A double-blind, placebo-controlled pilot study to evaluate the efficacy and safety of oral nalmefene HCl for alcohol dependence.

A dozen studies have been published showing that opiate antagonists suppress alcohol drinking in animals, and two independent placebo-controlled, double-blind clinical trials of naltrexone found this agent was associated with decreased alcohol craving and consumption in alcohol-dependent patients. Nalmefene is a newer opiate antagonist that has a number of potential advantages over naltrexone in the treatment of alcoholism, including no dose-dependent association with liver toxicity and more effective binding to central opiate receptors. Consequently, a double-blind pilot study was conducted to gather preliminary data on the safety and efficacy of nalmefene for reducing alcohol consumption in alcohol-dependent subjects. Twenty-one alcohol-dependent subjects meeting admission criteria were randomly assigned to 12 weeks of double-blind treatment with 40 mg nalmefene, 10 mg nalmefene, or placebo, resulting in 7 patients/treatment group. Nalmefene was well tolerated, with no serious adverse drug reactions. The 40 mg group had a significantly lower rate of relapse (p < or = 0.05), and a greater increase in the number of abstinent days/week (p < or = 0.09), than the other treatment groups. A significant decrease in the number of drinks/drinking day was noted for both nalmefene groups (p < or = 0.04), but not for placebo. These results were supported by parallel decreases in ALT. These pilot data provide preliminary support for the hypotheses that nalmefene can be safely given to alcoholics, and that nalmefene may have a role in reducing alcohol consumption and preventing relapse, particularly at the 40 mg level. A full-scale study is underway to confirm these preliminary findings.

Impact of vitamin B6 status on psychological distress in a longitudinal study of HIV-1 infection.

OBJECTIVE: Inadequate vitamin B6 status has been associated with altered neuropsychiatric function, possibly through its effect on the metabolism of neurotransmitters, including serotonin (5-HT). The present eighteen month longitudinal study evaluated the relationship between vitamin B6 status and psychological distress in HIV-1 infected individuals, controlling for the influence of negative life events, social support and coping style. METHOD: Biochemical measurements of nutritional status, and dietary intake evaluations were obtained in HIV-1 seropositive homosexual men, (at baseline: CDC Stages II and III, n = 70; Stage IVA, IVC2 n = 18) at six month intervals. Alterations in nutrient status (e.g., vitamin B6 adequate to inadequate; inadequate to adequate), were compared with changes in psychological distress, measured by the Profile of Mood States, using a multiple regression analysis. RESULTS: A significant decline in psychological distress was demonstrated with normalization of vitamin B6 status from inadequate to adequate status (p < 0.02). A decrease in psychological distress was also observed with increased tryptophan intake in subjects who were vitamin B6 adequate (p < 0.02). CONCLUSIONS: Significant effects for the nutritional variables remained even when negative life event stressors, social support, and coping style were controlled, suggesting that vitamin B6 status may be an important co-factor in determining level of psychological distress over time in HIV-1 infected individuals.

The esterified plasma fatty acid profile is altered in early HIV-1 infection.

Previous studies have shown that alterations in micronutrient utilization occur in patients with Acquired Immune Deficiency Syndrome. In this study, total plasma fatty acid composition was measured in 36 homosexual men infected with the Human Immunodeficiency Virus 1 (HIV-1) and in 17 HIV-1 seronegative homosexual men in order to evaluate differences associated with early HIV-1 infection. Immunologic assessment included CD4 cell number count and lymphocyte blastogenesis in response to the mitogens phytohemagglutinin (PHA) and pokeweed (PWM). The mean total amount of omega 6 polyunsaturated fatty acids (18:2 and 20:4) was significantly lower in the HIV-1 seropositive subjects (38 +/- 8.1% SD) as compared to HIV-1 seronegative subjects (43 +/- 4.2%; P = 0.0027). This was also reflected in a higher level of total saturated fatty acids (16:0 and 18:0) in HIV-1 seropositive subjects (30 +/- 2.2% vs. 26 +/- 2.8%; P = 0.0001). The ratio of linoleic to arachidonic acid (18:2 to 20:4) was higher in the HIV-1 seropositive group (6.76 +/- 4.88) compared to the HIV-1 seronegative group (4.86 +/- 1.37; P = 0.0213). The response to PHA in seropositive subjects correlated inversely with total plasma omega 6 fatty acids (r = -0.36; P = 0.027), and directly with the 18:2 to 20:4 ratio (r = 0.33; P = 0.046). CD4 cell counts and the response to PWM did not correlate with plasma fatty acid levels in HIV-1 seropositive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Active coping style is associated with natural killer cell cytotoxicity in asymptomatic HIV-1 seropositive homosexual men.

The aim of this study was to examine the hypothesis that a psychosocial model was associated with natural killer cell cytotoxicity (NKCC) in HIV-1 infection. A sample of 62 HIV-1 seropositive homosexual men at CDC stages II and III were given a psychosocial battery assessing life stressors, social support, and coping style. A regression model quantifying these variables along with control variables for alcohol use, substance use and nutritional status was estimated. Active coping style was directly and positively associated with NKCC, and trends toward a negative relationship of life stressors and a buffering effect of social support on lives stressors were also observed. The results suggest that (1) control variables should be included with psychosocial models and that (2) psychosocial factors, especially active coping, may have a deterrent effect on loss of NK cell function. Active coping style may merit a specific focus in future research of life stressors and the immune system.

Nutritional status of institutionalized elderly in south Florida.

To assess the nutritional status of an elderly nursing home population of South Florida, forty-seven persons with ages ranging from 65 to 96 years were studied. Complete clinical examination and anthropometric measures were performed, along with blood cell count, biochemical blood parameters and assessment of water-soluble vitamins levels. The most common clinical finding were edentulous (67%), general pallor (44%), hyperpigmentation (33%), dry skin (26%) and arcus corneitis (26%). Thirty-five percent of the studied population had cholesterol levels greater than 220 mg/dl. Triglyceride levels were also significantly elevated in a considerable subset of our subjects, with 30% having levels above threshold value of 150 mg/dl. Small proportions of subjects showed low levels of albumin (6%), total protein (28%), ascorbic acid (2%), and thiamin (9%). Forty-five percent of males were pyridoxine deficient, while 63% of the females presented such deficiency. This study underscores the need to define, with greater precision, the nutritional status of aged populations as well as improve our inadequate standards associated with the "normal" aging process. Nutritional intervention--only possible when appropriate standards are defined--can potentially serve not only to prevent the occurrence of significant morbidity and mortality, but can also be employed to enhance quality of life in the elderly individuals.

Specific nutrient abnormalities in asymptomatic HIV-1 infection.

OBJECTIVE: To determine whether specific nutrient abnormalities occur in earlier stages of HIV-1 infection, thereby preceding the marked wasting and malnutrition that accompany later stages of the infection. DESIGN: A longitudinal investigation to determine biological, psychological and social factors thought to influence the progression and outcome of HIV-1 infection. Nutritional status was assessed using biochemical measurement of nutrient levels, dietary history, anthropometry and clinical examination for the signs and symptoms of nutritional deficiency or excess. SETTING: The study was performed on an outpatient basis at the University of Miami School of Medicine. PARTICIPANTS: One hundred homosexual men, aged between 20 and 55 years, who were asymptomatic other than persistent generalized lymphadenopathy (Centers for Disease Control stage III) and 42 age-matched homosexual men demonstrated to be free of HIV-1 infection at two 6-month intervals. MAIN OUTCOME MEASURES: Biochemical measurement of nutrient status, dietary history, anthropometry, clinical signs or symptoms of nutritional excess or deficiency were obtained for all participants. RESULTS: Despite few differences in mean blood levels of specific nutrients, prevalence of specific nutrient abnormalities was widespread among HIV-1-infected subjects, compared with non-infected male homosexual controls. Overtly and marginally low blood levels of vitamins A (18%), E (27%), riboflavin (26%), B6 (53%), and B12 (23%), together with copper (74%) and zinc (50%) were documented in HIV-1-seropositive subjects. With the exception of riboflavin, zinc, and copper, a similar prevalence of abnormalities among HIV-1-seronegative controls was not observed. CONCLUSION: Specific nutrient abnormalities occur with relative frequency in asymptomatic HIV-1 infection and may contribute to the rate and form of HIV-1 disease progression.

Plasma vitamin B12 level as a potential cofactor in studies of human immunodeficiency virus type 1-related cognitive changes.

Studies of cognitive function in subjects with human immunodeficiency virus type 1 (HIV-1) infection who remain relatively asymptomatic (ie, Centers for Disease Control stages II and III) have provided widely variable estimates of cognitive impairment. In view of the finding that approximately 25% of asymptomatic HIV-1-infected subjects demonstrate either marginal or overt vitamin B12 deficiency, we have investigated plasma vitamin B12 status as a potential cofactor in studies of HIV-1-related cognitive impairment. When cognition was assessed in asymptomatic (Centers for Disease Control stages II and III) HIV-1-infected participants taking into consideration vitamin B12 status, those subjects with low plasma vitamin B12 levels (less than 180 pmol/L) performed more poorly than did those with normal (greater than or equal to 180 pmol/L) vitamin B12 status on specific measures of information processing speed and visuospatial problem-solving skills. These findings suggest that concurrent vitamin B12 deficiency may be a cofactor in subtle cognitive changes observed in the asymptomatic stages of HIV-1 infection. These differences in prevalence of low plasma vitamin B12 levels may help to explain differences among studies in the proportion of HIV-1-infected subjects showing cognitive impairment.

Cocaethylene: a unique cocaine metabolite displays high affinity for the dopamine transporter.

Concurrent cocaine and alcohol use is common practice in the general population, as indicated by recent prevalence studies. In the presence of ethyl alcohol, cocaine is metabolized to its ethyl homolog, cocaethylene. The transesterification of cocaine and ethanol to cocaethylene takes place in the liver and represents a novel metabolic reaction. Cocaethylene was detected in postmortem blood, liver, and neurological tissues in concentrations equal to and sometimes exceeding those of cocaine. In vitro binding studies demonstrate that cocaethylene has a pharmacological profile similar but not identical to that of cocaine at monoamine transport sites assayed in the human brain. Cocaethylene was equipotent to cocaine at inhibiting [3H]mazindol binding to the dopamine transporter. The blockade of dopamine reuptake in the synaptic cleft by cocaethylene may account for the enhanced euphoria associated with combined alcohol and cocaine abuse.

Zidovudine-associated adverse reactions in a longitudinal study of asymptomatic HIV-1-infected homosexual males.

Chemotherapeutic regimens frequently interact with and may influence nutritional factors. To determine the possible effects of zidovudine (ZDV) treatment on nutrient status, this study examined and compared the nutritional, immunological, and hematological status of asymptomatic, CDC stage III, HIV-1-seropositive males (n = 15) provided with ZDV (500-1,200 mg/day) and 22 nontreated, CD4-matched HIV-1-seropositive subjects. Prior to ZDV administration, hematological and plasma nutrient levels were similar in both groups. Following ZDV treatment, drug-treated subjects demonstrated alterations in hematological and nutritional parameters. A large proportion of the ZDV-treated participants exhibited decreased levels of zinc and copper along with a significant increase in red cell folate. The level of plasma zinc appeared to be particularly important in maintaining immune function in the ZDV-treated group. Whereas ZDV-treated subjects with adequate zinc levels displayed a significant increase in the response of peripheral blood lymphocytes to mitogens, this enhancement was not demonstrated in zinc-deficient, ZDV-treated participants or in untreated individuals whose lymphocyte response significantly declined over time, despite adeqaute zinc status. The findings of this study reveal a zidovudine-induced effect on nutritional parameters, indicating the importance of monitoring nutritional status with drug therapeutic regimens.

Association of vitamin B6 status with parameters of immune function in early HIV-1 infection.

Nutritional deficiencies have been documented to affect immune function. The present study indicates that vitamin B6 deficiency is prevalent in CDC stage III HIV-1-infected subjects, despite adequate dietary vitamin B6 intake. As vitamin B6 deficiency has been previously shown to affect immune function, these relatively asymptomatic HIV-1-infected patients were examined for evidence of a relationship between vitamin B6 deficiency and immune dysregulation. Vitamin B6 status in HIV-1-infected subjects was significantly associated with functional parameters of immunity [multivariate F(3,36) = 3.70, p less than or equal to 0.02]. Additional analyses indicated that overtly deficient participants exhibited significantly decreased lymphocyte responsiveness to the mitogens phytohemagglutinin and pokeweed, and reduced natural killer cell cytotoxicity, compared to subjects with clearly adequate vitamin B6 status (chi 2 = 8.78, df = 3, p less than 0.04). Vitamin B6 status was not related to immune cell subpopulations, e.g., CD4, CD8 cell number, or level of serum immunoglobulins. The results of this study indicate that while vitamin B6 status is not a primary etiological factor in HIV-1-related immunological dysregulation, it appears to be an important cofactor of immune function.

Use of an expanded-whole-wheat product in the reduction of body weight and serum lipids in obese females.

To achieve weight reduction and alter serum lipid profiles, an air-expanded whole-wheat protein product (SNW) was used by moderately obese women as a meal substitute for 12 wk. Results were compared with those from a standard low-calorie diet (LCD). The SNW group lost 3.9 kg (means) over the first 6 wk and a further 1.6 kg between weeks 6 and 12. In contrast, the LCD group lost 2.8 kg during the initial 6 wk but failed to achieve weight loss during the second 6 wk. Consequently, the SNW group lost nearly twice as much weight over the 12-wk period as did LCD participants. A beneficial effect of SNW on serum cholesterol and triglycerides was noted; both measures declined in conjunction with the weight loss. Such alterations were greater in the SNW group than in LCD participants. Both schemes proved safe. SNW is safe and effective in weight reduction and serum lipid modification in moderately obese women.