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Biomedical subjects

I Grant

Publications and source records attributed to I Grant.

At least 19 recordsLinked to original sources
PubMed1992

Reduced mortality risk in alcoholics who achieve long-term abstinence.

OBJECTIVES: To determine if alcoholic men who achieved stable abstinence experienced fewer deaths than those who relapsed and to develop a model predictive of premature mortality. DESIGN: A cohort of alcoholic men recruited into a prospective study of neurocognitive effects of alcoholism was followed up from 1 through 11 years. A demographically equated group of nonalcoholic men was also followed up. Alcoholics were classified as stable abstainers or relapsers. SETTING: Alcoholics were patients or ex-patients from a Department of Veterans Affairs Alcoholism Treatment Program and/or members of local chapters of Alcoholics Anonymous. PARTICIPANTS: There were 234 alcoholic men who met the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, criteria for alcohol dependence. Follow-up status regarding relapse and mortality was obtained for 199 alcoholic subjects (85%). Of these, 101 had relapsed and 98 had abstained. Ninety-eight nonalcoholic controls equated for age, education, and sex also participated. Mortality status was obtained for 92 subjects in this group (94%). EXCLUSIONS: Major medical and psychiatric illness and history of nonalcoholic drug abuse. MAIN OUTCOME MEASURE: Death during a follow-up period of 1 through 11 years. Death was ascertained through the National Death Index, the California State Department of Health and Vital Statistics, the State Department of Motor Vehicles, and through personal contact with informants, relatives, and significant others of the subjects. RESULTS: There were 19 deaths among relapsed alcoholics compared with the expected number of 3.83 (99% confidence interval (CI), 9.64 to 33.38). Among abstinent alcoholics there were four deaths (expected = 3.21; 99% CI, 0.67 to 12.59). The standardized mortality ratio for relapsed alcoholics was 4.96, which significantly exceeded the expected ratio (P less than .001), whereas the standardized mortality ratio for abstinent alcoholics (1.25) was indistinguishable from the expected. Cox proportional hazards analysis was used to determine if any of several demographic, medical, cognitive, or drinking history variables (in addition to relapse) helped predict mortality among alcoholics. Only relapse was significantly related to increased mortality (chi 2 = 9.15, P = .003). CONCLUSIONS: Alcoholic men who achieve stable abstinence do not differ from nonalcoholic men in mortality experience; however, alcoholics who relapse die at a rate 4.96 times that of an age-, sex-, and race-matched representative sample from the US Bureau of the Census.

Alcoholism↗
PubMed1992

Visual dysfunction without retinitis in patients with acquired immunodeficiency syndrome.

Patients with human immunodeficiency virus infection may have noninfectious and infectious retinopathies, as well as clinical symptoms consistent with optic nerve dysfunction. Noninfectious acquired immunodeficiency syndrome-related retinopathy is seen in most patients with AIDS. Morphologic studies have shown that the number of retrobulbar optic nerve fibers in patients with AIDS is decreased compared to the number of optic nerve fibers in normal control eyes. To determine whether these patients had a visual dysfunction consistent with damage to the macula and optic nerve, 78 subjects (156 eyes) were studied using color-vision and contrast-sensitivity testing. The Farnsworth-Munsell 100-Hue color-vision test was performed on all subjects and age-corrected color-vision scores for all groups were compared. A significant decrease in color discrimination was found in the patients with AIDS (P less than .001). Contrast-sensitivity testing disclosed a deficit of contrast threshold in patients with AIDS at four of five spatial frequencies and in patients with AIDS-related complex at three of the five spatial frequencies examined. This study demonstrated a functional visual deficit in eyes without retinitis consistent with dysfunction of the macula or optic nerve in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Sensory testing in human immunodeficiency virus type 1-infected men. HIV Neurobehavioral Research Center Group.

Patients with acquired immunodeficiency syndrome frequently suffer peripheral neuropathy. We investigated its prevalence and relationship to clinical stage of human immunodeficiency virus (HIV) infection using quantitative sensory testing and nerve conduction testing. Vibratory threshold was determined in the right great toe and index finger of 179 men seropositive for HIV (28 with acquired immunodeficiency syndrome [AIDS] or AIDS-related complex [ARC], 151 asymptomatic) and 32 HIV-seronegative controls. None had clinical peripheral neuropathy. Abnormal threshold was control mean plus 2.5 SDs. In the toe, 10 (36%) of 28 subjects with AIDS or ARC had abnormal vibratory thresholds, compared with seven (5%) of 151 asymptomatic seropositive subjects and none of 32 controls. A subgroup of 168 seropositive subjects underwent nerve conduction testing. Abnormality rates were similar, but abnormalities of nerve conduction coincided with quantitative sensory testing abnormalities in only half the cases. Mean (+/-SD) vibratory threshold was significantly greater in subjects with AIDS or ARC (3.00 +/- 0.51 vibratory units) than in asymptomatic subjects (1.56 +/- 0.27 vibratory units) and controls (1.63 +/- 0.54 vibratory units). Finger abnormality rates did not differ, although subjects with AIDS or ARC had greater mean vibratory threshold. Subclinical peripheral neuropathy is thus related to stage of HIV infection and is present by quantitative sensory testing in 36% of patients with AIDS or ARC.

AIDS-Related Complex↗
PubMed1992

The determination of low d5-phenylalanine enrichment (0.002-0.09 atom percent excess), after conversion to phenylethylamine, in relation to protein turnover studies by gas chromatography/electron ionization mass spectrometry.

A gas chromatography/mass spectrometry (GC/MS) method for measuring very low levels of enrichment of d5-phenylalanine (0.002-0.09 atom percent excess) is described. This method makes it possible to determine the enrichment of amino acid incorporated into tissue protein during studies of protein synthesis in man. Phenylalanine is enzymatically converted to phenylethylamine and the d5-enrichment is measured in the heptafluorobutyryl derivative by selective-ion recording under electron ionization conditions. The coefficients of variation for muscle-protein hydrolysate samples enriched with d5-phenylalanine at the 0.005 and 0.05 atom percent excess levels were 6.0 and 1.2%, respectively. This precision at low enrichment and the small amount of protein needed (about 1 mg) provide real advantages for clinical studies of tissue protein synthesis. Moreover, in contrast to the conventional approach which uses GC/MS for plasma amino acids (typically 2-20 atom percent excess) but gas isotope-ratio mass spectrometry for protein-bound amino acids, the enrichment of both plasma-free and protein-bound d5-phenylalanine can be measured with a single instrument.

Gas Chromatography-Mass Spectrometry↗
PubMed1992

Symptoms of illness in late adulthood are related to childhood social deprivation and misfortune in men but not in women.

Experiencing adverse life events during childhood may increase vulnerability to physical illnesses and psychological disorders during adulthood. We developed an Early Life Events Questionnaire (ELEQ) with 12 scales and administered it to 92 relatively healthy elderly individuals (29 men and 63 women). A canonical-correlation analysis of the 12 ELEQ scales and physical and psychological symptoms revealed a significant canonical correlation. The results indicate that those who grew up in a family with a harsh climate and whose affiliation needs were not met tended to have more psychological and physical symptoms in old age. Regression analysis revealed that, in men, early life events accounted for 42% of the variance in physical symptoms and 39% in psychological symptoms. No significant relationship, however, was found between ELEQ scales and health outcomes in women. These results suggest that women may be less vulnerable than men to the adverse health consequences of childhood deprivation and other misfortunes.

Age Factors↗
PubMed1992

Effects of recalled childhood gender nonconformity on adult genitoerotic role and AIDS exposure. HNRC Group.

The connections between childhood gender nonconformity (assessed by the Freund Feminine Gender Identity Scale, or FGI) and adult genitoerotic role (assessed by a sex history) were examined. The core sample was a group of 106 men who had sex with other men before 1980 and who are currently enrolled in two longitudinal studies of AIDS. Although other workers have cautioned against assuming a priori that childhood gender role is inherently related to adult preferences for particular sexual acts, our data suggest that there is at least a statistical association between these two concepts. In particular, the FGI (and many of its factors and items) are significantly associated with preferences for receptive anal intercourse and, less clearly, with oral-anal contact--but not with oral-genital intercourse or insertive and intercourse. Suggestions for AIDS prevention and safe-sex awareness are made on the basis of these findings. The data also suggest that in sex research involving homosexual men, the correct genitoerotic role distinction is not insertive vs. receptive behaviors, or even insertive vs. receptive and intercourse, but receptive anal intercourse vs. all other behaviors.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Epidural blood patch in the HIV-positive patient. Review of clinical experience. San Diego HIV Neurobehavioral Research Center.

To characterize the natural history of autologous epidural blood patch (EBP) in human immunodeficiency virus (HIV)-seropositive patients, records from an ongoing longitudinal study of the neuropsychological manifestations of HIV infection were retrospectively reviewed. Of 252 participants (218 HIV-seropositive, 34 HIV-seronegative) who underwent at least one diagnostic lumbar puncture, 9 (7 seropositive, 2 seronegative) required EBP for post-dural puncture headache. After EBP, 6 of the seropositive subjects underwent serial neuropsychological evaluations over periods ranging from 6 to 24 months; none of these six subjects had a decline in neurocognitive performance or other adverse neurologic or infectious sequelae. We were unable to identify morbidity attributable to EBP in the HIV-seropositive patient followed for as long as 2 yr.

Adult↗
PubMed1992

Relationship of cerebrospinal fluid immune activation associated factors to HIV encephalitis.

OBJECTIVES AND DESIGN: Because macrophages are the predominant immune cell and the predominant infected cell in the brains of patients with HIV encephalitis, we studied macrophage and immune activation-associated factors in the cerebrospinal fluid (CSF) from 39 autopsied AIDS cases for whom complete neuropathologic evaluation of the brain was available. RESULTS: CSF HIV p24 antigen was present in less than one-third of cases (11 out of 39). Less than half of the autopsies with moderate to severe parenchymal infection by HIV had high levels of CSF p24, although all autopsies with elevated levels of HIV p24 had moderate to severe HIV encephalitis. Elevated levels of cytokines, beta 2-microglobulin, neopterin, and quinolinic acid were observed. CONCLUSIONS: Although many of the CSF findings showed a strong correlation with each other, none showed a strong correlation with the severity of HIV infection of the brain itself. The absence of a close association between CSF abnormalities and HIV encephalitis could reflect the abundance of complicating opportunistic infections in these terminally ill patients or the inadequacy of CSF as a marker of basal ganglia involvement in HIV encephalitis. These findings complicate interpretation of clinical studies of CSF in patients with AIDS where neuropathologic evaluation is unavailable.

AIDS Dementia Complex↗
PubMed1992

The relationship of life adversity, social support, and coping to hospitalization with major depression.

We evaluated the relationship between life events, social support, coping, and depression in 27 male inpatients meeting the requirements for Research Diagnostic Criteria major depressive disorder and in 35 age- and sex-matched nonpatients. Overall, the hospitalized depressed patients reported significantly more events and difficulties than did the controls, but this difference in statistical significance disappeared after excluding from analysis "non-independent" happenings which could have been brought on by depression. More hospitalized depressed patients (23 of 27, or 85%) than controls (8 of 35, or 22.9%) experienced markedly threatening events and difficulties ("marked adversities") in the 6 months before their interview. The depressed group also reported having significantly fewer social supports, being less satisfied with the emotional component of this support, and using more emotion-focused coping than the controls. A discriminant analysis predicted depressive status from a combination of marked adversities, reduced number of social supports, and greater use of emotion-focused coping. The results indicate that the relationship of life events to depression is complex. The excess number of events might be partly a product of dysfunctional behavior that "produces" depression-related events which might, in turn, exacerbate depression; simultaneously, patients are more likely to experience highly adverse events which might precipitate the depression in the first place. Reduced social supports and the use of emotion-focused coping appear to also be associated with hospitalization for major depression.

Adaptation, Psychological↗
PubMed1992

Long-term abstinent alcoholics have normal memory.

It is generally believed that many non-Korsakoff alcoholics have subtle defects in memory. To determine whether such defects vary as a function of length of abstinence (LOA), we performed extensive memory testing with: (1) recently detoxified (n = 31; LOA-29 days); (2) intermediate-term abstinent (n = 28; LOA = 1.9 years); (3) long-term abstinent (n = 32; LOA-7.0 years) alcoholics; and (4) nonalcoholic controls (n = 37). All subjects were matched on age and education. Alcoholics were matched on years of alcoholic drinking. Memory measures were divided into the following domains: verbal learning, verbal recall, visual learning, visual recall, and paired associate learning. A series of MANOVAs were conducted that revealed a significant relationship between visual learning and length of abstinence, and a significant interaction between age and length of abstinence on visual recall. Long-term abstinent subjects were not significantly different from controls on any test. We conclude that memory disturbance demonstrable among recently detoxified alcoholics in the early weeks of their abstinence is not evident in demographically matched long-term abstinent alcoholics with similar drinking histories.

Adult↗
PubMed1992

Incidence of AIDS dementia in a two-year follow-up of AIDS and ARC patients on an initial phase II AZT placebo-controlled study: San Diego cohort.

In a prospective study to determine the incidence of clinical dementia in patients with AIDS and ARC, 29 men and 3 women, 19 with ARC and 13 with AIDS, were examined neurologically and neuropsychologically every 6 months for 2 years during a placebo-controlled zidovudine (AZT) licensing trial. Most received two MRI brain scans. Although no patient was clinically demented at baseline, 9 (28%) developed dementia during the 2 years. Progression to dementia was associated with neuropsychological deterioration and with worsening on MRI during a preceding 6-month period, but not with baseline treatment group assignment. The results suggest that patients at CDC Stage IV who do not receive antiretroviral treatment earlier in their illness may develop clinical dementia at an annual rate of about 14%.

AIDS Dementia Complex↗
PubMed1991

Effects of human recombinant interleukin-1 beta on protein synthesis in rat tissues compared with a classical acute-phase reaction induced by turpentine. Rapid response of muscle to interleukin-1 beta.

The early time course (1, 3, 9, 24 h) of changes in rates of protein synthesis (ks) in liver and three different muscles (gastrocnemius, soleus and heart) was investigated after injection of saline, interleukin-1 beta (IL-1) or turpentine in rats. IL-1 injection induced a consistent increase in body temperature of about 3 degrees C between 3 and 5 h, but thereafter a hypothermic response occurred. With turpentine, a delayed fever response with a peak value by 9 h was observed. Both IL-1 and turpentine had no effect on protein synthesis in the small intestine, but produced a significant increase in ks in the liver at 9 h. By 24 h in IL-1-treated animals, liver ks had returned back to control values, whereas the turpentine-treated group showed a progressive rise in ks. Gastrocnemius and soleus muscles exhibited a significant fall in ks at 9 h after IL-1 and turpentine injection compared with the control. In contrast, the ks of heart muscle increased at 3-9 h after IL-1 injection, but there was no effect of turpentine. Thus for the first time a marked decrease of protein synthesis in skeletal muscle in response to IL-1 could be demonstrated.

Acute-Phase Proteins↗
PubMed1991

The generalized pattern of neuropsychological deficits in outpatients with chronic schizophrenia with heterogeneous Wisconsin Card Sorting Test results.

Forty schizophrenic outpatients and 40 normal subjects were assessed using extensive clinical (eg, Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms and Scale for the Assessment of Positive Symptoms) and neuropsychological (extended Halstead-Reitan Battery) measures. The schizophrenic patients had multiple neuropsychological deficits on tests of complex conceptual reasoning, psychomotor speed, new learning and incidental memory, and both motor and sensory-perceptual abilities. Neuropsychological impairment correlated more strongly with negative than positive symptoms. Overall, the schizophrenic outpatients showed relatively modest increases in the number of perseverative responses on the Wisconsin Card Sorting Test of abstraction flexibility. A subgroup of these schizophrenic patients seemed to be particularly impaired on the Wisconsin Card Sorting Test. This pattern of results, in conjunction with previous studies, supports the idea that, while some schizophrenic patients may have fixed, frontally based dysfunctions, these dysfunctions may be most prominent, and even fixed, in deteriorated, kraepelinian patients. These data provide evidence for diffuse and far-reaching deficits in a majority of outpatients with chronic schizophrenia.

Adult↗
PubMed1991

Neuropeptide Y and natural killer cell activity: findings in depression and Alzheimer caregiver stress.

A reduction in immune function has been found in patients with a major depressive disorder and in persons undergoing severe life stress. This study investigated the association between increased sympathetic nervous system activity and reduced natural killer (NK) cytotoxicity in depression and Alzheimer caregiver stress. NK activity and plasma concentrations of epinephrine, norepinephrine, and neuropeptide Y were measured in depressed patients (n = 19) and age- and gender-matched controls (n = 19), and in Alzheimer spousal caregivers (n = 48) and matched noncaregiver controls (n = 17). Plasma levels of neuropeptide Y, but not circulating basal levels of catecholamines, were significantly (P less than 0.01) elevated in the depressed patients and in the caregivers compared with respective controls. NK activity was significantly (P less than 0.001) lower in the depressed patients than in their controls, but not different between the caregivers and the noncaregiver controls. Circulating concentrations of neuropeptide Y, but not catecholamines, were inversely correlated (r = -0.31, P less than 0.001) with NK activity. In addition, multiple regression analyses demonstrated that the significant (P less than 0.01) association between neuropeptide Y and natural cytotoxicity was independent of the relative contribution of age and basal and dynamic levels of epinephrine and norepinephrine. These findings suggest that increased sympathetic nervous system activity and the release of neuropeptide Y may be associated with the modulation of NK cytotoxicity.

Alzheimer Disease↗
PubMed1991

Reduced cerebral grey matter observed in alcoholics using magnetic resonance imaging.

Twenty-eight chronic alcoholics and 36 age- and sex-matched non-alcoholic controls were examined with magnetic resonance imaging and brain morphometric analyses. Results confirmed large increases in subarachnoid cerebrospinal fluid (CSF) volume and mild ventricular enlargement in the alcoholics and revealed associated volume reductions of localized cortical and subcortical cerebral structures. Volume losses in the diencephalon, the caudate nucleus, dorsolateral frontal and parietal cortex, and mesial temporal lobe structures were the most prominent. Significant correlations between increments in cortical and ventricular CSF and decrements in the volume of cortical and subcortical grey matter were noted. Although there was little evidence for relationships between performance on neuropsychological tests and volume of grey matter structures, significant correlations between some cognitive measures and subcortical and cortical fluid volumes were found. The parallels between this pattern of affected structures and recent neuropathological findings are discussed.

Adult↗