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Biomedical subjects

I Grant

Publications and source records attributed to I Grant.

At least 73 records · Page 4Linked to original sources
PubMed1999

Accelerated risk of hypertensive blood pressure recordings among Alzheimer caregivers.

The purpose of this study was to determine whether the stress of caregiving for the Alzheimer's disease (AD) patient accelerates the likelihood of exceeding hypertensive blood pressure (BP) criteria in periodic longitudinal home assessments. In this cohort study, participants consisted of spousal caregivers of AD patients (n = 144) and demographically equivalent non-caregiving controls (n = 47). Thirty percent of caregivers and 33% of controls were receiving antihypertensive treatment at study entry. Supine systolic and diastolic blood pressure (SBP and DBP) was assessed by semi-automated recordings taken in the home every 6 months for 2 to 6 years. Survival analyses (Cox proportional hazards models) were used to determine whether the hazard for developing hypertension (DBP>140, SBP>90) was greater in caregivers than in controls, and whether increased hazards were related to background characteristics or the extent of caregiving demands. Based on periodic 6-month assessments of BP over 6 years, the hazards of meeting criteria for borderline hypertension were greater for caregivers than for controls (Cox Proportional Hazards, chi2 [1, N = 174] = 4.86, p = 0.03). This difference remained statistically significant (p<0.05) after controlling for age, gender, education, socioeconomic status, body mass index, and use of antihypertensive medications. Increased risk of hypertension was not related to the extent of daily living assistance provided, patient problem behaviors, or caregiver distress. The chronic stress of caring for an AD spouse may have adverse effects on blood pressure; however, the mechanism for this relationship remains unclear.

Aged↗
PubMed1999

Effects of noradrenergic and serotonergic antidepressants on chronic low back pain intensity.

To understand the relative efficacy of noradrenergic and serotonergic antidepressants as analgesics in chronic back pain without depression, we conducted a randomized, double-blind, placebo-control head-to-head comparison of maprotiline (a norepinephrine reuptake blocker) and paroxetine (a serotonin reuptake blocker) in 103 patients with chronic low back pain. Of these 74 completed the trial; of the 29 who did not complete, 19 were withdrawn because of adverse effects. The intervention consisted of an 8-week course of maprotiline (up to 150 mg daily) or paroxetine (up to 30 mg daily) or an active placebo, diphenhydramine hydrochloride (up to 37.5 mg daily). Patients were excluded for current major depression. Reduction in pain intensity (Descriptor Differential Scale scores) was significantly greater for study completers randomized to maprotiline compared to placebo (P=0.023), and to paroxetine (P=0.013), with a reduction of pain by 45% compared to 27% on placebo and 26% on paroxetine. These results suggest that at standard dosages noradrenergic agents may provide more effective analgesia in back pain than do selective serotonergic reuptake inhibitors.

Adrenergic Uptake Inhibitors↗
PubMed1999

The interactive effects of age and length of abstinence on the recovery of neuropsychological functioning in chronic male alcoholics: a 2-year follow-up study.

UNLABELLED: To explore how age and length of abstinence affects neuropsychological (NP) recovery in chronic male alcoholics, we examined 97 recently detoxified alcoholics (RDA) who were abstinent a mean of 29.7 (SD = 9.4) days at their first evaluation, and again 2 years later, at which time 62 had resumed drinking (RES) and 35 had maintained interim abstinence (ITA). To separate practice effects from NP recovery, the NP performance of the RES and ITA groups were compared to age- and education-matched 29 long-term abstinent (LTA) alcoholics, abstinent a mean of 4.3 (SD = 3.5) years at initial testing, and 49 nonalcoholic controls (NAC). Sample mean age and education was 48.7 (SD = 8.8) and 13.9 (SD = 2.7) years, respectively. The RDA and LTA groups were also matched on years of alcoholic drinking [i.e., 17.2 (SD = 9.3) and 15.6 (SD = 8.7) years respectively]. Results of 14 NP tests were reduced to 6 NP abilities (i.e., attention learning, memory (recall), abstraction-cognitive flexibility, complex perceptual-motor integration and simple motor skills) that formed dependent variables in 4 groups x 2 ages (median split at 51.4 years classified participants as young and old) repeated measures MANOVA. RESULTS: (1) the ITA group improved on abstracting ability more than other groups (p = .009) (2) the RES group deteriorated on motor tests (p = .03); (3) all younger alcoholics exceeded practice effects on abstracting ability, while older RES participants deteriorated relative to ITA group (3-way interaction, p = .03); and (4) the LTA group was comparable in NP performance to the NAC group. In conclusion, the extent and features of NP recovery among alcoholics are related to age, length of abstinence, and interim drinking.

Adult↗
PubMed1999

Detecting significant change in neuropsychological test performance: a comparison of four models.

A major use of neuropsychological assessment is to measure changes in functioning over time; that is, to determine whether a difference in test performance indicates a real change in the individual or just chance variation. Using 7 illustrative test measures and retest data from 384 neurologically stable adults, this paper compares different methods of predicting retest scores, and of determining whether observed changes in performance are unusual. The methods include the Reliable Change Index, with and without correction for practice effect, and models based upon simple and multiple regression. For all test variables, the most powerful predictor of follow-up performance was initial performance. Adding demographic variables and overall neuropsychological competence at baseline significantly but slightly improved prediction of all follow-up scores. The simple Reliable Change Index without correction for practice performed least well, with high error rates and large prediction intervals (confidence intervals). Overall prediction accuracy was similar for the other three methods; however, different models produce large differences in predicted scores for some individuals, especially those with extremes of initial test performance, overall competency, or demographics. All 5 measures from the Halstead-Reitan Battery had residual (observed--predicted score) variability that increased with poorer initial performance. Two variables showed significant nonnormality in the distribution of residuals. For accurate prediction with smallest prediction--confidence intervals, we recommend multiple regression models with attention to differential variability and nonnormality of residuals.

Adolescent↗
PubMed1999

Extending the p-plot: heuristics for multiple testing. HNRC group.

In the problem of large-scale multiple testing the p-plot is a graphically based competitor to the notoriously weak Bonferroni method. The p-plot is less stringent and more revealing in that it gives a gauge of how many hypotheses are decidedly false. The method is elucidated and extended here: the bootstrap reveals bias and sampling error in the usual point estimates, a bootstrap-based confidence interval for the gauge is given, as well as two acceptably powerful blanket tests of significance. Guidelines for use are given, and interpretational pitfalls pointed out, in the discussion of a case study linking premortem neuropsychological and postmortem neuropathologic data in an HIV cohort study.

Humans↗
PubMed1999

The impact of HIV-related neuropsychological dysfunction on driving behavior. The HNRC Group.

HIV infection often results in neuropsychological (NP) impairment. In order to assess the impact that HIV-related NP deficits may have on automobile driving, we evaluated 68 HIV-seropositive drivers using an NP battery and two PC-based driving simulations. Thirty-two participants were classified as NP impaired; most (72%) evidenced only mild impairment, and none met criteria for HIV-associated dementia. After controlling for degree of immunosuppression and disease stage, NP-impaired participants failed a previously validated driving simulation at a much higher rate than cognitively intact participants [OR = 5.3, 95% CI (1.7, 17.0), p = .006]. Similarly, on a simulation of city driving, NP impaired participants were more likely to fail based upon the number of accidents [OR = 6.1, 95% CI (1.5, 24.6), p = .01]. Simulator performance was predicted by functioning in a number of NP domains, with NP tests accounting for 13-30% of the variance on the simulations. Although it would be premature to extrapolate these findings to impairment in on-the-road driving, they do argue for greater attention to the impact that even mild HIV-related NP deficits may have on driving skills.

AIDS Dementia Complex↗
PubMed1999

Assessing risk for violence among psychiatric patients: the HCR-20 violence risk assessment scheme and the Psychopathy Checklist: Screening Version.

This study evaluated the predictive validity of the HCR-20 (Historical, Clinical, and Risk Management) violence risk assessment scheme and the Psychopathy Checklist: Screening Version (PCL:SV). Files of 193 civilly committed patients were coded. Patients were followed up in the community for an average of 626 days. Receiver operating characteristic analyses with the HCR-20 yielded strong associations with violence (areas under curve [AUCs] = .76-.80). Persons scoring above the HCR-20 median were 6 to 13 times more likely to be violent than those scoring below the median. PCL:SV AUCs were more variable (.68-.79). Regression analyses revealed that the HCR-20 added incremental validity to the PCL:SV and that only HCR-20 subscales predicted violence. Implications for risk assessment research, and the clinical assessment and management of violence, are discussed.

Adult↗
PubMed1999

Further crossvalidation of regression-based neuropsychological norms with an update for the Boston Naming Test.

Regression-based norms for the Trail Making Test, Boston Naming Test, and Wisconsin Card Sorting Test, which we published in 1991 and 1993, have been criticized by Fastenau (1998) as having overcorrected for demographic influences in a sample of 63 older adults. We present data from new, independent participant samples that are consistent with expectations from the regression-based norms. We propose that Fastenau's findings in this instance resulted from the nonrepresentative nature of his relatively small sample, rather than from statistical deficiencies of regression based norms. Our currently published norms on one of the four tests considered here, the Boston Naming Test, are based upon a participant sample that was small and had inadequate representation of young adults. We address this by providing updated norms based on a much larger and more representative sample (N = 531).

Adult↗
PubMed1999

Responses in the absorptive phase in muscle and liver protein synthesis rates of growing rats.

The effect of time after beginning of a meal (30, 60, 90 and 120 min) on liver and gastrocnemius muscle protein synthesis was tested in growing male rats using the large dose technique, based on a 10 min exposure to [15N]phenylalanine. The fractional synthesis rate was estimated from the ratio between the atom percent excess of tissue protein-bound and free labelled phenylalanine. The latter was measured by gas chromatography mass spectrometry using the tertiary-butyldimethylsilyl amino acid derivatives. The protein-bound phenylalanine of gastrocnemius muscle was separated from the other amino acids using preparative amino acid chromatography and then oxidised to N2 in an automated carbon-nitrogen Roboprep (CN) combustion module attached to a continuous flow isotope ratio mass spectrometer (IRMS), with m/z ions 28 and 29 monitored. The protein-bound phenylalanine from liver was separated by a gas chromatograph attached to a sample preparation module and an isotope ratio mass spectrometer (GC C-IRMS), with again m/z ions of 28 and 29 monitored. The following results were obtained: the daily fractional protein synthesis rates (ks) in gastrocnemius muscle and liver were 13.9% and 65.6% respectively, in 12 h fasted 145 g rats. These ks increased within 30 min after ingestion of meal to 14.9% and 91.8% for muscle and liver, respectively, and remained at these values for the next 90 min (14.6% and 87.4% at 60 min, and 14.3% and 88.6% at 120 min after the beginning of feeding). It was concluded that measurement of protein synthesis rates characteristics for the absorptive phase can be undertaken in a period from thirty minutes to two hours after start of a meal, without significant changes in the ks values.

Amino Acids↗
PubMed1999

Incorporation of urea and ammonia nitrogen into ileal and fecal microbial proteins and plasma free amino acids in normal men and ileostomates.

BACKGROUND: The importance of urea nitrogen reutilization in the amino acid economy of the host remains to be clarified. OBJECTIVE: The objective was to explore the transfer of (15)N from orally administered [(15)N(2)]urea or (15)NH(4)Cl to plasma free and intestinal microbial amino acids. DESIGN: Six men received an L-amino acid diet (167 mg N*kg(-)(1)*d(-)(1); 186 kJ*kg(-)(1)*d(-)(1)) for 11 d each on 2 different occasions. For the last 6 d they ingested [(15)N(2)]urea or, in random order, (15)NH(4)Cl (3.45 mg (15)N*kg(-)(1)*d(-)(1)). On day 10, a 24-h tracer protocol (12 h fasted/12 h fed) was conducted with subjects receiving the (15)N tracer hourly. In a similar experiment, (15)NH(4)Cl (3.9 mg (15)N*kg(-)(1)*d(-)(1)) was given to 7 ileostomates. (15)N Enrichments of urinary urea and plasma free and fecal or ileal microbial protein amino acids were analyzed. RESULTS: (15)N Retention was significantly higher with (15)NH(4)Cl (47.7%; P < 0.01) than with [(15)N(2)]urea (29.6%). Plasma dispensable amino acids after the (15)NH(4)Cl tracer were enriched up to 20 times (0. 2-0.6 (15)N atom% excess) that achieved with [(15)N(2)]urea. The (15)N-labeling pattern of plasma, ileal, and fecal microbial amino acids (0.05-0.45 (15)N atom% excess) was similar. Appearance of microbial threonine in plasma was similar for normal subjects (0.14) and ileostomates (0.17). CONCLUSION: The fate of (15)N from urea and NH(4)Cl differs in terms of endogenous amino acid metabolism, but is similar in relation to microbial protein metabolism. Microbial threonine of normal and ileostomy subjects appears in the blood plasma but the net contribution to the body threonine economy cannot be estimated reliably from the present data.

Adult↗
PubMed1999

Self-perceived interpersonal competence in older schizophrenia patients: the role of patient characteristics and psychosocial factors.

OBJECTIVE: This study compared older schizophrenia patients with normal subjects in terms of their perceived interpersonal competence. METHOD: A total of 95 middle-aged and elderly schizophrenia patients and 85 age-matched normal subjects completed the Interpersonal Competence Questionnaire. RESULTS: Patients scored significantly lower than normal subjects on initiation, provision of emotional support, and conflict management. Severity of psychiatric symptoms and other patient characteristics were examined as predictors of interpersonal competence among patients. Negative symptoms were inversely related to interpersonal competence, whereas emotional support from others and a positive appraisal coping style both yielded positive associations. CONCLUSION: These findings suggest the need for clinical interventions designed to enhance the interpersonal skills of older schizophrenia patients, particularly those with marked negative symptoms.

Aged↗
PubMed1999

Cortical synaptic density is reduced in mild to moderate human immunodeficiency virus neurocognitive disorder. HNRC Group. HIV Neurobehavioral Research Center.

Dendritic and synaptic damage (without frank neuronal loss) may be seen in milder human immunodeficiency virus (HIV)-related cognitive disorders. Synapse volume estimates, performed by stereological methods, could enhance the ability to detect subtle neuronal changes that may accompany cognitive impairment in HIV infection. For the present study, synaptic density and neuronal number were assessed by combined stereology/confocal microscopy and these measures were then correlated with ante-mortem levels of cognitive performance in AIDS patients. Three-dimensional stereological measures showed a significant correlation between reduced synaptic density and poor neuropsychological performance. To evaluate the specificity of any observed associations, additional variables including viral burden, astrogliosis and number of calbindin-immunoreactive neurons were measured. Factor analysis of a set of neuropathological variables revealed two factors; one defined by synaptic density and volume fraction, calbindin pyramidal neuronal densities and viral burden; the second by astrocytosis and calbindin interneuron density. Only the first factor correlated significantly with neuropsychological functioning during life. It is concluded that a combination of factors including synaptic damage, specific neuronal loss and increasing viral load underlies HIV-associated cognitive impairment. As synaptic damage is potentially reversible, early diagnosis and treatment of mild cogntive disorders may improve functioning and prevent the progression of brain disease.

AIDS Dementia Complex↗
PubMed1999

Does an increase in sulcal or ventricular fluid predict where brain tissue is lost?

Quantitative volumes of cerebrospinal fluid (CSF) and brain tissue were measured on magnetic resonance images (MRIs) of 287 individuals from 5 diagnostic groups: Alzheimer's disease (AD), chronic alcoholics (ALC), individuals positive for human immunodeficiency virus (HIV), schizophrenia subjects (SZ), and normal comparison subjects (NC) older than 50 years of age. Within each group, mean volumes were calculated for ventricular CSF, cortical (sulcal) CSF, cortical gray matter, total white matter, basal ganglia gray matter, and thalamic gray matter. Correlations of CSF measures with brain tissue measures were determined, and multiple regression analyses were performed to try and predict volume of gray matter or white matter region from volume of CSF compartment. Results indicated the following: 1. Enlarged cortical fluid volume significantly predicts cortical gray matter deficits for subjects with AD and those who are ALC and SZ but not for subjects with HIV or NC. 2. Enlarged cortical fluid volume also significantly predicts white matter deficits in all five groups. 3. Enlarged ventricular fluid volume significantly predicts basal ganglia deficits in AD, HIV, and NC but not in SZ or ALC. 4. Enlarged ventricular volume has no predictive value for thalamic volume for any of the groups. This study supports the clinical practice of predicting brain tissue volume loss from CSF enlargement but not for all brain regions in all diagnoses.

Adult↗
PubMed1999

Availability of intestinal microbial lysine for whole body lysine homeostasis in human subjects.

We have investigated whether there is a net contribution of lysine synthesized de novo by the gastrointestinal microflora to lysine homeostasis in six adults. On two separate occasions an adequate diet was given for a total of 11 days, and a 24-h (12-h fast, 12-h fed) tracer protocol was performed on the last day, in which lysine turnover, oxidation, and splanchnic uptake were measured on the basis of intravenous and oral administration of L-[1-(13)C]lysine and L-[6,6-(2)H(2)]lysine, respectively. [(15)N(2)]urea or (15)NH(4)Cl was ingested daily over the last 6 days to label microbial protein. In addition, seven ileostomates were studied with (15)NH(4)Cl. [(15)N]lysine enrichment in fecal and ileal microbial protein, as precursor for microbial lysine absorption, and in plasma free lysine was measured by gas chromatography-combustion-isotope ratio mass spectrometry. Differences in plasma [(13)C]- and [(2)H(2)]lysine enrichments during the 12-h fed period were observed between the two (15)N tracer studies, although the reason is unclear, and possibly unrelated to the tracer form per se. In the normal adults, after (15)NH(4)Cl and [(15)N(2)]urea intake, respectively, lysine derived from fecal microbial protein accounted for 5 and 9% of the appearance rate of plasma lysine. With ileal microbial lysine enrichment, the contribution of microbial lysine to plasma lysine appearance was 44%. This amounts to a gross microbial lysine contribution to whole body plasma lysine turnover of between 11 and 130 mg. kg(-1). day(-1), depending on the [(15)N]lysine precursor used. However, insofar as microbial amino acid synthesis is accompanied by microbial breakdown of endogenous amino acids or their oxidation by intestinal tissues, this may not reflect a net increase in lysine absorption. Thus we cannot reliably estimate the quantitative contribution of microbial lysine to host lysine homeostasis with the present paradigm. However, the results confirm the significant presence of lysine of microbial origin in the plasma free lysine pool.

Adult↗
PubMed1999

Test-retest reliability and practice effects of expanded Halstead-Reitan Neuropsychological Test Battery.

Test-retest reliabilities and practice effects of a broad range of neuropsychological measures were examined in 384 normal or neurologically stable adults. Median test-retest interval was 11 months (range 3-16 months). The reliability estimates for most of the measures are reasonably good, ranging from .70 to low .90s. An exception is the relatively poor reliabilities of most memory measures. For all test measures, the value on initial testing is a strong determinant of the value on the second examination. Practice effects are seen on most measures. The magnitude of the practice effects, however, varies as a function of type of measure, test-retest interval, age, and overall competency level of the participant. This study provides several types of retest information that may be useful for future research and clinical work: comparative reliabilities of the various measures, estimate of error variability associated with each administration, standard deviation of the change, and comparative magnitude of practice effects on various tests.

Adult↗
PubMed1999

Neuropsychological impairment-associated visual field deficits in HIV infection. HNRC Group. HIV Neurobehavioral Research Center.

PURPOSE: To examine the relationship between loss in peripheral visual sensitivity and neuropsychological functioning in seropositive patients with human immunodeficiency virus (HIV) without infectious retinopathy. METHODS: Subjects carefully screened for retinal disease and well-matched across demographic and medical variables were grouped according to normal (perimetry-nl) versus abnormal (perimetry-abnl) performance on achromatic automated perimetry and short-wavelength automated perimetry, standard clinical ophthalmologic measures of visual function. All subjects completed a detailed neuropsychological test battery and were classified as impaired or unimpaired, globally and across eight neurocognitive domains. Subjects were also classified according to whether they met diagnostic criteria for minor cognitive/motor disorder (MCMD) or HIV-associated dementia (HAD). RESULTS: Visual field loss was associated with lower performance in the abstraction, perceptual-motor, learning, and motor domains. Significant group differences were also found on numerous individual neuropsychological tests. Based on clinical ratings, we found deficits in learning and motor functioning. No perimetry-nl subjects met criteria for MCMD or HAD, whereas 32% of perimetry-abnl subjects met diagnostic criteria for syndromic cognitive disorders (five MCMD and one HAD). In a subset of subjects who underwent a lumbar puncture, there was a trend for the perimetry-abnl group to have a higher concentration of beta2 microglobulin, a marker for central nervous system immune activation. CONCLUSIONS: These results suggest that in some HIV-infected people reduced visual function may be caused by nonretinal disease, and perimetry may present a sensitive measure of HIV-related brain dysfunction.

Adult↗
PubMed1998

Cerebrospinal fluid tau protein is not elevated in HIV-associated neurologic disease in humans. HIV Neurobehavioral Research Center Group (HNRC).

We measured the concentrations of the neuron-specific protein, tau, in the cerebrospinal fluid (CSF) of 32 neurologically characterized HIV-infected (HIVpos) subjects and nine matched seronegative (HIVneg) controls using a sensitive ELISA assay. Of 32 HIVpos subjects, nine had HIV-associated neurocognitive disorders, and nine had clinically diagnosed peripheral neuropathies. CSF tau levels in subjects with HIV-associated neurocognitive disorders were similar to those in HIVneg subjects (185 +/- 83 vs. 223 +/- 106 pg/ml; P = 57). CSF tau levels in HIVpos subjects with peripheral neuropathies did not differ from those without neuropathies (320 +/- 190 vs. 251 +/- 185; P = 23). In summary, CSF tau levels were not elevated in patients with HIV-associated neurologic disease.

AIDS Dementia Complex↗