Dissociation of experimentally induced drinking behavior by ibotenate injection into the median preoptic nucleus.

Adult male Sprague-Dawley rats were injected with either ibotenic acid (5 micrograms/1 microliter) or vehicle in the ventral median preoptic nucleus. The injections were given during either methoxyflurane or ketamine anesthesia. None of the rats injected with ibotenic acid were adipsic after surgery. After at least one week of recovery, all rats were tested for drinking responses to angiotensin II (1.5 and 3 mg/kg s.c.) and hypertonic saline (3% and 12% 1 ml/100 g b.wt.). Rats injected with ibotenic acid during methoxyflurane anesthesia drank significantly less than the vehicle injected control group in tests with both doses of angiotensin II and both concentrations of hypertonic saline. The rats that were injected with ibotenic acid during ketamine anesthesia drank significantly less than the control group when tested with 3% hypertonic saline but not when tested with angiotensin II. Histological examination of the injection sites indicated significant reductions in the volume of the median preoptic nucleus only in rats that had been injected with ibotenic acid during methoxyflurane anesthesia. The results are consistent with the interpretation that the drinking response to angiotensin II is dependent upon the integrity of neurons with postsynaptic N-methyl-D-aspartate receptors within the median preoptic nucleus.

Effects of chronic marijuana use on testosterone, luteinizing hormone, follicle stimulating hormone, prolactin and cortisol in men and women.

To investigate possible effects of chronic marijuana use on reproductive and stress hormones, we assayed testosterone, luteinizing hormone, follicle stimulating hormone, prolactin, and cortisol in 93 men and 56 women with a mean (+/- S.E.) age of 23.5 +/- 0.4 years. Hormone values were compared among groups of subjects stratified according to frequency of marijuana use (frequent, moderate and infrequent; N = 27, 18, and 30, respectively) and non-using controls (N = 74). Chronic marijuana use showed no significant effect on hormone concentrations in either men or women.

Acute effects of marijuana on cognition: relationships to chronic effects and smoking techniques.

A double-blind, placebo-controlled study assessed acute effects on human cognition of marijuana smoking involving long or short durations of inhalation and breath holding. During eight test sessions, 48 adult, male volunteers completed standardized, pencil-and-paper tests of educational development and ability, as well as computerized tests of learning, associative processes, abstraction, and psychomotor performance. Marijuana impaired all capabilities except abstraction and vocabulary. These impairments were more pervasive than those associated with heavy, chronic marijuana use in a previous study involving the same tests, but showed some similarities. Marijuana altered associative processes, encouraging more uncommon associations. Marijuana-induced impairment in learning pairs of words was influenced by associative relationships between the words. There were a few hints that prolonged breath holding increased marijuana's effects under some test conditions, but in general it did not. Prolonged breath holding itself affected performance in four tests, regardless of whether subjects smoked marijuana or placebo. Whether physiological or psychological factors (e.g., exposure to carbon monoxide in smoke or subjects' expectations) produced these effects could not be determined.

Sedative, stimulant, and other subjective effects of marijuana: relationships to smoking techniques.

A double-blind, placebo-controlled study assessed subjective effects of smoking marijuana with either a long or short breath-holding duration. During eight test sessions, 55 male volunteers made repeated ratings of subjective "high," sedation, and stimulation, as well as rating their perceptions of motivation and performance on cognitive tests. The major finding of the study was that the long, relative to the short, breath-holding duration increased "high" ratings after smoking marijuana, but not placebo. Marijuana smoking increased sedation and a perception of worsened test performance, and decreased motivation with respect to test performance. Paradoxical subjective effects were observed in that subjects reported some stimulation as well as sedation after smoking marijuana, particularly with the long breath-holding duration. Breath-holding duration did not produce any subjective effects that were independent of the drug treatment, i.e.. occurred equally after smoking of marijuana and placebo, such as we previously observed with respect to test performance.

Improving the quality of care of patients with asthma: the example of patients with severely symptomatic disease.

The increasing economic burden of asthma care is incurred partly by patients with more severe symptoms. However, little is known about the characteristics of these severe asthma patients. This study examined sociodemographic, disease-specific characteristics and health care utilization that are related to asthma disease severity, for the purpose of identifying areas for treatment improvement. A total of 2927 asthma patients (12 years or older), who were continuously enrolled in one of three participating health plans for a 6-month study period and who responded to an asthma survey, were included in the study. Univariate and multivariate analyses were performed to examine the sociodemographic, disease-specific characteristics and health care utilization by asthma severity. About 25% of the patients reported experiencing severe asthma symptoms. They were more likely to be African-Americans, Hispanics, women, patients with less than a college education, residents in the south-west, current smokers, and those receiving care from non-specialists. Severe asthmatics reported having less of an understanding of the clinical manifestation of asthma and the means to manage asthma exacerbation. Outpatient contacts did not differ significantly between severe and other patients, although their utilization of emergency room and inpatient care was significantly greater. This study suggests that a significant proportion of asthma patients is experiencing severe symptoms and barriers other than access to care prevent appropriate control of asthma. Poor control appears to be related to smoking, deficits in knowledge about self-care, not receiving medical care from a specialist, and inadequate use of medications.

Methylphenidate improves HIV-1-associated cognitive slowing.

Sixteen HIV-1 seropositive individuals participated in a single-blind, placebo-controlled, crossover-design study of the effectiveness of 30 mg/ day of methylphenidate (MPH) in the treatment of HIV-associated cognitive slowing. Regression analyses revealed that participants who entered the study with a greater degree of either depressive symptomatology or cognitive slowing tended to demonstrate a better response to MPH on computerized measures of choice and dual-task reaction time. Participants without evidence of cognitive slowing at study entry did not show greater improvement on MPH than on placebo. Contrary to expectation, symptoms of depression did not respond better to MPH than to placebo, regardless of initial symptomatology. Information processing slowing in HIV-1 infection therefore appears amenable to pharmacologic intervention with the dopamine agonist MPH. However, results suggest clinicians should consider reserving the use of MPH for patients with more pronounced cognitive and affective deficits.

Verbal working memory in HIV-seropositive drug users.

Recent evidence suggests that HIV-seropositive drug users are impaired on tasks of visuospatial working memory compared with drug users seronegative for HIV. In the current study we evaluated the performance of 30 HIV-seropositive male drug users and 30 risk-matched seronegative controls on two measures of verbal working memory, the Listening Span and the verbal Self Ordered Pointing Task. Impaired working memory performance was significantly more common among HIV-seropositive persons compared to controls, with the highest incidence of deficit among symptomatic participants. These findings indicate that working memory deficits in persons with HIV are not domain-specific and can be demonstrated reliably in drug users.