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Biomedical subjects

Igor Grant

Publications and source records attributed to Igor Grant.

At least 91 records · Page 5Linked to original sources

The 50 and 100-item short forms of the Paced Auditory Serial Addition Task (PASAT): demographically corrected norms and comparisons with the full PASAT in normal and clinical samples.

While the standard 200-item version of the Paced Auditory Serial Addition Task (PASAT) is a sensitive neuropsychological instrument, it can be quite aversive to some patients due to its length and progressively increasing difficulty. We present demographically-corrected norms for 50 and 100-item short-form versions in a sample of 560 neurologically normal adults. Age, education, and ethnicity (but not gender) were found to be significant predictors of performance. In a clinical sample of 786 HIV-infected adults, diagnostic accuracy of the 50, 100, and 200-item versions was essentially equivalent (using clinical ratings of a comprehensive neuropsychological battery as the gold standard, overall classification rates of the three PASAT versions were 71%, 74%, and 73%, respectively), with better specificity (89-92%) than sensitivity (46-53%). The 50-item version showed moderate ceiling effects, but the 100-item test did not. In a mixed clinical sample of 40 subjects, the 50-item version was administered more than twice as fast as the 200-item version, and was tolerated better (discomfort rating of 4.0 vs. 5.9 on a 10-point scale, p < .05). We conclude that in many cases the PASAT-50 and PASAT-100 provide equivalent diagnostic accuracy with a significant reduction in administration time and patient discomfort.

Adult↗

Effects of alcoholism and gender on brain metabolism.

OBJECTIVE: Proton magnetic resonance spectroscopy was used to evaluate gender influences on alcohol-associated changes in brain metabolism. METHOD: Concentrations of N-acetylaspartate, choline-containing compounds, myo-inositol, and creatine plus phosphocreatine in frontal lobe gray matter and white matter were estimated in eight women and 17 men who were recently detoxified from long-term alcoholism. Twelve women and 13 men with no history of alcoholism were used as a comparison group. RESULTS: In male and female alcoholics, frontal lobe white matter concentrations of N-acetylaspartate were significantly lower (-8.8%) than those seen in nonalcoholic comparison subjects. In the frontal lobe gray matter region, a significant alcoholism status-by-gender interaction and follow-up analyses revealed that female alcoholics had significantly lower N-acetylaspartate concentrations (-10.73%) relative to female comparison subjects, while male alcoholics and male comparison subjects had similar levels of this metabolite (<1% difference). CONCLUSIONS: Lower concentrations of white matter N-acetylaspartate, which may indicate neuronal loss or dysfunction, is equally severe in men and women with comparable alcohol abuse histories. However, female alcoholics exhibited significantly less N-acetylaspartate in frontal gray matter relative to female nonalcoholic comparison subjects, which could mean that female alcoholics are more susceptible to gray matter injury than their male counterparts. However, this finding could also be explained by higher-than-expected levels of N-acetylaspartate in the healthy female comparison group.

Adult↗

Acute procoagulant stress response as a dynamic measure of allostatic load in Alzheimer caregivers.

Allostasis designates processes of bodily adaptation to stressful challenges, whereas allostatic load means the costs of wear and tear to the body as a consequence of inefficient allostasis. In distressed dementia caregivers, an acute procoagulant stress response might be one dynamic mediator of allostatic load relevant to cardiovascular endpoints. An interviewer assessed the number of negative life-events independent from caregiving over 4 weeks in 37 spousal Alzheimer caregivers (M age +/- SD = 72 +/- 6 years). Baseline procoagulability scores and procoagulability scores in response to a 15-min speech task included plasma thrombin/antithrombin III complex, D-dimer, von Willebrand factor, tissue-type plasminogen activator, and plasminogen activator inhibitor 1 levels. Allostatic load was defined as the difference in procoagulability scores from baseline to speech, using standardized (z-score) transformations. Speech stress significantly increased heart rate (p =.017), systolic blood pressure (p =.002), and diastolic blood pressure (p <.001). The number of negative life-events (M +/- SD 2.8 +/- 2.0) correlated with allostatic load (r =.367, p =.026). After controlling for age and smoking, which together explained 32% of the variance in the allostatic load (R2 =.324), F(2, 34) = 8.14, p =.001, the number of negative life-events accounted for an additional 13% of that variance (Delta R2=.125), Delta F(1, 33) = 7.49, p =.010. The finding is compatible with the concept of allostasis and allostatic load, suggesting that higher combined caregiving and life distress levels are associated with more dysfunctional hemostatic responses to acute mental stress. The acute procoagulant stress response might constitute a dynamic mediator of allostatic load in Alzheimer caregivers.

Adaptation, Physiological↗

Binge use of methamphetamine among HIV-positive men who have sex with men: pilot data and HIV prevention implications.

This study compared the social and behavioral characteristics of binge users and nonbinge users of methamphetamine (meth) in a sample of 90 HIV-positive men who have sex with men. Forty-one participants (46%) self-identified as a binge user. Meth binges ranged from 2 to 33 days (mean = 5.6), and average consumption was 3.1 grams. Binge users were significantly more likely than nonbinge users to be ethnic minority and to have lower education. The two groups did not differ in terms of the total amount of meth used in the past 30 days; however, binge users reported significantly more social difficulties, more mental and physical health problems, and more sexual risk behaviors as compared with nonbinge users. The findings are discussed in relation to drug treatment approaches and the development of behavioral interventions.

Adult↗

Severe, demyelinating leukoencephalopathy in AIDS patients on antiretroviral therapy.

OBJECTIVES: To describe a severe form of demyelinating HIV-associated leukoencephalopathy in AIDS patients failing highly active antiretroviral therapy (HAART), its relationship to clinical and neuroimaging findings, and suggest hypotheses regarding pathogenesis. DESIGN AND METHODS: AIDS patients who failed HAART and displayed severe leukoencephalopathy were included. All cases had detailed neuromedical, neuropsychological, neuroimaging and postmortem neuropathological examination. Immunocytochemical and PCR analyses were performed to determine brain HIV levels and to exclude other viruses. RESULTS: Seven recent autopsy cases of leukoencephalopathy in antiretroviral-experienced patients with AIDS were identified. Clinically, all were severely immunosuppressed, six (86%) had poorly controlled HIV replication despite combination antiretroviral therapy, and five (71%) had HIV-associated dementia. Neuropathologically, all seven had intense perivascular infiltration by HIV-gp41 immunoreactive monocytes/macrophages and lymphocytes, widespread myelin loss, axonal injury, microgliosis and astrogliosis. The extent of damage exceeds that described prior to the use of HAART. Brain tissue demonstrated high levels of HIV RNA but evidence of other pathogens, such as JC virus, Epstein-Barr virus, cytomegalovirus, human herpes virus type-8, and herpes simplex virus types 1 and 2, was absent. Comparison of the stages of pathology suggests a temporal sequence of events. In this model, white matter damage begins with perivascular infiltration by HIV-infected monocytes, which may occur as a consequence of antiretroviral-associated immune restoration. Intense infiltration by immune cells injures brain endothelial cells and is followed by myelin loss, axonal damage, and finally, astrogliosis. CONCLUSIONS: Taken together, our findings provide evidence for the emergence of a severe form of HIV-associated leukoencephalopathy. This condition warrants further study and increased vigilance among those who provide care for HIV-infected individuals.

AIDS Dementia Complex↗

Progression to neuropsychological impairment in human immunodeficiency virus infection predicted by elevated cerebrospinal fluid levels of human immunodeficiency virus RNA.

BACKGROUND: If cerebrospinal fluid (CSF) human immunodeficiency virus (HIV) RNA levels are elevated before the development of neuropsychological (NP) impairment, such an observation would support prospective monitoring of CSF HIV RNA levels as well as therapeutic interventions designed to lower CSF HIV levels. OBJECTIVE: To determine whether increased CSF HIV RNA levels at an earlier time predict subsequent progression to NP impairment in HIV-infected subjects. METHODS: We examined 139 subjects in a prospective cohort study. Comprehensive NP, neuromedical, and laboratory evaluations were performed at initial and follow-up visits at least 6 months apart. Human immunodeficiency virus RNA levels in plasma and CSF were measured with a commercially available, polymerase chain reaction-based assay. To assess the robustness of our findings, we analyzed changes in NP performance over time in 2 ways. First, we used masked clinical ratings of global NP performance to identify individuals who were initially NP normal, and then determined, in a similarly blinded fashion, which of these subjects subsequently became NP impaired. Second, in a separate analysis, we assessed change in subjects' raw scores on each of a series of NP test measures between baseline and follow-up. RESULTS: Among subjects who were not impaired at the initial visit, higher levels of HIV RNA in CSF significantly predicted progression to global NP impairment at the follow-up evaluation. Cerebrospinal fluid HIV RNA levels outperformed other clinical and laboratory measures in predicting progression to NP impairment. Higher CSF HIV RNA levels were associated with worsening performance on tests of attention, learning, and motor function. CONCLUSION: Because elevated CSF HIV RNA levels (>or=200 copies/mL) predict subsequent progression to NP impairment, monitoring of CSF viral load and therapy to reduce CSF HIV RNA levels may be clinically warranted, even if impairment is not identified at the time of lumbar puncture.

Adult↗

Nonacute (residual) neuropsychological effects of cannabis use: a qualitative analysis and systematic review.

Because there is a possibility that cannabis or cannabis-like molecules might be used as treatments for certain conditions in the future, it becomes important to consider the possible adverse effects of these compounds. In this paper, the authors review the evidence for persisting effects of nonacute cannabis use on the central nervous system, as reflected by alteration in neuropsychological performance. From the 40 articles that met criteria for inclusion in this review, the authors could not detect consistent evidence for persisting neuropsychological deficits in cannabis users; however, 22 of the 40 studies reported at least some subtle impairments. The inability to reach a firm conclusion results largely from methodological limitations inherent in most studies. These are considered in detail to inform future studies on (nonacute) consequences of cannabis consumption on cognitive abilities.

Cognition Disorders↗

Temporal stability of acute stress-induced changes in leukocyte subsets and cellular adhesion molecules in older adults.

This study investigated the temporal stability of enumerative immune and catecholamine responses to acute psychosocial stress in 67 Alzheimer's caregivers ages 56-82 years (45 women and 22 men) who were required to prepare and deliver two 3-min speeches on three occasions at 2-week and 6-week intervals. All leukocyte subsets and adhesion molecules (CD62L and CD11a) changed significantly from rest to postspeak at each of the three testing sessions (p's <.0005). Responses showed moderate to high temporal stability across baseline and absolute task values (r's =.65-.96). Reliability was predictably lower for both forms of change scores (r's = -.16-.64). The level of temporal stability achieved is comparable to that seen previously in younger adults, indicating that acute psychosocial stress produces reliable changes in circulating leukocytes and cell adhesion molecules in older adults.

Aged↗

Motivations associated with methamphetamine use among HIV+ men who have sex with men.

Previous research has documented an association between methamphetamine (meth) use and high-risk sex among HIV- men who have sex with men (MSM); however, little is known about the sexual risk behaviors of HIV+ meth-using MSM. The purpose of this study was to explore personal motivators of meth use among HIV+ MSM, and to elaborate upon the interaction between meth use and risky sex. Thematic analysis of qualitative data from 25 HIV+ MSM revealed meth use was associated with high rates of anal sex, low rates of condom use, multiple sex partners, sexual marathons, and anonymous sex. Personal motivations associated with meth use included: sexual enhancement; and self-medication of negative affect associated with HIV+ serostatus. A variety of treatment approaches are used to describe how client insights into motivations can be used by clinicians to promote change in drug use and sexual risk behavior.

Adult↗

A placebo-controlled randomized clinical trial of nortriptyline for chronic low back pain.

To assess the efficacy of nortriptyline, a tricyclic antidepressant, as an analgesic in chronic back pain without depression, we conducted a randomized, double-blind, placebo-controlled, 8-week trial in 78 men recruited from primary care and general orthopedic settings, who had chronic low back pain (pain at T-6 or below on a daily basis for 6 months or longer). Of these 57 completed the trial; of the 21 who did not complete, four were withdrawn because of adverse effects. The intervention consisted of inert placebo or nortriptyline titrated to within the therapeutic range for treating major depression (50-150 ng/ml). The main outcome endpoints were pain (Descriptor Differential Scale), disability (Sickness Impact Profile), health-related quality of life (Quality of Well-Being Scale), mood (Beck Depression Inventory, Spielberger State Anxiety Inventory, Hamilton Anxiety/Depression Rating Scales), and physician rated outcome (Clinical Global Impression). Reduction in pain intensity scores was significantly greater for participants randomized to nortriptyline (difference in mean change 1.68, 95%-0.001, CI -3.36, P = 0.050), with a reduction of pain by 22% compared to 9% on placebo. Reduction in disability marginally favored nortriptyline (P = 0.055), but health-related quality of life, mood, and physician ratings of overall outcome did not differ significantly between treatments. Subgroup analyses of study completers supported the intent-to-treat analysis. Also, completers with radicular pain on nortriptyline (n = 5) had significantly (P < 0.05) better analgesia and overall outcome than did those on placebo (n = 6). The results suggest noradrenergic mechanisms are relevant to analgesia in back pain. This modest reduction in pain intensity suggests that physicians should carefully weigh the risks and benefits of nortriptyline in chronic back pain without depression.

Adult↗

One-year follow-up of first onset low back pain.

Efforts to examine the process and risk of developing chronic back pain have relied generally upon retrospective study of individuals with already established pain. In an alternative approach to understanding the clinical course and evolution of low back disorders, a cohort of 76 men experiencing their first episode of back pain was assessed prospectively at 2, 6 and 12 months following pain onset. Standard measures of pain (Descriptor Differential Scale: DDS), disability (Sickness Impact Profile: SIP), and distress (Beck Depression Inventory: BDI) were employed to classify the sample into five groups: Resolved, Pain Only, Disability/Distress Only, Pain and Mild Disability/Distress, and Clinical Range. At both 6 and 12 months post pain onset, most (78%, 72% respectively) of the sample continued to experience pain. Many also experienced marked disability at 6 months (26%) and 12 months (14%). At 12 months, no participants had worsened relative to the 2-month baseline. Doubly multivariate analyses of variance (MANOVAs) were employed to compare baseline groups (Pain Only, Pain and Mild Disability/Distress, Clinical Range) on the DDS, SIP, and BDI across time. The group by time interaction from 2 through 12 months was reliable, with greatest change occurring in the Clinical Range group in disability and distress; interestingly, the decrease in pain was comparable among all groups. Follow-up tests across measures demonstrated greater change in the early (2-6-month) interval and relative stability in the later (6-12-month) interval. Comparison of those classified as 'improvers' with those who did not improve from 2 to 12 months showed similar findings. The clinical course of first onset back pain may be prolonged for many patients, and involves a continuum of related disability and distress. Individuals at risk for marked symptoms 1 year after an initial episode of back pain can be identified early, and prompt treatment might reduce the risk of pain chronicity.

Adolescent↗

Psychosocial factors discriminate multidimensional clinical groups of chronic low back pain patients.

Previous studies have empirically defined clinical subgroups of chronic low back pain (CLBP) patients, based on differing patterns of pain, disability and emotional distress. Because these identified groups generally are comparable in terms of physical and demographic variables, variation in functional status cannot be adequately explained by medical or social factors. In the present study we evaluated whether other psychosocial factors (stress, coping attempts, and satisfaction with social supports) might differentiate the observed groups. A discriminate function analysis indicated that ratings of life adversity, coping, and social support statistically differentiate clinical groups of CLBP patients. Patients categorized as chronic pain syndrome (i.e., high levels of pain, disability and depression) reported greater life adversity, more reliance on passive/avoidant coping strategies, and less satisfaction with social support networks. Patients categorized as having good pain control (i.e., low levels of pain, disability and depression) reported less life adversity, less reliance on passive/avoidant coping strategies, and more satisfaction with social support networks. Finally, a mixed picture of less life adversity, but more reliance on passive/avoidant coping strategies and more satisfactory social support networks was reported by patients categorized in the positive adaptation to pain group (i.e., high levels of pain, but relatively low levels of disability and depression). These findings suggest that psychosocial factors may be important and complex correlates of multidimensional clinical presentations of CLBP. Psychosocial factors may also offer an avenue for intervention across 3 key dimensions of CLBP.

Adaptation, Psychological↗

Coping activities in chronic low back pain: relationship with depression.

To help clarify the nature of coping activities in chronic pain, this study compared how depressed (n = 37) and non-depressed (n = 40) chronic low back pain (CLBP) patients attempted to cope with pain-specific and general non-pain life stressors, relative to matched healthy control subjects (n = 40). We hypothesized that depressed mood, rather than pain alone, would account for differences in coping activities between groups. Specifically, we expected that depressed CLBP patients would report a greater proportion of passive and avoidant coping responses and less active problem solving coping attempts than non-depressed patients and controls. Results indicated that depressed CLBP patients reported more passive-avoidant coping activities than did non-depressed CLBP patients and controls, whereas coping responses were similar for non-depressed CLBP patients and controls. Additionally, subjects across groups tended to report more passive-avoidant coping in response to the specific back pain stressor (i.e., exacerbation of back pain during activity) than to other life stressors. Finally, the magnitude of reported differences in coping attempts across groups varied as a function of the type of stressor (i.e., specific back pain stressor vs. general stressful life events), particularly with regard to a disinclination to seek social support in response to the back pain exacerbation. We conclude that: (1) chronic back pain patients may employ different coping activities when attempting to manage pain exacerbations than when confronting more general life stressors, and (2) an increased rate of passive-avoidant coping responses (relative to matched health controls) is associated with the combination of CLBP and concurrent depressed mood, rather than with CLBP alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Psychological↗

Prevalence, onset, and risk of psychiatric disorders in men with chronic low back pain: a controlled study.

This study used structured diagnostic interviews and DSM-III criteria to assess lifetime prevalence and pre-morbid risk of psychiatric disorder in a sample of men with long-standing chronic back pain (CLPB) attending a primary care clinic. A control group of age and demographically matched men without history of back pain was also studied. Compared to controls, men with CLBP had significantly higher lifetime rates of major depression (32% vs. 16%), alcohol use disorder (64.9% vs. 38.8%), and a major anxiety disorder (30.9% vs. 14.3%). Almost all CLBP men ever experiencing a mood disorder reported recurrent, not single, episodes. The 6 month point prevalence of major depression, but not other disorders, was also significantly elevated for men with CLBP. In CLBP, the first episode of major depression generally (58.1%) followed pain onset. While the initial major depressive episode usually commenced within the first 2 years of established pain, late onset mood disorder was also common. By comparison in most cases (81%) onset of alcohol use disorders considerably preceded pain. When an age-matching procedure was used to gauge relative vulnerability to psychiatric illness in patients and controls, CLBP patients had significantly higher pre-pain rates of alcohol use disorder but not depression. After age of pain onset, CLBP subjects had over 9 times the risk of developing major depression, but had similar rates of developing alcoholism. We conclude that (1) alcohol use disorders rather than depression may increase risk of developing CLBP, and (2) risk of new onset and recurrent major depression remains high for men throughout their pain career. This suggests that psychological adaptation to long-standing pain may be less successful than previously thought, especially with regard to recurrent mood disorder.

Adult↗

Depressed mood in chronic low back pain: relationship with stressful life events.

This study investigated the relationship between stressful life events and depressed mood in chronic low back pain (CLBP), using both self-report and observer-rated assessments of life happenings and depression. We hypothesized that CLBP patients with depressed mood (N = 15) would report significantly more untoward life events and ongoing life difficulties compared to CLBP patients without depressed mood (N = 17) and controls (N = 19). This prediction was confirmed. Subjects also were rated as being either in a high stress or low stress condition. Patients with depressed mood were more likely to be in the high stress condition than were either non-depressed patients or volunteers. Furthermore, the increased stress reported by the distressed group appeared to be a direct consequence of back pain-related life events, rather than from other life problems. We conclude that previously reported associations between life events and CLBP are a function of the relationship between stressful life events and depressive symptoms, which are prevalent in CLBP.

Adult↗

Utilization of drug treatment programs by methamphetamine users: the role of social stigma.

We examined the link between drug use stigma and use of drug treatment services in a sample of 292 heterosexually identified, methamphetamine (meth) users. Participants who had ever been in treatment for their meth use (N = 82) were compared with those who had never been in treatment (N = 210). Three dimensions of stigma proposed by Link et al.(1) were examined. In univariate analyses, participants who had never been in treatment for meth use reported significantly more expectations of rejection and endorsed more stigma coping strategies as compared to those who had ever been in treatment. Regression analysis revealed that all three dimensions of stigma distinguished between participants who did and did not receive treatment for their meth use. Stigma is discussed as a potential barrier to drug use treatment.

Adaptation, Psychological↗

Health consequences of Alzheimer's caregiving transitions: effects of placement and bereavement.

OBJECTIVE: To determine the extent to which the chronic stress of Alzheimer's disease caregiving may be alleviated by placement or death of the Alzheimer's disease patient, we prospectively compared groups of caregivers (CG) who continued to care for their Alzheimer's disease spouse at home, CG who placed their spouses, and CG whose spouses died with similarly aged noncaregiving comparison subjects (control subjects). METHODS: A sample of 119 CG who had been studied for at least 18 months at 6-month intervals was included in the present analyses (ie, had at least three assessments). Data were gathered on CG mood, blood pressure, and medical symptoms among 38 CG whose spouses were at home at all three visits (home-home-home [HHH]); 28 CG who placed their spouse at follow-up (home-placed-placed [HPP]); 27 CG whose spouses were placed and subsequently died at follow-up (home-placed-deceased [HPD]); and 26 CG whose spouses died at home (home-deceased-deceased [HDD]). Data were compared with 48 noncaregiving control subjects (NC group). RESULTS: CG in the HPP, HPD, and HDD groups showed improvement in depressive and physical symptoms compared with HHH and NCs. CG had significantly higher systolic blood pressure at rest than did NCs. Both placement and death of the Alzheimer's disease spouse were associated with higher systolic blood pressure in response to postural challenge in CG experiencing these transitions. CONCLUSIONS: Despite improvement seen in mood and medical symptoms among CG who place their spouses or experience the spouse's death, there may be longer term physiological alterations, possibly in sympathoadrenalmedullary arousal, that cause the cardiovascular system to continue to respond to acute stressors such as postural challenge more actively for a period of 6 to 12 months after such transitions.

Affect↗

Association of negative life event stress with coagulation activity in elderly Alzheimer caregivers.

OBJECTIVE: Part of the excess coronary disease rate and overall mortality reported with caregiving stress could relate to a hypercoagulable state. Physiological responses to the chronic distress of caregiving may involve hyperactive sympathetic nervous system responses to superimposed stressors. We wondered whether negative life stress might affect hemostatic function in caregivers. METHODS: The three procoagulant measures thrombin-antithrombin III complex (TAT), fibrin D-dimer (DD), and von Willebrand factor (vWF) antigen were assessed in 54 spousal Alzheimer caregivers (mean age, 73 +/- 6 years). Subjects completed a semistructured interview (Psychiatric Epidemiologic Research Interview, PERI) that assessed for non-caregiving-related life stress (ie, number of negative life events) over the 4-week period before blood sampling. RESULTS: Caregivers reported an average of 2.6 negative life events (range, 0-6). The number of negative life events showed a direct association with plasma DD levels (p =.010). In multiple regression analyses, body mass index (BMI) and life stress were the only significant predictors of DD. Together, BMI, hypertension status, gender, and depression accounted for 23% of the variance in DD (p =.022). After these variables had been controlled for, life stress explained an additional 9% (p =.021) of the variance in DD. On the other hand, the number of life-events did not significantly predict TAT or vWF. CONCLUSIONS: The findings suggest that superimposed life stress on top of the chronic stress of Alzheimer caregiving may elicit a hypercoagulable state that could contribute to coronary disease and to increased overall mortality in this population.

Aged↗