Hepatitis C patients' self-reported adherence to treatment with pegylated interferon and ribavirin.

BACKGROUND: Prior research on adherence to hepatitis C treatment has documented rates of dose reductions and early treatment discontinuation, but little is known about patients' dose-taking adherence. AIMS: To assess the prevalence of missed doses of pegylated interferon and ribavirin and examine the correlates of dose-taking adherence in clinic settings. METHODS: One hundred and eighty patients on treatment for hepatitis C (23% coinfected with HIV) completed a cross-sectional survey at the site of their hepatitis C care. RESULTS: Seven per cent of patients reported missing at least one injection of pegylated interferon in the last 4 weeks and 21% reported missing at least one dose of ribavirin in the last 7 days. Dose-taking adherence was not associated with HCV viral load. CONCLUSIONS: Self-reported dose non-adherence to hepatitis C treatment occurs frequently. Further studies of dose non-adherence (assessed by method other than self-report) and its relationship to HCV virological outcome are warranted.

MEG-guided analysis of 7T-MRI in patients with epilepsy.

PURPOSE: To study possible detection of structural abnormalities on 7T MRI that were not detected on 3T MRI and estimate the added value of MEG-guidance. For abnormalities found, analysis of convergence between clinical, MEG and 7T MRI localization of suspected epileptogenic foci. METHODS: In adult patients with well-documented localization-related epilepsy in whom a previous 3T MRI did not demonstrate an epileptogenic lesion but MEG indicated a plausible epileptogenic focus, 7T MRI was performed. Based on semiologic data, visual analysis of the 7T images was performed as well as based on prior MEG results. Correlation with other data from the patient charts, for as far as these were available, was analysed. To establish the level of concordance between the three observers the generalized or Fleiss kappa was calculated. RESULTS: In 3/19 patients abnormalities that, based on semiology, could plausibly represent an epileptogenic lesion were detected using 7T MRI. In an additional 3/19 an abnormality was detected after MEG-guidance. However, in these later cases there was no concordance among the three observers with regard to the presence of a structural abnormality. In one of these three cases intracranial recording was performed, proving the possible abnormality on 7T MRI to be the epileptogenic focus. CONCLUSIONS: In 32% of patients 7T MRI showed abnormalities that could indicate an epileptogenic lesion whereas previous 3T MRI did not, especially when visual inspection was guided by the presence of focal interictal MEG abnormalities.

Suppression of a P450 hydroxylase gene in plant trichome glands enhances natural-product-based aphid resistance.

Trichome glands on the surface of many higher plants produce and secrete exudates affecting insects, microbes, and herbivores. Metabolic engineering of gland exudation has potential for improving pest/disease resistance, and for facilitating molecular farming. We identified a cytochrome P450 hydroxylase gene specific to the trichome gland and used both antisense and sense co-suppression strategies to investigate its function. P450-suppressed transgenic tobacco plants showed a > or =41% decrease in the predominant exudate component, cembratriene-diol (CBT-diol), and a > or =19-fold increase in its precursor, cembratriene-ol (CBT-ol). Thus, the level of CBT-ol was raised from 0.2 to > or =4.3% of leaf dry weight. Exudate from antisense-expressing plants had higher aphidicidal activity, and transgenic plants with exudate containing high concentrations of CBT-ol showed greatly diminished aphid colonization responses. Our results demonstrate the feasibility of significantly modifying the natural-product chemical composition and aphid-interactive properties of gland exudates using metabolic engineering. The results also have implications for molecular farming.

Membrane-bound ATPase of intact vacuoles and tonoplasts isolated from mature plant tissue.

Intact vacuoles were isolated from petals of Hippeastrum and Tulipa (Wagner G.J. and Siegelman, H.W. (1975) Science 190, 1298--1299). The ATPase activity of fresh vacuole suspensions was found to be 2--3 times that of protoplasts from the same tissue. 70--80% of the ATPase activity of intact vacuoles was recovered in tonoplast preparations. The antibiotic Dio-9 at 6mug/10(6) vacuoles or protoplasts causes 40% inhibition. However, only the protoplast ATPase is sensitive to oligomycin. N,N'-dicyclohexylcarbodiimide (DCCD) slightly stimulates ATPase activity in both vacuole and protoplast suspensions, whereas ethyl-3-(3-dimethylaminopropyl carbodiimide) (EDAC) strongly inhibits. Spectrophotometric studies show that in the petal the vacuolar contents have a pH of 4.0 for Tuplipa and 4.3 for Hippeastrum, whereas the intact isolated vacuole has an internal pH of 7.0 (in pH 8.0 buffer) for (Tulipa and about 7.3 for Hippeastrum. Internal ion concentrations of 150, 46, 30, 30 and 6 mM were found for K+, Na+, Mg2+, Cl-, and Ca2+ respectively, which are about the same as those in protoplasts.

A double-blind, placebo-controlled trial of testosterone therapy for HIV-positive men with hypogonadal symptoms.

BACKGROUND: The goal was to evaluate the efficacy of testosterone in alleviation of hypogonadal symptoms (diminished libido, depressed mood, low energy, and depleted muscle mass) in men with symptomatic human immunodeficiency virus illness. METHODS: Seventy-four patients were enrolled in a double-blind, placebo-controlled 6-week trial with bi-weekly testosterone injections, followed by 12 weeks of open-label maintenance treatment. Major outcome measures were Clinical Global Impressions Scale ratings for libido, mood, energy, and erectile function; Hamilton Depression Rating Scale scores, and Chalder Fatigue Scale scores. Body composition changes were assessed with bioelectric impedance analysis. RESULTS: Seventy men completed the 6-week trial. Response rates, defined as much or very much improved libido, were 74% (28/38) for patients randomized to testosterone, and 19% (6/32) for placebo-treated patients (P<.001). Of the 62 completers with fatigue at baseline, 59% (20/34) receiving testosterone and 25% (7/28) receiving placebo reported improved energy (P<.01). Among the 26 completers with an Axis I depressive disorder at baseline, 58% of the testosterone-treated patients reported improved mood compared with 14% of placebo-treated patients (Fisher exact test = .08). With testosterone treatment, average increase in muscle mass over 12 weeks was 1.6 kg for the whole group, and 2.2 kg for the 14 men with wasting at baseline. Improvement on all parameters was maintained during subsequent open-label treatment for up to 18 weeks. CONCLUSION: Testosterone is well tolerated and effective in the short-term treatment of symptoms of clinical hypogonadism in men with symptomatic human immunodeficiency virus illness, restoring libido and energy, alleviating depressed mood, and increasing muscle mass.

Fluoxetine treatment for depression in patients with HIV and AIDS: a randomized, placebo-controlled trial.

OBJECTIVE: The goals of this study were to determine whether fluoxetine is superior to placebo in treating HIV-seropositive patients with major depression or dysthymia or both, whether severity of immunosuppression is associated with treatment response, and whether fluoxetine treatment is associated with change in immune status as measured by CD4 cell count. METHOD: A double-blind, randomized, placebo-controlled 8-week trial of fluoxetine was conducted in a university-affiliated research outpatient clinic. The fluoxetine-placebo randomization was 2:1. All patients were offered 4 months of additional open treatment. Main outcome measures included the Clinical Global Impression, Hamilton Depression Rating Scale, and CD4 cell count. RESULTS: Of 120 patients randomly assigned to fluoxetine or placebo, 87 completed 8 weeks of treatment. In the total group, 51% had AIDS. All but three were men, 35% were nonwhite, and 6% had intravenous drug use as a risk factor. In an intention-to-treat analysis, 57% of fluoxetine patients and 41% of placebo patients were responders. Among patients who completed the study, 74% responded to fluoxetine and 47% to placebo; this difference was statistically significant. Severity of immunosuppression was not related to antidepressant response, attrition, or side effects, and fluoxetine treatment was not associated with change in CD4 cell count. CONCLUSIONS: Fluoxetine is an effective antidepressant in the context of HIV illness. However, both placebo response and attrition were substantial, suggesting both that nonspecific factors may be more salient and that yet another medication (i.e., an antidepressant) may be less acceptable among patients with serious medical illness already requiring multiple concomitant medications.

DHEA treatment for HIV+ patients: effects on mood, androgenic and anabolic parameters.

The goal of this pilot study was to evaluate the effect of dehydroepiandrosterone (DHEA) on depressed mood and fatigue in HIV+ men and women, unselected for baseline DHEA level. Secondary questions concerned treatment effects on libido and body cell mass, on serum testosterone levels, and elicitation of short-term side effects. Treatment consisted of an open-label 8-week trial using DHEA doses from 200 to 500 mg/day. Mood responders were maintained for another 4 weeks, then randomized to a double blind placebo controlled 4-week discontinuation trial. Forty-five patients, including six women, entered the trial. Of 32 week 8 completers, mood was much improved in 72%, and 81% were rated responders with respect to fatigue. Response on either parameter was unrelated to baseline serum DHEA level. Twenty-one patients entered the double blind discontinuation phase. No differences in relapse rate between placebo and DHEA groups were observed for either mood or fatigue. Body cell mass increased significantly by week 8, and this improvement was maintained throughout the double blind phase for patients in both treatment conditions. Libido increased significantly as well. DHEA therapy did not have an effect on CD4 cell count or on serum testosterone levels in men. In conclusion, DHEA may be a promising treatment for HIV+ patients with depressed mood and fatigue, although persistence of response even in placebo-treated patients during the discontinuation phase leaves unresolved questions. A parallel group double blind clinical trial is indicated as the next step to more clearly identify therapeutic efficacy.

Effects of dextroamphetamine on depression and fatigue in men with HIV: a double-blind, placebo-controlled trial.

BACKGROUND: This report documents findings from a small placebo-controlled trial of dextroamphetamine for depression and fatigue in men with the human immunodeficiency virus (HIV). Dextroamphetamine offers the potential for rapid onset of effect and activation properties, both of which are important to persons with medical illness and an uncertain, but limited, life expectancy. METHOD: Primary inclusion criteria included the presence of a DSM-IV depressive disorder, debilitating fatigue, and no history of dependence on stimulants. The study consisted of a 2-week randomized, placebo-controlled trial, with the blind maintained until week 8 for responders, followed by open treatment through the completion of 6 months. RESULTS: Of 23 men who entered the study, 22 completed the 2-week trial. Intent-to-treat analysis indicated that 73% of patients (8/11) randomly assigned to dextroamphetamine reported significant improvement in mood and energy, compared with 25% (3/12) among placebo patients (Fisher exact test, p < .05). Both clinician- and self-administered measures indicated significantly improved mood, energy, and quality of life among patients taking dextroamphetamine. There was no evidence of the development of tolerance of, abuse of, or dependence on the medication. CONCLUSION: These results suggest that dextroamphetamine is a potentially effective, fast-acting antidepressant treatment for HIV patients with depression and debilitating fatigue.

Sexual activity among HIV-seropositive gay men seeking treatment for depression.

BACKGROUND: With no cure or vaccine for AIDS expected in the near future, researchers have tried to locate predictors of high-risk sexual activity and develop interventions that emphasize primary prevention and encouragement of safe sex. This study examines the roles of depression, feelings of hopelessness, relationship status, and illness stage in mediating sexual activity among 85 HIV-seropositive (HIV+) gay men seeking psychiatric treatment for clinical depression. METHOD: Subjects were participants in a randomized, double-blind, placebo trial of imipramine. A self-report was used to assess sexual activity during the month prior to each assessment. RESULTS: Before and after initiation of treatment, a substantial proportion of these men were sexually abstinent and the vast majority of those who were sexually active denied practicing unprotected anal intercourse. Sexual abstinence was found to be associated with feelings of hopelessness (t = 2.8, p < .01), diagnosis of AIDS (chi 2 = 11.3, p < .01), and lower CD4 count (t = -2.6, p = .01). CONCLUSION: The sexual activity of this sample was characterized by caution or abstinence rather than promiscuity and recklessness. Severity and alleviation of depression were not associated with sexual abstinence. The possible ramifications of sexual abstinence on the mental health and quality of life of HIV+ gay men are briefly discussed.

Testosterone as a treatment for fatigue in HIV+ men.

This study assessed correlates of fatigue and the efficacy of testosterone therapy as a treatment for fatigue in men with symptomatic HIV and clinical hypogonadism. We conducted a 12-week open trial of testosterone for HIV+ men with clinical hypogonadism (low libido plus at least one of the associated symptoms of depressed mood, fatigue, and weight loss), CD4 count below 400 cells/cu.mm, and serum testosterone level below 500 ng/dl. 108 men entered the trial; 50% were nonwhite and 72% had an AIDS diagnosis. Baseline correlates of fatigue, as measured by the self-report Chalder Fatigue Scale (CFS), included elevated laboratory values (hematocrit, hemoglobin), lower overall physical functioning, greater psychological distress, and reduced quality of life. Sixty-six of 72 men who presented with fatigue completed the trial, with 52 (79%) rated as responders (much improved energy level) by the study doctor. Fatigue declined significantly among responders, but not nonresponders.

Dextroamphetamine as a treatment for depression and low energy in AIDS patients: a pilot study.

This report documents findings from an open trial of dextroamphetamine in the treatment of depression and low energy in AIDS patients. Dextroamphetamine offers the potential for rapid onset of effect and activation properties, both of which are important to persons with late stage HIV illness. Primary inclusion criteria included having a DSM-III-R depressive disorder, debilitating low energy, CD4 cell count below 200 cells/mm3, and no history of drug dependence. The trial consisted of open treatment in a 6-week protocol, with indefinite follow-up. Twenty-four men entered the study, 18 of 19 (95%) patients who completed at least 6 weeks of treatment reported substantial improvement with regard to both mood and energy at a median dosage of 10 mg/day. These results suggest that dextroamphetamine is a potentially effective, fast acting antidepressant treatment for this population and call for a larger, controlled trial.

Psychological and physical health correlates of body cell mass depletion among HIV+ men.

OBJECTIVE: To assess whether significant body cell mass depletion related to HIV is associated with declines in physical health and psychological well-being. METHODS: As part of a 2-year prospective HIV study, semiannual assessments included measures of body composition, psychological status, and physical health. RESULTS: As measured by bioelectric impedance analysis, 58 (31%) of 187 enrolled HIV+ men had significant body cell mass depletion at some point during the study, of who 23 subsequently lost at least an additional 5% of body cell mass in the 6 months between any two consecutive study visits. This additional body cell mass depletion was associated with significant increase in fatigue, global distress and depressive symptomatology, and reduced life satisfaction. CONCLUSION: These data illuminate the importance of monitoring body weight and body cell mass, and the need for awareness of the association between malnutrition, mental health, and quality of life.

"Extramarital" sex: is there an increased risk for HIV transmission? A study of male couples of mixed HIV status.

This report describes the sexual behavior with "extramarital" partners of men who are in committed relationships with men of opposite HIV status. We examined the rates of unprotected anal sex with outside partners and compared these rates with the prevalence of such activity within the couple, during the year prior to the assessment. Seventy-five couples were interviewed, of whom 50 (67%) reported sex outside of the primary relationship by one or both members of the couple. Rates of unprotected anal sex with one-night stands and "other" partners were 25% and 33%, respectively among men who engaged in anal sex with such partners. In contrast, 54% of the men who engaged in anal sex with their primary partner did not always use condoms. Data from men who engaged in anal sex with both their primary partner and one-night stand(s) revealed that condoms were used less frequently within the primary relationship when the HIV negative men were the insertive partner; otherwise the rates of unprotected anal sex were similar. Approximately 75% of HIV negative men who engaged in receptive anal sex always used condoms, and a similar proportion of HIV positive men always used condoms during insertive anal sex, regardless of partner type. The vast majority of unprotected anal sex occurred without ejaculation inside the rectum. Unprotected oral sex was highly prevalent regardless of partner type. Implications for public health policy and primary prevention research are discussed.

Testosterone therapy for clinical symptoms of hypogonadism in eugonadal men with AIDS.

We conducted a small exploratory study to assess whether testosterone therapy is an effective treatment for clinical symptoms characteristic of hypogonadism in eugonadal men with AIDS. Treatment consisted of 12 weeks of bi-weekly intramuscular injections of testosterone cypionate. Twenty-three men enrolled in the study; mean age was 37 and 44% were ethnic minorities. All had an AIDS diagnosis and the mean CD4 cell count was 150 cells/mm3. All baseline serum testosterone levels were within the laboratory reference range and above 500 ng/dl. Diminished libido was an inclusion criterion, plus each patient had at least one additional symptom (low mood, low energy, loss of appetite and/or weight). Nineteen men completed the trial and a majority of patients responded with regard to libido (89%), mood (67%), energy (71%), and appetite (67%) as rated by the Clinical Global Impressions Scale. With the exception of appetite, self and clinician rated measures showed significant improvement in all symptom domains. Among the 14 study completers with significant weight loss, the average weight gain was 2.3 kg, with a 1.8 kg increase in body cell mass and no change in body fat. These results suggest that testosterone is as effective in treating these symptoms in eugonadal men with AIDS as we have found in our research with hypogonadal HIV+men.

Testosterone treatment of clinical hypogonadism in patients with HIV/AIDS.

The use of testosterone to treat clinical symptoms of hypogonadism and wasting among patients with HIV/AIDS is a relatively new area of inquiry and clinical application. Outcome measures have included changes in mood, libido, energy, weight and muscle mass. The purpose of this review is to identify the questions most commonly raised about risks of testosterone therapy, to review available data which address these questions, and to discuss issues of clinical management. These include treatment indications, measurement issues, and side effects and their management.

Ethnic differences in response to fluoxetine in a controlled trial with depressed HIV-positive patients.

This study examined ethnic differences in response to antidepressant treatment. One hundred eighteen depressed HIV-positive patients entered an eight-week controlled trial of fluoxetine. Nineteen percent were black and 14 percent were Latino; the remaining two-thirds were white. Attrition was greater among Latinos than either blacks or whites. Black patients were more likely than whites to be nonresponders to fluoxetine. Latinos were more likely to respond to placebo compared with blacks and whites. Ethnic groups did not differ in the presence of treatment-emergent side effects.

Prevalence of extradyadic sex in male couples of mixed HIV status and its relationship to psychological distress and relationship quality.

This study assessed the prevalence of extradyadic sex and the relationship between such activity and psychological distress and relationship quality in male couples of mixed HIV serostatus. Sixty-three couples were interviewed and had sufficient data for inclusion in all analyses. With regard to sexual activity during the year prior to being interviewed, 19 (30%) couples were monogamous, 18 (29%) described themselves as "open," 13 (21%) kept extradyadic sex a secret from their partners, and in 13 couples there was only partial knowledge of extradyadic sex. Though not statistically significant, monogamous and open couples consistently scored lower numerically on measures of psychological distress and higher on measures of relationship quality, compared to "partial knowledge" and "secretive" couples. When pooled, monogamous and open couples scored significantly higher on measures of dyadic consensus, affectional expression, dyadic satisfaction, and sexual satisfaction compared to the combined subgroup of partial knowledge and secretive couples.

[Male pairs with mixed states of HIV]. / Parejas de hombres con estado mixto de VIH.

AIDS: The AIDS epidemic makes intimate relations difficult. Fear of sexual transmission is particularly evident in couples with one HIV-positive partner. The HIV Center for Clinical and Behavioral Studies initiated a project to assist mixed HIV-positive couples with their relationships and sexual relations. The participating couples ranged in age from 26 to 64 years. Their time together varied from four months to several years and the amount of sexual activity and degree of protection varied from couple to couple. The majority had oral sex without condoms and anal sex with condoms. Reasons given for not using condoms included: less pleasure, quality of sex is more important than safety, the HIV-negative partner feels little risk, condoms are a reminder of AIDS, etc. The necessity for safe sexual relations proved problematic in many couples. The AIDS-infected person can lose interest in sexual relations or feel unattractive due to the progressive nature of the illness. The pair is further affected by the proximity of death, as some may distance themselves emotionally to protect their mate. At the end of the group sessions, it was clear that the majority of the couples benefitted from the experience. Phone numbers and contacts for mixed HIV-positive couples interested in participating in the project are given.^ieng