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Biomedical subjects

R F Lewis

Publications and source records attributed to R F Lewis.

At least 19 recordsLinked to original sources
PubMed2001

Comparison of diameter and perimeter methods for tumor volume calculation.

PURPOSE: Lesion volume is often used as an end point in clinical trials of oncology therapy. We sought to compare the common method of using orthogonal diameters to estimate lesion volume (the diameter method) with a computer-assisted planimetric technique (the perimeter method). METHODS: Radiologists reviewed 825 magnetic resonance imaging studies from 219 patients with glioblastoma multiforme. Each study had lesion volume independently estimated via the diameter and perimeter methods. Cystic areas were subtracted out or excluded from the outlined lesion. Inter- and intrareader variability was measured by using multiple readings on 48 cases. Where serial studies were available in noncystic cases, a mock response analysis was used. RESULTS: The perimeter method had a reduced interreader and intrareader variability compared with the diameter method (using SD of differences): intrareader, 1.76 mL v 7.38 mL (P < .001); interreader, 2.51 mL v 9.07 mL (P < .001) for perimeter and diameter results, respectively. Of the 121 noncystic cases, 23 had serial data. In six (26.1%) of those 23, a classification difference occurred when the perimeter method was used versus the diameter method. CONCLUSION: Variability of measurements was reduced with the computer-assisted perimeter method compared with the diameter method, which suggests that changes in volume can be detected more accurately with the perimeter method. The differences between these techniques seem large enough to have an impact on grading the response to therapy.

Brain↗
PubMed2001

Cerebellar lesions impair context-dependent adaptation of reaching movements in primates.

To produce accurate movements when conditions change suddenly, the brain must be capable of learning multiple versions of a given motor task and must be able to access the appropriate program using sensory information linked to the context of the movement. The neural basis for context-dependent motor learning is uncertain, but the cerebellum is thought to play a fundamental role. In this study, we examined the effect of lesions of the dorsal vermal and paravermal cerebellar cortex on the adaptation of reaching movements produced by modified visual feedback and accessed with a visual cue. Two rhesus monkeys were trained to point to targets displayed on a video monitor while viewing monocularly with either eye. During the experimental sessions, visual information received by one eye (the "modified" eye) was displaced horizontally, while the information received by the other ("normal") eye remained unaltered. In the first set of experiments (noncontextual paradigm), the animals pointed to targets while viewing with the modified eye. This paradigm resulted in a gradual improvement in pointing accuracy when viewing with that eye, but also produced a shift in pointing responses of equivalent size when viewing with the normal eye. In the second set of experiments (contextual paradigm), the animals alternated six blocks of reaches while viewing monocularly with the modified eye with six blocks viewing with the normal eye. This paradigm improved the pointing accuracy when viewing with the modified eye, but produced only a small shift in pointing responses when viewing with the normal eye. After the dorsal vermal and paravermal cerebellar cortex were resected, no change occurred in the pattern of adaptation produced by the noncontextual paradigm. The contextual paradigm, however, no longer selectively adapted pointing responses for each eye, but rather produced a pointing shift of equivalent size when viewing with either eye. The results indicate that pointing responses can be differentially adapted for each viewing eye, which is a form of context-dependent motor learning. This capability was lost after focal lesions of the dorsal vermal and paravermal cerebellar cortex, suggesting that these regions of cerebellar cortex are required to learn or store multiple representations of a movement, or to retrieve the appropriate motor program in a given sensory context.

Adaptation, Physiological↗
PubMed2001

Oculomotor function in the rhesus monkey after deafferentation of the extraocular muscles.

The function of extraocular muscle proprioception in the control of eye movements remains uncertain. In this study, we examined the effect of bilateral proprioceptive deafferentation of the extraocular muscles on eye movements in two rhesus monkeys. Before and after deafferentation, we analyzed baseline ocular alignment, saccades, pursuit, and vestibular eye movements. We also examined visually mediated adaptation of ocular alignment, saccades, and pursuit. Deafferentation of the eye muscles did not affect baseline ocular motor control, either acutely or over a 5-week period of study. Furthermore, visually mediated adaptation of the eye movement subtypes was also unaffected by deafferentation. These results suggest that ocular proprioception in primates is not used in the immediate, on-line control of eye movements and does not interact with visual cues in the adaptive modification of ocular motor function. We conclude that the efferent command (efference copy) provides sufficient information about eye kinematics to the brain for accurate eye movement control in normal monkeys, and that this information is modified by visual feedback independently of proprioception. We hypothesize that proprioception may be used to calibrate the efference copy during development and in response to perturbations by signaling potential mismatches between eye movement information derived from the efferent command and the actual motion of the eye transduced by the proprioceptive organs.

Adaptation, Physiological↗
PubMed2001

Ocular motor dysfunction in Lesch-Nyhan disease.

Eye movements were assessed in 22 patients with varying degrees of hypoxanthine-guanine phosphoribosyltransferase deficiency. Ocular motility was clinically normal in seven patients with moderate enzyme deficiency but grossly abnormal in 15 patients with severe enzyme deficiency. In patients with severe deficiency, fixation was interrupted by frequent unwanted saccades toward minor visual distractions. Voluntary saccades were associated with an initial head movement and/or eyeblink in all of these patients. When head motion was prevented, voluntary saccades were often delayed and sometimes absent. In contrast, saccade speed, reflexive saccades, and other reflexive eye movements appeared clinically normal. Four patients with severe enzyme deficiency also experienced mild blepharospasm, and two had ocular tics. These disturbances of ocular motility are consistent with dysfunction of the basal ganglia or its connections with ocular motor centers in the prefrontal cortex or midbrain.

Adolescent↗
PubMed2000

Hypoperfusion of inferior frontal brain regions in abstinent alcoholics: a pilot SPECT study.

OBJECTIVE: This pilot study evaluated hypotheses concerning the relationship between cerebral hypoperfusion and residual deficits in the functioning of frontal brain systems in abstinent long-term alcoholics. METHOD: The participants (N = 22) were 10 healthy, abstinent alcoholics (9 men) and 12 age-equivalent nonalcoholic controls (10 men). Cerebral blood flow was observed through the use of regionally specific computer-derived quantitative analysis of single photon emission computed tomography (SPECT) perfusion images. Measures of alcohol use, abstinence and neuropsychological functioning were also obtained to relate to SPECT findings. RESULTS: A positive relationship was observed between perfusion levels in the left inferior frontal brain region and years of sobriety. Alcoholics with less than 4 years of sobriety had significantly reduced left inferior frontal perfusion compared with both nonalcoholic controls and alcoholics having longer periods of sobriety. CONCLUSIONS: The findings support the hypothesis that frontal brain abnormalities in alcoholics may subside with extended abstinence.

Adult↗
PubMed1999

Ocular motor abnormalities in ataxia telangiectasia.

Although abnormal eye movements are a prominent feature of ataxia telangiectasia, the characteristics of the oculomotor dysfunction in the disease have been reported only in small groups of patients. We have examined eye movements clinically in 56 patients with ataxia telangiectasia, and obtained electrooculographic recordings of eye movements in 33 subjects. Deficits were observed in the eye movement systems that stabilize images on the retina, including pursuit, gaze holding, convergence, vestibular and optokinetic slow phases, and cancellation of vestibular slow phases. Abnormalities in the systems that maintain fixation and shift gaze were also prominent, including abnormal reflexive and voluntary saccades (characterized by prolonged latency, hypometric amplitude, and the use of head movements to initiate gaze shifts), impaired fixation, and a reduction in vestibular and optokinetic quick phases. The abnormalities in image stabilization most likely result from dysfunction in the cerebellar flocculus and paraflocculus. The basis of the saccadic and fixation disturbance is less certain but may be the result of abnormal supranuclear control of the superior colliculus resulting from dysfunction in the cerebellar vermis or the basal ganglia.

Adolescent↗
PubMed1999

Disconjugate adaptation of saccades: contribution of binocular and monocular mechanisms.

We studied the effects of prism-induced disparity on static and intrasaccadic alignment in six normal human subjects. A ten diopter base-out prism, calling for convergence, was placed in front of the central field of the right eye, so that at the center the eye viewed through the prism; at left and right, outside the prism. During 15 min of training, subjects made repetitive saccades solely in the right field of vision (C-R-C sequence). This paradigm required relative divergence for centrifugal (C-R) saccades and relative convergence for centripetal (R-C) saccades, as well as increase of the amplitude for all saccades made by the right eye. We found that during training, all subjects incorporated the necessary change in alignment into the saccades. After training the resultant intrasaccadic disconjugacy persisted when tested during monocular viewing, indicating that motor learning had occurred. Subjects demonstrated increased divergence for C-R and increased convergence for R-C saccades, in accordance with the change acquired during adaptation to the prism. In addition, five subjects developed increased divergence for C-L saccades, for which they did not train. Smaller and less consistent divergence was also observed for L-C saccades. Changes in intrasaccadic alignment were accompanied by changes in the relative velocities of the two eyes' saccades and slowing of the peak velocities in both eyes during training. Static alignment showed a general tendency toward convergence that did not parallel the changes in the intrasaccadic alignment, suggesting that saccade adaptation is system-specific. The pattern of transfer of the intrasaccadic disconjugacy to saccades in the untrained field and the changes in the relative speeds of the two eyes cannot be explained by monocular adjustment of the saccades. Our results indicate that both a binocular mechanism--saccade-vergence interaction--and monocular adaptation contribute to disconjugate adaptation of saccades.

Adaptation, Psychological↗
PubMed1999

Reduced basal ganglia blood flow and volume in pre-symptomatic, gene-tested persons at-risk for Huntington's disease.

The aim of this study was to examine basal ganglia volumes and regional cerebral blood flow in asymptomatic subjects at-risk for Huntington's disease who had undergone genetic testing. We determined which measures were the best 'markers' for the presence of the mutation and for the onset of symptoms. Twenty subjects who were Huntington's disease gene mutation-positive and 24 Huntington's disease gene mutation-negative participants, all of whom had a parent with genetically confirmed Huntington's disease, and were therefore 50% at-risk for inheriting the Huntington's disease gene mutation, were included in the study. To evaluate basal ganglia structure and function, MRI and single photon emission computed tomography (SPECT) were used. Quantitative measures of regional volumes and relative measures of regional perfusion were calculated. SPECT and MRI scans were co-registered so that MRI anatomy could be used accurately to place SPECT regions. Estimated years-to-onset in the mutation-positive subjects was calculated based on a regression formula that included gene (CAG)(n) repeat length and parental age of onset. Changes in imaging measures in relation to estimated years-to-onset were assessed. The imaging measure that was most affected in mutation-positive subjects was putamen volume. This was also the measure that correlated most strongly with approaching onset. In subjects >/=7 years from estimated onset age, the putamen volume measures were similar to those of the mutation-negative subjects. However, in subjects </=6 years from estimated onset age, there were dramatic reductions in putamen volume, resulting in >90% discrimination from both the far-from-onset and the mutation-negative subjects. Caudate volume and bicaudate ratio also showed a significant decline in the close-to-onset subjects, although to a lesser degree than putamen volume reductions. Furthermore, SPECT basal ganglia perfusion deficits were observed in mutation-positive subjects. Imaging markers of neuropathological decline preceding clinical onset are important for assessing the effects of treatments aimed at slowing the course of Huntington's disease. The current study suggests that quantitative assessment of basal ganglia may provide a means to track early signs of decline in individuals with the Huntington's disease gene mutation prior to clinical onset.

Adult↗
PubMed1999

Group C streptococci isolated from throat swabs: a laboratory and clinical study.

AIMS: To determine the prevalence of beta haemolytic, Lancefield group C streptococci in throat swabs taken in routine clinical practice, and correlate the species identified with presenting clinical features. METHODS: One year, laboratory based prospective study, using a questionnaire to elicit clinical information. RESULTS: 4.4% of throat swabs yielded group C streptococci, of which 38% belonged to S equisimilis and 53% to S anginosus-milleri group (SAM). Pyrexia was more common in patients with S equisimilis, but other clinical features did not differ significantly between the two groups. No S zooepidemicus was isolated. CONCLUSIONS: Species identification of group C streptococci from throat swabs does not appear to be clinically useful in this patient population. However, the prevalence and spectrum of organisms is similar to that reported in N America, where studies suggest a possible role in some cases of severe pharyngitis. Observational studies such as this lack power to resolve the issue of pathogenicity, for which a placebo controlled trial of antibiotic treatment is ideally required.

Adolescent↗
PubMed1999

Proprioceptive and retinal afference modify postsaccadic ocular drift.

Drift of the eyes after saccades produces motion of images on the retina (retinal slip) that degrades visual acuity. In this study, we examined the contributions of proprioceptive and retinal afference to the suppression of postsaccadic drift induced by a unilateral ocular muscle paresis. Eye movements were recorded in three rhesus monkeys with a unilateral weakness of one vertical extraocular muscle before and after proprioceptive deafferentation of the paretic eye. Postsaccadic drift was examined in four visual states: monocular viewing with the normal eye (4-wk period); binocular viewing (2-wk period); binocular viewing with a disparity-reducing prism (2-wk period); and monocular viewing with the paretic eye (2-wk period). The muscle paresis produced vertical postsaccadic drift in the paretic eye, and this drift was suppressed in the binocular viewing condition even when the animals could not fuse. When the animals viewed binocularly with a disparity-reducing prism, the drift in the paretic eye was suppressed in two monkeys (with superior oblique pareses) but generally was enhanced in one animal (with a tenotomy of the inferior rectus). When drift movements were enhanced, they reduced the retinal disparity that was present at the end of the saccade. In the paretic-eye-viewing condition, postsaccadic drift was suppressed in the paretic eye and was induced in the normal eye. After deafferentation in the normal-eye-viewing state, there was a change in the vertical postsaccadic drift of the paretic eye. This change in drift was idiosyncratic and variably affected the amplitude and velocity of the postsaccadic drift movements of the paretic eye. Deafferentation of the paretic eye did not affect the postsaccadic drift of the normal eye nor did it impair visually mediated adaptation of postsaccadic drift. The results demonstrate several new findings concerning the roles of visual and proprioceptive afference in the control of postsaccadic drift: disconjugate adaptation of postsaccadic drift does not require binocular fusion; slow, postsaccadic drift movements that reduce retinal disparity but concurrently increase retinal slip can be induced in the binocular viewing state; postsaccadic drift is modified by proprioception from the extraocular muscles, but these modifications do not serve to minimize retinal slip or to correct errors in saccade amplitude; and visually mediated adaptation of postsaccadic drift does not require proprioceptive afference from the paretic eye.

Adaptation, Physiological↗
PubMed1999

Hypoperfusion of the cerebellum and aging effects on cerebral cortex blood flow in abstinent alcoholics: a SPECT study.

BACKGROUND: This study evaluated hypotheses concerning alcoholism, aging, and the relationship between cerebral hypoperfusion and residual deficits in the functioning of cerebellar and neocortical brain systems. METHODS: The participants were 10 healthy abstinent alcoholics (9 men, 1 woman) and 12 nonalcoholic controls (10 men, 2 women) ranging in age from 35 to 67 years. Cerebral blood flow was observed through the use of regionally specific computer-derived quantitative analysis of single photon emission computed tomography (SPECT) perfusion images. Cerebellar perfusion was measured and compared with cerebral cortex perfusion in age-equivalent subgroups of alcoholics and controls (under 55 years; 55 years and over). RESULTS: In abstinent alcoholics under age 55, cerebellar perfusion ratios were significantly reduced compared with the controls. In alcoholics and nonalcoholic controls 55 years old and older, this relationship was reversed, probably as a result of diminished cortical perfusion with aging in the alcoholics and of cerebellar decline in the controls. CONCLUSIONS: The findings support hypotheses that the residual effects of alcoholism include cerebellar brain abnormalities and that aging combined with long-term alcoholism leads to cerebral cortical decline.

Adult↗
PubMed1998

Functional magnetic resonance imaging of alprazolam-induced changes in humans with familial alcoholism.

This study sought to identify whether subjects with a family history (FH + ) of alcoholism had changes in regional cerebral blood volume (rCBV) after an alprazolam challenge which distinguished them from subjects without a family history (FH -) of alcoholism using functional MRI (fMRI). Twelve FH + and eight FH - subjects were challenged with 1 mg of alprazolam or placebo in a double-blind crossover design. FMRI scans were obtained at baseline, 1 and 2 h after the challenge using the dynamic susceptibility contrast method with gadolinium. Mood scales, the Tufts Addiction Research Center Inventory-Morphine Benzedrine Group Scale and the drug liking scale, were administered every 30 min to assess drug effects. Global analysis of CBV showed a treatment by time decrease on alprazolam relative to placebo, but no effect by family history. The FH + group showed rCBV decreases at 1 h in the left caudate and left inferior prefrontal region, while the FH - group showed rCBV decreases at 2 h in the right inferior prefrontal region and anterior cingulate in response to alprazolam relative to placebo. FH + subjects reported more mood enhancement with alprazolam. This fMRI technique detected global and regional CBV changes induced by alprazolam. The location and rate of alprazolam-induced rCBV changes differed between FH + and FH - subjects. These changes may be related to the increased mood enhancement found in subjects genetically predisposed to alcoholism.

Adult↗
PubMed1998

Efference copy provides the eye position information required for visually guided reaching.

The contribution of extraocular muscle (EOM) proprioception to the eye position signal used to transform retinotopic visual information to a craniotopic reference frame remains uncertain. In this study we examined the effects of unilateral and bilateral proprioceptive deafferentation of the EOMs on the accuracy of reaching movements directed to visual targets. No significant changes occurred in the mean accuracy (constant error) or variance (variable error) of pointing after unilateral or bilateral deafferentation. We concluded that in normal animals efference copy provides sufficient information about orbital eye position to code space in craniotopic coordinates.

Animals↗
PubMed1998

Dynamic susceptibility contrast MR imaging of regional cerebral blood volume in Alzheimer disease: a promising alternative to nuclear medicine.

BACKGROUND AND PURPOSE: The goal of our study was to evaluate the sensitivity and specificity for Alzheimer disease of semiquantitative dynamic susceptibility contrast (DSC) MR imaging as compared with results of qualitative single-photon emission computed tomography (SPECT) in the same patients and with previously published semiquantitative SPECT results. METHODS: Fifty subjects were studied: 19 patients with probable Alzheimer disease with moderate cognitive impairment, eight mildly impaired patients with possible or probable Alzheimer disease, 18 group-matched elderly healthy comparison subjects, and five elderly comparison patients with psychiatric diagnoses. Relative values of temporoparietal regional cerebral blood volume (rCBV) were measured as a percentage of cerebellar rCBV, and group classification was assessed with logistic regression. The DSC MR imaging results were compared with SPECT scans in these same subjects and with previously published semiquantitative SPECT data. RESULTS: Temporoparietal rCBV ratios were reduced 20% bilaterally in the patients with Alzheimer disease. Using left and right temporoparietal rCBV as index measures, sensitivity was 95% in moderately affected patients with Alzheimer disease and 88% in patients with mild cases. Specificity was 96% in healthy comparison subjects and in psychiatric comparison subjects. Sensitivity with DSC MR imaging was considerably better than with visual clinical readings of SPECT scans (74% in moderate and 50% in mild Alzheimer disease cases), and was similar to previous published SPECT temporoparietal measurements (90%). Specificity with SPECT was 100% visually and 87% based on previous temporoparietal measurements. CONCLUSIONS: DSC MR imaging of rCBV is promising as a safe, potentially lower-cost alternative to nuclear medicine imaging for the evaluation of patients with dementia.

Adult↗
PubMed1997

Predictive power of duplex ultrasonography in asymptomatic carotid disease.

BACKGROUND: Duplex ultrasonography is considered a valid measure of stenosis of the carotid arteries, but the prognostic value of repeated ultrasonographic examinations is unknown. OBJECTIVE: To determine the ability of serial ultrasonographic measurements to predict cerebrovascular events in patients with asymptomatic carotid disease. DESIGN: Secondary analysis of data from a natural history study of asymptomatic carotid disease. PATIENTS: Asymptomatic patients with cervical bruits. MEASUREMENTS: Duplex ultrasonography of the carotid arteries was done at study enrollment and biannually thereafter. Multivariable Cox proportional hazards models with fixed and time-dependent covariates were used for analysis. RESULTS: 61 transient ischemic attacks (TIAs) and 38 strokes occurred in 715 participants over a mean follow-up period of 3.2 years; 4 strokes were disabling, and no deaths from stroke occurred. Sixty percent of strokes occurred in persons who did not have severe stenosis. One fifth of participants had stenosis progression. Baseline carotid stenosis was a significant predictor of the outcome "TIA or stroke" (relative risk, 1.5 [95% CI, 1.2 to 1.7]) and retained its predictive ability for more than 3 years. Progression of stenosis to 80% or more significantly increased the risk for cerebrovascular events and death. The sensitivity and positive predictive value of progression as an independent predictor of TIA or stroke were low. CONCLUSION: Severe carotid stenosis is associated with a higher risk for cerebrovascular events, but the power of repeated ultrasonography to predict ischemic events is limited by low incidence rates and low rates of progression. The evidence does not support the routine use of serial ultrasonography to determine the risk for stroke in unselected patients with asymptomatic carotid disease.

Adult↗
PubMed1997

Dynamic susceptibility contrast magnetic resonance imaging in neuropsychiatry: present utility and future promise.

Dynamic susceptibility contrast magnetic resonance imaging (DSC MRI) provides a noninvasive means to create high resolution maps of the regional distribution of cerebral blood volume (CBV). Most DSC MRI studies conducted to date have focused on the evaluation of patients with cerebral neoplasms, ischemia or infarction, and epilepsy. However, preliminary work suggests that DSC MRI may also provide clinically important information for the evaluation of patients with neuropsychiatric disorders, especially dementia and schizophrenia. Additionally, with appropriate modification, DSC MRI may be used to reliably evaluate the effects of pharmacological challenges on cerebral hemodynamics. As pharmacotherapy is an important component in the treatment of a range of psychiatric disorders, the dynamic assessment of changes in cerebral perfusion associated with drug administration may ultimately lead to the development of "brain function tests" for a wide range of disorders.

Brain↗