastoid line during long-term culture.
A human lymphoblastoid line, in continuous culture for over 3 years, showed changes in Ig expression with time. The following pattern of events was suggested by studies of Ig synthesis and secretion performed at intervals. In a mass culture containing a heterogeneous cell population, Ig expression may shift because of selection acting on the different phenotypes. In human lymphoblastoid lines there may be a tendency for selection to favor IgMchi-producing cells. In clones, including those that synthesize multiple H chains, substantial determinism for Ig expression is present.
A glycoprotein associated with the membrane fraction of human B but not T lymphocytes.
A method is described which employs differential centrifugation and sucrose density gradient centrifugation to isolate a membrane fraction from human lymphocytes. Membrane preparations from long-term human cultured B- and T-lymphoid lines, peripheral blood lymphocytes, tonsillar lymphocytes, and thymocytes were analyzed on 0.5% sodium dodecyl sulfate-7.5% polyacrylamide gels stained for protein and carbohydrate. The most important finding was a major glycoprotein of approximately 30,000 daltons associated with the membrane preparations from B lymphocytes. T-lymphocyte preparations did not contain readily detectable amounts of this membrane-associated component. The T-cell lymphoid line MOLT-4 was unique in that it had a narrow protein band at approximately 30,000 daltons which did not contain carbohydrate.
Restriction endonuclease B and f1 heteroduplex DNA.
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An f1 mutant with reduced sensitivity to P1 restriction.
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