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Biomedical subjects

I Grant

Publications and source records attributed to I Grant.

At least 145 records · Page 8Linked to original sources
PubMed1994

Response of protein synthesis in human skeletal muscle to insulin: an investigation with L-[2H5]phenylalanine.

The role of insulin in the regulation of muscle protein synthesis in adult humans has been investigated with intravenous infusion of insulin at levels comparable with those observed after normal feeding. Glucose was also infused to maintain euglycemia. Muscle protein synthesis was measured in six healthy subjects before and during insulin and glucose infusion from the incorporation of L-[2H5]phenylalanine into the protein of vastus lateralis sampled by percutaneous biopsy. L-[2H5]phenylalanine was given as a single injection of a flooding amount (45 mg/kg). The relatively low levels of enrichment of phenylalanine in protein (0.005 atom%) were measured by modified gas chromatography-mass spectrometry and verified by comparison with incorporation of L-[2,6-3H]phenylalanine. Similarity of enrichment in tissue-free and plasma pools (flooding) and linear incorporation over the period of measurement were also verified. The fractional rate of muscle protein synthesis in the group of postabsorptive subjects was 1.65 +/- 0.11% (SE)/day. The rate was unaltered by insulin and glucose infusion, 1.66 +/- 0.16%/day.

Adult↗
PubMed1994

Changes in regional protein synthesis in rat brain and pituitary after systemic interleukin-1 beta administration.

A convenient and sensitive method has been developed for measuring changes in protein synthesis in discrete areas of the brain and pituitary of conscious freely moving rats. A single injection of high-concentration low-specific activity L-[35S]methionine is given to flood amino acid precursor pools, thereby equalizing the specific activity of the L-[35S]methionine throughout the tissue. Unincorporated L-[35S]methionine is removed from cryostat sections by treatment with perchloric acid (2%) before quantitative autoradiography. The sensitivity of this technique is demonstrated by the detection of changes in protein synthesis in regions of the brain and pituitary after systemic administration of interleukin-1 beta, a cytokine that has centrally mediated effects but which is not thought to cross the blood-brain barrier. Areas of the brain found to exhibit significant increases in protein synthesis were the subfornical organ, the choroid plexus, the medial habenular, the dentate gyrus, and the anterior and posterior lobes of the pituitary. In the brain, the cingulate cortex and the pineal gland showed significant decreases in the rate of protein synthesis.

Animals↗
PubMed1994

HIV-associated psychosis: a study of 20 cases. San Diego HIV Neurobehavioral Research Center Group.

OBJECTIVE: Psychosis is an uncommon but serious complication of infection with HIV. This article presents the results of a study of HIV-infected individuals with psychosis. METHOD: The authors evaluated 20 HIV-infected men who had noniatrogenic new-onset psychosis without delirium, current substance abuse, or previous psychotic episodes. Clinical, neuropsychological, CSF, magnetic resonance imaging, and neuropathologic assessments were made. A comparison group consisting of 20 nonpsychotic HIV-infected men matched to the psychotic subjects with respect to age, race, years of education, and Centers for Disease Control HIV stage was also evaluated. RESULTS: The psychotic patients differed from the nonpsychotic comparison subjects in having significantly higher rates of past stimulant and sedative/hypnotic abuse or dependence and, at follow-up, a significantly higher rate of mortality. They also showed a trend toward greater global neuropsychological impairment. CONCLUSIONS: New-onset psychosis may be, at least in part, a manifestation of an HIV-associated encephalopathy.

AIDS Dementia Complex↗
PubMed1994

Postconcussional disorder: time to acknowledge a common source of neurobehavioral morbidity.

Closed head injuries are common, affecting approximately 2 million people annually in the United States. The majority of these are "mild" in the sense of not being associated with prolonged unconsciousness, intracranial bleeding, skull fracture, or protracted periods of confusion. Yet a proportion of such "mild" injuries are accompanied by persisting cognitive, vegetative, and affective-behavioral sequelae, some of which affect day-to-day life. We argue that there is sufficient research to indicate that postconcussional symptoms occur and that they tend to have a predictable configuration. It is necessary to recognize the existence of "Postconcussional Disorder" in our nosology in order to provide more prompt diagnosis and management and to facilitate scholarly communication and research regarding this important neurobehavioral disorder.

Cognition Disorders↗
PubMed1994

Natural history of neuropsychiatric manifestations of HIV disease.

The neuropsychiatric manifestations of HIV disease include neurobiologic and psychobiologic phenomena. The former consist of primary CNS complications caused directly by HIV, and include cognitive disorders (mild neurocognitive disorder and HIV-associated dementia) and other CNS diseases such as myelopathy and the demyelinating neuropathies; and secondary disorders (principally deliria) occasioned by opportunistic infections, neoplasms, cerebrovascular events, and the effects of metabolic derangements and medications. The latter (psychobiologic) phenomena reflect efforts to cope with various nodal, or transition points, in HIV disease; such points of transition include time of serostatus determination, adaptation to asymptomatic seropositivity, response to early medical symptomatology, and later transition to frank AIDS. Anxiety symptoms and various efforts to cope with anxiety (e.g., denial, anger, withdrawal, hypochondriacal preoccupation) all can punctuate these transition points. Additionally, there may be reactivation of long-standing psychopathology (e.g., depression) in seropositive individuals who tend to belong to a group that has an elevated prevalence of pre-infection psychiatric disorder. These interacting neurobiologic and psychobiologic phenomena pose challenges to the psychiatrist who must develop a good understanding of the medical aspects of HIV infection, as well as the neuropsychiatry of AIDS. In this way psychiatric physicians can play an important role in early identification of neuropsychiatric complications, assist the medical team to anticipate emotional and behavioral disturbances, and develop treatment plans that maximize our ability to help those with HIV infection achieve the best possible quality of life.

AIDS Dementia Complex↗
PubMed1993

Magnetic resonance imaging morphometric analysis of cerebral volume loss in human immunodeficiency virus infection. The HNRC Group.

Magnetic resonance imaging was used to compare male subjects seropositive for antibody to human immunodeficiency virus type 1 (HIV positive), with and without medical symptoms, with two groups of men who were seronegative (HIV negative). The control subjects included men at high risk for exposure to HIV-1 and those at low risk. None of the HIV-positive subjects met criteria for HIV-associated dementia or had detectable opportunistic brain disease. Quantitative image-analytic techniques were used to estimate volumes of ventricular and cortical cerebrospinal fluid, cerebral white matter, and cortical and subcortical gray matter structures. Relative to low-risk group control subjects and asymptomatic HIV-positive subjects, nondemented but medically symptomatic HIV-positive subjects showed significant increases in cerebrospinal fluid, reduced volume of cerebral white matter, and reduced cerebral gray matter volumes. Unexpectedly, however, some cerebrospinal fluid increases and gray matter volume decreases were present in the seronegative high-risk control subjects as well.

Adult↗
PubMed1993

A factor analysis of the Klein sexual orientation grid in two disparate samples.

Many researchers interested in sexual orientation can be separated into two camps: The "lumpers," who try to reduce sexual classifications to as small a number of categories as possible, and the "splitters," who try to show differences among groups and individuals that make classification schemes increasingly difficult and/or intricate. We report factor analyses of the Klein Grid (a questionnaire with 21 sexual orientation items) to see how many factors emerge in two samples of strikingly different origins. In both samples, the first factor to emerge loaded substantially on all of the Klein Grid's 21 items. This factor accounted for a majority of the variance. In both samples, a second, correlated factor emerged which indexed a separation between most of the items and those having to do with social and/or emotional preferences. In both samples, a third correlated factor also emerged, but this factor differed between the two populations: one refined the social/emotional distinction and the other distinguished ideal behavior from past and current behavior. We conclude on the basis of our analysis that both the lumpers and the splitters are correct.

Bisexuality↗
PubMed1993

Cerebral vein thrombosis due to hereditary antithrombin III deficiency.

Cerebral vein thrombosis, also called superior sagittal sinus thrombosis, is a well recognized clinical and radiologic entity associated with a variety of medical disorders. We report a patient with fatal cerebral vein thrombosis following myelography, in whom the cause was familial antithrombin III (AT3) deficiency. Unsuspected AT3 deficiency should be considered in cases of unexplained cerebral venous thromboses.

Adult↗
PubMed1993

Responses of tissue protein synthesis to nutrient intake in rats exposed to interleukin-1 beta or turpentine.

1. The influence of an acute-phase reaction on the ability of protein synthesis rates in liver and three different muscles (gastrocnemius, soleus and heart) to respond to a short intravenous infusion of nutrients (glucose plus amino acids) was investigated during experimental inflammation induced by injection of human recombinant interleukin-1 beta or turpentine in young male rats. 2. Interleukin-1 beta induced a consistent increase of 3 degrees C in body temperature between 3 and 5 h after injection, whereas turpentine induced a delayed fever, peaking by 13 h. 3. Interleukin-1 beta and turpentine stimulated fractional rates of protein synthesis in liver. The synthesis rate was inhibited by interleukin-1 beta in gastrocnemius and soleus muscle, but an elevation was seen in heart muscle. In this study there was no significant response of muscle to turpentine injection. 4. Two hours of parenteral nutrition increased fractional synthesis rates in all tissues when compared with Ringer's lactate. Somewhat larger responses to feeding were observed as a result of either interleukin-1 beta or turpentine injection in all tissues, but these improvements were not significant. 5. We conclude that the response of protein synthesis rates in liver and skeletal muscle to parenteral nutrition is not inhibited, and may be somewhat enhanced, during acute inflammatory conditions in the growing rat.

Acute-Phase Proteins↗
PubMed1993

Virologic markers of human immunodeficiency virus type 1 in cerebrospinal fluid. The HIV Neurobehavioral Research Center Group.

As part of a longitudinal study, 265 cerebrospinal fluid (CSF) specimens from 204 human immunodeficiency virus type 1 (HIV-1)-seropositive subjects and 43 seronegative controls were evaluated. Of the 204 seropositive persons, 78 (38%) had > or = 1 CSF culture positive for HIV-1; the probability of being culture positive increased as the number of CSF samples obtained increased (P = .0018). Significantly correlated with culture positivity were elevations in CSF protein level (P = .014) and CSF white blood cell count (P = .001). Virus was more readily cultured from clarified CSF (89%, 42/47) than from the cellular fraction (30%, 14/47; P < .00001). Amplification of HIV-1 DNA by polymerase chain reaction (PCR) from 25 seropositive persons was positive in 9 (82%) of 11 culture-positive and in 4 (29%) of 14 culture-negative specimens, while amplification of viral RNA detected all 11 culture-positive and 9 (64%) of the 14 culture-negative CSF specimens. These data support the hypothesis that the development of HIV-1-associated neurocognitive disorders are not dependent solely on the presence of HIV-1 within the central nervous system.

Adult↗
PubMed1993

Identification of psychobiological stressors among HIV-positive women. HIV Neurobehavioral Research Center (HNRC) Group.

This research describes major stressors in the lives of women who have been infected with the human immunodeficiency virus (HIV). Thirty-one HIV antibody positive (HIV+) women infected primarily through heterosexual contact participated in a two hour semi-structured interview detailing the circumstances, context, and consequences of all stressful life events and difficulties experienced within the preceding six months. Qualitative methods of data analyses were utilized (Miles & Huberman, 1984). HIV-related life events and difficulties were classified into primary and secondary stressors based on the stress process model (Pearlin et al., 1981). Problems arising directly from one's seropositivity were defined as primary stressors. Stressful life events and difficulties occurring in other role areas were defined as secondary stressors. Six categories of HIV-related stressors were identified and quantified. Primary stressors were health-related, and included both gynecological problems (e.g., amenorrhea) and general symptoms of HIV infection (e.g., fatigue). Secondary stressors related to child and family (e.g., future guardianship of children), marital/partner relations (e.g., disclosure of HIV+ status), occupation (e.g., arranging time-off for medical appointments), economic problems (e.g., insurance "hassles"), and social network events (e.g., death of friends from AIDS). This research indicates that HIV-positive women are exposed to multiple stressors; some may be viewed as unique to women, whereas others may be considered common to both sexes. Identification of stressors has implications for the design of medical and psychiatric interventions for women.

Adult↗
PubMed1993

Effect of antiretroviral therapy on the cerebrospinal fluid of patients seropositive for the human immunodeficiency virus.

Elevated levels of beta 2-microglobulin and neopterin in cerebrospinal fluid (CSF) have been associated with neurologic complications of infection with the human immunodeficiency virus (HIV). The effect of zidovudine (ZDV) on these markers was assessed by studying the effect of ZDV treatment duration on CSF levels in a cohort of 145 HIV-positive men who were receiving ZDV. CSF beta 2-microglobulin and neopterin levels were significantly lower in those who had been taking ZDV for an intermediate period of time (46-365 days) than in those who had received ZDV either long term (> 365 days) or short term (1-45 days). CSF quinolinic acid levels were independent of duration of ZDV administration. A second CSF evaluation was available after 1 year for 54 HIV-positive men (19 of whom were also in the first cohort) and 11 HIV-negative controls. Patients who had started ZDV between lumbar punctures showed a significant decrease in CSF beta 2-microglobulin, but in those who had been receiving ZDV for > 1 year beta 2-microglobulin increased (p = 0.001). The effect was not observed with neopterin (p = 0.14). (Quinolinic acid levels were not studied longitudinally.) Finally, we observed that CSF levels of beta 2-microglobulin, neopterin, and quinolinic acid correlated strongly with each other in HIV-positive individuals (r = 0.7, p < 0.0001), even though ZDV might have different effects on these markers. In conclusion, we report that initiation of ZDV therapy is associated with a transient decrease in CSF levels of beta 2-microglobulin and neopterin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Functional status and well-being in a placebo-controlled trial of zidovudine in early symptomatic HIV infection.

To determine the effect of zidovudine on functional status and well-being in patients with early symptomatic human immunodeficiency virus (HIV) infection, 70 subjects in a randomized, placebo-controlled trial (ACTG Protocol 016) were observed for 1 year using a brief quality-of-life questionnaire. Thirty-four subjects were assigned to placebo and 36 subjects to zidovudine, 200 mg orally every 4 h (1,200 mg daily). Functional status and well-being were measured every 3 months using a 30-item self-administered questionnaire derived from health ratings from the Medical Outcomes Study. The mean changes from baseline for zidovudine versus placebo groups were compared using paired and two-sample t tests. Subjects receiving a placebo reported better quality of life compared to baseline than subjects receiving zidovudine at 24 weeks for all dimensions of well-being, including overall health, energy, mental health, health distress, pain, and quality of life. The difference between the two groups' changes from baseline for overall health was 11.5 points on a 100-point scale (p = 0.02), and 11.1 points for energy (0.002). There were no differences between changes from baseline along various dimensions of functional status (physical, social, role, and cognitive function). At 52 weeks both groups reported worse overall health than at baseline, and changes in scores were more similar for the two groups. Although zidovudine has previously been demonstrated to delay progression of disease for patients with mildly symptomatic HIV infection, early in treatment the net effect of a 1,200 mg daily dose of zidovudine may diminish patients' subjective well-being.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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↗